Physiology Lecture 8 - 9/13/11

Physician Assistant Pha 529 with Steffes at Methodist College

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By: Rachel Enigk
Created: 2011-09-14
Size: 56 flashcards
Views: 68

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What are the two main causes of Primary Hyperaldosteronism?

Unilateral adrenocortical adenoma of the zona glomerulosa (Conn’s syndrome) 73%
Bilateral cortical hyperplasia (27%)

What percent of unilateral adrenocortical adenomas of the zona glomerulosa are benign?

98%

only 2% are malignant

This is one of the causes of primary hyperaldosteronism

Describe the nature of bilateral cortical hyperplasia (cause of primary hypoaldosteronism in 27%of cases).

Typically not caused by a distinct tumor, but rather the cortical region is just very enlarged.

How can you determine if a patient has suppressible vs. non-suppressible primary hyperaldosteronism?

If you give cortisol to a suppressible patient, it should shut off ACTH production.

However, for most patients with this disorder, giving cortisol will NOT cause ACTH levels to drop (the non-suppressible form of the disorder)

Primary hyperaldosteronism is responsible for 0.7% of _________ cases, primarily in women.

hypertension

This is an easily curable form of hypertension because the underlying cause is clear.

Most endocrine disorders are more common in ________ except for testicular disorders.

Women

Symptoms of Primary Hyperaldosteronism

Mild to moderate hypertension, muscular weakness due to hypokalemia (sometimes with periods of near-paralysis - potassium is dangerously low), paresthesias with tetany, headache, polyuria and polydipsia. Edema is rare (because fluid is intravascular)

Typically women in their 30s, 40s, overweight

May have muscle cramps

(not a definition - just a picture I inserted for understanding)

List the Preliminary Lab Findings for Primary Hyperaldosteronism - from initial screening labs

Hypokalemia - most common finding

Hypernatremia - sodium may be only mildly elevated or even normal (sodium is high but retention of fluid balances it out)

Metabolic alkalosis – due to the potassium depletion decreasing the concentrating ability of the kidneys (polyuria)

List the diagnostic lab findings for Primary Hyperaldosteronism (4)

Low plasma renin (normal or high renin EXCLUDES primary hypoaldosteronism as a diagnosis)
High aldosterone

Together, these results confirm primary hypoaldosteronism

Also:

24 hour urinary aldosterone - raised in primary disease

CAT scan to differentiate between tumor and hyperplasia

A normal patient who assumes a standing position will have a drop in blood pressure and therefore a marked increase in _______ levels.

Renin

So, effect of posture on renin should be considered - patient should be lying down when level is drawn and it should be early morning.

What is a useful test for differentiating the two types of primary hyperaldosteronism?

Check plasma aldosterone concentration (PAC) both while the patient is standing and while they are laying down.

A patient with a unilateral adenoma won't show a change between the two PAC values.

A patient with bilateral adrenal hyperplasia will show a PAC increase while standing.

Treatment for primary hyperaldosteronism - unilateral adenoma

Laparoscopic adrenalectomy or life-long spironolactone (specific aldosterone antagonist)

Literally a one-day cure

Spironolactone - competitive inhibitor - blocks the receptors - you have to taper it upward

Treatment for primary hyperaldosteronism - bilateral adrenal hyperplasia

Life-long spirolactone

Characteristics of Secondary Hyperaldosteronism

Intact renin-angiotensin-aldosterone mechanism but there is a chronic stimulation (and/or diminished metabolism)

Typically, something is producing too much renin

Or, there is a chronic metabolism problem - i.e. cirrhosis of the liver

Partial list of causes of Secondary Hyperaldosteronism

Diuretic therapy

Accelerated hypertension

CHF - congestive heart failure

Nephrotic Syndrome

Liver cirrhosis with ascites

Renal artery stenosis

- Essentially, anything that causes hypovolemia, low blood pressure, decreased blood flow because this will lead to decreased profusion of the kidney.

Treatment of Secondary Hyperaldosteronism

Treat the condition that caused it - i.e. stop diuretic therapy, hypertension, nephrotic syndrome, etc

Characteristics of hypoaldosteronism

Excessive loss of sodium leading to hypovolemia

Hypotension

Increased plasma renin activity

Hyperkalemia

Mild acidosis

Function of Glucocorticoids

95% of glucocorticoid function is from cortisol

Cortisol mediates most effects by binding with intracellular receptors in target tissues and inducing (or repressing) gene transcription resulting in enzymes that alter cell function

Glucocorticoid (mostly cortisol) effects on metabolism

Decreases protein stores outside of the liver

Tends to increase blood glucose concentration

Mobilizes fatty acids from adipose tissue

Resistance to stress

Does cortisol always have a direct effect?

No - some of its effects are permissive in nature. It must be present for other functions to proceed.

How does cortisol affect protein in extrahepatic (outside of the liver) tissues?

