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Gastrointestinal 1 > Alcoholic and Metabolic Liver Disease > Flashcards

Alcoholic and Metabolic Liver Disease Flashcards

1
Q

What is cirrhosis?

A
  • end-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes.
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2
Q

What mediates cirrhosis?

A
  • TGF-B from perisinusoidal STELLATE cells (cells of ITO), which lie beneath the endothelial cells that line the sinusoids, and other cytokines from Kupffer cells (macrophages of liver). The STELLATE cells become activated and transform to myofibroblasts, contributing to fibrosis. Collagen I and III are deposited in lobule causing loss of fenestrations in sinusoidal endothelial cells. This results in impaired secretion of proteins such as albumin, clotting factors, and lipoproteins. Thus, this leads to edema (ascites) in the abdomen, bleeding, compromised delivery of blood to hepatocytes, and biliary channel injury (jaundice).
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3
Q

What are the 3 clinical features of cirrhosis?

A
  1. PORTAL HYPERTENSION
  2. DECREASED DETOXIFICATION
  3. DECREASED PROTEIN SYNTHESIS
    * also anorexia, weight loss, and impairment of pulmonary oxygenation.
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4
Q

To what will portal hypertension lead from cirrhosis?

A
  • ascites (fluid in the peritoneal cavity)
  • congestive splenomegaly/hypersplenism (increased consumption of RBCs by the spleen).
  • portosystemic shunts (esophageal varices, hemorrhoids, and caput medusae).
  • hepatorenal syndrome (rapidly developing renal failure secondary to cirrhosis).
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5
Q

In what will decreased detoxification from cirrhosis result?

A
  • mental status changes, asterixis (flapping tremor), and eventual coma (due to increased serum ammonia); metabolic, hence reversible.
  • gynecomastia, spider angiomata, and palmar erythema due to hyperestrinism (liver normally removes estrogen from the blood).
  • jaundice
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6
Q

What will decreased protein synthesis lead to from cirrhosis?

A
  • hypoalbuminemia with edema (liver normally produces albumin, and without it you have less onconic pressure).
  • coagulopathy due to decreased synthesis of clotting factors (normally activates vitamin K via epoxide reductase); degree of deficiency is followed by PT (think PT because we use this to follow warfarin and warfarin knocks out epoxide reductase).
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7
Q

What are the 3 classic patterns of presentation for alcohol-related liver disease?

A

All cause damage to hepatic parenchyma due to consumption of alcohol:

  1. Fatty liver (hepatic steatosis)= shunting of substances from catabolism and toward lipid biosynthesis and thus accumulation of fat in hepatocytes. This results in a heavy, greasy liver; resolves with abstinence. Begins as microvesicular but with repeated bouts of alcohol progresses to macrovesicular (not micro- macronodular).
  2. Alcoholic hepatitis= chemical injury to hepatocytes; generally seen with binge drinking.
  3. Cirrhosis= complication of long-term, chronic alcohol-induced liver damage; occurs in 10-20% of alcoholics.
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8
Q

What is the most common cause of liver disease in the West?

A

alcohol-related liver disease

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9
Q

What mediates damage in alcoholic hepatitis?

A
  • ACETALDEHYDE (metabolite of alcohol) induces lipid peroxidation, injuring the hepatocytes.
  • impairment of methionine by alcohol decreases glutathione levels, leading to oxidative injury.
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10
Q

** What characterizes alcoholic hepatitis? (BOARD QUESTION)

A
  • swelling of hepatocytes with formation of MALLORY BODIES (damaged cytokeratin filaments), necrosis, and acute inflammation.
  • presents with painful hepatomegaly and elevated liver enzymes (AST>ALT because AST is located in the mitochondria and alcohol poisons the mitochondria).
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11
Q

What is nonalcoholic fatty liver disease?

A
  • fatty change, hepatitis, and/or cirrhosis that develop WITHOUT EXPOSURE to alcohol (or other known insult).
  • associated with obesity.
  • Diagnosis of exclusion; ALT>AST.
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12
Q

What is hemochromatosis?

A
  • excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (hemochromatosis).
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13
Q

What mediates the tissue damage in hemochromatosis?

A

generation of free radicals (remember bc iron has the ability to generate free radicals in the fenton reaction) due to autosomal recessive defect in iron absorption (PRIMARY) or chronic transfusions (SECONDARY).

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14
Q

What causes PRIMARY hemochromatosis?

A
  • mutations in the HFE gene, usually C282Y (cysteine is replaced by tyrosine at amino acid 28) on chromosome 6 (remember hem-o-chrom-a-tos-is= 6 syllables).
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15
Q

What is the classic triad of hemochromatosis presentation?

A
  1. cirrhosis
  2. secondary DM
  3. bronze skin occurring in late adulthood.
    * additional findings include cardiac arrhythmias and gonadal dysfunction (due to testicular atrophy), depending on where the iron deposits.
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16
Q

What are the lab findings for hemochromatosis?

A

an iron overloaded state:

  • INCREASED ferritin
  • DECREASED TIBC (total iron binding capacity; always opposite ferritin).
  • INCREASED serum iron
  • INCREASED % saturation
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17
Q

What should you do if you suspect hemochromatosis?

