PHYS - Gut Secretions Flashcards
1
Q
what are the salivary (buccal) glands?
A
- extrinsic: parotid, sublingual, submandibular
- also intrinsic (line oral mucosa and secrete saliva directly into the mouth)
2
Q
factors which influence salivation
A
- sleep (decreased salivation)
- acidic foods (increased salivation)
- approach and presence of food
- nausea (increased salivation to make mouth alkaline to prepare for acidic vomit)
- fear (decreased salivation)
3
Q
composition of saliva
A
- majority water
- ions (e.g. Ca3PO4 helps prevent demineralisation of teeth)
- salivary amylase (ptyalin) - starch > sugar
- mucin (lubrication)
- Ig to prevent microbial colonisation in mouth
4
Q
functions of saliva
A
- lubrication (mucin)
- digestion (salivary amylase/ptyalin)
- protection (Ig and Ca3PO4)
- control of H2O intake (thirst reflex)
- speech (movement of tongue is helped by saliva)
- absorption (sublingual)
- taste sensation
5
Q
pharmacological Tx for increased/decreased salivation
A
- to treat ptyalism (increased salivation): muscarinic (M3) antagonist e.g. LOW DOSE atropine (so we don’t get systemic effects)
- to treat xerostomia (decreased salivation): muscarinic (M3) agonist e.g. pilocarpine
6
Q
test for xerostomia
A
- xerostomia = dry mouth due to not enough saliva
- ‘dry cracker test’ - give dry cracker with no water and see if they have difficulty swallowing
7
Q
functions of stomach
A
- storage area
- mechanical digestion and propulsion
- initiation of protein digestion via pepsin
- intrinsic factor to help with absorption of Vit B12 for RBC maturation > deficiency in intrinsic factor causes pernicious anaemia
- absorption of some fat soluble substances
8
Q
what are gastric glands
A
- located under gastric pits (invaginations of simple columnar epithelium)
- contain 4 types of secretory cells: mucous cells, parietal cells, chief cells, enteroendocrine cells
9
Q
function of 4 gastric secretory cells
A
- mucous cells: secrete mucus
- parietal cells: secrete HCl and intrinsic factor
- chief cells: secrete pepsinogen (inactive form of pepsin)
- enteroendocrine: (enterochromaffin-like cells produce histamine, G cells produce gastrin)
10
Q
how is pepsinogen activated to become pepsin
A
- optimal pH = 2
- chief cells secrete pepsinogen
- parietal cells secrete HCl (brings pH down to 2) and intrinsic factor
- pepsinogen activated into pepsin
11
Q
why do we need a low stomach pH
A
- activation of pepsinogen has an optimum pH of 2
- kills ingested bacteria
- breaks down cellulose
12
Q
gastric acid TRIGGER pathway
A
- vagus n. releases ACh - binds to M3 receptors on parietal cells
- vagus n. also stimulates G cells > release gastrin > causes ECL cells to release histamine
- histamine binds to H2 receptors on parietal cells
- parietal cell produces HCl
13
Q
what is somatostatin?
A
- inhibits gastrin, histamine and parietal cells
14
Q
how do parietal cells secrete HCl?
