ENDOCRINE SYSTEM - ANATOMY AND PHYSIOLOGY

ENDOCRINE SYSTEM; A
REVIEW OF ANATOMY
AND PHYSIOLOGY
BY: ROMMEL LUIS C. ISRAEL III

THE CLASSICAL ENDOCRINE SYSTEM
• Pineal gland
• Hypothalamus / Pituitary
• Thyroid
• Parathyroid
• Thymus
• Adrenal glands
• Pancreas
• Gonads
3

OTHER ENDOCRINE ORGANS
• Stomach - releases gastrin from G-cells
• Duodenum – CCK, secretin
• Heart – ANP
• Kidney – renin, erythropoietin
• Placenta - hCG
4

ENDOCRINE
SYSTEM
FUNCTION
• Maintenance of homeostasis through negative
feedback loops
5

ENDOCRINE SYSTEM FUNCTION
• Communication between organ systems within
the body (like nervous system)
• Differs from the nervous system:
• changes take longer to occur
• and changes persist longer as well.
6

ENDOCRINE SYSTEM FUNCTION
• Hormones are utilized as chemical messengers
• Messages are received by target cells
7

HORMONES
• Recall the distinction between exocrine
and endocrine glands
• Exocrine: through a duct
• Endocrine: into the blood
8

HORMONES
• Endocrine hormones are transmitted in the
bloodstream to all parts of the body
• Hormones only have an effect on those cells that
have a hormone receptor embedded in the cell
membrane (target cells)
• 2 types of endocrine hormones:
• steroid & non-steroid
9

HORMONES
Steroid Non-steroid
-Derived from cholesterol (lipid)
-Lipid soluble –passes through cell
membrane to directly cause a change in
DNA within the nucleus (activates a gene)
-Slower, longer lasting effect than non-steroid
hormones
Derived form cholesterol
Lipid soluble, need to be transported in the
bloodstream combined with a transport
proteinMainly from the adrenal cortex and/or
gonads
Mineralocoritcoid → aldosterone
Glucocorticoids → cortisol, cortisone
Sex steroids → progestin, estrogen
-Derived from an amino acid
-Hormone is 1st messenger
-Membrane receptor alters protein inside
the cell, which serves as the 2nd messenger
to alter metabolism of the cell
-Water soluble – most are transported freely in the
blood
Cascade of reactions within the cell “amplifies” the
signal
This type of hormone causes a more rapid onset
and shorter duration of the effect than steroid
hormonesTypes of Non-steroid hormones
Protein (polypeptide) – insulin, growth ho
Glycoprotein – LH, TS
Oligopeptide – ADH, oxytocin
Amine –norepinephrine, epinephrine,
10

MECHANISM OF HORMONE
ACTION
• Hormones produce their effects on target
tissues by binding to specific proteins called
hormone receptors located in the target tissues
only.
• Hormone receptors present on the cell
membrane of the target cells are called
membrane-bound receptors and the receptors
present inside the target cell are called
intracellular receptors, mostly nuclear receptors
(present in the nucleus).
11

ACTION
• Binding of a hormone to its receptor leads to
the formation of a hormone-receptor complex
• Each receptor is specific to one hormone only
and hence receptors are specific.
12

ACTION
• Hormone-Receptor complex formation leads to
certain biochemical changes in the target tissue.
• Target tissue metabolism and hence
physiological functions are regulated by
hormones.
13

HORMONES
14

SECOND MESSENGER
• ACTION OF MEMBRANE BOUND RECEPTORS
Hormones which interact with membrane-bound
receptors normally do not enter the target cell, but
generate second messengers (e.g., cyclic AMP, IP3,
Ca++ etc) which in turn regulate cellular metabolism .
• ACTION OF NUCLEAR RECEPTORS Hormones which
interact with intracellular receptors (e.g., steroid
hormones, iodothyronines, etc.) mostly regulate gene
expression orchromosome function by the interaction
of hormone-receptor complex with the genome.
Cumulative biochemical actions result in physiological
and developmental effects .
•
15

