Intestines physio Flashcards
major ions secreted in small intestine
- Cl-
- HCO3-
Na+ (less important)
where are the ions secreted in small intestine
- crypt
how does Cl- secretion occur & lead to water secretion
apical membrane:
- Cl- secreted by intestinal cell through CFTR (cystic fibrosis transmembrane conductance regulator) into intestinal lumen
- -ve charge brings Na+ & water into intestinal lumen as well (via PARACELLULAR route)
how does intestinal cell maintain [Cl-] despite constant Cl- secretion
basolateral membrane:
- contains Na+, K+, ATPase -> pumps out 3Na+ for 2K+ -> causes Na+ deficit within cell
- contains NKCC1 (Na K Cl cotransporter) -> pumps K, Na, 2Cl into intestinal cell with help to [Na+] gradient (created by NaKATPase) -> [Cl-] is maintained
how does HCO3- secretion occur in intestinal cell (2)
same as other GIT cells
- presence of DRA (downregulated in adenoma) -> secrete HCO3- in exchange for Cl-
- presence of CFTR -> pump both Cl- and HCO3- out of intestinal cell
how does intestinal cell maintain [HCO3-] within cell (2)
- carbonic anhydrase -> convert CO2 to H2CO3 -> dissociate, HCO3- is produced, H+ is removed from cell via NHE (Na H exchanger) on basolateral membrane
basolateral membrane:
- presence of NBC1 (Na HCO3 cotransporter) -> cotransports Na and HCO3- into intestinal cell
what do the intestines secrete
intestinal juice
- water, electrolytes, mucous
- mucus & electrolytes secreted by crypts (driven by Cl- secretion through CFTR)
what stimulates production of intestinal juice (4)
- mechanical irritation of mucosa
- distenstion of gut
- ACh (vagal) , PG, guanylin
- 2nd messengers - cAMP, cGMP, Ca
functions of intestinal fluid
- maintain fluidity of chyme
- alkalinise contents for enzymatic activity
major ions secreted in COLON
- K+ (distal)
- Cl-
- HCO3-
what does the colon secrete
- mucus
- intestinal fluid (pH8-8.4), contains high K+ & HCO3- -> buffers against H+ produced by bacterial fermentation in colon
what stimulates colonic secretion (2)
- parasympathetic nerve impulses
- mechanical/ chemical irritation of mucosa
how do DISTAL colonic cells secrete K+ (ability is NOT present in intestinal cells)
- Na+ enters cell via apical membrane from lumen (process can be upregulated by aldosterone)
- increase in Na+ within cell creates electrochemical potential -> allows K+ to be secreted at apical membrane via K+ channels -> into lumen
2 routes for intestinal absorption
- transcellular -> electrolytes, nutrients; higher transepithelial resistance (2 membranes involved) and usually active processes are needed
- paracellular -> lower resistance & molecules flow through tight junctions (junctions are looser at duodenum and become tighter [less permeable] down the GI tract)
substances that are reabsorbed at small intestines (6)
- water
- nutrients (glucose, amino acids)
- Na+ (thus H2O)
- CO2
- Cl-
- K+
how does water reabsorption occur in small intestines & what is an effect of water reabsorption
- coupled to solute movement -> absorption of water is controlled by amount of electrolyte & nutrients (mainly glucose, Na+) absorbed
*water usually moves PARACELLULARLY
effect:
- solvent drag phenomenon -> eg K+ will be reabsorbed along with water
how are nutrients absorbed into small intestines
TRANSCELLULAR
secondary active transport
- presence of NaKATPase at apical membrane pumps Na+ out of cell -> create Na gradient from lumen
- SGLT: Na-glucose cotransporter allow absorption of glucose with Na+ into cell
how is Na+ reabsorbed in small intestine (2)
TRANSCELLULAR
- Na-glucose cotransporter
- Na-H antiport on apical membrane -> absorb Na+ in exchange for H+ secretion
how is HCO3-/CO2 reabsorbed into small intestine
TRANSCELLULAR
- Na-H antiport secretes H+ into lumen -> H+ combines with HCO3- in lumen to form CO2 -> diffuse back into cell and into blood
how is Cl-reabsorbed in small intestine
- through PARACELLULAR junction
how is K+ reabsorbed in small intestine
PARACELLULAR
- moves via solvent drag -> dragged along with water paracellularly as it is dissolved in water
substances that are reabsorbed at large intestine/ colon
PROXIMAL COLON
mainly
- H2O
- electrolytes (Na, Cl)
some
- CO2
DISTAL COLON
mainly
- Na+
