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Marrow

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World of Revision

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Medicine
Instructions

• Notes are to be used in conjunction with Marrow videos.

Please note:
• The information in this book has been printed based on the transcript of the Marrow videos. This
book has to be used in conjunction with the Marrow videos and not as a standalone material.

• The information contained in this book is for educational purposes only. The content provided is
not intended to substitute for professional medical advice, diagnosis or treatment.

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• This book cannot be sold separately. It has been made available to only select eligible users who

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have an active subscription to Marrow videos.
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• The text, images, slides, and other materials used in this book have been contributed by the
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faculty, who are subject matter experts. We have merely reproduced them as video transcripts in
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this book.
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• The notes have been consciously designed in a way that is concise and revisable. To ensure this,
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we have intentionally added only the most relevant modules and images that are needed for you.
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• The notes contain blank spaces primarily for labelling diagrams, completing cycles and more to
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promote active engagement and reinforce learning.

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• Reasonable care has been taken to ensure the accuracy of the information provided in this book.
Neither the faculty nor Marrow takes any responsibility for any liability or damages resulting from
applying the information provided in this book.

All Rights Reserved

No part of this publication shall be reproduced, copied, transmitted, adapted, modified or stored in any form or
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©Marrow
Contents

Medicine
Basics of Pituitary Gland 1
Anatomy  Pituitary cells and hormones  Hypothalamo-hypophyseal system 
Pituitary imaging and relations

Anterior Pituitary Disorders : Part 1 6

Prolactin  Pituitary adenoma  Prolactinoma  Growth hormone  Acromegaly

Anterior Pituitary Disorders : Part 2 16

Non-functional tumors  Acquired hypopituitarism  Pituitary apoplexy  Sheehan

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syndrome vs. Lymphocytic hypophysitis

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Posterior Pituitary Disorders 20

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Anti-diuretic hormone (ADH)/AVP  AVP deficiency/central DI  Polyuria  AVP
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resistance/nephrogenic DI  Management of DI  Antidiuretic hormone
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(ADH)  Hyponatremia  SIADH
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Adrenal Cortex 29
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Anatomy of cortex  Synthesis of hormones  Primary hyperaldosteronism

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(PHA)  Adrenal insufficiency (AI)  Cushing’s syndrome

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Adrenal Medulla 37
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Physiology of adrenal medulla  Pheochromocytoma  Multiple endocrine neoplasia (MEN)

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syndromes  Multiple endocrine & other organ neoplasia syndromes  Autoimmune

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polyendocrine syndromes (APS)

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Diabetes Mellitus 42
Acute complications: DKA & HHS  Management of diabetes mellitus  Classification
of diabetes  Type 2 DM  Diagnosis  LADA, KPD and MODY  Type 1 vs. Type 2
DM  Metabolic syndrome  Effect of incretins

Calcium Metabolism and Thyroid Disorders 52

Calcium  Hypercalcemia  Hypocalcemia  Phosphorous  Thyroid hormone
synthesis  Thyroid disorders  Clinical presentation of thyroid disorders

Heart Failure and Cardiomyopathies 60

Heart failure  Presentation  Causes & response
mechanisms  Treatment  Cardiomyopathies  Dilated cardiomyopathy  Hypertrophic
cardiomyopathy  Restrictive cardiomyopathy  Takotsubo cardiomyopathy

Pericarditis & cardiac tamponade 71

Chronic constrictive pericarditis vs. Restrictive cardiomyopathy vs. Tamponade

Arterial Pulses, JVP and Heart Sounds 73

Arterial pulse  Abnormalities of pulse  Jugular venous pulse  Abnormalities 
Valvular heart disease : findings  Heart sounds  First heart sound (s1) 
Second heart sound (s2)  Diastolic added sounds  Systolic added sounds
Valvular Heart Disease 81
Comparison of valvular diseases  Mitral valve prolapse (MVP)

ECG Revision 86
ACS  IWMI  AWMI  Tachyarrhythmia  Atrial fibrillation

Gastrointestinal Disorders 93
Inflammatory bowel disease  Ulcerative colitis vs. Crohn's disease 
Malabsorption  Pseudomembranous enterocolitis  Celiac disease 
Whipple's disease  Tropical sprue  Irritable bowel syndrome (IBS)

Hepatic Disorders 105

Anatomy  Cirrhosis  Acute hepatitis  Hepatic failure  Chronic hepatitis 
Portal hypertension  Ascites  Hepatic encephalopathy  Hepatitis B  Hepatitis C 
Autoimmune hepatitis  PBC vs. PSC  Haemochromatosis & wilson’s disease

Basics of pulmonology : Structure, Mechanics & PFT 117

Bronchi vs. Bronchiole  Major lung diseases  Alveoli  Classification of lung diseases 

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Mechanics of breathing  Obstructive lung diseases  Restrictive lung diseases 

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Approach to lung disorders

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Vascular Disorders of Lung  122
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Venous thromboembolism/pulmonary thromboembolism  Pulmonary hypertension
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Obstructive Lung Diseases 126

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Bronchiectasis  Pulmonary eosinophilia (eosinophilic lung

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disease)  ABPA  Hypersensitivity pneumonitis (HP)  Bronchial

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asthma  Management  COPD  Chronic bronchitis vs. Emphysema  Types of

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respiratory failure  Management of COPD

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Restrictive Lung Diseases 137

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Classification  Features  Management  Types of pneumoconiosis 

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Chronic silicosis, CWP & asbestosis

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ARDS, Pneumonia & Pleural Effusion  143

Acute respiratory distress syndrome (ARDS)  Management of pneumonia 
Pleural effusion

Cortical and Subcortical Lesions 147

Frontal lobe lesions  Parietal lobe lesions  Temporal lobe lesions 
Occipital lobe lesions  Dementia  Alzheimer’s disease (AD) 
Other dementias  Subcortex  Parkinson’s disease  Parkinson’s plus syndrome

Neuropathies157
LMN  Radiculopathy, plexopathy & ganglionopathy  Types of neuropathies 
Types  Charcot marie tooth disease : type 1  Guillain-barre syndrome (GBS)

Headache and Seizures 162

Headache  Tension type headache and migraine  Trigeminal autonomic cephalgias 
Trigeminal neuralgia  Seizure : Focal  Generalized seizure  Status epilepticus (SE)
Approach to Stroke 169
MCA lesion  PCA and ACA lesions  Stroke and TIA  Management of
stroke  Brainstem lesions

Neuromuscular dysfunction & Spinal Cord Diseases 175

LMN : Pure motor presentation  Myasthenia gravis  Motor neuron disease (MND) 
Spinal cord (SC)  Myelopathy

Basics of Hematology 181

Stem cells  Hematopoiesis  Evaluation of anemia

Approach to Anemia : Part 1 184

Iron - absorption, RDA and distribution  Anaemia of chronic disease  Comparison of
anaemias  IDA  Sideroblastic anaemia  Macrocytic anemia  Non-megaloblastic
macrocytic anemia  Megaloblastic macrocytic anemia  Vitamin b12 deficiency  Folic
acid (FA) deficiency

Approach to Anemia : Part 2 195

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Hemolysis  Immune hemolysis  Enzymopathies  Paroxysmal nocturnal

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hemoglobinuria  Fragmentation hemolysis  Bone marrow failure syndromes

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Myeloproliferative Neoplasms 203
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Features and types  Approach to polycythemia  Polycythemia rubra vera (PCRV) 
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Primary myelofibrosis  Essential thrombocytosis  Chronic myeloid leukemia (CML)

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Acute Myeloid Leukemia 209

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Basics of AML  Classification and diagnosis  Management 

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Acute promyelocytic leukemia (APML)

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Lymphoid Series Neoplasms  213

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B-cell maturation & neoplasms  T-cell neoplasms  Virus associations of lymphomas 

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Acute lymphoblastic leukemia (ALL)  Chronic lymphocytic leukemia (CLL) 

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Lymphomas  Non hodgkin lymphoma (NHL)  Memory B - cell disorders

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Plasma Cell Disorders 222

Multiple myeloma  Waldenstrom macroglobulinemia and POEM syndrome

CKD  225
Anatomy of kidneys  Etiopathogenesis of CKD  Staging and diagnosis

Tubular Disorders 228

Type 2 RTA  Type 1 RTA  Type 4 RTA  Bartter syndrome  Gitelman syndrome 
Hypo & hyperkalemia

Glomerular Disorders 234

Clinical presentation  Nephrotic syndrome (NS)  Acute glomerulonephritis (GN) 
Podocytopathy  Glomerulonephropathy  RPGN

Approach to Renal Failure & Acute Kidney Injury 241

Secondary hypertension  Vascular kidney disease  Pre-renal AKI vs ATN 
Drugs causing AKI
Connective Tissue Diseases : Part 1 245
Sjogren’s syndrome  Extraglandular sjogren manifestations

Connective Tissue Diseases : Part 2 251

IgG4 related diseases  Sarcoidosis  Behcet’s disease

Rheumatology : Rheumatoid arthritis and Systemic Lupus Erythematosus 259

Rheumatoid arthritis (RA)  Systemic lupus erythematosus (SLE) 
Systemic manifestations of SLE and RA  Management  IF patterns in autoimmune
diseases

Systemic Sclerosis and Inflammatory Muscle Disease 267

Types of SSc  Raynaud’s phenomenon  Treatment  Inflammatory muscle
disease  Dermatomyositis & polymyositis  Skin manifestations in dermatomyositis

Vasculitis 274
Classification of vasculitis  Large vessel vasculitis  ANCA mediated small vessel vasculitis 
GPA vs. MPA vs. EGPA vs. PAN  Immune complex mediated small vessel vasculitis

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Spondyloarthropathies 281

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Axial predominant spa  Peripheral predominant spa  Crystal arthropathies
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 Basics Of Pituitary Gland 1

BASICS OF PITUITARY GLAND ----- Active space -----

Anatomy 00:01:54

Development :
• Anterior pituitary :
Upgrowth from roof of surface/oral ectoderm (Rathke’s pouch).
• Posterior pituitary :
Downgrowth from floor of 3rd ventricle (Neuroectodermal).

Applied anatomy :

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Congenital hypopituitarism :

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PROP 1 mutation (Transcription factor)

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Pituitary dysplasia (Only anterior pituitary)
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Midline craniofacial abnormalities (D/t defective

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migration of Rathke’s pouch) :

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• Anencephaly. • Single central incisor.

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• Optic abnormality. • Cleft lip & cleft palate.

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Gross Features :
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Weight :
• Normal : 600 mg. • Pregnancy : > 1 g.

Dimensions : 6 mm x 12 mm.

Pituitary Cells And Hormones 00:05:11

Hormones of anterior pituitary

Medicine • World of Revision • v2.0 • Marrow • 2025
 2 Medicine

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

Percentage
Cells Hormones Features
of gland
Somatotrophs > 50% GH (191 a.a.) Twin hormones :
• Polypeptides.
• Acidophilic cells.
• Pathway : JAK-STAT.
• Location : Anterolateral
Lactotrophs
Acidophilic
(Develop last : > 15% Prolactin (199 a.a.)
Vulnerable to ischemia d/t
24 weeks)
vascular insult :
- Sheehan’s syndrome.

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- Viper bite.

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- Sickle cell anemia.

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Thyrotrophs < 5% TSH • Scattered throughout gland
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• FSH • Glycoproteins
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Gonadotrophs 10%
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• LH • Same α subunit
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POMC
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(Pro-opiomelanocortin)
Basophilic • Polypeptides
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Corticotrophs
• Endorphins :
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(Develop first : 10% • ACTH.

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- Natural pain killers

6 weeks)
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• MSH.
- μ receptor agonists
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• β-lipotrophins
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Endorphins.

Note :
Hormones of happiness (DOSE) : Dopamine, Oxytocin, Serotonin, Endorphins.

Transcription Factors of Pituitary Development :

Mutation of transcription factor genes

Pituitary dysplasia

Congenital hypopituitarism.

Medicine • World of Revision • v2.0 • Marrow • 2025

 Basics Of Pituitary Gland 3

Transcription Cell types ----- Active space -----

Features
factor genes developed
All cells except Enlarged
PROP 1 : M/c
gonadotrophs gland
• Thyrotrophs
PIT 1
• Lactotrophs
(2nd m/c) Atrophic
• Somatotrophs
gland
TPIT Corticotrophs
GATA 2 Gonadotrophs
Septo-optic
HESX 1
dysplasia
Early gland
Rigid
development
LHX 3 cervical

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Genes of pituitary gland development

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Hypothalamo-Hypophyseal System
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Adenohypophyseal Relation :
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Superior hypophyseal artery

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Hypothalamus Hypothalamo-hypophyseal
portal system :
Tubuloinfundibular pathway : +
- • GHRH GH.
Dopamine Prolactin +
(Prolactin inhibitory factor : PRIF) • TRH TSH.
+
• CRH ACTH.
+
• GnRH FSH, LH.
Anterior pituitary

Medicine • World of Revision • v2.0 • Marrow • 2025

 4 Medicine

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

Stalk effect :
• Pituitary adenoma : Enlarged gland.
• Lymphocytic hypophysitis : Inflammatory mass.

Compress stalk

↓ACTH, TSH, FSH, LH ↑Prolactin (↓Dopamine)

Hypopituitarism with hyperprolactinemia.

Neurohypophyseal Relation : Hypothalamus-pituitary

Hypothalamus : Magnocellular neurons in the
supraoptic & paraventricular nuclei produce ADH & oxytocin

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Axons of pituitary stalk

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Posterior pituitary : Inferior hypophyseal artery :

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Hormones stored. Route of metastasis.
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• M/c primary : Ca breast.
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• M/c manifestation :
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Posterior pituitary insufficiency (↓ADH).

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Pituitary Imaging And Relations 00:29:28

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MRI Appearance :
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Precontrast :
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• Anterior pituitary : Isointense/hypointense.

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• Posterior pituitary : Bright spot Absent bright spot : 80% specificity for central DI
(AKA AVP-D : Arginine vasopressin deficiency).
Postcontrast : Uniform uptake.

T1 sagittal section MRI : Absent bright spot

Precontrast normal pituitary

Medicine • World of Revision • v2.0 • Marrow • 2025

 Basics Of Pituitary Gland 5

Relations To Other Structures : ----- Active space -----

Pituitary mass Hormonal effect (Functional tumors).

Mass effect.
Stalk effect.
Posteriorly : 
Sella turcica (Inside sphenoid sinus).
Approach through
Transsphenoidal endoscopic surgery :
TSS (↓Risk of permanent post-op hypopituitarism)
Lateral :
TSS of pituitary adenoma
Cavernous sinus : Temporal lobe.
• Internal carotid artery

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• CN - III, IV, V1, V2, VI

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Ventral : 
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Diaphragma sella (Dura) : Stalk compression (Initial) ↑ICT symptoms
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Least resistance
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Optic chiasma :
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(Most expansion)
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Heteronymous hemianopia (Bitemporal).

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Medicine • World of Revision • v2.0 • Marrow • 2025

 6

----- Active space ----- ANTERIOR PITUITARY DISORDERS : PART 1

Prolactin 00:00:29

Function & regulation :

+
Estrogen, TRH, VIP,oxytocin
Prolactin Induces & maintains lactation
Dopamine in primed breast.
-
Other sources :
• CNS.
• Uterus.

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• Placenta.

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Hyperprolactinemia : 56
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• Bioactive form : Microprolactin/little prolactin (23 kDa).
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• Investigation : Enzyme immuno assay in fasting (EIA).

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• Primary hypothyroidism ↓T3, T4 ↑TSH, ↑TRH Hyperprolactinemia.

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Prolactin Condition Cause

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< 25 µg/L (ng/mL) Normal -

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•Sleep (REM)
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•Stress
25 - 40 µg/L Physiological ↑ •Pregnancy (40 - 200 µg/L)
•Lactation
•Chest wall stimulation
•Drugs : D2 receptor blockers
•Stalk effect/neurogenic tumor effect :
Craniopharyngioma
• Systemic disorders :
40 - 100 µg/L
- PCOS
Pathological ↑
- Hypothyroidism
- Chronic kidney disease
- Chronic liver disease
> 100 µg/L Very likely adenoma
> 200 µg/L Confirmed adenoma

Medicine • World of Revision • v2.0 • Marrow • 2025

 Anterior Pituitary Disorders : Part 1 7

Drug induced : ----- Active space -----

Block D2 receptors :
• Chlorpromazine • Metoclopramide :
• Thioridazine Anti-emetic (Crosses BBB).
• Haloperidol Typical antipsychotics. • TCA/SSRI.
• Triflupromazine • Opiates.
• Flupentixol • Verapamil.
• Risperidone : • H2 blockers.
- Atypical antipsychotic. • α-methyl dopa.
- Prolactin (> 200 µg/L).

Macroprolactinemia :
• Falsely ↑prolactin : Tested by EIA.

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• Asymptomatic.

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• Macroprolactin (Inactive) identified by gel precipitation.

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Pituitary Adenoma @ 00:13:39
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Types :
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Based on function :
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Functional : Non-functional (M/c) :

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• Prolactinoma (M/c) : • Tumors producing α subunit of

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25 - 45 yrs. FSH > LH > TSH.

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• GH secreting : > 40 yrs. • Null cell adenoma :

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• ACTH secreting. - Immunohistochemically negative.

- E.g. : Craniopharyngioma,
Rathke’s cyst, germ cell tumor.
Based on size :

< 1 cm 1 - 4 cm > 4 cm
only 5%
Microadenoma : Macroadenoma : Giant adenoma.
• Prolactinoma GH secreting adenoma
• ACTH secreting
adenoma < 20 yrs

• Familial syndromes.
< 20 yrs
• McCune Albright syndrome
(Post zygotic mutation : Gsα subunit).
Medicine • World of Revision • v2.0 • Marrow • 2025
 8 Medicine

----- Active space ----- Familial Pituitary Tumor Syndromes :

Syndrome Mutation
MEN 1 Menin gene
MEN 4 CDKN 1B
Carney’s complex PRKAR 1a
Familial isolated pituitary adenoma AIP

Prolactinoma 00:18:49

M/c functional pituitary tumor.

Sex :
• Microprolactinoma = 20 : 1

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• Macroprolactinoma = 1 : 1 Female : Male.

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Age : 25 - 45 years.
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Presentation :
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↓HPG axis : Hypogonadism symptoms

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Females : Males :
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• Galactorrhea. • Loss of libido

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Less common; present

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• Secondary amenorrhea. • Erectile dysfunction

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with mass effect

• Gynecomastia
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• Infertility.
(Headache).
• Menstrual irregularities.
• Hot flushes, vaginal dryness.

↓Bone mineral density : Spinal fracture.

Insulin resistance.

Compression of surrounding structures :

• 45% : Stalk effect.
• 35% : Visual field symptoms.

Hook effect :
• Falsely ↓prolactin.
• Large tumor present.
• Test repeated with serial dilution.

Medicine • World of Revision • v2.0 • Marrow • 2025

 Anterior Pituitary Disorders : Part 1 9

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

• Fasting S. prolactin.
• IOC : Gd enhanced MRI (T1 precontrast & postcontrast).

Microadenoma (Precontrast) : Microadenoma (Postcontrast) : Pituitary macroadenoma :

• Gland asymmetry. Flip-flop (Delayed uptake) : Heterogenous :
• Loss of superior concavity. • Adenoma : Hypointense. • Solid : Hyperintense.
• Stalk deviation. • Gland : Hyperintense. • Cystic : Hypointense.
• Sella floor depression.

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Treatment :
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Asymptomatic microadenomas Symptomatic microadenoma/

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Macroadenoma
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Follow up :
• 3 monthly prolactin level. Medical Rx
• 6 monthly MRI.

4 weeks
20%
• Prolactin ↑ • Prolactin ↑ Prolactin ↓
• No S/e • S/e present

Increase dose. Dopamine agonist resistance Continue Rx

(Max 2 years)
Surgery 3 - 6 months

Radiotherapy if unfit. Repeat MRI :

Shrinkage of tumor.

Medicine • World of Revision • v2.0 • Marrow • 2025

 10 Medicine

----- Active space ----- Dopaminergic agonist :

Cabergoline (DOC) :
• + D2 receptor.
• Long half life (Weekly dose).
• ↓Side effects : Vomiting, dizziness, postural hypotension.
• Impulse control disorder in 5% (Also in Bromocriptine).
• Starting dose : 0.25 mg twice weekly (Max. dose : 2 mg/week).
• > 4 g/week : Risk of ILD and tricuspid regurgitation.
Surgery indications :
• Dopamine agonist resistance.
• Pituitary apoplexy (Bleeding into gland).
• Persistent visual field defects (Despite 4 weeks medical Rx).
• ↑Size during pregnancy.

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Pregnancy :

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Medical Rx before pregnancy
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↓Symptoms : Ovulatory cycles

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Conception • Stop Rx.

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• Cabergoline : Only if visual field defects.

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Pregnancy • TSS : Persistent symptoms in 2nd trimester.

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Macroadenoma :
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Microadenoma :
2% risk of progression. 30% risk of progression.
Lactation : Drugs not used.

Note :
• Marker for prolactinoma malignancy : Ki-67.
• No role in checking prolactin levels in pregnancy.

Growth Hormone 00:39:51

Somatotrophs :
• 50% of all cells : Affected by stalk compression
M/c deficiency : GH.
• Present anterolaterally : Prone to ischemia

Functions :
IGF-2 : Intrauterine growth.
Medicine • World of Revision • v2.0 • Marrow • 2025
 Anterior Pituitary Disorders : Part 1 11

GH & IGF-1 : ----- Active space -----

Action on IGF-1 GH
Proteins Anabolic
Lipolytic : ↑FFA
Fats Anti-lipolytic
(↑Insulin resistance)
Carbohydrates Antidiabetogenic Diabetogenic
Na+-H2O retention - ↑

Direct action of GH (Independent of IGF-1) :

• Bone growth.
• Epiphyseal fusion.
• Adipose : Lipolysis.

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• Muscle protein synthesis.

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• Sodium-H2O retention.

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Regulation : @
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• Hypoglycemia
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• GHRH, ghrelin
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Hypocaloric (Malnutrition)
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• 2 & 4 stage +
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Resistance
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NREM sleep
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GH
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- Decreases
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Somatostatin Obesity, ageing

In obese children :
• GH : ↓
• Growth↑ : D/t other hormones stimulating IGF-1 release.

Action of TRH :
TRH No action Normal gland.

+ +
GH secreting adenoma ↑↑GH.
GH Deficiency :
Laron dwarfism :
• Mutation of liver GH receptor ↓IGF-1 production.
• ↑↑GH, ↓IGF-1.
Laron’s dwarfism
Medicine • World of Revision • v2.0 • Marrow • 2025
 12 Medicine

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

Measurement Of GH :
Estimation using IGF-1 : Indirect estimation.
Growth hormone : GH receptor Liver Produce IGF-1/Somatomedin-C
• t½ : 5 - 20 mins. (Insulin like growth factor)
• Pulsatile release.
Binds to IGF binding protein-3
Testosterone, estrogen,
thyroid hormone, insulin T1/2 of complex : 12 - 15 hrs

Levels tested in GH imbalance.

GH provocation tests :
• Gold standard for GH : Insulin tolerance test.
• GH enhancers for stimulation tests :

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- Arginine. - Clonidine.

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- L-dopa. - GHRH.
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- Glucagon. @
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Acromegaly
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00:53:12
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GH Secreting Adenomas :
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• 20% a/w somatomammotropic adenomas : Hyperprolactinoma.

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• <20 yrs : A/w familial syndromes (MEN-1), McCune Albright syndrome.

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Causes :
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Acromegaly (98%) : Other causes :

• Macroadenomas. • Ectopic GH secretion : Pancreatic islet
• Age : >40 yrs. cell tumor.
• M > F. • GHRH secreting hypothalamic tumor :
Hamartoma.
• Ectopic GHRH production :
- Bronchial carcinoid.
- Small cell lung Ca.
- Medullary thyroid Ca.
Types :

Densely granulated : Sparsely granulated :

Eosinophilic cells. • Chromophobe cells.
• Poor prognosis.
Medicine • World of Revision • v2.0 • Marrow • 2025
 Anterior Pituitary Disorders : Part 1 13

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

Reticulin network Lost Pituitary adenoma.
Intact Pituitary hyperplasia.

Clinical Features :
Features
• Thickening of lips
• Macroglossia
• Prominent supraorbital ridge
Coarse facies • Thick nose
• Jaw malocclusion
• Prognathism
• Frontal bossing

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• ↑Hand size

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Body Soft tissue swelling

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• ↑Feet size
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Eye @
Angle closure glaucoma
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Nerve Carpal tunnel syndrome (Compression neuropathy)

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Muscle Myopathy (Type 2 fibre atrophy)

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Respiratory Obstructive sleep apnea syndrome

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Acromegalic cardiomyopathy (M/c cause of mortality) :

|
w

• HFpEF
ro
ar

CVS • ↑Coronary artery disease

M

• Hypertension
©

• LVH
GIT Colonic polyposis Malignant
• Insulin resistance, diabetes
Metabolic • Hypertriglyceridemia
• Hypercalciuria : ↑1α-hydroxylase (↑Ca2+,↑PO43-)
• Hyperhidrosis
Skin
• Seborrhea
Joints Arthralgia Arthritis
Stalk effect Hypopituitarism with hyperprolactinemia
• Oligomenorrhea
GUS
• Na+ - H2O retention
Thyroid Thyromegaly (Asymptomatic)

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 14 Medicine

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

Symptoms for high activity : DOSA.
• DM. • Seborrhea.
• OSAS. • Arthralgia.

Coarse facial features Large hands McCune Albright syndrome :

• Asymmetrical face
• Polyostotic fibrous dysplasia

om
l.c
Pseudoacromegaly :

ai
gm
• Facial features of acromegaly in absence of tumor.
@
• Causes :
56
t4

- Obesity.
chi
ra

- Hypothyroid.
al
aw

- Phenytoin.
r
ag

- IGF-2 tumors.
|

- Insulinoma.
w
ro
ar

Investigations :
M
©

Screening : Random IGF-1 level

Normal Equivocal Increased

Acromegaly Glucose induced GH suppression IOC : Gd enhanced MRI.

ruled out. test (Confirmatory) :
75 g oral glucose

GH levels : 30 min, 60 min,

90 min, 120 min

All 4 results : < 1 ng/mL All results : ≥ 1 ng/mL

(Inability to suppress GH)

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 Anterior Pituitary Disorders : Part 1 15

MRI : ----- Active space -----

Heterogeneous uptake :
• Solid component :
Enhancement with
contrast.
• Cystic component :
No enhancement.

Pituitary function tests :

• Prolactin.
• LH, FSH.
• ACTH : Insulin tolerance Postcontrast T1 : Macroadenoma
test.
• TSH.

om
l.c
ai
Treatment :

gm
Surgery : @ N
56
Immediately
TSS (TOS) post-op/next GH : < 1 ng/mL For 12 weeks • IGF-1 Cured.
t4

day
hi

• MRI
c
ra

Not N
al
aw

Medical Rx > 2nd surgery.

r
ag
|

If patient unfit for surgery : Radiotherapy.

w
ro
ar

Somatostatin receptor ligands : GH receptor antagonist :

M

• Drugs : • Pegvisomant.
©

- Octreotide. • ↑GH, ↓IGF-1.

- Lanreotide. • Mandatory LFT monitoring.
- Pasireotide
Other :
(Selective for SSTR5).
Cabergoline : ↓Prolactin (If high).
• Route : Deep S/C.
• Receptors : SSTR2, SSTR5.
• S/e :
- Abdominal cramps.
- Gall stones.
- Diarrhea.
- Worsen DM.

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 16

----- Active space ----- ANTERIOR PITUITARY DISORDERS : PART 2

Non-functional Tumors 00:00:35

Craniopharyngioma Rathke’s cyst Germ cell tumors

Craniopharyngioma vs. Rathke’s Cyst :

Craniopharyngioma
Rathke’s cyst
Childhood : 90% Adulthood : 10%

om
5 - 15 years

l.c
Age 50 - 74 years 40 - 50 years
(M/c pituitary tumor)

ai
gm
Mutation β-catenin (CTNNB 1) BRAF -
@
56
Gender M>F M=F -
t4
hi

• Cystic (Machinery oil

• Unilocular
c
ra

appearance) > Solid

Appearance & • Nodules +
al

• Wet keratin nodules + Solid

aw

clinical features • Protein and cholesterol

• C/f : Central diabetes
r
ag

crystals
insipidus (Stalk effect)
|
w

Location Suprasellar (Infundibulum) Sellar Sellar

ro
ar

Histology Adamantinomatous Papillary Columnar epithelium

M
©

Calcifications + - -
Precontrast Hypointense Hyperintense : White on T1
MRI Claw sign/posterior ledge sign/
appearance Postcontrast Vivid enhancement (Cyst wall uptake) nodule inside/dot sign :
Contrast taken up by margins

Hypointense lesions Vivid enhancement

Calcifications Precontrast MRI : Craniopharyngioma Postcontrast : Craniopharyngioma

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 Anterior Pituitary Disorders : Part 2 17

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

Precontrast : Rathke’s cyst Postcontrast : Rathke’s cyst (Claw sign)

Germ Cell Tumors :
Largeloculated supracellar mass Obstructive hydrocephalus.
(Within 3rd ventricle)

MRI Appearance of Functioning vs. Non-functioning Tumors :

om
l.c
Rathke’s cell

ai
Microadenoma Macroadenoma Craniopharyngioma

gm
cyst
T1 : Pre contrast Hypo to isointense @
Hypo to isointense Hypo to isointense Hyperintense
56
t4

Flip-flop mechanism :
hi

Heterogenous
c

T1 : Post contrast Delayed enhancement Vivid enhancement Claw sign

ra

enhancement
of tumor
al
raw
ag

Note :
|
w

Classical signs of brain lesions :

ro
ar

• Calcification/bony hyperostosis/pneumosinus dilatans : Meningioma.

M

• Notochordal remnant with clivus destruction : Chordoma.

©

• Ring enhancing lesion : Pituitary abscess.

• Stalk thickening (MD LAST - Mnemonic) :
Metastasis, Dysgerminoma, Langerhans cell histiocytosis (LCH), Astrocytoma,
Sarcoidosis, Tuberculosis.
• Gland enlargement + stalk thickening : Lymphocytic hypophysitis (LH).

Acquired Hypopituitarism 00:08:22

Causes :
Stalk effect
Vascular insult
(Hypopituitarism + hyperprolactinemia)
• Tumors
• Sheehan syndrome
• Trauma/surgery
• Sickle cell anemia
• Infections : HIV, toxoplasmosis, pneumocystis, histoplasmosis, TB (Rare)
• Snake bite (Viper)
• Infiltrative : LCH, LH, sarcoidosis, hemochromatosis.

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 18 Medicine

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

FSH/LH deficiency : TSH deficiency (Least apparent) :
Hypogonadism with premature aging : • Cold intolerance.
• ♀ : Hot flushes, amenorrhea. • Bradycardia.
• ♂ : Loss of muscle mass, bone mineral • Constipation.
density (BMD) & 2˚ sexual characters.

Growth hormone deficiency : ACTH deficiency (In acute

• Endothelial injury Thrombosis. hypopituitarism) :
• ↓BMD, ↓muscle mass Altered fat • Hypoglycemia
to muscle ratio. • Hypotension D/t
• ↓Quality of life ↑Triglycerides. • Hyponatremia cortisol
(Euvolemic) deficiency.
Note :

om
• Fatigue
Effects of aldosterone insufficiency :

l.c
ai
• Salt craving
gm
Not seen in hypopituitarism@
• Hyperkalemia
56
(Aldosterone : RAAS control).
• Dehydration
t4
chi
ra

Pituitary Apoplexy
al

00:18:12
raw

Acute intra-pituitary hemorrhage (Endocrine emergency).

ag
|
w

Causes :
ro
ar

• Adenoma.
M
©

• Infarct.
• Spontaneous : Diabetes mellitus/hypertension/sickle cell anemia.
Clinical features :
Acute presentation (1 to 2 days) with :
• Severe headache ± meningeal signs. • Hypotension.
• Ophthalmopathy. • Hyponatremia.
• Hypoglycemia.

Mx :
• IV steroids.
• Decompressive surgery if :
- ↓Consciousness.
- ↓Visual acuity/Visual field
Pituitary apoplexy
defects.

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 Anterior Pituitary Disorders : Part 2 19

Sheehan Syndrome vs. Lymphocytic Hypophysitis 00:20:34 ----- Active space -----

Sheehan syndrome Lymphocytic hypophysitis

Postpartum pituitary necrosis :

↑Gland size & vascular demand (Pregnancy) Antibody mediated inflammation (IgG4) of
PPH : Hypotension, gland
Pathophysiology DIC
↓Blood flow Mass effect on stalk
(Stalk effect).
Pituitary necrosis

• Early presentation :
- Lactational failure
• Pituitary enlargement
- ACTH deficiency
• Headache & visual disturbance
• Late presentation :
• Hypopituitarism

om
Clinical features - 2˚ amenorrhea
• Hyperprolactinemia

l.c
- Hypogonadism (Premature aging)

ai
• Associated autoimmune diseases

gm
- Diabetes insipidus
• Diabetes insipidus
- Anemia Rare @
56
- Psychiatric disturbances
t4
hi

• Anterior pituitary hormones : ↓ • ACTH, TSH & ADH :↓

c
ra

Hormonal profile
• ADH : Normal • Prolactin : ↑↑
al
aw

Mass with stalk thickening :

r
ag

Pituitary MRI Empty/severely damaged sella turcica

Contrast enhancement seen
|
w

Rx Hormone replacement Steroids

ro
ar
M
©

a. Premature aging b. Empty sella c. Pituitary mass & d. Contrast enhanced

stalk thickening

Note :
• Empty sella :
- 1˚ : Benign intracranial hypertension (No hypopituitarism).
- 2˚ : Tumor, infarct (Hypopituitarism + ).
• Test for pituitary sufficiency :
GH and ACTH Insulin tolerance test (Gold standard).
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 20 Medicine

----- Active space ----- POSTERIOR PITUITARY DISORDERS

Anti-diuretic Hormone (ADH)/AVP 00:02:49

Stimuli for Production :

1. ↑Serum osmolality > 285 mOsm/kg :

S. osmolality = 2 x S. Na+ + Blood glucose + BUN (Blood urea nitrogen)

18 2.8
Major contributor
• ↓S. osmolality ↓ Na (True hyponatremia).

om
• ↑S. osmolality ↑ Na.

l.c
ADH & thirst

ai
(Prevent hypernatremia)

gm
2. ↓Effective arterial volume. @
56
t4
chi
ra
al
raw
ag
|
w

290
ro
ar
M
©

Response to change in serum osmolality

ADH Receptors & Actions :

IP3/DAG pathway cAMP pathway

V1 receptors : V3/V1b receptors : V2 receptors :

• Vasoconstriction. ↑ ACTH release from • ↑vWF release from endothelial
• Platelet aggregation. anterior pituitary. cells : Desmopressin used in
• Glycogenolysis. Von willebrand disease.
• Collecting duct.
Note :
↓ Water intake ↑ ADH Myocardial hypertrophy.

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 Posterior Pituitary Disorders 21

Action on kidneys : ----- Active space -----

a. Free water reabsorption :
ADH

V2 receptors (Basolateral membrane of collecting duct cells)

↑ cAMP and protein kinase A (PKA)

↑ Stored aquaporins (AQP-2) ↑ Urea transporter (UTA1)

Free water reabsorption. Urea entry into cell.

om
l.c
ai
UT-A1

gm
@
56
PKA
t4
chi

AQP2
ra
al
raw
ag
|
w

ADH action on collecting duct

ro
ar
M
©

b. Component of counter current exchange :

ADH Vasa recta

Urea reabsorption from CD Prevents urea washout

↑Urea in interstitium

Medullary hyperosmolarity
maintained

Used by ADH for H2O

reabsorption

↑Urine osmolality
(800 - 900 mOsm/kg). Urine osmolality (mOsm/kg) changes along nephron
Medicine • World of Revision • v2.0 • Marrow • 2025
 22 Medicine

----- Active space ----- AVP Deficiency/Central DI 00:14:23

Causes :
1. Compression of pituitary stalk
above median eminence :
• Tumour :
- Craniopharyngioma
(Large suprasellar tumour).
- Metastases.
- Germ cell tumours.
• Infiltrative :
- Sarcoidosis.
Pituitary stalk
- Langerhans cell histiocytosis (LCH).

om
l.c
Note :

ai
gm
Compression of stalk below median eminence :
ADH released proximally through portal capillaries@ No deficiency.
56
t4
hi

2. Trauma/surgery (M/c) :
c
ra

Triphasic response (D/t transection of stalk) :

al
raw

DI (First 3 - 6 days)
ag
|

Stored ADH release

w

​
ro

SIADH (Lasts 5 - 7 days)

ar
M
©

DI (Transient/Permanent).
Triphasic response
3. Autoimmune :
• Lymphocytic hypophysitis (LH) : IgG4 related disease.
• Autoimmune polyendocrine system - I (APS-I).

4. Inherited (5%) :
• AD > AR
• Autosomal recessive : DI DM OA D Syndrome.
(3) (1) (2) (4) : Order of occurrence.
- DI. - Optic atrophy.
- DM. - Deafness.

5. Pregnancy : Vasopressinase (Placenta) Breakdown Vasopressin .

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 Posterior Pituitary Disorders 23

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

1. Polyuria : > 50 mL/kg/24 hours or > 3 L/day.

2. Nocturia.
3. Polydipsia :
- Prevents hypernatremia.
- Exception : Adipsic hypernatremia.
Absent thirst (Defective osmoreceptors) Central DI with hypernatremia.

Polyuria 00:26:23

Urine osmolality :

< 300 mOsm/kg 300 - 600 mOsm/kg > 600 mOsm/kg

om
l.c
< 1000 > 1000
Water diuresis/ Solute diuresis

ai
Total daily solute excretion :

gm
hypotonic polyuria : U. osmolality x 24hr urine volume
56
@ (Ruled out first) :
• AVP-d. (In L) • Diabetes mellitus.
t4

• AVP-r (AVP resistance)/

hi

• SGLT-2 inhibitors.
c
ra

nephrogenic DI. • Mannitol.

al
aw

• Psychogenic polydipsia. • Steroids.

r
ag

• Post obstruction.
|
w

AVP Resistance/Nephrogenic DI
ro

00:30:38
ar
M

Causes :
©

1. Tubulointerstitial fibrosis (CKD) : Mild form.

2. Drugs :
• Lithium : AQP-2 dysfunction. • Foscarnet.
• Demeclocycline. • Cidofovir.
• Cisplatin. • Ifosfamide.
3. Electrolyte abnormalities :
• Hypercalcemia. • Hypokalemia.
4. Autoimmune conditions :
• Sjogren’s syndrome. • IgG4 related disease.
• Sarcoidosis (Hypercalcemia)
5. Pregnancy.
6. Inherited : Congenital nephrogenic DI.
X-linked (V2 receptor mutation) > AR (AQP-2 mutation).
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 24 Medicine

----- Active space ----- Management of DI 00:34:11

Investigations :
1. Plasma copeptin assay :

> 21.4 pmol/L (Normal) < 21.4 pmol/L

Nephrogenic DI/AVP-r. Arginine stimulation test

↑ Copeptin level : No change (< 3.8 pmol/L) :

Psychogenic DI. Central DI/AVP-d.

2. Water deprivation test :

Fasting :

om
• Overnight : If u. osmolality > 100

l.c
• 2 - 3 hrs : If u. osmolality < 100

ai
gm
@
56
Check u. osmolality (mOsm/kg)
t4
chi
ra

> 600 < 600

al
raw

Psychogenic DI. Desmopressin (Intranasally)

ag
|
w

Check U. osmolality every 30 minutes x 4 times

ro
ar
M

100%↑ and > 300 mOsm/kg < 15%↑ and < 300 mOsm/kg
©

Central DI/AVP-d. Nephrogenic DI/AVP-r.

Treatment :
1. Central DI :
• Desmopressin.
• Thiazide diuretics.
• Low solute diet.

2. Nephrogenic DI :
• Thiazide diuretics : DOC.
• Amiloride :
- DOC for lithium induced DI.
- Blocks ENaC.

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 Posterior Pituitary Disorders 25

Antidiuretic Hormone (ADH) 00:45:59 ----- Active space -----

Appropriate ADH Release :

Stimulus :
1. ↑Serum osmolality (> 280 mOsm/L).
2. ↓Effective intravascular volume.

Inappropriate ADH Release :

Syndrome of inappropriate ADH secretion (SIADH)

↓Free water clearance

om
↓Urine volume (Concentrated urine)

l.c
ai
gm
↑Urineosmolality ↑Total@ body water (TBW)
56

(Urine Na > 40 mEq/dL)

+
t4
chi
ra

↑Natriuretic peptides Hyponatremia

al

(S. Na+ ∝ 1 )
aw

TBW
r

Euvolemia.
ag
|

↓S. osmolality
w
ro

(No thirst).
ar
M
©

Note :
Normal saline is not used in the Mx of SIADH (↑TBW).

Hyponatremia 00:56:26

Disorder of water metabolism.

Mechanisms preventing hyponatremia :

1. Absorption in the PCT is isosmotic.
2. Only Na+ is reabsorbed in the thick ascending limb & DCT.
3. Baseline ADH level is low/negligible.

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 26 Medicine

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

Causes of Hyponatremia :
Based on S. osmolality

True hyponatremia(↓Tonicity/↓S. Na+) Pseudohyponatremia

(↑/ N tonicity) :
1. ↑Effective osmoles :
Appropriate ADH stimulation Inappropriate ADH Solutes like glucose/mannitol
(↓Effective intravascular stimulation
volume) Do not enter the cell
Euvolemic hyponatremia : ↑Effective osmolality/tonicity
• SIADH.
• Cortisol & thyroid Translocation of water into
intravascular space.

om
deficiency.

l.c
2. Laboratory error :

ai
gm
- Due to paraproteinemia/
Hypovolemic hyponatremia : Hypervolemic hyponatremia : @ hypertriglyceridemia/IVIG.
56
D/t fluid loss • ↑Fluid in extravascular
t4

- Can be seen with

hi

space.
c

techniques such as :
ra

• E.g. : CCF, cirrhosis,

al

• Flame photometry.
aw

nephrotic syndrome.
r

• Indirect potentiometry.
ag
|
w
ro
ar

Renal loss : Non-renal loss.

M

1. Diuretics (M/c : Thiazides).

©

2. Adrenal insufficiency.
3. Tubular defects.
4. Cerebral salt wasting.

Classification of Hyponatremia :
Based on severity :

Severity S. Na+ (mEq/L)

Mild 130 - 134
Moderate 120 - 129
Severe 100 - 119
Very severe < 100

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 Posterior Pituitary Disorders 27

Based on duration : ----- Active space -----

Duration Causes Symptoms Management

1. Psychogenic • Mild - moderate : Headache,
polydipsia lethargy, confusion, fatigue 3% saline (100 mL) over 10 mins
Acute

< 48 hrs (Can be administered 3 times)

2. Post-op saline • Severe : Seizures, coning,
expansion herniation
↑S. Na+ by 4 - 6 mEq/L
Severe : Head injury/seizures

• Evaluate fluid status : NS

infusion if dehydrated
1. Head injury • Evaluate S. Na+
Chronic

2. SIADH
> 48 hrs/
3. All other Mild - moderate : Headache,
unknown > 120 mEq/L < 120 mEq/L
causes of lethargy, confusion, fatigue
hyponatremia

om
Conservative 3% saline

l.c
management infusion

ai
gm
(Rx of SIADH)
@
56
t4

Note :
chi
ra

Rapid correction of S. Na+ can lead to osmotic demyelination syndrome.

al
r aw

SIADH
ag

01:03:31
|
w

Causes of SIADH :
ro
ar
M

1. Paraneoplastic syndrome :
©

Small cell lung cancer (M/c) > Ca duodenum & pancreas.

2. Lung infections :
Necrotizing pneumonia, lung abscess.
3. Drugs :
• Cyclophosphamide.
• Clofibrate.
• Chlorpromazine.
• Chlorpropamide.
• Carbamazepine (Oxcarbamazepine > Carbamazepine).
• Vincristine.
4. CNS disorders :
Trauma, hemorrhage, infections, abscess.
5. Acute intermittent porphyria.

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 28 Medicine

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

Diagnostic Criteria :
1. ↓S. osmolality.
2. ↑Urine osmolality.
3. Euvolemia.
4. ↑Urine Na+ : > 40 mEq/L (D/t ↑natriuretic peptides).
5. Absence of pituitary/adrenal/thyroid/renal/liver disease.

Management of SIADH :
1. F luid restriction :
< 800 mL/day (Treatment of choice).
2. Urea/salt tablets :
↑Solute load.

om
3. Tolvaptan :

l.c
V2 receptor antagonist.

ai
gm
4. Furosemide : @
56
Blocks ADH action on the thick ascending limb ↑S. Na+.
t4
chi

SIADH vs. Cerebral Salt Wasting :

ra
al
aw

SIADH Cerebral salt wasting

r
ag

Causes Head injury Head injury (M/c : SAH)

|
w
ro

• ↑Brain natriuretic peptide

ar

• Impaired sympathetic drive

M
©

Inappropriate -
Pathogenesis RAAS
ADH secretion

Natriuresis.
Hyponatremia Euvolemic + Hypovolemic +
ECF volume ↑ ↓

BP & CVP N N /↓
Blood urea N /↓ ↑

Hematocrit N ↑

Plasma uric acid ↓ N /↓

Urinary Na+ ↑↑

Urine volume N /↓ ↑

BUN : Creatinine ↓ ↑

Treatment Fluid restriction Normal saline

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 Adrenal Cortex 29

ADRENAL CORTEX ----- Active space -----

Parts of adrenal gland :

Medulla (20%) Cortex (80%)

Anatomy of Cortex 00:00:20

Development :
Completed by 28-32 weeks (IUL).
Intermediate mesoderm
4-6 weeks IUL

om
Urogenital ridge (Coelomic epithelium)

l.c
ai
6-8 wks IUL

gm
Adrenogenital primordium 56
@
t4

Fetal adrenal cortex Bipotential gonads

chi

9 wks IUL
ra

SRY gene 9-12 wks IUL

al

Fetal adrenal gland

aw

Fetal testes Fetal Ovary

r
ag
|
w

Zones of Cortex :
ro
ar
M

Zona glomerulosa Zona fasciculata Zona reticularis

©

After birth : From After birth : From

Development By 2-3 y
outer DZ outer DZ
% of cortex 15% 75% 10%
DHEAS

Hormones Biochemical adrenarche/

Aldosterone Cortisol Clinical pubarche (6-8 y) :
released
1. Pubic & axillary hair
2. Apocrine body odour
Controlled by RAAS ACTH

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 30 Medicine

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

Adrenal gland layers

om
l.c
Synthesis of Hormones

ai
00:11:06

gm
Circulating LDL @ Cholesterol
56
t4
hi

StAR (Steroid acute

c
ra
al

regulatory protein)
raw
ag

• Rate limiting
|
w
ro

• Deficiency/Mutation :
ar
M

Congenital lipoid adrenal hyperplasia

©

Primary Hyperaldosteronism (PHA) 00:23:18

M/C cause of endocrine HTN.

Etiology :

Inherited : Acquired :
Familial Hyperaldosteronism : AD
(Type 1 : GRA) B/L Micronodular U/L adenoma
adrenal hyperplasia > (Conn’s
(60%) syndrome)

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 Adrenal Cortex 31

Pathophysiology & Presentation : ----- Active space -----

+ Basolateral membrane
ENaC
Na+ + H2O AIP +
K+ MR Aldosterone ↑↑ Aldosterone
(Exchanged for GRA : Glucocorticoid Remediable Aldosteronism
P-cell
H+ in I-cell) (Collecting duct) MR : MC receptor
Presentation : AIP : Aldosterone Induced Protein
• Hypertension : • Hypokalemia.
PHA seen in : • Alkalosis.
- 5% of overall HTN.
- 10% of HTN in young.

om
l.c
- 20% of resistant HTN.

ai
gm
Management :
@
56
Stop spironolactone
t4

Indications :
chi

Screening test • All newly diagnosed HTN

ra
al

• Young onset HTN

aw

• HTN + hypokalemia
r
ag

• PAC > 20 ng/dl PAC > 10 ng/dl • Target organ damage (Disproportionate to HTN) :
|

• PRA < 1 ng/ml/hr PRA < 1 ng/ml/hr - Microalbuminuria

w
ro

• Hypokalemia - LVH
ar

- Retinopathy
M

Confirmatory test :
©

Saline infusion test (2L of NS/4hr)

PAC > 10 ng/dl (Measure every 30 min × 4 times)

PHA confirmed MRA : MR antagonist

PAC : Plasma aldosterone concentration
CT Abdomen (IOC) PRA : Plasma renin activity

• U/L adenoma
• < 35 years age B/L hyperplasia
• Hypokalemia -
Adrenal Venous Sampling
+ (Tests lateralization index)
U/L Adrenalectomy - ve
+ ve
Adrenalectomy on MRA :
affected side • Steroidal : Spironolactone > Eplerenone
• Nonsteroidal : Finerenone
Medicine • World of Revision • v2.0 • Marrow • 2025
 32 Medicine

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

Presentation Conditions
Acquired Inherited ( ↓Renin)
Hypertension • Apparent MC excess (AR)
• Primary • GRA : FHA Type 1 (AD)
hyperaldosteronism (AD) • Liddle syndrome (AD) :
Hypokalemia Alkalosis • Cushing syndrome Gain of function mutation
of ENaC
Normotensive/Hypotension
• Bartter Syndrome
-
• Gitelman syndrome
Hypokalemia Alkalosis
Hypertension
Gordon’s syndrome
-
(AR ; ↓Renin)

om
Hyperkalemia Acidosis

l.c
ai
gm
Adrenal Insufficiency (AI) 56
@ 00:42:36
t4

AKA Addison’s disease.

hi
c
ra

Etiology :
al
aw

Acquired causes :
r
ag
|

1° AI 2° AI (M/C)
w
ro

• TB Abrupt steroid withdrawal :

ar

• Autoimmune adrenalitis (AA) ≥ 7.5 mg/d prednisolone for ≥ 3 w

M
©

- Isolated AA
- Polyglandular autoimmune
Etiology syndromes Type 1 & 2 : Anti Suppress hypothalamo-
21α-hydroxylase antibodies pituitary axis
• Histoplasmosis Abrupt withdrawal
• HIV AI
Defect in Cortex of gland ACTH production
• ↓Cortisol
• ↓Sex steroids
• ↓Aldosterone : • ↓ Cortisol
- Hyperkalemia • ↓ Sex steroids
Findings
- Salt craving • N Aldosterone
- Postural hypotension • ↓ ACTH
• ↑ ACTH :
Hyperpigmentation

Medicine • World of Revision • v2.0 • Marrow • 2025

 Adrenal Cortex 33

Inherited causes : ----- Active space -----

Defect Features
• AI
• Alacrima
Triple A syndrome ALADIN gene mutation
• Achalasia
• ± Autonomic dysfunction
Congenital adrenal DAX - 1 gene mutation
hypoplasia (XLD)
AI
• AI
X linked Very long chain fatty • In white matter :
adrenoleukodystrophy acids accumulation Regression of developmental
milestones

Presentation :

om
Symptoms : Signs :

l.c
• Eosinophilia.

ai
Symptoms Cause

gm
• Auricular calcification.
Hyperpigmentation ↑ACTH @
• Variable gland size.
56

• Hypotension
t4
hi

• Hypoglycemia
c
ra

• Weight loss ↓GC

al

• Asthenia
aw

• Euvolemic hyponatremia
r
ag

• Hyperkalemia
|
w

• Salt craving ↓MC

ro

•
ar

Hypovolemic hyponatremia
M

• Dry skin
©

↓Sex steroid
• Loss of libido

Ix :
8 am plasma cortisol (PC) + ACTH

• PC < 3 µg/dl PC : 3-20 µg/dl

• ACTH : 2x upper limit
Synacthen stimulation test :
1° AI confirmed. IM or IV 250 µg Cosyntropin
4 samples every 30 min
PC : < 18 µg/dl

AI confirmed.