HYPOTHALAMUS
• the hypothalamus is the basal part of diencephalon,
forebrain.
• These hormones regulate the synthesis and secretion of
pituitary hormones.
• However, the hormones produced by hypothalamus
are of two types, the releasing hormones (which
stimulate secretion of pituitary hormones) and the
inhibiting hormones (which inhibit secretions of
pituitary hormones).
16

HYPOTHALAMUS
For example
• hypothalamic hormone called Gonadotrophin releasing hormone (GnRH)
• stimulates the pituitary synthesis and release of gonadotrophins.
• On the other hand, somatostatin from the hypothalamus inhibits the
release of
• growth hormone from the pituitary.
• These hormones originating in the hypothlamic neurons, pass through
axons and are released from their
• nerve endings.
• These hormones reach the pituitary gland through a portal circulatory
system and regulate the functions of the anterior pituitary.
• The posterior pituitary is under the direct neural regulation of the
hypothalamus
17

ANTERIOR
PITUITARY
• The releasing hormone is secreted into a portal system
• Cells in the anterior pituitary are stimulated to secrete another
hormone
18

POSTERIOR PITUITARY
• Neurons from the
hypothalamus enter
the posterior
pituitary and
stimulate cells to
secrete hormones
19

PITUITARY
• Interacts with many (not all) endocrine glands as part of a
feedback loop between the hypothalamus and the respective
gland.
20

PITUITARY
• The pituitary serves as a link between the CNS
(hypothalamus) and the rest of the endocrine system
21

PITUITARY
• The pituitary is suspended from a stalk (infundibulum) attached to
the hypothalamus and enclosed within the sella turcica (sphenoid
bone)
22

PITUITARY
• Actually 2 separate glands: anterior pituitary & posterior
pituitary
• No blood brain barrier in the hypothalamus
23

ANTERIOR PITUITARY
hypothalamus
(releasing
hormones)
GHRH PRF TRH CRH GnRH
pituitary
(tropic
hormones)
GH PRL TSH ACTH FSH/LH
end organ muscle,bone
adipose
mammary
gl.
thyroid adrenal
cortex
ovary &
testes
Note:
1. GH is also called somatotropin
2. There are also inhibitory factors from the hypothalamus
for GH and PRL
24

POSTERIOR PITUITARY
ADH anti-diuretic hormone, causes kidney to retain
water
Oxytocin contraction of smooth muscle
(uterus/childbirth & mammary gland ducts)
* failure of the posterior pituitary to secrete ADH
results in Diabetes Insipidus (DI)……if no ADH is
produced the result is production of LARGE volumes of
dilute urine
25

GROWTH HORMONE
• GHRH/somatostatin  GH or somatotropin  cells related
to body growth
• Produced in the ant. Pituitary
• Secretion declines gradually with age
• Many more GH producing cells in ant. pituitary than any
other type
26

GROWTH HORMONE
• Increased cell division (mitosis) & increased
cell growth & differentiation
• The main effects are on cartilage, muscle,
bone, fat
• Promotes protein synthesis
(transcription/translation)
• Anti-insulin effect - elevates blood sugar
27

GROWTH HORMONE
• Catabolism of fat for energy instead
of glucose
• Muscle & bone are effected indirectly
through Insulin like Growth Factor
(IGF-1)
• increased muscle mass, bone
lengthening and decreased fat tissue
28

GROWTH HORMONE
• Continued secretion of high levels after epiphysial plate closure
is called acromegaly
• Bones continue to thicken even after epiphysial plate closure
29

GROWTH HORMONE
• Acromegaly is usually related to a
pituitary tumor
30

PROLACTIN
• In women
• increased levels during pregnancy
• after delivery causes mammary glands
to produce milk
• In men
• increases sensitivity to LH and indirectly
enhances testosterone production
31

THYROID
GLAND
• TRH (hypothalamus) → TSH (pituitary) → Thyroid hormone
(Thyroid gland)
32

THYROID GLAND
• 2 lobes, on either
side of the trachea,
connected by an
isthmus
33

THYROID GLAND
Microscopic anatomy
• Thyroid follicles, lined by
secretory epithelium
(follicular cells)
• Filled with thyroglobulin
(transport protein)
• Parafollicular cells between
the follicles
34

