Fluid balance and electrolyte distribution

in human body.

Mass Percent

• other way of describing the amount of solute in a solution• Describes what percentage of a solution by mass is

comprised by solute.

• ExampleA student prepares a solution from 5.00 g of sodium fluoride dissolved in 95.00 g of water.What is the mass percent of sodium fluoride?

%100%100 ×+

=×solventofmasssoluteofmass

soluteofmasssolutionofmasstotal

soluteofmass

Using Moles to Describe the Amount of Substance in a Solution

• A number of units may be used to describe the concentration of a solute in a solution.

• The most common unit is molarity (M).• The Molarity of a solution is equal to the moles of solute

divided by the total volume of the solution.

• If we know the mass of solute we dissolved in the solution, we can convert the mass the solute to moles of solute and calculate the molarity.

• The Molality of a solution is equal to the moles of solute per kilogram of solvent

solutionLxsolutemassmolarsolutegmass

solutionLsolutemoles

M)(==

Total body water and

its distribution in the body

compartments.

The main functions of water in

the human organism.

Water

Water is the solvent for most biological

molecules within the body

Largest single chemical component of the body: 45-75% of body mass

Water also participates in a variety of

biochemical reactions, both anabolic and

catabolic

Fat (adipose tissue) is essentially water free, so

there is relatively more or less waterin the body depending on % fat composition

Body fat measuring

http://www.linear-software.com/online.html

Skinfold Caliper

Fluid CompartmentsBody Fluids are separated by semi-permeable membranes into various

physiological (functional) compartments

• Two Compartment Model- Intracellular = Cytoplasmic (inside cells)- Extracellular (outside cells)

The Two Compartment Model is useful clinically for understanding the distribution of many drugs in the body

• Three Compartment Model– [1] Intracellular = Cytoplasmic (inside cells)– Extracellular compartment is subdivided into:

• [2] Interstitial = Intercellular = Lymph (between the cells in the tissues)• [3] Plasma (fluid portion of the blood)

The Three Compartment Model is more useful for understanding physiological processes

Other models with more compartments can sometimes be useful, e.g., consider lymph in the lymph vessels, CSF, ocular fluids, synovial and serous fluids as separate compartments

Fluid Compartments

• Total Body Water (TBW) - 42L, 60% of body weight– Intracellular Fluid (ICF) -

28L, 67% of TBW– Extracellular Fluid (ECF) -

14L, 33% of TBW• Interstitial Fluid - 11L,

80% ECF• Plasma - 3L, 20% of

ECF

Water balance

– Sources for 2500 ml - average daily intake

• Metabolic Water• Preformed Water

– Ingested Foods– Ingested Liquids

– Balance achieved if daily output also = 2500 ml

• GI tract• Lungs • Skin

– evaporation – perspiration

• Kidneys

Water Movement Between the ICF and ECF

Osmolality – the concentrations of solutes in water– solutes will influence the movement of water across membranes

Forces favoring filtration- Capillary hydrostatic pressure (blood pressure)- Interstitial oncotic pressure (water-pulling)

Forces favoring reabsorption- Plasma oncotic pressure (water-pulling)- Interstitial hydrostatic pressure

Aquaporins- water channel proteins in membranes

Net filtration (Starling hypothesis)

= forces favoring filtration – forces opposing filtration

As fluid flows through capillary it looses water and create greater osmotic

return of water as it flows toward veinule end of capillary

H2O

ππππ = iRTc

H2O

filtration

reabsorption

H2O

Oncotic pressure…Colloid osmotic pressure

• is formed by colloid particles dissolved in solution• in plasma the major part forms proteins 65-85 g/l

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Water Movement Between the ICF and ECF

20L/day 18L/day

Osmotic Equilibrium

Plasma Osmolarity - Measures ECF Osmolarity

• Plasma is clinically accessible• Dominated by [Na+] and the associated anions• Under normal conditions, ECF osmolarity can be roughly estimated

as:

