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The The Adrenal Gland Glandand the Stress and the Stress

ResponseResponse

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Aims To explore the role of the adrenal

glands in dealing with stress situations.

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Objectives Label a cross sectional diagram of the gross anatomy of the

adrenal gland

State the two catecholamine hormones secreted by the adrenal

medulla

Describe the key physiological responses stimulated in the adrenal

medulla in the ‘fight or flight’ response

Describe generalized physiological responses in fight and flight

State the major glucocorticoid hormone

State the 3 major actions of glucocorticoid hormones

State the 2 classifications of the gonadocorticoids (sex hormones)

State the major mineralocorticoid hormone

Describe 2 major actions of the mineralocorticoid hormones

(The term ‘corticoid’ indicates ‘produced in the cortex’)(The term ‘corticoid’ indicates ‘produced in the cortex’)

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Endocrine glands

The endocrine glands secrete hormones (chemical

regulators) into the circulation

These glands are also referred to as ductless glands,

and are very vascular

Once in the circulation these hormones then travel to

the target cells

Target cells respond to the hormone by an alteration in

their metabolism

These cells have specific receptor sites to which the

hormone will attach

[Exocrine glands (e.g. salivary ) secrete substances into

a duct.]

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The Adrenal Glands

The adrenal glands produce many different

hormones relating to:

– blood sugar

– mineral transport and fluid balance

– combating stress

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Anatomy of the adrenal glands

Adrenal glands lie in pairs above each kidney (they are "supra-renal“)

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Anatomy of the adrenal glands

Medulla

Zona Glomerulosa

Zona Fasciculata

Zona Reticularis

Capsule (connective tissue)

Zona Glomerulosa, Zona Fasciculata and Zona Reticularis are all part of the adrenal cortex

The adrenal medulla (10% of gland) is completely surrounded by the adrenal cortex (90% of gland) but the two parts differ both in structure and function

Anatomy of the adrenal glandAnatomy of the adrenal gland

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Anatomy of the adrenal glands

Medulla

Zona Glomerulosa secretes ALDOSTERONE

Zona Fasciculata secretes CORTISOL and ANDROGENS

Zona Reticularis secretes CORTISOL

and ANDROGENS

Capsule (connective tissue)

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ADRENAL CORTEX: Zona Glomerulosa

‘Grape-like’ clusters of cells that lie just under the capsule

Releases mineralocorticoids (steroid hormones of the adrenal cortex that regulate electrolyte imbalance)

Main mineralocorticoid = Aldosterone

Aldosterone release is regulated by the renin-angiotensin-aldosterone system (see later in sessions on BP, formation of urine, fluid and electrolytes)

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ADRENAL CORTEX: Zona Glomerulosa

Aldosterone stimulates distal tubules of kidney to pump sodium across basal membrane and thereby attract water

In this way aldosterone helps us to conserve both sodium and water

This raises extracellular fluid volume and hence blood pressure (see later in session on BP)

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ADRENAL CORTEX: Zona Fasciculata

The cells are arranged in cords (long rows) separated

by capillaries

Cells secrete GLUCOCORTICOIDS

Glucocorticoids are steroid hormones secreted by the

adrenal cortex [corticosteroids] that affect the

metabolism of glucose, protein and fat

Release of glucocorticoids is under the influence of

adrenocorticotropin [ACTH]

ACTH is a hormone from the anterior pituitary gland

that stimulates the adrenal cortex in response to

illness, injury, stress and ‘fight’ or ‘flight’ responses

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ADRENAL CORTEX: Zona Fasciculata

The main glucocorticoid in humans is CORTISOL which

is responsible for 95% of all glucocorticoid functions

Cortisol raises blood glucose levels, thereby providing

a source of energy for our responses to stress (in the

flight or fight reaction)

Cortisol is also anti-inflammatory (‘Hydrocortisone’)

(Cortex also produce corticosterone and cortisone –

about 5% of its production)

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Main actions of CORTISOL

1. Gluconeogenesis (‘creation

of new glucose’)

2. Providing resistance to

stress

3. Anti-inflammatory

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CORTISOL: GluconeogenesisGluconeogenesis is the creation of new glucose from non-

carbohydrate sources

i.e. the conversion of proteins and fat to glucose

Glucocorticoids also promote the storage of glucose as glycogen and inhibit glucose inhibit glucose utilization utilization (particularly (particularly in peripheral tissues)in peripheral tissues)

