Lect. 5 - Adrenal glands

Question 1

Describe the Anatomy of the adrenal glands

Answer 1

An adrenal gland is actually two glands,
cortex and medulla that sit upon each
kidney.

The blood supply enters the cortex in
the subcapsular region and flows
through anastomotic capillary beds while
coursing through first the cortex and
then the medulla.

Question 2

The adrenal cortex comprises three
layers that surround the medulla:

Answer 2

zona

• Glomerulosa
• Fasciculata
• Reticularis

Question 3

The adrenal medulla contains?
Is derived from?

Answer 3

chromaffin cells.

of neuroectodermal origin

Question 4

The adrenal cortex is derived from?

Answer 4

mesoderm

Question 5

The hormone groups produced by the adrenal cortex (3):

Answer 5

glucocorticoids
mineralcorticoids
androgens

Question 6

Glucocorticoids are defined on the basis of

Answer 6

the actions they exert on gluconeogensis but are known to exert numerous other effects too.

Question 7

Name 2 glucocorticoids.

Answer 7

• cortisol (hydrocortisone as drug), controls the body’s use of fats, proteins, and carbohydrates.
• corticosterone - together with cortisol (hydrocortisone), suppresses inflammatory
  reactions in the body and also affects the immune system.

Question 8

Cortisol (hydrocortisone as drug), controls

Answer 8

the body’s use of fats, proteins, and
carbohydrates.

Question 9

Corticosterone - together with cortisol (hydrocortisone), suppresses

Answer 9

inflammatory reactions in the body and also affects the immune system.

Question 10

Name the classic mineralcorticoid and its function.

Answer 10

electrolyte metabolism e.g. aldosterone.

Inhibits the level of sodium excreted into the urine, maintaining blood volume and blood pressure.

Question 11

What is Androstenedione?

Answer 11

Androstenedione is a precursor of testosterone and other androgens, as well as of estrogens like estrone, in the body. Is producedin teh adrenal cortex.

Question 12

What is DHEA?

Answer 12

Dehydroepiandrosterone is an endogenous steroid hormone precursor produced in the adrenal cortex.

Question 13

Adrenocortical hormones are classified as either

Answer 13

mineralcorticoid or glucocorticoid in their activity, but there is an overlap in their activity.

For example, whereas cortisol is the dominant glucocorticoid hormone, it also has mineralocorticoid effects, although at reduced potency.

Question 14

The synthesis of all steroid hormones utilizes (2)

Answer 14

cholesterol and pregnenolone in the synthetic pathway.

Conversion of pregnenolone to
particular steroid hormones
depends on which steroidogenic
enzymes are present within a given
cell.

Question 15

If the synthesis of cortisol is prevented by any one of several dysfunctional enzymes, what might occur?

Answer 15

other steroid products might be produced in excess.

For example, a block in 21α-hydroxylase will iminish
production of both cortisol and aldosterone and
increase production of the sex steroids.

Question 16

Are steroid hormones stored or released?

Answer 16

Being lipid molecules, steroids are not stored within the cells once synthesized. All steroid hormones synthesized in response to a particular stimulus are released into the circulation by diffusion.

This is in marked contrast to peptide/protein hormones which are packaged within secretory granules during synthesis and are released via exocytosis.

Question 17

Describe steroid hormone transport

Answer 17

Being lipid molecules, Steroid hormones depend on binding plasma proteins for transport in blood .

Question 18

Clearence half-life of
cortisol?
aldosterone?

Answer 18

• cortisol: 60 min
• Aldosterone: 20 min

The differences are attributable to protein binding in plasma.

Metabolized in liver.

Question 19

CRH

Answer 19

Corticotropin-releasing hormone

Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis (HPA axis).

Question 20

HPA axis

Answer 20

Hypothalamic-pituitary-adrenocortical axis.

hypothalamus produces Corticotropin-releasing hormone (CRH) which stimulates the adenohypophysis to synthesize and release adrenocorticotropic hormone (ACTH) which in turn stimulates production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively.

Question 21

Cortisol exerts negative feedback at the level of

Answer 21

both the pituitary and hypothalamus.

In addition, ACTH produced by the corticotrophs negatively feeds back on the hypothalamic neurons in a “short loop.”

Question 22

Although classified as a glucocorticoid, cortisol affects

Answer 22

more than the principal glucose-regulatory
tissues, namely, the liver, fat, and muscle.

Most body tissues, including bone,
skin, other viscera, hematopoietic
and lymphoid tissue, and the central
nervous system (CNS), are target sites
for glucocorticoid action.

Question 23

Although cortisol is the primary glucocorticoid in humans, in other species (e.g., the rat), what
is the major glucocorticoid?

