One of my fav it may look little big ( bcz of font size and

space)but
I can’t ignore fact they ask any question from medicine nd I
tried to give my concept for this legendary subject .

And as I have to cover all 3 exams neet,INICET,upsc cms , ppl

who want to appear for university exam keeping in mind made
this.

I’m allowing download option in this u can highlight yourself

but concepts are fully retained…. Also stroke topic and other
neuro related topics covered in physio.

I’m Waiting to hear your feedback.

DEFINITIONS
Pneumonia

Syndrome of an acute infection of one or both the lungs caused by bacteria, virus, or fungi
and usually characterized by clinical or radiological signs of consolidation.

Causes of Pneumonia

Infective Causes Non-infective Causes

1. Bacterial (Most common) 1. Chemical injuries

2. Viral 2. Radiation

3. Fungal 3. Physical damage due to neighboring structures

Pneumonia vs Pneumonitis

• Pneumonia: Infection of alveoli (Viral/Bacterial).

• Pneumonitis: Inflammation of alveoli due to Chemical, Radiation, or Immune-

mediated causes.

Key Points

• The infection is at the level of Alveoli of the Lungs.

• It can be a chronic infection as well, but it is rarely seen.

• It is an Inflammatory condition of the Lung/Lungs or a part of lung/lungs (lobes).

Mechanisms of Lung Defense
• Mucous entrapment

• Ciliary clearance

• Immune surveillance (usually by IgA)

• Intact epithelium

• Secretions from mucosa (IgA or surfactant proteins)

• Defensins
Disrupting or overwhelming these defense mechanisms can allow microbes to colonize the
lungs, resulting in pneumonia.

Flowchart: Smoking affecting the Defence Mechanisms of Lungs and eventually

causing Pneumonia

| Epithelial barrier affected → Reduced Ciliary clearance → Reduced Mucous production →

IgA performance reduced → Pneumonia |

Smoking is the most common risk factor causing pneumonia.

Factors favouring colonisation:

Risk Factors for Community-Acquired Pneumonia

1. Cigarette Smoking
2. Age

◦ Extremes of Age (>65 years)

3. Chronic URTI

◦ Sinusitis

◦ Post-nasal drip

◦ Chronic granulopharyngitis

4. Alcohol

◦ Inebriation can cause aspiration

5. Immunodeficiencies

◦ Congenital: Factor deficiencies, Ig deficiencies, T-cell deficiencies

◦ Acquired: HIV, Diabetes, Steroids, Immunosuppressive drugs

6. Splenectomy

◦ Reduced Opsonization resulting in lowered Immunity

7. Chronic Respiratory Diseases

◦ Bronchial Asthma

◦ COPD

◦ Cystic Fibrosis

◦ Bronchiectasis

8. Airway Obstruction
 ◦ COPD

◦ Tumour/Malignancy

9. Air Pollution
TYPES BASED ON EFFECTS & PATTERNS OF MICROBIAL
COLONIZATION IN PNEUMONIA

1. Alveolar

• Increase in Purulent exudate which fills the alveoli

• Presence of Neutrophils & Erythrocytes in alveoli

2. Lobar

• Consolidation observed in Entire Lobe

• Common causative agent: S. pneumoniae, H. influenzae

3. Bronchopneumonia

• Bilateral Patchy distribution

• Most commonly occurring secondary to a Viral infection

• Other causative agents: Staphylococcus, Pseudomonas

4. Interstitial

• Predominantly involves the wall with Fibrinous exudate

• Mononuclear WBCs observed

5. Atypical

• Diffuse interstitial pattern ± perihilar concentration

• Causative agents: Mycoplasma, Chlamydophila, Legionella

• Can also be secondary to Influenza

Aetiology of Pneumonia

Pneumonia Causative Agents

Bacterial Pneumonia Non-bacterial Pneumonia

1. Streptococcus pneumoniae (Most common)

1. Viral:
2. Hemophilus influenzae (2nd Most - H. influenzae (Most Common)
Common) - H1N1, H5N1, SARS-COVID (2nd
Most Common)
- MERS virus, Respiratory syncytial
virus, HIV, CMV & EBV

3. Moraxella catarrhalis (3rd Most common)

4. Staphylococcus aureus 2. Fungal:

5. Bacteria causing Atypical Pneumonia: - Pneumocystis jirovecii, Histoplasma,
- Legionella pneumophila Blastomyces, Coccidioidomycosis,
- Mycoplasma pneumoniae Para-coccidioidomycosis
3. Parasitic
6. Bacteria causing Hospital Acquired 4. Non-Infective:
Pneumonia: - Radiation, Chemical, Drug reactions,
- Klebsiella, Pseudomonas Lipid/Lipoid
7. Other Bacteria:
- Streptococcus pyogenes, Chlamydia
pneumoniae, C. psittaci, C. trachomatis,
Coxiella burnetii
Morbid's Anatomist's Classification of Pneumonia

Classification Most Common Causative Agents

Lobar Pneumonia Streptococcus, H. influenzae, Klebsiella
TB, Atypical organism, Staphylococcal
Segmental Pneumonia
infection
Sub-Segmental Pneumonia Virus, TB
Bronchopneumonia (Lobular
Atypical organism, Virus
Pneumonia)

Microbiologist's Classification

1. Infectious

• Bacterial

• Viral

• Fungal

• Others

2. Non-Infectious

Source Classification

• Community Acquired

• Hospital Acquired

• Immuno-deficient

• Post-op/transplant

• Nosocomial Pneumonia

Comparison of Lobar vs. Lobular Pneumonia

Lobular Pneumonia
Feature Lobar Pneumonia
(Bronchopneumonia)
Oedema fluid Large amount Small amount
Underlying Diseased (bronchiectasis, chronic
Normal
Lung bronchitis)
Most common Staphylococcus, Viral, G -ve
Streptococcus & Klebsiella
organisms bacteria
Homogenous opacity with positive Air Patchy multifocal with negative air
CXR
bronchogram sign bronchogram sign

Community Acquired Pneumonia

• Exposure to the organism occurs in the Community

• Types:

◦ A. Classical/Typical Community Acquired Pneumonia

◦ B. Atypical Community Acquired Pneumonia

Features

Features Classical/Typical Atypical

Onset Severe acute form Subacute

Anatomical type Lobar Diffuse, Interstitial

Causative organism Streptococcus, H. influenza Virus, Atypical bacteria

Clinical Presentation

• Fever

• Pleuritic chest pain

• Dyspnoea

• Cough with productive sputum:

◦ Rusty sputum – Pneumococcal

◦ Red currant jelly – Klebsiella

◦ Greenish sputum – Anaerobic or Pseudomonas

◦ Blackish sputum – Aspergillus

Signs of Consolidation

Clinical Signs Radiological Signs

Increase Tubular Bronchial Breath Sounds

Crepitations
Homogenous opacities
Increased Vocal Resonance
Air bronchograms
Increased Vocal Fremitus
Egophony

Classical Feature: Tubular bronchial breathing with crepitations & egophony

Stages of Pneumonia
Stage of Congestion

• Crepitations, Increased Vocal resonance & Vocal fremitus

Stage of Hepatization/Consolidation

• Crepitations, Increased Vocal resonance & Vocal fremitus

• Tubular Bronchial Breathing (only observed in consolidation stage)

Stage of Resolution

• Crepitations, Increased Vocal resonance & Vocal fremitus

X- ray Findings: Homogenous opacity with multiple air bronchograms

Pneumococcal Pneumonia
• Organism: Streptococcus pneumoniae

• Consists 90% of Community-based pneumonia

• Predisposing factors: Smoking, underlying lung disease, mild immunodeficiency

• Treatment:

1. Penicillin

2. Ceftriaxone
Atypical Pneumonia
Patchy opacities observed in Atypical Pneumonia
Extrapulmonary Symptoms

Symptoms Infectious Agent

Legionella and
Myalgia, arthralgia, and malaise
Mycoplasma
Myocarditis and pericarditis Mycoplasma pneumoniae
Headache, abdominal pain, diarrhea, vomiting Legionella pneumoniae
Labial herpes simplex reactivation Pneumococcal pneumonia
Skin rashes: Erythema multiforme, erythema
Mycoplasma pneumoniae
nodosum

Walking Pneumonia

• Less symptomatic

• Patients with Atypical pneumonia may be mobile but on X-ray, opacities are observed.

• Classically seen with Mycoplasma

Type of Pneumonia: Bronchopneumonia or Interstitial pneumonia

Diagnosis

• PCR & Serology

• CXR - Interstitial pattern

Treatment

• Macrolides

• Quinolones
Radiological Findings

Types | Features | X-ray Findings

Types Features X-ray Findings

- Lobar consolidations ![Fig. Lobar
1. Alveolar (Airspace) - Air Bronchograms Consolidations]
Pneumonia - M/c organism: S. pneumoniae & K. ![Fig. Air
pneumoniae Bronchograms]
- Multifocal patches
2. Bronchopneumonia (Lobular - U/L or B/L ![Fig. Multifocal
pattern) - Causative agents: Staphylococcus, Patches]
Pseudomonas

Types Features X-ray Findings

- B/L shadows
3. Interstitial - Present in all lung zones
Diffused pattern B/L lungs
Pneumonia - M/c with Viruses, Mycoplasma, P.
carinii
- Characteristic sign in Klebsiella
4. Bulging Fissure pneumonia
Bulging Fissure Sign]
Signs - Present due to interlobar effusion
or excess exudate
- Perihilar shadows
5. Pneumocystis Perihilar shadows & cystic
- Multiple cystic shadows
pneumonia (PCP) shadows in PCP
- Organism: Pneumocystis jirovecii
- Observed in middle lobe
6. Silhouette Shadow/
consolidation Silhouette Shadow
Sign
- Homogenous opacity

Assessment of Severity in Pneumonia

CURB 65 Criteria

• C - Confusion

• U - Urea level >19

• R - Respiratory rate >30

• B - Blood Pressure (Systolic <90, Diastolic <60)

• 65 – Age
Presence of any 2 criteria is an indication of hospital admission.
TREATMENT OF PNEUMONIA
Antimicrobial Therapy (ATS)

Anti-Microbial Therapy based on Patient Stratification

Group 1 Group 2 Group 3 Group 4

- C/P Disease and/or Modifiers

with Risk factors are admitted in
- No C/P Disease,
Inpatient department.
No comorbidities
Intravenous intervention - ICU admitted patients
- Advanced
- Presence of C/P required. A. No risk for P.
Generation
disease or a. Intravenous β lactam + i.v. or aeruginosa - i.v. β lactam
Macrolides: a.
Modifiers. per oral Macrolide/ Doxycycline + i.v. Macrolide/ - i.v.
Azithromycin b.
a. β lactam + - Ceftriaxone - Amoxicillin + Fluoroquinolone
Clarithromycin c.
Macrolide or Clavulanic acid - Cefoperazone B. Risks for P. aeruginosa
Doxycycline
Doxycycline - + Clavulanic acid - Macrolides - Selected i.v.
- Doxycycline in
Cefotaxime - like azithromycin or antipseudomonal β lactam
cases of
Cefuroxime - clarithromycin are added + i.v. Anti-pneumococcal
suspected
Amoxicillin + a. Intravenous Anti- fluoroquinolones-
Atypical infection
Clavulanic acid pneumococcal fluoroquinolones Ciprofloxacin
or in case of
high dose b. If suspicion of Staphylococcal Anti-pseudomonal
allergy towards
b. Anti- infection, then Intravenous antibiotics:1. Piperacillin
azithromycin &
pneumococcal Vancomycin + Tazobactam 2. Cefepime
clarithromycin
fluoroquinolones - Patient without C/P disease or 3. Imipenem/ Meropenem
- <1.5 %
(alone) - modifiers presenting with other 4. Colistin 5. Ceftazidime
mortality rate,
Levofloxacin complication: a. i.v. (if patient has no Renal
hence managed as
Azithromycin alone or β lactam failure) 6. Amikacin
Outpatient
+ Doxycycline b. Anti-
treatment.
pneumococcal fluoroquinolones
(alone) - Levofloxacin

Anti-pneumococcal fluoroquinolones: Moxifloxacin, Gatifloxacin, Sparfloxacin,

Levofloxacin
Duration of therapy: Outpatient- 7 to 10 days & Inpatient - 10 to 14 days

When to shift patient from Intravenous therapy to Oral therapy?

• Patient should be symptomatically better (reduction in cough, dyspnoea)

• Afebrile (twice 8 hours apart)

• WBC shows decreasing trend

• Patient should tolerate oral dosage

 COPD
Global Initiative for Chronic Obstructive Lung Disease (Gold Guideline)

DEFINITION
COPD is a preventable and treatable pulmonary disease associated with some significant
extrapulmonary effects that may contribute to the severity in individual patients.

• Pulmonary component is characterized by persistent respiratory symptoms and airflow

limitation that is due to airway or alveolar abnormalities usually caused by significant
exposure to noxious particles or gases

• Airflow limitation, Not Fully Reversible, usually Progressive.

• 4th leading cause of death

• Burden projected to increase due to increasing risk factors and aging population

TYPES OF COPD

Emphysema

• Abnormal and permanent enlargement of the airspaces distal to the terminal

bronchioles accompanied by destruction of the airspace walls without obvious fibrosis
(i.e. there is no fibrosis visible to the naked eye).

Chronic Bronchitis

• Chronic productive cough for three months in each of two successive years in a patient
in whom other causes of chronic cough (e.g. bronchiectasis) have been excluded.

Small Airway Disease

• A condition in which small bronchioles are narrowed.

PATHOGENESIS

• Airflow limitation - small airway obstruction and emphysema.

• Small airways narrow due to hyperplasia and accumulation of cells, mucus, and
fibrosis.

• Chronic inflammation which triggers the activation of transforming growth factor-β

(TGF-β) contributes to airway fibrosis, whereas absence of TGF-β may produce
parenchymal inflammation and emphysema.
Types of CB

• Simple Chronic Bronchitis

• Chronic Mucopurulent Bronchitis

• Chronic Asthmatic Bronchitis

• Chronic Obstructive Bronchitis

Pathology Pathogenesis Pathophysiology

Chronic Airflow limitation and gas
Oxidative stress
inflammation trapping
Structural changes Protease-antiprotease imbalance Gas exchange abnormalities
Inflammatory cells Mucus hypersecretion
Inflammatory mediators Pulmonary hypertension
Peribronchiolar and interstitial fibrosis

Pathogenesis

• Irritants cause inflammation with infiltration by CD8+ T-lymphocytes, macrophages,

and neutrophils.

• Hypersecretion of mucus

• Hyperplasia/hypertrophy of submucosal glands in large airways (trachea and

bronchi). Develops as response to inhaled environmental irritants and proteases
released from neutrophils (e.g., elastase and cathepsins). This leads to hypersecretion
of mucus.

• Marked increase of goblet cells in small airways (small bronchi and bronchioles):
They produce excessive mucus.

• Mucus plugging of bronchial lumen.

• Inflammation and fibrosis of bronchial wall.

BODE INDEX

• A multidimensional prognostic index.

• Considers several indicators of COPD prognosis

◦ Body mass index [BMI]

◦ Obstructive ventilatory defect severity

◦ Dyspnea severity

◦ Exercise capacity

• A BODE score greater than 7 is associated with a 30% 2-year mortality.

• A score of 5 to 6 is associated with 15% 2-year mortality.

• If score is less than 5, the 2-year mortality is less than 10%.

MANAGEMENT (MCQ)

General Measures

• Regular exercises and management of nutritional status.

• Weight loss, if the patient is obese.

