Hepatic System Flashcards
What is the largest gland + largest internal organ in the body ?
- the liver
How many lobes does the liver contain ?
- 4 lobes
- 2 Major (Left & Right) -largest
- 2 Minor (Caudate & Quadrate)
What is the liver covered by ?
- a single layer of mesothelium
Where is the gall bladder located in relation to the liver ?
- under the right lobe
What is one of the primary functions of the liver ?
- Functions as exocrine gland – bile secretion
What is a liver lobule composed of ?
– Central terminal hepatic venule
– Interconnecting plates of hepatocytes
– Peripherally arranged portal triad (hepatic artery, portal vein and bile duct )
What are the hepatocyte zones ?
- centrilobular, periportal, mid zone
What 2 vessels does liver receive its blood from ?
- hepatic portal vein
- hepatic artery
What is the function of the hepatic portal vein ?
- blood to the liver, 75% blood supply to liver
- nutrient rich blood from digestive tract and spleen
- filters toxins from digestive tract
What is the function of the hepatic artery ?
- Oxygenated blood from aorta
• 25% Blood Supply
What are the sinusoids in the liver ?
- endothelium lined spaces in lobule, replacing capillaries
What are the sinusoids partly lined with and what is their function ?
- lined with Kupffer cells (phagocytes)
- function is to destroy bacteria + worn-out blood cells
What are hepatic stellate cells function + location ?
• Pericytes found in space of Disse (perisinusoidal space)
• Retinoid storage (in lipid droplets)
What does damage to hepatic stellate cells lead to ?
- leads to transdifferentiation into proliferative fibrogenic myofibroblasts and liver fibrosis
What percentage of hepatocyte surface area faces sinusoid ?
- 70% to maximise blood exchange
What percentage of hepatocyte surface area faces bile canaliculi ?
- 15%
What happens to bile canaliculi in the liver ?
- merge into bile ductless, running alongside portal veins
What are the main functions of the liver ?
- Xenobiotic detoxification and metabolism
• Decomposition of erythrocytes and excretion of bilirubin
• Bile Production
• Cholesterol synthesis and Lipogenesis
• Carbohydrate Metabolism
What proteins does the liver synthesise ?
- Albumin (major osmolar component of blood serum)
• Coagulation factors : fibrinogen, prothrombin, factors (V, VII, IX-XI), antithrombin
What hormones does the liver produce ?
• Thrombopoietin (regulates platelet production by bone marrow)
• Angiotensin (raises blood pressure following renin activation)
What does the liver store ?
• Glycogen
• Vitamins A, D, E, K (fat soluble), B12 (water soluble)
• Iron, Copper
What happens when there is a decline in glucose level ?
- glycogenolysis = glycogen —-> glucose
- if glycogen exhausted = gluconeogenesis
What is the Cori cycle ?
- lactate converted to glucose
what is the alanine cycle ?
- Degradation of proteins - amino groups transferred to pyruvate
- giving rise to alanine, which is transported to the liver
- it’s carbon skeleton is converted into glucose
How does the liver convert glucose into fatty acids ?
- via acetyl-CoA, which is then used to form fatty acids
What does the liver do with fatty acids supplied from intestine ?
- receives fatty acids from lipids in chylomicrons from intestine
- converted into neutral fats and phospholipids
What percentage of cholesterol is produced by the liver ?
- 70%
What is cholesterol used for ?
- synthesis of bile acids
- cells 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 form cholesterol
What does it mean when bile acids are amphipathic ?
- have a polar and a polar side , act as detergents
How do bile acids form bile salts ?
- linked to amino acids
What components are found in bile ?
- organic = bilirubin
- inorganic = bile salts
Where is bile produced and how does it move within the liver ?
- produced by hepatocytes
- Bile canaliculi carry bile back to the portal triad (opposite direction to blood)
How does bile aid in lipid digestion ?
- bile facilitates solubilisation of lipids by forming micelles which can be absorbed by the intestines
What happens to erythrocytes and the end of their life span ?
- phagocytosed haemoglobin released
- blobs metabolised + amino acids recycled
- iron bound to transferrin + returned to liver
- Haem converted to bilirubin, bound to albumin
How is bilirubin metabolised in the liver ?
- 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. - Intestinal bacteria degrade bilirubin to urobilinogen
- 80% oxidised to stercobilin and excreted in faeces
• 20% enters extrahepatic circulation and excreted in urine
What role does the liver replay in biotransformation + metabolism ?
- acts as against gatekeeper between circulation + absorbed substances from the GI tract
- metabolizing both natural and foreign substances (e.g., drugs).
What is the first pass effect in metabolism ?
- after absorption from the GI tract, a significant portion of a substance may be metabolically inactivated in the liver before it reaches circulation, making dosage important.
What happens during phase I reactions of drug metabolism ?
- make parent compound more polar by adding or unmasking functional groups
What happens during phase II reactions ?
• Conjugation with endogenous substrate to increase aqueous solubility
• Conjugation with glucoronide, sulfate, acetate, amino acid etc.
What is an example of a phase I reactions ?
- Oxidation Reactions (Cytochrome P450’s):
- Oxygen incorporated into drug
- Oxidation causes loss of part of drug
What are 2 examples of substrates for Cyt P450 isozymes ?
- caffeine
- estradiol
What is an example of phase II reactions ?
- Glucuronidation- UDP-Glucuronosyltransferase:(-OH, -COOH, -NH2,-SH)
What is Hepatitis ?
- inflammation of liver
What is Cirrhosis ?
- formation of fibrous tissue in liver replacing dead cells
What is Haemochromatosis ?
- excessive iron accumulation and liver damage
What are Hepatic system cancers ?
- hepatocellular carcinoma
- cholangiocarcinoma
What is Wilson’s disease ?
- hereditary disease causing copper retention
What is Biliary cirrhosis ?
- disease of small bile ducts
What is Gilbert’s syndrome ?
- genetic disorder of bilirubin metabolism
What is Jaundice ?
- Yellow coloured skin, nail beds & sclera caused by deposition of bilirubin due to hyperbilirubinemia
What is the role of Alanine aminotransferase (ALT) is liver function tests ?
- Increased when cells of the liver are inflamed or undergo cell death
- Rises dramatically in acute liver damage, such as viral hepatitis
What is the significance of Aspartate aminotransferase (AST) in liver function tests?
- AST is raised in acute liver damage, but it is less specific for liver disease compared to ALT.
What does Alkaline Phosphatase (ALP) indicate in liver function assessment?
- Raised in biliary tract damage and inflammation, indicating issues with bile flow
What is the role of Gamma-Glutamyl Transferase (GGT) in liver function tests ?
- Produced by the bile duct (sensitive marker for cholestatic damage)
- Raised in alcohol toxicity
How is bilirubin used in liver function assessments?
- measured in plasma total and direct (conjugated) forms
- Urine may show urobilinogen and bilirubin levels, indicating liver or bile duct function.
What is paediatric jaundice and why does it occur?
- occurs in newborns due to low levels of bilirubin glucuronyl transferase in the liver, causing inefficient conjugation of bilirubin.
How does the liver function in childhood?
- liver produces insulin-like growth factor-1 (IGF-1), a hormone important for growth during this period.
What age-related changes occur in the liver during geriatrics?
- the liver’s oxidative capacity decreases,
- leading to reduced metabolism, longer drug exposures, and decreased toxin clearance.
