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Sodium (Na+ ):
Sodium is the major cation present in the extra-cellular fluid. Sodium regulates the water balance in the body. The transport of sodium into and out of the cells is very critical for the generation of electrical signals. Many functions in the body such as muscle contraction, nerve impulses require these electrical signals for proper regulation. Any increase or decrease in sodium levels will cause these cells to malfunction. Normal Range of sodium in blood is 135 to 148 milli equivalents/litre. Hyponatremia: Low sodium level state is referred to as Hyponatremia. The main reasons for low sodium levels are: Low dietary intake of sodium, excessive sweating and excessive water intake without adequate sodium compensation. Gastro-Intestinal loses such as diarrhoea. Kidneys help regulate the sodium and water balance. However diuretics can cause the kidneys to excrete more sodium than water, resulting in a low sodium level. The excessive production of anti diuretic hormone also causes the kidneys to excrete more sodium resulting in low levels of sodium. The overproduction of this hormone is seen in conditions such as pneumonia, stroke and due to certain drugs such as carbamazipine. Other disorders that cause low levels of sodium are heart failure, liver failure, poorly controlled diabetes and kidney disorders. Low sodium levels can lead to drowsiness, muscle weakness, seizures. Hypernatremia: High sodium level state is called Hypernatremia Increase in sodium levels are seen in cases of increased loss of water due to exercise and impaired kidney function, when capability of water re-absorption is lost. Hypernatremia is almost always due to dehydration.
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In rare cases hyper natremia also results due to some diuretics which cause excessive loss of water, excessive salt intake without enough water and in case of Cushings syndrome (a condition caused by low level of Anti Diuretic Hormone, as in Diabetes insipidus). The Increased Sodium levels cause the following symptoms: Weak and sluggishness, confusion, paralysis, seizure and coma in extreme conditions Increased levels can lead to increase in blood pressure.
Potassium (K+):
Potassium is the major cation present in the inside the cells. Normal levels of potassium are essential for proper cell function. The major function of potassium in the body includes the regulation of heart beat and muscle function. Normal blood potassium levels are 3.5 to 5.3 milli equivalents/litre. Hypokalemia: Low potassium levels may occur due to 1. diarrhoea and vomiting for a long time. 2. Low dietary intake of potassium 3. Certain diuretics and drugs such as thiazides, used for treating hypertension can cause hypokalemia. 4. Other causes are due to increased sweating, burns, uncontrolled diabetes and diseases associated with GI tract. The Hypokalemia state may lead to weak pulse, low blood pressure and fatigue, muscle weakness and cramps. A very low potassium levels can cause paralysis and abnormal heart rhythms. Hyperkalemia: Increased levels of potassium. Most common cause is the kidney failure and the use of drugs (e.g. ACE inhibitors) that reduce the potassium excretion by the kidney. It can also occur to excessive dietary intake such as potassium rich food and potassium supplements. Some other causes are dehydration, diabetes, injury to tissues, Addisons disease and infection. Symptoms associated with high levels of potassium are abnormal heart rhythm, muscle cramps, pain.
Chloride (Cl-):
Chloride is the major anion in the extracellular fluid. Chloride plays a major role in maintaining the water balance and acid-base balance in the body. Balance of chloride is closely regulated by the body. Normal Range of sodium in blood is 135 to 148 milli equivalents/litre. Hypochloremia: Decreased level of chloride Excessive loss could be due to heavy sweating, vomiting, adrenal gland and kidney disease. Low levels are seen in cases of metabolic acidosis and in salt-losing renal disease. Hypochloremia is seen in cases of diarrhoea, ulcerative colitis, pyloric obstruction, severe burn, heat exhaustion, diabetic acidosis, fever and acute infections such as pneumonia.
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Hyperchloremia: Increase in level of chloride. Increased levels of chloride are seen in case of dehydration, Cushings syndrome, hyperventilation and anemia. Some other causes are diarrhoea, kidney diseases and over activity of parathyroid gland. In case of metabolic acidosis, there is a reciprocal increase in chloride concentration when bicarbonate level drops.
