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Kidney Lect 9

Disorders of Tonicity: hyponatremia and hypernatremia

To excrete significant free water (i.e., urine with an osmolality as low as 50-75 mOsm/kg H 2 O), one needs: A. Delivery of solute and water to diluting sites. B. Proper function of the diluting segment. C. ADH must be absent for the collecting duct to be impermeable to water.
In what instances is delivery of solute and water to diluting sites compromised? Renal failure, volume depletion or effective circulating blood volume (ECBV) depeltion; in both of these, there is less distal delivery of solute and water, and proximal tubular Na and H2O reabsorption are increased
In what instances is proper function of the diluting segment compromised? Loop diuretics (block dilution of urine); osmotic diuretics (prevent reabsorption by thick ascending limb)
ADH is associated with conditions with ... hypotonicity (and hyponatremia).
To retain significant free water (i.e., maximally concentrate the urine to 1000 - 1200 mOsm/kg), one needs: A. Concentrated medullary interstitium due to solute reabsorption in the thick ascending limb of Henle B. ADH insertion of water channels into the apical membranes of collecting duct cells. C. Ability of collecting duct cells to respond to ADH
Hypertonicity (and hypernatremia) occurs if ... the patient is unable to concentrate their urine and if thirst or access to free water is compromised.
The normal [Na + ] in the serum is ____. 140 mEq/L.
Hyponatremia, a low serum sodium concentration, usually indicates that the ____ _____ is low. plasma osmolality
When hyponatremia is noted, the ____ ____ should be measured to determine whether the hyponatremia reflects ____ of the plasma. plasma osmolality; hypotonicity
Types of hyponatremia: (3) Hypertonic, isotonic, and hypotonic
Hypertonic hyponatremia hyperglycemia or mannitol therapy => osmotic shift of water from ICF to ECF, diluting ECF [Na + ] (e.g., [Na + ] tends to decrease ~1.6 mEq/L for every 100 mg/dL [glucose] is above its normal value of 100 mg/dL)
Isotonic hyponatremia lab artifact w/ marked elevation of plasma lipids or protein - no longer encountered in most clinical labs due to use of ion-specific electrodes
Hypotonic hyponatremia most common and important clinically; from this point on, we will consider only hypotonic hyponatremia, but you should always rule out the other types when evaluating a hyponatremic patient
How does hyponatreamia develop? Etiology Etiology: H 2 O intake > H 2 O excretion: may be due to huge intake of fluids (normal kidney can filter out 20 L /day; lower if kidney injured)
How does hyponatremia develop? Physiology The underlying physiology for the development of hypotonic hyponatremia is either: (1) huge water intake with normal water excretion, or (2) normal water intake with impaired renal water excretion.
The finding of hypotonicity in a patient with normal renal function ALMOST always implies that... the urine is not maximally dilute, i.e., ADH is being secreted.
How can ADH be secreted when the osmolality of the body fluids is low? the effective circulating blood volume (ECBV) is low (remember that both volume status and plasma tonicity affect ADH release); low ECBV-->low renal perfusion and enhanced tubular fluid reabsorption-->decreased distal fluid delivery
Clinical manifestations of hyponatremia: acute Acute (< 48 hrs): Symptoms at [Na + ] of ≤ 125 mEq/L. Seizures and coma at ≤ 115 mEq/L.
Clinical manifestations of hyponatremia: chronic often asymptomatic until [Na + ] drops to ≤ 115 mEq/L; adaptation through loss of intracellular solutes (osmolytes)
Symptoms of hyponatremia (early and late/severe) mainly CNS: a. Early: nausea, malaise, headache, muscle twitching, lethargy b. Late/Severe: obtundation, seizures, coma, respiratory arrest
One convenient method used to evaluate the cause of hypotonic hyponatremia in a particular patient is to first ... assess and classify the patient's extracellular fluid (ECF) volume status.
What clinical signs (not CNS) are seen in patients with low-volume hyponatremia? Orthostasis, low jugular venous pressure, dry mucous membranes, poor skin turgor, absent axillary sweat, etc.
