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Fluid balance and electrolyte distribution in human body.

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<strong>Fluid</strong> <strong>balance</strong> <strong>and</strong> <strong>electrolyte</strong> <strong>distribution</strong><br />

<strong>in</strong> <strong>human</strong> <strong>body</strong>.<br />

Mass Percent<br />

• other way of describ<strong>in</strong>g the amount of solute <strong>in</strong> a solution<br />

• Describes what percentage of a solution by mass is<br />

comprised by solute.<br />

mass of solute<br />

mass of solute<br />

× 100 % =<br />

× 100%<br />

total mass of solution mass of solute + mass of solvent<br />

• Example<br />

A student prepares a solution from 5.00 g of sodium fluoride dissolved<br />

<strong>in</strong> 95.00 g of water.<br />

What is the mass percent of sodium fluoride


Us<strong>in</strong>g Moles to Describe the Amount of<br />

Substance <strong>in</strong> a Solution<br />

• A number of units may be used to describe the<br />

concentration of a solute <strong>in</strong> a solution.<br />

• The most common unit is molarity (M).<br />

• The Molarity of a solution is equal to the moles of solute<br />

divided by the total volume of the solution.<br />

M<br />

=<br />

moles solute<br />

L solution<br />

=<br />

molar<br />

mass<br />

mass<br />

( g)<br />

solute<br />

solute x L solution<br />

• If we know the mass of solute we dissolved <strong>in</strong> the<br />

solution, we can convert the mass the solute to moles of<br />

solute <strong>and</strong> calculate the molarity.<br />

• The Molality of a solution is equal to the moles of solute<br />

per kilogram of solvent<br />

Total <strong>body</strong> water <strong>and</strong><br />

its <strong>distribution</strong> <strong>in</strong> the <strong>body</strong><br />

compartments.<br />

The ma<strong>in</strong> functions of water <strong>in</strong><br />

the <strong>human</strong> organism.


Water<br />

Largest s<strong>in</strong>gle chemical component of the <strong>body</strong>:<br />

45-75% of <strong>body</strong> mass<br />

Fat (adipose tissue) is essentially water free, so<br />

there is relatively more or less water<br />

<strong>in</strong> the <strong>body</strong> depend<strong>in</strong>g on % fat composition<br />

Water is the solvent for most biological<br />

molecules with<strong>in</strong> the <strong>body</strong><br />

Water also participates <strong>in</strong> a variety of<br />

biochemical reactions, both anabolic <strong>and</strong><br />

catabolic<br />

Body fat measur<strong>in</strong>g<br />

Sk<strong>in</strong>fold Caliper<br />

http://www.l<strong>in</strong>ear-software.com/onl<strong>in</strong>e.html


<strong>Fluid</strong> Compartments<br />

Body <strong>Fluid</strong>s are separated by semi-permeable membranes <strong>in</strong>to various<br />

physiological (functional) compartments<br />

• Two Compartment Model<br />

- Intracellular = Cytoplasmic (<strong>in</strong>side cells)<br />

- Extracellular (outside cells)<br />

The Two Compartment Model is useful cl<strong>in</strong>ically for underst<strong>and</strong><strong>in</strong>g the<br />

<strong>distribution</strong> of many drugs <strong>in</strong> the <strong>body</strong><br />

• Three Compartment Model<br />

– [1] Intracellular = Cytoplasmic (<strong>in</strong>side cells)<br />

– Extracellular compartment is subdivided <strong>in</strong>to:<br />

• [2] Interstitial = Intercellular = Lymph (between the cells <strong>in</strong> the tissues)<br />

• [3] Plasma (fluid portion of the blood)<br />

The Three Compartment Model is more useful for underst<strong>and</strong><strong>in</strong>g<br />

physiological processes<br />

Other models with more compartments can sometimes be useful, e.g., consider lymph <strong>in</strong> the<br />

lymph vessels, CSF, ocular fluids, synovial <strong>and</strong> serous fluids as separate compartments<br />

<strong>Fluid</strong> Compartments<br />

• Total Body Water (TBW) - 42L,<br />

60% of <strong>body</strong> weight<br />

– Intracellular <strong>Fluid</strong> (ICF) -<br />

28L, 67% of TBW<br />

– Extracellular <strong>Fluid</strong> (ECF) -<br />

14L, 33% of TBW<br />

• Interstitial <strong>Fluid</strong> - 11L,<br />

80% ECF<br />

• Plasma - 3L, 20% of<br />

ECF


Water <strong>balance</strong><br />

– Sources for 2500 ml<br />

- average daily<br />

<strong>in</strong>take<br />

• Metabolic Water<br />

• Preformed Water<br />

– Ingested Foods<br />

– Ingested Liquids<br />

– Balance achieved if<br />

daily output also =<br />

2500 ml<br />

• GI tract<br />

• Lungs<br />

• Sk<strong>in</strong><br />

– evaporation<br />

– perspiration<br />

• Kidneys<br />

Water Movement Between the ICF <strong>and</strong> ECF<br />

Osmolality – the concentrations of solutes <strong>in</strong> water<br />

– solutes will <strong>in</strong>fluence the movement of water across membranes<br />

