Parathyroid Gland to Adrenal Gland

Parathyroid Gland

❖ Regulate calcium levels

❖ Produced if there is a decreased calcium

❖ Parathyroid gland produces parathyroid hormone

It is located on or near the thyroid capsule (region of the thyroid gland) sometimes within the thyroid

gland

 It may also be found outside their normal anatomic site – between the hyoid bone in the neck and

mediastinum

 Most people have 4 parathyroid glands but some have 8 or as few as 2

 Smallest endocrine gland in the body

1. Parathyroid Hormone

 Parathyroid hormone (PTH), parathormone or parathyrin, is secreted by the chief cells of

the parathyroid glands as a polypeptide containing 84amino acids.

 It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone

produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration.

(hypercalcemic hormone) – if calcium levels decrease, PTH is released

 Preserves calcium and phosphate within normal range

 PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone

receptor in three parts of the body

 Promotes bone resorption

 Stimulates conversion of inactive vitamin D to activated vitamin D3

 Indirectly stimulates intestinal absorption of calcium

 PTH half-life is approximately 4 minutes. It has a molecular mass of 9.4 kDa.

■ PTH - increase calcium levels; extract through the bone through osteoclasts

Functions

A. Regulation of serum calcium

Parathyroid hormone regulates serum calcium through its effects on the following tissues:

B. Regulation of serum phosphate

PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney which means more

phosphate is excreted through the urine.

However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone,

slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, which is

mediated by an increase in activated vitamin D, the absorption of phosphate is not as dependent on vitamin D

as is that of calcium. The end result is a small net drop in the serum concentration of phosphate.

C. Vitamin D synthesis

PTH increases the activity of 1-α-hydroxylase enzyme, which converts 25-hydroxycholecalciferol to 1,25-

dihydroxycholecalciferol, the active form of vitamin D.

Stimulators

 Decreased serum [Ca2+].

 Mild decreases in serum [Mg2+].

 An increase in serum phosphate (increased phosphate causes it to complex with serum calcium,

forming calcium phosphate, which reduces stimulation of Ca-sensitive receptors (CaSr) that do not

sense Calcium phosphate, triggering an increase in PTH)

Inhibitors

 Increased serum [Ca2+].

 Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such

as hypocalcemia)

Clinical Disorders:

1. Hyperparathyroidism

a. Primary Hyperparathyroidism (physiologic effect lies with the PT gland)

 Most common cause of hypercalcemia

 Due to the presence of a functioning parathyroid adenoma

 Accompanied with phosphaturia

 If it is undetected, severe demineralization may occur

b. Secondary Hyperparathyroidism

 Develops in response to serum calcium

 There is diffuse hyperplasia of all 4 glands

 The patient develops severe bone disease

 Causes: vitamin D deficiency and chronic renal failure

c. Tertiary Hyperparathyroidism

 It occurs when patients with secondary hyperparathyroidism

 Develop autonomous function of the hyperplastic parathyroid glands or of a parathyroid

adenoma

 The phosphate levels are normal to high; calcium phosphates in soft tissue

2. Hypoparathyroisim

 Due to accidental injury to the PT glands during thyroid or neck surgery, removal of the glands with

thyroid glands, or idiopathic atrophy

 Other cause: autoimmune parathyroid destruction

 Individuals are unable to maintain calcium concentration in blood without calcium supplementation

■ Osteoclasts digest bone to produce ionized calcium in the

bloodstream

❖ Kidneys: PTH prevents removal of calcium

■ Activates Renal-1-alpha hydrolase

❖ Endocrine gland: Parathyroid gland - regulation of calcium

❖ Hypercalcemia - ↑ blood calcium is high

■ Parathyroid gland won’t do anything

■ Hormone: Calcitonin - produced by thyroid gland - facilitates entry

❖ Hypocalcemia - ↓ blood calcium is low

■ Parathyroid gland will work to produce PTH (parathyroid hormone)

■ PTH -goes to the bone and kidney

◆ PTH in bone- stimulates osteoclast activity (macrophage of the

bone) to digest bone matrix

● Calcium and phosphate from bone is released to the blood

◆ PTH in kidney - very low threshold in the kidneys; Filtered out by

glomerulus

● Reabsorbed by the tubules

● Phosphates are excreted

● Activation of renal-1 hydroxylase (1-alpha-hydroxylase)

enzyme of the kidney (activates vit D)

