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Tracy Woolton Made by Natalja Woloncewicz – Year 3 Phase 1 and 2 lead Paediatric Society Natalja.Woloncewicz@student.Manchest er.ac.uk – any questions on this case, other cases or Years 1 and 2, feel free to email me J Case 1, Sem 1 – Menstruation and Foetal Development Key Words of the Case – make sure you can describe what each are and their relevance. • Uterus • Granulosa proliferation • Perimenopause • Embryo • Fallopian tubes • Primordial follicles • Eumenorrhea • Ampulla • Stratum functionalis • Primary follicle • Anovulation • Isthmus • Stratum basalis • 2-cell-2-gnadotrophin model • Dysmenorrhea • Fallopian tube • Spiral arteries • Aromatase • Syncytiotrophoblast's • Infundibulum • Menstruation • 17-beta-oestradiol • Stigma • Corona radiata • Follicular phase • Follicular atresia • Polyspermy • Placenta • Ovulation • Luteinization • Macula pellucida • Blastula • Luteal phase • Oocytes • Theca externa • Blastocyte • Progesterone • Menarche • Proteolytic enzymes • Acrosome • Menses • Menopause • Steroid hormones • Zona pellucida • Endometrium • Fertilisation • Combined pill • Acrosin • Anterior pituitary gland • Folliculogenesis • Progesterone only pill • Cortical reaction • Ovum • Androstenedione • Fertilisation • Pronuclei • Ovary • Relaxin • Cleavage divisions • Zygote • Follicles • Inhibin • hCG • Morula • Oestrogen • Fimbria • Cytotrophoblasts • Blastomere • LH • Ampulla • Blastocyst • Primitive yolk sac • Corpus luteum • hCG • Inter-cellular mass (ICM) • Allantois • Corpus albicans • Plasmin • Trophoblasts • Chorion Key words continued … • Endoderm • Sinus venous • Mesoderm • Bulbus cordis • Ectoderm • Truncus arteriosus • Amnion • Germ cell layers • Caudal end • Amniotic fluid • Cephalic end • Chorion • Primitive streak • Umbilical cord • Organogenesis • Foetal chorionic villi • Neuralisation • Intervillous space • Neural plate • Ovarian reserve • Neural tube • Follicular atresia • Neural groove • Menopause • Neural crest cells • Corpus luteum cysts • Neural pores • Mifepristone • Somite's • Placental clock • Octic placode • Foetal HPA axis • Synocytocin • Optic placode • Limb buds • Ductus arteriosus • Cardiogenic area • Foramen ovale • Cardiogenic cords • Ductus veinous • Endocardial tubes • Primitive heart tube Uterus There are 3 distinct layers of the uterus – endometrium, myometrium, perimetrium. Endo always means inside. Endo = ‘in’do Myo will always mean muscle – ‘m’ for muscle. Peri always means a layer that is enclosing another, or is the outer layer. The endometrium is further divided into 2 layers. - The stratum functionalis and the stratum basalis. • The stratum functionalis is the most outer layer. It is the ‘functional’ layer meaning fertilisation occurs here and it’s the layer that is shed when there is menstruation. Is supplied by the spiral arteries. It makes up 2/3rds of the endometrium. • The stratum basalis is the innermost layer of the endometrium. It is a base so nothing happens to it. It is a constant layer. Is rd supplied by the straight arteries. Makes up 1/3 of the endometrium. Menstruation And Ovarian Cycle Menstruation Follicular Phase Ovulation Luteal Phase Days 1-5 Days 6-12 Days 13-15 Days 15-28 GRAPH IS A HIGH YIELD QUESTION Eumenorrhea – normal periods Anovulation – an absence of ovulation Dysmenorrhea – irregular periods The average menstrual cycle lasts 28 days but can vary between 20 – 35 days. It consists of two cycles – the ovarian cycle and the uterine cycle: 1. The Ovarian cycle – which refers to the development of the follicle and ovulation. 2. Uterine cycle – where the functional endometrium thickens and then sheds in response to ovarian activity. The Ovarian Cycle GO OVER THIS IN YOUR OWN TIME Follicular Phase: 1. GnRH is released from the hypothalamus in the brain by pulsatile secretion. 16. The other unchosen follicles degenerate and break down and this process is 2. The release of GnRH stimulates the release of FSH and LH from the nearby anterior pituitary known as follicular atresia. gland. 17. In ovulation the dominant follicle will release the oocyte out of the ovum. 3. LH and FSH are secreted into the ovum by ovarian capillaries. 18. After ovulation the LH levels drop right back down and so will the levels of 4. The ovaries have lots of primordial follicles, and in each cycle on a few (are 20 follicles) are GnRH. 19. The FSH has a small spike as a side affect of the LH surge. stimulated to mature into primary follicles. 5. The FSH and LH stimulate the maturation of the primary follicles (also know as pre-antral follicles) into secondary follicles (small/ large antral follicles). This happens by the proliferation Luteal Phase: of granulosa cells due to the high levels of FSH being produced. Theca cells form in small layers 1. LH surge stimulates the production of proteolytic enzymes that break down around the granulosa cells. The layer known as the theca internal secretes the androgen the follicle wall, allowing release of the oocyte. 2. After the follicle releases the oocyte from the ovum the remaining follicle hormone and the theca externa layer creates a follicular capsule. consisting of theca and granulosa cells remains in the ovum. The theca and 6. Per the two cell two gonadotrophin model theca cells within the follicle develop LH receptors which bind to the LH causing cholesterol to be converted by enzymes into androstenedione (an granulosa cells are now luteinised and the remaining structure is called the androgen hormone). corpus luteum. This is known as luteinisation. 7. The androstenedione then diffuses into the nearby granulosa cells. 3. The corpus luteum will slowly degrade for roughly 10-12 days. However, the 8. FSH binds to the FSH receptors on the granulosa cells and stimulates the production of the corpus luteum has a very important role : it secretes three major sex hormones – oestrogen, progesterone and inhibin. It will continue to release these three enzyme aromatase. 9. The enzyme aromatase then catalyses the reaction of converting androgen into 17beta hormones until it is broken down by macrophages into a fibrous scar connective oestradiol (a form of oestrogen). tissue known as the corpus albican. 