Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

GI/Nutrition > Hepatic Inflammation and Fibrosis > Flashcards

Hepatic Inflammation and Fibrosis Flashcards

1
Q

Histological Scoring System: Metavir

A
  1. **Inflammation **(reversible)
    • Grade 0: No activity
    • Grade 1: Minimal
    • Grade 2: Mild
    • Grade 3: Moderate
    • Grade 4: Severe
  2. Fibrosis (irreversible)
    • Grade 0: No fibrosis
    • Grade 1: Portal fibrosis
    • Grade 2: Periportal fibrosis
    • Grade 3: Septal fibrosis
    • Grade 4: Cirrhosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Hepatic Necrosis

  • Definition:
  • Can lead to ….
    • Most common causes ….
A
  • Acute cell death
    • Fibrosis in most cases takes years
  • Can lead to acute liver failure (or fulminant liver failure)
    • Most common causes are medications (acetaminophen) and viral hepatitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is fulminant liver failure?

A

acute liver failure that is complicated by coagulopathy and encephalopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Alcohol Content of Various Beverages:

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Alcohol Drinking Pattern Definitions:

  • Binge Drinking
  • Heavy Drinking
  • Excessive Drinking
A
  • Binge Drinking:
    • ​For women, 4 or more drinks during a single occasion
    • For men, 5 or more drinks during a single occasion
  • Heavy Drinking:
    • For women, more than 1 drink per day on average
    • For men, more than 2 drinks per day on average
  • Excessive Drinking:
    • ​includes heavy drinking, binge drinking or both
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
  1. Whta catalyzes this reaction: Ethanol ⇒ Acetaldehyde
  2. What catalyzes this reaction: Acetaldehyde ⇒ Acetic acid
  3. What is the other function of CYP2E1?
A
  1. Ethanol ⇒ Acetaldehyde
    • Alcohol Dehydrogenase (75-80%)
    • Microsomal Ethanol Oxidizing System** **(20-25%), CYP2E1
  2. Acetaldehyde ⇒ Acetic acid
    • Aldehyde Dehydrogenase
  3. Other function of CYP2E1:
    • metabolism of acetaminophen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Effects Of:

  • Increased NADH
  • Increased acetaldehyde
A
  • Increased NADH
    • inhibition of TCA cycle; reduced gluconeogenesis
    • reduced fatty acid oxidation
  • Increased acetaldehyde
    • activates stellate cells to form collagen
    • Microfilaments that maintain intracellular skeleton are sheared (ballooning)
    • Kupffer cells produce tumor necrosis factor alpha (TNF α)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

ALD: Spectrum of Disease

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Risk Factors for ALD

A
  • Quantity of Alcohol
    • >30 g/day in men
    • > 20 g/day in women
  • Outside of meals
  • Binge drinking
  • Hepatitis C
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Lab Abnormalities for ALD:

  • Biochemistry
  • Hematology
A
  • Biochemistry
    • AST/ALT ratio > 2-3
      • If > 3, it is ALD (put your $ on it)
    • ALT usually <300 IU/ml
    • Rarely raised Alk Phos
    • Low Albumin
    • Bilirubin
  • Hematology
    • ​Prolonged INR (advanced disease)
    • Macrocytosis / anemia
    • Thrombocytopenia (advanced disease)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is alcoholic hepatitis treated?

A
  • Abstinence and lifestyle modification
    • nutritional support
    • 8-12 weeks to see improvement
  • Anti-inflammatory drugs
    • glucocorticoids
    • Pentoxifylline (inhibits TNFα)
    • both are only used for alcoholic hepatitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do you decide who to treat for alcoholic hepatitis?

A
  • Discriminant function
    • 4.6 * (PT - PT CONTROL) + T BILI
  • Patients with values > 32 have a 1-month mortality from 30%-50%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the most common cause of elevated transaminases in the U.S.?

A

**Non-Alcoholic Fatty Liver Disease **(NAFLD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is needed in order to diagnose NAFLD?

A

must obtain a history

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is Non-Alcoholic Fatty Liver Disease categorized? (2)

A
  1. Non-alcoholic fatty liver (NAFL)
    • Presence of hepatic steatosis without inflammation or hepatocellular injury (ballooning of hepatocytes)
  2. Non-alcoholic steatohepatitis (NASH)
    • Presence of hepatic steatosis and inflammation with hepatocellular injury (ballooning of hepatocytes) with or without fibrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the stages of NAFLD?

A
  1. Fatty Liver (Hepatosteatosis) ⇒ (10% progress)
  2. Steatohepatitis (NASH) ⇒
  3. Steatohepatitis with Fibrosis (35% OF NASH) ⇒
  4. Cirrhosis (15% OF NASH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is are the associated metabolic syndromes with NAFLD?

