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IV. Splanchnology, Histology and Embryology Topic 1-51 2008 1. The anatomy, histology and cyclic changes of the ovary. The oogenesis: primary, secondary and Graafian follicles. Anatomy Almond shaped organs on the posterior aspect of the broad ligament (not enclosed by it), on the side wall of minor pelvis and the external and internal iliac vessels enclose it. It is covered by mesovarium which posteriorly attaches it to the broad ligament. The suspensory ligament of the ovaries attaches the ovaries to the lateral pelvic wall. The ligament of ovary (remnant of ovarian gubernaculums) attaches it to the uterus. Blood supply: Ovarian arteries ← abdominal aorta, which anastomoses with the branches of the uterine arteries (found in the suspensory ligament). Drainage: pampiniform plexus → ovarian veins, Right → IVC and left →left renal vein. Lymphatic drainage: drain into the lymphatics of the uterus and then to the right and left lumbar lymph nodes. Innervation: Both the uterine and ovarian plexuses. Sympathetics → T11-L1 spinal sensory ganglia, Parasympathetic → inferior hypogastric plexus → S2-S4 spinal sensory ganglia. Histology Surface covered by simple squamous or cuboidal ept. → germinal ept. Tunica albuginea (dense CT) is found underneath this and provides the whitish colour. And then the cortical region containing the oocytes primarily, but also the stroma (CT) which is spindle-shaped fibroblasts. Medullary region contains the vascular bed. It is developed from the yolk sac; primordial cells migrate to the gonadal primordial (after about a month) → oogonia. In the 3rd month they enter meiotic division but stop at the diplotene stage (primary oocytes with follicular cells). The cyclic changes Ovulation: 14th day of the menstrual cycle. Ovulation involves rupture of the follicular wall and liberation of the oocyte. It is stimulated by LH hormones released from the anterior pituitary gland in response to high amounts of circulating estrogen. Blood increase to the site as well as local release of histamine, prostaglandins, vasopressin and collagenase. Granular cells become loose and follicular cells weak. Just before ovulation blood cease in the area and it changes in colour. First meiotic division is finalised and the oocytes enters the oviducts. If not fertilised within 24 h it degenerates. Theca interna, theca externa and the granulosa cells become the endocrine gland called the corpus luteum after ovulation. The follicular wall becomes folded when oocytes is released and blood flow into the cavity (corpus hemorrhagium). It coagulates and is invaded by CT. The granulosa lutein cells makes up 80% of the corpus luteum. It starts to secrete estrogens and progesterone and continues for 10-12 days. When the progesterone ceases to be secreted the uterus begins menstruation if no fertilisation has occurred. After both stops the body once again start to secrete follicular stimulating hormones. New menstrual cycle begins. The remnant of corpus luteum is phagocytosed and becomes a scar tissue called the corpus albicans. And the cycle begins all over again with the stimulation and growth of 15-20 primary oocytes. But only one will reach maturity. If pregnancy occurs the human chorionic gonadotropin hormone will rescue the corpus luteum from degeneration and aid in the implantation of the embryo. The oogenesis Primordial follicle (formed during fetal life) → primary oocytes and a single layer flattened cells (most spf of the cortical region). Large nucleus and large nucleolus. First prophase of meiosis. Puberty → The primordial follicle enlarge and multiply its organelles. Follicular cells proliferate and form granulosa cells. As well as the zona pellucida (glycoprotein) are formed around the oocytes. Move deeper, antrum begins to form through the accumulation of fluid. And are now called secondary follicles. Some cells form the cumulus oophorus which is the cells holding the oocytes and the ones immediately next to the oocytes are the corona radiata. Theca interna (produce steroids; androstenedione, estrogen) and theca externa is formed. Estrogens inhibit the release of FSH. Blood vessels penetrate in to the interna. The graafian follicle is produced (one) per menstrual cycle. Granulosa layer becomes thinner, but the theca layers thicker. It also increases in size. ≈ 90 days 2. The anatomy, histology and cycle of the uterus – histological and hormonal changes. Anatomy It is a pear-shaped hollow organ, which is anteverted (90o at junction of cervix and vagina) and anteflexed (160o at junction of cervix and body). It is held and supported by the pelvic and urogenital diaphragm as well as the round, broad, lateral, transverse, pubocervical, sacrocervical and rectouterine ligaments. Broad ligament covers it. Uterine tubes are covered by the mesosalpinx. Anterior surface rests on the bladder. Divided into 4 parts: Fundus (superior and anterior to the plane of entrance), body (continuous with the internal os), isthmus (constricted part) and cervix (projects into vagina and has the internal os, cervical canal and the external os). Blood supply: Uterine artery primarily but also the ovarian artery. Drainage: the uterine veins form the uterine venous plexus → internal iliac veins. Lymphatic drainage: Mainly into the lumbar lymph nodes but also into the external iliac, internal iliac and sacral lymph nodes. Innervation: Uterovaginal nerve plexus → inferior hypogastric nerves. Histology The wall of the uterus consists of 3 layers. Outer layer is the serosa (CT and mesothelium) or adventitia (CT). Middle layer is the myometrium and is the thickest layer. It is composed by smooth muscle bundles and CT in 4 layers, 1st and 4th is longitudinal. Middle layer holds the blood vessels. Hyperplasia and hypertrophy in pregnancy. Inner layer is the endometrium, consisting of ept. and lamina propria with simple tubular glands. Ept. → ciliated or secretory columnar cells. Lamina propria is rich in fibroblasts, ground substance and collagen II. This layer can be divided into basal and functional layer. Supplied by straight respectively spiral arteries. Menstrual cycle After menstruation for about 10 days the uterus goes through the proliferative phase, during which the ovarian follicles grow rapidly and secrete estrogens. The estrogens act on the endometrium and it begins to reconstruct. Endometrium becomes covered with simple columnar ept. And the glands are becoming straight tubules. This layer becomes 2-3 cm in the end of the proliferative phase. In the secretory phase which starts after ovulation, as a result of progesterone, glycogen accumulates in the ept. cells of the glands and the lumen of the glands close. The glands become highly coiled and CT oedematous, it reaches its maximum thickness. Menstrual phase follow as an effect of decrease in levels of progesterone and estrogens. The relaxation and contraction of the spiral arteries, activation of locally produced matrix metalloprotinases, and secretion of prostaglandins, cytokines and nitric oxide cause the breakdown of the vessels, collagen and basement membrane. Blood vessels rupture above constrictions and begin to bleed, due to necrosis. Functional layer of the endometrium is detached. This phase lasts for 4-5 days. 3. The anatomy and histology of the testis and the epididymis. Spermatogenesis; the electron microscopic structure of the spermatozoon. Anatomy Testis - Develops and descends retroperitoneal. Descended into the scrotum by the spermatic cord. Can be found in under the visceral layer of the tunica vaginalis and is covered by the tunica albuginea. Tunica albuginea thickens posteriorly into the mediastinum of the testis. From this septa extends inwards, dividing the testis into lobules. In between we find the seminiferous tubules which join the rete testis by the straight tubules. Tunica vaginalis is a closed sac of peritoneum. A slit-like recess divides the testis from the epididymis. It produces spermatozoa and secretes sex hormones, primarily testosterone. Blood supply: testicular artery ← abdominal aorta. Anastomose with the artery of the ductus deferens. Drainage: Pampiniform venous plexus. Lymph drainage: Testicular vessels into lumbar or superficial scrotal nodes. Epididymis - Head, body and tail. Convoluted duct that is 6m long. Receive spermatozoa through the efferent duct from the testis. The epididymal ducts are so tightly pact that they seem solid. Becomes progressively smaller. It is responsible for maturation, storage and propulsion of spermatozoa. Ductus deferens - Begins in tube of epididymis. It is a thick tube enters pelvis at deep inguinal ring lateral to the inferior hypogastric a. Crosses umbilical a. and obturator n. and v., dilates into an ampulla in the end part. Join the seminal duct to form the ejaculatory duct. It is the primary component of the spermatic cord and contains fructose. Blood supply: Artery of the ductus deferens ← superior vesical artery. Drainage: Testicular vein and pampiniform plexus. Lymph drainage: External iliac lymph node Innervation: Hypogastric and pelvic plexus. Histology Testis - In the testicular lobules divided by the tunica vaginalis which is a serous sac, we find loose CT, 1-4 seminiferous tubules and Leydig cells. Leydig cells secrete testicular androgens, and the seminiferous tubules produce spermatozoa. Tunica vaginalis consists of a visceral and a parietal layer with a fluid in between on the anterior and lateral sides of testis. This fluid allows movements of the testis in the scrotum. The seminiferous tubules produce up to 2x105 spermatozoids per day. We have 100-250 tubules. Have seminiferous/ germinal ept. basal lamina and fibrous CT. In the fibrous CT we find myoid cells which adhere to the basal lamina and have the same characteristics as smooth muscle. The epithelium has Sertoli’s cells, supporting cells and spermatogenic lineage. Sertoli’s cells nurture the maturing spermatozoids and secrete anit-Müllerian hormone, inhibins and activins, androgen binding protein and GDNF. Forms the blood-testis barrier. Mediates exchange, protect against immunological attack. Epididymis - One of a few regions in the body that has stereocilia on its pseudostratified columnar ept. Which also has principal (tall columnar) and small basal (spherical) cells. Long convolutes tubule which is surrounded by CT and a thin smooth muscle layer. Smooth muscle contract to expel the sperm cells during ejaculation. This layer is divided into 3 layers, and inner longitudinal, middle circular and an outer longitudinal. Adventitia surrounds the smooth muscle, and merges with the CT of the spermatic cord, also holds the nerves and vessels. Spermatogenesis This is the production of spermatozoids. The line starts with a spermatogonium (12 μm) next to the basal lamina and is divided by mitosis into a type A spermatogonia (stem cell) and type B spermatogonia (progenitor cell). The type B spermatogonia then divide into a primary spermatocyte and it still has 46 chromosomes. Then it enters prophase of meiosis and this last 22 days and majority of them are in this phase. Then it divides into a secondary spermatocyte after the first meiotic division, this is smaller and shortlived, because it quickly divides further into a spermatid which now has diploid number of chromosomes, 23. It is 7-8 μm and the chromatin is condensed, it has also moved close to the lumen of the seminiferous tubule. It enters the spermiogenisis, in which there is no cell division. It starts with the golgi phase in which PAS positive granules accumulate in the golgi complex and form an acrosomal granule within the acrosomal vesicle. The centrioles migrate to opposite poles, the flagellar axoneme forms from the centriole and the centrioles move back to the nucleus. Spin out axonemal components. Acrosomal phase is when the acrosomal vesicle covers anterior nucleus, form the acrosome which serves as a lysosome. Nucleus orients towards the base of the seminiferous tubule. Centriole form the flagellum and mitochondria aggregates around the flagellum. Maturation phase is when the cytoplasm shed and the spermatozoa are released into lumen of the tubule. Spermatozoon 4. The ovulation, fertilization, cleavage and implantation. The formation and structure of the placenta. Structure of the mature placenta. Ovulation Just before the oocyte is expelled it goes through the final stages of meiosis I and the secondary follicle grows rapidly. Up until 3 h before ovulation the oocyte is going through meiosis II, but ceases in metaphase. The stigma appears (bulging of the ovary). LH surge, causing prostaglandins to increase and this in turn makes the musculature of the ovarian wall to contract. Collagenase activity is also increased and collagen in the follicular wall is digested at a higher speed. The contractions together with the weakening of the follicular wall cause ovulation; this is when the oocyte is expelled with the cumulus oophorus. These granulosa cells will then form around the zona pellucida forming the corona radiata. Sweeping movements of the fallopian tubes and its fimbriae picks the oocyte up and contractions move it to the uterus, which usually take 3-4 days. Fertilization Fertilization usually occurs in the ampullary region of the uterine tubes. The sperm can remain alive in the uterus for days. Only 1% of the sperm makes it through their ciliary processes to the uterus. Once reaching the isthmus they become less motile until ovulation when chemicals released from the cumulus oophorus attracts them. Then they undergo capacitation; which is a process that takes about 7 h and includes the removal of plasma proteins and glycoprotein coat on the acrosomal region of the spermatozoon. Then it can feely move throught the corona radiata, only one though. The others are thought to aid in this. The acrosome reaction that follows are the binding to the zona pellucida (mediated by ZP3) and the expulsion of the enzymes needed to penetrate it. Once penetrated the zona pellucida changes its chemical composition to make sure that only once spermatozoon will fertilize the egg. As soon as the wall has been broken meiosis II is finished. The spermatozoon swell and form the male pronucleus, tail degenerated and when the female and male pronucleus comes in contact with each other they loose their nuclear envelopes. The cells fuse and diploid number of chromosomes are restored, determination of sex can be done and this initiates cleavage. Cleavage It cleaves and forms two cells, which is the start. With each cleavage after this (mitosis) the cells become smaller. They are called blastomeres. Compaction follows after the third cleavage, which is the binding of the blastomeres into a little compact ball with tight junctions between them. When the 3rd day is reached the blastomeres divide again and form a morula (16 cells), this is the first time there is segregation between inner and outer cells. Inner gives rise to the embryo and the outer the trophoblast which becomes the placenta. Implantation The mucosa of the uterus is in secretory phase and 3 layers can be distinguished, compact, spongy and basal. The blastocyst usually implants itself between glands on the anterior or posterior wall of the uterus. Implantation can first occur after the zona pellucida has appeared. Implantation occurs in about the 6th day and it is the trophoblasts that penetrate between the epithelial cells. L-sectin binds to carbohydrate receptors of the uterus. Placenta The placenta develops during the 2nd month. The radical appearance of the trophoblasts (villi) will produce a stem villi which extends from the mesodermal chorionic plate to the cytothrophoblast shell. These cells also form the vascular portion of the structure, over which a syncytium layer is found. This capillary system that is forming come in contact with the chorionic plate and gives rise to an extra embryonic vascular system. Maternal blood is delivered through the spiral arteries of the uterus. The connection is formed by the cytotrophoblasts, they form a hybrid vessel between maternal and fetal blood circulation. Increasing the flow of maternal blood into the intervillous space and making the spiral arteries larger. Villi begins to extend out during the next few months and the syncytium becomes very thin. Now called the chorion frondosum together with the decidua basalis is becomes the placenta. It has two portions the fetal portion and the maternal portion. This is bordered by the decidual and the chorionic plate. The border which is a mix of the two types of cells is very rich in amorphous extracellular material. Between these two borders the blood filled intervillous space can be found. It is filled with maternal blood but lined by fetal syncytium. In 3 rd to 4th month decidual septa (still covered by fetal syncytium) extends into the intervillous space and divides it into cotyledons (compartments), but contact between them is not abandoned. It will also expand in surface up to 15-30% of the internal surface of the uterus. Full-term placenta is 15-25 cm diameter and 3 cm thick. Then one can clearly see about 15-20 cotyledons divided by decidual septa, this from the maternal side. The fetal surface is covered by the chorionic plate, which in turn is covered by the amnion. 