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38 Cards in this Set
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- Back
- 3rd side (hint)
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(1) what does the adrenal medulla produce? (2) what does the zona fasciculata and reticularis of the inner adrenal cortex produce?
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catecholamines: epinephrine and noreepinephrine
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glucocorticoids
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(1) what does the zona reticularis of the inner adrenal cortex produce? (2) what does the zona glomerulosa of the outder adrenal cortex produce?
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sex steroid precursors like androstenedione
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mineralocorticoids
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(1) what controls the secretion of glucocorticoid?
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hypothalamic-pituitary adrenal axis (HPA)
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(1) what is the positive feedback of the HPA? (2) what is the negative feedback of the HPA?
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hypothalamus secretes CRH which stimulates pituitary ACTH secretion, anterior pituitary releases ACTH which stimulates cortisol release from adrenal cortex
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cortisol inhibits ACTH secretion by the pituitary and CRH secretion by the hypothalamus, ACTH inhibits CRH secretion by the hypothalamus
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(1) how is mineralocorticoid secretion controled? (2) how do corticosteroids cause their effects at the cellular level?
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decreased ECF volume > renin release > converts angiotensinogen to angiotensin I which ACE converts to angiotensin II causing release of aldosterone (also caused by increased K+ and ACTH which has weaker, permissive effect)
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steroid cross the cell membrane > blind to GC or MC receptor in cytoplasm > receptor-steroid complex moves to nucleus > receptor complex binds GC or MC response elements on DNA > receptor complex DNA binding causes RNA transcription > translation > proteins that carry out steroid response (GC receptors are ubiquitous - present in every cell type)
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(1) what is the overall effect of GC's? (2) how do they effect carb metabolism?
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overall catabolic hormones; accelerating protein catabolism, inhibiting DNA, RNA, protein synthesis
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maintain normal blood glucose (stim gluconeogenesis in liver, stim muscle catabolism > aa for glucose synthesis, inhibit muscle/adipose uptake of glucose, stim lipolysis) = ANTAGONIZE INSULIN, stim glycogen synthesis in liver providing reserves for future glucose needs
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(1) what is the other systemic affect of GC's? (2) what is the overall result?
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anti-inflammatory, immunosuppressive by reducing migrations of inflam cells to injury sites
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STRESS LEUKOGRAM
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(1) how do GC's affect blood vessels? (2) neutrophils?
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decrease vascular permeability making them less leaky and harder for white cells to leave to reach sites of infection by inhibiting synthesis of inflammatory mediators via lipocortin (prostaglandins and leukotrienes)
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cause a NEUTROPHILIA by inhibiting neutrophil movement out of the vascular space (diapedesis) and impain neutrophil's ability to phagocytose and destroy bacteria
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(1) how do GC's affect lymphocytes? (2) macrophages?
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cause a LYMPHOPENIA by causing lymphocytes to move from bood to spleen, lymph nodes, bone marrow. Impair cytokine production > inhibits lymphocyte proliferation and function
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prevent monocytes from leave the vasculature > MONOCYTOSIS. Inhibit the MP's ability to phagocytose extracelular material and therefore to act as an antigen presenting cell to B cells
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(1) how do CG's affect eosinophils?
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decrease eosinophil release from bone marrow > EOSINOPENIA
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(1) how do CG's affect the renal system? (2) CT?
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increase urination and thirst (PU/PD) by inhibiting ADH secretion and interfering with action ADH at renal tubular cells
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inhibit wound healing by inhibiting fibroblast proliferation
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(1) how do CG's affect calcium metabolism? (2) cardiovascular effects?
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decrease intestinal calcium absorption, increase bone calcium resportion > bone demineralization, increase urinary calcium excretion = NET EFFECT OF DECREASED BLOOD CA++ LEVELS
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increase vascular tone by increasing effect of vasopressors like epinephrine > hypertension in GC excess, hypotension in GC absense
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(1) what are the physiologic effects of mineralocorticoids?
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much simpler, but essential to life; aldosterone stimulates water and sodium resorption in distal renal tubule in exchange for potassium excretion, important for maintaining blood volume and normal electrolyte status, aldosterone works similarly in the colon to conserve body sodium and water
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(1) What is Cushing's syndrome? (2) what is it due to?
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hyperadrenocorticism
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EXCESSIVE PRODUCTION OF CORTISOL
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(1) what animal's can have Cushings? (2) what forms of Cushing's are there?
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dogs, horses, cats (rarely)
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pituitary dependent hyperadrenocorticism (PDH), Adrenal dependent hyperadrenocorticism (ADH), Iatrogenic
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(1) how does PDH Cushing's occur? (2) how does ADH Cushing's occur?
