1 CARDIOVASCULAR SYSTEM

ELECTRO CARDIOGRAM (ECG)

• Discovered by : Karl Einthoven

• It Records electrical activity of heart using electrodes/leads.

ECG Waves and periods

1. P-WAVE
• Due to Atrial Depolarisation.

• Positive Wave.

• Absent in Atrial Flutter and Atrial Fibrillation.

• Also Absent in Ventricular Arrhythmia (PSVT,VT,V.Fibrillation).

• P Pulmonale : Right Atrial Hypertrophy.

• P-Mitrale : Wide P-Wave and Double Peak (Left Atrial Hypertrophy).

 P-Pulmonale P-Mitrale

2.5mm

0.12 Sec.

2. QRS-COMPLEX
• 3 waves.
• Indicate Ventricle Depolarisation.
• The normal duration of QRS : < 0.11second or 110 milliseconds.
• Normal QRS : <3 boxes.

3. Q-WAVE
• Small Negative Wave.
• Due to Inter-ventricular Septal Defect.
• Mostly Absent in all leads except V5 and V6.
• Q-Wave in other leads are mostly Pathological.

Eg : BBB,MI,Old Infarct, Pulmonary Embolism.

4. R-WAVE
• Big Positive wave.
• Due to Depolarisation Of Maximum Bulk of Ventricle.
• It gives Ventricular Hypertrophy.(Left Ventricular
Hypertrophy)
- That is : Big R-WAVE Hypertrophy.
5. S-WAVE
• Last wave of Ventricular Depolarisation.
• Small negative wave due to : Depolarisation of Posterio-Basal Part of left
ventricle.

6. T-WAVE
• Big Positive Wave after QRS.
• It occur due to Ventricle Repolarisation (K ions) that is the Reason T-Wave
is affected in K ion imbalance.
• Tall T-Wave : HYPERKALEMIA.
• Small T-Wave : HYPOKALEMIA.

EXTRA EDGE
1. J-wave/ Osborn wave/ Camel hump wave : seen in Hypothermia.
• It is Sharp Spike between QRS and T-Wave.

2. U-Wave :
• Small Positive Wave due to Repolarisation of Purkinje Fibre
(Papillary muscle)
• Seen in : MI, Ventricular Hypertrophy, Digoxin Toxicity.
Electrolytes Imbalances (Hypokalaemia, Hypercalcemia).
SEGMENT
• Isoelectric.
• Straight line.

1. ST-Segment :
• Start with end of S-wave and start of T-wave Start with J-Point.

ST-Elevation:
• Hyperkalemia,Myocardial infarction,variant Angina,Pericarditis.

ST-Depression:
• Myocardial Ischemia,Digixin toxicity
INTERVAL
• Waves.

1. PR Interval :
• Induce P-Wave
• Start with P-wave till start of QRS
• It indicates the time taken for impulse to travel from Atria to ventticle via
AV node
• NORMAL PR interval =. 0.12 to 0.16 sec (120-160msec)
• 3-4 nixes(1mm=0.4sec)
• PR interval >0.20sec -Seen in AV block
• PR interval <0.12sec -Seen in WPW syndrome

2. QT Interval :

• From start of QRS till end of T-Wave.

• Includes all waves except P-Wave.
• QT Interval : QRS and T-Wave.
• QTc Interval : Corrected QT interval (Normal- 0.36-0.44sec 9-11 boxes)
• Interval QTc : Seen in Hypokalemia, Hypocalcemia, Hypothermia and also
Seen in class - Ia and III anti arrythmic agent. (Slow heart beat and conduction).
• Drugs like Ketoconazole and Cisapride also shows Increased QTc.
• Increased QTc will increase the risk of ventricular arrythmia :
Torsades de Pointes. Its a polymorphic ventricular Tachycardia (Rx - MgSO4)
causes : Twisting of QRS.
 Torsades de Pointes :

ECG LEADS

• 12 leads to see heart from all directions.

1. VERTICAL PLANE : (Up and Down) : Limb lead 6.

• Bipolar : I, II, III.
• Unipolar : (Right arm) aVr.

2. HORIZONTAL PLANE :
• Anterior and Posterior: They are Precordial (V1-V6).
• Chest lead : (Left Arm) aVL ; (Foot) aVf.
• Posterior leads : V7,V8,V9.
 • In V1 and V2 : S>R.
• In V3 and V4 : S=R.
• In V5 and V6 : small or no S (R>S).

In Right Ventricular Hypertrophy :

• V1 and V2 : R>S.
• V5 and V6 : Big S-Wave.

In Left Ventricular Hypertrophy :

• V1 and V2 : Big S-Wave (>30mm).
• V5 and V6 : Very Big R-Wave (20mm).
 LIMB LEAD

ENTHOVEN TRIANGLE:
• Left axis deviation
- Rmax in lead I>II,III(small or -ve)
- Causes : Obese, Pregnancy, LVH, LBBB.

• Right axis deviation

- Rmax in Lead III>I.II(small or -ve)
- Causes : Slim, Standing, RVH, RBBB.

CONDUCTION DEFECT

1. AV BLOCK
• MCC : Vagus
- Also : MI,Ischemia,Drugs,Infections
• DOC-Atropine(DOC For sinus bradycardia,Vasovagal reßux,OP poisoning).

Three degrees of AV block :

A. Ist degree AV block :
• Only increase in PR Interval (>0.20 second), but no dropping of beats.
• P : QRS ratio is 1:1.

B. IInd degree AV block :

• Missing beat/dropped QRS.
• P : QRS ! 1:1
• AKA : Mobitz Block.
• Mobitz II can lead to IIIrd Degree or complete heart block i.e, IIIrd heart block-
No relationship b/w P and QRS (independantly beating).

2. WOLF PARKINSON WHITE SYNDROME (WPW)

• Bundle of Kent! Bypass AV node ! Impulse reaches ventricles faster

!

Cause depolarization of ventricle

• Also wide QRS >0.11sec (>3boxes) [lambda wave-early depolarization]

• Lead II- best for rate rythm,interval etc..
• Lead III -for axis
• V1,V2,V5,V6 : for Hypertrophy and BBB.

• DOC : Class Ic antiarrythmic

-Flecanide
-Propatenone
• Treatment of choice : Catheter radiofrequency ablation of Kent.
Because kent can cause re entry or circus movement and cause PSVT.

3. BUNDLE BRANCH BLOCK

• It can be left bundle or right bundle.
• Increased QRS duration >0.11sec(>3box).
• Same side axis deviation.
• RAD in RBBB.
• LAD in LBBB.
• T-wave changes -inversion of T wave.
• Slurring or notching of QRS(M or W pattern).

RBBB LBBB
 ATRIAL ARRYTHMIAS
1. Atrial ßutter
¥ No P wave but replaced by sharp ßutter waves. Saw tooth pattern 4:1 ratio

2. Atrial Fibrillation
¥ P wave absent,rather irregular Þbrillating activity.
• Normal QRS width but irregular rythm(R-R interval not constant).

Clinical Feature :
• Palpitation.
• Fainting.
• Syncope.
• Irregularly irregular pulse.

Treatment :
• DOC: Class III anti arrythmic( for rythm control) : Dofetilide > Ibutilide
• For rate control! beta blockers, CCB.
¥ If patient of A.Þb has low BP or shock,hemodynamically unstable :
Cardio version with DC shock.
• Atria not contracting properly so,blood had stasis and increased risk of
thromboembolism : • Always use Anticoagulants.
• Oral warfarin.
• IV LMW heparin(Enoxaparin).
 SUMMARY

CORONARY ARTERY DISEASE

Blood supply of heart :

Aorta

RCA LCA

Supply : Inferior wall. Circumßex

LAD
• Leads Used-I,III,Vf.
• Left ant.division • Lateral
 • In CAD- narrowing/stenosis of coronary artery(one or multiple).
• MCC of CAD : Atherosclerosis
Others cause : Vasospasm, Drugs, Emboli, Infections.
• Risk factors : obesity,DM.Dyslipidemia,alcohol,smoking,sedentary lifestyle
• MC vessel involved in CAD : LAD (left anterior division)Also known as :
Widow’s artery.
• Coronary artery disease is MC in males.
• In females, Estrogen is protective for CAD ,but after Menopause,same amount of
risk.
Clinical Feature :
¥ Low blood ßow cause Myocardial Ischemia.
• Left retrosternal chest pain-Angina pectoris.
• Pain radiates to left arm and shoulder.
• Clenched over chesg : Levine sign.
• Sweating,palpitation, due to increased HR,but Decreased HR in inferior
wall MI.

Treatment :

• Sublingual nitrates.
• Isosorbitrate, Isosorbide
¥ Since nitrates have high Þrst pass metabolism its given sublingually.
• MOA: Increase NO causing vasodilation via cGMP.
• NO is produced frome arginine via NO synthases.

Two types of Angina based on Pathophysiology

Classical Angina(mc) Variant/Prinzmetal Angina

- Pain occur on : Exertion ,excitement, - Pain occur on : Rest
exercise emotion.
- Due to : Atherosclerosis. - due to : coronary vasospasm

- Nitrates,aspirin,beta blockers - Nitrates-coronary vasodilation.

Pathophysiology :

• Vessel is narrow and hence exertion or exercise cause increase in heart rate
and increase in Oxygen demand : More myocardial ischemia causes pain.
• Beta blocker decreases heart rate and decreases oxygen demand.
• If pain is releaved,last<10 min : Stable Angina.
• If pain is more than 15min and not relived and worsens : Unstable Angina
(Emergency-Bring to hospital MONA+ECG/biomarkers).

Screening test for CAD :

• Treadmill test ! increased HR !increased oxygen demand !if CAD present,
will precipitate Myocardial Ischemia.
• Drug stress test(dobutamine)!increased HR!increased oxygen demand.
If CAD present will precipitate myocardial Ischemia.
- This is known as Bruce Protocol.

ECG Changes DUKE SCORE

• ST depression >1mm in 2 or more leads for >80msec (>0.08sec)(>2boxes)
• TMT : if positive Duke score Indicate CAD present.
• Then we do Angiography for diagnosis to visualise vessels, blocks(number, site
and extent).
Treatment :
• Medical management : Aspirin, Clopidogrel,LMW heparin(enoxaparin)
Abciximab, beta blockers, Statins go correct dyslipidemia.
• Most effective treatment: Angioplasty or CABG in few cases Percutaneous
Intrvention : Dilate the stenosed vessel by balloon inßation and then place
stent.
- Stent : metallic/non metallic
- Drug electing stent -release drug and prevent re occulsion
 Coronary artery Bypass Grafting :
• Major surgery :Open heart surgery.
• We bypass the blocked vessel using graft.
• Best graft : Left internal Mamillary artery(LIMA) > Internal thoracic
artery(ITA) > Saphenous vein.

Indications for CABG :

• Triple vessel disease.
¥ Double vessel disease with signiÞcant LAD involvement Left main
Coronary Artery diseases.

Acute coronary Syndrome :

• Medical emergency.
• Pain >15min not releived and worsening(Cresendo pattern) Could be
MI or Unstable Angina.

Myocardial Ischemia
• Death of tissue due to ischemia.
¥ Causes coagulative necrosis and cause inßammation(worsened pain).
• Also as cell die,their contents leak out
• K+ Cause : ECG changes and Arrythmia Enzymes ,proteins-act as biomarkers
of MI.
• Treatment: Give MONA + ECG & check biomarkers.
M: Morphine - pain relief
O: Oxygen - relive hypoxia
N: Nitrates - IV nitroglycerine
A: Aspirin - Anti platelet(chewable)
Biomarkers :
• Ist to rise : Heart fatty acid binding protein(HFABP)within 30 minutes.
• 2nd to rise : Myoglobin (1-3hr)not speciÞc
¥ Maximum sensitivity and speciÞcity-rise in 3-8hrs
• Troponin-I > Troponin-T.
• Troponin-I is best for MI and re-infarction.
• Troponin-T stays longs-upto 14 days

LDH FLIP :
• Normal heart : LDH2>>LDH1.
• MI : LDH1>>LDH2 .
• Earlier even used CK-MB.
¥ ECG or biomarker conÞrms MI.
• If ECG or biomarkers are negative : UNSTABLE ANGINA.
• If ECG and biomarkers are negative,then it is unstable angina not MI.

ECG changes in MI

• Ist change: Tall T wave within mins of MI

• IInd Change: ST elevation within 1-3hrs (Tombstone appearances)
• IIIrd change:T wave inversion(12hours) biphasic
• IVth change : Pathological Q waves (24hours or more)or T wave
inversion.
• Persist all life, other S (ST&T)return to normal.

• Inferior MI - ST elevation in II,III,aVf(corresponding leads)

• ST depression in aVL (reciprocal leads).
• Treatment- PCI ( 90-120min) IV ßuids + Ionotropes.
• Nitroglycerine is Contraindicated.
Anterior wall MI :

Anterolateral wall MI :
 Inferior wall MI :

Management :
• Do ECG

1. STEMI :
• Give MONA
• Immediate PCI
• Door ti balloon time within 90 minutes upto 120mins.
• If not possible(patient far from hospital).
- Then thrombolysis can be done by injecting TPA(Tissue plasminogen
activator) : To break the Þbrin clot.
• TPA : • Streptokinase.
• Tenecteplase
• Acteplase
• Time for injecting=30 min upto 60min If no relief, do rescue PCI

2. NSTEMI :
¥ Give MONA(sufÞcient)
• No thrombolysis is given in NSTEMI and unstable angina
• Also Enoxaperin BD, Clopedogrel, Aboximab etc…
• Do delayed PCI if no relief.
SUMMARY
• Door to needle time=30 upto 60min
• Pain >15 minutes.
• ACS ! MONA Do ECG and biomarkers in case of unstable angina then
conÞrm.
• STEMI : Immediate PCI(TOC) within 90min-120min.Inject streptokinase
(needle time 30 min(60min) if all failed rescue PCI NSTEMI : no
thrombolysis should be done MONA+ Enoxaparin, beta blockers are
sufÞcient.
• Do delayed PCI in case of no relief
• DOC for NSTEMI : Heparin
 HEART FAILURE

• Ventricle: (RV or LV)

• Fail to pump blood, decreased SV decreased CO decreased BP Called as :
Cardiogenic shock (decreased tissue blood ßow).
• Also blood accumulate in vessel Called as : Congestion leads edema.

Types of Heart failure :

1. Systolic Heart Failure

• Pump failure
• Causes : - Myocardial Infarction.
- Myocarditis.
- Dilated Cardiomyopathy.
- Ventricular arrhythmia (V.Þb)
- Infections.

2. Diastolic Heart Failure

¥ less Þlling or Þlling failure
• Cause : - Restrictive cardiomyopathy.
- Constructive pericarditis.
- Cardiac Tamponade.
- Valvular lesion.
RIGHT HEART FAILURE
 • MCC : left heart failure
• Also pulmonary disease. COPD, Cor Pulmonale
• Valvular defect : - Pulmonary stenosis.
- Pulmonary regurgitation.
- Tricuspid stenosis
- Tricuspid regurgitation.
- Mitral stenosis.
- Mitral regurgitation.
- Inferior wall MI.
- Ventricular Þbrillation.
- Infection etc.

Pathophysiology :
¥ Low pulmonary blood ßow, poor exchange causes hypoxic hypoxia and
cyanosis.
• Blood accumulate in systemic vessels, systemic congestion.

Clinical Feature :
• Peripheral /Pedal edema : Pitting edema.
• Raised JVP >15cm H2O (distended neck veins).
• Chronic venous congestion.
• Hepatomegaly, Pulsatile liver(nutmeg liver).
¥ Ascites- shifting dullness on percussion and ßuid thrill.

Nutmeg liver
• Hepatojugular reßex : Press abdomen over lower area, Raised JVP due to shifting
of blood to right atria.

LEFT HEART FAILURE

Cause : - MI,V,Þb,Hypertension,cardiomyopathies,AS/AR(coarcation of Aorta) MS/MR.
HOCM,Inferior septic shock etcÉ

Pathophysiology :
• Less blood to body leads to cardiogenic shock, Low BP, Increased HR and
Decreased cardiac output

Clinical Feature :
• Coldand pale skin, Cardiogenic shock.
• Small Rapid pulse.
• Kidneys: Less blood ßow, decreased GFR, decreased urine output and
oliguria(<400ml/day) leads to Pre-renal failure.
In case of LVF :
• Weakness, Fatigue, Fainting etc…
• Dyspnea on Exertion, or breathlessness during activity.
• Limitation to physical activity.
• Cardiomegaly,gallop rythm in S3.
• Blood accumulate in pulmonary vessels causes pulmonary edema and
congestion.
• Increase load on RV-RVH, Pulmonary HTN and later RV failure.
• Pulmonary edema both sides congestion and failure occur Called as Congestive
heart failure.
• Pulmonary congestion cause increased pulmonary capillary wedge pressure
>25mmHg.
• Fluid leaks out into lungs (interstitium) cause Cardiogenic pulmonary
edema.
• Chest X-ray :
1. Bat wing Appearance.

2. Kerley B lines.
• Orthopnea present : Dyspnea on lying downas blood from legs shift to lungs.
• Patient sleep in propped up position.
• Nocturnal cough and paroxysmal nocturnal dyspnea.
• Patient wakes up with severe sudden breathlessness.
¥ Air amd ßuid in lungs create bubble sound and sputum(i.e they have inspiratory
crackles in base of lungs).
• Pink frothy sputum.
• Also inspiratory rate present and also pleural effusin present.

SUMMARY
¥ RHF- Raised JVP, Pedal edema, Hepatomegaly,Hepatojugular reßex.
• LHF: Cardiogenic shock, Pulmonary edema(S3), Orthopnea, PND.

CHF=LHF+RHF
• CHF Diagnosis by feature of both : Framingham

Framingham Criteria: 2 Major + 1 Minor.

 Compensated and uncompensated Heart Failure

• Compensated Heart Failure : Cardiac output and BP are maintained normal.

Very few sings and symptoms at rest.
• Uncompensated Heart Failure : Decreased cardiac output and decreased BP.
Cardiogenic shock and all features of CHF can be present: S3 sound PND,
Orthopnea etc…

Mechanism of compensation :
• Despite low Stroke volume, The Cardiac output and BP maintained by RAAS,
kidneys, Baroreceptors and increased sympathetic activity. Earliest Þnding of
compensated HF : Resting Tachycardia/ Palpitations also sweating known as
Diaphoresis.
• Patient complaints of night sweats.
• Also ventricular remodelling occurs in chronic HF.
• On physical activity, failing heart is unable to pump the required blood.

Limitation to Physical Activity and dyspnea on exertion :

On the Basis of New York Heart Association HF classiÞcation: 4 Types

• Class I,II,III :
• Comfortable at rest.
• Few or No signs and symptoms at rest : Compensated

• Class IV :
• Sign and Symptoms at rest.
• Bedridden
• not comfortable.
¥ classical Þnding of HF seen : uncompensated.
Investigation :
• Brain derived natriuretic Peptide levels : It is like atrial natriuretic peptide
they cause natriuresis they cause Na+ loss in urine leads to decrease volume
and congestion and decreased edema.
• NT Pro BNP levels used longer t1/2 BNP.
• X ray ECG-for MI or any other arrhythmia.
• Xray mainly for cardiomegaly, Pulmonary edema.
• Echo(IOC): Show all ,chamber, Valves, ßow, walls, EF.
• MUGA-(Multigated aquisition)
• Best for wall motion.

Treatment :
Goal is to decrease load(Burden).

¥ Increase efÞciency and pumping

• ACE inhibitors/ARBs -decrease sodium,and decrease volume
• Reduce preload by reducing the blood volume
• Prevent dynamic remodelling of ventricles hence, Best for Morbidity and
mortality and increase longevity of CHF.
• Diuretics- loop diuretics (furesamiden,torsemide) DOC acute pulmonary edema
• Vasodilators : Nitrates, CCB, decrease peripheral Resistance decrease afterload :
• it improve blood pumping.
• Beta blockers : decrease HR , less oxygen demand and decrease myocardial work
• Cavedilol(best) : Metoprolol, Bisoprolol : used in chronic compensated diastolic
• Heart failure.
• C/I -systolic HF/uncompensated HF/acute HF(poor pumping condition),because
beta blockers would reduce pumping.
• Ionotropes : use in systolic HF(decreased Ejection Fraction) to improve :
1. Cardiac glycosides : digoxin,digitoxin
- They inhibit sodium/potassium pump -increase contractility.
- S/E : digoxin is very toxic - need therapeutic monitoring, heart
block,arrythmia(MC),ventricular bigeminy, ST depression,
V-Wave etc.
• Most speciÞc : Non paroxysmal atrial tachycardia with AV block
• Antidote of digoxin : Digiband

2. Catecholamine : Epinephrine,Norepinephrine(nor adrenaline) :

Dobutamine : Increase Stroke volume via Beta-1 receptor.
Novadren : DOC for cardiogenic and neurogenic shock.
Heart failire with shock : nor adrenaline or dobutamine Milirinone-
inhibit PDE : It increases AMP, Increase Calcium and contractility.

3. New drugs (decreasing morbidity patient) :

• Omapatrilast and Saccubitril : Increase ANP and BNP.

4. Surgery :
• Ventricular assisting device:
- (Increases pumping incomplete failure)
- Final treatment option : Heart transplant.
 JUGULAR VENOUS PRESSURE !JVP"

• Internal Jugular Vein(0-8 cm H2O).

• JVP shows right atria changes Atria contract : a wave
• Ventricle contract : c wave
• Atria relax : x decent
¥ Atria Þlling :V wave Atria empty -y descend When TV open-y descend

Right Atria Contract = a-wave

RV Isovolumetric contractions = c-wave (push TV into RA).

Right Atria Relaxed = x-descent

Right Atria Fill by : VenaCava = V-wave

Right Atria Empty : When TV Open (RV Þll). = y-descent

c v

y
x
JVP in diseases :
• a-wave absent : Atrial Þbrillation.
• Big giant a wave : Tricuspid stenosis, Pulmonary stenosis.
• Canon a wave : double wave in AV dissociation(3rd degree AV block)
• Big V wave : due to Tricuspid Regurgitation more RA blood due to
regurgitation, Absent X decent and produce CV wave TR.
• Constrictive pericarditis : X and Y decent is Prominent.
• Cardiac tamponade : X prominent Y absent.
 CARDIAC TEMPONADE
• A medical Emergency.
¥ Massive Accumulation of ßuid around heart in pericardium.
¥ It compress and collapse the RV causing poor Þlling and
pumping If History of Trauma : RTA might bleed causing CT.