10. Granulosa cells secrete oestradiol out of the follicle in a follicular fluid. 4.The role of inhibin is to inhibit FSH production in a negative feedback loop. 11. In the first 0-10 days negative feed back occurs. The production of the oestrogen from the 5. The inhibition of FSH prevents follicles beginning to mature again before the follicle inhibits the release of LH even though GnRH is being secreted. This is why the level of next menstrual cycle needs to begin. Progesterone inhibits GnRH in another negative feedback loop. the LH will remain constant on a hormone conc graph. 12. At low concs of oestrogen LH is inhibited. However, at high concs of oestrogen LH is 6. After ovulation oestrogen will decrease slowly and progesterone will increase stimulated. slowly. 13. FSH is secreted only a low oestrogen levels, so as the follicle continues to mature, it will 7. Progesterone, oestrogen and inhibin will decrease until the corpus luteum produce more oestrogen the conc of oestrogen will increase and therefore the conc of FSH in fully degrades. the blood will begin to decrease. Menstruation: 14. Oestrogen levels continue to increase over the first 10 days the conc of oestrogen reaches a high level in the blood and positive feedback loop is activated and the oestrogen stops Due to the reduction in the progesterone there is no longer a higher enough inhibiting the LH and instead it causes a surge in the secretion and production of LH. conc to inhibit GnRH and therefore the conc of GnRH begins to increase again, 15. The surge of LH cause the ovulation of the most mature follicle known as the dominant the endometrial lining sheds in the uterus and the new menstrual cycle can follicle in the ovary. begin. The Uterine Cycle Proliferative phase (in the follicular phase of the ovarian cycle ): Average of 1. The maturation of the primary/secondary follicle in the ovarian cycle ­ conc of oestrogen in the blood. 43ml blood on a 2. This causes a few changing in the uterus: menstrual a) Thickening of the endometrial lining. period b) Growth and enlargement of the endometrial glands. c) Stratum basalis undergoes mitosis to produce the functional layer (stratum functionalis) in the uterus. d) Spiral arteries form in the functional layer. e) Oestrogen also affects the cervical mucus consistency – making it more hospitable to spermatozoa (sperm). Secretive/ secretory phase (in the luteal phase in the ovarian cycle): 1. The corpus luteum produces progesterone in the ovarian cycle 2. The progesterone increase the cervical mucus secretion making it thicker and this means it is less hospitable for sperm 3. Spiral arteries in the stratum functionalis lengthen and grow longer. Menstrual phase: 1. Progesterone¯ due to the degredation of the corpus luteum. 2. The progesterone kept the spiral arteries In the functional layer of the endometrial layer dilated so as the progesterone levels decrease, the arteries begin to collapse, this means that the functional layer of the endometrium does not receive and oxygen supply. no oxygenation of the tissue and so it become necrotic tissue and degenerates. Cause of period cramps 3. Blood fills the uterine cavity from the broken/degenerating vessels. This is the shedding of the uterus functional layer of the endometrial layer and is evacuated through the vagina as a menstrual bleed.Menstrual Hormone Summary HORMONES ARE HIGH YIELD QUESTIONS Ovulation Ovulation is the 14th day of a standard 28 day cycle. Oocyte Structure A stigma, also called macula pellucida, refers to the area of the ovarian 1. The cytoplasm of the egg is called ooplasm. surface where the Graafian follicle will burst through during ovulation 2. The zona pellucida has many different roles and release the ovum. including in oocyte development, protection A few days before ovulation the follicle begins to swell. The follicle during growth and transport, fertilization, spermatozoa binding, preventing polyspermy, causes a protrusion against the edge of the ovary. This forms the stigma blastocyst development, and preventing in the ovarian capsule. Theca externa cells of the follicle produce premature implantation (ectopic pregnancy). Proteolytic enzymes (lysosomes) which are activated by progesterone. These enzymes are released and weakens/ ruptures the follicular capsule and causes the release of the oocyte into the fallopian tubes Common question about what changes there and the degredation of the stigma. are to the oocyte to prevent polyspermy. Contraceptive Pill 1. Combined oral contraceptive pill – contains oestrogen and progesterone. Progesterone – supresses GnRH which supresses FSH and LH. Means a follicle cannot develop and there is no LH surge therefore there is no ovulation. It thickens the cervical mucus and alters fallopian tube peristalsis – makes the endometrium hostile to implantation and the cervix reflectively impermeable. The oestrogen suppresses the FSH secretion (negative feedback) which inhibits follicular development. It also increases the number of progesterone receptors. Mifepristone can be used as a form of emergency contraception (morning after pill) or the early termination of a pregnancy. 2. Progesterone only pill – known as the mini pill. May be started straight after delivery and has no effect on lactation, must be taken at the same time every day. Uses of a contraceptive pill - Irregular or absent menstrual, Treatment of menstrual cramps, Acne, PMS, Endometriosis, Primary Ovarian Insufficiency (POI) etc… Foetal Development Overview Fertilisation Implantation Extraembryonic Membrane Production Day 8 Day 11/12 Cleavage Divisions Days 1-3 Blastocyst Formation Gastrulation Days 4-5 Days 14-19 Fertilisation Conception is the name given to the fertilisation of the What is the process of fertilisation? ovum by spermatozoa usually occurring in the ampulla 1. The heads of the sperm known as the acrosome contain or the isthmus of the fallopian tube. digesting enzymes such as hyaluronidase breaks down the bonds between the adjacent follicle cells in the corona radiata In ovulation the infundibulum of the fallopian tube moves over the site (outermost cells of cell). of the ovary where the rupture of the follicle is going to happen and 2. The acrosomal head ruptures when it binds to the second layer where the oocyte is being released. Finger like projections on the end of of the ovum called the zona pellucida and this causes the release the fallopian tubes called fimbriae wrap around the ovary and direct the of an enzyme called acrosin. This is called the acrosomal ovum into the fallopian tube. Peristaltic action of the longitudinal and reaction. circular smooth muscle layers moves the ovum down the fallopian tube. This is aided by the action of the ciliated epithelium lining that waft thecrosin can break down the zona pellucida and therefore the ovum down in a flow. The ampulla is the most common area of sperm is able to access the membrane of the oocyte. fertilisation. 