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pituitary tumor, usually a microadenoma, produces excessive ACTH which stimulates both adrenal glands to hypertrophy and produce excessive cortisol (85% of Cushings in dogs)
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Benign or malignant adrenal tumor excessively make cortisol INDEPENDENT of ACTH. Contralateral adrenal gland (the one without the tumor( atrophies because it is not stimulated by ACTH, since ACTH secretion is suppressed by the excessive cortisol made by tumor
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(1) how does iatrogenic Cushing's occur? (2) how does Cushing's present?
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prolonged GC administration can result in Cushing's syndrome
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muscle wasting and thin skin from GC catabolic effects, obese from fat breakdown and redistribution and inability of weak muscles to hold fat in place > pot belly, insulin antagonism > diabetes induction, glycogen production in liver > hepatomegaly, panting > weak respiratory muscles, pressure on diaphragm from fat and liver, PU/PD (can be life threatening), hypertension, immunosuppression
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(1) what screening tests are done for Cushing's?
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urine cortisol to creatinine ratio and ACTH stimulation test and Dexamethasone suppression test
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(1) what does a urine cortisol to creatinine ratio test for? (2) what does an ACTH stimulation test for?
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increased cortisol levels n urine relative to creatinine. Often elevated due to stress. If negative, can rule out Cushing's, if elevaeted nee to do more tests
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uses the HPA axis; measure baseline plasma cortisol, inject ACTH (natural or synthetic Cosyntropin) which asks adrenals to make more cortisol, measure post ACTH plasma cortisol level 30-120 min after injection (species dependent)
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(1) what does a dexamethasone suppression test for?
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uses negative feedback of HPA axis; measure baseline plasma cortisol, give 0.01 mg/kg of dexamethasone (potent GC), measure plasma cortisol 4 & 8hrs later. In a normal animals ACTTH release is suppressed by neg feedback on pituitary and hypothalamus, so a reduction in cortisol to <1.4 ug/dl after 8 hours. Animals with Cushing's do not show any reduction in cortisol from baseline
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(1) how do we treat Cushing's? (2) what meds can be used?
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surgery for adrenal tumors or medical treatment (best for PDH)
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Mitotane (lysodren), Trilostane, pergolide, Cyproheptadine
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(1) describe mitotane (2) describe trilostane?
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tried and true: O,P'-DDD similar to insecticide DDT, selectively destroys zona fasciculata and reticularis of adrenal cortex, loading dose for 7-10d, followed by maintenance dose (~2x/wk). Side effects of GI upset, CNS effects, idiosyncratic liver failure. Pros - inexpensive, lots of knowledge of this treatment
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inhibits steroid biosyntehsis by inhibiting the 3B hydroxysteroid dehydrogenase enzyme that converts pregnenlone to progesterone in cortisol, aldosterone, and sex steroid pathways. Pros = reversible, less toxic. Cons = adrenocortical necrosis reported, just recently FDA approved, not as much knowledge about it, more frequent dosing (SID to TID)
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(1) describe pergolide (2) describe Cyproheptadine
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dopamine agonist .dopamine Inhibits release of ACTH from anterior pituitary. Treatment used in horses; ineffective in small animals.
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eserotonin antagonist. Serotonin stimulates ACTH release from pituitary > cyproheptadine indirectly inhibits ACTH release. Another treatment used in horses, not successful in dogs.
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(1) what is addison's disease? (2) what is it caused by?
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hypoadrenocorticism
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DEFICIENCY OF BOTH CORTISOL AND ALDOSTERONE (ATYPICAL ADDISON'S IS JUST GC DEFICIENCY)
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(1) what species is Addison's seen in? (2) what are the causes
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dogs most commonly, rare in cats
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autoimmune destruction of the adrenal cortex
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(1) what are the signs of Addisons?
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lack of MCs: hyperkalemia, hyponatremia, dehydration, hypotension due to failure to conserve water and sodium and excrete potassium, hyperkalemia > cardia arrhythmias, PU/PD because hyponatremia leads to loss of renal medullary concentration gradient, PU/PD because hyponatremia leads to loss of renal medullary concentration gradient, dehydration leads to prerenal axotemia + PU/PD (looks like renal failure but isn't). GREAT PRETENDER. lack of GCs: lack of cortisol contributes to hypotension, disruption of carb metabolism > hypoglycemia, hypercalcemia, diarrhea and inappetance because GCs help maintain GI health, overall cannot respond to stress
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(1) what can occur with Addisonians? (2) how do you test for Addison's?