What extrarenal etiologies could cause Low ECF volume and low effective circulating blood volume with enhanced water intake. (low volume hyponatremia) low ECFV and ECBV is caused by Na + loss through GI tract, skin, third spacing (e.g., vomiting, diarrhea, blood loss, profuse sweating)
What renal etiologies could cause Low ECF volume and low effective circulating blood volume with enhanced water intake. (low volume hyponatremia) low ECFV and ECBV is caused by Na + loss via the kidneys (e.g., diuretics, osmotic diuresis). Diuretics, particularly thiazide diuretics, may result in a reduction in the ECF volume, leading to an increase in ADH release and in thirst
What physiological changes contribute to low-volume hyponatremia? Low ECFV + ECBV depletion-->ADH release shift to left + stepper slope-->thirst mechanisms activated-->increased water intake (thirst and decreased water excretion (ADH release)
How does a low ECBV contribute to low volume hyponatremia? significantly enhances proximal tubular fluid reabsorption => very limited delivery of fluid to distal nephron, which greatly limits the amount of water that could be potentially excreted by the kidneys, even if there were no ADH present
What physiological factors contribute to high ADH release during low-volume hyponatremia? High ADH - secondary to both low BP (stimulates ADH release via baroreceptors in the carotid sinus) and low ECBV stimulating ADH via volume receptors (atria and aortic arch)
What clinical signs are seen in patients with high-volume hyponatremia? Clinical: Edema, jugular venous distention, relative hypotension ± pulmonary edema; history of CHF, liver failure, or heavy proteinuria
What common etiologies contribue to high-volume hyponatremia? Why? severe heart failure, cirrhosis, and nephrotic syndrome: effective circulating blood volume is also decreased--> enhanced ADH release and thirst
Why is ECBV decreased in patients with severe heart failure? poor pump function, so poor renal perfusion
Why is ECBV decreased in patients with cirrhosis? Hypotension and redistribution of blood volume to splanchnic circulation, so poor renal perfusion
Why is ECBV decreased in patients with nephrosis? Low intravascular oncotic pressure, Or, with severe acute or chronic renal failure, there is generally ECF volume expansion with an inability to excrete water due to inadequate urine production.
What physiological factors cause impaired water excretion in high-volume hyponatremia? i. Low ECBV => very limited delivery of fluid to distal nephron ii. High ADH - secondary to both low BP and low ECBV iii. Renal failure
What clinical signs are seen in patients with normal volume-hyponatremia? Clinical: Patient is clinically euvolemic; i.e., not orthostatic and not edematous. Elements of the patient's history, current medications, and/or laboratory findings are very helpful in establishing the diagnosis.
Explain how normal volume hyponatremia could be cuased by Psychogenic polydipsia large water intake (>15-20 L/day) with maximally dilute urine (<100 mOsm); usually easy to identify these patients
Explain how normal volume hyponatremia could be cuased by diuretics subclinical ECBV depletion with enhanced ADH release, decreased distal fluid delivery, and enhanced response to the effects of ADH
Explain how normal volume hyponatremia could be cuased by glucocorticoid deficiency ⇑ADH; hemodynamic instability and failure to completely suppress ADH secretion through the normal feedback mechanism
Explain how normal volume hyponatremia could be cuased by hypothyroidism poor effective circulating volume due to poor pump function leads to ⇑ADH and diminished GFR and distal delivery of solute and water; ?direct renal tubular effects?
Explain how normal volume hyponatremia could be cuased by inappropriate ADH secretion (SIADH) too much ADH due to ectopic secretion (e.g., lung Ca.) or enhanced secretion from pituitary. urine must not be maximally dilute in the presence of plasma hypotonicity (i.e., ADH is being secreted). patients are in sodium balance
What causes SIADH? i. Tumors - esp. lung (e.g., small cell) ii. Pulmonary Disease - infectious iii. CNS Disorders - cerebral tumors, infections, bleeds iv. Drugs - e.g., carbamazepine, cyclophosphamide, clofibrate, SSRIs, phenothiazines, narcotics, nicotine
What are the general therapeutic approaches for hyponatremia? volume depletion: give isotonic IV fluid; correct increased ADH secretion
How would you correct increased ADH secretion that is causing hyponatremia? Correct underlying disorder if possible, restrict fluid intake, increase solute intake (high salt, protein), give salt tablets or hypertonic saline, use drugs to block ADH effect (demeclocycline, loop diuretics, aquaretics)
demeclocycline inhibits cellular effects of ADH in the collecting duct
loop diuretics (how can they be used to treat patients with increased ADH?) interferes with countercurrent multiplication mechanism, diluting the hypertonic medullary interstitium and thereby reducing the gradient for water reabsorption in the distal nephron
V 2 receptor antagonists ("aquaretics") override the effects of ADH in the distal nephron, thereby promoting free water excretion in the urine (good if ECF volume expansion but ECBV depletion)
What is the treatment for SIADH? Water restriction alone if [Na+]>120 and symptoms modest; chronic therapy: increase solute load, low-dose loop diuretics, demeclocycline may be helpful (NORMAL SALINE BY ITSELF MAY BE HARMFUL-->if given, give with loop diuretics)
