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Case 18: Chemical Pathology (Endocrine Causes of Hypertension), NOTE: If…

- - - - Treatment of High Blood Pressure (Hypertension)
        Outline the Treatment of Hypertension
        Treatment of Hypertension is aimed at the mechanisms that increase Blood Pressure such as:
        
        ACE Inhibitors
        
        ACE Inhibitors are tablets that inhibit the ACE enzyme
        
        This decreases the production of Angiotensin II
        
        Inhibition of the Angiotensin II Receptor
        
        Spironolactone
        
        Spironolactone allows for the Inhibition of Aldosterone from binding to its Mineralocorticoid Receptor
        
        This prevents the function of the Na+/K+ ATPase Channel and Epithelial Sodium(Na+) Channel
        
        Decreases Hypertension
        
        Amiloride
        
        Amiloride allows for the Inhibition of the Epithelial Sodium (Na+) Channel in the Renal Distal Tubules
        
        Inhibition of the Epithelial Sodium (Na+) Channel in the Renal Distal Tubules prevents the reabsorption of Sodium and Water into the Distal Tubules
        
        Decreases Hypertension
        
        Mechanism of Action of Aldosterone in the Renal Distal Tubules
        Describe the Mechanism of Action of Aldosterone in the Renal Distal Tubules
        
        Aldosterone is a steroid hormone
        
        Aldosterone binds the Mineralocorticoid Receptor in the Nucleus inside the Renal Distal Tubular cells
        
        The binding of Aldosterone to the Mineralocorticoid Receptor causes an:
        
        Increase in the expression of the Na+/K+ ATPase Channel in the Basal Membrane
        
        Increase in the expression of the Epithelial Sodium Chanel (ENaC) in the Apical Membrane
        
        An Increase in the expression of the Epithelial Sodium Channel (ENaC) allows for an increased uptake of Sodium into the Renal Distal Tubular cells
        
        With an equal loss of Potassium and Hydrogen ions
        
        If the Aldosterone Action is excessive then there will be:
        
        Hypernatraemia
        
        Due to an increase reabsorption of Sodium into the Distal Tubules
        
        Hypokalaemia
        
        Due to an Increase in the Renal Excretion of Potassium
        
        Alkalosis
        
        Due to an Increase in the Renal Excretion of Hydrogen ions
        
        Hypertension
        
        Primary Hyperaldosteronism (Conn's Syndrome)
        Outline the presentation of Primary Hyperaldosteronism (Conn's Syndrome)
        
        Primary Hyperaldosteronism (Conn's Syndrome) usually presents with:
        
        Hypertension
        
        Increased Aldosterone
        
        Decreased Renin
        
        Mild Hypernatraemia
        
        Hypokalaemia
        
        Alkalosis
        
        Urine will have an increase in Potassium due to the Increased Renal Excretion of Potassium Ions
        
        More than 30 mmol/day of Potassium Ions are excreted in Primary Hyperaldosteronism (Conn's Syndrome)
- - - - Renal Artery Stenosis
        Outline the presentation of Renal Artery Stenosis
        
        Renal Artery Stenosis usually presents with:
        
        Hypertension
        
        Increased Aldosterone
        
        Increased Renin
        
        Hypokalaemia
        
        Alkalosis
        
        Hyponatraemia
        
        Hypokalaemia is due to the increase renal excretion of Potassium
        
        Alkalosis is due to the increased renal excretion of Hydrogen Ions
        
        Hyponatraemia is to the increased Water Retention as a result of increase Angiotensin II production
        
        Increased Water in the ECF will dilute the Sodium
        
        NOTE: Hyponatraemia also occurs in Secondary Hyperaldosteronism caused by a Renin-producing tumour
        
        Apparent Mineralocorticoid Excess
        Outline Apparent Mineralocorticoid Excess
        
        In Apparent Mineralocorticoid Excess, the Blood Pressure is Increased BUT it is Increased by something else NOT Renin or Aldosterone
        
        The Increase in Blood Pressure inhibits the secretion of Renin and Aldosterone
        
        Apparent Mineralocorticoid Excess mimics the presentation of Primary Hyperaldosteronism
        
        However, there is a Low Renin and a Low Plasma Aldosterone
        
        Apparent Mineralocorticoid Excess has the following presentation:
        
        Hypertension
        
        Mild Hypernatraemia
        
        Hypokalaemia
        
        Alkalosis (Increased HCO3-)
        
