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40 Renal Tubular Function
How dilute a urine would a person be able to excrete if they had a high water intake?
- the osmolarity can get as low as 50 mOsm/L
- this is ~1/6 that of normal plasma (which is normally ~300 mOsm/L)
What is the urine concentration of someone who has a typical water intake?
How concentrated a urine would a person be able to excrete if they had a low water intake?
- an extremely dehydrated person could excrete urine as concentrated as 1200 mOsm/L
- this is the maximum osmolarity
How is a dilute (watery) urine generated?
- reabsorption of water & ions in the first part of renal tubules is normal
- however in the late DT/CD, there is significantly reduced reabsorption of water as a result of low levels of ADH
What primarily determines the amount of ADH secreted from the posterior pituitary gland?
- PLASMA OSMOLARITY
- ↑ plasma osmolarity → ↑ ADH levels
- ↓ plasma osmolarity → ↓ ADH levels
Osmolarity Throughout the Renal Tubule During the Generation of DILUTE Urine
• fluid just outside the glomerulus is the same as the plasma minus proteins & cells, so it will have an osmolarity equivalent to plasma → 300 mOsm
• in the proximal tubule reabsorption of water & solutes is isoosmotic → 300 mOsm even though the tubular volume is drastically reduced
• in the thin descending limb water but no solutes are reabsorbed so the osmolarity increases
• in these conditions the medullary interstitium is 600 mOsm (not the maximum 1200), so at the tip of the loop of Henle tubular fluid equilibrates w/ the interstitial fluid → 600 mOsm
• osmolarity is reduced in the thin & thick ascending limbs (where the tubule is permeable to salt but not water) until filtered fluid is hypo-osmolar compared to plasma → 100 mOsm
• low ADH levels means the late DT/CD are relatively impermeable to water, so most stays in the renal tubule while there continues to be salt reabsorption → 50 mOsm of excreted urine
Reminder: Water Reabsorption Along Renal Tubule
- 67% (2/3) is reabsorbed in the proximal tubule
- 23% (1/4) in the thin descending limb
- NONE in any part of the ascending limb
- 0% (low ADH) → 10% (high ADH) can be reabsorbed in the late DT/CD
Excretion of what percentage of filtered water corresponds to the most amount of urine a person can excrete per day?
- 10%, this amount corresponding to the greatest possible amount the late DT/CD would potentially be able to reabsorb
- filtering 180 L/day, this would be the maximum urine output would be 18 L/day (what people w/ diabetes insipidus excrete)
What will a dehydrated person have in their kidney if they’re trying to conserve water?
1. high osmolarity of the medullary interstitium
2. high water permeability of distal tubule & collecting duct (due to presence of high ADH attempting to reabsorb as much water as possible)
What is the minimum amount of urine a person MUST generate on a daily basis?
- 0.5 L
- we must excrete 600 mOsm of solutes per day (half of which is urea)
- so b/c the maximum osmolarity of urine is 1200 mOsm, that’s where 0.5 L comes from
What makes up 40% of the 1200 mOsm maximum medullary osmolarity in the medullary interstitium when attempting to create a concentrated urine?
- UREA, a waste product from amino acid catabolism
- the kidneys must clear 25-30 gm/day
- 50% of filtered urea is excreted
Role of Urea in Creation of a High Osmolarity Medullary Interstitium
• the level of urea in the plasma is 4.5 mOsm
• its concentration increases in the proximal tubule b/c there the cells are less permeable to urea than they are to water; there’s a lot of water reabsorption that occurs, concentrating urea in the tubule
• its concentration continues to increase as the fluid makes its way down the thin descending limb & up the thin ascending limb b/c urea is ENTERING the tubule from the medullary interstitium (↑ [urea] in the thin portions of loop of Henle due to high permeability & high conc. in the medullary interstitium)
• most of the rest of the renal tubule, the thick ascending limb, the distal tubule, & the cortical collecting duct is impermeable to urea
So how is it that urea can contribute to the high interstitial concentration?
- b/c its concentration gradually increases as fluid carrying it passes through the renal tubule, when it finally makes it down to the collecting duct & can diffuse out of the tubule it DOES, down its concentration gradient, into the medullary interstitium
- urea sits in the proximal tubule as water flows → it diffuses into the thin limbs of the loop of Henle → it gets trapped in the thick ascending limb, distal tubule, & cortical collecting duct (as water flows out, so it becomes CONCENTRATED → then finally in the medullary collecting duct it can diffuse out down its concentration gradient into the kidney medulla
Why is the medullary interstitial osmolarity 600 mOsm/L when ADH levels are low & 1200 mOsm/L when ADH levels are high?
- at low ADH, the medullary collecting duct is less permeable to urea, meaning there is DECREASED diffusion of it from out of the renal tubule into the medullary interstitium
- more is washed out into urine & therefore not able to contribute to high interstitial osmolarity
After the high osmolarity of the medullary insterstitium is created (via that countercurrent exchange mechanism of water/solute reabsorption), how is it MAINTAINED?
via the Vasa Recta, which delivers blood to the medulla without “washing out” the solutes present in it
What effect do vasodilators have on the kidney?
