liver, gall bladder and exocrine pancreas- physiology Flashcards
1
Q
what 3 cell types are sinusoids lined by?
A
- hepatic cells
- endothelial cells
- kupffer cells
2
Q
what drains into sinusoids?
A
blood from small portal venules
3
Q
what is the space of Disse?
A
region of space between endothelial cells and hepatic cells
4
Q
what is the function of the space of Disse?
A
- connects with lymphatic vessels in interlobular septa- excess fluid removal
- large pores in endothelium allow substances from plasma to diffuse freely- including plasma proteins
5
Q
what is the glucose buffer function of the liver?
A
can remove glucose from blood (to reduce blood glucose levels), store it, then release it (to raise blood glucose levels)
6
Q
what is gluconeogenesis?
A
formation of new glucose molecules from amino acids and glycerol (from triglycerides)
7
Q
what is the intermediate in the conversion of a fatty acid into acyl CoA?
A
acyl adenylate
8
Q
what enzyme promotes the conversion of acyl adenylate to acyl CoA?
A
acyl- CoA synthetase
9
Q
what 4 processes does an acyl CoA undergo to form acetyl CoA?
A
- oxidation- via acyl CoA dehydrogenase
- hydration- via enol- CoA hydrate
- oxidation- via hydroxyacyl CoA dehydrogenase
- thiolysis- via thiolase
10
Q
what happens to the acetyl CoA produced?
A
- 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
11
Q
what process is urea formed by?
A
asparto-arginosuccinate shunt
12
Q
why is there a constant turnover of proteins?
A
amino acids cannot be stored
13
Q
what is the daily renal excretion of amino acids?
A
70g/ day
14
Q
what is the faecal loss of amino acids each day?
A
10g/ day
15
Q
which type of cell absorbs amino acids and by what process does it do this?
A
- enterocytes
- via secondary active transport w/ Na+, Na+ concentration within the cell is maintained via Na+/ K+ pump
16
Q
what happens in transamination?
A
the process that takes an amino group from one amino acid and gives it to another alpha- ketoacid with a different R group
17
Q
what enzyme does transamination of alanine occur via?
A
alanine aminotransferase
18
Q
what is the function of ubiquitin?
A
- carboxyl group forms an isopeptide bond w/ multiple lysine residues
- formed by 3 enzymes
19
Q
what are the 3 enzymes in ubiquitin?
A
- E1- ubiquitin activating enzyme
- E2- ubiquitin conjugating enzyme
- E3- ubiquitin protein ligase
20
Q
how does a proteasome function?
A
- recognises ubiquitin- marked proteins
- contains proteolytic enzymes
- ends are capped- capped ends recognise ubiquitin makers and facilitate transport of protein into proteasome
21
Q
what 4 functions is a lysosome part of?
A
- macroautophagy
- microautophagy
- chaperone- mediated autophagy
- phagocytosis
22
Q
which molecule is the primary mode of protein breakdown- proteasome or lysosome?
A
proteasome
23
Q
what is the function of the glucose- alanine cycle?
A
to transport nitrogen from amino acid breakdown to the liver (via alanine)
24
Q
what is corresponding alpha- ketoacid to alanine?
A
pyruvate
25
what does alanine recycle?
carbon backbone and amino group containing nitrogen
26
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
27
what are xenobiotics?
foreign substances that are not produced in the body that have no nutritional value- need to be excreted
28
what must a substance be in order to be excreted?
water soluble
29
what is a phase 1 biotransformation reaction?
- non synthetic
- adds or exposes functional groups (-OH, -SH, -NH2, -COOH)
- small increase in hydrophilicity
30
what are the 3 main types of phase 1 reactions?
- oxidation
- reduction
- hydrolysis
31
what are the main phase 1 oxidation reactions?
- hydroxylation
- N- and O- dealkylation
- deamination
- epoxidation
- oxygen addition
- hydrogen removal
32
what are the main phase 1 reduction reactions?
- hydrogen addition
- oxygen removal
- donor molecules for these reactions include GSH, FAD, NAD(P)H
33
what are the main phase 1 hydrolysis reactions?
splitting of amide (C-N-C) and ester (C-O-C) bonds
34
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
35
what are examples of phase II reactions?
- glucuronidation (glycoside conjugation)
- sulphation
- methylation
- acylation (acetylation, amino acid conjugation, deacetylation)
- phosphate conjugation
36
what types of reaction of transferase enzymes mainly responsible for?
phase II reactions
37
where are cytochrome P450 enzymes found and what are they responsible for?
- smooth ER
| - phase I reactions
38
where are microsomal enzymes present?
smooth ER of liver, kidneys, lungs and intestinal mucosa
39
what reactions are microsomal enzymes responsible for?
- drug biotransformation reactions
| - oxidative, reductive, hydrolytic and glucuronidation
40
where are non microsomal enzymes found?
cytoplasm and mitochondria of hepatocytes and other tissues
41
what reactions are non microsomal enzymes responsible for?
non- specific enzymes that catalyse few oxidative, reductive and conjugation reactions
42
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
43
which enzyme catalyses the metabolism of ethanol?
alcohol dehydrogenase (ADH)
44
what is the other pathway by which ethanol can be metabolised?
microsomal ethanol oxidising system
45
how does ethanol cause liver damage?
