The Endocrine System

Transcription

1 د.محمد حسین Histlgy The Endcrine System Is a grup f glands that regulate physilgical functins by releasing hrmnes int the bld stream. Intercellular signaling is the way by which a cell exerts its effects n anther cell ( r n itself ) and it subdivided int the fllwing classificatins: 1) Intracrine signals are prduced within the target cell. 2) Autcrine signals target the cell itself. 3) Juxtacrine signals target adjacent (tuching) cells. 4) Paracrine signals target cells in the vicinity f the emitting cell ( e.g. neurtransmitters) 5) Endcrine signals target distant cells by prducing hrmnes that travel thrugh the bld t reach all parts f the bdy. The endcrine system includes: 1. Endcrine glands, such as the pituitary, thyrid and parathyrid, adrenal, and the pineal gland; 2. Clusters f endcrine cells lcated in the rgans such as islets f Langerhans in the pancreas; and 3. Islated endcrine cells in certain tissues, such as the enterendcrine cells in the epithelium f the respiratry and digestive tracts. The rgans r tissues that are activated by released hrmnes are called target rgans r tissues. The cells in the target rgan/tissue have apprpriate receptrs, which are able t recgnize and respnd t specific hrmnes. Hrmne: a chemical substance prduced in the bdy that cntrls and regulates the activity f certain cells r rgans. The hrmnes can be divided int three classes based n their structure: 1. Sterid hrmnes are lipid hrmnes that have the characteristic ring structure f sterids and are frmed frm chlesterl. ( e.g. estrgen, teststerne, crtisne, and aldsterne ). 2. Peptide hrmnes are cmpsed f amin acids. The majrity f hrmnes f this type are secreted by the pituitary gland ( ACTH, TSH, FSH, GH, and prlactin) and parathyrid glands (PTH). 3. Amine hrmnes are derived frm the amin acid tyrsine.(e.g. T3&T4 released by the thyrid and adrenaline & nradrenaline secreted by the adrenal medulla). 1

2 د.محمد حسین Histlgy The pituitary gland is a neurendcrine rgan lcated inside the skull (in the sella turcica f the sphenid bne) and cnsidered a part f the brain. It weighs abut 0.5 g in adults &has dimensins f abut 10 x 13 x 6 mm. Embrygenesis: The hypphysis develps partly frm ral ectderm and partly frm nerve tissue. The neural cmpnent arises as an evaginatin frm the flr f the diencephaln and grws caudally as a stalk withut detaching itself frm the brain. The ral cmpnent arises as an ut pcketing f ectderm frm the rf f the primitive muth f the embry and grws cranially, frming a structure called hypphyseal (Rathke's) puch. Later, a cnstrictin at the base f this puch separates it frm the ral cavity. At the same time, its anterir wall thickens, reducing the lumen f Rathke's puch t a small fissure. Because f its dual rigin, the pituitary actually cnsists f tw glands 1. The psterir Neurhypphysis 2. The anterir Adenhypphysis United anatmically but with different functins. The Neurhypphysis cnsists f : a) Pars Nervsa b) Infundibulum i. Stalk ii. Median eminence. The Adenhypphysis: a) Pars Distalis ( Anterir Lbe) b) Pars Tuberalis c) Pars Intermedia. 2

3 د.محمد حسین Histlgy Bld Supply & the Hypthalam-Hypphyseal Prtal System: The bld supply f the hypphysis derives frm the internal cartid artery: Frm abve, the superir hypphyseal arteries supply the median eminence and the neural stalk; Frm belw, inferir hypphyseal arteries prvide bld mainly fr the neurhypphysis, with a small supply t the stalk. The superir hypphyseal arteries frm a primary capillary netwrk irrigating the stalk and median eminence. The capillaries then rejin t frm venules that branch again as a larger secndary capillary netwrk in the adenhypphysis, Capillaries f bth netwrks are fenestrated. In the HHPS there are three grups f hrmnes released at three sites : 1. Peptide hrmnes synthesized by neurns in the hypthalamus (the supraptic and the paraventricular nuclei) underg axnal transprt and accumulate distally in these axns, which are situated in the pars nervsa. 2. Anther grup f peptides is prduced by neurns in ther hypthalamic nuclei and carried in axns fr temprary axnal strage and secretin in the median eminence. Then enter the capillaries f the primary plexus and are transprted t the adenhypphysis where they diffuse amng endcrine cells and cntrl hrmne release frm their target cells. 3. The third grup f hrmnes cnsists f prteins and glycprteins released frm the endcrine cells f the adenhypphysis (under the cntrl f the neurpeptides just mentined) and picked up by capillaries f the secndary plexus, frm which they enter the general circulatin. 3

