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SECTION VI
Cardiovascular Physiology
than the preceding normal contraction. This
postextrasystolic
potentiation
is independent of ventricular filling, since it occurs
in isolated cardiac muscle and is due to increased availability of
intracellular Ca
2+
. A sustained increment in contractility can be
produced therapeutically by delivering paired electrical stimuli to
the heart in such a way that the second stimulus is delivered
shortly after the refractory period of the first. It has also been
shown that myocardial contractility increases as the heart rate
increases, although this effect is relatively small.
Catecholamines exert their inotropic effect via an action on
cardiac
β
1
-adrenergic receptors and Gs, with resultant activation
of adenylyl cyclase and increased intracellular cyclic adenosineCLINICAL BOX 31–2
Shock
Circulatory shock comprises a collection of different entities
that share certain common features; however, the feature that
is common to all the entities is inadequate tissue perfusion
with a relatively or absolutely inadequate cardiac output. The
cardiac output may be inadequate because the amount of fluid
in the vascular system is inadequate to fill it
(hypovolemic
shock).
Alternatively, it may be inadequate in the relative sense
because the size of the vascular system is increased by vasodi-
lation even though the blood volume is normal (
distributive,
vasogenic,
or
low-resistance shock
). Shock may also be
caused by inadequate pumping action of the heart as a result
of myocardial abnormalities
(cardiogenic shock),
and by inad-
equate cardiac output as a result of obstruction of blood flow in
the lungs or heart
(obstructive shock).
Hypovolemic shock is also called “cold shock.” It is character-
ized by hypotension; a rapid, thready pulse; cold, pale, clammy
skin; intense thirst; rapid respiration; and restlessness or, alterna-
tively, torpor. None of these findings, however, are invariably
present. Hypovolemic shock is commonly subdivided into cate-
gories on the basis of cause. Of these, it is useful to consider the
effects of hemorrhage in some detail because of the multiple
compensatory reactions that come into play to defend extracel-
lular fluid (ECF) volume. Thus, the decline in blood volume pro-
duced by bleeding decreases venous return, and cardiac output
falls. The heart rate is increased, and with severe hemorrhage, a
fall in blood pressure always occurs. With moderate hemor-
rhage (5–15 mL/kg body weight), pulse pressure is reduced but
mean arterial pressure may be normal. The blood pressure
changes vary from individual to individual, even when exactly
the same amount of blood is lost. The skin is cool and pale and
may have a grayish tinge because of stasis in the capillaries and
a small amount of cyanosis. Inadequate perfusion of the tissues
leads to increased anaerobic glycolysis, with the production of
large amounts of lactic acid. In severe cases, the blood lactate
level rises from the normal value of about 1 mmol/L to 9 mmol/
L or more. The resulting
lactic acidosis
depresses the myocar-
dium, decreases peripheral vascular responsiveness to catechol-
amines, and may be severe enough to cause coma. When blood
volume is reduced and venous return is decreased, moreover,
stimulation of arterial baroreceptors is reduced, increasing
sympathetic output. Even if there is no drop in mean arterialpressure, the decrease in pulse pressure decreases the rate of
discharge in the arterial baroreceptors, and reflex tachycardia
and vasoconstriction result.
With more severe blood loss, tachycardia is replaced by
bradycardia; this occurs while shock is still reversible. With
even greater hemorrhage, the heart rate rises again. The
bradycardia is presumably due to unmasking a vagally medi-
ated depressor reflex, and the response may have evolved as a
mechanism for stopping further blood loss. Vasoconstriction is
generalized, sparing only the vessels of the brain and heart. A
widespread reflex venoconstriction also helps maintain the fill-
ing pressure of the heart. In the kidneys, both afferent and ef-
ferent arterioles are constricted, but the efferent vessels are
constricted to a greater degree. The glomerular filtration rate is
depressed, but renal plasma flow is decreased to a greater ex-
tent, so that the filtration fraction increases. Na
+
retention is
marked, and the nitrogenous products of metabolism are re-
tained in the blood (
azotemia
or
uremia
). If the hypotension is
prolonged, renal tubular damage may be severe
(acute renal
failure).
After a moderate hemorrhage, the circulating plasma
volume is restored in 12 to 72 h. Preformed albumin also enters
rapidly from extravascular stores, but most of the tissue fluids
that are mobilized are protein-free. After the initial influx of
preformed albumin, the rest of the plasma protein losses are
replaced, presumably by hepatic synthesis, over a period of 3
to 4 d. Erythropoietin appears in the circulation, and the reticu-
locyte count increases, reaching a peak in 10 d. The red cell
mass is restored to normal in 4 to 8 wk.
The treatment of shock is aimed at correcting the cause and
helping the physiologic compensatory mechanisms to restore
an adequate level of tissue perfusion. If the primary cause of the
shock is blood loss, the treatment should include early and rapid
transfusion of adequate amounts of compatible whole blood. In
shock due to burns and other conditions in which there is
hemoconcentration, plasma is the treatment of choice to re-
store the fundamental defect, the loss of plasma. Concentrated
human serum albumin and other hypertonic solutions expand
the blood volume by drawing fluid out of the interstitial spaces.
They are valuable in emergency treatment but have the disad-
vantage of further dehydrating the tissues of an already dehy-
drated patient.