LEGACY UNIVERSITY, THE GAMBIA Knowledge and Research for Integrity ANA 212 LECTURE WEEK THREE BATCH ONE SUMMER SEMESTER. - презентация

1 LEGACY UNIVERSITY, THE GAMBIA Knowledge and Research for Integrity ANA 212 LECTURE WEEK THREE BATCH ONE SUMMER SEMESTER.

2 EMBRYOLOGY& HISTOLOGY OF THE ENDOCRINE ORGANS Embryological Development Of The Parathyroid Glands The superior parathyroids differentiate from the 4th branchial pouch. The inferior gland develops from the 3rd pouch in company with the thymus As the latter descends, the inferior parathyroid is dragged down with it. It is thus easily understood that the inferior parathyroid may be dragged beyond the thyroid into the mediastinum and why, although very rarely, parathyroid tissue is found actually within the thymus.

3 Legend depicting The Normal and abnormal sites of the parathyroid glands (lateral view).

4 Legend For The derivatives of the branchial pouches. Note that the inferior parathyroid migrates downwards from the 3rd pouch whereas the superior parathyroid (4 th pouch) remains stationary.

5 Applied Anatomy Of The Development Of The Parathyroid Gland. Clinical Applications. [1]- These possible aberrant sites are, of course, of great importance in searching for a parathyroid adenoma in hyperparathyroidism. [2]- The parathyroids are usually safe in subtotal thyroidectomy because the posterior rim of the thyroid is preserved. However, they may be inadvertently removed or damaged, with resultant tetany due to the lowered serum calcium.

6 The Pharyngeal System & Its Derivatives Six visceral arches form on the lateral aspects of the fetal head separated, on the outside, by ectodermal pharyngeal clefts and, on the inside, by five endodermal pharyngeal pouches.

7 Legend For The derivatives of the branchial pouches. Note that the inferior parathyroid migrates downwards from the 3rd pouch whereas the superior parathyroid (4 th pouch) remains stationary.

8 Embryology Of The Endocrine Glands In the human embryo the 5th and 6th arches do not appear externally and are represented only by a mesodermal core. Each arch has its own nerve supply, cartilage, muscle and artery, although considerable absorption and migration of these derivatives occur in development. The 5th arch disappears entirely. The embryological significance of many of the branchial derivatives has already been discussed under appropriate headings (the development of the face, tongue, thyroid, parathyroid and aortic arch) but this annotation serves conveniently to bring these various facts together.

9 TABLES FOR DERIVATIVES OF THE PHARYNGEAL SYSTEM (NOTE THAT THE 5TH ARCH DISAPPEARS EXCEPT ITS INTERNAL POUCH). SINCE,The parafollicular calcitonin-producing cells are now known to come from the ultimobranchial body (fifth pharyngeal pouch),

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14 Branchial Cyst &Branchial Fistula Branchial Cyst The second branchial arch grows downwards to cover the remaining arches, leaving temporarily a space lined with squamous epithelium. This usually disappears but may persist and distend with cholesterol containing fluid to form a branchial cyst. Another theory proposed is that these cysts arise from squamous clefts in cervical lymph nodes.

15 Branchial Cyst &Branchial Fistula Branchial Fistula If fusion fails to occur distally, a sinus persists at the anterior border of the origin of the sternocleidomastoid; this branchial fistula can be traced upward between the internal and external carotids and may even open into the tonsillar fossa, demonstrating its association with the second branchial arch.

16 Embryology&Histology Of The Adrenal Gland Embryology: The adrenal glands have two embryonic origins, and consequently produce two different types of signalling chemicals. The outer cortex is of mesodermal origin and releases steroidal hormones, while the inner medulla is derived from ectoderm and secretes adrenergic neurotransmitters (also known as catecholamines). In the 5th developmental week, mesothelial cells enter the mesenchymal layer. Subsequently, large acidophilic cells differentiate, forming a primitive cortex. Smaller cells then migrate and engulf the acidophilic cells; these will go on to form the definitive cortex. Recommended video: What is a gland? A general definition of a gland and an overview of the major glands of the body. In the 7th developmental week, neural crest cells that are formed at the apex of the neural folds migrate (after the neural tube is completely closed) via a ventral pathway. These cells enter the gland from the medial face and subsequently differentiate into chromaffin cells that are organized centrally, in cords and masses. The chromaffin cells are so named because of the yellow-brown stain they produce after reacting with chromium based salts. Structure/function relationship Location and relations The left and right suprarenal glands differ slightly in their shape and location on top of their respective kidneys. The right gland is more pyramidal and sits on top of the upper pole of the kidney, while the left gland is more crescenteric and hangs more over the medial side of the left kidney, superior to the hilum.

