PATHO2) W5 - Alterations of Hormonal Regulation Part 1

Functions of The Endocrine System

-Differentiation of reproductive system and CNS in fetus

-Stimulation of growth and development

-Coordination of the male and female reproductive systems

-Maintenance of internal environment

-Adaptation to emergency demands of body

Hormones

General characteristics: Specific rates and rhythms of secretion- Diurnal, pulsatile, and cyclic and patterns that depend on circulating substances

-Operate within feedback systems

-Affect only target cells with appropriate receptors

-Are excreted by kidneys or deactivated by liver or cellular mechanisms

Regulation of Hormonal Release

Hormones are released:

-In response to an alteration in the cellular environment

-To maintain a regulated level of certain substances or other hormones

- Hormones are regulated by chemical, endocrine, or neural factors

-Hormones are released into the circulatory system by endocrine glands and distributed throughout body

Positive Feedback

-Response to stimulus increases synthesis and secretion of hormone

-Thyrotropin-releasing hormone

Negative Feedback

•Response to stimulus decreases synthesis and secretion of hormone

•Thyroxine and triiodothyronine

Explain Feedback Loops Using the Charts

Okay.

Target Cells

-have Plasma membrane or intracellular hormone receptors. hormone binds -Initiate signal to intracellular effectors

Up-Regulation

Low concentrations of hormone = increase number or affinity of receptors

Down-regulation

High concentrations of hormone decrease number or affinity of receptors

Lipid-Soluble Hormones

-Steroid hormones

-Primarily circulating bound to a carrier

-Relatively small

-Rapid and long-lasting response

-Diffuse freely across the plasma and nuclear membranes

-Bind with cytosolic or nuclear receptors

Water- Soluble Hormones

-Protein hormones and catecholamines

-Circulate in free, unbound forms

-High molecular weight

-Short-acting response

-Cannot diffuse across plasma membrane)

-Bind to surface receptors

• Initiate first and second messengers

Mechanisms of Hormonal Alterations

Significantly altered hormone levels due to:

-Inappropriate amounts of hormone delivered to target cell

• Disorders of endocrine glands

• Failure of feedback systems

• Dysfunctional hormones

• Defects in hormone delivery

  -Inappropriate responses by the target cell

  • Abnormalities in receptors

  • Intracellular disorders

Hypothalamic-Pituitary System (HPA)

-Structural and functional basis for integration of neurologic and endocrine systems (Neuroendocrine system)

-Hypothalamus

-Pituitary gland = Anterior pituitary + Posterior pituitary

Anterior Pituitary Gland

Hormones regulated by :

-Secretion of hypothalamic releasing factors

-Feedback effects of hormones

-Direct effects of mediating neurotransmitters

ex. MSH, FSH, ACTH

Posterior Pituitary Gland

Hormones:

Antidiuretic hormone (ADH)

Think back to Diabetes Insipidus and SIADH (Controls plasma osmolality)

Oxytocin: Uterine contractions, milk ejection in lactating females Sperm motility in males

Alterations of the Hypothalamic-Pituitary System

A. Causes of interruption:

-Destructive lesions Rupture after head injury

-Surgical transection

-Tumor

B. Loss of hypothalamic hormones causes pituitary to release inadequate amounts of hormones

Hypopituitarism (diseases of the anterior pituitary)

-Hypopituitarism = Absence or failure of anterior pituitary hormones

-Panhypopituitarism—all hormones deficient

-Caused by: Pituitary infarction Space-occupying lesions, Traumatic brain injury, Removal of destruction of gland, Infections, Autoimmune hypophysitis

-Symptoms related to cortisol insufficiency

Hyperpituitarism (diseases of the anterior pituitary)

Hypersecretion of hormones:

Commonly caused by a benign, slow-growing pituitary adenoma

Manifestations related to tumor growth and hormone hyper/hyposecretion

Hypersecretion of GH

Acromegaly & Giantism

Acromegaly

Hypersecretion of GH during adulthood

Slow and progressive, may lead to heart disease and insulin resistance

Symptoms: Connective tissue proliferation, hyperglycemia, enlarged tongue, course skin/hair, enlargement of bones in face, hands, & feet

Giantism

Hypersecretion of GH in children whose epiphyseal plates have not yet closed

Results in excessive skeletal growth

Prolactinoma

Hypersecretion of prolactin

-Prolactin heavily affects reproductive organs and Elevations suppresses FSH and LH

