Normal Anatomy

• falciform ligament divides into two lobes (right lobe is larger)
• dual afferent blood supply – hepatic artery and portal vein
• 60-70% of blood supply comes from portal vein
• single venous drainage system

Histology and Metabolism

• Classic lobules – central vein surrounded by hepatocytes with portal tracts (hepatic artery, portal vein, and bile duct) at periphery
• ACINUS

Ø  Afferent vessels – center of the acinus

Ø  Central veins at the periphery

Ø  3 zones – zone 1 closest to the afferent vessels; zone 3 farthest

Ø  Zone 1 – primary site of gluconeogenesis

Ø  Zone 3 – primary site of glycolysis and drug detox.

Ø  Normal Cytoplasmic Inclusions – glycogen, no fat or iron, lipofuscin

General Pathologic Changes

Balooning Necrosis

• Hydropic change leads to swelling and eventually the cells burst

Eosinophilic Necrosis

• 2 separate mechanisms

1)     coagulative necrosis – slower process than balooning necrosis

2)     Apoptosis – nucleus undergoes karyolysis and the hepatocyte puts out bulbous eosinophilic buds; the cells just “fall apart”

Abnormal Inclusions

• Fatty Metamorphosis

Ø  macrovesicular fatty metamorphosis

v  single large fat droplet that pushes the nucleus to the side

v  more common form

v  2^o to nutritional deficiency, EtOH abuse

Ø  Microvesicular fatty metamorphosis

v  Foamy hepatocytes from multiple tiney fat droplets

v  Nucleus stays in a central location

v  Occurs in: fatty metamorphosis of pregnancy, tetracycline toxicity, Reye’s syndrome. Diabetes

• Mallory’s hyaline

Ø  eosinophilic cytoplasmic inclusions composed 1^o of the intermediate filaments of the cytoskeleton of the hepatocyte.

• Iron accumulation

Ø  toxic to hepatocytes (usually zone 1)

• Bile

Ø  toxic to cells = hydropic change

• Glycogen storage diseases
• Alpha-1-antitrypsin deficiency

Biliary Tree

Normal Anatomy

• canaliculi are the infolding of the adjacent hepatocytes
• peristaltic waves from the microvilli help move the bile
• the only time you see canaliculi are in pathological conditions where the bile stasis occurs
• canaliculiÞ bile ductules (canals of Herring)Þ bile ducts (epithelium becomes more columnar)

Cholangitis = inflammation and destruction of ducts

• Suppurative cholangitis

Ø  occlusion of flow dowstream causes stasis of bile and cause necrosis and inflammation

Ø  Infection 2^o to obstruction is major concern

• Non-suppurative cholangitis

Ø  auto-immune destruction of the bile ducts

Ø  prototypical form of this disease – primary ciliary cirrhosis

Vascular system of the Liver

Normal

• hepatic artery and portal vein bring blood to the hepatic sinusoids
• the blood flows from the sinusoids to the hepatic vein and then on to the IVC
• Liver has an enormous capacity for blood

Hepatic Venous System

• Budd-Chiari syndrome

Ø  blockage of the hepatic veins

Ø  frequently is associated with massive destruction of hepatocytes 2^o to severe congestion

Ø  tumors, leukemia, and polycythemia

Hepatic Arterial System

• Polyarteritis nodosa

Ø  hepatic infarction can occur, but rarely does (remember 2 bloods supplies)

Sinusoids

• Normal

Ø  normally lined by non-connected endothelial cells

v  allows large particles (like chylomicrons) to assess the hepatocytes

Ø  Ito cells (fat storage cellsthat contain Vit A and produce collagen fibers) and Kupffer cells (tissue macs) also line the sinusoids

Ø  Space of Disse – separates the cells lining the sinusoids from the hepatocytes

• Erythrophagocytosis

Ø  done by Kupffer cells

Ø  seen in abnormal red blood cells (ex. Sickle cell)

• Granulomas

Ø  hyperplasia of Kupffer cells

• Chronic passive congestion

Ø  dilatation of the sinusoids and thinning of the liver plates

• Amyloid

Ø  can accumulate in the space of Disse

• Leukemia

Ø  leukemic cells can be found in sinusoids

Responses to Injury in the Liver

I.                 Inflammation

• the type of inflammatory inflitrate (acute or chronic) is related to the nature of the disease state

II.               Regeneration

• tremendous capacity to regenerate
• 75% resection and the liver still can regenerate

III.              Fibrosis

• amount of fibrosis increases with sustained or recurrent injury
• can eventually result in cirrhosis

Tags: acinus, Amyloid, antitrypsin deficiency, Balooning Necrosis, canaliculi, Cholangitis, Classic lobules, Eosinophilic Necrosis, Erythrophagocytosis, falciform ligament, Fatty Metamorphosis, Glycogen Storage Diseases, granulomas, Hepatic Arterial System, Hepatic Venous, Kupffer cells, macrovesicular, Mallory's Hyaline, Microvesicular, sinusoids, vascular system

This entry was posted on Friday, June 19th, 2009 at 5:00 am and is filed under Pathophysiology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.