● Vit D inactive - 25-hydroxycholecalciferol --> activated

1,25-dihydroxycholecalciferol

● Cholecalciferol - maintains calcium and increase calcium

■ In kidneys - promotes renal absorption of Ca2+

and reabsorb phosphate

Intestine - dietary intake absorption of Ca2+ and

Phosphate

■ Once absorbed, needs to bind with collagen for

the bone matrix

Located on top of the kidneys

❖ Medulla (inner part)

■ Epinephrine - adrenaline increase work output; increases amount of

Energy

HORMONES PRODUCED BY THE ADRENAL GLAND

Adrenal Gland

 Also known as suprarenal glands are endocrine glands that sit atop the kidneys; in humans, the right

suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped

 It is composed of distinct but conjoined glands, the outer adrenal cortex (yellow) and the inner adrenal

medulla (dark mahogany)

 They are chiefly responsible for releasing hormones in response to stress through

the synthesis of corticosteroids such as cortisol and catecholamines such as epinephrine.

 The adrenal glands affect kidney function through the secretion of aldosterone, a hormone involved in

regulating the osmolarity of blood plasma.

ADRENAL CORTEX

 Outer region of the adrenal gland secreting the steroid hormone

 Major site of steroid hormone production

1. Mineralocorticoids

 They are produced in the zona glomerulosa.

 The primary mineralocorticoid is aldosterone (most potent – electro regulating hormone).

 Its secretion is regulated by the oligopeptide angiotensin II (angiotensin II is regulated by angiotensin I,

which in turn is regulated by renin).

 Aldosterone is secreted in response to high extracellular potassium levels, low

extracellular sodium levels, and low fluid levels and blood volume.

 Aldosterone affects metabolism in different ways:

o It increases urinary excretion of potassium ions

o It increases interstitial levels of sodium ions

o It increases water retention and blood volume

Clinical Disorders:

 Primary hyperaldosteronism (Conn’s disease)

 Caused by Aldosterone-secreting adrenal adenoma

 Symptoms: HPN, hypokalemia, mild hypernatremia and metabolic alkalosis

 Secondary hyperaldosteronism

 Occurs as a result of excessive production of rennin

o Liddle’s syndrome (pseudohyperaldosteronism) – resembles primary aldosteronism

clinically but aldosterone level is low and absence of HPN

o Bartter’s syndrome (Bumetanide-sensitive chloride channel mutation) – elevated

concentrations of Aldosterone and rennin

o Gitelman’s syndrome (Thiazide-sensitive transporter mutation) – increased

aldosterone

 Hypoaldosteronism

 Due to destruction of the adrenal glands and deficiency of glucocorticoid

 It is also associated with enzyme 21-hydroxylase deficiency.

 Symptoms: hyperkalemia and metabolic acidosis

2. Glucocorticoids

 They are produced in the zona fasciculata.

 The primary glucocorticoid released by the adrenal gland in the human is cortisol and corticosterone in

many other animals.

 Its secretion is regulated by the hormone ACTH from the anterior pituitary.

 Secretion is diurnal and is associated with a person’s sleep-wake cycle.

o High level in the early morning (6-8AM) and lowest at night (10PM-12AM)

 Upon binding to its target, cortisol enhances metabolism in several ways:

o It stimulates the release of amino acids from the body

o It stimulates lipolysis, the breakdown of fat

o It stimulates gluconeogenesis, the production of glucose from newly released amino acids

and lipids – resulting in hyperglycemia (anti-insulin effect)

o It increases blood glucose levels in response to stress, by inhibiting glucose uptake

into muscle and fat cells

o It strengthens cardiac muscle contractions

o It increases water retention

o It has anti-inflammatory and anti-allergic effects

Clinical Disorders:

 Hypercorticolism (Cushing’s syndrome)

o Is cause primarily by excessive production of cortisol and ACTH

o S/S: weight gain but with thin extremities (buffalo hump), hyperglycemia, thinning of the skin,

poor wound healing, HPN, decreased WBC

 Hypocorticolism

o Primary Hypocorticolism (Primary Adrenal Insufficiency)

 Due to decreased cortisol production – 90% destruction of the adrenal cortex,

Aldosterone deficiency, excess ACTH release

 Disorders: Addison’s disease – hypotension, Hyponatremia, hyperkalemia,

hyperpigmentation and darkening of the skin.

o Secondary and Tertiary Hypocorticolism

 Due to hypothalamic-pituitary insufficiency with loss of ACTH

 No problem with mineralocorticoid secretion; absence of hyperpigmentation

3. Androgens

 They are produced in the zona reticularis.

