Hepatobiliary and Pancreatic Disorders

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Unconjugated bilirubin:

• Lipid soluble.

• End product of heme degradation.

Conjugated bilirubin:

• Unconjugated bilirubin + conjugation = conjugated bilirubin.

• Conjugated bilirubin is water soluble, stored in gall bladder, enters duodenum.

• Conjugated bilirubin converted to urobilin by intestinal bacteria.

Jaundice:

• Jaundice = increased unconjugated bilirubin or conjugated bilirubin.

Viral hepatitis:

• Fever, hepatomegaly, jaundice.

Dark urine and dark stools:

• Extravascular hemolysis.

• Increased macrophage production of unconjugated bilirubin.

Obstructive liver disease:

• Increased serum and urine conjugated bilirubin.

• Increased (alkaline phosphatase) ALP, GGT; NOTE: only ALP is elevated in bone disease.

Autoimmune hepatitis:

• Mostly in young women.

• Fever, hepatomegaly, jaundice.

• Positive ANA test.

• Anti-smooth muscle antibodies.

Neonatal hepatitis:

• Idiopathic.

• CMV, metabolism disorders.

• Giant cells.

Reye syndrome:

• Children younger than 4 years.

• Follows chickenpox or influenza infection.

• Mitochondrial damage.

• Encephalopathy hepatomegaly.

• Transaminasemia, increased bilirubin and ammonia.

Preeclampsia:

• Hypertension, proteinuria, pitting edema during 3rd trimester of pregnancy.

• HELLP syndrome; hemolytic anemia, elevated transanimases, low platelets.

Fulminant hepatic failure:

Causes:

• Viral, drugs, Reye syndrome.

Findings:

• Encephalopathy.

• Decreased transaminases; increased PT and ammonia.

Prehepatic obstruction of blood flow:

• Blood doesn't flow to liver.

• Hepatic artery thrombosis; transplant rejection; vasculitis.

• Portal vein thrombosis; pylephlebitis, polycythemia vera, carcinoma.

Intrahepatic obstruction of blood flow:

• No sinusoidal blood flow; cirrhosis.

• Centrilobular hemorrhagic necrosis; LHF, RHF.

• Nutmeg liver.

• Pain, increased transaminases.

Peliosis hepatic:

• Sinusoidal dilation.

• Steroids, infections.

Posthepatic obstruction of blood flow:

• Blood doesn't flow out of liver.

• Hepatic vein thrombosis; veno-occlusive disease.

Causes:

• Polycythemia vera, oral contraceptive pills, hepatocellular carcinoma.

Findings:

• Enlarged, painful liver, portal hypertension, ascites, splenomegaly.

• Increased transaminases, PT.

Alcohol hepatitis:

• Acetaldehyde damage to hepatocytes.

• Fatty change; Mallory bodies, perivenular fibrosis.

• Enlarged, painful liver, fever, leukocytosis, ascites, hepatic encephalopathy.

Obstructive (cholestatic) liver disease:

Intrahepatic Obstructive (cholestatic) liver disease:

• Blockage of intrahepatic bile ducts.

• Drugs, neonatal hepatitis, pregnancy.

Extrahepatic Obstructive (cholestatic) liver disease:

• Blockage of common bile duct.

• Stones, primary sclerosing pericholangitis, extrahepatic biliary atresia, carcinoma head of pancreas.

• Enlarged, green liver.

• Jaundice, malabsorption, cholesterol deposits in skin, light-colored stools.

• Increased conjugated bilirubin, bilirubinuria, increased ALP, GGT.

Liver cirrhosis:

• Liver fibrosis + formation of regenerative nodules.

• Compressed hepatic arteries and veins.

Causes:

• Alcohol, viral, autoimmune, metabolic disease.

Complications:

Hepatic failure:

• Hypoalbuminemia, hepatic encephalopathy, portal hypertension, ascites, hepatorenal syndrome, hyperestrinism in males.

Primary biliary cirrhosis:

• Autoimmune disorder.

• Destruction of bile ducts and portal triads.

• Pruritis, hepatomegaly, jaundice.

• Antimicrobial antibodies, increased IgM.

Hereditary hemochromatosis:

• AR disease.

• Unrestricted reabsorption of iron in SI.

• Iron deposits in organs.

• Bronze diabetes.

• Type I diabetes mellitus.

• Malabsorption.

• Cardiomyopathy, joint degeneration.

• Increased iron, ferritin, TIBC.

Wilson's disease:

• AR disorder.

• Decreased ceruplasmin synthesis.

• Increased serum copper; increased copper in urine.

• Kayser-Fleischer ring.

