liver, gall bladder and exocrine pancreas- physiology Flashcards
what 3 cell types are sinusoids lined by?
- hepatic cells
- endothelial cells
- kupffer cells
what drains into sinusoids?
blood from small portal venules
what is the space of Disse?
region of space between endothelial cells and hepatic cells
what is the function of the space of Disse?
- connects with lymphatic vessels in interlobular septa- excess fluid removal
- large pores in endothelium allow substances from plasma to diffuse freely- including plasma proteins
what is the glucose buffer function of the liver?
can remove glucose from blood (to reduce blood glucose levels), store it, then release it (to raise blood glucose levels)
what is gluconeogenesis?
formation of new glucose molecules from amino acids and glycerol (from triglycerides)
what is the intermediate in the conversion of a fatty acid into acyl CoA?
acyl adenylate
what enzyme promotes the conversion of acyl adenylate to acyl CoA?
acyl- CoA synthetase
what 4 processes does an acyl CoA undergo to form acetyl CoA?
- oxidation- via acyl CoA dehydrogenase
- hydration- via enol- CoA hydrate
- oxidation- via hydroxyacyl CoA dehydrogenase
- thiolysis- via thiolase
what happens to the acetyl CoA produced?
- some metabolised in liver via TCA cycle
- excess acetyl CoA converted into acetoacetic acid- which passes into the ECF and is absorbed by other tissues, converted back into acetyl CoA and is metabolised
what process is urea formed by?
asparto-arginosuccinate shunt
why is there a constant turnover of proteins?
amino acids cannot be stored
what is the daily renal excretion of amino acids?
70g/ day
what is the faecal loss of amino acids each day?
10g/ day
which type of cell absorbs amino acids and by what process does it do this?
- enterocytes
- via secondary active transport w/ Na+, Na+ concentration within the cell is maintained via Na+/ K+ pump
what happens in transamination?
the process that takes an amino group from one amino acid and gives it to another alpha- ketoacid with a different R group
what enzyme does transamination of alanine occur via?
alanine aminotransferase
what is the function of ubiquitin?
- carboxyl group forms an isopeptide bond w/ multiple lysine residues
- formed by 3 enzymes
what are the 3 enzymes in ubiquitin?
- E1- ubiquitin activating enzyme
- E2- ubiquitin conjugating enzyme
- E3- ubiquitin protein ligase
how does a proteasome function?
- recognises ubiquitin- marked proteins
- contains proteolytic enzymes
- ends are capped- capped ends recognise ubiquitin makers and facilitate transport of protein into proteasome
what 4 functions is a lysosome part of?
- macroautophagy
- microautophagy
- chaperone- mediated autophagy
- phagocytosis
which molecule is the primary mode of protein breakdown- proteasome or lysosome?
proteasome
what is the function of the glucose- alanine cycle?
to transport nitrogen from amino acid breakdown to the liver (via alanine)
what is corresponding alpha- ketoacid to alanine?
pyruvate
what does alanine recycle?
carbon backbone and amino group containing nitrogen
what does alanine form along with alpha-ketoglutarate via alanine aminotransferase in the hepatocyte?
pyruvate and glutamate- glutamate broken down to urea to excrete the nitrogen
what are xenobiotics?
foreign substances that are not produced in the body that have no nutritional value- need to be excreted
what must a substance be in order to be excreted?
water soluble
what is a phase 1 biotransformation reaction?
- non synthetic
- adds or exposes functional groups (-OH, -SH, -NH2, -COOH)
- small increase in hydrophilicity
what are the 3 main types of phase 1 reactions?
- oxidation
- reduction
- hydrolysis
what are the main phase 1 oxidation reactions?
- hydroxylation
- N- and O- dealkylation
- deamination
- epoxidation
- oxygen addition
- hydrogen removal
what are the main phase 1 reduction reactions?
- hydrogen addition
- oxygen removal
- donor molecules for these reactions include GSH, FAD, NAD(P)H
what are the main phase 1 hydrolysis reactions?
splitting of amide (C-N-C) and ester (C-O-C) bonds
what is a phase II biotransformation reaction?
- biosynthetic
- conjugation with endogenous molecules
- e.g. glucoronic acid, sulphate, glutathione
- covalent bonds formed
- large increase in hydrophilicity
what are examples of phase II reactions?