4 د.محمد حسین Histlgy Adenhypphysis (Anterir Pituitary) Pars Distalis ( anterir lbe) It accunts fr 75% f the mass f the hypphysis, it mainly cnsists f crds f epithelial cells (hrmne -secreting cells) interspersed with fenestrated capillaries. With few fibrblasts prducing reticular fibers that supprt these crds. These secretry cells are classified as Chrmphbes and Chrmphils. The Chrmphbes d nt effectively take a stain, s they appear clear in the Mallry trichrme stain. These cells are undifferentiated cells but are capable f differentiating int chrmphils. The Chrmphils include: Basphils (appear blue in Mallry stain) and Acidphils (appear red in Mallry stain) Subtypes f basphilic and acidphilic cells are identified by TEM r mre easily by IHC and are named fr their specific hrmnes r target cells. Acidphils include the smattrpic and mammtrpic cells, while the Basphilils are the gnadtrpic, crtictrpic, and thyrtrpic cells. Pars Tuberalis The pars tuberalis is the neck f the adenhypphysis; it wraps arund the infundibular stalk f the pituitary gland. It cntains a rich capillary netwrk and sme lw clumnar basphilic cells that are cmmnly arranged in crds. Mst f the cells f the pars tuberalis are basphilic gnadtrpic cells that secrete flliclestimulating hrmne (FSH) and luteinizing hrmne (LH). Pars Intermedia The pars intermedia, which develps frm the drsal prtin f Rathke's puch is (in humans) a rudimentary regin made up f crds and fllicles f weakly basphilic cells that cntain small secretry granules. Melancyte stimulating hrmne (MSH) is prbably prduced in the intermediate zne, and prbably als by basphils f the pars distalis. MSH increases melancyte activity and cells f the pars intermedia are ften referred t as melantrpic cells, but the verall physilgical significance f this regin remains uncertain, especially in adults. 4

5 د.محمد حسین Histlgy Cntrl f Secretin in the Adenhypphysis: The activities f the cells f the anterir pituitary are cntrlled primarily by peptide hrmnes prduced in hypthalamic nuclei and stred in their axns that run t the median eminence. Mst f these hrmnes are hypthalamic-releasing hrmnes; liberated frm the axns, they are transprted by capillaries t the pars distalis where they stimulate hrmne synthesis and/r release. Tw f the hypthalamic factrs, hwever, act t inhibit hrmne release by specific cells f the pars distalis (hypthalamic-inhibiting hrmnes). Anther mechanism is negative feedback by hrmnes frm the target rgans n secretin f the relevant hypthalamic factrs and n hrmne secretin by the relevant pituitary cells. Finally, hrmne secretin in the pars distalis is affected by ther hrmnes frm utside the feedback lp r even utside the majr target tissues. Examples: inhibin and activin prduced in the gnads, cntrl release f FSH and LH; the xytcin, liberated in the psterir pituitary in the curse f breast feeding, which increases secretin f prlactin. Neurhypphysis (Psterir Pituitary) The pars nervsa, des nt cntain secretry cells. It is cmpsed f neural tissue, cntaining unmyelinated axns f secretry neurns whse cell bdies situated in the supraptic and paraventricular nuclei f the hypthalamus. Als present are highly branched glial cells called pituicytes that resemble astrcytes and are the mst abundant cell type in the psterir pituitary. The secretry neurns (in hypthalamus) have larger diameter axns and well-develped synthetic cmpnents related t the prductin f hrmnes vaspressin (als called antidiuretic hrmne, ADH) and xytcin. These hrmnes are transprted axnally int the pars nervsa and accumulate in axnal dilatins called neursecretry bdies r Herring bdies, visible in the LM as faintly esinphilic structures. These bdies cntain numerus membrane-enclsed granules with either xytcin r vaspressin bund t a carrier prtein called neurphysin I and II respectively. Nerve impulses alng the axns trigger the release f the peptides frm the neursecretry bdies fr uptake by the fenestrated capillaries f the pars nervsa and the hrmnes are then distributed t the general circulatin. Axns frm the supraptic nuclei are mainly cncerned with vaspressin secretin, whereas mst f the fibers frm the paraventricular nuclei are cncerned with xytcin secretin. 5