5. The structure of the blastocyst and the formation of the embryonic disc. The formation of the amnion and the yolk sac; neurulation. Derivatives of the germ layers. Blastocyst When the morula enters the uterine cavity fluid penetrated through the zona pellucida and after a while a cavity is formed, the blastocele. This structure is what is called a blastocyst. Inner cells are called embryoblasts and outer cells are called trophoblasts. The zona pellucida finally disappears. This structure is then implanted in the uterus around the eight day. After this the trophoblast layer is divided into 2 layers the inner cytotrophoblast layer and the outer syncytiotrophoblast layer. It is the inner layer that is mitoticly active, and provide the outer cell layer with new cells which loose their membranes. The embryoblast layer will also divide into 2 layers, inner hypoblast layer (cuboidal cells close to the blastocyst cavity and an outer epiblast layer (high columnar cells adjacent to the amniotic cavity). The amniotic cavity develops within the epiblast layer at the same time as the bilaminar disc is formed. Epiblasts adjacent to the trophoblasts are called the amnioblasts. Endometrial site is highly vascularized and have glands secreting glycogen and mucous. Yolk sac and the amnion During day nine the trophoblasts begin to develop vacuoles that fuse to lacunae at the embryonic pole. The primitive yolk sac is on the other pole lined by flattened cells (forming a membrane) originating from the hypoblasts. By the 11th or 12th day the embryo is embedded into the endometrium. The lacunae from communication structures, the synctiotrophoblasts dig deeper into the endometrial wall exposing the sinusoids and they together with the lacunae form a continuous structure that is filled with maternal blood. The layer closest to the primitive yolk sac and the outer layer of the cytotrophoblasts forms 2 new layers, the extraembryonic mesoderm (cells of the yolk sac and within it a space will be formed called the chorionic cavity. Which will surround the primitive yolk sac except at the connecting stalk. Extraembryonic somatopleuric mesoderm lines the amniotic cavity and extraembryonic splanchnopleuric mesoderm lines the yolk sac. The decidua reaction includes the formation of polyhedral endometrial cells filled with glycogen and lipids. By day 13, the trophoblasts gain a villous structure and penetrate the synctiotrophoblasts. These columns are called primary villi. A new cavity is formed within the excoelomic cavity by the production of more excoelomic cells. Known as the secondary yolk sac, it is smaller than the primary one due to the pinching of excoelomic cysts. The extracoelomic cavity expands and forms the chorionic cavity, forming the chorionic plate inside the cytotrophoblast. At one place the extraembryonic mesoderm will traverse the chorionic cavity and this is called the connecting stalk. The stalk will develop into the umbilical cord. Embryonic disc Three germ layers will be formed during the third week, the ectoderm, mesoderm and endoderm. A streak will appear in the epiderm; this will divide it into a primitive node at the cephalic end surrounding the primitive pit. The invagination occurs, epiblast cells move to the pit, become flask shaped and slip beneath it. Controlled by FGF8. Some will then replace the hypoblasts becoming endoderm and some will lie between the epiblasts and the endoderm becoming the mesoderm and the remaining will form the ectoderm. After a while cells will spread laterally and cranially, until they finally establish contact with the yolk sac and the amnion. It begins flat and almost round, gradually becomes elongated and narrow at the caudal end. Caused by cells moving in the cephalic direction. The invagination will continue until the 4th week but after that start to regress. At the caudal part the invagination until 4th week is important because they at this point the differentiation of the germ layers continue until the 4th week. Derivatives Ectoderm- the ectoderm thickens at the 3rd week and forms the neural plate, which makes up the neural ectoderm. The substances causing this to form is the FGF, which together with BMP4 and TGFβ inhibits the action of the mesoderm and endoderm. FGF promotes the neural pathway and represses the BMP and upregulates chordin and noggin expressions, which inhibit BMP. The inducers of neurulation cause the ectoderm to become midbrain and forebrain tissue. Induction has occurred and the neural plate form neural folds and a neural groove. The folds approach each other until the neural tube has been formed. At day 25 the closure of the cranial neuropore occurs and the causal end becomes narrow, finishing the neurulation. The lateral border will form the neural crest and undergo an epithelial to mesenchymal transition replacing the mesoderm. These cells will migrate to form melanocytes in the skin, sensory ganglia, sympathetic and enteric neurons, Schwann cells and cells of the adrenal medulla. As well as craniofacial skeleton, cranial ganglia, glial cells and at the time of the closure form the otic placodes (maintenance of equilibrium) and the lens placodes (lenses of the eyes). Mesoderm- At the midline it proliferates and form the paraxial mesoderm and at the lateral sides it forms the lateral plate. Lateral plate will form 2 layers, the somatic mesoderm layer and a layer covering the yolk sac, the splanchnic mesoderm layer. These layers line the intraembryonic cavity. Paraxial mesoderm will organise into segments (somitomeres) and they form concentrically around a centre. These contribute to the mesenchyme in the head, but they will also migrate down to form 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 8-12 coccygeal pairs. Some of the coccygeal will disappear and the rest of the somites will form the axial skeleton. This is dependent on cyclic genes such as Notch and WNT. Lateral parts of the somites will in fourth week become loose and form cells called sclerotomes and form a loosely woven tissue called mesenchyme. Some of cells of the somites will move and become the cells of limbs and wall musculature. Dorsal sides of the somites will move to the ventral side and form myotome. Together with the dorsal segments the myotome will form the dermatomes. The intermediate mesoderm will form the urogenital structures. Caudally if will form the nephogenic cord, unsegmented mass, upper part it will form segmental structure. Lateral plate mesoderm splits into a parietal and a visceral layer. Mesoderm from the parietal layer will together with the ectoderm form the lateral and ventral body wall. Visceral layer will together with the endoderm form the wall of the gut. The parietal layer will also form the lining membranes in the body, such as the peritoneal, pleural and pericardial membranes. Blood islands first appear in the mesoderm, from differentiation of mesoderm into a cell called the hemangioblasts. Which in turn will form haematopoietic stem cells and angioblasts. After this vessels will be formed through angiogenesis. Quite soon after this there will be a specification between veins. Arteries and lymph vessels. First to be developed are the dorsal aorta and cardinal veins. Endoderm – Main organ to come form endoderm is the gastrointestinal system. It begins with a bulging into the amniotic cavity and a fold cephalocaudally of the embryonic disc. A head fold and a tail fold are formed. Anterior part will form the foregut and the posterior will form the hind gut, and of course the middle part will form the midgut (communicates with the yolk sac by the vitelline duct). The cephalic end will be lined by ecto-endoderm temporarily and this is called the buccopharyngeal membrane, this will later rupture to form a communication between the amniotic cavity and the primitive gut. This type of membrane will also be seen temporarily on the hindgut, the cloacal membrane. The embryo will bend and come into a rounded shape. This will be bound to the original endoderm by the vitelline duct until it is obliterated much later, at the same site the allantois is formed and this is important for the nutrition of the embryo. Endoderm gives rise to ept. lining of the respiratory tract, the parenchyma of the thyroid, parathyroid, liver and pancreas. Stroma of tonsils and thymus, the ept. lining of the urinary bladder and the urethra and finally the ept. lining of the tympanic cavity and the auditory tube. 6. The lateral and cephalocaudal foldings of the embryo: formation of the umbilical cord. The clinical importance of the fetal membranes and the amniotic fluid. Twinning and teratogenesis. Lateral and cephalocaudal foldings Is a response to the fast growth of the somites, making it first folded laterally. Ventral body wall is formed except for where the connecting stalk is still attached. This will become narrower after the foldings and form the vitelline duct. This is also important for the incorporation of the allantois duct into the embryo; this is what will remain connected to the connecting stalk. By the fifth week the allantois and umbilical vessels will be restricted to the region of the umbilical ring. Limbs will appear like small paddles in the 5th week, before this the head will grow, face, ears, nose and eyes. Formation of the umbilical cord At the fifth week the allantois pass through the umbilical ring together with the umbilical vessels within the connecting stalk, and the yolk stalk (vitelline duct) accompanied with vessels of the yolk stalk. There is also a third duct, the canal connecting the intraembryonic and extraembryonic cavities. The amniotic cavity will expand on the expense of the chorionic cavity. The amnion will also envelope the stalks crowding them together, forming the primitive umbilical cord. The allantois will obliterate, as well as the chorionic cavity after the expansion of the amniotic cavity. Followed by this the yolk sac will shrink and gradually obliterate. Intestines forming to quickly will temporarily form a physiological umbilical hernia. When allantois, vitelline duct and all vessels are obliterated all that will be left in the umbilical cord is the umbilical vessels and the surrounding jelly of Wharton. Clinical importance Amniotic fluid – clear watery fluid that is produced by the amniotic cells but is mainly derived from the maternal blood. Increases from 30 ml to 1000 ml at the end of the pregnancy. It serves as a protective cushion for the embryo. Absorbs jolts, prevent adherence of embryo to the amnion and allows for fetal movements. This is replaced every 3 hours. During child birth the amniochorionic membrane forms a hydrostatic wedge that helps to dilate the cervical canal. From fifth month the foetus drinks some of the amniotic fluid. Hydramnios (more) or oligohydramnios (less) are causes of different birth defects. Hydramnios occur when the mother is diabetic, congenital malformations and idiopathic causes. Club foot or lung hyperplasia cause oligohydramnios. Placental membrane – separates the maternal from the fetal blood by 4 layers, endothelial lining of the fetal blood vessels, the CT in the villous core, cytotrophoblastic layer and the syncytium. It is not a full barrier, some substances may pass while others do not, and substances that may pass is nutrients, gases and maternal antibodies. Most hormones may not pass, but some do at a very slow pace, such as thyroxin. It is a protective barrier, but some drugs and viruses can pass it, such as rubella, cytomegalovirus, coxsackie, measles etc. And they can cause anything from a simple infection to death of the foetus. Twinning and teratogenesis Dizygotic twins – result of simultaneous release of two oocytes and fertilization of both. These have no more likeness to each other than a normal brother and sister, and they may or may not be of different sex. Usually they develop within their own amnion, with their own placenta and chorionic sac. Although it can occur that the two placentas fuse together. Causing the blood cells of the twins to be dizygotic. Monozygotic twins – splitting of one oocyte at one stage, causing two twins to develop. Earliest this can occur is at the two cell stage. Two groups of cells within one blastocyst, they have a common placenta and chorionic cavity but their own amniotic cavity. Although the same placenta, the blood supply is even. They will have a very strong resemblance to each other. Triplets, quadruples, quintuples and so on are rare but can occur. Recently more of these births occur, mainly due to the use of gonadotropins of the mother. 7. The development and derivatives of the branchial apparatus. Pharyngeal arches The neck region is formed by mesenchyme from the paraxial (occipital region, floor of brain, facial muscle, dermis and meninges caudal to prosencephalon) and lateral plate mesoderm (laryngeal cartilages and CT in this region), neural crest (form midfacial and pharyngeal arch skeletal structures) and a thickened region known as the ectodermal placodes (5th, 7th, 9th and 10th cranial sensory ganglia). The arches are formed in the 4th to 5th week and are also called branchial arches. First they are mesenchymal tissue separated by pharyngeal clefts, which later pharyngeal pouches will develop on the lateral wall of the pharyngeal gut. All this is similar to gills. They contribute to the formation of the neck and face. The face appears at the end of 4th week, the stomodeum surrounded by the first pair of pharyngeal arches. Later the mandibular, maxillary, frontonasal and nasal prominence can be seen. The pharyngeal arches consist of a core of mesenchymal tissue covered by ectoderm and endoderm. They also contain a large number of neural crest cells which will form the skeletal parts of the face. Each arch has its own cranial nerve and arterial component, and they will carry this nerve and artery to wherever they migrate. 1st pharyngeal arch – consists of the dorsal portion of the maxillary process and ventral portion of the mandibular process, which contains Merkel's cartilage. Merkel’s cartilage will disappear with further development and form the incus and malleus. Maxillary process mesenchyme gives rise to maxilla, zygomatic and temporal bone. Muscles formed from the first arch are the muscles of mastication, digastric, mylohyoid, tensor tympani and tensor palatini. The nerve supply is the mandibular nerve of CN V. 2nd pharyngeal arch – The cartilage of this arch gives rise to the stapes, styloid process, stylohyoid ligament, lesser horn and upper part of body of the hyoid bone. But also forming the muscles: stapedius, stylohyoid, posterior belly of digastric, auricular and muscles of facial expression. And they are all supplied by the facial nerve. 3rd pharyngeal arch – The cartilage form the lower part of the body and greater horn of hyoid bone. Musculature forms the stylopharyngeus muscles which are innervated by the glossopharyngeal nerve. 4th and 6th pharyngeal arch – Fuse to form the thyroid, cricoid, arytenoids, corniculate and cuneiform cartilages. The levator palatine and constrictor pharyngeus muscles come from the 4th arch and are innervated by the superior laryngeal branch of the vagus. The recurrent laryngeal branch of vagus comes from the 6th arch. Pharyngeal pouches 1st pharyngeal pouch – Forms the tubotympanic recess and together with the 1st pharyngeal cleft forms the external auditory meatus, its distal portion forms the middle ear cavity and the proximal part forms the auditory tube, Lining of this later forms the tympanic membrane. 2nd pharyngeal pouch – Forms buds that penetrate the surrounding mesenchyme and invaded by mesodermal tissue. They will form the palatine tonsil which will later be invaded by lymphatic tissue. 3rd pharyngeal pouch – together with the 5th they form a dorsal and ventral wing. The dorsal wing of 3rd will form the inferior parathyroid gland and the ventral wing the thymus, which will migrate dorsally. 4th pharyngeal pouch – the dorsal wing will form the superior parathyroid gland which will attach itself to the migrating thymus. 5th pharyngeal pouch – Gives rise to the ultimobranchial body ad is later incorporated into the thyroid gland as the c cells. 8. The external features of the heart, the anatomy of the chambers and the structure of the valves. External features Has an apex in the 5th intercostal space about 9cm from the midline. The posterior aspect (base) is formed by the left atrium and partly by the posterior right atrium. Right border is formed by the SVC, right atrium and IVC, and the left border is formed by the left ventricle. The walls consist of endocardium, myocardium and epicardium. Outer there is a groove called the sulcus terminalis and it is during development the sinus venosus and internally this structure can be seen as the crista terminalis. The coronary sulcus marks the border between the atria and the ventricles. The interatrial line and interventricular line meats at this part and is called the crux. Chambers Right atrium – Formed by the atrium proper and the auricle (muscular pouch on upper anterior portion lined by pectinate muscles) and the sinus venarum (into which the venae cavae, coronary sinus and anterior cardiac veins opens). It is larger than the left but has thinner walls. The crista terminalis (muscular ridge providing attachment for the pectinate muscles that stretches between the venae cavae) separates the atrium proper and the sinus venarum. The venae cordis minimae ends in the foramina venarum minimarum cordis. Fossa ovalis is an oval depression that is open during development. Upper margin of foramen ovale is the limbus fossa ovale. Its pressure is normally a little lower. Have the Eustachian and thebesian valves. Left atrium – Smaller and have thicker walls. Only a few pectinate muscles in the auricle. It the most posterior of the chambers. It receives the pulmonary veins which carry oxygenated blood form the lungs. Right ventricle – Major portion of the anterior surface of the heart. Within this we can find the trabecular carneae cordis which is anastomosing muscular ridges of myocardium. The papillary muscles are cone shaped muscles attached to the chordae tendineae. The contraction of these prevents the tricuspid from being everted and by this preventing regurgitation of blood. Conus arteriosus is the upper smooth walled triangular portion leading to the pulmonary trunk. Septomarginal trabeculae are the moderator band between the interventricular septum (mostly muscular but have a short membranous upper part) and the anterior papillary and it prevents overdistention. Carries the AV bundle. Left ventricle – It is divided into left ventricle proper and the aortic vestibule and it leads into the aorta. Contains two papillary muscles holding the bicuspid valve with the chordae tendineae. Has also got the trabeculae carnae cordis. Performs harder work and is therefore thicker and longer. Valves Pulmonary valve – Left third costal cartilage and is audible over 2nd intercostals space. Have three semilunar cusps that are concave when viewed from above. They are not attached to any cords. The edges are formed by lunules (thickened region) and the angle holds the thickened portion, the nodule. Open like pockets to catch the reversed blood flow. Aortic valve – Lies in the 3rd intercostals space. Close during ventricular diastole (second dub) and is similar to the pulmonary. Audible over the right 2nd intercostals space. Tricuspid valve – Right AV valve. Between the right atrium and ventricle opposite the 4th intercostals space. Is audible over the right lower part of the sternum. Has anterior, posterior and septal cusps attached to chordae tendineae. Closed during ventricular diastole. First lub. Bicuspid valve – Left AV valve or mitral valve. Lies between the left ventricle and atrium in the left half of the lover sternum. It has two cusps an anterior and a posterior. Closed slightly before the tricuspid. Audible over the left 5th intercostals space at midclavivular line. 9. The impulse-generating and impulse-conducting systems and the extrinsic innervation of the heart. The vessels of the heart. The anatomy of the pericardium. Histology of the heart. Innervation of the heart The conducting system of the heart consists of the SA node and the AV node together with the musculature. SA node is located anterolaterally deep to the junction of the SVC and the right atrium near the superior point of the crista terminalis. This is called the pacemaker of the heart and it is specialized cardiac fibres. It regulates and initiates impulses for the heart at approximately 70 beats per min. Excited by sympathetic innervation and inhibited by parasympathetic innervation. The Av node is smaller than the SA node and is found in the posteroinferior region of the interatrial septum near the coronary sinus. SA node impulse is passed to this node through the right atrium walls. Distributes the signal through the AV bundle. Sympathetic speeds up conduction and parasympathetic slow it down. At the junction of the membranous and muscular parts of the septum the AV bundle splits into right and left branches. Then it splits into subendorcardial branches supplying the papillary muscles and the walls of the ventricles. The heart is innervated by nerve fibres from the cardiac plexus. This plexus is divided into deep and superficial portions. It can be found on the anterior part of the bifurcation of the trachea. It gives both parasympathetic and sympathetic innervation. Sympathetic presynaptic innervation comes from the inferomedial cell columns of the superior 5-6 thoracic segments of the spinal cord (cervical, superior thoracic paravertebral ganglia of the sympathetic trunks). Postsynaptic innervation comes form the cardiopulmonary splanchnic nerves. Cause Adrenergic innervation on the β2-receptors. Parasympathetic innervation is from presynaptic fibres from the vagus nerve. Postsynaptic can be found in the intrinsic ganglia in the walls of the heart. It acts via acetylcholine on the muscarinic receptors. Vessels of the heart The coronary arteries arise from the aorta and are filled during ventricular diastole. The Right coronary artery arise from the right aortic sinus, it supplies the right atrium and ventricle. This artery gives rise to the sinuartrial nodal artery (encircles the base of SVC after passing between the ascending aorta and right atrium), marginal artery (supplies inferior margin of the right ventricle), Posterior IV artery (supplies septum, left ventricle and AV node) and AV nodal artery. The left coronary artery arises from the left aortic sinus