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62 Cards in this Set

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What are the cystolic hepatocellular enzymes and what are they specific for?
AST: less specific for liver disease (may be elevated with other conditions (MI))

ALT: produced within cells of liver and elevated with liver damage (most sensitive marker)

LDH
What are some substances that are normally excreted in bile?
And what does an elevation of any of these mean?
serum bilirubin
urine bilirubin
serum bile acids


Liver disease
What are some plasma membrance enzymes?
And what does an elevation of any of these mean?
serum Alk phosphatase
serum GGT
Serum 5'nucleotidase

elevation means liver disease
What proteins made in the liver are excreted into the blood?
serum albumin (decrease=liver disease)
prothrombin time (factors V,VII,X,prothrombin, fibrinogen)
elevation = liver disease
What does hepatocytes metabolize?
serum ammonia (increase=liver disease)

aminopyrine breath test (decrease=liver disease)

galactose elimination (decrease=liver disease)
Inflammation, a form of hepatic injury, has what type of pattern of hepatic injury?
Acute or chronic inflammatory cells destroy antigen-expressing hepatocytes by cytotoxic lymphocytes

Granulomas
abscesses
What would cause granulomas?
foreign bodies, organisms, drugs
What does degeneration of the liver look like?
swelling and edema of hepatocytes

Accumulation of specific material:
-retained bile pigments
-iron
-copper
-viral particles
What causes necrosis in the liver?
virtually any significant insult to the liver
What are councilman bodies from?
apoptosis of liver cells from toxic or immunologic causes
What are different patterns of necrosis?
focal: scattered through parenchyma
Zonal: ex:centrilobular necrosis
submassive
massive
When can liver regeneration occur?
It can occur with all liver diseases except for most fulminant diseases
What could hepatocyte proliferation result in?
thickend hepatocyte cords or swirls of immature tubular structures
What is fibrosis a result of? And what results if fibrosis continues?
response of inflammation or direct toxic insult

continuing fibrosis subdivides liver into nodules of regenerating hepatocytes surrounded by scar tissue
When could you get unconjugated hyperbilirubinemia?
-excess production of bilirubin
-reduced hepatic uptake
-impaired bilirubin conjugation
What results in bilirubin overproduction?
-excessive hemolysis of RBCs
-resorption of major hemorrhages
-ineffective erythropoisesis in bone marrow
What causes reduced hepatic uptake of bilirubin?
-drug inteference with membrane carrier systems
-gilbert's syndrome
What causes impaired bilirubin conjugation?
physiologic jaundice in the newborn:
-breast milk jaundice caused by B-glucuronidase in breast milk

genetic deficiences of UGT activity

diffuse hepatocellular disease
Is crigler-najar syndrome type I or type II more severe? Why?
Type I: fatal, complete lack of UGT
When does jaundice occur with conjugated hyperbilirubinemia? And what is it associated with?
when 50% of serum bilirubin is conjugated

Associated with cholestasis, decreased excretion of bilirubin glucuronides and deficiency in canalicular membrane transporters
What are some inherited causes of predominately conjugated hyperbilirubinemia with jaundice?
Dubin-Johnson syndrome
Rotor Syndrome
What are some indications of Dubin-johnson syndrome?
It is autosomal recessive causing defective canalicular secretion of bilirubin conjugates

Liver is brown
most pts are asymptomatic, but jaundiced

Normal life expectancy
pigment inclusions with histology
What are some indications of rotor syndrome?
autosomal recessive
poorly characterized asymptomatic conjugated hyperbilirubinemia
decreased hepatic uptake and storage
decreased biliary storage
What could cause cholestasis?
hepatocellular dysfunction
biliary obstruction
What are some symptoms of cholestasis?
jaundice
pruritis from retention of bile acids OR xanthomas
elevated serum Alk phos
Where does bile pigment acculumate with cholestasis and what does that obstruction cause?
acculumates within hepatic parenchyma and causes dilated bile canaliculi and degenerated hepatocytes:

portal tract distention
bile duct proliferation
edema
periductal neutrophils
necrotic parenchymal foci (may form bile lakes)
What happens if there prolonged obstruction?
portal tract fibrosis and cirrhosis
What is the histology of cholestasis?
enlarged hepatocytes
dilated canalicular spaces
apoptotic cells
kuppfer cells
bile ductular proliferation
edema, bile pigment retention
neutrophilic inflammation and surrounding swollen hepatocytes undergoing degeneration.
What is the treatment options for intrahepatic cholestasis?
liver transplant
What are the treatment options for extrahepatic cholestasis?
surgery to remove obstruction may be possible
When is someone considered to be in hepatic failure? And what is the overall mortality?
when there is loss of more than 80-90% of hepatic function.

Mortality = 70-95%
What are some clincial features of hepatic failure and cirrhosis?
jaudice/cholestasis
hypoaalbuminemia, hypoglycemia and hyperammonemia
increased serum levels of hepatic enzymes:alanine
coagulopathy (elevated PT)
DIC
gynecomastia, testicular atrophy, palmar erythema, spider angiomas of skin
fetor hepaticus
hepatic encephalopathy, hepatorenal syndrome, coma
massive hepatic necrosis
Why does gynecomastia and testicular atrophy occur?
inability of liver to metabolize estrogen
What does hepatic encephalopathy mean?
life-threatening disorder of nervous system where there is edema and astrocytic reaction.