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 34 Medicine

----- Active space ----- Rx :

• Oral hydrocortisone : 10 mg - 5 mg - 5 mg.
- Any stress : Double dose.
- Fever (>39°C).
- Diarrhea. Triple dose
- Vomiting.
• Oral fludrocortisone : 50 mcg (Max. : 200 mcg).

Addisonian Crisis :
Etiology :
• Abrupt withdrawal of steroids.
• Infections.

Presentation :

om
l.c
• Nausea & vomiting.

ai
gm
• Severe abdominal pain.
• Constipation. @
56
t4

• Depleted intravascular volume.

chi
ra

Rx :
al
aw

• IV fluid (DNS).
r
ag

• IV hydrocortisone.
|
w

• Fludrocortisone.
ro
ar
M

Cushing’s Syndrome
©

00:56:29

Pathophysiology :
Cortisol (GC + MC) 11β-OH steroid dehydrogenase type 2 Cortisone (GC)
Acquired deficiency
Cushing’s/Hypercortisolism :
• Hypertension
• Hypokalemia
• Alkalosis.

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 Adrenal Cortex 35

Classification & Etiology : ----- Active space -----

Exogenous cushings Endogenous cushings

90% 10%
ACTH dependent ACTH independent :
75% 15% • Adrenal adenoma
• Adrenal Ca (M/c cause in children)
Cushing’s disease : Paraneoplastic syndrome
• B/L hyperplasia
Pituitary microadenoma (D/t ACTH) : • McCune Albright Syndrome
(M/C cause in adults). • Small cell Ca of lung
(M/c cause in infants)
• Bronchial carcinoids
• Primary pigmented nodular
• Medullary Ca of thyroid.
adrenocortical disease (PPNAD) :
A/w Carney’s complex (MEON).

Pseudo cushing’s :

om
Hypercortisolism in chronic stress states :

l.c
ai
• Obesity. • Depression.
gm
• Alcoholism. @
56
t4

Presentation :
chi
ra
al

Symptoms Discriminatory value

aw
r

• Proximal myopathy
ag
|

• Facial plethora
w
ro

• Bruising & ecchymoses

ar

Protein catabolism ↑
M

• Violaceous striae
©

• ↓Bone mineral density :

Fracture & osteoporosis
Minimal lipolysis :
Body fat
• Buffalo hump ↓
redistribution
• Central obesity
↑Carbohydrate Diabetes mellitus ↑
• Hypertension
↑Mineralocorticoid • Hypokalemia ↑
• Alkalosis
• Acne
Sex steroids • Hirsutism -
• Menorrhagia
• Psychosis
CNS effect -
• Depression

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 36 Medicine

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

Midnight cortisol 8am plasma cortisol Overnight Dexamethasone

suppression test :
1 mg oral dexa given (11 pm)

Pseudocushing’s
Serum : < 1.8 µg/dl Serum : ≥ 1.8 µg/dl
Cortisol levels

Suspected
Salivary : < 5.5nmol/L Salivary : ≥ 5.5 nmol/L
at 8 am the
Cushing’s ruled out +ve ↓↓↓ Loss of diurnal next day
variation
< 1.8 µg/dl > 1.8 µg/dl
Exogenous Endogenous
Cushing’s Cushing’s -ve +ve

Any 2/3 in
Low dose dexamethasone test :

om
favour of
• 0.5mg QID X 2 days Cortisol level < 1.8 µg/dl : -ve

l.c
Cushing’s on 3rd
day
(8 doses)

ai
gm
• Indications : > 1.8 µg/dl : +ve
@
- PCOS phenotype
56
- Patient on : OCP, HRT
t4
c hi
ra

9am plasma ACTH

al
aw
r
ag

<10 pg/mL : 10-50 pg/mL : 50-100 pg/mL : > 100 pg/ml :

|

Adrenal cause Pituitary cause Pituitary + Adrenal cause

Paraneoplastic cause :
w
ro

• Hypokalemia,
ar

CT Abdomen Gd enhanced MRI brain : To detect mass

M

hypertension, alkalosis
©

• Hyperpigmentation
U/L adenoma > B/L hyperplasia ≥ 6 mm < 6 mm / - • ↓Protein catabolism
U/L B/L Inferior petrosal
adrenalectomy adrenalectomy sinus sampling :
Petrosal ACTH
Nelson’s Syndrome : Peripheral ACTH
-ve feedback lost
≥2 <2 PET scan
ACTH secreting tumor
(Pituitary macroadenoma) Trans sphenoidal surgery
Hyperpigmentation Mass effects Medical Rx : Prevent relapse
Ketoconazole
Metyrapone
Mifepristone
Pasireotide

Hyperpigmentation
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 Adrenal Medulla 37

ADRENAL MEDULLA ----- Active space -----

Physiology of Adrenal Medulla 00:00:05

Adrenal gland Cortex (80%).

Medulla (20%) Hormones Adrenaline (80%).
Noradrenaline (20%).

Structure :
Origin : Neural crest (45 day POG).
Composition :

om
Note :
Features Markers

l.c
• Markers of cortex : SF-1, inhibin.

ai
• Major cells
• Chromogranin

gm
Chromaffin cells • Eosinophilic • Adrenomedullin :
• Synaptophysin @
• Granules Hormones - Vasodilator.
56
t4

Sustentacular cells Supporting cells S-100 - Source : Endothelial cells.

chi
ra

Hormone synthesis (Pulsatile) :

al
aw

Tyrosine
r
ag

Tyrosine hydroxylase Rate limiting step

|

DOPA
w
ro

Dopa decarboxylase Metabolites formation (Continuous) :

ar
M

Dopamine Homovanillic acid (HVA).

©

Norepinephrine Normetanephrine
PNMT Vanillyl mandelic acid (VMA).
Epinephrine. Metanephrine

Phenylethanolamine-N-methyl transferase (PNMT) :

• Exclusive to adrenal medulla.
• Cortisol + PNMT expression.
• Von-Hippel lindau (VHL) Produce Hypoxia-inducible - PNMT expression
• Succinate dehydrogenase (SDH) B mutation
factors (HIF)
↑NE.
Pheochromocytoma 00:06:00

• Neural crest cell tumor.

• Arise from : Chromaffin cells ↑Catecholamines/their metabolites.
• Markers : Chromogranin, Synaptophysin.
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 38 Medicine

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

Familial (40%) : A/w
• MEN 2 : M/c
• VHL B/L (40%).
• SDH-B mutations
• NF-1 : U/L.

Malignant (50%) : SDH-B (M/c) ↑Risk of metastasis (Surest sign of malignancy).

Types :

Adrenal (75%) : Extra-adrenal/Paraganglioma (25%) :

Epinephrine > Norepinephrine (NE).

Sympathetic (20%) : Parasympathetic (5%) :

om
• Organ of Zuckerkandl (Adrenal) : M/c site. • Site : Carotid body > Jugular bulb.
• ↑NE (D/t - PNMT). • Non-functional.

l.c
ai
gm
Clinical Presentation : 56
@
Symptomatic (75%) : 6P1W
t4
hi

• Panic attack (M/c) : A/w 20% Normal BP.

c
ra

80% Paroxysmal hypertension 20%  Sustained

al
aw

Episodic headache (M/c) hypertension.

r
ag
|
w
ro

Triad
Perspiration Palpitations/
ar
M

Tachycardia
©

• Abdominal pain : D/t ↑S. Ca2+.

• Pallor : S/o malignancy.
• Postural hypotension : D/t intravascular volume.
• Weight loss : D/t continuous sympathetic activity (↑r/o DM).
Adrenal incidentaloma (25%).

Note :
• Other endocrine conditions with ↑Ca2+:
- Addisons. - Acromegaly.
- Thyrotoxicosis.
• Other EPO producing tumors :
- RCC (M/c paraneoplastic). - Hemangioblastoma.
- Meningioma. - Fibroid.
- Hepatoma.

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 Adrenal Medulla 39

Diagnosis : ----- Active space -----

Screening test : 24 hr urine fractionated metanephrine/nor-metanephrine (98% sensitive & specific)

+ve -ve

MRI abdomen (Imaging IOC)

Clinical suspicion + Rules out
Lesion not seen pheochromocytoma
• Gallium DOTATATE PET scan (IOC for extra adrenal).
Plasma fractionated metanephrines
• FDG PET.
(100% sensitive).
• MIBG.
Management :
Preoperative : Admit 7-10 days prior to Sx.
Days before Sx Aim Rx
Replenish fluids Iv fluid therapy

om
l.c
• α-blocker (Non-selective) : ± • Calcium channel blockers :

ai
7-10 Phenoxybenzamine (DOC) - Amlodipine - Nicardipine

gm
Control BP (HTN)
unavailable 56
@ - Nifedipine - Verapamil
Prazosin
t4

2-3 Control HR β-blocker : Atenolol

chi
ra
al

Intraoperative :
r aw

Hypertensive crisis :
ag
|

• Sodium nitroprusside. • Iv phentolamine.

w
ro

• Nicardipine.
ar
M
©

Multiple Endocrine Neoplasia (MEN) Syndromes 00:19:00

Types Genetic association Manifestations

• Young age
• M=F
• Major endocrine :
- Parathyroid (90-100%)
- Enteropancreatic neuroendocrine tumor (50-70% ) : M/c/c of death
MEN 1/ - Pituitary (30-50%)
• Menin protein : Chr 11q • Minor endocrine :
Wermer
• AD inheritance - Adrenal adenomas (20%)
syndrome - Thymic neuroendocrine tumors (5%) : 2nd M/c/c of death
• Skin :
- Angiofibroma (M/c)
- Collagenoma
- Lipoma
• Others : Meningioma

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 40 Medicine

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

Types Genetic association Manifestations

• Classical :
- Medullary thyroid cancer (90-100%)
- Pheochromocytoma (50%)
RET proto oncogene : - Parathyroid hyperplasia (25%)
MEN 2A
Chr 10q • Associations :
- Cutaneous lichen amyloidosis
MTC + Pheochromocytoma ± PTH
- Hirschsprung disease
- Familial medullary thyroid cancer (FMTC)
MTC + Pheochromocytoma + 3M ± Megacolon
MEN 2B/ • Marfanoid habitus
-
MEN 3 • Mucosal & intestinal ganglioneuromatosis
• Medullated corneal nerve fibres
• Parathyroid • Testicular/Ovarian tumor
MEN 4 CDKN1B gene

om
• Pituitary • Renal tumors

l.c
ai
Major Endocrine Manifestations of MEN 1 :

gm
@
56
Parathyroid : Enteropancreatic neuroendocrine tumors : Pituitary :
t4

1o Hyperparathyroidism (M/c) : • Pancreatic polypeptide secreting tumor (PPoma) : M/c. Prolactinoma (M/c)
chi

• C/f : - Non functional.

ra
al

- ↓↓↓Bone mineral density - Risk of malignant conversion.

aw

- Mild ↑S. Ca²+ • Gastrinoma (2nd M/c) :

r
ag

• Rx : 3½ gland parathyroidectomy. - Small. - Multifocal.

|

- B/L. - Dx: EUS.

w
ro

• Insulinoma
ar

• Glucagonoma :
M

- Weight loss - Migratory necrolytic

©

- Diabetes erythematous rash

• VIPoma :
- Watery diarrhoea - Hypokalemic normal
- Hypochlorhydria anion gap metabolic
acidosis (NAGMA)
Note :
MEN 1 associated Overall
M/c/c Asymmetric 4 gland hyperplasia Adenoma
1° hyperparathyroidism Age group Young Elderly
Predominant in M=F F>M
M/c site Duodenum Passaro’s triangle
Gastrinoma
Malignant potential Less More
M/c site Head = Body = Tail Head
Insulinoma
Malignant potential ↑↑ 10%
Aggressiveness ↑ ↓
Prolactinoma
Adenoma Macro Micro
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 Adrenal Medulla 41

Multiple Endocrine & Other Organ Neoplasia Syndromes 00:28:40 ----- Active space -----

Manifestations
Mutation/defect
Endocrine Neoplasia
Hyperparathyroidism Parafibromin/
Parathyroid carcinoma Jaw tumor
jaw tumor syndrome CDC 73
• Pituitary adenoma
Protein kinase
• GH secreting adenoma
Carney complex A regulatory 1 α Atrial myxoma
• PPNAD : Primary pigmented nodular
(PRKAR1α)
adrenal disease (A/w cushing’s syndrome)
Von Hippel-Lindau
pVHL Pheochromocytoma Cerebellar hemangioblastoma
(VHL)
Neurofibromatosis
Neurofibromin Neurofibromas with pheochromocytoma Optic nerve sheath tumors
type 1 (NF-1)
• Multiple hamartomatous GI

om
Cowden’s syndrome PTEN Autoimmune hypothyroidism polyps

l.c
• Breast Ca

ai
gm
McCune-Albright Post zygotic • Precocious puberty • Prolactinoma
@ Polyostotic fibrous dysplasia
syndrome (Acquired) somatic mutation • GH adenoma • Cushing’s
56
t4
chi

Autoimmune Polyendocrine Syndromes (APS)

ra

00:31:33
al
aw

AKA polyendocrine autoimmune syndromes.

r
ag
|
w

APS-1/APECED APS-11
ro
ar

Inheritance AR Polygenic
M

Gene/HLA association AIRE gene mutation HLA DR3 & DR4

©

Gender M=F F>M

Age of onset Childhood Adult
1° hypoparathyroidism Major manifestation -
M/c thyroid manifestation Graves disease Hashimoto’s
Addison’s disease + M/c
C/f Type 1 DM + +
Hypogonadism + +
Mucocutaneous candidiasis + -
Nail & skin changes + -
Antibody Anti 21-OH antibody

APECED : Autosomal polyendocrinopathy with candidiasis & ectodermal dystrophy.

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 42

----- Active space ----- DIABETES MELLITUS

Diabetes defining infections :

• Rhinocerebral mucormycosis. • Emphysematous pyelonephritis.
• Malignant otitis externa. • Emphysematous cholecystitis.

Acute Complications: DKA & HHS 00:00:42

Diabetic ketoacidosis (DKA) :

Primarily seen in Type 1 DM.
Precipitating factors :

om
• Infection : Pyelonephritis (M/c). • Non-compliance.

l.c
• Infarction. • Pregnancy.

ai
gm
Pathophysiology : @
56
t4
chi
ra

Absolute insulin deficiency ↑ Counter regulatory hormones

al
aw

↑Carnitine +
r

↑ Proteolysis
ag

↑ HSL palmitoyltransferase
|

(In mitochondria)
w

↑ FFA ↑ Amino acids

ro
ar
M

Promotes FFA uptake ↑ Gluconeogenesis

©

gluconeogenesis β-oxidation
Acetyl CoA Hyperglycemia

Acetoacetate Osmotic diuresis

(Loss of H2O & electrolyte)
β-hydroxybutyrate Acetone
Dehydration
(Volume deficit : 6 - 9 L).

Clinical features :
• Symptoms : • Signs :
- Recurrent vomiting. - Tachycardia.
- Dyspnea (X-ray : Shows clear - Dehydration.
lung fields). - Tachypnea.
- Abdominal pain. - Abdominal tenderness.

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 Diabetes Mellitus 43

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

• Aggressive 2 IV lines

IV Fluid : Regular insulin

(M/c complication in children :
3L 3L 3L Cerebral edema) :
(1-3 hrs) (6-9 hrs) (12 hrs)
+
0.1 U/kg : Bolus
KCl (1 ampoule) in every 1 L of NS.
0.1 U/kg/hr : Infusion

Taper the dose & overlap

with S/C insulin

om
l.c
Hyperosmolar Hyperglycemic Syndrome (HHS) :

ai
gm
Risk factors :
@
• Elderly patient.
56
t4

• Type 2 DM.
chi
ra

• LRTI (Over a week).

al
aw

• Uncontrolled hyperglycemia.
r
ag

Pathophysiology :
|

Relative insulin deficiency

w
ro
ar

±↑Counterregulatory hormones
M
©

↓ Peripheral utilization of glucose

Hyperglycemia
Prolonged : ↑Severity
Osmotic diuresis

Dehydration (Volume deficit : 9 - 12 L)

↑Osmolarity.
Management :
↑Mortality if delayed
• Same as DKA.
• Exceptions :
- No correction of KCl required.
- Slower fluid correction.
- If hypernatremia + add ½ NS.

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 44 Medicine

----- Active space ----- DKA vs. HHS :

DKA HHS
Glucose (mg/dL) 250 - 600 600 - 1200
Na+ (mEq/L) 125 - 135 135 - 145
K+, Mg2+, Cl-, PO4 3- N N
Creatinine ↑ ↑↑
Osmolality (mOsm/L) 300 - 320 330 - 380
Plasma ketones +++ +/-
S. Bicarbonate (mEq/L) < 15 N /↓
Arterial pH 6.8 - 7.3 > 7.3
Arterial pCO2 (mmHg) 20 - 30 N
Anion gap ↑ N /↑

om
Management of Diabetes Mellitus 00:08:58

l.c
ai
gm
Drugs with Macrovascular Benefit :
@
56
Cardiovascular & renal benefits.
t4
hi

SGLT-2 inhibitors :
c
ra
al

• Dapagliflozin, Empagliflozin.
aw

• Advantages :
r
ag

- Natriuresis, diuresis without tachycardia.

|
w
ro

- Glycosuria.
ar
M

- Weight loss.
©

- Cardiac & renal benefits.

- Used in metabolism associated steatohepatitis.
• S/e :
- Recurrent UTI.
- Fungal infection.
- Euglycemic ketosis.

GLP-1 analogues :
• Semaglutide (Oral, S/C), Tirzepatide (GLP-1 & GIP-dual agonist).
• Advantage : Max. weight loss.

Drugs with HbA1C Lowering Potential :

Maintain optimal blood glucose levels.

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 Diabetes Mellitus 45

Metformin : ----- Active space -----

• 1.5 - 2% HbA1C lowering potential.
• Weight neutral.
• ↓Hypoglycemia risk.
• C/i : GFR < 30 mL/min.

Other Drugs (↓Usage) :

DPP-4 inhibitors :
• Cardiac neutral.
• Advantages :
- No hypoglycemia.
- No weight gain.

om
Sulfonylureas : Gliclazide.

l.c
ai
Additional Measures :
gm
@
56
t4
hi

BP < 130/80 mmHg LDL < 100 mg/dL :

c
ra

• If additional risk factor + : < 70 mg/dL.

al
aw

CCB + ARB. • If ASCVD + : < 55 mg/dL

r
ag
|

Rosuvastatin 20 mg.
w
ro
ar
M
©

If Age > 40 yrs + ≥ 1 risk factor : Aspirin.

Additional Ix :
• Fibroscan.
• Retinal evaluation.
• Proteinuria evaluation.

Insulin Therapy :
Indication :
• HbA1C > 9.5
• DM other than type 2 Detected for first time.
• Micro/macrovascular complications

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 46 Medicine

----- Active space ----- Classification of Diabetes 00:16:00

Features
• Immune mediated B cells destruction T cells : Insulitis
B cells : Anti GAD antibodies
• B cells :
Type 1
- > 70% destruction : Symptoms begin
- 30% functioning Honeymoon period Complete destruction
• HLA association +
Insulin Glucotoxicity + Pancreatic
Type 2
resistance Lipotoxicity destruction
Type KPD Type 2 with features of Type 1
1.5 LADA Type 1 with features of Type 2
Type 3/3A
↓ IDE ↑ Aβ amyloid Aβ 42 Neuritic plaques &

om
(Alzheimer’s
(APP gene : Chr. 21) Neurofibrillary tangles
disease)

l.c
ai
• Fibrocalculous chronic calcific pancreatitis :

gm
- Young male @
56
- Acute on chronic pancreatitis
Hybrid forms

t4

Type 3C - Large duct dilatation (with stones)

chi

(Pancreatic) - Fibrosed pancreas

ra
al

• IgG4 related disease

aw

• Cystic fibrosis
r
ag

• Hemochromatosis
|

Type 3D • L-asparaginase • Nicotinic acid

w
ro

(Drug induced) • Tacrolimus • Olanzapine

ar
M

Type 4 Type 2 + ↑ T-regulatory cells ↑Tolerance ↓ Complications

©

(MARD) functions
MODY Suboptimal response to insulin
GDM -
• KPD : ketosis prone DM.
• LADA : Latent autoimmune DM in adults.
• IDE : Insulin degrading enzyme.
• MARD : Mild age related DM.
• MODY : Maturity onset DM in young.

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 Diabetes Mellitus 47

Type 2 DM 00:21:40 ----- Active space -----

Etiopathogenesis :
GIT

Renal Adipose Tissue

Impaired
incretin α receptor
effect Abdominal
↑SGLT-2 obesity/ diabesity
β receptors
↑Na+- Glucose + ↑HSL
absorption Lipolysis

Brain FFA
Liver
Portal
circulation

om
Glucotoxicity (↑ FFA)

l.c
Ominous D/t - CPT

ai
Neurotransmitter

gm
dysfunction octet of expression
DeFronzo @ on
56
mitochondria
t4

↑ Fatty acyl CoA

chi
ra

scle
al

l mu
aw

Deposition
Sk eleta
r
ag

↑ Glucagon Pancreas ↑ Resistance

|

(Counter
w
ro

regulation ↓ Glucose uptake

ar

hormone)
M

Gluco + lipotoxicity (GLUT-4)

©

Pancreatic
destruction

Faithless 14 :
Treacherous 13 :
Dirty dozen :
• ↓Vit. D
Ominous octet +
• ↓Dopamine Serotonin : Iron in b cell :
+ +
• Hypogonadism ↑HSL ↑Toxicity
• RAS activation

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 48 Medicine

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

Natural History of Type 2 DM :

om
l.c
Diagnosis 00:26:34

ai
gm
Dx of Diabetes : @
56
t4
chi

Fasting : PPBS : HbA1C : RBS : Continuous blood

ra
al

≥ 126 mg/dL. ≥ 200 mg/dL. ≥ 6.5%. ≥ 200 mg/dL glucose monitoring

raw

+ symptoms. (Time in target) :

ag

≥ 70% (Specific).
|
w

Factors Affecting HbA1C:

ro
ar
M
©

False ↑: False ↓: ↑/↓ :

• Iron deficiency anemia. Hemolytic anemia. β thalassemia.
• Renal failure.
• Hypertriglyceridemia.

Dx of Prediabetes :

Fasting : PPBS : HbA1C :

100 - 125 mg/dL. 140 - 199 mg/dL. 5.7 - 6.4%.

• > 18 yrs & ↑body wt (Obese habitus).

• Rx :
- Metformin
- PPAR-γ (Pioglitazone) Adv : Prediabetes Delayed Diabetes.
Disadv : #, salt & H2O retention, bladder cancer.
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 Diabetes Mellitus 49

Approach :
Fasting C-peptide ----- Active space -----

( N : 0.3 - 0.6 nmol/L)

Decreased N

Ab +ve Ab +ve Ab -ve

Type 1. LADA. Complications :

• Resistance
• Micro/Macrovascular

+ -

om
Type II MODY

l.c
ai
gm
(Family history + )
@
56
C-peptide
t4

↑ ↓
c hi
ra

Blood ↑ Type 2 DM Type 1 DM

al
aw

glucose ↓ Insulinoma Exogenous insulin

r
ag
|

Autoimmune Markers in Type 1 DM :

w
ro
ar

• Islet cell antibodies : Earliest.

M

• Glutamic acid decarboxylase (GAD65) : Most specific & sensitive.

©

• Anti insulin auto antibodies (IAA) : Not detected in patients on insulin Rx.
• Zn transporter 8 (ZnT8).

LADA, KPD and MODY 00:34:20

LADA vs. KPD :

LADA KPD
Age Young adult
Gender M=F M>F
Presentation Insidious Explosive
Body weight Lean Obese
Ketosis - + (At onset)
Antibodies +++ +
Initial OHA Insulin
Rx
Long-term Insulin OHA

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 50 Medicine

----- Active space ----- MODY :

• AD.
• Family history + : ≥ 3 successive generations.

Features :
• Onset : 25 yrs of age.
• suboptimal response to glucose (No resistance).
• No macro/microvascular complications.
• No ketosis.

Rx : Low dose sulfonylureas.

Types :

om
Type 1 : Type 2 : Type 3 (M/c) : Type 4 : Type 5 :

l.c
HNF4α defect. • Glucokinase defect. HNF1α defect. Insulin promoter • HNF1β defect.

ai
gm
• Present at birth. factor-1 defect. • A/w :
@ - Renal cysts.
56
- Genital anomalies.
t4
c hi
ra
al

Type 1 vs. Type 2 DM

aw

00:36:34
r
ag
|
w
ro

Type 1 Type 2
ar

Age group Younger Older

M
©

Body weight (Fat : muscle ratio) Thinner Obese

Family history - +
Osmotic symptoms + Variable
DKA + Rare
C-peptide ↓ ↑
Markers of insulin resistance :
• Acanthosis nigricans
• Balanoposthitis - +
• Hirsutism
• PCOS
Dyslipidemia - +
Hyperuricemia - +
Antibodies + -

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 Diabetes Mellitus 51

Metabolic Syndrome 00:37:25 ----- Active space -----

Adult Rx Panel III Definition :

Criteria :
1. Waist circumference M : 102 cm
F : 88 cm
2. TG > 150 mg/dL
3. HDL M : < 40 mg/dL Any 3 positive.
F : < 50 mg/dL
4. BP : 130/85 mm Hg
5. FBG : > 100 mg/dL

Note :
Diabesity/adiposopathy : Diabetes + Obesity.

om
l.c
Prenatal Factors :

ai
gm
↑Maternal age/other risk factors Uteroplacental insufficiency
56
@
Predisposition to metabolic syndrome.
t4
chi

Effect of Incretins
ra

00:40:02
al
aw

Physiology :
r
ag

Intravenous
insulin
|

Oral glucose meal

w

Intrajejunal
ro

insulin
Insulin
ar

Release of incretin spike

M

after oral
©

(GIT) glucose

Augments release
of insulin.

Effect of incretin hormones

Features :
Incretin : GLP-1 > GIP Rapidly degraded by DPP-4.
(L cells of ileum & colon) (K cells of jejunum)
GLP-1 :
• Advantages : • Recombinant GLP-1 : Semaglutide.
- Inhibits glucagon. • Dual GLP-1 & GIP action : Tirzepatide.
- Delays gastric emptying.
- Promotes satiety weight loss.
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 52

----- Active space ----- CALCIUM METABOLISM AND THYROID

DISORDERS

Calcium 00:00:40

Body stores : 1000 - 1300 g.

Bones : 99.3%. Soft tissue : 0.6%. ECF : 0.1%.

48% : Free form.

Calcium in blood 40% : Bound to albumin Ca2+ adjusted for albumin.

om
10% : Bound to other proteins.

l.c
ai
Corrected calcium :
gm
@
• Serum calcium (S. Ca2+) + 0.8 x (4 - S. albumin).
56

• Range : 8.6 - 10.3 mg/dL.

t4
chi
ra

Metabolism :
al
aw

Absorption : Jejunum (20% dietary Ca2+)

r
ag
|
w
ro

Active (95%) : Passive (5%) :

ar
M

Regulated by Vitamin D Not regulated

©

(Calcitriol).
Ca2+ intake : Milk alkali syndrome :
>4g/day • Hypercalcemia.
• Calciuria.
• Nephrocalcinosis.
Renal handling :
Reabsorption Excretion :
<4 mg/kg/day.
PTH independent (65%) : PTH dependent
PCT via paracellular pathway.

15% : 10% :
Thick ascending limb (TAL) DCT (Active).
via paracellular pathway.
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 Calcium Metabolism and Thyroid Disorders 53

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

↑Risk of stone formation :
Risk factors Excretion
Hypercalciuria > 4 mg/kg/day
Hyperuricosuria > 7 mg/kg/day
Hypocitraturia < 11 mg/kg/day
Regulation :
↑Ionised calcium

Immediate response Delayed response

+ +
CaSR in parathyroid gland CaSR in TAL

om
- -

l.c
PTH secretion. Reabsorption

ai
gm
+
@
Excretion (Hypercalciuria).
56
t4
hi

CaSR mutation :
c
ra
al
aw

Loss of function : Gain of function :

r
ag

Familial hypocalciuric hypercalcemia (AD) : Bartter syndrome type 5 (AD) :

|
w
ro

↓Excretion. ↑Excretion Hypocalcemia.

ar
M

Hypercalcemia
©

00:07:26

≥ 10.4 mg/dL corrected Ca2+.

Presentation :
• Painful bones. • Fatigue overtones.
• Renal stones. • Psychiatric moans.
• Abdominal groans.

Etiology :

Thiazides. Endocrine : Osteolytic :

• Pheochromocytoma. • Multiple myeloma.
• Acromegaly. • Breast cancer.
• Thyrotoxicosis.
• Addison’s disease.
Medicine • World of Revision • v2.0 • Marrow • 2025
 54 Medicine

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

ECG : Short QT interval.
X-ray :

Subperiosteal resorption Rugger jersey spine Short QT interval

(2° > 1° hyperPTH)

om
l.c
iPTH levels :

ai
• Tested by IRMA (Immunoradiometric assay)

gm
• PTH t½ : 2 - 4 mins @
56
• N : 50 - 100 pg/mL
t4
chi
ra

< 50 pg/mL : > 50 pg/mL

al
aw

PTH independent hypercalcemia

r
ag

PTH dependent hypercalcemia :

|

< 20 pg/mL : 20-50 pg/mL

w

• 1° hyper PTH ↓S.PO43- :

ro

Squamous cell Ca - U/L adenoma : Elderly female

ar

(↑PTHrP) Vitamin D levels

M

- Hyperplasia : MEN syndrome

©

- Carcinoma :
PET scan. Hyperparathyroidism, Jaw tumor syndrome
• Lithium
Conditions 25-OH-D3 1,25-(OH)2-D3 • FHH
Hypervitaminosis D ↑ ↑ • 3° hyper PTH : Long standing 2° hyper PTH (CKD)
Tumor producing
1-α-hydroxylase ↑Ca2+ & ↑PO43- ↑PTH
N ↑
(Sarcoid/lymphoma/
acromegaly) Tc Sestamibi scan

Adenoma excision :
Indications :
• Age < 50 yrs
• ↓bone mineral density
• ↑creatinine
• ↑24hr urine Ca2+ excretion
• Symptomatic

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 Calcium Metabolism and Thyroid Disorders 55

Hypercalcemic Crisis : ----- Active space -----

Rx :
• Fluids.
• Calcitonin.
• Bisphosphonates : Zoledronate (4 g).

Hypocalcemia 00:17:43

• < 8.6 mg/dL corrected Ca2+.

• M/c : Mg2+ deficiency.

Presentation :

Acute hypocalcemia : Chronic hypocalcemia :

om
• Neuromuscular irritability : • Basal ganglia calcification.

l.c
- Circumoral • Benign intracranial hypertension.

ai
gm
paresthesia. • Cataract.
56
@
- Tingling, numbness.
t4
hi

- Twitching.
c
ra

• Latent tetany
al
aw

- Chvostek sign.
r
ag

- Trousseau sign.
|
w

• Seizures.
ro
ar

• ECG : ↑QT interval.

M
©

Basal ganglia calcification

Hypoparathyroidism :

PTH S. PO43- S. Ca2+ Etiology

• Post surgery
True hypoPTH ↓ ↑ ↓ • DiGeorge syndrome
• APS-1
Acute stress :
• Sepsis
• Pancreatitis
Secondary hypoPTH ↑/N ↑ ↓
• Tumor lysis syndrome
• Hemolysis
• Rhabdomyolysis
Genetic defect :
PseudohypoPTH (PHP) ↑↑ ↑ ↓ • GNAS gene
• Gsα subunit defect

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 56 Medicine

----- Active space ----- PTH S. PO43- S. Ca2+ AHO Resistance

1A +
Complete

PHP
1B ↑ ↑ ↓ -
2 - Partial (↑U. cAMP)
PPHP N N N + -

Albright hereditary osteodystrophy (AHO) :

• Short 4th metacarpal/metatarsal.
• Short stature.
• Round facies.
• Mental retardation.

om
l.c
ai
gm
@
56
D D KK
t4
chi
ra
al

Short 4th metacarpal Knuckle-knuckle

aw

dimple-dimple sign
r
ag

APS-1 : Autoimmune polyendocrine syndrome type 1

|

PPHP : Pseudopseudohypoparathyroidism
w
ro
ar
M
©

Phosphorous 00:22:57

Hyperphosphatemia

PO43- containing enemas. ↑Release from cells ↓Excretion :

(Stress). Renal failure (CKD).

Hypophosphatemia

↑Uptake in cells : ↑Excretion :

Insulin administration in DKA. FGF-23 producing tumors.

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 Calcium Metabolism and Thyroid Disorders 57

Thyroid Hormone Synthesis 00:24:32 ----- Active space -----

Congenital hypothyroidism :

Dysgenesis (85%) : Dyshormonogenesis (15%) :

Defect in transcription factors. • Defect in enzymes of hormone synthesis.
• Goitre + .
Hormone Synthesis Steps :
1. Na+- I- symporter (Basolateral membrane) : Note :
• Used in thyroid scintigraphy : • I123 : Uptake.
- I123 Uptake N : 10 - 15%. • I124 : PET.
↑ : Graves disease. • I127 : Normal.
↓/nil : Cold nodule. • I131 : Radiotherapy.

om
- Tc . 99

l.c
• - by : Thiocyanates and perchlorate.

ai
gm
2. I- - Cl- antiport (Pendrin) : @
56

• Crossing of basolateral membrane.

t4
hi

• Pendred syndrome (SNHL + goitre).

c
ra
al

3. Organification (I- I2 ) :
r aw

Mediated by :
ag
|

• Dual oxidase 2 (DUOX2).

w
ro

• Thyroid peroxidase (TPO).

ar
M

4. Iodination :
©

Thyroglobulin (Enzyme
+ Tyrosine residue independent) MIT, DIT.
+ I2
5. Coupling :
• MIT + DIT TPO T3 (20%).
• DIT + DIT TPO T4 (80%).
6. Endocytosis.
7. Proteolysis and release : - by iodides (Wolff-Chaikoff effect)

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 58 Medicine

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

Peripheral Conversion :
T4 Reverse T3.
Deiodinase-3 3x potent than T4.
T3 (80%) ↑ Free form.
Deiodinase-2 (DI2)
Binds to nuclear receptors.
-
• Amiodarone • PTU
• Steroid • β blockers

Sick Euthyroid Syndrome/Low T3 Syndrome :

• Systemic illness
- • ↓↓T3 • ↓TSH
• Fever (ICU admitted) DI-2
• ↑T4 • ↑rT3
• Prolonged fasting

om
Hormones Bound To :

l.c
• Thyroid binding globulin (60 - 70%).

ai
gm
• Albumin. 56
@
• Transthyretin.
t4
chi

Thyroid Disorders
ra

00:35:04
al
aw

Hyperthyroxinemia :
r
ag

↑T3 & ↑T4

|
w
ro

↑FT3 & ↑FT4 N FT3 & N FT4 :

ar
M

D/t ↑TBG seen in :

©

Thyrotoxicosis d/t : Resistance to • Pregnancy

thyroid hormone : • OCP
↑ TSH • Chronic active hepatitis
Gland overactivity : ↑Store hormone • Tamoxifen
Hyperthyroidism release :
Subacute thyroiditis. Euthyroid hyperthyroxinemia.

1° : 2° :
• Autoimmune (Graves) : D/t TSH secreting
- Anti TSH Ab. adenoma.
- Anti Tg Ab.
- Anti TPO Ab.
• D/t toxic adenoma/MNG.

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 Calcium Metabolism and Thyroid Disorders 59

Evaluation based on TSH, FT3 & FT4 : ----- Active space -----

↑↑ TSH Normal TSH ↓ TSH (< 0.5 mIU/L)

Hypothyroidism (Autoimmune) : 2˚hypothyroidism 1. Symptomatic :
FT3 & FT4 Hashimoto’s thyroiditis d/t hypopituitarism Hypopituitarism
↓↓ (A/w autoimmune polyendocrine (Inappropriately 2. Asymptomatic :
syndrome) normal TSH ) Sick euthyroid
Subclinical hypothyroidism :
FT3 & FT4 If TSH > 10
Rx - -
Normal +
Ab/symptoms +
• TSH secreting adenoma
FT3 & FT4
• Resistance to thyroid - Thyrotoxicosis
↑↑
hormone (RTH) : No symptoms

om
Clinical Presentation of Thyroid Disorders 00:42:10

l.c
ai
Hypothyroidism :
gm
• Profound slowness : ↓BMR. @
• ↓ Catecholamine sensitivity.
56
t4

• ↑ BP : • Proteolysis ↓BMD ↑Fracture

chi

- D/t ↑peripheral resistance. incidence.

ra
al

- Despite ↓CO. • Hypothermia (Myxedema coma).

r aw

• Hypercholesterolemia : ↓Clearance.
ag
|
w

Hashimoto’s (Autoimmune) :
ro
ar

• TPO Ab (M/c)
M

Ab
©

• Thyroglobulin Ab
• TSH receptor Ab
• ↑ TSH
• ↑Matrix GAGs (Traps water) Puffiness.

Hyperthyroidism :

Graves : Subacute/de Quervain’s/

• Toxicosis symptoms : granulomatous thyroiditis :
- Restless, irritable. • Toxicosis features.
- ↑ HR, AF. • Postviral symptoms.
• D/t TSH receptor antibody : • Neck pain/tenderness.
- Ophthalmopathy. • ↑ESR.
- Dermopathy.
- Acropachy.
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 60 Medicine

----- Active space ----- HEART FAILURE AND CARDIOMYOPATHIES

Heart Failure 00:00:10

Structural/functional impairment of ventricles to pump out/fill blood.

Types :

Types Ejection fraction (EF)

HFpEF : HF with preserved EF > 50%
HFmEF : HF with midrange EF 40 - 50%
HFrEF : HF with reduced EF < 40%

om
l.c
ai
gm
HFpEF :
@
• Co-morbidity driven microvascular inflammation.
56

• Mortality : HFpEF > HFrEF.

t4
hi

• No guidelines for Mx (SGLT-2 inhibitors used).

c
ra
al
aw

NYHA Classification :
r
ag

Based on symptoms : Angina, dyspnea & palpitation (No syncope).

|
w
ro
ar

ClasseS Symptoms + Causes of mortality

M
©

I On exertion -
II On ordinary activities Sudden cardiac
III On less than ordinary activities death
IV At rest Pump failure

Stages of HF :

Stage Features
A Only risk factors (DM, HTN)
B A + structural damage (LVH)
C B + symptoms (M/c in hospitals)
D Refractory HF

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 Heart Failure and Cardiomyopathies 61

Presentation 00:07:50 ----- Active space -----

LV failure RV failure (↑RVEDP) :

• Impending RV failure :
Forward symptoms Backward symptoms ↑Abdomino-jugular reflex.
(↓CO/LV systolic failure) : (LVH/impaired relaxation) : • ↑RAP ↑SVC/IVC pressure :
• Cachexia (D/t ↑TNFα). ↑LVEDP - ↑JVP.
• ↓Urine output. - Hepatomegaly.
• Altered mentation. ↑LAP - Ascites.
• Cyanosis & cool extremities. - Edema.
• Narrow pulse pressure. ↑PCWP
• Pulsus alternans.
• Dyspnea.

om
• Cardiomegaly.

l.c
• S3 (D/t ↑ESV). • Paroxysmal nocturnal dyspnea (PND).

ai
gm
• Orthopnea.
@
• Acute pulmonary edema (Crepitations).
56
t4
chi
ra

Dyspnea :
al
raw
ag

Trepopnea : Bendopnea : Platypnea :

|

• On lying laterally. • On bending > 30 sec. Seen in

w
ro

• Prefer to lie on side of • Sign of advanced Hepatopulmonary

ar
M

effusion (HF : R > L ). heart failure. syndrome.

©

Note :
Precipitating factors
HFrEF/HFpEF Acute decompensated heart failure
(Rx : Diuretics).

Framingham Diagnostic Criteria :

Major criteria : Minor criteria :

• Acute pulmonary edema. • Hepatomegaly.
• Cardiomegaly. • Edema.
• HepatoJugular reflex. • Dyspnea on exertion.
• Neck vein distension. • Nocturnal cough.
• PND/orthopnea. • Pleural effusion.
• Rales. • Tachycardia.
• S3 gallop.
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 62 Medicine

----- Active space ----- Causes & Response Mechanisms 00:20:20

Causes of HFrEF :
• Ischemic cardiomyopathy : Post MI. • Cyanotic heart disease (Childhood).
• Dilated cardiomyopathy : Genetic. • Stressor factors :
• Valvular heart disease : - Anemia.
- AS. - Beri-beri.
- MR. - High output cardiac states.
- AR. - Thyrotoxicosis.

Response Mechanisms :
Neurohormonal mechanisms : Cardiac remodelling To preserve CO.
Mechanisms Features

om
• ↑Force of contraction ↑CO
Sympathetic system

l.c
• S/e : Tachycardia, ↑arrhythmogenesis

ai
gm
Vasoconstriction ↑Afterload
@
Angiotensin II
56
RAAS system ↑Aldosterone/ADH ↑Preload and
t4
hi

(↑Water retention) hyponatremia

c
ra

• ↑Na+ excretion
al
aw

Natriuretic peptides
• - Sympathetic/RAAS system
r
ag
|

Treatment
w

00:26:10
ro
ar
M

Fantastic 4 Drugs :
©

Drugs Significance
ARNI Sacubitril (Neprilysin inhibitor) + • ↓40% mortality
(Angiotensin receptor - neprilysin inhibitor) Valsartan (Angiotensin receptor blocker) • ARNI > ACEi > ARB
• Metoprolol
β blockers • Bisoprolol ↓30% mortality
• Carvedilol
• Spironolactone
MRA ARNI + Finerenone :
• Eplerenone
(Mineralocorticoid receptor antagonists) ↑ risk of hyperkalemia
• Finerenone (Non-steroidal)
• Dapagliflozin ↑Natriuresis/diuresis
SGLT-2 inhibitor
• Empagliflozin without tachycardia

Refractory Heart Failure :

Ivabradine (HR > 70 bpm + • LV assist devices
Transplant.
β blocker max. dose) • Cardiac resynchronization therapy
(Wide QRS)
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 Heart Failure and Cardiomyopathies 63

Cardiomyopathies 00:33:50 ----- Active space -----

• Structurally and functionally abnormal myocardium.

• Absence of HTN/CAD/congenital heart disease/valvular heart disease.

Classification :

Major : Minor :
• Dilated cardiomyopathy (DCM). • Takotsubo cardiomyopathy.
• Hypertrophic cardiomyopathy (HCM). • Arrhythmogenic right ventricular dysplasia (ARVD) :
• Restrictive cardiomyopathy (RCM). - AR. - Desmosomal protein defect.
• LV non compaction :
- XLR. - Tafazzin gene mutation.
• Tachycardia induced cardiomyopathy :

om
Longstanding A. fib.

l.c
ai
gm
Dilated Cardiomyopathy 00:36:25
@
56

Causes :
t4
chi

Genetic (M/c) :
ra
al

• AD.
r aw

• Mutation : Truncated variant (Tv) titin > myosin heavy chain 7 (MYH-7).
ag
|
w

Peripartum cardiomyopathy :
ro
ar

• Best prognosis. • Mx : Avoid future pregnancies

M

• Risk factor : ↑Age at pregnancy.

©

(Recurrence).
Drug induced :
• Worst prognosis.
• Anthracyclines : Doxorubicin, daunorubicin.
- 7 + 3 (AML). - R-CHOP.
- ABVD (Hodgkin’s lymphoma). - ALL.

Alcohol :
• Good prognosis (on stopping). • Risk factor : ACE polymorphism.

Sarcoidosis
M/c type of heart failure : DCM.
Hemochromatosis
Pheochromocytoma.

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 64 Medicine

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

Deficiencies :
• Selenium (Keshan’s disease). • Carnitine.
• Thiamine.

Toxins :
• Lead. • Mercury.
• Cocaine. • Anabolic steroids.
Pathophysiology :

Thin, roomy, dilated LV

Systolic defect

om
Inadequate contraction Inadequate relaxation

l.c
ai
+ Cardiomegaly = CCF.

gm
Forward symptoms. @ ↑LVEDP
56
t4
hi

Backward symptoms :
c
ra

• Ascites.
al
aw

• Edema.
r
ag

• ↑JVP.
|
w

Complications :
ro
ar

Cause of HFrEF.
M
©

1. Atrial fibrillation : Consistently ↑HR (Neurohormonal mechanisms)

Arrhythmogenesis

Sudden cardiac death.

2. Thromboembolism.
3. Acute decompensated heart failure (ADHF) : D/t LRTI (M/c).

Management :
Investigations :
• ECG :
- Low voltage in limb leads. - Sinus tachycardia.
- High voltage in chest leads. - Poor R wave progression.
• Echo : Thin, roomy/dilated, hypocontractile LV.

Treatment : Similar to treatment of heart failure.

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 Heart Failure and Cardiomyopathies 65

Acute Inflammatory Cardiomyopathy/Myocarditis : ----- Active space -----

Causes :
Infection (M/c) : HHV-6 > Trypanosoma cruzi.

Clinical features :
• Dyspnea.
• Angina (With normal coronaries).
• Hypotension unresponsive to fluid.
• ↑↑ HR.

Investigations :
• ECG : Non specific ST/T changes. • Angiogram : N coronary arteries.
• Trop-I : ↑↑. • Echo : Dilated LV, ↓EF.

om
Treatment : Supportive (Complete rest).

l.c
ai
gm
Note :
@
Steroids only useful in chronic inflammatory cardiomyopathy (Sarcoidosis).
56
t4
hi

Hypertrophic Cardiomyopathy
c

00:48:40
ra
al
aw

• Thickening of non dilated left ventricle > 15 mm.

r
ag

• Absence of other cardiac/systemic conditions producing LV hypertrophy.

|

• AD.
w

Note :
ro

• M/c genetic cardiovascular disease.

ar

Athletes :
M

• M/c cause of sudden cardiac death.

©

• Hypertrophy < 12 mm.

• Mutation : Myosin heavy chain > myosin • N diastolic filling &
binding protein c. cavity size.
• Males = Females : Females have ↑risk of progression. • Improves with rest.

Clinical Course :

Asymptomatic (95 - 99%). Complications (1 - 5%) :

• Sudden cardiac death.
• Progressive cardiac dysfunction.
• Arrhythmias (A. fib).
Features of Hypertrophy :
1. Asymmetric :
Hypertrophy of septum & anterior wall of LV (Posterior wall spared).
2. Inappropriate : Absence of ↑afterload.
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 66 Medicine

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

3. Left ventricular outflow tract obstruction (LVOT) :
Rule of 1/3rd :

No obstruction Dynamic obstruction Fixed obstruction at rest

(1/3rd). (1/3rd). (1/3rd).
Pathophysiology :
Diastolic dysfunction :
LVH ↓Cavity size ↑LVEDP ↑LAP

↑PCWP ↑Contribution of LA to
cardiac output (20% 40%)
Dyspnea on exertion

om
Atrial remodelling

l.c
(D/t ↓duration of diastole).

ai
gm
Atrial fibrillation (M/c sustained arrhythmia)
56
@
t4

Absent contribution of
chi
ra

LA to cardiac output(40% 0)
al
aw
r
ag

Hemodynamic compromise.
|
w
ro

Systolic motion of the anterior mitral leaflet (SAM) :

ar
M

Asymmetric septal hypertrophy (ASH)

©

Projects into the LV outflow tract (LVOT)

Narrow LVOT

↑Velocity across LVOT

Low pressure zone on either sides of jet

Anterior mitral leaflet sucked into low pressure zone

after 2/3rd of systole

LVOT obstruction.
Angina with normal coronaries :
Microvascular angina/small vessel disease Silent myocardial ischemia.
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 Heart Failure and Cardiomyopathies 67

Histopathology : ----- Active space -----

Myofibril disarray in HCM

Clinical Findings :
Symptoms :

om
• Dyspnea on exertion (M/c)

l.c
• Microvascular angina

ai
D/t LVOT obstruction.
gm
• Syncope 56
@
• Palpitations (D/t atrial fibrillation)
t4
chi

Signs :
ra
al

• Pulse : Pulsus bisferiens.

r aw

- 2 peaks in systole : Percussion wave (P) > tidal wave (T).

ag
|

- 2nd peak d/t SAM.

w
ro

• Apex :
ar
M

- Shifted out. - Double apical impulse (SAM).

©

• Heart Sounds :
- S1 : N . - S3 : + (↓Filling of noncompliant ventricle,↑ESV).
- S2 : Reverse split (P2-A2). - S : + .
4
• Murmurs :
- Ejection systolic murmur at lower left sternal border : LVOT obstruction.
- Pan systolic murmur at apex : SAM 2° MR.

