Urinary System Student Notes

Roles of the Kidney

1) Regulate blood oxygen capacity through erythrocyte production, viz., the release of erythropoietin (EPO), which we discussed earlier.

2) Affect blood pressure – we’ve already discussed this, viz., the

renin-aldosterone pathway, earlier this term. Note that this may, at times (e.g., high blood pressure), conflict with item no. 4, below.

3) Eliminate toxic substances, wastes, etc., while also

retaining/conserving important electrolytes and buffers, etc. 4) Maintain water and osmotic balance – principally, conserve

water by minimizing the loss of water in urine (i.e., making a urine more concentrated than blood), a major problem for terrestrial animals.

In this unit, now, we will address the last two parts.

Autoregulation

AfferentArterioleFlowRate(andGlom.FiltrationRate)

90 190Blood Pressure (mm Hg)

Autoregulation

Processes:

1) Myogenic – simple (systemic-type) vascular reactivity.

2) Tubuloglomerular feedback

adenosine constrictsMacula afferent densa arterioles cells NO dilates

Glomerular Filtration

Two fundamental factors affect Glomerular Filtration Rate:

1) afferent arteriole flow,which in turn are affected by:a) afferent arteriole pressure, andb) afferent arteriole resistance

2) efferent arteriole resistance

GlomerularFitration Rate

(GFR)

Afferent Arteriole Pressure

GFR

Afferent Arteriole Resistance

GFR

Efferent Arteriole Resistance

backpressure maintainsglomerular pressure

flow rate diminishessignificantly

Glomerular Filtration

Those signals affecting GFR include:

Vasoconstrictors (gen., reduces GFR and incr. blood vol.): Sympathetic ANSAngiotensin II – (part of Renin-Aldosterone, but here

direct effect) – also helps reabsorb water in PCT.ADH (in addition to effects on collecting ducts – later)Adenosine (see tubuloglomerular feedback, earlier)Endothelin

Vasodilators (gen., increases GFR and reduc. blood vol.): Atrial Natriuretic Peptide (ANP)Glucocorticoids (& Dopamine = inhibits Renin secretion)NO (see tubuloglomerular feedback, earlier)Prostaglandins (important, prevents ischemia)Kinins

Fick Principle of Mass Balance

Fate of any excretable substance

Arterial inputVenous output

Ureter’s Output

or, InputArt. = OutputVen. + OutputUr.

Note: the “mass” of asubstance is afunction of flow rate and concentration.

Fick Principle of Mass Balance

Thus, InputArt. = OutputVen. + OutputUr.

can be rewritten as

[conc. X flow]Art. = [conc. X flow]Vein + [conc. X flow]Ur.

Renal Clearance Rate:Amount of plasma (as it passes through the kidney)that is completely cleared of a substance per unit time

Theoretical – never happens !!!!But we use it as a measure of Glomerular Filtration Rate.

Fick Principle of Mass Balance

Renal Clearance Rate:

C = [conc. X flow]ureter / [conc.]Artery

This Clearance Rate, C, reflects the GFR for biologicallyinert substances – by inert, we mean:1) the substance is not synthesized 2) the substance is not metabolized

these mean that any amount injected into the patient willnot be changed except by renal excretion.

3) the substance is not secreted (convoluted tubules) 4) the substance is not reabsorbed (convoluted tubules) 5) the substance is freely filtered in the glomerulus these mean that the only excretory mechanism operating onthe substance will be glomerular filtration.

Fick Principle of Mass Balance

Renal Clearance Rate: What substance meets these criteria? Inulin (a plant sugar) C = [conc. X flow]ureter / [conc.]Artery an example: 50 mg/ml X 2 ml/min. = 100 mg/min. = 25 ml/min = C

4 mg/ml 4 mg/ml Question: Why is the ureter concentration (50 mg/ml) so much greater than the arterial concentration (4 mg/ml)?

