Term
| The most postent mineralocorticoid product of the human adrenal cortex is _________. |
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Definition
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Term
The zona glomerulosa and the zona fasciculata, (the principle site of cortisol synthesis) share the enzymatic capacity to convert cholesterol sequentially to deoxycorticosterone (DOC), a relatively weak mineralocorticoid. However, only glomerulosa cells express this particular enzyme, which catalyzes the final three steps in the conversion of DOC to aldosterone, including 11-beta-hydroxylation of DOC. This enzyme is ________________.
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Definition
| aldosterone synthase, (CYP11β2). |
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Term
| The activity of aldosterone synthase is regulated predominantly by ___________, whereas that activity of 11β-OHase, (CYP11β1), the final step in cortisol synthesis in the zona fasciculata is regulated by ________. |
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Definition
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Term
| These three tissues contain so-called "Type I" cytosolic steroid receptors (R), also called the mineralocorticoid receptor (MR) which bind aldosterone (A) with high affinity. |
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Definition
- distal nephron (mainly the cortical collecting tubule)
- Colon
- Salivary glands
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Term
| What are effects of Aldosterone on basal vs. luminal cells of the distal nephron? |
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Definition
- Aldosterone suppresses the normal rate of endocytic removal of ENac Channels in the luminal side of the cortical collecting tuble.
- Aldosterone conceurrently increases the number & activity of Na+, Ka+/ATPase trnasporters on the basal side of the cell.
(The result is enhaned sodium trnasport across the epithelial cell into the interstitial fluid in exchange of potassium ions). |
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Term
| What is the net renal action of aldosterone? |
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Definition
| Enhanced renal tubular reabsorption of sodium in exchange for potassium and hydrogen ions. |
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Term
| Hyperaldosteronism can lead to what 2 things? |
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Definition
| hypokalemia & metabolic alkalosis via net loss of potassium and hydrogen ions. |
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Term
Although a glucocorticoid, cortisol has some mineralocorticoid activity at the type I receptor. However, the selective mineralocorticoid action of aldosterone versus cortisol is determined by the presence of the microsomal enzyme __________, which converts cortisol to __________, a steroid which has less than 1% of the affinity for the Type I receptor as cortisol.
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Definition
| cortisone; 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2). |
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Term
| What are 3 pathologic conditions in which the mineralocorticoid action of cortisol may be expressed and cortisol per se may give rise to a mineralocorticoid excess syndrome. |
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Definition
- Some patients with Cushing's syndrome who have sufficiently high circulating cortisol levels to exceed the capacity of cellular 11β-HSD2 for conversion to cortisone.
- Those with congenital deficiency of 11β-HSD2.
- Patients who ingest excess quantities of natural licorice which contains glycyrrhizic acid, an inhibitor of 11β-HSD2.
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Term
| What are 2 regulators of adrenal secretion of aldosterone? |
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Definition
- Renin-angiotensin system
- Serum potassium concentration.
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Term
| Describe sequence of events that ultimately lead to release of aldosterone, beginning w/change of state of renal perfusion. |
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Definition
- Reduction in renal perfusion, secondary to reduction in circulating blood volume/pressure.
- renal juxtaglomerular cells release renin
- Renin hydrolyzes angiotensinogen produced by the liver and angiontensin I (Ang I) is produced
- AngI is converted to AngII via Angiontensin converting enzyme (ACE) present in vascula endothelial cells, especially in the lung.
- AngII is the stimulus for aldosterone secretion by the adrenal.
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Term
| What are the differences between primary and secondary hyperaldosteronism? |
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Definition
Primary Hyperaldosteronism: is a structural or functional abnormality of the adrenal cortex that may result in non-physiologic oversecretion of aldosterone. It is characterized by high serum aldosterone with conversely low renin serum levels. Secondary Hyperaldosteronims: is characterized by high serum levels of both aldosterone and renin, both as a compensatory physiologic response to a decrease in effective circulating volume, bp, reduced renal perfusion, and/or an increase in serum potassium. |
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Term
| How does potassium affect aldosterone secretion? |
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Definition
| High concentrations of extracellular (serum) potassium act directly on the zona glomerulosa cells as an independent stimulus to aldosterone secretion. This action of extracellular potassium may be mediated by membrane depolarization with a resultant increase in intracellular calcium by this pathway. |
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Term
| What are 4 clinical features of primary hyperaldosteronism? |
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Definition
- Hypertension
- Hyperkalemia
- Metabolic alkalosis
- Absence of edema
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Term
| What are 3 consequences of severe hypokalemia? |
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Definition
- Glucose intolerance
- Nephrogenic Diabetis insipidus
- Weakness, paralysis.
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Term
| Why do patients with Primary Hyperaldosteronism not experience edema, despite the sodium retaining action of aldosterone? |
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Definition
The magnitude of the expansion of the extracellular fluid volume in these patients is limited by compensatory renal tubular responses known as "mineralocorticoid escape", which limit the magnitude of sodium retention. Increased secretion of natriuretic peptides of cardiac origin constitutes part of this compensatory response.
