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Nicks phase 1 flashcards > liver, gall bladder and exocrine pancreas- physiology > Flashcards

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
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2
Q

what drains into sinusoids?

A

blood from small portal venules

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3
Q

what is the space of Disse?

A

region of space between endothelial cells and hepatic cells

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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
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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)

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6
Q

what is gluconeogenesis?

A

formation of new glucose molecules from amino acids and glycerol (from triglycerides)

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7
Q

what is the intermediate in the conversion of a fatty acid into acyl CoA?

A

acyl adenylate

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8
Q

what enzyme promotes the conversion of acyl adenylate to acyl CoA?

A

acyl- CoA synthetase

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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
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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
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11
Q

what process is urea formed by?

A

asparto-arginosuccinate shunt

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12
Q

why is there a constant turnover of proteins?

A

amino acids cannot be stored

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13
Q

what is the daily renal excretion of amino acids?

A

70g/ day

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14
Q

what is the faecal loss of amino acids each day?

A

10g/ day

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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

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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

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17
Q

what enzyme does transamination of alanine occur via?

A

alanine aminotransferase

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18
Q

what is the function of ubiquitin?

A
  • carboxyl group forms an isopeptide bond w/ multiple lysine residues
  • formed by 3 enzymes
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19
Q

what are the 3 enzymes in ubiquitin?

A
  • E1- ubiquitin activating enzyme
  • E2- ubiquitin conjugating enzyme
  • E3- ubiquitin protein ligase
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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
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21
Q

what 4 functions is a lysosome part of?

A
  • macroautophagy
  • microautophagy
  • chaperone- mediated autophagy
  • phagocytosis
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22
Q

which molecule is the primary mode of protein breakdown- proteasome or lysosome?

A

proteasome

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23
Q

what is the function of the glucose- alanine cycle?

A

to transport nitrogen from amino acid breakdown to the liver (via alanine)

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24
Q

what is corresponding alpha- ketoacid to alanine?

A

pyruvate

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25
Q

what does alanine recycle?

A

carbon backbone and amino group containing nitrogen

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26
Q

what does alanine form along with alpha-ketoglutarate via alanine aminotransferase in the hepatocyte?

A

pyruvate and glutamate- glutamate broken down to urea to excrete the nitrogen

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27
Q

what are xenobiotics?

A

foreign substances that are not produced in the body that have no nutritional value- need to be excreted

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28
Q

what must a substance be in order to be excreted?

A

water soluble

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29
Q

what is a phase 1 biotransformation reaction?

A
  • non synthetic
  • adds or exposes functional groups (-OH, -SH, -NH2, -COOH)
  • small increase in hydrophilicity
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30
Q

what are the 3 main types of phase 1 reactions?

A
  • oxidation
  • reduction
  • hydrolysis
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31
Q

what are the main phase 1 oxidation reactions?

A
  • hydroxylation
  • N- and O- dealkylation
  • deamination
  • epoxidation
  • oxygen addition
  • hydrogen removal
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32
Q

what are the main phase 1 reduction reactions?

A
  • hydrogen addition
  • oxygen removal
  • donor molecules for these reactions include GSH, FAD, NAD(P)H
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33
Q

what are the main phase 1 hydrolysis reactions?

A

splitting of amide (C-N-C) and ester (C-O-C) bonds

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34
Q

what is a phase II biotransformation reaction?

A
  • biosynthetic
  • conjugation with endogenous molecules
  • e.g. glucoronic acid, sulphate, glutathione
  • covalent bonds formed
  • large increase in hydrophilicity
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35
Q

what are examples of phase II reactions?

A
  • glucuronidation (glycoside conjugation)
  • sulphation
  • methylation
  • acylation (acetylation, amino acid conjugation, deacetylation)
  • phosphate conjugation
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36
Q

what types of reaction of transferase enzymes mainly responsible for?

A

phase II reactions

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37
Q

where are cytochrome P450 enzymes found and what are they responsible for?

A
  • smooth ER

- phase I reactions

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38
Q

where are microsomal enzymes present?

A

smooth ER of liver, kidneys, lungs and intestinal mucosa

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39
Q

what reactions are microsomal enzymes responsible for?

