It includes the histological , phsiological , pathological and histopathological charaterstics of adrenal gland.

3. About 15% of cortex volume
---Structure:
LM
small, low columnar:cells
or polygonal
be arranged into nests or clusters
Zona glomerulosa
deep stained, round:nuclei
light basophilic:cytoplasm
---Function: secrete mineralocorticoid ( e.g. aldosterone) regulate
electrolyte and water balance

4. Zona fasciculata
About 78% of cortex volume
---Structure:
LM
clear margin，large:cells
be arranged in straight cords
: light stainingcytoplasm appear vacuolated (foamy
---Function
secrete glucocorticosteroid
(e.g. cortisol、corticosterone ) and androgen (less)
regulate carbohydrate, protein and lipid metabolism
influence immune response

5. Zona reticularis
7% of cortex volume
---Structure:
LM
: polyhedral and small;cells
be arranged in irregular
anastomosing cords
acidophilic:cytoplasm
---Function:
secret androgen (testosterone) and
small amount of estrogen

6. Functions of
minralocortioster
ols
Aldosterol regulation of water and electrolytes balace

7. Function of
gloucosteroids

8. Function of gloucosteroids
1 . Metabolic effects :
a) Charbohydrate metabolism
Stimulation of gloucogenesis .
Decrease gloucose utilization by cells .
Elevated blood gluocose concentration .

9. 1 . Metabolic effects:
b)Protein metabolism:
Cotisol increases liver plasma proteins .
Increased aminoacides diminshed
transport of it in to extahepatic
enhance transport in to hepatic cells

10. 1 . Metabolic effects :
c)Fat metabolism :
Moblisation of fatty acids .
Obisty caused by excess cortisol .

11. 2 . Premissive effects :

12. 3 . Effects on water and electolytes
metabolism :

13. 4 . Effects on blood cells and
lymphatic organs :

14. 5 . Effects on nervous function :

15. 6 . Resistance to stress

16. 7 . Anti inflammatory :

17. 8 . Anti allergic :

18. 9 . Effect the respiratory system :

19. 10 . Effects other hormones :

20. Cortisol in inflammation and stress :
naw just review the inflammatory prosess
a)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 .

21. 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

22. Unwanted effects related to cortisol :
These effects occurs when it is administrated in large doses as we see in our life
Increase administration in large doses causes
atrophy of all lymphoid tissues which in turn
decrease the out put of T cells and antibodies
This lead to
fulminating infection and death

23. Functions of
six hormones

25. capsule: connective tissue
---cortex: yellow, derived
from mesoderm
---medulla: reddish-
brown, derived from
neural ectoderm

26. Adr. cell
Noradr.
cell
EM
electron-dense
granules
%80:adrenaline cell
i. heart rate
ii. dilate blood vessel
%20:celladrenalinenor
i. blood pressure
ii. the flow speed of blood
---Function:
secrete adrenaline and noradrenaline
secrete some polypeptides (galanin, neuropeptide Y, enkephalin)

28. ) MEDULLA: Completely surrounded by the cortex
Masses and branching cords of cells, surrounding
fenestrated blood capillaries
CELLS- mainly Chromaffin cells)- catecholamine-secreting cells
Few nerve cells are also found in the medulla.
1.Chromaffin
Cells: Types- epinephrine and norepinephrine secreting cells
Hard to differentiate between them in H & E preparations
Large polyhedral cells + central round vesicular nuclei
Cytoplasm-Chromaffin granules-brown color-stain-chromium
salts..
 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

29. CORTEX MEDULLA
Mesodermal in origin Ectodermal in origin
It consists of 3 zones:
glomerulosa,
fasciculata &
reticularis.
It is formed of
chromaffin cells and
nerve cells.
It secretes
mineralocorticoids,
glucocorticoids and
sex hormones.
It secretes
epinephrine &
norepinephrine.
It gives -ve
chromaffin reaction.
It gives +ve
chromaffin reaction.
It is supplied by
arterial blood.
It is supplied by
arterial and venous
blood.
It is essential for life. Not essential for life.
Differences between suprarenal cortex and medulla

30. 2- Sympathetic Multipolar Nerve Cells:
They are the cell bodies of sym~ neurons, which probably
stimulate the secretory activity of the Medullary cells
Functions 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 to
presence of epinephrine& norepinephrine.
a. Ferric chloride stains the medulla Green.
b. Iodine stains the medulla red.
c. Cramer's reaction: Exposure of suprarenal gland to osmium
vapor, stain both cortex (due to fat) and medulla black.
d. Chromaffin reaction: When fresh suprarenal gland is fixed in
chromic acid or K dichromate, medulla accepts a brown color (+ve
chromaffin reaction).

