Adrenal Gland Flashcards
Define the word stress? What causes stress? What cellular structure shrinks during cramming for exam sessions?
Stress- the normal physical response to events that make you feel threatened or upset your balance
Stress has evolved to help us survive
-almost anything can start stress response:
Battling traffic
-Planning a party
-Exams
Prefrontal cortex shrinks during cram sessions (but grows back after a month off).
Explain how different body parts respond to stress.
The Stress Response:
Eyes: Senses are heightened, scanning for danger, blinks become shorter (so you don’t miss what’s next)
-Skin: Stress hormones activate sweat glands in upper lip, brow, palms, pit stains
-Jaw and Hands: Muscles contract leading to chattering teeth, and shaky hands
-Mouth: The frontal lobe goes off line; you stutter or draw blanks
Stomach: Withdrawal of blood flow can lead to Knots, nausea, or butterflies.
-bladder: Energy is devoted to limbs resulting in a less competent sphincter (pee)
What does the Yerkes-Dodson Curve indicate?
The Yerkes-Dodson Curve indicates that an optimal level of stress is what we need to peform our best
When there is NOT enough stress- Unproductive
Optimal production- varies based on stress tolerance
-When there is TOO Much stress- Unproductive
performance level increases when mental arousal (stress) increases, but only up to certain point.
What occurs when stress strikes your body? What is the general adaptation syndrome? Provide examples.
When stress strikes:
your body generates specific responses (characteristic for type of stressor) or Nonspecific generalized responses (regardless of type of stressor)
General adaptation syndrome: Increases in Nervous and Hormonal responses result in state of INTENSE READINESS with FUEL Mobilized for use.
Examples of specific response to stress:
If we are cold: body shivers, skin vasoconstriction (blood vessels shrink to reduce heat loss)
if we are have an infection: increase antibody production
*Explain how stress response is coordinate by the hypothalamus. Explain what happens during short-term stress.
Stress response is coordinated by the Hypothalamus:
1. Short term stress:
Stress will stimulate the hypothalamus which will send Nerve impulses down spinal cord and stimulate the preganglionic sympathetic fibers. This will then stimulate the adrenal medulla (which secretes amino acid based hormones), and causes release of Catecholamines (Epinephrine and Norepinephrine)
Factors affected by short term stress
1. Increased Heart Rate
2. Increased blood pressure
3. Liver converts glycogen to glucose and releases glucose to blood
4. Dilation of bronchioles
5. Changes in blood flow patterns leading to decreased digestive system activity and reduced urine output
6. Increased Metabolic rate
*Explain what happens during long term stress.
Long Term Stress:
With prolonged stress, the hypothalamus will stimulate CRH (corticotropin releasing hormone) which will stimulate the corticotroph cells of anterior pituitary.
The corticotroph cells will then release ACTH (adrenocorticotropic Hormone) to target blood and enter Adrenal cortex. Adrenal cortex (secrete steroid hormone) will then stimulate release of mineralocorticoids (aldosterone) and glucocorticoids
Factors affected by Long term stress:
1. Retention of Sodium and Water by kidneys
2 . Increased blood volume and blood pressure
-Proteins and fats converted to glucose or broken down for energy
-increased blood glucose
-Suppression of immune system.
*Describe the anatomy of the Adrenal glands. What hormone does each tissue layer release? What does Adrenal medulla vs cortex composed of?
Adrenal Gland:
-Combined weight: 6-10 g: sit on top of Kidneys (like tricornered hats)
- Adrenal Cortex (80%) and Adrenal Medulla (20%)
-One of the highest Blood flow rates/g tissue (from Cortex to medulla)
Adrenal Cortex:
1. Zona Glomerulosa: makes mineralcorticoids (regulate mineral balance) Ex: ALDOSTERONE
2. Zona Fasciculata- makes glucocorticoids (regulate glucose metabolism) EX: Cortisol, Corticosterone, Cortisone
3. Zona Reticularis- makes Androgens (stimulate masculinization) Ex: Dehydroepiandrosterone (DHEA)
Adrenal Medulla- make stress hormones (stimulate sympathetic ANS (autonomic) Ex: Epinephrine and Norepinephrine
Explain the enzymatic pathway from Tyrosine to Epinephrine.
