Presentation by Dr. Ali Garatli on Stress and its management for King Fahd Medical City staff in Riyadh, Saudi Arabia

1. STRESS
ALI GARATLI,MD
KFMC

2. Package

3. Stress Response Savior to Killer232.flv

4. The Stress Response System
Cannon proposed that
the stress response
(fast) was a fight‐or‐
flight response marked
by the outpouring of
epinephrine and
norepinephrine from
the inner adrenal
glands, increasing
heart and respiration
rates, mobilizing sugar
and fat, and dulling
pain.

5. Physiological Responses to
Stress
Endorphins are released
Pupils dilate to admit more light for more
sensitive vision
Mucous membranes of nose & throat shrink
while muscles force wider opening of passages to
permit easier air flow
Heart rate increases
Liver releases sugar into blood stream –
energy for muscles and brain
Bone marrow throughout body produces
more while blood cells
Voluntary skeletal muscles contract throughout
the body
Hearing becomes more acute
Secretion of saliva decreases
Bronchi dilate
Perspiration increases –
evaporation cools body
Spleen releases more red blood
cells
Pancreas decreases secretion
Adrenal glands release adrenalin
and noradrenalin resulting in
increased blood pressure, increased
heart rate, increased fatty acids in
blood stream and increased blood
sugar

6. CRF & Stress
CRF plays an important role in stress
response
Stress exposure is associated with ↑
CRF
Central CRF administration is
associated
with fear-related behaviors
↓ exploration
↑ startle
↓ grooming

7. Main biological pathways of
chronic stress:
- Dysregulation of the hypothalamushypophysis-adrenocortical (HPA) axis and the
sympathetic-adrenal-medullary system (SAM)
resulting in elevations in serum
catecholamin and cortisol levels.
Sympathoadrenal hyperactivity contributes to
the development of CVD through effects of
catecholamines upon the heart, blood vessels
and platelets.
Sympathoadrenal activation modifies the
function of circulating platelets

8. Stress and Illness
Leading causes of death in the US in 1900
and 2000

9. Stress and Disease
Negative emotions and health-related
consequences
Heart
disease
Persistent stressors
and negative
emotions
Unhealthy behaviors
(smoking, drinking,
poor nutrition and sleep)
Release of stress
hormones
Immune
suppression
Autonomic nervous
system effects
(headaches,
hypertension)

10. stress
is the result of the
perceived demands outweighing the
perceived capability to cope
This perception is influenced by a
number of factors:
personality,
situational demands,
previous experiences
Resources
any current stress state already existing

11. Good things about stress
Sometimes it will save your life, or help
you
Fight
Accident
Test…

12. Stressful Life Events
Chronic Stress by Age

13. Stress and Individual
Differences
Hardiness
A characteristic of people who can tolerate
stress well or even thrive on it
Resilience
Ability of a person to “bounce back” after a
stressful event
Self-imposed stress

14. Coping With Stress
Direct coping
Intentional efforts to change an uncomfortable
situation
Confrontation
⌧Acknowledging stress directly and initiating a solution
Compromise
⌧Choosing a more realistic goal when an ideal goal cannot be
met
Withdrawal
⌧Avoiding a situation when other options are not practical

15. Compromise

16. Sources of Extreme Stress
Unemployment
Stages of relief, optimism, doubt, malaise,
cynicism,
Divorce and separation
Ambivalence, feelings of failure, sadness,
and fear
Bereavement
‫اﺳﻬﻢ‬

17. Signs of stress
Physical: headache, sleep disorders, racing
heart, trembling, wt loss or gain
Mental: constant worry, forgetfulness, mood
swings, loss of sense of humor
Emotional: anger, anxiety, negative thinking
Behavioral: critical attitude of others,
impulsive actions, withdrawal from relations,
alcohol abuse

19. Gender differences
There are no fundamental gender differences in
physiological adaptation processes
Although male and female hormones influence it in both
respect
Estrogenes decrease the stress reactivity
According to animal studies, males appear to be more
vulnerable to long-lasting stress-induced
hippocampal damage than females (Uno et al, J.
Neurosci,9,1705-1711,1989), the decline of circulating
testosterone levels resulting from uncontrollable stress
seems to play an additional role.
Perinatal processes might result in dysregulation- postnatal depression

20. •Improper functioning of the subunit could
impair the GABA system’s ability to adapt
to hormone fluctuations during the highly
20
vulnerable post partum period

21. Package

22. Started before conception
Stress in pregnant mother can have
detrimental effect .
Increased cortisol , fetus will shift to a
protection mode , from growth mode
Child will be vulnerable for later CAD, DM

23. Early life chronic stress:
Phases of disruption of mother-infant
or peer bonding:
1. "protest" behaviour (acute and
resistance phases of stress).
2.“despair”: locomotor inactivity and a
disinterst in motivationally salient
external stimuli.
3."detachment""hardwired" in the
brain of many social mammals and
results in high stress vulnerability

24. Attachment theory (Bowlby,
Imre Hermann)
Physiological, psychological and
developmental importance of the early
childhood affective mother-child bond and
the negative consequences of the disruption
of this relationship.
According to follow up studies, insecure
attachment predicts later emotional
instability and health deterioration.
Maltreatment at an early age can have
enduring negative effects on a child’s brain
development and function, and on his or
her vulnerability to stress.

