Lab Evaluation for Liver Disease

Question 1

• Hepatic Artery (from Heart): low flow, high oxygen

- Portal Vein (from intestine): high blood flow; supply of nutrients from intestine; carries bactieral antigens

Answer 1

Liver Blood Supply

Question 2

Open pore capillaries that provide blood supply to hepatocytes

Answer 2

Sinusoids

Question 3

• join together to form bile ductules

Answer 3

Canaliculi

Question 4

specialized macrophages located in the liver lining the walls of the sinusoids that remove antibody-antigen complexes

Answer 4

Kupffer cells

Question 5

• normally store fat

- can transform to myofibroblasts, important in scar formation during liver damage

Answer 5

Stellate cells

Question 6

• detoxification: make lipid compounds soluble (e.g., bilirubin) to allow excretion
• Synthesize plasma proteins, including clotting factors
• Synthesize lipids, lipoproteins, and glucose
• Endocrine functions
• Ag-Ab complex removal (by Kupffer cells)

Answer 6

Liver functions

Question 7

1. RBCs are consumed by macrophages of the RES
2. Heme is broken down into Iron and Protoporphyrin
3. Protoporphyrin is converted to unconjugated bilirubin (fat-soluble)
4. Albumin carries UCB to the liver
5. UGT in hepatocytes conjugates bilirubin (glucuronic acid) –> water-soluble
6. CB is transferred to bile canaliculi to form bile, which is stored in the gallbladder
7. Bile is released into the small bowel to aid digestion
8. Intestinal flora convert CB to urobilinogen, which makes the stool brown
9. Urobilinogen is also partially reabsorbed into the blood and filtered by the kidney, making the urine yellow

Answer 7

Normal Bilirubin Metabolism

Question 8

• measures all forms of bilirubin

- uses “accelerant”, e.g., caffeine, methanol

Answer 8

Total Bilirubin Test

Question 9

• Detects conjugated bilirubin

- no accelerant

Answer 9

Direct Bilrubin Test

Question 10

• measures unconjugated bilirubin

- Total - direct bilirubin

Answer 10

Indirect Bilirubin Test

Question 11

• Measure for acute liver disease
• Synthesized by liver cells
• has short half-life (6 hours)

Answer 11

Factor VII / PT

Question 12

• Measure for chronic liver disease
• Synthesized by liver cells
• has long half-life (20 days)

Answer 12

Albumin

Question 13

• intermediate biomarker (1 day - 6 days)

Answer 13

Transthyretin / transferrin

Question 14

• hepatocyte: cytoplasmic & mitochondrial
• source: Liver, heart, muscle, kidney
• although ALT is more specific, AST is at higher levels within hepatocytes
• AST is cleared faster than ALT (18 hours)

Answer 14

AST

Question 15

• hepatocyte: cytoplasmic
• source: mostly liver (more specific than AST)
• serum half-life: 2 days

Answer 15

ALT

Question 16

• hepatocyte: cytoplasmic
• source: Liver, RBC, heart, muscle, all cells (non-specific)
• only tells you there is inflammation w/in the body
• serum half-life: 4-6 hours

Answer 16

LDH

Question 17

• hepatocyte: membrane-bound
• source: mostly liver & bone
• serum half-life: 24 hours
• abnormal levels usually due to obstruction of bile drainage from the liver

Answer 17

Alkaline Phosphatase

Question 18

• hepatocyte: membrane-bound

- source: mostly liver

Answer 18

GGT

Question 19

• serum tumor marker for hepatocellular carcinoma

- normal adult level is

Answer 19

alpha-fetoprotein

Question 20

• another sensitive tumor marker for hepatocellular carcinoma
• more specific than alpha-fetoprotein

Answer 20

DCP/PIVK-II

Question 21

• viral antibody tests only
• anti-HAV antibody develops after initial infection (or after immunization), and is protective for life
• IgM anti-HAV remains positive for only 6 months

Answer 21

HAV

Question 22

• viral antigen, antibody and nucleic acid tests available
• HBsAg: indicates active infection
• HBcAb: develops after natural infection; IgM lasts 3-6 months
• HBsAb: is protective for life; develops after recovery or after vaccination
• HB DNA: Indicates active infection; major test to monitor treatment

Answer 22

HBV

Question 23

• viral antibody and nucleic acid tests available
• anti-HCV antibody develops with exposure, but may not be detectable in acute phase; it is not protective, but remains positive for life
• HCV RNA is used to confirm active infection and monitor response to treatment

Answer 23

HCV

Question 24

Primary Biliary Cirrhosis

Answer 24

Anti-Mitochondrial Antibody

Question 25

Autoimmune Hepatitis

Answer 25

Anti-Actin (smooth muscle); Anti-Nuclear Antibody

Question 26

Sclerosing Cholangitis

Answer 26

Atypical p-ANCA

Question 27

- yellow discoloration of tissue due to excess bilirubin - typically accompanied by dark urine and pale stools (conj bilirubin is blocked from leaving liver to small intestine) - usually due to acute liver disease; late in chronic diseases

Answer 27

Jaundice (Icterus)

Question 28

- increased unconjugated bilirubin due to delayed function of metabolic enzymes

Answer 28

Physiologic Jaundice of Newborns

Question 29

- almost always due to liver or biliary tract disease

Answer 29

Conjugated bilirubin Jaundice

Question 30

- increased production - portal hypertension - Congenital disorders

Answer 30

Unconjugated bilirubin jaundice

Question 31

- mildly low UdpGT activity --> results in increased unconjugated bilirubin - autosomal recessive - causes jaundice during stress; otherwise, not clinically significant

Answer 31

Gilbert Syndrome

Question 32

- absence of UdpGT, resulting in high levels of unconjugated bilirubin - Clinical features: Kernicterus (fat soluble deposits in brain); usually fatal - Tx: liver transplant

Answer 32

Crigler Najjar Syndrome

Question 33

- Deficiency of bilirubin canalicular transport protein; autosomal recessive - results in buildup of conjugated bilirubin within hepatocytes, which leak into blood and cause jaundice - Liver is dark; otherwise, not clinically significant

Answer 33

Dubin-Johnson Syndrome