GASTROENTEROLOGY

Q. ACUTE PANCREATITIS
Etiology
 I – Infections (CMV, Mumps, Echovirus, Ascaris, Clonorchis)
 G - Gallstones
 E - Ethanol
 T - Trauma
 A – Autoimmune (SLE, PAN)
 S – Scorpion sting
 H – Hyperlipidemia, Hypercalcemia
 E - ERCP
 D – Drugs (Steroids, Valproate, Azathioprine, Thiazide diuretics)
Pathogenesis
Pancreatic injury

Release of inflammatory mediators [TNF-alpha, IL-1]

Premature activation of Zymogen granules

Trypsinogen activated by Enterokinase into Trypsin  Activation of Protease, Phospholipase, Elastase

Digestion of Pancreatic & Surrounding tissue  SIRS & MODS

Symptoms
 Nausea
 Vomiting
 Hiccough
 Retching
 Oliguria
 Mohammed Prayer sign - sudden abdominal pain, with partial relief on leaning forward
Signs
 Tachypnea
 Hypotension
 Tachycardia
 Facial flushing
 Turner's sign – hemorrhagic pigmentation around flanks
 Cullen’s sign – pigmention around umbilicus
 Fox sign – inguinal ecchymosis
Complications
 Pancreatic necrosis
 Fat necrosis
 Acute tubular necrosis
 Disseminated intravascular coagulation
 Respiratory failure - ARDS
 Hematemesis/Malaena due to duodenal necrosis
 Splenic vein thrombosis
Differential diagnosis
 Perforated duodenal ulcer
 Ectopic pregnancy
 Diabetic ketoacidosis
 Intestinal obstruction
Investigations
 PANCREATIC FUNCTION TESTS
o Serum Amylase
o Serum Calcium
o Serum Lipase
o Serum Lactesence [due to elevated Triglyceride]
o Serum Trypsin
o Amylase : Creatinine clearance ratio
o Trypsinogen activation polypeptide (TAP) assay
o Phospholipase A2
o Blood glucose → Hyperglycemia
o LDH levels
 US abdomen
 Spiral CT
 CXR → Pleural effusion, ARDS
 Abdominal plain X-ray
o Colon cut off sign → Transverse Colon distension, Descending Colon collapse
o Renal halo
o Obliteration of Psoas shadow
o Localized Ground glass appearance
Management
 Admission into ICU
 Analgesics – Metamizole, Buprenorphine
 Antibiotics – in case of cholangitis
 Enteral feeding for nutrition
 Fluid therapy – Ringer lactate
 Supplement Oxygen
 Monitoring of Urine output and Blood gas analysis
 Monitoring –
o LFT
o RFT
o Coagulation profile
o Serum calcium
o Blood glucose
 Gall stone Pancreatitis – ERCP within 72 hours with CBD stenting
 Laparotomy → Necrosectomy
 Continuous closed peritoneal lavage
Prognosis of Acute pancreatitis
 RANSON CRITERIA [Score > 3  indicates Severe AP & Increased Mortality]
o On admission →
 Age > 70 years
 Blood sugar > 220 mg%
 LDH > 400 IU/L
 AST > 250 IU/L
o Within 48 hours →
 Hematocrit drop > 10%
 BUN rise > 2 mg%
 Serum Calcium < 8mg%
 Fluid sequestration > 4L

SEVERE ACUTE PANCREATITIS

Risk factors
 > 70 years
 BMI > 30
Associated with
 Shock
 Respiratory failure (PaO2 < 60 mm of Hg)
 Renal failure (serum creatinine > 2 mg)
 GI bleed
 Multi-organ failure
 RANSON score > 3
 Apache II score > 8
Q. CHRONIC PANCREATITIS
Etiology
 Alcohol
 Tropical pancreatitis
 Obstructive pancreatitis
 Autoimmune pancreatitis
 Hyperlipidemia
 Hyperparathyroidism
 Trauma
 Cystic fibrosis
Pathogenesis
 Oxidative stress hypothesis
o Chronic reflux of bile → Pancreas damage
 Toxic metabolite theory
o Alcohol directly damages Pancreatic acinar cells
 Stone & duct obstruction theory
o Alcohol increases Lithogenicity of Pancreatic juice → Stone Formation & Duct Obstruction

Clinical features
 Abdominal pain
 Diarrhoea / Steatorrhea
 Malabsorption
 Endocrine disruption
o Brittle diabetes
o Insulin deficiency → Diabetes mellitus
o Glucagon deficiency
 Exocrine disruption
 Mass per abdomen → tender, just above umbilicus
 Mallet-Guys sign → Right knee-chest position → Tenderness on Palpation of Left Hypochondrium
 Classical triad of chronic pancreatitis
 Pancreatic calcification
 Steatorrhea
 Diabetes mellitus

Complications
 Pancreatic pseudocyst
 Pancreatic ascites
 Pancreatic fistula
 Carcinoma pancreas
 Portal vein thrombosis
 Left side pleural effusion

Differential diagnosis
 Carcinoma of head of pancreas
 Retroperitoneal tumor
Investigations
 Blood glucose
 LFT
 Stool examination
o Fecal elastase < 200 ug /g
o Steatorrhea > 7 grams/ day
 Secretin cholecystokinin test – assess pancreatic function
 ERCP – Chain of Lake appearance
 CT abdomen – Pseudocyst, Calcification, Duct Stones
 EUS (Endosonography) → Malignancy, Duct Status, CBD status
Treatment
 Conservative
o Avoid alcohol
o Low fat diet
o Analgesics
o Pancreatic enzyme replacement therapy
o Control of diabetes using insulin
 Surgery
o Drainage procedure
 Puestow procedure
 Whipples procedure
 Bergers procedure
 Frey's procedure
 Bern’s procedure
 Resection + drainage procedure
 Duodenum preserving, Pancreatic head resection (DPPHR)
o Total Pancreatectomy
Q. DYSPEPSIA
Dyspepsia is collective syndrome of variety of gastrointestinal symptoms.
 Upper abdominal pain
 Early Repletion or Satiety after meals
 Gastro-esophageal reflux & heartburn
 Anorexia, Nausea & Vomiting
 Abdominal distension or Bloating
 Flatulence (burping, belching) & Aerography
Causes
 Functional dyspepsia
 Dyspepsia associated with Organic Diseases of Upper Gastrointestinal Tract
o Peptic ulcer
o Peptic Esophagitis
o Gastroesophageal reflux disease (GERD)
o Gastric carcinoma
o Lactose intolerance
 Dyspepsia associated with other conditions
o Pancreatic diseases
o Crohn's disease
o Colon malignancy
o Cardiac, Renal, Hepatic failure
o Carcinoma lung
 Drugs
o Acarbose
o Metformin
o Miglitol
o Bisphosphonates
o Non-steroidal anti-inflammatory drugs
o Corticosteroids
 Alcohol
 Pregnancy
 Depression
 Anxiety neurosis
Q. HAEMATEMESIS
Upper UGI bleeding indicates bleeding proximal to duoden-jejunal junction (ligament of Treitz).
Presents with Haematemesis, Melaena or both
Etiology
Oesophageal causes Gastroduodenal causes Miscellaneous causes
 Oesophageal varices  Erosive Gastritis  Rupture of Aortic Aneurysm
 Oesophagitis  Erosive Duodenitis  Coagulation defects
 Oesophageal carcinoma  Stress ulcers  Vascular malformations
 Mallory-Weiss syndrome  Peptic ulcer
 Gastric carcinoma
Clinical features
 Blood in Vomitus
o Bright Red blood → rapid hemorrhage
o Coffee ground color → small bleed
 Melaena [tarry black, foul smelling stool]
o 60 ml of blood is required to produce Melaena
o Blood must remain in GIT for 8-14 hrs to produce Melaena
 Pallor
 Shock
 Syncope
 Features Suggesting Severe Bleeding
o Presence of clots in vomitus
o Fresh blood in nasogastric aspirate
o Hematochezia
o Hypotension & Tachycardia
o Orthostasis
 Change of posture from Supine to Sitting position leads to
 Fall in systolic blood pressure >10 mmHg
 Rise in pulse rate of >20 beats/minute
Investigations
 Haemoglobin
 Haematocrit
 Blood urea : creatinine ratio > 72 → indicates Upper GI bleed
 Coagulation profile
 Liver function tests.
 ECG → rule out Acute Coronary Syndrome.
 Nasogastric aspirate.
 Upper GI endoscopy.
 Angiography
Management
 Gastric Lavage
 Proton-Pump Inhibitors
 Antifibrinolytic Drug → Tranexamic acid
 Balloon Tamponade, Vasopressin, Octreotide
 Endoscopic Therapeutic Electrocoagulation
Surgical Measures
 Shunt surgery / Transaction-devascularization of esophageal varices.
 Total gastrectomy
Q. ACUTE DIARRHOEA
Causes
Bacterial Viral Parasitic Drugs
Vibrio cholerae Rota virus Giardia lamblia Laxatives
ETEC Adenovirus Cryptosporidium Sorbitol
EIEC Norwalk agent Entamoeba histolytica Lactulose
Salmonella Astrovirus Quinidine
Shigella Coronavirus Diuretics
Campylobacter Digitalis
Yersinia enterocolitica Propranolol
Theophylline
Alcohol
Antibiotics

Q. CHRONIC DIARRHOEA
Causes
 Chronic Enteric Infection
o Salmonella
o TB
o Giardiasis
o Strongyloides
o Trichuriasis
o Cryptosporidium
o Microsporidium (common in patients with AIDS)
o Isospora
 Inflammatory bowel disease [Ulcerative colitis, Crohn's disease]
 Malabsorption Syndrome
 Endocrine
o Zollinger-Ellison syndrome
o Hyperthyroidism
o Carcinoid
o Non-β cell Pancreatic tumour
o Villous adenoma
 Motility disorder
o Irritable bowel syndrome
o Post-vagotomy syndrome
Q. MALABSORPTION SYNDROME
Malabsorption refers to defective mucosal absorption of essential nutrients, electrolytes, minerals & vitamins
Etiology
 Defects in
o Luminal phase
o Mucosal phase
o Transport phase
Luminal phase defects Mucosal Phase defects Transport Phase defects
Substrate Hydrolysis Defect Brush Border Hydrolysis Defect Lymphatic Obstruction
 Enzyme deficiency  Disaccharidase deficiency Lymphangiectasia
o Chronic pancreatitis
Epithelial Transport Defect Vascular Intestinal ischemia
o Pancreatic carcinoma
 Hartnup disease
 Enzyme inactivation
 Cystinuria
o ZE syndrome
 Rapid transit  Intestinal resection

o Post-gastric surgery  Coeliac disease

Fat Solubilization Defect  Tropical sprue
 Decreased bile salt synthesis  Crohn’s disease
o Parenchymal liver disease  Radiation
 Impaired biliary secretion
 Ischemia
o Cholestatic jaundice
 Whipple’s disease
 Increased bile salt loss
 AIDS
o Terminal ileal resection
Luminal Availability Defect Epithelial Processing Defect

 Lack of intrinsic factor  Abetalipoproteinemia

 Pernicious anemia
 Blind loop syndrome
 Bacterial overgrowth
Drugs Systemic Diseases
 Colchicine → Inhibits crypt cell division  Addison's disease
 Neomycin → Precipitation of bile salts  Thyrotoxicosis
 Methotrexate → Folic acid antagonist  Hypothyroidism
 Cholestyramine → Binding bile salts  Diabetes mellitus
 Laxatives → Multiple mechanisms  Collagen vascular diseases
Treatment
 Correction of nutritional deficiencies
o Gluten-free diet → in coeliac disease
o Pancreatic Enzyme replacement → in pancreatic insufficiency
o Low-fat diet & Cholestyramine → bile acid deficiency
o Replacement therapy
o Oral folic acid
o Oral iron
o IM B12
o Vitamin D & calcium
o Electrolyte correction
 Treatment of underlying disorder
Clinical features
 Insidious onset
 Gradual progression
 General features
o Diarrhoea
o Abdominal pain
o Abdominal Distension
o Loss of weight
o Anaemia
 Specific features → Due to defective absorption of different constituents
o Protein → Emaciation, Pitting pedal oedema
o Fat → Loss of weight, Steatorrhea
o Carbohydrate → Abdominal Distension, Belching, Bloating
o Vitamins
 Vitamin A → Night blindness, Xerophthalmia, Keratomalacia
 Vitamin D → Tetany, Osteomalacia
 Vitamin C → Scurvy
 Vitamin K → Haemorrhagic tendencies
 Vitamin B1 & B2 → Angular Stomatitis, Cheilosis, Glossitis
 Vitamin B3 → Pallegra → 5D’s → Dermatitis, Diarrhea, Dementia, Depression, Death
 Vitamin B12 & Folic acid → Macrocytic Anaemia, Glossitis, Neuropathy
Investigations
 Barium meal → Specific structural abnormalities
 Tests for fat absorption
o Sudan staining of stool for fat globules.
o Stool fat excretion in 1 day is > 7 g (normal is less than 7 g/day on a 100 g/day of fat diet).
o Measurement of fat-soluble vitamins (A, D, E, K) levels in the bloo
 Tests for carbohydrate absorption
o Glucose tolerance test
o Low blood sugar level
o D-xylose absorption test
o LTT (lactose tolerance test)
o Hydrogen breath test to diagnose lactase deficiency
 Tests for protein absorption
o Serum albumin level
 Test for bile acid malabsorption.
o Selenium Homocholic Acid Taurine (SeHCAT) test
 Wireless capsule endoscopy
 Small intestinal biopsy
Q. GASTRO-OESOPHAGEAL REFLUX DISEASE [GERD]
Pathological reflux from stomach into lower oesophagus
Etiology
Obesity
Reduced LES pressure
Anticholinergics
 CCB
 Diazepam
 Alcohol & Smoking
 Caffeine & Theophylline
Altered esophageal clearance mechanism
Delayed gastric emptying
 Gastroparesis
 Medication
 Diabetes
 Gastric distension
Gastric acid hypersecretion

Pathogenesis
Gastric fundus distention

Exposure of LES to Gastric acid

Esophagitis

Increased stimulus to Swallow saliva & Drink water to neutralize esophagitis

Further fundal distinction

Sphincter gets stretched into Gastric fundus

Erosion, Ulceration, Mucosal Metaplasia

Clinical features
 Classic triad
1. Heart burn (Pyrosis) → pain more in supine position
2. Regurgitation
3. Epigastric pain (radiating to back)
 Fatty dyspepsia
 Odynophagia (painful swallowing)
 Laryngeal symptoms → hoarseness of voice
 Hematemesis
 Recurrent pneumonia
 Water brash  Reflux of acid or bile into mouth in GERD leading to Excess Salivation
Complications
Esophageal Extra-esophageal
Esophagitis Laryngo-pharyngeal reflux
Stricture Nocturnal asthma
Barrett’s esophagus Recurrent pneumonia
Adenocarcinoma
Differential diagnosis
 Achalasia cardia
 Cardiac angina
 Peptic ulcer
 Gall stones
 Carcinoma esophagus
 Pancreatic diseases
Investigations
 Ambulatory 24-hour pH monitoring
 Esophageal manometry – identify associated motility disorders
 Impedance manometry – identify type and nature of reflux
 Barium swallow study
 Video Esophagography
 Endoscopy - for Strictures, Shortening, Hiatus Hernia
 Mucosal biopsy - confirm metaplastic transformation
Treatment
 Lifestyle changes
o Weight loss
o Avoid caffeine alcohol & smoking
o Small frequent meals
 Drugs
o H2 antagonist – cimetidine, ranitidine, famotidine
o PPI – rabeprazole, lansoprazole, pantoprazole
o Prokinetcs – metoclopramide, domperidone, cisapride, mosapride
 Endoluminal Therapy
o Endoluminal suturing
o Endoscopic full-thickness plication
o Enteryx injection technique – endoscopic injection of synthetic implant -> enhance LES strength
 Surgery
o FUNDOPLICATION -> fundus is wrapped around the esophagus and sutured
 Nissens posterior total fundoplication – 360 degree wrap
 Toupet posterior fundoplication – 270 degree wrap
 Dor anterior fundoplication – 180 degree wrap
 Watson Anterior fundoplication – 90 degree wrap
o COLLIS GASTROPLASTY
Q. ACID PEPTIC DISEASE / PEPTIC ULCER DISEASE / HELICOBACTER PYLORI
Peptic ulcer refers to an ulcer
 Lower esophagus
 Stomach
 Duodenum
 Jejunum after surgical anastomosis to stomach
 Ileum adjacent to Meckel's diverticulum.