POSM = 2 [Na+]p ……..270-300 mOsm

{ POSM = 2[Na+] + 2[K+] + [Urea] + [Glucose] }

Edema

• Causes:– Increase in hydrostatic pressure (blood pressure / hypertension)– Losses or diminished production of plasma albumin (hypoproteinemia

…decrease in oncotic pressure /malnutrition (at insufficient supply of proteins …abdominal edema/ insufficient production of proteins at cirrhosis/ large

Accumulation of fluid within the interstitial spaces

losses of proteins by kidney at nephrotic syndrome/)- Increases in capillary permeability (at anaphylaxis, allergic reaction (release of histamin), inflammation)- Lymph obstruction – elephantitus, flibitus- Decreased resorption due to raised systemic venous pressure – edema due to heart failure

Edema

Thirst Thirst Quenching

Regulating Fluid Intake

Wetting the oral mucosa (temporary)

Stretching of the stomach

Decreased blood/body fluid osmolarity = increased hydration (dilution) of the blood is the most important

1. 2.

Regulation of Fluid Output

• Hormonal control

– 1 Antidiuretic hormone (ADH) [neurohypophysis]

– 2 Aldosterone [adrenal cortex]

– 3 Atrial natriuretic peptide (ANP) [heart atrial walls]

• Causes of physiologic fluid imbalances

– Dehydration: ↓ blood pressure, ↓ GFR

– Overhydration: ↑ blood pressure, ↑ GFR

– Hyperventilation - water loss through lungs

– Vomiting & Diarrhea - excessive water loss

– Fever - heavy perspiration

– exudating Burns, contusion - fluid loss

– Hemorrhage – if blood loss is severe

Atrial natriuretic peptide (ANP) is a 28-amino acid peptide that is synthesized, stored, and

released by atrial myocytes in response to atrial distension

- elevated levels of ANP are found during hypervolemic states (elevated blood volume) and

congestive heart failure

A second natriuretic peptide (brain-type natriuretic peptide; BNP) is a 32-amino acid peptide that

is synthesized within the ventricles (as well as in the brain where it was first identified). Like

ANP, BNP is released by the same mechanisms that release ANP, and it has similar

physiological actions, BNP serves as sensitive, diagnostic markers for heart failure in

patients

Regulation of Fluid Output

ADH releaseFactors affecting

Osm V PB

ADH

Urine osmolarity regulation by ADH

ADH

Pathway of RAAS

Human angiotensinogenis 118 amino acids long

Principal cells & aldosterone

Atrial natriuretic peptide

28-amino acid peptide

Distribution of Solutes

Interstitial fluid is essentially an ultrafiltrateof plasma,

Intravascular fluid has almost the same composition as interstitial fluid except for its higher protein level.

water and electrolytes move freely within this compartment and between it and the intravascular fluid.

Electrolyte Balance

Electrolytes have 4 important physiological functions in the body• essential minerals in certain biochemical reactions• control osmosis = control the movement of water between

compartments• maintain acid-base balance• conduct electrical currents (depolarization events)

Regulators:Aldosterone ↑↑↑↑ [Na+] [Cl-] [H2O] ↓↓↓↓ [K+]Atrial Natriuretic Peptide (opposite effect)Antidiuretic Hormone ↑↑↑↑ [H2O] (↓↓↓↓ [solutes])Parathyroid Hormone ↑↑↑↑ [Ca++] ↓↓↓↓ [HPO4

-]Calcitonin (opposite effect)Female sex hormones ↑↑↑↑ [H2O]

Electrolytes

• Sodium (Na+) - 136-146 mmol/liter– Most abundant cation

• major ECF cation (90% of cations present)• determines osmolarity of ECF

– Regulation• Aldosterone• ADH• ANP

– Homeostatic imbalances• Hyponatremia• Hypernatremia

Hypertonic Alterations - Related to sodium gain or water loss

• Hypernatremia– Serum sodium >146 mmol/L– Water movement from the ICF to the ECF

• Intracellular dehydration– Manifestations:

• Convulsions, pulmonary edema, tachycardia, etc.

