Fluid and Electrolyte Imbalance
Jianzhong Sheng MD, PhD
Water
Body fluids
• Extracellular fluids (ECF)
– Interstitial fluid - fills the spaces between most
cells of the body
– Intravascular fluid - plasma (WBC, RBC and
platelets in this fluid)
Body fluids
• Intracellular fluids (ICF)
– Liquids within cell membranes
– 40% of body weight
Components in body fluids
• Electrolyte
– an element that when dissolved can carry an
electrical current
– Cations - (+) ; Anions - (-)
– neuromuscular function
– acid-base balance
– ingested compounds
– serve as catalysts in nerve response, muscle
contraction, and metabolism of nutrients in
foods, regulate electrolyte balance
Movement of body fluids
• Diffusion
– Area of higher concentration to an area of
lower concentration till even distribution
• Osmosis
– Movement of a pure solvent, e.g. water
through a semipermeable membrane from a
solution that has a lower solute concentration
to one that has a higher solute concentration
Osmotic pressure
• Drawing power of water (dependent on
the number or molecules in solution)
– Isotonic
– Hypotonic
– Hypertonic
Movement of body fluids
• Filtration
– Water and diffusible substances move
together in response to fluid pressure
• Active transport
– Requires energy
– Able to move larger molecules and go from
less to greater concentration
Transmembrane water permeability
Bilayer Diffusion
Aquaporin Water Channels
Hard to explain
All biological membranes
Renal tubules, secretory glands, red cells
Low capacity
High capacity for H2O, not H3O+
Bi-directional
Directed by osmotic gradients
Unknown inhibitors
Reversibly inhibited by Hg++
Discovery of Aquaporin-1
A serendipitous observation
Contaminant in 32 kDa
Rh preparations
Simple purification
Atypical staining
Insoluble in N-lauroylsarc.
200,000 copies per red cell
Channel-like homotetramer
Protein sequence 1-35 aa
Denker et al., J Biol Chem, 1988
Smith & Agre, J Biol Chem, 1991
Discovery of Aquaporins-AQP1
Functional expression (with Wm. Guggino at JHMI)
Hypo-osmolar swelling
Hg++ inhibited, no currents
Xenopus oocyte, CHIP28
Preston et al., Science 1992
Peter Agre & Roderick MacKinnon
Nobel Prize---10 December 2003
Structure of AQP1
Hg++ inhibitory site
Fluid Intake
• Hypothalamus - thirst control center
• Oral fluid intake - requires an alert state
• Osmoreceptors - monitor osmolality
Fluid Output
• Loss through the kidneys and GI tract
• Insensible
• Sensible
Cations
• Sodium (Na+)
– Most abundant in the extracellular fluid
– Maintains water balance, transmits nerve
impulses, contracts muscles
– Values - 135-145 mEq/L
Cations
• Potassium (K+)
– Major intracellular cation
– Regulates neuromuscular excitability,
muscular contraction, and acid-base
– Value - 3.5 -5.3 mEq/L
Cations
• Calcium (Ca2+)
– Cardiac conduction, blood coagulation, bone
growth and formation, & muscular relaxation
– Value - 4 - 5 mEq/L
Cations
• Magnesium (Mg2+)
– Second most important of intracellular fluids
– Enzyme activities, muscular excitability
– Value - 1.5 - 2.5 mEq/L
Water (and sodium) disorders
Dehydration
hypertonic
isotonic
water excess
hypotonic
Extracellular fluid deficit
1. Hypotonic dehydration
sodium loss ＞ water loss
serum sodium ＜ 130mmol/L
plasma osmotic pressure ＜ 280mOsm/L
hypertonic
isotonic
hypotonic
1) Cause and Pathogenesis
Excessive loss of water
Sodium replaced with water only.
