Contents

CVS Revision - 1  1

CVS Revision - 2  9

CVS Revision - 3  13

CVS Revision - 4  18

CVS Revision - 5  22

RS Revision - 1  28

RS Revision - 2  38

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RS Revision - 3  49

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Rheumatology Revision - 1  57
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Rheumatology Revision - 2  66
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Rheumatology Revision - 3  76
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Rheumatology Revision - 4  80
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Haematology Revision - 1  89
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Haematology Revision - 2  95
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Haematology Revision - 3  102

Haematology Revision - 4  110

Endocrinology Revision - 1  118

Endocrinology Revision - 2  127

Endocrinology Revision - 3  134

Endocrinology Revision - 4  145

CNS Revision - 1  157

CNS Revision - 2  161

CNS Revision - 3  165

CNS Revision - 4  170

CNS Revision - 5  176

Nephrology Revision - 1  181

Nephrology Revision - 2  186

GIT Revision  191

Hepatology Revision  198

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 CVS Revision - 1 1

CVS REVISION - 1 ----- Active space -----

Aortic Valve Disorders : ↓ ↑ risk of stenosis

3 leaflets/cusps if
↑ ↑ risk of regurgitation
N Aortic valve 3 commissures
1 fibrous annulus
Aortic Stenosis (AS)  00:04:37

Pathophysiology :
Degeneration/calcification Aortic sclerosis Gradient + Aortic stenosis.
of aortic valve + • Young : Bicuspid valve (BAV).
Inflammation • Elderly : Degeneration &

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(a/w atherosclerosis)

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calcification.
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Features :
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• BAV Young patients : • Tricuspid valve : > 60 y/o.

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- NOTCH 1 defect.
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- Associated with aortopathies (Mandatory CT aortogram).

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Note Rheumatic etiology :

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• Uncommon for AS.

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15 - 20 y
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• Rheumatic fever + Valvulitis RHD (MS + MR > MS + AR > AR + AS. )

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©

(MR > MR + AR)

Hemodynamics :
• Aortic valve opens at the end of isovolumetric contraction.
• N gradient b/w LV & aorta is zero (LV = 120 mmHg, Aorta = 120 mmHg).
• AS : Valve does not open completely Gradient + ∝ Severity of disease.
Note : Gradient = Mean transvalvular pressure gradient (MTPG).
Severe AS : Given by 40/4/1 rule :
• MTPG > 40 mmHg (In sclerosis < 20 mmHg).
• Peak flow velocity > 4 m/s (Across valve).
• Surface area of valve < 1 cm2 (Normal : 3 - 4).
Compensatory mechanism : To maintain cardiac output.
Concentric LV hypertrophy ↑ LV mass + ↓ cavity size.

Mild/Moderate AS : Severe AS : Very severe AS :

Asymptomatic Symptomatic LV failure (Poor prognosis)

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 2 Medicine

----- Active space ----- Clinical Features :

Angina Syncope Dyspnea
Poor prognosis if untreated after 5 yrs 3 yrs 2 yrs
Angina :
• ↑ LV mass ↑ O2 demand. • Tachycardia ↓ perfusion time.
• ↓ capillary density (w.r.t. wall thickness). • Atherosclerosis.
Syncope : D/t LV outflow obstruction F ixed cardiac output state even when
↑ demand.
Dyspnea : D/t ↑ filling pressure (LVEDP).
↑ LVEDP ↑ LAP ↑ PCWP Fluid escapes into pulmonary interstitium.
Exacerbating factors :
A - Fib :
• Contribution of atria to cardiac output ↑ (25 40%).

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• Thus, A-fib is fatal in AS.

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Systemic HTN : gm
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• Masking of severe AS :
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↑ SBP ↑ Aortic pressure ↓ Gradient (Falsely low).

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• Thus, strict BP control needed.

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Diagnosis :
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1. Transthoracic Echo : To look for 40/4/1 rule.

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2. Angiogram : Mandatory (To rule out atherosclerosis).

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3. CT aortogram.
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4. Dobutamine stress echo : To differentiate b/w

LV failure d/t AS vs Mild AS with Pre - existing LV failure
Low flow low gradient.
Examination Findings :
Pulse : Slow rising pulse
Peak achieved late
• Severe AS : Pulsus tardus.
• Very severe AS : Pulsus parvus et tardus. Peak is not achieved
BP : D/t LVH Masks AS.
JVP : Only elevated in terminal patients (Not relevant).
Apex : Laterally displaced Heaving apex (High amplitude sustained apex).
Heart sounds :
• S1 : N (Ejection click Mistaken for loud S1).
• S2 (A2) Loud : BAV (Young).
Soft : Elderly (Calcified valve).
Reverse/paradoxical split (P2 A2) : Severe AS.
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 CVS Revision - 1 3

• S3 : N /Less than N filling of a N /More than N filling of a ----- Active space -----
OR
non - compliant dilated ventricle. hypercompliant ventricle.
Pathological : Physiological.
LV failure (Very severe AS).
d/t + Non - stenosed mitral valve (No MS).
• S4 : Specific to AS
healthy LA
Hypertrophied, non-dilated LV
contraction
(no MR, AR).
• Murmur :
- Harsh ejection systolic murmur with late systolic accentuation.
- Best heard in aortic area & sitting position.
- Mixed frequency Low freq : Loud Carotids.
High freq : Soft blowing, musical Apex (Gallavardin phenomenon).
Management :

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1. Aortic valve replacement (AVR) :

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a. Done in Severe AS. gm
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b. Bioprosthetic valves (No anticoagulation needed).

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c. Asymptomatic severe AS : Follow-up Gradient > 50mmHg OR Symptoms AVR.

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Note : AS has a risk of sudden cardiac death.

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2. Transcatheter Aortic Valve Implantation (TAVI) : If surgery is C/I.

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Not open surgery; no ICU stay.

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Aortic Regurgitation (AR) 00:34:33

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CHRONIC REGURGITATION
Etiology :
Root issue : vs Valve leaflet issue :
• Syphilis • Rheumatic cause
• Marfan’s syndrome • Quadricuspid valve
• Ehler Danlos syndrome • Takayasu arteritis
• Takayasu arteritis • Ankylosing spondylitis
• Behcet’s disease
• IgG4 related disease Specific
• Cogan’s syndrome
Pathophysiology :
Hemodynamics :
• N diastolic gradient between LV (10 mmHg) & aorta (80 mmHg) : 70 mmHg Favours regurgitation.
• No backleak d/t competent aortic valve.
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 4 Medicine

----- Active space ----- Exacerbating factors :

• Nocturnal angina : Bradycardia at night More filling Prolonged diastole
Angina ↓ Blood to coronary circulation ↑ Regurgitation
• Systemic HTN :↑ Aortic pressure ↑ Gradient ↑ Regurgitation.

Relieving factor : Exercise/NTG/Nitroprusside.

Vasodilatation ↓ Aortic pressure ↓ Gradient ↓ Regurgitation.

Compensatory mechanism : Eccentric hypertrophy with dilatation.

Clinical Features :
Mild/moderate AR :
• Asymptomatic (Since ejection fraction is ↑↑).
• Occasional palpitation.
• LVEDP & ESV (End systolic volume) is N .

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Severe AR :
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• LV failure (Ejection fraction is N to low).
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• LVEDP ↑↑: Dyspnea.

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• ESV ↑↑: S3 + ve.

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• ↑ SBP & ↓↓↓ DBP (Almost zero) Wide pulse pressure Hill’s sign :
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Lower limb BP
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exceeds upper limb

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BP by 20 mmHg.
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Examination Findings :
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Pulse : Rapid upstroke & downstroke.

+
1. Collapsing pulse : High volume Ill - sustained peak.
2. Bisferiens pulse Two peaks in systole.
(AR/AR + Mild AS/HCM)
Note : Pseudocollapsing pulse N volume+ Rapid upstroke/downstroke
(Seen in MR) + well sustained peak.
BP : Wide pulse pressure.
JVP : Changes only in terminal disease.
Apex : Hyperdynamic apex, down & out.
Heart Sounds :
• S1 : Soft S1 (Premature closure).
For S1 :
Delayed A2 Root issue : Loud S2. • Premature : Soft closure.
• S2 :
↑ Blood in LV + Leaflet issue : Soft S2. • Delayed : Loud closure.
• S3 : Heard in failure.
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 CVS Revision - 1 5

• S4 : Not heard. ----- Active space -----

• Murmur : EDM (End diastolic murmur).
- High pitched, soft blowing.
- Decrescendo.
- Austin - Flint murmur : Low pitched d/t displacement of anterior mitral leaflet.

Cole Cecil murmur : Radiates to axilla.

Management :
AVR :
• Done in symptomatic severe AR.
Ejection fraction ≤ 55 %.
• Asymptomatic patient with 55/50 rule
LV end systolic diameter > 50 mm.
ACUTE REGURGITATION
Presentations :
Acute pulmonary edema (D/t sudden ↑ LVEDP ↑PCWP) ± Cardiogenic shock.

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Causes :

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• Infective endocarditis. gm
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• Aortic dissection : Acute AR + chest pain.

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• Rupture of sinus of Valsalva : Acute AR + Right heart failure symptoms.

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- Immediate Mx : NTG/Nitroprusside.
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- Definitive Mx : AVR.
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Mitral Stenosis (MS) 00:52:28

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Mitral Valve :
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• 3D structure.
• Surface area : 4 - 6 cm2.
• Parts :
- Annulus. - Papillary muscles.
- Leaflets with commissures. - Adjacent LV myocardium.
- Chordae.
Types of MS :
1. Progressive MS : > 1.5 cm2
Asymptomatic
2. Severe MS : < 1.5 cm2
Symptomatic
3. Very severe MS : < 1 cm2
Etiopathogenesis :
Main etiology : Rheumatic origin.
Main pathology : Commissural fusion Fish mouth abnormality.
(15 - 20yrs) MS + MR (M/c).
ARF RHD
MS + AR.
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----- Active space ----- Hemodynamics & compensation :

• Normal : Ventricular filling is passive > active & occurs across an open valve.
• In MS :
- ↑ LAP at rest for ventricular filling.
- On exertion ↓ diastole time ↑↑ LAP for ventricular filling.
- Very severe MS : LV failure.
Dyspnea Moderate MS ↑PCWP
First symptom of : Severe MS
• AS : Angina Pulmonary hypertension ↑Pulmonary artery EDP
• AR : Palpitation • Dyspnea at rest
• MS : Dyspnea • RVH
on exertion • Hypertensive tricuspid regurgitation
Clinical Features :

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• Pulmonary hypertension related • Ortner’s syndrome :

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symptoms. D/t compression of RLN.
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• Pulmonary edema (In tachycardia). • Hoarseness of voice.
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• A - fib. • Dysphagia :
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• Hemoptysis : D/t pulmonary D/t compression of esophagus.

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capillary apoplexy.
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Examination Findings :
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Pulse : Normal. JVP : Elevated (D/t RVH).

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BP : Normal. Apex : Tapping apex (Loud, ill-sustained S1).

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Heart Sounds :
• S1 : Loud S1 ↑ Velocity of valve closure.
Downward position of leaflets (D/t inadequate LV filling).
Delayed closure.
• S2 : • S3, S4 : Not seen.
- Loud, palpable P2 d/t Pulmonary HTN. • Murmur :
- A2 - P2 widening : Pulmonary HTN with - Low pitched, mid
RV failure. diastolic (MDM).
• Opening snap (OS) : - Presystolic accentuation
- Seen in organic MS. (Absent in A - fib).
- D/t ↑ LAP.
- Severity of MS Long duration of murmur.
Short S2 - OS gap.

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 CVS Revision - 1 7

Management : ----- Active space -----

1. Pulmonary edema Control heart rate β - blockers
Verapamil/Diltiazem
2. Anticoagulation : Oral vitamin K antagonists
3. Surgery : Percutaneous mitral balloon valvotomy /commissurotomy
Upon failure : Mitral valve replacement.
(1st line for : Calcific MS +/ Mod/Severe MR/LA clot)
Dx : Trans esophageal echo

Mitral Regurgitation (MR) 01:10:38

Acute MR :
• D/t posteromedial papillary muscle rupture.
• Seen in inferior wall MI (RCA involvement).
Chronic MR :

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1° MR : 2° MR (Innocent bystander mechanism) :
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• RHD : MS + MR (m/c). MR LV dysfunction Annular dilatation.
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• MVP : Developed countries. begets

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LV remodelling 2° MR.
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• SLE/Rheumatoid arthritis. MR
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Pathogenesis :
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Hemodynamics : Reduction in afterload.

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Worsens with hypertension

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LV - LA gradient >>> LV - Aorta gradient. ( ↑ aortic pressure).

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(LA = 10mmHg; LV = 120mmHg; Aorta = 120mmHg).

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Relieved by Nitrates :
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Regurgitation into LA. Vasodialation ( ↓ pressure).

LVEDP N / LV ESV N / Ejection fraction N .
Compensation : Eccentric hypertrophy with dilatation of LV.
Clinical Features :
• Mild/Moderate MR : Palpitation/Asymptomatic.
• Severe MR : LV failure Ejection fraction N / ↓ ↓ + LVEDP/LVESV ↑ ↑.
Examinations Findings :
Pulse : Pseudocollapsing pulse. Pulse in LV failure :
BP : Normal. • Pulsus alternans
JVP: Normal. • Pulsus dicroticus
Apex : Hyperdynamic apex; displaced down & out.
Heart sounds :
• S1 : Soft S1 d/t Poor coaptation of leaflet.
↓ ↓ dp/dt of isovolumetric contraction.
• S2 : Early A2 + Normal P2 Wide split S2.
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 8 Medicine

----- Active space ----- • S3 : Heard (Even without failure).

• S4 : Not heard.
• Murmurs : Pansystolic murmur.
- High pitched.
- Soft blowing.
- Seen in the apex.
- Radiates to axilla.

Myxomatous Degeneration :
MVP ± MR.
MVP
Click & murmurs : Non ejection click
• Dynamic auscultation (Valsalva & standing).
• ↓↓LV cavity size ↓↓chordae stretch ↑↑Prolapse

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Click moves closer to S1 :
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Long duration murmur.
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• All murmurs ↓on dynamic auscultation except :

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- HCM : ↑ intensity.
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- MVP : ↑ duration.
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Management :
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• Symptomatic : Surgery (Repair fails Replacement).

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• Asymptomatic with 60/40 rule :

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- Ejection fraction ≤ 60%.

- LV End Systolic diameter ≥ 40mm.

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 CVS Revision - 2 9

CVS REVISION - 2 ----- Active space -----

Basics of Pulse  00:00:13

Features :
• Pressure wave. • Velocity : 5 m/s.
• Origin : Aorta. • Assesses LV contractile performance.
Pulse Wave :
1. Normal wave :
P P : Pressure wave
T T : Tidal wave (Aortic recoil)
DN DN : Dicrotic notch

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DW : Dicrotic wave (Reflected wave)

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Determined by : Peripheral resistance
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S1 S2
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2. Stiff/non-compliant vessels : Cushioning effect of vessels lost

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↑ Pulse wave velocity

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Augments the T wave (DW arrives early)

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↑ Central SBP (CSBP) : Best marker for target organ damage

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S1

Abnormalities of Pulse 00:04:43

Relative Bradycardia :
• Rate of heart rate rise is < 10 beats per 1°F rise in temperature.
• Causes :
- Non - infectious : Lymphoma, drug fever. Rare
- Infectious : Typhoid, brucella, Q-fever, dengue, leptospirosis, malaria.
Rhythm Abnormalities :
Irregularly irregular : A - fib.
Regularly irregular : Ventricular premature contractions (VPC).
Volume Abnormalities :
Low volume (↓ Stroke volume) High Volume (↑ Stroke Volume)
1. Hypokinetic : LV failure 1. Collapsing : AR
2. Pulsus tardus : Severe AS 2. Pseudocollapsing : MR
3. Pulsus parvus et tardus : Very severe AS
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 10 Medicine

----- Active space ----- Contour Abnormalities :

1. Pulsus bisferiens 2. Pulsus dicroticus 3. Pulsus alternans 4. Pulsus bigemini
Regular alternating Irregular alternate
1 peak in systole
2 peaks in systole high & low volume high & low volume
1 peak in diastole
pulse pulse
P>T
P<T P=T
1. 2.
LV systolic failure LV systolic failure VPC

HCM (With SAM) Severe AR ± Mild AS

SAM : Systolic anterior motion
Note : Brockenbrough sign ↓ Pulse volume post VPC (In HCM).
Variation with Respiration :

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Pulsus paradoxus/ Reverse pulsus paradoxus :
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Normalis Aggregans : • SBP ↑ses with inspiration.
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• SBP ↓ ses by > 10 mmHg on inspiration. • Causes :

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• Causes : a. Intermittent positive

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i. Cardiac tamponade (m/c). pressure ventilation (IPPV).

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ii. Constrictive pericarditis (1/3rd cases). b. HCM.

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iii. Hyperinflated lung.

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iv. SVC obstruction.

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v. Pulmonary embolism.
vi. RCM (Rare).

Jugular Venous Pulse 00:14:00

Features :
• Height of column of blood above the sternal angle at 45°.
Semi - recumbent position ≥ 3 cm H2O is elevated.
• Assess right heart filling IJV used (Directly reflects right atrial pressure).
• RAP = 5 cm + IJV (Normal = 8 cm H2O).
Causes of elevated JVP :
Pulseless elevation : SVC obstruction.
Pulsatile elevation :
1. Circulatory overload. 4. RV pathology (RVH).
2. Tricuspid valve pathology (TS/TR). 5. Pulmonary valve pathology (PS/PR).
3. Pulmonary artery pathology 6. Right atrial pathology.
(Pulm HTN/embolism)
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 CVS Revision - 2 11

JVP Waveform : ----- Active space -----

Waves Interpretation
a Rt Atrial contraction (Presystolic)
x
x, x’ Atrial relaxation
C Upward tricuspid bulge (Coincides with S1)
v Atrial filling (Coincides with S2) ‘
y Atrial emptying (70% of ventricular filling) Mitral valve closure Aortic valve closure

Abnormalities :
Abnormal wave Condition
1. Prominent Tricuspid valve obstruction/RVH/Pulm HTN
a wave 2. Giant/Cannon AVNRT/Junctional rhythm/Complete heart block/VT with AV dissociation
3. Absent A-fib/Hyperkalemia

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Prominent/Rapid Cardiac tamponade/RCM/Chronic constrictive pericarditis (CCP)
x descent

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Absent Tricuspid regurgitation (TR)/RV failure
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Diminished Hypovolemia
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v waves ↑ Vena cava pressure : CCP/RV failure

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Prominent
2nd route : ASD/TR (Lancisi sign)
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Prominent CCP
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Slow Tricuspid stenosis (TS)

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Kussmaul’s sign :
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• Inspiration ↑JVP.
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• Causes : CCP/RCM/TS/RV MI.

• Not seen in cardiac tamponade.
Abdominojugular reflex : > 3cm/ > 15s Impending right heart failure.

Heart Sounds 00:34:40

Low pitched heart sounds Low pitched murmurs

• S3 • MS
• S4 • TS
• Tumour plop • Austin Flint murmur
A. S1 :
• Cause : Closure of AV valves.
• Occurrence : Atrial contraction S1 Isovolumetric contraction.
• Loud S1 : MS.
• Soft S1 : AR, MR, Good filling of the heart.
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 12 Medicine

----- Active space ----- B. S2 :

• Split into A2 P2 : D|t hangout interval ∝ Pressure beyond valve.
(A2 : 30ms-1; P2 : 80ms-1) ∝ 1
Distensibility of vessel

A2 P2
• BAV - AS
Loud Pulm. HTN (Palpable P2)
• Root pathology
• Elderly AS
Soft Pulm. stenosis
• Valve pathology in AR

Wide variable split Wide fixed split Paradoxical split

• Early A2 / Delayed P2. • Split does not move with respiration. • Loud P2 A2
• Cause : MR. • Causes : RV failure, ASD. • Causes : AR, AS.
Note : MS Single loud P2.

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C. S3 :

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• Pathology : N /Less than normal filling of a non-compliant dilated ventricle.
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• Seen in :
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- AS/AR with failure.

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- MR with/without failure.
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D. S4 : Seen in AS.
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Added Diastolic Sounds :

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O P Time 3 4
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Early :
Mid Late
• Opening snap.
• Pericardial knock. S3 S4
• Tumour plop.
Systolic Clicks :
1. Ejection clicks :
- Aortic ejection click : BAV.
- Pulmonary ejection click (Does not ↑on inspiration).
2. Non - ejection click : MVP

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 CVS Revision - 3 13

CVS REVISION - 3 ----- Active space -----

Heart failure (HF) - Basics 00:00:20

Structural/functional impairment in the ability of the ventricles to pump out blood

or fill itself.
Types of HF :
a. HFrEF : Ejection fraction < 40%.
b. HFpEF : Ejection fraction > 50%.
c. HFmEF : Mid range ejection fraction (40-50%).
Stages of HF :

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A B C D

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Only risk factors eg : DM/HTN A + Structural abnormality B + Symptoms (Present/prior) Advanced heart disease
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NYHA Classification :
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I II III IV
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Symptoms on Symptoms on ordinary Symptoms on less than Symptoms at

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exertion activity ordinary activity rest

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NYHA : Only for angina, dyspnea & palpitation (Not syncope).

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Heart Failure (HF) - Symptoms 00:06:04

LV systolic failure ↑LVEDP ↑RVEDP

• Cachexia (TNF-α) • ↑LAP ↑PCWP Dyspnea • ↑Abdomino jugular
• ↓ Urine output (Cardio-renal syndrome) reflex
• Altered sensorium Orthopnea & PND Pulm. edema (Impending failure)
• Cold extremities • O/E : Rales, S4 • ↑ JVP (>3cm)
• O/E : Narrow pulse pressure, S3, • Ascites
cardiomegaly • Edema
• Hepatomegaly
Framingham’s Criteria (Major) :
1. Dyspnea. 5. JVP.
2. Acute pulmonary edema. 6. Abdominojugular reflex.
3. Rales. 7. Cardiomegaly.
4. S3.

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----- Active space ----- Dyspnea :

Due to ↑LVEDP ↑LAP ↑PCWP.
Bendopnea Trepopnea
• Dyspnea on bending forward • Dyspnea while lying on one side
• Advanced Lt & Rt HF • Pleural effusion (more on right side)
• A/w ↑JVP & ↑PCWP
Crepitations :

HF : COPD :
• Fine gravitational crepts • Non-gravitational
• Cold extremities • Warm extremities
Other Symptoms : Decompensation :
1. Angina : D/t ↑LV mass, LVOT, Factors precipitating acute HF :
Microvascular disease. 1. Non compliance (Diet/drugs).

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2. Palpitation : D/t cardiomegaly. 2. Infections (Eg : Infective endocarditis).

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3. Syncope : D/t LVOT obstruction. 3. Anemia.
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4. Arrhythmia (Eg : A-fib).
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4. Sinus tachycardia : ↑Mortality.

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5. MI.
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6. NSAIDs & β-blockers.

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Heart Failure (HF) - Management 00:16:18

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Investigations :
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2. ECHO : For ejection fraction.

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1. ECG :
©

- Low voltage in limb leads. 3. Cardiac MRI : Gold standard.

- High voltage in chest leads.
- Poor R-wave progression.
Treatment Guidelines - HFrEF :
Drugs used (Fantastic 4) : Note :
1. SNS blockers : β-blockers • HFpEF : Comorbidity Mx.
- Metoprolol. • HFrEF : Guideline based Mx.
- Carvedilol. Vicious cycle of HFrEF :
- Bisoprolol (Best : β1 selective). ↓Cardiac Neurohormonal
- Started at lowest dose. output compensation
- Patient should be dry (No edema). Heart failure
2. RAAS blockers : SNS +
ARNI > ACEi > ARBs Cardiac remodelling RAAS +
Natriuretic peptide +

AT - II inhibitor (Valsartan) + Neprilysin inhibitor (Sacubitril).

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 CVS Revision - 3 15

3. Mineralocorticoid receptor antagonist (MRA) : ----- Active space -----

- Spironolactone/eplerenone/finrenone. Mortality benefit
- S/E : Hyperkalemia, gynecomastia. β-blocker > ARNI > ACEi > ARB
> Hydralazine + Nitrate
4. SGLT2 antagonist : Dapagliflozin/Empagliflozin.
Hydralazine : Used in renal
Add on drugs : failure with HF.
• Diuretics : Symptomatic relief.
• Ivabradine : Used if HR > 70 bpm + β-blockers max dose.
- Inhibits funny currents.
- S/E : Visual field abnormalities.

Ventricular Dysfunction 00:29:32

Types :
Systolic dysfunction Diastolic dysfunction

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Pumping issue Filling issue

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LV defect RV > LV defect
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F/b diastolic dysfunction May have N systole
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Constrictive pathology : CCP

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Diastolic dysfunction seen in

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Restrictive pathology (More severe) : RCM

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Symptoms of Diastolic Dysfunction :

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1. ↑RVEDP ↑Pressure in Vena Cava Rt HF.

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↑RAP
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• Ascitis precox • ↑JVP

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• Edema • Hepatomegaly
2. Systole N ; chamber size N .
3. ECG : Low voltage complexes.
4. Kussmaul’s sign + : CCP, RCM, TS.

Acute Pericarditis 00:34:00

Causes : Post viral/uremia.

Clinical features : Chest pain.
ECG : D/d : MI
1. Global ST elevation (Except V1). 1. Localised ST elevation
2. Concave ST elevation. 2. Convex ST elevation
3. No reciprocal changes. 3. Reciprocal changes +
4. PR depression. 4. No PR depression

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 16 Medicine

----- Active space ----- CCP vs RCM 00:39:10

Chronic Constrictive Pericarditis Restrictive Cardiomyopathy

Multiple relapses :
Acute pericarditis
Stiff, hypertrophic,
non-compliant, non-dilated
Pathology Rock like pericardium :
ventricle
Rigid, calcific, thickened, fibrous
pericardium with adhesions
Diastolic dysfunction
1. Intercellular accumulation :
Amyloidosis (M/c)
2. Intracellular accumulation :
a. Hemochromatosis (Iron)

om
Causes Post viral > TB b. Fabry’s disease

l.c
ai
gm (Glycosphingolipids)
c. Pompe’s disease (Glycogen)
@
60

3. No accumulation :
23
ik

DM/Scleroderma
hv

• Rapid x-descent
rit

• X-descent is not prominent

|

• Rapid y-descent : Friedreich’s

w

• No y-descent
ro

JVP sign
ar

• No square root sign

M

• Square root sign +

©

↑On inspiration : Kussmaul’s sign

Elevation &
After 1/3rd of diastole
Equalisation Absent
(Pericardial knock + )
of pressures
• Cachexic & malnourished
patient
• S3 +
• Pulsus paradoxus (1/3rd of
• No pulses paradoxus
patients)
Other • No pericardial knock
• Pericardial knock +
features • ↓Transmyocardial filling
• Broadbent sign : Systolic
pressure
retraction of apex (11th/12th rib
indrawing)
ECG : low voltage complexes
Ix MRI (IOC) ECHO
Rx Pericardiectomy Medical management
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 CVS Revision - 3 17

Cardiac Tamponade 00:57:03 ----- Active space -----

Cause :
Post-traumatic Acute rise in intrapericardial pressure.

Features :
• Holodiastolic elevation & equalisation of pressures No filling.
• Small chambers.
• Diastolic dysfunction.

Clinical Features :
Hypotension
Obstructive shock :
• Hypotension.
• Shock. Beck’s
• Disproportionate dyspnea. triad

om
• Tachycardia. Muffled ↑JVP

l.c
heart sound
ai
gm
On Examination :
@

• JVP :
60
23

- Prominent x-descent (Coupled constraint : Heart acts as one chamber).

ik
hv

- No y-descent.
rit

- No square root sign.

|
w

• No pericardial knock.
ro
ar

• No Kussmaul’s sign.
M
©

• Pulsus paradoxus (Inspiration SBP decreases > 10 mmHg).

Management :
Investigations :
1. ECG : Electrical alternans (low voltage complexes).
2. ECHO.
Treatment : Emergency pericardiocentesis.

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 18

----- Active space ----- CVS REVISION - 4

Dilated Cardiomyopathy (DCM) 00:02:40

Pathology :
Large, dilated, thin walled LV Poor contractile Poor relaxation.

Clinical features :
1. Systolic failure : ↓ cardiac output.
• Cachectic (TNFα). • O/E : Narrow pulse pressure.
• Cold extremities. S3 + .
• Altered sensorium. Cardiomegaly.

om
• Renal failure (CRS).

l.c
2. Diastolic failure : Dyspnea (↑LVEDP
ai
↑PCWP).
gm
3. Right heart failure : ↑JVP, ascites, edema, hepatomegaly.
@
60
23

Etiology :
ik

1. Genetic : Autosomal dominant

hv

Truncated variant titin mutation (M/C).

rit

Myh7 (Myosin heavy chain 7) mutation.

|
w

2. Peripartum cardiomyopathy :
ro
ar

• Best prognosis.
M
©

• D/t antiangiogenic factors : SFLT 1.

• R/F :
- ↑Age. - HTN. - Multiple pregnancies.
3. Alcohol induced : 4. Drug induced : Anthracyclines
• Good prognosis. (Worst prognosis).
• A/w ACE polymorphisms. 5. Autoimmune :
• Precipitated by deficiency of : • Sarcoidosis.
a. Selenium : Keshan’s disease. • Hemochromatosis.
b. Thiamine.
c. Mg2+. 7. Acute post inflammatory DCM :
6. Endocrine : Myocarditis in the infection/post infection period.
• Pheochromocytoma. New onset HF :
• ↑↑Trop I.
• Thyrotoxicosis. • Hypotension.
• M/C/C : HHV6 > Chagas.
• Acromegaly. • Chest pain.
• Mx : Supportive.
• Tachycardia.

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 CVS Revision - 4 19

Investigations : ----- Active space -----

1. ECG : Triad Low voltage in limb leads.
High voltage in chest leads.
Poor R-wave progression.
2. Echo : Global LV hypokinesia.
3. Cardiac MRI : Ischemia vs infarct; ejection fraction (Gold std).
4. Angiography.

Restrictive Cardiomyopathy 00:14:30

Seen in amyloidosis of the heart.

1. Primary.
2. Secondary : No cardiac involvement.
3. Transthyretin induced :

om
a. Senile systemic (Wild type) : Elderly patient with carpal tunnel syndrome.

l.c
b. Familial amyloid polyneuropathy (Mutant) : Severe ANS symptoms +
ai
gm
Cardiac involvement.
@
60

Features :
23

1. Biatrial enlargement.
ik
hv

2. Biventricular hypertrophy. Cardiac MRI : IOC.

rit
|

3. Interatrial septal thickening. Glittering/sparkling myocardium Bad prognosis

w
ro

4. Low voltage complexes.

ar
M

ECG : Pseudo infarct pattern.

©

Takotsubo Cardiomyopathy 00:17:10

AKA s tress induced cardiomyopathy/neurogenic myocardial stunning/

transient apical ballooning.

Cause : Sympathetic overactivity M/C in middle aged females.

Features : ACS like presentation ST elevation.

↑Trop I (Not as high as ACS).
↑↑NT Pro BNP.
Angiography Normal coronary arteries.
Hypercontractile base.
Bulging apex.
Prognosis :
• Short term : Like MI.
• Long term : Good.
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 20 Medicine

----- Active space ----- Hypertrophic Cardiomyopathy 00:20:12

M/C genetic CVS disease.

• AD.
• Mutation : Myosin heavy chain > Myosin binding protein C.
Males = Females
Poorer prognosis (More progressive disease).
95-99% Stable course
1-5% Complications :
1. Progressive HF.
2. Arrhythmias (A-Fib).
3. Risk of sudden cardiac death.
D/D : Pompe’s disease.

Hypertrophy :

om
l.c
Concentric, inappropriate, asymmetrical hypertrophy.
ai
gm
LV thickness ≥ 15mm • No cause. Left side :
@
60

• No dilatation. Septum + Anterior wall >> Posterior wall.

23

↓cavity size
ik
hv
rit

↑LVEDP Obstruction in HCM

|
w

Clinical Features : • 1/3 : Fixed obstruction.

rd
ro

• 1/3rd : No obstruction.
ar

1. Dyspnea (M/C) : D/t diastolic dysfunction.

M

• 1/3rd : Dynamic obstruction

©

2. Angina with normal coronaries (2nd M/C) : (Depends on cavity size).

D/t microvascular dysfunction.
3. Systolic Anterior Motion (SAM) : SAM pathophysiology
• D/t asymmetrical septal hypertrophy. Septal hypertrophy
• Leads to 2˚ MR. LVOT obstruction
4. A-fib : D/t ↑LAP.
5. LVOT obstruction Angina ↑velocity of blood across obstruction
Syncope Anterior mitral leaflet sucked into septum
Dyspnea (Mid-late systole)
Note : Most patients are asymptomatic.
↑obstruction
Examination Findings :
Pulse : Pulsus bisferiens (P>T). S1 : Normal.
BP : Normal. S2 : Normal/reverse split.
JVP : Normal. S3 : ±
Apex : Double apex/triple apex. S4 : ±

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 CVS Revision - 4 21

Murmurs : ----- Active space -----

• Lower left sternal border Ejection systolic murmur (D/t SAM).
• Apex Pansystolic murmur (D/t 2˚ MR).
Biopsy : Myofibre disarray.

Dynamic auscultation : Factors affecting LVOT obstruction

• Intensity of murmur ∝ LVOT obstruction. ↑Preload ↑Force of contraction
• Valsalva, standing ↑Afterload (Amyl nitrate, isoproterenol)
(↓Preload and afterload) ↑cavity size ↓cavity size
- ↑Intensity of murmur in HCM.
- ↑Duration of murmur in MVP. ↓obstruction ↑obstruction
• Brockenbrough sign :
↓Post-VPC pulse volume in HCM (D/t SAM).

Note : MVP and HCM are exceptions. Valsalva/standing ↓ all other murmurs.

om
l.c
Treatment :
ai
gm
β-blocker (DOC) : 2mg/kg propranolol
@

If C/I
60
23
ik

Verapamil/diltiazem Max dose : 480 mg

hv

(Not combined with β-blocker) Fails

rit

QT prolongation.
Add Disopyramide S/E
|

Anticholinergic S/E.
w

Fails
ro

↓ejection fraction (5-10%).

ar
M

If Medical Mx fails
©

Sx : Septal myomectomy
Indications for ICD (Implantable cardioverter defibrillator) :
• Family h/o sudden cardiac death.
• H/o spontaneous sustained VT.

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 22

----- Active space ----- CVS REVISION - 5

Inferior Wall MI (IWMI)  00:00:35

Dominance of Coronary Circulation : aVL(-30˚)

Depends on supply of PIVA/PDA
Lead I
RCA LCx

Lead II1 Lead II

Right dominant (80%) Left dominant (20%) aVF
(120˚) (90˚) (60˚)
Arteries Supplying Inferior Wall :

om
l.c
Inferior wall leads
ai
RCA OR LCx gm
Note :
@
60

Proximal OR Distal 1. RVMI : V3r, V4r, V5r

23

2. PWMI : V7, V8, V9

ik
hv

Landmark : Acute marginal A. (Only branch supplying RV free wall)

rit
|
w

RCA Branches :
ro
ar

1. SA nodal branch
M

Anterior branches Block IWMI + RV-MI ± PWMI

2. Atrial branch
©

3. Acute marginal artery

4. AV nodal branch Posterior branch Block IWMI (No RVMI) ± PWMI.
LCx block : IWMI + PWMI.
Features of RCA block : 3. ↑JVP
1. Bradycardia : D/t SA nodal branch block, vagal stimulation.
2. Posteromedial papillary muscle rupture 2° MR.
RVMI
(Single blood supply RCA) Clear lungs Hypotension
Rx : Hydration
Occluded artery :
ST ↑ ST↓
RCA Lead III > II aVL > aVR
LCx Lead II > III aVR > aVL
IWMI : ST ↑in lead II, III, aVF
+
RVMI (Proximal RCA) : V1 ST ↑/Discordance with V2,V3,V4
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 CVS Revision - 5 23

Anterior Wall MI (AWMI) 00:09:37 ----- Active space -----

LCA LAD.
LCx.
Blood supply
Area ECG leads
(In order)
LAD (D1) or LCx High lateral wall I, aVL
LAD (S1) Septum V1 >> V2
LAD (D2) Anterior wall V2, V3, V4
LAD (D4) or LCx Lateral wall V5, V6
Note : D Diagonal ; S Septal

om
l.c
ai
gm
@
60
23
ik
hv
rit
|

Extensive antero high lateral MI (Above D1, S1, D2, D3) :

w
ro

• ST ↑in V2, V3, V4.

ar
M

• Reciprocal changes in II, III, aVF.

©

• V1 ST↑.
• ST↑ in I & aVL.

ACS Management 00:14:02

Acute Coronary Syndrome :

1 out of 5 :
Myocardial injury
1. Clinical evidence of ischemia
2. ECG evidence of ischemia
↑Cardiac troponin (> 99th percentile) + 3. Pathological Q-waves
&
4. Echo changes
Rise & fall of troponin
5. Angio changes

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 24 Medicine

----- Active space ----- ACS Protocol : First medical contact (Diagnosis in 10 min)
Golden hours : 6 hours.
24hr PCI capable catheter No PCI capability

PCI within 60 min PCI possible within 120 mins if

shifted
Medical Mx after Stabilising Pt :
1. Aspirin 300 mg.
No Yes
2. Clopidogrel 300 mg (600 mg for PCI) Thrombolysis
(If PCI planned : Ticagrelor/Prasugrel). Tenecteplase : 0.5 mg/kg bolus Shift
3. Statin 20-40 mg.
4. Anticoagulant 30 mg s/c (Before PCI). Repeat ECG (Within 60-90 mins)
5. ACEi & β-blockers (Within 24 hours).
6. Lifelong aspirin & statins. Resolution No resolution
7. Antiplatelet for 1 year.

om
PCI within 2-24 hours Rescue PCI

l.c
ai
Arrythmia
gm 00:19:43
@
60

Mechanisms of Arrhythmias :
23
ik

1. Abnormal enhanced automaticity : Focal/MAT; Junctional tachy; Ischemic VT;

hv

Digoxin toxicity.
rit
|

2. Triggered activity : Long QT syndromes; Catecholamine induced tachy.

w
ro

3. Re-entry : AVNRT; A. Fib; Brugada Sx; AVRT & A. Flutter; Scar VT.
ar
M

TYPES OF TACHYARRHYTHMIAS
©

Narrow QRS Slightly wide QRS Wide QRS

QRS interval < 0.12 seconds 0.12 - 0.16 seconds > 0.16 seconds
Above Bundle of His bifurcation + Bundle
Origin Above Bundle of His bifurcation Ventricles
branch block
• Atrial tachycardia • Polymorphic VT;
Examples • Junctional tachycardia - • Monomorphic VT;
• AVNRT, AVRT, A-fib, atrial flutter • Torsades de pointes

Narrow QRS Tachycardia :

Regular R-R interval Irregular R-R interval
1. AVNRT :
- No P-waves OR
- P wave after QRS complex with short RP & long PR interval.
1. Atrial fibrillation
2. AVRT : P wave after QRS complex with short RP (>80-100 ms)
2. Multifocal atrial tachycardia (MAT) :
& long PR interval
3 distinct P-wave morphology seen
3. Focal atrial tachycardia :
- Long RP, short PR interval (P before QRS).
- Abnormal P-wave.
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 CVS Revision - 5 25

----- Active space -----

Atrial tachycardia
Management :
1. AVNRT :
- Adenosine.

om
- COPD : Verapamil Fails Metoprolol.

l.c
ai
- Synchronized DC cardioversion. gm
@

2. Atrial Tacycardia Rate lowering agents

60

3. MAT (A/w COPD Rx with theophyline) (Verapamil, β-blockers )

23
ik
hv

Note : Indications for unsynchronized cardioversion Pulseless VT; V. Fib.;

rit

Polymorphic VT.
|
w
ro

Atrial Fibrillation :
ar
M

Features : Types :
©

1. Irregular R-R interval. 1. Paroxysmal : <7 days. Reverts spontaneously

2. Fibrillary waves. 2. Persistent : >7 days. OR With drugs
3. No identifiable P-wave. 3. Permanent : LA dilatation >4 cm

Cannot be reverted back to normal.

Complications : Thromboembolism.
Risk factors :
1. Age.
2. HTN.
3. Associations :
- Structural heart/lung disease.
- OSAS.
- Thyroid patients.
- Psoriasis.
4. Mitral stenosis, prosthetic valve : Valvular A-fib.
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 26 Medicine

----- Active space ----- Management :

Hemodynamically stable Hemodynamically unstable

Transthoracic Echo DC cardioversion (100J x 2)

LA dilated > 4cm LA N

(Structural heart disease)
> 48 hrs (Or) < 48 hrs
Rate control : CCB
unknown duration
Rhythm control :
TEE/Cardiac CT • Ibutilide
• Amiodarone
Clot +

om
(Structural heart disease)

l.c
ai
Anticoagulation X 3wks Rhythm control Anticoagulation X 4wks
gm
(Drugs > DC cardioversion)
@
60
23

Wide QRS Tachycardia :

ik
hv

1. Monomorphic Ventricular Tachycardia :

rit

• Sustained VT + rate >100/min.

|
w

• ≥3 VPC.
ro
ar

• Capture beat/fusion beat ± .

M
©

• Management :
Monomorphic VT

Unstable Stable :
1. Procainamide.
Synchronised DC cardioversion 2. Amiodarone (Structural heart disease).
(360J) 3. Lignocaine : Post MI.
2. Torsades de Pointes/Polymorphic VT :
- Polymorphic VT + QT prolongation.
- Precipitating factors :
a. Antiarrhythmics : Class Ia, Ic, Class III.
b. Terbinafine, macrolides.
c. Hypokalemia, hypocalcemia,
hypomagnesemia.
d. Hypothermia.
- Mx : Defibrillation (200J) + 2g MgSO4 I.V.
Polymorphic VT
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 CVS Revision - 5 27

Hyper/Hypokalemia 00:45:20 ----- Active space -----

Hyperkalemia :
Causes : ECG changes :
1. CKD/AKI (m/c). • Tall T-waves : 6-7 mEq/L.
2. Hypoaldosteronism. • ↓ST, ↑PR : 7-8 mEq/L.
3. Pseudohypoaldosteronism : RTA type • Wide QRS : 8-9 mEq/L.
IV. • Absent P-wave : >9 mEq/L.
4. Spironolactone. Mx : IV Calcium gluconate.

om
l.c
ai
gm
@
60
23

Hyperkalemia
ik
hv

Hypokalemia :
rit

ECG changes :
|
w

• Sagging ST segment.
ro
ar

• Prominent U-waves.
M
©

Management : IV KCl.

