All metabolic functions are increased during pregnancy to provide for the demands of fetus, placenta and uterus as well as for the gravida's increased basal metabolic rate and oxygen consumption. Protein metabolism is enhanced to supply substrate for maternal and fetal growth. Fat metabolism increases as evidenced by elevation in all lipid fractions in the blood. Carbohydrate metabolism, however, demonstrates the most dramatic changes. Metabolically speaking, pregnant women live in a state of "accelerated starvation." First, nutritional demands of the growing fetus are met by the intake of glucose and, second, secretion of insulin in response to glucose is augmented. As early as 15 weeks of gestation, maternal blood glucose levels after an overnight fast are considerably lower than in the nongravid state.

Renal plasma flow and glomerular filtration rate begin to increase progressively during the first trimester. At term, both are 50-60% higher than in the non-pregnant state. This parallels the increases in blood volume and cardiac output. The elevations in plasma flow and glomerular filtration result in an elevation in creatinine clearance. Blood urea and serum creatinine are reduced by 40%. The increase in glomerular filtration may overwhelm the ability of the renal tubules to reabsorb leading to glucose and protein losses in the urine. Thus, mild glycosuria (1-10 gm/day) and/or proteinuria (to 300 mg/day) can occur in normal pregnancy. There is also an increase in filtered sodium, but tubular absorption is increased by an increase in aldosterone secretion, via the renin-angiotensin mechanism (see  Physiology of the Kidney). There is also a decrease in plasma osmolality. This is a measure of the osmotic activity of a substance in solution and is defined as the number of osmoles in a kilogram of solvent. In practice it indicates that the plasma concentrations of electrolytes, glucose and urea, fall if more water than sodium, for example, is retained. Over the whole period of gestation there is retention of 7.5L of water and 900 mmol of sodium.

After the 12th week of gestation, progesterone can induce dilation and atony of the renal calyses and ureters. With advancing gestation, the enlarging uterus can compress the ureters as they cross the pelvic brim and cause further dilatation by obstructing flow. These changes may contribute to the frequency of urinary tract infections during pregnancy. The effect of postural compression of the aortic branches perfusing the kidneys has been discussed. 
 
Drug Responses

The response to anaesthetic and adjuvant drugs is modified during pregnancy and the early puerperium. The most pertinent alteration is a reduced drug requirement, manifest in both regional and general anaesthesia.

Regional Anaesthesia. From the late first trimester to the early puerperium, a smaller dose of local anaesthetic is required to obtain the desired level of spinal or extradural blockade. During the last months of gestation, approximately two-thirds of the normal dose is adequate. This altered response, which is due to CSF and hormonal changes and an increase in volume of the epidural veins, subsides progressively in the early postpartum period.

General Anaesthesia. Induction and changes in depth of inhalation anaesthesia occur with greater rapidity in pregnant women than in non-pregnant subjects. Pregnancy enhances anaesthetic uptake in two ways. The increase in resting ventilation delivers more agent into the alveoli per unit time, while the reduction in functional residual capacity favors rapid replacement of lung gas with the inspired agent. In addition, there is a reduction in anaesthetic requirements, with a fall in the minimum alveolar concentrations (MAC) of halogenated vapors. When measured in ewes MAC was 25-40% lower in gravid as compared with nonpregnant animals.

The decreased functional residual capacity has a further effect on the management of general anaesthesia. As referred to earlier, the resultant reduction in oxygen storage capacity, together with the elevated oxygen consumption, leads to an unusually rapid decline in arterial oxygen tension in the apnoeic anaesthetised gravida.

There are also alterations in the response to intravenous agents, in particular prolongation of their elimination half-lives consequent to the greater distribution volume (resulting from the pregnancy-induced increase in plasma volume). Thus, the mean elimination half-life for thiopentone in gravid women is more than doubled in comparison with that in nongravid young patients.

Serum Cholinesterase. Serum cholinesterase levels fall by 24-28% during the first trimester without a marked change for the remainder of gestation. However, even lower levels (about 33% reduction) develop during the first 7 postpartum days. The decreased levels of the enzyme are still sufficient for normal hydrolysis of clinical doses of suxamethonium or chloroprocaine during gestation. Postpartum, however, approximately 10% of women will be at risk of a prolonged reaction to suxamethonium.

Clinical Implication. These altered drug responses must be taken into consideration whenever a patient is pregnant or in the early puerperium. 

This article contained links to the following additional information:

 Issue 9 - Physiology of the kidney

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