A
  • drug biotransformation reactions

- oxidative, reductive, hydrolytic and glucuronidation

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40
Q

where are non microsomal enzymes found?

A

cytoplasm and mitochondria of hepatocytes and other tissues

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41
Q

what reactions are non microsomal enzymes responsible for?

A

non- specific enzymes that catalyse few oxidative, reductive and conjugation reactions

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42
Q

why is ethanol not metabolised via phase I and II reactions?

A
  • does not need to be conjugated for excretion

- only up to 10% os excreted- rest is used in liver as a dietary fuel

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43
Q

which enzyme catalyses the metabolism of ethanol?

A

alcohol dehydrogenase (ADH)

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44
Q

what is the other pathway by which ethanol can be metabolised?

A

microsomal ethanol oxidising system

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45
Q

how does ethanol cause liver damage?

A
  • alcohol abuse= accumulation of acetaldehyde
  • toxic
  • forms adducts with amino acids- causes alcohol induced hepatitis
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46
Q

what does oxidation of acetaldehyde produce?

A

acetate and NADH + H+

47
Q

what is paracetamol also known as?

A

acetaminophen

48
Q

how is acetaminophen safely metabolised?

A

via glucuronidation or sulphation

49
Q

how can overdosing on acetaminophen cause liver damage?

A
  • 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
Q

what are the main functions of bile?

A
  • lipid digestion and absorption
  • cholesterol homeostasis
  • excretion of lipid soluble xenobiotics, drug metabolites and heavy metals
51
Q

how much bile is produced per day?

A

500-600mls/ day

52
Q

what is enterohepatic circulation?

A
  • 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
Q

what happens during the fasting stage of enterohepatic circulation?

A

bile acids acids travel down biliary tract to gall bladder

54
Q

what happens during the fed stage of enterohepatic circulation?

A
  • 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
Q

how are bile acids reabsorbed in the enterohepatic circulation?

A

via apical sodium bile acid transporter (ASBT) in the ileum

56
Q

how many cycles of enterohepatic circulation occur during a meal?

A

2-3 cycles

57
Q

what happens in the interdigestive stage of enterohepatic circulation?

A

sphincter of Oddi contracts and gall bladder relaxes- encourages secreted bile to enter the gall bladder

58
Q

what are bile acids synthesised from?

A

cholesterol

59
Q

what are the 2 main primary bile acids synthesised from cholesterol?

A
  • cholic acid

- chenodeoxycholic acid

60
Q

what does conjugation do to bile acids?

A

makes them more hydrophilic and acidic

61
Q

what are the functions of bile acids?

A
  • 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
Q

why does emulsification occur?

A
  • triglycerides insoluble in water

- increases surface area for lipolysis

63
Q

what does amphipathic mean?

A
  • having both hydrophobic and hydrophilic parts

- reduces surface tension and aids emulsification

64
Q

which enzyme acts on bilirubin in the hepatocyte to form bilirubin diglucoronide?

A
  • UDP glucoronyl transferase
  • acts twice- each time adding glucoronic acid
  • forms conjugated bilirubin
65
Q

what forms stercobilinogen from conjugated bilirubin?

A

intestinal bacteria

66
Q

by what pathway does stercobilinogen form stercobilin?

A

oxidation

67
Q

what compound gives faces its brown colour?

A

stercobilin

68
Q

what is urobilinogen formed from?

A

stercobilinogen

69
Q

how is urobilin formed?

A

oxidation of urobilinogen in the kidneys

70
Q

what gives urine its yellow colour?

A

urobilin

71
Q

what organelle produces pancreatic enzymes?

A

rough ER

72
Q

why are granules secreted by acinar cells?

A

as precursors to protect the pancreas

73
Q

what is the mechanism for secretion of pancreatic enzymes?

A
  • 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
Q

what is the control mechanism of pancreatic enzyme secretion?

A
  • presence if fatty acids and amino acids in small intestine
  • increased CCK secretion
  • increased enzyme secretion
75
Q

what inhibits pancreatic enzyme secretion?

