Liver Function & Failure

Question 1

What is the dual blood supply of the liver?

Answer 1

Hepatic artery and hepatic vein.

Question 2

What are liver lobules made up of?

Answer 2

Hepatocytes, bile ducts and blood vessels = functional units called liver lobules.

Question 3

What are sinusoids and why are they important to the liver?

Answer 3

Highly permeable capillaries.

This allows components of the blood to move easily into hepatocytes for processing (e.g. hormones, drugs, toxins, bilirubin) and substances produced by hepatocytes can more easily be transported into the blood (e.g. plasma proteins).

Question 4

What are Kupffer cells and what are their function?

Answer 4

Macrophages located in the sinusoids.
Functions:
1. Destruction of old, damaged RBCs and platelets and cell debris.
2. Remove microorganisms.
3. Storage of iron.

Question 5

Describe bilirubin metabolism.

Answer 5

• Unconjugated bilirubin (lipid-soluble) is derived from the breakdown of heme (mainly in the spleen)
• carried to the liver bound to albumin
• Unconjugated bilirubin is converted by glucuronic acid into conjugated bilirubin (water-soluble) in hepatocytes
• conjugated bilirubin is excreted in the bile
• bacteria in the colon convert bilirubin into urobilinogen (water-soluble) of which some is absorbed from the colon and filtered by the kidneys
• urobilinogen that is not absorbed is further digested by bacteria to stercobilin which gives feces its brown colour

Question 6

What is juandice (icterus)?

Answer 6

The yellow discolouration of skin and sclera.

• caused by accumulation of bilirubin in the blood = hyperbilirubinemia
• binds to connective tissue and stains it yellow

Question 7

What is prehapatic juandice (hemolytic)?

Answer 7

Occurs secondary to an excessive destruction of RBCs (e.g. hemolytic anemia, transfusion reactions)
- liver function normal but cannot handle the additional bilirubin
- causes unconjugated hyperbilirubinemia = causes jaundice, detected in urine by dipstick, stool colour normal

Question 8

What is posthepatic jaundice (obstructive)?

Answer 8

Caused by the obstruction of bile flow from the liver to the duodenum
e.g. gallstones or a pancreatic tumour
- bilirubin is conjugated, but not excreted
- conjugated bilirubin and bile salts back up into the blood = conjugated hyerperbilirubinemia

Causes:
- jaundice
- dark brown and foamy urine = conjugated bilirubin is filtered by the kidneys and present in urine
- light or clay-coloured stools = obstructed bile flow into intestines means that less bilirubin is being converted to stercobilin in the colon
- steatorrhea = impaired digestion of fats d/t impaired bile release
- pruritus = itching caused by accumulation of bile slats in the blood and deposit in the skin

Question 9

What is intrahepatic jaundice (hepatocellular)?

Answer 9

• failure of hepatocytes to take up conjugate or excrete bilirubin

Occurs with liver diseases (e.g. hepatitis) causing both:
- hepatocyte damage = loss of hepatocytes need to conjugate bilirubin
- bile canaliculi obstruction = compression d/t inflammation

Causes mixed hyperbilirubinemia

Question 10

What is neonatal jaundice?

Answer 10

Many neonates develop jaundice 2-3 days after birth d/t:
1. increase in breakdown of fetal RBCs
2. low levels of enzymes needed to conjugate bilirubin in the first two weeks following birth

Causes prehepatic and intrahepatic jaundice.

In severe cases, unconjugated bilirubin can enter the brain of infants and cause damage = kernicterus

Phototherapy decreases bilirubin levels within 24-48 hours

Question 11

What are the major plasma proteins synthesized by the liver?

Answer 11

Albumin = maintains blood colloid osmotic pressure

Clotting factors

Complement proteins = defence against bacterial infections

Transport proteins = e.g. for iron, vit B12, and lipid-soluble hormones

Question 12

What are the effects of albumin deficiency?

Answer 12

Low blood colloid osmotic pressure causes edema (generalized) d/t reduced pressure pulling fluids into the blood

Question 13

How is urea formed?

Answer 13

Hepatocytes convert ammonia (formed during amino acid catabolism) to urea

Urea is water-soluble, enters the blood and is excreted by the kidneys, saliva, and sweat.

Amino acid catabolism occurs in:
1. hepatocytes = used for glucose or ATP synthesis
2. in the intestines during protein digestion
3. in muscle cells for energy production

Question 14

Hepatocytes convert alcohol to?

