Physiological Changes in Pregnancy

Introductory Comments
This lecture/presentation is a “work in progress”
Not possible to cover “all” the changes that occur during pregnancy!
We will highlight some of the important changes that occur, affecting some of the major organ systems
Key concept: one needs to know “normal” to be able to diagnose and manage the common problems in pregnancy!
This may be of personal importance some day!

Physiological Adaptations to Pregnancy
Numerous normal changes in response to pregnancy
It is important to have an awareness of what is considered “normal” in pregnancy
Such awareness allows an obstetrician to diagnose and manage common medical problems such as
Hypertension
Hyperthyroidism
Anemia
Acute appendicitis or acute cholecystitis
Peripartum cardiomyopathy
Mitral stenosis
Asthma
Gestational diabetes or Insulin dependent diabetes

Weight Gain in Pregnancy
Normal weight gain can be 30-35 lbs in average patient and 50-70 lbs. in twin pregnancy
Daily requirements of 2000-2500 calories
Associated with good outcome, ie delivery of normal sized baby
Excess weight gain associated with variety of complications:
GDM, pre-eclampsia, macrosomia
Total pregnancy expenditure is 75,000kcalories
Recommendations for appropriate weight gain in pregnancy based on initial weight, BMI

Weight Gain in Pregnancy

Weight Gain in Pregnancy

Breast Changes
Increased blood flow to breasts
Increased size
Increased ductal growth, alveolar enlargement
Colustrum production
Lactation dependent on
Estrogen
Progesterone
Prolactin
Cortisol
Insulin

Musculoskeletal Changes in Pregnancy
Ligament laxity throughout
Progressively more bothersome backpain not uncommon
“Pride of pregnancy”
Total calcium levels decreased but ionized calcium levels normal
Increased PTH
Increased relaxin
No loss of bone density during pregnancy

Skin Changes
Vascular spiders
Palmar erythema
Striae gravidarum
Hyperpigmentation effects
Linea nigra
Mask of pregnancy
Increased fine hair growth while pregnant
Pruritus at end of pregnancy with cholestasis

Gastrointestinal Changes
Key Changes
Appetite Usually increased, with cravings
Gastric Reflux Sphincter relaxation
GI Motility Decreased
GI Transit Time Slower
Liver Functionally unchanged
Gallbladder Dilated

Common GI Changes in Pregnancy
Nausea and vomiting of pregnancy or “morning sickness”
Exact etiology is unknown
Supportive therapy usually helpful
On rare occasion, TPN and hyperalimentation necessary
Dietary cravings commonplace
Pica
Ptyalism
Increased tendency for gallbladder dysfunction with possible need for surgery, or laporoscopic cholecystectomy

Physiological GI Changes.
The hormonal effects on the gastrointestinal tract are an issue of debate among anaesthetists. Relaxation of the lower oesophageal sphincter has been described, but there have been differing views about the effect on motility of the gastrointestinal tract and the times at which it is most prominent. Many believe that there is also retardation of gastrointestinal motility and gastric emptying, producing increased gastric volume with decreased pH, beginning as early as 8-10 weeks of gestation.

Physiological GI Changes
Recent studies, however, have shed a different light on the subject. Measuring peak plasma concentrations of drugs absorbed exclusively in the duodenum in both non-pregnant and pregnant volunteers, at different times of gestation, it was shown that peak absorption occurred at the same interval in all women with the exception those in labour. This suggests that gastric emptying is delayed only at the time of delivery.

Hepatic Function Laboratory Studies

Hematological Changes in Pregnancy
Plasma volume increases early in pregnancy with a 50% increase (and higher in higher order multiple pregnancies) and a delayed increase in RBC mass and volume but less than the plasma volume
Normal pregnancy associated with a “demand” of 1000 milligrams of additional iron
500 mg. to increase maternal RBC volume
300 mg. tranpsorted to fetus
200 mg. for normal iron loss
60 mg. of elemental iron required daily, provided in 300 mg. of ferrous sulfate
Serum iron decreased
Transferrin and TIBC are increased

More Hematological Changes Occurring During Pregnancy
Pregnancy considered a “hypercoagulable state”
Fibrinogen increases to 450-600 mg/dl
Factors VII, VIII, IX and X increase
Prothrombin, Factor V, and XII are unchanged
Bleeding time does not change
Platelet count may increase to 450,000 to 600,000
WBC count may increase to as high as 20,000 due to an increase in granulocytes

Pulmonary Adaptations
Anatomical
Increased chest diameter, subcostal angle changes, increased diaphragmatic excursion with diaphragm elevated as well
Physiological
Hyperventilation, Increased IC,VC and Minute Volume, Residual volume decreased, Expiratory Reserve Volume decreased Tidal volume increased by 40%, pO2 increased, pCO2 decreased, arterial pH unchanged, and serum bicarbonate reduced

Ventilation and Respiratory Gases.
A progressive increase in minute ventilation starts soon after conception and peaks at 50% above normal levels around the second trimester. This increase is effected by a 40% rise in tidal volume and a 15% rise in respiratory rate (2-3 breaths/minute). Since dead space remains unchanged, alveolar ventilation is about 70% higher at the end of gestation.