4. The sperm is absorbed into the cytoplasm and this causes calcium ions to be released causing granules in the oocyte to release an enzyme destroying sperm receptors on the membrane surface. This results in the inactivation of sperm receptors, the zona pellucida also hardens to prevent polyspermy which is the fertilisation an oocyte by more than one sperm. 5. The process that causes the zona pellucida to become impenetrable to any other sperm once fertilisation has taken Why are there so many sperm released in ejaculation? The place is called the Cortical Reaction. sperm is much smaller than the ovum. Multiple/dozens of 6. The term used to describe a nucleus of the sperm and the sperm is needed to be able to fertilise and egg, this is because nucleus of the oocyte before they are fused is pronuclei. These the outer layer of the ovum called the corona radiata needs to migrate to the centre where they fuse known as amphimixis be broken down in order for the sperm to fertilise the oocyte. where the zygote with 46 chromosomes is formed. Structure of Oocyte Structure of Sperm 1. Acrosome – contains the enzyme acrosin that breaks down the corona radiata. 2. Lysosomes – Hyaluronidase breaks down the bonds between the cells between the corona 1. Corona Radiata – outer layer radiata 2. Zona Pellucida – inner layer 3. Tail – Flagellum, helps the sperm swim through the uterus/vagina/ mucus 4. Acrosin – breaks down the zona pellucida (inner layer) Days 1-8 Post Fertilisation Cleavage Divisions Days 1-3 Implantation – Day 8 There is a series of cell divisions where the cytoplasm subdivides into Blastocyst - Days 4-5 – Cleavage Implantation usually occurs on day 8 post fertilisation where the other cells is known as cleavage. blastocyst embeds itself into the endometrial lining of the uterus. A blastocyst is created roughly 4-5 days after fertilisation and usually contains 1. Due to the high levels of progesterone maintaining the vascular **It is important to know that the number of cells increases but the about 32-64 cells. and glandular supply of the endometrial layer of the uterus the overall size of the embryo stays the A blastocyst consists of two parts – cells have high concentrations of glycogen and lipids. same. • The ICM = inter cell mass 2. Due to the high levels of glycogen being secreted the blastocyst • The divisions are asynchronous • Trophoblasts enlarges and when it becomes fully formed it interacts with the All together is roughly 12 cells. lining of the uterus (endometrium) and implantation begins. therefore there can be a result of 3. The trophoblast begin to increase rapidly in number and this an odd number of cells. • The first division of the cells THE INTERCELL MASS is a group of cells thickens the trophoblast layer of the blastocyte. usually occurs 30 hours after within the blastocyte which are 4. Cells inside the blastocyte are called cytotrophoblasts and they fertilisation and subsequent pluripotent stem cells and these will go differentiate into cells called syncytiotrophoblast. These are cells onto produce the embryo. that have lost there membrane and consequently the cytoplasm divisions continue to happen have been fused together to make multinucleated cells. These every 10-12 hours. • On day 2 there is usually 4 cells THE TROPHOBLASTS are a lining around cells then secret a hormone called hyaluronidase which is able to and then by day 3 there is 8. the blastocyst. The trophoblast will go break down the stratum functionalis. • On day 3 the morula stage is onto develop the embryonic 5. These syncytiotrophoblast's produce a hormone called hCG reached where the 8 blastomeres components of the placenta and the which is secreted into the ovaries and stimulates the corpus extraembryonic tissues. luteum and prevents it from being degraded so it can maintain the develop into a blastula and then production of progesterone and oestrogen. develop into a blastocyst. 6. The stimulation of the continuation of progesterone causes the uterine wall to become more vascular and more glandular and the endometrium enlarges and secretes more glycogen and lipids for nutrients of the blastocyte which is called the decidual change. 7. The blastocyte burrows itself into the stratus functionalis. 8. The trophoblast continues to form the placenta. Extra Embryonic Membrane Production Embryogenesis – Gastrulation (Germ Layers) By this time the embryo has completely embedded itself into the endometrial stoma and the surface epithelium has fully encapsulated Gastrulation a time period allowing cell movements to get and covered over the hole in the uterus where the embryo embedded tissues and organs into correct orientation and is the process itself. When embedded the embryonic membrane which entirely that establishes the Three Germ Cell Layers: surrounds the embryo makes a cavity filled with amniotic fluid and this is called the amnion. Endoderm – innermost layer – differentiates into lung cells (alveolar cells), thyroid cells, pancreatic cells. 1. The Primitive Yolk Sac is formed – this is the first site of blood cell Mesoderm – middle layer – differentiates into cardiac formation. muscle, skeletal muscle, tubule cells of the kidney, red 2. The Allantois – becomes the vascular connection between the blood cells, smooth muscle in gut embryo and the placenta Ectoderm – outermost layer – differentiates into skin 3. The Chorion – becomes the principle/ main part of the placenta as cells of epidermis, neurons of the brain, and the pigment the pregnancy progresses. cells. 