The document discusses fluid and electrolyte disorders, focusing on hyponatremia and hypernatremia. It defines normal sodium concentrations and what constitutes hyponatremia and hypernatremia. Hyponatremia and hypernatremia can be caused by changes in sodium levels or water levels in the body. The document further classifies hyponatremia as hypovolemic, euvolemic, or hypervolemic based on volume status. Causes and treatments of various electrolyte disorders are discussed in detail.

1. Fluid and
Electrolyte
Disorders
Marc Imhotep Cray, MD

2. 2Marc Imhotep Cray, MD
Hyponatremia and Hypernatremia
A normal sodium concentration [Na+] is
from 135 to 145 mEq/L
 A [Na+] under 135 mEq/L is hyponatremia
 A [Na+] over 145 mEq/L is hypernatremia
 Important to consider overall volume status
of patient, as well as, whether or not this is an
acute or chronic process

3. 3Marc Imhotep Cray, MD
Hyponatremia & Hypernatremia (2)
 [Na+] is based not only on gain or loss of
sodium  but also on gain or loss of free
water disturbances in either can lead to
[Na] abnormalities
 changes in total body water are more common
 Important regulatory hormones include ADH
and aldosterone

4. 4Marc Imhotep Cray, MD
Hyponatremia
 Hyponatremia can be caused by following:
1. Net Na+ loss in excess of net free water loss
2. Net free water gain in excess of net Na+ gain
(e.g., SIADH)
3. Free water shift (pseudohyponatremia)
N.B. Severe, symptomatic hyponatremia ([Na+]
<120 mEq/L) is almost always caused by SIADH

5. 5Marc Imhotep Cray, MD
Hyponatremia (2)
Free water shift--traditionally referred to as
pseudohyponatremia observed in a
hyperosmotic hyperglycemic state 
intracellular free water shifts extracellularly
to maintain osmotic balance
 Extracellular free water shift induces a dilutional
state for Na+  hence, hyponatremia
o total body sodium, however, is not reduced hence,
term pseudohyponatremia

6. 6Marc Imhotep Cray, MD
Hyponatremia (3)
 Hyponatremia assoc. w hyperglycemia can
be corrected by control of hyperglycemia
alone
 Hyponatremia assoc. w hyperglycemia may
be corrected as follows:
 For each 100 mg/dL of Glu over normal (e.g.,
nml is ≈ 100 mg/dL), add 2.4 mEq/L of Na+ as a
correction

7. 7Marc Imhotep Cray, MD
Hyponatremia (4)
Hyponatremia can be further classified into
hypovolemic, euvolemic, or hypervolemic
 Hypovolemic hyponatremia:
 Caused by hypotonic to hypertonic fluid loss plus
concomitant pure free water or relatively hypotonic
fluid replacement
 Stated another way hypovolemic hyponatremia
occurs when pt. has lost volume and sodium, but
has lost more sodium

8. 8Marc Imhotep Cray, MD
Hyponatremia (5)
 Examples of hypovolemic hyponatremia
include
o hypotonic fluid loss (diarrhea, sweating, and
respiration) in which urine sodium would be low
(kidney trying to actively reabsorb sodium and water)
o hypertonic fluid loss (diuretics, aldosterone
insufficiency), in which urine sodium would be
high (kidney cannot reabsorb sodium or water)

9. 9Marc Imhotep Cray, MD
Hyponatremia (6)
Euvolemic hyponatremia: Usually caused by excess
free water reabsorption= SIADH
Causes of SIADH are many, including
 Malignancy
 Pulmonary or CNS lesions
 Antipsychotic, antidepressant & antiepileptic drugs
 Pain medications
 Acute nausea and vomiting
 Pain
 A classic example is a smoker w small cell carcinoma of
lung) which can secrete ADH (among other hormones)