Enzymatic rxn pathway to make catecholamines from tyrosine:
1. Tyrosine undergoes sympathetic stimulation to form DOPA (tyrosine hydroxylase)
2. Dopa undergoes rxn (aa decarboxylase) to form Dopamine
3. Dopamine undergoes rxn (Dopamine Beta-hydroxylase) to form Norepinephrine
4. Norepinephrine uses cortisol to activate enzyme rxn to form Epinephrine.
Tyrosine–> DOPA–> Dopamine–>Norepinephrine–> Epinephrine
*Compare and contrast the features of the adrenal cortex and medulla. which of cortex or medulla can we live without vs Need to have?
Adrenal Cortex:
- 80% of Adrenal gland
- Makes STEROID hormones
- Embryonic origin (MESODERM)
- Innervation: nearly NONE
- Cell characteristics: Lipid Droplets
- Essential for life: YES
Adrenal Medulla: -10-20% of gland -Makes AMINE Hormones -Embryonic region: Neuroectoderm (modified post ganglionic fiber) -Innervation: SNS -Cell characteristics: Amine granules -Essential for life: NO We can live without adrenal medulla but we NEED adrenal cortex (helps us adapt to stress, maintain blood pressure and glucose)
*Describe the differential distribution of enzymes.
Cholesterol undergoes many reactions with different enzymes to eventually form Aldosterone (mineralcorticoid). ACTH stimulates different enzymes in Zona Fasciculata and Zona Reticularis of Adrenal cortex
Angiotensin II also stimulates enzyme in Zona Glomerulosa that leads to formation of aldosterone
17-alpha hydroxylase is ABSENT in Zona glomerulosa of Adrenal cortex but stimulates different enzymes to form Androgen hormones (DHEA and Androstendedione)
17-alpha hydroxylase also stimulates another enzyme to form cortisol (glucocorticoids)
Describe the regulation of Cortisol Secretion. What are the stimulatory and inhibitory factors affecting ACTH secretion?
Factors affecting ACTH (adrenocorticotropic hormone) Secretion: Stimulatory factors: -Decreased Blood cortisol levels Sleep-wake transition -stress: hypoglycemia; surgery; trauma -Psychiatric Disturbances -ADH -alpha-Adrenergic agonists -Beta-Adrenergic agonists Serotonin Inhibitory Factors: -Increased Blood cortisol levels Opioids Somatostatin
Explain the many hormones and things that ACTH stimulates. What hormones affects ACTH differently? Where is ACTH synthesized from?
- ACTH stimulates ALL steps in synthesis of cortisol, adrenal androgens, and SLIGHTLY Aldosterone
- Only CORTISOL feedbacks (ex: if high cortisol, ACTH inhibited)
- ACTH stimulates cell hyperplasia (via IGF-1)
- ACTH synthesized from a LARGE precursor, preproopiomelanocortin (POMC), which also gives rise to MSH (Melanocyte-stimulating hormone).
- Hence high ACTH levels lead to high hyperpigmentation (skin darkens)
-
What are the three main characteristics that describe cortisol secretion?
Cortisol secretion is PULSATILE, DIRURNAL, and Stimulated by Stress
Describe how cortisol secretion can be pulsatile.
Cortisol secretion can be Pulsatile (not constant): due to alternating bursts of modest cortisol secretion, separated by silent periods of little to no secretion
-the amount of cortisol secreted with each burst does NOT vary (same amount)
Frequency of secretory bursts VARY
-Reminiscent of summation; one burst adds on to previous burst.
-more frequent the stimulation, higher the level of cortisol secreted.
Explain how cortisol secretion can be Diurnal. What determines the diurnal rhythm? what alters the setting of this center (cortisol level)?
