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Daniel R. Kapusta, Ph.D. Department of Pharmacology, LSUHSC MEB Rm 7106

Daniel R. Kapusta, Ph.D. Department of Pharmacology, LSUHSC MEB Rm 7106 568-3940; dkapus@lsuhsc.edu. Urine Concentration and Dilution Regulation of Sodium and Water Balance. Urine Concentration and Dilution. AVP-dependent water permeability in the distal nephron.

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Daniel R. Kapusta, Ph.D. Department of Pharmacology, LSUHSC MEB Rm 7106

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  1. Daniel R. Kapusta, Ph.D. Department of Pharmacology, LSUHSC MEB Rm 7106 568-3940; dkapus@lsuhsc.edu Urine Concentration and Dilution Regulation of Sodium and Water Balance

  2. Urine Concentration and Dilution

  3. AVP-dependent water permeability in the distal nephron

  4. Aquaporin 2 – mediated water reabsorption in DCT

  5. Countercurrent SYSTEM • 1. Countercurrent flow: • direction – anatomy • 2. Countercurrent exchange: • vasa recta • 3. Countercurrent multiplication:tubules

  6. 1. Countercurrent FLOW • * Hairpin configuration - anatomical - loops of Henle (tubules) - vasa recta (capillaries) • * Descending limbs close to ascending limbs • * Fluid flow in opposite directions  TAL  DVR  tdloop  AVR

  7. 2. Countercurrent EXCHANGER • * Vasa recta (capillaries) - Countercurrent exchangers - Passive process depends on diffusion of solutes & water in both directions across permeable walls of the vasa recta

  8. 3. Countercurrent MULTIPLIER • Loops of Henle (tubules) • * countercurrent multipliers • - Pumping solute creates a large • axial gradient • - Establishes hyperosmotic • medullary interstitial fluid ISF Osmotic gradient

  9. Segmental renal tubular sodium reabsorption

  10. Recycling of urea in the kidney

  11. Renal handling of water in states of water diuresis

  12. Renal handling of water in states of antidiuresis

  13. Renal handling of water in states of water diuresis and antidiuresis

  14. Vasopressin Pathologies SIADH – Syndrome of inappropriate secretion of ADH Central diabetes insipidus Nephrogenic diabetes insipidus

  15. Regulation of Sodium and Water Balance

  16. Distribution of Total Body Water (TBW)

  17. Total Body Water Balance: Input = Output

  18. Total Body Sodium Balance: Input = Output

  19. Regulation of Arterial Blood Pressure BP = CO x TPR

  20. Regulation of Arterial Blood Pressure BP = CO x TPR HR x SV

  21. Regulation of Arterial Blood Pressure

  22. Volume and Sodium/Osmole Sensors

  23. Volume and Sodium/Osmole Sensors

  24. Regulation of Arterial Blood Pressure: Closed loop system

  25. Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Neural Control

  26. Neural Control Mechanisms: Baroreceptors

  27. Sympathetic control mechanisms regulating arterial blood pressure and sodium/water excretion

  28. Renal sympathetic nerves and kidney function

  29. Renal nerves contribute to segmental renal tubular sodium reabsorption

  30. Renal nerves innervate the afferent renal arterioles: 1 receptor activation: renin release 1 adrenoceptor activation: vasoconstriction

  31. Reduction in arterial blood volume activates the renal sympathetic nerves to enhance renal tubular sodium reabsorption

  32. Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Humoral Control - Angiotensin II - Aldosterone - Atrial Natriuretic Peptide (ANP)

  33. The renin-angiotensin-aldosterone system

  34. Angiotensin II

  35. Regulation of extracellular fluid volume

  36. Angiotensin II and renovascular hypertension

  37. Angiotensin and aldosterone enhance the renal tubular reabsorption of sodium  UNaV

  38. Chronic high salt diet reduces plasma renin (and Ang II) and increases plasma atrial natriuretic peptide levels High NaCl intake

  39. Volume expansion: Integration of neural and humoral pathways to augment sodium and water excretion

  40. Volume contraction: Integration of neural and humoral pathways to reduce sodium and water excretion

  41. Deranged neural and humoral control in hypertension

  42. Deranged neural and humoral control in congestive heart failure

  43. Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Humoral Control AVP = ADH

  44. Hypothalamic control of vasopressin (antidiuretic hormone) secretion

  45. ADH secretion is more sensitive to changes in plasma osmolarity than to changes in blood volume

  46. At plasma AVP levels that evoke thirst, water reabsorption and urine osmolality are already maximally increased

  47. Central “osmoreceptors” and AVP secretion

  48. Major Causes of Hyponatremia and Hypo-osmolality

  49. Major Causes of Hypernatremia

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