Digestive Pathology

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Jaundice

Back 1

A yellow discoloration of the skin and sclerae (icterus)

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Jaundice occurs when bilirubin levels

Back 2

Rise above 2.0 - 2.5 mg/dl (normal levels 0.3 - 1.2 mg/dl)

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Mechanisms of Jaundice

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1. Excessive production of bilirubin

2. Reduced hepatic uptake

3. Impaired conjugation

4. Decreased hepatocellular excretion

5. Impaired bile flow

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Congenital Unconjugated Hyperbilirubinemia

Back 4

1. Neonatal Jaundice ( decreased UDP - glucuronyltransferase activity -UGT1A1)

2. Crigler-Najjar syndrome type 1 and 2 ( complete lack of UGT1A1 (AR) v. partial defect (AD) )

3. Gilbert Syndrome ( Decreased UGT1A1)

- Usually asymptomatic; precipitated by stress

** Hemolytic Anemia causes Unconjugtated Hyperbilirubinemia as well**

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Congenital Conjugated Hyperbilirubinemia

Back 5

1. Dubin Johnson Syndrome

- Autosomal Recessive

-Defect in transport protein (excretion defect)

- Darkly pigmented liver

2. Rotor Syndrome

- Variant of Dubin Johnson

- No liver pigment

Front 6

Other Causes of Conjugated Hyperbilirubinemia

Back 6

1. Biliary Tract Obstruction: Gallstones, Cholangcarcinoma, Pancreatic/Liver Cancer, Liver Fluke

2. Biliary Tract Disease

- Primary Sclerosing Cholangitis

- Primary Biliary Cirrhosis

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Cholestasis

Back 7

1. Systemic retention of bilirubin and other solutes eliminated in bile

2. Caused by Hepatocellular Dysfunction (intrahepatic or extra hepatic)

3. Presents with Jaundice, Pruritus, Xanthomas, and elevated levels of serum alkaline phosphatase (ALP)

4. Foamy degeneration of hepatocytes and distended bile ducts/lakes

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Liver Failure

Back 8

1. Most severe consequence of liver disease

2. 80-90% of hepatic function capacity eroded

Front 9

Liver Failure: Causes

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1. Massive Hepatic Necrosis

-Fuliminant Viral Hepatitis

- Drugs and chemicals

2. Chronic Liver Disease

- Cirrhosis

3. Hepatic Dysfunction w/e overt necrosis

- Reye Syndrome (fatal childhood encephalopathy)

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Liver Failure: Clinical Features

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1. Jaundice

2. Hypoalbuminenia

3. Hyperammonemia

4. Spider Angiomas

5. Testicular Atrophy, Gynecomastia

6. Coagulopathy

7. Death within weeks to months

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Hepatic Encephalopathy

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1. Complication of acute and chronic liver failure

2. Presents with marked stupor, confusion, coma, and death

3. Neurological signs: Rigidity, hyperreflexia seizures, or asterixis (flapping tremor)

Front 12

Hepatorenal Syndrome

Back 12

The appearance of renal failure in patients with liver failure

** Improves if hepatic function is reversed**

Front 13

Cirrhosis

Back 13

1. End-stage liver damage characterized by disruption of normal liver parenchyma by bands of fibrosis and regenerative nodules of hepatocytes

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Cirrhosis: Etiology

Back 14

1. Alcohol (60-70%)

2. Chronic viral hepatitis

3. Biliary disease

4. Genetic/Metabolic disorders

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Cirrhosis: Clinical Features

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1. Asymptomatic

2. Or, Anorexia, weight loss, weakness, frank debilitation

Causes of death:

- Progressive liver failure

- Portal Hypertension

- Hepatocellular Carcinoma (Increased risk)

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Portal Hypertension

Back 16

1. Increased resistance to portal flow

2. Prehepatic, hepatic, and post hepatic causes

3. Cirrhosis (hepatic) accounts for most cases

Front 17

Portal Hypertension: Clinical Features

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1. Esophageal Varices

2. Melena

3. Splenomegaly

4. Caput Medusa

5. Ascites

6. Anorectal Varices

Front 18

Viral Hepatitis

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1. Inflammation of liver parenchyma (A-E)