**K+ secretion
how are electrolytes absorbed at PROXIMAL colon
TRANSCELLULAR
- electroneutral NaCl absorption -> absorbs Na along with Cl
how is water absorbed at PROXIMAL colon
coupled to solute movement
- Na+ and Cl- generate osmotic gradient -> water reabsorbed PARACELLULARLY
how is CO2 absorbed at PROXIMAL colon (same as small intestine)
TRANSCELLULAR
- Na-H antiport secretes H+ into lumen -> combine with HCO3- to form CO2 -> diffuses though cell back into blood
how is Na+ reabsorbed at DISTAL COLON
- Na+ moves into distal colon via electrogenic sodium pump (controlled by aldosterone)
- allows secretion of K+ afterwards by creating electrochemical gradient
how is iron absorbed in small intestine (2)
HEME
- absorbed by heme transporter -> broken down to Fe2+ in enterocyte
Fe3+
- reduced to Fe2+ by ferric reductase -> absorbed by DMT1
what happens to Fe2+ in enterocytes (2)
- converted to Fe3+ and stored in enterocyte as Fe3+-ferritin
- transported through ferroportin into blood
how is iron absorption regulated (high iron stores -> less absorption; vice versa)
HEPCIDIN
- reduces ferroportin activity
- high iron stores -> liver increases hepcidin production -> reduce ferroportin & iron movement into blood
- Fe3+ - ferritin stores build up in enterocyte (iron is trapped in enterocyte) -> enterocyte eventually gets shed -> Fe stores disappear
how is Vitamin B12 (cobalamine, CBL) absorbed in small intestines?
- CBL is initially bound to proteins in food -> pepsin in stomach releases CBL -> CBL binds to haptocorrin (secreted by gastric glands, protects CBL from degradation)
- gastric parietal cells secrete IF (intrinsic factor) which follows CBL-haptocorrin into small intestine
- pancreas secrete protease into small intestine -> degradation of haptocorrin -> IF-CBL complex forms
- IF-CBL absorbed at ILEAL enterocytes -> endocytosis and degradation to release CBL
how are carbohydrates digested in small intestines (2)
- LUMINAL salivary & pancreatic amylase
- MUCOSAL disaccharidases (on brush borders of enterocytes)
products of luminal digestion by amylase in small intestine
- maltotriose (3x glucose)
- maltose
- a-limit dextrins (contain a-1,6 linkages, cannot be broken down by amylase
what are the mucosal disaccharidases present on brush border of enterocytes (3) + their functions
sucrase-isomaltase (2 enzymes attached tgt)
- isomaltase splits a-limit dextrins, maltose, maltotriose
- sucrase splits sucrose, maltose, maltotriose
lactase
- splits lactose
glucoamylase
- splits maltotriose, maltose
how are glucose and galactose molecules transported across apical membrane
SGLT
- sodium linked glucose transporter (secondary ACTIVE transport) -> cotransport glucose/ galatose with help of Na+ concentration gradient
GLUT5
- glucose transporter (facilitated transport/ passive diffusion) -> transport fructose down concentration gradient (maintained as fructose is rapidly metabolised into glucose & lactic acid upon entering cell)
how do the sugars absorbed from intestinal lumen enter the blood?
GLUT 2
- on basolateral membrane of enterocyte -> transport glucose/ fructose/ galactose into blood via FACILITATED DIFFUSION (concentration of sugars are much higher within enterocyte)
how are proteins digested in small intestines (3)
- LUMINAL gastric pepsin (from stomach), pancreatic protease
- MUCOSAL enterocyte peptidases (found brush border of enterocytes)
- INTRACEULLAR peptidases
how are proteins absorbed by small intestines
- gastric & pancreatic peptidases + mucosal enterocyte peptidases -> breaks down proteins into 1) tripeptides 2) dipeptides 3) amino acids
tripeptides & dipeptides:
- absorbed via H+ cotransporter (PEPT1)
amino acids:
- absorbed via Na+ cotransporter
what happens to tripeptides & dipeptides inside enterocytes
- digested to form amino acids
*amino acids are then transported out through basolateral membrane by Na+-independent AA transporters (at least 3 distinct transporters present for diff AA groups)
how are dipeptides/ tripeptides absorbed into the cell
- NHE secretes H+ into intestinal lumen in exchange for Na+
- H+ is coupled with di-, tri peptides and absorbed into cell via PEPT1 (peptide transporter 1)
are di-, tripeptides OR amino acids more easily absorbed at apical membrane?