Both of these actions are essential for the maintenance of plasma glucose levels especially during period of prolonged fasting and dieting

Glucocorticoids promote promote lipolysislipolysis (breakdown of fat) and (breakdown of fat) and the consequent release of free fatty acids into the the consequent release of free fatty acids into the blood for blood for energyenergy production production

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CORTISOL: Providing resistance to stress

When exposed to stress (e.g. trauma, hypoglycaemia, perceived life threatening conditions )

anterior pituitary gland releases adrenocorticotrophic hormone (ACTH) adrenal cortex is stimulated to secrete glucocorticoids

increase in available glucose making the body and brain more alert and

provides the raw fuel for energy production.

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CORTISOL: Providing resistance to stress

CLINICAL POINT: If we are under constant stress we are

continually breaking down fat for glucose. If we run away from the stressor we will use

this fat up but if we do not the fat remains in the blood stream and can damage blood vessels, narrowing them as fat deposits lodge under the lining of the vessel walls.

This can in turn lead to the formation of clots, and this, coupled with an already increased blood coagulation can lead to potential for cerebrovascular accident (CVA – ‘stroke’) or heart disease

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CORTISOL: Anti-inflammatory actions

Glucocorticoid hormones inhibit the body’s inflammatory responses to infection, tissue damage, and invasion by foreign particles and proteins (‘anti’ inflammatory)

In this respect they serve to protect the body from excessive inflammatory responses and the potential for causing tissue damage

However this inhibitory effect does not occur when normal levels of glucocorticoids are secreted during everyday day situations and dealing with ‘positive stressors’ – if it did then the inflammatory response would never occur

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Negative feedback control of the adrenal cortex

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ADRENAL CORTEX: Zona Reticularis

This is the zone right next to the This is the zone right next to the medulla and  and  is seen as a branching network of smaller, dark is seen as a branching network of smaller, dark cellscells

These cells produce a group of hormones known These cells produce a group of hormones known

as as gonadocorticoids

They are regulated also by They are regulated also by ACTH

PrecursorPrecursor androgens androgens are turned into are turned into testosteronetestosterone in testes and in testes and oestrogenoestrogen in ovaries in ovaries

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The adrenal cortex produces steroids that regulate Na+ and K+ balance (mineralocorticoids), steriods that regulate glucose balance (glucocorticoids) and small amounts of steroid sex hormones (DHEA = Dehydroepiandrosterone)

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Adrenal Medulla

The adrenal medulla - inner part of the adrenal

gland

The medulla comprises 10-20% of the whole gland

Derived from embryonic postganglionic

sympathetic neurons / Part of the autonomic

nervous system

The cells of the adrenal medulla are neurons that

have lost their axonal processes and become

neuroendocrine cells

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The Adrenal Medulla The Adrenal Medulla secretes catecholamine

hormones: adrenaline (epinephrine) and nor-adrenaline (nor-epinephrine)

The effects of catecholamines are similar to those produced by activation of the sympathetic nervous system

The major function of the adrenal medulla (in combination with the sympathetic division of the autonomic nervous system) is to prepare the body to resist stress and to respond to emergency situations (the ‘fight’ or ‘flight’ response)

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Disorders associated with the adrenal medulla

An individual can live without the Adrenal Medulla but definitely not without the Adrenal Cortex

If it does need to be removed then individuals need corticosteroid supplements

If an individual develops a tumour of the adrenal gland the hormones produced may alter (e.g. women having two much testosterone developing masculine features, Cushing's Syndrome, Addison's Disease p.306 in Fox 2002)

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PART PART TWO

Stress and the ‘fight’ /’flight’

response.

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Defining Stress! Stress!

