Active Learning: Embryology PDF

Active Learning: Embryology James Proffitt PhD...

Active Learning: Embryology James Proffitt PhD [email protected] Foetus in placenta in utero.. Credit: Science Museum, London. Attribution 4.0 International (CC BY 4.0)  Objectives for Today By the end of this session you will be able to: 1. Evaluate the relative impact of teratogen exposure/congenital infection at different stages in development. 2. Evaluate which germ layers are involved in each clinical scenario. 3. Infer which anatomical structures may be impacted by injury to a particular germ layer. 4. Differentiate between different types of twinning based on timing of division and morphology. 5. Apply material from previous sessions to a given clinical scenario.  Question 1 A 30-year-old woman visits your family practice reporting headache, fever, and severe rash. She is especially concerned because she and her partner have been trying to have a baby for some time and she missed her period 1 week ago. Blood test reveals hcG levels consistent with pregnancy, as well as Rubella infection. Which defect is at the highest risk for development in her infant? a. Accessory nipple b. Cardiac septal defect c. Minor deformation of the ear. d. Spontaneous abortion e. Syndactyly (fused digits)  Question 1 Review A 30-year-old woman visits your family practice reporting headache, fever, and severe rash. She is especially concerned because she and her partner have been trying to have a baby for some time and she missed her period 1 week ago. Blood test reveals hcG levels consistent with pregnancy, as well as Rubella infection. Which defect is at the highest risk for development in her infant? a. Accessory nipple Minor epithelial defect-nipples begin forming in week 7 b. Cardiac septal defect Best answer-teratogen exposure in week 3-5 dangerous for major organ development c. Minor deformation of the ear. Minor defects occur later in development (weeks 8 onward)-deformation is mechanically caused d. Spontaneous abortion Weeks 1-2 at highest risk for this (“all or nothing”); patient is well past that point e. Syndactyly in the foot (fused toes) A minor defect that would occur later in development (around 8 weeks), lower limb slightly lags upper limb  Question 1 Review Moore et al., 2020. The Developing Human, Fig. 20.1  Question 2 You see a 40-year-old female patient reporting lower abdominal pain and intermittent vaginal bleeding. Your patient reports that she often experiences cramps, but it has been approximately 4 weeks since her last normal period. A blood test reveals high levels of the hormone hCG consistent with pregnancy, and physical examination shows that the uterus is the source of the bleeding. 2 days later, hCG levels are nearly same (should increase in a healthy pregnancy) and transvaginal ultrasound shows an empty uterus. What is the most likely condition in this patient? a. Abdominal Ectopic Pregnancy b. Complete Pregnancy Loss (Miscarriage) c. Endometrial Polyp d. Tubal Ectopic Pregnancy e. Uterine Fibroids  Question 2 Review You see a 40-year-old female patient reporting lower abdominal pain and intermittent vaginal bleeding. Your patient reports that she often experiences cramps, but it has been approximately 4 weeks since her last normal period. A blood test reveals high levels of the hormone hCG consistent with pregnancy, and physical examination shows that the uterus is the source of the bleeding. 2 days later, hCG levels are nearly same (should increase in a healthy pregnancy) and transvaginal ultrasound shows an empty uterus. What is the most likely condition in this patient? a. Abdominal Ectopic Pregnancy Similar to tubal ectopic pregnancy but much rarer (~1% of ectopic implantations) b. Complete Pregnancy Loss (Miscarriage) Consistent with bleeding, pain, ultrasound and hCG levels, but hCG levels often decrease c. Endometrial Polyp Common cause of abnormal vaginal bleeding but likely visible on ultrasound. d. Tubal Ectopic Pregnancy Bleeding, pain, high hCG levels with abnormal change, and empty uterus indicate possible ectopic pregnancy. Most common site of ectopic implantation e. Uterine Fibroids Large fibroids can cause bleeding/pain-visible on ultrasound and palpable if large  Question 2 Review Sadler, 2019. Langman’s Medical Embryology, Fig. 3.11. Wolters Kluwer Hoffman et al. Williams Gynecology 4th edition, 2020 McGraw-Hill Education  Question 3 A 15-year-old male patient visits your maxillofacial surgery practice to discuss alleviating some problems he’s been having with eating and breathing. You note that his facial bones are reduced in size and his lower jaw is recessed. Examination reveals normal findings otherwise. What other findings would you expect in this patient? a. Hearing difficulties b. Hypocalcemia c. Malformed nails, wispy hair d. Pegged Teeth e. Syndactyly Posnick et al., 2018. Oral & Maxillofacial Surgery, Fig. 40-1A,C  Question 3 Review A 15-year-old male patient visits your maxillofacial