Pathology Flashcards
. Human placenta is considered which of the following types:
A. Diffuse, epitheliochorial
B. Discoid, hemochorial
C. Cotyledonary, epitheliochorial
D. Zonary, endotheliochorial
A.
The placentas of all eutherian mammals have common structure and function, but there are striking differences among species. Two characteristics that differentiate placental types are: The gross shape of the placenta and the distribution of contact sites between fetal membranes and endometrium and the number of layers of tissue between maternal and fetal vascular systems. Diffuse: Almost the entire surface of the allantochorion is involved in formation of the placenta. (Seen in horses and pigs). Cotyledonary: The fetal portions of this type of placenta are called cotyledons, the maternal contact sites (caruncles), and the cotyledon-caruncle complex a placentome. (This is observed in ruminants). Zonary: The placenta takes the form of a complete or incomplete band of tissue surrounding the fetus. (Seen in carnivores like dogs and cats, seals, bears, and elephants). Discoid: A single placenta is formed and is discoid in shape. (Seen in primates and rodents). Prior to formation of the placenta, there are six layers of tissue separating maternal and fetal blood. There are three layers of fetal extraembryonic membranes in the chorioallantoic placenta of all mammals, all of which are components of the mature placenta: Endothelium lining allantoic capillaries, Connective tissue in the form of chorioallantoic mesoderm, and chorionic epithelium, the outermost layer of fetal membranes derived from trophoblast. There are also three layers on the maternal side, but the number of these layers which are retained - that is, not destroyed in the process of placentation - varies greatly among species. The three potential maternal layers in a placenta are: Endothelium lining endometrial blood vessels, Connective tissue of the endometrium, and Endometrial epithelial cells. In humans, fetal chorionic epithelium is bathed in maternal blood because chorionic villi have eroded through maternal endothelium. Therefore, humans have discoid, hemochorial placenta.
All of the following are true of decidual Natural Killer Cells (dNK) except:
A. dNK represent 20% of the cells in the human decidua
B. Despite their close contact with trophoblastic cells, they do not exert cytolytic function against these cells
C. Histologically dNK cells show up with CD4 immunohistochemical staining
D. Whereas NK cells in the peripheral circulation are inert and require activation to kill target cells, dNK are already activated within the decidua
A.
Natural killer cells have a major regulatory role in implantation and pregnancy. dNK represent 40% of the cells in the human decidua, not 20%, therefore that is the most appropriate answer. Most of these are CD56bright. Where as NK in the peripheral blood require activation to target and kill cells, dNK likely exist in an already activated state within the decidua.
A G2P1001 presents for anatomy scan at 19 weeks gestation. Anatomy is normal. A transvaginal ultrasound is done to check the cervical length. The sonographer notes a low lying placenta and fetal vessels covering the os. Which of the following is not a risk factor for vasa previa?
A. Velamentous cord insertion
B. Umbilical cord cyst
C. Bilobed placenta
D. Low lying placenta
E. Twin gestation
B.
The correct answer is umbilical cord cyst, which is not a risk factor for vasa previa. Vasa previa occurs when unprotected fetal blood vessels run through the amniotic membranes and traverse the cervix. It occurs due to the presence of several risk factors. One major risk factor is when placenta cord insertion is velamentous. Vasa previa may also occur due to the presence of a bilobed or succenturiate placenta, with the connecting vessels similarly overlying the cervix. Moreover, other risk factors include a low-lying placenta observed in the second trimester, multiple gestation, and in vitro fertilization.
A G2P1001 presents with known vasa previa, referred for maternal fetal medicine consultation. She wants to know what the delivery/management plan will be. The best management planfor vasa previa is:
A. Hospitalization at 30-34 weeks, betamethasone at 28-32 weeks and delivery at 35 weeks.
B. Hospitalization at 24 weeks, betamethasone at 28-30 weeks and delivery at 32 weeks.
C. Outpatient management and delivery at 34-35 weeks after amniocentesis ot confirm fetal lung maturity.
D. Hospitalization at time of diagnosis, betamethasone at 24-26 weeks and delivery at 30-32 weeks.
E. Hospitalization at 28-30 weeks, betamethasone at 32-34 weeks and delivery at 34 weeks.
A.
