Ultimate Pathology Exam Guide

• May occur at any level, but is more frequent in the small intestine.
• Can present at any age (birth, infancy, childhood, adulthood).
• Clinical Triad: Abdominal distension (+/- pain), followed by vomiting, then constipation.
• Location of Obstruction:
  • The Lumen: Tumor, Foreign body, Intussusception.
  • The Wall: Chronic inflammation, Fibrosis, Hematoma.
  • Extramural: Hernias, Adhesion, Volvulus.
• Epidemiology: Tumors and infarction account for 10-15% of small bowel obstruction. Hernias, intestinal adhesions, intussusception, and volvulus account for 80% of cases.

• Mechanical Obstruction:
  • Congenital: Strictures, atresias, bands, imperforate anus, meconium in Cystic Fibrosis (CF).
  • Infants: Hernias, Intussusception.
  • Adults: Hernias, adhesions, tumors, inflammatory strictures, obstructive gallstones, fecoliths, foreign bodies, volvulus.
• Functional Obstruction:
  • Paralytic ileus: Lack of peristalsis associated with stagnation. Causes: Electrolyte imbalance, neural injury, reflex atony secondary to peritonitis & abdominal surgery.
  • Bowel infarction.
  • Myopathies & Neuropathies: e.g., Hirschsprung’s disease.

• Hernias: Weakness in the peritoneal wall. Sites: Inguinal, femoral, umbilicus, surgical scars.
  • Incarceration: Permanent trapping due to venous stasis & edema.
  • Strangulation: Arterial & venous supply compromised leading to infarction or gangrene.
• Intestinal Adhesions: Fibrous bridges creating closed loops (internal hernias). Causes: Surgical procedures, Infection, Endometriosis.
• Intussusception: Segment telescoped into distal segment.
  • Intussusceptum: The trapped bowel segment.
  • Intussuscipiens: The segment that envelops it.
  • Infants: Unknown pathogenesis, associated with active peristalsis.
  • Adults: Intraluminal tumor acts as a point of traction. Leads to obstruction & infarction (trapping mesenteric vessels).
• Volvulus: Complete twisting of bowel loop about its mesenteric base. Mostly affects sigmoid colon & cecum (more mobile segments). Causes venous/arterial constriction leading to infarction. May also be caused by colon malrotation & peritoneal bands.

• Benign Tumors: Stromal tumors, Lipomas, Hyperplastic & adenomatous polyps.
• Malignant Tumors: Adenocarcinoma, Carcinoid tumors, Lymphoma, Sarcoma.
• Small Intestinal Adenocarcinoma:
  • Mostly arise in the duodenum, including ampulla of Vater.
  • Gross: Polypoid fungating tumor growing in a napkin-ring encircling pattern.
  • Presentation: Usually asymptomatic early. Symptoms appear late (pain, nausea, weight loss) when penetrated bowel wall.
  • Prognosis: 5-year survival with wide en bloc excision is 70%.
• Carcinoid Tumors:
  • Low-grade malignant tumors originating from neuroendocrine cells (epithelial stem cell origin).
  • Capable of producing bioactive compounds causing syndromes (e.g., gastrinoma, insulinoma).
  • Prognosis: 5-year survival with wide en bloc excision is 70%.

• Colonic tumors are much more common than small intestinal tumors.
• Most are of epithelial origin. Majority are benign, but Colonic Cancer is a major cause of morbidity/mortality.
• Clinical Presentation: Asymptomatic (incidental), Blood per rectum, Anemia, Bowel obstruction.

