1. ADRENAL GLANDS
Najam-us-sahar
Riphah Internatiopnal University,
Pakistan

2. ADRENAL GLANDS
 Two adrenal glands
 Each weighs 4 grams
 Lie at the superior poles of the two kidneys
 Two distinct parts, adrenal medulla and adrenal cortex
 Adrenal medulla, central 20 % of the gland, is functionally
related to the SNS
 It secretes epinephrine and norepinephrine in response to
sympathetic stimulation
 Adrenal cortex secretes corticosteroids.

3. ADRENAL GLANDS

4. ADRENOCORTICAL HORMONES

5. CORTICOSTEROIDS
 Adrenocortical hormones:
 Mineralocorticoids
 Glucocorticoids
 Androgens (small amounts)
 Mineralocorticoids: affect electrolytes (“minerals”) of
extracellular fluids -sodium and potassium, in particular
 Glucocorticoids : important effects that increase blood
glucose concentration + additional effects on protein and fat
metabolism
 More than 30 steroids have been isolated from the adrenal
cortex
 Aldosterone principal mineralocorticoid
 Cortisol principal glucocorticoid.

7. ADRENAL CORTEX
 Three Distinct Layers
1. Zona glomerulosa, 15% of the adrenal cortex
 A thin layer of cells that lies just underneath the capsule
 Secrete aldosterone
 Secretion is controlled by ECF concentrations of
angiotensin II and potassium, which stimulate aldosterone
secretion.
2. Zona fasciculata, 75% of the adrenal cortex
 Middle and widest layer
 Secretes glucocorticoids cortisol, corticosterone, and
small amounts of adrenal androgens and estrogens.
 Secretion is controlled by the hypothalamic-pituitary axis
via adrenocorticotropic hormone (ACTH).

8.  Zona reticularis, deep layer of cortex
 Secretes adrenal androgens, dehydroepiandrosterone
(DHEA) and androstenedione, small amounts of estrogens
and glucocorticoids.
 ACTH regulates secretion of these cells
 Cortical androgen-stimulating hormone, released from the
pituitary, may also be involved.

9. Adrenal Gland

10. ADRENOCORTICAL HORMONES ARE STEROIDS
 Derived from Cholesterol
 Cholesterol is provided by LDL in the circulating plasma.
 Transport of cholesterol is regulated by feedback mechanisms
 For example, ACTH increases the number of adrenocortical
cell receptors for LDL, as well as the activity of enzymes that
liberate cholesterol from LDL.
 Cholesterol enters cell, delivered to mitochondria, cleaved by
enzyme cholesterol desmolase to form pregnenolone
 This initial step in steroid synthesis is stimulated by the
different factors that control secretion of the major hormone

11. SYNTHESIS OF ADRENAL STEROIDS
 Synthesis occur in two of the organelles of
the cell, mitochondria and endoplasmic
reticulum
 Each step is catalyzed by a specific enzyme
system.

13. MINERALOCORTICOIDS
1. Aldosterone (very potent, accounts for about 90 per
cent of all mineralocorticoid activity)
2. Desoxycorticosterone
3. Corticosterone
4. 9a-Fluorocortisol (synthetic)
5. Cortisol (very slight mineralocorticoid activity)
6. Cortisone (synthetic)

14. GLUCOCORTICOIDS
1. Cortisol (very potent, accounts for about 95
percent of all glucocorticoid activity)
2. Corticosterone
3. Cortisone (synthetic)
4. Prednisone (synthetic)
5. Methylprednisone (synthetic)
6. Dexamethasone (synthetic)

15. FUNCTIONS OF THE
MINERALOCORTICOIDS-ALDOSTERONE

16. MINERALOCORTICOID DEFICIENCY
 Causes Severe Renal Sodium Chloride Wasting and
Hyperkalemia.
 Total loss of adrenocortical secretion death within 3
days to 2 weeks unless the person receives extensive salt
therapy or injection of mineralocorticoids.
 Without mineralocorticoids:
 Potassium ion concentration of ECF rises
 Sodium and chloride are rapidly lost from the body
 Total ECF volume and blood volume greatly reduced
 Develops diminished cardiac output
 Progresses to a shock like state
 Followed by death
 Mineralocorticoids are said to be the acute “lifesaving” portion
of the adrenocortical hormones.

17. RENAL AND CIRCULATORY EFFECTS
 Increases Renal Tubular Reabsorption of Sodium and
Secretion of Potassium
 From renal tubular epithelial cells especially in the principal
cells of the collecting tubules and, to a lesser extent, in the
distal tubules and collecting ducts.
 Aldosterone causes sodium to be conserved in the ECF while
increasing potassium excretion in the urine.

