renal system 3 Presentation

Urine Concentration and Dilution

maintain the osmolality and volume of body fluids

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 hyperosmotic urine.

- When water intake is high, a large volume of hypoosmotic urine is produced.

• In a normal individual, urine osmolality (Uosm) can vary from approximately 50 to 1200 mOsm/kg H2O)and the corresponding urine volume can vary from approximately 18 to 0.5 L/day.

• the kidneys control water excretion independently of their ability to control the excretion of various other physiologically important substances such as Na+ K+ and ureea.

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 diluting the tubular fluid.

II. vasa recta as part of the ability of the kidneys to regulate overall water and solute reabsorption ( they surround the medullary tubules and collecting ducts).

III. the fine-tuning to concentrate urine in the collecting ducts because of antidiuretic hormone (ADH)-sensitive water channels that allow solute-free water reabsorption and concentration of the hypo-osmotic tubular fluid.

URINE CONCENTRATION AND DILUTION MECHANISMSI. 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 - much less permeable to solutes such as NaCl and

urea. • as the fluid in thin limb descends deeper into the

hyperosmotic medulla, water is reabsorbed (via AQP1) because of the osmotic gradient set up by both NaCl and urea, present at high concentrations in the medullary interstitium

• at the bend of the loop tubular fluid osmolality = surrounding interstitial fluid

osmolality. • Although the osmolality is similar at the bend of the

loop, their compositions differ: tubular fluid [NaCl] > interstitial fluid [NaCl] tubular fluid [ureea] < interstitial fluid [ureea].

URINE CONCENTRATION AND DILUTION MECHANISMSCHANGES 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 limb, but the concentration of NaCl decreases (tubular fluid dilution begins).

• The thick ascending limb of the loop of Henle is - impermeable to water and urea. - actively reabsorbs NaCl from tubular fluid and thereby dilutes

it. - Dilution occurs to such a degree that 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).

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

water

The distal tubule and the cortical portion of the collecting duct

- actively reabsorb NaCl and - are impermeable to urea. - are not permeable to water in the absence of

ADH, when ADH is absent or present at low levels (i.e.,

decreased plasma osmolality), the osmolality of tubule fluid in these segments is reduced further because NaCl is reabsorbed without water; fluid leaving the cortical portion of the collecting duct is hypoosmotic with respect to plasma (approx. 50 to 100 mOsm/kg H2O)

The medullary collecting duct - actively reabsorbs NaCl. - is slightly permeable to water and urea even in

the absence of ADH; some urea enters the collecting duct from the medullary interstitium, and a small volume of water is reabsorbed.


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.

• The descending thin limb is - highly permeable to water and - much less permeable to solutes such as NaCl and urea. • as the fluid in thin limb descends deeper into the

hyperosmotic medulla, water is reabsorbed (via AQP1) because of the osmotic gradient set up by both NaCl and urea, present at high concentrations in the medullary interstitium

• at the bend of the loop tubular fluid osmolality = surrounding interstitial fluid

osmolality. • Although the osmolality is similar at the bend of the loop,

their compositions differ: tubular fluid [NaCl] > interstitial fluid [NaCl] tubular fluid [ureea] < interstitial fluid [ureea].


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.

=> the volume of tubular fluid remains unchanged along the length of the thin ascending limb, but the concentration of NaCl decreases.

=> as fluid ascends through the thin ascending limb, it becomes less concentrated than the surrounding interstitial fluid (i.e., tubular fluid dilution begins).


water • The thick 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 in the medullary interstitium and raises its osmolality providing the osmotic driving force for reabsorption of water by the medullary collecting duct, crucial for the production of hyperosmotic urine.

• The overall process by which the loop of Henle, in particular, the thick ascending limb, generates the hyperosmotic medullary interstitial gradient is termed countercurrent multiplication

• ADH stimulates reabsorption of NaCl by the thick ascending limb of Henle's loop. This is thought to maintain the medullary interstitial gradient at a time when water is being added to this compartment from the medullary collecting duct, which would tend to dissipate the gradient.


water

• 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 distal tubule and the collecting duct to water).