surgery practice to discuss alleviating some problems he’s been having with eating and breathing. You note that his facial bones are reduced in size and his lower jaw is recessed. Examination reveals normal findings otherwise. What other findings would you expect in this patient? a. Hearing difficulties Best answer-Treacher Collins due to lack of division in neural crest cells (NCC). Ear ossicles are derived from NCC alongside other facial bones. NCC disorders often come with hearing loss. b. Hypocalcemia Linked to NCC migration issues in diseases like DiGeorge-due to induction interactions between NCC and endoderm to form parathyroid glands that manage calcium metabolism. We are dealing with a syndrome with field defects, not a migration issue (e.g., no problems in heart, gut, etc.). c. Malformed nails, wispy hair An ectodermal disorder but linked to surface ectoderm, not the NCC d. Pegged Teeth An ectodermal disorder but linked to surface ectoderm, not the NCC e. Syndactyly Lack of apoptosis-requires enough cells to begin with and failed cell death. In this case we are dealing with hypoplasia of normal tissues = not enough cell division  Question 3 Review Facial Skeleton from Arch NCC Posnick et al., 2018. Oral & Maxillofacial Surgery, Fig. 40-1A,C Sadler, 2019. Langman’s Medical Embryology, Fig.17.1 Schoenwolf et al., 2021. Larsen’s uman Embryology, Fig. 4.24  Question 4 You see a patient for a prenatal check-up of her twin pregnancy at 10 weeks past her first missed period. Ultrasound examination reveals that the twins share their chorionic sacs but not their amniotic sacs (monochorionic diamnionic). What developmental condition would be of the greatest concern for the health of the developing twins? a. Atrial septal defect b. Conjoining c. Dextrocardia d. Strangulation of the umbilical cords due to entanglement e. Unequal distribution of bloodflow to each twin (Twin-Twin transfusion syndrome) Abrahams et al., 2020. Abraham’s & McMinn’s Clinical Atlas of Human Anatomy, Fig.  Question 4 Review You see a patient for a prenatal check-up of her twin pregnancy at 10 weeks past her first missed period. Ultrasound examination reveals that the twins share their chorionic sacs but not their amniotic sacs (monochorionic diamnionic). What developmental condition would be of the greatest concern for the health of the developing twins? a. Atrial septal defect This condition would not be relevant to twinning alone-would be an intrinsic or extrinsic trigger (e.g., mutation, teratogen exposure) b. Conjoining A risk for monoamnionic twins separating after blastula stage c. Dextrocardia Like with ASD, would not be caused by twinning alone. d. Strangulation of the umbilical cords due to entanglement A risk for monoamnionic twins separating after blastula stage e. Unequal distribution of bloodflow to each twin (Twin-Twin transfusion syndrome) Best answer out of these-shared blood supply puts twins at risk of unequal bloodflow.  Question 4 Review Cunningham et al. Williams Obstetrics 25th edition, 2020 McGraw-Hill Education  Question 5 You see a 30-year-old patient for a pre-natal check up. She is approximately 26 weeks into her pregnancy. She reports a recent increase in her edema and displays high blood pressure. You recall that on your first visit she reported that she is diabetic. Urine tests reveal high levels of protein in the urine, and you suspect early-onset pre-eclampsia (insufficient development of maternal placental arteries). Which embryological structure is most likely to be involved in the development of this condition? a. Epiblast b. Amnion c. Syncytiotrophoblast d. Hypoblast e. Yolk Sac  Question 5 Review You see a 30-year-old patient for a pre-natal check up. She is approximately 28 weeks into her pregnancy. She reports a recent increase in her edema and displays high blood pressure. You recall that on your first visit she reported that she is diabetic. Urine tests reveal high levels of protein in the urine, and you suspect early-onset pre-eclampsia (insufficient development of maternal placental arteries). Which embryological structure is most likely to be involved in the development of this condition? a. Epiblast The epiblast layer forms the embryo itself and is deep to the trophoblast b. Amnion The amnion protects the developing embryo and is deep to the trophoblast c. Syncytiotrophoblast The syncytiotrophoblast layer is the outer layer of the trophoblast, forming part of the embryonic contribution to the placenta. This layer directly interacts w/ maternal spiral arteries and is thought to play a role in early-onset preeclampsia (area of active research) d. Hypoblast The hypoblast layer forms the yolk sac and is deep to the trophoblast e. Yolk Sac The primary yolk sac is involved in development of the chorion, but the more proximate problem is maternal vessels interfacing with fetal tissue, which is due to outer trophoblast derivatives.  