25. Special gender roles, crucial
effect of maternal care
Maternal neglect behaviour results in
attachment disturbances
Naturally occuring variations in
maternal care alter the expression
of genes that regulate behavioral and
endocrine responses to stress, as
well as hippocampal synaptic
development – related to oxytocin
receptor gene expression (M.J.Meaney: Ann Rev
Neurosci2001, 24,1161-1192)

26. Learned helplessness as
result of chronic stress
A condition of loss of control created by
subjecting animals or humans to an
unavoidable, emotionally negative life
situation (such as unavoidable shocks,
relative deprivation, role conflict, etc).
Being unable to avoid or escape (flight
or fight) an aversive situation for a long
period of time produces a feeling of
helplessness that generalises to
subsequent situations.

27. Brain consequences of
learned helplessness:
The hippocampus is primarily affected
by the long-lasting elevations of
circulating corticosteroids resulting
from uncontrollable stress. Severe
stress for a prolonged period causes
damage in hippocampal pyramidal
neurons, especially in the CA 3 and CA4
region and reductions in the length and
arborization of their dendrites.

28. Stress and Illness
The body’s resistance to stress can
last only so long before exhaustion sets in
Stress
resistance
Stressor
occurs
Phase 1
Alarm
reaction
(mobilize
resources)
Phase 2
Resistance
(cope with
stressor)
Phase 3
Exhaustion
(reserves
depleted)
General
Adaptation
Syndrome
Selye’s concept
of the body’s
adaptive
response to
stress in three
stages

29. Stage 1: Alarm
= stress response – stressor has been
detected and a response made to alarm.
Adrenaline is produced leading to fight
or flight activity.

30. Stage 2: Resistance
= Apparent coping, if stress continues
it is necessary to find some means of
coping and resist collapse. In this stage
the body is adapting to the demands of
the environment, but at the same time
resources are being used up. Thus =
apparent coping because in reality things
are deteriorating

31. Stage 3: Exhaustion
= breakdown, onset of stress-related illness.
Eventually the body can no longer maintain
normal functioning.
Initial physiological changes may appear,
e.g. sweating, increased heart rate. The
adrenal gland (produces adrenaline) may be
damaged due to over activity and the
immune system may unable to cope due to
the production of proteins being needed
elsewhere = ulcers, depression,
cardiovascular problems etc

32. More GAS
3) Exhaustion
Defenses depleted at this point
Very vulnerable
Lots of this is bad
Leads to destruction of hippocampal cells caused
by cortisol release
So, memory loss!

33. Hippocampal Volume Reduction
In PTSD
NORMAL
PTSD
MRI scan of the hippocampus in a normal control
& patient with PTSD secondary to childhood
abuse. The hippocampus, outlined in red, is
visibly smaller in PTSD. Overall 12% reduction in
volume in PTSD.
(Bremner 1995; Bremner
1997)

34. Stress
Antidepressants
↑ Cortisol
↑
Normal
Serotonin & NE
↑
↑ BDNF
↓BDNF
Normal
Survival &
Growth
Cortisol
↓
Atrophy & death
Survival & Growth
& Growth
Other neuronal
insults:
Genetic Factors
Factors
Hypoxia-Ischemia
Hypoxia-Ischemia
Hypoglycemia
Hypoglycemia
Neurotoxins
Neurotoxins
Viruses
Viruses
( Duman, Heninger &
Nestler 1997)

35. Questions
Can stress, anxiety, depression, social support,
and optimistic view alter our ability to resist
infection, autoimmune diseases or cancer?
What are the biological pathways through which
psychological state or characteristic will
influence in disease susceptibility?
Can we alter immunity and therefore disease
susceptibility through psychological
intervention?

36. 1981 David Felten: Discover a “hard-wire connection between the
immune system and the CNS (trace nerves to bone marrow,
lymph nodes, thymus and the spleen)
Psychoneuroimmunology (PNI): study of interrelations
between the CNS and the immune system (David Felten, 1981)
Existence of neurologic terminations directly into lymphoid
tissues in the spleen and release of neurochemicals in this
location
2000 Bellinger: NA innervation of BM, thymus , spleen and nodes
in animal models (immune system cells have adrenergic receptors
receptors for NE ): Herbert, 1994; Bachen, 1995
Human research: establish the association between psychological
states and immunity

37. Psychoneuroimmunology
B lymphocytes fight bacterial infections, T
lymphocytes attack cancer cells and viruses, and
microphages ingest foreign substances. During
stress, energy is mobilized away from the
immune system making it vulnerable.
Lennart Nilsson/ Boehringer Ingelhein International GmbH

38. Immunity and Disease
How the immune system works

39. Stress and Colds
People with the highest life stress scores were also
the most vulnerable when exposed to an
experimental cold virus.