and gives rise to the anterior IV artery (septum and apex) and the circumflex artery (left atrium and left ventricle, and anastomose with the terminal branch of the right coronary artery). The coronary sinus is the largest vein of the heart and is situated in the coronary sulcus. Opens between the opening of IVC and AV. It receives the other veins of the heart. The great cardiac vein begins at the apex of heart. Middle cardiac veins also begins in the apex of heart but ascends in the posterior IV groove. Small cardiac vein runs on the right margin. Oblique vein of left atrium, anterior cardiac vein (anterior right ventricle) and the small cardiac veins which empties directly into the chambers are also found on the heart. Lymphatics of the heart follow the right coronary artery and empty into the anterior mediastinal nodes or follow the left coronary artery and empty into the tracheobronchial nodes. Pericardium It is a fibrouserous sac enclosing the heart and the roots of the great vessels. It can be found in the middle mediastinum. The fibrous part blends with the adventitia of the vessels and the central tendon of the diaphragm. The serous layer is further divided into a parietal and a visceral layer lining the fibrous respectively the heart. The cavity between these is the pericardial cavity. The pericardium forms two sinuses the transverse and the oblique. The transverse is posterior to the aorta and pulmonary trunk; a finger can be passed through. The oblique is found behind the heart surrounded by a reflection of the serous pericardium. Innervation: phrenic, vagus nerve and the sympathetic trunks. Blood supply: pericardiophrenic, bronchial and oesophageal arteries. Histology of the heart Cardiac muscle develops from splanchnic mesoderm. These cells are tightly bound together forming bundles. They are 15μm in diameter and 85-100μm in length. Similarily to the skeletal muscle they have cross-striations. But each cell has a nucleus; they are not multi nucleated like skeletal muscle is. The muscle is surrounded by and endomysium (CT sheath rich in capillaries). The intercalated discs are junctional complexes between adjacent muscles. It has a lateral and a transverse portion. The transverse consisting of facia adherens and desmosomes. The lateral mainly consists of gap junctions. The T tubules are more numerous in cardiac muscle and are found at the Z band and the sarcoplasmic reticulum is not as well developed. They contain numerous mitochondria and they use mainly fatty acids as the energy source for the heart. Atrial heart muscle contains fewer T tubules and has granules containing atrial naturetic factor, otherwise they are essentially the same as the ventricular. The heart has a fibrous skeleton which is responsible for the origin and insertion of cardiac muscle. The skeleton consists of septum membranaceum, trigona fibrosa and annuli fibrosi. These structures are all made of dense CT. The heart, just as the vessels are divided into 3 layers. The first is the endocardium which is a singe layer of squamous endothelial cells on a subendothelial layer of loose CT. The next layer the myocardium is the middle layer and the thickest. It consists of the heart muscle. It is arranged in a complex spiral. The final layer the epicardium is a thin layer of simple squamous cells supported by a layer of CT. This final layer can also be named as the visceral layer of the serous pericardium. The valves consist of dense CT lined by endothelium. 10. The development and malformations of the heart Development It is formed in the third week. The progenitor cells can be found in the epiblast lateral to the primitive streak which they will migrate through. Blood islands will also form which will later form the vessels and a tube, these islands are called the cardiogenic field. When the brain grows this will pull the buccopharyngeal membrane and move the heart cavity in place. The heart will during this expand and form a tube with an inner endothelial lining and an outer myogenic lining. The caudal portion will receive venous blood and the cranial arterial blood. It will slowly bulge more and more into the pericardial cavity, but still attached to the dorsal side of it. When the dorsal mesocardium disappears it will form the transverse sinus, suspending it into the cavity. The myocardium will thicken and mesothelial cells of the transverse septum will form most of the epicardium. The three layers of the heart are now formed. The heart tube will bend on the 23 rd day. The cephalic portion will bend ventrally, caudally and to the right. The caudal part will bend dorsocranial and to the left. This will be done by day 28, cardiac loop is formed. A common atrium is formed and an atrioventricular canal is formed. Bulbus cordis will form the trabeculated part of the third ventricle, conus cordis will form the outflow tracts and the truncus arteriosus will form the roots and proximal portions of the aorta and pulmonary vessels. A primitive right and left ventricle will be formed. Sinus venosus – receives blood form the right and left horn which in turn receives blood form the vitelline vein, umbilical vein and the common cardinal vein. During the 4th and 5th week this will become less open because of a shift in left-to-right shunts of blood. When the blood vessels are obliterated all that is left of the left sinus horn is the oblique vein of the left atrium and the coronary sinus. The right horn still communicates. This will form the sinus venarum of the right atrium and valvular folds will flank the sinuatrial orifices. The superior one will disappear and the inferior will develop into the valve of IVC and valve of the coronary sinus. Left venous valve and the septum spurium will form the atrial septum. Cardiac septa – These are formed by actively growing masses of tissue until they reach each other and fuse. Can also occur by one growing mass reaching the other wall. These masses, endocardial cushions will form in the atrioventricular region and cunotruncal region. Will form the septa, atrioventricular canals and valves and aortic and pulmonary canals. Can also be formed by a growth of a cavity within a wall due to an outer wall growing faster. They will eventually fuse. This type of septa partially divides the atria. Crest grows in the common atria at week 4 forming septum primum. The cushions will extend along this septum primum and form septum, an ostium will be formed through will blood can flow. The foramen ovale. This will disappear when the venous valve and the septum spurium fuses with the wall. The remaining part of the septum primum disappears a small part will stay and act as the valve of the foramen ovale. Atrioventricular septum will be formed by a superior and an inferior cushion. The blood can still pass freely as two lateral cushions are also formed. The superior and inferior will expand into the lumen and form a full wall. The valves are formed in the orifices by mesenchymal tissue and at first held in place by muscular cords but this are later replaced by dense CT. Interventricular foramen will be closed by the development of cunotruncal ridges. The left and tight conus cushions will proliferate together with the inferior endocardial cushion. They will twist around each other closing the interventricular foramen and forming the membranous part of the interventricular foramen. Ventricular septum will be formed by the expanding medial walls of the ventricles becoming apposed and gradually merge. The semilunar valves first appear as small tubercles on the truncus swellings. They will hollow out their upper surface to form the valves. Malformations Dextrocardia – heart on the right side instead of left. Can occur in situs versus or heterotaxy. Atrial and ventricular defects – the endocardial cushions are not developing right. Because of the neural crest cells is a part of the septum, there is often craniofacial defects as well if it is a genetic disorder. Probe patency – the septum primum and the septum spurium and left venous valve does not fuse. Holt-Oram syndrome – a genetic defect where the limbs are not developed correctly as well as the septum of the heart. Autosomal dominant trait. Atrial septal defects – can be due to the ostium secundum is larger than normal due to increased cell death or inadequate development of septum secundum. (cor trioculare biventriculare) Premature closure of oval foramen – massive hypertrophy of right atrium and ventricle. Ostium primum defect – the endocardial cushions do not fuse and form a proper cross. Forming an atrioventricular canal. Tricuspid atresia – obliteration of the right atrioventricular orifice. Absence or fusion of the tricuspid valves. Ventricular septal defect – most common malformation, due to membranous part of septum not fully developed. Teratology of Fallot – the septum does not form in the right place, giving larger or smaller chambers. Persistent truncus arteriosus – cunotruncal ridges fail to fuse. Transposition of the great vessels – the cunotruncal septum fails to follow its normal spiral course. Valvular stenosis – fusion of the valves. 11. The histology of the vessels; the fine structure of the capillaries. The development of the arteries and veins Histology All vessels generally have the same structural plan, but there are variations between the different types of vessels. The following layers are found: Endothelium – is a specialized layer of epithelial cells that mediate nutrition and waste transport across the vessels but also conversion of different hormones, lipolysis and production of different vasoactive substances. Tunica intima – one layer if endothelial cells supported by a subendothelial layer of loose CT (may contain smooth muscle). Between the intima and the media there is an internal elastic lamina in the arteries. This is composed of elastic lamina with fenestrae. Tunica media – consists of concentric layers of helically arranged smooth muscle. Between these elastic fibres and lamellae, reticular fibres, proteoglycans and glycoproteins can be found. This is produced by the smooth muscle cells. In arteries there is an external elastic lamina separating this layer from the adventitia. Adventitia – consists of collagen and elastic fibres. This layer gradually becomes continuous with the CT of the organs which it runs into or around. Vasa vasorum – Larger vessels need a blood supply them selves, this is the vasa vasorum. These are arterioles, capillaries and venules that can be found in the adventitia or the media. These vessels are more frequent in veins than in arteries. Innervation – Mainly unmyelinated sympathetic fibres that end in the adventitia. The neurotransmitters have to diffuse into the media to affect the smooth muscles. Except in the veins, which the nerves end in both the media and adventitia. Large elastic arteries – Help to stabilize blood flow, include the aorta and its large branches. Tunica intima is thicker than in muscular arteries. There are also more elastic fibres in the tunica media layer. Finally the adventitia is fairly underdeveloped. Muscular arteries – Control the affluence of blood by relaxing or contracting the smooth muscle. The subendothelial layer is thicker than in the arterioles. The internal elastic lamina is more prominent and the media is thick, up to 40 layers. Arterioles – Less then 0,5 mm in diameters and have narrow lumens. The internal elastic lamina may be missing; the media is not thicker than 2 layers. The adventitia is very thin. Capillaries – composed of a single layer of endothelial cells and diameter is not more then 7-9 μm. The endothelial cells are elongated in the direction of blood flow and pericytes can be found around them. These cells are thought to have contractile function. Capillaries can be of 3 different types. Continuous (absence of fenestrae), fenestrated (several circular transsecellular openings limited by cell membrane and have a diaphragm, which is thinner than the membrane), discontinues sinusoidal capillaries (the endothelial cells are separated from each other by a cleft, multiple fenestrations without a diaphragm). Venules – they are characterized by the presence of pericytes, have a very thin subendothelial layer. Muscular veins – have a few smooth muscle cells in their walls, irregular or collapsed lumen, the media consists of few smooth muscle cells with its reticular network and elastic fibres and the adventitia is well developed. The veins have valves in them consisting of 2 semilunar folds of the tunica intima, composed of CT with elastic fibres. The development of vessels Vessels develop through 2 processes, vasculogenesis (vessels arise from angioblasts) or angiogenesis (sprouting of vessels from pre-existing vessels). Arterial systems – Each pharyngeal arch have its own arterial supply and bring about its own vessels. The aortic arch arises from the aortic sac. They terminate in the right and left dorsal aortae, more caudally they form one vessel. The aortic arch will bind all the other segments together, creating 5 new pairs of arteries. These are simply numbered. These will modify and some will regress. The truncus arteriosus from which the aorta arises will divide into ventral aorta and pulmonary trunk. The aortic arch will also divide into the brachiocephalic artery and the aortic arch. The arches will obliterate but form different veins as they do this, maxillary from the first, hyoid and stapedial a. from the next second. The rest is still being formed (day 27). The 6th will become continuous with the pulmonary trunk but also form the ductus arteriosus during fetal life. The third will form the common carotid and the internal carotid artery; the external will sprout of this. The fourth will become the arch of the aorta and the left subclavian artery. Vitelline and umbilical arteries – they will fuse and form the mesenteric arteries of the gut including the celiac. The umbilical artery begins as a paired structure closely associated with the allantois. This will connect to the common iliac artery. And during development form the internal iliac and superior cervical vessels. Coronary arteries – angioblasts over the heart surface and the epicardium form these vessels. These will then grow into the aorta. Venous system – At the 5th week the vitelline, umbilical and cardinal veins can be seen. The vitelline will form the plexus around the duodenum (portal vein) and the hepatic veins will join it in the septum transversum. Forming the hepatic portion of the IVC. The right vitelline becomes the superior mesenteric. The umbilical pass by the liver and connecting to it, becoming the only one connecting the liver to the placenta. The ductus venosus forms between the left umbilical and right hepatocardiac vein, which after birth becomes the ligamentum teres hepatis and venosum. The cardinal veins consist of an anterior part draining the cephalic portion of the embryo and a posterior part draining the rest. These unite to form the common cardinal vein before entering the sinus horn. Several veins will be formed from this during the 5th week, the subcardinal (kidneys), sacrocardinal (lower extremities) and supracardinal (walls of the body) veins. The anterior cardinal veins will anastomose forming the left brachiocephalic vein, the right common cardinal vein and the proximal portion of the anterior right cardinal vein will form the SVC. Subcardinal anastomoses will form the left renal vein (left gonadal vein as well), left common iliac vein is formed by the sacrocardinal veins. 12. The fetal circulation and the circulatory changes at birth. Fetal circulation The blood from the placenta has about 80% oxygen saturation. The liver is bypassed by the ductus venosus which brings this blood directly into the IVC. Only small amounts enter the liver. This is regulated by a sphincter mechanism, it closes when the venous return is too high. The blood brought back to the heart where it goes through the oval foramen into the left atrium. Desaturated blood also enters from the lungs and blood enters the left ventricle and the ascending aorta. The heart musculature and brain is well supplied. The blood after deoxygenation enters the descending aorta and then into the two umbilical arteries. Circulatory changes These changes are caused by the beginning of respiration and the lack of placental blood flow. The ductus arteriosus closes of and this will increase the blood flow trough the lungs. Left atrial pressure will rise and right will decrease (no incoming placental blood). The oval foramen closes. Umbilical arteries close, umbilical vein and ductus venosus closes, Ductus arteriosus (bradykinin) closes and finally the foramen ovale closes. This can be reversed and crying by the baby can cause cyanotic periods. 13. The anatomy and histology of the larynx Anatomy It is the organ of voice production and a part of the respiratory tract. Consists of a number of different cartilages. Thyroid cartilage – Single hyaline cartilage, it holds the structure that forms the Adams apple in males (laryngeal prominence). The oblique line serves as an attachment site for the pharyngeal constrictor, sternothyroid and thyrohyoid muscles. Cricoid cartilage – Single hyaline cartilage, shaped like a signet ring. It articulates with the thyroid cartilage and marks the end of the pharynx. Epiglottis – Single elastic cartilage and is shaped like a spoon. It is found behind the tongue and its lower end is attached to the back of the thyroid cartilage. Arytenoid cartilages – Paired elastic and hyaline cartilages. They are shaped like pyramids and articulate with the cricoid. The vocal process serves as attachment for the vocal ligament and vocalis muscle. The muscular process attach to the thyroarytenoid, lateral and posterior cricoarytenoid muscles. Corniculate cartilages – paired elastic cartilages that can be found on the apex of the arytenoids. These are enclosed within the aryepiglottic folds of the mucous membrane. Cuneiform cartilages – Paired elastic cartilages in the aryepiglottic folds anterior to the corniculate cartilages. Thyroid membrane - Extends from the thyroid to the medial surface of the hyoid bone. Middle thicker part is the middle thyrohyoid ligament. Pierced by the internal laryngeal nerve and superior laryngeal vessels. Cricothyroid ligament – cricoid cartilage to the thyroid cartilage and the vocal processes of the arytenoids. Vocal ligament – post. Surface of the thyroid cartilage to the vocal processes. Upper border of conus elasticus. Vestibular ligament – thyroid cartilage to the anterior lateral surface of the arytenoid cartilages. Conus elasticus – lateral portion of the fibroelastic membrane. Is formed by the cricothyroid, median cricothyroid and vocal ligaments. Vestibule – laryngeal inlet to the vestibular folds (from the thyroid cartilage to the arytenoids cartilages above the vocal ligament). Ventricles – vestibular folds to the vocal fold (Angle of the thyroid cartilages to the vocal process, important in voice production). Infraglottic cavity – Rima glottides to the lower border of the cricoid cartilage. Rima glottides – space between the vocal folds and arytenoid cartilages. Muscles: Cricothyroid, posterior cricoarytenoid, lateral cricoarytenoid, transverse arytenoid, oblique arytenoid, aryepiglottic, thyroarytenoid, thyroepiglottic and vocalis. Innervation: recurrent laryngeal nerve innervate all the intrinsic muscles except the cricothyroid (external laryngeal branch, X) and supplies sensory innervation below the vocal cord. Branches of into the inferior laryngeal nerve. The superior laryngeal nerve (X) divides into the internal (innervate the mucous membrane and taste buds) and the external (innervate the cricothyroid and inferior pharyngeal constrictor muscle) laryngeal nerve Arteries: Inferior and superior laryngeal arteries. Veins: Inferior and superior laryngeal veins. Lymphatic: Into superior deep cervical lymph nodes and inferior deep lymph