pathophysiology chapter 24

CHAPTER 24

FLUID AND ELECTROLYTE HOMEOSTASIS

AND IMBALANCES

INTRODUCTION• The fluid of the body flows in arteries,

veins, and lymph vessels• Body fluids are secreted into specialized

compartments• Joints• Cerebral ventricle• Intestinal lumen

FUNCTION OF BODY FLUID• Surrounds and permeates the cells• Lubricant and solvent for metabolic

chemical reactions• Transports oxygen, nutrients, chemical

messengers, and waste products to their destinations

• Important in regulating body temperature

ABNORMALITIES IN BODY FLUID

• Can occur in:• Volume• Concentration• Electrolyte composition of body fluid

• Can cause clinical problems or death• Occur as a result of many different

pathophysiologic conditions

BODY FLUID HOMEOSTASIS• Important terminology

• Body fluid• Extracellular fluid• Intracellular fluid

BODY FLUID• Pertains to water within the body and the

particles dissolved in it

EXTRACELLULAR FLUID• Contained outside the cells

• Interstitial compartment (between cells)• Relatively rich in sodium, chloride, bicarbonate ions,

and proteins• Relatively low in potassium, magnesium, and

phosphate ions• Vascular compartment (in blood vessels)

• Also relatively rich in proteins• Dense connective tissue and bone• Other compartments (synovial, cerebrospinal, GI

fluids)

INTRACELLULAR FLUID• Contained inside the cells

• Relatively rich in potassium and magnesium ions, inorganic and organic phosphates, andproteins

• Relatively low in sodium and chloride ions

TOTAL BODY WATER• Total of the water in all fluid compartments• Percentage of body weight that is water

varies• According to a person’s age• In proportion to body fat

• See Figure 24-2

0102030405060708090

1st Qtr 2nd Qtr 3rd Qtr 4th Qtr

EastWestNorth

FLUID HOMEOSTASIS• Dynamic process results from interplay of

four sub-processes• Fluid intake• Fluid absorption• Fluid distribution• Fluid excretion

• See Figure 24-3

FLUID INTAKE• Fluid intake is entry of fluid into the body by

any route• Healthy people ingest fluids orally

• Drinking• Eating (water contained in food)

• Small amount of water synthesized through cellular metabolism

FLUID INTAKE (CONT.)• Influenced by:

• Habit• Social factors• Thirst triggered by:

• Increased concentration of extracellular fluid • Decreased circulating blood volume • Dryness of mucous membranes of mouth• Possibly other visceral signals

• In older adults, thirst diminishes; they may have insufficient fluid intake

OTHER POSSIBLE ROUTES OF INTAKE

• Controlled by health professionals• Intravenous intake• Intake tubes in GI tract and other body cavities• Subcutaneous tissue or bone marrow infusion• Rectal intake (tap water enema)

• Accidental• Lungs (near-drowning)

FLUID DISTRIBUTION• Vascular fluid distribution

• Much fluid within vascular compartment distributes into other fluid compartments

• Net result of filtration across permeable capillaries (capillary forces)

CAPILLARY FORCES• Move fluid from capillaries into interstitial

compartment• Capillary hydrostatic pressure: outward push of

vascular fluid against capillary walls• Interstitial fluid osmotic pressure: inward-pulling

force of particles in the interstitial fluid• Move fluid from interstitial compartment

into capillaries• Capillary osmotic pressure: inward-pulling force of

particles in vascular fluid

CAPILLARY FORCES (CONT.)• Interstitial hydrostatic pressure: outward push of

interstitial fluid against outside of capillary walls• See Figure 24-1

FIGURE 24-1

INTERSTITIAL AND INTRACELLULAR

FLUID DISTRIBUTION• Fluid distribution between the vascular and

interstitial compartments is net result of differences in particle concentration (osmolality)

OSMOLALITY AND OSMOSIS• Cell membranes are permeable to water

but not to electrolytes• Water crosses the cell membrane rapidly to

equalize particle concentration inside and outside the cells (osmosis)

DIRECTION OF WATER MOVEMENT

• Determined by the particle concentrations on the two sides of the semipermeable cell membrane

• Changes in the osmolality of the interstitial and intracellular compartments control the distribution of water between them

WATER MOVEMENT OUT OF CELLS

• Occurs when particle concentration (osmolality) of the interstitial fluid becomes higher than the particle concentration inside cells

• Water moves from the cells to the interstitial fluid to equalize the osmolality in the two compartments

