Download 1 2 - UMSONPatho

Homeostasis and The Stress
Response
1
Homeostasis
2
Homeostasis
• Definition: The tendency of an organism or a cell to regulate
its internal conditions, usually by a system of feedback
controls, so as to stabilize health and functioning, regardless
of the outside changing conditions. http://www.biologyonline.org/dictionary/Homeostasis
• Influences that tend to deregulate internal conditions are
termed “stressors”
– This is a different definition than we are used to hearing
• Stressors can be physical, emotional, environmental, etc.
• Compensatory mechanisms to counteract the effect(s) of
stressors involve
–
–
–
–
Autonomic nervous system
Adrenal cortex
Renin-angiotensin-aldosterone system (RAAS)
Many others.
3
Stressors
4
Stressors
5
Three Components to Physiologic
Stress Response
6
Three Components to Physiologic
Stress Response
3. Adaptation
response &
return to
homeostasis
1. Stressor
2. General
adaptation
syndrome
7
Neuroendocrine Pathways and
Physiologic Responses to Stress
Description
8
Neuroendrocrine Pathways and Physiologic
Responses to Stress
Description
• Shows the different responses to stressors
• May perceive stressor in the cerebral cortex or
the stressor may be unconscious
– Activating the RAS (the part of the brain that
keeps up awake) – leads to increased muscle
tension and alertness
– Limbic system produces the emotional response
• The locus ceruleus activates the ANS (sympathetic
nervous system), which activates the adrenal medulla
and the activation of the RAAS
9
Neuroendrocrine Pathways and
Physiologic Responses to Stress
Diagram
10
Neuroendrocrine Pathways and Physiologic Responses to Stress
(Corticotropin
Releasing Factor)
(Adrenocorticotropic
Hormone)
Activation of the RAAS
Adapted from Porth, 2011,
Essentials of
Pathophysiology,3rd ed.,
Lippincott, p. 213
11
Activation of the Sympathetic
Nervous System (SNS)
12
Activation of the Sympathetic Nervous
System (SNS)
•  Heart rate
•  Blood pressure
• Cool skin
– All of the blood is being
shunted away form the
skin to the skeletal muscle
• Diaphoresis to keep body
cool
• Pupil dilation
•  Blood glucose to have
fuel for muscle
•  Peristalsis
•  Urine output
– Do not want to devote
metabolic energy to urine
formation
13
Release of Norepinephrine
14
Release of Norepinephrine
Norepinephrine
1
 1 2
1
Vasoconstriction
of arteries and veins
(↑Venous return to the heart/CO
and ↑Blood Pressure)
Pupil Dilation
Heart rate
Contractility
Release of renin
All of these increase blood
pressure
15
Epinephrine Released by
Adrenal Medulla
16
Epinephrine Released by
Adrenal Medulla
-Activates alpha 1 and
alpha 2 as well as beta
1  2
2 receptors
Vasoconstriction
Epinephrine
1
1
Blood pressure
2
Pupil dilation
Venous return/CO
Heart rate
Contractility
 Release of renin
Dilation of skeletal
muscle vascular beds
and bronchi
17
Role of Epinephrine on B2
Receptors
18
Epinephrine
2
Lipolysis of triglycerides
2
Degradation of
cholesterol to bile Salts
Free fatty acids that can
be used for ATP synthesis
- maximizes energy
production
Cholesterol to be
available for the
repair of cell
membranes
19
2
Skeletal
Muscle
 Protein
breakdown/amino
acid release
Epinephrine
2
Liver
Gluconeogenesis Glycogen Breakdown
 Blood Glucose
20
Norepinephrine stimulates beta1 receptors to cause
21
Norepinephrine stimulates beta-1
receptors to cause:
25% 25% 25% 25%
V
as
n
en
i
se
oc
D
ec
re
a
R
he
a
d
of
tio
n
tr
ic
on
s
re
le
a
rt
ra
t
...
bl
oo
ri
d
of
tr
ig
ly
e
is
ly
s
Li
po
se
e
es
1. Lipolysis of
triglyerides – beta 2
2. Vasoconstriction of
blood vessels alpha
3. Decreased heart
rate – muscarinic
receptors
4. Renin release
22
Release of Renin and ADH
(Antidiuretic Hormone)
23
Release of Renin and ADH (Antidiuretic Hormone)
• Renin is released in response to SNS stimulation of beta-1
receptors in the kidney
– Release of renin initiates renin-angiotensin-aldosterone system
(RAAS)
– Angiotensin II causes vasoconstriction leading to  Blood pressure
– Aldosterone causes increased reabsorption of water in the kidneys
causing  venous return →  cardiac output
• Aldosterone has a steroid structure, like cortisol, and is referred to as a
mineralocorticoid.
----------------------------------------------------------------------• ADH (antidiuretic hormone) is released from the posterior
pituitary in response to SNS stimulation
– ADH causes increased reabsorption of water in the kidneys
causing  venous return →  cardiac output
24
Renin
Angiotensin
Aldosterone System (RAAS)
Diagram
25
Renin
Angiotensin
Aldosterone System
(RAAS)
Diagram
Must know this!!!
Porth, 2011, Essentials of Pathophysiology, 3rd ed.,
Lippincott, p. 420.
26
Hypothalamus-Anterior Pituitary
Function
Diagram
27
Hypothalamus-Anterior Pituitary Function
Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 666
28
Hypothalamus-Anterior Pituitary
Function
Description
29
Hypothalamus-Anterior Pituitary Function
Description
• The hypothalamus and the anterior pituitary are
important in the stress response
• Cells release releasing factors that travel through
the vessels and cause cells in the anterior
pituitary to release tropic hormones
– Go to target glands to release peripheral hormones
• The hormone has a negative feedback on the anterior
pituitary and the hypothalamus to decrease the hormone
30
Feedback Inhibition
Diagram
31
Feedback
Inhibition
Diagram
Porth, Essentials of
Pathophysiology, 3rd ed.,
2011, Lippincott, p.770.
32
Peripheral Glands Controlled by the
Pituitary
Diagram
33
Peripheral Glands Controlled by the Pituitary
Porth, 2011, Essential of Pathophysiology, 3rd ed., Lippincott, p. 770
34
Regulation of Cortisol Synthesis and
Secretion
Description
35
Regulation of Cortisol Synthesis and Secretion
Description
•
•
•
•
Adrenals do not store glucocorticoids
Amount released = amount made
Regulated by negative feedback loop
Circadian rhythm
–  bedtime,  sleep, peak on awakening,  during day
• Stress increases CRH synthesis and release.
