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39 Cards in this Set
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Describe how norepinephrine in the cytoplasm is converted to epinephrine in the chromaffin granule
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Norepinephrine is synthesized in the secretion granule, and then moves into the cytoplasm where almost all is converted to epinephrine by the cytoplasmic enzyme PNMT. Epinephrine is actively transported back into the granule for secretion
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How does epinephrine influence metabolic pathways in the liver?
In adipose tissue? |
Epinephrine acts as a counter-regulatory hormone at the liver, it stimulates glycogenolysis, gluconeogenesis, and ketogenesis.
At the adipocyte, epinephrine has a strong lipolytic action through the activation of hormone sensitive lipase (HSL) |
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Explain how catecholamines can cause vasoconstriction in some blood vessels, while causing vasodilation in others
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Catecholamines act through binding to adrenergic receptors. The primary action on a given organ will be determined by the relative density of the different adrenergic isotypes. The beta2 adrenergic receptor is coupled to the Gs/cAMP/PKA pathway, which promotes vascular smooth muscle relaxation and thus, vasodilation.
Other vessles have alpha-1 receptors which would trigger constriction. |
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Why may the adrenal cortex atrophy when synthetic glucocorticoids are administered?
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Exogenous glucocorticoids inhibit ACTH, which normally is tropic to the adrenal cortex.
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Why may masculinization of women (adrenogenital syndrome) occur in patients with Cushing's disease?
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Excessice ACTH will drive adrenal androgen synthesis in the zona reticularis. The high levels of weak androgens lead to higher levels of testosterone and DHT bring produced peripherally in such cells as hair follicle cells.
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Explain the interaction of ENaC and SGK-1 in the actions of aldosterone
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Aldosterone increases the synthesis of ENaC (alpha su). Aldosterone also increases Sgk-1 gene expression. Sgk-1 prevents the ability of a protein, called Nedd 4-2, from trageting ENaC for degradation. Thus aldosterone promotes Na+ reabsorption by increasing the synthesis and stability of ENaC in the apical membrane of the distal tubule.
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Explain the differences between the cause of orthostatic hypotension in patients with orthostatic hypotension associated with pheochromocytoma and orthostatic hypotension associated with Addison's disease
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Orthostatic hypotension is due to loss of sympathetic tone to adjust for th epull of gravity on the blood. A pheochromocytoma produces chronic high levels of catecholamines , which down regulate all adrenergic receptors.
In Addisons disease, very low levels of aldosterone deplete the intravascular volume, reducing blood pressure. Low cortisol will decrease angiotensinogen production by the liver, and decreases adrenergic receptor expression (especially alpha1) and signaling in blood vessels. Further, very low levels of cortisol decrease PNMT levels, and thus, adrenomedullary production of epinephrine |
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Why are the consequences of a secondary pituitary ACTH insufficiency generally less severe than those of a primary adrenal insufficiency?
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Primary adrenal insufficiency involves aldosterone and glucocorticoid production, whereas secondary insufficiency involves only glucocorticoid production.
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What substances are produced by the Adrenal Cortex?
The Adrenal Medulla? |
Adrenal Cortex produces Steroids
Adrenal Medulla produces Catecholamines |
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How does ACTH stimulate the synthesis of steroid hormones?
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ACTH stimulates steroid synthesis by two mechanisms:
1. Stimulates the formation of free cholesterol in lipid droplets 2. Stimulates formation of pregnenolone in mitochondria - the rate-limiting step |
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How are adrenal steroids transported in circulation?
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Corticosteroid hormones are bound to plasma proteins in the circulation: Either by corticosteroid-binding globulin called transcortin (major transport protein) or by albumin.
It's important to remember that only free forms (unbound) of steroids are biologically active. |
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Adrenal steroids are metaboized by the ___ and excreted by the ____.
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Liver, Kidneys
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How is secretion of adrenal steroids regulated?
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Secretion of adrenal steroids is regulated by hypothalamo-pituitary adrenal pathway.
CRH -->ACTH --> Adrenal steroids CRH is stimulated by Hypoglycemia, Inflammation (via proinflammatory cytokines), Hemorrhage, Neurogenic stress (fear, trauma, anesthesia, surgery) Cortisol can feedback to inhibit: CRH, and ACTH secretion (fast response, minutes) and synthesis (slow response, hours) |
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At what time of the day are blood concentrations of ACTH and cortisol the highest?
At what time are they lowest? |
Peak levels occur in early morning (5-8 am)
Low levels occur in late evening (8pm - 3am) |
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What are some factors that can override the diurnal (night-day) pattern of cortisol release?
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Stress, sever pain and prolong exercise increase cortisol release
Analgesia (opiates, endorphins) decreases cortisol release |
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How are the effects of cortisol mediated? Where are the receptors located?
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Effects of cortisol are mediated via transcriptional mechanisms. It modifies gene expression via a cytoplasmic-nuclear protein receptor.
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What are the three major effects of cortisol?
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Energy metabolism: Cortisol increases plasma glucose level
Anti-inflammation:Cortisol suppresses function of the immune system Anti-stress: Cortisol mediates adaptation to long-term stress |
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Describe cortisol effects on energy metabolism
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Cortisol is catabolic. It...
Stimulates gluconeogenesis Causes the breakdown of skeletal muscle proteins Enhances lipolysis Causes negative calcium balance (decreases intestinal absorption, increases renal excretion, causes loss of calcium from bone tissue) |
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Describe cortisol's effect on muscle metabolism
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The overall effect is to stimulate the conversion of protein to glucose and the storage of glucose as glycogen.
