Reabsorption and Secretion Along Different Parts of the Nephron
Proximal Tubular ReabsorptionNormally, about 65 % of the filtered load of sodium , water and a slightly lower percentage of chloride are reabsorbed. These percentages can be ↑↑ or ↓↓in different physiologic conditions.
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The proximal tubule epithelial cells are
highly metabolichave large numbers of mitochondria (for active transport
have an extensive brush border on the luminal (apical) side of the membrane
extensive labyrinth of intercellular and basal channels which provides extensive membrane surface area of the epithelium for rapid transport of sodium ions and other substances.
have protein carrier molecules that transport a large fraction of the sodium ions across the luminal membrane counter-transport mechanisms
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The proximal tubule secretes:
* organic acids and bases such as bile salts, oxalate, urate, and catecholamines.
* harmful drugs or toxins (penicillin and salicylates).
*secretion of hydrogen ions (an important step in the removal of bicarbonate ions from the tubule (by combining H+ with the HCO3- to form H2CO3, which then dissociates into H2O and CO2).
*para-aminohippuric acid (PAH).
PAH :is secreted so rapidly that the average person can clear about 90 % of the PAH from the plasma flowing through the kidneys and excrete it in the urine.
The rate of PAH clearance can be used to estimate the renal plasma flow.
Loop of Henle
The loop of Henle consists of three functionally distinct segments:
1-thin descending segment
2-thin ascending segment,
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The thin descending and thin ascending segments have thin epithelial membranes with no brush borders, few mitochondria, and minimal levels of metabolic activity.
The thin descending segment is highly permeable to water and moderately permeable to most solutes, including urea and sodium.
About 20 % of the filtered water is reabsorbed in the loop of Henle, and almost all of this occurs in the thin descending limb.
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The ascending limb, including both the thin and the thick portions, is virtually impermeable to water, this is important for concentrating the urine.
About 25 % of the filtered loads of Na+,Cl- and k+ are reabsorbed in the loop of Henle, mostly in the thick ascending limb.
The thin segment of the ascending limb has a much lower reabsorptive capacity than the thick segment.
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The thick ascending loop of Henle is virtually impermeable to water.( most of the water remains in the tubule so the fluid in the ascending limb becomes very dilute as it flows toward the distal tubule,& this is important in allowing the kidneys to dilute or concentrate the urine under different conditions.
The sodium-potassium ATPase pump in the basolateral cell membrane maintains a low intracellular Na +and a negative electrical potential in the cell. The thick ascending limb also has a sodium hydrogen counter-transport mechanism in its luminal cell membrane that mediates sodium reabsorption and hydrogen secretion in this segment.
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Distal Tubule
Consist of :
*Early distal tubule) forms part of the juxtaglomerular complex that provides feedback control of GFR and blood flow in this same nephron).
*Late distal tubule(reabsorbs most of the ions, including sodium,potassium, and chloride, but is virtually impermeable to water and urea).
Approximately 5 % of the filtered load of sodium chloride is reabsorbed in the early distal tubule.
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Sodium and chloride are transported from the tubular lumen into the cell by a co-transporter (inhibited by thiazide diuretics) .Sodium is pumped out of the cell by sodium-potassium ATPase and chloride diffuses into the interstitial fluid via chloride channels.
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Late Distal Tubule and Cortical Collecting Tubule
Two cell types:
1.The principal cells reabsorb sodium and water from the lumen and secrete potassium ions into the lumen (depend on the activity of a sodium- potassium ATPase pump .
2. The intercalated cells reabsorb potassium ions and secrete hydrogen ions this mediated by a hydrogen-ATPase. Hydrogen is generated in this cell by the action of carbonic anhydrase on water and carbon dioxide to form carbonic acid.
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Sodium enters the cell through special channels and is transported out of the cell by the sodium-potassium ATPase pump.
-Aldosterone antagonists compete with aldosterone.
-Sodium channel blockers directly inhibit the entry of sodium into the sodium channels
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The functional characteristics of the late distal tubule and cortical collecting tubule:
*almost completely impermeable to urea
*Both the late distal tubule and the cortical collecting tubule segments reabsorb sodium controlled by (aldosterone)
*the intercalated cells play a key role in acid-base regulation of the body fluids ( through secretion of hydrogen ions by an active hydrogen-ATPase mechanism)
*The permeability of the late distal tubule and cortical collecting duct to water is controlled by the concentration of ADH With high levels of ADH, these tubular segments are permeable to water and vice versa.
Medullary Collecting Duct
medullary collecting ducts reabsorb less than 10 % of the filtered water and sodium. the epithelial cells of the collecting ducts are cuboidal in shape with smooth surfaces, few mitochondria.
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Special characteristics of medullary collecting Segment:
Its permeability to water is controlled by the level of ADH.
permeable to urea
capable of secreting hydrogen ions against a large concentration gradient
plays a key role in regulating acid-base balance.
Regulation of Tubular Reabsorption
Glomerulotubular Balance: the intrinsic ability of the tubules to increase their reabsorption rate in response to increased tubular load (increased tubular inflow).
For e.g.:, if GFR is increased from 125 ml/min to 150 ml/min, the absolute rate of proximal tubular reabsorption also increases from about 81 ml/min (65 % of GFR) to about 97.5 ml/min (65 % of GFR). Glomerulotubular balance acts as a second line of defense to buffer the effects of spontaneous changes in GFR on urine output( the 1st line is renal autoregulatory mechanisms).