Fick Principle of Mass Balance

Renal Clearance Rate:

What substance meets these criteria? Inulin(a plant sugar)

C = [conc. X flow]ureter / [conc.]Artery

an example:

50 mg/ml X 2 ml/min. = 100 mg/min. = 25 ml/min = C

4 mg/ml 4 mg/ml

Question: Why is the ureter concentration (50 mg/ml) somuch greater than the arterial concentration (4 mg/ml)?

water reabsorption

Fick Principle of Mass Balance

Inulin establishes the GFR – using other substances (“x”)can indicate secretion and/or reabsorption (convoluted tub.)

Example:

PAH is filtered but also secreted. Its rate, CPAH, will begeater than that of Inulin, CInulin.

In summary:

If Cx < CInulin substance x is reabsorbed*, too.

If Cx > CInulin substance x is secreted*, too.

If Cx = CInulin substance x is only filtered.

* reabsorption (or secretion) = |Cx – CInulin|

Fluid Volume and Osmolarity

Clinically, hypo- and hyperosmoticity affect cell swelling and shrinkage, initially manifesting brain and other neurological problems.

ADH and ANP (in opposition) are the body’s initial responses (other hormones work subsequently): Vasopressin (ADH) ANP blood levels

osmolarity volume & pressure

1) increases water permeability in collecting duct & DCT 2) increases reabsorption of Na+ in ascending limb 3) increases urea permeability in collecting ducts 4) increases act. transp. of salt out of the ascend. limb

Summary of Convoluted Tubules(i.e., secretion and reabsorption)

Proximal Convoluted Tubule About 2/3 of water reabsorbed (by Angiotensin II)Na+ reabsorptionProtein reabsorptionglucose reabsorptionorganic ion secretion

Distal Convoluted Tubule Reabsorbs Na+, Cl-, water, and Ca2+Secretes K+ (Aldosterone!)

Cortical vs. Juxtamedullary Nephrons

Cortical (more than 4/5 of your nephrons):Of little use for significant water retention; mainly contributes to reabsorption and secretion of substances above and beyond

those initially separated from blood by filtration.

Juxtamedullary (less than 1/5):Besides the same as Cortical, also plays a major role in water retention – regulating whether you’ll produce a dilute or concentrated urine – by creating the Salt gradient through the depths of the medulla region and enabling the reabsorption of water in the Collecting tubule, and with the Vasa recta, being able to reconstitute the blood with this recovered water.

Cortical vs. Juxtamedullary Nephrons

Because of this paucity of Juxtamedulary Nephrons in humans, we are ill-adapted to

live in an arid climate. You will die if you’re stranded:

1. in a desert (no water to drink)2. or at sea (left to drink only sea water)

whereas other mammals thrive in this places.Why?

Adaptations to sea/desertBoth marine (sea water) and desert

environments will dessicate the body:All mammals adapted to these habitats have an abundance of Juxtamedullary nephrons, and can produce highly concentrated urine,

thus eliminating wastes (and also excess salts absorbed by drinking sea water to replenish

lost water) using minimum amounts of water in the urine (i.e., more conc. than sea water).

Interesting factoids:

The Kangaroo Rat, Dipodomys sp., of the american S.W. deserts, never drinks water. It meets its total need for water from just “metabolic water” (a byproduct of carbohydrate metabolism – the last step, combining sugars’ hydrogen and the oxygen you breathe into new water molecules. And it produces a saturated urine, so concentrated that it crystalizes immediately.

Sea reptiles and birds, which must drink sea water, do not have such effective kidneys. Despite having to drink sea water, they can eliminate the excess salts with glands (e.g., sea turtles, crocodiles, etc., use their lacrimal glands; birds use a nasal gland) that produce an extremely salty secretion.

To achieve the goals of controlling water loss, the medulla uses two countercurrent systems: 1) Countercurrent Multiplier:

To create an osmotic gradient in the medulla’s tissues.

