Pregnancy

Definitions & Key takeaways

Pregnancy, or gestation, is the period during which one or more offspring develop inside a woman. If an ovum is fertilized by a sperm, the fertilized ovum begins to divide and becomes a fetus. The period of development of a fetus is called pregnancy, and in humans, it lasts 40 weeks. During pregnancy, both estrogen and progesterone hormones rise, which causes several changes in nearly every organ system - there's an increase in blood volume, increased urinary output, shallow breathing, mood changes, nausea and changes in taste, darkening of the skin, breast changes, and the loosening of the ligaments. All of which help prepare for the delivery of a healthy baby.

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Pregnancy is an amazing process that affects almost every body system. Throughout the pregnancy, estrogen and progesterone levels steadily rise, and it leads to a number of anatomic and physiologic changes that occur throughout the body.
Everything starts with ovulation, so let’s call that day 0. On that day, in the ovary, an ovarian follicle – which is an egg or oocyte plus its surrounding tissues– matures and ovulation occurs which is when the egg gets ejected while the surrounding structure becomes the corpus luteum and quickly starts making estrogen and progesterone.
Normally, the egg gets fertilized by a sperm within 12-24 hours to form a zygote, so let’s say that fertilization happens a day later on day 1.
Almost right away, cells start to divide over and over, until there’s a ball of cells called the blastocyst on day 4. The blastocyst typically floats around inside the uterus for another day before it finds a specific spot to implant on day 5.
Around this time, the corpus luteum makes a lot more progesterone relative to estrogen, and the low estrogen to progesterone ratio is necessary for implantation.
At this early stage, there are two parts to the blastocyst - an inner set of cells that go on to become the fetus, and an outer set of cells called the trophoblast that burrow into the endometrium on day 6 and eventually develop into the fetal part of the placenta.
That trophoblast cells start to produce a hormone called human chorionic gonadotropin or HCG around day 8, and this is important for two reasons.
One - it’s the hormone that lets the corpus luteum know that there has been a successful implantation into the endometrium, and that it should continue to make estrogen and progesterone.
And it’s the continued presence of estrogen and progesterone that suppresses other ovarian follicles from maturing. Two - HCG is the hormone that most pregnancy tests are able to detect, causing the little sign to form which can happen as early as day 9.
Without HCG levels shooting up on day 8, the corpus luteum would start to shrivel up by day 10, and estrogen and progesterone levels would fall.
This would cause the lining of the endometrium to slough off or fall away from the endometrial wall resulting in a period or menses.
A pregnancy lasts 40 weeks, roughly 9 months, but that is from the last menstrual period, which is usually about 2 weeks before “day 0” of ovulation.
So if you’re counting from “day 0” a pregnancy is only about 38 weeks. The reason for adding in the extra two weeks is that women usually know the date when their last menstrual period began, but have no way of knowing when they ovulated.
So during the first trimester, which is between week 1 through 13, hormones are being generated by the corpus luteum - mainly estrogen and progesterone.
By around week 9, HCG levels peak, and then begin to fall off which is a signal for the corpus luteum to finally start shriveling up.
Luckily, just as the corpus luteum is shriveling up, the placenta takes over, and specialized trophoblast cells called syncytiotrophoblast cells, make progesterone and estriol which is the most abundant type of estrogen.
The placenta also makes a bit of HCG, as well as another hormone called human placental lactogen or hPL which counters the effect of maternal insulin to help ensure that there’s plenty of glucose available in the blood for the fetus.
Many of the changes in pregnancy are directly related to the growth of the uterus. The uterus is normally a pelvic organ, but during pregnancy it grows into the abdomen, rising to the level of the umbilicus by 20 weeks gestation and to the xiphoid process by 36 weeks.
The fundal height - which is the distance from the symphysis pubis to the top of the uterus aka the fundus is a good estimate of gestational age; for example, here at 36 weeks you might expect it to be about 36 cm, but at 20 weeks it’d be closer to 20 cm.
To accommodate the needs of mom, an enlarging uterus, and a growing fetus - as well as having some reserve for the blood loss that happens during delivery, the cardiovascular system has to expand.
Pregnancy is called a high volume state because the circulating blood volume increases by 30-50%, which means that an average woman will go from having 5 liters of blood to about 7.5 liters of blood by the third trimester.
The number of red blood cells increases a bit, but there’s a much larger increase in the plasma volume - the portion of blood that doesn’t have red blood cells.
So the hematocrit, or percentage of blood made of red blood cells, actually goes down. This is called “physiological anemia of pregnancy”.
To push this extra blood around, the heart rate goes up by about 20 beats per minute, so this increases the cardiac output.
In response to the increased workload there is a mild hypertrophy of the heart, which does go away after pregnancy. The high volume state also explains why there’s sometimes a third heart sound or physiologic S3, as well as a split S1 which is where the mitral valve closes slightly faster than the tricuspid valve.
Finally, the blood pressure actually falls a tiny bit, even though more blood’s getting pushed through them, since progesterone causes them to dilate.
Finally, as the uterus enlarges, it pushes up on the diaphragm, nudging the heart slightly upward and shifting the heart’s point of maximum intensity - the spot where it taps against the chest wall - a little bit to the left.
The uterus also presses against the pelvic veins, causing blood to back up, leading to varicose veins as well as swelling in the lower legs and ankles.
When lying down, the uterus presses on the inferior vena cava reducing blood flow back to the right atrium and causing hypotension.