Clinical Feature :
BeckÕs Triad
1. Low blood pressure (hypotension).
2. Distension of the jugular veins.
3. mufßed or diminished heart sounds on cardiac auscultation.

Diagnosis :
• Check JVP changes : y-descent absent as RV cant Þll and RA.
• X wave prominent.
• ECG-QRS amplitude changes beat to beat(Axis shift called as electrical alterans).
• Pulses paradoxus- decreased BP in inspiration >10mmHg.
¥ ECHO shows ßuid in the pericardium and also shows compressed ventricle
 Pericardial effusion.

electrical alternans

Treatment :
¥ USG guided pericardiocentesis and ßuid removal.
¥ Pericardiotomy to drain out ßuid.
 CONSTRICTIVE PERICARDITIS

¥ Thick calciÞed pericardium prevent ventricular Þlling cause diastolic

dysfunction and failure.
¥ Mostly after pericarditis-Þbrosis and calciÞcation of pericardium.

Investigation :
• Pericardial Knock : Due to contracting ventricle and shrinking pericardium.
• Xray : Egg in cup appearance
• JVP-X and Y-wave both are prominent and Kussmaul sign positive: Increase
JVP on inspiration : absent in CT(cardiac tamponade) present in CP and
Restrictive CMP.

Treatment :
• Surgical management : Pericardectomy

SUMMARY
 HEART SOUND

• Auscultation : Valve areas MV,TV,PV,AV.

• Location : Intercostal space.
• 2nd ICS : AV(right) and PV(left) near sternal border.
• 3rd ICS : Erb’s point near sternal border(left).
• 4th ICS : TV(left) near sternal border.
• 5th ICA : MV in mid clavicular line(left) side also get apex beat.
1. S1 SOUND :
• 25-45Hz : Due to MV and TV closure at end of diastole and Start of systole
• If MV and TV are incompetant,they won’t close Blood regurgitate from
ventricle to atria called as mitral or tricuspid regurgitation in whole systole
There is murmur in entire systole called Pansystolic murmer
• Also MR/TR cause soft S1.

2. S2 SOUND :
• Closure of AV/PV at end of systole and start of diastole.
• If Av/PV wont close in diastole, the blood can regurgitate from aorta LV in
Early diastole
• If AV/PV are incompetent,the aorta recoil and send blood back to LV,
Immediately in diastole. Hence AR/PR cause early Diastolic Murmur.

¥ Also in AR/PR, soft or mufßed S2.

• S2 is due to closure of AV and PV
• S2- A2P2[A2 appear before P2 as aortic pressure is higher].
• Physiologically splitting in inspiration :
1. Gap between A2 and P2 Paradoxical/Reverse splitting : P2 —A2.
- Seen in LBBB and aortic stenosis.
2. A2 Delayed Wide splitting : A2P2 gap more.
- Seen in RBBB ,Pulmonary HTN, Pulmonary stenosis
• Fixed split : Gap is same in Inspiration and expiration
- Seen in ASD
• Variable split- Change with inspiration and expiration.
- Seen in VSD and MR.

¥ Mitral valve and tricuspid valve open for ventricular Þlling mainly in middle
of the diastole.
• Mitral stenosis and tricuspid stenosis : Narrow opening of mitral and
tricuspid valve.
¥ Poor turbulent ßow in diastole.
 • Opening of MV/TV : Opening Snap(OS) and mid diastolic murmur.
• AV/PV : Open in systole.
• For ejection : Maximum in the middle of systole.
• AS/PS : Mid systolic murmur and ejection murmur.
• When AV/PV Open in AS/PS they produce Ejection click.

3. S3 SOUND :
¥ Due to early ventricular Þlling when MV and TV open.
• Physiologically S3 heard in : Athlete(LVH), Pregnancy, Middle/old
age because of Hard LV walls.
• Pathologically S3 heard in : Cardiomegaly, LHF,(S3 gallop).
4. S4 SOUND :

¥ Due to late ventricular Þlling, Appear just before S1.

• Physiologically : notaudible as freguency is <20Hz.
• Pathologically : S4 very high in diastolic HF, Hypertrophy Aslo in PSA, Pre
systolic attenuation in MS.

SUMMARY

• Mitral regurgitation and tricuspid regurgitation -Pan systolic murmur+soft

S1+variable shift S2
• Mitral stenosis and tricuspid stenosis-Opening snap +mid diastolic murmur
• Atrial stenosis and pulmonary stenosis-Ejection click+MSM
• Atrial regurgitation and pulmonary regurgitation-End diastolic murmur/Mid
diastolic murmur+ Soft S2.

E. Click Opening snap

S1 S2 S3 S4

Systole Diastole

S3 : Ventricular Gallop Rhythm.

S4 : Atrial Gallop Rhythm/Atrial kick.

VALVULAR LESION

• IOC : ECHO.

Cause :
• Congenital : since birth
• Old Age : Degenerative changes.
• Children/India : Infections (MC : RF/RHD)

Treatment :
• Mostly asymptomatic
• If symptomatic : Valvuloplasty.
• This produce classical sign of AR :
• Water hammer or collapsing pulse.
• Dancing carotides Called as : Corrigan sign.
• Noding of head with heart beat= Demusset sign.
• Cappillary pulsation:Nail bed: Quinckes sign.
• Uvula pulsation: Muller sign.
• Traube sign : Pistol shots over femoral artery.
• High BP difference b/w upper sl lower limb is called as : Mills sign.

On Examination :
• Pulse pressure , high SBP but low DBP soft S2, EDM or MDM Called as
Austein ßint murmur.
• Herat beat at Erbs point and patient is sitting and learning forward

Investigation :
• X-ray, ECG, ECMO
• pulmonary congestion and oedema , RVM, pulmonary hypertension are seen.

Treatment :
• Treatment of CMF Treat to Inotropes, ACE-I, ARB’S
Surgery! valvuloplasty/ valve replacement.
 MITRAL REGURGITATION

• M/C cause : RF / RHD ( India ).

• Other causes : congenital Infective endocarditis.
• MVP( mitral valve prolapse) : MC valvular lision (worldwide)

Pathogenesis :
• MV cant close in systole so left venticle causes regurgitation in to left artria
• Left ventricle causes: Pulmonary oedema congestion.
• Cardiogenic shock a/t less blood to aorta !Acute MR simila to CMF
• The blood entering left ventricle cause Eccentric hypertrophy.
• Finding soft S1, Pan systolic murmur:
- This murmur heard best in standing as gravity will pull mitral valve down
causing more regurgitation.
- Loud S3 due to hypertrophy.
- Apex beat shifted laterally due to LVH.
- Pulmonary HTN, loud P2, PVM , Left atria Enlargement: A Þbrillation.
- ECG,X-Ray,ECHO-LVH, atrial enlargement.

Clinical feature :

• Young females with acute panic attack feel like dying, Palpitation,
Sweating.

Treatment :

• Treat the pulmonary congestion/HF/A.Fib, Valvuloplasty/Replacement

• Mitral Valve Prolapse- Mitral Valve Prolapse d/t myxematous
degenartion ,damage to chordae tendinae or papillary muscle.
 Rheumatic Fever and Rheumatic Heart Disease

• First,there is pharyngeal infection/sore throat caused by Group A streptococcus-

High ASO titre(Anti streptokysin O)
• Antibodies formed against M protein of streptococcus cross reacts with bidy tissue
and damage them.Eg-joints,heart,skin,etc
• Type II HSV
• Female >Male age group affected (5-15yrs)
• Primary attack rate-3-5%
• Secondary attack rate-15-50%
• Hence,prophylaxis are given to prevent another infection causing severe damage.

Diagnosis :
Revised Jones Criteria (2 major+1minor).
5 Major :
1. Sydenham chorea(dance)
2. Migratory polyarthritis(mc)
3. Carditis
4. Erythema marginatim(least common) Subcutaneous nodules: Near
joints,bones

Minor :
1. Fever
2. Increased PR interval >0.20second.
3. Increased CRP(Marker of acute inßammation).
4. Increased ESR.
5. Arthralgia (Joint pain).
 Acute Rheumatic Fever
¥ Ist Mitral regurgitation occur, later there is healing and calciÞcation causing
Mitral stenosis.
• MC valve lesion in RF/RHD.
• Murmur : Carey Coomb’s murmur

Pathophysiology :

• Rheumatic Granuloma/Aschoff Bodies.

¥ Fibrinoid necrosis due to collagen Þbre deposition, WBC, RBC
called as Caterpillar Cells/ Antishkow cells (Actually macrophages).

Aschoff Bodies
 • Also, vegetations along line of closure in valves and McCullum patches.

Treatment :

• DOC-Benzathine penicillin(IM) 1.2million unit or oral penicillin V-250mg 2times

a day
• Also add steroid
• Note : if allergic to penicillin give sulfa drugs Eg: sulfonamides

Prophylaxis :
• Benzathine Penicillin(IM)given.
• Every 4 weeks to 21years.
• If no cardiac lesion : for 5 years after attack till 21yrs.
• If residual cardiac lesion : for 10yrs after attack till 40yrs.
• Always the higher one should be chosen.
 INFECTIVE MONOCARDITIS

• MCC of Acute IE : Satph Aureus (overall mc), Coagulase +ve

• Native(natural)valve.
• IV drug user : Right side IE :- Staph Aureus and Enterococcus.
• ProstheticValve : Causative agent :- Staph Epidermidis (Coagulase -ve).
• for subacute IE : causative agent :- Streptococcus.

Diagnosis :

¥ ModiÞed DukeÕs Criteria

Main Finding :

1. Janeway lesion in Palm (Painless).

2. Osler node on Þngertips (Painful).
3. Splinter haemorrhage (Nail).
4. Roths spot (Retinal haemorrhage).
Treatment :

• IV antibiotics based on sensitivity

• If MRSA(Methicillin resistant Staph aureus)
- DOC : Vancomycin
- S/E -Redman d/t histamine syndrome
• If VRSA(Vancomycin resistant Staph aureus)
- DOC : Daptomycin
• If lung infection : don’t give Daptomycin as it is broken by surfactant.
So use : linezoid.
 HYPERTENSION

• Silent Killer : Few or no signs and symptoms

- Eg : Headache, Sleep disturbances, Polyuria due to pressure diuresis and
Irritability

Malar ßush

• Ice berg phenomena : Few patients can be detected and out of that few are
Treated (Rule of Half).
• Prevalence : 29.8% approx 40cr
• M>F, after menopaise females have similar prevelance of hypertension.
• BP Estimation : Best and most accurate is intraarterial BP recording but
Invasive method, so used less, Used in ICU.
• Most commonly used : Sphygmomanometer

Sphygmomanometer
Sphygmomanometer

• Cuff at Heart level.

• Cuff length : 2/3rd of mid arm circumference (MAC).
• Cuff Width : 1/3rd of mid arm circumference (MAC).
• Adult cuff size :

• In clinical: At least 2 recordings, 5 minute apart. Patient is well rest and calm.
• Best : 24 hour Ambulatory BP recording.
• White coat Hypertension : BP increases on seeing a doctor/hospital.

Diagnostic criteria for Hypertension :

• JNC-8 SBP "140mmHg DBP "90mmHg

But now in INDIA , AHA guidelines also followed :

• HTN : >130/80mmHg (go for 140/90 in exam if not given)

• Normal : <120/80mmHg.
• Pre HTN : SBP 120-129mmHg , DBP 80mmHg.
• Hypertensive Crisis : >180/120mmHg.
• If either SNP or DBP high then known as Isolated Systolic or diastolic HTN.

Types of Hypertension

1. Primary Hypertension

• Also known as Essential Hypertension(95%).

• Mostly idiopathic.
• Mostly environmentak/genetic factor.
2. Secondary Hypertension
• High BP due to some disease.
• MC Renovascular causes : Renal artery stenosis(increased Renin increases
BP via RAAS).
• In these cases ACE Inhibitors and ARBs are absolute contraindication.
• Also glomerulonephritis Eg: Nephritic syndrome(PSG, IgA Nephropathy).
• Poly Cystic Kidney Disease.
• Endocrine : Pheochromocytoma, Conn’s syndrome, cushing Acromegaly,
hypothyroidism etc.
• Others : SLE, Pregnancy, Pre-eclampsia, MI, COA, PAN, Obeisity,
Scleroderma, PCOD.

Complication :
• Arteriosclerosis : Hardening of vessels.
• LV hypertrophy and failure.
• Malignant nephro-sclerosis.
• Flea beaten kidney.
• Hypertensive Retinopathy : Salu sign, gunn sign, bonnet sign Copper
and silver wiring.
• Artery Venous crossing Haemorrhage : Stroke,hypertensive bleed.
- Mc site : Putamen
Treatment :
• Weight Reduction : Most effective can reduce BP 15-20mmHg
• Life style modiÞcation : avoid stress, Meditation, Exercise, Stop smoking and
Stop alcohol.
• Dietary approach to stop HTN : Can reduce BP by 8-14mmHg.
• Decrease salt intake : <2-3gm/day.
• If >50 yrs ,Diabetic and Hypertensive : <1.5gm/day Reduce saturated fats,red
meat,cholesterol rich foods Correct dyslipidemia.
• Medical treatment : >140/90mmHg.
- First line Drug : ACD
1. ACE Inhibitors.
2. CCB : Calcium channel blockers.
3. D-Diuretics : thiazides

Young (<55-60yrs) or DM Old(>60yr).

 HYPERTENSIVE CRISIS

• BP >180/120mmHg.

Hypertensive Urgency Hypertensive Emergency

• No signs & symptoms • Signs & symptoms present.

• No end organ involved. • End organ involvement
• Rx-In OPD. • Rx-In hospital bring BP to normal in 1hr.
• Bring BP to normal in 24-28hrs. (If pheochromocytoma, Pre-eclampsia and
dissection of aorta).
• Others : Decrease BP by 25% in Ist hour
and then reduce to normal in 24-48hr

• Rx in Pre eclampsia : IV Labetolol(Alpha1 and Beta1 blockers)

• Rx in Pheochromocytoma : IV Labetolol,phentolamine(alpha1blocker)
• Rx in dissection of aorta : B(Esmolo)+C(CCB)Nicardipine
• Rx in MI : Beta + CCB To decrease BP if HTN present.
• Rx in Cerebrovascular disorder : Labetolol + CCB(Nimodipine,Nicardipine).
• Rx in renal disease-Fenoldopam(dopamine agonist).
• Rx in pulmonary edema : Systolic dysfunction or diastolic dysfunction.

- Avoid Beta blocker : Use CCB and loop diuretics and NTG.
- Use Beta blockers with loop diuretics, NTG.
 SHOCK

¥ Reduced tissue blood ßow

• If BP is Low<90\60 : Uncompensated shock.
• If BP is normal then : Compensated shock

Types of shock

1. Hypovolemic shock

¥ Loss of blood/ßuids.
• Low BP volume,Low cardiac output, low JVP/CVP.
• Cold shock : Oliguria,muscle weakness etc.
¥ Rx-IV ßuids/blood.
• Urine output monitoring for treatment and prognosis.
• If oliguria persist,give dopamine(increase urine output).

2. Cardiogenic shock
• Due to Heart failure,less cardiac output and BP,decreased urine,cold shock etc..
but increased JVP ,increased CVP and Þndings of CHF: S3, edema,PND.
• Rx : DOC- Noradrenaline/dobutamine also treat CHF.
 Distributive or Warm Shock

Pathophysiology :
• Vasodilatiin causing the blood to accumulate in vessels mainly veins and less
return to heart lead to decreased cardiac output and low BP.
• Body is warm because blood is still present in body.
• Rx : Vasoconstriction.

Types of warm shock

1. Anaphylactic shock
¥ Due to allergens like insects, bee sting Food -MC sea food(shell Þsh) peanuts
• Histamine cause vasodilation, decrease BP, Rashes, itching Bronchoconstriction
(Via H1 receptors)swelling of eyelid ,lips, face, Angioneurotic edema.
• Rx : DOC - Adrenaline (alpha-1causes vasoconstriction, Bronchodilation).
Subcutaneous or IM 1:1000 ratio or 0.5ml

2. Neurogenic shock

• loss of sympathetic activity Causing vasodilation.

• Eg : H/O spinal injury, Anaesthetic drug.
• Rx : DOC : Noradrenaline,phenylephrine(alpha1 vasoconstrictor)

3. Septic shock

• Cardiogenic + Distributive
• Bacterial endotoxin-Inhibits myocaedium and vasodilation.
• Shock with fever,BP,low BP
• DOC: IV antibiotics and noradrenaline
4. Vagal shock

• Vagus inhibit heart by : M2 receptor.

• Low BP, Low HR(d/t cold water,drowning fear).
• DOC : Atropine.

• Shock Index=HR/SBP
• Normal =0.5-0.7
• Shock !1 Hemodynamically unstable
 CARDIOMYOPATHY

• Abnormal muscle structure/proteins

3 types :
1. Dilated CMP (MC).
2. Restrictive CMP.
3. Hypertensive Obstructive Cardiomyopathy.

1. DILATED CARDIOMYOPATHY
• Systolic dysfunction
• There is damage to myocardium,can’t pump blood chamber is called dilated which
resembles CHF(Systemic heart failure).
• Investigation & Treatment : Same as CHF.

MC Cause :
• Viral infections than alcohol
• Also drugs like Doxonibion
• Pheochromocytoma
¥ Vitamin B1deÞciency : Beri beri etcÉ

2. RESTRICTIVE CARDIOMYOPATHY

¥ Diastolic dysfunction,similar to Constrictive Pericarditis Poor Þlling,Kussmaul

positive.
• Rx : Beta blocker, Correct the cause.
• Causes : InÞltration by amyloid deposition.
Glycogen storage disease.
3. HYPERTENSIVE CARDIOMYOPATHY

• Autosomal Dominant(most dangerous)

• Sudden death is young/athlete.
• Mutation in Chr.14:gene for myosin heavy chain.
Pathophysiology :
• Intra ventricular septum hypertrophy which causes sub aortic obstruction
• Similar to aortic stenosis
• Pluses bisfriens(double peak)
• ECHO : LVH, Septal hypertrophy, Banana shaped ventricle.
• Rx : Myomectomy of septum/Ablation of septum by alcohol,heart transplant.
• No drugs, All drugs are C/I except Beta blockers
4 RESPIRATORY SYSTEM

• Lungs add O2 and remove CO2 from blood.

• Hypoxia : Tissue fail to utilize O2

4 Types hypoxia :

1. Hypoxic hypoxia : lungs to oxygenated blood.

Ex : lung diseases high altitude asphyxia.
Hallmark : PaO2 decreases : < 60mmHg and spO2 decreases : <94%.

2. Anemic hypoxia : less Hb to carry O2 to tissue.

Normal PaO2 and no cyanosis.
Patient look pale.

3. Stagnant/Ischemic hypoxia : Blood ßow of tissue is poor.

Ex : Shock, HF, vascular disease
Normal PaO2 and Sever cyanosis.

4. Histotoxic hypoxia : Despite negative blood O2 tissue fail utilize O2.

Ex : Cyanide : inhibit complex : 4 of ETC.
Co-poisoning - also inhibit complex-4 but copoisoning is mainly, Anemic
hypoxia : No cyanosis and negative PaO2.

SUMMARY
• PaO2 only in hypoxic hypoxia.
• Negative PaO2 in all others hypoxia
• Cyanosis : Bluish discolouration of skin and mucus membrane d/t Increase in reduce
Hb >5g% or SPO2 <75%.
• Absent in anemia as low Hb and Histotoxic Hypoxia as tissue dont use O2, Hb is
Þlled with O2.

Cyanosis
• Central : Seen on face lips Lung disease
• Peripheral : seen in :-
- Þngers hand feet
- Cardiovascular disease
- Ex : Shock raynauds disease cold water

Peripheral Cyanosis Central Cyanosis

Raynaud’s disease
W : White pallor d/t Vasoconstriction.
B : Blue cyanosis/decreased O2.
C : Congestion Redness.

White Blue Red

 • DOC : CCB
• Treatment : Avoid exposure to cold, Caffeine and Stop smoking.
• Clubbing : Indicate chronic pulmonary or cardiovascular disease.

• Hypoxia cause increased VGEF(vascular endothelial growth factor). & PDGF

(platelet derived GF).
- They cause tissue growth & proliferation at Þngers : drumstick/clubbing Þnger.
• Earliest sign : Schmaroth sign : distorted angle of nail bed.

2 main process in Lungs : and Diffusion

1. Ventilation :

• It is amount of air going in & out for expense per minute. It is given by TV & RR or
both.
• Fall in PO2 in alveoli & blood cause hypoxic hypoxia. Also cant be expired out CO2
of poor breathing : PaCO2
Example :
1. RLD(Restrictive lung disease).
2. Severe obstruction : Foreign body, Tumors, COPD, Asphyxia, Choking.
3. Neuromuscular disease : GBS, Myasthenia Gravis, Diaphragmatic Paralysis
(Phrenic nerve).
4. Respiratory depression : Opioids(morphine), alcohol.
5. Chest wall injury : ßial chest, Tension pneumothorax.
2. Diffusion
• Movement of O2 from alveoli to blood in pulmonary capillaries.
• Diffusion disorder are mainly membrane defect : Decreased area or Increased
thickness
• Low PaO2 despite normal PaO2 Increased(A-a)gradient, hypoxic hypoxia.
Example-Pneumonia,Covid-19,ARDS,interstitial lung disease.
• Occupational lung disease : Sarcoidosis, Asbestosis, Silicosis, Bassosis.
• IOC for diffusion D : DLCO(Diffusion Capacity in lungs for CO
normal 100% diffusion).
- Low DLCO : Inmembrane diffusion disease&anemia due to less Hb to bind CO.
- Increased DLCO : Athletes, High Altitude dweller, Asthma, Polycythemia
 Respiratory Failure

• Lungs fails to oxygenate blood.

