صدق الله العظيم الاسراء اية 58

By Dr. Abdel Aziz M. Hussein Lecturer of Medical Physiology

1) Osmoreceptors: Increase osmolarity by 1%  significant increase in ADH secretion. 2) Volume receptors: Decrease blood volume by 5-10%  increase ADH secretion via the baroreceptors in right atrium, carotid sinus and aortic arch.

1.At thick ALH → ++ Na +, K + & Cl - →↑ amount of solute reabs. 2.At CT and CCD → ↑ water permeability →↓ volume of H2O delivered to medulla from 15 ml to 5 ml → prevents irrigation of the medulla by water and loosing its high osmolarity. 3.At MCD →↑ water permeability →↑urea concentration → help urea reabsorption from PCD. 4.At PCD →↑ urea permeability → urea diffuse to the medulla increasing its osmolarity→ re-circulate between ALH and PCDs → entrapping of urea in the medulla Urea share by 50% of osmotically active particles in medullary osmolarity especially inner medulla (600 mosmol NaCl and 600 mosmol urea).

5. At vasa recta capillaries → ↓es medullary blood flow→ helps maintenance of medullary gradient, not dissipated (washed out) by high blood flow.

1.Aquaporin 1: present at the apical border of PT & DLH, not affected by ADH. 2.Aquaporin 2: present in the apical border of CD, specially principal cells. 3.Aquaporin 3: located at the basolateral border of principal cells to facilitate transport of urea & water. 4.Aquaporin 4: located in brain. 5.Aquaporin 5: located in salivary & lacrimal glands & respiratory system.

Diuresis means increased urine flow. Diuretics are substances used to produce diuresis.

Done by ingestion of large amount of water. Mechanisms: 1.Water load →↓ plasma osmolarity  →↓ ADH→↓ water permeability of the late DCT & CD → delivery of excess water to MCD. Absorption of this excess water → dilute the medulla→↓ solute concentration →↓magnitude of medullary gradient 2. Water load dilutes the plasma which: a.↑ the medullary blood flow. b.Creates ∆P for reabsorption of solutes in AVR → washout of medullary gradient.

Done by ingestion of large amount of non-absorbable solute. Mechanism Presence of non-absorbable solutes in the tubular fluid leads to: a) ↓ Na + & water reabsorption from PT : dilution of tubular Na + →↓ its concentration gradient. b) ↑ medullary blood flow → washout of the medullary gradient

Water diuresisOsmotic diuresis Produced by ingestion of large amount of water Produced by presence of large amount of non-absorbable solutes in tubular fluid as in: - Ingestion of mannitol. - Diabetes mellitus. Volume of urine: Up to 15% of GFR 17 ml/min Volume of urine can reach larger values due to inhibition of obligatory water reabsorption from PT Urine osmolarity: less due to ↑ed free water clearance Urine osmolarity: Higher than that of water diuresis but still hypotonic Free water clearance: wideFree water clearance: narrow Specific gravity: lessSpecific gravity: more Urinary Na + concentration: is less Urinary Na + concentration: is more

1.Diuretics that increase GFR as caffeine. 2.Diuretics that acts by inhibition of carbonic anhydrase enzyme as diamox  failure of reabsorption of NaHCO Loop diuretics: that block co- transport of Na + - K + - 2Cl at thick ALH as frusemide (lasix) which is a potent diuretic. 4.Thiazide diuretics: that block Na + - Cl - transport at the early DCT. 5.Diuretics that block Na + channels in principle cell as amiloride or compete with aldosterone on these cells as spironolactone. Both types of diuretics prevent Na + reabsorption in the principle cells. 6.Diuretic that block the action of ADH.

N.B. Of the above mentioned diuretics, amiloride and aldactone prevent K + loss in urine so, they are called K + -sparing diuretics while the other usually cause K + loss in urine and so, they are called K + - loosing diuretics.

1.Reabsorption of filtered HCO3. 2.Excretion of Fixed acids with formation of new HCO3 –Titratable acids –Ammonium ions.

1.Primarily in PT (90%) 2.Thick ALH and CDs (10%)

Due to more HCO 3 - reabsorption (90%) than water reabsorption (67%); HCO 3 - concentration is decreased and pH at the end of PT is 6.9.

Fixed acids are buffered by chemical buffers mainly HCO3 → so the pool of HCO 3 - is decreased. Example: Lactic acid + NaHCO 3 -  Na + lactate + H 2 CO 3  CO 2 + H 2 O CO 2 is eliminated by the lung. The amount of fixed acids per day 50 mmol/day So, the HCO3 pool decrease by 50 mmol/day Thus the kidney must form new HCO3 to replenish the lost HCO3 by fixed acids

Mechanism 1.Formation of new HCO3 with Excretion of Titratable acids 2.Formation of new HCO3 with Excretion of Ammonium ions

Titratable acidity is the portion of H bound to the filtered and excreted buffers. It equals the amount of alkali of NaOH added to urine to bring its pH back to 7.4. Or amount of H + secreted by renal tubules and utilized for buffering of filtered alkali, other than HCO 3 -. The filtered buffers are mainly phosphate and to some extent creatinine, urate and β-hydroxybutyrate.

In the CDs (fluid become HCO3 free), the secreted H combines with Na2 HPO4 (di-basic phosphate), to form NaH2Po4 (monobasic phosphate), the intracellular formed HCO3 is added to the blood. For each molecule of di-basic phosphate changed into monobasic phosphate, there is formation of one molecule of HCO3.

NH4 is the most important urinary buffer It is formed in the kidney from metabolism of Glutamine

Normally, the kidney excretes acids with NH3 as twice as the acid excreted as titratable acidity. In metabolic acidosis, the excretion of NH3 can ↑ up to 500 mEq/day, while the excretion of titratable acidity ↑es only to 50 mEq/day. In alkalosis, β intercalated cells secrete HCO3 instead of secretion of H

PTCDs Greater amount about 4000 mEq/day Less amount, 75 mEq/day Used for reabsorption of filtered HCO3 Used for generation of new HCO3 Secreted mainly by 2ry active mechanism in exchange with Na Secreted mainly by 1ry active transport by H-ATPase or H-K ATPase pH at the end of PCT is 6.9 due to leaky tight junctions PH at the end of CD is 4.6due to tight junction of the collecting ducts. Buffered by filtered HCO3 mainly. Buffered by either filtered phosphate or ammonia Aldosterone not affect itAffected by aldosterone

Hormone Stimulus for secretion Mechanism of actionEffects on the kidney PTH  plasma Ca 2+ Basolateral receptors  adenyl cyclase  cAMP  Ca 2+ reabsorption in DCT.  Phosphate reabsorption in PT. Stimulate 1 α hydroxylase on PT. ADH  Plasma osmolarity.  Blood volume. Basolateral V 2 receptors  cAMP  phosphorylation of aquaporin 2 (insertion of water channel at apical border).  Water permeability of the connecting tubules and CD. Aldosterone AgII. Hyperkalemia. New protein synthesis by transcription.  Na + reabsorption and K + secretion by the principle cell.  H + secretion by α- intercalated cell. Atrial Naturetic Peptide "ANP"  Atrial pressure. Stimulates guanyl cyclase enzyme  cGMP  GFR and decrease Na + reabsorption in DT. Angiotensin II (AII)  Na + - H + transporter which increase H + secretion and increase HCO 3 - reabsorption.

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