Fluid, Electrolyte Balance

Fluid, Electrolyte & Acid-Base

Disorders

1. Review of key concepts:

-- Fluid homeostasis– more than blood

flow & plasma volume

-- Fluid Compartments & composition
-- Hormones and Fluid Balance

2. Interstitial Tissue, Starling Forces,

& Edema Formation

3. Fluid and Electrolyte Disorders
4. Control of pH & Acid – Base

Disorders

-- regulatory systems: Buffers, Lungs,

Kidneys

-- clinical laboratory applications

Total Body Water & Fluid

Compartments

• Fluid compartments average adult (70kg

m)

– TBW 60% of body wt. (42L)*
– ECF 20% (plasma 5% + interstitial 15% =14L)
– ICF 40% (28L)
– (transcellular spaces- CSF, synovial etc 1-2%)

• GI Tract Fluid Loss

– GI secretes 6-8L per day & reabsorbs all but

about 100ml lost with stool. Severe diarrhea
can lose large amounts

Distribution of Major Cations and

Anions

ECF*

ICF

Na+ (mEq/L)

135-145

10

K+ (mEq/L

3.5-5.0

150

Ca++ (mEq/L) 5

(.0001)**

Cl- (mEq/l)

100-107 5

HCO3- (mEq/L)

22-28

12

Phosphate (mEq/L) 2

40-95

Proteins 16

54

pH 7.4 7.1

*Ionic composition of ISF & plasma is the same as ECF,

exception plasma has more protein; ICF calcium primarily

bound-not free

Osmolality & Tonicity

• Osmolarity = osmoles/L H2O (particles

per unit volume or liter of water)

• Osmolality = osmoles/Kg H2O (particles

per unit wt of water)

• Tonicity = osmotic pressure of solutes

(effective osmoles) that cause water

movement (NaCl, glucose, KCL,) across

cell membrane. Water moves out of the

red cell (shrinks) in a hypertonic

solution.

– Although Na is the primary effective solute,

other solutes can contribute to tonicity.

Hyponatremia can occur in high, normal &

low tonicity, ie. Hypertonic hyponatremia.

Plasma Osmolality

• Normal plasma osmolality = 280-

295 mOsm/kg H2O

• 2 estimates of plasma osmolality

– plasma osm = 2x (plasma [Na+])
– plasma osm =

2(Na+) + (glucose/18) + (urea/2.8)*

*Glucose & urea in mg/dl can converted to mmol/L or mOsm/kg – gives
better estimate than using just sodium if pts with hyperglycemia or
elevated BUN (see Berne & Levy 5

th

ed)

Osmosis & Difference between

“effective” osmolality of cell and

surrounding fluid

Osmolality
=330

Osmolality
=275

285

285

(Hypertonic)

(Hypotoni
c)

Hormone Control of Volume &

Sodium

• Two primary controls of ECF

volume (water balance):

1.

Regulation of serum sodium
concentration–

Antidiuretic Hormone (ADH)

Thirst

2.

Regulation of total body sodium –

Renin-Angiotensin-Aldosterone system

(RAA)

Natriuretic Peptides (ANP & BNP)

-Hormone Control of Volume &

Sodium

• Hypothalamus & Posterior Pituitary

– Osmoreceptors in hypothalamus respond to

decrease in vascular volume & increased

osmolarity >295 mOsmols stimulate

• thirst (diminished in age)
• ADH release from PP – regulates water excretion via

change in permeability of distal tubule

• Syndrome of Inappropriate ADH (SIADH)

– High levels of ADH result in hyponatremia. Causes:

infection, neoplasms of the CNS, pulmonary

disease, operative stress.

• Diabetes Insipidus (Low ADH-dilute urine):

– Central : CNS infections, trauma, tumor
– Nephrogenic: unresponsive to ADH (drugs,

congenital)

Regulators of ADH

• Regulators of ADH

– Two major: interact

• Plasma osmolality (react to changes as small as 1%)

osmoreceptors (shrink or swell based on plasma osmol)

located in the hypothalamus.

• Volume and pressure (5-10% change in pressure is required)

of the vascular system-activated by receptors in

– Left atrium and pulmonary artery: vascular volume
– Aortic arch and carotid sinus: wall tension (arterial pressure)
– Both send signal via vagus and glossopharyngeal.