• 2 Main Types.

• Type-I respiratory failure will become Type-II once respiratory muscle are
fatigued.

Ex : Emphysema : Initially type-I later Type-II

Covid 19.
• Respiratory failure Type III : Iatrogenic
• MC : Intra/post operative patient Patient can have collapse/
damage to alveoli(atelectasis).

• Respiratory Failure Type IV- Variant of type-II.

• Ischemia & fatigue of respiratory muscles.

• Eg : Shock,HF.

Two types of Lung Diseases

RESTRICTIVE LUNG DISEASE CAN BE TWO TYPES

 OBSTRUCTIVE LUNG DISEASE
#
BETA2 Agonist test(bronchodilators)

Good Response : Poor Response :

• Decreased wheezing known as • Irreversible obstruction

reversible obstruction.
• Asthma. • COPD,COLD
• In COPD :
- Blue bloaters : indicate Chronic bronchitis.
- Pink puffer : indicate emphysema.
 ASTHMA

• Reversible intra thoracic obstruction

• Type 1 hypersensitivity(allergic reaction) Hyperresponsive airways with
hypertrophy of smooth muscle.
• Trigger/ Antigen like : Pollen, Dust, Aerosols.
#
• Bind IgE on mast cells
Histamine&leukotrine(LTC4,D4,E4) from mast cell & eosinophils (IL-5).

• Bronchoconstriction : Episode of wheezing, breathlessness(dyspnea), chest

tightness.

Histopathological examination :
¥ Airway inßammation,inÞltration to eosinophil : Mucosal edema, Hypertrophy
of muscle.
• Three main Þndings :
1. Charcot Leyden Crystals.
2. Cruschmann spirals.
3. Creola bodies.

Charcot Leyden Crystals. Cruschmann spirals.

 Creola bodies.

2 Types of Asthma

Intrinsic Asthma Extrinsic Asthma

• Non allergic. • Allergic.

• Occurs late in adults. • seen in early life,children.
• H/O Respiratory infection. • Type I HS.
• Trigger : cold air,exercise,drugs. • Trigger : Allergen.

Clinical features :
• Seasonal variations : Spring season.
• Recurrent attacks of wheezing, Dyspnea, Cough.
• Poor exercise tolerance.
• Early fatiguabiloty,chest tightness,suffocation
• Tripod position
• Exertion worsens the condition-so advised to slow and
deep breathing.

Tripod position
Investigation :

• Spirometry(PFT)
• Normal VC, low FEV1%,high RV & high FRC due to Air trapping.
• Mostly type-I respiratory failure due to hyperventilation and respiratory
alkalosis.
• Severity on the basis of FEV1%
- Mild : <80-50%.
- Moderate : <50-30%.
- Severe : <30%.

¥ Also there is morning/evening variation in air ßow. So, measure PEFR

(peak expiratory ßow rate).

• Normal=250-500L/min
• Self monitoring device.

ClassiÞcation based on frequency of attacks :

1. Intermittent asthma : <2days in a week or <2 nights in a month or once a week.

2. Persistent Asthma : 3 or more attack.
• Mild : 3-6 day a week.
• Moderate : Daily.
• Severe : Multiple attack in a day.

Treatment :
• Avoid exposure
• Patch test to identify allergens

Patch Test
Prophylaxis : Before attack to prevent it.

1. Monoclonal antibody : Agonist

- IgE : Omalizumab
- IL-5 : Mepolizumab & Reslizumab.

2. Mast cell stabilizers :

- Sodium Cromoglycate.
- Nedocromil sodium.
3. Leukotrine receptor antagonist :

- Montelukast.
- ZaÞrleukast.
4. Lipooxygenase inhibitors :
- Zilwuton
5. Anti histamine :
- Cetrizine.
- Levocetrizine.
- Ketotifen

Controller’s
¥ Steroids(DOC) : For persistant because it decreases inßammation and would
reduce attacks.

Steroids are 3 types :

1. Inhalational corticosteroids : Mild to moderate.

2. Oral corticosteroids : Severe.
3. IV-corticosteroids : status asthmaticus.
Inhalation corticosteroids :
¥ Budenoside, ßuticasone
• Less risk of cushing syndrome,as they act locally.
• Side effect-oral candidiasis (DOC : Clotrimazole)
• Prevented by rinsing mouth after use.

Relivers are bronchodilators :

• used in attacks.
1. Muscaranic antagonist :
• inhibit M3 Receptor.
• Eg : Ipratropium bromide, Tiotropium bromide
(COPD, status asthmaticus).

2. Beta 2 agonist :
• bronchodilator
• Eg : - SABA : Salbutamol,Terbutaline.
- LABA : Salmeterol,formeterol,arfometerol(fastest).

• Start with SABA# LABA#LABA+ICS. (Intermittently SABA can be used)

Management as per GINA 2019 guidelines

• For attack reliever : SABA!If not relived LABA+ICS.
• Persistent : Mild,use controller.If attack,use reliver.
• Moderate : Use controller, Low dose ICS,if not controlled use medium/high
dose ICS, still not controlled, ICS+LAMA/LABA/LTRA or
MAB,!OCS(severe).
 STATUS ASTHMATICUS
• Minimum breathig, Minimum chest movement.
• Silent chest(no breath sounds).
• Nebulisation : make drug into vapours
¥ 100% humidiÞed O2. Salbutamol
• IV hydricortisone. Ipratropium by nebulization.
• IV theophylline.
• SC terbutaline
• Brittle’s asthma:poor response to treatment & high PEFR variability(>40%).
• Rx : Adrenaline(SC/IM)IV steroids.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

• Cigarette smoking
¥ Chronic inßammation and obstruction
• Cough with sputum.
¥ COPD is classiÞed into chronic bronchitis and emphysema.
• Chronic bronchitis.
• Airway affected more.
• H/ O smoking/pollution.

Diagnostic criteria :
• Productive cough with copious sputum for >3months or for "2consecutive
years.
Pathophysiology :
SMOKING

Damage epithelium " Mucus Production.

#
Cause metaplasia/neoplasia. "
Goblet cell
#
Change in columnar epithelium " Mucosal gland
to squamous cell carcinoma. (Hyperplasia).

• Damage to cilia cause

poor mucociliary
clearance : mucus stasis
and hence cough with
sputum & respiratory
infection.

¥ Muosal edema,inßammation,thickened smooth muscle,increased mucus,

Poor mucociliary clearance [irreversible airway obstruction &high
infection].
 Histopathological examination
• Reid index normal : 0.4 or less. (40%).
• RI=mucosal gland/wall thickness
• Chronic bronchitis : high reid index 0.5 or more.

Clinical features :
• Productive cough >3months with copious sputum.
• Cyanosis(central)
• Clubbing
• Respiratory infection
• Wheezing, Ronchi (wet sound due to secretions).
• Dyspnea, Tripod position,chest tightness,suffocation.
• Age 40-55 years to obese .
• Type II respiratory failure : Blue Bloater.

Investigation :

PFT # " FEV1% : <80%.

RV and FRC due to Air trapping.
Normal Recoil and normal Compliance and normal DLCO.

X-ray : Broncho Vascular markings.

Treatment :
• Quit smoking : Nicotin gum/patch.
• DOC : Varenicline
LANA/LAMA & Steroids.
• Antibiotics if infection present.
• Mucolytics : bromhexine, Ambroxol, N-acetyl cysteine.

EMPHYSEMA
Pathophysiology :
• Acquired by smoking/pollution
• Congenital by genetic disease.
- Defect in Serpine-1 gene Chr.14
¥ Alpha-1 antitrypsin deÞciency.
• Lungs have compliance and recoil due to elastic protein known as Elastin.
• Elastin is broken down by elastase enzyme from neutrophils.

• So alpha anti trypsin,(tissue inhibitor of metalloproteinase)

TIMP,Prevent elastin breakdown.

Smoking Alpha 1 antitrypsin

Neutrophil
Elastase

Break elastins

Lead to : • Poor expiration cause air trapping.

• Chest tightness,suffocation.
• Decrease Recoil and Increase Compliance.
Dilated acinus :
• Respiratory bronchiole in all alveoli.

1. CENTRIACINAR :
• Clinically MC due to smoking.

2. PANACINAR
• Entire acini involved.
¥ alpha-1 antitrypsin deÞciency.
 The dilated acinus also produce subpleural bulbs/bulla.
#
Ruptures leak air into pleural
#
Known as closed Pneumothorax.

BULLOUS EMPHYSEMA BARREL CHEST

¥ Hyperinßated lungs & barrel chest increased: Antero-Posterior diameter.

¥ Just like chronic bronchitis : Airway inßammation, mucus increases,edema,poor
mucociliary clearance:
- Irreversible obstruction.
- Less cough and less sputum in emphysema.

• Destruction of acinus and pulmonary capillaries causes poor oxygen

diffusion,decreased DLCO. Emphysema only obstructive lung disease with
diffusion defect.This cause hypoxic hypoxia despite hyperinßated lungs.Also
increased RBC count to correct hypoxia.
• Patient hyperventilate-pressed lip breathing,pink puffer,high v/o
mismatch,respiratory alkalosis Respiratory failure type I initially,then
advances to type II due to overinßated lungs(poor breathing)
Clinical features of emphysema :
• Age 50-70years
• Thin and pink puffer
• Barrel chest
• Less cough&less sputum
• less respiratory infections Wheezing,dyspnea,lip breathing.
• Tripod position,
• cor-pulmonale(less than chronic bronchitis)
• Effort intolerance.
On examination :

• Percussion : high response and low heart sound (because of hyper-inßated lungs).
• Xray : hyper-lucency(dark).
¥ Hyperinßated lungs.
¥ Low lying ßat diaphragm
• Tubular vertical heart.
• PFT : Low FEV1%, decreased VC,Increased RV & increased FRC (air trapping)
Low MEFR.
• Increased Compliance & recoil, decreased DLCO, increased V/O ratio.

Severity by FEV1% called Gold Criteria :

• Grade I : " 80%

• Grade II : <80-50%
• Grade III : <50-30%
• Grade IV : <30%.
Treatment :
• Similar to chronic bronchitis
• MMRC & CAT score for severity COPD assisted test.
• LAMA/LABA with steroids
• Mucolytics
• Antibiotics
• Most importantly : stop smoking.
• Surgery : If severe dyspnea : Bullectomy, Lobectomy, Pneumecyomy.
• Last stage : Lung transplant based on BODE INDEX.
• BMI, Obesity, Dyspnea, Exercise Capacity.
 BRONCHIECTASIS
• Irreversible airway obstruction and dilatation(ectasia).
• It is mostly seen after infection,airway obstruction by foreign body,tumors etc.
- There is destruction of airway,cilia,increased mucus,poor mucociliary
Clearance, recurrent respiratory infection.There is Airway dilation.
• Similar to chronic bronchitis,but to airway dilation and not associated with
smoking.
• MCC in India : TB.
• MCC in developed countries : Cystic Þbrosis.
• Also seen in Katargener syndrome.

Katargener syndrome
• Defect in axonemal dynein(molecular motor).
• Helps in ciliary movements.
Clinical features : infertility,immotile sperms, situs inversus.
Eg : heart on right side known as Dextrocardia.
• Treatment : Mucolytic, Antibiotic.

Clinical features of bronchiectasis :

• Productive cough with mucopurulent sputum.
• Recurrent respiratory infections(fever,cough).
• Hemoptysis can be seen.
• Cyanosis,clubbing.
• Dyspnea,wheezing.
Investigation :
• Decreased FEV1% similar to chronic bronchitis.
• TB sputum Culture, Xray, CB-NAAT.
• Xray and CT(HRCT)best
• Signet ring & Tram track appearance in CT.

(A) A chest X-ray shows bilateral tram lines representing thickened

bronchial walls.
(B) Chest computed tomography shows diffuse bilateral bronchial wall
thickening and bronchiectasis.
 PNEUMONIA
¥ Inßammation of lung parenchyma.

ClassiÞed into 3 :

1. Hospital Acquired Pneumonia : Occurs after 48-72 hours of admission.

2. Community acquired pneumonia : before hospital admission.Before 48hrs
after admission
3. Ventilator Associated Pneumonia : after 48-72hrs of intubation.
• MC : Klebsiella.
¥ Most SpeciÞc : Actinobacter.
• If drug resistant : Pseudomonas.

Bacterial Pneumonia :
• CAP (Community Acquired Pneumonia).
MC : Streptococcus inßuenzas,
H. inßuenzae
Moraxiella.

• HAP (Hospital Acquired Pneumonia). Drug resistance

1. Multi-drug resistance :
• MC : Pseudomonas.
• MRSA.

2. Non multi drug resistant :

• Streptococcus Pneumoniae.
¥ H.inßuenzae
• Mycoplasma.
• Staph aureus.
Viral Pneumonia :
¥ Inßuenza (bird ßu,swine ßu).
• Covid-19
• Adenovirus,rhinovirus etc…

1. Exposure to birds and peguons : by Chlamydia Psittacosis.

DOC : Azithromycin.

2. Hotel/AC ventilation/cruise ship : Legionella Pneumoniae or Legionnaire disease.

DOC : Rifampicin + Azithromycin.

3. HIV infection : MC S.Pneumoniae.

- But Opportunistic infection is by : Pneumocystis jerovici/Carnii(Giemsa stain).
DOC : Cotrimoxazole.

4. Sheep goat exposure : Coxiella burnetti

DOC : Doxycycline + hydroxy chloroquine.

5. Alcoholics : Aspiration vomitus

MC : S.Pneumoniae.

6. Red currant jelly sputum : Klebsiella, Friedlander’s pneumonia

7. Atypical pneumonia : Viruses and mycoplasma.

DOC : Erythromycin/Doxycycline.

Clinical features of Pneumonia :

• High grade fever with chills & rigors.
• Severe dyspnea and increased respiratory rate.
• Cough with greyish purulent sputum.
• Hemoptysis.
• Chest pain due to pleural involvement.
 On examination :
• Consolidation : Dull percussion.
• Increased vocal fremitus,decreased chest expansion.
• Bronchial breathing is hesrd-loud,high pitch.
• Expiration longer than inspiration.
• Coarse crepitations.

Three types of Pneumonia :

Lobar Broncho Interstitial

Site • Alveoli,whole lobe. • Area near bronchi. • Interstitum

• Dense consolidation • B/L patchy opacity. • B/L diffuse opacities

Xray of entite lobe(U/L). known as ground glass
opacities.
• Klebsiella, • S. aureus • Viruses.
Organism • S. pneumoniae • Chlamydia • Mycoplasma.
• Legionella ¥ H.inßuenza • P.jerovici.
Atypical Pneumonia :
• Low grade fever,
• less clinical features,
¥ less Þndings, lymphocytes,
• less cough & less sputum.

Typical Pneumonia :
• Mostly viruses,
• high grade fever,
• more clinical feratures,rapid onset.
• more cough & more sputum.

Stages of lobar pneumonia :

1. Congestion : 24-48hrs
- Increased vascularity & increased RBC,WBC in blood.
2. Consolidation : lung look like liver, hepatization.
- Red Hepatization : 2-4days. RBC in alveoli
- Grey Hepatization : 5-8days. After infection RBC degraded, WBC
(neutrophils,macrophages), Þbrinosuppurative exudate.
3. Resolution : 8-10days.
- Clearing of alveoli from dead cells & inßammatory debris is removed
Alveolar architecture restored,healing by Þbrosis.
Investigations :
• Xray, HRCT, Sputum(culture and microscopy).
• RT-PCR for covid-19,
• Viruses, Antigen test.
• CBC, ABG, SpO2.

Management :
CURB-65 SCORE
• C : Confusion
• U : Uremia(BUN >20mg% or >7mmol/l).
• R : Respiratory rate increased(>30/min)
• B : BP <90/60mmHg :shock.
• 65 : Age >65yrs.

• Each parameter score =1 so, Total=5.

• 0-1 = OPD treatment with antibiotics.
• 2-3 = Admit patient with IV antibiotics.
• 4-5 = ICU.
Antibiotics
• Macrolides, Penicillin(Amoxiclav).
• Fluroquinolones
¥ Doxycycline (Oßoxacin, Levoßoxacin).
• IF MRSA : VANCOMYCIN.
• IF VRSA : LINEZOLID.
 CYSTIC FIBROSIS

• Genetic disorder
• Autosomal recessive
• CF TR Gene defect on chromosome 7
• CF transmembrane conductance regulator-encode for Cl- channels.
• The defect in Cl channels cause very thick secretion(obstruction)
known as Mucoviscidosis.

Clinical features :
• Newborn fail to pass meconium(>48hrs) known as Meconium Ileus.
• Biliary Obstruction-Cirrhosis, Jaundice, Fat malabsorption, Cholestasis etc..
¥ Features associated with diabetes mellitus(pancreatic insufÞciency).
• Infertility/sterility-in females thick cerbical mucus and in males absence of
vas deferens.
• Increased respiratory infection due to thick mucus obstruction in airway
causes bronchiectasis.
Investigations :
1. Sweat test :
Cl levels in sweat >60mEq/l in cystic Þbrosis.
2. Nasal epithelium potential difference.
3. Genetic analysis : (ConÞrmatory Test).

Treatment :
• Mucolytics.
• Antibiotics.
• Lung transplant
• New drug : Ivacaftor :- It increase conductance of Cl- channels
 • ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
• HYALINE MEMBRANE DISEASE/ SHOCK LUNG STIFF LUNG
• DIFFUESE ALVEOLAR DAMAGE/ ACUTE LUNG INJURY

Causes :

• Can be non-infectious
¥ DeÞciency of surfactant in newborns cause hyaline mebrane disease.
• Overall MCC : Septicaemia.
• Other causes : - Infections(covid-19)
- Trauma, shock,
- DIC, Vasculitis.
- Iatrogenic.
Pathophysiology :
• Damage to type I pneumocytes(makes alveoli) and Type II(makes surfactant).
• Also affect pulmonary capillaries.
• Damage to Type II pneumocytes cause less surfactants
• Decreased surfactants lead ro atelectasis(collapsed lung) due to increased
surface tension
¥ Fibrin and edema ßuid create hyaline membrane
• Poor oxygen diffusion causes respiratory distress.
• Damage to Type-I Pneumocytes causes poor diffusion of oxygen and hence
respiratory distress.
¥ Fluid increases capillary permeability, cause protein rich ßuid enter the
interstitium & alveoli cause non cardiogenic pulmonary edema(normal
Pulmonary Capillary Wedge Pressure).
¥ InÞltration by WBC (neutrophils,lymphocytes)
¥ Inßammatory changes(increased CRP)
• Activate clotting pathway -thromboembolism,
¥ SpeciÞcally, Microthrombi/emboli.
• It is very serious complication of Covid-19.
• All these changes reduce oxygen exchange and cause hypoxic hypoxia
 Patient will compensate by hyperventilation
#
Increased respiratory muslce work(distress)
#
If muscle fatigue occurs
#
Poor ventilation
#
Respiratory Failure Type-II

Severity of ARDS

• PaO2/FiO2 ratio:
- Normal PaO2=95-98mmhg FiO2 ! 21%.
• In normal person,ratio is 100/0.2=500mmHg
• In ARDS,poor diffusion cause decreased PaO2
• Based on level of damage,the PaO2 would be low even if we increase the FiO2
by oxygen therapy
i,e, FiO2 0.2(20%),PaO2 60mmHg=60/0.2=300mmHg low. Increase
FiO2(40%) but PaO2 low
• Patient A : 50/0.4=125mmHg (more severe).
• Patient B : 100/0.4=250mmHg (less severe).

Three grades of ARDS

1. Mild : <300mmHg.
2. Moderate : <200mmHg
3. Severe : <100mmHg.
Clinical features :

• Similar to pneumonia
• Fever if infection present,covid-19 cause high grade fever.
• Increased RR decreased SpO2
• Respiratory distress-use of accessory muscles,chest retraction,
grunting sound, nasal ßaring Cyanosis etc.

Investigations :

• HRCT : Ground glass opacity B/L diffuse due to inÞltration.

• Sputum/ Bronchoalveolar
lavage

COVID-19

• Corona virus : bind ACE-2 Receptor via Spike protein.It mainly infect
respiratory epithelia. Naso/oropharynx etc.It can affect almost all body systems.
Eye : Conjuctivitis
Lungs : ARDS &pneumonia damage due to cytokine storm increased CRP,
IL-5, IL-6,D-dimer etc.
CVS : Thromboembolism etc..
Investigation for COVID-19 CORADS : HRCT radiology for COVID-19
- Most sensitive & conÞrmatory is RT-PCR.
- Severity on the basis of SpO2, RR.
Treatment :
• Prone position ventilation.
• Oxygen therapy.
• CPAP Antibiotics-if bacterial cause of ARDS.
• If covid-19 : Remdesiver.

PULMONARY EMBOLISM

¥ Reduced blood ßow to lungs cause reduced Gas Exchange (Dyspnea,central

cyanosis)
• Also death of Ischemia pulmonary tissue.
• Infarction and pleural effusion(U/L)

Causes :

• DVT
• Fractures-if within 24-48 hours then it is Fat embolism causing pulmonary
embolism,After that,immobilization cause DVT.
• Cardiopulmonary disease-A.Fib,Infective endocarditis
• Pregnancy, OCP, Varicose vein, SLE.
• Thromboembolism : Virchow’s triad
1 Stasis of blood.
2 Endothelial injury.
3 Hypercoagulation.
Clinical Features :

• Severe,sudden onset dyspnea U/L chest pain,low BP, increased HR,

Syncope,cyanosis.
• DVT present : Erythema pain, swollen limb.
Investigation :
• Gold standard : CT Pulmonary Angiography.
• Perfusion scanning, D-dimer, Fibrin degradation product.
• Xray/CT :- Pleural effusion.
- Hampton’s hump : Wedge shaped opacity.
• Dilated pulmonary vessel proximal to emboli : Fleischner westmark sign.

• ECG : right bundle branch block(pulmonary embolism ECG is similar to inferior

wall MI

S in lead-I.
Q in lead-III.
T inversion in lead-III.
No ST Elevation.
Treatment :

¥ 100% oxygen,opioids,ßuids Thrombolysis-streptokinase,alteplase/reteplase Anti

Coagulant : Aspirins, IV unfractionated heparin Once patient stable :
warfarin Heparin-act via anti thrombin III.
- Inhibit clotting factor 9,10,11,12.
- Inhibit intrinsic clotting pathway.