Note :
Pulsus bisferiens also seen in :
• AR P=T
• AR + mild AS P < T

LV-aorta Gradient (Subaortic) :

• LVOT obstruction ↑LV pressure LV-aorta gradient created.
• Indicates severity of HCM.
• > 30 mmHg : Severe.
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 68 Medicine

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

Factors affecting LV-aorta gradient :
Factors and mechanisms Clinical implications in Mx
Preload :
↑Preload
• ↑Hydration
↑Cavity size
• Avoid diuretics
• Avoid venodilators
Wider LVOT

↓Gradient
Afterload :
↑Afterload

Resistance to blood flow out of LV

Avoid active control of hypertension

om
↑LV cavity size

l.c
ai
↓ Gradient

gm
Force of contraction : @
56
↑Force of contraction
t4
hi

↓Force of contraction by :
c

Narrowing of LVOT
ra

• Avoid moderate-heavy activity

al

• Digoxin : Contraindicated.
aw

↑Obstruction
r
ag
|

↑Gradient
w
ro
ar
M

Effect of manoeuvres & drugs on LV-aortic gradient & murmur :

©

↑LV-aorta gradient ↑Intensity of murmur.

Manoeuvres and drugs Effect on murmur
↓ Preload
• Valsalva
↑Intensity of murmur
• Standing
worsening of heart failure
↓ Afterload
Amyl nitrite
↑Intensity of murmur
↑Force of contraction
• Isoproterenol
• Inotropes
↑Intensity of murmur
↑Afterload
• Hand grip
• Phenylephrine
↓Intensity of murmur

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 Heart Failure and Cardiomyopathies 69

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

All murmurs ↓with Valsalva/standing except :
1. HCM : ↑Intensity of murmur.
2. MVP : ↑Duration of murmur.

Treatment of HCM :
• β blockers
• CCB :
1st line.
- Verapamil
- Diltiazem
• Disopyramide (Class 1A antiarrhythmics).
• Septal myomectomy : In medically refractory cases.
• Implantable cardioverter-defibrillator (ICD) :

om
- Family h/o sudden cardiac death.

l.c
- H/o ventricular tachycardia.

ai
gm
- Unexplained syncope.
@
56
- LV hypertrophy > 30 mm.
t4
hi

Restrictive Cardiomyopathy
c

01:22:34
ra
al
aw

Pathophysiology :
r
ag

Stiff, non-compliant ventricles

|
w
ro
ar

↑↑RVEDP
M
©

↑RAP

Symptoms of RHF (Ascites, edema, JVP, hepatomegaly).

Causes :

Non infiltrative : Infiltrative

• Diabetes mellitus.
• Scleroderma. Intracellular deposits : Intercellular deposits :
• Hemochromatosis (Iron). • Amyloidosis (M/c cause).
• Fabry’s disease (Glycosphingolipid). • Sarcoidosis.
• Pompe’s disease (Glycogen).

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 70 Medicine

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

Amyloidosis Causing RCM :
1. Primary amyloidosis (AL)
2. Transthyretin related (ATTR) :
- Wild type/senile systemic amyloidosis.
- Mutant type/familial amyloid polyneuropathy.

Clinical features :
• Biventricular hypertrophy (L > R)
• Low voltage complexes on ECG
• Biatrial dilatation

Investigations :
IOC : Cardiac MRI Glittering of myocardium (Sparkle sign).

om
Takotsubo Cardiomyopathy 01:30:00

l.c
ai
gm
AkA :
@
• Apical ballooning syndrome.
56
t4

• Neurogenic myocardial stunning (↑Sympathetic activity ↑HR).

chi

• Broken heart syndrome.

ra
al
aw

• Stress induced cardiomyopathy.

r
ag

• Catecholamine induced cardiomyopathy.

|
w

Presentation :
ro
ar

• Middle aged females (M/c)

M
©

• Transient LV dysfunction (Mimics MI/ACS)

Investigations :
• ECG : Non-specific ST/T changes.
• Elevated Trop-I.
• Echo :
- Apex : Ballooning & hypocontractile.
- Base : Hyper contractile.
• Angiography : N coronaries.

Prognosis :
• No long term complications.
• Short term complications similar to MI.

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 Pericarditis & Cardiac Tamponade 71

PERICARDITIS & CARDIAC TAMPONADE ----- Active space -----

Chronic Constrictive Pericarditis vs.

Restrictive Cardiomyopathy vs. Tamponade 00:00:31

Chronic constrictive Restrictive Tamponade

pericarditis cardiomyopathy (Acute phenomenon)
• Repeated episodes of
acute pericarditis (M/c)
• TB
Cause - Trauma
• Histoplasmosis
• IgG4 related disease

om
• Radiation

l.c
ai
Rock like pericardium Rapid ↑ in

gm
Rigid, thickened, calcific intrapericardial pressure
with adhesions @
56
t4

Pathophysiology - Compression of heart

hi

Diastolic dysfunction : (Small heart)

c
ra

Last 2/3rd
al
aw

(D/t ↓pressure transmission) Holodiastolic dysfunction

r
ag

+ (1/3 cases : D/t

rd
|

Pulsus paradoxus exaggerated ventricular - +

w
ro

interdependence)
ar
M

Prominent y descent + - -
©

Prominent x descent + - +
Kussmaul’s sign + + -
Pericardial knock + - -
S3 - + -
Low voltage complex + + +
Electrical alternans - - +
Thickened pericardium + - -
Pericardial calcification + - -
RV size Normal Normal Small
Elevation & equalization + (Post 1/3rd of diastole) - +
of diastolic pressure

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 72 Medicine

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

Chronic constrictive Restrictive Tamponade

pericarditis cardiomyopathy (Acute phenomenon)

• Other c/f
RV failure features :
- Ascites
- Edema
• Common triad seen :
- Hepatomegaly
- Hypotension
• IOC : MRI
- Obstructive shock
• Ventricular pressures :
- Dyspnea
Square root sign + :
Other features - • Tachycardia
• Beck’s triad :
Pericardial knock - Hypotension
(Post 1/3rd of diastole) - Muffled heart sounds

om
- ↑JVP

l.c
ai
gm
• Elevation & equalization of
pressure in all 4 chambers @
56
t4

Rx Pericardiectomy - Emergency pericardiocentesis

chi
ra
al
r aw
ag
|
w
ro
ar
M
©

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 Arterial Pulses, JVP and Heart Sounds 73

ARTERIAL PULSES, JVP AND HEART SOUNDS

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

Arterial Pulse 00:00:23

• Pressure wave.
• Origin : Aorta.
• Velocity : 5 m/s (Faster than column of blood : 50 cm/s).
• Assesses : LV performance and reaction of vascular system.

Wave :

om
l.c
ai
gm
@
56
t4
chi
ra

P : Percussion wave ∝ Stroke volume

al
aw

T : Tidal wave (Aortic recoil)

r
ag

DN : Dicrotic notch (Corresponds to : S2 )

|

D : Dicrotic wave (Peripheral vascular resistance)

w
ro

Arterial stiffness :
ar
M

Cushioning effect of vessels lost T

©

P
Prominent tidal wave
D
DN
↑Central systolic BP :
Best marker for target organ damage. Pulse wave : Stiff vessel

Abnormalities of Pulse 00:05:05

Based on

Rate and rhythm Volume and amplitude Character

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 74 Medicine

----- Active space ----- Rate and Rhythm :

Sinus tachycardia : Sinus bradycardia : Relative bradycardia :

• Myocarditis. • Cushing’s reflex (↑ICT). • Rate of heart rate rise :
• Anterior wall MI. • Inferior wall MI. < 10 beats per 1° rise in
temperature.
• Causes :
- Typhoid.
- Legionella.
- Q fever.

Volume and Amplitude :

om
AS AR : MR :

l.c
Collapsing pulse : Pseudocollapsing pulse :

ai
(High volume) (Normal volume)

gm
Severe AS : Very severe AS :
Pulsus tardus : Pulsus parvus et tardus : @
Ill sustained peak Well sustained apex
56
t4
hi

Rap

Rap
e

e
rok

rok
c
ra

i
dd

dd
pst

pst
al

(Reaches desired (Does not reach

du

du
own

own
aw

i
amplitude with ↑ time) desired amplitude)
Rap

Rap
stro

stro
r
ag

ke

ke
|
w

Character :
ro
ar
M

Conditions Features
©

P>T HCM
Pulsus
T=P Severe AR 2 peaks in systole
bisferiens
T>P ± mild AS
• Alternating high & low volume pulse
Pulsus alternans LV failure
• Regular rhythm
• Normal beat alternating with
Bigeminal pulse Ectopics premature contraction
• Irregular rhythm
1 peak in systole & 1 peak in diastole
Pulsus dicroticus LV failure
(D/t ↓CO ↑PVR)
• Cardiac tamponade
• Constrictive pericarditis (1/3 cases)
Pulsus paradoxus • COPD SBP ↓ by > 10 mmHg on inspiration
• SVC obstruction
• Pulmonary embolism
Reverse pulsus • Intermittent positive pressure ventilation (IPPV)
SBP ↑ with inspiration
paradoxus • HCM

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 Arterial Pulses, JVP and Heart Sounds 75

T>P P>T ----- Active space -----

Pulsus bisferiens

Bigeminal pulse Pulsus alternans

Jugular Venous Pulse 00:13:02

om
Height of vertical column of blood above sternal angle at 45°.

l.c
ai
Elevated : > 3 cm of H2O (or) RAP > 8 cm of H2O.
gm
Significance : @
56

• To assess RAP.
t4
hi

• Abdomino - jugular reflex + : Indicates impending right heart failure

c
ra
al

(↑JVP ≥ 3 cm of H2O for > 10 seconds).

aw
r
ag

Wave Form :
|
w

Waves Interpretation a
ro

c
ar

a Atrial contraction x
M

v
©

x, x’ Atrial relaxation x’
c Small tricuspid bulge y
JVP
v Atrial filling S1 S2
y Atrial emptying JVP wave form

Abnormalities 00:18:45

Prominent Giant/cannon
Absent
(↑RA pressure) (Atria contract against closed TV)
• RVH
• PAH • VT with AV dissociation :
• A-fib
a wave • Tricuspid stenosis/Tricuspid valve myxoma Irregular
• Hyperkalemia
• Restrictive cardiomyopathy (RCMP) • AVRT/AVNRT : Regular
• Chronic constrictive pericarditis (CCP)
• TR
• CCP
x descent • RV failure -
• Cardiac tamponade
• RCM
: Kussmaul sign +ve (↑JVP with inspiration)
Medicine • World of Revision • v2.0 • Marrow • 2025
 76 Medicine

----- Active space ----- Prominent Giant/cannon

Absent
(↑RA pressure) (Atria contract against closed TV)
• TR
• Hypovolemia
v wave • ASD -
• Hypotension
• RV failure
y wave CCP - -

om
l.c
ai
gm
Large a wave 56
@ Regular cannon waves
t4
chi
ra
al
r aw
ag
|
w
ro
ar
M
©

CV wave Tamponade and

constrictive pericarditis

Valvular Heart Disease : Findings 00:25:16

Diseases Pulse JVP

Severe Pulsus tardus
AS Normal
Very severe Pulsus parvus et tardus
AR Collapsing Normal
MS - Prominent a wave
MR Pseudocollapsing Normal

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 Arterial Pulses, JVP and Heart Sounds 77

Heart Sounds 00:27:00 ----- Active space -----

Identified on the basis of Intensity (Loudness) : dB.

Pitch (Frequency) : Hz.

Types :
High frequency Low frequency
• Dull/rough rumbling
• Soft blowing
Features thud-like
• Over wider area
• Associated with thrill
Causes High pressure difference Low pressure difference
Heard with Diaphragm of stethoscope Bell of stethoscope
• Heart Sounds :

om
- S3

l.c
- S4

ai
gm
Most heart sounds - Tumor plop @
Examples
56
and murmurs (MR) • Murmurs :
t4

- MS
chi
ra

- TS
al
aw

- Austin-Flint
r
ag

Mixed frequency :
|

Low frequency Radiates Carotid.

w

AS (Harsh murmur)
ro

High frequency Radiates Apex. (Gallavardin phenomenon)

ar
M
©

First Heart Sound (S1) 00:30:50

Cause :
Closure of AV valves :
Beginning of systole : Contraction of Formation of zone Tensing of
annulus of coaptation leaflets (S1).

Factors affecting the Intensity :

• Integrity of valves.
• Position of leaflet at end of diastole.
• Velocity of contraction.
• Timing of closure.
• Rate of rise of pressure (dP/dt) during IVC.

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 78 Medicine

----- Active space ----- Abnormal S1 :

S1 Conditions Mechanisms
AR Premature valve closure
• Loss of leaflet integrity
MR
Soft • ↓dP/dt
Calcific MS Immobile leaflets
Infective endocarditis Perforation of leaflets
• Leaflets far apart
MS
Loud • Delayed high velocity closure
Thin chest -
• Atrial fibrillation
Variable -
• VT with AV dissociation

om
Sail sound Ebstein anomaly Loud T1

l.c
ai
gm
Second Heart Sound (S2) 56
@ 00:41:20
t4

Cause : Hangout interval :

chi

Protodiastole : • A2 - P2 split (50 ms) :

ra
al

30 ms Widens with inspiration.

Point of crossover
aw

Aorta closure (A2)

r

80 ms • Depends on :
ag

of pressures PA closure (P2)

|

- Pressure beyond valve.

w
ro

- Distensibility of vessel.
ar
M

Factors affecting the Intensity :

©

• Pressure beyond valve : ↑Pressure Loud S2.

• Flow across valve : ↑Flow Loud S2.
• Dilatation of vessel beyond the valve : ↑Dilatation Loud S2.

Abnormal S2 :
S2 Conditions
• Systemic HTN
• Hyperkinetic states
Loud S2 (A2)
• AS : Bicuspid aortic valve
• AR : Root causes
• AS : Degenerative calcific
Soft S2 (A2)
• AR : Leaflet causes

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 Arterial Pulses, JVP and Heart Sounds 79

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

S2 Conditions
Loud P2 MS : Pulmonary HTN
• Atrial septal defect
Fixed
• RV failure
Wide split • LV pacing
(Inspiration & expiration : Early A2 • Left sided ectopics
Standing position) Variable • MR
• RBBB
Delayed P2
• Pulmonary HTN with RV failure
• AS
• HCM
Delayed A2

om
• AR

l.c
Reverse split/

ai
• LBBB

gm
Paradoxical split
@ • Right sided pacing
(Only expiration)
56
• Right sided ectopics
t4

Early P2
hi

• TR
c
ra

• WPW syndrome : Type B

al
r aw
ag

Diastolic Added Sounds 00:49:28

|
w
ro

Mnemonic : O P Time 3 to 4.
ar
M
©

Early : Mid-late : Late :

• Opening snap. S3 S4
• Pericardial knock.
• Tumor plop.
Opening Snap :
↑LAP AV valve opens with noise.

Seen in :
1˚MS with :
• Good LV function.
• Mobile leaflet.

S2- OS interval :
• ↑LAP ↓Interval Loud OS.
• ∝ 1/Severity of MS.
Medicine • World of Revision • v2.0 • Marrow • 2025
 80 Medicine

----- Active space ----- S3 :

Prerequisites :
• ↑Filling of hypercompliant ventricle
(or)
• ↓Filling of non-compliant ventricle Across non-stenosed valve.
(or)
• ↑ESV

Conditions :
• LV > RV failure. • AS.
• LVH. • MR ± heart failure.
• RCM. • AR + heart failure.
• RVH.

om
S4 :

l.c
ai
gm
Prerequisites :
• Healthy atria. @ • Pumping into :
56
t4

• Sinus rhythm. - Hypertrophic

chi

• Non-stenosed valve. - Non-compliant Ventricle.

ra
al

- Non-dilated
raw

Condition : AS.
ag
|
w

Systolic Added Sounds

ro

00:57:47
ar
M

Systolic Clicks :
©

Ejection clicks : Non-ejection clicks :

Mitral valve prolapse :
Valvular : Vascular : Dynamic auscultation Click moves closer to S1.
• Opening of aortic valves : • Aneurysms. (Standing/Valsalva)
- AS : Bicuspid aortic valve.
• Pulmonary stenosis.
Note :
• Dynamic auscultation : ↓es all heart sounds except MVP & HCM.
• Right sided heart sounds : ↑es with inspiration.
(Exception : Pulmonary ejection click ↑es with expiration)
• Brockenbrough sign :
- Seen in HCM.
- VPC ↓Pulse volume.
Medicine • World of Revision • v2.0 • Marrow • 2025
 Valvular Heart Disease 81

VALVULAR HEART DISEASE ----- Active space -----

Anatomy of Valves :
Aortic valves Mitral valves
Leaflets 3 2
Commissures 3 2
Fibrous annulus 1 1
Chordae tendineae - +
• Antero-lateral :
Papillary muscle - Dual blood supply
• Postero-medial : RCA

om
l.c
Surface area 3 - 4 cm2 4 - 6 cm2

ai
gm
Pathology : @
56
t4
chi
ra

In closure of valves In opening of valves

al
r aw
ag

Mitral regurgitation. Aortic regurgitation. Mitral stenosis. Aortic stenosis.

|
w
ro

Comparison of Valvular Diseases

ar

00:00:47
M
©

(Table in next page).

Mitral Valve Prolapse (MVP) 00:39:50

• Prolapse (Leaflets bulge into atria) + Click + murmur.

• MR + / - .
• D/t myxomatous degeneration (M/c).

Pathophysiology :
↓Cavity size

↓Stretching of chordae

↑Prolapse

Click towards S1 + ↑Duration of murmur.

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 82

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

Aortic stenosis (AS) Aortic regurgitation (AR) Mitral regurgitation (MR) Mitral stenosis (MS)
Medicine

Diastole (End of IVC)

Systole Systole (During IVC)
(End of isovolumetric Progressive commissural
contraction) © Diastole Leaflet incompetence fusion
M (Zone of coaptation not formed)
Patho- ar
Stenosed valve Incompetent/leakyro valve leaflets Stenosed valve
physiology w
(Incomplete opening) | Blood leaks back from LV to LA (Incomplete opening)
Blood leaks back from aaorta
gr to LV (↓↓Afterload)
↑LV-aorta gradient aw ↑LA-LV gradient
(∝ severity) al ↑Blood from LA to LV
ra ↑LA pressure (LAP)
ch
• Acute AR : it4
- Infective endocarditis 56
- Ruptured sinus of Valsalva •@Acute
gm MR : Right coronary
Inflammation - Aortic dissection infarction (Postero-medial
a
papillary
il. muscle rupture)
• Chronic AR : co
• Chronic MR Acute rheumatic fever
Degeneration & calcification : m:
(15 - 20 yrs)

Medicine • World of Revision • v2.0 • Marrow • 2025

• Elderly : Tricuspid valve
+
• NOTCH-1 defect : Valve affected : Root affected :
Etiology 1°/organic MR 2°/functional Valvulitis
Bicuspid valve • RHD (M/c) • Takayasu arteritis
• Quadricuspid • Syphilis (Leaflet/chordae MR (Annulus
affected) : affected) : Rheumatic heart disease
Aortic sclerosis valve • Marfan’s syndrome
• Rheumatic LV failure (MS + MR > MS + AR > AR + AS)
+↑↑Gradient • Takayasu • Ehlers Danlos
arteritis (valve syndrome • MV prolapse
AS • SLE/RA Annular
& root) • Behcet’s syndrome
• Ankylosing • Cogan’s syndrome dilatation
spondylitis • IgG4 related disease
 AS AR MR MS
Compensatory LV concentric hypertrophy
LV eccentric hypertrophy with dilatation -
mechanism (LVH)
• Mild to moderate AS :
Asymptomatic
• Progressive MS :
• Severe AS (40/4/1 rule) : • Mild/moderate AR/MR : > 1.5 cm2 VSA
- Symptomatic/
- Palpitations + / - • Severe MS :
asymptomatic
- EF↑© - 1 - 1.5 cm2 VSA
- LV-aorta gradient : M
Grading • Severe AR/MR - Asymptomatic/
≥ 40 mm Hg ar : LV failure
- EF : Normal/↓
ro symptomatic
- Peak flow velocity (PSV)
- LV end diastolic
w pressure (LVEDP) :↑ • Very severe MS :
across valve : ≥ 4 m/s |
a
- LV end systolic volume (LVESV) : ↑ - < 1 cm2 VSA
- Valve surface area (VSA) : gr - LV systolic failure
< 1 cm² aw
• Very severe : LV failure al
ra
• Severe AS (ASD 5/3/2) : • Severe AR : ch
- Angina ≥ 5 yrs Valve not - Angina : Nocturnal (↓HR) it4 • Dyspnea : Worsens with
- Syncope ≥ 3 yrs replaced - Dyspnea : If LV failure
56 exertion (↑HR)
@ • Severe MR : • Severe MS :
- Dyspnea ≥ 2 yrs - Palpitations gm
Death Dyspnea (LVEDP ↑) - Rt. heart failure
• AR + exercise : Improves symptoms (↑HR) ai
• Acute
l.c MR : - Theory of 2nd stenosis :
Clinical • AR + ↑BP :

Medicine • World of Revision • v2.0 • Marrow • 2025

• AS + ↑BP : Masks gradient Pulmonary
om edema + Pulmonary HTN
Symptoms (Aim to ↓BP) ↑Lv-aorta gradient Worsens (Good
hypotension
• AS + Atrial fibrillation : control required)
• Acute AR : Pulmonary edema + ↓Blood to LA
Loss of atrial contribution
to CO cardiogenic shock
Transient improvement in
Acute AR/MR : Frank pulmonary edema in cardiogenic shock symptoms
Hemodynamic compromise
Valvular Heart Disease
83

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

 84

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

AS AR MR MS
Severe Very severe
Medicine

• Collapsing pulse :
- Rapid upstroke & rapid
downstroke Pseudo-collapsing pulse :
© • Rapid upstroke & rapid
M +
Ill-sustained
ar peak downstroke • Normal
Pulse Pulsus parvus + • Irregularly irregular
Pulsus tardus - ↑Volume row
et tardus • Pulsus bisferiens Well-sustained peak in A. fib
Desired |: Severe AR ± mild AS
T agP T • Normal volume
amplitude P ra
or w Pulse
al
P<T P = T ra
Time Time ch
it4
• Wide pulse pressure 56
@
BP Needs to be controlled • Hill’s sign : gm -

Clinical sign :
Lower limb BP - Upper limb BP > 20 mmHg a
il.
JVP - co ↑, Prominent a wave
m
• Slightly displaced laterally • Displaced down & out (Cardiomegaly) • Displaced laterally
Apex

Medicine • World of Revision • v2.0 • Marrow • 2025

• Heaving apex • Hyperkinetic apex • Tapping apex
S1 Normal Soft Loud
• Loud S2 : Bicuspid AV • Loud A2 : Root cause • Loud, palpable P2
S2 • Soft S2 : Tricuspid AV • Soft A2 : Valve cause Wide Split S2 : Early A2 • Wide variable split S2
• Reverse split S2 • Reverse split S2 (Severe MS)
+
S3 + + : Severe AR (Failure) Opening snap (OS) + :
(Failure + / - )
Short S2-OS (∝ Severity)
S4 + - -
 AS AR MR MS
• Ejection systolic murmur • Mid diastolic murmur
(ESM) : (MDM) :
- Late systolic accentuation • Early diastolic murmur (EDM) : - Duration ∝ severity
- Components : Pansystolic murmur (PSM) : - Presystolic accentuation
- High pitched
• Same gradient (Lost in A. fib)
Murmurs - Site : Neo-aortic area
• High pitched & soft blowing • PSM : Tricuspid
- Diastolic decrescendo
Low pitch High pitch regurgitation
• Austin-Flint murmur : Low pitched
into carotid into apex : © (Carvallo sign)
Gallavardin M • Graham Steel murmur :
phenomenon ar Pulmonary regurgitation
ro
• ECHO : 40/4/1 rule w
• CT aortogram : |
a Transesophageal ECHO :
Ix Bicuspid aortic valve ECHO gra ECHO
w Detect LA thrombosis
(Rule out aortopathies) al
• Angiogram : Before Sx ra
ch
it4 Sx : • β blockers (Life-saving) :
56 • Mitral valve repair (M/c) • Warfarin :
Sx/TAVI : @
Sx : • gIndications : - A. fib
• Aortic valve replacement m
• Aortic valve replacement (AVR) - aAll symptomatic - LA clot
(AVR) with bioprosthetic valve
• Indications : il.
- Asymptomatic if (60/40 • Percutaneous mitral
• Indications :

Medicine • World of Revision • v2.0 • Marrow • 2025

- All symptomatic
co balloon commissurotomy
- Symptomatic severe & rule) m :
Rx - Asymptomatic if (55/50 rule) : 1. EF : < 60% • Sx :
very severe AS
1. EF < 55% 2. LVESD : > 40 mm - Mitral valve replacement
- Asymptomatic severe if :
2. LVESD > 50 mm 3. Acute MR : NTG, - Indications :
1. LV-aorta gradient > 60
3. Acute AR : NTG, nitroprusside 1. Significant MR
mmHg
nitroprusside (Dilators) till surgery 2. Calcific immobile
2. PSV > 5 m/s (↓afterload) till leaflet
surgery
Valvular Heart Disease

3. LA thrombosis
85

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

 86 Medicine

----- Active space ----- ECG REVISION

ACS 00:01:28

Pathophysiology :
Plaque rupture (M/c) > erosion

Occlusion :
Large epicardial coronary vessels (> 400 μm)

Critical (Fibrin rich thrombi) Non-critical (Platelet rich thrombi)

om
l.c
ST elevation ACS Non-ST elevation ACS :

ai
gm
PCI < 2 hrs : In high risk
@
< 24 hrs : Others
56
t4

Criteria :
chi
ra

Myocardial injury : (+) Myocardial ischemia (≥ 1/5) :

al
aw

• ↑Trop I (or) • Clinical evidence. • ECHO evidence.

r
ag

• ↑Trop T. • Pathological Q waves. • Angio evidence.

|

• New onset ECG changes.

w
ro
ar

Types :
M
©

I: II : III : IV : V:
Common • Critically ill Sudden Post PCI Post CABG
• O2 supply demand cardiac death (Stent thrombosis)
mismatch

IWMI 00:05:17

RCA :
Origin : R AV sulcus.

Branches :
1. SA nodal branch : Proximal RCA occlusion Bradycardia.
2. Rt atrial branch : Occlusion Atrial arrhythmias (M/c).
Note :
Reflex vagal stimulation Bradycardia
Medicine • World of Revision • v2.0 • Marrow • 2025
 ECG Revision 87

3. Acute marginal artery : ----- Active space -----

• Supplies RV free wall.
• Determines the type of RCA occlusion :

Lesion proximal to a/c Lesion distal to a/c

marginal artery marginal artery

Proximal RCA occlusion : Distal RCA occlusion

RVMI + :
Hypotension

Clear lungs ↑JVP

4. AV nodal branch (In posterior AV sulcus) :

om
Occlusion Heart blocks (IWMI > AWMI)

l.c
ai
5. Posterior descending/posterior interventricular artery

gm
(In posterior interventricular groove) : @
56
Determine dominance :
t4
hi

If PDA arises from RCA : Rt dominance (80%).

c
ra
al

LCX : Lt dominance (20%).

r aw

RCA vs LCX Lesion (In IWMI) :

ag
|
w

Lesion RVMI PWMI ST↓ ST↑

ro
ar

V1 is equivocal/
M
©

Proximal + +/- disproportionately

RCA elevated to V2, V3 aVL > aVR Lead III > II
Distal - +/- -
LCX - + aVR > aVL Lead II > III

ECG :
Inferior leads : II, III, aVF.
PWMI : V7, V8, V9.

IWMI : RCA lesion

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 88 Medicine

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

IWMI : LCX lesion (ST↑ : II > III)

Complication :
Papillary muscle (Posteromedial) rupture 2° MR.

Mx :
First medical contact :
• ECG.

om
• Blood : Trop I/T

l.c
ai
gm
Yes PCI centre @ No
56

PCI :
t4

Yes Shift + PCI in ≤90-120 min No

hi

< 60 minutes
c
ra

Shift patient to PCI centre Thrombolysis :

al

(Angioplasty + stenting)
aw

+ PCI : 1. Tenecteplase : 0.5 mg/kg (Single bolus)

r
ag

< 90 - 120 min 2. Reteplase : 10 U 10 U

|
w
ro

Shift to PCI centre

ar
M
©

Repeat ECG (60-90 min)

70% resolution :
Successful thrombolysis

Pharmacoinvasive approach :
Pharmacological Mx : PCI : 2-24 hours

• Aspirin (Non-enteric coated) : 300 mg

+
• Ticagrelor (180 mg) > prasugrel > clopidogrel
< 24 hrs
• Sublingual nitrates Start ACE - and β-blockers.
For pain relief
• Morphine
• O2 (If hypoxic)
• Rosuvastatin : 20-40 mg

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 ECG Revision 89

Periprocedural : On discharge : ----- Active space -----

Anticoagulant (One shot) : Dual antiplatelet x 1 yr

0.5 mg/kg enoxaparin (or)
5000 U of heparin Aspirin + statin.

Thrombolysis
Continue anticoagulation x 5 days.

AWMI 00:23:42

LCA :

LCx LAD
Branches :

om
l.c
Supplied wall Leads Artery

ai
gm
D1 High lateral I, aVL LAD/LCx
S1 Septal V1 >>> V2 @ LAD
56
t4

D2 Anterior V2, V3, V4 LAD

chi

D3 Lateral V5, V6 LAD/LCx

ra
al
r aw
ag
|
w
ro
ar
M
©

AWMI, proximal to D1
Note :
Collateral circulation :
+ : Seen in ongoing ischemia ↓Severity of MI.
- : Total critical occlusion (Young patient) Sudden cardiac death.

Tachyarrhythmia 00:28:42

Cause :

Enhanced automaticity : Triggered activity : Reentry :

• Paroxysmal atrial tachycardia (PAT) • Long QT syndrome (LQTS) • AVRT (WPW syndrome)
• Multifocal atrial tachycardia (MAT) • Catecholamine induced VT • AVNRT (Normal structure heart)
• Junctional tachycardia (AV node) • A Fib
• Scar VT

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 90 Medicine

----- Active space ----- QRS Complex :

Normal/narrow QRS :
• 0.10 - 0.12 sec.
• Origin : Above bifurcation of bundle of His.
• Types :

Sinus AVNRT AVRT Atrial tachycardia : Atrial fibrillation :

tachycardia Abnormal P wave Supraventricular
2/3rd cases : QRS-T (No P wave) (Just before QRS)
1/3rd cases : P wave (Just outside QRS)

Focal Multifocal
• Short RP
(≥3 type P waves)
• Long PR

om
• Long RP

l.c
ai
• Short PR

gm
Wide QRS : @
Very wide QRS :
56

• 0.12-0.16 sec. • ≥ 0.16 s VT

t4
hi

• Origin : Above bundle of His bifurcation • Type :

c
ra

+
al

- Monomorphic (≥ 3 VPC)
aw

Bundle branch block

- Polymorphic
r
ag

• Rx :
|
w
ro

- Unstable : Synchronized DC cardioversion

ar

- Stable : Amiodarone
M
©

- Post MI : Lignocaine
RR Interval :
In narrow QRS + tachycardia :

Regular R-R Irregular R-R

AVNRT AVRT Atrial tachycardia A-Fib MAT : PAT with AV block :

M/c in : COPD patients (Seen with Digoxin
Rx :
on Theophylline therapy).
• Adenosine CCB > β-blockers.
(Rx : CCB).
• Hemodynamically unstable :
Synchronized DC cardioversion.

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 ECG Revision 91

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

Atrial tachycardia

Atrial Fibrillation 00:37:02

om
l.c
ai
gm
@
56
t4
hi

Atrial fibrillation
c

Risk Factors :
ra
al
aw

• Age. • ILD.
r
ag

• HTN. • Structural heart disease.

|

• OSA.
w
ro
ar

Mx :
M
©

Hemodynamically unstable : Hemodynamically stable :

Synchronized DC cardioversion
ECHO
(100 J Max : 200 J) LA
< 4 cm Dilated ≥ 4 cm :
Onset Permanent A-Fib
< 48 hrs > 48 hrs/unknown
Only rate control :
• β-Blockers
Only rhythm control : Anticoagulation x 3 wks
• CCB.
• Ibutilide : Normal Heart (Risk of thromboembolism)
• Amiodarone : Abnormal structure
Rhythm control :
• DC cardioversion (or)
• Pharmacological

(DOAC) Anticoagulation x 4 wks :

(Post-valvular AF ,rheumatic
valve, MS : warfarin).

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 92 Medicine

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

Note :
Synchronized DC cardioversion not done in :
• Pulseless VT.
• V Fib.
• Polymorphic VT.

Torsades de pointes :
• Polymorphic VT with ↑QT interval.
• Triggers :
- Class Ia, Ic, III drugs. - ↓K+, ↓Ca2+, ↓Mg2+.
- Terfenadine. - Hypothermia.
- Macrolides.
• Rx : Defibrillation + MgSO4 (2g).

om
l.c
ai
gm
@
56
t4
chi
ra
al
raw
ag

Torsades de pointes
|
w
ro
ar
M
©

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 Gastrointestinal Disorders 93

GASTROINTESTINAL DISORDERS ----- Active space -----

Inflammatory Bowel Disease 00:01:25

Ulcerative colitis (UC). Crohn's disease(CD).

Features :
• CD > UC; M > F. • High familial concordance : CD > UC.
• Bimodal age distribution : • Etiopathogenesis : Dysregulated
- 15-30 years (Majority). mucosal immune response.

om
- 70-90 years. • Fecal markers :

l.c
• Antibiotics in 1st yr of life : ↑IBD risk. Fecal calprotectin, lactoferrin.

ai
gm
Note : @
56

• Microscopic colitis C ollagenous colitis : A/w Sjogrens syndrome.

t4
hi

Lymphocytic colitis : Also celiac disease.

c
ra

• Diversion colitis : A/w colostomy bag use.

al
r aw
ag

Genetic Disorder Association :

|
w
ro
ar

Turners syndrome : Type 1 GSD : Early onset refractory

M
©

• Strongest (Von Gierke's). childhood IBD :

association. 1L-10 deficiency.
• Most specific : UC.
Hermansky-Pudlack IPEX (Immune polyendocrinopathy
syndrome : enteropathy X-linked) syndrome :
Wiskott-Aldrich • Autosomal • Defect in Treg cell function
syndrome : recessive. (Markers : CD3, CD4, CD25)
• X-linked d/s. • Albinism. OR
• WASP gene • Platelet • Defect in FOXP3 transcription
mutation. dysfunction. factor.
• Thrombocytopenia • Lung fibrosis. • Triad :
• Sino pulmonary - Dermatitis.
infections Recurrent - UC.
• Bleeding - Type 1 DM/thyroiditis.

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 94 Medicine

----- Active space ----- Ulcerative Colitis vs. Crohn's Disease 00:08:08

Ulcerative colitis Crohn’s disease

Smoking Causative
Association

Appendi- Protective
-
cectomy
OCP - Causative
- NOD2/CARD 15 gene (Chr 16) polymorphism

Defective innate immunity :

Etiopathogenesis • ↓Intracellular organism clearance (M. paratuberculosis)
(Dysregulated • ↓Defensins
mucosal immune • ↓Autophagy
response) • ↓Fecal bacteria

om
l.c
Overactive adaptive immune system

ai
gm
@
56
Th cell involved Th2 Th1
t4
hi

Antibody Atypical p-ANCA ASCA

c
ra

Can involve : Oral cavity to anal canal

al

• Rectum/proctitis (50%)
aw

• Ileocolitis (40 - 50%)

GI involvement • Proctocolitis (30 - 40%)
r
ag

• Ileitis (30 - 40%)

• Pancolitis (20%) : Backwash ileitis in 10 - 20%
|

• Colitis (15 - 20%)

w
ro

• Deep, discontinuous (Skip lesions)

ar

• Superficial, continuous • Asymmetrical

M

• Symmetrical • Aphthoid ulcer (Earliest)

©

• Erythematous mucosa with fine granular

surface (Earliest) Rosethorn ulcer
Gross features • Hemorrhage, edema and ulceration in mucosa • Linear serpiginous ulcer
(Endoscopy) • Inflammatory pseudo polyp • Cobblestone appearance (D/t fusion of
• ↓Vascularity Used in stellate ulcers)
• ↑Friability MAYO scoring • Garden hose/
• Lead pipe/pipe stem appearance Hose pipe appearance (Fibrosis)
• Creeping mesenteric fat
• Superficial : Mucosal & submucosal involvement • Deep : Transmural involvement
• Loss of crypt architecture • Cryptitis, crypt abscesses : +
• Paneth cell metaplasia • Pyloric metaplasia
Microscopy
• Basal plasma cells and lymphoid aggregates : • Non caseating granuloma
- Earliest marker • Mesenteric adenopathy
- Early marker for relapse • Lymphoid aggregates +

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 Gastrointestinal Disorders 95

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

Ulcerative colitis Crohn’s disease

Systemic
- + (D/t Th1)
features
Clinical features

• Ileocolitis : 1st manifestation

- Recurrent RLQ pain
Proctitis (M/c) :
- Diarrhea : Small bowel > Large bowel
Other • Fresh bleeding PR Proctocolitis :
• PA : palpable mass
features • Streaks of blood on Large bowel diarrhea
• Malabsorption features :
hard stool
D/t ileum involvement :
Vit B12, Mg & bile acid deficiency
• Stricture
• Fibrosis
• Fulminant colitis
• Obstruction
Complications/
• Abscess

om
sequelae Toxic megacolon (> 6 cm dilatation)
• Fistula :

l.c
• Relapse (90%) - Enterovesical (M/c)

ai
gm
- Perianal
Differential @
56
α methyl dopa associated colitis Behçet’s disease
diagnosis
t4
hi

• Fine mucosal granularity (Earliest)

c

•
ra

Cobblestone appearance
• Serrations
al

• Rose thorn ulcer

aw

Radiology • Superficial ulcers

• String sign (D/t fibrosis)
r

• Deep collar button/collar stud ulcers

ag

• CT : Target appearance
• Lead pipe appearance
|
w
ro

Outcome Better Poor

ar

Colorectal carcinoma
M

Carcinomas
©

associated Cholangiocarcinoma Non Hodgkin lymphoma

Recurrence
Rare +
after Sx
Correlation with disease activity/relapse
+ -
• Pyoderma gangrenosum
• Episcleritis • Uveitis
• Primary sclerosing cholangitis : IgG4 related
• Type 1 arthritis : • Type 2 arthritis :
LMAP (Knee joint SMAPu
Extraintestinal 2/3rd 5% UC predominant) • Ankylosing
manifestation • Erythema spondylitis
(CD > UC) nodosum • Pyoderma
gangrenosum
PSC Others :
• Gall stone
• Oxalate stone
• Thromboembolism

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 96 Medicine

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

Ulcerative colitis Crohn’s disease

True Love & Witts classification : Mild to moderate : Weight loss
1. Mild : < 4 episodes loose stools + blood/pus/mucus • No evidence of Dehydration
• 5-ASA (Rectal > oral) Obstruction
• Sulfasalazine (5 ASA + Sulfapyridine) : • Rx : Oral budesonide
S/e : Hypersensitivity, BM suppression - ↑Ileal release
• Mesalamine (DOC) - ↓1st pass metabolism
• Maintenance : Not needed • Maintenance : Not needed
2. Moderate : No response Moderate to severe/very severe :
• Oral 5-ASA + O ral steroid
Management
No response
• Fever
+ Azathioprine/6 mercaptopurine • Obstruction
(MP)
• Maintenance : Topical 5-ASA + Azathioprine/6-MP • Cachexia

om
• Peritoneal signs

l.c
≥ 6 episodes loose stools OR

ai
3. Severe : Anemia with ↑ESR OR • Rx :

gm
Fever with tachycardia @ - IV steroid + Anti-TNF α
56
• 1V steroid + anti TNF- α - Maintenance :
t4

Low dose methotrexate + Anti-TNF α

hi

• Maintenance : Anti TNF- α + Azathioprine

c
ra

LMAP : Large joint migratory asymmetrical pauciarticular arthritis

al
aw

SMAPu : Small joint migratory aggressive polyarticular arthritis with uveitis

r
ag

UC :
|
w
ro
ar
M
©

Pseudopolyps Lead pipe appearance

Deep collar button ulcers Toxic megacolon Granular appearance

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 Gastrointestinal Disorders 97

CD : ----- Active space -----

Cobblestone appearance Rosethorn appearance String appearance Target appearance in CT

(Fissure ulcer)
Extraintestinal manifestations :

om
l.c
ai
gm
Pyoderma gangrenosum Erythema nodosum
@
56

Note :
t4
hi

• Colorectal carcinoma :
c
ra
al

A/W IBD Sporadic

r aw
ag

Age group Young Old age

|

Inflammation
w
ro

Adenoma-carcinoma
ar

Carcinogenesis Dysplasia
M

sequence
©

Ca
Carcinoma Signet cell ring carcinoma Adenocarcinoma
Mutation p53 (Early), APC APC (Early), p53
Mortality Same
• Young person with fresh bleeding PR :
- Hemorrhoids.
- UC.
- Malignancy.
Malabsorption 00:50:28

• Global malabsorption : Protein, fat & carbohydrate.

• Predominant site of absorption : Jejunum.
• Fat : most calorie dense nutrient (most specific).
• Most consistent symptom : Diarrhea.
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 98 Medicine

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

Steatorrhea : Hallmark of malabsorption.
• ↑Fat in stool :
- Pale. - Greasy.
- Voluminous. - Foul smelling.
- Bulky.
• 72 hrs fecal fat test > 7g fat for 3 consecutive days : Steatorrhea.

Classification of Diarrhea :
Based on duration :

Acute : Persistent :
• < 2 weeks. > 2 weeks.
• Infectious etiology :
- Child : Rotavirus.

om
- Adult : Norwalk virus.

l.c
Based on mechanism :

ai
gm
Osmotic
@ Secretory
56
Malabsorbed nutrients
t4
chi

↑Osmotic load in colon

ra
al

• Toxin : ETEC
aw

Cause
↑ water influx from intestinal • Tumor : VIPoma
r
ag

epithelial cells
|
w
ro

Diarrhea
ar
M

Fasting Improvement in symptoms No improvement

©

Stool osmolar gap > 50 mOsm/kg -

Note :
Factitious diarrhea : ↓↓stool osmolarity.
Based on site :
Small bowel diarrhea Large bowel diarrhea
Cause malabsorption Inflammation (IBD/infection)
Invasive (salmonella, shigella,
Organisms Toxigenic
campylobacter)
Weight loss + -
Steatorrhea Sometimes + +
Vomiting + -
Mucus - +
Blood Melena Hematochezia

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 Gastrointestinal Disorders 99

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

Small bowel diarrhea Large bowel diarrhea
Urgency - Increased
Frequency Mild↑/ N Increased
Fecal volume Large Small

Note :
Organism Manifestation
Yersinia M/c cause of ileitis R lower quadrant tenderness
Triggers for :
Campylobacter jejuni • GBS
• IPSID (Immunoproliferative small intestinal disease)
Shigella Inflammatory diarrhoea (Affects all 4 layers)

om
Staph/Bacillus cereus/
Toxigenic diarrhoea (D/t preformed toxins)
Clostridium perfringens

l.c
ai
EHEC O157 : H7 HUS

gm
Chlamydia @
Reactive arthritis (In India : Shigella)
56
t4

• BM suppression
Typhoid
hi

• Intestine hemorrhage
c
ra
al

Non typhoid salmonella Aortitis/endovascular infection

r aw
ag

Pseudomembranous Enterocolitis
|

00:57:00
w
ro
ar

• M/c associated with : Clostridium difficile.

M

• Antibiotic associated enterocolitis

©

- M/c seen with : Cephalosporin.

- Strongest association : Clindamycin.
Progression :
Incubation period : 2 days

Enteritis : Small bowel

Colitis : Large bowel.

Toxins Associated :
• Toxin A : Enterotoxic .
• Toxin B : Cytotoxic.

Complication :
Toxic megacolon.
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 100 Medicine

----- Active space ----- Ix :

Stool tests :
• Glutamate dehydrogenase (GDH)
• Toxin A/B (ELISA)

Both +ve • GDH : +ve Both -ve

• Toxin A/B : -ve
CDI confirmed +ve NAAT (Nucleic acid amplification test) -ve CDI unlikely

Rx : CDI

+ Ileus/shock/megacolon -

Fulminant CDI : Non fulminant CDI

om
Rx : Oral Vancomycin +

l.c
IV metronidazole. Rx : Oral fidaxomycin/

ai
Oral vancomycin

gm
If severe : @
56
WBC count > 15000/creatinine ≥ 1.5
t4
hi

+ IV metronidazole.
c
ra
al
aw

Celiac Disease 01:00:40

r
ag

• AKA non-tropical sprue/Gluten sensitive enteropathy/Celiac sprue.

|
w

•
ro

Iceberg phenomenon + .
ar

• Chief antigen : Gliadin.

M
©

• Proximal small intestine involvement Fe deficiency with no blood loss.

• IBS-like symptoms : 30%.
Presentation :

Classical celiac disease (50%) : Atypical celiac ds : Silent celiac ds : Latent celiac ds :
Signs & symptoms of malabsorption : Malabsorption • Asymptomatic. • Antibodies -ve.
• Diarrhea (Consistent). symptoms - . • Antibodies +ve. • HLA DQ2/DQ8 :
• GI distension (Flatulence). +ve.
• Ascites & edema.
• Weight loss.
• Foul smelling stool.
Ca chelation
• ↑Fat in intestine Free oxalate Stones.
• ↓Vit. D : Fractures (↓BMD).
• ↓Vit. E : Ataxia/peripheral neuropathy.

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 Gastrointestinal Disorders 101

Atypical Celiac Disease : ----- Active space -----

• Iron deficiency anemia. • ↑LFT

• Vit. A/D/E/K deficiency : (Cryptogenic transaminitis/Cirrhosis).
- Vit D deficiency ↓BMD • Amenorrhea.
Osteopenia and fractures. • Impotence.
- Vit E deficiency Ataxia, • Hyposplenism
Peripheral neuropathy. (Howell Jolly bodies seen).
• Short stature & failure to thrive.

Associations :
• T1 DM. • Hypersensitivity pneumonitis
• Dermatitis herpetiformis : (Bird fancier's lung).
M/c extraintestinal manifestation. • IgA deficiency.

om
• IgA nephropathy.

l.c
• Down syndrome.

ai
gm
@
56
t4
chi
ra
al
r aw
ag
|
w
ro
ar
M

Diagnosis :
©

Biopsy + serology.
Serology :

Anti-TTG (IgA) : Anti-deaminated HLA Anti-endomysial (IgA) : Anti-gliadin (IgA) :

• 92% sensitivity. glutamine dipeptide DQ2/DQ8. 99% specificity. Poor sensitivity &
• 98% specificity. (IgG) : specificity.
Used to detect
celiac in isolated IgA Obsolete
deficiency.

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 102 Medicine

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

Histology :
• Finding localized to mucosa.
• N mucosal thickness.
• Villous atrophy.
• Crypt hyperplasia.
• Lamina propria infiltrates.

Interpretation :

Serology +ve Serology +ve Serology -ve Serology -ve

om
Histology +ve Histology -ve Histology +ve Histology -ve

l.c
ai
gm
Confirms. Celiac disease likely. 56
@ Less likely. Not celiac.
Rx :
t4
chi

Gluten free diet (Avoid barley, rye, oats, wheat) :

ra
al

90% 10%
raw
ag

Resolve clinically & Not resolved

|
w

histologically within
ro

Refractory Celiac disease :

ar

6 months
M

• Premalignant :
©

a. Esophageal squamous cell carcinoma.

b. Small intestinal adenocarcinoma.
c. Enteropathy associated T-cell lymphoma.
• Rx : Steroid.

Whipple's Disease 01:12:35

• Age : 50 - 60 years.
• M > F.
• Organism : T. whipplei (Actinobacteria) :
- Cannot be cultured.
- Gram +ve.
• HLA DRB1 13 association.

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 Gastrointestinal Disorders 103

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

Multisystem involvement :

Joints : GIT : CNS (40%) : CvS :

• First 2 - 3 years. • Mesenteric • Bad prognosis. Culture -ve endocarditis
• Large joint migratory lymphadenopathy. • Oculomasticatory/ (Mitral valve).
arthralgia (DD : • Diarrhea. oculofacial
Spondyloarthropathy). • Weight loss. myorrhythmias :
• Proximal > distal (Opsoclonus
involvement. myoclonus)
Most classic.
• Rapidly progressive
dementia (M/c) :

om
Correlate with relapse.

l.c
ai
• Progressive
gm
@ supranuclear palsy.
56
t4

Diagnosis :
chi
ra

• Upper GI endoscopy + Biopsy : (IOC)

al
aw

PAS +ve macrophages (Contain T. whipplei).

r
ag
|

Note :
w
ro

100% biopsy diagnosis :

ar
M

• Abetalipoproteinemia.
©

• Agammaglobulinemia.
• Whipple's disease.
PAS +ve organism
Management :
• Ceftriaxone (DOC) : 2g IV BD for 14 days or Meropenem.
• DOC for prophylaxis/prevent relapse : Cotrimoxazole.

Tropical Sprue 01:18:01

M/c cause of malabsorption.

Pathogenesis :
Toxigenic coliforms (E. coli, Klebsiella) Fermentation products (Ethanol)
-
Folic acid absorption

Folic acid deficiency.

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 104 Medicine

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

Clinical features :
Pan intestinal involvement (Distal > proximal) :
• B12 deficiency seen.
• Hyperpigmentation seen.

Ix : Bx Similar to Celiac.

Rx :
Folic acid with tetracycline 80% improve
(20% : Chronicity).

D-xylose Test :
• Best non-invasive test : Carbohydrate malabsorption.
• Method : 25 g of D-xylose Urinary D-xylose : < 4.5 g Positive.

om
• Proximal small intestine pathology.

l.c
ai
gm
Irritable Bowel Syndrome (IBS) 01:21:20
@
56

• Response of GIT to stress. • < 45 yrs; F > M.

t4
hi

• Functional disorder. • Associated : Anxiety, depression.

c
ra
al
aw

Clinical features :
r
ag

• Crampy lower abdominal pain. • Improves with defecation.

|

• Change in form and frequency of • Nausea/vomiting.

w
ro

stool. • Mucus in stool.

ar
M
©

Excludes IBS if :
• Age > 50 yrs. • Weight loss.
• Fever. • Anemia.
• ↑ESR. • Nocturnal diarrhea.
• Blood in stool. • Steatorrhea.

