Sodium and Water Flashcards
Certain solutes, particularly ____, do not contribute to water shifts across most membranes and are thus known as ineffective osmoles.
urea
____ is the most abundant constituent in the body, comprising ~50% of body weight in women and 60% in men.
Water
The solute or particle concentration of a fluid is known as its _____, expressed as milliosmoles per kilogram of water (mOsm/kg).
osmolality
The major ECF particles are _____
Na +and its accompanying anions Cl – and HCO3–,
Predominant ICF osmoles.
K +and organic phosphate esters (ATP, c tine phosphate, and phospholipids)
Vasopressin secretion, water ingestion, and renal water transport collaborate to maintain human body fluid osmolality between ____ mOsm/kg.
280 and 295
AVP secretion is stimulated as _____ increases above a threshold level of ~285 mOsm/kg
systemic osmolality
there is a linear relationship between osmolality and circulating AVP
AVP has a half-life in the circulation of only ______;
10–20 min
AVP acts on renal, V 2 -type receptors in the ______ and principal cells of the _____, increasing intracellular levels of cyclic AMP and activating protein kinase A (PKA)–dependent phosphorylation of multiple transport proteins.
thick ascending limb of Henle
collecting duct (CD)
The AVP- and PKA-dependent activation of ______transport by the thick ascending limb of the loop of Henle (TALH) is a key participant in the countercurrent mechanism
Na+-Cl –and K+
AVP-induced, PKA-dependent phosphorylation of the aquaporin-2 water channel in ______ stimulates the insertion of active water channels into the lumen of the CD, resulting in transepithelial water absorption down the medullary osmotic gradient
principal cells
Arterial perfusion and circulatory integrity are, in turn, determined by ______, in addition to the modulation of systemic arterial resistance.
renal Na + retention or excretion
Approximately two-thirds of filtered Na+ -Cl – is reabsorbed by the _______, via both paracellular and transcellular mechanisms.
renal proximal tubule
The ____ subsequently reabsorbs another 25–30% of filtered Na+ -Cl – via the apical, furosemide-sensitive Na+ -K+ -2Cl – cotransporter.
TALH
The thiazidesensitive apical Na+ -Cl – cotransporter (NCC) reabsorbs 5–10% of filtered Na+-Cl –in the ____.
DCT
Reabsorb Na⁺ via amiloride-sensitive epithelial Na⁺ channels (ENaC).
Principal Cells
Approximately ____ of fluid enter the gastrointestinal tract daily, 2 L by ingestion and 7 L by secretion
9 L
Evaporation of water from the skin and respiratory tract (so-called _____) constitutes the major route for loss of solute-free water, which is typically 500–650 mL/d in healthy adults.
“insensible losses”
Reabsorb Cl⁻ via SLC26A4 anion exchanger (Cl⁻-OH⁻ and Cl⁻-HCO₃⁻ exchange).
Intercalated Cells
More reliable signs of hypovolemia include a decreased jugular venous pressure (JVP), orthostatic tachycardia (an increase of _____ beats/min upon standing), and orthostatic hypotension (a ______mmHg drop in blood pressure on standing).
> 15–20
> 10–20
______ is the most appropriate resuscitation fluid for normonatremic or hyponatremic patients with severe hypovolemia;
Isotonic, “normal” saline (0.9% NaCl, 154 mM Na+)
Hypernatremic patients should receive a ______, if there has only been water loss (as in DI), or ____ if there has been water and Na+-Cl –loss;
hypotonic solution 5% dextrose
hypotonic saline (1/2 or 1/4 normal saline)
Patients with bicarbonate loss and metabolic acidosis, as occur frequently in diarrhea, should receive ______
intravenous bicarbonate, either an
isotonic solution (150 meq of Na+ -HCO 3 – in 5% dextrose)
or a more hypotonic bicarbonate solution in dextrose or dilute saline.
_____ and _____constitute the two key effectors in the defense of serum osmolality
Water intake
circulating AVP
In contrast, abnormalities in sodium homeostasis per se lead to a deficit or surplus of whole-body Na+ -Cl – content, a key determinant of the _____ and circulatory integrity.
ECFV
Volume status also modulates the release of AVP by the _____, such that hypovolemia is associated with higher circulating levels of the hormone at each level of serum osmolality.
posterior pituitary
Hyponatremia, which is defined as a plasma Na + concentration _____ mM, is a very common disorder, occurring in up to 22% of hospitalized patients
<135
Hypovolemia causes a marked neurohumoral activation, increasing circulating levels of ____.