6 د.محمد حسین Histlgy CLINICAL CORRELATION Pituitary Adenmas Pituitary adenmas are benign tumrs f the anterir pituitary gland. Clinically, they can be divided int nnsecreting and secreting frms. Histrically, adenmas were classified by their staining prperties, the degree t which they tk up the H&E stains. They were classified as basphilic, acidphilic, r chrmphbic adenmas. With mdern immuncytchemical techniques, hwever, tumr cells can be classified by the type f hrmne they prduce. Sme cells d nt mark with any antibdy, and their tumrs are called null-cell adenmas. Classificatin by secretry status may reflect, fr example, excess crtisl (Cushing disease) r prlactin (prlactinma) r the verprductin f grwth hrmne (gigantism r acrmegaly). A bitempral hemianpia is cmmnly seen in patients suffering frm cmpressin f the ptic nerve. ADRENAL GLAND The adrenal (suprarenal) glands are paired rgans that lie near the superir ples f the kidneys. They are flattened structures with a half-mn shape, abut 4 6 cm lng, 1 2 cm wide, and 4 6 mm thick in adults. Tgether they weigh abut 8 g. Each gland cvered by a dense cnnective tissue capsule that sends thin septa t the interir f the gland as trabeculae. The strma cnsists mainly f a rich netwrk f reticular fibers that supprt the secretry cells. The gland cnsists f tw cncentric layers: A yellwish peripheral layer, the Adrenal Crtex(AC), and A reddish-brwn central layer, the Adrenal Medulla (AM). The AC & AM are 2 rgans with distinct rigins, functins, and mrphlgy that becme united during embrynic develpment. They arise frm different embrynic germ layers: The AC arises frm mesderm and The AM derived frm the neural crest. 6

7 د.محمد حسین Histlgy Bld Supply The adrenals are supplied by several arteries that enter at varius pints arund their periphery. The branches f these arteries frm three grups: thse supplying the capsule; the crtical arteriles, which quickly frm capillaries and sinusids that irrigate all cells f the crtex and eventually jin the medullary capillaries; and medullary arteriles, which pass directly thrugh the crtex and frm an extensive capillary netwrk in the medulla. The cells f the adrenal medulla, thus, receive bth arterial bld frm the medullary arteries and venus bld riginating frm capillaries f the crtex. The capillary and sinusidal endthelium is highly attenuated and fenestrated. Capillaries f bth the crtex and the medulla frm the central medullary veins, which jin t leave the gland as the adrenal r suprarenal vein. Adrenal Crtex Cells f the AC have characteristic features f sterid-secreting cells. These include: (1) Central nuclei and acidphilic cytplasm, usually rich in lipid drplets. (2) Their cytplasm have prfuse SER f intercnnected tubules, which cntain the enzymes fr chlesterl synthesis and cnversin f the sterid prhrmne pregnenlne int specific active sterid hrmnes. (3) The mitchndria are ften spherical, with tubular rather than shelf like cristae cntaining the enzymatic equipment fr cnverting chlesterl t pregnenlne and fr sme steps in sterid hrmne synthesis. Sterid hrmne-secreting cells d nt stre their prduct in granules; rather, they synthesize and secrete sterid hrmnes upn demand. Sterids (being LMW lipidsluble mlecules) diffuse thrugh the plasma membrane and d nt require the specialized prcess f excytsis fr their release. 7