10. 10Marc Imhotep Cray, MD
Hyponatremia (7)
 Hyponatremia caused by SIADH is considered
euvolemic--even though body is reabsorbing large
amounts of water-- b/c accumulation of volume can
stimulate intravascular pressure-sensing receptors
(baroreceptors) to induce a natriuretic effect to
enhance sodium and water excretion
 In other words ↑ ADH stimulated water reabsorption is
countered by ↓ activity of RAAS and SANS and ↑ levels of
BNP such that ECV & ECF volume are maintained near
normal

11. 11Marc Imhotep Cray, MD
Hyponatremia (8)
 Other causes of euvolemic hyponatremia include
 excessive ingestion of free water
o overwhelms maximal ability of kidneys to
excrete water
 poor oral intake
o caused by need of kidneys to pull out solutes
w free water excretion
o Limited solute intake (poor oral intake as in alcoholics
[“beer potomania”] or “tea and toast diet”) limits ability
of kidneys to excrete free water

12. 12Marc Imhotep Cray, MD
Hyponatremia (9)
 Euvolemic hyponatremia cont’d…
difference betw. SIADH and others causes
 with SIADH, urine will be concentrated
(reabsorbed all water), but
 urine will be dilute in other conditions
 Additional causes of euvolemic hyponatremia
 hypothyroidism
 hypocortisolism
 nephrogenic syndrome of inappropriate diuresis

13. 13Marc Imhotep Cray, MD
Hyponatremia (10)
 Hypervolemic hyponatremia:
hypervolemia is caused by volume overload
from…
 Heart failure
 Liver failure (cirrhosis)
 Kidney failure or
 Hypoalbuminemia (nephrotic syndrome)
…leading to interstitial fluid overload

14. 14Marc Imhotep Cray, MD
Hyponatremia (11)
Acute hyponatremia results in ↓ osmoles
in intravascular space leading to water
rushing into cells (osmotic gradient)
 This precipitates cellular swelling and
cerebral edema leading to altered mental
status, headache, vomiting, and seizures

15. 15Marc Imhotep Cray, MD
Hyponatremia (12)
 Tx of hyponatremia can involve following:
1. Restrict water and allow kidneys to fix
problem by urinating out excess water,
2. Give salt-containing fluids IV or sodium
tablets to correct sodium, or
3. Give medications (e.g., ADH receptor
antagonists, vaptans, demeclocycline [ADH
antagonist]) to increase free water excretion

16. 16Marc Imhotep Cray, MD
Hyponatremia (13)
N.B. Care must be taken not to correct hyponatremia too quickly
 This is b/c w chronic hyponatremia (w ↓ intravascular osmoles)
body has made intracellular adjustments to fewer osmoles
 increasing osmoles in bloodstream rapidly by introducing a large
sodium load from IV fluids will pull water out of cells b/c of osmotic
gradient
 This pull of water out of cells is particularly destructive to
myelin potentially causing a syndrome called osmotic
demyelinating syndrome (ODS) [previously called central pontine
myelinolysis (CPM) ] may cause permanent neurologic
damage or death

17. 17Marc Imhotep Cray, MD
Hypernatremia
Hypernatremia can occur from following:
1. Gain of sodium
2. Loss of free water (more common), or less commonly
3. Intracellular free water shift
 It’s not intuitive loss of water could cause hypernatremia
“Wouldn’t people just drink water?”
 That’s true and is why hypernatremia is often seen
in those w altered mental status (e.g., nursing home
pts.) or intubated patients  people who cannot get
access to free water

18. 18Marc Imhotep Cray, MD
Hypernatremia (2)
 Another way to lose water is to have
diabetes insipidus (DI) causes
polyuria of very dilute urine
 Sx of hypernatremia include altered
mental status and coma
 DDx of central DI vs nephrogenic DI follows

19. 19Marc Imhotep Cray, MD
Hypernatremia (3)
In central DI problem is centrally
located in posterior pituitary gland
 If PP fails to secrete ADH
hypernatremia will result by stopping
water reabsorption in distal nephron 
results in large loss of free water
o Cause sometimes seen after head trauma
o Tx responds to desmopressin (DDAVP/
synthetic ADH) administration

20. 20Marc Imhotep Cray, MD
Hypernatremia (4)
 Nephrogenic DI occurs when there is
a problem w receptors at kidney
level:
 there is ADH but kidney can’t use it
 can be caused by chronic lithium use,
hypokalemia, or hypercalcemia, or
mutations of ADH receptors
 Does not respond to desmopressin
admin.

