Liver Flashcards
Top 4 causes of chronic liver disease
Hep C, Alcoholic liver disease, non alcoholic fatty liver, hepatitis B
Liver tests-Hepatocyte integrity
Aminotransferases(AST, ALT), LDH
Is LDH specific to liver?
No
Tests to measure hepatocyte function
serum albumin, prothrombin time, serum ammonia
Liver tests-Bile canaliculus enzymes. Present during times of bile obstruction
Alkaline phosphatase, 5’-Nucleotidase, Gamma glutamyl transpeptidase
Equation for total bilirubin
Unconjugated+conjugated
normal levels of total bilirubin
0.1-1.2 mg/dL
Level of bilirubin leading to jaundice
> 2 mg/dL
where does conjugation take place
in hepatocytes
Clinical manifestations of hyperbilirubinemia
jaundice and cholestasis
3 mechanisms of jaundice and cholestasis
Isolated disorders of bilirubin metabolism, liver disease, bile duct obstruction
Prehepatic
too much red cell breakdown, leads to increased levels of unconjugated bilirubin. Heme gets into splenic macrophages, enzymes convert heme to biliverdon which is converted to bilirubin in unconguated form.
Hepatic
Bilirubin conjugated, but can’t leave liver. Could also be unconjugated
Posthepatic
Conjugated bilirubin
Where in hepatocyte does conjugation take place
ER. UGT1A1 adds sugar moities to bilirubin.
Function of MRP2,3
Excretion of conjugated bilirubin
Mechanisms of unconjugated bilirubin
overproduction, reduced uptake, defective conjugation
Mechanisms of conjugated hyperbilirubinemia
Defective excretion, Defective secretion
Age group with difficulties with impaired uptake of bilirubin and reduced glucuronyl transferase activity
Newborn
Diseases causing conjugated hyperbilirubinemia
Crigler-Najjar syndrome Types I and II, Gilbert syndrome. Born with all these
Diseases causing conjugated hyperbilirubinemia
Dubin Johnson syndrome, Rotor syndrome
Describe Gilbert syndrome
Autosomal recessive, UGTIAI promoter mutation leads to decreased activity, jaundice during times of stress, normal liver/healthy life. No treatment
Describe Crigler Najjar syndrome Type I
UGTIAI ABSENT. Get super high levels of unconjugated bilirubin. At birth, BB barrier not fully developed, bilirubin can get into brain and cause kernicterus. Very severe. Mental retardation if not death. Treat with phototherapy, transplant
Crigler Najjar Syndrome Type II
Decreased activity of UGT1A1, but more severe than Gilbert. Do respond to phenobarbital unlike CNS Type I.
Describe Dubin Johnson Syndrome
Defect in multidrug resistance protein 2, so bilirubin can’t get into canicular system, can’t be secreted from hepatocyte. Pt gets black liver due to metabolic products of epinephrine? No inflammation/fibrosis
Rotor syndrome
asymptomatic jaundice. Normal liver labs, increased total coproporphyrin, normal isomer I.
Describe progressive familial intrahepatic cholestasis
Defect in biliary epithelial transporters. Presents usually in childhood with progressive cholestasis. Leads to fibrosis/cirrhosis. Leads to failure to thrive, hepatic failure and need for liver transplant
Contents of normal bile
cholic, chenodeoxycholic acid taurine/glycine salts, cholesterol, lecithin, bilirubin, bicarbonate.
PFIC-2
problem with transport of bile salts
PFIC-3
problem with transport of phosphatidylcholine
PFIC-1
problem with ATPase in canicular area, trouble shunting stuff into canicular system
complications of progressive familial intrahepatic cholestasis
cholestasis, fat malabsorption, fat soluble vitamin deficiency, osteopenia, liver failure
Diseases that can occur that effect hepatocellular function with bilirubin. These effect the cells themselves
Viruses, alcoholic liver disease, drugs including chlorpromazine, erythromycin, hepatotoxins, metabolic disorders, pregnancy-toxemia, preclampsyia, immune-PBC and PSC
2 most common causes of posthepatic dysfunction (obstruction of bile duct)
gallstones and carcinoma of ampulla of vater
clinical presentation of pt with cholestasis
Pruritis, jaundice, clay colored stools, dark urine, bleeding diathesis (prothrombin time elevated), xanthomas, osteoporosis.
