Renal2 Flashcards
Physiology of water balance
The kidneys normally maintain serum osmolality in a narrow range: 280-295 mOsm/kg. Water moves freely across cell membranes, in contrast to electrolytes.
What determines serum osmolality?
Sosm = 2x Na (mEq/L) + BUN (mg/dL):2.8 + Glucose (mg/dL):18
Hypertonicity
Can be caused by Hypernatremia, Uremia, Diabetic Coma, and Unmeasured osmoles, e.g. alcohols, glycin. When serum tonicity becomes elevated, Water moves freely across cell membranes, “Water shift hyponatremia”, and Hypertonic hyponatremia most often due to uncontrolled diabetes
ADH physiology
ADH causes water reabsorption in the renal collecting ducts. ADH increases if serum osmolality increases, to bring back serum osmolality to normal. ADH increases exponentially if blood volume decreases, despite a decrease in serum osmolality, leading to hyponatremia
How can blood volume decrease?
Hemorrhage. Plasma volume and EC fluid losses: Gastrointestinal loss, Renal loss (excessive use of diuretics, osmotic diuresis, mineralocorticoid deficiency), Excessive sweating, and Loss of sodium and water. This is hypovolemic hyponatremia
Signs of decreased blood volume
Low blood pressure and tachycardia. Orthostatic hypotension. Thirst, weakness, lethargy. Dry skin and mucous membranes. Low urine output, concentrated urine, low urine Na concentration (
Hypovolemic hyponatremia
Hypovolemia means decreased total body sodium. Total body water is also decreased, but to a lesser extent, because of appropriate ADH release. Treatment: Restore plasma volume by giving normal saline, ADH will fall, and normonatremia will follow
How else can “perceived” blood volume decrease?
There may be a decrease in “effective” blood volume, meaning decreased organ perfusion, due to a weak heart (congestive heart failure), or due to excessive vasodilatation such as in liver cirrhosis. The kidney increases tubular sodium and water reabsorption, leading to total body sodium and water excess, clinically manifest by edema.
ADH pathophysiology
In severe heart failure and liver cirrhosis “effective” blood volume is so low that ADH is stimulated and released, leading to more water reabsorption in the collecting duct, and hyponatremia develops. In these examples there is excess total body sodium (edema) and even more excess total body water. This is hypervolemic hyponatremia
Hypervolemic hyponatremia
Another mechanism (apart from ADH release) is intrinsic kidney disease. Either the diluting mechanism in the distal tubules does not work, or renal blood flow and glomerular filtration rate are too low, such as in advanced chronic kidney disease. Thiazide diuretics impair dilution and are a frequent cause of hyponatremia, particularly in the elderly (can be hypo-, hyper- or euvolemic)
Normal diluting system
- Normal function of ascending limb of Henle’s loop and of distal convoluted tubule. 2. Normal delivery of tubular fluid to the distal diluting segment of the nephron. 3. Normal suppression of ADH (vasopressin). Note: Free water excretion capacity is about 20% of GFR. Maximal urinary dilution: ~ 50 mOsm/kg
How to recognize and treat hypervolemic hyponatremia?
Edema, ascites, pleural effusions. History of heart, kidney or liver disease. Weight gain in short period of time. Treatment: Water restriction and loop diuretics, and treatment of the underlying condition. Note: Giving salt is a frequent mistake and makes the edema (and heart failure) worse!
Euvolemic hyponatremia
Hyponatremia is usually due to ADH secretion. Many stimuli can cause excessive ADH release: Hypothyroidism and adrenal insufficiency, nausea, pain, psychosis, and many medications, some of them commonly used (SSRI’s and antipsychotics, NSAIDS, and others). Syndrome of inappropriate ADH secretion (SIADH)
SIADH
Euvolemic hyponatremia and urine that is not maximally dilute (>50-100 mOsm/kg). Diagnosis of exclusion. Due to carcinomas (ectopic ADH production), CNS disorders, or pulmonary diseases
Symptoms of hyponatremia
Depend on rapidity with which hyponatremia develops (acute or chronic) and on severity. Anorexia, nausea, vomiting. Weakness, lethargy, confusion. Seizures, death. Symptoms likely due to cerebral edema
Treatment of euvolemic hyponatremia
If seizures, give hypertonic saline. If asymptomatic, water restriction and correction of underlying disorder or removal of offending drugs. If hyponatremia is chronic (> 48 hours) or unknown duration, slow correction to avoid central pontine myelinolysis (osmotic demyelination syndrome). ADH (vasopressin) antagonists
Hypernatremia
As with hyponatremia, total body sodium (volume) can be decreased, normal, or increased. Disorder of water balance, not primarily sodium. An increase in serum osmolality causes severe thirst. Therefore hypernatremia will only develop if the patient does not have access to water (often hospitalized patients) or has CNS pathology impairing thirst
What causes hypernatremia?
- Renal or extrarenal water losses that exceed sodium loss (hypovolemic hypernatremia). 2. Addition of hypertonic fluids (hypervolemic hypernatremia), usually iatrogenic (hypertonic saline, TPN or bicarbonate infusion). 3. Lack of ADH effect: Diabetes insipidus (water diuresis, very dilute urine)
Diabetes insipidus
2 possible causes: No ADH is secreted (ADH deficiency), or the kidneys do not respond to ADH (ADH resistance). Clinical manifestation is polyuria and polydipsia. Hypernatremia develops only if the patient cannot drink water (often in the hospital)
Central DI
ADH deficiency. Diseases of hypothalamus or pituitary gland (head trauma, surgery, tumors, encephalitis). 30-50% of cases are idiopathic (autoimmune?). Complete or partial DI. Kidneys respond to exogenous ADH (=AVP). Treatment with a long-acting, nasally administered analogue (DDAVP)
Nephrogenic DI
ADH resistance. The renal collecting duct does not respond to ADH. Therefore exogenous ADH will not raise Uosm. Congenital nephrogenic DI: due to mutation in AVP-receptor (V2R) gene (X-linked recessive; 90%) or due to mutation in aquaporin 2 gene (autosomal recessive or dominant; 10%). Symptoms in infants are failure to thrive and polyuria, fever, vomiting, seizures, death
Acquired nephrogenic DI
Much more common than congenital disease and usually less severe, and at least partially reversible. Causes are hypercalcemia, chronic hypokalemia. Long-term therapy with lithium. Other drugs (cidofovir, foscarnet, amphotericin B, ifosfamide). Chronic kidney disease. Chronic kidney disease causes a concentrating defect due to tubular dysfunction (medulla not maximally hypertonic) as well as ADH resistance/ Sickle cell anemia and polycystic kidney disease cause early concentrating defects by disrupting the medulla. Urinary obstruction causes ADH resistance
Pregnancy (gestational DI)
release of vasopressinase from the placenta during second half of pregnancy. If treatment necessary, DDAVP is resistant to vasopressinase
Symptoms of hypernatremia
Extreme thirst. Neuromuscular irritability with twitches, hyperreflexia, seizures. Altered mental status, confusion, coma. Failure to thrive in infants. High mortality rate in adults and children. Often a marker of serious underlying disease