Question 5 Review Spiral Artery Week 3 Week 2 Lacunae Chorion Maternal Artery Cytotrophoblast in Decidua Syncytiotrophoblast Shoenwolf et al., 2015 Larsen’s Human Embryology, Fig. 2-2, Elsevier Sadler, 2019. Langman’s Medical Embryology, Fig. 8.7. Wolters Kluwer 5-minute Break Time! Gila Monster (Heloderma suspectum)  Question 6 Which germ layer contributes to the layer between the arrows? a. Ectoderm (Surface) b. Endoderm c. Intermediate Mesoderm d. Somatic Lateral Plate Mesoderm e. Visceral Lateral Plate Mesoderm Netter, 2019. Atlas of Human Anatomy, Plate 25 Duodenum  Question 6 Review Which germ layer contributes to the layer between the arrows? a. Ectoderm (Surface) Too external-skin, integument b. Endoderm Lining of gut/organs + glands c. Intermediate Mesoderm Kidneys/Urogenital only d. Somatic Lateral Plate Mesoderm Parietal bursa, body wall e. Visceral Lateral Plate Mesoderm Best answer-forms supporting structure of the gut tube and endodermal organs (e.g. muscle, submucosal connective tissue) Netter, 2019. Atlas of Human Anatomy, Plate 25 Duodenum  Question 6 Review Endoderm Epithelium Glands Visceral Mesoderm Lamina propria Submucosal connective tissue Nerves in Enteric Plexus = Neural Crest Smooth Muscle Serosa/Visceral bursal layer Sadler, 2019. Langman’s Medical Embryology, Fig. 7.1  Question 7 A parent brings in their 5-year-old child to your practice due to chronic earaches and respiratory infection. You notice a prominent wheeze while listening to the patient breathe. According to the parent the patient also has an extensive history of runny nose and some mild hearing problems. You perform a chest radiograph to examine the health of the lungs. What feature would you most likely see in the resulting image? a. A tumor in the apex of the lung (Pancoast Tumor) b. Multiple cysts formed by dilation of bronchi c. Larger than normal air bubbles in the superior stomach inferior to the diaphragm. d. Dextrocardia (heart pointed to the right) e. A hiatal hernia (stomach herniated into thorax superior to the diaphragm)  Question 7 Review A parent brings in their 5-year-old child to your practice due to chronic earaches and respiratory infection. You notice a prominent wheeze while listening to the patient breathe. According to the parent the patient also has an extensive history of runny nose and some mild hearing problems. You perform a chest radiograph to examine the health of the lungs. What feature would you most likely see in the resulting image? a. A tumor in the apex of the lung (Pancoast Tumor) Apex tumors start w/ neurological symptoms, respiratory once advanced, patient is a child b. Multiple cysts formed by dilation of bronchi Congenital cysts can cause pneumonia from poor drainage, ~1/3 diagnosed in childhood c. Larger than normal air bubbles in the superior stomach inferior to the diaphragm. Tracheoesophageal fistula could introduce more air to gut-not very visible in Xray alone d. Dextrocardia (heart pointed to the right) Situs inversus often co-occurs with respiratory and ear problems due to ciliary dyskinesia (Kartegener syndrome)- links back to role of primitive node cilia in laterality e. A hiatal hernia (stomach herniated into thorax superior to the diaphragm) Severe hiatal hernia can cause pneumonia due to increased reflux, but not ear issues  Question 7 Review Primitive Streak/Node = Organizer, Site of Gastrulation Precursors to all 3 germ layers present -> Teratomas Mouse Embryo, Ventral View Situs Inversus Totalis Sadler, 2019. Langman’s Medical Embryology, Fig. 5.1B. Wolters Kluwer. Schoenwolf et al., 2015, Larsen’s Human Embryology, Fig. 3-5, Elsevier Case courtesy of Dr Maulik S Patel, Radiopaedia.org. From the case rID: 32958  Question 8 You see a neonatal patient that is showing respiratory distress and is having trouble feeding. Attempt to pass a catheter into the stomach fails, indicating a possible tracheoesophageal fistula and esophageal atresia. The infant’s upper limbs and hands are also under-developed. Which condition would you expect to also find in this patient? a. Cardiac ventricular septal defect b. Gut malrotation with volvulus c. Jaw deformation d. Piebald pigmentation e. Under-developed facial bones Case courtesy of Dr Naim Qaqish, Radiopaedia.org, rID: 73686  Question 8 Review You see a neonatal patient that is showing respiratory distress and is having trouble feeding. Attempt to pass a catheter into the stomach fails, indicating a possible tracheoesophageal fistula and esophageal atresia. The infant’s upper limbs and hands are also under-developed. Which condition would be most likely to also be observed in this patient? a. Cardiac ventricular septal defect Best answer-findings indicate mesoderm issues, heart formed by visceral lateral plate mesoderm b. Gut malrotation with volvulus Fits with trouble feeding but not with other findings. Malrotation with gut twisting would cause vomiting, other issues with the intestines (e.g., vascular accident followed by stenosis or necrosis). c. Jaw deformation Would impact feeding, but the jaws are neural crest cell (NCC) derived, inconsistent with limb findings d. Piebald pigmentation TE fistula can come with neural crest cell (NCC) problems due to induction interactions between NCC and endoderm/mesoderm, but inconsistent with other findings. e. Under-developed facial bones Same as pigmentation disorder-would result from NCC problems, but not indicated here.  