Liver Pathology Part II Flashcards
1
Q
Hepatitis Genomes?
A
A, C, D, E - ssRNA
B - dsDNA
2
Q
Hepatitis routes of transmission
A
A, E - fecal-oral
B - parenteral, sexual transmission
C, D, - parenteral
3
Q
Hepatitis and chronic liver disease?
A
A - never
B - 5-10%
C - > 80%
D - same as HBV
E - Only immunocomprimised
4
Q
Diagnosis of hepatitis?
A
A - Serum IgM against HAV
B - Hep B antigens
C - HCV RNA
D - HDV RNA or antibodies against
E - HEV RNA or antibodies against
5
Q
Syndromes of hepatitis infection? (5)
A
- Asymptomatic with recovery
- Acute symptomatic with recovery
- Chronic hepatitis
- Fulminant hepatic failure (rare)
- Long-term untreated HBV or HCV can progress to cirrhosis or carcinoma
6
Q
Where is hepatitis A common?
A
Places with poorer hygiene
7
Q
Clinical features of hepatitis A?
A
- Usually fatigue, nausea, jaundice
- Often asymptomatic
8
Q
Hepatitis A is almost always ______ and never enters a chronic carrier state, but can rarely cause _______
A
Self-limited; fulminant hepatic failure
9
Q
Most prevalent form of hepatitis worldwide?
A
Hepatitis B
10
Q
Most people worldwide living with hepatitis B acquired it where?
A
At childbirth
11
Q
Clinical course of hep B? (5)
A
- Acute hepatitis w/ recovery/clearance
- Non-progressive chronic hep
- Progressive chronic disease = cirrhosis
- Fulminant hepatitis w/ massive liver necrosis
- Asymptomatic carrier state
12
Q
What is the best predictor of hepatitis B chronicity?
A
Age
13
Q
Clinical features of acute HBV? (5)
A
- Nonspecific constitutional Sx: fever, anorexia
- Jaundice
- URQ pain
- No sx
- Hepatic failure (rare)
14
Q
Risk factors for HCV?
A
- IV drug use
- Blood transfusions
15
Q
What are hallmarks of HCV?
A
Persistent infections and chronic hepatitis
16
Q
What occurs in majority of HCV-infected individuals?
A
Progression to chronic disease
17
Q
How can chronic HCV be cured?
A
Antiviral regimes are matched to genotype of HCV - commonly 1a or 1b in NA
18
Q
Most common indication for liver transplantation?
A
HCV
19
Q
What form needs co-infection with hepatitis B for its life cycle?
A
HDV
20
Q
Which form of viral hepatitis is from zoonosis resulting in self-limited hepatitis?
A
HEV
21
Q
Hepatitis E is associated with a very high mortality rate in which population?
A
Pregnant women
22
Q
3 forms of alcoholic liver injury?
A
- Hepatitis
- Hepatic steatosis
- Steatofibrosis including cirrhosis
23
Q
Major pathologic pattern of hepatitis?
A
- Liver cell necrosis
- Inflammation
- Mallory bodies
- Fatty change
24
Q
Major pathologic pattern of cirrhosis?
A
- Fibrosis
- Hyperplastic nodules
25
Major pathologic pattern of steatosis?
- Fatty change
- Perivenular fibrosis
26
Alcohol promotes movement of _________ from the gut into the _______ causing liver inflammation
Bacterial endotoxin; liver inflammation
27
Liver inflammation stimulates the release of ______ from sinusoidal endothelial cells, resulting in ________ and _______ of the activated stellate cells
Endothelins; Vasoconstriction and contraction
28
What are endothelins?
Potent vasoconstrictors released from capillary endothelial cells = decreased hepatic sinusoidal perfusion
29
What is alcohol metabolized into? What can this cause
Acetaldehyde = toxic and can cause lipid peroxidation if high concentrations
30
Alcohol metabolism reduced what? What is the result of this?
NAD+ => necessary for fatty acid oxidation therefore fat accumulates in liver
31
Metabolism of alcohol by CYP2E1 results in what?
Free radical production
32
Cellular findings of alcoholic steatohepatitis? (3)
- Hepatocytes ballooned by accumulation of fat in vacuoles
- Immune cells surrounded by dying hepatocytes
- Ubiquitiniylated keratin = collapse of cytoskeleton
33
Clinical features of alcoholic liver disease?
Non-specific sx: malaise, anorexia, weight loss, upper ab discomfort, hepatomegaly
34
Forms of NAFLD?