• Some of the inputs into the hypothalamus include stress and
circadian rhythms
– Also regulated by negative feedback from cortisol in the periphery
• Also acts on cells in the anterior pituitary
– ACTH circulates all over the body, such as the adrenal cortex
• Biological effects of cortisol are on nearly every body cell
• Cortisol secretion is low at night, at its highest in the morning
36
Regulation of Cortisol Synthesis and
Secretion
Diagram
37
Regulation of Cortisol Synthesis and Secretion
Lehne, 2009, Pharmacology for Nursing Care,
7th ed., Elsevier, p. 711
38
Diurnal Secretion of Cortisol
Diagram
39
Diurnal Secretion of Cortisol
Stewart, Paul, 2003, The adrenal cortex in Larson, et al, eds., Williams’ Textbook of Endocrinology, Saunders.
When we administer corticosteroids pharmacologically, we try to
mimic this diurnal rhythm.
40
Cortisol
Physiologic Effects
41
Cortisol
Physiologic Effects
•
•
•
•
•
•
Carbohydrate metabolism
Fat metabolism
Protein metabolism
Cardiovascular
Central nervous system
Stress
42
Cortisol
Carbohydrate Metabolism
43
Cortisol
Carbohydrate Metabolism
• Carbohydrate Metabolism
– Gluconeogenesis – the synthesis of new glucose
molecules in the liver
– Peripheral glucose utilization in the periphery
– Increased gluconeogenesis and decreased peripheral
glucose utilization will increase glucose levels in the
body
–  glucose uptake muscle/adipose tissue
– Promote glucose storage (glycogen)
All these make glucose more available to the brain!
44
Glucocorts
45
Glucocorts
• Supplying the brain with glucose is essential for survival.
• Glucocorts help meet this need with CHO metabolism thru the following 4
ways.
– All 4 actions increase glucose availablility during fasting and thereby ensure
the brain will not be deprived of its primary source of energy.
• When present in chronically high levels for a prolonged period of time,
glucocorts produce symptoms much like those of diabetics.
• Pro metab: promote pro breakdown.
– If present at high levels for prolonged pd of time, glucorts will cause a thinning
of skin, muscle wasting, and negative nitrogen balance
• Fat metab: glucocorts promote lipolysis (fat breakdown).
– When present at high levels for an extended time, glucocorts cause fat
redistribution, given the pt a potbelly, moon face, and buffalo hump on the
back.
46
Cortisol
Protein Metabolism
47
Cortisol
Protein Metabolism
• Promote catabolism
• Amino acids provide substrate for hepatic
gluconeogenesis
48
Cortisol
Fat Metabolism
49
Cortisol
Fat Metabolism
• Promote lipolysis
– Increases the amount of energy that is available to
the cells
• Free fatty acids provide substrate for the
Krebs cycle.
50
Cortisol
Cardiovascular System
51
Cortisol
Cardiovascular System
• Required for the integrity of the blood vessels,
including their ability to constrict
52
Cortisol
Central Nervous System
53
Cortisol
Central Nervous System
• Increases excitation
• Euphoria
• Alertness
54
Cortisol
Stress Response
55
Cortisol
Stress Response
• Stress:
– Stress increases CRH secretion by the
hypothalamus
• CRH secretion stimulates ACTH (adrenocorticotropic
hormone) secretion, which increases cortisol secretion
56
Effect of Acute Stress
57
Effect of Acute Stress
• Goals: survival, vigilance, alertness, arousal,
aggression
• Designed to be self-limiting and short term
• Similar to the “Fight” or “flight” – SNS activation –
shortest term
• Activation of the HPA (hypothalamus pituitary adrenal)
axis promotes energy utilization and availability of
substrate for tissue repair. – longer term.
– Even though this is longer term, it is not designed to be
continually activated
58
Chronic Stress
59
Chronic Stress
• Prolonged activation of the system
• Stage of exhaustion may be reached of the
system
• Health problems may result
60
Chronic Activation of the Stress
Response May Exacerbate
Diseases
61
Chronic Activation of the Stress
Response May Exacerbate Diseases
Cardiovascular
Heart disease, stroke
Immune
Autoimmune diseases
GI
Endocrine
CNS
Ulcers, irritable bowel syndrome,
colitis, vomiting, diarrhea
Diabetes mellitus, metabolic
syndrome
Fatigue, eating disorders, depression,
insomnia, post-traumatic stress
disorder
62
Coping and Adaptation
Description
63
Coping and Adaptation
Description
• Humans have the capacity to adapt and cope
with stressors based on a lot of different
things
• Very young and very old people do not
respond to stress as well as middle-aged
people
• Hardiness – the ability to go on despite
problems
• It is harder to adapt to a sudden stressor
64
Coping and Adaptation
Diagram
65
Coping and
Adaptation
Porth, 2011, Essentials of
Pathophysiology, 3rd ed., Lippincott, p.
216.
66
Coping
67
Coping
• The coping response can exaggerate or
moderate the consequences of the stress
response
• Outcome is determined by coping strategies
– Effective coping moderates stress
– Ineffective coping exacerbates stress
68
Nursing Care and Stress
69
Nursing Care and Stress
• “Nurses should put the patient in the best possible
condition for nature to restore or preserve health, to
prevent, or cure disease” (Florence Nightingale)
– This is still performed today
• Today’s hospital environment (stressful!)
– Turbulence, frenzied pace, telephones, intercoms,
electronic alarms, pagers, telemetry
– The hospital environment is not very conducive to
rest
• Is the hospital a place of healing?
70
Types of Environments
Diagrams
71
This Environment
72
Or this Environment…
73
Nurse’s Role in Dealing with
Stress
74
Nurse’s Role in Dealing with Stress
• Nurses can help patients deal with
the stress of injury, disease, or
psychological stressors
–Augment the patient’s own methods of
coping
–Provide the means for adapting to
stressors
75
Supportive Care
76
Supportive Care
• Should be given to every patient
• Maintain/restore homeostasis by monitoring fluid,
electrolytes, blood pressure, heart rate, etc., and making
necessary corrections.
• Provide adequate nutrition to provide substrate for
energy generation and repair/maintenance of tissues.
• Provide appropriate sleep-wake cycles.
– Postpone blood draws and other care
– Darken the room as far as possible
• Provide protection from stressful life events.