Alpha-antitrypsin deficiency:

• AD disease.

• Accumulation of Alpha-antitrypsin in hepatocytes causing liver damage.

• Hepatitis.

Laboratory confirmation of cirrhosis:

• Increased BUN, hypoglycemia, respiratory alkalosis, lactic acidosis, increased PT, hypocalcemia.

Liver tumors: Benign:

Cavernous hemangioma:

• Most common.

Liver cell adenoma:

• Women of child-bearing age.

Liver tumors: Malignant:

• Metastasis: most common cancer.

Heptocellular carcinoma:

• Most common.

• HBV, HCV.

• Focal, muitifocal, infiltrating cancer.

• Portal and hepatic vein invasion.

• Fever, enlargement of liver, ascites.

• Increased AFP; ectopic production of erythropoietin and insulin-like factor.

• Spreads to lungs.

Gallbladder and biliary tract disease:

Choledochal cyst:

• Children younger than 10.

• Pain and jaundice.

Caroli disease:

• AR disease.

• Dilation of intrahepatic bile ducts.

Cholangiocarcinoma:

• Most common.

• Obstructive jaundice, palpable gallbladder (Courvoisier's sign).

Gallstones (cholelithiasis):

• Most are cholesterol stones.

• Supersaturation of bile with cholesterol.

• Female, fat, forties; oral contraceptives, rapid weight loss.

Complications:

• Cholecystitis, common bile duct destruction, gallbladder cancer, acute pancreatitis.

Acute cholecystitis:

• Obstruction of cystic duct by stone.

• AIDS.

• Fever, nausea, vomiting; colicky pain.

• Jaundice.

• Ultrasound and radionuclide scan.

Chronic cholecystitis:

• Cholelithiasis.

• Pain; recurrent epigastric distress, belching, bloating.

Cholesterolosis:

• Excess cholesterol in bile.

Gallbladder adenocarcinoma:

• Elderly women; poor prognosis.

Pancreatic disorders:

Acute pancreatitis:

• Alcohol, gallstones.

• Activated pancreatic proenzymes.

• Trypsin plays a role in activating enzymes.

• Fever, nausea, vomiting, midepigastric pain radiating to back, shock, hypoxemia, Grey-Turner's sign (flank hemorrhage), Cullen's sign (periumbilical hemorrhage), tetany.

• Increased pancreatic amylase, lipase; neutrophilic leukocytosis, hypocalcemia, hyperglycemia.

• Complications: pancreatic pseudocyst, ARDS, pancreatic abscess, DIC.

Chronic pancreatitis:

• Idiopathic.

• Alcohol, Cystic Fibrosis, malnutrition.

• Repeated attacks of acute pancreatitis, calcification of ducts.

• Pain, malabsorption, type 1 diabetes mellitus, pancreatic pseudocyst.

• Increased lipase, amylase.

Exocrine pancreatic cancer:

• Smoking, pancreatiris.

• Activated K-RAS gene; mutant TP16 and TP53 genes.

• Jaundice, epigastric pain, weight loss, light-colored stools.

• Increased CA19-9.

• Poor prognosis.

Additional Reading:

Basic Pathology

1. Cell Injury
2. Inflammation and Repair
3. Immunopathology
4. Water, Electrolyte, Acid-Base, Hemodynamic Disorders
5. Genetic and Developmental Disorders
6. Environmental Pathology
7. Nutritional Disorders
8. Neoplasia
9. Vascular Disorders
10. Heart Disorders
11. Red Blood Cell Disorders
12. White Blood Cell Disorders
13. Lymphoid Tissue Disorders
14. Hemostasis Disorders
15. Blood Banking and Transfusion Disorders
16. Upper and Lower Respiratory Disorders
17. Gastrointestinal Disorders
18. Hepatobiliary and Pancreatic Disorders
19. Kidney Disorders
20. Lower Urinary Tract and Male Reproductive Disorders
21. Female Reproductive and Breast Disorders
22. Endocrine Disorders
23. Musculoskeletal Disorders
24. Skin Disorders
25. Nervous System Disorders
26. Notes on Tissue Regeneration
27. A Table of Bleeding Disorders
28. FAQ on Structure and Function of Red Blood Cells
29. FAQ on Components of Blood
30. Notes on Hemostatic Mechanisms
31. What is Fever?
32. What is Edema?
33. FAQ on Blood Pressure
34. FAQ on principles of fluid and flow dynamics of Blood
35. Causes of Thrombocytopenia
36. Squamous cell carcinoma of head and neck mucosa
37. Four tumors which never metastasize to the brain
38. What is caustic injury?
39. What causes Peripheral Edema?

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