Major Electrolytes & Their Homeostasis Part-1

Major Electrolytes & Their Homeostasis according to course curriculum of Medical Biochemistry for MBBS

1. MAJOR ELECTROLYTES & THEIR HOMEOSTASIS DR. FARHANA ATIA Associate Professor Department of Biochemistry Nilphamari Medical College, Nilphamari

2. ELECTROLYTE DISTRIBUTION ELECTROLYTES ECF ICF Na⁺ 140 mmol/L 10 mmol/L K⁺ 4 mmol/L 140 mmol/L Ca⁺⁺ 2.5 mmol/L 0.1 μ mol/L Mg⁺⁺ 1.5 mmol/L 30 mmol/L Cl ⁻ 100 mmol/L 4 mmol/L HCO₃⁻ 27 mmol/L 10 mmol/L PO₄⁻⁻ 2 mmol/L 60 mmol/L Glucose 5.5 mmol/L 0-1 mmol/L Protein 2 gm/dL 16 gm/dL Harper’s Illustrated Biochemistry 31 st edition p-460

3. Functions of electrolytes Body water homeostasis Maintenance of pH & acid base balance Regulation of heart and muscle function Role in electron transfer reaction Serving as cofactor for enzymes

4. OSMOLALITY & OSMOLARITY Serum osmolality : A laboratory measurement of number of osmoles per kilogram of solvent. It is approximated by serum osmolarity Serum osmolarity : The number of osmoles per liter of solution Equation for serum osmolarity 2(Na⁺+ K ⁺)+ Glucose + Urea (mmol/L) Normal serum osmolarity: 280- 300 mmol/L

5. OSMOLAR GAP Osmolar gap: Measured osmolality - Calculated osmolarity Normal osmolar gap: 10 mmol/L If the osmolar gap is >10 mmol/L, this indicates the presence of additional solutes (osmotically active particles) DM (↑ glucose) ↑ Ethanol Mannitol Ethylene glycol

6. SODIUM (Na) Na content of body: 3600- 4200 mmol Distribution: In ECF: 90% , In ICF: 10% Intake : 100 - 200 mmol/day (table salt, fruit, diet) Output: 100 - 200 mmol/day Route of excretion Urine 90% Feces 5% Sweat 5%

7. Maintenance of Na balance

8. Maintenance of Na balance Hormonal regulation Aldosterone : Stimulate Na reabsorption in DCT & CD in exchange of K⁺/H ⁺ Renin-angiotensin system Stimulate aldosterone secretion  Na retention Ang II ↑ Na reabsorption in PCT ANP - atrial natriuretic peptide: Secreted from right atrial wall Natriuresis by reducing NaCl reabsorption from DCT & CD

9. Renin-angiotensin-aldosterone system

10. Maintenance of Na balance Kidney: Depends on dietary intake & physiological need T L of Na: 25000 mmol/day (>99% reabsorbed, <1% excreted) Reabsorption of Na PCT : 60-70% reabsorption. Always accompanied by relevant anion (Cl⁻/HCO₃⁻) ALLH : 20-25% reabsorption. Na ⁺- 2Cl⁻- K⁺ symport mechanism DCT : 5% reabsorption. Na⁺ -Cl⁻ symport CD : 5% reabsorption. Na⁺- K⁺/H⁺ exchange

11. Maintenance of Na balance Selective transport mechanism Na pump maintain low ICF Na & high ECF Na ECV ECV ↑  ↓ Na reabsorption & ↑ excretion Thirst may regulate Na intake Sympathetic stimulation - causes salt & water retention Environmental condition- excessive heat, vigorous exercise increase loss of Na

12. Excess NaCl ↑ Na in plasma ↓ ↑ ECV ↓ ↑ RBF ↓ (+) Baroreceptor (-) Renin ↓ (+) ANP (+) VMC ↓ ↓ Ang II ↓ ↓ Sympathetic outflow ↓ ↓ Aldosterone ↑ Na excretion ↑ GFR ↓ ↓ Na reabsorption ↑ Na & water excretion

13. Inadequate NaCl ↓ NaCl ↓ ↓ plasma [Na⁺] ↓ ↓ ECF volume ↓ (+) JGA ↓ ↑ Na reabsorption ↓ ↑ Ang II ↓ ↓ Na excretion ↓ ↑ Aldosterone secretion Normalization of plasma [Na⁺]

14. HYPONATRAEMIA Na <135 mmol/L in ECF Plasma [Na] depends on the amount of both Na & water So, hyponatremia does not necessarily imply Na depletion Assessment of fluid status is the key to diagnosis

15. Isotonic Hyponatremia Plasma osmolarity – Normal Na concentration - ↓ Causes Hyperproteinemia Hyperlipidemia

16. Hypertonic Hyponatremia Plasma osmolarity – Increased Na concentration - ↓ Actually no reduction of total body Na Dilutional drop of [Na] due to presence of osmotically active particle in plasma which causes water shift from ICF to ECF Causes Hyperglycemia Uremia ↑ Mannitol, sorbitol, glycerol in blood Corrected Na level: Measured Na(mmol/L)+Glucose/4

17. Hypotonic hyponatremia i ) Hypovolemic (concentrated urine) ii) Euvolemic iii) Hypervolemic Extrarenal (Lose Na & H ₂ O other than via kidney) SIADH CCF Dehydration Diarrhea Vomiting Hypothyroidism CLD Post operative NS Renal (Lose Na & H ₂ O via kidney) ACTH deficiency Advance RF Renal failure Diuretic excess ACE inhibitor Mineralocorticoid deficiency( Aldosterone )

