Osmoregulation: Control and Abnormalities of Body Water

• What is osmoregulation?

  Osmoregulation is the process by which the body maintains fluid balance and the concentration of solutes (mainly sodium) in the extracellular fluid (ECF) to ensure homeostasis
• Why is fluid balance important in the body?

   Fluid balance ensures:

  • Proper cellular function (prevents dehydration or overhydration)
  • Stable blood pressure and circulation
  • Optimal kidney function
  • Electrolyte homeostasis
• What is the key hormone regulating body water levels?

  Antidiuretic hormone (ADH) / Vasopressin, secreted by the posterior pituitary, controls water reabsorption in the kidneys to regulate fluid balance.
• Where is ADH synthesised and released?

  • ADH is synthesised in the hypothalamus (specifically in the supraoptic and paraventricular nuclei).
  • It is stored and released from the posterior pituitary gland in response to changes in osmolality or blood volume.
• What are the main stimuli for ADH release?

  1. Increased plasma osmolality (detected by osmoreceptors in the hypothalamus)
  2. Decreased blood volume or pressure (sensed by baroreceptors in the heart and blood vessels)
  3. Angiotensin II (as part of the renin-angiotensin-aldosterone system, RAAS)
  4. Stress, nausea, pain, and some drugs (e.g., nicotine, morphine)
• What inhibits ADH secretion?

  • Decreased plasma osmolality (detected by osmoreceptors)
  • Increased blood volume/pressure (sensed by baroreceptors)
  • Alcohol and caffeine (they promote diuresis by reducing ADH secretion)
  • Atrial natriuretic peptide (ANP) (released when blood volume increases)
• How do osmoreceptors in the hypothalamus regulate ADH release?

  • Located in the hypothalamus, osmoreceptors detect changes in blood osmolality.
  • If plasma osmolality rises, water moves out of osmoreceptor cells, causing them to shrink → stimulates ADH release.
  • If plasma osmolality falls, water enters osmoreceptor cells, causing them to swell → inhibits ADH release.
• How do baroreceptors regulate ADH secretion?

  • Baroreceptors are pressure-sensitive receptors in the carotid sinus, aortic arch, and atria.
  • If blood pressure drops, they reduce their firing rate → signals the hypothalamus to release more ADH.
  • If blood pressure rises, they increase their firing rate → inhibits ADH release.
• What is the mechanism of ADH action in the kidneys?

  1. ADH binds to V2 receptors on the basolateral membrane of principal cells in the collecting ducts.
  2. This activates the cAMP-PKA pathway, leading to insertion of aquaporin-2 (AQP2) channels into the apical membrane.
  3. Water is reabsorbed from the filtrate into the blood, reducing urine output and increasing blood volume.
  4. When ADH is absent, AQP2 is removed, and water remains in the filtrate, leading to dilute urine.
• How does ADH influence urine concentration?

  • High ADH levels → Increased water reabsorption → Concentrated (hyperosmotic) urine
  • Low ADH levels → Reduced water reabsorption → Dilute (hypoosmotic) urine
• How does the body respond to dehydration?

  1. Plasma osmolality increases, detected by hypothalamic osmoreceptors.
  2. ADH release increases, promoting water reabsorption in the kidneys.
  3. Urine becomes concentrated, and thirst is stimulated to restore fluid balance.
• What happens in the body when there is excess water intake?

  1. Plasma osmolality decreases, causing osmoreceptors to swell.
  2. ADH secretion is suppressed, reducing water reabsorption.
  3. Dilute urine is produced to remove excess water.
• What is the relationship between plasma sodium concentration and extracellular fluid (ECF) osmolality?

  Plasma sodium concentration directly affects ECF osmolality. Sodium is the major cation in the extracellular space and helps maintain osmotic balance.
• What happens when plasma sodium concentration increases?

  Increased plasma sodium → increased ECF osmolality (hypertonic). This causes water to move from inside cells to the extracellular space.
• What happens when plasma sodium concentration decreases?

  Decreased plasma sodium → decreased ECF osmolality (hypotonic). This causes water to move into cells.
• Why is plasma sodium concentration important for ECF osmolality?

  Plasma sodium concentration is crucial because sodium is the most abundant ion in the extracellular fluid (ECF).
• How does sodium affect water movement between compartments?

  Water moves between intracellular and extracellular compartments based on osmotic gradients, which are largely determined by sodium concentration.
• What happens when plasma sodium concentration changes?

  When plasma sodium rises or falls, the osmotic balance is disrupted, causing water shifts that affect the volume and composition of body fluids.
• What is hypernatremia?

  Hypernatremia is when plasma sodium is greater than 145 mmol/L.
• What happens to extracellular fluid osmolality in hypernatremia?

  Hypernatremia increases extracellular fluid osmolality, making the ECF hypertonic.
• What is the effect of hypernatremia on cells?