• Water deficit- Dehydration- Renal free water clearance- Manifestations:– Tachycardia, weak pulses– Elevated hematocrit and serum sodium level

Hypotonic Alterations - Related to Hyponatremia or free water excess

• Hyponatremia- Serum sodium level <135 mmol/L- decreases the ECF osmotic pressure, and water moves into the cell - Manifestations:

- muscle weakness, coma

• Water Excess- Compulsive water drinking- Syndrome of inappropriate ADH (SIADH)- Manifestations:

- cerebral edema, muscle twitching, headache, and weight gain

Electrolytes

• Chloride (Cl-) - 95-103 mmol/L– Major ECF anion

• helps balance osmotic potential and electrostatic equilibrium between fluid compartments

• plasma membranes tend to be leaky to Cl- anions– Regulation: aldosterone– Homeostatic imbalances

• Hypochloremia - results in muscle spasms, coma (usually occurs with hyponatremia) often due to prolonged vomiting(elevated sweat chloride diagnostic of Cystic Fibrosis)

Electrolytes

• Potassium (K+)– Major ICF cation, concentration maintained by the Na+/K+ pump

• intracellular 120-125 mmol/L• plasma 3.5-5.0 mmol/L

– Very important role in resting membrane potential (RMP) and in action potentials = essential for transmission and conduction of nerve impulses, normal cardiac rhythms, and skeletal and smooth muscle contraction

• Changes in pH affect K+ balance– Hydrogen ions accumulate in the ICF during states of acidosis. K+

shifts out to maintain a balance of cations across the membrane.

• Aldosterone, insulin, and catecholamines influence serum potassium levels

• Homeostatic imbalances• Hypokalemia• Hyperkalemia

• Hypokalemia- Potassium level <3.5 mmol/L- Causes can be reduced intake of potassium, increased entry of potassium, and increased loss of potassium- Manifestations:

Membrane hyperpolarization causes a decrease in neuromuscular excitability, skeletal muscle weakness, smooth muscle atony, and cardiac dysrhythmias

• Hyperkalemia- Potassium level >5.5 mmol/L- Caused by increased intake, shift of K+ from ICF, decreased renal excretion,

insulin deficiency, or cell trauma- Mild attacks

- Hypopolarized membrane, causing neuromuscular irritability, Tingling of lips and fingers, restlessness, intestinal cramping, and diarrhea

- Severe attacks- The cell is not able to repolarize, resulting in muscle weakness, loss or

muscle tone

Electrolytes

• Calcium (Ca2+)– Most abundant ion in body

• plasma 2.3-2.6 mmol/L• most stored in bone (98%) as hydroxyapatite

- Necessary for structure of bones and teeth, blood clotting, hormone secretion, and cell receptor function

- Regulation:• Parathyroid Hormone (PTH) - ↑ blood Ca2+

• Calcitonin (CT) - ↓ blood Ca2+

– Homeostatic imbalances:• Hypocalcemia - muscle cramps, convulsions• Hypercalcemia - vomiting, cardiovascular symptoms, coma;

prolonged � abnormal calcium deposition, e.g., stone formation

Electrolytes

• Phosphate (H2PO4-, HPO4

2-, PO43-)

– Important ICF anions; plasma 1.7-2.6 mmol/L• most (85%) is stored in bone as calcium salts• also combined with lipids, proteins, carbohydrates, nucleic acids (DNA

and RNA), and high energy phosphate transport compound• important acid-base buffer in body fluids

– Regulation - regulated in an inverse relationship with Ca2+ by PTH and calcitonin and Vitamin D (If the concentration of one increases, that of the other decreases)

– Parathyroid hormone (PTH) - Increases plasma calcium levels– Vitamin D = Fat-soluble steroid - Increases calcium absorption from the GI tract– Calcitonin - Decreases plasma calcium levels

