Adrenal Glands & Physiology of stress

Question 1

How many adrenal glands do we have?

What happens when one is removed?

Answer 1

2

The other gets bigger.

Question 2

What 3 parts is the adrenal correct split into and what does each part make?

Answer 2

Zona glomerulosa - mineralcortocoids (aldosterone)

Zona fasciculata - glucacorticoids (cortisol)

Zona reticularis -
glucacorticoids and some androgens

Question 3

What does the medulla secrete?

Answer 3

Adrenaline (80%)

Noradrenaline (20%)

Question 4

Give small details on adrenal histology

Answer 4

Fasciulata - cords of cells
Reticularis also has cords but are smaller.
Glomerulosa cells form below the capsule and then migrate in and go from making aldosterone to making cortisol.

Question 5

How aldosterone works:
• The mineralocorticoid (comes from cortex and is involved in salt balance) aldosterone is produced exclusively in the zona —-.
• It acts on the distal tubules and collecting ducts of the kidney to promote Na+ —- (to reabsorb it - without aldosterone, we lose sodium in urine and plasma osmolarity falls and we lose plasma volume aka water) and enhances K+ elimination in urine.
• Promotion of Na+ retention induces osmotic retention of —-, causing expansion of the ECF volume, which is important in the long-term regulation of blood pressure.
• Mineralocorticoids are essential for life. Without aldosterone, a person rapidly dies from circulatory shock because of the marked fall in —- —- caused by excessive loss of Na+.
Aldosterone secretion is stimulated by activation of the renin-angiotensin system in response to a reduction in —-and a fall in blood volume. This is —- of anterior pituitary control. When the kidney detects a fall in blood volume, renin is released which activates —- which activates aldosterone).

Answer 5

glomerulosa

retention

water

plasma volume

Na+

independant

angiotensin

Question 6

How does cortisol work?

Answer 6

It plays an important catabolic role in carbohydrate, protein and fat metabolism to generate an increased pool of glucose, amino acids and fatty acids for use as needed - releases fuel to allow you to respond to stress.

Question 7

Adrenal medulla:

• What is it part of?
• What is it composed of?
• How do the hormones get released?
• What hormones does it secrete?
• What are stored in vesicles here and why?

Answer 7

Part of the sympathetic nervous system.

• The adrenal medulla is composed of modified postganglionic sympathetic neurons (chromaffin cells).
• They have no axons, but the cells release their chemical transmitter directly into the circulation upon stimulation by the preganglionic nerves.
• The adrenal medulla secretes both noradrenaline (20%), and adrenaline (80%).
Catecholamines are stored in vesicles and released into the circulation by exocytosis in response to acute stress. This is a rapid action telling us adrenaline and noradrenaline have rapid effects.

Question 8

What is stress and what can it be caused by?

Answer 8

• Stress refers to the generalised non-specific response of the body to any factor that overwhelms, or threatens to overwhelm, the body’s compensatory abilities to maintain homeostasis.
• The agent inducing the response is correctly called a stressor. • Thus stress refers to the state induced by the stressor.

Stressors
Physical: trauma, surgery, intense heat or cold.
Chemical: reduced O2 supply, acid-base imbalance
Physiological: heavy exercise, haemorrhagic shock, pain.
Psychological (emotional): anxiety, fear, sorrow.
Social: personal conflicts, change in lifestyle.

Question 9

What are the 3 phases of stress?

Answer 9

1) Alarm (fight/flight, short term, adrenaline)
2) Resistance to stress (chronic, cortisol levels elevated)
3) Exhaustion (immune suppression, illness, death)

Question 10

What is the role of the hypothalamus in phase one?

What endocrine responses are there?

Answer 10

The hypothalamus activates the sympathetic division of the Autonomic Nervous System (ANS), while generally inhibiting parasympathetic control of dually innervated organs.

Endocrine response:

1) Increases sympathetic activation (noradrenaline)
2) Adrenaline release from medulla
3) Increased circulating (nor)adrenaline

Question 11

What affects do noradrenaline and adrenaline have on the body?

Answer 11

• increased glycogenolysis (liver, muscle), provide glucose (for skeletal muscle)
• increased lipolysis, provide glycerol and fatty acids
• increased cardiac output (more oxygen for muscle and quicker excretion of waste)
• divert blood flow from viscera to skeletal muscle
• increase ventilation (bronchodilation, respiration rate)

Question 12

What happens in the hypothalamus after 2-3 mins of the stressor?

