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(J2) GI II Test 2 > Drug, Alcohol, and Metabolic Liver Disease > Flashcards

Drug, Alcohol, and Metabolic Liver Disease Flashcards

1
Q

What is the most common cause of drug-induced liver injury?

A

acetaminophen

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2
Q

How is acetaminophen toxcitiy treated?

(monitoring and treatment)

A
  • Rumack-Matthew nomogram is used to approximate likelihood of hepatic toxicity; based on plamsa acetaminophen and time post injestion
  • 4 hour post-ingestion acetaminophen level is crucial

treatment is with N-acetylcysteine (NAC)

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3
Q

What are examples of dose-dependent hepatotoxins?

A
  • acetaminophen
  • amanita mushroom
  • tetracycline
  • valproic acid
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4
Q

What are idiosyncratic drug reactions?

What types of drugs frequently are implicated in this?

A

reactions to substances that are unpredicatable

  • is not dose-dependnent
  • not present in all people
  • may illicit an immune response or be related to impaired metabloism to substance

antibiotics are the most common cause of idiosyncratic reactions

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5
Q

Where is damage in drug/toxin-induced liver injury commonly seen?

A

zone 3 (perivenular) of the lobule

  • area of highest concentration of P-450
  • many metabolites are directly responsible for liver damage rather than the ingested substance itself
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6
Q

How much alcohol consumption per day is considered “excessive”?

A
  • >80 mg/day in males
  • 30-40 mg/day in females
  • above has significant risk of severe liver injury if occurs for >10 years
  • >160mg/day has expected risk of severe liver damage

a “Standard Drink” contains 10g of alcohol:

  • 12 fl oz beer (5%)
  • 8 fl oz/half pint malt liquor (7%)
  • small glass of wine (5 fl oz)
  • 1.5 fl oz shot (~40%)
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7
Q

What are the types of alcohol-related liver disease?

A
  • alcoholic steatosis (fatty liver)
  • alcoholic steatohepatitis
  • alcoholic steatofibrosis/cirrhosis
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8
Q

What is alcoholic steatosis?

(clinical presentation and labs)

Approximatley how much alcohol consumption is needed?

A

reversible, microvesicular fatty change

-can regress with cessation

can occur with as little as one day of excessive alcohol consumption (>80mg)

Presentation:

  • asymptomatic hepatomegaly
  • mild elevations of alk phos and bilirubin
  • minimal change in AST/ALT
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9
Q

What is alcoholic hepatitis?

Approximatley how much alcohol consumption is needed?

A

reversible, inflammatory damage:

  • swelling/ballooning w/ steatosis
  • necrosis
  • Mallory-Denk bodies (eosinophilic inclusions of keratin filaments)
  • neutrophil infiltrate

acute presentation following episode(s) of heavy alcohol consumption

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10
Q

What is the clinical presentation and lab findings of alcoholic steatohepatitis?

A

Presentation:

  • ranges from asymtomatic to severe liver failure depending on severity
  • anorexia, nausea, vomiting, jaundice, tender hepatomegaly, RUQ pain

Labs:

  • elevated AST/ALT w/ ratio of >2:1 (typcially below 400U/L)
  • elevated bilirubin, alk phos, and GGT
  • leukocytosis w/ left shift
  • possible megaloblastic anemia (folic acid deficiency)
  • thrombocytopenia (direct toxcity or hypersplenism)
  • decreased LFT (increased PT/INR, decreased albumin)
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11
Q

What is alcoholic steatofibrosis?

Approximatley how much alcohol consumption is needed?

A

usually irreversible fibrotic change

  • fibrosis begins around central vein and spreads through space of Disse -> “chicken wire” pattern
  • irreversible with increased severity or progression to cirrhosis

-reversible in early stages with abstinence

-long-term exposure to excessive alcohol consumption (prolonged alcoholic steatosis)

-repeated attacks of alcoholic hepatitis

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12
Q

What is the risk of developing cirrohsis from alcohol consumption alone?

What factors increase the risk of developing cirrhosis?

A

10-15% of chronic alcoholics develop cirrhosis

Risk factors:

  • female (more at risk despite being less prevalent)
  • African American
  • HBV or HCV infection
  • iron overload
  • malnutrition?
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13
Q

How does the body metabolize alcohol?

