Renal Handling of Sodium and Water 2012

1. Renal Handling of Sodium and Water 2012 Syed Mohsin Raza, MD

2. Lecture Organization • Physiology of urinary concentration and dilution • Quantification of water excretion and TBW deficit/excess • Clinical disorders of concentration and dilution

3. Basic Concepts: Total Body Na Content • Na = Main cation in ECF • Size of ECF  Na content of the body • ECF volume depletion = decreased ECV • Total body Na deficit (and water) • Assessed by physical exam • Orthostatic hypotension, dry mucus membranes, … • ECF volume expansion = increased ECV • Total body Na excess • Assessed by physical exam • Edema, pleural effusion, pulmonary crackles, ascites, . . .

4. Basic Concepts: Total Body Water • Water: moves freely between ICF and ECF • Its movement is determined by osmotic and oncotic forces • ICFosmECFosmPosm • In most cases, • plasma osmolality 2X plasma Na • The serum [Na] reflects the relationship between total body Na and total body water • TBW excess  Low Posm Low plasma Na • TBW deficit  High Posm  High plasma Na

6. Calculated Plasma Osmolality Posm = 2 [Na] + [Glucose] + [BUN] Na, meq/ 18 2.8 glucose, mg/dL BUN, mg/dL

7. Artifactual Changes in Plasma [Na] • Hyperlipidemia • Hypergammaglobulinemia 150 mM 150 mM

8. Hyperosmolal Hyponatremia(Translocational Hyponatremia)

9. Hyperosmolal Hyponatremia(Pseudohyponatremia)

10. Hyperosmolal Hyponatremia(Pseudohyponatremia) New steady state

11. Approximation of Plasma Na after correction of Hyperglycemia • Add 1.6 meq/L to measured [Na] for each 100mg/dL glucose over 200mg/dL e.g. Na 130 meq/L Na 125 meq/L glucose 600 mg/dL glucose 1100 mg/dL Anticipated Na after treatment of hyperglycemia with insulin 4 x 1.6 = 6.4 9 x 1.6 = 14.4 130 + 6 = 136 meq/L 125 + 14 = 139 meq/L

12. Measurable Parameters in Na and Water Balance Na content ECF Volume Physical Findings High High Hypertension Edema Pulmonary crackles Ascites Low Low Hypotension Tachycardia Orthostasis

13. Parameters that can be Assessed in Na and Water Balance Na content (Mm) plasma [Na] = --------------- TBW

14. Examples • Person with edema, pulmonary crackles and pleural effusion: Total body Na content is HIGH • Lab values show plasma [Na] = 125 mM (low) Total body water content is HIGH relative to the Na content • Person with hypotension, dry mucous membranes: Total body Na content is LOW • Lab values show plasma [Na] = 125 mM (low) Total body water content is HIGH relative to the Na content

15. Examples • Person with hypotension and dry mucous membranes: Total body Na content is LOW • Lab values show plasma [Na] = 155 mM Total body water content is LOW relative to the Na content (this means TBW is REALLY low)

16. Extrarenal Determinants of Total Body Water

18. Thirst 2 to 3% increase in Posm THIRST decreased blood volume/pressure  THIRST

19. Basic Design for Water Balance Increased Water Decreased Water Water sensor

20. Basic Design for Water Balance Increased Water Decreased Water Water sensor Water Elimination Water Conservation Signal Signal

21. Basic Design for Water Balance Increased Water Decreased Water Water sensor Water Elimination Water Conservation Signal Signal Water Regulating Organ

22. Basic Design for Water Balance Increased Water Decreased Water Osmoreceptor ADH - ADH + Kidney Principal Cell of Collecting Duct

23. problem sensor thirst  plasma osmolality  osmoreceptor  magnocellular ADH neuron  ADH secretion  water reabsorption by the kidney  plasma osmolality restored signal effector water intake

24. Antidiuretic Hormone: Vasopressin • synthesized in magnocellular neurons • SON and PVN of hypothalamus • transported to vesicles in posterior pituitary • secreted in response to: 1. Increase in plasma osmolality 2. Decrease in blood volume/pressure 3. Activation by: chemoreceptors neurotransmitters

