Biological function of inorganic elements

1. Biological function of inorganic elements Dr. Sherin Bakhashab

2. Body Fluids Components • Intracellular fluid (ICF) compartment: fluid found in the cells (cytoplasm, nucleoplasm) comprises 60% of all body fluids. • Extracellular fluid (ECF) compartment: all fluids found outside the cells, comprises 40% of all body fluids. It is distributed between plasma and interstitial fluid.

3. Composition of Body Fluids • Water is the main component of all body fluids making up 45-75% of the total body weight. • Solutes are broadly classified into: • Electrolytes are inorganic salts, all acids and bases, and some proteins • Nonelectrolytes – examples include glucose, lipids, creatinine, and urea • Electrolytes have greater osmotic power than nonelectrolytes • Water moves according to osmotic gradients

4. Electrolyte Composition of Body Fluids • Extracellular Fluids • ECFs are similar except for the high protein content of plasma • Sodium (Na+) is the major cation                    • Chloride (Cl-)is the major anion • Intracellular Fluids • Have low sodium and chloride • Potassium (K+) is the chief cation • Phosphate (PO4-) is the chief anion

5. Extracellular and Intracellular Fluids Sodium and potassium concentrations in extra- and intracellular fluids are nearly opposites

6. Sodium, Potassium and Chloride • Sodium is the principle cation in the ECF. • Potassium is the principle cation in ICF. • Chloride is the main anion in the ECF. • Sources and requirements: • Na and Cl are obtained from NaCl of food (cheese, bread, whole grain). • K is found in large quantities in beef, chicken, some fruits and potatoes. • The daily intake of NaCl is about 10-15g and 98% is eliminated by the faeces. • The amount of K in diet is 2-4 g.

7. Sodium, Potassium and Chloride • Distribution: The total amount of Na in the body is about 4000 mmoles. • 50% are present in ECF (2000 mmoles) • 3% are present in ICF (140 mmoles) • 47% are present in bone (1900 mmoles) The total amount of K in the body is about 4300 mmoles. • 98% are present in ICF (4200 mmoles) • 1% is present in ECF (50 mmoles) • 1% is present in bones (50 mmoles)

8. Blood levels • Most Na and Cl are present in the blood plasma, while most of the K is present in the red blood cells.

9. Functions • Production of gastric HCl by the parietal cells: The process of acid secretion begins with the hydrolysis of water to form one H+ and OH- in the cytoplasm of parietal cells. Secretion of H+ into the lumen is an active process driven by H+ /K+ ATPase. The pump exchanges H+ for K+ . Then Cl- ions diffuse through open chloride channel. * CA = Carbonic anhydrase

10. Functions • b) Maintenance of normal acid-base balance (Chloride shift) • During normal metabolic activity, acids are continually being formed, which should be neutralized and excreted through lungs and kidneys to maintain the acid-base equilibrium. Plasma

11. Functions

12. Functions • The red cell membrane is permeable to HCO3- but impermeable to K+ . • HCO3- diffuse outside the RBCs in exchange for chloride ions (Cl-) which shifts into the cell in order to maintain electrical ions neutrality across the erythrocyte membrane. • Cl- ions are neutrilized by K+ while sodium bicarbonate is formed in the plasma. • This process occurs when CO2 tensions is increased and this explains the higher chloride content in venous RBCs than arterial RBCs. • In arteries, where CO2 tension is reduced, the reverse occurs, i.e., the Cl- leaves the cells and enters the plasma.

13. Active transport system for Na+ and K+ • Pumping Na+ ions out and K+ in against strong concentration gradients called Na+ - K+ pump. • It requires ATP as source of energy • Active transport in cells controls the concentration gradient, muscle contraction, nerve impulse, and drives the active transport of sugars and amino acids. • ATP drives the transfer of Na+ and K+ across the membrane by the following mechanism:

15. Important features of the pump • For each ATP hydrolysed, 3 Na+ are removed from the cell and 2K+ enters the cell. • Na+ triggers phosphorylation, whereas K+ triggers dephosphorylation.

16. Transport of sugars and amino acid by Na+ flow • Transport of sugar (glucose) into the cell is coupled by simultaneous entry of Na+ .

17. Transport of sugars and amino acid by Na+ flow • Na+ and glucose bind to a specific transport protein and enter together by symport carriers. • Na+ enters the cell are pumped out by Na+ - K+ pump. • The rate of glucose transport depends on the Na+ concentration gradient across the membrane. • Symports driven by Na+ are widely used by the animal cells to transport amino acids. • This symport system is present in the plasma membrane of intestinal and kidney cells. • Na+ is a driving force in antiport that releases Ca++ from variety of cells. • Most symports and antiports are driven by Na+ gradients generated by Na+ - K+ pump.