– Homeostatic imbalances• Phosphate concentrations shift oppositely from calcium concentrations

and symptoms are usually due to the related calcium excess or deficit

Hypophosphatemia and Hyperphosphatemia

• Hypophosphatemia– Osteomalacia (soft bones)– Muscle weakness– Bleeding disorders (platelet impairment)– Anemia– Leukocyte alterations

• Hyperphosphatemia– High phosphate levels are related to the low calcium levels- Increased neuromuscular excitability (partial depolarization)- Muscle cramps

Electrolytes

• Magnesium (Mg2+)– 2nd most abundant intracellular electrolyte, 0.8-1.3 mmol/L in plasma

• more than half is stored in bone, most of the rest in ICF (cytoplasm)

• important enzyme cofactor; involved in neuromuscular activity, nerve transmission in CNS, and myocardial functioning

– Homeostatic imbalance• Hypomagnesemia - Associated with hypocalcemia and

hypokalemia, Neuromuscular irritability,Tetany, Convulsions, Hyperactive reflexes vomiting, cardiac arrhythmias

• Hypermagnesemia - Muscle weakness, Hypotension, Respiratory depression, Lethargy, drowsiness, Bradycardia

Acid-Base Balance

• Normal metabolism produces H+ (acidity)

• Three Homeostatic mechanisms: – Buffer systems - instantaneous; temporary– Exhalation of CO2 - operates within minutes; cannot

completely correct serious imbalances– Kidney excretion - can completely correct any imbalance

(eventually)

• Buffer Systems– Consists of a weak acid and the salt of that acid which

functions as a weak base

Acid-Base Balance

• Carbonic Acid - Bicarbonate Buffer– A weak base (carbonic anhydrase)

H+ + HCO3- ⇔⇔⇔⇔ H2CO3 ⇔⇔⇔⇔ H2O + CO2

• Phosphate BufferNaOH + NaH2PO4 ⇔⇔⇔⇔ H2O + Na2HPO4

HCl + Na2HPO4 ⇔⇔⇔⇔ NaCl + NaH2PO4

• Protein Buffer (resp. hemoglobin & albumin)

Most abundant buffer in body cells and plasma

Amino acids have amine group (proton

acceptor = weak base) and a carboxyl group

(proton donor = weak acid)

Acid-Base Balance

• CNS and peripheral chemoreceptors controlchanges in blood pH

• Increased [H+] causes immediate hyperventilation and later increased renal secretion of [H+] and [NH4

+]

• Decreased [H+] causes immediate hypoventilation and later decreased renal secretion of [H+] and [NH4

+]

Acid-Base Imbalances

• Acidosis– High blood [H+]– Low blood pH, <7.35Alkalosis– Low blood [H+]– High blood pH, >7.45

• Acid-Base imbalances may be due to problems with ventilation or due to a variety of metabolic problems– Respiratory Acidosis (pCO2 > 45 mm Hg)– Respiratory Alkalosis (pCO2 < 35 mm Hg)– Metabolic Acidosis (HCO3

- < 23 mmol/l)– Metabolic Alkalosis (HCO3

- > 26 mmol/l)• Compensation: the physiological response to an acid-base imbalance

begins with adjustments by the system less involved

Causes of Acid-Base Imbalances

• Respiratory Acidosis– Chronic Obstructive Pulmonary Diseases e.g., emphysema,

pulmonary fibrosis– Pneumonia

• Respiratory Alkalosis– Hysteria– Fever– Asthma

Causes of Acid-Base Imbalances

• Metabolic Acidosis– Diabetic ketoacidosis, Lactic acidosis– Salicylate poisoning (children)– Methanol, ethylene glycol poisoning– Renal failure– Diarrhea

• Metabolic Alkalosis– Prolonged vomiting– Diuretic therapy– Hyperadrenocortical disease– Exogenous base (antacids, bicarbonate IV, citrate toxicity after

massive blood transfusions)

