Daniel R Kapusta Ph D Department of Pharmacology

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

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 * Hairpin configuration anatomical - loops of Henle (tubules) - vasa recta (capillaries) * Descending limbs close to ascending limbs * Fluid flow in opposite directions DVR tdloop TAL AVR

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

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

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

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 UNa. V

Chronic high salt diet reduces plasma renin (and Ang II) and increases plasma atrial natriuretic peptide levels High Na. Cl 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