Etiopathogenesis
 Direct Mucosal damage
o Gastric hyperacidity
 H. pylori infection
 Parietal cell hyperplasia
 Zollinger-Ellison syndrome
o NSAID
 Direct chemical irritation
 Suppresses prostaglandin synthesis
 Reduces bicarbonate secretion.
o Corticosteroids
o Duodenal Gastric Reflux
o Smoking & Alcohol
 Impaired Gastric Defense mechanism
o Ischemia
o Shock
o Delayed Gastric emptying
H. pylori induced Ulcer
 H. pylori converts Urea into Ammonia → Combination of Ammonia & Water → Formation of Free Radicals →
Disruption of Gastric epithelial integrity → Ulcer

Clinical Features
 Epigastric pain
o Pointing sign → sharply localized, the patient will localize site with one finger
o Burning in character
 Hunger pain
o Pain occurs on empty stomach (hunger pain) and is relieved by food or antacids.
 Night pain
o Pain wakes patient from sleep around 3 am & is relieved by food, milk, antacids, belching, vomiting
 Water brash  Reflux of acid or bile into mouth in GERD leading to Excess Salivation
 Heart burn
 Loss of appetite
 Anorexia
 Bloating
 Dyspepsia
Complications
 Perforation
 Bleeding
o Gastroduodenal artery → source of bleeding in duodenal ulcer
o Left gastric artery → source of bleeding in gastric ulcer.
 Gastric outlet obstruction
 Gastric malignancy
 Pancreatitis (due to posterior penetration of ulcer)
Investigations
 Double contrast Barium meal
 Endoscopy & Biopsy
o Benign gastric ulcer → MC in Lesser curvature at Incisura.
o Malignant gastric ulcer → MC in Greater curvature
 Serum gastrin → rule out Zollinger-Ellison syndrome
 Tests for H. pylori
o Invasive endoscopic biopsy
 Rapid urease test (false negative with recent use of PPI, antibiotics)
 Histology (sensitivity reduced with use of PPI, Antibiotics & Bismuth compounds)
 Culture
o Non-invasive
 Serology for immunoglobulin G
 Urea breath test (false negative with recent use of PPI, antibiotics)
 Stool antigen test (sensitivity reduced with use of PPI, Antibiotics & Bismuth compounds)
Management
 General Measures
o Avoid smoking & Alcohol
o Avoid aspirin and NSAIDs
 Antacids → 15-30 mL liquid antacid 1 and 3 hours after food & at bedtime for 4-6 weeks
o Side effects
 Aluminum compounds → Constipation, Phosphate Depletion
 Magnesium compounds → Diarrhea, Hypercalcemia & Hypermagnesemia
 Calcium → Milk-alkali Syndrome (Hypercalcemia, Alkalosis & Renal Impairment)
 Bicarbonate compounds → Alkalosis
 Sodium compounds → water retention → exacerbation of cardiac failure & ascites

 Treatment for H. pylori

o Triple therapy [BID]
 Omeprazole 20 mg
 Metronidazole 500 mg
 Clarithromycin 500 mg
o Quadruple therapy [QID]
 Omeprazole (20 mg)
 Metronidazole 500 mg
 Bismuth subsalicylate 500 mg
 Tetracycline 500 mg
Differences between Gastric & Duodenal ulcers
Features Gastric ulcer Duodenal ulcers
Common site Lesser curvature First part of duodenum
Incidence Less common More common
Association with H. pylori Less common More common
Night pain / Heart burn Less common More common
Age > 60 years 25 – 50 years
Relationship of pain to antacids Relief of pain not consistent Prompt relief of pain
Relationship of pain to food Relationship of pain to food Relieves the pain
Hematemesis / Melena Hematemesis MC Melena MC
Vomiting / Weight loss MC LC
Complication Risk of malignant change No malignant change
Q. ZOLLINGER-ELLISON SYNDROME / GASTRINOMA
Hypergastrinemia caused by cancer of Gastrin-producing cells
Gastrinoma → massive acid production → hyperacidity → multiple peptic ulcers (stomach, duodenum, jejunum)
Clinical features
 Refractory Ulcers
 Steatorrhea (due to inactivated lipase from large volume of acid passed into duodenum)
Differential diagnosis [Other causes of increased gastrin]
 Pernicious anemia
 Chronic gastritis
 Renal failure
 Hyperthyroidism
Complications
 Perforation
 Bleeding
o Gastroduodenal artery → source of bleeding in duodenal ulcer
o Left gastric artery → source of bleeding in gastric ulcer.
 Metastasis
 Pancreatitis (due to posterior penetration of ulcer)
Diagnosis
 Elevated Serum gastrin level → is indicative of ZES [patients on H2 blockers or PPIs have elevated gastrin]
 Gastric pH < 4
 Secretin stimulation test → positive (abnormal) → there is a rise in gastrin level after injection of secretin
o (Normally, secretin should suppress gastrin release)
 Somatostatin receptor scintigraphy
 Endoscopic U/S
 CT & MRI
Management
 Localized disease is surgically resected
 Metastatic disease is treated with the long-term administration of PPIs [to block acid production]

INFLAMMATORY BOWEL DISEASE

Results from inappropriate mucosal immune responses to normal gut flora
Epidemiology
 MC in females
 MC in developed countries
 Hygiene hypothesis - reduced mucosal immune response caused by reduced frequency of normal enteric
infection due to improved food storage/quality
It comprises two disorders
 Crohn’s disease (regional enteritis) → Transmural inflammation is seen
 Ulcerative colitis → Inflammation confined to mucosa & submucosa
Pathogenesis
 IBD results due to
o Host interactions with Gastrointestinal flora
o Intestinal epithelial dysfunction
o Aberrant mucosal immunity
Q. CROHNS DISEASE
Chronic, Transmural, Non-Caseating Granulomatous inflammation of Intestine
Sites
 Terminal Ileum – MC
 Esophagus, Stomach, Duodenum, Jejunum
 Colon
 Rectum is spared
Etiology
 Infectious – Mycobacterium paratuberculosis
 Immunological – associated with HLA-DR 1
 Environmental
 Smoking
 Diet and Food allergy
 Bacterial dysbiosis – aggressive T cell response to specific components of intestinal microbes
Pathology
Multiple areas of Transmural inflammation (Skip lesions)

Granuloma formation with serpentine ulcers

Sparing of interspersed mucosa (cobblestone appearance)

Thickening of Bowel wall (String sign of Kantor)

Formation of Stricture, Fissure, Fistula

Clinical features
 Diarrhoea, RLQ pain
 Malabsorption & Malnutrition
 Loss of albumin (protein losing enteropathy)
 Iron deficiency anaemia
 B12 deficiency anemia
 Extraintestinal manifestations
o Skin – Erythema Nodosa
o Eye – Uveitis
o Joints – Arthritis, Ankylosing spondylitis
o Kidney – Nephrotic syndrome
o Sclerosing cholangitis
o Gallstones
o Amyloidosis
o Blood – Anemia
Complications
 Stricture
 Perforation, Bleeding
 Fistula formation
 Colonic Adenocarcinoma
Differential diagnosis
 Radiation enteritis
 Ulcerative colitis
 Intestinal TB, Salmonella, Shigella
 Carcinoma Caecum
 Ectopic kidney
Investigations
 Plain X-ray
 US abdomen
 Barium meal study → Terminal ileum stenosis (string sign of Kantor)
 CT scan
 Colonoscopy
o Serpentine ulcers
o Skip lesions
o Cobblestone appearance
 Capsule endoscopy
 MRI Enteroclysis – demonstrate fistula
 Screening test – presence of ASCA [anti-saccharomyces cerevisiae antibody]
Treatment
 TPN
 Drugs
o Steroids – induces remission
o Azathioprine – immunosuppression
o Infliximab – monoclonal antibody
 Surgical treatment
o Ileocaecal resection
o Right hemicolectomy
o Total colectomy & Ileorectal anastomosis
Q. ULCERATIVE COLITIS
Inflammatory condition of Rectum & Colon
Starts in Rectum, spreads proximally to Colon (Pancolitis) & ileum (Back Wash Ileitis)
Etiological factors
 Red meat
 Immunological – associated with HLA-DR 2
 Allergy to dietary factors
 Stress, Smoking, Alcohol
 Defective mucin production in colonic mucosa
Appendectomy & Smoking protective against ulcerative colitis \
Pathology
Mucosal and submucosal inflammation

Extensive ulceration (No skip lesions)

Stricture of colon

Permanently contracted colon (Lead Pipe appearance)

Epithelial thickening between the ulcers (Pseudopolyposis)

Clinical features
 Bloody mucoid diarrhea
 Tenesmus
 RLQ pain
 Abdominal distention
 Severe Malnutrition & Hypoproteinemia
 Extraintestinal manifestations
o Uveitis
o Ankylosing spondylitis
o Sclerosing cholangitis

Complications
 Pseudopolyposis
 Colonic adenocarcinoma
 Stricture
 Massive hemorrhage
 Toxic megacolon

Differential diagnosis
 Crohn’s disease
 Bacillary dysentery
 Carcinoma colon
 Infectious colitis – Campylobacter jejuni
Investigations
 Plain X-ray
o Obstruction
o Toxic megacolon
o Perforation
 Barium enema → Lead pipe appearance
 Sigmoidoscopy & biopsy
 Colonoscopy
Treatment
 TPN
 Correction of anemia
 Drugs
o Steroids – induces remission
o Azathioprine – immunosuppression
o Infliximab – monoclonal antibody
o Mesalamine – anti-inflammatory
 Surgery
o Total Procto-Colectomy with Ileo-Anal Anastomosis
o Total Proctectomy with Ileostomy
Q. WHIPPLE'S DISEASE.
Chronic multisystem disease associated with malabsorption
Involves Multiple Organ systems [GIT, Joints, Eye, Brain, Skin, Heart]
Etiology
 Gram-positive bacteria, Tropheryma whippelii
Pathogenesis
Endocytosis of Bacteria into macrophages in small intestine

These macrophages cause lymphatic blockade in lamina propria of small intestine causing malabsorption.
Clinical Features
 Diarrhea
 Chronic migratory, non-destructive polyarthritis
 Weight loss
 Abdominal pain, distension and tenderness
 Ophthalmoplegia
 Neurologic features (dementia, myoclonus).
 Generalized lymphadenopathy
 Skin pigmentation
 Cardiac involvement [mitral & aortic regurgitation]
Investigations
 Elevated ESR & CRP
 Tests for malabsorption.
 Jejunal biopsy
 Biopsy of other involved tissues → PAS positive macrophages that contain small bacilli.
 PCR tests for T. whippelii Ag in saliva, stool or joint fluid.
Treatment
IV Ceftriaxone / Meropenem (2 g daily) 2-week course

Followed by Oral Trimethoprim - Sulphamethoxazole BID 1 year

Q. ABDOMINAL TUBERCULOSIS
Tubercular involvement of Gut, Abdominal Lymph Nodes, Peritoneum
Intestinal tuberculosis commonly affects ileocecal region due to
 Increased physiological stasis
 Increased rate of fluid & electrolyte absorption
 Minimal digestive activity
 Abundance of lymphoid tissue
Etiology → M. tuberculosis
Routes of Spread
 Intestinal tuberculosis
o Hematogenous spread from the primary lung focus
o Ingestion of bacilli in sputum
o Direct spread from adjacent organs
o Lymphatic spread from infected nodes
 Peritoneal tuberculosis
o Spread from lymph nodes
o Spread from intestinal lesions
o Spread from tubercular salpingitis in females
Pathology
 3 Types
o Ulcerative
o Hypertrophic
o Ulcero-Hypertrophic
Clinical Features
 Fever
 Pain
 Diarrhea
 Constipation
 Weight loss
 Anorexia
 Abdominal distention
 Palpable mass usually in Right Iliac region
Complications
 Haemorrhage
 Perforation
 Subacute intestinal obstruction
 Fistula formation (between skin & intestine or between loops of intestines)
 Malabsorption (ileocecal tuberculosis MC cause of malabsorption in India)
Differential Diagnosis
 Tropical sprue
 Amoebiasis
 Worm infestation
 Lymphoma
 Crohn's disease
 Colonic malignancy
Investigations
 Raised ESR
 CXR → Active or Old TB lesion
 Abdomen X-ray
o Calcified lymph nodes
o Dilated bowel loops with multiple air-fluid levels due to obstruction
o Air under diaphragm
 Barium meal
o Hypermotility (accelerated intestinal transit)
o Hyper-segmentation of barium column ("chicken intestine")
o Multiple strictures with Segmental dilatation of bowel loops
o Stierlin sign → failure of diseased segment to retain barium
o String sign → thin stream of barium seen in the terminal ileum
 Barium enema.
o Inverted umbrella sign → Wide gaping of ileocecal valve with narrowing of terminal ileum
o Goose neck deformity → Loss of normal ileocecal angle
 Abdominal ultrasound
 Contrast-enhanced CT scan
 Ascitic fluid examination
 Colonoscopy
Treatment
 Antitubercular treatment
 Surgery
o Strictureplasty
o Treatment of perforation
Q. IRRITABLE BOWEL SYNDROME
Chronic symptom complex of altered bowel habits & abdominal pain without any Organic cause
Etiology
 Anxiety
 Stress
 Altered GI motility
Clinical Features
 At least 3 months of continuous or recurrent symptoms of abdominal pain or discomfort which is
o Relieved with defecation
o Associated with change in frequency of stool
o Associated with a change in consistency of stool
Investigations
 Stool Examination for
o Leukocyte
o Ova
o Parasites
o Bacteria
 Sigmoidoscopy
 Barium enema examination
 Upper GI and small-bowel endoscopy
 Ultrasound of gallbladder
 Abdominal CT scan
Management
 Reassurance
 Stress reduction
 Low dose TCA
 Increase the dietary fiber
 Antidiarrheal agents

Q. VIRCHOW’S NODE
 a.k.a Left supraclavicular node
 Palpable in GIT malignancy & pelvic malignancy (Trousier’s sign)
Q. UPPER GASTROINTESTINAL ENDOSCOPY
Indications
 Dysphagia
 Caustic or foreign body ingestion
 Dyspepsia
 Persistent nausea & vomiting
 Small intestine biopsy
 Acute or Chronic gastrointestinal bleeding
 Inflammatory bowel disease (may be associated with duodenal lesions mimicking a duodenal ulcer)
 Chronic abdominal pain
 Suspected polyp or cancer.
Contraindications
 Suspected Perforation
 Patient in shock
 Uncooperative patient
 Severe inflammatory bowel disease or toxic megacolon (colonoscopy)
Complications
 Perforation
 Bleeding
 Cardiac arrhythmias
 Reaction to medication (sclerosants)
 Vasovagal reaction
 Pulmonary aspiration

Q. PLUMMER-VINSON SYNDROME FEATURES a.k.a PATTERSON-KELLY SYNDROME

 Dysphagia initially to solids later to liquids [due to Esophageal webs]
 Iron deficiency [Microcytic hypochromic anemia]
 Koilonychia
 Atrophic Glossitis
 Increased Risk of Post-Cricoid Carcinoma
Q. TROPICAL SPRUE (IDIOPATHIC TROPICAL MALABSORPTION SYNDROME)
Malabsorption occurring in patients of tropics in the absence of other intestinal diseases or parasites.
Etiology
 Infective organism [E. coli, Klebsiella & Enterobacter]
 Folic acid deficiency
Clinical Features
 Three phases:
o Initial phase of active diarrhoea (common in India)
o Intermediate phase
o Last phase (frank malabsorption)
 Diarrhea
 Abdominal distension
 Anorexia
 Weight loss
 Megaloblastic anemia, glossitis and stomatitis
Investigations
 Stool examination → for Pathogens
 Megaloblastic anemia
 Hypoalbuminemia
 Impaired tests of absorption
 Jejunal biopsy → Partial villous atrophy
Treatment
 Tetracycline 1 g daily for 6 months
 Folic acid 5 mg daily (along with tetracycline)
 Correction of deficiencies of fluids, electrolytes, vitamins and iron
 Symptomatic treatment for diarrhea
Q. COELIAC DISEASE (NON-TROPICAL SPRUE; GLUTEN-INDUCED ENTEROPATHY)
Chronic intestinal disease causing malabsorption due to gluten intolerance
Etiology
 Immunological damage of mucosa due to gluten protein [gliadin] of wheat, barley and rye.
 Association with HLA DQ2 & DQ8
Clinical features
 Chronic diarrhea or steatorrhea
 Abdominal pain & Bloating
 Pruritic rash on extensor surfaces (dermatitis herpetiformis)
 LFT abnormalities
 Unexpanded iron deficiency anemia
 Fat-soluble vitamin deficiencies
 Early onset osteoporosis
 Strong association with type 1 diabetes)
Investigations
 Serologic tests
o IgA anti-endomysial antibodies
o IgA antitissue transglutarninase antibodies
o lgG & lgA antigliadin antibodies
 Jejunal biopsy → Partial villous atrophy
 Tests of Absorption
Treatment.
 Gluten-free diet (no wheat, oats, rye, barley, beer)
 Dapsone → dermatitis herpetiformis.
 Vitamin & Mineral supplementation
HEPATOLOGY
BILIRUBIN METABOLISM AND BILE FORMATION

Unconjugated bilirubin → Lipid soluble & Water insoluble & Tight bond with serum Albumin [Not excreted in urine]

Conjugation [uridine diphosphate (UDP)–glucuronyl-transferase (UGT1A1)]

Conjugated bilirubin → Lipid insoluble & Loose soluble & Tight bond with serum Albumin [Not excreted in urine]

Kernicterus: Irreversible brain injury due to high concentrations of free unconjugated bilirubin crossing B-B barrier
Presence of urobilinogen in urine rules out obstructive jaundice.
Q. JAUNDICE
Yellowish pigmentation of skin, mucous membranes & sclera due to increased levels of bilirubin
Normal serum bilirubin level → 0.3 to 1.2 mg/dL.
Jaundice serum bilirubin level → > 2.0–2.5 mg/dL
Mechanism of Jaundice
 Unconjugated hyperbilirubinemia
o Excessive extrahepatic production of bilirubin
 Hemolytic anemias
 Internal hemorrhage (GI bleeding, Hematomas)
 Ineffective erythropoiesis (Pernicious anemia, Thalassemia)
o Reduced hepatocyte uptake
 Drug interfering with membrane carrier systems
 Diffuse liver disease (Hepatitis, Cirrhosis)
o Impaired conjugation
 Physiologic jaundice of the newborn
 Crigler–Najjar syndrome types I and II
 Gilbert syndrome
 Conjugated hyperbilirubinemia
o Decreased hepatocellular excretion
 Deficiency of canalicular membrane transporters
 Dubin–Johnson syndrome
 Rotor syndrome
 Liver Damage or Toxicity
o Impaired bile flow
 Inflammatory destruction of bile ducts
 Gallstones
 Carcinoma of pancreas
Classification
 Hemolytic (prehepatic)
 Hepatocellular jaundice (hepatic)
 Obstructive (post-hepatic)

Clinical features
Clinical feature Hemolytic Hepatocellular Obstructive
Color of jaundice Lemon yellow Orange yellow Greenish yellow
Pruritus Absent Variable Present
Bleeding tendency Absent Present Present (late)
Bradycardia Absent Absent Present
Anemia / Pallor Present Absent Absent
Splenomegaly Present Variable After cirrhosis
Gallbladder Not palpable Not palpable Palpable
Features of Hepatic failure Absent Present (early) Present (late)
Absence of bile in bowel in case of Hepatocellular & Obstructive Jaundice → impairs absorption of
 Fat – steatorrhea
 Vit A - visual problems
 Vit D – osteomalacia
 Vit E – peripheral neuropathy, cerebellar ataxia
 Vit K – bleeding tendencies

Investigations
Investigations Hemolytic Hepatocellular Obstructive
Serum bilirubin Unconjugated Unconjugated Conjugated
AST & ALT Normal Grossly elevated Slightly elevated
ALP Normal Slightly raised Grossly elevated
Coomb’s test Positive - -
Osmotic fragility Increased - -

