Hepatic system

Question 1

Describe the structure of the liver.

Answer 1

4 lobes: 2 major (left and right) - largest and 2 minor (caudate and quadrate)

Question 2

Describe the Glisson’s capsule.

Answer 2

• Well defined thin capsule of connective tissue
• Rich in nerve endings
• Covered by a single layer of mesothelium

Question 3

Where is the gallbladder?

Answer 3

Lodged within recess under right lobe

Question 4

State the function of the liver.

Answer 4

An exocrine gland - bile secretion

Question 5

What is a liver lobule?

Answer 5

Basic functional unit of liver

Question 6

What are hepatocytes?

Answer 6

Specialised epithelial cells

Question 7

Which two vessels does the liver receive blood from?

Answer 7

• Hepatic portal vein
• Hepatic artery

Question 8

Describe the hepatic portal vein.

Answer 8

• Not a true vein: conducts blood to liver and not directly to the heart
• Nutrient rich blood from digestive tract and spleen
• Filters toxins delivered from digestive tract
• 75% blood supply to liver

Question 9

Describe the hepatic artery.

Answer 9

• Oxygenated blood from aorta
• 25% blood supply

Question 10

What does the liver lobule have instead of capillaries?

Answer 10

Endothelium-lined spaced called sinusoids

Question 11

Which artery and vein discharge into the sinusoids?

Answer 11

• Hepatic artery
• Portal vein

Question 12

What are sinusoids partly lined with and what is their function?

Answer 12

• By phagocytes
• Destroy bacteria, worn out blood cells
• Hepatic stellate cells
• Pericytes found in space of Disse
• Retinoid storage (in lipid droplets)

Question 13

Approximately how much of the hepatocyte surface area faces sinusoid and what is the advantage of this?

Answer 13

~70%
- Maximises blood exchange

Question 14

State the functions of the liver.

Answer 14

• Xenobiotic detoxification and metabolism
• Decomposition of erythrocytes and excretion of bilirubin
• Bile Production
• Cholesterol synthesis and Lipogenesis
• Carbohydrate Metabolism
• Protein synthesis:
  Albumin (major osmolar component of blood serum)
  Coagulation
• Hormone production:
  Thrombopoietin (regulates platelet production by bone marrow)
• Angiotensin (raises blood pressure following renin activation)
• Storage of:
  Glycogen
  Vitamins A, D, E, K (fat soluble), B12 (water soluble)
  Iron, Copper

Question 15

Describe carbohydrate metabolism

Answer 15

• Liver receives glucose and other monosaccharides from the blood plasma
• Converted to glucose 6-phosphate and other intermediates of glycolysis
• Stored as glycogen (Glycogenesis), converted to FA or degraded

Question 16

When does the liver secrete glucose?

Answer 16

• When there is a major decline in blood glucose level
• Glucose derived from glycogen store (Glycogenolysis)
• Liver glycogen declines to zero in periods of starvation > 1day
• If glycogen exhausted – Gluconeogenesis

Question 17

What is the cori cycle?

Answer 17

Lactate (anaerobic glycolysis) transported to the liver,
converted into glucose

Question 18

What is the alanine cycle?

Answer 18

Degradation of proteins - amino groups transferred
to pyruvate, giving rise to alanine, transported to the liver and carbon skeleton converted into glucose

Question 19

Describe glucose regulation.

Answer 19

• After meals glucose mainly stored as glycogen in liver
• When more energy needed
  between meals, glycogen, fat & protein (last) are broken down & liver makes glucose.
• Hormones (insulin, glucagon, adrenalin, cortisol) signal change from storage to synthesis.

Question 20

Describe lipid metabolism.

Answer 20

• Liver converts glucose via acetyl-CoA into fatty acids
• Retrieves fatty acids from lipids supplied with chylomicrons from intestine
• Converted into neutral fats and phospholipids, soluble forms
• VLDL are formed (transport of fatty acids to other tissues)

Question 21

What is cholesterol used for?

Answer 21

• The synthesis of bile acids, cell membranes, hormones

Question 22

What happens to excess cholesterol?

Answer 22

Converted into bile acids or excreted with the bile.

Question 23

What are bile acids?

Answer 23

Steroids synthesised in the liver from cholesterol
- Amphipathic (have a polar and an apolar side); act as detergents
- Linked to amino acid to from BILE SALTS

Question 24

What does bile contain?

Answer 24

organic and inorganic (bile salts) components

Question 25

Describe the production of bile.

Answer 25

* Produced by hepatocytes and passes into bile canaliculi * Bile canaliculi carry bile back to the portal triad (opposite direction to blood)

Question 26

Describe the role of bile in lipid digestion.

Answer 26

Bile facilitate solubilisation of dietary lipids during digestion by micelle formation (promoting intestinal absorption of lipids)

Question 27

Describe bilirubin metabolism in the liver?

Answer 27

* Uptake of Bilirubin by hepatocytes: * Bilirubin dissociates from albumin & enters hepatocytes * Bilirubin conjugated with two glucuronic acids by UDP- glucuronyl transferase (bilirubin diglucuronide) * Conjugated bilirubin transported into bile canalculi and bile. * Process energy dependent and impaired in liver diseases * Intestinal bacteria degrade bilirubin to urobilinogen * 80% oxidised to stercobilin and excreted in faeces * 20% enters extrahepatic circulation and excreted in urine

Question 28

What does the liver act as?

Answer 28

* Liver acts as gatekeeper between circulation and absorbed substances * Liver principal site of metabolism

Question 29

What is the first pass effect?

Answer 29

Substance absorbed from GI tract passes through liver

Question 30

Describe the phase 1 reaction of drug metabolism.

Answer 30

* Convert parent compound into a more polar (hydrophilic) metabolite by adding or unmasking functional groups (-OH, -SH, -NH2, -COOH, etc.) * Often metabolites are inactive; may be sufficiently polar to be excreted

Question 31

Describe phase 2 reactions of drug metabolism.

Answer 31

* Conjugation with endogenous substrate to increase aqueous solubility * Conjugation with glucoronide, sulfate, acetate, amino acid etc.

Question 32

Describe transaminase enzymes - liver function assessments?

Answer 32

* Alanine aminotransferase (ALT) - Increased when cells of the liver are inflamed or undergo cell death - Rises dramatically in acute liver damage, such as viral hepatitis * Aspartate aminotransferase (AST) - Raised in acute liver damage; less specific for liver disease

Question 33

Describe cholestatic enzymes - liver function assessments.

Answer 33

* Alkaline Phosphatase (ALP): Raised in biliary tract damage and inflammation * Gamma-Glutamyl Transferase (GGT): Produced by the bile duct (sensitive marker for cholestatic damage) Raised in alcohol toxicity

Question 34

Describe a foetal and newborn liver?

Answer 34

* First trimester, liver main site of RBC production. By 32 weeks BM has taken over task * Low bilirubin glucuronyl transferase at birth (adult levels by 4 weeks) * Paediatric Jaundice

Question 35

Describe the liver in childhood.

Answer 35

* Liver produces insulin-like growth factor-1 (IGF-1), hormone plays role in childhood growth

Question 36

Describe the liver in old people.

Answer 36

* Oxidative capacity of liver decreases with age * Reduced metabolism: longer drug exposures and reduced toxin clearance

Question 37

What are the mechanisms of drug induced liver injury?

Answer 37

* Direct hepatocyte damage * Mitochondrial toxicity * Metabolite activity * Cholestasis