 Produce as by-product of cortical synthesis that are regulated by ACTH

 They circulate bound to steroid hormone binding globulin (SHBG)

 The most important androgens include:

o Testosterone: a hormone with a wide variety of effects, ranging from enhancing muscle mass

and stimulation of cell growth to the development of the secondary sex characteristics.

o Dihydrotestosterone (DHT): a metabolite of testosterone, and a more potent androgen than

testosterone in that it binds more strongly to androgen receptors.

o Androstenedione (Andro): an androgenic steroid produced by the testes, adrenal cortex,

and ovaries. While androstenediones are converted metabolically to testosterone and

other androgens, they are also the parent structure of estrone.

o Dehydroepiandrosterone (DHEA): It is the primary precursor of natural estrogens. DHEA is also called dehydroisoandrosterone or dehydroandrosterone. The reticularis also produces DHEAsulfatedue to the actions of a sulfotransferase, SULT2A1

HORMONES PRODUCED BY ADRENAL MEDULLA

 The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex.

 It is the innermost part of the adrenal gland, consisting of cells that.

secrete epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine in

response to stimulation by sympathetic preganglionic neurons.

 Composed mainly of hormone-producing chromaffin cells, the adrenal medulla is the principal site of

the conversion of the amino acid tyrosine into the catecholamines epinephrine, norepinephrine, and

dopamine.

1. EPINEPHRINE (Adrenaline / Secondary Amine)

 Is a hormone and a neurotransmitter.

 Most abundant medullary hormone

 Called the “flight and fright hormone” because it is released in response to physiologic (injuries) or

psychological (stress, anxiety) threats

 Any form of stress that increases cortisol levels stimulates its production.

 It increases glucose concentration (glycogenolysis)

 Functions:

o increases heart rate

o constricts blood vessels

o dilates air passages and participates in the fight-or-flight response of the sympathetic nervous

system

 Chemically, epinephrine is a catecholamine, a monoamine produced only by the adrenal glands from

the amino acids phenylalanine and tyrosine.

 The term adrenaline is derived from the Latin roots ad- and renes and literally means "on the kidney",

in reference to the adrenal gland's anatomic location on the kidney.

 The Greek roots epi and nephros have similar meanings and give rise to epinephrine. The

term epinephrine is often shortened to epi.

2. NOREPINEPHRINE (Noradrenaline / Primary Amine)

 Is a catecholamine with multiple roles including as a hormone and a neurotransmitter.

 Areas of the body that produce or are affected by norepinephrine are described as noradrenergic.

One of the most important functions of norepinephrine is its role as the neurotransmitter released from the sympathetic neurons affecting the heart. An increase in norepinephrine from the sympathetic nervous system increases the rate of contractions.

As a stress hormone, norepinephrine affects parts of the brain, such as the amygdala, where attention and responses are controlled.

 Along with epinephrine, norepinephrine also underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle. It increases the brain's oxygen supply.

 Norepinephrine can also suppress neuroinflammation when released diffusely in the brain from the locus coeruleus.

 When norepinephrine acts as a drug it increases blood pressure by increasing vascular tone throughα-adrenergic receptor activation. The resulting increase in vascular resistance triggers compensatory reflex that overcomes its direct stimulatory effects on the heart, called the baroreceptor reflex, which results in a drop-in heart rate called reflex bradycardia.

 Norepinephrine is synthesized from dopamine-by-dopamine β-hydroxylase.

 It is released from the adrenal medulla into the blood as a hormone and is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons in the locus coeruleus.

 The actions of norepinephrine are carried out via the binding to adrenergic receptors.

3. DOPAMINE

 A catecholamine produced in the body by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA)  Present in highest concentration in the regions of the brain.

4. ENKEPHALIN

 Produced by the chromaffin cells.

 Regulates pain.

Clinical Disorders:

 Pheochromocytoma

o Tumors of the adrenal medulla or sympathetic ganglia

o Commonly seen in 3^rd to 5th decades of life

o Due to overproduction of catecholamines

o Tachycardia, headache, tightness of chess, sweating and pallor  Neuroblastoma

o A fatal malignant condition in children resulting to excessive production of norepinephrine

◆ Triggered by extreme stress

■ Norepinephrine - rest - antagonist of epinephrine/adrenaline

◆ Self-preservation mechanism

■ Dopamine - cause vasodilation, relaxing blood vessels

❖ Cortex (GFR- top to bottom) (outer membrane)

■ Zona glomerulosa (Aldosterone) - salt/sodium level

■ Zona fasciculata (Cortisol) - carbohydrate metabolism

■ Zona reticularis (Androgen - dehydroepiandrosterone) - secondary

sex characteristics

◆ Male has higher androgen levels

◆ Hematopoietic in nature.