Other Investigations
 ERCP – endoscopic retrograde cholangiopancreatography
 MRCP - Magnetic resonance cholangiopancreatography
 Tumor markers – CA 19/9
 Endoscopic US
 Intraductal US
 CT/MR angiogram
 Urine tests - Hays test, Fouchet’s test
Q. MANAGEMENT OF ACUTE VARICEAL BLEEDING

Endoscopic therapy
 Endoscopic variceal band ligation
 Endoscopic gluing using tissue adhesives (Butyl cyanoacrylate)
 Endoscopic variceal sclerotherapy using
o Ethanolamine
o STDS – sodium tetradecyl sulphate
Shunting surgeries
 Trans-jugular- Intrahepatic Porto-systemic shunt
 Conventional splenorenal shunt

Q. LIVER BIOPSY
Indications
 Cirrhosis
 Hepatic malignancy
 Chronic hepatitis
 Storage & Metabolic disorder [Amyloidosis, Glycogen Storage Disorders, Haemochromatosis, Wilson's Disease]
 Pyrexia of unknown origin (associated with hepatomegaly)
Q. SPONTANEOUS BACTERIAL PERITONITIS
Infection of Ascitic fluid in Cirrhotic patient in absence of recognizable secondary cause of peritonitis
Mode of infection
Bacteria from GIT Bacteria from elsewhere
 Streptococcus faecalis  Gonococcus - fallopian tube
 Staphylococcus  Mycobacterium - pulmonary TB
 E. Coli  Chlamydia – vaginal Infection
 Klebsiella
 Cl. Welchii

Clinical features
 Sudden onset severe pain
 Fever, Vomiting
 Blumberg sign - rebound tenderness
 Tachycardia, Tachypnea
 Abdomen distension
 Hypocrates facies
o Sunken eyes & temples
o Pinched nose
o Tense hard skin
 Absent bowel sounds due to paralytic ileus
 Septicemia – SIRS & MODS
Differential diagnosis
 Pancreatitis
 Intestinal obstruction
 Ruptured ectopic pregnancy
 Acute pyelonephritis
 Acute mesenteric ischemia
 Diabetic acute abdomen
Investigations
 X-ray abdomen
o Ground glass appearance
o Gas under the diaphragm
 US abdomen
 Electrolyte study
 Blood culture
 Diagnostic peritoneal lavage -> 500 WBC / ml suggests peritonitis
 Diagnostic laparoscopy
 CT/MRI
Treatment
 Primary assessment and resuscitation → ABC
 Systemic antibiotic therapy
o 3rd gen cephalosporins [Cefotaxime 2 g IV 8 hourly for 5 days]
o Piperacillin & Tazobactam
o Meropenem, Imipenem
 Electrolyte management
 Percutaneous USG or CT guided drainage
 Laparotomy drainage
Q. PORTAL HYPERTENSION
Sustained elevation of portal venous pressure > 10 mmHg (normally 5-10 mmHg)
Or
Elevation of hepatic venous pressure gradient- HVPG > 5 mmHg
 HVPG > 5 mmHg - portal hypertension
 HVPG > 10 mmHg – Porto-systemic shunt opens
 HVPG > 12 mmHg – esophageal variceal bleeding
Causes
Prehepatic Hepatic Posthepatic
Portal vein thrombosis Alcoholic cirrhosis Budd-Chiari syndrome
Spleenic vein thrombosis Schistosomiasis Congestive cardiac failure
Periportal inflammation Hepatitis Constrictive pericarditis
Hypercoagulable state Wilson's disease
Hemochromatosis

Clinical presentation
 Triad of portal hypertension
o Esophageal varices
o Splenomegaly
o Ascites
 Hypersplenism
 Haemorrhoids
 Caput medusa
 Coagulopathy
 Kenawys sign – venous hum in epigastrium, heard louder on inspiration
 Hepatic encephalopathy
o Memory loss
o Asterixis (flapping tremor/liver flap)
 Hepatorenal syndrome
o Decreased urine output
o Renal failure

Investigations
 Hb% - Anaemia due to Bleeding & Hypersplenism
 LFT
o Raised Bilirubin
o Raised PT
o Raised aPTT
 RFT – Raised Blood Urea, Serum Creatinine
 USG abdomen – Splenomegaly
 Contrast CT and MRI – Collateral Circulation
 MR venogram – Extrahepatic Portal Vein Thrombosis
 HVPG – Gold Standard
 Esophago-Gastroscopy – identify bleeding varices
Management
 General measures
o Correction of anaemia
o Nutrition supplementation
o Inj Vitamin K – coagulopathy correction
o Blood transfusion
 Specific Treatment for
o Hepatic encephalopathy
o Ascites
o Esophageal Varices
o Reduce portal pressure  Porto-Systemic shunt

Q. HYPERSPLENISM
Overactivity of spleen resulting in Pancytopenia & Hypercellular Bone Marrow
Causes
 Primary hypersplenism
 Portal hypertension
 Infection – Malaria, TB, Kala-azar
 Myeloproliferative disorders
Clinical features
 Transfusion dependent anaemia
 Recurrent infection
 Spontaneous bleeding episodes – Epistaxis, Bleeding Gums
Investigation
 Peripheral blood smear, Bone marrow aspirate smear
 LFT
 US abdomen
Treatment
 Splenic artery embolization
 Splenectomy
Q. NON-ALCOHOLIC FATTY LIVER DISEASE / NON-ALCOHOLIC STEATOHEPATITIS
Steatosis with Hepatocellular Ballooning & Lobular Inflammation in absence of significant alcohol consumption
NASH is associated with
 Insulin Resistance
 Metabolic Syndrome
 DM
 HTN
 Dyslipidaemia
 Obesity
Complications
 Cryptogenic cirrhosis (cirrhosis of uncertain etiology)
 Fibrosis
 End Stage Liver Disease
Diagnosis
 Elevated aminotransferases (ALT > AST)
 Liver biopsy showing
o Macrovesicular steatosis
o Mallory hyaline changes
o Perivenular & Perisinusoidal fibrosis
Treatment
 Correct obesity by Diet Control & Exercise
 Thiozolidinediones to improve insulin sensitivity in DM
 Treat Hyperlipidaemia with Statins
 Liver transplantation for End Stage Liver Disease

SAFE WEEKLY LIMITS OF ALCOHOL

Males  21 units
Females  14 units
(1 unit = 10 gm of alcohol, 30 ml of whisky, 100 ml of wine, 250 ml of beer).
Cirrhogenic dose  180 gm of ethanol/day for 25 years, i.e. 6 times the safety limit

ALCOHOLIC LIVER DISEASE  SYNDROMES

Liver injury due to Chronic & excessive ingestion of alcohol
 Fatty liver
 Alcoholic hepatitis
 Alcoholic cirrhosis
Q. CIRRHOSIS OF LIVER
Irreversible chronic injury of Hepatic Parenchyma leading to Extensive Fibrosis & formation of regenerative nodules.
< 3 mm (micronodules)
> 3 mm (macronodules).
Etiopathological Classification
 Alcoholic / Laennec’s
 Post-Necrotic / Post-viral
o HBV, HCV infections
o Chronic active hepatitis.
o Drugs & Toxins. (Methotrexate, Methyldopa, Isoniazid, Sulphonamides)
 Biliary
o Primary BC.
o Secondary BC
 Cardiac
o Right Sided congestive heart
o Tricuspid insufficiency
o Constrictive Pericarditis.
 Metabolic
o Haemochromatosis
o Wilson’s disease
o α1 AT deficiency
o DM
o Galactosaemia
o Tyrosinosis
o Fanconi’s syndrome
o Hereditary Fructose intolerance
o Type IV Glycogen Storage Disease
 Miscellaneous
o Hepatic venous outflow obstruction
 Veno-occlusive disease
 Budd-Chiari syndrome.
o Intestinal bypass, Gastroplasty
o Indian childhood cirrhosis/malnutrition
o Syphilis in neonates
o Cystic fibrosis
o Schistosomiasis
o NASH

Morphological Classification
 Micronodular cirrhosis (Laennec’s cirrhosis)
 Macronodular cirrhosis (Post-Necrotic / Post-viral)
 Mixed type
Clinical Features
• Symptoms
• Low-grade fever.
• Weakness, Fatigue & Weight Loss.
• Anorexia, Nausea, Vomiting & upper abdominal discomfort.
• Abdominal distension due to Ascites & Gas.
• Loss of Libido.
• Menstrual irregularities
• Haemorrhagic tendencies  Bruising, Purpura, Epistaxis, Menorrhagia & GI bleeding.
• Haemorrhagic tendencies
 Decreased production of Coagulation factors by Liver
 Thrombocytopenia due to Hypersplenism.
• Symptoms of Hepatic Insufficiency
• Symptoms of Portal Hypertension
• Signs of Hepatocellular failure
• Features dominant in Male Cirrhotics (due to Hyperestrogenism)
 Diminished body hair
 Gynaecomastia
 Testicular atrophy
• Features dominant in alcoholic cirrhosis
 Parotid enlargement
 Clubbing
 Spider naevi  Arteriolar changes by Hyperoestrogenism, Seen in areas drained by SVC
 Dupuytren's contractures  Fibrosis of Palmar Aponeurosis by Local Microvessel Ischaemia
 White / Terry’s nails  Due to Hypoalbuminemia
 Muehrcke's nails  Pairs of Transverse White Lines (disappear on applying pressure)
 Palmar Erythema  due to Increased Peripheral Blood Flow & Decreased Visceral Blood Flow
 Flapping tremors  Hepatic Encephalopathy
 Ascites  due to Portal HTN
• Features dominant in Female Cirrhotics
 Menstrual Irregularities
 Signs of Virilisation
 Breast Atrophy.
Complications of Cirrhosis
 Portal hypertension
 Ascites
 Hepatic encephalopathy
 Spontaneous bacterial peritonitis
 Hepato-renal syndrome
 Hepatocellular carcinoma
 Coagulopathy
 Hepato-Pulmonary syndrome  Hypoxia due to intrapulmonary arteriovenous shunting  VQ mismatch
 Malnutrition.
 Bone disorders—Osteopenia, Osteoporosis, Osteomalacia
 Haematological—Anaemia, Neutropenia, Thrombocytopenia, Haemolysis.
Investigations
 Complete blood picture
 Liver function tests
 Hyperbilirubinaemia (Mixed type)
 A:G ratio reversal.
 Serum albumin decreased (impairment of hepatic protein synthesis)
 Serum globulin increased (non-specific stimulation of reticuloendothelial system)
 Transaminases
 AST (SGOT) is raised.
 ALT (SGPT) is raised, but less than 300 units.
 AST:ALT ratio > 2 in Alcoholic Cirrhosis
 AST:ALT ratio > 2 in viral hepatitis
 Alkaline phosphatase  mildly raised
 Prothrombin time  Prolonged
 Hepatitis B - C markers .
 Blood ammonia Raised in Hepatic Encephalopathy.
 Metabolic abnormalities
 Glucose intolerance
 Hyponatraemia
 Hypokalaemia
 Hypomagnesaemia
 Hypophosphataemia.
 Ultrasonographic examination
 Macronodules
 Ascites.
 Splenomegaly
 Fibroscan  determine amount of fibrosis.
 Liver biopsy  Confirms diagnosis of cirrhosis
 Ascitic fluid examination
Treatment
 Treatment of underlying causes.
 Diet
o High-protein diet-minimum 1 g/kg/day.
o 2000--3000 kcal/day.
o Diets enriched in Branched-Chain amino acids, in patients predisposed to hepatic encephalopathy.
o Multivitamin supplementation
 Vaccination against Hepatitis A & B viruses, Influenza Virus & Pneumococcus
 Specific treatment of complications
Q. HEPATOCELLULAR CARCINOMA / HEPATOMA
Primary malignant tumor of liver with Hepatocellular Differentiation
Risk factors
 Infection – Hep B, Hep C
 Cirrhosis
 Environmental – Aflatoxins, Pyrrolizidine
 Metabolic – hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency
Clinical features
 Right hypochondriac pain
 Palpable mass in Right Hypochondrium & Epigastrium
 Weight loss
 Jaundice
 Ascites, Massive spleenomegaly
 Gastrointestinal bleeding - due to Portal HTN
Spread of tumor
 Lymphatic spread
 Hematogenous spread
 Direct infiltration
Differential diagnosis
 Secondaries in liver
 Hepatosteatosis
 Hydatid cyst
 Amoebic liver abscess
 Cholangiocarcinoma
Investigations
 US abdomen – Hyperechoic Mass, Mosaic pattern
 CT scan abdomen – Size, Location, Portal vein invasion
 Tumor markers – Alpha-Fetoprotein
 CT angiography – Arterial pattern of tumor
Treatment
 Non-surgical strategies
 Transarterial Chemotherapy
 Transarterial embolization
 External Beam radiotherapy
 Percutaneous ethanol/acetic acid injection
 Surgical procedures
 Hemi hepatectomy
 Total hepatectomy
 Liver transplantation.
Q. HEPATIC COMA (HEPATIC ENCEPHALOPATHY)
Complex Neuropsychiatric Syndrome characterized by
 Disturbances in Consciousness & Behaviour
 Personality changes
 Fluctuating Neurological signs
 Asterixis
 Distinctive Electroencephalographic changes.
Types
 Acute / Subacute  Reversible
 Chronic  Irreversible
Precipitating Factors
 Increased nitrogen load
o GE bleeding
o Excessive Dietary Protein
o Uremia
o Constipation
 Electrolyte imbalance
o Hypokalaemia
o Alkalosis
o Hypoxia
o Hypovolaemia
 Drugs
o Narcotics
o Tranquilizers
o Sedatives
o Diuretics
 Others
o Infection
o Surgery
o Acute & Progressive Liver Disease
 Large binge of alcohol.
 Large volume of Paracentesis.
 TIPS.

Pathogenesis
Abnormality in Nitrogen Metabolism

Ammonia formed in bowel by action of Urease Containing Organisms

Carried in Portal Circulation to Liver

Failure of detoxification due to Hepatocellular Disease or Portal HTN

Substances enter Systemic Circulation interfere with Cerebral Metabolism

Clinical Features
 Derangement of consciousness,
 Altered Sleep rhythm
 Increased psychomotor activity
 Progressive Drowsiness, Stupor
 Asterixis
 Fetor hepaticus  musty odour of breath due to mercaptans
 Extrapyramidal signs.
o Exaggeration of DTR
 Coma.
Diagnosis (diagnosis of exclusion)
 No Pathognomonic Liver Function abnormality
 Elevation of serum ammonia
 CSF analysis is normal
 CT scan of brain does not show any abnormality
 EEG (reduced alpha rhythm & increased delta activity)
Treatment
 Elimination of precipitating factors.
 Nasogastric aspiration (in case of bleeding)
 Protection of airway (Endotracheal tube)
 Avoid Constipation (bowel wash, enema, Lactulose)
 Bowel sterilisation (Neomycin 1 gm QID)
 Protein is restricted
 IV Mannitol  reducing Cerebral Edema
 Zinc supplementation is sometimes helpful.
 Liver transplantation.

Q. ACUTE VIRAL HEPATITIS

Mode of transmission
• Parenteral, Sexual, Saliva  Hepatitis B, C, D virus
• Feco-Oral route  Hepatitis A, E virus.
• Percutaneous  Hepatitis G virus.
Complications
• Fulminant hepatic failure
• Cholestatic hepatitis
• Hyperbilirubinaemia (in Gilbert’s syndrome)
• Renal failure
• Henoch-Schonlein purpura
• Chronic hepatitis (HCV, HBV)
• Cirrhosis (HBV, HCV, HDV)
• Hepatocellular carcinoma (HBV, HCV)
• Aplastic anaemia
• Pancreatitis, Myocarditis
• Transverse myelitis
Clinical features

Investigations
• Elevated AST, ALT
• Hyperbilirubinaemia
• PT raised.
• Serological tests
o HAV  Anti-HAV IgM or Anti-HAV IgG
o HBV
 HBsAg  appears before the onset of symptoms, marker of active Infection
 HBeAg, HBV-DNA & DNA polymerase  markers of Active Viral Replication.
 IgM Anti-HBc  first antibody to appear
 IgM Anti-Hbe  second antibody to appear, Suggests Recovery
 Anti-HBs  confers protection against subsequent infection.
o HDV  HDAg & IgM or IgG Anti-HDV.
o HCV  ELISA for
 Anti-C100-3 Ab
 C22-3 Ag
 NS 3 Ag
 NS 5 Ag
Treatment
• Bed rest
• Supportive therapy
• Nutritious diet.
• Acute HBV  Lamivudine at 100 mg/d orally
• Acute HCV  Pegylated IFN-α
• FHF  Liver transplantation
Q. HEPATORENAL SYNDROME
Progressive functional renal failure in patients with severe liver disease.
Precipitating factors:
• SBP
• Large volume of paracentesis without volume expansion
Pathogenesis
Defective clearance of vasoconstrictor substances by Liver (Angiotensin, Thromboxanes, Kinins, Endothelin-1)