• aPTT for monitoring activated partial thromboplastin time.

• Warfarin inhibits vitamin K,inhibits factor 2 Monitored by PT and INR.
 PLEURAL EFFUSION
• Fluid in pleural cavity.

Types :
1. Exudative(inßammatory)
2. Transudate(non-inßammatory,mainly organ failure)
3. Blood called as Hemothorax.
4. Pus called as empyema.
5. Chylothorax

LIGHT’S CRITERIA : Differentiate Transudate & Exudate.

Investigation :
• Pleural Tap:diagnostic/therapeutic.
¥ USG is best at ßuid detection
¥ Then Xray : lateral decubitus,blunting of CP angle,ßuid level.
Treatment :

¥ Antibiotics(for infection)chest tube insertion for draining the ßuid.

 TUBERCULOSIS

• Poor immunity patients,old,children

• HIV patients: MAC(mycobacterium complex)
• TB by aerobic bacteria(M.tuberculosis)
• LJ medium (green slope)
• Colonies:rough,tough,buff,colonies
• ZN Stain(acid fast bacillus,red rods)
• Main virulence is due to mycolic acid(cord factors).
• Infection is by droplet,MC site is upper lobe junction with middle lobe.
• The mycolic acid prevent killing & phagocytosis by macrophages.
¥ As a result cause chronic inßammation/delayed or cell mediated HD Type-IV.
¥ Chronic inßammation leads to granuloma formation, Caseous necrosis,
epitheloid rods, macrophages, giant cells, lymphocytes etc.
• Patient has evening fever, Cough with Sputum or Hemoptysis.
• weakness, weight loss.

Primary TB :

• healing occurs,patient revovers

¥ Xray-calciÞcation,Þbrosis
• Gohn’s focus : At junction of upper middle lobe and if involved lymphatics
known as Gohn’s complex.

Secondary TB :

• Reactivation due to immunity.

• It causes cavity formation/consolidation.
• Miliary TB (disseminated via blood).
¥ Lung Þbrosis/collapse/infarct/pulmonary effusion.
• Extra pulmonary TB : Any organ.
Investigation :
• Chest xray
• Sputum culture and microscopy.
• Tuberculin or Mantoux test.
- Cause induration>10mm
¥ ConÞrmatory : CBNAAT also Genotype GST,PCT can be used.

Gohn’s Complex Miliary TB

Mantoux test.
Treatment :
• ATT , HRZES.

• Multidrug resistance : both isoniazid(H) and Rifampicin(R).

• Extreme drug resistant : 4 drugs H,R, 1-Injectables & 1 Fluoroquinolone.

 5 NEPHROLOGY

• Clear plasma of waste and form urine by :

1. GlomerularÞltration.
2. Tubular reabsorption.

Three types of diseases :

1. Pre-renal :
¥ Less blood ßow.
• Shock, HF.

2. Renal :
• Tubular.
• Glomerular.
• Vascular.

3. Post-renal :
• Urinary obstruction.
• Calculi, BPH, Infection etc…

• If kidneys cannot function, there would be accumulation of nitrogeneous

waste. Eg : Urea, Uric acid, Creatinine : known as Azotemia.
Kidney Function Test :
• Serum urea : 20-40mg%.
• Serum uric acid : 4-8mg%.
• Serum creatinine : 0.5-1mg%
• Blood urea nitrogen(BUN) : Roughly half of blood urea10-20mg%.
• Urine creatine/serum creatine ratio : 10-20 times.
• BUN/S.Creatinine ratio : 10-20 times.
¥ Urine speciÞc gravity : 1010-1020gm/ml or 1.010.

Anti Diuretic Hormone :

¥ Coming from posterior pitutary(supraoptic nerve).
• Controls urine output and urine osmolarity
• Acts via :
1. V-1 Receptor which cause : Vasoconstriction.
2. V-2 Receptor : Increases aquaporin-2 in collecting tubules of kidney.
- V2 in turn increases water reabsorprion and causes low
volume, Concentrated hypertonic Urine.

Range of urine osmolarity :

• Hypotonic : Less or no ADH= 50mosm/L.
• Hypertonic : More ADH= 1200mosm/L.

Normal urine output : 1-2L/day or 40-60ml/hr.

• Weight wise : 1-2ml/kg/hr.
• In case of Renal Injury : <0.5ml/kg/hr.
• In Renal Failure : 0.3ml/kg/hr.
• Oliguria = 400ml/day
• Polyuria = 3L/day or >2ml/kg/hour.
ADH DISORDERS

DIABETES INSIPIDUS

1. Neurogenico/Central DI : Less ADH from pituitary gland.

2. Nephrogenic DI : Normal ADH but fail to act on kidney.

Clinical features :

• Less water reabsorption cause polyuria, polydipsia, dehydration, low osmolarity

urine(<500mosm/l).
¥ Low speciÞc gravity <1010
• Increased plasma osmolarity >300mosm/L
¥ Normal value(285-295)

Treatment :
• Neurogenic DI : DOC = Desmopressin(V2)
• Nephrogenic DI : DOC = Thiazides.
- Thiazides initially causes sodium loss,compensatory increase and water
reabsorption and reduce polyuria.
• Lithium induced DI : DOC Amiloride(also DOC in Liddle Syndrome).
 SIADH
SYNDROME OF INAPPROPRIATE ADH STIMULATION

¥ Increased ADH levels : Because of Pituitary Adenoma and Paraneoplastic syndrome.

Cause :
• More water reabsorption.
¥ Low urine volume
• Hypertonic urine>600mosm/l
¥ High urine speciÞc gravity >1020(weight of urine compared to distilled water).
• Dilution hyponatremia due to more water entering blood from kidneys.
- hence decreased plasma osmolarity <280mosm/L and decreased
Serum sodium <125mEq/L.
• Low osmolarity leads to water entry(osmosis)into cells & neurons cause cell
swelling/ edema & injury and in brain it causes Central pontine myelinosis.

Treatment :
• Hypertonic saline to increase serum sodium 3/5% saline.
• DOC : Vasopressin antagonists called as VAPTANS
Eg : Conivaptan, Tolvaptan.
 GLOMERULAR FILTRATION RATE

• Normal=125/min or 180L/day
• GFR estimation:best is Inulin Clearance (<1)
• But clinically most commonly jsed is creatinine clearance because creatinine is
endogenous.
Various formulae/ Equations used for GFR estimation :
¥ CKD-EPI,MDRD-II Equations : They Gives eGFR(estimated GFR)corrected for
age sex etc.

• MDRD :

• Cockcroft-Gault :

• CKD-EPI :

Radio isotopes based renal studies :

1. Dimercaptosuccinic acid(DMSA) : Best for renal morphology.
2. DTPA : For renal perfusion,GFR functions.
3. MAG-3 : for renal failure

DMSA DTPA
¥ Sodium balance-tubules reabsorbs 99% of Þltered sodium &<1% of sodium is
excreted in urine known as Fractional Excretion of sodium.
• Normal urine sodium=10-20mmol/L.
• Tubular disease/lesion cause FENa+ >1% amd increased urine sodium.

ACUTE TUBULAR NECROSIS

• MCC : NSAIDs.

Paracetamol
#
Prostaglandin levels cause vasoconstriction
#
Cause ischemiac& necrosis of tubular cells.
#
Less reabsorprion of Na+ water &other solutes (Polyurea with loss of
water,sodium &other ions)
#
Urinary sodium >30mmol/L : Hyponatremia.
FENa+ >1% : Hypotension.

Treatment :
¥ Stop drugs,give electrolyte supplement.
• DOC : N-acetyl Cysteine.
 ACID BASE BALANCE

¥ Tubules prevent or correct acidosis by HCO3.

• Reabsorption using carbonic anhydrase & secrete H+ in urine
¥ Urine acidiÞcation occur in distal tubule
#
• Make acidic urine upto pH 4.5 knkwn as limiting pH.
• Aldosterone cause : increased acid and K+ secretion Tubular lesion causes less acid
secretion,less HCO3- reabsorption,hence increased H+ in blood,decreased HCO3-
in blood(metabolic acidosis due to tubular damage hence Renal Tubular Acidosis.
• Loss of bicarbonates in urine is known as Bicarbonaturia.

Renal tubular acidosis

- Normal plasma anion gap(NAGMA)& Increased urine anion gap due
to ammonia.
- Also K+ loss : Hypokalemia in RTA-I & II.
• RTA-I is distal tubule lesion.
• RTA-II is Proximal convoluted tubule lesion.
• RTA-I +RTA-II : RTA-III(Mixed RTA).
¥ RTA-IV- deÞciency of aldosterone.
Eg : Addisson’s disease (hyponatremia and hyperkalemia).
• Treatment : DOC - Hydrocortisone, HCO3-

SUMMARY
Hyperkalemia : RTA-IV
Hypokalemia : RTA-I & II
#

CHECK URINE PH
• PH : >5.5 = RTA-1.
• PH : <5.5 = RTA-II.
Three types of Azotemia
 ACUTE RENAL FAILURE

• Also known as Acute kidney injury.

• Acute : <3months.
• RIFLE criteria : (Risk injury failure loss end).
- LOSS : >4weeks of ARF.
- END : >3months of ARF.
- Rx : Renal transplant or dialysis till donor available.

For RIF we check##GFR, S.CREATININE,#URINE OUTPUT

#

#GFR #
S.CREATININE # Urine Output

>2.5% dec 1.5 times <0.5ml/kg*6h

RISK

INJURY >50% dec 2 times 0.5mk/kg*12h

FAILURE >75%dec 3 times 0.3ml/kg*24h

Clinical features :

• Oliguria/Anuria,Huperuricemia : Gout
• Urea (uraemia : uremic encephalopathy(confusionMemory loss, delerium,
tremors, coma).
• Uremic pericarditis, Palpitations.
• Uremic frost on skin : urea precipitation sweat(urea smell).dry,itching skin.
¥ Nausea,vomitting,abdominal pain
• Hyperkalemia,metabolic acidosis with respiratory compensation.
• Anemia due to decreased erythropoetin(causes RBC Production).
 ¥ If Pre-renal Þndings of shock/heart failure.
¥ If renal(post-renal) : ßuid overload, HTN, Edema on face.
• Osteoporosis due to low calcium & phosphorous.
¥ Reproductive system : decreased libido, Impotence.
¥ Ovulation failure(high urea supress pitutary).

Investigation :
• Kidney function test.
• Urine examination to check proteinuria, Casts, hematuria etc..

Treatment :

• Always correct the underlying cause.

• Fluid and electrolyte correction.
• Diuretics-increase urine output.
• ACEI/ARBs.
• Recombinant erythropoetin for anemia correction.
• Metabolic acidosis by HCO3-
• Correct hyperkalemia : If ECG changes present, Ist give Ca gluconate10%.
- DOC : Insulin + beta 2 agonist salbutamol.
• Correct hyperuricemia/Gout.
- DOC : Allopurinol(xanthine oxidase inhibitor).
• Correct Calcium : Ca2+,PO43- Vit.D suppliments for osteoporosis.
• Scleroderma crisis : DOC ACEI/ARB
• Rhabdomyolysis : forced alkaline diuresis.
¥ Dialysis-using artiÞcial membrane to remove wastes.
Indications of dialysis : AEIOU

• A : Acidosis(Refractory)
• E : Electrolyte imbalance-refractory hyperkalemia
• I : Intoxication-barbiturates,theophylline,aspirin,INN, lithium
• O : Oedema-pulmonary edema
• U : Uremic pericarditis &encephalopathy For dialysis,we make AV Þstula/graft.

New markers of Kidney Disease :

• Kidney Injury Molecule(KIM-1).
• Cystatin-D.
• NGAL from neutrophils.
• IL-8.
• L-Type fatty acid binding protein(LFABP).
 Hepato Renal Syndrome

¥ Renal failure secondary to liver disease like cirrhosis Decreased GFR and urine
output,increased S.Creatinine,but no morphological defect.

Pathophysiology :
¥ RAAS, Toxins which were metabolized by liver would accumulate and
damage nephrons.
¥ Also increased sympathetic activity involved.
¥ There is renal vasoconstriction,Pre-renal azotemia.
 CHRONIC KIDNEY DISEASE

• Duration >3months

GFR ALBUMINURIA
[PROTEINURIA) >30mg/day.
(<90ml/min)
Albumin/creat ratio mg/gm].

• Grade I " 90ml/min(normal) • Grade A1 <30mg/gm (mild)

¥ Grade II 60-89 (Mild) • Grade A2 30-300mg/gm(mod)
¥ Grade III 30-59 (moderate) ¥ Garde A3 >300mg/gm(severe)
¥ Grade IV 15-29(severe)
• Grade V <15 (failure)

Causes of CKD :
• MCC : Diabetes mellitus : Kimmelstein Wilson Nodular Glomerulosclerosis.
- Polyuria(increased GFR).
- Proteinuria(decreased GFR).
¥ Hypertension-ßea bitten kidney Glomerulonephrosis
• Chronic UTI/ Obstruction.
• PCKD

Management Of CKD :
• Control BP(DOC-ACEI/ARBs).
• Correct blood sugar
• Correct hyperkalemia & acidosis.
• Protein and salt restriction
• Allopurinol
• Erythropoetin
¥ Calcium,phosphorous,vitamin D for osteoporosis
• Dialysis
• Renal transplant if S.creat >10mg% &BUN >36mmol/l
 STAGES OF CHRONIC KIDNEY DISEASE

TUBULAR DISORDER

LIDDLE SYNDROME
• Autosomal dominant
• Mutation in beta and gamma subunits of ENaC
¥ It prevents breakdown of ENac(increases activity).
• Increased sodium reabsorption(resembles Conn’s)
• Hypernatremia,hypertension,metabolic alkalosis
• But aldosterone normal,hence liddle supyndrome also
known as PSEUDO HYPERALDOSTERONISM.
• DOC : AMILORIDE.
BARTER SYNDROME
• Resembles loop diuretics.
¥ Bartin gene defect,decreased activity of nKCC(Na+,K+,Cl-, co transporter.
• Loss ofnsodium,water & all solutes in urine (hyponatremia, hypokalemia,
hypocalcemia, hypochloremia).
• Also fails to concentrate the urine -isotonic urine
• Increased expression of PGE2
• Cl Resistant metabolic alkalosis
Clinical features :
• Age of presentation : early life.
• Polyuria,polydypsia,hypokalemia(muscle weakness & wasting)
Sensorineural hearing loss.
Treatment :
• Indomethacin-inhibit PGE2.
• ACEI/ARB.
• Renal transplant.
GITELMAN SYNDROME
• Looks like thiazides
¥ Autosomal ressecive
• Defect in NCC in early DCT(Na+Cl-Co transporter)
• Loss of all ions in urine except Ca2+
• Different from Barter:normal PGE2 & increased S.Ca2+
Treatment :
• Similiar to barter
• No indomethacin and Ca2+ suppliments.
SUMMARY

1. Liddle Syndrome
• Increase Sodium.
• Decrease Potassium.
2. Bartter Syndrome
• Decrease Sodium.
• Decrease Potassium.
• Decrease Calcium.
• Decrease Chloride.
3. Gitelman Syndrome
• Increase Calcium.
• Other : Decrease.
 GLOMERULAR DISEASE

NEPHROTIC SYNDROME NEPHRITIC SYNDROME

• Mainly proteinuria. • Proteinuria with hematuria(RBC cast)
• No hematuria(rare). • Cola coloured urine
• No hypertension. • Hypertension

• Gross proteinuria>3.5gm/day. • Sub nephrotic proteinuria<3.5

¥ Selective Proteinuria
¥ Non-selective
(Mainly albuminuria)
• Lipiduria/ fat lost/ Hyperlipidemian. • Absent
• Loss of protein C & S High risk
• Absent
of thrombosis.
• Lower immunity & high infection. • Absent
• Facial edema(periorbital). • Less edema
• Steroids,immunosuppressants, • ACEI/ARB,Steroids,
dietary suppliments. Immunosuppressants.

NEPHROTIC SYNDROME
¥ Overall MCC : Diabetic nephropathy.
• Children : Minimal change disease.
• Adult : Focal segmental glomerulosclerosis.
 MINIMAL CHANGE DISEASE

Causes :
• Mainly : Idiopathic.
• Autoimmune.
• Infections.
• Drugs.

Pathophysiology :
¥ Damage to Podocytes & loss of negative charge in glomerular membrane.
This cause Þlling of negatively charged albumin.

NORMAL MCD

LAB Diagnosis :
• On light microscopy : Minimal or No Þndings.
• On electron microscopy : Effacement of foot process of podocytes, microvilli &
vacuole formation.
Clinical features :

• Young child(5-15yrs) Presents with edema, periorbital swelling, Decreased

plasma albumin, muscle wasting, poor growth, increased infection
• Investigation : Urine protein>3.5gm/day.
Treatment :
• DOC : Steroids : Prednisolone : 1m/kg/day
• If steroid resistant, immunosuppressants (cyclophosphamide, Azathioprim,
Tacrolimus, cyclosporin).
• Monoclonal antibody : Rituximab
• Statins for dyslipidemia, Protein suppliments.

Adults have : FSGS (Focal Segmental Glomerulosclerosis)

• Similar to MCD.
¥ Foci of hyaline deposition, increased matrix Segmental collapse of vessels and
podocyte damage.
• Treatment : Steroids, Immunosuppressants.

FSGS
NEPHRITIC SYNDROME
• MCC in children: (PSGN)
Post Streptococcal Glomerulonephritis
• Streptococcal infection (pharyngitis,impetigo etc..)
¥ S. pneumoniae,S.pyogens,S.viridens.

• After Infection 4-6 weeks : cola coloured urine, RBC casts, edema
Proteinuria<3.5gm/day, decreased compliment protein]
• Type III HS-immune complex deposits & damage to glomerulus.
• Hypertension
• ASO titre(anti streptolysin-O)
• Treatment : ACE-I/ARB, Steroids, Immunosuppressants, Antibiotics.
 BERGERS DISEASE

• Also known as IgA nephropathy

• MCC of nephritic syndrome in adults.
• Similar to PSGN : Upper respiratory tract infection (Hematuria,
proteinuria,hypertension etc).
Biopsy : IgA deposits in mesangium on immunoßuresnece.
- Also cellular crescents(main).
Treatment : ACE-I/ ARB, Steroids, Immunosuppressants.
 GOOD PASTURE SYNDROME
• Anti-GBM antibody syndrome(glomerular basement membrane).
• Anti Pulmonary BM Ab syndrome.
¥ Destroy glomerulus : hematuria (nephritic Syndrome, HTN,selective proteinuria)
• It causes rapidly progressibe GN : Renal failure.
Treatment : ACE-I/ARB, Steroids, Immunosuppressants, Antibiotics.

• NEPHRITIC SYNDROME : SLE, HSP, ANCA Vasculitis, PAN.

 ACID BASE DISEASE

Arterial Blood Gas Analysis (ABG)

• Respiratory system prevent acidosis by removing carbonic acid as CO2 known as

CO2 washout.
H2CO3 ! CO2+H20
• High PaCO2 would produce Respiratory Acidosis.
• Eg : Respiratory disease which cause hypoventilation [high PaCO2, Low pH].
• In case of hyperventilation,it causes high CO2 washout causing Respiratory
Alkalosis:decreased PaCO2,,increased pH(>7.5)
• HCO3- acts as buffer and prevent acidosis by neutralizing H+ ,kidney regulate
HCO3- leaves by reabsorption

H + HCO3- H2CO3 CO2 + H2O

(Removed by Lungs)

• So, Metabolic Acidosis : Low HCO3 (used as buffer).

• Metabolic Alkalosis : High HCO3

• PaCO2 : Rspiratory acidosis.

• PaCO2 : Respiratory alkalosis.
• HCO3- : Metabolic acidosis.
• HCO3- : Metabolic alkalosis.
• If low HCO3 and high PaCO2 (metabolic acidosis + Respiratory acidosis) known as
mixed Acidosis : Opposite Direction, Low HCO3, high PaCO2
• In metabolic disorders, Respiration would try to compensate and vice versa.
• Acidosis compensates alkalosis.
• Alkalosis compensates acidosis.
• Example : Metabolic acidosis PH & HCO3

• Resporation would try to remove acid by hyperventilation: PaCO2 (Respiratory

Alkalosis) or Compensated Metabolic Acidosis.

Compensated
Respiratory Acidosis Metabolic alkalosis
( PaCO2) ( HCO3)

Compensated
Metabolic Acidosis Respiratory alkalosis
( HCO3) ( PaCO2)

• Hence, Compensation of HCO3 and PaCO2 : Same direction.

In mixed acidosis
• Respiratory acidosis + Metabolic acidosis : Opposite direction.
( PaCO2) ( HCO3)

PH HCO3 PaCO2 Diagnosis

 PH

Metabolic Acidosis Respiratory Acidosis

HCO3 PaCO2

Check PaCO2 Check HCO3-

Low-compensated metabolic High-Compensated Respiratory

Acidosis. Acidosis
• Normal-uncompensated. • Normal : Uncompensated.
• High-mixed metabolic • Low : Mixed Respiratory Acidosis.
Acidosis.

• If HCO3- and PaCO2 are in same direction : Shows compensation.

• If all 3 are low (PH,HCO3-,PaCO2) are abnormal : Partially compensated.
• If HCO3- and PaCO2 but pH normal : Fully Compensated.
• If HCO3- or PaCO2 one normal other abnormal: Uncompensated.

• Amount of compensation=Winter’s formula.

• Expected PaCo2 =HCO3-level*1.5)+(8±2).

SUMMARY
 ANION GAP IN METABOLIC ACIDOSIS

• Anion gap= Na+ -(Cl- +HCO3-).

• Normal Na+ =125-145mEq/l (135 avg).
• Normal Cl- = 100-110mEq/L.
• Normal Anion Gap is 8-14(16).

There are two types of metabolic acidosis:

1. Normal Anion Gap NAGMA(RAAD) :

• GIT and kidney tubule disease.
• HCO3- loss occur : Metabolic acidosis.
• But there is Cl gain to compensate,hence Anion gap normal.