What cells are most affected by hyponatremia? How do they brain and CNS: can cause swelling-->rise in ICP-->neurologic signs-->risk of central herniation-->increased outflow of cerebrospinal fluid (acute adaptation). Adaptation: net loss of organic osmolytes replace net loss of inorganic ions
The treatment and rate of attempted correction for any cause of hyponatremia depends on... the presence or absence of serious neurological manifestations
To treat severe hyponatremia (plasma [Na + ] < 120) with associated serious CNS disturbance (e.g., seizures)... hypertonic saline (or loop diuretics plus saline) is used to rapidly treat the hyponatremia over several hours (e.g., raising plasma [Na + ] by 1-1.5 mEq/L per hour over 3-4 hours)
in all cases of chronic hyponatremia it is very important not to... raise the plasma [Na + ] by more than ~10-12 mEq/L over the first 24 hours or severe brain damage may ensue (irreversible and severe CNS complication of central pontine myelinolysis (CPM) may result)
osmotic demyelination syndrome is thought to occur when ... (pathophysiology) osmotic shrinkage of axons induces demyelination by severing axon connections with surrounding myelin sheaths; may also be direct injury resulting from rapid increases in cellular cation content
Symptoms of central pontine myelinolysis can be delayed by 2-6 days after the overly rapid Na + correction and include dysarthria, dysphagia, paraparesis, lethargy and coma
How do you treat central pontine myelinolysis? no proven therapy for CPM, prevention by avoiding overly rapid correction is crucial; If overly rapid correction occurs, one should immediately stop any further rise in P Na and consider re-lowering P Na (by giving dDAVP or free water)
Hyponatremia is a ____ problem, not a ____ problem water, Na+; => water intake > water excretion
Causes of the defect in renal water excretion a. Low effective circulating blood volume limits volume of dilute urine delivered to distal diluting sites b. Elevated ADH causes reabsorption of the dilute urine
Therapy for hyponatremia a. Limit water intake; other adjunctive therapy if needed b. Identify and try to correct renal water excretion defect c. Correct slowly unless there are serious symptoms
What defect in water handling leads to hypertonicity? rates of water excretion have exceeded rates of water intake
An increase in plasma osmolality (above threshold) will result in ___ secretion, and eventually stimulate thirst ADH
Thirst and ADH will result in an increase in ____ ingestion and decrease in ____ excretion water; renal water
Excess accumulation of plasma solutes cannot occur if ___ mechanism is intact, the patient has free access to ____, and can ingest sufficient quantities of ___ to match rates of ___ intake thirst; water; water; water
individuals who have a hypothalamic lesion causing a defect in the thirst mechanism are prone to develop ___. hypernatremia
What patients are especially at risk for developing hypernatremia? individuals with hypothalamic lesion (causing defect in the thirst mechanism); elderly or infants without sufficient access to water
What are the (2) consequences of ECF hypertonicity? Cellular dehydration and clinical neurological consequences
How does ECF hypertonicity lead to cellular dehydration? ECF hypertonicity causes water to shift from the ICF to the ECF until the ECF P osm = the ICF P osm
How do brain cells respond to cellular dehydration? Of particular concern, brain cells, in response to cellular dehydration, generate “idiogenic osmoles” or organic osmolytes-->raise intracellular effective osmolality and cause water to reshift intracellularly to re-establish normal brain cell volume
a consequence of rapid correction of hypertonicity with free water repletion before idiogenic osmoles disappear is... cerebral edema (!)
Normal-volume hypernatremia - hypertonicity associated with a loss of ... electrolyte-free water (loss of pure water).
What are the (3 clasfficiations of the types of hypernatremia? normal, high, or low volume
What are the possible underlying causes of renal loses leading to normal volume hypernatremia? --central diabetes insipidus --nephrogenic diabetes insipidus
What are the possible underlying causes of extarenal loses leading to normal volume hypernatremia? --fever --high ambient temperature w/ excessive sweating --hyperventilation
Hypernatremia will NOT occur unless ... there is also a deficit in water intake
What is the pathophysiology of patients with normal volume hypernatremia? Water deficits are shared by the various fluid compartments according to the proportion of TBW in each compartment. (1/12 from plasma volume, 1/3 from ECF and 2/3 from ICF)--> usually clinically euvolemic
What is the history upon clinical presentation of a patient with euvolemic hypernatremia? --Presence of condition(s) that predispose(s) to electrolyte-free fluid loss --Lack of access to water or an appropriate sense of thirst --CNS symptoms
What are the physical exam findings upon clinical presentation of a patient with euvolemic hypernatremia? --Euvolemia --Normal to low blood pressure --No edema
What are the laboratory exam findings upon clinical presentation of a patient with euvolemic hypernatremia? --Hypernatremia --Urine: 1) large volume and dilute (<240 mOsm) => central or nephrogenic DI 2) small volume and concentrated (>600 mOsm) => insensible losses
Treatment of normal-volume hypernatremia Replace water deficits with p.o. water or electrolyte-free i.v. fluids (D 5 W). To prevent the development of cerebral edema, it is important to replace only ~1/2 of the deficit in the first 24-48 hours if the hypernatremia is chronic.