labs results for cholestasis
increased AP, GGT, 5-Nucleotidase. Hyperbilirubinemia greater than 1.2, hyperlipidemia
what causes bile lake
extrahepatic cholestasis due to obstruction
Cirrhosis
inflammation, fibrosis, bridging bw microscopic structures of liver. Once nodules form have full blown cirrhosis
4 common causes of cirrhosis
Mainly alcholic liver disease, viral hepatitis, obesity. Cryptogenic to a lesser extent
Problems associated with decompensated cirrhosis.
Portal hypertension>12 mmHg, hepatorenal syndrome, liver failure, hepatic encephalopathy
complications of portal hypertension
Gastroesophageal varices, rectal varices, caput medusae, ascites, hypersplenism
Ascities- SAAG level in portal hypertension, non portal HTN
greater than 1.1 g/dL, less than 1.1 g/dL
Hepatic failure
Loss of >80% of liver function
Fulminant is entire wipe out of architecture of liver
Subfulminant-Central veins and around outside of lobules will be destroyed
clinical manifestation of hepatic failure
Encephalopathy, coagulopathy, jaundice, multi organ failure
Hepatorenal failure
renal failure occurs bc cirrhosis or fulminant liver failure. Altered blood flow to kidney causes failure.
Hepatorenal syndrome
Liver failure plus renal failure, normal kidney, oliguria/anuria, increased BUN, creatinine, low urinary Na, normal urinary sediment, poor prognosis
Type 1 vs Type 2 hepatorenal syndrome
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Hepatopulmonary syndrome
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Hepatic encephalopathy
potentially reversible neuropsychiatric abnormality in setting of acute or chronic liver failure. Increased NH3 brain diffusion with edema is the cause
Clinical features of hepatic encephalopathy
spatial perception distortion, sleep disturbances, personatlity changes, asterixis, abnormal EEG, lethargy, coma, decerebrate posture.
Acute asymptomatic hepatitis infection with recover: serologic evidence only
Hep A, B most, C, D coninfection, E
Acute symptomatic hepatitis with recovery: anicteric or icteric
Hep A, B, C, D coinfection, E
Chronic hepatitis: without or with progression to cirrhosis
Hep B few, C 85%, D superinfection most
Fulminant hepatitis: with massive to submassive hepatic necrosis
Hep A rare, B rare, C rare, D co and super, E pregnant
Picorna virus-RNA, transmission is fecal oral, no carrier state or chronic hepatitis, rarely causes fulminant hepatitis. Clinical disease mild/asymptomatic and rare after childhood.
Hep A
Only dsDNA, hepadnavirus, most common cause of cirrhosis and hepatocellular carcinoma (background of cirrhosis needed), transmission via parenteral, sexual, vertical
Hep B
Chronic Hep B extrahepatic manifestations
Glomerulonephritis in children, polyarteritis nodosa in adults.
Hep D needs what other Hep to replicate
Hep D needs Hep B
Chronic Hep C extrahepatic manifestations
Cryoglobulinemia, thyroiditis, glomerulonephritis, thrombocytopenia
When is Hep E not benign
When you’re preggers
Primary biliary cirrhosis
Antimitochondrial antibody. Genetic predisposition. Get cirrhosis, gallstones, hepatocellular carcinoma. Liver failure over long period of time.
Diagnosis of primary biliary cirrhosis
Increased AMA, anti M2, anti PDH E2. Increased IgM, increased AP/5-NT/GGT, increased cholesterol
Primary sclerosing cholangitis diagnosis
Increased AP, GGT, 5-NT.
p ANCA positive in 80% of cases
Also do ERCP
PSC complications
Chronic cholestasis, cholangitis, secondary biliary ciffhosis, liver failure, cholangiocarcinoma.
Type I autoimmune hepatitis
SMA, ANA, most common
Type II autoimmune hep
Anti LKM1
Type III autoimmune hep
Anti SLA/LP