Hypokalemia

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 28

----- Active space ----- RS REVISION - 1

Weibel’s generation of airways :

First 16 : Upto terminal bronchiole Conducting zone.
23 airway generations
Last 7 :
• Respiratory bronchiole
• Alveolar ducts Respiratory zone /acinus
• Alveoli

Approach to Lung Diseases 00:02:47

om
CLASSIFICATION

l.c
ai
Diseases gm Pathophysiology
Chronic obstructive pulmonary Larger & smaller airways
@
60

disease (COPD) : + Parenchymal + Vascular

23
ik

1. Chronic bronchitis involvement.

hv
rit

2. Emphysema 1. Lung parenchyma involvement

|

3. Small airway disease Causes :

w
ro

(Airways < 2mm diameter). a. Type 2 RF

ar
M

b. Pulmonary hypertension
©

c. Cor pulmonale
2. Alveolar capillary membrane
Obstructive lung diseases
Type 1 RF
• Bronchial asthma (BA) : Pure
-
airway disease.
• Bronchiectasis
- Exception : Traction -
bronchiectasis
• Bronchiolitis -
• Cystic fibrosis -

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 RS Revision - 1 29

----- Active space -----

Diseases Pathophysiology
Stages :
• Early : Hypoxia Type 1 RF
Interstitial lung disease (ILD) :
• Diffuse lung parenchymal Pulmonary hypertension
Intraparenchymal
fibrosis • Late : Hypercarbia + hypoxia
• Oxygen diffusion affected ↑ parenchymal
damage
Type 3 RF
Restrictive
• Neuromuscular (NM) :
lung
- Myasthenia gravis
diseases
- Amyotrophic lateral

om
sclerosis (ALS)

l.c
ai
- Guillain-Barré Syndrome
gm
Extraparenchymal
(GBS)
@
60

• Chest wall :
23

- Kyphoscoliosis
ik
hv

- Ankylosing spondylitis
rit
|

- Obesity
w
ro

• Pulmonary hypertension
ar
M

Vascular lung diseases (PHTN)

©

• Pulmonary thromboembolism
Pneumonia Due to exudate
Diffuse alveolar hemorrhage
Due to blood
(DAH)
Filling disorder
Filling/ Acute respiratory distress
pleura syndrome/ARDS Due to fluid
related (Non-cardiogenic)
diseases Filling disorder +
Lung abscess/necrotizing
parenchymal
pneumonia
destruction
Pleural disorder Pleural effusion

Note :
Lung parenchyma Alveoli + alveolar interstitium + vascular interstitium.

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 30 Medicine

----- Active space ----- Respiratory Failure 00:18:32

Types :
Physiology Pa 02 Pa CO2 P(A-a)02 Examples
• Alveolar filling disorders :
- Pneumonia
- DAH
Diffusion
Type 1 ↓ Normal ↑ - ARDS
failure
• ILD
• Vascular disorders
• Emphysema
Pump : Neuromuscular disorders
Ventilatory chest wall issues
Type 2 ↓ ↑ Normal
failure Effector organ : Chronic bronchitis

om
l.c
Generator : Brainstem disorders
ai
gm
Combined
@

diffusion & • ILD (Type 1 Type 3)

60

Type 3 ↓ ↑ ↑
23

ventilatory • Type 2 Type 3 RF is rare

ik
hv

failure
rit
|
w

Spirometry
ro

00:21:17
ar
M

Standard Lung Volumes & Capacities :

©

Lung volumes Lung capacities

• Tidal volume : 500 mL • Inspiratory capacity = TV + IRV = 3500 ml
• Inspiratory reserve volume (IRV) : 3000 mL • Functional residual capacity (FRC)/Equilibrium/
• Expiratory reserve volume (ERV) : 1000 mL Relaxation Volume = RV + ERV = 1/2 FVC = 2200 mL
• Residual volume (RV) = 1200 mL • Forced vital capacity = TV + TRV + ERV = 4.5L
• Total lung capacity = TV + IRV + ERV + RV
(TLC) = 5-6 L
Note :
Total body plethysmography : Measures RV, FRC, TLC (Spirometer can’t measure
them).

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 RS Revision - 1 31

FEV1/Forced expiratory volume in I second : ----- Active space -----

Amount of FVC exhaled in 1st second.
• FVC = 5L
• FEV1 = 4L Normal values.

Volume (L)
• FEV1/FVC ≥ 80%

Time (Sec)
Lung Volumes in Lung Pathologies :
Elastic recoil pressure (ERP) :
• Obstructive lung disease :
- ↓ ERP (D/t loss of alveolar Hyperinflation Dynamic compression of
attachments) airways.

om
• Restrictive lung disease : ↑ ERP (D/t fibrosis) ↓ inflation of alveoli.

l.c
ai
gm
Interpretations in lung pathologies :
@
60
23

Obstructive lung diseases Restrictive lung diseases

Vascular lung
ik
hv

Hyperinflation Air trapping Intra

Extra parenchymal diseases
rit

phase phase Parenchymal

|
w

FEVI/FVC Normal to ↑ Normal

ro

↓↓ ↓↓
ar

FEVI ↓↓ ↓↓ Normal Normal

M
©

FVC Normal ↓↓ ↓↓ Normal

Normal
DLCO ↓ Normal ↓↓
Exception : Emphysema ↓↓
NM Chest
RV disorders wall
↑↑ ↑↑ ↓ Normal Normal Normal
TLC ↑↑ Normal ↓↓ ↓↓ Normal Normal
RV/TLC - - - ↑↑ Normal -

Note : DLCO helps with early diagnosis & prognosis of ILD.

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 32 Medicine

----- Active space ----- Smaller Airway Disease :

• FEV1/FVC : Normal
• Forced expiratory flow rate 25-75%
(FEF 25-75)/

Volume (L)
Maximal mid expiratory flow rate
(MMEFR) is used for diagnosis.

Time (Sec)

DLCO 00:45:30

• Measurement of lung’s ability to transfer gas (02) across alvelo-capillary

membrane.

om
• Normal value : 20-30 mL/min/mmHg or 70-140%.

l.c
ai
DLCO Measurement : gm
@

• Gas used : Carbon monoxide (C0).

60
23

- ↑↑ hemoglobin affinity.
ik
hv

- Diffusion limited gas.

rit

- Negligible amounts in blood.

|
w

• Technique : Single breath technique.

ro
ar
M

Note :
©

Alveolocapillary membrane (Diffusion occurs) :

• Components :
- Alveolar epithelium + Basement membrane.
- Interstitium
- Capillary endothelium + Basement membrane.
• Surface area : 70 m2.
• Thickness : 0.2 - 0.5 micrometre.

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 RS Revision - 1 33

Factors Affecting DLCO : ----- Active space -----

Factors :
Increased DLCO Decreased DLCO
• ↑ Blood volume : • Valsalva maneuver
- Supine position • Smoking (↑ carboxyhemoglobin)
- ↑ Cardiac output • High flow O2
- Congestive cardiac failure • Anemia
- Polycythemia
• ↓ PaO2 : High altitude
• Exercise & obesity
• Left to right shunts

Disorders with altered DLCO :

om
Diseases with ↑ DLCO Diseases with ↓ DLCO

l.c
• DAH : • Rheumatological disorders prone to ILD :
ai
gm
- Goodpasture’s disease - Rheumatoid arthritis (RA)
@
60

- Wegener granulomatosis - Scleroderma

23

- Microscopic polyangiitis - Mixed connective tissue disease

ik
hv

• Bronchial asthma (Normal/↑) - Dermatomyositis

rit

• Pulmonary vascular diseases :

|
w
ro

- P. Hypertension
ar
M

- P. Thromboembolism
©

• Bleomycin toxicity
• Emphysema

Pleural Fluid Analysis 01:00:42

Significance of Pleural Fluid :

Pleural fluid Detected by
≥50 mL Ultrasound
≥60-80 mL Chest X-ray lateral view
≥200 mL Chest X-ray PA view
≥300 mL Clinically

Note : Normal pleural fliud volume : 10-30 mL.

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 34 Medicine

----- Active space ----- PLEURAL EFFUSION

Exudative v/s Transudative Effusion :

Light’s criteria :
1. Pleural fluid protein/Serum protein ≥ 0.5.
2. Pleural fluid LDH/Serum LDH ≥ 0.6.
3. Pleural fluid LDH ≥ 2/3rd of upper limits of normal serum LDH.

Features :
Exudative effusion Transudative effusion
• Light’s criteria : Any 1 of 3
Diagnostic
• Pleural fluid protein > 2.9 g/dL Light’s criteria : All 3 absent
criteria
• Pleural fluid cholesterol ↑↑
• Pneumonia, TB • Congestive cardiac failure, SVC

om
• Drugs obstruction

l.c
• Malignancy • Cirrhosis, Nephrotic syndrome,
ai
gm
• Connective tissue disease Hypoalbuminemia, Budd Chiari
Causes
@

• Esophageal rupture syndrome

60
23

• Peritoneal dialysis
ik
hv

• Hypothyroidism
rit

• Urinothorax
|
w
ro

Drugs causing exudative effusion :

ar
M

• Nitrofurantoin.
©

• Dantrolene.
• Amiodarone. Note :
• Methysergide. Methotrexate causes :
• Bromocriptine. • Hypersensitivity pneumonitis (M/c).
• Tyrosine kinase inhibitors. • Effusion (very rare).

Diseases causing both exudative & transudative effusion :

• Chronic constrictive pericarditis.
• Pulmonary embolism.
• Pulmonary infarction.
• Acute pancreatitis.

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 RS Revision - 1 35

Components of Pleural Fluid : ----- Active space -----

Normal Empyema Rheumatoid arthritis

1700 cells/μL :
• Macrophages.
• 75% macrophages
Cells Neutrophils • Multinucleate giant cells
• 25% lymphocytes
(Tadpole)
• <1% mesothelial cells
LDH <50% of serum LDH >1000 U/L -
Protein 1-1.5g/2L - -
• <30g/dL (Pathognomic)
Glucose >60g/dL 30-60 g/dl
• Can be 30-60g/dl also
pH - <7.2 <7.2
In malignancy, glucose levels : 30-6o mg/dL.

om
Eosinophilic Effusion :

l.c
>10% eosinophils in pleural fluid.
ai
gm
@

Causes :
60

• Hemothorax/Pneumothorax.
23
ik

• Parasitic : Paragonimus westermani.

hv
rit

• Fungal : Coccidioidomycosis, histoplasmosis.

|
w

• Asbestosis, drugs.
ro
ar

• Eosinophilic granulomatosis with polyangiitis (EGPA).

M

• Pulmonary infarction.
©

Community Acquired Pneumonia A/W Pleural Effusion :

Pathophysiology Investigations
• LDH
Inflammation
Simple parapneumonic • Culture
Normal
effusion • Glucose
↑pleural membrane permeability
• pH
• LDH ↑↑
Complicated Simple parapneumonic effusion
• Culture +
parapneumonic + Bacterial invasion Fibrin
• Glucose ↓↓
effusion deposition + septation
• pH < 7.2

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 36 Medicine

----- Active space ----- Empyema :

Complicated parapneumonic effusion + macroscopic pus.
• Clinical features :
- Fever unresponsive to antibiotics (Even after 3 days).
- Pleuritic pain, tenderness.
- Tachycardia, clubbing.
• Treatment : Intercostal drainage (ICD).
Indications of ICD :
- Empyema (Absolute).
- Pleural fluid pH <7.2.
- Organism in culture.
- Loculated pleural effusion.
- Massive effusion.

om
l.c
Massive pleural effusion
ai
gm
@
60
23
ik
hv
rit
|
w
ro
ar
M
©

Radiograph : D sign on empyema/ Ultrasound : Septations in empyema

pregnant belly sign

CECT : Split pleura sign

Note : Split pleura sign : Differentiates empyema from necrotizing lung abscess.

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 RS Revision - 1 37

Pleural TB : ----- Active space -----

• Pleural TB Can progress within 5 yrs Pulmonary/Extrapulmonary TB.
• Pleural biopsy (Medical thoracoscopy/VATs guided) : Conclusive.
- Gene XPERT/CBNAAT/Pleural fluid ADA levels & culture : Inconclusive.

Adenosine deaminase (ADA) :

Pleural fluid ADA Interpretation

<40 U/L Not suggestive of TB
>70 U/L + Lymphocytes
Highly suggestive of TB
+ Exudative effusion
TB, lymphoma, empyema,
40 to 70 U/L
malignancy, brucellosis

Note :

om
• Mesothelial Cells : <5% in TB (Normal : < 1%).

l.c
ai
• Pleuritis ± effusion gm
Suggestive of connective tissue disorder (SLE, RA).
@
60

Chylous v/s Pseudochylous Pleural Effusion :

23
ik
hv

Pseudochylous
rit

Chylous pleural effusion

pleural effusion
|
w
ro

Cause Trauma RA/TB

ar
M

• Triglycerides : ↑
©

• Chylomicrons : +
Features • Milky lymphocytic exudative effusion Cholesterol crystals
• Normal glucose
• Low LDH

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 38

----- Active space ----- RS REVISION - 2

Pulmonary Thromboembolism  00:00:22

Sites of Thrombosis :
Deep veins :
• M/c : Femoral vein (Supra popliteal).
• In pregnancy : Pelvic veins.

Note : Deep veins of calf M/c site of deep vein thrombosis.

Causes :

om
Inherited : Factor V leiden mutation (M/c).

l.c
ai
gm
Acquired :
@

• Antiphospholipid antibody syndrome (M/c).

60
23

• Nephrotic syndrome (Urinary loss of antithrombin I11/Protein C/S).

ik
hv

• Post-orthopedic surgery.
rit

• Malignancy (Adenocarcinoma).
|
w

• COPD.
ro
ar
M

Types :
©

Massive Submassive Non-massive

Hypotension + - -
Right ventricle(RV) dilatation Rv dilatation + • Recurrent pneumonia
Markers of RV ischemia : • No RV dilatation/markers
Small left ventricle (LV) • NT pro BNP, Trop 1 :
- Both ↑ High risk
Features ↓ Cardiac output - One ↑ Low risk

Hypotension

Shock

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 RS Revision - 2 39

Clinical Presentation : ----- Active space -----

Symptoms : Signs :
• Unexplained dyspnea (M/c). • Tachycardia, S3, ↑ JVP
• Syncope. • Clear lung fields,
• Chest pain (Pleuritic). Tachypnea, ↓breath
• Cough with hemoptysis. sounds, rales.
• Sudden cardiac death.
Note :
Cor pulmonale : RV hypertrophy + Rv failure S3, ↑ JVP.
Investigations :
ABG :
• Hypoxemia.

om
• Respiratory alkalosis.

l.c
ai
• Widening of (A-0) oxygen gradient. gm
@
60

ECG :
23

• T inversion in VI to V4 Correlates with severity.

ik
hv

• S1Q3T3 : No sensitivity/specificity.
rit
|
w

Echo :
ro
ar

• Findings Right atrium & RV dilatation.

M
©

Septal push.
Small LV.
• To rule out cardiac tamponade.
• McConnell’s sign : Hypocontractile RV free wall + Hypercontractile apex.

Imaging :
• CT pulmonary angiography (CTPA) : IOC.
- Findings Clot.
Pulmonary artery dilatation.
RV dilatation.
- Polo mint sign : Thin rim of contrast around
Central filling defect d/t thrombus.

CXR : Long linear band of

atelectasis

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 40 Medicine

----- Active space -----

Polo mint sign CTPA : Saddle thrombus

Management :
Well’s score
Parameter Score
Clinical signs of DVT 3
Alternative diagnosis less likely than pulmonary embolism (PE) 3

om
Heart rate >100/min 1.5

l.c
Recent surgery/immobilization 1.5
ai
gm
Previous PE/DVT 1.5
@
60

Hemoptysis 1
23

Malignancy 1
ik
hv
rit

Management based on score :

|
w

Score
ro
ar
M
©

<4 >4

PE unlikely. PE likely
Based on

High risk Low risk

Do CTPA. Do D-Dimer
If +
Do CTPA.

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 RS Revision - 2 41

Treatment Algorithm : ----- Active space -----

Give anticoagulants Unfractionated heparin (UFH) : 80 u/kg.

OR
Based on risk Low molecular weight heparin (LMWH) : 1 mg/kg s/c.

Submassive low risk/ Massive/

Non-massive Submassive high risk
check for C/I to thrombolysis
Continue anticoagulation. - +

Thrombolysis : Embolectomy.
• Alteplase
100mg IV over 2 hours x 14 days
Continue anticoagulation

om
• Newer oral anticoagulants (NOAC) : Better.

l.c
• Warfarin.
ai
gm
If anticoagulation C/I : Inferior vena cava (IVC) filter.
@
60
23

Pulmonary Hypertension 00:19:28

ik
hv

Resting mean pulmonary artery pressure ≥20 mmHg.

rit
|
w

Types :
ro
ar
M
©

↑ Pulmonary vascular resistance (PVR) ↑ Left atrial pressure (LAP)

Type 2 : D/t cardiac

Type 1 : causes.
• Pulmonary artery hypertension (PAH).
• Plexiform arteriopathy.

Type 3 :
• Lung related causes.
• ILD.
• Chronic bronchitis.
Type 4 : Chronic thromboembolic pulmonary hypertension.
PVR :
• Change in pressure/flow. • PVR < 3 wood units : Type 2.
• Rt. heart pressure - Lt. heart pressure • PVR > 3 wood units : Types 1,3,4.
Cardiac output
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 42 Medicine

----- Active space ----- TYPE 1 : PAH

Causes :
• Idiopathic (M/c).
• Limited systemic sclerosis.
• Toxins : Rapeseed oil.
• Serotonergic substances : Fenfluramine.
• BMPR-2 mutation.
• Infections : HIV, Schistosomiasis.
• Portal hypertension.

Molecular Pathogenesis :
• ↑ Endothelin.
• ↓ Nitric oxide.
• ↓ Prostacyclin.

om
Clinical Presentation :

l.c
ai
Symptoms : gm
@

• Fatigue (M/c).
60

• Breathlessness.
23
ik

• Chest pain (D/t RV ischemia).

hv
rit
|

Signs :
w
ro

• Loud, palpable P2.

ar
M

• Parasternal heave.
©

• Pulsations : Epigastric & 2nd intercostal space.

• Murmurs
- Pansystolic (Secondary to PAH) : Hypertensive tricuspid regurgitation.
- Early diastolic (D/t pulmonary regurgitation/artery dilatation) : Graham
Steell murmur.

Investigations :
Echo : PFT :
• Pulmonary artery dilatation. • FEVI/FVC : Normal.
• RV function. • FVC : Normal.
• Tricuspid regurgitation. • DLCO ↓.

Polysomnography & HRCT : To rule out obstructive sleep apnea & ILD.
V/Q scan : To rule out chronic thromboembolic PAH (Rx : Pulmonary endarterectomy).
6 minute walk test : Predictor of survival.

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 RS Revision - 2 43

Management : ----- Active space -----

Supportive care Specific therapy

• Avoid pregnancy • Calcium channel blockers
• Oral anticoagulants • Endothelin receptor antagonists (ERA)
• Long term oxygen therapy • Phosphodiesterase (PDE) 5 inhibitors
• Diuretics for right heart failure • Prostanoids
• Guanylyl cyclase stimulants
Rx is based on response to vasoreactivity test.
+ -

CCB : Nifedipine 240 mg Not responding to CCB Check NYHA class of symptoms

Class 1 to 3 symptoms Class 4 symptoms

om
Ambrisentan (ERA) + Prostanoids : Epoprostenol,

l.c
Tadalafil (PDE 5 inhibitor). Treprostinil.
ai
gm
If Medical Mx fails Sx Management Atrial septostomy.
@
60

Lung transplantation.
23
ik
hv

Interstitial Lung Diseases (ILD) 00:36:38

rit
|
w

• Diffuse parenchymal lung fibrosis.

ro
ar

• Mediators : TGF-β > PDGF.

M

• Inherited forms of ILD : Tuberous sclerosis, Neurofibromatosis.

©

Idiopathic Interstitial Pneumonia/ILD :

Types :
1. Idiopathic pulmonary fibrosis (IPF) :
- M/c.
- Usual interstitial pneumonia (UIP) : Histological counterpart.
- Males > Females.
- Poor prognosis : Pulmonary hypertension.
2. Non-specific interstitial pneumonia (NSIP).
3. Cryptogenic organising pneumonia (COP).
4. Respiratory bronchiolitis associated ILD (RB-ILD).
5. Desquamative interstitial pneumonia (DIP).
6. Diffuse alveolar damage (Histological counterpart) :
- Acute interstitial pneumonia (Covid).
- Poor prognosis.
7. Lymphocytic Interstitial pneumonia (LIP).
Medicine Revision • v4.0 • Marrow 8.0 • 2024
 44 Medicine

----- Active space ----- Note :

ILD a/w Smoking :
• RB-ILD. • DIP.
• Langerhans cell histiocytosis (LCH). • Rheumatoid arthritis associated ILD
(RA-ILD).

Patterns of ILD :
Pattern Seen in Onset Treatment
• Idiopathic : Majority Anti PDGF (Platelet
UIP • RA Chronic derived growth factor) :
• Males > Females Nintedanib
• Connective tissue diseases (CTD) Steroid + MMF
NSIP Subacute
• Drugs (Mycophenolate mofetil)
• Polymyositis

om
COP • Dermatomyositis Subacute Steroid + MMF

l.c
ai
• Anti-synthetase syndrome gm
@

• Sjogren’s Syndrome
60

LIP - -
• HIV
23
ik
hv

CTD a/w ILD :

rit
|

• Diffuse systemic sclerosis

w
ro

• Mixed connective tissue disease (MCTD)

ar
M

• Sjogren’s syndrome
©

• Polymyositis Lower lobe ILD.

• Dermatomyositis
• IgG4 related disease
• Ankylosing spondylitis (Upper lobe ILD).

Inherited causes of ILD :

• Tuberous sclerosis : A/w lymphangioleiomyomatosis.
• Neurofibromatosis.

Clinical Manifestations :
Signs : Symptoms :
• Clubbing. • Exertional dyspnea.
• Velcro crackles (Bilateral, Fine, End • Dry, non-productive cough.
inspiratory).
• Hypoventilation (Type 3 respiratory
failure).

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 RS Revision - 2 45

Investigations : ----- Active space -----

PFT :
• FEV1/FVC : ↑.
• DLCO : ↓.

Chest X-ray (CXR) :

B/L, Bibasal, Subpleural reticulonodular infiltrates.

HRCT: CXR : ILD

• IOC.
• Findings : Reticular & linear shadows.

Pattern HRCT findings

om
• Honey combing

l.c
• Cystic spaces
ai
UIP gm UIP : Honey combing
• Loss of lung architecture
@

• Traction bronchiectasis
60
23

NSIP Ground glass opacities (GGO)

ik
hv

• Consolidation
rit
|

COP • Reverse halo sign : GGO

w
ro

Surrounded by consolidation
ar
M

LIP NSIP + Nodules + Cysts

©

UIP : Honey combing

Note :
Halo sign : Consolidation surrounded
by GGO Invasive aspergillosis.

NSIP Pattern

COP : Reverse halo sign COP : Reverse halo sign

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 46 Medicine

----- Active space ----- Conditions Causing Cysts in Lungs :

1. Langerhan cell histiocytosis (LCH) :
• Young male smoker.
• Upper lobe ILD : Nodules + Cyst.
• A/w diabetes insipidus.
• Birbeck granules :
- CD1a cells ≥5%. LCH
- Tennis racquet appearance.
• Pneumothorax.
2. Lymphangioleiomyomatosis (LAM) :
• Young females with tuberous sclerosis.
3 LIP.

Causes of Upper Lobe ILD :

om
• Ankylosing spondylitis.

l.c
• Sarcoidosis. LAM

ai
gm
• Silicosis.
@
60

• Coal worker’s pneumoconiosis.

23

• ABPA : Allergic bronchopulmonary aspergillosis.

ik
hv

• Hypersensitivity pneumonitis.
rit
|

• Berylliosis.
w
ro

• TB.
ar
M

• LCH.
©

LIP
Drug Induced ILD :
• Amiodarone. • Mitomycin.
• Bleomycin. • Bromocriptine.
• Busulfan. • Methotrexate
Rare causes.
• Cyclophosphamide. • Anti-TNFα drugs

Note : Methotrexate causes hypersensitivity pneumonitis.

Occupational Lung Diseases 01:11:26

• Silicosis (M/c).
• Coal worker’s pneumoconiosis (CWP).
Complicated.
• Asbestosis.
• Berylliosis Uncomplicated.

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 RS Revision - 2 47

Silicosis : ----- Active space -----

Silicon dioxide/SiO2 (Quartz) :
• Industries : Rock/Slate cutting, blasting & mining.
Acute Silicosis Chronic silicosis
SiO2 exposure Large exposure within 2 years 10-30 years
Symptoms Dyspnea on exertion Dyspnea & cough
• PAS positive macrophages Affected cell : Pulmonary alveolar macrophage
• Milky white bronchoalveolar lavage (PAM) Reactivation of TB :
• CT : Crazy pavement pattern • Pleural involvement : Nil
(GGO + Nodules + Septation) • Parenchymal involvement :
- Upper lobe (UL) ILD
Findings Note : • Radiological findings :
Crazy pavement pattern is also seen in : - Angel wing sign
• Diffuse alveolar hemorrhage - Egg shell calcification (D/t Hilar
• Pulmonary alveolar proteinosis lymphadenopathy)

om
- Cavitation ±

l.c
• A/w Scleroderma

ai
Additional gm
Poor prognosis • Spirometry : Mixed Pattern
features
• Lung Signs in 25%
@
60
23

CWP :
ik
hv

Affected cell : PAM (No risk of TB reactivation).

rit
|

A/w autoimmune conditions :

w
ro

Caplan’s syndrome : RA + Active synovitis + Nodules + IgA rheumatoid factor + .

ar
M

Pleural involvement/Malignancy : Nil.

©

Parenchymal involvement :
• Nodules.
• Upper lobe fibrosis.
• Cavitation ±.
• No hilar lymphadenopathy/Egg shell calcification.
Berylliosis :
• Ceramic industry.
• D/D : Sarcoidosis.
Pleural involvement/Malignancy : Nil
Parenchymal involvement :
• Upper lobe infiltrates Fibrosis
• Non caseating granulomas
Features also seen in
• Thickening of bronchovascular bundles
sarcoidosis.
• Hilar adenopathy
• NSIP pattern.
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 48 Medicine

----- Active space ----- Asbestosis :

Two types of fibres Amphibole Crocidolite.
Serpentine (90%). Amosite (Most dangerous).
Duration of exposure : 10 years.

Pleural involvement :
• Unrelated to smoking. Pleural
• Manifestations : plaques
- Thickening Parietal pleura (M/c) :
• Pleural plaques + calcification.
• Holly leaf sign/Table mountain
sign/Candle drip sign.

Visceral pleura with lung

om
CXR : Pleural plaques

l.c
retraction : Crow feet’s sign.
ai
gm
- Benign asbestos related pleural effusion (Earliest).
@
60
23
ik

Exudative. Eosinophilic. Mesothelial cells.

hv
rit
|

Parenchymal involvement :
w
ro

• Lower lobe ILD : Diffuse massive fibrosis.

ar

Axial CT scan : Pleural plaques

M

• Infiltrates dyspnea.
©

• No lung signs.
• Spirometry : Restrictive pattern.
Malignancy :
Pleural mesothelioma Ca. lung
Smoking Unrelated Related
Duration of
30 years 10-30 years
exposure
Type Epithelioid (M/c) Adenocarcinoma
• Chest pain CXR : Holly leaf sign
Clinical features Cough with hemoptysis
• Mass detected
• Pan cytokeratin
Markers
• Calreticulin

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 RS Revision - 3 49

RS REVISION - 3 ----- Active space -----

Airway diseases :
• No parenchymal involvement.
• Type 1 respiratory failure (Normal PaCO2).

Eosinophilic Lung Disease 00:02:04

Types :
• BAL (Bronchoalveolar lavage) eosinophilia : > 25%.
• Lung tissue eosinophilia.
• Peripheral eosinophilia + lung infiltrates.
Causes :

om
l.c
Known : Unknown :
ai
• Parasite : • Eosinophilic granulomatous polyangitis (EGPA).
gm
@

- Loeffler’s syndrome : Hypersensitivity to • Acute eosinophilic pneumonia (AEP) :

60
23

ascaris. - ARDS like presentation.

ik

- Lung fluke invasion. - Quick recovery.

hv
rit

• Drugs : Nitrofurantoin. • Chronic eosinophilic pneumonia (CEP) :

|
w

• Tropical pulmonary eosinophilia (D/t - Reverse batwing appearance.

ro
ar

microfilaria). • Idiopathic hyper eosinophilic syndrome.

M

• Allergic bronchopulmonary aspergillosis

©

(ABPA).
Note :
• Conditions not under eosinophilic lung diseases :
- HSP (Hypersensitivity pneumonitis) in lung.
- Bronchial asthma (A/w eosinophilia).
- Pulmonary eosinophilic granuloma diseases.
• BAL eosinophilia with > 40% : CEP & Tropical pulmonary eosinophilia.

Aspergillus in Lung  00:06:56

Organism : Note :
• Aspergillus fumigatus. Aspergillus niger in ear infections.
• Saprophyte.
• Septate hyphae : Forms mucus plug.

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 50 Medicine

----- Active space ----- Manifestations of aspergillus infection :

1. ABPA.
2. Aspergilloma : Old tuberculosis cavity.
3. Chronic Cavitary Pulmonary Aspergillosis (CCPA) :
COPD patients : Thick walled cavities + bronchial wall invasion.
4. Invasive aspergillosis :
- Immunocompromised (Neutropenic patients)/steroid use.
- CT : Halo sign Consolidation surrounded by ground glass opacities.

ABPA
Pathophysiology :
A.fumigatus
Bronchial asthma/ colonization
Type 1 > Type 3 hypersensitivity.
Cystic Fibrosis (CF) patients

om
Clinical Manifestations :

l.c
• Fever.
ai
gm
• Cough with brownish thick mucus plugs :
@

Bronchiectasis : Proximal B/L symmetrical

60
23

central type.
ik
hv

• Fleeting infiltrates (Eosinophilic).

rit

• Crackles/clubbing (15% patients).

|
w

• Lung findings (20% patients).

ro
ar

CXR : Tram track lines

Rare : Converted to ILD (Upper lobe).
M
©

Investigations :
• IgE > 1000 (Obligatory criteria & follow up).
• Precipitin + .
• Eosinophilia > 500 (Supportive criteria).
Imaging :
CXR :
• Transient, irregular, parenchymal infiltrates. Finger in glove appearance
• Tram track appearance (Dilated airways).
• Finger in glove appearance :
D/t mucoid impaction in dilated airways.
CT : T
 ree in bud appearance
(Also seen in Sarcoidosis & TB).
Endobronchial involvement.

HRCT : Tree in bud appearance

(Central bronchiectasis)
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 RS Revision - 3 51

Treatment : ----- Active space -----

Steroids : Itraconazole : Omalizumab :

• DOC • In steroid non responders Monoclonal antibody
• For 12 weeks • For 16 weeks against IgE
HYPERSENSITIVITY PNEUMONITIS (HSP)
AKA Extrinsic allergic alveolitis.
Pathophysiology :
Repeated exposure to organic dust Type 4 > Type 3 hypersensitivity.

Involvement : Airways > Parenchyma

Features :
• IgE/eosinophils absent.
• Precipitin + .

om
• Non caseating granuloma.

l.c
ai
• Non - fleeting interstitial infiltrates (Parenchyma). gm
Systemic Symptoms : Nil.
@
60

Forms :
23
ik

• Subacute (M/C) : A/w response to steroids.

hv
rit

• Acute & chronic : Rare.

|

Imaging :
w

Mosaic/head cheese pattern

ro

HRCT : Mosaic/head cheese pattern (Various densities seen).

ar
M
©

Organic Dust Exposure :

Disease Exposure Antigen
Farmer's lung (M/C) Moldy hay
Thermophilic actinomycete (M/C) :
Bagassosis Moldy Sugarcane
Thermoactinomyces vulgaris
Mushroom worker's lung Moldy compost/mushroom
Malt worker's lung Barley
Tobacco worker's lung Mold on tobacco Aspergillus clavatus (2nd M/C)
Compost lung Compost
Wood worker's lung Wood pulp -
Other causes of organic dust exposure : Note :
• Bird fancier’s lung : Droppings of pigeon/parrots/chicken. HSP & ABA : Unrelated to smoking.
(Obstructive/emphysematous pattern)
• Chemical worker’s lung : Polyurethane foams (Isocyanates).
• Hot tube/humidifier/air conditioner lung : Cladosporium, MAC.
• Wood trimmer’s lung : Rhizopus.
• Familial HP/wood workers : Bacillus subtilis.
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 52 Medicine

----- Active space ----- Comparison with Differentials :

Asthma ABPA Extrinsic allergic alveolitis/HSP
• Colonization of airways • Interstitial lymphocytic
Pathology Hypertrophied mucus glands • Viscid mucoid impaction infiltration
• Tissue eosinophilia • Non caseating granuloma
Radiographic features :
• Migratory peripheral infiltrates
Diffuse alveolar interstitial
Early Normal hyperinflation • Atelectasis
infiltrates
• Bronchiectasis
Reticulonodular interstitial
Late Normal hyperinflation Fibrosis
opacities
Skin test reactions to aspergillus antigens :
Immediate + + +
Delayed - + +

om
Other findings :

l.c
ai
Peripheral
- + gm -
eosinophilia
@
60

IgG aspergillus
+ + +
23

precipitins
ik
hv

Serum IgE levels Normal/mildly elevated Marked elevation Normal

rit
|

Note : BAL lymphocytosis.

w
ro

• Sarcoidosis : CD4/CD8. >2:1

ar
M

• HSP : CD8/CD4.
©

Bronchiectasis 00:23:50

Obstructive type.
- Exception : Traction bronchiectasis Restrictive type.
Features :
Demographics : Females > males, 50-70 years.
Areas affected :
• Left lower lobe (M/c).
• Middle lobe : Mycobacterium avium complex (MAC).
• Right middle lobe : Brock’s syndrome (D/t lymph node in TB).
Pathological Changes :
1. Abnormal irreversible dilatation of bronchi :
D/t loss of smooth muscles & elastic tissue.
- Causes :
• Idiopathic (30%).
• Tuberculosis (40-50%), Measles & pertussis.
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 RS Revision - 3 53

• Genetic Alpha-1 antitrypsin deficiency . ----- Active space -----

Yellow nail syndrome, William Campbell syndrome.
- Types of dilatation :

Cylindrical (M/c) Cystic : Tubular Varicose

• Children
• A/w clubbing
2. Obliterative fibrosis of bronchioles :
Outer wall Loss of cilia

Cilia Increased mucus

Mucus

om
Destruction of walls

l.c
Mucous gland

ai
gm
Normal bronchus Bronchiectasis
@

Clinical Features :
60
23

• Chronic cough with mucopurulent (Foul smelling) sputum.

ik
hv

• Hemoptysis.
rit

• Early & mid inspiratory coarse crackles, diffuse rhonchi.

|
w
ro

Note : Dry bronchiectasis (Sicca) TB

ar
M

Imaging :
©

IOC : Volumetric multidetector helical CT scan/HRCT.

Findings :
• Airway dilatation : 1 - 1.5 times
adjacent vessel diameter Signet ring sign.
• Tram track sign.
• Tree in bud pattern.
Treatment : CT : Signet ring
• Airway clearance :
- Physiotherapy & postural drainage (Best).
- Nebulized 7% hypertonic saline/steam inhalation.
• Recombinant DNAse : For CF a/w bronchiectasis.
• Resection : Localized bronchiectasis + recurrent + unresponsive to drugs.
• Prophylaxis : Macrolides (Azithromycin) x 6 - 9 months.
Note : M/c organism causing infection in bronchiectasis : Pseudomonas.

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 54 Medicine

----- Active space ----- Chronic Obstructive Pulmonary Disease (COPD) 00:36:00

Types :
Chronic bronchitis (Clinical) : Cough with sputum x 3 months for 2 consecutive years.
Emphysema (Pathological) :
Airspace dilatation (Distal to terminal bronchiole) Followed by Destruction of walls
of airspaces.
Types of Emphysema :
Respiratory bronchioles
Alveolus
Terminal bronchioles

Alveolar duct
Normal acinus
Respiratory bronchiole Alveolar ducts and alveoli

om
Terminal bronchioles Alveolar duct Terminal bronchioles

l.c
Septum

ai
gm
Septum
@

Chronic inflammation
60

Respiratory bronchiole
23

and fibrosis Alveoli

ik

Centriacinar emphysema Paraseptal emphysema

hv
rit
|

Alveolar ducts and alveoli

w
ro

Alveolar duct Alveolus

ar

Terminal
M

Terminal bronchioles
bronchioles
©

Septum Septum

Respiratory Respiratory bronchiole

bronchiole
Panacinar emphysema Irregular emphysema

Centriacinar (M/C) Panacinar Paraseptal

Demographics Males Younger population Younger males
Smokers + - +
Areas of lung • Respiratory bronchiole • Complete involvement
-
involved • Upper lobe predominant • Lower lobe predominant
• α-1 antitrypsin deficiency Spontaneous
Associations -
• Liver disease pneumothorax

Note : α-1 antitrypsin phenotypes PiMM : Normal.

Pi�� : Severe deficiency.

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 RS Revision - 3 55

Features of Chronic Bronchitis & Emphysema : ----- Active space -----

Chronic Bronchitis Emphysema

• Parenchyma (more)
Structure involved Airway
• Vascular changes
• ↓PaO2 • ↓ PaO2
Gaseous changes
• ↑PaCO2 • Normal PaCO2
Type of respiratory failure Type 2 Type 1
Hypoxia More Less severe
Pulmonary hypertension/ Right ventricle failure/
More common Less common
Infections
Prognosis More mortality Better outcomes
Note :
Pulmonary hypertension : D/t ventilation perfusion mismatch Leads to Cor pulmonale.
Treatment :

om
Guidelines :

l.c
ai
gm
mMRC 0-1, CAT< 10 mMRC ≥ 2, CAT ≥ 10
@

0 to 1 moderate exacerbations (Not

60

Group A : Bronchodilators (Short acting) Group B : LABA + LAMA

23

leading to hospital admission)

ik

Group E :
hv

≥ 2 moderate exacerbations or ≥ 1 • LABA + LAMA

rit

leading to hospitalization
|

• LAMA + LABA ± ICS (If blood eos ≥ 300µL)

w
ro
ar

Key :
M

• LABA : Long acting beta agonist.

©

• LAMA : Long acting muscarinic antagonists.

• ICS : Inhaled Corticosteroids.
• mMRC : Modified medical research council dyspnea questionnaire.
• CAT : COPD assessment test.
• eos : Blood eosinophil count in cells per microliter.

Exacerbation : SABA + Short oral steroid therapy x 5-10 days.

Long Term Oxygen Therapy (LTOT) :
• Given for 14-18 hours/day after exacerbation.
• Indications :
- PaO2 < 55 mmHg.
- PaO2 55-60 mmHg (Pulmonary hypertension/RV failure).
Lobe resection : Localized emphysema (Limited cardiac problem, FEV > 20%).
Lung transplant : Severe cases.

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 56 Medicine

----- Active space ----- Pneumonia Management 00:53:36

CURB 65 Score :
C : Confusion. Interpretation :
U : Urea > 42 mg/dL. • Score 0, 1 : Outpatient management.
R : Respiratory rate > 30/min. • Score 2 : Inpatient management.
B : < 90/60 mm Hg. • Score 3 : ICU management.
65 : ≥ 65 years.

Management :
Inpatient :
• Severe (ICU) :
- Beta lactam + Macrolide.
OR
- Beta lactam + Levofloxacin.

om
• Non Severe :

l.c
ai
Beta lactam antibiotics gm
(Ampicillin-Sulbactam 1.5 - 3 g Q6h) Levofloxacin
@

OR
60

+ (75o mg OD)
23
ik

Macrolide (Azithral 500mg OD)

hv
rit

Outpatient :
|
w
ro

• Amoxicillin 1g TDS / Amoxyclav 625mg BD (If risk factors like diabetes + )

ar
M

+
©

Azithromycin 500mg OD / Doxycycline 100mg BD.

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 Rheumatology Revision - 1 57

RHEUMATOLOGY REVISION - 1 ----- Active space -----

Approach to Rheumatology 00:00:33

1. Intra-articular vs. Extra-articular Involvement :

Features Intra-articular Extra-articular
• Synovium • Ligaments
Structures involved • Articular cartilage • Tendons
• Intra-articular joint capsule • Muscles of fascia
• Diffuse, deep seated pain • Localised, superficial pain
Pain • Pain on active + passive motion • Pain on active motion
• Swelling/crepitus, deformity • Localised swelling, away from joint

om
Synovial involvement : Articular cartilage :

l.c
• Chronic (>6 weeks) inflammatory multi- • Osteoarthritis : Involves
ai
gm
system autoimmune CTD RA. the articular cartilage.
@
60

• Progression : Synovitis Synovial hypertrophy - Loss of joint space.

23

- Osteophytes.
ik
hv

Bone erosion Pannus - Subchondral sclerosis.

rit
|

• Non-inflammatory.
w
ro

Types of arthritis :
ar
M
©

Synovitis Spondyloarthritis (SpA) Crystal arthropathy

(Synovitis + Enthesitis+ Dactylitis) (Synovitis d/t crystal)
• Monosodium urate
monohydrate (MSUM)/Gout
• RA Axial SpA Peripheral predominant SpA • Calcium pyrophosphate
• SLE Ankylosing spondylitis • Psoriatic arthritis dihydrate (CPPD)/Pseudogout
• SLE like (Sjogren, (Sacroiliitis) • Reactive arthritis
polymyositis,
dermatomyositis)

2. Inflammatory vs Non-inflammatory :
a. Inflammatory :
M/c Rheumatoid arthritis (RA) > Sjogren’s syndrome.
b. Non-inflammatory :
Osteoarthritis (OA) : M/c non-inflammatory arthritis (M/c arthritis as a whole).