• Polyp: Tumorous mass protruding into the lumen (pedunculated/with stalk or sessile/flat).
• Non-neoplastic (90%): Hyperplastic, Hamartomatous, Inflammatory. Formed due to abnormal mucosal maturation.
• Neoplastic (Pre-cancerous): Formed due to epithelial proliferation and dysplasia.
  • Tubular Adenoma: >85% of adenomas (Most common neoplastic polyp). Mostly in distal colon (50% in rectosigmoid). Usually small (few mm - 2 cm) & pedunculated. Variable dysplasia to Carcinoma in Situ (CIS). Invasive carcinoma is rare (1-3%). Cured by polypectomy.
  • Villous Adenoma: 10%. Rectosigmoid & rectum (75%). Sessile (broad based), large (1-10 cm, most are 1-3cm). Forms finger-like projections (>50% villous). Endoscopic removal is often not possible. High risk: Carcinoma in situ 10%, Invasive carcinoma 30%.
  • Tubulovillous Adenoma: 5-10%. Mixture of both (20-50% villous). 20-30% are <40 yrs; 50% after 60. Clinical: occult bleeding, anemia, hypoproteinemia, hypokalemia.

• Familial Adenomatous Polyposis (FAP):
  • Autosomal dominant trait.
  • Requires at least 100 polyps for diagnosis (average 1000). Mostly tubular.
  • Genetic defect: APC gene (Tumor Suppressor Gene deletion) on Chromosome 5q21.
  • Risk: 100% risk of colon adenocarcinoma by age 30.
  • Not present at birth, appears in childhood/second decade. Treatment: Prophylactic colectomy in midlife.
• Gardner’s syndrome: Variant of FAP. Associated with multiple osteomas, epidermal cysts, fibromatosis, thyroid Ca.
• Turcot’s syndrome: Variant of FAP. Associated with CNS tumors (gliomas).

• Epidemiology: More than 98% of colonic malignancies. Peak incidence: 60-70 years. (<20% before age 50 unless patient has FAP or Ulcerative Colitis). Equally affect male & female.
• Dietary Risk Factors:
  • Low unabsorbable vegetable fiber content (causes constipation).
  • High refined carbohydrate content (high calories = obesity).
  • High fat content (refined sugar = potential carcinogen).
  • Low protective micronutrients (Vitamins A, C & E).
• "Multi-hit" Carcinogenesis Concept:
  1. First hit: Mutation of APC & Mismatch Repair genes.
  2. Second hit: Methylation abnormalities/inactivation of normal alleles.
  3. Protooncogene: K-ras mutation at 12p12 (leads to tubular adenoma formation).
  4. Loss of Suppressors: DCC at 18q21 and p53 at 17p13 (leads to growth & invasion).
• Morphology & Clinical Presentation:
  • Proximal / Right Colon (35%): Fungating polypoid tumors. Presentation: Fatigue, weakness, iron-deficiency anemia.
  • Distal / Left Colon (55%): Annular encircling (napkin-ring) causing lumen narrowing. Presentation: Occult bleeding, change in bowel habit.
• Intestinal Lymphoma: GIT is the most common extranodal location. Associated with Helicobacter Pylori (H. Pylori), Celiac disease, AIDS. MALTomas: low-grade B-cell lymphoma.

Modified Dukes’ (Astler-Coller) Staging

• Affects 10-20% men, 30-40% women.
• Types:
  1. Cholesterol stones (80%): Crystalline cholesterol monohydrate.
  2. Pigmented stones (20%): Bilirubin calcium salts.
• Pathogenesis (3 Conditions): 1. Supersaturation (hyperlipidemia - when cholesterol exceeds solubilizing capacity), 2. Nucleation (stasis - kinetically favorable), 3. Time for crystals to aggregate into stones.
• Risk Factors for Cholesterol Stones (6F's): Familial, Forty & above, Female sex hormones, Fatty (obesity/hyperlipidemia), Flatulence (malabsorption/intestinal disease), Fertile (multiparous).
• Estrogen (OCPs, pregnancy) increases hepatic cholesterol synthesis/uptake, predisposing to stones.
• Risk Factors for Pigmented Stones: Asian demography, Chronic hemolytic syndrome, Biliary infection, GI disorders (Crohn's, CF).
• Complications: Empyema, perforation, fistula (Gallstone Ileus) where a large stone erodes into small bowel. Small stones are more dangerous as they enter ducts causing obstruction.

