Jan 29 - Liver Disease: Hepatitis

Question 1

What is the difference between the blood supply to the liver and the other organs?

Answer 1

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)

Question 2

Describe the blood flow through the liver

Answer 2

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

Question 3

What does the liver manufacture?

Answer 3

Albumin, bile, urea and blood proteins

Question 4

What is albumin?

Answer 4

A protein that regulates the fluid balance in our body’s blood clotting factors

Question 5

What is bile?

Answer 5

It is used for digestion

Question 6

How is urea produced?

Answer 6

Deamination of amino acids and conversion of ammonia to urea via the urea cycle

Question 7

What is the role of blood proteins?

Answer 7

They aid in clotting, oxygen transport and immune system function

Question 8

What does the liver transform?

Answer 8

Bilirubin, cholesterol, carbohydrates, saturated fats

Question 9

What is bilirubin?

Answer 9

A pigment released when red blood cells die and becomes a water-soluble substance excreted in the bile

Question 10

What does the liver do with cholesterol and fatty acids??

Answer 10

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

Question 11

What does the liver do to carbohydrates?

Answer 11

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

Question 12

What does liver clean and detoxify?

Answer 12

Bacteria, ammonia, alcohol, both prescription and over the counter drugs, other toxins

Question 13

What does the liver store?

Answer 13

Glycogen, for energy
Iron
Other vitamins

Question 14

What are the five functions of the liver?

Answer 14

Energy metabolism and substate interconversion
Protein synthesis (clotting factors)
Solubilization, transport and storage
Detoxification and clearance
Bile production

Question 15

Why does hypoglycemia occur?

Answer 15

Hypoglycemia occurs primarily due to a decrease in “functional hepatocyte mass” (ability to produce and release stored glucose is impaired)

Question 16

Why does hyperglycemia occur?

Answer 16

Hyperglycemia can occur due to portal-systemic shunt

Question 17

What are clinical consequences of liver disease?

Answer 17

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

Question 18

What are tests of liver injury?

Answer 18

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

Question 19

What are tests of liver function?

Answer 19

Bilirubin
-direct bilirubin (conjugated)
-total bilirubin (unconjugated)
Albumin
Prothrombin time (international normal ratio - INR)

Question 20

What is the leading cause of liver transplants?

Answer 20

Hepatitis C virus

Question 21

How is Hepatitis A virus spread?

Answer 21

Oral fecal transmission

Question 22

How is Hepatitis B virus spread?

Answer 22

Spread through blood or body fluids

Question 23

What is hepatocellular disease?

Answer 23

Injury to hepatocytes, leading to decrease synthetic/metabolic functions (AST/ALT)

Question 24

What is cholestatsis?

Answer 24

Impaired bile formation (hepatocytes)

Impaired bile flow (bile ducts)

Question 25

What is liver disease? What are the causes? What are the consequences?

Answer 25

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

Question 26

What are the causes of hepatitis?

Answer 26

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

Question 27

What is hepatitis?

Answer 27

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

Question 28

What is the most common symptom of hepatitis?

Answer 28

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)

Question 29

What is the difference between acute and chronic hepatitis? How does the condition progress?

Answer 29

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

Question 30

What are the types of of hepatitis?

Answer 30

``` Viral hepatitis Alcoholic hepatitis Toxic and drug-induced hepatitis Autoimmune Non-alcoholic fatty liver disease (NAFLD) Ischemic hepatitis Giant cell hepatitis ```

Question 31

Describe viral hepatitis

Answer 31

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

Question 32

Describe alcoholic hepatitis

Answer 32

Excessive alcohol consumption is a significant cause of hepatitis and liver damage (cirrhosis). Alcoholic hepatitis usually develops over years-long exposure to alcohol

Question 33

Describe toxic and drug-induced hepatitis

Answer 33

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

Question 34

Describe autoimmune hepatitis

Answer 34

A chronic disease caused by an abnormal immune response against liver cells

Question 35

Describe NAFLD

Answer 35

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)

Question 36

What are symptoms of hepatits

Answer 36

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

Question 37

Describe HAV

Answer 37

Small RNA virus, spread via fecal-oral transmission | Recovery results in immunity

Question 38

Describe HBV

Answer 38

Mostly asymptomatic or mild symptoms Body fluid and sexual transmission Hepatocyte death via immune response to infection

Question 39

Describe HCV

Answer 39

Body fluid and sexual transmission | Mostly asymptomatic or mild symptoms

Question 40

Describe the pathogenesis of acute hepatitis

Answer 40

``` Hepatocyte infection Viral replication Viral components illicit immune response (inflammation, hepatocyte death) Changes in LFT's appear Manifestations of liver disease ```

Question 41

Describe the prodrome of acute hepatitis

Answer 41

``` Early sypmtoms Last 3-4 days Nonspecific signs and symptoms GI symptoms Extrahepatic symptoms ```

Question 42

Describe the icteric phase

Answer 42

Actual phase of illness | Last 1-4 weeks

Question 43

Describe the convalescent phase

Answer 43

Gradual recovery phase | Constitutional signs and symptoms resolve

Question 44

Describe acute toxic hepatitis

Answer 44

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)

Question 45

Describe acute alcoholic hepatitis

Answer 45

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