About 15% of cortex volume---Structure:LMsmall, low columnar:cellsor polygonalbe arranged into nests or clustersZona glomerulosadeep stained, round:nucleilight basophilic:cytoplasm---Function: secrete mineralocorticoid ( e.g. aldosterone) regulateelectrolyte and water balance
Zona fasciculataAbout 78% of cortex volume---Structure:LMclear margin，large:cellsbe arranged in straight cords: light stainingcytoplasm appear vacuolated (foamy---Functionsecrete glucocorticosteroid(e.g. cortisol、corticosterone ) and androgen (less)regulate carbohydrate, protein and lipid metabolisminfluence immune response
Zona reticularis7% of cortex volume---Structure:LM: polyhedral and small;cellsbe arranged in irregularanastomosing cordsacidophilic:cytoplasm---Function:secret androgen (testosterone) andsmall amount of estrogen
Functions ofminralocortiosterolsAldosterol regulation of water and electrolytes balace
Cortisol in inflammation and stress :naw just review the inflammatory prosessa)Release from the damaged cells the chemicals which activate the inflammation .b)Increase blood flow by chemicals .leakage large quanitaties of plasma .c)d) Infltration of leukcytes .e)Formation of fibrous tissue and healing .The big question here how the cortisol works as anti-inflammation ?When it adminstrated in large amount :1)It can block the early stages .2) Causes rapid resolution and increase the healing process .
1)It can block the early stages :a) Cortisol stabilizes the lysosomal membranes .b)Cortisol decreases the permeability of capillaries .c)Decrease migration of WBCand phagocytosis of damaged cells .d)Suppres immune system causing decrease lymphocytes production .e)Attenuates the fever by decreasing IL-1 .2)During the healing process :By increasing glucose , fats , aminoacids which reqaired by the cells
Unwanted effects related to cortisol :These effects occurs when it is administrated in large doses as we see in our lifeIncrease administration in large doses causesatrophy of all lymphoid tissues which in turndecrease the out put of T cells and antibodiesThis lead tofulminating infection and death
Adr. cellNoradr.cellEMelectron-densegranules%80:adrenaline celli. heart rateii. dilate blood vessel%20:celladrenalinenori. blood pressureii. the flow speed of blood---Function:secrete adrenaline and noradrenalinesecrete some polypeptides (galanin, neuropeptide Y, enkephalin)
) MEDULLA: Completely surrounded by the cortexMasses and branching cords of cells, surroundingfenestrated blood capillariesCELLS- mainly Chromaffin cells)- catecholamine-secreting cellsFew nerve cells are also found in the medulla.1.ChromaffinCells: Types- epinephrine and norepinephrine secreting cellsHard to differentiate between them in H & E preparationsLarge polyhedral cells + central round vesicular nucleiCytoplasm-Chromaffin granules-brown color-stain-chromiumsalts.. Golgi apparatus- well-developed RER-moderate amount Membrane-bounded granules- large number Granules- homogeneous in Epinephrine-secreting cell Electron-dense+ peripheral halo in Norepinephrine-secreting cells
CORTEX MEDULLAMesodermal in origin Ectodermal in originIt consists of 3 zones:glomerulosa,fasciculata &reticularis.It is formed ofchromaffin cells andnerve cells.It secretesmineralocorticoids,glucocorticoids andsex hormones.It secretesepinephrine &norepinephrine.It gives -vechromaffin reaction.It gives +vechromaffin reaction.It is supplied byarterial blood.It is supplied byarterial and venousblood.It is essential for life. Not essential for life.Differences between suprarenal cortex and medulla
2- Sympathetic Multipolar Nerve Cells:They are the cell bodies of sym~ neurons, which probablystimulate the secretory activity of the Medullary cellsFunctions of the Adrenal Medulla:Secretion of epinephrine and norepinephrine-periods of stress(e.g. fight, fright, flight),Histochemical Reactions of Suprarenal Medulla:They are the reactions given by the chromaffin cells due topresence of epinephrine& norepinephrine.a. Ferric chloride stains the medulla Green.b. Iodine stains the medulla red.c. Cramers reaction: Exposure of suprarenal gland to osmiumvapor, stain both cortex (due to fat) and medulla black.d. Chromaffin reaction: When fresh suprarenal gland is fixed inchromic acid or K dichromate, medulla accepts a brown color (+vechromaffin reaction).