Answer 23

corticosterone is the major glucocorticoid in some other species.

Question 24

Main Function of Glucocorticoids

Answer 24

glucose metabolism modulation

stimulation of hepatic gluconeogenesis, which
involves the conversion of amino acids to carbohydrates.

The net result is an increase in hepatic glycogen and a tendency toward increased blood glucose levels; = insulin resistance (effect is opposite to insulin).

Question 25

Explain the anti insulin effect of glucocorticoids.

Answer 25

Glucocorticoids and insulin have similar effects on liver glycogen metabolism (stimulate gluconeogenesis), but their effects on peripherial use of glucose are different. Glucocorticoids inhibit glucose uptake by cells and glucose metabolism in peripherial tissues, particularly in muscle and adipose cells. This is the anti insulin effect. The chronic administration of glucocorticoids can lead to development of a syndrome called “steroid diabetes” because of the hyperglycemic effect produced at the level of the liver; use of glucose decreases in the peripheral tissues because of insulin antagonism.

Question 26

Metabolic Effects of Glucocorticoids on fat metabolism

Answer 26

the direct effect on adipose tissue is to increase the rate of lipolysis and to distribute fat into the liver and abdomen (“potbellied” appearance).

Question 27

Metabolic Effects of Glucocorticoids on protein metabolism

Answer 27

protein synthesis is inhibited; protein catabolism is enhanced with an accompanying release of amino acids leading to muscular atrophy. Two tissues; cardiac and brain, are spared from the effects of glucocorticoids on protein catabolism.

Question 28

Metabolic Effects of Glucocorticoids on Calcium metabolism (3)

Answer 28

negative Ca2+ balance, inhibition of ossification, osteoporosis

Question 29

Metabolic Effects of Glucocorticoids on Longitudinal growth

Answer 29

slowdown of longitudinal growth

Question 30

Metabolic Effects of Glucocorticoids on Water diuresis

Answer 30

whereas glucocorticoids inhibit vasopressin activity in the distal tubule, the most important effect is to decrease GFR.

Question 31

Metabolic Effects of Glucocorticoids on the Cardiovascular system

Answer 31

increases the sensitivity of arterial vessels to catecholamines

Question 32

Metabolic Effects of Glucocorticoids on the Immune system

Answer 32

suppresses immune system (macrophages, lymphocytes) Blocks inflammatory response

Question 33

One of the most important clinical uses of glucocorticoids is

Answer 33

the suppression of the inflammatory response

Question 34

glucocorticoids suppress the inflammatory response by

Answer 34

inhibiting the synthesis of inflammatory mediators, such as prostaglandins, thromboxanes, and leukotrienes, that rise as a result of arachidonic acid metabolism.

Question 35

Spontaneously occurring hyperadrenocorticism may be associated with (2)

Answer 35

* inappropriate secretion of ACTH by the pituitary (pituitary-dependent hyperadrenocorticism) * or associated with a primary adrenal disorder (adrenal-dependent hyperadrenocorticism)

Question 36

pituitary-dependent hyperadrenocorticism refers to

Answer 36

inappropriate secretion of ACTH by the pituitary causing hypersecretion of cortisol/Cushing's disease

Question 37

adrenal-dependent hyperadrenocorticism rfers to

Answer 37

associated with a primary adrenal gland disorder; atrophy, destruction, neoplasm etc.

Question 38

Which cell layer of the adrenal cortex synthesizes aldosterone?

Answer 38

The glomerulosa cells of the adrenal cortex synthesize aldosterone from cholesterol via progesterone. As with cortisol, no storage pool of presynthesized aldosterone is available in the glomerulosa cell for rapid secretion. Thus, secretion of aldosterone by the adrenal is limited by the rate at which the glomerulosa cells can synthesize the hormone.

Question 39

define secretagogue

Answer 39

a substance which promotes secretion.

Question 40

Name 2 physiologically more important secretagogues than ACTH for the stimulation of aldosterone production.

Answer 40

Although ACTH also stimulates the production of aldosterone in the glomerulosa cell, increases in extracellular [K+] and the peptide hormone ANG II are physiologically more important secretagogues. These secretagogues enhance secretion by increasing the activity of enzymes acting at rate-limiting steps in aldosterone synthesis.

Question 41

Once secreted, what % of circulating aldosterone remains free in plasma?

Answer 41

Once secreted, ~37% of circulating aldosterone remains free in plasma. The rest weakly binds to corticosteroid-binding globulin (CBG) (~21%) or albumin (~42%).

Question 42

CBG

Answer 42

Transcortin, also known as corticosteroid-binding globulin (CBG).

