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66 Cards in this Set
- Front
- Back
What are the 2 compartments of the Adrenal Cortex and what do they secrete?
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1. Outer Zona Glomerulosa ➡ mineralcorticoid Aldosterone
2. Inner Zona Fasciculata ➡ Cortisol 3. Reticularis ➡ Adrenal Androgens |
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What regulates Aldosterone secretion from the Zona Granulosa?
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1. extracellular K+ channels that sense Potassium levels
-Hyperkalemia = secretion 2. Angiotensin receptors |
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What regulates the secretion of Glucocorticoids?
What are the 2 enzymes that catalyze Glucocorticoid production? |
ACTH
17a-hydroxylase (P450c17) 11b-hydroxylase (P450c11) |
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What is the naturally-occuring Glucocorticoid?
What is it derived from? |
Cortisol
Cholesterol |
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What 2 things are the synthesis and secretion of Cortisol tightly regulated by?
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CNS which is very sensitive to negative feedback by:
1. circulating Cortisol 2. Exogenous (synthetic) Glucocorticoids |
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__1__ mg of Cortisol is secreted daily following a Circadian rhythm regulated by __2__
3. What is the half-life of Cortisol? |
1. 10-20
2. ACTH 3. 60-90 min |
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What is 90% of circulating Cortisol bound to?
What about the other 5-10%? |
Corticosteroid binding globulin (CBG) = synthesized by Liver
Free or loosely bound to Albumin |
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How is Cortisol inactivated?
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Mostly in the Liver
1. ~ 20% is converted to Cortisone 2. only 1% is excreted in urine |
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Describe the Glucocorticoid receptors
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Primarily Cytoplasmic, in the form of Oligomeric complexes with 2 molecules of Heat Shock Proteins (Hsp90)
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List the 2 types of Glucocorticoid "orpha receptors"
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Type 1 = mineralcorticoid receptor; expressed mainly in organs of excretion such as kidney, colon, salivary glands, sweat glands
Type 2 = Glucocorticoid receptor; broader tissue distribution |
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Describe the Steroid-Receptor Interaction for Cortisol
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1. free steroid enter cell cytoplasm to release receptor from Hsp90
2. Steroid-receptor complex enters nucleus 3. S-R binds to the Glucocorticoid Response Element (GRE) 4. Regulates tsc by RNA polymerase and other factors 5. mRNA edited and exported to cytoplasm to form protein |
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What % of expressed genes do Glucocorticoids regulate in any given cell?
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10-20%
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What are Glucocorticoid effects mainly due to?
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Proteins synthesized from mRNA transcribed by their target genes
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What are the 3 main effects Glucocorticoids produce?
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1. Anti-growth
2. Anti-inflammatory 3. Immunosuppressive effects |
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Most of the effects of Corticosteroids (Cortisol) are __1__, while others are __2__
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1. direct
2. "permissive" = effects that required glucocorticoid presence such that the fxn becomes deficient when glucocorticoid is absent |
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Glucocorticoids induce the synthesis of __1__, an inhibitor of __2__
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1. Lipocortin
2. Phospholipase A2 **inhibits Prostaglandin and Leukotriene synthesis = Anti-inflammatory |
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Glucocorticoids inhibit the production of __1__, which inhibits the proliferation of __2__
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1. IL-2
2. T lymphocytes **Anti-inflammatory |
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Glucocorticoids inhibit the release of these 2 things from Mast cells and Platelets
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1. Histamine = decreases capillary permeability (usually causes permeability)
2. Serotonin = less platelet aggregation (usually causes aggregation) |
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How do Corticosteroids reduce the # of Lymphocytes, Monocytes, Eosinophils, and Basophils?