Ventilation and Respiratory Gases.
Arterial and alveolar carbon dioxide tensions are decreased by the increased ventilation. An average PaCO2 of 32 mmHg (4.3 kPa) and arterial oxygen tension of 105 mmHg (13.7 kPa) persist during most of gestation. The development of alkalosis is forestalled by compensatory decreases in serum bicarbonate. Only carbon dioxide tensions below 28 mmHg (3.73 kPa) will lead to a respiratory alkalosis.

Ventilation and Respiratory Gases
Oxygen consumption increases gradually in response to the needs of the growing fetus, culminating in a rise of at least 20% at term. During labour, oxygen consumption is further increased (up to and over 60%) as a result of the exaggerated cardiac and respiratory work load.

Cardiac Changes in Pregnancy
Cardiac output increases around 50% from an increase in HR and SV (3L/min to 6.2L/min)
There is an additional 40% increase above that level during active labor
Immediately following delivery, cardiac output may be increased by an additional 10-20%
Cardiac exam is different during pregnancy
Many patients will have an S3 after midpregnancy
Diastolic murmurs are usually considered serious
Systolic murmurs (“flow murmurs”) common
Displacment of heart is to right and upwards
EKG shows left axis deviation and low voltage QRS complexes

Key Cardiovascular Changes During Pregnancy

Blood Volume
Blood Volume increases progressively from 6-8 weeks gestation (pregnancy) and reaches a maximum at approximately 32-34 weeks with little change thereafter. Most of the added volume of blood is accounted for by an increased capacity of the uterine, breast, renal, striated muscle and cutaneous vascular systems, with no evidence of circulatory overload in the healthy pregnant woman. The increase in plasma volume (40-50%) is relatively greater than that of red cell mass (20-30%) resulting in hemodilution and a decrease in haemoglobin concentration. Intake of supplemental iron and folic acid is necessary to restore hemoglobin levels to normal (12 g/dl).

Blood Volume
The increased blood volume serves two purposes. First, it facilitates maternal and fetal exchanges of respiratory gases, nutrients and metabolites. Second, it reduces the impact of maternal blood loss at delivery. Typical losses of 300-500 ml for vaginal births and 750-1000 ml for Caesarean sections are thus compensated with the so-called "autotransfusion" of blood from the contracting uterus

Blood Constituents.
As mentioned above, red cell mass is increased 20-30%. Leukocyte counts are variable during gestation, but usually remain within the upper limits of normal. Marked elevations, however, develop during and after parturition (delivery). Fibrinogen, as well as total body and plasma levels of factors VII, X and XII increase markedly. The number of platelets also rises, yet not above the upper limits of normal. Combined with a decrease in fibrinolytic activity, these changes tend to prevent excessive bleeding at delivery. Thus, pregnancy is a relatively hypercoagulable state, but during pregnancy neither clotting or bleeding times are abnormal

Cardiac Output
Cardiac Output increases to a similar degree as the blood volume. During the first trimester cardiac output is 30-40% higher than in the non-pregnant state. Steady rises are shown on Doppler echocardiography, from an average of 6.7 litres/minute at 8-11 weeks to about 8.7 litres/minute flow at 36-39 weeks; they are due, primarily, to an increase in stroke volume (35%) and, to a lesser extent, to a more rapid heart rate (15%). There is a steady reduction in systemic vascular resistance (SVR) which contributes towards the hyperdynamic circulation observed in pregnancy.
During labor, further increases are seen with pain in response to increased catecholamine secretion; this increase can be blunted with the institution of labour analgesia. Also during labour, there is an increase in intravascular volume by 300-500 ml of blood from the contracting uterus to the venous system. Following delivery this autotransfusion compensates for the blood losses and tends to further increase cardiac output by 50% of pre-delivery values. At this point, stroke volume is increased while heart rate is slowed.

Cardiac Output
During labor, further increases are seen with pain in response to increased catecholamine secretion; this increase can be blunted with the institution of labour analgesia. Also during labour, there is an increase in intravascular volume by 300-500 ml of blood from the contracting uterus to the venous system. Following delivery this autotransfusion compensates for the blood losses and tends to further increase cardiac output by 50% of pre-delivery values. At this point, stroke volume is increased while heart rate is slowed.

Cardiac Size/Position/ECG.
There are both size and position changes which can lead to changes in ECG appearance. The heart is enlarged by both chamber dilation and hypertrophy. Dilation across the tricuspid valve can initiate mild regurgitant flow causing a normal grade I or II systolic murmur. Upward displacement of the diaphragm by the enlarging uterus causes the heart to shift to the left and anteriorly, so that the apex beat is moved outward and upward. These changes lead to common ECG findings of left axis deviation, sagging ST segments and frequently inversion or flattening of the T-wave in lead III.