Decreases protein stores outside of the liver

Decreased amino acid uptake

Inhibits protein synthesis

Catabolic and anti-anabolic (breaks it down and stops the process of building it back up)

Cortisol causes the break-down of proteins. The elevation in levels of amino acids promotes _________.

gluconeogenesis

Tends to cause increased blood glucose concentration

Increased gluconeogenesis stimulates glycogen formation

Anti-insulin effect impairing utilization of glucose in the periphery

Mostly in muscle and adipose tissue

Diabetogenic (like GH)

What is the nature of the effect of cortisol on fatty acid mobilization?

Permissive effect on the lipolysis caused by epinephrine and growth hormone during starvation.

Doesn't have a direct effect, but allows this to take place.

If we don't have cortisol....

our bodies couldn't handle significant stress and we would "literally fall over and die."

If you have a patient who's been on steroids in the last year, their ACTH-cortisol system will be suppressed and they may not handle the stress of an operation well.

What are the anti-inflammatory effects of glucocorticoids?

Anti-inflammatory and anti-allergic effects; suppression of immune responses

Stabilization of lysosomal membranes decreasing the release of proteolytic enzymes by damaged cells

Suppression of the immune system – decreased production of T cells and antibodies

Inhibition of fibroblastic activity

Anti-lymphoma - steroids kill white cell

Anti-inflammatory and anti-allergic effects; suppression of immune responses

Inhibition of phospholipase

Decreases the synthesis of arachidonic acid

Arachnidonic acid is the precursor of many mediators of local inflammatory response (dilation of capillaries, increased capillary permeability and migration of leukocytes into the injured tissue)

Arachnidonic acid and its derivates

Arachnidonic acid is the precursor of many mediators of local inflammatory response (dilation of capillaries, increased capillary permeability and migration of leukocytes into the injured tissue)

Leukotrienes

Prostaglandins

Thromboxanes

Details of glucocorticoid inhibition of fibroblastic activity

Wound-healing process falls apart

Risk of hernia formation

Some is a result of the stabilization of lysosomal membranes

Vitamin A in large doses can counter-balance this lysosomal effect

Must be prior to the operation

ACTH release is dependent on the hypophysiotropic hormone _____.

CRH - corticotropin releasing hormone - from the hypothalamus

What 2 zones of the adrenals are most commonly affected by ACTH?

What happens when these 2 zones are chronically stimulated?

zona fasciculata (mostly) and zona reticularis

Chronic stimulation causes hypertrophy and hyperplasia of these two zones

Chronic stimulation causes continued increased synthesis of several enzymes that metabolize cholesterol, promoting chronic increased secretion of cortisol and adrenal androgens

Chronic stimulation of the zona fasciculata and zona reticularis leads to increased synthesis of enzymes that metabolize cholesterol. Which enzyme was given as an example in class? What is its secondary messenger?

Cholesterol desmolase, promoted by the secondary messenger cAMP

Plasma ________ (free, unbound) inhibits ACTH release and has a indirect inhibition of the CRH release.

cortisol

How is ACTH secretion affected by circadian rhythms?

The frequency and duration of CRH burst from the hypothalamus varies by time of day (and therefore the release of ACTH also varies)

Highest in early morning and lowest in late evening

So, you understand a patient's "normal" level based on standard lab values and the time of day.

This is most important for high levels, because they can vary - really low levels are always bad

Stress increases ________ secretion by over-riding the normally negative inhibitory effect of cortisol.

ACTH

Potential causes of Cushing's Syndrome and Cushing's Disease

Adrenal tumor of the zona fasciculata

Pituitary tumor producing ACTH and resultant bilateral adrenal hyperplasia (Cushing’s disease)

- And it's ONLY called Cushing's disease when there is a pituitary adenoma

Ectopic production of ACTH from tumor

- Can be true ACTH or can be a ACTH-like

Iatrogenic administration of steroids

- We are responsible for most cases of Cushing's

Symptoms of Cushing's Syndrome/Disease

Centripetal fat distribution

Mobilization of fat from the extremities to the abdomen, face (“Moon face”) and supraclavicular areas.

Fat in the upper back/lower neck gives a characteristic “buffalo hump”

Hypertension and hypokalemia

Protein depletion

Abnormal calcium metabolism

What the associated symptoms of the hypertension and hyperkalemia caused by Cushing's?

High plasma levels of cortisol (the weak mineralocorticoid effect is increased by the increased concentration)

High plasma levels of 11-deoxycorticosterone if being secrete

Hypokalemia is very likely

What symptoms result from the protein depletion caused by Cushing's?

Muscle weakness

Loss of connective tissue

Thinned skin (striae) - stretch marks

Impaired growth in children

Impaired response to infections due to suppression of immune system

Impaired carbohydrate metabolism, hyperglycemia and insulin-resistant diabetes mellitus

Masculinizing affects if adrenal androgens are secreted in excess

Cataracts (affects protein metabolism in eyes)

What are the associated symptoms of the abnormal calcium metabolism caused by Cushing's?