nodes. Histology The larger cartilages are hyaline and the smaller are elastic cartilage. They keep the airways open and prevent food from entering into the trachea. They also participate in the production of sound. The epiglottis is a little special because it has a lingual and a laryngeal surface. The lingual and apical portion of the laryngeal surface is covered by stratified squamous ept. The laryngeal surface is ciliated pseudostratified columnar ept. Mixed mucous and serous glands can be found underneath the ept. The vocal ligament is formed by large bundles of parallel elastic fibres covered by stratified squamous ept. 14. The anatomy, blood supply and innervation of trachea, bronchial tree and the lungs (bronchoscopy and bronchography). Anatomy of the trachea and bronchial tree The trachea begins at the lower border of the cricoid cartilage and ends by the bifurcation. It is 915cm in length and has 16-20 incomplete hyaline rings that open posteriorly. The carina is the last ring before the bifurcation and it has a keel-like ridge separating the left and right bronchi. The right bronchus is shorter, wider and more vertical than the left main bronchus. Runs under the arch of the azygos and divides into 3 lobar bronchi. Finally these split into 10 segmental bronchi. The lobar bronchi that pass above the pulmonary artery are called eparterial and the ones that pass below are called hyparterial. The left bronchi runs inferior to the arch of the aorta, crosses the oesophagus and thoracic aorta and divides into two lobar bronchi. Then finally into 8-10 segmental bronchi. It is crossed by the arch of the aorta and the left pulmonary vein. Anatomy of the lungs The bases of the lungs rest on the surface of the diaphragm descend during inspiration. Right lung: It has an apex; it is larger and heavier than the left lung, but also shorter and wider. This lung is divided into 3 lobes. The upper, middle and lower lobes, they are separated by the oblique and horizontal fissures. Each of the lobes receives a bronchial artery. It has 3 lobar bronchi and 10 segmental bronchi. Grooves for subclavian, SVC, azygous arch, oesophagus and cardia. Receive the arteries and veins in the order of artery, bronchus and vein. Left lung: It is divided into an upper and a lower lobe by an oblique fissure. It receives two bronchial arteries. Has a lingual (tongue shaped portion). Have a cardiac impression, cardiac notch and grooves for oesophagus, aortic arch, thoracic aorta and cardia. It has two lobar bronchi and 10 segmental bronchi. The functions of the bronchopulmonary segments are that they are functional, anatomical and surgical units. The intersegmental pulmonary veins are surgical landmarks for removal of a segment without severe blood loss. Innervation: Parasympathetic (excitatory) and sympathetic (inhibitory) innervate smooth muscle and glands of the bronchial tree. Some sensory endings of vagal origin can also be found and they control the reflex control of respiration. Arteries: Pulmonary trunk – carries poorly oxygenated blood to the lungs from the conus arteriosus of the heart. Passes in front of the ascending aorta and bifurcates into left and right pulmonary artery. Has lower blood pressure than the aorta. Left pulmonary artery is shorter and narrower than the right. Arches over the left primary bronchus. Right pulmonary artery runs towards the hilus under the arch of aorta, behind ascending aorta and anterior to the right bronchus. Bronchial arteries come form the thoracic aorta and there is one for the right and two for the left. Supplies the nonrespiratory tissue. Veins: Pulmonary veins are intersegmental and leave the lung as 5 but there is only 4 entering the left atrium. The right upper and middle veins join together. They carry oxygenated blood. Bronchial veins: receive blood form the bronchi and empty into the azygous and hemiazygous. Lymphatic: pulmonary, bronchopulmonary, tracheobronchial, tracheal, bronchomediastinal and eventually to the thoracic duct. Bronchoscopy Bronchoscope is passed down the trachea to the main bronchi. The carina has a fairly definite edge and it is distorted it there is a bronchiogenic carcinoma that has metastasised. The mucous covering it is very sensitive and associated with the cough reflex. 15. The anatomy of the pleura. The histology of the lung and the pleura. The development of the respiratory system. The anatomy of the pleura It is a thin serous membrane consisting of parietal and visceral pleura. The parietal part lines the inner surface of the thoracic wall and the mediastinum. Costal, diaphragmatic, mediastinal and cervical parts. It is reinforced by Sibson’s fascia which is a part of the endothoracic fascia. 1st rib to 7th cervical vertebrae. It forms the pulmonary ligament which extends from the hilus of the lung as an armless sleeve; it ends in a free falciform border. Visceral part invests the lung and is insensitive to stretch; it has vasomotor and vagal origin fibres. Innervation: intercostals and phrenic nerves. It is very sensitive to pain. Arteries: internal thoracic, superior phrenic, posterior intercostal and superior intercostal arteries. Visceral pleura are supplied by the bronchial arteries. Pleural cavity is a space between the two parts of the pleura. Contains a fluid that lubricates the lungs and facilitates its movements. The pleura has recesses, the costodiaphragmatic recess (can accumulate fluids) and the costomediastinal recess. Histology of the lungs Respiratory bronchioles – is terminal bronchioles divided into two or more. Their walls are interrupted by small saclike alveoli. This portion is lined by ciliated cuboidal epithelium and Clara cells. But at the rim the bronchiolar epithelium becomes squamous alveolar type. Along these bronchioles the alveolar bronchioles become more and more. It will become called an alveolar duct. Sphincter like muscle is lodged between the alveoli. It opens into the atria and communicates with the alveolar sac. These structures are all lined by elastic fibres. Alveoli are responsible for the spongy structure of the lung, within them the oxygen and carbon dioxide are being exchanged. There is interalveolar septum in between them and consists of squamous epithelial cells, capillaries, reticular and elastic fibres. The lung epithelium consists of capillary endothelial cells, type I pulmonary cells (very thin cells with small pinocytic vessels that may be important in the turnover of surfactant) and type II pulmonary cells (large rounded cells, which produce surfactant). There are also lung macrophages (dust cells). Blood-air-barrier – basement membrane of alveolar cells, fused basal lamina of alveolar and laminar cells, and the cytoplasm of the endothelial cells. Finally the surfactant. Histology of the pleura It is a serous membrane covering the lungs. Both membranes are composed of mesothelium resting on a fine layer of connective tissue containing collagen and elastic fibres. Air and liquid can enter the pleural cavity in pathological conditions. Development of lungs Trough the ventral foregut a lung bud grows out during the 4th week. The epithelium lining the entire respiratory system all derive from endoderm. Muscular, cartilaginous and muscular tissue in the trachea and bronchi comes from the splanchnic mesoderm. When the tracheoesophageal septum develops the oesophagus and trachea and lungs are separated from each other in the foregut. Only communication is through the laryngeal orifice. The lung buds will form the trachea and the bronchial buds. They enlarge and form the bronchi. The lung buds will expand caudally and laterally into the body cavity. The primitive plural cavity will soon be filled with the expanding lung buds and it will develop into the two layers of the pleura. The bronchi will divide and further develop into the segmental bronchi. Additional 6 divisions will occur before lungs are fully developed. The lungs can be used as lungs when the cuboidal cells of the respiratory bronchioles are changed to the pulmonary cells. They associate with blood and lymph capillaries in the primitive alveoli. During the 7th month the lung can be used. The lungs will in postnatal life continuously expand and increase for some years. The mature alveoli will not be seen before birth and the amount of surfactant will increase just 2 weeks before birth. During fetal development the foetus breathes amniotic fluid. Air into the lungs after birth is what will make them expand. 16. The anatomy, blood supply and histology of the nose and the nasal cavity. The paranasal sinuses. Anatomy of the nose Dorsum of nose expands from the apex to the root. It has two perform openings, which are bound by the alae. The cartilaginous part is covered by thick skin and the other parts by thin skin. The skin has many sebaceous glands. In the vestibule many hairs (vibrissae) can be found. The skeleton is made up of cartilage and some bone coming from the nasal bone, frontal process of maxillary bone and nasal part of frontal bone. The cartilage consists of two lateral, two alar cartilages and one septal cartilage. The septum consists of the vomer, perpendicular plate of ethmoid and the septal cartilage. Anatomy of the nasal cavity It communicates through the posterior opening (choanae) with the nasopharynx. The vestibule (dilated part) contains the hairs, sebaceous glands and sweat glands. Roof is formed by the nasal, frontal, ethmoid (cribiform plate) and sphenoid bones. The floor is formed by the palatine process of the maxilla and the horizontal plate of the palatine bone. Has the incisive foramen. Medal wall is the nasal septum. Lateral wall is formed by the superior and middle conchae of the ethmoid bone and the inferior conchae. Here the spenoethmoidal recess can be found (opens to the sphenoid sinus). Superior meatus (opening of the posterior ethmoidal cells), middle meatus (opening of the frontal sinus into the infundibulum, middle ethmoidal air cells on the ethmoidal bulla, and anterior ethmoidal air cells and the maxillary sinus in the hiatus semilunaris). Inferior meatus (opening of the nasolacriminal duct) and finally the sphenopalatine foramen (opening of the pterygopalatine fossa with the sphenopalatine artery and the nasopalatine nerve). Arteries: Lateral nasal branches of the anterior and posterior ethmoidal arteries of the ophthalmic artery. Posterior lateral nasal and posterior septal branches of the sphenopalatine artery of the maxillary artery, greater palatine branch of the descending palatine artery, and the septal branch of the superior labial artery of the facial artery. Nerves: Olfactory nerves for the olfactory mucosa. GSA sensation from the anterior ethmoidal branch of the ophthalmic nerve, nasal branches of the maxillary and alveolar branches of the infraorbital nerve. Paranasal sinuses Ethmoidal – ethmoidal air cells in the ethmoidal labyrinth. Frontal – Lies in the frontal bone, opens into the hiatus semilunaris of the middle nasal meatus. Supraorbital branch. Maxillary – Largest and lies on each side of the nasal cavity. Sphenoidal sinuses – Within the sphenoid bone and is innervated by the branches of the maxillary nerve. Pituitary gland can be reached through this sinus. They are involved in the reduction of weight and the resonance of voice. Histology Vestibule – Sebaceous and sweat glands. It has vibrissae and this is the part where the epithelium looses its keratinisation and become ciliated columnar/pseudostratified cells and brush cells (respiratory epithelium). Nasal fossae – Are covered by respiratory epithelium. Superior conchae are covered by olfactory mucosa which is ribbon like passages with swell bodies which are blood filled structures that decrease the flow of air. It also has olfactory chemoreceptors (bipolar neurons with 6-8 cilia) and epithelium (supporting cells and basal cells). Rich vascular network. The paranasal sinuses are lined with respiratory epithelium and contain few goblet cells. 17. The anatomy and the histology of the pharynx. Anatomy Nasopharynx – Can be found behind the nasal cavity above the oft palate and it communicates with the nasal cavity via the nasal chonchae. Pharyngeal tonsil is on the posterior wall. Connects the tympanic cavity via the auditory tube. Oropharynx – From the soft palate to the superior border of the epiglottis. The oropharyngeal isthmus communicates with the mouth. It contains the palatine tonsil which can be found in the tonsillar fossa and are bound by the palatoglossal and palatopharyngeal folds. The tonsil receives blood form the tonsillar branches of the facial artery, palatine branch of the maxillary and branches of the lingual artery. Innervated by the maxillary and glossopharyngeal nerves. Laryngopharynx – From the epiglottis to the lower border of the cricoid cartilage, it has a piriform recess. Other tonsils are the tubal tonsil (lymph nodules), lingual (lymph follicles on the dorsum of the tongue) and the Waldeyer’s tonsillar ring (around the oropharyngela isthmus). Muscles of the pharynx can be divided into the circular (superior, middle and inferior constrictor) and the longitudinal (stylopharyngeous, palatopharyngeous and salpingopharyngeous). Innervation: Pharyngeal plexus on the middle pharyngeal constrictor formed by the pharyngeal branches of the glossopharyngeal and the vagus. Arteries: Ascending pharyngeal, ascending palatine branch of facial, descending palatine, pharyngeal branches of the maxillary and branches of the superior and inferior thyroid arteries. Swallowing Bolus of food is pushed back by the tongue into the fauces. From there it is squeezed by the palatoglossus and palatopharyngeous into the oropharynx. Nasopharynx is closed. Walls of the pharynx are raised and the bolus passes over the epiglottis. Contractions of the constrictor muscles move the bolus into the oesophagus. Histology Nasopharynx – covered by respiratory epithelium containing goblet cells. The pharynx itself is covered by stratified nonkeratinized squamous epithelium. It also has small mucous salivary glands in its lamina propria. Palatine tonsil – lined by squamous stratified epithelium and forms a band with free lymphocytes and lymph nodes. It has 10-20 crypts. It is capsulated by dense connective tissue. Pharyngeal tonsil – It is covered by ciliated pseudostratified epithelium, contains pleats of mucosa and diffuse lymphoid tissue and nodules. It has no crypts and a thinner capsule than the palatine tonsil. Lingual tonsil – Small and numerous at the base of the tongue. Are covered by stratified squamous epithelium and each of them has a single crypt. 18. The development of the face, the oral and nasal cavities. Face At the end of 4th week the first pair of pharyngeal arches forms the maxillary, mandibular and frontonasal prominences. Thickenings of the surface ectoderm on the sides of the frontonasal prominence will form the nasal placodes (olfaction). The placodes will form the nasal pits and the ridge around these are the nasal prominence. Maxillary prominence will expand during 6 th and 7th week, the cleft between the medial nasal and the maxillary prominence will disappear, and they also together form the lip. The lateral nasal prominence is separated by the nasolacriminal groove which will grow into a tube and the lacriminal sac and the prominences will merge together. Maxillary prominence will form the cheeks ad the maxilla. The medial nasal prominence also merge together forming the labial component, the upper jaw component (teeth) and the palatal component, known as the intermaxillary segment. Intermaxillary segment form the nasal septum and the primary palate. The palate forms a horizontal plate in the 7th week and forms the secondary palate. Incisive foramen is the midline mark between the primary and the secondary plates. Nasal and oral cavity Nasal pits will deepen during the 6th week and the oronasal membrane separated it into an oral and nasal cavity. The primitive choanae will be formed. The formation of the secondary palate and the primitive nasal chambers will form the cavity and move the choanae. Paranasal sinuses develop as diverticula of the nasal wall. Contribute to the shape of the face. 19. The anatomy, histology and development of teeth. Anatomy Teeth consists of enamel (covering the crown), dentin (central pulp space) and pulp (fills the central cavity). The root is covered by cementum and where the cementum and enamel meet is called the cervix. The root is held in the alveolar bone by the periodontal ligament, which is fibrous CT with collagen. Each maxillary molar have 3 roots and each mandibular molar have 2 roots. There are incisors (for cutting with a single root), canines (for tearing and with a single root), premolars (two cusps for grinding, upper first bifid) and molars (3 cusps used for grinding). The deciduous teeth are 20 and the permanent 32, 2 incisors, 1 canine, 2 premolars and 3 molars in each quadrant. Innervation: maxillary teeth – anterior, middle and posterior-superior alveolar branch of the maxillary nerve, its gingiva on the outer surface by the same but also the infraorbital nerve. On the inner surface by the greater palatine and the nasopalatine nerves. Mandibular teeth – inferior alveolar branch of the mandibular nerve, the gingival are inner by the lingual nerves and outer the buccal and mental nerves Histology Dentin – calcified (70%) tissue harder than bone. The calcium salts are found in the form of hydroxyapatite crystals and dentil also contain collagen I, glycosaminoglycans, phosphoproteins and phospholipids. The organic matrix is secreted by the odontoblasts; these have processes that extend through the dentin. The processes become tubules in thicker dentin. Matrix vesicles from the odontoblasts facilitated the formation of hydroxyapatite crystals. Enamel – Hardest component of the human body contains 96% minerals. Mostly hydroxyapatite crystals. Ectodermal origin. The collagen fibres found in enamel are amelogenins and enamelins. The enamel is arranged in rods bound by interrod enamel. The matrix of the enamel is secreted by the ameloblasts, they have a process called Tomes’ process which contain the secretory granules. Pulp – Loose CT containing odontoblasts, fibroblasts, thin collagen fibrils and glycosaminoglycans. It is highly innervated and vascularized. Cementum – is similar to bone in composition but not structure. Apical region contain the cementocytes in lacunae. Alveolar bone - is of the immature bone type in which we cannot se the lacunae. The fibres from the form the Sharpy’s fibres that extend into the cementum. Perforating vessels. Gingiva – mucous membrane composed of stratified squamous epithelium and lamina propria. Development The teeth are developed from neural crest cells mesenchyme and the oral epithelium. Oral cavity forms a dental lamina (c-shaped) by the end of 6th week and gives rise to dental buds. Deep surface invaginates and forms the cap stage of tooth development. Now the outer and the inner dental epithelium are formed. The mesenchyme forms the dental papilla. The tooth will continue to grow and will look like a bell. Mesenchyme of the papillae differentiates into odontoblasts, remaining cells of the mesenchyme form the pulp. Inner dental epithelium forms the ameloblasts, enamel first forms at the apex. They will also leave a dental membrane on the outside of the tooth. The dental epithelium extends into the root and forms the root sheath. Mesenchymal cells in contact with the root will differentiate to cementoblasts. The teeth will continue to expand and occur 6-24 months after birth. 