Electrolyte and Water Homeostatis Notes

Sodium (Water) Potassium Calcium Electrolyte & Water Homeostasis

• Block 4 covers sodium, water, potassium, calcium, electrolyte and water homeostasis, buffers, kidney pH homeostasis, hydrogen, respiration, red blood cells (hemoglobin), and lung respiration.

Sodium & Water Objectives

• Understand the regulation of plasma osmolality and the role of osmoreceptors in antidiuretic hormone (ADH) release.
• Understand the mechanism of action of ADH, as well as its physiological effects.
• Understand the renal mechanisms (transporters) involved in plasma $Na^+$ homeostasis, including the role of aldosterone.
• Know the mechanism of water and chloride reabsorption.
• Define the regulation and effect of atrial natriuretic peptide.

Kidney (Review)

• Kidneys regulate plasma (water) and plasma ions, i.e., what is filtered.
• The majority of reabsorption occurs in the proximal tubule (~60%), followed by the loop of Henle.
• Given the large amount of sodium that is filtered/reabsorbed, the reabsorption of sodium is critical for water reabsorption (osmosis) and other solutes (glucose, chloride).
• Reabsorption early in the nephron is obligate (not regulated); in the late distal tubule/collecting duct, hormones (aldosterone) regulate reabsorption.

Electrolytes

• In each compartment, the total number of anions = the total number of cations.
• Osmolality - the number of solute particles dissolved in solution (water) - is identical in all compartments. Osmolality reflects two variables – solute and water – that can be independently regulated.
• The input and output of electrolytes are matched.

Sodium & Volume

• Renal regulation of salt (sodium, $Na^+$) and water controls plasma volume. As sodium is largely extracellular, the kidney is filtering a ‘large’ sodium load.
• Volume homeostasis is dependent upon retention or excretion of water and sodium by kidneys.
• Loss/gain of $Na^+$ = loss/gain of water; regulation of $Na^+$ is linked to volume regulation.
• No receptors directly monitor fluid or electrolyte balance, i.e., blood pressure (baroreceptors; Block 3) or osmolality are sensed.
• Kidneys control osmolality by excreting either a concentrated (i.e., greater proportion of solutes) or dilute (i.e., greater proportion of water) urine; i.e., independently regulating solute and water excretion.

Regulation of Blood Osmolality

• Kidneys control osmolality (solute concentration) of body fluids by excreting either a concentrated (i.e., greater proportion of solutes) or dilute (i.e., greater proportion of water) urine.
• The major determinant of plasma osmolality is $Na^+$. Therefore $[Osm]<em>{plasma}$ is a function of $[Na^+]</em>{plasma}$, and when $[Na^+]<em>{plasma} \uparrow$, $[Osm]</em>{plasma} \uparrow$.
• Osmoreceptors in the hypothalamus detect increases in osmolality. This triggers:
  • Thirst
  • Decreased excretion of water in urine
• When plasma osmolality is low, osmoreceptors are not stimulated, so more water is excreted in urine.

Antidiuretic Hormone (ADH)

• The collecting duct is impermeable to $Na^+$ but permeable to water.
• In the collecting duct, permeability to water depends on the number of aquaporin (water) channels on the membrane, which is regulated by ADH (antidiuretic hormone).
• ADH is produced by neurons in the hypothalamus but stored and released from the posterior pituitary gland—release stimulated by an increase in plasma osmolality (sensed by osmoreceptors).
• ADH binds to receptors on collecting duct cells à vesicles with aquaporin channels fuse to plasma membrane.
• Aquaporins are removed from the membrane without ADH.

ADH Secretion

• Stimulus, receptors, and effects on ADH secretion and urine volume are listed.
  • Increased osmolality (dehydration) sensed by osmoreceptors in the hypothalamus leads to increased ADH secretion, increased water retention, and decreased blood osmolality. Water loss increases blood osmolality.
  • Decreased osmolality sensed by osmoreceptors in the hypothalamus leads to decreased ADH secretion and increased urine volume.
  • Decreased blood volume sensed by stretch receptors in the left atrium leads to increased ADH secretion.
  • Increased blood volume sensed by stretch receptors in the left atrium leads to decreased ADH secretion.

Antidiuretic Hormone

• Vasopressin causes insertion of water pores into the apical membrane.
• Water is absorbed by osmosis into the blood.
• Cell inserts AQP2 water pores into the apical membrane.
• Receptor activates cAMP second messenger system.
• Vasopressin binds to membrane receptor.

