Repro USMLE step 1 9-3 (5) Flashcards
This primigravid patient presents with edema and gestational hypertension (systolic BP >140 and/or diastolic BP > 90 after 20 weeks’ gestation). She likely has preeclampsia, which is defined as new-onset hypertension with proteinuria or signs of end-organ damage after 20 weeks’ gestation. To confirm the diagnosis, the physician would test for?
protein in the urine using a dipstick. (This would rule out possible gestational hypertension and benign edema during pregnancy.) A 24-hour urine collection can also be used to accurately measure protein levels. Proteinuria is defined as a finding of 1+ via urine dipstick or, preferably, excretion of =300 mg of protein during a 24-hour urine collection. The table below summarizes the characteristics of hypertensive disorders seen in pregnancy.
Preeclampsia is caused by abnormal development of the placental spiral arteries. Abnormal placental vasculature leads to placental hypoxia and ischemia, which in turn results in release of inflammatory factors that cause endothelial injury to the maternal circulation. Preeclampsia affects 7% of pregnant women in the third trimester and is more common in patients with pre-existing hypertension, diabetes, chronic renal disease, and autoimmune disorders (eg, presence of anticoagulant and anticardiolipin antibodies). Complications of untreated preeclampsia include?
placental abruption, coagulopathy, renal failure, uteroplacental insufficiency, and eclampsia (defined as signs and symptoms of preeclampsia with seizures) and/or HELLP syndrome. Management of preeclampsia involves administration of antihypertensive agents and intravenous magnesium sulfate (to prevent seizures). Definitive treatment is delivery of the baby.
A peripheral blood smear would help identify schistocytes suggesting hemolysis secondary to HELLP syndrome. HELLP syndrome represents a complication of untreated preeclampsia, a diagnosis that has not been established in this patient.
Urine ketones can be present in diabetic ketoacidosis or starvation states. This patient has been eating a healthy diet and does not have any history of diabetes, making either of these states unlikely.
An EEG can be useful for?
determining seizure activity, which can occur with eclampsia. However, this patient does not have any indication for an EEG.
Serum cortisol level would be useful in determining hypercortisolism, or Cushing syndrome. Although this patient has hypertension and weight gain, she does not have any other symptoms of excess cortisol, such as truncal obesity, abdominal striae, or a buffalo hump
Preeclampsia is defined as onset of hypertension after 20 weeks’ gestation with?
proteinuria or signs of end-organ damage. It is more common in patients with diabetes, chronic renal disease, autoimmune disorders, or preexisting hypertension.
This child’s presentation of intellectual developmental delay, growth retardation, fair skin, eczema, and a musty body odor is most consistent with phenylketonuria (PKU). This is an autosomal recessive condition characterized by the deficiency of phenylalanine hydroxylase, an enzyme that converts phenylalanine to tyrosine. Tyrosine is an important amino acid that is required for the synthesis of dopamine via tyrosine hydroxylase and dihydroxyphenyalanine decarboxylase. With a decreased level of tyrosine in this patient, one can reasonably expect?
a low level of dopamine.
It is worth noting that PKU can also be caused by a deficiency in tetrahydrobiopterin, an important cofactor in the conversion of phenylalanine to tyrosine. Screening for PKU occurs 2–3 days after births that take place in the hospital setting. This patient’s immigrant status suggests that this screening might have been missed. Because patients with PKU can no longer produce tyrosine on their own, treatment includes supplementing the diet with tyrosine and tetrahydrobiopterin with the goal of increasing the available precursors for dopamine synthesis. Phenylalanine also must be eliminated from the diet.
Low levels of cysteine and methionine both contribute to homocystinuria, a disease characterized by osteoporosis, marfanoid habitus, kyphosis, lens subluxation, and atherosclerosis.
Low levels of ?-aminobutyric acid (GABA) are seen in rare disorders of?
GABA synthesis and are characterized by widespread neurocognitive deficits and seizures.
A low level of an essential amino acid, such as phenylalanine, would only be observed in periods of rapid growth or poor diet.
PKU is a disorder caused by either a deficiency in phenylalanine hydroxylase or tetrahydrobiopterin. The enzyme phenylalanine hydroxylase converts phenylalanine to tyrosine. Because tyrosine is required?
for the production of dopamine, if the level of tyrosine is decreased, the level of dopamine will also be low.
This patient presents with hirsutism, weight gain, irregular menstrual cycles, and infertility. These symptoms suggest a diagnosis of polycystic ovarian syndrome (PCOS). PCOS results from hormone derangements (luteinizing hormone hypersecretion is the hallmark of PCOS), which manifest as obesity, hirsutism, oligomenorrhea, and acanthosis nigricans (velvety hyperpigmentation, often around the neck and axillae).
PCOS is often associated with insulin resistance, which leads to?
hyperinsulinemia. PCOS can also cause hyperglycemia and hyperlipidemia. Oral contraceptive pills are often prescribed to reduce the levels of circulating androgens that cause the hirsutism and to help regulate the menstrual cycle. Clomiphene is prescribed for women who desire pregnancy.