4. The ICM contains pluripotent cells and they can give rise to any other type of cell. This is important for tissue formation as nan Organs derive from the different germ layers. High embryo must form organs of correct size and orientation. Organs Shape change in the embryo allows the organs to get in the yield must contain correct combinations of differentiated cell types. correct orientation for the correct body plan and structure. Prior to gastrulation the embryo is a disc like shape. An invagination occurs in the caudal part of the embryo and this forms a structure called the primitive streak. Cells migrate through the primitive streak and the migration movement gives rise to the mesoderm layer and changes the shape of the embryo. The shape change is very prominent between days 15 -17 and days 17-19. The change in shape causes the nervous system to begin to develop. It produces a cephalic region which will be the future brain and the caudal region. Organogenesis Nervous System (Neuralisation) (covered more in depth in Sem 3) The nervous system development occurs after gastrulation and begins in days 19-21 where neuro tissue arises from the ECTODERM LAYER. The embryo will undergo a process called NEURALISATION which is the neural plate forms the neural tube. It produces a cephalic region which will be the future brain and the caudal region. Neuralisation – the process of making the nervous system in development 1. The lateral edges of the neural plate become elevated to from natural folds and the depressed mid-region forms the neural groove. 2. The neural folds gradually fuse at the mid-region and the neural tube is formed. 3. The neural tube has special types of cells called neural crest cells. 4. The open regions of the neural tube are called neural pores at either end. 5. These neural pores close which signals the end of neuralisation. – at roughly days 23- 26 6. However if these ends do not close they can result in birth defects. For example – failure to close at the cephalic region will result in a defect called exencephaly and closure at the neural tube at the spinal region results in a defect called. spina bifida. 7. Between the caudal end and the cephalic end the closed neural tube along the dorsal region will give rise to the spinal cord – and this contains cells calls neural crest cells. 8. When the neural crest is formed neural cells migrate out of the dorsal neural tube. 9. These cells are incorporated into a number of tissues e.g. neurones and glia of the ANS, glial Schwann cells of the PNS, melanocytes of the skin, and the bone, cartilage, muscles and conn tissue of the face. 10. Structures called SOMITE’S arise alongside the neural tubule. The first pair arise around 19 days post fertilisation. 11. They develop in succession (order) of anterior to posterior. There are 44 pairs in total and they go onto produce muscle, vertebrae and rib bonesHOW DO I REMEMBER WHA T THE CAUDAL SIDE IS AND WHA T THE CEPHALIC SIDE IS? CEPHALIC HAS A ‘H’ IN IT SO IT IS THE SIDE OF THE HEAD Organogenesis Ear Development A question was asked in the Sem Around week 4 visible structures called Ear, Eye, Limb, Respiratory Tract Development 1 exam on the name of the OTIC PLACODES form. They are process of lung development. Limb Development ectodermal thickening visible on the Limbs develop on the embryo from surface. These otic placodes will go onto structures called LIMB BUDS. Lung Development develop the ears. They begin to There are two types – there are forelimb The lungs develop in a process called disappear from the surface at around buds and hindlimb buds and they project BRANCHING MORPHOGENESIS. Even though week 5, forming the inner components the endoderm and mesoderm supply most of of the ears. outwards. Forelimb buds are present first the alveoli the ectoderm supplies neural and as development proceeds we begin innervation and the mesoderm also supplies to see the hindlimb buds form. musculoskeletal support. At week 7 the hands and feet become 1. Weeks 3-7 the embryonic development distinguishable and so do the digits. 2. Weeks 5-17 pseudoglandular Cartilage shows the pre-cursors to digits 3. Weeks 16- 26 canalicular and eventually the cells in the cartilage. 4. Weeks 26 – 36 (birth) saccular Eye Development Apoptosis of the webbing between the Around week 4 structures called the digits allows the separation of the digits 5. Birth – 3yrs alveolar OPTIC PLACODE form on the embryo. forming visible fingers and toes. Cells in the optic placode will form the optic lens and go on to develop the eyes. Organogenesis Heart And Gut Development Heart Development Gut Development – covered again in Sem 4 and very high Yield in Sem 4 Heart development begins around days 22-23 and continues through to week 8. Heartbeats can begin form The GI system arise from the endoderm – the innermost around day 22 of pregnancy. Circulation can begin to layer. And usually arises in week 2-3 of gestation. The function around days 27-28. contribution of other germ layers happens from week 4 1. In the head of the embryo the heart develops from a where the mesoderm contributes mesentery, smooth group of mesodermal cells called the cardiogenic area. muscle and blood vessels and the ectoderm contributes 2. The cardiogenic area forms a pair of elongated strands called cardiogenic cords. These cardiogenic cords enteric nervous tissue. 1. Foregut – contains the oral cavity, oesophagus, develop a hollow centre and are now called trachea and stomach endocardial tubes. Lateral folding of the embryo cause 2. Midgut – contains the small intestine and the the paired endocardial tubes to approach each other pancreas. It is herniated so it is visible on the exterior and form a single tube called the primitive heart tube. surface. Because the midgut is herniated it undergoes 3. The primitive heart tube develops 5 distinct areas – rotations o it can be packaged up and as development 1. Sinus venous – which develops into the right continues the ventral wall will close around the atrium and into the sinoatrial node. midgut. 