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Viral Hepatitis A

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1. Benign, self-limited disease spread by fecal-oral transmission

2. Commonly acquired by travelers

3. Antibody (IgM) against HAV; immunizations

4. No chronic hepatitis

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Viral Hepatitis B

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1. Can result in

- Acute hepatitis

- Chronic hepatitis

- Cirrhosis

- Fulminant hepatitis

- HCC

2. Transmitted by IV Drug uses, unprotected sex, transfusion, dialysis,

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Viral Hepatitis C

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1. Higher rate of progression to chronic disease and cirrhosis than HBV

2. Transmission: IV-Drug Abuse, transfusion, unprotected sex

3. Persistent infection (75%); decreased HCV-RNA levels signal recovery

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Viral Hepatitis D

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1. Dependent on HBV coinfection for multiplication

2. Superinfection (existing HBV) is is more severe than coinfection (infection with HBV and HDV at same time)

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Viral Hepatitis E

Back 23

1. Self-limiting

2. Fecal-oral transmission; usually from contaminated water or undercooked seafood

3. High mortality rate among pregnant females (20%)

4. Not associated with chronic liver disease

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Viral Hepatitis: Carrier State

Back 24

1. An asymptomatic individual who can transmit an organism

2. Typically seen with HBV

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Acute Viral Hepatitis: Stages

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1. Incubation period

2. Preicteric phase

- Malaise

- Fatigability

- Nausea, Loss of appetite

- Inc. Serum Aminotransferase levels

3. Icteric Phase

- Jaundice caused by inc. serum conjugated and unconjugated bilirubin

- Dark or tea colored urine and light or clay-colored stool

4. Convalescence

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Chronic Viral Hepatitis

Back 26

1. Continuing or releasing hepatic disease for more than 6 months

2. May see elevated prothrombin time, and sometimes hyperglobulenmia/bilirubinemia, and mild elevation in ALP

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Massive Hepatic Necrosis

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1. Acute massive liver destruction

2. Causes: Viral hepatitis (50-65%), drugs and chemicals (25-30%)

3. Liver: shrunken, soft w/ wrinkled capsule

4. May present as jaundice and encephalopathy

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Alcoholic Liver Disease

Back 28

1. Most common cause of liver disease in the West

2. Three forms

- Hepatic steatosis

- Alcoholic Hepatitis

- Cirrhosis

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Hepatic Steatosis

Back 29

1. Large, yellow greasy liver

2. Cause: Increased lipid biosynthesis, impaired secretion of lipoproteins, increased peripheral catabolism of fat

3. Reversible with alcohol withdrawal

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Alcoholic Hepatitis

Back 30

1. Chemical injury (acetaldehyde damage) to hepatocytes from binge drinking

2. Swelling of hepatocytes cause Mallory Bodies (damaged cytokeratin filaments)

3. Painful hepatomegaly with AST > ALT

4, 15-20 years of ethanol abuse necessary

Front 31

Alcoholic Cirrhosis

Back 31

1. Complication and irreversible form of alcohol induced damage

2. Shrunken, firm liver with hobnail appearance

Front 32

Hemochromatosis

Back 32

1. Hereditary (AR) defect in regulation of intestinal iron absorption

2. Acquired: secondary to iron overload

3. Deposition of hemosiderin in liver, pancreas myocardium, and skin

4. Liver: brown granular pigment, stains w/ purssian blue

5. Disease of males over age 40

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Hemochromatosis: Clinical Features

Back 33

1. Hepatomegaly, abdominal pain, arrhythmias, arthritis

2. Bronze diabetes: classic triad of cirrhosis w/ hepatomegaly, skin pigmentation, and diabetes mellitus

Front 34

Wilson Disease

Back 34

1. Autosomal recessive disorder (ATP7B) associated w/ accumulation of cooper

2. Liver: Hepatitis then cirrhosis

3. Brain: deposits in basal ganglia

- Neurological manifestations (behavioral changes, dementia, chorea, parkinson)

