Renal SAQ

2. Which renal mechanism,s does the body use to cope with decreasing pH?
The internal pH of the body is maintained at 7.35 to 7.45. Above a pH of 8,
alkalosis is present, whilst below a pH of 6, acidosis is present.
The pH is tightly regulated mainly by buffers such as protein and hydrogen
carbonate (H2CO3).
Causes of acidosis include severe diarrhea, hypoventilation and increased
consumption of acids.
Signs of acidosis are coma and hyperventilation.
If a decrease in pH occurs (acidosis), after a few days, the kidneys respond
in a way as to increase the pH towards a normal value again.
The kidneys cope with decreasing pH by secretion of H+ ions.
This occurs by secondary active transport in the proximal tubule and thick
ascending limb of the loop of Henle, and by primary active transport in the
distal tubule.
In the proximal tubule, H+ is secreted via Na/H pumps which reabsorb one
sodium ion for each hydrogen ion secreted. The gradient for the sodium is
achieved via the Na/K ATPase. The H+ secreted combines with tubular HCO3to form H2CO3 (H+ + HCO3- -> H2CO3) which is in turn reabsorbed into the
cells. In the cells, through the use of carbonic anhydrase, the H2CO3
is reverted back into HCO3- and H+. The HCO3- moves into the blood to buffer
more H+ whilst the H+ is again moved through the Na/H pump back into the
tubular fluid. This also occurs in the thick ascending loop of Henle.
In the distal tubule, H+ is secreted into the tubular fluid by H+ ATPase.
These pumps are found on the a-intercalated cells of the distal tubules.
The same principle of combination with HCO3-, rebasorption, break down and
re-secretion still applies.
Depletion of HCO3- generation of new HCO3If stores of HCO3- are depleted, phosphate takes over the role of HCO3- in
the tubular fluid, combining with H+ which is excreted as Na2HPo4.
Whilst this is happening, carbon dioxide enters the cells and react with
H20. CO2 + H20 -> H2CO3 <-> H+ + HCo3-. The H+ is again secreted to combine
with Na2HPO4 whilst the HCO3- is moved into blood to act as a buffer.
In this way, new HCO3- is formed.
Ammonia buffer - chronic acidosis
In the case of chronic acidosis, glutamine metabolism is stimulated in the
proximal tubule.
The ammonia buffering system works in two ways:
1. To generate new HCo32. Excreting H+ as NH4+
The generation of new HCO3- in the proximal tubule is very similar to the
phosphate buffer system. Secreted H+ reacts with NH3 to form NH4+ which is
secreted, whilst CO2 and H2O react to form HCO3- and H+.

In the proximal tubule, the NH4+ formed is secreted.

In the thick ascending limb, the NH4 is reabsorbed into the medullary
interstitium. Here, the N4+ dissociates into NH3 and H+ and the NH3
diffuses into the tubular fluid of the collecting duct.
H+ produced from CO2 reacting with H2O in the collecting duct will diffuse
into the tubular fluid, react with NH3 to form NH4 and is excreted.
From the information given above, it is clear that, whilst not the primary
defense against changes in pH, the kidneys still play an important role when
it comes to regulation of acid base balance of the body.
---------------------------------------------------------------------------3. Describe briefly the physiological mechanisms that maintain the sodium
balance and extracellular fluid volume
Sodium balance, otherwise known as osmoregulation, and extracellular fluid
volume (ECF), are two components of homeostasis which are important, with
detrimental effects if uncontrolled.
Hypernatriemia has several negative effects, including a cause of arrhythmias
and blood pressure changes, whilst hyponatremia is also potentially fatal.
ECF changes can cause oedema if high or dehydration if low.
Osmoregulation
Osmoregulation is the process by which the sodium level is regulated.
It occurs through the effect of two mechanisms:
1. ADH regulation
2. Thirst mechanism
ADH regulation - if the osmolality of the ECF is greater than 280 mm/l,
signals are sent to the ADH-synthesizing regions of the hypothalamus, which
stimulate the posterior pituitary gland, where ADH is stored, to secrete
ADH into the blood stream.
Doing so, the ADH will bind to V2 receptors of the basolateral cells of the
kidneys, stimulating a secondary response using G-proteins and cAMP which
results in the insertion of aquaporin channels into the basolateral membranes
of the cells of the distal tubule and collecting duct, thus making them
permeable to water reabsorption.
This then results in an increased reabsorption of water, which in turn causes
the excretion of a small volume of concentrated urine, whilst the osmolality
of the ECF decreases (due to dilution by more water).
If the osmolality of the ECF is less than 280 mm/l, ADH is not secreted, and
therefore the distal tubule and collecting duct are still impermeable to
water. A greater volume of dilute urine is excreted, with no change in the
ECF osmolality.
Thirst mechanism - People constantly lose water through their skin and whilst
breathing. The thirst mechanism is activated by an increase in sodium of the
ECF by 2-3%, or a fall in blood pressure by 10-15%.
The mechanism is evoked by the hypothalamus and/or by angiotensin II.
The effect is a dry mouth which results in a person drinking water (usually
the water ingested is near the exact amount to decrease osmolality to an
appropariate value), after which the cycle starts again.
ECF Volume regulation

Volume regulation is sensed as the effective tissue perfusion volume, and

regulation involves many receptors and effectors.
The factor being controlled is the effective circulating fluid volume.
The ECV varies directly with the extracellular fluid, and so primarily
depends on body sodium stores, as sodium is the main extracellular cation
which holds water in the extra cellular compartment.
So maintenance of ECV and regulation of sodium balance are directly and
closely related.
Atrial Natriuretic Peptide
Atrial natriuretic peptide (ANP) is a polypeptide hormone released by the
atria is response to an increase atrial pressure/volume.
It acts by binding to cell membrane receptors and activating the gyanylyl
cyclase pathway, which leads to formation of cGMP leading to 2 major
effects which contribute to volume regulation:
1. Increased water and sodium excretion, by directly closing sodium luminal
channels and suppressing the renin-angiontensin system, which reduces the
sodium reabsorption, and therefore increases both water and sodium excretion.
2. It acts as a direct vasodilator lowering the blood pressure and enhancing
GFR as it dilates the afferent arteriole more than the efferent one.
This also leads to an increase in sodium and water excretion.
Renin-Angiotensin-Aldosterone system