Adrenal Cortex Physiology

Dr. Carina C. Gomez, February 21, 2017

Suprarenal – the adrenal glands are structures above the

kidneys.
Adrenal – adrenal glands adjacent to kidney.
Each adrenal gland weighs around 4 grams.
2 MAJOR DIVISIONS
Adrenal Medulla
o Inner part, 10-20%
o comprised of neurons that migrate from
neuroectodermal tissue to the abdominal cavity where
they are enclosed within the adrenal cortex that are
trapped inside (Neuroectodermal).
o The neurons lose their axons and become secretory cells,
secreting neurotransmitters directly into the blood, thus
are also considered hormones. (mediates
Neuroendocrine signaling)
o This includes the catecholamines primarily epinephrine
80%, norepinephrine 20% & dopamine in small amount.
Adrenal Cortex
o Outer part, 80-90%
o Mesodermal origin.
o These are secreting cells (not neurons).
o 3 major hormones are secreted here (corticosteroids)
these include: mineralocorticoids – prototype substance
is aldosterone; glucocorticoids – cortisol; androgens –
prototype substance is DHEA dehydroepiandrosterone.
*Although these are known as adrenal gland, these are 2 different
structures.
* 3 zones of the adrenal cortex, acronym = (G.F.R)
Zona glomerulosa, Zona fasciculata, Zona reticularis
*In the Zona reticularis DHEA is produced initially then it is
converted into testosterone & estrogen.

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 Blood Supply
o from the aorta, renal and phrenic arteries
o Direction of blood flow from these vessels should always be
from the adrenal cortex to the medulla.
Why?
o Well because of the enzyme phenylethanolamine-N-
methyl transferase (PNMT) that converts norepinephrine
(NE) to epinephrine (E) (Dra. says a slightly different name
in the recording so I double checked on google! - ;))
o primarily found in the cortex of the adrenal gland
(although some books claim it can be found in other
organs).
o Blood flow from the cortex to the medulla will wash
out PNMT into the medulla where it is needed. Another acronym by Dra. (GFRSSS) – Glomerulosa, fasciculata,
o Conversion of NE to E is cortisol dependent. reticularis, salt, sugar, sex!
Layers of Adrenal Cortex Steroids are referred to as wonder drugs because they treat
many illnesses however they have massive side effects.

Adrenal Regulation

Zona Glomerulosa
o outermost layer
o 15% of the adrenal cortex.
o The only layer capable of secreting mineralocorticoid in the
form of aldosterone due to presence of aldosterone
synthase which is absent in other layers.
o Secretes substances important in salt metabolism. Regulation of adrenal cortex secretion is mainly via Negative
Zona Fasciculata Feedback.
o thickest layer o The initiating stimulus is always opposite the response;
o 75% of the adrenal cortex. ↑initiating stimulus ↓response.
o Secretes glucocorticoids in the form of cortisol & also Negative feedback is not always inhibitory. It can also be
corticosteroids. Androgen secretion also occurs but in stimulatory.
lesser amounts.
o Secretions important for sugar (glucose) metabolism. ↑Cortisol, ↑androgen = inhibitory effect to hypothalamus &
Zona Reticularis pituitary (ACTH dependent hormones).
o thinnest layer ↑Aldosterone has no inhibitory effect on hypothalamus &
o 10% of the adrenal cortex. pituitary because aldosterone is ACTH independent. It is
o Primarily secretes androgen in the form of DHEA which is regulated by RAAS. (ACTH increases Aldosterone, but
converted to testosterone & estrogen. Also secretes Aldosterone will not give feedback)
glucocorticoid but in lesser amounts.
o Secretions important for sex.

