Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 90 Water And Electrolyte Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
1. Convoluted portion of proximal tubule
2. Pars recta: cont reabsorptn of NaCl and secretion of organic acid
3. Thin descendinglimb
4. Thin ascending limb
5. Thick ascending limb
6. Distal conv tubule: Active sodium reabsorption
7. Cortical collecting tubule: Active sodium reabsorption
8. Collecting duct: allows equilibration of water with the
hyperosmotic interstitium when ADH is present
INHIBITORS OF NA+-CL- SYMPORT (THIAZIDE AND THIAZIDELIKE DIURETICS)
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
before reaching the DCT.
Some thiazide diuretics also are weak inhibitors of carbonic anhydrase,
an effect that increases HCO3 - and phosphate excretion
and probably accounts for their weak proximal tubular effects.
Like inhibitors of Na+-K+-2Cl- symport,
inhibitors of Na+-Cl- symport increase the excretion of K+ and
titratable acid by the same mechanisms discussed for loop diuresis.
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+
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
Na+ channels.
Other mechanisms contributing to enhanced K+ and H+ excretion
include flow-dependent enhancement of ion secretion by the collecting duct,
nonosmotic vasopressin release,
and activation of the renin-angiotensin-aldosterone axis
INHIBITORS OF RENAL EPITHELIAL NA+ CHANNELS (K+-SPARING DIURETICS)
Carbonic anhydrase inhibitors, loop diuretics, and
thiazide diuretics increase the delivery of Na+ to the late distal tubule and
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
of the luminal membrane and thereby enhances the lumen-negative VT,
which facilitates K+ excretion.
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,
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
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.
Epithelial cells in the late distal tubule and collecting duct contain
cytosolic MRs
that have a high affinity for aldosterone
AIP, aldosterone-induced proteins; ALDO, aldosterone;
MR, mineralocorticoid receptor; CH, ion channel
1, activation of membrane-bound Na+ channels
2, redistribution of Na+ channels from cytosol to membrane;
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;
6, de novo synthesis of Na+,K+-ATPase;
7, changes in permeability of tight junctions;
8, increased mitochondrial production of ATP
Mechanism of action of aldosterone
Epithelial cells in the late distal tubule and collecting duct contain cytosolic MRs
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)
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+
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
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
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.
Electrolyte and Water Composition of Body Fluid Compartments
Components
Plasma
Interstitial fluid
Intracellular fluid
Volume, H2O (TBW 3.5 L
10.5 L
28 L
= 42 L)
Na+
142
145
12
K+
4
4
156
Ca+2
2.4
2-3
2.3
Mg2+
2
1-2
26
Trace elements
1
-
-
Total cations
155
Cl-
103
114
4
HCO-
27
31
12
Protein-
16
-
55
Organic acids-
5
HPO2 -
2
SO2 -
1
Total anions
154
Reference interval of Sodium
:
136-145 mmol/L (Adult)
128-148 mmol/L (New born at 48 h)
Approx 127 mmol/L (From Umbilical cord)
Urinary sodium excretion = 120-240 mmol/day with large diurnal variation
At night = 20% of the peak
Hyponatremia typically manifests clinically as
(1) nausea,
(2) generalize weakness, and
(3) mental confusion.
<120 mmol/L: mental confusion
<110 mmol/L : Ocular palsy
90-105 mmol/L: Severe mental impairment
Algorithm for the differential diagnosis of hyponatremia.
Hypernatremia Plasma sodium > 150 mmol/L
Symptoms are primarily neurologic
(because of neuronal cell loss of H2O into the ECF)
1.Tremors
2.Irritability
3.Ataxia
4.Confusion
5.coma
Hypernatremia
HYPOKALEMIA
Reference interval of K+:
1.Muscle weakness
Serum=3.5-5.0 mmol/L (Adult)
2.Irritability
3.Paralysis
Plasma= 3.4-4.8 mmol/L (Adult)
4.Tachycardia
5.Cardiac conduction defect
3.7-5.9 mmol/L ( Newborn)
6.Flattened T wave
CSF= 70% that of plasma
7.Cardiac arrest
Hypokalemia
Hypokalemia (continued)
Metabolic Alkalosis
HYPERKALEMIA
1. Mental confusion
2. Weakness
3. Tingling
4. Flaccid paralysis of the extremities
5. Weakness of the respiratory muscles
6. Bradicardia
7. Conduction defects
8. Peripheral vascular collapse : Prolonged severe hyperkalemia >7 mmol/L
9. Cardiac arrest
Hyperkalemia
This post was last modified on 05 April 2022