The liver Flashcards
Describe the liver in terms of its size and blood supply
- Largest visceral organ (1.5kg), approx 2-3% total body mass, O2 consumption approx 25-30%
- First major organ in line from gut
- Dual blood supply - portal vein (75%), hepatic artery (25%)
- Hepatic vein empties into inferior vena cava
- Bile ducts empty directly into gut
Describe the process of carbohydrate metabolism and the liver’s importance to this
4 types of carbohydrate metabolism:
- Glycogenesis
- Glycogenolysis
- Gluconeogenesis
- Glycolysis
Liver can store glycogen, convert galactose and fructose to glucose
Glucose transported across wall of small intestine and into circulatory system, transports it to liver
Hepatocytes pass glucose on through circulatory system, or store excess glucose as glycogen
Cells in body take up glucose in response to insulin
Describe glycogenesis
- Excess glucose entering the body is rapidly removed and stored as glycogen
- This is stimulated by insulin
- The liver stores large amounts of glycogen (80g)
Describe glycogenolysis
- When blood glucose decreases, liver activates other pathways to depolymerise (break down) glycogen back into glucose, return glucose back to blood
- Stimulated by glycogen + adrenaline
Describe gluconeogenesis
- When hepatic glycogen reserves become exhausted, blood glucose concentration still must be maintained
- Glucose instead synthesised from lactate, amino acids and glycerol (from triglycerides)
Describe glycolysis
- Process by which glucose is converted to pyruvate releasing energy to form ATP + NADH
Describe the process of lipid metabolism and the liver’s importance to this
The liver takes up fatty acids that can come from 3 sources:
- Dietary sources of triglycerides
- Stored in apidocytes
- Synthesised in liver
The liver supports the high rate of fatty acid oxidation for energy production, synthesises most lipoproteins required by the body, converts excess carbs + proteins into fatty acids to store in adipose cells, and preserves cholesterol homeostasis by synthesising and converting it to bile acids if in excess
Triglycerides are oxidised in hepatocytes to produce energy
Lipoproteins are synthesised in the liver
Excess carbohydrates and proteins are converted to fatty acids and triglycerides to store in adipose
Synthesis of large quantities of cholesterol and phospholipids - some are packed as lipoproteins 80% of cholesterol is converted into bile salts
Lipoproteins are used by cells to form membranes, intracellular structures, steroid hormones etc.
Describe the degradation of fatty acids and beta-oxidation
This process is lipolysis
- Triglycerides hydrolysed into glycerol and fatty acids. This process is stimulated by norepinephrine, epinephrine, glucocorticoids, thyroid hormone and growth hormone
- Glycerol can be converted further into PGAL, where it will enter the respiratory pathway until it forms G-6-P to form glucose, which can then be used to harvest energy
- Fatty acids are converted into Fatty acyl CoA by reacting with CoA, and then enter the respiratory pathway. This is beta oxidation.
Describe the process of protein metabolism and the liver’s importance to this
The liver regulates blood levels of amino acids:
Non-nitrogenous part converted to glucose + lipids
- Deamination and transamination of amino acids (forms nitrogen pool for urea cycle) followed by conversion of non-nitrogenous part to glucose + lipids. Enzymes alanine and aspartate aminotransferases are used in this process, and levels of these enzymes can be used to assess liver damage
This leads to synthesis of 80% plasma proteins:
- Albumin (major plasma protein) - if not enough albumin produced, it will lead to oedema as interstitial fluid will not return back into the capillaries
- Complement cascade proteins (involved in immune function)
- Transferin
- Coagulation factors
Ammonia is a by-product of protein metabolism and must be excreted in urine as urea
Synthesis of urea removes ammonia from the body:
- Ammonia = toxic because depresses cerebral blood flow and oxygen consumption and interferes with GABA and dopamine = hepatic encephalopathy
- Large amounts of ammonia formed by gut bacteria and ammonia
- No urea formation = increased plasma ammonia
What are the cells of the liver and what are their functions?
- Hepatocytes (60%) - perform most metabolic functions
- Kupffer cells (30% of NPC) - type of tissue macrophage
- Liver and sinusoidal endothelial cells (LSEC)
- Stellate cells
Describe the hepatic lobule
- Hexagonal plates of hepatocytes around central hepatic vein
- At each of 6 corners is triad of branches of portal vein, hepatic artery and bile duct
How are kupffer cells involved in the protective function of the liver?
- Represent approx 80% of all fixed tissue macrophages
- Function as mononuclear phagocyte system - engulf and destroy bacteria, viruses etc, and ingest worn-out or abnormal body cells
- These and hepatocytes lining the sinusoids have pathogen recognition receptors (PRR) to recognise PAMP (pathogen associated molecular patterns) enabling them to detect pathogens
How are LSECs (liver sinusoidal endothelial cells) involved in the protective function of the liver?
- Form an intact sinusoidal wall that separates blood flow from the hepatocytes
- Important physiological + immunological functions including filtration, endocytosis, antigen presentation, and immunoregulatory effect
- Mediate immune tolerance in response to pathogenic factors such as PAMPs, to prevent inflammatory injuries
- Capable of eliminating blood-borne microorganisms and molecules, including viruses
What is bile?
- Complex fluid consisting of water, electrolytes + mix of organic molecules (bile acids, cholesterol, bilirubin, phospholipids)
How does the liver produce bile?
- Liver synthesises bile acids from cholesterol to primary bile acids (Cholic acids - has 3 OH groups-, Chenodeoxycholic acid- has 2 OH groups)
- Synthesis is regulated by the enzyme 7 α- hydroxylase with requires O2, NADH and cytochrome (P-450)
- Presence of -COOH and -OH groups makes bile acids more water soluble than cholesterol
- Primary acids conjugate with glycine or taurine, prior to secretion into bile canalicular (ratio of glycine to taurine 3:1)
- Conjugated bile salts in sinusoidal blood actively taken up and transported against concentration gradient into bile canaliculi
