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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 2, March/April 2016
AFRICA
91
The increased renal blood flow leads to an increase in renal
size of 1–1.5 cm, reaching the maximal size by mid-pregnancy.
The kidney, pelvis and calyceal systems dilate due to mechanical
compressive forces on the ureters. Progesterone, which reduces
ureteral tone, peristalsis and contraction pressure, mediates these
anatomical changes.
11
The increase in renal size is associated with
an increase in renal vasculature, interstitial volume and urinary
dead space. There is also dilation of the ureters, renal pelvis
and calyces, leading to physiological hydronephrosis in over
80% of women.
12
There is often a right-sided predominance of
hydronephrosis due to the anatomical circumstances of the right
ureter crossing the iliac and ovarian vessels at an angle before
entering the pelvis. Urinary stasis in the dilated collecting system
predisposes pregnant women with asymptomatic bacteriuria to
pyelonephritis.
12
There are also alterations in the tubular handling of wastes
and nutrients. As in the non-pregnant state, glucose is freely
filtered in the glomerulus. During pregnancy, the reabsorption of
glucose in the proximal and collecting tubule is less effective, with
variable excretion. About 90% of pregnant women with normal
blood glucose levels excrete 1–10 g of glucose per day. Due to the
increases in both GFR and glomerular capillary permeability to
albumin, the fractional excretion of protein may increase up to 300
mg/day and protein excretion also increases. In normal pregnancies
the total protein concentration in urine does not increase above
the upper normal limit. Uric acid excretion also increases due to
increased GFR and/or decreased tubular reabsorption.
11
Body water metabolism
Arterial under-filling in pregnancy leads to the stimulation of
arterial baroreceptors, activating the RAA and the sympathetic
nervous systems. This results in a non-osmotic release of AVP
from the hypothalamus. These changes lead to sodium and
water retention in the kidneys and create a hypervolaemic, hypo-
osmolar state characteristic of pregnancy.
6
Extracellular volume
increases by 30–50% and plasma volume by 30–40%. Maternal
blood volume increases by 45% to approximately 1 200 to 1 600
ml above non-pregnant values. By the late third trimester the
plasma volume increases by more than 50–60%, with a lower
increase in red blood cell mass, and therefore plasma osmolality
falls by 10 mosmol/kg. The increase in plasma volume plays
a critical role in maintaining circulating blood volume, blood
pressure and uteroplacental perfusion during pregnancy.
13
Activation of the RAA system leads to increased plasma
levels of aldosterone and subsequent salt and water retention in
the distal tubule and collecting duct. In addition to the increased
renin production by the kidneys, ovaries and uteroplacental
unit produce an inactive precursor protein of renin in early
pregnancy.
14
The placenta also produces oestrogens that
stimulate the synthesis of angiotensinogen by the liver, resulting
in proportionally increased levels of aldosterone compared to
renin. Plasma levels of aldosterone correlate well with those of
oestrogens and rise progressively during pregnancy. The increase
in aldosterone is responsible for the increase in plasma volume
during pregnancy.
13
Progesterone, which is a potent aldosterone
antagonist, allows natriuresis despite the sodium-retaining
properties of aldosterone. The rise in GFR also increases
distal sodium delivery, allowing excretion of excess sodium.
Progesterone has antikaliuretic effects and therefore excretion of
potassium is kept constant throughout pregnancy due to changes
in tubular reabsorption, and total body potassium increases
during pregnancy.
6,15
Hypothalamic AVP release increases early in pregnancy as a
result of increased relaxin levels. AVP mediates an increase in water
reabsorption via aquaporin 2 channels in the collecting duct. The
threshold for hypothalamic secretion of AVP and the threshold
for thirst is reset to a lower plasma osmolality level, creating the
hypo-osmolar state characteristic of pregnancy. These changes are
mediated by human chorionic gonadotropin (hCG) and relaxin.
11,16
In middle and late pregnancy there is a four-fold increase in
vasopressinase, an aminopeptidase produced by the placenta.
These changes enhance the metabolic clearance of vasopressin
and regulate the levels of active AVP. In conditions of increased
placental production of vasopressinase, such as pre-eclampsia or
twin pregnancies, a transient diabetes insipidus may develop.
17
As a consequence of this volume expansion, the secretion of
atrial natriuretic peptides increases by 40% in the third trimester,
and rises further during the first week postpartum. The levels of
natriuretic peptides are higher in pregnant women with chronic
hypertension and pre-eclampsia.
18
Respiratory changes
There is a significant increase in oxygen demand during normal
pregnancy. This is due to a 15% increase in the metabolic rate
and a 20% increased consumption of oxygen. There is a 40–50%
increase in minute ventilation, mostly due to an increase in
tidal volume, rather than in the respiratory rate. This maternal
hyperventilation causes arterial pO
2
to increase and arterial
pCO
2
to fall, with a compensatory fall in serum bicarbonate to
18–22 mmol/l (see Table 1). A mild fully compensated respiratory
alkalosis is therefore normal in pregnancy (arterial pH 7.44).
Diaphragmatic elevation in late pregnancy results in decreased
functional residual capacity but diaphragmatic excursion and
therefore vital capacity remain unaltered. Inspiratory reserve
volume is reduced early in pregnancy, as a result of increased
tidal volume, but increases in the third trimester, as a result of
reduced functional residual capacity (see Fig. 1). Peak expiratory
flow rate (PEFR) and forced expiratory volume in one second
(FEV
1
) are unaffected by pregnancy.
Pregnancy may also be accompanied by a subjective feeling of
breathlessness without hypoxia. This is physiological and is most
common in the third trimester but may start at any time during
gestation. Classically, the breathlessness is present at rest or while
talking and may paradoxically improve during mild activity.
Adaptive changes in the alimentary tract
Nausea and vomiting are very common complaints in pregnancy,
affecting 50–90% of pregnancies.
19
This might be an adaptive
Table 1. Reference ranges for respiratory function in pregnancy
Investigations
Normal values
Pregnant
Non-pregnant
pH
7.40–7.47
7.35–7.45
pCO
2
, mmHg (kPa)
≤ 30 (3.6–4.3)
35–40 (4.7–6.0)
pO
2
, mmHg (kPa)
100–104 (12.6–14.0)
90–100 (10.6–14.0)
Base excess
No change
+2 to –2
Bicarbonate (mmol/l)
18–22
20–28