THYROID
FUNCTION
• Secretes two hormones
(both require iodine as a
precursor)
• Thyroxine (T4) & Triiodothyronine (T3)
35

THYROID FUNCTION
• (T4): 90% of all Thyroid
hormone
• Less active
• Converted to T3 in the cell
• Most remains in the
bloodstream as reservoir of
thyroid hormone
36

THYROID FUNCTION
• (T3): 5 times more
metabolically active,
but only 10% of total
hormone that is
produced
37

THYROID
FUNCTION
1.Mitochondria: increased cellular respiration
2.Ribosomes: increased protein synthesis
3.Chromatin: increased transcription DNA to mRNA
• Binds to three
sites in the cell
38

HYPERTHYROIDISM
• Thyroid hormones promote cellular respiration
• Cellular respiration requires oxygen, therefore
heart rate & respiratory rate are increased
• Produces heat; causes sweating
• Higher metabolic rate requires more calories,
which is a stimulus for hunger
39

GRAVES DISEASE
• The most common form of
hyperthyroidism (autoimmune)
• Signs and symptoms may
include heat intolerance, 
appetite, weight loss, warm
moist skin, nervousness, tremor,
 BP, tachycardia, goiter,
exophthalmos
Exophthalmos may be due
to an autoimmune,
inflammatory reaction in
the soft tissue that is
confined within the boney
orbit
40

ENDEMIC
GOITER
• A goiter is an enlarged thyroid gland
• Endemic goiter is due to lack of iodine in
the diet
• No thyroid hormone is produced so there is
no negative feedback
• The thyroid gland hypertrophies as it “tries”
to make more thyroid hormone
41

HYPOTHYROIDISM
• In children (cretinism)
• permanent mental retardation due to
inadequate nervous system development
• In adults
• common cause of fatigue
• other symptoms are related to low BMR
• cold intolerance, weight gain,  CNS function
(mentation), BP, dry skin
42

PARATHYROID
GLANDS
• Not linked to the hypothalamic-pituitary axis
• 4 small nodules of tissue in the thyroid gland
43

PARATHYROID GLANDS
• PTH is secreted in response to low serum Ca++
(hypocalcemia)
1. Promotes synthesis of calcitrol (active
metabolite of vitamin D), which ↑ GI absorption
of Ca++
2. Limits Ca++ secretion by the kidney
3. Stimulates osteoclasts to reabsorb bone
44

PARATHYROIDS
• In humans, four parathyroid glands are present
on the back side of the thyroid gland, one pair
each in the two lobes of the thyroid gland
• The parathyroid glands secrete a peptide
hormone called parathyroid hormone (PTH).
The secretion of PTH is regulated by the
circulating levels of calcium ions.
45

PARATHYROIDS
• Parathyroid hormone (PTH) increases the Ca2+ levels in
the blood. PTH acts on bones and stimulates the
process of bone resorption
(dissolution/demineralisation).
• PTH also stimulates reabsorption of Ca2+ by the renal
tubules and increases Ca2+ absorption from the
digested food. It is, thus clear that PTH is a
hypercalcemic hormone, i.e., it increases the blood
Ca2+ levels.
• Along with TCT(THYROID CALCITONIN) it plays a
significant role in calcium balance in the body.
46

• PTH is opposed by the action of
calcitonin
• Secreted in response to elevated
Ca++ (hypercalcemia) by
parafollicular (C-cells) of the
thyroid gland
• Little effect in adults
• Stimulates mineral deposition in
bone by osteoblasts
Parathyroid
Glands
47

ADRENAL
GLANDS
• Each gland is
actually 2 separate
glands: the cortex
& medulla
48

ADRENAL FUNCTIONS
49

ADRENAL MEDULLA
• Secretes Catecholamines
• (Epinephrine & Norepinephrine)
• Derived from SNS neurons (Chromaffin cells) that lack dendrites
& axons
50

