The LiverJustin Harris OMS IV

Outline

• Anatomy

• Histology

• Physiology

• Liver Function Tests

• Pathophysiology

Anatomy• Blood supply

– Dual blood supply

– Portal Vein 75% blood supply (oxygen poor & nutrient rich)

– Hepatic Artery 25% blood supply (oxygen rich)

• Couinaud schemaGallbladder is between IV & V

Histology

• Liver Acinus

– Zone 1

• First to show bile duct occlusion changes

• First to regenerate

• Last to die from is-chemia

– Zone 2

– Zone 3

• First to show centrilobu-lar necrosis 2* to is-chemia with decreased CO

Reticuloendothelial Function

• Kupffer cells

– Make up 80-90% of fixed macrophages in the body reside within the liver sinusoidal lumen

• Ito/Stellate Cells

– Appear to be regulators of hepatocyte and endothelial cell function

– Activated in states of liver injury and increase fibrosis due to inhibition of apoptosis

Protein Synthesis

• Plasma Proteins

– Albumin

• ~10g/day are made (1/2 life is 22 days)

– Transferrin, haptoglobin, fer-ritin, hemopexin, & cerulo-plasmin

– Coagulation Factors

• Hepatocytes synthesize all clotting factors except VIII (synthesized by vascu-lar endothelium)

Drug Metabolism• Xenobiotics=> drugs/toxins not used in

normal metabolic pathways to maintain the integrity of a cell or tissue

• Phase I

– Oxidation, Reduction, Hydrolysis

– Cytochrome P450

• Phase II

– Conjugation

Hepatocyte Bile Formation

• Bile

– Bile Salts

– Phospholipids

– Conjugated Bilirubin

– Cholesterol

• Bile facilitates intestinal absorption of lipids and fat soluble vitamins

• Increase bile secretion

– Vagal stimulation, CCK, Gastrin, Glucagon

Liver Function Tests• Synthetic Function

– Albumin & Prothrombin Time

• Hepatocyte Injury

– AST

– ALT

• Secretory Function

– ALP

– GGT

– Bilirubin

• Cirrhosis

• Characterized by destruction of hepatic parenchyma

– Replacement by fibrosis and regenerative nodules

• Causes:ETOH, Viral infections (Hep B&C), biliary obstruction, etc.

• Prognostic Tests

• MELD Score

• MELD= 3.78(serum bilirubin)+11.2(INR)+9.57(serum creatinine)+6.43

• Child-Turcotte-Pugh Classification

Hepatic Pathophysiology

Portal Hypertension

• Normal portal venous pres-sure (5-10mm Hg)

• Obstruction increases portal vein pressure and increases blood flow to the heart through collateral vessels

• Hallmark of Portal Hyper-tension

– Decreased intrahepatic NO

– Increased splanchnic NO

Acute Liver Failure

• Sudden loss of liver metabolic functions resulting in coagulopathy and encephalopathy

• Coagulopathy and acidosis are common = poor prognosis

• Hypoglycemia 2* to impaired gluconeogenesis in the liver

• Systemic hypotension may occur, even if there is a high CO, because of low SVR.

Summary

• Anatomy

• Histology

• Physiology

• Liver Function Tests

• Pathophysiology