Reducing exposure to noxious particles and gases that cause bronchial irritation

• Smoking cessation

• Reduce smoke: Reducing the risk from indoor and outdoor air pollution. Reduce
exposure to smoke from biomass fuel, particularly among women and children.

• Avoid: Dusty and smoke-laden atmospheres.

DRUG THERAPY
Used both for the short-term management of exacerbations and for the long-term relief of
symptoms.

• Bronchodilators: They are central to the management of breathlessness.

• Beta 2-Adrenergic agonists: The inhaled route is preferred.

◦ Mild disease: Short-acting agents, salbutamol or terbutaline.

◦ Moderate-to-severe disease: Long-acting agents, salmeterol or formoterol or

indacaterol, SABA (Short-acting beta-agonists) and LABA (Long-acting beta-
agonists).

• Antimuscarinic (anticholinergic) drugs: More prolonged and greater bronchodilation

is achieved by adding ipratropium bromide or tiotropium bromide or oxitropium in
severe disease.

• Phosphodiesterase type 4 inhibitors: Roflumilast.

• Corticosteroids

• Inhaled Corticosteroids (ICS)- Reduce frequency and severity of exacerbations and

are used in moderately severe COPD.

• Examples: Beclomethasone, budesonide, fluticasone, ciclesonide, flunisolide.

• Oral corticosteroids: Used during exacerbations but avoided as maintenance

therapy due to risk of osteoporosis and impaired skeletal muscle function.
Respiratory Infections

• Bacterial infection precipitates exacerbations.

• Antibiotics: Azithromycin, Tetracycline, Ampicillin, Cotrimoxazole.

• Prevention of infection: Polyvalent pneumococcal and influenza vaccines.

Symptomatic Measures

Anti-Mucolytic Agents:

• Reduce viscosity of sputum and can reduce the number of acute exacerbations and
total number of days of disability.

• Examples: Bromhexine, N-acetylcysteine, carbocysteine, ambroxol, erdosteine.

Antitussives:

• Regular use of antitussives to control cough in stable COPD is not recommended.

Other Measures:

• Chest physiotherapy

• Pulmonary rehabilitation
Emphysema
• Chronic lung disease characterized by abnormal irreversible (permanent) dilatation
of the airspaces distal to the terminal bronchiole.

Types of Emphysema

Centriacinar Panacinar Irregular (Scar or

Distal Acinar (Paraseptal)
(Centrilobular) (Panlobular) Cicatricial)

All airspaces
Affects central/proximal Acinus is irregularly
beyond the terminal Affects distal airspace near
parts of the acini; distal involved and may be
bronchiole are the pleura.
alveoli spared. asymptomatic.
uniformly dilated.

Dilated spaces >1 cm form

Common and severe in More common in
bullae, which may rupture, Most common form
upper lobes, apical lower lobes, most
causing spontaneous of emphysema.
segments. severe at the bases.
pneumothorax.

Associated with heavy Occurs near healed

Associated with α1- Occurs near areas of
smokers, chronic inflammatory
antitrypsin fibrosis, scarring, or
bronchitis, coal worker’s processes (e.g.,
deficiency. atelectasis.
pneumoconiosis. tuberculous scars).

Pathogenesis
• Destruction of alveolar wall, secondary to toxins.

• Mechanism that checks the destruction of alveolar wall:

◦ These include: (1) Anti-elastases (e.g., α1-antitrypsin) and (2) antioxidants. If

these two mechanisms are defective → results in:

▪ Protease-antiprotease imbalance (e.g., α1-antitrypsin deficiency).

▪ Imbalance between oxidants and antioxidants.

• Unchecked inflammation and proteolysis: Develops due to deficiency of the above

protective mechanism.
Genetic Factors - Deficiency of α1-Antitrypsin

• Autosomal recessive.

• α1-antitrypsin is a major inhibitor of proteases (particularly elastase).

• During inflammation, protease (proteolytic enzyme) is secreted by neutrophils and

digests the connective tissue of the lung.

• α1-antitrypsin is a protease inhibitor (antiprotease), preventing this proteolytic

digestion.

• Hence, a deficiency or absence of α1-antitrypsin results in the proteolytic destruction

of the lung. These patients develop severe panacinar emphysema.

Clinical Features

• Appear late, at least one-third of the functioning pulmonary parenchyma is damaged.

• Dyspnea: insidious onset and steadily progresses to breathlessness on trivial exertion

and rest.

• Cough and expectoration of scanty mucoid sputum.

• Weight loss, weakness, anorexia, lethargy.

Dahl’s Sign

• Above knee, patches of hyperpigmentation or bruising caused by constant ‘tenting’

position of hands or elbows.

Hoover’s Sign

• Briefly, during inspiration a paradoxical medial movement of the chest. Normally,

during inhalation, the chest expands laterally, increasing subcostal angle. When
diaphragms are flattened (as in COPD), inhalation paradoxically causes the angle to
decrease.

Harrison’s Sulcus

• A horizontal groove where the diaphragm attaches to the ribs; associated with chronic
asthma, COPD, and rickets.
Percussion

• Hallmark of COPD: Hyper-resonant percussion notes over the lungs.

• Reduced cardiac dullness.

• Liver dullness is pushed down or absent.

• Tidal percussion is negative.

Auscultation

• Diminished intensity of breath sounds.

• Breath sounds are vesicular with prolonged expiration.

• Scattered, faint, high-pitched, end-expiratory rhonchi may be audible.

Clinical Features

Feature Emphysema Chronic Bronchitis

Dyspnea Severe Mild to moderate
Develops after dyspnea
Cough Frequent, develops before dyspnea starts
starts
Sputum Scanty, mucoid Copious, purulent
Mucopurulent relapses Less More
Cyanosis Absent Present
Pulmonary
Late and mild Early and severe
hypertension
RVF, Respiratory
Late and often terminal Repeated episodes
failure
Decreased lumen due to mucus and
Airway obstruction Loss of elastic recoil
inflammation

Investigations
Investigation Emphysema Chronic Bronchitis
Hematocrit
Normal Increased
(PCV)
PaO₂ Normal to low pink puffer Low blue bloater
PaCO₂ Normal, mildly increased High (>40)
FEV₁ Decreased Decreased
Diffusing
Reduced Normal
capacity
Features of hyperinflation, bullae, and Increased broncho vascular markings and
Chest X-ray
tubular heart cardiomegaly
Elastic recoil Decreased Normal
Airway Normal to slightly increased Increased
Cor Late, mild Early, marked
Prognosis Good Poor

Characteristics: Bronchial Asthma vs. COPD

Characteristics Bronchial Asthma COPD

Usually, children and
Age of onset Usually, older individuals
young adults

Family history of allergy,

Smoking, atmospheric pollution, occupational
Risk factors exposure to allergens,
exposure, α1-antitrypsin deficiency
occupational sensitizers

Respiratory Wheezing, cough,

Chronic dyspnea, productive cough
symptoms dyspnea

Vary from time to time

Nature of
and even over hours and Usually, continuous symptoms
symptoms
days

Exercise, dust, or
Triggers Unrelated to triggers
exposure to allergens

Symptoms improve
Recovery of
spontaneously or with Slowly progressive despite therapy
symptoms
treatment

Often present (cardiovascular diseases,

Comorbidities Generally absent metabolic syndrome, depression, osteoporosis,
muscle wasting)

Chest X-ray Normal Hyperinflation

Reversibility of airway
Spirometry obstruction and normal FEV₁/FVC<0.7 and persistent airflow limitation
between symptoms
Treatment - Emphysema

• Bronchodilators and steroids may be helpful.

• Prevention of progression: Cessation of smoking, avoidance of occupational exposure.

• Treatment of infections, respiratory failure, and right heart failure.

• Physiotherapy.

Management

GOLD Stage I. Mild II. Moderate III. Severe IV. Very Severe

FEV₁/FVC FEV₁/FVC FEV₁/FVC

FEV₁/FVC <0.70, FEV₁ 30%
Spirometry <0.70, FEV₁ <0.70, FEV₁ <0.70, FEV₁
of predicted or <50% if
>80% of 50-79% of 30-49% of
respiratory failure present
predicted predicted predicted

Add oxygen therapy, ventilator

Short-acting β₂- Long-acting β₂- Add inhaled assistance, management of
Management agonists as agonists ± glucocorticoids ±
right-sided heart failure,
needed anticholinergics methylxanthines
surgical options

• Avoid risk factors, influenza vaccination, and use short-acting β₂-agonists at all stages.

Exacerbations in the prior year

Symptoms Fewer More*

Fewer <2 Group A
Group B
outpatient Bronchodilator [usually a short-
Bronchodilator [usually a short-acting
acting beta agonist (SABA) or
beta agonist (SABA) or short-acting
short-acting antimuscarinic
antimuscarinic antagonist (SAMA)]
antagonist (SAMA)]

More ≥2
outpatient or ≤ Group D
hospitalization Group C LABA+LAMA →
LAMA → LAMA+LABA LAMA+LABA+inhaled corticosteroid
(ICS)
mMRC 0-1, CAT < 10 mMRC ≥ 2, CAT ≥ 10

taken from original gold guidlines

 Malabsorption Syndrome
• Impaired absorption of one or more dietary nutrients

◦ A pathophysiologic state with multiple etiologies/varied clinical manifestations.

• Dietary Nutrient Absorption-in Small Intestine

◦ Calcium, iron, folic acid - absorbed in proximal small intestine (Duodenum).

◦ Vitamin B12, bile acid - in the ileum.

◦ Glucose, amino acids, lipids - throughout the small intestine (Jejunum).

Three Steps are Required for Normal Nutrient Absorption
• Luminal brush border process.

• Absorption into the intestinal mucosa

• Transport mucosa into circulation.

Malabsorption Disorder Could be

• Primary Malabsorption usually congenital defect

• Secondary Malabsorption usually acquired defect.

MECHANISMS

Luminal Phase (Processing Defect)

• Digestive enzyme deficiency/inactivation.

• ↓Bile salt synthesis; ↓Excretion; ↓bile salt conjugation.

• ↓Gastric acid; ↓intrinsic factor (Pernicious anemia).

• Bacterial consumption of nutrients.

Mucosal Phase

• Epithelial transport defect- Inflammations infections.

• Brush border hydrolysis defect.

• Congenital/acquired disaccharidase deficiency.

Post-absorptive Phase

• Lymphocytic obstruction - Intestinal lymphangiectasia

• Enterocyte processing - Abetalipoproteinemia.

CAUSES

Exocrine Pancreatic Insufficiency

• Ch. Pancreatitis

• Pancreatic CA

• Cystic fibrosis

Inactivation of Pancreatic Lipase

 • Gastrinoma (ZES)

• Drugs (orlistat)

↓Bile Acid (Impaired Micelle Formation)

• Parenchymal liver disease

• Cholestatic liver disease

Bacterial Overgrowth

• Anatomic stasis (Blind loop, Stricture, Fistula)

• Functional stasis (DM, scleroderma)

Interrupted Enterohepatic Circulation of Bile Acid

• Ileal resection (Crohn’s disease)

Drugs (Bind or Precipitate Bile Salt)

• Neomycin

• Cholestyramine

Impaired Mucosal Absorption

• Intestinal resection or bypass

• Inflammation (Celiac sprue, Tropical sprue, Whipple’s disease)

• Classic manifestation- Diarrhea (steatorrhea) weight loss

• Majority - subclinical

• E.g. Celiac disease

Partial (isolated)

• Secondary to diseases that interfere with absorption of specific nutrients.

◦ Pernicious anemia resulting in Vitamin B12

◦ Lactase deficiency cause Lactose intolerance

SIGNS & SYMPTOMS

Nutrient Deficiency Symptoms

Calorie Weight loss with normal appetite
Fat Steatorrhea, Pale, voluminous, greasy offensive diarrhea
Protein Edema, muscle atrophy, amenorrhea
Carbohydrate Abdominal bloating, flatus, watery diarrhea
Macrocytic anemia, Subacute combined degeneration of spinal
B12
cord
Folic acid Macrocytic anemia
Vitamin B
Cheilosis, Glossitis, Angular stomatitis, Acrodermatitis
(general)
Iron Microcytic anemia
Ca & Vit D Osteomalacia (bone pain, pathologic fracture), Tetany
Vitamin A Follicular hyperkeratosis, Night blindness
Vitamin K Bleeding diathesis, Hematoma

TESTS FOR STEATORRHEA

Quantitative Test

• 72hr stool fat collection - gold standard

◦ 6gm/day - pathologic

◦ 20gm/day - Patients with steatorrhea

• Modest elevation in diarrheal disease (May not necessarily indicate Malabsorption)

Qualitative Tests

• Sudan III stain

◦ Detect clinically significant steatorrhea in >90% of cases

• Acid steatocrit - A gravimetric assay

◦ Sensitivity - 100%, specificity - 95%, PPV-90%

• NIRA (Near infra reflectance analysis)

◦ Equally accurate with 72hr stool fat test

◦ Allows simultaneous measurement of fecal fat, nitrogen, CHO

SCHILLING TEST

To determine the cause of cobalamin (B12) malabsorption

• Helps to assess the integrity of gastric, pancreatic and ileal functions.

◦ Abnormal cobalamin absorption in: Pernicious anemia, Chronic Pancreatitis,

Achlorhydria, Bacterial overgrowth, Ileal dysfunction

• Administering 58Co-labeled cobalamin Per Oral (P.O).

◦ Cobalamin 1mg IM 1hr after ingestion to saturate hepatic binding sites

◦ Collecting urine for 24 hr (Dependant on normal renal & bladder function)

• Abnormal- <10% excretion in 24 hrs.

Interpretation of Schilling Test

With With
58Co- 5 Days of
Intrinsic pancreatic
Cbl Antibiotics
factor enzyme
Pernicious Anemia ↓ Normal - -

Chronic Pancreatitis ↓ ↓ Normal -

Bacterial overgrowth ↓ ↓ ↓ Normal

Ileal disease ↓ ↓ ↓ ↓

D-XYLOSE TEST
A Pentose monosaccharide absorbed exclusively at the proximal small intestine.

• Used to assess proximal small intestine mucosal function.

• The test

◦ After overnight fast, 25gm D-xylose P.O.

◦ Urine collected for next 5 hrs.

◦ Abnormal test: <4.5 gm excretion shows duodenal/jejunal mucosal Defect.

• False +ve results:

◦ Renal dysfunction

◦ Inadequate urine sample

 ◦ Impaired gastric emptying, ascites

◦ Drugs (ASA, Indomethacin, Neomycin)

Other tests for carbohydrate malabsorption

• Lactose tolerance test

◦ 50gm of lactose P.O.

◦ Blood glucose at 0, 60, 120 min.

◦ BG <20mg/dl + development of Symptoms – diagnostic

• Breath tests (Hydrogen, 4CO2, 13CO2)

Test for bacterial overgrowth

• Quantitative bacterial count from aspirated small bowel. Normal count: < 100/ml
(Jejunum) >100/ml (Ileum).

Tests for Pancreatic Insufficiency

• Stimulation of pancreas through administration of a meal or hormonal secretagogues.

• Indirect tests-schilling test

Tests for Protein Malabsorption

• Enteral protein loss (Measuring alpha-1 antitrypsin clearance)

Test for Bile Acid Malabsorption

• Selenium-homocholic acid taurine (SeHCAT) test: In this test, Se-labeled bile acid is
given orally.

• After 7 days, total body retention is measured with a gamma camera.

• Retention value of <10% is abnormal.

Acute Coronary Syndrome

• Refers to a spectrum of clinical representations including:

◦ Myocardial infarction:

▪ ST-elevation myocardial infarction

▪ Non-ST-elevation myocardial infarction

◦ Unstable angina

• Acute coronary syndrome (ACS) is almost always associated with rupture of an

atherosclerotic plaque and partial or complete thrombosis of the coronary artery.