• Renal tubular acidosis

• Addison’s disease-low aldosterone
• Acetazolamide- Carbonic anhydrase inhibitor
• Diarrhoea : loss of alkaline secretions,intestinal secretions causing loss of
HCO3 : Increase Cl re- absorption.
¥ Enteric or pancreatic Þstula
• In all these cases, tubules fails to secrete acid(H+) and HCO3- loss occurs
and Increases Cl- reabsorption.

2. High anion Gap(HAGMA) (Non RAAD) :

• Loss of HCO3- but no gain of Cl , Mostly organic acids or foreign acids.

Eg :
• Diabetic ketoacidosis (HCO3 low, no gain of Cl-).
• Lactic acidosis
• Starvation (Increased ketoacidosis).
• Alcohol (Ethanol and methanol).
 • Glycol/ethylene/propylene used as anti freeze.
¥ Glue snifÞng(aromatic compound like thinner,varnish).
• Isoniazid’s, Iron, Paraldehyde, Aspirin, Salicylic acid.

Treatment :

• If respiratory acidosis-always correct the cause.

- Increase ventilation- assisted breathing/ventilation/CPAP
¥ If metabolic acidosis : Correct the cause of DKA-insulin and ßuids.
- Use HCO3- Soda bicarbonate,potassium bicarbonate Ist calculate base
defect : 24 - HCO3- level
Eg : 14mEq/L
DeÞcit : 24-14=10
Correction of bicarbonate = deÞcit * half body weight.
Eg : body wt= 60kg Correction = 10*30=300mEq.

ALKALOSIS

Low PaCO2. High HCO3-

Respiratory Alkalosis Metabolic alkalosis

Check HCO3- Check PaCO2

Low-compensated Respiratory Low-Mixed alkalosis High-

Alkalosis. comoensated
• High : Compensated Metabolic
• High : Mixed alkalosis. alkalosis
• Normal : uncompensated Respiratory • Normal : uncompensated.
Alkalosis

• If normal pH : Fully compensated.

• If abnormal pH : Partially compensated.
Causes of Respiratory Alkalosis :
• Hyperventilation : Causes CO2 washout Anxiety attack cause
hyperventilation.
Rx : IV lorazepam(benzodiazepine).
• Respiratory disorders : Asthma, Emphysema.
• High altitude/mountain sickness
• Low oxygen causes : Hypoxic hypoxia.

Hyperventilation Pulmonary Edema

and Cerebral edema

• CO2 Washout. • MCC of death.

• DOC : Create metabolic • Most dangerous
acidosis by Acetazolamide • Dizziness, headache,
• Nausea,
• Altered sensorium

Metabolic Alkalosis
• Gastric vomitting : HCl loss
(Eg : pyloric stenosis, Hypochloremic metabolic alkalosis.
• Increased aldosterone : Conn’s syndrome.
• Liddle syndrome.
• Loop diuretics and thiazides.
• Bartter syndrome.
• Gitelmann syndrome

Rx : Treat the cause.

- Electrolyte replacement.
2 ENDOCRINOLOGY

DIABETIC

• " Urination : Both "volume and "frequency.

2 Types of Diabetes

Diabetes Mellitus. Diabetes Insipidus.

¥ Abnormal Sugar proÞle ¥ Normal sugar proÞle but

due to : Insulin Defect . ADW Defect.

1. Diabetes Mellitus.

Disorder of Insulin

• Less Insulin : DM-I

• Insulin Fail to act : DM-II

• Insulin shift K and Glucose from blood to cells : Hypokalemia & Hypoglycemia
(<7omg%) !Glucose to cells
via GLUT- 4
Cell get glucose for metabolism (satiety)
Growth and Store energy (weight gain).

• Glucose won't enter cells it remains in blood : Hyperglycemia.

• thus, Hunger cause : Polyphagia.
Hyperglycemia

1. Glucose Excreted in urine called as : Glycosuria/ Glucosuria.

("urine output (osmotic diuresis)]
- Polyuria(>3L/day)

2. Dehydration,!Plasmaosmolarity !Thrust & Drinking : Polydipsia

3. Blood glucose bind non-enzymatically (very slow) to proteins

- Ex : Mb-A, lipids, membranes etc, & damage them.
• This cause : Nephropathy , Retinopathy, Angiopathy (Take years to decades).

4. Poor Immunity & wound healing.

Clinical feature :

Traid : 1. Polynesia.
2. Polydipsia.
3. Weight Loss.
• Polyphagia.
• ""Infection.
• Poor wound healing.
• # energy,etc.

Diagnosis : Blood sugar ProÞle

1. Fasting BS (8-12 hrs without food).

• Normal : <100mg%
• DM : >126mg%
• Pre DM : >100 - 125mg%
2. GTT (Glucose Tolerance Test)

• Oral glucose (75gm)!check B.sugar then & after 2hrs.

• Normal : <140mg%
• DM : >200mg%
• ImpairedDM : 140-199mg%
• Pre-DM(Impaired).
an'tHandle glucose properly Hence :"Glucose level.

3. RBS (RandomBs) (Anytime done)

• Similar to GIT DM >200mg%.

• Best for Diagnosis is HbA1c,(glycated Hb)
• HbA1C indicate Glycemic status over Past 3months Bcoz it is
formed by slow binding of Glucose with Hb.

Uses of HbA1c :
1. Diagnosis
2. Treatment on the basis of HbA1c level.
3. Prognosis low HbA1c : better survival.
4. Severity (LowHbA1c means less severe).

• Short team Glycemic status of control of 2weeks, we use S.Fructosamine.

• Long term glycemic control : 3month by HbA1c.

• Normal HbA1c: <5.6%

• DM : >6.5%
• Pre DM : 5.7-6.4%
 SUMMARY

HbA1c FBS GTT

1. DM >6.5% >126mg% >200mg%

2. NORMAL <5.6% <100mg% <140mg%

3. IMPAIRED 5.7-6.4. 100-125mg% 140-199%

Diabetes Mellitus : 2 main Types :

1. Diabetes Mellitus-I
• less Insulin production dlt destruction of beta cells .
• Mostly Autoimmune, TypeII (HS), HLA1 DO-A1, DR-3 & DR-4.
• Autoantibody :
- Against Islet cell Abs (ICA)
- Insulin AutoAbe (IAA)
- GAD Antibody (Glutamic Acid Decarboxylase).
DM-IA: AutoImmune
DM-IB: Idiopathic

2. Diabetes Mellitus-II

• Normal / High Insulin but fail to Act as tissue c/a Insulin Resistance.
• Ex- Obesity, Resistin , TNF alpha (Inßammation) leptin defect etc.
• Most Patients have Genetic Basis so , family History Present.
• Most likely mechanism of Insulin Resistance is Down regulation of
Insulin Receptor DeÞnes a high Insulin need levels >100units/day.
 DM-I DM-II

Insulin & C-Peptide • ### • Normal/ ""

Insulin • Sensitive • Resistance

( Insulin can act)

Other Name • IDDM • NON-IDDM

( Insulin dependent DM)

Patho • Autoimmune AutoAb + • Gene / family history.

Age • Middle Age

• Children / Adolescent (10-15 years)
(40-50years)

Weight • Thin, Stunted,wasted • Obese (then resistance

& DM-II)

Prevelence • 5% • 95% (m/c)

DKA
(D.ketoacidosis) • +++ m/c. • +

Treatment • Insulin.

3. LADA (Latent Autoimmune DM of Adult) :

• DM-I in Elderly.
• Autoimmune, GAD Ab!
• Less Insulin , Sensitive Treatment Insulin.
4. MODY (Maturity onset DM of Young).

• AD
• Age <25years
• NO Abs, No Autoimmune
• Genetic D: AD — Family history +ve.
• 6 sub types: MC is type 3.
• HNF-alpha gene defect:Hepatocyte Nuclear factor-alpha ! less Insulin ,
No obesity, Insulin sensitive
• Rx-Insulin.

NOTE
• Except DM-II All have low Insulin & Insulin Sensitive
• Rx- Insulin (DM-I, MODY , LADAD).

SUMMARY
Autoimmune Genetic/Family History ( No Abs)

Young • DM-1 • MODY

Old • LADA (GADA) • DM-II

(only in Insulin Resistance)

Treatment :
1. Insulin : DOC for DM-I, MODY, LADA,DKA ,Resistant DM-II
Hyperkalemia, Gestational Diabetes
 • Best Method for Insulin Delivery is Insulin pump, At Abdomen/thigh It is
smart device sense glucose and Release Insulin.

• Regular Insulin given by Intra-dermal

injection (very painful) ! t1/2=2-5min.

• Longer Acting Insulin : Glargin (t1/2 : 24 -28 hrs).

• longestActing : Degludec (t1/2 : 40-48 hour).
• Ultra short acting : Aspart/ Lispro Insulin.

Treatment For DM-I :

1. life style modiÞcation
2. Weight loss, Bariatric surgery.
3. Avoid sedentary lifestyle.
4. "Physical Activity.
5. Control BP
6. Correct lipid proÞle : Most DM-II

• DM-II haveDyslipidemia( #HDL, "LDL, "VDL, "S.cholesterol & TG).

• HDL = Good cholesterol coz it take cholesterol from tissue (vessel) to liver.
• It prevent Atherosclerosis.
• DOC - STATINS
- ("HmG COA Reductase& #cholesterol synthesis)
7. Stop smoking & Alcohol.
8. Dietary control:"Salt Intake low Glycemic Index food (Raw & non sweet]
Ex : Salad , Oats.
9. Advice small frequent meal.

Treatment For DM-II :

Oral Hypoglycemic Agents

1. Biguanides:
Metformin (DOC for DM-II).
Phenformin (Banned)
MOA : Reduce glucose output from liver = Hypoglycemia & weight loss.
S/E : lacticacidosis,vitB12def.
C/I : Alcoholics, Pregnant, liver / kidney disease.

2. SGLT 2 inhibitor :

• Prevent glucose Reabsorption in kidney.

¥ Glucose ßow out in urine : Hypoglycemia.
• Glißozine
Ex : Canaglißozin, Dapaglißozin.
 • They are used as replacement of metformin.
• S/E : "Glucose in urine cause UTI.

3. Sulphonyl Urea :

• Glibenclamide, Tolbutamide , Glimepiride, Glipizide.

• MOA : K+ channel blockers : ""Insulin Release.
• It Can be used with Metformin.

4. TZD :
• Rosiglitazone, Pioglitazone
• can be used with metformin.
• MOA : "Insulin sensitivity & #Resistance.

5. AGI (alpha Glucosidase inhibitor) :

• Inhibit Digestion & Absorption in Carb/starch, they prevent Hyperglycemia

by not letting Glucose come to blood from GIT.
• Acarbose , miglitol etc.
• S/E : Flatulence, Diarrhea, Bloating.

6. Pramlintide :
Amylin Agonist
#
• " Gastric Emptying & slows glucose Absorption in GIT.
• It Prevent Postprandial Hyperglycemia.
• Can be used in DM-I & AGI also
7. DDP-IV Inhibitor (Di-Peptidyl peptidase).
• GLP-1&GIPareGITHormoneswhich "Insulin&#Appetite.
• DPP-IV break GLP-1 & GIP so, DPP-IV" will "GLP & GIP and
correct Diabetes Called as GLIPTINS
• SITAGLIPTIN
• Saxagliptin
• Vildagliptin
• LINAgliptin(also used in Renaldisease).

6. GLP-1 Agonist :

• LIRAGlutide, Exenatide

MANAGEMENT OF DM-II :

1. life stiße, wt loss , Diet etc.

- Rx Goal is HbA1c <7%.

Metformin : for 3month

#

If not controlled add Another OHA (S.Urea/TZD/DPP-V inhibitor)

#

Metformin + 2 OHA (Total 3 drugs)

#
If still HbA1c >7% despite using 3 OHA (9 month)
#

It is Drug Resistant DM Treat with Insulin.

• Note : Metformin taken with or after meal to avoid Hypoglycemia.
• Fulminant DM : Very severe DM due to destruction of Beta-cell after Infection
(mostly viral).

2 Phenomena In DM

DAWN(down) SOMOGYI (So much insulin)

Low Insulin Patient increase take Insulin in Night

# "
Early morning hyperglycemia Hypoglycemia
"
Glucagon, GH, catecholamines & etc.
"
Early morning
"
Hyperglycemia

• HYPOGLYCEMIA occur in DM due to "Drugdose/ Insulin or miss meal.

• Hypoglycemia <70mg%
- It cause!!symptoms: Danger sign and symptoms of Hypoglycemia.
Like Headache, palpitation, sweeting, tremors etc.
- Advice ! Eat something (biscuit , cookie].
- Risk! Hypoglycemic coma.
- Treatment : IV 25% Dextrose./ 10% Dextrose.
COMPLICATION OF DM:

1. DKA (Diabetic Ketoacidosis)

• DM-I & uncontrolled DM.
• It is precipitated by Infections, Stress.
• Mainly "" inlevelofGlucagon,cortisol,catecholamine cause severe
hyperglycemic . B.sugar >250mg%

Increase Ketoacids : levels in blood & urine (Dipstick +ve)

#
(Acetone, Acetoacitic acid)
#
Cause :
• HGMA (high Anion gap met. Acidosis) PM27.35.
• Low Hco3 Acidosis Trigger Hyperventilation (co2 washout) Rapid, Deep
breathing called as KUSSMAUL BREATHING (air Hunger).
• Also Acetone cause SWEET FRUTY BREATH SMELL .

Clinical Features :

• Severe Dehydration
• low BP.
• "HR.
• Nausea,Vomiting, Abdominal Pain,
• #S.Na.
• "K
• Patient might be unconscious.
• Delirium,coma etc.
 Treatment :
¥ 1st give ßuid replacement (can put 2 IV lines)(6-8L needed).
• Start with NS (normal saline)
• IV Regular Insulin : 0.1unit/hr/kg.
Ex- 60kg = 6 unit/hr
• Monitor : K+, BP, PH, Glucose level.
• If hypokalemia : Add K+.

2 . Diabetic Retinopathy

• Earliest sign : Micro aneurysm.

• "VEGF (Neovascularization of Retina)

3 . Diabetic Nephropathy

• MC / cause of CKD & CRF

• Earliest: Micro albuminuria upto 299 mg/day.
• Hallmark ! Kimmelstiel/ Nodular Glomerulo Sclerosis. with hyaline
changes.
Rx : DOC - ACE-I/ARB
4 . Poor immunity and Poor Wound healing

• "Infections: Candida Albicans, mucormycosis.

• CARBUNCLE : Black lesion with hair follicles Infected. (multiple)
- M/C: Neck(back), Axilla, Shoulder back.
• Malignant otitis externa.
DIABETIC FOOT :

WET Gangrene

1. Ischemia (Coagulative Necrosis).

2. Infection (Liquefactive Necrosis).

5. Diabetic Neuropathy

• Autonomic.
• Impotence.
• Erectile dysfunction.
• Postural HTN
Peripheral Neuropathy
• 1st loss: vibration Glove & stocking sensory loss
• Stomping Gail
#
Damage to join Called as CHARCOT JOINTS.
Neuropathy Treatment :
• Pregabalin/Gabapentin.

6. Angiopathies

• Microangiopathy
• Macroangiopathy.

7. Thrombo Embolism
• Increase Risk of CAD , Stroke.
 THYROID
• Thyroid contain follicle & Para follicular cells.
• C-cells make calcitonin (" Bone Resorption).
• Follicles make Thyroid Hormone (T4 & T3)
• T3 is 5 times more active but T4 is produced more & long t1/2 6-7day That is we
use Thyroxine(T4) for the Rx of Hypothyroidism.
• In Myxoedema coma(T3) called as LIO thyroxine Enzyme needed to make
T3,T4 is : TPO(thyroid peroxidase) & Peripheral tissue T4 is converted to T3 by
5' Deiodase.
• ATD(Anti thyroid drugs) Rx for Hyperthyroidism.

• TPO" : Carbimezole & Methimazole

Prodrug Active metabolite
• More potent & longer acting. (main drugs for hyperthyroidism)

5' DeIodinase" : PTU (Propyl thiouracil)

"
Doesn't cross placenta

• Also in thyroid Strom$Doc!of hyperthyroidism in 1st trim of

Pregnancy.

Thyroid Hormone (Act by nuclear Receptor)

"
! Transcription

• "MRNA & "Protein formation : Brain & Body development in Early life
Hypothyroid children : Cretinism.
• LowIQ.
• Short structure.
• Infantile appearance (Bighead).

Increase Thyroid Hormones :

• "Beta-Adrenergic Receptor : "Sympathetic Activity.
• "Na+K+pump : "Activity of Brain (neurons) Heart GIT, kidneys etc.

Since body Activity level!!. It need more energy: !ATP consumption !BMR
#
[Normal 37-42 Kcal/hr/m2]
 Thyroid Regulation

Tertiary Hypothalamus
" TRH "
Secondary Ant. PITUTARY
" TSH " Negative feedback.
Primary Thyroid

!T3 !T4

TSN 1/! T3,4

• TSM Assay is best indicator of Thyroid Activity in TFT(Thyroid function Test).

• Normal TSH level! 0.55mu/L
• In cases of thyroid disorder will show opposite TSM change.
• 1°Hyperthyroidism: #TSH<0.5.
• 1°Hypothyroidism: "TSH>5.
• Euthyroid : Normal Thyroid activity.
• If TSH abnormal butT3,T4 normal & no sign and symptoms it is called as
subclinical Hypo/ hyperthyroidism.
• PIT Disorder cause secondary Hypo/ Hyperthyroid. NOW TSH & T4 in same
direction.
• Thyroid Disease cause Primary Hypo/Hyperthyroid. TSH & T4 in Opposite
direction.
TSH T4 Diagnosis Example

! ! Secondary Hyperthyroidism. Pituitary Adenoma Tumor.

" ! Primary hyperthyroid. Graves’ disease, Toxic Adenoma.

" " Secondary Hypothyroid. Pituitary lesion (Sheehan syndrome).

! " Primary Hypothyroid. Thyroiditis , Iron deÞciency Goitre.

• T3 normal : 1-8 ng/ml.

• T4 normal : 8-l0 µg/dL.

RAIU (Radio Active Iodine Uptake).

• It show thyroid activity on the basis of Iodine uptake by follicles.

• Isotopes used :
- I123 : for Diagnosis
- I131 : Ablation and Treatment.
- Tc99 : Technetium 99.
• RAIU! Black dots! Active follicle
• ColdNodule : #Activity.
• Hot Nodule : "Activity.
 GRAVE'S DISEASE

• PrimaryHyperthyroidism, "T3,4& #TSM

• B/L Diffuse enlarged Gland (Goitre) very vascular, Hot to palpable.

Pathophysiology :

• Autoimmune Disease
• HLA : B-8 & DR-3.
• Antibody Against TSH receptor called as LATS (long acting thyroid stimulation)

LATS
# ! Gland size & Activity.
"TSH ReceptorActivity
! T3,T4 levels.

• Type II & V : HS reaction.

• V>>II.

Clinical feature :
TRIAD.
1. Thyrotoxicosis : ("syrup, "BMR).
2. Dermopathy : Pre tibial mixedema d/t Hyaluronic acid deposition (Reddish
Brown plaque)
3. Ophthalmology : Proptosis, ophthalmoplegia, Exophthalmus, chemosis etc.
KOCHER SIGN : Staring look.

Lid Lag : Von Graefe sign.

lid retraction : Dalrymple.
Diagnosis :
• TFT.
¥ Clinical Þndings.
• LATS.

Treatment :
1. Younger Patient < 45hrs.
• Anti - Thyroid Drug.
2. Older Patient > 45years.
• Sx - Mills operation : sub total thyroidectomy or Radio ablation with
I-131.

THYROID STORM

• Excessive "" Thyroid Release.

- Ex: surgery cause thyroid storm.
• It cause Arrhythmia, Heart failure, Hemorrhage, stroke etc.
• Rx : IV Propranolol + PTU
- Can Add steroid (IV Hydrocortisone).

HYPOTHYROIDISM
• Primary
• T3,4 & "TSH.
¥ M/C Cause: Thyroiditis, Iodine deÞciency! Not Common in India Now.
¥ Goitrogenic food: Ex - mustard, caulißower, Broccoli.
• Drugs : Ex Amiodarone : Contain Iodine.

Wolff cheikoff Effect

Iodine # "T3,T4.
Ex : Lugol Iodine.
 Jod Basedow effect
Iodine # !T3,T4. Iodine Induced Thyrotoxicosis.

THYROIDITIS

1. Hashimoto Thyroiditis
• MC Hypothyroidism.
• f>M,Autoimmune, TypeII HS.
• HLA DR- 3,5
• Anti-TPO, Anti-TG Ab.
¥ Damage gland, WBC InÞltration.
• Hallmark : Hurthle cell
Pathophysiology :

Initially Leakage of T3,T4 cause :!Activity called as : Hashitoxicosis.

#
Gland destruction
#
Life long Hypothyroidism.
• Rx of Hashitoxicosis : PTU, B"
DOC ! Levothyroxine:1.6µgm/kg/day.
Ex: 100kg=160µgm/day.

2. SUB-ACUTE/ DE-QUERVAIN THYROIDITIS :

• 1st viral Infection (fever, pain etc)

#
Initially hyperthyroid (leakage), then Hypothyroidism (Destruction), Þnally
Euthyroid (Recovery).
Rx # Good prognosis, most Patient recover completely NSAIDs of
Hypo/Hyperthyroidism.

3. REIDELS THYROIDITIS
Idiopathic Þbrosis of Gland

Less gland Activity only Hard & Compress

hypothyroidism. Oesophagus & Trachea
#
Dysphagia, Hoarseness of voice.

Rx # Levothyroxine.
 ADRENAL GLAND
Present in upper pole of kidney

CORTEX MEDULLA
- steroids - catecholamines

• Catecholamines : Epinephrine, NorEpinephrine, Dopamine.

• Normal : E >> NE.

• Alpha 1 = "BP
• Beta1= !Heart "BP
• Alpha2= #sym #BP
• Beta 2 = #BP
• Epinephrine: Act on Alpha 1, Alpha 2, Beta 1, Beta 2= "BP.
• NE : Act on 3receptor : Alpha1, Alpha2, Beta1 = """BP.