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What are the stimuli for adrenocortical hormone secretion? :
STRESS! Any type of stress, running, jogging, emotions, surgery,
hot weather, fever, psychosis, burns, lab manuals.
Sometimes on admission to hospital, blood sugar is high but this
does not mean one has diabetes. (That’s why Dra. resigned from
her many chairman positions, to avoid stress. And she will not be
stressed by us, rather, we should be the one to be stressed ;) )
Stress activates the paraventricular nuclei to secrete CRH →
which acts on anterior pituitary (corticotropes) to release POMC
(Proopiomelanocortin – large structure with an N-Carboxy
terminal) → which is cleaved, one of the fragments is ACTH →
acts on adrenal cortex increasing secretion of aldosterone,
cortisol, androgen.
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Beta lipoproteins – substances with opioid-like action, pain
suppressing agents, analgesia system in the body.
4 steps in pain transmission;
 Transduction
 Transmission
 Perception
 Pain modulation – this step is affected by beta
lipoproteins or endorphins (endogenous opioid
peptide).
MSH – secreted from the intermediate lobe in lower animals,
activates melanocytes in melanopores to cause skin
pigmentation.
*Humans have no MSH because we do not have intermediate
lobe we have no melanocortin activated by ACTH.
Pathways:
Zona Glomerulosa – Mineralocorticoid Pathway
And so on…
 All of them come from CHOLESTEROL (that is why they are
called steroid hormones)
 Rate-Limiting Step – Conversion of Cholesterol to
Pregnenolone (will not be converted back)
 After conversion, it will now depend on what enzyme is
present on that layer to determine the path it will take.
 CORTISOL SECRETION
 PRIMARILY Negative feedback : Hypothalamic-
Pituitary Axis (CRH-ACTH axis)
 Circadian rhythm – ↑morning ↓evening
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 ANDROGEN SECRETION Effect of ACTH on Adrenal Cortical Cells
 Hypothalamic-Pituitary Axis (CRH-ACTH Axis) CRH  ACTH  will bind either to Adrenocortical cells (Binds
 Cortical Androgen-Stimulating Hormone with Melanocortin 2 Receptor, MC2R) or the skin (MC1R - will
 Cortisol has a greater effect on HPA than androgen, cause skin pigmentation)
both are ACTH dependent hormones.
 Also Developmental pattern of secretion Binding with MC2R  Effects:
Immediate: Production of Hormones (Aldosterone, Cortisol,
 ALDOSTERONE SECRETION Androgen) by activating all enzymes needed
 ECF Potassium Ion Concentration ( K+) Subsequent/Intermediate:  Enzyme/Protein Synthesis and 
(Major mechanism regulating aldosterone) Gene Transcription (p450 dependent – occurs in mitochondria)
Hyperkalemia - activates aldosterone secretion thus
Long-Term: structural changes in adrenal cortex
increasing K secretion.
Hypokalemia – Inhibits aldosterone secretion,  Hypertrophy – Size and functional complexity of organelles
decreasing K secretion.  Hyperplasia – size and number of cells
 Renin-Angiotensin-Aldosterone System (AII)
Angiotensin II
 ECF Sodium Ion Concentration ( Na+)
Minor mechanism
 Hypothalamic-Pituitary Axis (ACTH)
(has little effect on controlling the rate of secretion)

The Suprachiasmatic Nuclei in the hypothalamus controls the

Highest secretion of cortisol is at 8 in the morning, lowest at 8 in
set point of various body activities.
the evening – circadian rhythm.
 Thirst – controlled by ventrolateral hypothalamus
 Satiety – controlled by ventromedial hypothalamus
 Temperature (hot) – controlled by anterior hypothalamus
 Temperature (cold) – controlled by posterior
hypothalamus
 Endocrine function – supraoptic, paraventricular, arcuate

For Adrenal Cortex - PARAVENTRICULAR

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Stimuli for release of renin;
 Low arterial blood pressure/hypotension
 low ECF volume/dehydration
 low total blood volume
 low renal blood flow/hypoperfusion
 increased sympathetic discharge *Starts with Cholesterol  Pregnenolone (ACTH Dependent –
= these will activate JG cells in afferent & efferent arterioles to Rate-Limiting Step)
*Angiotensin II (facilitates conversion of corticosterone to
secrete renin  acts on angiotensinogen from the liver
converting it into angiotensin 1  converted to angiotensin 2 by Hydroxycorticosterone, thus, increasing Aldosterone Production
ACE in the lungs, angiotensin 3,4,5,6,7,8 are produced by *Blockage of a pathway will lead to increase production of other
steroids (blockage of androgen, increase aldosterone and cortisol
aminopeptidases in the blood… all are vasoconstrictors, 
production.
increase total peripheral resistance  increasing blood pressure
to corrected initiating stimuli.
Angiotensin 2,3,4,5,6,7,8 are all potent stimulators causing the
adrenal cortex to secrete aldosterone which ↑Na reabsorption, ↑
K secretion