Blood Pressure
. Systemic arterial pressure is never increased during normal gestation. In fact, by midpregnancy, a slight decrease in diastolic pressure can be recognized. Pulmonary arterial pressure also maintains a constant level. However, vascular tone is more dependent upon sympathetic control than in the nonpregnant state, so that hypotension develops more readily and more markedly consequent to sympathetic blockade following spinal or extradural anaesthesia. Central venous and brachial venous pressures remain unchanged during pregnancy, but femoral venous pressure is progressively increased due to mechanical factors.

Renal Changes in Pregnancy
Minimal renal enlargement, bilaterally
Both renal pelvises and ureters are dilated (“hydronephrosis of pregnancy”)
Greater urinary stasis, ureteral compression, leading to urinary stasis and possilbe urinary tract infections, pyelonephritis
Loss of urinary control
Bladder capacity diminished
RPF increases to 75% of non-pregnant value

More Renal Changes in Pregnancy
GFR increases 50% over on-pregnant state
Creatinine clearance increases to 150-200 ml/min
Plasma osmolality decreases
Urine output is unchanged
There is an increased sensitivity to renin and angiotensin
Renal glycosuria common
Proteinuria up to 300 mg/24 hours normal

Endocrine Changes with Pregnancy
Carbohydrate Metabolism
Overall effect is that pregnancy is diabetogenic
First half: tendency to hypoglycemia
Second half: tendency to hyperglycemia
Progressive insulin resistance as pregnancy progresses
Progesterone
Estrogen
HPL
“Typical” FBS less than in non-pregnant state
Blunting response to meals, eating as pregnancy progresses
Hypertrophy of beta cells as well

Metabolism
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.

Metabolism
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.

Hypoglycaemia.
Optimal blood glucose levels in pregnant women range between 4.4 to 5.5 mmol/1. In healthy non-pregnant individuals, signs of hypoglycaemia usually begin when the blood glucose level declines to approximately 2.2 mmol/1 (40mg/dl); in pregnant women, however, hypoglycaemia is defined as a concentration below 3.3 mmol/1 (60mg/dl).

Hypoglycaemia.
Hypoglycaemia initiates the release of glucagon, cortisol and, importantly, catecholamines. In the anaesthetised state, however, these compensatory mechanisms, particularly the release of epinephrine (adrenaline), are blocked. Autonomic derangements in the form of hypotension and tachycardia tend to ensue during high regional blockade or deep general anaesthesia, which may mask the symptoms and signs of hypoglycaemia

Endocrine Changes in Pregnancy
Thyroid Function in Pregnancy
The normal pregnant woman remains euthyroid while pregnant despite/ with hormonal changes which occur
Estrogen production increases
Increased TBG
Increased total thyroxine, and T3
Free T4 and T3 remain unchanged
BMR increases 15-20% above normal
There is lowered T3 uptake during pregnancy
TSH does not cross the placenta

Endocrine Changes in Pregnancy
GnRH concentration increases during pregnancy, but the physiological significance of this change has not been determined
corticotropin-releasing hormone (CRH) is expressed by placental and chorionic trophoblasts, amnion, and decidual cells . Its concentration in maternal circulation is high and rises exponentially throughout pregnancy
Endocrine Changes in Pregnancy

Endocrinology Changes in Pregnancy

Endocrine Changes in Pregnancy
The placenta produces a hormone (similar to thyroid-stimulating hormone) that stimulates the thyroid, causing hyperplasia, increased vascularity, and moderate enlargement. Estrogen stimulates hepatocytes, causing increased thyroid-binding globulin levels; thus, although total thyroxine levels may increase, levels of free thyroid hormones remain normal.

Endocrine Changes in Pregnancy
The placenta produces corticotropin-releasing hormone (CRH), which stimulates maternal ACTH production. Increased ACTH levels increase levels of adrenal hormones, especially aldosterone and cortisol, and thus contribute to edema. Increased production of corticosteroids and increased placental production of progesterone lead to insulin resistance and an increased need for insulin, as does the stress of pregnancy and possibly the increased level of human placental lactogen

Endocrine Changes in Pregnancy
The placenta produces melanocyte-stimulating hormone (MSH), which increases skin pigmentation late in pregnancy. The placenta also produces the β subunit of human chorionic gonadotropin (β-hCG), a trophic hormone that, like follicle-stimulating and luteinizing hormones, maintains the corpus luteum and thereby prevents ovulation.

Endocrine Changes in Pregnancy
Effects of thyroid hormone tend to increase and may resemble hyperthyroidism, with tachycardia, palpitations, excessive perspiration, and emotional instability. However, true hyperthyroidism occurs in only 0.08% of pregnancies