• Liver Metabolite E,NE & Excreted in urine as:

- VMA : Vanillyl Mendeleic Acid.
- Metanephrine.
 PHEOCHROMOCYTOMA
• Tumor of chromatin cells. - It follow: 10 % Rule.
• 10% are B/L
• 10% are malignant
• 10% are extra Adrenal.
#
Extra Adrenal M/C site is Near Inferior Mesenteric Artery called as :
ORGAN OF ZUCKERKANDL.

• 10% Familial Ex : Part of MENZA (multiple endocrine Neoplasia).

Pathophysiology :

• Cells make more NE than epinephrine via Alpha-1 & Beta-1 cause ""sympathetic
and "" Blood pressure.

Rx # Alpha-1 blocker: Phentolamine, Phenoxybenzamine.

• Alpha-1 + Beta-1 blocker: Labetalol.
• Beta - blocker alone are Contraindicated.
Clinical features :
Triad.
1. Headache mc
2. " Sweating.
3. Palpitation due to " HR.

Hypertension : Episodic / Sustained.

!
cause Pressure Diuresis: "Urine output Intravascular Volume depression.

DIURETICS : are C/I : as most Patients are already dehydrated.

• Paradoxical / Postural Hypotension: On standing, dizziness & can fell down.
• Abdominal Pain, Nausea, Vomiting etc.

Investigation :
• Screening Test 24hours urine meta nephrite >> VMA.
• ConÞrmation : Plasma free metanephrine level, Also " Catecholamines.
• MRI/CT : for location, size, V/L or B/L etc.

• Also for metastasis: PET / MIBG scan.

 Treatment :
• Surgical Resection but 1st start with alpha-1 blocker.
• before Sx: oral Phenoxybenzemine.
• In 0T/ Intra OP ! IV Phentolamine.
• Post Operative : Labetalol.
• Pheochromocytoma - spillage of cate during Sx. "" Symp Arrhythmia, Heart
failure, Pal. odema etc.
• DOC ! IV Phentolamine + Labetalol.
# then
IV Nitroprusside

CARCINOID TUMOR

¥ Tumor cells : EnterochromafÞn cells origin of carcinoid Tumour.

• Neuroendocrine Tumor
• Mostly make 5 HT (serotonin)
• M/C site : Appendix, Ileum, Jejunum etc.

Clinical features :
• Flushing by PGE , bradykinin, histamine etc.
• Abdomen Cramping
• Diarrhoea
• Wheezing dlt Bronchoconstriction.
¥ Niacin deÞciency : Pellegra.
• Valvular lesion.
Diagnosis :
• " Metabolites called as : 5-Hydroxy Indole Acetic Acid. (5HIAA) "
5HT(serotonin)
Rx : Surgical Resection.
 ADRENAL CORTEX
• Make steroids

1. Zona Glomerular :

• Make Aldosterone : Stimulate P-cells of kidney (CD).

- via ENaC (Epithelial Na+ channel) : " Na+ Reabsorption & "Secretion of
H+, K+ "S.Na+ , # S.K+ ! Metabolic Alkalosis.
• Low Na+, High K+, RAAS ( Renin AT, Aldosterone system).
#
(Activate Aldosterone Release)

2. Zona Fasciculata :

• Make corticosteroids (Cortisol & Corticosterone).

• Use 11-Beta Hydroxylase 17,21 Hydroxylase.

3. Zona Reticularis :
• DHEA (DiHydroEpiAndrosteindione).

Aldosterone

Testing Leydying cell The Ca cells of ovaries

Aromatase

Testosterone Estrogen
Adipose Tissue

5AlphaReductase : # Prostate.

• 2 DHT: most active form.

5 alpha Reductase" by
• FINESTRIDE used for Rx of BPH & Androgenic Alopecia (Male Pattern).

Stress : Any threat to life / Homeostasis

#
Hypothalamus CRM "
# cortisol (steroid)
Ant pit ACTH " Inhibit HPA (Hypothalamus Pt. Axis).
#
Adrenal cortex cortisol

• Exogenous steroids suppress HPA & # Adrenal activity.

• Sudden withdrawal of steroids cause Addisonian crisis.

Action of cortisol :

1. Hyperglycemia.
2. Lipolysis & fat deposition Abdomen
back of neck.
3. Protein breakdown: Thin skin, muscle wasting.
4. Salt & Water Retention (Aldosterone activity).
5. " Catecholamines Action by : " Beta-Adr.Receptor: Hence without cortisol
The E, NE fail to act called as PermissiveAction.
6. Anti inßammatory & Anti allergic : • " TGF- alpha.
• " Histamine release.
• Diurnal rhythm of ACTH & Cortisol.
• Variation in Secretion during day.

• Maximum Stress in morning.

CUSHING SYNDROME

• Increase Cortisol level.

• M/C cause: Iatrogenic/ Exogenous steroids. " Cortisol
• Other : Adrenal Adenoma/ Hyperplasia. #ACTH

Cushing Disease
• Less common.
• Occur due to Pituitary Adenoma : "ACTH : "cortisol Both ACTH & cortisol High.
• ACTH via monocytes:"Melanin cause Dark pigmentation called as Acanthosis
Nigricans. (at Axilla , Neck )
Clinical features :

1. Earliest change is loss of Diurnal Rhythm.

2. M/C is obesity ! centripetal, pendulous Abdomen, Buffalo/ Camel humph Back.
3. Thin skin, Easily Bruising occur obesity: striae formed d/t stretching.
White or Red/Purple Striae ("RBC).
4. Muscle wasting: very thin limbs (sticks)
5. Osteoporosis: Fish mouth vertebrae (CodÞsh).
6. Salt & water Retention: facial oedema (Moon face/ Lunar facies).
7. Increase RBC : Polycythemia (Apple red cheeks).
8. Hyperglycemia.
9. HTN("Na+, #K+)
10. Decrease Immunity (Candida,mucormycosis) & Poor wound healing.
11. Decrease libido, Hirsutism, Ovulation failure("LH,FSH) : oligomenorrhoea.
12. Psychosis, mood changes,etc.

LEMON ON STICKS APPEARANCE

 Investigation :
• Screening Test: 24 hr urine cortisol level (>3 times the Normal).
• IOC : Dexamethasone suppression Test.
#

- Given in Night & Check 8am Serum cortisol.

- If High >50 mmol/L # ConÞrm Cushing Syndrome.
#
Check ACTH levels

Low High

Cushing Syndrome. Cushing Disease.

• Take history of Steroid uses. • Pituitary Adenoma or Para
• #CT/ MRI(Abd) forAdrenal Neoplastic syndrome Making
Adenoma / Hyperplasia. ACTH.
• Adenoma:U/L. • Ex : Lung cancers.
• Hyperplasia : B/L.

Treatment :

1. If due to steroid use Do not stop Abruptly (can cause Addisonian crisis) !
Gradually Taper the Dose.
Ex- 60mg!50!40!30mg or 3time!2!once a day/Alternative Day.

2. If Adrenal Adenoma! Surgical Resection.

3. Very Rarely use! Anti steroidal drugs & I.V. Aminoglulelhimide (#cortisol)
Ketoconazole , mitotane, metapyrone etc.
4. If Pituitary Adenoma# Cabergoline / Bromocriptne : Trans sphenoidal Resection.

CONN'S SYNDROME
• M/C cause : B/L Adrenal Hyperplasia.
• Others cause : Adrenal Adenoma / Carcinoma.
- Para neoplastic syndrome.
- High Renin levels.

Clinical features :

• Hypernatremia ("S.Na+>145mEg/L).
• Hypertension.
• NO oedema despite high Aldosterone.
- Called as : Aldosterone Escape due to "ANP.
• Metabolic Alkalosis due to high Acid secretion in Urine.
• Hypokalaemia #S.K+ <2.8mEq/L (equal to3) (ßaccid paralysis).
# cause
Muscle Wasting and Weakness.
• ECG changes! "PR interval, small T-waves.
Investigation :

• Screening by Aldo/Renin Ratio (>750)

¥ ConÞrmation by : Salt loading / Saline Infusion Test.
#
(Check S.Na+)
• CT / MRI Abdomen: Adrenal Hyperplasia / Adenoma.

Treatment :
• Aldosterone Antagonist or K+ sparing diuretics.
• DOC! Spironolactone & Eptevenone.
# (DiscoDrug) NO Gynecomesia
S/E# Gynecomastia

• If Adenoma : Surgery.
 ADDISON'S DISEASE : # Cortisol

2 Types :

1. Primary
• Adrenals making : Less steroids.
¥ Adrenal InsufÞciency.
• #cortisol, "ACTH

2. Secondary
• Pituitary Lesion.
• Decrease ACTH director.
• Decrease Low Cortisol.

1° Addison Disease:
• Cause : India M/C cause TB.
• World/developed countries ! Autoimmune.
Eg : Antibody against 21 Hydroxylase Infection of
Neisseria Cause Adrenal Haemorrhage.
• Cause Addison’s Crisis Called as : Waterhouse and Friedrichsen
# Syndrome.
Also, by sudden withdraw of steroids

ADRENAL INSUFFICIENCY

• less cortisol (opp of cushing syn. )

• Less Aldosterone
• Less sex steroids (DHEA, Testes, Estrogen)
#
Reproductive failure.
Clinical features :
• Hyponatremia : # S. Na+ <125mEq/L (Salt losing polyuria) Intense salt
Craving.
• Hypotension, Hypoglycaemia.
• Fainting, Dizziness, weakness etc.
• Poor stress Response.
• Weight loss.
• Abd pain, Nausea, vomiting etc.
• Metabolic Acidosis called as RTA-IV)
• Hyperkalemia "S.K+>5.5mEq/L
#
- Spastic Paralysis.
- ECG changes: Tall T-waves, ST-elevation.
! PR Interval, Arrhythmia,sine wave pattern (very high K+).
Investigation :
• IOC ACTH stimulationTest.

Treatment :
• DOC! HYDROCORTISONE 15-30mg/day in 2-3Doses.
Also Add DHEA.

Addisonian crisis:
• IV Hydrocortisone + Fluids (NS).
• IV Dextrose in Addison's Disease can use Glucose fever.

SUMMARY

"Na+ , K+ ! NO obesity, No oedma , Lemon on stick appearance.

"Na+ , K+ ! Odema, lemon on stick , obesity : Diagnosis: Cushing.

If #Na+, "K+ , #BP , #Glucose! Diagnosis: Addison’s Disease.

 PARATHYROID GLAND
• At Inferior Part of Thyroid, 4 in number.

PTH ! Increased by : #S.Ca, S.PO4, #S.Mg2+.

#
!Osteoclast: !BoneResorption,Alsovia# Vitamin-D Cause : !ca+ from GIT & kidney.

• PTH ""S.Ca2+ but # S.PO4 (Renal excrete).

• Normal S.Ca2+ : 9-11mg%.

3 Types of Hyperparathyroidism.

1. Primary
• Parathyroid adenoma/ hyperplasia. "PTH = " Ca2+ & # P04.

2. Secondary
¥ Low S.Ca2+ (Vit-D deÞciency, Renal Defect).
#
! PTH
3. Tertiary
• Chronic Sec. cause : "Ca2+ (Not as High as Primary).

Clinical features :
• Stones, moans , Groans, Bones.
• Abdominal Pains, Nausea, Vomiting : Cousin Groans.
• Psychic moans.
• Hypercalcemia : "S.Ca2+ >11mg%
• " Stone formation, ECG Changes (#QTcInterval) Hypertension, Arrhythmia.

Bone : Sub-Periostal Resorption.

#
Lacunae, Fluid form cyst later Þbrosis Called as Brown Tumor.

OsteitisÞbrosa Cystica
Rugger Jersey Spine.

Salt & Pepper skull due to : Lacunae (Black)

• Punched out lesions in multiple myeloma

Treatment :
• loop Diuretics: to correct Hypercalcemia
• # PTH by Cinalcet
• Teriparatide: "osteoclast
• Bisphosphonates :" Bone Resorption.
 HYPOPARATHYROIDISM

• Most common cause : Autoimmune Disease/ Destroy Parathyroid gland or

Post thyroid Surgery

Clinical features :
• Hypocalcemia Tetany #S.Ca2 <9mg%.

1. Trousseau Sign : Carpopedal Spasm.

2. Chvostek Sign

Treatment :

• 10% Ca2+ Gluconate (SlowInfusion=10mL in10minute).

Treatment :
• Cebergoline / Bromocriptine.
#
Trans spheroidal Resection of Pit Adenoma.
3 NEUROLOGY

HEADACHE and MIGRAINE

• Headache occur due to Irritation or Inßammation of Duramatter.

• Pain sensitive part also known as : Cephalgia.

There are 2 Types of headache :

1. Primary Headache
• Headache is a disease.

2. Secondary Headache
• It occur due to another cause like : Trauma, Meningitis, SDH, EDH, etc.

Types of Primary Headache:

1. Tension Headache
• Most commin primary headache  Bilateral
• Female>male
• Band like compression
• Feature less headache : No Nausea, No Vomiting.
• Short lasting
• Rx : NSAIDs.

2. Cluster Headache
• Male>female
• Unilateral headache
• H/O of cry
• Retro orbital severe and excruciating piercing pain and occurs in groups
or clusters of few seconds to minutes but never >3hrs.
 • Its periodic in nature, Occur same time.
• Also a part of trigeminat neuralgia, Also shows red eye, Increased tear
Secretion, Crying or Lacrimation known as Epiphora(autonomic features).
• Rx : Sumatriptan and high ßow Oxygen.
• Other drugs : Valproate, Gabapentin, Carbamazepine.
• Prophylaxis : CCB( verapamil)

3. Migraine

• Female>male
• Unilateral(half head)
• Triggers or Stimuli (Light or sound).
#
• Depolarising electrical activity.
#
• cGRP(calcitonin gene related peptide).
#
¥ Inßammatory changes,vasodilation
- hence migraine has vascular basis PULSATILE.
Diagnosis :
P : Pulsatile
O : One day duration ! 24h(4-72hr)
U : Unilateral.
N : Nausea, Vomiting.
D : Disability (can’t walk).
• Sensory disturbances before attack.
• Eg : Photopsia, Tingling, Scotoma
• This is known as AURA.
• If aura present : Classical migraine.
• >5attacks/year : Recurrent migraine.
• Pain worsening by movement, light, sound, stress etc.
• Patient has Photophobia, Phonophobia, Osmophobia.

Treatment :

• Mild to Moderate : NSAIDs.

• Moderate to Severe or when NSAIDs fails : Cause Vasoconstriction :
Triptans-5-HT1B and 5-HT1D Receptor agonist.
- Sumatriptan (Mostly used).
- Frovatriptan.
- Rizatriptan.
- Eletriptan
- Naratriptan.

• Earlier Ergot derivatives were used : Methyl Ergometrine (Methergine).

• Used in PPH as It cause Vasoconstriction.

• Side effect : Gangrene.
Prophylaxis :

• Beta blocker : Propranolol.

• Other drugs : Valproate (Most efÞcacious).
Topiramate (Preferred in obeisity).

• New drugs : Monoclonal Antibody agains cGRP.

Galcenezumab.
Frenuzumab.
• cGRP antagonists : gePant.
Eg : Rimegepant, Olcegepant.
 DEMENTIA

Loss of higher Cognitive function.

#
- Return to newborn state.
4A of Dementia :
• Amnesia : loss of memory.
• Aphasia : loss of speech.
• Agnosia : loss of knowledge(Agyaani).
• Apraxia : loss of motor movements (learned skills).

• Muscles are normal but brain can’t command them(just like newborns).
¥ Reßexes of respiration are normal
• Dementias are due to loss of Cortical Cholinergic Neurone.
• MCC : Old Age / Senile dementia.
• Not pathological,they can do normal activities and have a normal life.

Dementia Delirium
• No loss of consciousness till • Altered or loss of Consciousness.
the end.

Reversible Dementia
¥ Vitamin deÞciency.
Eg : B1(Beri Beri)
• Hypothyroidism
• Normal pressure hydrocephalus
• Alcoholics : B1 thiamine DeÞciency.
• Earliest in alcoholics : Tremors(Delirium Termor).
 Wernicke encephalopathy
• G : Global.
• O : Ophthalmoplegia confusion.
• A : Ataxia.

• Korsakoff Psychosis : False memory known as Confabulation

Rx : For all types -Vitamin B1.
- IV in Delirium

Irreversible Dementia

• Alzhimer’s disease
• Lewy body dementia (Parkinson with dementia)
• Vascular dementia (Multiple infarcts)
• Huntington disease(decreased Ach,increased dopamine).
• Prion disease : abnormally folded proteins.
- Normally Prions are Alpha-helic, After infection it becomes Beta-Pleated
Sheets(scrapie prion sheets).They accumulate and damage neurons. i.e,
Spongiform encephalopathy.

Transformation of Alpha helic to Beta

 Spongiform Encephalopathy

Rapidly Progressive Severe Dementia.

• Death within 6 - 12 months.

• No effective treatment
• Most patients show myoclonic jerks(90%)
• Infection can be due to iatrogenic,infected meat,organ transplant(even cornea).
• Can be genetic.
Eg : Fatal Familial Insomnia.
¥ No fever, No Inßammation.

ECG : Sharp periodic atrophy.

MRI Findings
• Gross cortical
• Enlarged ventricles
• Cortical ribboning
• Pulviner, Hockey stick sign.

Hockey stick sign

 PRION DISEASE
Eg :
• Mad cow disease/ Bovine spongiform encephalopathy.
• Due to beef : not in india.
• Kuru disease : Cannibals:eat other humans
• Fatal familial insomnia : Genetic (history not sleeping).
• Creutzfeldt-Jakob disease : MC variant of prion disease in India.

ALZHIMERS DISEASE
• MCC of Dementia in Elderly >65 years : Pre senile dementia
• Strong Genetic basis : High risk in down syndrome(trisomy 21).
• Presenillin : 1 & 2 gene
- APOE2 : Protective, Low risk.
- APOE4 : Causative, high risk.

Pathophysiology :
• First and main : Destruction of Nucleus Basalis of Meynert.
• Meynert : Give Ach to entire cortex, there is loss of cholinergic neuron in
Alzheimer’s.
• Cortical and hippocampus atrophy : Memory loss.
• Hirano Bodies Present in : Hippocampus.

Two main Proteins :

1. Tau Proteins :
• They help microtubules in neurons but increased Tau protein aggregation
causes NeuroÞbrillary tangles inside the neuron and damage neurons.
 2. Amyloid Precursor Proteins(AAP)
# alpha,beta-gamma Secretase.
A beta-amyloid oligomer
#
Polymer and accumulate outside as senile/ Neuritic Plaques.

Clinical features :
• 4 A of dementia.
• Earliest-episodic memory loss
• Loss of Visuo Spatial Skills, Agraphia, Acalculia, Aprexia, Agnosia.
• Severity increase : Can’t recognize relative(Family Support)
• Myoclonic jerks
• Capgras/Fregoli delusion.
¥ Newborn reßex reappear and rooting ,sucking.
Investigation :
• Mini mental state examination-<24 score out of 30 in dementia.
• MRI : Gross cortical and hippocampus atrophy, Enlarged ventricles, Thin
gyrus and Deep sulcus.

Treatment :
• Supportive care
• Increase Ach by cholinesterase Inhibitor.
• DOC : Donepezil.
• Other drugs : Tacrine(Hepatotoxic) , Galentamine, Rivastigmine.
• New drug : Memantine : NMDA antagonist and Decrease glutamate toxicity
 BASAL GANGLIA
• Around thalamus.
• Parts : Caudate nucleus.

• Internal capsule : Present between thalamus and lentiform nucleus.

• Corticospinal/ Pyramidal tract pass through Internal Capsule.

Functions of basal ganglia :

• Planning and programming of movement

• Increased movement(pyramidal tract) and muscle tone(extrapyramidal tract).
• All structures and neurotransmitters reduce movement(LN,CN,STN)
• Only dopamine from Substantia Nigra.
• Pars compacta-increase movements and control tone.
• So,lesion in Substantia Nigra decreases Dopamine: Reduce movement, Rigidity
(Decrease Tone), Resting Tremors.
• Known as Parkinsonism, Shaking Palsy.
Lesion in other areas :

• Caudate nucleus lesion(GABA) : Chorea, Involuntary dancing movement.

• Lentiform nucleus lesion(GABA) : Athetosis; Involuntary twisting of wrist
• Subthalamic nucleus lesion(Glutamate) : Hemiballismus;Violent throwing or
failing mivement of arm(involuntary).
• Huntington disease/ Chorea-Striatum lesion (Both Caudate nucleus + Putamen).
- Loss of GABArgic neurons of striatum.
- Low GABA, low Ach and high dopamine : Increased movements(chorea).
• Autosomal dominant. Chromosome 4-Huntington gene.
• Trinucleotide repeat CAG repeats.

Clinical features :
• Low Ach : Dementia
• High dopamine : Psychosis, Violent, Aggressive behaviour, Dystonia,
Hyperkinesis, Chorea.
Treatment :
• Tetrabenazine, Valbenazine : Inhibit dopamine release.
• Also used in Tardive dyskinesia.
 PARKINSONISM

• It is Progressive disorder that affects the nervous system and the parts of the body
controlled by nerve.

Pathophysiology :
• Low dopamine and high GABA,High Ach
• Opposite to huntington disease.

Cause :
• Drug induced parkinsonism
Eg : Tetrabenazine/ Valbenazine /Anti psychotics,heroin metabolites.
• Trauma : especially boxer
Eg : Mohammed Ali
• Infections
• Metabolic disorder : Wilson’s disease.
- Autosomal recessive chromosome-13.
- Defect in ATP7B gene,hence decreased ceruloplasmin which bind
and transport copper, lead to increase in Copper levels which get
deposited and damages the liver- cirrhosis.
- Bronze pigmentation on skin
- Sunßower cataract and KF ring on eye.
- Basal ganglia ! lenticular degenration= Parkinsonism
Diagnosis : Wilson’s disease
• Licer, Copper levels,Ceruloplasmin levels.

