Pathophysiology Exam 4

Endocrine and Nervous System Disorders

Major endocrine glands include:

1. Hypothalamus
2. Pituitary gland (hypophysis)
3. Pineal gland
4. Two adrenal glands
5. Thyroid gland
6. Four parathyroid glands
Endocrine portion of the:
7. Pancreas
8. Gonads
9. Thymus

What happens when endocrine glands secrete hormones?

1. Endocrine Glands secrete hormones into the interstitial fluid where they diffuse into the blood.
2. The hormones circulate to target cells in other glands or tissues.
3. After acting on the receptors on or in the target cells, the hormones are metabolized or inactivated by the target tissues or the liver and excreted by the kidneys to prevent excessive amounts from accumulating in the body.

Hormones:

Chemical messengers.

What do hormones operate on?

Hormones operate within feedback systems in which their release is stimulated or inhibited by blood levels of hormones, ions/nutrients, or by the nervous system.

What hormones originate from the Posterior Pituitary?

1. Antidiuretic Hormone ADH (Vasopressin)
2. Oxytocin

What hormones originate from the Anterior Pituitary?

1. Adrenocorticotropic Hormone (ACTH)
2. Thyroid-Stimulating Hormone (TSH)
3. Growth Hormone (GH)
4. Follicle-Stimulating hormone (FSH)
5. Luteinizing Hormone (LH)
6. Prolactin

Tropic Hormone:

Hormones from the anterior pituitary that cause growth and synthesis of hormones from other endocrine glands.

What are the tropic hormones?

1. ACTH
2. TSH
3. FSH
4. LH

What hormones originate from the Thyroid Gland?

T3 and T4

What hormones originate from the Adrenal Cortex?

1. Cortisol
2. Aldosterone

What hormones originate from the Adrenal Medulla?

1. Epinephrine

What hormones originate from the Parathyroid Glands?

Parathyroid Hormone (PTH)

What hormones originate from the Pancreas?

1. Insulin
2. Glucagon

ADH Primary Effects:

1. Increases reabsorption of water in kidney collecting ducts.
2. At high concentrations (ex: during hemorrhage) ADH causes vasoconstriction of peripheral vessels which results in increased BP.

ADH Effect.
-How does it increase the reabsorption of water in the kidney?
-What is its effect?

By causing the insertion of aquaporins. Which will:
1. Increase blood volume
2. Lower blood osmolality
3. Decrease urine output
4. Increase urine osmolality

Oxytocin Primary Effects:

1. Promotes "let down" milk reflex in lactating women.
2. Released in response to positive feedback at childbirth

What is the positive feeback factor causing the release of Oxytocin during childbirth?

Cervical stretch (from the baby's head) causes the release of oxytocin which promotes uterine contraction and cervical stretch.

ACTH Primary Effect:

Stimulates adrenal cortex to secrete primarily cortisol

TSH Primary Effect:

Stimulates thyroid gland.

GH Primary Effect:

Stimulates protein synthesis, stimulate tissue growth and metabolism.

FSH Primary Effect:

Women: Stimulates growth of ovarian follicles and estrogen secretion
Men: stimulates sperm production

LH Primary Effect:

Women: Stimulates maturation of ovum and ovulation; Men: Stimulates secretion of testosterone

Prolactin Primary Effect:

Stimulates growth of mammary glands and breast milk production during lactation.

T3 and T4 Hormones.
-What are they necessary for?
-What are its main targets?

-Necessary for growth and development in children including mental development and sexual maturity. Actions Include:
1. Metabolic Rate
2. Cardiorespiratory Function
3. Gastrointestinal
4. Neuromuscular

T3 and T4.
Metabolic Rate Primary Effects:

1. Increased metabolism of all body tissues/cells except retinas, spleen, testes & lungs.
2. Increased mobilization and metabolism of glucose, fat, protein, and increased heat and energy production.

T3 and T4.
Cardiorespiratory Primary Effects:

1. Increased oxygen consumption and metabolic end products.
2. Systemic vasodilation and increased blood flow to the skin (releases heat).
3. Increased blood volume, HR, contractility, SV & CO (BP constant due to vasodilation in skin).