2. Atrium – develops into right and left atrium 3. Hindgut – contains the colon. 3. Ventricle – develops into left ventricle 4. Bulbus cordis – develops into right ventricle 5. Truncus arteriosus – develops into the ascending aorta and pulmonary trunk The Structure Of The Placenta The placenta has a maternal placental side and a foetal placental side. The placenta acts as a barrier between foetal circulation and maternal circulation. It is very important to remember that the circulations systems are separate and that the placenta provides and interface for oxygen and nutrient diffusion. • The foetus floats in a sack called the AMNION. It is the theoretical space which contains the foetus and the amniotic fluid. • The amnion is filled with AMNIOTIC FLUID. • The CHORION is a membrane that surrounds the amnion. • Outside the chorion there is the YOLK SAC and the PLACENTA. • The UMBILICAL CORD protrudes from the foetus through the amnion and into the placenta. • The placenta is attached to the uterine wall The placenta has a maternal placental side and a foetal placental side. The placenta acts as a barrier between foetal circulation and maternal circulation. It is very important to remember that the circulations systems are separate and that the placenta provides and interface for oxygen and nutrient diffusion. The Foetal Side of the Placenta • Inside the foetal placental there are finger like projections called FOETAL CHORIONIC VILLI. They are foetal derived tissue. • The foetal chronic villi have two layers. The outer layer is the syncytiotrophoblast. The inner layer is the Cytotrophoblast. • The foetal chronic villus exists in the intervillous space. Chronic villus break down the maternal capillaries by proteolysis. This breakdown of maternal capillaries means that the intervillous space is filled with maternal blood inside the placenta. • Due to the syncytiotrophoblast being the outer layer of the chronic villi the cells are in direct contact with the intervillous space and therefore also in Contact with the maternal blood. • As the chorionic villi mature in later pregnancy, Cytotrophoblast reduces to produce single layer of Syncytiotrophoblast giving closer contact of maternal and foetal blood. The foetal blood supply = the umbilical cord. The foetal bloody supply consists of umbilical arteries and umbilical veins. 1. Umbilical arteries – carry deoxygenated and nutrient poor blood from the foetus to the placenta. 2. Umbilical veins – carry oxygen and nutrient rich blood from the placenta to the foetus Diffusion of the oxygen and the nutrients happens from the maternal blood into the umbilical veins in the intervillous space which is bathed in maternal blood. The chronic villus contain umbilical veins and arteries. Foetal Circulation In a healthy new-born baby the blood flows into the right atrium of the 1. When blood enters the foetal heart through the right atrium heart, then to the right ventricle and out through the pulmonary artery towards the lungs where the blood becomes oxygenated, the blood then most of the blood flows into the left atrium through the heads back to the heart and into the left atrium and into the left ventricle Foramen Ovale. This blood then flows out via the aorta and and through the aorta to the rest of the body to oxygenate the tissues. circulates to the body including the brain and the limbs where the blood becomes deoxygenates and flows into the placenta As we know the foetus relies on the blood from the mother to oxygenate it. through the Umbilical Artery where it becomes oxygenated and flows back towards the heart. We know that placenta provides a surface of gas exchange between the 2. Some of the blood that didn’t make it into the left atrium flows umbilical arteries and umbilical veins and therefore the foetus does not into the Pulmonary Artery and this is where the stunt known as need to direct blood towards the lungs. The placenta sort of becomes the the Ductus Arteriosus flows the remaining blood into the aorta lungs of the foetus as is the site of carbon dioxide and oxygen exchange. and the blood follows the same path to the body and then the Therefore the foetus has 3 SHUNTS TO DIRECT BLOOD. placenta via the umbilical arteries. 1. Foramen Ovale – this is a space that connects the left 3. When the oxygenated blood flows away from the placenta via the umbilical veins in the umbilical cord, it flows to the liver. atrium and right atrium. Its purpose is to bypass the 4. Blood reaches the inferior vena cava and then most of this lungs. blood is sent through the Ductus Venosus , this shunt directs 2. Ductus Arteriosus – which directs blood from the some of the highly oxygenated blood to bypass the liver and go straight to the vena cava and then into the right atrium of the pulmonary artery into the aorta. heart. 3. Ductus Venosus - this shunt directs some of the highly 5. A small amount of this blood goes straight to the liver to give it oxygenated blood to bypass the liver and go straight to the oxygen and nutrients it needs. the vena cava and then into the right atrium of the heart. The ductus venosus, the ductus arteriosus Very Very High yield content and the foramen ovale remain open until for Sem 1 Exams. They will ask you about this birth. Age And Pregnancy Ovarian Reserve At early embryo genesis of a fertilised egg the ovum begins to develop. Primordial germ cells which make up the reproductive parts of the embryo produce primary oocytes. At roughly 20 weeks gestation there is a peak number of oocytes formed at about 7 million. A female is born with all the primary oocytes/ potential eggs she will ever have in her life. As the pregnancy progresses cell death occurs where the number of primary oocytes/ primordial follicles formed is at around 2 million. These eggs enter the process of meiosis 1. At birth meiosis arrests and the baby is born with around 1 million primary oocytes. At late embryogenesis meiosis resumes in puberty under the influence of gonadotrophins FSH and LH in the monthly menstrual cycle. As women increase in age the number of