osmoregulation - control and abnormalities of body water Flashcards
how is the osmolarity of the ECF adjusted ?
- There are just two ways to change the concentration of a solution
- Add/remove solute
- Add/ remove water
- The osmolarity of the ECF is adjusted by adding or removing water, not solute
How does the kidney regulate solute-free water excretion?
- Water excess: Large volume of dilute urine
- Water deficit: Small volume of concentrated urine
- The kidney must excrete ~600 mOsmol of solute daily, always in solution
- Urine concentration can vary to regulate water balance
- The kidney can effectively add or remove pure water to maintain ECF osmolarity
- Only the kidney can regulate water loss in this way
What are the two key mechanisms that allow the kidney to regulate urine concentration?
- Generation of hypertonic interstitial fluid in the medulla
Loop of Henle:
* Descending limb: Water reabsorbed, no solute
* Ascending limb: Solute reabsorbed, no water (via NK2C & NaCl cotransporters)
* Countercurrent system (vasa recta): Maintains a steep osmolarity gradient (300 mOsmol in cortex → 1200 mOsmol in deep medulla) - Generation of hypotonic tubular fluid
* Active transport of salts in the ascending limb → Dilute fluid enters collecting duct (CD)
How does the collecting duct regulate urine concentration and water excretion?
Urine concentration depends on CD water permeability:
* Impermeable CD → Large volume of dilute urine
* Permeable CD (due to osmotic gradient) → Small volume of concentrated urine
Limits of kidney function:
* Minimum urine osmolarity = very dilute
* Maximum urine osmolarity = matches medullary interstitial osmolarity
What happens to urine concentration in the absence of ADH?
- Urine entering the collecting duct (CD) is maximally dilute
- Osmotic gradient for water reabsorption is large, but CD is impermeable to water without ADH
- Maximally dilute urine (~50 mOsm/kg) is excreted
- Despite the osmotic gradient, water remains in CD → large volume of dilute urine
How does ADH control water reabsorption in the collecting duct?
- ADH increases CD water permeability
- Higher ADH → More water reabsorption → More concentrated urine
- Lower ADH → Less water reabsorption → More dilute urine
- Urine osmolality >100 mOsm/kg indicates presence of ADH (even at low levels)
Why is ADH essential for urine concentration?
- Without ADH, urine remains maximally dilute (~50 mOsm/kg)
- Concentrated urine (>500 mOsm/kg) requires significant ADH levels
- Normal urine is hypertonic (~500+ mOsm/kg) compared to plasma (~300 mOsm/kg)
What happens at maximal ADH levels?
- CD water permeability is maximized → Maximum water reabsorption
- Urine concentration reaches the osmolarity of the medullary interstitial fluid (~1200 mOsm/kg)
- Urine volume is minimized → Minimal water excretion
- Limit of concentration is set by the medullary interstitial osmolarity
what is the mechanism of ADH action ?
How does the body regulate ADH release to maintain osmolality?
- Osmoreceptors in the anterior hypothalamus detect changes in ECF osmolality
- Threshold for ADH release: 280-285 mOsm/kg
- ADH release is triggered by:
- Small changes in osmolality above 280-285 mOsm/kg
- Large decreases (10-15%) in blood volume/pressure
- ADH is released from the posterior pituitary by magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus
How is thirst regulated to maintain osmolality?
- Osmoreceptors in the anterior hypothalamus detect increases in ECF osmolality
- Threshold for thirst activation: Plasma osmolality ≥ 295 mOsm/kg
- Thirst centers are stimulated to induce a strong desire to drink
- Oropharyngeal and upper gastrointestinal receptors reduce thirst upon drinking
- Thirst is also stimulated by:
- Large drops (10-15%) in blood volume/pressure
- Angiotensin 2 acting on the hypothalamus
What is the relationship between plasma [Na+] and ECF osmolality?
- Plasma [Na+] (135-145 mmol/L) is the main determinant of ECF osmolality
- Principle of electroneutrality: Equal number of anions must balance Na+
- Mainly Cl-, HCO3-, and other anions
- Contribution of Na+ to osmolality: 2 x plasma [Na+]
- E.g., 140 mmol/L Na+ + 140 mmol/L A- = 280 mOsm/L
- Plasma osmolarity (mOsm/L) estimate:
2[Na+] + 2[K+] + [glucose] + [urea]
what is hypernatremia ?
- Water deficit
- ECF osmolality increases (hyperosmolality)
- (Na > 145)
what are the causes of hypernatremia ?
Gain of sodium (rare)
* Iatrogenic (via medication)
* Excess ingestion (rare)
* Excess mineralocorticoid activity
- e.g., primary hyperaldosteronism (Conn’s)
* Hypernatremia, if present, is usually mild
Loss of water (common)
* Can occur in various conditions associated with fluid loss (but loss of water must be relatively greater than loss of Na)
Extra-renal losses
* Dehydration
* Infection (increased losses via skin and lungs)
Renal losses
* Osmotic diuresis - increase urination
* Diabetes insipidus
what is diabetes insipidus ?
- Renal water loss (inability to concentrate the urine)
- Lack of effective ADH, either
- Central (failure of secretion)
- Nephrogenic (lack of renal response)
- Presents with polydipsia( xs urination) and polyuria (xs thirst)
- Thirst mechanism alone is normally enough to prevent significant hypernatremia
- But hypernatremia will rapidly develop if access to water is restricted
what is hyponatremia ?
- Water excess
- ECF osmolality decreases (hypoosmolality)
- (Na < 135)
what is hypoosmotic hyponatremia ?
- Sometimes considered ‘true’ hyponatremia
- ‘Pseudo’ hypontremia occurs when some other solute is present in sufficient quantity that the proportional contribution of sodium to plasma osmolality is reduced
- True hyponatremia is associated with hypoosmolality: it signifies water excess
What causes hyponatremia related to ADH?
- Continued water ingestion without reducing ADH secretion leads to hyponatremia
- Syndrome of Inappropriate ADH Secretion (SIADH):
Hyponatremia
High urine osmolarity - Causes of SIADH include:
CNS damage/disease
Ectopic ADH production by tumors - Under normal conditions the function of ADH is osmoregulation
- However, a large drop in arterial pressure is also a powerful stimulus for release
- In the hypovolemic state maximal renal water retention will dilute the ECF
- Low volume/pressure signal over-rules osmotic signals