• Acute Calculous Cholecystitis: Most common complication of gallstones. Obstruction of neck/cystic duct (90% have stones). Gallbladder is enlarged (2-3 fold) with green-black discoloration due to subserosal hemorrhage.
• Acute Acalculous Cholecystitis: (5-12%). No stones. Occurs in seriously ill patients (postoperative, severe trauma, burns, sepsis, dehydration).
• Pathogenesis (5 Factors):
  1. Phospholipase hydrolyzes lecithin to toxic Lysolecithin.
  2. Disruption of protective glycoprotein mucosal layer.
  3. Prostaglandins cause mural inflammation.
  4. Increased pressure compromises blood flow.
  5. Bacterial contamination (late).
• Morphology: Empyema (pure pus exudate). Gangrenous cholecystitis (severe case, green-black necrotic organ).
• Chronic Cholecystitis: Associated with gallstones. Submucosal/subserosal fibrosis. Mural lymphocytes. Rokitansky-Aschoff sinuses (irregular gland-like mucosal pockets extending deep into muscle layer).
• Complications of Chronic Cholecystitis:
  1. Bacterial super infection (cholangitis, sepsis).
  2. Perforation & local abscess formation.
  3. Rupture with diffuse peritonitis.
  4. Biliary-enteric fistula (Gallstone ileus).
  5. Aggravation of preexisting medical disease.

• Choledocholithiasis: Stones within biliary tree.
• Cholangitis: Bacterial/parasitic infection of normally sterile bile duct wall. Enter via Sphincter of Oddi (Ascending).
  • Bacteria: E. Coli, Klebsiella, Clostridium.
  • Parasites: Fasciola hepatica, Clonorchis sinensis, Schistosomiasis, Cryptosporidiosis (AIDS).
• Suppurative Cholangitis: Purulent bile distends ducts with risk of liver abscess. Emergent because sepsis (not cholestasis) is the dominant risk.

• Biliary Atresia: Destruction or absence of extrahepatic bile ducts. Infant presents with neonatal cholestasis (1/3 of cases). Single most frequent cause of infant liver death. May be an acquired inflammatory disorder of unknown cause. Biopsy shows bile duct proliferation, portal tract edema, and cholestasis. Leads to periportal fibrosis & cirrhosis within 3-6 months.
• Carcinoma of Gallbladder: 5th most common GI cancer. Females > Males (7th decade). Gallstones present in 60-90% (repeated trauma leads to carcinoma). Mostly adenocarcinoma (minority are squamous cell 5% or carcinoid).
  • Growth Patterns: 1) Infiltrative pattern (diffuse thickening/induration). 2) Exophytic pattern (irregular cauliflower mass).
• Cholangiocarcinoma: Carcinoma of extrahepatic bile duct. Males > Females. Extremely insidious, producing painless, progressive deep jaundice. Risk factors: Fluke infection, Primary Sclerosing Cholangitis (PSC), Inflammatory Bowel Disease (IBD).
  • Clinically: Weight loss, hepatomegaly (50%), distended gallbladder (25%).
  • Labs: High ALP, aminotransaminase, Bile stained urine, Prolonged prothrombin time.

• Acute Pancreatitis: Inflammation almost always associated with acinar cell injury.
  • Etiologies:
    1. Metabolic: Alcohol, hyperlipoproteinemia, hypercalcemia, drugs (e.g., thiazides), genetic.
    2. Mechanical: Gallstones, traumatic/perioperative injury.
  • Pathogenesis: Trypsin has a major role. It activates proenzymes (proelastase, prophospholipase), converts prekallikrein to kallikrein, and activates Hageman factor.
  • Death due to: 1) Shock, 2) Secondary abdominal sepsis, 3) Adult Respiratory Distress Syndrome (ARDS).
• Chronic Pancreatitis: Repeated bouts of inflammation, loss of parenchyma, replacement by fibrous tissue.
  • Mostly middle-aged alcoholic men or due to biliary tract disease. (No apparent cause in 50%).
  • Pathogenesis: Protein hypersecretion from acinar cells -> Precipitation forming ductal plugs.
  • Pathology: Hard organ, dilated ducts, calcified concretions, extensive exocrine atrophy, Pseudocysts.
  • Complications: Pancreatic insufficiency & Diabetes Mellitus.