WATER MOVEMENT INTO CELLS• Occurs when the osmolality of the

interstitial fluid becomes lower than the osmolality of the intracellular fluid

• Water moves from the interstitial compartment to the intracellular compartment to equalize the osmolality

FLUID EXCRETION• Occurs through:

• Urinary tract• Largest volume excreted

• Bowels• Normal bowel function• Increases with diarrhea

• Lungs• Exhalation

• Skin• Visible sweat• Insensible perspiration

URINE• Amount of fluid excreted in the urine is

controlled primarily by hormones• Antidiuretic hormone (ADH)• Aldosterone• Natriuretic peptides (ANP and BNP)• Other minor hormones

SECRETION AND RELEASE OF ADH

• Synthesized by cells in the supraoptic and paraventricular nuclei of the hypothalamus

• Release of ADH occurs from the posterior pituitary gland

• Factors that increase release of ADH into the blood include increased osmolality (concentration) of the extracellularfluid, decreased circulating fluid volume, pain, nausea, and physiologic and psychological stressors.

FUNCTION OF ADH• Causes reabsorption of water, which:

• Decreases urine volume• Makes urine more concentrated• Decreases fluid excretion• Concentrates the urine thus decreasing fluid

excretion• If ADH release is decreased, result is large

dilute urine volume• Decreased osmolality of extracellular fluid• Ethanol intake

ALDOSTERONE• Synthesized and secreted by cells in the

adrenal cortex• Major stimulus for its release

• Angiotensin I• From the renin-angiotensin system• Activated by decreased circulating blood volume and

increased concentration of potassium ions in the plasma

FUNCTION OF ALDOSTERONE• Causes renal tubules to reabsorb sodium

and water (saline)• Decreases fluid excretion, although by a

different mechanism than ADH• When more aldosterone is secreted, urine

volume is smaller; decreased secretion ofaldosterone causes a larger urine volume

COMPARISON OF ADH AND ALDOSTERONE

• ADH is the tap water hormone• Causes the kidneys to reabsorb water• Renal reabsorption of water due to ADH makes a

smaller volume of more concentratedurine

• Aldosterone is the saltwater hormone• Causes the kidneys to reabsorb sodium and water• Renal reabsorption of sodium and water due to

aldosterone makes a smaller volume of urine

ANP • Normally secreted from cells in the heart

when the atria are stretched

BNP• B-type natriuretic peptide• Released from ventricular cells when

ventricular diastolic pressureincreases abnormally, as in heart failure

FUNCTION OF ANP AND BNP• Promote fluid excretion in the urine by:

• Causing natriuresis (sodium excretion in the urine)• Sodium excretion is accompanied by water

excretion

REGULATION OF NPS• When vascular volume increases:

• Heart is stretched• More NPs released to cause renal excretion of the

excess• When vascular volume is decreased:

• Heart is less stretched• Fewer NPs released• Kidneys excrete less fluid

• NPs oppose the action of aldosterone, but they are not as strong as aldosterone

ADEQUATE URINE VOLUME• Highly dependent on:

• Adequate blood pressure to perfuse the kidneys• Glomerular filtration rate (GFR)

ABNORMAL FLUID LOSS• May be a significant factor in disturbing

fluid status• Types of abnormal fluid loss

• Emesis• Tubes in the GI tract or other body cavities• Hemorrhage• Drainage from fistulas, wounds, or open skin• Paracentesis

CATEGORIES OF FLUID IMBALANCES

• Extracellular (saline) imbalances• Imbalances of body fluid (water)

concentration• Extracellular and body fluid imbalances can

occur simultaneously• Both volume and serum sodium concentration are

abnormal

EXTRACELLULAR FLUID IMBALANCES

• Too much or too little extracellular fluid• Involve a change in the amount or volume

of extracellular fluid• Also termed saline imbalances because

they are disorders of isotonic salt water (in the same concentration as the normal plasma concentration)

• May lead to hypovolemic shock, which can be fatal if not treated effectively (fluid replacement)

VOLUME DEFICIT• Caused by removal of a sodium-containing

fluid from the body• Decrease in saline in the same

concentration as normal extracellular fluid• Condition sometimes termed saline deficit