The correct answer is: hospitalization at 30-34 weeks, betamethasone at 28-32 weeks and delivery at 35 weeks. There is no uniformity of opinion as to the optimal management strategy for pregnancies with a prenatally diagnosed vasa previa, particularly in regard to the timing of elective delivery. The Society of Obstetricians and Gynecologists of Canada has published a guideline for management and The Society for Maternal-Fetal Medicine has also published a guideline. Given the risk-benefit profile of antenatal corticosteroids, if indications do not develop earlier, it is reasonable to consider treatment at 28-32 weeks of gestation in case of need for urgent preterm delivery. Antenatal hospitalization has also been proposed, beginning at 30-34 weeks of gestation as many women will require hospitalization for a complication. Hospitalization allows for close surveillance for signs of preterm labor and timely access to cesarean delivery. SMFM recognizes that outpatient vs inpatient management data is limited and thus recommends that this decision be individualized. Delivery timing is controversial. In the largest retrospective series, fetuses who were diagnosed prenatally had a 97% survival rate, and the mean gestational age at delivery was 34.9 2.5 weeks of gestation. Delivery at this gestational age is based on the 10% risk of membrane rupture before labor and the high associated fetal mortality rate. A decision analysis comparing 11 strategies for delivery timing concluded that delivery at 34 to 35 weeks best balanced the risk of prematurity with the risk of neonatal mortality; in this study no benefit was found with management beyond 37 weeks.
Which of the following does not express MHC Class I molecules?
A. Decidua
B. Syncytiotrophoblast
C. Stroma
D. Myometrium
B.
MHC class I antigens (also known as HLA) are expressed on the surface of most nucleated cells in the human body. However, MHC class I and II cells have not been detected on the syncytiotrophoblast cells. However, there is evidence that these Class I cells are present on extravillous trophoblast (EVT) cells which invade the uterine decidua. The syncytiotrophoblast cells, that remain in contact with the systemic maternal immune system, remain immunologically neutral. The EVT, that migrates into the maternal decidua, can remain immunologically active.
. Which of the following statements about myometrial differentiation throughout pregnancy is true?
A. Myometrial differentiation occurs in 5 distinct states: Quiescence, proliferation, synthetic, contractile and labor
B. In the proliferative phase, myocyte proliferation is mediated by IGF-1
C. The synthetic phase of myometrial differentiation is regulated by increasing estrogen level in early pregnancy
D. During the labor phase of myometrial differentiation, up-regulation of CAPS is regulated by progesterone withdrawal
B.
Myometrial differentiation occurs in 4 distinct states: Proliferation, synthetic, contractile and labor. In the proliferative phase, myocyte proliferation is mediated by IGF-1, induced by estrogen. The synthetic phase of myometrial differentiation is regulated by progesterone. During this phase there is extensive remodeling of myometrial cells. Growth of myometrium during this phase is due to cell hypertrophy. During the labor phase of myometrial differentiation, up-regulation of CAPs is regulated at the gene transcription level.
All of the following statements about the contractile apparatus of the uterus are true, EXCEPT: ***
A. The thick filaments in the contractile apparatus are made of myosin, while the thin filaments are made of actin
B. Interactions between actin and myosin are regulated by calmodulin
C. Tropomyosin is an intracellular protein the binds the calcium-CaM complex and facilitates its binding to myosin light chain kinase
D. When the myosin filament interacts with actin, ATPase activity in the myosin head is activated.
C.
The uterine contractile apparatus primarily consists of myosin and actin filaments. Myosin has a globular head component that contain actin binding sites as well as sites with ATPase activity. When myosin and actin interact, ATPase activity is activated. The interactions between actin and myosin are regulated through the calcium-calmodulin complex. This complex binds to the myosin light chain kinase, increasing its activity. This allows an increase in myosin ATPase activity. Tropomyosin is a protein that binds to the calcium-calmodulin complex, making it less likely to bind myosin light chain kinase.
