The adrenal glands are located above the kidneys and are composed of the adrenal cortex and medulla. The cortex secretes mineralocorticoids like aldosterone and glucocorticoids like cortisol. It also secretes small amounts of adrenal androgens. The medulla secretes catecholamines such as epinephrine and norepinephrine in response to sympathetic stimulation. Diseases of the adrenal glands can result in either hypo- or hypersecretion of hormones with various clinical effects.

1. Adrenal gland

2. Anatomy
• There are 2 adrenal glands each weighing
about 4 gms
• They lie at the superor poles of the two
kidneys
• Each gland is composed of two distinct parts
adrenal cortex and adrenal medulla
• Blood supplied by superior ,inferior and
middle adrenal arteries

3. location

4. Section of adrenal gland

5. Adrenal cortex
Three distinct layers-
• Zona glomerulosa- thin layer under the capsule 15% of
the cortex. The cells here capable of secreting
significant amount of aldosterone
• Zona fasiculata- middle widest layer 75%of cortex
secreting glucocorticoids, cortisol and corticosterone
as well as small amount of adrenal androgens and
estrogen
• Zona reticularis- deep layer secretes adrenal
androgens dehydroepiandrosterone(DHEA) and
androstenedione as well as small amount of estrogen
and glucocorticoid

6. Adrenal medulla
• It occupies the central 20 % of the adrenal
gland
• It secretes the hormones epinephrine and nor
epinephrine in response to sympathetic
stimulation they are referred to as
catecholamines

7. Biosynthesis of adrenal steroids
• Important steroid products of adrenal cortex are
aldosterone , cortisol and androgens
• All the steps of syntheis occurs in mitochondria and
endoplasmic reticulum
• Approx 90-95% of cortisol in plasma binds to plasma
protein globulin called transcortin and to albumin
• Binding serves as a reservoir to lessen rapid
fluctuations in free hormone concentration
• Adrenal steroids are degraded mainly by liver and
conjugated to glucoronic acid or sulphates
• 25% of these conjugates are excreted in the bile and
then in feces and remaining in urine

9. Mineralocorticoid- aldosterone
• Aldosterone is the principal mineralocorticoid
secreted by the adrenal glands
• Aldosterone exerts 90% of the mineralocorticoid
activity of adrenal cortex rest 10 % is by cortisol
• Aldosterone increases the reabsorption of
sodium ions in the ECF
• It acts on principal cells of collecting ducts in the
kidney increasing sodium in exchange of
potassium and hydrogen ions

10. Mechanism of action

11. Renin angiotensin aldosterone system
(RAAS)
• Aldosteone secretion is mainly controlled by
angiotensin and potassium acting directly on
adrenocortical cells

13. Factors that play a role in regulation of
aldosterone
• Increased potassium ion concentration in the
extracellular fluid
• Increased angiotensin II concentration in ECF
• Increased sodium ion concentation in ECF
• ACTH from anterior pituitary

16. Primary aldosteronism (Conn’s
syndrome)
• A small tumor of zona glomerulosa secrete large
amount of aldosterone
• The important effects are hypokalemia, mild
metabolic alkalosis, slight increase in extracellular
fluid volume and blood volume
• There is sometimes muscle paralysis due to
hypokalemia
• There is decreased renin concentration
• Treatment include surgical removal of tumor or
treatment with antagonist of mineralocorticoid
receptor with spironolactone

17. Aldosterone cell signalling pathway

18. • activation of MR receptor can be antagonized
with Spironolactone
• Amiloride is a drug that can block sodium
reabsorption
• This is used in treatment of primary
aldosteronism

20. Glucocorticoids
• 95% of glucocorticoid activity occurs from
secretion of cortisol known as hydrocortisone
• Cortisol has effects on
– Carbohydrate metabolism
– Protein metabolism
– Fat metabolism
– Antiinfammatory effects

22. Regulation of cortisol secretion
• ACTH stimulates cortisol secretion
– Secretion of cortisol is controlled entirely by ACTH
• ACTH activates by increase in cAMP
– ACTH acts on adrenaocortical cells to activate
adeny cyclase
– Long term activation can cause hypertrophy
• Inhibitory effect of cortisol
– Cortisol sends negative feedback to hypothalamus
and pituitary to regulate cortisol levels

