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Clinical Biochemistry
SIMS-305
Dr. Ali Raza
Senior Lecturer
Centre for Human Genetics and Molecular Medicine (CHGMM),
Sindh Institute of Medical Sciences (SIMS), SIUT.
1
Group. II: SODIUM
SODIUM
• Chief Electrolyte
• Large conc. in extracellular fluid (ECF)
• Mainly associated with Chloride as
• NaCl
• NaHCO3
 Absorption of Sodium:
• Sodium Pump (Na+-K+ ATPase)
• Situated in plasma membrane of
Intestinal
Renal cells
SODIUM PUMP (Na+-K+ ATPase)
• Na-pump is an enzyme,
• Requires Mg++ and ATP
• Uses the energy (ATP) to transport
three Na+ outside
two K+ inside the cell membrane
SODIUM PUMP
• Intracellular Na+ conc. is 10 mM
• Extracellular Na+ conc. is 150 mM
• Na-pump maintain both magnitudes and direction of
transmembrane concentration gradients of those ions
Forms of Sodium Pump
 Na+-K+ ATPase exists in two forms:
• E1
• E2
Sodium Pump Mechanism
E1 form E2 form E form
Three sodium ions and two K ions are transported across cell
membrane
Sodium Pump Mechanism
The E1 form:
• Presents its ion binding and phosphate binding sites on the
cytoplasmic surface of the membrane.
• Three sodium ions from cytoplasm bind with the ion binding
sites of E1.
• This leads to the phosphorylation of aspartate residue of E1
with the help of ATP and Mg++.
• Results in conformational change and E1 becomes E2.
Sodium Pump Mechanism
E2 exposes
• Ion binding and phosphate binding sites, lowers the
affinity of the ATPase for Na+ and releases it into the ECF.
• K+ ions from ECF bind to the respective ion binding site,
lowers the affinity of E2 for phosphate.
• This dephosphorylation changes the conformation of E2 to
E1 again and lowers its affinity for K+ ions.
• This leads to release of the K+ ions from ATPase into the
cell.
Sodium Pump Mechanism
Sodium - FUNCTIONS
Fluid balance
 Blood viscosity
Acid-base balance
Role in resting membrane potential
 Role in Action Potential
 Neuromuscular excitability
Sodium - FUNCTIONS
Fluid balance:
• maintains osmotic pressure of extracellular fluids (ECF)
• helps in retaining water in ECF.
 Neuromuscular excitability:
• Na+ is also involved in neuromuscular irritability
Acid-base balance: Na+-H+ exchange in renal tubule to
acidify urine.
 Maintenance of viscosity of blood:
• Salts of Na with globulins are soluble
• Na+ and K+ maintaining the degree of hydration of the
plasma proteins.
Sodium- FUNCTIONS
 Role in resting membrane potential:
• Plasma membrane has a poor Na+ permeability and passive
Na+ inflow through it.
• Na-pump keeps Na+ conc. far higher outside than inside.
separation of charges of the membrane, Polarisation
Role in Action Potential:
• A local depolarisation of nerve or muscle fibre is observed
in stimulation.
• This rapidly increases its permeability to Na+ causing
considerable transmembrane influx of Na+ down its inward
conc. gradient.
Sodium - CLINICAL ASPECT
Clinical conditions are of two major types
I. Hypernatraemia
II. Hyponatraemia
CLINICAL ASPECT
Hypernatraemia :
• infers that the extracellular sodium is excessive
relative to water.
• A high plasma sodium conc. does not necessarily
mean that the total body sodium content is
increased
• Decrease in body water
• Increase in body sodium
Specific conditions in which hypernatraemia occurs
 Simple Dehydration
 Diabetes Insipidus
 Osmotic Loading
 Excess Sodium
Hypernatraemia
Simple dehydration:
• Result of excessive sweating with inadequate
or no water replacement.
Diabetes Insipidus:
• Condition characterized by large amounts of dilute
urine and increased thirst.
• Water loss due to lack of antidiuretic hormone (ADH)
• kidney cells are unable to respond to the hormone.
Hypernatraemia
Osmotic loading:
• Due to large excretory quantities of very soluble
substances (glucose, urea,)
• Osmotic effect of these substances on the urine causes
excretion of large amounts of water.