Answer 12

This activates the adrenal cortex and controlled by anterior pituitary which is controlled by the hypothalamus.

Neurones project to the hypothalamus (the medium eminence).
Neurons make small peptides, made in cell body and transported down. This enters the portal circulation and carries the peptide to the anterior pituitary.
The peptide is the corticotrophin releasing factor. This controls the release of ACTH from the anterior pituitary.
ACTH released from the anterior pituitary enters the venous drainage to be transported to the adrenals.

Question 13

Explain the mechanism of cortisol secretion and hence ACTH synthesis and secretion
(negative feedback)

Answer 13

• Cortisol secretion is regulated by a negative-feedback system involving the hypothalamus and anterior pituitary.
• ACTH is synthesised in corticotroph cells in the anterior pituitary.
• ACTH secretion is controlled by the hypothalamic secretion of corticotropin-releasing hormone (CRH).
• ACTH stimulates both the growth and secretory output of the two inner layers of the adrenal cortex.
- The feedback loop is completed by cortisol’s inhibitory actions on CRH and ACTH secretion by the hypothalamus and anterior pituitary, respectively.

Question 14

What are short term affects that cortisol has?

Answer 14

Catabolic effects: opposite those of insulin, maintains metabolic enzyme expression.
• stimulate protein breakdown in muscle, bone, liver, etc. • stimulate hepatic gluconeogenesis
• stimulate lipolysis to generate FA and glycerol
Clinically important because of protein catabolism associated with illness/surgery; insulin requirement in diabetes.

Question 15

What long term affects does cortisol have?

Answer 15

Enhances cardiovascular reactivity to catecholamines
• allows vasoconstriction in response to (nor)adrenaline
Clinically important because chronic stress can cause hypertension; low/absent cortisol can cause hypotension

Question 16

Give the behind the inhibition of the inflammatory and immune responses

Answer 16

• inhibits PG and LT production (these molecules cause inflammation)
• inflammatory cytokines stimulate ACTH, hence cortisol secretion in a –ve loop to damp down inflammatory responses. Inflammation stimulates ACTH, ACTH inhibits inflammation.
Clinically important as anti-inflammatory therapy
but
Prolonged use has severe side effects (Cushings), including down-regulation of ACTH secretion and adrenal atrophy
Chronic stress suppresses immune system = infection

Question 17

What are the lasting long term affects of cortisol for life?

Answer 17

Inhibits non-essential functions (reproduction and growth)
• reductions in bone density, skin thickness, muscle mass, etc as catabolic processes generate fuel
• chronic stress/elevated cortisol in childhood may cause growth retardation • chronic stress in adults may reduce fertility. This is reversible.
Clinically important as side effects of cortisol therapy

Question 18

Outline some stress related diseases

Answer 18

• Acceleration of cardiovascular and respiratory activity, retention of water and salt, and mobilisation of metabolic fuels (catabolic affects in muscle, liver, adipose and bone and building blocks can be of benefit in response to physical stressors.
• These responses may be inappropriate if the stressor is psychological. Chronically increased plasma cortisol can decrease immune system activity enough to reduce resistance to infection and, perhaps, cancer.
• Symptoms of diabetes are worsened by increased insulin resistance.
• Prolonged and repeated sympathetic activation by psychological stress may enhance the development of atheroschlerosis and hypertension.

Question 19

Explain the last phase of stress

Answer 19

(3) Exhaustion
• The price paid by the body during stress arises because cortisol is strongly catabolic.
• Cells of the immune system, bone, muscles, skin and many other tissues and glands undergo catabolism to provide substrates for gluconeogenesis.
• This can lead to severe decreases in bone density, immune function and reproductive fertility.
Ultimately metabolic resources can be depleted beyond recovery – exhaustion. immune suppression, illness, death

Question 20

What is addisons disease?

What are the affects of it?

Answer 20

Inability to respond to stress.
Adrenal cortex gets damaged by tuberculosis or by autoimmune destruction.

Adrenal insufficiency cause:
- hypotension, hypoglycaemia, tiredness, weakness, anorexia, vomiting, depression