Part 1 Electrolytes. Electrolytes Electrolytes are ions capable of carrying an electricl charge Anions: (-) → Anode Cations: (+) → Cathode Major cations.

Part 1

ElectrolytesElectrolytes

ElectrolytesElectrolytes

Electrolytes are ions capable of carrying an electricl charge Anions: (-) → Anode Cations: (+) → Cathode

Major cations of the body Na+, K+, Ca+2 & Mg+2

Major anions of the body Cl-, HCO3

-, HPO4-2 & SO4

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M. Zaharna Clin. Chem. 2009

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Essential Component in Numerous Essential Component in Numerous processesprocesses

1. Volume and osmotic pressure (Na+, K+, Cl-)2. Myocardial rhythm and contraction (K+, Mg2+,

Ca2+)3. Cofactors in enzyme activation (Mg2+, Ca2+,

Zn2+).4. Regulation of ATPase ion pump (Mg2+)5. Acid/Base balance (pH) (HCO3

-, K+, Cl-)

6. Coagulation (Mg2+, Ca2+)7. Neuromuscular (K+, Mg2+, Ca2+)

The body has complex systems for monitoring and maintaining electrolyte concentrations


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Maintenance of water homeostasis is vital to life for all organisms

Maintenance of water distribution in various body fluids is a function of electrolytes (Na+, K+, Cl- & HCO3

-)


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WaterWater

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 → sweating

Water is located in intracellular and extracellular compartments


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WaterWaterNormal plasma ~ 93 % H2O, the rest is

mixture of Lipids and proteins.Concentration of ions within the cells and

plasma is maintained by:1.Energy consumption: Active transport 2.Diffusion: Passive transport

Maintaining 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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OsmolalityOsmolality

Physical property of a solution 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 SignificanceClinical Significance

Osmolality is the parameter to which hypothalmus responds to maintain fluid intake.

The regulation of osmolality also affects the Na+ concentration in plasma90% of osmotic activity in plasma

Another process affects Na+ concentration is regulation of blood volume.


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Clinical significanceClinical 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 LoadWater Load

Excess intake of water lower plasma osmolality

Kidney is important in controlling water excess

AVP 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 deficitWater 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 Regulation of blood volumevolume

Blood volume essential in maintaining blood pressure and ensure perfusion to all tissue and organs.

Regulation of both sodium & water are interrelated in controlling blood volume

Renin-angiotensin-aldosterone: system of hormones that respond to decrease in blood volume and help maintain the correct blood volume.


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Changes in blood volume detected by receptors in:

the cardiopulmonary circulation , carotid sinus, aortic arch and glomerular arterioles

They activate effectors that restore volume by:

appropriately varying vascular resistance, cardiac output, and renal Na and H2O retention.


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Angiotensin converting enzyme (ACE)

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Other Factors effecting blood volume:

1. Atrial natriuretic Peptide (ANP) → sodium excretion → ↓ blood volume

2. Volume receptors → release of AVP → conserve water → ↑ blood volume

3. Glomerular filtration rate (GFR) ↑ in volume expansion and ↓ in volume depletion


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Determination of Determination of OsmolalityOsmolality

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 pointVapor pressure


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Determination of Determination of OsmolalityOsmolality

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 GapOsmolal GapOsmolal gap is the difference between the

measured osmolality and the calculated one.

Osmolal Gap= measured osmolality - calculated osmolality

The 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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SodiumSodiumMost abundant extracellular cation- 90%Major function is maintaining the normal

water distribution & osmotic pressure of plasma

Role 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 Regulation of Sodium BalanceBalance

Plasma Na+ concentration depends: on the intake and excretion of water and, on the renal regulation of Na+

Three processes are of primary importance: 1.intake of water in response to thirst (p. osmolality)

2.the excretion of water (AVP release)3.the blood volume status, which affects Na+ excretion through aldosterone, angiotensin II, and ANP (atrial natriuretic peptide).


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NephronNephron

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Regulation of Sodium Regulation of Sodium BalanceBalance

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 Aldosterone

Renin-Angiotensin systemAtrial natriuretic Peptide (ANP) → sodium excretion


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HyponatremiaHyponatremia

Defined as a serum/plasma level less than 135 mmol/L.

One of the most common electrolyte disorders in hospitalized and non-hospitalized patients

Levels below 130 mmol/L are clinically significant.


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HyponatremiaHyponatremia


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HypernatremiaHypernatremia

Hypernatremia: increased sodium concentration > 145 mmol/l

Result of excess water loss in the presence of sodium excess, or from sodium gain


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Sodium determinationSodium determination

Methods:1. Flame emission

spectrophotometry2. Atomic absorption

spectrophotometry3. Ion Selective electrode


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Atomic absorption Atomic absorption spectrophotometryspectrophotometry


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Ion Selective electrodeIon Selective electrode


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PotassiumPotassiumMajor 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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Effects on Cardiac Effects on Cardiac musclemuscle

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

Decrease extracellular potassium; decrease excitability


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Potassium Role in Hydrogen Potassium Role in Hydrogen ConcentrationConcentration

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 Regulation of potassiumpotassium

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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HypokalemiaHypokalemia

Decrease of serum potassium below 3.5 mmol/l


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HyperkalemiaHyperkalemia Increase potassium serum levels > 5 mmol/l Associated with diseases such as renal and

metabolic acidosis


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Potassium Potassium determinationdetermination

Assay method: Ion selective Electrode a valinomycin membrane is

used to selectively bind K+


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ChlorideChloride

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.M. Zaharna Clin. Chem. 2009

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ChlorideChlorideCl– 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 sweat.

Excessive sweating stimulates aldosterone secretion, which acts on the sweat glands to Conserve Na and Cl–.


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Electric NeutralityElectric Neutrality

Sodium/chloride shift maintains equilibrium within the body.

1. Na reabsorbed with Cl in proximal tubules.2. Chloride shift

In 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 shiftChloride shift

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HypochloremiaHypochloremiaHypochloremia: < 98 mmol/l


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HypercholremiaHypercholremia

Hypercholremia: > 109 mmol/l


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AssayAssay

1. Coulometric titration (ref. method)2. Ion selective electrode


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Part 1 Electrolytes. Electrolytes Electrolytes are ions capable of carrying an electricl charge Anions: (-) → Anode Cations: (+) → Cathode Major cations.

Documents

distribution of water

water absorption

suppressed water

water deficit

water intake avp

water excess avp

water normal plasma

renal water regulation