- di-, tripeptides as PEPT1 more efficient
how are whole proteins absorbed
- endocytosis of proteins by enterocyte/ M cells
- some are degraded while others exit basolateral membrane as whole proteins
what is emulsification
- breaking down of fat globule into fat/ emulsion droplets
characteristic of bile that helps with emulsification
- amphipathic -> can surround fat droplets while hydrophilic sites face out and hydrophobic sites face inwardds
what causes intragastric digestion of fats (2)
- gastric lipases (20-30%) -> intragastric lipolysis
- lingual lipases (from saliva)
what causes luminal digestion of fats
- emulsification
- lipolysis by gastric lipase (pH4.5-6, majority inactive in stomach); PANCREATIC lipase (pH>7)
*pancreatic lipase is enhanced by colipase
types of pancreatic lipase
- glycerol ester hydrolase (MAIN)
- cholesterol esterase
- phospholipase A2
how is glycerol ester hydrolase activated
- binds to colipase to form complex -> has better access to lipids in emulsion & micelle + exposes active site of lipase to substrate + target fat water interface
*bile acids wrap around fat droplet and prevents glycerol ester hydrolase from breaking fat down -> colipase opens up the bile acid covering
what are fat droplets broken down into by lipase?
micelle
- extremely hydrophobic materials (eg cholesterol) are stored within interior of micelle
- requires minimum amount of bile salts to be formed
how are micelles absorbed
- diffusion through unstirred water layer (possible as bile salts are hydrophilic) -> RATE LIMITING STEP
- micelle reaches enterocyte and lipid content is rapidly removed once contacted with microvilli
what proportion of lipids are absorbed
- almost all (>95% for triglycerides) -> fat in stools is from colonic bacteria & desquamated intestinal cells
where are bile salts reabsorbed
terminal ileum (receptor mediated process)
where are SCFA (short chain fatty acids) found, eg acetate, propionate, butyrate
- not dietary
- synthesized by bacteria -> PRIMARY nutrient for colonic epithelial cells
what does absorption of SCFA by colon stimulate?
- Na & water absorption at colon (SCFA is water soluble)
absorption of medium chain fatty acids (C6-12)
- more water soluble thus micelle formation is unnecessary
- esters are absorbed directly (hydrolysis not needed)
- MFCA are more efficiently absorbed
- NO NEED re esterification and chylomicron formation for absorption
- exits via portal blood (unlike long chain fatty acid, too long to enter blood)
absorption of long chain fatty acids (LCFA)
- post-absorptive handling (re-esterification)
- drains into lymphatic duct, thoracic duct then systemic circulation
why is post-absorptive handling required for long chain fatty acids
LCFA cannot dissolve in blood -> needs to be re esterified and drained via lymphatics
process of post-absorptive handling
occurs in epithelial cell of small intestine
- fatty acid components (cholesterol, mono glyceride, fatty acids) are re-esterified into cholesterol esters/ phospholipids/ triglyceride -> grouped together to form CHYLOMICRON
- chylomicron is exocytosed into extravascular space -> drains into lymph node -> thoracic duct -> systemic circulation
what are the nutrients absorbed at different parts of the small intestine
Proximal small intestine
- fat, sugar, peptides & amino acids, iron, folate, Ca, water and electrolytes
Middle small intestine
- sugar, peptides & amino acids, Ca, water and electrolytes
Distal small intestine
- bile salts, Vit B2, water & electrolytes
Colon
- water & electrolytes
tissue permeability of small intestine & large intestines to water
Jejunum:
- leaky (HIGHH fluid reabsorption)
Ileum:
- moderately leaky (HIGHH fluid reabsorption)
Cecum
- moderately tight (LOW fluid reabsorption)
Colon
- tight (HIGH fluid reabsorption, although no where as high as jejunum/ ileum)
potential difference of small intestines & large intestine
jejunum < ileum < cecum < colon
- tighter epithelial cells -> greater potential difference when ions are reabsorbed
absorptive mechanisms of water in small intestines & large intestines
Jejunum:
- Na-nutrient
- Na-H+
Ileum:
- Na-Cl
- Na-nutrient
- Na-bile acid
Cecum:
- Na+
- SCFA
Colon:
- Na-Cl
- SCFA
reasons for diarrhea (4)
HYPERMOTILITY of intestine (inflammation)
- less absorption time
HYPEROSMOLARITY
- unabsorbed nutrients (eg vit B12 malabsorption, excess lactose in lactose intolerance)
- osmotic, malabsorption
LOSS OF ABSORPTIVE CAPACITY
- loss of villi, loss of length (eg resection)
- malabsorption
ENHANCED SECRETION OF WATER & ELECTROLYTES
- secretory diarrhoea
- bacterial toxins – cholera, E. coli, Clostridium difficile
- tumours – VIP, carcinoid