Intra-renal vasoconstriction

Hepatorenal syndrome
Two types
• Type I: Rapidly progressive (< 2 weeks)
• Type II: Slowly progressive.
Criteria for Diagnosis
• Major criteria
o Chronic or Acute liver disease with Hepatic Decompensation
o Low GFR (S creatinine > 1.5 mg%)
o Absence of Treatment with Nephrotoxic drugs, Shock, Infection or Signicificant fluid loss
o No sustained improvement in renal function after Diuretic Withdrawal & Volume Expansion
o No USG evidence of Obstructive or Parenchymal Renal Disease.
• Additional criteria
o Urine volume < 500 ml/d
o U. Na+ < 10 mEq/litre
o U osmolality > Plasma osmolality
o Urine RBC < 50/HPF
o S. Na+ < 130 mEq/litre.
Management
• Removal of Precipitating factors
o Diuretics stopped
o Blood volume replenished
o Infections treated
o Avoid nephrotoxic drugs.
• Drugs
o Midodrine (α agonist) + Octreotide + IV Albumin
• TIPS
• Liver transplantation
Q. HEPATOPULMONARY SYNDROME
Characterised by
• Advanced chronic liver disease
• Arterial hypoxaemia (decreased PaO2)
• Intra-pulmonary vasodilatation (Decreased clearance of vasodilator substances by Liver)
• No primary cardio-pulmonary disorder
Clinical Features
• Dyspnoea in upright posture (Platypnoea)
• Oxygen desaturation in upright position (Ortho-deoxia)
Investigations
• Contrast enhanced ECHO
• Technitium Tc99 macro-aggregated albumin lung perfusion scan
Treatment
• Oxygen supplementation
• Almitrine, Garlic  to increase Pulmonary Vascular Resistance
• TIPS
• Liver transplantation
Q. CHRONIC HEPATITIS (CH)
Biochemical or Serologic evidence of continuing inflammatory hepatic disease for > 6 months, with symptoms
Causes of Chronic Hepatitis
• Viral (HBV, HCV, HDV)
• Drugs (alpha-methyldopa, isoniazid)
• Alcoholic liver disease
• Non-alcoholic steatohepatitis
• Metabolic causes
o Primary biliary cirrhosis
o Sclerosing cholangitis
o Alpha-1-antitrypsin deficiency
o Wilson’s disease
o Haemochromatosis
• Autoimmune hepatitis
o Type I (antiactin/lupoid)
o Type II (anti-liver kidney microsomal)
o Type III (anti-soluble liver antigen)
• Cryptogenic
Staging
• Stage 0 - No fibrosis
• Stage 1 - Mild fibrosis
• Stage 2 - Moderate fibrosis
• Stage 3 - Severe fibrosis
• Stage 4 – Cirrhosis
Q. WILSON’S DISEASE
Autosomal recessive disorder
ATP7B gene mutation in Chromosome 13  Absence/Deficiency of serum Ceruloplasmin (Copper transporter)

Clinical Features
• Age 6-20 years
Investigations
• Serum ceruloplasmin  Low
• Total serum copper  Decreased
• Free copper  Elevated
• Urine copper excretion  Elevated
• Liver biopsy Hepatic copper concentration > 250 µg/gm
• Kayser-Fleischer ring  slit-lamp examination.
• Aminotransferase  Elevated
• Radiocopper loading test
Treatment
• Low copper diet
• Trientine & Zinc therapy
• Hepatic transplantation
Q. HAEMOCHROMATOSIS
Excessive iron absorption leading to progressive increase in total body iron stores
Classification
Primary Parenteral iron overload Secondary
ATP7A gene mutation in Chromosome 6 • Multiple blood transfusions • Refractory anaemia
• Excessive parenteral iron • Chronic liver injury
• Haemodialysis • Dietary iron overload
• Porphyria cutanea tarda
Clinical features

Investigations
• Serum iron  Elevated
• TIBC  Elevated
• Serum ferritin  Elevated
• Transferrin saturation  Increased
• Liver biopsy  Hepatic iron concentration > 1000 µg/100 mg  suggests Hemochromatosis
• CT scan  increased CT density
Management
• Phlebotomy
• Desferrioxamine  40–80 mg/kg/day, subcutaneously. It
• Oral Deferasirox  Thalassemia & Secondary Iron Overload.
• Avoid alcohol.
• ESLD  Liver transplantation
Q. LIVER FUNCTION TESTS
• Serum Bilirubin  both direct & indirect bilirubin (Van-den-Bergh’s test)
• Serum Albumin, Globulin, A:G ratio
• PT – normal value 12-16 seconds, if altered corrected by IM Vitamin K
• ALP → indicates Secretory functions
• AST/SGOT → indicates inflammation
• ALT/SGPT – specific to Liver
• 5-nucleotidase, Gamma glutamyl transpeptidase (GGT)
• Alpha-Fetoprotein
• Technetium 99 scan – shows uptake and excretion of bile
• Urine bile salt test (Hays test)
• Urine bile pigments (Fouchet’s test)
Hepatocyte function → AST, ALT
Synthetic function → PT, Albumin, Bilirubin, Factor 5, 7
Biliary canalicular function – ALP, 5 nucleotidase, GGT
Other investigations for liver disease
• US abdomen
• ERCP/MRI/CT/PTC. (Percutaneous transhepatic cholangiography)
• Laparoscopy
• Liver biopsy

Q. CAUSES OF PAINFUL / TENDER HEPATOMEGALY

 Congestive cardiac failure
 Viral hepatitis
 Hepatic amoebiasis
 Pyemic abscess
 Hepatoma
 Actinomycosis
 Secondaries
 Budd-Chiari syndrome.

Q. CAUSES OF PULSATILE LIVER

 Tricuspid regurgitation (systolic)
 Tricuspid stenosis (diastolic)
 Aortic regurgitation

Q. MEIG’S SYNDROME (Ovary, Abdomen, Lung)

 Ovarian Fibroma
 Ascites
 Right Sided Pleural Effusion

Q. MURPHY’S SIGN → seen in Acute Cholecystitis

Ask patient to take a deep breath while palpating Right Subcostal Area
Inflamed gallbladder comes into contact with Examiner’s hand  Pain  Mid-inspiratory arrest of Respiration
Q. BILIARY CIRRHOSIS
Two types
1. Primary biliary cirrhosis  Chronic Inflammation & Fibrous Obliteration of Intrahepatic bile ducts
 CRST syndrome (Calcinosis, Raynaud’s phenomenon, Sclerodactyly, Telangiectasia)
 Sicca syndrome
 Autoimmune thyroiditis
2. Secondary biliary cirrhosis  Partial or Complete obstruction of Extrahepatic Bile ducts
 Post-operative Strictures
 Gall stones
 Tumors
RHEUMATOLOGY AND BONE DISEASE
Q. RHEUMATOID ARTHRITIS
Chronic non-suppurative inflammation of synovial joints
Predisposing factors  HLA-DR4
Triggering Factors
 Infection
 Vaccinations
 Physical trauma
 Psychological stress

Pathogenesis
 Exposure of genetically predisposed individual to infectious agent → leads to autoimmunity → formation of
immune complexes → immune complexes deposited in synovial membrane → chronic granulomatous
inflammation of synovial membrane

Clinical features
 Acute, Symmetrical polyarthritis
o Pain & stiffness in multiple joints (at least four)
o Particularly in Morning (morning stiffness)
o MC seen in Metacarpo-Phalangeal joints, particularly that of index finger
o Other joints affected are
 MP joints of hand
 PIP joints of fingers
 Sparing of DIP joints
 Wrists, Knees, Elbows, Ankles, Hip joint
 Temporo-mandibular joint
 Atlanto-axial joint
 Facet joints of cervical spine
Examination
o Swollen boggy joints [intra-articular effusion, synovial hypertrophy]
o Deformities in Rheumatoid arthritis
 o Extra-articular manifestations

Investigations
 Radiological examination:
 Reduced joint space
 Erosion of articular margins
 Subchondral cysts
 Bloodo Elevated ESR
 Low haemoglobin value
 Rheumatoid factor [Latex fixation test, Rose-Waaler test]
 Synovial fluid examination
 Synovial biopsy Staging
 Triggering
 Maturation
 Targeting
 Fulminant stage
Differential ddiagnosis
 SLE
 Osteoarthritis
 Psoriatic arthritis
Treatment
 Drug therapy
o DMARD
 Methotrexate  7.5 mg PO weekly once
 Chloroquine
 Corticosteroids + ACTH
 Leflunomide
 Azathioprine
 Cyclophosphamide
 Cyclosporine
 Levamisole.
o NSAID.
 Aspirin
 Indomethacin
 Ibuprofen.
o Monoclonal antibodies
 Infliximab
 Adalimumab
 Etanercept
 Physiotherapy
o Joint Mobilization
o Splints.
o Walking aids
 Surgery
o Synovectomy
o Arthroplasty
o Arthrodesis.
DIAGNOSTIC CRITERIA (American College of Rheumatology)
score of > 6/10 is  definite RA
score of <6/10 not classifiable as RA
Features Score
Joint involvement
 One large joint 0
 2-10 large joints 1
 1-3 small joints 2
 4-10 small joints 3
 >10 joints (at least 1 small joint) 5
Serology
 Negative RF & Negative ACPA 0
 Low-positive RF or Low-positive ACPA 2
 High-positive RF or High-positive ACPA 3
Acute-phase reactants
 Normal CRP & Normal ESR 0
 Abnormal CRP & Abnormal ESR 1
Duration of symptoms
 <6 weeks 0
 >6 weeks 1
Q. SERONEGATIVE ARTHROPATHIES, SPONDYLOARTHROPATHIES
Group of disorders sharing certain clinical features such as
 Seronegative (ANA negative, RF negative)
 Involve Lower Back & Sacroiliac Joints
 HLA-B27
 Extraarticular manifestations
Consists of
 Ankylosing spondylitis
 Reactive arthritis
 Psoriatic arthritis
 Enteropathic arthropathy

Ankylosing Spondylitis
Innflammatory disorder affecting primarily Axial Skeleton & Peripheral Joints
Clinical features
 20 – 30 years age
 Men > women
 Chronic lower back pain
 Spine fracture
 Morning stiffness (improves with exercise)
 Extraarticular manifestations
o Anterior uveitis
o Aortic insufficiency  leading to CHF & third-degree heart block
Examination
 Schober test  Decreased lumbar spine mobility
 Obliteration of Lumbar Lordosis
X-ray
 Sacroiliitis
 Chronic spine inflammation  bamboo spine & squaring of vertebral bodies
Diagnosis  based on clinical & x-ray findings.
Treatment
 NSAIDs
 Physical therapy
 TNF blockers (infliximab, adalimumab, etanercept)
Reactive Arthritis
Complication from an infection somewhere in the body
Two types of syndromes following Infection
 Reiter syndrome
o Etiology  Non-gonococcal urethritis (chlamydia, ureaplasma)
o Clinical presentation
 Triad
 Conjunctivitis
 Arthritis
 Urethritis
 Mucocutaneous manifestations
 Keratoderma Blennorrhagica
 Circinate balanitis
 Oral or Genital ulcers
 ReA after an Infectious diarrhea caused by Campylobacter, Shigella, Salmonella
o Clinical Features
 Monoarthritis of a knee
 Inflammatory arthritis of IP joints.
 Heel Pain, Achilles tendinitis / Plantar Fasciitis
 Macules, Vesicles & Pustules on hands & feet
Investigations
 Rheumatoid factor & ANA are negative
 HLA-B27 positive
 Raised ESR
Treatment
 Rest
 Analgesics
 Nonspecific urethritis -> tetracycline
 Sulfasalazine or methotrexate
 Glucocorticoid therapy -> prevent rapid joint destruction.
Psoriatic Arthritis
Clinical features
o Peripheral arthritis Involving DIP joints
o Sacroiliitis/spondylitis
o Psoriatic nail disease (pitting & transverse ridges in nails)  sausage-shaped digit
o Scaly skin lesions are seen over extensor surfaces
Investigations
 Raised ESR
 RF & ANA are negative
 X-ray → Periarticular Osteoporosis
Treatment
 Analgesics
 Hydroxy Chloroquine, Methotrexate, Leflunomide
 Retinoid etretinate 30 mg/day is effective for both arthritis & skin lesions
 Photochemotherapy with Long Wave Ultraviolet Light (PUVA) -> severe skin lesions

Enteropathic Arthropathy
Occurs with UC & Crohn’s disease
Clinical features
o Pyoderma gangrenosum
o Erythema nodosum.
o Arthritic Flares
Q. ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES
Antibodies directed against certain proteins in the cytoplasm of neutrophils.
o Cytoplasmic (C) ANCA
o Diffuse staining pattern.
o Seen in Wegener granulomatosis.
o Perinuclear (P) ANCA
o Localized staining pattern
o Directed against enzyme myeloperoxidase
o Seen in
 PAN
 Churg-Strauss Syndrome

Q. ALKALINE PHOSPHATASE
Derived from three sources
1. Hepatobiliary system
2. Bone
3. Intestinal tract
Elevated ALP
 Extrahepatic & Intrahepatic biliary obstruction
 Drug induced cholestasis
 Primary biliary cirrhosis
 Liver abscess
 Sclerosing cholangitis
 Alcoholic hepatitis
 Primary & secondaries of liver
 Hodgkin’s disease
 Non-Hodgkin’s lymphoma
 CCF
 Hyperthyroidism
 Diabetes mellitus
 Bone disease (Paget’s disease, Osteomalacia)
 Pregnancy
 Miliary tuberculosis
 CMV infection
Q. OSTEOARTHRITIS (OA)
Degenerative disease characterized by Articular cartilage deterioration with new bone formation at articular surface
Examination
o Tenderness on joint line
o Crepitus on Moving Joint
o Irregular & enlarged-looking joint due to formation of peripheral osteophytes
o Deformity – Varus of knee, Flexion-Adduction-External Rotation of hip
o Effusion
o Terminal limitation of joint movement
Investigations
o X ray
o Narrowing of joint space
o Subchondral sclerosis
o Subchondral cysts
o Osteophyte formation
o Loose bodies
o Deformity of the joint
Treatment
 Analgesics
 Chondroprotective agents → Glucosamine & Chondroitin sulphate
 Viscosuplementation → Sodium Hylarunon
 Supportive therapy
 Weight reduction
 Exercises
 Hot fomentation
 Surgical
o Osteotomy
o Joint replacement
o Joint debridement
Q. GOUT
Disturbed purine metabolism leading to excessive accumulation or impaired excretion of uric acid
Tissues of predilection are → cartilage, tendon, bursa Patient
Clinical features
 40 years of age
 Arthritis – MC in MP joint of big toe
 Bursitis – MC olecranon bursa
 Tophi formation -→ deposit of uric acid salt in soft tissue
Confirmation of diagnosis
 Urate crystals in aspirate from a joint or bursa
 High serum uric acid levels
Treatment
 NSAIDs
 Uricosuric drugs
 Uric acid inhibitors

Q. PSEUDOGOUT
CPPD → calcium pyrophosphate dihydrate crystal deposition in joints
Clinical features
 Hyperparathyroidism
 Hemochromatosis
 Hypophosphatemia
 Hypomagnesemia
Clinical Presentation.
 Possible acute presentation like gout involving
o Knees
o Wrist
o Shoulder
o Ankle
Diagnosis
 Synovial fluid evaluation → Rectangular, Rhomboid, Positive Birefringent Crystals
 X-ray → Linear Radio-dense deposits in Joint Menisci or Articular Cartilage (Chondrocalcinosis).
Treatment.
 Low doses of Colchicine
 NSAID
 Intra-articular Corticosteroids
Q. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Multisystem connective tissue disease of unknow etiology in which tissues & cells are damaged by Autoantibodies
MC in women of child bearing age
Etiopathogenesis
 Disturbance of immune regulation.
 Genetic Predilection (HLA-B8 and DR3)
 Environmental factors (sunlight)
 Drugs
o Estrogens, oral contraceptives
o Quinidine
o INH
o Hydralazine
o Chlorpromazine
o Phenytoin
o Procainamide (most frequent)
 Infection  EB virus.
Autoantibodies in SLE
Antinuclear antibodies Anti-cardiolipin
 Anti-DNA (single strand) Anti-erythrocyte
 Anti-DNA (double strand) Anti-lymphocyte
 Anti-RNA Anti-platelet
 Anti-Sm Anti-neuronal
 Anti-UI-RNP Anti-MA
 Anti-Ro/SS-A Anti-PCNA
 Anti-La/SS-B

Clinical Presentation. (4 of following diagnostic criteria required for a diagnosis of SLE)

1. Malar rash  Butterfly rash flare with exposure to UV-B light (photosensitive)
2. Discoid rash  circular rash with a raised rim occurring over scalp & face
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis (pleuritis or pericarditis)
7. Libman-Sacks endocarditis
8. Renal involvement
9. Neurologic disorder (seizures or psychosis)
10. Hematologic disorder (Hemolytic Anemia, Leukopenia, Thrombocytopenia)
11. Immunologic markers (anti-dsDNA, anti-SM, & other ANAs)
Diagnosis.
• ANA antibody assay
• C3, C4 levels decreased
• Elevated ESR.
• ELISA  Lupus anticoagulants (anticardiolipin antibody)
o Prolonged PTT, not correctable by the addition of normal plasma
o Responsible for Recurrent 1st Trimester Abortions & Thrombocytopenia
Treatment.
• NSAIDs
• Corticosteroid creams  skin rash
• Hydroxychloroquine & Oral Corticosteroids  Skin & arthritic symptoms.
• Cytotoxic drugs (Azathioprine, Cyclophosphamide)  severe symptoms
• Mycophenolate  Lupus Nephritis

Q. SCLERODERMA
Systemic sclerosis is a chronic multisystem disease characterized by Fibrosis of Skin, Blood vessels, Viseral Organs
Clinical Presentation.
 Skin thickening
 Raynaud phenomenon (due to vascular damage & diminished blood flow to the extremities)
 GI
o Esophageal dysmotility
o Hypomotility of small intestine with Bacterial Overgrowth & Malabsorption
o Dilatation of large intestine with formation of large diverticula
 Pulmonary
o Pulmonary fibrosis with Restrictive lung disease & Cor pulmonale
• Renal
o Scleroderma renal crisis → malignant hypertension develops → causes acute renal failure
• Lungs
o Diffuse Interstitial Fibrosis
• CREST syndrome / limited scleroderma / limited cutaneous systemic sclerosis.
o Calcinosis (calcium deposits in soft tissues, usually fingers (especially PIP joints), knees, & elbows)
o Raynaud’s phenomenon
o Esophageal dysfunction
o Sclerodactyly (skin thickening, primarily affecting fingers & toes)
o Telangiectasias
Investigations
 Elevated ESR
 Antinuclear antibodies [anti-topoisomerase 1 & anti-centromere]
 CXR, CT thorax
 Pulmonary function test
 ECG → Cardiac involvement & Pulmonary HTN
 Barium swallow test
Treatment.
 No Specific cure
 Skin manifestations → D-penicillamine.
 Raynaud phenomenon → CCB specifically nifedipine.
 Hypertension & Renal crisis → ACE inhibitors
Q. SJÖGREN SYNDROME
Chronic Multi-system autoimmune disease characterized by lymphocytic infiltration of exocrine glands, resulting in
 Xerostomia
 Dry eyes
Types
 Primary / Sicca syndrome
 Secondary
o RA
o Primary biliary cirrhosis
o SLE.
Clinical Presentation
Glandular Extra-Glandular
Dry eyes Arthritis
Dry Mouth Raynaud’s phenomenon
Parotid gland enlargement Vasculitis
Lymphoma
Renal tubular acidosis
Examination
 Schirmer’s test → decreased tear production
 Rose Bengal stain → corneal ulcerations
 ANA → positive [anti-Ro (SSA) & anti-La (SSB)]
 Measurement of salivary flow is done by salivary Sialometry.
 Salivary gland involvement may be tested by salivary Scintigraphy.
 Salivary glands biopsy → Lymphocytic infiltration
Treatment.
 Artificial tears
 Pilocarpine & Cevimeline → increase acetylcholine → increase tear & saliva production
 Immunosuppressive therapy (cyclosporin A, azathioprine, methotrexate and mycophenolic acid)