Rx :
Low FODMAP diet
Fails
Drugs

Constipation predominant IBS : Diarrhea predominant IBS :

• Lubiprostone (CI- channel activator). Loperamide.
• Linaclotide (guanylyl cyclase agonist).
• Tenapanor (Na+/H+ exchange - ).
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 Hepatic Disorders 105

HEPATIC DISORDERS ----- Active space -----

Anatomy 00:00:20

Structure :
Lobule : Structural and functional unit of liver.
Portal tract : Note :
Jagged 1 NOTCH-2 pathway
• Hepatic artery (30% blood, 60% O2) Defect
• Bile duct Alagille syndrome
• Portal vein (70% blood, 40% O2)

om
Cirrhosis 00:09:20

l.c
ai
gm
Pathology :
@
56
Stellate cell (Space of Disse) Mesenchymal stem cell TGF-β (Fibrosis)
t4
hi

Lobular architecture  odules + fibrous

N
c
ra
al

septation (Cirrhosis)
raw
ag

Note :
|
w

Dubin-Johnson syndrome :
ro
ar
M

ABCC2 gene/MRP protein

©

Mutation
Canalicular membrane X B ile acid &
Bilirubin excretion.

Hepatic architecture
Clinical Progression :
Acute hepatitis Fulminant hepatic failure (FHF) : Coagulopathy + Encephalopathy.

Recovery. HBV, NASH

Chronic hepatitis Cirrhosis HCC
• Altered sleep rhythm Hepatic failure
• Muscle wasting Portal hypertension :
• Loss of libido • Ascites.
• HE.
• Varices.

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 106 Medicine

----- Active space ----- Acute Hepatitis 00:13:52

Clinical :
Prodrome : • Jaundice : Hepatic.
• 2 - 3 days • Viral enzymes : AST, ALT↑ (More specific for liver).
• Low grade fever
• Nausea/vomiting
• Myalgia
• Hypoglycemia

Hepatitis A & Hepatitis E :

HAV HEV
Incidence Children Adult

om
Route Feco-oral

l.c
Chronicity 0% risk

ai
gm
Virus Cytotoxic Immune mediated
@
56
Risk of FHF 1 in 2 lakhs 1 - 2%
t4

-
hi

FHF in pregnancy 20%

c
ra

• Relapsing
al
aw

• Cholestatic :
r

Phases Relapsing Persistent conjugated hyperbilirubinemia

ag
|
w

Pruritis
ro
ar

Ix Anti-HAV IgM Anti-HEV IgM

M
©

• Dextrose (150 g/d)

Rx
• Conservative management

Acute Hepatitis B :
• HBsAg + • 1 - 5% risk of chronicity.
Anti-HBc IgM (Surest marker).

Alcoholic Hepatitis :
• 70% mortality. • AST > ALT.
• Binge drinkers : ↑Risk. • ↑Risk of FHF.

Hepatic Failure 00:23:30

Fulminant : Acute :
Within 0 - 7 days of onset. Within 7 - 21 days of onset.
Medicine • World of Revision • v2.0 • Marrow • 2025
 Hepatic Disorders 107

Causes : ----- Active space -----

• HEV. • Alcoholic.
• HBV + HDV (5 - 20%). • Wilson’s :
• Drug/toxin : - ↓ ALP.
- Paracetamol ( > 7.5 g/day, - Coomb’s negative
72 - 96 hrs post intake). hemolytic anemia.
- Rifampicin : Idiosyncratic • Pregnancy :
response. - Acute fatty liver of pregnancy.
- Carbamazepine - Postpartum Budd Chiari
- Phenytoin Dose syndrome.
- INH independent. • Rat poison (D/t yellow phosphorous).
- PTU
Complications :

om
l.c
• ↑NH3 Cerebral edema. • MODS.

ai
gm
• Lactic acidosis. • Severe ATN.
@
• Sepsis.
56
t4
hi

Aminotransferases :
c
ra
al
aw

AST ALT
r
ag

• < 30 U/L
Normal
|

• ALT > AST

w
ro

Specificity Not specific Liver specific

ar
M

Origin Cytoplasmic & Mitochondrial Cytoplasmic

©

Viral hepatitis > 1000

Alcoholic hepatitis 300 - 500 (AST > ALT)
• >2:1 Likely ALD
AST : ALT
• >3:1 Confirmed ALD
Alcoholic + Viral/toxin ↑↑↑ (~ 8000) ↑↑↑ (~ 6000)
• Rhabdomyolysis N
↑
• Cardiac cause
• < 150 U/L
Chronic hepatitis
• ALT > AST

Conditions with AST/ALT > 1000 :

• Acute viral hepatitis. • Ischemic hepatitis.
• Drug induced hepatitis. • Acute bile duct obstruction.
• Toxin induced hepatitis.

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 108 Medicine

----- Active space ----- Chronic Hepatitis 00:29:20

Causes :
• Non-alcoholic With acute prodrome :
steatohepatitis (NASH) : M/c. • HCV : Anicteric hepatitis.
• Alcohol. • Wilson.
• Hemochromatosis. • Autoimmune.
• HBV.

Clinical :
• Asymptomatic (M/c).
• Fatigue.
Ix :

om
• Fibroscan.

l.c
ai
• ALT > AST (< 150 U/L) CLD.

gm
AST > ALT (< 150 U/L) Cirrhosis. @
56

Portal Hypertension
t4

00:37:04
chi
ra
al

↑ Systemic NO Change in gut flora Nodules :Compress

aw

sinusoids
r
ag

Splanchnic vasodilation
|

Sinusoidal defenestration
w
ro
ar

↓ Effective arterial ↓ PVR Sinusoidal constriction

M

blood volume
©

+ Hyperdynamic ↓Intrasinusoidal NO
circulation
RAAS ADH Sympathetic
NS.
↑ Flow ↑ Resistance
Na, H2O retention H2O retention

Ascites. Hyponatremia.
Sinusoidal pressure : > 6 mmHg

Portal hypertension

• Portosystemic collaterals.
• Splenomegaly (Most consistent clinical finding) :
Hypersplenism RBC, WBC, Platelet trapping,
thrombocytopenia (Most consistent
biochemical finding).

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 Hepatic Disorders 109

Decompensated Cirrhosis : ----- Active space -----

• Ascites
Portal hypertension + • Variceal bleeding OR Liver failure signs + jaundice.
• Hepatic encephalopathy

Liver failure signs :

Sign Cause
Palmar erythema & hyperpigmentation Hyperdynamic circulation
• Alopecia
• Parotid swelling ALD
• Dupuytren’s contracture
Caput medusae : Flow away from umbilicus
-
Jaundice

om
• Gynaecomastia • ↓SHBG

l.c
• Testicular atrophy • ↓5-α reductase

ai
gm
Ix : @
56
t4

Upper GI endoscopy :
chi

Moderate - severe varices Sinusoidal pressure measurement :

ra
al

• ≥ 10 mmHg : Clinically significant.

r aw

• ≥ 12 mmHg : Variceal rupture.

ag
|

Causes :
w
ro
ar

Causes WHVP FHVP HVPG

M
©

Extra hepatic portal venous obstruction

(EHPVO) :
• Children N N N
Extra hepatic
• Umbilical sepsis
• Massive UGI bleed + splenomegaly
• No cirrhosis
• Non-cirrhotic portal fibrosis (NCPF) :
- AKA Idiopathic portal hypertension
- 3rd order portal vein involved
Pre- - Young asians N N N
sinusoidal - Massive UGI bleed & splenomegaly
Intra - Risk of cirrhosis (Rare)
hepatic • Schistosomiasis
• Sarcoidosis
Sinusoidal Causes of cirrhosis ↑ N ↑
Sinusoidal obstructive syndrome/
Post- N
Veno-occlusive disease : ↑ ↑
Sinusoidal
Post bone marrow transplant

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 110 Medicine

----- Active space ----- Causes WHVP FHVP HVPG

Budd-Chiari syndrome (BCS) :
• Hepatic vein thrombosis
• Postpartum females
• Subacute :
- Abdominal pain
- Ascites
- Hepatomegaly N
Post hepatic cause : ↑ ↑
- Jaundice : 10%
• A/w :
- Polycythemia rubra vera
- PNH
- Antithrombin III deficiency
- Anti phospholipid Ab syndrome
- OCPs

om
HVPG : Hepatic venous pressure gradient.

l.c
ai
WHVP : Wedge hepatic venous pressure.

gm
FHVP : Free hepatic venous pressure. @
56
t4

HVPG :
hi
c

• HVPG = WHVP - FHVP

ra
al

• Rx for ↑ HVPG :
aw

β-blocker (Carvedilol) Not tolerated/persist Endoscopic variceal ligation.

r
ag
|
w

Variceal bleeding : Terlipressin, Octreotide.

ro
ar
M

Ascites
©

00:56:22

1st sign of decompensation.

SAAG :
Serum albumin - Ascitic fluid albumin

≥ 1.1 < 1.1

High SAAG ascites : Portal hypertension + Low SAAG ascites (10%)

Low protein High protein Low protein High protein

(Transudative) (Protein loss) (Exudative)
Cirrhosis BCS. Nephrotic Peritoneal
with portal syndrome. carcinomatosis.
hypertension.

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 Hepatic Disorders 111

Complications : ----- Active space -----

HRS :
Hepatorenal syndrome (HRS) :
• USG renal : N
↑ RAAS
• Urine analysis : N
↑ ADH IntrarenaI vasoconstriction • Creatinine : ↑
↑ SNS
• R/o other renal diseases
• Rx : Liver transplant
↑ NO Splanchnic vasodilation

Hepatopulmonary syndrome (HPS) : HPS :

Widespread pulmonary capillary dilatation • Hypoxia
Arterovenous shunting • Clubbing
• Platypnea/Orthodeoxia :
Dyspnea/↓ SpO2 on
standing

om
l.c
Spontaneous bacterial peritonitis (SBP) :

ai
gm
• Causative organism : Gram -ve (E. coli).
@
• Ascitic WBC : ≥ 500 cells/µL OR Polymorphonuclear count : ≥ 250 cells/µL.
56
t4

• Ascitic culture : +ve.

chi
ra

• No surgically treatable source of infection.

al
aw

• Rx : Cefotaxime 2g IV TDS x 5 days.

r
ag

• Prophylaxis :
|

- Norfloxacin. - Upper GI haemorrhage : 7 days.

w
ro

- Prior SBP/CP score ≥ 9 : Lifelong.

ar
M
©

Management :

Mild : Moderate : Severe :

Salt restriction. • Spironolactone : • Lasix : Drugs
100 mg 40 mg +
Large volume
400 mg 160 mg paracentesis
Fail : Fail
Diuretic resistant ascites
Transjugular intrahepatic portosystemic shunt (TIPSS)
Refractory Ascites :

Diuretic resistant : Diuretic intolerant :

Not responding to full Drug causing toxicity Full dose can’t
dose. be given.
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 112 Medicine

----- Active space ----- Hepatic Encephalopathy 01:09:34

Type A : Type B : Type C :

Also FHF. After TIPSS. Reversible portosystemic encephalopathy.
Pathology :
Glutamate
Glutamine Glutaminase Glutamine Toxic Astrocytes
NH3 (Alzheimer’s type 2)
Brain
Causes of ↑NH3 :
• No urea cycle.
• ↑ Portosystemic circulation.
• ↑ Colonic bacteria.

om
l.c
Risk Factors :

ai
gm
• ↑ NH3: @ • Alkalosis (RAAS ↑) :
56
- GI haemorrhage. - Hypovolemia.
t4
hi

- Sepsis. - Dehydration.
c
ra

- ↑ Protein diet. - Hyponatremia.

al
aw

- Constipation. - Hypokalemia.
r
ag

• Sedatives. • Uremia.
|
w
ro

West Haven Classification :

ar
M

Grade Findings
©

0 Number connection test (Psychometric test) : Diagnostic

• ↓ Attention span • Anxiety • Altered sleep pattern Covert HE
1
Begin
• Personality changes • Sleep disorder
2 • Behavioural changes • Anxiety
• Asterixis
3 • Rigidity • Hyper-reflexia
(Semistupor) • Clonus
4 • Comatose • EEG : Triphasic
Rx :
• Lactulose containing bowel wash.
• LOLA.
• Rifaximin.

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 Hepatic Disorders 113

Hepatitis B 01:18:00 ----- Active space -----

HBV : Infectious particle Dane particle (42 nm).

Transmission :
• Vertical transmission : 90%
HBeAg +ve
Mother : HBsAg +ve Chronic hepatitis.
HBeAg -ve
10%
(1 - 5%)
• Sexual
• Percutaneous (6 - 30%) Acute hepatitis Recover.
• Blood transfusion (1 per 2 lakh)

Acute Hepatitis B :

om
Incubation period : 60 days

l.c
ai
Note :
gm
Serology :
• Anti-HBc IgM (Best) : +ve. @
Hepatitis virus Incubation period
56
t4

• HBsAg : +ve. A 30
chi

• HBeAg (Qualitative marker for

ra

E 40
al

infectivity and replication) : +/-. C 50

r aw
ag
|

• Variations :
w

- Precore mutant : HBeAg not expressed - S gene mutation/ low viral load :
ro
ar

HBsAg not expressed

M
©

Measure : HBV DNA (Quantitative for

infectivity and replication) Measure : Anti-HBc IgM.

> 20,000 IU/mL > 2,000 IU/mL

in HBeAg +ve in HBeAg -ve

High infectivity
Reactivation :
Chronic hepatitis : Immune clearance Inactive carrier : Reactivation Acute hepatitis :
Immune tolerant • HbsAg : +ve • Anti-HBc IgM : +ve.
• HBV DNA : Low • HBV DNA : ↑↑.
• Enzyme : N • Quantitative HBsAg >
1000 mIU/mL.

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 114 Medicine

----- Active space ----- Serological Pattern :

HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe
Acute, ↑ infectivity + - IgM + -
Chronic, ↑ infectivity + - IgG + -
↓Infectivity
Acute + - IgM - -
Precore mutant
Window period + + + +/- +/-
Acute with S gene mutation - - IgM - -
Remote infection - - IgG - -
Recovery - + IgG - +/-
Vaccinated - + - - -

HBV Vaccine Protocol :

om
l.c
ai
Clinical condition Schedule

gm
• Unvaccinated @ Hep B vaccine : 0, 1, 2/6
• Pre-exposure prophylaxis
56
t4

• HB Ig : 0.5 mL immediately after birth

hi

Perinatal exposure
c

• Hep B vaccine started within 12 hours

ra
al

> 100 Immunized

aw

• Percutaneous Anti-HBs
10-100 Vaccine booster dose
r

• Transmucosal titre
ag

< 10 HB Ig : 0.06 mL/kg within 72 hrs + Hep B vaccine

|
w

Sexual contact HB Ig : 0.06 mL/kg within 14 days + Hep B vaccine

ro
ar

Treatment :
M
©

Acute hepatitis B :
If :
• Tenofovir alafenamide (Best)
• INR : ≥ 1.5 OR
• Entecavir
• Jaundice : > 3 mg/dL for > 4 wks.
Chronic hepatitis :
Indication for treatment :
• Cirrhosis.
• HBV DNA.
- > 20k IU/ml (HBe Ag + )
ALT > 2 times upper limit of N
- > 2k IU/ml (HBe Ag - )

Hepatitis C 01:32:58

• Acute 85% Chronic :

• Anti-HCV : +ve.
• HCV RNA : +ve.
• Ab : Anti-LKM-1.
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 Hepatic Disorders 115

Extrahepatic manifestations : ----- Active space -----

• Cryoglobinemia. • Porphyria cutanea tarda.
• Sjogren’s syndrome. • MPGN.
• Cutaneous Lichen planus.

Rx : (Velpatasvir + Sofosbuvir × 12 weeks) + Ribavirin (If cirrhosis + ).

NS5A - NS5B -

Autoimmune Hepatitis 01:36:10

• Young female.
• Also : SLE (Lupoid hepatitis).
• Presentation :

om
Acute : Chronic : Interface hepatitis
• Waxing & Waning of jaundice.

l.c
ai
• Polyclonal hypergammaglobinemia : Anti-SMA.

gm
Interface hepatitis
@
56

Antibodies :
t4
chi
ra

Type 1 hepatitis :
al

Type 2 hepatitis :
aw

• ANA : 100%. • LKM-1.

r
ag

• SMA. • ALC-1.
|

• AAA : Poor prognosis.

w

• SLA : High specificity.

ro
ar

• Atypical p-ANCA.
M
©

Note :
• LKM-2 : Drug induced hepatitis • LKM-3 : Hepatitis - D

PBC vs. PSC 01:38:04

Primary biliary cirrhosis (PBC) Primary sclerosing cholangitis (PSC)

Incidence Middle aged female Young male
Pathology Autoimmune inflammatory destruction IgG4 related fibrosing destruction
Affected area Intrahepatic bile ducts Intra & extra hepatic bile ducts
• Fatigue
Symptoms
• Pruritus
• MRCP (IOC)/ERCP
Ix Anti-mitochondrial Ab
• Biopsy : Onion skin appearance
Rx UDCA Transplantation
• Sjogrens • Hepatomegaly
A/w • Type 1 RTA • Hyperpigmentation Ulcerative colitis
• Xanthoma
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 116 Medicine

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

Onion skin appearance

Haemochromatosis & Wilson’s Disease 01:40:22

Wilson’s disease Haemochromatosis

Incidence Young male Middle aged male

om
Gene ATP 7b (Chr. 13) HFE (Chr. 6)

l.c
• Defective copper incorporation to ceruloplasmin • Hepcidin not produced

ai
Pathology
• Defective biliary excretion of copper • Uncontrolled iron absorption by ferroportin

gm
@
Chronic hepatitis :
Hepatic :
56
• Hepatomegaly
t4

• Acute liver failure • Asymptomatic

• Type 3c DM :
hi

• Fatty liver • KF ring (65%)

c
ra

Pancreatic DM
• Cirrhosis • Portal HTN
al

• Joint : H ook-like osteophytes

aw

Presentation Neural :
(Non-inflammatory)
r

• Dysarthria • KF ring (95%)

ag

• Pituitary :
|

Other manifestations :
Hypogonadotropic hypogonadism
w

• Hypoparathyroidism • Sunflower cataract

ro

• Bronze pigmentation
ar

• Type II RTA
• Dilated cardiomyopathy : Juvenile
M
©

• ↓ S. ceruloplasmin
• ↑ Ferritin
• ↑ Free Cu (Non-ceruloplasmin bound Cu ↑)
Ix • ↑ Transferrin saturation
• ↑ Urine Cu
• C282Y mutation (Gold standard)
• Biopsy : Quantitative Cu (Gold standard)
• D-Penicillamine
Rx Phlebotomy
• Zinc

KF ring Bronze pigmentation

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 Basics of Pulmonology : Structure, Mechanics & PFT 117

BASICS OF PULMONOLOGY : ----- Active space -----

STRUCTURE, MECHANICS & PFT

23 (Airway generations)
Conducting zone (1 - 16) Respiratory/alveolar zone (17 - 23)
• Respiratory bronchiole
Components Trachea to terminal bronchiole • Alveolar duct Acinus
• Alveoli
Significance Anatomical dead space (150 mL) -

Bronchi vs. Bronchiole 00:06:55

om
Bronchi Bronchiole

l.c
ai
Goblet cells + -

gm
Mucus secretion + @ -
56
Cartilage + -
t4
hi

Smooth muscles + + (Max : Terminal bronchiole)

c
ra

+ + (Upto terminal bronchiole)

al

Cilia
aw

Pseudostratified, • Pseudostratified, ciliated columnar

r

Epithelium
ag

ciliated columnar • Cuboidal, non-ciliated (Terminal bronchiole)

|
w

• Clara/club cells :
ro
ar

- Location : Terminal bronchiole. - Function : Detoxification > stem

M
©

- Structure : Cuboidal non-ciliated. cells.

• Basal cells : Major stem cells.
• Aspiration in Supine : Rt. posterior UL.
Standing : Rt. basal LL.
Major Lung Diseases 00:10:14

Parenchymal damage :
Disease Features Hypoxia ↑PaCO2 Cor pulmonale
(RVH + RV failure)
Diffuse parenchymal lung fibrosis :
Interstitial lung +
• Early : Fibrosis of interstitium + in late stage
disease (ILD) (↓DLCO)
• Late : Parenchymal damage
Bronchial asthma Airway disorder + -
It involves :
Chronic bronchitis • Large airways
+ +
(Blue bloaters) • Pulmonary vasculature
• Lung parenchyma
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 118 Medicine

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

Parenchymal damage :
Disease Features Hypoxia ↑PaCO2 Cor pulmonale
(RVH + RV failure)
Dilatation of acinus +
Emphysema
destruction of walls of air spaces + -
(Pink puffers)
(Alveolar-capillary unit affected)

Lung parenchyma : Alveoli + alveolar interstitium + vascular interstitium.

Alveoli 00:17:00

Alveolar Epithelium :

Type 1 (Squamous) : Prone Type 2 (Cuboidal) : Produces surfactant

om
to oxidative damage. (↓Surface tension).

l.c
ai
gm
Surfactant : Cleared by : GM-CSF.
@
56
t4

Classification of Lung Diseases 00:20:15

chi
ra

Diseases
al
aw

Vascular diseases • Venous thromboembolism • Pulmonary HTN

r
ag

• COPD :
|

- Chronic bronchitis
w
ro

- Emphysema
ar

- Small airway disease(↓FEF 25 - 75/↓MMEF)

M

Obstructive diseases
©

• Bronchial asthma
• Bronchiolitis
• Bronchiectasis
• Cystic fibrosis
• Intraparenchymal : ILD
• Extraparenchymal :
a. Neuromuscular :
- Myasthenia gravis
Restrictive diseases
- GBS
b. Chest wall :
- Kyphoscoliosis
- Ankylosing spondylitis
FEF : Forced expiratory flow
MMEF : Maximal mid expiratory flow

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 Basics of Pulmonology : Structure, Mechanics & PFT 119

Mechanics of Breathing 00:23:28 ----- Active space -----

1
Boyle’s law : Tidal Volume ∝
Transpulmonary pressure
Transpulmonary Pressure (TPP) :
TPP = Intrapulmonary/Intraalveolar pressure - Intrapleural pressure (-ve)
Intrapulmonary pressure : Intrapleural pressure :
+ +
+1 Expiration 0 +
Start of inspiration :
-2
0 + -2 to -3 mmHg
-3
-4
-1 Inspiration -5

om
-6

l.c
-7

ai
gm
-8 End of inspiration :
Start of inspiration : @ -7 to -8 mmHg
56
• TPP = 0 - (-2 to -3).
t4
hi

• TPP = +2 to +3 mmHg (To distend alveoli).

c
ra
al

Volume - Pressure graph :

raw
ag
Volume

|
w

ΔV = Static compliance of lung

ro
ar

ΔP
M
©

Dynamic Compliance : TPP

• Compliance with resistance.

• TPP/distending pressure overcomes resistance during distention of alveoli
(Inspiration).
Resistance due to :

Elastic recoil pressure (ERP) Surface tension (Major) :

Elastic force ↓ by surfactant.

↓ERP : Seen in ↑ERP : Seen in ILD

emphysema/COPD (D/t fibrosis).
(D/t loss of elastic attachments).
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 120 Medicine

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

Hysteresis loop :
l eft
and

Volume
p
tsu
Shif

ht

on
ig

ati
dr

p
loo
p ir
an

sis
Ex
n

re
ow

ste
sd

on
Hy
t

ati
hif

pir
S

Ins
ΔV = Dynamic compliance
ΔP
TPP

om
Obstructive Lung Diseases 00:41:25

l.c
ai
Driving pressure :
gm
• Intrapleural pressure + ERP. @
56

• N : Driving pressure > airway pressure Forced exhalation.

t4
chi
ra

Emphysema :
al
aw

↓ERP
r
ag

Driving pressure < airway pressure

|
w

In bronchioles
ro
ar

Dynamic collapse of airways

M
©

Air trapping (Final stage).

Stages of Obstructive Airway Disease :

Stage FVC FEV1 FEV1/FVC RV TLC

Hyperinflation N ↓ ↓ ↑ ↑
Air trapping ↓ ↓ ↓ ↑ N

DLCO (Diffusion Capacity for CO) :

DLCO
Emphysema ↓
Chronic bronchitis N
Bronchial asthma N /↑

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 Basics of Pulmonology : Structure, Mechanics & PFT 121

Reversibility Test : ----- Active space -----

FEV1
FVC ↓

Short-acting bronchodilator given : 100 mcg x 4 puffs

Repeat test (After 30 minutes)

+ FEV1 : ↑ by 200 mL + ↑ by ≥ 12% -

Reversibility + Reversibility -

Bronchial asthma. COPD.

Restrictive Lung Diseases 00:48:25

Intraparenchymal Extraparenchymal

om
(ILD) Neuromuscular disorders Chest wall disorders

l.c
ai
DLCO ↓ N

gm
FVC ↓ @
56

FEV1 ↓
t4
hi

FEV1
c

N /↑
ra

FVC
al
aw

RV ↓ N
r
ag

TLC ↓ ↓ N
|

RV
w

- ↑ N
ro

TLC
ar

DLCO COD : Coefficient

M

COD = N ↑
©

Lung volume of diffusion.

Approach to Lung Disorders 00:52:15

FEV1
FVC

↓ N /↑
Obstructive lung disorders Restrictive lung disorders
- Reversibility + ↓ DLCO N
COPD Bronchial Intraparenchymal (ILD). Extraparenchymal
DLCO N asthma.
↓ ↑ RV N
Emphysema. Chronic bronchitis. TLC
Neuromuscular disorders. Chest wall disorders.

Vascular disease :
• FVC • FEV1/FVC : N
N
• FEV1 • DLCO : ↓.
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 122 Medicine

----- Active space ----- VASCULAR DISORDERS OF LUNG

Venous Thromboembolism/Pulmonary Thromboembolism 00:00:15

Source of Emboli :
M/c : Femoral vein (Suprapopliteal).
Pregnancy : Pelvic vein.

Note :
M/c site of DVT : Calf veins.

Causes :

om
l.c
Inherited : Factor V leiden mutation.

ai
gm
Acquired : @
56

• Antiphospholipid antibody syndrome.

t4
hi

• Hospitalization > 96 hours (Immobilized).

c
ra
al

• Post orthopaedic surgery.

aw

• Heparin induced thrombocytopenia.

r
ag

• Paroxysmal nocturnal hemoglobinuria. Massive pulmonary embolism

|
w

• Myeloproliferative neoplasms.
ro
ar

• Adenocarcinoma.
M
©

• Heart failure.
• Pregnancy/puerperium.
Types :
Massive (60% mortality) Submassive Non-massive
RVH + + -
Hypotension - -
+
(<90/60 mmHg)
Pulmonary artery dilatation (D/t large clot)
RV dilatation/Hypertrophy ± RV failure (Acute cor pulmonale)
NT pro BNP or
Septal push Trop I :
Features -
↓LV output ↑ : High Normal :
risk Low risk
↓BP

Shock
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 Vascular Disorders of Lung 123

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

Massive (60% mortality) Submassive Non-massive
• Recurrent
• Dyspnea with clear lung pneumonia
Presentation fields (M/c) - • Pleuritic
• Syncope chest pain
• Hemoptysis

Note :
Dyspnea with clear lungs seen in :
• Pulmonary thromboembolism.
• Metabolic acidosis.
Investigations :
ECG :

om
• Sinus tachycardia.

l.c
ai
• T wave inversion : V1 to V4.
gm
Features of RV strain
• Deep S wave :V1. @
56

• R/o MI.
t4
chi
ra

ECHO : CXR : long linear

al
aw

band of atelectasis
• Findings :
r
ag

- RVH/RV dilatation.
|
w

- Septal push.
ro
ar

- Small LV.
M

• To r/o cardiac tamponade.

©

• McConnell’s sign :Hypocontractile

free wall of RV.
CTPA : Saddle
Blood enzymes : Pulmonary embolism
• NT pro BNP.
• Trop I.

CT pulmonary angiography (CTPA) :

Polo mint sign :Thin rim of contrast around
a central filling defect (D/t thrombus).

PFT : Polo mint sign

• DLCO↓.
• FVC and FEV1 : Normal.

V/Q scan : Done in pregnant women.

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 124 Medicine

----- Active space ----- Well’s Score :

Categorizes the severity for mx :

Moderate/high risk Low risk

CTPA d-dimer
+ve
CTPA.
Management :

• In suspected case : UFH 80 U/kg (or) LMWH 1 mg/kg given

In case of massive/submassive high risk/large clot burden :

• Thrombolysis : Alteplase (Recombinant tissue plasminogen activator) upto 14 days

om
l.c
(or)

ai
• Heparin infusion Switch to Warfarin
gm
After 3 @
56
months
t4
chi

New oral anticoagulants (NOAC).

ra
al
aw

• C/I of anticoagulant IVC filter.

r
ag

• In risk of bleeding Embolectomy > catheter based thrombolysis.

|
w
ro

Complication :
ar
M

• Type 1 respiratory failure.

©

• Sudden cardiac death.

Pulmonary Hypertension 00:13:38

PAP : Pulmonary arterial pressure

PAP = (C0 x PVR) + LAP PVR : Peripheral vascular resistance
LAP : Left atrial pressure
Classification :

↑ in PVR : ↑ in LAP :
Class 1 : Pulmonary artery HTN (PAH) Class 2 : D/t cardiac causes.
Class 3 : D/t chronic hypoxia (COPD)
Class 4 : Chronic pulmonary thromboembolism
(Rx : Surgery).

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 Vascular Disorders of Lung 125

PAH : ----- Active space -----

• Plexiform arteriolopathy (Arteriolar HTN).

• At rest : ≥ 20 mm Hg.

Causes : Presentation :
• Idiopathic (Major). • Symptoms :
• BMPR 2 mutation. - Fatigue.
• Systemic sclerosis (Limited scleroderma). - Syncope. D/t RV dilatation
• Infections : HIV, schistosomiasis. - Chest pain (D/t ischemia).
• Toxic rapeseed oil. • Signs :
• Fenfluramine. - Loud, palpable P2.
- Parasternal heave.
Pathogenesis :

om
Endothelial injury + vascular remodelling + thrombosis :

l.c
• ↓Nitric oxide and ↓cGMP.

ai
gm
• ↓Prostacyclin and ↓cAMP.
@
• ↑Endothelin.
56
t4
hi

Mx :
c
ra
al

• O2 therapy.
aw

• Diuretics.
r
ag

• Anticoagulants.
|
w
ro

• R/o ILD & OSA.

ar

• Based on response to vasoreactivity test :

M
©

+ -

CCB : Check NYHA class of symptoms

Nifedipine 240 mg
Class 1 to 3 Class 4

Ambrisentan (ERA) + Prostanoids :

Tadalafil (PDE 5 inhibitor). Epoprostenol,
Treprostinil.

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 126 Medicine

----- Active space ----- OBSTRUCTIVE LUNG DISEASES

Bronchiectasis 00:00:13

• Abnormal irreversible dilatation + Obliterative fibrosis of bronchioles.

Progress
(Medium sized bronchi Entire bronchi)
• M/c : Cylindrical/tubular type.

Features :

Adult : Childhood :

om
• Causes : • Cystic type.

l.c
- 30% : Idiopathic • M/c site : Upper & middle lobe

ai
gm
- 40% : TB 56
@ • Associated with :
- Rare : Sjogren syndrome - Kartagener syndrome
t4

• M/c : F > M (40 - 60 yrs) - Young’s syndrome

chi
ra

• M/c site : Left lower lobe - α-1 antitrypsin deficiency.

al
aw

Progress
r

B/L.
ag
|

Pathophysiology :
w
ro

Loss of smooth muscle & elastic tissue

ar
M
©

Abnormal irreversible dilatation

1. Loss of cilia : ↓Mucociliary clearance

2. Goblet cell hyperplasia : ↑Cough
3. Weakening of bronchial wall (Inflammatory)

2˚ infection : M/c is pseudomonas.

Variants :
• Traction bronchiectasis : Seen in ILD.
• Brock’s syndrome : Rt middle lobe affected.
• Bronchiectasis sicca (Dry) : Seen in TB.
• ABPA producing bronchiectasis : B/L proximal central lobe affected.
(ABPA ILD)
Clinical Features :
• Chronic cough with expectoration (With acute exacerbations).
• Clubbing (Childhood).
Medicine • World of Revision • v2.0 • Marrow • 2025
 Obstructive Lung Diseases 127

• Mild hemoptysis. ----- Active space -----

• Early to mid inspiratory coarse crackles
+
Diffuse rhonchi (Wheeze).
• Recurrent pneumonia.
Ix :
X-ray :
Finger in glove appearance : Tram-track appearance + mucus.
(Abnormal dilatation)
Volumetric multidetector helical CT scan (IOC) :
• Signet ring sign.
• Tree in bud pattern.
Mx :

om
• Airway clearance and postural drainage :

l.c
ai
- Hypertonic saline.
gm
- Steam inhalation. @
56

• Recombinant DNAse : For cystic fibrosis associated bronchiectasis.

t4
hi

• Resection : Localised bronchiectasis.

c
ra
al

• Macrolides (Immunomodulatory effects) : 6 - 9 months.

aw
r
ag
|
w
ro
ar
M
©

Finger in glove appearance Central bronchiectasis

Signet ring sign

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 128 Medicine

----- Active space ----- Pulmonary Eosinophilia (Eosinophilic Lung Disease) 00:13:09

Airway disease : Eosinophils Airway > parenchyma.

Features :
Broncho-alveolar lavage eosinophilia.
or
Lung tissue biopsy eosinophilia.
or
Peripheral eosinophilia + abnormal imaging evidence.
Causes :

Known : Unknown :

om
l.c
1. Parasite : 1. Acute eosinophilic pneumonia

ai
gm
• Lung fluke (Paragonimus westermani) 2. Chronic eosinophilic pneumonia :
invasion : Chocolate coloured sputum + @ • ≥ 40% eosinophils in BAL
56
t4

eosinophils in pleural fluid • X-ray Photographic negative

chi

• Loeffler’s syndrome : Hypersensitivity to of pulmonary edema (Infiltrates in

ra
al

Ascaris lumbricoides periphery with central clear areas)

r aw

2. Drugs : 3. Churg-Strauss syndrome (EGPA/AGPA)

ag
|

• NSAIDs 4. Idiopathic hypereosinophilic syndrome.

w
ro

• Nitrofurantoin
ar
M

3. Tropical pulmonary eosinophilia (D/t

©

microfilariae) : > 40% eosinophils in BAL

4. Allergic Bronchopulmonary Aspergillosis (ABPA).

Note :
Mild eosinophilia :
• Bronchial asthma.
• Cryptogenic organising pneumonia (COP)
ILD.
• Langerhans cell histiocytosis (LCH)
• IgG4 related disease.

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 Obstructive Lung Diseases 129

ABPA 00:18:25 ----- Active space -----

Causative organism : Aspergillus fumigatus.

Pathogenesis :

• Long standing Bronchial asthma (Steroid dependent)/cystic fibrosis

A. fumigatus colonizes

Type I + III hypersensitivity reaction

(I > III)

Chronic productive Mucus plugs ↑IgE Eosinophilia

cough (Contain septate hyphae)

om
Inflammation

l.c
Inflammation

ai
Migratory infiltrates

gm
Bronchial wall weakening 56
@ (Fleeting infiltrates on x-ray)
t4
hi

Bronchiectasis
c
ra

(B/L upper lobe, central, proximal type)

al
r aw
ag

Recurrent infections with exacerbations.

|
w
ro

• TH2 mediated inflammation (IL-4, IL-5, IL-13).

ar
M

Clinical Features :
©

• Recurrent asthma exacerbations.

• Fever.
• Chronic productive cough with brownish thick mucus plugs.
• Crackles/clubbing (15%).
• Fibrosis (Upper lobe) : Rare.

Criteria for Diagnosis :

Predisposing asthma/CF Obligatory criteria : Supportive criteria :

• IgE > 1000 IU/mL • Eosinophils > 500 cell/µL.
(Indicator for prognosis) • Precipitins/↑IgG Ab.
• Positive immediate • Consistent radiographic
skin test or ↑IgE Ab to opacities.
aspergillus.
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 130 Medicine

----- Active space ----- Radiological Findings :

Tram-track lines Finger in glove appearance Central bronchiectasis :

Tree in bud appearance

om
Treatment :

l.c
• Steroids : For 12 weeks.

ai
gm
• Steroid resistant Itraconazole for 16 weeks.
56
@
t4

Note :
chi

Other pulmonary manifestation of A. fumigatus :

ra
al

• Aspergilloma (In old cavitary TB).

aw
r

• Chronic cavitary pulmonary aspergillosis (CCPA) : Bronchial wall invasion in COPD.

ag
|

• Invasive aspergillosis :
w
ro

- Immunosuppression Steroids/neutropenia (Post-transplant/aplastic

ar
M

anemia/hairy cell leukemia).

©

- Angioinvasion.

Hypersensitivity Pneumonitis (HP) 00:26:19

• AKA Extrinsic allergic alveolitis.

• Involves terminal airways & alveoli.

Pathogenesis :
Lymphocyte
Repeated inhalation Type IV + Type III Non-caseating granulomas.
of organic dust hypersensitivity
(IV >> III)

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 Obstructive Lung Diseases 131

Patterns : ----- Active space -----

• Acute (Rare) : Presents as Acute Interstitial Pneumonia (AIP).

• Sub-acute (M/c) :
- Self-resolving.
- Infiltrates Diffuse
Non-migratory
Reticulonodular
• Chronic : Presents as upper lobe ILD.

Types :
Type Antigen
Farmers lung (M/c) Thermophilic actinomycetes Moldy hay
Bagassosis Thermophilic actinomycetes Moldy sugarcane

om
Bird fancier’s lung Avian droppings

l.c
ai
Malt workers lung Aspergillus clavatus Barley

gm
Hot tube/humidifier/air @
Cladosporium
56
conditioner lung
t4
hi

Investigations :
c
ra

• BAL : • Imaging :
al
aw

- Lymphocytosis.
r
ag

- CD8 : CD4 > 2 : 1

|
w
ro

Treatment :
ar
M

Steroids.
©

ABPA vs HP : Mosaic attenuation

(Head cheese pattern)

ABPA HP
• Migratory peripheral infiltrates
Diffuse alveolar -
Early • Atelectasis
interstitial infiltrates
Radiographic features • Bronchiectasis
Reticulonodular interstitial
Late Fibrosis
opacities
Skin test reactions to Aspergillus ±
+
antigens (Immediate & delayed) (Aspergillus clavatus : +ve)
IgG Aspergillus precipitins
+
(D/t type III hypersensitivity reaction)
Peripheral eosinophilia + -
Serum IgE levels ↑↑ Normal

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 132 Medicine

----- Active space ----- Bronchial Asthma 00:34:40

Exclude pure airway disease if :

• Parenchymal involvement.
• Hypercapnia (Type 2 respiratory failure).
• Pulmonary HTN.
• Cor pulmonale.
Pathogenesis :
Triggers Th2 response IL-4 IgE
IL-5 ↑ Eosinophils

Chronic airway inflammation Smooth muscle hypertrophy

(D/t Eosinophils).

om
Bronchoconstriction (Airway limitation)

l.c
ai
gm
Reversible with bronchodilator. Variable
@
56
t4

Wheeze, chest
hi

tightness.
c
ra
al

Types :
raw
ag

Based on onset :
|

• Childhood (Extrinsic).
w
ro

• Adult (Intrinsic) : A/w Samter’s triad.

ar
M

Aspirin sensitivity
©

Asthma Nasal polyps

(Severe & persistent)
Based on symptoms :
Moderate Severe
Intermittent Mild persistent
persistent persistent
Daytime symptoms - 2 - 6 days/week Daily Continuous
Nighttime symptoms - > 2/month > 1/week Daily

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 Obstructive Lung Diseases 133

Management 00:39:10 ----- Active space -----

Acute exacerbation :
Look for signs of impending
respiratory failure :
• Silent/confused
• Silent chest
• Pulsus paradoxus -
• Paradoxical breathing
• Relative bradycardia
+ -

NIV • O2 therapy
• SABA : Albuterol 2.5 - 5 mg every

om
Intubation + 20 mins (Max. 3 times)

l.c
ai
mechanical ventilation • IV Hydrocortisone 100 mg

gm
@ No response
56
t4
hi

NIV No response
IV MgSO4
c
ra

(2g over 20 mins)

al
aw

Chronic disease :
r
ag
|
w

Type Rx
ro
ar

Mild intermittent LABA (Formoterol) + ICS (As & when required)

M

Mild persistent LABA + Low dose ICS

©

Moderate persistent LABA + Medium dose ICS

LABA + High dose ICS
Inadequate response
Add :
Severe persistent • Omalizumab (Anti-IgE)
• Mepolizumab (Anti-IL5)
• Dupilumab (Anti-IL4)
• Tiotropium bromide (LAMA)

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 134 Medicine

----- Active space ----- COPD 00:45:20

• Irreversible airway disease.

• Smoking : Primary causative risk factor.

Chronic Bronchitis vs. Emphysema 00:46:34

Chronic bronchitis Emphysema

(Blue bloater) (Pink puffer)
Definition Clinical Pathological

1. Large airway changes : 1. Parenchymal involvement :

• Goblet cell hyperplasia Alveolar-capillary unit damaged

Mucus hypersecretion ↓DLCO.

om
l.c
Productive cough

ai
gm
(Neutrophils in sputum)
@
56
• Squamous metaplasia
t4

of epithelium
chi
ra
al

2. Parenchyma & pulmonary 2. Small airways involvement :

aw

vasculature : Loss of alveolar attachments

r

Pathogenesis Parenchymal involvement

ag
|

↓Elastic recoil pressure

w
ro

Type 2 respiratory failure

ar

(↓PaO2, ↑PaCO2) Hyperinflation • Hyperresonant chest

M

• Liver pushed down

©

Forceful
Respiratory acidosis expiration
Pulmonary vasoconstriction Dynamic compression
of airways
RV dilatation RV failure
↑Work of breathing
Cor pulmonale
Dyspnea.
• Cachexia
• Cyanosis (D/t ↓PaO2) • Hoover sign
Signs
• Cor pulmonale • Hyperresonance
• Pursed lips

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 Obstructive Lung Diseases 135

Chronic bronchitis Emphysema ----- Active space -----

(Blue bloater) (Pink puffer)

• TLC : Normal • TLC :↑
PFT
• DLCO : Normal • DLCO : ↓
CXR Normal ↑AP diameter
Life expectancy Less Longer
Respiratory failure Type 2 Type 1

Types of Emphysema :

Centriacinar Panacinar Paraseptal

• Involves lower lobe
• M/c • Young males
• Seen in :

om
• Involves upper lobe • Risk of spontaneous
- Non-smokers

l.c
• Seen in smokers pneumothorax

ai
- α1-antitrypsin deficiency
gm
@
56

α1-antitrypsin deficiency :
t4
hi

• SERPINA-1 gene mutation : ↑Neutrophil elastase Matrix degradation.

c
ra
al

• Pizz phenotype (Normal : PiMM).

r aw
ag

Terminal Respiratory Alveolar duct

Terminal Alveolar duct Alveolus
|

bronchioles bronchiole
w

bronchioles
ro
ar
M
©

Septum Septum

Chronic inflammation Alveoli Respiratory

and fibrosis bronchiole
Centriacinar emphysema Panacinar emphysema

Terminal Alveolar ducts & alveoli

bronchioles

Septum

Respiratory
bronchiole

Paraseptal emphysema

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 136 Medicine

----- Active space ----- Types of Respiratory Failure 00:53:35

Type 1 respiratory failure : Type 2 respiratory failure :

• Findings : • Findings :
- Hypoxia (↓PaO2). - ↓PaO2 & ↑PaCO2.
- Parenchymal involvement - : Normal PaCO2. - (A-a) O2 gradient : Normal.
- (A-a) O2 gradient : ↑. • Causes :
• Causes : - Conditions with hypoventilation
- Asthma. (Extraparenchymal).
- Bronchiectasis. - Chronic bronchitis
- Diffusion defect : (Parenchymal damage).
• Exudate.

om
• Pulmonary edema.

l.c
• Emphysema.

ai
gm
• ILD (Fibrosis). Long @
Type 3 respiratory failure : Parenchymal ↓PaO2,
56
• ARDS. term
Long term ILD & ARDS
t4

involvement ↑PaCO2
hi

(Existing type 1 failure + )

c
ra
al
aw

Management of COPD
r

00:58:11
ag
|
w

Non-pharmacological :
ro
ar

• Long term O2 therapy.

M

• Smoking cessation.
©

Pharmacological :
↑Dyspnoea
• Stable Group A : Group B :
• Mild dyspnea LABA : Formoterol, Indacaterol LABA + LAMA
• 0 to 1 moderate exacerbations or
(Not leading to hospitalization) LAMA : Tiotropium bromide

≥ 2 moderate exacerbations Group E :

or LABA + LAMA
≥ 1 leading to hospitalization +
Inhaled corticosteroids (Eosinophils > 300)
Unresponsive to ICS
Chronic Emphysema/
bronchitis smoker
Roflumilast Azithromycin
(PDE-4 inhibitor)
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 Restrictive Lung Diseases 137

RESTRICTIVE LUNG DISEASES ----- Active space -----

TGF-β Diffuse parenchymal lung fibrosis/ILD.

Classification 00:00:52

Idiopathic interstitial Autoimmune Sarcoidosis Hypersensitivity Miscellaneous

pneumonia (M/c) associated pneumonitis (HP)
associated
Idiopathic Interstitial Pneumonia :
Patterns :

om
l.c
1. Idiopathic pulmonary fibrosis (IPF)/Usual Interstitial pneumonia (UIP) : M/c.

ai
gm
2. Non-Specific interstitial pneumonia (NSIP).
3. Cryptogenic organising pneumonia (COP) : @
56
t4

- Elderly males.
chi

- Specific to Anti-synthetase syndrome (Viral fever/pneumonia-like

ra
al

presentation).
r aw

4. Desquamative interstitial pneumonia (DIP).

ag
|

5. Respiratory bronchiolitis associated ILD (RB-ILD).

w
ro

6. Acute interstitial pneumonia (COVID) :

ar
M

- Bad prognosis.
©

- Diffuse alveolar damage (DAD).

7. Lymphocytic interstitial pneumonia (LIP) :
- HIV.
- Sjögren’s syndrome (Specific pattern).

Autoimmune ILD :
• NSIP pattern (M/c) :
- Systemic sclerosis.
- Anti-synthetase syndrome.
- Mixed connective tissue disease (MCTD).
- Sjögren’s syndrome (M/c pattern).
• UIP pattern :
Rheumatoid arthritis.

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 138 Medicine

----- Active space ----- Miscellaneous :

Inherited : Drugs :
• Neurofibromatosis - 1 (NF-1). Bleomycin.
• Tuberous sclerosis (TS).

Langerhans cell histiocytosis (LCH) :

• Features :
- Risk of pneumothorax. - Diabetes insipidus.
- Lung cysts. - Lytic bone lesions.
• Marker : CD1a.
• IHC : Birbeck granules (Tennis racquet appearance).

Lymphangioleiomyomatosis (LAM) :
• Seen in tuberous sclerosis. • Risk of pneumothorax.

om
l.c
Occupational lung diseases.

ai
gm
Note: @
56
Smoking associated ILD :
t4
hi

• DIP • LCH
c
ra

• RB-ILD • RA associated
al
raw
ag

Features 00:06:52
|
w
ro

• UIP > NSIP > COP.

ar
M

• ILD involves lower lobes >> upper lobe

©

Rheumatological Airway disorders : Pneumoconiosis : Miscellaneous :

disorders : • Allergic • Silicosis • LCH
• Sarcoidosis bronchopulmonary • Coal worker’s • Radiation-induced
• Ankylosing aspergillosis (ABPA) pneumoconiosis lung disease
spondylitis • HP • Berylliosis • Psoriasis (Rare)
Incidence :
• Middle age
• F > M..

Progression :
Type 1 respiratory Parenchymal involvement PaCo2↑ Pulmonary
failure Cor pulmonale.
FVC ↓ HTN

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 Restrictive Lung Diseases 139

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

Symptoms : Signs :
• Dyspnea on exertion/rest. • Clubbing.
• Dry cough. • Velcro crackles (Fine end inspiratory/
early expiratory.)

ILD vs Bronchiectasis :
ILD Bronchiectasis
Clubbing + -
Ribs crowding + -
Character Fine crackles Coarse crackles
Crackles Heard in expiration + -

om
Variation with position - +

l.c
ai
gm
Management 00:11:02
@
56
t4

PFT : ↓DLCO.
chi
ra
al

Chest x-ray : B/l, bibasal, reticulonodular infiltrates.

r aw
ag

HRCT: IOC.
|
w
ro
ar
M
©

CXR : ILD
Pattern HRCT findings
• Linear/reticular shadows (Septal thickening)
• GGOs (Sub-pleural)
UIP • Loss of lung architecture
• Honey combing Specific.
• Traction bronchiectasis
• Mild septal thickening
NSIP • Ground-glass opacities (GGOs) :
Postero-basal Specific
• Consolidation
COP • Reverse Halo sign : GGOs surrounded by
consolidation

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 140 Medicine

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

Dilated Septal
bronchi thickening Honeycombing Septal thickening GGO

UIP Pattern NSIP Pattern

om
l.c
ai
gm
COP : Reverse halo sign
Note : @
56
t4

Halo sign : Invasive aspergillosis.

chi
ra

Treatment :
al
aw

UIP :
r
ag

• Poor prognosis.
|
w

• Nintedanib.
ro
ar

NSIP :
M
©

• Steroids + mycophenolate mofetil (MMF).

• Scleroderma : Steroids avoided d/t risk of scleroderma renal crisis.
Conditions Causing Cysts & Nodules in Lungs :

LAM LCH LIP

Drug Induced ILD :
• Bleomycin. • Amiodarone.
• Busulfan. • Nitrofurantoin.
• Bromocriptine.