40. Stress and Heart Disease
Adrena
l
CORT
EX
Adrenal
MEDUL
LA
Cortisol
(associated with
long-term effect
of stress) – loss
of control
Adrenalin
(associated with
acute or short
term response
to stress.
Increased FFA,
increased
Platelet
numbers,
increased
Serum
Cholesterol,
decreased
Potassium,
direct injury
producing
effect of
coronary
artery walls.

41. Increased Platelet stickiness,
direct injury producing effect on
coronary artery walls,
over contractibility of myocardium,
increased FFA, shearing effect on
plaques
resulting in clotting system.

43. GP IIb/IIIa Receptor Final
Pathway to Platelet
Aggregation
o Platelet activation and aggregation are early
events in the development of coronary
thrombosis
o GP IIb/IIIa receptors on activated
platelets undergo a conformational change
allowing recognition and binding of
fibrinogen
o Fibrinogen”acts like glue”,bridging GP
IIb/IIIa recptors on adjacent platelets,
leading to platelet aggregation

44. Pathophysiology in Motion

45. y
Increases the Risk of a
Heart Attack
1. Stress Hormones (Cortisol & Adrenaline)
elevate Blood Pressure.
2. Adrenalin increases blood platelet stickiness.
3. Cortisol increases blood platelet numbers.
4. Adrenalin & Cortisol have a direct injuryproducing effect on artery walls (contributes
to atherosclerosis).
5. Adrenaline causes over-contractibility of
heart muscle (rupture fibers?).
6. Cortisol increases cholesterol levels and
lowers potassium levels.

46. INTERHEART: Measured
Factors

47. Stress and the Heart
Stress that leads to elevated blood pressure may
result in coronary heart disease, a clogging of the
vessels that nourish the heart muscle.
Plaque in
coronary artery
Artery
clogged

48. Stress and the Heart
Hopelessness
scores
3.5
3
Men who feel extreme hopelessness
are at greater risk for heart attacks
and early death
2.5
2
1.5
1
0.5
0
Heart attack
Low risk
Death
Moderate risk
High risk

49. Stress and
type A’ person
,competitive, hostile /aggressive, timeconscious, ‘workaholic’ and easily
frustrated with others.
Respond to life events with impatience
and hostility
70%of this sort of person died from
heart attacks –
Have two fold risk of CV disease and 5fold risk of MI
1970s, Friedman and Rosenman

50. Stress and the Heart

51. Stress, Depression and Heart
Disease
Managing Stress
Learn to accept things you can’t change.
You don’t have to solve all of life’s
problems
Count to 10 before answering or
responding when you feel angry
Don’t use smoking, drinking, overeating,
drugs or caffeine to cope with stress
.
They make things worse

52. Coping with stress
Assert yourself: honest and upfront
Exercise regularly
Control what you can and leave that you cant
Examine your values and live by them
Set realistic goals
Sell yourself to yourself
Get enough rest sleep in the dark, early night
Eat and drink sensibly
Stop smoking
meditation
Keep positive attitude

54. Negative Self Talk
words our inner dialogue uses when we think
can increase our stress levels by limiting our potential
Can color our experience in a negative light
When you tell yourself something is ‘difficult’ or
‘unfair’, it becomes more stressful to deal with than
if you tell yourself it’s a ‘challenge’, or even a ‘test’
Patterns of negative self-talk typically begin in
childhood
the negative self-talk habit may have been coloring
thinking for years
CBT

56. Promoting Positive Self Talk
1. Notice your patterns: The first step
toward change is to become more aware of
the problem. You may not realize how often
you say negative things in your head, or how
much it affects you
2. Journal Writing: keeping a journal can be
an effective tool for examining your inner
process.
3. Thought-Stopping: As you notice yourself
saying something negative in your mind, try
to alter your thought mid-stream my saying
to yourself “Stop”.

57. Methods of Reducing
Stress
Calm down
Exercise
Relaxation training
Reach out
Social support network
Religion
Studies have shown an association between religion and lower
stress
May be related to social support
Altruism
Giving to others because is gives you pleasure
Shown to be a good way to reduce stress

58. Coping With Stress at
College
Plan ahead
Prioritize
Exercise
Listen to music, watch TV, or go out as a
study break
Talk to others
Meditate or use other relaxation
techniques

59. The Key Word Is….
Balance

60. Sleep-Wake Cycle:
Role of Endogenous Melatonin
Circadian and Homeostatic Regulation of Sleep
Sleep
Drive
Wake
Wake Propensity
Melatonin
Circadian
Alerting
Signal
9 am
Awake
3 pm
9 pm
3 am
Asleep
9 am
Sleep