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what is Addison’s disease? Give detail about aldosterone?

what is Addison’s disease? Give detail about aldosterone?

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A female patient presented to her physician appeared thin, with sunken eyes. She told her physician that she has lost 20 pounds, she faces extreme fatigue and she has not had a menstrual period in the last three months.

Recorded blood pressure was very low (70/35) and pulse rate increased 120 beats/min. Her skin was deeply pigmented especially at nipples and in the creases of the hands. Labs tests showed:

  • Decreased Na ions, increased potassium ions, decreased osmolality, decreased fasting glucose, decreased cortisol and aldosterone, and increased ACTH.

Based on the physical appearance and lab tests, what is your diagnosis, and what are the clinical features of the disease? Give details about biosynthesis of aldosterone, its mechanism of action, functions of aldosterone, and regulation of aldosterone?

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Diagnosis:

The patient has primary adrenal deficiency (Addison’s disease).

The adrenal gland consists of the adrenal cortex and adrenal medulla. The adrenal cortex has three layers; zona glomerulosa, zona fasciculata, and zona reticularis. Zona glomerulosa produces mineralocorticoid (aldosterone), zona fasciculata produces glucocorticoid (cortisol), and zona reticularis produces androgens. In Addison’s disease, there is adrenal insufficiency due to injury or atrophy of the adrenal cortex due to autoimmune disease or cancer invasion. The person with Addison's disease shows the following features:

Mineralocorticoid deficiency:

Due to the lack of aldosterone the patient has

  • Hyponatremia
  • Hyperkalemia
  • Mild acidosis
  • A decrease in the ECF volume.
  • Red blood concentration decreases.
  • Cardiac output and Blood pressure decrease.
  • Cardiac toxicity

If a patient with Addison’s disease is left untreated, the patient can die of shock.

Glucocorticoid deficiency:

Due to the loss of cortisol the person has the following features:

  • Hypoglycemia due to inability to maintain blood glucose and use proper metabolic products.
  • Fatigue
  • Muscles become week.
  • The person cannot tolerate stress.
  • Depression and other behavioral disorders.

Melanin pigmentation:

In Addison’s disease, there is no feedback inhibition of ACTH from the hypothalamus and pituitary which causes the excess Melanin stimulating hormone to be released from the anterior pituitary that causes the pigmentation of the skin and mucous membranes.

Biosynthesis of Aldosterone:

Aldosterone is a steroid hormone that is secreted by the zona golmerulosa of the cortex of the adrenal gland. It is the main mineralocorticoid secreted by zona glomerulosa. It is formed from cholesterol in the following way:

  • Cholesterol is converted to pregnenolone by the enzyme cholesterol desmolase.
  • 3beta-hydroxysteroid dehydrogenase converts Pregnenolone into progesterone.
  • Progesterone is converted into 11-deoxycorticosterone by the enzyme 21beta- hydroxylase.
  • 11-deoxycorticosterone is converted into corticosterone by the enzyme 11beta- hydroxylase.
  • Corticosterone is converted into Aldosterone by the enzyme Aldosterone synthase.

Image for question

Mechanism of action:

Aldosterone has two mechanisms of action. One is by interacting with the nucleus (DNA) and the other is Non-genomic action.

Genomic action:

Genomic action is slow and takes much time. Because aldosterone is a lipid-soluble molecule, it can easily cross the cell membrane and bind to the mineralocorticoid receptor in the cytoplasm of the cell. The aldosterone and mineralocorticoid receptor complex moves into the nucleus and binds to the DNA. This leads to the formation of many mRNAs through the transcription process. This mRNA diffuses into the cytoplasm where the protein machinery (ribosomes) makes several proteins through the translation process.

The proteins that are produced include enzymes and membrane transporters. One of the transporters is Sodium-potassium adenosine triphosphatase that carries three sodium ions out of the cells and two potassium ions into the cells. Another transporter is the epithelial sodium channel in the renal tubular cells.

Image for question

Non-genomic action:

Non-genomic action is fast and takes less time. The binding of aldosterone to cell membrane receptors leads to the production of a second messenger system. In renal epithelial cells and vascular smooth muscle cells, aldosterone increases the formation of cAMP (cyclic adenosine monophosphate). In some other cells, Aldosterone stimulates the phosphatidylinositol second messenger system.

Functions of aldosterone:

The functions of the aldosterone hormone are the following:

1.Aldosterone increases the reabsorption of sodium ions and causes the secretion of potassium ions from the renal tubular epithelial cells (principal cells in the collecting tubules and distal convoluted tubules). Deficiency of aldosterone leads to hyponatremia and hyperkalemia.