T3 and T4.
Gastrointestinal Primary Effects:

1. Increased motility and gastrointestinal secretions.
2. Increased appetite.

T3 and T4.
Neuromuscular Primary Effect:

1. Increased muscle tone.
2. Normal brain development in the infant.
3. Increased sympathetic tone (permissive effect with catecholamines).

Cortisol Primary Effects:

1. Exerts anti-inflammatory effects and decreases immune response
2. Catabolic effect on tissues
3. Stress response

Aldosterone Primary Effects:

Increases sodium and water reabsorption in the kidney.

Epinephrine Primary Effects:

1. Stress response
2. Visceral and cutaneous vasoconstriction
3. Vasodilation in skeletal muscle
4. Increases rate and force of heart contraction
5. Bronchodilation

PTH Primary Effect:

Increases blood calcium levels.

How does PTH increase blood calcium levels?

1) Stimulating bone demineralization by activating osteoclasts to breakdown bone and release Ca2+ (and PO4-) into the blood
2) Ca2+ reabsorption (and PO4- secretion) from the kidney tubules
3) Activation of vitamin D by the kidneys which alllows for increased Ca2+ absorption from the intestine.

PIC: PTH Control and Function

Insulin Primary Effect:

Transport of glucose and other substances into cells
Lowers blood glucose level

Glucagon Primary Effect:

1. Glycogenolysis in liver
2. Increases blood glucose level

What is the release of hormones from glands controlled by?

1. Negative feedback
2. Hypothalamic-pituitary-target cell negative feedback system

Direct Negative Feedback:

The output shuts off the original stimulus

Direct Negative Feedback Example After Eating A Meal:

As levels of blood glucose increase (stimulus), the secretion of insulin increases, thus increasing movement of excess glucose into the cells and stored in the liver and skeletal muscle as glycogen (glycogenesis), as a result blood glucose levels decrease (shutting off the original stimulus). When glucose levels decrease, insulin secretion decreases.

Direct Negative Feedback Example Fasting:

1. Decreased blood glucose
2. Release of glucagon
3. Acts on liver cells to breakdown glycogen to glucose (glycogenolysis) and to synthesize new glucose from amino acids, glycerol, and lactic acid (gluconeogenesis).
4. Release of glucose by liver
5. Increased blood glucose levels
6. Decreased glucagon secretion

Direct Negative Feedback PIC:

What does the Hypothalamic-Pituitary-Target Cell Negative Feedback System regulate?

Regulates hormones of the thyroid, adrenal cortex, and gonads.

Hypothalamic-Pituitary-Target Cell Negative Feedback System Steps:

1. Hypothalamic-releasing hormones stimulate the release of tropic hormones from the anterior pituitary.
2. The tropic hormone then stimulates hormone release from the target endocrine gland to produce a response.
3. Rising blood levels of the hormone from the target endocrine gland (i.e. thyroid gland, adrenal gland, testes, ovaries) negatively feedback to the hypothalamus and anterior pituitary to shut off hormone release.

PIC: hypothalamic-pituitary-target organ (thyroid, adrenal, gonads)

Hypofunction of the hormone may be caused by:

Hyposecretion or receptor defects in the target organ.

Hyposecretion of Hormone - Reduced hormone secretion due to:

1. Congenital defects
2. Decline in function with aging
3. Atrophy of gland, surgical removal of gland
4. Destruction of endocrine gland (autoimmune, ischemia, infection)

Receptor Defects - The hormone is fine, but there is reduced receptor action due to:

1. Decrease in number of receptors - autoimmune destruction
2. Receptor insensitivity to the hormone - receptor does not respond as it should (i.e. in type II diabetes mellitus).

Hyperfunction of the hormone may be caused by:

1. Hypersecretion of the hormone
2. Exogenous administration of the hormone
3. Impaired excretion by the liver or kidney
4. A receptor defect
5. Autoantibodies that mimic hormone action

Hypersecretion of Hormone - Too much hormone secretion due to:

1. Hyperplasia of the Endocrine Gland
2. Benign Tumor
3. Paraneoplastic Syndrome

Hyperplasia of the Endocrine Gland EX:

In response to excessive TSH, the thyroid gland undergoes hyperplasia.