31. DISEASES OF ADRENAL GLAND

32. Cushing Reaction. The so-called Cushing reaction is a special type of
CNS ischemic response that results from increase pressure of the cere-
brospinal fluid around the brain in the cranil vault . For instance , when
cerebrospinal fluid pressure rises to equal the arterial pressure , it
compresses the whole brain as well as the arteries in the brain and cuts
Ischemic response that causes the aterialoff the blood supply to the
Has risen to a level higherpressure to rise.When the arterial pressure
pressure, blood will flow once again intothan the cerebrospinal fluid
the brain to relieve the brain ischemia.thus bloob pressure comes to
a new equilibrium level slightly higher than the cerebrospinal fluid pres.
allowing blood to begin again to flow through the brain
caused in this instance by pumping fluid under pressure
into the cranial vault around the brain. The Cushing
reaction helps protect the vital centers of the brain from
loss of nutrition if ever the cerebrospinal fluid pressure
rises high enough to compress the cerebral arteries

33. Hypersecretion by the adrenal cortex causes a complex
cascade of hormone effects called Cushing’s syndrome.
Most of the abnormalities of Cushing’s syndrome are
ascribable to abnormal amounts of cortisol, but excess
secretion of androgens may also cause important
effects. Hypercortisolism can occur from multiple
causes, including (1) adenomas of the anterior pituitary
that secrete large amounts of ACTH, which then causes
adrenal hyperplasia and excess cortisol secretion; (2)
abnormal function of the hypothalamus that causes high
levels of corticotropin-releasing hormone (CRH),
which stimulates excess ACTH release; (3) “ectopic

34. secretion” of ACTH by a tumor elsewhere in the
body such as an abdominal carcinoma; and (4)
adenomas of
the adrenal cortex. When Cushing’s syndrome is
secondary
to excess secretion of ACTH by the anterior
pituitary, this is referred to as Cushing’s disease.
(5)Cushing’s syndrome can also occur when large
amounts of glucocorticoids are administered over
prolonged
periods for therapeutic purposes. For example,
patients with chronic inflammation
such as rheumatoid arthritis are often treated with
glucocorticoids and may develop some of the clinical
symptoms of Cushing’s syndrome

35. Administration of large doses of dexamethasone,
a synthetic glucocorticoid, can be used to distinguish
between ACTH-dependent and ACTH-independent
Cushing’s syndrome. In patients who have overproduction
of ACTH due to an ACTH-secreting pituitary
adenoma or to hypothalamic-pituitary dysfunction,
even large doses of dexamethasone usually do not
suppress ACTH secretion. In contrast, patients with
primary adrenal overproduction of cortisol (ACTHindependent)
usually have low or undetectable levels of
ACTH. The dexamethasone test, although widely used,
can sometimes give an incorrect diagnosis, because
some ACTH-secreting pituitary tumors respond to
dexamethasone with suppressed ACTH secretion.
Therefore, it is usually considered to be a first step in
the differential diagnosis of Cushing’s syndrome.

40. cortical atrophy

41. Adrenal cortical adenoma. The adenoma is distinguished from nodular
hyperplasia by its solitary, circumscribed nature. The functional status of an adrenal
cortical
adenoma cannot be predicted from its gross or microscopic appearance.

42. Cortical adenoma

43. Histologic features of an adrenal cortical adenoma. The neoplastic cells
are vacuolated because of the presence of intracytoplasmic lipid.
There is mild nuclear
pleomorphism. Mitotic activity and necrosis are not seen

44. Nodular hyperplasia of the adrenal contrasted with normal adrenal
gland. In cross-section, the adrenal cortex is yellow, thickened, and
multinodular, owing to hypertrophy
and hyperplasia of the lipid-rich zonae fasciculata and reticularis

45. Cortical hyperplasia

46. Morphology
The main lesions of Cushing
syndrome are found in the pituitary
and adrenal glands. The pituitary in
Cushing syndrome shows changes
regardless of the cause. The most
common alteration, resulting from
high levels of endogenous or
exogenous glucocorticoids, is
termed Crooke hyaline change. In
this condition, the normal granular,
basophilic cytoplasm of the ACTH-
producing cells in the anterior
pituitary is replaced by
homogeneous, lightly basophilic
material. This alteration is the result
of the accumulation of intermediate
keratin filaments in the cytoplasm.

