Water regulation Water Regulation Renal Na+ and water regulation work in tandem to control how fluid is distributed throughout the compartments of the body. Sodium is the body's dominant extracellular solute, and is responsible for the osmotic force that keeps differing amounts of water in each compartment. Changes in Na+ balance are sensed by the body through changes in blood volume. Renal Sodium and Water Regulation is controlled by the interplay between the osmoreceptors in the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus and the response to antidiuretic hormone (ADH) in the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys, resulting in very tight control of serum sodium and plasma osmolality.
- Detect changes in water balance as a result of changes in plasma osmolality:
- ↑ Water intake causes ↓ plasma osmolality (↓ serum sodium) → ↓ ADH release and ↓ thirst
- ↓ Water intake causes ↑ plasma osmolality (↑ serum sodium) → ↑ ADH release and ↑ thirst
- Maintain the plasma osmolality very tightly:
- ADH levels are minimal when plasma osmolality is normal (280–290 mmol/L).
- ADH increases linearly in response to very small changes in plasma osmolality.
Response to ADH in the kidney
- Aquaporin channels are the target of ADH:
- Allows water to move from the tubular fluid into the renal medulla via diffusion
- The renal medulla is hypertonic (due to the thick ascending limb and distal convoluted tubule).
- ADH stimulates the production and insertion of aquaporin channels in the collecting duct:
- High ADH levels → maximal levels of water reabsorption → concentrated urine
- Low ADH levels → minimal levels of water reabsorption → dilute urine
Etiologies of hypernatremia are organized according to volume status.
- Gain of more sodium than water
- Excessive intake of sodium:
- Infusion of isotonic saline, hypertonic saline, or sodium bicarbonate solutions
- Oral ingestion of salt tablets (i.e., for the treatment of hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia)
- Salt poisoning (i.e., excessive oral ingestion of table salt)
- Aldosterone mediated:
- Primary hyperaldosteronism Hyperaldosteronism Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis. Hyperaldosteronism
- Cushing’s syndrome
- Loss of water only
- Diabetes insipidus Diabetes Insipidus Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus (DI) (both central and nephrogenic)
- Lack of access to water:
- Altered mental status
- Mechanically ventilated patients
- Restrained patients
- Impaired thirst mechanism (elderly)
- Loss of more water than sodium
- GI losses:
- Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
- Nasogastric tube drainage
- Osmotic diuresis:
- Elevated urea from excessive tube feeding
- Recovery from AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
- Increased insensible water loss (i.e., sweat or burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns)
The primary clinical finding in hypernatremia is thirst. If the patient is unable to ingest enough water to keep their serum sodium from rising significantly, dehydration and neurologic findings may also occur. The severity of neurologic findings depends on the acuity and magnitude of the hypernatremia.
- Onset < 48 hours
- More likely to be symptomatic (due to less time for brain adaptation)
- Less severe increases in serum sodium are needed to induce symptoms.
- Onset > 48 hours
- Less likely to be symptomatic (due to adequate time for brain adaptation)
- More severe increases in serum sodium are needed before symptoms will appear.
- Neuromuscular irritability
- Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
- Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
In most cases, the etiology of hypernatremia will be clear and treatment can be initiated without any further testing. If the diagnosis is not clear, the following steps may be helpful:
- Quickly identify acute causes and very severe cases.
- Examples of acute causes: salt poisoning, DI patients without free access to water
- Example of a very severe case: Na > 160 mmol/L
- If acute, urgent and aggressive treatment is warranted.
- If severe but not necessarily acute, prioritize urgent treatment over definitive diagnosis.
- Identify reversible factors.
- Access to water/altered mental status (most likely lower the IV replacement rate once restored)
- Ongoing losses: Address any other factors to limit further free water replacement needs.
- Etiology unknown and only mild hypernatremia?
- Consider aldosterone-mediated causes.
- Cushing’s syndrome diagnosis: Check late-night salivary cortisol, 24-hour urine-free cortisol, and/or an overnight dexamethasone suppression test.
- Primary hyperaldosteronism Hyperaldosteronism Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis. Hyperaldosteronism diagnosis: Check plasma renin and aldosterone.
- Etiology unknown and not aldosterone-mediated?
- Measure urine osmolality.
- Urine osmolality < 300 mOsm/kg (< plasma osmolality): DI
- Give desmopressin (same as ADH).