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 58 Medicine

----- Active space ----- ASSESSMENT PROTOCOL

Parameters RA findings (Symptoms >6 weeks)
1. Intra-articular v/s extra-articular Intra-articular (Sometimes has tenosynovitis)
2. Inflammatory v/s non-inflammatory Inflammatory (Signified by morning stiffness)
3. Unilateral v/s bilateral Bilateral
4. Symmetrical v/s asymmetrical Symmetrical
5. U/L vs L/L Upper limb
6. Mono/oligo/polyarthritis Polyarthritis
7. Small joint v/s large joint Small joint
8. Axial vs peripheral Peripheral
Note : SLE and SLE-like arthritis have a similar clinical picture.

JOINT INVOLVEMENT IN PATTERNS

om
Erosion :

l.c
ai
gm
@
60
23
ik
hv
rit

Erosions in RA Juxta-articular osteopenia in RA

|
w
ro

Causes of erosive arthritis : Causes of non-erosive arthritis :

ar

1. RA (M/c) Causes Deformity.

M

1. SLE/SLE-like arthritis
©

2. Psoriatic arthritis. 2. Acute rheumatic fever (Jaccoud’s

3. Chronic crystal arthritis (MSUM > arthropathy)
CPPD). 3. Acute crystal arthropathy
4. Multicentric reticulohistiocytosis. 4. Relapsing polychondritis (RPC)
Affects the pinna.
Note :
Erosions in SLE Rhupus (RA/SLE overlap).
MAGIC syndrome Mouth And Genital ulcers (Behçet’s) + Inflamed Cartilage
(RPC).
Jaccoud’s arthropathy :
• Non-erosive, deforming arthropathy.
• M/C d/t laxity of ligaments.
• Seen in acute RF, SLE, and SLE-like arthritis.

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 Rheumatology Revision - 1 59

Joints Involved and Spared : ----- Active space -----

RA :
• Involves : MCP + wrist + PIP + cervical spine.
• Spares : DIP (No synovium) + 1st CMC + 1st MTP + axial skeleton (Except C-spine).
Diseases involving DIP :
• Psoriatic arthritis (Also involves wrist, • Osteoarthritis (Spares wrist and
MCP, & PIP). MCP).
• Multicentric Reticulohistiocytosis • Juvenile Idiopathic Arthritis (JIA).
(MRH).
CLINICAL PATTERNS
1. Symmetrical Polyarthritis of Small Joints of U/L :

< 6 wks (Acute) > 6 wks (Chronic)

om
Post-viral Undifferentiated arthritis RA Psoriatic arthritis SLE & SLE-like arthritis

l.c
(DIP involved) (Non-erosive)
ai
Unless proved otherwise 1/3rd gm
(M/c Parvovirus B19) Progress to RA
@

2. Acute Monoarthritis :
60

1st joint
23
ik
hv

1st MTP (Coolest joint) Knee joint

rit
|
w

MSUM/Gout Septic arthritis > Crystal arthropathy (M/c CPPD)

ro
ar

3. Asymmetrical Oligoarthritis :
M
©

M/c joint involved Knee

Peripheral SpA

Reactive arthritis Psoriatic arthritis

Pathophysiology of RA 00:25:40

M/c multisystem inflammatory autoimmune CTD.

Progression :
1. Very early RA : < 3 months (Must be treated).
2. 3m-1y Early established RA.
3. 1-2 yrs Late established RA.
4. Chronic stabilized RA : >2 yrs (Starting Rx Not useful).
Epidemiology :
• Most common : 40-60 yrs old. • F : M = 3 : 1.

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 60 Medicine

----- Active space ----- Note :

• Rheumatological conditions with F:M = 9:1.
- Sjögren’s syndrome. - Fibromyalgia.
- SLE. - Chronic fatigue syndrome.
- Takayasu arteritis. - Primary biliary cirrhosis.
• Mixed connective tissue disease F:M = 15:1.

Factors :
A. Genetic factors :

HLA : Non-HLA :
1. HLA DR-B104 1. PADI-4
2. HLA DR-B114 Causative 2. PTPN 22
3. HLA DR-B101
4. HLA DR-B113 (Protective)

om
l.c
• HLA DRB104 :
ai
gm
- DR β chain hypervariable region QKRAA motif (Common to HLADRB114).
@
60

- ↑ risk by 5 times.
23

• PADI-4 :
ik
hv

- Responsible for post-translational modification (Arginine Citrulline).

rit
|

- Citrulline is an abnormal amino acid.

w
ro

B. Environmental factors :
ar
M

1. Smoking :
©

- Single most important environmental factor (Bad prognosis).

- ↑ risk for extra-articular manifestations (↑ 1LD).
- ↑ PADI-4 expression in airway ↑ abnormal protein modification.
2. Chronic periodontitis Etiology : Porphyromonas gingivitis.
Note :
• Smoking-associated ILD seen in
a. Desquamative interstitial pneumonia (DIP).
b. Langerhan’s cell histiocytosis (LCH).
c. Respiratory bronchiolitis associated ILD (RB-ILD).
d. ILD-RA.
• Alcohol & OCPs are mild protective factors for RA.
• Pregnancy is a protective factor (↑ IL-10 production Anti-inflammatory).

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 Rheumatology Revision - 1 61

Pathology : ----- Active space -----

Genetic factors Environmental factors

Abnormal protein modification :

a. Citrullination
b. Carbamoylation

Detected by
Antigen presenting cells Innate immune system
(Langerhan’s dendritic cells) (Neutrophils)
DC-T interaction
T-cells

B-cells

om
Migrate to joint

l.c
ai
Synovitis gm
@
60

Synovial hypertrophy Pannus formation Bone erosion

23
ik

Antibodies in RA
hv

00:44:00
rit
|

1. Anti-CCP Antibody :
w
ro

AKA Anti Citrullinated Polypeptide Antibody (ACPA)/MutatedCitrullinated Vimentin

ar
M

(MCV) antibody.
©

• Highly specific, + in majority cases.

• Best marker for pre-clinical infection.
• High titres Extra-articular manifestation.
2. Anti-CARP Antibody :
• Anti-carbamoylated peptide antibody.
• A/w palindromic rheumatism.
Note : Anti-PADI-4 antibody is also associated with RA.
3. Rheumatoid Factor :
• Less specific than anti-CCP (75-80%).
- + in other rheumatological conditions : Sjögren, cryoglobulinemia (2/3
cases), polyarticular JIA.
- Also seen IE, leprosy, PBC, parasitic infections, silicosis, sarcoidosis, HBV &
HCV.
• High titres ↑ disease activity.
• IgM antibody against Fc portion of IgG variable heavy chain 3 (IgGvH3).
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 62 Medicine

----- Active space ----- Note :

• Markers for relapse in RA ESR & CRP.
• Anti-CCP and RF are helpful in prognosis, but are of no use in relapse of RA.

Presentation in RA 00:48:52

CLINICAL PICTURE
A. Articular Manifestations and Progression :
Disease starts at the Distal Radio-Ulnar Joint (DRUJ).
Early changes (Reversible) :
Synovitis Zig-zag deformity

Synovial hypertrophy
(Type A > Type B synoviocytes)

om
l.c
Pannus formation

ai
Extra-articular changes : gm
Boutonniere deformity
Flexor tenosynovitis, bursitis
@
60

Articular changes : In order of appearance

23
ik

1. Radial deviation of wrist + ulnar deviation of MCP (Zigzag

hv

deformity).
rit

2. Subluxation of MCP joint.

|
w

3. Rupture of ulnar collateral ligament (Piano key styloid).

ro

4. Hitchhikers thumb deformity (Abduction + hyperextension).

ar
M
©

Irreversible changes :
1. Boutonnière’s deformity : Flexion of PIP + Hitchhiker’s thumb deformity
hyperextension of DIP.
2. Swan neck deformity : Hyperextension of PIP +
flexion of DIP.
3. Opera glass hand deformity: Arthritis mutilans.
(Complete destruction). Swan neck deformity
Other joints :
Joint affected Presentation/Deformity
Temporomandibular joint Mouth opening affected
C1-C2 joint Odontoid process affected Acute onset quadriparesis
Cricoarytenoid joint Change in voice
Lower limb : 5th MTP (m/c) Pes planus, forefoot varus, ankle valgus
Note : 1st MCP spared, and knee joint less commonly affected in RA.

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 Rheumatology Revision - 1 63

B. Extra-articular Manifestations : ----- Active space -----

M/c extra-articular manifestation Rheumatoid nodules (40%).
Rheumatoid nodules :
• ↑ risk :
- Smokers (+++).
- Anti-CCP/RF positive.
- Early onset and long duration disease.
• Site : Olecranon. Rheumatoid nodules
• Non-tender.
• Granulomatous reaction seen (Type IV hypersensitivity).
• Size ↓ on treatment.
PATTERNS OF PRESENTATION
1. Pre-clinical RA :
Presence of risk factors + autoantibodies + symptoms w/o clinical evidence of

om
l.c
arthritis.
ai
2. Chronic Symmetrical Polyarthritis : gm
@

• M/c presentation (60%). • Evidence of pain and inflammation in joints.

60
23

• > 6 weeks. • Small joints involved.

ik

Differentials :
hv
rit

• SLE & SLE-like disease Erosions - .

|
w

• Psoriatic arthritis DIP involvement + .

ro
ar

• CPPD/Pseudo RA Waxing & waning + , erosion - .

M
©

3. Palindromic Rheumatism :
• Intense, brief episodes of monoarticular arthritis.
• Sites : Knee and fingers.
• Attack Baseline (Intercritical period) 2nd attack (Similar to gout).
• Antibodies : Anti-CARP positive.
HEAD-TO-FOOT MANIFESTATIONS
1. CNS/Neuro-ocular :
a. C1-C2 myelopathy.
b. Synovial hypertrophy Entrapment neuropathy.
c. RA related small fibre peripheral neuropathy.
d. Brain parenchyma and thoracic/lumbar/sacral vertebra not involved.
2. Ocular :
a. M/c Keratoconjunctivitis sicca (Dry eye/20 Sjögren’s syndrome).
b. Episcleritis (> scleritis) : Correlates with disease activity.
c. Scleritis : Can cause painful loss of vision and scleromalacia perforans.
d. Uveitis is never seen.
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 64 Medicine

----- Active space ----- 3. Hematology :

a. Anemia of chronic disease (M/c anemia).
b. Total lymphocyte count Normal.
c. Thrombocytosis (2 ITP not seen).
0

d. Rapidly progressive anemia Autoimmune hemolytic anemia

(Warm Ab, IgG mediated).
e. ↑ risk of diffuse large B-cell lymphoma (DLBCL).
f. Large granular lymphocytes seen LGL leukemia (1% progresses to AML).
Felty syndrome : LGL Spectrum Felty’s
RA + neutropenia + splenomegaly.
• Seen late in the course of RA.
• RF and HLADRB104 positive.
• Seen in patients with nodules/deformities.
• Antibody against citrullinated histones + .

om
l.c
Large granular lymphocytes
4. Lung :
ai
gm
• Pleuritis ± effusion : Exudative, low sugars (<30mg/dL) and low pH effusion.
@
60

• ILD (M/c in smokers) Usual Interstitial Pneumonia (UIP) pattern : Severe

23

manifestation.
ik
hv

Caplan syndrome :
rit
|

• RA + nodules + Coal workers pneumoconiosis (CWP).

w
ro

• Seen with active synovitis.

ar
M

• RF +
©

5. Cardiovascular :
a. Vascular : UIP pattern
• Accelerated atherosclerosis MI (M/c cause of death).
• Immune complex mediated, small vessel lymphocytoclastic vasculitis (CV) with
purpura.
• Dangerous vasculitis forms (M/c males) :
i. Medium vessel vasculitis : Gangrene, mononeuritis multiplex.
Rx : Rituximab
ii. GI vasculitis : Intestinal infarcts.
b. Cardiac :
• Pericarditis w/o tamponade (Post-mortem finding).
• Mitral regurgitation (Similar to SLE).
6. Renal :
• 20 renal amyloidosis (M/c).
• Glomerular involvement (Membranous) : Very rare.

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 Rheumatology Revision - 1 65

7. Gastrointestinal : ----- Active space -----

GI vasculitis seen.
Note :Hypoandrogenism, osteoporosis, and pyoderma gangrenosum are also
associated with RA.

Treatment of RA 01:11:45

Drug classes :
DMARDS Biologics Small molecules
Anti-TNF α : Etanercept
Methotrexate
Anti-CD20 : Rituximab
Leflunomide
Anti-IL-1 : Anakinra JAK 1/3 - : Tofacitinib
Sulfasalazine
Anti-IL-6 : Tocilizumab JAK 1/2 - : Baricitinib
Hydroxychloroquine
CTLA-4/IgG : Abatacept
Therapy :

om
Methotrexate (Mtx) :

l.c
ai
• 1st line drug. gm
@

• 5 mg/week (2.5 mg + 2.5 mg). Dose may be increased to 25 mg/week.

60

• MOA in RA : ↑ in adenosine.
23
ik

• Monitoring :
hv
rit

- CBC (D/t bone marrow suppression).

|
w

- LFT (>4 times ↑ Stop MTX).

ro
ar

• Side effects :
M

- Mucositis (M/c).
©

- Hypersensitivity pneumonitis.
- ↑ nodule size.
- Dose dependant bone marrow suppression.
Other drugs :
• In absence of remission with MTX.
• Combination therapy :
i. Mtx + Sulfasalazine + HCQ (S/E : Bull’s eye maculopathy).
ii. Mtx + TNF-α - inhibitors (Best).
iii. Mtx + JAK (May be cardiotoxic).
Remission (Boolean based definition) :
Clinical assessment ≤1 + Tender joint count ≤1 + Swollen joint count ≤1 +CRP ≤1 mg/dL.

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 66

----- Active space ----- RHEUMATOLOGY REVISION - 2

Features of Systemic Lupus Erythematosus (SLE) 00:00:57

• F >> M.
• Childhood SLE : 100% renal involvement.
• Post menopausal SLE : Milder form (Renal sparing).
• M/c cause of death :
- 1st 5 yrs Infection > Lupus nephritis.
- After 5 - 10 yrs Accelerated atherosclerosis, MI.
• Male SLE : Severe, poor prognosis.
• Strong family history.

om
l.c
RISK FACTORS
ai
gm
Genetic :
@
60

HLA Non HLA

23
ik

• C1q deficiency (M/c) : Early complement deficiency

hv

• C2, C4 deficiency
rit

• TREX gene Chromosome 3

|

• HLA DR2
w

• Genes on X chromosome :↑ Risk with Klinefelter’s

ro

• HLA DR3
ar

syndrome
M
©

Environmental :
• Estrogen (Oral contraceptive pills).
• EBV.
• UV - B rays.

PATHOPHYSIOLOGY
Innate Plasmacytoid B cell activation :
Defective apoptotic/ Abundant
immune dendritic cell IL4 (Th2) Antibodies formed and
NETotic debris clearance IFN α T cell activation
system immune complex deposited
by neutrophils secreted (M/c : Th2)
activated (Type 3 Hypersensitivity)
Sites of Immune complex deposition :
• Vessel (Vasculitis).
• Synovium (Synovitis).
• Glomerulus (Glomerulonephritis).

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 Rheumatology Revision - 2 67

Anti Nuclear Antibodies (ANA) and ANA profile 00:08:44 ----- Active space -----

ANA :
• Screening test for multisystem connective tissue diseases.
• ANA +ve in :
- SLE : 97 % cases (3 % ANA -ve Anti Ro W-52/SS-A).
- Sjogren’s : 85 % cases (Least).
Note :
Conditions where 100 % ANA positive :
• Drug induced lupus erytheomatosus (DILE).
• Type 1 autoimmune hepatitis.
• Mixed connective tissue disease (MCTD).
Indirect Immunofluorescence (IF) :
• ANA done by IF using Hep 2 cell line.

om
• ≥ 1 : 80 Positive titre.

l.c
ai
Pattern Antibodies Specific diseases
gm
ds - DNA SLE
@
60

Homogenous
Anti histone DILE
23
ik

Dense fine
hv

Rule out CTD

rit

speckled
|
w

• SS - A
ro

Fine speckled Sjogren’s syndrome

ar

• SS - B
M
©

Coarse anti smith SLE

speckled anti U1 RNP MCTD

Nucleolar anti PM-SCL-70 Polymyositis - Scleroderma overlap syndrome

Cytoplasm anti Jo - 1 Polymyositis and Dermatomyositis

Note :
• Overlap syndrome :
- Features of > 1 CTD.
- CTD included : SLE, Sjogren (M/c), Polymyositis, Dermatomyositis,
Systemic sclerosis, RA.
• MCTD :
- Specific overlap along with +ve anti U1 RNP + 100 % +ve ANA and F >> M (15 : 1)
- A/w severe Raynaud’s phenomenon.

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 68 Medicine

----- Active space ----- ANA PROFILE (IMMUNOBLOT)

Done for ANA +ve/High suspicion cases.
Antibodies in SLE Significance
• Titres measured separately (by ELISA).
• A/w ↑ risk Nephritis, vasculitis.
Anti ds - DNA
• +ve in 75 % of cases.
• Assess disease activity in relapses.
• +ve in 25 % cases.
Anti Smith
• Most specific.
• Indicates 2˚ Sjogren’s.
• In pregnancy : A/w Neonatal Lupus + Complete
heart block.
Anti Ro/La • Better prognosis in SLE : ↓ Risk in Nephritis,

om
(ANA -ve lupus) Vasculitis.

l.c
• A/w Subacute cutaneous lupus.
ai
gm
• A/w Shrinking lung syndrome (d/t diaphragmatic
@
60

palsy).
23

Antiphospholipid antibody Seen in 1/3rd SLE patients.

ik
hv

Indicates warm Ab Autoimmune Hemolytic Anemia

rit

Anti RBC
|

(IgG).
w
ro

Anti platelet Causes 2˚ ITP in SLE.

ar
M

Anti Glutamate/ • M/c Antibodies in CNS lupus.

©

anti Neuronal • A/w cognitive dysfunction.

Anti - Ribosomal - P A/w psychosis/depression in lupus.
FACTORS CORRELATING WITH DISEASE ACTIVITY IN SLE
1. anti ds - DNA titres. 3. ↓ CRP, ↑ ESR.
2. ↓ C3, ↓ C4 levels.
Symptoms and Manifestations of SLE  00:22:42

Constitutional Symptoms (most striking) :

Fever, fatigue, weight loss.
MANIFESTATIONS
Musculoskeletal :
• Chronic inflammatory polyarthritis, • Non erosive.
multisystem involvement. • Deformity d/t laxity of ligament :
• B/L symmetrical small joints of Jaccoud’s arthropathy.
upper limb affected.
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 Rheumatology Revision - 2 69

Mucocutaneous : ----- Active space -----

Cutaneous Lupus Erythematosus (CLE) Description of Rash

Localized Rash (AKA butterfly rash):
Acute (ACLE) • Malar, photosensitive, ± scaling
1. Localised Rash (M/c) • Non scarring, highly erythematous
2. Generalised Rash - Rare • A/w oral ulcers (Hard palate)
3. Toxic epidermal necrolysis • Spares nasolabial folds
• Non premalignant
Rash : Malar rash
Subacute (SCLE) • ↑ photosensitivity, Non scarring
1. Annular SCLE (M/c) • A/w anti Ro/La : ↓ Nephritis, vasculitis risk.
2. Psoriasiform SCLE • Spares mid facial region
• A/w HLA DR3

Discoid Rash :
Chronic (CCLE) (or) Disseminated LE (DLE) : • Site : Face, scalp, neck

om
• M/c : Discoid Rash • Deep circular erythematous
SCLE

l.c
• 5/20 rule : • Dermal atrophy + follicular plugs

ai
- 5 % discoid rash SLE • Premalignant risk for SCC
gm
- 20 % SLE Discoid rash • Scarring alopecia
@
60

• Carpet track sign on back.

23
ik

CNS involvement :
hv
rit

• Cognitive dysfunction (M/c) : Anti glutamate antibody.

|
w

• Psychosis, Depression : Anti ribosomal - P Antibody.

ro
ar

• Axial skeleton spared ; No entrapment neuropathy.

M

Disseminated DLE
• Small fibre neuropathy can be seen.
©

Ocular :
2˚ Sjogren syndrome (M/c), absent uveitis.
Lung : Hematological :
• Pleuritis ± effusion : • Anemia of chronic disease, warm Ab
- Lymphocytic exudate. AIHA.
- Normal sugars. • Leucopenia.
- Risk of malignancy related effusion. • Thrombocytopenia (2o ITP).
• Diffuse alveolar haemorrhage : • ↑ Risk of DLBCL.
Marker of high disease activity.
CVS :
Cardiac Manifestations :
• Pericarditis without tamponade (M/c).
• Mitral regurgitation (M/c valvular heart disease).
• Libman sacks endocarditis (Vegetation on undersurface of valve cusps).

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 70 Medicine

----- Active space ----- Vascular Manifestations :

• ↑ risk of acute coronary syndrome (After 5-10 years).
• Small vessel vasculitis (Leucocytoclastic Angitis).
• Dangerous forms : GI and CNS vasculitis.
Renal :
Class Type & features Treatment
1 Minimal Mesangial
No treatment required
2 Mesangioproliferative
Focal
3
( < 50 % Glomeruli involved)
Diffuse ( > 50 % Glomeruli involved)
- M/c type
- Most dangerous type
Investigations :
4 Aggressive Immunotherapy

om
1. Immunofluroscence (IF) :

l.c
- Full house appearance (IgG, IgM, IgA, C1q, C3 seen)

ai
2. Electron microscopy : gm
- Hematoxilin bodies of Gross
@
60

• Rx : MMF + CNI based

23

regimes
ik

5 Lupus membranous Nephropathy ( ↓ Risk for CKD)

hv

• Refractory to steroid
rit

therapy
|
w
ro

DIAGNOSTIC CRITERIA
ar
M

SLICC : ≥ 4 criteria ( At least 1 clinical and 1 laboratory criteria) or biospy proven

©

lupus nephritis with positive ANA/Anti - DNA).

Treatment of SLE 00:36:55

Mild to moderate SLE : Skin + Joint involved only.

Only steroid + Hydroxycholoquine + Methotrexate + Belimumab ( B - Lymphocytestimulation inhibitor)
(If arthritis + )
Severe SLE (Organ involved/Life threatening) :
• IV methyl prednisolone Oral prednisolone + IV cyclophosphamide/Mycophenolate mofetil (MMF)
• Assess response to Rx X 3 months
- Good : Maintenance Rx X 3 years ( Oral steroids + MMF > Axathioprine).
- Poor : Change cyclophosphamide No response after 6 Rx : Rituximab
to MMF or vice versa months (Resistant Lupus)
Indications for plasmapheresis in SLE :
• Diffuse alveolar haemorrhage.
• CNS vasculitis.

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 Rheumatology Revision - 2 71

Classification of Spondyloarthritis  00:39:46 ----- Active space -----

Types :
Axial Predominant Peripheral predominant
1. Non - radiographic spondyloarthritis 1. Reactive arthritis
2. Radiographic spondyloarthritis 2. Psoriatic arthritis
3. IBD arthritis (Enteropathic arthritis)
4. Juvenile onset spondyloarthritis.
Features :
• Extra - articular manifestation : • Axial component : Sacroilitis.
Asymmetrical, anterior, alternating, • Age < 40 years.
anterior uveitis (M/c). • Major central pathogenic cytokine :
• HLA B27 +ve TNF α.
• RF -ve • Males > females.

om
Axial Predominant Spondyloarthritis

l.c
00:42:39

ai
gm
NON-RADIOGRAPHIC SPONDYLOARTHRITIS
@

• Symptoms: +
60
23

• MRI : Sacroiliitis
ik
hv

• HLA B - 27 +
rit

• Normal X-ray
|
w

• 5 - 10 % of patients 5 - 10 yrs Radiographic Spondyloarthritis.

ro
ar

RADIOGRAPHIC SPONDYLOARTHRITIS
M
©

• AKA Ankylosing spondylitis.

• M:F=3:1
• Age : Late teens to early twenties.

Disease Progression :
Inflammatory Erodes annulus Syndesmophyte formation
Bony Bamboo
granulation fibrosus + Calcification (Thin, marginal,
ankylosis spine.
tissue of its peripheral fibers symmetrical)
Clinical Features :
• Chronic presentation (> 3 months).
• Inflammatory alternating buttock / Deep lower back pain.
- Early morning stiffness (> 30 mins) Improves with activity.
- Nocturnal awakening due to pain.
- d/t B/L Symmetrical Sacroiliitis (ascending).
- M/c complication : Spinal fracture (C5 - C6).
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 72 Medicine

----- Active space ----- • Enthesitis : • Extra-articular Manifestations :

- Achilles tendinitis and plantar - Uveitis (most common).
fasciitis. - Lung : B/L upper lobe fibrosis.
- Costo/Manubriosternal joint : - Cardiac : Aortic regurgitation.
Chest pain. - Renal : 2° IgA nephropathy.
• Root Joint Involvement : Hip and - Osteoporosis.
shoulder joint arthritis.
Investigations :
1. X - ray : IOC.
Findings :
- Sacroiliitis.
- Bony ankylosis : Bamboo spine.
- Square wave vertebrae.
- Secondary sclerosis : Shiny corner sign. Clinical Test : Modified Schober Test

om
- Bony erosions : Romano sign.

l.c
ai
- Interspinous ligament calcification : Dagger sign.
gm
@

- Apophyseal joint capsule calcification : Trolley track sign.

60

2. MRI : STIR (T2) sequence to detect sacroilitis.

23
ik
hv

TREATMENT OF AXIAL PREDOMINANT SPONDYLOARTHRITIS

rit

• First line : NSAIDS (Indomethacin Reverses disease progression) +

|
w

Physiotherapy.
ro
ar

• TNF - α inhibitors.
M
©

• IL - 17 antagonists : Secukinumab.
Note :
Diffuse idiopathic skeletal hyperostosis (DISH) :
• Flowing candle wax appearance (d/t ligamentous calcification).
• A/w metabolic syndrome.
• Intervertebral disc space preserved : No sacrolitis.
Peripheral Predominant Spondyloarthritis 00:55:43

REACTIVE ARTHRITIS
Causes :
• Post infective ( After 2-4 weeks) :
Infection Organism M : F ratio
Genitourinary Tract Chlamydia trachomatis (M/c world wide) M >> F
Gastrointestinal Tract Shigella flexneri (M/c : India) M =F
• β -hemolytic streptococcus
Upper respiratory tract -
• Chlamydia pneumoniae

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 Rheumatology Revision - 2 73

Note : Neisseria and E. coli do not cause reactive arthritis. ----- Active space -----

• HLA B27 +ve : ↑ Risk for chronic reactive arthritis.

Features and Manifestations :
• Peripheral predominant • Enthesitis.
spondyloarthritis : • Dactylitis : Sausage digits.
- Asymmetrical (LL > UL) • Mucocutaneous features :
oligoarthritis. - Keratoderma blenorrhagica.
- Additive and painful. - Circinate balanitis.
- Acute onset + Sterile/non- • Extra - articular Manifestations :
purulent. Aortic regurgitation.
• Axial Arthritis :
- Asymmetrical sacroilitis
- Syndesmophytes : Thick,
non-marginal, coarse, fluffy,

om
l.c
asymmetrical.
ai
Treatment : gm
@

• NSAIDs : Indomethacin.
60
23

• Chronic reactive arthritis : Sulfasalazine.

ik
hv
rit
|
w
ro
ar
M
©

Keratoderma blenorrhagica Circinate balanitis Dachylitis

IBD ARTHRITIS
• Crohn’s disease > Ulcerative colitis. • 10 % cases : Ankylosing
• M = F. Spondylitis like arthritis (HLA
• 25 % cases : Peripheral predominant arthritis. B27 +ve).
Types :
Type I : LMAP Type II : SMAP - U
Large joint predominant (m/c : knee),
Small joint predominant, Migratory, Aggressive,
Migratory, Asymmetrical, Pauci articular
Polyarticular arthritis + Uveitis
arthritis
Correlates with bowel disease activity Does not correlate with bowel disease activity
Self limiting -
Treatment :
DOC : TNF α inhibitors.

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 74 Medicine

----- Active space ----- PSORIATIC ARTHRITIS

• 60/20/20 rule : • Male = Female.
- 60 % : Psoriasis f/b Arthritis. • Age: > 40 years.
- 20 % : Psoriasis and Arthritis concurrently. • HLA CW*0602 +ve.
- 20%: Arthritis f/b Psoriasis.

Clinical features :
• Peripheral predominant arthritis :
Arthritis mutilans
- Plaque psoriasis > Pustular psoriasis (Severe destructive arthritis a/w HIV).
• Enthesitis.
• Dactylitis.
• Nail changes :
- Pitting (m/c).
- Onycholysis.

om
- Horizontal ridging.

l.c
- Yellowish nail margin.
ai
gm
- Oil drop sign. Nail pitting Onycholysis
@
60

• Extra-articular manifestations :
23

- Aortic regurgitation and chronic B/L posterior uveitis.

ik
hv
rit

Patterns of Psoriatic Arthritis :

|

• Symmetric polyarthritis (M/c). • Pure DIP arthritis.

w
ro

• Asymmetric oligoarthritis. • Arthritis mutilans.

ar
M

• Axial arthropathy : Cervical spine involved,

©

thick, asymmetrical, non-marginal, coarse, fluffy syndesmophytes.

X-ray findings :
Pencil - in - cup • Ray pattern : Involvement of DIP, PIP • Arthritis mutilans.
deformity & MCP joints (Characteristic). • Whiskering : Marginal erosion
• Pencil - in - cup deformity : with adjacent bony proliferation.
Metatarsophalangeal joints. • Ivory phalanx.
Treatment :
• First line : TNF - α inhibitors.
• Second line : Methotrexate.
• Others :
- IL - 17 inhibitors : Secukinumab.
- IL - 12/23 inhibitors : Ustekinumab.
- JAK inhibitors : Tofacitinib, Baricitinib.
- PDE - 4 inhibitors : Apremilast.
Ray pattern

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 Rheumatology Revision - 2 75

COMPARING MANIFESTATIONS OF SPONDYLOARTHRITIS ----- Active space -----

Ankylosing Spondylitis Reactive Arthritis IBD Arthritis Psoriatic Arthritis

Asymmetrical Asymmetrical involvement
Laterality/Symmetry B/L sacroiliitis B/L sacroiliitis
involvement
Thin marginal Thick non - marginal Thin marginal Thick, non - marginal
Syndesmophytes
symmetrical asymmetrical symmetrical asymmetrical
Enthesitis + +++ - +++
Dactylitis - +++ - +++
Mucocutaneous
Skin and Nail changes - - Nail changes
manifestations
Uveitis a/w
Ocular Anterior uveitis Anterior uveitis B/L chronic posterior uveitis
SMAP. u

Summary of Arthritis 01:15:35

om
l.c
Chronic symmetrical small joint arthritis Acute asymmetrical oligoarthritis Monoarthritis
ai
gm
• Rheumatoid arthritis.
@

• SLE/SLE - like arthritis

60

• Reactive arthritis • Crystal arthritis (MTP joint)

• Psoriatic arthritis (DIP joint +)
23

• Psoriatic arthritis • Septic arthritis (Knee + )

ik

• Calcium pyrophosphate deposition disease

hv

(CPPD)
rit
|
w
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Non-inflammatory arthritis Inflammatory non-erosive arthritis Erosive arthritis

ar
M

• Osteoarthritis. • Rheumatoid arthritis

©

• Asymptomatic CPPD. • SLE • Chronic tophaceous gout

• Calcium oxalate crystal disease. • SLE-like arthritis • Peripheral
• Calcium hydroxy apatite deposition disease. spondyloarthritis

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 76

----- Active space ----- RHEUMATOLOGY REVISION - 3

Classification of Vasculitis  00:00:37

Vasculitis
Based on size of the predominant vessel involved Single organ vasculitis 2˚ vasculitis

a. Large vessel : b. Medium vessel : c. Small vessel d. Variable vessel :

• Giant cell arteritis • Kawasaki (M/c : Venules) • Bechet’s disease
(GCA) • Polyarteritis • Cogan’s syndrome
• Takayasu arteritis nodosa (PAN)

a. Anti Neutrophilic Cytoplasmic Antibody (ANCA) : b. Immune Complex Mediated :

om
• Granulomatosis with Polyangiitis (GPA) • IgA vasculitis (Henoch-Schonlein purpura)

l.c
• Microscopic Polyangiitis (MPA) • Cryoglobulinemic vasculitis (CAV)

ai
• Eosinophilic Granulomatosis with Polyangiitis gm
• Goodpasture Syndrome (GPS)
(EGPA). • Hypocomplementemic urticarial vasculitis
@
60

(HUV) : Anti C1q antibodies.

Secondary vasculitis :
23
ik

Causes :
hv
rit

1. Connective tissue diseases (CTD) : 2. Lymphoproliferative malignancy.

|
w

• Immune complex (IC) mediated 3. Drug Induced :

ro
ar

small vessel vasculitis (M/c). • IC mediated vasculitis.

M

• Medium vessel involvement : • ANCA vasculitis : Hydralazine, PTU,

©

- Rheumatoid arthritis : Gangrene, minocycline, levamisole.

GI vasculitis. 4. Infections :
- SLE : CNS vasculitis, GI vasculitis. • HBV : Vasculitis similar to PAN.
a. Only CTD causing aortitis : IgG4 related disease. • HCV : Vasculitis similar to Cryoglobulinemia.
Note : Cogan’s Syndrome Aortitis + Interstitial keratitis + vestibulitis (SNHL).
Temporal Arteritis and Takayasu Arteritis 00:08:52

Pathogenesis :
• Transmural inflammation of vessel wall (Granulomatous inflammation).
• a/w HLA DRB1*04.
Note : Causes of granulomatous Vasculitis.
• GPA • Rheumatoid arthritis
• EGPA • Cogan’s Syndrome
• Temporal arteritis • CNS vasculitis
Temporal arteritis
• Takayasu arteritis
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 Rheumatology Revision - 3 77

TEMPORAL ARTERITIS (GIANT CELL ARTERITIS) VS. TAKAYASU ARTERITIS ----- Active space -----

Temporal Arteritis Takayasu Arteritis

• Age : > 50 years (Median : 72 years) • Age : <40 years (Median : 25 years)
Features
• F>M • F >> M
Superficial temporal (M/c) > vertebral > • Left subclavian artery (m/c)
ophthalmic > Posterior ciliary artery (Causes • Aorta
Arteries affected
altitudinal hemianopia & is a/w Anterior • Mesenteric, coronary arteries
Ischemic optic neuropathy) • Renal, pulmonary artery ±
Typical GCA (m/c) :
• Upper limb claudication (m/c)
• New onset headache + ↑ ESR
• Asymmetry in pulse & BP
• Jaw claudication
• Carotid/Aortic bruit +
• Temporal artery tenderness
Clinical Symptoms • Renovascular hypertension especially
• Visual symptoms
in young Indian females
• a/w Polymyalgia Rheumatica (PMR)
• Renal & pulmonary involvement can be
Atypical GCA : seen

om
• Pyrexia of unknown origin (PUO)

l.c
• 10C : Temporal artery biopsy (skip lesions) • IOC : CT angiogram

ai
Investigations • Doppler ultrasound gm • Best Ix : MR Angiogram
• PET scan : Rule out aortitis • Gold standard : Arteriography
@
60

• Steroids : Immediately started in suspected

23

Steroids ± surgical revascularization

Treatment GCA (To avoid vision loss)
ik

(Especially renal artery involved)

hv

• Relapse : Tocilizumab (IL-6 inhibitor)

rit

Note : Polymyalgia Rheumatica (PMR).

|
w

• A/w GCA with ↑ ESR ( > 50).

ro
ar

• Good response to low dose steroids.

M
©

• C/F : Pain + Stiffness of hip, shoulder and pelvic girdle.

ANCA Vasculitis  00:20:18
• Antibodies against Proteinase 3 or Myeloperoxidase (MPO) in neutrophilic granules.
• ANCA study :
- Screening test by Indirect Immunofluorescence (IIF)
- Confirmatory test : ELISA (For p - ANCA).
IIF PATTERNS
Cytoplasmic Perinuclear
True + C - ANCA True + p - ANCA False + p ANCA
Ab against Proteiase-3 + - -
Ab against MPO - + -
• Renal limited vasculitis (M/c) • Type 1 autoimmune hepatitis
• GPA ( 70 - 75 %)
• MPA ( 50 %) • Primary sclerosing cholangitis
• MPA ( 40 %)
Causes • EGPA, GPA • RA, IBD
• Renal limited vasculitis
• Drugs (Hydralazine) • Infective endocarditis
• EGPA
• Goodpasture syndrome • Cystic fibrosis
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 78 Medicine

----- Active space -----

Cytoplasm pattern : C-ANCA + Perinuclear pattern : p-ANCA +

GPA V/S MPA V/S EGPA V/S PAN
GPA EGPA
MPA PAN
(Wegner’s granulomatosis) (Churg strauss syndrome)
C - ANCA > p ANCA p - ANCA > C - ANCA
ANCA - -
(Pauci immune) (Pauci - immune)
Necrotising small vessel vasculitis Eosinophils + Fibrinoid Focal necrotising
Vasculitis
( Neutrophils + Fibrinoid necrosis) necrosis inflammation

om
l.c
Granuloma + - + (Extravascular) -

ai
gm
Age > 40 yrs Elderly - -
@
60

Vessels affected Small vessels Small + Medium vessels Medium vessels

23

Constitutional +
ik

- + -
hv

Symptoms (Weight loss)

rit

• Mainly GPA • Subglottic stenosis

Asthmatic phase
|

• Sinusitis (Staph. aureus) • Serous otitis media

w

URT Symptoms • SNHL +

ro

• Midline nasal Vasculitic phase

ar

deformities
M
©

• Seen in most cases

• Thick walled cavitating
Diffuse alveolar Fleeting lung infiltrates
LRT Symptoms nodules Lung spared.
haemorrhage (Asthma like featues)
• Diffuse alveolar
haemorrhagic
• Rapidly proliferating glomerulonephritis
Rare (Mild in severity if
Kidney Symptoms (RPGN) - Type 111 Kidney spared.
present)
• Seen in all MPA cases
Minor Manifestations

Ocular Scleritis - - -
Nodules, ulcers,
Skin + + + + (Purpura) + gangrene,
Livedo reticularis
+ + + (Cranial Mononeuritis
Neuropathy ++ + neuropathy, Mononeuritis multiplex or
multiplex) polyneuropathy

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 Rheumatology Revision - 3 79

Other features : ----- Active space -----

1. EGPA :
- Eosinophilic gastroenteritis.
- Eosinophilic Myocarditis (M/c cause of death).
2. PAN :
- a/w Hepatitis B positivity & Hairy cell leukemia.
- Microaneurysms + (MR Angio > CT angiography).
- Involvement of : Diffuse alveolar haemorrhage
• Bronchial artery : Hemoptysis.
• Testicular artery : Tender/pain.
• Renal artery : RVH.
- Poorest prognosis.
TREATMENT OF ANCA VASCULITIS
First line : Steroids + oral/IV Cyclophosphamide (or) Rituximab.

om
Maintenance : Azathioprine > mycophenolate mofetil.

l.c
ai
EGPA : IL - 5 Antagonist (Mepolizumab). gm
@

Immune Complex Mediated Vasculitis 00:37:21

60
23
ik

IgA vasculitis Cryoglobulinemia

hv

• Children (< 5 years) : M > F

rit

Age Middle aged females

|

• Adults : M
 ore severe renal involvement
w
ro

Non thrombocytopenic palpable purpura • Confluent purpura

Skin
ar

in lower limb (IgA) : 100% cases • Medium vessel involved : Ulcers, gangrene
M
©

• Abdominal angina (M/c) : Severe abdominal pain.

• Intussusception (Dangerous complication)
Hepatitis C Virus (HCV) a/w Type 2, 3 of
GIT • Testicular torsion
cryoglobulinemia
• Scrotal swelling
• Blood in stool
Mnemonic : KLMNO arthritis
• Knee joint predominant
Joints • Large joint SLE like arthritis a/w myalgia
• Migratory, Non-deforming
• Oligoarthritis
• IgA nephropathy (Self limiting)
Renal Membranoproliferative glomerulonephritis (MPGN)
• RPGN
3 types :
• Type 1 : Monoclonal IgM a/w Waldenstrom’s
Types - disease
• Type 2 : Monoclonal IgM + Polyclonal IgG (RF + )
• Type 3 : Polyclonal IgG (RF + )
• Joint and GIT manifestations : Rx Steroids • HCV management
Rx
• Good prognosis in children. • If severe : Rituximab

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 80

----- Active space ----- RHEUMATOLOGY REVISION - 4

IgG4 Related Disease 00:01:05

FEATURES
• Age : >60 years; M>F.
• Subacute presentation.
• Constitutional symptoms without fever and arthritis.
PATHOPHYSIOLOGY
TGF-β
Chronic antigenic ↑↑ IgG4 Activate ↑ collagen Fibrosis >> Inflammation.
stimulation myofibroblasts formation

om
(Galectin-3)

l.c
ai
gm
Histology findings :
@

• Tumefactive lesions/lymphadenopathy.
60
23

• Storiform fibrosis (Swirling/cart-wheeling).

ik
hv

• Obliterative phlebitis.
rit

• Mild eosinophilia (H/o atopy + ).

|
w
ro

• No fibrinoid necrosis/granuloma. Storiform fibrosis

ar
M

CLINICAL MANIFESTATIONS
©

Major Manifestations :
Submandibular Lacrimal glands Retroperitoneal
Type 1 autoimmune pancreatitis
glands swelling swelling fibrosis (RPF)
• M/c manifestation.
• Young age group.
• Presentation : Obstructive • Painless/asymptomatic B/L
Present as :
jaundice > acute pancreatitis. symmetrical swelling. Submandibular gland swelling
B/L obstructive
• Exocrine + endocrine pancreatic • Minor sicca symptoms
nephropathy.
insufficiency (Type 3c DM). (Good response to steroids).
• Sausage shaped, large
pancreas + irregular borders.
Note :
Parotid + submandibular + lacrimal gland swelling
Previously Mikulicz syndrome.