- alcohol abuse= accumulation of acetaldehyde
- toxic
- forms adducts with amino acids- causes alcohol induced hepatitis
46
what does oxidation of acetaldehyde produce?
acetate and NADH + H+
47
what is paracetamol also known as?
acetaminophen
48
how is acetaminophen safely metabolised?
via glucuronidation or sulphation
49
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
50
what are the main functions of bile?
- lipid digestion and absorption
- cholesterol homeostasis
- excretion of lipid soluble xenobiotics, drug metabolites and heavy metals
51
how much bile is produced per day?
500-600mls/ day
52
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
53
what happens during the fasting stage of enterohepatic circulation?
bile acids acids travel down biliary tract to gall bladder
54
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
55
how are bile acids reabsorbed in the enterohepatic circulation?
via apical sodium bile acid transporter (ASBT) in the ileum
56
how many cycles of enterohepatic circulation occur during a meal?
2-3 cycles
57
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
58
what are bile acids synthesised from?
cholesterol
59
what are the 2 main primary bile acids synthesised from cholesterol?
- cholic acid
| - chenodeoxycholic acid
60
what does conjugation do to bile acids?
makes them more hydrophilic and acidic
61
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
62
why does emulsification occur?
- triglycerides insoluble in water
| - increases surface area for lipolysis
63
what does amphipathic mean?
- having both hydrophobic and hydrophilic parts
| - reduces surface tension and aids emulsification
64
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
65
what forms stercobilinogen from conjugated bilirubin?
intestinal bacteria
66
by what pathway does stercobilinogen form stercobilin?
oxidation
67
what compound gives faces its brown colour?
stercobilin
68
what is urobilinogen formed from?
stercobilinogen
69
how is urobilin formed?
oxidation of urobilinogen in the kidneys
70
what gives urine its yellow colour?
urobilin
71
what organelle produces pancreatic enzymes?
rough ER
72
why are granules secreted by acinar cells?
as precursors to protect the pancreas
73
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
74
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
75
what inhibits pancreatic enzyme secretion?
somatostatin
76
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
77
how is bicarbonate secretion controlled?
- low pH in small intestine
- increased secretin excretion
- increased HCO3- secretion
78
what inhibits bicarbonate secretion?
somatostatin
79
what are the 3 phases of pancreatic secretion?
- cephalic
- gastric
- intestinal
80
what happens during the cephalic phase?
- 20-25% of secretion
| - stimulation for cholinergic vagal input
81
what happens during the gastric phase?
- 10% secretion
| - vago-vagal reflex stimulate by gastric distention
82
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
83
what cells secrete CCK?
I cells
84
where is iron absorbed?
duodenum
85
how is iron lost?
- desquamation (loss of skin cells)
| - menstruation
86
what is the structure of ferritin?
- 24 covalently linked subunits
| - subunits form a shell around a central core containing up to 5000 iron atoms
87
where is ferritin found?
- mostly in cytoplasm of cells
| - some found in serum
88
what is the relationship between concentration of ferritin and total iron stores in the body?
proportional
89
what are the daily requirements of vitamin A?
- Male- 0.6mg/day
| - Female- 0.7mg/day
90
what are the functions of vitamin A?
- vision- forms rhodopsin
- reproduction- formation of spermatogenesis and prevention of foetal resorption
- growth
- stabilise cell membranes
91
what are the functions of vitamin D?
- increase intestinal absorption of Ca2+
- resorption and formation of bone
- reduce renal excretion of Ca2+
92
what are the daily requirements of vitamin E?
- Male- 4mg/ day
| - Female- 3mg/ day
93
what is the function of vitamin D?
antioxidant
94
what are the functions of vitamin K?
- activation of blood clotting factors
| - synthesis of clotting factors II, VII, IX, X
95
what vitamins are fat soluble?
ADEK
96
what vitamins are water soluble?
C, B12, folate
97
what are the functions of vitamin C?
- collagen synthesis
- antioxidant
- iron absorption
98
what are the 2 forms of vitamin B12?
- methylcobalamin
| - 5- deoxyadenosylcobalamin
99
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
100
what is the function of folate?
- coenzyme in methylation reactions
- DNA synthesis
- synthesis of methionine from homocysteine
101
how is the intrinsic clotting pathway activated?
contact
102
how is the extrinsic clotting pathway activated?
by FVII coming in contact w/ tissue factor
103
which clotting factors are produced by the liver?
I (fibrinogen), II (prothrombin), IV, V, VI, VII
104
how is the performance of the extrinsic pathway measured?
prothrombin time
105
how is the performance of the intrinsic pathway measured?
activated partial thromboplastin time (aPTT)
106
where does the liver develop?
ventral mesentery
107
where does the spleen develop?
dorsal mesentery
108
what are the liver and endo & exocrine pancreas developed from?
endoderm
109
what is the connective tissue of the pancreas and liver derived from?
visceral mesoderm
110
where in the foregut do the liver and 2 pancreatic buds develop from?
duodenum
111
what attaches the liver to the anterior abdominal wall?
falciform ligament
112
what does the dorsal pancreatic bud form?
head, neck, body and tail
113
what does the ventral pancreatic bud form?
uncinate process
114
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
