Term
| The adrenal consists of two distinct secretory glands within a single capsule. How much percent of the total gland does each constitute, what embryological origin does it come from, and what does it secrete? |
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Definition
- Cortex is yellow due to high fat content, constitues 80% of total gland, is derived from mesoderm, and manufactures steroid hormones.
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- The medulla is red due to rich blood supply, constitues 20% of total gland,is derived from neuroectoderm, and synthesizes catecholamines
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Term
| What are the 3 different secretory cells of the adrenal? |
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Definition
- zona glomerulosa
- zona fasciculata
- zona reticularis
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Term
| The zona glomerulosa cells constitute 5% of the adrenal and they exclusively synthesize.. |
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Definition
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Term
The zona fasciculata cells constitute 80% of the adrenal and they exclusively synthesize..
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Definition
| Cortisol, the most potent glucocorticoid. |
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Term
| What 2 hormones does the zona reticularis synthesize? |
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Definition
| Androstenedione and dehydroepiandrosterone (DHEA). there extra-adrenal conversion of those two to testosterone and estrogen and thus considered sex hormone precursors. |
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Term
| what supplies the adrenal with fresh blood and what drains it? |
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Definition
| Each adrenal is supplied by aorta, renal artery, and inferior phrenic; but each is drained by just a single central vein. |
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Term
True or False In the adrenal, blood flow directionally is from outer cortex to the medulla; basal flow is high and can increase substantially during stress, a response mediated by pituitary secretion of adrenocorticotrophic hormone (ACTH) |
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Definition
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Term
The increase in intravascular pressure within the adrenal during stress predisposes the it to spontaneous massive bilateral hemorrhage, especially in patients with hemorrhagic diatheses such as those on anticoagulants or anti-platelet agents. What are 2 physiologic reasons that effect this predisposition?
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Definition
- The fact that the central vein draining each side is under constant concentrated catecholamine exposure causes it to constrict.
- Exposure of the adrenals to high basal arterial pressure.
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Term
True or False Spontaneous bilateral adrenal hemorrhage is an important and sometimes unrecognized cause of acute adrenal insufficiency, a life-threatening condition in which profound hypotension is usually the cardinal and sometimes the only clinical finding. |
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Definition
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Term
| In the fetus when is the adrenals histologically recognizable? |
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Definition
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Term
| During fetal life what are the names of the layers constituting the adrenals? |
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Definition
10% "definitive" cortex 90% "fetal" zone |
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Term
| after birth this layer of the adrenal regresses. what is it? and when does it regress? |
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Definition
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Term
- zona glomerulosa and fasciculata become fully developed when?
- zona fasciculata is formed when and fully developed when?
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Definition
- between 1-3 years.
- formed by 1year & fully developed by puberty
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Term
| what does the fetal 'definitive' zone produce, and how does that change with the growing fetus? |
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Definition
| 25% of fetal plasma cortisol, the rest is derived from the mother via transplacental transport. However, by term, about 75% of fetal plasma cortisol is derived from the developing outer zone of adrenal and only 25% from the mother. |
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Term
| what is the predominant hormone of the fetal zone of the developing adrenal gland, and what is its role? |
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Definition
| DHEA. it serves as a precursor for synthesis of placental & circulating estrogen. |
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Term
True or False Fetal adrenal androgen production is a determinate of the sexual phenotype of the newborn, that is of differentiation of the external genitalia. |
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Definition
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Term
| When do DHEA and androstenedione levels from a developing zona reticularis begin to increase? |
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Definition
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Term
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Definition
| The increase in adrenal androgen production which mediates physiologic changes consisting of a brief pre-pubertal growth spurt and the appearance of pubic and axillary hair.. occurs around 7-9 years of age. |
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Term
| Adrenal DHEA production and plasma levels of DHEA continue to change as a function of age, reaching a peak at what age? |
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Definition
| 3rd decade, and declines thereafter. |
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Term
| pituitary ACTH, adrenal cortisol or aldosterone secretion reach adult levels at a certain age and remain constant throughout life in healthy adults. what is that age bracket? |
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Definition
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Term
| All human steroid hormones are derived from what? |
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Definition
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Term
| The initial and rate limiting biosynthetic step in the conversion of cholesterol to steroids is what? |
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Definition
| cleavage of the cholesterol side chain to generate a C21 four ringed structure (pregnenolone). |
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Term
| The adrenal cortex synthesizes all classes of steroids in variable amounts including small quantities of estrogen and testosterone. Indeed, most of the steroid biosynthesis pathway is shared by the gonads and adrenal cortex. However, only the adrenal synthesizes cortisol and aldosterone, why? |
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Definition
| this require expression of 11Beta hydroxylase activity and aldosterone synthase activity, respectively. The latter two enzymes are not expressed in gonadal cells. |