A
  • perform a liver biopsy, which will reveal accumulations of brown pigment in hepatocytes. This could be either:
  • lipofuscin= by-product from the turnover (wear and tear) of peroxidized lipids; it is commonly present in hepatocytes.
  • iron from hemochromatosis= PRUSSIAN BLUE stain distinguishes iron (blue) from lipofuscin.
  • think of lipfuscin like gray hairs of hepatocytes. It just means the cell is old.
18
Q

How do you treat hemochromatosis?

A

phlebotomy to decrease RBCs which contain an iron load.

19
Q

For what does hemochromatosis increase your risk?

A

hepatocellular carcinoma bc iron generates lots of free radicals, which can damage the DNA, leading to mutations in the hepatocytes.

20
Q

What is Wilson disease?

A
  • autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocyte copper transport that results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin (molecule that carries copper in the blood).
  • Bc copper cannot get into the blood, it builds up in the hepatocytes, leaks into serum, and deposits in tissues. This leads to copper-mediated production of hydroxyl free radicals= tissue damage.
21
Q

How does Wilson disease present?

A
  • in childhood with cirrhosis, neurologic manifestations (behavioral changes, dementia, chorea, and parkinsonian symptoms due to deposition of copper in basal ganglia), and KAYSER-FLEISHER RINGS in the cornea.
22
Q

What do labs show for Wilson disease?

A
  • INCREASED urinary copper (some will leak into urine)
  • DECREASED serum ceruloplasmin
  • INCREASED copper on liver biopsy.
23
Q

For what does Wilson disease increase your risk?

A

hepatocellular carcinoma

24
Q

What is the treatment for Wilson disease?

A
  • D-penicillamine (chelates copper)
25
Q

What is PRIMARY biliary cirrhosis?

A
  • autoimmune granulomatous destruction of INTRAhepatic bile ducts.
  • classically seen in women
26
Q

** What causes PRIMARY biliary cirrhosis? (TEST QUESTION)

A
  • etiology is unknown but ANTIMITOCHONDRIAL ANTIBODY is present.
27
Q

How does PRIMARY biliary cirrhosis present clinically?

A
  • with features of obstructive jaundice, and cirrhosis is a late complication.
28
Q

What is primary sclerosing cholangitis?

A
  • inflammation and fibrosis of INTRAhepatic and EXTRAhepatic bile ducts.
  • This results in periductal fibrosis with an ONION-SKIN appearance.
  • uninvolved regions are dilated resulting in a “BEADED” appearance on contrast imaging.
29
Q

** With what is primary sclerosing cholangitis associated? (BOARD QUESTION)

A
  • ULCERATIVE COLITIS or inflammatory bowel disease.

* p-ANCA is often positive

30
Q

How does primary sclerosing cholangitis present?

A
  • with obstructive jaundice; cirrhosis is a late complication
31
Q

For what does primary sclerosing cholangitis increase your risk?

A
  • cholangiocarcinoma
32
Q

What is Reye syndrome?

A
  • fulminant liver failure and encephalopathy in CHILDREN with VIRAL illness who take ASPRIN.
  • related to mitochondrial damage of hepatocytes.
33
Q

How does Reye syndrome present clinically?

A
  • hypoglycemia, elevated liver enzymes, and nausea with vomiting; may progress to coma and death.
34
Q

What is MICROnodular (Laennec) cirrhosis?

A
  • nodules less than 3 mm and may progress to MACROnodular.

- caused by alcohol in most countries.

35
Q

What is MACROnodular cirrhosis?

A
  • classically associated with viral chronic hepatitis.

- may result from confluent submassive necrosis

36
Q

What are the causes of cirrhosis?

A
  • ETOH
  • Nonalcoholic fatty liver disease
  • chronic hepatitis
  • biliary disease (obstruction, primary biliary cirrhosis, sclerosing cholangiits).
  • metabolic disease
37
Q

What is a potentially lethal blood alcohol level?

A

0.3-0.5 (for average point).

38
Q

What does alcohol release that causes potent vasoconstriction?

A

endothelins, thus leading to regional hypoxia

39
Q

How does alpha-1 antitrypsin deficiency affect the liver?

A
  • causes low levels of alpha-1 antitrypsin, a protease inhibitor to elastase, which normally prevents break down of elastic tissue in the body.
  • This permits tissue destructive enzymes to go unchecked.
  • may present as liver or lung disease or both.
  • increased risk for hepatocellular carcinoma.
  • REMEMBER chromosome 14, and genetic mutation is in PiZ
40
Q

Where does A1AT-Z accumulate in alpha-1 antitrypsin deficiency?

A

in the endoplasmic reticulum of hepatocytes

41
Q

With what may A1AT be associated?

A

Wegener’s granulomatosis, bronchiectasis, and arterial aneurysms.

42
Q

What is SECONDARY biliary cirrhosis?

A
  • EXTRAhepatic bile duct obstruction
  • causes jaundice, pruritis, and dark colored urine.
  • excess conjugated hyperbilirubiniemia

Gastrointestinal 1 (21 decks)

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