– Appropriate visitors
– Restful environment
– Clear explanations and patience
77
Non-Pharmacologic Methods
78
Non-Pharmacologic Methods
• Music therapy
• Relaxation techniques
• Guided imagery
• Massage therapy
• Biofeedback
79
Disorders Affecting the Stress
Response: Hypothalamic
Pituitary Adrenal Axis
80
Cushing’s Syndrome
Glucocorticoid Excess
81
Cushing’s Syndrome
Causes
82
Cushing’s Syndrome
Causes
• Primary causes
• Secondary causes
83
Cushing’s Syndrome
Primary Causes
84
Cushing’s Syndrome
Primary Causes
• Hypersecretion of ACTH by pituitary
adenomas (benign tumors) (Cushing’s disease)
• Hypersecretion of glucocorticoids by adrenal
adenomas and carcinomas
• These are rare
– Hardly ever see primary Cushing’s syndrome
85
Cushing’s Syndrome
Secondary Causes
86
Cushing’s Syndrome
Secondary Causes
• Caused by chronic administration of
pharmacologic glucocorticoids (autoimmune
diseases such as rheumatoid arthritis, organ
transplant)
• This is the most common cause of cushingoid
changes
87
Signs/symptoms of Cushing’s
Syndrome
88
Signs/symptoms of Cushing’s Syndrome
• Obesity
– Redistribution of fat to
abdomen
• Hyperglycemia/glycosuria
• Hypertension
• Fluid, electrolyte
disturbances
• Osteoporosis
• Muscle weakness
• Cataracts
• Hirsutism
• Menstrual
irregularities
• Decreased resistance
to infection because
steroids are
immunosuppressant
• Moon facies
• “Buffalo hump”
• Psychiatric changes
89
Cushing’s Syndrome
Diagram
90
Signs & Symptoms of
Cushing’s Syndrome
Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p.
695.
91
Treatment for Cushing’s
Syndrome
92
Treatment for Cushing’s Syndrome
• Primary Cushing’s syndrome - surgical removal of
diseased adrenal gland or diseased pituitary
– If bilateral adrenalectomy is required, patient will need
replacement with both glucocorticoids and
mineralocorticoids (aldosterone)
• Secondary Cushing’s syndrome
– If glucocorticoid administration is the cause, decrease
the dose as much as possible.
93
Etiology of Adrenal Insufficiency
94
Etiology of Adrenal Insufficiency
• Primary hypoadrenalism
• Secondary hypocortisolism
95
Etiology of Adrenal Insufficiency
Primary Hypoadrenalism
96
Etiology of Adrenal Insufficiency
Primary Hypoadrenalism
• Primary hypoadrenalism – Addison’s disease
– Can be contracted via infection, hemorrhage,
surgical removal of the adrenal glands
– Glucocorticoid deficiency, and possibly
mineralocorticoid (aldosterone) insufficiency
97
Etiology of Adrenal Insufficiency
Secondary Hypocorticolism
98
Etiology of Adrenal Insufficiency
Secondary Hypocortisolism
• Secondary hypocortisolism
– Abrupt discontinuation of chronic pharmacologic
glucocorticoids
• This is the most common cause of adrenal insufficiency!
– Hypopituitarism creates a deficiency in cortisol due to
insufficient ACTH secretion
• Glucocorticoid deficiency, but not mineralocorticoid
– (Aldosterone is controlled by Angiotensin II not ACTH from
the pituitary gland)
99
Regulation of Cortisol Synthesis
and Secretion
Description
100
Regulation of Cortisol Synthesis and Secretion
Description
• Pharmacologic steroids produce a negative feedback effect on the
hypothalamus and pituitary.
– CRH and ACTH are decreased to zero
– Over time, the adrenal gland becomes less able to produce cortisol.
• If pharmacologic steroids are discontinued abruptly, CRH and ACTH
will increase but the adrenal cannot respond.
– The person will be out of corticosteroids
• Can be very dangerous
• There may also be a problem with physiologic stress such as
surgery, infection, etc. – extra steroids should be given.
– Normally cortisol will increase
– If a person is on pharmacologic steroids, the adrenal gland does not know
about the stressor and cannot respond
• Will have to increase steroids because the adrenal gland cannot increase its production
of cortisol to meet the stressor
101
Regulation of Cortisol Synthesis
and Secretion
Diagram
102
Regulation of Cortisol Synthesis and Secretion
Porth, 2011, Essentials of
Pathophysiology, 3rd ed., Lippincott, p.
791.
103
Signs and Symptoms of Addison’s
Disease
104
Signs and Symptoms of Addison’s
Disease
• Glucocorticoid deficiency
– Hypoglycemia, anorexia, nausea, vomiting,
diarrhea, anxiety, depression,
hyperpigmentation
• Mineralocorticoid deficiency
– If deficiency is due to malfunctioning or absent adrenal
gland
– Fluid volume deficit, hyperkalemia,
hyponatremia, orthostatic hypotension due to
dehydration
105
Addisonian Crisis
106
Addisonian Crisis
• Major complication, life threatening
• May occur with abrupt discontinuation of
pharmacologic steroids or failure to administer
extra steroids to a steroid-dependent patient who
has additional stress (surgery, trauma).
– Severe hypotension
– Hyponatremia
– Dehydration
– Hyperkalemia
107
Treatment of Addisonian Crisis
108
Treatment of Addisonian Crisis
• Immediate replacement of cortisol with
hydrocortisone
• Hydrocortisone is fast acting and has both
glucocorticoid and mineralocorticoid activity
• May also need mineralocorticoid replacement as
well as the steroids
109
Normal secretion of cortisol from
the adrenal cortex is the
HIGHEST at
110
Normal secretion of cortisol from the
adrenal cortex is the HIGHEST at:
25%
25%
t
12
m
id
n
ig
h
pm
4:
00
n
no
o
12
A
M
8:00 am
12 noon
4:00 pm
12 midnight
8:
00
1.
2.
3.
4.
25% 25%
111
Agents for Replacement Therapy
in Adrenal Insufficiency:
112
Agents for Replacement Therapy in
Adrenal Insufficiency:
•These apply if the person has primary adrenal issues
•Glucocorticoids
•Mineralocorticoids
113
Fludrocortisone (Florinef)
114
Fludrocortisone (Florinef)
• The only drug for aldosterone replacement
– Is an aldosteorne agonist
• Aldosterone replacement, but also has some glucocorticoid
activity.
• Most of the time, is given with a glucocorticoid.
• Renal effects:
– Like aldosterone, acts on the collecting ducts to promote
Na+ reabsorption (H20 ) in exchange for K+, H+
• Cardiovascular effects (harmful effects with levels):
– Promotes myocardial remodeling and fibrosis
– Vascular fibrosis
115
Glucocorticoids
116
Glucocorticoids
• Cortisol
• Very commonly used
• Physiologic vs. pharmacologic
effects
– Physiologic = low levels for
replacement in primary
Addison’s disease
– Pharmacologic = high levels
for immunosuppression
(organ transplant) or antiinflammatory activity.
• Pharmacological steroids are
more commonly given in
large doses
Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 711
117
Oral Glucocorticoid Drugs Used
to Treat Adrenal Insufficiency
118
Oral Glucocorticoid Drugs Used to Treat
Adrenal Insufficiency
• Hydrocortisone: has some mineralocorticoid activity.