CATECHOLAMINES
• Adrenaline and noradrenaline are called catecholamines
which are rapidly secreted in response to stress of any
kind and during emergency situations and are called
emergency hormones or hormones of Fight or Flight.
• These hormones increase alertness, pupilary dilation,
piloerection (raising of hairs), sweating etc. Both the
hormones increase the heart beat, the strength of heart
contraction and the rate of respiration.
51

CATECHOLAMINES
• Catecholamines also stimulate the breakdown
of glycogen resulting in an increased
concentration of glucose in blood. In addition,
they also stimulate the breakdown of lipids and
proteins.
52

ADRENAL MEDULLA
• Innervated by Symphatetic Nervous System
• Secretes SNS neurotransmitters mostly
Epinephrine (Adrenalin)
• The presence of these neurotransmitters in the
circulation lowers the threshold for transmission of
an impulse in the SNS for about 30 min.
53

EPINEPHRINE
• Elevates blood sugar – glucose sparing effects to
preserve glucose for the CNS
• glycogenolysis
• gluconeogenesis
54

ADRENAL CORTEX
3 layers
55

Zona
Glomerulosa
mineralocorticoids Aldosterone:
renal Na+ & water
reabsorption
Zona
Fasciculata
gluccorticoids Cortisol
Zona
Reticularis
sex steroids Androgen,
Estrogen
ADRENAL CORTEX
56

GLUCOCORTICIODS
• Glucocorticoids stimulate, gluconeogenesis, lipolysis
and proteolysis; and inhibit cellular uptake and
utilisation of amino acids.
• Cortisol is also involved in maintaining the cardio-
vascular system as well as the kidney functions.
• Glucocorticoids, particularly cortisol, produces anti-
inflamatory reactions and suppresses the immune
response.
• Cortisol stimulates the RBC production.
57

GLUCOCORTICIODS
• ldosterone acts mainly at the renal tubules and
stimulates the reabsorption of Na+ and water and
excretion of K+ and phosphate ions. Thus, aldosterone
helps in the maintenance of electrolytes, body fluid
volume, osmotic pressure and blood pressure.
• Small amounts of androgenic steroids are also secreted
by the adrenal cortex which play a role in the growth of
axial hair, pubic hair and facial hair during puberty
58

• Aldosterone – Na+ retention/ K+ secretion
• Water follows Sodium, so fluid volume and
BP increase too
• Recall that aldosterone secretion can be
promoted by:
1. ACTH
2. Angiotensin II
3. Low Na+
4. High K+
Adrenal Cortex: Z. Glomerulosa
59

Secretes Cortisol (hydrocortisone)
• Corticosterone and cortisone are two other
similar hormones that are secreted
• Steroid medication can suppress adrenal
function
Adrenal Cortex: Z. Fasciculata
60

Two basic effects of Cortisol:
1. Glucose sparing effects: increased glucose
synthesis & protein/lipid catabolism
(gluconeogenesis)
2. Anti-inflammatory effects: inhibits WBC
function, decreased phagocytosis, decreased
chemotaxis, decreased mast cell degranulation
Adrenal Cortex: Z. Fasciculata
61

ADRENAL CORTEX: Z. RETICULARIS
• Sex steroids – small amount of estrogens & weak
androgens (DHEA), which is a precursor of
testosterone
• Testosterone is required in men & women – pubic
& axillary hair, libido, apocrine sweat glands
• most testosterone is produced in testes in men
• 50% produced by the adrenal gland in women
62

CUSHING’S
DISEASE
• Hyperfunction of the Adrenal glands
• Disrupts normal carbohydrate & protein
metabolism (Cortisol)
• characteristic lipid deposits in the face
• Potential electrolyte imbalance
(Aldosterone)
• Mood changes (Testosterone)
63

GONADS
Ovaries
• Secrete estrogen &
progesterone during the
menstrual cycle
• FSH from the pituitary
causes maturation of the
follicle & egg
• LH causes ovulation (rupture
of the follicle – release of
the egg)
Testes
• FSH promotes spermatogenesis
• LH causes interstitial cells to
secrete testosterone
• Testosterone from adrenal gland
is also present in women, but at
much lower levels
• Produces secondary sexual
characteristics in men
64

