Term
| What are the 3 major requires for achieving significant free water in urine (osmolality <75 mOsm/kg H2O)? |
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Definition
Get blood to diluting segments, dilution must be working and ADH must be lacking.
1) Must deliver solute and water to diluting sites
- Renal failure, volume depletion and effective circulating blood volume (ECBV) depletion will cause increased proximal tubular reabsorption, decreasing distal delivery
2) Diluting segments must function properly
- Loop diuretics that inhibit Na,K,2Cl- pump in TAL will prevent reabsorption and dilution of urine.
3) ADH must be absent for collecting duct to be impermeable to water. |
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Term
| What are the 3 requirements for maximal concentration of urine? |
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Definition
Gotta retain "free water"
1) Develop concentrated medullary interstitium by solute reabsortion in TAL
2) Presence of ADH to stimulate aquaporin insertion in apical membrane of collecting duct (cAMP mediated)
3) Collecting duct cells must be sensitive to ADH-aquaporin insertion. |
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Term
| What might happen to urine if a patient is thirsty of their access to free water is compromised? |
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Definition
| The body wants to keep more free water, so ADH-mediated aquaporin insertion in the apical membranes of the collecting ducts increases water reabsorption and facilitates CONCENTRATION of urine. |
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Term
| How does Hyponatremia relate to Hypotonicity? |
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Definition
Sodium is major extracellular ion (140 mEq/L). When it is low in the plasma, it signifies either
1) Low osmolality (hypotonic hyponatremia)
2) Significant concentrations of other osmotically active solutes |
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Term
| Why might a patient have hypertonic natremia? |
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Definition
| Hyperglycemia or Mannitol therapy, where there is an osmotic shift of water from ICF to EF, diluting ECF. |
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Term
| How does Hypotonic Hypernatremia develop? |
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Definition
Water intake > Water excretion (NOT a salt issue)
Either
1) Huge water intake with normal water excretion
- ADH is likely being secreted because of low effective ECBV (low renal perfusion), despite low body fluid osmolality.
2) Normal water intake with impaired renal water excretion |
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Term
| How do symptoms of chronic and acute hypotonic hyponatremia manifest clinically? |
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Definition
1) Acute occurs when Na+<125 mEq/L in <48h
- Seizures and coma occur at <115 mEq/L
2) Chronic occurs when Na+ <115 mEq/L, since there is adaptation by loss of intracellular solutes (osmolytes)
- Early features are nausea, malaise headache, muscle twitching and lethargy
- Late features are obtundation, seizures, coma and respiratory distress. |
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Term
A patient presents with Orthostatsis, low JVP, dry mucous membranes, poor skin turgor and absent axillary sweat.
You take a plasma sample as measure Na at 120 mEq/L.
What is the physiology underlying this condition? |
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Definition
Low-VOlume Hyponatremia caused by Renal (Na+ loss through kidneys because of diuretics) or Extrarenal etiologies (Na loss in GI, skin, third spacing).
1) Low ECF and ECBV causes ADH release curve to shift to left and have steeper slope due to low ECBV stimulus (Water retention)
- Low ECBV also maximizes solute reabsorption (90%) at proximal tubule and limits water excretion
2) Thirst is activated (increased water intake)
Together, thirst and ADH cause positive water balance and hyponatremia |
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Term
A patient with a history of liver failure presents with Edema, JVD, relative hypotension and pulmonary edema.
Lab tests come back and the patient is hyponatremic.
How could this condition arise? |
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Definition
High-volume Hyponatremia: There is low ECBV despite overall increase in ECF, which causes
*Restrict fluid intake**
Water excretion is impaired because:
1) little urine delivery to distal neuron (maximal reabsorption in proximal tubules)
2) High ADH (due to low ECBV and low BP/carotid sinus)
3) Renal failure
- Could be caused by
1) CHF (poor pump function)
2) Cirrhosis (Hypotension and redistribution of blood to splanchnic circulation) or
3) Nephrosis (Low IV oncotic pressure) |
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Term
A patient is euvolemic with no evidence of orthostatic hypotension or edema. However, their blood work shows hyponatremia.
What could have happened (5 causes) |
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Definition
Restrict fluid intake and increase solute intake
1) Psychogenic polydipsia- large water intake with maximally dilute urine
2) Diuretic-induced- Thiazides cause subclinical ECBV depletion and enhanced ADH release
3) Glucocorticoid deficiency- Increased ADH because of lack of suppression
4) Hypothyroidism- Poor ECBV because of poor pump function (no B1 insertion and lack of contractility) leads to increased ADH and diminished GFR and distal solute delivery
5) Syndrome of Inappropriate ADH Secretion (SIADH)
- Ectopic secretion (lung Ca.) or Enhanced pituitary secretion
- Diagnosis of exclusion, where urine is maximally dilute in the presence of hypotonicity |
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Term
| How can you diagnose a case of SIADH? What causes it? |
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Definition
1) Give them a normal saline challenge and look for natiuresis (sodium in urine)
2)
- Tumors (especially lung)
- Pulmonary Disease (pneumonia, abscess, TB)
- CNS disorder (cerebral tumors, infections, bleeds)
- Drugs
**Restrict fluid intake and increase solute intake!** |
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Term
| What are the therapeutic approaches to treating high ADH? |
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Definition
1) Correct underlying disorder if possible
- Adrenal insufficiency (Steroids)
- Hypothyroidism (THX)
2) Restrict fluid intake (high ADH is seen in normal or high volume hyponatremia)
3) Increase solute intake for patients with euvolemic hyonatremia due to SIADH
4) Drugs
- Demeclocycline- inhibits ADH effects at collecting duct
- Loop diuretics- Interferes with countercurrent multiplications, diluting hypertonic medullary interstitium and reducing gradient in distal tubule for water reabsorption.