• Dexamethasone
• Prednisone
• These drugs will be discussed in detail in the section on
steroids for non-endocrine disorders.
• When used for adrenal insufficiency (steroid
replacement), doses are low to produce physiologic
levels and effects.
119
Hydrocortisone for Adrenal
Insufficiency
120
Hydrocortisone for Adrenal Insufficiency
• Replacement therapy
– Oral hydrocortisone is ideal for chronic
replacement therapy
– Parenteral administration used for acute adrenal
insufficiency and to supplement oral doses at
times of stress
– May suffice as sole therapy since it has
mineralocorticoid activity
– Dirt cheap!
121
High Dose Glucocorticoid
Therapy for Non-Endocrine
Disorders
122
High Dose Glucocorticoid Therapy for NonEndocrine Disorders
• Glucocorticoids have powerful anti-inflammatory and
immunosuppressive actions.
– These do not occur at physiologic doses but at higher,
pharmacologic doses.
• When used at high doses for their anti-inflammatory or
immunosuppressive effects, the physiologic effects are
magnified and cause important side effects.
• Non-endocrine use of glucocorticoids is much more common
than use as replacement for adrenal insufficiency.
123
Anti-inflammatory/
Immunosuppressive Effects of
Pharmacologic Doses of
Glucocorticoids
124
Anti-inflammatory/Immunosuppressive Effects
of Pharmacologic Doses of Glucocorticoids
• Inhibit synthesis of inflammatory mediators
– Prostaglandins, leukotrienes, histamine
– Reduce swelling, warmth, redness, pain
• Suppress infiltration of phagocytes
– Damage from lysosomal enzymes is averted
• Suppress proliferation of lymphocytes in response to the
immune system
– Reduce immune component of inflammation
– This could be both good and bad
125
Therapeutic Use of
Glucocorticoids in Nonendocrine
Disorders
126
Therapeutic Use of Glucocorticoids in
Nonendocrine Disorders
•
•
•
•
•
•
•
•
Rheumatoid arthritis – intra-articular or systemic
Systemic lupus erythematosus - oral
Inflammatory bowel disease - oral
Allergic conditions – topical or systemic
Asthma – inhaled or systemic
Cancer
Suppression of allograft rejection
Prevention of respiratory distress syndrome in preterm
infants (administered to the mother in threatened
preterm birth)
– Promotes fetal lung maturation
127
“Local” Administration of
Glucocorticoids
128
“Local” Administration of Glucocorticoids
• Inhalation or intra-articular
• On the skin
• Since steroids are very lipid soluble, some of the locallyadministered dose will get into the bloodstream but
concentrations will be lower than if it were administered
systemically
• Because blood levels are lower with these routes of
administration, side effects are lessened.
– Local administration is the best for avoiding side effects
129
Oral Dosing Guidelines
130
Oral Dosing Guidelines
• For chronic conditions, usually start with low dose and
increase until symptoms improve
• Daily dosing:
– Give entire dose before 9AM every morning (limits adrenal
suppression since it coincides with the normal peak level of
cortisol).
– Some patients may require a 2nd dose in the afternoon.
• Alternate day dosing:
– May be possible in some patients as the 1st step in tapering
– Reduces adrenal suppression, risk of growth retardation, overall
toxicity
131
Steroid Use for Acute Conditions
132
Steroid Use for Acute Conditions
• “Steroid pulse” is given at a high dose initially
with tapering over a week or 2-week period.
– Example: Oral prednisone, 60 mg. for 4 days, 50
mg for 2 days, 40 mg for 2 days, 30 mg. for 2 days
and so on.
• This type of regimen will not cause adrenal
suppression.
• Ex. poison ivy
133
Diurnal Secretion of Cortisol
Diagram
134
Diurnal Secretion of Cortisol
Stewart, Paul, 2003, The adrenal cortex in Larson, et al, eds., Williams’ Textbook of Endocrinology, Saunders.
When we administer corticosteroids pharmacologically, we try to
mimic this diurnal rhythm.
135
Adverse Reactions of
Pharmacologic Glucocorticoid
Therapy
136
Adverse Reactions of Pharmacologic
Glucocorticoid Therapy
• When taken chronically in large doses (non-endocrine disorders),
there are a multiplicity of adverse effects that must be monitored
and dealt with.
–
–
–
–
–
Metabolism
Bone
Fluids and electrolytes
Immune system
Eye problems
• Cataracts
• Glaucoma
– Peptic ulcers
– Growth retardation in children
– Psychiatric side effects
• Often the patient has to take a 2nd or 3rd drug to counteract the bad
effects of the steroids.
137
Glucocorticoid Therapy
Effects on Metabolism
138
Effects on Metabolism
• Intensified effects of physiologic doses
• Hyperglycemia/diabetes
– This is a significant adverse effect that frequently
results in the patient being treated for diabetes and
experiencing the long-term complications of diabetes.
• Suppression of protein synthesis
• Fat deposits mobilized and redistributed (cushingoid
habitus)
• Osteoporosis
139
Glucocorticoid Therapy
Effects on Bones: Osteoporosis
140
Glucocorticoid Therapy
Effects on Bones: Osteoporosis
Glucocorticoids cause bone loss by:
• Suppression of bone formation by osteoblasts
• Acceleration of bone resorption by osteoclasts
• Reduction of intestinal absorption of calcium
141
Osteoporosis
142
Osteoporosis
• Osteoporosis with resultant fractures is a
frequent, serious complication of therapy
• Ribs and vertebrae most affected
• More likely to occur with systemic therapy (as
opposed to inhaled or intra-articular uses)
143
Osteoporosis
Prevention
144
Osteoporosis
Prevention
• Bone mineral density test prior to treatment
• Use routes of administration that do not result in high blood
levels (topical, inhalation, or intra-articular).
• Patients should receive calcium and vitamin D supplements
• Bisphosphate therapy (alendronate, etidronate) preserves bone
by inhibiting osteoclastic bone resorption.
– Although these drugs are approved for glucocorticoid-induced
osteoporosis, they are not approved for osteoporosis prophylaxis.
• Calcitonin inhibits osteoclasts – this drug is also not approved
for osteoporosis prophylaxis.
145
Glucocorticoid Effects on Fluid
and Electrolytes
146
Glucocorticoid Effects on Fluid and
Electrolytes
• Retention of water and sodium may result in
hypertension and edema
• Hypokalemia can lead to dysrhythmias
• Precautions:
– Consider restricting sodium intake
– Consider adding potassium rich foods to diet, or
administration of supplements
– Monitor BP
• Instruct patient to notify practitioner of fluid retention
and palpitations (a sensation of rapid heart beat).
