Urine Concentration and Dilution

maintain the osmolality style Click to edit Master subtitleand volume of body fluids

3/12/13

Urine Concentration and Dilution Mechanisms

The kidneys maintain the osmolality and volume of body fluids within a narrow range by regulating the excretion of water and NaCl, respectively while producing either a concentrated or a diluted urine.

- When water intake is low or water loss increases, the kidneys conserve water by producing a small volume 3/12/13

Urine Concentration and Dilution Mechanisms

Involve: I. changes in the permeability of the loop of Henle to solutes and water that allow for the concentration and dilution of the tubular fluid,

Descending limbs of Henle's loop are concentrating segments: permeable to water, impermeable to reabsorption of solutes (urea can be secreted into the tubule, further concentrating the tubular fluid). Thick ascending limbs of Henle's loop are diluting segments: impermeable to water, but Na+-K+2Cl- transporters reabsorb electrolytes, thus 3/12/13 diluting the tubular fluid.

URINE CONCENTRATION AND DILUTION MECHANISMS I. CHANGES IN THE PERMEABILITY OF THE LOOP OF HENLE TO SOLUTES AND WATER

I. Fluid entering the descending thin limb of the loop of Henle from the proximal tubule is isosmotic with respect to plasma.

The descending thin limb is - highly permeable to water and

3/12/13

- much less

URINE CONCENTRATION AND DILUTION MECHANISMS CHANGES IN THE PERMEABILITY OF THE LOOP OF HENLE TO SOLUTES AND WATER The thin ascending limb of the loop of Henle is - impermeable to water but - permeable to NaCl. - as tubular fluid moves up NaCl is passively reabsorbed (concentration of NaCl in tubular fluid is higher than that in interstitial fluid). => the volume of tubular fluid remains unchanged along the length of the thin ascending 3/12/13

he distal tubule and the ortical portion of the ollecting duct are impermeable to urea.

URINE CONCENTRATION AND DILUTION MECHANISMS I. changes in the permeability of the loop of Henle to solutes and water

actively reabsorb NaCl and

are not permeable to water in e absence of ADH,

hen ADH is absent or present low levels (i.e., decreased asma osmolality), the molality of tubule fluid in these gments is reduced further 3/12/13

URINE CONCENTRATION AND DILUTION MECHANISMS I. changes in the permeability of the loop of Henle to solutes and water the kidneys excrete concentrated urine (antidiuresis) when plasma osmolality and plasma ADH levels are high

Fluid entering the descending thin limb of the loop of Henle from the proximal tubule is isosmotic with respect to plasma. descending thin limb

3/12/13 The

URINE CONCENTRATION AND DILUTION MECHANISMS I. changes in the permeability of the loop of Henle to solutes and water The thin ascending
limb of the loop of Henle is

- impermeable to water - permeable to NaCl. - as tubular fluid moves up the ascending limb, NaCl is passively reabsorbed because the concentration of NaCl in tubular fluid is higher than that in interstitial fluid. 3/12/13

URINE CONCENTRATION AND DILUTION MECHANISMS I. changes in the permeability of the loop of The thick Henle to solutes and water ascending limb of
the loop of Henle is - impermeable to water and urea. - permeable to NaCl which is actively reabsorbed from tubular fluid and thereby diluted; this segment is often referred to as the diluting segment of the kidney. Fluid leaving the thick ascending limb is hypoosmotic with respect to plasma (approximately 150 mOsm/kg H2O

the reabsorbed NaCl accumulates

3/12/13

the fluid reaching the collecting duct is hypoosmotic with respect to the surrounding interstitial fluid because of reabsorption of NaCl by the ascending limb of the loop of Henle, => an osmotic gradient is established across the collecting duct. In the presence of ADH, water diffuses out of the tubule lumen, and tubule fluid osmolality increases ( ADH increases the permeability of the last half of the 3/12/13 distal tubule and the collecting

URINE CONCENTRATION AND DILUTION MECHANISMS I. changes in the permeability of the loop of Henle to solutes and water

the medullary collecting duct, in the presence of ADH, increases its permeability to water; as water is reabsorbed osmolality of tubule fluid increases.

