Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

II. Kidney Morphology and Function
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reviews in Hoenderop and Bindels (2005) and Hoenderop
et al. (2005) . This final reabsorption is mainly under the
hormonal control of PTH.
● Magnesium: Non-protein-bound magnesium is filtered
by the glomerulus. Only about 25% are reabsorbed
in the proximal tubule. Most reabsorption occurs in the
ascending branch of the loop of Henle (50% to 60%)
( Rosol and Capen, 1996 ).
c . Water
Most water ( 75%) is reabsorbed passively in the proximal
tubule along with ions and small hydrophilic molecules,
so that the fluid entering the descending branch
is isotonic. Water is reabsorbed in the descending branch
of Henle’s loop as a result of the corticopapillary osmolar
gradient, whereas the ascending branch is impermeable to
water. Final reabsorption occurs in the collecting tubule,
mainly under the hormonal control of the antidiuretic hormone
(ADH). This hypothalamic nonapeptide is secreted
by the posthypophysis when osmolality increases and during
hypovolemia or decreased blood pressure. Receptors in
the collecting tubule cells trigger the AMPc-dependent synthesis
and shuttling of aquaporins, mainly the AQP2 water
channel, into the apical and basolateral membrane, thereby
permitting water reabsorption and the final adjustment
of urine concentration. See the review in Nielsen et al.
(2002). The final urine concentration is usually much
greater than that of the glomerular filtrate ( Fig. 16-4 ).
d . Acid-Base Regulation
The main organs involved in acid-base regulation are the
kidneys and lungs. The lungs modulate the elimination of
CO 2 and the kidneys the elimination of protons and generation
of bicarbonate ions.
The carbonic acid (H 2 CO 3 )-bicarbonate (HCO 3 ) buffer
system is the most efficient extracellular buffer system.
It is based on the low dissociation of carbonic acid (pKa
6.1) at the pH of the extracellular/intravascular compartment
and the fact that it is an open system eliminating
CO 2 in the lungs. Its efficiency is enhanced by the action
of carbonic anhydrase, which accelerates the hydration of
carbonic anhydride (CO 2 ) into carbonic acid. High concentrations
of carbonic anhydrase occur in many tissues
including the kidney tubule. The relationship between CO 2 ,
H 2 CO 3 , and HCO 3 is expressed in the following equation:
H O CO ⇆ H CO ⇆ HCO H
2 2 2 3
Bicarbonate ions filtered by the glomerulus are mainly reabsorbed
in the proximal tubule ( 80%) as CO 2 , which is lipophilic
and able to diffuse across the membrane. Within the
cell, CO 2 is hydrated by carbonic anhydrase into carbonic
acid, which dissociates into bicarbonate ions and protons.
The secretion of protons into the tubule lumen ensures the
3
FIGURE 16-4 Water reabsorption in the kidney tubule (values are
osmolalities). The corticomedullary osmotic gradient results from reabsorption
of sodium and chloride without concomitant reabsorption of
water in the ascending limb of the loop of Henle and from urea reabsorption
in the medullary part of the collecting ducts. Owing to water
permeability of the descending limb of the loop of Henle plasma isoosmotic
urine flowing from the proximal tubule is first concentrated in the
descending branch of the loop of Henle, then is diluted by escape of NaCl
and water retention in the ascending branch, and finally is concentrated
along the collecting ducts. Reproduced with permission of the publisher
from Finco (1995b) .
conservation of bicarbonate and its transfer to the plasma.
This occurs principally in the distal tubule, where protons
are excreted and buffered in urine with filtered organic
anions, phosphate, and ammonia generated from glutamine
in the tubule cells by the action of glutaminase and glutamate
dehydrogenase. This process is enhanced during acidosis,
when distal tubule and collecting tubule cells excrete
protons against a concentration gradient by the action of an
H -ATPase in the basolateral membrane.
e . Endocrine Functions
Two major hormones, erythropoietin (EPO) and 1 α ,
25-dihydroxycholecalciferol (calcitriol), are synthesized by
the kidneys and released into the blood.
EPO is a cytokine that regulates erythrocyte production
synthesized in the peritubular cells in response to hypoxia.
Minor amounts are also produced in the liver, mainly in the
newborn. EPO binds to receptors of bone marrow progenitor
cells and acts synergistically with other growth factors to proliferate
and mature the erythroid progenitor cells. In advanced
chronic renal disease, the synthesis of EPO decreases and is
insufficient to meet the demands for new red cell production,
resulting in anemia. See the review in Fisher (2003).
Calcitriol is a secoBsteroid hormone derived from vitamin
D 3 . It is produced in the proximal tubule cells by the