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Major source of cholesterol is LDL (80%) circulating in the blood
→ binds with LDL receptor → enters the cell (can also be
synthesized within the cell from acetyl CoA) → stored or
esterified (cholesterol esters are formed if hormone is not
needed immediately), hydrolysis occurs if hormones are needed
→ cholesterol enters the mitochondria (because conversion of
cholesterol to pregnenolone is P450 dependent) this process is
ACTH dependent → pregnenolone leaves the mitochondria &
enters smooth ER → converted to progesterone, 17-OH-
progesterone, 11-deoxycortisol (non P450 dependent reactions
in smooth ER) → 11-deoxycortisol returns to the mitochondria to
be converted to cortisol (P450 dependent) thus mitochondria
release cortisol. (Refer to endocrine system diagram above!)
Cimetidine – anti-ulcer drug, P450 inhibitor.
*Aldosterone and Cortisol, if present in the blood, can easily
enter the cell. Its receptor is present in the cytoplasm.
*At the start, the receptor is bind to an inhibitory protein
(chaperone). When aldosterone is present, the inhibitory protein
dissociates. You now form Mineralocorticoid-Aldosterone
Complex  enter the nucleus  act on gene (Same with Cortisol)
*Steroid hormones are not usually stored in the cell unlike
proteins, polypeptides & catecholamines which are stored.
 Cortisol is not stored appreciably in the adrenocortical
cells. Hence, an acute need for increased amounts of
circulating cortisol requires rapid activation by ACTH.
 In women, the adrenal glands ultimately supply 50 –
60% of the androgenic hormone requirements. That is
why androgen levels are low in women, so no
masculinizing effects.
In males additional androgen are produced by the testes.
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MINERALOCORTICOIDS
 Regulation of Salt
 Aldosterone - principal mineralocorticoid
o accounts for about 90%
o 60% (protein-bound usually inactive), 40% (free form
usually active)
o Half-life – 20 minutes (longer half-life because it is
protein-bound, unlike in insulin which is in free form)
o destroyed mainly in the liver (bile/feces, 25%), mainly
excreted in the urine
 mainly affect electrolytes (minerals K+/Na+) of the ECF.
When you change sodium concentration, water follows.
Thus, its main purpose is to regulate ECF Volume and ABP
 Deoxycorticosterone, Corticosterone, Cortisone, Cortisol and
9α Fluorocortisol (synthetic). These substances have
mineralocorticoid activity. Why is cortisol included here? It
is a glucocorticoid with mineralocorticoid activity.
ALDOSTERONE
 Mineralocorticoid
 Maintain BP, water, and salt balance
 Help kidney retain sodium and excrete potassium
 Functions to maintain blood volume and stabilize BP. – One
involved in CVS Long term control
(Familiarize yourself with the diagram above ↑)
*Aminopeptidases in the blood will convert Ang II to Ang III, IV,
and so on…
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 BIOLOGIC EFFECTS
  renal tubular reabsorption of sodium (late DCT and
primarily CD)
Late DCT is blocked by K sparing diuretics (aka aldosterone
antagonists e.g. Spironolactone which blocks aldosterone
thus Na reabsorption is inhibited which means water is not
reabsorbed = diuresis.
K sparing because K is not secreted.
Another K sparing mechanism involves ENac (epithelial Na
channel e.g. Amiloride)
Another electrolyte being secreted is hydrogen, thus one
can develop metabolic alkalosis.
  renal tubular secretion of potassium (DCT and CD)
  renal tubular secretion of hydrogen (DCT and CD)
 maintenance of ECF volume (principal function)
 same effect to sweat glands, salivary glands, intestinal
epithelial cells in colon (Sodium and Potassium Absorption)