URINE CONCENTRATION AND DILUTION MECHANISMS I. changes in the permeability of the loop of Henle to solutes and water

Because cortical and outer medullary portions of the collecting duct are impermeable to urea, it remains in the tubular fluid, and its concentration increases. in the presence of ADH, the 3/12/13

Urine Concentration Mechanisms

The concentration gradient is established by (1) free water reabsorption from the descending limb of Henle, which increases the tubular fluid osmolarity in the descending limb (concentrating limb); (2) as more tubular fluid flows from the descending limb to the TALH, the more concentrated tubular fluid allows further transport of solutes into the interstitium; and (3) urea recycling contributes to the gradient, because it remains in the tubular fluid in the loop of Henle contributing to the tubular fluid osmolarity while water is reabsorbed from the descending limb, and when ADH is present, both water and urea reabsorption increases in the medullary collecting ducts (CDs), and the urea 3/12/13 is recycled to the inner medulla.

An of extracellular fluid, plasma osmolarity and pituitary ADH release is inhibited which makes less water be absorbed out of the tubular fluid in the descending limb,. the tubular fluid cannot be concentrated to as high a level, and there is increased tubular fluid flow to the TALH, which reduces the amount of solutes that can be transported into the interstitium disrupting the interstitial gradient. The decrease in ADH results in fewer water channels in the CDs, and less medullary water and urea reabsorption, =>increased production of hypotonic urine. When the excess fluid is 3/12/13 excreted, the plasma

Urine Dilution Mechanisms

URINE CONCENTRATION AND DILUTION MECHANISMS II. vasa recta

II. the ability of the kidneys to regulate overall water and solute reabsorption and and maintain the corticomedullary gradient is facilitated by : - the vasa recta that surround the medullary tubules and collecting ducts and by - the differences between the 3/12/13 cortex and medulla blood flow

URINE CONCENTRATION AND DILUTION MECHANISMS III. antidiuretic hormone

III. Antidiuretic hormone (ADH), or vasopressin, acts on the kidneys to regulate the volume and osmolality of urine. - When plasma ADH levels are low, a large volume of urine is excreted and the urine is dilute - When plasma levels are high, a small volume of urine is excreted, and the urine is concentrated. ADH is a small peptide synthesized in neuroendocrine cells located within the 3/12/13 supraoptic and paraventricular nuclei of the

URINE CONCENTRATION AND DILUTION MECHANISMS

When the effective osmolality of plasma increases, the osmoreceptors send signals to ADHsynthesizing/secreting cells located in the supraoptic and paraventricular nuclei of the hypothalamus, and synthesis and secretion of ADH are stimulated. is

when the effective 3/12/13 osmolality of plasma

URINE CONCENTRATION AND DILUTION MECHANISMS

A decrease in blood volume or pressure also stimulates secretion of ADH. The receptors responsible for this response are located in both the low-pressure (left atrium and large pulmonary vessels) and the high-pressure (aortic arch and carotid sinus) sides of the circulatory system. Because the low-pressure receptors are located in the high-compliance side of the circulatory system (i.e., venous) and because the majority of blood is in the venous side of the circulatory system, these low-pressure receptors can be viewed as responding to overall vascular volume. receptors respond to arterial

3/12/13 high-pressure The

URINE CONCENTRATION AND DILUTION MECHANISMS

Alterations in blood volume and pressure also affect the response to changes in body fluid osmolality With a decrease in blood volume or pressure, the set point is shifted to lower osmolality values when faced with circulatory collapse, the 3/12/13

3/12/13

3/12/13

kidneys and acid-base balance

Kidney help the body get rid of excess acid that accompanies food intake and metabolic reactions and replenish the HCO3- lost during neutralisation of nonvolatile acids Metabolism generates the largest potential source of acid as CO2 arising during oxidation of carbohidrates, fats, and most aminoacids is (15000 mmol/day)and 3/12/13

6. Kidney role in ABB

Renal function has a slow (hours-days) action, but is effective and determinant, because it achieves:

H+ secretion HCO3- reabsorption and synthesis Urinary buffers acidification (pH urinar= 4,58) NH4+ anhidrase excretion
carbonic

Into the nephrocytes from DT, TAS, CD key reaction :

3/12/13

CO2 + H2O

H2CO3

1. H+ secretion:

H+ production: 40-80 mM/day, eliminated into the urine as:

20-40 mM/day acid urinary buffers 30-40 mM/day - NH4+ (and the excess of H+)

Maintaining the [H+]pl (40 nEq/l) = essential for the good functioning of the enzymatic systems it corresponds to a blood pH =7,35-7,45 (extreme limits of the pH of 6,8 - 8)

Stimuli : - PCO2 - [H+] (Acidosis) 3/12/13 - Aldosterone.

