Hepatic system Flashcards
Describe the structure of the liver.
4 lobes: 2 major (left and right) - largest and 2 minor (caudate and quadrate)
Describe the Glisson’s capsule.
- Well defined thin capsule of connective tissue
- Rich in nerve endings
- Covered by a single layer of mesothelium
Where is the gallbladder?
Lodged within recess under right lobe
State the function of the liver.
An exocrine gland - bile secretion
What is a liver lobule?
Basic functional unit of liver
What are hepatocytes?
Specialised epithelial cells
Which two vessels does the liver receive blood from?
- Hepatic portal vein
- Hepatic artery
Describe the hepatic portal vein.
- 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
Describe the hepatic artery.
- Oxygenated blood from aorta
- 25% blood supply
What does the liver lobule have instead of capillaries?
Endothelium-lined spaced called sinusoids
Which artery and vein discharge into the sinusoids?
- Hepatic artery
- Portal vein
What are sinusoids partly lined with and what is their function?
- By phagocytes
- Destroy bacteria, worn out blood cells
- Hepatic stellate cells
- Pericytes found in space of Disse
- Retinoid storage (in lipid droplets)
Approximately how much of the hepatocyte surface area faces sinusoid and what is the advantage of this?
~70%
- Maximises blood exchange
State the functions of the liver.
- 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
Describe carbohydrate metabolism
- 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
When does the liver secrete glucose?
- 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
What is the cori cycle?
Lactate (anaerobic glycolysis) transported to the liver,
converted into glucose
What is the alanine cycle?
Degradation of proteins - amino groups transferred
to pyruvate, giving rise to alanine, transported to the liver and carbon skeleton converted into glucose
Describe glucose regulation.
- 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.
Describe lipid metabolism.
- 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)
What is cholesterol used for?
- The synthesis of bile acids, cell membranes, hormones
What happens to excess cholesterol?
Converted into bile acids or excreted with the bile.
What are bile acids?
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
What does bile contain?
organic and inorganic (bile salts) components
Describe the production of bile.
- Produced by hepatocytes and passes into bile canaliculi
- Bile canaliculi carry bile back to the portal triad (opposite direction to blood)
Describe the role of bile in lipid digestion.
Bile facilitate solubilisation of dietary lipids during
digestion by micelle formation (promoting intestinal absorption of lipids)
Describe bilirubin metabolism in the liver?
- 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
What does the liver act as?
- Liver acts as gatekeeper between circulation and absorbed substances
- Liver principal site of metabolism
What is the first pass effect?
Substance absorbed from GI tract passes through liver
Describe the phase 1 reaction of drug metabolism.
- 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
Describe phase 2 reactions of drug metabolism.
- Conjugation with endogenous substrate to increase aqueous solubility
- Conjugation with glucoronide, sulfate, acetate, amino acid etc.
Describe transaminase enzymes - liver function assessments?
- 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
Describe cholestatic enzymes - liver function assessments.
- 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
Describe a foetal and newborn liver?
- 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
Describe the liver in childhood.
- Liver produces insulin-like growth factor-1 (IGF-1), hormone plays role in
childhood growth
Describe the liver in old people.
- Oxidative capacity of liver decreases with age
- Reduced metabolism: longer drug exposures and reduced toxin clearance
What are the mechanisms of drug induced liver injury?
- Direct hepatocyte damage
- Mitochondrial toxicity
- Metabolite activity
- Cholestasis
