Reabsorption + Secretion

Question 1

What substances are reabsorbed by carrier mediated transport systems?

Answer 1

e.g. glucose, amino acids, organic acids, sulfate and phosphate ions

Question 2

What is T_m? How does it relate to carriers?

Answer 2

Maximum transport capacity

Carrers have a T_m which is due to saturation of carriers; if it is exceeded, then excess substrate enters the urine

Question 3

Capacity is limited by number of carriers; what is ‘renal threshold’?

Answer 3

Plasma threshold (mg/mL) at which saturation occurs

T_m (mg/min), is transport rate at saturation

Question 4

How much of glucose is filtered?

Answer 4

All - it is freely filtered

Question 5

Up to what value will glucose be reabsorbed?

Answer 5

10mmoles/l

Question 6

What happens if concentration of glucose exceeds 10mmoles/l? So what is the distribution of 15mmoles/l plasma {glucose]?

Answer 6

Beyond this level of plasma {glucose}, it appears in the urine = renal plasma threshold for glucose

So 15mmoles/l - 15 filtered, 10 reabsorbed and 5 excreted

Question 7

Does the kidney regulate [glucose]?

Answer 7

NO; insulin and the counter-regulatory hormones are responsible for its regulation

Question 8

What is the normal [glucose]?

Answer 8

5mmoles/l

So T_m is set way above any possible level of (non-diabetic) [glucose], ensuring all this valuable nutrient is normally reabsorbed

Question 9

What does the appearance of glucose in the urine of diabetic patients indicate?

Answer 9

Glycosuria - due to failure of insulin NOT the kidney

Any patient w glucose in urine should be followed up

Question 10

For amino acids, is T_m set high?

Answer 10

YES, set so high that urinary excretion does not occur, as with glucose

(AAs regulated by insulin and counter-regulatory hormones same as glucose)

Question 11

Does the kidney regulate sulfate and phosphate ions?

Answer 11

YES, by means of the T_m mechanism

Question 12

How does the kidney regulate sulfate and phosphate ions by the T_m mechanism?

Answer 12

T_m is set at a level whereby the normal [plasma] causes saturation; so any increase above normal level will be excreted, therefore achieving its plasma regulation

(also subject to PTH regulation for phosphate, PTH decreases reabsorption)

Question 13

Which ions are the most abundant in ECF?

Answer 13

Na+

Question 14

What does this abundance of Na+ ions in ECF mean in terms fo filtration?

Answer 14

A large amount is filtered every day

Question 15

How much Na+ is reabsorbed

Answer 15

180 l/day x 142 mmoles/l = 25560 mmoles/day so 99.5% is reabsorbed

Question 16

How much of Na+ reabsorption occurs in the proximal tubule?

Answer 16

65-75%

Question 17

How are Na+ ions reabsorbed? (NOT by T_m mechanism)

Answer 17

Active transport (establishes a gradient for Na+ across tubule wall)

Question 18

What drives the whole process of Na+ transport?

Answer 18

Na+ pumps

Question 19

Where are active Na+ pumps located? Why?

Answer 19

On the basolateral surface - side which is exposed to the interstitial fluid, not side which is exposed to the tubule lumen, because there is a high density of mitochondria

Question 20

Active Na+ pumps decrease [Na+] in epithelial cells, meaning waht for the gradient of Na+ ions?

Answer 20

Increases the gradient for Na+ ions to move into cells passively across the luminal membrane

Question 21

Na+ is NOT permeable at cell membranes tho, so what about the brush border of the proximal tubule cells has a higher permeability to Na+ ions than most other membranes of the body?

Answer 21

Enormous surface area offered by microvilli and large number of Na+ ion channels, which faciliate this passive diffusion of Na+

Question 22

Reabsorption of Na+ ions is key to what?

Answer 22

Reabsorption of other components of the filtrate

Question 23

How do Cl- ions diffuse across the proximal tubular membrane?

Answer 23

Cl- diffuse across passively down the electrical gradient established and maintained by the active transport of Na+

Question 24

What force does the active transport of Na+ out of the tubule followed by Cl- create? What happens as a result?

Answer 24

Osmotic force

H₂O is drawn out of tubules by osmosis meaning the substances left in the tubule are concentrated creating outgoing concentration gradients

Question 26

What 2 factors does rate of reabsorption of these non-actively reabsorbed solutes depend on?