• PTH is opposed by the action of
calcitonin
• Secreted in response to elevated
Ca++ (hypercalcemia) by
parafollicular (C-cells) of the
thyroid gland
• Little effect in adults
• Stimulates mineral deposition in
bone by osteoblasts
Parathyroid
Glands
65

PANCREAS
• Not linked to hypothalamic pituitary axis
• Both exocrine & endocrine functions
66

PANCREAS
• Endocrine hormones: insulin & glucagon secreted by cells in
the islets of Langerhans
67

GLUCAGON
Alpha cells secrete glucagon
• Glucagon is secreted in response to low blood
sugar, causing glycogen to be converted to
glucose (glycogenolysis)
68

GLUCAGON
• Glucagon is a peptide hormone, and plays an
important role in maintaining the normal blood
glucose levels.
• Glucagon acts mainly on the liver cells
(hepatocytes) and stimulates glycogenolysis
resulting in an increased blood sugar
(hyperglycemia).
69

GLUCAGON
• In addition, this hormone stimulates the
process of gluconeogenesis which also
contributes to hyperglycemia.
• Glucagon reduces the cellular glucose uptake
and utilisation. Thus, glucagon is a
hyperglycemic hormone.
70

INSULIN
• Beta cells secrete insulin
• insulin is secreted in response to ↑ blood sugar, causes ↑
permeability of cell membranes throughout the body to glucose
• Except
CNS...does not
require insulin
to take up
glucose
71

INSULIN
• Insulin is a peptide hormone, which plays a major role
in the regulation of glucose homeostasis
• Insulin acts mainly on hepatocytes and adipocytes (cells
of adipose tissue), and enhances cellular glucose uptake
and utilisation.
• As a result, there is a rapid movement of glucose from
blood to hepatocytes and adipocytes resulting in
decreased blood glucose levels (hypoglycemia).
72

INSULIN
• Insulin also stimulates conversion of glucose to
glycogen (glycogenesis) in the target cells.
• The glucose homeostasis in blood is thus
maintained jointly by the two – insulin and
glucagons
73

DIABETES MELLITUS
• Elevated blood sugar
• Normal fasting blood sugar is 70 – 100 mg/dL
• 100 – 125 mg/dL is “prediabetic”
• Higher than 125 mg/dL is either Type I or Type II
diabetes
74

TYPE I DIABETES MELLITUS
• A failure of beta cells to produce insulin
• Also called IDDM (Insulin Dependent DM)
• complete loss of insulin means that replacement is required
• Usually onset is in childhood (juvenile onset)
75

TYPE I DIABETES MELLITUS
• Abrupt onset of symptoms
• DKA (diabetic ketoacidosis)
• No glucose is available to cells
• They utilize lipids instead
• This produces ketoacids (lower the pH)
• Polydipsia (thirst)
• Polyphagia (hunger)
• Polyuria (osmotic diuresis)
76

• The renal threshold for glucose resorption is exceeded
resulting in glycosuria
• Poorly controlled DM is a disease of small blood vessels
• diabetic nephropathy
• diabetic retinopathy
• diabetic neuropathy
• changes in coronary & peripheral vessels increase the
risk of vascular disease
Type I Diabetes Mellitus
77

DIABETES MELLITUS TYPE II
• An insensitivity of an insulin receptor in cell
membranes to insulin
• NIDDM (Non Insulin Dependent DM)
• usually does not require insulin (oral
hypoglycemics)
• Usually onset is as an adult
• Onset is insidious
• Usually no ketoacidosis
78

DIABETES MELLITUS
• Long term monitoring of blood sugar levels
(months)
• Hgb A1C (glycosylated hemoglobin)
• A type of hgb that incorporates a sugar molecule
• More Hgb A1C is made when blood sugar levels
are high
79

PINEAL GLAND
• The main hormone is
melatonin
• The precursor is a CNS
neurotransmitter,
serotonin
80

PINEAL
GLAND
• Production and secretion of melatonin is stimulated by
darkness
• Information about light levels is provided through the retina in
mammals
81