20. The anatomy, histology and development of the tongue. Anatomy It is attached to the hyoid bone, mandible, styloid process, palate and pharynx by muscles. The sulcus terminalis divides it into an anterior and posterior part. At the apex of the sulcus terminalis the foramen cecum can be found and is the origin of the embryonic thyroglossal duct. Lingual papillae and lingual tonsil can be found on the tongue. Innervation: The extrinsic and intrinsic muscles by the hypoglosseal nerve except for palatoglosseous which is innervated by the vagus nerve. Anterior part receives sensory innervation from the lingual nerve and taste sensation from the chorda tympani. Posterior part receives both from the glossopharyngeal nerve. Epiglottic region from the internal laryngeal branch. Arteries: Lingual artery from the external carotid artery and gives rise to the suprahyoid, dorsal lingual and sublingual arteries. Finally terminates as the deep lingual artery. Histology It is a mass of striated muscle covered by mucous membrane. The muscles cross each other in 3 planes. Filiform papillae – have elongated conical shape found over the entire tongue. No taste buds and it are keratinized. Fungiform papillae – resemble mushrooms. Contain scattered taste buds. Foliate papillae – poorly developed in humans, have parallel ridges. Circumvallate papillae – 7-12 large circular papillae in the sulcus terminalis region. Von Ebner’s glands drain their moats and provide continuous flow over the taste buds, but they also secrete lipase to remove remaining lipids in this region. Taste buds – Are onion shaped structures with 50-100 cells. The gustatory cell projects microvilli through a taste pore into the cavity. They are held by sustentacular cells and replaced by undifferentiated basal cells. Development It appears first after the 4th week in the form of 2 lateral and one medial lingual (tuberculum impar) swelling. They originate from the first pharyngeal arch. The second median arch, the copula is formed from the 2nd, 3rd, and 4th arch. The third median swelling from the posterior part of the 4th arch. The lateral swellings overgrow the tuberculum impar and form the anterior part of the tongue. The posterior part of the tongue comes from the 2nd, 3rd, and 4th pharyngeal arch. The epiglotteal part of the tongue is developed from the 4th arch. 21. The anatomy, histology and development of the major salivary glands. Anatomy Submandibular gland – It lies in the deep cervical fascia in the submandibular triangle, superficial to the mylohyoid muscle and between he hyoglossus and styloglossus muscle medially, and mylohyoid laterally. Wharton’s duct runs between the mylohyoid and the hyoglossus, medial and then superior to the lingual nerve, empties at the caruncule on the side of the frenulum of tongue. Innervation: parasympathetic secretomotor from the facial nerve in the chorda tympani and lingual nerve. Synapse with the submandibular ganglion. Sublingual gland – In the floor of mouth between the mucous membrane and the mylohyoid muscle. Surrounds the submandibular duct. Empties into the floor of the mouth along the sublingual fold through 12 short ducts. Innervation: secretomotor parasympathetic fibres form the submandibular ganglion through the lingual nerve. Histology Saliva is a fluid for digestion, lubrication and protection. Capsule of collagen fibres surrounds the glands. The secretory portion is branching tubules and secretory end pieces. Serous cells are pyramidal and often form acinus with a small lumen. Mucous cells are cuboidal to columnar with oval nuclei. Contains more glycogens and are often arranged in tubules. Serous demilunes are a cap of serous cells around a mucous tubule found in the submandibular and the sublingual glands. Several myoepithelial cells can be found around the tubules and ducts. The ducts empty into intercalated ducts which join together and form striated ducts. They will later become excretory or interlobular ducts. Parasympathetic innervation increase salivary production and excretion. Submandibular – Branches tubuloacinar gland with both mucous and serous glands. Serous glands are the main component. Demilunes secrete lysozyme; serous cells secrete fluid with amylolytic activity. Sublingual gland – This gland is also a mixed gland but mucous glands predominate. Development 22. The anatomy, histology and development of the oesophagus and the stomach. Anatomy Oesophagus – It is a muscular tube continuous with the pharynx in the neck and enters the thorax behind the trachea. It has 3 constrictions: where it begins at C6, crossing of the main stem bronchus and at T10 where it pierces the diaphragm. At the gastroesophageal junction there is an actual sphincter, the inferior oesophageal sphincter. The phrenicoesophageal ligament attaches it to the oesophageal hiatus in the diaphragm. The anterior surface is covered by peritoneum of the greater sac and the posterior surface by peritoneum of the omental bursa. Arteries: Inferior thyroid, bronchial and oesophageal arteries of t he aorta and the left gastric and the inferior phrenic arteries. Veins: portal venous system through the left gastric vein and the systemic venous system through the oesophageal vein which empties into the azygous vein. Innervation: oesophageal nerve plexus formed by the vagal trunk, thoracic sympathetic trunk, greater splanchnic nerves and periarterial plexus. Lymphatics: left gastric lymph nodes into the celiac lymph nodes. Stomach – Rests on the pancreas, spleen, left kidney, left suprarenal gland, transverse colon with mesocolon and the diaphragm. Entirely covered by peritoneum. It has a greater and a lesser curvature, cardiac and pyloric openings and finally cardiac and angular notches. It is divided into four regions, cardia, fundus, body and pylorus. Pylorus is further divided into antrum and sphincter (smooth muscle). Inner surface have rugae which in the lesser curvature forms a gastric canal. Produces hydrochloric acid, pepsin and gastrin. It can hold 2-3 litres. Arteries: right and left gastric, right and left gastroepiploic and short gastric arteries. Veins: Right and left gastric vein into the portal vein, short gastric veins and the left gastro-omental veins. Also a small pyloric vein. Lymphatics: Into the gastric, the pancreaticosplenic, pancreaticoduodenal or the pyloric lymph nodes. Innervation: parasympathetic from the vagal trunks, sympathetics from the T6-T9 greater splanchnic nerves. Histology Oesophagus - It is a muscular tube that transports food stuffs with peristaltic movements and relaxation of the internal oesophageal sphincter. It is covered by nonkeratinized squamous epithelium. It has the four layers found in the rest of the digestive tract, the mucosa, submucosa, muscularis and serosa. In the submucosa the oesophageal glands secreting mucous can be found. In the lamina propria near the stomach the oesophageal cardiac glands can be found. They also secrete mucous. It mainly contains of striated muscle near the pharynx, in the middle a mixture and near the stomach almost only by smooth muscle. The last part is the only part covered by serosa. Stomach – Mixed endocrine-exocrine organ. 3 histological parts. The surface epithelium (simple columnar secreting alkaline fluid) form gastric pits. Into these the gastric glands empty. The cardia contains cardiac glands producing lysozyme and mucous, but parietal cells can also be found in this region. Fundus and body has gastric glands with 3 distinct regions, isthmus, neck and base. The isthmus contains the stem cells, and the parietal cells (have intracellular canaliculi, lots of mitochondria and secrete HCl and gastric intrinsic factors for the absorption of B12), the neck contains mucous neck cells and parietal cells, the base has parietal, enteroendocrine cells (secrete serotonin) and zymogenic/chief (secrete pepsinogen which is turned into pepsin by the acidic environment and lipase) cells. Gastrin is secreted in the gastric mucosa and together with histamine they increase the secretion of HCl. The pylorus has deep gastric pits into which the pyloric glands open, these glands secrete mucous and lysozyme. Gastrin cells secrete gastrin, which stimulate gastric acid secretion. Enteroendocrine cells secrete somatostatin stimulating secretion of HCl. Development Oesophagus - In the 4th week the tracheoesophageal septum divides the lung buds from the dorsal structures of the foregut. This is the oesophagus; it will be lengthened by the descent of the lungs and heart. The muscular coat will be formed by surrounding mesenchyme. Upper part vagus nerve, lower splanchnic nerves. Stomach – It is at first a dilation of the foregut in the 4th week. The stomach will be positioned by rotating around and anteroposterior and a longitudinal axis (90 degrees). Making the vagus innervation to be at the anterior wall instead of the lateral wall. This rotation will form the lesser and greater curvature. It is attached to the walls by the dorsal and ventral mesogastrium. The movement of these during positioning will create the omental bursa. The greater omentum will be formed by the dorsal mesogastrium and the lesser and falciform ligament by the ventral mesogastrium. 23. The anatomy, histology and development of the small intestines. Anatomy Duodenum – It is a c-shaped tube, the shortest but the widest part of the small intestine. It is retroperitoneal except for the beginning. Connected to the liver by the hepatoduodenal ligament. It is divides into 4 parts; the first is the free section the duodenal cap, second part is where the common bile and pancreatic ducts open, the third is the longest and cross the IVC, aorta and vertebral column. Crossed by the superior mesenteric vessels and the fourth part is the end forming the duodenojejunal junction. It is fixed by the suspensory ligament. Jejunum – Proximal 2/5 of the small intestine, larger and thicker than the ileum. It has no plicae circulares, no Peyer's patches and windows to the mesenteric arteries. Less prominent arterial arcades than the ileum and longer vasa recta. Ileum – Longer than the jejunum and is found in the false pelvis. It has more mesenteric fat than the jejunum. Arteries: celiac and superior mesenteric arteries, gastroduodenal artery and superior and inferior pancreaticoduodenal artery. Veins: Follow the arteries and drain into the portal vein. Lymphatics: anterior lymphatic vessels into the pancreaticoduodenal lymph nodes. Posterior lymphatic vessels drain into the superior mesenteric lymph nodes. Innervation: celiac and mesenteric nervous plexuses from the vagus, greater and lesser splanchnic nerves. Histology The mucosa is formed into plicae circulares, but they are not a significant feature in the duodenum and the ileum. Intestinal villi grow out from the mucous and between these the glands of Lieberkühn grow out. The villi are covered by simple squamous epithelium. The glands contain a few different cells such as absorptive cells/enterocytes with a brush border and a thick glycocalyx protecting them. Goblet cells are acid glycoprotein (mucin) producing cells. Paneth’s cells are exocrine cells secreting lysozyme. M cells are epithelial cells overlying the Peyer’s patches, endocytose antigens. There is also an endocrine system suspected to secrete molecules that enhance or increase the activity of other secretions of the cells of the small intestines. Each villus will receive an artery from the plexus in the submucosa. There are also smooth muscles in the villi and this is responsible for the rhythmic movements of them. The innervations are of intrinsic and extrinsic components, the intrinsic are the myenteric nervous plexus between the outer longitudinal and inner circular muscular layer and the submucosal plexus. Duodenum – The villi are broad, tall and numerous. They have few goblet cells and duodenal glands can be found in the submucosa secreting mucous (alkaline). Jejunum – Fewer villi and shorter. More goblet cells are found. Ileum – Contains few villi that are even shorter and narrower. It has the largest amount of goblet cells and many lymphatic nodules. They are found in the lamina propria and the submucosa and are called Peyer’s patches. Development Duodenum – The terminal part of the foregut and the cephalic part of the midgut form the duodenum, distal to the lung buds. The duodenum rotates with the stomach and acquires its c-shaped form. The dorsal mesoduodenum will fuse with the peritoneum and fix it in a retroperitoneal position. Jejunum – The cranial end of the midgut will elongate and form a loop; this will become part of the duodenum, the jejunum and part of the ileum. It will rotate around an axis formed by the superior mesenteric artery, counterclockwise by 70 degrees. The jejunum and ileum will continue to elongate during this rotation and form a coiled pattern. 24. The anatomy, the histology and the development of the large intestines. Anatomy It is approximately 1,5 meters long. Absorb water, salt and electrolytes. Colon – Ascending and descending are retroperitoneal, transverse and sigmoid are intraperitoneal. It has teniae colli which are narrow bands of the outer longitudinal muscular coat, haustra are outpocketings which are produced by the teniae and epiploic appendages which are fat sacs arranged in rows along the teniae. Innervation: ascending and transverse by vagus, descending and sigmoid by pelvic splanchnic nerves. Arteries: Ascending and transverse by the superior mesenteric, descending and sigmoid by the inferior mesenteric. Lymphatics: Superior and inferior mesenteric nodes. Cecum – Blind pouch of the large intestine lying in the right iliac fossa. Appendix – narrow and hollow muscular tube with lymphoid tissue, suspended in the mesoappendix. Lies in the lateral third of a line drawn between the umbilicus and the right anterior superior iliac spine. Histology Mucosal membrane with no villi. Intestinal glands are long with numerous goblet and absorptive cells and only a small number of enteroendocrine cells. Absorb water, form fecal mass and produce mucous. The lamina propria is rich in lymphoid cells and nodules. The difference from the small intestine when it comes to the muscularis layer is that the longitudinal layer of the colon is in the form of 3 longitudinal bands the teniae colli. Appendix – abundant lymphoid follicles, with a small, narrow lumen. Fewer and shorter intestinal glands. Development The caudal end of the midgut will form the rest of the ileum, cecum, appendix, ascending colon and a part of the transverse colon. From the caudal loop a cecal bud emerges and it will descend into the right iliac fossa placing the hepatic flexure and ascending colon on the right side of the abdominal cavity. Distal portion of the cecal bud will form the appendix. The hindgut gives rise to the distal third of the transverse colon, descending colon and the sigmoid. 25. The anatomy, histology and development of the rectum and the anal canal. Anatomy Rectum – It follows the curvature of the sacrum and the coccyx. The lower dilated part for storage of faeces is called the ampulla. It has peritoneal covering on the anterior, right and left sides on the upper third part, only on the front on the middle part and no covering on the lower third. It has three permanent folds created by circular muscular folds, the Houston’s valves. Arteries: Superior, middle and inferior rectal arteries and the middle sacral artery. Veins: superior rectal and caval venous system (via middle and inferior rectal) to the portal system. Innervation: Parasympathetics from the pelvic splanchnic nerves. Sympathetic form the lumbar splanchnic nerves and the hypogastric plexus. Lymphatics: pararectal nodes into the inferior mesenteric or sacral lymph nodes. Anal canal – It is divided into two parts a visceral and a somatic portion separated by a pectinate line. It has anal columns (longitudinal folds of its upper mucosa), anal valves (crescent shaped folds at the lower end), anal sinuses (pouch like recesses at the lower end, anal glands open into these) and internal and external anal sphincter circular smooth respectively skeletal muscle. Veins: Above the pectinate line into the superior rectal vein to the portal venous system. Below into the middle and inferior rectal veins into the caval system. Lymphatics: Into the internal iliac nodes above the line and below into the superficial inguinal nodes. Innervation: sensory above the line by the pelvic plexus, below the line by the somatic fibres of the pudendal nerves. Histology Rectum - Lined by simple columnar epithelium, striated borders ad goblet cells. It has intestinal glands, adipose cells and lymphatic nodules in the lamina propria. The longitudinal folds are the core of the submucosa. The teniae coli extend down and between the inner circular and outer longitudinal layer the parasympathetic ganglion of the myenteric plexus can be found. The adventitia covering it has numerous arterioles and venules, but these can also be found in the submucosa. Anal canal - The junction has the transition from simple columnar epithelium and stratifies squamous epithelium. The muscularis mucosa terminates in the region of this junction and the lamina propria is replaced by dense irregular CT. The submucosa becomes highly vascularized by the internal haemorrhoidal plexus. Smooth muscle forms an internal anal sphincter and skeletal muscle an external anal sphincter. Divided by the Hilton’s white line. Development The terminal portion of the hindgut posterior to the cloacae forms the anorectal canal. It is an endoderm lined cavity with ectoderm coverage, divided by the cloacal membrane. The cloacal membrane creates and opening for the hindgut at week 7. The ectoderm in this region will proliferate and therefore the caudal part of the anal canal will be of ectodermal origin. The line between the endoderm and the ectoderm is the pectinate line. 26. The anatomy, histology and development of the liver. Anatomy It is the largest organ in the body and is important in bile production and secretion and detoxification of the blood. It also stores carbohydrates, perform protein synthesis and produce heparin and bile pigments. It is surrounded by peritoneum and attached to the diaphragm by the coronary and the falciform ligaments and right and left triangular ligaments. The bare area can be found on the diaphragmatic surface. Portal triad – portal vein, hepatic artery and bile duct. ChoVA. Right lobe – anterosuperior, anteroinferior, posterosuperior and posteroinferior segments. Left lobe – Medial and lateral segments each divided into superior and inferior segments. Medial superior= caudate lobe (blood from both hepatic arteries and bile into both hepatic ducts), medial inferior = quadrate lobe (blood only into the left hepatic artery and bile into the left hepatic duct). Fissures and ligaments – H-shaped, ligamentum teres hepatis, fissure for ligamentum venosum, fossa for gallbladder, fissure for IVC and porta hepatis (hepatic duct, artery, nerves, lymphatics and portal vein). Arteries: oxygenated blood from the right and left hepatic from the common hepatic which originates from the celiac trunk and deoxygenated nutrient rich from the portal vein. Veins: Portal vein into the IVC. Lymphatics: superficial and deep lymphatics follow the portal triad into the hepatic lymph nodes, then into the celiac lymph nodes and finally into the cisterna chyli. Innervation: Hepatic plexus from sympathetics from the celiac plexus and parasympathetics from the vagal trunks. Histology The liver is covered by a CT capsule (Glisson’s capsule). The lower lobule is the structural component of the liver hepatocytes. Polygonal structure with the portal space at the periphery and a central vein in the centre. Postal spaces consist of a bile duct, lymphatics, nerves and blood vessels. The hepatocytes in this structure are arranged like bricks on a wall and the spaces between them are called the sinusoids. Another space that can be found is the space of Disse, a space separating the hepatocyte from the endothelial cell. It permits easy exchange of molecules. The sinusoids also contain Kupffer cells which are the macrophages of the liver. Portal vein supply – portal venoules – distributing veins – inlet venules – sinusoids – central vein – sublobular vein – hepatic vein. Arterial system – hepatic artery – interlobular artery – sinusoids – central vein. Each hepatocyte is in contact with the space of Disse, and sometimes two hepatocytes hold bile canaliculi in between them. Bile flow from the centre to the periphery entering the Herring’s canals which will enlarge and form the right and left hepatic duct. The hepatocyte stain intensely and they are basophilic. The liver has an extraordinary capacity for regeneration. Development It is the outgrowth of the endodermal epithelium of the distal foregut. The liver bud will rapidly increase and pierce the septum transversum. The bile duct is created from the narrowing of the connection between the developing duodenum and the liver. This bile duct will form a small outgrowth that will form the gallbladder. The hepatic sinusoids are formed from the vitelline and umbilical cords. The haematopoietic, Kupffer and CT cells of the liver is derived from the mesoderm of the septum transversum. The septum transversum become the lesser omentum and the falciform ligament. 