Benign Tumor:

Unregulated release (hypersecretion) of hormone that the tissue normally secretes and the tumor cells do not respond to negative feedback.

Benign Tumor.
EX:

EX: benign parathyroid tumor secretes excessive parathyroid hormone.

Paraneoplastic Syndrome:
EX:

When malignant tumor cells secrete a hormone that the tissue doesn't normally secrete.
EX: A small cell lung carcinoma secreting ACTH.

Exogenous Hormone Administration.
EX:

EX: Patients taking corticosteroid long-term may develop Cushing syndrome.

Impaired Excretion by Liver or Kidneys:

With liver or kidney failure, hormones may not be deactivated and excreted resulting in higher blood levels of the hormone.

How does liver failure contribute to hyperfuncton?

In liver failure ADH and aldosterone are increased contributing to ascites and edema due to impaired liver inactivation of these hormones.

Receptor Defect:

When the receptor responds excessively to the hormone.

Presence of autoantibodies against specific receptors which mimic hormone action.
EX Disease:

Graves Disease

Primary Endocrine Disorder:

Disorder originates in target gland responsible for producing the hormone.

Secondary Endocrine Disorder:

Target gland is normal, but function is altered by defective levels of stimulating hormones from the anterior pituitary.

Tertiary Endocrine Disorder:

Function of anterior pituitary and target gland are normal, but function is altered by defective levels of releasing hormones from the hypothalamus.

What are the basic diagnostic tests that are used in evaluating endocrine disorders?

1. Blood Tests
2. 24 hour urine sample
3. Stimulation test used when hypofunction is suspected
4. Suppression tests when hyperfunction is suspected
5. MRI
6. CT scan
7. Ultrasound

What do blood tests measure?

1. Check serum hormone levels
2. Test for autoantibodies

Stimulation test used when hypofunction is suspected.
EX:

Give ACTH and measure cortisol levels to see if cortisol increases (way to help differentiate primary and secondary disorders).

Suppression tests when hyperfunction is suspected.
EX:

Give glucose to see if GH is suppressed - for example, if it is not, suspect that GH release is not regulated (i.e. secreted by a tumor).

Primary Hypoparathyroidism:

Insufficient secretion of PTH as the result of deficient parathyroid glands, which results in low blood Ca2+ (hypocalcemia).

What causes Primary Hypoparathyroidism?

1. Congenital lack of the parathyroid glands.
2. Surgery to remove the thyroid glands resulting in accidental removal of the parathyroid glands.
3. Autoimmune disease
4. Radiation for thyroid cancer.

Secondary Hypoparathyroidism:
What is it caused by?

Decreased PTH secretion as the result of hypercalcemia due to the breakdown of bone with:
1. Immobility
2. Bone cancer.
PTH would be low as a result of high blood Ca2+.

Hypocalcemia Nervous System Mani:

1. Increased neuroexcitability of nerves leading to spontaneous contraction of skeletal muscle
2. Tingling in fingers and around mouth
3. Hyperactive reflexes

Hypocalcemia Skeletal Muscle Mani:

1. Muscle twitching and Spasms (tetany) first observed first in the face and hands.

Hypocalcemia Heart Mani:

1. Weak cardiac muscle contractions
2. Arrhythmias
3. Hypotension

Hypocalcemia Gastrointestinal Mani:

1. Increased Peristalsis
2. Diarrhea
3. Nausea
4. Cramps

How does hypocalcemia affect skeletal muscle?

Hypocalcemia does not weaken skeletal muscle contractions because sufficient calcium is stored in skeletal muscle cells.

How does hypocalcemia affect cardiac muscle cells?

Cardiac muscle cells, do not have large stores of calcium, but rely instead on calcium from the blood for contraction.