Calcium:
Calcium plays a major role in regulation of the muscle contraction, hormone secretion and membrane permeability. Plasma Calcium exists in three forms: Ionized calcium: Most important Physiologically Active form (45%) Bound calcium: to proteins, principally albumin (40%) Complexed: with phosphate, citrate, sulfate, HC03 (15%) Normal blood ranges for ionized calcium level is 1.13 to 1.31 mmol/L Hypocalcemia: Decrease in body calcium concentration. Calcium decrease is due to alkalosis. Low calcium ensues during wide spread infection in blood and other tissues. Low production of Parathyroid hormone (Hypoparathyroidism) that regulates the level of calcium in the body. Low levels may be due to Vitamin D deficiency. Certain disorders such as hypothyroidism and pancreatitis can also result in low calcium levels. Low calcium level can cause following symptoms: Weakness and Numbness in hand and feet. May cause confusion and seizures. Hypercalcemia: Increase in levels of calcium in the body. Increase in ionized calcium is caused due to acidosis. High level of parathyroid hormone (Hyperparathyroidism) cause increase in levels of calcium. High levels of calcium can be seen in case of high levels of thyroid hormone. High calcium levels can be seen in certain case of bone disorders such as Osteoporosis and Pagets disease. The cancer can lead to increased levels of calcium. The symptoms associated with very high level of calcium are loss of appetite, nausea, vomiting and confusion. In extreme cases person can go into coma and may even be fatal. IONIZED CALCIUM-FREE form of calcium Ionized calcium is the only physiological active form of Calcium. Increased or decreased levels of ionized calcium are directly related to hyperparathyroidism and hypoparathyroidism respectively Acidosis (low pH) causes an increase and alkalosis(high pH)causes a decrease in the amount of ionized calcium. NORMALIZED CALCIUM-bound form of calcium Easylyte reports both Normalized and ionized calcium. Ionized calcium range (Ca++) is based on pH between 7.35 7.45 units (Range Blood Ca++:- 1.13 1.32 mmol/L)-it is reported only at particular pH levels. Normalized calcium is reported at a pH between 7.20 7.60 units (Range Blood Normalized calcium 1.10 1.35) In case of reporting of IONIZED CALCIUM-pH plays a very vital role. pH needs to be reported/considered.
Lithium:
Lithium is normally absent in the body system, and does not metabolize easily. It is administered in the form of carbonate salt to control maniac-depressive disorders. It is believed that lithium cations affect the central nervous system neuro- transmitters, as well as the kidneys. Excessive levels may cause lithium toxicity.
Acid-Base Balance:
An acid is a substance that tends to release H ions in solution A base is a substance that tends to accept H Expressed in terms of pH units. A decrease in pH signifies an increases in H+ and vice versa. Normal arterial pH ranges from 7.35 to 7.45 and it is essential that pH be maintained within these narrow limits for optimal functioning of the human body Severe deviations in systemic acidity can be life threatening Acid-base equilibrium is maintained through the action of buffer systems, the regulation of H and bicarbonate excretion and reabsorption by the kidneys, and the regulation of C02 elimination by the lungs.
Blood gas analysis also called arterial blood gas (ABG) analysis:
Test which measures the amounts of oxygen and carbon dioxide in the blood, as well as the acidity (pH) of the blood. An ABG analysis evaluates how effectively the lungs are delivering oxygen to the blood and how efficiently they are eliminating carbon dioxide from it. The test also indicates how well the lungs and kidneys are interacting to maintain normal blood pH (acid-base balance). Blood gas studies are usually done to assess respiratory disease and other conditions that may affect the lungs, and to manage patients receiving oxygen therapy (respiratory therapy). In addition, the acid-base component of the test provides information on kidney function.