Vomiting, diarrhea; burn; diuretics;
Addison’s disease (ADS ) ;
Chronic renal failure; renal tubular acidosis
2) Adaptive response and effect on body
① movement of body fluid
ECF
ICF Cellular swelling
Blood volume
Extracellular fluid
Shock Dehydrated signs Brain and lung edema
② urinary alteration
urine specific urine
volume gravity [Na+]
---------------------------------------------------------Early ADH
±or
stage ADS
Late ADH
stage ADS
-----------------------------------------------------------
3) principles of treatment
① treating primary disease
② 0.9%NaCl
2. Hypertonic dehydration
① water loss ＞ sodium loss
② serum sodium ＞ 150mmol/L
③ plasma osmotic pressure
＞310mOsm/L
1) Cause and pathogenesis
lack of water (desert; sea)
① intake
to drink inability (coma; baby)
lung: hyperpnea
(hypoxia; acidosis)
② loss
skin: fever; hyperthyroidism; sweat;
exposure to hot environment
digestive tract: vomiting; diarrhea;
baby diarrhea ([Na+]: 60mmol/L)
kidney: diabetes (ketosis);
diabetes insipidus
diuretic (mannitol; hypertonic glucose)
2) Effect on body
① hypertonic of ECF
thirst
② movement of the body fluid
ICF
ECF
cell dehydration
Brain dehydration
Sleepiness
Dehydrated fever
subarachnoid bleeding
③urinary alteration
urine
specific
urine
volume
gravity
[Na+]
---------------------------------------------------------------Early ADH
stage ADS±
Late ADH
stage ADS
----------------------------------------------------------------3) principles of treatment
Water > NaCl
3. isotonic
dehydration
① water loss ≈ sodium loss
② serum sodium = 130-150mmol/L
③ plasma osmotic pressure:280- 310mOsm/L
1) cause and pathogenesis
① vomiting; diarrhea; gastrointestinal
suction;
biliary fistula; intestinal fistula
② ascitic fluid; pleural effusion
2) effects on body
① slight thirst
② blood volume
dehydrated signs; BP
③ urinary alteration
urine
specific
urine
volume
gravity
[Na+]
-----------------------------------------------------------------Early ADH
stage ADS
Late ADH
stage ADS
-----------------------------------------------------------------3) principles of treatment
补偏低渗液；先补0.9%NaCl
Extracellular fluid excess
1. Water intoxication
water intake , total sodium ±; ECF , ICF ;
hyponatremia; Serum sodium < 130mmol/L
1) Causes
excessive water intake
renal loss (acute renal failure;
acute congestive heart failure)
2) effects on body
brain cells swelling
water moves into cells
pulmonary edema
3) principles of treatment
diuresis
2. Edema
interstitial fluid
fluid in the body cavities
hydrops
fluid in the cells
cellular edema
(1) pathogenesis
1) imbalance of exchange between intra- and
extra-body fluid (retention of water and
sodium)
basic mechanism: glomerular-tubular
imbalance
① GFR acute glomerulonephritis
heart failure
② reabsorption of proximal tubule
sympathetic nerve
filtration fraction
ANP reabsorption of water and sodium
Electrolyte Imbalances
Hyponatremia
• Defined as serum [Na+] less than 136
mEq/L
• Water shifts into cells causing cerebral
edema
• 125 mEq/L – nausea and malaise
• 120 mEq/L – headache, lethargy,
obtundation
• 115 mEq/L – seizure and coma
Hyponatremia (cont)
• 1. Assess plasma osmolality
• 2. Assess volume status of patient
– Hypervolemic, Euvolemic, Hypovolemic
• 3. Assess Urine Sodium Concentration
– Needed for definitive diagnosis, not needed for
treatment purposes
• 4. Calculate Na+ Deficit
– 0.6 x weight (kg) x (130 – plasma [Na+])
• 5. Correct at no more than 0.5mEq/L per hour or 12
mEq/L per 24 hours
Isosmotic and Hyperosmotic
Hyponatremia
– Iso and Hyperosmotic hyponatremia are due to
excessive solutes in plasma.