• Plaque rupture can occur due to:

◦ Trauma

◦ Stress-related

◦ Arrhythmia

S-T SEGMENT ELEVATED MYOCARDIAL INFARCTION (STEMI)

• STEMI is due to the formation of an occlusive thrombus at the site of rupture of an

atheromatous plaque in a coronary artery.

• S-T segment elevated on ECG

• Can lead to left ventricular failure

To diagnose:

• ≥ 2 mm of ST segment elevation in 2 contiguous precordial leads in men (1.5 mm

for women)

• An initial Q wave develops over a period of several hours to days.

• In addition to patients with ST elevation on the ECG, two other groups of patients
with an acute coronary syndrome are considered to have a STEMI:

◦ Those with new or presumably new left bundle branch block

◦ Those with a true posterior MI (S-T depression can also occur)

• An elevation in the concentration of troponin or CK-MB is required for the diagnosis

of acute MI.

Based on the region involved, STEMI is classified into:

 • Anterior wall STEMI: ST elevation in the precordial leads (V3-V5) (Left anterior
descending artery is involved)

• Lateral wall STEMI: ST elevation in I, aVL, V5-V6 (Left anterior descending

artery is involved)

• Posterior wall STEMI: Reciprocal ST depressions in V1-V3 (ST elevation in

posterior leads) (Right coronary artery or left circumflex artery is involved)

• Inferior wall STEMI (Most common): ST elevation in II, III, and aVF (Right
coronary artery or left circumflex artery is involved)

Other causes of S-T segment elevation:

• Pericarditis

• Benign Early Repolarization

• Brugada Syndrome

• Prinzmetal angina

• Electrolyte disturbances

NON-ST SEGMENT ELEVATED MYOCARDIAL INFARCTION (NSTEMI)

• It is most commonly caused by an imbalance between oxygen supply and oxygen
demand. This imbalance results from a partially occluding thrombus forming on a
disrupted atherothrombotic coronary plaque or on eroded coronary artery
endothelium.

• ST segment elevation is not seen in such cases.

ECG changes seen can be:

• Pathological Q wave - Q-wave ≥ 0.03 s and > 0.1 mV deep

• T wave inversion - In MI, T wave inversion is symmetric - Arrowhead T wave

inversion

Comparison of Unstable Angina, NSTEMI, and STEMI

Unstable
NSTEMI STEMI
Angina

Troponin Normal Raised Raised

 ST elevation Hyperacute T
Normal ECG ST depression Can be
ECG waves New LBBB T
Possible ST normal Possible T wave
Changes inversion (hours) Q waves
depression inversion
(days)

ST elevation criteria:

• >1mm in limb leads and >2mm in chest leads

Cardiac Enzymes:

• Troponin

• CK-MB

• Myoglobin

• SGPT/SGOT levels

• LDH levels

• Other causes of troponin increase: Congestive cardiac failure

SCORING SYSTEM
GRACE Scoring

• Predicts 6/12 mortality in NSTEMI patients

• Age

• HR and systolic BP
 • Killip class (CCF, pulmonary edema, shock)

• Cardiac arrest on admission

• Elevated cardiac markers

• ST segment change

TIMI Score

• Risk of cardiac events in next 30 days

• Age >65

• Known coronary artery disease

• Aspirin in last 7/7

• Severe angina (>2 in 24hr)

• ST deviation >1mm

• Elevated troponins

• >CAD risk factors

TREATMENT ALGORITHM

Treatment of acute coronary syndrome.

• Check for patency of airway, breathing, and circulation

• Drugs used: Mnemonic MONA

◦ Morphine

◦ Oxygen (as needed)

◦ Nitrates - GTN spray

◦ Aspirin – 300 mg chewed

◦ Antiemetics

• In case of Unstable angina or NSTEMI

◦ Low molecular weight heparin – Enoxaparin (1 mg/kg) or Fondaparinux

(2.5 mg)

◦ Statins – Atorvastatin (80 mg) or Rosuvastatin (40 mg)

◦ Beta blocker – Metoprolol or Propranolol

• In case of STEMI

◦ If PCI facility is available and PCI can be done within 120 minutes of onset
of disease, PCI is preferred

◦ If PCI cannot be done, thrombolysis is done using Alteplase, Tenecteplase,

Streptokinase, Urokinase

• Long-term management

◦ Aspirin – 75/150 mg

◦ Clopidogrel – 75/150 mg

◦ Beta-blocker – Metoprolol

◦ ACE inhibitors

◦ Statins – High dose

◦ Heparin/LMWH – five days

◦ Modification of risk factors

Prescription for long-term management:

Drug Dosage Frequency

Aspirin 75 mg O.D.

Clopidogrel 75 mg O.D.

Atorvastatin 40-80 mg O.D.

Metoprolol 25 mg B.I.D.

Enalapril 5 mg O.D.

Thrombolysis
• Indications

◦ STEMI

◦ New onset LBBB

• Contraindications of thrombolysis:

Absolute Relative
History of cerebrovascular hemorrhage anytime in
Current use of anticoagulants (INR ≥2)
life

History of non-hemorrhagic stroke or any other Recent (<2 weeks) invasive or surgical
cerebrovascular event within the past 1 year procedure, prolonged (>10 min) CPR

Uncontrolled marked hypertension (systolic BP

>180 mm Hg, diastolic BP >110 mm Hg). Known bleeding diathesis
However, Streptokinase can be given
Recent trauma (including traumatic
Suspected aortic dissection
resuscitation)
Active internal bleeding (excluding menstruation) Pregnancy
Known intracranial aneurysm/AV malformation/
Hemorrhagic ophthalmic condition
neoplasm (primary or metastatic)
Intracranial/spinal surgery within last 3 months Active peptic ulcer disease
History of severe hypertension that is
currently controlled
Thrombolytic Agent & Dose

Thrombolytic Agent Dose

Alteplase (tissue 15 mg bolus followed by 50 mg intravenously over the first 30 minutes
plasminogen activator - followed by 35 mg over the next 60 mins
Streptokinase (STK) 1.5 million units (MU) intravenous infusion over 1 hour
Tenecteplase (TNK) Given as a single weight-based intravenous bolus of 0.53 mg/kg over
Double-bolus regimen consisting of a 10 MU bolus given over 2-3
Reteplase (rPA)
minutes, followed by second 10 MU bolus 30 minutes later

Signs of reperfusion

• Immediate relief of chest pain

• Reduction of the initial ST-segment elevation by 50% within 60-90 minutes of

fibrinolytic therapy

• Onset of reperfusion arrhythmias (e.g., accelerated idioventricular rhythm and

frequent ventricular ectopics)

• Early peaking of CK-MB enzyme

Complications of thrombolytic therapy

• Hemorrhage – Major complication

• Allergic reactions – These may develop with use of Streptokinase and Urokinase

• Hypotension – It may develop if Streptokinase is infused rapidly

Percutaneous Intervention (PCI)

• Indications: Patients with STEMI with following features:

◦ Symptoms of ischemia of less than 12 hours duration

◦ Symptoms of ischemia of less than 12 hours duration who have

contraindications to fibrinolytic therapy, irrespective of the time delay from
first medical contact

◦ Cardiogenic shock or acute severe heart failure (HF), irrespective of time

delay from MI onset

• Door-to-balloon time is ≤ 90 minutes.

• Door-to-balloon time minus door-to-needle time is ≤ 1 hour.

Rescue PCI: Combination of PCI with thrombolytic therapy

• PCI is performed within 12 hours after failed thrombolysis/fibrinolysis for patients

with continuing or recurrent myocardial ischemia.
 • Indications: STEMI in patients who have received fibrinolytic therapy and have
cardiogenic shock, severe congestive heart failure (Killip class III), or
hemodynamically compromising ventricular arrhythmias.

• It may be performed in patients with symptoms of persistent ischemia.

Coronary Artery Bypass Graft (CABG)

• Indications:

◦ Multiple vessels are blocked

◦ Refractory case

◦ Failed PCI

◦ Patients with STEMI at the time of operative repair of other mechanical

defects

Complications of ACS

• Mnemonic: Spared

◦ Sudden death

◦ Pericarditis

◦ Aneurysm/Arrhythmia

◦ Ruptured Ventricular wall

◦ Embolism

◦ Dressler’s syndrome
Systolic Murmurs

Murmur and Description Example

- VSD (small muscular VSD/large VSD with
Early systolic Murmurs (begin with the first
pulmonary hypertension) - Acute severe MR -
heart sound and extend to middle or late systole)
Acute severe TR
Mid Systolic/Ejection systolic murmurs
(begin following a murmur-free interval in early - Aortic stenosis - Pulmonary stenosis -
systole and end with a murmur-free interval (of HOCM
variable duration) in late systole
Late Systolic Murmurs (begin during the last
- Mitral valve prolapse - Tricuspid valve
half of systole and may or may not extend to the
prolapse - Papillary muscle dysfunction
second heart sound)

Pansystolic murmurs (begin with the first - Mitral regurgitation - Tricuspid regurgitation
heart sound and extend to or through the second - Ventricular septal defect - Rare – Early
heart sound) PDA/PDA with Eisenmenger

Diastolic Murmur
Murmur Example

Early diastolic
- Aortic regurgitation - Pulmonary regurgitation
Murmur

- Mitral stenosis - Tricuspid stenosis - Carey Coombs murmur of acute

rheumatic fever - Austin Flint murmur of chronic aortic regurgitation - Flow
Mid diastolic
MDM - Across mitral valve – MR, AR, VSD, PDA - Across tricuspid valve –
murmur
ASD, TR, TAPVC - Atrial myxoma - Ball-valve thrombus - Cor triatriatum -
Rytand murmur of complete heart block

Late diastolic
murmurs/
- Mitral stenosis - Tricuspid stenosis - Myxoma
presystolic
murmur

Continuous Murmurs

• Systemic to pulmonary communication

◦ Patent ductus arteriosus

◦ Aorto pulmonary window

◦ Anomalous origin of left coronary artery from pulmonary artery (ALCAPA)

◦ Tricuspid atresia
 ◦ Truncus arteriosus

◦ Shunts for TOF surgery – Waterson, Potts, or Blalock-Taussig shunt

• Systemic to right heart connection

◦ Coronary AV fistula

◦ Rupture sinus of Valsalva

• Left atrium to right atrium connection

◦ Lutembacher syndrome

• Arteriovenous fistula

◦ Systemic

◦ Pulmonary

• Normal Flow through Constricted Arteries

• Coarctation of aorta

• Peripheral pulmonary stenosis

• Renal artery stenosis

Increased Flow through Normal Vessels

• Venous

◦ Cervical venous hum

◦ Cruveilhier-Baumgarten murmur

• Arterial

◦ Mammary souffle

◦ Uterine souffle

◦ Thyrotoxicosis

◦ Tumors – hepatoma, hypernephroma

The pharmacologic interventions used most commonly in clinical practice are amyl nitrate
administration and intravenous administration of alpha-agonists (phenylephrine or
methoxamine).

Valvular
Accentuated by
disease

MS Expiration- Exercise, Squatting, Amyl Nitrate, isometric hand grip

MR Expiration- Squatting, Isometric Exercise

Expiration- Post PVC beat squatting ,Lying flat from standing, Inspiration,
AS
Sudden standing ,Valsalva, Amyl Nitrate, Valsalva, Standing, Handgrip

Valvular
Accentuated by
disease

Expiration, Sitting up and leaning forward, Squatting, Isometric

AR
exercise ,Vasopressors

Murmur and click later If LV Volume increase -Squatting, Post

MVP
ectopic ,Isometric Exercise (intensity increases)

Valvular disease Accentuated by

Expiration, Valsalva strain ,Standing, Post ectopic,
HOCM
Amyl nitrate
Amyl Nitrate, Valsalva
Murmur and click Earlier if LV Volume decrease
Standing, Valsalva ,Inspiration ,Sustained
Handgrip ,Squatting, Methoxamine

NAMED MURMURS

Murmur Description
Carey Coombs
Mid diastolic murmur, in rheumatic fever
murmur
Austin Flint
Mid-late diastolic murmur, in Aortic Regurgitation.
murmur
Graham-Steel
High pitched, diastolic, in pulmonary regurgitation
murmur
Rytands murmur Mid diastolic atypical murmur, in Complete heart block.
Diastolic murmur, Left Anterior Descending (LAD) artery
Docks murmur
stenosis
Mill wheel
Due to air in RV cavity following cardiac catheterization
murmur
Inferior aspect of lower left sternal border, systolic ejection
Stills murmur sound, vibratory/musical quality, in subaortic stenosis,
small VSD
Gibson’s murmur Continuous machinery murmur of PDA
Diastolic murmur of aortic regurgitation. Hodgkin
Key-Hodgkin
correlated this diastolic murmur with retroversion of the
murmur
aortic valve leaflets, seen in syphilitic aortic regurgitation
Diastolic murmur heard best at the left sternal border.
Cabot-Locke
Heard in anemic patients. The murmur resolves with
murmur
treatment of anemia.
It is the loud pansystolic murmur which is heard
Roger’s murmur
maximally at the left sternal border in small VSD.
Pontains murmur Cervical venous hum in severe anemia

DYNAMIC AUSCULTATION

Venous return/
Afterload Drugs
preload
Decrease
Increase (Leg Decrease (Valsalva/ Increase
(Amyl Diuretic ACEIs
raise/Squat) Standing) (Handgrip)
nitrate)
Yes, but
MS, AS ↑ ↓ ↓ (AS) ↑ (AS)
better
AS
(Replace)
Negligible effects in MS ✗
MS( ballo
on)
MR,
↑ ↓ √
AR
VSD ↑ ↓ ↑ ↓ √

HOCM ↓ ↑ ↓ ↑ ✗ ✗

MVP ↓ ↑ ↓ ↑ ✗ ✗

MITRAL STENOSIS
• Pulse: Low volume irregular

• BP: Low
 • JVP: ↑RHF, TR-CV Prominent, AF-absent a

• Apex: Tapping

• PSH: +++

• Other: Diastolic thrill in apex

• S1: Loud

• S2: P2-Loud

• S3: RV

• S4: X

• Other sounds: OS

• Murmur: MDM with PSA, P-ESM or EDM

MITRAL REGURGITATION
• Pulse: High volume irregular

• BP: Wide PP

• JVP: ↑RHF, TR-CV Prominent, AF-absent a

• Apex: Hyperdynamic

• PSH: +++

• Other: --

• S1: Loud

• S2: P2-Loud

• S3: LV

• S4: Acute MR

• Other sounds: NIL

• Murmur: PSM in mitral area radiating to axilla

AORTIC STENOSIS
• Pulse: Low volume parvus et tardus
 • BP: Systolic decapitation

• JVP: Normal

• Apex: Heaving

• PSH: --

• Other: --

• S1: Normal

• S2: A2-Soft in valvular, loud in supravalvular

• S3: LV

• S4: Acute MR

• Other sounds: AEC

• Murmur: ESM conducted to carotid, Gallavardin phenomena

AORTIC REGURGITATION

• Pulse: High volume collapsing

• BP: Wide PP

• JVP: Normal

• Apex: Hyperdynamic

• PSH: --

• Other: --

• S1: Soft

• S2: A2-Soft in valvular, loud in root dilated

• S3: LV

• S4: Acute

• Other sounds: OS

• Murmur: EDM in the aortic area or Neo aortic area

ASD

• Pulse: Normal

• BP: Normal

• JVP: Normal

• Apex: Normal

• PSH: +++

• Other: --

• S1: Loud

• S2: P2 Loud - Wide Fixed Split

• S3: RV

• S4: RV

• Other sounds: --

• Murmur: TR or PR Murmurs

HEART FAILURE
It is a clinical syndrome that develops when the heart is not able to meet the demand, hence
causing a decrease in cardiac output.