147
Glucocorticoid Effects on
Immune System Infection
148
Glucocorticoid Effects on Immune System
Infection
• Immunosuppressant
• Suppression of immune system increases susceptibility to
infection:
-New infection or reactivation of latent infection (TB)
• Steroids prevent the inflammatory manifestations of
infection such that fulminant infection may develop without
detection.
– The person may not develop a fever, redness, swelling, pain, etc.
• Prevention and close monitoring are key
– Pneumocystis carinii pneumonia common, therefore
sulfamethoxazol/trimethoprim prophylaxis is
recommended
149
Glucocorticoid Treatment and
Myopathy
150
Glucocorticoid Treatment and
Myopathy
• Manifests as muscle weakness
• Muscles of arms and legs affected most
• Damage may prevent ambulation
• If myopathy develops, dosage should be
reduced
151
Glucocorticoids and the
Development of Cataracts and
Glaucoma
152
Glucocorticoids and the Development of
Cataracts and Glaucoma
• Extremely common complication
• Cataracts are a common complication of long term
therapy:
– Eye examination every six months
– Advise patient to contact provider with changes in
vision
• Oral glucocorticoids can cause glaucoma:
– Usually develops rapidly, reverses within 2 weeks of
cessation
• However, the person should taper the dose
153
Glucocorticoids and Peptic Ulcer
Disease
154
Glucocorticoids and Peptic Ulcer Disease
• Glucocorticoids inhibit prostaglandin synthesis,
augment secretion of gastric acid and pepsin, inhibit
production of protective mucus, reduce gastric mucosal
blood flow → GI ulceration
• Risk increases with other ulcerogenic drugs, such as
NSAIDS
• Early detection crucial through examination for occult
blood in the stool
• Instruct patient to notify practitioner if stools become
black (melana)
155
Glucocorticoids and Growth
Retardation in Children
156
Glucocorticoids and Growth Retardation in
Children
• Probably as result of reduced DNA synthesis,
decreased cell division
• Assess height and weight regularly
• Growth suppression may be minimized with
alternate day therapy
157
Glucocorticoids and Psychiatric
Side Effects
158
Glucocorticoids and Psychiatric Side
Effects
• Most people experience increased
alertness, energy, etc.
• Psychosis with hallucinations, mood
changes, and other psychological
disturbances is unusual.
159
Long Term Corticosteroid
Therapy
160
Long Term Corticosteroid Therapy
• Bypasses negative feedback loop and results in gradual loss
of adrenal and pituitary hormone reserves; atrophy of
ACTH secreting cell occurs.
• Sudden withdrawal results in acute adrenal insufficiency:
the most common cause of adrenal insufficiency.
– Could be fatal
• Patients on glucocorticoids greater than 2 weeks have some
degree of HPA suppression.
• Secondary adrenal insufficiency is prevented by gradual
“weaning” the patient from these drugs over weeks to
months.
161
Regulation of Cortisol Synthesis
and Secretion
Description
162
•
Regulation of Cortisol Synthesis
and Secretion
Description
Pharmacologic steroids produce a negative feedback effect on
the hypothalamus and pituitary.
– CRH and ACTH are decreased.
– Over time, the adrenal gland becomes less able to produce cortisol.
• If pharmacologic steroids are discontinued abruptly, CRH and
ACTH will increase but the adrenal can’t respond.
• There may also be a problem with physiologic stress such as
surgery, infection, etc. – extra steroids should be given.
• Have adrenal insufficiency because of negative feedback
mechanism on pituitary and hypothalamus and adrenal gland
cannot respond to CRH and ACTH
163
Regulation of Cortisol Synthesis
and Secretion
Diagram
164
Regulation of Cortisol Synthesis and Secretion
Porth, 2011, Essentials of
Pathophysiology, 3rd ed., Lippincott, p.
791.
165
Glucocorticoid Withdrawal
166
Glucocorticoid Withdrawal
• Should be done slowly (“taper”)
• Schedule is determined by degree of adrenal
suppression
• Strategies for weaning
• Depending on the time the person has been on steroids
and the dose used, the tapering period may be years or
they may never be able to be completely weaned.
167
Strategies for Weaning People off
of Glucocorticoids
168
Strategies for Weaning People off
of Glucocorticoids
•
•
•
•
•
Multiple daily doses to single daily dose
Institute alternate day dosing
Taper gradually over months
Continue to monitor, adjust dose
Increase dose for major stressors, such as
surgery
• Even if steroids are discontinued, the patient
may need supplementation in the event of a
major stressor because the adrenal gland may
be inadquate
169
Adrenal Suppression and
Physiologic Stress
170
Adrenal Suppression and Physiologic
Stress
• Patient taking glucocorticoids long term
require increased doses at times of stress
• Patients should carry an identification to
inform emergency personnel
• Patients should always have emergency supply
of glucocorticoids on hand
171
Pregnancy and Lactation
172
Pregnancy and Lactation
• Use of steroids in pregnancy should be carefully
weighed.
– Animal studies show increased birth defects; no studies in
humans.
– Discontinuation of steroids could be serious for the mother in
terms of re-exacerbation of a disease, rejection of an organ,
adrenal insufficiency, etc.
• Adrenal hypoplasia with adrenal insufficiency is a
possibility in the infant due to the action of the steroids
• Large doses over long term in a lactating woman could
cause growth retardation or other adverse events in the
baby
– If these are necessary, perhaps the mother should not breast
feed.
173
Preparations
174
Preparations
• The half-life, mineralocorticoid potency (aldosterone
activation), and glucocorticoid potency are important
variables (Table 71.1 in Lehne).
• Long-acting steroids (betamethasone and
dexamethasone) are more potent than
hydrocortisone.
• Depot preparations are available for intra-articular
and intramuscular injection (Table 71.2 in Lehne).
175
Integrative Body Functions II:
Alterations in Temperature
Regulation
176
Body Temperature Regulation
177
Body Temperature Regulation
• Core body temp maintained
• 36-37.5C (97-99.5 F)
• Individual differences, diurnal variations
• Lowest in the morning and then
increases
• Maximum body temperature is
around 6pm
178
Normal Diurnal Variations in
Body Temperature
Diagram
179
Normal Diurnal Variations in Body Temperature
Porth, 2011, Essentials of
Pathophysiology, 3rd ed.,
Lippincott, p. 65.
180
Thermoregulatory Center
181
Thermoregulatory Center
• Core body temp is regulated by the thermoregulatory
center in hypothalamus.
• The center receives input from cold and warm thermal
receptors located throughout body and generates output
responses that conserve body heat or increase
dissipation.