2) Countercurrent Exchanger: For the Vasa recta to absorb water without also carrying away the salt.

These two countercurrent systems are used to create a salt gradient. It is only with this gradient that the kidney can ultimately create a urine much more concentrated than the blood, by reabsorbing and retaining a great proportion of water from the filtrate, while eliminating the necessary amount of waste and salts.

Cortex-Medulla edge ___

Bowman’s capsule

Calyces

Shading indicates salt gradient:

darker = moreconcentrated

Proximal and Distal Convoluted Tubules

Co

llecting

Du

ct

Loop of Henle

Asc

end

ing

Lim

bDescen

din

g L

imb

The walls of this descending limb are freely permeable to water, but not to salt.

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

Loss of water by osmosis increases concen.

Filtrate stays isosmotic with surrounding tissues: ~1,200 by this point

Iso-osmotic, ~320

Water, by osmosis

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

With this very concentrated (i.e., salty) filtrate, the walls of ascending limb (impermeable to water) pump out salt by active transport, eventually diluting the filtrate to very dilute levels, even hypo-osmotic to blood; while leaving lots of salt in the medulla’s interstitial tissue.

~100Iso-osmotic, ~320

1,200

Salt,by Active Transport

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

With this very concentrated (i.e., salty) filtrate, the walls of ascending limb (impermeable to water) pump out salt by active transport, eventually diluting the filtrate to very dilute levels, even hypo-osmotic to blood; while leaving lots of salt in the medulla’s interstitial tissue.

In fact, within limits, this can be thought of as a positive feed back loop: as more salt is pumped out here, the salt gradient increases in the interstitial tissue, and this makes the fluid in the descending limb become more concentrated – this facilitates even more active transport pumping of salt out of this ascending limb.

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

300100

Three seemingly obvious questions:1) What did we accomplish? We started with a filtrate

at 300, and ended with a filtrate at 100. Clearly we went in the wrong direction if we’re trying to make a more concentrated urine! After all, “1,200” would be a nice end product concentration.

2) Why didn’t we just stop at the bottom of the loop, at 1,200, and excrete that as our final urine?

3) How do we have a salt gradient from this? Doesn’t the amount of water and salt lost cancel each out?

1,200

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

Vasa recta

flows from the efferent arteriole of the glomerulus

Remember that this is the Renal Portal Vein system!

This Vasa recta consists of capillaries, and follows immediately the capillaries of the glomerulus.

And blood from the glomerulus has a high protein concentration, osmotically unsuitable to be released into general circulation – the lost water must first be reconstituted into the blood!

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

This region contains large amounts of salt (which should be retained to produce the salt gradient) plus copious amounts of water which must be removed (1) to avoid diluting this salt gradient, and (2) to reconstitute the blood which has, until now, lost ~180 liters of water per day.

Thus, the Countercurrent Exchanger!

This has to address the problem of having the blood extract large amounts of water from the tissues (from the descending limb of the Loop of Henle and the Collecting Ducts) while not also taking away the salt that is accumulating – and thus protecting the established salt gradient.

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

Important Note:

An ideal countercurrent exchanger is one that will exchange one substance for another on each limb of the loop. E.g., salt would be absorbed into, while water would be lost from, the blood on the first limb; and salt would be lost, while water would be absorbed, in the second limb – and each would counterbalance the other. Perhaps this is what you were taught in General Biology, or in H.S. A.P. Bio?

But in reality, fortunately, this is not the case here – it doesn’t work as perfectly as that – otherwise, nothing useful would be accomplished.

In reality, proteins in the blood, made more concentrated because they were left in the blood as filtration removed a lot of everything else in the glomerulus, plays an important role in biasing water’s movement in each limb, as I’ll explain subsequently….

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

Blood first flows down into the depths of the salt gradient – as it passes through saltier tissue, more salt diffuses into the vessel, increasing its salinity while staying iso-osmotic at every level.

