Final Revision Notes — Set 1
Peptic Ulcer Disease, Ulcerative Colitis and Crohn
Disease
1. Peptic Ulcer Disease
Definition
Peptic ulcer is a chronic mucosal defect occurring in an area exposed to acid and pepsin,
extending through the muscularis mucosae into the submucosa or deeper.
Common sites
● First part of duodenum — most common
● Gastric antrum, usually along lesser curvature
● Gastroesophageal junction
● Gastrojejunal anastomosis
● Meckel diverticulum containing ectopic gastric mucosa
Etiology
● Helicobacter pylori
● NSAIDs
● Smoking
● Alcohol
● Severe physiological stress
● Zollinger–Ellison syndrome
● Corticosteroids, especially with NSAIDs
Pathogenesis
Peptic ulcer develops due to an imbalance between aggressive and protective factors.
Aggressive factors
● Gastric acid
● Pepsin
● H. pylori
● NSAIDs
● Bile reflux
Protective factors
● Mucus
● Bicarbonate
● Prostaglandins
● Adequate mucosal blood flow
● Epithelial regeneration
Role of H. pylori
H. pylori produces urease
↓
Ammonia formation
↓
Organism survives in acidic stomach
↓
Chronic gastritis and mucosal injury
↓
Peptic ulcer
Role of NSAIDs
NSAIDs inhibit COX
↓
Reduced prostaglandins
↓
Reduced mucus and bicarbonate
+
Reduced mucosal blood flow
↓
Ulcer formation
Morphology
Gross
● Solitary
● Round or oval
● Sharply punched-out
● Clean, smooth base
● Straight walls
● Mucosal folds radiate toward the ulcer
● Benign margins are not heaped up
Microscopy
Four layers from surface to depth:
1. Necrotic fibrinoid debris
2. Neutrophilic inflammatory exudate
3. Granulation tissue
4. Fibrous scar
Clinical features
● Burning or gnawing epigastric pain
● Dyspepsia
● Nausea and vomiting
● Hematemesis
● Melena
● Iron-deficiency anemia
Gastric ulcer
● Pain worsens soon after meals
● Weight loss is common
Duodenal ulcer
● Pain occurs 2–3 hours after meals
● Relieved by food or antacids
● Nocturnal pain may occur
Complications
● Hemorrhage
● Perforation → peritonitis
● Penetration into adjacent organs, especially pancreas
● Gastric outlet obstruction due to fibrosis
● Gastric ulcer must be biopsied to exclude malignancy
● Duodenal ulcers are almost never malignant
2. Ulcerative Colitis
Definition
Ulcerative colitis is a chronic relapsing inflammatory bowel disease involving the rectum
and colon in a continuous manner, with inflammation mainly limited to the mucosa and
submucosa.
Etiopathogenesis
The exact cause is unknown.
Contributing factors:
● Genetic susceptibility
● Abnormal immune response to intestinal microbes
● Defective epithelial barrier
● Environmental factors
Genetic susceptibility
↓
Abnormal mucosal immune response
↓
Chronic mucosal inflammation
↓
Ulceration
Distribution
● Always begins in rectum
● Extends proximally
● Continuous involvement
● No skip lesions
● Limited to colon
● Mainly mucosal and submucosal
Morphology
Gross
● Red, granular and friable mucosa
● Broad superficial ulcers
● Continuous involvement
● Pseudopolyps
● Shortened colon
● Loss of haustra
● Lead-pipe appearance
Microscopy
● Mucosal and submucosal inflammation
● Cryptitis
● Crypt abscesses
● Mucosal ulceration
● Distorted and branched crypts
● Goblet-cell depletion
● No granulomas
Clinical features
● Bloody diarrhea
● Mucus in stool
● Abdominal pain
● Urgency
● Tenesmus
● Fever
● Weight loss
● Anemia
Complications
● Toxic megacolon
● Severe hemorrhage
● Perforation
● Colorectal carcinoma
● Primary sclerosing cholangitis
● Arthritis
● Uveitis
● Skin lesions
Carcinoma risk increases with
● Long duration
● Extensive colonic involvement
● Severe inflammation
One-line summary
Ulcerative colitis is a continuous mucosal disease of the colon beginning in the
rectum, characterized by bloody diarrhea, crypt abscesses, pseudopolyps and
increased colorectal carcinoma risk.
3. Crohn Disease
Definition
Crohn disease is a chronic relapsing transmural inflammatory bowel disease that may
involve any part of the gastrointestinal tract, commonly the terminal ileum, and is characterized
by skip lesions.
Etiopathogenesis
The exact cause is unknown.