primary oocytes that are in the ovary begin to decrease, this is because some oocytes are released into the fallopian tube for fertilisation in ovulation and roughly each month 20 primordial follicles are chosen to mature but are not chosen to become the dominant follicle and they are then destroyed and depleted in a process called follicular atresia. In a females life time only approximately 500 oocytes result in ovulation. The number of oocytes present in a females ovary decreases until there is very little to none left to mature and select for ovulation. This phase in a females life is called menopause. Ultrasounds Ultrasounds are used diagnose and help treat Early ultrasound done at 12-13 days babies and mothers (clinical monitoring of early • Can be done transvaginal or transabdominal pregnancy). An ultrasound produces high frequency • Can see the Gestation sac sound at 1-5MHz pulse. The frequency will bounce • Day 12-13 of development Very back at different tissue interfaces and Reflection is • Chorionic cavity of the developing pregnancy high • Circular bright ring (decidual reaction) dependent on tissue density. The reflections will yield then portray and image on the screen. Ultrasound at 12 weeks (booking ultrasound) • Active Infections –all women There are two types of ultrasound: • Urine infections, HIV, Hep B, Syphilis and Red cell antibodies –all women 1. Transvaginal (TV) - about the time of the missed • Pregnancy described as viable when foetal heart pulsations seen – 6 weeks period • Rapid placental growth and development – faster than the embryo 2. Transabdominal (TA) - from 5 weeks from Last • Organogenesis – 6-10 weeks menstrual period Ultrasound scan at 20 weeks (the anomaly scan) There are 3 types of ultrasound images: • The longest scan which can last between 60 and 75 minutes depending on 1. 2D image - takes thin slices in 2 planes the risk category of the baby and the mother. • Known as the anomaly scan, However, detection rates of some abnormalities 2. 3D image - takes thin slices in 3 planes – re- is poor. models images to give more realistic image • Foetus is fully formed , No further organogenesis, As foetus gets bigger, better 3. 4D image - as 3D, but adds movement and clearer to see • The embryo is roughly 15cm long • At the 20 week scan we can see the sex of the baby. • Down syndrome screening – we can detect 75% of down syndrome cases in the first 20 weeks. We do this by measuring hormones - beta HCG (high), Inhibin A (high), unconjugated Estriol (E3) (low), PAPP-A (low), Alpha fetoprotein (AFP) (low). • Exomphalos – in normal development of a foetus the Gut is exteriorised and rotates in 1st trimester before returning inside however in a condition called exomphalos the gut remains outside of the body. Collapsing Corpus Luteum Cyst A corpus luteum cyst is simply a cyst that forms inside the corpus luteum. This is caused by a build-up of fluid inside of the corpus luteum, it is a type of functional ovarian cysts. In most cases, corpus luteum cysts will go away on their own without treatment. Corpus luteum cysts may disappear in a few weeks or take up to three menstrual cycles to vanish altogether. Some women may experience a burst cyst, which can cause severe pain and possibly internal bleeding. Larger cysts can cause the ovary to twist on itself (ovarian torsion) which can negatively affect the blood flow to the affected ovary. At times, the corpus luteum cyst may remain past the early stages of pregnancy. If this happens, the cyst has the potential to cause problems. An obstetrician will monitor as appropriate and make referrals to specialists as necessary. Labour The Foetal Contributions/Role In Labour Induction Of Labour The foetus has something called a HPA axis. This HPA axis is supressed during pregnancy but matures prior LABOUR IN ANIMALS The triggers of labour are poorly understood. It is suggested that the maternal, foetal and to birth. It leads to a production of cortisol and DHEA placental actions all play a role in inducing labour. In studies conducted on animals just made by the adrenal gland. Cortisol upregulates COX- before labour occurs there is a significant decrease in the amount of progesterone being 2 enzyme which increases prostaglandin 2 alpha PGE2 produced. . DHEA becomes a substrate for placental oestrogen • The drop in progesterone will begin the remove the suppression of the myometrium and so it can begin to contract. production prior to labour. • The enzyme COX-2 is synthesised and upregulates which increases the amount of The ‘placental clock’ refers to the idea that it is the prostaglandin being produced. Prostaglandin induces myometrial contractions There placenta that stimulates labour. The placenta is an increase in oxytocin pulsality – causing myometrial contractions • There is a stimulation of white cells – leukocytes – which releases proteases and synthesises CRH and it increases towards the end of prostaglandin E2 which act on the cervix and induce myometrial contractions. pregnancy why may trigger foetal HPA action. • All of which accumulates to stimulate labour. Quick overview of labour HOWEVER – in humans there is no fall in progesterone. 1. Onset of human labour is poorly understood. 2. Proposed that the placenta functions as a clock for labour. MIFEPRISTONE - blocks to action of progesterone and therefore is used commonly in 3. It secretes CRH which activates the Foetal HPA axis. pregnancy terminations. At the end of the pregnancy although the amount of 4. There is a high surge in oestrogen and at the same time the progesterone in the body remains the same, the myometrial is less responsive to myometrium becomes less responsive to progesterone. progesterone and this is because it is medicated by the changes in progesterone 5. Prostaglandins and oxytocin are produced. 6. The causes the cervical ripening. receptors of the myometrial. 