A side-lying position or placing a pillow under the hip can help avoid that. The increased cardiac output also means that there more fluid going through the kidneys, increasing the glomerular filtration rate and urinary output.
Combining that increased urine output with direct pressure on the bladder from the enlarging uterus, explains why pregnant women have urinary frequency.
It turns out that the kidneys compensate for the extra workload by increasing in size causing the calyces and renal pelvis to dilate - resulting in physiologic hydronephrosis, and increasing size of the ureters, causing physiologic hydroureter.
In addition, progesterone causes hypomotility of the ureters. The increased capacity to store urine and the hypomotility in the ureters results in urinary stasis in the kidneys and increases the risk of an upper urinary tract infection.
The lungs get affected as well. The uterus pushes upwards on the diaphragm, making it harder for pregnant women to breathe comfortably.
There’s some compensation because progesterone relaxes ligaments in the thorax, increasing the transverse diameter of the rib cage - like a bucket handle that swings out, and the anteroposterior diameter of the rib cage - like a handle that pulls up.
These changes increase the tidal volume - the amount of air inhaled or exhaled per breath - and minute volume - the amount of air inhaled or exhaled per minute.
This decreases carbon dioxide levels in the blood causing a mild respiratory alkalosis. It turns out that this mild alkalosis actually enhances gas exchange across the placenta, making it easier for the growing fetus to get oxygen.
Finally, in the upper respiratory tract, estrogen causes increased vascularization and capillary engorgement, which can lead to nasal stuffiness, sinus congestion, and nosebleeds.
In addition, progesterone and relaxin, another hormone produced by the placenta, both loosen ligaments around the sacroiliac joints and symphysis pubis in preparation for fetal passage through the birth canal.
This results in a waddling gait sometimes seen during pregnancy, and these two can also cause pain in other joints, like those of the ribs and, or coccygeal or tail bone, all from shifting ligaments.
In the gastrointestinal tract, hormonal changes cause smooth muscle relaxation and decreased peristalsis, which sometimes leads to constipation and bloating - stool softeners might help with this.
It also causes relaxation of the lower esophageal sphincter, which can lead to gastric reflux and heartburn - which can be managed with proton pump inhibitors, like omeprazole .
Many pregnant women also experience “morning sickness” which is nausea that typically happens early on in the pregnancy, but can actually happen any time of day and sometimes persists throughout the pregnancy.
Pyridoxine, or vitamin B6, can help with the nausea - if not effective, a combination of doxylamine succinate and pyridoxine might do the trick.
Tastes can change too - some women start disliking certain foods while craving other ones. A classic example is called pica, where there’s a craving for non-food items like ice, dirt, or starch; the exact cause of this is unclear.
High levels of estrogen and progesterone hormones can also affect mood, and the effect can range from mild irritability to severe anxiety and depression, all of which can be very unexpected and disconcerting.
Many women also describe a mental fogginess or decreased ability to concentrate, which may be related to hormonal changes or general fatigue and sleep deprivation.
During the pregnancy, estrogen and progesterone also promote breast development and the milk-producing machinery that will go to work after the baby is delivered.
Increased blood flow to the breasts and building of breast tissue may cause symptoms like tingling, fullness, and tenderness.
Estrogen also stimulates the anterior pituitary to produce prolactin, a hormone responsible for milk production and letdown, though the high levels of progesterone present during pregnancy inhibit prolactin’s milk letdown effect until the baby is born and estrogen and progesterone levels fall.
That anterior pituitary gland also releases more melanocyte stimulating hormone, which causes darkening of the areolae, or the skin around the nipples.
The increased melanocyte activity also darkens the normally unseen stripe of fibrous tissue running down the chest and abdomen from the xiphoid process to the symphysis pubis called the linea alba or white line, transforming it into a darkened line called the linea nigra.
Other glands that are affected by pregnancy include the thyroid gland which churns out more thyroid hormone to increase the cellular basal metabolic rate in order to meet the demands of the pregnancy.
Finally, estrogen also promotes blood clotting by increasing plasma fibrinogen and the activity of coagulation factors, as well as enhancing platelet aggregation - all of which normally promote coagulation.
At the same time, estrogen decreases the activity of antithrombin III, which normally inhibits coagulation. Therefore, pregnancy is a hypercoagulable state - and it makes sense for it to be this way, so there will be as little bleeding after delivery as possible.
However, this also means pregnant females have a greater risk of developing a venous thromboembolism, meaning a blood clot blocking off a vein - especially in the lower legs, where there’s already venous stasis.
Normally, women gain 25 to 35 pounds throughout the pregnancy, and that extra weight is mostly due to the increased blood volume, followed by the fetus itself, fat stores, the uterus, and finally the placenta.
The extra weight and the forward shift in the center of gravity, can cause a lordosis and lower back pain. Women can also get diastasis recti, which is where the uterus puts direct pressure on rectus abdominus muscles making them separate.
In general, this pain can make it tough to get a good night’s rest. As a quick recap, during pregnancy, both estrogen and progesterone rise, which causes a number of changes in nearly every organ system - there’s an increase in blood volume, increased urinary output, shallow breathing, mood changes, nausea and changes in taste, darkening of the skin, breast changes, and the loosening of the ligaments.
All of which help prepare for the delivery of a healthy baby.