1
15 13 : 1Pathology of Adrenal glandDirected by Dr/ Ali
HassanDone by : Yasmin AL-BashiriSama AL-Absi
15 13 : 2
Zona glomerulosa
Zona fasciculataZona reticularisAdrenal cortex
15 13 : 3About 15% of cortex volume---Structure:LMcells : small,
low columnar or polygonal be arranged into nests or clusters
Zona glomerulosa nuclei: deep stained, round cytoplasm: light
basophilic---Function: secrete mineralocorticoid ( e.g.
aldosterone) regulate electrolyte and water balance
15 13 : 4Zona fasciculataAbout 78% of cortex
volume---Structure:LMcells : largeclear margin be arranged in
straight cords cytoplasm: light staining(appear vacuolated
(foamy---Functionsecrete glucocorticosteroid (e.g.
cortisolcorticosterone ) and androgen (less)regulate carbohydrate,
protein and lipid metabolisminfluence immune response
15 13 : 5Zona reticularis7% of cortex
volume---Structure:LMcells: polyhedral and small; be arranged in
irregular anastomosing cords cytoplasm:
acidophilic---Function:secret androgen (testosterone) andsmall
amount of estrogen
15 13 : 6Functions of minralocortiosterols
Aldosterol regulation of water and electrolytes balace
15 13 : 7Function of gloucosteroids
15 13 : 8Function of gloucosteroids1 . Metabolic effects :
:a) Charbohydrate metabolism
Stimulation of gloucogenesis .Decrease gloucose utilization by
cells .Elevated blood gluocose concentration .
15 13 : 91 . 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
15 13 : 101 . Metabolic effects :
c)Fat metabolism :
Moblisation of fatty acids .Obisty caused by excess cortisol
.
15 13 : 112 . Premissive effects :
15 13 : 123 . Effects on water and electolytes metabolism :
15 13 : 134 . Effects on blood cells and lymphatic organs :
15 13 : 145 . Effects on nervous function :
15 13 : 156 . Resistance to stress
15 13 : 167 . Anti inflammatory :
15 13 : 178 . Anti allergic :
15 13 : 189 . Effect the respiratory system :
15 13 : 1910 . Effects other hormones :
15 13 : 20Cortisol 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
.
15 13 : 211)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
15 13 : 22Unwanted 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
15 13 : 23Functions of six hormones
15 13 : 24
The adrenal medulla
15 13 : 25
capsule: connective tissue---cortex: yellow, derived from
mesoderm---medulla: reddish-brown, derived from neural ectoderm
15 13 : 26
Adr. cellNoradr. cell
EMelectron-dense granules adrenaline cell: 80% i. heart rate ii.
dilate blood vessel
noradrenaline cell: 20% i. blood pressure ii. the flow speed of
blood
---Function: secrete adrenaline and noradrenaline secrete some
polypeptides (galanin, neuropeptide Y, enkephalin)
15 13 : 27
The adrenal medulla
15 13 : 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.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
15 13 : 29CORTEX MEDULLAMesodermal in originEctodermal in
originIt 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
15 13 : 30 2- Sympathetic Multipolar Nerve Cells: They are the
cell bodies of sym~ neurons, which probably stimulate 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 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).
15 13 : 31DISEASES OF ADRENAL GLAND
15 13 : 32Cushing 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 , whencerebrospinal fluid pressure rises to
equal the arterial pressure , it compresses the whole brain as well
as the arteries in the brain and cutsIschemic response that causes
the aterial off the blood supply to theHas risen to a level higher
pressure to rise.When the arterial pressurepressure, blood will
flow once again into than the cerebrospinal fluidthe 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 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 arteriesCushings reaction
15 13 : 33Hypersecretion by the adrenal cortex causes a
complexcascade of hormone effects called Cushings syndrome.Most of
the abnormalities of Cushings 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) ectopicThe differences between cushings disease and
cushings sydrome with its causes
15 13 : 34 secretion of ACTH by a tumor elsewhere in the body
such as an abdominal carcinoma; and (4) adenomas ofthe adrenal
cortex. When Cushings syndrome is secondaryto excess secretion of
ACTH by the anteriorpituitary, this is referred to as Cushings
disease. (5)Cushings syndrome can also occur when large amounts of
glucocorticoids are administered over prolongedperiods for
therapeutic purposes. For example,patients with chronic
inflammationsuch as rheumatoid arthritis are often treated
withglucocorticoids and may develop some of the clinicalsymptoms of
Cushings syndrome
15 13 : 35Administration of large doses of dexamethasone,a
synthetic glucocorticoid, can be used to distinguishbetween
ACTH-dependent and ACTH-independentCushings 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 Cushings syndrome.Identifying
cushings disease
15 13 : 36
15 13 : 37
15 13 : 38
15 13 : 39
15 13 : 40cortical atrophy
15 13 : 41
Adrenal cortical adenoma. The adenoma is distinguished from
nodular hyperplasia by its solitary, circumscribed nature. The
functional status of an adrenal corticaladenoma cannot be predicted
from its gross or microscopic appearance.
15 13 : 42
Cortical adenoma
15 13 : 43
Histologic features of an adrenal cortical adenoma. The
neoplastic cells are vacuolated because of the presence of
intracytoplasmic lipid. There is mild nuclearpleomorphism. Mitotic
activity and necrosis are not seen
15 13 : 44
Nodular hyperplasia of the adrenal contrasted with normal
adrenal gland. In cross-section, the adrenal cortex is yellow,
thickened, and multinodular, owing to hypertrophyand hyperplasia of
the lipid-rich zonae fasciculata and reticularis
15 13 : 45Cortical hyperplasia
15 13 : 46MorphologyThe 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.
15 13 : 47Noteinceased 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
15 13 : 48The 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.
15 13 : 49The 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
49
15 13 : 50
15 13 : 51Clinical 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.
15 13 : 52HyperaldosteronismAbout 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)
15 13 : 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 (
