Physiology of Fluid & Electrolyte Movement

Question 1

What process is the absorption of water & what drives it?

Answer 1

Passive process, driven by the transport of solutes (particularly Na+) from the lumen of the intestines to the bloodstream

Question 2

Water that is ingested & secreted is normally in balance with what?

Answer 2

Water absorption

Question 3

What are the typical values of water absorption in the body?

Answer 3

8.3 litre absorbed by small intestine
1 litre enters large intestine of which 90% is absorbed

Question 4

How many litres of water enter the tract per day?

Answer 4

9.3 litre

Question 5

What do the faeces contain?

Answer 5

100ml water along with 50ml cellulose, bilirubin, & bacteria

Question 6

What is diarrhoea defined as?

Answer 6

Loss of fluid & solutes from the GI tract in excess of 500ml per day

Question 7

What is absorption of water in the GI tract largely driven by?

Answer 7

absorption of Na+

Question 8

What is intestinal fluid movement always coupled to?

Answer 8

Solute movement

Question 9

What are the 2 routes in which water can move via?

Answer 9

Transcellular or paracellular

Question 10

What does absorption of sodium provide?

Answer 10

A (local) osmotic force for reabsorption of water

Question 11

Where does Na+/glucose co-transport & Na+/amino acid co-transport occur?

Answer 11

Occurs throughout the small intestine and is most important in the postprandial period (also occurs in the colon in the new born)

Question 12

Where does Na+/H+ exchange occur?

Answer 12

Occurs in the duodenum and jejunum and is stimulated by luminal HCO3

Question 13

Where does parallel Na+/H+ & Cl-/HCO-3 exchange occur?

Answer 13

Occurs in the ileum and colon most important in the interdigestive period (does not contribute to postpandrial absorption)

Question 14

Where does epithelial Na+ channels (ENaC) occur?

Answer 14

Occurs in the colon (distal particularly) and is regulated by aldosterone

Question 15

What kind of transport is the Na+/glucose and Na+/amino acid cotransport?

Answer 15

Secondary transport & are electrogenic, so is the Na+/K+ ATPase

Question 16

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

Answer 16

Transepithelial potential (VTE) in which the lumen is negative - this drives the parallel absorption of Cl-

Question 17

What are the Na+/glucose & Na+/amino acid cotransport not regulated by?

Answer 17

Intracellular cAMP, or calcium

Question 18

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

Answer 18

occurs at both the apical (NHE2 and NHE3) and basolateral (NHE1) membranes, but only NHE2 (not shown) and NHE3 contribute to transepithelial movement of Na+ (and the regulation of intracellular pH).

Question 19

What is NHE1?

Answer 19

Cellular pH housekeeper

Question 20

what is Na+/H+ exchange at the apical membrane stimulated by?

Answer 20

The alkaline environment of the lumen (ie high pH= low proton concentration) due to the presence of bicarbonate from the pancreas.

Question 21

What kind of absorption is parallel Na+/H+ & Cl-/HCO-3?

Answer 21

Electroneutral

Question 22

How is parallel Na+/H+ & Cl-/HCO-3 regulated?

Answer 22

By intracellular cAMP, cGMP and Ca2+ - all reduce NaCl absorption

Question 23

What does reduction in NaCl absorption cause?

Answer 23

Diarrhoea - (e.g. secretory diarrhoea due to infection with E. coli – heat stable enterotoxin from which activates adenylate cyclase and increases intracellular cAMP)

Question 24

What does epithelial Na+ channels (ENaC) mediate?

Answer 24

Electrogenic Na+ absorption in the distal colon

Question 25

What is epithelial Na+ channel (ENaC) important in?

Answer 25

Highly efficient & important in Na+ conservation

Question 26

What increases epithelial Na+ channel (ENaC) & what is it not regulated by?

Answer 26

Increases by aldosterone but not regulated by cAMP or cGMP

Question 27

What are the three actions of aldosterone?

Answer 27

(i) opens ENaC (seconds); (ii) inserts more ENaC into membrane from intracellular vesicle pool (minutes) and (iii) increases synthesis of ENaC and Na+/K+-ATPase (hours)

Question 28

What routes can Cl- absorption occur?

Answer 28

Can occur passively via transcellular or paracellular routes

Question 29

In the small intestine, what causes the driving force provided by lumen negative potential?

Answer 29

Electrogenic transport of Na+ (Na+/glucose & Na+/amino acid)

Question 30

In the large intestine, what causes the driving force provided by lumen negative potential?

Answer 30

electrogenic movement of Na+ through ENaC

Question 31

What are the other mechanisms of Cl- absorption

Answer 31

(i) Cl- - HCO3- exchange (ileum, proximal and distal colon) and (ii) parallel Na+ - H+ and Cl- - HCO3- exchange (ileum and proximal colon)

Question 32

At what rate does Cl- secretion occur?

Answer 32

Occurs at a basal rate, but is usually overshadowed by a higher rate of absorption

Question 33

What does Cl- secretion occur from?

Answer 33

Crypt cells, rather than villus cells

Question 34

What is Cl- secretion important in?

Answer 34

In many diarrhoeas

Question 35

What are the three processes involved on the basolateral membrane?

Answer 35

Na+/K+ATPase Na+/K+/2Cl- co-transporter (NKCC1) K+ channels (IK1 and BK)

Question 36

What does low intracellular Na+ drive?

Answer 36

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

Question 37

What does K+ recycle via?

Answer 37

K+ channels

Question 38

What happens to the concentration of intracellular Cl-

Answer 38

Cl- increases providing an electrochemical gradient for Cl- to exit cell via CFTR on the apical membrane

Question 39

What does the developing lumen negative potential provide?

Answer 39

voltage-dependent secretion of Na+ through paracellular pathway

Question 40

Normally, why is there little secretion of Cl-?

Answer 40

Occurs because apical CFTR is either closed, or not present

Question 41

When does secretion of Cl- occur?

Answer 41

when CFTR is indirectly activated by: * bacterial enterotoxins * several hormones and neurotransmitters * immune cells products * some laxatives (e.g. bile acids)

Question 42

What results in the activation of CFTR directly?

Answer 42

the generation of second messengers in response to: * bacterial enterotoxins * several hormones and neurotransmitters * immune cells products * some laxatives (e.g. bile acids) includes: * cAMP * cGMP * Ca2+

Question 43

What results in the Cl- conductance mediated by CFTR?

Answer 43

* opening of channels at the apical membrane * insertion of channels from intracellular vesicles into the membrane

Question 44

What is the overall effect of the role of CFTR?

Answer 44

Secretory diarrhoea

Question 45

What causes diarrhoea?

Answer 45

infectious agents – viruses, bacteria (e.g. traveller’s diarrhoea) chronic disease toxins drugs psychological factors

Question 46

What is involved in diarrhoea?

Answer 46

Small intestine or large intestine

Question 47

What can diarrhoea result in?

Answer 47

dehydration (Na+ and H2O loss), metabolic acidosis (HCO3- loss) and hypokalaemia (K+ loss) My be fatal if severe eg cholera

Question 48

What are the treatments for severe acute diarrhoea?

Answer 48

maintenance of fluid and electrolyte balance (first priority) use of anti-infective agents (if appropriate) use of non-antimicrobial antidiarrhoeal agents (symptomatic)

Question 49

What causes impaired absorption of NaCl?

Answer 49

congenital defects (e.g. congenital chloridorrhoea – absence of Cl- - HCO3- exchanger) inflammation excess bile acid in colon

Question 50

What causes non-absorbable, or poorly absorbable, solutes in intestinal lumen?

Answer 50

Lactase deficiency