B3 W2 Flashcards
What contributes to chylomicron formation?
Apoproteins which binds to re-esterified lipids
What is the fast phase?
Transfer between the central and peripheral compartments. The Cp after this can be used to obtain the Vd of both compartments.
How to obtain estimate of rate of elimination?
Half life of slow phase
What is the limitation of single compartment model?
Drugs are not equally soluble across all tissues. Assumes Cp is directly proportional to rate of excretion and metabolism.
What is saturation kinetics?
Enzymatic reactions where maximum rate of reaction occurs when there is 100% enzyme saturation.
What are the implications of saturation?
Dose and duration of action are equal. Dose and Cp are not proprotional. This causes non-linear kinetics. The maximum rate of metabolism sets a limit for drug clearance where after a certain point, Cp can continue to increase. This makes it difficult to administer
What is saturation kinetics?
Aka zero order kinetics. A constant amount of drug is eliminated per unit of time. The rate of elimiation is independent of the drug conc. A higher concentration will not result in a greater rate of eliminate. Zero-order drugs undergo zero-order kinetics.
What is the model of saturation kinetics?
Relationship between dose and Cp is unpredictable
What is a first order kinetics?
Rate of elimination of a drug is proportional to drug conc Higher concentration of drug means higher rate of elimination. Aspirin has first order kinetics.
What is the exogenous pathway?
Chylomicrons are assembled which travel via the lacteal duct system and enters the bloodstream to unload fats at the peripheral tissues. The fats can be used as adipose stores or energy via triglycerides. The chylomicron remnant returns to the liver and binds to apoE receptor.
What is lipoprotein lipase?
An extracellular enzyme found in vascular endothelium, muscle and adipose tissue which metabolises triglycerides of VLDL and chylomicrons -> fatty acids + glycerol. Chylomicron remnants are taken up by the liver via endocytosis.
What is the endogenous pathway?
More triglycerides is packaged into VLDL which travels to the peripheral tissue. It is metabolised by lipoprotein lipase and forms IDL and empty HDL. IDL is absorbed by the liver and metabolised by hepatic lipase into LDL. LDL circulates more cholesterol and is absorbed by tissues via LDL receptors
Reticuloendothelial system
Phagocytes and monocytes in the organs. Involves the Kuppfer cells of liver, microglia of brain, alveolar macrophages and bone marrow lymph nodes. Eg, phagocytic destruction of RBC and metabolism of iron and pigment
Hmg-coA reductase
Enzyme which is a rate-limiting factor in cholesterol synthesis. Catalyses acetylcoA into isopentenyl pyrophosphate -> squalene -> cholesterol
Falciform ligament
Liver ligament which suspends it from the diaphragm and separates it into a left and right lobe
Beta oxidation
Metabolism of fatty acid into a 2-carbon fragment which enters citric acid cycle as acetyl coA
Cholesterol esterase
Metabolises cholesterol ester into cholesterol and fatty acid
Phase 1 metabolism
Cytochrome P450 enzyme metabolises drug into a polar inactive metabolite. This is through oxidation, hydrolysis, hydroxylation and deamination
Phase 2 metabolism
Conjugation of a drug to make it more polar and easily excretable
What is the blood supply to the caudate and quadrate lobes?
Left hepatic artery
Hepatic veins
Transports blood from liver to inferior vena cava
What vessel transports blood from the liver to vena cava?
Hepatic vein
Ketaconazole and Terfenadine
Inhibits cytochormame P450 for phase 1 metabolism of drug. This increases Cp of the drug
Perivenous end
Lower oxygen conc closest to the central vein. Site of glycolysis, glycogenolysis, lipogenesis, ketogenesis and glutamine and bile acid biosynthesis. Drug metabolism phase 1 and phase 2 (conjugation) occur here
Periportal end
Higher oxygen conc for gluconeogenesis, cholesterol and urea biosynthesis and beta oxidation
Absorptive state
Catabolism exceeds anabolism following a meal. Storage of molecules is high; Liver converts glucose to acetyl coA and fatty acids for storage. Lipogenesis, glycogenesis occurs
Deepest part of abdominal cavity when in supine position
Hepatorenal recess
Location of hepatoduodenal ligament
Between the porta hepatis and sueprior duodenum
Types of lipoproteins
Chylomicrons, VLDL, LDL and HDL
How do statins work?
Targets HMG-coA reductase
What is the major blood supply to the liver?
Hepatic portal vein
Xenobiotics
Foreign substances
What are the routes of drug excretion?
Via urine, faeces, breast milk, sweat and air
How does cholesterol synthesis occur?