-Causes Estrogen/Progesterone deficiency in women & Testosterone deficiency in men

Manifestations of Prolactinoma

In females: amenorrhea, galactorrhea, hirsutism, and osteopenia

In males: gynecomastia, hypogonadism, and erectile dysfunction

Thyroid Gland

Thyroid hormone (TH)

Secreted in response to Thyroid Stimulating Hormone (TSH)

90% T4 and 10% T3 -Most T4 then converted to T3

Actions: Growth, maturation and functions of cells and tissues

Genetic expression of proteins

Function of blood cells and muscle tissue Cell metabolism, heat production, and oxygen consumption

Primary vs. Secondary Thyroid Disorders

Primary thyroid disorders Dysfunction or disease of thyroid Increased or decreased thyroid hormone (TH) Idiopathic, caused by autoimmune mechanisms

Central (secondary) thyroid disorders Disorders of pituitary gland thyroid stimulating hormone (TSH) production

Hyperthyroid conditions

Graves disease (80% of Hyperthyroid cases)

-Autoimmune disease caused by stimulation of thyroid by autoantibodies against TSH receptor

-Type 2 Hypersensitivity

Hyperthyroidism resulting from nodular thyroid disease

-Toxic multinodular goiter

-Toxic adenoma

Thyrotoxic crisis (thyroid storm)

-TH levels rise dramatically, can be fatal

Exopthalmos & Pretibial Myxedema

big bulging eyes & thickened swollen skin on shins

grave’s disease, hyperthyroidism

Thyrotoxicosis

Rare but dangerous condition due to any cause of increased TH levels, Death can occur in 48 hours

-Can be triggered by stress, infection, trauma, seizures, or surgery.

Manifestations: Tachycardia, hyperthermia, HF, N/V, diarrhea,

Hypothyroidism

Deficient production of TH by thyroid gland

a. Primary: Loss of thyroid function

Caused by autoimmune thyroiditis, loss of thyroid tissue, medications, and endemic iodine deficiency

b. Central (secondary) Failure of pituitary to synthesize adequate TSH

Caused by pituitary tumors and associated treatments

Manifestations are decreased metabolic rate, cold intolerance, and lethargy

Hypothyroid conditions

1. Hashimoto disease = Autoimmune disease-causing gradual destruction of thyroid tissue

2. Congenital hypothyroidism = Thyroid tissue absent, Hereditary defects in TH synthesis

3. Subacute thyroiditis (de Quervain thyroiditis) = Nonbacterial inflammation of thyroid, often follows a virus; usually resolves in 3-4 months

4. Postpartum thyroiditis = Occurs up to 6 months after birth, course similar to Subacute thyroiditis

Thyroid Carcinoma

-Most common endocrine malignancy

-Ionizing radiation most common cause

-Typically presents as small thyroid nodule (May metastasize to lung, brain, or bones)

-May cause changes in voice, swallowing, or difficulty breathing depending on size/location -Diagnosed with fine needle aspiration

-Treated with thyroidectomy, suppression therapy, radiation, and chemotherapy

Parathyroid Glands

a. Small glands located behind the upper and lower poles of the thyroid gland

b. Produce parathyroid hormone (PTH)

-Increases serum calcium and decreases serum phosphate

-Promotes calcium and phosphate absorption to enhance bone mineralization

-Vitamin D (cofactor) needed for PTH function

Hyperparathyroidism

-Increased secretion of parathyroid hormone (PTH)

Classified as…

1. Primary— excess secretion of PTH from one or more parathyroid glands

-Normal feedback loop impaired

2. Secondary—Compensatory increase in PTH secondary to chronic hypocalcemia

-Despite hypersecretion, normal Calcium levels not achieved d/t low Vitamin D

3. Tertiary—develops after long period of hypocalcemia

-Hallmark manifestations are hypercalcemia and hypophosphatemia

Hypoparathyrodism

Abnormally low PTH levels Usually caused by parathyroid damage in thyroid surgery Manifestations are primarily those of hypocalcemia

Normal Calcium Levels

8.8-10.5 MG/DL

Hypocalcemia

Increased excitability

Muscle Spasms

Intestinal cramping & hyperactive Bowel Sounds

Tetany

Cardiac arrest

Hypercalcemia

Fatigue ,Constipation, Kidney Stones , Bradycardia, Cardiac Arrest, Bone Pain