Hyperaldosteronism

*Aldosterone & cortisol are steroids – they bind to cytoplasmic

receptors (mineralocorticoid receptors MR). These receptors are
bound to inhibitory proteins, when aldosterone binds with the
MR, the inhibitory protein dissociates forming an MR-
aldosterone complex which then enters the nucleus, to regulate
gene expression by increasing the activity of the Na/K pump.

*Na pump hypothesis - ↑Na/K pump activity → Na reabsorbed

into ECF in exchange with K this leads to ↓Na inside the cell
which favors reabsorption permeability (permeate hypothesis).
↑K in ECF favors secretion of K.

*Aldosterone also increases mitochondrial activity to produce

more ATP for the Na/K pump (metabolic hypothesis).
(Refer to image above) o Problem is in the adrenal cortex = primary
o Problem anywhere outside the adrenal cortex = secondary

The manifestation is the same in both types. So, what is the

difference between primary & secondary?

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In primary – adrenal cortex secretion of aldosterone is very BIOLOGIC EFFECTS
high, it follows a negative feedback - ↑ aldosterone ↓renin
In secondary, it could be a problem in the kidney e.g. a tumor
increasing renin secretion. Therefore ↑renin = ↑aldosterone (no
more negative feedback because the tumor will continuously
increase renin secretion)
In primary - ↑aldosterone, ↓renin
In secondary - ↑ aldosterone, ↑renin
Thus, to differentiate the two, the doctor requests for the level of
renin.

Primary Aldosteronism (Conn’s Syndrome)

 caused by a tumor of the zona glomerulosa cells or
hyperplasia of the adrenal cortices (high aldosterone
secretion, inhibit renin secretion)
 manifestation: (Hypertension and weakness – most important)
o hypokalemia
o ECFV (slight) - (muscle weakness)
o Increase plasma Na+ concentration (very slight because
there are other hormones affecting Na)
o Hypertension – (increased ECF volume &
vasoconstriction)
o muscle weakness – due to hypokalemia
GLUCOCORTICOIDS
 Cortisol (aka hydrocortisone) – principal glucocorticoid
(with mineralocorticoid activity)
 accounts for about 95% of all glucocorticoid activity
 90 - 95% (protein bound), 10 -15% (free form)
 mainly to globulin (cortisol binding globulin or
transcortin) and albumin
 half-life – 60 to 90 minutes (greater %
of protein binding = greater half-life)
 destroyed mainly in the liver (bile/feces, 25%),
mainly excreted in the urine (water soluble)
 Corticosterone, Cortisone (synthetic), Prednisone
(synthetic) most common in the market, causes high
appetite = obesity, Methyl prednisone (synthetic)
preferred option w/ lesser side effect, Dexamethasone
(synthetic) used as topical, long term corticosteroid.
CORTISOL
 Principal glucocorticoid
 increases blood glucose level
 has slight mineralocorticoid activity
 helps to resist physical, mental and other types of
stresses.
 essential for life (without it, you die!)
Thyroid hormones are not essential for life however one will
suffer from the deficiency.
When some doctors run out of ideas in treating a patient, they
administer steroids and the patient improves. Don’t do that Lol
METABOLIC EFFECTS
Carbohydrates Metabolism (Diabetogenic Effect)
 HYPERGLYCEMIC effect
 stimulates gluconeogenesis from CHON (either proteins
from the liver) - MAIN/PRIMARY effect
 decreases glucose utilization by cells because it has anti-
insulin effect (Prevents transport of glucose into the cell)
 increases:
 glucose-6-phosphatase (used in glycogenolysis)
 gluconeogenic enzymes
 critical for the survival during fasting
 “adrenal diabetes” and
  insulin secretion (Hyperinsulinemia – Same with GH)
Protein Metabolism (Catabolic/Antianabolic)
o ↑ protein catabolism and ↓ protein synthesis
o facilitate conversion of protein to glucose
o ↓ proteins in the body except liver and plasma
o increases plasma and liver proteins (thus, all the
proteins in the body will decrease except in the blood
and liver because proteins broken down will be
transported to the liver for gluconeogenesis via the
bloodstream)
Fat Metabolism (Catabolic/Antianabolic)
o (+) lipolysis (growth hormone and epinephrine) -
extremities
o (+) lipogenesis (central portion of the body)
o That is why truncal obesity is present
o (+) ketogenesis