Q. OSTEOMALACIA Etiology
 Dietary deficiency of vitamin D
 Under-nutrition during pregnancy
 Mal-absorption syndrome
 After partial gastrectomy
Clinical features
 Bone pains
 Spontaneous #
Radiological examination
 Looser's zone (pseudo #) → radiolucent zones occurring at sites of stress
 Protrusio-acetabuli → acetabulum protruding into the pelvis
Treatment
 Medical treatment
o Loading dose → vitamin D 6,00,000 units
o Maintenance dose → 400 I.U vitamin D / day
 Corrective osteotomy
Q. INFLAMMATORY MYOPATHIES
Condition of unknown etiology
Skeletal muscle is damaged by a nonsuppurative inflammatory process due to lymphocytic infiltration
Includes
 Polymyositis
 Dermatomyositis
 Inclusion body myositis
Classification
 Group 1 → Idiopathic polymyositis
 Group 2 → Idiopathic dermatomyositis
 Group 3 → Dermatomyositis (polymyositis) associated with Neoplasia
 Group 4 → Childhood dermatomyositis associated with Vasculitis
 Group 5 → Polymyositis with Collagen Vascular Disease
Clinical features
 Progressive muscle weakness
 Ocular muscles are never involved (differentiates from myasthenia gravis & Eaton-Lambert syndrome)
 Maculopapular eruption
 Heliotrope rash → purple discoloration of face, eyelids & sun-exposed areas
 Itching an& d periorbital oedema
 Subcutaneous calcification
 Gottron’s papules → scaly lesions over knuckles
 V sign → Erythematous rash over the anterior chest
 Shawl sign → Erythematous rash over back & shoulders
 Extra-muscular Manifestations
o Systemic symptoms
 Fever
 Malaise
 Arthralgia
 Raynaud’s phenomenon.
o GI symptoms
 Dysphagia
 GI ulcerations.
o Cardiac symptoms
 A-V conduction defects
 Tachyarrhythmias
 Dilated cardiomyopathy
 Congestive cardiac failure
o Pulmonary symptoms
 Interstitia lung disease
 Thoracic myopathy
Investigations
 Serum enzymes (CK, aldolase, AST, LDH & ALT) → increased
 ESR → Raised
 EMG → markedly increased insertional activity (muscle irritability)
 Muscle biopsy → Inflammatory Cell Infiltrates (hallmark of polymyositis)
Treatment
 Step 1 → Oral prednisolone 1 mg/kg/day
 Step 2 → Immunosuppressive drugs [Azathioprine, Methotrexate]
 Step 3 → IVIG
 Step 4 → Cyclophosphamide, Chlorambucil, Mycophenolate Mofetil

Q. OSTEOPOROSIS
Reduction in bone density due to decrease in bone mass.
Cause

Clinical features
 Pain
 Pathological #
o Dorso-lumbar spine
o Colles #
o # of neck of femur
X-ray
 Loss of vertical height of a vertebra due to collapse.
 Cod fish appearance → disc bulges into adjacent vertebral bodies [disc becomes biconvex]
 Ground glass appearance of bones
 Metacarpal index, Vertebral index, Singh's index [quantification of osteoporosis]
Investigations
 Biochemistry → Serum calcium, phosphates & ALP are within normal limits
 Neutron activation analysis
 Bone biopsy
Treatment
 Calcium supplementation
 Vitamin D
 Alandronate
 Calcitonin
 Tiparatide [recombinant human PTH] → Anabolic agent increasing osteoblastic new bone formation
Q. POLYARTERITIS NODOSA POLYARTERITIS NODOSA (PAN)
Necrotizing inflammation of small & medium sized muscular arteries
Thrombosis & infarction of tissues supplied by involved vessels
Aneurysmal dilatation along involved arteries are characteristic of PAN
Pulmonary Arteries are Characteristically not Involved
Mechanisms of Blood Vessel Damage
 Immunopathogenic
o Immune complex formation in situ
o Antibody mediated cell damage (endothelium & blood vessel tissue)
o Cytotoxic-T cells against components of blood vessel
 Nonimmune mechanisms
o Infiltration of vessel wall by microbial agents
Clinical features

Diagnosis
 Elevated ESR
 Hyper-gammaglobulinaemia
 Biopsy of involved organs → pathologic changes in medium-size arteries.
 Angiogram of abdominal vessels → aneurysms affecting arteries of kidneys & GI tract
Treatment
 Corticosteroids → Prednisone 1 mg/kg/day
 Immunosuppressive drugs (cyclophosphamide → 2 mg/kg/day)

Q. FELTY’S SYNDROME
Variants of Rheumatoid Arthritis
Characterized by
 Pancytopenia
 Neutropenia
 Splenomegaly
 Lymphadenopathy
Q. STILL’S DISEASE (rheumatoid arthritis occurring in children)
Variants of Rheumatoid Arthritis
Characterized
 Mono or Polyarthritis
 Fever
 Maculopapular rash
 Hepatosplenomegaly
 Lymphadenopathy
 Leukocytosis
 Negative → RA factor & ANA are negative

NEPHROLOGY
Q. HEMATURIA
Types
 Glomerular hematuria
o Dysmorphic RBC
o MCV < 72 fl
o Presence of RBC casts
o Concomitant proteinuria (> 1 gm/day)
 Non-glomerular hematuria
o Isomorphic RBC
o MCV > 72 fl
o Absence of RBC casts
o No significant proteinuria
Causes
Renal Extra-Renal Systemic
Glomerular disease Calculi Coagulation disorders
Carcinoma Infection Anticoagulant therapy
Cystic disease Neoplasm Sickle cell disease
Trauma Prostatitis Vasculitis.
Vascular malformation Urethritis
Emboli Bladder-catheterization

Intermittent hematuria
 IgA nephropathy
 Alport syndrome
 Tumor
 ADPKD

Differential Diagnosis
 Porphyria Melanoma Alkaptonuria.
 Hemoglobinuria
 Myoglobinuria
 Drugs (Rifampicin)
 Beetroot ingestion
Q. ACUTE NEPHRITIC SYNDROME / GLOMERULONEPHRITIS
Glomerular inflammation leading to immunologically-mediated injury to glomeruli
Etiology
Primary Secondary
IgA nephropathy SLE
RPGN HSP
PSGN
MPGN
Goodpasture's syndrome
Microscopic polyangiitis
Wegener's granulomatosis
Sickle cell nephropathy
Pathogenesis
 Deposition of immune complexes in glomeruli which triggers
o Complement activation
o Fibrin deposition
o Platelet aggregation
o Release of cytokines & free oxygen radicals
Clinical Features
 Haematuria
 RBC casts
 Oliguria
 Hypertension
 Uremia
 Proteinuria < 3.5 g/day
 Oedema
Investigations
 Urine microscopy → RBC casts, dysmorphic red cells
 Cultures → Throat swab, Inflamed skin swab
 Antistreptolysin-0 (ASO) titer
 C3 level (complement) → Reduced
 Urinary protein
 Urea and creatinine → Elevated
 Renal biopsy
o Electron Microscopic → proliferation of glomerular cells & infiltration by leukocytes.
o Immunofluorescence Microscopy → Immune Complex deposition
Management
 Rest
 Salt restriction
 Antihypertensives
 Antibiotics
 Dialysis → severe oliguria, fluid overload & hyperkalemia
Q. NEPHROTIC SYNDROME
Presence of GN sufficient to produce
 Proteinuria >3.5 g/day
 Hyperlipidemia
 Edema
 Hypoalbuminemia
Etiology
Primary Secondary
Minimal change disease DM
MGN Amyloidosis
FSGS Drugs
MPGN  Gold
 Penicillamine
 Probenecid
 Captopril
 NSAIDs
Infections
 Bacterial endocarditis
 Hepatitis B
 Syphilis
 Malaria
Malignancy
 Hodgkin’s lymphoma
 Leukemia
 Ca Breast & GI tract
Clinical Features
 Insidious onset of generalised oedema
 Frothy urine due to presence of protein
Complications
 Venous & pulmonary embolism (urinary loss of antithrombin III, increased clotting factors 2, 5. 7. 8, 10]
 Loss of Immunoglobulins in urine → Infections (pneumococcal peritonitis)
 Compensatory Hypercholesterolemia in response to Hypoalbuminemia (atherosclerosis, xanthomata)
 Loss of specific binding proteins, e.g., transferrin, thyroid-binding globulin
Investigation
 Urine protein → > 3.5 g/day
 Serum Albumin
 Serum BUN, Creatinine
 Renal Biopsy
Treatment
 Bed-rest
 GFR > 60 ml/min → no dietary protein restriction required.
 GFR < 60 ml/min → dietary protein restriction of 0.8 gm/kg/day
 Diuretics → relieve oedema but do not treat the underlying disorder
 Salt-free albumin infusion
 Treatment of the underlying cause or precipitating factor
 Proteinuria → controlled by ACE inhibitors.
 Anticoagulation → deep vein thrombosis, arterial thrombosis & pulmonary oedema
Q. POLYCYSTIC KIDNEY DISEASE
Two modes of inheritance
 Autosomal recessive → Mutation in PKHD1 (Polycystic kidney & hepatic disease) gene on chromosome 6
 Autosomal dominant → Mutation in → PKD1 gene on chromosome 16, PKD2 gene on chromosome 4
Clinical Features
 Flank pain
 Acute loin pain or Renal colic due to haemorrhage into cysts.
 Nocturia
 Hematuria
 Urinary infection
 Uremia
 Associated with
o Hepatic cysts
o Intracranial aneurysms
Complications
 UTI
 Hypertension
 Renal Calculi
Diagnosis
 Renal ultrasound or CT → Multiple cysts
 Liver US
 Head CT → Intracranial aneurysms
Treatment
 Management of complications (UTI, calculi & hypertension)
 Dialysis if renal function declines.
 Nephrectomy for intractable pain

Q. ACUTE KIDNEY INJURY/ACUTE RENAL FAILURE (ARF)

Syndrome characterized by
 Rapid decline in GFR (hours to days)
 Retention of nitrogenous waste products,
 Electrolyte & Acid-Base disturbances
RIFLE Criteria for Acute Kidney Injury
Category GFR criteria
Risk GFR reduction > 25%
Injury GFR reduction > 50%
Failure GFR reduction > 75%
Loss Persistent AKI > 4 weeks
ESRD ESRD > 3 months
Causes
Pre-renal failure Intrarenal failure Postrenal failure
Loss of fluid Acute tubular necrosis Crystals
 Vomiting Rhabdomyolysis Calculi
 Diarrhea Drugs (aminoglycosides, NSAIDs) Papillary necrosis
 Burns Contrast dye Prostate enlargement
 Hemorrhage Glomerulonephritis Pelvic neoplasm
 Diuretics Vasculitis Bladder neoplasm
Redistribution of fluid Interstitial nephritis Retroperitoneal neoplasm
 Hepatic disease Urethral obstruction
 Nephritic syndrome Bladder neck obstruction
 Peritonitis
 Malnutrition
Decreased cardiac output
 Cardiogenic shock
 MI
 Myocarditis
 Arrhythmias
 Pulmonary emboli
 Cardiac tamponade
Vasodilation
 Hypotension
 Sepsis
 Anaphylactic shock
 Hypoxemia
 ACE inhibitors
Renal vasoconstriction
 Hepato-renal syndrome,
 Pg synthesis inhibition
Management
 Treatment of Etiology
 Conservative therapy
o Urinary catheter
o Limit fluids to 500 ml + Previous day’s losses
o Avoid nephrotoxic drugs
o Treat hyperkaliemia & Acidosis
 Dialysis for
o Volume overload
o Uraemia
o Hyperkalaemic acidosis
o Uremic pericarditis
o Serum creatinine > 8 mg/dl
 Alkalinisation of urine [NaHCO3 → for Rhabdomyolysis
 Rasburicase → Tumor lysis syndrome
 Prednisone → Hastens recovery from drug induced Acute Interstitial Nephritis
Q. CHRONIC KIDNEY FAILURE
Several etiologies lasting for > 3 months leading to reduction in nephron function leading to ESRD
Causes
 Diabetic nephropathy
 Hypertension
 Chronic glomerulonephritis
 Polycystic kidney disease
 Chronic pyelonephritis
 Interstitial nephritis
 Vesico-ureteric reflux
 Nephrocalcinosis
Manifestations.

Investigations
 Urine analysis
 Blood biochemistry
 Ultrasonography to assess the size of kidneys.
o In CRF, both kidneys are small & contracted (< 8 cm length is taken as contracted kidney).
o Normal size of kidney corresponds to 3 times length of L1 vertebra
o CRF with enlarged kidneys
 Diabetes mellitus with CRF
 Polycystic kidney disease
 Amyloid kidney
 Bilateral obstruction (hydronephrosis)
 Myeloma kidney
 HIV
Management
 HTN Control  ACE inhibitors
 Protein restriction to 40 g/day
 Avoidance of high potassium foods.
 Salt restriction
 Hypocalcaemia  Calcitriol, Vitamin D
 Treatment of Hyperphosphataemia  Phosphate binders (Aluminum hydroxide, Calcium carbonate)
 Treatment of Hyperparathyroidism  Calcium carbonate, Vitamin D
 Dialysis indications
o Severe Hyperkalaemia
o Pulmonary oedema or Severe Fluid Overload
o Severe Metabolic Acidosis
o Uremic Pericarditis
o Uremic Encephalopathy
• Kidney transplantation

Q. GOODPASTURE SYNDROME
Investigations
 Urine microscopy → RBC casts
 C3 level (complement) → Reduced
 Urinary protein
 Urea and creatinine → Elevated
 Renal biopsy Immunofluorescence  Anti-glomerular basement membrane (GBM) antibody
Treatment
 Rest
 Salt restriction
 Antihypertensives
 Antibiotics
 Dialysis → severe oliguria, fluid overload & hyperkalemi
 Plasmapheresis
 Glucocorticoids
 Cyclophosphamide, Azathioprine

Q. HAEMODIALYSIS (HD)
Fluid & substances of Blood are exchanged via a concentration gradient across a semipermeable membrane
Indications
 ARF
 Toxins
 Drugs
 CRF patients awaiting renal transplantation
 Patients with CRF in whom quality of life has deteriorated.
Access
 Subcutaneous AV fistula or Shunt.
 Prosthetic fistulas
 Percutaneous subclavian
 Femoral Catheters.
Complications
 Complications Arising due to Access
o Infection
o Thrombosis
o Vascular compromise
o High output CCF.
 Complications Arising due to Dialysis Procedure
o Haemorrhage, Hypotension
o Cardiac ischaemia
o Hypoventilation, Hypoxaemia
o Anticoagulation leading to bleeding diathesis
o Air embolism
 Long term complications
o Aggravation of Anaemia by Blood Loss & Folate Deficiency
o Pericarditis, Diverticulosis, Hepatitis (non-A, non-B)
o Aluminium intoxication  Dialysis Dementia, dyspraxia, Seizures.
Q. RENAL REPLACEMENT THERAPIES
Dialysis  Clearance of small molecules & toxins using diffusion across a membrane
 Haemodialysis  Dialysis with clearance across a synthetic membrane
 Peritoneal dialysis  Dialysis with clearance across a native membrane
Ultrafiltration  Fluid removal across a Semi-permeable membrane under pressure
Haemofiltration  Continuous Removal of Large amounts of solutes with Concurrent Electrolyte Solution Reinfusion
Haemo-diafiltration  Combination of haemodialysis & haemofiltration
Continuous Renal Replacement Therapy

URINARY TRACT INFECTION

Upper urinary tract infection → Infection involving kidney.
Lower urinary tract infection → Infection involving bladder, prostate & urethra
Bacteriuria → he presence of bacteria in urine
Significant bacteriuria → presence of >1,00,000 (105) CFU of bacteria per milliliter of midstream urine
Pyelonephritis → inflammation of the renal parenchyma
Acute bacterial pyelonephritis → clinical syndrome characterized by
 Chills & fever
 Flank pain
 Constitutional symptoms caused by bacterial invasion of kidney.
Chronic pyelonephritis → renal disease that is caused by a variety of disorders such as
 Chronic obstructive uropathy
 Vesicoureteral reflux (VUR)
 Renal medullary disease
 Drugs & toxins
 Chronic bacteriuria
Cystitis → infection confined to urinary bladder.
Urethritis → infection confined to urethra.
Prostatitis → infection confined to prostate
Relapse → recurring infection due to same micro-organism that is often drug resistant.
Reinfection → recurring infection due to a different micro-organism that is usually drug susceptible.
Asymptomatic bacteriuria → presence of bacteriuria, in absence of symptoms.
Uncomplicated urinary infection →
 Episode of cysto-urethritis following bacterial colonization of urethral & bladder mucosa.
 Sequelae are rare.
Complicated urinary infection
 Infections involving parenchyma (pyelonephritis or prostatitis)
 Episodes may be refractory to therapy, often resulting in relapses
 Occasionally leading to significant sequelae such as Sepsis, Metastatic Abscesses, ARF
Risk Factors of Urinary Tract Infection
 Obstruction to urine flow
o Congenital anomalies
o Renal calculi
o Ureteral occlusion
 Vesicoureteral reflux
 Residual urine in bladder
o Neurogenic bladder
o Urethral stricture
o Prostatic hypertrophy
 Instrumentation of urinary tract
o Indwelling urinary catheter
o Catheterization
o Urethral dilation
o Cystoscopy
Common microbial pathogens causing UTI
 Escherichia coli
 Klebsiella
 Enterobacter
 Proteus
 Morganella
 Providencia
 Pseudomonas aeruginosa
 Staphylococcus saprophyticus
 Staphylococcus aureus
 Candida albicans
Symptoms of UTI
 Frequency
 Dysuria
 Hematuria
 Incontinence
 Retention of urine
 Fever with chills & rigors
 Pain over loin or Suprapubic region
Investigations
 Urine specimens for culture, sensitivity & CFU counts.
 Localization of infection with segmented cultures of lower urinary tract in men
o Positive culture from first 10 ml of voided urine → urethral infection
o Positive culture from midstream sample of urine → bladder infection
o Positive culture from first 10 ml of voided urine after a prostatic massage → prostatic infection
 Gram Staining & Microscopic visualization of urine sample
 Radiography
o VUR
o Renal calculi
o Obstructing mass
Treatment
 Uncomplicated UTI [oral therapy]
o Trimethoprim-sulfamethoxazole every 12 hours.
o Ciprofloxacin 250–500 mg every 12 hours
o Ampicillin 500 mg every 6 hours
o Tetracycline 250–500 mg every 6 hours
 Prostatic infection [therapy for 10 – 14 days]
o Trimethoprim-sulfamethoxazole BID
o Ciprofloxacin 250–500 mg BID
o Ampicillin 500 mg BID
 Complicated UTI [parenteral therapy]
o Gentamicin 2 mg/kg/day every 8 hours.
o Tobramycin 2 mg/kg/day every 8 hours
o Ampicillin 1 gm every 4 hours