7. Inducing myometrial contractions which lead to labour. Another trigger of labour is possibly oestrogen. The levels of oestrogen increase in the lead up to the end of the pregnancy. There is an increase of oestrogen receptors in the Understanding the roles of the hormones and myometrium. As progesterone is used less and the oestrogen levels rise, oestrogen becomes the dominant hormone. This leads to the activation of the myometrium. This drugs in labour Is high yield – THEY WILL ALWAYS happens by stimulating gap junctions, increasing the oxytocin receptor expression in the ASK YOU HOW MIFEPRISTONE WORKS AS A myometrium and increased production of prostaglandin and oxytocin. TERMINATION PILL – YOU NEED TO KNOW THIS The Birthing Process Labour is defined as regular uterine contractions causing cervical Oxytocin and its role in labour and delivery: • Oxytocin is a peptide hormone. It is released from the dilation. Normal labour occurs at weeks 37 and 42. There are 3 stages posterior pituitary gland in a pulsatile manner. The pulsatile of labour: motion and the release of oxytocin is controlled by the • Stage 1 = cervical dilation 0-10cm. this is split into two phases called the latent phase and the active phase. The latent phase is from 0-4 nearby hypothalamus. cm and the active phase is after 4 cm and this usually follows a strict • At labour the pulsality increases of the posterior pituitary gland there’s the amount of oxytocin being secreted windowed process. increases. This level of oxytocin is furth increased as the • Stage 2 = decent and delivery of the foetus at 10 cm. this is caused uterus produces its own small amount of oxytocin. by a combination of uterine contractions and maternal pushing • Stage 3 = delivery of placenta and membranes – a large uterine • Myometrial cells in the uterus have receptors for oxytocin, so when oxytocin binds to these receptors, it stimulates contraction contracts down on the uterine bed to prevent uterine myometrial contractions. haemorrhaging. • A synthesised form of oxytocin called SYNOCYTOCIN is produced and obstetricians can use this drug to argument How The Cervix Changes In Labour • The cervix is made of around 80% connective tissue. labour and treat bleeding. It treats bleeding by stimulation a long contraction and this pushes down on to the uterine bed • The cervix remains closed during the pregnancy up until the to prevent further haemorrhaging after childbirth. onset of labour. • The cervix under go’s a process where It ripens, softens, effaces Uterine Contractions (shortens) and then dilates. This occurs under the influence of During pregnancy oestrogen stimulates uterine smooth muscle to undergo hypertrophy and hypoplasia to accommodate growing foetus. In mechanical stimulation from pressure of the baby’s head and the run up to labour the uterus becomes sensitised to a hormone called the influences of inflammatory mediators. oxytocin which is a hormone that causes contractions. The uterus also • Inflammatory mediators – leukocyte infiltration into the cervix starts to become de sensitised to the effects of progesterone. During the which release proteases and prostaglandin E2 which act on the cervix. entire pregnancy progesterone is used to suppress myometrial contractions in pregnancy and prevents preterm labour. Baby Adaptations At Birth 1. This involves the three structures – the foramen ovale, the ductus arteriosus, the ductus venosus. (detail in the foetal circulation section Very high Yield above) you will be asked 2. All of these structures remain closed up until birth. about these 3. At birth the umbilical cord which is attached to the placenta is clamped structures in off which means the baby is no longer receiving oxygen and nutrients Sem1 and Sem 2 from the mother and therefore the lungs need to start working in order for the foetus to be able to survive and the heart must anatomically change so that blood flow is no longer directed to the umbilical cord but is directed to the lungs instead. 4. A few minutes after birth the ductus arteriosus and the ductus venosus will fully close 5. An increase in the pressure on the left side of the heart and a decrease in the pressure of the right side of the heart causes the foramen ovale to close like a valve and complete shut creating two separate chambers (the left atrium and the right atrium). 6. The redirection of the blood means that the body begins to be oxygenated by the breathing of the foetus. 7. The blue tint to the baby when it is born is because the body is poorly deoxygenated, the baby will begin to pink up when the 3 shunts close and the blood is being pumped around the body correctly and the cells are receiving oxygen. YouTube Videos To Watch Ovulation And Fertilisation • https://www.youtube.com/watch?v=EwTZ1fypivg – ovulation, Oocytes/Female Gametes Fertilization, Zygote, Blastocyst. • https://www.youtube.com/watch?v=Msrym4oGVSk – gives a good • https://www.youtube.com/watch?v=UAScTbIt1Dc – fertilisation and understanding of what an oocyte is and what happens to it during implantation. menstruation. • https://www.youtube.com/watch?v=E50qKoSSaS4 - Gastrulation and • https://www.youtube.com/watch?v=u0FogWIJkHA – great at Neurulation – great diagrams in this video. understanding the very basic structure of an oocyte. https://www.youtube.com/watch?v=w9tJ7UiLrQs – video specifically on • https://www.youtube.com/watch?v=1cskfSs7mAs – a great video gastrulation explaining the different stages of an oocyte. Lots of questions are asked on • https://schoolbag.info/biology/mcat/13.html - very complex website the structures of the different oocytes and the differences. detailing stages of foetal development, way too advanced but may answer some questions if you want to learn in more detail. Menstrual Cycle • https://www.youtube.com/watch?v=2_owp8kNMus – great video for Extraembryonic Membranes menstruation. The main video I used. • https://www.youtube.com/watch?v=czjfWCaa4Fw – covers the 4 main https://www.youtube.com/watch?v=7HlHGLr1hTA – good video by extraembryonic membranes that are formed. osmosis for menstruation if the first video was confusing. • https://www.studocu.com/en-gb/document/university-of- • https://www.youtube.com/watch?v=8ZT-eqdNsGA – again about the sheffield/embryology/lecture-notes-on-embryology-and-biological- menstrual cycle by good diagrams to explain the uterine cycle and the development/1206562 - university of Sheffield notes