CC1_Finals_Lec: Liver Function Test

What are the major functions of the liver?

Metabolism of carbohydrates, lipids, proteins, and bilirubin; detoxification; storage of essential compounds; excretion of harmful substances

Largest and most versatile organ in the body

Liver

Location of the liver

Right upper quadrant beneath the diaphragm

Approximate percentage of liver that can regenerate after surgical removal

Approximately 80%

What happens after total liver loss?

Death from hypoglycemia within 24 hours

Blood supply received by the liver per minute

Approximately 1500 mL/min

Blood vessel supplying most oxygen to the liver

Hepatic artery

Percentage of liver blood supply from hepatic artery

25%

Blood vessel transporting absorbed nutrients from intestines to liver

Portal vein

Percentage of liver blood supply from portal vein

75%

Functional cells of the liver

Hepatocytes

Major macrophages of the liver

Kupffer cells

Functions of Kupffer cells

Phagocytosis, immune defense, secretion of interleukins and TNF

Cells responsible for collagen synthesis leading to fibrosis and cirrhosis

Stellate (Ito) cells

Cells involved in liver regeneration

Oval cells

Anatomical unit of the liver

Lobule

Three liver systems

Biochemical hepatocytic, hepatobiliary, reticuloendothelial

Liver process converting glycogen to glucose

Glycogenolysis

Liver process converting glucose to glycogen

Glycogenesis

Synthesis of glucose from non-carbohydrate sources

Gluconeogenesis

Conversion of lactate back to glucose

Cori cycle

Exceptions to proteins synthesized by the liver

Immunoglobulins and adult hemoglobin

Proteins synthesized by the liver

Acute phase reactants and coagulation proteins

Process involving transfer of amino groups

Transamination

Removal of amino groups from amino acids

Deamination

Primary organ for lipid metabolism

Liver

Percentage of cholesterol synthesized by the liver

80%

Fatty acids are catabolized into what?

Acetyl-CoA

Cholesterol is converted into what in the liver?

Primary bile acids

Function of bile acids

Act as detergents and emulsifiers of lipids

Storage forms in the liver

Glycogen, vitamins A/D/B12/E/K, iron

Cells responsible for phagocytosis in liver

Kupffer cells

What compounds are detoxified by the liver?

Steroid hormones, drugs, foreign compounds

Less toxic nitrogenous waste produced by the liver

Urea

Function of liver in circulation

Blood storage and mixing of portal/systemic blood

Main pigment of bile

Bilirubin

Components of bile

Bile acids, lecithin, cholesterol, bilirubin, electrolytes

Daily bile production

Approximately 3 L/day

Daily bile excretion

Approximately 1 L/day

Important role of bile

Lipid digestion and emulsification

First-pass effect

All GI-absorbed substances pass first through the liver

Bilirubin is produced from catabolism of what?

Heme portion of hemoglobin

Chief site of bilirubin degradation

Spleen

Other sites of bilirubin degradation

Bone marrow and liver

Enzyme converting heme to biliverdin

Heme oxygenase

Enzyme converting biliverdin to bilirubin

Biliverdin reductase

Carrier protein for unconjugated bilirubin

Albumin

Site of bilirubin conjugation

Rough endoplasmic reticulum of hepatocytes

Enzyme responsible for bilirubin conjugation

UDPGT (UDP-glucuronyl transferase)

Type of bilirubin that is water insoluble

Unconjugated bilirubin

Type of bilirubin that is water soluble

Conjugated bilirubin

Synonym of unconjugated bilirubin

Indirect bilirubin

Synonym of conjugated bilirubin

Direct bilirubin

Van den Bergh reaction of unconjugated bilirubin

Indirect reaction

Van den Bergh reaction of conjugated bilirubin

Direct reaction

Which bilirubin is lipid soluble?

Unconjugated bilirubin

Which bilirubin is excreted in urine?

Conjugated bilirubin

Normal total bilirubin range in adults

0.2–1.0 mg/dL

Normal conjugated bilirubin range

0.0–0.2 mg/dL

Normal unconjugated bilirubin range

0.2–0.8 mg/dL

What is delta bilirubin?

Conjugated bilirubin tightly bound to albumin

Characteristic of delta bilirubin

Long half-life

Clinical use of delta bilirubin

Monitoring decline of bilirubin after obstruction relief

Yellow discoloration of skin and sclera due to bilirubin

Jaundice

Another term for jaundice

Icterus

Serum bilirubin level where jaundice becomes visible

2 mg/dL

Type of jaundice due to excessive RBC destruction

Prehepatic jaundice

Characteristic bilirubin pattern in prehepatic jaundice

Increased B1 and urobilinogen; normal B2

Causes of prehepatic jaundice

Malaria, hemolytic anemia, erythroblastosis fetalis, incompatible transfusion

Type of jaundice due to hepatocyte damage

Hepatic jaundice

Characteristic bilirubin pattern in hepatic jaundice

Increased B1 and B2, dec. Urobilinogen, (+) Urine Bilirubin

Causes of hepatic jaundice

Viral hepatitis, cirrhosis, Gilbert syndrome, Crigler-Najjar syndrome

Type of jaundice caused by bile duct obstruction

Posthepatic jaundice

Characteristic bilirubin pattern in posthepatic jaundice

Increased B2; normal B1, decreased Urobilinogen, (+) Urine Bilirubin

Most common cause of posthepatic jaundice

Choledocholithiasis

Important enzymes elevated in biliary obstruction

ALP, GGT, LAP, 5'-nucleotidase

Gilbert syndrome is characterized by what type of bilirubin increase?

unconjugated hyperbilirubinemia

Defective enzyme gene in Gilbert syndrome

UGT1A1

Inheritance pattern of Crigler-Najjar type I

Autosomal recessive

Main defect in Crigler-Najjar type I

Absent UDPGT

Main bilirubin elevated in Crigler-Najjar syndrome

B1

Inheritance pattern of Crigler-Najjar type II

Autosomal dominant

Dubin-Johnson syndrome causes increase in which bilirubin?

Conjugated bilirubin (B2)

Characteristic feature of Dubin-Johnson syndrome

Hepatic pigmentation

Rotor syndrome differs from Dubin-Johnson syndrome how?

No hepatic pigmentation

Lucey-Driscoll syndrome

Circulating inhibitor of bilirubin conjugation

Clinical definition of cirrhosis

Scar tissue replacing healthy liver tissue

Progression toward cirrhosis (Shoty low diagram)

Fatty liver → fibrosis → cirrhosis

Types of cirrhosis based on nodules

Macronodular and micronodular

Iron overload disorder associated with cirrhosis

Hemochromatosis

Complication caused by blocked portal blood flow

Portal hypertension

Enlargement of spleen due to portal hypertension

Splenomegaly

Dilated veins in esophagus due to portal hypertension

Esophageal varices

Low albumin in cirrhosis

Hypoalbuminemia

Fluid accumulation in abdomen

Ascites

Characteristic globulin electrophoresis finding in cirrhosis

Beta-gamma bridging

Main immunoglobulin elevated in cirrhosis

IgA

Main enzymes elevated in hepatitis

ALT and AST

Hepatitis virus transmitted by fecal-oral route

HAV and HEV

Hepatitis virus transmitted through blood/body fluids

HBV, HCV, HDV