Kidney II Flashcards
Clearance and its use in renal physiology
Define Clearance
The volume of plasma that is cleared of a substance in a given time
Renal clearance = (U*V)/P
Why the clearance of insulin measures GFR?
However, why is Creatinine used clinically to estimate GFR
It's freely filtered It's not reabsorbed It's not secreted It's not metabolised It's easily measured
Creatinine is handled in a similar way to insulin, except that it’s slightly secreted - by the organic cation transporters.
It’s used clinically bc it’s an endogenous substance, and it doesn’t have to be administrated by IV.
How is effective renal plasma flow measured?
How is used this to calculate renal blood flow?
Renal plasma flow = PAH clearance. B/c it doesn’t go though the glomerular & peritubular capillaries.
Effective renal plasma flow (an underestimate) ~600ml/min.
BF = plasma flow / (1-haematocrit)
=~600 / 0.55
You can see that a huge amount of blood is entering the kidney
Define osmolality
What’s it’s importance to renal function?
Osmolality (mOSm/kg) - a measure of water concentration.
The higher the solution osmolality, the lower the water conc.
Plasma: 285-295
Urine: 50-1400
Osmolality is independent of temp
The main osmotically active solute in plasma is Na+ Plasma Na+ conc is 135-145mmol/l Na+ freely filtered at renal corpuscle [Plasma Na+]*GFR=amount filtered 140*0.125=17.5mmoles/min
Amount filtered: 25,200mmoles/day - majority is reabsorbed. This is important bc Na+ balance is linked to BP (LIV)
Where does salt reabsorption (active process) occur?
PT, Thick Ascending limb,
What transporters do each of these 4 tubule segments do they use?
From lumen of tubule to
PT: 65%. Filtrate -ve.
NHE3 (2 active trasnporter), Na+:K+ ATPase pump, Na+ nutrient symporter (down it’s conc grad)
Cl- transported b/w cells.
TAL: 25%. Filtrate +ve
Na+:K+:2Cl- co-transporter (Na+ moves down conc grad), Na+:K+ ATPase pump, K+ channel (K+ moves down conc grad, to lumen)
Na+ transported b/w cells.
DT: 2-5%. Filtrate -ve
Na+:Cl- co-transporter, Na+:K+ ATPase pump.
Cl- transported b/w cells.
CD: 5%. Filtrate -ve
2 cell types - Principle cells (Na+ transport)
- Interculated cells (H+ transport)
Na+ channel, Na+:K+ ATPase pump.
Cl- transported b/w cells.
Describe the water reabsorption process
-direct coupling of H20 reabsorption to sodium reabsorption
High to low across the plasma membrane
Depends on:
>Osmosis gradient
>Na+ reabsorption
>Tubule permeability
PT:
1) Na+ moves from tubular lumen to interstitial fluid downhill via Na+:K+ ATPase pump.
2) Causes decrease in local osmolairty in tubular lumen, and increase in interstitial fluid
3) B/c Na+ left, [H20] in tubular lumen increases, so moves from high to low to interstitial fluid via osmosis - binds to AQP-1 H20 channel or b/w cells (isotonic reabsorption).
Results in bulk flow of H20 into peritubular capillaries -H20 following the change in hydrostatic pressure gradient across the capillary wall.
Filtrate volume reduced but not osmolarity, b/c of the direct coupling of H20 + Na+.
How do we produce a concentrated urine?
-urine have higher osmolality than plasma
- We need to separate Na+ and water reabsorption
2. Generate a renal medulla interstitial fluid with high osmolarity to drive water reabsorption
Where does the separation of Na+ and H2O reabsorption occur?
Henle’s loop - 3 segments.
reabsorbs more salt (25%) than water (10%)
Flow is countercurrent (multiplier)
The limbs are separated by medulla
How does the separation of Na+ and H2O occur
In the ascending limb, salt reabsorption occurs via Na+:K+:2Cl- cotransporter.
Limb is impermeable to water, so water will not follow Na+ at this site. H2O stays in tubule.
Descending limb (from PCT) absorbs Na+ (secreted) via passive NaCl channel, and it loses H2O via AQP-1
How is the medullary interstitial gradient set up?
Loop of Henle is filled with filtrate that has the same osmolality as plasma (300).
In the ascending limb, activation of the pump for Na+ reabsorption will create an osmotic gradient across the wall of 200mOsm/l
In the descending limb, reabsoprtion of water creates a higher conc inside this tubule (400mOsm/l)
So Fluid entering loop has same osmolality as plasma (300). Fluid with high osmolality (400) has been pushed (flows) around loop to ascending. Fluid leaving loop has lower osmolality (200) than fluid entering.
Activiation of pump on ascending reduces osmolality more (300 & 150). Results in equilibration of water across descending (increased osmolality 350 + 500)
Outcome: been able to create a gradient of increasing osmolality in the descending limb towards the turn. This is mirrored by increase osmolality in the medullary interstitial fluid.
What’s the problem with the medullary interstitial gradient described?
How do we create a concentrated urine instead?
The fluid leaving the loop of Henle is dilute - it has a much lower osmolality than that of plasma, when the whole point was to generate a urine with a higher osmolality than plasma
Concentrated urine can happen with the use of Vasa Recta, which supply blood w/o washing the gradient away. Via counter-current exchange
Describe the counter-current exchange mechanism
Note: equal permeability to Na+ & H2O of the descending limb + ascending of vasa recta.
So when the Vasa Recta descends into the medullary interstitial w high osmolality, Na+ will be taken into the blood and H2O will leave in an attempt to equlibrate. However, when the ascending limb leaves the area the opposite happens.
Supplying blood to this area allows there to be a maintenance of this high osmolality that Loop of Henle has created in the medullary interstition.
Describe the recycling of Urea
High osmolality in fluid also generated by presence of urea (breakdown product of protein catabolism - nontoxic)
- PT - passive reabsorption
- LOH - apical secretion via UT-A2
- Inner medullary CD - apical reabsorption via UT-A1
~40% of urea filtered is excreted
(increasing osmolality in the interstitium towards medulla)
Concentrated urine is generated at the collecting duct - CD (controlled water permeability) descends into the area of high osmolality found in the medullary interstitium
What’s the difference between Tinicity and Osmolality
Tinicity - refers to conc of non-penetrating solutes
Osmolality - refers to conc of penetrating AND non-penetrating solutes