AVP
The increase in circulating AVP helps preserve blood pressure via ____receptors and increases water reabsorption via ____receptors;
vascular and baroreceptor V 1A
renal V 2
Nonrenal cause of hypovolemic hyponatremia
gastrointestinal loss (e.g., v iting, diarrhea, tube drainage) and insensible loss (sweating, burns)
Urine Na conc of nonrenal hypovolemic hyponatremia
Urine Na <20mM
Renal cause of hypovolemic hyponatremia Urine Na
> 20mM
A deficiency in circulating ____ and/or its renal effects can lead to hyponatremia in primary adrenal insufficiency a
aldosterone
Hyperkalemia and hyponatremia in a hypotensive and/or hypovolemic patient with high urine Na + concentration (much greater than 20 mM) should strongly suggest this diagnosis
Primary Adrenal Insufficiency
_____ diuretics cause hyponatremia via a number of mechanisms, including polydipsia and diuretic-induced volume depletion. These diuretics do not inhibit renal concentrating mechanism.
Thiazide
_____ diuretics, which are less frequently associated with hyponatremia, inhibit Na+ -Cl – and K + absorption by the TALH, blunting the countercurrent mechanism and reducing the ability to concentrate the urine.
loop diuretics
A rare cause of hypovolemic hyponatremia, encompassing hyponatremia with clinical hypovolemia and inappropriate natriuresis in association with intracranial disease; associated disorders include subarachnoid hemorrhage, traumatic brain injury, craniotomy, encephalitis, and meningitis.
Cerebral Salt wasting
______ responds to Na⁺-Cl⁻ repletion, while ___ does not
Cerebral salt wasting
SIADH
Patients with _____develop an increase in total-body Na+ -Cl – that is accompanied by a proportionately greater increase in total-body water, leading to a reduced plasma Na +concentration.
hypervolemic hyponatremia
Hypervolemic hyponatremia Urine Na in sodium avid edematous disorders such as CHF, cirrhosis and nephrotic sydrome
<10mM
The deficit in circulating aldosterone in primary adrenal insufficiency causes hypovolemic hyponatremia, the predominant glucocorticoid deficiency in secondary adrenal failure is associated with _____.
euvolemic hyponatremia
In secondary adrenal insufficiency due to pituitary disease glucocorticoids exert a ______ feedback on AVP release by the posterior pituitary such that hydrocortisone replacement in these patients can rapidly normalize the AVP response to osmolality, reducing circulating AVP.
negative
The _____ is the most frequent cause of euvolemic hyponatremia
SIAD
Serum uric acid is often _____ in patients with SIAD, consistent with suppressed proximal tubular transport in the setting of increased distal tubular Na+ -Cl – and water transport
low (<4 mg/dL)
Patients with hypovolemic hyponatremia will often be _____ due to a shared activation of proximal tubular Na+ -Cl – and urate transport.
hyperuricemic
SIAD also occurs with malignancies, most commonly with _____ (75% of malignancy-associated SIAD);
small-cell lung carcinoma
Classically, this occurs in alcoholics whose sole nutrient is beer, hence the diagnostic label of _____; beer is very low in protein and salt content, containing only 1–2 mM of Na+.
beer potomania
Overly rapid correction of hyponatremia (>8–10 mM in 24 h or 18 mM in 48 h) causes hypertonic stress in astrocytes within brain regions prone to ____, leading to generalized protein ubiquitination and endoplasmic reticulum stress due to activation of the unfolded protein response
ODS
However, even appropriately slow correction can be associated with ODS, particularly in patients with additional risk factors; these include _____
alcoholism, malnutrition, hypokalemia, and liver transplantation.
Relowering of plasma Na +concentration after overly rapid correction can prevent or attenuate ODS T/F
T
The coexistence of hyponatremia with a normal or increased plasma tonicity.
Pseudohyponatremia
Laboratory investigation should include a measurement of _____ to exclude pseudohyponatremia,
serum osmolality
Plasma Na +concentration_____ for every 100-mg/dL increase in glucose, due to glucose-induced water efflux from cells; this “true” hyponatremia resolves after correction of hyperglycemia.
falls by ~1.6–2.4 mM
A urine Na +concentration _____ is consistent with hypovolemic hyponatremia, in the clinical absence of a hypervolemic, Na+-avid syndrome such as CHF (Fig. 53-5)
<20–30 mM
In contrast, patients with SIAD will typically excrete urine with an Na+ concentration that is _____.
> 30 mM
The ultimate “gold standard” for the diagnosis of hypovolemic hyponatremia is the demonstration that _______.
plasma Na + concentration corrects after hydration with normal saline
Defer making a diagnosis of SIAD in patients until _____after discontinuing the thiazide.