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Term
True or False the enzyme which catalyzes cholesterol side chain cleavage and the gene which encodes it are both identified as CYP11A1. Some genes encode more than one enzymatic activity, for CYP11B2 (aldosterone synthase). |
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Definition
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Term
True or False Steroid hormones are synthesized as needed in response to physiologic regulators and are not stored within the adrenal. |
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Definition
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Term
| The concentration of this hormone in the plasma is highly dependent upon salt intake and hemodynamics. |
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Definition
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Term
True or False Of the major adrenal steroids, only cortisol circulates predominately bound to a high affinity transport protein. Approximately 90% of circulating cortisol is bound to cortisol binding globulin (CBG or transcortin), an alpha-globulin synthesized in liver. |
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Definition
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Term
True or False Cortisol bound to cortisol binding globulin (CBG or transcortin) is biologically INACTIVE cortisol. |
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Definition
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Term
| Estrogen increases CBG and total cortisol levels. Nephrotic syndrome lowers total plasma cortisol due to loss of large quantities of CBG through urine. In both conditions, why do patients not have manifestations of cortisol deficiency? |
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Definition
| In both conditions, what changes really is CBG, while unbound cortisol remains unchanged. Unbound, free, cortisol is the biologically active form and is thus unaffected. |
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Term
| How are steroid hormones inactivated? How are they excreted? |
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Definition
| hepatically inactivated & excreted in the urine. |
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Term
| At its highest concentration in the plasma, this hormone's concentration in the plasma at any one moment remains the lowest amongst the other adrenal hormones. It also has the lowest production rate (mg/day) as compared to the rest of the hormones. |
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Definition
| Aldosterone with 0.01 - 0.02 ug/dl. |
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Term
| What enzyme catalyzes the extra-adrenal conversion of adrenal androgens to estrogen? Where is it located. |
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Definition
| Enzyme P450 aromatase; it is located in fat cells. |
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Term
| Why do circulating estrogen levels generally increase as a function of body fat content? |
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Definition
| Fat cells express the P450 aromatase enzyme which converts adrenal androgens to estrogen. As fat cells increase, so does expression of the enzyme. |
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Term
| What is the primarly responsible for the regulation of the synthesis and secretion of aldosterone by glomerulosa cells? |
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Definition
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Term
True or False Normal basal secretion of ACTH and cortisol occurs in a pulsatile pattern and demonstrates a circadian rhythm which follows the sleep-wake cycle. |
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Definition
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Term
True or False First, “normal” values for plasma cortisol are dependent on the time of day. Thus, typical 8:00AM plasma cortisol values are in the 15-20 ug/dl range, whereas early evening values are typically less than 10 ug/dl. Second, about 65% of total daily adrenal secretion of cortisol (~15 mg/day) occurs between 6:00AM and 2:00PM. |
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Definition
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Term
| when prescribing basal cortisol replacement therapy for patients with adrenal insufficiency, how is the dose adjusted? |
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Definition
| Adjusted to reflect that in normal subjects the majority of cortisol release occurs in the morning with levels decreasing through the afternoon and evening. So, two-thirds of the total daily dose is given in the morning and one-third in the evening. |
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Term
True or False A variety of acute and chronic stressful stimuli, including vigorous exercise, cold exposure, fever, hypotension, trauma and hypoglycemia, acting through incompletely defined central nervous system pathways stimulate hypothalamic secretion of CRH, and consequently secretion of ACTH and cortisol. |
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Definition
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Term
| What are 3 acute effects of ACTH on the adrenal gland? |
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Definition
Increases: - Blood flow
- Cholesterol -> pregnenlone
- Cortisol (2-5min)
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Term
| What are 3 chronic (via cAMP response elements (CRE)) effects of ACTH on the adrenal gland? |
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Definition
Increases: - adrenal mass
- synthesis of steroidogenic enzymes
- LDL receptors
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Term
| Low plasma cortisol and high plasma ACTH signals what kind of condition? |
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Definition
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Term
| How can you discern a secondary adrenal failure by just looking at the levels of cortisol and ACTH? |
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Definition
| both levels of ACTH and cortisol should be low. |
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Term
| The genomic mechanisms for expression of the actions of all steroid hormones on cells are similar. What kinds of plasma membrane receptors do cells have to effect such signals? |
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Definition
Cells possess no such membrane receptors for the genomic effects of steroid hormones; in fact those pathways rely on receptors internal to the cells. As with other steroids,a steroid hormone (G) is thought to enter cells by passive diffusion across the plasma membrane and then bind to a specific cytoplasmic receptor protein (R). The GR complex then mediates the cellular actions via the genomic pathways. |
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Term
| Explain the 2 genomic pathways by which glucocorticoids mediate their action on cells. |
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Definition
They bind w/cytoplasmic receptor and enter the nucleus to bind to regulatory squences forming a glucocorticoid response element (GRE) and function as transcription factors.
The glucocorticoid steroid/receptor complex binds to cytoplasmic protein, thereby inhibiting their action - one such example is NF-kappaB.