Place of H+

secretion :

CPT: H+ secretion 80-90%:

mechanism: antiport H+/Na+ for each secreted H+ , 1 HCO3- is reabsorbed mechanism: antiport H+/Na+ for each secreted H+ , 1 HCO3- is reabsorbed

HL - TAS: H+ secretion 10%

DT (1/3 terminal) and CD: H+ secretion 10% the maximum urine acidification urinary pH =6 (limits between 4,5-8)

mechanism:

antiport H+/Na+ pump (intercalary cells)AT independent of

3/12/13 H+

2. HCO3

reabsorbtion:

[HCO3-]pl = 24-27 nEg/l important role in ABB at the renal level:

It is glomerulary filtrated (GF) if [HCO3-]pl 27 mEg/l:

It is reabsorbed at the tubular level 100% (Cl=0) HCO3- is produced into the nephrocyte from CO2 + H2O, in presence of CA

3/12/13

if [HCO3-]pl >27 mEg/l: HCO3- is

kidneys and acid-base balance Secreted H+ titrates HCO3-, filtered non-HCO3- buffers and endogenously produced NH3 I. Secreted H+ titrates HCO3,

Each day the glomeruli filter 180 l of blood plasma, each liter containing 24mmol of HCO3- so the daily filtered load of HCO3- is 180 liter x 24mM = 4320 mmol/day
3/12/13

If this filtered HCO3- would be lost in

kidneys and acid-base balance

Cellular mechanism for the reabsorption of filtered HCO3- by cells of the proximal tubule.

3/12/13

Cellular mechanisms for the reabsorption and secretion of HCO3- by intercalated cells of the collecting duct.

kidneys and acid-base balance Secreted H+ titrates HCO3-, filtered non-HCO3- buffers and endogenously produced NH3 II. Secreted H+ titrates filtered non-HCO3- buffers The titration of the non-HCO3- and non-NH3 buffers constitutes the titratable acid. The major proton acceptors of this 3/12/13 category are HPO42-, creatinine and to

kidneys and acid-base balance Secreted H+ titrates HCO3-, filtered non-HCO3- buffers and endogenously produced NH3 III. Secreted H+ titrates endogenously produced NH3 Most of the luminal NH3 is not the filtered one but the one diffused into the lumen from tubule cells while some NH4+ enter the lumen directly via the 3/12/13 apical Na-H exchanger.

kidneys and acid-base balance Production transport and excretion of NH4+

3/12/13

Physiology of urinary apparatus

Click to edit Master subtitle style Regulation of renal function. Functions of urine accumulation, retention and evacuation. Micturition.

3/12/13

1) Nervous regulation of renal activity

SNVS innervates: - smooth muscles from aa and ea - tubules Role: - RPF and GFR control - tubular function control Origin: T12 L2 Mediators: A and NA Receptors: NaCl and water elimination

Effects: - arteriolar vc GFR -RAAS Ag II - reabsorption of Na+ in renal tubules 2004 3/12/13 Dr. Carmen Bunu

2)Humoral regulation of renal activity

1. ADH 2. Aldosterone 3. RAAS 4. ANP

3/12/13

1. Role of ADH in renal activity regulation

ADH= antidiuretic hormone - synthesized in the anterior hypothalamus stored in the posterior hypophysis, where from it is released as needed effects:

1) Water reabsorption in distal tubule and the collecting duct 10% GFR

ADH water reabsorption diuresis with osmolarity ADH water reabsorption

3/12/13

Role of ADH in renal activity regulation

ADH stimulatory factors:

Plasma osmolarity:

plasma osmolarity ADH secretion water reabsorption plasma osmolarity of plasma volume ADH secretion water reabsorption plasma volume

Plasma volume:

Receptors:

3/12/13

Osmoreceptors in the anterior

Role of ADH in renal activity regulation

3/12/13

Baroreceptors in systemic circulation (carotid sinus, aortic arch) pulmonary circulation (LA, pulmonary veins) sense volemy variations (5-10%) volemy stimulation of baroreceptors in the small circulation ADH Mechanism: ADH binds to receptors (R) on the basal membrane of the nepfrocytes R-ADH complex activation of adenylate-cyclase intracellular AMPc stimulates the