H 2<br />

O<br />

π = iRTc<br />

Aquapor<strong>in</strong>s- water channel prote<strong>in</strong>s <strong>in</strong> membranes<br />

Net filtration (Starl<strong>in</strong>g hypothesis)<br />

= forces favor<strong>in</strong>g filtration – forces oppos<strong>in</strong>g filtration<br />

As fluid flows through capillary it looses water <strong>and</strong> create greater osmotic<br />

return of water as it flows toward ve<strong>in</strong>ule end of capillary<br />

Forces favor<strong>in</strong>g filtration<br />

- Capillary hydrostatic pressure (blood pressure)<br />

- Interstitial oncotic pressure (water-pull<strong>in</strong>g)<br />

Forces favor<strong>in</strong>g reabsorption<br />

- Plasma oncotic pressure (water-pull<strong>in</strong>g)<br />

- Interstitial hydrostatic pressure<br />

H 2<br />

O<br />

filtration<br />

H 2<br />

O<br />

reabsorption


Oncotic pressure…Colloid osmotic pressure<br />

• is formed by colloid particles dissolved <strong>in</strong> solution<br />

• <strong>in</strong> plasma the major part forms prote<strong>in</strong>s 65-85 g/l<br />

Electrophoretic separation of plasma prote<strong>in</strong>s<br />

(directly proportional to size <strong>and</strong> charge)<br />

Album<strong>in</strong><br />

60%<br />

α 1<br />

globul<strong>in</strong> 1-antitryps<strong>in</strong>, 1-acid glycoprote<strong>in</strong><br />

α 2<br />

globul<strong>in</strong> haptoglob<strong>in</strong>, 2-macroglobul<strong>in</strong>,<br />

2-antiplasm<strong>in</strong>, ceruloplasm<strong>in</strong><br />

4% 7%<br />

β globul<strong>in</strong><br />

transfer<strong>in</strong>, complement, LDL<br />

10%<br />

fibr<strong>in</strong>ogen<br />

γ globul<strong>in</strong> = Imunoglobul<strong>in</strong>s<br />

IgA, IgD, IgE, IgG <strong>and</strong> IgM<br />

Mr 67x10 3 Mr150x10 3<br />

Mr340x10 3<br />

5% 14%<br />

Water Movement Between the ICF <strong>and</strong> ECF<br />

20L/day<br />

18L/day


Osmotic Equilibrium<br />

Plasma Osmolarity - Measures ECF Osmolarity<br />

• Plasma is cl<strong>in</strong>ically accessible<br />

• Dom<strong>in</strong>ated by [Na + ] <strong>and</strong> the associated anions<br />

• Under normal conditions, ECF osmolarity can be roughly estimated<br />

as:<br />

P OSM = 2 [Na + ] p<br />

……..270-300 mOsm<br />

{ P OSM = 2[Na + ] + 2[K + ] + [Urea] + [Glucose] }


Edema<br />

Accumulation of fluid with<strong>in</strong> the<br />

<strong>in</strong>terstitial spaces<br />

• Causes:<br />

– Increase <strong>in</strong> hydrostatic pressure (blood pressure / hypertension)<br />

– Losses or dim<strong>in</strong>ished production of plasma album<strong>in</strong> (hypoprote<strong>in</strong>emia<br />

…decrease <strong>in</strong> oncotic pressure /malnutrition (at <strong>in</strong>sufficient supply of prote<strong>in</strong>s<br />

…abdom<strong>in</strong>al edema/ <strong>in</strong>sufficient production of prote<strong>in</strong>s at cirrhosis/ large<br />

losses of prote<strong>in</strong>s by kidney at nephrotic syndrome/)<br />

- Increases <strong>in</strong> capillary permeability (at anaphylaxis, allergic<br />

reaction (release of histam<strong>in</strong>), <strong>in</strong>flammation)<br />

- Lymph obstruction – elephantitus, flibitus<br />

- Decreased resorption due to raised systemic venous<br />

pressure – edema due to heart failure<br />

Edema


Regulat<strong>in</strong>g <strong>Fluid</strong> Intake<br />

Thirst<br />

Thirst Quench<strong>in</strong>g<br />

1. 2.<br />

Wett<strong>in</strong>g the oral mucosa<br />

(temporary)<br />

Stretch<strong>in</strong>g of the stomach<br />

Decreased blood/<strong>body</strong><br />

fluid osmolarity =<br />

<strong>in</strong>creased hydration<br />

(dilution) of the blood is<br />

the most important<br />

Regulation of <strong>Fluid</strong> Output<br />

• Hormonal control<br />

– 1 Antidiuretic hormone (ADH) [neurohypophysis]<br />

– 2 Aldosterone [adrenal cortex]<br />

– 3 Atrial natriuretic peptide (ANP) [heart atrial walls]<br />

• Causes of physiologic fluid im<strong>balance</strong>s<br />

– Dehydration: ↓ blood pressure, ↓ GFR<br />

– Overhydration: ↑ blood pressure, ↑ GFR<br />

– Hyperventilation - water loss through lungs<br />

– Vomit<strong>in</strong>g & Diarrhea - excessive water loss<br />

– Fever - heavy perspiration<br />

– exudat<strong>in</strong>g Burns, contusion - fluid loss<br />

– Hemorrhage – if blood loss is severe


Atrial natriuretic peptide (ANP) is a 28-am<strong>in</strong>o acid peptide that is synthesized, stored, <strong>and</strong><br />

released by atrial myocytes <strong>in</strong> response to atrial distension<br />