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 Restrictive Lung Diseases 141

Types of Pneumoconiosis 00:18:30 ----- Active space -----

1. Silicosis (M/c) 2. Coal worker’s 3. Asbestosis 4. Berylliosis :

pneumoconiosis • Ceramic industry/Batteries.
(CWP) • Features :
Acute : Chronic : - Non-caseating granulomas.
• Heavy exposure 10 - 30 yrs - Upper lobe ILD.
within 2 years. exposure. - D/d : Sarcoidosis.
• Symptoms :
Dyspnea. Note :
• CT : Crazy pavement Byssinosis H ypersensitivity pneumonitis
appearance. (Inhalation of organic dust).

Chronic Silicosis, CWP & Asbestosis 00:19:47

om
Radiological Findings :

l.c
ai
gm
Progressive massive fibrosis Egg shell calcification @
56
t4
chi
ra
al
raw
ag
|
w
ro

HRCT (Silicosis) CXR (Silicosis) Holly leaf sign (Asbestosis)

ar
M
©

Chronic Silicosis CWP Asbestosis

• Mining & quarry
Industry Coal Textile/shipping industry
• Slate industry
• Serpentine (90%) :
Chrysotile
Free silica/ • Amphibole (10%) :
Active moiety Coal dust
silicon dioxide (SiO2 ) - Crocidolite
- Amosite
(Most dangerous)

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 142 Medicine

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

Chronic Silicosis CWP Asbestosis

1. Pleural plaques with
calcification
(Classical finding) :
- Parietal pleura :
Holly leaf sign &
candle drip sign
- Visceral pleura :
Pleural involvement - Crowfeet sign
2. Benign asbestos related
pleural effusion (BAPE) :
- Earliest finding
- U/L hemorrhagic
(Exudative)
- Eosinophils < 25%

om
- Mesothelial cells < 50%

l.c
ai
• Nodule (Hallmark) :

gm
- B/L symmetrical @
56
- Conglomerate nodules
t4

(Multiple nodules
hi

joined together)
c

B/L lower lobe infiltrates

ra

Parenchymal • Cavitation ± • Nodules

al
aw

involvement • Hilar lymphadenopathy • Hilar lymphadenopathy -

Diffuse massive fibrosis
r
ag

• Egg-shell calcification
|

Progression
w
ro
ar

Progressive massive fibrosis

M

(Upper lobe ILD)

©

Risk of malignancy + (Minimal) - +

Upper lobe ILD + -
Affected cell Pulmonary alveolar macrophages (PAM) -
• Dyspnea • Dyspnea
Symptoms
• Chronic dry cough • Pleuritic chest pain
PFT Mixed pattern Restrictive pattern
• Reactivation of TB (Silico TB) Caplan’s syndrome :
Associations • Autoimmune conditions CWP + Rheumatoid arthritis -
(SLE, scleroderma, RA) (Active synovitis + ↑RF (Ig A))
Malignancy risk in asbestosis :
Ca Lung Mesothelioma
Years of exposure 10 - 30 years > 30 years
Smoking Additive effect No effect
Adenocarcinoma > SCC >
Type Epitheloid > Sarcomatoid
Small cell carcinoma
• Pleuritic chest pain with mass
Features Cough with hemoptysis
• Marker : Calretinin
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 ARDS, Pneumonia and Pleural Effusion 143

ARDS, PNEUMONIA & PLEURAL EFFUSION ----- Active space -----

Acute Respiratory Distress Syndrome (ARDS) 00:00:15

Etiopathogenesis :
• Sepsis Epithelial injury Inflammatory Endothelial damage
mediators
• Transfusion (Type 1 pneumocytes)
associated lung Fluid & protein
injury (TRALI) exudation
• Pancreatitis
Dyspnea Hypoxia

om
• Trauma

l.c
• Burns

ai
gm
New Berlin Criteria : 56
@
t4

Pulmonary edema Non-cardiogenic

chi
ra

Echocardiogram Normal
al
aw

B/L alveolar/interstitial infiltrates not explained by

Chest imaging
r
ag

effusion/collapse/nodules
|
w

Onset Acute Within 1 week of insult

ro
ar

PaO2/FiO2 ratio Mild : 200 - 300 Moderate : 100 - 200 Severe : < 100
M
©

Management :
Mechanical ventilation :
Prevention of Volutrauma ↓Tidal volume
Inverse ratio ventilation.
↑Frequency

Atelectotrauma : High PEEP.

Barotrauma : ↓Plateau pressure.

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 144 Medicine

----- Active space ----- Management of Pneumonia 00:05:12

CURB-65 Score :
C : Confusion.
U : BUN ≥ 21 mg/dL (Urea ≥ 42 mg/dL).
R : Respiratory rate > 30/min.
B : BP < 90/60 mm Hg.
65 : Age ≥ 65 years.

Rx :
• Outpatient management (Score 0) :
Risk factors/risk for resistance
- +

om
Amoxicillin 1 g TDS Amoxyclav 625 mg TDS

l.c
+ +

ai
gm
Azithromycin 500 mg OD Azithromycin 500 mg OD.
OR @
56

Doxycycline 100 mg BD.

t4
chi
ra

• Inpatient management :
al
aw

Score 1, 2 (Admit) Score 3 (ICU management)

r
ag

β-lactam + β-lactamase inhibitor

|
w

(Piperacillin + Tazobactam 4.5gm IV Q6H)

ro

First line
ar

+
M

Macrolide (Azithromycin 500 mg)

©

• Non-severe : Levofloxacin
Second line
• Severe : β-lactam + Fluoroquinolones

Response to therapy :
48 - 72 hrs No response Rule out Lung abscess (Necrotising pneumonia).
Empyema.
ARDS.

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 ARDS, Pneumonia and Pleural Effusion 145

Pleural Effusion 00:10:28 ----- Active space -----

Pleural Fluid :

70% : 25% : 1 - 5% :
Macrophages. Lymphocytes. Mesothelial cells
(Lining cells Secretes surfactant).
Detection :
Fluid Volume Detected By
10-20 mL (Normal) -
• USG
50 mL
• CXR lateral View
200 mL CXR PA View
300 mL Clinical examination

om
Pleural Effusion

l.c
Components :

ai
gm
• Glucose = Blood glucose. 56
@
• LDH < 50% of plasma LDH.
t4

• Protein : 1 - 1.5 g/dL.

chi
ra
al

Note :
r aw

Pleural fluid glucose < 30 mg/dL : RA.

ag
|
w

Exudative vs. Transudative Effusion :

ro
ar

Light’s criteria :
M

1. Pleural fluid protein/Serum protein ≥ 0.5.

©

2. Pleural fluid LDH/Serum LDH ≥ 0.6.

3. Pleural fluid LDH ≥ 2/3rd of upper limits of normal serum LDH

Any 1 + All 3 -

Exudative effusion : Transudative effusion :

Causes : Causes :
• TB. • Congestive cardiac failure
• Pneumonia. (On diuretics Exudative).
• Autoimmune disease • Cirrhosis.
(SLE). • Nephrotic syndrome.
• Malignancy. • SVC obstruction.
• Pancreatitis. • Myxedema/hypothyroidism.
• Hypoalbuminemia.
• Budd-Chiari syndrome.
• Constrictive pericarditis.
• Urinothorax.

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 146 Medicine

----- Active space ----- Pleural Effusion a/w Pneumonia :

Synpneumonic/Simple Complicated parapneumonic Empyema :

parapneumonic effusion : effusion : • Complicated parapneumonic
Seen in all pneumonia. • Bacterial invasion + fibrin effusion
+
+ septation. macroscopic pus.
• pH < 7.2. • Imaging :
• LDH↑↑ - X-Ray : D sign/Bottled out
• Protein↑↑ appearance.
• Gram stain + - CT : Split pleura sign.
• Rx : ICD.

om
l.c
ai
gm
@
56
t4
chi
ra
al
raw

D-sign Split pleura sign

ag
|

Conditions with Eosinophils in Pleural Fluid :

w
ro
ar

• Pulmonary infarction.
M

• Parasitic : Paragonimus westermani.

©

• Asbestosis.
Chylous vs. Pseudochylous Effusion :
Chylous Pseudochylous
Lymphatic rupture : Pleural thickening :
Cause • Trauma • TB
• Tumor • RA
• Triglycerides + • Cholesterol crystal +
Features • Chylomicrons + • Milky white fluid
• Milky white fluid

Drugs causing Pleural Effusion :

• Nitrofurantoin.
• Dantrolene.
• Methysergide.
• Bromocriptine.
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 Cortical and Subcortical Lesions 147

CORTICAL AND SUBCORTICAL LESIONS ----- Active space -----

Frontal Lobe Lesions 00:02:57

Areas Functions Lesions

• 30% Motor fibres of corticospinal tract
Precentral gyrus :
• Pyramidal cells of Betz : C/L UMN weakness :
1o Motor cortex
Lowest threshold for activation Face & upper limbs
(Area 4)
• Initiates voluntary activity : Fine & discrete
• 30% Motor fibres
Premotor & supplementary • Preparation of movement :
• Spasticity : Hypertonia
Motor cortex - Tone - Inhibition of

om
• Primitive reflexes +
(Area 6 & 8) - Posture antagonists

l.c
- Muscle alignment

ai
gm
Inferior frontal gyrus : Broca’s (Motor/Non-fluent) aphasia :
Broca’s area Motor speech @ • Dysarthric • Sparse
56

(Left/Dominant lobe lesion) • Effortful • Prosody lost

t4
hi

Frontal Eye Field (FEF) C/L gaze : Component of horizontal gaze pathway Gaze fixed towards side of lesion
c
ra
al

Prefrontal cortex : • Energization & motivation

aw

• Dorso-lateral • Execution
r
ag

• Orbital • Behaviour : • Abulia Severe Akinetic mutism

|

- Judgement - Fluency • Picks disease/fronto-temporal

w
ro

- Insight - Abstract dementia : Degenerative

ar

- Personality thinking
M

• Theory of mind (Sympathy & empathy)

©

Note : : FEF

Lesions of horizontal gaze pathway :

• Internuclear ophthalmoplegia : MLF lesion
- I/L Adduction weakness. Midbrain
- C/L Abduction nystagmus.
• One and half syndrome : PPRF + MLF lesion
- I/L Abduction.
- I/L Adduction. Lost.
- C/L Adduction. Pons

- C/L Abduction intact.

Horizontal gaze pathway
PPRF : Paramedian pontine reticular formation
MLF : Medial longitudinal fasciculus

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 148 Medicine

----- Active space ----- Parietal Lobe Lesions 00:21:10

Dominant Lobe Lesions :

Areas Functions Lesions
• 40% Motor fibres of CST
• Cortical sensations :
Post central gyrus : • C/L UMN weakness (Tone &
- Tactile localisation
1o Sensory cortex Primitive reflexes not involved)
- Tactile/2 point discrimination
(Area 3, 1, 2) • Loss of cortical sensations
- Stereognosis
- Graphesthesia
Generate praxicons : sensory
Superior parietal lobule Apraxia : Ideational & ideomotor (M/c)
guidance for movement
Visual agnosia (Contributed by
End of sylvian fissure :
Gnosis parieto-occipito & Temporo-occipital
Supramarginal gyrus
association areas)

om
Inferior • Reading + writing Gerstmann’s syndrome :

l.c
parietal • Naming • Alexia + agraphia

ai
gm
lobule End of superior temporal • Spatial orientation : • Anomia/Nominal aphasia
sulcus : Angular gyrus - Fingers @ • Finger anomia
56

- Numbers • Acalculia
t4
hi

- Direction • Right & left disorientation

c
ra
al
aw

Note :
r
ag

Alexia without agraphia : Lesion of splenium of corpus callosum (PCA infarct).

|
w
ro

Non-dominant Lobe Lesions :

ar
M

• Visuospatial disorientation.
©

• Constructional apraxia.
• Dressing apraxia.
• Topographical agnosia.
• Hemispatial neglect/anosognosia :
Lobe Extrapersonal space side Lesion
Right Right + left Left side neglect
Left Right No effect

Dominant/Non-dominant Lobe Lesions :

Inferior Homonymous quadrantanopia.

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 Cortical and Subcortical Lesions 149

Temporal Lobe Lesions 00:33:25 ----- Active space -----

Superolateral Surface :
Temporal : Superior homonymous quadrantanopia.
Areas Lesions
Auditory cortex (Area 41, 42) -
Auditory connection fibres (To wernicke’s area) Pure word deafness
Auditory association areas Auditory agnosia
Wernicke’s area Sensory/fluent aphasia
Temporo-occipital association fibres Visual agnosia

Note :
• Motor aphasias.
• Sensory aphasias.

om
l.c
ai
Repetition

gm
+ @ -
56

• Broca’s aphasia
t4

• Transcortical motor aphasia

hi

+ • Conduction aphasia
c

Comprehension • Nominal aphasia

ra

(Arcuate fasciculus lesion)

al
aw

Isolation aphasia/Echolalia • Global aphasia

•
r

-
ag

• Transcortical sensory aphasia • Wernicke’s aphasia

|
w
ro
ar
M

Medial Surface :
©

Areas Functions Lesions

Kluver Bucy syndrome :
• Hippocampus (H) • Homeostasis
B/L medial temporal lobe/limbic cortex lesion
• Parahippocampus (P) • Olfaction
• Hyperorality
• Fusiform Gyrus (F) • Episodic short term memory
• Loss of fear/aggressiveness
• Inferior temporal gyrus (ITG) • Emotion
• Hypersexuality
• Superior temporal gyrus (STG) • Sexuality
• Visual inattention

STG

ITG H

F P
Arrangement on medial surface

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 150 Medicine

----- Active space ----- Occipital Lobe Lesions 00:38:00

Areas Lesions
Visual cortex C/L congruous homonymous hemianopia with macular sparing
Occipital association areas Colour agnosia
• Anton’s syndrome : Cortical blindness
• Balint’s syndrome :
B/L occipital lobe - Optic ataxia
- Oculomotor apraxia
- Simultagnosia

Dementia 00:40:05

Criteria :
Major cognitive impairment + ≥ 1/6 cognitive domains.

om
l.c
Cognitive domains Areas

ai
gm
Memory Medial temporal lobe (Hippocampus)
@
Language Broca’s (IFG)/Wernicke’s (STG)
56
t4

Executive function
chi

Complex attention Prefrontal cortex

ra
al

Social cognition
raw

Perceptual motor/Praxicon Superior parietal lobule

ag
|
w

Etiology :
ro
ar

• Alzheimer’s dementia (M/c) : Cortical dementia.

M
©

• Diffuse Lewy body (DLB) dementia.

• Vascular dementia Post CVA/Multi-infarct state
Binswanger’s disease
Subcortical dementia.
(White matter disease)
• Normal pressure hydrocephalus (NPH).
• Progressive supranuclear palsy (PSP).

Reversible dementia : 10%.

• Drugs : Benzodiazepines, Lithium.
• Endocrine : Hypothyroidism.
• Metabolic : Vit. B12, Cu2+, Vit. E deficiency.
• Ear abnormalities.
• �PH.
• Trauma/tumors.
• Infections : Chronic meningoencephalitis.
• Anemia.
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 Cortical and Subcortical Lesions 151

Young onset dementia : 50 - 60 years. ----- Active space -----

• Picks disease/FTD
Rapidly progressive
• DLB dementia
(Infections : Whipple’s, HIV).
• Prion disease : Creutzfeldt-Jakob disease
• Huntington’s disease.

Alzheimer’s Disease (AD) 00:47:40

• AKA Type 3/brain diabetes mellitus.

• Tauopathy : Hyperphosphorylated tau protein deposits.

Occurrence :

Sporadic : Apo E4. > Familial : Young onset

om
• Chr. 14 : Presenilin 1.

l.c
ai
• Chr. 1 : Presenilin 2.
gm
@
Pathophysiology :
56
t4

Chromosome 21 : Amyloid precursor protein gene Metabolic syndrome

hi
c

(Hyperinsulinemia/
ra
al

α Secretase β Secretase pathway Insulin resistance)

aw

pathway
r
ag

N ↑Aβ amyloid ↓Insulin degrading enzyme

|
w
ro

Aβ 40 Aβ 42
ar
M
©

Cerebral amyloid angiopathy AD

(CAA).
Amyloid deposits
Outside neuron Inside neuron

Neuritic plaques Neurofibrillary tangles

↑Inflammation Mitochondrial injury
Gliosis. Damages neurons.

Atrophy of :
• Medial temporal lobe.
• Lateral temporal lobe.
• Cingulate gyrus.
• Entorhinal cortex.

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 152 Medicine

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

Stage III :
• Visuo-spatial disorientation
Stage IV : Parietal
• Apraxias
Behavioral/ Prefrontal lobe
Execution abnormalities cortex
Angular gyrus Stage II : Gerstmann
syndrome
Medial temporal
lobe

Stage I : Episodic memory loss

Management :
Cholinesterase inhibitors :

om
• Rivastigmine.

l.c
ai
• Donepezil.
gm
• Galantamine. @
56
t4

NMDA antagonist : Memantine.

chi
ra
al

Other Dementias 00:55:25

raw
ag

Young Onset & Rapidly Progressive Dementias :

|
w
ro

Pathogenesis Presentations
ar

• Prefrontal cortex : Behavioural

M
©

Fronto-temporal • Sporadic (70%) : MAPT gene (Chr 17) & executional abnormalities
dementia/ • Proteins TDP 43 (M/c) • Limbic cortex (Temporal) :
Picks disease Tau (AKA taupathy) - Hyperphagia
- Hypersexuality
• Early symptoms :
- REM sleep disorder
- ANS manifestations
Diffuse lewy body • Dementia
AKA α synucleinopathy (Also MSA) • B/L axial rigidity : Rocket sign
dementia
• Visual hallucinations +
Fluctuating alertness
(Aggravated with anti-psychotics)
• Dementia
Prion disease : • Myoclonus
• β pleated PrPsc protein (Infectious)
Creutzfeldt • Long incubation period
• - Immune response
Jakob disease • Cortex ribboning
• Dx : Brain biopsy

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 Cortical and Subcortical Lesions 153

Cortical vs. Subcortical Dementia : ----- Active space -----

Cortical Subcortical
• AD • DLB
• FTD • PSP
Etiology
• CJD • NPH
• Multi-infarct • Binswanger’s disease
Gray matter : White matter :
Areas affected Cortex • Basal ganglia • Corticospinal tract
• Thalamus • Corticobulbar tract
C/f Memory + Cortical abnormalities Extrapyramidal manifestations
Mood disorders + : Apathy +

Vascular Dementia :
Multi-infarct state/post CVA :

om
• B/L PCA.

l.c
ai
• Step-ladder cognition decline.
gm
@
56
Binswanger’s disease :
t4
hi

• Disease of white matter.

c
ra

• Lacunar/lipohyalinotic infarcts (Vessel size : 30 - 300 μm).

al
aw

• Clinical presentations :
r
ag

- Prolonged hypertension.
|
w

- Abnormal gait (Recurrent falls) :

ro
ar

Gait apraxia (Magnetic/Ignition foot phenomenon).

M

- Pseudobulbar palsy.
©

- Urinary abnormalities.
Normal Pressure Hydrocephalus (NPH) :
• Communicating type.
• Non-obstructive.
• Pathology : ↓CSF absorption.
• Idiopathic (M/c).
• Ventriculomegaly.
• C/f :
- Gait apraxia.
- Urinary incontinence.
- Dementia (Subcortical).

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 154 Medicine

----- Active space ----- Subcortex 01:10:04

Subcortex

Grey matter : White matter :

Basal ganglia/Islands of nuclei : Tracts through internal capsule
• Caudate nucleus Corpus striatum
Lentiform • Putamen
Corticospinal. Corticobulbar.
nucleus • Globus pallidus
• Subthalamic nuclei.
• Substantia nigra.

Role of basal ganglia (BG) :

• Planning & coordination of complex
motor activity BG Hyperkinetic disorders.

om
• Intensity & scaling of movements disorders Hypokinetic disorders :

l.c
• Cognitive aspect of movements

ai
Akinesia/ bradykinesia
gm
@ (Paucity in movement).
56
t4
hi
c

Parkinson’s Disease
ra

01:15:04
al
r aw

Akinetic disorders
ag

80% 20%
|
w
ro

Idiopathic Parkinson’s Atypical Parkinson’s/

ar

Parkinson’s plus syndrome.

M

80% 20%
©

Classical/ Akinetic rigid syndrome :

tremor predominant. Poor prognosis.

Onset :
Elderly (> 70 y) : Young onset :
Sporadic. Genes involved :
• PARK 1 : α-synuclein.
• PARK 2 : Parkin.
2° Parkinson’s :
• Wilson’s disease.
• Drug induced (Rx : Centrally acting anticholinergic).
• Mn2+ toxicity.

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 Cortical and Subcortical Lesions 155

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

α-synucleinopathy :
• REM sleep disorders 5 - 10y before disease onset.
• ANS symptoms
• Tremors
• Rigidity 2 - 3 yrs • Postural instability
• Gait abnormalities Dementia.
• Akinesia
• Postural Swallow tail sign :
instability 5 - 10 yrs Absent in PD

PD tremor vs. essential tremor :

Parkinson’s tremor (AKA pillrolling tremor) Essential tremor

om
Frequency 4 - 6 Hz : Fine 5 - 12 Hz

l.c
Resting tremor

ai
gm
Characteristics Disappears with movement Postural
@
Reappears 5 - 20 s after posture
56
t4

Distribution Upper limb Axial (Head) + Upper limb

chi

Writing Micrographia Large & tremulous

ra
al

Response to β-blockers - Good

r aw
ag

Rigidity :
|
w
ro

• Length & velocity independent.

ar

• Present on agonistic & antagonistic movements.

M
©

• Types :
- Cogwheel (Wrist) : Tremor + rigidity.
- Lead pipe (Elbow).

Akinesia :
• Bradyphrenia : Paucity in thoughts.
• Flexion hypertonia : Stooped posture.
• Festinant gait : Short, shuffling.
• ↓Arm swing.
• Micrographia.
• Hypomimia.
Akinesia in Parkinson’s disease

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 156 Medicine

----- Active space ----- Parkinson’s Plus Syndrome 01:23:30

Atypical Parkinson’s/Parkinson’s plus

Progressive supranuclear Corticobasal Multisystem Diffuse Lewy

palsy (PSP) : M/c degeneration atrophy body dementia

Taupathies. α-synucleinopathies.

Presentation :
• Unresponsive to L-dopa Common to
• Absence of tremor at presentation atypical PD.
PSP : Morning glory sign
Progressive supranuclear palsy :
• B/L axial rigidity (Rocket sign + ).

om
• Recurrent falls : Extension hypertonia

l.c
ai
+ wide-based gait.

gm
• Supranuclear downgaze palsy. 56
@
• Dementia.
t4
chi

Multisystem atrophy :
ra
al

• Type A : S hy-Drager syndrome PSP : Hummingbird/penguin sign

raw

(ANS symptoms predominant).

ag
|

• Type C : Cerebellar predominant.

w
ro

• Type P : Parkinson predominant.

ar
M

- B/L axial rigidity.

©

- Craniocervical dystonia :
Pisa sign.
Diffuse Lewy body dementia :
• Dementia predominant. PSP : Procerus sign MSA : Hot cross bun sign
• Visual hallucinations. (↑Wrinkling)
• Fluctuating alertness.

Corticobasal degeneration :
• Alien limb phenomenon/
limb apraxia.
• Myoclonus.
• Cortical deficit.
• Extrapyramidal
effects.
Lewy body in DLB MSA : Pisa sign
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 Neuropathies 157

NEUROPATHIES ----- Active space -----

LMN 00:00:06

Composition :
Nerves originating from/terminating at :

Anterior horn cells (AHC) : Cranial nerve nuclei :

• Ventral horn of grey matter • Midbrain : 3, 4.
of spinal cord • Pons : 5, 6, 7, 8.
• Contains α & γ motor neurons • Medulla : 9, 10, 11, 12.

om
l.c
ai
gm
@
56
t4
chi
ra

Pathologies :
al
aw

Site of lesions
r
ag
|

Purely sensory Sensory - motor Pure motor

w
ro
ar

Ganglion :
M

Root : Plexus : Nerve : AHC NMJ Muscle

©

Ganglionopathy
Radiculopathy Plexopathy Neuropathy

Radiculopathy, Plexopathy & Ganglionopathy 00:03:47

Radiculopathy vs Plexopathy :
Radiculopathy Plexopathy
• Compressive : Intervertebral disc prolapse
Etiology • Non-compressive polyradiculopathy : Tumor compression
Guillain-Barre syndrome
• Asymmetrical
• Asymmetrical
Involvement • Motor : Proximal & distal
• Sensory & motor
• Sensory : +
• Root pain :
Pain :
- Along distribution of nerve root
• Continuous & severe
Presentation - Brief electric shock like pain
• Deep seated
• Weakness along nerve root
• Dull aching
• Loss of deep tendon reflexes
Paraspinal denervation + -
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 158 Medicine

----- Active space ----- Ganglionopathy :

Large fibres symptoms : Severe sensory truncal ataxia.
Etiology :
• Sjögren’s syndrome.
• Anti-Hu paraneoplastic syndrome.

Types of Neuropathies 00:09:35

Based on The Number of Nerves Involved :

Mononeuropathy Polyneuropathy

om
Carpal tunnel syndrome : Mononeuritis multiplex :

l.c
• Median nerve involved. • Leprosy (M/c).

ai
• Can be a/w amyloidosis. • PAN.

gm
• Cryoglobulinemia.
@
56
Based on Size of Nerves :
t4
chi
ra
al

Large fibre Small fibre Combined large + small fibres :

aw

neuropathy neuropathy • Vincristine

r
ag

• Carcinomatous involvement
|
w

Large vs small fibre neuropathy :

ro
ar
M

Symptoms
©

Etiology Tracts affected Sensations affected

+ve -ve
• Taxanes
• Fine touch • Numbness
• Pyridoxine toxicity
• Proprioception • Tingling • Paresthesia
Large • Vitamin B12 deficiency
Posterior column • Position sense • Cotton wool • Sensory ataxia:
fibres • Vitamin E deficiency
• Joint sense sensation Romberg’s test
• Copper deficiency
• Vibration +ve
• Friedreich ataxia
+ve -ve
Loss of sensation :
• DM
Burning pain Burns/non healing
• Vasculitis
ulcers
• Amyloidosis
• Pain • Chronic
Small • Leprosy Spinothalamic
• Temperature • ANS symptoms +
fibres • HIV tract
• Pressure • Distal to proximal
• Uremia
• Fabry’s disease • Longer axons more affected
• Tangier’s disease • Stocking & glove pattern
• Sensory >> Motor
• Reflex : Preserved (± Ankle-jerk)
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 Neuropathies 159

Based on Pathology : ----- Active space -----

Demyelinating : Axonal :
• Most acute neuropathies : AIDP • Most chronic neuropathies
• CIDP • Most drug induced neuropathies
• Carpal tunnel syndrome • Acute intermittent porphyria
• Refsum’s disease • Charcot marie tooth disease.
• Charcot Marie tooth disease
• Drugs :
- Amiodarone
- Chloroquine
- Gold.
Note :
Neuropathies with severe ANS symptoms :
• DM > Amyloid > Porphyria. • Fabry’s disease.

om
• HIV. • Vincristine.

l.c
ai
gm
Types 56
@ 00:23:45
t4

Based on Etiology :
chi

Inherited neuropathies :
ra
al

• Charcot Marie tooth disease : Type 1 (AD).

aw

Demyelinating diseases
r

• Refsum’s disease : α oxidation defect.

ag
|

• Familial amyloid polyneuropathy :

w
ro

- Small fibre neuropathy. - ↑↑Autonomic findings.

ar
M

- Sensory > Motor. - Painful.

©

• Porphyria (Axonal).
• Tangiers disease :
- Orange stones. - ABC cassette protein defect.
Acquired neuropathies :
Large fibre disease Small fibre disease
• Vitamin B12 deficiency • DM • Uremia
Seen in • Vitamin E deficiency • Vasculitis
• Copper deficiency • Leprosy
+ Symptoms - Symptoms
• Numbness
Presentation • Tingling • Dysesthesia Stocking & glove pattern
• Cotton wool sensation • Paresthesia
• Woody rubbery sensation • Sensory ataxia
• Romberg’s +ve
Reflex Absent Preserved (Except ankle jerk)
Involvement More motor involvement Minimal motor involvement
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 160 Medicine

----- Active space ----- Charcot Marie Tooth Disease : Type 1 00:27:08

Presentation :
Long & slow progressive demyelinating neuropathy.
• Foot deformities : • Kyphoscoliosis.
- Pes cavus. • Palpable nerves.
- Hammer toes.
- Foot drop.
• No sensory symptoms but large fibre sensory signs + .
• Distant >> proximal weakness : ‘Inverted champagne bottle’ legs.
Ix :
Nerve conduction studies : Uniformly ↓conduction velocity.
Biopsy : Onion bulbs.

om
l.c
ai
gm
@
56
t4
chi

Foot deformity Inverted champagne Biopsy : Onion bulbs

ra
al

bottle appearance
raw
ag

Guillain-Barre Syndrome (GBS) 00:30:22

|
w
ro

• Demography : 40 yrs, Male > Female.

ar
M

• Acute : < 4 weeks.

©

• Demyelinating : Anti-GM1 Ab (Ab against myelin).

+
• Inflammatory : Complement cascade.
• Polyradiculoneuropathy.
Variants :

Axonal Demyelinating
(↓Survival rates)
Miller Fisher syndrome :
AMAN : AMSAN : • Anti-Gq1b Ab.
Acute motor • Acute sensorimotor • Presentation :
axonal neuropathy. axonal neuropathy. - Ophthalmoplegia.
• Anti-GD1a Ab. - Areflexia.
- Ataxia.
- ± Bickerstaff encephalitis.

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 Neuropathies 161

Pathogenesis : ----- Active space -----

Preceding infection with Campylobacter jejuni Molecular mimicry.
• B/L lower limb sensory symptoms (large fibres)
• Transient bowel & bladder issues
24-48 hrs
Weakness : Polyradiculopathy
• Proximal & distal muscles.
• Atonic, areflexic paraparesis.
Progression : Lower limbs Upper limbs Cranial nerves (VII) Respiratory involvement.
Poor prognosis

Autonomic instability :
• Postural hypotension. • PRES (Posterior reversible
• Tachy-brady arrhythmias. encephalopathy syndrome).

om
l.c
ai
Management :

gm
Investigations : @
56

• Nerve conduction studies : ↓Conduction velocity.

t4
hi

• Lumbar puncture : Albuminocytological dissociation.

c
ra
al
aw

AIDP vs CIDP :
r
ag
|

CIDP AIDP
w
ro

Onset > 8 weeks < 4 weeks

ar

70% : Preceding injection

M
©

• Upper respiratory infection

Recent history 30% : Preceding infection
• Diarrhea
• Dysentery
Autonomic symptoms - +
Involvement Sensory + Motor Sensory
Weakness Distal to proximal Proximal & distal
Cranial nerve involvement 10% 30%
• Steroids (DOC)
• Resistant : • IVIG
Rx
Plasma exchange therapy • Plasmapheresis (PLEX)

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 162

----- Active space ----- HEADACHE AND SEIZURES

Pain sensitive structures :

• Dural venous sinuses.
• Dura around vessels. • Dural arteries (Meningeal arteries).
• Small cerebral vessels. • Pia mater.
Pain insensitive structures :
• Choroid plexus.
• Ependyma.

om
Headache 00:00:55

l.c
ai
Classification :
gm
Features @ Causes
56
t4

• Tension headache (M/c 1˚) Cluster headache (M/c)

chi

• Benign • Migraine (2nd M/c 1˚)

ra

Paroxysmal hemicrania
al

• Recurrent • Trigeminal autonomic cephalgias (TACs) :

aw

Primary
• No organic SUNCT
r
ag

cause
Hemicrania continua
|
w
ro

Secondary - Systemic infections

ar
M

Dangerous Headache :
©

1. New onset headache in > 50 yrs 2. ↑Intracranial tension :

(F > M) : • Subacute
• Seen in giant cell arteritis • Rapidly progressive Examine fundus
• Associated with : • Nocturnal awakening If papilledema +
- Scalp tenderness • Vomiting : Relieve headache (Surest sign)
• ↑Intensity by bending/coughing : Imaging.
- Thick/nodular vessels
- Jaw claudication Seen in meningeal inflammation.
- ESR↑.
Signs of ↑ICT :
• Bradycardia. • Hypertension.
• Bradypnoea. • Cardiac arrhythmia.
• VI CN palsy (False localizing sign).
Complication : Herniation Coning.
• M/c Site : Uncus (Inferior part of temporal lobe).
• Signs : 3rd nerve palsy (Pupil involved).
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 Headache and Seizures 163

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

CN VI palsy

Herniation Papilledema

Ix :
↑ICT

om
l.c
MRI : R/o space MRA MRV : R/o CVT

ai
gm
occupying lesion (SOL)
@
56
t4
hi

If normal
c
ra
al
aw

Benign intracranial HTN : 1˚ empty sella

r
ag

(Rx : Acetazolamide/topiramate Drain out CSF). Empty sella

|
w
ro
ar
M

Tension Type Headache and Migraine 00:08:15

©

Tension Type Headache :

• F > M (Middle aged).
• A/w depression in 1/3rd cases (Prophylaxis : Amitriptyline).
• Holocranial band like sensation (Does not affect daily living activities).

Migraine :
Features :
• F > M. • Episodic.
• Adolescent onset. • Severity ∝ age.
Types :
1. Classical (20%) : With visual aura.
2. Common (80%) : Not a/w aura.

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 164 Medicine

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

Natural history :
1-2 days before episode : Duration : 4-72 hrs Post-headache phase (1-2 days) :
Restless & irritable Episode : Lethargy

a. Aura (Visual) : b. Headache :

Bright, zig-zag lines • Throbbing/pounding/pulsatile/episodic :
(Fortification spectra). Frontotemporal (U/L B/L).
• A/w photophobia & phonophobia.
• Nausea + .
• Vomiting + / - .
Mx :

Mild to moderate : Moderate to severe : Severe to very severe :

• NSAIDS 5-HTIB/ID agonist (Triptans) : 6 mg S/C Sumatriptan

om
• Antiemetics. C/I : (Intranasal preparations + ).

l.c
• CVA.

ai
• CAD.

gm
• Uncontrolled HTN.
@
56
• Brainstem aura.
t4

• MAO - use.
chi

• Newer drugs :
ra
al

- Erenumab ( - CGRP receptor).

raw
ag

- Ditans (5-HTIF agonists).

|

• Prophylaxis :
w
ro
ar
M

Class I : Class II : Class III :

©

• Propranolol • Venlafaxine • Pizotifen (5HT2

• Valproate • TCA. antagonist)
• Topiramate • Flunarizine (CCB)
• Clonidine
(S/E : ↑Renal • Candesartan.
stones, weight loss).

Trigeminal Autonomic Cephalgias 00:18:33

General C/F :
• Unilateral Conjunctival congestion/lacrimation
• Very severe + I/L ANS symptoms Eyelid edema
• Short lasting Nasal congestion/rhinorrhea
• Neuralgic.

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 Headache and Seizures 165

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

Paroxysmal Hemicrania
Cluster headache (M/c) SUNCT
hemicrania continua
Gender M>F - - F > M (Elderly)
15 mins - 3 hrs 2 - 30 5 - 240
Duration of attack -
(1 - 5 attacks/day) minutes seconds
Paroxysmal
Stabbing pain in
attacks with
Features periorbital region - -
U/L continuous
(Clusters)
headache
Alcohol trigger + - - -
+ (No

om
Cutaneous trigger - - refractory -

l.c
ai
period)
gm
Migrainous features + @ - + -
56
t4

Nocturnal headache + - - -
chi

• 100 % O2 (Best) : 12 - 15
ra
al
aw

Rx L/min for 10 - 20 mins - - -

r
ag

• S/C Sumatriptan
|

• Short term : Steroids

w
ro

Prophylaxis • Long term : Verapamil > Indomethacin Lamotrigine Indomethacin

ar
M

Topiramate
©

Trigeminal Neuralgia 00:26:00

F > M (50 - 60 yrs).

C/F :
• Electric shock like pain (Brief) : Along • No sensory signs.
CN V2 and V3. • Cutaneous trigger + Refractory
• Tic douloureux : Wince with pain. period + .
Causes :
• U/L : Compression (M/c : Superior cerebellar artery).
• B/L : Demyelination (Eg : Multiple sclerosis).
Rx :
• DOC : Carbamazepine > Lamotrigine (Check for HLA B1502 : Risk of Stevens
Johnson syndrome).
• If not responsive Microvascular decompression.

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 166 Medicine

----- Active space ----- Seizure : Focal 00:28:58

ILAE classification (2025) :

Focal Generalized : Unknown

• Absent seizures.
Impaired • Myoclonic GTCS
Preserved
consciousness consciousness • GTCS.
(LOC + ) (LOC - )
Focal :
Impaired consciousness Preserved consciousness
Previously called Complex partial seizures Simple partial seizures

om
• Behavioural arrest
• Todd’s palsy

l.c
• Aura (Abdominal)

ai
• Jacksonian march

gm
Presentation • Automatisms (Lipsmacking,
@ • Epilepsia partialis
chewing)
56
continua
t4

• Anterograde amnesia
chi

• M/c : C/L face and

ra
al
aw

U/L involved (D/t 2˚

r
ag

pathology : SOL in brain)

|

Hippocampal sclerosis • Motor >>> Sensory :

w

Features
ro

(Medial temporal lobe epilepsy) - Atonic

ar
M

- Tonic
©

- Clonic
- Myoclonic
Ix EEG : Temporal spikes MRI
Carbamazepine (DOC) >
Rx Lamotrigine (SJS), Levetiracetam -
(Risk of suicidal ideations)
Note :
Oxcarbazepine :
• ↓S/E compared to Carbamazepine.
• ↑Risk of : SIADH, hyponatremia.

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 Headache and Seizures 167

Generalized Seizure 00:38:01 ----- Active space -----

Rx : Valproate > Topiramate (or) Lamotrigine (↓Teratogenic risk : 2 - 3.4%).

Absent Seizure :
• Seen in child (< 12 yrs).
• Part of epileptiform syndrome.

Presentation :
• Transient LOC (No postural loss) : • IQ : Normal.
Stare. • Trigger : Hyperventilation.
• No movements (Except : eyelids).
Ix :
EEG : 3 Hz spike and wave pattern.

om
l.c
ai
GTCS :

gm
@
56
t4

Myoclonic GTCS : GTCS :

chi

Juvenile myoclonic epilepsy Cause :

ra
al

• Adolescent (F > M) • Metabolic :

aw

• Transient LOC - ↓Glucose - ↓Ca2+

r
ag

• Trigger : Sleep deprivation - ↓Na+ - ↓Mg2+

|

• DOC : Valproate. • Uremia (CKD)/hepatic

w
ro

encephalopathy (CLD)
ar

• Encephalitis/sepsis
M

• Paraneoplastic
©

• Autoimmune (Anti NMDA

antibodies)
• Drugs :
- Theophylline - Imipenem
- TCA.

Status Epilepticus (SE) 00:46:44

Continuous seizure ≥ 5 minutes (or) ≥ 2 seizure events (No consciousness in b/w).

Timeline for Rx :

5 min (T1) : 30 min (T2) : Target 1 hr : Max time limit

Ideal. (Medical Mx). (> 1 hr Irreversible
brain damage).

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 168 Medicine

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

Causes :
• Viral (M/c)
New onset refractory status
• Autoimmune (Anti NMDA antibodies)
epilepticus (NORSE).
• Paraneoplastic

Rx :
2 IV lines

Lorazepam : 0.1 mg/kg Phenytoin : 15 - 20 mg/kg

(Max : 4 mg) (or)
(or) Phosphenytoin
Midazolam (or)
(or) Valproate : 30 - 40 mg/kg

om
Diazepam. (or)

l.c
Levitiracetam : 30 - 40 mg/kg.

ai
gm
Non-convulsive SE : @
56

• Altered sensorium ± minor motor phenomenon.

t4
hi

• Continuous EEG monitoring needed.

c
ra
al
raw
ag
|
w
ro
ar
M
©

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 Approach to Stroke 169

APPROACH TO STROKE ----- Active space -----

Blood Supply of Brain :

A2
Anterior cerebral arteries
Anterior communicating artery
A1
Ophthalmic artery
Middle cerebral artery
Anterior choroidal artery
Internal carotid arteries
Posterior communicating arteries
P1 P2
Posterior cerebral arteries

om
Superior cerebellar artery

l.c
ai
Pontine arteries

gm
Basilar artery
@
Labyrinthine artery
56
t4

Anterior inferior cerebellar artery (AICA)

chi
ra
al

Vertebral artery
aw

Posterior spinal artery

r
ag

Anterior spinal artery

|
w

Posterior inferior cerebellar artery (PICA)

ro
ar
M
©

: Terminal branches of ICA (Mnemonic : OPAAM)

Surfaces of Brain :
Blood supply Lesion
• C/L UMN hemiplegia (Predominant : Face and arm)
Superolateral MCA (Major) • Macula involvement
• Cortical findings
• Lower limb weakness
Medial ACA (A2 ) • Urinary incontinence (Paracentral lobule involved)
• Apathy (Medial prefrontal cortex involved)
PCA C/L congruent homonymous hemianopia
Inferior
(Temporal pole : MCA) (Spares macula)

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 170 Medicine

----- Active space ----- Subcortex :

Grey matter : White matter :

Island of nuclei Internal capsule (IC) :
(Basal ganglia) • Densely arranged
• Corticobulbar fibers : Genu
• CST : Anterior 2/3rd of posterior limb

Blood supply of IC :
Anterior limb Genu Posterior limb Retrolentiform Sublentiform
Upper MCA : M1 Lenticulostriate artery
ACA : Recurrent branch ICA Anterior Anterior choroidal artery
Lower
(Heubner’s artery) (Partly : PCOM) choroidal artery

om
l.c
MCA Lesion

ai
00:13:27

gm
@
56
• Superolateral surface involved
t4
hi

• C/L hemiplegia
c
ra

• Global aphasia
al

• Weakness
aw

M2 - Superior
• Broca’s aphasia
r

• C/L hemiplegia
ag

• Massive stroke (Cortex M1 M2

|
w

& subcortical findings) (Horizontal sulcus) (Sylvian fissure)

ro
ar
M
©

Wernicke’s aphasia
Lenticulostriate M2 - Inferior
(No weakness)

• C/L dense hemiplegia (UL = LL)

• Homonymous hemianopia
• Hemi anaesthesia (Hemisensory loss)
• C/L UMN 7th nerve palsy

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 Approach to Stroke 171

PCA and ACA Lesions 00:18:55 ----- Active space -----

PCA :

B/L lesion
P1 P2

Midbrain Subthalamus Thalamus • Anton syndrome :

Lesions Cortical blindness
• Balint syndrome:
Dejerine Roussy syndrome : Artery of Percheron lesion : - Optic ataxia
• Involves thalamogeniculate artery • Anatomical variation - Oculomotor apraxia
• C/f : C/L burning pain (UL and LL) • Triad : - Simultagnosia
- Drowsiness - Palinopsia
- Gaze palsy

om
- Memory loss

l.c
ai
gm
Medial temporal lobe
56
@ Occipital lobe
Lesions Lesion
t4

C/L congruent macular

hi

Splenium : Association areas : Hippocampus : sparing hemianopia

c
ra

Alexia without agraphia Agnosia Memory issues

al
r aw

Note :
ag
|

Alexia with agraphia : Seen in Gerstmann syndrome.

w
ro
ar

ACA :
M
©

A1 A2

Medial surface of brain

Caudate nucleus Anterior IC
(Antero-inferior) hypothalamus (Anteror limb)

Lesions : No symptoms

Stroke and TIA 00:24:50

Stroke :
• Abrupt onset.
• Focal/global neurological deficit.
• Lasting ≥24 hrs (Vascular origin).

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 172 Medicine

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

TIA :
Lasting < 1 hr
Episode of neurological deficit Diffusion weighted MRI
(D/t focal brain/retinal ischemia)
Hyperintense lesion : Normal :
Minor stroke TIA
Dual antiplatelet therapy

Classification of Stroke :

Ischemic (85%) Hemorrhagic (15%)

om
Thrombotic Embolic

l.c
ai
gm
Artery-artery (M/c) Cardioembolic
@
56

Thrombotic vs. embolic :

t4
chi
ra

Thrombotic Embolic
al
aw

Onset Evolving Hyperacute

r
ag

Weakness ↑Over 48-72 hrs Full at onset

|

Lesions Single Multiple

w
ro

Thrombectomy Useful -
ar
M

Good recovery - +
©

Seizure - +
Hemorrhagic transformation - +

Management of Stroke 00:29:25

Goals :
• Recanalization/reperfusion.
• Prevent 2° brain damage :
- Hemorrhagic transformation.
- ↑ICP.
- SIADH/hyponatremia.
• Optimize collateral blood flow.

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 Approach to Stroke 173

Rx : ----- Active space -----

Initial Rx :
• O2 therapy • Antihypertensive : If BP > 220/110
• GRBS (> 185/110 : In procedures)
• ECG

CT-CT angio protocol :

CT No bleed CT angio

Thrombolyse :
10% : Bolus
Alteplase 0.9 mg/kg
90% : 1 hr infusion
(Or)
Tenecteplase : 0.25 mg/kg (Direct dose)

om
Thrombectomy

l.c
(Based on CT angio) (Within first 24 hours)

ai
gm
@
56
After 24 hours :
t4

• Repeat CT • Single antiplatelet (Aspirin/

hi

• Warfarin (If cardioembolic) ticagrelor > clopidogrel)

c
ra

• Atorvastatin (If LDL > 100)

al
r aw
ag

Carotid endarterectomy/carotid stenting (If needed).

|
w
ro

Criteria for thrombolysis :

ar
M

1. No bleed in CT. 4. Platelets > 1,00,000. 7. No neoplasm.

©

2. Presents ≤ 4.5 hours. 5. GRBS : N . 8. No Sx in past 3 months.

3. > 18 yrs. 6. BP < 185/110.

Brainstem Lesions 00:34:54

Crossed hemiplegia : I/L LMN cranial nerve palsy + C/L hemiplegia.

Midbrain Syndromes :
Supplied by : PCA (P1).

Ventral midbrain syndromes :

Weber Claude Benedict
Site Base of midbrain Tegmentum Weber + Claude + subthalamic nucleus
• I/L LMN CN III palsy
• I/L LMN CN III palsy • C/f of Weber + Claude
C/f • C/L ataxia + tremor (D/t Dentato-rubro-
• C/L hemiplegia • C/L hemiathetosis
thalamo-cortical fibers)

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 174 Medicine

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

Dorsal midbrain syndromes :
M/c/c : Pinealoma.
Parinaud Nothnagel (Anterior)
• Vertical gaze palsy :
Sunsetting sign : Upper gaze palsy
• Overactive LPS Lid retraction (Collier’s sign)
• Vertical gaze palsy
• Argyll Robertson pupil :
• CN III palsy
- Accommodation reflex +
• C/L ataxia
- Pupillary reflex -
• Skew deviation of eye/pseudo-abducens palsy/
convergence retraction nystagmus

Pontine Syndromes :
Supplied by : Basilar arteries.

om
l.c
Dorsal pontine : Ventral pontine

ai
Foville syndrome Millard Gubler syndrome Raymond syndrome

gm
• F : I/L facial nerve palsy @
• F : I/L LMN facial nerve palsy
• S : Sixth nerve palsy
56
• G : I/L gaze palsy (D/t PPRF involvement) • S : Sixth nerve palsy
t4

• H : C/L hemiplegia
• H : C/L hemiplegia • H : C/L hemiplegia
chi
ra
al
aw

Medullary Syndromes :
r
ag
|
w
ro
ar

Medial (4M) : Lateral (4S) :

M

• Motor nucleus of CN III, IV, VI, XII • Spinothalamic tract

©

• Medial longitudinal fasciculus (MLF) • Spinocerebellar fibres

• Motor tract (CST) • Sympathetic
• Medial Lemniscus • Spinal nucleus of CN V

Medial medullary syndrome Lateral medullary syndrome

• Vessel : V4 (Vertebral artery) > PICA
• CN involvement :
- V : Spinal nucleus Numbness (I/L face)
• I/L CN XII palsy - VII : NTS Loss of taste (Anterior 2/3rd of tongue)
• CST (Crossed) : C/L hemiplegia - VIII : Vestibular nucleus Ataxia, tinnitus, vertigo
• MLF : I/L internuclear - IX & X : Nucleus ambiguus Dysphagia, nasal regurgitation
ophthalmoplegia - X : Dorsal nucleus ANS symptoms
• Medial lemniscus (Crossed) : • Sympathetic involvement Horner’s syndrome
C/L proprioception loss • Posterior column : Spared
• Spinothalamic tract (Crossed) : C/L pain and temperature loss
• Motor involvement : -
• Spinocerebellar fibres : Ataxia

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 Neuromuscular Dysfunction and Spinal Cord Diseases 175

NEUROMUSCULAR DYSFUNCTION & ----- Active space -----

SPINAL CORD DISEASES

LMN : Pure Motor Presentation 00:00:06

Anterior horn cells (AHC) : Neuromuscular junction (NMJ) : Muscle :

• Asymmetrical • Repetitive activity ↑weakness • B/L symmetrical
• Distal > proximal • Fluctuating weakness • Proximal > distal
• Wasting > weakness • Diurnal variation • Predominant : LL weakness
• Fasciculations • Ophthalmoplegia + diplopia • Reflexes : Preserved

om
• Masseter muscle involved • Persistent

l.c
MND.

ai
• Acquired

gm
Myasthenia gravis. @
56
Inflammatory muscle diseases :
t4
hi

• Polymyositis.
c
ra

• Dermatomyositis.
al
r aw

Myasthenia Gravis
ag

00:03:02
|
w

• F > M.
ro
ar

• 20 - 40 yrs (> 60 yrs : Second peak in males).

M
©

• Autoimmune disease (T + B mediated).

Antibodies :
1. Anti ACh receptors antibodies (Specific) on postsynaptic membrane :
- 80 - 85% : generalized myasthenia 70% : Thymic hyperplasia.
10% : Thymoma.
- 50% : Ocular myasthenia.
2. Anti-MuSK antibody :
- Seen in 50% pts with ACh R antibody -ve.
- Absent in ocular myasthenia.
- Not a/w thymoma involvement.
- A/w tongue fasciculations.
- Neck extensor weakness.
- Only females.
3. Anti-LRP 4 Ab (If other Ab - ).
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 176 Medicine

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

Ocular symptoms (m/c) :
• Ophthalmoplegia.
• Diplopia (Binocular).
• Ptosis (Asymmetrical with pupil sparing).
• Medial rectus involved.