• Cystic Fibrosis (CF): Gene located on Chromosome 7.
• Pancreatic pathology (85%): Mucus accumulation, duct dilation/plugging, exocrine gland atrophy.
• Islets of Langerhans are usually spared.
• Ducts convert to cysts separated by fibrous stroma (Fibrocystic disease of pancreas).
• Squamous metaplasia of duct lining. Leads to Malabsorption syndrome (particularly fat), Meconium ileus (GIT), pulmonary problems.
• Pancreatic Carcinoma: 5th most frequent cause of cancer death. Peak incidence 60-80 years. Cause unknown but more frequent in smokers.
  • Location: Head (60%), Body (15%), Tail (5%), Diffuse (20%).
  • Morphology: Grossly gritty, gray hard masses. Usually a single tumor. Vast majority are adenocarcinomas with poorly formed glands and densely fibrous stroma.
  • Head carcinomas invade the ampullary region causing obstructive jaundice. Body & tail carcinomas remain silent longer.
  • Metastasis: Extends to retroperitoneal spaces, nerves, lungs, and bone.
  • Trousseau’s syndrome: Migratory thrombophlebitis associated with pancreatic cancer.

• Normal Liver: Weight is 1200-1600 g. Smooth brown surface.
  • Functions: Maintaining metabolic homeostasis (Lipid/carbohydrate - glucose; Protein synthesis - albumin/coagulation factors; Detoxification; Conjugation of bilirubin; Storage of glycogen, vitamins, minerals).
• Histology (Lobules vs Acini):
  • Portal Triads: Contain Bile duct, Hepatic artery, Portal vein branch. Surrounded by type I & III collagen.
  • Zones: Zone 1 (Periportal), Zone 2 (Mid-zonal), Zone 3 (Centrilobular / Central vein). Blood flows from portal triad to central vein.
• Histologic Patterns of Hepatic Injury:
  • Inflammation: acute/chronic, portal/lobular.
  • Degeneration: ballooning, foamy, steatosis.
  • Necrosis: Coagulative/lytic, Apoptotic (Councilman bodies). Types: centrilobular, focal, piece-meal, bridging, submassive, massive.
  • Fibrosis: Portal, central, bridging.

• Hepatitis Causes: Hepatotropic viruses, EBV, CMV, Yellow fever, Autoimmune, Drugs/toxins.
• Hepatitis A Virus (HAV): Benign, self-limited. Incubation 3-6 weeks. Fecal-oral route. Shed in stool 2-3 weeks before & 1 week after jaundice. Associated with poor hygiene and ingestion of steamed shellfish.
• Infection Outcomes:
  1. Acute Asymptomatic: Elevated transaminases, HAV/HBV mostly in childhood.
  2. Acute Symptomatic: Incubation -> preicteric phase -> icteric phase -> convalescence.
  3. Fulminant Hepatic Failure: Occur with HBV and HAV.
  4. Chronic Hepatitis: Disease for > 6 months.
  5. Carrier State: Chronically infected with no or subclinical evidence of liver disease.

• Major Hepatic Diseases:
  • Primary: Viral hepatitis, alcoholic, NAFLD, Cirrhosis, HCC.
  • Secondary: Cardiac disease, disseminated cancer, extrahepatic infections.
• Signs of Liver Failure: Jaundice, pruritus, Hepatic encephalopathy, easy bleeding/bruising, spider angiomata.
• Cirrhosis Complications: 40% are asymptomatic until advanced.
  • Portal Hypertension Signs: Gastroesophageal varices, ascites, edema, splenomegaly, caput medusae.
  • Hyperestrogenemia: Due to impaired estrogen metabolism in males, leading to palmar erythema, spider angiomas, hypogonadism, and gynecomastia.
• Cirrhosis Pathophysiology: Irreversible end-stage. Fibrosis (excess collagen type I/III by hepatic stellate cells) and regeneration (ductular reaction).
• 3 Histologic Features of Cirrhosis:
  1. Disruption of entire liver architecture.
  2. Bridging fibrous septa. (Masson trichrome stain highlights these septa).
  3. Parenchymal regenerative nodules.