• This diffusion of water out of the lumen of the collecting duct begins the process of urine concentration.

• The maximum osmolality that the fluid in the distal tubule and cortical portion of the collecting duct can attain is approximately 290 mOsm/kg H2O = the osmolality of the interstitial fluid and plasma within the cortex of the kidney.

• the fluid at this point has the same osmolality as the fluid that entered the descending thin limb, but its composition was changed; NaCl accounts for a much smaller proportion of total tubular fluid, because of its reabsorption by the preceding nephron segments. Tubule fluid osmolality reflects the presence of urea (filtered urea plus urea added to the descending thin limb of the loop of Henle) and other solutes (e.g., K+, NH4+, creatinine)


water

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

• 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 permeability of the inner medullary collecting duct to urea is increased.

• Because the concentration of urea in the tubular fluid has been increased by reabsorption of water in the cortex and outer medulla, its concentration in tubular fluid is greater than its concentration in interstitial fluid, and some urea diffuses out of the tubule lumen into the medullary interstitium.

• The maximal osmolality that the fluid in the medullary collecting duct can attain is equal to that of the surrounding interstitial fluid.

• The major components of the tubular fluid within the medullary collecting ducts are substances that have either escaped reabsorption or have been secreted into the tubular fluid. Of these, urea is the most abundant.

Urine Concentration MechanismsThe 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 is recycled to the inner medulla.(4)transport of solutes, but not water, out of the thick ascending limb of Henle (TALH) via the Na+-K+-2Cl- transporters (diluting limb);

Urine Dilution Mechanisms•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 excreted, the plasma osmolarity will increase, stimulating ADH, and the interstitial concentration gradient will be reestablished over several hours.

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 cortex and medulla blood flow - blood flow through

the medulla is relatively low, no more than 5-10 % of total renal flow ment to minimize the washout of the medullary hypertonicity; .

The hearpin configuration of vasa recta with descending and ascendig components, both entering and leaving through the same region maintain the osmotic stratification in the medullary interstitium

Osmotic stratification from cortex to papilla is due to a gradient of [Na] , [Cl] and [ureea];

- blood of decending vasa enters the hiperosmotic milieu of the medula and looses its water to the hiperosmotic environment while receving NaCl and urea that difuse into the lumen of decending vasa recta resultig an increase in blood osmolarity while approaching the tip of the hair pin.

- As blood travels in the ascending vasa recta towards the cortex it has a higher solutes concentration and water moves from the interstitium in the lumen while solutes diffuse from the lumen in the interstitium.

- Solutes recirculate from the ascending vessel to the descending vessel through interstitium and water from the descending vessel to the ascending one trapping the solutes inside the medulla and maintaining corticomedullary gradient

Vasa recta carries away the excess of ureea , NaCl and water because its ascending part carries out more salt and water than its descending part carry in .

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 supraoptic and

paraventricular nuclei of the hypothalamus. ADH is packaged in granules that are transported down the axon of the cell and stored in nerve terminals located in the neurohypophysis.

The two primary physiological regulators of ADH secretion are - the osmolality of the body fluids (osmotic) and -the volume and pressure of the vascular system (hemodynamic). Other factors include : - nausea (stimulates) - angiotensin II (stimulates) - atrial natriuretic peptide (inhibits) - nicotine stimulates secretion, - ethanol inhibits secretion.

URINE CONCENTRATION AND DILUTION MECHANISMS

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

• when the effective osmolality of plasma is reduced, secretion is inhibited. Because ADH is rapidly degraded in plasma, circulating levels can be reduced to zero within minutes after secretion is inhibited.

• The set point of the system is the plasma osmolality value at which ADH secretion begins to increase. Below this set point, virtually no ADH is released. The set point varies among individuals and is genetically determined. In healthy adults, it varies from 275 to 290 mOsm/kg H2O

• Several factors can also change the set point in a given individual: alterations in blood volume and pressure can shift it, pregnancy is associated with a decrease in the set point.


