Part 1 Electrolytes Lecture 14 - PowerPoint Presentation

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Part 1

Electrolytes

Lecture 14

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Electrolytes

Electrolytes are ions capable of carrying an electricl chargeAnions: (-) → AnodeCations: (+) → CathodeMajor cations of the bodyNa+, K+, Ca2+ & Mg2+Major anions of the bodyCl-, HCO3-, HPO42- & SO42-

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Cathode

Anode

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Essential Component in Numerous processes

Volume and osmotic pressure (Na+, K+, Cl-)Myocardial rhythm and contraction (K+, Mg2+, Ca2+)Cofactors in enzyme activation (Mg2+, Ca2+, Zn2+).Regulation of ATPase ion pump (Mg2+)Acid/Base balance (pH) (HCO3-, K+, Cl-)Coagulation (Mg2+, Ca2+)Neuromuscular (K+, Mg2+, Ca2+)The body has complex systems for monitoring and maintaining electrolyte concentrations

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Water

Maintenance of water homeostasis is vital to life for all organismsMaintenance of water distribution in various body fluids is a function of electrolytes (Na+, K+, Cl- & HCO3-)

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Water

Average water content of human body is 40-75% of total body weight.Solvent for all body processesTransport nutrients to cellsRegulates cell volumeRemoves waste products → urineBody Coolant → sweatingWater is located in intracellular and extracellular compartmentsIntracellular fluid (ICF) is the fluid inside the cellsExtracellular fluid (ECF) and subdivided into theintravascular extracellular fluid (plasma) and the interstitial cell fluid that surrounds the cells in the tissue

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Water

Normal plasma ~ 93 % H2O, the rest is a mixture of Lipids and proteins.Concentration of ions within the cells and plasma is maintained by:Energy consumption: Active transport Diffusion: Passive transportMaintaining conc. of electrolytes affect distribution of water in compartments.Most membranes freely permeable to water.Conc. of ions on one side affect flow of water across the membrane.

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Osmolality

Physical property of a solution is based on the concentration of solutes per kilograms of solvent (mOsm/Kg)Sensation of thirst & arginine vasopressin hormone (AVP) [formerly, Antidiuretic hormone (ADH)] are stimulated by hypothalamus in response to increased blood osmolalityThirst → more water intakeAVP → increase water absorption in kidney

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Clinical Significance

Osmolality is the parameter to which hypothalamus responds to maintain fluid intake.The regulation of osmolality also affects the Na+ concentration in plasmaaccount for ~90% of osmotic activity in plasmaAnother process which affects Na+ concentration is regulation of blood volume.

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Clinical significance

To maintain normal plasma osmolality (275-295 mOsm/Kg) hypothalamus must respond quickly to small changes 1-2% increase in osmolality: 4 fold increase in AVP secretion.1-2% decrease in osmolality: shuts off AVP secretion.Renal water regulation by AVP and thirst play important roles in regulating plasma osmolality. Renal water excretion is more important in controlling water excess, Whereas thirst is more important in preventing water deficit or dehydration. Consider what happens in several conditions.

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Water Load

Excess intake of water lower plasma osmolalityKidney is important in controlling water excessAVP and thirst are suppressedWater is not reabsorbed, causing a large volume of dilute urine to be excreted Hypoosmolality and hyponatremia usually occur in patients with impaired renal excretion of water

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Water deficit

As a deficit of water, plasma osmolality begins to increase.Both AVP secretion and thirst are activated. Although AVP contributes by minimizing renal water loss, thirst is the major defense against hyperosmolality and hypernatremia. A concern in infants, unconscious patients, or anyone who is unable to either drink or ask for water.

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Regulation of blood volume

Blood volume is essential in maintaining blood pressure and ensure perfusion to all tissues and organs.Regulation of both sodium & water are interrelated in controlling blood volumeRenin-angiotensin-aldosterone: system of hormones that respond to decrease in blood volume and help maintain the correct blood volume.