- elevated levels of ANP are found dur<strong>in</strong>g hypervolemic states (elevated blood volume) <strong>and</strong><br />

congestive heart failure<br />

A second natriuretic peptide (bra<strong>in</strong>-type natriuretic peptide; BNP) is a 32-am<strong>in</strong>o acid peptide that<br />

is synthesized with<strong>in</strong> the ventricles (as well as <strong>in</strong> the bra<strong>in</strong> where it was first identified). Like<br />

ANP, BNP is released by the same mechanisms that release ANP, <strong>and</strong> it has similar<br />

physiological actions, BNP serves as sensitive, diagnostic markers for heart failure <strong>in</strong><br />

patients<br />

Regulation of <strong>Fluid</strong> Output


Osm V PB<br />

ADH<br />

Factors affect<strong>in</strong>g<br />

ADH release<br />

Ur<strong>in</strong>e osmolarity regulation by ADH<br />

ADH


Human angiotens<strong>in</strong>ogen<br />

is 118 am<strong>in</strong>o acids long<br />

Pathway of RAAS<br />

Pr<strong>in</strong>cipal cells & aldosterone


Atrial natriuretic peptide<br />

28-am<strong>in</strong>o acid peptide<br />

Distribution of Solutes<br />

Interstitial fluid is<br />

essentially an ultrafiltrate<br />

of plasma,<br />

water <strong>and</strong> <strong>electrolyte</strong>s move freely with<strong>in</strong><br />

this compartment <strong>and</strong> between it <strong>and</strong> the<br />

<strong>in</strong>travascular fluid.<br />

Intravascular fluid has almost the same<br />

composition as <strong>in</strong>terstitial fluid except<br />

for its higher prote<strong>in</strong> level.


Electrolyte Balance<br />

Electrolytes have 4 important physiological functions <strong>in</strong> the <strong>body</strong><br />

• essential m<strong>in</strong>erals <strong>in</strong> certa<strong>in</strong> biochemical reactions<br />

• control osmosis = control the movement of water between<br />

compartments<br />

• ma<strong>in</strong>ta<strong>in</strong> acid-base <strong>balance</strong><br />

• conduct electrical currents (depolarization events)<br />

Regulators:<br />

Aldosterone ↑ [Na + ] [Cl - ] [H 2 O] ↓ [K + ]<br />

Atrial Natriuretic Peptide (opposite effect)<br />

Antidiuretic Hormone ↑ [H 2 O] (↓ [solutes])<br />

Parathyroid Hormone ↑ [Ca ++ ] ↓ [HPO 4- ]<br />

Calciton<strong>in</strong> (opposite effect)<br />

Female sex hormones ↑ [H 2 O]<br />

Electrolytes<br />

• Sodium (Na + ) - 136-146 mmol/liter<br />

– Most abundant cation<br />

• major ECF cation (90% of cations present)<br />

• determ<strong>in</strong>es osmolarity of ECF<br />

– Regulation<br />

• Aldosterone<br />

• ADH<br />

• ANP<br />

– Homeostatic im<strong>balance</strong>s<br />

• Hyponatremia<br />

• Hypernatremia


Hypertonic Alterations - Related to sodium ga<strong>in</strong> or water loss<br />

• Hypernatremia<br />

– Serum sodium >146 mmol/L<br />

– Water movement from the ICF to the ECF<br />

• Intracellular dehydration<br />

– Manifestations:<br />

• Convulsions, pulmonary edema, tachycardia, etc.<br />

• Water deficit<br />

- Dehydration<br />

- Renal free water clearance<br />

- Manifestations:<br />

– Tachycardia, weak pulses<br />

– Elevated hematocrit <strong>and</strong> serum sodium level<br />

Hypotonic Alterations - Related to Hyponatremia or free water excess<br />

• Hyponatremia<br />

- Serum sodium level


Electrolytes<br />

• Chloride (Cl - ) - 95-103 mmol/L<br />

– Major ECF anion<br />

• helps <strong>balance</strong> osmotic potential <strong>and</strong> electrostatic equilibrium<br />

between fluid compartments<br />

• plasma membranes tend to be leaky to Cl - anions<br />

– Regulation: aldosterone<br />

– Homeostatic im<strong>balance</strong>s<br />

• Hypochloremia - results <strong>in</strong> muscle spasms, coma (usually<br />

occurs with hyponatremia) often due to prolonged vomit<strong>in</strong>g<br />

(elevated sweat chloride diagnostic of Cystic Fibrosis)<br />

Electrolytes<br />

• Potassium (K + )<br />

– Major ICF cation, concentration ma<strong>in</strong>ta<strong>in</strong>ed by the Na + /K + pump<br />