How does alcohol metabolism cause hepatocyte damage?

A

In the liver:

  • alcohol dehydrogenase, ADH (cytoplasmic): EtOH + NAD+ -> acetaldehyde + NADH
  • acetaldehyde dehydrogenase, ALDH (mitochondiral): acetaldehyde + NAD+ -> acetic acid + NADH

at high blood EtOH levels:

-microsomal P-450 pathway is used -> ROS

damage caused by:

  • consumption of NAD+
  • increased fat catabolism
  • peroxidation of lipid by acetaldehyde
  • production of ROS
  • enhanced drug metabolism (P-450 activation)
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14
Q

What are complications of advanced alcoholic liver disease?

A
  • infection
  • GI hemorrhage (variceal hemorrhage and/or coagulopathy)
  • HCC

-Wernicke encephalopathy

-Korsakoff syndrome

Decompensated cirrhosis:

  • coma (hepatic encephalopathy)
  • ascites (w/ SBP)
  • portal HTN
  • coagulopathy
  • hepatorenal syndrome
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15
Q

What is Wernicke encephalopathy and Korsakoff syndrome?

A

Wernicke encephalopathy (acute and reversible):

  • AMS
  • ataxia
  • saccadic eye movements (nystagmus, diploplia, ophthalmaplegia)
  • treated with thiamine

Korsakoff syndrome (chronic and irreversible):

  • severe memory issues
  • confabulation
  • personality/psych changes
  • no response to thiamine
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16
Q

What lab and clinical finding are poor prognositc inidcators in alcoholic liver disease (indicate severe alcoholic hepatitis)?

A
  • ascites
  • variceal hemorrhage
  • encephalopathy
  • hepatorenal syndrome

severe alcoholic hepatitis:

  • total bilirubin >8-10 mg/dL
  • PTT > 6 sec
  • hypoalbuminemia
  • azotemia
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17
Q

What measures are used to predict prognosis of alcoholic liver disease?

A

Maddrey’s discrminant function (DF):

-calculated with PT and bilirubin

-value >32 is poor prognosis

Glasgow alcoholic hepatitis score:

  • multivariable
  • score >9 is poor prognosis

Model for End-Stage Liver Disease (MELD):

  • value >14 qualifies for liver transplant
  • value >21 indicates significant mortality
18
Q

What are the types of aquired metabolic liver disease?

A
  • non-alcoholic fatty liver disease (NAFLD)
  • non-alcoholic seatohepatitis (NASH)
19
Q

How is alcoholic liver disease treated?

A

Treatment:

-abstinence from alcohol (taper if needed to prevent withdrawal)

Management:

  • thiamine
  • folic acid
  • multivitamin
  • zinc
  • monitor glucose and administer as need (give increased thiamine with glucose)
  • correction of electrolyte deficiencies (potassium, magnesium, and phosphate)
20
Q

What is NAFLD?

A

hepatic steatosis not attributable to alcohol consumption

assocaited with metabolic syndrome:

-one of: DM, impaired glucose tolerance, impaired fasting glucose, insulin resistance

-and-

-two of: HTN (BP > 140/90), dyslipidemia, central obesity, microalbuminemia

21
Q

What is the clinical presentation and lab findings of NAFLD?

A

Presentation:

typically asymptomatic aside from symptoms of metabolic syndrome

Lab findings:

-liver tests normal

-abnormal lab values associated with metaboic syndrome

22
Q

What is NASH?

A

identical histology with alcoholic hepatitis:

  • swelling/ballooning w/ steatosis
  • necrosis
  • Mallory-Denk bodies (eosinophilic inclusions of keratin filaments)
  • neutrophil infiltrate (monocytes may be more prominent)
23
Q

What is the clinical presentation and lab findings of NASH?

A

Presentation:

  • symptoms of metabolic syndrome
  • possible RUQ pain
  • hepatomegaly

Labs:

  • mildly elevated AST/ALT (ratio of less than <1 unlike alcohoic hepatitis)
  • mildly elevated alk phos
  • abnormal lab values associated with metaboic syndrome
24
Q

What are complications of NAFLD/NASH?

