Lectures 17, 18: Intro to Liver and LFTs Flashcards
Liver functions
Excretion (biliubin, bile acids, drugs), immune function, growth factor, hormone production, hematopoiesis (fetal), synthesizes proteins (albumin, clotting factors), substrate metabolism, storage, metabolizes drugs
Signs of liver failure
Loss of clotting factors –> coagulopathy; impaired bilirubin clearance –> jaundice; impaired glucose mobilization –> hypoglycemia; impaired metabolite clearance/detox –> encephalopathy; altered blood flow regulation –> renal failure
Signs of liver failure (2)
Reduced clearance of bacteria from portal blood –> sepsis; decreased growth factor/albumin –> anemia, edema; altered metabolism of hormones –> feminization; obstruction to blood flow –> portal HTN
The endothelium within the sinusoid of the liver is…
Fenestrated
What two specialized cells are in the sinusoid?
Hepato-stellate cell encircling the microvasculature and the hepatocyte
Liver macrophage specialized cell
Hepatic Kupffer Cell
Bile is secreted through the
Canaliculi system
Liver bloods supply and implications; __________ pressure/___________ capacitance
Dual: 2/3 through portal vein, 1/3 through hepatic artery; low pO2, easy for areas near central vein to become hypoxic AND liver is RARELY infarcted; low pressure and high capacitance
What drains into the portal vein? (3)
Splenic, coronary, mesenteric
Examples of acute injury and significance for transplant
Tylenol, viral infection, idiopathic; may require transplant if severe, but if it resolves, liver will return to normal
Examples of chronic liver injury and significance for transplant
Viral infection, alcohol, obesity-related, autoimmune, metabolic overload, biliary obstruction; chronic liver injury is progressive and may be asymptomatic
Histology of cirrhosis
Nodules surrounded by fibrous tissue
Complications of cirrhosis (5)
Hepatic encephalopathy, ascities, portal HTN, hepatorenal syndrome, splenomegaly
What tests reveal injury to hepatocytes?
AST, ALT bili
What tests reveal injury to bile ducts?
Alkaline phosphatase, gammaGT, bili
Four classes of dx liver tests
Liver enzymes, liver function tests, general systemic tests, liver imaging
Liver enzymes tested
AST, ALT, Alk Phos, Bili
Liver function tests
Albumin, prothrombin time, platelets
General systemic tests
CBC, renal fxn tests (BUN/creatinine)
Signs of chronic liver disease (9)
Scleral icterus, spider angioma, glossitis, palmar erythema, digital clubbing, gynecomastia, excoriations (marks from itching), xanthelasma, ascites
What’s the most common cause of spider angiomata?
Pregnancy due to estrogen
Bilirubin must be greater than this level to cause jaundice…causes
2.5 mg/dL; increased bilirubin production, impaired hepatic handling, or benign
Two sources of bilirubin and %
Erythrocytes (80%); non-hemoglobin hemoproteins (myoglobin, cytochromes, catalases; 20%)
Describe bilirubin in plasma
Unconjugated (insoluble), albumin-bound, total bilirubin = 1-1.5 mg/dL
Four steps of bilirubin (blood to bile)
- Hepatocellular uptake; 2. Intracellular binding; 3. Conjugation; 4. Excretion into bile canaliculus via MRP2 (multidrug resistance-associated protein 2)
Does bilirubin enter the hepatocyte alone or with albumin?
Alone
Enzymes of bilirubin conjugation
UGT = bilirubin-UDP-glucuronosyltransferase
Injury to the hepatocyte tends to affect with step of the bilirubin?
Liver can conjugate but NOT EXCRETE bilirubin (MRP2 is impaired) –> CONJUGATED bilirubin backs up into sinusoid –> central venule –> systemic circulation
Why is stool/urine the color it is?
Yellow urobilinogen (gets turned into brown stercobilin in colon)
Bilirubin + intestine
In ileum/colon, unconjugated and reduced to urobilinogen –> 80% feces, 15% absorbed and re-excreted as bile, 5% excreted in urine
Bilirubin + kidney
Conjugated bilirubin is filtered at glomerulus; with hepatobiliary dysfunction, conjugated bilirubin gets into kidneys –> darker urine
Causes of unconjugated hyperbilirubinemia (3)
- Increased production of bilirubin, 2. Reduced hepatic clearance of bilirubin, 3. Inherited disorders
Causes of increased production of bilirubin
Hemolysis, hematomas, ineffective erthropoiesis
Causes of reduced hepatic clearance of bilirubin
Neonatal jaundice (due to hepatic immaturity, tx w/ phototherapy), breast milk jaundice (maternal progestational steroids inhibit conjugation), drugs (antibiotics)
Inherited disorders of bilirubin conjugation (3)
Gilbert’s syndrome, Crigler-Najjar type I and type II
Describe Gilbert’s syndrome: frequency and %, symptoms, histology, gene, and enzyme activity
Most common hereditary hyperbilirubinemias (7%), asymptomatic but aggrevated by stress, no histological changes, UGT1A1 gene mutation, 10-33% of normal enzyme activity
Describe Crigler-Najjar Syndrome type I: mutation, enzyme activity, when it presents and complication, tx
Mutation in UGT1, no functional enzyme activity, appears neonataly, severe neurological impairment, fatal w/out transplant
Describe Crigler-Najjar Syndrome type II: mutation, enzyme activity, tx
Mutation of UGT1A1, reduced but detectable enzyme activity, tx = phenobarbital to induce UGT
Conjugated hyperbilirubinemia diseases (5 classes)
Genetic, chronic liver disease (cirrhosis), biliary obstruction, intrahepatic cholestasis of pregnancy, drug-induced cholestasis
Genetic causes of conjugated hyperbilirubinemia diseases (3)
- Dubin-Johnson syndrome, 2. Rotor syndrome, 3. Familial Cholestasis syndromes
Describe Dubin-Johnson syndrome: mutation and presentation
Mutation in MRP2 with chronic intermittent jaundice and pigmented liver, scleral icterus, enlarged liver
Describe Rotor syndrome
High total bilirubin with normal life expectancy (unknown mutation, not much known)
Causes of biliary obstruction
Choledocholithaisis, neoplasms, extrinsic compression of biliary tree, inflammation/infection
Describe intrahepatic cholestasis of pregnancy: when in pregnancy, lab tests, does it go away?
2nd/3rd trimester, elevated ALT, bilirubin, bile acids; generally disappears after delivery but may reappear with other preg/estrogens
Three most common scenarios of acute hepatocellular inury and LFTs
Ischemic injury (“shock liver” = trauma), drug-induced liver failure, acute viral hepatitis; elevated ALT, AST, some bilirubin, all else likely normal
Five most common scenarios of chronic liver disease/cholestatic liver disease
Chronic viral hepatitis, NAFLD, alcoholic hepatitis, cirrhosis, biliary obstruction
Cirrhosis: LFTs
ALT, AST, Alk Phos, GGTP, Bilirubin NORMAL or slightly elevated; elevated prothrombin time, low albumin
Biliary obstruction: LFTs
ELEVATED Alk Phos, GGTP, bilirubin; normal or slightly elevated ALT, AST, fxn tests
Chronic viral hepatitis and NAFLD: LFTs
Elevated ALT, AST, normal or slightly elevated cholestasis, normal fxn tests
Alcoholic hepatits: LFTs
Elevated AST > ALT (specific to alcoholic), elevated cholestasis, normal fxn tests