- V2 antagonist "Aquaretics" |
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Term
| What drug options are available to treat high ADH in hyponatremia? |
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Definition
1) Demeclocycline- Inhibits ADH effect on collecting duct
2) Loop diuretics (Furosemde)- Interferes with countercurrent multiplication by diluting medullary interstitium and reducing gradient was water reabsorption in distal nephron.
3) V2 antagonists called "aquaretics" are especially effecting in high ECF low ECBV conditions (high volume hyponatremiia) caused by cirrhosis and CHF. |
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Term
| How do you most effectively treat SIADH? |
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Definition
Remember, this is euvolemic hyponatremia.
1) If Na>120, use water restriction alone
2) For chronic therapy, add solute load, low-dose loop diuretics and demeclocycline
**Don't give saline alone without diuretic, because body may just excrete the salt and keep the water, thereby worsening the hyponatremia!** |
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Term
| How does the brain and CNS adopt to hyponatremia? |
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Definition
| Counters cellular swelling by releasing K+ and other anions to reduce intracellular osmotic pressure. |
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Term
| When is central pontine myelinolysis (CPM) a concern? |
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Definition
This is a major irreversible CNS complication of raising plasma salt concentration by more than 10-12 mEq/L in the first 24 of treatment for hyponatremia.
- Osmotic demyelination occurs causing dysphagia, paraparesis, lethargy and coma.
**You want to raise it slowly with hypertonic saline (or saline with loop diuretic)** |
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Term
What is the treatment for the following scenario:
Hyponatremia with orthostasis and skin turgor.
What could be the cause? |
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Definition
Orthostasis and skin turgor in the setting of hyponatremia indicate a LOW VOLUME type with ECF volume depletion.
This could be due to 1) renal losses (if UnA> 20 meq/L) or 2) extra-renal losses ( UNa <10 meq/L) , but is always handled with Isotonic saline. |
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Term
What is the treatment for the following scenario:
Hyponatremia with peripheral and facial edema.
What could be the cause? |
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Definition
Hyponatremia in the context of edema indicates HIGH VOLUME status with ECF volume excess.
May be do to Nephrotic syndromes (Cirrhosis/CHF with Una <10 me/L) or Acute and chronic renal failure (Una >20 meq/L).
Treat with Water and Salt restriction. |
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Term
What is the treatment for the following scenario:
Hyponatremia (Una >20 meq/L) with orthostasis and skin turgor. |
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Definition
Low volume hyponatremia due to RENAL LOSSES
from Diuretic excess, Osmotic diuresis or Mineralocort. deficiency.
Treat with Isotonic saline |
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Term
What is the treatment for the following scenario:
Hyponatremia (Una <10 meq/L) with orthostasis and skin turgor. |
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Definition
Low Volume Hyponatremia due to Extrarenal losses such as Emesis, Diarrhea and "3rd spacin" from burns/trauma.
Treat with Isotonic saline (same as for renal loss) |
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Term
What is the treatment for the following scenario:
Hyponatremia (Una >20 meq/L) without edema |
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Definition
Normal Volume Hyponatremia with slight ECF volume excess due to
- Glucocorticoid deficiency
-Hypothyroidism
-Pain
-Drugs
-Emotional stress
-SIADH.
Treat with Water restriction. |
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Term
What is the treatment for the following scenario:
Hyponatremia (Una >20 meq/L) with edema |
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Definition
Sodium level indicates High Volume hyponatremia due to acute and chronic renal failure (vs. Cirrhosis or CHF for Una <10).
Treat with Water and Salt restriction. |
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Term
What is the treatment for the following scenario:
Hyponatremia (Una <10 meq/L) with orthostasis and skin turgor. |
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Definition
High Volume hyponatremia due to Nephrotic syndrome (Cirrhosis or CHF).
Treat with Water restriction and Salt restriction. |
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Term
| How can Hypertonicity develop? |
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Definition
H2O in < H2O out
Excess plasma solutes CANNOT accumulate if
1) Thirst is intact (hypothalamic lesion?)
2) Patient has access (infants and elderly) to free water and can ingest it |
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Term
| Why might cerebral edema occur in the context of treating hypertonicity? |
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Definition
In hypertonicity, cells are dehydrated. Patients may appear fatigued, lethargic, irritable and confused. They may even have seizures or comas.
