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GI II Exam 2 > Liver Path 3 > Flashcards

Liver Path 3 Flashcards

1
Q

Autoimmune hepatitis

A

Injury to normal hepatocytes by infiltrating T cells and plasma cells leading to fibrosis/cirrhosis

Lab tests to detect immunologic abnormalities
Characteristic antibodies:
- Anti-nuclear antibodies
- Anti-smooth (actin) muscle antibodies
High level of polyclonal immunoglobulins (IgG)

Chronic disease but usually highly response to immunosuppression by prednisone and azathioprine

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2
Q

prevalence of autoimmune hepatitis

A

Most common in young women

Genetic predisposition (HLA-DR in Caucasians)

~50% of patients with AIH will have * concurrent autoimmune disorders

In Western Europe and North America, where viral hepatitis prevalence rates are relatively low, AIH accounts for roughly 20% of chronic hepatitis in the white populations

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3
Q

Type 1 autoimmune hepatitis:

A

middle-aged women

antinuclear (ANA), anti–smooth muscle (actin) antibodies* (ASMA) and pANCA

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4
Q

Type 2 autoimmune hepatitis:

A

children or teenagers (mostly female)

associated with anti-liver kidney microsomal antibodies (anti-LKM1)*

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5
Q

Histopathology of Autoimmune Hepatitis

A

Autoimmune hepatitis shares patterns of injury with acute or chronic viral hepatitis

Features considered typical of autoimmune hepatitis include:
Extensive interface hepatitis
Plasma cell predominance in the mononuclear inflammatory infiltrates

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6
Q

Robbins key concepts on autoimmune hepatitis

A

There are two primary types of autoimmune hepatitis:

  • Type 1 autoimmune hepatitis is most often seen in middle-aged women and is most characteristically associated with antinuclear and anti–smooth muscle antibodies (ANA and ASMA)
  • Type 2 autoimmune hepatitis is most often seen in children or teenagers and is associated with anti-liver kidney microsomal autoantibodies (anti-LKM1)

Autoimmune hepatitis may either develop with a rapidly progressive acute disease or follow a more indolent path; if untreated, both are likely to lead to liver failure.

Plasma cells are a prominent and characteristic component of the inflammatory infiltrate in biopsy specimens showing autoimmune hepatitis.

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7
Q

drug and toxin causes of liver injury, acute or chronic

A

esp. acetaminophen, ethanol

Exposure to a toxin or therapeutic agent should always be included in the differential diagnosis of any form of liver disease

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8
Q

Acute Hepatitis

A

Symptoms: nonspecific constitutional symptoms; jaundice
Liver chemistry tests: AST & ALT&raquo_space;>Alk phos and TBili
Histologic pattern: lobular disarray with minimal portal changes and no fibrosis

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9
Q

Drug-Induced Liver Injury

A

Bile duct injury

Steatosis and steatohepatitis

Vascular injury/veno-occlusive disease

Neoplasms

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10
Q

Drug and Chemical induced Hepatic Injury

A

Drug-induced liver diseases can mimic all forms of acute and chronic hepatobiliary diseases

Hepatic injury may result from
Direct toxicity
Hepatic conversion to a toxic form

Immune mechanisms..agent acts as hapten

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11
Q

Patterns of Drug- and Toxin-Induced Hepatic Injury

A

The manifestations of drug-induced hepatotoxicity are highly variable*

  • Periportal region: gluconeogenesis, cholesterol and urea synthesis; high oxygen
  • Pericentral region: Glycolysis, bile acid and glutamine synthesis, drug metabolism, p450-dependent bioactivation
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12
Q

prognosis of drug-induced liver injury

A

Except in rare cases of drug-induced chronic hepatitis, the liver injury subsides and disappears after the cessation of treatment with the drug

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13
Q

Drug-Induced Liver Injury examples

A

Hepatocellular injury
- Acetaminophen

Autoimmune hepatocellular injury
- Halothane hepatitis

Cholestatic liver injury
- Estrogen (may have genetic predisposition)

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14
Q

Acetaminophen

A

now the most common cause of acute liver failure necessitating transplantation in the United States

Toxicity is from a metabolic by-product (NAPQI); Zone 3 necrosis (pericentral)

Toxicity is greatly enhanced by concurrent ETOH consumption (upregulation of cytochrome P-450 system)

Antidote is N-acetyl cysteine; must give within 8-12 hours; restores glutathione

The median acute dose causing liver failure is 24 g (48 extra-strength tablets)

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15
Q

Drugs that Induce CYP2E1 Increase Acetaminophen Toxicity

A

**Ethanol

Isoniazid (INH)

Phenobarbital

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16
Q

Reye Syndrome

A

Associated with aspirin (causality not proven)
Rare, potentially fatal syndrome
Predominantly in children
Mitochondrial dysfunction, primarily liver and brain
Extensive accumulation of fat droplets (microvesicular steatosis)
* Acute liver failure without extensive necrosis

17
Q

Key Concepts (Robbins) Drug- or Toxin-Induced Liver Injury

A

Most drugs or toxins affecting the liver may be classified as:

  • Predictable hepatotoxins, acting in a dose-dependent manner and occurring in most individuals.
  • Unpredictable or idiosyncratic hepatotoxins, which happen in rare individuals and which are often independent of dose

Hepatotoxins may cause harm from direct cell toxicity, through hepatic conversion of a xenobiotic to an active toxin, or by immune mechanisms, such as by the drug or a metabolite acting as a hapten to convert a cellular protein into an immunogen.