Signs and Symptoms:

• Low cardiac output

• Pulmonary venous congestion

• Systemic venous congestion

A pathophysiological process in which the heart, as a pump, is unable to meet the

metabolic requirements of the tissues for oxygen and substrates, despite the venous return to
the heart being either normal or increased.

INTRODUCTION

• It results from any structural or functional cardiac disorder.

• If it also involves a volume overload → Congestive cardiac failure.

 • Common end-stage of many forms of chronic heart disease.

• Most common reason for hospitalization in adults >65 years of age.

• Can be due to cumulative effects of chronic work overload (valve disease or

hypertension) or ischemic heart disease (e.g., following MI with heart damage) or
acute hemodynamic stresses, such as fluid overload, sudden valvular dysfunction,
or myocardial infarction, leading to sudden heart failure.

PATHOPHYSIOLOGY

Normally, cardiac output is determined by:

• Preload → Volume and pressure of blood in ventricles at the end of diastole.

• Afterload → Volume and pressure of blood in ventricles during systole.

• Myocardial contractility → Depends on adrenergic nervous system activity and

levels of circulating catecholamines.

Index Event

• Damages the heart muscle (with loss of functioning cardiac myocytes).

• Disturbs myocardial ability to generate force (prevents heart from contracting

normally).

Progressive disorder, beginning with an initial index event, followed by added insults to the
heart.

The common feature of these events is a decrease in the pumping capacity of the heart.

Compensatory mechanisms:

• Tachycardia

• Increased myocardial contractility

• Catecholamine activation (neurohumoral systems)

If heart failure progresses, the compensatory mechanisms become overwhelmed and turn
pathological, leading to Progressive Heart Failure, commonly associated with fluid retention
and sodium retention.

Heart failure is the common end stage of many forms of chronic heart disease.
 Low-output Heart Failure High-output Heart Failure
Failure of the heart to maintain circulation despite
Systolic Heart Failure → Decreased cardiac
increased cardiac output. Causes: hyperthyroidism,
output, decreased left ventricular ejection
anemia, pregnancy, AV fistulae, beriberi, Paget’s
fraction.
disease.
Diastolic Heart Failure → Elevated left and
right ventricular end-diastolic pressures, may
have normal left ventricular ejection fraction.

Diastolic and Systolic Dysfunction

Systolic Dysfunction Diastolic Dysfunction

Characterized by an abnormality Characterized by impaired ventricular relaxation and

of ventricular contraction. increased ventricular stiffness, resulting in reduced filling.

Ejection fraction is usually below

40%.
Causes: Coronary artery disease, Causes: Hypertension, coronary artery disease, hypertrophic
hypertension, valvular heart obstructive cardiomyopathy (HOCM), restrictive
disease. cardiomyopathy.

ACUTE AND CHRONIC HEART FAILURE

Acute Heart Failure Chronic Heart Failure

Rapid development of heart disease. Slow development of heart disease.

Causes: MI, valvular heart disease, infective Causes: Hypertension, valvular heart disease,
endocarditis. cardiomyopathy.

Onset of Failure

• Acute Heart Failure: Sudden development of heart failure, leading to a sudden fall
in cardiac output with hypotension, without peripheral edema. Can develop de novo
or as acute decompensated event (acute-on-chronic).

• Chronic Heart Failure: Gradual development of heart failure with maintained

systemic arterial pressure but edema development.
 • Compensated Heart Failure: Condition in which compensatory mechanisms
prevent heart failure development. Severe or acute failure can be triggered by minor
insults (e.g., infection, atrial fibrillation).

Anatomical Classification

Left Ventricular Failure

• Most common type of heart failure.

• Most common cause: ischemic heart disease, hypertension, MR, AS, AR, HCM.

• Reduction in left ventricular output.

• Increase in left atrial and pulmonary venous pressure.

• Acute increase produces pulmonary congestion or pulmonary edema (MI).

• Eventually leads to right-sided heart failure.

Right Ventricular Failure

• Reduction in right ventricular output.

• Increase in right atrial and systemic venous pressure.

• Mostly caused by Left-sided heart failure.

• Causes of isolated right heart failure:

◦ Chronic lung disease (cor pulmonale)

◦ Tricuspid and pulmonary valvular stenosis

Biventricular Failure

• Characterized by failure of the ventricles of both the left and right heart.

• Dilated cardiomyopathy or ischemic heart disease affects both ventricles.

• Disease of the left heart leads to chronic elevation of the left atrial pressure,
pulmonary hypertension, and leading to right heart failure.
Reduced Ejection Fraction (<40% HFrEF) vs. Preserved Ejection Fraction (>50%)

HFrEF (<40%) HFpEF (>50%)

Coronary artery disease: Myocardial
Pathologic hypertrophy
infarction, ischemia
Chronic pressure overload: Hypertension, High output states: Metabolic disorders
obstructive valvular disease (MS, TS), (thyrotoxicosis), Nutritional disorders (beri
endomyocardial fibrosis beri), Chronic anemia
Chronic volume overload of ventricle:
Regurgitant valvular disease (MR, AR), Restrictive cardiomyopathy
left-to-right shunts (VSD, ASD, PDA)
Chronic lung disease: Cor pulmonale,
Aging
pulmonary vascular disorders
Non-ischemic dilated cardiomyopathy -
Chagas disease
Toxic/drug-induced damage

• Heart failure with mid-range EF (HFmrEF): EF 41-49%

• Most common causes: Ischemic heart disease, hypertensive heart disease

Risk Factors

Risk Factors

Hypertension

Diabetes mellitus

Hyperlipidemia

Coronary artery disease

Use of cardiotoxic substances (alcohol, tobacco,
cocaine)

Symptoms
• Exertional dyspnea, Orthopnea

• Paroxysmal nocturnal dyspnea (PND)

• Cardiac asthma (PND equivalent) - nocturnal cough, characterized by wheezing

(secondary to bronchospasm), due to acute pulmonary edema

• Bendopnea

• Cheyne-Stokes respiration
 • Nocturia (Early heart failure: Renal perfusion and diuresis are better at night when
patient is supine)

• Cerebral symptoms:

◦ Confusion, difficulty in concentration, impaired memory

◦ Headache, insomnia, anxiety (arterial hypoxemia and reduced cerebral

perfusion)

• Nonspecific symptoms:

◦ Fatigue due to low cardiac output and weakness due to decreased perfusion of
skeletal muscles

◦ Low-grade fever due to reduction of cutaneous blood flow

◦ Anorexia, nausea, abdominal fullness/pain due to congestion of liver and portal

venous system

Summary
• Fluid overload in both systemic and pulmonary systems

◦ Pulmonary: Dyspnea, PND, Crepitation, Pleural effusion

◦ Peripheral: Pedal edema, Low cardiac output

Signs

• Dependent/cardiac edema

◦ Due to gravity, fluid accumulates over dependent parts of the body

◦ Ambulatory patients: Symmetrically in both legs - pretibial region, around

ankles (worse in evening)

◦ Bedridden patients: Sacral region

• Anasarca: Advanced heart failure, fluid accumulates throughout the body (Face and
upper limbs spared until terminal stages)

• Cyanosis: Lips, nail beds. Extremities appear cold and pale due to reduced blood flow

◦ Central cyanosis: Due to pulmonary edema

◦ Peripheral cyanosis: Due to low cardiac output

• Pulse: Volume is reduced, pulsus alternans (severe cases)

Blood Pressure

• Reduced pulse pressure due to reduced stroke volume

• Mild elevation of diastolic blood pressure due to generalized vasoconstriction

• Profound hypotension in acute heart failure

Jugular Venous Pressure (JVP)

• Elevated JVP due to raised right-sided pressure

• JVP may not be raised at rest during early stages of heart failure

Third and Fourth Heart Sounds

• Third heart sound (S3): Highly suggestive of heart failure

◦ Right ventricular: Heard at Tricuspid

◦ Left ventricular: Heard at Mitral

• Fourth heart sound (S4): Seen in hypertensive heart disease

• Triple/quadruple/summation gallop seen

Framingham criteria for diagnosis of heart attack

The diagnosis of heart failure should not be made based on history and clinical findings
alone.

Criteria for diagnosis of heart failure: one major + two minor.

Major

• Paroxysmal nocturnal dyspnea

• Distension of neck vein

• Rales

• Cardiomegaly

• Acute pulmonary edema

• S3 gallop

• Increased venous pressure (>16 cm H₂O)

• Positive Abdominal jugular reflux

• Weight loss >4.5 kg over 5 days treatment. (Diuresis)

Minor

• Extremity edema

• Night cough

• Dyspnea on exertion

• Hepatomegaly

• Pleural effusion

• Vital capacity reduced by one-third from normal

• Tachycardia (>120 beats per minute)

INVESTIGATION

Chest X-Ray:

• Cardiomegaly.

• Pleural effusion - Bilateral or unilateral.

• Phantom tumor - Fluid in horizontal or oblique fissures of lungs (which disappears

after treatment with diuretics).

• Bat’s wing appearance: Hazy opacification spreading from the hilar regions on both
sides.

Electrocardiography:

• Previous MI, active ischemia, ventricular hypertrophy (e.g., due to hypertension), atria
abnormality, arrhythmias, and conduction abnormalities (e.g., arrhythmia).

Brain natriuretic peptide (BNP) or N-terminal portion of proBNP (NTproBNP)

• It is elevated in heart failure and highly sensitive for the diagnosis.

• It is a marker of risk (>100 pg/mL) and is useful in the investigation of patients with
breathlessness or peripheral edema (to differentiate cardiac from respiratory cause of
acute dyspnea).
Invasive hemodynamic monitoring:

• Useful in selected patients with acute heart failure who have persistent symptoms in
spite of empiric standard therapies.

• Done prior to cardiac transplant to look for any changes.

• Criteria to diagnose heart failure

COMPLICATIONS

Renal failure

• Cardiorenal syndrome (poor renal perfusion due to low cardiac output) may be
worsened by therapy Diuretics ACE, and ABRs.

Hypokalemia

• As a result of potassium-losing diuretics or hyperaldosteronism produced by activation

of the renin-angiotensin system and impaired aldosterone metabolism due to
congestion of liver.

Hyperkalemia

• Due to the effects of drugs which promote renal resorption of potassium (e.g.
combination of ACE inhibitors or angiotensin receptor blockers, and mineralocorticoid
receptor antagonists).

Hyponatremia

• May develop in severe heart failure and is a poor prognostic sign.

• May be due to diuretics, inappropriate retention of water (due to high ADH secretion),
or failure of the cell membrane ion pump.

Hepatic dysfunction

• Due to hepatic venous congestion and poor arterial perfusion.

Thromboembolism

• Deep vein thrombosis and pulmonary embolism due to low cardiac output and
immobility.

• Systemic emboli in AF or AFI, or intracardiac thrombus complicating - MS, MI or left

ventricular aneurysm.

Arrhythmias

• Very common. Due to dyselectrolytemias, underlying heart disease or pro-arrhythmic

sympathetic activation.

• Atrial fibrillation (20%).

• Sudden death (50%) due to a ventricular arrhythmia, ventricular ectopic beats, and
non-sustained ventricular tachycardia.
GENERAL LIFESTYLE ADVICE/MEASURE

Treatme
Education Prevent HF nt of Diet Physical activity Bed rest
cause
Good general
nutrition and
maintain
desired
weight and
body mass
Cessation of
index Reduced the
smoking and
Avoid large demands on the
illicit drugs
meals, foods heart
Control of
rich in salt or Regular low level Bed rest for a few
hypercholest
added salt endurance exercise days is for patients
erolemia
Wheneve Diet low in reverses with exacerbations
Explanation Pharmacolog
r possible fat, rich in ‘deconditioning’ of of congestive
of nature of ical
to prevent fruit and peripheral muscle cardiac failure
disease, treatment
progressi vegetables, metabolism and is Prolonged bed rest
causes and following
on to and increase advisable in patients may predispose to
treatment of myocardial
heart fiber with compensated deep vein
heart failure infarction
failure Fluid heart failure thrombosis
Identify and
restriction Avoid strenuous Avoided by daily
treat any
(<1.5L) in isometric activity leg exercise, low-
factor that
severe HF dose subcutaneous
aggravates
Alcohol heparin and elastic
the heart
should be support stocking
failure
avoided
Omega-3
PUFAs
reduces
mortality and
admission

DRUG THERAPY/MANAGEMENT

• Function of heart can be improved by increasing contractility, reducing preload or

afterload.

• Drugs that reduce preload are used in patients with high end-diastolic filling pressures
and pulmonary or systemic venous congestion.

• Drugs that reduce afterload or increase myocardial contractility are used in patients
with signs and symptoms of a low cardiac output.
Diuretic Therapy

• Increase urinary excretion of salt and water leading to reduction in blood and plasma
volume.

• Reduce preload and improve pulmonary and systemic venous congestion.

• May also reduce afterload and ventricular volume and increase cardiac efficiency.

Loop diuretics: Furosemide 20-40 mg once or twice

Thiazide diuretics: Hydrochlorothiazide 25 mg once or twice, or metolazone 2.5-5 mg OD.

• In severe heart failure, the combination of a loop and thiazide diuretic may be needed.

• Regular monitoring of serum electrolytes and renal function is necessary because of

the risk of hypokalemia and hypomagnesemia.

• Mineralocorticoid receptor antagonists (spironolactone, 12.5-25 once or twice) are

potassium-sparing diuretics and are beneficial in patients having heart failure with
severe left ventricular systolic dysfunction.

Angiotensin-converting Enzyme Inhibitor (ACEI) Therapy

• Improve survival in patients in all functional classes (NYHA I - IV) and are given to
all patients at risk of developing heart failure.

• They improve effort tolerance and mortality and prevent the onset of overt heart failure
in patients with asymptomatic heart failure following myocardial infarction.

Flowchart:

• Prevent the conversion of angiotensin I to angiotensin II

• Prevents peripheral vasoconstriction, activation of sympathetic system and salt-water

retention due to aldosterone

• Interrupts neurohumoral activation

• Also prevent the undesirable activation of RAAS due to diuretics

Initiation:

• Start low dose; if tolerated then gradual increase in few days to weeks to target dose or
maximum tolerable dose.

• Monitor blood pressure, Serum creatinine and potassium.

Drugs and dosage:

• Captopril (6.25 mg thrice till 50 mg thrice a day)

• Enalapril (2.5 mg twice to 10-20 mg twice a day)

• Lisinopril (2.5-5 mg once to 20-40 mg once a day)

• Ramipril (1.25-2.5 mg once till 10 mg once a day)

Angiotensin II Receptor Antagonists

Indications: Second line therapy in patients intolerance of ACEI or alternative to ACEI.

Drugs and dosage:

• Losartan (25-50 mg once till 50-150 mg once a day),

• Valsartan

• Telmisartan

• Olmesartan (20-40 mg twice till 160 mg twice).

• Same initiation and monitoring as ACEI and titration by doubling the dose.

Aldosterone Receptor Antagonists

Indications:

• NYHA II-IV

• EF <35%

• Improve survival in patients with heart failure.

Dose: Spironolactone 12.5-25 mg once till 50 mg daily.

Monitoring:

• Stop all K+ supplements, check K+ and creatinine 2-3 days after starting then one
week and every month for 3 months and every 3 months and when clinically indicated.