A

NAFLD:

-no major complicaitons beyond progression to NASH

NASH:

  • cirrhosis (possible decompensation)
  • HCC
25
Q

How is NAFLD/NASH treated?

A

address metabolic syndrome:

  • control blood glucose levels
  • exercise
  • dietary changes
26
Q

What are the main inherited liver metabolic disorders?

A
  • hemochromatosis
  • Wilson disease
  • α1-antitrypsin deficiency
27
Q

What is the most common inherited liver disorder in infants and children?

A

α1-antitrypsin deficiency

28
Q

What is hemochromatosis?

A

HFE gene defect -> impaired iron sensing -> excessive iron uptake

excess iron is deposited throughout the body:

  • deposits cause symptoms themselves
  • ROS generated by free iron cause damage
29
Q

How does hemochromatosis present?

(when and who?)

A

Often asymmptomatic with insidious presentation later in life (50’s)

  • does not manifest until total body iron ~20g
  • iron acumulates at rate of 0.5-1 g/year
  • more common overall in men; onset later in women (iron accumulation offset by menstruation

“Bronze diabetes”:

-cirrhosis with hepatomegaly

  • bronze skin pigmentation
  • diabetes (pancreatic islet destruction)

additional symptoms:

  • cardiac dysfunction
  • atypical arthritis
  • hypogonadism
30
Q

What are lab/histology findings associated with hemochromatosis?

A

Lab:

  • elevated serum iron
  • elevated ferritin (>200 μg/L
  • elevated transferrin saturation (>45%)
  • elevated AST/ALT

Histologic:

-hemosiderin deposition hepatocytes and macrophages

  • golden-yellow granules
  • stains with prussian blue
31
Q

How is hemochromatosis treated?

A
  • phlebotomy
  • deferoxamine (chelation)
32
Q

What is Wilson disease?

A

ATP7B gene mutation; copper-transporting ATPase

  • desposition of free copper
  • decreased incorperation of copper into ceruloplasmin
33
Q

How does Wilson disease present?

(who and when?)

A

presents under age of 40

Presentation (deposition in liver, brain, and eye):

  • liver disease
  • neuro disease (tremor/ataxia)
  • psychiatric disease
  • deopsition in cornea -> brown/grey-green Kayser-Fleischer ring
  • hemolytic anemia (direct toxicity)
34
Q

What are lab/histology findings associated with Wilson disease?

A

Lab findings:

  • decreased ceruloplasmin
  • elevated liver enzymes (AST/ALT, ALP, bilirubin)
  • increased urinary copper
  • hemolytic anemia

Histology:

-increased hepatic copper

35
Q

What should always raise suspicion of Wilson disease?

A

noninfectious liver disease with extrapyramidal symptoms under the age of 35

36
Q

How is Wilson disease treated?

A
  • oral penicillamine (chelation)
  • liver transplantation (w/ liver failure)
37
Q

What is α1-antitrypsin deficiency?

A

various mutations in the α1-antitrypsin gene resulting in misfolding of the protein

α1-antitrypsin is a protease inhibitor produced in the liver and protects tissues from neutrophil elastase

deficiency -> tissue damage from elastase -> pulmonary emphysema

misfolding -> acummulation in hepatocytes -> liver damage

38
Q

What is the most clinically significant mutation in α1-antitrypsin deficiency?

What group is this most common in?

A

PiZ mutation (homozygous -> PiZZ)

most common in Northern European populations

39
Q

How does α1-antitrypsin deficiency present?

A

Infants:

-neonatal hepatitis w/ jaundice

Adolescents:

  • pulmonary emphysema (**should always consider when seen in children, especially w/o smoking history)
  • hepatitis
  • cirrhosis

Adults:

  • cirrhosis
  • HCC
40
Q

What lab/histology findings are associated with α1-antitrypsin deficiency?

A

Lab findings:

-low α1-antitrypsin

Histology:

-characteristic magenta granules in liver with PAS stain

41
Q

How is α1-antitrypsin deficiency treated?

A
  • avoidance of smoking
  • bronchodilators
  • antitrypsin replacement
  • liver transplantation
42
Q

What should alway raise suspicion of α1-antitrypsin deficiency?

A

emphysema under the age of 50, especially in non-smokers

(J2) GI II Test 2 (12 decks)

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