Daniel R. Kapusta, Ph.D. Department of Pharmacology, LSUHSC MEB Rm ; Urine Concentration and Dilution Regulation of Sodium and Water Balance
Urine Concentration and Dilution
AVP-dependent water permeability in the distal nephron
Aquaporin 2 – mediated water reabsorption in DCT
Countercurrent SYSTEM 1. Countercurrent flow: direction – anatomy 2. Countercurrent exchange: vasa recta 3. Countercurrent multiplication: tubules
1. Countercurrent FLOW DVR TAL tdloop AVR * Hairpin configuration - anatomical - loops of Henle (tubules) - vasa recta (capillaries) * Descending limbs close to ascending limbs * Fluid flow in opposite directions
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
3. Countercurrent MULTIPLIER Loops of Henle (tubules) * countercurrent multipliers - Pumping solute creates a large axial gradient - Establishes hyperosmotic medullary interstitial fluid ISF Osmotic gradient
Segmental renal tubular sodium reabsorption
Recycling of urea in the kidney
Renal handling of water in states of water diuresis
Renal handling of water in states of antidiuresis
Renal handling of water in states of water diuresis and antidiuresis
SIADH – Syndrome of inappropriate secretion of ADH Central diabetes insipidus Nephrogenic diabetes insipidus Vasopressin Pathologies
Regulation of Sodium and Water Balance
Distribution of Total Body Water (TBW)
Total Body Water Balance: Input = Output
Total Body Sodium Balance: Input = Output
Regulation of Arterial Blood Pressure BP = CO x TPR
Regulation of Arterial Blood Pressure BP = CO x TPR HR x SV
Regulation of Arterial Blood Pressure
Volume and Sodium/Osmole Sensors
Regulation of Arterial Blood Pressure: Closed loop system
Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Neural Control
Neural Control Mechanisms: Baroreceptors
Sympathetic control mechanisms regulating arterial blood pressure and sodium/water excretion
Renal sympathetic nerves and kidney function
Renal nerves contribute to segmental renal tubular sodium reabsorption
Renal nerves innervate the afferent renal arterioles: 1 receptor activation: renin release 1 adrenoceptor activation: vasoconstriction
Reduction in arterial blood volume activates the renal sympathetic nerves to enhance renal tubular sodium reabsorption
Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Humoral Control - Angiotensin II - Aldosterone - Atrial Natriuretic Peptide (ANP)
The renin-angiotensin-aldosterone system
Angiotensin II
Regulation of extracellular fluid volume
Angiotensin II and renovascular hypertension
Angiotensin and aldosterone enhance the renal tubular reabsorption of sodium U Na V
Chronic high salt diet reduces plasma renin (and Ang II) and increases plasma atrial natriuretic peptide levels High NaCl intake
Volume expansion: Integration of neural and humoral pathways to augment sodium and water excretion
Volume contraction: Integration of neural and humoral pathways to reduce sodium and water excretion
Deranged neural and humoral control in hypertension
Deranged neural and humoral control in congestive heart failure
Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Humoral Control AVP = ADH
Hypothalamic control of vasopressin (antidiuretic hormone) secretion
ADH secretion is more sensitive to changes in plasma osmolarity than to changes in blood volume
At plasma AVP levels that evoke thirst, water reabsorption and urine osmolality are already maximally increased
Central “osmoreceptors” and AVP secretion
Major Causes of Hyponatremia and Hypo-osmolality
Major Causes of Hypernatremia