Net protein catabolic actions result in ↑ amino acid levels in plasma, which increases their availability for gluconeogenesis. Cortisol increases plasma glucose levels resulting from ↓ glucose utilization and uptake: Cortisol reduces tissue sensitivity to insulin |
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Describe cortisol's effect on fat metabolism
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Cortisol increases plasma fatty acids and glycerol levels by enhancing lipolysis
Via stimulation of lipolytic enzymes (hormone sensitive lipase) Also directly inhibits lipogenesis |
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Describe cortisol effects on liver metabolism
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In the liver:
Cortisol stimulates gluconeogenesis and glycogen synthesis /storage Cortisol increases hepatic plasma protein synthesis |
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What are the anti-inflammatory actions of cortisol?
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Stabilizes Lysosomes
↓ Proteases & Histamine (reduces pain and function loss) ↓ Capillary Permeability ↓ Edema & Exudation (reduces swelling, pain and function loss) ↓ Blood Flow ↑ Vasoconstriction ↓ Vasodilation ↓ WBC Infiltration (reduces redness, swelling, heat, and pain) ↓ Immune Response ↓ Cytokines ↓ B & T Lymphocytes (prevents autoimmunity) |
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Describe what happens in acute stress (ie. hip dislocation)
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Cortisol increases
↓insulin/glucagon ratio ↑ Epi and Norepi In the Liver: ↑glycogenolysis ↑ gluconeogenesis Skeletal muscle: ↑ increased proteolysis ↓protein synthesis increased glycogenlysis ↓GLUT4-mediated glucose uptake Adipose tissue: ↑ lipolysis; ↓ lipogenesis, ↓GLUT4-mediated glucose uptake |
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Describe what happens in chronically elevated levels of cortisol (ie. In Cushing's disease)
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Increased cortisol.
↑ insulin/glucagon ratio ↑ appetite ↓ Epi and Norepi Liver: ↑glycogen synthesis Skeletal muscle: ↑ proteolysis ↓GLUT4-mediated glucose uptake Adipose tissue: ↓ lipolysis ↑ triglyceride synthesis ↓GLUT4-mediated glucose uptake |
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What is the primary mineralocorticoid?
What stimulates its secretion? |
Aldosterone is the primary mineralocorticoid.
Secretion is stimulated by the renin-angiotensin system: - Angiotensin II (direct effect) - High plasma [K+] (direct effect) - ACTH (direct effect) - Hypotension (indirect effect via renin-angiotensin system) |
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What are the effects of aldosterone?
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Aldosterone is the major regulator of Na+, K+, and fluid balance:
(Primary effect) Increases Na+ reabsorption (in) and increases K+ excretion (out) by increasing expression and activity of the Na,K- ATPase in the renal tubule cells (1) Increases H+ excretion (out) by the kidney (2) Increases blood pressure by increasing plasma volume: Increases water retention. This effect is secondary to Na+ retention and expansion of the extracellular fluid volume |
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What are examples of synthetic glucocorticoids?
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Prednisone, Methylprednisone, Dexamethasone (listed in increasing potentcy)
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What are the negative side effects of administering glucocorticoids?
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Suppresses endogenous secretion of CRH, ACTH, and cortisol
High doses of cortisol for extended time (5-7 days) cause Cushing syndrome |
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What are causes of adrenal cortex?
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Hypersecretion of adrenal cortex
Abnormally and chronically high level of cortisol Caused by Adenomas of the anterior pituitary that secrete large amounts of ACTH (Cushing’s disease) Abnormal function of the hypothalamus that causes high levels of CRH Ectopic secretion of ACTH Adenomas of the adrenal cortex |
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What are typical findings in Cushing's syndrome?
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Increased blood glucose (2x normal)
Decreased tissue proteins Mobilization and redistribution of fat Excess steroids Excess mineralocortoids Physical findings: Fat pads, pendulous abdomen, striae, moon face, red cheeks, ecchymoses, thin skin, poor muscle development, poor wound healing. |
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What is an example of primary hypoaldosteronism?
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Adrenal destruction,
Addison's disease These patients clinically present with hyponatremia, hyperkalemia, mild acidemia, hypotension |
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What is an example of primary hyperaldosteronism?
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Adenoma,
Conn's Disease These pts clinically present with hypernatremia, hypokalemia, mild alkalosis, and hypertension |
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What is 21-hydroxylase deficiency
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An adrenogenital syndrome.
21- Hydroxylase deficiency is the most common enzymatic disorder that account for this syndrome Adrenal androgens are produced in great excess, causing virilization Production of cortisol is low ACTH secretion is increased because the low cortisol production Clinically: in females, ambiguous genitalia can lead to incorrect gender assignment at birth |
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How are catecholamines synthesized?
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1.Tyrosine
2. DOPA 3. DOPAMINE 4. Norepinephrine (NE) 5. Epinephrine (EPI) |
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How are catecholamines secreted?
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Secretion is initiated by acetylcholine (Ach) released from the preganglionic axons:
Ach → the membrane depolarization → an influx of Ca2+ → exocytosis of vesicles Secretion can be stimulated by exercise, hypoglycemia, hemorrhage, and emotional stress |
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At rest, does NE or EPI have the greater plasma concentration?
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NE, it is 2.8x greater than EPI
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nōtus
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known, well-known, customary
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-a, -um
nōta, nōtum |
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What are the actions of the following adrenergic receptors?
alpha1 alpha 2 beta 1 beta2 |
Alpha1: Calcium
Alpha 2: Decrease adenylyl cyclase, decrease cAMP Beta1: increase AC, increase cAMP. Opens L type calcium channels in the heart Beta 2 - increase AC, increase cAMP |
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What are the physiological effects of medullary hormones?
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Increased rate and force of contraction of the heart muscle
Constriction of blood vessels Dilation of bronchioles Stimulation of lipolysis Increased metabolic rate Breakdown glycogen Dilation of the pupils Inhibition of certain"non essential" processes |
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