MB2080: Topic 5 - Liver Physiology

Main functions of the liver

• metabolism

• protein synthesis

• protection & clearance of toxins

• solubilise, transport & storage

Liver blood supply

• hepatic artery — oxygenated blood from the heart to liver

• hepatic portal vein — deoxygenated, nutrient & toxin-rich blood from gut spleen & pancreas to liver (for detoxification)

• hepatic central vein — deoxygenated blood from liver to heart

Liver blood supply %

• 30% — hepatic artery

• 70% — hepatic portal vein

Liver lobule

hexagonal functional unit of the liver

Liver lobule structure

• central (hepatic vein) in the middle

• portal triad at each corner of the lobule

Sinusoids

blood vessels within the liver that run between hepatocytes

Bile canaliculi

channels between adjacent hepatocytes that collect bile and transport it toward larger bile ducts

Label this diagram

1. microvilli

2. nucleus

3. RER

4. tight junction

5. SER

6. space of Disse

7. fenestrations

8. Golgi body

9. apical membrane

10. bile canaliculus

11. basolateral membrane

12. hepatic stellate cells

13. endothelium (of sinusoid)

Components of a portal triad

• hepatic artery

• hepatic portal vein

• bile duct

Features of zone 1

• peri-portal region

• maximal oxygenation & nutrients

• most resistant to circulatory compromise

• 1st to regenerate

Zone 1 reactions

• amino acid catabolism

• gluconeogenesis

• glycogen degradation

• ureagenesis

• oxidative energy metabolism

Features of zone 3

• peri-central region

• minimal oxygenation

• maximal toxins & metabolites

• least resistant to circulatory compromise

Zone 3 reactions

• lipogenesis

• glycolysis

• glycogenesis

• bile acid biosynthesis

• biotransformation of gas

Zone 2

mid lobular region

Effect of insulin on the liver

• β-cells secrete insulin into blood stream (when blood glucose levels are high)

• insulin binds to IRS-1 on the hepatocyte membrane

• increased GLUT2 translocation to hepatocyte membrane leading to increased glucose uptake from the bloodstream

• activation of glycogen synthase

• activation of hexokinase

• activation of acetyl CoA carboxylase to store excess glucose as triglycerides

Glycogen synthase

converts glucose into glycogen

Hexokinase

converts glucose to pyruvate

Acetyl CoA carboxylase

converts pyruvate to fatty acids to store excess glucose as triglycerides

Effect of glucagon on the liver

• α-cells secrete glucagon into blood stream (when blood glucose levels are low)

• reduced GLUT2 translocation to hepatocyte membrane leading to reduced glucose uptake from the bloodstream

• activation of glycogen phosphorylase

• activation of glucagon-6-phosphatase

• releases glucose into the bloodstream

Glycogen phosphorylase

breaks down glycogen by catalysing the phosphorolysis of -1,4-glycosidic bonds

Glucose-6-phosphatase

converts glucose 6-phosphate to glucose releasing glucose into the bloodstream

Specific non-essential amino acids

• alanine

• glycine

• proline

• tyrosine

• aspartic acid

• glutamic acid

• arginine

• serine

• cysteine

• asparagine

• glutamine

Non-essential amino acids

amino acids naturally synthesized by the body

Specific essential amino acids

• histidine

• isoleucine

• leucine

• lysine

• methionine

• phenyl-alanine

• threonine

• tryptophan

• valine

Essential amino acids

amino acids not synthesized by the body which need to be absorbed from diet

Protein synthesis by hepatocytes

• triggered by certain hormones (such as insulin)

• influenced by the availability of amino acids

• occurs in balance with protein degradation and intake

Proteins synthesized by the liver (and examples)

• plasma proteins e.g. albumin

• coagulation factors e.g. fibrinogen

• pro-hormones e.g. angiotensinogen

• lipoproteins e.g. low-density lipoprotein (LDL)

Function of lipoproteins

enable transport of insoluble lipids and cholesterol throughout the body

Examples of lipoproteins

• chylomicrons (high content of triglycerides & cholesterol but minimal protein)

• LDL (low density lipoprotein, high content of fats compared to protein)

• HDL (high density lipoprotein, high content of protein compared to fats)

Protein catabolism

deamination of amino acids into α-keto acids and ammonia

Urea cycle

process of converting toxic ammonia into non-toxic urea for excretion from the body via the urine