Renal Physiology: Glom and Tub function

Question 1

What determines glomerular net filtration pressure?

Answer 1

GHP-oncotic pressure- CHP

only 20% of capillary plasma is filtered

thus is sodium levels will kill you, and this is managed by renal water handling, GFR must be maintained

Question 2

What happens to GFR when you alter systemic blood pressure?

Answer 2

Nothing, within limits.
Due to kidney autoregulation.
Alters the efferent and afferent arterioles

Question 3

How does arteriolar dilation/constriction alter GFR?

Answer 3

AA constriction- decrease GFR
AA dilation- increase GFR
EA constriction: increase GFR

Question 4

What are the mechanisms of autoregulation?

Answer 4

Extrinsic: Renin- angiotension II (EA constriction); ANP/BNP (AA dilation); SNS (AA constriction)

Intrinsic: myogenic (increased arterial pressure causes AA stretch, causing constriction. keeps GFR stable); Tuboglomerular feedback (macula densa cells monitor distal tubule NaCl, if high, AA constriction (to decrease GFR)

Question 5

Tuboglomerular feedback

Answer 5

When GFR is too high -> more NaCl passes macula densa (poxy for flow) -> paracrine signals released -> afferent arteriole constricts -> decrease in GFR

Question 6

Renin angiotensin II

Answer 6

low GFR -> macula densa cells sense low NaCl -> paracrine signals -> JG cells release renin -> angiotensin II -> EA constriction (increase GFR) AND aldosterone release to increase Na+ reabsorption from distal tubule, increase blood volume.

Question 7

Proximal tubule (and transport mechanisms)

Answer 7

Filtrate reabsorption! (100% glucose, 66% other stuff (ions etc, 90% bicarbonate)

Transcellular: primary AT; secondary AT driven by co-transport or antiport

Paracellular

Na+/K+ ATPase critical

Question 8

Active transport in early proximal tubule

Answer 8

• Na+ gradient established by ATPase in basal -membrane.
• Na+ intake by symporters (glucose) in brush border
• Na+ diffuses into capillary bed
• water follows through leaky tight junctions paracellularly. (solvent drag)

Because water follows osmolality remains constant

Question 9

Bicarbonate

Answer 9

pH buffer in body and needs to be reabsorbed in proximal tubule.

depends on membrane bound + cytosol carbonic anhydrase to form CO2 which will freely diffuse.

Question 10

Reabsorption of bicarbonate in proximal tubule

Answer 10

• Soidum hydrogen exchanger increases lumen H+
• formation of carbonic acid
• membrane bound CA breaks down to CO2 + H2O
• in cytosol CO2 is hydrated as well as some CO2 formed by metabolism to form carbonic acid
• this dissociates to bicrabonate and H+
• bicarbonate is transported across basolateral membrane.

Overall lumen acidification drives bicarbonate absorption. (90% of filtrate reabsorbed)
Dysfunction of this can leads to proximal tubule mediated acidosis.

Question 11

Bicarbonate generation

Answer 11

• PT cells metabolise amino acids (glutamine) into ammonium and bicarbonate
• ammonium is secreted into the lumen by soidum antiport (sodium in)
• bicarbonate transported into blood
• an increase in ECF H+ will cause more glutamine metabolism

Question 12

Fanconi syndrome

Answer 12

genetic defect where PT cells can not absorb filtrate substances leading to loss of electrolytes in urine.

Question 13

Chloride reabsorption in LATE proximal tubule

Answer 13

• chloride becomes concentrated in LPT due to prior reabsorption of water and solutes
• Cl- conc in lumen > Cl- conc in ECF
• Paracellular transport through leaky tight junctions
• lumen becomes electropositive, inducing paracellular Na+ reabsorption

Question 14

Proximal tubule secretion

Answer 14

Organic anions (some drugs like penicillin, bile salts) and organic cations (creatinine, some other drugs) are moved from the blood into the PT cells and co transprted with things such as Cl- (anions) or H+ (cations)

Way of removing xenobiotic agents from diet, drugs or environment.

Question 15

Loop of Henle key roles

proximal straight tubule; thin descending limb; thin ascending limb; thick ascending limb

Answer 15

Water reabsorption
urine production and concentration
May work by proposed countercurrent mechanism and passive hypothesis

Question 16

Nephron and medulla alignment as well as where water moves from, Slide page 23

Answer 16

There are long and short loop nephrons.
Short loop nephrons only have the loop in the outer medulla. Long loop nephrons have their loops in outer and inner medulla.

The outer medulla uses NaCl and the inner medulla uses NaCl and urea.