Factors include:
● Genetic susceptibility
● Abnormal immune response to intestinal microbes
● Defective epithelial barrier
● Environmental factors
● Smoking
Genetic susceptibility
↓
Abnormal immune response
↓
Transmural inflammation
↓
Ulcers, fibrosis, strictures and fistulas
Distribution
● Anywhere from mouth to anus
● Terminal ileum commonly involved
● Patchy involvement
● Skip lesions
● Rectum may be spared
● Entire bowel wall may be involved
Morphology
Gross
● Thickened bowel wall
● Narrowed lumen
● Deep linear fissuring ulcers
● Cobblestone appearance
● Skip lesions
● Creeping fat
● Strictures
● Fistulas
Microscopy
● Transmural inflammation
● Lymphoid aggregates
● Deep fissuring ulcers
● Non-caseating granulomas
● Fibrosis
● Neural hypertrophy
Granulomas are characteristic but may be absent.
Clinical features
● Chronic diarrhea, usually non-bloody
● Abdominal pain
● Weight loss
● Low-grade fever
● Malabsorption
● Perianal disease
● Fistula discharge
Complications
● Fistulas
● Strictures
● Intestinal obstruction
● Abscess formation
● Perforation
● Malabsorption
● Vitamin B12 deficiency
● Gallstones
● Renal stones
● Increased colorectal carcinoma risk
Ulcerative Colitis versus Crohn Disease
Feature Ulcerative colitis Crohn disease
Site Colon and rectum Anywhere from mouth to anus
Rectum Always involved May be spared
Pattern Continuous Skip lesions
Depth Mucosa and submucosa Transmural
Diarrhea Bloody Usually non-bloody
Ulcers Broad and superficial Deep fissuring
Gross Pseudopolyps, lead-pipe Cobblestone mucosa, creeping fat
appearance colon
Granulomas Absent Non-caseating granulomas may
occur
Fistulas Uncommon Common
Strictures Uncommon Common
Toxic megacolon Common complication Less common
Cancer risk Markedly increased Increased
Rapid recall lines
● Peptic ulcer: acid-peptic injury exceeds mucosal defence.
● Ulcerative colitis: continuous, rectum involved, mucosal, bloody diarrhea.
● Crohn disease: skip lesions, transmural, fistulas, granulomas.
Final Revision Notes — Set 2
Fatty Liver, Cirrhosis, Portal Hypertension and
Hepatocellular Carcinoma
4. Fatty Liver
Definition
Fatty liver or hepatic steatosis is the abnormal accumulation of triglycerides within
hepatocytes.
Causes
● Alcohol abuse
● Obesity
● Diabetes mellitus
● Hyperlipidemia
● Protein malnutrition
● Drugs and toxins
● Non-alcoholic fatty liver disease
Pathogenesis
Alcohol / Obesity / Diabetes
↓
Increased fatty acid entry into liver
+
Increased triglyceride synthesis
+
Decreased fatty acid oxidation
+
Decreased lipoprotein secretion
↓
Triglyceride accumulation in hepatocytes
↓
Fatty liver
Morphology
Gross
● Enlarged liver
● Soft
● Yellow
● Greasy
● Rounded margins
Microscopy
● Clear fat vacuoles in hepatocytes
● Usually macrovesicular steatosis
● Nucleus pushed to the periphery
● Initially more prominent around central veins
● Later may become diffuse
Clinical Features
● Often asymptomatic
● Hepatomegaly
● Mild right upper abdominal discomfort
● Mild elevation of AST and ALT
Complications
● Steatohepatitis
● Fibrosis
● Cirrhosis
● Liver failure
● Hepatocellular carcinoma
One-line summary
Fatty liver is triglyceride accumulation within hepatocytes, commonly due to alcohol
or metabolic syndrome, and is usually reversible in early stages.
5. Cirrhosis
Definition
Cirrhosis is a chronic progressive liver disease characterized by diffuse fibrosis and
regenerative nodules, causing distortion of normal liver architecture and impaired liver
function.
Causes
● Chronic alcohol abuse
● Chronic hepatitis B
● Chronic hepatitis C
● Non-alcoholic steatohepatitis
● Autoimmune hepatitis
● Hemochromatosis
● Wilson disease
● Primary biliary cholangitis
● Chronic biliary obstruction
Pathogenesis
Chronic liver injury
↓
Hepatocyte death
↓
Activation of hepatic stellate cells
↓
Collagen deposition
↓
Bridging fibrosis
↓
Regeneration of surviving hepatocytes
↓
Regenerative nodules
↓
Distortion of liver architecture
↓
Portal hypertension + Liver failure
Morphology
Gross
● Early liver may be enlarged
● Later liver becomes shrunken
● Firm consistency
● Yellow-brown colour
● Irregular nodular surface
Microscopy
● Bridging fibrosis
● Regenerative nodules
● Distorted lobular architecture
● Chronic inflammatory infiltrate
● Loss of normal portal-central vein relationship
Clinical Features
● Fatigue
● Weakness
● Jaundice
● Hepatomegaly in early stage
● Ascites
● Splenomegaly
● Pedal edema
● Easy bruising
● Spider angiomas
● Palmar erythema
● Confusion in hepatic encephalopathy
Complications
Portal hypertension
● Esophageal varices
● Splenomegaly
● Ascites
● Caput medusae
● Hypersplenism
Liver failure
● Hypoalbuminemia → edema and ascites
● Reduced clotting factors → bleeding
● Reduced detoxification → hepatic encephalopathy
Other complications
● Hepatorenal syndrome
● Hepatocellular carcinoma
One-line summary
Cirrhosis is diffuse fibrosis with regenerative nodules causing architectural
6. Hepatitis C
Definition
Hepatitis C is an infectious disease of the liver caused by the hepatitis C virus (HCV), an
enveloped single-stranded RNA virus. It commonly progresses to chronic hepatitis.
