486 Chapter 14
response occurs in diving mammals and, to a lesser degree,
in Japanese pearl divers during prolonged submersion. These
responses help deliver blood to the two organs that have the
highest requirements for aerobic metabolism.
Vasoconstriction in organs other than the brain and heart
raises total peripheral resistance, which helps (along with the
reflex increase in cardiac rate) to compensate for the drop in
blood pressure due to low blood volume. Constriction of arteri-
oles also decreases capillary blood flow and capillary filtration
pressure. As a result, less filtrate is formed. At the same time,
the osmotic return of fluid to the capillaries is either unchanged
or increased (during dehydration). The blood volume is thus
raised at the expense of tissue fluid volume. Blood volume is
also conserved by decreased urine production, which occurs
as a result of vasoconstriction in the kidneys and the water-
conserving effects of ADH and aldosterone, which are secreted
in increased amounts during shock.
Septic Shock
Septic shock refers to a dangerously low blood pressure
(hypotension) that may result from sepsis, or infection. This
can occur through the action of a bacterial lipopolysaccharide
called endotoxin. The mortality associated with septic shock
is presently very high, estimated at 50% to 70%. According
to recent information, endotoxin activates the enzyme nitric
oxide synthase within macrophages—cells that play an impor-
tant role in the immune response (chapter 15). As previously
discussed, nitric oxide synthase produces nitric oxide, which
promotes vasodilation and, as a result, a fall in blood pressure.
Septic shock has recently been treated effectively with drugs
that inhibit the production of nitric oxide.
Other Causes of Circulatory Shock
A rapid fall in blood pressure occurs in anaphylactic shock
as a result of a severe allergic reaction (usually to bee stings
or penicillin). This results from the widespread release of his-
tamine, which causes vasodilation and thus decreases total
peripheral resistance. A rapid fall in blood pressure also occurs
in neurogenic shock, in which sympathetic tone is decreased,
usually because of upper spinal cord damage or spinal anesthe-
sia. Cardiogenic shock results from cardiac failure, as defined
by a cardiac output inadequate to maintain tissue perfusion.
This commonly results from infarction that causes the loss
of a significant proportion of the myocardium. Cardiogenic
shock may also result from severe cardiac arrythmias or valve
damage.
Congestive Heart Failure
Cardiac failure occurs when the cardiac output is insufficient to
maintain the blood flow required by the body. This may be due
to heart disease—resulting from myocardial infarction or con-
genital defects—or to hypertension, which increases the after-
load of the heart. The most common causes of left ventricular
heart failure are myocardial infarction, aortic valve stenosis,
and incompetence of the aortic and bicuspid (mitral) valves.
This can become a vicious cycle, where a myocardial infarc-
tion causes heart failure that results in heart muscle remodel-
ing, which can in turn promote dangerous arrythmias. Failure
of the right ventricle is usually caused by prior failure of the
left ventricle.
Heart failure can also result from disturbance in the electro-
lyte concentrations of the blood. Excessive plasma K^1 concen-
tration decreases the resting membrane potential of myocardial
cells, and low blood Ca^2 1 reduces excitation-contraction cou-
pling. High blood K^1 and low blood Ca^2 1 can thus cause the
heart to stop in diastole. Conversely, low blood K^1 and high
blood Ca^2 1 can arrest the heart in systole.
The term congestive is often used in describing heart fail-
ure because of the increased venous volume and pressure that
results. Failure of the left ventricle, for example, raises the left
atrial pressure and produces pulmonary congestion and edema.
This causes shortness of breath and fatigue; if severe, pulmo-
nary edema can be fatal. Failure of the right ventricle results in
increased right atrial pressure, which produces congestion and
edema in the systemic circulation.
The compensatory responses that occur during congestive
heart failure are similar to those that occur during hypovolemic
shock. Activation of the sympathoadrenal system stimulates
cardiac rate, contractility of the ventricles, and constriction of
arterioles. As in hypovolemic shock, renin secretion is increased
and urine output is reduced. The increased secretion of renin
and consequent activation of the renin-angiotensinaldosterone
system causes salt and water retention. This occurs despite an
increased secretion of atrial natriuretic peptide (which would
have the compensatory effect of promoting salt and water
excretion).
As a result of these compensations, chronically low cardiac
output is associated with elevated blood volume and dilation and
hypertrophy of the ventricles. These changes can themselves be
dangerous. Elevated blood volume places a work overload on the
heart, and the enlarged ventricles have a higher metabolic require-
ment for oxygen. These problems are often treated with drugs
that increase myocardial contractility (such as digitalis, described
in chapter 13), drugs that are vasodilators (such as nitroglycerin),
drugs that block beta-adrenergic receptors (to reduce the strain
on the heart from excessive sympathoadrenal activation), and
drugs that reduce the effects of excessive activation of the renin-
angiotensin system. The latter includes ACE (angiotensin con-
verting enzyme) inhibitors and ARBs (angiotensin II receptor
blockers). Diuretics—drugs that lower blood volume by increas-
ing urine volume (chapter 17, section 17.6)—are also used to
alleviate congestive heart failure.