UNCOMPLICATED VOLUME DEFICIT

• Serum sodium concentration is normal• Concentration of extracellular fluid is

normal• Amount of extracellular fluid is abnormally

decreased• See Figure 24-4

FIGURE 24-4

ETIOLOGY OF VOLUME DEFICIT• Removal of a sodium-containing fluid from

the extracellular compartment• Usually fluid is removed from body• In some instances, fluid is sequestered in a “third

space” in the body, outside the extracellular compartment• Example: ascites, fluid in the peritoneal cavity• If this develops rapidly, may deplete extracellular

volume

CLINICAL MANIFESTATIONS• Sudden weight loss• Postural blood

pressure decrease with concurrent increased heart rate

• Flat neck veins (or veins collapsing with inspiration) when a patient is supine

• Prolonged small vein filling time

• Prolonged capillary refill time

• Lightheadedness• Dizziness• Syncope• Oliguria or small

volume of concentrated urine (if kidneys are responding normally)

OTHER CLINICAL MANIFESTATIONS

• Decreased skin turgor• Dryness of oral

mucous membranes between cheek and gum

• Hard stools• Soft sunken eyeballs• Longitudinal furrows

in the tongue• Absence of tears and

sweat

• In infants• Fontanel may be

sunken• Neck veins are not

reliably assessed in infants

WEIGHT LOSS• Sudden weight loss is a sensitive measure

of ECV deficit• One liter of saline weighs 1 kg• A person who loses 1 kg in 24 hours has excreted

1 L of fluid or lost it through an abnormal route

THIRD SPACE SEQUESTRATION• ECV deficit may occur without a weight loss

if fluid is sequestered in a third space somewhere in the body, as with ascites or intestinal obstruction

• Can be detected with shifts in orthostatic blood pressure

EXTRACELLULAR VOLUME EXCESS

• Opposite of extracellular volume deficit• Amount of extracellular fluid is abnormally

increased• Vascular and interstitial areas have too

much fluid• See Figure 24-5

UNCOMPLICATED ECV EXCESS• Concentration of extracellular fluid is

normal• Excessive amount of that fluid is present

ETIOLOGY• Caused by addition or retention of isotonic

saline; sometimes termed saline excess• Hormone aldosterone causes kidneys to

retain saline; therefore, ECV excess may be caused by conditions that involve excessive aldosterone secretion• Compensatory mechanism that can accompany

chronic heart failure

CAUSES OF EXTRACELLULAR FLUID VOLUME EXCESS

• Excessive intravenous infusion of sodium-containing isotonic solutions• Normal saline (0.9%

sodium chloride)• Ringer injection• Lactated Ringer

injection

• Renal retention of sodium and water• Primary

hyperaldosteronism• Chronic heart failure• Cirrhosis• Acute

glomerulonephritis• Chronic renal failure• Cushing disease• Corticosteroid

therapy

CLINICAL MANIFESTATIONS• Sudden weight gain:

a sensitive measure of extracellular volume excess

• Manifestations of circulatory overload• Bounding pulse• Neck vein distention

in upright position• Crackles in dependent

portions of lungs• Dyspnea• Orthopnea

• Edema• If advanced, frothy

sputum of pulmonary edema

• In infant• Bulging fontanel• Assessment of neck

veins is not effective in infants

BODY FLUID CONCENTRATION• Imbalances of body fluid concentration are

disorders of concentration and not amount of extracellular fluid

• Also called water imbalances• Serum sodium concentration reflects osmolality of

blood• Recognized by abnormal serum sodium

concentration

HYPONATREMIA

• A serum sodium concentration below the lower limit of normal

• When present the extracellular fluid contains relatively too much water for the amount of sodium ions present

• Extracellular fluid is more dilute than normal

ETIOLOGY OF HYPONATREMIA• Factors that produce a relative excess of

water in proportion to salt in the extracellular fluid

• Because serum sodium concentration reflects the osmolality of the blood, reduced serum sodium indicates that extracellular fluid has a reduced osmolality; it is too dilute

• Also called:• Hypotonic syndrome• Hypo-osmolality• Water intoxication

ETIOLOGY OF EXCESS WATER IN EXTRACELLULAR FLUID

• Excessive intravenous infusion of 5% dextrose in water (D5W)

• Hypotonic irrigating solutions• Tap water enemas• Psychogenic polydipsia (compulsive water

drinking)• Forced excessive water ingestion (child

abuse or club initiation)• Excessive beer ingestion (beer potomania)


(CONT.)• Near-drowning in fresh water• Selective serotonin reuptake inhibitors

(SSRIs)• Loss of relatively more salt than water• Diuretics, especially thiazides• Salt-wasting renal disease• Replacement of water but not salt lost

through emesis, diarrhea, gastric suction, diaphoresis, or burns


(CONT.)• Abnormal concentration of extracellular

fluid• Results when normal proportion of salt to

water in extracellular fluid is disrupted• Gain of relatively more water than salt