• Thermostatic set point is set so body core temperature is
maintained within normal limits:
– With increased temperature, heat-dissipating
behaviors are stimulated
– With decreased temperature, heat-producing
182
behaviors are stimulated
Responses to Conserve Heat
183
Responses to Conserve Heat
• Vasoconstriction of superficial blood vessels
reduces heat loss from the skin into the
environment.
• Contraction of piloerector muscles that
surround hairs on skin – if we had fur, it would
be fluffed up to conserve heat.
• Assumption of huddle position to conserve
heat
184
Responses to Produce Heat
185
Responses to Produce Heat
• Shivering – muscle movement produces heat
• Increased production of epinephrine which increases the
availability of glucose and free fatty acids for fuel.
– As we burn fuel, we generate heat
• Increased production of thyroid hormone, which increases
metabolism.
186
Responses to Decrease Heat
187
Responses to Decrease Heat
• Dilation of the superficial blood vessels
– “Flushing” of skin and dissipation of heat
– Transfer of heat to the body surface where it is lost through
convection or radiation
• Sweating – produces loss of heat through evaporation
– Controlled by the SNS
– Evaporative heat losses are dependent on ambient temperature
and humidity
– In temperatures greater than body temperature, evaporative
heat loss is essential for control of body temperature.
188
Mechanisms of Fever
Description
189
Mechanisms of Fever
Description
• The pyrogens cause the resetting of the
thermostatic set point
– Released by the inflammatory response
– The set point is set to a higher level and the
temperature-raising responses are initiated
190
Mechanisms of Fever
Diagram
191
Mechanisms of Fever
Porth, 2011, Essentials of
Pathophysiology, 3rd ed.,
Lippincott, p. 68.
192
Fever Mechanisms
193
Fever Mechanisms
• Elevation in body temperature that is caused by a
cytokine-induced upward displacement of the set
point of the hypothalamic thermoregulatory
center.
• Caused by a number of microorganisms and
substances, “exogenous pyrogens”
• Exogenous pyrogens induce host cells to produce
fever-producing mediators, “endogenous
pyrogens”
– Interleukins, Prostaglandin E
194
Core Temperatures
195
Core Temperatures
• Greater than 41C (105.8F) or less than 34C
(93.2F) indicate the normal thermoregulation
is impaired
196
Elevations of Temperature
197
Elevations of Temperature
• Fever (pyrexia)
• Hyperthermia
• Neurogenic fever
198
Elevations of Temperature
Fever
199
Elevations of Temperature
Fever
• Upward displacement of hypothalamic set
point
• Usually caused by inflammatory mediators like
IL-1 or by bacterial products
• In children over 6 mos or so and
immunocompetent adults, we would expect
to see a temperature of over about 100°F
(37.8°C).
200
Elevations of Temperature
Hyperthermia
201
Elevations of Temperature
Hyperthermia
• Set point is unchanged (unlike in fever when the set
point is changed)
– The mechanisms that control body temperature are
ineffective in maintaining temperature within normal
range when heat production may be excessive or when
there is exposure to high ambient temperatures
– Ex. status epilepticus, ambient temperatures are extremely
high
202
Elevations of Temperature
Neurogenic Fever
203
Elevations of Temperature
Neurogenic Fever
• Neurogenic Fever: Origin in CNS, caused by damage
to hypothalamus; resistant to anti-pyretics
– Seen in stroke or brain-injury patients
204
Caution Related to Temperature
Changes
205
Caution Related to Temperature
Changes
• Certain individuals may not be able to mount a fullblown fever response! Therefore, we have to be
careful in our evaluations of temperature
elevations in these people.
– Infants, especially newborns.
– Immunosuppressed individuals
• Chemotherapy
• Organ transplant
• HIV infection
– Frail elderly
206
Purpose of Fever
207
Purpose of Fever
• May not be harmful and may be helpful
• “Cook” the poisons?
• May enhance immune function
• Inhibit microbial growth
• If it is a low fever and the person is functioning
fairly well, it is okay not to lower it immediately
208
Patterns of Fever
209
Patterns of Fever
• Intermittent
• Remittent
• Sustained
• Relapsing
210
Patterns of Fever
Intermittent
211
Patterns of Fever
Intermittent
• Temp returns to normal every 24 hours
• Seen in children a lot
212
Patterns of Fever
Remittent
213
Patterns of Fever
Remittent
• Temp does not return to normal and varies a few
degrees in either direction
214
Patterns of Fever
Sustained
215
Patterns of Fever
Sustained
• Temp remains above normal with minimal variation.
216
Patterns of Fever
Relapsing
217
Patterns of Fever
Relapsing
• One or more episodes of fever, each as long as
several days, with one or more days of normal
temps between.
• Ex. malaria
218
Physiologic Behaviors of Fever
219
Physiologic Behaviors of Fever
Set
point --->
Chill
Actual temp->
Plateau Defervescence
Flush
Chill
Pre-dromal
Defervescence
Time
• RR,  HR, Sweating
• metabolic rate,  need for 02, use of
body proteins for energy, metabolic acidosis
•Headache
•Changes in mentation
220
Treatment of Fever
221
Treatment of Fever
• Fever is a manifestation of disease state,
important to determine cause
• Treat infection, condition causing fever
• Modify environment
• Support hypermetabolic state
• Protect vulnerable organs
222
Anti-pyretics
223
Anti-pyretics
• Aspirin, acetaminophen
– Aspirin should not be used to treat fever in
children!
– Acetaminophen or ibuprofen would be the drugs of
choice
• Anti-pyretics alleviate discomforts and protect
vulnerable organs
• Anti-pyretics reset the hypothalamic
temperature control center to a lower level by
blocking activity of COX-2, thereby inhibiting
pyrogen-induced synthesis of prostaglandins.
224
Heat Exhaustion
225
Heat Exhaustion
• Heat exhaustion: related to loss of salt and water
through the sweat.
– Temp between 37.8 and 40°C but not terribly
elevated
– May be exhausted, sweating profusely
– Treat with cooling, rehydration
226
Heat Stroke
227
Heat Stroke
• Heat stroke: Severe life threatening failure of
thermoregulatory mechanisms resulting in an
excessive rise in body temp (> 40C, 104 F), absence
of sweating, and loss of consciousness.
– Common in elderly in non-air conditioned
settings.
– Also seen in military/police settings during
excessive physical training on hot days.
228
Hypothermia
229
Hypothermia
• Core temps less than 35C (93F)
– Accidental: Environment
– Controlled: Surgery
• Lower the person’s metabolic rate in order to protect
themselves
• Those at risk for accidental hypothermia:
– Infants, elderly, malnourished,
alcohol/sedatives, hypothyroidism
– Hikers, swimmers
230
Manifestations of Hypothermia
231
Manifestations of Hypothermia
• Changes in mentation, poor coordination, slurred
speech.