• Relatively little sodium is excreted. So the plasma level rises.
• ill patients on high protein diet, urea is formed which is
then excreted in very large amounts along with large
volumes of water.
Hypernatraemia
Excess sodium
• 0.9 % NaCl is administered intravenously –154mEq/L.
• Excessive use of isotonic saline particularly in
children leads to hypernatraemia.
• Administration of NaHCO3 in treatment of acidosis
may cause Hypernatraemia
II. Hyponatraemia
 Diuretic medication
 Excessive sweating
 Kidney diseases
 Congestive heart failure
 Gastrointestinal loss
Diuretic medication:
• Many diuretic medications act by promoting excretion of
Na by kidney.
• To lower the total body sodium and extracellular water
• E.g: this objective is desired, viz. congestive heart failure,
chronic kidney disease and hypertension.
• Reduced total body sodium is achieved but extracellular
volume reaches critical dimension
• there is a counter effort to retain water which then dilutes
the sodium and hyponatraemia results.
II. Hyponatraemia
 Excessive sweating:
• Loss of fluids of high Na+ and Cl–
(like sweating)
• but replaced by salt deficient fluids
• water by mouth
• Glucose solution by IV.
Kidney diseases:
• Kidneys, glomerulus is the one in which blood is
filtered and Na is reabsorbed by the renal tubules.
• Due to kidney dysfunction, Na+ is not reabsorbed and
is thus excreted in the urine.
• There is also a progressive failure to excrete water.
Congestive heart failure:
• Hyponatraemia is common in
heart failure for two reasons:
a) Diuretics administration
b) Congestive heart failure : cause low Na+ conc.
• It is because the low cardiac output is sensed
incorrectly by the brain as low blood volume,
• Calling increased secretion of ADH.
 Gastrointestinal loss
• Diarrhoea:
• Result in reduced sodium/chloride levels
in plasma and extracellular fluid.

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Sodium -minerals and trace elements

  • 1. Clinical Biochemistry SIMS-305 Dr. Ali Raza Senior Lecturer Centre for Human Genetics and Molecular Medicine (CHGMM), Sindh Institute of Medical Sciences (SIMS), SIUT. 1
  • 3. SODIUM • Chief Electrolyte • Large conc. in extracellular fluid (ECF) • Mainly associated with Chloride as • NaCl • NaHCO3  Absorption of Sodium: • Sodium Pump (Na+-K+ ATPase) • Situated in plasma membrane of Intestinal Renal cells
  • 4. SODIUM PUMP (Na+-K+ ATPase) • Na-pump is an enzyme, • Requires Mg++ and ATP • Uses the energy (ATP) to transport three Na+ outside two K+ inside the cell membrane
  • 5. SODIUM PUMP • Intracellular Na+ conc. is 10 mM • Extracellular Na+ conc. is 150 mM • Na-pump maintain both magnitudes and direction of transmembrane concentration gradients of those ions
  • 6. Forms of Sodium Pump  Na+-K+ ATPase exists in two forms: • E1 • E2
  • 7. Sodium Pump Mechanism E1 form E2 form E form Three sodium ions and two K ions are transported across cell membrane
  • 8. Sodium Pump Mechanism The E1 form: • Presents its ion binding and phosphate binding sites on the cytoplasmic surface of the membrane. • Three sodium ions from cytoplasm bind with the ion binding sites of E1. • This leads to the phosphorylation of aspartate residue of E1 with the help of ATP and Mg++. • Results in conformational change and E1 becomes E2.
  • 9. Sodium Pump Mechanism E2 exposes • Ion binding and phosphate binding sites, lowers the affinity of the ATPase for Na+ and releases it into the ECF. • K+ ions from ECF bind to the respective ion binding site, lowers the affinity of E2 for phosphate. • This dephosphorylation changes the conformation of E2 to E1 again and lowers its affinity for K+ ions. • This leads to release of the K+ ions from ATPase into the cell.
