GI in Pregnancy: GI in Pregnancy: Hyperemesis and Normal Labs

0:00Welcome to Board Pearls. This is episode one of six of the GI in Pregnancy chapter, in the Special Populations and Acute or Supportive Care module. This episode is normal pregnancy and the first problem many pregnancies bring, nausea and vomiting, followed in one woman pregnant with twins. Her case shows how hyperemesis gravidarum is defined, how her labs are read against the normal changes of pregnancy, why a creatinine of one point zero is a warning, why a raised ALT always needs a cause and what usually causes it, which imaging is safe if it's needed, and how treatment steps up from a vitamin to steroids, with thiamine before any glucose.

0:35Here's the patient. A twenty-nine-year-old woman is nine weeks pregnant with twins, her first pregnancy. For two weeks she's vomited many times a day and can barely keep down water. She's lost four and a half kilograms from a pre-pregnancy weight of sixty-two, and her urine shows ketones. Her potassium is low, her alanine aminotransferase, ALT, is two hundred forty, her aspartate aminotransferase, AST, one hundred eighty, her bilirubin one point six, and her creatinine one point zero.

1:06She has hyperemesis gravidarum, the severe end of nausea and vomiting of pregnancy. Nausea and vomiting affect seventy to eighty percent of pregnancies and usually resolve by week twenty. Hyperemesis gravidarum is defined by persistent vomiting for more than a week, weight loss of more than five percent of pre-pregnancy weight, dehydration with ketonuria, and electrolyte abnormalities, and it affects about zero point three to two percent of pregnancies. Its risk factors are a higher pre-pregnancy weight, a twin pregnancy, and a first pregnancy, and it recurs in about sixty-four percent of later pregnancies. She has two weeks of vomiting, about seven percent weight loss, ketonuria, and a low potassium, with two of the risk factors, twins and a first pregnancy.

1:52Her labs are read against the normal changes of pregnancy, because any change that pregnancy itself doesn't cause is pathologic. Plasma and blood volume rise by about fifty percent, so hemoglobin falls by dilution, and the anemia of pregnancy is largely dilutional. The white count normally rises to twelve to fifteen thousand, and up to twenty-five thousand around delivery. Glomerular filtration rises, so creatinine falls, usually below zero point eight. Her creatinine of one point zero, normal outside pregnancy, is high for her, and with her vomiting it points to dehydration.

2:27Her liver tests follow the same rule. Alkaline phosphatase rises from placental production in the second and third trimesters, often to twice baseline by term, while gamma-glutamyl transferase, GGT, stays low or normal, because estrogen impairs its release from the liver. So an isolated rise in alkaline phosphatase without GGT is expected and comes from the placenta. AST and ALT, by contrast, don't rise in normal pregnancy, because nothing in normal pregnancy raises them, so any elevation is pathologic and needs a cause. Her ALT of two hundred forty is never written off as the pregnancy.

3:07The other liver numbers change in predictable ways. Bilirubin is normal or only slightly raised. Albumin falls by dilution, so a value below three doesn't carry the weight it would in cirrhosis. Cholesterol and triglycerides rise, total bile acids rise mildly, coagulation factors rise in a prothrombotic state, and alpha-fetoprotein rises from the fetus. Estrogen and progesterone also alter hepatic cytochrome P450, so levels of drugs like tacrolimus, cyclosporine, and antiepileptics need monitoring during pregnancy.

3:41Her examination is read against pregnancy norms too. Total liver blood flow is unchanged, though the liver's share of a larger cardiac output falls as flow shifts to the placenta and uterus, and peripheral resistance drops. Telangiectasias and palmar erythema appear in about sixty percent of normal pregnancies from estrogen-driven vasodilation, so they aren't evidence of liver disease. Late in pregnancy, the enlarging uterus can compress the inferior vena cava and cause transient esophageal varices without any liver disease.

4:13Her raised ALT is then weighed against the usual causes of abnormal liver tests in pregnancy. They occur in three to five percent of pregnancies, and the three dominant causes now are gallstone disease, about a quarter; preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets, HELLP, about another quarter; and intrahepatic cholestasis of pregnancy, about one in eight. Viral hepatitis now falls below these because of universal hepatitis B vaccination and hepatitis C screening. At nine weeks, she's too early for preeclampsia or cholestasis of pregnancy, which arise later, and her vomiting is the obvious explanation.

4:52Gallstones top that list because pregnancy makes bile lithogenic. Estrogen raises cholesterol secretion into bile, bile salt secretion falls, and progesterone slows gallbladder contraction and enlarges it, so bile stagnates. About one in ten pregnant women develops stones or sludge, and the change reverses one to two months after delivery.

5:13Her pattern fits hyperemesis. Liver tests are abnormal in up to half of women with hyperemesis gravidarum and in two-thirds of those admitted, with AST and ALT typically below one thousand and the ALT often higher, a modest rise in alkaline phosphatase, and a bilirubin up to four, mostly unconjugated. The abnormalities resolve with hydration and the end of vomiting, which shows they come from dehydration and starvation rather than primary liver disease, and separates them from cholestasis of pregnancy and viral hepatitis, where transaminases reflect ongoing injury. So her vomiting is treated and her liver tests are rechecked after rehydration, with another cause sought if they don't fall.

