lecture 17/18

Question 1

CFTR activation pathway

Answer 1

-Cystic Fibrosis Transport conductance Regulator
-GPCR/G protein/adenylyl cyclase/cAMP/Protein kinase phosphorylates R domain/ATP binds to Nucleotide Binding Domain/hydrolysis energy opens channel

Question 2

Oral rehydration therapy

Answer 2

-Sodium Chloride and glucose to stimulate water uptake into cells

-pump of sodium across membrane attracts Cl- and H2O through paracellular transport so isotonic fluid movement

-used to treat secretory diarrhea (cholera) but not osmolarity induced diarrhea

Question 3

Cystic fibrosis lung pathology

Answer 3

-CFTR gene mutation so disfunction or missing
- Cl- can’t move out of cell.
-Hypotonic, water moves into cell
-dry surface, thick sticky mucus, cant breathe

Question 4

kidneys tight junctions effect

Answer 4

tight junctions tighter/more selective at distal end to reabsorb NaCl (more transcellular transport)
tight junctions less strands/more permeable at proximal end to reabsorb most filtrate -bulk movement water/glucose (more paracellular transport)

Question 5

facilitated diffusion

Answer 5

-carrier or channel transport protein
-no atp
-solute moves down conc. gradient

Question 6

treatment for glucose/galactose malabsorption

Answer 6

-glucose can’t pass through SGLT protein
-fructose diet replaces glucose
-fructose can diffuse across apical membrane of cell via GLUT 5, diffuse across basal-lateral membrane via GLUT 2

Question 7

diabetes glucosuria

Answer 7

-plasma glucose levels above renal threshold 200 mg/100mL
-maximum glucose transport on left y axis = 375 mg/min
-right y axis amount of glucose in urine
-SGLT saturation so glucose not absorbed and found in urine

Question 8

secretion

Answer 8

entry: basal-lateral membrane has Na/K pump establish gradient, glucose diffuse into cell from blood with Na
exit: apical membrane, glucose diffuse out, may need active transport to enter another cell

Question 9

absorption

Answer 9

entry: apical membrane has Na/K pump establish gradient, has glucose/Na symporter bringing glucose into cell
exit: basal-lateral membrane, glucose diffuses out

Question 10

GIT/kidneys proximal

Answer 10

-duodenum in the small intestine
-proximal tubule in the kidneys
-lots of paracellular transport
-90% of transport

Question 11

GIT/kidneys distal

Answer 11

-colon in GIT
-collecting duct in kidneys
-lots of transcellular transport
-10% of transport

Question 12

cystic fibrosis vs cholera in chloride secretion

Answer 12

cystic fibrosis: cystic fibrosis transport conductance regulator (CFTR) disfunction so Cl- can’t move out of cell (lung surface dehydrates)

cholera: enterotoxin skips receptor, irreversibly binds to adenylyl cyclase so CFTR effectively always open. Cl- out of cell attracts Na+ and H2O so excessive fluid loss from cells.

Question 13

sweat formation secretory coil pathways

Answer 13

parasympathetic (rest, digest) - acetylcholine activates IP3, Ca2+ path. Ca2+ binds to calcium gated chloride channel

sympathetic (fight/flight) - noradrenaline activates cAMP production/ kinase A phosphorylates R domain of chloride channel

both isotonic fluid secretion

Question 14

why does Cl- move into cell in reabsorptive duct of sweat formation

Answer 14

membrane is depolarised from -80 to -60 millivolts so Cl- can move down conc. gradient

Question 15

cystic fibrosis sweat formation

Answer 15

-CFTR mutated/broken so no sweat forms by sympathetic pathway, only via parasympathetic calcium gated chloride channel
-no reabsorption as only CFTR in this duct so salty sweat

Question 16

signs of cystic fibrosis

Answer 16

-super salty sweat
-defects of epithelia cells

Question 17

organs affected by cystic fibrosis

Answer 17

pancreas, liver, GIT, airways, reproductive tract, skin

Question 18

obstruction by cystic fibrosis affects which organs?

Answer 18

Pancreas - enzymes can’t be delivered for digestion
Airways - clogging of bronchioles impedes breathing, most CF patients die from lung disease
Liver - blocking of bile ducts impedes digestion, can prevent liver function
Female reproductive - occasionally mucus plug blocks sperm from uterus
Small intestine/large intestine - colon blocked

Question 19

glucose/galactose malabsorption cause

Answer 19

sodium-glucose linked transporter mutation prevents glucose from entering cell –> higher osmolarity in small intestine lumen –> excessive water diffusion into lumen causing diarrhea

Question 20

chloride secretion mechanism

Answer 20

gradient set up by:
1.) primary active transport - 3Na+/2K+ pump

2.) 2Cl-/Na+/K+ symporter so high conc of Cl- in cell

3.) Cl- can only leave cell if CFTR activated, Na+ leaves cell either via pump or channel

4.) movement of Cl- induces water and Na+ movement into lumen

Question 21

secretory diarrhea mechanism

Answer 21

overstimulation of CFTR either by secretagogues from inflammation or tumours (reversible binding) or more commonly cholera enderotoxins (irreversible)

Question 22

secretory diarrhea location of oversecretion

Answer 22

in crypt cells of small intestine or colon

secretion overwhelms the absorptive capacity of colon causing secretory diarrhea

Question 23

cystic fibrosis overview

Answer 23

autosomal (affecting any non sex 22 chromosomes) recessive disorder

heterozygotes have no symptoms but there are carriers

affects children and young adults (older die median age survival 38)