2.The sodium reabsorption from renal cells causes the osmotic reabsorption of water which causes an increase in the extracellular fluid volume.

3.Aldosterone causes an increase in arterial pressure which is due to the increased sodium and water reabsorption.

4.Aldosterone causes the reabsorption of sodium chloride in the sweat glands and salivary glands and causes the secretion of potassium and bicarbonate ions.

5.Aldosterone enhances sodium reabsorption by the intestines, especially the colon.

6.Aldosterone also causes the excretion of hydrogen ions in exchange for potassium ions in intercalated cells causing metabolic alkalosis.

Aldosterone escape:

The sodium ion is increased in extracellular fluid when aldosterone is secreted by the adrenal cortex. This is followed by an increase in the ECF volume. Excessive increase in the aldosterone that causes the increase in sodium ions in the extracellular fluid for 1 to 2 days leads to pressure natriuresis and pressure diuresis. This is because an increase in extracellular fluid (ECF) sodium results in increased extracellular fluid (ECF) volume and increased arterial pressure that leads to pressure natriuresis (increased excretion of sodium due to increased pressure) and pressure diuresis (increased excretion of water due to increased arterial pressure). This leads to the return of sodium and water excretion back to normal and the sodium absorbing effects of aldosterone are lost due to pressure natriuresis and diuresis. This is called aldosterone escape (the effect of aldosterone on sodium reabsorption is minimal).

Regulation of aldosterone:

Aldosterone is not regulated by the Adrenocorticotropic hormone of the anterior pituitary. It is regulated by the following factors.

1.Increased potassium ion concentration in the extracellular fluid leads to increased aldosterone secretion. (a potent regulatory factor)

2.Increased angiotensin 2 concentration (increased angiotensin 2 is because of decreased blood flow or loss of sodium ions) in the extracellular fluid leads to aldosterone secretion. (a potent regulatory factor).

3.Increased sodium in the extracellular fluid causes decreased secretion of aldosterone.

4.Adrenocorticotropic hormone (ACTH) has very little effect on aldosterone secretion.

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what is Addison’s disease? Give detail about aldosterone?

what is Addison’s disease? Give detail about aldosterone?

bounty icon
$50
Single winner
Asked  7 months ago
Viewed  0 times

A female patient presented to her physician appeared thin, with sunken eyes. She told her physician that she has lost 20 pounds, she faces extreme fatigue and she has not had a menstrual period in the last three months.

Recorded blood pressure was very low (70/35) and pulse rate increased 120 beats/min. Her skin was deeply pigmented especially at nipples and in the creases of the hands. Labs tests showed:

  • Decreased Na ions, increased potassium ions, decreased osmolality, decreased fasting glucose, decreased cortisol and aldosterone, and increased ACTH.

Based on the physical appearance and lab tests, what is your diagnosis, and what are the clinical features of the disease? Give details about biosynthesis of aldosterone, its mechanism of action, functions of aldosterone, and regulation of aldosterone?

  • add comment
avatar

Diagnosis:

The patient has primary adrenal deficiency (Addison’s disease).

The adrenal gland consists of the adrenal cortex and adrenal medulla. The adrenal cortex has three layers; zona glomerulosa, zona fasciculata, and zona reticularis. Zona glomerulosa produces mineralocorticoid (aldosterone), zona fasciculata produces glucocorticoid (cortisol), and zona reticularis produces androgens. In Addison’s disease, there is adrenal insufficiency due to injury or atrophy of the adrenal cortex due to autoimmune disease or cancer invasion. The person with Addison's disease shows the following features:

Mineralocorticoid deficiency:

Due to the lack of aldosterone the patient has

  • Hyponatremia
  • Hyperkalemia
  • Mild acidosis
  • A decrease in the ECF volume.
  • Red blood concentration decreases.
  • Cardiac output and Blood pressure decrease.
  • Cardiac toxicity

If a patient with Addison’s disease is left untreated, the patient can die of shock.

Glucocorticoid deficiency:

Due to the loss of cortisol the person has the following features:

  • Hypoglycemia due to inability to maintain blood glucose and use proper metabolic products.
  • Fatigue
  • Muscles become week.
  • The person cannot tolerate stress.
  • Depression and other behavioral disorders.