17 The right adrenal gland rests on the diaphragm and the medial anterior portion is crossed by the inferior vena cava. While on the left side, the adrenal gland rests on the left crus of the diaphragm and the upper anterior surface is covered by the peritoneum. On both sides, the adrenal glands are enclosed in the renal fascia of Gerota, with a sheath of fascia separating it from its kidney. The Adrenal glands are easy to spot during a dissection. They look like two pyramids located in close proximity to the superior pole of each kidney.

18 The Histological Features Of The Adrenal cortex Essentially the gland is divided into three layers. However, only two of these layers are of homeostatic significance. There is an outer fatty capsule just deep to the renal fascia that functions as an added protective layer. Deep to the capsule, is the adrenal cortex. The cortex can be subdivided into the zona glomerulosa, the zona fasciculata and the zona reticularis. The zona glomerulosa is comprised of small rounded cells that are responsible for secreting mineralocorticoids such as aldosterone. Aldosterone regulates the uptake of water in the distal convoluted tubules, which consequently alters the bodys blood pressure. Zona fasciculata is significantly thicker than the other two cortical layers. It is made up of pale staining vacuolated cells arranged in parallel rows. This layer is responsible for secreting glucocorticoids to increase the overall blood glucose level in an effort to provide more energy for a system under stress. Finally, the zona reticularis consists of smaller cells that stain darker relative to cells of the aforementioned layers. Here, adrenal androgens are produced, which serve as precursors for testosterone.

19 The Histological Features Of The Adrenal cortex Hormones of the adrenal glands Adrenal medulla At the center of the organ is a thin, grey medulla. Residing here are chromaffin cells, splanchnic nerves and dilated capillaries. The chromaffin cells are responsible for the production of catecholamines, namely epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. Epinephrine is released directly into the medullary capillaries and carried to their site of action via systemic circulation. The physiological effect it has is dependent on the neuroreceptors present at the site at which the chemical acts. gland to synapse on the membranes of chromaffin cells.

20 The Histological Features Of The Adrenal Cortex Neurological supply The action of the adrenal gland is regulated both by neuronal and hormonal stimulation. The cortex is activated by adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. ACTH subsequently stimulates the respective cortical zones to produce corticosteroids. On the other hand, the adrenal medulla is innervated by type B (medium diameter, myelinated) preganglionic nerve fibers. These nerve fibers leave the intermediolateral cell column of the lateral horn of the spinal cord from the T5 – T8 segments of the spinal cord and bypass the paravertebral sympathetic ganglion chain. The fibers converge after bypassing the sympathetic trunk, forming the greater splanchnic nerve. Greater Splanchnic Nerve Some of these fibers will synapse at the celiac ganglion and post-synaptic fibers of the celiac ganglion will innervate the blood vessels supplying the suprarenal gland. Other fibers of the greater splanchnic nerve will bypass the celiac ganglion and enter the adrenalgland to synapse on the membranes of chromaffin cells.. For this reason, the adrenal medulla is sometimes considered as a neuroendocrine bridge between the two physiological segments. The chromaffin cells act as enlarged post-ganglionic fibers that release their neurochemicals directly into the blood stream instead of at a neuroeffector junction.

21 Vascular & Lymphatic System The adrenal glands receive arterial supply directly from the abdominal aorta as well as from the inferior phrenic arteries and the renal arteries. The inferior phrenic arteries leave the anterior surface of abdominal aorta just superior to the celiac trunk. Each inferior phrenic artery travels superolaterally and at the upper medial borders of the adrenal glands, they branch into several superior suprarenal arteries that enter the gland. Superior Suprarenal Arteries The middle suprarenal arteries branch directly from the anterolateral surface of the abdominal aorta, adjacent to the celiac trunk. These vessels travel horizontally and pierce the lower medial border of the adrenal glands by way of their branches. Middle Suprarenal Artery Also, each renal artery provides an inferior suprarenal artery that enters the inferior aspect of the gland. The left inferior suprarenal artery travels vertically and cranially towards the gland, while the right vessel travels more horizontally and obliquely towards its destination. Both glands return deoxygenated blood to the systemic circulation by way of a right and a left suprarenal vein. The right suprarenal vein takes a short horizontal course to drain directly into the inferior vena cava. However, the left suprarenal vein travels vertically to the renal vein, which then drains to the inferior vena cava. Lymphatic drainage is achieved by para-aortic lymph nodes. Suprarenal Vein.