1–2 weeks
A urine osmolality <100 mOsm/kg is suggestive of _____; urine osmolality >400 mOsm/kg indicates that ____ is playing a more dominant role, whereas intermediate values are more consistent with multifactorial pathophysiology
polydipsia
AVP excess
The measurement of _____ concentration is required to calculate the urine-to-plasma electrolyte ratio, which is useful to predict the response to fluid restriction
urine K +
Patients with chronic hyponatremia are at risk for ODS if plasma Na + concentration is corrected by _____ within the first 24 h and/or by ____ within the first 48 h.
> 8–10 mM
> 18 mM
Hypovolemic hyponatremia will respond to intravenous hydration with _____, with a rapid reduction in circulating AVP and a brisk water diuresis
isotonic normal saline
______ Hyponatremia:
Causes: SIAD, hypothyroidism, secondary adrenal failure.
Treatment: Manage the underlying cause, if reversible.
Euvolemic
______ Hyponatremia:
Treatment: Isotonic Normal Saline (0.9%)
Effect: Reduces AVP → Induces water diuresis.
Adjustment: Slow the correction if the history suggests chronicity (>48h).
Hypovolemic
_______/Low Solute Intake:
Treatment: IV Saline + Normal Diet
Risk: High ODS risk due to associated malnutrition and hypokalemia.
Beer Potomania
_____ has long been a cornerstone of the therapy of chronic hyponatremia
Water deprivation
The urine-toplasma electrolyte ratio (urinary [Na+ ] + [K+ ]/plasma [Na+ ]) can be exploited as a quick indicator of electrolyte-free water excretion; patients with a ratio of >1 should be more aggressively restricted (______) if possible
<500 mL/d
The urine-toplasma electrolyte ratio (urinary [Na+ ] + [K+ ]/plasma [Na+ ]) can be exploited as a quick indicator of electrolyte-free water excretion;
ratio of ~1 should be restricted to ____
500–700 mL/d
The urine-toplasma electrolyte ratio (urinary [Na+ ] + [K+ ]/plasma [Na+ ]) can be exploited as a quick indicator of electrolyte-free water excretion;
ratio of ratio <1 should be restricted to ______
<1 L/d
____ is a potent inhibitor of principal cells and can be used in patients whose Na levels do not increase in response to furosemide and salt tablets.
Demeclocycline
_____ are highly effective in SIAD and in hypervolemic hyponatremia due to heart failure or cirrhosis, reliably increasing plasma Na + concentration due to their “aquaretic” effects (augmentation of free water clearance).
AVP antagonists (vaptans)
_____ is perhaps most appropriate for the m agement of significant and persistent SIAD (e.g., in small-cell lung carcinoma) that has not responded to water restriction and/or oral furosemide and salt tablets.
Oral tolvaptan
Treatment of acute symptomatic hyponatremia should include ______ to acutely increase plasma Na + concentration by 1–2 mM/h to a total of 4–6 mM
hypertonic 3% saline (513 mM)
The rate of correction should be comparatively slow in chronic hyponatremia (_______), so as to avoid ODS
<6-8 mM in the first 24 h and <6 mM each subsequent 24h
Overcorrection management of hyponatremia
DDAVP
D5Water
Hypernatremia is defined as an increase in the plasma Na +concentration to _______.
> 145 mM
Hypernatremia is usually the result of a ____, with losses of H2O in excess of Na+.
combined water and electrolyte deficit
_____ individuals with reduced thirst and/or diminished access to fluids are at the highest risk of developing hypernatremia.
Elderly
_____ is a rare complication of late-term pregnancy wherein increased activity of a circulating placental protease with “vasopressinase” activity leads to reduced circulating AVP and polyuria, often accompanied by hypernatremia.
Gestational DI
____ is characterized by renal resistance to AVP, which can be partial or complete
NDI
Increased ECF Osmolality → Osmotic gradient between ECF and ICF → Water efflux from cells → Cellular shrinkage.
Hypernatremia
As in hyponatremia, the symptoms of hypernatremia are predominantly ____
neurologic
_____ is the most frequent manifestation, ranging from mild confusion and lethargy to deep coma
Altered mental status
Normal Physiologic Response to Hypernatremia:
Serum Osmolality >295 mOsm/kg → _______
Increased AVP secretion.