Metabolic Acidosis

Metabolic Alkalosis

Respiratory Acidosis

Respiratory Alkalosis

Electrolyte Balance

Electrolytes have 4 important physiological functions in the body• essential minerals in certain biochemical reactions• control osmosis = control the movement of water between

compartments• maintain acid-base balance• conduct electrical currents (depolarization events)

Regulators:Aldosterone ↑↑↑↑ [Na+] [Cl-] [H2O] ↓↓↓↓ [K+]Atrial Natriuretic Peptide (opposite effect)Antidiuretic Hormone ↑↑↑↑ [H2O] (↓↓↓↓ [solutes])Parathyroid Hormone ↑↑↑↑ [Ca++] ↓↓↓↓ [HPO4

-]Calcitonin (opposite effect)Female sex hormones ↑↑↑↑ [H2O]

Electrolytes

• Sodium (Na+) - 136-146 mmol/liter– Most abundant cation

• major ECF cation (90% of cations present)• determines osmolarity of ECF

– Regulation• Aldosterone• ADH• ANP

– Homeostatic imbalances• Hyponatremia• Hypernatremia

PlasmaOSM = 2[Na+] + 2[K+] + [Urea] + [Glucose]

Hypertonic Alterations - Related to sodium gain or water loss

• Hypernatremia– Serum sodium >146 mmol/L– Intake of hypertonic salt solution– Water movement from the ICF to the ECF

• Intracellular dehydration– Manifestations: in consequence of cell dehydration

• Excitability, convulsions, or on the other hand drowsiness accompanying with pulmonary edema, tachycardia, etc.

• Water deficit- Dehydration (osmotic diuresis at glycosuria (diabetes), gastrointestinal losses-osmotic diarrhea, infectious enteritis, high fever, burn injury, elevated perspiration) - Renal free water clearance- Manifestations:– Tachycardia, weak pulses– Elevated hematocrit and serum sodium level

Hypernatremia

Serum sodium >160 mmol/L in 60 % lethal

Therapy: at water deficit – isotonic solutions (physiological saline solution) or slightly hypotonic (2/3 F)

at normovolemia or hypervolemia – thiazide diuretics(hydrochlorothiazide, decreasing of electrolytes reabsorption in renal tubules) and 5% glucose

frequent monitoring of electrolyte plasma level during the treatment, avoid to fast reestablishment of the electrolyte level (max 1-2 mmol/L/h and 12 mmol/L/day

Hypotonic Alterations - Related to Hyponatremia or free water excess

• Hyponatremia- Serum sodium level <135 mmol/L- decreases the ECF osmotic pressure, and water moves into the cell--- losses of Na+ by GIT (emesis, diarrhea), kidney(hypoaldosteronism, thiazide diuretics), perspiration, burn injury---edema at heart failure, cirrhosis, nephrotic syndrome

- Manifestations: in consequence of brain edema and increase of intracranial pressure

- disorientation, lethargy, apathy, headache, nausea, muscle weakness, coma

• Water Excess- Compulsive water drinking- Syndrome of inappropriate ADH secretion (SIADH)- Manifestations:

- cerebral edema, muscle twitching, headache, and weight gain

Hyponatremia

- water moves into cells based on osmolarity difference, brain cells (neurons) decrease water uptake by compensatory mechanisms decreasing the intracellular osmolarity by elevation of K+ efflux (during 24h), and organic substances metabolism (during 48h, e.g. elimination of polyalcohols, aminoacids, cholin derivates)

Therapy:

the major risk is to fast reestablish the normal level of Na+ ions. The lower osmolarity of neurons due to compensatory mechanisms causes water efflux from the neurons, the neurons will shrink and released from myelin sheath!!!

1. if the disnatremia was developed during the last 48hrs, than fast correction could be made (1-2mmol/L/h)

2. if plasma [Na+] is 105-120 mmol/L and neurological symptoms are present make the correction by 1-2mmol/L/hwithout neurological symptoms the speed of correction could be only 0.5mmol/L/h

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

!

!