22 The Macroscopic, the Microscopic Structure and The Functional Histological Structure of The Testis. The upper pole of the epididymis is attached high up on the posterolateral surface of the testis. Here there is a fibrous`mass, the mediastinum testis From which septa radiate to reach the tunica albuginea. The septa divide the testis into some 400 lobules, each of which contains two (sometimes three or four) highly convoluted seminiferous tubules. Each tubule is about 60 cm (2ft) long. The tubules lie rather loosely between the tunica albuginea and fibrous septa so that the cut surface of the organ bulges with herniating tubules. The seminiferous tubules open into the rete testis, which is a network of intercommunicating channels lying in the mediastinum testis. From the rete the vasa efferentia, 15 to 20 in number, enter the commencement of the canal of the epidymidis, thus attaching the head of the epidymidis to the testis.

23 Histological Features Of The Testis.

24 Histological sections of the mature testis are easily recognized. The dense fibrous tissue of the tunica albuginea is thick, and fibrous septa divide the field into loculi. The seminiferous tubules, convoluted within the loculi, are cut in multiple sections. Each tubule demonstrates several layers of cells. The outermost layer consists of spermatogonia, which divide to produce the cells of the next layer or two, the primary spermatocytes-the largest of the germ-cell series.These divide by meiosis, halving the chromosome number,to form secondary spermatocytes which are not commonly identified because they have a very short life and divide almost immediately to form spermatids.These do not divide but undergo a metamorphosis into spermatozoa.The whole process of producing spermatozoa from spermatogonia is spermatogenesis and takes between nine weeks to ten weeks on the average.The transformation of spermatids into spermatozoa is known as spermiogenesis.

25 Histological Features Of The Testis.

26 Different parts of a tubule demonstrate germ cells at different stages of development. Amongst the developing germ cells are the supporting or sustentacular cells of (Sertoli). By their many branching processes which adhere to one another (but not as a syncytium) they form an anastomosing network within which the germ cells are embedded, an arrangement that is only apparent on electron microscopy. The Sertoli cells secrete androgen binding protein (ABP) which keeps a high concentration of testosterone in the germ cell environment. In addition the Sertoli cells equally secretes MIH factor. Apart from spermatozoa, the testis makes a small contribution to semen (seminal fluid) probably about 10% but; most of the semen about (60%) comes from the seminal vesicle and the prostate about 30%. Scattered amongst the cells of the connective tissue between the tubules (outside them) are the interstitial cells (of Leydig). Larger than fibroblasts, they constitute the endocrine portion of the testis, secreting testosterone, the male sex hormone necessary for spermatogenesis.

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28 The Development and Descent of The Testis: By the end of the fourth month of fetal life the primitive testis (derived from the gonadal ridge medial to the mesonephric ridge of the intermediate mesodermal plate cell mass lies near the deep inguinal ring connected to that region of the anterior abdominal wall by a peritoneal fold. By the seventh month it is in the deep inguinal ring, and in the course of a few days during the next few weeks it progresses rapidly through the inguinal canal into the scrotum,this is the descent of the testis( the term does not mean that the movement of the testis down the posterior abdominal wall,the growth of the trunk carries the kidney and the suprarenal glands upwards,away from the testis.) An elongated diverticulum of the peritoneal cavity, the processus vaginalis has preceded the testis through the inguinal canal into the scrotum and the testis moves down behind this. The processus vaginalis normally becomes obliterated except at the lower end where the `testis bulges into it from behind and blends at its margin s to form the tunica albuginea. Of The so-called visceral layer of the tunica albuginea is testicular rather than coelomic in origin, in the same way that the surface epithelium of the ovary blends with the surrounding peritoneum (like the corneal epithelium with the conjunctiva)

29 Histological Features Of The Testis. Although the endocrine control and regulation of the descent of the testes is reasonably well defined, the mechanism of descent is still unclear. It appears that the enlarging epidymidis, attached to the testis before and during its descent assists to push the testis down. The descent of the testis into the scrotum is assisted by the gubernaculum (a mesodermal condensation at the lower end of the gonad) which swells by the imbibition of water to enlarge a passage for descent. Contrary to earlier opinions, the gubernaculum does not become attached to the bottom of the scrotum and does not pull the testis down. However, it does appear to play an important role, possibly by preventing the closure of the inguinal canal or directing the course of descent. Aberrant strands of gubernaculum may be associated with a testis in unusual sites (ectopic testis) in the inguinal or femoral regions or the perineum, but a causal relationship has not been established.