18
Q

The most common hepatotoxin causing acute liver failure is

A

acetaminophen.

19
Q

The most common hepatotoxin causing chronic liver disease is

A

alcohol.

20
Q

Fatty Liver Diseases

A

Alcoholic Fatty liver:

  • Alcoholic fatty liver
  • Alcoholic steatohepatitis
  • Alcoholic cirrhosis

Non-alcoholic fatty liver disease (NAFLD):

  • Non-alcoholic fatty liver
  • Non-alcoholic steatohepatitis (NASH)
  • Non-alcoholic cirrhosis
21
Q

Overlapping Stages of Alcoholic Liver Injury

A

FATTY LIVER

  • Develops in all drinkers after moderate intake
  • Completely reversible until there is fibrosis
  • Have mild elevation of LFT’s

ALCOHOLIC HEPATITIS

  • Ballooning (swelling) and necrosis of hepatocytes with formation of Mallory bodies
  • Acute inflammation especially around degenerating cells
  • Centrilobular fibrosis
  • 10% mortality acute phase, 70% develop Cirrhosis

CIRRHOSIS
Features of steatosis and alcoholic hepatitis seen in background.

May be partially reversible

22
Q

Mallory Hyaline

A

pink globs

They represent tangles of intermediate keratin filaments complexed with proteins like ubiquitin.

need to think about acute alcoholic hepatitis

23
Q

pericellular fibrosis

A

seen as thin strands that are located in the perisinusoidal space of Disse and surround cords of hepatocytes.

time to stop the drug

24
Q

Pathophysiology Ethanol and NAFLD

A

Both start with large globules of triglyceride in hepatocytes

The steatotic liver is vulnerable to injury.

Hepatocellular injury and fibrosis may develop in the presence of oxidative stress and the proinflammatory activity of cytokines and similar agents.

25
Q

Fatty Liver to Steatohepatitis

A

Further insults must occur to cause continued progressive damage to hepatocytes and promote inflammation/fibrosis

These likely involve:
Inflammatory effects of gut-derived endotoxin
Oxidative stress/lipid peroxidation
Genetic polymorphisms

26
Q

Alcoholic Liver Disease

A

11% of men and 6% of women are alcoholic, but only 10% of those individuals will get cirrhosis

Threshold daily alcohol intake of 40 g is necessary to produce pathologic changes of alcoholic hepatitis.

4 Beers –> Hepatic Injury

27
Q

Key Concepts (Robbins) Alcoholic Liver Disease

A

Alcoholic liver disease is a chronic disorder that can give rise to steatosis, alcoholic hepatitis, progressive steatofibrosis and marked derangement of vascular perfusion leading eventually to cirrhosis.

Consumption of 80 gm/day of alcohol is considered to be the threshold for the development of alcoholic liver disease.

It may take 10 to 15 years of drinking for the development of cirrhosis, which occurs only in a small proportion of chronic alcoholics.

The multiple pathologic effects of alcohol include changes in lipid metabolism, decreased export of lipoproteins, and cell injury caused by reactive oxygen species and cytokines.

28
Q

Non-Alcoholic Fatty Liver DiseaseNALFLD

A

Hepatic steatosis (fatty liver) in individuals who do not consume alcohol or do so in very small quantities

Associated with metabolic syndrome (obesity, insulin resistance or diabetes, hyperlipidemia and hypertension.

29
Q

Non-Alcoholic Fatty Liver DiseasePresentation

A

Asymptomatic patients have elevated Aminotransferase levels (under 250 IU/L) and metabolic risk factors

Liver imaging (ultrasound, computed tomography, or magnetic resonance imaging) obtained for another reason shows fatty infiltration

30
Q

Two patterns of nonalcoholic liver disease

A

Fatty liver (NAFLD): > 5% fatty change but no necroinflammatory change

Non-alcoholic steatohepatitis (NASH): ballooning degeneration, necrosis, lobular inflammation, ± fibrosis

31
Q

RISK FACTORS FOR ALCOHOLIC LIVER DISEASE AND NONALCOHOLIC FATTY LIVER DISEASE

A

alcoholic: amount and duration of alcohol consumption, female, genetic factors, protein-calorie malnutrition

Non-alcoholic liver disease: obesity, type 2 diabetes, dyslipidemia, metabolic syndrome

32
Q

Key Concepts (Robbins) Nonalcoholic Fatty Liver Disease

A

The most common metabolic disorder is nonalcoholic fatty liver disease, which is associated with the metabolic syndrome, obesity, type 2 diabetes mellitus or other impairments of insulin responsiveness, dyslipidemia, and hypertension.

Nonalcoholic fatty liver disease may show all the changes associated with alcoholic liver disease: steatosis, steatohepatitis, and steatofibrosis, even though the features of steatohepatitis (e.g., hepatocyte ballooning, Mallory-Denk bodies, and neutrophilic infiltration) are often less prominent than they are in alcohol-related injury.

Pediatric NAFLD is being increasingly recognized as the obesity epidemic spreads to pediatric age groups, although its histologic features differ somewhat from that seen in adults.

33
Q

Most common Causes of Liver Cirrhosis in USA

A

Chronic alcoholism is the leading cause of cirrhosis in the United States

Chronic hepatitis C is the second leading cause of cirrhosis in the United States

Nonalcoholic steatohepatitis (NASH)

34
Q

chronic hepatitis: staging fibrosis

A

1: portal
2: periportal
3: septal
4: cirrhosis

GI II Exam 2 (16 decks)

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