18. Na and Cl absorption • Na+ and Cl- are present in the luminal content of small intestine. • Na+ moves into brush border of the intestinal cell by a carrier (glucose) mediated mechanism. • Na+ is then released by Na+ - K+-ATPase present in the lateral and basal cell membrane. • Cl- follow Na+ into the cell to maintain the ionic equilibrium.

19. K absorption • Most of K is absorbed in small intestine (77%) . • K+ absorption in small intestinal epithelium is passive process, as it passes between the cells and tight junctions. • Absorption is driven according to electrochemical gradient, i.e, following ingestion of K+ the concentration in lumen will be greater than that in ECF.

20. Na, K and Cl excretion • Na and Cl are eliminated mainly in the urine and to a lesser extent in the perspiration. • K is normally eliminated in the urine. • Reabsorption of electrolytes, mainly Na, by the distal tubular cells (kidney) is under the control of adrenal cortical hormones aldosterone and deoxycorticosterone.

21. Action of Aldosterone on Na transport • When the concentration of electrolytes and osmotic pressure of plasma fall below certain level, the adrenal cortex secretes hormones which increase the reabsorption of Na salts, therefore restoring electrolytes to plasma and increasing osmotic pressure. • When plasma electrolytes and osmotic pressure rise above normal, the adrenal cortex secretes less hormones, permitting the excretion of more Na salts and lowering osmotic pressure.

22. Disorders of Sodium metabolism • A) Sodium deficiency (hyponatremia) • Low Na concentration in blood < 136 mmol/L. • External Na loss: such as due to vomiting, diarrhoea, sweating, skin diseases. In such cases, dehydration accompanied with electrolytes loss, therefore the patient should receive sufficient amount of water and salts. • Primary renal Na loss: • Diuretic phase of acute renal failure (eg. Post-renal transplantation): normally this stage is short-lived (lasting few days) but it may occasionally be prolonged. • Chronic renal failure with salt restriction

23. Disorders of Sodium metabolism 3. Secondary Na renal loss are essentially induced by hormone or diuretic as in: • Addison’s disease due to decreased aldosterone. • Congenital adrenal hyperplasia due to impaired mineralocorticoid synthesis (deficiency of some enzymes) • Diuretic abuse

24. Symptoms and treatment • Symptoms are nonspecific and can include: • Mental changes • Headache • Nausea and vomiting • Tiredness • Muscle spasms and seizures • Severe hyponatremia can lead to coma and can be fatal. • Treatment of hyponatremia involves intravenous fluid and electrolyte replacement

25. Disorders of Sodium metabolism • B) Sodium excess (hypernatremia) High Na concentration in blood > 145 mmol/L. • With oedema: • Pregnancy: sodium retention in order to expand the maternal plasma volume and interstitial fluid space to provide the foetus with sodium.

26. Disorders of Sodium metabolism • Without oedema: • Acute Na loading: rare, caused by inappropriate Na administration to highly dependant individuals. • Renal Na retention due to: • Excess mineralocorticoids (aldosterone) • Primary hyperaldosteronism (eg. Adenoma: is a benign tumour of epithelial tissue with glandular origin) • Secondary hyperaldosteronism eg. Rennin-secreting tumour.

27. Disorders of Potassium Balance • Hypokalemia refers to a decrease in plasma potassium level below 3.5 mmol/L. • Causes of hypokalemia: • Pseudohypokalemia -Extreme leukocytosis • Decreased K intake • Increased K losses -Nonrenal: Skin: by diaphoresis (excessive sweating, can be a symptom of various conditions) Gastrointestinal: diarrhea and vomiting -Renal

28. Clinical manifestations • Cardiovascular: -Hypertension -Arrhythmias • Neuromuscular: 1.Smooth muscle: 2.Skeletal muscle: -Weakness -Paralysis • Endocrine: -Glucose intolerance (↓insulin release and sensitivity) • Renal: - Decrease blood flow

29. Hyperkalemia • Hyperkalemia refers to an increase in plasma levels of potassium in excess of 5.0 mmol/L. • Causes of hyperkalemia: • Excessive intake: rare as sole cause • Impaired renal K+ excretion -Endogenous or exogenous K+ -Drugs that impair K+ excretion

30. Clinical manifestations • Cardiovascular abnormalities • Neuromuscular -Weakness -Paralysis • Renal/electrolyte -Decreased ammonia production -Metabolic acidosis: is a condition that occurs when the body produces excessive quantities of acid or when the kidneys are not removing enough acid from the body. In hyperkalemia, acidosis can develop by the transcellular shift of K+ when intracellular K+ is exchanged for extracellular H+.

31. References • http://www.austincc.edu/apreview/EmphasisItems/Electrolytefluidbalance.html#bodyfluids • Bioinorganic chemistry: A short course, by Rosette M. Roat-Malone.