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

V. Physiology of Acid-Base Balance
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This highly sensitive system responds rapidly to small
changes in osmolality, and as a result, plasma osmolality is
normally maintained within a relatively narrow range.
C . Renin-Angiotensin
The renin-angiotensin system plays an important role in the
maintenance of effective circulating fluid volume. Renin is
a proteolytic enzyme produced by special juxtaglomerular
cells of the glomerular afferent arteriole. Renin is released
in response to reduced renal perfusion produced by hypotension,
volume depletion, or increased sympathetic activity.
Renin converts the circulating globulin angiotensinogen
to angiotensin I, which is subsequently converted by an
enzyme in the lung and vascular endothelial cells to the biologically
active form, angiotensin II. Angiotensin II exerts a
variety of systemic effects that tend to correct hypovolemia
and hypotension. Angiotensin II increases renal retention
of sodium and water by enhancing secretion of aldosterone
from the adrenal cortex as well as having direct effects on
the renal tubule. Angiotensin II exerts hemodynamic effects,
which tend to increase blood pressure by inducing arteriolar
vasoconstriction.
D . Aldosterone
Aldosterone plays a central role in the maintenance of
effective circulating fluid volume and potassium balance
largely through its effects on renal resorption of sodium in
exchange for potassium and hydrogen ion. Aldosterone is
produced in the adrenal cortex and exerts its effects on sensitive
cells, such as the renal collecting tubules, by interacting
with specific cytoplasmic receptors. The aldosterone
receptor complexes subsequently enhance RNA-mediated
production of specific proteins, which actually mediate the
physiological effects of the hormone. There is evidence for
aldosterone-mediated effects on gastrointestinal sodium
and potassium absorption as well as effects on sweat glands
to alter the electrolyte composition of sweat in response to
sodium depletion ( Michell, 1974 ). Aldosterone secretion is
enhanced by the renin-angiotensin system in response to
changes in effective circulating fluid volume.
E . Atrial Natriuretic Factor
Atrial natriuretic factor (ANF), also known as atrial natriuretic
peptide (ANP), exists as a group of diverse peptide
hormones produced in the heart and released into the circulation
in response to processes that increase central venous
pressure and thereby stretch the atrial wall ( Inagami, 1994 ).
The actions of ANF that tend to reduce cardiac output
and systemic blood pressure are mediated by transmembrane
receptors, which result in the production of cyclic
guanidine monophosphate generated by guanylyl cyclase
( Inagami, 1994 ). ANF results in natriuresis and diuresis by
the kidneys. ANF also causes vasodilatation and reduces
fluid volume by acting directly on vascular smooth muscle
and inhibiting the release of aldosterone from the adrenal
cortex and norepinephrine from peripheral adrenergic
neurons. Additionally, ANF has been found in the brain,
and centrally medicated effects on fluid volume regulation
may be important. Elevated plasma ANF has been noted
in humans with a variety of diseases ranging from congestive
heart failure to obstructive lung disease to chronic
renal failure. However, the physiological importance of
ANF in these disease processes is not completely resolved.
In humans, Bartter’s syndrome and Gordon’s syndrome
are thought to be due to an excess or deficiency of ANF,
respectively ( Christensen, 1993 ). In horses, the elevation
of plasma ANF has been associated with treadmill exercise
( McKeever et al. , 1991 ).
V . PHYSIOLOGY OF ACID-BASE BALANCE
The hydrogen ion concentration of the ECF is maintained
within remarkably narrow limits and is normally approximately
40 nmol/l. This concentration is roughly one-millionth
the concentration of other common electrolytes. Even at these
extremely low concentrations, hydrogen ions have profound
effects on metabolic events largely through interaction with
cellular proteins. These interactions alter protein configuration
and thus alter protein function. Most enzymatic reactions
have a narrowly defined range of pH optimum, and changes
in hydrogen ion concentration have direct effects on the rates
of reaction and, thus, many basic biological processes.
A . Definition of pH
Although the hydrogen ion concentration can be expressed
in nmol/l a more useful expression is that of pH. The pH of
a solution is equal to the negative logarithm of the hydrogen
ion concentration.
pH log [H
]
(17-2)
It is important to remember that the pH varies inversely
with hydrogen ion concentration. When hydrogen concentration
in the blood increases, pH decreases, and the animal
develops an acidosis. When the hydrogen ion concentration
in the blood decreases, the pH rises, and the animal develops
an alkalosis. The traditional view of acid-base balance
involves the following:
1. Extracellular and intracellular buffering
2. Regulation of the rate of alveolar ventilation to control
carbon dioxide concentration
3. Regulation of renal hydrogen excretion
B . Buffers
A buffer system consists of a weakly dissociated acid and
the salt of that acid. The body buffers are able to take up