Physiology of the intestine Flashcards
What are the two phases of amino acid absorption in the small intestine?
- Cleavage of peptides to amino acids by brush border dipeptidases
- Carrier-mediated Na+ coupled transport (specific for each AA) across apical cell membrane
What are the two steps for glucose and galactose absorption across the apical SI cell membrane? How is fructose different?
- hydrolysis of CHO by disaccharidases
- secondary active transport of glucose or galactose along with Na+ into enterocyte
Fructose absorbed by facilitated diffusion
How are triglycerides in the lumen absorbed by the enterocytes? ( 6 steps)
- Emulsified into micelles by bile salts
- Pancreatic lipase hydrolyses them to monoglycerides and FFAs
- Carried in the micelle to the brush border
- Leave the micelle and diffuse across the apical cell membrane
- Resynthesised to triglycerides within the cell, aggregate and are coated with lipoprotein to form chylomicrons (water soluble)
- Chylomicrons extruded from basolateral surface by exocytosis and enter lymphatic lacteals
How is Na+ absorbed from the intestinal lumen?
Passive diffusion down electrochemical gradient
Secondary active transport with glucose or amino acids via ATPase-set concentration gradient
Is the large or small intestine more efficient at water absorption?
Large
Which hormone plays a role in regulating water absorption in the large intestine and how?
Aldosterone - upregulated Na/K ATPase on basolateral membrane of colonic mucosal cells to promote passive Na absorption
What do paneth cells secrete and where are they located? Which species have them?
Ruminants and horses ONLY
Peptidase and lysozyme
Located in the crypts of Lieberkuhn in the small intestine
What are the crypt (3) and villus (2) cell types of the small intestine?
Crypt cells - chloride secreting columnar cells - paneth cells - stem cells Villus cells - columnar absorptive cells - goblet cells
Which segment of small intestine has shortest villi?
The duodenum.
Which segment of the small intestine has the greatest density of goblet cells?
The jejunum and ileum
What do Brunner’s gland secrete? Where are they?
Submucosa of the duodenum only
Secrete mucous in dogs and ruminants
or mucoserous in cats and horses
or serous secretion in pigs
Which two pathogens may promote Cl- secretion by the crypt columnar cell CFTR channel and how?
Cholera - increases intracellular cAMP
E.coli variant - increases intracellular cGMP
What sort of tonicity would an oral rehydration therapeutic have?
ISOTONIC - don’t want to pull fluid out of the tissues with a hypertonic solution
How does oral rehydration therapy work?
Assumes the SGLT transporter is unaffected by the toxin - give glucose load to lumen to increase SGLT activity, Na+ absorption and water by osmosis
What is the other name for coabalamin? How is it absorbed?
Vitamin B12
Must bind to intrisic factor secreted by gastric parietal cells or pancreas
Sudden onset of profuse watery diarrhoea -
where is the problem most likely to be?
Small intestine as responsible for majority of water reabsorption and greatest Cl- secretion
Large volume of pale, soft faeces could be due to..?
Liver or biliary dysfunction e.g inefficient enterohepatic circulation or bile duct obstruction
Soft, mucoid faeces of increased frequency most likely due to?
Inflammation of the colon due to increased water and mucous content
What are the six major defences of the GIT mucosa?
- Mucous layer and glycocalyx
- Mucosal lymphoid system
- High cell turnover
- Differential ion permeability and secretion
- Good blood supply
- Tight junctions between cells
What are three protective functions of the glycocalyx layer?
- Reduces shearing forces on the epithelial surface
- helps to bind and aggregate bacteria, preventing their colonisation
- Impairs absorption of some water soluble molecules
Where is the inner glycocalyx layer thickest? Does it usually contain bacteria?
The stomach; and no is usually sterile
The glycocalyx contains mucins, immunoglobulins and antimicrobials. What are two cells that contribute to these secretions?
Paneth cells
Goblet cells
What is the difference between secreted and cell membrane bound mucins?
Secreted = heavily glycosylated glycoproteins that bind bacteria
Cell membrane = transmembrane proteins with cytoplasmic domains that participate in cell signalling, long and filamentous extracellular domain may bind bacteria - can cause cell shedding into lumen
If bacteria do not bind the mucin, what is another way they may be repelled from the mucosa?
Steric hindrance - repelled by negative charge of mucin
What are the three major strategies for pathogens to avoid the mucous layer, and what is an example of each?
- Penetrate mucous layer e.g through motility (flagella)
- Avoid the mucous layer e.g enter via M cell, which has no covering
- Alteration to host barrier e.g secretion of toxins that damage tight junctions or inhibit mucous production
What are three factors that might modulate mucous secretion in the GIT?
Hormones e.g prostaglandins
Cholinergic stimulation
Microbial population
What is the function of M cells?
Present commensal microbial antigen to underlying immune cells
Which leukocyte predominates in the Peyer’s patches?
B cells
What is the lifespan of an enterocyte?
Stomach and SI = 3 - 4 days
- Same for goblet cells
LI = 5 - 7 days
What is the lifespan of a parietal cell?
100 days
Why are parietal cells more resistant to H+ damage than others?
They are less permeable to H+
Other than PGE2, what are two other molecules that may stimulate crypt stem cell proliferation in the GIT?
TGF alpha
Epidermal growth factor
Also increase mucous and decrease acid secretion
What three major things must be considered when anticipating the absorption of a drug via the GIT?
- The absorptive capacity of the epithelium
- inflammation may increase drug absorption
- villous atrophy or glandular metaplasia may decrease - Drug concentration and dilution
- diluted by food
- concentration gradient across mucosa may be altered by increased or decreased motility - Solubility of drug
- may be influenced by pH of lumen contents
- water soluble drugs may move readily with bulk flow
What else might affect the bioavailability of an oral drug?
Bind to food
Digested by enzymes
Not absorbed due to no bile acid secretion so not emulsified
Lost to first pass metabolism
What sort of virus is Parvovirus? What aspects of the mucosal defence does it breach?
Radiomimetic = targets rapidly dividing cells leading to destruction of crypt stem cells and sometime lymphoid tissue
- Atrophy of villi
- Erosion of mucosa