A

somatostatin

76
Q

what causes the movement of water into the pancreatic lumen?

A

movement of Na+ and HCO3- into lumen forms an osmotic pressure gradient- therefore promoting the movement of water

77
Q

how is bicarbonate secretion controlled?

A
  • low pH in small intestine
  • increased secretin excretion
  • increased HCO3- secretion
78
Q

what inhibits bicarbonate secretion?

A

somatostatin

79
Q

what are the 3 phases of pancreatic secretion?

A
  • cephalic
  • gastric
  • intestinal
80
Q

what happens during the cephalic phase?

A
  • 20-25% of secretion

- stimulation for cholinergic vagal input

81
Q

what happens during the gastric phase?

A
  • 10% secretion

- vago-vagal reflex stimulate by gastric distention

82
Q

what happens during the intestinal phase?

A
  • 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
Q

what cells secrete CCK?

A

I cells

84
Q

where is iron absorbed?

A

duodenum

85
Q

how is iron lost?

A
  • desquamation (loss of skin cells)

- menstruation

86
Q

what is the structure of ferritin?

A
  • 24 covalently linked subunits

- subunits form a shell around a central core containing up to 5000 iron atoms

87
Q

where is ferritin found?

A
  • mostly in cytoplasm of cells

- some found in serum

88
Q

what is the relationship between concentration of ferritin and total iron stores in the body?

A

proportional

89
Q

what are the daily requirements of vitamin A?

A
  • Male- 0.6mg/day

- Female- 0.7mg/day

90
Q

what are the functions of vitamin A?

A
  • vision- forms rhodopsin
  • reproduction- formation of spermatogenesis and prevention of foetal resorption
  • growth
  • stabilise cell membranes
91
Q

what are the functions of vitamin D?

A
  • increase intestinal absorption of Ca2+
  • resorption and formation of bone
  • reduce renal excretion of Ca2+
92
Q

what are the daily requirements of vitamin E?

A
  • Male- 4mg/ day

- Female- 3mg/ day

93
Q

what is the function of vitamin D?

A

antioxidant

94
Q

what are the functions of vitamin K?

A
  • activation of blood clotting factors

- synthesis of clotting factors II, VII, IX, X

95
Q

what vitamins are fat soluble?

A

ADEK

96
Q

what vitamins are water soluble?

A

C, B12, folate

97
Q

what are the functions of vitamin C?

A
  • collagen synthesis
  • antioxidant
  • iron absorption
98
Q

what are the 2 forms of vitamin B12?

A
  • methylcobalamin

- 5- deoxyadenosylcobalamin

99
Q

how is vitamin B12 released from food and absorbed?

A
  • 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
Q

what is the function of folate?

A
  • coenzyme in methylation reactions
  • DNA synthesis
  • synthesis of methionine from homocysteine
101
Q

how is the intrinsic clotting pathway activated?

A

contact

102
Q

how is the extrinsic clotting pathway activated?

A

by FVII coming in contact w/ tissue factor

103
Q

which clotting factors are produced by the liver?

A

I (fibrinogen), II (prothrombin), IV, V, VI, VII

104
Q

how is the performance of the extrinsic pathway measured?

A

prothrombin time

105
Q

how is the performance of the intrinsic pathway measured?

A

activated partial thromboplastin time (aPTT)

106
Q

where does the liver develop?

A

ventral mesentery

107
Q

where does the spleen develop?

A

dorsal mesentery

108
Q

what are the liver and endo & exocrine pancreas developed from?

A

endoderm

109
Q

what is the connective tissue of the pancreas and liver derived from?

A

visceral mesoderm

110
Q

where in the foregut do the liver and 2 pancreatic buds develop from?

A

duodenum

111
Q

what attaches the liver to the anterior abdominal wall?

A

falciform ligament

112
Q

what does the dorsal pancreatic bud form?

A

head, neck, body and tail

113
Q

what does the ventral pancreatic bud form?

A

uncinate process

114
Q

why are the superior mesentery artery and vein located infront of the uncinate process?

A

ventral pancreatic bud loops behind them during development before fusing with the dorsal pancreatic bud

Nicks phase 1 flashcards (16 decks)

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