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Term
| What are the 2 major etiologies for primary hyperaldosteronism, accounting for 95% of cases? |
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Definition
- Aldosterone Producing Adenoma
- Idiopathic hyperaldosteronims
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Term
| How does Aldosterone Producing Adenoma presents as compared to Idiopathic Hyperaldosteronism? |
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Definition
APA: typically develops in one adrenal gland and thus represents a unilateral source of excess aldosterone. It represents a cause of hypertension which potentially can be cured by surgical resection of only the involved adrenal gland. IH: can be bilateral hyperplasia of the zona glomeruosa and thus both adrenal glands contributes to excess aldosterone secretion. This condition is treated medically. |
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Term
| When is screening for PHA indicated? |
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Definition
- Hypertension with spontaneous or easily provoked hypokalemia (major indication).
- Hypertension with onset below the age of 20 or above age 60 (ages at which new onset of essential hypertension is uncommon)
- Hypertension refractory to multiple antihypertensive agents
- An adrenal mass discovered incidentally on abdominal CT or MRI
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Term
| What does screening procedure for PHA involve? |
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Definition
The procedures sets out to prove non-renin mediated hypersecretion of aldosterone. It involves concurrent determination of plasma aldosterone concentration (PA) by immunoassay and plasma renin activity (PRA) by assay of enzymatic activity, with calculation of the ratio of PA/PRA. Findings characteristic of PHA are the combination of a high PA and a low PRA with a resultant high PA/PRA ratio, which is consistent with non-renin mediated hypersecretion of aldosterone.
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Term
| High ratio of PA/PRA usually has a poor positive predictive value in extablishing a conclusive diagnosis of PHA in hypertesnsive patients. What other test could establish the confirmation of non-physiologic adrenal aldosterone secretion? |
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Definition
| Aldosterone Suppression Test. |
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Term
| Aldosterone Suppression Test could be achieved by 3 ways: |
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Definition
- chronic volume expansion: achieved by chronic oral sodium loading with measurement of 24 hr urinary aldosterone excretion, which should decrease significantly in normal subjects.
- Acute volume expansion with intravenous saline with measurement of plasma aldosterone, which should decrease in normal subjects.
- Acute inhibition of angiotensin II synthesis using an angiotensin converting enzyme inhibitor, such as captopril.
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Term
| A normal aldosterone suppression test would show what? |
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Definition
| Decrease of aldosterone to any mode of testing (chronic volume loading, acute volume loading, or AngII antagonism). |
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Term
| After determination of PA/PRA ratio and administering an aldosterone suppression test, PHA is determined. What other procedures can be used in further distinguishing the etiology of the PRA. |
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Definition
| CT scan, MRI, or adrenal venous sampling. |
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Term
| What is the preferred treatment for APA? |
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Definition
| unilateral adrenalectomy. |
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Term
| What is the preferred treatment for IHA? |
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Definition
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Term
| How is IHA medically managed? |
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Definition
- Mineralocorticoid blockers: Spironolactone, eplerenone.
- Epithelial sodium channel blockers (ENac): amiloride, triamtrerne.
- Antihypertensives, since the above meds don't control hypertension.
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Term
| What are the clinical manifestations of chronic aldosterone deficiency/resistance? |
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Definition
- Hyperkalemia
- Hyperchloremic acidosis
- variable degrees of negative sodium balance
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Term
| How does hyperkalemia contribute to metabolic acidosis? |
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Definition
| Hyperkalemia suppresses renal ammonia production and secretion. |
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Term
| What is the most common acquired form of isolated aldosterone deficiency not attributable to a medication? |
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Definition
| hyporeninemic hypoaldosteroism. |
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Term
| Describe hyporeninemic hypoaldosteroism. |
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Definition
- Associated with diabetic nephropathy and chronic interstitial nephritis with only modest decrease in renal function
- Defective intrarenal conversion of prorenin to active renin
- Impaired renal renin release
- No increase in PRA or PA in response to salt deprivation
- Hyperkalemia in the absence of overt volume contraction in adults
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Term
| The major clinic concern and often the only finding in patients with inherited, acquired or drug-induced isolated aldosterone deficiency or resistance states is __________________. |
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Definition
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Term
| What is the treatment for isolated aldosterone deficiency or resistance states? |
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Definition
They key is to protect agains hyperkalemia. - Dietary potassium restriction.
- Use of potassium wasting diuretics such as furosemide,
- Administration of the potent synthetic mineralocorticoid fludrocortisone (may all be helpful in controlling hyperkalemia in chronic hereditary or acquired aldosterone deficiency or resistance states).
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Term
| What are some of the drugs that induce aldosterone deficiency or resistance states w/Hyperkalemia? |
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Definition
Inhibition of synthesis/secretion of A (↓PA; ↑PRA)
ACE inhibitors/Ang II receptor blockers
Cyclosporine
Suppression of renin release (↓PA; ↑PRA)
β-blockers
Cyclooxygenase inhibitors (NSAIDs)
Interference with renal actions of A (↑PA; ↑PRA)
- MR blockers
Spironolactone
Eplerenone
- ENaC blockers
Amiloride
Triamterene
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