A
  1. Obesity (30-100%)
  2. Diabetes (15-50%)
  3. Hypertriglyceridemia (15-80%)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

NAFLD correlations:

  • Prevalence
  • Severity of disease
  • Gender
  • Race/Ethnicity
A
  • Prevalence increases with age
  • Severity of disease (including advanced fibrosis/cirrhosis) increases with age
  • Males > Females
  • Hispanics > Caucasians > African Americans

​Note: Odds for NAFLD increase with higher BMI (obesity)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

_____ is the most common liver disease in children in the US

A

**NAFLD **the most common liver disease in children in the US

  • NASH is present in 18% of these children
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What type of hyperlipedemia has the most impact on increased risk for NAFLD diagnosis?

A
  • Hypertriglyceridemia rather than hypercholesteremia increases risk
  • 3-fold greater risk with triglycerides > 200
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are causes of steatosis and steatohepatitis?

A
  1. Alcohol
  2. Medications
  3. Nutritional
  4. Insulin resistance (IR)
  5. Abetalipoproteniemia
  6. Weight changes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What medications cause steatosis and steatohepatitis?

A
  1. Amiodarone
  2. Steroids
  3. HAART
  4. Tamoxifen
  5. Diltiazem
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are nutritional causes of steatosis and steatohepatitis?

A
  1. TPN
  2. Severe starvation
  3. Refeeding syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Development and Progression of NAFLD

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What do you look for on ultrasound, when looking for a fatty liver?

A
  • fat is bright
  • normal tissue is dark
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the therapeutic strategies for NAFLD?

A
  1. Lifestyle Modifications:
    • decrease oral intake
    • active lifestyle
  2. Prevent/Treat Insulin Resistance
  3. Reduce Oxidative Stress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What was the AASLD statement on weight loss for NAFLD patients?

A
  • Loss of at least 3-5% of body weight necessary to improve steatosis
    • up to 10% may be needed to improve inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What were the results for Pioglitazone vs. Vitamin E or Placebo for NASH?

A
  • RESULTS (primary endpoint)
    • vitamin E vs placebo; 43% vs 19% (p=0.001)
    • pioglitazone vs placebo; 34% vs 19% (p=0.04)
  • Both reduced transaminases
  • Both reduced inflammation
  • Neither reduced fibrosis
  • Patients receiving pioglitazone gained more weight (4.7 kg)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What was the AASLD statement on insulin sensitizing agents?

A
  • Pioglitazone can be used to treat patients with biopsy-proven NASH
    • majority of patients that participated in clinical trials were non-diabetic and long-term safety and efficacy is not established
30
Q

What was the AASLD statement on Vitamin E?

A
  • Vitamin E at a dose of 800 IU/day improves liver histology in non-diabetic patients with biopsy-proven NASH and should be considered first-line therapy
    • Until further data supporting its effectiveness becomes available, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis or cryptogenic cirrhosis
31
Q

How is Hereditary Hemochromatosis acquired?

A

Hereditary Hemochromatosis (HFE gene)

Autosomal Co-dominance

  • C282Y/C282Y (homozygote)
    • accounts for 82-90% of cases
  • **C282Y/H63D **(heterozygote)
32
Q

What is the normal physiology and pathophysiology for the HFE gene?

A
  • HFE regulates the absorption of iron from the small intestine
    • iron is absorbed and mobilized in plasma compartment by transferrin
  • HFE down-regulates transferrin when iron supplies are adequate
  • A defective HFE gene fails to down-regulate transferrin and iron continues to be absorbed from small intestine
    • Iron deposits leads to development of free radicals
33
Q
  • What can Parenteral Iron Overload lead to?
  • What causes Parenteral Iron Overload?
A

leads to liver problems

  • Red cell transfusions
  • Iron-dextran injections
  • Long-term dialysis
34
Q

What causes Secondary Iron Overload?

A

iron found in kuppfer cells

  1. Anemia caused by ineffective erythropoiesis
    • Thalassemia major
    • Sideroblastic anemia
    • Congential dyserythropoietic anemia
    • Congential atransferrinemia
    • Acerulopasminemia
  2. Liver disease
    • Alcoholic liver disease
    • HBV, HCV
    • Nonalcoholic steatohepatitis
  3. Miscellaneous: excessive iron ingestion
35
Q
  • Which population is hemochromatosis most common?
    • How often?
A
  • Most common genetic disease in populations of European ancestry:
    • C282Y, H63D
    • Heterozygous state: 10% in Caucasians (C282Y/WT)
    • Homozygous state in 0.5%- 1% (C282Y/C282Y)
    • C282Y/H63D (compound heterozygote, 3%-5%)
36
Q

What is the clinical presentation of hemochromatosis?