21. 21Marc Imhotep Cray, MD
Hypernatremia (5)
Differentiation of two types of DI can be
done by admin. of desmopressin
 In central DI, body will respond to
desmopressin b/c problem is a lack of ADH
and not with receptor pathway
o Urine osmolarity should ↑ by 50%
 If osmolarity does not ↑ by 50%
indicates problem w kidney’s ability to
use ADH and therefore, suggests
nephrogenic DI

22. 22Marc Imhotep Cray, MD
Hypernatremia (6)
Tx of nephrogenic DI is a thiazide diuretic
(counterintuitive) but as salt and water is lost
(instead of just water) w diuretic use ↑ RAA
axis activation will cause ↑ sodium (and water)
reabsorption in earlier parts of nephron (e.g.,
upregulation of Na+/H+ exchanger in proximal tubule by
angiotensin II) leading to a net ↓ in water loss

23. 23Marc Imhotep Cray, MD
Hypernatremia (7)
If primary polydipsia thought to be in DDx
of dilute polyuria (although this causes
hyponatremia, it would also lead to dilute
urine), then fluid restriction can lead to a
diagnosis
 If patient does not take in fluids w primary
polydipsia urine will concentrate normally (not
the case w DI)

24. 24Marc Imhotep Cray, MD
Hypokalemia and Hyperkalemia
 Changes in potassium levels alter resting membrane
potential leading to abnormal cellular activity
 K+ homeostasis is controlled by kidneys, w
aldosterone being key regulatory hormone leading
to excretion of K+ in urine
 Cells also have a H+/K+ exchanger leading to
changes in K+ levels w changes in pH
 acidosis causing cells to take in H+ in exchange for putting
K+ into the bloodstream
 alkalosis causing cells to give H+ to bloodstream in
exchange for taking in K+

25. 25Marc Imhotep Cray, MD
Hyperkalemia
 Hyperkalemia is defined as K+ level
higher than 5.0 mEq/L
 Causes: Hyperkalemia can be caused by
many factors main causes involving:
1. Decreased renal excretion
2. Cell lysis, and
3. Transcellular movement

26. 26Marc Imhotep Cray, MD
Hyperkalemia (2)
 Causes of ↓ renal excretion include
 renal failure (inability to excrete K+)
 hypoaldosteronism (b/c aldosterone
causes K+ loss in urine), and
 potassium-sparing diuretic use
(prevents elimination of K+)

27. 27Marc Imhotep Cray, MD
Hyperkalemia (3)
Cell lysis such as rhabdomyolysis (skeletal
muscle breakdown) or high cell turnover,
such as in some leukemias and
lymphomas can cause hyperkalemia b/c it
is spilling intracellular K+ into bloodstream
Lysis of cells during blood draws
(hemolysis) can lead to elevated K+ of bld
sample (so it is important to keep in mind)

28. 28Marc Imhotep Cray, MD
Hyperkalemia (4)
 Transcellular movement of K+, as noted,
can occur w acidosis, as excess H+ in
blood moves into cells in exchange for K+
b/c insulin and sympathetic drive both
activate Na+/K+ ATPases in cells
(promoting K+ uptake in cells)
 loss of either of these can cause hyperkalemia

29. 29Marc Imhotep Cray, MD
Hyperkalemia (5)
Clinical Findings:
 Electrocardiographic (ECG) findings include peaked
T waves (from vigorous accelerated repolarization), PR
interval prolongation, QRS widening, and eventually
a sinusoidal tracing
 Ventricular arrhythmias can also occur from abnormal
excitability of the heart
 Muscle weakness can occur b/c of higher resting
membrane potential leading to sodium channels not
being able to reset fully (repolarization not complete)