Progression : Ocular symptoms

15-20% 80%

Disease progression
No progression of disease.
Pharyngeal muscle involvement :

om
• Dysphagia

l.c
ai
• Dysarthria
gm
@
• Repeated chewing Fatigue
56
t4

(Masseter
chi

involved)
ra
al
raw

Proximal muscles involvement (LL)

ag
|
w

Respiratory muscle involvement.

ro
ar

Ix :
M
©

• Single nerve fibre electromyography : Most sensitive test.

• ACh receptor antibody : Most specific test.
• Ice pack test
• Neostigmine test ↑Conduction.
• Edrophonium test

Nerve conduction study :

Differentiate b/w MG vs. LEMS :
MG LEMS
Baseline CMAP N ↓↓↓
Low frequency RNST response Decremental Variable
High frequency RNST response Incremental > 100%
CMAP : compound muscle action potential
RNST : Repetitive nerve stimulation test

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 Neuromuscular Dysfunction and Spinal Cord Diseases 177

Rx : ----- Active space -----

• DOC : Pyridostigmine.
• Pharyngeal involvement + Steroids + Azathioprine.
• Myasthenic crisis IVIG plasma exchange.

S/e :
Cholinergic crisis (D/t excess pyridostigmine) :
• Diarrhea. • Emesis.
• Urination. • Lacrimation.
• Miosis. • Lethargy.
• Bradycardia. • Salivation.

Note :
• Lambert Eaton myasthenic syndrome (LEMS) :

om
- Ab against P/Q Ca2+ channels (Pre-synaptic).

l.c
ai
- Paraneoplastic (D/t small cell carcinoma of lung).
gm
- Predominant : Proximal LL muscle involvement. @
56

- ANS involvement + .
t4
hi

- Rx : 3,4-Diaminopyridine.
c
ra
al

• Chronic progressive external ophthalmoplegia (Mitochondrial disease) :

aw

- Ptosis
r
ag

Without diplopia.
- Ophthalmoplegia
|
w
ro
ar

Motor Neuron Disease (MND) 00:14:30

M
©

α and γ motor neurons degeneration (Ventral horn of SC).

Types :

Pure LMN : Pure UMN : UMN + LMN :

• Spinal muscle atrophy. 1° Lateral sclerosis. Amyotrophic lateral
• Kennedy's disease sclerosis (ALS).
(X-linked).
ALS :
M > F (50 - 60 yrs).
Cause :
• Mostly sporadic.
• 10% : Cu - Zn superoxide dismutase mutation.

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 178 Medicine

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

Structures degenerated & clinical features :
Structure degenerated Clinical features
Distal asymmetrical involvement of UL :
AHC Wasting/atrophy Fasciculations Loss of dexterity/tone
LMN (Forearms + hands)
Bulbar nuclei (40%) Bulbar palsy
• Exaggerated reflexes
CST
UMN • Weakness
Corticobulbar fibres (25%) Pseudobulbar palsy

Bulbar vs. pseudobulbar palsy :

Bulbar palsy Pseudobulbar palsy
Dysarthria Bulbar Pseudobulbar

om
• Wasted
• Small

l.c
Tongue • Atrophic + fasciculations
• Spastic

ai
• Flaccid

gm
Gag reflex - @ ↑↑
56
t4

• Dysphagia • Emotional incontinence

hi

Other features • Nasal twang • Dysphonia Aspirations

c
ra

• Nasal regurgitations • ↑↑Jaw jerk

al
raw

Spinal Cord (SC)

ag

00:21:23
|
w

• Length :
ro

Start : Atlas (Upper border).

ar

- Spinal cord : 45 cm
M

End :
©

• L1 (Lower border) Adults.

• L3 Children.
- Spinal canal : 70 cm.
Conus Medullaris vs. Cauda Equina :
L2
Spinal segments vs. Vertebra :
L3
Lumbar swelling
L4 Segments (31) Vertebra (33)
L5
S1 Involved in C8 C7
Epiconus
S2 cauda equina T12 T12
S3 syndrome
Involved in conus L5 L5
Conus S4 medullaris S5 S5
S5 syndrome C1 C4
C1
Pia mater : Upto
tip of coccyx

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 Neuromuscular Dysfunction and Spinal Cord Diseases 179

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

Conus medullaris Cauda equina (Radiculopathy)
Roots involved S3-C1 L2-C1
Extent/symmetry B/L symmetrical involvement U/L Asymmetrical involvement (Chronic)
Motor symptoms - Variable (Depends on roots involved)
Anal/bulbocavernosus reflexes Loss of reflexes Knee jerk (L3/ L4)
Reflexes
lost Ankle jerk (S1/S2)
Bladder + (Urinary incontinence) -
involvement
Sensory
Saddle anaesthesia Variable patterns
symptoms
Funicular pain
Pain Radicular/Root pain (Shock like)
(Deep seated/dull ache)

om
l.c
ai
Tracts & their Representation :

gm
L M @
Posterior column : S L T C
56
M L
t4
chi
ra
al
aw

Spinothalamic tract
r
ag

C T L S
|

Corticospinal tract M L
w
ro
ar

AHC
M
©

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 180 Medicine

----- Active space ----- Myelopathy 00:28:57

Sensory/motor/ANS symptoms d/t SC pathology.

Types :

Compressive myelopathy. Non-compressive myelopathy.

Compressive Myelopathy :
Extramedullary
Intramedullary
Intradural Extradural (M/c)
Vertebral issues :
• Fracture
• Oligodendroglioma
• Neurofibroma • TB
Etiology • Ependymoma
• Meningioma • Metastasis

om
• Syringomyelia
• Abscess

l.c
• Disc prolapse (M/c)

ai
gm
Presentation Neurogenic claudication (surest sign) : Back pain ↑se on standing erect
Pain Funicular pain
@ Root pain
56
t4

CST involvement Late (Sacral sparing) Early

chi

• Suspended sensory loss

ra

Sensory loss -
al

• Dissociative sensory loss

aw

+ -
r

LMN features
ag
|

Bowel & bladder

w

Siginificant Early incontinence

ro

involvement
ar

+
M

Trophic changes Rare

©

Non-compressive Myelopathy :
Causes :
VITAMIN (Mnemonic) :
• Vascular & demyelinating : NMO and MS.
• Inherited : Friedreich's ataxia.
• Toxins : Arsenic.
• Autoimmune : Sarcoidosis, Behcet's.
• Metabolic : Vit. B12/Cu/Vit. E deficiencies Posterolateral cord involvement.
• Infection : Acute transverse myelitis (Post-infectious).
• Neoplasia.

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 Basics Of Hematology 181

BASICS OF HEMATOLOGY ----- Active space -----

Stem Cells 00:01:00

Stages :
Multipotent hematopoietic stem cell (MHSC)
10 - 14 days :
Progenitor cells
• Time taken for bone marrow
recovery post chemotherapy.
Precursor cells
• ↑R/o infections.
Mature cells.

om
Stem

l.c
Self renewal : Proliferate and differentiate by cell

ai
gm
retaining undifferentiated state Stem
@ cell
56
Mature
t4

Stem cell abnormalities are difficult to cure.

hi

cell
c
ra

Derivatives :
al
r aw
ag

Common myeloid progenitor (CMP) Common lymphoid progenitor (CLP)

|

IL-7
w
ro

• Thrombopoietin • IL-3 • GATA-2

ar

• NOTCH pathway B cells T cells NK cells

(TPO source : Liver) • GATA-1
M
©

Megakaryocyte erythroid Granulocyte monocyte

progenitor (MEP) progenitor (GMP)

RBC Platelets Neutrophil Eosinophil Basophil Macrophage

Receptors :
• CXCR4 : Retains stem cell within marrow
(CXCR4 blocker : Plerixafor To harvest stem cells from blood).
• CXCL12.

Hematopoiesis 00:07:35

Erythropoietin (EPO) : Note :

Rx of anemia in CKD : Roxadustat,
• Source 90% kidney : P eritubular interstitial fibroblasts daprodustat.
(Cortex & outer medulla). • Oral drugs.
10% liver. • HIF prolyl hydroxylase inhibitors (PHI).
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 182 Medicine

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

Stimulus :
Hypoxia (Most important)
+ -
Hypoxia inducible factor (HIF) a No dimer formation

HIF α-HIF β dimer EPO Prolyl hydroxylase Hydroxylated EPO

EPO gene transcription. Binds to VHL (Von Hippel-Lindau)

Undergoes proteasomal degradation.

RBC Development :
IL-3, GM-CSF Blood forming unit erythroid, BFU(e)
MEP

om
(EPO independent)
1st EPO dependent step

l.c
ai
(Iron independent)

gm
Colony forming unit erythroid, CFU(e) @
56

(Maximum EPO receptors + )

t4
hi

1st iron dependent step

c
ra

+ EPO • ↑N : C ratio.
al
aw

• Basophilic cytoplasm.
Proerythroblast (Pronormoblast)
r
ag

• Intact chromatin.
|

• Nucleoli +
w

Erythroblast (Normoblast)
ro
ar
M
©

Early Intermediate Late Reticulocyte : Mature RBC :

(Basophilic) (Polychromatic) (Orthochromic) • Ribosomal rRNA -
Evident RNA (rRNA) +
hemoglobinization • No nucleus

Cytoplasmic maturation Nuclear maturation

• ↓Size
Hemoglobinization of • Condensation of chromatin
Features
cytoplasm (Eosinophilic) • Nucleoli disappear
• ↓Nucleus : Cytoplasmic (N : C) ratio
Lag leading to
Iron deficiency anemia Megaloblastic anemia
ineffective erythropoiesis

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 Basics Of Hematology 183

Reticulocyte staining : ----- Active space -----

• Supravital stains : Stains rRNA.
- New methylene blue.
- Brilliant cresyl blue.
• Regular stains : Appears as polychromatic macrocytic cell.

Evaluation of Anemia 00:18:55

EPO RBC precursors Erythroferrone Inhibits hepcidin

(Master regulator of iron metabolism).

Hemoglobin Reference Ranges :

Male : < 13 g/dL.
Female : < 12 g/dL.

om
Pregnant females : < 11 g/dL.

l.c
ai
CKD : < 11 g/dL.
gm
@
56
Laboratory Parameters :
t4
hi

Retic count : Number of reticulocytes/100 RBCs.

c
ra
al

Absolute reticulocyte count (ARC) : Retic count × RBC count.

r aw
ag

Hb of patient PCV
Corrected reticulocyte count : Retic count × (or) Retic count ×
|

15 (Desired Hb) 45
w
ro
ar

Corrected retic count

M

Reticulocyte production index (RPI) :

©

Maturation time
(Maturation time : Time taken by reticulocyte to lose rRNA in spleen).

Types of Anemia :
Hypoproliferative Hyperproliferative
• Hemolysis (↑RBC destruction)
Causes ↓Production
• Blood loss
Based on ARC < 1.20 lakh/μL > 1.20 lakh/μL
Based on RPI <2 > 2.5

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 184

----- Active space ----- APPROACH TO ANEMIA : PART 1

Key features of stages of RBC maturation :

Normoblast Reticulocyte Mature RBC
Nuclear DNA + - -
RNA in cytoplasm + + -
In marrow + + +
In blood - + +

Normal bone marrow

(Cellularity : 100 - Age)

om
Classification :

l.c
ai
gm
@
Hypoproliferative anaemia
56

(RPI < 2 OR ARC < 1,20,000/µL)

t4
chi
ra
al
aw

MCV < 100 fL : MCV > 100 fL :

r
ag

Normocytosis or microcytosis Macrocytosis.

|
w

(80 - 100 fL) (< 80 fL)

ro
ar
M
©

Iron deficiency Anaemia of chronic disease Sideroblastic anaemia β-thalassemia

anaemia : IDA. (↑Hepcidin). (↓Protoporphyrin). trait/minor.

Absorption in Small Intestine :

Nutrients
Proximal small intestine Duodenum Iron (D2)
(2/5 )
th
Jejunum Majority of nutrients
• Vitamin B12
Distal Small Intestine
Ileum • Mg
(3/5th)
• Bile acids

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 Approach to Anemia : Part 1 185

Iron - Absorption, RDA and Distribution 00:04:48 ----- Active space -----

Absorption of Fe2+ : Hemoglobin synthesis

Uptake by liver :
Luminal Bone marrow Sinusoidal endothelial cells
membrane Duodenal cell Basolateral Produces
membrane
Heme carrier protein Bone morphogenic
Fe2+ protein
(Heme
iron) Fe3+ + transferrin :
Fe3+ Binds to transferrin
Duodenal Transferrin bound iron receptor 2 (TFr2)
Fe3+ cytochrome B Fe3+ (Storage)
Hephaestin Hemojuvelin
(Non- reductase +
(Ceruloplasmin
heme HFE gene
in brain)

om
iron) SMAD pathway

l.c
ai
Fe2+ Fe2+ Fe2+

gm
DMT-1/NRAMP2 Ferroportin Hepcidin production
@ - (Master Regulator)
56
t4
hi
c
ra
al

Dietary iron absorption : 10%.

r aw

Inducers and inhibitors of iron absorption :

ag
|

Inducers Inhibitors
w
ro

• Phytate
ar
M

• Vitamin C • Tannate
©

• Acidic pH • Oxalate
• Ca2+ supplements
RDA of Iron :
RDA (mg)
Male 1
Female 1.2 - 1.5
IInd trimester 3
Pregnancy rd
III trimester 4-5

RDA of iron for erythropoiesis : 25 mg D iet (1 mg).

Recycling from macrophages
(Reticuloendothelial system).

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 186 Medicine

----- Active space ----- Distribution of Iron :

Total iron

66% (2/3rd) : 25 - 27% : Storage 0.08% :

In hemoglobin. Circulation
Ferritin > Hemosiderin (Transferrin).
(water soluble). (water insoluble).

Note :
Hemochromatosis :
Mutation in :
• HFE

om
• Hemojuvelin ↓Hepcidin Iron overload state

l.c
• TFr2

ai
gm
Anaemia of Chronic Disease @ 00:17:45
56
t4
hi

Pathophysiology :
c
ra
al

Inflammation :
aw

• ↑TNF- α
r
ag

-
• ↑ IL-6 ↑Hepcidin Ferroportin Irontrapped inside the cells
|
w

• ↑Activin (↓Iron recycle)

ro
ar
M

Inhibitors of hepcidin :
©

• Erythroferrone.
• Low iron transferrin complexes.
• Hypoxia.
• Matriptase.

Note :
Iron resistant iron deficiency anaemia (IRIDA) :
• Inherited condition (Resistant to oral iron).
• Pathophysiology :
-
Deficiency of matriptase-2/TRPMSS-6 Hepcidin cleavage.
• C/f : Similar to anaemia of chronic disease.

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 Approach to Anemia : Part 1 187

Comparison of Anaemias 00:22:50 ----- Active space -----

Anaemia
Features Chronic β-thalassemia
Iron deficiency Sideroblastic
disease trait
• Iron store measure.
S. ferritin
• +ve acute phase ↓↓ Normal/↑ Normal/↑ Normal
(30 - 300 ng/mL)
reactant.
S. Iron Transferrin bound
↓ ↓↓ ↑ Normal
(50 - 150 μg/dL) iron (Circulation)
TIBC Iron binding capacity ↑
↓ ↓ Normal
(240 - 360 μg/dL) of transferrin (↑Soluble TFr)
TSAT (~ 33%) S. Iron/TIBC x 100 ↓ ↓ ↑ Normal
Dimorphic :
• Inherited :

om
• NCNC NCNC
Morphology of RBC Microcytic -

l.c
• MCHC (TB/RA : MCHC)
• Acquired :

ai
gm
Macrocytic
@
56
TIBC : Total iron binding capacity.
Note :
t4

TSAT : Transferrin saturation.

hi

β-thalassemia trait (β β+/ β β0) :

c

NCNC : Normocytic normochromic.

ra
al

All parameters normal except : MCHC : Microcytic hypochromic.

aw

RA : Rheumatoid arthritis.
• Hb : 10g/dL.
r
ag

TB : Tuberculosis.
• MCV : ↓.
|
w

• Hb A2 : 4 - 8% (Hb electrophoresis).
ro
ar
M
©

IDA 00:32:23

Stages of Iron Deficiency :

Features
Negative iron balance • ↓ S. ferritin
(Latent stage) • Non-symptomatic
• ↓ TSAT
Iron deficient • ↑ TIBC
erythropoiesis • Symptoms +
• Normocytic normochromic cells
Iron deficiency • ↓ Hb
anaemia (IDA) • Microcytic hypochromic cells

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 188 Medicine

----- Active space ----- Causes :

Blood loss (M/c).
↑Iron requirements : Chronic kidney disease.
Malabsorption : Celiac disease.
Nutritional.
Hookworm infection.

Clinical Findings :
• Flattening of nail/koilonychia.
• Mild papillary atrophy of tongue.
• Angular stomatitis.
• Dysphagia

om
Plummer Vinson syndrome.
• Esophageal webs

l.c
ai
gm
Plummer Vinson syndrome
@
56
t4
hi
c
ra
al
raw
ag
|
w
ro
ar
M

koilonychia Angular cheilosis

©

Ix :
Bone marrow study :
• Gold standard.
• Prussian blue stain (Hemosiderin).
Blood parameter :
Iron indices :
• Most specific : ↑Soluble TFr (↑) ratio.
Log ferritin
• Red cell distribution width : ↑ (Anisopoikilocytosis).
• Erythrocyte zinc protoporphyrin : ↑.
• Reticulocyte - Hb content : Low ( < 29).
• Reticulocyte - Hb equivalent : Low (1st peripheral blood marker).

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 Approach to Anemia : Part 1 189

Rx : ----- Active space -----

• Oral liposomal (Sucrosomial) iron : 30 mg.

• Ferric carboxymaltose (FCM) inj.
OR 2.4 x body wt. x (Target Hb - Pt. Hb) + 1000
Iron isomaltose injection
(S/E of FCM : Hypophosphatemia d/t defect in FGF-23).

Post iron therapy :

Timeline to ↑
Bone marrow iron stores 2 days
Reticulocyte - Hb equivalent 4 days
Reticulocyte count 7 days
Hb 2 weeks

om
l.c
Refractory IDA : No ↑in Hb for > 1 month.

ai
gm
Sideroblastic Anaemia @ 00:34:43
56
t4

• ↓Protoporphyrin Ineffective erythropoiesis ↑Iron absorption (↑ S. iron).

chi
ra

• Iron form ring around nucleus : Ringed sideroblast.

al
r aw

Types :
ag
|

• Inherited (M/c) : D/t defective X-linked ALA synthase (M/c).

w
ro

• Acquired causes :
ar
M

a. Myelodysplastic syndrome (MDS) : SF3B1 mutation (Poor prognosis).

©

b. Copper deficiency.
c. Toxicity of :
- Lead.
- Alcohol.
- Zn.
- Chloramphenicol.
- INH.

Normal marrow with Prussian blue stain Ringed sideroblast

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 190 Medicine

----- Active space ----- Macrocytic Anemia 00:44:33

• Hypoproliferative.
• MCV : > 100 fl.

Types :

Megaloblastic : Non-Megaloblastic :
Lag in nuclear maturation. - Megaloblastic changes.

Non-Megaloblastic Macrocytic Anemia 00:45:35

Etiology :

om
1. Reticulocytosis :

l.c
• Macrocytosis.

ai
gm
• Polychromatic : Identified by rRNA (Supravital staining).
@
56

2. Bone marrow failure syndromes :

t4
hi

• Aplastic anemia.
c
ra
al

• Myelodysplastic syndrome :
aw

Mutations of :
r
ag

- SF3B1 (m/c) Sideroblastic anemia.

|
w
ro

- 5q deletion Macrocytic ± megaloblastic anemia.

ar

(Better prognosis)
M
©

3. Alcohol :
• Ringed sideroblasts (M/c).
• Macrocytosis ± megaloblastic changes.

4. Liver disease :
• Macrocytosis.
• Target cells.

5. Hypothyroidism.
6. Hyperlipidemia.
7. COPD. Target cells
8. Scurvy.
9. Myeloma.

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 Approach to Anemia : Part 1 191

Megaloblastic Macrocytic Anemia 00:48:40 ----- Active space -----

Pathogenesis :
- Nuclear maturation

Megaloblasts (In marrow)

Apoptosis
Ineffective erythropoiesis

Hypoproliferative anemia. Hypercellular marrow :

Erythroid hyperplasia
(Compensatory).
Investigations :
Peripheral smear :
• Macrocytosis : M/c finding.

om
l.c
• Pancytopenia : Trilineage involvement (15-20%).

ai
gm
• Normal reticulocytosis.
• Hypersegmented neutrophils : Earliest finding. @
56
t4

• Dyserythropoiesis. Hypersegmented neutrophil

chi
ra
al

Howell Jolly bodies Cabot’s ring Basophilic stippling

r aw
ag
|
w
ro
ar
M
©

Bone marrow aspirate :

• Erythroid hyperplasia.
• Megaloblastic erythropoiesis.

Etiology : Megaloblasts

Vitamin B12 Folate Thiamine Orotic Drugs

deficiency deficiency aciduria ( - DNA synthesis) :
• 6-mercaptopurine
• Hydroxyurea
• Cytarabine

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 192 Medicine

----- Active space ----- Vitamin B12 Deficiency 00:55:30

B12 Metabolism :

RDA : 3 µg/day.

Body stores : 2-5 mg (Enough for 3 yrs) Nutritional deficiency uncommon.

Dietary Intake

Methylcobalamin Adenosylcobalamin
(Major circulating & storage form)

Stomach
R factor (saliva)

om
RF B12 complex

l.c
RF : R factor/haptocorrin

ai
gm
IF : Intrinsic factor
D2 Pancreatic @
TC II : Transcobalamin II
56

enzymes Cubam : Cubilin - amnionless

t4
hi

B12
c
ra

Blood
al

B12
aw
r
ag

D2 - D3 Ileum Marrow
B12 B12 TC II (Major
|

Taken up
w

IF (Parietal cells in body IF Cubam transport

ro
ar

& fundus of stomach) receptors protein)

M
©

Reactions utilizing B12:

• 5-Methyl THFA B12 THFA.
B12
• Methyl malonyl CoA (B12) Succinyl CoA.

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 Approach to Anemia : Part 1 193

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

Pernicious anemia : Ileal disease : Dysmotility : Pancreatic Imerslund Gräsbeck

• > 60 years, F > M • Crohn’s disease • AKA SIBO insufficiency syndrome :
• Antibodies : • TB • Seen in : • Congenital
- Anti-IF Ab • Tropical sprue - DM cubam receptor
(specific) - Scleroderma mutation
- Anti-parietal cell • B12 deficiency +
Ab (Sensitive) : proteinuria
Hypergastrinemia

Gastrin secreting carcinoid > Stomach cancer

om
Presentation :

l.c
• Atrophic glossitis.

ai
gm
• Fatigue. 56
@
• Knuckle hyperpigmentation.
t4
hi

• Neurological :
c
ra

D/t posterolateral cord > Nerve > CNS involvement.

al
r aw
ag

- Posterior column. Order of

|

- Lateral spinothalamic tract.

w

involvement
ro

- Corticospinal tract.
ar
M
©

Management :
Serum B12

<100 pg/mL : 100-200 pg/mL >200 pg/mL

Confirmed B12 deficiency • Serum Homocysteine : ↑ No deficiency
• 5-methyl THFA : ↑(Folate trap)
• Red cell folate : ↓
• Urinary methyl malonyl CoA : ↑

Supplementation :
• Hydroxycobalamin (DOC : ↑ t ½) :
1000 µg I/m or deep s/c.
• Cyanocobalamin.
• Folic acid : 5-15 mg/d × 4 months.

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 194 Medicine

----- Active space ----- Folic Acid (FA) Deficiency 01:02:02

FA Metabolism :
RDA : 100-200 µg/day.

Body stores : 5-10 mg Nutritional deficiency common.

Polyglutamates (From diet)

Monoglutamates
(Absorbed in proximal SI)
Homocysteine Methionine d-UMP
5-methyl THFA THFA
B12
(1 carbon transfer d-TMP

om
& DNA synthesis)

l.c
Etiology :

ai
gm
@
56
Dietary deficiency ↑Requirement : Drugs :
t4

• Haemolysis •
hi

Methotrexate
c
ra

• Myeloproliferative • Pyrimethamine
al
aw

neoplasms. • Triamterene
r
ag

• Phenytoin
|
w

• Sulfamethoxazole
ro
ar

• Sulfasalazine
M

• PPI.
©

Presentation :
Peripheral neuropathy : Pure nerve involvement.

Investigation :
• Serum Homocysteine : ↑
• 5-methyl THFA : ↑(Folate trap).
• Urinary methyl malonyl CoA : Normal.

Treatment :
Folic acid : 5-15 mg/d × 4 months.

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 Approach to Anemia : Part 2 195

APPROACH TO ANEMIA : PART 2 ----- Active space -----

RBC lifespan ↓(< 30 days) Anemia.

Hyperproliferative Anemia :
Causes : Investigations :
• Blood loss • Reticulocyte production index (RPI) : > 2.5.
Reticulocytosis
• Hemolysis • Absolute reticulocyte count (ART) : > 1,20,000/µL.

Hemolysis 00:00:47

Causes :

om
l.c
ai
Inherited : Acquired :

gm
Intra corpuscular defects @ Extracorpuscular
56
(Except familial HUS) defects (Except PNH)
t4
chi
ra

Hemoglobinopathies : Membrane Enzyme deficiencies :

al
aw

• Thalassemia defects • G-6PD

r

• Sickle cell (Cytoskeleton) : • Pyruvate kinase

ag

anemia • Hereditary • 5’ nucleotidase

|
w

spherocytosis
ro

• Elliptocytosis
ar
M

• Ovalocytosis
©

Immune : Non-immune :
• Autoimmune : • Drugs/toxins
- Warm antibody AIHA • Sepsis
- Cold antibody AIHA • PNH
- Paroxysmal cold • Fragmentation
hemoglobinuria hemolysis (HUS, TTP).
• Alloimmune :
- Hemolytic disease of
newborn (HDN)
AIHA : Autoimmune hemolytic anemia - Hemolytic transfusion
PNH : Paroxysmal nocturnal hemoglobinuria reactions (HTFR)
HUS : Hemolytic uremic syndrome • Drug-induced :
TTP : Thrombotic thrombocytopenic purpura - Methyldopa
- Fludarabine.

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 196 Medicine

----- Active space ----- Types of Hemolysis :

Intravascular hemolysis Extravascular hemolysis

Site Within blood vessels (Pathological) Spleen

• LDH ↑↑↑ • Splenomegaly +

• Hemoglobinemia : • LDH↑
- Haptoglobin ↓↓↓ • Haptoglobin↓
- Methemoglobinemia • Ferritin↑ and ↓Fe
Features
• Hemoglobinuria • Indirect hyperbilirubinemia
High coloured urine
• Hemosiderinuria (Jaundice + )
• Indirect hyperbilirubinemia • Urobilinogen↑ and
(Jaundice + ) Stercobilinogen↑

om
l.c
• PNH (m/c) All inherited causes

ai
gm
Causes
• All acquired causes (Except AIHA) 56
@ (Except acute G-6-PD deficiency)
t4

Immune Hemolysis
hi

00:10:20
c
ra
al

Autoimmune Hemolysis :
raw
ag

Paroxysmal cold
|

Warm Ab AIHA Cold Ab AIHA

w
ro

hemoglobinuria (PCH)
ar

Acute rapidly Indolent, slow

M

Presentation Young males

©

progressive anemia progression

Extravascular (Liver) +
Hemolysis Extravascular Extravascular
intravascular
Antigen - I antigen P antigen
IgG (IgG1 > IgG2) & C3 IgM & C3 IgG (Donath
Antibody
(Agglutination - ) (Agglutination + ) Landsteiner Ab)
Temperature of Binds at 4°C
37°C 4°- 30°C
binding Lysis at room temp.

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 Approach to Anemia : Part 2 197

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

Paroxysmal cold
Warm Ab AIHA Cold Ab AIHA hemoglobinuria
(PCH)
• Idiopathic (50%)
• SLE/RA/Systemic sclerosis
• Idiopathic (50%) :
• CLL
Cold agglutinin disease
• Drugs :
(CAD)
- α-methyl DOPA
• Infectious mononucleosis
- Fludarabine
(IMN)
• IBD
• Mycoplasma
• PAN
Causes • Monoclonal IgM (κ/λ) -
• EBV

om
production :

l.c
• Evans syndrome

ai
- Lymphoma

gm
- AIHA with
@ - Myeloma
thrombocytopenia
56
- Waldenstrom
t4

- Component of CVID Children

hi

macroglobulinemia
c

• Autoimmune
ra

• Drug : Lenalidomide
al

lymphoproliferative
r aw

syndrome (ALPS)
ag
|

• Splenomegaly : D/t ↑destruction

w
ro

of IgG & C3 coated RBC

ar
M

(Macrophage mediated) • Splenomegaly

©

• Peripheral blood : • Hepatomegaly

Features -
- Fragmented RBCs & • Acrocyanosis
spherocytes • Raynaud’s phenomenon
- Triangle fragments
- Nucleated RBCs
• Polyvalent antihuman Ig
Direct anti- • Polyvalent antihuman Ig : +ve
: +ve
globulin test • Monovalent Ab :
• Monovalent Ab : -
(DAT)/direct - IgG +ve
- IgG -ve
Coomb’s test - +/- C3
- C3 +ve
Rituximab
Treatment Steroids + Rituximab Supportive
(No role of steroids)

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 198 Medicine

----- Active space ----- Enzymopathies 00:20:20

Autosomal recessive :
• Pyruvate kinase deficiency.
• 5’ nucleotidase deficiency
(Shows basophilic stippling).

G-6-PD Deficiency :
Basophilic stippling
X-linked recessive disorder
1. Acute intravascular hemolysis :
• Drugs (M/c cause) : Primaquine.
- Dapsone. - Rasburicase.
- High dose Acetylsalicylic acid. - Sulfonamides.
- Nitrofurantoin - Methylene blue.

om
• Features :

l.c
ai
gm
- Acute pain abdomen. - High coloured urine.
• Treatment : Stop offending drug. @
56
t4

2. Chronic nonspherocytic extravascular hemolysis :

chi

Peripheral smear :
ra
al

- Bite cells. - Blister cells.

raw

- Hemighosts. - Triangle fragments.

ag
|

- Heinz bodies (Denatured Hb) Detected by supravital stain.

w
ro
ar
M
©

Bite cells Blister cells Triangle fragments

Heinz bodies Helmet cell Howell jolly body

(D/t dyserythropoiesis)

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 Approach to Anemia : Part 2 199

Paroxysmal Nocturnal Hemoglobinuria 00:23:45 ----- Active space -----

M/c acquired cause of intravascular hemolysis.

Pathogenesis :
Acquired somatic mutation : PIGA gene (X chromosome)
Codes for

GPI anchor proteins : Urokinase plasminogen activator receptor (UPAR)

Helps anchor CRP Defect
(Complement regulatory Thrombosis (Budd-Chiari syndrome)
proteins) to RBC surface
Defect
↓CRP : ↓CD55 (Decay accelerating factor)

om
↓CD59 (Membrane inhibitor of reactive lysis)

l.c
↑PNH III RBC

ai
gm
(CRP deficient RBC clones) 56
@
t4

Susceptible to complement
chi
ra

mediated lysis
al
r aw
ag

Recurrent episodes of
|
w

intravascular hemolysis.
ro
ar

Features :
M
©

• ↓ LAP (Leucocyte alkaline phosphatase) score.

• Trilineage involvement.
• Hypercellular (M/c) /normocellular/hypocellular marrow.

Investigations :
Flow cytometry.

Treatment :
Ravulizumab (C5 inhibitor).

Fragmentation Hemolysis 00:28:03

Presentation :
Microangiopathic hemolytic anemia (MAHA) with Thrombocytopenia/thrombotic
microangiopathy (TMA).

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 200 Medicine

----- Active space ----- Pathogenesis :

Endothelial injury (Small vessels)
Subendothelial collagen
exposed
Platelet adhesion

Platelet activation & aggregation

↑Platelet trapping
Thrombus size↑
RBC fragmentation

Thrombocytopenia. Schistocytes/
Crenated RBC.

om
Types :

l.c
ai
gm
Primary : Require immediate Rx 56
@ Secondary :
1. TMA - TTP : 1. Infections :
t4
hi

- CNS > GIT involvement. - EHEC (Shiga like toxin)

c
ra

- MAHA + Thrombocytopenia - Shigella (Shiga toxin)

al
aw

- ADAMTS - 13 : Ab against vWF 2. Autoimmune :

r
ag

metalloproteinase (Acquired) - Scleroderma renal crisis

|
w

- Rx : Emergency plasmapheresis (Anti-RNA polymerase III)

ro
ar

2. Complement mediated HUS : - Catastrophic antiphospholipid Ab

M

- Alternate complement pathway syndrome

©

defect (Complement factor H 3. Malignant hypertension

mutation) 4. Pre-eclampsia (HELLP syndrome)
- Rx : Emergency plasmapheresis 5. Drugs :

Dose dependent : Dose independent : Produce Ab against

• Quinine • Mitomycin ADAMTS 13 :
• Gemcitabine • Calcineurin inhibitors. Ticlopidine.
• Oxaliplatin.

Note :
• March hemolysis : MAHA without thrombocytopenia.
• Prosthetic valve associated hemolysis : Macroangiopathic hemolytic anemia.

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 Approach to Anemia : Part 2 201

Bone Marrow Failure Syndromes 00:37:00 ----- Active space -----

Aplastic Myelodysplastic Pure red cell aplasia (Reticulocytopenia) : 2° myelofibrosis/Myelophthisis :

anemia syndrome (MDS) • RPS-19 mutation. • CKO (↑PTH).
• Associations : • Hairy cell leukemia.
- CLL/Thymoma. • CML.
- HS + Parvo B19 Aplastic crisis . • AML-M7.
infection (Transient)
Aplastic Anemia :
Hypocellularity of marrow (Replaced by fat) Pancytopenia.

Etiology :
• Inherited (5 - 15 yrs) :

Fanconi’s anemia : Dyskeratosis congenita : Shwachman - Diamond syndrome :

om
Gene : FANCA mutation. • Gene : Telomerase Pancreatic malabsorption +

l.c
repair complex defect.

ai
gm
• Triad of :
- Hyperpigmentation. @
56
- Nail dystrophy.
t4
hi

- Leukoplakia.
c
ra

• Acquired :
al
r aw
ag

Non A, non B, Autoimmune : Drugs :

|

Idiopathic PNH
w

(Immune non C hepatitis Eosinophilic fasciitis Dose independent

ro
ar

attack) (Scleroderma like). suppression.

M

• Chloramphenicol.
©

• PTU.
C/f :
Pancytopenia (3 - 6 months) :
• Bleeding (M/c).
• Infections (D/t ↓ ANC).

Rx :
• Equine ATG • Severe case : Allogenic
+ hematopoietic stem cell
Cyclosporine 60 - 70% response. transplant.
+
Eltrombopag

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 202 Medicine

----- Active space ----- MDS :

• Age : > 70 y.
Indian population : Younger females affected.
• M > F.

≥ 10% dysplastic cells Ineffective hematopoiesis Pancytopenia.

(In marrow)
+
1 defining clonal mutation :
• 5q deletion : • SF3B1 mutation : • p53 mutation.
- A/w refractory anemia - Ringed sideroblast + .
(Macrocytic). - Poor prognosis.
- F > M (Indian population).
- Good prognosis : Responds

om
l.c
to lenalidomide.

ai
gm
Risk of AML :
@
MDS 30% AML.
56
t4
hi

Bone marrow :
c
ra
al
aw
r
ag

Hypercellular (80%) Hypocellular (20%) : A/w

|

• 7q deletion and monosomy 7 Poor prognosis.

w
ro

• Pediatric MDS.
ar
M
©

Cellular abnormalities :

RBC : WBC : Platelets :

• Ringed sideroblast. • Döhle bodies. Pawn ball
• Macrocytic. • Toxic granules. megakaryocytes.
• Megaloblast. • Pseudo Pelger - Huët cells.
• Hypersegmented neutrophil.
• 5 - 19% blasts.

Rx :
• Single lineage involvement : • Trilineage involvement :
5q deletion + : Lenalidomide. - Transplant (if fit).
- : EPO (If ↓EPO in blood), - Hypomethylating agents
Luspatercept (New drug). (Azacitidine, decitabine).

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 Myeloproliferative Neoplasms 203

MYELOPROLIFERATIVE NEOPLASMS ----- Active space -----

Myeloid Neoplasms :
Myeloproliferative
Myelodysplastic syndrome (MDS) MPN-MDS overlap
neoplasms (MPN)
≥ 10% dysplastic cells in marrow

Ineffective hematopoiesis
• Chronic myelomonocytic leukemia
Mature terminal myeloid
(CMML)
cell expansion Pancytopenia
• MDS-MPN overlap with SF3B1 mutation

om
+

l.c
Clonal defining mutation

ai
gm
(5q deletion/SF3B1 mutation)
@
56

Features and Types

t4

00:02:25
chi
ra

Features :
al
aw

1. Slow rate of proliferation : Indolent presentation.

r
ag

2. Extramedullary hematopoiesis Splenomegaly.

|
w

3. Dyserythropoiesis/immature cells/arrest of differentiation : - .

ro
ar

4. Can convert to one another.

M
©

5. Risk for AML (1%) : PCRV (Highest risk).

6. Hyperviscosity.
7. Thrombosis (PCRV > ET > PMF).
8. Fatigue : D/t cytokine release.
9. B-symptoms (20%) : Fever, night sweats, weight loss.
Types :
JAK-2 mutation
+ -
• Polycythemia rubra vera (PCRV) : M/c • Chronic myeloid leukemia (CML) : BCR-ABL
• Primary myelofibrosis (PMF) translocation
• Essential thrombocytosis (ET). • Chronic neutrophilic leukemia (CNL)
• Chronic eosinophilic leukemia (CEL)
• Juvenile monocytic leukemia.

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 204 Medicine

----- Active space ----- Approach to Polycythemia 00:08:02

Male : Hb ≥ 16.5 g/dL (PCV : 49%)

Female : Hb ≥ 16 g/dL (PCV : 48%)

Absolute erythrocytosis/ Relative erythrocytosis :

polycythemia (↑RBC mass) (↓Plasma volume)
• Dengue.
• Post viral infection.
2˚ polycythemia 1˚ polycythemia
(↑EPO) (Normal/↓EPO)

Hypoxia : Paraneoplastic EPO PCRV

om
• COPD. production : (Myeloproliferation).

l.c
ai
• Smokers. • RCC.

gm
• High altitude. • Meningioma. @
56
• RAS. • Hepatoma.
t4
hi

• Pheochromocytoma.
c
ra

• Uterine fibroids.
al
raw
ag

Polycythemia Rubra Vera (PCRV) 00:10:09

|
w

Incidence :
ro
ar
M

• 40 - 60 yrs. • F > M.
©

Clinical Features :
↑RBC :
• Hyperviscosity. • Thrombosis : Risk ∝ RBC count.
• Hypertension.
↑WBC :
• ↑Neutrophils ↑Transcobalamin-1 (↑Vit B12 binding capacity).
• ↑Eosinophils.
• ↑Basophils.

↑Platelets :
• Thrombocytosis Microvascular Erythromelalgia : Burning sensation in hands
thrombosis & feet (Proportional to platelet count).
• Bleeding : D/t acquired Von-Willebrand disease.

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 Myeloproliferative Neoplasms 205

Others : ----- Active space -----

• Aquagenic pruritis : • Acne/urticaria.
- D/t WBC proliferation. • ↑Uric acid.
- Specific to PCRV. • Moderate splenomegaly.
Investigations :
• Peripheral smear : Hypoxia induced microerythrocytosis (Small RBCs with
↑proliferation).
• ESR↓↓.
• JAK-2 V617F (M/c)/Exon 12 mutation (Confirmatory).
Treatment :
• Good prognosis.
• Phlebotomy.

om
• H/o thrombosis/ > 60 yrs : Phlebotomy + Aspirin + Ruxolitinib (JAK-2 inhibitor).

l.c
ai
gm
Note :
@
56
Microerythrocytosis also seen in :
t4

• Thalassemia trait. • Hypoxia.

chi
ra
al
aw

Primary Myelofibrosis 00:15:18

r
ag

Incidence :
|
w
ro

• > 60 years. • M = F.
ar
M
©

Associated Mutations :
• JAK-2 mutation (50%). Triple negative :
• Calreticulin gene mutation (30 - 40%). Poor prognosis.
• MPL mutation (Code for thrombopoietin) (10 - 20%).
Pathogenesis :
Hypercellular marrow Megakaryocytes TGF-β Bone marrow Pancytopenia Extramedullary
(Initial phase) dysplasia fibrosis hematopoiesis.

Clinical Features :
• Massive splenomegaly with pancytopenia
(D/d : Hairy cell leukemia, CML in blast crisis). D/t extramedullary
• Portal HTN. erythropoiesis.
• Osteosclerosis.
• Fatigue.
• ↑Risk of thrombosis.
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 206 Medicine

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

Bone marrow aspiration :
• Dry tap.
• Leukoerythroblastic blood picture :
- Tear drop cells. - Cloud like megakaryocytes.

Treatment :
• Poor prognosis.
• Allogenic hematopoietic stem cell transplantation.
• Ruxolitinib (If JAK-2 + )

Note :
• Dwarf-like megakaryocytes CML.
• Giant megakaryocytes Immune thrombocytopenic purpura (ITP).

om
l.c
ai
gm
Essential Thrombocytosis 00:19:19
@
56
Associated Mutations :
t4
hi

• JAK-2 mutation (50%). • MPL mutation (10 - 20%).

c
ra
al

• Calreticulin mutation (30%).

raw
ag

Features :
|
w

• Megakaryocyte hyperplasia (Single lineage involvement) :

ro
ar

Thrombosis Bleeding (D/t few non-

M

>
(Risk ∝ Platelet count)
©

functional megakaryocytes).
• Mild/absent splenomegaly (Low/nil extramedullary hematopoiesis).
• Risk of AML : Minimal.
Investigations :
• Platelets > 4,50,000 cells/μL • Staghorn megakaryocytes.
(Incidental finding). • RBC, WBC : N .

Treatment :
• Aspirin.
• > 60 years/H/o thrombosis/platelets > 9,50,000 cells/μL Hydroxyurea >
Interferon.

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 Myeloproliferative Neoplasms 207

Chronic Myeloid Leukemia (CML) 00:22:53 ----- Active space -----

• JAK-2 - . • Age group : Middle age.

• BCR-ABL + . • M > F.

Pathology :
BCR-ABL translocation : Seen in all cases.
ABL gene (Chr. 9q) : Balanced reciprocal (P210) BCL gene
Myristoyl binding residue Autoinhibits ABL kinase translocation (Chr 22q)

Philadelphia (Ph) chromosome (Seen in 95% cases) :

Foreshortening of long arm of Chr. 22
Constitutive activation of ABL kinase

Acts as docking site for ATP binding

om
l.c
Tyrosine phosphorylation

ai
gm
Dysregulated @
Uncontrolled proliferation of mature & maturing Fairly normal
56

production. granulocytes, RBCs & platelets differentiation.

t4
chi
ra

Extramedullary hematopoiesis ↑↑WBC

al
r aw

Splenomegaly. Leukocytosis.
ag
|
w
ro
ar

Investigations : Features :
M
©

1. Peripheral blood smear : Chronic phase :

• ↑WBC (I lakh/μL). • Asymptomatic ± Hyperviscosity
leukoytosis syndrome.
• Massive Early satiety,
splenomegaly abd discomfort.
• ↑Basophils (Mast cells, histamine). • Acne/urticaria.
• Eosinophilia. • Allergic symptoms.
• ↑Platelet count. • Thrombosis (Minimal).
• ↓RBC (D/t cytokines). • Anemia.
• ↑Uric acid (D/t proliferation). • Hyperuricemia symptoms.
• Blast forms :
- All stages seen. Blast crisis : Blasts ≥ 20%.
- Myelocytes :
Maximum Myelocyte bulge.

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 208 Medicine

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

2. FISH : To detect BCR-ABL translocation.
3. Bone marrow study :
Indications :
• Cytogenetics To rule out additional abnormalities (Double Ph.).
• Quantify blasts.
• To determine degree of fibrosis.

4. LAP(Leukocyte alkaline phosphatase) score : Low (D/t cytochemical abnormal

WBC).

Note :
Low LAP score Seen in PNH, CML.

Management :

om
Treatment :

l.c
ai
Tyrosine kinase inhibitors (TK1) : DOC Side effects
gm
@ • Hypopigmentation
56
t4

• Edema
hi

Imatinib
c

• Tyrosine kinase domain

ra
al

mutations
raw

• Peripheral vascular disease

ag

Nilotinib
|

• Pancreatitis
w
ro

Bosutinib Colitis
ar
M

Dasatinib (Preferred)
©

-
Ponatinib (For T315I mutation)

Outcome :
1. Morphological remission.
2. Cytogenic response : At 6 months.
Bone marrow aspiration : No Ph. chromosome on conventional karyotyping.
3. Molecular response : Monitor by PCR (Quantify BCR-ABL).
I year : < 0.1 %.

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 Acute Myeloid Leukemia 209

ACUTE MYELOID LEUKEMIA ----- Active space -----

Basics of AML 00:00:45

Demography :
• 80% of acute leukemia in adults.
• 10% in children.

Risk factors :
• MDS (SF3B1 mutations). • Radiation.
• MPN. • Alkylating agents : 3 - 10 years.
• PNH. • Topoisomerase-II inhibitors

om
• Benzene. (Etoposide) : 1 - 3 years.

l.c
ai
• Smoking.
gm
@
56
Causes :
t4
hi

Genetic mutation :
c
ra

i. Acquired somatic (Driving mutation) : > ii. Germline :

al
aw

• NPM1 : Good prognosis. • Down’s syndrome. (A/w

r
ag

• FLT3-ITD : Intermediate prognosis. megakaryocytic leukemia)

|
w

(Rx : Midostaurin) • Fanconi’s anemia.

ro
ar

• CEBPA.
M
©

Pathophysiology :
Genetic mutation 1. Arrest of differentiation ↑↑↑Myeloblasts (M/c)
2. Uncontrolled proliferation
Presentation : Inhibits hematopoiesis.
• Pancytopenia :
- Bleeding (M/c).
- Fatigue.
- Skin & soft tissue infections.
• Hyperviscosity symptoms : D/t blast cells in blood (CNS and testes not invaded).
• Hepatosplenomegaly.
• Gingival involvement. (M4, M5 : Monoblast)
• CNS involvement.
• Chloroma/Myeloid sarcoma (Orbit) : A/w t (8 ; 21).

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 210 Medicine

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

Chloroma : Blast cell accumulation in orbit Leukemia cutis

Classification and Diagnosis 00:12:17

Classification Based on Prognosis (2022) :

om
Favorable : Intermediate : Adverse/Less favorable :

l.c
i. t (8 ; 21) or RUNX1 - RUNX1. NPM1 with FLT3-ITD.

ai
Other mutations.

gm
ii. t (16 ; 16) or inv 16 (Involves 56
@
CBF-β/MYH11).
t4
hi

iii. NPM-1 without FLT3-ITD.

c
ra

iv. Biallelic inframe CEBPA.

al
raw

AML Eo t (16 ; 16) :

ag

• A/w eosinophilia.
|
w
ro

• A/w monoblast/myeloblast type.

ar
M

WHO update : Genetic mutations + A ML (Presence of ≥ 20% blasts : Not

©

necessary for diagnosis).

Diagnostic Steps :

Morphology : Cytology : Immunophenotyping : Cytogenetics : Molecular

Myeloblast • MPO. CD markers. Translocations. genetics :
features. • Sudan black. Mutations.
Markers :
Phenotype Marker
Myelomonocyte CD 14
Monocyte CD 11c, CD 13, CD 14
Megakaryocyte CD 41, CD 61
Erythroid Glycophorin, spectrin
Myeloblast CD 11B, CD 13, CD 33, CD 117
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 Acute Myeloid Leukemia 211

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

Myeloblast Bone marrow : AML

Management 00:22:07

7 + 3 regimen :
• 7 days : Cytarabine x 2 cycles
• 3 days : Daunorubicin

om
l.c
ai
gm
Bone marrow evaluation :
@
Molecular remission : Minimal residual disease (MRD)
56
t4

(Target : < 0.01% blasts)

chi
ra
al
aw

Achieved MRD Not achieved MRD/High risk

r
ag

patients
|
w

High dose cytarabine.

ro
ar

Allogeneic hematopoietic stem

M

cell transplant.
©

Other drugs :
• FLT3-ITD - : Midostaurin.
• Anti-CD 33 : Gemtuzumab, ozogamicin.
• BCL-2 - : Venetoclax.
• Hypomethylating agents :
- Azacitidine.
- Decitabine.

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 212 Medicine

----- Active space ----- Acute Promyelocytic Leukemia (APML) 00:24:07

• Arrest of differentiation : At promyelocyte (Earlier : AML M3).

• M/c : In young age.
• Mortality : Early d/t DIC.

Types :
Hypergranular (2/3rd) Hypogranular (1/3rd)
TLC ↓ ↑
Favorable + -
Faggot cells
(Packed Auer + -
rods + )

om
l.c
Dumbbell Butterfly

ai
gm
@
56

Nuclei shape
t4

Faggot cells
chi
ra
al
raw
ag
|
w

Rx :
ro
ar

Sanz criteria :
M
©

High risk : Low risk :

• TLC : < 10,000
Rx : ATRA • Platelets : > 40,000
+
Arsenic trioxide Rx : ATRA
+ +
Idarubicin. Arsenic trioxide.
ATRA (All trans retinoic acid) :
• Differentiating agent.
• S/e :
- Differentiation syndrome (Rx : Steroids).
- ↑ICT.