- glucuronidation (glycoside conjugation)
- sulphation
- methylation
- acylation (acetylation, amino acid conjugation, deacetylation)
- phosphate conjugation
what types of reaction of transferase enzymes mainly responsible for?
phase II reactions
where are cytochrome P450 enzymes found and what are they responsible for?
- smooth ER
- phase I reactions
where are microsomal enzymes present?
smooth ER of liver, kidneys, lungs and intestinal mucosa
what reactions are microsomal enzymes responsible for?
- drug biotransformation reactions
- oxidative, reductive, hydrolytic and glucuronidation
where are non microsomal enzymes found?
cytoplasm and mitochondria of hepatocytes and other tissues
what reactions are non microsomal enzymes responsible for?
non- specific enzymes that catalyse few oxidative, reductive and conjugation reactions
why is ethanol not metabolised via phase I and II reactions?
- does not need to be conjugated for excretion
- only up to 10% os excreted- rest is used in liver as a dietary fuel
which enzyme catalyses the metabolism of ethanol?
alcohol dehydrogenase (ADH)
what is the other pathway by which ethanol can be metabolised?
microsomal ethanol oxidising system
how does ethanol cause liver damage?
- alcohol abuse= accumulation of acetaldehyde
- toxic
- forms adducts with amino acids- causes alcohol induced hepatitis
what does oxidation of acetaldehyde produce?
acetate and NADH + H+
what is paracetamol also known as?
acetaminophen
how is acetaminophen safely metabolised?
via glucuronidation or sulphation
how can overdosing on acetaminophen cause liver damage?
- produces NAPQI as an intermediate
- NAPQI accumulates
- toxic- causes damage to hepatocytes
- metabolism of NAPQI is not proportionate to production of NAPQI when present in excess
what are the main functions of bile?
- lipid digestion and absorption
- cholesterol homeostasis
- excretion of lipid soluble xenobiotics, drug metabolites and heavy metals
how much bile is produced per day?
500-600mls/ day
what is enterohepatic circulation?
- allows a bile-acid pool
- as rate of synthesis of bile is limiting- therefore previously produced bile has to be recycled in order to meet the body’s needs
what happens during the fasting stage of enterohepatic circulation?
bile acids acids travel down biliary tract to gall bladder
what happens during the fed stage of enterohepatic circulation?
- CCK released from duodenal mucosa
- CCK relaxes sphincter of Oddi and contracts gall bladder
- fat absorption
- GB remains contracted during digestion- targeting synthesised bile acid directly into the gut
how are bile acids reabsorbed in the enterohepatic circulation?
via apical sodium bile acid transporter (ASBT) in the ileum
how many cycles of enterohepatic circulation occur during a meal?
2-3 cycles
what happens in the interdigestive stage of enterohepatic circulation?
sphincter of Oddi contracts and gall bladder relaxes- encourages secreted bile to enter the gall bladder
what are bile acids synthesised from?
cholesterol
what are the 2 main primary bile acids synthesised from cholesterol?
- cholic acid
- chenodeoxycholic acid
what does conjugation do to bile acids?
makes them more hydrophilic and acidic
what are the functions of bile acids?
- induce bile flow via HCO3- secretion
- induce secretion of biliary lipids
- digestion of dietary fats
- facilitate protein absorption- accelerate hydrolysis by pancreatic proteases
- cholesterol homeostasis
- antimicrobial
- prevents gallstones
why does emulsification occur?
- triglycerides insoluble in water
- increases surface area for lipolysis
what does amphipathic mean?
- having both hydrophobic and hydrophilic parts
- reduces surface tension and aids emulsification
which enzyme acts on bilirubin in the hepatocyte to form bilirubin diglucoronide?
- UDP glucoronyl transferase
- acts twice- each time adding glucoronic acid
- forms conjugated bilirubin
what forms stercobilinogen from conjugated bilirubin?
intestinal bacteria
by what pathway does stercobilinogen form stercobilin?
oxidation
what compound gives faces its brown colour?
stercobilin
what is urobilinogen formed from?
stercobilinogen
how is urobilin formed?
oxidation of urobilinogen in the kidneys
what gives urine its yellow colour?
urobilin
what organelle produces pancreatic enzymes?
rough ER
why are granules secreted by acinar cells?
as precursors to protect the pancreas
what is the mechanism for secretion of pancreatic enzymes?