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Term
True or False The actions of glucocorticoids mediated by their genomic effects take hours to days. |
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Definition
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Term
True or False The non-genomic actions of glucocorticoids takes minutes rather hours to days. |
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Definition
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Term
True or False The potency of steroid hormones as glucocorticoids correlates with their affinity for the Type 2, glucocorticoid, receptor. |
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Definition
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Term
True or False The potency of steroid hormones as mineralocorticoids DOESN't correlate with their affinity for the Type 1, mineralocorticoid receptor. |
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Definition
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Term
True or False In contrast with Type 1 mineralocorticoid receptors whose distribution of cellular expression is more limited, glucocorticoid receptors are ubiquitous in their cellular distribution. The biologic actions of glucocorticoids are correspondingly very diverse. |
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Definition
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Term
| What are the 3 effects of glucocorticoids on carbohydrate metabolism? |
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Definition
- Maintain hepatic glycogen stores.
- Maintain hepatic gluconeogenesis;and the actions of epinephrine and glucagon on this process.
- Reduce peripheral glucose utilization (muscle, fat).
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Term
| What is the mechanism by which glucocorticoids mediate maintaining of hepatic glycogen stores? |
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Definition
| Activate glycogen synthase; inactivate phosphorylase. |
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Term
| What is the mechanism by which glucocorticoids mediate maintaining hepatic gluconeogenesis? |
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Definition
| Mobilize gluconeogenic precursors (amino acids, glycerol). Activate gluconeogenic enzymes (glucose-6-phosphatase, PEPCK) |
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Term
| What is the mechanism by which glucocorticoids mediate reducing peripheral glucose utilization (muscle, fat)? |
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Definition
| Reduced insulin action in part via decreasing GLUT 4 mediated glucose transport. |
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Term
| What are the 2 effects of glucocorticoids on lipid metabolism? |
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Definition
- Acute – activation of lipolysis at some sites with release of fatty acids, glycerol.
- Chronic – Central fat accumulation with chronic excess of cortisol.
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Term
| What is the mechanism by which glucocorticoids induce lipid metabolism acute effect (activation of lipolysis at some sites with release offatty acids, glycerol)? |
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Definition
| Increased sensitivity to lipolytic actions of catecholamines and hGH;reduced fat cell glucose uptake. |
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Term
| What is the mechanism by which glucocorticoids mediate lipid metabolism chronic effect (Central fataccumulation with chronic excess of cortisol)? |
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Definition
| Uncertain, associated with increased insulin levels which may interactwith cortisol to increase lipogenesis at central sites. |
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Term
| What is the effect of glucocorticoids on protein metabolism? |
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Definition
| Protein loss from muscle, connective tissue in skin, bone, other sites with release of amino acids. |
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Term
| What is the mechanism by which glucocorticoids mediate protein metabolism effects? |
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Definition
| Increase proteolysis; suppress synthesis; some extracellular matrix proteins;fibroblast growth |
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Term
| What is the effect of glucocorticoids on bone? |
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Definition
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Term
| What is the mechanism by which glucocorticoids mediate their effect on bone (osteopenia)? |
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Definition
| Inhibit osteoblast activity and thus suppress bone formation; suppress release of cytokines involved in osteoblast regulation. |
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Term
| What is the effect of glucocorticoids on the GI system? |
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Definition
| Suppress GI absorption of calcuim. |
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Term
| What is the mechanism by which glucocorticoids mediate their effects on the GI (decrease Ca++ absorption)? |
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Definition
| Reduced GI sensitivity to 1,25(OH)2D. |
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Term
| What are the effects of glucocorticoids on the cardiovascular system? |
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Definition
| Maintain normal cardiac output and vasomotor tone. |
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Term
| What is the mechanism by which glucocorticoids mediate their effects on the cardiovascular system? |
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Definition
Not fully understood; increases sensitivity of the vessels to catecholamines and other pressors; increases receptor numbers for vasopressors; increases smooth muscle cell Ca2+ uptake; suppress vasodilator (PGs and NO) synthesis |
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Term
| What are the 2 renal effects of glucocorticoids? |
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Definition
- Maintain of normal free water clearance.
- Sodium retention, potassium wasting and hypertension.
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Term
| What is the mechanism by which glucocorticoids mediate maintenance of normal free water clearance? |
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Definition
| Tonic suppression of ADH release and maintenance of normal cardiac output. |
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Term
| What is the mechanism by which glucocorticoids mediate sodium retention, potassium wasting and hypertension? |
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Definition
| Mineralocorticoid action of very high levels of cortisol in kidney via the Type 1 receptor. |
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Term
| What effects CNS do glucocorticoids have? |
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Definition
| Modulate mood, sleep-patterns, cognition, behavior. Their mechanism of actinon is uncertain. |
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Term
| What hematological effects do glucocorticoids have? |
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Definition
| Maintain normal erythropoiesis(anemia with cortisol deficiency and polycythemia with excess). Their mechanism of action their is uncertain. |
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Term
| What anti-inflammatory effects do glucocorticoids have? |
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Definition
Suppress multiple mediators of inflammation; suppress T-lymphocyte function; suppress B-lymphocyte eosinophil and macrophage
function and numbers. |
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Term
| What is the mechanism by which glucocorticoids mediate their anti-inflammatory effects? |
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Definition
| Inhibit NF-kappaB mediated gene transcription. Reduce production of inflammatory cytokines, (ILs, TNF, PGs, leukotrienes). |
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