Osteoporosis and vertebral fractures due to protein depletion (bony matrix decreased)

If this happens to an older person, you can have severe and frequent fractures

Abnormal calcium absorption from the gut (anti–Vitamin D activity) and increased glomerular filtration rate and renal excretion of calcium

Your body tries to get rid of it, in addition to not being able to use it

What is Addison's disease?

Adrenal cortical insufficiency

What are some potential causes of Addison's disease?

Causes of the cortical destruction include autoimmune disease (80% in the US), TB, cancer, sarcoidosis, adrenal hemorrhage (post-partum, DIC) and other more rare causes.

Symptoms of Addison's Disease

Symptoms are those of hypoaldosteronism combined with those of glucocorticoid deficiency.

Vague symptoms including fatigability, mental irritability, psychological changes, and nausea are sometimes prominent. Hypotension and orthostatic changes are common.

The resultant high ACTH level produces hyperpigmentation (via the MSH activity of ACTH) of all areas (lines, creases, nipples, genitals).

Aldosterone deficiency

Glucocorticoid deficiency

What are the symptoms associated with aldosterone deficiency caused by Addison's disease?

There is excessive loss of sodium with resultant hypovolemia, hypotension and increased plasma renin activity

There is excessive potassium retention (hyperkalemia)

Mild acidosis

What are the symptoms associated with glucocorticoid deficiency caused by Addison's disease?

Muscle weakness, fasting hypoglycemia and impaired fat utilization for energy

Loss of appetite and weight loss

Poor tolerance to stress can lead to Addisonian crisis.

BP drops, heart fails to pump, brain trouble, seizures

Screening labs for Addison's disease

In chronic conditions, low sodium (90%) and high potassium (65%) are most common

May have hypoglycemia

- Particularly when stressed

Hypercalcemia may be present

- Depending on the effect on bone metabolism/anti-vitamin D

Diagnostic labs for Addison's disease

Low plasma cortisol at 8:00 AM is diagnostic, especially if associated with an elevated ACTH level

Serum DHEA levels are under 1000 ng/ml (100% have insufficient androgen levels) - this is one of the most distinct labs for diagnosing Addison's

15% of normals (usually the children and aged) have similar levels

Elevated renin level

Antiadrenal antibodies ~50% of autoimmune cases – not particularly helpful

Treatment of Addison's disease

Hydrocortisone is drug of choice because of its combined glucocorticoid and mineralocorticoid effect

If there is not enough mineralocorticoid effect, then use fludrocortisone acetate.

- Has a profound mineralocorticoid effect, but can be expensive and occasionally hard to monitor

DHEA supplementation is of help for some women

What is "adrenal fatigue"?

A fake disease promoted by www.adrenalfatigue.org to promote some doctor's book.

What are the two types of adrenogential syndrome?

Masculinizing adrenocortical tumor

Congenital Adrenal Hyerplasia

Describe a masculinizing adrenocortical tumor

Causes one type of adrenogenital syndrome

If you have a tumor that produces too many androgens, obviously it's going to be masculinizing

Women grow beards

In adult female: Hirsutism (including beard), deeper voice, baldness (if genetically inclined), growth of the clitoris to resemble a penis, male muscle and body distribution pattern

In prepubertal males and females: penile maturation or clitoral hypertrophy, early onset of masculine pubertal findings

Describe congenital adrenal hyperplasia

Congenital adrenal hyperplasia is a metabolic disorder related to enzymatic defects in the biosynthesis of cortical steroids.

Typically the defects are inherited in an autosomal recessive manner, and within a particular family all inherit the same enzyme deficiency.

Two principal effects result from the enzyme deficiency:

deficient cortisol and/or aldosterone production
excess precursor steroids

Effect of congenital adrenal hyperplasia on children

The enlargement of the clitoris can be such that there is genital ambiguity (i.e. the right sex is uncertain on exam). The male penis will show marked early maturation. These children usually have rapid growth, but with the closure of epiphyseal plates, they are short as adults

At least eight distinctive clinical syndromes of congential adrenal hyperplasia are recognized but the majority of cases are attributed to:

21-hydroxylase deficiency (95%)

11-beta-hydroxylase deficiency (5%)

One of the effects of congenital adrenal hyperplasia is an increase in precursor steroids. How does the body respond to this?

In response, there is increased ACTH secretion from the anterior pituitary producing adrenocortical hyperplasia. This hormone in turn causes the adrenal glands to overproduce certain intermediary hormones which have testosterone-like effects on the fetus and child, leading to so-called “virilization”.

When they are born, the look very masculinized

About this deck

By: Rachel Enigk
Created: 2011-09-14
Size: 56 flashcards
Views: 68

About StudyBlue

“Simply amazing. The flash cards are smooth, there are many different types of studying tools, and there is a great search engine. I praise you on the awesomeness.”
Dennis