PINEAL GLAND
• The pineal gland is located on the dorsal side of
forebrain.
• Pineal secretes a hormone called melatonin.
• Melatonin plays a very important role in the
regulationof a 24-hour (diurnal) rhythm of our
body.
• For example, it helps in maintaining the normal
rhythms of sleep-wake cycle, body temperature.
• In addition, melatonin also influences metabolism,
pigmentation,the menstrual cycle as well as our
defense capability.
82

PINEAL GLAND
• Circadian rhythm Regulates sleep / wake cycle
• Undergoes involution during childhood, which may bring
about the onset of puberty
• Near the skin in non-mammal vertebrates
• Light levels are perceived directly
• Regulates seasonal behavior in other animals
• Migratory patterns in birds
• Breeding cycles in animals with seasonal reproductive patterns
83

THYMUS
• Posterior to the
sternum
• Larger in adolescence
• Regresses at puberty
• Secretes thymosin
84

THYMUS
• The thymus gland is a lobular structure located
on the dorsal side of the heart and the aorta.
• The thymus plays a major role in the
development of the immune system.
• This gland secretes the peptide hormones
called thymosins.
85

THYMUS
• Thymosins play a major role in the differentiation of T-
lymphocytes, which provide cell-mediated
immunity.
• thymosins also promote production of antibodies to
provide humoral immunity.
• Thymus is degenerated in old individuals resulting in a
decreased production of thymosins. As a result, the
immune responses of old persons become weak.
86

THYMUS
• Thymosin causes undifferentiated lymphocytes to become T cells
• Blood – thymus barrier in the cortex
• Only T cells that are “self tolerant” are released to the medulla and
into the rest of the body
cortex
medulla
87

TESTIS
• The Leydig cells or interstitial cells, which are present in
the intertubular spacesproduce a group of hormones
called androgens mainly testosterone.
• Androgens regulate the development, maturation and
functions of the male accessory sex organs like
epididymis, vas deferens, seminal vesicles, prostate
gland, urethra etc.
88

TESTIS
• These hormones stimulate muscular growth, growth of facial and
axillary hair, aggressiveness, low pitch of voice etc.
•
• Androgens play a major stimulatory role in the process of
spermatogenesis (formation of spermatozoa).
• Androgens act on the central neural system and influence the male
sexual behaviour (libido).
•
• These hormones produce anabolic (synthetic) effects on protein
and carbohydrate metabolism.
89

OVARY
• Females have a pair of ovaries which produce two
groups of steroid hormones called estrogen and
progesterone.
• Ovary is composed of ovarian follicles and stromal
tissues. The estrogen is synthesised and secreted mainly
by the growing ovarian follicles.
• After ovulation, the ruptured follicle is converted to a
structure called corpus luteum, which secretes mainly
progesterone.
90

OVARY
• Estrogens produce wide ranging actions such as
stimulation of growth and activities of female
secondary sex organs, development of growing ovarian
follicles, appearance of female secondary sex characters
(e.g., high pitch of voice, etc.), mammary gland
development. Estrogens also regulate female sexual
behaviour.
• Progesterone supports pregnancy. Progesterone also
acts on the mammary glands and stimulates the
formation of alveoli (sac-like structures which store
milk) and milk secretion.
91

ANF (ATRIAL NATRIURETIC
FACTOR)
• hormones are also secreted by some tissues which
are not endocrine glands.
For example
• the atrial wall of our heart secretes a very
important peptide hormone called atrial natriuretic
factor (ANF),which decreases blood pressure.
• When blood pressure is increased, ANF is secreted
which causes dilation of the blood vessels. This
reduces the blood pressure.
92

OTHER HORMONES
• The juxtaglomerular cells of kidney produce a peptide hormone
called erythropoietin which stimulates erythropoiesis (formation of
RBC).
• Endocrine cells present in different parts of the gastro-intestinal
tract secrete four major peptide hormones, namely gastrin,
secretin,
• cholecystokinin (CCK) and gastric inhibitory peptide (GIP).
• Gastrin acts on the gastric glands and stimulates the secretion of
hydrochloric acid and pepsinogen.
• Secretin acts on the exocrine pancreas and stimulates secretion of
water and bicarbonate ions.
• CCK acts on both pancreas and gall bladder and stimulates the
secretion of pancreatic enzymes and bile juice, respectively.
• GIP inhibits gastric secretion and motility
93