30 Failure to descend may result in cryptorchid testis,where it remains in the abdomen or descent may be arrested anywhere from the deep downwards.Undescended testes are peculiarly liable to malignant disease,spermatogenesis is equally defective in them, it may be that in some instances spermatogenesis is entirely absent in them while androgenic activity is unaffected.Undescended testis must be distinguished from retracted testes,where the cremaster muscle draws them back into the canal,especially in the young under the influence of cold ambient temperature. Failure of obliteration of the whole processus vaginalis gives rise to the congenital type on indirect inguinal hernia, localized persistence of part of the processus forms the encysted hydrocele of the cord. In the much commoner hydrocele of the testis, fluid fills the cavity of the tunica vaginalis.

31 Cryptorchidism The failure of a single testis or both testes to descend into the scrotum is known as cryptorchidism. Although many infants may be cryptorchid at birth, the testes may spontaneously descend by three months of age. If the testes have not descended by four to six months of age, they are brought down surgically (Orchidopexy). Individuals with cryptorchidism have a higher risk of developing testicular cancer and can become irreversibly sterile. Testes located in the abdomen are usually three to five degrees warmer than if they were in the scrotum. This can reduce the number of adult type A spermatogonia available for spermatogenesis while increasing the likelihood of promoting germ cells into carcinoma cells. Inguinal hernia and hydrocele Recall that the connection between the abdominal cavity and the processus vaginalis in the scrotum normally becomes obliterated. If it remains open, intestines may descend into the scrotum and cause congenital indirect inguinal hernia. In instances when the obliteration is incomplete, small fluid-secreting cysts may persist between the parietal and visceral layers of the tunica vaginalis, forming hydrocele of the testis and/or spermatic cord.

32 Macroscopic, Microscopical Anatomical and Functional Histological Aspects of The Ovary. The ovary consists of a fibrous stroma covered by a layer of cubical cells, the superficial epithelium, that was originally but mistakenly called the germinal epithelium; it has nothing to do with the formation of the primitive germ cells (the oogonia) which are derived in the early embryo from the endodermal cells of the hindgut the yolk sac that migrate laterally into the developing gonad. By mitosis and growth the oogonia become primary oocytes surrounded by granulosa cells derived from the stroma. A primary oocyte with a single layer of granulosa cells is a primary follicle; when the granulosa cells proliferate to form more than one layer, the primary follicle becomes the secondary follicle. In a 5-month fetus there are about 6 million follicles, but many degenerate and by birth there one million reduced to about 40,000 by puberty. Each month during reproductive life a follicle grows and accumulates fluid (liquor folliculi), to become an ovarian (Graafian) follicle. The stromal cells surrounding the follicle forms the theca. Before ovulation the primary oocyte undergoes meiosis (halving the chromosome number) forming a secondary oocyte. It is this cell, commonly called the ovum that is discharged at ovulation. The liquor folliculi escapes and haemorrhage occurs into the collapsed follicle.The granulosa cells and some of the thecal cells now develop into a corpus luteum.This persists for one week if pregnancy does not occur,or for (9)-nine months if it does. At the end of either time it atrophies and becomes replaced by a fibrous scar, the corpus`albicans. Since only about 400 ova could be shed in the course of a reproductive, most oocytes and follicles are destined never to reach maturity, and they could undergo degeneration at any stage of their development, becoming known as atretic follicles.

33 Development of The Ovaries: The Ovary develops from the paramesonephric ridge of the intermediate mesodermal plate cell mass in the same way as the testis. Its site of origin lies in the peritoneum of the posterior abdominal wall. It descends, preceded by the gubernaculum through the inguinal canal, as in the male, and becomes attached to the labium majus, however, the ovary does not follow its gubernaculum so far and its descent is arrested in the pelvis. The gubernaculum persists as the ligament of the ovary and the round ligament of the uterus. The ovary is supplied by its own branch from the dorsal aorta and drains into the subcardinal veins. As` with the testis, artery and vein persist, becoming merely elongated as the gonad descends to its adult position. The mesonephric tubules and mesonephric duct normally disappear in the female. However, should they persist their remnants are to be found between the layers of the broad ligament. The epoophoron consists of a number of tubules joining at right angles a persistent part of the mesonephric duct. It lies in the mesosalpinx between the ovary and the tube. The mesonephric duct may persist as a tube (duct of Gaertner) opening into the lateral fornix of the vagina or even at the vestibule of the uvula alongside the vaginal orifice. The paroophoron lies nearer the base of the broad ligament. It consists of a number of minute tubules, blind at each end, the homologue of the paradidymis in the male. Distension of such a tubule produces a parovarian cyst, characterized by its thin wall and crystal- clear fluid content.