Answer 26

1. Amount of H₂O removed, which will determine the extent of the concentration gradient 2. The permeability of the membrane to any particular solute

Question 27

How much urea is reabsorbed? Why?

Answer 27

50% Because the tubule membrane is only **moderately permeable** to urea and so remainder stays in the tubule

Question 28

For some substances the tubular membrane is impermeable, name 2; so what happens to them?

Answer 28

Inulin Mannitol Despite conc gradient favouring their reabsorption, they cant gain access through tubule membrane so **all** that is filtered stays in the tubule and passes out in urine

Question 29

It is the active transport of Na+ that establishes the gradients down which other ions, H₂O and solutes pass passively, so anything that decreases active transport e.g. decreased BF, leads to what?

Answer 29

Disruption of renal function

Question 30

How is transport of sodium related to transport of substances such as glucose, amino acids etc?

Answer 30

They share the same carrier molecule as Na+ (symport) High [Na+] in the tubule facilitates and low [Na+] inhibits glucose transport (Na+ reabsorption also linked to HCO₃- ion reabsorption)

Question 31

What is the function of the SGLT (sodium-dependent glucose transporter)?

Answer 31

Allows Na+ to move into the proximal tubule cell down its electrochemical gradient and pulls glucose into the cell against its concentration gradient

Question 32

How are glucose and Na+ diffused out of the proximal tubule cell?

Answer 32

Glucose diffuses out the basolateral side of the cell using the GLUT protein Na+ is pumped out by Na+-K+-ATPase

Question 33

What is tubular secretion?

Answer 33

Secretory mechanisms transport substances **from** the peritubular capillaries **into** the tubule lumen and provide a second route into the tubule

Question 34

What substances is tubular secretion important for? Why?

Answer 34

Substances that are protein-bound, since filtration at glomerulus is very restricted Also for potentially harmful substances, means they can be eliminated more rapidly

Question 35

**T_m -limited carrier-mediated secretory mechanisms** are known for a large number of endogenous as well as exogenous substances such as...

Answer 35

drugs

Question 36

What is the benefit to carrier-mediated secretory mechanisms not beinf very specific?

Answer 36

So that e.g. organic acid mechanism (which secretes lactic and uric acid) can also be used for substances such as penicillin, aspirin and PAH (para-amino-hippuric acid)

Question 37

Similary, organic base mechanism for choline, creatinine etc can be used for what?

Answer 37

Morphine and atropine

Question 38

Where are all of these substances secreted?

Answer 38

Proximal tubule

Question 39

What is the major cation in the cells of the body? (making its balance essential for life)

Answer 39

K+

Question 40

What is normal ECF[K+]

Answer 40

~4mmoles/l

Question 41

What happens in hyperkalaemia ([K+] up to 5.5mmoles/l)?

Answer 41

Decreased resting membrane potential of excitable cells and eventually ventricular fibrillation and death (Nernst equation)

Question 42

What happens in hypokalaemia ([K+] \<3.5mmoles/l)?

Answer 42

Increased resting membrane potential i.e. hyperpolarises muscle, cardiac cells -\> cardiac arrythmias and eventally death

Question 43

Where is K+ filtered at the glomerulus primarily reabsorbed?

Answer 43

Proximal tubule

Question 44

What are changes in K+ *excretion* due to?

Answer 44

Changes in its *secretion* in the distal parts of the tubule

Question 45

Any increase in renal tubule cell [K+] due to increased ingestion will result in...

Answer 45

Increased K+ secretion

Question 46

Any decrease in intracellular [K+] will result in...

Answer 46

reduced secretion

Question 47

In addition, K+ secretion is regulatd by what hormone?

Answer 47

Aldosterone

Question 48

How is aldosterone production stimulated by potassium?

Answer 48

An increase in [K+] in ECF bathing the aldosterone secreting cells stimulates aldosterone release which circulates to the kidneys to stimulate increase in renal tubule cell K+ secretion

Question 49

In addition to regulating potassium, what else does aldosterone act on?

Answer 49

Also stimulates Na+ reabsorption at the distal tubule (but by a diff reflex pathway)

Question 50

How are H+ ions secreted?

Answer 50

Actively secreted from the tubule cells (not the peritubular capillaries) into the lumen - A/B balance

Question 51

Summarise Biomed Sessions vid on function of nephron