• <strong>in</strong>tracellular 120-125 mmol/L<br />

• plasma 3.5-5.0 mmol/L<br />

– Very important role <strong>in</strong> rest<strong>in</strong>g membrane potential (RMP) <strong>and</strong> <strong>in</strong><br />

action potentials = essential for transmission <strong>and</strong> conduction of nerve<br />

impulses, normal cardiac rhythms, <strong>and</strong> skeletal <strong>and</strong> smooth muscle<br />

contraction<br />

• Changes <strong>in</strong> pH affect K + <strong>balance</strong><br />

– Hydrogen ions accumulate <strong>in</strong> the ICF dur<strong>in</strong>g states of acidosis. K +<br />

shifts out to ma<strong>in</strong>ta<strong>in</strong> a <strong>balance</strong> of cations across the membrane.<br />

• Aldosterone, <strong>in</strong>sul<strong>in</strong>, <strong>and</strong> catecholam<strong>in</strong>es <strong>in</strong>fluence serum potassium<br />

levels<br />

• Homeostatic im<strong>balance</strong>s<br />

• Hypokalemia<br />

• Hyperkalemia


• Hypokalemia<br />

- Potassium level 5.5 mmol/L<br />

- Caused by <strong>in</strong>creased <strong>in</strong>take, shift of K+ from ICF, decreased renal excretion,<br />

<strong>in</strong>sul<strong>in</strong> deficiency, or cell trauma<br />

- Mild attacks<br />

- Hypopolarized membrane, caus<strong>in</strong>g neuromuscular irritability, T<strong>in</strong>gl<strong>in</strong>g of lips<br />

<strong>and</strong> f<strong>in</strong>gers, restlessness, <strong>in</strong>test<strong>in</strong>al cramp<strong>in</strong>g, <strong>and</strong> diarrhea<br />

- Severe attacks<br />

- The cell is not able to repolarize, result<strong>in</strong>g <strong>in</strong> muscle weakness, loss or<br />

muscle tone<br />

Electrolytes<br />

• Calcium (Ca 2+ )<br />

– Most abundant ion <strong>in</strong> <strong>body</strong><br />

• plasma 2.3-2.6 mmol/L<br />

• most stored <strong>in</strong> bone (98%) as hydroxyapatite<br />

- Necessary for structure of bones <strong>and</strong> teeth, blood clott<strong>in</strong>g, hormone<br />

secretion, <strong>and</strong> cell receptor function<br />

- Regulation:<br />

• Parathyroid Hormone (PTH) - ↑ blood Ca 2+<br />

• Calciton<strong>in</strong> (CT) - ↓ blood Ca 2+<br />

– Homeostatic im<strong>balance</strong>s:<br />

• Hypocalcemia - muscle cramps, convulsions<br />

• Hypercalcemia - vomit<strong>in</strong>g, cardiovascular symptoms, coma;<br />

prolonged abnormal calcium deposition, e.g., stone<br />

formation


Electrolytes<br />

• Phosphate (H 2 PO 4- , HPO 4<br />

2-<br />

, PO 4<br />

3-<br />

)<br />

– Important ICF anions; plasma 1.7-2.6 mmol/L<br />

• most (85%) is stored <strong>in</strong> bone as calcium salts<br />

• also comb<strong>in</strong>ed with lipids, prote<strong>in</strong>s, carbohydrates, nucleic acids (DNA<br />

<strong>and</strong> RNA), <strong>and</strong> high energy phosphate transport compound<br />

• important acid-base buffer <strong>in</strong> <strong>body</strong> fluids<br />

– Regulation - regulated <strong>in</strong> an <strong>in</strong>verse relationship with Ca 2+ by PTH <strong>and</strong><br />

calciton<strong>in</strong> <strong>and</strong> Vitam<strong>in</strong> D (If the concentration of one <strong>in</strong>creases, that of the other<br />

decreases)<br />

– Parathyroid hormone (PTH) - Increases plasma calcium levels<br />

– Vitam<strong>in</strong> D = Fat-soluble steroid - Increases calcium absorption from the GI tract<br />

– Calciton<strong>in</strong> - Decreases plasma calcium levels<br />

– Homeostatic im<strong>balance</strong>s<br />

• Phosphate concentrations shift oppositely from calcium concentrations<br />

<strong>and</strong> symptoms are usually due to the related calcium excess or deficit<br />

Hypophosphatemia <strong>and</strong> Hyperphosphatemia<br />

• Hypophosphatemia<br />

– Osteomalacia (soft bones)<br />

– Muscle weakness<br />

– Bleed<strong>in</strong>g disorders (platelet impairment)<br />

– Anemia<br />

– Leukocyte alterations<br />

• Hyperphosphatemia<br />

– High phosphate levels are related to the low calcium levels<br />

- Increased neuromuscular excitability (partial depolarization)<br />

- Muscle cramps


Electrolytes<br />

• Magnesium (Mg 2+ )<br />

– 2 nd most abundant <strong>in</strong>tracellular <strong>electrolyte</strong>, 0.8-1.3 mmol/L <strong>in</strong> plasma<br />

• more than half is stored <strong>in</strong> bone, most of the rest <strong>in</strong> ICF<br />