Role of ADH in renal activity regulation

2) HL (TAS) - reabsorption of Na+, Cl3) Collecting duct:

urea reabsorption with a role in the counter-current multiplying mechanism reabsorption of water from CD [urea] from urine progressive reabsorption of urea (passive) cortico-papillar formation

3/12/13

2. Role of aldosterone in renal activity regulation

Aldosterone (ALD) = steroid hormone secreted by adrenal gland (cortex) Role: reabsorption of Na+ and elimination of K+ Action site: DT (2/3 terminal) and CD Mechanism:

ALD secretion is stimulated by

[Na+] pl [K+] pl

Renin-angiotensine system main role 3/12/13 2004 - activated by of volemy, BP, Dr. Carmen Bunu

2. Role of aldosterone in renal activity regulation

ALD passes in the nephrocyte it binds to an intra-cytoplasmatic receptor (R) complex R-ALD action on nuclear DNA RNA messenger synthesis, which transcripts the synthesis of specific proteins Main effects: at the apical pole of the nephrocyte: permeability to Na+ and K+ Na+ passes into the nephrocyte and K+ passes into the tubular lumen at the basal pole: it stimulates Na+/K+ ATP-ase in the basolateral membrane Na+ from nephrocyte 3/12/13

Bloo d Os
mV ol AD H

Recmembr . Adenylate cyclase ATP AMP c RecIC. DNA mRNA Pr synthesis Protei nkyn ase

Urine

H2O Kpl Na pl RAAS ALD

H2O Water channel (aquaporine 2) Na + K+ Mg2 Ca2+ + H+ NH4

Na K + + HCO3 -ClH2O
2004 3/12/13

Dr. Carmen Bunu

3.Role of RAAS in renal activity regulation

RAAS is a system connected with renal juxtaglomerular apparatus (JGA):

Renin is a proteolytic enzyme secreted by the cells of JGA (aa and ea granular cells) BP Volemy [Na+]pl

Factors stimulating renin synthesis:

urinary [Na+] to MD tubulo3/12/13 glomerular feedback

B V [Na SNV +] S ol P Angiote RENIN Angiote (10 AA, nn-sin I inactive) sinogen (inactive 2CONVERSION
hepatic globulin) ENZYME

Renin angiotensin aldosterone system

B P

[Na Ag II +] AN P 2004 3/12/13

Systemic: VC TPR Angiote Renal: VCae GFR = const n-sin II VCaa GFR Na+ reabsorption ANGIO- ALDO ADH TENSINASE water reabsorption S VC (more ) Angiote ALDO Na+ reabs. n-sin III Vol Dr. Carmen Bunu Cl-,

Effects of angiotensin II

Systemic: VC PVR BP Renal: VCea GFR = const water and VCaa GFR Na+ Na+ reabsorption elimination Aldosterone ADH water reabsorption Volemy

Effects of angiotensin III

less potent vasoconstrictor and water

2004 Aldosterone Na+Cl3/12/13 Dr. Carmen Bunu

Renin angiotensin aldosterone system

Conclusions:

RAAS controls BP Volemy [Na] renal irrigation control

JGA controls GFR through:

Baroreceptors in aa: pressure Renin pressure Renin Tubulo-glomerular feedback: Na to MD VDaa

3/12/13

4.Role of ANP in renal activity regulation

ANP = atrial natriuretic polypeptide secreted by atrial myocytes Role: excretion of urinary Na + diuresis Regulation: Stimulation: [Na+] pl., Ag II and volemy stimulation of baroreceptors in atrium release of ANP Inhibition: [Na+] pl. Effects: 3/12/13 GFR through:

Antagonist of RAAS Renin aldosterone secretion tubular reabsorption of Na+ and, secondarily, of Cl- and water urinary elimination of Na+

Global effect on the renal system diuretic and natriuretic (eliminates Na)

Other effects of ANP

on systemic vessels: vd through vascular + renal effect: BP

3/12/13

 Volemy Venous return Atrial baroRec ANP syste Renal mic VD re Kf nal VD RPF GFR

2004 3/12/13

Med ullar blood flow cortioc o papillar Reabs. water in Reabs. Dr. Carmen BunuCD water in