Side effects: Increase K+ (10-15%), gynecomastia or breast pain.

Beta-adrenoceptor Blockers

Indications:
 • To all patients with current or prior HF and a Left Ventricular EF <40% (HFrEF) in the
absence of a contraindication.

• Start low and increased gradually over a 12-week period even during hospitalization.

Drugs and dosage:

• Bisoprolol (1.25-2.5 mg once till 10 mg once)

• Carvedilol (3.125 twice till 50 mg twice)

• Metoprolol succinate (12.5 once till 200 mg once)

Vasodilators-nitrate Combination (Hydralazine-Nitrate)

• Given orally and intravenously.

• Reduces afterload and preload.

• Use is limited by pharmacological tolerance and hypotension.

Indication:

• NYHA III-IV

• Low EF on ACEI and BB intolerant or contraindication of ACEI or ARA (e.g., in

severe renal failure).

Dose: 37.5 mg hydralazine and 20 mg isosorbide dinitrate start one-tab TID to increase till 2
tabs TID.

DIGOXIN (Cardiac glycoside)

• Cardiac glycoside is used in patients with Atrial Fibrillation with heart failure.

• Usual dose 0.125-0.25 mg 5 days a week (Not every day due to digoxin toxicity).

• Digoxin toxicity- nausea, vomiting, xanthopsia and heart block.

• Maintain 5-0.9 ng/dL plasma concentration (narrow therapeutic range).

Ivabradine

• Acts on Funny or I(f) inward current, in SA node and reduces the heart rate.

• Best given to patients who cannot take β-blockers or in whom the heart rate remains
high despite β-blockade.
Anticoagulation therapy:

• Indicated in patients with heart failure who are at risk for thromboembolism- atrial
fibrillation, valvular heart disease, documented left ventricular thrombus or a history of
embolic stroke.

NEWER AGENTS IN HEART FAILURE MANAGEMENT

SGLT 2 Inhibitors

• Sodium glucose transporters in kidney and GUT

• It produces diuresis and natriuresis.

• It is used for diabetes.

Angiotensin receptor neprilysin inhibitor

Sacubitril valsartan for NYHA Class II to IV heart failure with reduced ejection fraction.

DEVICES

Implantable Cardioverter Defibrillator (ICD)

• Symptomatic ventricular arrhythmias and heart failure have a very bad prognosis.

• Irrespective of their response to anti-arrhythmic drug therapy, implantation of a cardiac

defibrillator improves survival

• Indicated in nonischemic or ischemic heart disease (at least 40 days post-MI) with
LVEF of <35% with NYHA class II or III symptoms or NYHA I with EF <30% on
chronic medical therapy, who have reasonable expectation of meaningful survival for
more than 1 year.

Ventricular Assist Device (VADs)

• There is limited supply of donor organs and VADs take over pumping for the
ventricles.

• VADs are used as

◦ Bridge to cardiac transplantation,

◦ Potential long-term therapy,

◦ Short-term restoration therapy following a potentially reversible insult (e.g.,

viral myocarditis).
NEWER DRUGS

Nesiritide (Recombinant analogue of BNP)

• Actions:

◦ Increase natriuresis, diuresis, and cardiac index.

• Reduce pulmonary capillary wedge pressure, pulmonary artery pressure, pulmonary

vascular resistance, and systemic blood pressure in a dose-dependent manner.

• Reversal of the deleterious neurohormonal response associated with heart failure.

• Reduces levels of endothelin-1, aldosterone, and norepinephrine.

Advantages: Does not require ICU admission or invasive monitoring, lower incidence of
tachycardia and proarrhythmic effects, and lesser the need for supportive therapies such as
diuretics.

Endopeptidase inhibitor: Inhibits ACE + neutral peptidases (Omapatrilat).

Calcium sensitizer: Levosimendan, novel agent with inotropic properties developed

specifically for the management of ADHF (acute decompensated heart failure). It acts by
sensitizing troponin C to calcium.

Endothelin receptor antagonist: Bosentan, tezosentan. Effective in acute coronary

syndromes, acute renal failure, and acute heart failure. Indirectly improves contractility
while decreasing pulmonary capillary wedge pressure.

Vasopressin antagonists (V2 RA): Tolvaptan, lixivaptan, conivaptan.

Used as an adjuvant to diuretic in advanced heart failure.

Enoximone: Type 3 phosphodiesterase inhibitor.

Angiotensin receptor-neprilysin inhibitor: Sacubitril-valsartan for NYHA class II to IV

heart failure with reduced ejection fraction.

REFRACTORY HEART FAILURE

• Optimal ‘triple therapy’ for patients with chronic congestive heart failure (CHF)
includes diuretics, digoxin, and either angiotensin-converting enzyme inhibitors
(ACEI) or hydralazine + nitrates combination.

• Symptoms of CHF at rest or repeated exacerbations of CHF despite ‘optimal’ triple-

drug therapy.
 • Management: It is managed as end-stage heart failure, i.e., stage D. Novel agents and
nonpharmacological agents can be tried.

SLE (Systemic Lupus Erythematosus)

A multisystem autoimmune disorder targeting various organs.

• Genetic Susceptibility:

◦ Gene deficiency of C1q, C2, C4 (complement system)

◦ HLA - D2, 3, 8

◦ Fcr 2A, 3A 2B

• If detected early, good prognosis with treatment.

• Once Renal or Neural system is involved, prognosis worsens.

PATHOGENESIS

• Normally, after cell apoptosis, the cellular remnants carrying self-antigen are hidden
from the immune system.

• In SLE, the removal of remnants by phagocytes is inefficient which are then

transferred to Lymphoid tissuewhich then come in contact with B cells to produce
antibodies.

• These antibodies form Antibody Immune complexes which will target the normal
functioning cells of various systems of the body.

CLINICAL FEATURES
A. Fatigue
B. Fever
C. Weight loss
D. Malaise
E. Skin:

• 80-95% patients present with dermatological features

• Butterfly rash/Malar Rash

• Discoid Lupus

• Maculopapular rash

Vasculitis skin lesions and unhealing ulcer

F. Oral ulcers
G. Photosensitivity
H. Scarring Alopecia
I. Livedo Reticularis (Lace-like pattern of cutaneous vessels on leg)
J. Vasculitis
K. Panniculitis including erythema
L. Palpable papule
M. Raynaud’s phenomenon

NERVOUS SYSTEM MANIFESTATIONS

• 60% cases affected

• Features:

◦ Seizures

◦ Stroke (due to vasculitis)

◦ Cerebral ataxia

◦ Polyneuropathy

◦ Multiple cranial nerve involvement

◦ Psychosis or depression

◦ Headaches

◦ Aseptic meningitis

EYE MANIFESTATIONS

• Vasculitis of Retina

• Episcleritis

• Secondary Sjogren’s

• Conjunctivitis
 • Optic neuritis

GI MANIFESTATIONS

• Oral ulcers (painless unless infected)

RESPIRATORY MANIFESTATIONS

• Pleural effusion

• Acute:

◦ Acute lupus pneumonitis

◦ Acute pulmonary hemorrhage

◦ Chronic diffuse interstitial lung disease

HAEMATOLOGICAL MANIFESTATIONS

• Anemia

• Leukopenia

• Elevated ESR

• Normal CRP (elevated CRP is indicative of infection)

• Reduced Complements (C3, C4 in case of active disease)

• Thrombocytopenia

• Pancytopenia

AUTO ANTIBODIES

Antibody Disease Prevalence

Ds DNA SLE 70%
Anti-histone Drug-induced Lupus -
Anti-centromeric Limited SS 70%
SLE 40-60%
Anti-Ro (SS-A)
Primary Sjogren’s 60-90%

SLE 15%
Anti-La (SS-B)
Primary Sjogren’s 35-85%
 10-25% in Caucasian, 30-50% in
Anti-Sm SLE
African
Anti-UI-RNP SLE
30%
Overlap syndrome
Anti-JO (Anti- Polymyositis 30%
Anti-topoisomerase 1 Dermatomyositis, Diffuse
30%
(Scl-70) cutaneous SSc

DIAGNOSTIC CRITERIA

Criteria of the American College of Rheumatology for classification of SLE

(4 out of the following should be present to diagnose it as SLE)

1. Malar rash (Butterfly rash)

2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
◦ a. Pleuritis

◦ b. Pericarditis

7. Renal disorders
◦ a. Proteinuria (>0.5 g/24 hr or 3+, persistently)

◦ b. Cellular casts
8. Neurological disorders
◦ a. Seizures

◦ b. Psychosis
9. Hematological manifestations
◦ a. Hemolytic anemia
◦ b. Leukopenia

◦ c. Lymphopenia

◦ d. Thrombocytopenia
10. Immunological disorder
◦ a. Raised antinative DNA Antibody binding

◦ b. Anti-Sm antibody

◦ c. Positive finding of antiphospholipid antibodies

◦ d. Antinuclear antibody in raised titre

  Pulmonary Embolism:

 Pathophysiology:

1. Dislodgement of blood clot

 Lower Limb
 Pelvic vein
 Renal vein
 Upper extremity
 Right heart
2. Spontaneous thrombosis

 Risk Factors for PE & DVT:

 Immobilization
 Surgery within last 3 months
 Past history of venous thromboembolism
 Malignancy
 DVT
 Recent travel in last 2 weeks
 Surgery >30 minutes of anesthesia
 Central line
 HD Catheter
 Pacemaker
 Obesity
 Smoking
 Hypertension
 Pregnancy

 Well’s Criteria:

Clinical signs & symptoms of DVT? +3

(Calf tenderness, swelling >3months,
erythema, pitting edema affected leg only)
PE is #1 diagnosis, or equally likely +3
Heart Rate>100 +1.5
Immobilization at least 3 days, or the surgery +1.5
in the previous 4 weeks
Previous, objectively diagnosed PE or DVT? +1.5
Hemoptysis +1
Malignancy w/Rx within 6 months, or +1
palliative?

Score >6: High Risk

Score 2-6: Moderate Risk
Score <2: Low Risk

 P.E. & Malignancy:

 Presenting sign: Pancreatic, prostate, leukemia
 Late sign: Breast, lung, CNS tumour

 Symptoms of P.E.:

 Dyspnea
 Pleuritic chest pain
 Cough with hemoptysis

 Signs of P.E:

 Increased RR
 Increased HR
 Decreased BP
 Hypoxia
 Temperature+/-
 Right heart failure signs: RVS4, RVS3, Crepitations

 Signs of Massive P.E:

 Circulatory Collapse
 Acute Cor pulmonale
 Systolic BP <90 mm Hg
 Increased JVP
 RVS3
 RVS4

 P.E & Leg Symptoms:

Asymptomatic: Majority patients don’t have any symptoms

 Lab & Radiologic Findings in P.E:

 ABG:
o Type I Respiratory failure
o Hypoxia
o Hypocapnia with respiratory alkalosis
o Systemic Hypotension  Increased lactate  Metabolic Acidosis

 Cardiac:
o Troponin
o BNP (Brain Natriuretic Peptide)
 D-dimer:
 ECG:

o Sinus tachycardia
o RV Strain
o S1Q3T3
o Right Axis Deviation- Right Atrial Enlargement
 o New onset RBBB

 CXR:

o Normal majority of times

o Atelectasis
o Pleural effusion
o Cardiomegaly
o Hampton’s Lumps
o Westmark’s Sign
o Palla’s Sign

 Angiography: CT Pulmonary
 Ventilation Perfusion Scan
 Lower extremity Ultrasounds
 Pulmonary angiograph: Gold Standard
 CT Pulmonary Angiograph (CT-PA)

 Echocardiogram:
o RV strain
o Increased RV size
o Tricuspid Rejection
o Decreased RV Ejection Fraction
o Thrombus
o Regional wall motion abnormality: Mc Connell Sign- S1Q3T3 on
ECG

 Treatment of P.E:
 Assessment of ABC
 O2 supplementation/ mechanical ventilation needed sometimes
 Hemodynamically compromised  Give vasopressors
 RV failures – IV fluids
 Thrombolysis
 Anti-coagulation
 IVC filter

 Anti- Coagulation:

 If suspension is there, then start early & no contraindications like GI bleeds,

recent surgeries, IC bleeds.

 Heparin:
o Standard Heparin: 80 U/kb bolus followed by 18 U/kg infusion
o Low molecular weight Heparin: 1-1.5 mg BD
o Fondaparinux (monitor aPTT, based on it, adjust the dose of heparin)

 Warfarin/ Coumadin:
o Start early & bridge with Heparin
o Start 5mg or 10 g PO OD
 o INR Target: 2-3

 Newer Agents:

 NOAC:
o Direct Inhibitors of Factor X:
 Apixaban
 Edoxiban
 Rivaroxaban
o Direct Thrombin inhibitor:
 Dabigatran
o LMWH:
 Enoxaparin
 Dalteparin

 Thrombolysis:

 Indications:
o Severe persistent hypertension with hypoxemia with RV dysfunction
& free-floating thrombus on the scan
o CI for anticoagulation
o Active bleeding

 DOC: Streptokinase/ activase

 IVC Filter:

 Indications:
o CI for thrombolysis/ anticoagulation
o Active bleeding
o Recurrent thrombosis/ embolism from legs
o Complication of anti-coagulation: bleed- GI, CNS
o Malignancy: prophylactically IVC filter

 Embolectomy:

 Surgical catheter
 Indication: Severe massive pulmo-embolism, thrombolysis is contraindicated.