on all the topics of effect on the endometrial lining. foetal development. • https://teachmephysiology.com/reproductive -system/development- • https://www.youtube.com/watch?v=F2LeGbEbcrw – 3 germ layers maturation/menstrual-cycle/ - good to read to understand the different mnemonic. Common questions on what do the 3 germ layers form. hormones used in menstruation. Questions are asked on the roles of the different hormones and the differences. Important to understand when Neuralisation understanding the role of contraceptives. • https://www.youtube.com/watch?v=vvBBFOu9h1w – great video detailing • https://www.youtube.com/watch?v=VYSFNwTUkG0 – another good video the whole process. Important to understand the basics of this process as it on the ovarian cycle and also good for the structure of the oocytes. is learnt in more depth in semester 3. • https://www.youtube.com/watch?v=E50qKoSSaS4 – same video as above, but great images detailing the process. Physiological changes during pregnancy - https://www.youtube.com/watch?v=dLsy2pJjTEg Cardiac Development • https://www.youtube.com/watch?v=-d2UfOePgZw – slightly more detail Pregnancy Test - https://www.youtube.com/watch?v=I6jE99Fjbvo – recap than required for the exam, but great visuals to understand the process and of how a pregnancy test works. Exactly the same content as A-Level, I used the folding. my old AQA A-level book. • https://www.youtube.com/watch?v=a0qyagIgBPw – short visualisation the process. NIPT - https://www.youtube.com/watch?v=TnlnLXX2HEE Placenta Folic Acid - https://www.youtube.com/watch?v=Zi_oBb_FxX4 • https://www.youtube.com/watch?v=gbextFwqnY4 – perfect video for understanding the 5 key roles of the placenta which matches the lectures. Contraceptive pill - https://www.youtube.com/watch?v=hI2C7TsnSfk https://www.youtube.com/watch?v=Dt2scIqwIls – important video in important to understand how the oestrogen and progesterone work to understanding the development of the placenta. prevent pregnancy, there has been questions on how the contraceptives • https://teachmephysiology.com/reproductive-system/fetal- work. physiology/placental-development/ - good read to understand the difference cells in the placenta. Labour https://www.youtube.com/watch?v=w0iDfcAYZWc – stages of labour Foetal Circulation – very important to understand this topic, its tested on a lot https://www.youtube.com/watch?v=h7nOZ2kNfW4 – stages of labour and also is tested on in semester 2. Try to understand it well now so it’s easier inhttps://www.youtube.com/watch?v=wEyHd_Dc8t8 – cervical semester 2. contractions. • https://www.youtube.com/watch?v=zTXmaVgobNw – good video to explain https://www.youtube.com/watch?v=lsSbSKlThgQ – fantastic video to how the foetal circulation works. watch on pregnancy and labour, including oxytocin which is a common • https://www.youtube.com/watch?v=-IRkisEtzs k – another great video to question as well as theories of labour induction. Compliments the lectures understand the roles of the 3 shunts. really well. Surfactant - https://www.youtube.com/watch?v=UU9ij_z6jXQ – the Have a look through the different topics in this link as it may be useful to theory of surfactant. In case 1 there is more of an emphasis of what consolidate ideas - https://teachmeanatomy.info/the-basics/embryology/ happens to babies born prematurely without surfactant. But surfactant is very important in semester 2 when you do respiratory, so it a great concept to understand now. CASE 1 Anatomy • https://www.youtube.com/watch?v=tdlmHi0n0Ss – understanding the bony pelvis. Common questions in exams and also in CCA exams. • https://www.youtube.com/watch?v=yzjnbOP_x4E – sacrum anatomy. • https://www.youtube.com/watch?v=J3oky60tXCc and https://www.earthslab.com/anatomy/ovaries/ – need to understand the anatomy and positioning of the uterus. The ligaments of the uterus are common questions as well as their roles in supporting the uterus and ovaries. • https://www.youtube.com/watch?v=AREHaMls9Y4 – this is great video using the models. This model is very similar to the ones in the DR and are common questions in the CCAs in semester 2, so try to be familiar with the models. You wont be tested on models like this in semester 1 but you will in semester 2. • https://teachmeanatomy.info/pelvis/female-reproductive-tract/ovaries/ - the ovaries, their histology, position, ligaments and neurovascular supply. • https://teachmeanatomy.info/pelvis/female-reproductive-tract/uterus/ - the uterus, structure, position, histology, ligaments, vasculature and lymphatics. • Fallopian tubes - https://teachmeanatomy.info/pelvis/female-reproductive-tract/fallopian-tubes/ • In general check out this section of teach me anatomy as it will be very helpful to understand the female reproductive organs - https://teachmeanatomy.info/pelvis/female-reproductive-tract/ • Pelvic girdle - https://teachmeanatomy.info/pelvis/bones/pelvic-girdle/ - would highly recommend reading this, a lot of CCA questions are about identifying inlet and outlet borders etc. good diagrams. The boundaries might be different on the anatomy virtual resources, so use them if different. • Sacrum - https://teachmeanatomy.info/pelvis/bones/sacrum/ CASE 1 Histology Histology is very hard. The best way to learn histology is to look at as many different slides as you can, online, YouTube or in books and practice labelling different structures, layers and cells. Niggy’s lectures are great and the slides she uses are common ones in the CCA exams in Semester 2. But these videos below are really helpful in revision. • https://www.youtube.com/watch?v=XiOPMzq34N0 – Ovarian Histology • https://www.youtube.com/watch?v=IezWjLUMd8M – Uterine Histology • https://www.youtube.com/watch?v=yNVG-3q2MwU – Fallopian Tube Histology • https://www.youtube.com/watch?v=G_r-PrfDM00 – Vaginal Histology In my revision for histology I printed different slides off, laminated them and practiced labelling them with a whiteboard pen. In the exam they ask you identify cells and layers and are very specific. They can also ask you stage e.g. stages of cells change or layers like the follicles, the uterine walls and about whether cells are contracted (Sem 2).