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state of hypotensive crisis in which they can die
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baseline cortisol level, ACTH stimulation test
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(1) describe baseline cortisol level (2) describe ACTH stimulation test
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if >2ug/dl, dog does not have addison's disease, if <2ug/dl, you don't know anything and have to do more testing
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test done like Cushing's, in Addisonian, ACTH will not be able to stimulate an increase in cortisol secretion
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(1) how do you treat addison's disease? (2) when treating a crisis?
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replace missing GCs (prednisone or prednisolone at 0.2 mg/kg/day, doubled in times of anticipated stress or dexamethasone in an emergency) and MCs (desoxycorticosterone pivalate: DOCP or Fludrocortisone acetate) at physiologic levels,
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fluid therapy with sodium chloride (0.9% NaCl)
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(1) what drug can be prescribed for Addisons?
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MC: desoxycorticosterone pivalate (DOCP) (percorten), of Fludricortisone acetate (Florinef)
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(1) describe Desoxycorticosterone pivalate (2) Fludricortisone acetate
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used in management of Addison's, given IM/SQ every 25-30 days (2.2 mg/kg), potential side effects (rare): hypokalemia, hypernatremia, hypertension
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synthetic MC used in Addison's management, orally-active, given daily (0.02 mg/kg), also possesses GC effects (DOCP does not) > may end up with signs of GC excess without enough MC effect, 50% dogs taking florinef as a MC replacement still need added GC replacement, cannot give in an addisonian crisis because oral only
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(1) what does aldosterone stimulate (2) what does fludrocortisone stimulte?
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mineralocorticoid (500) but glucocorticoid (~0)
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mineral ocorticoid (150) but glucocorticoid (10-20)
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(1) what does dexoxycorticosterone (SQ/IM only) stimulate? (2) what are the advantages of synthetic derivatives?
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mineralocorticoid (50) but glucocorticoid (0)
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created to increase duration of action, decrease MC actitivity (may be undersirabl increases sodium and water retention > bloating), and increase anti-inflammatory potency, combining steroid bases with insoluble esters can decrease their rate of absorption (IM) and increase their duration of action
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(1) describe prednisone
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most widely used GC in small animal practice, 4x cortisol's GC potency, less than half its MC potency, intermediate acting, actions last 12-36 hours, can be used for alternate day therapy, pro-drug of prednisolone (prednisone: ketone groups C11 > prednisolone: OH group C11 in liver), use prednisolone in patient's with liver disease
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(1) what do you use glucocorticoid preparations for?
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replacement therapy (Addison's disease), anti-inflammatory/anti-allergy therapy (pruritic dermatitis, asthma, arthritis), immunosuppressive therapy (conditions with a hyperactive immune system like immune-mediated polyarthritis, immune-mediated hemolytic anemia, systemic lupus erythematosus with gigh doses of long duration treatement), anti-neoplastic therapy (lymphoma, multiple myeloma, mast cell tumors), ophthalmi therapy (uveitis, chorioretinitis, etc), Skin therapy (inflammatory dermatoses (topical preparations and oral therapy), hypercalcemia management
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(1) what are the appropriate dose ranges for therapy? (2) what is an equivalent dose in dexamethasone?
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physiologic (Addison's) =0.2 mg/kg/day, anti-inflammatory =0.5-1.0 mg/kg/day, 2.2-4.4 mg/kg/day, 2.2-6.6 mg/kg/day (more like 2-4 mg/kg/day)
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(dose in prednisone) / (7)
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(1) why should we use caution when using Glucocorticoids? (2) what are the side effectsof corticosteroids?
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other GC effects cannot be separated from GC anti-inflammatory effects, side effects of GCs occur commonly, side effects are exaggerations of normal GC actions, gastrointestinal bleeding ulcers/perforation; pancreatitis, immune system infection/sepsis, especially of genitourinary tract, skin, and lungs
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cardiovascular: hypertension, hypercoagulability (form inappropriate clots), endcrine: hyperglycemia, poor diabetic control, induction of diabetes in cats, endocrine: iatrogenic Cushing's syndrome, followed by iatrogenic Addison's if exogenous GC withdrawn without tapering
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(1) rules of thumb for respecting steroids?
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treat underlying disease if possible, alternate day therapy allows HPA axis to recover on off days, withdraw steroids carefully (taper to allow HPA axis to recover), be aware of drug interaction (No NSAIDs with steroids and aspirin is a drug), use short acting steroid perparations wenever possible (Avoid using long-acting insoluble esters), remember ophthalmic and topical steroids are absorbed and do have side effects
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