18. Hypernatremia Na >145 mmol/L Causes: Water loss in excess of Na loss Primary hyperaldosteronism Secondary hyperaldosteronism i ) Reduce water intake ii) Increase loss from skin Coma Fever Inability to swallow Hyperthyroidism Nausea Hot environment Water unavailable Voluntary reduction

19. Hypernatremia causes iii) Increase loss from respiratory tract Hyperventilation High altitude Fever iv) Increase loss in urine Diabetes insipidus Diabetes mellitus Chronic nephritis Drugs: Lithium Hypercalcemia

20. Potassium Total body K⁺: 3000-3500 mmol (45 mmol/Kg body wt ) ICF: 98% (140- 150 mmol/L) ECF: 2% ( 3.5-5 mmol/L ) Whatever the amount of ICF K ⁺ severe hypo & hyperkalemia are dangerous Intake & output: 100-200 mmol/d Excretion: Urine: 60-80 mmol/d Feces: 10 mmol/day Sweat

21. Obligatory K ⁺ loss It is the amount of K⁺ loss that must be excrete. Not less than 5-10 mmol/d It may be up to 10 times of normal ie . 600-800 mmol /d Maintenance of K⁺ balance depends on regulation of urinary K⁺ excretion

22. Renal handling of K⁺ Tubular load: 700-800 mmol/d Reabsorption: 98% PCT: 70% ALLH: 28% Secretion: In DCT, CD Urinary K is not the filtered K, it’s the secreted amount Mechanism: Na-K/H exchange mechanism Excretion: 80 mmol/day which equals the daily intake of K

23. Factors regulating K⁺ excretion Rate of Na reabsorption in DCT & CD: ↑ Na reabsorption  ↑ K⁺ secretion(antiport) Aldosterone activity Aldosterone activity ↑  ↑ K⁺ loss Acid base status of body Acidosis  Excess H ⁺ excretion & ↓ K⁺ excretion hyperkalemia Alkalosis ↑ K⁺ excretion  hypokalemia

24. Factors regulating K⁺ excretion Body K⁺ status: ↑ cellular K⁺  ↑excretion Rate of flow in distal nephron ↑ K flow ↑ excretion Presence of poorly reabsorbed anion (PO₄, Ketone) & non absorbed anion in filtrate ↑ K⁺ excretion Dietary load of K Excretion of K⁺ is proportional to intake

25. Regulation of K⁺ balance Renal regulation Transmembrane K⁺ flux It is the shift of K⁺ into the cell (influx) & from the cell (efflux) Renal regulation requires some time. But body cannot tolerate small fluctuation of ECF K So for safety purpose excess K of ECF is temporarily hidden inside the cell very quickly & vice versa

26. K⁺ influx Causes of K⁺ influx Insulin Beta agonist Alkalosis Aldosterone Thyroxin Barium intoxication

27. K⁺ efflux Beta blocker Alpha agonist Metabolic acidosis Increased osmotic pressure of ECF Insulin deficiency (diabetic ketoacidosis) Burn Hemolysis Infection Internal bleeding Vigorous exercise K⁺ sparing diuretics

28. Variation of K⁺ Hypokalemia < 3.5 mmol/L Severe <2.5 mmol/L 0.5 mmol/L variation in a day or within 24 hours may cause hypo/hyperkalemia Hyperkalemia >5 mmol/L Severe >7.5 mmol/L

29. Causes of Hypokalemia K⁺ influx Increase insulin secretion(post-prandial) Alkalosis Stimulation of β adrenergic receptor Barium intoxication Hyperthyroidism K⁺ loss Renal cause Extra renal cause

30. Causes of Potassium loss Renal Increase aldosterone effect Primary hyperaldosteronism Secondary hyperaldosteronism Renovascular hypertension Cushing syndrome Ectopic ACTH producing tumor Steroid Therapy Increase urinary output Diuretics Salt loosing nephropathy Renal Hypomagnesemia Renal tubular acidosis Nephritis Fanconi’s Syndrome Extra Renal Vomiting Diarrhea Laxative abuse Zollinger Ellison syndrome Villous adenoma

31. Clinical Features of Hypokalemia Muscular weakness Fatigue Muscle cramp Constipation / Paralytic ileus Flaccid paralysis Hyporeflexia Hypercapnia Tetany ECG change

32. ECG Findings of Hypokalemia Decrease amplitude & broadening of T wave Prominent U wave Premature ventricular contraction & depressed ST segment Prolongation of PR interval Depends on level of hypokalemia

33. Hyperkalemia Decrease Potassium excretion Renal failure Nephritis Renal transplantation SLE Sickle cell disease Amyloidosis Heparin Potassium sparing diuretics Potassium efflux- all causes of K efflux

34. Hyperkalemia Excessive intake of Potassium Hyperkalemia due to faulty lab technique Delayed serum separation from cell Repeated tourniquet Specimen drawn from an arm with K infusion

35. Clinical feature of hyperkalemia Interfere with normal muscular function Effect on heart (Rapidly fatal) Muscle weakness Flaccid paralysis Abdominal distension Loss of tendon jerk Paralytic ileus Constipation then diarrhea Tall peak T wave Prolong QRS complex Ventricular arrythmia

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