All of the following neonatal complications are associated with small for gestational age (actual birth weight <10th percentile for gestational age) EXCEPT:
A. Hypoglycemia
B. Polycythemia
C. Persistent pulmonary hypertension (PPHN)
D. Hypercalcemia
E. Renal insufficiency
D.
Neonates with Fetal Growth Restriction often have HYPOcalcemia from decreased transfer of calcium in-utero secondary to hypophosphatemia induced by chronic hypoxia.
Therefore, the choice HYPERcalcemia is not true. Neonates who were growth restricted in utero exhibit hypoglycemia from poor glycogen stores in liver and muscles. Placental insufficiency is a cause of chronic intra-uterine hypoxia that leads to polycythemia. Abnormal of pulmonary vasculature with thickened tunica media up-to intra-acinar arteries as result of chronic in-utero hypoxia leads to persistant pulmonary hypertension (PPHN). Chronic in-utero hypoxia and perinatal asphyxia leads to renal tubular injury and possibly renal insufficiency. Therefore, all of these answer choices represent possible associations with FGR, and are not the correct response to this question.
Sharma D, Sharma P, Shastri S (2016) Postnatal Complications of Intrauterine Growth Restriction. J Neonatal Biol 5:232. doi: 10.4172/2167- 0897.1000232
Which of the following is true?
A. Serum albumin levels increase in pregnancy
B. Serum gamma globulin levels decrease in pregnancy
C. Serum beta globulin levels decrease in pregnancy
D. Serum alpha globulin levels do not change in pregnancy
B.
The concentration of albumin decreases in pregnancy. The total amount of albumin is apparently unchanged; decreases in concentration are thought to be the result of an increase in plasma volume. Alpha and beta-Globulins also rise during pregnancy. The elevation is significant throughout pregnancy. It is agreed that there is an increase in the total amount of alpha- and beta-globulins. This increase is large in relation to the total amount of protein present. Since albumin concentration decreases and the alpha- and beta-globulin concentrations increase, there is a sharp decline in the albumin/globulin ratio during pregnancy. There is a fall in the concentration of gamma globulin during pregnancy with a return to normal in 6 to 12 weeks. This is apparently a result of a decrease in the concentration of IgG.
. Which of the following is NOT true?
A. Serum haptoglobin levels increase in pregnancy
B. Serum transferrin levels increase in pregnancy
C. Serum fibrinogen levels increase in pregnancy
D. The percentage of thyroxine bound to thyroxine binding globulin is increased in pregnancy
A.
Haptoglobin, an alpha2-globulin which binds hemoglobin, undergoes no variation during pregnancy Transferrin, the iron binding beta-globulin, is increased during pregnancy. The reason for this increase is unclear. Administration of estrogen or progesterone to non-pregnant individuals, in some cases, caused plasma transferrin concentration to increase; therefore, the increase seen in pregnancy was assumed to be a result of increased blood levels of those hormones. An increase in fibrinogen has also been seen during pregnancy especially during the third trimester. The increase in fibrinogen is thought to be in anticipation of the trauma of delivery. In pregnant women, the percentage of thyroxine bound to thyroxine binding globulin increases, while that bound to albumin decreases.
Decrease in plasma albumin concentration is secondary to:
A. Increase in albumin breakdown due to high levels of progesterone
B. Decrease in albumin synthesis due to estrogen or progesterone effects
C. Increase albuminuria
D. Decrease plasma volume
B.
A fall in the concentration of total protein occurs during pregnancy and is secondary to increase in plasma volume. Another mechanism is that the observed decrease in serum albumin during gestation is due to inhibition by estrogen or progesterone of albumin synthesis normally stimulated by sustained hypoalbuminemia; this was supported when estrogen caused decrease in albumin concentration in non- pregnant women.
Among the following binding proteins, which one is not affected by gestation?