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Blood gas analysis is performed on blood from an artery. It measures the partial pressures of oxygen and carbon dioxide in the blood, as well as oxygen content, oxygen saturation, bicarbonate content, and blood pH. Oxygen in the lungs is carried to the tissues through the bloodstream, but only a small amount of this oxygen can actually dissolve in arterial blood. How much dissolves depends on the partial pressure of the oxygen (the pressure that the gas exerts on the walls of the arteries). Therefore, testing the partial pressure of oxygen is actually measuring how much oxygen the lungs are delivering to the blood. Carbon dioxide is released into the blood as a by-product of cell metabolism. The partial carbon dioxide pressure indicates how well the lungs are eliminating this CO2. The remainder of oxygen that is not dissolved in the blood combines with hemoglobin, a protein-iron compound found in the red blood cells. The oxygen content measurement in an ABG analysis indicates how much oxygen is combined with the hemoglobin. A related value is the oxygen saturation, which compares the amount of oxygen actually combined with hemoglobin to the total amount of oxygen that the hemoglobin is capable of combining with. Carbon dioxide dissolves more readily in the blood than oxygen, primarily forming bicarbonate and smaller amounts of carbonic acid. When present in normal amounts, the ratio of carbonic acid to bicarbonate creates an Acid-base balance in the blood, helping to keep the pH at a level where the body's cellular functions are most efficient. The lungs and kidneys both participate in maintaining the carbonic acid-bicarbonate balance. The lungs control the carbonic acid level and the kidneys regulate the bicarbonate. If either organ is not functioning properly, an acid-base imbalance can result. Determination of bicarbonate and pH levels, then, aids in diagnosing the cause of abnormal blood gas values. The procedure The blood sample is obtained by arterial puncture usually in the wrist or from an arterial line already in place. If a puncture is needed, the skin over the artery is cleaned with an antiseptic. A technician then collects the blood with a small sterile needle attached to a disposable syringe. The patient may feel a brief throbbing or cramping at the site of the puncture. After the blood is drawn, the sample must be transported to the laboratory as soon as possible for analysis ideally in ice bath.
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DEFINITIONS: Metabolic means disturbances in bicarbonate. Respiratory means disturbances in Pc02, the partial pressure of C02 in blood. Acidemia is a state in which the pH is lower than 7.35 Alkalemia is a state in which the pH is greater than 7.45 The terms acidosis and alkalosis refer to physiologic processes or disease states that if not corrected, lead to Acidemia and Alkalemia
Buffer systems:
A buffer is a weak acid or base and its corresponding salt. When a strong acid or base is added to the system, it reacts with the buffer system to form a weaker than the original acid or base. This results in a change in the pH.
Partial Pressure of Gases: For the blood gas measurements, the amount of gas present is expressed in terms of partial pressure. The partial pressure of a given gas is defined as the pressure exerted by that gas alone. The partial pressure of oxygen could be measured by removing nitrogen, carbon dioxide, and water vapour, and determining the pressure resulting from the remaining oxygen molecules. This is a tedious procedure, which we can circumvent, either by the use of other types of measuring instruments (special electrodes, etc.) or by calculation.
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pressure is necessary to maintain a 50% oxygen saturation. This indicates a decreased affinity. Conversely, a lower P50 indicates a leftward shift and a higher affinity.
RENAL SYSTEM:
The kidneys regulate the acid-base balance by adjusting HC03 (Bicarbonate). An increase in C02 results in H excretion and synthesis of HC03. Example, C02 + H20 H2C03 (which dissociates into) H and Hc03 H ions are exchanged for Na ions and acidic urine is then excreted. HC03 and Na return to ECF to restore normal blood pH. This mechanism is inhibited by Na deficiency. When the ECF becomes alkalemic, then, kidneys conserve H and excrete HC03. This mechanism is inhibited by Na and K deficiency Arterial Blood Gas (ABG) analysis provides information through laboratory measurements to assess acid-base status Metabolic acidosis is a physiologic process of absolute or relative increase in acid concentration. Simple uncompensated is HC03 <25mMol/L. Strong acids react with NaHC03 to form Na and H2C03. This reaction consumes HC03.