- Brain adapts by producing idiogenic osmoles to raise intracellular effective osmolality.
- If you give free water too quickly, you will actually cause cellular swelling and edema. |
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Term
| Why are patients with pure water loss generally euvolemic? |
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Definition
| They lose very little water from the plasma volume (1/12 of the water lost). |
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Term
True or False:
Hypernatremia can occur is water intake is normal, but water excretion is increased? |
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Definition
False!
There MUST be a deficit in water intake because of lack of thirst or access to water. |
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Term
A patient with a history of low water access and confusion/lethargy presents a fever, sweating and hyperventilation. They have a normal BP and no edema, but is hypernatremic.
They are passing very little urine, but it is quite concentrated (>600 Osm)
How do you treat? |
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Definition
Normal volume hypernatremia due to Extrarenal fluid loss.
Fever, sweating and hyperventilation with small amount of concentrated urine fits extrarenal/insensible fluid losses.
Replace water with p.o. water or electrolyte-free IV fluids (ONLY 1/2 in first 24-48 hours because of cerebral edema risk!) |
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Term
A patient with a history of low water access and confusion/lethargy and central diabetes insipidus presents with normal BP and no edema, but is hypernatremic.
They are passing a large amount of dilute urine.
What is going on/treatment? |
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Definition
Hypernatremia due to renal losses of electrolyte-free water
Could be
1) Central DI, where ADH secretion is decreased or 2) Nephrogenic DI, where collecting duct does not respond to ADH
**Give exogenous ADH to tell between the two (CDI will respond and NDI will not)**
1) Chronic treatment of CDI should correct underlying cause. Also administer long acting ADH analog like dDAVP that does not bind vascular receptors.
2) Chronic NDI treatment is treated with thiazide diuretics, which will cause increased reabsorption in the proximal tubules, secondary to mild volume depletion downstream.
- Also can try limiting solute intake, NSAIDs (distal water reabsorption) and amiloride (especially for lithium-induced because it prevents distal tubule uptake of lithium by Na channels) |
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Term
| What chronic treatment options are available for Nephrogenic Diabetes Insipidus? |
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Definition
These patients are insensitive to ADH in their collecting ducts and tend to give off a large amount of dilute urine. They are most commonly acquired by chronic lithium treatment or obstructive disease.
1) Thiazide diuretics mildly decrease volume and therefore increase proximal tubule reabsorption, preserving the hypertonic medullary interstitium to support remaining ADH effect.
2) Limit solute intake
3) NSADs enhance distal water reabsorption
4) Amiloride is especially good for Lithium-induced cases, because it prevents lithium uptake by ENaC channels in the distal tubule/collecting duct. |
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Term
A patient presents with HTN and edema and their urine and plasma sodium levels are elevated.
How do you treat? |
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Definition
This sounds like high-volume hypernatremia (very often iatrogenic)
Treat with
1. diuretics (loops) to remove salt and water
2. free water to replace water lost in urine from diuretic
3. dialysis for severe renal failure |
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Term
A patient with a recent history of vomiting and diarrhea presents in a confused and lethargic state and you find hypernatremia on PE.
How do you treat? |
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Definition
Hypernatremia in the context of high GI fluid losses and CNS symptoms suggests a loss of hypotonic fluids in Low-volume hypernatremia (Loss of ECF AND free water)
1) ECF restoration with isotonic saline
2) Give free water AFTER ECF is restored (Hypovolemia was MORE worrisome than hypertonicity) and give it SLOWLY |
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Term
How does treatment differ for each of the following?
1) Normal volume hypernatremia
2) High volume hypernatremia
3) Low volume hypernatremia |
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Definition
1) Correct with free water over 3 days
2) Use diuretics in combination with free water to correct hypernatremia slowly over a few days (if chronic onset)
3) Give isotonic saline first, then correct free water slowly over 3 days. |
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Term
Patient presents with Diarrhea, sweating and hypertonic urine.
Whats going on and how do you treat? |
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Definition
Extrarenal loss of free-water causing urine concentration in LOW VOLUME hypernatremia (Na < H20 loss)
Give saline first, then give free water over 3 days |
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Term
Patient presents with severe hyperglycemia secondary to diabetes presents with evidence of hypovolemia and hypernatremia.
Their urine is isotonic.
Whats going on and how do you treat? |
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Definition
Low-volume hypernatremia due to renal losses of free water. Increased glucose in urine makes it isotonic.
Treat with saline first, then free water slowly |
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Term
How can you tell between renal losses and extrarenal losses of electrolyte-free water in normal volume hypernatremia?
Treatment? |
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Definition
Renal losses from CDI or NDE present with hypotonic urine, with ADH is not working (either synthesis or sensitivity).
Extrarenal losses due to respiratory or dermal insensible losses will present with small amount of hypertonic urine.
Treat with water replacement |
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Term
True or False:
High volume Hypernatremia presents with hypertonic urine. How do you treat? |
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Definition
True.
Increased solute intake (usually iatrogenic) will overwhelm re-absorptive capacity and must be treated with diuretics + water replacement. |
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