Treatment : Wilson’s disease

• EDTA,Chelate copper

MENKE’S DISEASE
• ATP 7A gene defect.
• X linked recessive.
• Abnormal white matter.
• Severe Atrophy of cortex.
• Kinky hair, low serum copper,low ceruloplasmin Not a cause of Parkinsonism.
 PARKINSON’S DISEASE
• Diagnosis by excluding other causes mostly elderly patients.

Diagnosis :

• Degenrarion of substantia nigra.

• Dopaminergic neurons lowers dopamine and increases Ach.
• Due to deposition of alpha-synuclein protein(synucleopathies).
• They make intracytoplasmic inclusion bodies known as Lewy bodies.

• If Dementia with Parkinsonism : Lewy body Dementia.

• In parkinson disease,less or no dementia with presentations of Parkinsonism.

Clinical features :

1. Resting tremors

• Frequency 4-6Hz. Fine Tremors, mostly hands,assymetrical(one sided)

Eg : Pin rolling Tremors.
• Tremors reduce during movement.
2. Rigidity

¥ Increased muscle tone, muscles of ßexor and extensor group High resistance
felt when trying to move and feeling like Bent lead Pipe.
• Cogwheel Rigidity : Resistanse is not uniform,on and off, series of catches and
jerks.

3. Reduced movement
• Dyskinesia
¥ Initially difÞcult in staring movements
• Hypokinesia and bradykinesia-Small and slow movements.
• Micrographia-small handwriting
• Reduce blinking,arm swing,walk with small steps etc..
• Mask like face-Hupomimia(reduced facial expressions).
• Freezing episodes, Akinesia(statue like).
4. Autonomic dysfunction
• Bowel/ bladder control is poor
• Postural hypotension
• Impotence.
5. Posture and gait disturbances
• history of falls.
¥ Festinating/shufßing gait-small steps,alternate
• steps with narrow base, Stooping forward.
Treatment :

• Goal is to lower Ach and increase Dopamine.

1. Amantidine : Used for inßuenza Rx but also increases Dopamine release

from vesicles
2. LevoDopa : Cross BBB and converted to DA.
3. Carbidopa : Inhibit decarboxy peripheral breakdown of l-Dopa(increase
L-Dopa) Benz-anticholinergic:other act via Dopamine
Benztropine,benzhexol,promethazine(DOC)
4. Dopamine agonist : Directly act on D1-Receptor
- Ropinarole (DOC : Parkinsonism and restless leg syndrome),Pramipexole.
5. Geline : MAO-B inhibitor : Increase DA by preventing breakdown Rasageline,
Selegeline.
• SaÞnamide : DOC for on/off phenomenon.

Note :- COMT inhibitor eg : Entacapone, Tolcapone.

• On off phenomenon : when we give L-Dopa it get stored in neuron and can
work upto 24hours.
• In late parkinsonism,all storage capacity has been run off and the dopamine
works only for 24hrs. Drug is working ON but over working. Drug is not
working OFF in Parkinsonism.

Management Protocol :
• Young Patient-Ropinirole stimulates MAO receptor or inhibit COMT
• Older patient >50 years : L-Dopa + Carbidopa.
• S/E : After years of use, patient develops on/off phenomenon.
• DOC : SaliÞnamide.
• Surgical Management : Deep brain stimulation + basal ganglia via electrodes.
 Atypical Parkinsonism Typical Parkinsonism

• Less tremor • More tremors.

• Poor response to L-Dopa. • Good response to L-Dopa.
• Involve other brain parts also • Mainly RRR
So, other Signs and symptoms seen. Eg : Parkinson disease
Wilson disease,DIP.

Atypical Parkinsonism
1. Progressive supranuclear Palsy.
Lesion of medial longitudinal Fasciculus.
#
Supply extra ocular muscle
#
Affect mainly downward gaze,cant climb down MRI : Humming bird sign

EOG : Record eye movements

#
Square wave pattern seen.
2. Multisystem Atrophy
• Shy dragger syndrome.
• Involves basal ganglia, Cerebellum, ANS etc…
• Features : Parkinsonism, Ataxia, Autonomic dysfunction.

3. Corticobasal degeneration
• Atrophy of cortex and basal ganglia.
 CEREBELLUM

• Floculonodular lobe/vestibulo cerebellum : For gait and movement.

• Cerebellar hemisphere/ Neocerebellum also known as Cerebro cerebellum.
- Function : Correction and coordination of movements.

Deep cerebellar nucleus : 4 in number

1. Dentate nucleus.
2. Emboliform nucleus.
3. Globose nucleus.
4. Fastigial nucleus.
5 Types of neurons :
1. Granule cells (glutamate).
2. Purkinje cells (main output).
3. Golgi cells
4. Basket cells.
5. Stellate cells/neurons.

Cerebellar functions and lesions.

• Control Tone, Posture, Balance, Gait, Gaze(eye movement by vestibulo ocular
muscles).
• Motor leaening like : Driving, Swimming. It is a type of imlicit memory (can’t be
recalled consciously).
• Correction and coordination of movement.

Lesions of cerebellum
¥ Ipsilateral hypotonia/ßaccidity(decreased tone).
• Intentional tremors : Appear on movements and increased error during
Task, Jerky movements.
• Incoordination (loss of coordination) known as Ataxia.

Tests for coordination

• Ataxic/ Drunken gait : Patient cant stand,walking zig-zag (It is called drunken
gait because alcohol also depresses cerebellum if alcohol level is >150mg%)
• Slurred speech : Dysarthria.
• Nystagmus : Oscillation of eye ball.
¥ Past Pointing in Þnger Nose test.
• Dysdiadochokinesis : Unable to do rapid alternative movements.
Friedrich’s Ataxia
• Frataxin gene defect, chromosome 9.
• Degeneration of spinal cord neurons and decreased cerebellar connections
causing ataxia.
• Triple nucleotide repeat GAA.

Sensory Ataxia

• Normal cerebellum but can’t do coordination due to loss of sensory traits and
informations.
Eg : Tabes dorsalis.
• Romberg’s sign positive in sensory ataxia.
- Patient using vision for coordination so,on closing eye,patient falls down.
 MENINGITIS
¥ Inßammation of meninges.
Causative organism
BACTERIAL MENINGITIS
1. TB MENINGITIS :
¥ Maximum increase in proteins-makes white spider web like
coagulation known as : COBWEB FORMATION.

¥ Acid fast bacilli (red color rods).

¥ Increased lymphocytes : single
big nucleus.

COBWEB FORMATION

2. Pyogenic Bacterial meningitis

Pneumococcal Meningococcal

¥ Strep. Pneumonia ¥ Nesseria Meningitis.

¥ Gram +ve cocci in chains. ¥ In capsule, Kidney shaped gram
-ve diplococcus.
¥ Also presence of skin rash.

¥ In bacterial Meningitis(except TB meningitis) Main cells are neutrophils :

Polymorpho Nuclear (PMN).
¥ PMN is 2-6 lobed nucleus.
 Age MC organism
India
¥ Gram -ve : E.coli, Klebsiella
0-2 months ¥ Gram +ve : Staph.

World
¥ Gram +ve : Staph, Streptococcus.

2m-2year ¥ inßuenza , Meningococcal

>2yr ¥ Meningo>>pneumococcal

Adults ¥ Pneumo>>Meningococcal

Epidemic ¥ meningo>>Pneumococcal.

HIV +ve ¥ Cryptococcal neofromins (oppurtunistic

infections)or listeria Monocytogens.

VIRAL MENINGITIS
¥ Children-MC japanese encephalitis Seen in UP,bihar(chanki fever)
¥ Herpex simplex-I- DOC Acyclovir
¥ CMV- DOC- Ganciclovir

Clinical features :
¥ High grade fever,sign of meningeal involvement.
¥ Nausea, Projectile vomiting, headache.
¥ Neck rigidity/Nuchal rigidity.
2 signs
1. Kernig sign : Knee and leg canÕt be extended.
2. Brudzinskis sign : Neck ßexion cause knee ßexion
¥ Increased Intra cranial pressure : Papilloedema, Increased BP but low heart rate
(Cushing reßex).
¥ Seizures,decerebrate rigidity(all limbs extended)
¥ Coma.

Management :
¥ Start empirical treatment with IV ceftriaxone and Vancomycin.
• Lumbar puncture : for CSF exam
• Normal CSF : Clear looking, glucose : 60mg%.
¥ Protein : 15-45mg% ,cells absent.
¥ Fungi, Bacteria eat glucose(virus cant eat glucose).
¥ And also cause inßammation (Increased ICP >10mmHg).
¥ Increased cells : Lymphocytosis ; Color-Turbid & Cloudy TB and viral.
¥ Protiens : PMN : Bacterial/Pyogenic >1000 cells/cvmm).
CSF Normal Pyogenic TBM VIRAL FUNGI

COLOUR Clear. Turbid Straw Clear Cloudy

PRESSURE 10mmHg. Increase Increase Normal Increase

CELLS 0-4/mm3 Neutrophils Lymphocytes Lymphocytes …………

(>1000). (100-1000). (>25)

GLUCOSE 60% of plasma. Decrease Decrease Normal Decrease

PROTEIN 15-45mg%. Increase Maximum Normal Increase

increase
(>100mg%).

¥ NOTE : In viral meningitis everything is normal EXCEPT Lymphocytes (increase).

Treatment :
¥ DeÞnitive treatment after identiÞcation of organism.
¥ If Meningo/Pneumo : DOC Penicillin G but can continue Ceftriaxone.
¥ Gram -ve 3rd gen Cephalosporin : Ceftriaxone.
• Cryptococcal : DOC : Liposomal amphoterecin B + Flucytosine.

¥ NOTE : Liposomal Amphoterecin B also DOC for Deep systemic fungal infection.
Eg : Mucor mycosis.
Systemic candida.

• TB meningitis : ATT & steroids.

¥ Steroids : decreased inßammation and prevent adhesion between meninges.
 SEIZURE

¥ Paroxysmal(sudden)synchronized hyperactivity.

Cause :

¥ Vascular
¥ Infection
¥ Trauma/Tumours
¥ Autoimmune disorder.
¥ Metabolic disorder
¥ Idiopathic (mc in childrenÕs).
¥ Neurocysticercosis (uncooked beef/pork).

NEUROCYSTICERCOSIS
¥ Beef : T.Saginata.
¥ Pig : T.Solium.
¥ Larva can reach brain and form multiple cyst and get calciÞed.They
cause inßammation and irritation.
¥ CT/MRI head-multiple cyst (parasite inside cyst alive)
¥ Treatment
- Albendazole.
- Steroid
- Anti epileptics
¥ IOC : for seizures - EEG.
¥ If seizuee has muscle contractions, known
as Convulsions.
¥ If >2 seizure episodes known as Epilepsy.
Types of Seizures :
1. Subtle seizures
¥ MC in neonates due to incomplete myelinatiin,hypoxic ischemia
encephalopathy.
2. Febrile seizures/convulsions
¥ MC age is 6m to 5yrs.
¥ Episodes of fever : Generalised tonic clonic seizures.
¥ DOC : Rectal diazepam or IV lorazepam.
¥ Prophylaxis : Clobazepam.

3. Infantile spasm
¥ Age 1-2 years.
¥ Muscle goes into contraction spasm :
- Flexon : Jack and knife position
- Extensor
- Mixed : MC in india
• EEG : high voltage,irregular activity known as Hypsarrytymia.
• DOC : ACTH, Steroids.
4. Absence seizure/ Petitmal epilepsy
¥ Most commonly seen in school going children
Clinical features
¥ No classical Þnding like muscle contraction
¥ No loss of concsiousness,no feeling etc
¥ Blank staring episode of few seconds,child unresponsive
¥ Teacher complaints of day dreaming and not paying attention.
¥ If muscle involvement present it is known as atypical absence seizures.
• EEG : 3Hz wave and spike pattern(3 wave in 1 sec)
Treatment
¥ Typical : MC
- DOC : Ethosuximide>>Valproate.
¥ Atypical : Rare
- DOC : Valproate

5. Juvenile seizure
¥ Myoclonic jerks/ Seizures.
¥ No loss of concsiousness
¥ Group of muscle or half body start involuntary suddenly contract and
relax multiple times.
¥ Genetic basis,positive family history(clonus)
¥ Example of myoclonic is : JANZ SYNDROME.

6. Juvenile myoclonic epilepsy

¥ Seen in adolescents(10-19yrs)
¥ Related to sleep deprivation
¥ Occur in morning whike waking up Sudden Bilateral myoclonic jerks occurs.
• EEG : Polywave and spike(4-6Hz) or polyspike pattern.
¥ DOC : Valproate>>Lamotrigine
 Juvenile myoclonic epilepsy

7. Generalised Tonic Clonic Seizures

¥ All muscles involved
¥ M/C in young adults(17-18 yrs)
¥ Mostly due to cerebrovasculat disorder
¥ Also known as Grandmal epilepsy (Old child).
¥ Most patient start with GTCS suddenly,few have prodormal stage.
• 1st Loss of consciousness : Patient falls down
• 2nd tonic stage(10-20sec) all muscles goes into sustained contraction Teeth
clenched, Tongue bite,to prevent blood aspiration,turn patient sideways,
Bowel/Bladder emptying.
¥ 3rd clonic stage(1-5min)
- All muscles contract and relax multiple times.
- Alter seizures : Postictal phase(patient can remain unconcsious/sleep).
- Nausea,vomitting,headache,confusion,amnesia etc
¥ If GTCS continue >5min, known as Status Epilepticus.

Stages of Status Epilepticus :

¥ Early : 5-30 minutes.
¥ Established : 30-60minutes.
¥ Refractory : >60minutes.
Status epilepticus need immediate Treatment :
¥ IV lorazepam &IM Midazolam
#
¥ IV Phenobarbitone(C/I in Porphyria)
#
¥ Last option : Use GA(propofol)

• GTCS EEG : Burst suppression pattern, Low discharge then high voltage activity.

Treatment :
¥ DOC : Valproate (Atonic/Myoclonic/GTCS/ Atypical) Valproate is teratogenic
and cause neural tube defect.
¥ Female who want to be pregnant-Stop valproate. Use Levetiracetam,
Lamotrigine.
¥ Already pregnant : continue valproate and Add folic acid 4mg/day or
400microgrm/day.
Focal/ Partial seizures

¥ Affecting some part of cortex

¥ If loss of concsciousness press-complex partial otherwise,simple partial
- Eg: Temporal lobe epilepsy : sensory, memory, psychiatric disturbances.
#
- Auditory hallucinations
- Treatment-carbamazepine.
- Increased spiritiuality
- Delusions,behavioural changes
 UMN and LMN

Upper motor neuron lesion vs Lower motor neuron lesion

• UMN : CORTEX
Eg : Moter cortex (Benz cells).
• LMN : Motor neurons which give motor nerves.

Spinal nerves
¥ From anterior horn of spinal cord.
¥ Cervical, Thoracic,lumbar and sacral.
¥ If lower limbs paraplegia(loss of power)/paraperes is(reduced
power).

Cranial nerves
¥ Brain stem nuclei(bulbar)
- VII,IX,X,XI,XII
- Pharynx-IX,X
- Neck-XI
- Larynx-X
- Tongue-XII
¥ Bulbar palsy-Weakness/ paralysis of these muscles.

¥ If half body affected-Hemiparesis/plegir(mostly internal capsule lesion)

¥ Quadriplegia : 4limbs affected.
¥ UMN control LMN (tone,reßex&power)via motor descending tracts.
• Eg : Corticospinal tract : LMN In spinal cord.
Corticobulbar tract : LMN in brain stem.
¥ All Þbres pass via internal capsule and cross to opposite side at lower end of
medullary pyramids. Hence also known as Pyramidal tract.

1. For voluntary Þne skilled movement like writing,draing.

2. Also control the tone and posture
3. Produce plantar ßexions planter in reßex (downward movement of great toe).

If pyriamidal tract lesion :

¥ Loss of control tone
¥ Loss of voluntary movement on opposite side of body C/L hemiplegia.
¥ Loss of plantar reßex(no downward movement).
#
Dorsißexion of great toe known as extensor response.
- Positive Babinski sign.

Babinski sign.

SUMMARY

¥ Pyramidal tract lesion : UMN lesion

- As tract injured,it causes paralysis because UMN fail to
control LMN
Uncontrolled LMN cause :

¥ Increased muscle tone : Spasticity(contracted).

Eg : Clasp knife Spasticity.

- Examiner will Þnd high resistance.Also spastic/circumduction gait patient

cannot lift paralysed limb,so he drag it/sweep gait.

Pyramidal tract lesion

¥ below medulla. Eg: Spinal cord (ipsilateral spastic paralysis below lesion.
¥ Cerebral Palsy both side are damaged.

LMN lesion nerve lesion

¥ Anterior horn lesion Eg : Poliomyelitis.
¥ Spinomuscular atrophy
¥ Amylotophic lateral sclerosis(stephan hawking)
¥ Pyriamidal tract lesion present anterior horn lesion-UMN &LMN.
¥ Normal IQ,normal sensory,normal ocular movements. SOD gene
mutation : Superoxide dismutase
¥ Increased free radicals : Damage motor neurons(UMN &LMN).
 • Treatment : Riluzolec & Edaravone (anti oxidant) : Decreased
glutamate toxicity and supportive care, death due to respiratory
paralysis.
¥ Also neuromuscular disease and muscle disorder like Becker &
Duchenne muscular dystrophy are LMN lesion.

Becker & Duchenne muscular dystrophy

¥ Genetic defect in : Sarcolemmal dystrophin complex.

¥ Limb muscle affected
¥ DifÞculty standing/walking
¥ Use upper body and hands to stand up : Gower sign.
• LMN Lesion: from anterior horn/brain stem(motor neuron) to nerve,
neuromuscular junction or muscle LMN tail to stimulate muscle,so loss
of contractions: - Decreased tone : Flaccid paralysis.
- Reduced reßex : Areßexia/Hyporeßexia.
¥ Severe muscle wasting known as disuse atrophy.
¥ After regeneration(months) there is spontaneous contraction called as
Fibrillations and Fasciculations (Twitching).

Eg : Hypoglossal nerve injury : Bulbar palsy (LMN lesion).

¥ Wasting
¥ Speech difÞculty : Dysarthria due to muscle weakness.
¥ Flaccid paralysis.
¥ Tongue deviation on same side due to genioglossus muscle.
¥ Fasciculation in muscle
¥ Tongue Þbrillation only on EMG(electromyography)
¥ If ALS/motor neuron disease, bilateral wasting and fasciculation
Corticobulbar Tract injury : Stroke

¥ UMN lesion of bulbar muscle called as pseudo-bulbar palsy .

- Spastic paralysis.
- Less wasting.
- No fasciculation.
- Tongue deviation to opposite side.
SUMMARY
UMN LMN
¥ Tract lesion ¥ Nerve,NMJ,muscle lesion.
¥ Spastic lesion ¥ Flaccid Paralysis.
¥ Less/No wasting. ¥ Severe wasting.
¥ No fasciculation. ¥ Fasciculation.
¥ Increased deep tendon reßex ¥ decreased deep tendon reßex.
¥ Positive Babinski ¥ Negative Babinski
 STROKE

¥ Sudden, non convulsive focal neurological deÞcit(motor/sensorycognitive)

lasting>24hrs.
¥ If recovery within 24 hours known as Transient ischemic attack.
¥ If within 72hrs known as Reversible ischemic neurological deÞcit,or more
than 24hrs but recovery in 7 days.

• ABCD2 score : Risk of TIA progression into stroke.

1. Age >60 year : Score 1
2. BP >140/90 : Score 1
3. Clinical features :
- Speech difÞculty : Score 1.
- U/L body weakness: Score 2.
4. Duration:
¥ <60 minutes : Score 1.
¥ >60 minutes : Score 2.

5. DM Score : Score 1

• >7 score,more risk of stroke

Pathophysiology

¥ Decreased blood ßow.

#
Hypoxia
#
¥ Damage to neurons
(liquifactive necrosis)
- Cause neurological deÞcit.
Types of Stroke :

1. Ischemic Stroke :

Thrombotic Embolic

• MC : Atherosclerosis ¥ DVT, A.Fib, Infective Endocarditis,

of cerebral vessels Drugs, SLE, OCP.

2. Hemorrhagic Stroke :
¥ Young : MCC is Trauma.
¥ Adults : MCC is HTN.
¥ Putamen is the mc site of hypertensive bleeding.
¥ IOC for stroke : NCCT head.
¥ Ischemic : Bleeding/hemorrhagic.
¥ Infarct(black/dark) : hypointense,Hyperintense.
¥ MRI better than NCCT but time consuming and costly.
¥ Good standard : Cerebral angiography.
¥ Other : BP, Surgical level.
 Intracranial Haemorrhage

1. Extradural Haemorrhage
¥ Edli shaped (biconvex)
¥ MCC is trauma-head injury mostly young people MC vessel injured MMA
(middle meningeal artery)
Clinical features
¥ Lucid interval
¥ Ist loss of consciousness then Regain concsiousness.
¥ Headache,nausea,vomiting
¥ 2nd LOC (Dangerous,death occurs).
¥ IOC : NCCT head.
¥ Treatment : Craniotomy
- Immediate(hematoma extraction).
2. Subdural hematoma
¥ Under dura.
¥ Sickle or C-Shaped/Crescent shaped.
¥ Injury to cortical bridging veins.
¥ Similar to EDH, but no lucid interval.
¥ Treatment :

3. Sub arachnoid hemorrhage

¥ CSF present in subarachnoid space

¥ Hence SAH will cause blood in CSF in lumbar puncture.
¥ It cause branching/river pattern due to blood in sulci
¥ Causes : Trauma, Rupture of berry aneurysm
¥ Berry aneurysm : mc site circle of wills.
5 Branches of internal Carotid Artery

1. Anterior cerebellar artery

2. Ophthalmic artery.
3. Middle cerebellar Artery.
4. Anterior chorodial artery.
5. Posterior communicating artery.

Internal carotid Artery

¥ Anterior Communicating artery : Frontal lobe.
¥ Middle Communicating artery : Temporal lobe.
¥ Basilar artery-Posterior communicating artery : Occipital lobe.
¥ Circle of wills not having MCA but ACA,PCA and communicating
branches.
Clinical features :
¥ Blood in CSF acts as irritants.
¥ Meningeal involvement
¥ Neck rigidity
¥ Vomiting
¥ Thunder clap headache (worst headache of life).
¥ Hunt-hess grading scale is used to detect severity of the pain.