Sausage-shaped pancreas
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 Rheumatology Revision - 4 81

Minor Manifestations : ----- Active space -----

Organ/system Manifestations
• Lymphocytic hypophysitis (Postpartum + headache).
CNS
• Pachymeningitis (Brain parenchyma spared).
Eye Orbital pseudotumour (Painful inflammatory mass).
• Bronchovascular bundle thickening.
Lungs • Non-specific interstitial pneumonia (NSIP) : Risk of ILD.
• Paravertebral mass.
Vascular Vasculitis : Proximal aortitis (Only vasculitis affecting aorta)
Biliary tract IgG4 sclerosing cholangitis (Previously : Primary sclerosing cholangitis).
Thyroid Reidel’s thyroiditis.
Renal Tubulointerstitial nephritis > Membranous nephropathy (Low complements).
Lymphatic Lymphadenopathy ±.
INVESTIGATIONS

om
• Serum IgG4 levels : ↑/Normal.

l.c
• Best Ix : Biopsy ↑ IgG4/IgG ratio in sample.
ai
gm
TREATMENT
@
60

• First line : Steroids (Excellent response in 2 weeks).

23
ik

• Relapse : Rituximab (Steroid sparing).

hv
rit

Sarcoidosis
|

00:19:00
w
ro
ar

FEATURES
M

• Age : >18 years.

©

• M=F.
• Histology : Non-caseating granulomas >> caseating.
• Immune paradox : ↑ T-lymphocytes in granuloma  Lymphopenia.
(↑ infection risk)
BASED ON DISEASE PROGRESSION
Spontaneous resolution (M/c).
Prognosis Mortality (5%).
Chronic disease (25%).
Acute Sarcoidosis :
Lofgren syndrome Heerfordt-waldenstrom syndrome
1. Arthritis. 1. Uveitis.
Triad 2. Hilar lymphadenopathy. ± fever, ± uveitis. 2. Parotitis. ± fever
3. Erythema nodosum. 3. 7th nerve palsy.

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 82 Medicine

----- Active space ----- Lofgren syndrome Heerfordt-waldenstrom syndrome

• Arthritis (Misnomer) : Acute onset painful
B/L ankle joint tenosynovitis.

• Garland sign
Lymphadenopathy :
1. Paratracheal.
2. Right hilar. M/c manifestations :
3. Left hilar. • Neurological : B/L LMN 7th
Features nerve palsy.
• Ocular : Acute B/L symmetrical
• Erythema nodosum : anterior uveitis.
Mnemonic 3P’s.
Painful.
Pre-tibial.
Papule without
pigmentation.

om
l.c
• Prognosis : Good (HLADRB1*03)

ai
gm
Note : Condition Uveitis
@
60

Spondyloarthritis Acute anterior alternating asymmetrical uveitis

23
ik

Behcet’s disease Posterior uveitis

hv
rit

Chronic Sarcoidosis :
|
w

Lung > skin > eye.

ro
ar

Eyes : Chronic uveitis, panuveitis, retinal vasculitis.

M
©

Skin : Lupus pernio (Maculopapular/nodular).

Lung : Lupus pernio
• Interstitial lung disease : M/c cause of death.
• Upper lobe ILD : NSIP.
• Bronchovascular bundle thickening.
• No paravertebral mass/aortitis.
• Small airway disease and endobronchial obstruction + .
• Stages : Scadding scoring system (Based on CXR). Stage 1
Stage 1 : B/L hilar lymphadenopathy.

Stage 2 : • ↓ hilar lymphadenopathy.

• ↑ lung infiltrates.
Stage 3 : ↑↑ Lung infiltrates.

Stage 4 : Fibrosis. Infiltrates with fibrosis Stage 2

• Clinical paradox (Lymph node size ↓, disease ↑).
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 Rheumatology Revision - 4 83

Head to toe manifestation : ----- Active space -----

Organ system Manifestations

• B/L LMN 7 nerve palsy (M/c) : A/w Heerfordt syndrome.
th

• Acute transverse myelitis.

CNS
• Central Diabetes Insipidus.
• Leptomeningeal enhancement.
Eye May affect any compartment.
Salivary glands Parotitis (Heerfordt’s) > parotid swelling.
Cardiac Dilated cardiomyopathy, conduction blocks.
Vascular Immune complex mediated small vessel vasculitis.
Joint Arthritis, bone cyst, bone erosions.
Liver Intrahepatic cholestasis.
AKI (Prerenal) : Hypercalcemia.
Kidney (↑ 1 α hydroxylase from granuloma ↑ vit D3).

om
CKD : Tubulointerstitial disease.

l.c
Bone marrow (Rare) Pancytopenia, splenomegaly.

ai
gm
Note :
@
60

Connective tissue disease causing erosive arthritis : MCTD > sarcoidosis.

23
ik

MANAGEMENT
hv
rit

Investigations :
|
w

• Endobronchial ultrasound (EBUS) + transbronchial biopsy IOC.

ro
ar

• PET scan (Localization).

M

Treatment :
©

• 1st line : Steroids.

• 2nd line : Methotrexate, azathioprine, hydroxychloroquine.
• 3rd line : TNF-α inhibitors.

Sjogren’s Syndrome 00:38:37

FEATURES
• Multisystem autoimmune CTD (2nd m/c).
• Middle aged ; F >> M.
• Dry eye + dry mouth (Autoimmune exocrinopathy).
• 50% case : Extraglandular manifestations Serious (Some cases).
• 2° Sjogren’s : M/c cause Rheumatoid arthritis > SLE.

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 84 Medicine

----- Active space ----- CLINICAL MANIFESTATIONS

Glandular :
Salivary gland swelling :
• IL-18 mediated swelling.
• M/c : Parotid gland.
• Sicca symptoms +++ (Steroid non-responsive).
• Asymmetric painful enlargement ↑ risk of marginal zone B-cell lymphoma.
• Raynaud’s phenomenon Precede sicca symptoms (Some cases).
Extraglandular :
Organ system Manifestation
Joint Arthralgia/arthritis (Jaccoud’s) : M/c extraglandular manifestation
CNS Ganglionopathy (Classical)
Ocular Dry eye

om
Endocrine Thyroid disorders

l.c
NSIP : Lymphoid Interstitial pneumonia (LIP)
ai
Lung gm
(Ground glass opacities + nodules + cysts)
@

Vascular Immune complex mediated small vessel vasculitis

60
23

Cardiac Pericarditis
ik
hv

• Primary Biliary cirrhosis (PBC)

Liver
rit

• A/w Hepatitis C virus (HCV)

|
w

Kidney Distal Renal Tubular Acidosis (RTA)

ro

Note :
ar
M

Other conditions associated with HCV :

©

• Cryoglobulinemia type 2, 3.
• Porphyria cutanea tarda.
• Cutaneous lichen planus.
• Membranoproliferative glomerulonephritis (MPGN).
INVESTIGATIONS :
• Antibodies :
a. Anti Ro :
- A/w early onset, long duration disease.
- ↑ risk Extraglandular manifestations.
Lymphoma.
- Bad prognosis.
b. Anti La.
• Biopsy : Gold standard for diagnosis.

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 Rheumatology Revision - 4 85

Systemic Sclerosis 00:49:03 ----- Active space -----

Risk Factors :
1. Environmental agents and drugs :
• Silicosis. • Vinyl chloride.
• Bleomycin. • Contaminated L-tryptophan.
• Pentazocine.
2. Genetic factors.
Pathogenesis :
Risk Vasculopathy Thrombosis Capillary hypoxia TGF-β Fibrosis.
factors (Small vessel (Myofibroblast Collagen (No inflammation;
endothelial injury) activation) formation ESR, CRP : N/↓)
Types of Systemic Sclerosis (SSc) :
1. Diffuse SSc : Skin lesions anywhere in the body.

om
2. Limited SSc : Limited to face and distal to elbow.

l.c
ai
3. Sine scleroderma : No skin lesions. gm
@

Features & Manifestations :

60

• Raynaud’s phenomenon (RP) :

23
ik

- Episodic vasoconstriction (D/t cold > stress/vibration).

hv
rit

- A/w PCR : Pallor Cyanosis Redness.

|
w

- 2° RP (Most dangerous) :
ro

Raynaud’s phenomenon
ar

a. Critical limb ischemia Gangrene.

M

b. Nail fold capillaroscopy Dilatation and dropout of capillaries.

©

Features of Limited SSc vs Diffuse SSc :

Limited SSc Diffuse SSc
Pathogenesis Vasculopathy. Fibrosis.
Severe, long standing
2° RP Short-lasting, ↓ severe, ↓ painful.
(Critical limb ischemia + ).
• Dry skin + tightening.
• Hyperpigmentation.
• ↓ tightening.
Skin changes • Alopecia.
• ↑↑ telangiectasia.
• Loss of body oil.
• Salt and pepper skin.
Cardiac
Renal
Lung (ILD)
↓/ - +
Tendon friction rub
Joint contractures > arthralgia,
Bone/joint Acral osteolysis Erosive arthritis.
myalgia.

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 86 Medicine

----- Active space ----- Limited SSc Diffuse SSc

CREST syndrome :
• Calcinosis cutis : Calcium
hydroxyapatite deposition Mask facies :
Characteristic (Subcutaneous). • Microstomia.
feature • Raynaud’s phenomenon. • Pursed lips.
• Esophagitis (M/c GI feature). • Puckered mouth.
• Sclerodactyly.
• Telangiectasia.
Gastric Antral Vascular Ectasia (GAVE).
GI features • LES tone loss : Recurrent oesophagitis.
(D/t ↓ motility) • Pneumatosis intestinalis. -
• Small intestinal bacterial overgrowth.
m/c cause of Pulmonary arterial hypertension (PAH)
ILD.
death (A/w ↑ telangiectasia).

om
l.c
ai
gm
@
60
23
ik
hv
rit

Critical limb ischemia Mask facies Salt and pepper skin

|
w

SSc Specific Antibodies :

ro
ar
M

Autoantibodies Associated conditions

©

Anti-topoisomerase-1 (Scl-70). Diffuse SSc.

Anti-centromere. CREST syndrome (Limited SSc).
• Diffuse SSc.
• Scleroderma renal crisis (Most specific).
• Rapidly progressing skin lesions.
Anti-RNA polymerase 3 (Anti-RNAP-3).
• GAVE (Watermelon stomach).
• Malignancy.
• Tendon friction rub.
PM/Scl-70 (Shows nucleolar pattern). Overlap syndrome (Polymyositis & scleroderma).
Investigations :
HRCT chest : Ground glass appearance NSIP.

CXR : Reticulo-nodular infiltrates NSIP pattern

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 Rheumatology Revision - 4 87

Note : ----- Active space -----

• Calcinosis cutis also seen in juvenile dermatomyositis.
• Other conditions a/w 20 RP : MCTD, Sjogren’s syndrome, anti-synthetase
syndrome.
Scleroderma Renal Crisis :
• Seen in diffuse SSc.
• Antibodies : Anti RNAP-3 > Anti-topoisomerase-I.
• Thrombotic microangiopathy (TMA).
• within 1st 4 years of disease.
• Presentation : 2° hypertension (HTN emergency) + microangiopathic hemolytic
anemia + thrombocytopenia.
• Early use of steroids in diffuse SSc Development of renal crisis.
• Rx : ACE inhibitors (↓ mortality).

om
Inflammatory Muscle Disease 01:13:31

l.c
ai
gm
Conditions :
@

a. Polymyositis (PM). e. Immune mediated necrotising

60
23

b. Dermatomyositis (DM). myopathy.

ik
hv

c. Juvenile dermatomyositis. f. Cancer induced myositis.

rit

d. Inclusion body myositis (IBM). g. Amyopathic dermatomyositis.

|
w

Polymyositis v/s Dermatomyositis :

ro
ar
M

Polymyositis Dermatomyositis
©

Age Adults Adults + children

Gender F>M
Presentation Overlap syndrome Isolated/overlap
LMN weakness (M/c) :
• B/L Symmetrical, subacute.
Muscle • LL >> UL.
Features • Proximal weakness.
• N : Sensation, reflexes, bowel & bladder function.
Skin - +
Necrosis Not seen
Cells seen CD8 T cells CD4 T cells + B cells
Muscle Endomysial + perimysial
inflammation
+
biopsy
Perivascular inflammation - +
Perifascicular atrophy - +
CPK Positive
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 88 Medicine

----- Active space ----- Skin manifestations in dermatomyositis :

• Gottron’s papule :
- Scaly erythematous, flat topped (Pathognomonic).
- Pruritis, knuckle involvement + .

Shawl sign (Photosensitive) Heliotrope rash Calcinosis cutis Holster sign

om
l.c
ai
gm
@
60
23
ik
hv
rit
|

V sign (Photosensitive) Gottron’s sign/Linear erythema Periungual telangiectasia Gottron’s papules

w
ro

Anti-synthetase Syndrome :
ar
M

• Seen in polymyositis and dermatomyositis.

©

• Antibodies Anti Jo-1.

• Presents as fever.
Findings :
1. Arthritis : SLE-like.
2. ILD : NSIP (M/c). Mechanic’s hand
3. Mechanic’s hand : Crusting & erosion of radial aspect of index
+ middle fingers.
4. Raynaud’s phenomenon.
Cancer Associated Myositis :
• Dermatomyositis >> Polymyositis > IBM.
• Antibodies : Anti TIF1 gamma, anti NXP 2.

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 Hematology Revision - 1 89

HEMATOLOGY REVISION - 1 ----- Active space -----

Hematopoiesis 00:01:30

Normal bone marrow Normal peripheral smear

(Cellularity : 100 - age)

om
l.c
Pluripotent hematopoietic stem cell
ai
gm
@

Common Myeloid Progenitor (CMP) Common Lymphoid Progenitor (CLP)

60
23
ik

RBC, platelet, granulocyte, B & T lymphocytes, NK cells.

hv
rit

monocyte (Macrophage).
|
w

RBC development :
ro
ar

CMP
M

Erythropoietin synthesis :
©

Blood forming unit (Erythroid) Peritubular interstitial fibroblast

Erythropoietin first involved in cortex & outer medulla of
(Iron independent) kidney.
Colony forming unit (Erythroid)
First iron dependent step
Proerythroblast
Early (Basophilic).

Erythroblast/ Intermediate (Polychromatic) : Hemoglobin first appears.

Normoblast
Late (Orthochromatic) Reticulocyte RBC.
Note : Supra-vital stain for reticulocyte New methylene blue/Brilliant cresyl
blue (For RNA).

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 90 Medicine

----- Active space ----- Evaluation of Anemia 00:06:57

Hemoglobin reference range for evaluation :

• Male : <13 g/dL; ≥16.5 g/dL. • Pregnancy : <11 g/dL.
• Female : <12 g/dL; ≥16 g/dL. • Chronic kidney disease (CKD) : <10 g/dL.
Laboratory Evaluation :
Retic count : Differentiates underlying cause of ↓ RBC (In %).
Decreases if ↓ production of RBC.
Increases if ↑ destruction of RBC.
Corrected retic count (To account for low hemoglobin-induced RBC production).
15 g/dL in males.
= Retic count x Hb of patient ; Where desired Hb
Desired Hb 13 g/dL in females.

om
Reticulocyte Production Index (RPI) : Best parameter.

l.c
ai
• Value = Corrected retic count (Accounts for longer reticulocyte
gm
half-life in circulation)
@

2
60
23

• Interpretation <2.5 : Hypoproliferative.

ik
hv

>2.5 : Hyperproliferative.
rit
|

Mean Corpuscular Volume (MCV) : Average volume of RBC.

w
ro

• Normal range : 80 to 100 fL.

ar
M

• If MCV >100 : Macrocytosis (Megaloblastic/Non-megaloblastic).

©

Hypoproliferative Anemia Classification 00:14:00

Symptom duration : 2 to 3 months.

RPI <2.5

MCV : Low to normal MCV : High

Iron Deficiency Anemia of Sideroblastic Thalassemia Macrocytosis

Anemia (IDA) chronic disease anemia trait

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 Hematology Revision - 1 91

Differentials : ----- Active space -----

Anemia of chronic Thalassemia Sideroblastic

IDA
disease trait (α or β) anemia
↓ (Congenital)/
MCV ↓/ N ↓/ N ↓
↑ (Acquired)
S. Iron ↓ ↓ N ↑
Total Iron Binding
↑ N /↓ N N /↓
Capacity (TIBC)
Transferrin saturation ↓ ↓ N ↑
S. Ferritin ↓ N /↑ N N /↑
S. Transferrin ↑ N N N /↑
S. Hepcidin ↓ ↑ N ↓
BM iron stores ↓ N /↑ N N /↑
Erythroblasts iron ↓ ↓ N Ring forms

om
Normocytic normochromic/ Normocytic normochromic

l.c
Peripheral smear Microcytes Dimorphic

ai
Microcytic hypochromic (Microcytes in miliary TB, RA)
gm
@
60

Iron Deficiency Anemia 00:18:18

23
ik
hv

Iron Metabolism :
rit

Iron absorption : In duodenum.

|
w

• Dietary iron 2/3rd heme iron : Absorbed via heme transporter.

ro

Heme transport
ar
M

1/3 non-heme iron (Fe

rd
Fe )
3+ 2+
©

(Absorbed via divalent metal transporter 1).

Iron storage :
• Storage forms Ferritin (M/c). DMT 1
Hemosiderin (Detected by Prussian blue).
• Sites : Marrow, macrophages, liver, duodenal enterocyte.
Iron transport : Iron uptake :

Transferrin released into circulation.

Ferroportin 1 Soluble transferrin receptor
Fe3+ taken up for erythropoiesis.

Hephaestin

Note : Ceruloplasmin converts Fe2+ to Fe3+ in brain.

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 92 Medicine

----- Active space ----- Investigations :

Iron indices :
Parameter Details Normal values
• Measure of iron stores : Earliest marker.
S. Ferritin 30-300 ng/mL
• Positive acute phase reactant (↑ value = IDA).
S. Iron Transferrin bound iron in circulation. 50-150 mcg/dL
Total Iron Binding
Measure of iron binding capacity of transferrin. 300-360 mcg/dL
Capacity (TIBC)
Transferrin (S. Iron/TIBC) x 100.
~33% or 1/3rd of TIBC
Saturation (TSAT) ↓ in IDA.
Free erythrocyte
↑ D/t lack of iron binding. -
protoporphyrin
Red cell distribution Indicates degree of anisopoikilocytosis
11.5%-14.5%
width (RDW) (Directly proportional).
Peripheral smear :

om
Negative iron balance Iron deficiency erythropoiesis Iron deficiency anemia

l.c
ai
gm Microcytic hypochromic
Normocytic normochromic
@
60

Note :
23
ik

Most specific & sensitive marker.

hv

(Soluble transferrin receptor assay (STFR)/log ferritin) >

rit
|

STFR ↑ > S Ferritin.

w
ro
ar
M

Clinical Features : Etiology :

©

General symptoms : Fatigue, • M/c etiology :

pallor, palpitations. - General : blood loss.
Specific symptoms : - Female : Menstrual loss.
1. Pica symptoms : Pagophagia - Male : GI bleed (Evaluate by
(Craving for ice). colonoscopy + upper GI endoscopy).
2. Restless leg syndrome. • Other etiology :
3. Epithelial changes : - Malabsorption : Rule out celiac disease
• Koilonychia : Nail changes. (Anti-TTG Ab, anti-endomysial Ab).
• Plummer-Vinson syndrome - CKD patient with EPO resistance.
: Dysphagia, esophageal - Nutritional deficiency.
webs.
4. Growth retardation. In growing
5. Neuro-psychiatric issues. children.
6. Alopecia.
Note : EPO should be started only after iron stores are replenished.
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 Hematology Revision - 1 93

Treatment : ----- Active space -----

• Absorbed Fe = 10% of Fe intake.
• Fe requirement = [2.2 x body weight x (Desired Hb - Patient Hb)] +1000.
• RDA Adult male : 1 mg.
Adult female : 2 mg.
Pregnancy : 3 mg.
Ferric carboxymaltose
• IV iron 1 g/500 mg injections (≥2 doses required).
Iron isomaltose
• Disadvantage of oral iron : Dyspepsia, unpleasant taste.
Response to IV treatment :
• Retic count : ↑ by 5 to 7 days Peaks in 2 weeks.
• Hb begins to rise in 2 weeks ↑ by 2 g/dL in 1 month.

om
Anemia of Chronic Disease 00:48:00

l.c
ai
AKA functional IDA. gm
@

Pathogenesis :
60
23

• IL-6 (Inflammation).
ik
hv

• Activin. +
rit
|

Hepcidin -
w

Ferroportin ↓ mobilisation of
ro

• Erythroferrone.
ar

- Fe from stores.
M

• Hypoxia.
©

Note : Hepcidin regulation HFE gene on Chr 6.

Sideroblastic Anemia 00:53:30

Disorder of protoporphyrin synthesis.

Heme synthesis :
ALA synthase ↓ Protoporphyrin
Succinyl CoA + glycine ALA ↓ Heme.
PLP
Causes :
• Congenital : X-linked ALA synthase defect (M/c).
• Acquired :
1. Myelodysplastic syndrome (M/c). 3. Copper deficiency.
2. Lead poisoning. 4. Chloramphenicol/Pyrazinamide.
Note : Rarely alcohol Sideroblastic anemia.

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 94 Medicine

----- Active space ----- Investigations :

1. Peripheral smear :
• Dimorphic blood picture.
• Ringed sideroblasts (↑ Fe deposited as a ring).
2. Electron microscopy : Pappenheimer bodies.

Prussian blue staining

Thalassemia Trait 00:58:59

Types βOβO : Thalassemia major.

β+β+ : Intermediate.
ββO or ββ+ : Thalassemia trait/minor (Asymptomatic).

om
• Usually asymptomatic.

l.c
ai
Investigations : gm
• Confirmatory test : Serum electrophoresis.
@
60

- HbA2 : 4-8.5% (Normal : 1.5-3%).

23
ik

• Mentzer index (MCV/RBC count) :

hv
rit

- <13 for Thalassemia trait (>13 for IDA).

|

• RDW : Normal.
w
ro
ar
M
©

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 Hematology Revision - 2 95

HEMATOLOGY REVISION - 2 ----- Active space -----

MACROCYTIC ANEMIA
Hypoproliferative anemia with RPI < 2.5 & MCV > 100fL.
Types

Megaloblastic (Lag in nuclear maturation) : Normoblastic :

• B12 deficiency. • Liver disease (M/C) : Target cells.
• Folate deficiency. • Aplastic anemia.
• DNA synthesis inhibitor drugs : • COPD.
Cytarabine, 5 - FU, 6 - MP. • Scurvy.
• Thiamine deficiency. • Hypothyroidism.

om
• Orotic aciduria. • Post hemolysis.

l.c
• Alcohol.
ai
gm
Vitamin B12 and Folate Deficiency 00:05:26
@
60

Vitamin B12 :
23
ik

Metabolism :
hv
rit

• Body store : 2 to 5mg (Deficiency is rare).

|
w

• RDA : 3 to 7 μg/day.
ro
ar

• Source : Dietary animal meats.

M

• Form : Adenosylcobalamine & methylcobalamine.

©

Absorption :
Site : Process :
Adenosylcobalamine (Or) Methylcobalamine.
Stomach Combines with R factor (Haptocorrin).

D2 R factor & B12 complex is broken down.

D2/D3 B12 + Intrinsic Factor (IF) complex formation.

Ileum Complex binds to cubam receptor.

Blood B12 + Transcolabamin II.
B12 absorbed into blood.
Tissues Reaches tissues for various functions.

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 96 Medicine

----- Active space ----- Etiology of B12 deficiency :

• Pernicious anemia (Autoimmune disorder) : Ab against parietal cells of
stomach/IF.
• Ileal pathologies : Crohn’s disease, TB, tropical sprue.
• Small intestinal bacterial overgrowth (SIBO).
• Imerslund Grasbeck Syndrome :
Congenital deficiency of cubam receptor ↓ B12 + Proteinuria.
• Dietary deficiency.

Folic Acid :
Folate metabolism :
• Polyglutamate In intestinal lumen Monoglutamate (5 methyl THFA/Folate).
PPI - Homocysteine
B12
Methionine

om
THFA (For 1C transfer & DNA synthesis).

l.c
B
• Folate independent reaction : Methylmalonyl CoA 12 Succinyl CoA.
ai
gm
Etiology of folate deficiency :
@
60

1. Nutritional deficiency.
23

2. ↑ requirement in pregnancy, myeloproliferative neoplasms, hemolysis.

ik
hv

3. Drugs :
rit
|

- Methotrexate. - PPI.
w
ro

- Triamterene. - Phenytoin.
ar
M

- Pyrimethamine. - Anticonvulsants.
©

Evaluation of Vit B12 vs Folate Deficiency :

B12 Deficiency Folate Deficiency B12 + Folate Deficiency
Methylmalonic acid ↑ � ↑
Homocysteine ↑ ↑ ↑
↑
Folate (Folate trap : ↑ 5-methyl THFA d/t ↓ ↓
↓ conversion to THFA)
Evaluation of B12 deficiency :
• Check red cell folate in B12 deficiency.
• If B12 levels <200 pg/ml : B12 deficiency.
200 - 300 pg/ml : Look for methylmalonic acid & homocysteine
If ↑B12 deficiency.
>300 pg/ml : No B12 deficiency.

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 Hematology Revision - 2 97

Peripheral smear findings : ----- Active space -----

1. Megaloblasts 2. Hypersegmented 3. Howell - Jolly 4. Cabot ring 5. Basophilic stippling

neutrophils (Earliest sign) bodies

6. Pancytopenia (In 20% cases)

Pernicious Anemia :
• Autoimmune disorder d/t Ab against Parietal cell (Sensitive)  Hypergastrinemia/
↑ risk of Gastrin secreting tumor.
Intrinsic factor (Specific)
• Associated with other autoimmune disorders : Type 1 DM, vitiligo, Addison’s
disease etc.

om
• Risk factors : Females > males, age > 60y.

l.c
ai
Symptoms : gm
1. Neurological symptoms :
@
60

Progression of areas affected :

23
ik

Nerve (Neuropathy) Dorsolateral part of spinal cord Cerebrum.

hv

1. Dorsal column f/b,

rit
|

2. Lat. Spinothalamic tract f/b,

w
ro

3. Corticospinal tract.
ar
M

2. G.I symptoms : Gastritis, gastrin secreting carcinoid (Antral sparing),

©

angular cheilitis & atrophic glossitis.

Note : Tumors associated with pernicious anemia m/c in males.
Treatment :
1000 μg IM of hydroxycobalamine :
Once weekly for 6 weeks f/b Once every 3 months.
Hyperproliferative Anemia Classification 00:23:56

Hemolytic anemias : Hyperproliferation d/t hemolysis Reticulocytosis/Macrocytosis.

Causes : Inherited causes :
(All intracorpuscular, except HUS)

Hemoglobinopathies : Enzyme deficiency : Membrane defects :

• Sickle cell • G - 6 - PD • Hereditary spherocytosis
anemia • Pyruvate kinase • Elliptocytosis
• Thalassemia • 5’ nucleotidase • ovalocytosis
HUS : Hemolytic uremic syndrome.
PNH : Paroxysmal nocturnal hemoglobinuria.
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 98 Medicine

----- Active space -----

Acquired causes
(All extracorpuscular, except PNH)

Immune : Non - immune :

• Autoimmune • Drug/toxins
• Alloimmune • Infections
- Hemolytic disease of newborn (HDN) • PNH
- Febrile hemolytic transfusion reactions • Fragmentation hemolysis
• Drugs
Hemolysis Classification Based on Site :
Intravascular Hemolysis Extravascular Hemolysis
Site Within blood vessel M/C in spleen
• Dark urine : • Moderate splenomegaly
- Hemoglobinuria • Fe stores ↑
- Hemosiderinuria • Jaundice + + +
Features

om
• LDH ↑ ↑ ↑ (d/t protoporphyrin breakdown)

l.c
• Haptoglobin ↓ ↓ ↓ • Urobilinogen ↑ ↑ & stercobilinogen ↑

ai
• Jaundice + gm • LDH ↑ & haptoglobin ↓
• PNH (M/c)
@
60

• Infections : Malaria, sepsis

23

• Paroxysmal cold • Autoimmune hemolytic anemia (AIHA) : Warm

ik
hv

hemoglobinuria (PCH) • Hereditary spherocytosis

Causes
rit

• Acute G6PD deficiency • Sickle cell anemia

|

• Microangiopathic hemolytic • Thalassemia

w
ro

anemia (MAHA)
ar

• Transfusion related hemolysis

M
©

Immune Hemolysis 00:35:50

Drug induced immune hemolytic anemia :

1. Membrane modifying drug : Cephalosporin.
2. Autoantibody forming drug : Quinidine, Rifampicin, Isoniazid.
3. Anti - RBC antibody forming drug : Methyldopa.

Autoimmune Hemolytic Anemia (AIHA) :

Site of RBC destruction :
• RBC coated with warm antibodies : Spleen.
• RBC coated with complement only :
Peripheral circulation Acrocyanosis, Raynaud’s phenomenon.

Clinical presentation of warm AIHA :

• Progressive fatigue, palpitations. • Progressive ↓ in Hb.
• Moderate splenomegaly. • N TLC & platelet count.

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 Hematology Revision - 2 99

Differences of types of AIHA : ----- Active space -----

Warm AIHA Cold agglutinin disease PCH

IgG (Receptor : Polyclonal IgG
Antibody IgM
Splenic macrophage) (Donath-Landsteiner)
Site of hemolysis Extravascular Intravascular > Extravascular Intravascular
• IMN
• SLE
• Mycoplasma
• PAN
• IgM secreting tumors
Secondary causes • Lymphoma (CLL) Syphilis (Rule out)
(Waldenstrom
• RA
macroglobulinemia)
• HIV
• Lenalidomide
Steroids + Rituximab
Treatment Rituximab Supportive care
Splenectomy : Second line
Course of disease Sub-acute/Acute Chronic Acute

om
Polychromasia, spherocytes, RBC aggregation in cooler

l.c
fragmented RBC peripheral circulation

ai
gm
@

Peripheral smear Combined

60
23
ik
hv
rit
|
w

Temperature of max
ro

37°C 0 to 4°C 4°C

ar

activation of Ab
M

Mechanism of hemolysis Opsonization Complement Complement

©

Antigen Panagglutinin I antigen P antigen

Investigations :
Donath Landsteiner - - +
Direct antigen test + (IgG + , C3 +/-) + (IgG - , C3 +) +
Note :
• AIHA + thrombocytopenia : Evan’s syndrome.
• Direct Coombs test.

Diagnostic Algorithm :
Direct antiglobulin IgG + , C3 ± Warm AIHA.
Test IgG - , C3 + Peripheral smear Agglutinins Cold agglutinin disease.
No agglutinins Donath-Landsteiner test If + : PCH.

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 100 Medicine

----- Active space ----- Paroxysmal Nocturnal Hemoglobinuria 00:50:30

M/C acquired cause of intravascular hemolysis.

Pathogenesis :
X CD55 (Decay
X PIGA gene (X chromosome) Codes for GPI anchor Anchors accelerating factor). Complement
Acquired PIGA mutation proteins regulator
X CD59 (Membrane
inhibitor of reactive lysis). proteins
• PIGA gene mutation RBCs sensitive to lysis (AKA PNH III RBC).
IOC : Flow cytometry (% of PNH III RBC determines disease type).

Clinical presentation :
• High colored urine : D/t intravascular hemolysis.
• Thrombosis :
D/t defective urokinase plasminogen activator receptor (uPAR) on RBC.

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- Budd-Chiari Syndrome, Cerebral venous thrombosis.
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• Pancytopenia : Hypercellular marrow. gm
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• Refractory anemia.
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• Aplastic anemia (In 25% cases).

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Treatment : Eculizumab.
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Note : ↓ Neutrophil Alkaline phosphatase CML & PNH only.

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Fragmentation Hemolysis
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00:54:30
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Types Microangiopathic : Hemolytic uremic syndrome (HUS)/TTP.

Macroangiopathic : Cardiac hemolysis (Prosthetic valves).
HUS
Classical Features :
• Microangiopathic hemolytic anemia • Thrombocytopenia.
(MAHA). • Renal failure.
.Pathogenesis :
D/t traumatic microangiopathy.
Passage of RBC
Endothelial injury vWF released Thrombus formation Schistocyte
+ Platelet trapping formation.

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Types : ----- Active space -----

1. Childhood HUS (D+) :
• Causative organism Shigella dysenteriae type I (Shiga toxin).
EHEC O157 : H7 (Shiga - like toxin/Verocytotoxin).
• Clinical presentation :
- Dysentery.
- Rapidly progressive renal failure (RPRF) : Over few days to weeks.
• Treatment : Supportive care (Excellent prognosis).
2. Adult HUS (D-) :
• Associated with alternate complement pathway activation ↓ C3.
• Types : N C4.

Familial Type : Acquired Type :

D/t defect in alternate complement pathway - Drugs :

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• Mitomycin.

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- Complement Factor H mutation (M/C)
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- Complement Factor B mutation : Poor prognosis gm • Ticlopidine, clopidogrel (Also cause TTP).
• Cisplatin.
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- Membrane co - factor P mutation : Good prognosis

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• Calcineurin inhibitors.
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- Post Hematopoietic stem cell transplant.

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- HIV.
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• Clinical presentation : Renal failure with hypertensive crisis (Secondary HTN).

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• Treatment (Poor prognosis) :

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- Plasmapheresis (If early presentation).

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- Rituximab + Eculizumab : For recurrence post renal transplant.

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)
Classical features :
1. MAHA. 4. GI features.
2. Thrombocytopenia. 5. Fever.
3. CNS features (Stroke, headache).

Pathogenesis :
Antibody against vWF metalloproteinase (ADAMTS 13) Excess vWF Platelet trap.

Causes :
1. SLE.
2. HIV.
3. Drugs : Ticlopidine, clopidogrel.
Treatment : Plasmapheresis (PLEX) + Rituximab.
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----- Active space ----- HEMATOLOGY REVISION - 3

Myeloproliferative Neoplasms (MPN) 00:00:06

Terminal myeloid cell expansion.

Common Features :
1. No dysplasia : Mature cell expansion.
2. Extramedullary hematopoiesis Hepato/splenomegaly.
3. Can transform into one another/into Acute Myeloid Leukemia (AML).
4. Hyperviscosity Thrombosis.
5. Fatigue +/- systemic features.

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Classification :
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BCR-ABL mutation JAK-2 mutation
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Translocation of (9;22) Chr Deletion of Chr. 9p

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• Chronic Myeloid Leukemia (CML) • Polycythemia rubra vera (M/C) : 100%

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• Chronic Neutrophilic Leukemia (CNL) • Primary Myelofibrosis (PMF) : 50-60%

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• Chronic Eosinophilic Leukemia (CEL) • Essential Thrombocytosis (ET) : 50-60%

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Approach to Polycythemia :
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Male : Hb >16.5g/dL; PCV >49%

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Female : Hb >16g/dL; PCV >48%

Absolute polycythemia/erythrocytosis Relative erythrocytosis

(↑ RBC mass) (D/t ↓ plasma volume)
• Post dengue
Secondary polycythemia Primary polycythemia • Dehydration
Erythropoietin (EPO) ↑ EPO N /↓ ( N range : 4 to 10)
Management : Hydration
Hypoxia : No hypoxia : PCRV
• COPD (↑WBC, RBC & platelets)
• Smoker Paraneoplastic polycythemia
• Obstructive • Renal cell carcinoma (RCC)
sleep apnea • Hepatoma
• CO poisoning • Cerebellar hemangioblastoma
• Uterine leiomyoma
• Pheochromocytoma.

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Polycythemia Rubra Vera (PCRV) 00:04:15 ----- Active space -----

Clinical Presentation :
• Population at risk : >50y; female preponderance.
Symptoms :
Specificity Presentation
↑ RBC Non specific to PCRV Systemic HTN, vertigo, headache, thrombosis.
Basophilia Aquagenic pruritis, hyperuricemia,
↑ WBC ↑ Transcobalamin-1 ↑Vit B12 binding capacity,
Specific to PCRV ↑risk of AML.
Acquired Von Willebrand Disease (VWD), microvascular Erythromyalgia
↑ Platelet thrombosis Erythromyalgia (Burning pain in hand & feet).

Laboratory investigations :

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1. ↑ Hb.

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2. ↑ WBC.
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3. ↑ platelets.
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4. Microcytic erythrocytosis (MCH compensated by ↓ MCV).

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5. ESR ↓↓.
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Note : Microcytic erythrocytosis only in thalassemia, PCRV & hypoxia.

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WHO diagnostic criteria : (2 major + 1 minor/3 major for diagnosis)

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Major criteria Minor criteria

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1. Hb Male >16.5g/dL
Female >16g/dL
2. JAK-2 mutation + V617F mutation (M/c) N /↓EPO.
Exon 12 mutation
3. Bone marrow biopsy Hypercellularity with panmyelosis

Treatment :
1. <60 yrs Aspirin + phlebotomy (Target Hb : 12 to 13g/dL).
2. >60 yrs or h/o stroke Add ruxolitinib (JAK 1/2 inhibitor).

Primary Myelofibrosis (PMF) 00:12:57

Associated mutations :
• JAK2 mutations (M/C) : 50-60%
• Calreticulin mutation Triple negative : Very poor prognosis.
• MPL mutation (Thrombopoietin)

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----- Active space ----- Clinical presentation :

• Population at risk : 60 to 70 y; Male = Female.
• Prognosis : Poor.
• ↑ risk of thrombosis & AML (Risk lower than in PCRV).
• Disease progression :
Hypercellular marrow (Initial phase)

Megakaryocyte dysplasia (Cloud megakaryocyte)

Produces
TGF-β

Bone marrow fibrosis

Bone marrow fibrosis :
1. Pancytopenia Fatigue (M/C symptom).
2. Leucoerythroblastic blood picture :

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• Left shift.

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• Dacrocytes (Teardrop RBCs) + .
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3. Hepatomegaly & massive splenomegaly.
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4. Bone pain.
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Dacrocytes
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5. Sweet syndrome : Extramedullary hematopoiesis in the skin.

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Note : Splenomegaly Mild/absent : Essential thrombocytosis.

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Moderate : PCRV.
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Massive : PMF, CML.

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Treatment :
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• Bone marrow transplantation.

• If unfit : Ruxolitinib.

Essential Thrombocytosis (ET) 00:17:26

Clinical Presentation :
• 50 to 60 y; Male = Female. • Risk of AML,
• Thrombosis +/- splenomegaly. extra-medullary hematopoiesis : Nil.
• Bleeding may be present • Prognosis : Good.
(D/t Acquired vWD).

Laboratory Investigations :
• Platelet count >4,50,000 (Incidental finding) : Rule out reactive thrombocytosis.
• Large mature platelets.
• Staghorn megakaryocytes : Giant cells with hyper-lobulated nucleus &
mature cytoplasm.
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Note : ----- Active space -----

• Giant megakaryocyte : Idiopathic thrombocytopenic purpura.
• Dwarf megakaryocyte : CML.
• Cloud megakaryocyte : PMF.
• Small platelet : Wiskott-Aldrich syndrome.

Treatment :
Aspirin If >60 yrs/evidence of thrombosis Add Hydroxyurea > IFN α.

Note : Anagrelide ↑ risk of leukemia (Discontinued in Rx of ET).

Pancytopenia 00:20:50

Bone marrow failure syndromes :

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Aplastic anemia. Myelodysplastic syndrome Pure Red Cell Aplasia Secondary myelofibrosis

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(MDS). (PRCA). (Secondary to drugs & toxin).

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Approach to Pancytopenia :
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Pancytopenia
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On bone marrow biopsy (Cellularity = 100 - Age)

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Hypocellular marrow Hypercellular marrow

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1. Aplastic anemia : Chronic course 1. AML/ALL : Acute course

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2. MDS (Hypocellular variants) 2. MDS

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3. Aleukemic leukemia 3. Megaloblastic anemia (Rare)

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4. PNH (Rare) 4. PMF

5. Hairy cell leukemia (Good prognosis)
6. PNH
7. Lymphoma with BM involvement
8. TB, SLE, HIV, sarcoidosis

Aplastic Anemia 00:24:56

Pancytopenia + hypocellular marrow.

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----- Active space ----- Etiology :

Inherited (Pediatric) : Acquired :
1. Fanconi’s anemia : 1. Idiopathic (M/C).
FANCA mutation (A/w polydactyly). 2. Non A-Non B-Non C hepatitis virus.
2. Dyskeratosis congenita (DC) : 3. Drugs Chloramphenicol.
Telomerase repair complex defect. NSAIDs.
3. Shwamann-Diamond syndrome d-Penicillamine.
(Ribosomopathy) : 4. Eosinophilic fasciitis
Pancreatic malabsorption + (Scleroderma mimic).
BM failure.

Clinical Presentation :
• Age at presentation : >60 yrs. • Fatigue.
• Very poor prognosis. • Profound neutropenia :

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• Bleeding (M/C) : ↑ risk for invasive aspergillosis.

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(Well-preserved patient).
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Treatment :
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• TOC : Allogeneic Hematopoietic Stem Cell Transplant (AHSCT).

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• If unfit : Equine Anti-thymocyte Globulin (e-ATG) + cyclosporin.

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Pure Red Cell Aplasia

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00:30:08
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Gene mutation : RPS-19.

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Associations Diamond-Blackfan syndrome.

Hereditary spherocytosis + Parvo B19 (Giant proerythroblast) Aplastic crisis.
Thymoma/CLL.

Myelodysplastic Syndrome (MDS) 00:31:16

Presentation :
• Worldwide : >60 yrs.
• India : 40-60 yrs (M/C : 5q deletion MDS; Female > Male).
- Good response to lenalidomide.
• Anemia (M/C) : Macrocytic > Microcytic.

Pathogenesis :
Myeloid cell dysplasia Ineffective myelopoiesis Pancytopenia.

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Laboratory Investigations : ----- Active space -----

BM biopsy : Hypercellular > hypocellular marrow.
Cells on peripheral smear :
• RBC : Ringed sideroblast.
Megaloblast.
Macrocytic normoblast. Ringed sideroblast
• WBC : 5 to 19% blast cells (↑ risk of ALL).
Pseudo Pelger Huet cells (<2 lobes in nucleus).
Dohle bodies.
Toxic granules.
• Platelets : Pawn ball megakaryocytes.
Treatment : Pseudo Pelger Huet cells
• Trilineage involvement (M/C) :

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- AHSCT.

