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Hyponatremia vs Hypernatremia

Hyponatremia = plasma Na+ <135 mmol/L (usually excess water); Hypernatremia = plasma Na+ >145 mmol/L (usually water deficit), changes plasma ADH levels

ADH (Vasopressin): Origin/Release

Produced in hypothalamic supraoptic/paraventricular nuclei (connected to OVLT and SFO axons) and released from posterior pituitary in response to ↑ plasma osmolarity or ↓ blood volume/BP

ADH functions

Increases H2O permeability in collecting ducts, increases urea permeability in inner medullar collecting ducts and constricts arterioles in peripheral smooth muscle (increasing blood pressure), produces concentrated, low-volume urine

ADH Receptors

V2 receptors increase water and urea reabsorption in collecting ducts; V1 receptors cause arteriolar vasoconstriction to raise BP

Osmoreceptors (definition)

OVLT and SFO detect plasma osmolarity via mechanosensitive cation channels exposed to blood through fenestrated capillaries

Osmoreceptor Response

Hyperosmolarity shrinks osmoreceptors → ↑ firing → ADH release; hypotonicity swells cells → ↓ firing → suppresses ADH

ADH vs Thirst Threshold

A 1–2% rise in osmolarity stimulates ADH release, 2–3% rise stimulates thirst

Normal Plasma Osmolarity

Normal plasma osmolarity is ~275–290 mOsm/kg; below threshold ADH secretion is essentially absent

Non-osmotic ADH Control

A 5–10% fall in blood volume/BP activates baroreceptors in the aorta and carotid sinus causing ADH release even during hypoosmolarity to preserve perfusion (blood pressure more important than osmolarity), resets osmostat

Other ADH Stimulators

Nausea pain motion sickness hypoxia strenuous exercise morphine nicotine MDMA and hypoglycemia increase ADH; alcohol suppresses it, thirst stimulated by decrease in blood volume

SFO Functions

SFO contains Ang II-sensitive neurons that stimulate thirst salt appetite and ADH release

Diabetes Insipidus (Central)

Central DI results from inadequate ADH production/release causing polyuria dilute urine and hypernatremia

Nephrogenic Diabetes Insipidus

Normal ADH but kidneys fail to respond causing polyuria dilute urine and hypernatremia

SIADH

SIADH causes excessive ADH leading to water retention hyponatremia low plasma osmolarity and concentrated urine

Sodium Balance: Main Determinant of ECF Volume

Total extracellular Na+ is the primary determinant of ECF volume because NaCl is the major extracellular osmotic solute

Kidney Regulation of Sodium Balance

The kidneys maintain ECF volume by matching Na+ excretion to dietary intake over a wide range

Primary Signals for Na+ Excretion

Vascular volume blood pressure and cardiac output regulate renal Na+ excretion through cardiovascular sensors

Response to Volume Changes

ECF contraction decreases Na+ excretion whereas ECF expansion increases Na+ excretion (natriuresis)

Congestive Heart Failure & Sodium

CHF causes edema with low effective arterial volume so kidneys retain Na+ and water despite increased total ECF volume

Major Baroreceptors

Atria pulmonary vessels carotid sinus aortic arch afferent arteriole and macula densa detect changes in vascular volume/pressure

Renal Sympathetic System

Sympathetic activation decreases GFR stimulates proximal Na+ reabsorption and renin release causing Na+ retention

RAAS Activation

Reduced renal perfusion sympathetic stimulation or decreased NaCl at macula densa stimulates renin release

RAAS Pathway

Renin converts angiotensinogen→Ang I; ACE converts Ang I→Ang II; Ang II stimulates aldosterone secretion

Major Actions of Angiotensin II

Causes vasoconstriction stimulates aldosterone ADH thirst salt appetite and increases proximal tubule Na+ reabsorption

Aldosterone Function

Aldosterone increases collecting duct Na+ reabsorption expanding ECF volume while promoting K+ secretion

ANP: Origin & Stimulus

Produced by atrial myocytes and released in response to atrial stretch during volume expansion

ANP Actions

ANP increases GFR inhibits renin aldosterone and ADH and increases Na+ and water excretion

Euvolemia

Euvolemia exists when renal Na+ excretion equals dietary intake with collecting duct Na+ reabsorption regulated mainly by aldosterone

Hypovolemia vs Hypervolemia

Hypovolemia activates sympathetic nerves RAAS and ADH to retain Na+/water; hypervolemia activates ANP and suppresses RAAS

Potassium Balance: Distribution

About 98% of body K+ is intracellular so small shifts between ICF and ECF greatly alter plasma K+

Normal Plasma Potassium

Normal plasma K+ ≈4 mEq/L; hypokalemia

Internal vs External K+ Balance

Internal balance shifts K+ between cells and ECF while external balance is regulated by renal excretion matching intake

Importance of Cellular Buffering

Rapid cellular uptake after meals prevents life-threatening hyperkalemia because renal excretion is relatively slow

Factors Moving K+ Into Cells

Insulin β2 agonists α antagonists alkalosis and aldosterone shift K+ into cells causing hypokalemia

Factors Moving K+ Out of Cells

Insulin deficiency β2 antagonists α agonists acidosis hyperosmolarity cell lysis and exercise shift K+ out causing hyperkalemia

Insulin & Potassium

Insulin stimulates Na+/K+-ATPase causing rapid K+ uptake into cells after meals; insulin deficiency predisposes to hyperkalemia

Adrenergic Effects on Potassium

β2 stimulation promotes K+ uptake whereas α stimulation promotes K+ release from cells

Acid-Base Effects on Potassium

Acidosis shifts K+ out of cells increasing plasma K+; alkalosis shifts K+ into cells decreasing plasma K+

Hyperosmolarity & Potassium

Hyperosmolarity pulls water from cells increasing intracellular K+ concentration and promoting K+ exit

Cell Lysis & Exercise

Cell lysis releases intracellular K+ while strenuous exercise transiently raises plasma K+

Aldosterone & Potassium

Aldosterone stimulates Na+/K+-ATPase promoting cellular K+ uptake; excess causes hypokalemia and deficiency causes hyperkalemia

Renal Handling of Potassium

K+ is freely filtered; ~65% reabsorbed in proximal tubule ~20% in thick ascending limb with variable secretion/reabsorption distally

Collecting Duct Potassium Secretion

Principal cells secrete K+ via apical K+ channels after uptake by basolateral Na+/K+-ATPase

Driving Force for K+ Secretion

High intracellular K+ plus a negative tubular lumen favor K+ secretion into tubular fluid

Aldosterone & Renal K+ Secretion

Aldosterone increases ENaC Na+/K+-ATPase and K+ channel expression enhancing K+ secretion largely by increasing Na+ reabsorption

Acid-Base Effects on Renal K+ Handling

Alkalosis increases renal K+ secretion whereas acidosis decreases secretion by altering Na+/K+-ATPase and K+ channel activity

High Potassium Diet

High K+ intake increases intracellular K+ in principal cells increasing the driving force for urinary K+ secretion

Low Potassium Diet

Low K+ intake decreases principal cell secretion and stimulates α-intercalated H+/K+-ATPase to reabsorb K+

α-Intercalated Cells

Reabsorb K+ through apical H+/K+-ATPase during K+ depletion helping conserve body potassium

Major Regulators of Renal K+ Secretion

High dietary K+ aldosterone and alkalosis increase secretion whereas low dietary K+ and acidosis decrease secretion