- Non-alcoholic steatohepatitis (NASH)
- Simple hepatic steatosis and steatosis complicated by inflammation
34
When does alcoholic hepatitis hend to appear?
Acutely following bouts of heavy drinking
35
Is alcoholic steatosis reversible?
Usually reversible upon cessation of alcohol use
35
Most common cause of liver disease in the USA?
Non-alcoholic fatty liver disease (NAFLD)
36
NASH progression?
- 10-20% of cases = liver cirrhosis
- If cirrhosis, possibly liver cancer
37
Pathologic findings of NASH?
- Hepatocyte ballooning, lobular inflammation. steatosis
- Fibrosis => cirrhosis
38
What is NASH strongly associated with?
Obesity and metabolic syndrome
39
Pathophysiology of NASH is a two hit model involving?
1. Hepatic fat accumulation
2. Increased oxidative stress
40
What do free radicals cause?
Lipid peroxidation of the accumulated intracellular fat
41
Obesity seems to be associated with reduced intestinal barrier function, resulting in what?
Increased inflammation in the liver
42
Clinical features of NASH?
- Usually asymptomatic until hepatic failure
- Fatigue and right-sided abdominal pain
- Increased risk of hepatocellular carcinoma
43
What is a frequent cause of heath in those with NASH?
CVD
44
NASH definitive diagnosis?
Detection of fibrosis via imaging or biopsy
45
Most common cause of fulminant hepatitis?
Drug and toxin-induced liver disease
46
Pathological patterns and clinical presentations of drug and toxin-induced liver disease?
- Insidious onset or rapid
- Hepatocyte necrosis, cholestasis, or insidious onset liver dysfunction
- Histologically similar to viral hep
47
Toxins can: (3)
- Be directly toxic
- Be converted by the lier into an active toxin
- Elicit an immune response by acting as a hapten
48
Most drugs or toxins affecting the liver can be classified as what?
1. Predictable hepatotoxins
2. Unpredictable or idiosyncratic hepatotoxins
49
What are predictable hepatotoxins?
Dose-dependent, occur in most individuals
50
What are unpredictable or idiosyncratic hepatotoxins?
Independent of dose, rare
51
What is the most common hepatotoxin causing acute liver failure?
Acetaminophen
52
What is the most common hepatotoxin causing chronic liver failure?
Alcohol
53
Acetaminophen in low-doses?
95% of the time = Detoxification by phase II enzymes, conjugated and excreted in the urine
54
Acetaminophen in high doses?
5% of the time = increased production of NAPQI, if GSH reserves are insufficient, then this molecule will damage hepatocytes
55
Etiology of autoimmune hepatitis?
- Involves attack by cytotoxic T lymphocytes
- Likely genetic, can be triggered by certain medications (statins) or viral infection
56
Type of autoimmune hepatitis with presence of ANA and anti-smooth muscle antibodies, HLA DR3?
Type I (most common)
57
Population that type I autoimmune hepatitis is most common in?
Middle-ages to older individuals
58
Type of autoimmune hepatitis with presence of anti-CYP450 antibodies?
Type II
59
Population that type II autoimmune hepatitis is most common in?
Children and teenagers
60
Prognosis of autoimmune hepatitis?
- Most patients have mild disease = watch and wait with good prognosis
- Severe untreated has mortality of 40%
61
What is caused by a combination of increased resistance to blood flow
through the portal circulation, and a “hyperdynamic circulation”?
Portal hypertension
62
Pre-hepatic causes of portal hypertension?
Thrombosis and obstruction of portal vein
63
Intra-hepatic causes of portal hypertension?
Cirrhosis from any cause
64
Post-hepatic causes of portal hypertension?
Severe R-sided CHF
65
Typical complications of portal hypertension? (4)
- Ascites
- Formation of portosystemic venous shunts
- Congestive splenomegaly
- Hepatic encephalopathy
66
Features of portal hypertension? (7)
- Hepatic encephlaopathy
- Esophageal varices
- Splenomegaly
- Malnutrition
- Spider angiomas
- Caput medusae
- Ascites
67
Why might hyperdynamic circulation occur to intestines and stomach?
Possibly impaired lier clearance of vasodilatory substances
68
What are esophageal varices?
Collateral veins that allow some drainage to occur, but result in enlarged, fragile, congested subepithelial and
submucosal venous plexus within the distal esophagus
69
Why does cirrhosis result in portal hypertension and the development of varices?