Advanced loss of hepatocellular function leads to exposure of the brain to altered metabolic function:excess ammonia levels)
What are some clincial features of hepatic encephalopathy?
disturbances in consciousness(behavioral abnormalities, confusion, stupor, coma, death)
electroencephalographic changes
limb rigidity and hyperreflexia, seizures, asterixis
What is hepatorenal syndrome?
renal failure in pts with severe liver disease--there is no intrinsic renal distrubances
will kidney function improve if liver function improves in hepatorenal syndrome?
yes
What is the pathophysiology of hepatorenal syndrome?
decreased renal perfusion pressure and GFR
renal vasoconstriction
Is renal ability to concentrate urine retained?
yes.
mimics profound dehydration
What is cirrhosis defined by?
1.fibrosis: generally irreversible
accompanied by reorganization of vascular architecture
formation of abnormal interconnections btw inflow/outflow
2.nodules
disruption of liver parenchymal architecture
What are some causes of cirrhosis?
EtOH liver disease(60-70%)
cryptogenic(10-15%)
viral hepatitis(10%)
biliary diseases(5-10%)
primary hemochromatosis(5%)
wilson disease (rare)
alpha -1-antitrypsin deficiency (rare)
What is the pathogenesis of cirrhosis?
progressive fibrosis
interstitial collagen (types I and III) deposited in all portion of lobule
capillarization of sinusoids
major source of excress collagen
What are the causes of collagen synthesis in cirrhosis?
1.chronic inflammatory conditions with cytokine generation
2.release of cytokines by kupffer, endothelial cells
3.disruption of normal extracellular matrix
4.direct stimulation of stellate(Ito) cells by toxins
What are some clinical features of cirrhosis?
may be NONE
leads to anorexia, weight loss, weakness, osteoporosis, generalized debilitation
When will cirrhosis cause death?
hepatic failure
complications of portal HTN
hepatocellular carcinoma
What is portal hypertension and what causes it?
increased resistnace to portal blood flow and leads to:
ascites
portosystemic venous shunts
congestive splenomegaly
hepatic encephalopathy
What are the characteristics of pre-hepatic portal hypertension?
obstructive thrombosis and narrowing of the portal vein or massive splenomegaly with shunting of blood to spleen
What causes intrahepatic portal hypertension?
cirrhosis, schistosomiasis
veno-occlusive disease
massive fatty change
diffuse, fibrosing granulomatous disease
nodular regenerative hyperplasia
What are characteristics of pre-hepatic portal hypertension?
severe right sided HF
constrictuve peridcarditis
hepatic vein outflow obstruction (budd-chiari)
How does ascites cause portal hypertension?
percolation of hepatic capsular and intestinal serosal lymph into peritoneal cavity
renal retention of sodium and water
How does portosystemic venous shunts cause portal hypertension?
develop at principal sites for portal systemic venous bypass:
-cardioesopheal junction(may rupture, causing hematemesis and death)
-rectum
retroperitoneum
-falciform ligament and umbilicus
How does congestive splenomegaly contribute to portal hypertension?
caused by long-standing congestion and may induce hematologic abnormalities attributable to hypersplenism (anemia, thrombocytopenia)
What is fetor hepaticus?
characteristic body odor:musty or sweet and sour

related to formation of mercaptans by action of intestinal bacteria on sulfur-containing amino acids methionine and shunting of splanchnic blood from portal into systemic-cirrculation
What are characteristics of HBV carriers?
may exhibit normal liver archietecture and hepatocytes
STAIN POSITIVE FOR HBsAg
Is it possible for HCV carriers to not exhibit chronic hepatitis?
no, will always exhibit chronic hepatitis
What can mimic acute viral hepatitis?
drug reactions
What is the clinical morphology of acute viral hepatitis?
-liver is slightly enlarged
-necrosis of scattered hepatocytes, clumps or lobules
-necrotic hepatocytes are eosinophilic and round up(councilman bodies) or swollen (ballooning degeneration)
-lymphocytes present
-macrophages engulf nectrotic hepatocytes
-lobular disarray
-bridging necrosis (more severe disease)
What are ancillary features of acute viral hepatitis?
-hypertrophy and hyperplasia of kupffer cells and sinusoidal lining cells
-portal tract inflammation
-hepatocellular regeneration
-occasionally, cholestasis
What are the clinical morphology of chronic hepatitis?
mild: chronic inflammatory infiltrate limited to portal tracts
progressive: extension of chronic inflammation from portal tracts into parenchyma
bridging necrosis
continued loss of hepatocytes
What clinical features are associated with viral hepatitis?
spider angiomas
palmar erythema
hepatosplenomegaly
hepatic tenderness
What are major causes of death with hepatitis?
cirrhosis
liver failure
hepatic encephalopathy
massive hematemesis (varices)
hepatocellular carcinoma
What is fulminant hepatitis?
hepatic insufficiency progressing from onset to death(or transplantation) within 2-3wks