34 The pancreas contains tissue with an endocrine and exocrine role, and this division is also visible when the pancreas is viewed under a microscope. The tissues with an endocrine role can be seen under staining as lightly- stained clusters of cells, called pancreatic islets (also called islets of Langerhans). Pancreatic islets contain alpha cells, beta cells, delta cells, and PP cells, each of which releases a different hormone. These cells have characteristic positions, with alpha cells (secreting glucagon) tending to be situated around the periphery of the islet, and beta cells (secreting insulin) more numerous and found in the centre. Islets are composed of up to 3,000 secretory cells, and contain several small arterioles and venules that allow the hormones secreted by the cells to enter the systemic circulation. The majority of pancreatic tissue has a digestive role. On staining, these darker- staining cells form clusters (Latin: acini), which are arranged in lobes that have thin fibrous walls. The cells of each acinus secrete inactive digestive enzymes called zymogens into small intercalated duct which they surround. Because of their secretory function, these cells have many small granules of zymogens that are visible. The intercalated ducts drain into larger ducts within the lobule, and finally interlobular ducts. The ducts are lined by a single layer of column-shaped cells. There is more than one layer of cells as the diameter of the ducts increases.

35 This image shows a pancreatic islet when pancreatic tissue is stained and viewed under a microscopy. Parts of the digestive ("exocrine") pancreas can be seen around the islet, more darkly. These contain hazy dark purple granules of inactive digestive enzymes (zymogens).

36 Variation The size of the pancreas varies considerably. Several anatomical variations exist, relating to the embryological development of the two pancreatic buds. The pancreas develops from these buds on either side of the duodenum. The ventral bud eventually rotates to lie next to the dorsal bud, eventually fusing. If the two buds, each having a duct, do not fuse, a pancreas may exist with two separate ducts, a condition known as a pancreas divisum. This condition has no physiologic consequence. If the ventral bud does not fully rotate, an annular pancreas may exist. This is where sections of the pancreas completely encircle the duodenum, and may even lead to duodenal atresia. An accessory pancreatic duct may exist if the main duct of the pancreas does not regress. Variations In The Anatomy O9f The Pancreas

37 Legend For The Pancreas & Its Surrounding Structures

38 A pancreatic islet that uses fluorescent antibodies to show the location of different cell types in the pancreatic islet. Antibodies against glucagon, secreted by alpha cells, show their peripheral position. Antibodies against insulin, secreted by beta cells, show the more central position that these cells tend to have.

39 Gene and Protein Expression. 10,000 protein coding genes (50% of all genes) are expressed in the normal human pancreas. Less than 100 of these genes are more specifically expressed in the pancreas. Similar to the salivary glands, most of the pancreas specific genes encode for secreted proteins. Corresponding pancreas specific proteins are either expressed in the exocrine cellular compartment and have functions related to digestion of food uptake such as digestive chymotrypsinogen enzymes and pancreatic lipase PNLIP, or expressed in the various cells of the endocrine pancreatic islets and have functions related to secreted hormones such as insulin, glucagon, somatostatin and pancreatic polypeptide.

40 Embryonic Development Of The Pancreas As part of embryonic development, the pancreas forms as two buds from the foregut, an embryonic tube that is a precursor to the gastrointestinal tract. It is therefore of endodermal origin. Pancreatic development begins with the formation of a dorsal and ventral pancreatic bud. Each joins with the foregut through a duct. The dorsal pancreatic bud forms the neck, body, and tail of the developed pancreas, whereas the ventral pancreatic bud forms the head and uncinate process. The definitive pancreas results from rotation of the ventral bud and the fusion of the two buds. The rotation of the ventral bud occurs in tandem with the duodenum, which also rotates to the right Upon reaching its final destination, the ventral pancreatic bud fuses with the much larger dorsal pancreatic bud. At this point of fusion, the main ducts of the ventral and dorsal pancreatic buds fuse, forming the main pancreatic duct. The duct of the dorsal bud regresses, leaving the main pancreatic duct.