– Nausea-stimulates
– Atrial natriuretic peptide (ANP) inhibits
– Angiotensin II stimulates
– Drugs (nicotine-stimulates secretion, alcohol-

inhibits)

Berne & Levy, 2000, p 437 &
438

ADH

-Hormone Control of Volume &

Sodium

• Renin-Angiotensin --> Aldosterone (RAA)

– Controls ECF by regulating Na excretion
– Acts on distal tubules retains Na (& water)

excretes K

– Angiotensin also direct effect of Na reabsorption

in proximal tubules & enhances ADH effect

• Atrial Natriuretic Peptide (ANP) & “Brain”

Natriuretic Peptide (BNP)*

– Secreted by atrial myocytes (BNP ventricular

myocytes-marker of HF) in response to increase

venous/atrial pressure or increase blood volume

– Increase GFR, inhibits Na (water) reabsorption

in collecting ducts

– Inhibits ADH & renin release

*Baughman KL NEJM 2002 347:158-9; Levin ER et al NEJM ’98
339:321-8

Aldosterone

• Stimulates Na+

reabsorption in

the distal

tubule and

collecting duct

• Enhances Na+

reabsorption by

cells of the

thick ascending

limb of the loop

of Henle

Response to volume
depletion

ADH and Aldosterone and ANP

Response to ECF contraction

Berne & Levy, 2000 p
451

ADH and Aldosterone and ANP

Response to ECF Expansion

Berne & Levy, 2000 p
452

Control of Urine Solute

Concentration:

Age & Disease

• Normal

– Body must excrete a minimum of 1200 mOsm
– Healthy kidney can vary concentration from 40-

1400 mOsm/L

– Minimum urine volume at maximum [C] ability

=

1200/1400 kgH2O/24 hr = 857ml/24hr

(35ml/hr)

• Development, Aging & Disease

– Infant: max concentrating ability ~

600mOsmols/kg due to low ADH and immature

renal concentrating

– Elderly: renal function diminishes with age, >70

yrs ~ 900mOsmols/kg H2O

– Minimum urine volume at maximum [C]

1200/900 kgH2O/24 hr = 1300/24hr

(55ml/hr)

Capillary- Interstitial

Exchange & Edema

Normal Interstitial Tissue

• Interstitial Tissue

– Provides the “microenvironment” of the cells
– Composed of cells, water & electrolytes, ground

substances, and fibrillary elements

– Electrolytes & pH maintained in equilibrium

both with capillary-plasma & intracellular fluid

• Fibrillary elements (collagen, elastin)

produce by connective tissue cells, mainly

fibroblasts & ground substance

(glycoproteins, fibronectin). (Implications in

aging)

• Lymphatics
• Fluid Exchange Forces: Capillary & Tissue

hydrostatic & oncotic pressure- major

difference between ISF & plasma – ISF very

low in protein!*

Starling Forces acting on capillary.
(McCance)

Edema Formation

• Excess fluid within interstitial space

• Generalized: 2 or more liters excess in

the interstitial space for edema to be

clinically evident; thus patient can gain

several kgs of H2O in weight before

edema observable or palpable (pitting).

– Cardiac, renal, hepatic failure.

– Nutritional (low albumin)

• Localized: increased capillary

permeability or Hp

– inflammation, hypersensitivity, lymph/venous

obst, lymph node resection, filariasis

– Cirrhosis with accumulation in peritoneal

space (ascites)

Mechanisms of Edema

Formation

• Increased Hydrostatic P

– increased venous pressure or impaired

venous return (heart failure -HF)

• Reduced Plasma Oncotic P*

– hypoproteinemia (nephrotic syndrome-

loss, malnutrition & cirrhosis-impaired

synthesis)

• Lymphatic obstruction

– Obstruction (neoplastic, surgical)

• Sodium retention (renal, HF,

aldosteronism)

• Inflammatory (typically local)

*Role of reduced oncotic P? as edema does not always correlate with
hypoalbuminemia

Key Electrolytes

Imbalances*

• Sodium [135-145mEq/L]

– Hypernatremia >147
– Hyponatremia < 135

• Potassium [3.5-4.5]

– Hyperkalemia >5.5
– Hypokalemia < 3.5

• Calcium [8.6-10.5 mg/dl]

– Hypercalcemia >12
– Hypocalcemia <8.5

*Huether 110-116, McCance
89-102

Regulators of ADH

• Regulators of ADH

–

Two major: interact

• Plasma osmolality (react to changes as small as 1%)

osmoreceptors (shrink or swell based on plasma osmol)

located in the hypothalamus.

• Volume and pressure (5-10% change in pressure is

required) of the vascular system-activated by receptors in

– Left atrium and pulmonary artery: vascular volume
– Aortic arch and carotid sinus: wall tension (arterial pressure)
– Both send signal via vagus and glossopharyngeal.

–

Nausea-stimulates

–

Atrial natriuretic peptide (ANP) inhibits

–

Angiotensin II stimulates

–

Drugs (nicotine-stimulates secretion, alcohol-

inhibits)

Berne & Levy, 2000, p 437 &
438