Cortisol secretion is Diurnal:
Diurnal (day-night) Rhythm: One cycle every 24 hours
-Plateau ACTH and Cortisol PEAK prior to awakening
-Lowest levels of ACTH are reached just prior to sleep
-The SUPRAHIASMATIC NUCLEUS determines this rhythm.
What alters the setting of this center?
-Lack of bright light during the day (affects circadian rhythm) or Exposure to artificial light at night (keeps steady response of cortisol
-Chronic glucocorticoids (blunts morning peak)- elevated levels of cortisol
-you have major secretions of cortisol as we are about to wake up.
Explain what happens during disruption of Circadian Rhythm. When does this usually occur? What do alternating shift workers suffer from?
Disruption of Circadian Rhythm: due to VARIABLE Work Schedule
- Takes 1 Week for body to adjust to new working hours
- Alternating shift workers suffer:
- Ulcers, Insomnia, irritability, depression, IR (infrared radiation) and Judgment is IMPAIRED
Explain the 2 scenarios that occurred due to disruption of circadian rhythm.
1979 Three Mile Island:
-4am, operators did NOT notice warning lights (were sleeping) that crucial VALVE LEFT OPEN
-Morning shift crew saw it immediately: Pipes had BURST leading to radioactive steam/water into the air
-4th costliest nuclear disaster: $11 Billion
1986 Chernobyl:
-2 engineers DEACTIVATED KEY SAFETY Systems in the early Hours violating protocol
-steam built up inside the reactor, blew the roof off the containment building causing a THICK CLOUD of radiation spread throughout Europe and the world
-Largest and costliest nuclear accident ($259 billion)
-Hence working at a certain time that is Unsuitable for clear thinking (not a good idea)
Describe how cortisol secretion is stimulated by stresses.
Stress:
Stress enhances activity of the CRH-ACTH system
(corticotropic releasing Hormone-ACTH)
- it increases plasma cortisol in proportion to INTENSITY of the stressful stimuli
-It can OVERRIDE the stabilizing NEGATIVE FEEDBACK control
(you can keep getting signal of stress, keep stimulating hypo pituitary adrenal axis, and keep increasing cortisol).
Explain what occurs in the transport of cortisol. How is *cortisol transported? Where is the predominant site of steroid inactivation? What kind of short life does cortisol have?
Transport of Cortisol:
-Cortisol is predominantly Bound to Proteins in the blood
a. CORTICOSTERIOD-BINDING GLOBULIN (CBG, Transcortin)- 75%
b. Albumin 15-20%
c Unbound 5%
-Liver is the predominant site of Steroid Inactivation.
-It inactivates and conjugates with glucuronide or sulfate to increase solubility and facilitate excretion by kidney (pee out salt)
-Half-life : 70 min (short half life for cortisol)
*Describe the mechanism of action for Cortisol protein synthesis.
Mechanism of action:
- Adrenal steroids diffuse into target cell and interact with intracellular steroids
- Receptor is bound to other proteins, including heat shock proteins (HSP-90)
- Hormone binds to receptor- HSP complex, HSP released
- Activated receptor (steroid-receptor dimer) now has a high affinity for steroid-response element of DNA, binds.
- once bound to element of DNA, hormone-receptor complex acts as a transcription factor to regulate gene expression (mRNA)
What are the two therapeutically important consequences for cortisol protein synthesis?
Two therapeutically important consequens (protein synthesis)
- LAG PERIOD (30 mins- several hours) to produce their effects
- Time is required to synthesize new protein
- *GCC’s (glucocorticoids) will not immediately relieve acute bronchial asthma
- but combo of inhaled GCCs and Beta agonist (dilators) will help prevent and control asthma
- LAG PERIOD (30 mins- several hours) to produce their effects
- Effects can LAST for HOURS To DAYS due to SLOW turnover of enzymes and proteins.
*What are the main actions of cortisol?
4 main functions of Cortisol:
- stimulate gluconeogenesis in response to LOW blood glucose
- Increase protein and lipid breakdown (provides Gluconeogenesis substrates)
- Anti-inflammatory effects
- Suppress immune response.