• ADH elevation• Causes kidneys to retain excessive amounts of

water (a gain of water relative to salt)

CAUSES OF ADH ELEVATION• The syndrome of inappropriate secretion of

ADH (SIADH)• Ectopic synthesis

• For example, small cell (oat cell) carcinoma is a type of lung tumor that frequently synthesizes and releases ADH

• Physical or psychological stressors• Pain, nausea, other symptoms

CLINICAL MANIFESTATIONS• Mild central

nervous system dysfunction• Malaise• Anorexia• Nausea• Vomiting• Headache

• Severe central nervous system dysfunction• Confusion• Lethargy• Seizures• Coma• Fatal cerebral

herniation

HYPERNATREMIA• Serum sodium concentration above upper

limit of normal• Extracellular fluid contains relatively too

little water for the amount of sodium ions present; it is too concentrated

• Also called• Water deficit• Hypertonic syndrome• Hyperosmolality

ETIOLOGY• Gain of more salt than

water• Inadequately diluted

concentrated tube feedings

• Intravenous infusion of hypertonic solution

• Near-drowning in saltwater

• Overuse of salt tablets• Food intake with

reduced fluid intake• Difficulty swallowing

fluids• No access to water• Inability to respond to

thirst

• Loss of more water than salt• Diabetes insipidus

(deficient antidiuretic hormone)

• Tube feeding (causes obligate water loss in urine)

• Osmotic diuresis• Prolonged emesis,

diarrhea or diaphoresis without water replacement

CLINICAL MANIFESTATIONS• Mild

• Thirst• Oliguria• Confusion• Lethargy

• Severe• Seizures• Coma• Death

CLINICAL DEHYDRATION• Combination of two fluid disorders

• Extracellular volume deficit• Hypernatremia• Too small a volume of fluid in the extracellular

compartment and too-concentrated body fluids• See Figure 24-8

FIGURE 24-8

ETIOLOGY• Vomiting • Diarrhea• Knowledge deficit about salt and fluid

replacement

CLINICAL MANIFESTATIONS• Sudden weight loss• Postural blood pressure

decrease with concurrent increased heart rate

• Lightheadedness, dizziness, or syncope on standing

• Flat neck veins when supine or neck veins that collapse during inspiration (older children and adults)

• Sunken fontanel (infants)

• Rapid, thready pulse

• Prolonged small-vein filling time

• Prolonged capillary refill time

CLINICAL MANIFESTATIONS (CONT.)

• Decreased skin turgor

• Dryness of oral mucous membranes

• Absence of sweat and tears

• Hard stools• Soft, sunken

eyeballs

• Longitudinal furrows in the tongue

• Thirst• Increased serum

sodium concentration• Confusion, lethargy• Coma• Hypovolemic shock

EDEMA• Edema: excess fluid in interstitial

compartment• May be a manifestation of excess extracellular

fluid volume • May also arise from other mechanisms

• Increased capillary hydrostatic pressure• Increased interstitial fluid osmotic pressure• Blockage of lymphatic drainage• Decreased capillary osmotic pressure• See Figure 24-9

FIGURE 24-9

INCREASED CAPILLARY HYDROSTATIC PRESSURE

• Caused by:• Increased extracellular fluid volume• Increased local capillary flow that accompanies

inflammation• Venous congestion

INCREASED INTERSTITIAL FLUID OSMOTIC PRESSURE

• Occurs when inflammation increases vascular permeability and proteins leak into interstitial fluid

BLOCKAGE OF LYMPHATIC DRAINAGE

• Caused by:• Tumor• Parasites• Fibrosis from radiation therapy• Surgical removal of lymph nodes

• Edema is frequently localized

DECREASED CAPILLARY OSMOTIC PRESSURE

• Occurs when plasma proteins are decreased• Malnutrition• Liver disease (decreased protein synthesis)

• Edema may be extensive

PRINCIPLES OF ELECTROLYTEHOMEOSTASIS

• Electrolytes• Ionized salts dissolved in water• Most clinically important

• Sodium• Potassium• Calcium• Magnesium• Chloride• Bicarbonate• Phosphate

TABLE 24-1

ElectrolyteElectrolyte Normal Concentration RangeNormal Concentration RangeCalcium (total)Calcium (total) 9-11 mg/dl (4.5 to 5.5 mEq/L)9-11 mg/dl (4.5 to 5.5 mEq/L)