A
- 3 receptor trigger pathway
- water split into H+/OH-
- H+ actively pumped into lumen via H+/K+ ATPase pump
- OH- combines with CO2 to form HCO3- which is exchanged for Cl- on basolateral membrane and passively leaves parietal cell via Cl- channels
- this is called alkaline tide b/c HCO3- mops up free H+ in blood which increases pH (temporary metabolic alkalosis)
- H+ and Cl- combine in lumen to make HCl
15
Q
2 types of drugs for excess gastric acid secretion
A
- antihistamine: inhibits H receptors on basolateral surface (less effective b/c there is still the G and M pathways)
- proton pump inhibitor (PPI) = inhibit H+/K+ pump on luminal membrane of parietal cell (most effective b/c blocks common pathway)
16
Q
phases of increased gastric acid secretion following a meal
A
- 1) cephalic phase: sensory approach or presence of food causes activation of vagus n. = increased HCl secretion
- 2) gastric phase: swallowed food enters stomach = distension, rising pH and semi-digested proteins = increased HCl secretion
- 3) intestinal phase: chyme enters into duodenum = distension, acidic pH and protein digestion products = INHIBITION of vagus n. and secretion of enterogastrones (gut hormones): secretin, gastric inhibitory peptide = DECREASED HCl secretion
17
Q
bile secretion pathway
A
- liver produces bile out of many ducts (intrahepatic biliary tree)
- converge into bile canaliculi > ductules > R and L hepatic ducts > common hepatic duct
- between meals, cystic duct takes bile and stores it in gallbladder
- cystic duct and common hepatic duct join to form common bile duct
- CBD merges with pancreatic duct to empty bile into duodenum
18
Q
composition and functions of bile components
A
- cholesterol: precursor of bile salts
- bile salts and lecithin (phospholipid): combine
to emulsify fats in small intestine along with contractions - electrolytes and water: bicarbonate neutralises acidic chyme in duodenum
- bile pigments (biliverdin): produced by breakdown of haem from haemoglobin or myoglobin
19
Q
how is bile formed and modified
A
- bile salts, cholesterol, phospholipids, cholesterol, bilirubin conjugates etc. actively transported across basolateral membrane (into hepatocyte) then apical membrane (into bile canaliculi) and apical membrane
- this creates a concentration gradient > water follows
- cholangiocytes (in bile duct) dilute and alkalinise bile (via bicarbonate), while also absorbing glucose, bile acids and amino acids = helps regulate volume and composition of bile for digestion
20
Q
how are bile acids synthesised
A
- made in hepatocytes from cholesterol and conjugated with glycine/taurine to form bile SALTS
- role in cholesterol homeostasis
- 2 most common: cholic acid and chenodeoxycholic acid
21
Q
process of lipid digestion
A
- bile salts and lecithin emulsify fats into smaller droplets (micelles) along with duodenal contractions (increased SA for digestive enzymes)
- co-lipase helps pancreatic lipase gain access to triglycerides by pushing aside bile salts and lecithin
- TAGs broken down into fatty acids and glycerol > absorbed into bloodstream
22
Q
what triggers bile secretion?
A
- acidity: duodenum secretes secretin (‘nature’s antacid’) = triggers release of bicarbonate from bile ductal cells
- fats: duodenum secretes cholecystokinin (CCK) = causes gallbladder contraction and relaxes Oddi
23
Q
functions of cholecystokinin (CCK)
A
- gallbladder contraction = release of bile
- relaxation of Oddi = allows bile to be emptied into duodenum
- causes pancreas to secrete lipase and colipase
- inhibits stomach churning to enable fat digestion to occur faster (it happens slowly)
- constricts pyloric sphincter to inhibit emptying into duodenum
24
Q
why does the pancreas secrete an alkaline fluid and which cells secrete this?
A
- secreted by ductal cells
- triggered by secretin
- activation of pancreatic enzymes
- protects intestinal mucosa from excess acid
- enables fat emulsification
25
which cells synthesise and secrete pancreatic enzymes?
- zymogen granules synthesise
- acinar cells secrete
26
which enzymes are secreted by the pancreas?
- INACTIVE (b/c otherwise they would break down the pancreas - autodigestion) precursors of trypsin, chymotrypsin, carboxypeptidase, elastase - all break down proteins
- ACTIVE enzymes: lipase, cholesterol esterase, phospholipase, amylase, ribonuclease, deoxyribonuclease
27
function of trypsin, chymotrypsin, elastase
- breaks peptide bonds in proteins to form peptide fragments
28
function of carboxypeptidase and lipase
- splits off terminal amino acid from carboxyl end of protein
- lipase: breaks down triglycerides into two fatty acids + monoglyceride
29
function of amylase, ribonuclease and deoxyribonuclease
- amylase = breaks down polysaccharides into glucose and maltose
- ribo/deoxyribonuclease = breaks down RNA/DNA into free nucleotides
30
how are the inactive enzymes secreted by the pancreas activated?
- triggered by CCK or parasympathetic action
- pancreas secretes trypsinogen > converted to trypsin via membrane-bound enterokinase
- trypsin activates all other inactive enzymes into their active forms
31
what triggers exocrine pancreatic secretions?