Cushing Reaction. The so-called Cushing reaction is a special type ofCNS ischemic response that results from increase pressure of the cere-brospinal fluid around the brain in the cranil vault . For instance , whencerebrospinal fluid pressure rises to equal the arterial pressure , itcompresses the whole brain as well as the arteries in the brain and cutsIschemic response that causes the aterialoff the blood supply to theHas risen to a level higherpressure to rise.When the arterial pressurepressure, blood will flow once again intothan the cerebrospinal fluidthe brain to relieve the brain ischemia.thus bloob pressure comes toa new equilibrium level slightly higher than the cerebrospinal fluid pres.allowing blood to begin again to flow through the braincaused in this instance by pumping fluid under pressureinto the cranial vault around the brain. The Cushingreaction helps protect the vital centers of the brain fromloss of nutrition if ever the cerebrospinal fluid pressurerises high enough to compress the cerebral arteries
Hypersecretion by the adrenal cortex causes a complexcascade of hormone effects called Cushing’s syndrome.Most of the abnormalities of Cushing’s syndrome areascribable to abnormal amounts of cortisol, but excesssecretion of androgens may also cause importanteffects. Hypercortisolism can occur from multiplecauses, including (1) adenomas of the anterior pituitarythat secrete large amounts of ACTH, which then causesadrenal hyperplasia and excess cortisol secretion; (2)abnormal function of the hypothalamus that causes highlevels of corticotropin-releasing hormone (CRH),which stimulates excess ACTH release; (3) “ectopic
secretion” of ACTH by a tumor elsewhere in thebody such as an abdominal carcinoma; and (4)adenomas ofthe adrenal cortex. When Cushing’s syndrome issecondaryto excess secretion of ACTH by the anteriorpituitary, this is referred to as Cushing’s disease.(5)Cushing’s syndrome can also occur when largeamounts of glucocorticoids are administered overprolongedperiods for therapeutic purposes. For example,patients with chronic inflammationsuch as rheumatoid arthritis are often treated withglucocorticoids and may develop some of the clinicalsymptoms of Cushing’s syndrome
Administration of large doses of dexamethasone,a synthetic glucocorticoid, can be used to distinguishbetween ACTH-dependent and ACTH-independentCushing’s syndrome. In patients who have overproductionof ACTH due to an ACTH-secreting pituitaryadenoma or to hypothalamic-pituitary dysfunction,even large doses of dexamethasone usually do notsuppress ACTH secretion. In contrast, patients withprimary adrenal overproduction of cortisol (ACTHindependent)usually have low or undetectable levels ofACTH. The dexamethasone test, although widely used,can sometimes give an incorrect diagnosis, becausesome ACTH-secreting pituitary tumors respond todexamethasone with suppressed ACTH secretion.Therefore, it is usually considered to be a first step inthe differential diagnosis of Cushing’s syndrome.
Adrenal cortical adenoma. The adenoma is distinguished from nodularhyperplasia by its solitary, circumscribed nature. The functional status of an adrenalcorticaladenoma cannot be predicted from its gross or microscopic appearance.
Histologic features of an adrenal cortical adenoma. The neoplastic cellsare vacuolated because of the presence of intracytoplasmic lipid.There is mild nuclearpleomorphism. Mitotic activity and necrosis are not seen
Nodular hyperplasia of the adrenal contrasted with normal adrenalgland. In cross-section, the adrenal cortex is yellow, thickened, andmultinodular, owing to hypertrophyand hyperplasia of the lipid-rich zonae fasciculata and reticularis
MorphologyThe main lesions of Cushingsyndrome are found in the pituitaryand adrenal glands. The pituitary inCushing syndrome shows changesregardless of the cause. The mostcommon alteration, resulting fromhigh levels of endogenous orexogenous glucocorticoids, istermed Crooke hyaline change. Inthis condition, the normal granular,basophilic cytoplasm of the ACTH-producing cells in the anteriorpituitary is replaced byhomogeneous, lightly basophilicmaterial. This alteration is the resultof the accumulation of intermediatekeratin filaments in the cytoplasm.