(cytoplasm)<br />

• important enzyme cofactor; <strong>in</strong>volved <strong>in</strong> neuromuscular activity,<br />

nerve transmission <strong>in</strong> CNS, <strong>and</strong> myocardial function<strong>in</strong>g<br />

– Homeostatic im<strong>balance</strong><br />

• Hypomagnesemia - Associated with hypocalcemia <strong>and</strong><br />

hypokalemia, Neuromuscular irritability,Tetany, Convulsions,<br />

Hyperactive reflexes vomit<strong>in</strong>g, cardiac arrhythmias<br />

• Hypermagnesemia - Muscle weakness, Hypotension,<br />

Respiratory depression, Lethargy, drows<strong>in</strong>ess, Bradycardia<br />

Acid-Base Balance<br />

• Normal metabolism produces H + (acidity)<br />

• Three Homeostatic mechanisms:<br />

– Buffer systems - <strong>in</strong>stantaneous; temporary<br />

– Exhalation of CO 2 - operates with<strong>in</strong> m<strong>in</strong>utes; cannot<br />

completely correct serious im<strong>balance</strong>s<br />

– Kidney excretion - can completely correct any im<strong>balance</strong><br />

(eventually)<br />

• Buffer Systems<br />

– Consists of a weak acid <strong>and</strong> the salt of that acid which<br />

functions as a weak base


Acid-Base Balance<br />

• Carbonic Acid - Bicarbonate Buffer<br />

– A weak base (carbonic anhydrase)<br />

H + + HCO 3- ⇔ H 2 CO 3 ⇔ H 2 O + CO 2<br />

• Phosphate Buffer<br />

NaOH + NaH 2 PO 4 ⇔ H 2 O + Na 2 HPO 4<br />

HCl + Na 2 HPO 4 ⇔ NaCl + NaH 2 PO 4<br />

• Prote<strong>in</strong> Buffer (resp. hemoglob<strong>in</strong> & album<strong>in</strong>)<br />

Most abundant buffer <strong>in</strong> <strong>body</strong> cells <strong>and</strong> plasma<br />

Am<strong>in</strong>o acids have am<strong>in</strong>e group (proton<br />

acceptor = weak base) <strong>and</strong> a carboxyl group<br />

(proton donor = weak acid)<br />

Acid-Base Balance<br />

• CNS <strong>and</strong> peripheral<br />

chemoreceptors control<br />

changes <strong>in</strong> blood pH<br />

• Increased [H + ] causes<br />

immediate hyperventilation<br />

<strong>and</strong> later <strong>in</strong>creased renal<br />

secretion of [H + ] <strong>and</strong> [NH 4+ ]<br />

• Decreased [H + ] causes<br />

immediate hypoventilation<br />

<strong>and</strong> later decreased renal<br />

secretion of [H + ] <strong>and</strong> [NH 4+ ]


• Acidosis<br />

– High blood [H + ]<br />

– Low blood pH, 7.45<br />

Acid-Base Im<strong>balance</strong>s<br />

• Acid-Base im<strong>balance</strong>s may be due to problems with ventilation or due to a<br />

variety of metabolic problems<br />

– Respiratory Acidosis (pCO 2<br />

> 45 mm Hg)<br />

– Respiratory Alkalosis (pCO 2<br />

< 35 mm Hg)<br />

– Metabolic Acidosis (HCO 3-<br />

< 23 mmol/l)<br />

– Metabolic Alkalosis (HCO 3-<br />

> 26 mmol/l)<br />

• Compensation: the physiological response to an acid-base im<strong>balance</strong><br />

beg<strong>in</strong>s with adjustments by the system less <strong>in</strong>volved<br />

Causes of Acid-Base Im<strong>balance</strong>s<br />

• Respiratory Acidosis<br />

– Chronic Obstructive Pulmonary Diseases e.g., emphysema,<br />

pulmonary fibrosis<br />

– Pneumonia<br />

• Respiratory Alkalosis<br />

– Hysteria<br />

– Fever<br />

– Asthma


Causes of Acid-Base Im<strong>balance</strong>s<br />

• Metabolic Acidosis<br />

– Diabetic ketoacidosis, Lactic acidosis<br />

– Salicylate poison<strong>in</strong>g (children)<br />

– Methanol, ethylene glycol poison<strong>in</strong>g<br />

– Renal failure<br />

– Diarrhea<br />

• Metabolic Alkalosis<br />

– Prolonged vomit<strong>in</strong>g<br />

– Diuretic therapy<br />

– Hyperadrenocortical disease<br />

– Exogenous base (antacids, bicarbonate IV, citrate toxicity after<br />

massive blood transfusions)<br />

Metabolic Acidosis


Metabolic Alkalosis<br />

Respiratory Acidosis


Respiratory Alkalosis<br />

Electrolyte Balance<br />

Electrolytes have 4 important physiological functions <strong>in</strong> the <strong>body</strong><br />

• essential m<strong>in</strong>erals <strong>in</strong> certa<strong>in</strong> biochemical reactions<br />

• control osmosis = control the movement of water between<br />

compartments<br />

• ma<strong>in</strong>ta<strong>in</strong> acid-base <strong>balance</strong><br />