Primary Hyperparathyroidism Causes:

-Adenoma (Bening Tumor) of the parathyroid glands.
-Hyperplasia

When does Secondary Hyperparathyroidism occur?

Secondary to renal failure.

What does Secondary Hyperparathyroidism result in?

1. Decreased activation of vitamin D by the kidneys
2. Hyperphosphatemia
3. Hypocalcemia stimulates the parathyroid glands to release PTH (secondary hyperparathyroidism) which breaks down bone resulting in renal osteodystrophy.

Hyperphosphatemia effect:

Phosphate binds to calcium in the blood lowering free Ca2+ levels.

Hypercalcemia Nervous System Mani:

1. Decreased neuroexcitability
2. Apathy
3. Fatigue
4. Personality Change

Hypercalcemia Skeletal Muscle Mani:

-Muscle Weakness
-Decreased Tone

Hypercalcemia Heart Mani:

1. Forceful cardiac contractions
2. Arrhythmias
3. Tachycardia
4. Hypertension

Hypercalcemia Kidney Mani:

1. Polyuria
2. Thirst
3. Renal Insufficiency
4. Renal Calculi

Hypercalcemia Gastrointestinal Mani:

1. Decreased peristalsis
2. Constipation
3. Nausea

Hypercalcemia Bone Mani:

-Osteoporosis
-Spontaneous fractures

What gland is not a true endocrine gland?

The posterior pituitary.

Why is the posterior pituitary not a true endocrine gland?

The hypothalamus makes the hormones and transports them through the direct neural connection down axons to the posterior pituitary which stores them.

When does the posterior pituitary release hormones?

The posterior pituitary releases these hormones in response to depolarization of hypothalamic neurons.

What is the true endocrine gland?

The anterior pituitary is an endocrine gland that synthesizes and releases its own hormones

-What regulates the anterior pituitary?
-What does it do?

The hypothalamus which releases stimulating and inhibiting hormones that travel to the anterior pituitary by way of the hypophyseal portal system (direct vascular connection, by-passing the systemic circulation).

Hypopituitarism diagnosis:

Ranges from absence of one or more pituitary hormones to complete failure of all pituitary hormone function (panhypopituitarism).

What does hypopituitarism result in?

Leads to hypofunction of the secondary organs that depend on tropic stimuli from the pituitary.

Hypopituitarism.
EX Scenario:

EX: with low TSH from the pituitary gland, there will be less stimulation of the thyroid gland and hypothyroidism.

Hypopituitarism Etiology:

1. Congenital - you are born with it.
2. Infarction, infection, and head trauma to the pituitary/hypothalamus.
3. Pituitary tumors
4. Deficiency of hypothalamic hormones that stimulate release of pituitary hormones.

How can pituitary tumors result in hypopituitarism?

The tumor of one cell type can compress other cell types leading to hypersecretion of one hormone and hyposecretion of others.

Panhypopituitarism:

A deficiency of all pituitary hormones.

What does Panhypopituitarism result in?

1. cortisol deficiency - due to decreased ACTH secretion.
2. thyroid deficiency - due to decreased TSH secretion.
3. diabetes insipidus - due to decreased ADH secretion.
4. gonadal failure - due to decreased FSH and LH secretion.
5. loss of secondary sex characteristics - due to decreased LH secretion.
6, low growth in children - due to decreased GH secretion.
7. no lactation in postpartum women - due to decreased prolactin secretion.

What is the usual cause of Hyperpiuitarism?

Pituitary adenomas (benign, slow-growing tumors).

What do the benign tumors in hyperpiuitarism do?

These benign tumors secrete hormones of the cell type made up of the tumor resulting in hypersecretion of hormone.
As the tumor grows, it can compress other cell types resulting in hyposecretion of other hormones.

Manifestations you would see related to the mass and hormone secretion in hyperpituitarism:

Effect of mass as it enlarges and causes pressure in the skull (increased intracranial pressure) Manifestations: headaches, seizures, drowsiness, visual deficits.

GH's Growth promoting actions:

GH stimulates the liver to produce IGF-1, which acts on target tissues to increase protein synthesis and cell growth.