8 د.محمد حسین Histlgy The adrenal crtex has three cncentric znes in which the crds f epithelial cells are arranged smewhat differently and are specialized t prduce different classes f sterid hrmnes: I. Immediately inside the cnnective tissue capsule is the zna glmerulsa, cnsisting f clsely packed, runded r arched crds f clumnar r pyramidal cells surrunded by many capillaries and cmprising abut 15% f the crtex. II. The middle zne, the zna fasciculata, ccupies 65 80% f the crtex and cnsists f lng crds f large plyhedral cells, ne r tw cells thick, separated by fenestrated sinusidal capillaries. The cells are mst densely filled with cytplasmic lipid drplets and, as a result f lipid disslutin during tissue preparatin, ften appear vaculated r spngy in cmmn histlgical preparatins. Because f their vaculizatin, the cells f the fasciculata are als called spngycytes. III. The innermst zna reticularis cmprises abut 10% f the crtex and cntacts the adrenal medulla. It cnsists f smaller cells dispsed in a netwrk f irregular crds interwven with wide capillaries. The cells are usually mre heavily stained than thse f the ther znes because they cntain fewer lipid drplets and mre lipfuscin pigment. Crtical Hrmnes & Their Actins: The main prduct f the Z.G is a mineralcrticid called aldsterne; the Z. F and pssibly the Z.R secrete gluccrticids, especially crtisl; the Z. R prduces dehydrepiandrsterne (DHEA), a weak andrgen. The mineralcrticids, s called because they affect uptake f Na+, K+, and water by epithelial cells. The principal prduct is aldsterne, the majr regulatr f salt balance, which acts t stimulate Na+ reabsrptin in the distal cnvluted tubules f the kidneys. Aldsterne secretin in the zna glmerulsa is stimulated primarily by angitensin II and als by an increase in plasma K+ cncentratin, but nly weakly by ACTH. The gluccrticids, especially crtisl, affect CHO metablism by stimulating prductin f glucse frm amin acids r fatty acids (glucnegenesis) in many cells and glucse cnversin int glycgen in the liver. Crtisl induces fat mbilizatin in subcutaneus adipse tissue and prtein breakdwn in muscle. Crtisl als suppresses many aspects f the immune respnse, including cytkine release and lymphpiesis. Secretin f gluccrticids in the Z.F is cntrlled by ACTH and negative feedback prprtinal t the cncentratin f circulating gluccrticids is exerted at bth the pituitary and hypthalamic levels. Cells f the Z.F als secrete small amunts f andrgens. DHEA is the nly sex hrmne that is secreted in significant physilgical quantities by the AC. It is a weak andrgen that circulates in the bld as a sulfate and exerts its actins after being cnverted int teststerne in several tissues. Secretin by these cells is als stimulated by ACTH and is under feedback regulatin with the pituitary and hypthalamus. 8

9 د.محمد حسین Histlgy Fetal Adrenal Crtex At birth in humans, the adrenal gland is larger than that f the adult and prduces up t 200 mg f crticsterids per day, twice that f an adult. At this age, a layer knwn as the fetal r prvisinal crtex, cmprising 80% f the ttal gland, is present between the thin permanent crtex and an underdevelped medulla. The fetal crtex is thick and cntains mstly crds f large, sterid-secreting cells under the cntrl f the fetal pituitary. The principal functin f the cells is secretin f sulfated DHEA which is cnverted in the placenta t active estrgens (and andrgens), which mstly enter the maternal circulatin. The fetal adrenal crtex is an imprtant part f a fetplacental unit which affects bth endcrine systems during pregnancy but whse physilgical significance remains largely unclear. After birth, the prvisinal crtex underges invlutin while the permanent crtex rganizes the three layers (znes) described abve. Adrenal Medulla The adrenal medulla is cmpsed f large, pale-staining plyhedral cells arranged in crds r clumps and supprted by a reticular fiber netwrk. A prfuse supply f sinusidal capillaries intervenes between adjacent crds and a few parasympathetic ganglin cells are present. Medullary parenchymal cells, knwn as chrmaffin cells, arise frm neural crest cells. Chrmaffin cells can be cnsidered mdified sympathetic pstganglinic neurns, lacking axns and dendrites and specialized as secretry cells. Unlike cells f the crtex, medullary chrmaffin cells cntain many electrn-dense granules fr hrmne strage and secretin. These granules cntain ne r the ther f the catechlamines, epinephrine(adrenalin) r nrepinephrine (nradrenaline). Ultrastructurally the granules f epinephrine-secreting cells are less electrn-dense and generally smaller than thse f nrepinephrine-secreting cells. Catechlamine, tgether with Ca2+ and ATP, are bund in a granular strage cmplex with a prteins called chrmgranins. Nrepinephrine-secreting cells are als fund in paraganglia (cllectins f catechlamine-secreting cells adjacent t the autnmic ganglia) and in varius viscera. The cnversin f NE t E ccurs nly in chrmaffin cells f the AM. Abut 80% f the catechlamine secreted frm the adrenalis epinephrine. Medullary chrmaffin cells are innervated by chlinergic endings f preganglinic sympathetic neurns, frm which impulses trigger hrmne release by excytsis. Epinephrine & nrepinephrine are released t the bld in large quantities during intense emtinal reactins, such as fright, and prduce vascnstrictin, increased bld pressure, changes in heart rate, and metablic effects such as elevated bld glucse. These effects facilitate varius defensive reactins t the stressr (the fight -r-flight respnse). During nrmal activity, the adrenal medulla cntinuusly secretes small quantities f the hrmnes. 9