- they reduce the ability of the kidney to CONCENTRATE the urine b/c they wash out solutes that are central to creating the high osmolarity of the interstitium
- vasodilators → ↑ blood flow → ↑ wash out of solutes →↓ ability to form concentrated urine
- the volume of plasma cleared of solutes/min, aka the clearance of all the osmolytes
- Cosm = Uosm*V / Posm
- Uosm = urine osmolarity (mOsm/L)
- Posm = plasma osmolarity (mOsm/L)
- V: urine flow rate (mL/min)
Free Water Clearance
the difference between urine flow rate & osmolar clearance
- CH2O = V - Cosm
- = V - (Uosm * V/Posm)
• is dependent upon Osmolar Clearance
• this number can be either positive or negative
• if it’s POSITIVE, it means that the urine flow rate is in excess of the osmolar clearance, meaning water excretion is greater than solute excretion
• if it’s negative, it means that the osmolar clearance was larger than the urine flow rate, meaning solute excretion is greater than water excretion
What does a positive free water clearance tell you?
a person is excreting more water than solutes
41 BP & Volume Regulation
What is the major way the body regulates extracellular Na+ concentration?
- by regulating the extracellular fluid volume
- it’s important to do so b/c abnormalities in Na+ concentration can cause neural & cardiac dysfunction, & Na+ is also the major determinant of plasma osmolarity
- if there are changes in extracellular Na+ concentration, the body can correct for these changes by changing fluid volume
What are the 2 regions in the hypothalamus that contain Osmoreceptor cells?
- 1. Organum Vasculosum
- 2. Subfornical Organ
- these areas contain nerve cells & when plasma osmolarity increases (i.e. when Na+ concentration increases), these cells grow & stimulate other nerves to release ADH
- (if osmolarity decreases they shrink)
- they ALSO stimulate thirst centers in the hypothalamus when
Where do signals from the cells of the Organum Vasculosum & Subfornical Organ go?
- to the Paraventricular & Supraoptic nuclei, also in the hypothalamus
- these are the sites where AVP (arginine vasopressin) also know as ADH is produced
- the hormone is then transported into the posterior pituitary for storage in vesicles at axon terminals
- when the nuclei cells are stimulated they release ADH into the blood
What will expansion of ECF (extracellular fluid) signal the kidneys to do?
- it acts as a signal for the kidneys to increase their rate of Na+ excretion
- the ECF [Na+] remains unchanged
- normal individuals can be in Na+ balance from an intake of 1-2 mMol Na+/day (ECF will be relatively low), to up to 200 mMol/day (ECF will be high)
What particular regions in the ECF compartment play a role in regulating Na+ excretion?
- those that contain ECF volume sensors
- “low pressure receptors” are located mainly in thoracic blood vessels & atria
- when these receptors pick up an ↑ in “central blood volume” they signal for an ↑ in Na+ excretion
- when they pick up a ↓ in “central blood volume” they signal for a ↓ in Na+ excretion
Pressure Sensors in the Heart
- #s refer to regions in the vasculature & heart itself where there are low pressure stretch (mechanoreceptors) receptors
- can pick up relatively small decreases in BP
Body’s Response to a Decreasing Effective Circulating Volume
• 3 different regulatory systems kick into gear
1. Renal Baroreceptors
2. Cardiac & Pulmonary Mechanoreceptors + Carotid Body & Sinus
3. Atrial Myocytes [actually this one is DOWNREGULATED in response to low effective circulating volume*]
end result of all these responses is to decrease Na+ excretion (in other words they increase Na+ reabsorption)
Cardiac/Pulmonary Mechanoreceptors & Carotid Body & Sinus
- low pressure receptors in heart & pulmonary vessels & high pressure receptors in the aortic arch & bifurcation of the common carotid a. send signals to the brain when they sense a a low effective circulating volume
- they stimulate the sympathetic n.s system, which will increase C.O. & constrict vessles
- they also send signals to the posterior pituitary to release ADH
- a low effective circulating volume results in a decreased GFR (less hydrostatic pressure enters the glomerular capillaries)
- ↓ GFR (↓ BP) stimulates the release of renin from JG cells
- renin will work through the renin/angiotensin/aldosterone system (RAAS) to produce Angiotensin II
Angiotensin II (ANG II)
- has 2 functions:
- 1. constricts BVs, raising the BP
- 2. stimulates the adrenal cortex to release aldosterone (whose major function is to ↑ Na+ reabsorption - therefore it also ↑ water reabsorption)
- [“water follows sodium”]
Simplistically, what happens if the body has a low plasma volume (dehydrated)?
- low plasma volume results in decreased afferent arterial blood pressure & increased activity of the renal sympathetic nerves
- these events stimulate juxtaglomerular renal granular cells to secrete RENIN
- renin converts angiotensinogen into angiotensin I
- angiotensin I is cleaved in the lungs by ACE (angiotensin converting enzyme) into angiotensin II
- angiotensin II stimulates the adrenal cortex to release aldosterone
- aldosterone increases reabsorption of ions (Na+) & water at the distal tubules & collecting ducts of the nephron
- result: increased water & sodium retention
- myocytes in the R Atrium when stretched (b/c of increased circulating volume) release ANP (Atrial Natriuretic Peptide)
- Natriuretic means eliminating Na+ in the urine
- end result of ANP release is to decrease circulating volume
- *it opposes the action of or is antagonistic to Aldosterone
Effects of Atrial Natriuretic Peptide (ANP)
overall: causes a loss of water by increasing amount excreted in the urine
1. ↑ GFR by constricting the efferent arteriole
- 2. inhibits Na+ reabsorption by decreasing resonance time of fluid in all parts of the renal tubule & inhibiting actual Na+ channels
- - quicker passage means Na+ has less time to be reabsorbed, so it isn’t & drags water w/ it when excreted
3. rapid flow through system inhibits renin release, which in turn inhibits ANG II
What happens if a person has ingested excess water (overhydration)?
- excess water results in decreased body-fluid osmolarity & an increased concentration of H2O
- these events stimulate osmoreceptors in the hypothalamus (brain gets involved) which activate the posterior pituitary to decrease production of ADH (WANT to diurese)
- less ADH means less water reabsorption by the collecting ducts
- result: increased water excretion