The Liver

Loss of liver will result death within 24 hours due to _________________

hypoglycemia

Liver lobules are made up of (3)

hepatic artery

portal vein

bile duct

Sinusoids are ________________ spaces between the cords of the liver cells

vascular

_______________ cells line the sinusoids and work to remove bacteria and other particles from the blood

Kupffer

_________________ are conduits between the hepatocytes. They join together to form larger bile ducts until a common bile duct is reached.

Canaliculi

Bile helps with _______ digestion

fat

Bile is created by the (1), stored in the (2), and ejected into the (3)

liver; gall bladder; small intestine

Flow of blood in the liver (4)

sinusoids → central veins → hepatic veins → inferior vena cava

The liver makes _______________

proteins

Bilirubin conjugation uses (1) acid and the enzyme (2)

glucuronic; UDP-glucuronyltransferase

_____________ is the main bile pigment

Bilirubin

Bilirubin is produced from the destruction of _________, from spleen. bone marrow, and liver.

RBCs

Bilirubin is mostly derived from hemoglobin degradation (80%), while the rest comes from other heme-containing components such as (3)

myoglobin

cytochrome

catalase

Flow of bilirubin synthesis

Hgb → verdohemoglobin → biliverdin + Fe +globin → bilirubin

Fractions of bilirubin (3)

unconjugated

conjugated

delta (RARE)

Unconjugated bilirubin is nonpolar, water-INsoluble, and bound to ______________

albumin

Unconjugated bilirubin will only react with _________________________________ solution in the presence of an accelerator (such as caffeine)

diazotized sulfanilic acid

Conjugated bilirubin is polar, water-soluble, and will react with diazotized sulfanilic acid ______________.

directly

Delta bilirubin s seen only in ________________ obstruction, and remains elevated long after the obstruction has cleared.

hepatic

Conjugated bilirubin is also known as bilirubin _____________________

diglucuronide

Enzyme used to conjugated bilirubin:

UDP-glucuronyl transferase

Normal conditions: (high/low) concentration of bilirubin in serum, majority is _____________

low, unconjugated

Bacteria in the small intestines act on (1) bilirubin to produce (2)

conjugated; urobilinogen

Urobilinogen created in the SI exits the SI via ________ veins, re-enters the blood, and is excreted through the kidney.

portal

Oxidation of urobilinogen produces ____________, a red-brown color excreted in the stool

urobilin

Jaundice: yellow staining of (3 things) due to elevated bilirubin

skin

sclerae

mucus membranes

Kernicterus: brain damage from high bilirubin in _____________ blood

infant

Icteric: short term for ____________

jaundice

Bilirubin in the urine indicates an increase in _____________ bilirubin, and is ALWAYS pathogenic

conjugated

Liver enzymes used in diagnosis (6)

AST

ALT

ALP

GGT

5NT

LD5

AST (aka SGOT) catalyzes transfer of amino group between (1) and (2), and elevates rapidly at the BEGINNING of disease

aspartate; alpha-keto acids

Normal range for AST:

5-30 U/L

Most specific enzyme for liver disease:

ALT (alanine aminotransferase)

ALT (aka SGPT) catalyzes an amino group transfer to form (1) and (2)

glutamate; pyruvate

Normal range for ALT

6-37 U/L

(T/F) In diseased states, AST is 2.5 times higher than ALT in the liver

FALSE

Normal: AST is 2.5x higher than ALT

Diseased: ALT elevates as high or higher than AST

GGT is ___________ in hepatocellular and obstructive disorders, but is NOT specific for any type of liver disease

increased

__________ is used as a screening test for alcohol abuse

GGT

Normal ranges for GGT (male vs female)

male: 6-45 U/L

female: 5-30 U/L

ALP (alkaline phosphatase) is associated with canalicular membrane damage or _____________________________

biliary obstruction

Normal range for ALP

30-90 U/L

5NT is a phosphatase used to determine whether the elevation of ________ is caused by liver or bone disease

ALP

5NT, along with GGP, is used as a marker for _______________________

alcohol abuse

Bone disease: (high/low) ALP, ___________ 5NT

high; normal

Liver disease: (high/low ALP), (high/low) 5NT

high; high

Normal range of 5NT

3-9 U/L

LD5 is an ______________ indicative of liver disease

isoenzyme

Normal range of LD5

6-16 %

Liver proteins (3)

albumin

coagulation factors

immunoglobulins

______________ albumin is indicative of CHRONIC liver disease

decreased

Prothrombin time (PT) test measures the _____________ dependent factors in a pathway