Treatment :
¥ Control BP to reduce bleeding.
¥ Target <140\90
• Drugs used : CCB, Nimodipine/Cleridipine
¥ Surgery : Aneurysm clipping and coiling.
Stroke With Hemiparesis.
¥ MC Vessel involved : (MCA) Middle communicating artery and branches
supplying internal capsule causing PT lesion. Known as Striate or Lenticulo
Striate branches. (Charcot Artery).

Management of stroke
¥ Find wether ischemic or hemorrhagic.
• If hemorrhagic : Lower down the BP to <140\90
¥ Drugs used : CCB(dipins) + Labetolol.
¥ Do not use nitro deugs because they cause increase in intra cranial pressure.
• If Ischemic : Should not lower the BP as it will decrease the blood ßow to brain.
¥ Only decrease BP in case of >220\120mmHg by using CCB/ Labetolol.
¥ Can use thrombolytics with altaplse or reteplase but best time is within 3hrs upto
4.5hrs.
¥ Also use anti clotting,anti platelet drugs-aspirin, Clopidogrel, Enoxaparin,
Abciximab etc..
¥ Also correct lipid proÞle,sugar level,weight loss if obeisity, Diet control.
• C/I of thrombolytics :
- Hemorrhagic shock
- Age <18 yrs
- Any clotting or bleeeing disdorder Recent MI/Surgery in last 14 days.
- HTN >185\110mmHg
- 10% Mannitol used for raised ICP.
 MYASTHENIA GRAVIS

¥ Neuromuscular junction diesase (LMN lesion)

Pathophysiology
¥ Auntoimmune disease type-II HS HLA-DR3,B8.
¥ Auto antibodies against Ach receptors,LRP4 Musk(muscle speciÞc kinase).
- Since less receptors, there is ßaccid paralysis/paresis, increased weakness
on evenings and exertion.
¥ 65% patient show thymus hyperplasia and 10% can show thymoma most
common is anterior mediastenal tumor.
¥ Females>males,young females 20-40years and elderly male 50-70 years.

Clinical features
¥ Bilateral asymmetrical ptosis and diplopia-earliest Þndings
¥ Facial muscle weakness : Snarling face.
¥ CoganÕs lid twitch
¥ Bulbar involvement (dysphagia,dystonia,dysarthria etc)
¥ Limb involvement-difÞculty in standing,walking etc
¥ If respiratory muscle affected-death
¥ Myasthenia crisis : Severe weakness precipitated by infection, stress, pregnancy.
¥ Normal sensury system, Normal IQ, Normal deep tendon reßex, No babinski
sign.

Investigation
¥ Most sensitive is Single Þbre EMG. But most speciÞc is Anti Ach receptor
Antibody detection.
¥ Normal nerve conduction.
¥ On repetitive nerve stimulations : Decremental Response.
 Note : In lambert eaton syndrom,which is similar to myasthenia gravis, Flaccid
paralysis due to Ca2+ channel defect causing decreased Ach release, but incremental
response on RNS and exertion improve strength of contraction due to more Ach
release.

Other Investigations :
1. Icepack test : On applying Icepack on eyelid Low Temperature inhibit
cholinesterase (break Ach) and increased Ach reduce Ptosis.
2. Tensilon /edrophonium test : obsolete now
- Edrophonium inhibit cholinesterase and increase Ach and hence improve the
muscle strength.
- 2mg IV edrophonium : but increased Ach can cause cholinergic crisis.
- Rx : Atropine

Snarling face

Icepack test
Treatment
¥ Cholinesterase inhibitor : Neostigmine, Pyridostigmine (doesnt cross BBB)
¥ Pyridostigmine has longer activity.
¥ DOC of Myasthenia crisis : Steroids, Imuuniglobulins, Plasmapheresis.
• Surgery : Thymectomy.
 GULLIAN BARRE SYNDROME

Pathophysiology
¥ Initially, there is infection, then antobody against gangliocytes(myelin) formed.
This cause demyelinating. polyneuropathies (sensory,motor,autonomic).
¥ Polyneuropathies are usually LMN lesions and cause ßaccid paralysis

Variants of GBS
1. Acute Inßammatory demyelinating polyneuropathies.
2. Acute motor axonal neuropathy(AMAN)
3. Acute motor sensory axonal neuropathy(AMSAN)
4. Acute sensory neuropathy.
Antibodies in GBS
¥ GM1Antibody
¥ GM16. Antibody. : Present in AMAN& AMSAN.
¥ GM1a Antibody
¥ GD1b Antibody : Present in ASN.
¥ Gq16 Antibody

Infections
¥ MC are respiratory infections(70%) than GI infections.
Eg : Campylobacter jejuni
¥ Respiratory virus : EBV, CMV, Zika, Adeno. Rhimo, RSV.
¥ Bacteria : Mycoplasma, H.inßuenzae
¥ Sometimes vaccines cause GBS
Clinical features :
¥ LandryÕs ascending Paralysis.
¥ Bilateral symmetrical ßaccid paralysis starting from lower limb.
¥ Ist to be lost is ankle jerk deep tendon reßex,then knee jerk lost, Patient cant stand
or walk.
¥ Involve trunkal and upper limb muscles even can cause death if respiratory muscle
involved (rarely).
¥ Bulbar involvement : MC affected VII nerve also dysphagia, dysarthria.
¥ Also involve sensory nerves, loss of vibration, proprioception and Parasthesia.
¥ Autonomic loss-nowel/bladder Dysfunction, Impotence.

Investigations
¥ IOC : Nerve conduction velocity For neuropathies.
¥ GBS,Þndings are :
- Decreased Velocity (due to demyelination).
- Increased latency(increasd time).
- Abnormal Muscle reßex.
- Decreased amplitude.
¥ Most SpeciÞc Test : Antibody detection

Treatment
¥ Most patients recover well with few weeks(good prognosis).
¥ Immunoglobulins and plasmapheresis used

Botulinum Toxin

¥ Inhibit Synaptobrevin (Snare protein).

¥ Less Ach release : descending ßaccid muscle paralysis.
¥ Hence botox used for treatment of spasm/spasticity, Achalasia cardia,wrinkle
removal.
 GBS MG

¥ Ground to brain ¥ Mouth to ground

¥ Ascending Pathway ¥ Ptosis, Face.
¥ deep tendon reßex absent ¥ deep tendon reßex present.

SPINAL CORD

Motor Sensory and ANS function.

¥ Motor Contain : Pyramidal tract.
¥ Sensory Contain : Ascending Tract.
¥ ANS Function: - Sympathetic : Thoracolumbar.
- Parasympathetic : Sacral S2 S3 S4.

Ascending sensory tract

¥ Dorsal Column(In posterior cord).

¥ Carry Þne Touch, Pressure, Proprioception.

Subthalamic Tract
¥ Lateral : Pressure & Temperature.
¥ Anterior : Itching & Crude sensation.

• Dorsal column : Remain uncensored in spinal cord and cross to opposite side in
medulla.

¥ DC lesion : In cord cause loss of touch, pressure on Ipsilateral(same side)

¥ Subthalamic Tract : crossed tract, cross to opposite side Itself (2-3segments up).
¥ Sub thalamic tract lesion : cause contra lateral loss of pain and temprature.
 SPINAL CORD SYNDROME

1. Brown Sequard Syndrome(BSS)

¥ Hemisection of spinal cord(R/L).
¥ All sensation autonomic,motor loss on same side but less of pain,temprature
on opposite side.
Ex : Touch, pressure, propriception
- Spastic paralysis (pt lession).
- Autonomic lession

2. Central cord syndrome of syringo myelia

Syrinx formed in central canal mainly cervical region.

#
Cause : B/L sensory moter loss (pt lession) in upper limbs, chest, back area.
¥ Spastic paralysis of U/L limbs.
¥ It affects crossing Þbres of STT-loss of pain and temprature,but Intact touch and
pressure.
¥ Investigation : MRI
¥ Treatment : Syringostomy
Tabes Dorsalis : (Neurosyphilis)

¥ Mainly affect dorsal column

¥ Intact pain and temperature
¥ Loss of touch and proprioception
¥ Cannot feel ground : Sensory Ataxia Stumping gait : (Diabetic and
sensory neuropathies).

SUMMARY

SYNDROME TOUCH PAIN AND

TEMPERATURE

Brown S syndrome. Negative on same side Negative on opposite sides.

Syringomyelin Positive intact Negative B/L, upper body.

Tabes dorsalis Negative lower body Positive intact.

Conus medullaris and cauda equina syndrome

¥ Spinal cord ends at L1 in adults and L3 in children ends in CM (L1) and remain
lumbar and saeral nerves comes out looking like horse tail c/a cauda equira
¥ CM and CE compression : Sensory, Motor and autonomic disturbances.
¥ CM- (L1 , B/L)- Perianal anesthesia, (more ßadder) -CE- (L1, L2, U/L).-More
radicular pain saddle anaesthesia.
5 HEPATOLOGY

• Function : Metabolism
Dual blood supply (1500ml/min).

1. Portal vein
• 1200ml/min.
• Blood from GIT
2. Hepatic artery
• 300ml/min.

Liver : Make (anabolic) :

• Lipids, Lipoproteins, Glycogen, Fats.
• Proteins : Plasma proteins, clotting factors.
• Albumins, alpha beta globulins.
• Also Store VIT-A in Ito cell/Stellate cell.

Breakdown(catabolism) it metabolises the drugs, toxins, alcohol and

make them water soluble so that kidneys can excrete.

NH3 Liver Urea

Protein& Amino acids Urea cycle Excreted in urine by
Metabolism Also GIT kidney.
bacteria

• Liver Disease : Increase NH3.

• Kidney Disease : Increase Urea.
• RBC Breakdown(hemolysis) occur in spleen(littoral cell) and liver(Kuppfer cells).
• Normal RBC lifespan#120days.

RBC breakdown
"
Hemoglobin released

Haem Globin chains

"
Biliverdin(green)
"
Bilirubin(yellow)unconjugated
lipid soluble(cant come in urine)
It travels,bound to plasma bodies.

Liver convert unconjugated bilirubin.

UDP #Glucoronyl transferase

Conjugated bilirubin

• Conjugated bilirubin won’t come in urine as it is secreted into intestine bia bile
duct along with bile salts&acid,which helps in fat digestion & absorption.
• In intestine,bacteria convert conjugated bilirubin to stercobilin,which is lost in
feces&some stercobilin can be absorbed back to liver(enterohepatic circulation)
& excreted in urine as urobilin.
• Increased hemolysis : Increased unconjucated bilirubin.
- Pre-hepatic jaundice.
- Increase bilirubin >2mg%
- Newborn>5mg%.
Bile duct obstruction
• Conjugated bilirubin regurgitate into blood Increased conjugated bilirubin will
come in urine & cause(dark yellow urine)Choluric jaundice. Also known as
Post-hepatic jaundice.

Hepatic jaundice

¥ Inßammation of liver
• Increased unconjugated Bilirubin-liver fail to conjugate Increased
conjugated bilirubin : liver conjugate,but it can’t be secreted due to micro-
obstruction.
 Patient of jaundice
(Yellow sclera)
#
Ask urine colur

Normal Unconjugated Dark yellow Conjugated

bilirubin. bilirubin.
# #
Hb,RBC,splenomegaly Hepatic/post hepatic
#
Pre-hepatic jaundice. ALT/AST. Alk.Phos
# #
Hepatic jaundice USG,ERCP
# #
Fever,abd.pain in right upper Gold st :HIDA
quadrant.
#
Hepatitis

VIRAL HEPATITIS

• Hepatitis A- MCC orofecal route,asymptomatic

• Hepatitis E-orofecal route,fulminant hepatitis in pregnancy.
• Hepatitis B,C,D : blood and sexual route (IV drug user,infected needle same as
HIV AIDS).
Treatment :
Hep.B & HIV : 3 drugs

Tenofovir, Entecavir, Lamivudine

 • Hep.C-causes chronic hepatitis
• Hep.D-co-infection with Hep.B =fulminant hepatitis
• Hep.B- DNA virus.

Serology :

• S antigen(start) -Ist HbsAg-indicate active infection

• E antigen(infectivity)
- Replication&infection started.Also use HBV DNA for checking infection
• C-antibody(immune response)-Anti HbC antibody IgM-acute inßammation
IgG-chronic inßammation
• E-antibidy(infection decreased)
• S -antibidy(revovery test)Anti HbS Ab
- Recovery and immunization & protect from future infection.
• Once Anti HbS Ab come positive,HbSAg negative Immunity could be,
- Vaccine immunity -If IgG Anti HbC negative
- Past infection immunity-if IgGAnti HbC +ve
• Infection : HbsAg +ve
- Acute : IgM,Anti HbC.
- Chronic : IgG,Anti HbC.
 ACUTE LIVER FAILURE

• MCC-toxins
• Other-Hep.B,Hep.E in pregnancy
• If <weeks,known as fulminant liver failure
• MCC -Hep D.Co-infection to HepB
Findings
• High INR>1.5 & Increased PT.
• Due defeciency of clotting factors,increaswd risk of hemorrhages
• Hepatic encephalopathy- increased NH3 as liver fail to convert it to urea
• This crosses BBB and damage neurons
Features Of HE
• Earliest sign : change in personality confusion, ataxia, amnesia, apraxia,
ßapping tremors (asterixis), dysarthria,increased DTR,Positive
• Babinski sign,stupor.
• Coma,Hepatic Coma.
• EEG : Abnormal triphasic waves.

Other features
• Jaundice, ascites, edema, nausea, vomiting, caput medusa.

Investigation
• Increased bilirubin,decreased Albumin,Increased INR,Increased PT,increased
Liver enzymes,Increased alkaline phosphatase.increased ammonia etc.
Treatment.
• L-ornithine,L-arginine (LOLA)
• DOC for Hepatic encephalopathy-NG-lactulose
- Removes GIT bacteria(make ammonia)
• Antibiotics-Rifaxamine,neomycin
¥ Fresh frozen Plasma to correct clotting factor deÞciency 5% dextrose to correct
hypoglycemia
• IV mannitol to reduce cerebral edema.
• Last treatment : liver transplant (MELD Score).
• Model for End Stage Liver Disease

MELD SCORE : 3 Main Parameter

1. Serum Bilirubin.
2. INR.
3. Serum Creatinine.
 CIRRHOSIS

¥ End stage liver disease-Þbrosis amd regenerative nodules.

• Causes : MC :- Alcoholic liver disease.
- Hepatitis B,C.
- Non alcoholic fatty liver disease.
- Non alcoholic steatosis.
- Metabolic disorder=wilson disease
- Hemochromatosis.
- Biliary cirrhosis

Clinical features :

• Jaundice,ascites,palmar erythema.
• Spider angioma(dilated arteries).
• Xanthoma(Fat deposits)
• Clubbing
• Caput medusa(dilated veins around umbilicus).
• Hepatic halitosis-bad mouth smell.
• Bleeding disorder/purpura, Pedaloedema.
• Gynecomastia
• Terry’s nails
• Hepatic encephalopathy.
 Spider angioma

Xanthoma

Child Pugh classiÞcation of Cirrhosis :

• Serum bilirubin increases.
• Serum albumin decreases.
• PT increases.
• Ascites.
• Hepatic encephalopathy.
Treatment :
• Similar to liver failure/hepatic encephalopathy
 PORTAL HYPERTENSION

• MC complication of uncompensated cirrhosis Increased pressure >10mmHg

• It causes development of Porto-systemic collaterals.
¥ IOC : Doppler(for ßow)
- Earliest Þnding : Splenomegaly.
- Most reliable sign : Ascites.
¥ Increased pressure cause increased Þltration of ßuid into peritoneal cavity
known as ascites.

Treatment :

¥ Paracentesis/Tap to remove ßuid

• Check Serum Ascites albumin gradient. If increased SAAG, diagnosis
of Portal Hypertension.

Portosystemic collaterals causes :

• Esophageal varices: bleeding
• Rectal hemorrhoids
• Caput medusa Lumbar & omental veins.
• Bare area of liver

Varices : Hematemesis
• Source of bleed is coronary veins : can cause shock & death.
Treatment :
• DOC-IV octreotide(telipressin)
• TOC : Upper GI endoscopy & banding sclerotherapy.
- Arrange blood,can need massive blood transfusion
If varices :
- bleeding DOC : Octreotide.
- Non-bleeding DOC : Propanalol.
• Sangstaken blackemore tube : for decompression of varices
• If bleeding not controlled- next step Repeat endoscopy
• Surgical intervention-TIPSS shunt.
 INFLAMMATORY BOWEL DISEASE

FINDINGS CROHN DISEASE ULCERATIVE COLITIS

GIT involved Diffuse spare rectal area. Rectum and colon

Lesion Skip lesion continous

Inßammation Transmural(all layers) mucosa/submucosa

Cobble stone Polyps,ulcers,high risk of

Histopathology Creeping fat colon cancer,toxic megacolon,
String sign lead pipe on barium enema.
Fissure/Þstula

Clinical features Crampy abdominal Bloody diarrhea

pain,obstuction Þstula

Treatment Steroid 5ASA-more effective Steroid-5ASA (Aspirin)

(aminosalicylic acid). Colectomy is curative.

Cobblestone appearance String of Kantor sign

Creeping Fat

Lead pipe on Ba enema

Toxic megacolon

CELIAC DISEASE
• Gluten hypersensitivity(Type II)
• HLA DQ2/8 Autoantibodies(TTG,EMA)
¥ Villous atrophy,mucosal imßammation
• Rx-Avoid(BROW) Barely,Rye, Oats, Wheat.
6 HEMATOLOGY

Hemopoesis
• Ist trimester : yolk sac(start at 3 weeks).
• IInd trimester : liver (12th week).
• IIIrd trimester : bone marrow(20th week).
• New born : all marrow.
¥ Adults : long & ßat bones.

Hematopoesis

Lymphoid leukemia : Increased WBC

count >11000/cumm.
1. Acute ALL : MC in children
(increased lymphoblast)
- Size more than RBC.
 2. Chronic CLL : seen in adults
- Increased lymphocytes in peripheral smear.
- Lymphocyte similar to RBC size.

ALL associated with EBV

• Ebstein barr virus

- Burkitt lymphoma.
- Kissing disease
• ALL-t(8,14)chromosome

Starry sky appearance

Diagnosis :
• Flow cytometry
• Bone marrow biopsy
• Histopathological examination
Common Myeloid Precursors

1. Proerythroblast! normoblast! rericulocyte! RBC

2. Megakaryocyte# platelets

3. Myeloblast# all other WBCs (esinophil,basophil, monocyte,neutrophil) Increased

in CML.

Myeloblast : Larger in size.

- Cause Acute Myeloid Leukemia(AML)

Auer Rods & MPL

 FEATURES ALL AML

Myeloperoxidase Absent Present(auer rod).

Sudan black Negative Positive.

Non-speciÞc esterase may be absent or Present

present.
Periodic acid Schiff Maybe positive or
(PAS) Positive. negative.

• In acute : More cytopenia,very low RBC & platelets, increased WBC,

Increased Blast cells Younger patients.
• In chronic : elderly-Hb,RBC low.

Treatment :

• CLL : Rituximab,ßudarbine
• CML : Imatinib
• ALL : Vincristine, Dexamethasone, Anthracyclines
• AML : Cytarabine+ Anthracyclines, Doxorubicin.
 ANEMIA
ClassiÞcation based on mechanism :

1. Blood loss
• Acute : Trauma.
• Chronic : GI lesions.

2. RBC Destruction
• Membrane defect : Hereditary spherocytosis, PAN.
• Enzyme defect : G6PD.
• Immune mediated : Autoimmune hemolytic anemia.
• Hb defect : Sickle cell anemia, Thalassemia.

3. RBC Production
• Nutritional anemia
¥ Iron deÞciency anemia,megaloblastic,sideroblastic

ClassiÞcation based on MCV

1. Macrocytic (MCV >100ß)

• Megaloblastic anemia
• Hypothyroidism
• Alcoholism

2. Microcytic (<80fL)
¥ Iron deÞciency anemia
• Soderoblastic
• ACD
• Thalassemia

3. Normocytic
• Aplastic anemia
• ACD
MCH : Mean Cell Hemoglobin ;normal=27-33
MCV : Mean Cell Volume;normal=80-100ß
MCMC : MCH/MCV=33-37g/dl
• Low MCMC in : Iron deÞciency Anemia.
• High MCMC in : Hereditary Spherocytosis.
• Normal MCMC in : Megaloblastic Anemia.

Poikilocytosis : variation in shape of RBC

Anisocytosis : variation in size of RBC.
RDW(Red cell Distribution Width) : 11.5-14.5 (average of size variation).
7 RHEUMATOLOGY

SYSTEMIC LUPUS ERYTHEMATOSUS

Female >male
Autoimmune disease
Auto antibodies :
¥ Antinuclear Ab(ANA)High sensitivity but poor speciÞcity.
• SM antigen
• Anti smith Ab
• Anti dsDNA Ab
• Anti phospholipid Ab(anti cardiolipin Ab) also seen in syphilis
High correlation to sun exposure.

Cardinal manifestations

1. RASH
• Malar Rash : Butterßy Rash.
• Discoid Rash : Seen in Arm, Leg, Scalp after Sun Exposure.

Malar Rash Discoid Rash

2. Serositis
• Pericarditis, Peritonitis, Pleuritis, Libmann sac endocarditis.

Libmann sac endocarditis.

3. Blood
• Everything low(pancytopenia) : Anemia, Thrombocytopenia, Leucopenia.

4. Mucosal ulcers

5. Neurological manifestations
• headache,seizures, psychosis,mood disorders.

6. Joints
• Non-erosive arthritis/joints involved similar to rheumatoid
arthritis,MCP,rheumatoid factor positive Function is preserved
• Swan neck deformity.
7. Nephritis
• Diffuse proliferative GN (immune complex deposition type III HS.
Diagnosis : 4 positive out of 11 criteria

Treatment :

• Avoid sun exposure

• If mild : NSAIDs
• If moderate : Steroids(prednisolone/hydrocortisone).