- acidity: duodenum secretes secretin ('nature's antacid') = triggers release of alkaline secretion from pancreatic ductal cells
- fats: duodenum secretes cholecystokinin (CCK) = causes enzyme secretion from pancreatic acinar cells to digest proteins, fats and carbs
32
causes of pancreatitis
- inappropriate activation of pancreatic enzymes WITHIN the pancreas = autodigestion (usually caused by excessive alcohol intake or gallstones because they block the CBD leading to pancreas blockage)
- defective ductal secretion of water and HCO3- = lumen is too acidic for enzymes to be activated
- significantly decreased release of pancreatic enzymes (<10%)
33
Sx and Tx of pancreatitis
- Sx: continuous abdominal pain, weight loss (b/c no enzymes to digest and therefore absorb nutrients), steatorrhoea due to fat malabsorption
- Tx: pancreatic supplements to improve nutrition, alcohol abstention, analgesics
34
main pathophys of jaundice
- increased production or reduced excretion of bilirubin
- deposits in tissues due to elastin abundance and rich blood supply e.g. sclera of eye and skin
- usually seen in eyes first b/c non-pigmented
35
synthesis of bilirubin
- breakdown of senescent (old) RBC releases haemoglobin
- haem > biliverdin > bilirubin (unconjugated/indirect - lipid soluble and neurotoxic)
- bilirubin binds to albumin to be transported to liver = conjugated with glucuronic acid > more H2O soluble and non-toxic
- conjugated bilirubin enters bile and forms urobilinogen and then stercobilin (causes brown faeces) in gut or urobilin (in urine)
36
3 classifications of jaundice
- pre-hepatic (haemolytic)
- intra-hepatic
- post-hepatic (obstructive)
37
pre-hepatic (haemolytic) jaundice
- excess haemolysis due to structural defects (e.g. spherocytosis - big and globular instead of flat) or enzyme deficiency (e.g. G6PD deficiency)
- this releases excess haem = excess synthesis of unconjugated bilirubin = increased conjugation of bilirubin (some backflows)
- causes jaundice and pallor (haemolytic anaemia)
- normal colourless urine due to increased urobilinogen in GUT and therefore urine
- normal faeces due to normal conjugated bilirubin in GUT = normal stercobilin
- elevated unconjugated bilirubin in BLOOD b/c liver can't process
38
neonatal jaundice
- mild jaundice is normal b/c they have lots of haemoglobin in the womb
- when born, they need more haemolysis to break this down but liver enzymes are immature so can't conjugate = hepatic jaundice
- also immature BBB so unconjugated bilirubin can deposit in basal ganglia = kernicterus
39
LFT interpretation
- AST and ALT (hepatospecific): these are inside hepatocytes so if hepatocytes are damaged, they will go into blood and be elevated - intrahepatic jaundice
- ALP, GGT (not specific to liver): test for cholestasis (due to obstruction) - posthepatic jaundice
- albumin, clotting factors: check for synthetic function
40
how to determine type of jaundice by LFT
41
intrahepatic jaundice + e.g.s of causes
- less ability for bilirubin conjugation (hepatocyte damage or enzyme deficiency)
- LFT results can be variable depending on pathology i.e. bilirubin may be conjugated or unconjugated
- darker urine due to conjugated bilirubin (causes less urobilinogen)
- normal faeces
- e.g. viral hepatitis, alcohol, non-alcoholic steatosis hepatitis (inflammation caused by fatty liver - NASH)
42
signs of chronic liver disease
- jaundice
- gynaecomastia (due to elevated oestrogen b/c liver responsible for breaking it down)
- spider naevi (dilated arterioles in upper half of chest and arms) - due to vasodilation from excess oestrogen
- palmar erythema - oestrogen
- leukonychia (white nails due to low albumin)
- hepatomegaly and splenomegaly due to backflow of blood
- oedema due to less oncotic pressure in blood
- easy bruising due to less clotting factors
43
post-hepatic (cholestatic) jaundice
- obstruction of bile flow into duodenum = backflow of conjugated bilirubin into biliary tree and BLOOD
- conjugated bilirubin is water soluble so excreted renally = doesn't go thru gut = no urobilinogen or stercobilin = tea-coloured urine and pale stool
44
3 common causes of post-hepatic jaundice
- intra-luminal = gallstones blocking biliary tree
- mural: cholangiocarcinoma, intrahepatic cholestasis (mutliple small blockages within the liver itself e.g. strictures or drug-induced)
- extra-mural = head of pancreas cancer, abdominal masses, pregnancy
45
2 types of gallstones
- excess cholesterol - clumps together to form larger molecules = more difficult to be broken down by bile salts (even tho cholesterol is also broken down into bile salts) = cholesterol precipitates into gallstones
- bilirubin accumulation (e.g. due to liver disease or excess haemolysis) = crystallises and forms stones