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Permissive action
o cortisol may amplify the effect of another hormone on a
process that it does not affect directly.
o potentiates and extends the action of glucagon,
epinephrine and growth hormone (greater effect on these
hormones)
o *All of these are not direct effects of cortisol. It has
permissive action. It can only amplify the effect of other
hormone’s processes.
*COMPARED with Growth Hormone: Similar with Carbohydrate
effect, opposite with Protein effect, in fats, it depends.
Summary
Cortisol has; (when stimulated by stress)
 Diabetogenic Effect (gluconeogenesis and anti-insulin
effect)
 Lipolytic (extremities), Lipogenetic (central body
region) and Ketogenic Effect
 Proteolytic Effect
Effects on Muscle
 maintains the contractility and work performance of
skeletal and cardiac muscle (↑ Ach synthesis (skeletal) and
↑ Na+K+ ATPase and β-adrenergic receptors (cardiac) -----
normal level
 Is it beneficial for athletics to take steroids? It improves
muscle performance both skeletal and cardiac ONLY IN
NORMAL LEVELS.
  muscle mass and strength (↑ muscle catabolism and ↓
muscle protein synthesis) cortisol excess
 long term excessive intake of cortisol  will cause protein
breakdown. Muscles are mainly made up of proteins. Then
it will decrease muscle mass resulting to its weakness.
 ↓ slow oxidative type I : fast glycolytic type II-B muscle
fiber ratio
Effects on Bones
-most devastating effect of cortisol is here
  bone formation (most profound effect)
o ↓ formation of mature osteoblasts
o ↑ apoptosis of osteoblasts and osteocytes
o ↓ collagen synthesis
  bone resorption/destruction
o ↑ osteoclasts formation and mRNA of collagenase
(enzyme that destroys the organic matrix of the bone)
  Ca++ absorption in the GIT (antagonizes the effect of 1,25
(OH)2D3 and (-) its synthesis)
 PTH production(PTH removes the calcium out of the bone)
 In longer usage of steroids, you must have a prophylactic
vitamin D and Calcium
 2 components of bones: Collagen (The “steel”) and Calcium &
Phosphates (The “cement”) – PROVIDES THE TENSILE
STRENGTH
 Construction of bones – Osteoblasts
 Breakdown of Bones – Osteoclasts
 Vitamin D increases the absorption of Calcium and
Phosphates in the GIT
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Effects on Connective Tissue
 (-) collagen synthesis (thinning of the skin and walls of the
capillaries)
 leads to intracutaneous hemorrhage
 That is why when you have high levels of cortisol, you have
micro-hemorrhages, gum bleeding, massive stretch marks
 If you are using topical steroids, only apply thinly into your
skin
Osteoporosis
 Most devastating effect
 feared and sometimes devastating complication of
glucocorticoid therapy that last for more than a few
weeks.
 That is why you only give your steroids for 2 weeks, if
not, you are prone to osteoporosis
 preventive treatment with Ca++ and vitamin D and
diphosphanates that inhibits bone reabsorption is
advisable.
Effects on the Cardiovascular System
 required for the maintenance of normal blood pressure
 maintains CO by sustaining myocardial performance
  arteriolar tone (permits normal responsiveness of the
arterioles to AII, E and NE), that is why you facilitate
vasoconstriction
  production of vasodilator prostaglandin
  endothelial permeability (helps maintain the blood
volume) (One anti-inflammatory effect)
Effects on the Kidney
  glomerular filtration rate by ↓ preglomerular (afferent
arteriole) resistance and ↑ glomerular plasma flow
 ↑ free water clearance (diuresis)
 required for generation of NH3 (acid load) - buffer
 ↑ Ca++ and PO4- excretion
 Cortisol increases afferent arteriolar vasodilation 
Increase GFR  ↑ urine
Effects on the CNS
 modulates emotional tone (excitability, behavior and
mood) and wakefulness. (Type I and II GRs are present in
various areas of the brain)- In normal level
 in excess level, you either enhance the depression or
enhance the excitability. That’s why psychiatric disorders
are present with very high steroids.
 ↓ REM sleep and ↑ NREM and the time spent awake)
 The patients suffer insomnia by decreasing the REM sleep.
 ↓ the ability to detect salty taste
 (+) appetite center (↑ neuropeptide Y)
 It increases appetite especially on pregnisol not more on
methyl pregnisolone. By increasing the orexogenic
substance, neuropeptide YY which increases appetite, thus
it stimulates the appetite center.
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 insomnia, elevate or depress moods, decrease memory
function and lower the threshold for seizure activity
(psychiatric disorders) cortisol excess
 INFANTILE SPASM- a type of seizure where patients are
given steroids because they increases the threshold for
seizure activity by inflammation.
Effects on the Fetus
 The beneficial effect of steroids can be found on the fetus
because it facilitates the maturation of the CNS
 facilitates maturation of the fetus (maturation of the CNS,
retina, skin GIT and lungs - PRIMARILY)
 one of the common cause of death in premature individuals
is respiratory distress because of low level of surfactant
then steroids will increase the surfactant. The respiratory
membrane is thin, if it is thick, diffusion of oxygen is low.
Steroids make it thinner.
 ↑ synthesis of surfactant, flattening of alveolar cells,