• conduct electrical currents (depolarization events)<br />

Regulators:<br />

Aldosterone ↑ [Na + ] [Cl - ] [H 2 O] ↓ [K + ]<br />

Atrial Natriuretic Peptide (opposite effect)<br />

Antidiuretic Hormone ↑ [H 2 O] (↓ [solutes])<br />

Parathyroid Hormone ↑ [Ca ++ ] ↓ [HPO 4- ]<br />

Calciton<strong>in</strong> (opposite effect)<br />

Female sex hormones ↑ [H 2 O]


Electrolytes<br />

• Sodium (Na + ) - 136-146 mmol/liter<br />

– Most abundant cation<br />

• major ECF cation (90% of cations present)<br />

• determ<strong>in</strong>es osmolarity of ECF<br />

Plasma OSM = 2[Na + ] + 2[K + ] + [Urea] + [Glucose]<br />

– Regulation<br />

• Aldosterone<br />

• ADH<br />

• ANP<br />

– Homeostatic im<strong>balance</strong>s<br />

• Hyponatremia<br />

• Hypernatremia<br />

Hypertonic Alterations - Related to sodium ga<strong>in</strong> or water loss<br />

• Hypernatremia<br />

– Serum sodium >146 mmol/L<br />

– Intake of hypertonic salt solution<br />

– Water movement from the ICF to the ECF<br />

• Intracellular dehydration<br />

– Manifestations: <strong>in</strong> consequence of cell dehydration<br />

• Excitability, convulsions, or on the other h<strong>and</strong> drows<strong>in</strong>ess<br />

accompany<strong>in</strong>g with pulmonary edema, tachycardia, etc.<br />

• Water deficit<br />

- Dehydration (osmotic diuresis at glycosuria (diabetes),<br />

gastro<strong>in</strong>test<strong>in</strong>al losses-osmotic diarrhea, <strong>in</strong>fectious enteritis, high<br />

fever, burn <strong>in</strong>jury, elevated perspiration)<br />

- Renal free water clearance<br />

- Manifestations:<br />

– Tachycardia, weak pulses<br />

– Elevated hematocrit <strong>and</strong> serum sodium level


Hypernatremia<br />

Serum sodium >160 mmol/L <strong>in</strong> 60 % lethal<br />

Therapy:<br />

at water deficit – isotonic solutions (physiological sal<strong>in</strong>e<br />

solution) or slightly hypotonic (2/3 F)<br />

at normovolemia or hypervolemia – thiazide diuretics<br />

(hydrochlorothiazide, decreas<strong>in</strong>g of <strong>electrolyte</strong>s reabsorption <strong>in</strong><br />

renal tubules) <strong>and</strong> 5% glucose<br />

frequent monitor<strong>in</strong>g of <strong>electrolyte</strong> plasma level dur<strong>in</strong>g the<br />

treatment, avoid to fast reestablishment of the <strong>electrolyte</strong> level<br />

(max 1-2 mmol/L/h <strong>and</strong> 12 mmol/L/day<br />

Hypotonic Alterations - Related to Hyponatremia or free water excess<br />

• Hyponatremia<br />

- Serum sodium level


Hyponatremia<br />

!<br />

- water moves <strong>in</strong>to cells based on osmolarity difference, bra<strong>in</strong> cells (neurons)<br />

decrease water uptake by compensatory mechanisms decreas<strong>in</strong>g the <strong>in</strong>tracellular<br />

osmolarity by elevation of K + efflux (dur<strong>in</strong>g 24h), <strong>and</strong> organic substances metabolism<br />

(dur<strong>in</strong>g 48h, e.g. elim<strong>in</strong>ation of polyalcohols, am<strong>in</strong>oacids, chol<strong>in</strong> derivates)<br />

!<br />

Therapy:<br />

the major risk is to fast reestablish the normal level of Na + ions. The lower<br />

osmolarity of neurons due to compensatory mechanisms causes water efflux from<br />

the neurons, the neurons will shr<strong>in</strong>k <strong>and</strong> released from myel<strong>in</strong> sheath!!!<br />

1. if the disnatremia was developed dur<strong>in</strong>g the last 48hrs, than fast correction<br />

could be made (1-2mmol/L/h)<br />

2. if plasma [Na + ] is 105-120 mmol/L <strong>and</strong> neurological symptoms are present make<br />

the correction by 1-2mmol/L/h<br />

without neurological symptoms the speed of correction could be only<br />

0.5mmol/L/h<br />

3. if plasma [Na + ] is less than 105 mmol/L, first 20 mmol/L at 1-2mmol/L/h, <strong>and</strong> then<br />

slowly<br />

Hyponatremia<br />

Calculation of total need of Na +<br />

mmol Na + = mass (kg) x f x (targeted Na + - determ<strong>in</strong>ed Na + )<br />

f = 0.6 for man<br />

f = 0.55 for woman<br />

Example: 70 kg weighted man has plasma [Na + ] 115 mmol/L, we would like to<br />

<strong>in</strong>crease the [Na + ] to 127 mmol/L/day (i.e. by 12 mmol/L)<br />

mmol Na + = 70 x 0.6 x (12) = 504<br />

concentrations of available salt solutions:<br />

0.9% NaCl (physiological sal<strong>in</strong>e solution)…1ml = 0.15 mmol Na + <strong>and</strong> Cl -<br />