18.  Excess Aldosterone Increases ECF Volume and
Arterial Pressure but Has Only a Small Effect on
Plasma Sodium Concentration
 Concentration of sodium in the ECF rises only a few
milliequivalents, when sodium is reabsorbed by the
tubules, there is simultaneous osmotic absorption of almost
equivalent amounts of water.
 ECF volume increases almost as much as the retained
sodium, but without much change in sodium concentration.
 Aldosterone-mediated increase in ECF volume lasting
more than 1 to 2 days also leads to an increase in arterial
pressure
 The rise in arterial pressure then increases kidney
excretion of both salt and water, called pressure natriuresis
and pressure diuresis
 This return to normal of salt and water excretion by the
kidneys is called aldosterone escape

19.  When aldosterone secretion becomes zero, large amounts
of salt are lost in the urine, not only diminishing the amount
of sodium chloride in the extracellular fluid but also
decreasing the ECF volume.
 The result is severe ECF dehydration and low blood
volume, leading to circulatory shock.
 Without therapy, this usually causes death within a few days
after the adrenal glands suddenly stop secreting
aldosterone.

20. EXCESS ALDOSTERONE CAUSES HYPOKALEMIA AND
MUSCLE WEAKNESS
 Excess aldosterone causes loss of potassium ions from the
ECF into the urine and also stimulates transport of potassium
from ECF into most cells of the body.
 Excessive secretion of aldosterone, may cause a serious
decrease in the plasma potassium concentration, This
condition is called hypokalemia.
 When the potassium ion concentration falls below about one-
half normal, severe muscle weakness often develops.

21. TOO LITTLE ALDOSTERONE CAUSES HYPERKALEMIA
AND CARDIAC TOXICITY
 When aldosterone is deficient, ECF potassium ion
concentration can rise far above normal.
 When it rises to 60 to 100 per cent above normal,
serious cardiac toxicity, including weakness of heart
contraction and development of arrhythmia becomes
evident
 Progressively higher concentrations of potassium lead
inevitably to heart failure.

22. EXCESS ALDOSTERONE INCREASES TUBULAR HYDROGEN
ION SECRETION, CAUSES MILD ALKALOSIS
 Also causes secretion of hydrogen ions in exchange for
sodium in the intercalated cells of the cortical collecting
tubules.
 This decreases the hydrogen ion concentration in the
extracellular fluid, causing a mild degree of alkalosis.

23. SWEAT GLANDS, SALIVARY GLANDS, AND
INTESTINAL EPITHELIAL CELLS
 Aldosterone Stimulates Sodium and Potassium Transport
 These glands form a primary secretion that contains large
quantities of sodium chloride, but most of it is reabsorbed,
whereas potassium and bicarbonate ions are secreted.
 Aldosterone greatly increases the reabsorption of sodium
chloride and the secretion of potassium by the ducts.
 This effect is used to conserve body salt in hot environments
 The effect on the salivary glands is necessary to conserve
salt when excessive quantities of saliva are lost.
 Aldosterone also greatly enhances sodium absorption by the
intestines, especially in the colon, which prevents loss of
sodium in the stools.

24. REGULATION OF ALDOSTERONE SECRETION
1. Increased potassium ion concentration in the
extracellular fluid greatly increases aldosterone
secretion.
2. Increased activity of the renin-angiotensin system
(increased levels of angiotensin II) also greatly
increases aldosterone secretion.
3. Increased sodium ion concentration in the extracellular
fluid very slightly decreases aldosterone secretion.
4. ACTH from the anterior pituitary gland is necessary for
aldosterone secretion but has little effect in controlling
the rate of secretion.

25. FUNCTIONS OF THE GLUCOCORTICOIDS

26.  Cortisol Is the Primary Glucocorticoid Secreted by the
Adrenal Cortex
 More than 95% of glucocorticoid activity exerted by the
adrenocortical hormones can be attributed to cortisol
known also as hydrocortisone
 Most of the remaining glucocorticoid activity is due to
corticosterone.
 Cortisol mediates most of its effects by binding with
intracellular receptors in target tissues and inducing or
repressing gene transcription
 This results in alterations in the synthesis of enzymes
that alter cell function.

27. EFFECTS OF CORTISOL ON CARBOHYDRATE METABOLISM
 Stimulation of Gluconeogenesis.
 Formation of carbohydrate from proteins and some other
substances by the liver
 Decreased Glucose Utilization by Cells
 Elevated Blood Glucose Concentration and “Adrenal
Diabetes.”
 The rise in blood glucose in turn stimulates secretion of
insulin.
 High levels of glucocorticoid reduce the sensitivity of many
tissues to the stimulatory effects of insulin on glucose
uptake and utilization.