A. Transferrin
B. Haptoglobin
C. Thyroxine binding globulin
D. Cortisol binding globulin
B.
During pregnancy, the concentrations of binding proteins in serum generally increased. The exception is haptoglobin (alpha 2-globulin which binds hemoglobin), its concentration does not vary in pregnancy.
Estrogen promotes all the following changes in the myometrium during parturition except:
A. Increased production of PGE2
B. Increased production of the oxytocin receptor
C. Increased production of NO synthetase
D. Increased production in gap junction formation
C.
For most of pregnancy, progesterone decreases the myometrial responsiveness to estrogen, by inhibiting ERα receptors. Near term, functional progesterone withdrawal leads to a loss of suppression of estrogen receptors and subsequent increased myometrial responsiveness to estrogen. Estrogen promotes a series of changes in the myometrium including increased production of Prostaglandin E2 (PGE2) and Prostaglandin F2 (PGF2) with augmented expression of PG receptors, increased expression of oxytocin receptors, as well as increases synthesis of connexin and myometrial gap junctions. Together, these changes can help lead to coordinated uterine contractions.
Throughout pregnancy, progesterone is responsible for stimulating uterine NO synthetase. This is thought to be a major factor in uterine quiescence.
During pregnancy, the enhanced activity of which type of immune cells promotes tolerance of fetal alloantigens?
A. Natural killer cells
B. Macrophages
C. Regulatory T cells
D. Th1 Cells
E. Dendritic cells
C.
Pregnancy is most often considered an “anti-inflammatory” state with a shift in predominance of TH2 cells as compared to TH1 cells. Concurrent with this increase in TH2 responses during normal pregnancy, there is an increase in activity of regulatory T (T-reg) cells. These T-reg cells are responsible for maintaining self-tolerance by suppressing self-reactive lymphocytes. It is hypothesized that T-reg cells synchronize immune tolerance to the fetus at the maternal fetal interface by preventing an immunologic response to the fetal antigens.
Natural killer cells (NK), macrophages, and dendritic cells are all immune cells actively involved during pregnancy, however, their role in maintaining tolerance to the fetus appears to be less clear than T-reg cells. NK cells have been shown to have a key role in remodeling of the decidual spiral arteries. The exact role of macrophages is not clear, but they appear to have a role in implantation, placental development, and cervical ripening. Dendritic cells play a role at maintaining normal cytokine profiles at the maternal fetal interface in relationship to decidualization.
. All of the following are intrinsic “hormonal factors” that can lead to activation of myometrium, except:
A. Oxytocin
B. Prostaglandins
C. Parathyroid hormone related peptide
D. Corticotropin releasing hormone (CRH)
E. Estrogen
C.
Unlike other smooth muscle, myometrial cells have sparse innervation. Myometrial contractility, is therefore, predominantly under control of humoral or intrinsic factors. Circulating levels of oxytocin do not change in pregnancy, however, the oxytocin receptor is significantly upregulated near term. This accounts for increased receptivity to oxytocin. There are increased levels of prostaglandin (PG) production throughout pregnancy, primarily in the amniotic fluid. PGproductions appears to increase the most prior to increased myometrial production of PG and myometrial contractility. This supports the hypothesis that PG are involved prior to the onset of contractions, and are not elevated merely as a cause of contractions.
Activation of the fetal hypothalamic-pituitary-adrenal axis plays a key role in parturition. Activation of the fetal hypothalamic-pituitary-adrenal axis during the latter part of pregnancy results in release of large amounts of fetal cortisol, which in turn increases placental production of CRH. CRH has many roles in pregnancy and parturition, including enhanced prostaglandin production in the amnion, chorion, and decidua, and potentiation of the effects of oxytocin.
Estrogen has not been shown to directly stimulate the myometrium itself. However, it does increase the production of myometrial gap junctions, which are key to uterine action potentials. Parathyroid hormone-related peptide is a smooth muscle relaxant capable of inhibiting oxytocin-induced contractions. It is hypothesized to have a role in uterine quiescence.