thinning of the lung septa and ↑ the rate of dev’t of the
laveoli (last weeks of gestation)
Effects on blood cells
  eosinophils, basophils and lymphocytes by increasing
apoptosis
 Since eosinophils and basophils mediate allergy,
steroids have a powerful anti-allergic effect. It
decreases lymphocytes by increasing their apoptosis,
therefore it is an immunosuppressant.
 For patients who underwent transplant or autoimmune
disorder they are given steroids to lower their immune
system. That’s why they suffer from immunodeficiency.
 Sometimes, patients with anemia or dengue are
challenged with steroids to increase platelet. Take note
that though they are increased, it doesn’t mean they
have increased protective function.
  red blood cells, neutrophils and platelets
 For neutrophils, only the number is increased but its
function is increased.
Inhibits inflammatory responses (↓ eosinophils)
-another beneficial effect of steroids
CARDINAL SYMPTOMS OF INFLAMMATION:
Rubor- redness caused by vasodilation. steroids increases
tone
Tumor- swelling due to increase permeability. Fluid goes
to the interstitium. Steroid causes vasoconstriction, thus
decreases permeability,
Calor (heat) and Dolor (pain) caused by inflammatory
substances due to migration of inflammatory cells which is
decreased by steroids.
Therefore, all the steps of inflammation are inhibited by
steroids
Mast cells increases the inflammatory mediators when
they degranulate. This is stabilized by steroids, decreasing
their granulation.
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 stabilizes lysosomal membrane.
 decreases capillary permeability.
 decreases migration of WBC and neutrophils and
recruitment of leukocytes into the inflamed area and
phagocytosis of damaged cells.
 ↓ phagocytic and bactericidal activity of neutrophils.
 (-) differentiation and proliferation of mast cells
 ↓ proliferation of fibroblast (causes keloid) and their
synthesis and deposition of fibrils.
 If you have a keloid former, you can apply steroid
because you decreases the proliferation of fibroblast.
 suppresses febrile response to infection
 reduces the releases of interleukin-1
 thromboxane, prostaglandin, leukotrienes, nitric oxide
and PAF
 causes resolution of inflammation
 that is why you are given steroids during inflammation
Inhibits immune responses
 this is one of the substances that actually reset the set point,
causing fever
 if you have antigen and macrophage, thus, increasing your
IL-1, temperature increases. Thermostat should lower it
down by excessive sweating, hyperventilation by activating
the anterior hypothalamus. Parasympathetic is being
activated.
 If body is too cold, posterior hypothalamus is activated, and
shivering will occur normalizing the temperature.
Sympathetic is activated.
 In fever, you increase this. With steroids these are being
blocked.
 ↓ circulating T lymphocyte (T helper)
 ↓ migration to antigenic stimulation and function.
(transplant rejection)
 (-) differentiation of monocytes to macrophages
 influenced the proliferation, differentiation and
production of antibodies by the B cells. (blocked by
steroids by decreasing lymphocytes)
↓ IL-1, IL-2 and IL-6 but ↑ IL-4 (↑ IgE)
Phospholipase A that acts on arachidonic acid produces
cyclooxygenase. COX will then produce prostaglandins,
bradykinins, thromboxane which causes vasodilation. This
cascade is blocked by steroids.
Thus this is a very powerful for maturation of fetus and for anti-
inflammation.
 Again, there is decreased lymphocytes, decreased migration.
Thus, very much used in patients who had transplant to
suppress the immune system and decrease the migration of
antigenic stimulation in transplant patients.
Check the pictures below
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 Immunodeficiency
 increases the susceptibility to bacterial, fungal and viral
infection and allow their dissemination.
 Cortisol is important in resisting stresses;
 trauma of almost any type
 infection
 intense heat or cold
 injection of E and NE, necrotizing substances
 surgery
 debilitating diseases
 physical stress ex. Exercise
SUMMARY
 our body cope with these stresses with the help of steroids.
 Connective Tissue: decrease collagen synthesis. In high level-
gum bleeding, micro hemorrhages, skin thinning causing
stiae formation, tensile strength of bone
 On inflammation: decreases lymphocytes, migration, IL and
all the responses for inflammation. It also decreases capillary
permeability, stabilizes lysosomal enzymes, decreases
migration of inflammatory cells, decreases fibroblasts
proliferation.
 On the heart: increases arteriolar tone, facilitating
vasoconstriction, inhibits production of vasodilators which
increases cardiac performance. Thus, maintain cardiac
function and arterial blood pressure.
 Fetus: maturation of CNS, retina, GIT, skin, primary in the
lungs concomitantly increasing the surfactant.
 Kidney: diuresis, increases water clearance due to increase
GFR, increase renal blood flow because of afferent arteriolar
dilatation
 It modulates emotional tone. Either elevate or decreased
 Sleep duration decreased (↑ NREM ↓REM)
 Appetite increase
 On muscle: maintains performance, but since it has protein it
can facilitate protein weakness
 Bone: decrease bone formation, increase bone resorption,
inhibit action of vit D, enhance action of PTH

