Hepatic System Flashcards
What is the hepatic system?
Liver + gall bladder
What is the structure of the liver?
Highly vascularised 4 lobes = 2 major + 2 minor Well defined thin capsule of connective tissue Rich in nerve endings Covered by single layer of mesothelium
What are the 2 major lobes?
Left & right
What are 2 minor lobes?
Caudate & quadrate
What is the function of gall bladder?
Bile storage + secretion
Where is gall bladder?
Under right lobe of liver
What is the liver lobule?
Functional unit of the liver
What is liver lobule structure?
Specialised epithelial cells + hepatocytes
What is the liver lobule composed of?
Central terminal hepatic venule
Interconnecting places of hepatocytes
Peripherally arranged portal triad
What are the hepatocyte zones in liver lobule?
Centrilobular, periportal + mid zone
What are the 2 vessels the liver receives blood form?
Hepatic portal vein
Hepatic artery
What does the portal vein do?
Conducts blood to liver + NOT directly to heart
Nutrient rich blood from digestive tract + spleen
Filters toxins from digestive tract
What percentage of blood does portal vein supply to the liver?
75%
What does the hepatic artery do?
Oxygenated blood supply from aorta
What percentage of blood does hepatic artery supply to the liver?
25%
Does the liver lobule have capillaries?
NO
What does the portal vein + hepatic artery discharge into?
Liver sinusoids
What are the liver sinusoids lined with and why?
Phagocytes (Kupffer cells)
= destroy bacteria
Where are pericytes found in sinusoids?
Disse (perisinusoidal space)
What is stored in sinusoids?
Retinoid
What does damage of sinusoids lead to?
Transdifferentiation into proliferative fibrogenic myofibroblasts + liver fibrosis
What does bile canaliculi coalesce into?
Bile ductiles, running alongside portal veins
Does blood + bile flow in opposite directions?
YES
What are functions of the liver?
Detoxification + metabolism Decomposition of erythrocytes + excretion of bilirubin Cholesterol synthesis + lipogenesis Carbohydrate metabolism Protein synthesis Hormone production
What does the liver store?
Glycogen
Vitamin A, D, E, K + B12
Fe
Cu
What is glycogenesis?
Synthesis of glycogen from excess glucose-6-phosphate
What happens in glycogenesis?
Glucose converted to G6P using 1x ATP G6P converted to G1P Activated by UTP=UTP-glucose UTP-glucose attaches to end of glucose chain UDP released (converted to UTP using ATP)
What happens in glycogenolysis?
Glucose phosphorylated when cleaved from glycogen to form G1P
G1P —-> G6P, which enters glycolysis
Phosphorylated glucose can’t enter cells
G6P hydrolysed to glucose
What is glycogenolysis activated by?
Glucagon in liver
What is glycogenolysis inhibited by?
Insulin
What is gluconeogenesis?
Glucose from non-carbohydrates
What molecules are considered glucogenic?
Any that can be converted to pyruvate
eg. lactate, alanine, glycerol
What is is the process of gluconeogenesis?
Reversible reactions of glycolysis
What 3 reactions are not reversible?
Hexokinase
Phosphofructokinase
Pyruvate kinase
What pathway is gluconeogenesis?
Red enzyme gluconeogenic pathway
What do red enzymes do?
Overcome high negative free energy of irreversible reactions of glycolysis
What is the Cori cycle?
Flow of lactate + glucose between muscles + liver
What happens in Cori cycle?
Lactate oxidised back t pyruvate in liver
Gluconeogenesis converts pyruvate to glucose
Transferred to muscles
What happens in liver metabolism?
Liver converts glucose via acetyl-CoA into fatty acids
Retrieves FAs from lipids supplied with chylomicrons from intestine
Converted into neutral fats + phospholipids
VLDL formed
What is cholesterol used for?
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 liver from cholesterol
What is bile produced by?
Hepatocytes and passes into bile canaliculi
Where does bile canaliculi carry bile back to?
Portal triad
What is lipid digestion?
Bile facilitate solubilisation of dietary lipids during digestion by micelle formation
How is bilirubin formed?
Phagocytised + haemoglobin released
Describe process of bilirubin formation
Globin metabolised + amino acid recycled
Fe bound to transferrin + returned to liver & BM
Haem converted to bilirubin, bound to albumin
How is bilirubin metabolised in the liver?
Uptake of bilirubin by hepatocytes
Bilirubin conjugated with 2 glucuronic acids by UDP -glucuronyl transferase
Conjugate bilirubin transported into bile canaliculi + bile
Intestinal bacteria degrade bilirubin + urobilinogen
What happens to bilirubin after it has been degraded?
80% oxidised to stercobilin + excreted in faeces
20% enters extrahepatic circulation + excreted in urine
What is the first pass effect?
Substance absorbed from GI tract passes through liver
What are phase I reactions?
Metabolism
Describe what happens in phase I reactions
Convert parent compound into more polar molecule
By adding or unmasking functional group
Often metabolites inactive
Describe what happens in phase II reactions
Conjugation with endogenous substrate to increase aq solubility
Conjugation with glucoronide, sulfate, acetate + amino acid
When do transaminases enzymes increase?
When liver is inflamed + damaged
When do cholestatic enzymes increase?
When biliary tract damaged + inflamed
Describe liver at foetal + newborn
1st trimester, liver main site of RBC production
By 32 weeks BM takes over
Describe liver at childhood
Liver produces insulin-like growth factor
Hormones plays role in childhood growth
Describe geriatric liver
Oxidative capacity of liver decreases with age
Reduced metabolism = longer drug exposure + reduced toxin clearance
What is hepatitis?
Inflammation of liver
What is cirrhosis?
Formation of fibrous tissue in liver replacing dead cells
What is haemochromatosis?
Excessive iron accumulation + liver damage
What is hepatic system cancer?
Hepatocellular carcinoma, cholangiocarcinoma
What is Wilson’s disease?
Hereditary disease causing copper retention
What is biliary syndrome?
Genetic disorder of bilirubin metabolism
What is jaundice?
Yellow coloured skin, nail beds & sclera caused by deposition of bilirubin due to hyperbilirubinemia
What are the three types of jaundice?
Haemolytic
Obstructive
Hepatocellular
What is haemolytic jaundice?
Excessive RBC lysis
What is obstructive jaundice?
Conjugated bilirubin prevented from entering intestine
What is hepatocellular jaundice?
Liver damage causes low conjugation efficiency