Fluid and Electrolyte Disorders by Marc Imhotep Cray, M.D.

Fluid and Electrolyte Disorders Marc 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 Marc 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

Marc Imhotep Cray, MD

Hyponatremia ď ą 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

Marc 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

Marc 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

Marc 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

Marc Imhotep Cray, MD

Hyponatremia (5) ď&#x201A;§ Examples of hypovolemic hyponatremia include o hypotonic fluid loss (diarrhea, sweating, and respiration)ď&#x192; 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)

Marc 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) Marc 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

Marc 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

Marc Imhotep Cray, MD

Limited solute intake (poor oral intake as in alcoholics [“beer potomania”] or “tea and toast diet”) limits ability of kidneys to excrete free water

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

Marc 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 Marc 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

Marc Imhotep Cray, MD

Hyponatremia (12) ď ą 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

Marc 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 Marc 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 Marc 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

Marc 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 Marc 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. Marc 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 Marc 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

Marc 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)

Marc 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+ Marc 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

Marc 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+)

Marc 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) Marc 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

Marc 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) Marc 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 ď ś Rationale for each followsâ&#x20AC;Ś Marc 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. Marc 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

Marc 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

ď śDiscussion of each followsâ&#x20AC;Ś Marc 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+ Marc 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

Marc 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

Marc Imhotep Cray, MD

Hypokalemia (5) Treatment: ď ą K+ repletion and correction of underlying cause ď ą 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

Marc 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

Marc 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… Marc 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 Marc 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 510% 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

Marc 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 Marc Imhotep Cray, MD

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

Marc Imhotep Cray, MD