Question 43

The two primary mechanisms controlling aldosterone release are the

Answer 43

* renin-angiotensin system (RAS) * extracellular potassium K+

Question 44

RAS keeps the circulatory blood volume constant by promoting aldosterone-induced what exactly?

Answer 44

sodium retention during periods of hypovolemia and by decreasing aldosterone-dependent sodium retention during hypervolemia.

Question 45

independently of the RAS, what directly regulates aldosterone secretion

Answer 45

Plasma potassium ions

Question 46

In addition to RAS & K+, aldosterone secretion is influenced by several other factors such as: (3)

Answer 46

ACTH, natriuretic peptides, and a variety of neurotransmitters.

Question 47

AVP

Answer 47

arginine vasopressin which is the same this as ADH

Question 48

Renin is secreted by

Answer 48

juxtaglomerular cells of kidney

Question 49

Renin is secreted in response to (2)

Answer 49

A decrease in arterial blood pressure. A decrease in sodium load delivered to the distal tubule.

Question 50

What detects a decrease in arterial blood pressure in order to secrete renin?

Answer 50

vascular receptors in the afferent arteriole stimulate renin secretion in response to reduced renal perfusion pressure

Question 51

What detects a decrease in sodium load in order to secrete renin?

Answer 51

Na+ concentration of blood delivered to the distal tubule is measured by the macula densa cells of the juxtaglomerular apparatus.

Question 52

angiotensinogenase is also called

Answer 52

renin is a proteolytic enzyme which splits a leucine-valine bond of angiotensinogen which Yields decapeptide angiotensin I (biologically inactive).

Question 53

What converts angiotensin I to angiotensin II and where?

Answer 53

Angiotensin converting enzyme (ACE) in the lung

Question 54

Angiotensin II binds to AT1 receptors on zona granulosa cells and stimulates aldosterone biosynthesis. But it is also a very potent..?

Answer 54

vasoconstrictor and thus raises blood pressure via more than 1 mechanism

Question 55

Angiotensin II has a short half life of

Answer 55

~ 2 min

Question 56

name 3 effects of angiotensin II

Answer 56

effect on the hypothalamus to increase thirst effect on blood vessels, vasoconstriction effect on the adrenal cortex to produce aldosterone which increases Na+ and water retention = all increase blood pressure

Question 57

Potassium ions directly regulate

Answer 57

aldosterone secretion from the zona glomerulosa, independently of the renin-angiotensin system

Question 58

Name aldosterone's 3 effects on the kidney.

Answer 58

* Stimulates Na+ reabsorption (lowers Na+ excretion) * Lowers H2O excretion * Stimulates K+ excretion

Question 59

ACTH stimulates the secretion of the adrenocortical androgens, called?

Answer 59

dehydroepiandrosterone (DHEA) and androstenedione The adrenal androgens are weak hormones.

Question 60

Adrenal androgens are metabolically converted to

Answer 60

testosterone, and further into dihydrotestosterone

Question 61

what is the most abundant steroid hormone in the circulation.

Answer 61

dehydroepiandrosterone/DHEA, with its sulphate conjugate (DHEAS), is the most abundant steroid hormone in the circulation. The concentration of DHEA and androstenedione follows a diurnal rhythm similar to that of cortisol.

Question 62

chromaffin cells may also be called

Answer 62

pheochromocytes (cells of the adrenal medulla) can be regarded as modified postganglionic sympathetic neurons lacking axons.

Question 63

Adrenal catecholamines

Answer 63

Produced by adrenal medulla * epinephrine (also called adrenaline) * norepinephrine (also called noradrenaline)

Question 64

main effects of epinephrine (also called adrenaline)

Answer 64

this hormone increases the heart rate and force of heart contractions, facilitates blood flow to the muscles and brain, causes relaxation of smooth muscles, helps with conversion of glycogen to glucose in the liver, and other activities.

Question 65

main effects of norepinephrine (also called noradrenaline)

Answer 65

this hormone has little effect on smooth muscle, metabolic processes, and cardiac output, but has strong vasoconstrictive effects, thus increasing blood pressure.

Question 66

the major catecholamine secreted by the adrenal medulla of most mammals

Answer 66

epinephrine In whales and chicken norepinephrine dominates over epinephrine.

Question 67

Synthesis of catecholamines begins with what amino acid

Answer 67

Synthesis of catecholamines begins with the amino acid tyrosine which is taken up by chromaffin cells in the medulla and converted to norepinephrine and epinephrine.

Question 68

Secretion of norepinephrine and epinephrine is stimulated by

Answer 68

acetylcholine releasefrom preganglionic sympathetic fibers innervating the medulla. Manytypes of "stresses" stimulate such secretion, including exercise, hypoglycemia and trauma.