• Intense shivering with mild hypothermia, but shivering
decreases as hypothermia becomes more severe.
• Vasoconstriction of surface vessels – pale, even blue.
• Cold diuresis
• Dehydration and elevated hematocrit (Hct) (increases
viscosity)
• In moderate to severe hypothermia, metabolic rate
decreases significantly (this is why hypothermia is used
in surgery).
232
Treatment of Hypothermia
233
Treatment of Hypothermia
• Re-warming:
– Passive: Remove the person from the cold
environment, cover with blankets, warm fluids to
drink, etc.
– Active: Immerse in warm water, use a heating pad
(careful!). When hiking/camping, get in a sleeping
bag naked with another (warm) naked person.
– Active core re-warming: heated fluids into the GI
tract or peritoneal cavity, extracorporeal rewarming of blood.
234
Which of the following alters the
hypothalamic temperature setpoint?
235
Which of the following alters the
hypothalamic temperature set-point?
l
or
tis
o
C
rm
ia
yp
o
H
rt
he
r
yp
e
H
th
e
m
ia
ve
r
Fever
Hyperthermia
Hypothermia
Cortisol
Fe
1.
2.
3.
4.
25% 25% 25% 25%
236
Integrative Functions III
Thyroid
237
Thyroid Hormones
Description
238
Thyroid Hormones
Description
• Thyroid hormone comes in two types
– Triiodothyronine
– Thyroxine
• Get there using the amino acid tyrosine
– Add iodine to create monoiodotryrosine and then
add another iodine to create di and then hitch
together a mono and a di to create T3 or two di to
create T4
239
Thyroid Hormones
Diagram
240
Guyton & Hall, Textbook of Medical Physiology, 10th ed., 2000, Saunders, p. 860.
241
Thyroid Hormones
Description
242
Thyroid Hormones
Description
• Hormones are synthesized in cells in the ducts
• The duct is not empty, but rather is filled with
colloid (or thyroid globulin)
– When the T3 and T4 have been synthesized they
secrete them into the duct, where are hitched to
the
243
Thyroid Hormones
Diagram
244
245
Porth, 2011, Essential of Pathophysiology,
3rd
ed., Lippincott, p. 783
Thyroid Hormone Receptors
Description
246
Thyroid Hormone Receptors
Description
• Most body cells have thyroid receptors
• The thyroid hormone receptor is a nuclear receptor that influences gene
transcription.
• Only T3 binds to the thyroid receptor – T4 must be converted to T3 inside
the target cells before it will activate the receptor.
• T3 and T4 are synthesized by the thyroid and are synthesized
• Thyroid receptor that is activated by T3 influences the transcription of
multiple genes, so it has multiple effects in many different cell types.
• Thyroid receptor is a nuclear receptor, leading to synthesis to the proteins
with a plethora of effects
247
Thyroid Hormone Receptors
Diagram
248
249
Thyroid Hormone Effects
250
Thyroid Hormone Effects
•
•
•
•
•
•
Regulates cell breakdown
Stimulates metabolic rate
Growth and development
Cardiovascular system
Gastrointestinal system
Central nervous system
251
Thyroid Hormone Effects
Regulation of Cell Breakdown
252
Thyroid Hormone Effects
Regulation of Cell Breakdown
• Thyroid hormone regulates protein, fat, and
carbohydrate breakdown in all cells.
•
1.
•
2.
•
3.
•
4.
Stimulates fat breakdown and
release of free fatty acids.
Decreases cholesterol and
triglycerides.
Stimulates carbohydrate
metabolism.
Stimulates protein breakdown.
253
Thyroid Hormone Effects
Stimulation of Metabolic Rate
254
Thyroid Hormone Effects
Stimulation of Metabolic Rate
• Thyroid hormone stimulates the metabolic
rate.
•
1.
•
•
2.
3.
Increases respiratory rate and
oxygen utilization.
Stimulates body heat production.
Decreases body weight.
255
Thyroid Hormone Effects
Cardiovascular System
256
Thyroid Hormone Effects
Cardiovascular System
• Thyroid hormone affects the cardiovascular
system.
1. Increases blood flow and cardiac output.
2. Increases heart rate.
3. Increases the cardiac contractility.
257
Thyroid Hormone Effects
Growth and Development
258
Thyroid Hormone Effects
Growth and Development
• Thyroid hormone is important in growth and
development.
1. Promotes CNS development in utero
2. Stimulates growth hormone secretion and skeletal
maturation
- Previously women who were hypothyroidic gave
birth to babies who were mentally retarded
(cretins)
259
Thyroid Hormone Effects
GI Tract
260
Thyroid Hormone Effects
GI Tract
• Thyroid hormone affects the GI tract.
1. Increases GI motility.
2. Increases secretion of digestive juices.
261
Thyroid Hormone Effects
Central Nervous System
262
Thyroid Hormone Effects
Central Nervous System
• Thyroid hormone affects the CNS
1. Increases the speed of impulse conduction
(can be estimated from deep tendon
reflexes).
2. Increases neuronal activity in the CNS.
263
Hypothalamic-Pituitary-Thyroid
Feedback
264
HypothalamicPituitary-Thyroid
Feedback
Porth, 2011, Essential of Pathophysiology, 3rd ed., Lippincott,
p.
265
784
Considerable Lag Time Built into
the Thyroid System
266
Considerable Lag Time Built into the Thyroid System
Guyton & Hall, Textbook of Medical Physiology, 10th ed., 2000, Saunders, p. 861.
267
Both Hypo- and HyperThyroidism Come on Slowly and
Have Vague, Systemic Symptoms
268
Both Hypo- and Hyper- Thyroidism Come
on Slowly and Have Vague, Systemic
Symptoms
•Patients may not notice how severe the symptoms have
become because they come on slowly
•Caregivers may diagnose depression or a viral illness
rather than thyroid disease.
•Because it has systemic effects and is insidious
•The thyroid may or may not be enlarged.
269
Screening for Thyroid Disease
270
Screening for Thyroid Disease
•The TSH level is the accepted screening test.
•If TSH is high or low, tests for T3 and T4 are obtained.
•The diagnosis of hypo- or hyper- thyroidism is based
on the combination of the TSH, T3 and T4 levels.
•The practitioner must differentiate between a problem
in the thyroid and a problem in the pituitary.
271
Primary Hypo or Hyper
Thyroidism
272
Primary Hypo or Hyper Thyroidism
• The thyroid is not following the directions of the pituitary
but rather is acting autonomously
• Hypothyroidism --- TSH is high (saying that T3 and T4 are
low so need to make more so TSH is high) but T3 and T4 are
low.