HMG-coA reductase converts acetyl coA -> isopentenyl pyrophosphate. 6x produces squalene -> cholesterol
Where does phase 1 and 2 metabolism occur in the liver?
Perivenous end
What is the liver function test?
Bilirubin, albumin and prothrombin time to indicate liver damage via the levels
How is cholesterol excreted in the faeces?
In the form of coprostanol by bacteria
Prothrombin time
Assess time for coagulation, dependent on the health of the liver
Apoproteins
Proteins on surface of lipoproteins which allows the packaging of lipids into chylomicrons
Which level is the gall bladder?
Tip of 9th costal cartilage
Lecithin-cholesterol acyltransferase
Catalyses esterification of cholesterol to form mature HD
Liver channels
Sinusoids
How do micelles enter enterocytes?
NPC1L1 channels
Where the bile duct and arties enter the liver
porta hepatis
Cytochrome P450
Drug involved in metabolism which contains iron for accepting/donating electrons to make the drug more or less polar. It is stored in the SER of hepatocytes
How does HDL transfer lipids?
Via cholesterol ester transferase enzyme catalyses the transfer of cholesterol ester from HDL to VLDL and chylomicrons. This is taken up by the liver.
Sterol responsive element binding protein?
Transcription factor which regulates cholesterol synthesis. It is attached to the cell membrane and remains when cholesterol is high. When cholesterol is low, it detaches.
Omental foramen
Epiploic foramen/foramen of winslow.
Scavenger receptor class B1
Allows HDL to be taken up by the liver
What carries bile from the liver and gallbladder to the hepatopancreatic ampulla?
Common bile duct
Chyle
White fatty substance in lymph consisting of fat absorbed by lacteals
What are the features of low albumin?
Albumin is synthesised by the liver and creates colloid osmotic pressure for reabsorption; osmotic pressure is low and fluid will accumulate in the interstitial space
What is the clinical features of liver disease?
Fluid oedema, thrombocytopenia, excessive bleeding, haemhorrage,
What is cholestasis?
Post hepatic jaundice caused by reduced bile flow from the liver and lead to CONJUGATED ONLY bilirubin entering bloodstream. This can occur due to primary cause such as cirrhosis or secondary due to bile duct obstruction and results in dark urine and pale stools
What is the indication of dark urine and pale stool?
Dark urine is due to bilrubin in the form of urobilinogen; pale stools is due to absence of bile pigments. This is caused by cholestasis due to liver obstruction
Why are stools pale?
Due to absence of bile pigment urobilinogen which is converted -> stercobilin and gives stools a brown colour
How are bile pigments produced?
Decomposition of the porphyrin ring via haemolysis to form biliverdin in the spleen. Biliverdin is reduced to form bilirubin. Bilirubin undergoes conjugation in the liver for safe excretion. Bilirubin is converted to urobilinogen by bacteria in the large intestine for excretion in the faeces.
Where are bile pigments excreted?
Mainly in the faeces as stercobilin and lesser in the urine as urobilinogen
How does the liver alter bile pigments?
Bile pigments such as bilirubin are conjugated to be excreted through the bile. This enters the intestine through the bile ducts.
How is bilirubin excreted?
It is deconjugated by B-glucuronidase enzyme. Intestinal bacteria cause bilirubin-> urobilinogen which re-enters the blood to be excreted in urine. and reabsorbed into enterohepatic circulation and is excreted in stools as stercobilin.
Pre-hepatic jaundice
Caused by haemolytic anaemia which may be immune system disorder or caused by an infectious disease. This results in excess production of biliverdin-> bilirubin. The excess unconjugated bilirubin leads to dark urine and pale stools
How is bilirubin formed?
From reduction of biliverdin-> bilirubin, catalysed by biliverdin reductase
Foregut
Pharynx, oesophagus, gallbladder, Stomach, liver, pancreas, spleen, proximal duodenum. Lungs develop from the evagination of the foregut.
Midgut
Distal duodenum, jejunum, ileum, caecum, veriform appendix, ascending colon, 1/3 of transverse colon
Hindgut
Distal 1/3 transverse colon, descending colon, sigmoid colon, rectum and proximal anal canal
Blood supply to the foregut
Coeliac trunk
Blood supply to midgut
Superior mesenteric artery
Blood supply to hindgut
Inferior mesenteric artery
Pouches which form the large intestine
Haustra
Anocutaneous line
Change in epithelia from keratinising to non keratinising stratified squamous. After the pectinate line, where before this, it is simple columnar
Germ layer for outer skin layer
Ectoderm
Re-esterfication
Products of lipid digestion form phospholipid, trialglycerol and cholesterol.
Peritoneal recesses
Gutter where peritoneum drapes over the viscera