MagnesiumMagnesium 1.5-2.5 mEq/L1.5-2.5 mEq/L

Phosphate Phosphate 2.5-4.5 mg/dl (adults and older 2.5-4.5 mg/dl (adults and older children)children)4.5-6.5 mg/dl (children)4.5-6.5 mg/dl (children)4.3-9.3 mg/dl (neonates)4.3-9.3 mg/dl (neonates)

PotassiumPotassium 3.5-5.0 mEq/L3.5-5.0 mEq/L3.9-5.9 mEq/L (neonates)3.9-5.9 mEq/L (neonates)

SodiumSodium 135-145 mEq/L135-145 mEq/L135-162 mEq/L (neonates)135-162 mEq/L (neonates)

DYNAMIC CONTROL• Concentration of an electrolyte in plasma is

different from its concentration in the cell• For body function, electrolyte concentration

must be normal in both the plasma and in the cells

• Control of electrolyte levels is dynamic• If intake of specific electrolyte increases, excretion

of that electrolyte may increase to normalize plasma levels

• Similarly, if electrolyte intake decreases, electrolytes may be redistributed into the plasma to maintain normal plasma level

MAINTENANCE OF ELECTROLYTE

CONCENTRATIONS• Four processes responsible

• Electrolyte intake• Electrolyte absorption• Electrolyte distribution• Electrolyte excretion

• Processes work together to maintain dynamic control of electrolytes within normal limits

FIGURE 24-10

ELECTROLYTE INTAKE• Intake normally

occurs orally, through food and drink

• Other routes• Oral medications

(magnesium antacids)• Intravenous fluids• Nutritional solutions

• Blood transfusions• Administration of the

electrolyte magnesium

• Tubes into body cavities• Nasogastric and GI

feeding tube• Near-drowning in

saltwater

ELECTROLYTE ABSORPTION• Essential if electrolyte is to be useful

metabolically• Depends on other factors

• Concentration gradients• Binding proteins (may increase or decrease

absorption) • pH of intestinal content• Medications• Surgical removal of portions of GI tract

ELECTROLYTE DISTRIBUTION• Influenced primarily by hormones

• Epinephrine• Insulin• Parathyroid hormone

• Certain medications also influence electrolyte distribution

• Electrolyte movement may be rapid• Shift of electrolytes from extracellular fluid into

the electrolyte pools decreases the plasma electrolyte concentration

ELECTROLYTE DISTRIBUTION (CONT.)

• Shift of electrolyte from an electrolyte pool into the extracellular fluid increases the plasma electrolyte concentration

ELECTROLYTE EXCRETION• Occurs through urine, feces, sweat• Influenced by hormones

• Other factors• Rate of renal tubular fluid flow• Medications• Diarrhea• Vomiting

ELECTROLYTE LOSS THROUGH ABNORMAL ROUTES

• Exit of electrolytes from the body through routes other than urine, feces, sweat

• May be controllable or may result from therapeutic procedures

• Alters electrolyte homeostasis• Examples

• Vomiting• Nasogastric suction• Paracentesis• Hemodialysis• Wound drainage• Fistula drainage

ELECTROLYTE IMBALANCES• Common in many pathophysiologic

conditions• May be total body imbalance or may be

imbalance in distribution within compartments

• Excess may be caused by:• Increased intake• Increased absorption• Shift into extracellular fluid

ELECTROLYTE IMBALANCES (CONT.)

• Deficit may be caused by:• Decreased intake• Decreased absorption• Increased excretion• Loss through abnormal route

PLASMA POTASSIUM• Normal concentration of potassium ions in

serum is 3.5 to 5 mEq/L (may vary slightly with different laboratories)• Higher in neonates

HYPOKALEMIA• Decreased potassium ion concentration in

extracellular fluid• Does not necessarily denote decrease in

total body potassium• May coexist with:

• Total body potassium deficit• Total body potassium excess• Normal total body potassium ion concentration

ETIOLOGY• Decreased intake• Increased excretion

DECREASED POTASSIUM INTAKE

• Anorexia• NPO (nothing by mouth) orders and

intravenous solutions without potassium• Fasting• Unbalanced diet

SHIFT OF POTASSIUM FROM EXTRACELLULAR FLUID TO

CELLS• Alkalosis• Rapid correction of acidosis• Excess insulin (e.g., during total parenteral

nutrition)• Excess β-adrenergic stimulation• Hypokalemic familial periodic paralysis

INCREASED POTASSIUM EXCRETION THROUGH

NORMAL ROUTESRenal Route• Potassium-wasting diuretics• Corticosteroid therapy• Cushing disease• Hyperaldosteronism• Excessive ingestion of black licorice