        Low Renin
        
        Low Plasma Aldosterone
        
        Causes of Apparent Mineralocorticoid Excess
        List the Causes of Apparent Mineralocorticoid Excess
        
        Apparent Mineralocorticoid Excess is caused by:
        
        Glucocorticoid Excess such as Cushing's Syndrome
        
        Defect of 11-Beta-Hydroxysteroid Dehydrogenase Type II Enzyme
        
        Liddle Syndrome
- - - - Causes of Excess Cortisol Production (Cushing's Syndrome)
        Outline the Causes of Excess Cortisol Production (Cushing's Syndrome)
        
        Excess Cortisol Production may be caused by issues in the Hypothalamus, Anterior Pituitary Gland or Adrenal Gland
        
        Excess Cortisol Production (Cushing's Syndrome) may be caused by a:
        
        Cortisol-producing Tumour (10%)
        
        Exogenous intake of Cortisol (10%)
        
        Tumour in the Pituitary Gland that produces excess Adrenocorticotropic Hormone (ACTH)
        
        This accounts for 90% of Cases of Excess Cortisol Production
        
        Determining the Cause of Excess Cortisol Production (Cushing's Syndrome)
        Describe how to Determine the Cause of Excess Cortisol Production (Cushing's Syndrome)
        
        When determining the Cause of Excess Cortisol Production the following needs to occur:
        
        Measure the Adrenocorticotropic Hormone (ACTH) Level at 8 am
        
        Pituitary Adenoma
        
        If the Elevated Cortisol levels are due to a Pituitary Adenoma the:
        
        Cortisol Levels will be elevated
        
        ACTH Levels will be Normal or Slightly Elevated
        
        Ectopic ACTH
        
        If the Elevated Cortisol levels are caused by the Ectopic production of ACTH the:
        
        Cortisol Levels will be elevated
        
        ACTH Levels will be elevated
        
        Adrenal Tumour
        
        If the Elevated Cortisol Levels are due to an Adrenal Tumour:
        
        Cortisol Levels will be elevated
        
        ACTH will be undetectable
        
        Mechanism of Action of Cortisol
        Describe the mechanism of Action of Cortisol
        
        Cortisol is a steroid hormone
        
        Cortisol is able to the Mineralocorticoid Receptor in the Nucleus inside the Renal Distal Tubular Cells
        
        However, Cortisol is inactivated by the 11-Beta-Hydroxysteroid Dehydrogenase Type II Enzyme
        
        Beta-11-Hydrosteroid Dehydrogenase Type II Enzyme converts the active form of Cortisol into is inactive form called Cortisone
        
        Cortisone is unable to bind to the Mineralocorticoid Receptor
        
        When there is Excess Cortisol production in the case of Cushing's Syndrome, the 11-Beta-Hydroxysteroid Dehydrogenase Type II Enzyme becomes saturated
        
        And excess Cortisol is free to bind the Mineralocorticoid Receptor
        
        This allows for the Increased expression of the Epithelial Sodium Channel (ENaC) on the Apical Membrane
        
        Increased expression of the Epithelial Sodium Channel (ENaC) results in an:
        
        Increased uptake of Sodium into the Kidney
        
        Equal Loss of Potassium and Hydrogen Ion in the Urine
        
        This results in Hypertension, Hypernatraemia, Hypokalemia and Alkalosis
        
        Defect of 11-Beta-Hydroxysteroid
        Dehydrogenase Type II Enzyme
        Describe the Defect of 11-Beta-Hydroxysteroid Dehydrogenase Type II Enzyme
        
        11-Beta-Hydroxysteroid Dehydrogenase Type II Enzyme is responsible for converting active Cortisol into an inactive form called Cortisone
        
        Cortisone is unable to bind to the Mineralocorticoid Receptor
        
        Therefore, a Defect of the 11-beta-Hydroxysteroid Dehydrogenase Enzyme means that Cortisol will remain active and bind to the Mineralocorticoid Receptor
        
        Therefore, causing Hypertension, Hypernatraemia, Hypokalaemia, and Alkalosis
        
        List the Causes of a Defect of the 11-B-Hydroxysteroid Dehydrogenase Type II Enzyme
        
        Defect of 11-Beta-Hydroxysteroid Dehydrogenase Type II Enzyme may be caused by:
        
        Genetic Mutation of 11-Beta-HSD
        
        Excess Licorice Intake
        
        Licorice contains Glycerrhizic Acid which inhibits the 11-Beta-HSD Type II Enzyme