Anion Gap:
The difference in concentration between measured cations and the anions. The total number of anions and Cations is roughly the same. There are some unmeasured cations and anions, which contribute to the ionic component of blood. The measured cations, are usually greater than the measured anions by about 8 to 16 mmol/l. This is because unmeasured anions constitute a significant proportion of total number of anions. The proteins make this up predominantly. The other contributors are sulphates, phosphates, lactates, and ketones. Anion Gap is calculated as follows: AG= {Na} {Cl} + {HC03}. Raised Anion Gap: Causes for raised anion gap include dehydration and any cause due raised immeasurable anions like lactate, ketones and renal acids. It may also be due to treatment with drugs such as penicillin, salicylates, and poisoning with methanol, ethanol, and paraldehyde. Decreased Anion Gap: The cause for decreased anion gap includes hypoalbuminemia and severe hemodilution. Some of the rare cause includes increase in minor cation concentration like calcium and magnesium. Limitations include not being a helpful measure in the mixture of acidosis such as lactic acidosis and renal tubular acidosis, and hypoalbuminemia needs a correction factor
Respiratory Alkalosis:
Respiratory alkalosis is a condition where the amount of carbon dioxide found in the blood drops to a level below normal range. This condition produces a shift in the body's pH balance and causes the body's system to become more alkaline (basic). This condition is brought on by rapid, deep breathing called hyperventilation. This rapid, deep breathing can be caused by conditions related to the lungs like pneumonia, lung disease, or asthma. More commonly, hyperventilation is associated with anxiety, fever, drug overdose, carbon monoxide poisoning, or serious infections.
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This symptom is accompanied by dizziness, light headedness, agitation, and tingling or numbing around the mouth and in the fingers and hands. Muscle twitching, spasms, and weakness may be noted. Seizures, irregular heart beats, and tetany (muscle spasms so severe that the muscle locks in a rigid position) can result from severe respiratory alkalosis.
Respiratory acidosis:
Respiratory acidosis is a condition in which a build-up of carbon dioxide in the blood produces a shift in the body's pH balance and causes the body's system to become more acidic. This condition is brought about by a problem either involving the lungs and respiratory system or signals from the brain that control breathing. Respiratory acidosis can be caused by diseases or conditions that affect the lungs themselves, such as emphysema, chronic bronchitis, asthma, or severe pneumonia. Blockage of the airway due to swelling, a foreign object, or vomit can induce respiratory acidosis. Conditions that cause chronic metabolic alkalosis can also trigger respiratory acidosis. The most notable symptom will be slowed or difficult breathing. Headache, drowsiness, restlessness, tremor, and confusion may also occur. A rapid heart rate with changes in blood pressure may be observed.
Metabolic Alkalosis:
Metabolic alkalosis can result from the loss of acid, addition of alkali or both in the Kidneys or elsewhere. Non Renal causes may include stomach (loss of acid). Redistribution of alkali from the intracellular stores to the ECF (as in K or Cl depletion). The other reasons are due to oral administration of antacids, ion-exchange resins, milk alkali syndrome, oral bicarbonate and parenteral administration of alkali (citrate in blood transfusions, bicarbonate in severe metabolic acidosis). Renal causes of alkali excess include mineralocorticoid excess. Response to long-standing hypercapnia (persists even after correction of respiratory acidosis). Hypokalemia (promotes H+ secretion in the distal nephron) and ECF volume depletion due to impaired bicarbonate excretion. Certain conditions can cause metabolic alkalosis by a number of mechanisms (e.g. diuretic use causes both ECF depletion and hypokalemia).
Metabolic acidosis:
Metabolic acidosis can be due to a variety of conditions. A number of conditions can result in metabolic acidosis, the most important among them being the under perfusion of tissues resulting in accumulation of lactic acid. Differentiation of the causes of metabolic acidosis requires the estimate of an entity called the anion gap. Three major sources are: Renal failure unable to secrete acidic waste Ketosis overproduction of ketones in untreated diabetes Lactic acidosis in conditions in which there is a lack of oxygen in tissues.