Noteinceased levels of cortisol produce feedbackeffects on the non-tumorous corticotrophs,resulting in aggregates of intermediatecytoferatin filaments in the cytoplasm,producing the Crookes hyaline change seenmicroscopically
The morphology of the adrenal glands depends on the cause ofthe hypercortisolism. The adrenals have one of the followingabnormalities: (1) cortical atrophy; (2) diffuse hyperplasia; (3) nodularhyperplasia; and (4) an adenoma, rarely a carcinoma. In patients inwhom the syndrome results from exogenous glucocorticoids,suppression of endogenous ACTH results in bilateral cortical atrophy,due to a lack of stimulation of the zonae fasciculata and reticularis byACTH. The zona glomerulosa is of normal thickness in such cases,because this portion of the cortex functions independently of ACTH. Incases of endogenous hypercortisolism, in contrast, the adrenals eitherare hyperplastic or contain a cortical neoplasm. Diffuse hyperplasia isfound in 60% to 70% of cases of endogenous Cushing syndrome. Theadrenal cortex is diffusely thickened and yellow, as a result of anincrease in the size and number of lipid-rich cells in the zonaefasciculata and reticularis. Some degree of nodularity is common but ispronounced in nodular hyperplasia). This takes the form of bilateral,0.5- to 2.0-cm, yellow nodules scattered throughout the cortex,separated by intervening areas of widened cortex.
The combined adrenals may weigh as much as 30 to 50 gm. Thismacronodularity appears to be an extension of the diffusehyperplasia, because the cortex between the nodules exactlyresembles that found in the diffuse form of this condition. Primaryadrenocortical neoplasms causing Cushing syndrome may bemalignant or benign. The adrenocortical adenomas are yellow tumorssurrounded by thin or well-developed capsules, and most weigh lessthan 30 gm). Their morphology is identical to that of nonfunctionaladenomas and of adenomas associated with hyperaldosteronism (seebelow). Microscopically, they are composed of cells that are similar tothose encountered in the normal zona fasciculata. The carcinomasassociated with Cushing syndrome, by contrast, tend to be larger thanthe adenomas. These tumors are unencapsulated masses frequentlyexceeding 200 to 300 gm in weight, having all of the anaplasticcharacteristics of cancer, as detailed later. With both functioningbenign and malignant tumors, the adjacent adrenal cortex and that ofthe contralateral adrenal gland are atrophic because of suppression ofendogenous ACTH by high cortisol levels
Clinical featuresObesity ((centripetal distribution of adipose tissue &"buffalo hump").Moon face.Hirsutism or hypertrichosis.Immun suppression.Cutaneous striae.muscle weekness.Osteoprosis (protien catabolism &bone resorption.Hypertensionhyperglycemia. skin pigmentation.Neurological manifestation.Polycythemia and lymphopenia.
HyperaldosteronismAbout 75% of cases of primary aldosteronism are caused bysolitary adrenal adenomas (aldosteronoma). In one- quarterof cases, adrenal hyperplasia is involved. The remainderreflect bilateral hyperplasia of the adrenal zonaglomerulosa. Only a few cases of primary aldosteronism arecaused by adrenal carcinomas.In secondary hyperaldosteronism, aldosterone release occursin response to activation of the renin-angiotensin system. It ischaracterized by increased levels of plasma renin and isencountered in conditions associated with: Decreased renalperfusion (arteriolar nephrosclerosis, renal arterystenosis)Arterial hypovolemia and edema (congestive heartfailure, cirrhosis, nephrotic syndrome)Pregnancy (caused byestrogen-induced increases in plasma renin substrate)
In roughly 80% of cases, primary hyperaldosteronism is caused by an aldosterone-secreting adenoma in one adrenal gland, a condition referred to as Conn syndrome.In most cases, the adenomas are solitary, small (<2 cm in diameter), encapsulatedlesions, although multiple adenomas may be present in an occasional patient;carcinomas resulting in hyperaldosteronism are rare. In contrast to corticaladenomas associated with Cushing syndrome, those associated withhyperaldosteronism do not usually suppress ACTH secretion. Therefore, the adjacentadrenal cortex and that of the contralateral gland are not atrophic. They are brightyellow on cut section and, surprisingly, are composed of lipid-laden cortical cellsmore closely resembling fasciculata cells than glomerulosa cells (the normal sourceof aldosterone). In general, the cells tend to be uniform in size and shape;occasionally there is some nuclear and cellular pleomorphism (Fig. 20-38). Acharacteristic feature of aldesterone-producing adenomas is the presence ofeosinophilic, laminated cytoplasmic inclusions, known as spironolactone bodies.These are typically found after treatment with the anti-hypertensive drugspironolactone, which is the drug of choice in primary hyperaldosteronism. In about15% of cases, primary hyperaldosteronism is caused by bilateral primaryadrenocortical hyperplasia, characterized by bilateral nodular hyperplasia of theadrenal glands, highly reminiscent of those found in the nodular hyperplasia ofCushing syndromemorphology