Mode of transmission
● Blood transfusion and blood products
● Intravenous drug abuse and shared needles
● Needle-stick injury
● Hemodialysis
● Tattooing or unsafe injections
● Less commonly, sexual and vertical transmission
Pathogenesis
HCV shows frequent genetic variation and escapes the immune response.
HCV infection
→ immune-mediated hepatocyte injury
→ chronic inflammation
→ hepatocyte destruction
→ fibrosis
→ cirrhosis
→ hepatocellular carcinoma
Morphology
Acute hepatitis
● Hepatocyte ballooning
● Spotty necrosis
● Mononuclear inflammatory infiltrate
● Councilman bodies may be seen
Chronic hepatitis C
● Portal mononuclear inflammation
● Portal lymphoid aggregates
● Interface hepatitis
● Fatty change
● Progressive bridging fibrosis and cirrhosis
Clinical features
Acute infection is often asymptomatic or mild.
Chronic disease may present with:
● Fatigue
● Anorexia
● Jaundice
● Hepatomegaly
● Features of chronic liver disease
Diagnosis
● Anti-HCV antibody: indicates exposure
● HCV RNA by PCR: confirms active infection
● Liver enzymes may be raised
Complications
● Chronic hepatitis
● Cirrhosis
● Hepatocellular carcinoma
● Mixed cryoglobulinemia
8. Alcoholic Liver Disease
Definition
Alcoholic liver disease refers to liver injury caused by chronic excessive alcohol intake.
Stages
1. Alcoholic fatty liver
2. Alcoholic hepatitis
3. Alcoholic cirrhosis
Pathogenesis
Alcohol is metabolized mainly in the liver to acetaldehyde.
Alcohol metabolism causes:
● Increased NADH:NAD⁺ ratio
● Accumulation of triglycerides
● Acetaldehyde-mediated cellular injury
● Free-radical formation
● Inflammation and hepatocyte necrosis
● Activation of stellate cells and fibrosis
Alcohol
→ fatty change
→ hepatocyte injury and inflammation
→ fibrosis
→ cirrhosis
Morphology
1. Alcoholic fatty liver
Gross
● Enlarged
● Soft
● Yellow
● Greasy liver
Microscopy
● Fat vacuoles in hepatocytes
● Initially centrilobular, later diffuse
2. Alcoholic hepatitis
Microscopy
● Hepatocyte ballooning and necrosis
● Mallory-Denk bodies
● Neutrophilic infiltration
● Fatty change
● Pericellular fibrosis
3. Alcoholic cirrhosis
Gross
● Initially enlarged and yellow
● Later small, shrunken, firm and nodular
● Usually micronodular initially
Microscopy
● Regenerative nodules
● Fibrous septa
● Distortion of liver architecture
Clinical features
● Hepatomegaly
● Jaundice
● Abdominal pain
● Ascites
● Portal hypertension
● Features of liver failure
Complications
● Portal hypertension
● Ascites
● Hepatic encephalopathy
● Liver failure
● Hepatocellular carcinoma
9. Pleomorphic Adenoma
Definition
Pleomorphic adenoma is the most common benign salivary gland tumour, usually arising in
the parotid gland.
It is also called a mixed tumour because it contains epithelial and myoepithelial cells in a
variable stromal background.
Common site
● Parotid gland, especially superficial lobe
● It may also occur in minor salivary glands
Clinical features
● Slow-growing
● Painless
● Firm
● Mobile salivary gland swelling
● Facial nerve involvement is usually absent in benign tumours
Morphology
Gross
● Well-circumscribed
● Lobulated
● Firm
● Grey-white cut surface
● Often surrounded by a capsule, although the capsule may be incomplete
Microscopy
● Epithelial cells forming ducts, tubules or nests
● Myoepithelial cells
● Chondromyxoid stroma
● Cartilage-like, myxoid or hyalinized areas may be present
Complications
● Local recurrence if incompletely excised
● Recurrence occurs due to incomplete capsule and tumour projections
● Rare malignant transformation into carcinoma ex pleomorphic adenoma