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 Lymphoid Series Neoplasms 213

LYMPHOID SERIES NEOPLASMS ----- Active space -----

B-Cell Maturation & Neoplasms 00:00:44

In Bone Marrow :

Precursor B-cell ALL : Common lymphoid CD34, HLA DR

• Children (80%), Adults (20%) progenitor (CLP)
• Pro B-ALL
Pro B-cell CD19, CD34, HLA DR
• Pre B-ALL (M/C) :Best
prognosis Pre B-cell B-cell markers : CD19, CD20, CD21,

om
• Immature B-ALL CD22, CD79a, CD79b

l.c
Specific markers : CD10 (CALLA), tdt

ai
gm
Immature B-cell @ B-cell markers, SIgM (Surface IgM)
56
t4
hi

In Blood & Lymph Nodes : Naive B-cell

c

B-cell markers, SIgM ± CD5

ra
al
aw

Majority Few
r
ag

Apoptosis Lymph node

|
w

Fails Interfollicular area

ro
ar

Monoclonal (k/λ) Acquires SIgD

M
©

proliferation
Majority Few
Germinal center Mantle cell layer
Monoclonal lymphocytosis
(CD10, CD23 (Activation (Pre-germinal layer)
(≥ 5000 cells/μL)
markers), Dysregulated + CD5
BCL-6) + Cyclin D1
Chronic lymphocytic
leukemia (CLL) Mantle cell lymphoma
Diffuse large B-cell
B-cell markers, B-cell markers, SIgM,
lymphoma (DLBCL) :
SIgM, CD5, CD23 SIgD, CD5, Cyclin D1
M/C NHL
• Burkitt’s lymphoma
• Follicular lymphoma
B-cell markers, SIgM,
SIgD, CD10, CD23, : Disorders
dysregulated BCL-6 : Markers
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 214 Medicine

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

In germinal/activation/maturation center:

ABC DLBCL Activated B-cell (ABC) Marginal zone Marginal zone B-cell
plasma blast cell lymphoma (MZL) : (Post-germinal center) markers,
Extranodal SIgM, SIgD
C19, CD38, CD138 Plasma cell Memory B-cells
(Polyclonal)
Loses CD19 • Hodgkin’s disease
CD138, CD38 • Small lymphocytic lymphoma
Monoclonal
(Counterpart of CLL).
Plasma cell dyscrasia : • Hairy cell leukemia.
• Multiple myeloma • Waldenstrom’s macroglobulinemia.
• Waldenstrom’s

om
macroglobulinemia

l.c
• AL Amyloidosis

ai
gm
• Heavy chain disease 56
@
t4

Immunophenotyping :
chi
ra

CD5 CD10 CD23

al
aw

CLL + - +
r
ag

+ - -
|

Mantle cell lymphoma

w
ro

Follicular lymphoma/DLBCL/Burkitt’s lymphoma - + +

ar
M

Marginal zone lymphoma/memory B-cell lymphomas - - -

©

T-cell Neoplasms 00:21:57

Precursor T-cell Leukemia/Lymphoma :

• Adolescents (M/c).
• Part of development occurs in thymus

Mediastinal widening

Respiratory symptoms.

Mediastinal widening

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 Lymphoid Series Neoplasms 215

Mature T-cell Neoplasms : ----- Active space -----

Mycosis fungoides Enteropathy EBV associated Anaplastic large cell Angioimmunoblastic

(Cutaneous T-cell associated NK-T cell lymphoma : lymphoma :
lymphoma / T-cell lymphoma : • A/w post-breast Midline nasal deformity
Sezary syndrome) lymphoma Presents with implant + (D/d : Wegener’s
nasal mass • ALK + , CD30 + granulomatosis)
Note :
Celiac disease (Premalignant condition):
↑ R/o :
• SCC esophagus.
• Adenocarcinoma of intestine.

om
Erythematous atrophic patches : • Enteropathy associated T-cell lymphoma.

l.c
Mycosis fungoides

ai
gm
Virus Associations of Lymphomas @ 00:24:43
56
t4

EBV : H. pylori associated :

chi

1. Hodgkin’s disease.
ra

Gastric MALToma (Extranodal MZL) :

al

2. Post transplant lymphomas. Histology

aw

A/w non-atrophic pangastritis.

r

3. Primary CNS lymphomas. similar to

ag

HHV-8 :
|

4. NK-T lymphoma. DLBCL

w

• Primary effusion lymphoma.

ro

5. Burkitt’s lymphoma.
ar

• Castleman disease.
M
©

HCV :
HIV :
1. Waldenstrom’s macroglobulinemia.
1. DLBCL
2. Splenic MZL.
2. Burkitt’s lymphoma
HTLV-1 : 3. Hodgkin’s lymphoma
Adult T-cell leukemia/lymphoma. (Lymphocyte depleted &
mixed cellularity)

Flower cell :
• Adult T-cell leukemia/lymphoma.
• Anaplastic large cell lymphoma.
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 216 Medicine

----- Active space ----- Acute Lymphoblastic Leukemia (ALL) 00:29:10

Adult leukemias AML (80%)

ALL (20%) B-cell ALL (80%) Early pre B-cell (M/c)
T-cell ALL (20%)
Childhood leukemias ALL (90%).

Features :
• Pancytopenia.
• Risk of tumour lysis syndrome.
• Bone pain (m/c in children)/difficulty in
walking/limping.
• CNS & testes involvement (Responsible
for refractory disease/relapse).

om
• High counts (Also poor prognosis). Lymphoblasts (ALL)

l.c
ai
gm
ALL vs AML : 56
@
t4

ALL AML
hi
c

Cells Lymphoblasts (Small) Myeloblasts (Large)

ra
al

N : C ratio High
aw

Morphology
r
ag

Nucleoli - +
|

- +
w

Auer rods
ro
ar

• MPO +ve
M

• PAS +ve • Sudan black +ve

©

Cytology
• Acid phosphatase +ve • Non-specific esterase +ve
(Monoblastic lesion)
• Pro B-cell (CD19, CD34, HLADR)
Immunophenotyping • Pre B-cell (B-cell markers, CD10, tdt) CD13, CD33, CD117
• Immature B-cell (B-cell markers, sIgM)
• t(12 ; 21) Good prognosis
• t(16 ; 16)
• t(9 ; 22)
Cytogenetics Bad prognosis • t(8 ; 21) Good prognosis
• t(4 ; 11)
• t(15 ; 17)
• t(1 ; 19)
• Hyperdiploidy Good prognosis
Molecular genetics -
• NOTCH-1 overexpression

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 Lymphoid Series Neoplasms 217

Prognosis : ----- Active space -----

Good Prognosis : Bad prognosis :

• 2-9 years; Female. • Hypodiploidy.
• White. • T-cell ALL.
• Low counts.
• L1 morphology.
• Testes / CNS involvement - .
• B-cell (Early pre-B ALL).
• Hyperdiploidy.
• NOTCH-1.

Treatment :
1. Induction phase : To achieve minimal residual disease (MRD) of 0.01%

om
• Steroids.

l.c
• L-asparaginase : Less preferred in adults d/t side effects

ai
gm
(Pancreatitis & thrombosis). 56
@
• Vincristine.
t4
hi

• Daunorubicin.
c
ra
al

2. Consolidation phase.
r aw
ag

3. Maintenance phase : 6-mercaptopurine (6-MP) & methotrexate.

|
w
ro

Chronic Lymphocytic Leukemia (CLL)

ar

00:37:50
M
©

Features :
• Elderly.
• M > F (Exception : MZL F > M d/t autoimmune association).
• Asymptomatic.

Findings :
• Incidental finding on routine checkup :
- RBC & platelets : Normal.
- Total WBC count : 70,000 - 1,00,000
cells/μL. Small, blue round
- Histopathology : lymphocytes
• Small, blue round lymphocytes.
• Smudge cells. Smudge cells
Histopathology

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 218 Medicine

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

Rai & Binet staging :
• Stage 0 : Only lymphocytosis.
• Stage 1 : Lymphocytosis with lymphadenopathy.

Treatment :
Indications for treatment :
• Bone marrow involvement (Stage 4).
• Richter’s transformation : Low-grade tumour (CLL) High grade tumour
(DLBCL).
• Warm Ab Autoimmune hemolytic anemia unresponsive to steroids.
• Lymphadenopathy + .
• Development of B-symptoms : Fever, weight loss, night sweats.

Drugs used :

om
BR regime : Bendamustine + Rituximab Preferred regime.

l.c
ai
If relapse occurs/intolerance to above regime :
gm
• Venetoclax : BCL-2 inhibitor. @
56

• Ibrutinib : Tyrosine kinase inhibitor.

t4
hi

• Idelalisib : PI3K inhibitor.

c
ra
al
aw

Prognosis :
r
ag

Good prognosis : 13q deletion.

|
w
ro

Bad prognosis : Markers Zap 70, β2-microglobulin.

ar
M
©

Lymphomas 00:44:23

Hodgkin’s Disease V/S Non-Hodgkin’s Lymphoma :

Hodgkin’s disease Non-Hodgkin’s lymphoma (NHL)
• Bimodal peak
• Elderly (Median : 60 years)
Incidence • 15 - 34 years (majority)
• M>F
• M>F
Presentation Asymptomatic painless lymphadenopathy
• Contiguous
Lymph node involvement • Posterior cervical (M/c) > Non-contiguous
Supraclavicular > Axillary
+ : GIT (M/c)
Extranodal involvement - • Lymphomatoid polyposis
• Waldeyer’s ring involvement
B-symptoms More common Less common
Bone marrow involvement - +
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 Lymphoid Series Neoplasms 219

Hodgkin’s disease Non-Hodgkin’s lymphoma (NHL) ----- Active space -----

EBV association + ±( + Burkitt’s lymphoma)

ABVD regimen : R-CHOP regime :
A : Adriamycin R : Rituximab
B : Bleomycin C : Cyclophosphamide
Treatment
V : Vinblastine H : Hydroxy daunorubicin
D : Dacarbazine O : Oncovin (Vincristine)
Brentuximab (CD30 inhibitor) P : Prednisolone
Markers CD15, CD30 -
Non Hodgkin Lymphoma (NHL) 00:49:00

Types of NHL :
High grade Low grade (Good prognosis)

om
• SLL
• DLBCL (M/c)

l.c
• Follicular lymphoma

ai
• Burkitt lymphoma

gm
• Hairy cell leukemia
• Mantle cell
• MZL @
lymphoma (MCL)
56
• Waldenstrom’s macroglobulinemia
t4
chi
ra

MCL v/s Follicular Lymphoma v/s MZL :

al
r aw
ag

Mantle cell lymphoma Follicular lymphoma Marginal zone lymphoma

|

Grade High Low Low

w
ro

• F > M (Autoimmune association)

ar

• Bone marrow
M

• Extranodal involvement :
involvement +
©

- Stomach (M/C)
Features • Extranodal + ↑ risk of relapse
(A/w H. pylori MALToma)
• Non-responsive to
- Salivary gland (A/w Sjogren’s)
R-CHOP regimen
- Spleen (A/w HCV)
• CD10 + , CD23 + • CD5 -
Immunophenotyping CD5 + , Cyclin D1 + • Aberrant BCL-2 > • CD10 -
Dysregulated BCL-6 • CD23 -
• t (11 ; 14)
Cytogenetics t (14 ; 18) t (11 ; 18)
• ↑ Sox-11 (Good prognosis)
Treatment - Rituximab / R-CHOP regime H. pylori management

DLBCL :
• Rapidly progressive. CNS lymphomas
• Extranodal involvement + : Body cavity lymphomas
Effusion lymphomas
Post-transplant lymphomas

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 220 Medicine

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

Types : +
MUM 1 Activated B cells : Poor prognosis.
Germinal cell (M/c) : Good prognosis.
-
Specific : CD10, CD23, Dysregulated BCL-6 > Aberrant BCL-2

Double-hit lymphoma : BCL-2 or BCL-6. + c-myc rearrangement

Triple-hit lymphoma : BCL-2 and BCL-6. (Poor prognosis)

Treatment : R-CHOP regime.

Burkitt Lymphoma :
Chemosensitive (Good prognosis).

om
Types :

l.c
ai
gm
EBV
Types Features
association @
56
Childhood Burkitt/endemic 100% Jaw mass
t4
hi

Abdominal
c

Adult Burkitt/sporadic 70%

ra

mass
al
aw

Starry sky appearance

r

Findings :
ag
|

• t(2 ; 8), t(8 ; 14), t(8 ; 22) C-myc (Chromosome 8).

w
ro

• Marker : ki-67 (↑↑).

ar
M

• HPE : Starry sky appearance.

©

Memory B - Cell Disorders 00:58:37

Hairy Cell Leukemia :

Low grade lymphoma.

Pathogenesis :
Memory B-cells BRAF mutation Hairy cells Spleen Massive splenomegaly
Bone marrow Pancytopenia &
Fibrosis.
HPE : Fried-egg appearance.

Immunophenotyping :CD11c, CD25, CD103, CD123, TRAP + ,

Annexin A1 + .

Hairy cell
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 Lymphoid Series Neoplasms 221

Complications : ----- Active space -----

• Aspergillus infection D/t neutropenia
• Atypical mycobacterial infection

Treatment : Cladribine or Pentostatin.

Note :
Myelofibrosis : Pancytopenia + Massive splenomegaly. Fried egg appearance
Hodgkin’s Disease :
Pathogenesis :
Memory B-cells PDL-1 mutation Reed Sternberg (RS) cells in appropriate
inflammatory background.

Types :

om
l.c
EBV association RS cells Features

ai
gm
Lymphocyte • Worst prognosis
100% @
Absent
depleted • A/w HIV
56
t4

Mixed • M/c in India

hi

70% Classical
c

cellularity • Seen in children & elderly

ra

Classical
al

(CD15 + , CD30 + ) • M/c type in females

aw

Nodular
40% Lacunar • Mediastinal widening +
r

sclerosis
ag

(SVC obstruction)
|
w

Lymphocyte
ro

20% - -
rich
ar
M
©

Non-classical
Lymphocyte • Axillary lymphadenopathy
(CD15 - , CD30 - - Popcorn
predominant • Radiosensitive
CD20 + , CD45 + )

Paraneoplastic association :
• Cerebellar association.
• Minimal change disease.

Reed-Sternberg cell Nodular lymphocyte predominant

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 222 Medicine

----- Active space ----- PLASMA CELL DISORDERS

AKA Plasma cell dyscrasias/paraproteinemia/dysproteinemia.

Types :

Multiple Waldenstrom Heavy AL

myeloma macroglobulinemia chain amyloidosis
disease

Multiple Myeloma 00:01:25

om
Trigger : ↑IL-6 and NF-κB pathway + .

l.c
Age : > 40 yrs.

ai
gm
Pathogenesis : @
56
t4

Memory Activated B-cells Plasma cell : CD19, CD38,

hi

Monoclonal : CD38, CD138

c

B-cells (ABC/plasmablast) CD138 (Polyclonal)

ra
al
aw

Produce clones
r
ag

• IgGκ (M/c). • IgAκ.

> • IgAλ.
|

• IgGλ.
w
ro
ar
M

Presentation :
©

• Bone pain (M/c). With ↑Ca2+ and normal ALP

• Unexplained fracture. (D/t osteolysis).
• Anemia + ↑ESR.
• Hypoalbuminemia + ↑total proteins.
• Hypogammaglobulinemia (Recurrent UTI/pneumonia).
• Radiculopathy/myelopathy.
• Renal manifestations :
- Overflow proteinuria.
- Proximal RTA.
- Light chain cast nephropathy (M/c) : λ chain.
- Light chain deposition disease : κ chain.

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 Plasma Cell Disorders 223

Risk Classification : ----- Active space -----

• t(4 ; 14) Any 1 + : High risk MM.

• t(14 ; 16) 2 + : Double hit MM.
• t(14 ; 20)
• Deletion 17p 3 + : Triple hit MM.
• p53
- : Standard risk MM.

Ix :
Myeloma panel :
1. Serum protein electrophoresis (SPEP).
2. Serum immunoelectrophoresis (SIFE).
3. Serum free light chain ratio (SFLC).

om
l.c
Prognostic marker :

ai
gm
β2-microglobulin.
@
56
Abnormal [Link] electrophoresis
t4
chi
ra

Diagnosis :
al
r aw

Multiple myeloma Smouldering myeloma MGUS

ag
|

Monoclonality : Serum M protein

w

≥ 3 g/dL ≥ 3 g/dL < 3 g/dL

ro

(Protein and immunoelectrophoresis)

ar
M

Bone marrow plasma cells ≥ 10% ≥ 10% < 10%

©

Myeloma defining event (MDE) ≥1 - -

MGUS : Monoclonal gammopathy of undetermined significance.

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

Other variants :
• Solitary plasmacytoma.
• Plasma cell leukemia : ≥ 20% plasma cells in blood.

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 224 Medicine

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

Low/moderate risk :
Bortezomib + Dexamethasone + Lenalidomide
Followed by
Autologous stem cell transplant
(Non-curative).
High risk MM : Replace bortezomib with carfilzomib.
Other drug : Daratumumab (CD38 monoclonal antibody).

Waldenstrom Macroglobulinemia and POEM Syndrome 00:17:27

Waldenstrom Macroglobulinemia :
AKA lymphoplasmacytic lymphoma.

om
Pathogenesis :

l.c
ai
Myd88 mutation Lymphoplasmacytic cells CD19, CD20,
gm
Memory B-cells
@ CD38, CD138, surface IgM
56
t4
chi

Secretes surface IgM.

ra
al

Clinical features :
aw

• ↑IgM :
r
ag
|
w

Cold agglutinin disease : Hyperviscosity Type 1

ro
ar

• Raynaud’s phenomenon. symptoms. cryoglobulinemia.

M
©

• Acrocyanosis.
• No bone lesion or renal involvement.

Rx :
Plasma exchange : PLEX.

POEM Syndrome :
• Associated with Castleman’s disease. • ↑VEGF.
Criteria :
P : CIDP (Chronic inflammatory demyelinating polyneuropathy).
O : Organomegaly.
E : Endocrinopathy (Hypogonadism).
Edema.
M : Multiple myeloma/monoclonality.
S : Skin changes.
Sclerotic lesions.
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 Ckd 225

CKD ----- Active space -----

Anatomy of Kidneys 00:00:55

Structure :

85% : Tubules + Interstitium 10% : Glomerulus 5% : Vessels

WT1 Mutation :
WAGR Syndrome :
• Wilms tumor • Genitourinary abnormalities

om
l.c
• Aniridia • Mental retardation

ai
gm
Denys drash syndrome : @
56
Wilms tumour
t4
chi
ra
al
aw

Triad
r
ag

Early onset renal failure (By 3-5 yrs) :

|

Differences in sexual development :

w
ro

Male pseudohermaphroditism. Diffuse mesangial sclerosis

ar
M

Etiopathogenesis of CKD 00:08:30

©

↓in Functional nephrons.

Etiology :
Diabetic kidney disease (M/c) : Rapid ↓in GFR.
Chronic GN : Associated with IgA nephropathy.
Vascular CKD : Renal artery stenosis Ischemic nephropathy.
Chronic tubulo-interstitial diseases : Inherited : Autosomal dominant polycystic
kidney disease (ADPKD).
Acquired.
Nephron underdosing theory : CKD
↑risk of
Low birth weight ↓Nephrons at birth
Metabolic syndromes

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 226 Medicine

----- Active space ----- Pathophysiology :

↓Nephrons

Glomerular Hyperfiltration : ↑Single nephron GFR (snGFR)

Intraglomerular hypertension

Widens capillary pore diameter

Proteinuria Tubulotoxic

Stimulates interstitial inflammation

TGF β
Fibrosis
Interstitial fibrosis

om
CKD : % of IFTAGS Tubular atrophy

l.c
ai
Glomerular sclerosis

gm
@
56
t4

Staging and Diagnosis

hi

00:18:55
c
ra
al

Glomerular filtration rate (GFR) : OP : Oncotic pressure

aw

HP : Hydrostatic
r

• snGFR x No. of functional nephrons.

ag

• GFR = Net UF pressure x UF coefficient = 125 mL/min pressure

|
w
ro

UF : Ultrafiltration
ar
M

(Capillary HP - Interstitial HP) - (Capillary OP - Interstitial OP)

©

Staging :
Based on GFR :
Stages
G1 G2 G3 G4 G5
GFR (mL/min) 90-125 60-89 30-59 15-29 < 15

N GFR + Evidence of Uremic phase/End stage

kidney disease renal disease (ESRD)
Based on Albumin-creatinine ratio (ACR) :

Stage ACR (mg/g) Significance

A1 < 30 N
A2 30-300 Microalbuminuria : Endothelial damage
A3 > 300 Significant proteinuria/albuminuria
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 Ckd 227

Assessment of eGFR : ----- Active space -----

Creatinine :
• Clearance used to estimate GFR.
• Significant in CKD only if proteinuria + .
• ∝ Muscle mass : ↑In males & African-Americans.
• Undergoes tubular secretion (Overestimates GFR) :
- Trimethoprim
Compete with creatinine for excretion
- Cimetidine

Formulae for adults :

Uses S. Creatinine (S. Cr)
• Cockcroft & Gault
• MDRD
Preferred :

om
• CKD-EPI (Gold Standard)
- Measures GFR directly.

l.c
ai
- Body weight not considered.
gm
- Race considered. @
56

- Standardized assays used.

t4
hi

Formula in children :
c
ra
al

Schwartz equation :
aw

Age K value
eGFR = KS. xCrl
r
ag

1 - 12 yrs 0.53 - 0.55

|
w

Term 0.45
ro

• l : Length of child < 1 yr

ar

• K : Constant Preterm 0.35

M
©

Investigations :
URE : Proteinuria.
** ***
RFT. *
****
USG abdomen :
Kidney size N : > 10 cm
N Kidney on USG with CMD
Small : < 8 cm 8 - 10 cm No. of * ∝ echogenicity :
N /Large :
Sinus > Cortex > Pyramid > Papillae
• DM
• HIV
• Amyloid
• ADPKD
Loss of corticomedullary
differentiation (CMD)
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 228 Medicine

----- Active space ----- TUBULAR DISORDERS

Proximal straight tubule (PST)/Pars recta : Most vulnerable to ischemic injury

• Max. O2 requirement
• Poor blood supply from vasa recta

Type 2 RTA 00:03:50

Aka proximal renal tubular acidosis/

Fanconi’s syndrome.
Proximal Tubule :
• Iso-osmotic resorption

om
l.c
(290 mOsm/L) : Prevents

ai
gm
hyponatremia.
• Maximum resorption of all ions @
56
t4

except Mg2+.
chi
ra
al
raw
ag
|
w

Diffusion Secondary active transporters :

ro

Primary active transporters

ar

Symporters
M

Antiporters
©

Etiology :

Inherited : Acquired :
• Cystinosis (M/c) • Drugs :
AR.
• Wilson’s disease - Tenofovir.
- Outdated tetracyclines.
- Ifosfamide.
- Valproate.
• Plasma cell disorders :
Multiple myeloma/Light chain myeloma.

Clinical Manifestations :
• RFT : N .
• No risk of CKD.

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 Tubular Disorders 229

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

Abnormality Manifestations Clinical presentation

Na+-glucose symport Euglycemic glycosuria U. glucose +ve with N blood glucose
Na+-phosphate symport Phosphaturia Renal rickets (More severe than in type 1)
Na -amino acid symport
+
Amino aciduria Frothy urine & Muscle wasting
Loss of H2O & Na+ Salt wasting/dehydration Hypokalemia : RAAS activation
• Mild acidosis (HCO3- : 16 - 18 mEq/L) :
NAGMA/hyperchloremic
Na -H antiport
+ +
↓Excretion of acid compensated by intact cortical CD.
metabolic acidosis
• Urine anion gap : +ve.

Type 1 RTA 00:15:45

Aka distal RTA.

om
I Cells Of Collecting Duct :

l.c
ai
gm
@
56
t4
chi
ra
al
r aw
ag

(Major ionic form

|

of acid excretion)
w
ro
ar
M
©

α cell β cell
Etiology :

Inherited (M/c) : Acquired :

• AR : Sjögren’s syndrome.
H+ ATPase/H+-K+ ATPase defect (M/c).
• AD : Anion exchanger defect.

Note :
Carbonic anhydrase type 2 defect (Previously type 3 RTA) :
• Calcification. • Short stature.
• Osteopetrosis.

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 230 Medicine

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

H+ ATPase/H+-K+ ATPase defect

Inability to acidify urine :

Urinary pH > 5.5

Alkaline urine + H+ retention

Severe NAGMA

↑Ca2+ resorption from bone ↓Fluid resorption in PCT

2O RAAS activation
Rickets. Hypercalciuria :
• Urinary stones. Severe hypokalemia :

om
• Medullary nephrocalcinosis. Hypokalemic paralysis.

l.c
Type 1 vs. Type 2 RTA :

ai
gm
Type 1 RTA/distal@ Type 2 RTA/proximal
56
t4

Hypokalemia Severe Mild

hi

NAGMA Severe Mild

c
ra
al

Urine pH ↑ N
aw

Renal rickets D/t Ca loss Severe : D/t phosphaturia

r

2+
ag

Glycosuria - +
|
w
ro

RFT N N
ar
M
©

Type 4 RTA 00:24:53

AKA hypoaldosteronism.

P Cells Of Collecting Duct :

MR : Mineralocorticoid receptor.
AIP : Aldosterone induced proteins.
ENaC : Epithelial Na+ channel.

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 Tubular Disorders 231

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

Acquired > Inherited.

True hypoaldosteronism Pseudo hypoaldosteronism
(Absent receptor binding)

Hyporeninemic : Hyperreninemic : Inherited : Acquired (M/c) :

Chronic tubulo-interstitial
• Drugs : β blocker, NSAID. • Addison’s disease • Type 1.
• Drugs : • Type 2 disease (CTID) :
• DM :
- - ACEi. (Gordon syndrome) : • Drugs :
- Prorenin Renin.
- ARBs. - Young onset. - Lithium.
- Autonomic neuropathy
- Aldosterone synthase - Hyperkalemia. - PPI.
(β1 dysfunction).
inhibitor : - ↑BP. - Calcineurin inhibitor.
Heparin, ketoconazole. • Toxins : Lead, cadmium.
• CKDu (Unknown etiology).

om
• Oxalate (Obstruction).

l.c
• Uric acid.

ai
gm
• Hypercalcemia &
@ Hypokalemia.
56
• Reflux nephropathy.
t4

• Autoimmune :
chi

- Sarcoidosis.
ra
al

- Sjögren.
aw

Note : - IgG4.
r
ag

Clinical presentation of CTID :

|
w
ro
ar

- Aldosterone binding - ADH binding : Nephrogenic DI/AVP-r - Erythropoietin

M
©

Type IV RTA Water diuresis : Anemia.

• Polyuria. • Nocturia.
Hyperkalemia. • Polydipsia.

Bartter Syndrome 00:36:00

Thick Ascending Limb of LOH :

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 232 Medicine

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

AR inheritance :
Type Defect Survival in adulthood
1 (M/c) Na+-K+-2Cl- symporter -
2 ROMK -
3 (Classical) ClCKB +
4 Barttin ( + in perilymph deafness) -
5 (AD) Ca2+ sensing receptor (Gain of function) -

Clinical Presentation :
Na+-K+-2Cl- defect

om
Loss of Na+, K+, Cl- (↑U. osmolarity)

l.c
Defective ADH binding

ai
Loss of H2o

gm
@
56
• N /↓BP + 20 RAAS :
t4

• Salt wasting
hi

• • Hypokalemia.
c

Polyuria.
ra

• Failure to thrive. • Alkalosis.

al
raw
ag

• Hypercalciuria : Urinary stones.

|

• Hypermagnesuria 20% Hypomagnesemia.

w
ro
ar
M
©

Gitelman Syndrome 00:41:20

Defect in Na+-Cl- symporter on distal convoluted tubules.

DCT

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 Tubular Disorders 233

Gitelman Vs Bartter Syndrome : ----- Active space -----

Gitelman Bartter
Inheritance AR AR (Type 5 : AD)
Survival to adulthood + Only in Type 3
Salt wasting Mild ↑
Polyuria Mild ↑
2 RAAS activation
o
Mild ↑
Hypokalemia Mild ↑
Alkalosis Mild ↑
Urinary calcium Hypocalciuria Hypercalciuria (> 4 mg/kg/24hrs)
+ : D/t ↓Mg2+ absorption
Hypomagnesemia Only in 20%
(Defective TRPM-6 in Intestine)
BP N /↓ N /↓

om
RFT N N

l.c
ai
gm
Hypo & Hyperkalemia @ 00:45:25
56
t4

Hyperkalemia Hypokalemia
chi

(<2meq/L)
ra
al
aw

Abnormal RFT N RFT/Disproportionately ↑K+

r

Renal loss Non-renal loss :

ag

Renal failure. Type 4 RTA. (↑Urine K+ : Cr) • Insulin.

|
w

• β2 agonists.
ro
ar

ABG
M
©

Acidosis Alkalosis

NAGMA
N /↓BP : ↑BP :
• Bartter. • Conn’s
Type 1 RTA : Type 2 RTA. • Gitelman. • Cushing’s Acquired.
• ↑Urinary pH. • Liddle’s
• N Fractional excretion • AME Inherited.
of phosphorus. • GRA

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 234 Medicine

----- Active space ----- GLOMERULAR DISORDERS

Structure of Glomerulus :
Bowman’s space : B/w parietal & visceral epithelium.

Layers of filtration barrier :

1. Capillary endothelium : Made up of
fenestrations.
2. Glomerular basement
membrane (GBM) Seen on EM Normal glomerulus
3. Slit b/w podocytes

om
Supporting cell : Mesangial cells.

l.c
ai
gm
Clinical Presentation 00:01:58
@
56
t4
chi
ra

Asymptomatic Hematuria Nephrotic Acute Rapidly

al
aw

Syndrome (NS) glomerulonephritis progressive

r
ag

(AGN) glomerulonephritis
|

(RPGN)
w
ro

Asymptomatic :
ar
M

Diagnosis :
©

Screening URE :
• Urine albumin : 3 +
• RBC : +

Confirmatory Test :
• Significant Proteinuria (> 500 mg/24h)/
Albuminuria (> 300 mg/24h)
• Microhematuria : ≥ 3 RBC/hpf

Biopsy :

FSGS IgA nephropathy Membranous nephropathy (MN)

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 Glomerular Disorders 235

Hematuria : ----- Active space -----

Etiology :

Urological (90%) : Renal (9%) Hematological

m/c : Bladder cancer (1%) : Hemolysis
Symptoms :
• Intermittent high colored urine.
• H/o respiratory infection.

Diagnosis : Dipstick Test : +ve

Centrifugation :
Supernatant

om
l.c
ai
gm
Clear Still high coloured
@
56
t4

RBC Morphology
hi

Hemoglobin Myoglobin
c
ra
al
r aw
ag

Dysmorphic RBC Acanthocytes (5%) : RBC cast (1%)

|
w

(40%) Mickey mouse RBC

ro
ar
M

Glomerular Hematuria
©

Biopsy : IgA nephropathy

Nephrotic Syndrome (NS) 00:09:42

Presentation :
Subacute onset.
Edema : Extravascular.
Proteinuria with nil RBCs : Nephrotic range (> 3.5g/24hrs).
Hypoalbuminemia.

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 236 Medicine

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

Thrombosis : D/t loss of AT-III protein & Protein C, S.
Dyslipidemia :
• ↑Cholesterol More common in adult onset NS
• ↑TG
• ↑LDL
• ↓HDL

Etiology :

Childhood NS : Adult onset NS :

Minimal change disease (90-95%) :
Podocytopathy without podocytopenia  No risk < 60yrs : > 60yrs :
for CKD • 1° FSGS > MN MN (M/c)

om
• AA Amyloidosis

l.c
ai
Management of Childhood NS :
gm
Prednisolone (2mg/kg or 60mg/m2/day) x 6 weeks @ Taper over 6 weeks
56
t4
hi

12w
c
ra
al

Response to steroids :
raw
ag
|

Response to
w

Outcomes Further Rx
ro

steroids
ar
M

25% : Recovery -
©

25% : Infrequent
Steroids during episodes
relapses
Remission
Urine albumin : Steroid sparing therapy :
Nil x 3 days FRNS • Cyclophosphamide
50% • Rituximab
• MMF
SDNS
• Rituximab
Biopsy : Genetic FSGS Rx : Transplant
• Podocin related (AR)
Resistance SRNS • α-actinin TRPC6 (AD)
No FSGS Steroid resistant MCD :
Rx with calcineurin inhibitors

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 Glomerular Disorders 237

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

• SRNS (Steroid resistant nephrotic syndrome) : No response with 4w of steroids.
• FRNS (Frequently relapsing nephrotic syndrome) : ≥ 2 relapses in 6 months/≥ 4
relapses in 1 year.
• SDNS (Steroid dependent nephrotic syndrome) : ≥ 2 relapses within 2 weeks of
stopping/tapering dose of steroids.

Acute Glomerulonephritis (GN) 00:19:15

AKA Nephritic syndrome.

PSGN vs IRGN :

Post streptococcal GN (PSGN) Infection related GN (IRGN)

om
Adults :
Boys (2-7y) :

l.c
Seen in • Immunosuppressed

ai
Immunocompetent

gm
• DM
@
Group A β-hemolytic
56
Etiology MRSA
t4

streptococci
chi
ra

Predisposition Skin > Throat infection Diabetic cellulitis

al
aw

Skin infection : 3 - 6 weeks

Incubation Period -
r
ag

Throat infection : 1 - 3 weeks

|

• High colored urine

w
ro

• Hypertension
ar

Presentation -
M

• Mild renal failure

©

• Intravascular edema
Prognosis Good Poor (RPRF-RPGN)
• Control BP
• Maintain K+
Management -
• Maintain intravascular
volume
C3↓ 8 weeks Normal C3
Ix -
C3↓ Biopsy
Immunofluorescence Starry Sky (IgG) -
Bx DPGN (diffuse proliferative) -

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 238 Medicine

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

Starry sky pattern

Nephrotic vs Nephritic Syndrome :
Nephrotic Nephritic
Onset Insidious Abrupt
Edema ++++ ++

om
BP Normal ↑

l.c
JVP Normal/↓ ↑

ai
gm
Proteinuria ++++ ++
@
56
Hematuria ± +++
t4

- +
hi

Red cell casts

c
ra

S. albumin Normal/slight ↓
al

↓
aw

Podocytopathy
r

00:22:40
ag
|
w

MCD FSGS MN
ro
ar

75% : NS 70% : NS
M

Presentation 100% : NS
©

25% : Asymptomatic 30% : Asymptomatic

0% (No Untreated : 33%
CKD progression 66%
podocytopenia) Treated : 15%
2° Nephrotic proteinuria only : • 1°:
• 1°:
• Hyperfiltration injury : PLA2 R Ab
Children :
Adaptive response post U/L (Phospholipase A2 receptor
D/t Allergy
nephrectomy antibody test)
• 2°:
Etiology • HIV • 2°:
- NSAIDs
• Parvovirus B19 - HBV
- IFN α
• Obesity - SLE
- Hodgkin’s
• Heroin - Malignancy (Colorectal Ca)
lymphoma
• Pamidronate - Mercury
• Thickening of GBM
Biopsy Normal Focal & segmental sclerosis
• IgG ± C3 deposits

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 Glomerular Disorders 239

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

FSGS MN
Glomerulonephropathy 00:27:10

Membranoproliferative GN IgA nephropathy

• > 50% : Hematuria with h/o
• 35% : NS infection

om
• 35% : Acute GN • HSP adults : IgA vasculitis +
Presentation

l.c
• 20% : CKD RPGN

ai
gm
• 10% : RPGN • < 5% : NS
@
• Asymptomatic
56
t4

• GBM Thickening
chi

• Proliferation +
ra
al
aw

- Endocapillary
• Mesangial Proliferation
r
ag

Biopsy - Mesangial
• IgA deposits
|

• Capillary tuft : Globular appearance

w
ro

• Nodules +
ar
M

• Double contour tram track appearance

©

Monoclonal Pattern Polyclonal Pattern

• HCV
• Leprosy
• Infective
endocarditis
• Malaria 1/3 : Recover 1/3 : Stable
• Plasma cell
Key points • Cryoglobulinemia
disorders
• C3 GN : 1/3 : Progress
• C3 GN
- Optic nerve to CKD
drusen
- Acquired partial
lipodystrophy of
face

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 240 Medicine

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

Drusens Cryoglobulinemia IgA nephropathy

RPGN 00:30:42

RPRF with glomerular cause

om
Presentation :

l.c
> 2 weeks of RPRF features :

ai
gm
• Edema : ++ • Hematuria with ↓output.
@
• Uremic features : Breath, • Hypertension.
56
t4

pericarditis, gastritis.
chi
ra
al

Investigations :
raw

Labs :
ag

• ↑S. Cr.
|

• ↑U. albumin (3+).

w
ro

• ↑S. BUN. • ↑S. K+.

ar
M

Light microscopy :
©

• Crescents.
RPGN
• DPGN.
Immunofluorescence (IF) :
Types Type 1 Type 2 Type 3
IF Linear IgG + C3 Immune Complex Pauci-immune
• SLE
Goodpasture
Diseases • Adult HSP ANCA associated
syndrome
• IRGN

• Diffuse alveolar hemorrhage

• Ab against α3 chain of type IV collagen
• Rx : Plasma exchange therapy
Rx :
• Steroids. • Cyclophosphamide.

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 Acute kidney injury (AKI) Rapidly progressive renal failure Chronic kidney disease (CKD) :
(Hours to days) : (Days to weeks) : • Diabetes mellitus.
• Rapidly progressive • Chronic
URE
Normal Abnormal glomerulonephritis (RPGN). glomerulonephritis.
• Vascular causes : • Ischemic nephropathy.
Pre renal : Post renal - Thrombotic • Chronic tubulointerstitial
Volume depletion : (USG : microangiopathy (TMA). nephritis.
• Diarrhea. Hydroureteronephrosis). © - B/L renal artery
• Vomiting. M stenosis (RAS).
• Polyuria.
ar • Severe AIN.
ro
• Diuretics overuse. w
• Diabetes insipidus. Acute tubular Acute interstitial
| nephritis
a
• Hypoalbuminemia . necrosis (AIN) : gr
(ATN) aw
(Hypersensitivity response
al
ra
Interstitial inflammation) ch
it4
Ischemic : Toxin 56
• Volume loss. @
• Sepsis. Drugs. :
Infectiongm Infiltration :
• Sarcoidosis.
ACUTE KIDNEY INJURY

[Link]
.c

Medicine • World of Revision • v2.0 • Marrow • 2025

om • Lymphoma.
Endogenous : Exogenous :
APPROACH TO RENAL FAILURE &

• Hemolysis (Hb). • Drugs.

• Tumor lysis syndrome • Contrast.
(Uric acid).
• Rhabdomyolysis
(Myoglobin).
Approach to Renal Failure and Acute Kidney Injury

• Light chain myeloma

(Light chain).
241

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

 242 Medicine

----- Active space ----- Secondary Hypertension 00:06:55

Presentation :
• Young age.
• Hypertension.
• Target organ damage : Disproportionate to HTN
- LVH.
- Retinopathy.
- Microalbuminuria.

Etiology :

Renal causes Endocrine causes :

om
• Conn’s syndrome.

l.c
• Pheochromocytoma.

ai
Glomerular : Vascular : • Acromegaly.

gm
• USG : • USG : • Inherited : Liddle’s,
@
56
- Partially lost CMD - CMD preserved Gordon’s syndrome.
t4

- Small kidneys - Asymmetric kidneys • Hyperparathyroidism.

hi

• Proteinuria : 2 - 3 + • Proteinuria : 1 + • Thyrotoxicosis.

c
ra

• ↑U. RBCs • - RBCs

al
raw
ag

Biopsy : RFT
|

CGN - IgA nephropathy

w
ro

Normal : ↑ : B/L RAS.

ar

CKD.
M

U/L RAS.
©

Vascular Kidney Disease 00:14:24

Renal Artery Stenosis :

Large vessel disease.
Etiology :
Atherosclerosis (M/c) Fibromuscular dysplasia (FMD) Takayasu arteritis
Age Elderly Young
Involves Proximal renal artery Mid-distal renal artery
• Arteriopathy
• H/o smoking
• Inflammation : - -
Key points • A/w peripheral occlusive vascular
• Rx : Renal angioplasty
disease
• Angiogram : String of beads

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 Approach to Renal Failure and Acute Kidney Injury 243

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

U/L RAS B/L RAS

• Hypertension • Flash pulmonary edema
Findings
• Asymmetric kidneys • Renal impairment
Salt & water ↑Excretion (Pressure natriuresis) ↑Retention (Intravascular)
• ACE -
• Diuretics
Rx • Percutaneous, transluminal renal
• C/i : ACE -
angioplasty with stenting (> 8 cm)

Evaluation :
• Screening test : Renal artery doppler.
• CT renal angiogram (CTRA).
• MR renal angiogram : PAN.

om
l.c
ai
gm
@
56
t4
chi
ra
al
r aw
ag
|

CTRA Angiogram FMD : String of beads

w
ro
ar

Thrombotic Microangiopathy (TMA) :

M
©

• AKA complement mediated TMA.

• Factor H mutation Alternate complement pathway activation.

Etiology :

Hemolytic uremic APS. Scleroderma Malignant HELLP

syndrome. renal crisis. hypertension. syndrome.

Presentation :
• Hypertension.
• Fragmentation hemolysis.
• Blood : Schistocyte.
• MAHA with thrombocytopenia.

Rx : Plasma exchange therapy.

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 244 Medicine

----- Active space ----- Pre-renal AKI vs ATN 00:24:34

Pre-renal AKI ATN

URE Normal Abnormal
BUN : Creatinine > 20 : 1 -
Urine Na+ ↓ ↑
Urine creatinine ↑ ↓
Plasma creatinine ↓ ↑
Fe Na < 1% > 2%
Fluids Mainstay of Rx Restricted

U. Na+ P. Creatinine × 100

Fractional excretion of Na+ (Fe Na) = U. Creatinine × P. Na+

om
l.c
ai
gm
Drugs Causing AKI @ 00:31:00
56
t4
hi

Tubular injury AIN : Interstitial inflammation Acute intratubular obstruction

c
ra
al

(Dose dependent) (Dose independent) (Dose dependent)

aw

Mnemonic : V BRAND
r
ag

Mnemonic : ACES
• Vancomycin Mnemonic : MITAS
|

• Aminoglycosides
w
ro

• β-lactams • Methotrexate
• Amphotericin B
ar

• Rifampicin • Indinavir
M

• Cisplatin
©

• Allopurinol • Triamterene
• Cidofovir
• NSAIDs • Acyclovir
• Ethylene glycol
• Diuretics • Sulfonamides
• Salicylates
• PPIs

Note :
• NSAIDs
Have strong pre-renal
• Contrast induced AKI
component.
• Rhabdomyolysis

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 Connective Tissue Diseases : Part 1 245

CONNECTIVE TISSUE DISEASES : PART 1 ----- Active space -----

Multisystem autoimmune inflammatory connective tissue diseases (CTDs) :

• Rheumatoid arthritis (RA) : M/c.
• Sjogren’s Syndrome : 2nd M/c.
• SLE.
• Scleroderma/systemic sclerosis (SSc).
• Polymyositis
Idiopathic inflammatory myopathies
• Dermatomyositis
• Overlap syndrome (≥2 CTD features) :
Mixed connective tissue disease (MCTD) : Anti-U1RNP Ab + .

om
Sjogren’s Syndrome

l.c
00:03:30

ai
gm
Features : 56
@
Age : Middle aged (40-60 yrs).
t4
hi

F:M=9:1
c
ra

Manifestations : 50% Glandular

al
aw

50% Extraglandular (15% severe)

r
ag
|

Associations : Hepatitis C virus (HCV).

w
ro

Types : Primary
ar
M

Secondary : Associated with other CTDs

©

• RA (M/c).
• SLE.
• Inflammatory muscle disease.
• Limited systemic sclerosis.

Note :
• Other conditions with F : M of 9 : 1 : • Other Extrahepatic manifestations of
- SLE HCV :
- Takayasu arteritis - Lichen planus
- Fibromyalgia - Porphyria cutanea tarda
- Chronic fatigue syndrome - Cryoglobulinemia
- Primary biliary cirrhosis - Membranoproliferative
glomerulonephritis (MPGN)

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 246 Medicine

----- Active space ----- Etiopathogenesis :

Exocrinopathy involving single endocrine organ (Thyroid).

Pathology :
Focal lymphocytic infiltration (CD4+ T cells)

Periductal + perivascular inflammation

Activation of ductal epithelium

Immune destruction Immune inhibition : Inhibition of M3

muscarinic receptors
(Rx of dry mouth : Cevimeline

om
(M3 agonist)).

l.c
ai
Etiology :
gm
@
56
t4

Genetic : HLA DR3 Environmental (No role for viral infection)

chi
ra
al
aw

T cell > B cell

r
ag

activation
|
w
ro

Th1 > Th17 Antibodies :

ar
M

• Anti Ro/La
©

• IL-2 • RF +ve
• IFN-γ • Cryoglobulins
• IL-18. • Anti-M3
• Anti alpha fodrin.
Note :
• Cytomegalovirus (CMV) : AKA Salivary gland virus (But not associated with
sjogren’s).
• Rheumatoid factor (RF) +ve :
- RA
- Sjogren
- Cryoglobulinemia

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 Connective Tissue Diseases : Part 1 247

Glandular Sjogren Manifestations : ----- Active space -----

Symptoms :
• Hallmark : Dryness.
• M/c : Fatigue.

1. Dry eyes/keratoconjunctivitis sicca :

• Affects all 3 layers of tear film (Most affected : Aqueous).
• Symptoms : Burning, Grittiness, ↑tears.
• Slit lamp examination :
- Lissamine green : Stains epithelial surface lacking mucin.
- Fluorescein dye : Stains devitalized cells/epithelial defects.
• Tear film break up time : < 10 secs.
• Schirmer’s test : < 10mm/5 min.

om
2. Dry mouth/xerostomia :

l.c
ai
• Specific.
gm
• Symptoms : @
56

- Recurrent dental caries : Specifically incisors.

t4
hi

- Difficulty in swallowing without water.

c
ra
al

- Recurrent oral thrush.

aw

- Dry atrophic tongue : Loss of papillae + fissured tongue.

r
ag

- Altered taste.
|
w
ro

3. Dry skin : Pruritis.

ar

4. Dry throat : Cough.

M
©

5. Dry GIT : ↓Exocrine Pancreas secretions.

6. Dry vagina.
7. Salivary gland swelling :
• Seen in 2/3rd of patients.
• M/C : Parotid gland.
- A/w low IL-18 +ve macrophages.
• Intermittent/chronic.
• Painless.

Note :
Tear film layers :
Layer Secreted by Clinical condition
Lipid Meibomian gland Blepharitis
Aqueous Lacrimal gland Sjogren’s
Mucin Goblet cells Stevens-Johnsons Syndrome (SJS)

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 248 Medicine

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

Xerostomia with dental caries Fissured tongue with loss of papillae Bilateral symmetric parotid swelling
8. Extranodal marginal zone B-cell lymphoma :
• Highest risk of transformation to malignancy among CTDs : Sjogren’s.
• M/c : MALToma of parotid gland (Overall M/c : Stomach).
• R/f (Suspicion of lymphoma in Sjogren’s) :
- Clinical : Rapid ↑in size/persistent/asymmetrical/nodular swelling.

om
- Serological :

l.c
ai
• ↑Titres of RF, Ro/La
gm
Also ↑risk of extraglandular Sjogren
• Cryoglobulins +ve @
56
(↓ C3 & C4)
• Low complement levels : ↓ C4
t4
hi

• Leukopenia
c
ra
al

- Histopathologic : Heavy focal lymphocytic infiltrates/germinal center

aw

formation.
r
ag
|
w

Extraglandular Sjogren Manifestations

ro

00:27:31
ar
M

Organs/system Associated conditions Clinical presentation

©

• Similar to SLE
• Non-erosive (Jaccoud’s arthropathy)
Joints Arthralgia/arthritis : M/c
• Non-deforming > Deforming (D/t ligament
laxity)
Precede sicca symptoms in 1/3rd Critical limb
2° Raynaud’s phenomenon
ischemia
Blood vessels
Immune complex mediated small
Cutaneous palpable purpura (Hallmark)
vessel vasculitis
CNS Neuromyelitis optica Anti AQP4 Ab positive
Nervous
PNS Ganglionopathy
system Severe asymmetrical truncal sensory ataxia
(M/c) (Dorsal root ganglion)
ILD : NSIP (M/c) Ground glass opacities (GGO)
Lung Lymphocytic interstitial pneumonia
GGO + Thin-walled cyst + Nodules
(Specific subtype to Sjogren & HIV)
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 Connective Tissue Diseases : Part 1 249

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

Organs/system Associated conditions Clinical presentation

Liver HCV -
Autoimmune inflammatory destruction of intrahepatic
bile duct :
Biliary tract Primary biliary cholangitis
• Intrahepatic cholestasis
• Anti mitochondrial antibody (AMA)
Tubulo-Interstitial (M/c) : • Hypokalemic paralysis
Type 1 /distal RTA • Nephrocalcinosis
Renal A/w cryoglobulinemia (medium vessel
involved ulcers, mononeuritis multiplex)
Glomerular : MPGN
Bad prognosis
Note :

om
• 2° Raynaud’s phenomenon : • Ganglionopathy :

l.c
- SSc (M/c) - Anti-Hu Ab associated

ai
gm
- Antisynthetase syndrome paraneoplastic syndrome
@
56
- Sjogren’s syndrome - Sjogren’s
t4

- MCTD
chi
ra
al

Sjogren v/s SLE :

raw
ag

Association with SLE Sjogren

|
w

Anti-phospholipid antibody (APLA) syndrome ↑R/o thrombosis + -

ro
ar

+ -
M

Accelerated atherosclerosis ↑R/o MI

©

• CNS vasculitis Small

Vasculitis
• Mesenteric vasculitis vessel
Glomerular disease Severe form + +/-

Investigations :
ANA :
• Screening test for CTDs.
• Method : Indirect immunofluorescence (IIF) by Hep-2 cell line.
• Titre : > 1 : 80.
• Pattern :
- Fine speckled : Anti Ro 60
Sjogren Metaphase
- Cytoplasmic : Anti Ro 52
cell
- Dense fine speckled pattern :
Rules out CTD.
Dense Fine Speckled (DFS) Pattern
Medicine • World of Revision • v2.0 • Marrow • 2025
 250 Medicine

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

Note :
ANA +ve % :
• SLE : 97% • MCTD
• Scleroderma : 95% • Drug induced lupus
100%
• Sjogren’s : 85% Erythematosus (DILE)
• Type 1 autoimmune hepatitis
Anti Ro/La Antibodies :
1˚Sjogren 2˚Sjogren
Anti-Ro 52 +ve +ve
Anti-Ro 60 +ve -ve

• Significance of ↑Ro/La titres :

- ↑Disease activity.

om
- Poor prognosis.

l.c
- Early onset & longer disease duration.

ai
gm
- Salivary gland enlargement.
• In 2° Sjogren : @
56
t4

- Good prognosis : ↓R/o nephritis/vasculitis.

chi

- ↑R/o Neonatal lupus with congenital heart block (2-5%) : SLE > Sjogren.
ra
al
aw

Biopsy :
r
ag

• Lip/minor salivary gland :

|
w

- Gold standard for Sjogren Dx.

ro
ar

- Focal CD4+ T-lymphocytic sialadenitis.