 Cardiomyopathy:

Types of
Cardiomyopathy

Primary Secondary

Idiopathic EMF Infective Others

Toxin
 Familial Eosinophilic Metabolic Infiltrative
EMF Autoimmune Deficiency-
related
Dilated/ Only Restrictive Neuromuscular
Hypertrophic Disease
Restrictive
(EMF: Endomyocardial Fibrosis)

 Pathological Types:

1. Hypertrophic Cardiomyopathy

2. Restrictive Cardiomyopathy
 Rigid heart walls & small LV cavity
 Increase in diastolic pressure leading to diastolic heart failure
 Cause: Radiation, Amyloidosis, Sarcoidosis

 Secondary Cardiomyopathy:

Cause Disease
1. Infective  Viral (HIV)
 Fungal
 Bacterial (Syphilis)
 Parasitic
 Protozoal
 Rickettsial
2. Metabolic  Storage diseases
 Mucopolysaccharidoses
 Fabry’s disease
 Hemochromatosis
3. Deficiency  Selenium
 Zinc
 Thiamine
4. Autoimmune  SLE
 Polyarthritis Nodosa
 RA
5. Infiltrative  Amyloidosis
 Sarcoidosis
6. Neuromuscular Disease  Friedreich’s Ataxia
 Myotonic Dystrophy
7. Toxin  Alcohol
 Drugs
 Radiation
8. Takotsubo cardiomyopathy  Features:
 Due to catecholamine excess
 Often seen in women
  Temporary condition due to emotional or
physical stress
 A/k/a Stress Cardiomyopathy or Broken
Heart Syndrome
 Classical Apical ballooning observed
during systole
9. Peripartum cardiomyopathy  Features:
 Predominantly seen during post-partum
phase
10. Noncompaction  Features:
 Embryonic defect
 Massive trabeculation of LV
11. Arrhythmogenic Right  Features:
Ventricular Dysplasia  Common in young children
 More common in Italian origin families
 It can produced sudden cardiac death

 Dilated Cardiomyopathy: (DCM)

 Most common type of cardiomyopathy

 Both ventricular enlargement (Large LV cavity)
 Secondary atrial enlargement
 Ejection fraction (EF) <40%
 Most common Cause: Coronary Artery disease/ IHD (60% cases)
 Other causes: Myocarditis, Alcohol, HIV, Nutritional deficiencies, etc.
 DCM is associated with Anderson disease

 Clinical features of DCM:

1. Features of heart failure:

 S3 Gallop
 JVP
 Peripheral Oedema
 Crepitations
 Cardiomegaly & mitral + tricuspid regurgitation

2. ECG Changes:
 ST changes
 Conduction abnormality
 LBBB

3. Chest X-Ray- Cardiomegaly

4. Echo- Dilated Chambers

 Treatment of DCM: Management of symptoms & heart failure

 Hypertrophic Cardiomyopathy:
 Hypertrophy of ventricles (>1.5 cm) leading to small LV cavity without any other
cause (No Hypertension or aortic stenosis)
 Dynamic LVOT obstruction (Depending upon the volume of ventricle)
 Can be secondary to congenital or acquired hypertrophy
 LV > RV affected
 In children: Ventricular arrythmias & sudden cardiac death

 Differential Diagnosis:

Disease Systolic Murmur on:

Valsalva Squatting
HCM Increases Decreases
Aortic Stenosis Decreases Increases

 Physical Examination:

 Heavy apex
 Triple/ Double apex
 Loud palpable 1st or 4th heart sounds
 Bisferiens Pulse
 Loud systolic murmur on left sternal border

 Diagnosis:

1. ECG: LVH, Dagger waves, Deep T wave inversions

2. CXR
3. Echo
4. Catheterization

 Treatment:

 Aim is to prevent sudden cardiac death & to lower the heart rate
 Drug of choice:  blockers
 Other options: Calcium channel blockers
 Implants: Pacemaker, Implantable cardiac defibrillator
 Surgical myomectomy or Alcohol Ablation of myocardium

 Restrictive Cardiomyopathy:

Primary Causes of RCM Secondary Causes of RCM

1. Loeffler’s Syndrome 1. Amyloidosis
2. EMF 2. Sarcoidosis
3. Idiopathic 3. Radiotherapy
4. Hemochromatosis
5. Glycogen Storage Disease
6. Fabry’s disease
 Cardiac filling is affected with normal systolic function
 Rigid heart walls & small LV cavity leading to reduced diastolic volume
 Increase in diastolic pressure leads to diastolic heart failure
 Causes: Radiation, Amyloidosis, Sarcoidosis, Restrictive EMF
 Predominantly, Right heart involvement leading to Cor Pulmonale

 Clinical features:

1. Dyspnea
2. Pulmonary congestion
3. Predominantly right heart failure

 Diagnosis:

1. ECG: Low voltage complexes

2. Echo: Ventricular hypertrophy, Glistening pericardium
3. Biopsy

 Treatment & Prognosis:

 Poor prognosis
 Diuretics & Digoxin
 Transplant can be used

 Acromegaly:

 Growth hormone (GH) is required for proper growth and development.

 Directly affects metabolism of fat and indirectly effects bone growth.
 Excess secretion of GH prior to closure of epiphyseal growth plates in long
bone before onset of puberty causes pituitary gigantism.
 Excess secretion after puberty causes acromegaly.
 Males and females are equally affected.

 Etiology of Acromegaly:

Excess of growth hormone (GH excess) after puberty may be due to:

o Pituitary tumor (somatotrope pituitary adenoma) is the most common cause.

Acromegaly is caused by growth hormone (GH) secretion usually from a
macroadenoma of pituitary gland.
o Other tumors: Acromegaly is caused by tumors of the pancreas, lungs and
adrenal glands.

 Clinical features: Due to increased GH & IGF-1(insulin-like growth factor 1)

 Investigations:

1. Biochemical investigations:
  GH levels
 Glucose tolerance test- GH levels are measured during an oral glucose tolerance
test.
 IGF-1 levels: Single best test – Always elevated in acromegaly
 Postprandial plasma glucose- may be elevated.
 Prolactin- Mild to moderate elevation
 Others- Elevated serum phosphorus

2. Radiological investigations:

X-Ray:

 Plain films of skull- Shows sellar enlargement in 90% of cases. Thickening of

the calvarium, enlargement of the frontal & maxillary sinuses, & enlargement of
the jaw.
 Radiographs of the hand- Increased soft tissue bulk, ‘arrowhead’ tufting of the
distal phalanges, increased width of intra-articular cartilages, & cystic changes of
the carpal bones.
 Radiographs of the feet- Increased thickness of the heel pad
 MRI Scan of pituitary- Localizes pituitary adenoma

3. Pituitary function
4. Visual field examination

 Treatment of Acromegaly:

 Aim of therapy: To achieve a mean growth hormone level < 2.5 g/L

1. Surgery: Trans-sphenoidal surgical removal of pituitary adenoma- First line therapy

2. Medical therapy: Drugs used-

a. Somatostatin receptor ligands (SRL)-

90% GH secreting adenomas express somatostatin receptor subtypes (SSTR)
namely SSTR2 & SSTR5.
Mode of Action: Somatostatin analogues (Octreotide, Pasireotide or Lanreotide)
are more effective than dopamine agonists & act on pituitary somatostatin
receptors to produce inhibition of GH & IGF-1.
b. GH Receptor antagonist- Pegvisomant
c. Dopamine Receptor Agonists- Act on D2 receptors.
Bromocriptine or Cabergoline
3. Radiotherapy
4. Others: Treatment of associated conditions such as diabetes, hypertension &
hyperlipidemia.
 Cushing’s Syndrome:
Clinical state of increased free circulating glucocorticoid.
Occurs most often following the therapeutic administration of synthetic steroids or
ACTH.
 Cushing’s Disease: Results from corticosteroid excess due to pituitary dependent
bilateral adrenal hyperplasia.
The pituitary tumors producing Cushing’s disease are usually microadenomas
(<10 mm in size) which usually do not cause symptoms by local mass effect.
It usually develops sporadically but may be a component of multiple endocrine
neoplasia type 1.
 Common Causes of Ectopic ACTH Secretion:
Type of tumor Percentage
Small cell carcinoma of the lung 50%
Endocrine tumors of foregut origin 35%
o Thymic carcinoid
o Pancreatic islet cell tumor
o Medullary carcinoma thyroid
o Bronchial carcinoid
Pheochromocytoma 5%
Ovarian tumors. 2%

 Clinical Features of Cushing’s Syndrome:

 General:
o Weight gain/obesity
o Central obesity
o Buffalo hump
o Moon face
o Hypertension
 Skin:
o Hirsutism
o Plethoric appearance
o Purplish striae over abdomen, buttocks and thighs
 o Bruising
 Musculoskeletal:
o Back pain
o Muscle weakness
 Gonadal dysfunction:
o Menstrual disorders (oligomenorrhoea, amenorrhea, decreased libido and impotence)
 Neuropsychiatric:
o Emotional lability, depression, euphoria, psychosis, irritability
 Metabolic:
o Glucose intolerance
o Diabetes
o Hyperlipidemia
o Polyuria
o Kidney Stones

 Hypokalemia due to the mineralocorticoid activity of cortisol is common in the ectopic

ACTH secretion
 Proximal muscle weakness, sleep apnea, osteoporosis, hypertension are common features
of disease
 Mnemonic for Cushing’s Syndrome:
C Central obesity, Collagen fiber weakness, Comedones (acne)
U Urinary free cortisol increased along with glucose
S Striae, Suppressed immunity
H Hypercortisolism, Hypertension, Hyperglycemia, Hypercholesterolemia
I Iatrogenic due to administration of corticosteroids
N Non-iatrogenic, Neoplasms
G Glucose intolerance, Growth retardation

 Investigations in Cushing’s Syndrome:

 48-hour low-dose dexamethasone test

  24-hour urinary free cortisol measurements- This is simple, but less reliable-
repeatedly normal values (corrected for body mass) render the diagnosis most unlikely,
but some patients with Cushing’s have normal values on some collections.
 Plasma cortisol levels- Measurement at 8 AM & 12 midnight will show the lowest
levels at midnight. Circadian rhythm is lost in Cushing’s Syndrome & the cortisol
levels remain the same throughout the day. A midnight level <1.8g/dl is normal, &
has a high sensitivity for excluding Cushing’s syndrome.
 Overnight dexamethasone suppression test
 Low-dose dexamethasone suppression test
 Late-night salivary cortisol- Maybe used as a screening test for Cushing’s syndrome.
Concentration of cortisol in saliva is highly correlated with free plasma cortisol.
 Tests that establish the cause of Cushing’s Syndrome:
 Plasma ACTH level at 8 AM
 Interpretation of plasma ACTH levels:
Level of plasma ACTH Probable source of ACTH as
Normal values (10-80 ng/L) Pituitary
Intermediate values (80-300 ng/L) Pituitary dependent disease or ectopic ACTH syndrome
Very high levels (>300 ng/L) Ectopic ACTH Syndrome
Low ACTH (<10 ng/L) Adrenal tumors, macronodular adrenal hyperplasia or
exogenous steroid administration

 High-dose dexamethasone suppression test

 Tests in Cushing’s Syndrome:
Test & Protocol Measure Normal test result or Use & explanation
positive suppression
Dexamethasone Overnight
(for Cushing’s)
Take 1 mg on going to bed at Plasma Plasma cortisol <100 Outpatients screening
23:00 h Cortisol at nmol/L test. Some ‘false
9:00 h next positives’
morning
‘Low Dose’
0.5 mg 6-hourly Plasma Plasma cortisol <50 For diagnosis of
8 doses from 9:00 h on day 0 Cortisol at nmol/L on second Cushing’s syndrome
9:00 h on days sample
0 and +2
‘High Dose’ used in
differential diagnosis
2 mg 6-hourly Plasma Plasma cortisol on day Differential diagnosis
8 doses from 9:00 h on day 0 Cortisol at +2 less than 50% of of Cushing’s
9:00 h on days that on day 0 suggests syndrome
0 and +2 pituitary-dependent Pituitary-dependent
disease disease suppresses in
about 90% of cases

 Plasma potassium levels

 ACTH/ Cortisol response to corticotrophin-releasing factor (CRF)
o Increased in pituitary dependent disease
o Unchanged in ectopic ACTH syndrome & tumors of adrenal gland
 Bilateral inferior petrosal sinus sampling for ACTH before & after CRF stimulation
 Other investigations:
 Biochemical investigations: Blood glucose, cholesterol & LDL may be raised.
 Radiological investigations:
o Plain radiograph
o CT scan
o CT/MRI head and MRI abdomen

 Management:
1. Adrenal tumors:
 Surgical resection-
o Adrenal adenomas: Surgical removal
o Adrenal carcinomas: Surgical resection
 Medical adrenalectomy- Medications that inhibit steroidogenesis include
ketoconazole, metyrapone & octreotide.
2. Cushing’s disease:
  Treatment of choice: Trans-sphenoidal removal of the tumor
 Radiotherapy & radiosurgery for recurrent or residual ACTH-secreting tumors
 Medical therapy to reduce ACTH (e.g. bromocriptine)
 Bilateral adrenalectomy: Done if the diagnosis is uncertain
3. Ectopic ACTH Syndrome:
 Surgical removal of benign tumors
 Radiotherapy and chemotherapy

 Aphasias:
 Aphasia is loss or defective language content of speech resulting from damage to the
speech centers within the dominant hemisphere.
 A language disturbance occurring after a right hemisphere lesion in a right hander is
known as crossed aphasia.
 It includes defect in or loss of the power of expression by speech, writing or gestures or
a defect in or loss of the ability to comprehend spoken or written language or to interpret
gestures.
 Aphasias may be categorized according to whether the speech output is fluent or
nonfluent:
1. Fluent aphasia (Receptive aphasia) are impairments mostly due to input or reception
of language, with difficulties either in auditory verbal comprehension or in the
repetition of words, phrases or sentences spoken by others. Example: Wernicke’s
aphasia
2. Non fluent aphasia (expressive aphasias) are difficulties in articulating, with relatively
good auditory, verbal comprehension. Example: Broca’s aphasia

 Types of Aphasias:
Type of Site of lesion Compreh Fluency Repetition Reading Writing Naming
Aphasia ension
Wernicke’s/s Infarction of Absent Preserve Absent - - -
ensory/ inferior division d
receptive/pos of middle
terior cerebral artery
Broca’s/ Infarction of Preserve Absent Absent - - -
motor/ superior frontal d
expressive/ branch of
anterior middle cerebral
artery
Global Dominant Absent Absent Absent - - -
frontal, parietal
and superior
temporal lobe
Conduction/ Arcuate fascile Preserve Preserve Absent - - -
arcuate d d
Transcortical Posterior Absent Preserve Preserved - - -
sensory watershed zone d
Transcortical Anterior Preserve Absent Preserved - - -
motor watershed zone d
Alexia Occipitotempora Preserve Preserve Preserved Lost Preserv -
without l region d d ed
agraphia
Alexia with Left angular Preserve Preserve Preserved Lost Lost -
agraphia gyrus d d
Nominal/ Temporoparietal Preserve Preserve Preserved Preserv Preserv Absent
anomic/ d d ed ed
amnesic

 Migraine:

 Neurovascular disease caused by neurogenic inflammation & characterized by

severe, recurring headaches.
 Second most common cause of headache.
 Usually characterized by an episodic severe pain on one side of the head
(headache) & usually associated with certain features such as sensitivity to light,
sound or movement; nausea & vomiting often accompany the headache.
 Classification:

 Migraine without aura or common migraine: Does not give any warning signs
 Migraine with aura or classical migraine: Gives some warning signs called ‘aura’
before the actual headache begins.
o Most common aura is visual and may include both positive and negative
(visual field defects) features.

 Pathogenesis:
 Cause of migraine is not known.
 Genetic factors: Role in causing the neuronal hyperexcitability. Migraine is usually
polygenic. Rarely, familial migraine is associated with mutations in the 1 subunit of
the P/Q type voltage gated calcium channel or neuronal sodium channel (SCN1A) &
a dominant loss of function mutation in a potassium channel gene (TRESK).
 Hormonal influences: Female preponderance and the frequency of migraine attacks
at certain points in the menstrual cycle due to hormonal fluctuations. Estrogen-
containing oral contraception can exacerbate migraine in few patients.
 Right to left cardiac shunt: Migraine with aura has been associated with patent
foramen ovale (PFO), atrial septal defect (ASD) and pulmonary arteriovenous
malformations in hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu
Syndrome).

 Several theories have been proposed for the pathogenesis of migraine:

 Vascular theory: Constriction of intracerebral blood vessel produces aura.

Vasodilatation of intracranial/extracranial blood vessel produces headache
phase.
 Serotonin theory: Deceased serotonin levels linked with migraine and specific
serotonin receptors found in the blood vessels of brain.
 Neurogenic theory: The aura is thought to be due to spreading of cortical
depression wave of neuronal depolarization followed by depressed activity
spreading slowly anteriorly across the cerebral cortex from the occipital region.
Dysfunction of activation of cells in the trigeminal nucleus releases vasoactive
 neuropeptides by activated trigeminovascular neurons. They produce painful
meningeal inflammation and vasodilation.
 Dopamine: Plays a role and most migraine symptoms can be induced by
dopaminergic stimulation.

 Precipitation factors: Anything can initiate or precipitate or amplify an attack.

Common triggers are excess stress, glare, exposure to bright light, loud noises/
sounds, smoke or strong scents, menstruation, lack of sleep, cheese, caffeine, alcohol,
chocolate, citrus fruit, food additives, vasodilators, hunger, physical exertion, stormy
weather or barometric pressure changes and contraceptive pills.

