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SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
VOLUME 16 NUMBER 1 • JULY 2019
5
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 lifethreatening 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 associatedwith 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
The development of symptoms, an uncontrollable spike in
blood pressure or the evolution of defined organ dysfunction
signal the onset of life-threatening disease, requiring that the focus
of treatment shift from the neonatal outcome to protecting the
interests of the mother. Delivery at this point is inevitable and the