Lectures 17, 18: Intro to Liver and LFTs

Question 1

Liver functions

Answer 1

Excretion (biliubin, bile acids, drugs), immune function, growth factor, hormone production, hematopoiesis (fetal), synthesizes proteins (albumin, clotting factors), substrate metabolism, storage, metabolizes drugs

Question 2

Signs of liver failure

Answer 2

Loss of clotting factors –> coagulopathy; impaired bilirubin clearance –> jaundice; impaired glucose mobilization –> hypoglycemia; impaired metabolite clearance/detox –> encephalopathy; altered blood flow regulation –> renal failure

Question 3

Signs of liver failure (2)

Answer 3

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

Question 4

The endothelium within the sinusoid of the liver is…

Answer 4

Fenestrated

Question 5

What two specialized cells are in the sinusoid?

Answer 5

Hepato-stellate cell encircling the microvasculature and the hepatocyte

Question 6

Liver macrophage specialized cell

Answer 6

Hepatic Kupffer Cell

Question 7

Bile is secreted through the

Answer 7

Canaliculi system

Question 8

Liver bloods supply and implications; __________ pressure/___________ capacitance

Answer 8

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

Question 9

What drains into the portal vein? (3)

Answer 9

Splenic, coronary, mesenteric

Question 10

Examples of acute injury and significance for transplant

Answer 10

Tylenol, viral infection, idiopathic; may require transplant if severe, but if it resolves, liver will return to normal

Question 11

Examples of chronic liver injury and significance for transplant

Answer 11

Viral infection, alcohol, obesity-related, autoimmune, metabolic overload, biliary obstruction; chronic liver injury is progressive and may be asymptomatic

Question 12

Histology of cirrhosis

Answer 12

Nodules surrounded by fibrous tissue

Question 13

Complications of cirrhosis (5)

Answer 13

Hepatic encephalopathy, ascities, portal HTN, hepatorenal syndrome, splenomegaly

Question 14

What tests reveal injury to hepatocytes?

Answer 14

AST, ALT bili

Question 15

What tests reveal injury to bile ducts?

Answer 15

Alkaline phosphatase, gammaGT, bili

Question 16

Four classes of dx liver tests

Answer 16

Liver enzymes, liver function tests, general systemic tests, liver imaging

Question 17

Liver enzymes tested

Answer 17

AST, ALT, Alk Phos, Bili

Question 18

Liver function tests

Answer 18

Albumin, prothrombin time, platelets

Question 19

General systemic tests

Answer 19

CBC, renal fxn tests (BUN/creatinine)

Question 20

Signs of chronic liver disease (9)

Answer 20

Scleral icterus, spider angioma, glossitis, palmar erythema, digital clubbing, gynecomastia, excoriations (marks from itching), xanthelasma, ascites

Question 21

What’s the most common cause of spider angiomata?

Answer 21

Pregnancy due to estrogen

Question 22

Bilirubin must be greater than this level to cause jaundice…causes

Answer 22

2.5 mg/dL; increased bilirubin production, impaired hepatic handling, or benign

Question 23

Two sources of bilirubin and %

Answer 23

Erythrocytes (80%); non-hemoglobin hemoproteins (myoglobin, cytochromes, catalases; 20%)

Question 24

Describe bilirubin in plasma

Answer 24

Unconjugated (insoluble), albumin-bound, total bilirubin = 1-1.5 mg/dL

Question 25

Four steps of bilirubin (blood to bile)

Answer 25

1. Hepatocellular uptake; 2. Intracellular binding; 3. Conjugation; 4. Excretion into bile canaliculus via MRP2 (multidrug resistance-associated protein 2)

Question 26

Does bilirubin enter the hepatocyte alone or with albumin?

Answer 26

Alone

Question 27

Enzymes of bilirubin conjugation

Answer 27

UGT = bilirubin-UDP-glucuronosyltransferase

Question 28

Injury to the hepatocyte tends to affect with step of the bilirubin?

Answer 28

Liver can conjugate but NOT EXCRETE bilirubin (MRP2 is impaired) --> CONJUGATED bilirubin backs up into sinusoid --> central venule --> systemic circulation

Question 29

Why is stool/urine the color it is?