TYPES OF HORMONES
On the basis of their chemical nature, hormones can be
divided into groups :
• (i) peptide, polypeptide, protein hormones (e.g., insulin,
glucagon,pituitary hormones, hypothalamic hormones, etc.)
• (ii) steroids (e.g., cortisol, testosterone, estradiol and
progesterone)
• (iii) iodothyronines (thyroid hormones)
• (iv) amino-acid derivatives (e.g., epinephrine).
94

TYPES OF HORMONES
On the basis of their chemical nature, hormones can be divided into
groups :
• (i) peptide, polypeptide, protein hormones (e.g., insulin,
glucagon,pituitary hormones, hypothalamic hormones, etc.)
• (ii) steroids (e.g., cortisol, testosterone, estradiol and progesterone)
• (iii) iodothyronines (thyroid hormones)
• (iv) amino-acid derivatives (e.g., epinephrine).
95

STRESS
• A stressor is a stimulus to promote a response to a threatening
situation
physical stress - an actual
physical change
psychological stress
 post surgical
 hot/cold
 trauma
 malnutrition
 hemorrhage
 originates in the
cerebral cortex
 abstraction about a
potentially harmful
situation
 anger, grief,
depression, anxiety, guilt
96

STRESS
3 phases of the stress response
1. The alarm phase
2. Resistance phase: occurs as glycogen is
consumed
3. Exhaustion phase: chronic stress occurs over
a period of weeks
97

• An immediate response
• Increased sympathetic output (fight or flight)
• The adrenal medulla secretes catecholamines like
adrenalin (SNS neurotransmitter)
Stress: The Alarm Phase
98

Sympathetic Nervous System input to the kidney
initiates the Right Artery Aneurysm cascade which
leads to :
• Increased BP to supply large skeletal muscles
• Increased fluid retention to compensate for
potential fluid loss through sweat or
hemorrhage
• Glycogen stores are consumed in a few hours
Stress: The Alarm Phase
99

Occurs as glycogen is consumed:
• Hypothalamus → CRH →
ACTH → Cortisol
Stress:
The Resistance
Phase
100

• Cortisol decreases glucose use peripherally
(glucose sparing for the CNS)
• Promotes the breakdown of protein & fatty
acids, which are converted to glucose in the liver
(gluconeogenesis)
Stress: The Resistance Phase
101

• Both Adrenaline (alarm phase) and Cortisol (resistance
phase) elevate blood sugar
Stress and Blood Sugar
102

STRESS: THE EXHAUSTION PHASE
Chronic stress occurs over a period of weeks:
• Less protein is available for immune system function
(gluconeogenesis)
• ↓ ability to make antibodies (protein)
• ↑ susceptibility to infections
• ↓ protein available for wound healing
103

PARACRINE SECRETIONS
• Paracrine hormones exert a
local effect
• Eicosanoids are paracrine
secretions
• They are produced by the
Arachidonic acid pathway
104

• Arachidonic acid (a fatty
acid) is produced from
phospholipids in the cell
membrane
• This reaction is catalyzed
by phospholipase A2
Arachidonic Acid Pathway
105

Arachidonic acid is then
subjected to either of two
metabolic pathways
1. lipoxygenase – leads to
the production of
leukotrienes, chemical
mediators of
inflammation
106

2. cyclooxygenase –
leads to the
production of
prostaglandins,
thromboxane, and
prostacyclin
107

Thromboxane is secreted by platelets to enhance
platelet aggregation
Prostaglandins have many effects depending upon
the specific metabolite
• fever
• pain
• etc.
108

• Steroid medication (e.g.
cortisol/prednisone) blocks
the production of
arachidonic acid
(phosphlipase)
• *Non-steroidal anti-inflammatories (NSAID’s)
like aspirin and Ibuprofen block the
cyclooxygenase pathway to reduce
inflammation & fever
109

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