Question 69

The plasma half-life of catecholamines is

Answer 69

very short (1–3 min)

Question 70

adrenergic b-receptors (in particular b2-receptors) have a much higher affinity for

Answer 70

epinephrine than norepinephrine (whilst adrenergic a-receptors have about the same affinity for both)

Question 71

The effects of catecholamines depend on the

Answer 71

density of the different subtypes of receptors on specific organs and on the relative concentrations of epinephrine and norepinephrine. These effects are modulated by reflex mechanisms, e.g., as the blood pressure increases the heart rate is slowed and cardiac output tends to decrease.

Question 72

What is a Pheochromocytoma?

Answer 72

are catecholamine-producing neuroendocrine tumors arising from either chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. The latter are referred to as extra-adrenal pheochromocytoma or paragangliomas. Pheochromocytoma is considered to be rare in dogs and even less frequent in cats.

Question 73

Adrenocortical insufficiency two major forms are:

Answer 73

* (1) primary adrenocortical insufficiency due to lesions or disease processes in the adrenal cortices * (2) secondary adrenocortical insufficiency due to insufficient ACTH release by the pituitary. In addition to these conditions of absolute hormone deficits, there can be relative adrenocortical insufficiency.

Question 74

primary adrenocortical insufficiency is due to

Answer 74

lesions or disease processes in the adrenal cortices. results from progressive destruction of the adrenal cortices, which must involve 90% or more of the adrenocortical tissue before it causes symptoms and signs. The immune-mediated destruction typically terminates in absolute deficiencies of glucocorticoids and mineralocorticoids, together with high plasma levels of ACTH due to pronounced negative feedback to the hypothalamus and pituitary.

Question 75

secondary adrenocortical insufficiency is due to

Answer 75

insufficient ACTH release by the pituitary.

Question 76

Addison’s disease is

Answer 76

Primary adrenocortical insufficiency, The atrophy of the renal cortex is probably the end result of immune-mediated destruction. The immune-mediated destruction typically terminates in absolute deficiencies of glucocorticoids and mineralocorticoids, together with high plasma levels of ACTH due to pronounced negative feedback to the hypothalamus and pituitary. Thomas Addison in 1855 first described the syndrome in man, which at that time was usually the result of tuberculosis.

Question 77

Feedback loop: elevated cortisol inhibits

Answer 77

release of corticotropin (ACTH) by the corticotrophs in the adenohypophysis. it also inhibits release of corticotropin releasing-hormone by hypothalamic neurosecretory cells.

Question 78

Cortical adrenal tissue destruction may also be confined to the middle and inner zones of the adrenal cortex, resulting in what is known as

Answer 78

atypical primary hypoadrenocorticism. mineralocorticoid activity is retained which makes this condition easier to overlook. the symptoms and signs of typical or classic primary hypoadrenocorticism are absent.

Question 79

Primary hypoadrenocorticism may be part of a polyglandular deficiency syndrome. Concurrent endocrine gland failure may include (3)

Answer 79

primary hypothyroidism, type I diabetes mellitus, and primary hypoparathyroidism.

Question 80

Other possible causes of primary adrenocortical insufficiency, besides immune mediated tissue destruction (5)

Answer 80

* adrenocortical hemorrhage * fungal infection * metastatic disease * iatrogenic hypoadrenocorticism * Treatment of hypercortisolism with o,p'-DDD or trilostane may deliberately or unintentionally destroy the adrenal cortices.

Question 81

Clinical manifestations of Primary hypoadrenocorticism (dogs)

Answer 81

* primarily young to middle-aged dogs (mean four years) with a predilection for females. * There is breed disposition; Portuguese water dogs, poodles, and Nova Scotia duck tolling retrievers. It is an inherited disorder in some breeds. * Weakness * Fatigue * Anorexia * Vomiting * hypotonic dehydration

Question 82

Clinical manifestations of Primary hypoadrenocorticism (cats)

Answer 82

* VERY RARE * A disease of young to middle-aged animals * There have been two reported cases of primary hypoadrenocorticism in cats due to infiltration of the adrenals by malignant lymphoma. * Weakness * Fatigue * Anorexia * Vomiting * hypotonic dehydration

Question 83

Primary hypoadrenocorticism Patients presenting with acute collapse/addisonian crisis usually have evidence of

Answer 83

* Severe depression, * Weakness * hypotonic dehydration * generalized, marked hypovolaemia with hypotension * Vomiting * Diarrhoea * abdominal pain * hypothermia The clinical manifestations are primarily due to mineralcorticoid deifciency.