5:57If they didn't fall, or new right upper quadrant pain appeared, imaging would follow, chosen for fetal safety. Ultrasound is first-line in every trimester, because it uses no radiation or contrast and images the liver, gallbladder, bile ducts, and pancreas well, and Doppler is acceptable when needed, with exposure kept short because acoustic energy can theoretically heat tissue. Magnetic resonance imaging, MRI, without gadolinium is acceptable in all trimesters and preferred over computed tomography, CT. Gadolinium is avoided because it crosses the placenta and lingers in the fetal urine and amniotic fluid, where free gadolinium may dissociate from its chelate.

6:39CT is done only when clinically necessary, with lead shielding of the pelvis and lower abdomen. The acceptable cumulative fetal radiation dose is below fifty milligray, and one CT of the abdomen and pelvis delivers about twenty-five, well under the threshold but adding up across studies. Radiation risk depends on timing: the risk of malformation is highest during organogenesis, before eight weeks, the risk of intellectual deficit dominates from eight to twenty-five weeks, and risk is minimal after twenty-five.

7:11Procedures in pregnancy follow the same reasoning. Cholecystectomy is safest laparoscopically in the second trimester, when organogenesis is complete and the uterus doesn't yet crowd the field. Unsedated flexible sigmoidoscopy is safe, and colonoscopy with anesthesia and fetal monitoring is reserved for indications that can't wait until after delivery, ideally in the second trimester. Elastography isn't validated in pregnancy, because pregnancy changes liver stiffness and gives false fibrosis readings.

7:39Her treatment steps up in order, each step acting on a different nausea pathway. First-line is pyridoxine, vitamin B6, ten to twenty-five milligrams three to four times daily, often with doxylamine, twelve and a half milligrams three to four times daily or at bedtime. A Food and Drug Administration, FDA, approved tablet combines pyridoxine ten milligrams and doxylamine ten milligrams, taken up to four a day. Pyridoxine has a long safety record and minimal placental transfer, and doxylamine, an H1 antihistamine, dampens input from the vestibular system and the chemoreceptor trigger zone.

8:18Second-line is ondansetron, four to eight milligrams every eight hours, or a dopamine antagonist: metoclopramide, prochlorperazine, or promethazine. Ondansetron blocks serotonin type three receptors in the chemoreceptor trigger zone. An old FDA signal of first-trimester cardiac defects has been largely reassured by later meta-analyses, so it's widely used with informed consent, and a small residual cleft palate signal is mentioned in counseling. Metoclopramide blocks D2 receptors and adds a prokinetic effect. Dehydrated, ketotic, and hypokalemic, she's beyond tablets alone, so she gets ondansetron after counseling, plus intravenous fluids.

8:59Her intravenous fluids start with thiamine, given before or with any glucose. Weeks of vomiting deplete thiamine, the cofactor for transketolase and pyruvate dehydrogenase. A glucose load in a thiamine-depleted patient drives glycolysis while pyruvate can't enter the tricarboxylic acid cycle, so adenosine triphosphate, ATP, production fails in thalamic and mammillary neurons, and glucose alone can precipitate Wernicke encephalopathy. So she gets thiamine one hundred milligrams before or with her glucose-containing fluids, the same refeeding rule as in chapter thirty-two.

9:34If her vomiting proves refractory, treatment moves to corticosteroids, methylprednisolone, typically sixteen milligrams every eight hours for two to three days, then a taper, and as a last resort, parenteral nutrition. Steroids are held until after ten weeks because of a possible cleft palate signal with first-trimester exposure, and both steroids and parenteral nutrition wait until first- and second-line therapy has clearly failed. Still vomiting at eleven weeks despite ondansetron and fluids, she'd be eligible for methylprednisolone. At nine weeks, she isn't.

10:09Here are the traps the boards set in these patients. Calling a creatinine of one point zero normal in pregnancy. Attributing a raised ALT to pregnancy itself. Worrying about an isolated rise in alkaline phosphatase. Calling palmar erythema a sign of cirrhosis in pregnancy. Choosing CT before ultrasound, or MRI with gadolinium. Missing the five percent weight-loss threshold for hyperemesis. Calling the liver tests of hyperemesis primary liver disease. Giving glucose before thiamine. And starting steroids before ten weeks.

10:44So, start to finish. Pregnancy labs are read against pregnancy norms. Alkaline phosphatase and alpha-fetoprotein rise, albumin and hemoglobin fall by dilution, and creatinine falls, so one point zero is abnormal. AST, ALT, and GGT don't rise in normal pregnancy, so any elevation needs a cause, most often gallstones, preeclampsia or HELLP, or cholestasis of pregnancy. Imaging starts with ultrasound and moves to MRI without gadolinium, with CT acceptable when needed, well under fifty milligray. Palmar erythema and spider angiomas can be normal.

11:25Hyperemesis gravidarum is persistent vomiting with more than five percent weight loss, ketonuria, and electrolyte change, and its transaminases, usually under one thousand, normalize with hydration. It's treated in steps: pyridoxine with doxylamine, then ondansetron or a dopamine antagonist, then intravenous fluids with thiamine before glucose, and steroids after ten weeks only for refractory disease.

11:49Episode two is reflux, ulcers, and gallstones in pregnancy.

11:53For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of six of chapter thirty-five, and I'll see you in the next one.