Lecture 5: Nephron function 1

Question 1

Describe the change in filtrate composition as it passes through the nephron:

Answer 1

• Renal corpuscle = No absorption, pH 7.4, 100% Glucose, Na, Cl, K, Water
• PT = Bulk absoprtion, Remaining: 0% Glucose, 33% Na, Cl and water, 30% K. pH Dropped to 6.7
• Loop, DCT, CD = Everything continues to drop / absorbed. BUT K increases slightly in the CD. pH has dropped to 4.5

Question 2

What are starlings forces?

Answer 2

The the balance of hydrostatic and colloid oncotic forces between the plasma and interstitial fluid.

• Govern movement of water and solutes b/w plasma and intersitial fluid (WITHIN ECF)
  i. e Hydrostatic pressure forces water and solutes out of blood, but plasma proteins that arent filtered exert oncotic pressure inwards.

Question 3

With starlings forces what happens in normal capillaries?

Answer 3

Normal capillaries: Small outward fluid shift (collected by lymphatics)

Question 4

Describe the filtration forces of the glomerulus:

Answer 4

~10mmHg net filtration pressure = (Glomeurular hydrostatic pressure - (Oncotic prressure (back in) + Capsular hydrostatic pressure)

Question 5

What is the glomerular filtration rate and how much of the total plasma volume in the glomerular capillaries is filtered?

Answer 5

125ml/min for both kidneys

~20% of total plasma volume in glomerular caps is filtered.

Question 6

Why is GFR (glomerular filtration rate) so important?

Answer 6

For the kidney to tightly regulate ECF osmolality and pH it needs to ensure constant GFR.

Primary regulation of GFR is via changes in glomeular hydrostatic pressure

Question 7

How does systemic blood pressure influence GFR?

Answer 7

Changes in systemic blood pressure dont change GFR because of renal autoregulation

(Renal autoregulation can only occur over a set range of MABP, beyond these limits (pathological blood pressures) GFR changes.

Question 8

What does renal autoregulation involve?

Answer 8

Feedback mechanisms that cause ither dilation or constriction of the afferent arteriole or constriction of the efferent arteriole.

Macula densa cells of the DCT sense NaCl and release ATP to change the aff or eff art diameter.

Question 9

What are some extrinsic mechanisms of renal autoregulation?

Answer 9

Renin-ANG2 = Constriction of efferent art. (inc. GFR)
ANP and BNP = Dilatation of afferent art. (inc. GFR)
SNS = Constriction of afferent art (Dec. GFR)

Question 10

What are the intrinsic mechanisms of GFR?

Answer 10

Myogenic : Increased art. pressure strethces the afferent arteriole inducing it to constrict = Offsets pressure increase and keeps CFR stable

Tubuloglomerular feedback: Macula dense cells monitor NaCl levels in distal tubule, if high they signal to the afferent arteriole to constrict = Decrease GFR (returning CFR to stable point)

Question 11

Describe the RAAS regulation of GFR in a flow chart

Answer 11

Dec. GFR -> Sensed by macula dense which release paracrine factors -> JG cells release renin -> ANG2 = Afferent art. constriciton (inc. GFR) and aldosterone release -> Increases Na reuptake from distal tube and increased BV = inc. GFR

Question 12

Describe the response of lowered BP to GFR

Answer 12

Question 13

Describe the SNS relation to maintaining GFR

Answer 13

Low Na or lower perfusion of brain triggers increased SNS to kidney which results in:

• Inc. Renin from JG cells
• Inc. PT Na and water reabsoprtion
• Decreased renal blood flow; afferent art. constriction, Dec GFR.

Acts to retain Na and water in body (maintain BP) (WHEN SEVERE SHOCK HAS OCCURRED)

Question 14

Whats absorbed in the PT?

Answer 14

• ~66% water and inorganic ions
• ~100% glucose and AA
• 90% Bicarb

Question 15

What are the transport mechanisms in the PT?

Answer 15

Transcellular

• Primary active transport
• Secondary active transport, drive by another gradient
• Co transport or symport
• Countertransport or antiport

Paracellular - b/w cells (passive)

Question 16

What are the predominant transporters in the PT?

Answer 16

Na couples transporters are predominant therefore Na/K ATPase function is critical (90% ATP is consumed here)

Question 17

Describe some transporters in the PT:

Answer 17

Na/K ATPase drives:
- Na/glucose symporters and antiporters. i.e Na down its gradient pulls glucose with it against its gradient

Water follows Na by paracellular osmosis via leaky junctions, some solutes i.e K follow this via solvent drag

Because water follows NaCl osmolality in the lumen remains constant.