10 د.محمد حسین Histlgy CLINICAL CORRELATION Because f the feedback mechanism f adrenal crtex cntrl, patients wh are treated with crticids fr lng perids shuld never stp taking these hrmnes suddenly: secretin f ACTH in these patients is inhibited, and thus the crtex will nt be induced t prduce crticids, causing a severe misbalance in the levels f sdium and ptassium. PhechrmcytmaS Are neplasms f the AM characterized by the prductin f catechlamines, such as epinephrine and nrepinephrine, which cause significant hypertensin, ften episdic, in affected patients. Grssly, mst f these tumrs are well circumscribed and range in size frm a few grams t kilgrams. Micrscpically, phechrmcytmas can have a diverse appearance, frm spindle cells t large, bizarre cells. The cells are ften arranged in nests, r cell packets called zellballen. Histlgic features alne d nt reliably separate benign tumrs frm malignant nes; therefre, the demnstratin f metastases is necessary t ascertain malignancy. Adrencrtical disrders Disrders f the AC can classified as hyperfunctinal r hypfunctinal. Tumrs f the adrenal crtex can result in excessive prductin f gluccrticids (Cushing syndrme) r aldsterne (Cnn syndrme). Cushing syndrme is mst ften (90%) due t a pituitary adenma that prduces excessive ACTH; it is rarely caused by adrenal hyperplasia r an adrenal tumr. Excessive prductin f adrenal andrgens has little effect in men. Hwever, hirsutism is seen in wmen, and preccius puberty (in bys) and virilizatin (in girls) are seen in prepubertal children. These adrengenital syndrmes are the result f several enzymatic defects in sterid metablism that cause increased bisynthesis f andrgens by the adrenal crtex. Adrencrtical insufficiency ( Addisn disease) is caused by destructin f the AC in sme diseases. The signs and symptms result frm failure f secretin f bth gluccrticids and mineralcrticids by the AC. Carcinmas f the AC are rare, but mst are highly malignant. Abut 90% f them prduce sterids. 10

11 د.محمد حسین Histlgy The pancreatic islets are cmpact spherical r egg-shaped masses f endcrine tissue embedded within the acinar excrine tissue f the pancreas. There are mre than 1 millin islets in the human pancreas, mst numerus in the tail f the gland, but they nly cnstitute 1 2% f the rgan's vlume. A very thin capsule f reticular fibers surrunds each islet, separating it frm the adjacent acinar tissue. Islets have the same embrynic rigin as the acinar tissue: (endderm). Each islet cnsists f plygnal r runded cells, smaller and mre lightly stained than the surrunding acinar cells, arranged in crds that are separated by a netwrk f fenestrated capillaries. Autnmic nerve fibers cntact sme f the endcrine cells and the bld vessels. Rutine stains r trichrme stains shw that mst islet cells are acidphilic r basphilic with fine cytplasmic granules. The majr hrmne-prducing islet cells are mst easily identified and studied by immunhistchemistry: i. Alfa r A cells secrete primarily glucagn and are usually lcated near the periphery f islets. ii. Beta r B cells prduce insulin, are lcated centrally in islets and are the mst numerus cell type. iii. Delta r D cells, secreting smatstatin, scattered and much less abundant. Insulin is a heterdimeric prtein and the ther tw hrmnes are smaller single-chain plypeptides. iv. A minr furth cell type, mre cmmn in islets lcated within the head f the pancreas, are F r PP cells, which secrete pancreatic plypeptide. Pancreatic islets als nrmally cntain a few enterchrmaffin cells, like thse f the digestive tract, which secrete ther plypeptidehrmnes having ther effects within the digestive system and which are als scattered in the pancreatic acini and ducts. See table: 20 4 in yur textbk 11

