Ch 18 Robbins part I Flashcards
Serum alkaline phosphatase tests look for damage to the?
Bile canaliculus
What are some tests that look for hepatocyte synthetic function?
1) Coagulation factors: PT, PTT, fibrinogen, prothrombin, factors V, VII, IX, and X
2) Serum ammonia
What are reversible changes in hepatocytes?
Steatosis and cholestasis (Accumulation of fat and bilirubin in the liver respectively)
Hepatocyte necrosis is the predominant mode of death in what type of injury?
Ischemic/hypoxic injury
What are signs of hepatocyte apoptosis?
1) Councilman bodies (aka acidophil bodies)
2) Yellow fever
Regarding regeneration in the liver, stem cell replenishment is not a significant part of?
Parenchymal repair
Acute hepatic failure is associated with what potential complications?
Encephalopathy and coagulopathy
What are common causes of acute hepatic failure?
1) Acetaminophen
2) Hepatitis A
3) Hepatitis B
4) Hepatitis C
5) Hepatitis D
6) Drugs
7) Hepatitis E
8) Fatty change of microvesicular type
What distinct morphology of acute hepatic failure is characterized by diffuse poisoning of liver cells without obvious cell death and parenchymal collapse; related to fatty liver of pregnancy or idiosyncratic reactions to toxins?
Diffuse microvesicular steatosis
Clinically, what levels are moderately increased with acute hepatic failure?
Liver transaminases
The decline in serum transaminase is not an indication of recovery but instead an indication of?
Fewer viable hepatocytes
What features of acute hepatic failure would indicate poor prognosis?
1) Decrease in liver enzymes
2) Depleted hepatocytes
3) Worsening jaundice, coagulopathy, and encephalophy
What characteristic sign of hepatic encephalopathy causes nonrhythmic, rapid extension-flexion of the head and extremities?
When is it seen in arms?
1) Asterixis
2) Extension and dosriflexed wrists
Coagulopathy which is a sequelae of acute hepatic failure is characterized by?
What is an early sign?
What can it lead to?
1) Impaired clotting due to lack of production of Vitamin K dependent factors
2) Easy bruising
3) Intracranial bleeding
What sequelae of acute hepatic failure is characterized by the liver failing to remove activated coagulation factors from circulation?
Disseminated intravascular coagulation
Portal HTN which is a sequelae of acute hepatic failure can lead to?
Ascites and hepatic encephalopathy
What sequelae of acute hepatic failure is characterized by decreased GFR, elevated serum BUN and creatinine?
Hepatorenal syndrome
Which forms of hepatitis are associated with chronic liver failure?
Hepatitis B and C
Cirrhosis is defined as diffuse transformation of the entire liver into?
Regenerative parenchymal nodules surrounded by fibrous bands and variable degrees of vascular shunting
What helps monitor the decline of the patients on the path to chronic liver failure?
What is classified as “well compensated” and what is “decompensated”?
1) Child-Pugh classification of cirrhosis
2) Class A and C respectively
Broad bands of dense scar with dilated lymphatic spaces and less parenchyma increases the incidence for?
Portal HTN
Palmar erythema, spider angiomata, hypogonadism, and gynecomastia are clinical symptoms of cirrhosis before it becomes end-stage in males due to?
Hyper-estrongenemia from impaired metabolism
What is the most common cause of portal HTN?
Cirrhosis
Ascites is characterized by excess fluid in?
How is the fluid described?
1) Peritoneal cavity
2) Serous fluid
Splanchnic vasodilation which is a mechanisms leading to ascites is characterized by?
Transudation (protein-poor) into the abdominal cavity
What portosystemic shunt is associated with 40% of patients with advanced cirrhosis and its rupture can cause massive hematemesis?
Esophageal varices
What portosystemic shunt is associated with the rectum?
Hemorrhoids
Hepatopulmonary syndrome is exacerbated in what body position and why?
Upright position due to gravity
Which form of hepatitis is benign and self limited?
What does it not cause?
1) Hepatitis A
2) Chronic hepatitis or a carrier state
What confers long term immunity in hepatitis A?
IgG
Chronic hepatitis B virus is an important precursor for?
Hepatocellular carcinoma
Which serum marker for HBV appears before the symptoms, peaks during the overt disease, and lasts for about 12 weeks?
HBsAg
Which serum marker for HBV may persist for life and confers protection?
Which form provides the immunity?
1) Anti-HBs Ab
2) IgG form
Which serum marker for HBV is an indicator of continued viral replication, infectivity, and probably progression to chronic hepatitis?
Persistent HBeAg
Which serum marker for HBV appears just before the onset of symptoms and shows up with increased aminotransferase levels?
Anti-HBc Ab
What association causes an increased probability of chronicity for HBV?
Younger age
In chronic HBV what does the liver biopsy show?
Finely granular ‘ground glass’ hepatocytes packed with HBsAg
Which form of Hepatitis is clinically milder than HBV but 80-90% of patients develop chronic infection and 20% get cirrhosis?