It is imperative to correct hypernatremia slowly to avoid ______, typically replacing the calculated free water deficit over 48 h.
cerebral edema
Depending on the history, blood pressure, or clinical volume status, it may be appropriate to initially treat with ____
hypotonic saline solutions (1/4 or 1/2 normal saline);
It must be emphasized that thiazides, amiloride, and NSAIDs are only appropriate for ______
chronic management of polyuria from NDI
Which of the following best describes the primary mechanism of hypernatremia?
A. Sodium retention exceeding water retention
B. Water loss exceeding sodium loss
C. Excessive fluid intake
D. Sodium loss without water loss
B
A 75-year-old patient presents with confusion and a serum Na⁺ of 160 mM. Which of the following conditions is the most likely cause of their hypernatremia?
A. Overhydration
B. Hypokalemia
C. Reduced thirst and fluid intake
D. Excessive sodium intake
C
Which laboratory value pattern is most consistent with osmotic diuresis due to hyperglycemia?
A. Urine osmolality >800 mOsm/kg, urine Na⁺ <20 mM
B. Urine osmolality >800 mOsm/kg, urine solute excretion >1000 mOsm/day
C. Urine osmolality <100 mOsm/kg, urine Na⁺ <10 mM
D. Urine osmolality >500 mOsm/kg, urine Na⁺ <10 mM
B
Osmotic diuresis causes excessive solute excretion (>750–1000 mOsm/day), resulting in high urine osmolality.
Which of the following most accurately differentiates central diabetes insipidus (DI) from nephrogenic DI?
A. Increased AVP levels in central DI
B. No response to desmopressin in central DI
C. Increased urine osmolality after desmopressin in central DI
D. Hyperkalemia in central DI
C
Which condition is most likely to cause nephrogenic DI through direct tubular toxicity?
A. Hypercalcemia
B. Hypokalemia
C. Lithium therapy
D. SIADH
C
What is the most appropriate initial fluid therapy for a patient with severe hypernatremia (Na⁺ >160 mM) and hypotension?
A. Normal saline (0.9%)
B. 5% Dextrose in water (D5W)
C. Half-normal saline (0.45%)
D. Oral free water
A
: In severe hypernatremia with hypotension, isotonic saline is used first to restore intravascular volume before correcting free water deficits.
What is the recommended maximum daily correction rate for chronic hypernatremia?
A. 4 mM/day
B. 6 mM/day
C. 10 mM/day
D. 12 mM/day
C
Which electrolyte abnormality is commonly associated with lithium-induced nephrogenic DI?
A. Hypernatremia
B. Hyperkalemia
C. Hypercalcemia
D. Hypokalemia
A
Which finding confirms a diagnosis of central DI?
A. High AVP with high serum Na⁺
B. Increased urine osmolality after DDAVP
C. Urine osmolality >800 mOsm/kg at baseline
D. Low serum osmolality with low urine output
B
Which of the following is the preferred fluid for free water replacement in hypernatremia?
A. D5W (5% dextrose in water)
B. Lactated Ringer’s
C. Half-normal saline (0.45%)
D. Normal saline (0.9%)
A
A 70-year-old patient with a serum Na⁺ of 165 mM is receiving D5W. After 12 hours, their serum Na⁺ has dropped by 14 mM. What is the next appropriate step?
A. Continue D5W infusion at the same rate
B. Stop D5W and monitor serum Na⁺
C. Slow the infusion rate to prevent overcorrection
D. Switch to normal saline
C
Correcting hypernatremia too rapidly (>10 mM/day) increases the risk of cerebral edema.
A patient with hypernatremia is found to have an increased ECF volume. Which of the following is the most likely cause?
A. Insensible water loss
B. Hypertonic sodium bicarbonate administration
C. Central diabetes insipidus
D. Gastrointestinal water loss
B
In a patient with hypernatremia and polyuria, the urine osmolality is measured and found to be <300 mOsm/kg. After administration of desmopressin (DDAVP), the urine osmolality increases by >50%. What is the most likely diagnosis?
A. Central diabetes insipidus
B. Nephrogenic diabetes insipidus
C. Osmotic diuresis
D. Insensible water loss
A
A patient with hypernatremia and an ECF volume that is not increased is found to have a urine osmolality >750 mOsm/day. Which of the following is the most likely cause?
A. Insensible water loss
B. Osmotic diuresis
C. Central diabetes insipidus
D. Nephrogenic diabetes insipidus
B
In a patient with hypernatremia, desmopressin is administered. The urine osmolality does not increase, and serum AVP levels are elevated. What is the most likely diagnosis?
A. Central diabetes insipidus
B. Nephrogenic diabetes insipidus
C. Insensible water loss
D. Gastrointestinal water loss
B
