Liver Pathologies Flashcards
Cirrhosis:
What two things disrupt normal liver architecture?
Increased risk for HCC?
Etiologies (6)
End stage liver damage characterized by disruption of normal hepatic parenchyma by diffuse bridging fibrosis bands (by TGF-beta from stellate cells) and regenerative nodules
Inc. risk for HCC
Etiologies:
- alcohol (60-70% of cases in US)
- nonalcoholic steatohepatitis (NASH)
- AI hepatitis
- Chronic viral hepatitis
- Biliary disease
- Genetic/metabolic disorders
Clinical features of cirrhosis
-
Portal Hypertension
- What is portal HTN?
- Etiologies? (3)
- Effects?
-
Decreased detox
- Consequences?
-
Decreased protein synthesis
- Consequences?
- Portal HTN = Inc. pressure in portal venous system
- Etiologies:
- cirrhosis (most common cause in Western countries)
- vascular obstruction (e.g., portal vein thrombosis, Budd-Chiari syndrome)
- schistosomiasis (“snail disease”)
- Etiologies:
- Decreased detox
- Mental status changes, asterixis (flapping tremor), eventual coma (due to inc. serum ammonia)
- Gynecomastia, spider angioma, palmar erythema due to hyperestrinism
- Jaundice
- Decreased protein synthesis
- Hypoalbuminemia w edema
- Coagulopathy due to dec. synthesis of clotting factors; degree of deficiency followed by PT
Serum markers of liver pathology:
Enzymes released in liver damage (4)
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Alkaline phosphatase (AP)
Gamma-glutamyl transpeptidase (GGT)
AST, ALT findings in:
- Most liver disease
- Alcoholic liver disease
- Most liver disease: ALT > AST
- Alcoholic liver disease: AST > ALT
** AST > ALT in nonalcoholic liver disease suggests progression to advanced fibrosis or cirrhosis
Alkaline phosphatase levels are increased in which conditions (3)
Cholestasis (e.g. biliary obstruction)
Infiltrative disorders
Bone disease
Gamma-glutamyl transpeptidase (GGT) levels are increased in which conditions?
Inc. in various liver and biliary diseases (just as ALP can) but NOT in bone disease
Associated with alcohol use
Functional liver markers (4)
-
Bilirubin:
- Inc. in various liver diseases (e.g., biliary obstruction, alcoholic or viral hepatitis, cirrhosis), hemolysis
-
Albumin:
- Dec. in advanced liver disease
-
Prothrombin:
- Inc. in advanced liver disease (dec. production of clotting factors)
-
Platelets:
- Dec. in advanced liver disease (dec. thrombopoietin, liver sequestration) and portal HTN (splenomegaly/splenic sequestration)
Reye Syndrome
Findings: (6)
Associated with:
Rare, often fatal childhood liver failure + hepatic encephalopathy post-viral illness (esp. VZV and influenza B) who take aspirin
Findings:
- Mitochondrial abnormalities
- Fatty liver (microvesicular fatty change)
- Hypoglycemia
- Vomiting
- Hepatomegaly
- Coma
Avoid aspirin in children with Reye Syndrome (except in those with Kawasaki disease)
Aspirin metabolites dec. beta oxidation by reversible inhibition of mitochondrial enzymes
Kawasaki disease causes inflammation in medium-sized arteries, particularly affecting children
Alcoholic liver disease: progression
Hepatic steatosis –> Alcoholic hepatitis –> Alcoholic cirrhosis
Hepatic steatosis:
- Macrovesicular fatty change
- May be reversible with alcohol cessation
Alcoholic hepatitis (“make a toAST w alcohol: AST > ALT, ratio usually > 2:1, painful hepatomegaly):
- Sustained, long-term consumption –> chemical injury to hepatocytes
- Acetaldehyde (metabolite of alcohol) mediates damage
- Swollen, necrotic hepatocytes + neutrophilic infiltration
- Mallory bodies (damaged cytokeratin filaments)
Alcoholic cirrhosis:
- Final/irreversible form
- Micronodular, irregularly shrunken liver + “hobnail” appearance
- Sclerosis around central vein (zone III)
- Manifestations of chronic liver disease (e.g., jaundice, hypoalbuminemia)
Non-alcoholic fatty liver disease
Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol
- Associated with obesity –> fatty infiltration of hepatocytes –> cellular “ballooning” –> necrosis
- May cause cirrhosis + HCC
- ALT > AST (Lipids)
Hepatic encephalopathy
Description:
Spectrum range:
Triggers:
Tx:
Cirrhosis –> portosystemic shunts –> dec. ammonia metabolism –> neuropsychiatric dysfunction
Spectrum from disorientation/asterixis (flapping tremor) (mild) to coma (severe)
Triggers:
- Inc. NH3 production and absorption (due to dietary protein, GI bleed, constipation, finfection)
- Dec. NH3 removal (due to renal failure, diuretics, bypassed hepatic blood flow post-TIPS)
Treatment:
-
Lactulose (inc. NH4+ generation) - FIRST LINE
- Lactulose inhibits intestinal ammonia production –> conversion of lactulose to lactic acid and acetic acid results in acidification of the gut lumen. –> favors conversion of ammonia (NH3) to ammonium (NH4+);
- owing to the resultant relative impermeability of the membrane, the NH4+ ions are not easily absorbed, thereby remaining trapped in the colonic lumen, and there is a reduction in plasma NH3.
- Lactulose also works as a cathartic, reducing colonic bacterial load.
- ANTIBIOTICS: Rifaximin or Neomycin (dec. NH4+ producing gut bacteria) - SECOND LINE
Hepatocellular Carcinoma/Hepatoma
Association/RIsk Factors:
Findings:
Tumor marker:
Most common primary malignant tumor of liver
Association/Risk Factors:
- Associated with HBV (+/- cirrhosis): HCC may develop in patients with hep B before cirrhosis occurs (this is not the case in hep C)
- Cirrhosis (e.g., alcohol, non-alcoholic fatty liver disease, hemochromatosis, Wilson disease, A1AT deficiency)
- Aflatoxins derived from Aspergillus (induce p53 mutations)
May lead to Budd-Chiari syndrome
Findings: jaundice, tender hepatomegaly, ascites, polycythemia, anorexia
Tumor marker: alpha-fetoprotein (AFP) -> confirm with biopsy
Hepatocellular Adenoma
Rare, benign hepatic tumor highly associated w OCPS/anabolic steroid use
May regress spontaneously or rupture (abdominal pain + shock)
Cavernous hemangioma
Most common, benign liver tumor (proliferation of blood vessels)
DO NOT BIOPSY!
Biopsy C/I b/c of risk of hemorrhage
Hemochromatosis
- Recessive mutations in HFE gene (C282Y > H63D, xsome 6) –> defect in IRON ABSORPTION
- Result: organ damage due to IRON OVERLOAD: abnormal iron sensing and inc. intestinal absorption
- Tissue damage mediated by generation of free radicals
- Findings:
- Inc. ferritin
- Inc. iron
- Dec. TIBC –> Inc. transferrin saturation
- Iron accumulates, esp. in liver, pancreas, skin, heart, pituitary, joints
- Hemosiderin (iron) can be identified on liver MRI or biopsy with Prussian blue stain
- Differentiate from lipofuscin (brown pigment that is a by-product from the turnover of peroxidized lipids)