28. EFFECTS ON PROTEIN METABOLISM
 Reduction in Cellular Protein.
 Reduction of the protein stores in essentially all body cells
except those of the liver.
 protein synthesis catabolism of protein in the cells.
 amino acid transport into extra hepatic tissues
 Enhance amino acid in plasma and increased transport
into liver cells
 Cortisol Increases Liver and Plasma Proteins.
 Increased conversion of amino acids to glucose-that is,
enhanced gluconeogenesis

29. EFFECTS ON FAT METABOLISM
 Mobilization of Fatty Acids from adipose tissue
 Increases concentration of free fatty acids in the plasma,
increases their utilization for energy.
 Cortisol also enhance the oxidation of fatty acids in cells.
 Obesity Caused by Excess Cortisol
 A peculiar type of obesity, with excess deposition of fat in
the chest and head regions of the body, giving a buffalo-
like torso and a rounded “moon face.”
 Results from excess stimulation of food intake, with fat
being generated in some tissues of the body more rapidly
than it is mobilized and oxidized.

30.  Any type of physical or mental stress causes an immediate
and marked increase in ACTH secretion by the pituitary
gland, followed by greatly increased adrenocortical
secretion of cortisol
CORTISOL IN RESISTING STRESS AND INflAMMATION

31. ANTI-INflAMMATORY EFFECTS OF CORTISOL
 Large amounts of cortisol have two basic antiinflammatory
effects:
1. It can block early stages of inflammation process before it
even begins
2. If inflammation has already begun, it causes rapid
resolution of the inflammation and increased rapidity of
healing

32. OTHER EFFECTS OF CORTISOL
 Blocks Inflammatory Response to Allergic Reactions
 Cortisol effectively prevents shock or death in anaphylaxis,
which otherwise kills many people
 Effect on Blood Cells and on Immunity in Infectious
Diseases
 Large amount of Cortisol decreases the number of
eosinophils and lymphocytes in the blood
 Large doses also causes atrophy of lymphoid tissue, which
decreases the output of T cells and antibodies
 The level of immunity for foreign invaders is decreased
 Leads to increased infection and death from diseases
 Useful drugs in preventing immunological rejection of
transplanted hearts, kidneys, and other tissues.
 Cortisol increases the production of red blood cells

33. REGULATION OF CORTISOL SECRETION

34. GLUCOCORTICOID ACTION

35. ADRENAL ANDROGENS
 The adrenal androgens DHEA and androstenedione are
secreted in appreciable amounts, but they have only weak
androgenic effects.
 Consequently, the normal plasma concentrations of these
hormones exert little effect on secondary sex
characteristics
 In females, adrenal androgens are responsible for pubic
and axillary hair.
 In males Most of the androgenic activity of adrenal
hormones may be due to the conversion of adrenal
androgens to testosterone in peripheral tissues
 The secretion of adrenal androgens is stimulated by ACTH.

36. ABNORMALITIES OF ADRENOCORTICAL
SECRETION

37. HYPOADRENALISM-ADDISON’S DISEASE
 Failure of the adrenal cortices to produce adrenocortical
hormones
 Most frequently caused by primary atrophy of the adrenal
cortices, caused by autoimmunity against the cortices.
 Also caused by tuberculous destruction of the adrenal
glands or invasion of the adrenal cortices by cancer.
 These processes usually are gradual, leading to a
progressive reduction in glucocorticoid and
mineralocorticoid function.
 As a result of the decreased cortisol secretion, there is a
compensatory increase in ACTH secretion, which produces
hyperpigmentation.

38.  Mineralocorticoid Deficiency
 Excessive loss of sodium, hypovolemia, hypotension, and
increased plasma renin activity
 Excessive potassium retention and hyperkalemia
 Mild acidosis
 Glucocorticoid Deficiency
 Abnormal carbohydrate, fat, and protein metabolism
resulting in muscle weakness, fasting hypoglycemia, and
impaired utilization of fats for energy
 Loss of appetite and weight loss
 Poor tolerance to stress.
 The inability to secrete increased amounts of cortisol
during stress leads to an Addisonian crisis that may
culminate in death if supplemental doses of adrenocortical
hormones are not administered.

39.  Treatment
 An untreated person with total adrenal destruction dies
within a few days to a few weeks because of weakness
and usually circulatory shock.
 Such a person can live for years if small quantities of
mineralocorticoids and glucocorticoids are administered
daily.

