Download MBBS Biochemistry PPT 90 Water And Electrolyte Lecture Notes

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3. Thin descendinglimb

4. Thin ascending limb

5. Thick ascending limb

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6. Distal conv tubule: Active sodium reabsorption

7. Cortical collecting tubule: Active sodium reabsorption

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8. Collecting duct: allows equilibration of water with the

hyperosmotic interstitium when ADH is present
INHIBITORS OF NA+-CL- SYMPORT (THIAZIDE AND THIAZIDELIKE DIURETICS)

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inhibitors of Na+-Cl- symport increase Na+ and Cl- excretion. However, thiazides are

only moderately efficacious (i.e., maximum excretion of filtered load of Na+ is

only 5%) because approximately 90% of the filtered Na+ load is reabsorbed

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before reaching the DCT.

Some thiazide diuretics also are weak inhibitors of carbonic anhydrase,

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an effect that increases HCO3 - and phosphate excretion

and probably accounts for their weak proximal tubular effects.

Like inhibitors of Na+-K+-2Cl- symport,

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inhibitors of Na+-Cl- symport increase the excretion of K+ and

titratable acid by the same mechanisms discussed for loop diuresis.

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INHIBITORS OF NA+-K+-2CL- SYMPORT (LOOP DIURETICS, HIGH-CEILING DIURETICS

All inhibitors of Na+-K+-2Cl- symport increase the urinary excretion of K+ and

titratable acid. This effect is due in part to increased delivery of Na+

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to the distal tubule. The mechanism by which increased distal delivery of Na+

enhances excretion of K+ and H+ is discussed in the section on inhibitors of

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Na+ channels.

Other mechanisms contributing to enhanced K+ and H+ excretion

include flow-dependent enhancement of ion secretion by the collecting duct,

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nonosmotic vasopressin release,

and activation of the renin-angiotensin-aldosterone axis
INHIBITORS OF RENAL EPITHELIAL NA+ CHANNELS (K+-SPARING DIURETICS)

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Carbonic anhydrase inhibitors, loop diuretics, and

thiazide diuretics increase the delivery of Na+ to the late distal tubule and

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collecting duct, a situation that often is associated with increased K+ and

H+ excretion. It is likely that the elevation in luminal Na+ concentration in

the distal nephron induced by such diuretics augments depolarization

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of the luminal membrane and thereby enhances the lumen-negative VT,

which facilitates K+ excretion.

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increased distal delivery of Na+ is not the only mechanism by which diuretics

increase K+ and H+ excretion. Activation of the renin-angiotensin-aldosterone

axis by diuretics also contributes to diuretic-induced K+ and H+ excretion,

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As the sodium rushes back into the cell the positive sodium ions raise

the charge inside the cell from negative to positive. Once the interior

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of the cell becomes positively charged,

depolarization of the cell is complete

Effects of aldosterone on late distal tubule and collecting duct and diuretic mechanism of aldosterone antagonists.

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Epithelial cells in the late distal tubule and collecting duct contain

cytosolic MRs

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that have a high affinity for aldosterone

AIP, aldosterone-induced proteins; ALDO, aldosterone;

MR, mineralocorticoid receptor; CH, ion channel

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1, activation of membrane-bound Na+ channels

2, redistribution of Na+ channels from cytosol to membrane;

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3, de novo synthesis of Na+ channels; 4, activation of membrane-

bound Na+, K+-ATPase;

5, redistribution of Na+,K+-ATPase from cytosol to membrane;

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6, de novo synthesis of Na+,K+-ATPase;

7, changes in permeability of tight junctions;

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8, increased mitochondrial production of ATP
Mechanism of action of aldosterone

Epithelial cells in the late distal tubule and collecting duct contain cytosolic MRs

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that have a high affinity for aldosterone

Aldosterone enters the epithelial cell from the basolateral membrane and binds to MRs; the MR-aldosterone

complex translocates to the nucleus, where it binds to specific sequences of DNA (hormone-responsive elements)

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and thereby regulates the expression of multiple gene products called aldosterone-induced proteins (AIPs). Figure

illustrates some of the proposed effects of AIPs, including activation of "silent" Na+ channels and "silent" Na+

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pumps that pre-exist in the cell membrane, alterations in the cycling of Na+ channels and Na+ pumps between the

cytosol and cell membrane such that more channels and pumps are located in the membrane, increased

expression of Na+ channels and Na+ pumps, changes in permeability of the tight junctions, and increased activity

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of enzymes in the mitochondria that are involved in ATP production. The precise mechanisms by which AIPs alter

transport are incompletely understood. However, the net effect of AIPs is to increase Na+ conductance of the

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luminal membrane and sodium pump activity of the basolateral membrane. Consequently, transepithelial NaCl

transport is enhanced, and the lumen-negative transepithelial voltage is increased. The latter effect increases the

driving force for secretion of K+ and H+ into the tubular lumen.

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Electrolyte and Water Composition of Body Fluid Compartments

Components

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Plasma

Interstitial fluid

Intracellular fluid

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Volume, H2O (TBW 3.5 L

10.5 L

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28 L

= 42 L)
Na+

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142

145

12

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K+

4

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4

156

Ca+2

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2.4

2-3

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2.3

Mg2+

2

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1-2

26

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Trace elements

1

-

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-

Total cations

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155

Cl-

103

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114

4

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HCO-

27

31

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12

Protein-

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16

-

55

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Organic acids-

5

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HPO2 -

2

SO2 -

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1

Total anions

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154
Reference interval of Sodium

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:

136-145 mmol/L (Adult)

128-148 mmol/L (New born at 48 h)

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Approx 127 mmol/L (From Umbilical cord)

Urinary sodium excretion = 120-240 mmol/day with large diurnal variation

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At night = 20% of the peak

Hyponatremia typically manifests clinically as

(1) nausea,

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(2) generalize weakness, and

(3) mental confusion.

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<120 mmol/L: mental confusion

<110 mmol/L : Ocular palsy

90-105 mmol/L: Severe mental impairment

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Algorithm for the differential diagnosis of hyponatremia.
Hypernatremia Plasma sodium > 150 mmol/L

Symptoms are primarily neurologic

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(because of neuronal cell loss of H2O into the ECF)

1.Tremors

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2.Irritability

3.Ataxia

4.Confusion

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5.coma


Hypernatremia

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HYPOKALEMIA

Reference interval of K+:

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1.Muscle weakness

Serum=3.5-5.0 mmol/L (Adult)

2.Irritability

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3.Paralysis

Plasma= 3.4-4.8 mmol/L (Adult)

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4.Tachycardia



5.Cardiac conduction defect

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3.7-5.9 mmol/L ( Newborn)

6.Flattened T wave

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CSF= 70% that of plasma

7.Cardiac arrest
Hypokalemia

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Hypokalemia (continued)

Metabolic Alkalosis
HYPERKALEMIA

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1. Mental confusion

2. Weakness

3. Tingling

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4. Flaccid paralysis of the extremities

5. Weakness of the respiratory muscles

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6. Bradicardia

7. Conduction defects

8. Peripheral vascular collapse : Prolonged severe hyperkalemia >7 mmol/L

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9. Cardiac arrest

Hyperkalemia