Hyponatremia

Calculation of total need of Na+

mmol Na+ = mass (kg) x f x (targeted Na+ - determined Na+)

f = 0.6 for manf = 0.55 for woman

Example: 70 kg weighted man has plasma [Na+] 115 mmol/L, we would like to increase the [Na+] to 127 mmol/L/day (i.e. by 12 mmol/L)

mmol Na+ = 70 x 0.6 x (12) = 504

concentrations of available salt solutions:

0.9% NaCl (physiological saline solution)…1ml = 0.15 mmol Na+ and Cl-10% NaCl ….1ml = 1.7 mmol Na+ and Cl-5.8% NaCl …1ml = 1 mmol Na+ and Cl-4.2% NaHCO3 ….1ml = 0.5 mmol Na+ and HCO3

-

• Chloride (Cl-) - 95-108 mmol/L– Major ECF anion

• helps balance osmotic potential and electrostatic equilibrium between fluid compartments

• plasma membranes tend to be leaky to Cl- anions– Regulation: aldosterone

– Homeostatic imbalances• Hypochloremia - results in muscle spasms, coma (usually

occurs with hyponatremia) often due to prolonged vomiting(elevated sweat chloride diagnostic of Cystic Fibrosis)

Hypochloremia with normonatremia results in metabolichypochloremic alkalosis

Heperchloremia with normonatremia results in metabolichyperchloremic acidosis

Combined disbalances are treated based on the plasma [Na+]

pHdetermined-pHtargeted

Hypochloremia with normonatremia or hypernatremia (e.g. due to administration of drugs with Na+ , such as NaHCO3, Na-lactate, Na-acetate, ..), vomiting at hyperaldosteronism (e.g. at activation of JG cells due to stenosis of renal artery)

1. treatment of the cause, e.g. antiemetics at vomiting2. solution NaCl, KCl at hypokalemia, 4.2% Argininhydrochloride at significant

alkalosis

Calculation of total need of Cl-

mmol Cl- = mass (kg) x 0.3 x BEwhere BE is base excess…. is in the normal range from -2.5 to +2.5 mmol/L, is equal to amount of strong acid (or base) which is needed to titrate 1L of plasma to pH 7.4 at normal pCO2 (5.3 kPa and temp. 37 °C)

in the case, where respiratory compensatory mechanism is involved in regulation of pH (at the alkalosis is �pCO2 due to hypoventilation), then use Nejedly’s formula:

mmol Cl- = mass (kg) x 0.3 x BE x pHdetermined-pHX

7.2487.2637.287.2987.3147.3327.357.3777.3977.4277.4577.4877.5177.5677.617.67pHX

9.598.587.576.565.554.543.532.52pCO2

1. treatment of the cause, obstruction of urinary tract (accompanied with hypernatremia and hyperkalemia), hypoaldosteronism, drug administration e.g. HCl, NH4Cl, lysine-HCl, arginine-HCl), acute diarrhea (accompanied with hypokalemia)

2. treatment of acidosis by NaHCO3

if pH of artery blood is <6.9 apply 100 mmol NaHCO3/2hif pH is from 6.9 to 7.0 apply 50 mmol NaHCO3/1.5h

always check after 1h [K+]

Hyperchloremia with normonatreia

• Potassium (K+)– Major ICF cation, concentration maintained by the Na+/K+ pump

• intracellular 120-125 mmol/L• plasma 3.5-5.5 mmol/L

– Very important role in resting membrane potential (RMP) and in action potentials = essential for transmission and conduction of nerve impulses, normal cardiac rhythms, and skeletal and smooth muscle contraction

• Changes in pH affect K+ balance– Hydrogen ions accumulate in the ICF during states of acidosis. K+

shifts out to maintain a balance of cations across the membrane.

• Aldosterone, insulin, and catecholamines influence serum potassium levels

• Homeostatic imbalances• Hypokalemia• Hyperkalemia

!