Renin Aldostero ne Reabs. Na+ in CD Natriuresi s ( Eliminati

2004 3/12/13

Dr. Carmen Bunu

Urine transport from kidneys to UB Urine transport: kidneys ureters

urinary bladder Urine is collected by collecting ducts papillae minor calyces major calyces renal pelvis ureter urinary bladder Urine formation process = continuous Urine evacuation process = discontinuous, by miction Ureters = muscular-elastic tubular formations structure: epithelium, muscular coat = smooth muscular fibers arranged in 3/12/13

Urine transport from kidneys to UB

Role: transports urine to the bladder, through peristaltic movements intraureteral pressure opening of the bladder entrance orifice passage of urine to the UB In the renal pelvis there are pacemaker cells (with automatism) action potential contraction

Important:

peristaltic type contraction begins forces the urine to enter the bladder contractions frequency: 1-8/min

3/12/13

Functions of urine accumulation, retention and evacuation. Micturition.

Effectuated by urinary bladder (UB); elimination of urine is done through the urethra. The two ureters converge to the urinary bladder. The bladder has body and neck: Structure: trilaminar muscular wall = detrusor formed of smooth muscle fibers arranged in all directions, which merge, forming areas with low electric resistance they conduct the action potential 3/12/13 rapidly

Bladder innervation: PNVS = pelvic nerves from sacred plexus origin in S2-S3, contain sensitive and motor fibers. extension receptors are located in the detrusor muscle = excited by bladder distension transmit stimuli to the medullar centers. role: detrusor contraction + internal sphincter relaxation micturition SNVS = hypogastric nerves most of them are originated in L2; contain sensitive and motor fibers. main effect on bladder vascularization reduced effect : detrusor relaxation + internal sphincter contraction role in the fullness sensation and 3/12/13 sometimes pain

Micturition/Urination

Urinary bladder accumulation and contention function

Urinary volume increases progressively urinary pressure increases, reaches a critical value of 15cm H2O

it corresponds to 100 ml of urine internal sphincter resistance limit.

The urine accumulates up to the pressure of 20 cm H2O

3/12/13

pressure corresponding to 400 ml of urine.

Micturition/Urination

Definition: medullar reflex act under voluntary inhibitor/facilitator cortical control. Obs: in newborns and children, miction is a purely reflex act

by mielinisation of nervous centers cortical control

Bladder filling miction contractions as a result of the extension reflex

3/12/13

initiated by the stimulation of extension receptors in the detrusor muscle (especially in the postero-inferior wall)

Micturition/Urination

Once the micturition reflex is initiated, it autogenerates initial bladder contraction activates more and more extension receptors bladder contraction.

Process duration = seconds1 min, then progressively decreases allows bladder relaxation. Miction reflex comprises:

progressive and rapid increase of detrusor muscle pressure considerable period of increased

3/12/13

Micturition/Urination

If the bladder is not emptied when the micturition reflex occurs the reflex is inhibited for a period of minutes 1 hour, when a new reflex occurs, stronger and more frequent. If the bladder is just partly filled the detrusor muscle relaxes spontaneously.

Importance of cortical control:

3/12/13

superior nerve centers determine micturition reflex inhibition most of the time

Micturition control
Distension receptors Afferent path Centers Efferent path Effectors Result

SNVS

In the vesical HypogaL2 Hypoga- Detrusor muscle detrusor stric nerves (majority) stric nerves relaxation muscle Int. sphincter contraction

Opposes to micturition reflex

PSNV

In the vesical detrusor muscle

Pelvic nerves

S2 S3

Pelvic nerves

Detrusor muscle contraction Int. sphincter relaxation

Micturition reflex

Voluntary control

In the vesical Pudendal Superior Pudendal External sphincter detrusor nerves + nerve centers nerves relaxation muscle spyno(pons + thalamic External sphincter cortex) contraction tract

Voluntary micturition Opposes to micturition

2004 3/12/13

Dr. Carmen Bunu

Pelvic nerves (SNVP) + Hypogastric n. + (SNVS) Pudendal nerves voluntary control

2004 3/12/13 Dr. Carmen Bunu

Detrusor muscle

Internal - sphincter External sphincter