Jan 29 - Liver Disease: Hepatitis Flashcards
What is the difference between the blood supply to the liver and the other organs?
The liver has two sources where it receives blood: the hepatic artery and the hepatic portal vein. The hepatic artery delivers oxygenated blood from the general circulation. The hepatic portal vein delivers deoxygenated blood from the small intestine containing nutrients (75% of blood flowing through the liver arrives via the hepatic portal vein)
Describe the blood flow through the liver
Blood flows through the liver tissue to the hepatic cells where many metabolic functions take place. The blood drains out of the liver via the hepatic vein. The liver tissue is not vascularized with a capillary network as most other organs; however it consists of blood filled sinusoids surrounding the hepatic cells
What does the liver manufacture?
Albumin, bile, urea and blood proteins
What is albumin?
A protein that regulates the fluid balance in our body’s blood clotting factors
What is bile?
It is used for digestion
How is urea produced?
Deamination of amino acids and conversion of ammonia to urea via the urea cycle
What is the role of blood proteins?
They aid in clotting, oxygen transport and immune system function
What does the liver transform?
Bilirubin, cholesterol, carbohydrates, saturated fats
What is bilirubin?
A pigment released when red blood cells die and becomes a water-soluble substance excreted in the bile
What does the liver do with cholesterol and fatty acids??
It synthesizes cholesterol from acetate, it synthesizes triglycerides from fatty acids. It secretes both in VLDL particles. It takes up cholesterol and triglycerides via endocytosis of HDL and LDL particles, then it excretes cholesterol in bile, beta-oxidizes fatty acids and converts excess acetyl-CoA into ketones
What does the liver do to carbohydrates?
The liver converts sugars into glucose (via gluconeogenesis and glycogenolysis)
It also used glucose for glycogen synthesis, fatty acid synthesis, glycolysis and the tricarboxylic acid cycle
What does liver clean and detoxify?
Bacteria, ammonia, alcohol, both prescription and over the counter drugs, other toxins
What does the liver store?
Glycogen, for energy
Iron
Other vitamins
What are the five functions of the liver?
Energy metabolism and substate interconversion Protein synthesis (clotting factors) Solubilization, transport and storage Detoxification and clearance Bile production
Why does hypoglycemia occur?
Hypoglycemia occurs primarily due to a decrease in “functional hepatocyte mass” (ability to produce and release stored glucose is impaired)
Why does hyperglycemia occur?
Hyperglycemia can occur due to portal-systemic shunt
What are clinical consequences of liver disease?
Hepatocyte dysfunction - manifests as failure of one or more of the main liver functions
Portal hypertension - cirrhosis is often a primary cause, but can also be caused by portal-systemic shunt
What are tests of liver injury?
Aspartate aminotransferase (AST) - indicates hepatocyte death Alanine aminotransferase (ALT) - indicates liver injury Alkaline phosphatase (ALP) - this is also found in the bone, intestine and placenta, which is why GGT is required Gamma glutamyl transpeptidase (GGT) + ALT = liver or biliary tract disease
What are tests of liver function?
Bilirubin -direct bilirubin (conjugated) -total bilirubin (unconjugated) Albumin Prothrombin time (international normal ratio - INR)
What is the leading cause of liver transplants?
Hepatitis C virus
How is Hepatitis A virus spread?
Oral fecal transmission
How is Hepatitis B virus spread?
Spread through blood or body fluids
What is hepatocellular disease?
Injury to hepatocytes, leading to decrease synthetic/metabolic functions (AST/ALT)
What is cholestatsis?
Impaired bile formation (hepatocytes)
Impaired bile flow (bile ducts)
What is liver disease? What are the causes? What are the consequences?
Non-alcoholic fatty liver disease (NAFLD)
NAFLD + inflammation + fibrosis = Non-alcoholic steatohepatitis (NASH)
Some individuals eventually leads to fibrosis and subsequent cirrhosis
75% of obese individuals are at risk of developing simple fatty liver
First stage in alcoholic liver disease
What are the causes of hepatitis?