Control of Vasopressin Secretion

• Decreased blood pressure sensed by carotid and aortic baroreceptors leads to increased vasopressin secretion.
• Decreased atrial stretch due to low blood volume sensed by atrial stretch receptors leads to increased vasopressin secretion.
• Osmolarity greater than 280 mOsM sensed by hypothalamic osmoreceptors leads to increased vasopressin secretion.
• Vasopressin (AVP) is made and packaged in the cell body of the neuron in the hypothalamus, transported down the cell, stored in vesicles in the posterior pituitary, and released into the blood.
• Arginine Vasopressin (AVP), Antidiuretic hormone (ADH)
  • Origin: Hypothalamic neurons. Released from posterior pituitary
  • Chemical nature: 9-amino acid peptide
  • Transport in the circulation: Dissolved in plasma
  • Half-life: 15 min
  • Factors affecting release: Osmolarity (hypothalamic osmoreceptors), Blood pressure or volume (carotid, aortic, atrial receptors)
  • Target cells or tissues: Renal collecting duct
  • Receptor/second messenger: V2 receptor/cAMP
  • Tissue action: Increases renal water reabsorption
  • Action at cellular-molecular level: Inserts AQP water pores in apical membrane

Homeostasis of Plasma $Na^+$

• Low plasma $Na^+$ concentration/osmolality sensed by the hypothalamus. Negative feedback correction via increased $Na^+$ retention.
  • Increases in $Na^+$ intake.
  • Increases in $Na^+$ reabsorption in the cortical collecting duct.
  • Increases in aldosterone.
  • Increases in ADH, leading to water reabsorption in collecting ducts.
  • Increases in Angiotensin II, Renin, and sympathetic nerve activity.
  • Decreases urine volume.

$Na^+$ Reabsorption

• About 60% of filtered $Na^+$, $Cl^-$, and water is reabsorbed early in the nephron; not regulated, i.e., obligate reabsorption.
• $Na^+K^+ATPase$ (basolateral membrane) maintains a low intracellular concentration of $Na^+$, establishing a concentration gradient that allows for the reabsorption of sodium via a number of different transporters.
• The basolateral expression also ‘returns’ the reabsorbed $Na^+$ to the plasma.

$Na^+$ Reabsorption

• Proximal Tubule
  • $Na^+K^+ATPase$ on the basolateral membrane
  • Drives glucose reabsorption (SGLT; secondary active transport)
  • Drives amino acid reabsorption (variety of secondary active transporters)
  • Conserves bicarbonate (sodium hydrogen exchanger; NHE; secondary active transporters)
  • Important in regulating pH
• Ascending Limb
  • $Na^+K^+2Cl^-$
• Distal Tubule
  • $Na^+Cl^-$

Aldosterone

• Distal Tubular Mechanisms: Sodium reabsorbed independently of water; can alter sodium excretion when ingestion is not balanced by ingestion of water.
• Aldosterone: increases sodium reabsorption in distal tubules/collecting duct (principal cells) via ENaC (Epithelial Na Channel).
• Aldosterone is also regulated, in part, by AngII. Therefore, a decrease in blood pressure increases AngII, which increases sodium reabsorption, resulting in long-term correction to sodium content and blood pressure.
• Although aldosterone only regulates 2% of filtered sodium load, this amounts to 30 g NaCl/day

Regulation of Aldosterone Secretion

• A rise in blood $K^+$ directly stimulates production of aldosterone in the adrenal cortex.
• A fall in blood $Na^+$ indirectly stimulates production of aldosterone via the renin-angiotensin-aldosterone system.

Aldosterone-ENaC

• Aldosterone increases ENaC expression and $Na^+-K^+ ATPase$ expression.
• Reduced $Na^+$ influx decreases the electrogenic exchange of $Na^+$ for $K^+$ & H+, which can cause hyperkalemia & acidosis.
• 2-5% of filtered $Na^+$ is normally reabsorbed in the collecting duct.

Water

• Proximal Tubule
  • >60% reabsorbed in the proximal tubule
  • Aquaporins
  • Paracellular
• Descending Limb
  • Aquaporins
• Ascending Limb//Distal Tubule
  • Impermeable
• Collecting Duct
  • ADH regulation of Aquaporins

Chloride ($Cl^-$

• Proximal Tubule
  • >60% reabsorbed in the proximal tubule
  • Transporters
  • Paracellular (with water)
• Ascending Limb
  • $Na^+K^+2Cl^-$
• Distal Tubule
  • $Na^+Cl^-$

Atrial Natriuretic Peptide

• Increases in blood volume also increase the release of atrial natriuretic peptide hormone from the atria of the heart when atrial walls are stretched.
• Stimulates kidneys to excrete more salt (decreased aldosterone) and therefore more water
• Decreases blood volume and blood pressure

Summary

• Osmolality is sensed and regulated by renal reabsorption/excretion of solute (sodium) and water.
• ADH, secreted by the posterior pituitary, regulates aquaporin expression at the plasma membrane of collecting duct cells.
• $Na^+K^+ATPase$ is critical for the reabsorption of sodium; the sodium gradient allows for cotransport (reabsorption) of a number of solutes.
• Aldosterone, secreted by the adrenal gland, regulates ENaC expression and therefore sodium reabsorption at the plasma membrane principal cells in the collecting duct cells.
• Water and chloride reabsorption can be paracellular and transporter-mediated; aquaporin expression is regulated in collecting duct by ADH.
• Atrial natriuretic peptide (ANP) is released by the atria in response to increased plasma volume and increases sodium/water excretion.