Chem II Unit #1

Functions of LIver

metabolism, synthesis, detox, excretion/secretion, storage

Hepatic artery

25% of blood in liver. Branch of aorta and oxygen rich

Hepatic Portal Vein

75% of blood in liver. Drains digestive tract and is nutrient rich

Portal Vein Sources

stomach, spleen, pancreas, and small intestine

Stomach

metabolizes/detoxes drugs alcohols

Spleen

bilirubin is conjugated and excreted. Iron is stored/redistributed

Pancreas

insulin/glucagon regulate glucose metabolism

Small Intestine

monosacchardies, ammonia, drugs/toxins, and microbial products

Lobule

functional unit of liver. hexagonal.

Portal Triad

bile duct, branch of portal vein, branch of hepatic artery

Central Vein

leads out to hepatic vein to inferior vena cava

Portal vein and hepatic artery —> sinusoid —> central vein —> hepatic vein —> inferior vena cava

Lobule Blood Flow

Kupffer Cells

macrophages lining sinusoids

Bile Canaliculi —> intrahepatic duct —> right/left hepatic duct —> common hepatic duct —> common bile duct —> duodenum

Lobule bile flow

Glucose-6-phosphate

glycogen turns into this and G6Pase turns it into glucose

AA Pool

small continually changing supply of free AA

Transamination

transfer amino group to another carbon skeleton

Deamination

remove amino group creating free NH3

First Pass Metabolism

describes metabolism of oral drugs before they reach systemic circulation, which may reduce bioavailability compared with other routes

Resevoir Function

stores glycogen, vitamin, iron, copper, trig

Secretion

release of bile acid for digestion/absorption of lipid

Excretion

removal of waste or excess substances (conjugated bili, exces chol, drugs)

Bilirubin

most gets eliminated as stercobilin. Most circulating blood is unconjugated

Direct Bilirubin

conjugated. directly measured

Indirect bilirubin

unconjugated. measured by total - direct

Total Bilirubin

direct bilirubin and indirect bilirubin together. Measured

Unconjugated bilirubin

Indirect. water insoluble, nonpolar. Transported bound to albumin. Calculated

Conjugated Bilirubin

Direct. water soluble, polar. free in plasma. appears in urine when elevated in plasma

Jaundice

yellow skin, sclera, mucous membrane

Hyperbilirubinemia

retention of bilirubin

Icterus

dark yellow plasma or serum

Kernicterus

permanent neurological damage resulting from unconjugated bilirubin during infancy

Prehepatic (Hemolytic Jaundice)

Increased unconj bili. No bilirubinuria

Hepatic (Heptaocellular Jaundice)

problem affecting the liver, broken into hepatic uptake problem or bili transport problem

Hepatic Uptake/Conjugation Problem

increased unconjugated and no bilirubinuria

Bili Transport Problem

Increased conjugated. Bilirubinuria

Posthepatic (Obstructive Jaundice)

biliary obstruction caused by inflammation, scar, gallstone, etc. Chalky pale stool. Increased conjugated bili and bilirubinuria

Gilbert Syndrome

intermittent unconj hyperbilirubinemia. Caused by UGT1A1 mutation. No clinical consequence

Crigler-Najjar Syndrome Type 1

Complete absence of UGT1A1

Crigler-Najjar Syndrome Type 2

severe enzyme deficiency of UGT1A1

Neonatal Jaundice

immature UGT1A1 activity at birth. Unbound bili may enter brain and cause kernicterus

Phototherapy

converts unconj bili into water soluble photoisomers

Exchange Transfusion

for bili at the exchange threshold or sings of acute bili encephalopathy

Dubin-Johnson Syndrome

MRP2 (transporter protein) deficiency. Excretion into bile is defective. Causes black liver

Rotor Syndrome

mutations affecting OATP1B1 and OATP1B3. Transport conj bili from blood into hepatocytes on 2nd pass

Steatosis

fat accumulation in hepatocytes

Hepatitis

liver inflammation and hepatocyte injury

Steatohepatitis

steatosis with inflammation and injury

Fibrosis

buildup of scar tissue after ongoing injury

Regenerative Nodules

clusters of regenerative hepatocytes surrounded by scar tissue

Cirrhosis

advanced fibrosis and regenerative nodules that distort liver structure and blood flow

Cholestasis

reduced or blocked bile flow

Portal Hypertension

increased pressure in the portal venous system caused by distorted tissue blocking flow

Liver Injury

normal or mildly increased liver enzymes

Poor Liver function

increased bili, increased ammonia, decreased albumin, increased PT/INR, increased GGT (alcohol)

Early Indicator of Portal Hypertension

decreased plt due to TPO syn being sequestered

Hemochromatosis

iron disorder causing cirrhosis

Wilson Disease

copper disorder causing cirrhosis

Alpha1 Antitrypsin deficiency

misfolded alpha1 antitrypsin causing cirrhosis

Primary Liver Tumors

begin in hepatic or biliary cells. usually with cirhosis or chronic hep B/C

Metastatic Tumors

90-95% much more common than primary liver tumors

Reye Syndrome

rare acute encephelopathy and fatty liver injury in children. usually following viral illness. Increased ammonia and AST/ALT

Intrinsic DILI

predictable and dose related, as with acetaminophen

Idiosyncratic DILI

unpredictable and patient-specific

Transcutaneous Bilirubin (TcB)

noninvasive estimate from light reflected by skin. screens newborns for hyperbilirubinemia

Diazo Reaction

bili + diazotized sulfanilic acid = colored azobilirubin

Malloy-Evelyn

uses methanol as accelerator and produces red-purple product

Jendrassik-Grof

Reference method. uses caffeine-benzoate as accelerator and ascrobic acid to stop rxn. Shifts to blue

Ehrlichs Reagent

red color. tests for urine urobiliogen

ALT

released with hepatocyte injury. Liver specific

AST

released with heaptocyte injury. Found in liver, muscle, RBC

ALP

increases with most cholestasis. Increased during hepatic obstruction. Produced by bone, placenta, intestine

GGT

increased during alcohol and some drugs. increases with cholestasis and hepatobiliary injury

Hepatitis A

nonenveloped RNA. incubates 2-6 wk. Self-limited. Two-dose vaccine

IgM Anti-HAV

acute infection

IgG Anti-HAV

past infection or vaccine

Hepattis E

noneveloped RNA. fecal - oral. incubates 3-6 wk. Devestating in pregnant women

Hepatitis C

enveloped RNA. parenteral. acute infection or asymptomatic, no vaccine

Anti-HCV

ab appears late and is not protective, ab alone does not show infection. Confrim with HCV RNA by RT-PCR

Hepatits D

defective enveloped RNA (satellite virus requires HBsAg)

Coinfection

acquired with HBV

Superinfection

acquired after HBV infection (70-90% become chronic)

Hepatitis B

envoloped DNA. incubates 8 - 26 wk. parenteral, perinatal, sexual. survives on surfaces 7 days. Vaccine preventable

HBsAg

first marker to appeaer in HBV. persistence past 6 months is chronic

Anti-HBs

recovery or vaccine immunity. protective level is 10 or greater

HBcAg

found only in hepatocyte nuclei in HBV

Anti-HBc

appears before anti-HBs. IgM confirms acute infection

HBeAg

marker of active replication correlates with viral load. persistence is more than 3 months

Anti-HBe

indicates low infectivity, suggests improved prognosis and reduced liver damage

Early acute infection

HBsAg only

Vaccinated

Anti-HBs alone

Acute Infection

HBsAg and IgM Anti-HBc

Recovered and Immune

Anti-HBc and Anti-HBs