How could a central defect lead to euvolumic hypernatremia? What are the possible etiologies? Impairment due to reduced ADH secretion; May be partial or complete and is usually acquired: idiopathic (?autoimmune), destruction of posterior pituitary by trauma, surgery, neoplasm, cyst, CNS sarcoidosis, infection, vascular collapse, and bleed
How could a nephrogenic defect lead to euvolumic hypernatremia? What are the possible etiologies? Basic theme: inability of the collecting duct to respond to ADH. Congenital (ADH receptors, defects in aquaporin); chronic lithium treatment, tubulointerstitial or obstructive disease, hypercalcemia, or chronic severe hypokalemia.
How can you distinguish between central and nephrogenic euvolumic hypernatremia? CDI is often more acute. Administration of exogenous ADH (either intranasally or subcutaneously) can serve as a diagnostic test. The disorder will correct with CDI, and urine volume will decrease and U osm increase dramatically.
What is the most effective treatment for chronic euvolumic hypernatremia? If possible, correcting the underlying cause is the most effective long-term strategy; central DI-->stable dose of long acting ADH analog (e.g. dDAVP); nephrogenic: thiazide diuretics (NSAIDs maybe); limit salt protein intake;
when should amiloride be given to patients with chronic euvolemic hypernatremia? lithium-induced nephrogenic DI who need to remain on chronic lithium therapy; thiazide diuretic benefits + limits further lithium-induced damage to the collecting duct cells by inhibiting cellular lithium uptake through Na+ channels.
High-volume hypernatremia hypertonicity associated with a gain of solutes that expands the ECF compartment and contracts the ICF compartment.
What are the common causes of high volume hypernatremia? Often iatrogenic i. NaHCO3 therapy (each ampule is 1786 mOsm/kg H2O) ii. Hypertonic saline (3% = 513 mEq/L NaCl or ~1026 mOsm/kg H2O) iii. Salt poisoning in infants (e.g., incorrectly mixed formula) iv. Sea water ingestion
What are the common clinical presentation of high volume hypernatremia (physical exam, history, labs)? i. History: administration or ingestion of a hypertonic sodium fluid, CNS symptoms ii. Physical exam: evidence for increased ECBV (e.g., HTN, edema) iii. Laboratory findings: hypernatremia, Uosm >300 mOsm, elevated urine Na+
What is the goal of treatment of people with high volume hypernatremia? Because the ECF hypertonic sodium-containing solution increases ECF volume (excess Na+ is restricted to ECF), initial treatment is designed to remove Na+ from the ECF compartment
How is high volume hypernatremia treated? i. diuretics (esp., loop diuretics) first => removes Na+ and water ii. free water to replace water lost in urine from diuretic iii. dialysis may be necessary if patient has concomitant severe renal failure
Low-volume hypernatremia hypertonicity associated with the loss of hypotonic fluids (i.e., fluids containing more water than Na+). This causes both ECF volume depletion and a free water deficit (hypertonicity)
What are the major causes of low volume hypernatremia? Renal loses of hypotonic fluid (osmotic diuresis, diuretic therapy); GI losses (diarrhea, vomiting, surgical drains/fistulas)
what is the cause of osmotic diuresis? An osmotic diuresis leads to loss of sodium (hypovolemia) and water (hypertonicity), and both Na+ (and accompanying anions) and glucose contribute to the increase in plasma osmolality.
What types of patients are likely to suffer from osmotic diuresis? may be seen in patients who have high urea (BUN) secondary to high-protein enteral or parental feedings, patients who have received mannitol, or in diabetics with severe hyperglycemia and glucosuria.
what is the clinical presentation of low volume hypernatremia (history and physical)? i. History: CNS symptoms in association with: large urinary or GI fluid losses ii. Physical exam: evidence for hypovolemia (hypotension, orthostasis, no edema)
what is the clinical presentation of low volume hypernatremia (just labs)? --hypernatremia --urine - GI: low volume, high Uosm - diuretics and glucosuria (DM): higher volume, Uosm ~300
What is the treatment for low volume hypernatremia? Restore fluid volume with saline/isotonic fluids; give free water after ECFV reexpands; correct free water deficit slowly to prevent cerebral edema
Hypernatremia is generally a ___ problem, with a deficit of ___ water; free water relative to solutes
Patients must have ____ for hypernatremia to be sustained. impaired thirst or access to free water
Therapy a. Normal-volume hypernatremia: correct with free water repletion over at least 3 days.
Therapy a. High-volume hypernatremia: use diuretics in combination with free water to correct hypernatremia slowly over at least a few days (if onset was chronic)
Therapy a. low-volume hypernatremia: give isotonic saline or other volume expanders to replete ECF volume deficit, then correct free water deficit slowly over at least 3 days.
Created by: karkis77



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