Hypermagnesemia can be seen in patients with renal failure. Renal failure presents with decreased urine output, edema, fatigue, shortness of breath, and confusion, which are not symptoms seen in this patient. Hyperuricemia is associated with gout. Patients with gout typically have a history of extremely painful monoarticular arthritis, hyperuricemia, and subcortical bone cysts (tophi), which this patient does not have. Hypothyroidism presents with?
weight gain and menstrual irregularities, but the patient does not have any other symptoms of this condition, such as brittle hair and cold intolerance. Similarly, hypercortisolism, seen in patients with Cushing syndrome, can cause weight gain and menstrual irregularities, but this patient lacks many of the other symptoms, such as moon facies, fat pads, and abdominal striae.
PCOS often presents with obesity, hirsutism, oligomenorrhea, and acanthosis nigricans. Many patients with PCOS have insulin resistance leading to ?
hyperinsulinemia. Treatment of insulin resistance in these patients can be a useful adjuvant to standard management, which includes weight loss and use of oral contraceptives.
This patient is presenting with a molar pregnancy. This condition typically presents with vaginal bleeding, a markedly elevated β-hCG level, and a larger than expected uterus. (At 6-weeks gestational age, the uterine fundus should not be palpable outside the pelvis.) The key to answering this question is that the mole is 46,XX, making it a complete mole, which is exclusively the product of ?
paternal DNA. The majority of complete moles arise when an egg has no chromosomes as a result of meiotic error, the empty egg is fertilized by a normal X-bearing sperm, and the 23 paternally-derived chromosomes duplicate to produce a 46,XX karyotype. In 2% of cases, complete moles progress to frank choriocarcinoma. In some cases, the markedly elevated β-hCG levels give rise to symptoms of hyperthyroidism because of a shared subunit. The red arrows in the histologic sample on the left below highlight edematous molar villi characteristic of a hydatidiform molar pregnancy. Compare these edematous villi to the well-developed vascular villi highlighted by the green arrows in the figure on the right, which are associated with normal pregnancy.
There is no molar pregnancy generated exclusively from maternal DNA.
Partial moles contain both?
maternal and paternal DNA. Partial moles most often arise from the fertilization of a normal egg by two normal sperm, thus containing both maternal and paternal DNA. As such, karyotype
analysis of a partial mole would reveal either 69,XXX, 69,XXY, or 69,XYY. Of note, the β-hCG level is far less elevated in partial mole, and the risk of progression to choriocarcinoma is much lower.
Although viruses can contribute to some cancers (eg, African Burkitt lymphoma), there is no evidence supporting a role in hydatidiform mole formation.
There is no known role of viral RNA in complete mole formation.
This postmenopausal woman’s new-onset vaginal bleeding should raise suspicion for endometrial hyperplasia influenced by?
pathologic unopposed estrogen secretion by ovarian cells. The thickened endometrial stripe seen on this patient’s ultrasound provides more evidence of hyperplasia or carcinoma.
Hyperestrogenism should be suspected in elderly women with postmenopausal bleeding and/or cystic breasts and in young patients with precocious puberty. It is important to keep this pathophysiology in mind, as estrogen-secreting tumors lead to endometrial carcinoma in 15% of patients. In this case, the underlying cause is a granulosa cell tumor of the ovary. The classic histologic finding in such tumors is the presence of Call-Exner bodies (see circles in image below), which are follicles composed of granulosa cells haphazardly arranged around a space which may contain eosinophilic secretions.
A cystic collection of thyroid, bone, and neural tissue refers to a mature teratoma. Teratomas contain tissue derived from at least two different embryonic layers (for example cartilage, gastrointestinal epithelium, and adipose tissue); one would not expect to see Call-Exner bodies or vaginal bleeding with a teratoma. Epithelial cells resembling fallopian-tube lining with concentric calcifications describes a serous borderline tumor (or serous cystadenoma). Instead of Call-Exner bodies, one would see a tumor lined with epithelium resembling that of the fallopian tube and psammoma bodies (concentric rings of calcification). Because they do not secrete estrogen, they do not classically present with?
vaginal bleeding and would not cause a thickened endometrial stripe. An ovarian endometrioid carcinoma has estrogen-sensitive ovarian cells that resemble malignant endometrial tissue. Although they may resemble endometrial tissue, the cells are usually estrogen sensitive (as opposed to estrogen secreting); Call-Exner bodies are absent; and the patient would not present with vaginal bleeding. Krukenberg tumors are composed of mucin-secreting signet-ring cells, usually of gastric origin; however, they may be from other sites. The classic histologic finding is a mucin-secreting signet-ring cell.
Granulosa cell tumors of the ovary are?
estrogen-secreting tumors that typically present in postmenopausal women with abnormal vaginal bleeding, a thickened endometrial stripe, and a pelvic mass on ultrasound. Call-Exner bodies are classically found on histologic examination of the tumor.