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causes them to move from the Vascular bed to Lymphoid tissues
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List the Metabolic effects Glucocorticoids (Corticosteroids) possess
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1. Stimulate Gluconeogenesis and Glycogen synthesis
2. release Amino Acids during muscle catabolism = provide AA's to liver for Gluconeogenesis 3. Stimulate hormone-sensitive Lipase & Lipolysis = provides more glycerol to liver for gluconeogenesis 4. Elevate serum Glucose to stimulate Insulin release BUT inhibit glucose uptake by muscle cells = allows more delivery to brain |
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What is the ultimate purpose of the Metabolic effects of Cortisol?
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Supply adequate glucose to the brain in the fasting state
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Where do the Catabolic & Anabolic effects of Glucocorticoids occur?
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1. Lymphoid tissue
2. Connective tissue 3. Muscle 4. Fat 5. Skin |
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What effects do supraphysiologic amounts of Corticosteroids have on muscle, skin, and bone?
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Reduce muscle mass causing weakness
Skin thinning Osteoporosis (in Cushing's syndrome) |
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Reduced growth in children on Corticosteroids can be partly prevented with what?
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high doses of Growth Hormone
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What effects do Glucocorticoids have on the CNS?
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1. marked slowing of EEG alpha rhythm
2. behavioral disturbances initially as insomnia & euphoria followed by depression 3. large doses may increase Intracranial pressure 4. suppressed Pituitary release of ACTH, GH, TSH, LH |
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Describe how Cortisol maintains vascular responsiveness to catecholamines
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cortisol up-regulates Alpha1-receptors on arterioles, increasing vasoconstrictor effect of Norepinephrine
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How could Glucocorticoids contribute to Peptic Ulcers?
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by suppressing local immune response to H. pylori
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List 3 miscellaneous effects of Corticosteroids
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1. promote fat redistribution to increase visceral, facial, nuchal and supraclavicular fat
2. antagonize Vitamin D effect on intestinal Calcium absorption 3. increase numbers of platelets and RBC's |
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What effect does Cortisol deficiency have on renal function?
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Impairs renal function and augments (increase) Vasopressin (ADH) secretion resulting in an inability to excrete a water load normally
**Vasopressin (ADH) causes increased water reabsorption = decreased urination volume |
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When would Glucocorticoids be given to fetuses?
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When they are premature = stimulate structural and functional development of fetal lungs including the production of Surfactant
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List the names of commonly used Glucocorticoids (6)
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1. Hydrocortisone
2. Prednisone 3. Triamcinolone 4. Betamethasone 5. Dexamethasone 6. Beclomethasone |
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How are the synthetic Corticosteroids traditionally grouped? What are their actions?
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Glucocorticoids = affect glucose metabolism & inflammation
Mineralcorticoids = affect Na+ or Salt retention **the 2 groups of effects are usually not closely related & reflect distinct actions at 2 distinct receptors |
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2 steroids classified as Glucocorticoids but also have some Mineralcorticoid activity
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Cortisol
Prednisone |
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Steroid classified as a Mineralcorticoid but also affects Glucose metabolism (Glucocorticoid)
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Fludro-cortisone
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2 Steroids that have strong anti-inflammatory action but no salt-retaining activity
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Beta-methasone
Dexa-methasone **are also long-lasting |
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Steroid that has Salt-retaining activity but no anti-inflammatory activity
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Des-oxy-cortico-sterone
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What steroids should be used whenever Electrolyte Abnormalities are present?
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Corticosteroids without Salt-retaining activity
-Methylprednisolone -Triamcinolone -Betamethasone -Dexamethasone |
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What are the 2 Corticosteroids that have potent Salt-retention activity?
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Des-oxy-cortico-sterone
Fludro-cortisone |
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2 Corticosteroids that have high Anti-inflammatory activity but no Salt-retention activity
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Beta-methasone
Dexa-methasone **both are long-acting |
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What is the treatment regimen for Adrenocortical Insufficiency (Addison's disease = adrenal atrophy)
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Life-long combined glucocorticoid and mineralcorticoid; use HYDROCORTISONE + Mineralcorticoid (Fludro-cortisone)
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What should you not use to treat Adrenocortical Insufficiency (Addison's disease)?