A
  • Liver function abnormalities - 75%
  • Weakness and lethargy - 74%
  • Skin hyperpigmentation - 70% (bronze skin)
  • Diabetes mellitus - 48%
  • Arthralgia - 44%
  • Impotence in males - 45%
  • Electrocardiographic abnormalities - 31%

Note: All present at later age in women due to menstrual blood loss

37
Q

What is the formula for a potential diagnosis of hemochromatosis?

A
38
Q

What is the treatment for hemochromatosis?

A

Phlebotomy

  • Goal serum ferritin < 50
  • Initially weekly phlebotomy
  • Once quarterly thereafter
39
Q

Describe human Cu metabolism:

A
40
Q

What will cause you to consider Wilson’s Disease?

A
  • No one single finding is adequate for diagnosis
  • Consider diagnosis in any patient age 3-40:
    • Unexplained liver disease
    • Acute liver failure
    • Cirrhosis
    • Neurological symptoms
    • Psychiatric symptoms
41
Q

What is required for a diagnosis of Wilson’s Disease?

A

Need 2 of 3:

  • Decreased CP
  • Elevated urine Cu
  • Kayser-Fleishcer rings
42
Q

What are the neurological features of Wilson’s Disease?

(P.S. long card)

A
  • Movement disorders
  • Drooling, dysarthria
  • Rigid dystonia
  • Dysautonomia
  • Migraine headaches
  • Insomnia
  • Seizures
  • Depression
  • Neurotic behavior
  • Personality changes
  • Psychosis
43
Q

How is ceruloplasmin (CP) affected in Wilson’s Disease?

A
  • 95% of homozygotes have level < 20mg/dL
  • High CP levels occur in inflammation and may lead to false negatives
44
Q

How is urinary Cu excretion affected in Wilson’s Disease?

A
  • Urine copper is derived from non-ceruloplasmin copper
  • Rate of excretion in symptomatic patients may exceed 100 microgram/24hrs
45
Q

What can be seen here?

A

Kayser-Fleischer rings

  • Present in Wilson’s disease (Cu deposition)
46
Q

How is the concentration of Cu affected in Wilson’s Disease?

A
  • Normal hepatic copper content 50 μg/g dry weight
    • Homozygous WD > 250 μg/g dry weight
    • Heterozygous WD 20-250 μg/g dry weight
  • Obtain liver biopsy
47
Q

What is used to treat Wilson’s Disease?

A
  • General chelator - induces cupruria
    • **D-Penicillamine **(significant side effects)
    • Trientine
  • Metallothionein inducer, blocks intestinal absorption of Cu
    • Zinc
48
Q
  • What is the function of alpha1 antitrypsin?
  • What larger family of enzymes does it belong to?
  • Where is it predominately produced?
A
  • A1AT is an inhibitor of the proteolytic enzyme elastase
  • It is part of a larger family of structurally unique protease inhibitors, referred to as serpins
  • Predominantly made in the liver
49
Q

What is the prevalence of alpha1 antitrypsin deficiency?

A
  • Most common cause of genetic liver disease in children
  • Most common genetic disease leading to liver transplantation in children
  • Most common cause of genetic emphysema in adults
  • In adults can cause hepatitis, cirrhosis, liver cancer
50
Q

What are the two genes that are involved in A1AT deficiency?

A

M and Z genes

51
Q

Contrast A1AT deficiency in the lungs and liver:

A
  • Lung
    • Loss-of-function mechanism
    • The lack of A1AT allows uninhibited PMN medicated proteolytic damage to connective lung tissue
  • Liver
    • Gain-of-function mechanism
    • Retention of inefficiently secreted A1AT Z molecule in endoplasmic reticulum triggers a series of hepatotoxic events
52
Q

Consequences of the different genetic mutations of A1AT:

  • PiMM
  • PiMS
  • PiMZ
  • PiSS
  • PiSZ
  • Pi
  • PiZZ
A
  • PiMM, 100% activity, no lung or liver disease
  • PiMS, 80% activity, no lung or liver disease
  • PiMZ, 60% activity, no lung or liver disease
  • PiSS, 50-60% activity, no lung or liver disease
  • PiSZ, 30-40% activity, causes lung disease only
  • Pi null-null, 0% activity, causes lung disease only
  • PiZZ, 10-15% activity, can cause both lung and liver disease
    • affects 1/1600-1800 live births
53
Q

How is A1AT deficiency diagnosed?

A
  • Serum A1AT levels
  • A1AT phenotypes
  • Liver biopsy
54
Q

What type of stain is needed to visualize A1AT deficiency?