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Temperature Correction: Closed-system blood sample has fixed oxygen and carbon dioxide contents, but manifests different gas tensions as the temperature of the sample varies. When caring for hyper- or hypothermic patients, it is appropriate to determine the gas tensions actually existing in the patient at the abnormal body temperature. Such logic leads to the practice of "temperature corrected" pH, pCO2 and pO2 values.
Bicarbonate (HCO3-):
Plasma bicarbonate [HCO3] is the value for plasma bicarbonate calculated with Henderson-Hassel Balch equation after entering the pH and pCO2 measured values. log10[HCO3] = pH + log10pCO2 - 7.604
Standard bicarbonate:
Standard bicarbonate is the bicarbonate concentration in plasma in a completely oxygenated blood sample equilibrated with pCO2 of 40 mm Hg at 37C excluding the influence of respiratory factor and indicating metabolic disorder.
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The base excess of the extracellular fluid is constant during acute in-vivo changes in pCO2 and hence the best parameter of a pure metabolic (non-respiratory) acid-base disturbance. It is often called the Standard Base Excess.
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Hematocrit:
Hematocrit is the ratio of the volume of packed red blood cells to the total blood volume and is therefore also known as the packed cell volume, or PCV. The Hematocrit is reported as a percentage or a ratio.
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Terminology used electrolytes and blood gas analyzers: Ion selective electrodes:
The electrodes are electrolytic substances that are selectively permeable to
specific ions. Their specificity helps in utilizing them for analysis of critical ions in the human system. Ion Selective Electrodes (ISE) is membrane electrodes that respond selectively to ions in the presence of others. These include probes that measure specific ions and gasses in solution. The most commonly used ISE is the pH probe. An Ion Selective Electrode measures the potential of a specific ion in solution. (The pH electrode is an ISE for the Hydrogen ion.) This potential is measured against a stable reference electrode of constant potential. The potential difference between the two electrodes will depend upon the activity of the specific ion in solution. This activity is related to the concentration of that specific ion, therefore allowing the end-user to make an analytical measurement of that specific ion. Several ISE's have been developed for a variety of different ions.
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Calibration:
Standard solutions of known concentrations are measured by the analyzer. The mV reading of each standard solution is noted and a curve of concentration vs. mV reading is plotted. Now the unknown solution can be measured. The mV value of the unknown solution is then calculated and corresponding solution concentration is determined. In ISE measurements, this is achieved by measuring the electrode response in a series of standard solutions and plotting a Calibration Graph of electrode potential (mV) versus activity or concentration in two or more standard solutions. This graph will have mV on a normal y-axis and concentration (activity), Moles, on a logarithmic x-axis.
Slope:
The gradient of the line formed by plotting the electrode response in millivolts against the logarithm of the activity (or concentration) of the measured ion.
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milliVolts
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Concentration (mmol/l)
Reproducibility:
A measure of the closeness of replicate measurements of the same test solution using the same measurement techniques and under the same conditions. See Precision. Reproducibility can be affected by a number of factors including instrument or electrode instability, electrode drift, frequency of calibration, temperature variation, loss of sample, contamination.
Reference electrode:
That part of an electrode measuring system, which provides a constant stable voltage regardless of the composition of the external solution. This voltage is used as the base from which the sample-induced changes in potential of the ISE are measured.
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Membrane:
A continuous layer covering a structure or separating two electrolytic solutions. The membrane of an ISE is responsible for the potential response and the selectivity of the electrode.
Drift:
The slow change in the measured potential of an electrode pair. When the electrodes are first immersed in a new solution, there is initially a relatively rapid change in the potential, which gradually decreases as the ions in solution come into equilibrium with those passing through the ion-selective membrane. Normally after two or three minutes, a stable condition is achieved.