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 μmol/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 31st 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
•Selective transport
Hormonal regulation
Kidney
ECV/effective circulatory volume
Thirst
Sympathetic stimulation
Environmental condition

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
• TL 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
Hypertonic
Isotonic
Hypotonic
Hypervolemic
Euvolemic
Hypovolemic

15. Isotonic Hyponatremia
• Plasma osmolarity – Normal
• Na concentration - ↓
• Causes
1. Hyperproteinemia
2. 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
1. Hyperglycemia
2. Uremia
3. ↑ 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 & H₂O other
than via kidney)
SIADH CCF
Dehydration
Diarrhea
Vomiting
Hypothyroidism CLD
Post operative NS
Renal (Lose Na & H₂O 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
1. Primary hyperaldosteronism
2. 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
1. K⁺ influx
– Increase insulin secretion(post-prandial)
– Alkalosis
– Stimulation of β adrenergic receptor
– Barium intoxication
– Hyperthyroidism
2. 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

36. Thank You