– Isosmotic
• Pseudohyponatremia – No treatment necessary
– Hyperlipidemia
– Hyperproteinemia
• Isotonic Infusions
– Glycine
– Mannitol
– Hyperosmotic – Treat underlying cause
• Hyperglycemia
– Each 100 mg/dl of glucose reduces [Na+] by 1.6 mEq/l
• Hypertonic Infusions
– Glycerol
– Mannitol
– Glycine
Hyposmotic Hyponatremia
• 1. Assess volume status
– Hypervolemic – cirrhosis, heart failure,
nephrotic syndrome
– Euvolemic – polydipsia, SIADH
– Hypovolemic – most common cause
• Excessive renal (diuretic) or GI (emesis, diarrhea)
losses
Treatment of Hyponatremia
• Iso or Hyperosmotic
– Correct underlying disorder
• Hyposmotic
– Iso or hypervolemic – fluid restriction
– Hypovolemic
• Asymptomatic – fluid resuscitate with isotonic
saline
• Symptomatic or plasma [Na+] less than 110 mEq/L
– Calculate Na+ deficit
– Correct at a rate no greater than 0.5 mEq/L/hour or 12
mEq/L/day
Correction of Sodium Deficit
Example: A 60 kg woman with a plasma sodium
concentration of 120mEq/L:
Sodium deficit = TBW x (130 – [Na+]p)
Sodium deficit = 0.5 x 60 x (130-120) = 300mEq
3% NaCl contains 513 mEq sodium/L
Volume of 3% NaCl needed = 300/513 = 585 mL
At 0.5 mEq/L/hr a correction of 10 mEq should be done
over 20 hours
So, 585 mL/20 hours = 29 mL/hour of 3% NaCl
Hypernatremia
• Defined as serum [Na+] greater than 146
mEq/L
• Lethargy, weakness, and irritability that
progress to seizure, coma, and death
• Usually occurs in adults with altered
mental status or no access to water
Hypernatremia (cont)
• 1. Assess volume status
• 2. Measure urine [Na+]
• 3. Calculate water deficit
– 0.6 x weight (kg) x ([Na+]/140 -1)
• 4. Correct with free water no faster than
0.5 mEq/L/hour or 12 mEq/L/day
Hypernatremia
• Hypovolemic – loss of hypotonic fluids
– Diuresis, vomiting, diarrhea
• Isovolemic – loss of free water
– Diabetes insipidus, hypodipsia
• Hypervolemic – gain of hypertonic fluids
– Hypertonic saline administration
Treatment of Hypernatremia
• Hypovolemic
– Replace the free water deficit
• Hypervolemic
– Diuretics (lasix) to excrete sodium in urine
combined with hypotonic saline for partial
volume replacement
Treatment of Hypernatremia
• Isovolemic
– Diabetes Insipidus
– Loss of hypotonic urine secondary to lack of ADH
production (central) or lack of response to ADH by
kidney (nephrogenic)
– Hallmark is hypotonic urine (200-500 mOsm/L) with
hypertonic plasma
– Treat by correcting free water deficit
– In central DI must also administer 5 – 10 units of
DDAVP Q6H to prevent ongoing free water loss
Hyperkalemia
• Defined as a serum [K+] greater than 4.6 mEq/L
• Changes in cellular transmembrane potentials can lead
to lethal cardiac arrhythmias
• Most often associated with renal impairment coupled
with exogenous K+ administration or drugs that increase
K+
• Transcellular shifts – acidosis, succinylcholine, insulin
deficiency, massive tissue destruction
• Massive blood transfusions
• Pseudohyperkalemia - Thrombocytosis, hemolysis,
leukocytosis
• Urine K+ excretion rate can be used to determine exact
cause of hyperkalemia
Hyperkalemia
• Drugs causing hyperkalemia – K+ sparing
diruetics, ACEI, NSAIDs, Heparin,
Cyclosporin, Tacrolimus, Bactrim
• EKG Changes
– 5.5 – 6.5 mEq/L – peaked T-waves
– 6.5 – 7.5 mEq/L – loss of P-waves
– > 8.0 mEq/L – widened QRS
Treatment of Hyperkalemia
• 1. If EKG changes administer 10 mL of
10% Calcium Gluconate
• 2. 1 amp D50 with 10 units IV insulin
(onset 10-20 minutes, duration 2-3 hours)
• 3. Albuterol 10 -20 mg (onset 4-5 hours,
duration 2-3 hours)
• 4. Kayexalate 15-30 g (oral onset 4-5
hours, enema onset 1 hour)
• Dialysis
Hypokalemia
• Defined as serum [K+] less than 3.6
mEq/L
• Occurs in up to 20% of hospitalized
patients
• 2.5 mEq/L – muscular weakness, myalgia
• <2.5 mEq/L – cramps, parasthesias, ileus,
tetany, rhabdomyolisis, PVCs, A-V block,
V-tach, V-fib
Hypokalemia
• Inadequate intake
• Increased excretion – diarrhea, diuretics,
alkalosis, glucocorticoids, RTA
• Transcellular shifts – beta-agonists,
theophylline, insulin, hyperthyroidism,
barium
• Replace no faster than 20 mEq/H
peripherally and 100 mEq/H centrally
Hypercalcemia
• Excess calcium
• Needs vit D for efficient absorption; most of Ca
is stored in the bones.