41 Pancreas Of A Human Embryo At The End Of Sixth Week Of Gestation.

42 Embryonic Development Of The Pancreas The cells of the pancreas differentiate through two main pathways. In progenitor cells of the exocrine pancreas, important molecules that induce differentiation include follistatin, fibroblast growth factors, and activation of the Notch receptor system. Development of the exocrine acini progresses through three successive stages. These are the predifferentiated, protodifferentiated, and differentiated stages, which correspond to undetectable, low, and high levels of digestive enzyme activity, respectively. The multi-potent pancreatic progenitor cells have the capacity to differentiate into any of the pancreatic cells: acinar cells, endocrine cells, and ductal cells. These progenitor cells are characterized by the co-expression of the transcription factors PDX1 and NKX6-1. Under the influence of neurogenin-3 and ISL1, but in the absence of notch receptor signaling, these cells differentiate to form two lines of committed endocrine precursor cells. The first line, under the direction of a Pax gene, forms α- and γ- cells, which produce glucagon and pancreatic polypeptides, respectively. The second line, influenced by Pax-6, produces beta cells (β-) and delta cells (δ-), which secrete insulin and somatostatin, respectively. Insulin and glucagon can be detected in the human fetal circulation by the fourth or fifth month of fetal development.

43 The Pancreas Originates From The Foregut, A Precursor Tube To Part Of The Digestive Tract, As A Dorsal & Ventral Bud. As It Develops, The Ventral Bud Rotates To The Other Side & The Two Buds Fuse Together.

44 Function The pancreas is involved in blood sugar control and metabolism within the body, and also in the secretion of substances (collectively pancreatic juice) which help digestion. These are divided into an "endocrine" role, relating to the secretion of insulin and other substances within pancreatic islets and helping control blood sugar levels and metabolism within the body, and an "exocrine" role, relating to the secretion of enzymes involved in digesting substances from outside of the body. Blood glucose regulation THROUGH The Pancreatic islets The pancreas maintains constant blood glucose levels. When the blood glucose level is too high, the pancreas secretes insulin and when the level is too low, the pancreas secretes glucagon. Cells within the pancreas help to maintain blood sugar levels (homeostasis). The cells that do this are located within the pancreatic islets that are present throughout the pancreas. When blood glucose levels are low, alpha cells secrete glucagon, which increases blood glucose levels. When blood glucose levels are high beta cells secrete insulin to decrease glucose in blood. Delta cells in the islet also secrete somatostatin which decreases the release of insulin and glucose. Glucagon acts to increase glucose levels by promoting the creation of glucose and the breakdown of glycogen to glucose in the liver. It also decreases the uptake of glucose in fat and muscle. Glucagon release is stimulated by low blood glucose or insulin levels, and during exercise.

45 Histology&Embryonic Development, The Pancreas Insulin acts to decrease blood glucose levels by facilitating uptake by cells (particularly skeletal muscle), and promoting its use in the creation of proteins, fats and carbohydrates. Insulin is initially created as a precursor form called preproinsulin. This is converted to proinsulin and cleaved by C-peptide to insulin which is then stored in granules in beta cells. Glucose is taken into the beta cells and degraded. The end effect of this is to cause depolarisation of the cell membrane which stimulates the release of the insulin. Activity of the cells in the islets is also affected by the autonomic nervous system. Sympathetic (adrenergic) α2: decreases secretion from beta cells, increases secretion from alpha cells, β2: increases secretion from beta cells Parasympathetic (muscarinic) M3: increases stimulation of alpha cells and beta cells

46 The pancreas has a role in digestion, highlighted here. Ducts in the pancreas (green) conduct digestive enzymes into the duodenum. This image also shows a pancreatic islet, part of the endocrine pancreas, which contains cells responsible for secretion of insulin and glucagon

47 Histology&Embryonic Development, The Pancreas The pancreas plays a vital role in the digestive system. It does this by secreting a fluid that contains digestive enzymes into the duodenum, the first part of the small intestine that receives food from the stomach. These enzymes help to break down carbohydrates, proteins and lipids (fats). This role is called the "exocrine" role of the pancreas. The cells that do this are arranged in clusters called acini. Secretions into the middle of the acinus accumulate in intralobular ducts, which drain to the main pancreatic duct, which drains directly into the duodenum. About L of fluid are secreted in this manner every day.

48 Histology&Embryonic Development, The Pancreas The cells in each acinus are filled with granules containing the digestive enzymes. These are secreted in an inactive form termed zymogens or proenzymes. When released into the duodenum, they are activated by the enzyme enterokinase present in the lining of the duodenum. The proenzymes are cleaved, creating a cascade of activating enzymes. Enzymes that break down proteins begin with activation of trypsinogen to trypsin. The free trypsin then cleaves the rest of the trypsinogen, as well as chymotrypsinogen to its active form chymotrypsin. Enzymes secreted involved in the digestion of fats include lipase, phospholipase A2, lysophospholipase, and cholesterol esterase.

