Fluid
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  • 1. 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. mass of solute mass of solute ×100% = ×100% total mass of solution mass of solute + mass of solvent• Example A 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?
  • 2. 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. moles solute mass ( g ) solute M= = L solution molar mass solute x L 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 Total body water and its distribution in the body compartments. The main functions of water in the human organism.
  • 3. Water Largest single chemical component of the body: 45-75% of body mass Fat (adipose tissue) is essentially water free, so there is relatively more or less water in the body depending on % fat compositionWater is the solvent for most biological molecules within the bodyWater also participates in a variety ofbiochemical reactions, both anabolic andcatabolic Body fat measuring Skinfold Caliper http://www.linear-software.com/online.html
  • 4. 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 processesOther 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
  • 5. 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 ECFOsmolality – the concentrations of solutes in water H2O – solutes will influence the movement of water across membranes π = iRTc Aquaporins- water channel proteins in membranes Net filtration (Starling hypothesis) H2O = 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 capillaryForces favoring filtration - Capillary hydrostatic pressure (blood pressure) - Interstitial oncotic pressure (water-pulling)Forces favoring reabsorption filtration H2O - Plasma oncotic pressure (water-pulling) reabsorption - Interstitial hydrostatic pressure
  • 6. • Electrophoretic separation of plasma proteins • (directly proportional to size and charge)20L/day 60% Mr 67x103 Albumin α1 globulin 1-antitrypsin, 1-acid glycoprotein 4% α2 globulin haptoglobin, 2-macroglobulin, 2-antiplasmin, ceruloplasmin 7% β globulin in plasma the major part forms proteins 65-85 g/l transferin, complement, LDL is formed by colloid particles dissolved in solution 10% 5% fibrinogen Mr340x103 γ globulin = Imunoglobulins IgA, IgD, IgE, IgG and IgM 14% Mr150x103 Water Movement Between the ICF and ECF Oncotic pressure…Colloid osmotic pressure 18L/day
  • 7. 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] }
  • 8. Edema Accumulation of fluid within the interstitial spaces• 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 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
  • 9. Regulating Fluid Intake Thirst Thirst Quenching Wetting the oral mucosa1. 2. (temporary) Stretching of the stomach Decreased blood/body fluid osmolarity = increased hydration (dilution) of the blood is the most important 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
  • 10. 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 failureA 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
  • 11. Osm V PB Factors affecting ADH release ADH Urine osmolarity regulation by ADH ADH
  • 12. Human angiotensinogen is 118 amino acids long Pathway of RAASPrincipal cells & aldosterone
  • 13. Atrial natriuretic peptide 28-amino acid peptide Distribution of SolutesInterstitial fluid isessentially an ultrafiltrateof plasma,water and electrolytes move freely withinthis compartment and between it and theintravascular fluid.Intravascular fluid has almost the samecomposition as interstitial fluid exceptfor its higher protein level.
  • 14. 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
  • 15. 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 levelHypotonic 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
  • 16. 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
  • 17. • 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
  • 18. Electrolytes• Phosphate (H2PO4-, HPO42-, 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
  • 19. 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
  • 20. Acid-Base Balance• Carbonic Acid - Bicarbonate Buffer – A weak base (carbonic anhydrase) H+ + HCO3- ⇔ H2CO3 ⇔ H2O + CO2• Phosphate Buffer NaOH + 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 control changes 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+]
  • 21. Acid-Base Imbalances• Acidosis – High blood [H+] – Low blood pH, <7.35 Alkalosis – 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
  • 22. 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
  • 23. Metabolic AlkalosisRespiratory Acidosis
  • 24. 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]
  • 25. Electrolytes• Sodium (Na+) - 136-146 mmol/liter – Most abundant cation • major ECF cation (90% of cations present) • determines osmolarity of ECF PlasmaOSM = 2[Na+] + 2[K+] + [Urea] + [Glucose] – Regulation • Aldosterone • ADH • ANP – Homeostatic imbalances • Hyponatremia • HypernatremiaHypertonic 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
  • 26. 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/dayHypotonic 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
  • 27. 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/h without 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 HyponatremiaCalculation of total need of Na+ mmol Na+ = mass (kg) x f x (targeted Na+ - determined Na+) f = 0.6 for man f = 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-
  • 28. • 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 metabolic hypochloremic alkalosis Heperchloremia with normonatremia results in metabolic hyperchloremic acidosis Combined disbalances are treated based on the plasma [Na+] 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 vomiting 2. solution NaCl, KCl at hypokalemia, 4.2% Argininhydrochloride at significant alkalosisCalculation of total need of Cl- mmol Cl- = mass (kg) x 0.3 x BE where 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: pHdetermined-pHtargeted mmol Cl- = mass (kg) x 0.3 x BE x pHdetermined-pHXpCO2 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5pHX 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 7.248
  • 29. Hyperchloremia with normonatreia 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 NaHCO3/2h if pH is from 6.9 to 7.0 apply 50 mmol NaHCO3/1.5h always check after 1h [K+]• 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
  • 30. • 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/l you can use a formula to calculate a total need of K+: ECT(L) mmol K+ = 0.3 x mass (kg) x (4.4 - plasma [K+]) + substitution of losses 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
  • 31. 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, calcitoninPhosphate (H2PO4-, HPO42-, 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
  • 32. Hypophosphatemia and Hyperphosphatemia • Hypophosphatemia (abrosia, malnutrition, renal losses, hyperparathyreosis) – Osteomalacia (soft bones) – Muscle weakness – Bleeding disorders (platelet impairment) – Anemia – Leukocyte alterations Therapy: significant decrease <0.3 mmol/l - for first 3 days 30 mmol, maintenance dose 10 mmol/d available 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 cramps Therapy: decrease of intestine absorption by antacids, haemodialysisMagnesium (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 monitoring available 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, Bradycardia Therapy: Ca salts as an antagonist, haemodialysis
  • 33. 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 Buffer NaOH + NaH2PO4 ⇔ H2O + Na2HPO4 HCl + Na2HPO4 ⇔ NaCl + NaH2PO4 - mainly intracellularly, during acidemia proton is bound, during alkalemia proton is released via cell membrane K+/H+ antiporter • 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)
  • 34. Acid-Base balance systems in blood1. Carbonic Acid - Bicarbonate Buffer 53 %2. Hemoglobin-oxyhemoglobin 35 %3. Plasma proteins 7 %4. Phosphate buffers 5 %plasma pH 7.37-7.43Examples: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 and normal blood pHb) 60 kg woman with plasma [Cl-] = 78 mmol/L with normal levels of other minerals and blood pH 7.52, pCO2 6.5 kPa, BE +4.2 and normal renal function