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 Hyperadrenalism (Cushing’s Syndrome)
Cushing’s Syndrome: problem is anywhere in the body except
pituitary.
Cushing’s Disease: If it has something to do with functional
pituitary adenoma
*If you have the signs of cushing’s, we just call that cushing’s
syndrome, but if you can already pin point the problem, you call
the cushing’s disease.
Primary Hyperadrenalism
 Due to adrenal hypercortisolism (excessive secretion of
cortisol).
 Most commonly due to excessive intake of steroids. It can
also be due to
 exogenous corticosteroids
 ACTH secreting tumor ( ACTH,  Cortisol),
 functional adrenal tumor in the adrenal medulla
 functional pituitary adenoma which is called the
cushing’s disease.
 caused by adrenal cortex adenoma, bilateral adrenal cortex
hyperplasia and administration of large amount of cortisol
 PRIMARY: problem in adrenal cortex ( Cortisol,  ACTH)
 SECONDARY: problem in pituitary or hypothalamus (
ACTH,  Cortisol)
 manifested by;
 Buffalo hump hypertension (Lipogenesis at the
central)
 Moon face (Lipogenesis at the central)
 hypernatremia (Light mineralocorticoid activity)
 Truncal obesity (Lipogenesis at the central)
 hypokalemia (Light mineralocorticoid activity)
 Purplish striae (collagen inhibition)
 mild alkalosis (slight mineralocorticoid activity)
 Weakness (mainly due to protein breakdown, slightly
by hypokalemia and mineralocorticoid activity)
 vertebral fractures (due to osteoporosis)
 Osteoporosis
 easy bruisability (collagen breakdown)
 Diabetes (hyperglycemic)
 psychiatric disorders (effect on mood and behavior of
patient)
 immunodeficiency
 Secondary Hypercorticolism
  cortisol→→→  ACTH
 pituitary adenoma
 abnormal function of hypothalamus
 ectopic secretion of ACTH