47. Note
inceased levels of cortisol produce feedback
effects on the non-tumorous corticotrophs,
resulting in aggregates of intermediate
cytoferatin filaments in the cytoplasm,
producing the Crooke's hyaline change seen
microscopically

48. The morphology of the adrenal glands depends on the cause of
the hypercortisolism. The adrenals have one of the following
abnormalities: (1) cortical atrophy; (2) diffuse hyperplasia; (3) nodular
hyperplasia; and (4) an adenoma, rarely a carcinoma. In patients in
whom 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 by
ACTH. The zona glomerulosa is of normal thickness in such cases,
because this portion of the cortex functions independently of ACTH. In
cases of endogenous hypercortisolism, in contrast, the adrenals either
are hyperplastic or contain a cortical neoplasm. Diffuse hyperplasia is
found in 60% to 70% of cases of endogenous Cushing syndrome. The
adrenal cortex is diffusely thickened and yellow, as a result of an
increase in the size and number of lipid-rich cells in the zonae
fasciculata and reticularis. Some degree of nodularity is common but is
pronounced 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.

49. The combined adrenals may weigh as much as 30 to 50 gm. This
macronodularity appears to be an extension of the diffuse
hyperplasia, because the cortex between the nodules exactly
resembles that found in the diffuse form of this condition. Primary
adrenocortical neoplasms causing Cushing syndrome may be
malignant or benign. The adrenocortical adenomas are yellow tumors
surrounded by thin or well-developed capsules, and most weigh less
than 30 gm). Their morphology is identical to that of nonfunctional
adenomas and of adenomas associated with hyperaldosteronism (see
below). Microscopically, they are composed of cells that are similar to
those encountered in the normal zona fasciculata. The carcinomas
associated with Cushing syndrome, by contrast, tend to be larger than
the adenomas. These tumors are unencapsulated masses frequently
exceeding 200 to 300 gm in weight, having all of the anaplastic
characteristics of cancer, as detailed later. With both functioning
benign and malignant tumors, the adjacent adrenal cortex and that of
the contralateral adrenal gland are atrophic because of suppression of
endogenous ACTH by high cortisol levels

51. Clinical features
Obesity ((centripetal distribution of adipose tissue &"buffalo hump").
Moon face.
Hirsutism or hypertrichosis.
Immun suppression.
Cutaneous striae.
muscle weekness.
Osteoprosis (protien catabolism &bone resorption.
Hypertension
hyperglycemia.
 skin pigmentation.
Neurological manifestation.
Polycythemia and lymphopenia.

52. Hyperaldosteronism
About 75% of cases of primary aldosteronism are caused by
solitary adrenal adenomas (aldosteronoma). In one- quarter
of cases, adrenal hyperplasia is involved. The remainder
reflect bilateral hyperplasia of the adrenal zona
glomerulosa. Only a few cases of primary aldosteronism are
caused by adrenal carcinomas.
In secondary hyperaldosteronism, aldosterone release occurs
in response to activation of the renin-angiotensin system. It is
characterized by increased levels of plasma renin and is
encountered in conditions associated with: Decreased renal
perfusion (arteriolar nephrosclerosis, renal artery
stenosis)Arterial hypovolemia and edema (congestive heart
failure, cirrhosis, nephrotic syndrome)Pregnancy (caused by
estrogen-induced increases in plasma renin substrate)

53. 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), encapsulated
lesions, although multiple adenomas may be present in an occasional patient;
carcinomas resulting in hyperaldosteronism are rare. In contrast to cortical
adenomas associated with Cushing syndrome, those associated with
hyperaldosteronism do not usually suppress ACTH secretion. Therefore, the adjacent
adrenal cortex and that of the contralateral gland are not atrophic. They are bright
yellow on cut section and, surprisingly, are composed of lipid-laden cortical cells
more closely resembling fasciculata cells than glomerulosa cells (the normal source
of aldosterone). In general, the cells tend to be uniform in size and shape;
occasionally there is some nuclear and cellular pleomorphism (Fig. 20-38). A
characteristic feature of aldesterone-producing adenomas is the presence of
eosinophilic, laminated cytoplasmic inclusions, known as spironolactone bodies.
These are typically found after treatment with the anti-hypertensive drug
spironolactone, which is the drug of choice in primary hyperaldosteronism. In about
15% of cases, primary hyperaldosteronism is caused by bilateral primary
adrenocortical hyperplasia, characterized by bilateral nodular hyperplasia of the
adrenal glands, highly reminiscent of those found in the nodular hyperplasia of
Cushing syndrome
morphology