• Hypokalemia- Potassium level <3.5 mmol/L- Causes: intake reduction of potassium, and increased loss of potassium (by GIT-vomiting, diarrhea, urinary tract-osmotic diuresis (diabetes), hyperaldosteronism)- Manifestations:

Membrane hyperpolarization causes a decrease in neuromuscular excitability, skeletal muscle weakness, smooth muscle atony, and cardiac dysrhythmias

Estimation of total K+ deficit from plasma [K+] and pH Therapy: severe hypokalemia (<2 mmol/l

requires fast i.v. administration of K+ in form of KCl solution (0.75 mmol/kg/1h, more safety is 20 mmol/h repeatedly, one that dose increases plasma [K+] app. by 0.25mmol/lyou can use a formula to calculate a total need of K+:mmol K+ = 0.3 x mass (kg) x (4.4 - plasma [K+]) + substitution of losses

ECT(L)

losses: mainly by urine = volume x urine [K+]

available solutions: 7.5% KCl (1ml = 1mmolK+), 13.8% KH2PO4 (1ml = 1mmolK+)

these solutions have to be added into glucose solution with max. [K+] 40mmol/l, at max appl. speed 20 mmol/h and max day dose 150 mmol!

• Hyperkalemia- Potassium level >5.5 mmol/L- Caused by increased intake, shift of K+ from ICF (at acidosis),

decreased renal excretion, insulin deficiency, or cell trauma (release of K+

ions)- Mild attacks- Hypopolarized membrane, causing neuromuscular irritability, Tingling

of lips and fingers, restlessness, intestinal cramping, and diarrhea- Severe attacks- The cell is not able to repolarize, resulting in muscle weakness, loss

or muscle tone

Therapy:1. based on antagonistic effect of Ca+ ions on cell membrane (20ml of

10% Ca-gluconicum) 2. appl. of insulin (10-20 IU/h) {stimulates K+ influx into muscle cells}

always with glucose infusion!!! (50g/h)3. diuretics (furosemid) 4. cation exchanger (resonium)5. haemodialysis

Calcium (Ca2+)– Most abundant ion in body

• plasma 2.3-2.6 mmol/L• most stored in bone (98%) as hydroxyapatite

- Necessary for structure of bones and teeth, blood clotting, hormone secretion, and cell receptor function

- Regulation:• Parathyroid Hormone (PTH) - ↑ blood Ca2+

• Calcitonin (CT) - ↓ blood Ca2+

- Homeostatic imbalances:

Hypocalcemia (necrotic pancreatitis, malabsorption, hypoparathyreosis,

vitamin D deficit (osteomalacia)) - muscle cramps, convulsions

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

0.25mmol)

Hypercalcemia (hyperparathyreosis, hypervitaminosis D, osteolytic tumor

metastasis)- vomiting, cardiovascular symptoms, coma (critical [Ca+] is

above 3.75 mmol/l); prolonged � abnormal calcium deposition, e.g.,

stone formation

Therapy: 1.cause, 2. increase of diuresis by furosemide (at 3L/day),

glucocorticoids decreasing Ca+ absorption by intestine, calcitonin

Phosphate (H2PO4-, HPO4

2-, PO43-)

– Important ICF anions; plasma 0.7-1.5 mmol/L• most (85%) is stored in bone as calcium salts• also combined with lipids, proteins, carbohydrates, nucleic acids

(DNA and RNA), and high energy phosphate transport compound• important acid-base buffer in body fluids

– Regulation - regulated in an inverse relationship with Ca2+ by PTH and calcitonin and Vitamin D (If the concentration of one increases, that of the other decreases)

– Parathyroid hormone (PTH) - Increases plasma calcium levels– Vitamin D (fat-soluble steroid) - Increases calcium absorption from the

GI tract– Calcitonin - Decreases plasma calcium levels

– Homeostatic imbalances• Phosphate concentrations shift oppositely from calcium

concentrations and symptoms are usually due to the related calcium excess or deficit

