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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 2, March/April 2016
AFRICA
105
Hypertension is defined in different ways but the most widely
accepted definition is the sustained elevation of diastolic blood
pressure above 90 mmHg over a period of four hours. Proteinuria
is similarly defined in different ways but dipstick proteinuria of 1+
or more merits further investigation. The 24-hour urinary excretion
of protein greater than 300 mg is regarded as being pathological.
Pre-eclampsia may present in an asymptomatic form. It
may also develop acutely or progress to a phase of illness in
which multi-organ disease becomes evident.
13
This may include
the development of eclampsia, cerebrovascular haemorrhage
leading to stroke, renal failure either in consequence of acute
kidney injury or associated with a progressive decline in renal
function, pulmonary oedema for a variety of reasons, liver injury
in the form of the HELLP syndrome (haemolysis, elevated liver
enzymes and low platelets) or obstetric haemorrhage caused by
abruptio placentae (commonly associated with pre-eclampsia).
Many of these complications of pre-eclampsia may be life-
threatening to the foetus and the pregnant woman.
14-16
Characteristically, the delivery of the baby signals the onset
of disease resolution, although the mother may continue to
exhibit worsening disease for up to 24 hours after delivery. The
hypertension associated with pre-eclampsia may take up to six
weeks to resolve completely, even if the risk of fulminant disease
abates within 24 hours of parturition.
Pathology and pathophysiology
Pre-eclampsia is a disease of defective placentation.
6
The vascular
adaptation in the vessels supplying blood to the placenta show
signs of inadequate dilatation as well as evidence of lumina
pathology, similar to atherosclerosis. The placenta itself is
usually small and infarcted to a greater extent than is usually
seen in normal pregnancy.
The evolution of the clinical phenotype follows these
pathophysiological events in the placental bed. The precise
mechanisms are not fully elucidated but some combination
of systemic immune activation in response to an increasing
maternal circulatory burden of trophoblastic tissue released from
the ischaemic placenta combines with components of oxidative
stress and an imbalance in the production of angiogenic and
anti-angiogenic factors to give rise to changes in systemic
vascular endothelial function.
17,18
The volume-overloaded circulation of normal pregnancy
is offset by endothelial-dependent vasodilatation to such an
extent that normal pregnancy is characterised by falling blood
pressure, despite the volume overload.
19
In pre-eclampsia, the
endothelial mechanism is disrupted and hypertension based
upon vasoconstriction ensues. The pattern of hypertension may
evolve through stages where the increased systemic pressure may
be partly based upon increased cardiac output, compensatory for
the diminished perfusion of the placenta through narrow vessels
in the placental bed.
20
The later evolution of the disease is due
to defective vasoregulation and vasoconstriction associated with
loss of intravascular volume through leaky capillaries and the
onset of multi-organ ischaemia.
21-25
Specific organs show patterns of ischaemic change, and
haemorrhage with or without oedema. These include the brain,
kidneys, placenta and liver.
26-28
In the brain, the oedema is seen
in the watershed areas of perfusion of the occipital lobe and
has been designated as ‘posterior reversible encephalopathy
syndrome’.
29
Large haemorrhages can arise from ruptured vessels,
with consequent mass effects, including tonsillar herniation,
leading to death. The liver shows periportal ischaemia and
haemorrhage in women with the HELLP syndrome, whereas the
kidneys show evidence of endotheliosis, associated in some cases
with acute tubular and cortical ischaemic damage.
21,28
The cardiovascular and pulmonary changes seen are those of
pulmonary oedema in severe cases, usually without other overt
signs of heart failure.
13,30
Risk of morbidity and mortality
There are two major causes of death among women with
pre-eclampsia, cerebrovascular haemorrhage and pulmonary
oedema, and each account for roughly half the number of
deaths.
16
Other rarer causes include the rupture of a subcapsular
haematoma, which may complicate the HELLP syndrome.
Cerebrovascular haemorrhage is related to severe
hypertension.
31
The threshold above which this risk escalates is the
mean arterial pressure above which the cerebral autoregulatory
function fails. This is commonly considered to be 140 mmHg. It is
unusual for women to develop such severe hypertension without
associated seizure activity. The development of eclampsia leads
to severe hypertension during seizure activity and it is the reason
why the case fatality rate for eclampsia is cited as one in 50,
whereas the overall case fatality rate of pre-eclampsia is set at
one in 1 500.
14,32
The prevention of eclampsia is as important as
the treatment of severe hypertension.
Pulmonary oedema may develop for different reasons. The
iatrogenic administration of excessive amounts of intravenous
fluids may lead to an absolute increase in preload, resulting
directly in interstitial pulmonary oedema.
13,22
A very high systemic
vascular resistance can also elevate the pulmonary capillary
wedge pressure, leading to an increased risk of pulmonary
oedema.
33
The left ventricular function may also be abnormal and
commonly demonstrates some degree of diastolic dysfunction,
although left ventricular systolic dysfunction is unusual.
22,23
The loss of protein in the urine may lower the colloid osmotic
pressure and contribute to development of the generalised oedema
so characteristic of pre-eclampsia, with similar effects on the lungs.
Changes in capillary permeability and the lymphatic drainage of the
lungs all modulate the risk of pulmonary oedema in women with
variable changes in vascular resistance and ventricular function.
Consequently, the precise mechanism of pulmonary oedema cannot
be simply attributed to heart failure in this condition.
Management principles
Pre-eclampsia is not a condition that can be managed adequately
outside a hospital environment.
4
The definitive management of
pre-eclampsia is delivery.
4
Once manifest, the condition tends to
worsen and it is unusual for delivery to be delayed by more than
10 to 14 days once the patient develops symptoms or signs of
the condition. Because the foetus is at risk of impaired growth
and likely to deliver prematurely, management needs to take
place in an obstetric unit with access to the best available level
of paediatric care. Any improvement in neonatal outcome can
only be secured by minimising the risks of prematurity. This is
accomplished by delaying delivery for as long as the mother’s
condition can be considered to be satisfactory.
34,35