49 Histology&Embryonic Development, The Pancreas Enzymes that breakdown starch and other carbohydrates include amylase. These enzymes are secreted in a fluid rich in bicarbonate. Bicarbonate helps maintain an alkaline pH for the fluid, a pH in which most of the enzymes act most efficiently, and also helps to neutralise the stomach acids that enter the duodenum. Secretion is influenced by hormones including secretin, cholecystokinin, and VIP, as well as acetylcholine stimulation from the vagus nerve. Secretin is released from the S cells which form part of the lining of the duodenum in response to stimulation by gastric acid. Along with VIP, it increases the secretion of enzymes and bicarbonate. Cholecystokinin is released from Ito cells of the lining of the duodenum and jejunum mostly in response to long chain fatty acids, and increases the effects of secretin. At a cellular level, bicarbonate is secreted from the acinar cells through a sodium and bicarbonate cotransporter that acts because of membrane depolarisation caused by the cystic fibrosis transmembrane conductance regulator. Secretin and VIP act to increase the opening of the cystic fibrosis transmembrane conductance regulator, which leads to more membrane depolarisation and more secretion of bicarbonate.

50 Legend For The Duodenum & Pancreas On Deep Dissection.

51 Clinical significance Pancreatic disease Inflammation Pancreatitis Clinical significance Pancreatic disease Inflammation Pancreatitis Inflammation of the pancreas is known as pancreatitis. Pancreatitis is most often associated with recurrent gallstones or chronic alcohol use, with other common causes including traumatic damage, damage following an Endoscopic Retrograde Cholangio- Pancreatograpy (ERCP), some medications, infections such as mumps and very high blood triglyceride levels. Acute pancreatitis is likely to cause intense pain in the central abdomen, that often radiates to the back, and may be associated with nausea or vomiting. Severe pancreatitis may lead to bleeding or perforation of the pancreas resulting in shock or a systemic inflammatory response syndrome, bruising of the flanks or the region around the belly button. These severe complications are often managed in an intensive care unit.

52 Digestive Function Of The Pancrease A variety of mechanisms act to ensure that the digestive action of the pancreas does not act to digest pancreatic tissue itself. These include the secretion of inactive enzymes (zymogens), the secretion of the protective enzyme trypsin inhibitor, which inactivates trypsin, the changes in pH that occur with bicarbonate secretion that stimulate digestion only when the pancreas is stimulated, and the fact that the low calcium within cells causes inactivation of trypsin. Additional functions The pancreas also secretes VIP and pancreatic polypeptide. Enterochromaffin cells secrete the hormones motilin, serotonin and substance P.

53 Clinical Significance. In pancreatitis, enzymes of the exocrine pancreas damage the structure and tissue of the pancreas. Detection of some of these enzymes, such as amylase and lipase in the blood, along with symptoms and findings on medical imaging such as ultrasound or a CT scan, are often used to indicate that a person has pancreatitis. Pancreatitis is often managed medically with pain reliefs, and monitoring to prevent or manage shock, and management of any identified underlying causes. This may include removal of gallstones, lowering of blood triglyceride or glucose levels, the use of corticosteroids for autoimmune pancreatitis, and the cessation of any medication triggers.

54 Chronic Pancreatitis Chronic pancreatitis refers to the development of pancreatitis over time. It shares many similar causes, with the most common being chronic alcohol use, with other causes including recurrent acute episodes and cystic fibrosis. Abdominal pain, characteristically relieved by sitting forward or drinking alcohol, is the most common symptom. When the digestive function of the pancreas is severely affected, this may lead to problems with fat digestion and the development of steatorrhoea; when the endocrine function is affected, this may lead to diabetes. Chronic pancreatitis is investigated in a similar way to acute pancreatitis. In addition to management of pain and nausea, and management of any identified causes (which may include alcohol cessation), because of the digestive role of the pancreas, enzyme replacement may be needed to prevent malabsorption.