54. Con’s disease

55. spironolactone bodies

56. The clinical manifestations of primary hyperaldosteronism
are those of hypertension and hypokalemia. Serum renin
levels, as mentioned earlier, are low. Conn syndrome occurs
most frequently in middle adult life and is more common in
females than in males (2 : 1). Although aldosterone-producing
adenomas account for less than 1% of cases of hypertension,
it is important to recognize them, because they cause a
surgically correctable form of hypertension. Primary adrenal
hyperplasia associated with hyperaldosteronism occurs more
often 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 with
an aldosterone antagonist such as spironolactone. The
treatment of secondary hyperaldosteronism rests on
correcting the underlying cause of the stimulation of the
renin-angiotensin system

57. Adrenogenital Syndromes
Excess of androgens may be caused by a number of diseases, including primary gonadal
disorders and several primary adrenal disorders. The adrenal cortex secretes two
compounds-dehydroepiandrosterone and androstenedione-which require conversion
to testosterone in peripheral tissues for their androgenic effects. Unlike gonadal
androgens, adrenal androgen formation is regulated by ACTH; thus, excessive secretion
can occur either as a "pure" syndrome or as a component of Cushing disease. The
adrenal causes of androgen excess include adrenocortical neoplasms and an
uncommon 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 are
morphologically identical to other functional or nonfunctional cortical neoplasms.
CAHs represent a group of autosomal recessive disorders, each characterized by a hereditary
defect in an enzyme involved in adrenal steroid biosynthesis, particularly cortisol. In these
conditions, decreased cortisol production results in a compensatory increase in ACTH secretion
due to absence of feedback inhibition. The resultant adrenal hyperplasia causes increased
production of cortisol precursor steroids, which are then channeled into synthesis of androgens
with virilizing activity. Certain enzyme defects may also impair aldosterone secretion, adding salt
loss to the virilizing syndrome. The most common enzymatic defect in CAH is 21-hydroxylase
deficiency, which accounts for more than 90% of cases. 21-Hydroxylase deficiency may range
from a total lack to a mild loss, depending on the nature of the underlying mutation involving th
CYP21B gene, which encodes this enzyme

58. Cholesterol
Pregnenolone
Progesterone
11-Deoxycorticosterone
Corticosterone
Aldosterone(C21)
17-HYDROXYLASE
P450c17
21-HYDROXYLASE
11-HYDROXYLASE
Aldosterone synthase
17-hydroxyprogestrone
11-desoxycortisol
cortisol
cortisone
androstenedione
estrone estradiol

59. 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 is
thickened and nodular, and on cut section, the widened cortex
appears brown as a result of depletion of all lipid. The
proliferating cells are mostly compact, eosinophilic, lipid-
depleted cells, intermixed with lipid-laden clear cells. In addition
to cortical abnormalities, adrenomedullary dysplasia has also
been recently reported in patients with the salt-losing 21-
hydroxylase deficiency. The medullary dysplasia is characterized
by incomplete migration of the chromaffin cells to the center of
the gland, with pronounced intermingling of nests of chromaffin
and cortical cells in the periphery. Hyperplasia of corticotroph
(ACTH-producing) cells is present in the anterior pituitary in most
patients
morphology

60. Clinical features
masculinization in females, ranging from
clitoral hypertrophy and pseudo-
hermaphroditism in infants
oligomenorrhea, hirsutism, and acne in
postpubertal females.
In males, androgen excess is associated with
enlargement of the external genitalia and
other evidence of precocious puberty in
prepubertal patients and with oligospermia in
older individuals

61. Adrenal carcinoma
Adrenocortical carcinomas are rare neoplasms that may occur at any
age, including in childhood.). Microscopically, adrenocortical
carcinomas may be composed of well-differentiated cells resembling
those seen in cortical adenomas or bizarre, pleomorphic cells, which
may be difficult to distinguish from those of an undifferentiated
carcinoma metastatic to the adrenal .
Adrenal cancers have a strong tendency to invade the adrenal vein,
vena cava, and lymphatics. Metastases to regional and periaortic
nodes are common, as are distant hematogenous spread to the lungs
and other viscera.
Bone metastases are unusual. The median patient survival is about 2
years.

62. ADRENOCORTICAL NEOPLASMS
Adrenal carcinoma. The hemorrhagic and necrotic tumor dwarfs the
kidney and compresses the upper pole.

63. Adrenal carcinoma (A) revealing marked anaplasia,
contrasted with normal cortical cells (B).

64. Waterhouse-Friderichsen syndrome
Sudden withdrawal of long-term
corticosteroid therapy
Stress in patients with underlying
chronic adrenal insufficiency
Adrenal Insufficiency
Acute
Chronic

65. Waterhouse-Friderichsen syndrome. At autopsy, the adrenals were grossly hemorrhagic
and shrunken; microscopically, little residual cortical architecture is discernible.