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Regulation of blood volume

Changes in blood volume is detected by receptors in: the cardiopulmonary circulation , carotid sinus, aortic arch and glomerular arterioles

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They activate effectors that restore volume by:

appropriately varying vascular resistance,

cardiac output,

and renal Na and H

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O retention.

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Angiotensin

converting enzyme (ACE)

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M. Zaharna Clin. Chem. 2009

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Regulation of blood volume

Other Factors effecting blood volume: Atrial natriuretic Peptide (ANP) → sodium excretion →  blood volumeVolume receptors →  release of AVP → conserve water →  blood volumeGlomerular filtration rate (GFR):  in volume expansion and  in volume depletion

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Increase in Blood Volume

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Determination of Osmolality

Serum or urine sample (plasma not recommended due to the use of anticoagulants)Based on properties of a solution related to the number of molecules of solutes per kilogram of solvent such as:Freezing point ( osmolality freezing point temp.)Vapor pressure ( osmolality  Vapor pressure)

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Determination of Osmolality

Freezing Point Osmometer:Standardized method using NaCl reference solution.Specimen is supercooled to -7ºC, to determine freezing point osmolality causes depression in the freezing point temp. More solutes present the longer the specimen will take to freeze.

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Osmolal

Gap

Osmolal gap is the difference between the measured osmolality and the calculated one.Osmolal Gap= measured osmolality - calculated osmolalityThe osmolal gap indirectly indicates the presence of osmotically active substances other than sodium, urea or glucose. (ethanol, methanol or β-hydroxybutyrate)

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Case Study

A sixty-seven year old white male was found pulseless and resuscitated; then brought to the emergency room. He had been reported to be drinking in a bar all afternoon, and had then fallen from a ten foot balcony to snow covered ground. He arrived in the emergency room with a fractured occiput and was unresponsive.Admission Lab. results:

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Na=143

mEq

/l

(

136-145)

BUN=4 mg/

dL

(6 – 20)

pH=7.30

(7.35 – 7.45)

Cl=105

mEq

/l

(

95-105)

GLU=104 mg/dL

Osmolality=356

mOsm

/kg

(275 – 295)

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Case Study

Cal. Osmo. = (2 X 143) + (104/20) + (4/3) = 286 + 5.2 + 1.33 = 293Osmolal Gap= measured osmolality - calculated osmolality = 356 – 293 = 63An OG value greater than 15 is considered a critical valueThe presence of low blood pH, elevated anion gap and greatly elevated OG is a medical emergency that requires prompt treatment

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M. Zaharna Clin. Chem. 2009

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Na

+

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Sodium

Most abundant extracellular cation- 90%Major function is maintaining the normal water distribution & osmotic pressure of plasmaRole in maintaining acid-base balance (Na+, H+ exchange mechanism)Normal range Serum: 136-145 mmol/LATPase ion pump: the way the body moves sodium and potassium in and out of cells.3 Na+ out of the cell for every 2 K + in and convert ATP to ADP.

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Regulation of Sodium Balance

Plasma Na+ concentration depends: on the intake and excretion of water and, on the renal regulation of Na+Three processes are of primary importance: Intake of water in response to thirst ( p. osmolality)The excretion of water (AVP release)The blood volume status, which affects Na+ excretion through aldosterone, angiotensin II, and ANP (atrial natriuretic peptide).

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Nephron

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Regulation of Sodium Balance

70 % of sodium that is filtered is reabsorbed in proximal tubules.Remainder occurs in the ascending loop of Henle (without water absorption) & DCT under regulation of: AldosteroneRenin-Angiotensin systemAtrial natriuretic Peptide (ANP) → sodium excretion

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Hyponatremia

Defined as a serum/plasma level less than 135 mmol/L.One of the most common electrolyte disorders in hospitalized and non-hospitalized patientsLevels below 130 mmol/L are clinically significant.

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Causes of Hyponatremia

The principal clinical concern of hyponatremia is the encephalopathy associated with acute-onset severe hyponatremia and consequent cerebral edema. 