4. Eye: Kayser-Fleischer ring

5. Increased urinary cooper and decreased serum ceruloplasmin

6. Increased risk of HCC

7. Treatment: D-pencillamine (chelates cooper)

Front 35

Alpha-Antitrypsin (AAT) Deficiency

Back 35

1. Autosomal recessive disorder associated w/ emphysema

2. PiZZ: Abnormal gene on Chromosome 14

3. ATT retained in hepatocytes as cytoplasmic globules (stain PAS positive)

4. Cirrhosis occurs in adulthood

Front 36

Reye Syndrome

Back 36

1. Characterized by fatty change of the liver and encephalopathy

2. Mainly affects children < 4

3. Develops 3-4 days after viral illness

4. Associated w/ salicylate administration

Front 37

Primary Biliary Cirrhosis

Back 37

1. Chronic cholestatic liver disease

2. Autoimmune Granulomatous destruction of intrahepatic ducts; cirrhosis occurs late

3. Generally seen in women 40-50

Front 38

Primary Biliary Cirrhosis: Clinical Features

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1. Pruritis

2. Jaundice

3. Elevated serum ALP, cholesterol, and conjugated bilirubin

4. Antimitochondrial antibodies (90%)

Front 39

Passive Congestion

Back 39

1. Seen with right-sided heart failure

2. Congestion of the centrilobular sinusoids

3. Ischemia = centrilobular necrosis

4. "Nutmeg" liver

Front 40

Hepatic Vein Thrombosis (Budd-Chari Syndrome)

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1. Thrombosis of hepatic vein leads to severe centrilobular congestion and necrosis

Front 41

Budd Chari Syndrome: Clinical Features

Back 41

1. Congestive liver damage; ascites, hepatomegaly, weight gain, and abdominal pain

2. Associated w/ Polycythemia vera, myleoproliferative disorders, pregnancy, oral contraceptives, and HCC

3. Absence of JVD

4. May cause nutmeg liver

Front 42

Benign Tumors

Back 42

1. Cavernous hemangioma (most common)-Bright Red lesion: Strawberry Mark

2. Focal nodular hyperplasia

3. Liver cell adenoma (associated with oral contraceptives) - Pictured

Front 43

Malignant Tumors

Back 43

1. Primary

- Hepatocellular carcinoma

- Angiosarcoma

- Cholonagiocarcinoma

2. Metastatic (most common malignancy)

Front 44

Hepatocellular Carcinoma (HCC)

Back 44

1. Most common primary cancer

2. HBV infection seen in over 85% of cases worldwide

3. Males 8:1, more common in blacks

4. Third to fifth decades

Front 45

HCC: Etiology

Back 45

1. HBV and HCV

2. Cirrhosis

3. Aflatoxins (Aspergillus induce p53 mutations)

Front 46

HCC: Morphology

Back 46

1. Large univocal lesion; may also be multifocal or diffusively infiltrative

2. Well-differentiated hepatocytes arranged in cords or small nests

3. Cholestasis

Front 47

HCC: Additional Features

Back 47

1. May presents as silent hepatomegaly

2. Often seen in setting of cirrhosis w/ worsening of symptoms

3. Elevated levels of Alpha-fetoprotein

4. Death from profound cachexia, GI or esophageal variceal bleeding, or liver failure w/ hepatic coma (medial survival - 7 months)

Front 48

Angiosarcoma

Back 48

1. Associated w/ polyvinyl chloride, arsenic, and Thorotrast exposure

Front 49

Cholangiocarcinoma

Back 49

1. Arise from the biliary tree

2. Incidence higher in China and associated with Opisthorchis (Clonorchis) sinensis liver fluke

Front 50

Metastatic Cancer

Back 50

1. More common than primary liver cancers

- Colon

- Breast

- Lung

- Pancreas

2. Results in multiple nodules of the liver