Beruflich Dokumente
Kultur Dokumente
passive diffusion due to the slight positive charge of the tubular lumen relative to the interstitial fluid.
The remaining 50% of calcium reabsorption in the thick ascending limb occurs through the transcellular
pathway, a process that is stimulated by PTH.
In the distal tubule, calcium reabsorption
occurs almost entirely by active transport through
the cell membrane. The mechanism for this active
transport is similar to that in the proximal tubule
and thick ascending limb and involves diffusion
across the luminal membrane through calcium
channels and exit across the basolateral
membrane by a calcium-ATPase pump, as well as
a sodium-calcium counter transport mechanism
4. Therefore, phosphate normally begins to spill into the urine when its concentration in the
extracellular fluid rises above a threshold of about 0.8 mM/L, which gives a tubular load of
phosphate of about 0.1 mM/min, assuming a GFR of 125 ml/min.
The proximal tubule normally reabsorbs 75-80 percent of the filtered phosphate. The distal tubule
reabsorbs about 10 percent of the filtered load, and only very small amounts are reabsorbed in the loop
of Henle, collecting tubules, and collecting ducts. Approximately 10 percent of the filtered phosphate is
excreted in the urine.
In the proximal tubule, phosphate reabsorption occurs mainly through the transcellular pathway.
Phosphate enters the cell from the lumen by a sodium-phosphate co-transporter and exits the cell
across the basolateral membrane by a process that is not well understood but may involve a counter
transport mechanism in which phosphate is exchanged for an anion
PTH can play a significant role in regulating phosphate concentration through two effects:
1. PTH promotes bone resorption, thereby dumping large amounts of phosphate ions into the
extracellular fluid from the bone salts
2. PTH decreases the transport maximum for phosphate by the renal tubules, so a greater
proportion of the tubular phosphate is lost in the urine
Thus, whenever plasma PTH is increased, tubular phosphate reabsorption is decreased and more
phosphate is excreted
Sodium Excretion is controlled by Altering Glomerular Filtration or Tubular Sodium Reabsorption Rates
Excretion = Glomerular filtration Tubular reabsorption
GFR normally is about 180 L/day, tubular reabsorption is 178.5 L/day, and urine excretion is 1.5 L/day.
Thus, small changes in GFR or tubular reabsorption potentially can cause large changes in renal
excretion. Similarly, small changes in tubular reabsorption, in the absence of compensatory
adjustments of GFR, would also lead to dramatic changes in urine volume and sodium excretion.
Even with disturbances that alter GFR or tubular reabsorption, changes in urinary excretion are
minimized by various buffering mechanisms. For example, if the kidneys become greatly vasodilated
and GFR increases (as can occur with certain drugs or high fever), this raises sodium chloride delivery
to the tubules, which in turn leads to at least two intrarenal compensations:
1. Increased tubular reabsorption of much of the extra sodium chloride filtered, called
glomerulotubular balance<
2. Macula densa feedback, in which increased sodium chloride delivery to the distal tubule causes
afferent arteriolar constriction and return of GFR toward normal
Because neither of these two mechanisms operates perfectly to restore distal sodium chloride delivery
all the way back to normal, changes in either GFR or tubular reabsorption can lead to significant
changes in urine sodium and water excretion. When this happens, other feedback mechanisms come
into play, such as changes in blood pressure and changes in various hormones
During changes in sodium and fluid intake, this feedback mechanism helps to maintain fluid balance
and to minimize changes in blood volume, extracellular fluid volume, and arterial pressure as follows:
1. An increase in fluid intake (assuming that sodium accompanies the fluid intake) above the level
of urine output causes a temporary accumulation of fluid in the body.
2. As long as fluid intake exceeds urine output, fluid accumulates in the blood and interstitial
spaces, causing parallel increases in blood volume and extracellular fluid volume. As discussed
later, the actual increases in these variables are usually small because of the effectiveness of
this feedback.
3. An increase in blood volume raises mean circulatory filling pressure.
4. An increase in mean circulatory filling pressure raises the pressure gradient for venous return.
5. An increased pressure gradient for venous return elevates cardiac output.
6. An increased cardiac output raises arterial pressure.
7. An increased arterial pressure increases urine output by way of pressure diuresis. The steepness
of the normal pressure natriuresis relation indicates that only a slight increase in blood pressure
is required to raise urinary excretion several fold.
8. The increased fluid excretion balances the increased intake, and further accumulation of fluid is
prevented.
Precision of Blood Volume and Extracellular Fluid Volume Regulation
One can see why the blood volume remains almost exactly constant despite extreme changes in daily
fluid intake. The reason for this is the following:
1. A slight change in blood volume causes a marked change in cardiac output,
2. A slight change in cardiac output causes a large change in blood pressure
3. A slight change in blood pressure causes a large change in urine output
These factors work together to provide effective feedback control of blood volume
Reference:
Guyton Textbook of Medical Physiology 12th
Edition