Peritubular Capillary and Renal Interstitial Fluid Physical Forces
Hydrostatic and colloid osmotic forces govern the rate of reabsorption across the peritubular capillaries.
As the glomerular filtrate passes through the renal tubules, more than 99 % of the water and most of the solutes are normally reabsorbed. The normal rate of peritubular capillary reabsorption is about 124 ml/min.
The net reabsorptive pressure
The net reabsorptive pressure is normally about 10 mmHg, causing fluid and solutes to be reabsorbed into the peritubular capillaries as they are transported across the renal tubular cells. SHAPE \* MERGEFORMAT
The other factor that contributes to the high rate of fluid reabsorption in the peritubular capillaries is a large filtration coefficient (Kf) ,The reabsorption rate is normally about 124ml/min and net reabsorption pressure is10mmHg Kf normally is about 12.4ml/min/mm Hg.
The peritubular capillary hydrostatic pressure is influenced by:
-the arterial pressure and- resistances of the afferent and efferent arterioles.
The major determinant of peritubularcapillary reabsorption:
(1) Increases in arterial pressure tend to raise peritubular capillary hydrostatic pressure and decrease reabsorption rate.
(2) Increase in resistance of either the afferent or the efferent arterioles reduces peritubular capillary hydrostatic pressure and tends to increase reabsorption rate.
The colloid osmotic pressure of peritubular capillaries is determined by
the systemic plasma colloid osmotic pressure; increasing the plasma protein concentration of systemic blood tends to raise peritubular capillary colloid osmotic pressure, (increasing reabsorption);
the filtration fraction; the higher the filtration fraction, the greater the fraction of plasma filtered through the glomerulus and, consequently, the more concentrated the protein becomes in the plasma that remains behind.
Filtration fraction(Ff)= GFR/renal plasma flow
Increased Ff can occur as a result of increased GFR or decreased renal plasma flow.
Some renal vasoconstrictors, (angiotensin II), increase peritubular capillary reabsorption by decreasing renal plasma flow and increasing (Ff ).
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Proximal tubular and peritubular capillary reabsorption under normal conditions and during decreased peritubular capillary reabsorption caused by either increasing peritubular capillary hydrostatic pressure (Pc) or decreasing peritubular capillary colloid osmotic pressure (pc).
Reduced peritubular capillary reabsorption,, decreases the net reabsorption of solutes and water by increasing the amounts of solutes and water that leak back into the tubular lumen through the tight junctions of the tubular epithelial cells, especially in the proximal tubule.
Factors affect the rate of tubular reabsorption of fluid
Osmotic diuresis
2. Plasma colloid osmotic pressure
3. Sympathetic stimulation
4. Arterial pressure (without autoregulation of the GFR in diseased kidney)
5. Hormonal control
Hormonal control
1- ADH (acute and chronic effect) ( decrease urine output
2.Aldosterone increases Na reabsorption and increases K & H ions secretion (distal and collecting tubules) ( decrease urine output.
3.Angiotensin II
--stimulates aldosterone secretion with consequent increase Na reabsorption and increases K & H ions secretion ( decrease urine output.
-- stimulates directly (proximal tubules) Na-K ATPase pump at the basolateral membrane of the tubular cell and Na-H exchange at the luminal side of the tubular cell with consequent increase in Na reabsorption and K & H ions secretion ( decrease urine output.
--constricts the efferent arterioles ( decrease urine output( decreases the blood flow into the peritubular capillaries ( the capillary pressure is decreased ( increasing tubular reabsorption.
-- ( decreases the blood flow through glomeruli ( very high proportion of plasma fluid to filter through the glomerular membrane into tubules ( increases plasma proteins in the blood leaving the glomeruli ( increases colloid osmotic pressure of the peritubular capillary ( increases tubular reabsorption.
-- constricts Mesangial cells ( reduces the capillary filtration coefficient ( decreases GFR ( decrease urine output
4.Atrial natriuretic peptide inhibits the reabsorption of Na and water by the renal tubules in the collecting ducts ( increase urine output.
5. Parathyroid hormone increases the reabsorption of Ca and Mg ions from the ascending limb of loop of Henle and distal tubule. inhibits the reabsorption of phosphate from the proximal tubule).
Effect of Arterial Pressure on Urine Output
Pressure natriuresis and pressure diuresis:
Small increases in arterial pressure → marked increases in urinary excretion of sodium and water,but because of autoregulatory mechanisms increasing the arterial pressure between 75-160 mm Hg usually has only a small effect on renal blood flow and GFR.
1st effect
The slight increase in GFR that does occur contributes in part to the effect of increased arterial pressure on urine output.
When GFR autoregulation is impaired ,e.g., kidney disease, increases in arterial pressure cause much larger increases in GFR.
2nd effect of increased renal arterial pressure that raises urine output is that it decreases the percentage of the filtered load of sodium and water that is reabsorbed by the tubules slight increase in peritubular capillary hydrostatic pressure, especially in the vasa recta & increase in the renal interstitial fluid hydrostatic pressure.this enhances back leak of sodium into the tubular lumen, reducing the net reabsorption of sodium and water and further increasing the rate of urine output when renal arterial pressure rises.
3rd rd factor that contributes to the pressure natriuresis is reduced angiotensin II formation.
Angiotensin II
*increases sodium reabsorption by the tubules; it also
*stimulates aldosterone secretion, which further increases sodium reabsorption.
Therefore, decreased angiotensin II formation contributes to the decreased tubular sodium reabsorption that occurs when arterial pressure is increased.