(glycyrrhizin)• Hypomagnesemia• Parenteral carbenicillin or similar agents• Amphotericin B, cisplatin, and many other

drugs

INCREASED POTASSIUM EXCRETION THROUGH

NORMAL ROUTES (CONT.)• Fecal route

• Diarrhea (includes laxative abuse)• Skin route

• Excessive diaphoresis

LOSS OF POTASSIUM THROUGH ABNORMAL ROUTES• Emesis• Gastric suction• Fistula drainage

CLINICAL MANIFESTATIONS• Altered smooth, skeletal, cardiac muscle

function• Abdominal symptoms

• Distention• Diminished bowel sounds• Paralytic ileus

• Skeletal muscle symptoms• Bilateral muscle weakness; usually begins in legs• Respiratory paralysis


• Cardiac muscle cell hyporepolarization• Ectopic beats• Alterations in conduction• Dysrhythmias may be severe enough to cause

sudden cardiac death• Polyuria

HYPERKALEMIA• Rise of serum potassium ion concentration

in the extracellular fluid • Level above 5 mEq/L (depending on lab)• Because most potassium ions are inside

cells, total body potassium may be increased or decreased depending on cause

ETIOLOGY• Increased potassium intake• Shift of potassium from cells to extracellular

fluid• Decreased potassium excretion

INCREASED POTASSIUM INTAKE• Excessive or too-rapid intravenous

potassium infusion• Insufficiently mixed intravenous potassium• Large transfusion of stored blood• Massive doses of potassium penicillin G

SHIFT OF POTASSIUM FROM CELLS TO EXTRACELLULAR

FLUID• Acidosis caused by nonorganic acids• Insufficient insulin• Crushing injury• Cytotoxic drugs (tumor lysis syndrome)• Hyperkalemic periodic paralysis• β-Adrenergic blockade and prolonged

strenuous exercise

DECREASED POTASSIUM EXCRETION

• Oliguria (such as in hypovolemia or renal failure)

• Potassium-sparing diuretics• Adrenal insufficiency• Renin-deficient states• Drugs that reduce aldosterone effects

• Angiotensin-converting enzyme (ACE) inhibitors• Angiotensin II receptor antagonists• Selective aldosterone blockers

• Nephrotoxic drugs

CLINICAL MANIFESTATIONS• Muscle dysfunction

• Early, mild• Intestinal cramping, diarrhea

• Late, more severe• Muscle weakness: ascending, beginning in lower

extremities• Cardiac dysrhythmias and even cardiac

arrest

POTASSIUM ADAPTATION• Patients who have chronic renal failure

often undergo potassium adaptation• Therefore, relatively mild symptoms at high

plasma potassium concentrations • Mechanism

• Increased aldosterone levels• Shift of potassium excretion by colon• Shift in potassium ions from extracellular fluid into

cells

PLASMA CALCIUM• Present in three forms

• Calcium ions bound to plasma proteins (such as albumin)

• Bound to small organic ions (such as citrate)• Unbound

• Only free ionized calcium is physiologically active

PLASMA CALCIUM (CONT.)Total Serum Calcium • Measures all of the calcium (bound plus

unbound)• Normal range of total serum calcium in

adults = 9 to 11 mg/dl or 4.5 to 5.5 mEq/L (may vary slightly with different laboratories)

• Unless a calcium value specifies ionized calcium, it is total calcium

PLASMA CALCIUM (CONT.)Ionized Calcium• Measures only the unbound ionized form • The normal range of ionized calcium in

adults = 4 to 5 mg/dl, about half of the total calcium (varies with different laboratories)

• Clinically significant calcium imbalances are caused by alterations in the plasma concentration of unbound ionized calcium

HYPOCALCEMIA• Serum calcium concentration drops below

the lower limit of normal• Fraction of unbound ionized calcium in the

blood by more calcium binding to plasma proteins or other organic ions• The total serum calcium may be normal• Ionized hypocalcemia is present and may cause

signs and symptoms

ETIOLOGY• Decreased calcium intake or absorption• Decreased physiologic availability of

calcium• Increased calcium excretion through normal

routes

DECREASED CALCIUM INTAKE OR ABSORPTION

• Diet with insufficient calcium and vitamin D• Chronic kidney disease (deficient activated

vitamin D)• Excessive dietary phytates or oxalates• Steatorrhea• Pancreatitis• Chronic diarrhea (includes laxative abuse)• Malabsorption syndromes