[many definitions]

“any physical or psychological threat to the

body, or to the maintenance of homeostasis” or

“any stimulus that creates an imbalance in the

internal environment, or imbalance in

homeostasis which may result in a change in

health status”

(Homeostasis: “ a condition in which the body’s

internal environment remains within certain

physiological limits”)

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Positive Stress

Not all instances where we feel under pressure or stressed have a negative effect upon the body

Some stress is can be therapeutic e.g. the stress involved in positive achievements e.g. at work, or in an exam, or when doing exercise, or in a social situation when meeting new people

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Stressors The stimuli that produce imbalances in

homeostasis are termed stressors These may be physical, psychological or social

in origin and may include: Mental and physical effort Extremes of temperature Fatigue Hypoglycaemia Changes in oxygen / carbon dioxide levels Infections Hypovolaemia Sudden or gradual environmental change Worrying and anxiety Perceived life threatening situations

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The Internal Environment and Homeostasis

Homeostasis of the internal environment will demand that physiological limits / ranges are maintained

Some examples: Glucose: 4-7mmol/L Blood pH: 7.35-7.45 Core body temperature: 36-37.50C Partial pressure of oxygen: 95-105 mmHg Sodium levels: 135-145mmol/L

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Control Systems and Homeostasis

The body responds to any imbalances in homeostasis via two complementary control systems:

– The Nervous System (quick acting)

– The Endocrine System (slow acting)

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Control Systems and Homeostasis

The Nervous System- quick acting via nerve impulses- stimulate cells / organs directly - respond to imbalance is rapid, short lived and may produce an immediate return to homeostasis

However if this does not occur then the ‘back up’ is:

The Endocrine System - slow acting via release of hormones from endocrine glands into the blood - these hormones are transported to distant cells and organs- they then produce an effect to rectify the imbalance

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Physiological responses to stress include Physiological responses to stress include

the integration of the following:the integration of the following:

The Reticular Formation

The Thalamus

The Cerebral Cortex

The Hypothalamus

The Limbic System

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Physiological responses to stressPhysiological responses to stress

The Reticular Formation - modulates mental alertness and skeletal muscle tone

The Thalamus - acts as a relay centre for sensory information

The Cerebral Cortex - facilitates increased vigilance, cognition and focussed attention

The Hypothalamus - modulates the function of both the endocrine and the autonomic nervous systems

The Limbic System - involved with emotions of fear, excitement, rage and anger

Physiological responses to stressPhysiological responses to stress

Musculoskeletal responses

Increased muscle tension

stiffness of the neck, backache and headaches

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ANS and Adrenal Medulla responsesRapid initiation of the ‘fight’ or ‘flight’ response

Adrenal Cortex responseRelease of cortisol maintenance of blood glucose alteration of the immune response

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Three stage model of physiological response to stress (Selye 1975 cited in Porth.C.(2002) Pathophysiology. Concepts of Altered Health States (Sixth edition). Lippincott : Philadelphia.

READ THE SECTION

Stage 1: The alarm reaction

Stage 2: The adaptation, resistance or counter-shock reaction

Stage 3: The stage of exhaustion

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Stages of stress

Alarm reaction- basically equates to the ‘fight’ or ‘flight’ response - cortisol is also released and no one organ is

predominantly activeAdaptation, resistance or counter-shock reaction.- body attempts to return to a steady homeostatic

state or adapt to the new situation via the continued actions of adrenal and other hormones

Stage of exhaustion. - if the body’s attempts to overcome the effects of

the stressor(s) fail and if the adaptation does not occur this will lead to problems such as gastric ulceration, reduced oxygen supply to cells and ultimately death

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The Adrenal Medulla and the Fight or Flight Response

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Fight or Flight Response

When exposed to a stressful event (e.g. hypovolaemia, perceived life threatening event)

impulses initiated in the hypothalamus and brain stem are transmitted via sympathetic neurons to the adrenal medulla

Adrenaline is released into the blood and carried to target cells / organs which are stimulated to resist stress via the FIGHT or FLIGHT response

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Fight / Flight responses

Iris (eye muscle) Pupil dilation allows more light to enter eye

Salivary Glands Saliva production reduced

Oral/Nasal Mucosa Mucus production reduced

Heart Heart rate and force of contraction increased

LungBronchial muscle relaxed. Increased breathing

Stomach Peristalsis reduced

Small Intestine Motility reduced

Large Intestine Motility reduced

LiverIncreased conversion of glycogen to glucose providing more energy for muscle contraction

Kidney Decreased urine secretion

SkinConstriction of skin arterioles, pallor, hair stands on end / ‘gooseflesh’.

BladderWall relaxedSphincter closed

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The release of adrenaline and nor-adrenaline from the adrenal medulla and their subsequent actions

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CRH = corticotrophin releasing hormone; PVN = paraventricular nucleus; ADH = antidiuretic hormone.

General model for the coordination of the immediate response to stress