Q. ACUTE BACTERIAL PYELONEPHRITIS

Acute pyogenic infection of kidney
Women > men [due to Short urethra & Proximity of anus]
Route of infection
 Ascending Infection → ascension from urethral meatus.
 Descending infection → Hematogenous

Predisposing factors
 Obstruction to urine flow
o Congenital anomalies
o Renal calculi
o Ureteral occlusion
 Vesicoureteral reflux
 Residual urine in bladder
o Neurogenic bladder
o Urethral stricture
o Prostatic hypertrophy
 Instrumentation of urinary tract
o Indwelling urinary catheter
o Catheterization
o Urethral dilation
o Cystoscopy

Causative agents
 Escherichia coli
 Klebsiella Enterobacter Proteus Morganella Providencia
 Pseudomonas aeruginosa
 Staphylococcus saprophyticus
 Staphylococcus aureus
 Candida albicans
Clinical features
 Chills
 Fever
 Flank pain
 Nausea & Vomiting
 Costovertebral angle tenderness
 Increased frequency in urination
 Dysuria
Investigations
 Urine specimens for culture, sensitivity & CFU counts [Significant bacteriuria]
 U/S or CT → Obstruction, Renal or Perinephric abscess
Treatment → Antibiotics for 10–14 days
 Fluoroquinolone
 Ampicillin
 Gentamicin
 Third-generation cephalosporin
 Do not use nitrofurantoin → effectiveness has been proven only in lower urinary tract.

Q. MICROALBUMINURIA
Excretion of albumin of 20–200 micro-gram per minute (albumin excretion rate or AER), or
Daily excretion of albumin in range of 30–300 mg.
Causes
 Diabetes mellitus with early renal involvement
 Hypertension
 Myocardial infarction
 Acute phase response
 Obesity
 Hyperlipidemia
 Alcohol intake
 Physical exercise

Proteinuria values
 Normal range < 30 mg/24 hours
 Microalbuminuria 30–300 mg/24 hours
 Macroalbuminuria > 300 mg/24 hours
Q. PROTEINURIA
Urine protein composition
 Tomm-Horsfall protein
 Blood group related antigen
 Albumin
 Mucopolysaccharide
 Immunoglobulins
 hormones & enzymes
Classification of Proteinuria
GLOMERULAR PROTEINURIA TUBULAR PROTEINURIA
 Injury to glomerulus Injury to Tubules
 Predominantly of albuminuria > 3.5 g/day  Failure to reabsorb proteins filtered by Glomerulus
Primary glomerular disorders  Release of Tomm-Horsfall protein
 Minimal change Causes
 MPGN Hereditary
 FSGS  Polycystic kidney disesase
 MGN  Medullary cystic disease
 RPGN Infections
Hereditary  Pyelonephritis
 Alport’s syndrome  Tuberculosis
 Fabry’s disease Metabolic
Infections  Diabetes mellitus
 Bacterial endocarditis  Hyperuricaemia
 PSGN  Uricosuria
 Secondary syphilis  Hypercalciuria
 Hepatitis B & C  Oxalosis
 HIV  Cystinosis
 Malaria Immunologic
Immunologic  Sjögren’s syndrome
 SLE  Renal transplant rejection
 Sjögren’s syndrome  Drug hypersensitivity
 Henoch-Schönlein purpura  Sarcoidosis
 Wegener’s granulomatosis Toxic injury
 Goodpasture’s syndrome  Drugs
Drugs → Penicillamine, Lithium, NSAIDs, ACEI  Radiations
 Poisons
OVERFLOW PROTEINURIA OTHER TYPES OF PROTEINURIA
Filtration by normal glomerulus of large amount of Benign orthostatic proteinuria [adolescents]
small molecular-weight protein  Proteinuria should not exceed 1 gm per day
 Multiple myeloma Transient proteinuria
 Hemoglobinuria  Associated with conditions like
 Rhabdomyolysis o Cardiac failure
o Fever
o Heavy exercise
Q. Renovascular hypertension
Systemic HTN that manifests secondary to compromised blood supply to kidneys
Etiology
 Renal artery stenosis (RAS), mostly secondary to atherosclerosis
 Fibromuscular dysplasia (FMD)
 Arteritis such as Takayasu’s, APLA, or mid aortic syndrome
 Extrinsic compression of a renal artery
 Renal artery dissection or infarction
 Radiation fibrosis

Pathogenesis
Decreased perfusion to the kidney → Activation of RAAS pathway

Angiotensin 2 → Vasoconstriction
Secretion of aldosterone → sodium &water retention → raising blood pressure.
Increased synthesis of collagen type I & III → thickening of the vascular wall & myocardium
Clinical features
 Resistant hypertension → Uncontrolled BP requiring use of > 2 antihypertensive, one of which is a diuretic
 Raised BUN & Creatinine
Investigations
 BMP
 CMP
 Urine analysis
 Plasma renin-aldosterone ratio
 CT angiography
 US kidney
Treatment
 Anti-HTH
 Percutaneous angioplasty is the treatment of choice
Differential diagnosis
 Pheochromocytoma
 Primary Hyperaldosteronism
 Obstructive Sleep Apnea
 Coarctation of aorta

Complications
 Renal failure
 Myocardial infarction
 Stroke
 Pulmonary edema
 Retinopathy
 Congestive heart failure
Q. RENAL OSTEODYSTROPHY (OSTEITIS FIBROSA CYSTICA).
CRF → chronic hypocalcemia → secondary hyperparathyroidism → calcium resorption from bones
Clinical features
 Bone pain
 Fractures
 Osteomalacia
 Osteosclerosis
Treatment
 Improving calcium & phosphorous levels
 Cinacalcet (oral calcimimetic agent  increases sensitivity of calcium-sensing receptors)
 Parathyroidectomy (Severe hyperparathyroidism that does not respond to medications)

Q. NEPHROLITHIASIS
Predisposing factors
 Volume depletion
 Lack of stone-inhibiting proteins in urine (osteopontin, nephrocalcin.)
 Hereditary predisposition to stone
 Errors of metabolism (gout, cystinuria, primary hyperoxaluria)
 Infection → Urea-splitting Streptococci, Staphylococci, Proteus
 Decreased urinary citrate [Binds to Calcium prevents Stone formation]
 Urine pH
o Acidic → Cystine, Uric acid
o Alkaline → Struvite, Calcium
Types of stones
 Calcium oxalate & calcium phosphate
 Struvite/Triple stones (Mg/aluminum/phosphate)
 Uric acid
 Cystine
 Indinavir
HEMATOLOGY
ANEMIA
 Anemia is a condition marked by the following
o Hematocrit
 <41% in men
 <36% in women
o Hemoglobin
 <13.5 g/dL in men
 <12 g/dL in women
Etiological classification of anemia.
Blood Loss Impaired Red Cell Production Hemolysis
Trauma Nutritional deficiencies Intrinsic
Lesions of GIT  Iron  Hereditary spherocytosis
Gynecological disorders  B12  Hereditary elliptocytosis
 B9  G6PD deficiency
 Vitamin C  PNH
Genetic defects  Pyruvate kinase deficiency
 Thalassemia  Thalassemia
 Fanconi anemia  SCD
Erythropoietin deficiency [CRF] Extrinsic
Aplastic anemia Antibody-mediated destruction
Anemia of chronic disease  Erythroblastosis fetalis
Hematopoietic neoplasm  Transfusion reactions
 ALL  Drug-associated
 MDS  SLE
 MPD Microangiopathic Hemolysis
Parvovirus B19 infection  Hemolytic uremic syndrome
 DIC
 TTP
Infection
 Malaria
 Babesiosis
Hypersplenism
Defective Cardiac valves
Q. IRON DEFICIENCY ANEMIA
Causes of Iron Deficiency
Increased iron demand Physiologic iron loss Pathologic iron loss Decreased iron intake
Postnatal growth spurt Menstruation Gastrointestinal bleeding Cereal rich diet
Adolescent growth spurt Pregnancy Genitourinary bleeding Pica
Erythropoietin therapy Pulmonary haemosiderosis Malabsorption
Pregnancy Intravascular haemolysis
Iron requirements
• Males 1 mg / day
• Females 2 mg / day
• Pregnancy 3 mg / day
Stages in Iron Deficiency Anaemia
• Negative iron balance
• Iron deficient erythropoiesis
• Iron deficiency anaemia.

Clinical features
• Fatigue, Poor exercise tolerance
• Pallor
• Dyspnea
• Syncope
• Tachycardia, Palpitations
• Systolic ejection murmur (“flow” murmur)
• Brittle nails
• Koilonychia  Spoon-shaped nails
• Glossitis, Somatitis
• Pica  Persistent Involuntary Craving for Non-food substances
o Hair (trichophagia)
o Faeces (coprophagia)
o Ice (pagophagia)
o Soil (geophagia)
• Plummer-Vinson syndrome (postcricoid web)
• Menorrhagia
Investigations
Management
• Vitamin C supplementation → Increased Iron absorption
• Iron Requirement
o Total dose = Hb deficit (gm/dL) × lean body weight (lb) + 1000 (mg of iron needed for storage).
o 2 ml of Iron Dextran contains 100 mg of iron.

Practical Classification of Anaemia

Microcytic (MCV < 80 fL) Macrocytic (MCV > 100 fL) Normocytic (MCV 80–100 fL)
IDA B12/B9 deficiency Intrinsic causes
Thalassaemia Myelodysplastic syndrome • Aplastic anaemia
Sideroblastic anaemia Liver disease • PNH
Lead poisoning Reticulocytosis • MDS
Rheumatoid arthritis Hydroxyurea treatment • Congenital Dys-erythropoiesis
Hodgkin’s lymphoma Excess alcohol intake Extrinsic causes
Myelofibrosis • Erythropoitin insufficiency
• Anaemia of chronic disease
• Marrow infiltrative disorders
• Haemolytic anaemias
• Drug associated
• Toxin associated
• Radiation associated

Q. DIFFERENTIAL DIAGNOSIS OF GENERALIZED LYMPHADENOPATHY

 Lymphomas (Hodgkin's, non-Hodgkin's)
 Leukaemias (ALL, CLL, CML in blast crisis)
 Disseminated tuberculosis
 HIV
 Secondary syphilis
 Infectious mononucleosis
 Brucellosis
 Systemic lupus erythematosus
 Rheumatoid arthritis
 Metastatic disease
 Local infections (Cellulitis, Pharyngitis)
Q. BLOOD TRANSFUSION
Indications
 Blood loss in RTA.
 Blood loss in surgery.
 Severe anemia
o Iron deficiency
o Thalassaemia
o Aplastic anaemia
o Anaemia of chronic disease
o Connective tissue disorders
o Malignancy
 Bleeding disorders
 Extensive burns
One unit of RBCs increases Hb by 1g/dL
Blood components

Complications of blood transfusion

Noninfectious Infectious
Immediate Hepatitis (HBV, HCV & HDV)
 Transfusion reactions HIV (AIDS)
 Febrile non-hemolytic reaction Malaria
 Allergic reaction Cytomegalovirus
 Transfusion-related acute lung injury (TRALI) Syphilis
 Circulatory overload
 Air embolism
 Hypothermia
 Citrate intoxication
Delayed
 Transfusion-associated GVHD
 Iron overload
 Thrombophlebitis
Q. PANCYTOPENIA
Pancytopenia (anemia, neutropenia & thrombocytopenia)
Cause
 Aplastic anemia
 Myelodysplastic syndromes
 Bone marrow infiltration [Leukemia, Lymphoma, Myeloma]
 Megaloblastic anemia (vitamin B12 and folic acid deficiency)
 PNH
 Myelofibrosis
 Hypersplenism

Q. BONE MARROW TRANSPLANTATION

Indications
Oncological Nononcological
AML Aplastic anaemia
ALL Beta-thalassaemia major
CML Myelodysplastic syndrome
Multiple myeloma Paroxysmal nocturnal haemoglobinuria
Hodgkin’s & non-Hodgkin’s Bernard-Soulier syndrome
Neuroblastoma Chediak-Higashi syndrome
Severe combined immunodeficiency
Adenosine deaminase deficiency
X-linked agammaglobulinaemia
DiGeorge syndrome
Wiskott-Aldrich syndrome
Types of Bone Marrow Transplantation
 Syngeneic → Donor & recipient are identical-identical twins.
 Allogeneic → Donor & recipient are of different genetic origin, but of same species.
 Autologous → Removal of marrow → Chemo/Radiotherapy → re-transfer of patient’s own marrow
 Complications
 Graft versus host disease (GVHD)
 Opportunistic infections
.
Q. GRAFT VERSUS HOST DISEASE (GVHD)
Occurs following Allogenic transplantation of Blood, Marrow, Organs
Donor T lymphocytes (CD4+ and CD8+ T-cells) reacting against the recipient’s tissues/organs
Pathogenesis → Due to HLA mismatch
Types
 Acute GVH disease → Occurs < 100 days
 Chronic GVH disease → Occurs > 100 days
Clinical features
 Skin rash
 Diarrhea
 Liver dysfunction
 Keratoconjunctivitis sicca
 Lichenoid changes of buccal mucosa
 Sclerodermatous skin changes

BLOOD RELATED DRUGS

Antiplatelet
COX inhibitor P2Y12 inhibitor GP llb llla inhibitor Phosphodiesterase inhibitor
Aspirin Ticlopidine Abciximab Dipyridamole
Clopidogrel Eptifibatide Cilostazol
Prasugrel Tirofiban
Ticagrelor
Cangrelor
Anticoagulant
Parenteral Oral
ITI DTI DTI Xa inhibitors Coumarins
UHF Hirudin Ximelagatran Apixaban Warfarin
LMWH Lepirudin Dabigatran Rivaroxaban Bishydroxycoumarin
Fondaparinux Bivalirudin Edoxaban
Argatroban Betrixaban

LMWH
 Enoxaparin
 Fondaparinux
Indications
 Unstable angina
 Thrombosis associated with MI
 PE
 DVT
 Post-MI PCI & Stenting
Q. MEGALOBLASTIC ANAEMIA
Macrocytosis (MCV > 100 fL)
Causes
 B12 deficiency
o Malaborption (tropical sprue)
o Gastrectomy
o Intrinsic factor deficiency (pernicious anemia)
o Diphyllobothrium latum infestation
o Increased demand → Pregnancy, hyperthyroidism, disseminated cancer
o Imerslund-Grasbeck syndrome [Isolated B12 Malabsorption]
 B9 deficiency
o Malabsorptive states → Tropical sprue, Celiac disease
o Anticonvulsant therapy → Phenytoin, Phenobarbitone
o Anti-folate drug therapy → Methotrexate, Trimethoprim
o Increased demand → Pregnancy, hyperthyroidism, disseminated cancer
 Myelodysplastic syndrome
 Liver disease
 Reticulocytosis
 Hydroxyurea treatment
 Excess alcohol intake
Pathogenesis
Cobalamin & Folic acid are involved in DNA synthesis → Deficiency leads to impaired DNA synthesis

Delayed Nuclear maturation compared to Cytoplasmic maturation

Megaloblastic changes & Pancytopenia

Clinical features
 Anorexia, Hypotonia
 Hyperpigmentation of knuckles & terminal phalanges
 Fever (due to neutropenia)
 Bleeding (due to thrombocytopenia)
 Hepatosplenomegaly
 Diffuse Atrophic gastritis
 Achlorohydria
 Glossitis with Beefy red swollen tongue
 Bilateral peripheral neuropathy → Glove and sock distribution of numbness or paresthesia
 Hyper-Homocystinemia → Atherosclerosis
 Subacute demyelination/degeneration of dorsal & lateral tracts
o Ataxia
o Uncoordinated gait
o Impairment of vibration & position sense
Investigations
Peripheral Blood Peripheral smea Biochemical finding
Hemoglobin: decreased Macro-ovalocytes B12 deficiency
Hematocrit (PCV): decreased RBC → lack central pallor  Homocysteinuria
MCV - > 100 fL Hypersegmented neutrophils  Methylmalonateuria
MCH - decreased Pancytopenia B9 deficiency
MCHC - normal Howell-jolly bodies  Homocysteinuria
Anisopoikilocytosis  No Methylmalonateuria
Schillings test
 Differentiate B12 deficiency caused either by
o Pernicious anaemia
o Malabsorption
FIGLU excretion test
 Folic acid deficiency → FIGLU cannot be metabolized → excreted in urine unaltered
 FIGLU – Form-immino-glutamic acid
Management
 B12 deficiency
Hydroxocobalamin 1000 mcg twice during first week

