Medical Physiology: Integration Using Clinical Cases
693
such as elevated body temperature, pulse rate, respiratory rate,
and white blood cell count), the condition is referred to as
sepsis
.
The most common sites of bacterial infections leading
to sepsis are the lungs, abdomen (as in our patient), urinary
tract, and sites where catheters penetrate the skin or blood ves-
sels. If sepsis progresses to septic shock, patients also develop
a signifi
cant decrease in blood pressure (a decrease in systolic
pressure of greater than 40 mmHg or a mean arterial pres-
sure less than 65 mmHg) that is not reversible by intravenous
infusion of large volumes of isotonic saline solution. This type
of circulatory failure is an example of
low-resistance shock
,
as
described in Chapter 12.
Physiological Integration
Bacterial infections stimulate the body to mount a rapid and
widespread defense reaction (see Figure 18–20). Monocytes
and macrophages (two types of white blood cells) secrete a va-
riety of signaling molecules known generally as cytokines (see
Table 18–2), which include substances such as interleukins and
tumor necrosis factor. Target tissues for cytokines include
(1) the brain, where they mediate the onset of fever, a decrease
in appetite, fatigue, and an increase in ACTH secretion; (2) the
bone marrow, where they stimulate an increase in the rate of
white blood cell production; and (3) endothelial cells through-
out the vasculature, where they stimulate processes leading to
infl ammation and increased capillary leakiness. Many species of
bacteria release toxins, which greatly accelerate and exaggerate
cytokine release and effects, often resulting in a maladaptive
or life-threatening over-reaction. The systemic infl ammatory
response has far-reaching effects on all body systems.
Such was the case of our patient by the time he fi nally
reached the hospital. The set point for his body temperature
was reset upward by circulating cytokines, resulting in
fever
,
and he shivered and felt chilled as his body attempted to warm
itself toward the new, higher set point. The onslaught of cyto-
kines and other infl ammatory mediators (see Table 18–4) ac-
celerated as his white blood cell count increased and bacterial
toxins were released into his circulation. Excessive amounts of
those chemicals caused widespread injury to the microvascular
endothelium and led to leakage of fl uid out of capillaries.
When capillaries become excessively leaky, bulk fl ow fa-
vors the exit of fl uid from the circulation (see Figure 12–41).
Plasma proteins escape into the interstitial fl
uid, creating a sig-
nifi cant osmotic force that draws fl uid out through capillary
pores. This is due to Starling forces, which are described in
Chapter 12 (see Figure 12–42). This loss of fl uid causes a dras-
tic reduction in circulating blood volume, to the point where
even baroreceptor refl exes (see Chapter 12, Section D) are un-
able to maintain arterial blood pressure. Dramatic elevation of
heart rate is evidence of activation of the baroreceptor refl exes
via the cardiovascular control centers in the brain to raise blood
pressure toward normal. Even relatively large intravenous fl
uid
infusions fail to reverse this hypotension because much of the
infused fl uid simply escapes into the interstitial space. Accumu-
lation of fl uid in the interstitial space leads to the tissue edema
observed in our patient, and leakiness of pulmonary capillaries
eventually led to fl uid in his lungs (
pulmonary edema
).
Lowered systemic arterial blood pressure makes it dif-
fi cult to produce adequate blood fl ow through the tissues.
When blood fl ow is inadequate to meet demands for oxygen
and nutrients (
ischemia
), tissues, organs and organ systems
malfunction. For example, our patient’s inability to form urine
resulted from low blood fl ow through his kidneys (see Figure
14–20). The increase in serum creatinine was evidence that
glomerular fi ltration rate was decreased (see Figure 14–12).
A more general consequence of reduced oxygen availabil-
ity is that cells must resort to anaerobic pathways to manufac-
ture ATP, and lactic acid (lactate) is produced as a by-product
(see Figure 3–41 and Figure 9–22). This led to the marked
metabolic acidosis seen in our patient. His hyperventilation
was driven by the peripheral and central chemoreceptors, in
an attempt to compensate by removing CO
2
-derived acid from
the plasma (see Figure 13–37). Another mechanism designed
to combat acidosis is the addition of new bicarbonate to the
plasma and the excretion of H
+
via the kidney (Chapter 14,
Section C), but the decrease in renal blood fl ow and glomer-
ular fi
ltration rate rendered this mechanism ineffective. His
oxygen delivery to tissues was further compromised by the
fl uid buildup in his lungs. The added barrier to oxygen diffu-
sion from lung alveoli into pulmonary capillaries (see Figure
13–28) reduced the oxygen partial pressure of his systemic
arterial blood.
Therapy
Septic shock is an extremely challenging condition to treat,
with mortality rates of 40–60 percent. One of the most im-
portant factors in determining patient survival is early recog-
nition of the condition and onset of treatment. As soon as it
has been determined that a patient is septic and is progressing
toward septic shock, survival depends on rapid and continuous
assessment of his or her physiological condition and timely
therapeutic responses to changing conditions. Among the
variables monitored, in addition to those listed in Table 19–3,
are body temperature, heart rate, blood pressure, arterial and
venous oxygen saturation, mean arterial and central venous
blood pressures, urine output, and specifi c biochemical plasma
indicators of the function of other organs, such as the liver.
Using this information, physicians can take steps to improve
cardiovascular and respiratory function while battling the in-
fection that is the root cause of the condition.
Immediate interventions in the treatment of septic shock
are aimed at restoring systemic oxygen delivery and thus re-
lieving the widespread tissue hypoxia that is a hallmark of the
condition. Mean arterial blood pressure is increased by infu-
sions of isotonic saline and by treatment with vasoconstrictors
such as norepinephrine and vasopressin (see Figure 12–51).
The extra circulating fl uid volume increases cardiac output
by increasing venous pressure and cardiac fi lling (see Figure
12–46), whereas norepinephrine (the neurotransmitter nor-
mally released from postsynaptic sympathetic nerve endings)
increases cardiac contractility and arteriolar vasoconstric-
tion (see Figure 12–51). Maintaining mean arterial pressure
between 65 and 90 mmHg is necessary to ensure adequate
fl ow of blood through the tissues. Central venous pressure is
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