10% NaCl ….1ml = 1.7 mmol Na + <strong>and</strong> Cl -<br />

5.8% NaCl …1ml = 1 mmol Na + <strong>and</strong> Cl -<br />

4.2% NaHCO 3<br />

….1ml = 0.5 mmol Na + <strong>and</strong> HCO 3<br />

-


• Chloride (Cl - ) - 95-108 mmol/L<br />

– Major ECF anion<br />

• helps <strong>balance</strong> osmotic potential <strong>and</strong> electrostatic equilibrium<br />

between fluid compartments<br />

• plasma membranes tend to be leaky to Cl - anions<br />

– Regulation: aldosterone<br />

– Homeostatic im<strong>balance</strong>s<br />

• Hypochloremia - results <strong>in</strong> muscle spasms, coma (usually<br />

occurs with hyponatremia) often due to prolonged vomit<strong>in</strong>g<br />

(elevated sweat chloride diagnostic of Cystic Fibrosis)<br />

Hypochloremia with normonatremia results <strong>in</strong> metabolic<br />

hypochloremic alkalosis<br />

Heperchloremia with normonatremia results <strong>in</strong> metabolic<br />

hyperchloremic acidosis<br />

Comb<strong>in</strong>ed dis<strong>balance</strong>s are treated based on the plasma [Na + ]<br />

Hypochloremia with normonatremia or hypernatremia (e.g. due to<br />

adm<strong>in</strong>istration of drugs with Na + , such as NaHCO 3<br />

, Na-lactate, Na-acetate,<br />

..), vomit<strong>in</strong>g at hyperaldosteronism (e.g. at activation of JG cells due to<br />

stenosis of renal artery)<br />

1. treatment of the cause, e.g. antiemetics at vomit<strong>in</strong>g<br />

2. solution NaCl, KCl at hypokalemia, 4.2% Arg<strong>in</strong><strong>in</strong>hydrochloride at significant<br />

alkalosis<br />

Calculation of total need of Cl -<br />

mmol Cl - = mass (kg) x 0.3 x BE<br />

where BE is base excess…. is <strong>in</strong> the normal range from -2.5 to +2.5 mmol/L, is equal to<br />

amount of strong acid (or base) which is needed to titrate 1L of plasma to pH 7.4 at normal<br />

pCO 2 (5.3 kPa <strong>and</strong> temp. 37 °C)<br />

<strong>in</strong> the case, where respiratory compensatory mechanism is <strong>in</strong>volved <strong>in</strong> regulation of pH (at<br />

the alkalosis is pCO 2 due to hypoventilation), then use Nejedly’s formula:<br />

mmol Cl - = mass (kg) x 0.3 x BE x<br />

pH determ<strong>in</strong>ed<br />

-pH targeted<br />

pH determ<strong>in</strong>ed<br />

-pH X<br />

7.248<br />

pCO 2<br />

2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5<br />

pH X<br />

7.67 7.61 7.567 7.517 7.487 7.457 7.427 7.397 7.377 7.35 7.332 7.314 7.298 7.28 7.263


Hyperchloremia with normonatreia<br />

1. treatment of the cause, obstruction of ur<strong>in</strong>ary tract (accompanied with<br />

hypernatremia <strong>and</strong> hyperkalemia), hypoaldosteronism, drug<br />

adm<strong>in</strong>istration e.g. HCl, NH4Cl, lys<strong>in</strong>e-HCl, arg<strong>in</strong><strong>in</strong>e-HCl), acute<br />

diarrhea (accompanied with hypokalemia)<br />

2. treatment of acidosis by NaHCO 3<br />

if pH of artery blood is


• Hypokalemia<br />

- Potassium level


Calcium (Ca 2+ )<br />

– Most abundant ion <strong>in</strong> <strong>body</strong><br />

• plasma 2.3-2.6 mmol/L<br />

• most stored <strong>in</strong> bone (98%) as hydroxyapatite<br />

- Necessary for structure of bones <strong>and</strong> teeth, blood clott<strong>in</strong>g, hormone<br />

secretion, <strong>and</strong> cell receptor function<br />

- Regulation:<br />

• Parathyroid Hormone (PTH) - ↑ blood Ca 2+<br />

• Calciton<strong>in</strong> (CT) - ↓ blood Ca 2+<br />

- Homeostatic im<strong>balance</strong>s:<br />

Hypocalcemia (necrotic pancreatitis, malabsorption, hypoparathyreosis,<br />

vitam<strong>in</strong> D deficit (osteomalacia)) - muscle cramps, convulsions<br />

Therapy: 1. cause, 2. 10% Ca-gluconicum (10ml ampules, 1ml =<br />

0.25mmol)<br />

Hypercalcemia (hyperparathyreosis, hypervitam<strong>in</strong>osis D, osteolytic tumor<br />

metastasis)- vomit<strong>in</strong>g, cardiovascular symptoms, coma (critical [Ca+] is<br />

above 3.75 mmol/l); prolonged abnormal calcium deposition, e.g.,<br />

stone formation<br />

Therapy: 1.cause, 2. <strong>in</strong>crease of diuresis by furosemide (at 3L/day),<br />

glucocorticoids decreas<strong>in</strong>g Ca+ absorption by <strong>in</strong>test<strong>in</strong>e, calciton<strong>in</strong><br />