12 د.محمد حسین Histlgy CLINICAL CORRELATIO Type 1 diabetes mellitus is the mst cmmn type f diabetes in childhd and adlescence (65% f ttal cases). It is characterized by insulin deficiency and sudden nset f severe hyperglycemia, diabetic ketacidsis, and death if patients are left withut insulin treatment. Symptms als include plyuria, plydipsia, lethargy, and weight lss. The majr cause f the disease is autimmune destructin f the insulin-secreting beta cells in the islets f Langerhans by T cells and humral mediatrs ( TNF,interleukin-1, nitric xide). Type 2 diabetes mellitus is characterized by hyperglycemia with nrmal r elevated insulin levels. In type 2 DM, insulin is present, but insulin-sensitive tissues, such as skeletal muscle and adipse tissues, manifest resistance t the actin f insulin. Defects in beta cell functin als cntribute t the disease prcess. Type 2 DM generally has an insidius nset and typically affects adults. Risk factrs include genetic factrs and a strng assciatin with besity. Apprximately 85% f type 2 diabetes is assciated with besity. DIFFUSE NEUROENDOCRINE SYSTEM The enterchrmaffin cells scattered in bth the islets and small ducts f the pancreas are similar t thse f the digestive tract. Cllectively these dispersed cells, as well as similar cells in the respiratry mucsa, make up the diffuse neurendcrine system (DNES). Like the pancreatic islets, mst f these cells are derived frm enddermal cells f the embrynic gut. Cells f the DNES are als referred t as gastrenterpancreatic (GEP) endcrine cells. Many cells f the DNES are stained by slutins f chrmium salts and have therefre been called enterchrmaffin cells. Thse cells that stain with silver nitrate are smetimes called argentaffin cells. Thse DNES cells secreting sertnin r certain ther amine derivatives demnstrate amine precursr uptake and decarbxylatin and are ften referred t acrnymically as APUD cells. Such names are still widely used but have been largely replaced by letter designatins like thse used fr pancreatic islet cells. Whatever name is used, cells f the DNES are highly imprtant due t their rle in regulating mtility and secretins f all types within the digestive system. 12

13 د.محمد حسین Histlgy THYROID GLAND The thyrid gland, lcated in the cervical regin anterir t the larynx, cnsists f tw lbes united by an isthmus. It riginates in early embrynic life frm the fregut endderm near the base f the future tngue. Its functin is t synthesize the thyrid hrmnes: thyrxine (tetra-idthyrnine r T4) and tri-idthyrnine (T3), which are imprtant fr grwth, cell differentiatin, and cntrl f the BMR and O2 cnsumptin in cells f the bdy, and affect prtein, lipid, and CHO metablism. The parenchyma f the thyrid is cmpsed f millins f runded epithelial structures called fllicles. Each fllicle cnsists f a simple epithelium and a central lumen filled with a gelatinus substance called cllid. The thyrid is the nly endcrine gland in which a large quantity f secretry prduct is stred. Mrever, the accumulatin is utside the cells, in the cllid f the fllicles, which is als unusual. In humans there is sufficient hrmne in fllicles t supply the bdy fr up t three mnths with n additinal synthesis. Thyrid cllid cntains the large glycprtein thyrglbulin, the precursr fr the active thyrid hrmnes. The gland is cvered by a fibrus capsule, which sends septa dividing it int lbules and carrying bld vessels, nerves, and lymphatics. Fllicles are densely packed tgether, separated frm ne anther nly by sparse reticular cnnective tissue. This strma is very well vascularized with an extensive netwrk f fenestrated capillaries clsely surrunding the fllicles, which facilitates mlecular transfer between the fllicles and bld. Fllicular cells range in shape frm squamus t lw clumnar. The size and cellular features f fllicles vary with their functinal activity. Active glands have mre fllicles f lw clumnar epithelium; glands with mstly squamus fllicular cells are cnsidered hypactive. The fllicular epithelial cells have typical junctinal cmplexes apically and rest n a basal lamina. The cells exhibit rganelles indicating active prtein synthesis and secretin, as well as phagcytsis and digestin. The nucleus is generally rund and in the center f the cell. Basally the cells are rich in rugh ER and apically, facing the fllicular lumen, are Glgi cmplexes, secretry granules filled with cllidal material, large phagsmes and abundant lyssmes. The cell membrane f the apical ple has a mderate number f micrvilli. Mitchndria and ther cisternae f rugh ER are dispersed thrughut the cytplasm. 13