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Glucocorticoids that have no salt-retaining activity
-Methylprednisolone -Triamcinolone -Betamethasone -Dexamethasone |
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1. What is the cause of Bilateral Adrenal Hyperplasia (Cushing's disease)?
2. List the main characteristics 3. What is the treatment? |
1. ACTH-secreting pituitary adenoma
2. moon facies, trunk obesity, muscle wasting, purple striae, skin bruising, osteoporosis 3. large dose Hydrocortisone following surgical removal of tumor |
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Condition referred to as "iatrogenic complication of long-term corticosteroid therapy"
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Cushing's syndrome
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What is used to treat Aldosteronism (aldosterone excess resulting from Adrenal Adenoma)
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Spirono-lactone
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Describe the "Dexamethasone Suppression Test"
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used to diagnose Cushing's disease
-high cortisol levels are reduced to 50% by Dexamethasone |
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Are glucocorticoids curative or not curative in Nonadrenal disorders?
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Not curative, and whenever possible should be used only to supplement specific treatment for the disease
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What are the most commonly used Glucocorticoids used to treat NONADRENAL disorders? (6)
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1. Beta-methasone
2. Dexa-methasone 3. Hydrocortisone 4. Prednisolone 5. Methyl-prednisolone 6. Triam-cinolone |
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What 3 principles should be kept in mind when using Glucocorticoids to treat CHRONIC Nonadrenal disorders?
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1. procede carefully with LOW DOSES
2. Intermittent administration (i.e. alternate days) 3. DO NOT DISCONTINUE ABRUPTLY |
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What can minimize systemic side-effects when giving Glucocorticoids?
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Local administration
-hydrocortisone by enema for Ulcerative Colitis -inhaled steroids for asthma |
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Toxicity of Synthetic Glucocorticoids:
When used for less than __1__ serious side-effects are infrequent, but these 3 things may occur: __2__ |
1. 2 weeks
2. Insomnia, Behavioral changes, Acute peptic ulcers |
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List the major side effects of Synthetic Glucocorticoids that may occur if given for long periods of time
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1. Metabolic side-effects resulting from the hormonal actions = Iatrogenic Cushing's Syndrome
-moon facies, truncal obesity, punctate acne, muscle wasting, skin thinning, osteoporosis, diabetes 2. Peptic ulcer, myopathy, acute psychosis, depression, glaucoma, HTN, Fluid retention & edema 3. Adrenal suppression resulting in Anorexia, nausea or vomiting, weight loss, lethargy, headache |
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In what patients should caution be used when giving Synthetic Glucocorticoids? (8)
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1. Peptic ulcer
2. Heart disease 3. HTN (up-regulate Alpha-1 receptors on arterioles) 4. Psychoses 5. Infections 6. Diabetes 7. Osteoporosis 8. Glaucoma |
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The most important mineralcorticoid in man that is synthesized in the Zona Glomerulosa
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Aldosterone
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Where does Aldosterone bind?
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receptors in:
1. Distal Convoluted tubule 2. Proximal Collecting tubules Promotes Na+ reabsorption |
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What is the precursor of Aldosterone that is also normally synthesized and secreted?
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Deoxy-cortico-sterone
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Most commonly prescribed Mineralcorticoid; has potent Glucocorticoid and Mineralcorticoid activity
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Fludro-cortico-sterone
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Mineralcorticoid that is used to treat Adrenocortical insufficiency associated with Mineralcorticoid deficiency
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Fludro-cortico-sterone
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SELECTIVE INHIBITOR of STEROID SYNTHESIS commonly used for testing adrenal function
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Mety-rapone
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Nonselective inhibitor of Adrenal & Gonadal steroid synthesis used for treatment of Cushing's Disease
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Ketoconazole
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Glucocorticoid antagonist with strong Anti-progestin activity and has been used as an Abortifacient?
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Mife-pristone
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Aldosterone antagonist widely used to prevent Hypokalemia in treatment of HTN and Congestive Heart Failure
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Spironolactone
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