1. Overview of the Maintenance of Water and Ions Kidneys Baroreceptors Osmoreceptors

2. Generation of a high interstitial osmolality 300 Starting point 400 200 2. Equilibration of osmolality between descending limb and Interstitium 200 400 300 400 200 3. Shifting fluid along loop Cycle 2 300 400 500300 200400 350150 400 200 500 350 400 350 400 150 200 300 200 300 500 400 300 350 200 150 after a few cycles 300 500 700 1000 800 100 10001200 300 400 200 1. Generation of 200 mOsm gradient Cycle 1

3. Osmolality (mOsm/l) 300 500 700 900 1100 300 500 700 900 1100 300 500 700 900 100 300 500 700 900 1100 ADH Blood Movement of: Salt Water ADH Anti Diuretic hormone ADH

4. Osmolality (mOsm/l) 300 500 700 900 1100 300 500 700 900 1100 300 500 700 900 100 Blood Movement of: Salt Water 100 ADH Anti diuretic hormone 90 80 70 65 ADH

5. Diuresis and Antidiuresis max. antidiuresis max. water diuresis Max. antidiuresis : V U = 0,3 ml·min -1 Max. diuresis : V U = 16 ml·min -1 Normal : V U = 1 ml·min -1 100 80 60 40 20 0 35 % 20 % Proximal Late distal and Collecting duct H 2 O (% of GFR) Under control of ADH }

6. Osmolality of tubular fluid (effect of ADH) Proximal tubule Thin loop Distal tubuleCollecting ductUrine 1200 1000 800 600 400 200 0 Osmolality (mOsm/l) diluting segment late distal ADH effect without ADH with ADH

7. Normal values Renal Blood flow RBF = 1100 ml·min -1 with hematocrit, Hct = 45% Effective Renal Plasma flow ERPF = 600 ml·min -1 Urine flow (V): 1 ml·min -1 = 1,5 L·day -1 minimal value 0,3 ml·min -1 by extreme dehydratation maximal value 16 ml·min -1 by extreme water intake; average value

8. GFR = 120 ml·min -1 M = GFR · P Diuresis: V = 16 ml·min -1 120 16  7,5 times concentrated Antidiuresis: V = 0,3 ml·min -1  400 times concentrated 120 0,3 M = V · U Concentrating of substances in Urine example: (Inulin) H2OH2O ( ) U P Inulin is a measure for H 2 O reabsorption ! GFR V =

9. Ability of urine concentration Maximal concentration (mOsm) Urine / Plasma ratio Beaver Pig Human White rat Kangaroo rat Desert spring mouse 520 1100 1400 3000 5500 9400 2 4 5 10 14 25 Schmidt-Nielsen, 1979

10. Effects of ADH Tubular fluid Cell Blood R ADH C A H2OH2O H2OH2O ATP cAMP Protein kinase Phosphoproteins

11. Stimuli releasing ADH A: Osmolality 270 280290310300 Plasma osmolality (mOsm/kg H 2 O) Max 0 Plasma [ADH] B: Blood volume -30 -20 -10 010 20 Max 0 Changes in blood volume or blood pressure ( %)

12. ADH effects on urine osmolality and urine excretion rate Urine excretion rate Total excretion of electrolytes Urinosmolality 0Plasma ADH Max Min

13. ADH (= Antidiuretic hormone = vasopressin) Synthesis: Ncl. supraopticus and paraventricularis (Hypothalamus) Storing : Neurohypophysis ADH deficiency: Diabetic insipidus Releasing stimuli : Osmoreceptors (III. Ventricle) : OsmolarityADH Stretch receptors in low pressure system (right atrium) : Pressure ADH