renal physiology origin of the hyperosmotic renal medulla

Origin of the Hyperosmotic Renal Medulla

continuing from last time

PHYSIOLOGY 451

RENAL PHYSIOLOGYDr. Michael Fill, Lecturer

[email protected]

Origin of the Hyperosmotic Renal MedullaPage 62 in the Renal syllabus

Medulla is hyperosmotic but there is also an osmolarity gradient.

CortexMedulla

mOsM

300400500600700800900

10001100120013001400

The 3 Essential Elements:1) Active Na+ transport in thick ascending limb of loop. ( Overall, the loop always reabsorbs more Na+ than H20 )

CortexMedulla

mOsM

300400500600700800900

10001100120013001400

Na

NaNaNaNa

NaNa

H20H20H20H20H20

CountercurrentMultiplication

H20 reabsorbed

Na+

reabsorbed



2) Unique arrangement of medullary peritubular capillaries. ( The vasa recta loop down into the renal medulla)

CortexMedulla

mOsM

300400500600700800900

10001100120013001400

Vasa RectaBlood Osmolarity

IN = OUTHair-pin looparrangementpreserves medullaryosmolarity



2) Unique arrangement of medullary peritubular capillaries. ( The vasa recta loop down into the renal medulla )3) Recycling of urea between loop and collecting duct. ( Urea provides about half of the high medullary osmolarity )

CortexMedulla

mOsM

300400500600700800900

10001100120013001400


UreaRecycling

Urea Recycling: Keeps “dumping” urea (solute) back into medulla.

Rate of “dumping” depends on urea level in the tubular fluid (faster when higher).

Tubular Fluid Osmolarity Changes along Nephron

Percent filteredH20 Remaining

Hypo-osmoticto plasma

Approaches osmolatity of interstitium in cortex

Approaches osmolatity of interstitium in medulla

Iso-osmoticto plasma Dilute

urine

Conc.urine

Regulation of Sodium and Water Excretion( Lecture 5 … page 66, renal syllabus )

….. essentially same as…..

Regulating Plasma Volume and Osmolarity

Kidneys excrete salt and water

Since the amounts of salt and water in body define blood volume & osmolarity,

Kidney’s control blood volume and body fluid osmolarity.

Renal Role in Blood Pressure Regulation

Short Term BP Control: seconds/minutes classic baroreceptor reflex sympathetic output changes vascular resistance

Medium Term BP Control: minutes/hours renin release renin promotes angiotensin II formation circulating angiotensin II changes vascular resistance

Long Term BP Control: hours/days changes in total body salt & H20 changes blood volume

The Kidney’s Role: 1) renin release (min/hrs) 2) controlling blood volume (hrs/days)

Blood volume changes when H20 moves in or out of the plasma.H20 always moves down osmotic gradients.

CONCEPT: If you control Na, then you control blood volume.

Most abundant osmotically active particle in plasma is Na+.Control of Na = control of H20 movement = Control of volume

Regulation of Na+ & H20 Balance

First a Conceptual Overview

Parallel BulkHandling

DifferentialHormonal

Fine-Tuning

PressureNatriuresis

Aldosterone ….. Na ADH ….. H20

Regulation of Na+ Balance

Pressure NatriuresisDefinitions: Natriuresis = Na+ excretion in Urine

Pressure Natriuesis is caused by increased blood pressure & associated increase in GFR.

MoreIN

MoreOUT

Simply Hemodynamics: More IN = More OUT No independent treatment of Na+ & H20 Good for simple bulk volume control

Some Murky Mechanism Details: Some evidence that increased BP some

how down regulates Na reabsorptionfrom the proximal tubule

Higher hydrostatic pressure in peritubularcapillaries reduces reabsorption fromthe proximal tubule. Pressure Natriuresis:

1) driven by simple hemodynamics 2) proximal nephron phenomenon 3) no sensors or circulating factors

Regulation of Na+ in Distal Nephron

Aldosterone: Most important “H20-independent” controller

of Na+ reabsorption & Na+ balance Steroid hormone produced by adrenal cortex

Acts on principle cells of the collecting duct

Circulating Angiotensin II stimulates its release

So… BP trigger baroreceptor response … this in turn triggers renin release … renin leads to increased angiotensin II levels … this triggers aldosterone release … this stimulates Na reabsorption … this leads to increased blood volume … increased blood volume leads to BP

This is summarized in the next figure.

Differential Hormonal Fine-Tuning

Collecting Duct

… BP triggers baroreceptor response … BP & sympathetic inputs trigger renin release from granular cells … renin enters circulation and leads to increased angiotensin II levels … angiotensin II triggers aldosterone release from adrenal cortex … aldosterone stimulates Na reabsorption from collecting duct … the retained Na leads to increased blood volume which raises BP

Aldosterone is not the only hormone that regulates the body’s Na+ balance.

Atrial Natriuretic Peptide

Atrial Natriuretic Peptide

released from heart when atria stretch due to high blood volume ( BP)

vasodilates afferent arteriole increasing GFR

inhibits Na reabsorption in from collecting duct

inhibits renin-angiotensin

Now….

Let’s look at hormonal control H20 balance

Regulation of H20 BalanceKey Hormone = Antidiuretic Hormone (ADH) sometimes called vasopressin

Collecting DuctADH :

Peptide hormoneCys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly

Released from posterior pituitary

Increases H20 Permeability of apicalmembrane by promoting the fusion

of vesicles containing an aquaporin

Input Signals that Control ADH Release1) cardiovascular baroreceptors

BP less baroreceptor firing ADH release BP more baroreceptor firing ADH release

2) hypothalamic osmoreceptors plasma osmolarity ADH release plasma osmolarity ADH release



2) hypothalamic osmoreceptors plasma osmolarity ADH release plasma osmolarity ADH release

Baroreceptors



2) hypothalmic osmoreceptors plasma osmolarity ADH release plasma osmolarity ADH release

Osmoreceptors

The cells thatrelease ADH integratethe 2 input signals.

“2 heads are better than 1”



2) hypothalmic osmoreceptors plasma osmolarity ADH release plasma osmolarity ADH release

Generally, osmolarity usually dominates unless there arevery large changes in volume.

Certain other brain level inputs can alter short-term ADH release (fear, pain, alcohol).

Diabetes insipidus is due to abnormal ADH regulation. Origin could be brain problem or bad renal ADH receptors.

Free Water Clearance (CH20)means to access renal H20 handling, not the usual clearance calculation

The CH20 determination considers urine as having 2 parts:UrineVolume

solute-free H20

H20 withsolute

Can be calculate as Osmolar Clearance

COSM =

UOSM · VPOSM

solute-free H20

H20 withsolute

This is the H20 “cleared”

Volume in which solutes present would be iso-osmotic compared to plasma.

v



solute-free H20

H20 withsolute


COSM =

UOSM · VPOSM

Thus…. CH20 = V - COSM

solute-free H20

H20 withsolute



v



solute-free H20

H20 withsolute


COSM =

UOSM · VPOSM


solute-free H20

H20 withsolute



v

Note: CH20 could be negative !! This is when veryconcentrated urine is being produced.



solute-free H20

H20 withsolute


COSM =

UOSM · VPOSM


If… V = COSM

Then… CH20

is zero

If… V < COSM

Then… CH20

is negative

solute-free H20

H20 withsolute



v

If… V > COSM

Then… CH20

is positive

Note: CH20 could be negative !! This is when veryconcentrated urine is being produced.

renal physiology origin of the hyperosmotic renal medulla

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