Phosphate (H 2 PO 4- , HPO 4<br />

2-<br />

, PO 4<br />

3-<br />

)<br />

– Important ICF anions; plasma 0.7-1.5 mmol/L<br />

• most (85%) is stored <strong>in</strong> bone as calcium salts<br />

• also comb<strong>in</strong>ed with lipids, prote<strong>in</strong>s, carbohydrates, nucleic acids<br />

(DNA <strong>and</strong> RNA), <strong>and</strong> high energy phosphate transport compound<br />

• important acid-base buffer <strong>in</strong> <strong>body</strong> fluids<br />

– Regulation - regulated <strong>in</strong> an <strong>in</strong>verse relationship with Ca 2+ by PTH <strong>and</strong><br />

calciton<strong>in</strong> <strong>and</strong> Vitam<strong>in</strong> D (If the concentration of one <strong>in</strong>creases, that of<br />

the other decreases)<br />

– Parathyroid hormone (PTH) - Increases plasma calcium levels<br />

– Vitam<strong>in</strong> D (fat-soluble steroid) - Increases calcium absorption from the<br />

GI tract<br />

– Calciton<strong>in</strong> - Decreases plasma calcium levels<br />

– Homeostatic im<strong>balance</strong>s<br />

• Phosphate concentrations shift oppositely from calcium<br />

concentrations <strong>and</strong> symptoms are usually due to the related<br />

calcium excess or deficit


Hypophosphatemia <strong>and</strong> Hyperphosphatemia<br />

• Hypophosphatemia<br />

(abrosia, malnutrition, renal losses, hyperparathyreosis)<br />

– Osteomalacia (soft bones)<br />

– Muscle weakness<br />

– Bleed<strong>in</strong>g disorders (platelet impairment)<br />

– Anemia<br />

– Leukocyte alterations<br />

Therapy: significant decrease


Acid-Base Balance<br />

• Normal metabolism produces H + (acidity)<br />

• Three Homeostatic mechanisms:<br />

– Buffer systems - <strong>in</strong>stantaneous; temporary<br />

– Exhalation of CO 2 - operates with<strong>in</strong> m<strong>in</strong>utes; cannot<br />

completely correct serious im<strong>balance</strong>s<br />

– Kidney excretion - can completely correct any im<strong>balance</strong><br />

(eventually)<br />

• Buffer Systems<br />

– Consists of a weak acid <strong>and</strong> the salt of that acid which<br />

functions as a weak base<br />

Acid-Base Balance<br />

• Carbonic Acid - Bicarbonate Buffer<br />

– A weak base (carbonic anhydrase)<br />

H + + HCO 3- ⇔ H 2 CO 3 ⇔ H 2 O + CO 2<br />

• Phosphate Buffer<br />

NaOH + NaH 2 PO 4 ⇔ H 2 O + Na 2 HPO 4<br />

HCl + Na 2 HPO 4 ⇔ NaCl + NaH 2 PO 4<br />

- ma<strong>in</strong>ly <strong>in</strong>tracellularly, dur<strong>in</strong>g acidemia proton is bound, dur<strong>in</strong>g alkalemia proton is<br />

released via cell membrane K + /H + antiporter<br />

• Prote<strong>in</strong> Buffer (resp. album<strong>in</strong> & hemoglob<strong>in</strong> )<br />

Am<strong>in</strong>o acids have am<strong>in</strong>e group (proton<br />

acceptor = weak base) <strong>and</strong> a carboxyl group<br />

(proton donor = weak acid)<br />

hemoglob<strong>in</strong>- oxyhemoglob<strong>in</strong> systém, where<br />

oxyhemoglob<strong>in</strong> is stronger acid than<br />

hemoglob<strong>in</strong> (proton is more simply released)


Acid-Base <strong>balance</strong> systems <strong>in</strong> blood<br />

1. Carbonic Acid - Bicarbonate Buffer 53 %<br />

2. Hemoglob<strong>in</strong>-oxyhemoglob<strong>in</strong> 35 %<br />

3. Plasma prote<strong>in</strong>s 7 %<br />

4. Phosphate buffers 5 %<br />

plasma pH 7.37-7.43<br />

Examples:<br />

Prescribe <strong>in</strong>fusion therapy for m<strong>in</strong>eral blood alteration:<br />

a) 70 kg man with polyuria 3.5 L/d, plasma [K + ] = 2.8 mmol/L, ur<strong>in</strong>e<br />

[K + ] = 13 mmol/L <strong>and</strong> with normal levels of other m<strong>in</strong>erals <strong>and</strong><br />

normal blood pH<br />

b) 60 kg woman with plasma [Cl - ] = 78 mmol/L with normal levels of<br />

other m<strong>in</strong>erals <strong>and</strong> blood pH 7.52, pCO 2 6.5 kPa, BE +4.2 <strong>and</strong><br />

normal renal function

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