• Causes: bone tumors that cause bone
destruction, chemo rx release Ca from the bones;
immobilization causes loss from the bones
(usually excreted) but if kidneys can’t clear it,
hypercalcemia results, increased intake (milkalkali syndrome).
Hypercalcemia (cont)
• Clinical manif: Ca imbalances alter
neuromuscular irritability with non-specific
symptoms
– Constipation, anorexia, N/V, fatigue, skeletal muscle
weakness, confusion, lethargy.
– Renal calculi, cardiac arrhythmias
– HyperCa increases Na and K excretion leading to
polyuria and polydipsia.
– Rx: serum Ca, Ionized Ca, fluids, Lasix, steroids,
dialysis.
Hypocalcemia
• Decreased serum calcium
• Causes: decreased intake of Ca and/or Vit D
(adolescents are vulnerable d/t fad diets and the
deficit cannot be made up later, increasing risk
for osteoporosis).
– Limited exposure to sunlight, premature infants and
dark skinned people at increased risk to inadeq. Vit D
and therefore decreased Ca absorption.
– Parathyroid dysfunction, multiple transfusion (Citrate
binds Calcium), steatorrhea (as in pancreatitis and
Cystic Fibrosis) binds Calcium in the stool.
Hypocalcemia (cont)
• Clinical Manif: acute situation related to
increased muscular excitability: tetany.
+Chvostek’s Sx, + Trousseau’s Sx.
• In children: Twitching, cramping, tingling around
the mouth or fingers, carpal/pedal spasms.
• In infants: tremors, muscle twitches, brief tonicclonic seizures, CHF.
• Laryngospasm, seizures and cardiac
arrhythmias in severe situations.
Hypocalcemia (cont 2)
• In children and adolescents, chronic
hypocalcemia more common, manif. By
spontaneous fractures.
Lab tests: serum Ca; bone density study
Rx: oral and/or IV Ca, Ca rich diet
Hypermagnesemia
• Excess in Mg.
• Imbalances characterized by
neuromuscular irritability
• Causes: impaired renal function, Mag
Sulfate given perinatally to treat eclampsia,
increased use of laxatives, enemas,
antacids, IV fluid additives.
Hypermagnesemia (cont)
• Clinical Manif: decreased muscle irritability,
hypotension, bradycardia, drowsiness,
lethargy, weak or absent DTR’s.
• Rx: increase fluids, diuretics, dialysis.
Hypomagnesemia
• Decreased serum Mg.
• Stored in cells and bones
• Causes: prolonged NPO without
replacement, chronic malnutrition, chronic
diarrhea, short bowel syndrome,
malabsorption syndromes, steatorrhea,
multiple transfusions, prolonged NG Sx,
some medications.
Hypomagnesemia (cont)
• Clinical manif: increased neuromuscular
excitability (tetany). Hyperactive reflexes,
skeletal muscle cramps, twitching, tremors,
cardiac arrhythmias, seizures.
• Lab: serum Mg along with Ca and K.
• Rx: po/IV Magnesium admin and treating
underlying cause of imbalance.