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- If unfit Hypomethylating agents :
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Azacitidine, decitabine.
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• Single lineage involvement :

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- 5q deletion + : Lenalidomide.
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Pawn ball megakaryocyte

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- 5q deletion - : EPO.
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• Luspatercept (New drug) : Inhibits SMAD signalling pathway.

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Plasma Cell Dyscrasias

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00:37:25
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Pathogenesis :
Marginal zone Memory B-cell
Germinal centre
B-cell Activated B-cell Plasma cell (Polyclonal : Different Ab light chains κ/λ)
if monoclonal
Plasma cell tumor/dyscrasia
• IgG κ/IgG λ (M/C) : M component.
Types :
1. Multiple myeloma. 3. Amyloid Light chain (AL) amyloidosis.
2. Waldenstrom macroglobulinemia. 4. Heavy chain disease.
Types of monoclonal gammopathies :
Monoclonal Gammopathy of Smoldering myeloma Multiple
Undetermined Significance (MGUS) (Asymptomatic myeloma) myeloma
M protein concentration <3 g/dL ≥3 g/dL ≥3 g/dL
BM plasma cells <10% ≥10% ≥10%
Myeloma defining event Absent Absent Present
Note : Risk of transformation of MGUS to myeloma 1%.
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----- Active space ----- MULTIPLE MYELOMA

Myeloma defining events : (Any one)
Mnemonic : SLiM CRAB
1. Sixty : ≥60% BM plasma cells. 5. Renal failure : Creatinine >2 mg/dL.
2. Light chain ratio : κ/λ or λ/κ >100. 6. Anemia : Hb <10g/dL.
3. MRI : At least one focal lesion. 7. Bone lytic lesions ≥1.
4. Hypercalcemia : >11 g/dL.

Diagnosis of myeloma : 1 out of 7 events + M-protein + BM plasma cells.

Investigations :
• Serum protein electrophoresis (SPEP) +
Followed by
Serum immunoelectrophoresis (SIFE) + BM biopsy.
Serum Free Light Chain ratio (SFLC)
• Flow cytometry + CD 38; CD 138.

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M-spike
- CD 19.

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Note : SPEP alone Less specificity (67%). gm
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Serum protein electrophoresis

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High risk for MM : Very poor prognosis.

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1. Deletion 17p. 3. t(14; 20).

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2. t(14; 16). 4. t(4; 14).

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Clinical presentation :
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1. Age >70 yrs.

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2. Anemia + ↑ ESR + reversal of A:G ratio.

3. Hypogammaglobulinemia : ↑ risk of infections (Recurrent pneumonia/UTI).
4. Acute Kidney Injury (AKI).
5. Radiculopathy.
6. Bone pain and/or unexplained fracture.

Treatment :
Low/moderate risk :
(Bortezomib + Dexamethasone + Lenalidomide) x 3 cycles
Followed by
Autologous stem cell transplant.
(Non-curative)
High risk MM : Replace bortezomib with carfilzomib.

• New drug : Daratumumab (CD38 monoclonal antibody).

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Waldenstrom Macroglobulinemia 00:52:20 ----- Active space -----

• AKA Lymphoplasmacytic lymphoma (Misnomer).

• Lymphoplasmacytic cells proliferation in BM : IgM bearing memory B-cell.
• Myd 88 mutation +.

Presentation :
• No lytic or renal lesions.
• IgM related hyperviscosity symptoms Cryoglobulinemia.
Cold agglutinin disease.
Treatment : Plasmapheresis.

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----- Active space ----- HEMATOLOGY REVISION - 4

B-cell Maturation & Neoplasms 00:01:00

In bone marrow :
Common lymphoid progenitor CD34, HLA DR

Pro-B cell CD19, CD34, HLADR

Pre-B cell CDIO (CALLA antigen), TdT : Specific markers of Pre-B cell.
B-cell markers : CD19, CD20, CD21, CD22, CD79a, CD79b

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Immature B-cell. B-cell markers, SIgM (Surface IgM)

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Note : Precursor B-cell ALL Pro-B ALL (Acute lymphoblastic leukemia).
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Pre-B ALL (M/C) :

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• Overall best prognosis in child.

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• Early pre B cell ALL : Best prognosis in child.

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Immature B cell ALL.

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In blood & lymph nodes :

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Immature B cell released into blood

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Naive B cell B cell markers, S IgM, CD5 +/-

Majority Few

Blood Lymph node (Interfollicular area), acquires SIgD

Few Majority
Apoptosis
If failed Pre-germinal centre Germinal/Activation/
(Mantle zone) Maturation centre
Monoclonal naive B cell expansion
Mantle cell lymphoma • Diffuse large B-cell
Chronic lymphocytic leukemia
B-cell markers, SIgM, lymphoma (DLBCL) (M/C)
B-cell markers, SIgM, CD5, CD23 SIgD, CD5, Cyclin D1 • Burkitt’s lymphoma
• Follicular lymphoma

B-cell markers, SIgM, SIGD,

CD10, CD23, BCL-6

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In germinal centre : ----- Active space -----

Germinal centre B-cell B-cell markers, SIgM, SIgD

ABC DLBCL Activated B-cell/ Marginal zone Marginal zone

(Poor prognosis) Plasmablast (Post germinal centre) lymphoma

Plasma cell Only CD19, CD38, CD138 Memory B cell.

(Polyclonal) No additional markers
(Loses CD19 Monoclonal) • Small lymphocytic lymphoma (SLL).
Plasma cell dyscrasias : • Waldenstrom macroglobulinemia.
• Multiple myeloma. • Hairy cell leukemia (HCL).
• Heavy chain disease. • Hodgkin’s disease.
• AL Amyloidosis.

T-cell Neoplasms 00:19:30

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Precursor T-cell Leukemia/Lymphoma (T-cell ALL) :
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Few cells proliferate in thymus Mediastinal widening Respiratory symptoms.
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(Hence lymphoma)
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Mature 7-cell neoplasms :

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1. Cutaneous T-cell lymphoma : AKA mycosis fungoides/Sezary syndrome.

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2. Anaplastic large cell lymphoma : A/w breast implants, markers CD30 + &
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ALK + .
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3. Angio immunoblastic lymphoma : Midline deformities + .

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4. Large granular lymphocytic leukemia : A/w rheumatoid arthritis (Usually

benign).
5. Enteropathic T-cell lymphoma : A/w celiac disease.
6. Extranodal NK/T-cell lymphoma : Presents as nasal mass.
7. Adult T-cell leukemia/Lymphoma : A/w HTLV I.

Causative Agents of Neoplasms 00:22:40

A. Ebstein-Barr Virus (EBV) :

1. Hodgkin’s disease (Classical) : 2. Burkitt’s lymphoma
100/70/40/20 rule 100% : Child.
100% Lymphocyte depleted. ~ 75% : Adult.
70% : Mixed cellularity 3. Primary CNS lymphoma.
40% : Nodular sclerosis 4. Post transplant lymphoma.
20% : Lymphocyte rich. 5. Extranodal NK/T-cell lymphoma.

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----- Active space ----- B. Human Immunodeficiency Virus (HIV) :

1. Diffuse large B-cell lymphoma (DLBCL).
2. Burkitt’s lymphoma.
C. H. pylori MALToma :
M/c extronodal marginal zone lymphoma.
D. HHV 8 :
1. Primary effusion lymphoma.
2. Castleman’s disease.
E. HTLV 1 : Adult T-cell leukemia/Lymphoma.
F. HCV :
1. Waldenstrom macroglobulinemia.
2. Splenic marginal zone lymphoma.

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Note : Non-classical Hodgkin’s : No EBV association.

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Acute Lymphoblastic Leukemia (ALL) 00:26:30
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B-cell ALL (M/c) T-cell ALL

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• Pro B-cell ALL

Significant Precursor T-cell ALL
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• Pre B-cell ALL

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• Immature B-cell ALL

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• Children <10 yrs (Excellent prognosis)

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Mostly adolescent
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Age group • Adolescents (Good prognosis)

(Poor prognosis)
• Adults > 60 yrs (Poor prognosis)
Mediastinal widening Presentation Bone marrow involvement Mediastinal widening

Diagnosis :
Clinical presentation of B-cell ALL :
• Bone pain
D/t ↑ proliferation in bone marrow (BM).
• pancytopenia
• Involvement of CNS, testes D/t ↑ blast cell dissemination
• Hyperviscosity of blood (High count phase).
Blasts in bone marrow
Morphology : ≥20% blasts in marrow.
Cytology : PAS, Acid phosphatase + .
Immunophenotyping : CDIO; tdt.

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Note : ----- Active space -----

• Myeloblasts have Nucleolus.
Larger cell size.
Auer rods.
MPO & Sudan black staining + .
Prognostic Factors :
Good prognosis Bad prognosis.
Race White Black
Age 2-9y <1 or >1o yrs
Sex Female Male
CNS involvement - +
Hepatosplenomegaly,
- +
Lymphadenopathy

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Mediastinal mass - +

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Testicular involvement - gm +
Type L1 L2, L3
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Cytogenetics Hyperdiploidy Hypodiploidy

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Immunophenotype B-cell early Pre-B-cell T-cell

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Translocation t(12;21) t(9;22) ; t(4;11) ; t(1;19)

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Genes Notch 1 gene

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Treatment :
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1. Induction phase : (Main phase)

• To achieve minimal residiual disease (MRD) negative (<0.01% blasts in BM).
• Drugs used :
- Steroids (DOC).
- L. asparginase : Used in children, minimal use in adult d/t S/E.
- Vincristine : In hyper CVAD regimen for adults (+ Cyclophosphamide,
Adriamycin, Dexamethasone).
- Daunorubicin.
- High dose methotrexate (MTX) : In adult & child ALL.
Note : High dose MTX is also used in osteosarcoma.
• If remission not achieved at the end of cycle : Blinatumomab (C19 & CD23
antagonist).
2. Consolidation : 2 cycles given once MRD negative.
3. Maintenance : Oral MTX & 6-mercaptopurine (6-MP) for 2 years.

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----- Active space ----- Chronic Lymphocytic Leukemia 00:38:50

Pathogenesis :
Failure of apoptosis of naive B-cell + CD5 & CD23 Monoclonal expansion of naive
B-cell (>5000 cells/μL).
Note : If monoclonal expansion in lymph node SLL.

Diagnosis :
Diagnosed incidentally on routine check-up.
Population at risk : 65 to 85y ; Male > Female.
Blood picture : Small, blue,
• TLC : 70,000 to 80,000 cells/μL. round lymphocyte,
• Absolute lymphocyte count : ↑↑↑. pale cytoplasm
• Hb & platelet count : Normal.
Smudge cells

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Rai & Binet staging : Peripheral smear : Lymphocytosis

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• Stage 0 : Only lymphocytosis.
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• Stage 1 : Lymphocytosis + lymphadenopathy.
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Prognosis :
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Good prognosis : Deletion 13q, hyperdiploidy & mutated Ig heavy chain.

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Poor prognosis : Zap70 expression, b2 microglobulin & unmutated Ig heavy chain.

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Treatment :
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Most cases do not require treatment.

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Indications for treatment :

1. Development of B-symptoms : Fever, night sweats, weight loss.
2. Lymphadenopathy, hepatosplenomegaly.
3. BM involvement.
4. Richter's syndrome : Low grade tumor (CLL/SLL) High grade tumor
(DLBCL).
5. Autoimmune hemolytic anemia (Warm AIHA).

Drugs used :
• FCR regimen (Fludarabine, Cyclophosphamide, Rituximab) : Not fit for elderly.
• BR regimen (Bendamustine, Rituximab) : Preferred regimen.
• If relapse occurs/unfit for above regimen :
- Ibrutinib : Tyrosine kinase inhibitor.
- Venetoclax : BCL2 inhibitor.
- Idelalisib : Pi3k inhibitor.

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Lymphomas 00:46:43 ----- Active space -----

Grade of tumor :
Low grade High grade
• Follicular lymphoma • DLBCL (M/c)
• Marginal Zone Lymphoma (MZL) • Burkitt's lymphoma
• Hairy cell leukemia • Mantle cell lymphoma (MCL)
• SLL
• Waldenstrom macroglobulinemia
Common clinical presentation :
1. Age : >60y (Except Burkitt's 5. Asymptomatic lymphadenopathy.
lymphoma : In children). 6. Extranodal involvement :
2. Sex : Male > Female (Except MZL). - GIT (M/c).
3. B-symptoms less common. - Waldeyer's ring.

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4. Non-contiguous involvement. - Oropharynx.

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Mantle Cell Lymphoma :
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Extranodal involvement :
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• Aggressive tumor (Most aggresive : Non-nodal subtype) :

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- BM involvement. - Waldeyer's ring involvement.

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- GIT involvement. - Lymphomatoid polyposis.

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Imnumophenotyping :
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• CD5 + , Cyclin D1 + . • CD10 - , CD23 - .

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Translocation : t(11; 14).

Prognosis : SOX11 upregulation (Good prognosis).
Note : R-CHOP regimen (Used in Non-Hodgkin's lymphoma) inadequate for MCL.
Follicular Lymphoma :
Low grade : May undergo spontaneous remission.
Immunophenotyping : CD10, CD23, BCL-6 & aberrant BCL-2.
Translocation : t(14;18) (Ig heavy chain gene Chr 14 & BCL Chr 18).
Treatment :
• Low grade : Rituximab (DOC). • Advanced : R-CHOP regimen
Marginal Zone Lymphoma :
Prevalence : Females > Males d/t autoimmune association.
Extranodal involvement :
• GIT : MALToma (A/w non-atrophic • Salivary gland : A/w Sjogren's
pangastritis of H. pylori). syndrome.
• Spleen : A/w HCV.
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----- Active space ----- Immunophenotyping :

• Positive : B cell markers, S. IgM, S. IgD.
• Negative : CD5, CDIO, CD23.
Translocation : t(11;18).
Treatment : Responds to H. pylori therapy.
DLBCL :
Clinical presentation :
• Rapid enlargement of lymphnodes B-symptoms & compression symptoms.
• BM involvement +/-.
• Extranodal involvement : Primary CNS lymphoma, effusion lymphoma, body
cavity lymphoma.
Immunophenotyping :
Germinal centre DLBCL (Good prognosis) > ABC-DLBCL (Poor prognosis)

om
MUM 1 antigen +

l.c
CD10, CD23, BCL-6, aberrant BCL-2
ai
gm
Prognosis : Poor prognosis seen in :
@

• Double hit lymphoma : BCL-2 or BCL-6 + high grade lymphoma &

60
23

• Triple hit lymphoma : BCL-2 and BCL-6 rearrangement of c-myc.

ik
hv

Treatment : R-CHOP regimen.

rit
|

Burkitt's lymphoma :
w
ro

• Ki 67 +++ : High proliferation index.

ar
M

• Chemosensitive.
©

Varieties :
Age A/w EBV Presentation
Endemic Child 100% Jaw/axillary mass
Sporadic Adult 70% Abdominal mass
Translocation :
• t( 2;8), t(8;14), t(8;22).
• C-myc is on chromosome 8.
HPE : Starry sky appearance (Star : Macrophages, sky : Tumor cells).
Hairy Cell Leukemia :
Bone marrow.
Memory B-cells BRAF-1 mutation Hairy cells
Spleen.
Presentation : Pancytopenia + Massive splenomegaly.
Immunophenotyping : CD11C, CD25, CD103, CD123, TRAP + , Annexin + .
Bone marrow biopsy : Fried egg appearance + fibrosis.

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 Hematology Revision - 4 117

Complications : Increased risk of infection d/t neutropenia + monocytopenia. ----- Active space -----
• Atypical mycobacterial infection.
• Aspergillus infection.
Treatment : Cladribine (or) Pentostatin.

Hodgkin's Disease 01:03:40

Pathogenesis :
Aberration of PDL1 gene
Memory cells Reed sternberg cell (RS cell) in appropriate
inflammatory background.
Hodgkin's disease v/s Non-Hodgkin's lymphoma :
Hodgkin's disease Non-Hodgkin's lymphoma
Age 15-34y (Bimodal peak) Elderly
Contiguous Contiguous Non-contiguous

om
Disease Nodal disease :

l.c
Mostly extranodal
node Posterior cervical > supraclavicular > axillary
ai
gm
B-symptoms More common Less common
@
60

A/w EBV More Less

23
ik

Classification :
hv
rit

Types RS cell EBV + Other features

|
w

Classical Hodgkin's disease : CD15 + , CD30 +

ro
ar

Lymphocyte rich Scanty 20% Good prognosis

M
©

• M/C type in the world

Nodular sclerosis Lacunar 40% • M/C in females
• Mediastinal involvement +
• A/W HIV
Mixed cellularity Classical 70% • M/c in India
• Seen in children & elderly
Lymphocyte depleted Absent 100% A/W HIV
Non-classical Hodgkin's disease : CD20 +
Lymphocyte predominant Popcorn EBV - C/F : Enlarged node in axilla

Treatment :
Classical Hodgkin's disease :
• ABVD regimen (Adriamycin, Bleomycin, Vincristine, Dacarbazine).
• If no response in first phase : Brentuximab (Anti-CD30).
Non-classical Hodgkin's disease : Radiotherapy is sufficient.

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 118

----- Active space ----- ENDOCRINOLOGY REVISION - 1

Classification of Hormones  00:05:04

BASED ON STRUCTURE
Hormones Features
Amino acid derivatives
T3, T4 -
Tyrosine Catecholamines :
Adrenaline (Major), Produced by : Adrenal medulla
Noradrenaline, Dopamine
Produced by :

om
Tryptophan • Enterochromaffin cells of

l.c
Serotonin
(Neurotransmitter GIT (Main).
ai
gm • Raphe nuclei of brainstem.
action)
@

Melatonin Produced by : Pineal gland

60
23

Vitamin derivatives
ik
hv

• Vitamin A
-
rit

• Vitamin D
|
w

Peptide hormones
ro
ar

• Posterior pituitary hormones

M

Small • Hypothalamic hormones <50 amino acids

©

• ACTH
GH 191 aa
Large
Prolactin 199 aa
(>50 aa)
Insulin, Parathormone, Renin -
Glycoproteins FSH, LH, TSH -
Steroid hormones
Produced by :
1. Aldosterone 1. Zona glomerulosa
Adrenal cortex 2. Cortisol 2. Zona fasciculata
hormones 3. Adrenal androgens : 3. Zona reticularis
• DHEAS (M/C).
• Androstenedione (2nd M/C)
Testosterone, estrogen,
Sex steroids -
progesterone
DHEAS : Dihydroepiandrosterone sulphate.

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 Endocrinology Revision - 1 119

BASED ON MECHANISM OF ACTION ----- Active space -----

Receptor Examples Property

1. Type 1 : Cytoplasmic • Adrenal cortical hormones • Signals mediated by :
(Homodimeric receptor) • Sex steroids Receptor hormone complex
• Effector action :
Gene transcription
• Vitamin A • Hormone features :
Group 1 2. Type 2 : Nuclear
• Vitamin D - Lipophilic (Require
(Intracellular (Heterodimeric receptor)
• Thyroid hormones transport protein)
receptors)
- Longer t1/2
• SF 1
Constitutive action without a
Orphan receptors • DAX 1 Gonadotrophs
ligand.
• HNF4a : MODY type 1
GPCR • Signal mediated by :
TKR Insulin, growth factors Second messenger
(Tyrosine kinase receptor) (Eg : TGF-a) • Effector action :

om
Group 2
Protein translocation or

l.c
(Cell JAK
Twin hormones protein channels
ai
membrane (Janus kinase aka cytokine gm
(GH, PRL), EPO • Hormone features :
receptors) receptors)
@

- Hydrophobic (Transport
60

Serine threonine kinase Inhibin, activin, BMP-7, protein not required)

23

receptors TGF-b - Shorter t1/2

ik
hv
rit

G-Protein Coupled Receptors & their Secondary Messengers :

|
w
ro

cGMP IP3 /DAG cAMP

ar
M

Receptor type Gt Gq Gs /Gi

©

Vasoconstriction via Protein phosphorylation via

Action Vasodilation
Ca2+-calmodulin pathway & PKC cAMP-PKA pathway
• Hypothalamic : CRH
• Angiotensin II • Anterior pituitary :
• Substance P FSH, LH, TSH, ACTH
• Hypothalamic : TRH, GnRH • Posterior pituitary :
Hormones NO, ANP • Posterior pituitary : V2 receptor
V1 & V3 receptors, oxytocin • GIT : S ecretin, glucagon,
• GIT : CCK, gastrin somatostatin, PTH,
• ANS : a1 , Ach receptor calcitonin
• ANS : a2 , all b receptors
Note :
• Only α2 and somatostatin act via Gi (↓cAMP).
• NO and ANP vasodilation occurs d/t cGMP.

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 120 Medicine

----- Active space ----- Pituitary Gland 00:24:38

Anatomy :
Anterior pituitary : Oral ectoderm (Rathke’s pouch).
Posterior pituitary : Neuroectoderm (Floor of 3rd ventricle).

Note : Pituitary insufficiency rarely causes

hypothyroidism (20% TSH release in extra pituitary)

Prone to vascular injury

Prone to mass effect
Transcription Factors :
Transcription Factors Cells Hormones Produced
Somatotrophs
GH
1. Prop-1 > pit-1 (Most abundant)

om
(M/C cause Mammotroph/Lactotroph

l.c
PRL
for congenital (Last cell to appear)
ai
hypopituitarism)
gm
Thyrotrophs
TSH
@

(Least abundant)
60
23

POMC (Proopiomelanocortin)
ik

derivatives :
hv
rit

• ACTH
|

Corticotrophs • MSH
w

2. T-pit
(1st cell to appear) • β-lipotropins
ro
ar
M

Endorphins
©

(Natural painkillers)
Gonadotrophs
3. GATA-3 (SF-1, DAX-1) FSH, LH
(Produced throughout gland)
Acidophilic cells Basophilic cells
Note :
• ↑ACTH is a/w ↑MSH Hyperpigmentation.
• Hormones of happiness (DOSE) : Dopamine, Oxytocin, Serotonin, Endorphin.

Hypothalamo-hypophyseal Relation :
Hypothalamus acts on :
• Anterior pituitary : Via hypothalamo-hypophyseal portal system &
superior hypophyseal A.
• Posterior pituitary : Via axonal-neuronal connection through the stalk.
- Blood supply : Inferior hypophyseal A.
- Storage of hormones : ADH (Supraoptic & paraventricular nucleus)
Oxytocin (Periventricular nucleus).
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 Endocrinology Revision - 1 121

Note : ----- Active space -----

CA breast mets (M/c) reach post. pituitary via inferior hypophyseal A. leads
to
DI.

PITUITARY TUMORS
M/C tumors : Prolactinoma > GH-secreting adenoma > ACTH-secreting adenoma.
Effects :
1. ↑Hormone release : Functional tumors (Prolactinoma).
2. Stalk effect : Hypopituitarism
Loss of hypothalamo-hypophyseal connection Hyperprolactinemia
3. Mass effect : Central DI
• ↑ICT.
• Optic chiasm compression Heteronymous/bitemporal hemianopia.
• Cavernous sinus thrombosis, VIth nerve palsy.
Ix :

om
T1 -weighted MRI :

l.c
ai
Tumor displacing stalk gm
@

Bright
60

spot
23
ik
hv
rit

Sagittal section MRI: Normal pituitary

|
w

Prolactinoma 00:45:35
ro
ar
M

Serological Interpretation :
©

PRL values
Inference Etiology
(μg/L or ng/ml)
<25 Normal value -
REM sleep/stress/chest wall
25-40 Physiological ↑
stimulation/pregnancy (Upto 180 mcg/L).
• Typical antipsychotics, Risperidone,
TCA, SSRI, metoclopramide.
Drugs
• Opiates, verapamil, H2 blockers,
40-100 α-methyldopa.
Hormones Estrogen, TRH, VIP, oxytocin.
Systemic conditions CKD, CLD, PCOS.
Suspect tumor -
Macroprolactin
No tumor
>100 (Inactive prolactin)
Hook effect
Tumor present
(↑PRL seen only on serial dilution)
>200 Tumor confirmed -
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 122 Medicine

----- Active space ----- Types of Tumors :

Microadenoma Macroadenoma
> 1 cm
Size <1 cm
> 4 cm : Giant adenoma
Incidence M/C Less common
F:M F>M F=M
Clinical Presentation :
Based on age :

>25 yrs (M/C) <25 years (Genetic cause)

• MEN 1
• Carney’s complex Note : Acromegaly in <20 years,
suspect the same causes.

om
• McCune-Albright

l.c
- Cafe-au-lait spots
ai
gm
- Polyostotic fibrous dysplasia
@

- Precocious puberty
60
23

- Tumors
ik
hv

Based on sex :
rit
|

In females :
w
ro

Galactorrhea-amenorrhea complex :
ar
M

↑PRL Inhibits hypothalamopituitary gonadal axis Hypogonadism

©

2˚ amenorrhea, infertility, hot flushes

In males :
Late presentation d/t giant adenoma (>4 cm).
• Stalk effect, mass effect.
• Loss of libido, erectile dysfunction (Rare).

Investigations :

Screening test : Fasting PRL.

IOC : Gadolinium-enhanced MRI.
• Microadenoma :
Hypointense (No contrast).
• Surrounding pituitary gland :
Hyperintense (Contrast uptake).
Gd enhanced MRI MRI
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 Endocrinology Revision - 1 123

Treatment : ----- Active space -----

Medical Mx : 1st line.
Drugs :
Dopaminergic agonist :
• Cabergoline (DOC) • Bromocriptine (Pregnancy DOC).
- S/E : TR, ILD seen at dose >2mg.
Rx protocol :

Asymptomatic Symptomatic
(Incidental detection)
After 3-6 months Cabergolin 0.25mg twice weekly
Follow up MRI Follow up after 1 month
Check size Check S. PRL levels

om
Size ↑↑ No increase

l.c
↓↓ S. PRL ↑↑ S. PRL ↑↑ S. PRL with
ai
gm
Medical Rx as No Rx S/E of drug
@

Complete ↑Cabergolin upto

60

symptomatic
23

Rx for 2 yrs 2mg twice weekly Dopamine agonist

ik
hv

Surgical Mx : (Max dose) resistance

rit

If S/E +ve
|

Indications :
w
ro

1. Dopamine agonist resistance (20%).

ar
M

2. Pituitary apoplexy.
©

3. Pregnancy (Refractory to 4 weeks bromocriptine).

4. Persistence of compression symptoms.
Surgery : Trans-sphenoidal tumor resection/hypophysectomy.

Growth Hormone 01:02:41

PHYSIOLOGY
Comparative Features with PRL :
GH PRL
Stimulators
Sleep stage N2 , N3 of NREM REM
Others Hypoglycemia, ghrelin, GHRH Estrogen, TRH, oxytocin
Somatostatin, obesity,
Inhibitors Dopamine
malnutrition (GH resistance)

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 124 Medicine

----- Active space ----- Screening Test :

• IGF + IGFBP-3 levels (t1/2 12-15 hrs).
- GH levels not used (D/t short t1/2 & pulsatile release).

Effects :
Mechanism :
1. Direct.
2. Indirect : Via somatomedin-C/IGF-1 (Produced in liver)

Peripheral actions.
Site of action :
GH IGF-1
Epiphyseal growth (Bone) + +
Adipose tissue Lipolysis Anti-lipolytic

om
Muscle protein synthesis + +

l.c
ai
Salt and H2O retention gm + -
@

Carbohydrates Diabetogenic Anti-diabetogenic

60

GH actions independent of IGF-1 : Mnemonic BEAMS

23
ik
hv

Note : Thyroid hormone & testosterone produce IGF-1 independent of GH.

rit
|

ACROMEGALY
w
ro

Etiology :
ar
M

GH secreting Pituitary adenoma (98%) :

©

• Macroadenoma (M/C).
• 20% a/w ↑PRL : Somatomammotrophic adenoma.
• Densely granulated & sparsely granulated types
(Poor prognosis).
Ectopic : Pancreatic islet cell tumor.
GHRH secreting Hypothalamic tumor : Hypothalamic hamartoma.
Ectopic : Bronchial carcinoid.
Clinical Presentation :
Sex : M > F.
Age : >40 years (M/C).

On examination :
1. Coarse facies : Thickening of lips, tongue, & face + Frontal bossing + Prominent
supraorbital ridge
2. Acral enlargement.
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 Endocrinology Revision - 1 125

----- Active space -----

Acral enlargement Frontal bossing Coarse facies

Complications :
System/structure Complication
Nerve Entrapment neuropathy
Muscle Myopathy
• Hypertriglyceridemia.
• Hypercalcemia (D/t 1-α-hydroxylase)
Metabolic Hypercalciuria Stones.

om
• Hyperphosphatemia.

l.c
• Diabetes (Uncontrolled, short duration).

ai
gm
Ophthalmic Angle closure glaucoma
@

Respiratory OSAS, PAH

60
23

• M/C cause of death.

ik

• Asymmetrical LVH Heart failure with preserved EF.

hv

CVS
rit

• ↑incidence of CAD.
|

• HTN.
w
ro

Thyroid Goiter
ar
M

GIT Colonic polyps (Non-malignant)

©

Renal Salt & H2O retention

Menstrual Menstrual abnormality (M/C : Oligomenorrhea)
Joints Arthralgia
Skin Seborrhea
Indicators of high activity mnemonic : DOSA

Management :
Investigations :
1. Screening : IGF-1 levels.
2. Confirmatory :
Glucose-induced GH suppression test.
- GH <1 ng/mL : Normal.
- GH >40 ng/mL : Poor prognosis.
3. IOC : Gd enhanced MRI Heterogenous enhancement
(Heterogeneous enhancement of macroadenoma
d/t macroadenoma).
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 126 Medicine

----- Active space ----- Surgical Mx :

Transsphenoidal surgery (TOC) followed by immediate post-op GH :
• Undetectable : Good prognosis.
• Detectable Risk of relapse Medical Mx initiated Repeat imaging
after 12 weeks.
Medical Mx :
Drugs :
1. Somatostatin receptor ligands : DOC
- Octreotide.
- Lanreotide.
- Pasireotide.
2. Bromocriptine.
3. Cabergoline.
4. GH receptor antagonist : Pegvisomant.

om
l.c
Relapse after medical management :
ai
gm
• Fit for surgery : 2nd surgery done.
@
60

• Unfit for surgery : Gamma knife stereotactic RT.

23
ik
hv
rit
|
w
ro
ar
M
©

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 Endocrinology Revision - 2 127

ENDOCRINOLOGY REVISION - 2 ----- Active space -----

Acquired Hypopituitarism 00:00:06

Etiology :
1. Stalk effect : Hypopituitarism + ↑ PRL + Central DI.
Cause M/c examples
• Functional : GH secreting.
Tumor
• Non-functional : Rathke cleft cyst, Craniopharyngioma.
Infiltration Langerhans cell histiocytosis, Sarcoidosis, Hemochromatosis
Trauma/surgery -

om
Infection TB, HIV, Histoplasmosis, Toxoplasmosis

l.c
ai
2. Lymphocytic hypophysitis. gm
@

3. Sheehan’s syndrome.
60

4. Empty sella syndrome : 1°, 2°.

23
ik

5. Viper bite.
hv
rit

Clinical Features :
|
w
ro

Hormone deficiency Effect

ar
M

Central pituitary hormones :

©

• Asthenia, weight loss, loss of appetite.

• Repeated episodes of hypoglycemia/hypotension.
ACTH • Euvolemic hyponatremia.
• Eosinophilia.
Note : Cushings syndrome Eosinopenia.
TSH (Rare) Cold intolerance, constipation, bradycardia.
Lateral pituitary hormones :
PRL Only significant in lactating mothers.
Centripetal obesity, hypertriglyceridemia,
GH
endothelial dysfunction.
Gonadotropins (All over the gland) :
Hypogonadism features :
• Muscle wasting, disproportionate fracture.
FSH, LH
• In males : Loss of libido.
• In females : Irregular cycles, hot flushes, 2° amenorrhea.
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 128 Medicine

----- Active space ----- Investigations :

Direct measurement : FSH, LH, TSH, PRL.
Indirect measurement :
• IGF-1.
• GH provocation test with Glucagon, GH assessment.
L-dopa, Arginine, Clonidine.
• Insulin tolerance test : Gold standard method.

Pituitary Apoplexy & Differentials 00:10:08

Pituitary Apoplexy :
Acute intrapituitary hemorrhage.
Etiology :
1. Tumor (Adenoma).

om
2. Necrosis (Sheehan syndrome).

l.c
3. Normal gland :
ai
gm
- Risk factors : DM, HTN, sickle cell anemia.
@
60

Clinical features :
23

• Progressively worsening headache ± meningeal NCCT : Pituitary apoplexy

ik
hv

signs ± ophthalmoplegia.
rit

• Severe hypotension, hypoglycemia.

|
w
ro

Management :
ar
M

Pulse steroid therapy : 1st dose Methylprednisolone 500 mg.

©

F/b
Surgical decompression.
Differentials :
1. Sheehan’s syndrome.
2. Lymphocytic hypophysitis.
3. Empty sella syndrome.

Sheehan’s syndrome vs Lymphocytic hypophysitis :

Sheehan’s syndrome Lymphocytic hypophysitis
Postpartum ischemic necrosis of the Postpartum inflammatory mass : IgG4
Etiology
pituitary gland (D/t PPH, shock, DIC). containing lymphoplasmacytic cells.
• Hypogonadism. • Stalk effect.
Effects
• ACTH failure. • Mass effect.
Hormonal • Anterior pituitary hormones : ↓. • PRL↑.
profile • ADH : Normal. • ADH ↓.

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 Endocrinology Revision - 2 129

Sheehan’s syndrome Lymphocytic hypophysitis ----- Active space -----

• Immediately post-delivery :
Lactational failure. • Pituitary enlargement.
• 3-6 months post delivery : • Headache, visual disturbances.
Clinical - Lactational failure. • Hypopituitarism.
features - 2° amenorrhea, breast atrophy, • Hyperprolactinemia.
↓ libido, genital & axillary hair loss. • Associated autoimmune disease.
- Signs of premature aging. • Diabetes insipidus.
- Asthenia & weakness.

Imaging

om
Necrosed gland Inflammatory mass

l.c
ai
Rx Complete hormone replacement. gm Responds to steroids.
@

Empty sella syndrome :

60
23

Primary Secondary
ik
hv

Tear in dura CSF collects As a part of necrosis/tumor

rit

Etiology
in sella. Empty sella.
|
w

Associated with Benign intracranial hypertension. Sheehan’s syndrome.

ro
ar

• Hypopituitarism absent. • Hypopituitarism present.

M

Clinical features
• Features of ↑ ICT.
©

Anti - Diuretic Hormone (ADH) 00:19:50

Stimuli for ADH Release :

1. Osmotic stimuli (Main) : ↑ Serum osmolality Thirst, ADH release.
2. Non - osmotic stimuli : ↓ Effective circulatory volume.

Note :
• Serum osmolality = 2 x Na+ + (Blood glucose/18) + (BUN/2.8).
- ↓ S. osmolality Hyponatremia.
• ↑ S. osmolality only in head injury & intubated patients Hypernatremia.

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 130 Medicine

----- Active space ----- Action of ADH on Vasopressin Receptors :

Location Effect
Blood Vasoconstriction, platelet aggregation
V1
Heart Myocardial thickening
(Via IP3/DAG pathway)
Liver Glycogenolysis
V2 Endothelium VWF release
(Via cAMP protein Cortical collecting duct
kinase A pathway) Free H2O reabsorption
(Via AQP2 on luminal side)
V3
Pituitary ↑ ACTH
(Via IP3/DAG pathway)

Note : AQP3 & AQP4 Present on basolateral membrane.

Hyponatremia 00:26:02

om
Disorder of water metabolism : ↑ water ↓ S. osmolality (D/t ↓ Na+).

l.c
Causes :
ai
gm
1. Excess ADH release.
@

2. Psychogenic polydipsia (Water consumption >15L/day).

60
23

3. Impaired solute reabsorption in thick ascending limb & DCT :

ik
hv

- M/c cause of CNS symptoms.

rit

- D/t diuretics (Thiazides > Furosemide).

|
w
ro

Grades of hyponatremia :
ar
M

S. Na+ (mEq/L) C/F

©

Very severe <100 ↑ ICT symptoms

Severe 100-119 CNS : Ataxia, confusion
Moderate 120-129 GIT symptoms, lethargy
Mild 130-134 Only GIT symptoms
Pseudohyponatremia :
Normal (285-290 mOsmol/kg) or ↑ S. osmolality with ↓ Na+.
Causes :
1. Translocational : D/t effective solutes (Glucose, mannitol, glycine, maltose).
2. Paraproteinemia.
3. Hypertriglyceridemia.
Approach to hyponatremia :
1. Rule out pseudohyponatremia.
2. Evaluate true hyponatremia (↓ S. osmolality) :
a. Rule out psychogenic polydipsia & diuretic overuse.
b. Evaluate causes for excess ADH.
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 Endocrinology Revision - 2 131

Causes for excess ADH ----- Active space -----

Appropriate Inappropriate
Hypovolemic Hypervolemic Euvolemic
Hyponatremia
hyponatremia hyponatremia hyponatremia
Low ECF volume : • SIADH.
• GIT loss : ↓ Urine Na+. • Thyroid & cortisol
• Renal loss : ↓ effective volume : insufficiency.
Etiology
↓aldosterone, CSW, D/t CCF, cirrhosis. Note : ↑ tonicity &
tubular injury. ↓ volume Normal
• 3rd space loss. ADH release.
SIADH (Syndrome of Inappropriate ADH) :
Causes :
1. Trauma (Head injury).
2. Drugs :
- Vincristine, oxytocin, NSAIDs.

om
- SSRIs, TCAs.

l.c
ai
- 5 Cs (Cyclophosphamide, Carbamazepine, Chlorpromazine, Clofibrate,
gm
@

Chlorpropamide).
60

3. Paraneoplastic syndrome (Small cell lung cancer, duodenal, thymic tumors).

23
ik

4. Acute intermittent porphyria.

hv
rit

5. Necrotizing pneumonia.
|
w

6. Meningoencephalitis.
ro
ar

Diagnostic criteria :
M
©

• ↓ S. osmolality.
• ↑ Urine osmolality.
• Euvolemia.
• ↑ Urine Na+ (>20 mEq/L, d/t ↑ natriuretic peptides & RAAS inhibition).
• Absence of hypothyroidism, hypocortisolism (Adrenal), pituitary, liver & renal
disease.
D/d : Cerebral Salt Wasting Syndrome (CSW).

CSW SIADH
Hyponatremia Hypovolemic Euvolemic
Head injury
Cause Head injury, drugs
Loss of adrenergic tone RAAS suppression
S. uric acid ↓ ↓↓↓<2 mg/dL
S. K+ ↑↑ N or ↑
Urine Na+ (Natriuresis) ↑

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 132 Medicine

----- Active space ----- Diabetes Insipidus (DI) 00:42:32

Updated names (February 2023) :

• Central DI AVP-d (Arginine vasopressin deficiency).
• Nephrogenic DI AVP-r (Arginine vasopressin resistance).

POLYURIA :
Diagnostic criteria : >3L/24h or >40 mL/kg/day.
Water diuresis (M/c) Solute diuresis
H/o DM, mannitol therapy, diuretic
Presentation Urine output : >7 L/24h
use, relieved urinary obstruction
U. osmolality
<300 >600
(mOsmol/kg)
Urine dipstick - +

om
Nocturnal craving

l.c
+ -
ai
for cold water gm
@

Urine specific gravity 1.010 -

60
23

Hypotonic Polyuria :
ik
hv

3 L/24h + Urine osmolality <600 mOsmol/kg.

rit

Causes : AVP-d, AVP-r, Psychogenic polydipsia.

|
w
ro

AVP-d AVP-r
ar
M

Pathophysiology Deficiency of AVP. Resistance to action of AVP.

©

• Stalk effect.
• Fibrosed receptors d/t IgG4,
• Genetic causes (AD > AR >
Sjogren’s, Sarcoidosis.
XLR).
• Drugs : Lithium, Demeclocyline
• Pregnancy.
Cisplatin, Foscarnet.
Note :
• Hypercalcemia,
Causes Wolfram syndrome/DIDMOAD
hyperuricemia, hypokalemia,
syndrome :
hyperoxaluria.
• AR.
• Sickle cell anemia (Occlusion
• Diabetes Insipidus,
of vasa recta).
Diabetes Mellitus,
• Pregnancy.
Optic atrophy, Deafness.

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 Endocrinology Revision - 2 133

Investigations : ----- Active space -----

Plasma copeptin assay : Has replaced water deprivation test.
Hypotonic polyuria
Unstimulated random plasma copeptin

>21.4 pg/mL ≤21.4 pg/mL

Nephrogenic DI/AVP-r. Arginine stimulation test :

Measure stimulated copeptin levels

≥3.8 pmol/L <3.8 pmol/L

Psychogenic polydipsia. Central DI/AVP-d.
Treatment :

om
1. Central DI :

l.c
ai
- Desmopressin 10-20 mcg intranasally. gm
- Desmopressin 0.1-0.8 mg orally OD.
@
60

2. Peripheral DI : Thiazides (DOC)

23
ik

3. Lithium induced DI : Amiloride/Triamterene.

hv
rit

SIADH v/s DI :
|
w
ro
ar

SIADH DI
M

Presentation Hyponatremia Polyuria

©

S. Osmolality Hypotonia Hypertonia

S. Na+ ↓ ↑
Urine volume ↓ ↑↑
Urine osmolality Relatively ↑ Relatively ↓
Urine Na+ ↑ (>30 mEq/L) Normal
Plasma volume Euvolemic
• Acute : 3% saline
Treatment Based on type of DI
• Chronic : Fluid restriction, vaptans

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 134

----- Active space ----- ENDOCRINOLOGY REVISION - 3

Primary Hyperaldosteronism (PHA)  00:01:12

Pathophysiology :
Hyporeninemic hyperaldosteronism :
Aldosterone ↑↑ Renin ↓ 1° hyperaldosteronism.
(Adrenal gland)

Note :
Hyperreninemic aldosteronism is seen in 2° hyperaldosteronism :
↓ renal perfusion RAAS activation ↑aldosterone.

om
l.c
Causes :
ai
Acquired : gm
@

• Micronodular B/L adrenal hyperplasia (M/c).