*To differentiate primary to secondary based on PE, skin
hyperpigmentation occurs with secondary because of ACTH.
TRANS BY: TEAM
Hypoadrenalism (Addison’s Disease)
 due to atrophy of the adrenal cortex (autoimmunity),
tuberculous destruction and cancer invasion of the adrenal
cortex.
 *tuberculous bacilli don’t only affect your lungs, it can also
affect extrapulmonary structure like adrenal cortex.
 Because of these reasons, both glucocorticoid and
mineralocorticoid levels are decreased.
 characterized by;
 Inability to maintain normal blood glucose level
 Protohypoglycemia, but not necessarily
hypoglycemia- because you still have glucagon,
epinephrine, and norepinephrine. However, their
function is not amplified.
 Inability to cope up stress
 Depression of most metabolic functions of the body
 Skin hyperpigmentation (occurs in Secondary
Hypercoticolism and Primary hypocorticolism)
 Due to  ACTH level that binds with
melanocortex 1 receptor
 Hypotension (due to  mineralocorticoid activity)
  ECF volume shock (due to  mineralocorticoid
activity)
 hyponatremia
 hyperkalemia
 mild acidosis
 Decreased total peripheral resistance- cortisol
increases arteriolar tone and decreases
vasodilatation
 Weight loss due to decrease appetite and GI function
 Water intoxication- water moves intracellularly. If
you do not have cortisol water stays inside the cells.
 Muscle weakness- cortisol improves muscle
performance. if you have hypo and hyper cortisol,
this manifest.
 Anemia- due to its effect on RBC
 Decrease GIT motility and secretion because they are
sometimes promoted by cortisol.
 There will be no excitement here unlike in
hypercorticosolism. For hypocortisolism, there is
depression.
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 ANDROGENS
 Secreted by zona reticularis
 Dehydroepeandrosterone (DHEA) and androstenedione
- principal cortical androgens (in the peripheral circulation,
they should be converted to testosterone or estrogen
 responsible for the early development of male sex
organs.
 converted to testosterone (potent)
 “masculinizing effect”
 What will happen if there is androgen deficiency? This
will not be manifested by females and males. For males,
testis is still present to compensate.
 Excess androgen is more common for females.
 also secrete estrogen (estradiol) and progesterone
Androgenital Syndrome
AKA Virilism/hirsutism/female pseudohermaphroditism
Only in females!
 develops intense musculinizing effects throughout the body
(virilism)
 Growth of beard
 Deeper voice
 Baldness (baldness means excessive testosterone)
 Musculine hair distribution
 Growth of clitoris
 Loss of regular of menses Regression of breast tissue
(excessive testosterone will decrease your GnRH.
Without GnRH no LH surge, loss of regular menses)

Additional:
* Excessive Stress – you are prone to infection (because of
immunosuppression)
* If you will be given high dose of steroids continuously and you
abruptly stop it, you will die.
Why? Because the high level of steroids will give negative
feedback to your hypothalamus, causing low CRH and low ACTH
 cause the atrophy of the adrenal cortex.
*If there is abrupt cessation of intake, you cannot produce
cortisol (which is essential to life) because your cortex is still
atrophied.
*There should be gradual cessation of intake in dosage and in
duration (slightly increasing CRH, ACTH  reviving your adrenal
cortex)

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