14 د.محمد حسین Histlgy Anther endcrine cell type, the parafllicular, r clear cell (C cell), is als fund inside the basal lamina f the fllicular epithelium r as islated clusters between fllicles. Parafllicular cells, derived frm neural crest cells migrating int the area f the embrynic fregut, are usually smewhat larger than fllicular cells and stain less intensely. They have a smaller amunt f rugh ER, large Glgi cmplexes, and numerus small granules cntaining plypeptide hrmne. These cells synthesize and secrete calcitnin, ne functin f which is t suppress bne resrptin by steclasts. Calcitnin secretin is triggered by elevated bld Ca2+ levels. Cntrl f Thyrid Functin The majr regulatr f the anatmic and functinal state f thyrid fllicles is TSH, which is secreted by the anterir pituitary. TSH increases the height f the fllicular epithelium and stimulates all stages f thyrid hrmne prductin and release. Thyrid hrmnes inhibit the release f TSH, maintaining an adequate quantity f T4 and T3 in the rganism. TSH receptrs are abundant n the basal cell membrane f fllicular cells. Secretin f TSH is als increased by expsure t cld and decreased by heat and stressful stimuli. Synthesis & Accumulatin f Hrmnes by Fllicular Cells Synthesis and accumulatin f hrmnes take place in fur stages: 1) Synthesis f thyrglbulin. 2) Uptake f idide frm the bld. 3) Activatin f idide. 4) Idinatin f the tyrsine residues f thyrglbulin. 14

15 د.محمد حسین Histlgy Liberatin f T 3 & T 4 When stimulated by TSH, thyrid fllicular cells take up cllid by endcytsis. The cllid within the endcytic vesicles is then digested by lyssmal enzymes. Hydrlysis f thyrglbulin results in T 4, T 3, diidtyrsine, and mnidtyrsine, which are liberated int the cytplasm. The free T 4 and T 3 crss the baslateral cell membrane and are discharged int the capillaries. Mnidtyrsine and diidtyrsine are nt secreted int the bld, and their idine is remved by a deidinase. The prducts f this enzymatic reactin (idine and tyrsine) are reused by the fllicular cells. T 4 is the mre abundant cmpund, cnstituting 90% f the circulating thyrid hrmne, althugh T 3 acts mre rapidly and is mre ptent. CLINICAL CORRELATION HYPOTHYROIDISM Hypthyridism in the fetus may present at birth as cretinism, characterized by arrested r retarded physical and mental develpment. Adult hypthyridism may result frm diseases f the thyrid gland (eg, due t defects in hrmne synthesis r release) r may be secndary t pituitary rhypthalamic failure. Autimmune diseases f the thyrid, such as Hashimt disease, may impair its functin, with cnsequent hypthyridism. A diet lw in idide hinders the synthesis f thyrid hrmnes, causing increased secretin f TSH and cmpensatry grwth f the thyrid gland, a cnditin knwn as idine deficiency giter. Giters are endemic in sme regins f the wrld, where dietary idide is scarce and additin f idide t table salt is n trequired. The signs and symptms related t hypthyridism include fatigue, increased sensitivity t cld, pale skin, cnstipatin, muscle pain and weakness, and weight gain. HYPERTHYROIDISM Hyperthyridism may be caused by a variety f thyrid diseases, f which the mst cmmn frm is Graves' disease, characterized by inflammatin and grwth f the extracular adipse tissue, which leads t the bulging f the eyes (exphthalms). In this thyrid disrder hyperfunctin is due t an autimmune respnse invlving antibdies t TSH receptrs. These antibdies can bind the receptrs n fllicular cells and act as lng-lasting thyrid stimulatrs, cntinuusly stimulating thyrid hrmne secretin and prducing many effects f hyperthyridism such as decreased bdy weight and accelerated heart rate. 15