The clinical manifestations of primary hyperaldosteronismare those of hypertension and hypokalemia. Serum reninlevels, as mentioned earlier, are low. Conn syndrome occursmost frequently in middle adult life and is more common infemales than in males (2 : 1). Although aldosterone-producingadenomas account for less than 1% of cases of hypertension,it is important to recognize them, because they cause asurgically correctable form of hypertension. Primary adrenalhyperplasia associated with hyperaldosteronism occurs moreoften in children and young adults than in older adults;surgical intervention is not very beneficial in these patients,and this condition is best managed with medical therapy withan aldosterone antagonist such as spironolactone. Thetreatment of secondary hyperaldosteronism rests oncorrecting the underlying cause of the stimulation of therenin-angiotensin system
Adrenogenital SyndromesExcess of androgens may be caused by a number of diseases, including primary gonadaldisorders and several primary adrenal disorders. The adrenal cortex secretes twocompounds-dehydroepiandrosterone and androstenedione-which require conversionto testosterone in peripheral tissues for their androgenic effects. Unlike gonadalandrogens, adrenal androgen formation is regulated by ACTH; thus, excessive secretioncan occur either as a "pure" syndrome or as a component of Cushing disease. Theadrenal causes of androgen excess include adrenocortical neoplasms and anuncommon group of disorders collectively designated congenital adrenal hyperplasia(CAH). Adrenocortical neoplasms associated with symptoms of androgen excess(virilization) are more likely to be carcinomas than adenomas. They aremorphologically identical to other functional or nonfunctional cortical neoplasms.CAHs represent a group of autosomal recessive disorders, each characterized by a hereditarydefect in an enzyme involved in adrenal steroid biosynthesis, particularly cortisol. In theseconditions, decreased cortisol production results in a compensatory increase in ACTH secretiondue to absence of feedback inhibition. The resultant adrenal hyperplasia causes increasedproduction of cortisol precursor steroids, which are then channeled into synthesis of androgenswith virilizing activity. Certain enzyme defects may also impair aldosterone secretion, adding saltloss to the virilizing syndrome. The most common enzymatic defect in CAH is 21-hydroxylasedeficiency, which accounts for more than 90% of cases. 21-Hydroxylase deficiency may rangefrom a total lack to a mild loss, depending on the nature of the underlying mutation involving thCYP21B gene, which encodes this enzyme
In all cases of CAH, the adrenals are hyperplastic bilaterally,sometimes expanding to 10 to 15 times their normal weights,because of the sustained elevation in ACTH. The adrenal cortex isthickened and nodular, and on cut section, the widened cortexappears brown as a result of depletion of all lipid. Theproliferating cells are mostly compact, eosinophilic, lipid-depleted cells, intermixed with lipid-laden clear cells. In additionto cortical abnormalities, adrenomedullary dysplasia has alsobeen recently reported in patients with the salt-losing 21-hydroxylase deficiency. The medullary dysplasia is characterizedby incomplete migration of the chromaffin cells to the center ofthe gland, with pronounced intermingling of nests of chromaffinand cortical cells in the periphery. Hyperplasia of corticotroph(ACTH-producing) cells is present in the anterior pituitary in mostpatientsmorphology
Clinical featuresmasculinization in females, ranging fromclitoral hypertrophy and pseudo-hermaphroditism in infantsoligomenorrhea, hirsutism, and acne inpostpubertal females.In males, androgen excess is associated withenlargement of the external genitalia andother evidence of precocious puberty inprepubertal patients and with oligospermia inolder individuals
Adrenal carcinomaAdrenocortical carcinomas are rare neoplasms that may occur at anyage, including in childhood.). Microscopically, adrenocorticalcarcinomas may be composed of well-differentiated cells resemblingthose seen in cortical adenomas or bizarre, pleomorphic cells, whichmay be difficult to distinguish from those of an undifferentiatedcarcinoma metastatic to the adrenal .Adrenal cancers have a strong tendency to invade the adrenal vein,vena cava, and lymphatics. Metastases to regional and periaorticnodes are common, as are distant hematogenous spread to the lungsand other viscera.Bone metastases are unusual. The median patient survival is about 2years.
ADRENOCORTICAL NEOPLASMSAdrenal carcinoma. The hemorrhagic and necrotic tumor dwarfs thekidney and compresses the upper pole.
Adrenal carcinoma (A) revealing marked anaplasia,contrasted with normal cortical cells (B).
Waterhouse-Friderichsen syndromeSudden withdrawal of long-termcorticosteroid therapyStress in patients with underlyingchronic adrenal insufficiencyAdrenal InsufficiencyAcuteChronic
Waterhouse-Friderichsen syndrome. At autopsy, the adrenals were grossly hemorrhagicand shrunken; microscopically, little residual cortical architecture is discernible.