Physiology of the intestine

Question 1

What are the two phases of amino acid absorption in the small intestine?

Answer 1

1. Cleavage of peptides to amino acids by brush border dipeptidases
2. Carrier-mediated Na+ coupled transport (specific for each AA) across apical cell membrane

Question 2

What are the two steps for glucose and galactose absorption across the apical SI cell membrane? How is fructose different?

Answer 2

1. hydrolysis of CHO by disaccharidases
2. secondary active transport of glucose or galactose along with Na+ into enterocyte

Fructose absorbed by facilitated diffusion

Question 3

How are triglycerides in the lumen absorbed by the enterocytes? ( 6 steps)

Answer 3

1. Emulsified into micelles by bile salts
2. Pancreatic lipase hydrolyses them to monoglycerides and FFAs
3. Carried in the micelle to the brush border
4. Leave the micelle and diffuse across the apical cell membrane
5. Resynthesised to triglycerides within the cell, aggregate and are coated with lipoprotein to form chylomicrons (water soluble)
6. Chylomicrons extruded from basolateral surface by exocytosis and enter lymphatic lacteals

Question 4

How is Na+ absorbed from the intestinal lumen?

Answer 4

Passive diffusion down electrochemical gradient

Secondary active transport with glucose or amino acids via ATPase-set concentration gradient

Question 5

Is the large or small intestine more efficient at water absorption?

Answer 5

Large

Question 6

Which hormone plays a role in regulating water absorption in the large intestine and how?

Answer 6

Aldosterone - upregulated Na/K ATPase on basolateral membrane of colonic mucosal cells to promote passive Na absorption

Question 7

What do paneth cells secrete and where are they located? Which species have them?

Answer 7

Ruminants and horses ONLY

Peptidase and lysozyme

Located in the crypts of Lieberkuhn in the small intestine

Question 8

What are the crypt (3) and villus (2) cell types of the small intestine?

Answer 8

Crypt cells
- chloride secreting columnar cells 
- paneth cells
- stem cells
Villus cells
- columnar absorptive cells
- goblet cells

Question 9

Which segment of small intestine has shortest villi?

Answer 9

The duodenum.

Question 10

Which segment of the small intestine has the greatest density of goblet cells?

Answer 10

The jejunum and ileum

Question 11

What do Brunner’s gland secrete? Where are they?

Answer 11

Submucosa of the duodenum only

Secrete mucous in dogs and ruminants

or mucoserous in cats and horses

or serous secretion in pigs

Question 12

Which two pathogens may promote Cl- secretion by the crypt columnar cell CFTR channel and how?

Answer 12

Cholera - increases intracellular cAMP

E.coli variant - increases intracellular cGMP

Question 13

What sort of tonicity would an oral rehydration therapeutic have?

Answer 13

ISOTONIC - don’t want to pull fluid out of the tissues with a hypertonic solution

Question 14

How does oral rehydration therapy work?

Answer 14

Assumes the SGLT transporter is unaffected by the toxin - give glucose load to lumen to increase SGLT activity, Na+ absorption and water by osmosis

Question 15

What is the other name for coabalamin? How is it absorbed?

Answer 15

Vitamin B12

Must bind to intrisic factor secreted by gastric parietal cells or pancreas

Question 16

Sudden onset of profuse watery diarrhoea -

where is the problem most likely to be?

Answer 16

Small intestine as responsible for majority of water reabsorption and greatest Cl- secretion

Question 17

Large volume of pale, soft faeces could be due to..?

Answer 17

Liver or biliary dysfunction e.g inefficient enterohepatic circulation or bile duct obstruction

Question 18

Soft, mucoid faeces of increased frequency most likely due to?

Answer 18

Inflammation of the colon due to increased water and mucous content

Question 19

What are the six major defences of the GIT mucosa?

Answer 19

1. Mucous layer and glycocalyx
2. Mucosal lymphoid system
3. High cell turnover
4. Differential ion permeability and secretion
5. Good blood supply
6. Tight junctions between cells

Question 20

What are three protective functions of the glycocalyx layer?

Answer 20

1. Reduces shearing forces on the epithelial surface
2. helps to bind and aggregate bacteria, preventing their colonisation
3. Impairs absorption of some water soluble molecules

Question 21

Where is the inner glycocalyx layer thickest? Does it usually contain bacteria?

Answer 21

The stomach; and no is usually sterile

Question 22

The glycocalyx contains mucins, immunoglobulins and antimicrobials. What are two cells that contribute to these secretions?

Answer 22

Paneth cells

Goblet cells

Question 23

What is the difference between secreted and cell membrane bound mucins?

Answer 23

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

Question 24

If bacteria do not bind the mucin, what is another way they may be repelled from the mucosa?

Answer 24

Steric hindrance - repelled by negative charge of mucin

Question 25

What are the three major strategies for pathogens to avoid the mucous layer, and what is an example of each?

Answer 25

1. Penetrate mucous layer e.g through motility (flagella) 2. Avoid the mucous layer e.g enter via M cell, which has no covering 3. Alteration to host barrier e.g secretion of toxins that damage tight junctions or inhibit mucous production

Question 26

What are three factors that might modulate mucous secretion in the GIT?

Answer 26

Hormones e.g prostaglandins Cholinergic stimulation Microbial population

Question 27

What is the function of M cells?

Answer 27

Present commensal microbial antigen to underlying immune cells

Question 28

Which leukocyte predominates in the Peyer's patches?

Answer 28

B cells

Question 29

What is the lifespan of an enterocyte?

Answer 29

Stomach and SI = 3 - 4 days - Same for goblet cells LI = 5 - 7 days

Question 30

What is the lifespan of a parietal cell?

Answer 30

100 days

Question 31

Why are parietal cells more resistant to H+ damage than others?

Answer 31

They are less permeable to H+

Question 32

Other than PGE2, what are two other molecules that may stimulate crypt stem cell proliferation in the GIT?

Answer 32

TGF alpha Epidermal growth factor Also increase mucous and decrease acid secretion

Question 33

What three major things must be considered when anticipating the absorption of a drug via the GIT?

Answer 33

1. The absorptive capacity of the epithelium - inflammation may increase drug absorption - villous atrophy or glandular metaplasia may decrease 2. Drug concentration and dilution - diluted by food - concentration gradient across mucosa may be altered by increased or decreased motility 3. Solubility of drug - may be influenced by pH of lumen contents - water soluble drugs may move readily with bulk flow

Question 34

What else might affect the bioavailability of an oral drug?

Answer 34

Bind to food Digested by enzymes Not absorbed due to no bile acid secretion so not emulsified Lost to first pass metabolism

Question 35

What sort of virus is Parvovirus? What aspects of the mucosal defence does it breach?

Answer 35

Radiomimetic = targets rapidly dividing cells leading to destruction of crypt stem cells and sometime lymphoid tissue - Atrophy of villi - Erosion of mucosa