Lecture 22 - Alimentary 3

Question 1

Briefly explain the mechanism of cell turnover in crypts:

Answer 1

Enterocytes are produced in crypts (proliferate zone). They then migrate to the surface where they are sloughed into the lumen. Crypt cells are secretory whereas the villous cells are absorptive

Question 2

Is turnover of enterocytes slower or faster in neonates or in older animals?

Answer 2

Turnover of enterocytes is slower in neonates than older animals

Question 3

Below is a diagram showing carbohydrate digestion and absorption fill in the missing molecules and transporters:

Answer 3

1. glucose
2. fructose
3. SGLT1
4. GLUT5
5. GLUT2

Question 4

What are the three different ways that proteins can be digested and absorbed?

Answer 4

1. Luminal enzymes digest proteins to peptides and then amino acids which are absorbed
2. Lumen enzymes digest proteins to peptides, bursh border peptidases digest these to amino acids which are then absorbed
3. Luminal enzymes digest proteins to oligopeptides (di and tripeptides) which are taken up by enterocytes - cytosolic peptidase hydrolysis produces amino acids that are then trasnported across the basolateral membrane

Question 5

How are lipids digested and absorbed?

Answer 5

1. Pancreatic lipase breaks lipids down into monoglycerides and free fatty acids
2. Then enter into the cell and re-absorbed and re-assembled as triglycerides or long and short chain fatty acids are absorbed directly
3. They are then formed in chylomicrons and are hen absorbed across the surface

Question 6

How is sodium absorbed in the large intestine?

Answer 6

nutrient coupled Na+ transport via the SGLT1 on apical and Na+/K+ on the basolateral surface. The Cl- is then transported passively via the paracellular pathway in response to the lumen-negative transepithelial potential difference.

Question 7

How is sodium re-absorbed in the small intestine and the colon?

Answer 7

In the small intestine and the colon extracellular Na+ is exchanged for intracellular H+ via the NHE3. Driven by electrochemical gradient driven by Na+/K+ - ATPase exchanger. Na-H exchange enhanced by decreased intracellular pH and increased luminal pH.

Question 8

How is the NHE3 transporter inhibited?

Answer 8

inhibited by cAMP and cGMP (+ the diuretic amiloride)

Question 9

Breifly explain how electroneutral Na+ and Cl- absorption occurs in the ileum and proximal colon:

Answer 9

1. In the ileum and the proximal colon - Na+ absorption is coupled to movement of Cl- through Cl- - HCO3- anion exchanger
2. HCO3- produced by intracellular metabolism and from intracellular CO2
3. The tight coupling with NH3 results in electroneutral Na+ and Cl- absorption and maintenance of cell pH and luminal release of H+ and HCO3-
4. Overall electroneutral NaCl absorption is decreased by increases in cAMP

Question 10

How does electrogenic sodium absorption occur in the distal colon?

Answer 10

1. Drive by Na+ specific aldosterone sensitive ion channel
2. Driven by downhill electrochemical Na+/K+ - ATPase pump
3. Cl- absorbed passively via paracellular pathway in response to lumen-negative transepithelial potential difference generated by movement of other ions

Question 11

How and from what cell does chloride secretion occur in the small intestine? and what is the purpose of it?

Answer 11

In both the small and large intestine - Cl- secreted from crypt cells. Cl- provides the main driving force for fludi secretion into the lumen. In small intestine it is also the main source of luminal Cl- for Cl- - HCO3- anion exchanger. The secretion is regulated by second messengers cAMP, cGMP and Ca2+. It is stimulated by secretagogues (susbtances promoting secretion) causes opening of pre-exisiting and insertion of new Cl- channels - associated with secretory diarrhoea.

Question 12

What are the main short chain fatty acids that are generated in the small and in the large intestine?

Answer 12

Small intestine: main anions are Cl- and HCO3-

Colon: main anions are SCFA’s (acetate, propionate and butyrate)

Question 13

How are short chain fatty acids generated and what is the how do they prevent diarrohoea?

Answer 13

Rapid absorption in the colon enhances Na+ and fluid re-absorption.

SCFA’s upregulate NHE3 expression on colonocyte apical membrane. At colonic pH, 95% of SCFAs are ionised but need to be in non-ionised form to diffuse into colonocytes. The apical NHE3 exchanger creates an acidic pH, enhancing diffusion of non-ionised SCFAs into cells

Question 14

Order the following into net absorption and net secretion in the small intestine:

water, sodium (active), potassium (passive), chloride (in exchange for bicarbonate), non-electrolytes such as glucose, amino acids, lipids and bile salts, bicarbonate

Answer 14

Net absorption: water, sodium (active), potassium (passive), chloride (in exchange for bicarbonate), non-electrolytes such as glucose, amino acids, lipids and bile salts

Net secretion: bicarbonate (in exchange for chloride)

Question 15

Divide the following into net absroption and secretion in the large intestine:

Water, sodium, chloride, SCFA’s, potassium, bicarbonate

Answer 15

Net absorption: water, sodium, chloride, SCFA’s

Net secretion: potassium, bicarbonate

NOTE: non-electrolytes such as glucose, amino acids, lipids and bile salts cannot be absorbed in the large intestine - they are fermented

Question 16

How much water is absorbed daily in animals, where from and by what mechanism?