60
23

• Adenomas (Mostly U/L) Conn’s syndrome.

ik
hv

Inherited :
rit
|

Familial hyperaldosteronism (Autosomal dominant) : Type 1 aka GRA (Glucocorticoid

w
ro

remediable aldosteronism).
ar
M
©

Presentation :
Age : 20-60 years.
Sex : M=F.

Triad of PHA :
1. Hypertension :
- Disproportionate target end organ damage.
- M/c endocrine cause for 2° hypertension.
2. Hypokalemia : Weakness, ↑ Urine K+.
3. metabolic alkalosis.

Note : PHA (Acquired/GRA).

DDx Cushing syndrome.
Hypokalemia + HTN + metabolic alkalosis
Apparent Mineralocorticoid
Excess (AME).
Liddle syndrome.

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 Endocrinology Revision - 3 135

Management : ----- Active space -----

Screening test Confirmatory test Imaging

PAC ≥ 10 ng/dL Saline infusion test : CT adrenal
PRA < 1 ng/mL/hr 2L NS over 4 hours.

PAC ≥ 10 ng/mL

• PAC : Plasma aldosterone concentration U/L adenoma

• PRA : Plasma renin activity
• AVS : Adrenal venous sampling
B/L hyperplasia >35 years <35 years :
U/L adrenalectomy

AVS :

om
B/L renal veins aldosterone : Cortisol measured

l.c
ai
gm
>4 : 1 <4 : 1
@
60

Lateralisation No lateralisation
23
ik
hv

Adrenalectomy. Medical mx :
rit
|

Aldosterone antagonists :
w
ro

Eplerenone, Finerenone, Spironolactone.

ar
M
©

Adrenal Insufficiency/Addison’s Disease 00:12:03

Primary V/S Secondary Addison’s Disease :

1° 2°
Adrenal cortical cause Pituitary insufficiency :
Etiology
Autoimmune >TB D/t abrupt steroid withdrawal (M/c)
ACTH ↑ ↓
Aldosterone ↓↓ Normal
S. K+ ↑ Normal
S. Na+ Low Low
Mineralocorticoid deficiency + -
Salt craving, Postural
+ -
hypotension
Hyperpigmentation + -
Vitiligo + -
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 136 Medicine

----- Active space ----- 1° ADDISON’S DISEASE

Causes :
Acquired :
1. Autoimmune :
- M/c worldwide.
- Autoimmune polyendocrine syndromes (APS)/Polyglandular autoimmune
syndromes (PGA).
2. TB : M/c in India.
3. Waterhouse-Friderichsen syndrome.

Inherited :
1. AAA syndrome (D/t aladin gene mutation) :
- Alacrimia.
- Achalasia cardia.

om
- Addison’s.

l.c
4A syndrome : AAA + ANS dysfunction.
ai
gm
2. X-linked adrenoleukodystrophy (D/t ↑ very long chain fatty acids).
@
60

Clinical Features :
23
ik
hv

Hormone insufficiency manifestation

rit
|
w

• Asthenia, weight loss.

ro
ar

• Hypoglycemia & hypertension : Repeated episodes.

M

Cortisol
©

• Euvolemic hyponatremia.
• Eosinophilia.

Dehydration, salt wasting, hyperkalemia,

Aldosterone
postural hypotension.
Sex steroids Dry skin.
ACTH Hyperpigmentation.

Other feature : Extra adrenal calcification (Eg : Auricular).

Note :
2° Addison’s : Clinical features a/w ACTH and aldosterone insufficiency is not seen.
Investigations :
CT adrenals : Normal/Small/Asymmetrical.

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 Endocrinology Revision - 3 137

Serological work-up : ----- Active space -----

Fasting cortisol

<3 μg/dL 3-20 μg/dL >20 μg/dL

1° Addison’s confirmed. Synacthen stimulation test : Addison’s disease

Synthetic ACTH 250 μg/dL ruled out.
IV/IM given
values measured at 1 hour
and 2 hours & highest
value is taken

>20 μg/dL : <20 µg/dL :

1° Addison’s ruled out. 1° Addison’s confirmed.

om
l.c
ADDISONIAN CRISIS
ai
gm
Emergency condition.
@
60

Clinical features : Acute abdominal pain + hypotension + shock.

23
ik

Management :
hv
rit

1. 3-4L of NS over 8-12 hours.

|
w

2. 100 mg IV hydrocortisone STAT

ro

1st day, total dose : 300 mg.

ar

3. 50 mg IV hydrocortisone 6 hours apart

M

4. Taper the dose from day 2 to day 4 Switch to oral hydrocortisone.

©

Cushing’s Syndrome 00:23:27

Pathophysiology :
Cortisol 11-bHSD-2 Cortisone (Only glucocorticoid activity).
(Glucocorticoid +
Mineralocorticoid activity)
Defect in enzyme : 11-b-hydroxysteroid dehydrogenase type 2 (11-bHSD-2)

Hypercortisolism
Can be

Inherited : Acquired :
Apparent mineralocorticoid excess (AME). • ↑ Licorice consumption.
• Cushing’s syndrome.
Medicine Revision • v4.0 • Marrow 8.0 • 2024
 138 Medicine

----- Active space ----- Causes of Hypercortisolism :

1. Endogenous :

ACTH dependant (90%) ACTH independant :

• Adrenal adenoma (M/C)
• Adrenal Ca (Toddlers)
• McCune Albright syndrome (Infants)
• Micronodular hyperplasia/PPNAD
(Primary Pigmented Nodular Adrenal
Disease) a/w Carney’s complex
• Macronodular hyperplasia

Cushing’s disease m/c : Paraneoplastic :

om
ACTH secreting pituitary Small cell Ca of lung > Carcinoid,

l.c
ai
microadenoma. Medullary thyroid Ca, Bronchial ca.
gm
@
60

2. Exogenous : ↑ steroid intake.

23
ik

Clinical Presentation :
hv
rit
|

Action Clinical features

w
ro

Catabolism In ↓ order of discriminatory value :

ar

1. Proximal myopathy.
M

• Most tissues : ↓ Amino 2. Facial plethora.

©

acid uptake. 3. Violaceous purplish striae.

Protein
• Luier : ↑ Aa uptake 4. Bruising (D/t platelet dysfunction).
5. Young onset osteoporosis/short stature.
6. Disproportionate HTN & DM
(Not d/t protein catabolism).
↑ Alanine

Carbohydrate ↑ Gluconeogenesis Diabetes mellitus

↑ hepatic glucose output

Redistribution of fat ± Buffalo hump, moon face, centripetal
Fat
minimal lipolysis obesity
1. Salt & H2O retention
Mineralocorticoid ↑ 2. Hypokalemia
3. Metabolic alkalosis
Sex steroids ↑ Acne, Hirsutism
Steroid induced psychosis, depression,
CNS -
anxiety

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 Endocrinology Revision - 3 139

Other features : ----- Active space -----

• Eosinopenia. • Menstrual irregularity
• Prone for infection. (Oligomenorrhea, Amenorrhea).
• DVT.

Management :
Diagnostic criteria for endogenous hypercortisolism :
1. Midnight Serum cortisol : >1.8 μg/dL
2. Midnight salivary cortisol : >5.5 nmol/L If 2 out of 3 + : Endogenous
3. ONDST or LDDST (Specific) : >1.8 μg/dL hypercortisolism confirmed

Work up & treatment :

Midnight serum cortisol ↑ or
Midnight salivary cortisol ↑

om
l.c
+ -

ai
gm
8am serum cortisol Cushing’s syndrome
@

ruled out.
60
23
ik

> 1.8 μg/dL Too low

hv
rit

(Loss of diurnal variation :

|

Earliest finding) Exogenous hypercortisolism.

w
ro
ar
M

Endogenous hypercortisolism
©

is suspected

Suspected Cushing syndrome Suspected pseudocushing/Obesity/

Hyperestrogenism/PCOS/on oral
Over night dexamethasone contraceptive pills
suppression test (ONDST) :
1 mg oral dexamethasone at 11 pm Low dose dexamethasone
suppression test (LDDST) :
Next day 8 am plasma cortisol 0.5 mg Q6H for 2 days

> 1.8 μg/dL

<1.8 μg/dL >1.8 μg/dL

Normal.
Endogenous hypercortisolism confirmed.

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 140 Medicine

----- Active space ----- Endogenous hypercortisolism confirmed

Then evaluate
ACTH

<10 pg/mL >10pg/mL

ACTH independant : ACTH dependant

Adrenal cause

CT adrenals 10-100 pg/mL >100 pg/mL

U/L adenoma (M/C cause) Pituitary/PNS Paraneoplastic syndrome

Rx : U/L adrenalectomy. (PNS)

om
Gd enhanced MRI brain

l.c
PET scan.
ai
gm
@

≥6 mm mass <6 mm mass/no mass

60
23
ik

Pituitary adenoma Inferior petrosal sinus

hv
rit

Rx : Trans sphenoidal sampling (IPSS).

|
w

hypophysectomy. Petrosal/Peripheral ACTH

ro
ar

ratio measured
M
©

>2 <2

+ -

Trans sphenoidal PET scan : To rule out PNS.

hypophysectomy.
Medical mx (Limited role) : Ketoconazole.
Pheochromocytoma 00:47:57

Pathophysiology :
• Neural crest cell tumor ↑ production of catecholamines & its metabolites.
• Adrenal medulla hormones :
Catecholamines Adrenaline (80%) Noradrenaline (NA) (20%) Dopamine
• metanephrine
Metabolites Normetanephrine HVA (Homovanillic acid)
• VMA (Vanillylmandelic acid)
• NA PNMT Adrenaline.
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 Endocrinology Revision - 3 141

Causes : ----- Active space -----

Adrenal (75%) : Adrenaline > NA.
Extra-adrenal (25%)

Sympathetic (20%) : Parasympathetic (5%) :

- Functional. - Mostly non-functional.
- Organ of Zuckerland - Sites : Carotid body >
(M/c site). Jugular bulb.
• AKA Paraganglioma.
• Produces only NA (PNMT is absent outside the adrenal gland).
Association :
• 40% Hereditary :
- MEN-2, VHL, NF-1.

om
- All hereditary tumors are b/l except NF-1.

l.c
ai
• 50% Malignant : gm
- Surest sign : Metastasis.
@
60

- A/w succinate dehydrogenase B mutation.

23
ik

Note : Rule of 10 is outdated.

hv
rit

Clinical Presentation :
|
w

M/c sign : Episodic hypertension.

ro
ar
M

6 Ps and 1W :
©

• Palpitations + severe episodic headache (M/c)

Triad of pheochromocytoma.
• Perspiration
• Pain (Abdominal pain d/t hypercalcemia).
• Pallor (Suggestive of malignancy).
• Panic attack (2nd m/c).
• Postural hypotension.
• Weight loss.

Investigations :
Lab investigations :
1. 24 hour urine fractionated metanephrine (98% sensitivity & specificity) :
Screening test.
2. Plasma fractionated metanephrine (100% sensitivity, But low specificity) :
Done if 24 hr urine fractionated metanephrine test is - but clinical suspicion
for pheochromocytoma is very high.

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 142 Medicine

----- Active space ----- IOC :

• Adrenal pheochromocytoma : MRI abdomen.
• Extra-adrenal pheochromocytoma : Gallium DOTATATE PET scan.

Treatment :
Surgery : Laparoscopic retroperitoneal adrenalectomy.
Pre-operative mx :

Days before surgery Drug

10 Liberal IV fluid therapy
Phenoxybenzamine (M/c)
7-10 α-blockers
Prazosin
2-3 b-blockers Atenolol
HTN crisis during surgery : Sodium nitroprusside or nicardipine.

om
l.c
Multiple Endocrine Neoplasia (MEN) 00:59:16

ai
gm
• Autosomal dominant.
@
60

• M=F.
23
ik
hv

MEN-1
rit

Etiology :
|
w
ro

• Mutation of menin gene on chromsome || q (Tumor suppressor gene).

ar

• Intron inversion (M/C mutation).

M
©

Clinical Presentation :
Major manifestation :
• Parathyroid : Primary hyperparathyroidism (100%).

1° hyperparathyroidism in MEN-1 1° hyperparathyroidism

Age <40 years >50-60 years
Sex M=F F >> M
Painful bones, Renal stones,
Symptoms Abdominal groans, Psychotic Asymptomatic
moans & fatigue overtones
Asymmetrical hyperplasia of all
Etiology Adenoma (M/c cause)
4 glands

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 Endocrinology Revision - 3 143

• Pancreas : Enteropancreatic neuroendocrine tumors (50-70%) ----- Active space -----

- M/C cause of death in MEN-1.
- M/c type : Gastrinoma.
- M/c site for MEN-1 related gastrinoma Duodenum (D1, D2).
Note : M/c site for sporadic gastrinoma Passaro triangle.
• Pituitary : Prolactinoma (Aggressive macroprolactinoma).

Minor manifestation :
• Skin : Angiofibroma (M/c), Collagenoma, Lipoma.
• Neurogenic tumor meningioma (M/c).
• Overall m/c tumor : Adrenocortical tumors (30%).
• Pheochromocytoma in MEN-1 : <1%.
• PNET (Primitive neuroectodermal tumors) : Thymic & foregut carcinoid.

MEN 2A

om
Etiology :

l.c
ai
Point mutation of RET proto-oncogene on chromosome 10q. gm
@
60

Types :
23

1. Classical MEN 2A : 2. MEN 2A with cutaneous lichen

ik
hv

- Medullary thyroid Ca (100%). amyloidosis.

rit
|

- Pheochromocytoma (50%) : 3. MEN 2A with Hirschsprung’s disease.

w
ro

Inherited, B/L. 4. FMTC (Familial medullary thyroid

ar
M

- Parathyroid hyperplasia (25%). cancer).

©

MEN 2B :
Manifestations :
Medullary thyroid Ca + Pheochromocytoma + 3 Ms ± megacolon.
3 M’s :
• Marfanoid habitus.
• Mucosal ganglioneuromas.
• Myelinated corneal nerve fibres.

MEN 4
Etiology :
CDK1B mutation (CDK : Cyclin dependant kinase).

Manifestations :
• Parathyroid involvement. • Gonadal tumors : Ovarian/testicular.
• Pituitary tumors. • Renal/Adrenal tumors.

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 144 Medicine

----- Active space ----- MEON 01:08:46

MEON : Multiple Endocrine & Other Organ Neoplasia Syndromes

Inheritance/Defect Genes Endocrine manifestation Neoplasia
Hyperparathyroidism - Parafibromin/ Hyperparathyroidism d/t Ossifying fibroma of
Jaw tumor (HPT-JT) CDC 73 parathyroid carcinoma jaw
• PPNAD/Lean cushing
Carney complex PPKAR1A • Acromegaly Atrial myxoma
• Prolactinoma (Rare)
• Renal cell Ca
VHL (Von Hippel Lindau VHL gene on
Autosomal dominant Pheochromocytoma • Cerebellar
disease) chr 3
hemangioblastoma
NF-1 (Neurofibromatosis Neurofibromin on Optic nerve sheath
Pheochromocytoma
type 1) chr 17 tumors
• Hamartomatous
Cowden’s syndrome Autoimmune

om
PTEN mutation polyps of GIT
(CWD) hypothyroidism
• Ca breast

l.c
ai
Post zygotic • Adrenal cushing
gm
McCune Albright Post zygotic GS α Polyostotic fibrous
mutation of • Acromegaly
@

syndrome subunit defect dysplasia

60

GNAS-1 gene • Prolactinoma (Rare)

23

PPNAD : Primary pigmented nodular adrenocortical disease.

ik
hv
rit

Note : Carney’s triad : Pulmonary chondroma + GIST + Paraganglionoma.

|
w
ro

PGA (Polyglandular Autoimmune Syndrome)

ar

01:13:37
M
©

AKA APS : Autoimmune polyendocrine syndromes.

APS-1 APS-11
Age of onset Childhood Adult
Gender association M=F F>M
Skin & nail changes,
candidiasis
+ -
Associated gene APECED gene mutation HLA-DR3 and DR4 association
Inheritance pattern Autosomal recessive Polygenic
Anti 21-OH antibody
Antibody
(M/c cause for addison’s disease)
-
1. Addison’s disease.
1. 1° hypoparathyroidism.
Major manifestations 2. Hashimoto’s thyroiditis >
2. Graves > Hashimoto’s thyroiditis.
Grave’s (Rare).
• Addison’s disease.
• Type 1 DM.
Minor manifestations • Type 1 DM.
• Hypogonadism.
• Hypogonadism.
APECED : Autosomal polyendocrinopathy candidiasis & ectodermal dystrophy.
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 Endocrinology Revision - 4 145

ENDOCRINOLOGY REVISION - 4 ----- Active space -----

Hypercalcemia  00:01:15

Adjusted total calcium/Normal S. Ca2+ : Measured Ca2+ + 0.8 x ( 4 - S. albumin).

• Includes albumin bound Ca2+.
• Normal range : 8.6 - 10.3 mg/dl.

Pathophysiology :
_ Parathyroid gland.
↑ S. Ca2+ (Ionised) Ca2+ sensing receptor
(CaSR) Thick ascending limb of loop of Henle.
_ Ca2+ reabsorption

om
↑ Calcum excretion

l.c
ai
gm
Stone formation
@

Causes :
60

1. PTH related : M/c.

23
ik

- 1˚ and 3˚ hyperparathyroidism (HyperPTH).

hv
rit
|

S. Po43- PTH
w
ro

Hyperparathyroidism Etiology S. Ca2+ (Normal = (Normal =

ar
M

2.5-4.5 mg/dl) 50-100 pg/mL)

©

Adenoma : Hyperplasia :
1˚ • 60 - 80y • Young
↑
(M/c PTH • F>M • F=M ↑ ↓
(500 pg/ml)
related cause) • A/w
MEN 1, 2
Long standing
↑↑↑
3˚ 2˚ hyperPTH ↑ ↑
( > 1000 pg/ml)
(Advanced CKD)
- Lithium induced 1˚ hyperparathyroidism. Note :
- Familial hypercalcemic hypocalciuria (FHH) : Lithium can also cause :
Loss of function mutation of CaSR • Nephrogenic DI.
• Chronic tubulointerstitial disease.
↑ Ca2+ reabsorption • Hypothyroidism ( D/t gland destruction).

Hypercalcemia + Hypocalciuria
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 146 Medicine

----- Active space ----- - Paraneoplastic hypercalcemia / humoral hypercalcemia of malignancy

(HHM) : _
• ↑ PTH-rp (related peptide) PTH PTH < 50pg/ml, ↑ Ca2+.
• Seen with squamous cell carcinoma (Scc).
2. Vitamin D related :
↑ Ca2+ absorption.
- Active form : 1,25 (OH)2 D3 / Calcitriol
(-) PTH
Form of vitamin D
1, 25 (0H)2 D3 25 (0H)2 D3
t 1/2 6-8 hours 2-3 weeks
Hypervitaminosis D ↑ ↑
Sarcoidosis, acromegaly, lymphomas ↑ Normal

3. Osteolytic hypercalcemia : Multiple myeloma, CA breast.

om
4. Endocrine : Pheochromocytoma, addisonian crisis, thyrotoxicosis, acromegaly.

l.c
ai
5. Drugs : Thiazides, lithium. gm
@

6. Milk alkali syndrome : ↑ Ca2+ consumption ( >4g/day)

60
23

Clinical Features :
ik
hv

• Painful bones : D/t osteolysis.

rit
|

• Renal stones.
w
ro

• Abdominal groans : In sarcoidosis & addisonian crisis.

ar
M

• Psychotic moans.
©

• Fatigue overtones (M/c).

Pseudoclubbing
• Pseudoclubbing : Normal lovibond angle.
Investigations :
X-ray :
• Subperiosteal bone resorption. Radial aspect of
• Rugger jersey spine. Middle phalynx
of Index &
• Acral osteolysis. middle fingers
• Osteitis fibrosa cystica.
Subperiosteal resorption
• Salt & pepper skull.
• Diffuse bone resorption.

ECG : Short QT interval.

Short QT interval
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 Endocrinology Revision - 4 147

Tc 99 sestamibi : ----- Active space -----

Hyperfunctioning
Hyperfunctioning parathyroid
parathyroid gland
Thyroid normalises
Hyperfunctioning thyroid
+ parathyroid

Early Scan Late Scan

Treatment :

Acute : Definitive : Surgery.

• Hydration : To prevent • Adenoma : Removal of adenoma.
nephrogenic DI. • Hyperplasia : Removal of 3½ glands.
• Bisphosphonates.
• Calcitonin.

om
Hypocalcemia  00:21:10

l.c
ai
gm
Etiopathogenesis :
@

2˚ hyper PTH :
60
23

• CKD Inhibition of lα hydroxylase, ↓ calcitriol Hypocalcemia

ik
hv

+ Parathyroid
rit

↑↑ PTH, ↓ S. Ca2+, ↑ S Po43-

|
w

Clinical Presentation :
ro
ar

• Arrhythmia : Prolonged QT interval.

M

• Pseudotumour cerebri : Seizures & papilledema (D/t ↑ ICT) or calcification.

©

• Neuromuscular irritability : Circumoral tingling, numbness, parasthesia, latent

tetany (Chvostek’s sign & Trousseau’s sign).

Investigations :
• ECG : ↑ QT interval.
• CT brain : Basal ganglia calcification.

↑ QT interval Basal ganglia calcification

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 148 Medicine

----- Active space ----- Work - up : ↓ S Ca2+

Rule out hypomagnesemia (Gitelman syndrome, PPI use) ↓ S. Po43-

Check S. Po43- & S. PTH levels

↑ PTH ↓↓↓ PTH Normal PTH

↑ S. Po43- ↑ S. Po43- ↑ S. Po43-

Secondary True • Rhabdomyolysis

hyperparathyroidism hypoparathyroidism • Tumour lysis syndrome.
Eg : CKD.
Genetic Acquired

om
l.c
Di George Autoimmune polyglandular
ai
gm
syndrome. syndrome-1 (APS-1).
@
60

Pseudo Hypoparathyroidism :
23
ik

Resistance to PTH action (↑ PTH) ↓ S. Ca2+, ↑ S. Po43- .

hv
rit

Bone mineral
|

Types Etiopathogenesis Biochemistry

w
ro

changes
ar
M

1a • Gsα defect d/t + ↓ Ca, ↑ PTH, ↑ P

©

Pseudo pseudo GNAS gene mutation.

+ Normal
hypoparathyroidism • Complete resistance.
1b No Gsα defect - -
↑ cAMP in urine
2 Partial resistance -
(If PTH is given)
Bone mineral density changes :
Knuckle Knuckle Dimple Dimple
• Short stature, round facies, mental retardation.
• Albright hereditary osteodystrophy :
Short 4th metacarpal/metatarsal.

Treatment :
Acute : 10% Calcium gluconate 10 ml over 10 mins.
Chronic :Long term Ca2+ supplementation.
↑ Ca2+ supplementation Milk alkali syndrome. Knuckle knuckle
dimple dimple sign

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 Endocrinology Revision - 4 149

Thyroid Disorders  00:32:08 ----- Active space -----

Development :
Thyroid Parafollicular C-cells
• 3-4 weeks (1st endocrine organ) Ultimobranchial body
Derivative
• Endodermal origin (Neural crest)
Synthesis T3 < T4 ( 10x times) Calcitonin

THYROID HORMONES :
Steps of Synthesis :
1. Sodium iodine symport (Basolateral membrane) : Used in Tc99 / I133 scintigraphy.
2. Iodide - chloride antiport (Pendrin) : Pendred syndrome.
3. Organification : I- I2 ,
Mediated by thyroid peroxide (TPO)/dual oxidase (DUOX).

om
l.c
4. Iodination of thyroid residues MIT, DIT (Enzyme independent).
ai
5. Coupling : MIT + DIT T3 , DIT + DIT T4. gm
@

6. Reuptake into epithelial cells.

60
23

7. Proleolysis and release of hormone.

ik
hv

Peripheral Conversion :
rit
|

• T4 Deiodinase - 2 T3
w
ro

• T4 Deiodinase - 3 rT3 (Reverse T3)

ar
M
©

Deiodinase - 2 inhibitors :
• PTU. • Amiodarone.
• Steroids. • Propranolol.
Properties :
• Thyroid hormones binds to :
Thyroid binding globulin (60 - 70 %), albumin (20%), transthyretin (10%).
Sick Euthyroid Syndrome /Low T3 Syndrome :
• Seen in sick patients, systemic illness fasting.
• T4 rT3 d/t impaired conversion of T4 T3.
Early stages Advanced stages
T3 ↓↓ ↓
T4 Normal / ↑ ↓
rT3 ↑↑ ↑
TSH Normal ↓
Medicine Revision • v4.0 • Marrow 8.0 • 2024
 150 Medicine

----- Active space ----- Investigations :

Hyperthyroxinemia work-up :
↑↑ TSH Normal TSH ↓ TSH
(> 5mIU/L) (0.5-5 mIU/L) (< 0.5 mIU/L)
1. Symptomatic :
1˚ Hypothyroidism Hypopituitarism
fT3 & fT4 Pituitary cause.
(Autoimmune) : (Inappropriately
↓↓ 2. Asymptomatic : Last stage of
Hashimoto’s thyroiditis. normal)
sick euthyroid.
fT3 & fT4
Subclinical hypothyroidism - -
Normal
• Toxic : TSH secreting
Thyrotoxicosis :
pituitary adenoma.
1. D/t overworking gland :
• Resistance to thyroid
fT3 & fT4 Hyperthyroidism.

om
hormone (RTH) : -
↑↑ 2. D/t ↑ stored hormone release :

l.c
- D/t unresponsive
ai
Thyroiditis (Subacute).
gm
receptors.
3. Drug induced : Amiodarone.
@

- Euthyroid presentation.
60
23

Euthyroid Hyperthyroxinemia :
ik
hv

• Asymptomatic.
rit

• D/t ↑ TBG : Pregnancy, OCP, chronic active hepatitis, tamoxifen.

|
w

• Investigations :
ro
ar

- fT3 & fT4 : Normal. - Total T3, T4 : ↑

M
©

Functions of Thyroid Hormone :

Functions
CVS ↑ CO, ↑ BP (In hypothyroidism : ↑Peripheral resistance ↑BP)
Bone ↑↑ Secretion Osteoporosis
CNS Myelination of CNS.
RBCs Stimulates erythropoiesis.
↑ Proteolysis Osteopenia, hypercalcemia,
Protein
stones formation,muscle wasting.
Carbohydrate ↑ Gluconeogenesis & ↑uptake of glucose.
Cholesterol Cholesterol clearance ( ↓T3 hypercholesterolemia)
• ↑ Basal metabolic rate.
• Thermiogenesis by uncouplers.
Others • ↑ O2 consumption except brain & gonads.
• Beta carotene Vit A.
• ↑ Sensitivity to catecholamines (Indirect effect)
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Hypothyroidism  00:52:31 ----- Active space -----

Types :
1. 1˚ : M/C.
2. 2˚: Acquired hypopituitarism.
3. Congenital : Seen in pediatric population.
4. Consumptive : Due to hemangiomas.

PRIMARY HYPOTHYROIDISM :
Causes :
1. Autoimmune (M/c) : Hashimoto’s, APS-1 < APS-2.
- Hashimoto thyroiditis.
• HLA DR3/DR4.
• Pre-malignant Marginal zone lymphoma > Papillary thyroid CA.
(MALToma)

om
• Thyroid auto antibodies (ab) : Thyroid peroxidase (TPO) ab (90-100%),

l.c
ai
thyroglobulin-ab (80-90%) & TSH receptor ab (20%).
gm
2. Surgical removal. 4. IFN - α
@
60

3. Iodine deficiency. 5. Amiodarone.

23
ik
hv

Histology :
rit

• Destruction of thyroid • Follicular atrophy.

|
w
ro

gland architecture. • Germinal centre formation.

ar

• Oxyphil metaplasia.
M

• Lymphocytic infiltration.
©

Clinical Presentation :
• Females, 45-65 yrs.
Accumulation of matrix GAGS
↓Metabolic processes Others
(Traps water in interstitum)
• Fatigue • ↓Attention/Concentration
• Weight gain • Puffiness • Hair loss
• Constipation • Macroglossia • Menorrhagia
• Dryness of mouth • Non-pitting edema • Infertility
• Bradycardia • Periorbital edema • Oligomenorrhea
• Cold intolerance • Myxedema • Delayed DTR
• Hoarseness of voice • Dry Skin
O/E : Thyroid swelling.
- Heterogenous, irregular, firm.
- Nodules absent.

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 152 Medicine

----- Active space ----- Investigation :

• fT3, fT4 : ↓↓ / N, TSH ↑↑, Antibodies + Hashimoto’s thyroiditis.

Treatment :
• Levothyroxine 1.6-1.8 μg/kg/day.
Note :
False +ve hypothyroidism : Addison’s disease.
Rx :
1. Cortisol management. 2. Thyroid correction.

Myxedema Coma :
Cause : Infection + untreated hypothyroidism.
Presentation : Impaired consciousness + seizures.
O/E : Profound bradycardia, hypothermia, hypoventilation, hypoglycemia,
hyponatremia.

om
l.c
Investigations : ECHO Pericardial effusion, ECG Low voltage complexes.
ai
gm
Rx : IV Levothyroxine (Orphan drug), IV steriods.
@
60
23

Hyperthyroidism 
ik

01:02:42
hv
rit

Types : Diffuse enlargement : Graves disease (Autoimmune).

|
w

Hyperthyroidism 1˚
ro

Nodular enlargement : Toxic nodule, toxic MNG.

ar
M

2˚ TSH adenoma (Rare).

©

Graves Disease :
Clinical Presentation :
• Age : 20-40yrs.
• Sex : F > M.
• Associations : H/o Smoking, HAART ( Highly active antiretroviral therapy).
• Apathetic thyrotoxicosis (elderly) : Asymptomatic, fatigue.

Pathogenesis Manifestation
• Restless/anxiety/tremor.
• Arrhythmia : Atrial fibrillation.
• Hypokalemic periodic paralysis.
↑ fT3 & fT4
• Proximal myopathy.
• Diarrhoea.
• ↓ Bone mineral density fracture.

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Pathogenesis Manifestation ----- Active space -----

TSH receptor antibodies

Ophthalmopathy
Stimulates fibroblasts

GAGs activation

Dermopathy Acropachy

om
Antibodies : TSH receptor ab (80%) > TPO ab (50-80%) > Thyroglobulin ab (50-70%).

l.c
ai
Investigation : Thyroid scintigraphy ( I123 or Tc99 ) : Diffuse ↑ uptake.
gm
@

Treatment :
60
23

• 1st line : Thionamide (Carbimazole) 5mg TDS + Propranalol 40mg Q6H.

ik
hv

If C/I (Pregnancy, children)

• Relapse (50%) : Radioiodine ablation Surgery.
rit
|
w

Subacute/de Quervains/Viral/Granulomatous thyroiditis :

ro
ar

C/F : Fever, sore throat, painful thyroid.

M
©

Investigations :
• ESR ↑.
• Scintigraphy : Low uptake.
• TSH, T4 :
- Initial (Thyrotoxicosis) : TSH ↓, T4 ↑.
- Later (Hypothyroid) : TSH ↑, T4 ↓.
Rx : Aspirin (DOC), NSAIDS, Steroids.
Postpartum/Painless/Silent Thyroiditis :
Autoimmune illness (+) : M/c a/w type I DM.
Investigations : ESR : Normal, Anti TPO ab (+).
Rx : Supportive, no role of steroids.
Chronic/Riedel’s Thyroiditis :
• IgG4 related disease.
• TFT : Normal.
• Dense, hard thyroid mass.
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 154 Medicine

----- Active space ----- Diabetes Mellitus  01:13:00

CLASSIFICATION :
Types Characteristics
• Autoimmune pancreatic destruction (Tcell + B cell mediated).
1 • Fasting C peptide / C-peptide in response to glucagon : ↓↓
• Rx : Insulin.
• Insulin resistance, ↑ lipolysis.
• Microvascular complications : Ophthalmopathy neuropathy, nephropathy.
2 - Dependant on blood sugar control in initial 5 years.
• Macrovascular : Cardiac complications (M/C).
- Independent of blood sugar control.
• Ketosis prone diabetes.

om
1.5 KPD • Type 2 Dm, manifesting as type I DM.

l.c
ai
• Latent autoimmune diabeles in adult.gm
@

1.5 LADA • Type 1 DM manifesting as type 2 DM.

60

• Antibodies +
23
ik

• Brain diabetes/double diabetes/Alzheimer’s disease :

hv

3
rit

Insulin resistance in brain.

|
w

• Pancreatic diabetes.
ro
ar

3c • Cause : Tropical chronic calcific pancreatitis, hemochromatosis,

M
©

IgG4 related disease, cystic fibrosis.

3d Drug induced diabetes : L-asparginase, growth hormone, tacrolimus.
• Elderly
4 • Minimal symptoms & complications.
• ↑ T - regulatory cells.
• Maturity onset diabetes of the young.
• MODY - 3 (M/c) d/t HNF-I α defect.
MODY
• No symptoms, no complication, no resistance, good prognosis.
• Slightly ↑ blood sugar.

MANAGEMENT OF TYPE 2 DM :
Evaluation :
1. Continuous blood sugar monitoring. 4. Ophthalmic evaluation.
2. HbA1c 5. Nerve conduction study.
3. Urine routine. 6. Treadmill test + Angiography.
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Insulin Therapy : ----- Active space -----

Indications : Types :
• HbA1c ≥ 9.5 at presentation. Duration of action Names
• Microvascular complication +. Ultra short Lispro
• H/o macrovascular complication.
Short Regular
• Diabetic ketoacidosis.
Intermediate NPH
• T1 DM / LADA.
Long Glargine
Target HbAIc : 7%. Ultra long Degludec
Regimen :
• Total insulin to be given : 40 units.
• 24U of regulin insulin (8U x 3 times/day) + 16 U glargine (daily)/ degludec
(alternate days).

om
Note : Artificial pancreas Best Rx.

l.c
ai
OHA : gm
Metformin : 500 mg BD.
@
60

• MOA : ↑ AMP kinase ↑ glucose uptake & ↓ gluconeogenesis Acts against

23
ik

insulin resistance.
hv
rit

• C/I : GFR < 240 ml/min Risk of lactic acidosis.

|

• Advantages :
w
ro
ar

- Good potency : ↓HbAIc by 1.5%.

M

- No risk of hypoglycemia.
©

- Weight loss.
- No effect on CVS.
• Add-on to metformin : For comorbidity control, given in
- Atherosclerotic Vascular disease (CAD, LVH) : GLP-1 analogue /SGLT2
inhibitors.
- Heart failure with reduced ejection fraction : SGLT2 inhibitors.
- CKD : SGLT2 inhibitors.

SGLT2 inhibitor :
• Dapagliflozin 10mg (Or) Empagliflozin 25 mg.
• Advantages :
- Promotes diuresis, natriuresis. - Inhibit RAAS.
- No tachycardia. - Prevents proteinuria.
• Disadvantages : ↑ UTI risk, ↑ ketosis.

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 156 Medicine

----- Active space ----- GLP-1 Analogue > DPP4 Inhibitors :

Actions :
GLP-1 analogue DPP4 (-)
Drugs Liraglutide (S/c)
Gliptin
Semaglutide (Oral)
CVS Cardiac neutral
Weight Loss Neutral
Glucagon ↓
Potency 1.25% ↓ 0.75% ↓
Gastric emptying Delay No action

Standard prescription :

om
• First line : Metformin 500 BD (Max dose : 1g TDS).

l.c
• Add on : SGLT2 inhibitor (Dapagliflozin) 5mg OD + Liraglutide 0.6 - 1.8 mg S/c.
ai
gm
@

Sulfonylureas :
60

• High CVS mortality risk.

23
ik

• Gliclazide can be tried.

hv
rit
|
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ro
ar
M
©

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 157

CNS REVISION - 1 ----- Active space -----

Types of headache :

Primary (90-95%) Secondary (5-10%)

• Benign; recurrent. • Infections (Mainly).
• No structural cause. • Brain tumors.
• Causes :
1. Tension type headache.
2. Migraine.
3. Trigeminal autonomic cephalalgia (Cluster headache).
4. Trigeminal neuralgia.

om
Note : Intracranial pain insensitive structures Choroid plexus and ependyma.

l.c
ai
gm
Dangerous Headache 00:03:26
@
60

leading
1. Age of onset >55 yrs : Could be d/t Giant cell arteritis (GCA) to Blindness.
23
ik

2. ↑sing severity over weeks.

hv
rit

3. Early morning headache (Disturbing sleep) : A/w vomiting f/b relief of D/t ↑ICT.
|
w

headache.
ro
ar

4. Headache a/w blurring of vision.

M

5. Pain ↑ on bending, lifting, or coughing : D/t meningeal irritation or ↑ICT.

©

All these patients must be examined for papilledema (↑ICT).

Approach to ↑ICT Headaches :

1st Headache

MRI + MRA/MRV (Imaging of choice)

MRI findings + MRI findings -
Space occupying lesions (M/C) MR Venogram Normal MRV Benign intracranial
• Neurocysticercosis hypertension
• Tuberculoma Findings +
• Brain tumors Cerebral venous thrombosis (2nd M/C)
• Lesions compressing the stalk : • Inherited : Factor V Leiden mutation
1. Tumors • Acquired :
2. Infiltrative lesions : - Post-partum
- Sarcoidosis - APLA.
- Langerhan’s cell histiocytosis (LCH)
- Hemochromatosis
- Lymphocytic hypophysitis (IgG4 ; Post-partum).

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 158 Medicine

Benign Intracranial Hypertension :

----- Active space ----- • Middle aged obese females.
• Slowly increasing ICT (Over 3-6 months).
• CN VI palsy may be seen (False localizing sign) All other CNS findings normal.
• High CSF opening pressure.
• Rx : Repeated guarded LP ; Topiramate/Acetazolamide.

Tension Type Headache (TTH) 00:12:21

M/C 1˚ headache.
Patient profile :
• F >>> M : 30-50 yrs.
• Headache : Band of tightness/fullness.
• A/w depression in 1/3rd cases Hence Most effective in prevention :
TCAs (Amytriptiline).
Negative history :

om
l.c
• No ↑ICT signs.
ai
gm
• Does not affect activities of daily living.
@

• No vomiting, photophobia, phonophobia.

60
23
ik

Migraine 00:14:09
hv
rit

2nd M/C 1˚ headache (Intracerebral vasoconstriction f/b Vasodilatation).

|
w
ro

Patient profile :
ar

• Females >> Males : Starts at teenage Increases in intensity with age.

M
©

• Extreme periodic nature. • Trigger : Sleep deprivation.

Types :
1. Classical (20%) : With visual aura. 2. Common (80%) : Not a/w aura.
Natural history :
1-2 days before episode : Duration : 4-72 hrs Post-headache phase (1-2 days) :
Low mood & irritability Episode : Lethargy

a. Aura : b. Headache :
• 15 mins - 1 hr before • Throbbing/pounding/pulsatile :
headache. Frontotemporal/temporal.
• Bright, zig-zag lines • U/L B/L, as the disease progresses.
in peripheral vision • A/w photophobia & phonophobia :
(Fortification spectra). Sits in a quiet, dark room.
• Vomiting +/-.
Note : Migraine must be ruled out before diagnosing sinus headache.

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 CNS Revision - 1 159

Pathology :
Initial intracerebral vasoconstriction Vasodilatation. ----- Active space -----

Mx : Prevention
Prophylaxis : Treatment : Vasoconstrictors
• Mandatory if attacks are • Mild to moderate : NSAIDs.
recurrent. • Moderate to severe :
• Class I drugs (First line agents) : 5-HT1b/1d agonists (Risatriptan, Eletriptan)
Propranolol, valproate, Use with caution if IHD+/elderly.
topiramate. • Severe to very severe : 6 mg s/c Sumatriptan
(Intranasal can also be used).

Trigeminal Autonomic Cephalalgia (TAC) 00:21:00

Types :
1. Cluster headache.

om
2. Paroxysmal hemicrania (PHC).

l.c
ai
3. SUNCT (Short lasting Unilateral Neuralgic headache with Conjunctival injection &
gm
Tearing).
@
60

4. Hemicrania continua (HC).

23
ik

General clinical features :

hv

Conjunctival congestion.
rit

• Unilateral, very severe.

|

Eyelid edema.
w

• Stabbing or boring. + Ipsilateral ANS symptoms

ro

Nasal congestion.
ar

• Short lasting/periodic.
M

Rhinorrhea, lacrimation.
©

CLUSTER HEADACHE
Features :
• Young males with periodic headaches.
• 1-8 attacks/day (Each attack 15 mins - 3 hrs).
• Alcohol is a trigger.
• Restless d/t pain.
• Headache : U/L, severe, stabbing/boring type in the peri-orbital region.
Nocturnal headache + .
• Migrainous features +/-.
Treatment :
1. 100% O2 : 12-15 mL/min for 15-20 minutes (Best).
2. 6 mg s/c Sumatriptan OD.
Prophylaxis :
1. Short term : Steroids (Or verapamil).
2. Long term : Verapamil.

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 160 Medicine

OTHER TAC
----- Active space -----
Paroxysmal hemicrania SUNCT Hemicrania continua
• Female = Male • Male > Female • Female > Male
• Less severe attacks • Cutaneous trigger • Elderly
• Less periodicity • Extremely short lasting • U/L continuous
• Nocturnal headache - • No refractory period headache
• Alcohol is not a trigger • Prevention : Lamotrigine • ANS symptoms +
• 1-20 attacks/day • Responds to
(2-30 min) Indomethacin
• Responds to Indomethacin

Trigeminal Neuralgia 00:28:55

Clinical features :

om
• Middle aged to elderly. • No sensory signs.

l.c
• Episodic neuralgic pain along • Pain follows a cutaneous trigger
ai
gm
CN V2 and V3. (Refractory period +).
@

• Tic douloureux : Characteristic wincing

60
23

with pain.
ik
hv

• Etiology according to distribution :

rit

- U/L Compression of superior cerebellar artery (M/C).

|
w

- B/L Demyelination (E.g. : MS).

ro
ar

Treatment :
M
©

• Medical : Carbamazepine (CBZ) > Lamotrigine (Check for H LA-B1502 before

administering CBZ).
• If not responsive Decompressive surgery.