16 د.محمد حسین Histlgy Parathyrid Gland The fur small parathyrid glands typically lie n the psterir surface f the thyrid gland and are separated frm the thyrid gland by a cnnective tissue capsule. Cnnective tissue septa with bld vessels divide each parathyrid gland int many incmplete lbules. The parathyrid glands are derived frm the endderm f pharyngeal puch 3 (the inferir glands) and puch 4 (the superir parathyrid glands). There are tw types f cells in the gland: chief (principle) cells and xyphilcells. Adipcytes are cmmnly fund in the glands in lder individuals. The chief cells are small plygnal cells with rund nuclei and pale-staining, slightly acidphilic cytplasm. Ultrastructurally the cytplasm is seen t be filled with irregularly shaped granules. These are secretry granules cntaining the plypeptide parathyrid hrmne (PTH). Much smaller, ften clustered, ppulatins f xyphil cells are smetimes present. These are much larger than the principal cells and are characterized by acidphilic cytplasm filled with abnrmally shaped mitchndria. Sme xyphil cells shw lw levels f PTH synthesis, suggesting these cells are transitinal derivatives frm chief cells. The xyphil cells appear at puberty, and their numbers increase with age. Their functins are unclear. Actin f Parathyrid Hrmne & Its Interrelatin with Calcitnin PTH binds t receptrs in steblasts. This is a signal fr these cells t prduce an steclast-stimulating factr, which increases the number and activity f steclasts and thus prmtes the absrptin f the calcified bne matrix and the release f Ca 2+ int the bld. The resulting increase in the cncentratin f Ca 2+ in the bld suppresses the prductin f PTH. Calcitnin frm the thyrid gland als influences steclasts by inhibiting bth their resrptive actin n bne and the liberatin f Ca 2+. Calcitnin thus lwers bld Ca 2+ cncentratin and increases stegenesis; its effect is ppsite t that f PTH. These tw hrmnes cnstitute a dual mechanism t regulate bld levels f Ca 2+, an imprtant factr in hmestasis. PTH indirectly increases the absrptin f Ca 2+ frm the GIT by stimulating the synthesis f vitamin D, which is necessary fr this absrptin. In additin t increasing the cncentratin f Ca 2+, PTH reduces the cncentratin f phsphate in the bld. This effect is a result f the activity f PTH n kidney tubule cells, diminishing the absrptin f phsphate and causing an increase f phsphate excretin in urine. The secretin f parathyrid cells is regulated by bld Ca 2+ levels. 16

17 د.محمد حسین Histlgy PINEAL GLAND The pineal gland, als knwn as the pineal bdy r epiphysis cerebri. It is a very small, pine cne-shaped rgan in the brain. It develps with the brain frm neurectdermin the rf f the diencephaln and is fund in the psterir f the third ventricle, attached t the brain by a shrt stalk. The gland is cvered by C.T f the pia mater, frm which emerge septa cntaining small bld vessels and dividing the gland in t lbules. It is cmpsed f tw types f cells: pinealcytes and Interstitial glial cells. The prminent and abundant secretry cells are the pinealcytes, which have slightly basphilic cytplasm and large, irregular euchrmatic nuclei and nucleli. Ultrastructurally pinealcytes are seen t have secretry vesicles, many mitchndria, and lng cytplasmic prcesses extending t the vascularized septa, where they end in dilatatins near capillaries, indicating an endcrine functin. These cells prduce melatnin, a LMW tryptphan derivative. Unmyelinated sympathetic nerve fibers enter the pineal gland and end amng pinealcytes, with sme frming synapses. Interstitial glial cells f the pineal gland stain psitively fr glial fibrillary acidic prtein and thus mst clsely resemble astrcytes. They have elngated nuclei mre heavily stained than thse f pinealcytes, lng cytplasmic prcesses, and are usually fund in perivascular areas and between the grups f pinealcytes. Pinealastrcytes represent nly abut 5% f the cells in the gland. A characteristic feature f the pineal gland is the presence f variusly sized cncretins f calcium and magnesium salts called crpra arenacea r brain sand, which frm by precipitatin arund extracellular prtein depsits. Such cncretins appear during childhd and gradually increase in number and size with age, with n apparent effect n the gland's functin. Accumulatins f brain sand are paque t x-rays and allw the pineal t serve as a gd midline marker in radilgical and CT studies f the brain. Rle f the Pineal Gland in Cntrlling Bilgical Cycles Melatnin release frm pinealcytes is prmted by darkness and inhibited by daylight and the resulting diurnal fluctuatin in bld melatnin levels induces rhythmic changes in the activity f the hypthalamus, pituitary gland, and ther endcrine tissues that characterize the circadian (24 hurs, day/night) rhythm f physilgical functins and behavirs. In humans and ther mammals the cycle f light and darkness is detected within the retinas and transmitted t the pinealcytes via the retinhypthalamic tract, the suprachiasmatic nucleus, and the tracts f sympathetic fibers entering the pineal. The pineal gland acts therefre as a neurendcrine transducer, cnverting nerve input regarding light and darkness int variatins in many hrmnal functins. The End 17