• 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.

• The high-pressure receptors respond to arterial pressure. • Both groups of receptors are sensitive to stretch of the wall of the structure in which they are

located • Signals from these receptors are carried in afferent fibers of the vagus and glossopharyngeal

nerves to the brainstem (solitary tract nucleus of the medulla oblongata), which is part of the center that regulates heart rate and blood pressure Signals are then relayed from the brainstem to the ADH-secreting cells of the supraoptic and paraventricular hypothalamic nuclei.

• The sensitivity of the baroreceptor system is less than that of the osmoreceptors, and a 5% to 10% decrease in blood volume or pressure is required before ADH secretion is stimulated


• 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 kidneys will continue to conserve water, even though by doing so they reduce the osmolality of body fluids. With an increase in blood volume or pressure, the opposite occurs.

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 the lungs excrete this large amount by diffusion along the respiratory membrane.

• Metabolism also generates nonvolatile acids (sulfuric, phosphoric, organic acids) and nonvolatile bases which leaves a net endogenous H+ production of 40mmole/day for a 70 kg person

• The diet might add 20 mmole/ day of H+ and considering the 10 mmole/day loos of bases in stool, the total load of nonvolatile acids represents about 1 mmol/Kg body (70mmole/day)

• Kidney handle this acid load excreting approx. 70mmol/day of H+ (30 mmol tritatable acid/day and 40 mmole NH4+/day) into urine and simultaneously transporting 70mmol/day of new HCO3- into the blood

• Generation of new HCO3- is achived by the excretion of titratable acids and by the synthesis and excretion of NH4+

6. Kidney role in ABBRenal 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= 4,5-8)– NH4

+ excretion• Into the nephrocytes from DT, TAS, CD – key reaction :

CO2 + H2O H2CO3 HCO3- + H+

Cellular metabolism, (reabsorbed)(secreted)Tubular fluid, blood• Into the intercalary cells from CD: H+ excretion through

the H+ pump

carbonic

anhidrase

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) - Aldosterone.

• Place of H+ secretion :– CPT: H+ secretion 80-90%: • mechanism: antiport H+/Na+

• for each secreted H+ , 1 HCO3- is reabsorbed

– HL - TAS: H+ secretion 10%• mechanism: antiport H+/Na+

• for each secreted H+ , 1 HCO3- is reabsorbed

– 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+

– H+ pump (intercalary cells)AT independent of Na+

• For each secreted H+ , 1 HCO3- is reabsorbed.

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

– if [HCO3-]pl >27 mEg/l: HCO3

- is eliminated into urine


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• If this filtered HCO3- would be lost in urine the result is a blood acid load of

4320mmol/day• The kidney by secreting H+ into the tubule lumen titrate the filtered HCO3- to CO2

and H2O. • CO2 produced in the lumen and H2O diffuses into the tubule cells and regenerate

intracellular H+ and HCO3- in the presence of intracellular carbonic anhidrase. • Cells export the H+ out across the apical membrane into the lumen tubule and the

HCO3- out across the basolateral membrane into the blood.• The 4320 mmole of HCO3- requires 4320 mmole of H+ secretion every day far more

than the 70 mmole/day of H+ secretion used for neutralising nonvolatile acids


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

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


Secreted H+ titrates HCO3-, filtered non-HCO3- buffers and endogenously produced NH3

II. Secreted H+ titrates filtered non-HCO3- buffersThe titration of the non-HCO3

- and non-NH3 buffers constitutes the “titratable acid”.

The major proton acceptors of this category are HPO42-,

creatinine and to a lesser extent urate and other buffers.For each H+ transferred to the lumen to titrateone new

HCO3- is generated in the tubule cell and transferred to the blood


Secreted H+ titrates HCO3-, filtered non-HCO3- buffers and endogenously produced NH3III. Secreted H+ titrates endogenously produced NH3Most 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 apical Na-H exchanger.NH4+ is produced in the cells of the proximal tubule from glutamine. Each glutamine

molecule produces two molecules of NH4 and 2-oxoglutarate 2- whose metabolism provides 2 HCO3

- .