DECREASED PHYSIOLOGIC AVAILABILITY OF CALCIUM

• Hypoparathyroidism• Excessive phosphate intake• Tumor lysis syndrome (high phosphate)• Hypomagnesemia• Alkalosis• Large transfusion of citrated blood• Rapid infusion of plasma expanders that

bind calcium• Elevated plasma free fatty acids• Chronic kidney disease

INCREASED CALCIUM EXCRETION THROUGH

NORMAL ROUTES• Steatorrhea• Pancreatitis

CLINICAL MANIFESTATIONS• Alteration in normal neuromuscular

excitability resulting in: • Positive Trousseau sign• Positive Chvostek sign

• Paresthesias• Muscle twitching and cramping• Hyperactive reflexes


• Carpal spasm• Pedal spasm• Tetany• Laryngospasm• Seizures• Cardiac dysrhythmias

HYPERCALCEMIA• Increased calcium intake or absorption

• Milk-alkali syndrome• Vitamin D overdose (includes shark cartilage

supplements)

HYPERCALCEMIA (CONT.)• Shift of calcium from bone to extracellular

fluid• Hyperparathyroidism• Immobilization• Paget disease• Bone tumors• Multiple myeloma• Leukemia• Nonosseous malignancies that produce bone-

resorbing factors

HYPERCALCEMIA (CONT.)• Decreased calcium excretion

• Thiazide diuretics• Familial hypocalciuric hypercalcemia

PLASMA MAGNESIUM• Normal serum magnesium concentration =

1.5 to 2.5 mEqL (depending on lab)• Magnesium ions present in blood and bound

and unbound ionized forms• Plasma magnesium imbalances may occur

• At same time as total body magnesium imbalances

• In the absence of total body magnesium imbalances

HYPOMAGNESEMIA• Serum magnesium concentration below

the lower limit of normal (1.5 mEq/L)• Indicates a decreased magnesium

concentration of the extracellular fluid• Does not necessarily indicate a total body

magnesium deficit (although the two may occur concurrently)

DECREASED MAGNESIUM INTAKE OR ABSORPTION

• Chronic alcoholism• Malnutrition• Prolonged intravenous therapy without

magnesium• Ileal resection• Chronic diarrhea (includes laxative abuse)• Malabsorption syndromes• Steatorrhea• Pancreatitis

DECREASED PHYSIOLOGIC AVAILABILITY OF MAGNESIUM• Elevated plasma free fatty acids

INCREASED MAGNESIUM EXCRETION THROUGH

NORMAL ROUTES• Renal route

• Diabetic ketoacidosis• Chronic alcoholism• Hyperaldosteronism• Diuretic therapy• Aminoglycoside (e.g., gentamicin) toxicity• Amphotericin B, cisplatin, and many other drugs

• Fecal route• Steatorrhea• Pancreatitis

MAGNESIUM LOSS THROUGH ABNORMAL ROUTES

• Emesis• Gastric suction• Fistula drainage

CLINICAL MANIFESTATIONS• Increased neuromuscular excitability

• Insomnia• Hyperactive reflexes• Muscle cramps• Muscle twitching, grimacing • Positive Chvostek sign• Positive Trousseau sign• Nystagmus • Dysphagia • Ataxia• Tetany• Seizures


• Cardiac dysrhythmias

FIGURE 24-11

HYPERMAGNESEMIA• Serum magnesium concentration above

upper limit of normal (2.5 mEq/L, depending on lab)

• Indicates an excess of magnesium in extracellular fluid

ETIOLOGY• Increased magnesium intake or absorption

• Ingestion or aspiration of seawater• Excessive ingestion of magnesium-containing

medications (e.g., laxatives, antacids)• Excessive intravenous infusion of magnesium

• Decreased magnesium excretion• Oliguric renal failure• Adrenal insufficiency

CLINICAL MANIFESTATIONS• Depression of neuromuscular function

related to decreased release of acetylcholine at neuromuscular junctions• Decreased deep tendon reflexes• Lethargy• Hypotension• Flushing• Diaphoresis


• Drowsiness• Flaccid paralysis• Respiratory depression• Bradycardia• Cardiac dysrhythmias• Cardiac arrest

FIGURE 24-11

HYPOPHOSPHATEMIA• Present when concentration of phosphate in

plasma decreases below 2.5 mg/dl• Clinical manifestations often not observed

until severe, until concentration of phosphate less than 1 mg/dl

ETIOLOGY OF HYPOPHOSPHATEMIA

• Decreased phosphate intake or absorption• Chronic alcoholism• Chronic diarrhea• Malabsorption syndromes• Excessive or long-term use of antacids that bind

phosphate

ETIOLOGY OF HYPOPHOSPHATEMIA (CONT.)