Immune cells in the body attacking the liver and causing autoimmune hepatitis
Infections from viruses (Hep A, B or C), bacteria or parasites
Liver damage from alcohol, poisonous mushrooms or other poisons
Medications, such as an overdose of acetaminophen which can be deadly
What is hepatitis?
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ
What is the most common symptom of hepatitis?
Hepatitis may occur with limited or no symptoms, but often leads to yellow discoloration of the skin, mucus membranes and conjunctivae (whites of the eyes), poor appetite and malaise (tiredness)
What is the difference between acute and chronic hepatitis? How does the condition progress?
Hepatitis is acute when it lasts less than six months and chronic when it persists longer. The condition can be self-limiting (healing on its own) or can progress to fibrosis (scarring) and cirrhosis
What are the types of of hepatitis?
Viral hepatitis Alcoholic hepatitis Toxic and drug-induced hepatitis Autoimmune Non-alcoholic fatty liver disease (NAFLD) Ischemic hepatitis Giant cell hepatitis
Describe viral hepatitis
The most common cause of viral hepatitis are five unrelated hepatotropic viruses hepatitis A, hepatitis B, hepatitis C, hepatitis D (which requires hep B to cause disease) and hepatitis E
Describe alcoholic hepatitis
Excessive alcohol consumption is a significant cause of hepatitis and liver damage (cirrhosis). Alcoholic hepatitis usually develops over years-long exposure to alcohol
Describe toxic and drug-induced hepatitis
A large number of medications and other chemical agents can cause hepatitis. In the United States, acetaminophen, antibiotics and central nervous system medications are among the most common causes of drug-induced hepatitis
Describe autoimmune hepatitis
A chronic disease caused by an abnormal immune response against liver cells
Describe NAFLD
The occurrence of fatty liver in people who have little or no history of alcohol use. In the early stage there are usually no symptoms, as the disease progresses symptoms typical of chronic hepatitis may develop. NAFLD is associated with metabolic syndrome, obesity, diabetes and hyperlipidemia. Severe NAFLD leads to inflammation, fibrosis and cirrhosis, a state referred to as non-alcoholic steatohepatitis (NASH)
What are symptoms of hepatits
Abdominal pain or distension, breast development in males, dark urine and pale or clay-coloured stools, fatigue, fever (usually low grade), general itching, jaundice (yellowing of the skin or eyes), loss of appetite, nausea and vomiting, weight loss
Describe HAV
Small RNA virus, spread via fecal-oral transmission
Recovery results in immunity
Describe HBV
Mostly asymptomatic or mild symptoms
Body fluid and sexual transmission
Hepatocyte death via immune response to infection
Describe HCV
Body fluid and sexual transmission
Mostly asymptomatic or mild symptoms
Describe the pathogenesis of acute hepatitis
Hepatocyte infection Viral replication Viral components illicit immune response (inflammation, hepatocyte death) Changes in LFT's appear Manifestations of liver disease
Describe the prodrome of acute hepatitis
Early sypmtoms Last 3-4 days Nonspecific signs and symptoms GI symptoms Extrahepatic symptoms
Describe the icteric phase
Actual phase of illness
Last 1-4 weeks
Describe the convalescent phase
Gradual recovery phase
Constitutional signs and symptoms resolve
Describe acute toxic hepatitis
Most cases of drug-induced liver disease present as acute hepatitis, some as cholestasis.
Toxicity may be predictable and dose related or unpredictable and not dose related (idiosyncratic)
Acetaminophen overdose is the leading cause of fulminant hepatitis in the US and the UK
Some drug regimens may warrant monitoring of LFTs (thiazolidinedions, statins)
Describe acute alcoholic hepatitis
Ethanol has direct and indirect hepatotoxic effects
Ethanol increases the fluidity of cellular membranes
Byproducts of its metabolism (NADH) inhibit gluconeogenesis and fatty acid oxidation
Fatty acid synthesis is promoted
Toxicity is unpredictable and the “dose” required to produce acute toxicity is variable