Cirrhosis causes necrosis and fibrotic bridging that interrupts the normal flow from triad to hepatic vein = blood being diverted from liver to systemic veins nearby
70
How bad are esophageal varices?
- May rupture and cause massive hematemesis = medical emergency
- As many as half of patients die from the first bleeding episode
71
Pathology that affects the ducts and ductules within the liver?
Intrahepatic biliary tract disease
72
Secondary biliary cirrhosis?
Secondary to uncorrected bile duct obstruction of the extrahepatic biliary tree
73
Primary biliary cirrhosis (PBC)?
- Autoimmune, non-supparative inflammation that destroys the intrahepatic bile ducts
- Portal inflammation leads to scarring and eventually cirrhosis
74
Primary sclerosing cholangiitis (PSC)?
- Intrahepatic and extrahepatic bile ducts become inflamed and the ducts become obliterated
- The unaffected areas dilate, leading to the appearance of ‘beads on a string’
75
Major initial presentation of primary biliary cirrhosis (PBC)?
- Pruritus
- Fatigue
- Abdominal discomfort
76
What are later presentations of PBD?
- Skin pigmentation
- Xanthelasmas
- Steatorrhea
- Vitamin D malabsorption
77
Pathogenesis of PBC?
Anti-mitochondrial antibodies against pyruvate DH and T cells that recognize this antigen are present
78
Major initial presentation of primary sclerosing cirrhosis (PSC)?
- Fatigue
- Pruritis
- Jaundice
79
Later presentation of PSC?
- Chronic liver disease => cirrhosis usually occur
- 7% develop cholangiocarcinoma
- Increased risk of colon cancer
80
Pathophysiology of PSC?
- Likely autoimmune
- Associated with HLA-B8 and p-ANCA
81
PSC epidemiology?
- Presents in early adulthood-middle age
- M > F
- Greatly increased in those with ulcerative colitis
82
Specific pathologic findings for PBC?
- Destruction of interlobular bile ducts
- Patchy involvement (not all ducts)
- Severe cholestatic findings at end-stages and hepatomegaly
83
Specific pathologic findings for PSC?
- Large duct inflammation similar to UC
- Strictures can develop
- Smaller ducts often have little inflammation and show "onion skin" fibrosis
- Similar severe cholestatic findings at end-stage as PBC
84
Acute inflammation of the gallbladder, precipitated 90% of the time by obstruction of the neck or cystic duct
Acute cholecystitis
85
Most common reason for emergency cholecystectomy?
Acute cholecystitis
86
What causes acute cholecystisis?
Results from chemical irritation and inflammation of the obstructed gallbladder
87
In acute cholecystitis, mucosal phospholipases _____ luminal lecithins to what?
Hydrolyze; toxic lysolecithins
88
In acute cholecystitis, what happens to the normally protective mucous layer, what does this cause?
Layer is disrupted => exposing mucosal epithelium to bile salt detergent action
89
In acute cholecystitis, PGs released and GB distention cause what?
Inflammation = dysmotility
90
Clinical features of acute cholecystitis?
- Begins with progressive RUQ pain
- Mild fever
- Anorexia
- Tachycardia
- Sweating
- Nausea and vomiting
91
What are most patients with acute cholecystitis free of?
Jaundice
92
In acute cholecystitis, what will rupture cause?
Severe peritonitis and bleeding
93
Chronic cholecystitis is associated with that in >90% of cases?
Cholelithiasis
94
Why is the cause of chronic cholecystitis obscure?
Not clear that gallstones play a direct role in initiation of inflammation or pain
95
What does supersaturation of bile do?
Predisposes to chronic inflammation
96
Clinical features of chronic cholecystitis?
Recurrent attacks of either steady or colicky epigastric or RUQ pain
97
Complications of chronic cholecystitis?
- Bacterial superinfection with cholangitis or sepsis
- GB perforation/local abscess formation
- Biliary enteric fistula
Porcelain GB
98
What is porcelain GB?
Dystrophic calcification within the wall of the gall bladder, greatly increases risk of cancer
99
Bacterial infection of the bile ducts?
Cholangitis
100
What can cholangitis be a result of?
Any lesion that creates obstruction to bile flow, most commonly choledocholithiasis and biliary strictures
101
What bacteria can cause cholangitis?
Gram (-) aerobes: E. coli, Klebsiella, Enterococcus, Enterobacter
102
Clinical presentation of cholangitis?
- Acute onset fever, chills, abdominal pain, jaundice
- Acute inflammation of bile duct walls = entry of neutrophils
103
What is the main concern of cholangitis?
Sepsis