Question 18

How is Bicarbonate re-absorbed in the PT?

Answer 18

• HCO3 is a key pH buffer thus needs to be reabsorbed from filtrate but cannot cross membrane. Thus brush border contains carbonic anhydrase that forms H2O and CO2 that freely diffuse across the membrane

This is why the pH drops to 6.7 in the PT

Question 19

What happens to CO2 when it enters the cell?

Answer 19

It is hydrated to form HCO3 and H+.

Bicarb transported across the basolateral membrane by transporters

THUS PT dysfunction causes PT acidosis due to loss of HCO3 in urine.

Question 20

How does PT generate new bicarb?

Answer 20

• PT cells metabolise glutamine to ammonium ion and bicarbonate
• Ammonium is secreted into the lumen by Na/NH4 exchanger.
• HCO3 is transported into the blood
• An increased in ECF [H+] increases renal glutamine metabolism (Increases HCO3 production)
• New HCO3 is a key function, as most PT H+ secretion that could (in theory) be used to regulate pH is instead used to reabsorb filtered HCO3

Question 21

What is fanconi syndrome?

Answer 21

Either heriditary of acquired, results from an impaired ability of the PT to reabsorb HCO3, Pi, AA, glucose and low-MW proteins, resulting in increased urinary excretion of these solutes.

Question 22

Describe Cl reabsoprtion in the late proximal tubule

Answer 22

• Cl becomes concentrated in the late proximal tubule due to the prior reabsorption of water and solutes in the early tubule
• [Cl] in lumen > [Cl] in ECF
• Cl moves down its concentration gradient via leaky tight junctions (paracellular)
• Lumen becomes electropositive -> Inducing paracellular Na+ reabsorption

Question 23

Whats secreted in the proximal tubule?

Answer 23

Organic anions and organic cations are secreted in the PT

• Clearance of xenobiotic agents ingested from the diet, or environment

Just understand that drugs are excreted

Question 24

What is the function of the loop of henle:

Answer 24

• Functions to produce urine that is more concentrated or more dilute than plasma
• Not clear how it works: Countercurrent and passive hypothesis theories
• Concentration and volume of urine can very dramatically

Question 25

What is found within the interstitium of the medeulla that contributes to the function of the loop of henle?

Answer 25

Osmotic gradient

• Outer medulla : 300-600mOsm/L
• Inner medulla : 1200mOsm/L

Question 26

What creates the high osmotic gradient?

Answer 26

NaCl and Urea

Question 27

What transporters are found in the short loop nephrons, where the loop of henle are in the outer medulla?

Answer 27

• NKCC2 and Na/K ATPase transfer Na to ECF
• ROMK recycles some K (back to filtrate)
• Tight junctions are water tight (not leaky)

= ECF becomes hypertonic compared to filtrate i.e 310mOsm/L vs 290

Question 28

What drugs targets NKCC2 in the short loops?

Answer 28

Furosemide

Question 29

Describe what happens in the counter current theory for loop of henle?

Answer 29

Applies to short loops in outer medulla

• Water is drawn from filtrate into interstitium, concentrating the filtrate as it descends the loop
• Ions are then drawn into the intersitium in the ascending loop, lowering the filtrate conc. as it ascends.

= Inc. interstium conc. as you descend.

Vasa recta carries blood in opposite direction and does opposite of this:

Countercurrent multiplication system

Question 30

What does the water go in the countercurrent multiplication mechanism for the short loops?

Answer 30

Vasa recta

• Carries blood counter to the direction of tubular flow
• Countercurrent exchange system prevents wash out of gradient
• i.e does opposite, water goes out and solute enters the blood as it descends, vice versa as it ascends

Question 31

How does the countercurrent mechanism change with changing blood speed:

Answer 31

• Slow blood favours optimal exchange
• Increased flow (i.e large increases in art. pressure) cause wash out and lowers urine concentrating ability

Question 32

Whats happening in the early distal convoluted tubule:

Answer 32

• Na/Cl transporter further dilutes tubular fluid
• Tight junctions dont allow water movement
• ‘Diluting segments’

Question 33

What targets the Na/Cl transporter in the distal convoluted tubule?

Answer 33

Thiazide diuretics