• Cholestasis: Obstruction of bile channels or defects in hepatocyte bile secretion.
  • Clinical Features: Jaundice, Pruritus, Skin xanthomas (focal cholesterol accumulation), and intestinal malabsorption with deficiencies of fat-soluble vitamins (A, D, K).
  • Labs: Elevated Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transpeptidase (GGT).
• Neonatal Cholestasis: Prolonged conjugated hyperbilirubinemia in neonates. Main causes: Cholangiopathies (Biliary Atresia) and Neonatal hepatitis.
• Primary Sclerosing Cholangitis (PSC): Inflammation and obliterative fibrosis of intra/extrahepatic bile ducts. Classic finding: "Onion skin" fibrosis around affected bile ducts.

• Bile Composition: 95% Water, 5% Solute. Solute is 61% Bile acids, 12% Fatty acids, 9% Cholesterol, 7% Proteins, 3% Bilirubin.
• Metabolism: Heme -> Biliverdin (via Heme oxygenase) -> Unconjugated Bilirubin (via Biliverdin reductase) -> Conjugated in liver via UDP Glucuronyl Transferase -> Excreted to gut -> Urobilinogen.
• Jaundice (Icterus): Yellowish discoloration due to systemic retention of Bilirubin (> 2 mg/dl).
• 5 Mechanisms of Jaundice:
  1. Excessive production (Hemolysis).
  2. Reduced hepatocellular uptake.
  3. Impaired conjugation.
  4. Decreased hepatocellular excretion.
  5. Impaired bile flow.
• Kernicterus: Accumulation of unconjugated bilirubin in the brain (occurs in neonates).

• 11 Main Causes:
1. Viral hepatitis.
2. Alcoholic liver disease.
3. Biliary diseases.
4. Genetic hemochromatosis.
5. Wilson’s disease.
6. Alpha-1 antitrypsin deficiency.
7. Drugs (methyldopa, acetaminophen).
8. Syphilis.
9. Galactosemia, tyrosinosis.
10. Cardiac cirrhosis.
11. Cryptogenic cirrhosis.

• Tests of Hepatocyte Integrity: AST (Aspartate Aminotransferase / SGOT), ALT (Alanine Aminotransferase / SGPT), LDH.
• Tests of Biliary Excretory Function: Serum Bilirubin, Alkaline Phosphatase (ALP), Gamma-Glutamyl Transpeptidase (GGT).
• Tests of Hepatocyte Function (Synthesis): Albumin, Prothrombin Time (PT), Ammonia.
• Portal Hypertension Complications (Splenomegaly): Congestive splenomegaly leads to Hypersplenism (removal of excessive amounts of formed blood elements), causing: Anemia, Leukopenia, and Thrombocytopenia.

• Most Common Hepatic Neoplasm: Metastatic Tumors (most commonly from colon, lung, and breast).
• Liver Cell Adenoma:
  • Mostly in young women with history of Oral Contraceptive Pills (OCP) use.
  • Well-demarcated yellow-tan, bile-stained nodule. Cells resemble normal hepatocytes with minimal pleomorphism.
  • Clinical Significance: 1) Misdiagnosed as Hepatocellular Carcinoma. 2) May rupture & cause serious intra-abdominal hemorrhage.
  • May regress on discontinuance of OCPs.
• Primary Hepatic Carcinoma (Hepatocellular Carcinoma - HCC):
  • Asymptomatic hepatomegaly. In cirrhotics: Rapid increase in liver size, appearance of bloody ascites, fever & pain.
  • Tumor Marker: Alpha-fetoprotein (AFP). Levels >1000 ng/ml are highly suggestive of HCC.
  • Treatment: Complete surgical resection.
  • Prognosis: Grim. Death within 6 months - 1 year due to Cachexia, GI bleeding, Liver failure, or Tumor rupture.
• Cholangiocarcinoma:
  • Klatskin tumor: Present at the junction of hepatic & common bile ducts.
  • Histology: Usually well-differentiated, forming glands/tubules with desmoplastic stroma.
  • Bile pigment is NOT present. May mimic metastatic adenocarcinoma.