Answer 16

The total volume that is absorbed daily is about 10% of body weight, it normally occurs passively. Majority of this occurs in mucosa of the upper small intestine .

Question 17

What are the four main mechanisms of diarrhoea? Provide a potential cause of each one:

Answer 17

1. Maldigestion/malabsorption (malassimiliation) - caused by ingestion of poorly absorbed solutes and diseases causing loss of mucosal surface area (villous atrophy)
2. Secretion - bacterial toxins, inflammatory mediators, endogenous laxatives
3. Changes in intestinal permeability - acute inflammation (enteroinvasive bacteria) and chronic inflammation
4. Changes in intestinal motility

Question 18

What is the mechanism of action of osmotic diarrhoea?

Answer 18

1. Increased amounts of solute (mainly ions and organic molecules) raise effect osmotic pressure of intestinal contents)
2. Water in drawn into intestinal lumen down the osmotic gradient

Question 19

How do saline laxatatives such as magnesium sulphate (Epsom salts) and sodium sulphate result in maldigestion/malabsorption (=Malassimilation)?

Answer 19

These are poorly absorbed from the intestinal tract causing excess water to move into intestinal lumen.

Question 20

How does the feeding of poorly digestible milk replacer lead to maldigestion/malabsorption (=malassimilation)?

Answer 20

Maldigested material reaches large intestine, then undergoes fermentation increasing the osmotic drag of water.

Question 21

Explain the effect of the villus atrophy that is shown below on GIT function and provide an examples of a disease that could cause this:

Answer 21

Malsassimilation - loss of intestinal surface markedly reduces the digestive and absorptive capacity.

Potential disease - TGE, rotavirus, parvovirus

Question 22

Briefly explain the compensatory ability of the large intestine in preventing diarrhoea:

Answer 22

Colon has considerable reserve capacity. The XS sugars are converted to SCFA (=VFA) which are then rapidly absorbed.

Question 23

What are the two main ways the large intestine can contribute to dirrhoea?

Answer 23

1. Colon without well-developed flora (e.g. neonate) means that the XS sugars are not converted to SCFA and hence draw XS water into lumen. This results in the production of osmotic diarrhoea
2. Colon has well-develoepd flora, but it is overloaded with readily fermentable carbohydrate. The pH falls as lactic acid is produced resulting in the production of osmotic diarrhoea

Question 24

What is secretory diarrhoea and when might it be expected?

Answer 24

Result of increased active ion trasnport mechanisms, especially chloride, in both the small intestine and the colon. Would be expected if no demostratable biochemical lesions is present.

Question 25

What is the mechanism of secretory diarrhoea?

Answer 25

1. The toxin acts the epithelial cells
2. Causes the ADP-ribosylation of Gs alpha subunit of G-protein
3. Permanently activates and keeps activating adenylate cyclase
4. Overproduction of cyclic adenosine monophosphate (cAMP)
5. Increased secretion of chloride into the lumen
6. Inhibits the channels that let sodium and chloride into the cell
7. Increased levels of luminal sodium and chloride disrupt osmotic balance between intestines and surrounding tissues
8. Draws water, bicarbonate and potassium into the lumen

Question 26

What is the pathogen that is responsible for the appearance shown below?

Answer 26

Enterotoxigenic Escherichia coli (noninvasive)

Question 27

What is the mechanism of action enterotoxigenic Escherichia coli?

Answer 27

Question 28

Compare the intestinal fluid losses of secretory versus malabsorbative diarrhoea:

Answer 28

Secretory dirrhoea = hgih volume

Malabsorbative = low-volume

Question 29

What are some examples or acute and chronic enteroinvasive bacterial diseases and how do they cause diarrhoea?

Answer 29

Acute enteroinvasive bacterial diseases = Salmonella and some E.colis

Chronic enteric diseases = Johnes disease (ruminants), eosinophillic enteritis (horses) and histiocytic coltis (dogs)

They result in movement of electrolytes and protein into lumen. This creates a osmotic gradient luminal movement of water - producing diarrhoea

Question 30

What is the name of the condition that is shown below and what are the complications that are commonly seen with it?

Answer 30

Acute Salmonellosis (Enteroinvasive)

Fever, watery diarrhoea, dehydration, endotoxic shock, hyponatremia, hypokalaemia, hypochloremia, hypoalbuminaemia, metabolic acidosis

Question 31

What is the name of the condition that is shown below, what is the likely bacterial agent causing it, what are the clinical signs, how does it cause diarrhoea?

Answer 31

Chronic inflammation: Johne’s disease caused by mycobacterium avium ssp. paratuberculosis

Clinical signs: chronic diarrhoea, emaciation and hypoproteinaemia

Question 32

For image below:

1. Name the condition
2. State the pathologic effects
3. Provide a likely clinical sign that would be seen

Answer 32

1. Eosinophillic enteritis in horses
2. Thickened gut wall due to infiltration with eosinophils and infiltration of mesenteric lymph nodes - variable eosinophilic granuloma formation in mucosa
3. Protein loosing enteropathy

Question 33

Name the condition that is shown below:

Answer 33

Histiocytic ulcerative colitis

Question 34

What is a potential side effect of reduced gastro-intestinal motility?

Answer 34

Small intestine - reduced moltility may predispose to bacterial overgrowth (that can then lead to malabsorption)