A

Periodic Acid-Schiff Base stain

55
Q

Autoimmune Hepatitis

  • Definition:
  • What is found in the serum?
  • Type of onset; Gender preference?
  • Incidence:
  • Associations:
A
  • Definition: Hepatocyte inflammation
  • Autoantibodies in serum
  • Insidious or acute onset; F/M 4:1
  • 20-30 cases per million population
  • 50% have other autoimmune disorders
56
Q

Autoimmune Hepatitis

  • Labs:
  • Characterized by ….
A
  • Labs:
    • ALT, AST elevation, occ. > 1000
    • Elevated gamma-globulin or elevated IgG
    • Autoantibodies
  • Characterized by interface hepatitis, portal plasma cell infiltration
57
Q

How is AIH subclassified based on serological markers? (2)

A
  1. Type 1 (Classic, 80-90%, adults)
    • Organelle: nucleus
      • ANA (anti-nuclear antibody)
      • ASMA (anti-smooth muscle antibody)
  2. Type 2 (anti-LKM 1 hepatitis, children)
    • Organelle: microsome
      • Anti-liver-kidney microsomal antibody
58
Q

What conditions are associated with AIH?

A
  • Thyroid disease
  • Rheumatoid arthritis
  • Diabetes
  • Sjogren’s syndrome
  • Polymyositis
  • IgA deficiency
  • Idiopathic thrombocytopenia
  • Urticaria
  • Vitiligo
  • Addison’s disease
  • Inflammatory Bowel Disease
59
Q

What is used to treat AIH?

A
  • Single Therapy
    • Prednisone
  • Combination
    • Prednisone + Azathioprine
60
Q

What are the only two times steroids are used for liver therapy?

A
  1. Alcoholic hepatitis
  2. Autoimmune hepatitis
61
Q

What are the endpoints and prognosis of AIH therpay?

A
  • Treatment endpoints: normal ALT, AST, IgG, gamma-globulin, resolution of inflammation on biopsy
  • Treated patients
    • Response 65% within 18 months
    • Response 80% within 3 years
    • 20-year survival is 80%
  • Untreated patients
    • 50% dead within 3 years
    • 90% dead within 10 years
62
Q

What is Primary Biliary Cirrhosis (PBC)?

A
  • Chronic, progressive, cholestatic liver disease
  • Destruction of intrahepatic bile ducts
  • Probable autoimmune pathogenesis
63
Q

PBC:

Epidemiology

A
  • 25-400/million
  • 3500 new cases/year
  • 90-95% women
  • Predominantly Caucasian
  • Mean age 52 at presentation, range 30-65
64
Q

What is the autoimmune pathogenesis of PBC?

A
  • High prevalence of serum autoantibodies (antimitochondrial antibodies, AMA)
    • present in 95%
  • Elevated IgM
  • Association with other autoimmune diseases
  • Increased familial incidence of disease
    • 6% family history of PBC
65
Q

What is the target site in PBC?

A
  • Major target antigen of the AMA’s are a multi-enzyme complex (pyruvate dehydrogenase complex, PDC)
  • One antigen, PDC-E2 appears to predominate
  • The PDC-E2 which AMA’s target are located on the membrane of the biliary epithelial cells
66
Q

How do asymptomatic PBC patients present?

A
  • Raised Alkaline Phosphatase
  • AMA+
  • Investigation for other autoimmune disease
67
Q

PBC:

Signs and Symptoms

A
  • Asymptomatic - 25%
  • Fatigue - 65%
  • Pruritus - 55%
    • ​due to bile salt deposition
    • bottom of feet most affected
  • Hepatomegaly - 25%
  • Splenomegaly - 15%
  • Jaundice - 10%
  • Xanthelasma - 10%
68
Q

How do fat soluble vitamins become deficient in PBC?

A
  • Decreased bile salt excretion, steatorrhea
  • Correlates with duration and severity of liver disease
  • Vitamins A, D, E, K
    • vitamin D (8-23%): osteomalacia, fractures, regular bone densitometry
    • vitamin K (7-8%): prolonged PT
      • Vit K supplementation will work
69
Q

What disorder is most commonly associated with PBC?

A

Sjogren’s/Sicca Syndrome

70
Q

How are the biochemistry labs affected in a patient with PBC?

A
  • Alkaline Phosphatase: 3-4 x normal in >90%
  • Bilirubin usually rises late
  • Cholesterol elevated in 85%
    • Not associated with heart disease
71
Q

What is the characteristic histological finding in PBC?

A

Florid duct lesion

  • Lymphocytes and mononuclear cells causing inflammatory changes around bile ducts

GI/Nutrition (36 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions