WATER AND ELECTROLYTES

22/11/2014

50 to 60% of human body is water (Decrease with age)

Body Fluid Compartments

28 L

15 L

93% of plasma (5 L) volume is water and 7% is proteins.

4

Water balance IN TAKE OUT PUT

BEVERAGES = 1500 mLWATER IN FOOD = 600 mLMETABOLIC WATER= 400 mL

TOTAL = 2500 mL

URINE = 1500 mLSKIN LOSS = 500 mL(SWEAT / INSENSIBLE)LUNGS = 400 mLFECES = 100 mLTOTAL = 2500 mL

-To be in balance, the quantities of fluids and electrolytes leaving the body should be equal to the amounts taken in. - Electrolytes are molecules that release ions in water.Anything that alters the concentrations of electrolytes will also alter the concentration of water, and vice versa.

Water balance

Water balance

• Controlling input (thirst center)• Controlling out put ( ADH)• Electrolyte balance

Water balance

• Balance of Water content of ICF and ECF is controlled the osmolality between the two must be maintained. The movement of water is controlled by

– hydrostatic and – colloid osmotic pressure

Water balance

Osmolality

• Physical property of solution• Mmol/kg of solvent (plasma)• Both sensation of thirst & ADH secretion are stimulated by

hypothalamus in response to increase smolality ( it is parameter to which hypothalamus is response)

• Affected also by the Na concentration( 90% of osmotic activity is related to Na)

• Normal range 275 – 295mSm/kg– Smolality is regulated by changes in water balance – But volume is regulated by changes in Na balance

•

Regulation of smolality • Osmoreceptors in hypothalamus response to

small changes(increase) in smolality:– Sensation of thirst– consume more fluids– increasing the water content of the ECF– and decreasing the osmolality of the plasma

• increase of smolality : – ADH secretion is stimulated – Increases renal reabsorption of water

Water Depletion (Hypovolemia) • occurs in variety of diseases like diarrhea,

vomiting, fever, burns etc.– Isotonic : loss of both water and electrolytes– Dehydration : Loss of water • The loss of water increases plasma osmolality and

causes dehydration of ICF specially of CNS tissues as water moves from ICF to ECF which more dangerous than ECF dehydration & may result in coma and death in severe cases.

Response to water depletion

• Body responds with stimulation of thirst which increases the intake of water and stimulation of ADH release which increases water reabsorption from kidneys thereby restoring the water balance.

HOMEOSTATIC CORRECTION WATER DEPLETION

Regulation of body water Volume

• Kidneys – Capillary pressure forces fluid through the walls

and into the tubule– At this point H2O or electrolytes are then either

retained or excreted– The urine becomes more dilute or more

concentrated based on the needs of the body

• Controlling of both Na and water are interrelated in controlling blood volume– ADH – Renin- Angiotensin 11 – aldosterone system is

stimulated by decrease of blood volume or decrease blood pressure

Regulation of Fluid Volume

• Antidiuretic hormone (ADH)– Also called arginine vasopressin hormone (AVP)– Produced by the hypothalamus– Stored in the pituitary gland– Restores blood volume by increasing or decreasing

excretion of water – Increased osmolality or decreased blood volume

stimulates the release of ADH– Then the kidneys reabsorb water– Also may be released by stress, pain, surgery, and

some meds

Regulation of Fluid Volume

• Renin-angiotensin-aldosterone system– Renin secreted in kidney ( glomeruli)• Amount of renin produced depends on blood flow and

amount of Na in the blood• It converts angiotensinogen into angioensin 1 which

become angiotensin 11

– Produces angiotensin II (vasoconstrictor)– Angiotensin causes peripheral vasoconstriction– Angiotensin II stimulates the production of

aldosterone

Regulation of Fluid Volume, cont.

• Aldosterone– Secreted by the adrenal gland response to angiotensin II– The adrenal gland may also be stimulated by the amount

of Na and K + in the blood– Causes the kidneys to retain Na and H2O– Leads to increases in fluid volume and Na levels– Decreases the reabsorption of K+– Maintains B/P and fluid balance

Regulation of Fluid Volume, cont

• Atrial natriuretic peptide or factor (ANP) (ANF)– Cardiac hormone– Released in response to increased pressure in the atria

(increased blood volume)– Opposes the renin-angiotensin-aldosterone system– Stimulates excretion of Na and H2O– Suppresses renin level– Decreases the release of aldosterone– Decreases ADH release– Reduces vascular resistance by causing vasodilatation

FLUID VOLUME DEFICITE

Hypovolemia: isotonic extracellular fluid deficit• Deficiency of both water & electrolytes• Caused by decreased intake, vomiting,

diarrhea, fluid shift

Dehydration: hypertonic extracellular fluid deficit

• Deficiency of water • Caused by water loss related to high blood

glucose, inadequate ADH production, high fever, excess sweating

FLUID VOLUME EXCESSExtracellular: isotonic fluid excess• Excess of both water and electrolytes• Caused by retention of water and electrolytes related to

kidney disease; overload with isotonic IV fluids

Intracellular: water excess• Excess of body water without excess electrolytes• Caused by over-hydration in the presence of renal failure;

administration of D5W

• WATER EXCESS : occurs rarely specially in those patients who are on Intravenous(IV) fluids and in some Psychiatric diseases.

• The excess of water decreases plasma

osmolality and causes over hydration.

HOMEOSTATIC CORECTION OF WATER EXCESS

ABNORMALITY OF ADH (DIABETES INSIPIDUS)

• Rare disease of posterior pituitary resulting in loss of ADH secretion.

• The loss of water increases plasma osmolality and causes dehydration of ICF.

• Body tries to respond with stimulation of thirst which increases the intake of water but due to disease of ADH there is no increase reabsorption of water from the kidneys so the balance is not restored and patient continues to excrete a large amount of urine although he is dehydrated

ABNORMALITY OF ADH (DIABETES INSIPIDUS)

Fluid shifting• 1st space shifting- normal distribution of fluid

in both the ECF compartment and ICF compartment.

• 2nd space shifting- excess accumulation of interstitial fluid (edema)

• 3rd space shifting- fluid accumulation in areas that are normally have no or little amounts of fluids (ascites)

Diagnostic Tests for water electrolyte balance

• Urine studies– Urine pH Urine specific gravity– Urine osmolarity– Urine creatinine clearance– Urine sodium– Urine potassium

Blood Studies• Serum Hematocrit = 40-54%/men, 38-47% for

women• Serum Creatinine = 0.6 – 1.5 mg/dl• BUN = 8-20 mg/dL• Serum osmolality• Serum Albumin – 3.5-5.5 g/dL• Serum Electrolytes

Diagnostic Tests for water electrolyte balance

Electrolytes• Anions : Negatively charged– Cl-

– HCO3-

– H2PO3-– H2PO4-

• Cations: positively charged– Na– K– Mg– Ca

COMPOSITION OF THE BODY FLUIDSEXTRA CELLULAR FLUIDS INTRACELLULAR FLUIDS

ANIONS CATIONS ANIONS CATIONS

Cl =100 mmol/LˉHCO3=26mmol/LORGANIC IONS =3 mmol/LPHOSPHATE = 1 mmol/LSULPHATE = 0.5 mmol/LPLASMA PROTEINS= 16 mmol/L

SODIUM = 140 mmol/LK+ = 4.5 mmol/LCa 2+ = 1.3 mmol/LMg 2+ = 0.7mmol/L

PHOSPHATE = 126HCO3 = 10 SULPHATE = 10ORGANIC IONS = 05PROTEINATE = 40As mmol / Kg of WATER

K+ = 165Mg+ = 14Na+ = 12Ca+ = very less

As mmol / Kg of WATER

Sodium

• Most abundant ECF cation (90%)• Determine the smolality of the blood• Na/K ATPase pump control active transport of

Na into out side the cell – 3 Na ions exchanged for 2 K ions

Na level regulation

• Intake & excretion of water• Renal regulation • 1. Intake of water in response to thirst as stimulated

or suppressed by plasma smolality• 2. Renal excretion of water in response ADH as

stimulated or inhibited by blood smolality• 3. Renal Na excretion as blood volume status– Aldosterone – Angiotensin 11 – ANP

Hypovolemic hyponatremia Renal loss (urine Na >20

mmol/day)

• Diuretics • Potassium depletion• Aldosterone deficiency• Salt loosing nephropathy

Extra renal loss or cellular shift (urine Na < 20 mmol/day)

• Vomiting• Diarrhea• Fluid loss with burn• Excess sweating• Excess loss with trauma• Potassium depletion

Thirst stimulated by hypovolemia and result in more hypotonic fluid

Normovolemic hyponatremia• Indicates problem with water balance 1. SIADH (Syndrome of inappropriate ADH regulation):

– Malignancies– Pulmonary disorders – CNS disorders) .

2. Pseudohyponatremia1. Sever hyperlipidemia

3. Sever hyperglycemia 4. Excess water intake (polydipsia or chronic thirst)5. Adrenal insufficiency

1. Decrease cortisol and aldosterone 2. decrease level of levels promote ADH secretion and water retention

(restore to normal volume )

Addison,s disesese• Primary adrenal insufficiency: – Addison’s disease: – Progressive destruction or dysfunction of

adrenal cortex– Most commonly is of an autoimmune

etiology, resulting from chronic destruction of the adrenal cortex

– All adrenal steroids are deficient

Symptoms of Addison’s disease• Fatique• Weakness• GI disturbance• Weight loss• Postprandial hypoglycemia• Dehydration• Hypotension• Hyponatremia• Hyperkalemia• Acidosis• Increased skin pigmentation can be seen with primary adrenal

insufficiency secondary to melanocyte stimulating activity associated with ACTH

Hypervolemic hyponatremia

Hypervolemic hy-ponatremia (urine Na

> 20 mmol/l

• Acute or chronic renal failure

Hypervolemic hy-ponatremia (urine Na

< 20 mmol/l

• Nephrotic syn-drome

• Hepatic cirrhosis• Congestive heart

failure

hypernatremiaExcess water loss ( hypotonic fluid loss)

Renal loss urine smolality is N/L (<300)

Extra renal loss( urine smolality is increased)

Diabetes insipidusTubular disorders (acute tubular necrossis)

Decrease water intake Increased Na intakeOr retension

Insensible loss (skin & breathing )Fever DiarrheaBurnsExposure to heat

Loss of thirst Hypertonic solutions of Na (Na bicarbonate)Hypertononc dialysis solutions-Problem in neonates-Hyperaldosteronism

Potassium

• Major intracellular cation• 20 time greate inside cells than out side cells• Many celular function requires low ECF K level• Only 2% of total K circulate in plasma•

Functions of K

• Regulation of – Neuromuscular excitability– Elevated K level decreases the resting membrane

potential (RMP) of the cell– Contraction of skeletal and heart muscles– ICF– Hydrogen ion concentration

Regulation of K level • Regulation by the kidney :– All K are reabsorbed in proximal tubules– In the distal tuble: additional K is secreted into urine in

Exchange of Na under the effect of ALDOSTERONE • Distribution of K between cells and ECF– Na/K ATPase pump: K loss if inhibited

• Hypoxia• Hypomagnesaemia• Digoxin overload

– Insulin : promote entry of K into cells by increasing Na/K ATPase activity

– Epinephrine : promote cellular uptake of K

hypokalemia

• GI loss– Vomiting– Diarrhea– Gastric suction– Intestinal

tumors– Malabsorption– Cancer therapy

• Renal loss– Diuretics – Nephritis– Renal tubular

acidosis– Hyperaldosteroni

sm– Cushing’s

syndrome– Hypomagnesaemi

a– Acute leukemia

• Cellular shift– Alkalosis– Insulin

overdose

Symptoms of hypokalemia

• < 3mmol/l– Weakness– Fatigue– Constipation– Can lead to paralysis– Increase risk of arrhythmias in pts with heart

disorders

hyperkalemia

• Decreased renal loss– Acute or

chronic RF– hypoaldosteron

ism– Addison’s

disease– diuretics

• Increased intake– Oral or IV K

therapy

• Artificial :• Sample

haemolysis• Thrombocytosis• Prolonged

torniquate• Drugs:

• Cellular shift– Acidosis– Muscle or

cellular injury– Chemotherap

y– Leukemia– Hemolysis– Diabetes

(insulin & hyperglycemia)

Symptoms of hyperkalemia

– Weakness– Tingling – Can lead to paralysis– Increase risk of arrhythmias and cardiac arrest in

pts with heart disorders

• Serum • Plasma

– Lithium– Advantageous for K when platelets counts are elevated

• Capillary blood• Heparinized venous or arterial blood

– With Direct ISE– Advantageous for K when platelets counts are elevated

• Urine:• No addition of preservatives

specimen for electrolytes measurement

Na+ and K+ measurement

• Specimens: serum, heparnized plasma, whole blood, sweet, urine, GIT fluids

• Methods:– AAS– FES– ISE– spectrophotometery

Flame Emission Spectrophotometry(Flame photometer)

• Sample is diluted with diluents containing known amount of lithium, as internal standard , and aspirated into propane –air flame.

• Na, K, and Li , when exited, emits light at 589 , 768 and 671nm , respectively

• The emitted lights are selected by interference filters and read by photodetectors

Flame Emission Spectrophotometry(Flame photometer)

• Na and K can be read at one time from diluted sample

• It is not common in laboratories:– Advances in electrochemistry of ISEs– Needs high amount of maintenance– Safety measures– Electrolyte exclusion effect

Spectrophotometric Methods

• Enzymatic methods:– activation of the enzyme beta -galactosidase by Na

to hydrolyze o-nitrophenyl-P-D-galactopyranoside (ONPG). The rate of production of o-nitrophenol (the chromophore) is measured at 420nm

• Chemical methods:– Nat or Kt binds to a macrocyclic chromophore and

produce spectral shift color that can be detected spectrophotometrically.

Spectrophotometric Methods

• Not common in laboratories:– High cost of reagents– Easy and availability of ISEs

Ion –Selective Electrode• Potentiometric electrode consisting of membrane

selectively permeable to single ion. The potential produced at membrane –sample interface is proportional to logarithm of the ionic activity or concentration.

• For Na : glass ISE are mostly used• For K : a valinomycin membrane is used to selectively

bind K,• 2 types of ISEs – Indirect– direct

Indirect ISE• Sample is diluted with large amount of

diluents before is introduced into the measurement champer.

• Advantage: minimize the effect of proteins in the electrodes

• Most common• Used in automated analyzers • Disadvantage : Electrolyte exclusion effect

Direct ISE• Sample is directly introduced into the measurement

champer without dilution.• Used on blood gas analyzer , POCT devices • Advantage : No electrolyte exclusion effect.• The measure electrolyte activity is directly proportion to

water phase of the plasma (not to the concentration in the total plasma volume)

• Results from direct ISE can be converted to total plasma volume by using FLAME MODE (mutiply by 0.93)

• Considered as method of choice:– Changes in lipid , proteins , other solids common in deferent

pathological conditions dose not affect results•

Problems with ISE

• Lack of analytical selectivity• Repeated protein coating of ISE membrane• Contamination of membranes with by ions

that

Electrolytes exclusion Effect• Exclusion of the electrolyte from the fraction of

total plasma volume that is occupied by the solids.– Proteins & Lipids ( 7% of plasma volume)– Electrolytes are measure in plasma water fraction

(93%).– Negative error in plasma electrolyte analysis

• Mainly problematic in some condition1. Pathological condition :

HyperlipidemiaHyperproteinemia (mutiple myeloma)

2. In methods that needs dilution FEA Indirect ISE

Chloride measurement

• Major extracelluat anion• Together with Na determine majority of

plasma osmolality.• Osmotic pressure• Maintenance of water balance• Anion – cation balance in ECF (electircal

neutrality)

Chloride measurement

• Hyperchloremia:– excess loss of HCO3

• GIT loss• RTA• Metabolic acidosis

• Hypochloremia:– excessive loss of Cl from prolonged vomiting– diabetic ketoacidosis– aldosterone deficiency– Saltlosing renal diseases such as pyelonephritis

• Specimens: serum, plasma , urine , sweet– Very stable in plasma or serum – No effect of hemolysis

• Analytical methods:– Coulometric –Amperometric titration– ISE– Reference range :– Serum or plasma: 98 to 107 mmol/l– Spinal fluid : 15% higher than plasma level

Chloride measurement

Measurement of sweet Cl-

• To confirm the diagnosis of cystic fibrosis• Most common genetic disorder in caucasians• Newborn screening program• Patients with CF have higher Na and Chloride– Cl- > 60mmol/l : CF presence– Cl- 40 to 60 mmol/ : borderline– Cl- < 40 : exclude CF

Plasma & urine osmolality

• Osmosis : the process that constitutes the movement of solvent across membrane in response to differences in osmotic pressure between two sides of the membrane.

• Osmometry: Techniques for the measurement of the solute particles that contributes to the osmotic pressure. ( Na , Cl, glucose , urea)

Calculation of plasma Osmolality

• mOs/kg = = 1.86 (Na[mmol/l]) + glucose[mmol/l] + urea[mmol/l) + 9• Or• mOs/kg = = 1.86 (Na[mmol/l]) + glucose[mg/dl]/18 + BUN [mg/dl)/2.8 + 9Reference Range: 275 to 300 mSm/kg

Measurement of smolality

• Freezing Point depression osmometer• Vapor pressure osmometer• Osmolal Gap : difference between measured

and calculated smolality– Presence of exogenous osmotic substances– Rule out suspected psedohyponatremia