M
©

• Major salivary glands :

B cells infiltrate Benign lymphoepithelial lesions.

Sialography : Unstimulated salivary flow rate < 1.5ml/15mins.

Management :
• Steroids : Mainstay Rx (Sicca symptoms : Unresponsive to steroids).
• Lubricants : If ↓secretions.
• Low dose steroids + HCQ + NSAIDs : Glandular symptoms with fatigue/arthralgia.
• Mycophenolate mofetil (MMF) : Systemic manifestations (ILD).

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 Connective Tissue Diseases : Part 2 251

CONNECTIVE TISSUE DISEASES : PART 2 ----- Active space -----

IgG4 Related Diseases 00:00:16

IgG4 Properties :
• Least common type of IgG (< 5%)
• Complement binding -
• Fab arm exchange Bispecific Ab.
• Inhibits IgG1 & C1q interaction : Anti-inflammatory.

Histopathology :

om
• Lymphoplasmacytic TGF-β Storiform fibrosis
Activate myofibroblast

l.c
cells (Contain IgG4) (Fibrogenic)

ai
gm
• Obliterative phlebitis (Also seen in Bechets).
@
• Mild Eosinophilia.
56
t4
chi
ra
al
r aw
ag
|
w
ro
ar
M
©

Lymphoplasmacytic infiltrate Storiform fibrosis + Cartwheel pattern Obliterative phlebitis

Clinical Presentation :
• Age : 40-70 yrs
Elderly male predominant
• M>F
• H/o Atopy.
• Tumefactive lesions (Tumor like).
• Subacute onset : Weight loss, fatigue, myalgia.
• Lymphadenopathy + .
• Sicca symptoms :
- Minimal/ - .
- Responsive to steroids.

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 252 Medicine

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

Clinical manifestations :

Organs/
Associated conditions
system
IgG4/Type 1 autoimmune pancreatitis (M/c manifestation) :
• Obstructive jaundice with sausage shaped pancreas (M/c)
GIT • Type 3c diabetes mellitus
• Exocrine pancreatic insufficiency
• ERCP : Diffuse irregular narrowing of pancreatic duct
• Pachymeningitis (Brain parenchyma spared)
CNS
• Lymphocytic hypophysitis
Eyes Inflammatory pseudotumors
• Submandibular sialadenitis (Most classical manifestation) : B/L Symmetric painless swelling.
• Mikulicz syndrome :
Salivary gland

om
- Salivary : Submandibular, parotid

l.c
- Lacrimal : Dacryoadenitis

ai
gm
Thyroid Riedel’s thyroiditis
@
Lungs ILD (NSIP) : Lower lobe (Thickening of broncho-vascular bundles)
56
t4

Vasculitis Aortitis (M/c) + Para-vertebral mass

chi
ra

IgG4 related sclerosing cholangitis (AKA primary sclerosing cholangitis ) :

al

Biliary tract
aw

Fibrosing destruction of intra & extra hepatic bile ducts.

r
ag

• Tubulointerstitial nephritis (M/C) : Cured on steroids.

|

Renal • Glomerular : Membranous nephropathy (MN)

w
ro

• Ormond’s disease : Idiopathic retroperitoneal fibrosis (Obstructive nephropathy & AKI)

ar
M

: Now considered as IgG4 related disease

©

Orbital/Lacrimal gland swelling Sausage pancreas

Management :
Steroids : 1st line
Rituximab : Relapse

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 Connective Tissue Diseases : Part 2 253

Sarcoidosis 00:16:14 ----- Active space -----

• Multisystem inflammatory granulomatous condition (Non-caseating granulomas)

• Age : > 18 yrs.
• M = F.

Etiopathogenesis :
Genetics : 03 : Lofgren syndrome (Good prognosis)
• HLA : DRB1 04 : Protective (Associated with RA)
11 : CNS & cardiac sarcoidosis (Bad prognosis)

• NOD2 Gene mutation : Blau Syndrome (Childhood prototype).

R/F :

om
• Propionibacterium acnes.

l.c
• Burning fire wood.

ai
gm
Immune paradox : @
56
t4

• ↑Lymphocytes Utilized in granuloma formation Lymphopenia (In blood).

chi

• False negative Mantoux test.

ra
al
aw

Course of Disease :
r
ag

• 50% : Spontaneous resolution (Acute : No Rx).

|
w

• 25% : Chronicity (Lung, skin, eyes, joints).

ro
ar

• 5% : Mortality (D/t ILD).

M
©

Acute Sarcoidosis Manifestations :

Good Prognosis.

Lofgren Syndrome :
• Acute onset fever.
• B/L Hilar adenopathy.
• B/L Ankle joint tenosynovitis. Garland’s sign :
• Erythema nodosum : B/L hilar adenopathy + R paratracheal nodes
- Painful
- Pre-tibial
- Papule
- Non-pigmented
- Panniculitis on biopsy
Erythema nodosum

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 254 Medicine

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

Heerfordt Waldenstrom Syndrome :
• Acute anterior uveitis.
• B/L Parotitis.
• B/L LMN 7th CN Palsy (M/c CNS manifestation).

Notes :
Other rheumatological disorders presenting with fever : Antisynthetase syndrome.

Chronic Sarcoidosis Manifestations :

Organs/System Associated conditions
• B/L LMN 7 nerve palsy (M/c)
th

• Infiltrative stalk lesion : Cranial DI/AVP deficiency

CNS
• Meningeal enhancement
• Acute transverse myelitis (ATM) of spine

om
l.c
B/L Panuveitis + Retinal vasculitis :

ai
Eyes • Anterior > Posterior

gm
• Keratic precipitates + @
56
B/L Upper lobe ILD (M/c : NSIP) :
t4
hi

Lung • Thickening of bronchovascular bundle

c
ra

• Perilymphatic nodules
al
aw

• Dilated (DCM) > Restricted (RCM) cardiomyopathy

Heart
r
ag

• Conduction block : D/t interference by granulomas

|
w

Liver Intrahepatic cholestasis : ↑Alkaline phosphatase (ALP)

ro
ar

Renal Tubulointerstitial (Rare or no glomerular involvement)

M
©

Spleen Splenomegaly ± Pancytopenia

Lupus pernio : Chronic inflammatory skin lesion on face

Skin • Maculopapular lesion
• Nodular infiltrative lesion

• Dactylitis : Single finger inflamed/sausage digit

Bones and joints • Bone cyst
• ↓Bone marrow density : Fractures

Granuloma producing 1-α hydroxylase

↑1,25 Dihydroxy cholecalciferol

Endocrine ↑Ca2+, ↑phosphorus

Hypercalcemia Hypercalciuria

Nephrogenic DI Nephrocalcinosis
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 Connective Tissue Diseases : Part 2 255

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

• Other condition with upper lobe ILD :
Ankylosing spondylitis
• Dactylitis : m/c in Spondyloarthritis
(Reactive/psoriatic arthritis)

Least likely presentations in sarcoid :

Conditions Seen in
Pleural effusion SLE, RA
Lungs Subpleural Usual
honeycombing interstitial pneumonia
Eyes Episcleritis RA
Renal Glomerulonephritis Lupus pernio

om
Laboratory Anti-Neutrophil cytoplasm antibody (ANCA) +ve

l.c
ai
gm
Investigations : @
56

Chest X-ray : Scadding scoring system

t4
chi
ra
al
r aw
ag
|
w
ro
ar
M
©

Stage 1 : Hilar adenopathy Stage 2 : ↓Lymph node size, Stage 3 : ↑↑Parenchymal Stage 4 : Fibrosis
↑Parenchymal infiltrates infiltrates
Clinical paradox : Inspite of ↓LN size, patient condition worsens.

ACE levels :
• N : Rules out Sarcoidosis.
• ↑ : Non-specific marker.
Ga-67 Scintigraphy : Panda sign
(B/L lacrimal gland, Parotid & normal
nasopharyngeal uptake).
PET scan : Preferred to detect nodes CT scan : Thickened bronchovascular
F/b bundles, Perilymphatic micronodules Panda sign
EBUS guided transbronchial biopsy. distribution
BAL : CD4/CD8 ratio > 2 : 1

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 256 Medicine

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

Note :
CD8 > CD4 : Hypersensitivity pneumonitis

Management :
Acute : No Rx required Self resolving.
Chronic :
• Steroids : 1st line.
• Methotrexate, Azathioprine : 2nd line.
• Anti TNF-α : 3rd line.
- Infliximab.
- Adalimumab.
- Etanercept :
• Indication : Expected latent TB reactivation.

om
• C/I : Uveitis & colitis.

l.c
ai
Behcet’s Disease
gm
00:39:00
@
56
• Chronic relapsing autoimmune multisystem disease.
t4
hi

• Variable vessel vasculitis : M/c large vessels (Venous > Arterial).

c
ra

• Age : 3rd & 4th decade.

al
aw

• M = F (↑Severity : Young males).

r
ag
|

Etiopathogenesis :
w
ro

HLA : B51/B5 > A26, B27, B57

ar
M

Antibodies :
©

• Anti-saccharomyces cerevisiae antibody (ASCA).

• Anti-enolase antibody.
• Anti-Selenium binding protein antibody.

Note :
HLA B 52 : Takayasu arteritis
B27 : Ankylosing spondylitis (Sp A).

Pathogenesis :
• T-cells + neutrophils mediated.
• Neutrophilic dermatoses with panniculitis (Vascular reaction + ) without
granuloma.

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 Connective Tissue Diseases : Part 2 257

Clinical Manifestations : ----- Active space -----

1 Major + 2 Minor.

Major manifestations :
Oral cavity lesion :
• Recurrent (≥ 3 times/yr). • Painful.
• Papule Shallow ulcer with • Heals without scarring.
pseudomembranous necrotic base.

Note :
SLE : Painless ulcer over hard palate.

Minor Manifestations :

om
Manifestation Characteristics

l.c
• Neutrophilic vascular reactions

ai
gm
• M/c : Papulopustular lesions 56
@
• Association : Erythema nodosum
t4

Cutaneous
hi

- Painful
c

lesions
ra

- Pretibial
al

(Seen in 80%)
aw

- Pigmented
r
ag

- Papule
|
w

- Panniculitis
ro
ar

• Chronic relapsing B/L panuveitis (Posterior > Anterior) + Retinal vasculitis

M

Eye (M > F)
• Hypopyon +
©

• M/c : Scrotum/labia
• Spares : Glans penis/urethra
• ↑Painful & deeper
Genital ulcer
• ↓Recurrence
• Heal with scarring
• 5% : Extragenital Buttock/anogenital.
• Aim : To check hypersensitivity reaction
• Procedure : Oblique skin puncture with 25-gauge needle Read after 1-2
Pathergy test days
• Positive test : Papule/pustule with erythema
• Low sensitivity (60%)

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 258 Medicine

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

Other manifestations :
Organs/System Associated conditions
CNS Brain parenchyma involved (IL-6 mediated) : Limbic/brainstem encephalitis
• Pulmonary artery aneurysms (M/c)
Blood vessels • Vascular thrombosis Superficial + Deep vein thrombosis Immunosuppression
Arterial thrombosis not indicated to Rx
GIT Similar to Crohn’s disease
Joints Arthritis (Similar to spondyloarthritis)
Organs spared : Lungs, kidney, heart

Note :
Pulmonary artery aneurysms : Also in Takayasu.

om
l.c
ai
gm
@
56
t4
chi
ra

Oral aphthous Ulcers

al

Genital ulcers
raw

Sweet syndrome : Febrile neutrophilic dermatoses.

ag

MAGIC syndrome : Mouth and genital ulcers with

|
w
ro

inflamed cartilage (Bechet’s + Relapsing

ar
M

polychondritis).
©

Management :
• Topical steroids : 1st line.
Sweet syndrome lesion
• Systemic steroids : Severe systemic manifestations.

Note :
Cogan’s Syndrome :
Non-Syphilitic Interstitial Keratitis

Occur within 2 yrs F/b Aortitis

Variable
vessel
vasculitis
Aortitis Vestibulitis (SNHL) :
Similar to Meniere’s disease

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 Rheumatology : RA and SLE 259

RHEUMATOLOGY : RHEUMATOID ARTHRITIS AND ----- Active space -----

SYSTEMIC LUPUS ERYTHEMATOSUS

Arthritis :

Erosive arthritis : Non-erosive arthritis :

• RA. • SLE.
• Chronic crystal arthropathies • Jaccoud’s arthropathy (SLE like arthropathy).
(Gout/pseudogout). • Sjögren.
• Psoriatic arthritis. • Polymyositis. Synthetase
• Rhupus (RA + SLE) : • Dermatomyositis. syndrome

om
Erosive arthritis in SLE. • Scleroderma.
• Acute rheumatic fever (ARF).

l.c
ai
• Acute crystal arthropathies.

gm
@
56
Pathogenesis of erosive arthritis :
t4

Synovitis Synovial Pannus Marginal erosion of bone.

chi
ra

(Articular pain : hypertrophy formation (Not covered by articular

al
aw

• Deep & diffuse cartilage)

r
ag

• ↑es on movement)
|
w
ro

Rheumatoid Arthritis (RA)

ar

00:03:28
M
©

• M/c multisystem autoimmune inflammatory CTD.

• F > M (3 : 1).
• Age : 40 - 60 yrs.

Joint Involvement :
Joints affected Joints spared
• Distal radioulnar junction (DRUJ)
• Wrist • DIP
Upper limb
• MCP • 1st CMC
• PIP
Lower limb 5th MTP 1st MTP
Spine C1 -C2 Thoracolumbar spine
• Cricoarytenoid Marginal erosions
Others -
• TMJ

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 260 Medicine

----- Active space ----- Pathogenesis :

Genetic factors : Environmental factors : Other factors :
• HLA DRB1-04 : • Smoking : • Protective : Pregnancy (↑IL-10)
QKRAA motif - ↑R/o ILD (M > F) • No risk :
• PADI-4 - ↑Expression of PADI-4 - Alcohol
• Porphyromonas gingivalis : - OCP
Chronic periodontitis
• Silica

Abnormal protein modifications

(Citrullination & carbamylation)

Dendritic cell uptake + T-cells

(Type IV hypersensitivity)

om
+
Immune complex (DC-T interaction) B-cells Antibodies.

l.c
ai
+

gm
Th1 Th17 @
56
t4
c hi
ra

Interferon (IFN) γ
al

+
aw

Macrophages
r
ag
|

TNF-α
w
ro

- +
ar
M
©

Osteoblast. Osteoclast.
(β-Catenin pathway) (RANK ligand–RANK interaction)

Clinical Presentation & Diagnosis :

• Polyarthritis :
- B/L symmetrical
- Small joint predominant
- Peripheral
• Articular pain
• ↑Inflammatory markers (ESR, CRP)
• Morning stiffness (> 45 mins) : ↓es with activity

< 6 wks > 6 wks (Chronic)

1/3 cases
Undifferentiated RA
arthritis

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 Rheumatology : RA and SLE 261

RA markers : ----- Active space -----

• Anti-CCP antibody (Specific).
• Rheumatoid factor (Non-specific) :
Also seen in : Markers for :
- Cryoglobulinemia. • Progression to RA.
- Sjögren. • Poor prognosis.
- JIA.
• Synovial fluid WBC count : Best marker to differentiate
inflammatory &
non-inflammatory.

Variants :
Rheumatic nodules
Palindromic rheumatism : Acute monoarthritis.

om
Acute explosive polyarthritis : In elderly.

l.c
Elderly RA : Mimic PMR.

ai
gm
Rheumatic nodules (Pure extraarticular) :
@
• ↑RF titres.
56
t4

• Painless.
chi
ra

• Type IV hypersensitivity reaction.

al
aw

• Granulomas + . Hitchhiker’s thumb

r
ag

• Methotrexate Rx : ↑Size in 10%.

|
w
ro

Deformities :
ar
M

Reversible deformities :
©

• Zig zag deformity :

- MCP joints : Radial deviation.
- Wrist : Ulnar deviation.
• Piano key deformity : Ulnar collateral ligament rupture
(Ulnar styloid deformity).
• Hitchhiker’s thumb : Opera glass
Abduction & hyperextension of thumb. deformity

True deformities : Cannot be reversed.

Boutonniere deformity Swan neck deformity Vaughan–Jackson deformity : Pointing index

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 262 Medicine

----- Active space ----- Systemic Lupus Erythematosus (SLE) 00:14:00

• F > M (9 : 1) in reproductive age group.

• Malignant forms : Early start (Younger age).

Variants :
SLE in males : Bad prognosis. Post menopausal SLE :
• ↓Anti-dsDNA.
Childhood SLE : Renal involvement + .
• Normal complement levels.
• Good prognosis.

Drug induced lupus erythematosus (DILE) :

• 100% ANA +ve.
• Anti-histone antibody +ve (Homogenous pattern).

om
• Spared : Renal, CNS.

l.c
• Drugs (Mnemonic : CHIMPP) :

ai
gm
- Carbamazepine. - Methyldopa.
56
@
- Hydralazine. - Procainamide.
t4
hi

- Isoniazid. - Propylthiouracil.
c
ra
al

Note :
raw

100% ANA +ve :

ag
|

• MCTD.
w
ro

• Type 1 autoimmune hepatitis.

ar
M
©

Pathogenesis :
Genetic factors : Environmental factors :
• C1q deficiency • Epstein Barr Virus (EBV)
• HLA DR2 < DR3 (More severe) • Estrogen : OCPs, HRT

↓Clearance of apoptotic/NETotic debris

+
Innate immune system : Plasmacytoid dendritic cells (pDC)
+ +
IFN α T-cells Th2 IL-4 B cells Antibodies

Form immune complex deposits :

(Type III hypersensitivity)
• Vessel : Vasculitis
• Glomerulus : Glomerulonephritis
• Joint : Synovitis

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 Rheumatology : RA and SLE 263

Cutaneous Manifestation : ----- Active space -----

Malar rash :
• Photosensitive.
• Erythematous.
• Scaly.
• Non-scarring.
• Sparing of naso-labial fold. Malar rash

om
Toxic epidermal necrolysis (TEN) Non scarring alopecia Male SLE

l.c
ai
gm
Lab Findings :
@
56
• Anti-C1q : Specific for lupus nephritis.
t4
hi

• ↓Soluble C3 & C4.

c
ra

• Anti-dsDNA titres : a disease activity.

al
r aw
ag

Systemic Manifestations of SLE and RA 00:19:40

|
w
ro

Organs/system SLE RA
ar
M

• Brain parenchyma involved

©

CNS • Cognitive dysfunction (M/c) : Brain parenchyma not involved

Anti-ribosomal P antibody (Specific)
Leukocytoclastic vasculitis
• Carpal tunnel syndrome :
PNS D/t synovium hypertrophy
Small fibre neuropathy
• C1-C2 myelopathy :
D/t atlantoaxial subluxation
• CNS vasculitis (Rx : Plasmapheresis) Muscular artery vasculitis (In deep reticular
Blood vessels
• Mesenteric vasculitis dermis) : Nodules, ulcers, gangrene
Anti-Ro/La ab :
• 2° Sjögren
• Good prognosis (↓Disease activity)
• 2° Sjögren (M/c)
• In pregnancy :
Eyes • Episcleritis
Neonatal lupus with complete heart block
• Scleritis Scleromalacia perforans
• A/w subacute cutaneous lupus erythematosus
(Photosensitive)
• Myocarditis (Anti-Ro ab.)

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 264 Medicine

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

Organs/system SLE RA
• Normocytic normochromic anemia (M/c) : Anemia of chronic disease
• 2° ITP
• Autoimmune hemolytic anemia : Warm antibodies
• ↑R/o DLBCL
Blood
• Felty syndrome (Neutropenia + splenomegaly) :
In longstanding RA
Leucopenia
• Large granular lymphocytic leukemia
(Benign with risk of AML conversion)
Classes :
• I : Minimal mesangial
• II : Mesangio- Asymptomatic
proliferative

om
• III : Focal lupus Proliferative GN • Usually spared (No GN)
• 2° amyloidosis (M/c)

l.c
Kidney nephritis (< 50%) (RPGN type 2)

ai
• 2° membranous nephropathy (Rare)

gm
• IV (M/c) : IF :
Diffuse lupus @
56
• Full house effect
t4

nephritis (> 50%) • Wire loop lesions

chi

• V : Membranous lupus (Nephrotic syndrome)

ra
al

• Pleuritis ± U/L exudative effusion (M/c) :

aw

Pleural fluid
r
ag

- Low glucose : < 30 g/L

|
w

- ↑LDH
ro

• Usually spared (No ILD)

• Caplan’s syndrome :
ar

• Pleuritis ± B/L exudative effusion (M/c)

M

Lung - RA + pneumoconiosis
• DAH with ↑activity
©

- ↑RF titers
• Shrinking lung syndrome
- Cavitatory nodules
• ILD : UIP (Most specific)
- Honeycombing
- No response to Rx
• Pericarditis without tamponade (M/c)
• Valvular heart disease : MR
• Accelerated atherosclerosis
CVS • Antiphospholipid antibody (APLA) syndrome
1/3 cases
Thrombosis (Coronary Artery)
• Libman-Sacks endocarditis

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 Rheumatology : RA and SLE 265

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

Nodular scleritis Large granular lymphocyte Episcleritis

CT scan : Honeycombing, Diffuse alveolar Muscular vasculitis :

Cystic changes in UIP hemorrhage (DAH) Infarcts and ulcers

om
l.c
ai
gm
Management 00:33:25
@
56

RA :
t4
chi

• Early intervention (6 wks - 1 yr) : Good outcome.

ra
al

• Very early RA (< 3 months) : Ideal stage for Rx.

r aw

• If > 2 years : Chronic stabilised RA (Bad prognosis).

ag
|
w

First line : Methotrexate.

ro
ar
M

Add on drugs : Other drugs :

©

• Sulfasalazine + HCQ. • Azathioprine.

• TNF inhibitors : • Cyclophosphamide.
- Adalimumab. • Calcineurin inhibitors.
- Golimumab.
- Certolizumab.
- Etanercept.
- Infliximab.
• JAK inhibitors : Tofacitinib.

SLE :
• Steroids Severe ± Cyclophosphamide/MMF.
• Rituximab : Resistant lupus.
• Low dose steroid + MMF : Maintenance.

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 266 Medicine

----- Active space ----- IF Patterns in Autoimmune Diseases 00:34:27

Homogenous : Nucleolar : Centromere :

• ds DNA Ab : SLE. Anti PM-Scl 70 : CREST syndrome.
(Disease activity) Polymyositis
• Antihistone Ab : DILE. scleroderma overlap.

om
l.c
ai
gm
@
56
t4

Speckled : Cytoplasmic :
chi

• Dense fine speckled (DFS-70) : • Anti-synthetase Ab.

ra
al

Rules out CTD. • Anti-Ro 52.

aw

• Fine speckled :
r
ag

- Anti-Ro 60.
|

- Anti-Mi2 antibody : Polymyositis.

w
ro

• Coarse speckled :
ar

- Anti U1RNP : MCTD.

M

- Anti-Smith antibody : SLE.

©

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 Systemic Sclerosis and Inflammatory Muscle Disease 267

SYSTEMIC SCLEROSIS AND INFLAMMATORY ----- Active space -----

MUSCLE DISEASE

• Systemic features + scleroderma (Thickening & hardening) = Systemic Sclerosis

(SSc).
• F>M

Differentials :
1. Scleredema A/w Diabetes.
2. Scleromyxedema A/w myeloma & paraneoplastic syndrome.
3. Nephrogenic systemic fibrosis Contrast induced (Gadolinium).
4. Eosinophilic fasciitis A/w aplastic anemia.

om
l.c
Scleroderma-like Lesions :

ai
gm
@
56
t4

Chemicals : Drugs : Dietary supplement :

hi

• Silica • Bleomycin
c

L-tryptophan
ra
al

• Vinyl chloride. • Pentazocine. (Contamination).

r aw
ag
|

Pathogenesis :
w
ro

•
ar

Systemic vascular injury

M
©

Vasculopathy & fibrosis + inflammation (least)

Capillary hypoxia.
• Endothelial mesenchymal differentiation.

Types of SSc 00:00:50

Based on Extent of Skin Involvement :

Limited SSc Diffuse SSc Sine scleroderma :

• No skin involvement.
• Raynaud’s phenomenon
(RP) + ulcers + PAH.

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 268 Medicine

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

Limited SSc Diffuse SSc

• 2˚ RP (long standing) :
- Puffy fingers
- Distal & digital ulcers
• Fatigue
- A/w critical limb ischemia
• RP : short, ↓severe
Clinical
• Tendon friction rubs
features Severe
• Arthralgia, myalgia
• A/w CREST syndrome :
• Scleroderma renal crisis (early onset)
- Calcinosis cutis
- RP - Sclerodactyly
- Esophagitis - Telangiectasia

• Diffused
• Skin changes :

om
Loss of body hair & oil

l.c
+

ai
Dry pruritic skin

gm
Skin involved Distal to elbow & face
@
56
Salt & pepper appearance :
t4

Hypo & hyperpigmentation

chi
ra
al

Thickening & tightening

r aw
ag

• Interstitial lung disease : NSIP (Restrictive

|

pattern + ↓DLCO)
w

- IOC : HRCT
ro

Pulmonary Artery Hypertension (PAH) class I :

ar

Complications • Cardiac anomalies :

M

15-20%
Restrictive cardiomyopathy
©

• Renal anomalies :
Thrombotic microangiopathy
• Anti-Topoisomerase I Ab (Anti-Scl-70)
• Anti-RNA polymerase III :
- Severe & rapidly progressive skin lesions
Antibody Anti-centromere Ab
- Malignancy
- GAVE (Gastric Antral Vascular Ectasia)
- Renal abnormality (most specific)

Images

Facial telangiectasia
Salt & pepper appearance

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 Systemic Sclerosis and Inflammatory Muscle Disease 269

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

Critical limb ischemia

HRCT : NSIP (GG0)

Images

om
CXR : B/L bibasal
reticular nodular infiltrates

l.c
Calcinosis

ai
gm
Note : @
56

Usual interstitial pneumonia (UIP) :

t4
hi

• A/w Rheumatoid arthritis.

c
ra
al

• CT findings :
aw

- Loss of lung architecture.

r
ag

- Honeycomb pattern.
|
w

- Septal thickening.
ro
ar

CT : UIP
- Traction bronchiectasis.
M
©

Raynaud’s Phenomenon 00:06:27

Cold Functional/reversible vasospasm.

Types :
1° RP 2° RP
• AKA Raynaud’s disease • A/w connective tissue disease (CTD) : SSc, mixed CTD
Features
• Benign • Pallor Cyanosis Redness
Age < 20 yrs 30-60 yrs
Pain - +
Critical limb aischemia - +
ANA - +
Symptoms Symmetrical, mild Severe
Dilatation : Early disease
Nail fold capillaroscopy No change Dropout : Active disease
Tortuosity : Chronic disease (DDT)
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 270 Medicine

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

SSc : Nailfold capillaroscopy findings Digital pitting

Rx :
1. Calcium channel blockers (CCB) : 1st line.
2. Phosphodiesterase - (PDE - ).

om
3. Losartan.

l.c
4. Prazosin.

ai
gm
5. Topical nitrates.
@
56

Treatment
t4

00:25:15
chi
ra

• Symptomatic treatment.
al
aw

• Steroids not used :

r
ag

- ↑Renal complication.
|

- ↓Useful.
w
ro
ar

Complication Rx
M
©

1. Ambrisentan
(Endothelin antagonist)
PAH
+
2. Tadalafil (PDE-5 - )
Renal anomalies ACE - (DOC)
RP CCB
ILD MMF

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 Systemic Sclerosis and Inflammatory Muscle Disease 271

Inflammatory Muscle Disease 00:26:26 ----- Active space -----

AKA idiopathic inflammatory myopathies.

Features :
• Systemic autoimmune disorders.
• Vasculopathy Endothelial injury & thrombus formation.
• Muscle infiltration (Mononuclear cells).
• Muscle weakness :
- Sub-acute to chronic.
- B/L symmetrical.
- Proximal muscle involvement (LL >> UL).
• No sensory involvement.
• Normal reflexes.

om
Types :

l.c
ai
gm
Features @ Antibody involved
56

• Anti Jo-1
t4
hi

• Anti-Mi-2 (Anti-helicase) :
c

Dermatomyositis (DM) Skin + muscle involvement

ra

- Max skin & muscle involvement

al
aw

- No ILD/malignancy risk
r
ag

Polymyositis (PM) Only muscle involvement Anti Jo-1

|
w

• Necrosis + • Anti-HmG-CoA reductase

ro

Immune-mediated
• A/w statin use (50%) Need (A/w statins use)
ar

necrotising myopathy
M

intense immunosuppression • Anti-SRP (Signal regulation peptide)

©

• Elderly age (M > F)

• Asymmetrical involvement :
Inclusion body myositis (IBM) Quadriceps Recurrent falls Anti-cytosolic 5’-nucleotidase-1a
• Distal muscle involvement
(Flexor digitorum profundus)
• Poor prognosis
• Anti-MDA-5 (Melanoma
Amyopathic • Rapidly progressive skin lesions +
differentiating antigen)
dermatomyositis interstitial lung disease (ILD)
• Anti-SAE
• Muscle manifestations -
• Vasculopathy + calcinosis cutis
Juvenile dermatomyositis • Anti-NxP2
• No risk for ILD & malignancy
• Anti-TIF1-γ
Cancer induced myositis DM > PM > IBM

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 272 Medicine

----- Active space ----- Dermatomyositis & Polymyositis 00:32:24

Dermatomyositis Polymyositis
• Children (5 - 15 years)
• Adults (50 - 60 years)
Incidence • Adults (40 - 60 years)
• F>M
• F>M
Association with
+ / - (Overlap/isolated) +
other diseases
+ (High) :
Association with • Ca lung (M/c)
+ (Minimal)
malignancy • Ca ovary (Specific)
• Nasopharyngeal carcinoma
• Endomysium & perimysium inflammation

om
• Necrosis -

l.c
ai
Histopathology • Perifascicular atrophy

gm
• Vascular involvement @ CD-8 + T-cell
56
• CD-4 + T-cell & B-cells
t4
hi

B/L symmetrical proximal muscle Pharyngeal muscles,

c
ra

weakness (Pain - )
al

neck flexors
aw

Progression
r
ag

Respiratory muscles (Late)

|
w

• Extra-ocular & facial muscles not involved

ro
ar

Anti-synthetase Syndrome :
M
©

Anti Jo-1 antibody (Anti-synthetase antibody).

Presentation : Acute.
• ILD :
- Non-specific interstitial pneumonia (NSIP) (M/c).
- Cryptogenic organising pneumonia (COP).
• Arthritis (SLE-like).
• Fever.
• Raynaud’s phenomenon.
• Mechanic’s hand :
Crusting & erosion of lateral aspect of index +
middle finger. Mechanic’s hand
• Cardiomyopathy.

Investigations :
Muscle biopsy : Gold standard.
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 Systemic Sclerosis and Inflammatory Muscle Disease 273

Skin Manifestations in Dermatomyositis 00:43:24 ----- Active space -----

Pathognomonic Signs :
1. Gottron’s papules :
• Dorsal aspect of MCP/PIP/DIP.
• Pruritus & MCP involvement + ( - in SLE).
• Midfacial rash : Nasolabial fold involved (Spared in SLE).

Flat-topped, scaly,
erythematous violaceous
papules/plaque

om
2. Heliotrope rash :

l.c
ai
gm
Violaceous periorbital
@
edema/erythema
56
t4
chi

Other Signs :
ra
al
aw

3. Gottron’s rash/Gottron’s sign : Macular erythema of MCP/DIP/PIP.

r
ag

(Involvement of entire hand Linear erythema).

|
w

4. V-sign : 8. Holster’s sign :

ro
ar
M
©

Anterior chest lesion

5. Scalp involvement : Pruritic. Rash on lateral aspect of thigh
6. Calcinosis cutis.
7. Shawl sign : 9. Nail signs :

Periungual erythema +
Nail fold telangiectasia

Posterior chest lesion

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 274 Medicine

----- Active space ----- VASCULITIS

Inflammatory destruction of vessel wall.

Classification of Vasculitis 00:00:58

Primary :
Predominant involvement Disease
• Giant cell arteritis (GCA)
Large vessel
• Takayasu arteritis
• Kawasaki disease
Medium vessel
• Polyarteritis nodosa (PAN)

om
Immune complex mediated : Anti neutrophil cytoplasmic antibody

l.c
• IgA vasculitis (ANCA) mediated :

ai
gm
(Henoch-Schönlein purpura) • Granulomatosis with polyangiitis (GPA)
Small vessel • Cryoglobulinemic vasculitis @ • Microscopic polyangiitis (MPA)
56

• Goodpasture syndrome • Eosinophilic granulomatosis with

t4
hi

• Hypocomplementemic urticarial polyangiitis (EGPA)/allergic

c
ra

vasculitis (Anti C1q antibody) granulomatosis with polyangiitis

al
aw

• Cogan’s syndrome
Variable vessel
r

• Behcet’s disease
ag
|

• Cutaneous leukocytoclastic angiitis

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• Primary CNS vasculitis

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Single organ
ar

• Isolated aortitis
M
©

Secondary :
Etiology Disease
Immune complex mediated : ANCA mediated :
Drugs • Penicillin • Hydralazine Small vessel
• Sulfonamides • Propylthiouracil (PTU) vasculitis
• Hepatitis B virus associated PAN (Medium vessel)
• Hepatitis C virus associated cryoglobulinemic vasculitis (Small vessel)
Infections
• TB Large vessel vasculitis
• Syphilis
Malignancy
• Hairy cell leukemia associated PAN (Medium vessel)
(Immune complex mediated
• Paraneoplastic syndromes (Small vessel)
small vessel vasculitis)
• Ankylosing spondylitis Aortitis Large vessel
• IgG4 related disease Aortitis + paravertebral mass
Connective tissue diseases
• SLE CNS vasculitis & mesenteric vasculitis Small
• RA Muscular artery (Reticular dermis) Ulcers & gangrene vessel

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 Vasculitis 275

Large Vessel Vasculitis 00:09:45 ----- Active space -----

Giant Cell Arteritis (GCA) vs. Takayasu Arteritis :

GCA Takayasu arteritis

• < 40 years (Median : 24 years)
• > 50 years (Median : 72 years)
Incidence • F:M=9:1
• F:M=3:1
• Asians (M/c)
• Fragmentation of internal elastic lamina (Cranial vessels spared)
Histopathology
• Transmural inflammation + mononuclear cells + giant cells (Few) ± granulomas
Superficial temporal (M/c) > vertebral >
ophthalmic > posterior ciliary artery (A/w
Arteries affected Lt. subclavian artery (M/c)
anterior ischemic optic neuropathy & causes
altitudinal hemianopia)
• Typical GCA :
• Carotidynia (Tenderness over

om
- U/L or B/L temporary/permanent
carotid arteries)

l.c
visual loss (Most dangerous)
• Upper limb claudication

ai
- New-onset localized headache with

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• Asymmetry in pulse & BP
periodicity + ↑ESR (> 50 mm/hr) @
Clinical features • Subclavian/carotid/aortic bruit
56
- Jaw claudication (Specific symptom)
• Renal artery stenosis (RAS)
t4

- Tenderness of artery with ↓pulsations/

hi

& renovascular hypertension

c

prominent vessel with nodules

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(RVH)
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• Atypical GCA :
• Pulmonary artery involvement
aw

- Pyrexia of unknown origin (PUO)

r
ag

• 30%
Involvement of aorta 100%
|

• A/w thoracic aorta aneurysms

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ro

Association with PMR + (> 50%) GCA + PMR syndrome -

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M

• Colour Doppler USG Halo sign

©

• CT angiogram (IOC)
Investigations • IOC : Temporal artery biopsy (Skip lesions + )
• MR angiogram
• PET scan : To rule out aortitis
• Steroids (Started immediately on suspicion) • Steroids
Treatment
• Tocilizumab (IL-6 inhibitor) • Surgical intervention : RAS & RVH

Halo sign :
Hypoechoic area
around temporal
artery trunk
Longitudinal view Transverse view

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 276 Medicine

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

Note :
• Vasculitic disorders that form granulomas :
a. GCA. e. Primary CNS vasculitis.
b. Takayasu’s arteritis. f. Cogan’s syndrome.
c. GPA. g. Rheumatoid vasculitis.
d. EGPA.
• Polymyalgia rheumatica (PMR) :
- Clinical features :
Pain + stiffness of hip, shoulder & pelvic girdle (Myositis/tendinitis).
• Lasts for 30 mins.
• Improves with activity.
• ↑ESR (> 50 mm/hr).
• Rx : Low-dose steroids.

om
l.c
ANCA Mediated Small Vessel Vasculitis

ai
00:22:47

gm
• ANCA A ntibodies against proteinase-3 & myeloperoxidase (MPO) in
@
56
neutrophilic granules.
t4
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• Screening test : Indirect immunofluorescence (IIF).

c
ra

• Confirmatory test : ELISA.

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aw

• ANCA titres do not correlate with disease activity.

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ag

True c-ANCA +ve True p-ANCA +ve False p-ANCA +ve

|
w
ro
ar
M
©

IIF patterns

Cytoplasmic Perinuclear
Ab against
proteinase-3 + (Titre ≥ 1 : 10) - -
ELISA
Ab against MPO - + -
• Renal limited vasculitis (70%) : M/c
• MPA (50%)
• Autoimmune hepatitis
• EGPA (40%)
• Primary sclerosing
• GPA (75%) : M/c • GPA (20%)
cholangitis
• MPA (40%) • Drugs :
• Rheumatoid arthritis
Causes • Renal limited - Hydralazine
• IBD
vasculitis (20%) - PTU
• Infective endocarditis
• EGPA (5%) - Minocycline
(IE)
- Cocaine adulterated
• Cystic fibrosis
- Levamisole
• Goodpasture syndrome
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 Vasculitis 277

Histopathology : ----- Active space -----

1. Necrotizing vasculitis.
2. Fibrinoid necrosis.
3. Granulomas + / - .
4. Pauci immune (IIF).

Glomerular Vessel wall

inflammation inflammation

om
l.c
ai
gm
@ Fibrinoid necrosis
56
t4
chi
ra
al
aw

Histopathology in ANCA +ve small vessel vasculitis

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ag
|
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ar
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©

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 278 Medicine

----- Active space ----- GPA vs. MPA vs. EGPA vs. PAN 00:35:37

EGPA (Churg
GPA (Wegener’s granulomatosis) MPA PAN
Strauss syndrome)
Age group 40 - 60 years Elderly 40 - 60 years -
+ve (40 - 45%)
ANCA c-ANCA > p-ANCA p-ANCA > c-ANCA -ve
-ve (> 50%)
Granuloma + - + (Extravascular) -
Medium vessels
Vessels Small vessels +
Small vessels (Mesenteric, renal &
affected medium vessels
testicular artery)
Constitutional
symptoms
+ ++ - +++
• Serous otitis media

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• Midline nasal deformities
Asthmatic phase

l.c
• Recurrent sinusitis
Upper airway (Obstructive

ai
(S. aureus) 95% Sinusitis (30%)

gm
disease airway disease +
• Recurrent epistaxis @ nasal polyps) Spared
56
• SNHL
t4

• Subglottic stenosis
chi

• Cavitary nodules
ra

Lungs
al

• Diffuse alveolar 90% DAH (50%) + in ANCA +ve

aw

hemorrhage (DAH)
r
ag

Renal artery
|

stenosis/aneurysm
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Rapidly progressive
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Renal RPGN type 3

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glomerulonephritis (60%) Mild

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(100%) RVH
(RPGN) type 3
©

Renal failure
• Nodular scleritis (Characteristic)
Ocular • Episcleritis (M/c) -
• Orbital pseudotumour
• Deep ulcers
• Nodules
Skin + +++ Ulcers
• Gangrene
• Livedo reticularis
Peripheral ++ +++ ++
nervous system + (Mononeuritis (Mononeuritis
(Peripheral neuropathy)
multiplex) multiplex)
• Steroids + cyclophosphamide/rituximab Mepolizumab
Treatment -
• Azathioprine + low-dose steroids (Maintenance) (IL-5 inhibitor)

Major manifestations
Minor manifestations

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 Vasculitis 279

Other Features : ----- Active space -----

GPA : Strawberry gingivitis, oral ulcers.

EGPA :
• Asthmatic phase Eosinophilic phase (Fleeting infiltrates with eosinophilia)

Vasculitic phase.
• ANCA +ve ↑Risk of DAH, RPGN (Bad prognosis).
• Medium vessel involvement + Mononeuritis multiplex and ulcers.
• Complications :
- Eosinophilic gastroenteritis.
- Eosinophilic myocarditis (M/c cause of death).

PAN :

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l.c
• A/w ADA-2 deficiency (Children).

ai
gm
• Histopathology :
@
Necrotising transmural vasculitis (Focal & segmental) with fibrinoid necrosis.
56
t4

• 30 : 1 rule :
chi

- 30% PAN patients have HBV.

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al

- 1% HBV patients have PAN.

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ag
|

Immune Complex Mediated Small Vessel Vasculitis 00:54:26

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ro
ar

• Immune complex + .
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• ANCA -ve.
Histopathology :
• Neutrophilic inflammation.
• Leukocytoclastic vasculitis :
Leukocytoclasis + (Fragmented neutrophils/neutrophilic debris).

Clinical Features :
• Cutaneous palpable purpura (M/c) :
- In crops.
- Non-thrombocytopenic.
- Non-blanching.
- Symmetrical.
- Lower limbs (Extensor surface).
• Vesicle, bulla, urticaria, superficial lesions.
Palpable purpura
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 280 Medicine

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

IgA Vasculitis vs. Cryoglobulinemic Vasculitis :
IgA vasculitis Cryoglobulinemic vasculitis
• Children (M/c) : < 5 yrs, B > G
Incidence Self-limiting disease (Good prognosis) Middle age to elderly
• Adults : RPGN (Bad prognosis)
Vessels affected Small vessels Small + medium vessels
• Palpable purpura
Skin Palpable purpura • Ulcers (D/t muscular artery
involvement)
Arthritis (Mnemonic : KLMNO) :
• Knee joint
• Large joint
Joints SLE like arthritis
• Migratory
• Non-deforming
• Oligoarthritis

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• Colicky pain (Bowel angina)

l.c
• Intussusception

ai
GIT A/w HCV (Good prognosis)

gm
@
Ileoileal (Most dangerous complication)
56
t4

IgA nephropathy :
Membranoproliferative
hi

Renal • Asymptomatic microhematuria

c
ra

glomerulonephritis (MPGN)
• Proteinuria (Mild)
al
aw

Other • Testicular involvement

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Mononeuritis multiplex
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manifestations • Scrotal swelling

|

Investigations Renal biopsy : IgA deposition ↓Complement (C4 )

w
ro

• Self-limiting disease
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M

Treatment • Steroids HCV management

©

(In severe joint/GIT involvement)

Other Features :
Cryoglobulinemic vasculitis :
• Types :
- Type 1 : Monoclonal IgM a/w Waldenstrom macroglobulinemia.
- Type 2 : Monoclonal IgM + polyclonal IgG Mixed (Seen in HCV &
- Type 3 : Polyclonal Sjogren’s syndrome).
• Meltzer’s triad :
Fatigue

Palpable purpura Arthralgia

• Cryoprecipitate + (Cryoglobulin : Immunoglobulin that precipitates in cold).

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 Spondyloarthropathies 281

SPONDYLOARTHROPATHIES ----- Active space -----

Spondyloarthritis (SpA) :

Features :
• Asymmetric, lower limb involvement • M/c extra-articular manifestation :
(M/c). 4 A uveitis.
• HLA-B27 : +ve. - Asymmetrical.
• Rheumatoid factor - Anterior.
• Subcutaneous nodules - - Acute.
• Extra-articular features of RA - Alternating.

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l.c
Types :

ai
gm
@
56
Axial predominant Peripheral predominant
t4
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Non-radiographic Ankylosing Reactive Psoriatic arthritis IBD related arthritis

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axial SpA. spondylitis. arthritis.

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No axial involvement.
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ag
|
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Axial Predominant SpA 00:00:33

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©

Features of inflammatory back pain :

• Age < 45 years. • Morning stiffness : Lasts > 30 mins.
• Duration > 3 months. • Worsens with rest & causes night
• Insidious onset. awakenings.
• Deep seated lower lumbar • Improves with activity & NSAID use.
/gluteal pain. • ↑ESR.

Non-radiographic axial SpA :

• Clinical features suggestive of SpA ±
5 - 10 yrs X-ray features Ankylosing
MRl features
• No X-ray features suggestive of sacroilitis s/o sacroilitis (5 - 10%) spondylitis.
• Incidence :
- M>F
- HLA B27 +Ve

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 282 Medicine

----- Active space ----- Ankylosing Spondylitis :

Features :
• Inflammatory granulation tissue Erosion + calcification of annulus fibrosis

↑Spine fractures B amboo Fusion of Syndesmophyte formation

spine vertebra (Thin, marginal, symmetrical)
• Root joint (Shoulder & hip) involvement.
• Peripheral joint involvement - .
• Dactylitis - .
• Enthesitis :
- Achilles tendinitis.
- Costochondritis.
- Plantar fasciitis.

om
l.c
• Extra-articular manifestations :

ai
gm
- Lung involvement : Upper lobe ILD.
- Cardiac : Aortic regurgitation. @
56
t4

Investigations :
chi

X-ray findings :
ra
al
aw

• Bony erosions Romanus sign. X-ray : Bamboo spine

r
ag
|

• Ossification Shiny corner sign.

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Loss of sacroiliac joint space

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ar

+ sclerosis
Treatment : NSAIDs.
M
©

Normal vs. AS Romanus sign

Peripheral Predominant SpA 00:04:23

Reactive Arthritis :
Causes :
Post-infective :
Infection Organism M : F ratio
Genitourinary tract (Urethritis) Chlamydia trachomatis (M/c worldwide) 9:1
Gastrointestinal tract Shigella flexneri (M/c in India) 1:1

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 Spondyloarthropathies 283

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

• AAP arthritis : • Dactylitis.
- Asymmetrical. • Axial involvement (30%) :
- Additive. - Asymmetrical.
- Painful. - Paravertebral ossification
- Non-purulent. Syndesmophytes (Coarse, fluffy,
• Enthesitis. marginal).
• Mucocutaneous features :
- keratoderma blennorrhagicum Hyperkeratotic vesicleson palms & soles
with crusting.
- Circinate balanitis Painless, shallow, ulcer on glans penis.
Treatment : NSAIDs.

om
l.c
ai
gm
@
56
t4
chi
ra
al
aw

Keratoderma blennorrhagicum Circinate balanitis Dactylitis

r
ag
|
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ro

IBD Arthritis :
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M

Types :
©

Type 1/LMAP Type 2/SMAP-U

• Small joints involvement
• Large joints involvement (M/c : knee)
• Migratory
• Migratory
• Aggressive
Features • Asymmetrical
• Polyarticular arthritis
• Pauciarticular arthritis
• Uveitis
• A/w activity
• Unrelated with activity
Prognosis Self-limiting Poor

Psoriatic Arthritis :
• Psoriatic patients 5 - 30% Psoriatic arthritis.
• 60/20/20 rule :
- 60% : Psoriasis f/b arthritis.
- 20% : Psoriasis & arthritis simultaneously. Pustular psoriasis :
- 20% : Arthritis f/b psoriasis. • Most destructive arthritis
• A/w HIV
• HLA CW-06 : +ve.
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 284 Medicine

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

Features :
• Arthritis :
- Erosive, small joint involvement (MCP, PIP, DIP) Ray pattern.
OR
- Asymmetrical , large joint involvement.
• Skin manifestations.
• Nail manifestations (90 - 95%).
• Dactylitis.
• Enthesitis.
• Posterior uveitis.

Treatment :
• Anti TNF-α (DOC).
• Methotrexate.

om
l.c
• IL-17 inhibitor : Secukinumab.

ai
gm
Nail manifestations
Pencil in cup deformity 56
@
t4
chi
ra
al
raw
ag
|
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ro
ar
M
©

X-ray : Arthritis mutilans

Note
Rheumatoid
Chronic gouty arthritis Psoriatic arthritis Osteoarthritis
arthritis
Arthritis mutilans : • Juxtaarticular
• Asymmetrical
• Marginal erosions osteopenia
• Punched out lytic lesions • Loss of joint space
• Small joint ankylosis • X-ray :
• Overhanging edges/ • Osteophytes +
• Telescoping of digits - Row pattern joint
Martel’s G sign • Subchondral sclerosis
• Periostitis involvement
• Sclerotic borders
• New bone formation + - DIP spared

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 Spondyloarthropathies 285

Crystal Arthropathies 00:15:21 ----- Active space -----

Acute Gout :
Etiology :
Monosodium urate monohydrate crystals (MSUM) : Red swollen joint
• Strong negative birefringence. with periarticular
• Needle-shaped crystals. erythema
Features : Acute onset pain (4 - 12 hrs).
Acute gout
Imaging :
Tophi Progresses to
Soft tissue shadow
Femoral Hyaline cartilage
cortex (Hypoechoic) Uric acid crystal

om
l.c
Chronic tophaceous gout

ai
gm
@
56
t4
chi
ra

X-ray USG : Double contour sign

al
aw

Treatment :
r
ag

• NSAIDs
|
w

• Steroids Acute attack.

ro
ar

• Colchicine
M
©

• Febuxostat
↓Uric acid (Prophylaxis after acute attack).
• Allopurinol
CPPD Disease :
Patterns :
• Pseudogout.
• Pseudo RA.
• Pseudo OA Hook-like osteophyte.
Etiology :
Calcium pyrophosphate dihydrate crystals :
Weak +ve birefringence.
Associations :
• Hypomagnesemia
Pseudogout.
• Gitelman’s syndrome
Chondrocalcinosis : Pseudogout pattern
• Hemochromatosis Pseudo OA.
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