Melanin pigmentation:

In Addison’s disease, there is no feedback inhibition of ACTH from the hypothalamus and pituitary which causes the excess Melanin stimulating hormone to be released from the anterior pituitary that causes the pigmentation of the skin and mucous membranes.

Biosynthesis of Aldosterone:

Aldosterone is a steroid hormone that is secreted by the zona golmerulosa of the cortex of the adrenal gland. It is the main mineralocorticoid secreted by zona glomerulosa. It is formed from cholesterol in the following way:

  • Cholesterol is converted to pregnenolone by the enzyme cholesterol desmolase.
  • 3beta-hydroxysteroid dehydrogenase converts Pregnenolone into progesterone.
  • Progesterone is converted into 11-deoxycorticosterone by the enzyme 21beta- hydroxylase.
  • 11-deoxycorticosterone is converted into corticosterone by the enzyme 11beta- hydroxylase.
  • Corticosterone is converted into Aldosterone by the enzyme Aldosterone synthase.

Image for question

Mechanism of action:

Aldosterone has two mechanisms of action. One is by interacting with the nucleus (DNA) and the other is Non-genomic action.

Genomic action:

Genomic action is slow and takes much time. Because aldosterone is a lipid-soluble molecule, it can easily cross the cell membrane and bind to the mineralocorticoid receptor in the cytoplasm of the cell. The aldosterone and mineralocorticoid receptor complex moves into the nucleus and binds to the DNA. This leads to the formation of many mRNAs through the transcription process. This mRNA diffuses into the cytoplasm where the protein machinery (ribosomes) makes several proteins through the translation process.

The proteins that are produced include enzymes and membrane transporters. One of the transporters is Sodium-potassium adenosine triphosphatase that carries three sodium ions out of the cells and two potassium ions into the cells. Another transporter is the epithelial sodium channel in the renal tubular cells.

Image for question

Non-genomic action:

Non-genomic action is fast and takes less time. The binding of aldosterone to cell membrane receptors leads to the production of a second messenger system. In renal epithelial cells and vascular smooth muscle cells, aldosterone increases the formation of cAMP (cyclic adenosine monophosphate). In some other cells, Aldosterone stimulates the phosphatidylinositol second messenger system.

Functions of aldosterone:

The functions of the aldosterone hormone are the following:

1.Aldosterone increases the reabsorption of sodium ions and causes the secretion of potassium ions from the renal tubular epithelial cells (principal cells in the collecting tubules and distal convoluted tubules). Deficiency of aldosterone leads to hyponatremia and hyperkalemia.

2.The sodium reabsorption from renal cells causes the osmotic reabsorption of water which causes an increase in the extracellular fluid volume.

3.Aldosterone causes an increase in arterial pressure which is due to the increased sodium and water reabsorption.

4.Aldosterone causes the reabsorption of sodium chloride in the sweat glands and salivary glands and causes the secretion of potassium and bicarbonate ions.

5.Aldosterone enhances sodium reabsorption by the intestines, especially the colon.

6.Aldosterone also causes the excretion of hydrogen ions in exchange for potassium ions in intercalated cells causing metabolic alkalosis.

Aldosterone escape:

The sodium ion is increased in extracellular fluid when aldosterone is secreted by the adrenal cortex. This is followed by an increase in the ECF volume. Excessive increase in the aldosterone that causes the increase in sodium ions in the extracellular fluid for 1 to 2 days leads to pressure natriuresis and pressure diuresis. This is because an increase in extracellular fluid (ECF) sodium results in increased extracellular fluid (ECF) volume and increased arterial pressure that leads to pressure natriuresis (increased excretion of sodium due to increased pressure) and pressure diuresis (increased excretion of water due to increased arterial pressure). This leads to the return of sodium and water excretion back to normal and the sodium absorbing effects of aldosterone are lost due to pressure natriuresis and diuresis. This is called aldosterone escape (the effect of aldosterone on sodium reabsorption is minimal).

Regulation of aldosterone:

Aldosterone is not regulated by the Adrenocorticotropic hormone of the anterior pituitary. It is regulated by the following factors.

1.Increased potassium ion concentration in the extracellular fluid leads to increased aldosterone secretion. (a potent regulatory factor)

2.Increased angiotensin 2 concentration (increased angiotensin 2 is because of decreased blood flow or loss of sodium ions) in the extracellular fluid leads to aldosterone secretion. (a potent regulatory factor).

3.Increased sodium in the extracellular fluid causes decreased secretion of aldosterone.

4.Adrenocorticotropic hormone (ACTH) has very little effect on aldosterone secretion.

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