Hepatitis C virus
What clinical finding is associated with HCV?
Chronic HCV infection results in persistent elevations of?
What is found in ~35% of individuals with chronic hepatitis C infection?
When is HCV-RNA detected in the blood?
1) Repeated bouts of hepatic damage
2) Serum aminotransferases
3) Cryoglobulinemia
4) During active infection
Chronic HCV shows what distinctive morphology?
1) Lymphoid aggregates
2) Fatty change of scattered hepatocytes
The vaccine for HBV also prevents?
HDV infection
HDV has the highest rate of acute hepatic failure in what population?
IV drug users
What does a superinfection mean in terms of hepatitis?
When a chronic carrier of HBV is exposed to a new inoculum of HDV
What occurs during the acute phase of a superinfection?
1) Active HDV replication
2) Suppression of HBV with high transaminase levels
What occurs during the chronic phase of a superinfection?
1) HDV replication decreases
2) HBV replication increases
3) Disease progresses to cirrhosis and sometimes hepatocellular carcinoma
What is the characteristic feature of HEV?
Higher mortality rate among pregnant women
Which form of hepatitis is most likely to progress to a chronic state?
Which never progress to a chronic state?
1) HCV
2) HAV and HEV
What is the morphology for severe acute hepatitis?
Confluent necrosis of hepatocytes around central veins
What circulating antibodies are present in type 1 autoimmune hepatitis?
Which are present in type 2 autoimmune hepatitis?
1) ANA (anti-nuclear) and ASMA (anti-smooth muscle)
2) Anti-LKM1 (anti-liver kidney microsome-1)
What is seen in the early phase of severe parenchymal destruction followed by rapid scarring?
Hepatocyte ‘rosettes’ in areas of activity
What are a prominent and characteristic component of the inflammatory infiltrate in biopsy specimens showing autoimmune hepatitis?
Plasma cells
What drug is the most common cause of acute liver failure necessitating liver transplant in the USA?
It is due to a toxic metabolite produced from the CYP450 breakdown in?
1) Acetaminophen
2) Acinus zone 3 hepatocytes
What are intracellular eosinophilic aggregates of intermediate filaments (keratin 8 & 18, ubiquitin) in ballooning hepatocytes?
When can these be seen?
1) Mallory-Denk bodies
2) Alcoholic hepatitis and NAFLD
What is damaged with Mallory-Denk bodies?
Intermediate filaments
What does the scarring look like with alcoholic steatofibrosis?
What type of cirrhosis is involved in this?
1) Chicken-wire fence pattern
2) Laennec cirrhosis
What effect does alcoholic hepatitis have on the CYP450 system?
1) Induces it
2) Decreases glutathione levels
At what AST:ALT ratio is alcoholic liver disease suspected?
AST:ALT > 2:1
What is the most common cause of chronic liver disease in the USA?
Nonalcoholic fatty liver disease (NAFLD)
Nonalcoholic fatty liver disease has increased incidence with?
1) Obesity
2) Metabolic syndrome
In the pathogenesis of NAFLD, what does insulin resistance lead to?
Mitochondria is further damaged by decreased autophagy and forms?
What correlates with stage of fibrosis in NAFLD?
1) Hepatic steatosis
2) Mallory-Denk bodies
3) Level of hedgehog pathway activity
While NAFLD overlaps with histology of alcoholic hepatitis, what is the difference?
1) Mononuclear cells more prominent
2) Portal fibrosis more prominent
3) Mallory-Denk less common
Hereditary hemochromatosis is caused by a mutation in?
This leads to what being abnormal?
1) HFE gene
2) Intestinal absorption of dietary iron
What is the main regulator of iron absorption?
Hepcidin
What effect does hemochromatosis have on the liver?
On the heart?
On the skin?
1) Small, shrunken liver with micronodular cirrhosis
2) Brown coloration
3) Gray-slate coloration
Hemochromatosis has a 200x increased risk of?
Hepatocellular carcinoma
How is hemochromatosis diagnosised?
Presence of iron in tissues with Prussian blue stain
What is due to an autosomal recessive disorder via mutation of ATP7B?
What does it lead to?
1) Wilson disease
2) Copper excretion into bile is reduced leading to copper accumulation in liver
What distinct morphological changes are seen in Wilson disease?
1) Mallory-Denk bodies
2) Basal ganglia atrophy
What happens to urinary excretion of copper in Wilson’s disease?
What happens to plasma ceruloplasmin?
1) Elevated
2) Low
What is the most sensitive and accurate way to diagnose Wilson’s disease?
Increased hepatic copper content
What is the most commonly diagnosed inherited hepatic disorder in infants and children due to a PiZZ genotype?
α1-antitrypsin deficiency
What can α1-antitrypsin deficiency lead to because activity of destructive proteases is not inhibited?
Pulmonary emphysema
α1-antitrypsin deficiency is positive for what following diastase digestion of the liver?
PAS (+)
