What are the two blood supplies of the liver?
The portal vein (60-70%); and the hepatic artery (30-40%).
What is the role of the hepatic artery and the portal vein?
The hepatic artery supplies oxygen rich blood; the portal vein carries nutrient rich blood from the digestive tract.
Describe organization within the liver:
Within the lobule, hepatocytes are organized into plates, which radiate out from a central vein; sinusoids form the space between hepatic plates.
Describes the production and release of bile:
It is produced by hepatocytes; and drains into the bile duct.
What are the primary disorders of the liver?
Viral hepatitis; non-alcoholic fatty liver; alcoholic liver disease; hepatocellular carcinoma.
What is the typical nature of liver disease?
Typically insidious; detection is often delayed.
What are some examples of reversible hepatocyte damage?
Accumulation of fat (steatosis); accumulation of bilirubin (cholestasis).
What happens if hepatocyte damage is irreversible?
Necrosis; apoptosis. Regeneration may also occur.
What 3 laboratory tests are used to assess hepatocyte integrity?
Serum Aspartate Aminotransferase (AST)
Serum Alanine Aminotransferase (ALT)
Serum Lactate Dehydrogenase (LDH)
What 3 laboratory tests are used to assess biliary excretory function?
Total Bilirubin
Direct Bilirubin (conjugated)
Urine Bilirubin
What laboratory tests are used to evaluate hepatocyte synthetic function?
PT
PTT
Serum Ammonia
Which liver cell is responsible for hepatic scar deposition?
Hepatic stellate cell; has a quiescent form (vitamin A storage molecule) and an active form (fibrogenic myofibroblast).
How are hepatic stellate cells activated?
Kupffer cells and lymphocytes release cytokine and chemokines that shift gene expression toward fibrogenesis.
What stimuli can activate hepatic stellate cells?
Chronic inflammation; disruption of the ECM, toxins.
Describe the role of inflammation and immunity in liver disease?
Inflammation can cause vascular disturbance, scarring, and malignant transformation; Adaptive immunity plays a crucial role in eradication of hepatitis.
What is the most severe consequence of liver disease?
Liver failure; can be caused by sudden destruction, acute failure, or chronic failure; typically results from decades of progressive injury.
How much liver function must be lost in order for liver failure to occur?
80-90%; transplant is the best hope for survival.
What is the cause of acute liver failure?
Usually caused by drugs or toxins (APAP) resulting in massive necrosis; occurs within 26 weeks of initial injury. Usually involves immune-mediated destruction.
What are the symptoms of acute liver failure?
Nausea; vomitting; jaundice; progresses to life threatening encephalopathy and coagulation; liver initially swells due to edema, but later shrinks; multi-organ failure ensues.
What are some other manifestations of acute liver failure?
Portal hypertension due to vascular obstruction leads to ascites and encephalopathy; hepatorenal failure can occur.
What are the major causes of chronic liver failure?
Hepatitis B and C; non-alcoholic fatty liver; and alcoholic liver disease -- commonly associated with cirrhosis.
What are the symptoms of chronic liver disease?
Many are asymptomatic until advanced stage; symptoms are non-specific (anorexia, weight-loss, weakness); may lead to the development of carcinoma.
What is the ultimate cause of death in those with chronic liver failure?
The same as acute liver failure; ascites, encephalopathy; organ failure.
What are the three general causes of portal hypertension (ascites)?
Pre-hepatic obstruction (massive splenomegaly); intra-hepatic obstruction (cirrhosis -- most common); post-hepatic obstruction (RVHF; pericarditis).
What are the four consequences portal hypertension?
Ascites; venous shunt formation; congestive splenomegaly; hepatic encephalopathy.
What is ascites?
Accumulation of excess fluid in the peritoneal cavity; fluid is mostly serous; detectable at 500 ml.
What are the three pathogenic mechanisms behind ascites?
Portal hypertension; lymph accumulation; vasodilation.
What is hepatitis?
Describes a collection of viruses that have an affinity for the liver, and a pattern of hepatic injury that occurs in infected individuals. Any form of infectious liver disease may also be called hepatitis (EBV, mononucleosus, etc.)
What are some characteristics of hepatitis A?
It is usually a benign, self-limited disease that does not cause chronic hepatitis; acute liver failure is low, fatality is rare; it is often asymptomatic and rare after childhood.
How is hepatitis A transmitted?
Usually spreads through contaminated food or water; may also be detected in saliva; sporadic infections are associated with the consumption of raw shellfish; the incubation period is 2-6 weeks.
Why is hepatitis B infection a major health concern?
1/3 of the world is infected; the incubation period is long (4-26 weeks), and it can be transmitted through blood.
How is hepatitis B usually transmitted?
Occurs during childbirth in 90% of cases; can also be acquired through unprotected sex and intravenous drug use.
What are the five possible outcomes of hepatitis B infection?
Acute hepatitis with recovery; non-progressive chronic hepatitis; progressive chronic disease and cirrhosis; acute liver failure and massive necrosis; and induction of an asymptomatic carrier state.
How is age at the time of HBV infection associated with probability of chronicity?
The younger the age at the time of infection, the higher the probability of chronic disease.
How can HBV be prevented?
Vaccination.
What are the four serological tests of HBV-specific antigens and antibodies?
HBsAg: presence indicates infection.
Anti-HBs: indicates recovery, immunity, vaccination.
Anti-HBc: indicates previous or ongoing infection.
IgM Anti-HBc: indicates recent acute infection.
What is the major cause of liver disease worldwide?
Hepatitis C.
What are the characteristics of hepatitis C infection?
Acute infection is typically asymptomatic; the hallmark is persistent infection and chronic hepatitis; cirrhosis occurs in 20%; the incubation period averages 9 weeks.
What are the four clinical syndromes that can occur following hepatitis infection?
Acute asymptomatic infection with recovery; acute symptomatic infection with recovery; chronic infection with or without progression to cirrhosis; acute liver failure with necrosis.
What is the carrier state of hepatitis?
Harboring with the ability to transmit, but without manifestation of symptoms.
What is the association between HIV and viral hepatitis?
Co-infection has become common; hepatitis B and C are the leading cause of morbidity is those with HIV; liver disease is the second most common cause of death in those with AIDS.
What is drug and toxin induced liver injury?
Damage from therapeutic and environmental agents; injury can result from direct toxicity, hepatic conversion, or immune mechanisms.
What agent produces more liver injury than any other agent?
Alcohol.
What are the three forms of alcoholic liver injury?
Hepatic steatosis (fatty change); alcoholic hepatitis; and steatofibrosis. Cirrhosis only develops in a small number of alcoholics.
How much alcohol must be consumed in order to significantly increase the risk for hepatic injury?
80 grams or more per day.
What are some other features of alcoholic liver injury?
Women are more susceptible; metabolism of alcohol generates ROS; alcohol can cause the release of bacterial endotoxin.
What are the clinical features of alcoholic liver disease?
Steatosis; hepatomegaly; elevated serum AST; cirrhosis.