300

1,200

salt

While salt enters the blood vessel, some water does osmotically move from the blood to the interstitial tissue, but not as much as it otherwise should – the blood proteins (highly concentrated) “hold” much of the water back from such movement, and there’s more salt diffusion into the blood than osmosis of water out of the blood.

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

However, as the blood rises up the opposite limb of the Vasa recta, it passes through progressively less concentrated tissue and thus salt begins to diffuse out of the blood, again keeping the blood iso-osmotic every step of the way.

300

1,200

salt

And likewise, as salt diffuses out of the blood, much more water will actually flow, osmotically, into the blood (as we’ll shortly discuss).

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

And most of that salt that left that limb, together with any more salt pumped from the ascending limb of the Loop of Henle, winds up diffusing back into the first limb of the Vasa recta.

Most of the salt is caught in a “vicious cycle” or “endless loop” – i.e., it just goes in the descending blood and comes out of the ascending blood – and thus trapped here, it creates the salt gradient in the medulla.

300

1,200

salt

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

Meanwhile, water accumulating in the tissues from the descending limb of the Loop of Henle as well as the Collecting duct (to be discussed next) also enters this limb – its osmotic flow is promoted by the blood proteins (made more concentrated by the loss of water from the blood – i.e., Filtration – in the glomerulus).

300

1,200

water

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

300

1,200

So, remember that the concentrated blood proteins bias the movement of water, inhibiting its loss in the downward flow, and yet facilitating its absorption in the upward, return flow.

Thus, while salt is captured in a “recycling loop” in this interstitial tissue, more water is absorbed than lost in this “down-then-up” flow, and this net gain of water into the blood enables the recovery of the water needed to fully reconstitute the blood to its original osmotic concentration.

Bottom line: we carry away a lot of water and very little salt!

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

One important note:

Although the filtrate entered the distal convoluted tubule at ~100, the surrounding tissue in the cortex is at about 300, so in fact this portion of the tubule will allow an osmotic draw of water from the filtrate, increasing its concentration back up to ~300 again, where it will enter the top of the Collecting Duct.

100

300water

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

And as a result, the urea (like salt) also becomes concentrated in the lower portions of the medulla by becoming trapped in a recycling loop – as shown below:

There are only two areas that are freely permeable to urea: the lower portions of both the descending Loop (where it isn’t concentrated), and also the Collecting Duct (where it is concentrated, because the urine is concentrated)….

Osmo-ticity:

300

400

500

600

700

800

900

1,000

1,100

1,200

So now we have a salt gradient extending down through the interstitial tissue of the medulla.

But we still have created a filtrate that is hypoosmotic, or at best only iso-osmotic (i.e., ~300), and not nearly concentrated enough to carry away wastes, etc., without also dangerously dehydrating the body from a copious flow of water.

We still have to make, as our final urine product, a much more concentrated filtrate.

This is accomplished in the next step …

… during the passage of the filtrate down, through the salt gradient, inside the Collecting Duct!

The Collecting Duct has walls that may or may not be permeable to water – depending on the presence of certain hormones, especially Vasopressin or ADH.

Remember that the salt gradient in the surrounding tissue would osmotically draw water out of the Collecting Duct (if the walls permit this) making the filtrate more concentrated.

Remember: With more ADH…• Not only is more water reabsorbed in the

Collecting Duct as well as in the DCT

but also …

• the medulla’s tissues develop a steeper concentration gradient (to facilitate that final water reabsorption), because:– more salt is pumped out of the ascending limb

of the Loop of Henle, and thus recycled; – more urea is recycled and concentrated in the

deeper zone of the medulla

Dialysis

(from First Semester):

bathe blood in fluid that is balanced for all desireablesubstances – no concentration gradient, no net loss – butlacks those wastes that need to be removed. The resultingconcentration gradient of the wastes will remove them fromthe blood.

Two types of dialysis:1) Hemodialysis2) Peritoneal dialysis