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Flashcards in Liver Pathologies Deck (24)
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1
Q

Cirrhosis:

What two things disrupt normal liver architecture?

Increased risk for HCC?

Etiologies (6)

A

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:

  1. alcohol (60-70% of cases in US)
  2. nonalcoholic steatohepatitis (NASH)
  3. AI hepatitis
  4. Chronic viral hepatitis
  5. Biliary disease
  6. Genetic/metabolic disorders
2
Q

Clinical features of cirrhosis

  1. Portal Hypertension
    1. What is portal HTN?
    2. Etiologies? (3)
    3. Effects?
  2. Decreased detox
    1. Consequences?
  3. Decreased protein synthesis
    1. Consequences?
A
  1. Portal HTN = Inc. pressure in portal venous system
    1. Etiologies:
      1. cirrhosis (most common cause in Western countries)
      2. vascular obstruction (e.g., portal vein thrombosis, Budd-Chiari syndrome)
      3. schistosomiasis (“snail disease”)
  2. Decreased detox
    1. Mental status changes, asterixis (flapping tremor), eventual coma (due to inc. serum ammonia)
    2. Gynecomastia, spider angioma, palmar erythema due to hyperestrinism
    3. Jaundice
  3. Decreased protein synthesis
    1. Hypoalbuminemia w edema
    2. Coagulopathy due to dec. synthesis of clotting factors; degree of deficiency followed by PT
3
Q

Serum markers of liver pathology:

Enzymes released in liver damage (4)

A

Aspartate aminotransferase (AST)

Alanine aminotransferase (ALT)

Alkaline phosphatase (AP)

Gamma-glutamyl transpeptidase (GGT)

4
Q

AST, ALT findings in:

  1. Most liver disease
  2. Alcoholic liver disease
A
  1. Most liver disease: ALT > AST
  2. Alcoholic liver disease: AST > ALT

** AST > ALT in nonalcoholic liver disease suggests progression to advanced fibrosis or cirrhosis

5
Q

Alkaline phosphatase levels are increased in which conditions (3)

A

Cholestasis (e.g. biliary obstruction)

Infiltrative disorders

Bone disease

6
Q

Gamma-glutamyl transpeptidase (GGT) levels are increased in which conditions?

A

Inc. in various liver and biliary diseases (just as ALP can) but NOT in bone disease

Associated with alcohol use

7
Q

Functional liver markers (4)

A
  1. Bilirubin:
    1. Inc. in various liver diseases (e.g., biliary obstruction, alcoholic or viral hepatitis, cirrhosis), hemolysis
  2. Albumin:
    1. Dec. in advanced liver disease
  3. Prothrombin:
    1. Inc. in advanced liver disease (dec. production of clotting factors)
  4. Platelets:
    1. Dec. in advanced liver disease (dec. thrombopoietin, liver sequestration) and portal HTN (splenomegaly/splenic sequestration)
8
Q

Reye Syndrome

Findings: (6)

Associated with:

A

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
9
Q

Avoid aspirin in children with Reye Syndrome (except in those with Kawasaki disease)

A

Aspirin metabolites dec. beta oxidation by reversible inhibition of mitochondrial enzymes

Kawasaki disease causes inflammation in medium-sized arteries, particularly affecting children

10
Q

Alcoholic liver disease: progression

A

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)
11
Q

Non-alcoholic fatty liver disease

A

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)
12
Q

Hepatic encephalopathy

Description:

Spectrum range:

Triggers:

Tx:

A

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
13
Q

Hepatocellular Carcinoma/Hepatoma

Association/RIsk Factors:

Findings:

Tumor marker:

A

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

14
Q

Hepatocellular Adenoma

A

Rare, benign hepatic tumor highly associated w OCPS/anabolic steroid use

May regress spontaneously or rupture (abdominal pain + shock)

15
Q

Cavernous hemangioma

A

Most common, benign liver tumor (proliferation of blood vessels)

DO NOT BIOPSY!

Biopsy C/I b/c of risk of hemorrhage

16
Q

Angiosarcoma

A

Malignant tumor of endothelial origin

Associated with exposure to arsenic, vinyl chloride

17
Q

Budd-Chiari Syndrome

Triad of symptoms:

A

Hepatic vein thrombosis w centrilobular congestion and necrosis –> congestive liver disease (hepatomegaly, ascites, varices, abdominal pain, liver failure)

Absence of JVD

Associated with hypercoagulable states, esp polycythemia vera

May cause nutmeg liver (mottled appearance)

18
Q

Alpha1-antitrypsin deficiency

A

Autosomal recessive defect of A1AT (a protein that inactivates proteases and protects tissues from their enzymatic destruction)

In lungs, dec. A1AT –> uninhibited elastase in alveoli –> dec. elastic tissue –> panacinar emphysema

In liver, accumulation of A1AT (misfolded gene product) in hepatocellular ER –> cirrhosis + PAS positive globules in liver

** In non-smoker w early onset emphysema, consider A1AT deficiency as cause of cirrhosis

19
Q

Jaundice

A

Abnormal yellow of skin and/or sclera (earliest sign)

Cause:

inc. serum bilirubin, usually > 2.5 mg/dL

Arises w disturbances in bilirubin metabolism

20
Q

A 56-year-old man with a history of alcoholism and liver cirrhosis presents with new onset confusion and irritatibility. He was recently admitted for sepsis caused by pneumonia. On physical exam he has a flapping tremor, ascites, jaundice and is not oriented to time or place.

A

Hepatic encephalopathy

21
Q

Wilson Disease

A
  • Recessive mutations in hepatocyte copper-transporting ATPase (ATP7B gene; xsome 13)
  • Result: inadequate copper transport into bile and blood (lack of copper incorporation into ceruloplasmin)
    • Dec. serum ceruloplasmin
    • Inc. urine copper
22
Q

Wilson Disease:

Presentation & Treatment

A
  • Presents BEFORE age 40/esp in childhood w:
    • Liver disease
      • Hepatitis
      • Acute liver failure
      • Cirrhosis
    • Neurologic disease (due to copper deposition in basal ganglia)
      • Dysarthria
      • Dystonia
      • Tremor
      • Parkinsonism
    • Psychiatric disease
    • Kayser-Fleischer rings (deposits in Descemet membrane of cornea)
    • Hemolytic anemia
    • Renal disease (e.g., Fanconi syndrome - inadequate reabsorption in the proximal renal tubules of the kidney)

Treatment: chelation with penicillamine or trientine, oral zinc

23
Q

Hemochromatosis

A
  • 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)
24
Q

Hemochromatosis:

Presentation & Treatment

A
  • Presents AFTER age 40 when total body iron > 20 g
    • Iron loss through menstruation slows progression in women
  • Classic triad: cirrhosis, DM, skim pigmentation (“bronze diabetes)
  • Also causes:
    • Dilated cardiomyopathy (reversible)
    • Hypogonadism (gonadal dysfunction due to testicular atrophy)
    • Arthropathy (calcium pyrophosphate deposition) - esp. MCP joints
  • HCC = common cause of death

Treatment: repeated phlebotomy, chelation with deferasirox, deferoxamine, oral deferiprone