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 CNS Revision - 2 161

CNS REVISION - 2 ----- Active space -----

Lower Motor Neuron Lesions  00:00:30

LMN Component Associated conditions/Affected by

• Degenerative motor neuron disease : Amyotrophic lateral sclerosis
Anterior horn cell
(Anterior horn cell + Corticospinal tract = UMN + LMN disease)
( α and γ motor neurons
• Pure LMN : Spinal muscular atrophy (SMA)
in spinal cord gray matter)
• Central canal syndrome Syringomyelia
• Sjogren’s syndrome : Asymmetrical truncal + U/L severe sensory ataxia
Dorsal root ganglion • Paraneoplastic syndrome Anti - Hu antibody +ve
• Cisplatin, Taxanes.
• Disc compression (i.e., IVDP)

om
Spinal nerve root/Radicle
• B/L polyradiculoneuropathy (Eg : Guillain - Barré Syndrome)

l.c
ai
Plexus Plexopathies : D/t tumors
gm
• Mononeuropathy : Carpal tunnel syndrome ( AL amyloidosis, Demyelinating)
@
60

• Mononeuritis multiplex : Leprosy > Polyarteritis nodosa; Cryoglobulinemia

23

• Polyneuropathy :
ik
hv

a. Acquired :
Nerve
rit

- Small fibre neuropathy (Spinothalamic tracts) : Diabetes

|

- Large fibre neuropathy (Dorsal column) : B12/Vit. E/copper

w
ro

deficiencies
ar

b. Inherited : Charcot - Marie - Tooth disease

M
©

• Myasthenia gravis
Neuromuscular junction
• Lambert - Eaton myasthenic syndrome (LEMS)
• Intermittent weakness : Channelopathies; mitochondrial myopathies
• Persistent weakness :
Muscle c. Inherited : Dystrophies
d. Acquired : P olymyositis/dermatomyositis, drugs/toxins,
endocrine causes (Thyrotoxicosis, cushings)

Pure motor Pure sensory Sensory > Motor

Pure Motor Presentation 00:20:10

Muscle - Polymyositis/Dermatomyositis :
• B/L, lower limb predominant proximal muscle weakness : Persistent.
• No ANS/Sensory/Cerebellar symptoms (Pure motor).
• CNS IX, X LMN involvement.
• Diagnosis Muscle biopsy.

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 162 Medicine

----- Active space ----- Anterior Horn Cell : Neuromuscular Junction :

• Degenerative UMN + LMN • Fatigability.
involvement. • Diurnal variation.
• Asymmetrical wasting of muscles.
• Fasciculations + .
• Deep tendon reflexes +++.
Sensory > Motor Presentation : Asymmetrical  00:28:44

RADICULOPATHIES & PLEXOPATHIES

Symptoms of radiculopathies :
• Root pain : Brief, electric shock - like sensation, worsening with cough.
• Motor weakness : Along the distribution of the root (Myotomal distribution).
• Loss of reflexes : Along the distribution of the root.
Radiculopathy Vs Plexopathy :

om
l.c
Radiculopathy Plexopathy

ai
Presentation gm
Asymmetrical sensory/sensori-motor involvement
@

M/C Etiology Compression d/t IVDP (Unilateral) Compression d/t tumor

60
23

Pain Short, electric shock like Dull aching, deep, long standing
ik
hv

Distribution Dermatomal/Myotomal Proximal + Distal weakness (Complete limb)

rit
|

Sensory/Motor Sensory > Motor Sensory + Motor (Complete limb)

w
ro

Paraspinal NCS Abnormal Normal

ar
M

NCS : Nerve conduction studies

©

Sensory > Motor Presentation : Symmetrical  00:37:16

NEUROPATHIES
Axonal Vs demyelinating :
Axonal Demyelinating
Cause DM GBS (B/L polyradiculoneuropathy)
Most commonly Chronic Acute
Chronicity • AIP
Exceptions • Hereditary coproporphyria Acute CIDP Chronic.
• Variegate porphyria
Sensory/Motor Sensory >> Motor Sensory + Motor
Evolution Distal Proximal Distal + Proximal together
Weakness Nil Prominent
Reflexes Only ankle jerk lost Reflexes lost
NCS Amplitude maximally affected Conduction velocity maximally affected
AIP : Acute intermittent porphyria ; CIDP : Chronic inflammatory demyelinating polyneuropathy.
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 CNS Revision - 2 163

Large fibre Vs Small fibre : ----- Active space -----

Large fibre neuropathy Small fibre neuropathy

• Tingling
Positive symptoms • Cotton - wool/Sensations Burning pain
• Paraesthesia/Dysesthesia
L/o pain/temperature/crude touch/pressure :
• Sensory ataxia • Non-healing ulcers
Negative symptoms
• Numbness • Charcot joints
• Burns
• Postural HTN Seen in :
• Tachy/Bradycardia • DM
Associated ANS
Not seen • Nocturnal diarrhea • Amyloid
Symptoms
• Gustatory sweating • Porphyrias
• Erectile dysfunction
A α fibres A δ + C fibres
Nerve fibres
Proprioception + Motor + Reflexes Pain + Temperature + ANS

om
l.c
• Chronic, axonal ( Distal Proximal)

ai
Course/Evolution Acute, demyelinating • Sensory >>> Motor
gm
• Stocking and glove pattern
@
60

• GBS
23

• B12/E/Copper deficiency • Acquired : DM > Leprosy> Amyloid >

ik
hv

• Pyridoxime toxicity Vasculitis > Uremia, drugs, HIV.

rit

Causes • Taxanes • Inherited : Fabry’s and Tangier’s disease.

|

• Friedrich’s Ataxia
w
ro

Combined small + Large fibre neuropathy : Vincristine and Carcinomatosis.

ar
M
©

Guillain-Barré Syndrome  00:53:29

M > F (Mean age : 40).

Types :
1. Acute inflammatory demyelinating polyradiculopathy (AIDP) : M/c
2. Acute motor axonal neuropathy (AMAN) : Anti - GD1a
Poor prognosis
3. Acute motor sensory axonal neuropathy (AMSAN)
4. Miller Fischer Syndrome (MFS) :
- Triad of MFS Ophthalmoplegia + - Anti GQ1b.
Areflexia + Ataxia. - Demyelinating disease.
AIDP :
Pathophysiology :
• Acute demyelinating neuropathy : < 4 week duration.
• Inflammatory autoimmune condition Triggered by infection (M/c : C.jejuni).
• Anti GM1 antibody +
• Fibres involved Aα (Large fibres) and B (Preganglionic ANS fibres).

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 164 Medicine

----- Active space ----- Clinical features :

• Ascending polyradiculoneuropathy LL UL Brainstem ( B/L LMN CN III/
CN VII palsy).
• Initial phase (1 - 2 d)
Rubbery legs + Tingling/paraesthesias/cotton-wool sensations.
( ± Transient bladder dysfunction)

Rapidly progressive proximal + distal lower limb weakness

B/L areflexic flaccid paraparesis.

• ANS Symptoms (Tachy/bradycardia, hypo/hypertension) may also be seen.
• Sensory symptoms/signs : Mild.

Investigations : Treatment :

om
• NCS Abnormal . • IVIG : 0.4g/kg x 5 days (Best).

l.c
ai
• CSF ↑Protein+Albuminocytological • Plasma exchange therapy (PLEX).
gm
@

dissociation.
60

Note : CIDP
23
ik

1. Relapsing neuropathy > 8 wks. 3. Preceding event in only 30 % cases.

hv
rit

2. Less precise onset. 4. A/w HIV/Myeloma/POEMS syndrome.

|
w
ro
ar

C/F :
M

• Motor > Sensory presentations. • Prominent sensory symptoms & signs.

©

• Proximal + distal lower limb • ANS symtoms -

predominant weakness . • Cranial nerve involvement -

Rx : Steroids, PLEX.

LMN Lesions : Cheat Sheet 01:03:49

C/F Most likely diagnosis

Pure motor Polymyositis/Dermatomyositis
Acute motor Hypokalemic periodic paralysis
Pure sensory Ganglionopathy (Asymmetrical truncal/U/L ataxia)
Asymmetric sensory + motor Brachial plexopathy Vs. Radiculopathy
Chronic neuropathy DM/Leprosy/Uremia/Vasculitis
Acute neuropathy GBS

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 CNS Revision - 3 165

CNS REVISION - 3 ----- Active space -----

Myasthenia Gravis 00:00:15

Clinical Profile :
• 20-40 years. • Autoimmune.
• A/w : Type 1 DM, Addison’s disease, • Females > Males (Males have more
vitiligo, pernicious anemia. severe phenotype).

Cardinal Features and Progression :

Ocular myasthenia (15-20%)
Pharyngeal Generalised
1. Fatigability Proximal

om
muscle myasthenia

l.c
2. Diurnal variation (80-85%) muscles of LL
involvement (80-85%)
ai
gm
3. Ophthalmoplegia + Ptosis
@
60

Good prognosis Pre-synaptic

23

terminal
ik

V/Q Ca2+
hv

Pathogenesis : channels
rit

+++
ACh receptors
|

• Involves the post-synaptic junction of the NMJ.

w

(Post-synaptic)
ro

• Anti-ACh-Receptor antibodies block action of ACh. Antibody ACh

ar

-
to ACh-R Post-synaptic
M

Antibodies in MG
©

terminal
Pathophysiology at NMJ
Anti-ACh-Receptor (80%) ACh-R -ve (20%)
Alw :
• Thymic hyperplasia (70%).
• Thymoma (10%). Anti-Musk Ab (50%) Double negative
• Females w/o thymus involvement.
• Absent in ocular myasthenia. Anti-LRP-4 +ve
• Tongue fasciculations.
• Unresponsive to pyridostigmine.
Clinical Features :
1. Ocular symptoms :
- First symptom in 2/3rds of cases.
- Asymmetric ptosis with B/L pupil sparing diplopia.
- M/C muscle Medial rectus.
- Differential : Chronic progressive external ophthalmoplegia (CPEO)
B/L symmetrical progressive ophthalmoplegia.

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 166 Medicine

----- Active space ----- 2. Limb symptoms : First symptom in 10% of cases.
3. Pharyngeal muscle involvement :
- First symptom in the remainder of the cases.
- Nasal twang.
- Dysarthria/dysphonia.
- Dysphagia.

Evaluation :
1. Ice-pack test.
2. Edrophonium test. Improvement of symptoms
3. Neostigmine test.
4. Repetitive Nerve Stimulation Test (RNST) :
- Step 1 : Baseline compound muscle action potential (CMAP) Normal.
- Step 2 : Low frequency (3Hz) repetitive stimulation Decremental response.

om
- Step 3 : High frequency repetitive stimulation Incremental response

l.c
(Back to normal).
ai
gm
5. Single nerve fibre electromyography : Most sensitive test.
@
60

6. ACh-R antibody : Most specific test.

23
ik

Lambert-Eaton Myasthenic Syndrome (LEMS) Vs Myasthenia Gravis :

hv
rit

• Paraneoplastic (A/w small cell carcinoma of lung) : Ab against V/Q Ca2+ channels.
|
w

• ANS Symptoms : +++

ro
ar

• Proximal lower limb weakness +++.

M

• Diplopia + Ptosis (Mild to absent).

©

RNST findings : Rx : 3,4-Diaminopyridine.

• Baseline CMAP ↓↓.
• Low frequency : Variable response.
• High frequency : ↑↑ incremental response (Supranormal).

Treatment of Myasthenia Gravis :

• Initial Rx : Pyridostigmine 30-60mg/QID.
• Myasthenic crisis : I/V steroids + IVIG.
• Relapse prevention : Add on steroids and azathioprine.

Motor Neuron Disease 00:11:40

Types :
1. Pure UMN : Primary lateral sclerosis.
2. LMN + UMN : Amyotrophic lateral sclerosis (ALS).
3. Pure LMN : Spinal muscular atrophy.
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AMYOTROPHIC LATERAL SCLEROSIS (ALS) ----- Active space -----

Pathophysiology :
• Age : >60 yrs (Uncommon <40 yrs). • Degenerative disease.
• 90% sporadic, 10% Cu-Zn superoxide dismutase.

Structures affected :
• Anterior horn cells. • Corticobulbar fibres
• Cranial nerve nuclei. (Upto cranial nerve nuclei).
• Corticospinal fibres (Upto AHC).

Clinical Features :
• Asymmetric U/L involvement, later progresses L/L.
Wasting & atrophy Fasciculations & cramps Exaggerated DTRs.
• Distal > Proximal involvement (Both seen).
• Weakness; Loss of dexterity (Last symptom).

om
Functions preserved :

l.c
ai
Higher mental functions ; Sensory system ; ANS ; Cerebellar functions.
gm
@
60

BULBAR VS. PSEUDOBULBAR PALSY

23

Either bulbar/pseudobulbar palsy is seen in motor neuron disease.

ik
hv
rit

Bulbar palsy (40%) Pseudobulbar palsy (25%)

|
w

UMN involvement (Corticobulbar fibres) :

ro

LMN involvement of CN nuclei in

ar

• Gag reflex +++; Jaw jerk +++.

M

brainstem (CN IX, X, XI, XII) :

©

• Dysphonia
• Nasal twang
• Small & spastic tongue
• Nasal regurgitation/aspiration
• Spastic dysarthria
• Flaccid tongue
(Pseudobulbar dysarthria)
• Flaccid dysarthria
• Emotional incontinence
(Bulbar dysarthria)
(Inappropriate, unregulated emotions)

Spinal Cord 00:18:40

Clinical Anatomy :
• 45cm long Extends up to L1-L2.
• 31 segments (8 cervical + 12 thoracic + 5 lumbar + 5 sacral + 1 coccyx).

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 168 Medicine

----- Active space ----- Conus & Epiconus : Localisation of spinal cord segments :
Terminal portion of spinal cord.
Spinal segment Vertebral level
L2
L3 Lower cervical +1
L4 Upper thoracic (T1-T6) +2
L5
S1 Involved in T7-T9 +3
Epiconus
S2 cauda equina T10 L1-L2
S3 syndrome
Involved in conus T11 L3-L4
Conus S4
medullaris T12 L5
S5 syndrome
C1
Filum terminale
(Pia mater)

om
Note : Arrangement of fibres in the spinal cord medial to lateral.

l.c
• All tracts : Cervical Thoracic Lumbar Sacral.
ai
gm
• Posterior column alone : Sacral Lumbar Thoracic Cervical.
@
60

COMPRESSIVE MYELOPATHY
23
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Stages of extramedullary compression :

hv
rit

Stage I : Root compression Radiculopathy-like features.

|
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Stage II : Hemisection of the cord Brown-Sequard syndrome

ro
ar
M
©

I/L pyramidal tract I/L posterior column C/L spinothalamic tract

Stage III : Complete involvement.
Intramedullary Extramedullary
Intradural : Neurofibromatosis; Meningioma
• Ependymoma
Causes Extradural (M/C) :Vertebral causes (Fracture,
• Syringomyelia
mets, TB), rarely aneurysm
Root pain
Pain Funicular, dull aching
(Tightness/band like in posterior compression)
Dissociated sensory loss : M/C : Posterior column involved
Sensory
• Spinothalamic tract +
symptoms
• Posterior column spared (Radiculopathy Brown-Sequard Complete)
Bowel & bladder Involved Spared
Minimal symptoms
Motor Predominant (LL > UL)
(Sacral sparing)
LMN features
+ -
(AHC involvement)

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 CNS Revision - 3 169

Note : Glove and stocking neuropathy. ----- Active space -----

U/L sensory involvement + L/L motor involvement (In extramedullary pathologies).

Cauda equina vs Conus medullaris :

Conus medullaris Cauda equina
Roots involved S3-C1 L2-C1
Extent/symmetry B/L symmetrical involvement Asymmetrical involvement (Root pain)
Motor symptoms - Variable (Depends on roots involved)
Reflexes Anal/bulbocavernosus reflexes lost Variable loss of reflexes
Bladder LMN bladder No bladder involvement
Anaesthesia Saddle anaesthesia Variable patterns of anaesthesia

NON COMPRESSIVE MYELOPATHY

Causes : VITAMIN

om
Vascular : Anterior spinal A. infarction. Metabolic : B12/Vit E/Cu2+ deficiencies.

l.c
ai
Inherited : Friedreich’s ataxia. Infectious : TB, HIV.
gm
@

Toxins : Arsenic. Neoplasia.

60

Autoimmune : Sarcoidosis.
23
ik
hv

Acute Transverse Myelitis (ATM) :

rit
|

Bilateral lower limb areflexic atonic paraparesis (Similar to GBS).

w
ro

Rx : Steroids.
ar
M

ATM vs GBS :
©

1. Infectious trigger : Clear history (Compared to GBS).

2. Clear level of symptoms :
- Band like sensation perceived.
- Hyperaesthesia at the level; UMN findings below the level.
(Power/Sensations - ; Reflexes ++).
3. Bowel/bladder symptoms +++ (Not seen in GBS).

Vitamin B12/E/copper deficiency :

Posterolateral cord + Nerve ± Cerebrum (Rare) involvement.
Clinical features & progression :
Posterior column Lateral spinothalamic tract Corticospinal tract

Reflexes lost later in the disease Large fibre neuropathy (Last)

- Ankle and knee jerk absent.
- Extensor plantar reflex +
(D/t spinal cord involvement).
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----- Active space ----- CNS REVISION - 4

DEMENTIA
Major cognitive impairment Affects basic/instrumental activities of daily living.

Diagnostic Criteria :
≥1 of the following 6 impaired :
1. Memory : Medial temporal lobe/ 4. Social cognition : Orbital prefrontal
hippocampus. cortex.
2. Language : 5. Perceptual motor :
- Broca’s (Inferior frontal). Praxicon : Superior parietal lobule.
- Wernicke’s (Superior temporal). 6. Complex attention : Orbital prefrontal
3. Executive function : cortex.

om
Dorsolateral prefrontal cortex.

l.c
ai
gm
Prefrontal Cortex (PFC) :
@
60
23

Medial Orbital Dorsolateral

ik
hv
rit

Energisation and motivation : Associated with : Executive function

|

Disorder Apathy • J : Judgement

w
ro

• I : Insight
ar

•
M

P : Personality, Problem solving

©

• F : Fluency
• A : Abstract thinking, Attention
Causes :
1. Alzheimer’s dementia (M/c). 3. Vascular dementia (3rd M/c).
2. Diffuse Lewy body (DLB) 4. Frontotemporal dementia.
dementia (2nd M/c) : 5. Normal pressure hydrocephalus (NPH).
Part of Parkinson’s plus syndrome. 6. Prion disease.
Note :
10% causes, reversible : Drugs, Vit B12↓, chronic meningitis, autoimmune, normal
pressure hydrocephalus.

Rapidly progressive dementia causes : Young onset dementia causes :

• Frontotemporal dementia. • Frontotemporal dementia.
• Prion disease. • Prion disease.
• DLB dementia. • DLB dementia.
• HIV. • Autoimmune conditions.
• Whipple’s disease. • Chronic meningitis.
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Alzheimer’s Dementia (AD) & Frontotemporal Dementia (FTD) 00:08:23 ----- Active space -----

AD is a Tauopathy.

Etiopathology :
1. Sporadic disease :
Onset >60 yrs.
Defective clearance of Ab amyloid
Apo E4
Ab 40 : Cerebral amyloid
Amyloidogenic Types
Mutated Ab amyloid angiopathy.
pathway
APP gene (Ch. 21) Ab 42 : Alzheimer’s.
Deposition
(Hyperphosphorylated Tau)
Causes neuronal toxicity
Outside neuron Inside neuron

om
l.c
ai
Amyloid plaque. Neurofibrillary (NF) tangles.
gm
@

2. Hereditary disease :
60
23

- Onset <45 yrs (Rare).

ik

- Presenilin 1 (Chr. 14) and Presenilin 2 (Chr. 1).

hv
rit

Note : No proven risk factors exist for Alzheimer’s.

|
w
ro

Disease Progression :
ar
M

4. Non-dominant parietal lobe

©

5. Pre-frontal
cortex 3. Supramarginal gyrus +
Parieto-occipital association areas

1. Hippocampus Visual agnosia

2. Angular gyrus
Stages :
Stage of Area affected Clinical features
Amnesia Hippocampus Episodic memory loss
Gerstmann syndrome :
• Acalculia
Anomia Angular gyrus • Finger anomia
• Rt. to Lt. disorientation
• Alexia with agraphia
Visuo spatial disorientation Non-dominant parietal lobe Visuo spatial disorientation
Executive dysfunction Pre-frontal cortex Executive dysfunction

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 172 Medicine

----- Active space ----- Note :

• Non-dominant parietal lobe dysfunction also leads to constructional apraxia,
dressing apraxia & hemispatial neglect But, these are not seen with
Alzheimer’s.
• Alexia without agraphia Involvement of splenium of corpus callosum.

Treatment :
Cholinesterase inhibitors : Rivastigmine, donepezil & tacrine.
NMDA antagonist : Memantine.

Frontotemporal Dementia (FTD) vs Alzheimer’s :

FTD is also a tauopathy.
Frontotemporal dementia Alzheimer’s disease
Deposition of hyperphosphorylated
Pathogenesis Loss of function of Tau

om
Tau

l.c
APP (Chr. 21) & Apo E4; (Elderly)
ai
Genetic basis MAPT (Chr. 17) gm
Presenilin 1 & 2 (Chr. 1 & 14) (Young)
@
60

Age of onset Young onset M/C Elderly onset (>60 yrs)

23
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Genetic
hv

30% genetic 5% genetic

predisposition
rit
|

Progression Rapidly progressive Slow progression

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Prefrontal cortex involved

ar

PFC involvement Prefrontal cortex first

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at end stage
©

Diffuse Lewy Body Dementia (DLB) 00:19:49

Pathology : α-synuclein Deposition Lewy bodies in the neuronal cytoplasm.

α-synucleinopathies : Parkinson’s, DLB dementia and multisystem atrophy
Clinical Features :
• Years before disease onset :
REM sleep disorders +
ANS dysfunction (Orthostatic hypotension, erectile dysfunction).
• Dementia predominates over rigidity and tremors
(DLB is a Parkinson’s plus disease).
• Visual hallucinations.
• Fluctuating alertness/consciousness.
• Antipsychotics worsen illness.
• No response to L-DOPA.
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Cortical vs Subcortical Dementia : ----- Active space -----

Cortical dementia Subcortical dementia

DLB dementia, NPH,
Examples Alzheimer’s, FTD
Progressive supranuclear palsy.
Severity Severe Less severe
Apraxia/Agnosia/Aphasia + -
Extrapyramidal symptoms - +++
Corticobulbar involvement - ++
Emotional incontinence Less More

Prion Disease 00:27:00

General characteristics :
• Long incubation period. • Young onset dementia.
• No immunity/inflammation. • Rapidly progressive.

om
l.c
• β-pleated sheet of prion PrPsc protein involved.
ai
gm
Creutzfeldt-Jakob Disease :
@

• Dementia + Myoclonus.
60
23

• Cortex Ribboning/spongiform changes.

ik
hv

• EEG : High voltage sharp waves with a low slow background.

rit
|
w

Vascular Dementia
ro

00:28:34
ar
M

Types :
©

1. Post-stroke vascular dementia (Multi-infarct state) S tepwise decline in

cognition.
2. Small vessel stroke (Lacunar stroke) : AKA Binswanger’s disease.
- Pathogenesis : HTN Lipohyalinosis Sub-cortical areas involvement
(White matter disease).
- No step-wise decline of function.
- C/F : Emotional instability + Corticobulbar symptoms + Gait issues +
Urinary incontinence.

Normal Pressure Hydrocephalus (NPH) 00:31:20

Pathogenesis : D/t defective CSF absorption Ventriculomegaly.

C/F : GUD (In order of occurrence).
• Gait disturbance : Apraxia (“Ignition foot” Unable to start walking).
• Urinary incontinence.
• Dementia : Subcortical.
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----- Active space ----- Movement Disorders 00:34:28

Types Hyperkinetic : Chorea, athetosis, hemiballismus, dystonia.

Hypokinetic : Parkinson’s and Atypical Parkinson’s syndromes.
HYPOKINETIC MOVEMENT DISORDERS
Hypokinesia Slowness/paucity of movement with no evidence of
weakness/spasticity.
Parkinson’s Disease :
• >60 yrs (Usually).
• Young onset Parkinson’s :
- PARK 1 (Autosomal Dominant) on Chr. 4.
- PARK 2 (Autosomal Recessive) on Chr. 6.
Clinical picture : Tremor predominant (80%) vs Akinetic rigid (20%, poor prognosis).

om
• Cardinal features : • Gait :

l.c
a. Tremor. a. Flexion hypertonia (Stooped
ai
gm
b. Akinesia. posture).
@
60

c. Rigidity. b. Short steps/festinating gait.

23

d. Postural instability (5-10 yrs c. Reduced arm-swing.

ik
hv

after disease onset). • Other features :

rit
|

• Tremor characteristics : a. Glabellar tap sign + .

w
ro

a. Asymmetric distal : b. Lead pipe/cog-wheel rigidity.

ar
M

Pill rolling tremor. c. Hypomimia & hypophonia.

©

b. 4-6 Hz.
c. Micrographia.
d. ↑ses on concentration.
Atypical Parkinsonism :
Conditions included :
1. DLB dementia.
α-Synucleinopathies
2. MSA.
3. Progressive Supranuclear Palsy (PSP).
Tauopathies
4. Corticobasal Degeneration.
Symptoms : (In contrast to Parkinson’s)
1. Rapid progression.
2. No response to L-DOPA. Common
3. Absence of tremors.
4. Visual hallucinations (DLB).
5. Dementia : <1 yr of disease onset (DLB).
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6. ANS + REM behavioral disorders (DLB & MSA). ----- Active space -----
7. B/L symmetrical axial rigidity (MSA & PSP).
8. Early postural instability Falls (PSP).
9. Gaze palsy (PSP).
10. Myoclonus (Corticobasal degeneration).

Multisystem Atrophy (MSA) :

Types of MSA 1. MSA-P : Parkinson type.
2. MSA-A : Shydrager syndrome (ANS +++).
3. MSA-C : Cerebellar features.
MSA Vs. PSP :
MSA PSP
Pathogenesis α-synucleinopathy Tauopathy
• B/L symmetrical akinetic rigidity (Classical).

om
• Predominant ANS symptoms. • Extensor hypertonia.

l.c
• •
ai
REM sleep disorders. Wide based gait. Frequent falls
Clinical gm
• B/L symmetrical akinetic rigidity (Axial). • Postural instability.
features
@

• Cranio cervical dystonia. • Supranuclear gaze palsy (Downgaze).

60

• Stridor + . • Procerus sign : Wrinkling/furrowing of forehead.

23
ik

• Applause sign : Continuous clapping.

hv
rit

MRI Hot cross bun sign Hummingbird sign; Morning glory sign
|

Corticobasal degeneration : Tauopathy, disease of elderly.

w
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• Asymmetrical involvement.
ar
M

• Triad : Myoclonus + Cortical dementia + Apraxia (D/t superior parietal lobule

©

involvement).
• Hemiballismus and Parkinson’s-like features (D/t basal ganglia involvement).
• Alien limb phenomenon : Disuse of limb d/t motor symptoms.
Agewise Distribution of Movement Disorders :

MSA Parkinson’s PSP CBD

45 55 65 75 85
Age

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 176

----- Active space ----- CNS REVISION - 5

Upper Motor Neurons :

Descending motor pathways.
Components :
1. Corticospinal tract
Cortex Anterior horn cell (AHC).
2. Extrapyramidal tracts
3. Corticobulbar tracts : Cortex Cranial nerve nuclei (Brainstem).
Hence, UMN lesions include lesions of the cortex, subcortex, and the brainstem.
Note : Brainstem lesions Crossed hemiplegia :I/L LMN cranial nerve palsy +
C/L UMN hemiplegia.
Approach to Cortical and Subcortical Lesions 00:04:50

om
CORTEX

l.c
ai
Origin of cortical motor fibres Motor cortex (Area 4) : 30%
gm
Frontal lobe.
@

Premotor cortex : 30%

60

Sensory cortex (Areas 3, 1, 2 parietal lobe) : 40%.

23
ik

• Frontal and parietal lobe lesions C/L hemiplegia seen.

hv
rit

• Temporal lobe (Supplied by M2 inferior division) lesions Wernicke’s aphasia.

|
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• Occipital lobe (Supplied by posterior cerebral A.) lesions  Incongruent C/L

ro
ar

homonymous
M

hemianopia with
©

Blood Vessel Involvement :

macular sparing.
• M1 Artery (Sylvian fissure)
• Superior division of M2 Produce maximum motor weakness.
• Anterior cerebral artery (ACA)
Features of ACA occlusion :
• LL >> UL weakness. • B/L occlusion (Rare) : Severe apathy,
• Gait issues. akinetic rigidity, abulia.
• Bowel/bladder involvement.

Cortical Lobe Lesions :

1. Frontal lobe :
a. Pre-frontal cortex (Orbital, medial, and dorsal PFC) involvement.
b. Frontal eye field Helps in looking at the opposite side (Pts. look towards
c. Broca’s area. the side of the lesion).
d. Motor & pre-motor cortex involvement.
e. Affected in ACA involvement.
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2. Parietal lobe : ----- Active space -----

Dominant Non - Dominant

CLAP : Calculation, Language, Apraxia, Proprioception.
• Angular gyrus : • Visuospatial disorientation.
a. Acalculia, anomia • Constructional apraxia.
b. Left to right disorientation Gerstmann Syndrome. • Dressing apraxia.
c. Alexia with agraphia • Hemispatial neglect
• Superior parietal lobule : Apraxia. (Severe Anosognosia).
• Supramarginal gyrus + Association areas : Visual agnosia.
Note : Inferior quadrantanopia + In parietal lobe lesions.
3. Temporal Lobe :
Medial Lateral Limbic cortex

om
• Responsible for memory • Auditory cortex
Lesion :

l.c
(Hippocampus) • Auditory association areas Auditory agnosia
ai
gm Kluver-Bucy Syndrome
• Epileptogenic area • Wernicke’s area
@
60

Note : Superior quadrantanopia + in temporal lobe lesions.

23
ik

Aphasias :
hv
rit

Indicates dominant hemisphere involvement.

|

Fluency
w
ro

Present Absent
ar
M
©

Sensory aphasia Motor aphasia

Comprehension Preserved Lost Preserved Lost
Repitition Preserved Lost Preserved Lost Preserved Lost Preserved Lost
Transcortical Transcortical Isolation
Type of Nominal Conduction Wernicke Broca’s Global
sensory motor aphasia
aphasia aphasia aphasia aphasia aphasia aphasia
aphasia aphasia (Echolalia)
Note : Naming is affected in all aphasias.

SUBCORTEX
White matter (Internal capsule & corona radiata) with islands of gray matter
(Basal ganglia nuclei).
Internal Capsule (IC) :
• Corticospinal tract passes through posterior limb (Anterior 2/3rd).
• Closely a/w corticobulbar fibers.
• Dense fibers.

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 178 Medicine

----- Active space ----- C/F of IC lesions : Blood supply of IC :

• C/L hemiplegia (Dense). Anterior Posterior
Genu
• C/L UMN CN VII palsy. limb limb
• +/- hemisensory loss.
Upper
• +/- homonymous
MCA
hemianopia.

Lower
ACA ICA Ant. Choroidal

Approach to Brainstem Lesions : Crossed Hemiplegia 00:20:30

om
Midbrain Syndromes :

l.c
m/c vessel involved : P2 segment of Posterior Cerebral Artery (PCA)
ai
gm
1. Ventral midbrain syndromes :
@
60

Weber Claude Benedict

23
ik

Extensive
hv

Site Base of midbrain Tegmentum

rit

(Weber + Claude)
|
w

• I/L LMN CN III palsy

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• I/L LMN CN III palsy • C/f of Weber + Claude

ar

C/f • C/L ataxia/tremor (D/t Dentato-rubro-

M

• C/L UMN hemiplegia • C/L hemiballismus

©

thalamo-cortical fibers)

2. Dorsal midbrain syndromes :

Cause : Pinealoma.
Parinaud Syndrome Nothnagel Syndrome
• Lesion : Tectum.
• C/F : • Lesion : Ventral/anterior to Parinaud.
- Vertical upgaze palsy (Sunsetting sign). • C/f :
- Overactive LPS Lid retraction (Collier’s sign). - I/L LMN CN III palsy.
- Accommodation reflex present + (Pretectal nucleus - Gaze palsy.
Pupillary reflex absent involvement). - C/L ataxia
- Convergence retraction nystagmus. (d/t Superior cerebellar peduncle inv).
- Skew deviation of eyes.

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Pontine Syndromes : ----- Active space -----

Ventral pontine syndrome Dorsal pontine syndrome Lateral pontine syndrome

AKA : Millard Gubler Syndrome AKA : Foville Syndrome AKA : Marie Fox Syndrome
A : I/L Ataxia
F : I/L Facial palsy F : I/L Facial palsy
S : C/L Spinothalamic involvement
S : I/L Sixth nerve palsy G : Gaze palsy
(L/o pain & temperature)
H : C/L Hemiplegia H : C/L Hemiplegia
H : C/L Hemiplegia
Medullary Syndromes :

Lateral medullary syndrome Medial medullary syndrome

• Vessel : Vertebral A. (V4 ) > PICA. • Motor nucleus of CN XII (I/L LMN CN XII palsy).
• Cranial nerves : • Motor fibers of pyramidal tract (C/L Hemiplegia).
- CN V : Spinal nucleus (I/L facial sensations). • �edial lemniscus (C/L posterior column findings).

om
l.c
- CN VII : Nucleus tractus solitarius • Medial longitudinal fasciculus
ai
gm
(Taste, anterior 2/3rd). (Internuclear ophthalmoplegia).
@

- CN VIII : Vestibulocerebellar fibers

60
23

(Ataxia, vertigo).
ik
hv

- CN IX/X : Nucleus ambiguus

rit

(Dysarthria, dysphagia).
|
w

- CN X : Dorsal nucleus of vagus (ANS feature).

ro
ar

- CN XIII : AKA Horner’s Syndrome.

M
©

• Motor : No motor weakness.

• Sensory : Spinothalamic tract
(Loss of C/L pain & temp).
• Cerebellar : Spinocerebellar fibres (I/L ataxia).

Stroke 00:34:50

Brain perfusion :
• Normal : > 22 mL/100gm/min.
• Penumbra : 10-22 mL/100gm/min.
• Infarct : < 10mL/100 gm/min.
Transient ischemic attack (TIA) :
• Neurologic symptoms Return to normal < 24hrs (Usually < 1hr).
• Rx : Dual antiplatelets x 21 days.

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 180 Medicine

----- Active space ----- MANAGEMENT OF STROKE

Suspected case ABCD2 score (Assess risk of stroke) Admit

CT Brain Plain (Rule out bleed) + CT Angio (Localise large vessel occlusion)
MR Angio (Site of lesion)
Thrombectomy : Yes
Thrombectomy possible at institute?
• Only if M1 /PCA involved. No
• Can be done < 24hrs Thrombolysis : Alteplase 0.9mg/kg (10% bolus, rest infusion)
post stroke onset.
Ideal candidate : Contraindications :
• > 18 yrs. • Bleeding episode.
• < 4.5 hrs from onset of disease. • Intracranial Hemorrhage.
• No bleed. • Surgery in the last 14 days.

om
• Edema < 1/3rd of brain territory. • GI bleed in the last 21 days.

l.c
• BP > 185/110 mmHg despite Rx.
ai
gm
Ideal Imaging Protocol :
@
60

Diffusion weighted MRI (DWI) + CT brain :

23

• DWI : Ischemia detected early (30min - 6 hrs) Hyperintense Perform ADC (Apparent diffusion
ik
hv

Hyperintense DWI + hypointense ADC : Stroke. coefficient).

rit
|

• CT Brain : Best to rule out bleed.

w
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DWI Flair :
M

• Shows hyperintensity > 6hrs (DWI : 30min-6 hrs).

©

• Time of stroke can be inferred. (Useful in early morning stroke).

Perfusion MRI : Defines the penumbra (Differentiates ischemic & infarcted area).
MR Angio : Done before thrombolysis/thrombectomy to detect site of occlusion.
Medical Management :
1. Aspirin :
- Given within 48hrs Continued lifelong.
- Low dose : 75mg.
2. Anticoagulants :
- Only indicated in cardioembolic stroke.
- Valvular heart disease, A-fib, mechanical valve Warfarin.
- Rest : Dabigatran.
3. Antihypertensives : Only if BP >220/110 mmHg.
Carotid Endarterectomy : Indicated if carotid atherosclerosis >70% (OR 50-70% with
Note : Role of statins is debatable. symptoms).
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 Nephrology Revision - 1 181

NEPHROLOGY REVISION - 1 ----- Active space -----

Renal anatomy :
3 compartments

Tubulointerstitial (85%). Glomerular (10%). Vascular (5%).

Syndromes in nephrology :

CKD. Renovascular Hematuria Nephritic syndrome.

hypertension. related diseases.

Chronic Kidney Disease 00:01:46

om
l.c
Definition :
ai
Mnemonic : IF TA GS. gm
@

• Interstitial Fibrosis. • Tubular Atrophy. • Glomerular Sclerosis.

60
23

Pathophysiology :
ik
hv

• GFR = Single nephron GFR (snGFR) x No. of functional nephrons.

rit
|

CKD : ↓ no. of functional Compensatory Hyperfiltration Intraglomerular

w
ro

nephrons ↑ in snGFR injury hypertension

ar
M
©

Interstitial fibrosis Interstitial inflammation Proteinuria Alters capillary

(D/t TGF-β). (Protein : Tubulotoxic) pore diameter
Tubular atrophy.
Glomerular sclerosis.
Assessment of GFR :
1. eGFR calculation :
• Factors : • Staging :
- Age. Stage G1 G2 G3 G4 G5
- Race. GFR (mL/min) ≥90 60-89 30-59 15-29 <15
- Sex.
- G1 : Normal GFR + histological/biochemical/
- S. Creatinine.
radiological evidence of kidney disease.
- G5 : End stage renal disease (ESRD).

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 182 Medicine

----- Active space ----- 2. USG :

• Kidney size <8 cm.
8-10 cm + loss in CMD.
• CKD with normal/↑ kidney size :
- Diabetes. - HIV. - Amyloidosis.
PRESENTATION
Diabetic Nephropathy :
Presence of CKD with :
• Hypertension. • H/o diabetes for 5-10 years.
• Extravascular edema • Frothy urine (Long standing).
(Progressive). • Diabetic retinopathy :
• Nephrotic range proteinuria: - 100% T1DM. Develop retinopathy by the
(>3.5g/day). - 65% T2DM. time of developing nephropathy.

om
Note :

l.c
1. Pancreatic diabetes (3c) : Renal impairment present at diagnosis of DM.
ai
gm
2. Nephrotic syndrome : Proteinuria + edema + hypoalbuminemia +
@

hypercholesterolemia.
60
23
ik

Chronic Glomerulonephritis (CGN) :

hv

End stage complication of glomerular disease (M/c d/t IgA nephropathy).

rit
|

Presentation :
w
ro

• Edema. • Proteinuria. • Hypertension.

ar
M

• Uremia (Vomiting). • Frothy urine. • Fatigue.

©

Ischemic/Vascular Nephropathy :
CKD as a complication of renal artery stenosis.
History of : Hypertension + smoking, CAD, PVD.
Investigation : Proteinuria (Trace to 1+), no RBCs in urine.
Chronic Tubulo-Interstitial Disease (CTID) :
• Slow, B/L fibrosis.
• Cause is mostly unknown AKA CKD-U (CKD of unknown cause).
Known causes :
• Drugs : Lithium, calcineurin inhibitors, PPI.
• Autoimmune diseases : IgG4, sarcoidosis, Sjögren’s syndrome.
• Inherited diseases : ADPKD, Medullary Cystic Disease of Kidney (MCDK).
• Reflux nephropathy.
• Obstruction.
• Metabolic disorders : ↑ Ca2+, ↓ K+, hyperuricemia, hyperoxaluria.

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 Nephrology Revision - 1 183

Features : ----- Active space -----

• Slow onset.
• Mostly asymptomatic.
• ± Polyuria & nocturia d/t poor concentrating capacity (Similar to peripheral
diabetes insipidus).
• ↓ Erythropoietin synthesis Disproportionate anemia Fatigue.
• Metabolic acidosis : Renal tubular acidosis type IV Disproportionate ↑ K+.
• Proteinuria - (Bland).
• No edema.

Renovascular Hypertension 00:30:18

Vascular kidney disease :

om
Large vessel related : Small vessel related :

l.c
Renal artery stenosis. • AKA Thrombotic microangiopathy (TMA).
ai
• Eg : HUS Presents as Thrombocytopenia.
gm
@
60

Microangiopathic hemolytic
23

anemia (MAHA).
ik
hv

Renal failure.
rit

Renal Artery Stenosis :

|

Causes :
w
ro

• Atherosclerosis (M/c overall).

ar
M

• Fibromuscular dysplasia (FMD)

©

(M/c in young worldwide).

• Takayasu arteritis (F : M ratio 9 : 1)
(M/c in young in India).
• Polyarteritis nodosa (M/c in young male). String of beads appearance in FMD
Presentation :
• Significant hypertension (Emergency presentation) + complications (Panic
attacks, dyspnea, PRES).
• Significant vascular disease with comorbidities.
• No edema/significant proteinuria.
Investigations :
• CT renal angiography/MR angiography (Definitive).
• USG : Normal sized kidney.
Treatment : Angioplasty & stenting.

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 184 Medicine

----- Active space ----- Hematuria Related Diseases 00:40:25

Hematuria Urological cause (90%).

Nephrological cause (9%).
Hematological cause (1%).
Approach : Hematuria + normal RFT

Urine dipstick

Blood + Blood -

Centrifugation of urine x 5 mins Porphyria.

Assess supernatant

Clear High coloured

om
l.c
RBC + Check after 3-4 hrs

ai
gm
Isomorphic RBC, ≥40% dysmorphic RBC/ High coloured Clear
@
60

No proteinuria, ≥5% acanthocytes /

Hemoglobin +
23

No acanthocytes, 1 single RBC cast + Myoglobin +

(Long t1/2)
ik

No RBC cast proteinuria (Short t1/2)

hv
rit
|

Urological cause (Elderly) : Glomerular cause Acquired intravascular Rhabdomyolysis :

w
ro

• Bladder mass. (Young) : hemolysis : • ↑ CPK.

ar

• Renal cell Ca. IgA nephropathy. Paroxysmal nocturnal • Muscle pain.