• Shift of phosphate from extracellular fluid to cells• Refeeding after starvation (includes anorexia

nervosa)• Total parenteral nutrition• Hyperventilation (respiratory alkalosis)• Insulin• Epinephrine• Intravenous glucose, fructose, bicarbonate, or

lactate


• Increased phosphate excretion through the normal renal route• Alcohol withdrawal• Diuretic phase after extensive burns• Diabetic ketoacidosis• Diuretic therapy


• Phosphate loss through abnormal routes• Emesis• Hemodialysis

CLINICAL MANIFESTATIONS• Anorexia• Malaise• Paresthesias• Hemolysis• Diminished reflexes• Muscle aches, weakness• Respiratory failure• Confusion, stupor• Seizures• Coma• Impaired cardiac function

HYPERPHOSPHATEMIA• Increase in serum phosphate concentration

above the upper limit of normal, 4.5 mg/dl

ETIOLOGY OF HYPERPHOSPHATEMIA

• Increased phosphate intake or absorption• Overzealous phosphate therapy• Excessive use of phosphate-containing enemas or

laxatives• Shift of phosphate from cells to

extracellular fluid• Tumor lysis syndrome• Crushing injury• Rhabdomyolysis

ETIOLOGY OF HYPERPHOSPHATEMIA (CONT.)• Decreased phosphate excretion

• Chronic kidney disease• Oliguric renal failure• Adrenal insufficiency

CLINICAL MANIFESTATIONS• Increased neuromuscular excitability• If excess phosphate salts deposit in soft

tissues of areas of body where deposits are present• May cause aching and stiffness of joints• Itching• Conjunctivitis

VARIATIONS IN INFANTS• More extracellular fluid than intracellular

fluid; this proportion reverses by a few months of age

• Body weight is approximately 75% water• Percentage higher in preterm infants• Percentage of body weight that is water decreases

as the child grows older

INFANT VARIATIONS• Loss of fluid equivalent to 5%-10% of body

weight within first few days after birth is part of normal adjustment to extrauterine life

• Neonates have high metabolic rate, thus high turnover rate of water

• Increased insensible water excretion due to:• Proportionately large body surface area• Proportionately large respiratory mucosa surface

area

INFANT VARIATIONS (CONT.)• Vasomotor immaturity• Increased skin permeability

INFANT VARIATIONS (CONT.)• Glomerular filtration rate (GFR) is lower

than in adults• Kidneys have limited ability to concentrate

urine; therefore unable to:• Excrete large load of water effectively• Conserve fluid when needed

• Communication of thirst by crying may not be understood by caregivers, resulting in dehydration

INFANT VARIATIONS (CONT.)• Assessment of extracellular volume

imbalances should focus on tension of fontanel, not on degree of filling of neckveins

• If powdered formula not properly diluted, can result in hypernatremia

• Laboratory normal ranges of electrolytes generally wider for infants than for older children or adults

ELECTROLYTE IMBALANCES IN INFANTS

• Hypocalcemia more likely if:• Resuscitation required at birth• Infant is premature

• Most reliable physical signs• Jitteriness• Hyperactive reflexes• High-pitched cry

• Hypermagnesemia more likely if mother given magnesium sulfate before birth

GERIATRIC VARIATIONS• Age-related changes result in:

• Decreased muscle mass• Increased fat in internal organs• Less body water

• About 50% of lean older man’s body weight is water• About 45% of lean older woman’s body weight is

water• Glomerular filtration rate (GFR) is lower in

older adults than in middle-aged adults

GERIATRIC VARIATIONS (CONT.)• Kidneys less able to concentrate urine, thus

less able to conserve fluid when needed• Contributes to nocturia larger volume of urine

produced at night than in younger adults• Reduced thirst response may lead to

decreased awareness of dehydration• Age-related changes mean that older adults

may have decreased skin turgor even when appropriately hydrated

GERIATRIC VARIATIONS (CONT.)• Older adults who receive tube feedings at

higher risk for hypernatremia than middle-aged adults

• Older adults absorb more magnesium from antacids and cathartics than do middle-aged adults• With age-related changes in renal excretion, older

adults who use oral magnesium laxatives or antacids regularly are at high risk for hypermagnesemia

pathophysiology chapter 24

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