Answer 29

Yellow urobilinogen (gets turned into brown stercobilin in colon)

Question 30

Bilirubin + intestine

Answer 30

In ileum/colon, unconjugated and reduced to urobilinogen --> 80% feces, 15% absorbed and re-excreted as bile, 5% excreted in urine

Question 31

Bilirubin + kidney

Answer 31

Conjugated bilirubin is filtered at glomerulus; with hepatobiliary dysfunction, conjugated bilirubin gets into kidneys --> darker urine

Question 32

Causes of unconjugated hyperbilirubinemia (3)

Answer 32

1. Increased production of bilirubin, 2. Reduced hepatic clearance of bilirubin, 3. Inherited disorders

Question 33

Causes of increased production of bilirubin

Answer 33

Hemolysis, hematomas, ineffective erthropoiesis

Question 34

Causes of reduced hepatic clearance of bilirubin

Answer 34

Neonatal jaundice (due to hepatic immaturity, tx w/ phototherapy), breast milk jaundice (maternal progestational steroids inhibit conjugation), drugs (antibiotics)

Question 35

Inherited disorders of bilirubin conjugation (3)

Answer 35

Gilbert's syndrome, Crigler-Najjar type I and type II

Question 36

Describe Gilbert's syndrome: frequency and %, symptoms, histology, gene, and enzyme activity

Answer 36

Most common hereditary hyperbilirubinemias (7%), asymptomatic but aggrevated by stress, no histological changes, UGT1A1 gene mutation, 10-33% of normal enzyme activity

Question 37

Describe Crigler-Najjar Syndrome type I: mutation, enzyme activity, when it presents and complication, tx

Answer 37

Mutation in UGT1, no functional enzyme activity, appears neonataly, severe neurological impairment, fatal w/out transplant

Question 38

Describe Crigler-Najjar Syndrome type II: mutation, enzyme activity, tx

Answer 38

Mutation of UGT1A1, reduced but detectable enzyme activity, tx = phenobarbital to induce UGT

Question 39

Conjugated hyperbilirubinemia diseases (5 classes)

Answer 39

Genetic, chronic liver disease (cirrhosis), biliary obstruction, intrahepatic cholestasis of pregnancy, drug-induced cholestasis

Question 40

Genetic causes of conjugated hyperbilirubinemia diseases (3)

Answer 40

1. Dubin-Johnson syndrome, 2. Rotor syndrome, 3. Familial Cholestasis syndromes

Question 41

Describe Dubin-Johnson syndrome: mutation and presentation

Answer 41

Mutation in MRP2 with chronic intermittent jaundice and pigmented liver, scleral icterus, enlarged liver

Question 42

Describe Rotor syndrome

Answer 42

High total bilirubin with normal life expectancy (unknown mutation, not much known)

Question 43

Causes of biliary obstruction

Answer 43

Choledocholithaisis, neoplasms, extrinsic compression of biliary tree, inflammation/infection

Question 44

Describe intrahepatic cholestasis of pregnancy: when in pregnancy, lab tests, does it go away?

Answer 44

2nd/3rd trimester, elevated ALT, bilirubin, bile acids; generally disappears after delivery but may reappear with other preg/estrogens

Question 45

Three most common scenarios of acute hepatocellular inury and LFTs

Answer 45

Ischemic injury ("shock liver" = trauma), drug-induced liver failure, acute viral hepatitis; elevated ALT, AST, some bilirubin, all else likely normal

Question 46

Five most common scenarios of chronic liver disease/cholestatic liver disease

Answer 46

Chronic viral hepatitis, NAFLD, alcoholic hepatitis, cirrhosis, biliary obstruction

Question 47

Cirrhosis: LFTs

Answer 47

ALT, AST, Alk Phos, GGTP, Bilirubin NORMAL or slightly elevated; elevated prothrombin time, low albumin

Question 48

Biliary obstruction: LFTs

Answer 48

ELEVATED Alk Phos, GGTP, bilirubin; normal or slightly elevated ALT, AST, fxn tests

Question 49

Chronic viral hepatitis and NAFLD: LFTs

Answer 49

Elevated ALT, AST, normal or slightly elevated cholestasis, normal fxn tests

Question 50

Alcoholic hepatits: LFTs

Answer 50

Elevated AST > ALT (specific to alcoholic), elevated cholestasis, normal fxn tests