27. The anatomy, histology and development of the pancreas Anatomy It forms the major portion of the stomach bed and is retroperitoneal except for its tail which lies in the lienorenal ligament. The head is within the bend of the duodenum and the head has an uncinate process to the left behind the superior mesenteric vessels. The exocrine part produce digestive enzymes and the endocrine part produce insulin and glucagons. The main pancreatic duct (Wirsung) runs from the tail along the pancreas, joins with the bile duct and empties on the hepatopancreatic ampulla before entering the duodenum at the greater papilla. The accessory duct (Santorini’s) begins at the head and empties on the lesser duodenal papilla. Arteries: Branches of the splenic artery, superior and inferior pancreaticoduodenal arteries. Veins: splenic vein or the superior mesenteric. Lymphatics: pancreaticosplenic lymph nodes draining into the superior mesenteric or celiac lymph nodes. Innervation: vagus and abdominopelvic splanchnic nerves. Parasympathetic and sympathetic via the celiac and superior mesenteric plexus. Histology The endocrine portion is the islets of Langerhans and the exocrine portion is the compound acinar glands. This gland is made up of several serous cells surrounding a lumen. These cells are supported by reticular fibres and they are arranged into lobules by septa emerging into the pancreas from the CT covering. The exocrine pancreas secretes: 1,5-3 L of fluid containing water, ions, proteases, lipases, amylase, phospholipase A2 and nucleases. The secretion of this is controlled by the hormones secretin and cholecytokinin, but also by the parasympathetic stimulation via the vagus nerve. The islets of langerhans are rounded clusters of cells found in the exocrine pancreas. They are surrounded by a capsule of reticular fibres. There are 4 types of cells, A (producing glucagons), B (producing insulin), D (producing somatostatin) and F (producing pancreatic polypeptide) Development The pancreas is formed by the dorsal and ventral bud of the endodermal lining of the developing duodenum. The ventral part will move to a position below the dorsal when the duodenum moves with the stomach and it will form the lower part and the uncinate process. The main pancreatic duct will be formed by the distal part of the dorsal pancreatic duct and the bile duct, the proximal part of this becomes the accessory pancreatic duct. Islets of Langerhans develop during the 3rd month from parenchymatous pancreatic tissue. 28. The layers, duplicatures and recesses of the peritoneum. Layers It is a serous membrane lined by mesothelial cells. It consists of a visceral and a parietal layer. The visceral layer covers the organs of abdomen and is innervated by its autonomic nerves. The parietal layer lines the abdominal and pelvic walls and is innervated by the somatic nerves. Duplicatures/reflections/folds Lesser omentum – double layer of peritoneum from the porta hepatis to the lesser curvature of stomach. Consists of the hepatogastric and hepatoduodenal ligaments. Between its two layers the right and left gastric vessels run on the lesser curvature. The right free margin contains the proper hepatic artery, the bile duct and the portal vein. Greater omentum – Hangs like an apron over the greater curvature of the stomach covering the transverse colon. It usually plugs any herniations, adheres to inflamed areas ad wrapping around them. It has protective function. It transmits the right and left gastroepiploic vessels on the greater curvature. Contains the gastrolienal ligament (greater curvature to hilus of spleen), lienorenal ligament (hilus of spleen to right lung), gastrophrenic (greater curvature to the diaphragm) and the gastrocolic ligament (greater curvature to the transverse colon). Mesentery of small intestine – double fold of peritoneum suspending the jejunum and ileum, transmitting blood vessels to and from these structures, such as the superior mesenteric and intestinal vessels, nerves and lymphatics. Begins at the duodenojejunal flexure to the right iliac fossa. Transverse mesocolon – transverse colon to the posterior abdominal wall forming the gastrocolic ligament with the greater omentum. Contains middle colic vessels, nerves and lymphatics. Sigmoid mesocolon - sigmoid colon to the pelvic wall containing the sigmoid vessels. Mesoappendix – appendix to the mesentery of the ileum. Other peritoneal ligaments – phrenicocolic, falciform, ligamentum teres hepatis (remnant of left umbilical), coronary ligament, ligamentum venosum (remnant of ductus venosus). Folds – medial, lateral and median umbilical folds, rectouterine fold and ileocecal fold. Cavities It is the space between the two layers of the peritoneum containing a fluid that facilitates the movement of the viscera. Lesser sac (omental bursa) – irregular space behind liver, lesser omentum, stomach and upper part of greater omentum. Communicates with the greater sac through the epiploic foramen. It has 3 recesses, superior behind stomach and lesser omentum, inferior behind stomach and upper part of greater omentum and the splenic recess behind the hilus of spleen. Greater sac – extends from the diaphragm and the pelvic floor. Its recesses are the subphrenic between the liver and the diaphragm, subhepatic between the liver and transverse colon, hepatorenal between the liver and kidney and finally the paracolic laterally to ascending and descending colon. 29. The lymphatic drainage and lymph nodes of the visceral organs of the abdominal cavity. Parietal lymph nodes Left and right lumbar lymph nodes – Situated along the abdominal aorta, nodes situated further down drain into these, but also nodes form the suprarenal gland, kidney, urether, testis, ovary, uterine tubes, fundus of uterus and abdominal wall. They drain mainly into the lumbar trunk and can be divided into lateral aortic, pre-aortic and postaortic lymph nodes. Intermediate lymph nodes – It is a group situated between the inferior vena cava and the aorta, drain like the right and left lumbar lymph nodes. Inferior phrenic lymph nodes – Nodes situated along the inferior surface of the diaphragm near the aortic opening. Inferior epigastric lymph nodes – 3-4 nodes along the inferior epigastric artery, they receive lymph from the supply area of the artery. Visceral nodes Celiac lymph nodes – Nodes situated near the celiac trunk, form the secondary filter for the stomach, duodenum, liver, gallbladder, pancreas and spleen. They drain into the cisterna chyli or the intestinal trunk. Right and left gastric lymph nodes – follow the course of the right and left gastric arteries on the lesser curvature of the stomach. Receives lymph from stomach and drains into the celiac lymph nodes. Gastro-omental lymph nodes – situated at the greater curvature of stomach along the gastro-omental arteries. They drain the stomach and the greater omentum and empty into the lymph nodes of the liver on the right and on the left into lymph nodes of the spleen and pancreas. Pancreatic lymph nodes – convey their spleen to the celiac lymph nodes and are situtated at the hilus of the pancreas. Pancreaticoduodenal lymph nodes – Small nodes between the pancreas and duodenum. Drain pancreas and duodenum. Splenic lymph nodes – Nodes near the hilum of the spleen draining into the celiac lymph nodes. Hepatic lymph nodes – Nodes at the hilum of the liver and the hepatoduodenal ligament. Transport lymph to the celiac lymph nodes. Mesenteric lymph nodes – drain the mesentery and are numerous. Drain into the celiac lymph nodes. Ileocolic, prececal, retrocecal and appendicular lymph nodes – situated around the same arteries. Mesocolic lymph nodes – Nodes for colon and they are mostly situated in the mesocolon. Drain into the celiac lymph nodes. Inferior mesenteric lymph nodes – Nodes along the inferior mesenteric artery, draining the descending colon, sigmoid and part of the rectum. Drain into the pre-aortic lymph nodes. Trunks Intestinal trunks – Drain the regions that are supplied by the superior and inferior mesenteric arteries. It empties into the cisterna chyli. Cisterna chyli – dilation of the thoracic duct, receive the lumbar and intestinal trunks. Drain into the thoracic duct. 30. The anatomy, blood supply and innervation of the kidney and the urether. The microcirculation of the kidney. Anatomy The kidney is retroperitoneal and extends from L1-L2 in erect position. The right kidney is a little lower. It is invested in a fibrous renal capsule and is surrounded by renal fascia. This fascia divides the fat into perirenal (perinephric space) and pararenal (paranephric space). At the hilus the urether renal vessels, urether and nerves exit and enter. In the order of VAU. It consists of medulla and cortex made up of approximately 1-2 million nephrons (see topic 31). Its arterial segments are the superior, anterosuperior, inferior and posterior segments. The kidney filters blood to produce urine, reabsorbed nutrients, ions and water. It also produce vasoactive substances and rennin (JG cells) The cortex is formed by the outer part of kidney into renal columns. It contains renal corpuscles, proximal and distal convoluted tubules. The medulla is formed by 8-12 pyramids which contain straight tubules, collecting tubules. At the apex of the pyramids the renal papilla is and it drains into the minor calyx which empty into the major calyx. Renal sinus is a space within the kidney, calyces, renal pelvis, vessels and verves held within various amounts of fat. Arteries: Right renal artery is longer. The renal arteries divide into 5 segmental arteries. Veins. Right and left renal veins, lie anterior to the renal arteries. The left is longer and receives the left suprarenal, the left gonadal and the ascending lumbar vein. They drain into the IVC. Innervation: Renal nervous plexus supplied by parasympathics and sympathetics from the abdominopelvic splanchnic nerves. Urether Muscular tube beginning in the renal pelvis extending to the urinary bladder. It is retroperitoneal. Have 3 constrictions: junction of urether and renal pelvis, crossing the brim of pelvic inlet, passage through the wall of the urinary bladder. Descends on the transverse processes of the lumbar vertebrae and the psoas muscle. Crossed anteriorly by the gonadal vessels (testicular a. and v.), crosses the bifurcation of the common iliac artery at the pelvis brim, run medial to the umbilical a. and the obturator vessels and finally crossed anteriorly again by the superior vesical artery before entering the urinary bladder. Blood supply: aorta, renal, gonadal, common and internal iliac, umbilical, superior and inferior vesical, and middle rectal a.a. Innervation: Lumbar (sympathetic) and pelvic (parasympathetic) splanchnic nerves Lymph drainage: Into common, external and internal iliac nodes. Microcirculation Blood circulation: renal a. → interlobar A.A. (between renal papillae) → arcuate a.a. (run in the border between the cortex and medulla) → interlobular a.a. thin branching of the arcuate) → afferent a.a (supply corpuscle) → capillaries (glomerular tuft) → efferent a.a. → peritubular capillary network (blood supply of the cortex) → vasa recta (only from those that are close to the juxtaglomerular apparatus.)→ stellate veins → interlobar v.v.→ arcuate v.v → Renal v. Mesangial cells: found in the glomerular capillaries. Are receptors for angiotensin II and naturetic factors. Release vasodilating substances. Synthesis of ECF, cytokines and prostaglandins. 31. The histology of the kidney and the urether. Electron microscopic structure of the nephron. Electron microscopic structure Histology Kidney - Have a medulla and a cortex with 1-2 million nephrons. A nephron consists of a renal corpuscle, proximal and distal convoluted tubules, thin and thick limbs of the Henle’s loop, and collecting tubules and ducts. Renal corpuscle: 200 µm in diameter has a glomerulus (tuft of capillaries) and a glomerular capsule (Bowman’s), which is divided into a visceral layer that envelopes capillaries, has primary and secondary podocytes, and pedicles, which filtrates and interdigitates slits. A parietal layer which acts as the outer limit of the corpuscle, simple squamous ept. basal lamina and reticular fibres. Between these two layers we find the urinary space which has a vascular (afferent arteriole enter and efferent arteriole exit) and a urinary pole (proximal con voluted tube begins). The basement membrane is the site of filtration, lamina densa acting as the physical filter and the lamina rara as the charge filter. Proximal convoluted tubule: cuboidal or low columnar ept. Wide lumen. Absorb glucose, amino acids and NaCl. Henle’s loops: Ascending and descending thick and thin segments. Simple squamous ept. Different length depending on where they are situated. Distal convoluted tubule: No brush border, cuboidal or low columnar ept. Maintenance of acid base properties of blood, sensitive to ionic content, aldosterone. Signals for renin. Collecting ducts: cuboidal to columnar cells. Collect into medullary rays. Juxtaglomerular apparatus: modifies smooth muscle, adjacent to corpuscle. Secretions play role in maintaining blood pressure. Laci’s cells (not understood). Secrete renin. Urether - Undistended it has an irregular lumen lined by mucosa, transitional ept. And a wide lamina propria (fibroelastic CT). Varying from polyhedral (intermediate cells) to cuboidal or low columnar (basal). The muscular layer: Upper portion consists of an inner longitudinal and an outer circular smooth muscle layer. And in lower third we can find an additional outer longitudinal layer. Adventitia: blends with the outer fibroelastic CT and adipose tissue, contains vessels and small nerves. 32. The development and malformations of the kidney. Development Develop from a common mesodermal ridge, the intermediate mesoderm. The kidneys are developed as 3 overlapping systems. Pronephros is the first system containing about 7-10 cells in the vertical region. Form nephrotomes that will regress before 4th week is over. Mesonephros it the second system and also include the formation of the mesonephric duct, both from the intermediate mesoderm. A – shaped loop will first form which aquire a glomerulus of arteries. Around this the Bowman’s capsule will form. The tubule itself will enter the Wolffian duct. The gonads will be formed on its medial side and together they will be known as the urogenital ridge. Metanephros is the final system which will appear in the 5th week. It develops from the metanephric mesoderm. Collecting ducts form from the ureteric bud, it will dilate to form the renal pelvis. This will penetrate metanephric tissue and form the calyces, and from these the collecting tubules. The metanephric tissue cap will form the renal vesicles giving rise to tubules. Capillaries growing into the tissue will form the glomerulus. The tubules will bind to the glomerulus and form the system of the kidney. The kidneys are initially formed in the pelvic region and latter shifts to a more cranial position. This is caused by the lengthening of body and the growth of the lumbar and pelvic regions. The arteries will also change and higher arteries from the aorta will attach. Malformations Wilms’ tumour – mutation of WT1 gene and can be associated with WAGR syndrome and Denys-Drash syndrome. Which are characterised by aniridia (absence of iris), hemihypertrophy respective pseudohermaphrodism. Renal dysplasias and agenesis - malformation severe enough for the patient to need dialysis. Multicystic dysplastic kidney – Nephrons fail to develop and the uteric bud fails to branch. Congenital polycystic kidney disease – numerous cysts form, may be inherited. Autosomal recessive polycystic disease – progressive disorder in which cysts form from the collecting ducts, large kidney with early renal failure. Autosomal dominant polycystic kidney disease – cysts form from all parts of the nephron and cause renal failure in adulthood. 33. The anatomy, blood supply, histology and development of the urinary bladder. Anatomy Situated below the peritoneum. Separated from the bones by the retropubic space. Lower in females. Extends above the pelvic brim when filled. Has an apex, fundus and base. Neck at the area where fundus and inferolateral surfaces come together. The bladder is held at this point by the lateral ligaments of bladder and the tendinous arch of the pelvic fascia. The uvula is a small eminence at the apex of the trigone and is projecting into the urethra. The trigone is bound by the two orifices of the urethers and the internal urethral orifice also called the internal sphincter. Smooth muscle fibres are called the detrusor muscle. Arteries: Superior and inferior vesical arteries. Veins: The prostatic or vesical plexus. Innervation: prostatic or vesical plexus, parasympathetic cause constriction and relaxation of internal sphincter and the sympathetic works the opposite. Lymph drainage: into the sacral, common iliac, internal or external iliac nodes. Histology Smooth muscle bundles in the urinary bladder are thicker than those in the urether. Layers of the urinary bladder are: mucosa, muscularis and serosa. Except for the inferior surface which has adventitia. Empty bladder: mucosal folds (not in distended), covered with a transitional ept. That is low columnar or cuboidal and a lamina propria (more elastic fibres in the deeper regions). Binucleate cells can also be found. 