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Hypernatremia

Hypernatremia: increased sodium concentration > 145 mmol/lResult of excess water loss in the presence of sodium excess, or from sodium gain

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With severe elevations of sodium, seizures and coma may occur.

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Sodium determination

Methods:Flame emission spectrophotometrymeasurement of light emitted when the element is excited by energy in the form of heat.

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Atomic absorption spectrophotometry

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Ion Selective electrode

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Reference electrode

selective membrane at the ion selective electrode, allows measured ions to pass, but excludes the passage of the other ions

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Potassium

Major intracellular cation20 X greater concentration in the cell vs. outside.2% of the bodies potassium circulates within the plasma.Function:Regulates neuromuscular excitabilityHydrogen ion concentrationIntracellular fluid volume

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K

+

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Effects on Cardiac muscle

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Ratio of K

+

intracellular & extracellular is important determinant of resting membrane potential across cell membrane

Increase plasma potassium; decreasing the resting membrane potential, increase excitability, muscle weakness

decreases the net difference between the cell’s resting potential and threshold (action) potential

Decrease extracellular potassium; decrease excitability

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Potassium Role in Hydrogen Concentration

In hypokalemia (low serum K+), As K+ is lost from the body, Na+ and H+ move into the cell. The H+ concentration is, therefore, decreased in the ECF, resulting in alkalosis.

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Regulation of potassium

The kidneys are important in the regulation of K+ balance.Initially, the proximal tubules reabsorb nearly all the K+. Then, under the influence of aldosterone, K+ is secreted into the urine in exchange for Na+ in both the distal tubules and the collecting ducts. Thus, the distal tubule is the principal determinant of urinary K+ excretion. Most individuals consume far more K+ than needed; the excess is excreted in the urine but may accumulate to toxic levels if renal failure occurs.

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Hypokalemia

Decrease of serum potassium below 3.5 mmol/l

Insulin promotes acute entry of K into skeletal muscle and liver by increasing Na, K-ATPase activity;

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Hypermineralocorticoid-like effects. In the kidney, cortisol activation of mineralocorticoid receptors alters renal tubular exchange of sodium (retained), potassium (excreted)

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Hyperkalemia

Increase potassium serum levels > 5 mmol/lAssociated with diseases such as renal and metabolic acidosis

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Potassium determination

Assay method:Ion selective Electrodea valinomycin membrane is used to selectively bind K+

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Chloride

Major extracellular anionCl– is involved in maintaining: osmolality, blood volume, and electric neutrality.In most processes, Cl– ions shift secondarily to a movement of Na+ or HCO3–.Cl– ingested in the diet is Completely absorbed by the intestinal tract.

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Cl

-

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Chloride

Cl– ions are filtered out by the glomerulus and passively reabsorbed, in Conjuction with Na, by the proximal tubules.Excess Cl– is excreted in the urine and sweatExcessive sweating stimulates aldosterone secretion, which acts on the sweat glands to Conserve Na+ and Cl–

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Electric Neutrality

Sodium/chloride shift maintains equilibrium within the body.Na reabsorbed with Cl in proximal tubules.Chloride shiftIn this process, carbon dioxide (CO2) generated by cellular metabolism within the tissue diffuses out into both the plasma and the red cell. In the red cell, CO2 forms carbonic acid (H2CO3), which splits into H+ and HCO3- (bicarbonate). Deoxyhemoglobin buffers H+, whereas the HCO3- diffuses out into the plasma and Cl- diffuses into the red cell to maintain the electric balance of the cell

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Chloride shift

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Hypochloremia

Hypochloremia: < 98 mmol/l

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Hypercholremia

Hypercholremia: > 109 mmol/l

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Assay

Coulometric titration (ref. method)measure amount of analyte by measuring amount of current and time required to complete reaction use Ag electrode to produce Ag+Ag (s) » Ag+ + e-Ag+ + Cl- » AgCl Ion selective electrode

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