Answer 14

Acetaldehyde

Question 15

What does hepatocyte metabolism of drugs include?

Answer 15

Inactivation of drugs (limits duration of action)

Converts lipophilic drugs to hydrophilic so they can be excreted in the urine or bile

Question 16

What happens to blood ammonia levels in impaired detoxification

Answer 16

Elevated blood levels
- ammonia is a neurotoxin
- causes hepatic encephalopathy
- manifests as changes in consciousness (disorientation, confusion, coma), intellectual capacity, nueromuscular funciton (tremour, asterixis, slurred speech) and personality

Question 17

What happens when metabolism of drugs is impaired?

Answer 17

• Drugs accumulate at potentially harmful levels
• requires adjusting drug dosages

Question 18

Which hormones are inactivated by hepatocytes?

Answer 18

• steroid hormones = converted to water-soluble form for kidney excretion
• thyroid hormone = is deiodinated
• insulin = undergoes proteolysis

Question 19

What happens with impaired inactivation of estrogen?

Answer 19

• gynecomastia (breast enlargement) and testicular atrophy in males
• menstrual irregularities
• spider angiomas (dilated arterioles beneath the skin surface)

Question 20

What happens with impaired aldosterone inactivation?

Answer 20

• elevated aldosterone levels = Na+ and water retention
• causes HTN and generalized edema

Question 21

What is involved in glucose metabolism?

Answer 21

The liver maintains blood glucose levels by:
- synthesizing glucose (glycogenolysis, gluconeogenesis)
- storing glucose (glycogenesis)

Question 22

How would liver failure affect blood glucose levels?

Answer 22

• reduced ability to take in and store glucose
• reduced gluconeogenesis or glycogen reserves
  = hypoglycemia (fatigue, weakness, hunger, light-headed, dizziness, irritability, increased HR, sweating)

Question 23

Describe lipid metabolism in the liver.

Answer 23

• converts fatty acids to cholesterol, ketones, or energy
• stores lipids as TGs when blood levels are high
• packages TGs and cholesterol into lipoproteins for transport to body cells

Question 24

What occurs in impaired fat metabolism?

Answer 24

Impaired formation of lipoproteins or TG breakdown = fatty liver (reversible)

Question 25

Describe bile synthesis in the liver.

Answer 25

• Bile synthesized in the liver - 1L/day
• consists mainly of water, bile salts, cholesterol, lecithin, bilirubin, bicarbonate and electrolytes
• released into the duodenum to assist fat digestion

Question 26

How does bile assist in fat digestion?

Answer 26

Bile salts emulsify fats (surround smaller fat droplets)

Increase surface area for pancreatic lipase which is not lipid soluble

Question 27

What will be the effect of impaired bile synthesis?

Answer 27

Impaired lipid digestion and absorption:
- fatty, foul-smelling stolls (steatorrhea)
- impaired absorption and deficiency of fat-soluble vitamins (A, D, E and K)

Question 28

What role does the liver play in Vit D activation?

Answer 28

• liver converts Vit D in the diet or synthesized in the skin to 25-hydroxy-D3
• this travels in the blood to the kidneys to be activated into calcitriol

Question 29

What role does the liver play in vitamin and mineral storage?

Answer 29

• iron, fat soluble vitamins (A, D, E and K) and vitamin B12 are stored in the liver when in excess
• reintroduced to the blood when levels are low

Question 30

What happens with impaired vit D activation or storage?

Answer 30

Impaired activation of Vit D can lead to a Vit D deficiency:
- Vit D is needed for the absorption of calcium from the intestines and immune funciton
- a deficiency can contribute to hypocalcemia, bone weakening, muscle weakness and recurrent infections

Question 31

What do aminotransferases (ALT and AST) indicate in a blood test?

Answer 31

• leak out of damaged hepatocytes
• elevated blood levels reflect liver damage

Question 32

What does alkaline phosphate in a blood test indicate?

Answer 32

• found in cells lining bile ducts within the liver
• elevated blood levels = suggests biliary disorders or abnormal bile flow

Question 33

What tests other then liver enzyme levels may be performed to assess liver function?

Answer 33

• blood albumin (decreased)
• blood bilirubin (elevated)
• ammonia (increased)
• fibrinogen levels (decreased)
• PT and PTT (prolonged)