 Clinical features:

Headache is usually hemicranial, throbbing & associated with nausea and vomiting.
 Migraine without aura (previously called ‘common’ migraine):
o About 70-80% of patients have characteristic headache but without aura.
o Typically, attacks are episodic and start at puberty and prevalence increases in 4 th
decade.
o The scalp may be tender in touch during episodes (allodynia is production of pain
from normally non-painful stimuli) and the patient prefer to be still in a dark and
quiet environment.
Nausea Vomiting
Photophobia, prostration Visual disturbances
Lightheadedness Paresthesias
Scalp tenderness/ cutaneous allodynia Vertigo

 Migraine with aura (previously called ‘classical’ migraine):

o About 20-30% of patients experience malaise, irritability, behavioural change or
focal neurological symptoms for some hours or days immediately preceding the
headache phase.
o Types of Aura:
1. Visual Aura: Most common type characterized by positive visual symptoms
such as shimmering, teichopsia (silvery zigzag lines also called fortification
 spectra) flashing lights or fragmentation of the image (like looking through a
pane of broken glass) or scintillating spots across the visual fields for up to 40
minutes.
2. Sensory Aura: It consists of positive sensory symptoms such as tingling
followed by numbness, spreading over 20-30 minutes, from one part of the
body to another.
3. Language Aura: Dominant hemisphere involvement may cause transient
speech disturbance.
4. Motor aura-transient weakness.

 Simplified Diagnostic Criteria for Migraine:

Repeated attacks of headache lasting 4-72 hours (untreated) with:
Atleast 2 of the following features: Plus atleast 1 of the following features:
 Unilateral pain  Nausea/ Vomiting
 Throbbing pain  Photophobia and phonophobia
 Motion sensitivity (headache  Normal physical examination, no
aggravated with head movement or other reasonable cause for the
physical activity) headache
 Moderate or severe intensity

 Red flags of headache:

 ‘Worst’ headache ever

 First severe headache
 Subacute worsening over days or weeks
 Altered level of sensorium/ consciousness
 Abnormal neurological examination
 Fever or unexplained systemic signs
 Significant weight loss
 Vomiting that precedes headache
 Pain induced by bending, lifting, cough, Worsens with Valsalva maneuvers
 Pain which disturbs sleep or presents immediately upon awakening
 Known systemic illness, history of trauma, cancer or HIV
  New onset headache in a patient >50 years of age
 Focal neurologic deficits, jaw claudication
 Morning headache associated with nausea and vomiting
 Pain associated with local tenderness (e.g. region of temporal artery)

 Management:

 Nonpharmacological treatment (General measures):

 Explanation that migraine has no grave prognosis
 Identification of triggers and avoidance of identified triggers or exacerbating factors to
prevent attacks. Women with aura should avoid estrogen treatment (oral contraception
or hormone replacement). Lifestyle modifications wherever possible.
 Other measures: Medication, relax techniques, psychotherapy

 Pharmacological treatment:
 Abortive treatment – treatment of acute attack
 Preventive treatment: Drug prophylaxis

 Treatment of an acute attack:

 Analgesics: Simple analgesia such as aspirin, paracetamol or nonsteroidal anti-
inflammatory agents
 Nausea may be treated by antiemetic (metoclopramide or domperidone).
 Severe attacks: If there is previously no relief with an NSAID, use ‘triptans’.
 Triptans: E.g. Sumatriptan, Almotriptan, Eletriptan, Frovatriptan, Naratriptan,
Rizatriptan and Zolmitriptan.
 CGRP (calcitonin gene-related peptide) antagonists (e.g. telcagepant) are very
effective for acute treatment of migraine.
 Lasmiditan, a selective serotonin 1F receptor agonist has been tried.
 Single pulse transcranial magnetic stimulation (TMS) has been shown good
benefits.

 Drug Prophylaxis:
Various drugs can be used and the most frequently used are:
 Anticonvulsants: Valproate or Topiramate
 -adrenoceptor antagonists ( -blockers), e.g. Propanolol
 Tricyclic antidepressants, e.g. amitriptyline
 Methysergide
 Botulinum toxin
 Vasoactive drugs and calcium channel blockers: Flunarizine, Verapamil
 Butterbur, Coenzyme Q10

 Treatment of Migraine:

Acute Attack Prophylaxis/ Preventive

Nonspecific treatment Specific treatment * Anticonvulsants (antiepileptic drugs)

* Tricyclic antidepressants
NSAID Antiemetics Triptans Dihydroergotamine * Calcium channel blockers
* -adrenoceptor antagonists (-blockers)

 CSF Findings in Meningitis:

Normal Acute Pyogenic Acute viral Tuberculous

(aseptic)
Physical Clear and Turbid and Clear Clear and colorless,
examination colorless forms coagulum forms cobweb on
standing due to
coagulation of
fibrinogen
CSF Pressure 60-150 mm of Raised above Raised Raised above 300
H2O 180 mm of H2O above 250 mm of H2O
mm of H2O
Total Protein 20-40 mg/100 > 50-200 > 40 50-150 mg/100 ml
ml (<0.45 g/L) mg/100 ml mg/100 ml
Glucose 45-80 mg/100 0-20 mg/100 ml Normal Decreased: May be
ml (>50-60% of (usually <=40 <45mg/ 100 ml
blood level) mg/dl)
Chlorides 720-750 600-700 ng/100 Normal 450-600 mg/ 100 ml
mg/100 ml ml
Cells
Polymorphs Usually absent 1000-5000/L Absent 0-5 cells/L
Lymphocytes 0-5 cells/L 5-50 cells/L 10-2000 50-5000 cells/L
 cells/L
Gram stain/ ZN - Bacteria+ AFB+ (Ziehl-
stain Neelson/auramine
stain) on
tuberculosis culture
positive

 Gullian Barre Syndrome:

 Heterogenous group of immune-mediated conditions.

 GBS is the most common acute, severe fulminant polyradiculopathy/
polyneuropathy.
 Usually demyelinating or rarely axonal

 Variants of GB Syndrome:

 Acute Motor and sensory axonal neuropathy (AMSAN)

 Acute Motor axonal neuropathy (AMAN)
 Miller Fischer Syndrome (MFS)
 Pure motor variants
 Pure sensory variants
 Pure dysautonomia variant
 Pharyngeal-cervical-brachial variant
 Paraparetic variant (Ropper variant)

 Etiology: Infections preceding GBS may be due to Campylobacter jejuni,

cytomegalovirus, Epstein-Barr virus, herpes virus, CMV and Mycoplasma
pneumoniae.

 Immunopathogenesis:

 Gullian Barre syndrome is an acute onset immune mediated demyelinating

neuropathy. Autoimmune basis for AIDP (GBS) and other subtypes.
 Antiganglioside antibodies mostly to GM1 common in GBS
 Anti-GQ1b IgG antibodies seen in MFS

 Clinical Features:

 Hallmark is an acute/ rapid onset of paralysis evolving over days or weeks with
loss of deep tendon reflexes/ jerk (areflexia)
 Motor paralysis predominant. Weakness beginning in the distal limbs that
rapidly ascends to affect proximal muscle function (‘ascending paralysis’)
 Sensory involvement is minimal and may precede muscle weakness.
 Facial and respiratory muscle weakness develops in 20-30% of cases requiring
ventilatory support.
 No fever or constitutional symptoms at the onset of weakness
 Bladder dysfunction
 Clinical worsening in 4 weeks
  Autonomic disturbances common like fluctuation of BP, postural hypotension,
cardiac dysrhythmias
 Pain- common symptom acute/deep aching pain in weak muscles. It is self-
limited.
 Physical examination shows diffuse weakness with loss of reflexes.
 Miller- Fischer Syndrome: It presents with ophthalmoplegia, ataxia and
areflexia.

 Investigations/ Diagnosis:

 CSF Findings: Develop after 1 week of illness.

o Raised protein, normal sugar, little or no pleocytosis
This is called albumin-cytological dissociation.
 Electrodiagnostic study: Nerve conduction studies:
o In mild/early stage: Normal
o In demyelination: Prolonged distal latencies, slow conduction
 Antibodies:
o Antibodies against GQ1b, a ganglioside component of nerve
o Miller Fischer Syndrome: Antibodies against GQ1b

 Treatment:

 Intravenous immunoglobin: IVIg administration has fewer side effects

 Plasma exchange: Glucocorticoid no role
 Supportive measure: Deep vein thrombosis (DVT) prophylaxis, tracheostomy, chest
physiotherapy, skincare, bed sore, joint physiotherapy, daily reassurance

 Indications for Plasma Exchange:

o Glomerulonephritis- anti- GBM disease

o Gullian Barre Syndrome
o Myasthenia Gravis
o Autoimmune encephalitis
o Prerenal transplant
o Systemic vasculitis not responding adequately to immunosuppressive therapy
o Thrombotic thrombocytopenic purpura

 Parkinson’s Disease:

Parkinsonism is a syndrome consisting of a variable combination of tremor, rigidity,

bradykinesia, and a characteristic disturbance of gait and posture.

 Classification of Parkinsonian Disorders:

Primary Secondary Parkinsonism Plus

Syndrome

Parkinson’s Disease (PD) Toxin, e.g. MPTP

 Viral, e.g. Encephalitis lethargica
Sporadic Familial Metabolic, e.g. Wilson’s disease
Head injury, e.g. Punch-Drunk Syndrome
Infectious, e.g. Postencephalitic, HIV
Drugs, e.g. Dopamine receptor blocking drugs
Vascular, e.g. multi-infarct
Trauma, e.g. Pugilistic encephalopathy

 Idiopathic Parkinson’s Disease (Paralysis Agitans):

 It is a chronic progressive disorder in which idiopathic parkinsonism occurs without

evidence of more widespread neurologic involvement.
 Average age of onset- 60 years
 Prevalence is higher in men than women.

 Etiology:
Cause of idiopathic Parkinson’s disease (PD) is not known.

 Pathological Features:

 Hallmark of PD: Degeneration and depletion of the pigmented dopaminergic neurons

in the substantia nigra pars compacta (SNc), reduced striatal dopamine, and the
presence of -synuclein and intracytoplasmic proteinaceous eosinophilic inclusions
in nigral cells known as Lewy Bodies.
 The loss of dopaminergic neurotransmission in the nerve cells (>80% ) in the
substantia nigra and other nuclei in the midbrain responsible for the symptoms of
Parkinson’s disease.
 Clinical manifestations:

A. Motor symptoms: Always asymmetrical in onset and become bilateral within a year.
 Tremor: It is an early and presenting symptom in 70% of patients.
Frequency is 4-6 Hz tremor and is typically most prominent at rest and worsen with
emotional stress.
Often described as pill rolling of finger and wrist, because the patient appears to be
rolling something between thumb and forefinger. It often begins with rhythmic
flexion-extension of the fingers, hand, or foot or with rhythmic pronation- supination
of the forearm.
 Rigidity: It is a sign rather than a symptom. Increased resistance to passive
movement is characteristic.
Stiffness on passive limb movement is described as ‘lead pipe’ rigidity because the
increase in muscle tone is present throughout the range of movement.
When tremor is superimposed on the rigidity, a ratchet like jerkiness is felt, described
as ‘cogwheel’ rigidity.
 Akinesia or bradykinesia: Poverty/ slowing of movement are the hallmark of PD.
Slowness/ difficulty of initiating voluntary movement and an associated reduction in
automatic movements, such as swinging of the arms when walking.
There is fixity of facial expression (facial immobility -mask like face)
Repetitive tapping (at about 2Hz) over the glabella (glabellar tap) produces a
sustained blink response (Myerson’s sign).
The combination of tremor, rigidity and bradykinesia results in small, tremulous and
often illegible/ difficult handwriting(micrographia).
 Postural changes: A stooped posture is characteristic
 Gait changes: Slow shuffling, freezing and recued arm swing, small stride length,
slow turns, festinating gait (tendency to advance rapid short steps) and catching centre
of gravity.
 Speech and swallowing: Speech becomes softer (soft voice-hypoplasia), quiet,
indistinct, flat/ monotonous and stuttering, increased salivation/ drooling, and
dysphagia which may lead to aspiration pneumonia as a terminal event.
 Cognitive and psychiatric changes: Cognitive impairment

 Nonmotor symptoms of Parkinson’s Disease:

Autonomic Dysfunction Neuropsychiatric Sensory problems
Orthostatic hypotension Anxiety Reduces sense of smell
(hyposmia)
Urinary incontinence Depression Pain
Constipation Apathy
Sexual problems Psychosis
Dementia
Sleep disorders Rheumatological Other
Restless legs Frozen shoulder Seborrhoea
Insomnia Periarthritis
Daytime somnolence Swan neck deformity

 Investigations/ Diagnosis:
 Diagnosis is made on clinical grounds
 Structural imaging (CT or MRI) is usually normal
  Functional dopaminergic imaging: By single photon emission computed tomography
(SPECT) or positron emission tomography (PET) is abnormal and shows reduced
uptake of striatal dopaminergic markers.
 Dopamine transported (DaT) imaging

 Parkinson plus syndromes and its features:

Syndrome Features:
Progressive supranuclear palsy (PSP, Slow ocular saccades, eyelid apraxia and
Steele-Richardson-Ofszewski Syndrome) restricted eye movements with particular
impairment of downward gaze & reptilian
stare. Frequently, experience
hyperextension of the neck with early gait
disturbance and falls. MRI may reveal a
characteristic atrophy of the midbrain and
relative preservation of the pons (the

G
hummingbird sign’ on mid-sagittal
images)
Multiple- System Atrophy (MSA) Parkinsonism in conjunction with
Parkinsonian (MSA-P) or striatonigral cerebellar signs and/or early and
degeneration prominent autonomic dysfunction, usually
Cerebellar (MSA-C) or orthostatic hypotension.
olivopontocerebellar atrophy) Cerebellar and brainstem atrophy (the
Autonomic (MSA-A) form or Shy-Drager pontine ‘hot cross buns’ sign in MSA-C)
Syndrome
Corticobasal ganglionic degeneration Asymmetric dystonic contractions and
(Rebeitz- Kolodny- Richardson Syndrome) clumsiness of one hand couples with
cortical sensory disturbances manifest as
apraxia, agnosia, focal myoclonus, or
alien limb phenomenon
Dementia with lewy bodies Early onset dementia, visual
hallucinations
Parkinsonism- dementia complex of Guam Motor neuron disease plus Parkinson’s
Guadeloupean Parkinsonism Levodopa-unresponsive parkinsonism,
 postural instability with early falls, and
pseudobulbar palsy

 Treatment:
 Anticholinergic drugs: Trihexyphenidyl, benztropine and orphenadrine.
 Levodopa: It is the metabolic precursor of dopamine. It is the single most effective
drug available for the treatment. It particularly helpful in relieving bradykinesia.
It is metabolized by MAO and COMT.
On and off effect: Important late complication of levodopa therapy.
 MAO-B Inhibitors: Monoamine oxidase type B facilitates breakdown of excess
dopamine in the synapse.
The addition of selegiline, a monoamine oxidase B inhibitor, reduces the metabolic
breakdown of dopamine and may slow down the degeneration in the substantia nigra.
 Dopamine receptor agonists: They are classified as ergot derived (bromocriptine,
pergolide and cabergoline) or non-ergot derived (pramipexole, ropinirole, rotigotine
and apomorphine).

 COMT (Catechol-O-Methyltransferase) Inhibitors:

COMT produces peripheral breakdown of levodopa (e.g. entacapone and tolcapone)
Entacapone prolongs the duration of levodopa by decreasing its peripheral
metabolism.

 Dopamine Facilitator:
o Amantadine: It is an antiviral agent that potentiates dopaminergic function by
influencing the synthesis, release, reuptake of dopamine.