- rise in intracellular Ca2+- due to ACh stimulation, gastrin and CCK
- exocytosis of vacuoles
- acinar cells secrete a small volume of isotonic fluid to wash enzymes into ducts
what is the control mechanism of pancreatic enzyme secretion?
- presence if fatty acids and amino acids in small intestine
- increased CCK secretion
- increased enzyme secretion
what inhibits pancreatic enzyme secretion?
somatostatin
what causes the movement of water into the pancreatic lumen?
movement of Na+ and HCO3- into lumen forms an osmotic pressure gradient- therefore promoting the movement of water
how is bicarbonate secretion controlled?
- low pH in small intestine
- increased secretin excretion
- increased HCO3- secretion
what inhibits bicarbonate secretion?
somatostatin
what are the 3 phases of pancreatic secretion?
- cephalic
- gastric
- intestinal
what happens during the cephalic phase?
- 20-25% of secretion
- stimulation for cholinergic vagal input
what happens during the gastric phase?
- 10% secretion
- vago-vagal reflex stimulate by gastric distention
what happens during the intestinal phase?
- 60-70% secretion
- endocrine action of secretin on ductular cells
- CCK, ACh and GRP (gastrin releasing peptide) action on acinar cells
- enteropancreatic reflex mediated by enteric nervous system- amplifies response
what cells secrete CCK?
I cells
where is iron absorbed?
duodenum
how is iron lost?
- desquamation (loss of skin cells)
- menstruation
what is the structure of ferritin?
- 24 covalently linked subunits
- subunits form a shell around a central core containing up to 5000 iron atoms
where is ferritin found?
- mostly in cytoplasm of cells
- some found in serum
what is the relationship between concentration of ferritin and total iron stores in the body?
proportional
what are the daily requirements of vitamin A?
- Male- 0.6mg/day
- Female- 0.7mg/day
what are the functions of vitamin A?
- vision- forms rhodopsin
- reproduction- formation of spermatogenesis and prevention of foetal resorption
- growth
- stabilise cell membranes
what are the functions of vitamin D?
- increase intestinal absorption of Ca2+
- resorption and formation of bone
- reduce renal excretion of Ca2+
what are the daily requirements of vitamin E?
- Male- 4mg/ day
- Female- 3mg/ day
what is the function of vitamin D?
antioxidant
what are the functions of vitamin K?
- activation of blood clotting factors
- synthesis of clotting factors II, VII, IX, X
what vitamins are fat soluble?
ADEK
what vitamins are water soluble?
C, B12, folate
what are the functions of vitamin C?
- collagen synthesis
- antioxidant
- iron absorption
what are the 2 forms of vitamin B12?
- methylcobalamin
- 5- deoxyadenosylcobalamin
how is vitamin B12 released from food and absorbed?
- via stomach acid
- binds to R protein to protect from damage via stomach acid
- released from R protein by pancreatic polypeptide
- intrinsic factor required for absorption
- IF-B12 complex absorbed in terminal ileum
- B12 stored in liver
what is the function of folate?
- coenzyme in methylation reactions
- DNA synthesis
- synthesis of methionine from homocysteine
how is the intrinsic clotting pathway activated?
contact
how is the extrinsic clotting pathway activated?
by FVII coming in contact w/ tissue factor
which clotting factors are produced by the liver?
I (fibrinogen), II (prothrombin), IV, V, VI, VII
how is the performance of the extrinsic pathway measured?
prothrombin time
how is the performance of the intrinsic pathway measured?
activated partial thromboplastin time (aPTT)
where does the liver develop?
ventral mesentery
where does the spleen develop?
dorsal mesentery
what are the liver and endo & exocrine pancreas developed from?
endoderm
what is the connective tissue of the pancreas and liver derived from?
visceral mesoderm
where in the foregut do the liver and 2 pancreatic buds develop from?
duodenum
what attaches the liver to the anterior abdominal wall?
falciform ligament
what does the dorsal pancreatic bud form?
head, neck, body and tail
what does the ventral pancreatic bud form?
uncinate process
why are the superior mesentery artery and vein located infront of the uncinate process?
ventral pancreatic bud loops behind them during development before fusing with the dorsal pancreatic bud