5-6 layers of cells. Plaques allow the empty bladder to fold, works like hinges. There are three muscular layers with interstitial CT in between them, here we find vessels. The interstitial CT merges with the serosa, which is the peritoneal mesothelium. Development The cloacae divides into the urogenital sinus anteriorly and the anal canal posteriorly, between these the urorectal septum is situated. Tip of this will form the perineal body. Upper and largest part of the urinogenital sinus is the urinary bladder and it is in the beginning continuous with the allantois. The urachus will replace this structure and form the connection with the umbilicus. The mesonephric duct will be absorbed into the wall of the urinary bladder. The trigone will be mesodermal since structures being incorporated are, but it will be replaced by endoderm with time. 34. The anatomy and histology of the female and male urethra. Anatomy Male - Muscular tube, 18-22 cm long. Conveys urine from the internal urethral orifice to the external urethral orifice. Through this tube semen also exits. Has a double curvature in non-erect state. Has 4 parts: preprostatic (intramural), prostatic, intermediate and spongy parts. The intramural part has a varying diameter and length depending on whether the bladder is filled or not. On the prostatic part there is a urethral crest which is located between the prostatic sinuses. On the prostatic sinuses the prostatic duct opens. The seminal vesicle opens onto the prostatic utricle on the urethral crest. Arteries: prostatic branches of the inferior vesical and middle rectal arteries. Veins: Prostatic venous plexus. Lymph drainage: mainly into the internal iliac nodes, but also into the external iliac nodes. Innervation: prostatic plexus arising from the inferior hypogastric nerve. Female – Pass from the internal urethral orifice posterior and inferior to the pubic symphysis and to the external urethral orifice anterior to the vaginal orifice. The urether is anterior to the vagina. Pass throught the pelvic diaphragm, external urethral sphincter and the perineal membrane. The superior part has urethral glands. The female urethra has more elastic fibres and is distensible. Arteries: internal pudendal and vaginal arteries. Veins: internal pudendal and vaginal veins. Lymphatics: sacral and internal iliac nodes, but also the inguinal lymph nodes. Innervation: vesical nerve plexus and the pudendal nerve. Histology Male - Penile urethra is enclosed by the corpus spongiosus. It is lined by pseudostratified or stratified columnar ept. surrounded by a thin lamina propria. Urethral lacunae are found in the lumen, these contain mucous cells. But they are also connected to the urethral glands of Littre, which can be found in the surrounding CT. Ducts from these also opens into the lumen. On the prostatic part a blind tube, the verumontatum can be found. Prostatic part is lined by transitional epithelium. The external sphincter is made by smooth muscle. In the spongious part there are pseudostratified columnar ept. But areas of stratified and squamous can be found. Female – Has stratified squamous and pseudostratified columnar epithelium. The midpart is surrounded by a voluntary external striated sphincter. 35. The development and the malformations of the ovary, uterine tube, uterus and vagina. Development The gonads are developed from the genital or gonadal ridges and germ cells invade these from the endoderm of the yolk sack. Before the germ cells are incorporated, the ridges become primitive sex cords. Ovary – Surface epithelium of the gonads proliferates and generates cortical cords which penetrate the underlying mesenchyme. They will split in the 4th month into isolated clusters surrounding one or a few primitive germ cells. The epithelium will form the follicular cells and the walls of the ovaries. Uterus and uterine tube – The paramesonephric duct arises from the longitudinal invagination of the anterolateral epithelium of the urogenital ridge. Cranially it opens into the abdominal cavity; caudally it runs laterally to the mesonephric duct. These two ducts will fuse and form the uterine canal. The caudal tip of the uterine canal swell and the mesonephric duct opens into the urogenital sinus. The part fusing with the abdomen and the horizontal part crossing the mesonephric duct will form upon the descent of the ovaries the uterine tubes. The other part becomes the uterus. The broad ligament of the uterus is formed by the fusion of the two ducts. Body and cervix arise from the mesonephric duct. Vagina – evaginations grow out from the pelvic part of the urogenital sinus and forma vaginal plate. It continues to grow in cranial position towards the uterine canal and at the 5 th month it is fully out grown. The vaginal fornices are of paramesonephric origin. A thin plate of tissue, the hymen remains between the vagina and the urogenital sinus. Malformations Uterus didelphysis – it the duplicature of uterus as a result of the lack of fusion of the paramesonephric duct. Each uterus has one vagina. Uterus arcuata it a less severe form with just an indentation in the middle. Uterus bicornis – the uterus has two horns entering one vagina. Atresia of cervix – in cases of the lack of fusion of one or both of the paramesonephric ducts. This type involves both sides. 36. The anatomy, histology and development of the female external genital organs. Anatomy Labia majora - two longitudinal folds of skin from mons pubis to the anterior labial commeasure. Terminations of the round ligament. Labia minora - Hairless and with no fat. Upper part form prepuce and lower part the fraenulum. Vestibule of the vagina: cleft between the labia majora. Openings for the uterus, vagina and vestibular glands on its floor. Clitoris - consists of erectile tissue, divided into two crura, two corpora and a glans. Glans is covered by sensitive epithelium. Bulbs of the vestibule - paired mass of erectile tissue on each side of the vaginal orifice. Covered by the bublbospongiosus muscle. Histology Clitoris - covered by stratified squamous ept. And has two erectile bodies. Labia majora - folds of skin with adipose tissue and curly hair. Labia minora - folds of skin, spongy CT, sebaceous and sweat glands. Development The mesenchymal cells around the cloacae form cloacal folds. They fuse with the cranial membrane to form the genital tubercle. They divide into urethral and anal folds. On the side of the urethral folds the genital swellings becomes visible. The genital tubercle elongates and forms the clitoris, the urethral folds form the labia minora and the genital swellings becomes the labia majora. The vestibule is formed by the urogenital groove. 37. The anatomy, blood supply and innervation of the penis. Development of the male external genital organs. Anatomy Have corpora cavernosa (paired on the side) and a corpus spongiosum (midline) which are vascular erectile tissue bound by the tunica albuginea. This also constitutes the body. The root is made from the two crura and the bulb of penis. Head is the glans penis (terminal part of corpus spongiosum) covered by the prepuce, which is a fold of skin. Underneath this we find the fraenulum. Margin of glans penis is the corona, and the slit at the top is the external urethral orifice on which the urethra dilates into the fossa navicularis. Layers: skin, superficial fascia (with deep dorsal veins), Deep (Buck’s) fascia, tunica albuginea enclosing the corpus cavernosum (has the deep artery) and forming a septum in between them. Corpus spongiosum encloses the urethra. Below the superficial fascia the deep dorsal vein, dorsal a. and dorsal nerve can be found. Suspensory ligament goes from the pubic symphysis to the deep fascia. Fundiform ligament is an irregular mass that goes from the linea albea to the pubic symphysis. Arteries: Branches of the internal pudendal arteries. → dorsal a.a., deep a.a. Superficial and deep branches of the external pudendal artery supplies the skin. Veins: Drained by a venous plexus that joins the deep dorsal vein of penis. Superficial dorsal vein drains into the superficial external pudendal vein. Lymph drainage: lymph from skin goes into the superficial inguinal nodes and the deep parts into the deep inguinal and external iliac nodes. Innervation: S2-S4, sensory and sympathetic from the dorsal nerve of penis, a branch of the pudendal n. Ilioinguinal nerve branches supplies the root. Mechanisms of erection Parasympathetic stimulation from the pelvic splanchnic nerves dilates the arteries supplying the erectile tissue. Causing this tissue to fill up with blood and compress the veins, impeding venous return. Contraction of the bulbospongiosus and ischiocavernosus muscle also compresses erectile tissue, helping to maintain erection. “Point and shoot.” Histology Consists of 3 cylindrical masses, the corpora cavernosa (2 of the bodies) and the corpus spongiosum (ventrally). The latter dilates at the end and forms the glans penis. The urethra is lined by pseudostratified columnar epithelium and in the glans penis it becomes stratified squamous epithelium. Throughout the length of the urethra in the penis the glands of Littre can be found. The prepuce is a retractile fold of skin, CT with smooth muscle. The copora cavernosa is covered by dense CT, the tunica albuginea. The corpora cavernosa and spongiosum is made of erectile tissue, numerous venous spaces separated by trabeculae of CT and smooth muscle. Development The mesenchymal cells around the cloacae form cloacal folds. They fuse with the cranial membrane to form the genital tubercle. They divide into urethral and anal folds. On the side of the urethral folds the genital swellings becomes visible. Under influence of androgens. The genital tubercle rapidly elongates and is now called the phallus. The phallus pulls the urethral folds forward and they form the lateral walls of the urethral groove. The epithelium of this groove forms the urethral plate. They will close and form the penile urethra. Ectodermal cells of the tip will form the last bit of the urethra. It also forms the external urethral meatus. The scrotal swellings move caudally. 38. The anatomy and histology of the vas deferens, the prostate and seminal vesicle. Anatomy Seminal vesicle - Lobulated glandular structures that are enveloped by endopelvic fascia, Superior end are covered by peritoneum and the urethers. Together with the ductus deferens they form the ejaculatory duct. Can be found inferior and lateral to the ampulla of the ductus deferens against the fundus of the bladder. Function: Produce fructose and choline, alkaline. Blood supply: inferior vesical and middle rectal a.a. Drained by veins of similar names. Lymphatic drainage: external and internal iliac nodes. Ejaculatory ducts: union of ductus deferens and the seminal vesicle, contraction of this and the ductus deferens propels sperm forward into the urethra. Open into the prostatic urethra on the seminal colliculus just lateral to the blind prostatic utricle. Arteries: artery to the ductus deferens. Veins: Drained by the prostatic and the vesical venous plexuses. Lymph drainage: external iliac nodes. Prostate - At the base of the bladder and consists of glandular tissue with smooth and fibrous tissue. Surrounded by a visceral layer of the pelvic fascia. Ducts open into the prostatic sinus on the side of the urethral crest. Receives the ejaculatory duct on the seminal colliculus lateral to the prostatic utricle. Lobes: anterior, middle (hypertrophy), posterior (carcinomatous transformation), left and right Function: secretes fluids responsible for the odour, which is a part of semen. Also secretes prostaticspecific antigens, prostaglandins, citric acid, acid phosphatases and proteolytic enzymes. Arteries: inferior vesical, internal pudendal and middle rectal a.a. ← internal iliac a. Veins: Drained by the prostatic venous plexus. Lymphatic drainage: mainly to the internal iliac nodes but sometimes also to the sacral nodes. Vas deferens – Thick walled tube entering the pelvis at the deep inguinal ring. Cross the medial side of the umbilical artery and obturator nerve and vessels. Dilates and becomes an ampulla at the end. Contains fructose and receives innervation mainly from the hypogastric and pelvic plexuses. Histology Seminal vesicle - Is a tortuous tube, about 15 cm long. Has a folded mucosa into primary or secondary folds, form mucosal crypts. Have cuboidal or pseudostratified columnar ept. And secretory granules. In the lamina propria we find elastic fibres and smooth muscle. Muscular layer consists of an inner circular layer and an outer longitudinal layer. Adventitia. Prostate - Consists of 30-50 branched tubuloacinar glands that empty into the prostatic urethra. Some of these glands form solid secretory aggregations, called concretions. Have cuboidal or pseudostratified columnar epithelium. The fibroelastic capsule around the prostate divides it into lobes, this also contains smooth muscle. Structure and function depends on the level of testosterone. Vas deferens – Irregular lumen with longitudinal mucosal folds. It has a thick muscularis and adventitia. The lumen is lined by pseudostratified columnar epithelium. Inner longitudinal, middle circular and outer longitudinal muscular layers. The adventitia is rich in blood vessels. 39. The development and malformations of the male genital system Development The gonads are developed from the genital or gonadal ridges and germ cells invade these from the endoderm of the yolk sack. Before the germ cells are incorporated, the ridges become primitive sex cords. The primitive sex cords continue to proliferate and penetrate deep into the medulla to form the testis or the medullary cords. These cords will form the rete testis. Dense CT, tunica albuginea, separates the testis from the surface epithelium. In the 4t month it is shaped like a horse shoe and consists of primitive germ cells and Sertoli’s cells. Leydig's cells are derived from the mesenchyme of the gonadal ridge and begin to produce testosterone in the 8th week. In puberty the seminiferous tubules are formed and they join the rete testis, forming ductus efferents. The genital ducts are formed by the mesonephros regress, the epigenital tubules. They join the rete testis and become the efferent ductules. The mesonephric ductules form the main genital ducts. Between the epididymis and the seminal vesicle the mesonephric duct form the ductus deferens, and beyond this point the ejaculatory duct. During the second month urogenital mesentery attaches to the testis. When the testis descends the gubernaculums grows and extends from its inguinal region towards the scrotal floor. Malformations 40. The histology of blood: morphology of formed elements, cell size and number. Erythrocytes Anucleated packed with haemoglobin. Biconcave disk with the measures 7,5μm in diameter, 2,6μm thick at the rim ad 0,8μm at the centre. It is flexible and can change shape if needed when entering the smaller capillaries. Its membrane consists mostly of lipids and proteins. There are 3,9-5,5 million per microliter in women and 4,1-6 million per microliter in men. Leukocytes White blood cells. Neutrophil – account for 60-70% of the circulating leukocytes which is about 5000 per microliter. They are 12-15 micrometer in diameter, and a nucleus with 2-5 lobes linked by chromatin. It contains two types of granules, specific and azurophilic (lysosomes). Neutrophils can survive in anaerobic conditions. They have a half life of 6-7 h in blood but 1-4 days in connective tissue. They are active phagocytes. Eosinophils – only 150 can be found per microliter and this represents 2-4% of the total number. They have about the same size as neutrophils but have a bilobed nucleus. Major basic protein makes the eosinophil. Have large elongated refractile specific granules. Basophils – There are about 30 per microliter which is less than 0,5% of the total. They are 12-15 micrometer in diameter and have an irregular lobed nucleus. It has specific granules with heparin and histamine. They are more irregular than other WBC. They are precursors to mast cells. Lymphocytes – Spherical cells can be from 6-18 micrometer in diameter. They have a spherical nucleus with a small indentation. There is very little cytoplasm. They have a varied life span, from a few days to couple of years. About 2400 per microliter. Monocytes – Bone marrow derived with diameters in between 12-20- Oval or horseshoe shaped nucleus. Monocytes stain lighter than lymphocytes. Monocytes will differentiate into macrophages in CT. Around 350 per microliter. Platelets Small nonnucleated disk-like cells. Have a diameter of 2-4 micrometer. Derive from the megakaryocyte that is found in the bone marrow. They vary from 200 000 – 400 000 in blood. They have an open canalicular system which facilitates the release of active molecules stored in them. In the periphery there is a marginal bundle that keeps them in oval shape. There are beta and alfa bodies. The beta bodies contain calcium, phosphate, adenosine diphosephate, and adenosine triphosphate and serotonin. The alfa bodies contain fibrinogen, platelet-derives growth factor. They control haemorrhage. 41. The histology of red bone marrow. Erythropoiesis. Bone marrow Bone marrow produces blood cells and is found in the medullary canals of the longbones and in cavities of cancellous bones. It is divided into red and yellow bone marrow. Yellow produces mainly adipose cells. Red bone marrow – It is composed of stroma, haematopoietic cords and sinusoidal capillaries. The stroma contains of collagen type I and II, fibronectin, laminin and proteoglycans. The cells of the stroma are bound by these materials. The sinusoids are a discontinuous layer of endothelial cells. These are reinforced by reticular cells and a net of reticular fibres. The release of bone marrow cells are controlled by many releasing factors. Erythropoiesis The maturation of erythrocytes involves the synthesis of haemoglobin and the formation of the corpuscle. There are several factors and hormones responsible for this process, such as iron, folic acid, cyanocobalamin and erythropoietin. The differentiation starts with the formation of the proerythroblast (large and have a well visible nucleoli). Next the basophilic erythroblast is formed, it stains strongly basophilic and has a condensed nucleus with no visible nucleoli. Basophilia is due to polyribosomes in the cytoplasm, they will decrease in number for the next stage. The areas once occupied by the polyribosomes now begin to fill with haemoglobin causing the cell to be stained in several colours. Polychromatic erythroblast. The nucleus will condense further and the basophilia will disappear forming the orthochromatic erythroblast. Finally the nucleus will be expelled through a series of cytoplasmic protrusions, it will be phagocytosed by macrophages. The remaining reticulocyte will still have polyribosomes, but will loose them before becoming the mature erythrocyte 42. Granulopoiesis and thrombopoiesis. The origin and differentiation of the lymphocytes. Granulopoiesis The maturation involves the synthesis and storage of proteins in the cytoplasm, they are packed into azurophilic and specific granules. The azurophilic will be produced in the first staged, followed by the production of the specific. It starts with the myeloblast which has visible nucleoli. The promyeloblast follows and it has the visible granules. This one will give rise to 3 different types of myelocytes, neutrophilic, basophilic and eosinophilic. The nucleus in these will have further condensed to form give more space for the granules. Neutrophil differentiation – this takes about 11 days and it will pass through four different compartments, the medullary formation, medullary storage, circulating and marginating compartment. The neutrophil pass through the early neutrophilic myelocyte stage, late neutrophilic myelocyte stage, neutrophilic metamyelocyte stage, band cell and finally become the mature neutrophil. Eosinophilic differentiation – from the promyeloblast into the early eosinophilic myelocytes, late eosinophilic myelocyte, eosinophilic metamyelocyte and finally mature eosinophil. Basophil differention – Early basophilic myelocyte, late basophilic myelocyte and then mature basophil. Thrombopoiesis Platelets originates from the fragmentation of the cytoplasm of mature megakaryocytes (derive from megakaryoblasts). Megakaryocytes are giant cells with an irregular lobulated nucleus and lots of mitochondria in the cytoplasm. Platelets have conspicuous granules originating from the golgi complex. They contain factors such as platelet-derived growth factor, von Willebrand’s factor and fibroblast growth factor. The plasma membrane will invaginate and form demarcation membranes. This defines the areas of the megakaryocyte cytoplasm that will shed the platelets into circulation. Lymphocytes Originates in the thymus and the peripheral lymphoid organs but the progenitor cells come from the bone marrow. Some mature in bone marrow and become B lymphocytes others migrate to the thymus and mature into T lymphocytes. The B lymphocytes migrate to peripheral lymphoid organs where they multiply. The first progenitor is the lymphoblast which can incorporate [ 3H]thymidine. Then divide 2-3 times and form prolymphocytes. The plasma membrane cell-surface antigens mark these cells as B or T lymphocytes. Monocytes Monoblast is almost identical to the myeloblast and its differentiation leads to promonocyte. The promonocyte will divide once or twice to form the monocyte. They hold a lot of azurophilic granules originating from the endoplasmic reticulum and golgi apparatus. 