Body Fluid Compartments DR. ABDULRAHMAN AL-AJLAN

Body fluid compartments: The major body fluid is water, roughly 70% of normal persons body weight is water.  There are two main body compartments;  1- The intracellular fluid compartment (ICF).  2- The extracellular fluid compartment (ECF).  ICF is the volume of fluid inside the cells, and ECF is that volume of fluid which lies outside cells. There are major differences between the chemical composition of the intra and extracellular fluids. E.g. Sodium (Na+) is the principal extracellular cation and the K+ the principal intracellular cation.

Electrolytes Electrolytes are positively and negatively charged ions which are in solution in all body fluids. It is called electrolytes because of their charge and consequent movement in an electrical field.

The major electrolytes are as follows: Sodium (Na+), potassium K+, chloride Cl-, calcium (Ca+2), magnesium (Mg+2), bicarbonate (HCO3-), phosphate (Po4-2), and sulfate (So2-4). The concentrations of these ions in the bloodstream remain fairly constant throughout the day in a healthy person. Changes in the concentration of one or more of these ions can occur during various acute and chronic disease states and can lead to serious consequences Inside cells the main anions are protein and phosphate.  Cl- and bicarbonate (HCo- 3) are main anions in ECF.

Sodium (Na+): Sodium is the major positive ion of the ECFs (out side of the cell). The concentration of Na+ inside cells is only 5 mmol/L compared to 140 outside. The sodium content of the blood is a result of balance between dietary intake and renal excretion.

Function of Na+:  Na+ plays an important role in maintains normal plasma pH. Helps regulate blood pressure and water balance in cells. Na+ is essential for the production of hydrochloric acid in the stomach. Na+ is crucial in transporting amino acids across cell membrane.

Factors affect sodium levels  1-Steroid hormone (aldosterone) which decreases loss of Na+ in the urine. Aldosterone increases the reabsorption of Na+ and the excretion of K+ by the distal tubules in the kidney. Mean that aldosteron regulates renal Na+ loss and controls the Na+ content of ECF. 2- Atrial natriuretic peptide (ANP) is a hormone secreted from the heart that increases Na+ loss from the body.

It is play a minor role in the regulation of ECF volume and Na+ con.  Source of Na+ : The most common source of Na+ is table salt and Na+ is found in varying amounts in all food. Salt is sodium chloride (about 40% of salt is Na+ and 60% chloride). Normal results:  The normal level of serum sodium is in the range of 136-145 mM. The normal levels of serum potassium are 3.5-5.0 mM. Note that sodium occurs at a much higher concentration than potassium.

Abnormal results:- High serum sodium levels (hypernatremia) occur at sodium concentrations over 145 mM, with severe hypernatremia over 152 mM. Hypernatremia is usually caused by diseases that cause excessive urination. In these cases, water is lost, but sodium is still retained in the body. The symptoms include confusion and can lead to convulsions and coma.

Hyponatremia:  Low serum sodium levels (hyponatremia) are below 130 mM, with severe hyponatremia at or below 125 mM. Hyponatremia often occurs with severe diarrhea, with losses of both water and sodium, but with sodium loss exceeding water loss. Hyponatremia provokes clinical problems only if serum sodium falls below 125 mM, especially if this has occurred rapidly. The symptoms can be as mild as tiredness but may lead to convulsions and coma.

Potassium K+ is the major (Principal) intracellular cation in the body, with 20 time's greater con inside the cells than out side. The average human body 70 Kg contains 3.6 moles of K+. most of this is inside cells. 80% of intracellular K+ is in muscle tissue. The normal con of K+ in the plasma is about 4.5 m mole /L which is low compared with the Na level of 140 m mol/L.

Function of K+ Regulation of neuromuscular excitability. Regulation of contraction of the heart Regulation of intracellular fluid volume Regulation of hydrogen ion con.

In hypokalemia (low serum K+), as K+ ions are lost from the body, Na+ and H+ ions move into the cell, the H+ ion con is decrease in the ECF, resulting in alkalosis. If K+ levels are very high, the heart stops beating in diastole (the fully relaxed state). If the K+ is very low, the heart stops beating in systole (tightly contracted state). Mean that the K+ ion con has a major effect on the contraction of cardiac muscle.

Factors affect K+ levels: There are several important factor that influence the distribution of K+ between cells and ECF  K+ loss when the Na+- K+ ATP ase pump is inhibited by conditions such as hypoxia, hypomagnesemia. Insulin promotes entry of K+ ions into skeletal muscle and liver by increasing Na-K-ATP ase activity. Cathecholamines, such as epinephrine promote cellular entry of K+

Hyperkalaemia It is the commonest and most serious electrolyte emergency encountered in clinical practice. Above 7.0 mmol/ L there is a serious risk of cardiac arrest. This it is important to check the serum K+ con in patients after cardiac arrest.

The causes of hyperkalaemia include:  Kidney failure (decrease excretion of K+, anuria compete, shut down of kidney function). Tissue damage such as crush injuries, with damage to large volume of muscle tissues, and massive hemolysis. Exercise (violent muscle contraction, K+ is released from muscle during exercise, which may increase plasma K+ by 0.3 to 1.2 mmol/L with mild to moderate exercise and by as much as 2.0 to 3.0 mmol/L with vigorous execise. D.M, Insulin deficiency promotes cellular loss of K+.  Addison s disease (primary adrenal insufficiency). In the absence of aldosteron, the exchange of Na+ and K+ in the kidney is reduced, with increase loss of Na and retention of K+ in body. Low serum Na+ and high K+ are characteristic of this disease.