HCO3- exits the cell across the basolateral membrane intering the peritubular capilaries as new

HCO3-NH4+exit the cell via the apical membrane and enters the tubular fluid because of Na-H

antiporter where H+ is substituted by NH4+. In adition NH3 diffuse out of the cell across plasma membrane being protonated inside the tubular fluid.

An important part of the secreted NH4+ in the proximal tubule will be reabsorbed in the ascending thick loop of Henle and accumulates in the medullary interstitium. From the medulary interstitium NH3 will be secreted by the collecting duct cells into the tubular lumen where it is protonated and eliminated through urine . A second mechanism involves NH4+-H+ antiporters in both basolateral and apical membranes of the collecting ducts cells

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

Physiology of urinary apparatus

Regulation of renal function.Functions of urine accumulation, retention

and evacuation. Micturition.

Dr. Carmen Bunu2004

• 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: a• Effects: - arteriolar vc GFR

-RAAS Ag II - reabsorption of Na+ in renal tubules

• Stimulation: BP, plasma volume• Result: BP, plasma volume

1) Nervous regulation of renal activity

NaCl and water elimination

2)Humoral regulation of renal activity

1. ADH2. Aldosterone3. RAAS4. ANP

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 diuresis with osmolarity

Role of ADH in renal activity regulation

– ADH stimulatory factors:• Plasma osmolarity:– plasma osmolarity ADH secretion water

reabsorption plasma osmolarity • Plasma volume:– of plasma volume ADH secretion water

reabsorption plasma volume– Receptors:• Osmoreceptors in the anterior hypothalamus–They sense small variations of plasma osmolarity

(=“osmometers”)– osmolarity receptors stimulation (shrinkage) ADH

Role of ADH in renal activity regulation• 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 proteinkinases membrane permeability at the apical pole: opens water channels water reabsorption (ADH-dependent water “facultative reabsorption” = 15% GFR)

• ADH urine volume (0.5 l/day) with osmolarity (1200mOsm/l)• ADH urine volume (10% of water is not

reabsorbed) with osmolarity diabetes insipidus

Role of ADH in renal activity regulation

2) HL (TAS) - reabsorption of Na+, Cl-

3) 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) D cortico-papillar formation

Dr. Carmen Bunu2004

• 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

- activated by of volemy, BP, [Na+]pl or [Na+]urin on MD SNVS stimulation

2. Role of aldosterone in renal activity regulation

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 blood, and K+ from blood nephrocyte urine

• Associated effects:–Reabsorbs Cl- and HCO3

- passively, and water secondarily–Eliminates K+, Mg2+, Ca2+, NH4

+, H+ urine acidification.

Dr. Carmen Bunu2004

BloodUrine

H2OWater channel (aquaporine 2)

ATP

DNA mRNA

Pr synthesis

NH4+

Na+

ADHRecmembr.

Adenylate cyclase

AMPc

Proteinkynase

H2O

ALD RecIC.

K+Na+

K+

HCO3-

Cl-

H2O

Mg2+

Ca2+

H+

OsmVol

Kpl

Napl

RAAS

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) • Factors stimulating renin synthesis:– BP– Volemy– [Na+]pl– urinary [Na+] to MD tubulo-glomerular feedback– SNVS stimulation

• Factors inhibiting renin synthesis:– Aldosterone [Na+]pl (negative feedback)– ANP

Dr. Carmen Bunu2004

Renin angiotensin aldosterone system

Angioten-sinogen

Angioten-sin I

Angioten-sin II

Angioten-sin III

(inactive a2- hepatic globulin)

(10 AA, inactive)RENIN

CONVERSION ENZYME

ANGIO-TENSINASES

BP Vol [Na+] SNVS

Systemic: VC TPRRenal: VCae GFR = const VCaa GFR Na+ reabsorption ALDOADH water reabsorption