M

• Urethral malignancy. hemoglobinuria • H/o sudden

©

(Episodic hematuria). muscular exertion.

Nephritic Syndrome 00:48:51

AKA acute glomerulonephritis/nephritis.

Post Streptococcal Infection Related Glomerulonephritis
Glomerulonephritis (PSGN) (IRGN)/Post infectious Glomerulonephritis
Affected group Pediatrics (2-7 yrs) Adult
Immune status Immunocompetent Immunocompromised (Eg : Diabetic foot)
Incubation period 3-5 weeks Nil
Prognosis Excellent Poor

Causative organism Group A β hemolytic MRSA

streptococci
Renal failure Mildly altered RFT Profound (Requires dialysis)
Starry sky pattern : IgG, C3
Immunofluorescence Rope/garland pattern : IgA, C3 deposits
deposits along capillary wall

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 Nephrology Revision - 1 185

Post Streptococcal Infection Related Glomerulonephritis ----- Active space -----

Glomerulonephritis (PSGN) (IRGN)/Post infectious Glomerulonephritis
Electron
Subepithelial camel hump deposits -
microscopy
Diffuse proliferative
Light glomerulonephritis (DPGN) : Rapidly proliferating glomerulonephritis
microscopy Endocapillary > mesangial proliferation (RPGN) : DPGN + crescent
of neutrophils + no crescent

PSGN :
• Acute onset. • RBC casts + .
• High coloured urine. • Mild edema.
• H/O infection (Skin > throat). • Proteinuria 1+. Common to
• Hypertension + . • Normal S. albumin. PSGN and IRGN
Complications of PSGN :

om
• Hyperkalemia (D/t renal failure).

l.c
• Hypertensive crisis.
ai
gm
• Sudden pulmonary edema (↑ ENaC activation Intravascular volume overload).
@
60

Biopsy in PSGN :
23

Indications :
ik
hv

• Failure of C3 normalisation in 8 weeks C3 glomerulonephritis.

rit
|

• Recurrence.
w
ro
ar
M
©

Granular deposits in PSGN DPGN : Absence of crescent Crescentic glomerulonephritis

Nephrotic syndrome vs. Nephritic syndrome :
Nephrotic syndrome Nephritic syndrome
Onset Insidious Acute
Proteinuria Nephrotic range Mild
Edema Extravascular Intravascular
RFT Normal Deranged (Hyperkalemia)
Albumin ↓ Normal
Lipid ↑ Normal

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 186

----- Active space ----- NEPHROLOGY REVISION - 2

Days to weeks : Rapidly Progressive Renal Failure (RPRF).

Acute renal failure Presents as
Hours to days : Acute Kidney Injury (AKI).
Classification of non-CKD renal disease :

Vascular : Glomerulus : Tubulo-interstitial :

a. Reno vascular a. Asymptomatic. a. Acute Tubular Necrosis (ATN).
hypertension (HTN crisis). b. Nephritic syndrome. - Presents as AKI.
b. Thrombotic c. Macrohematuria. b. Acute Interstitial Nephritis (AIN)
microangiopathy (TMA). d. Nephrotic syndrome. - AKI/RPRF.
e. Rapidly progressive
glomerulonephritis (RPGN).

om
l.c
ai
Rapidly Progressive Renal Failure
gm 00:00:10
@
60
23

Compartment Causes
ik
hv

TMA :
rit

• Adult hemolytic uremic syndrome.

Vascular
|

• Antiphospholipid syndrome.
w
ro

• Scleroderma, HELLP syndrome.

ar
M

Glomerulus RPGN (Clinicopathological disease) : RPRF + crescents on biopsy.

©

Tubulo-interstitium Severe AIN (2° to drug/infection).

RPGN :
Types :
Linear IgG + C3 deposits along GBM :
Goodpasture disease.
Type 1
Type 4 : Double positive (ANCA + &
Anti-GBM + ).
Type 5 : Double negative.
Type 2 Full house effect : SLE.
(Immune complex IgA + C3 : IgA dominant infection
deposits) Related Glomerulonephritis (IRGN). Crescentic glomerulonephritis
Adult Henoch Schonlein purpura (HSP).
Membranoproliferative glomerulonephritis.
Type 3 Pauci-immune RPGN (M/c) : ANCA vasculitis (Microscopic polyangiitis).
In age <20 years : Type 2 > Type 3.

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 Nephrology Revision - 2 187

Features and management : ----- Active space -----

• Volume overload (Facial puffiness + edema ↑↑), high coloured urine (↓ urine
output).
• Ix : RFT (Deranged : Urea ↑, creatinine ↑), ECG, ABG, volume status.
• Mx : Hemodialysis (Uremia) Biopsy (Diagnostic : Crescents +).
F/b
Nephrotic Syndrome 00:12:50

Definition :
• Nephrotic range proteinuria >3.5g/24 hours.
Urine PCR ≥2000 mg/g.
+ >50 mg/kg/day (Children).
• Edema + hypoalbuminemia + hyperlipidemia (Lipiduria).
NEPHROTIC SYNDROME IN CHILDREN

om
Causes :

l.c
• Minimal change disease (MCD) : M/c podocytopathy in children.
ai
gm
• Focal sclerosing glomerulosclerosis (FSGS) : Genetic, podocin mutations + .
@
60

Features :
23

• Onset : 3-4 weeks (Subacute).

ik
hv

• ↓ S. Albumin : Severe extravascular edema + facial puffiness.

rit
|

• N BP, N RFT, hematuria - : MCD.

w
ro

• Hypertension/mild RFT ↑/microhematuria : Likely FSGS.

ar
M

Management :
©

Steroids After 4 weeks Monitor response.

(2 mg/kg/day or 60 mg/m2/day)
Based on response to steroids :
Outcome Further Rx
Complete
-
recovery (25%)
Good response : Infrequent
Steroids (Good recovery)
U. albumin : relapses (25%)
Nil x 3 days FRNS (50%) Cyclophosphamide/
Oral No Rituximab
(Few) mycophenolate mofetil response
SDNS
Genetic FSGS Rx : Transplant
No response/ Biopsy
resistance SRNS Steroid Resistant MCD :
N DOC : Calcineurin inhibitors
(Few cases)
(Tacrolimus > cyclosporin)

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 188 Medicine

----- Active space ----- • SRNS (Steroid resistant nephrotic syndrome) :

Persistent proteinuria despite steroids x 4 weeks.
• FRNS (Frequently relapsing nephrotic syndrome) :
≥2 relapses in 6 months or ≥4 relapses in 1 year.
• SDNS (Steroid dependent nephrotic syndrome) :
≥2 relapses while on tapering dose/within 14 days of stopping steroids.
ADULT ONSET NEPHROTIC SYNDROME
Features :
• Present over 3-4 weeks : Frothy urine + oedema (M/c Pedal).
• N RFT, U. albumin : 3+, no RBCs in urine.
Conditions :
• MCD. • Membranoproliferative
• FSGS : M/c worldwide. Glomerulonephritis (MPGN).
• Membranous Nephropathy (MN) : • IgA nephropathy.

om
l.c
M/c in >60 years. • Amyloidosis.
ai
gm
Secondary causes :
@
60

MCD FSGS MN MPGN

23
ik

• HIV • EBV, CMV • Adenocarcinoma

• Hodgkin’s disease
hv

• Heroin • Parvovirus B19 (m/c : Colorectal) • Infective endocarditis

rit

• NSAIDs
• Obesity • IFN-α • Hepatitis B virus • Plasma cell disorders
|

• Allergy/
w

• Sickle cell anemia • Pamidronate • SLE • Hepatitis C virus

ro

Immunisations
• Hyperfiltration injury • Reflux nephropathy • d-Penicillamine
ar
M

Management :
©

• Biopsy : Mandatory in adults.

Indication : Confirm the diagnosis + rule out 2° causes.
1 1° MCD 1° FSGS MN MPGN
• Thickened GBM
• Mesangial proliferation
Light Focal segmental Thickened GBM
Normal • Lobular structure
microscopy sclerosis (Spike pattern)
• Double contour/
Tram track sign
Immuno - Granular IgG ± C3 deposits
Focal IgM ± C3
fluorescence Normal
deposits Along capillary wall Capillary wall & mesangium
microscopy
Steroids (1 mg/kg) : Ponticelli regime (Steroid
Steroids (Most cases
Rx • Full dose x 6 weeks + cyclophosphamide Treat 2° causes
resistant to Rx)
• Taper x next 6 weeks alternatively x 6 months)
Prognosis Good 2/3 rd
CKD 1/3rd CKD Poor
• Electron microscopy findings in 1° MCD and 1° FSGS : Effacement of podocytes.

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 Nephrology Revision - 2 189

Acute Kidney Injury (AKI) 00:28:04 ----- Active space -----

Causes :
1. Pre-renal : M/c cause of AKI.
2. Renal :
- ATN.
- AIN : Asymptomatic presentation/rash + eosinophilia (Type 4
hypersensitivity).
3. Post-renal : Mostly urological causes.
Pre-renal ATN AIN
• Ischemic (M/c) : 2° to sepsis.
• Drugs (M/c) : Type IV
• Drugs : Mnemonic ACES.
hypersensitivity
Aminoglycosides, Amphotericin B,
• True volume depletion : Mnemonic : BRAND.
Cisplatin, Cyclophosphamide,
Eg : Fluid loss from GI. Beta lactams,
Ethylene glycol,
• Third space loss : Rifampicin,

om
Salicylates, Vancomycin.
Eg : Burns. Anti-convulsants, Allopurinol,

l.c
• Contrast.

ai
• Hypoalbuminemia . NSAIDs,
• Tumour lysis syndrome gm
• Leads to ischemic ATN. Diuretics
(Uric acid nephropathy).
@

• Infections.
60

• Rhabdomyolysis.
• Infiltration injury.
23

• Myeloma cast nephropathy.

ik
hv

Pre-renal AKI vs ATN assessment :

rit
|

Pre-renal AKI ATN

w
ro

• Albumin : Trace/ 1+.

ar

Urinalysis Normal
• Muddy brown epithelial cast.
M
©

U. Na+ ↓ ↑
U. Creatinine ↑ ↓
Fe Na <1% >2%
Urine osmolality 300 mOsm/kg
Urine pH Normal Alkaline
Urine specific gravity 1.010
BUN : Creatinine > 20 : 1 ≤ 10 : 1
Fractional excretion of Na+ :
Fe Na = U. Na+ X Plasma creatinine Normal = 1-2%.
U. Creatinine Plasma Na+
Hypokalemia 00:37:22

Non - renal loss (Intracellular shift of K+; levels : 2.5-3.5 mEq/L).

↓SK +
Renal loss (S. K+ < 2.5 mEq/L) Acidosis.
- Urine K+ ↑. Alkalosis.
- Urine K+ : Creatinine ↑.
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 190 Medicine

----- Active space ----- Acidosis :

Renal Tubular Acidosis (RTA)
Type 1 Type 2
Anion gap Normal Anion Gap Metabolic Acidosis (NAGMA)
Acidosis Severe Mild
Site affected α-intercalated cells of collecting duct Proximal convoluted tubule
Urine pH >5.5 <5.5
Urine calcium ↑↑ (Urinary stone formation) Absent
Rickets + ++
• Wilson’s disease (In young)
• Myeloma (In elderly)
Acquired causes Sjogren’s syndrome • Fanconi’s syndrome :
- In children
- Cystinosis seen

om
Alkalosis :

l.c
Causes :
ai
gm
a. with hypertension :
@

• Conn’s syndrome. • Syndrome of Apparent

60
23

• Liddle syndrome. Mineralocorticoid Excess (AME).

ik
hv

• Cushing’s syndrome.
rit

• Glucocorticoid Remediable Aldosteronism (GRA).

|
w

b. Normal/Low BP :
ro
ar
M

Bartter syndrome Gitelman syndrome

©

Affected site Thick ascending limb of LOH Distal convoluted tubule

Urinary calcium ↑↑ (Stone formation) ↓↓
Hypomagnesemia 20% cases 100% cases
Cannot survive (Seen in children
Prognosis Can survive
only, except Type 3 Bartter)

Hyperkalemia 00:43:38

↑K+ disproportionate to degree Renal failure

and duration of renal failure (M/c cause).

Pseudo In Chronic Tubulo-interstitial RTA 4.

Disease (CTID)
Hypoaldosteronism
Hyper-reninism Addison’s disease.
True
Hyporeninism Diabetes mellitus.
NSAIDS.
β-Blockers.
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 GIT Revision 191

GIT REVISION ----- Active space -----

Malabsorption 00:00:31

Site: Small intestine Proximal : Duodenum, jejunum

Distal : Ileum
STEATORRHEA
• Hallmark of malabsorption.
• Pale, fatty, voluminous, bulky, greasy, malodorous stools.
Investigation :
Quantitative :
72-hour fecal fat estimation : Gold standard.
• 100g fat diet (X 5 days) Stool fat estimation >7g/day : Steatorrhea.

om
On D3-D5

l.c
Qualitative : Sudan III/Sudan black.
ai
gm
DIARRHOEA
@

Most consistent symptom.

60
23

Classification Based on Type :

ik
hv
rit

Osmotic Secretory Factitious diarrhea

|

↑Unabsorbed fats • Toxin-mediated : ETEC, V. cholerae

w

Very low stool

ro

into colon ↑osmolality • Tumor induced : osmolality.

ar

Etiopathogenesis
water influx from epithelial cells VIPoma AKA WDAS/
M

Sample collected
©

Osmotic diarrhea Pancreatic diarrhoea under supervision

Effect of fasting Improves No change shows normal
Stool osmotic gap > 100 mOsm/kg water 25 - 50 mOsm/kg water values.
WDAS : Watery diarrhea achlorhydria syndrome.
• Calculated stool osmolality : 2x stool (Na+ + K+).
• Stool osmotic gap :
- Measured osmolality (Measure with osmometer) - Calculated osmolality.
- N : 50-100 mOsm/kg.
Classification Based on Site :
Small intestinal Large intestinal
• Invasive organism : Shigella, salmonella,
• Osmotic (Chronic)/secretory (Acute)
Causes Campylobacter, Yersinia
• Ileal cause : Crohn’s disease/TB
• Inflammatory : Ulcerative colitis (UC)
Volume of stool Large volume, watery Small volume

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 192 Medicine

----- Active space ----- Small intestinal Large intestinal

Blood/pus/mucus - +
Frequency/urgency/tenesmus - ↑Frequency
Other presentations Ileitis : Pain + Proctitis/proctocolitis

Classification Based on Duration :

• Acute : < 14 days • Persistent : > 14 days. • Chronic : > 30 days.
CLINICAL PRESENTATION
GI symptoms :
1. Diarrhea : Small intestinal type. 4. Ascites (Mild) : D/t hypoproteinemia/
2. Gaseous abdominal distention : hypoalbuminemia.
D/t bacterial fermentation. 5. Unexplained weight loss.
3. Foul smelling stools.

om
Features Causes

l.c
ai
Musculoskeletal symptoms : gm
@

Bone pain, osteopenia, fracture ↓Vit. D, Ca2+

60

Cutaneous symptoms :
23
ik

Hyperpigmentation Vit B12, niacin deficiency

hv
rit

Perifollicular hemorrhage Vit C deficiency

|
w

Acrodermatitis enteropathica Zinc deficiency

ro
ar

Miscellaneous
M
©

Iron deficiency (Proximal SI)

Anemia
B12 deficiency (Distal SI)
• Ataxia :
Posterior lateral cord syndrome : Sensory ataxia Vit B12, E, deficiency
• Peripheral neuropathy
Renal stones Unbound oxalates d/t unavailability of long chain FA
Weight loss Occult malabsorption : SIBO (Small intestinal bacterial overgrowth)

Note : Posterior lateral cord syndrome is also seen in copper deficiency.

Celiac disease, Whipple, & Tropical Sprue 00:18:16

CELIAC DISEASE
All age groups, M = F.
Etiopathogenesis :
Taken up by
Gliadin + IgA dimers Tissue transglutaminase Lamina propria (SI) Deamination antigen presenting
(MALT) cells
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 GIT Revision 193

Presentation : ----- Active space -----

• Classical (50%) : GI symptoms. • Silent : Serology +ve, no symptoms.
• Atypical : Only non GI symptoms. • Latent :HLA DQ2, or DQ8 +ve, serology & symptoms -ve.
Atypical Celiac :
• Iron deficiency anemia • ↑ALT & AST : leads to cirrhosis (Cryptogenic).
(Absorption in proximal SI). • Bone fracture
• Ataxia : A, D, E, K deficiency • Short stature / failure to thrive.

Association :
• Dermatitis herpetiformis. • Microscopic colitis.
• Type 1 DM. • IgA deficiency & nephropathy.
• Thyroid disorders (Hypo/hyper). • Bird fancier lung.
Investigations :
Biopsy : Non-specific

om
Serology :
• Villous atrophy (Total).

l.c
• Anti TTG antibody (IgA) by ELISA :
ai
↑Sensitive, ↑specificity.
gm • Crypt hyperplasia.
• Lymphocytes in lamina propria.
@

• Anti deaminated glutamine dipeptide (IgG) :

60

• Total mucosal thickness remains same.

23

Done in IgA deficiency.

ik
hv

Serology
rit
|

+ -
w
ro

Biopsy
ar

+ Celiac disease
M

No celiac disease
©

- + High suspicion Repeat biopsy

Treatment :
Gluten-free diet (Barley, rye, oats, wheat) Reverts to N biopsy within 6 months.
Refractory celiac : Irreversible after Rx of 6 months.
• Rx Steroids.
• Complications : Enteropathy associated T-cell lymphoma, small cell adeno Ca,
esophageal sq. cell Ca.

WHIPPLE DISEASE
• 50-60 yrs, M > F. Note : Conditions diagnosed with biopsy alone.
• Site : Proximal SI > distal SI. • Agammaglobulinemia • Whipple’s disease.
• Dx : Biopsy. • Abetalipoproteinemia.

Causative organism :
Tropheryma whipplei (Gram +ve, Acinetobacter, not cultured).
- PAS +ve in macrophage.

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 194 Medicine

----- Active space ----- Clinical Features :

CNS (40%) : Joints : Large joint (knee M/c),
• Poor prognosis, relapse + . migratory, intermittent, oligoarthritis.
• Rapidly progressive dementia
(Progressive supranuclear palsy + CVS : Culture negative endocarditis
oculomasticatory nystagmus). (Followed by HACEK organisms).

GIT : Features of malabsorption + lymphadenopathy, abdominal pain (D/t ileitis).

Treatment :
• Ceftriaxone/meropenem : For 14 days.
• Cotrimoxazole : Crosses BBB & prevents relapse.
TROPICAL SPRUE
M/c cause of malabsorption in Asia.
Etiology :

om
Coliform infection Toxins & fermentation products released Triggers tropical

l.c
(E. coli, Klebsiella) sprue
ai
gm
Clinical Features :
@
60

• Pan-intestinal : Ileal involvement mainly. • Spares other systems.

23

• Hyperpigmentation d/t B12 deficiency.

ik
hv

Neurological features : Rare.

rit
|

Management :
w
ro

Biopsy : Similar to celiac disease with partial villous atrophy.

ar
M

Rx : Folic acid + Tetracycline.

©

Inflammatory Bowel Disease 00:32:36

• Bimodal peak : 15-30 yrs, 70-90 yrs. • M > F, CD > UC • Ethnicity :Jewish (M/C).
Crohn’s disease (CD) Ulcerative colitis (UC)
OCP + (F > M) -

Associations SMoking Causative

Protective
Appendicectomy Unrelated
Familial CD > UC
Antibiotics use < 1 yr of life Strong associations
• Turner syndrome (M/c)
• IL-10 receptor defect : Childhood IBD (Refractory/drug resistant)
• Wiscott Aldrich syndrome
Syndromes associated - Recurrent sinopulmonary infection
• Hermansky Pudlak - Thrombocytopenia : Microplatelets
• Von-Gierke (GSD-1) • IPEX : Immune polyendocrinopathy X-linked syndrome
- D/t FOX-P3 mutation (T-regulatory cells defect)
- Dematitis, UC, endocrine (Type 1 DM)
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 GIT Revision 195

----- Active space -----

Crohn’s disease Ulcerative colitis

• NOD2/CARD 15 gene Defective innate immunity
Etiopathogenesis • Retention of M. paratuberculosis Th2 cells involved
• Th1/Th17 cells involved
• Rectum (M/c)
• Mouth to anal • Proctitis/Proctosigmoiditis
Site involved
• Ileocolitis (M/c) • Pan-colitis
• Backwash ileitis (Rare)
Constitutional
+ -
features
• Diarrhea
• Large intestinal diarrhoea
Clinical • Abdominal pain (D/t ileitis)
• Fresh bleeding PR
features • P/A : Inflammatory mass
• Blood streaks on hard stool surface
• Malabsorption features (In jejunal involvement)

om
• Superficial, continuous

l.c
• Transmural, segmental
• Symmetrical
ai
• Asymmetrical gm
• Erythematous mucosal surface (Early)
Lower GI • Aphthoid ulcers (Deep)
@

↓Vascularity Friable ulcer

60

endoscopy • Rose thorn ulcer

• Pseudo polyp (Inflammatory masses)
23

• Cobblestone pattern
• Lead pipe appearance
ik

• String sign (Circumpressure fibrosis)

hv

• Deep collar button ulcer

rit

• Colonic thickening in CT
|

Radiological • Fine mucosal granularity (Earliest)

w

• Creeping mesenteric fat

ro

features • Serrations
ar

• Fat halo sign

M

Marker Calprotectin
©

Biopsy Granuloma -

• Bowel obstruction
• Stricture (Jejunoileitis)
Toxic
Complications • Fissure
megalcolon
• Fistula : Enterovesical
• Fibrosis

Response to
+ -
antibiotics
Recurrence
+ -
after Sx
• Ankylosing spondylitis
• Uveitis
Extraintestinal Primary sclerosing cholangitis (PSC)
• Cholelithiasis, nephrolithiasis
manifestations • Thromboembolism
Pyoderma gangrenosum

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 196 Medicine

----- Active space -----

Crohn’s disease Ulcerative colitis

• Erythema nodosum
Features associated
• Episcleritis
with relapse
• Large joint migratory, asymmetrical pauciarthritis (Knee : M/C)
• ASCA : A/w complication
• OMP-C (Outer membrane protein- citrullinated) • Anti-goblet cell antibody
Serology • APB (Anti-pancreatic antibody) • p-ANCA (Seen in PSC) : ↑Risk
• Anti-flagellin of cholangiocarcinoma
• Anti-12: ↑Risk of surgery.
Features of Ulcerative Colitis :

om
l.c
ai
@
gm Endoscopy (Mayo criteria)
60
23
ik
hv
rit
|

Lead pipe colon

w
ro
ar
M

Absent haustral markings Pseudopolyps Collar stud appearance

©

Features of Crohn’s Disease :

Cobble stoning Colonic thickening Creeping mesenteric fat

Fat halo sign Rose thorn ulcer String sign

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 GIT Revision 197

Irritable Bowel Syndrome (IBS) 00:47:17 ----- Active space -----

• Functional disorder.
• < 45 yrs, F > M.

Clinical Presentation : 1. Defecation.

• Recurrent abdominal pain A/w 2. Change of frequency of stools :
Lower GI cramping type. Alternating diarrhoea with constipation.
• Nausea/vomiting. 3. Change in appearance of stools.
• Mucus in stools.

Exclude IBS if :
• > 45 yrs at first presentation.
• Anemia.
• Fever, ↑ESR.

om
• Nocturnal diarrhea, steatorrhea, bloody stools.

l.c
• Small bowel pathology.
ai
gm
• Weight loss.
@
60

Management :
23
ik

• Low FODMAP diet.

hv
rit

IBS-C IBS-D
|
w

(Conspitation predominant) (Diarrhea predominant)

ro
ar

• Chloride channel activator : Lubiprostone. • Loperamide.

M

• Guanylyl cyclase agonist : Linaclotide. • μ receptor agonist :

©

• Na-H exchanger : Tenapanor. Eluxadoline.

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 198

----- Active space ----- HEPATOLOGY REVISION

Acute Hepatitis 00:00:27

Viral prodrome : 1-2 days Disease : Recovery.

• Malaise. • Jaundice.
• Vomiting. • ALT, AST : >1000 IU/L Hepatic Fulminant.
• Hypoglycemia. (ALT > AST). failure Acute.
Etiology :
• Virus : Hep A (M/c in children), Hep E (M/c), Hep B.
• Drug Induced Liver Injury (DILI) :

om
- Dose dependent : Paracetamol.

l.c
- Dose independent : Idiosyncracy (Rifampicin), hypersensitivity
ai
gm
(Carbamazepine, phenytoin, azathioprine, propylthiouracil, valproate, INH).
@

• Toxin : Alcohol (Poor prognosis), rat killer poison (Zinc oxide).

60
23

• Ischemic.
ik
hv

• Wilson disease/autoimmune hepatitis/Budd-Chiari syndrome.

rit

• Acute fatty liver in pregnancy.

|
w

Hep A v/s Hep E :

ro
ar
M

Hep A Hep E
©

Incubation 30 days 40 days

Feco-oral
Route of transmission
Never vertical Never parenteral/sexual
Pathophysiology Cytotoxic effect Immune-mediated (Cholestatic phase + )
Risk of liver failure 1 in 2,00,000 0.5-2%, 20% in pregnancy
Rx Supportive
Chronicity -
Note : HBV + HDV 5-20% risk of hepatitis.
Liver Failure (Complication) :
• Based on time of presentation since jaundice : • Other features :
- Fulminant failure : <7 days. - Lactic acidosis.
- Acute failure : 7-21 days. - Sepsis/MODS.
• Coagulopathy + encephalopathy. - Acute Tubular Necrosis (ATN).
(INR ≥ 1.5) (Acute ↑ NH3 ↑ ICT). - Hypoglycemia/hyponatremia.

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 Hepatology Revision 199

Treatment : ----- Active space -----

• Supportive.
• Glucose supplementation : 150 g using 10% dextrose.
• Transplant : In liver failure.

PARACETAMOL POISONING
Toxic dose : >7.5 g.
Time since dose Features Treatment
24 hrs Nausea, vomiting. • Charcoal hemoperfusion :
• Enzyme ↑, PT ↑. Within first 4 hrs.
24-72 hrs
• Abdominal pain. • N-acetyl cysteine (100 mg/kg) :
72-96 hrs Fulminant hepatic failure. Within first 16 hrs.

Chronic Hepatitis 00:08:20

om
Etiology :

l.c
ai
• Non-alcoholic steatohepatitis (NASH). gm
• Chronic viral hepatitis : HBV, HCV.
@
60

• Autoimmune : SLE.
23
ik

• Hemochromatosis (Bronze pigmentation, small joint arthritis, pancreatic DM,

hv

dilated cardiomyopathy, hypogonadotropic hypogonadism).

rit
|

• Wilson’s disease : Age <20 yrs.

w
ro

Investigations : Clinical features :

ar
M

• ALT, AST : ↑ (<150 U/L). • Asymptomatic usually.

©

- ALT > AST : Chronic hepatitis. • Wasting of muscle, fatigue.

- AST > ALT : Cirrhosis. • Altered sleep pattern.
• Fibroscan (Transient elastography) : For • ↓ libido.
cirrhosis.
• MR elastography.

Progression :
Portal HTN :
• Variceal bleed.
• Ascites.
Any 1 +
Chronic Compensated • Hepatic encephalopathy.
hepatitis cirrhosis Liver failure : Decompensated
• Jaundice. liver disease.
HCC.

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 200 Medicine

----- Active space ----- Pathophysiology of Portal HTN :

↑Portal pressure : ↑Flow X ↑Resistance
d/t
d/t
↑Systemic NO ↓ SinusoidalNO : Lobules Nodules
+
• Sinusoidal vasoconstriction. Fibrous
Sphlanchnic vasdilation : • Sinusoidal defenestration. septations
• ↑Peripheral resistance Hyperdynamic circulation.
• ↓Effective circulatory vol. salt/water retention ↑sinusoidal/portal v. pressure
RAAS +
Ascites
Compensation : ↑splenic vein pressure :
Portosystemic collaterals • Splenomegaly
(can lead to varices) • Hypersplenism :
Complications : Thrombocytopenia
Portal HTN : Liver failure :

om
• Thrombocytopenia : Earliest lab finding. • Jaundice.

l.c
• Splenomegaly : Earliest clinical finding. • Alopecia.
ai
gm
• Varices (Endoscopy) : D/t portosystemic • Dupuytren’s contracture. Alcohol induced.
@
60

collaterals. • Parotid swelling.

23

• Ascites : SBP, Hepatorenal syndrome (HRS). • Palmar erythema, hyperpigmentation.

ik
hv

• Hepatic encephalopathy. • Gynecomastia.

rit

• Testicular atrophy. D/t ↓ estrogen & defective

|
w

5α reductase.
ro

• Caput medusae.
ar
M
©

Hepatitis B & C 00:22:20

HEPATITIS B
HbxAg (+)

Acute hepatitis 1-5% Chronic hepatitis Cirrhosis HCC.

(Sexual or parenteral (Vertical transmission) : Liver failure.
route) : • Anti Hbc IgG +ve. P HTN.
• HbsAg +ve. • HbsAg +ve.
• HbeAg +/-
Reactivation (Acute on Chronic)
• Anti Hbc IgM : Most
specific marker.
Recovery
10-30 yrs
• HbsAg -ve. Immune tolerance Immune clearance Inactive carrier phase :
phase : (No inflammation) phase : • HBV DNA : Low
• Anti Hbs +ve.
• HbeAg -ve. • HBV DNA ↑. • HBV DNA ↓↓. (<2000 IU).
• Anti HBc IgM +ve. • Hbe Ag +ve. • Jaundice. • Hbs Ag +ve.
• ALT, AST : Normal. • ALT, AST : ↑. • Hbe Ag -ve.
• ALT, AST : Normal.

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 Hepatology Revision 201

Acute v/s Acute On Chronic Hepatitis : ----- Active space -----

Acute hepatitis B Acute on chronic hepatitis B

Etiology Needle prick Reactivation of carrier
HbsAg +ve +ve
HbeAg +/- +ve
Serology HBV DNA <2000 IU ↑↑↑
Anti Hbc IgM +ve +ve
q HbsAg +ve
Symptoms Severe
Progression to cirrhosis <5% High risk
Treatment :
Acute Chronic

om
• Supportive care. Cirrhosis + Cirrhosis -

l.c
• Indication for Rx :

ai
- INR ≥1.5. gm
• Hbe Ag +ve.
Treat • Hbe Ag -ve.
- Jaundice : >3 mg/dL.
@

• HBV DNA >20000 IU. • HBV DNA >2000 IU

60

- Duration : ≥4 wks.
(Pre-core mutant).
23
ik
hv

Tenofovir alafenamide Treat if ALT >2 times N values.

rit

Serological Patterns :
|
w
ro

HBsAg Anti HBs Anti HBc HBeAg Interpretation

ar
M

+ - IgM + Acute hepatitis, high infectivity

©

+ - IgG + Chronic hepatitis, high infectivity

Acute hepatitis with high infectivity :
+ - IgM -
Pre-core mutant (Does not produce HBeAg)
- - IgM - Acute hepatitis
- - IgG - Remote infection
- + IgG - Recovered from acute hepatitis
- + - - Vaccinated
HEPATITIS C
Progression :
85% HCC.
Acute hepatitis Chronic hepatitis : Cirrhosis
Asymptomatic (Anicteric) : • Anti-HCV +ve. Liver failure.
• Anti HCV +ve. • HCV RNA +ve. Portal HTN.
• HCV RNA +ve.
Extra hepatic manifestations :
• Sjögren’s syndrome. • Lichen planus.
• Cryoglobulinemia. • MPGN.
• Porphyria cutanea tarda.

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 202 Medicine

----- Active space ----- Treatment :

• NS5A Inhibitors + NS5B Inhibitors x 12 weeks.
Velpatasvir Sofosbuvir
• Add Ribavirin : If cirrhosis + .

Autoimmune Disorders 00:35:49

AUTOIMMUNE HEPATITIS
Type 1 : Lupoid hepatitis.
• M/c in females.
• 2nd & 3rd decade.
• A/w SLE.
Pathogenesis : Clinical Presentation :
• Lymphoplasmacytic • Acute hepatitis + waxing & waning jaundice.

om
infiltrate. - Polyclonal hypergamma globulinemia.

l.c
• Interface hepatitis : B/w • Chronic hepatitis.
ai
gm
portal tract & hepatocyte.
@

• Emperipolesis.
60

Histologic features.
23

• Rosette formation.
ik
hv

Antibodies :
rit
|

Type 1 : Type 2 :
w
ro

• ANA. • LKM-1 (Also in Hep C).

ar
M

• SMA (Smooth muscle Ab). • ALC-1.

©

• AAA (Anti-actin Ab) : Poor prognosis. Note :

• Anti SLA (Soluble liver Ag) : Most specific. LKM-2 : Drug induced.
• Atypical p-ANCA. LKM-3 : Hep D infection.
PBC v/s PSC :
PBC (10 biliary cirrhosis) PSC (1o sclerosing cholangitis)
Host Middle aged female. Young male.
Autoimmune inflammatory Fibrosing destruction of intra
Pathology
destruction of intrahepatic bile duct. & extrahepatic bile ducts.
• Sjogrens syndrome.
Association • Distal RTA. Ulcerative colitis.
• Xanthoma/xanthelasma.
Antibodies AMA (Antimitochondrial Ab). Atypical p-ANCA.
Intrahepatic cholestasis + +
Symptoms Fatigue, pruritis.
Investigation ALP↑↑. MRCP (IOC), ERCP.
Rx Ursodeoxycholic acid. Transplant.
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 Hepatology Revision 203

Wilson’s Disease 00:41:24 ----- Active space -----

Gene : ATP 7b (Wilson’s ATPase) of chromosome 13q.

Age : 3 - 20 yrs.
Pathogenesis :
• Failure of Cu2+ to incorporate Degrades ↓ ceruloplasmin in serum
into ceruloplasmin ceruloplasmin : <10 mg/dL.
• Defective biliary excretion of Cu.
• Copper levels :
- Total S. Cu ↓↓.
- Non-ceruloplasmin bound Cu : Urinary & free Cu ↑↑ Hepatic &
neurological symptoms.
- Ceruloplasmin bound Cu ↓↓↓.

om
Investigation :

l.c
• ↓ S ceruloplasmin : Marker.
ai
gm
• Liver biopsy.
@

Gold standard.
60

• Quantitative Cu estimation.
23
ik

Clinical Presentation :
hv
rit

Hepatic : CNS :
|
w

• Acute hepatitis : ALP ↓ + • Dysarthria (M/c).

ro
ar

Coomb’s -ve hemolytic anemia. • KF ring in descemet’s membrane :

M

• Chronic hepatitis : Non-specific.

©

- <20 yrs + non-specific - 95% in neuro Wilson.

symptoms. - 60% in hepatic Wilson.
- Fatty liver. • Psychiatric symptoms.
- Asymptomatic ALT/AST ↑. • Parkinson’s symptoms.
• Cirrhosis. • Dystonia & posturing : Risus
• Decompensated liver failure. sardonicus.
• Jaundice. • Wing beating tremor.

Note : KF rings Also seen in cholestasis.

Others :
• Hypoparathyroidism. • Hemolysis.
• Pancreatitis. • Infertility/recurrent abortion.
• Amenorrhoea. • Type 2 RTA.

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 204 Medicine

----- Active space ----- Treatment :

d-penicillamine : DOC.
- Started at 250 mg Dose ↑ 1.5 g : Prevents w
 orsening of neurological
symptoms.
- S/E : Myasthenia, membranous nephropathy, drug induced lupus
erythematosus, aplastic crisis.
• Trientere.
• Zinc : Release ↑ metallothionein ↑ Cu sequestration.

Hemochromatosis 00:48:00

• Age : >40 yrs.

• HFE gene of Chromosome 6p.
• Pathogenesis d/t unregulated iron absorption.

om
Clinical Presentations :

l.c
• Chronic hepatitis : • Bronze grey pigmentation.
ai
gm
- Cirrhosis. • Type 3c DM : Pancreatic diabetes.
@
60

- Hepatomegaly : Alcohol ↑ risk. • Dilated cardiomyopathy.

23

• Hypogonadotropic hypogonadism.
ik
hv

• Non-inflammatory arthritis of Irreversible.

rit
|

2nd & 3rd MCP joints.

w
ro

• Hook-like osteophytes.
ar
M
©

Management :
• Investigation :
- Serum ferritin + transferrin saturation ratio : ↑↑.
- C282Y mutation : Gold standard.
• Rx : Phlebotomy.

Decompensated Liver Disease 00:54:34

Decompensation :
• Variceal bleed.
D/t portal HTN.
• Ascites : Earliest sign.
• Jaundice d/t liver failure.
• Hepatic encephalopathy.

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 Hepatology Revision 205

ASCITES ----- Active space -----

Serum Ascitic Albumin Gradient :

SAAG = S. albumin - ascitic fluid albumin

< 1.1 (Low SAAG) ≥ 1.1 (High SAAG)

Low protein High protein Low protein High protein

Nephrotic Peritoneal Portal HTN Budd Chiari

syndrome carcinomatosis syndrome
Treatment of Ascites :
Grade Mx
Grade 1 Salt restriction <2g/day.
Spironolactone 100 mg/dL (Max : 400 mg/dL) +

om
Furosemide 40 mg/dL (Max : 160 mg/dL)

l.c
Grade 2
ai
No response gm
@

Diuretic resistant ascites TIPSS.

60
23

Grade 3 Large volume paracentesis No response

ik

TIPSS.
hv

TIPSS : Transjugular intrahepatic portosystemic shunt.

rit
|

Refractory ascites :
w
ro

• Diuretic resistant ascites : • Diuretic intolerant/

ar
M

- No response after max dose. Intractable ascites :

©

- Rx : TIPSS. Not tolerating drug.

Spontaneous Bacterial Peritonitis (SBP) :
• Ascitic fluid WBC :>500 cells/μL or PMN >250 cells/μL in absence of surgically
+ treatable source of infection.
Culture +ve : E. coli (M/c).
• Danger signs : Abdominal pain, fever with chills, sepsis.

Variants :
• Monobacterial non-neutrocytic ascites (MNNA) : Gram +ve. Mild.
• Culture negative neutrocytic ascites (CNNA).

Treatment :
• Inj. Ceftriaxone 2g IV TDS x 5 days.
• Prophylaxis : Norfloxacin 400mg.

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 206 Medicine

----- Active space ----- Hepatorenal Syndrome (HRS) :

• Functional kidney disease : Pre-renal failure + unresponsive to fluids.
• No structural kidney disease (KFT : N , except creatinine).
• D/t splanchnic vasodilation Intrarenal vasoconstriction.
Treatment :
• Transplant.
• Terlipressin OR
• Norepinephrine OR Vasoconstrictors : If planned for transplant.
• Subcutaneous octreotide
+
Oral midodrine.
Hepatopulmonary Syndrome (HPS) :
Clinical features : Pathophysiology : Splanchnic vasodilation
• Cirrhosis with portal HTN. Intrapulmonary vasodilation, A-V

om
• Dyspnea. connections V/Q mismatch

l.c
• Clubbing. Hypoxia.
ai
gm
• Platypnea (Dyspnea on standing)/ Investigations : Bubble ECHO.
@

Orthodeoxia (↓ in O2 saturation). Rx : Transplantation.

60
23
ik
hv

HEPATIC ENCEPHALOPATHY
rit

Reversible portosystemic encephalopathy (Type C).

|
w
ro

Note :
ar

• Type A : Encephalopathy d/t fulminant hepatitis.

M
©

• Type B : TIPSS.
Pathophysiology :
Undetoxified ammonia + Other ammonia related products : Mercaptans,
phenol, manganese, aromatic amino acids.
Astrocytes Toxic
NH3 + Glutamate Glutamine 2° neuronal injury.
• High in CSF.
• Bind to NMDA receptors.
Precipitating Factors :
• Alkalosis : • ↑ NH3 production :
- Hypovolemia, vomiting, - Sepsis.
dehydration. - UGI bleed.
- Hypokalemia. - ↑ protein intake.
• Renal failure. - Constipation.
• Benzodiazepines.
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 Hepatology Revision 207

West Haven Criteria : ----- Active space -----

Grade Characteristics
Minimal
Covert HE • Short attention span. Evaluation : Psychometric test
1
• Sleep disturbance.
2 • Personality & behavioral change, asterixis.
• Disorientation, clonus, rigidity, hyperreflexia.
3
Overt HE • Responsive to pain.
• Comatose.
4
• Triphasic wave on EEG.
Treatment :
• Lactulose bowel wash : ↓ pH of lumen ↑ NH4+.
• Rifaximine.
• LOLA.

om
HEPATIC VENOUS PRESSURE GRADIENT (HVPG)

l.c
ai
• HVPG = Wedged HVP - free HVP. gm
• Sinusoidal pressure : >6 mmHg
@

Pathology + .
60
23

Cause WHVP FHVP HVPG

ik
hv

Pre-hepatic EHPVO N N N
rit

Intrahepatic Cirrhosis ↑ N ↑↑↑ EHPVO : Extrahepatic

|
w

portal vein obstruction.

ro

Post-hepatic Budd Chiari ↑ ↑ N

ar
M
©

Important Formulae 00:49:58

Anion Gap :
• Serum anion gap : Na+ - (Cl- + HCO3-).
• Urine anion gap (UAG) = Unmeasured anions - unmeasured cations.
NAGMA : Normal anion gap metabolic acidosis.
• Loss of HCO3- is compensated by Cl-.
• Seen in RTA, VIPoma.
- RTA : H+ not excreted ↓ NH4+ in urine UAG +ve.
HAGMA : High anion gap metabolic acidosis.
• ↑ in unmeasured anions (Keto acids, lactic acid, uremic toxins, alcohol).
• Anion gap ∝ Unmeasured anions.

Stool Osmotic Gap :

• Measured stool osmolarity - 2 (Na+ + K+).
• ↑osmotic gap = osmotic diarrhea.
Medicine Revision • v4.0 • Marrow 8.0 • 2024