Hepatocytes perform liver's metabolic functions

• Formation and excretion of bile
• Regulation of carbohydrate homeostasis
• Lipid synthesis and secretion of plasma lipoproteins
• Control of cholesterol metabolism
• Formation of serum albumin, clotting factors, enzymes, urea, and numerous other proteins
• Metabolism and detoxification of medications and other foreign substances
• Stores glycogen, iron, vitamins, and minerals

1. Secretes fluid-containing digestive enzymes into the duodenum
2. Secretes the hormones insulin and glucagon, which help regulate sugar levels in the bloodstream
3. Secretes into the duodenum large of quantities of Na⁺HCO₃^- needed to neutralize the acid coming from the stomach

Bile = bile salts, bilirubin, phospholipids, cholesterol, bicarbonate, and water

Emulsifies fat and fat-dependent vitamins (A,D,E,K) to promote absorption

1. Cholelithiasis = gallstones
2. Cholecystitis = inflammation of the gallbladder
3. Cholestasis = back up of bile in the liver

• Fatigue, weakness
• Nausea, poor appetite, weight loss
• Steatorrhea -- loose, fatty stool

• Spider angiomas
• Palmar erythema
• Pruritis
• Clubbing

• Tachycardia
• Hypotension
• Anemia
• Leukopenia
• Thrombocytopenia
• Coagulopathy

Amylase (N = 40-140 U/L)

• Released into blood when the pancreas is diseased, injured, or inflamed
• Non-specific alone -- used in combination with signs/symptoms

Lipase (N = 0-160 U/L)

• Released into the blood when the pancreas is diseased, injured, or inflamed
• Non-specific alone -- used in combination with signs/symptoms

• Aspartate transaminase (AST) = 5-43 IU/L
• Alanine transaminase (ALT) = 8-40 IU/L
• Enzymes located in the cytoplasm of hepatocytes
• Elevated with hepatocellular injury

High Levels (> 20x) = acute viral, drug-induced or ischemic

EtOH liver dz = rarely ALT > 500 IU/L

Moderate elevation (100-300 IU/L) = chronic liver dz

Ratio of AST:ALT > 2 = suggests alcoholic liver dz

AST can be elevated in rhabdomyolysis, heart damage, or brain tissue damage

• N = 85-285 IU/L
• Enzyme found in almost all body tissues and released when cells are damaged or destroyed
• Insensitive for hepatocellular injury -- but sensitive for cancers involving the liver
• Also indicates hemolysis, MI, or PE

Bilirubin

• Total bilirubin (N = < 1.2 mg/dL)
• Direct bilirubin (N = < 0.3 mg/dL)

Alkaline Phosphatase

• N = 30-115 IU/L
• cellular enzyme with high concentrations in the liver and bone
• Found in cells that join to form the bile ducts
• Elevated when bile flow through the bile duct is disrupted

Gamma-Glutamyl Transpeptidase

• N = < 50 IU/L
• Liver enzyme that is very sensitive to changes in liver function
• Levels of GGT correlate well with ALP
• Combination is sensitive and specific for biliary tract disease

Unconjugated Bilirubin

• Excessive production = hemolysis
• Immature enzyme system = Jaundice of newborn/ prematurity
• Inherited defects = Gilbert syndrome, Crigler-Najjar syndrome

Conjugated Bilirubin

Impaired Intrahepatic Excretion

• hepatocellular disease = hepatitis, cirrhosis, medications
• intrahepatic cholestasis = pregnancy, medications
• congenital = Dubin-Johnson syndrome, Rotor syndrome

Obstruction

• extrahepatic = calculus, stricture, neoplasm
• intrahepatic = sclerosing cholangitis, cirrhosis, neoplasm

PT/INR

• N = < 1
• Liver's ability to synthesize Vit-K depedent clotting factors (II, V, VII, X)
• Elevations indicate severe hepatocellular dysfunction and indicate progression to advanced cirrhosis

Serum Albumin

• N = 3.9-5
• Most abundant protein in the blood plasma
• Maintains oncotic pressure, nourishes tissues, and transports hormones, vitamins, drugs, and ions like Ca2+ throughout the body
• Synthesized in the liver and is extremely sensitive to liver damage
• Decreased levels with kidney disease, malnutrition, alcoholism, inflammation, and shock

• Quantifies effects of cirrhotic process
• Based on combination of clinical and laboratory data
• Used for drug-dosing adjustments
• Limitations = relies on subjective scoring for ascites and encephalopathy

Grade A (mild) = < 7 pts

Grade B (moderate) = 7-9 pts

Grade C (severe) = 10-15 pts

• The accepted classification system used by the United Network of Organ Sharing (UNOS)
• Used in the allocation of livers for transplant
• Relies solely on objective data
• Not currently used for medication dosing
• Score range from 6 (less ill) to 40 (gravely ill)

4 MELD Levels for organ allocation

> 25
24-19
18-11
< 10