Bear in mind the the medulla has a salt gradient, with the inner medulla with a higher salt conc.

water will come put of the THIN LIMB and collecting duct in the medulla

Question 17

Sodium movement through loop of Henle

Answer 17

-the third of remaining sodium will flow through the nephron until the TAL.
- Sodium is extruded by means of the Na+/K+ ATPase, and is mediated by the NKCC2 which brings in one sodiuma nd potassium and 2 Cl.
-ROMK recylces K+ and puts back in the lumen.
-Tight junctions are water tight, so osmolality in interstitium is raised.
(NOTE furosemide targets NKCC2, is a diuretic)

THE SINGLE EFFECT

Question 18

Countercurrent multiplication (outer medulla as where the TAL’s start)

Answer 18

• When filtrate reaches TAL, salt extrusion into medulla causes an increases in ECF osmollaity and decrease in TAL osmolality.
• In thin descending limb, water will move out, raising the TDL osmolality.
• As fluid from the TDL moves through through the TAL, the higher osmalality fluid has its salt extruded. The further up the TAL the less salt extruded. This will cause more water to be absorbed from the TDL. Continuous.

Question 19

Role of the vasa recta

Answer 19

If water is moving into the ECF why doesn’t it dilute it?
The vasa recta carry blood opposite to the direction of tubular flow. As blood flow descends, loses water due to gradient, but a it ascends, water is reabsorbed as it is by TDL where water is extruded from the tubule.

note that slow blood flow offers optimal exchange, and increased flow causes wash out (takes away salt from the gradient), as in decreased concentrating ability.

Question 20

Early distal convoluted tubule

NB this and TAL are diluting segments

Answer 20

• Tubular fluid leaving the TAL is dilute due to CC
• further dilution occurs here, by Na+/Cl- symport driven by Na+/K+ ATPase.
• is water tight

Transporter blocked by thiazide diuretics (hypertension and heart failure meds) (lower ECF sodium, less water so lowers BP)

Question 21

Gittleman syndrome

Answer 21

Defect in Na/Cl symport. Na+ and Cl- wasting

hyperaldosteronism, and resultant hypokalemic alkalosis.

Question 22

principal cells in LDCT; Connecting tubule and collecting duct

Answer 22

Reabsorb Na+ and secrete K+
Sodium reabsorbed by ENaC (drievn by the ATPase).
Makes lumen electronegative, driving K+ secretion into tubule by ROMK. So more lumenal Na+ more K+ secretion.

So assume thiazide diuretics.increase in lumenal Na+ so increase in K+ secretion. Can cause hypokalaemia.

Also potassium sparing diuretics such as amiloride

Question 23

Liddles syndrome

Answer 23

Mutation causing increased ENaC. More sodium reabsorbed, leading to increased ECF volume, hypertension thanks Joe.

Question 24

Aldosterone and principal cells

Answer 24

Stimulates ENaC to cause sodium reabsorption and K+ secretion by gene expression. Upregulates ENaC.

spirolactone blocks spirolactone and is a weak K+ sparing diuretic. early late affect (some early activators and late activators)

Question 25

Intercalated cells (same place as principal)

Answer 25

-Important for acid base balance and K+ absorption
-usually secrete H+ by means of H+ ATPase and H+/K+ATPase.
-Some of this H+ can be used to reabsorb bicarbonate and generate bicarbonate. Acid base balance as removes acid.
so pH is about 4.5 in collecting duct

Question 26

pH balance

Answer 26

CO2 in equilibrium with bicarbonate and H+ determine our pH
CO2 is produced by metabolism and removed by the lungs.
H+ is from metabolism in diet and is removed by the kidneys.
The kidneys generate and retain bicarbonate

Assume food ingestion. H+ depletes bicarbonate source and raises H+ so kidney generates new bicarbonate, retains filtered and removes acid

Question 27

Diffusion trapping of ammonium in collecting duct

Answer 27

• Excess H+ after bicarbonate reabsoprtion combines with NH3
• NH3 freely moves across cell mmebranes and will combine with excess H+ in the lumen to form charged ammonium. Is charged so will not move through the membrane and is thus another way in which H+ is lost.

Question 28

LDCT, connecting tubule and cortical collecting duct water reabsoprtion and outer medulla.

Answer 28

depends on ADH levels which inserts apical aquaporin 2 receptors. reabsorbs water.
High ADH causes conc urine.
rapid response
far greater in medulla due to greater osmolality in ECF

Question 29

How is the osmotic gradient established in the inner medulla/ long loop nephrons.

Answer 29

1) At high ADH, water is reabsorbed and urea conc is high in collecting duct.
2) ADH increases urea and water permeability of inner medulla and CD (CD is always permeable to urea)
3) urea deposited in interstitium. Water causes salt conc to lower.
4) NaCl moves out of the tip of AL into ECF

note that vasa recta helps preserve osmotic gradient.

Question 30

Low ADH and passive hypothesis

Answer 30

• Low ADH means little water is reabsorbed in cortical CD etc, so urea conc does not increase.
• inner medullary CD is permeable to urea still
• urea of ECF will exceed CD urea so urea will be lost, and wash out occurs.

as long as ADH is low inner medulla urea conc is low.