Vitamin K

_____________ in PT indicative of ACUTE liver disease

increase

________________ in immunoglobulins indicative of CHRONIC liver disease

increase

High IgA indicates

alcoholic liver disease

High IgG indicates

autoimmune hepatitis

High IgM indicates

primary biliary cirrhosis

Decreased _______________ → Wilson’s disease

ceruloplasmin

Decreased ____________________ → cirrhosis

alpha-1 antitrypsin

Greatly increased ________________ → primary hepatocellular carcinoma

AFP (alpha fetoprotein)

INCREASED unconjugated bilirubin causes (2)

increased hemolysis

decreased conjugation

Hepatic disorders of newborn (2)

Neonatal jaundice (peaks after 4-5 days)

Pathological jaundice (past 10 days)

Most common causes of pathological jaundice in infants (2)

HDFN (hemolytic disease of the fetus and newborn)

sepsis

Pre-hepatic disorders have an increase in ______________ bilirubin; acute/chronic hemolytic anemias

unconjugated

Hemolytic anemias will NOT present with bilirubin in the ____________

urine

Acute hepatitis is primarily caused by _________ or toxins

virus

Common causes of hepatitis (6)

HepA

HepB

HepC

EBV

alcohol

fungal toxins

Acute hepatitis: (high/low) urine bilirubin, (high/low) urobilinogen

high; high

Chronic hepatitis: lasting longer than _____ months

6

Common causes of chronic hepatitis (3)

autoimmune hepatitis

HepB

HepC

Cirrhosis: death and regeneration of liver cells leads to _________ in the liver

scarring

Common causes of liver cirrhosis (3)

chronic alcohol consumption

autoimmune hepatitis

viral hepatitis

Detection of _______________________ used to monitor development of cirrhosis

procollagen type 3 peptide

Ethanol effects on liver (3)

hepatic steatosis (fatty liver disease)

alcoholic hepatitis

cirrhosis

A non-alcoholic cause for fatty liver disease is excessive ________________ consumption

fructose

Inherited hepatic disorders (4)

Gilbert’s Disease (increase conj.)

Crigler-Najjar (increase conj.)

Dubin-Johnson (increase unconj.)

Rotor (increase unconj.)

Gilbert’s Disease characteristics

increased unconjugated

normal conjugated

defect in UDPGT, mild, impaired cellular

Crigler-Najjar syndrome

increased unconjugated

decreased conjugated

defect in UDPGT

type I- no enzyme activity

type II- partial enzyme activity

Dubin-Johnson

increased conjugated

normal unconjugated

deficient secretion into bile canaliculi; dark granules in liver

Rotor syndrome

increased conjugated

normal unconjugated

cause unknown; no dark granules in liver

Wilson’s disease is characterized by ____________ deposits in tissues, due to low ceruloplasmin

copper

Post-hepatic disorders have _______________ levels of all kinds of bilirubin

increased

Jendrassik-Grof total bilirubin test measures absorbance at ____________ nm

340

Normal ranges for bilirubin (infants & adults)

infants: 2-6 mg/dL

adults: 0.2-1.0 mg/dL

indirect: 0.2-0.8 mg/dL

direct: 0-0.2 mg/dL

Jendrassik-Grof tests must be protected from _______

light

Base reagent of Jendrassik-Grof

diazotized sulfanilic acid

Addition of diazotized sulfanilic acid to bilirubin, sodium acetate, and caffeine benzoate produces:

purple azobilirubin

_____________ acts as an accelerator in the Jendrassik-Grof test

caffeine

After adding _________________________ to both tubes in the Jendrassik-Grof test, measure to color change at 600nm

alkaline tartrate

Evelyn-Malloy bilirubin test uses _____________ instead of caffeine as an accelerant

methanol

Urobilinogen is also known as (2)

stercobilinogen

mesobilinogen

Addition of urobilinogen to ______________________ produces a RED colored complex

p-methyl aminobenzaldehyde

Normal range of urobilinogen

0\.1-1.0 Ehrlich units/2hr