 Peripheral dopamine decarboxylase inhibitors (PDI):

It does not penetrate the BBB (blood brain barrier), reduce the peripheral metabolism
of levodopa. E.g. Carbidopa, Benseraside

 Neuroprotective agents that alter pathogenesis:

MAO Inhibitors: Selegiline and Rasagiline

 Surgical treatment:

 Indications: Most common indications for surgery in PD are intractable tremor and
drug-induced motor fluctuations or dyskinesias.
 Stereotactic surgery (ventrolateral thalamotomy)
 Pallidotomy
 Deep brain stimulation (DBS)- Best site is subthalamic nucleus
  Characteristics of Extrapyramidal Lesion:

Sign Site of lesion

Resting tremor Substantia nigra, red nucleus
Muscular rigidity Substantia nigra, putamen
Hypokinesia Substantia nigra, globus pallidum
Chorea Caudate nucleus
Hemiballismus Subthalamic nucleus
Dystonia, athetosis Putamen

 Alzheimer’s Disease:

 Most common cause of dementia in the world.

 Most common cause of dementia above the age of age of 40.

 Etiology: Mutations: Point mutations in amyloid precursor protein (APP) can cause
AD.
Mutations in the gene presenilin-1 (PS-1) and preselinin-2 (PS-2).
The inheritance of one of the alleles of apolipoprotein E4 (apo E4).

 Clinical Features:

 Memory impairment/ loss: Early recent (short-term) memory loss is key feature of
AD.
 Language problem: Next common symptom
 Apraxia: Impaired ability (inability) to carry out (perform) skilled, complex,
organized motor activities.
 Agnosia: Failure to recognize objects (e.g. clothing, places or people)
 Frontal execution function: Impairment of organizing, planning and sequencing.
 Parietal presentation: Visuospatial difficulties and difficulty with orientation in
space.
 Myoclonic jerks
 Generalized seizures

 Investigations:

 Neuroimaging studies (CT and MRI) are not specific for AD.
As AD progresses, diffuse cortical atrophy becomes apparent, and detailed MRI
scans show atrophy of the hippocampus.
 CSF Markers: 1. Raised tau proteins 2. Low B42 amyloid 3. Elevated ceramides
level

 Diagnostic Criteria for Alzheimer’s Disease:

 Memory impairment
 One or more of the following: - Apraxia
- Aphasia
- Agnosia
- Disturbance in executive functioning
 Treatment: There is no specific treatment.

 Focus is on long term amelioration of associated behavioural and neurologic problems

o Drugs:

Drug and dosage Adverse drug reactions

Tacrine: 80-160 mg/day Liver toxicity, nausea, vomiting, diarrhea
Donepezil: 5 and 10 mg/day Nausea, vomiting, diarrhea, muscle cramps
Rivastigmine: 6 -12 mg/day Nausea, vomiting, diarrhea, headache, dizziness
Galantamine: 20-50 mg/day Nausea, vomiting, agitation, sleep disturbances

 Memantine appears to act by blocking overexcited N-methyl-D-Aspartate NMDA

channels.
 Statins may have protective effect on dementia especially vascular. Antioxidants
(Vitamin E, Selegine), Estrogen replacement, Gingko biloba have been tried.
 Mild to moderate depression is common in the early stages of AD and responds to
antidepressants. Selective serotonin reuptake inhibitors SSRIs are commonly used due
to their low anticholinergic side effects.
o Newer developmental agents:
 Immunization against -amyloid.
 Huprine X-acetylcholinesterase inhibitor
 Xanomeline patch-m1/m4 muscarinic receptor agonist
 AIT-082 (purine hypoxanthine derivative)- increases neurotransmission
 COX-2 inhibitors- neuroinflammation therapy
 Protease inhibitors- target gamma- secretases to prevent amyloid formation.

 Systemic Sclerosis (Scleroderma):

Systemic Sclerosis (SSc) is a chronic multisystem disease of connective tissue affecting the
skin, musculoskeletal system, internal organs and vasculature.
Scleroderma literally means ‘hard skin’ and the hallmark of SSc is thickening and hardening
of the skin (scleroderma) due to fibrosis.

 Classification:

 Diffuse Cutaneous Systemic Sclerosis (DCSS- 30% of cases)- It is associated with

progressive skin thickening, starting in the fingers and ascending from distal to proximal
extremities, the face and trunk.

 Limited Cutaneous Systemic Sclerosis (LSCC- 70% of cases)- These patients have
long standing Raynaud’s phenomenon before other manifestations. Skin involvement
progresses slowly and remains limited to the fingers (sclerodactyly), distal extremities
and face, without involvement of trunk.

Few of the patients have prominent Calcinosis cutis, Raynaud’s phenomenon,

Esophageal dysmotility, Sclerodactyly (scleroderma of the fingers) and Telangiectasia,
which is termed CREST Syndrome. It usually shows slow progression.
 Age and gender: 30-50 years of age with female to male ratio of 3:1.

 Etiology: There are associations with alleles at HLA locus have been found. There is
immunological dysfunction of T-lymphocytes, especially Th1 and Th17 subtype.

 Skin Manifestations:

o Limited disease or CREST syndrome

o Diffuse disease: Skin involvement proximal to the knee and elbow and on the trunk.

 Changes in skin:

o Early stage: shows non-pitting edema of fingers and flexor tendon sheaths
o Later stage: Skin becomes shiny, firm, thickened and distal skin creases disappear.
o Hyperpigmentation: Salt and pepper appearance most prominently on the upper back
and chest.
o Changes in facial skin: Produces a beak-like nose, ‘mask-like’ face and decreased oral
aperture (microstomia)
o Other manifestations: Flexion contractures, ulcers over fingerprints and bony
prominence, telangiectasia.

 Musculoskeletal Manifestations:
o Range from mild arthralgias to frank nonerosive arthritis with synovitis resembling
rheumatoid arthritis.
o Generalized arthralgia, morning stiffness and flexor tenosynovitis are common
o Muscle weakness and wasting due to disuse atrophy, myopathy and myositis.

 Vascular Manifestations:

o Raynaud’s phenomenon: Episodic reversible vasoconstriction of the vessels of the

digits
o A diffuse vasculopathy of peripheral arteries
o Vascular disease is fundamental to organ damage and subsequent malfunction of the
heart

 Gastrointestinal Manifestations:

o Esophageal involvement: Esophagitis, dysphagia and odynophagia, strictures and

dilatation and atony of lower esophagus
o Stomach involvement: Watermelon stomach
o Small and large bowel involvement: Pseudo-obstruction

 Pulmonary Manifestations:

o Inflammatory alveolitis
o Pulmonary hypertension

 Other Manifestations:
 o Renal involvement: Acute hypertensive renal crisis & renal failure – most common
cause of death
o Cardiac involvement: Myocardial fibrosis and cardiomyopathy

 Diagnosis:

o ESR: Elevated
o IgG levels: Raised
o Anemia: May be due to 1. Chronic disease 2. Iron deficiency 3. Folate and B 12
deficiency 4. Microangiopathic Hemolytic Anemia
o Urea and creatinine
o Urine microscopy
o Autoantibodies associated with scleroderma
o Rheumatoid factor
o Nailfold capillary changes

o Imaging:

o Chest X-Ray
o X-Ray of hands
o Barium Swallow
o High-Resolution CT

 Criteria for diagnosis of scleroderma:

o Thickened (sclerodermatous) skin changes proximal to the metacarpophalangeal
joints
OR
o At least two of the following:
- Sclerodactyly
- Digital pitting (residual loss of tissue on the finger pads due to ischemia)
- Bibasilar pulmonary fibrosis

 Autoantibodies associated with scleroderma:

 Antinuclear antibody
 Anti-Scl-70 (anti-topoisomerase 1)
 Anti-centromere
 Anti-RNA polymerases
 Anti-B23
 Anti-Pm-Scl
 Anti-U3-RNP (anti-fibrillarin)
 Anti-U1-RNP
 Anti-Th/To

 Treatment:
There is no cure and no treatment can halt or reverse the fibrotic changes produced in
systemic sclerosis. Treatment should be organ-based to ameliorate the effects of the disease
on target organs.
  Control of Raynaud’s syndrome and digital ulcers:
o Raynaud’s phenomenon: Avoid triggering factors: Use hand warmers, and oral
vasodilators (calcium-channel blockers)
o Digital ulcers: Endothelin-1 antagonist Bosentan promotes healing of digital ulcers
 Surgical management: Lumbar sympathectomy
 Hypertension: Treated aggressively with ACE inhibitors
 Esophageal Reflux: Symptomatic malabsorption requires nutritional supplements.
 Joint involvement: Treated with analgesics and/or NSAID.
 Pulmonary hypertension: Treated with oral vasodilators, oxygen and warfarin.
 D-Penicillamine

 PSVT: Paroxysmal Supra-Ventricular Tachycardia:

 Stable Vital Signs: Carotid Massage  Adenosine (6,12, 12 mg) IVP  Verapamil
(2.5mg  5mg) IV slow
 Unstable Vital Signs: Synchronized Cardioversion 50 Joules
 Rate: Rate changes abruptly and unexpectedly. Rate change occurs in a single beat.
Rate may increase up to 100-250/min, but most often between 140-250/min
 P-waves: may not be discernible during PSVT phase
 Rhythm IV – Usually not possible to measure
 P-R: Normal if P-waves are discernible
 QRS: Usually narrow

 Wolff-Parkinson-White Syndrome:

WPW syndrome is a congenital pre-excitation syndrome characterized by an accessory

pathway that connects the atria and ventricles.

 Symptoms:
o Rapid heart rate
o Chest pain
o Dizziness

 How to identify on ECG: Triad

o Short PR interval (<120 msec)
o Prolonged QRS (>120 msec)
o Delta wave: Slurred upstroke of QRS

Acute Treatment of Non-medical therapy Valsalva Maneuver

Symptomatic WPW
Carotid sinus massage
Pharmacological therapy Adenosine
(AV Nodal-blocking agents)
Verapamil
Procainamide or -blockers
Treatment of recurrent Procedural therapy Catheter ablation (preferred)
arrhythmias in WPW

 Management of VT-
  Stable
o Amiodarone (Structural heart disease):
-150 mg IV bolus x 10 min followed by
- 1 mg/min x 6 hr & 0.5 mg/min x 18 hrs
o Procainamide (DOC if no heart disease)
-20 to 50 mg/min (Max: 17 mg/kg)
o Lignocaine (Post MI, no structural heart disease)
o Sotalol

 Hemodynamically unstable
o Synchronized DC
o Cardioversion 100-360 J

 Note: Unsyncronised Cardioversion: Pulseless VT, Polymorphic VT, Ventricular

fibrillation
 Immediate defibrillation

2g IV MgSO4 over 10 mins

Rhythm stabilization

Congenital. Acquired

-blockers Treatment of Cause

 Cardioversion Vs Defibrillation:

 Cardioversion: Current discharged at the same time as patient’s QRS

 Defibrillation: Current discharged through defibrillator machine
 Risk of V.Fib if current discharged at vulnerable period of T-wave
 Vulnerable period: 20-30 ms on T-wave.

 Procedure:
o Synchronized: Sync cardioverter/defibrillator with patient’s rhythm
o Unsynchronized: No need to connect electrode to patient

 Paddles:
1. Right side of upper sternum below clavicle
2. Apex of heart (Left of nipple)

 Energy: Start with 50 J

o A.Fib : 100-200 J
o A.Flutter: 50 J
o Polymorphic VT: 200 J
o Monomorphic VT: 100 J

 Bartter’s Syndrome:

Features: Bartter Syndrome Gitelman’s Syndrome

 (Mimics Loop Diuretics) (Mimics Thiazide Diuretics)
Inheritance Autosomal Recessive Disorder Autosomal Recessive Disorder
Pathophysiology Genetic defect in the thick Genetic defect in the distal
ascending limb of the Loop of tubule
Henle Defects in Na-Cl cotransporter
Defects in Na-K-2Cl in the distal tubule
cotransporter, K or Cl channels
result in lack of concentrating
ability
Age of presentation Early in life Late childhood or early
adulthood
Clinical Presentation No Hypertension No Hypertension (Can see
Polyuria and polydipsia lower average blood pressure
common due to salt wasting)
Neuromuscular symptoms are Polyuria and nocturia in 50-
uncommon or mild 80%
*Often presents with Often presents with
sensineural deafness, triangular neuromuscular symptoms such
facies with drooping mouth, as muscle cramping and
large eyes and pinnae, and renal spasms, significant fatigue.
failure
Lab Data Chloride resistant metabolic Chloride resistant metabolic
alkalosis alkalosis
Hypokalemia Hypokalemia
Normal serum magnesium (may Hypomagnesemia
be low)
Increased urinary calcium Decreased urinary calcium
excretion excretion
(Hypercalciuric so at risk for (Hypocalciuric so no increased
kidney stones or risk of kidney stones or
nephrocalcinosis) nephrocalcinosis)
Renal PGE2 Production Increased Normal

 Note that serum calcium levels tends to be normal in patients with Gitelman’s
Syndrome due to lower PTH levels, increased plasma renin and aldosterone/K+ levels.

Presentation Diagnosis
Hypokalemic Metabolic alkalosis with Liddle’s Syndrome
Hypertension
Hypokalemic Metabolic Alkalosis without Bartter’s Syndrome (Increased Urinary Ca+
Hypertension Excretion)
Gitelman’s Syndrome (Decreased Urinary
Ca+ Excretion

Features Gitelman’s Syndrome Bartter Syndrome Liddle’s Syndrome

Inheritance Autosomal recessive Autosomal recessive Autosomal dominant
Mutation SLC12A3 (NCCT) and SLC12A1, CLCN1CB SCNN1B or
CLCNKB and KCNJ1 SCNN1G
Age at Late Neonatal Childhood/adulthood
presentation childhood/adulthood stage/infancy/adulthood
Symptoms Non-specific Polyuria/ polydipsia/ Non-
/musculoskeletal/ failure to specific/weakness/
chondrocalcinosis thrive/seizure/tetany fatigue/ symptoms of
hypertension
Biochemical Hyperchloremic Hyperchloremic Hypernatremic,
hypokalemic alkalosis hypokalemic alkalosis hypokalemic
Hypomagnesemia Increased renin: alkalosis
Increased renin: aldosterone ratio Low renin:
aldosterone ratio aldosterone ratio
Urine analysis Low calcium levels High calcium/PGE2 Normal calcium
levels levels
Nephrocalcinosis No Yes No
Treatment K/Mg2+ replacement K replacement and Low salt diet
Potassium-sparing potassium-sparing Amiloride
diuretics diuretics
PG synthetase inhibitor

 Acid Base Physiology:

Metabolic acid-base disorders cause HCO3- alterations. Respiratory acid-base disorders

cause PCO2 alterations.

pH PCO2 HCO3- Compensatory

Response
Metabolic Decreased Decreased Decreased Hyperventillation
Acidosis (immediate)
Metabolic Increased Increased Increased Hypoventillation
Alkalosis (immediate)
Respiratory Decreased Increased Increased Increased renal
Acidosis (HCO3-)
reabsorption
(delayed)
Respiratory Increased Decreased Decreased Decreased renal
Alkalosis (HCO3-)
reabsorption
(delayed)

Henderson- Hasselbach Equation: pH= 6.1 + log [HCO3-]

0.03 PCO2

Predicted respiratory compensation for a simple metabolic acidosis can be calculated using
the Winters formula. If measured PCO2 > Predicted PCO2  Concomitant respiratory
acidosis; if measured PCO2 < Predicted PCO2  Concomitant respiratory alkalosis

PCO2= 1.5 [HCO3-] + 8 +/- 2