30. 30Marc Imhotep Cray, MD
Hyperkalemia (6)
Treatment:
Tx is threefold:
1.Reduce myocardial irritability to prevent
arrhythmia and death;
2.Move potassium intracellularly to temporarily
reduce potassium, and
3.Promote potassium loss through the urine and
stool
 Rationale for each follows…

31. 31Marc Imhotep Cray, MD
Hyperkalemia (7)
Reduction of myocardial irritability is via
calcium administration, which helps stabilize
cell membranes
Potassium can be moved intracellularly by
increasing Na+/K+ ATPase activity via insulin
(and glucose, to prevent hypoglycemia) and
sympathetic stimulation (usually albuterol) or
 by causing an alkalosis and promoting H+/K+
exchange across cell via bicarbonate admin.

32. 32Marc Imhotep Cray, MD
Hyperkalemia (8)
Finally, potassium must eventually be
removed from body, usually via
 potassium wasting diuretics (e.g., furosemide)
 potassium-binding resins that bind K+ in
intestines (sodium polystyrene sulfonate
[Kayexalate]) or
 dialysis

33. 33Marc Imhotep Cray, MD
Hypokalemia
Hypokalemia is defined as K+ level
less than 3.5 mEq/L
Causes: in general, are opposite of causes of
hyperkalemia, and involve:
1. Increased renal excretion
2. Transcellular movement
3. Gastrointestinal loss
Discussion of each follows…

34. 34Marc Imhotep Cray, MD
Hypokalemia (2)
Increased renal excretion is seen w
 hyperaldosteronism from any cause
 hypercortisolism b/c high levels of cortisol can
act on aldosterone receptor, and
 potassium-wasting diuretic use
 Hypokalemia can also be seen in states of ↑
diuresis, such as in DM from glucosuria leading to
polyuria
Transcellular movement
 Hypokalemia can be seen w alkalosis b/c cells
give up some H+ to help replenish lost serum H+ &
exchange it by taking in K+

35. 35Marc Imhotep Cray, MD
Hypokalemia (3)
Gastrointestinal loss
 GI fluids are generally K+-rich (stomach
acid and stool) so vomiting and
diarrhea can lead to K+ loss further
exacerbated by volume loss, leading to
RAA axis stimulation and ↑ K+ loss via
aldosterone action

36. 36Marc Imhotep Cray, MD
Hypokalemia (4)
Clinical Findings:
 Electrocardiographic (ECG) findings include
 presence of a U wave (a small hump after T
wave), and altered membrane potentials
 can also lead to arrhythmias w hypokalemia
 muscle weakness caused by a more negative
membrane resting potential
o Note: hypokalemia or hyperkalemia causes muscle
weakness

37. 37Marc Imhotep Cray, MD
Hypokalemia (5)
Treatment:
 K+ repletion and correction of underlying cause
 Avoid alkalinization and use of glucose or insulin
in patients with severe hypokalemia b/c both of
these can increase intracellular K+ uptake and
exacerbate existing hypokalemia

38. 38Marc Imhotep Cray, MD
Volume Disorders
Overview:
 The two forms of volume disorders, volume
depletion and volume excess, will be discussed
below, followed by details regarding laboratory
distinction of the two disorders
 First, however, we will review 2 important concepts
in renal physiology
 ECF volume regulation by kidneys and
 ECF volume regulation by ADH

39. 39Marc Imhotep Cray, MD
How do kidneys regulate
extracellular fluid volume?
Kidneys regulate ECF volume by adjusting rate of
excretion of Na+
In contrast,
Kidneys regulate body fluid osmolarity and sodium
conc. by altering excretion of free water (=ADH)
NB: This is one of most important concepts in renal
physiology
 In normal state, volume is regulated through sodium
balance, whereas osmolarity and sodium conc. are
regulated through water balance…