VC (more ) ALDO Na+ reabs. Cl-, water VolANP

BP [Na+] AgII

--

Dr. Carmen Bunu2004

• Effects of angiotensin II– Systemic: VC PVR BP– Renal: VCea GFR = const

VCaa GFRNa+ reabsorption

– Aldosterone – ADH water reabsorption

• Effects of angiotensin III– less potent vasoconstrictor– Aldosterone Na+Cl- and water reabsorption

water and Na+

elimination

Volemy

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

VCea (by Renin)

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:– GFR through:• vd on afferent arteriole and vc on efferent arteriole,• Kf

– RPF in medullar zone D cortico-papillar water reabsorption in CD

– 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– neurotransmitter

Dr. Carmen Bunu2004

Volemy

Venous return

Atrial baroRec

ANP

systemic VD

Renal

renal VD

RPF

GFR

Kf Medullarblood flow

Renin

Aldosterone

cortioco-papillar

Reabs. water in CD

Reabs. Na+ in CD

Natriuresis ( Elimination of Na+ through urine)

Reabs. water in CD

Dr. Carmen Bunu2004

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 three layers; – inervation: SNVS (-), PSNV (+), intramural nervous

plexus;– They open obliquely on the postero-inferior wall of UB,

with a part that passes through the bladder wall contraction of detrusor muscle compresses the ureter, obstructing the vesico-ureteral reflux.

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

• Important:– In the renal pelvis there are pacemaker cells (with automatism)

action potential contraction• peristaltic type contraction begins forces the urine to enter

the bladder• contractions frequency: 1-8/min • urinary volume in the tube detention of the tube

automatism through miogenic mechanism– The tonus and the peristaltism are under the control of VNS

• SNS (hypogastric n.): tonus + peristaltism• PSNS (vagus n.): tonus + peristaltism

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 rapidly

– The bladder neck has two sphincters:• Internal sphincter (smooth muscle) under

+ SNVS - SNVP control

• External sphincter (striated muscle) under voluntary control.

• 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 sometimes pain

– Cortical control - with centers in the pons + cortex• afference from spino-thalamic tract• efference through pudendal nerves to the external

sphincter (+/-)

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 • pressure corresponding to 400 ml of urine.

– Rhythmic contractions for miction occur, but the control of external sphincter prevent the miction.

– The urine accumulates up to the pressure of 70 cm H2O (external sphincter resistance limit.)

• Normally in the bladder 500-600 ml of urine without painful distension is accumulated.– UB adapts its tonus to the content.

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– initiated by the stimulation of extension receptors in

the detrusor muscle (especially in the postero-inferior wall)

– afferent path: pelvic nerves– S2–S3 centers– efferent path: pelvic nerves– effectors: detrusor muscle contraction

internal sphincter relaxation

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 pressure– return to the basal tonus.

• When miction reflex is strong enough pudendal nerves stimulation external sphincter relaxation– by voluntary control: external sph. relax. micturition

ext. sph. contr. delayed micturition.

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:

• superior nerve centers determine micturition reflex inhibition most of the time

• even though reflex occurs, sustained contraction of the external sphincter opposes to micturition until a convenient moment

• if the micturition is consented, cortical centers facilitate sacred PSNV centers + external sphincter relaxation

Dr. Carmen Bunu2004

Distension receptors

Afferent path

Centers Efferent path

Effectors Result

SNVS In the vesical detrusor muscle

Hypoga-stric

nerves

L2

(majority)

Hypoga-stric

nerves

Detrusor muscle relaxation

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

Volun-tary control

In the vesical detrusor muscle

Pudendal nerves +spyno-

thalamic tract

Superior nerve

centers(pons + cortex)

Pudendal nerves

External sphincter relaxation

External sphincter contraction

Voluntary micturition

Opposes to micturition

Micturition control

Dr. Carmen Bunu2004

+

+

-

-

Pelvic nerves(SNVP)

Hypogastric n.(SNVS) Internal

sphincter

Externalsphincter

Detrusor muscle

Pudendal nerves

voluntary control

Documents

renal system 3 Presentation