43. The anatomy of the lymphatic system: major lymphatic vessels and trunks in the body. Anatomy Drains one-way towards the heart through the thoracic duct into the left lymphatic duct. From the lower limbs the lymph is drained into the superficial and deep lymph vessels passing a number of nodes such as popliteal, superficial and deep inguinal, inguinal and lumbar before entering the cisterna chyli. The cisterna chyli is a lower dilation of the thoracic duct and the thoracic duct drains into the right lymphatic duct. The left arm (and the right) contains superficial and deep lymphatic vessels as well, these drain into the axillary lymph nodes and then into the angle between the left subclavian and the internal jugular vein. The head is drained through the jugular trunk. The upper right quadrant does not drain into the thoracic duct but into the right subclavian, right bronchomediastinal and right jugular trunk. Then into the right angle between the right subclavian and internal jugular. The thoracic duct is usually beaded because of its many valves. It drains the lower limb, abdomen, left thorax, left upper limb and left side of the head and neck. It passes through the aortic opening of diaphragm and descends between the aorta and the azygous vein in the posterior mediastinum. Arches over the left pleura and into the left carotid sheath, goes behind the left internal jugular and empties into the junction of the left internal jugular and subclavian. 44. The histology of the lymph node. Histology Lymph nodes are elongated kidney shaped organs. The convex surface serves as the entry of lymphatic vessels and the hilum (concave) surface is where arteries and nerves enter the lymph node, and veins and lymph vessels exit it. The entire lymph node is surrounded by a CT sheath. The most common cells of the lymph node are the lymphocytes, macrophages, APC’s, plasma cells and reticular cells. The lymph node is divided into a cortex and a medulla. The cortex consists of a diffuse population of T-lymphocytes and reticular cells (macrophages and APC’s). B lymphocytes form nodules in this part of the tissue. There are also subcapsular sinuses which is a loose network of reticular cells and fibres. Lymph circulates in these and channels from the afferent lymphatic vessels. Radial sinuses run between the nodules. The medulla consists of medullary cords that arise from the inner cortex and contain primarily B lymphocytes. They are cordlike extensions. The spaces in between these cords are the medullary sinuses that contain lymph, lymphocytes and macrophages. Deliver lymph to the efferent lymph vessels. Afferent vessels pour into the subcapsular sinus, then through the radial sinuses into the medullary cords and spaces to be delivered to the efferent vessels. 45. The anatomy, histology and development of the thymus. Anatomy It is a primary lymphoid organ on the inferior part of the neck and the anterior part of the superior mediastinum. It is lobulated into right and left lobe, but these are further lobulated by CT. During and after puberty it will gradually become replaced by fat tissue. Arteries: anterior intercostal and anterior mediastinal of the internal thoracic arteries. Veins: veins of thymus end in the left brachiocephalic, internal thoracic and inferior thyroid veins. Lymphatic vessels: end in the parasternal, brachiocephalic and tracheobronchial nodes. Histology It has a CT capsule that penetrates the parenchyma and divides it into lobules. It has a cortex and a medulla. The cortex is populated by T cell precursors, epithelial reticular cells and macrophages. The epithelial reticular cells are joined to other cells by desmosomes. There are also thymic nurse cells which contain 20-100 maturing lymphocytes in their cytoplasm. The medulla contains epithelial reticular cells, differentiated T lymphocytes and Hasall's corpuscles. The latter are flattened epithelial reticular cells filled with keratin and are concentrically arranged. The capillaries in the thymus have thick non fenestrated epithelium and they are quite impermeable. They form the thymic-blood-barrier. In the cortex they gain the CD4+ and CD8+ character. Development The thymus is derived from the third pharyngeal pouch. The dorsal wing differentiates into the inferior parathyroid gland and the ventral wing into thymus. These structures will loose their connection to the pharyngeal wall and migrate caudally. Growth of thymus will continue until puberty when it will start to be replaced by fatty tissue. It has dual embryonic origin, its lymphocytes come from bone marrow (mesenchyme) and the endoderm of the third pharyngeal pouch. 46. The spleen: the anatomy, histology, blood supply and development. Anatomy It is a large vascular lymphatic organ against the diaphragm at rib 9-10. The spleen has the size and the shape of ones fist. The diaphragmatic surface is curved, the anterior and superior borders are sharp and notched and the posterior and inferior is rounded. It is supported by the lienorenal and lienogastric ligaments. Arteries: splenic artery Vein: splenic vein Lymphatics: lymph nodes in the splenic hilum to the pancreaticosplenic lymph nodes. Innervation: celiac nerve plexus. Histology The spleen is invested into a dense CT capsule, this sends trabeculae into the spleen dividing the splenic pulp. The trabeculae also carried nerves, veins and arteries. White pulp – splenic artery divides into trabecular arteries and when entering the pulp they become invested in a sheath of T lymphocytes (PALS). They will receive lymphoid nodules of B lymphocytes and the artery will turn into an arteriole. It will also give of a number of radial arteries during its course. The lymphoid nodule is surrounded by many radial arteries. The sheath will diminish and the arterioles become penicillar arterioles when they leave the white pulp. Red pulp - Consists of splenic cords and sinusoids. They contain T and B lymphocytes, macrophages, plasma cells and many blood cells. These structures are lined by endothelial cells but the sinusoids are also lined by an incomplete basal lamina. Development The spleen develops as a primordium between the two leaves of the dorsal mesogastrium. With the rotation of stomach the spleen swings left of the midline and fuses with the peritoneum of the posterior abdominal wall. The spleen remains intraperitoneal and is connected with its two ligaments. 47. The pituitary gland: anatomy, histology, blood supply and development Anatomy It weighs 0,5 g and is about 10 X 13 X 6 mm. It lies in the cavity of the sphenoid bone (sella turcica). It consists of two glands, the neurohypophysis and the adenohypophysis. Blood supply: internal carotid artery gives of two branches the superior and inferior hypophyseal arteries. The superior becomes a plexus irrigating the stalk and median eminence, then become a secondary plexus in the adenohypophysis. It carries hormones from the neurohypophysis to the adenohypophysis. Histology Adenohypophysis Pars distalis - are cords of epithelial cells within the capillaries. Accounts for almost 75% of the total mass. The hormones produced here are stored in secretory granules. Consists of 3 types of cells, chromophobes, basophils and acidophils. The subtypes are named after the hormone they produce. The hormones secreted by these cells control all other endocrine glands. The hormones regulating pars distalis are the hypothalamic releasing hormone and hypothalamic inhibiting hormone. They are brought to the pars distalis via the capillary plexus from hypothalamus and neurohypophysis. Certain tissue hormones control the nerve impulses to hypothalamus or other structures and therefore control the pars distalis. Pars tuberalis – funnel shaped region around the infundibulum of neurohypophysis. Secrete gonadothropins and are arranged along the blood vessels. Pars intermedia – develops from the dorsal portion of Rathke’s pouch and are a region made up of corda and follicles, secrete alfa-melanocyte stimulating hormone. Neurohypophysis Pars nervorsa – it is composed of some 100 000 unmyelinated axons of secretory neurons, but also some pituicytes. These come from the supraoptic or paraventricular nuclei. They have well developed Nissl bodies that carry neurosecretory material. This material is stored in the nerve endings as Herring's bodies. The Herrings bodies are large 100-200 nm and release their content into fenestrated capillaries. The neurosecretory materials are two hormones, vasopressin and oxytocin. They are released as a response to impulses in the nerve fibres. Development It develops from the ectoderm of the stomodeum in front of the buccopharyngeal membrane (Rathke’s pouch) and an extension of the diencephalon, the infundibulum. The Rathke’s pouch begins to grow in the 3rd week towards the infundibulum. At the second month it looses its connection with the oral cavity. It forms the adenohypophysis. Pars tuberalis grows along the neural stalk. 48. The thyroid and parathyroid glands: anatomy, histology, blood supply and development. Anatomy Thyroid – It consists of a right lobe and a left lobe connected by an isthmus. It crosses the 2nd-3rd tracheal rings. Arteries: superior and inferior thyroid arteries (thyroid ima artery sometimes as well) Veins: superior, middle thyroid veins into the internal jugular vein and to the inferior thyroid vein to the brachiocephalic vein. Parathyroid gland – are endocrine glands vital to the regulation of calcium and phosphorus metabolism. It is 4 small ovoid bodies on the dorsum of the thyroid. They have their own capsule but lie under the thyroid sheath. Arteries: inferior thyroid artery. Histology Thyroid – it synthesises the hormone thyroxine and triiodothyronine. The thyroid consists of millions of thyroid follicles, they are lines by simple epithelium and contain a colloid. The secretory product is stored in large amounts. The colloid is composed of thyroglobulin. The gland is covered by a CT capsule and it sends septa into it. The endothelium of the capillaries in this gland is fenestrated. In the thyroid another type of cell can also be found, the parafollicular cell. It is found in clusters in between the follicles. They are responsible for the production and secretion of calcitonin. It is triggered by the elevation of calcium levels in the blood.. The thyroid is stimulated by TSH secreted from the anterior pituitary gland. Parathyroid – The capsule they are invested in sends septa into them and they support elongated cords of secretory cells. The cells found in the parathyroids are chief cells and oxyphil cells. The chief cells contain the parathyroid hormone. It binds to osteoblasts which secrete osteoclast-stimulating factors. Development Pharyngeal gland – the third pharyngeal pouch differentiate the epithelium of the dorsal wing to the inferior parathyroid gland. The superior parathyroid gland is differentiated from the fourth pharyngeal pouch. 49. The adrenal gland: anatomy, histology, blood supply and development. Anatomy It is retroperitoneal on the superomedial aspect of kidney. The glands are surrounded by the renal fascia and a capsule. The right one is pyramidal and the left one is semilunar. The suprarenal arteries branch freely and 50-60 arteries penetrate the surrounding capsule. Arteries: superior supra renal artery from inferior phrenic artery, middle suprarenal from the abdominal aorta and the inferior supra renal from the renal artery. Veins: right suprarenal vein into the IVC and left suprarenal vein into the renal vein. Lymphatics: lymph into the plexus below it and then into the lumbar lymph nodes. Innervation: Comes from the celiac and abdominopelvic splanchnic nerves. Histology The adrenal gland is divided into a medulla and a cortex. The blood supply is through the many arteries penetrating the capsule and these are then further divided into 3 groups. Those that supply the capsule, the cortical arteries and medullary arteries. The adrenal cortex is divided into 3 layers. The first is the zona glomerulosa beneath the capsule. It has columnar or pyramidal cells and secretes mineralocorticoids such as aldosterone. The next layer is the zona fasciculate and it has cells in cordlike structure, the cells are polyhedral and secrete glucocorticoids such as cortisol. The final layer the zona reticularis are formed from irregular cords and the cells in this layer is smaller than all the others. They secrete androgens. ACTH is the hormone from the hypophysis that controls the cortex of the adrenal gland. The medulla contains polyhedral cells arranged in clumps or cords. They are supported by reticular fibres. The secretory granules of these cells contain epinephrine and norepinephrine. It mainly produces epinephrine. Development The cortex is of mesodermal origin and it comes from the root mesenchyme and gonads. The mesothelial cells of these structures proliferate and form the large acidophilic organs such as the fetal cortex. These are yet again penetrated the mesenchyme and the new mesenchyme cells surround the formed acidophilic cells. Neural crest cells will invade the medial aspect and form cords and clusters. These cells will form the medulla. 50. The anatomy and histology of the integumentary system. Anatomy The integumentary system consists of the skin and sweat glands, sebaceous glands, hair and nails. There are also several types of sensory nerve endings. Skin - serves as a protective layer and a sense organ. But it is also important in the regulation of temperature, production of vitamin D and absorption. Dermatomes – Each part of the skin has a sensory component of each of the spinal nerves. When the integumentary system was developed the nerve for each spinal segment innervating the viscera also came to innervate a certain part of the skin and muscle. This is the reason that the pain felt may not be an actual pain in the skin but rather a visceral pain. Histology Epidermis is the outermost stratified keratinized squamous epithelium. Within this epithelium one can find melanocytes, langerhans cells and Merkel’s cells. The epidermis consists of 5 layers from the dermis and out. First is the stratum basale which is a single layer cuboidal cell at the epidermal-dermal junction Desmosomes and hemidesmosomes binds these layers. It contains stem cells and has therefore intense mitotic activity. Second is the stratum spinosum which consists of cuboidal cells with keratin in. Bound together by filament-filled cytoplasmic spines and desmosomes. Visible keratin it the tonofilaments. All mitoses are confined to the malpighian layer which is the border between the two first layers. Langerhans cells can be found in this layer, they bind, process and present antigens to T lymphocytes. Stratum granulosa comes next, consists of 5 layers of flattened polygonal cells. These cells have keratohyalin granules. There is also a membrane-coated lamellar granule. These fuse with the cells and empty their contents into the cells. Acts as a barrier against foreign materials. Stratum lucidum is the fourth layer and it is a thin layer of flattened cells with desmosomes binding them together. Stratum corneum is the last layer and it consists of 15-20 layers of flattened nonnucleated keratinized cells. They are also called the horny cells. Melanocytes are the cells of the skin responsible for its colour. They contain melanin or carotene. These are derived from the neural crest cells. At the soles and the palms Merkel cells can be found, these are sensory mechanoreceptors. Dermis – CT that supports the epidermis. It is irregular and shows the structure of dermal papillae. The dermal layer closest to the papillae is the papillary layer and it consist of looser CT and mast cells, it is also rich in nerves and effectors. The subcutaneous tissue under the dermis (hypodermis) binds the skin to underlying organs and structures. There are a few types of nerve-endings in the skin, the expanded are the Ruffini endings, Vater-Pacini, Meissner and Krause endings are the encapsulated corpuscles. Hairs – Elongated keratinized structures invaginating into the papillae. Each hair comes from a hair follicle, the dilation part in the skin are the hair bulb closing the dermal papillae in. The hair is divided into a medulla and a cortex. Around the cortex there is another layer forming the cuticle of the hairs, which are tall columnar cells. Then before leaving the skin the hair is also surrounded by the internal root sheath, coated by the external root sheath. A hyaline layer separates the hair from the dermis, this is called the glassy membrane. The arrector pili muscles are bound to this layer. Nails – plates of keratinized epithelium on the dorsal surface of each distal phalanx. Hidden in the nail groove is the nail root. The stratum corneum forms the cuticle of the nail. The nail plate rests on an epidermal nail bed. Sebaceous glands – are found in the dermis and they are most frequent on the face, head and scalp. They are acinar glands and produce sebum. They are also holocrine glands since they secrete their remnants on dead cells. Sebum is a mixture of lipids, waxes, squalene and cholesterol. Sweat glands – These are merocrine glands that are simple coiled tubular. There are two types of cells in these, the dark cells which are pyramidal and have secretory granules with glycoprotein, and clara cells with no secretory granules. Sweat consists of water, sodium chloride, urea, ammonia and uric acid. Apocrine glands can be found in the axillary, areolar and anal regions. 51. The anatomy, histology and development of the mammary gland. Anatomy The breast is extends from the 2-6 rib, from sternum to mid axillary line. The mammary gland lies in the superficial fascia and the breast is supported by the suspensory ligaments (Cooper’s ligaments). It has a nipple and an areola. The mammary gland is a modified sweat gland. It has an axillary tail and a small part of it extends superolaterally through the deep fascia. It is separated from the deep tissue by the retromammary space, this permits movement of the breast. It has 15-20 lobes of glandular tissue, separated by fibrous septa radiating from the nipple. Each lobe opens into a lactiferous duct. The ducts open on the lactiferous sinus, a place for storage of milk during lactation. Arteries: medial mammary branches of the internal thoracic, lateral mammary from the lateral thoracis artery and pectoral branches of the posterior intercostal arteries. Innervation: anterior and lateral cutaneous branches of the second to sixth intercostal nerves. Histology The main characteristics of the gland is the lobe, a lobe is several ducts emptying into a terminal duct. Each lobe is embedded into loose CT. Near the nipple they dilate and form the lactiferous sinus. The lining of these ducts are of stratifies squamous epithelium at the sinuses and columnar to cuboidal further into the tissue. The tissue around the lobes is rich in lymphocytes and plasma cells. Cells proliferate at time of ovulation when estrogen levels are high. Alveoli will proliferate in pregnancy and at the terminal duct. These are active milk producing and secreting structures. The epithelial cells of the alveoli will produce milk during lactation. Development The mammary glands begin to develop as thickenings of the epidermis in the form of bands, also called the mammary line. Only a small portion of this band will remain in the thoracic region. It will penetrate the underlying mesenchyme. It gives rise to first sprouts and then small, solid buds. They will be canalised and form lactiferous ducts at the end of prenatal life. The nipple develops after birth from an epithelial pit onto which the glands first empty.