Symptoms of hyperkalaemia:  It can cause muscle weakness by altering neuromuscular conduction ( it is develop when K+ reaches 8.0 mmol/L. It disturbs cardiac conduction, which can lead to cardiac arrest (when con more than 10 mmol/L) Plasma con 6.o to 7.0 mmol/ may alter the electrocardiogram (ECG)

Treatment: Treatment for acute hyperkalaemia is  The infusion of insulin and glucose to move K+ ions into cells. An infusion of calcium gluconate may also be given to counteract the effects of hyperkalaemia. Dialysis is necessary to treat sever hyperkalaemia.

Hypokalaemia It is defined as a plasma K+ con below the lower limit of the reference range. The causes of hypokalaemia include:  Gastrointestinal losses (prolonged diarrhea or vomiting). Renal losses (may be due renal disease or increased aldosterone production) Aldosteron promotes Na retention and K+ loss.  3- Decreased Mg (promotes cellular and renal loss of K+) magnesium deficiency diminishes the activity of Na- K+ ATP ase and enhances the secretion of aldosterone. Low dietary intake of K+ rarely causes hypokalaemia in healthy persons.

Treatment: It is treatment by oral or intravenous K+ (I.V) K salts are unpleasant to take orally and usually given prophylactically in an enteric coating). I.V K+ should not be given faster than 20 mmol/h except in extreme cases and under ECG monitoring.  Remark : In mild hypokalemia may be corrected simply by including food with a high K+ content, such as bananas and orange juice in the diet.

Collection of samples: Proper collection and handling of samples for K+ analysis is extremely important. There are many causes of artifactual hyperkalemia. Coagulation process release K+ from platelets (serum K+ may be 0.1 to 0.5 mmol/L higher than plasma K+ con. This situation may be avoided by using a heparinized tube to prevent cloting of the specium. In thrombocytosis serum K+ may be elevated.(by using proper care in the drawing of blood) If a toukniquet is left on the arm too long during blood collection may be release K+ into plasma.

To avoided artifactual hyperkalemia, whole blood samples for K+ determinations should be stored at room temperature (never ice) Hemolysis must be avoided because of the high K+ content of erythrocytes. Heparin is the anti coagulant of choice. Serum, plasma and urine may be acceptable for analysis. Urine specimens should be collected over a 24 hour period to eliminate the influence of diurnal variation. Reference range for K+ : Plasma, serum 3.4 - 5.0 mmole/L Urine (24h) 25 – 125 mmol/24h

Chloride (Cl-) Chloride is the major extracellular anion. It is one of four ions commonly measured in serum. The other three are sodium, potassium, and bicarbonate (Hco3). They are measured together because of important for regulation of acid-base and cation-anion balance. The four ions called as "serum electrolytes"

Function of Cl- 1- It is important for regulation acid-base and cation- anion balance. 2- It maintains electric neutrality of the fluid 3- It is involved in the formation of gastric hydrochloric acid. Cl- ingested in the diet is completely absorbed by the intestinal tract. Cl- ions are then filtered out by the glomerulus and passively reabsorbed, in conjunction with Na by proximal tubules. Excess Cl- is excreted in the urine and sweat. Excessive sweating stimulates asldosterone secretion, which acts on the sweat glands to conserve Na+ and Cl- .

Chloride shift: Electroneutrality is maintained by Cl- through the Cl- shift. In this process carbon dioxide (Co2) generated by cellular metabolism within the tissue diffuses out into both plasma and RBC. In RBC Co2 forms carbonic acid (H2Co3), which splits into H+ and HCo3 bicarbonate. The H+ would alter the pH if left unbound. But Hb readily accepts the H+ , forming deoxyhemoglobin (HHB). As the HCo3 con rises in RBC, if diffuses out into the plasma. In order to maintain electroneutrality (the same number of positively and negatively charged ions on each side of the RBC membrane).

Clinical significance: Decreases- Hypochloremia  1- Hypoventilation Inadequate removal of carbon dioxide from the blood by the lungs, regardless of cause, results in the accumulation of ionized (H2Co3) carbonic acid in the blood. The increase in the bicarbonate ion causes a reciprocal fall in serum chloride (it is excreted into the urine) Co2 + H2O ----------H2Co3------ H+ + HCo3

 2-Vomiting Vomiting over long periods results in the loss of chloride from the body and fall in serum chloride.  3-chronic diarrhea Loss of fluid over long periods will reduce the total body Cl- and produce hypochloremia.

4-Diabetic Ketoacidosis  Accumulation of organic acids (β-hydroxbutyric and acetoacetic acids) in serum. These are relatively strong acids, so, there is a displacement of both bicarbonate and Cl- ions. 5-Adrenal disease The adrenal gland produces hormones which control fluid and electrolytes are associate with low serum chloride con. 6- renal failure failing kidneys result in the accumulation of phosphate and sulfate anions which displace serum chloride. Hypoventilation

Magmesium The majority of Mg+2 is found in bone. It is next to potassium the most abundant intracellular cation. It act as activating ion for many enzymes involved in lipid, carbohydrates, and protein metabolism. Mean that, Mg+2 is an important cofactor for more than 300 enzymatic reactions, partically,those which require ATP.