23. Regulation of cortisol secretion

24. Different types of stress that increase
cortisol release
• Trauma of any type
• Infection
• Intense heat or cold
• Injection of norepinephrine
• Surgery
• Any debilitating disease

25. Effect of cortisol in preventing
inflammation
• Cortisol stabilizes the lysosomal membrane
• Cortisol decreases the permeability of the
capillaries preventing loss of plasma into tissues
• Cortisol decreases migration of WBCs into
inflamed area and phagocytosis of damaged cells
• Cortisol suppresses the immune system causing
lymphocyte reproduction to decrease
• Cortisol attenuates fever as it reduces the release
of interleukin-1

26. Adrenal androgens
• Adrenal androgens mainly dehydroepisterone
is continully secreted by adrenal cortex during
fetal life
• Small amount of estrogen and progesterone
are also secreted
• It is believed early devlopment of male sex
organs result from adrenal androgens
• Alrenal androgens are also responsible for
axillary and pubic hair in females

27. Hypoadrenalism (Addison’s disease)
• This is due to insufficient adrenocortical
hormones
• Most common cause is primary atrophy or
injury, tuberculous destruction of the gland or
cancer
• Disturbances cause mineralocorticoid
deficiency, Glucocorticoid deficiency and
melanin pigmentation

28. Features of Addison’s disease

29. Addison’s disease
• Mineralocorticoid deficiency
– Results in loss of sodium ions, chloride ions and water to be lost
into urine
– This results in hyponatremia,hypercalemia and mild acidosis
– Plasma voliume falls, cardiac output and blood pressure
decreases and patient dies in shock
• Glucocorticoid deficiency
– No proper synthesis of glucose, reduced mobilization of
proteins and fats
• Melanin pigmentation
– Melanin pigmentation of mucous membrane and skin
– Melanin deposited in blothes in thin areas of the skin due to
increased sectretion of MSH

30. Addison’s disease

31. Hyperadrenalism- Cushing’s syndrome
Hypercorticolism can occur due to-
• Adenomas of the anterior pitutary secreting increased
ACTH
• Abnormal function of hypothalamus causing increased
CRH and thereby increased ACTH
• Ectopic secretion of ACTH by a tumor somewhere else
in the body
• Adenomas of the adrenal cortex
When cushing’s syndrome is secondary to excess
secretion of ACTH by the anterior pituitary this is called
Cushing’s disease

35. Adrenal medulla
• The medulla has chromaffin cells named for
characteristic brown staining with chromic acid
• Approx. 20% noradrenaline and 80% adrenaline
is secreted
• Medulla recieves input from sympathetic nervous
system through preganglionic fibres
• They end directly on modified neuronal cells that
secrete epinephrine and norepinephrine into
blood stream
• These secretory cells are embryonically derived
from nervous tissue

36. Syntheis of catecholamines

37. Degradation of catecholamines

38. Factors controlling secretion of
catecholamines
• Position of individual- standing increases
norepinephrine
• Exercise
• Hypoglycemia stronly stimulates epinephrine secretion
• Cigarette smoking
• Surgery – both epinephrine and norepinephrine
secretion
• Ketoacidosis
• Myocardial infarction
• Anesthesia

39. Adrenergic receptors
• There are 2 types of adrenergic receptors alpha
and beta receptors
• Beta receptors are type 1,2 and 3 while alpha are
type 1 and 2
• Norepinephrine and epinephrine both of which
are secreted into the blood have slightly different
effects in exciting alpha and beta receptors
• Norepinephrine exites mainly alpha receptors but
beta also to lesser extent epinephrine exites both
• Effect is determined by type of receptors in the
organs

40. Adrenergic receptors

41. Alarm or stress response of
symphathetic nervous system
• Increased arterial pressure
• Increased blood flow to active muscles for motor
activity
• Increased rate of cellular metabolism
• Increased glucose concentation
• Increased glycolysis in liver and muscles
• Increased muscle strength
• Increased mental activity
• increased rate of blood coagulation

42. Pheochromocytoma
• Tumors arise from chromaffin cells that
secrete catecholamines
• 90% tumors arise in adrenal medulla
• They are rare and equal occurance in males
and females
• If present in children it may be heriditary
• Most common feature is hypertension

44. Tests for adrenal dysfunction