  • 11. Sodium - FUNCTIONS Fluid balance  Blood viscosity Acid-base balance Role in resting membrane potential  Role in Action Potential  Neuromuscular excitability
  • 12. Sodium - FUNCTIONS Fluid balance: • maintains osmotic pressure of extracellular fluids (ECF) • helps in retaining water in ECF.  Neuromuscular excitability: • Na+ is also involved in neuromuscular irritability Acid-base balance: Na+-H+ exchange in renal tubule to acidify urine.  Maintenance of viscosity of blood: • Salts of Na with globulins are soluble • Na+ and K+ maintaining the degree of hydration of the plasma proteins.
  • 13. Sodium- FUNCTIONS  Role in resting membrane potential: • Plasma membrane has a poor Na+ permeability and passive Na+ inflow through it. • Na-pump keeps Na+ conc. far higher outside than inside. separation of charges of the membrane, Polarisation Role in Action Potential: • A local depolarisation of nerve or muscle fibre is observed in stimulation. • This rapidly increases its permeability to Na+ causing considerable transmembrane influx of Na+ down its inward conc. gradient.
  • 14. Sodium - CLINICAL ASPECT Clinical conditions are of two major types I. Hypernatraemia II. Hyponatraemia
  • 15. CLINICAL ASPECT Hypernatraemia : • infers that the extracellular sodium is excessive relative to water. • A high plasma sodium conc. does not necessarily mean that the total body sodium content is increased • Decrease in body water • Increase in body sodium
  • 16. Specific conditions in which hypernatraemia occurs  Simple Dehydration  Diabetes Insipidus  Osmotic Loading  Excess Sodium
  • 17. Hypernatraemia Simple dehydration: • Result of excessive sweating with inadequate or no water replacement. Diabetes Insipidus: • Condition characterized by large amounts of dilute urine and increased thirst. • Water loss due to lack of antidiuretic hormone (ADH) • kidney cells are unable to respond to the hormone.
  • 18. Hypernatraemia Osmotic loading: • Due to large excretory quantities of very soluble substances (glucose, urea,) • Osmotic effect of these substances on the urine causes excretion of large amounts of water. • Relatively little sodium is excreted. So the plasma level rises. • ill patients on high protein diet, urea is formed which is then excreted in very large amounts along with large volumes of water.
  • 19. Hypernatraemia Excess sodium • 0.9 % NaCl is administered intravenously –154mEq/L. • Excessive use of isotonic saline particularly in children leads to hypernatraemia. • Administration of NaHCO3 in treatment of acidosis may cause Hypernatraemia
  • 20. II. Hyponatraemia  Diuretic medication  Excessive sweating  Kidney diseases  Congestive heart failure  Gastrointestinal loss
  • 21. Diuretic medication: • Many diuretic medications act by promoting excretion of Na by kidney. • To lower the total body sodium and extracellular water • E.g: this objective is desired, viz. congestive heart failure, chronic kidney disease and hypertension. • Reduced total body sodium is achieved but extracellular volume reaches critical dimension • there is a counter effort to retain water which then dilutes the sodium and hyponatraemia results.
  • 22. II. Hyponatraemia  Excessive sweating: • Loss of fluids of high Na+ and Cl– (like sweating) • but replaced by salt deficient fluids • water by mouth • Glucose solution by IV.
  • 23. Kidney diseases: • Kidneys, glomerulus is the one in which blood is filtered and Na is reabsorbed by the renal tubules. • Due to kidney dysfunction, Na+ is not reabsorbed and is thus excreted in the urine. • There is also a progressive failure to excrete water.
  • 24. Congestive heart failure: • Hyponatraemia is common in heart failure for two reasons: a) Diuretics administration b) Congestive heart failure : cause low Na+ conc. • It is because the low cardiac output is sensed incorrectly by the brain as low blood volume, • Calling increased secretion of ADH.
  • 25.  Gastrointestinal loss • Diarrhoea: • Result in reduced sodium/chloride levels in plasma and extracellular fluid.

Editor's Notes

  • #4:  pump is a device that moves fluids (liquids or gases), or sometimes slurries, by mechanical action.
  • #5: In cells
  • #6: By active transports Na into extracellular fluid.
  • #9: Three sodium ions from cytoplasm bind with the ion binding sites of E1. This leads to the phosphorylation of aspartate residue of E1 with the help of ATP and Mg++.
  • #18: Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. Complications may include dehydration or seizures.
  • #25: cardiac output is usually expressed in liters/minute.