26. threshold Osmotic Control Volume/Pressure Control threshold = x-intercept sensitivity = slope

28. Control Sitesfor WaterMetabolism V2 V1a

29. Baroreceptors • Arterial: high pressure • aortic arch, carotid sinus • Volume/venous: low pressure: • atria, pulmonary vessels • Sensor - responds to stretch • Increased stretch  increased firing of nerves  inhibitADH • Decreased stretch decreased firing of nerves  stimulate ADH • Signal relayed via IX and X cranial nerves • to medulla  hypothalamus  ADH (vasopressin)

31. 15% increase volume/pressure

32. 15% decrease volume/pressure

33. BREAK HERE

34. Na+ (5%) Cortical Collecting Duct Na+ 20% Na+ Impermeable to water Permeable only if ADH present

35. Solute Reabsorption by TALH • Na,K ATPase on basolateral membrane KEY • impermeable to H2O • NaK2Cl transporter moves these solutes into the cell

36. Countercurrent Multiplier • descending limb of Henle • high water permeability • low solute permeability • thick ascending limb of Henle • water impermeable • active solute reabsorption • medullary interstitium • accumulation of solute removed from TALH • formation of interstitial gradient

38. Countercurrent Exchange • Vasa recta • high permeability to both solutes and H2O • provides nutrients and oxygen to medullary tubule segments • act as countercurrent exchangers

39. COUNTERCURRENT SYSTEM ALSO IS IN EFFECT IN THE PERITUBULAR CAPILLARIES.

40. Steepness of the Medullary Gradient • directly related to rate of solute reabsorption by TALH • inversely related to tubular fluid flow rate • inversely related to flow rate through the vasa recta

41. Urinary Dilution: Requirements 1. Normal GFR 2. Functioning TAL of Henle 3. Absence of ADH NOTE: In absence of ADH the collecting duct is IMPERMEABLE to water

42. Urinary Dilution NO ADH 50

43. Minimum ADH • no water reabsorbed in collecting tubule/duct • final urine flow is  20 mL/min ( 28.8 L/day) • minimal urine osmolality 50 - 100 mOsm/l

44. 600 mOsm of average daily solute can be eliminated by the kidneys in only 500cc of urine 600 mOsm of average daily solute require 12 liters of urine to be eliminated. WATER PLUG

45. CH2O : Free Water Clearance CH2O: Free Water Clearance CH2O = volume of urine that is solute free AFTER removal of the volume of urine that is iso-osmotic to plasma CH2O = V - Cosm

46. Clearance of Free Water • Clearance of free water: term used to describe solute free water in the final urine • It allows quantifying of the amount of water free of solute the kidney is excreting at a given time • Clearance of free water is that volume of urine that is solute free AFTER removal of the volume of urine that would be iso-osmotic to plasma

47. Causes of Impaired Urinary Dilution • decreased GFR • renal failure • low cardiac output • increased proximal TF reabsorption • heart failure • liver failure

48. Signs & Symptoms of Hypo-osmolalityHyponatremia = Low plasma [Na] • Headache • Nausea/vomiting • Confusion • Focal neurological signs • Seizures/coma • Death (brain herniation) All are signs of brain cells swelling in a confined space!

49. Urinary Concentration: Requirements 1. Normal GFR 2. Functioning TAL of Henle 3. Presence of ADH NOTE: In presence of ADH the collecting duct is PERMEABLE to water. Thus, fluid in the collecting duct will equilibrate with the medullary interstitium.

50. Maximum ADH • water is reabsorbed in late distal tubule/cortical collecting tubule • tubular fluid flow decreases from  20 mL/min to 6 mL/min by beginning of medullary collecting duct • water is reabsorbed by the medullary collecting duct under influence of ADH • tubular fluid osmolality can rise to 1200 mOsm/kg water • tubular fluid flow rate may fall as low as 0.35 mL/min (504 mL/day)