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JL Gastrointestinal > Water Balance in the GI tract > Flashcards

Water Balance in the GI tract Flashcards

1
Q

What is a passive process driven by the transport of solutes (particularly Na+) from the lumen of the intestines to the bloodstream?

A

Absorption of water

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2
Q

How much water enters the tract per day?

A

9.3 litres

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3
Q

How much water is absorbed by the small intestine?

A

8.3 litres

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4
Q

How much water enters the large intestine, and of that what percentage is absorbed?

A

1 litre, 90% absorbed

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5
Q

What has 100ml in faeces and what has 50ml, along with, bilirubin and bacteria?

A

100ml water

50ml cellulose

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6
Q

What is defined as a loss of fluid and solutes from the GI tract in excess of 500ml per day?

A

Diarrhoea

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7
Q

What is intestinal fluid movement always coupled to?

A

Solute movement

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8
Q

What two ways may water move?

A

Transcellular

Paracellular

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9
Q

What two prinicple mechanisms of Na absorption occurs throughout the small intestine and is most omportant in the post-prandial period (also occurs in the colon in the new born)?

A

Na+/glucose co-transport

Na+/amino-acid co-transport

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10
Q

What prinicple mechanism of Na movement occurs in the duodenum and jejunum and is stimulated by HCO3?

A

Na+/H+ exchange

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11
Q

Where does Na+/H+ exchange occur?

A

In duodenum and jejunum

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12
Q

What stimulates Na+/H+ exchange?

A

HCO3

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13
Q

Where and at what time does the parallel Na+/H+ and Cl-/HCO3 exchange occur?

A

In the ileum and colon, most important in the interdigestive period

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14
Q

What principle mechanism for Na exchange occurs in the colon (distal) and is regulated by aldosterone?

A

Epithelial Na+ channels (ENaC)

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15
Q

What to mechanisms of postprandial Na+ absorption are examples of secondary active transport and are electrogenic?

A

Na+/glucose and Na+/amino acid co-transport

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16
Q

Collectively, what does the overall transport of Na+ generate?

A

A transpepithelial potential (Vte) in which the lumen is negative

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17
Q

Due to the transepithelial potential in which the lumen is negative, what does this drive?

A

Parallel absorption of Cl-

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18
Q

Where does Na+/H+ exchange in the jejunum occur at?

A

Both the apical and baseolateral membranes (via different isoforms of the exchanger)

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19
Q

During Na+/H+ exchange in the jejunum, what two things contribute to transepithelial movement of Na+ and the regulation of intracellular pH?

A

NHE2 and NHE3

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20
Q

What is exchange at the apical membrane, in the jejunum stimulated by?

A

The alkaline environment of the lumen due to presence of bicarbonate from the pancreas

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21
Q

In the jejunum, what is absent?

A

A parallel Cl–HCO3 exchanger

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22
Q

What is the primary mechanism of Na+ absorption in the interdigestive period?

A

Na+/H+ and Cl-/HCO3- exchange in parallel

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23
Q

In Na+/H+ and Cl-/HCO3-, what is absorption like?

A

Electroneutral

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24
Q

In Na+/H+ and Cl-/HCO3-, what is it regulated by?

A

Intracellular cAMP, cGMP and Ca2+, all of which reduce NaCl absorption

25
Q

What is reduction in NaCl absorption a cause of?

26
Q

Explain how secretory diarrhoea is caused due to infection with E. coli?

A

Enterotoxin from which activates adenylate cyclase and increases intracellular cAMP, reducing NaCl absorption

27
Q

What mediates electrogenic Na+ absorption in the distal colon?

A

Epithelial Na+ channels (ENaC)

28
Q

What is ENaC increased by?

A

Aldosterone

29
Q

What are the three actions of aldosterone on ENaC?

A
  1. opens ENaC
  2. Inserts more ENaC into membrane from intracellular vesicle pool
  3. Increases synthesis of ENaC and Na+/K+-ATPase
30
Q

What two routes can Cl absorption occur passively on?

A

Transcellular and paracellular

31
Q

In the small intestine, what is the driving force for Cl- absorption provided by?