1000 mcg weekly for 6 weeks

1000 mcg of cyanocobalamin per month for life-long

o Rapid regeneration of blood depletes iron reserves of body
 ferrous sulphate 200 mg daily given soon after commencement of treatment an
 Folate deficiency
o 5 mg of folic acid/day oral
o 350 mg daily is given for all pregnant women.
o Methotrexate therapy, Folinic acid 15 mg daily oral
 Treat the intercurrent infections (UTI or Respiratory infections)
 Underlying cause treat
Q. HEMOLYTIC ANAEMIA
Anemia resulting from increased red cell destruction in presence of normal or increased erythropoiesis
Characterized by
 Premature RBC destruction (< 120 days)
 Elevated erythropoietin (increased erythropoiesis)
 Increase hemoglobin catabolites (Bilirubin)
Causes
Intrinsic Extrinsic
 Hereditary spherocytosis Antibody-mediated destruction
 Hereditary elliptocytosis  Erythroblastosis fetalis
 G6PD deficiency  Transfusion reactions
 PNH  Drug-associated
 Pyruvate kinase deficiency  SLE
 Thalassemia Microangiopathic Hemolysis
 SCD  Hemolytic uremic syndrome
 DIC
 TTP
Infection
 Malaria
 Babesiosis
Hypersplenism
Defective Cardiac valves
Clinical features
 Extravascular hemolysis [Occurs in macrophages of spleen]
o Anemia, Jaundice
o Splenomegaly
o Mild decrease in haptoglobin (serum protein that binds to hemoglobin)
 Intravascular hemolysis
o Anemia, Jaundice
o Hemoglobinemia
o Severe decrease in Serum Haptoglobin
o Hemoglobinuria
o Hemosiderinuria
Investigations
Peripheral Blood Peripheral smear Bone Marrow
Hemoglobin - Decreased RBC Erythroid Hyperplasia
Reticulocyte count - Increased  Nucleated red cells M ; E ratio: decreased
 Spherocyte
 Sickle cell
 Target cell
 Acanthocyte
 Schistocyte
Q. HEREDITARY SPHEROCYTOSIS
Inherited abnormality of RBC membrane
Mutation in RBC membrane proteins such as
 Spectrin
 Ankyrin
 Protein 4.2
Pathogenesis
RBC membrane protein mutation

Membrane loss due to hemodynamic stress of blood flow

Decrease RBC surface area

Formation of Spherocytes

Spherocytes are rigid, inflexible

Premature destruction - Trapped and destroyed in spleen (extravascular Hemolysis)

Clinical features
 Anaemia
 Splenomegaly
 Jaundice
 Pigment gallstones
 Aplastic crisis [Upon superadded Parvovirus B19 infection]
 Hemolytic crisis [Upon superadded EBV infection]
Complications
 Gall-stones
 Aplastic crises
 Hemochromatosis
 Hepatic fail
Investigations
Peripheral smear Bone marrow Biochemical
Spherocytes Erythroid hyperplasia Serum bilirubin: raised.
RBCs without any central pallor Urine urobilinogen: increased
TLC: increased Serum haptoglobin: decreased.
Reticulocyte: increased
Osmotic fragility test → Increased osmotic fragility
Treatment
 Splenectomy
 Prior to splenectomy → polyvalent pneumococcal vaccine.
 Administration of prophylactic penicillin in post-splenectomy period
Q. SICKLE CELL ANEMIA
Qualitative defect in hemoglobin synthesis
Hereditary disorders of hemoglobin characterized by production of sickle hemoglobin (HbS)
Etiology
 Missense point mutation
 Substitution of glutamic acid by valine in 6th position of beta-globin chain
 It alters solubility & stability of hemoglobin
Pathogenesis
Low O2 tension or deoxygenation, HbS molecules undergo aggregation & polymerization

Aggregated HbS molecules form long needle-like fibers (known as tactoids) within RBC

RBC become elongated and assumes a shape like sickle Predisposes to stasis and vascular occlusion
Clinical Features
 Presence of HbF in first 6 months of life has a protective role [reduced aggregation of HbS]
 Symptoms appear after 6 months of age as HbF disappears.
 Sickling Crisis (Vaso-occlusive crisis)
o Blockage of microcirculation by sickled red cells -> hypoxic injury and infarction.
o Bone → Hand-foot syndrome, Dactylitis of bones of hands & feet
o Lung → acute chest syndrome (dangerous).
o Spleen → recurrent splenic infarction -> Auto-splenectomy
 Sequestration Crisis
Sudden trapping of blood in spleen or liver -> Rapid Congestive enlargement of organ

Drop in hematocrit leading to hypovolemia

 Increased Susceptible to acute infections
o Pneumonia due to Pneumococcus,
o Meningitis due to Streptococcus pneumoniae
o Osteomyelitis due to Salmonella
Investigations
Peripheral Blood Peripheral smear Serum Findings
Hemoglobin: Decreased. Anisopoikilocytosis Hyper-Bilirubinemia [Gallstones]
Hematocrit (PCV): Decreased. Sickle cell Raised Serum Iron, Ferritn
ESR: Reduced. Target cells Haptoglobin: reduced
Reticulocyte count: Increased Polychromatophilia [Reticulocytosis] Urobilinogen – Increased
Diagnostic/Confirmatory Tests
 Hemoglobin electrophoresis
 Estimation of HbF
 HPLC- High Performance Liquid Chromatography
Treatment
 Pneumococcal vaccination & penicillin prophylaxis
 Vigorous treatment of infection.
 Analgesic therapy for pain crisis
 Blood transfusion therapy
 Bone marrow transplantation
 Hydroxyurea → Increase HbF levels → Reduce Sickling
Q. THALASSEMIA (Cooley Anemia, Mediterranean Anemia)
Group of inherited disorders due to abnormality of globin production
Characterized by decreased or absence of synthesis of either alpha or beta-globin chain of adult hemoglobin [HbA]
Classification
 Beta-Thalassemia syndromes: Impaired synthesis of Beta-chains of globin.
 Alpha-Thalassemia syndromes: Impaired synthesis of Alpha-chains of globin.
Pathogenesis
Impaired or Absence of synthesis of One globin chain

Leads to inclusions of another globin chain inside RBC

RBC with single-globin chain inclusions are removed by Extravascular Hemolysis

Clinical features
 Moderate to severe anemia
 Untreated/untransfused children fail to thrive and die within 4–5 years of age
 Thalassemic facies (chipmunk face)
 Prominent forehead, cheekbones & upper jaw.
 Extramedullary hemopoiesis Hepatomegaly
 Marked splenomegaly
 Iron overload -> multiple blood transfusions -> secondary hemochromatosis (heart, liver & pancreas)
Investigations

Special Tests
 Fetal hemoglobin (HbF): increased
 Hemoglobin electrophoresis
 NESTROF test (Naked eye single tube red cell osmotic fragility test) - positive.
Radiological findings
 X-ray skull - hair on end (“crew-cut”) appearance -> due to extramedullary hematopoiesis
 long bones, metacarpals and metatarsals -> thinning of cortex, widening of medulla (marrow hyperplasia)
Treatment
 Blood transfusion is given periodically at 3-5 weeks intervals
 Folic acid supplements
 Human recombinant erythropoietin
 Allogenic bone marrow transplantation using a matched sibling donor -> curative treatment
Q. HEMOPHILIA
X-linked inherited bleeding disorders commonly affecting Male child
Classification
 Hemophilia A - deficiency of factor VIII [antihemophilic factor (AHF)]
 Hemophilia B (Christmas Disease) - deficiency of factor IX [Christmas factor]
 Hemophilia C - deficiency of factor XI [plasma thromboplastin antecedent (PTA)]
Clinical manifestations
 Excessive bleeding
 Contusions or hematomas at sites of minor trauma
 Epistaxis
 Bleeding after tooth extraction or tonsillectomy
 Hemarthrosis [knee, ankle & elbow] -- inflammation & degenerative changes → fixed joint
 Bleeding may occur into genitourinary tract, CNS, GIT, liver, spleen, peritoneal or pleural cavity
Complications
 Deforming arthritis & contractures
 Anemia

Treatment
 Severe bleeding - fresh whole blood
 Compression: pressure bandage
 Mild to moderate bleeding - fresh frozen plasma
 Factor VIII concentrate
 Recombinant factor VIII
 Desmopressin and darnazol
 Antifibrinolytic agents (tranexamic acid, epsilon-amino-caproic acid)
 Local application of thrombin powder
Leukaemias  Malignant neoplasms of haematopoietic stem cells, arising in bone marrow

Q. ACUTE MYELOID LEUKAEMIA

Age > 60 years
Aetiology
 Down’s syndrome
 Patau’s syndrome,
 Klinefelter’s syndrome
 Ataxia telengiectasia,
 Bloom’s syndrome
 Fanconi’s anaemia
 Radiation
 Occupational Chemical exposures.
FAB classification
M0  Minimally differentiated
M1  Without Maturation
M2  With Maturation
M3 -> ProMyelocytic
M4  Myelo-Monocytic
M5  Monocytic
M6  Erythroblastic
M7  Megakaryoblastic
Symptoms Sign
 Fatigue  Lymphadenopathy
 Weight loss  Hepatomegaly
 Anorexia  Splenomegaly
 Bruising/bleeding  Sternal
 Bone pain  Infection
 Granulocytic sarcomas  Haemorrhage
 Chloromas  DIC is MC in M3

Investigations
 RBC Normochromic normocytic anaemia
 WBC  Elevated
 Thrombocytopenia
 Bone marrow examination: > 20% blast cells
 Auer rods  Azuriphilic needle like structure in cytoplasm of Myeloblastic cells
 Serum Uric acid & LDH  Elevated.
Management
 Induction
o Cytarabine + Anthracycline ± Etoposide.
 Post Remission Management
o High dose Cytarabine – 3 g/m2/day on 1, 3, 5 day every 12 hourly.
o Bone marrow transplantation–Allogenic/Autologous
Q. CHRONIC MYELOID LEUKAEMIA (CML)
Age 25 - 60 years
Cytogenetics
 Philadelphia chromosomes (Ph)
o Reciprocal translocation between chromosomes 22 & 9
o Abelson (ABL) Fragment of chromosome 9 joins Breakpoint Cluster (BCR) Fragment
o Fusion gene codes for a Protein with Tyrosine kinase activity
Clinical Features
 Fever
 Lethargy
 Anorexia
 Weight loss
 Abdominal discomfort
 Massive splenomegaly (> 15 cm)
 Splenic friction Rub  indicates Splenic infarction
 Lymphadenopathy
 Cutaneous infiltration
Investigations
 Normocytic normochromic anaemia
 Thrombocytopenia
 WBC count  Markedly Raised.
 Leucocyte alkaline phosphatase  Absent in Granulocytes in CML
 Uric acid & ALP  increased
 Serum B12  increased (increase in transcobalamin III which is present in neutrophil granules)
 Bone marrow  Hypercellularity
Management
 Allogeneic or Syngeneic bone marrow transplant
 Tyrosine kinase inhibitor
o Imatinib
o Dasatinib
o Nilotinib
 Alpha interferon  induction & maintenance of remission
 Leukapheresis
 Splenectomy
Q. ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL)
Age 3–7 years.
Males > females
Etiology
 Radiation
 Down’s syndrome
 Bloom’s syndrome
 Fanconi’s anaemia
 Ataxia telengiectasia
 Viruses  EBV, HTLV.
FAB Classification
 L1  Small blasts, Scant Cytoplasm
 L2  Large blasts, Abundant Cytoplasm
 L3  Variable sized blasts, Vacuolated Cytoplasm
Clinical Features
 Fatigue
 Pallor
 Petechiae,
 Fever.
 Mucosal bleeding
 Bone pain
 Arthralgias
 Splenomegaly
 Hepatomegaly
 Lymphadenopathy,
 Signs of increased ICT  leukaemic infiltration of Meninges
Complications
 Aplastic anaemia
 Renal failure
 Hypoglycaemia
 Bone marrow necrosis
Investigations
 Anaemia
 Thrombocytopenia
 WBC count < 10,000/mm³
 Peripheral smear  Lymphoblasts
 Bone marrow  malignant Lymphoblasts
 Bone X-ray  Cortical defects
 CSF analysis  leukaemic cells
 Uric acid  Elevated
Management
 Induction  Vincristine + L – Asparaginase + Daunarubicin
 Consolidation  Methotrexate + 6-Mercaptopurine + Cytarabine + Cyclophosphamide.
 Maintenance  6-Mercaptopurine
 CNS prophylaxis  Intrathecal Methotrexate
Q. CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL)
Age > 45 years
Staging
 Stage 0  Absolute lymphocytosis (15 × 109/lL / 15,000/µL)
 Stage 1  Enlarged Lymph Nodes
 Stage 2  Enlarged Liver or Spleen
 Stage 3  Anaemia (Hb < 11 gm/dl)
 Stage 4  Platelets (< 100 × 109/lL / < 100,000/µL) ± Anaemia, Organomegaly
Clinical Features
 Weight loss
 Infection
 Bleeding
 Enlarged rubbery non-tender nodes
 Hepatosplenomegaly.
Investigations
 Coombs’ positive haemolytic anaemia
 WBC count  50 to 200 × 109/l / 50,000 to 200,000/µL
 Thrombocytopenia
 Total proteins & immunoglobulin  Decreased (B-lymphocytes fail to produce antibodies)
Management
 Ibrutinib + Flufarabine + Cyclophosphamide + Obninutuzumab

Q. IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

Thrombocytopenia of unknown etiology.
Etiology.
 Idiopathic production of antibody against platelet
 Associated with
o Lymphoma
o CLL
o HIV
o Connective tissue diseases.
Clinical Presentation
 Bleeding
o Epistaxis
o Bruising
o Hematuria
o Dysfunctional uterine bleeding
o GI bleeding.
o Petechiae, Purpura & Ecchymoses
Diagnosis
 Thrombocytopenia
 Antiplatelet antibodies
 Bone marrow  Megakaryocytic Hyperplasia
Treatment
 Prednisone
 Splenectomy (if platelet counts <10,000–20,000/mm³)
 IVIG
 Thrombopoietin  Romiplostim, Eltrombopag
Q. DEEP VEIN THROMBOSIS (phlebothrombosis)
 Semisolid clot in vein, with a high tendency to develop Pulmonary Embolism & Sudden Death
Causes Sites for DVT
 Trauma – to Leg, Ankle, Thigh  Internal iliac vein
 Immobility  Ilio-femoral/ Femoral Vein
o Bedridden patients  Popliteal vein
o Long distance air/bus travel (travellers  Soleal vein
thrombosis)  Axillary vein thrombosis
 Pregnancy
 Puerperium
 OCP use
 Polycythemia
 Deficiency of Antithrombin, protein C & S
 Factor V Leiden mutation
Clinical features
 Fever
 Tender, Warm, Shiny Swelling calf
 Homan’s sign  Dorsiflexion of foot with extended knee causes Tenderness in Calf
 Mose’s sign  Gentle squeezing of Lower part of calf is painful (Risk of Clot dislodgement)
 Features of Pulmonary embolism
o Chest pain
o Breathlessness
o Hemoptysis
 Linton’s test
o Application of tourniquet at Saphenofemoral Junction
o Patient is made to walk without removing the tourniquet
o After walk, limb is elevated → prominence of superficial veins → indicates DVT
Differential diagnosis Investigations
 Ruptured baker's cyst  Venous Doppler with Duplex scanning, Venogram
 Ruptured plantaris tendon  Radioactive I¹²⁵ fibrinogen study
 Calf muscle hematoma  Ventilation-perfusion scanning

Treatment
 Rest, bandaging the entire limb with crepe bandage
 Anticoagulants → LMWH, Warfarin, Phenindone
 Fibrinolysis → Streptokinase
 Thrombectomy using Fogarty’s catheter
 IVC filter → prevents thrombus from reaching the heart
 Palma operation
o In ilio-femoral thrombosis
o ▪ Femoral vein below the block is Anastomosed to opposite femoral vein
 May-Hunsin operation
o In popliteal vein thrombosis
o Popliteal vein below the block is anastomosed to Long saphenous vein
Q. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
Consumptive coagulopathy disorder occurring as secondary complication in variety of diseases.
Diseases Associated with DIC
 Infections (Gram-negative sepsis, Meningococcemia, Histoplasmosis, Malaria, Aspergillosis)
 Neoplasms (carcinomas of Pancreas, Prostate, Stomach, Lung)
 Obstetric complications (Septic Abortion, Abruptio Placentae, Amnioti fluid embolism)
 Massive Trauma, Burns, or Surgery
 Others (Snakebite, Shock, Heat Stroke, Liver Disease).
Clinical features.

Investigations
 Platelet count  thrombocytopenia
 Prothrombin time  Prolonged
 PTT  Prolonged
 Clotting time  Prolonged.
 Fibrinogen  Low
 D dimers in urine  Increased
 Peripheral film  Schistocytes
Management
 Treat underlying cause
 Correction of precipitating factors like Acidosis, Dehydration & Hypoxia
 Correction of Platelet or Factor deficiencies
 Prevention of Sudden catastrophic Haemorrhage (GI bleed or intracranial bleed)
Q. SPLENOMEGALY
Mild (< 5cm) Moderate (5 – 8 cm) Massive (> 8 cm)
Congestive cardiac failure Viral hepatitis Chronic myeloid leukaemia
Malaria Cirrhosis Myeloid metaplasia
Typhoid Lymphomas Myelofibrosis
Miliary tuberculosis Leukaemias Hairy cell leukaemia
Leptospirosis Infectious mononucleosis Gaucher’s disease
HIV Haemolytic anaemias Niemann-Pick disease
Infective endocarditis Splenic infarcts Sarcoidosis
Septicaemia Splenic abscess Thalassaemia major
SLE Amyloidosis Chronic malaria
Rheumatoid arthritis Haemochromatosis Kala-azar
Thalassaemia minor Polycythaemia Congenital syphilis
Portal vein obstruction
Schistosomiasis

Q. APPLICATION OF STEM CELL TRANSPLANTATION

POISONING
Q. PARACETOMOL / ACETAMINOPHIN POISONING
Recommended dose of acetaminophen
 Adults, is 650 mg - 1000 mg every 4 - 6 hours, upto 4 grams/day.
 Children, is 15 mg/kg every 6 hours, upto 60 mg/kg/day.
Toxicity dose
 Adults → 7.5 g/day
 Children → 140 mg/kg
Toxicokinetics
 Overdose → metabolized into NAPQ1 by cytochrome P450 → Excess NAPQ1 depletes Glutathione →
NAPQ1 binds to hepatic macromolecules causing irreversible hepatic necrosis
Four clinical stages of paracetamol toxicity
Stage 1 30 mins - 24 hours
 Anorexia
 Nausea
 Vomiting
 Pallor
 Diaphoresis
Stage 2 1 - 2 days
 Pain in Upper abdomen
 Oliguria
 Liver dysfunction (Raised Bilirubin, SGOT, SGPT)
Stage 3 2 - 4 days
 GI symptoms
 Renal failure
 Coagulopathies
 Metabolic acidosis
 Encephalopathy
Stage 3 4 days - 2 weeks
 Resolution of liver dysfunction

Evaluation
 Serum levels of the drug
 Urine drug screen → Co-ingestion of other drugs
 Liver function tests (LFTs)
 Coagulation profile (PT/INR).
 EKG
 BMP, CMP
 Rumack-Matthew Nomogram → Monito Toxicity in Single Acute Poisoning
Treatment
 GI decontamination using Activated Charcoal
 Antidote Of Choice → N-acetyl-L-cysteine
o Loading dose → 140 mg/kg
o Maintenance dose → 70 mg/kg at 4-hour intervals
Q. BARBITURATE POISONING
Overdose → 2 – 10 gm
Clinical features
 Restlessness
 Tremors
 Hyperthermia
 Sweating
 Anxiety
 Seizures
 Circulatory failure → Hypotension, Bradycardia
 Respiratory failure → Cyanosis
 Potentially death.

