BBT307/BB417

Prepared by Ishrat Jabeen (PhD)

Fall 2020
Lecture 12

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Respect your parents, respect your teachers

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Cortisol Effects: Body Responses to Stress

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Circadian rhythm of cortisol secretion
Cortisol Effects: Body Responses to Stress
• Permissive effect on glucagon

• Memory, learning & mood

• Gluconeogenesis

• Skeletal muscle breakdown

• Lipolysis, calcium balance

• Immune depression

• Circadian rhythms
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Cortisol: Role in Diseases and Medication

• Use as immunosuppressant
• Hyperimmune reactions
• Serious side effects

• Hypercortisolism (Cushing's syndrome)

• Tumors (pituitary or adrenal)
• Iatrogenic (physician caused)

• Hypocortisolism (Addison's disease)

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 Overuse and increased amounts of Corticosteroids should be avoided and
should only be used sparingly

Reasons why therapeutic use should be limited:

1) Persons using have limited ability to resist infections

2) Other undesirable effects can occur such as: a) Gastric ulcers b) ↑blood
pressure c) atherosclerosis d) menstrual irregularity.

3) High levels of exogenous corticosteroids can lead to irreversible atrophy of

the cortisol-secreting cells of the adrenal gland and later permanent inability
of the body to produce cortisol.

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 Regulation of Cortisol release
Two factors that can also influence the negative feedback are diurnal variation in cortisol and
stress.

1) Cortisol levels are highest in the morning and lowest at night. This is primarily related to
the sleep-wake cycle. They will be reversed in one who works nightly and sleeps daily.
This information is particularly important to know:

1) when blood sample is taken;

2) the sleep cycle of person being sampled or swing shifts; and

3) the effect of surgery time of day in helping the individual handle the stress.

2) Stress can greatly affect levels of cortisol in the blood. It can override, for example, the
hypothalamic-pituitary axis of negative feedback. The magnitude of the increase of blood
cortisol is proportional to the intensity of the stressful stimulation. More stress – more
cortisol. Less stress- less cortisol. 7
hypothalamic-pituitary axis of
negative feedback

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Cortisol presence allows for permissiveness

❑Cortisol presence permits catecholamines to induce vasoconstriction. If not, a

person lacking cortisol, may go into circulatory shock (decrease in blood volume
or blood pressure) in a stressful situation that needs widespread vasoconstriction.

❑Cortisol and Stress.

Stress is defined as the generalized nonspecific response to the body to any factor
that overwhelms, or threatens to overwhelm the body’s compensatory abilities to
maintain homeostasis. The stressor is the agent inducing the response while
stress is the state induced by the stressor.

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 Effects of Stress
Physical Effect Behavioral Effect
• Heart disease • Irritability
• Digestive problems • Anger
• Elevated cholesterol levels • Worry
• Elevated blood pressure • Anxiety.
• Weakness • Depression
• Weight loss • Excessive smoking
• Chronic pain • Nervous tics
• Asthma • Increased use of alcohol or drug(s)
• Allergies • Mannerisms like nail biting, hair puling

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Control of Cortisol Secretion: Feedback Loops
• External stimuli
• Hypothalamic
• Anterior Pituitary
• Adrenal cortex
• Tissues

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What are the stages of stress and adaptation to stress?
• Stage 1: The Alarm Reaction (sympathetic-adrenomedullary system)

• Stage 2: The Stage of Resistance (Hypothalamic-pituitary-adrenal axis)

• Stage 3: The Stage of Exhaustion

• How does this apply to you when a mugger jumps from around a corner?

• How does this apply to a soldier who has been in the field under fire for two
months and come home on leave?

• How does this apply to a loved one who is finally succumbing to cancer?

• Why is it clinically important to consider the stage of stress that a person is

experiencing? https://www.youtube.com/watch?v=XADIs-A1iiM

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 Types of stimuli that can induce a stress response:
Physical - trauma, surgery, intense heat or cold, restraining the person
Chemical - ↓O2 supply, acid-base imbalance
Physiological – heavy exercise, pain, hemorrhagic shock
Psychological or emotional – anxiety (Exams, Midterms☺), fear, sorrow
Social – personal conflicts, changes in lifestyle
❑Any of these stresses can cause an immediate and marked increase in ACTH from the anterior
pituitary thereby causing an increase in cortisol from the adrenal cortex.

❑Why cortisol is released in stress is unknown but consider the example of a primitive human or
animal faced with life threatening situation where eating is not a plausible event at that time.

❑Result is increase blood glucose for the brain, increase free fatty acids for energy and increase amino
acids for liver proteins.

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 Adrenal Medulla:
A Modified Sympathetic Ganglion
• Sympathetic stimulation
• Catecholamine release to blood
• Epinephrine
• Norepinephrine
• Travel to:
• Multiple targets
• Distant targets

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Adrenal Medulla:
A Modified Sympathetic Ganglion

Figure 11-10: The adrenal medulla 18

Review of Efferent Pathways: Motor & Autonomic

NE produces
vasoconstriction of most NE and Epi both increase the
organs via α1 receptor. force and rate of the heart
contraction via β1 receptor.

Epinephrine dilates the

blood vessels in skeletal
muscle and the liver via β2
receptor.
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https://www.youtube.com/watch?v=H1qUpuf0ZP4

• Metyrosine is an inhibitor of
the enzyme TYROSINE 3-
MONOOXYGENASE, and
consequently of the
synthesis of catecholamines.
• Reserpine is an adrenergic
blocking agent used to treat
mild to moderate
hypertension via the
disruption of
norepinephrine vesicular
storage.
• Tricyclic
antidepressants (TCAs) are
a class of medications that
are used primarily
as antidepressants.

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Review of Efferent Pathways: Motor & Autonomic

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THE ADRENAL MEDULLA CONTAINS A LARGE NUMBER OF CELLS THAT
RELEASE EPI/NE INTO THE BLOOD (INSTEAD OF A SYNAPSE) so the
catecholamines are delivered to the entire body!

❑ Sympathetic Nervous System has two ways to deliver info:

1) Preganglionic axons innervate postganglionic cell that releases EPI/NE into a specific
synapse on a specific target cell in a specific tissue.

2) Preganglionic axons innervate postganglionic cells of the adrenal medulla that store
EPI/NE in vesicles. Exocytosis is used to secrete NE and EPI into interstitial fluids followed
by diffusion through fenestrations to blood. Epi/Ne diffuses from blood through
interstitium to target adrenergic receptors located on platelets, endothelial cells, or cells in
tissues (i.e. heart).

• THESE ARE TWO “REDUNDANT” DELIVERY METHODS!

• Why is redundancy important to cardiac function if you have a transplanted heart?
• Adrenergic receptors on target cells are very selective and only accept EPI or NE
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5 different types of adrenergic receptor

❑ Heart: ↑Force of Contraction: Beta 1 (+ adenylyl cyclase)

❑ Lung: ↑Bronchodilation: Beta 2 (+ adenylyl cyclase)

❑ Fat: ↑Energy release via Beta 3 (+ adenylyl cyclase)

❑ Vasoconstriction/↑Heart Rate: Alpha 1 (+phospholipase C)

❑ Inhibition (IPSP:↑intracellular K+): Alpha 2(-adenylyl cyclase)

EACH RECEPTOR GIVES A DIFFERENT EFFECT!

https://www.youtube.com/watch?v=ZDS3vJ_qTQ8

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