40. 40Marc Imhotep Cray, MD
Kidneys regulating ECF volume cont’d.
…Thus, it is effective circulating volume (ECV)
that is regulated by body, not ECF volume
b/c body has no way to directly follow ECF volume
levels
 Instead, various pressure and volume sensors
located throughout circulatory system (in atria,
aortic arch, carotid sinus, and afferent arterioles of
kidney) monitor ECV  and, through various
mechanisms, stimulate or inhibit Na+ excretion
o RAAS is most important
 ECV is proportional to ECF  notable exceptions
occur during CHF cirrhosis, and nephrotic syndrome

41. 41Marc Imhotep Cray, MD
How does ADH regulate ECF volume?
Under normal conditions, ADH does not work to
regulate ECF volume
 Instead, ADH normally functions to regulate reabsorption of free
water in collecting duct in response to changes in body fluid
osmolarity
 However, when ECV is severely compromised (↓ by 5-
10% of normal) secretion of ADH by posterior pituitary
is stimulated
 Thus, w significant hypovolemia, function of ADH changes to
help preserve volume rather than osmolarity

42. 42Marc Imhotep Cray, MD
ADH regulating ECF volume cont’d.
Ability of ADH to sacrifice osmolarity to help maintain
ECV is an exception to rule given above stating 
(ie. water balance is regulated to maintain osmolarity and
sodium balance is regulated to maintain volume)
 When volume is low enough, body abandons rule and
retains sodium and water regardless of osmolarity
o Illustrated by CHF, nephrotic syndrome, and
cirrhosis b/c these three diseases are have ↓ ECV,
hyponatremia commonly occurs in all of them as a
result of chronically high ADH levels

43. 43Marc Imhotep Cray, MD
Volume Depletion
Clinical presentation
 In mild volume depletion: Orthostatic
dizziness and tachycardia
 In severe volume depletion: Hypotension,
mental obtundation, cool extremities, severe
oliguria
N.B. Oliguria is earliest and most sensitive
clinical indication of hypovolemia

44. 44Marc Imhotep Cray, MD
Volume Depletion (2)
Causes of volume depletion
GI causes of volume depletion: bleeding,
vomiting, diarrhea
Renal causes of volume depletion
o Due to loss of salt and water: Diuretics, acute tubular
necrosis
o Due to loss of water: Diabetes insipidus
Skin and respiratory causes of volume
depletion: sweat, burns

45. 45Marc Imhotep Cray, MD
Causes of Volume Excess
Primary renal sodium retention (assoc. w ↑ ECV):
 Acute renal failure
 Cushing syndrome
 Hyperaldosteronism
Secondary renal sodium retention:
 Heart failure
 Liver disease
 Nephrotic syndrome
 In these edematous states, excess volume is sequestered
outside arterial system causes a persistent low-volume
stimulus to which kidney responds by retaining water,
leading to hyponatremia

46. 46Marc Imhotep Cray, MD
Laboratory studies to help determine
cause of volume disorder
1. Urine osmolality
 Increased in: Addison disease, congestive heart
failure, shock, hypovolemia,
 Decreased in: Hyperaldosteronism, diabetes insipidus,
excess fluid intake, renal tubular necrosis
2. Serum osmolality
 Increased in: Dehydration, diabetes insipidus,
increased glucose, hypernatremia, methanol
intoxication, ethylene glycol intoxication, and uremia.
 Decreased in: Excess fluid intake, hyponatremia,
SIADH

47. 47Marc Imhotep Cray, MD
Further Study
 Fluid and Electrolytes_ SDL Tutorial (Darrow-Yannet Diagrams)
 Electrolyte and Acid-Base Practice Q&A
Textbook:
Kamel KS, Halperin ML. Fluid, Electrolyte, and Acid-Base
Physiology: A Problem-Based Approach, 5th Ed. Philadelphia, PA:
Elsevier, 2017.