- Urine osmolality increases: central DI
- No change in urine osmolality: nephrogenic DI
- Urine osmolality indeterminate (300–600 mOsm/kg): DI vs. osmotic diuresis
- Check the response to desmopressin to diagnose possible DI.
- Check total solute load to assess for osmotic diuresis.
- Urine osmolality > 600 mOsm/kg (usually nonrenal water loss (i.e., diarrhea)):
- Note: high urine osmolality represents the appropriate response by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys to high plasma osmolality in hypernatremia
Hypernatremia is treated by replacing the free water deficit by giving a hypotonic solution (i.e., 5% dextrose in water IV). Management is generally empirical with frequent monitoring of the serum sodium and adjustment of the fluid rate.
Volume status considerations:
- If hypotensive (hypovolemic):
- Give isotonic fluids to improve blood pressure.
- After blood pressure rises, switch to hypotonic fluids to address hypernatremia.
- If DI (euvolemic):
- Give hypotonic fluids to correct hypernatremia.
- Resume or start desmopressin to maintain normal serum sodium.
- If aldosterone mediated (hypervolemic):
- May only need free access to oral hypotonic fluids (hypernatremia should be mild)
- Treat the underlying condition.
Management according to acuity
- Uncommon (only occurs in specific situations):
- Salt poisoning
- DI without appropriate compensatory water intake
- Severe hyperglycemia without appropriate compensatory water intake
- Identify quickly due to the need for prompt and aggressive management.
- Goal: Replace 100% of the free water deficit within the 1st 24 hours.
- 5% dextrose in water IV to start
- Monitor serum sodium closely and adjust the fluid rate as needed:
- Initially monitor serum sodium and decrease fluid rate once serum sodium < 145 mmol/L.
- The goal is a decrease in serum sodium by 1–2 mEq/L/hour and a complete correction within 24 hours.
- Vast majority of hypernatremia
- Goal: Decrease serum sodium by 10 mEq/L/day (roughly 0.5 mEq/L/hour) until normal.
- 5% dextrose in water IV to start
- Oral free water is an option if hypernatremia is not severe.
- Monitor serum sodium and adjust the rate as needed.
- Overcorrection rarely causes clinical problems in adults but does in infants and children.
An acute rise in tonicity results in abrupt movement of fluid out of the brain. A slow rise in tonicity allows the brain to adapt and minimize the effect of fluid shifts. An overly rapid correction of hypernatremia could result in abrupt movement of fluid into the brain and cause cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema.
- Sudden rise in plasma tonicity → rapid shift of water out of the brain
- The brain essentially shrinks in volume.
- If severe enough, the shrinking can tear the brain’s blood vessels → intracranial hemorrhage and death
- Slower rise in plasma tonicity → slower shift of water out of the brain
- The brain responds with adaptive mechanisms to counter the water shift:
- Takes about 48 hours: the distinction between acute (< 48 hours) and chronic (> 48 hours) hypernatremia
- Net effect is a much smaller loss of brain volume → no tearing of vessels
- Does not, however, stop other symptoms from occurring (i.e., lethargy, confusion)
Overcorrection of acute hypernatremia
- Does not commonly cause clinical problems in adults
- Does commonly cause clinical problems in children and young adults (i.e., < 40 years old) with severe hyperglycemia (i.e., diabetic ketoacidosis Diabetic ketoacidosis Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises)
- Severe hyperglycemia results in glucose contributing a significant amount to hypertonicity.
- Plasma osmolality and serum glucose must be monitored very closely during treatment to prevent cerebral
Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity).
- Goal: decrease in plasma osmolality by < 3 mmol/kg/hour
- Goal: decrease in blood glucose by 50–75 mg/dL/hour
Overcorrection of chronic hypernatremia
- Water will always shift back into the brain as hypernatremia improves.
- If the water shift occurs too abruptly, cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and/or osmotic demyelination syndrome can occur.
- In practice, complications from hypernatremia overcorrection in adults are extremely rare:
- Goal for adults: Decrease serum sodium by approximately 10 mEq/L/day.
- Because overcorrection is not detrimental, therapeutic reraising of serum sodium is not recommended if the target is exceeded.
- Overcorrection is a common clinical problem with children and young adults:
- Smaller skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull volume → less margin for error if the brain shrinks or swells
- Much closer monitoring of treatment is needed.
- Goal for children and young adults: Decrease serum sodium by < 0.5 mEq/L/hour and < 10–12 mEq/L/day.
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