55 Pancreatic cancers, particularly the most common type, pancreatic adenocarcinoma, remain very difficult to treat, and are mostly diagnosed only at a stage that is too late for surgery, which is the only curative treatment. Pancreatic cancer is rare in those younger than 40, and the median age of diagnosis is 71. Risk factors include chronic pancreatitis, older age, smoking, obesity, diabetes, and certain rare genetic conditions including multiple endocrine neoplasia type 1, hereditary nonpolyposis colon cancer and dysplastic nevus syndrome among others. About 25% of cases are attributable to tobacco smoking,while 5–10% of cases are linked to inherited genes. Pancreatic adenocarcinoma is the most common form of pancreatic cancer, and is cancer arising from the exocrine digestive part of the pancreas. Most occur in the head of the pancreas. Symptoms tend to arise late in the course of the cancer, when it causes abdominal pain, weight loss, or yellowing of the skin (jaundice). Jaundice occurs when the outflow of bile is blocked by the cancer. Other less common symptoms include nausea, vomiting, pancreatitis, diabetes or recurrent venous thrombosis.Pancreatic cancer is usually diagnosed by medical imaging in the form of an ultrasound or CT scan with contrast enhancement. An endoscopic ultrasound may be used if a tumour is being considered for surgical removal, and biopsy guided by ERCP or ultrasound can be used to confirm an uncertain diagnosis.

56 Pancreatic cancer, shown here, most commonly occurs as an adenocarcinoma in the head of the pancreas. Because symptoms (such as skin yellowing, pain, or itch) do not occur until later in the disease, it often presents at a later stage and has limited treatment options.

57 Histology&Embryonic Development, The Pancreas Because of the late development of symptoms, most cancer presents at an advanced stage.Only % of tumours are suitable for surgical resection.As of 2018, when chemotherapy is given the FOLFIRINOX regimen containing fluorouracil, irinotecan, oxaliplatin and leucovorin has been shown to extend survival beyond traditional gemcitabine regimens. For the most part, treatment is palliative, focus on the management of symptoms that develop. This may include management of itch, a choledochojejunostomy or the insertion of stents with ERCP to facilitate the drainage of bile, and medications to help control pain. In the United States pancreatic cancer is the fourth most common cause of deaths due to cancer. The disease occurs more often in the developed world, which had 68% of new cases in 2012.Pancreatic adenocarcinoma typically has poor outcomes with the average percentage alive for at least one and five years after diagnosis being 25% and 5% respectively. In localized disease where the cancer is small (< 2 cm) the number alive at five years is approximately 20%.

58 Histology&Embryonic Development, The Pancreas There are several types of pancreatic cancer, involving both the endocrine and exocrine tissue. The many types of pancreatic endocrine tumors are all uncommon or rare, and have varied outlooks. However the incidence of these cancers has been rising sharply; it is not clear to what extent this reflects increased detection, especially through medical imaging, of tumors that would be very slow to develop. Insulinomas (largely benign) and gastrinomas are the most common types. For those with neuroendocrine cancers the number alive after five years is much better at 65%, varying considerably with type. A solid pseudopapillary tumour is a low-grade malignant tumour of the pancreas of papillary architecture that typically afflicts

59 Diabetes Mellitus Type 1 Diabetes-Diabetes Mellitus Type 1 Diabetes mellitus type 1 is a chronic autoimmune disorder in which the immune system attacks the insulin-secreting cells of the pancreas. Insulin is needed to keep blood sugar levels within optimal ranges, and its lack can lead to high blood sugar. As an untreated chronic condition, diabetic neuropathy can result. In addition, if there is not enough insulin for glucose to be used within cells, the medical emergency diabetic ketoacidosis, which is often the first symptom that a person with type 1 diabetes may have, can result. Type 1 diabetes can develop at any age but is most often diagnosed before adulthood. For people living with type 1 diabetes, insulin injections are critical for survival. An experimental procedure to treat type 1 diabetes is the transplantation of pancreatic islet cells from a donor into the patient's liver so that the cells can produce the deficient insulin.

60 Type 2 Diabetes Diabetes Mellitus Type 2 Diabetes mellitus type 2 is the most common form of diabetes. The causes for high blood sugar in this form of diabetes usually are a combination of insulin resistance and impaired insulin secretion, with both genetic and environmental factors playing an important role in the development of the disease. The management of type 2 diabetes relies on a series of changes in diet and physical activity with the purpose of reducing blood sugar levels to normal ranges and increasing insulin sensitivity. Biguanides such as metformin are also used as part of the treatment along with insulin therapy. Others It is possible for one to live without a pancreas, provided that the person takes insulin for proper regulation of blood glucose concentration and pancreatic enzyme supplements to aid digestion. Pancreas transplant refers to a transplant of a pancreas.