Question 8 Review Paraxial Mesoderm Intermediate Mesoderm Notochord Vertebral defect Anal atresia Cardiac defect Lateral Plate Mesoderm Tracheo- (Somatic) Esophageal Fistula Lateral Plate Mesoderm (Visceral) Renal defect Limb defect Sadler, 2019. Langman’s Medical Embryology, Fig. 7.1 Raam et al., 2011. European Journal of Medical Genetics, Fig. 1. Elsevier  Question 9 You see a 55-year-old female patient reporting changes to the texture of the skin of the left breast, including skin irritation, breast pain, and a lump in the axilla (armpit). Mammography reveals a tumor; biopsy and Estrogen receptor testing is consistent with lobular carcinoma of the mammary gland tissue. Biopsy of the axillary lymph nodes reveals the tumor has metastasized to nearby lymphatics. What of the following mechanisms is most likely involved in the metastasis of this tumor to the lymph nodes? a. Decreased transition of cells from epithelium to mesenchyme b. Decreased functionality of the adhesion molecule that keeps the epithelial cells of the mammary glands together (E-cadherin) c. Increased apoptosis d. Increased functionality of the adhesion molecule neural cadherin (N-cadherin) that keeps nervous system cells together e. Increased expression of the nervous system adhesion molecule NCAM  Question 9 Review You see a 55-year-old female patient reporting changes to the texture of the skin of the left breast, including skin irritation. Mammography reveals a lesion-biopsy and Estrogen receptor testing is consistent with lobular carcinoma of the mammary glands. What is the most likely mechanism involved in the development of this tumor? a. Decreased transition of cells from epithelium to mesenchyme Transition from epithelium to mesenchyme (undifferentiated connective tissue) is part of the process that allows cancer cells to change behavior and migrate, decrease in this would keep cancer cells in place b. Decreased functionality of the adhesion molecule that keeps the epithelial cells of the mammary glands together (E-cadherin) Best answer-the tumor has broken free from it’s surrounding environment to move into the lymphatic system; loss of function of tissue specific adhesion molecules can allow the tumor cells to migrate c. Increased apoptosis Increased cell death would help keep the tumor under control d. Increased functionality of the adhesion molecule neural cadherin (N-cadherin) that keeps nervous system cells together Adhesion molecules would help keep the tumor in place-adhesion molecules are specific (this one is for nervous system tissue) e. Increased expression of the neural adhesion molecule NCAM Same as above-if cells are sticky it’s harder to move around  Question 9 Review Cell-cell Communication Differential Gene Expression Change in Cell Behavior (e.g., division, Guides Development, differentiation, migration, Can Regulate Cancer Salt et al., 2019, Medical Biochemistry, Fig. 25.1, Elsevier apoptosis)  Question 10 You see a 65-year-old male patient presenting with persistent cough, fatigue, and chest pain. Imaging and subsequent biopsy indicate cancer of the epithelium of the tagged structure. From which germ layer do these cancerous cells originate? a. Ectoderm b. Endoderm c. Paraxial Mesoderm d. Somatic lateral plate mesoderm e. Visceral lateral plate mesoderm Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org, rID: 8095  Question 10 Review You see a 65-year-old male patient presenting with persistent cough, fatigue, and chest pain. Imaging and subsequent biopsy indicate cancer of the epithelium of the tagged structure. From which germ layer do these cancerous cells originate? a. Ectoderm More involved in periphery and CNS (excepting neural crest). b. Endoderm Best answer-lung tissue from outpocketing of gut c. Paraxial Mesoderm Ribs, vertebrae, limb skeleton d. Somatic lateral plate mesoderm Parietal pleura of lungs, but otherwise uninvolved e. Visceral lateral plate mesoderm Lung vasculature, cartilage supporting bronchi, serosa of lung, not main respiratory tissue.  Question 10 Review Thorax Pharynx Transverse CT Lung Buds Heart Gut Tube Connecting Stalk + Vitelline Duct Liver, + Allantois Gallbladder, Pancreas Cloaca Lungs Week 4, Sagittal view Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org, rID: 8095 Sadler, 2019. Langman’s Medical Embryology, Fig. 15.5A. Wolters Kluwer  Thank You! For questions, email me at: [email protected] Give me feedback on this session by scanning the QR code or following the Qualtrics link: https://uarizona.co1.qualtrics.com/jfe/form/SV_6FlEHtfSxMs7OUC Vermillion Flycatcher (Pyrocephalus obscurus)