A

Lumen negative potential due to electrogenic transport of Na+ in Na+/glucose and Na+/amino-acid co-transporty]

32
Q

In the large intestine, what is the driving force provided by for the absorption of Cl-?

A

Lumen negative potential due to electrogenic movement of Na+ through ENaC.

33
Q

What is another mechanism for Cl- absorption that occurs in the ileum, proximal and distal colon?

A

Cl-HCO3- exchange

34
Q

What is another mechanism for Cl- absorption that occurs in the ileum and proximal colon?

A

parallel Na+/H+ and Cl-/HCO3 exchange

35
Q

What occurs at a basal rate but is usually overshadowed by a higher rate of absorption?

A

Cl- secretion

36
Q

What cells does Cl- secretion occur from?

A

Crypt cells

37
Q

What membrane does Cl- absorption into cell before secretion occur at?

A

Basolateral

38
Q

What are the three processes involed on the basolateral membrane in Cl- secretion?

A
  1. Na+/K+ATPase
  2. Na+/K+/2Cl-co-transporter (NKCC1)
  3. K+ channels (IK1 and BK)
39
Q

In Cl- secretion, what does low intracellular Na+ drive?

A

Inward movement of Na+, K+ and Cl- via NKCC1

40
Q

In Cl- secretion, once low intracellular Na+ drives inward movement of Na+, K+ and Cl- via NKCC1, what occurs next?

A

K+ recycles via K+ channels, but intracellular concentration of Cl- increases providing an electrical chemical gradient for Cl- to exit cell via CFTR on teh apical membrane.

41
Q

In Cl- secretion, once Cl- has exited the cell via CFTR on the apical membrane, what happens?

A

Lumen negative potential develops providing voltage-dependent secretion of Na+ through paracellular pathway

42
Q

What has to be active for Cl- secretion to occur?

43
Q

What 4 substances activate CFTR?

A
  1. bacterial enterotoxins
  2. Hormones and neurotransmitters
  3. Immune cells products
  4. Some laxatives
44
Q

Activation of CFTR also occurs indirectly as a result of the generation of what three second messengers?

A
  1. cAMP
  2. cGMP
  3. Ca2+
45
Q

What two things does the Cl- conductance mediated by CFTR result from?

A
  1. Opening of channels at the apical membrane

2. Insertion of channels from intracellular vesicles into the membrane

46
Q

What causes metabolic acidosis, due to loss of HCO3 and hypokalaemia?

47
Q

What 4 factors can lead to impaired absorption of NaCl and so lead to dairrhoea?

A
  1. Congenital defects - congenital chloridorrhoea absence of Cl–HCO3 exchanger
  2. Inflammation
  3. Infection
  4. Excess bile acid in colon
48
Q

What is a cause of non-absorbable solutes in intestinal lumen - leading to diarrhoea?

A

Lactase deficiency

49
Q

What provides a classic example of excessive secretion to lead to diarrhoea?

50
Q

Once cholera toxin has entered the enterocyte, what does it enzymatically inhibit?

A

GTPase activity of the Gsalpha subunit.

51
Q

What does enzymatically inhibited GTPase increase the activity of?

A

Adenylate cyclase leading to increased cAMP

52
Q

What does cAMP stimulate and what does it lead to?

A

CFTR - hypersecretion of Cl- with Na+ and water following

53
Q

What does this describe: 2Na+ binds to SGLT1, affinity for glucose increases so glucose binds, Na+ and glucose translocate from extracellular to intracellular, 2Na+ dissociates, affinity for glucose falls so glucose dissociates and the cycle repeats?

A

Rehydration therapy exploting SGLT1

54
Q

What types of drugs have anti-diarrhoeal activity/

A

Morphine and opiate drugs

55
Q

What do opiates do to enteric neurones?

A

Inhibit them causing hyperpolarisation via activation of u-opoid receptors

56
Q

What do opiates do to peristalsis and segmentation?

A

Decreased peristalsis and increased segmentation (i.e. constipating)

57
Q

What do opiates do to fluid absorptin?

A

Increase it

58
Q

What drugs cause constriction of pyloric, ileocaecal and anal sphincters?

59
Q

Name three major opiates used in diarrhoea?

A

Codeine
Diphenoxylate
Loperamide

JL Gastrointestinal (33 decks)

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