Hypophosphatemia and Hyperphosphatemia

• Hypophosphatemia(abrosia, malnutrition, renal losses, hyperparathyreosis)– Osteomalacia (soft bones)– Muscle weakness– Bleeding disorders (platelet impairment)– Anemia– Leukocyte alterationsTherapy: significant decrease <0.3 mmol/l - for first 3 days 30 mmol,

maintenance dose 10 mmol/davailable solutions: 13.6% KH2PO4 (1ml = 1 mmol K+ and 1 mmol

H2PO4-, 10% Na2HPO4 (1ml = 0.6 mmol Na+, 0.3 mmol HPO4

-2)

• Hyperphosphatemia (renal failure, hyperthyreosis)– High phosphate levels are related to the low calcium levels- Increased neuromuscular excitability (partial depolarization)- Muscle crampsTherapy: decrease of intestine absorption by antacids,

haemodialysis

Magnesium (Mg2+)– 2nd most abundant intracellular electrolyte, 0.8-1.3 mmol/L in plasma

• more than half is stored in bone, most of the rest in ICF (cytoplasm)• important enzyme cofactor; involved in neuromuscular activity, nerve

transmission in CNS, and myocardial functioning– Homeostatic imbalance

• Hypomagnesemia - Associated with hypocalcemia and hypokalemia(abrosia, alcoholism, malabsorption, diarrhea, renal losses) Neuromuscular irritability, Tetany, Convulsions, Hyperactive reflexes vomiting, cardiac arrhythmias, Therapy: at acute stages (cardiac arrhythmias) 20-30 mmol in 200ml 5% glucose per 20 min, mild severe stages per 3h, asymptomatic stages per 24h, repeatedly with frequent level monitoringavailable solution: 10% MgSO4 (1ml = 0.4 mmol Mg+), 10% MgCl2 (1ml = 0.5 mmol Mg+ and 1mmol Cl-)

• Hypermagnesemia – (acute or chronic renal failure, cells trauma), Muscle weakness, Hypotension, Respiratory depression, Lethargy, drowsiness, BradycardiaTherapy: Ca salts as an antagonist, haemodialysis

Acid-Base Balance

• Normal metabolism produces H+ (acidity)

• Three Homeostatic mechanisms: – Buffer systems - instantaneous; temporary– Exhalation of CO2 - operates within minutes; cannot

completely correct serious imbalances– Kidney excretion - can completely correct any imbalance

(eventually)

• Buffer Systems– Consists of a weak acid and the salt of that acid which

functions as a weak base

Acid-Base Balance

• Carbonic Acid - Bicarbonate Buffer– A weak base (carbonic anhydrase)

H+ + HCO3- ⇔⇔⇔⇔ H2CO3 ⇔⇔⇔⇔ H2O + CO2

• Phosphate BufferNaOH + NaH2PO4 ⇔⇔⇔⇔ H2O + Na2HPO4

HCl + Na2HPO4 ⇔⇔⇔⇔ NaCl + NaH2PO4

• Protein Buffer (resp. albumin & hemoglobin )Amino acids have amine group (proton acceptor = weak base) and a carboxyl group(proton donor = weak acid)hemoglobin- oxyhemoglobin systém, where oxyhemoglobin is stronger acid than hemoglobin (proton is more simply released)

- mainly intracellularly, during acidemia proton is bound, during alkalemia proton is released via cell membrane K+/H+ antiporter

Acid-Base balance systems in blood

1. Carbonic Acid - Bicarbonate Buffer 53 %2. Hemoglobin-oxyhemoglobin 35 %3. Plasma proteins 7 %4. Phosphate buffers 5 %

plasma pH 7.37-7.43

Examples:

Prescribe infusion therapy for mineral blood alteration:a) 70 kg man with polyuria 3.5 L/d, plasma [K+] = 2.8 mmol/L, urine

[K+] = 13 mmol/L and with normal levels of other minerals andnormal blood pH

b) 60 kg woman with plasma [Cl-] = 78 mmol/L with normal levels ofother minerals and blood pH 7.52, pCO2 6.5 kPa, BE +4.2 and normal renal function