Treatment / Management
 No specific antidote for overdose
 Supportive therapy
 Assessing patient’s airway, breathing, & circulation.
 Intubation & mechanical ventilation
 Activated charcoal via nasogastric tube.
 Forced alkaline diuresis
 Haemodialysis
 Bemegride → CNS stimulant that increases respiration [treatment for respiratory depressant]

Q. BENZODIAZEPINE TOXICITY
Clinical features
 Central nervous system (CNS) depression
o Slurred speech
o Ataxia
o Altered mental status
 Respiratory depression
Evaluation
 Urine drug screen
 Liver function tests (LFTs)
 Coagulation profile (PT/INR).
 EKG
 BMP, CMP
Treatment / Management
 Endotracheal intubation
 Activated charcoal
 Haemodialysis
 Antidote → Flumazenil [reverse benzodiazepine-induced sedation]
Q. OP POISONING
Toxicokinetics
 Organophosphate molecules absorbed via skin, inhalation, gastrointestinal tract.
 molecule binds & inactivates acetylcholinesterase enzyme
 Leads to overabundance of acetylcholine within synapses & neuromuscular junctions.
 Overstimulation of nicotinic & muscarinic receptors
Clinical features
Nicotinic receptors in Neuro-Muscular junction Muscarinic effects
 Fasciculations  D = Defecation/diaphoresis
 Myoclonic jerks.  U = Urination
 Flaccid paralysis because of depolarizing block.  M = Miosis
Nicotinic receptors in adrenal glands  B = Bronchospasm/bronchorrhea
 Hypertension  E = Emesis
 Sweating  L = Lacrimation
 Tachycardia  S = Salivation

Evaluation
 RBC Acetylcholinesterase activity
 CBC
 Glucose levels
 Troponin
 Liver & Renal function
 Arterial blood gas
 ECG → sinus bradycardia due to parasympathetic activation
Treatment / Management
 Decontaminate the patient
 Activated charcoal
 Endotracheal intubation
o Succinylcholine must be avoided during intubation as it prolongs paralysis.
 Cardiac monitoring
 Pulse oximetry
 Definitive treatment → atropine [abolishes muscarinic symptoms]
o Adults → 2 - 5 mg IV
o Children → 0.05 mg/kg IV
 Pralidoxime (2-PAM) [abolishes nicotinic symptoms]
o Mechanism → reactivating the phosphorylated AChE
o Adults → 30 mg/kg over 30 minutes
o Children → 20 to 50 mg/kg over 30 minutes
 Atropine must be given before 2-PAM to avoid worsening of muscarinic-mediated symptoms
Q. METHANOL TOXICITY
Lethal dose → 30 to 240 mL or 1g/kg
Toxicokinetics
 After absorption and follow a zero-order elimination rate.
 Metabolism occurs in liver by oxidation via alcohol dehydrogenase & aldehyde dehydrogenase
o Alcohol dehydrogenase oxidizes methanol → formaldehyde
o Aldehyde dehydrogenase oxidizes formaldehyde → formic acid.
o Each of these two oxidation steps is associated with a reduction of NAD to NADH
 Formaldehyde & formic acid → Increases Anion Gap → Metabolic acidosis

History and Physical

 Nausea, vomiting, & abdominal pain
 Hyperventilation [due to metabolic acidosis]
 Retinal toxicity [Blurry Vision, Decreased Visual Acuity, Photophobia, Halo Vision]
 CNS depression
Evaluation
 Gas chromatography → Measuring Toxic alcohol concentrations
 BMP
 CMP
 LFT
 RFT
Treatment
 Supportive care
 Ethanol
 Dialysis
 Folate therapy
 Fomepizole → antidote for toxic alcohols, [mechanism of action = inhibition of alcohol dehydrogenase]
o Loading dose → 15 mg/kg
o Maintenance dose → 10 mg/kg every 12 hours for 4 doses
Q. CYANIDE POISONING
Toxicokinetics
Cyanide reversibly binds to ferric ions of Cytochrome oxidase within the mitochondria

Inhibition of cellular respiration

Inhibits oxidative phosphorylation → Inhibition of cellular respiration → cellular hypoxia

History and Physical

 Headache
 Dizziness
 Confusion
 Mydriasis
 Seizures
 Altered consciousness.
 Hypotension & bradycardia
 Cherry red colour due to excess oxygen bloodstream
Evaluation
 CBC
 Electrolytes
 Plasma lactate
 Urine tox screen
 Arterial blood gas
 Carboxyhemoglobin level
 Chest x-ray
 EKG
Management
 Stabilize patient's airway, breathing, and circulation.
o mouth-to-mouth resuscitation is contraindicated, because of risk to provider of CPR
 Decontamination → Removal of clothing, Washing of exposed areas
 Gastrointestinal decontamination→ activated charcoal
 Hydroxocobalamin [antidote of choice]
o 5 grams IV over 15 minutes
o Antidote can turn urine dark red; this is not due to myoglobinuria
Q. CARBON-MONOXIDE POISONING
Toxicokinetics
 CO binds to hemoglobin forming carboxyhemoglobin (COHb)
 Has 220% greater affinity to hemoglobin than oxygen
 Reduces oxygen-carrying capacity of hemoglobin → leads to cellular hypoxia
 Hemoglobin concentration & PO2 of blood will be normal, but oxygen content of blood is reduced
 CO also binds to Cytochrome C oxidase in electron transport chain & inhibits mitochondrial respiration
History and Physical
 Headache
 Dizziness
 Weakness
 Tachycardic & Tachypneic.
 Altered consciousness
 Disorientation
 Retinal hemorrhages & papilledema.
 Cherry red nail beds & mucous membranes are usually post-mortem findings

Evaluation
 ABCs (airway, breathing, and circulation)
 Supplemental oxygen is the cornerstone of treatment.
 Arterial blood gas sample
 CBC
 Electrolytes
 BUN & creatinine levels
 Troponin
 ECG → checked for signs of ischemia.
 CT head → global pallidus haemorrhage

Treatment / Management
 Supplemental oxygen [Carbogen (5% CO2 + 95% oxygen)] → cornerstone of treatment for CO poisoning
 Hyperbaric oxygen therapy
Q. PLASMAPHERESIS
Therapeutic Extracorporeal Removal, Return or Exchange of blood plasma or components
Indications
Category 1 Category 2 Category 3 Category 4
GBS APLA HSP Amyloidosis
ANCA-associated RPGN Cryoglobulinemia SLE Dermatomyositis

Goodpasture syndrome Multiple sclerosis Scleroderma HELLP syndrome

FSGS Neuromyelitis Optica Autoimmune haemolytic anaemia

Overdose Heparin induced thrombocytopenia

Myasthenia gravis
IgA nephropathy
TT purpura Envenomation
Aplastic anaemia
Wilson disease Poisoning
PANDAS
Refsum disease

Q. METHEMOGLOBINEMIA
Life-threatening potential in which diminution of oxygen-carrying capacity of circulating haemoglobin due to
conversion of iron ions from reduced ferrous [Fe2+] state to oxidized ferric [Fe3+] state
Causes
 Congenital methemoglobinemia
 Acquired methemoglobinemia
o Exposure to direct oxidizing agents (benzocaine & prilocaine)
o Exposure to indirect oxidation (nitrates)
o Exposure to metabolic activators (aniline & dapsone)

Q. CHELATING AGENTS
Used to reduce blood and tissue levels of injurious heavy metals
Example
 Arsenic, Lead, Mercury → Dimercaprol
 Copper Chelators → Penicillamine, Trientine. Zinc
 Iron Chelators
o Deferasirox
o Deferiprone
o Deferoxamine
ACUTE MEDICINE AND CRITICAL ILLNESS
Q. SHOCK
 State of cellular & tissue hypoxia with Circulatory failure & poor perfusion
Causes
1. Hypovolemic shock → Reduction in total blood volume
 Haemorrhage
 Severe burns
 Vomiting & diarrhoea
2. Cardiac shock
 Acute MI
 Acute carditis
 Pulmonary embolism
 Drug induced
 Cardiac tamponade
 Arrhythmias
3. Septic shock → Bacterial infection with release of toxins into circulatory system
4. Neurogenic / Vasovagal shock
 Sudden anxious stimuli causing severe splanchnic vessels vasodilation
 Patient goes into cardiac arrest or recovers spontaneously
 Spinal cord injury/anaesthesia can cause neurogenic shock
5. Anaphylactic shock → Type 1 hypersensitivity reaction 6
6. Respiratory causes
 Atelectasis
 Thoracic injury
 Tension pneumothorax
7. Other causes
 Adrenal insufficiency (Addison’s disease)
 Myxedema
Pathophysiology of Shock

Any cause of shock

Low cardiac output Decreased renal blood flow

Decreased GFR → Decreased urine output

Activation of RAAS → Ag-2 and Aldosterone mediated Vasoconstriction and Salt/Water retention respectively

ADH is released Further retention of water

Persistence of shock → further decrease in cardiac output

Hypoxia → anaerobic metabolism

Lactic acidosis

Cell wall damage

Na and Ca enter the cell

K leaks out of the cell

Hyperkalaemia, Hyponatremia, Hypocalcemia

Intracellular lysosome breakdown → release of proteolytic enzymes

SICK CELL SYNDROME

SIRS (systemic inflammatory response syndrome)

Due to Vasodilation, Increased vascular permeability, DIC, Sick cell syndrome

MODS (multiorgan dysfunction syndrome) → of lungs, kidney, liver, brain (Irreversible shock)
Effects of shock

Investigations
Treatment
 Acute critical care management
o A – airway
o B – breathing, bleeding
o C – circulation
 Fluid replacement
o Ringer lactate
o Hartmann's solution
o Plasma expander (haemaccel)
o Blood transfusion
 Inotropic agents
o Epinephrine - Anaphylactic shock
o Norepinephrine – vasodilatory/septic shock
o Dobutamine - cardiogenic shock
 Acidosis → IV sodium bicarbonate
 Steroid (hydrocortisone) → Improves perfusion, decreases systemic inflammatory effects
 Pain control → Morphine 4mg IV
 Ventilator & ICU care management
 MAST trouser (military anti-shock trouser)
o Provides circumferential external pressure of 40mmHg
o Wrapped around lower limbs and abdomen, inflated with required pressure
o It redistributes the existing blood & fluid towards centre
Q. SEPTIC SHOCK
Widespread infection & toxin release causing multiorgan failure and dangerously low blood pressure
Pathogenesis

Stages of septic shock

 Hyperdynamic (warm) stage
o Reversible stage
o Fever, Tachycardia, Tachypnea
o Pyrogenic response is intact
 Hypodynamic Hypovolemic stage (cold stage)
o Pyrogenic response is lost
o Patient is in decompensated stage
o Irreversible shock leading to MODS
Treatment
 Correction of fluid & electrolyte
 Blood transfusion (blood perfusion is most important)
 Appropriate antibiotics
 Treatment of underlying cause
o Drainage of abscess
o Laparotomy for peritonitis
o Resection of gangrenous bowel
o Wound excision
 Norepinephrine → DOC for septic shock
 High dose steroid therapy → counteract effects off toxaemia
Q. ANAPHYLACTIC SHOCK
Severe Type 1 HSN reaction towards allergens
Pathogenesis
 Exposure to allergen → Primary Sensitization → IgE coats Mast cells → Subsequent allergen exposure →
Secondary Sensitization → Release of Anaphylactic mediators from Mast cells
 Anaphylactic mediators are
o Histamine
o Heparin
o Serotonin
o Leucotrienes (LTC4 , LTD4 , LTE4)
o Prostaglandins
o ECF-A (eosinophil chemotactic factor of anaphylaxis)
o NCF (neutrophil chemotactic factor)
o Platelet-activating factor
Causes of Anaphylactic shock
Drugs Biological agents Proteins Insect bites
Penicillin Blood & its components Peanut Honey bee
Cephalosporin Tetanus antitoxin Fish Wasps
Tetracycline Rabies antitoxin Egg
Sulphamethoxazole Diphtheria antitoxin Milk
Vancomycin Vaccines Soy products
Diuretics
B-blockers
Clinical features
Mucocutaneous Gastrointestinal
 Pruritus  Nausea, vomiting
 Flushing  Abdominal cramps
 Urticaria  Diarrhoea
 Angioedema
 Conjunctival injection
Respiratory Cardiovascular
 Bronchospasm → Dyspnoea, Wheeze  Tachycardia
 Laryngeal oedema → Stridor  Hypotension
 Pulmonary oedema  Arrhythmia
 Syncope
Treatment
 Epinephrine 0.5 mL of a 1: 1000 solution IM (lateral thigh) & repeated at 5 mins intervals
 Severe cases, 1 mL of 1: 100,000 solution IV over 2-10 minutes.
 Oxygen 4-6 L/min
 Endotracheal intubation or Tracheostomy [intermittent positive pressure ventilation] I
 Hypotension → Intravenous Fluids, Dopamine.
 Bronchodilators → nebulised Salbutamol.
 Hydrocortisone 200 mg IV stat → Treat persistent Bronchospasm & Hypotension)
 Diphenhydramine 50-80 mg IM/IV.
 Ranitidine (H2 blocker), 50 mg IV
Q. SYNCOPE
Transient loss of consciousness due to inadequate cerebral blood flow 20 to abrupt decrease in cardiac output
If syncope lasts for
 5 seconds → dizziness
 10 seconds → unconscious
 15 seconds → convulsions
Causes
Cardiac Drugs Hypovolaemia Reflexes
Extreme bradycardia Antihypertensives Haemorrhage Vasovagal syncope
Heart block B- blockers Vasodilators Fluid loss Orthostatic hypotension
SVT Diabetic precoma Hypersensitive carotid sinus
Aortic stenosis Tussive (cough) syncope
HOCM Micturition syncope
Left atrial tumours Deglutition syncope
Pulmonary stenosis Defaecation syncope
Pulmonary HTN
Pulmonary embolism

Q. DELIRIUM
Acute confusional state characterised by
 Periods of agitation
 Heightened mental activity
 Increased wakefulness
 Hallucinations
 Motor hyperactivity
 Autonomic stimulation.
 Impairment of attention
Causes
 Head injury
 CVA, Cerebral infections, Epilepsy
 Hypoglycaemia, DKA
 Hypoxia Renal or Hepatic failure
 Electrolyte or acid-base imbalance
 Wernicke’s encephalopathy
 Septicaemia
 SBE
 Heat stroke
 Hypothermia
 Toxins → Alcoholic, Barbiturates, narcotics withdrawal
 Acute mania
 Schizophrenia (auditory hallucinations)
 Hysteria
Alcohol withdrawal → delirium tremens
 Delirium
 Tremors
 Visual hallucinations

Q. ACUTE RESPIRATORY DISTRESS SYNDROME

Acute lung injury characterized by Increased Permeability of alveolar-capillary membrane & pulmonary edema
Etiology
 Sepsis
 Trauma
 Disseminated intravascular coagulation
 Drug overdose
 Inhalation of toxins
 Goodpasture syndrome
 Systemic lupus erythematosus
 Drowning
 Period after bypass surgery
ARDS consists of 3 phases
1. Exudative
2. Proliferative
3. Fibrotic
Clinical features
 Severe hypoxemia
 Decreased pulmonary compliance
 Dyspnoea
 Increased respiratory rate
 Diffuse rales & rhonchi
Evaluation
 Chest x-ray → Diffuse Interstitial or Alveolar Infiltrates;
 ABGs → decreased Pao2 & increased PaCO2
 Swan-Ganz catheter
o Normal Cardiac Output
o Normal Capillary Wedge Pressure
o Increased Pulmonary Artery Pressure Treatment.
Treatment
 Treat underlying disorder
 Mechanical support → Positive End-Expiratory Pressure [PEEP]
 Nitric oxide inhalation → Reduces Pulmonary artery pressure & improves oxygenation
Q. MECHANICAL VENTILATION
Mechanical support to ventilatory function of respiratory & and improve oxygenation by positive pressure
Indications for Mechanical Ventilation
 Respiratory rate > 35/min
 Inspiratory force < 25 cm of H2O
 Vital capacity < 10-15 ml/kg
 PaO2 < 60 mm Hg with FiO2 > 60 %
 PaCO2 > 50 mm Hg with pH < 7.35
 Absent gag or cough reflex
Modes of Ventilation
 Control Mode Ventilation (CMV)
 Assist Control Mode Ventilation (ACMV)
 Synchronised Intermittent Mandatory Ventilation (SIMV)
 Pressure Support Ventilation (PSV)
 Continuous Positive Airway Pressure (CPAP)
 Positive End Expiratory Pressure (PEEP)
 Inverse ratio ventilation (IRV)
 Non-invasive Mechanical Ventilation
Contraindications
 Respiratory arrest
 Cardiovascular instability (Hypotension, arrhythmias, MI)
 High aspiration risk—viscous or copious secretions
 Craniofacial trauma
 Extreme obesity
Complications
 Aspiration
 Pneumonia
 Tracheal stenosis
 Barotrauma
o Air-embolism
o Subcutaneous emphysema
o Pneumopericardium
o Pneumoperitoneum
o Pneumomediastinum
o Pneumothorax