40. HYPERADRENALISM-CUSHING’S SYNDROME
 Hypersecretion by the adrenal cortex causes a complex
cascade of hormone effects called Cushing’s syndrome.
 Hypercortisolism can occur from multiple causes:
1) adenomas of the anterior pituitary ACTH
adrenal hyperplasia cortisol secretion
2) abnormal function of the hypothalamus CRH
ACTH release
3) “ectopic secretion” of ACTH by a tumor in the body
4) adenomas of the adrenal cortex
5) by administration of large amounts of exogenous
glucocorticoids.
 When Cushing’s syndrome is secondary to excess
secretion of ACTH by the anterior pituitary, this is referred
to as Cushing’s disease.

41.  Symptoms:
 Mobilization of fat from the extremities to the abdomen, face,
and supraclavicular areas
 Protein depletion resulting in muscle weakness, loss of
connective tissue and thinning of the skin (leading to purple
striae), and impaired growth in children
 Osteoporosis and vertebral fractures
 Impaired response to infections resulting from a suppressed
immune system
 Impaired carbohydrate metabolism, hyperglycemia, and
even insulin-resistant diabetes mellitus
 Masculinizing effects when adrenal androgens are secreted
in excess

42.  Treatment
 Remove an adrenal tumor
 Hypertrophied pituitary glands can be surgically removed or
destroyed by radiation.
 Drugs that block steroidogenesis, such as metyrapone,
ketoconazole, and aminoglutethimide, or that inhibit ACTH
secretion can also be used.
 If ACTH secretion cannot easily be decreased, the only
satisfactory treatment is usually bilateral partial (or even
total) adrenalectomy, followed by administration of adrenal
steroids to make up for any insufficiency that develops.

43. ADRENAL MEDULLA - HORMONES

44. FUNCTION OF THE ADRENAL MEDULLAE
 Stimulation of the sympathetic nerves to the adrenal
medulla causes large quantities of epinephrine and
norepinephrine to be released into the circulating blood.
 About 80% of the secretion from the adrenal medulla is
epinephrine, and about 20% is norepinephrine.
 The effect of the epinephrine and norepinephrine released
from the adrenal medulla lasts 5 to 10 times longer than
when they are released by sympathetic neurons because
these hormones are slowly removed from the blood.

45. ADRENERGIC RECEPTORS
 Alpha and Beta Receptors
 Norepinephrine excites mainly alpha receptors but
excites the beta receptors to a lesser extent as well.
 Conversely, epinephrine excites both types of
receptors approximately equally.
 Therefore, the relative effects of norepinephrine
and epinephrine on different effector organs are
determined by the types of receptors in the organs.

46. ALPHA AND BETA RECEPTORS
 The stimulation of α-receptors results in vasoconstriction,
dilation of the iris, contraction of the intestinal and bladder
sphincters, and contraction of the pilomotor muscles.
 The β-receptor is subdivided into β1-, β2-, and β3
receptor subtypes.
 Stimulation of β1-receptors causes an increase in heart
rate and strength of contraction.
 Stimulation of β2-receptors causes skeletal muscle
vasodilation, bronchodilation, uterine relaxation,
calorigenesis, and glycogenolysis.
 Stimulation of β3-receptors induces lipolysis in adipose
tissue and the conversion of energy in lipids into heat
(thermogenesis).

47. NOREPINEPHRINE
 The circulating Norepinephrine causes:
 Vasoconstriction
 Increased heart rate and contractility
 Inhibition of the gastrointestinal tract
 Dilated pupils.

48. EPINEPHRINE
 Epinephrine causes almost the same effects as those
caused by norepinephrine, except
 The circulating epinephrine has a greater effect on
cardiac performance
 Epinephrine causes only weak constriction of the blood
vessels in muscles
 Slight increase in arterial pressure
 A dramatic increase in cardiac output.
 The metabolic rate of every cell of the body is increased
by these hormones, especially by epinephrine, as much
as 100 per cent above normal

49.  Epinephrine and norepinephrine are almost always
released by the adrenal medullae at the same time that
the different organs are stimulated directly by
generalized sympathetic activation.
 Therefore, the organs are actually stimulated in two
ways: directly by the sympathetic nerves and indirectly
by the adrenal medullary hormones.
 The two means of stimulation support each other, and
either can, in most instances, substitute for the other.

50. Tyrosine
L-Dopa
Dopamine
hydroxylation
Norepinephrine
decarboxylation
hydroxylation
Epinephrine
Adrenal Glands
Synthesis