• Hyperthyroidism --- TSH is low (pituitary says that there is
too much T3 and T4 but the thyroid makes more anyway)
but T3 and T4 are high.
• In either case, the problem is in the thyroid. The pituitary is
normal.
273
Secondary Hypo- or HyperThyroidism
274
Secondary Hypo- or Hyper- Thyroidism
• The thyroid is doing what it is told by the pituitary but
the pituitary is giving it the wrong directions
• Hypothyroid --- TSH is low and T3 and T4 are also low.
• Hyperthyroid --- TSH is high and T3 and T4 are also high.
• In either case, the problem is in the pituitary. The thyroid
is normal.
• The pituitary is telling the thyroid the wrong thing
275
Pituitary Cause for Hypo- or
Hyper- Thyroidism is Rare
276
Pituitary Cause for Hypo- or HyperThyroidism is Rare
• Secondary hypothyroidism or hyperthyroidism is rare
• Increased secretion of TSH by the pituitary is most
commonly caused by a tumor that secretes TSH.
• Decreased secretion of TSH by the pituitary could be
caused by a tumor that does not secrete TSH and crowds
out the TSH-producing cells.
• Head trauma can cause ischemia or necrosis of the pituitary
--- this might cause panhypopituitarism, a loss of all
pituitary hormones.
See “Interesting Articles section of “Course Documents” in Blackboard .
277
Common Cause of Hypo- or
Hyper-Thyroidism
278
Common Cause of Hypo- or HyperThyroidism
• Hypo- or Hyper- Thyroidism is most often caused
by problems in the thyroid (primary hypo- or
hyper- thyroidism)
• Hypothyroidism is treated by thyroid hormone
replacement therapy.
• Hyperthyroidism is treated by ablation (getting
rid of the thyroid) --- either surgical or with
radioiodine
279
A patient's TSH is low and his/her
T3 and T4 are high. What is
wrong?
280
A patient's TSH is low and his/her T3 and
T4 are high. What is wrong?
1. Hypothyroidism, pituitary
cause
2. Hyperthyroidism, pituitary
cause
3. Hypothyroidism, thyroid
cause
4. Hyperthyroidism, thyroid
cause
ro
id
is
.
H
yp
er
th
y
oi
d
ot
hy
r
yp
H
..
is
m
...
..
ro
id
is
.
er
th
y
yp
H
H
yp
ot
hy
r
oi
d
is
m
...
25% 25% 25% 25%
281
Thyroid Replacement Therapy
282
Thyroid Replacement Therapy
•TSH levels are tested about 6 weeks after therapy has
begun.
•This must be done because of the lag time following
the administration of the hormone
•TSH levels should have fallen to normal. If not, the
dose is increased and a TSH level obtained 6 weeks later.
•“Normal” TSH levels are under debate. One clinic uses
1.3 μU/ml as the target level (Lehne gives 0.3-6 μU/ml
as the normal range).
283
Thyroid Supplementation Drugs
284
Thyroid Supplementation Drugs
Thyroid supplementation drugs
T3 (liothyronine sodium)
Cytomel, Triostat
T4 (levothyroxine sodium) Synthroid, Levoxyl,
Levothroid, generic
T3 and T4 (liotrix)
Thyrolar
T3 and T4 (thyroid
extract)
Various (rarely prescribed
for newly diagnosed pts.)
285
Thyroid Replacement Therapy
Preferred Replacement Drugs
286
Thyroid Replacement Therapy
Preferred Replacement Drugs
• Pharmacodynamically speaking, all thyroid
replacement preparations will result in elevation of
T3 levels and amelioration of the hypothyroid state,
but there are pharmacokinetic reasons to pick one
replacement over another.
• T4 is preferred because of its longer half-life.
– Blood levels of thyroid hormone are more
constant with T4 therapy, even if a dose is missed.
– T4 is converted to T3 in the target cell.
287
Treatment of Hyperthyroidism
Introduction
288
Treatment of Hyperthyroidism
Introduction
• Radioiodine, medical management, or surgical
ablation.
• Either may destroy too much or all of the gland and
make the patient hypothyroid.
• In this case, thyroid replacement would be given
289
Treatment of Hyperthyroidism
Surgery
290
Treatment of Hyperthyroidism
Surgery
• While the patient is waiting for thyroid ablation, they must be
given drugs that relieve symptoms.
• This is necessary because the person does not do well in
treatment if they are hyperthyroidic
• If surgical ablation is planned, a euthyroid state should be
achieved prior to operation to prevent the development of
intraoperative thyroid storm.
291
Treatment of Hyperthyroidism
Medications
292
Treatment of Hyperthyroidism
Medications
• Beta blockers can be used to block
tremulousness, tachycardia, and anxiety.
• Calcium channel blockers can be used to
control heart rate.
293
Drug Treatment of
Hyperthyroidism
294
Drug Treatment of Hyperthyroidism
Drugs that affect the thyroid gland or thyroid hormone.
Drug
Block thyroid
hormone
synthesis?
Block peripheral
conversion of T4
to T3?
Propylthiouracil
(PTU)
yes
yes
Methimazole
yes
no
295
Preferred Drug Treatment of
Hyperthyroidism
296
Preferred Drug Treatment of
Hyperthyroidism
• Methimazole is usually preferred because of
its longer half-life and because PTU
sometimes causes very severe liver toxicity.
• In some cases, especially thyroid storm, PTU
would be preferred because of its ability to
block the conversion of T4 to T3.
297
Which of the following
medications blocks peripheral
conversion of T4 to T3?
298
Which of the following medications blocks
peripheral conversion of T4 to T3?
25% 25% 25% 25%
di
u
m
iu
m
in
e
ne
so
so
d
ol
e
ro
x
th
y
vo
Le
Li
ot
hy
r
on
i
et
hi
m
az
M
yl
th
io
ur
ac
il
Propylthiouracil
Methimazole
Liothyronine sodium
Levothyroxine sodium
Pr
op
1.
2.
3.
4.
299
Thyroid Storm
Thyrotoxic Crisis
300
Thyroid Storm
Thyrotoxic Crisis
• Sudden worsening of hyperthyroidism due to
increased release of thyroid hormones.
• Symptoms such as tachycardia, cardiac failure,
uncontrolled fever and delirium are of most
concern.
• As for hyperthyroidism, treatment consists of
agents to block release of thyroid hormone, βblockers and/or calcium channel blockers to
control heart rate, and supportive care.
301
Treatment for Thyroid Storm
302
Treatment for Thyroid Storm
1. Iodide may be given, which impairs release of
thyroid hormone from the gland. Iodide is also
given preoperatively in surgical ablation to prevent
intraoperative thyroid storm.
2. Steroids are commonly given.
– (Steroids also inhibit the conversion of T4 to T3)
303