  The osmotic gradient caused by hypernatremia pulls water from cells into the ECF, leading to cellular dehydration (shrinkage).
• How does the body try to compensate for hypernatremia?

  The kidneys conserve water, reducing urine output, and thirst is stimulated to increase water intake.
• What can happen if hypernatremia is not corrected?

  If untreated, hypernatremia can lead to severe dehydration, neurological symptoms, and organ dysfunction.
• What happens to extracellular fluid osmolality during hyponatremia (low plasma sodium)?

  Hyponatremia (plasma sodium < 135 mmol/L) causes decreased extracellular fluid osmolality, making it hypotonic.
• What happens to water movement during hyponatremia?

  Water moves from the extracellular fluid into cells, causing cellular swelling.
• What can severe hyponatremia lead to?

  Severe hyponatremia can cause brain oedema, leading to neurological issues like confusion, seizures, and coma.
• How does the body try to respond to hyponatremia?

  The kidneys try to excrete excess water, but if sodium remains low, the body struggles to restore balance.
• What system regulates plasma sodium and extracellular fluid osmolality?

  The renin-angiotensin-aldosterone system (RAAS) and antidiuretic hormone (ADH) are key regulators.
• What does ADH (Vasopressin) do?

  ADH increases water reabsorption in the kidneys when plasma osmolality is high, diluting the plasma and lowering osmolality.
• What does aldosterone do?

  Aldosterone promotes sodium retention in the kidneys when sodium is low or blood volume is low, increasing plasma sodium and osmolality.
• How do ADH and aldosterone work together?

  ADH and aldosterone help restore balance by regulating water and sodium in the body, maintaining plasma sodium and osmolality levels.
• How does the body respond to hypernatremia (increased plasma sodium)?

  • ADH secretion increases to promote water retention in the kidneys.
  • Thirst is stimulated to increase water intake.
  • The kidneys reduce sodium excretion to preserve water and restore balance.
• How does the body respond to hyponatremia (decreased plasma sodium)?

  • ADH secretion decreases, promoting water excretion in the kidneys.
  • Aldosterone release may increase to conserve sodium.
  • Thirst is suppressed to avoid further dilution of plasma sodium.
• What is hyponatraemia, and what are its main causes?

  • Hyponatraemia: Low sodium levels in the blood (<135 mmol/L).
  • Causes:

  1. SIADH (Syndrome of Inappropriate Antidiuretic Hormone): Excess ADH leads to water retention, diluting sodium levels.
  2. Heart failure: Decreased cardiac output triggers water retention.
  3. Liver disease: Cirrhosis can cause fluid retention and dilution of sodium.
  4. Kidney disease: Impaired renal excretion of water.
  5. Hypothyroidism: Low thyroid hormones can lead to fluid retention.
  6. Excessive water intake (water intoxication): Overconsumption dilutes sodium in the blood.
•  What is hypernatraemia, and what are its main causes?

  • Hypernatraemia: High sodium levels in the blood (>145 mmol/L).
  • Causes:

  1. Dehydration: Inadequate water intake or excessive water loss (e.g., diarrhea, vomiting).
  2. Diabetes Insipidus (DI): Lack of ADH or kidney resistance to ADH leads to excessive water loss.
  3. Excessive salt intake: Rare but possible in cases of overconsumption.
  4. Renal disease: Impaired kidney function leads to reduced ability to excrete sodium.
• What is SIADH, and how does it contribute to hyponatraemia?

  • SIADH (Syndrome of Inappropriate Antidiuretic Hormone):
  • Overproduction of ADH causes excessive water reabsorption in the kidneys, leading to dilution of sodium in the blood.
  • Common causes: tumors (e.g., small cell lung cancer), CNS disorders (e.g., stroke, infections), and medications (e.g., SSRIs).
  • Leads to water retention and hyponatraemia without significant edema due to the excess water being intracellular.
• What is Diabetes Insipidus (DI), and how does it contribute to hypernatraemia?

  • Diabetes Insipidus (DI):
  • A disorder characterized by insufficient ADH or the kidneys’ inability to respond to ADH, leading to excessive water loss through urine.
  • Types:

  1. Central DI: Due to a lack of ADH production (e.g., pituitary damage).
  2. Nephrogenic DI: Kidney resistance to ADH (e.g., due to genetic mutations or drugs like lithium).

  • Result: Increased urine output (polyuria) and water loss, which can lead to hypernatremia due to dehydration.
• How can SIADH and Diabetes Insipidus be differentiated based on sodium levels and urine output?

  • SIADH:
  • Sodium levels: Low (hyponatraemia).
  • Urine output: Low (concentrated urine despite low blood sodium).
  • Cause: Water retention due to excess ADH.
  • Diabetes Insipidus:
  • Sodium levels: High (hypernatraemia).
  • Urine output: High (dilute urine due to lack of ADH action).
  • Cause: Excessive water loss due to insufficient ADH or kidney resistance.