Transcript 2. Thyroid Gland T 4 and T 3

2. Thyroid Gland
• located anteriorly in cervical region, just inferior to thyroid
cartilage; two lobes connected by thin isthmus
• largest purely endocrine gland in body
• consists of follicles (cuboidal or simple squamous
epithelium) filled with colloid (combination of protein
[thyroglobulin] containing amino acid tyrosine [building
block of thyroid hormones])
• parafollicular cells produce calcitonin
http://www.usc.edu/hsc/dental/ghisto/end/c_26.html
2. Thyroid Gland: T4 and T3
• hormones based on amino acid tyrosine (differ in number
of iodine ions)
– thyroxine (tetraiodothyronine [T4]) and
– triiodothyronine (T3)
• T3 is 10x more active, but less common (T4 accounts for
about 90% of all thyroid hormone)
• much T4 converted to T3 by liver, kidneys, some other
tissues
2. Thyroid Gland: T4 and T3
• affect metabolic rate of every cell in the body, except brain,
spleen, testes, uterus and thyroid gland
– affect other activities within these organs and glands
• readily cross membranes (diffuse through plasma
membrane to bind to mitochondrial receptors and
receptors in nucleus)
2. Thyroid Gland
T4 and T3: Actions
• increase synthesis of enzymes involved in cellular
respiration --> increase basal metabolic rate
– increases glucose oxidation --> ATP synthesis
• increases ATP synthesis in cytoplasm and by
mitochondria
– results in increased heat production (calorigenic effect)
• work with GH to promote normal tissue growth and
development, especially important to
growth/development of CNS, skeletal and reproductive
systems
T4 and T3: Control
• release stimulated by TSH (thyroid-stimulating hormone
from adenohypophysis)
– release of TSH stimulated by TRH from hypothalamus
• release of TRH is stimulated by cold, pregnancy, low
thyroxine
• release inhibited by GHIH, high glucocorticoid levels, high
sex hormone levels, high iodine
Hypothyroidism
• too little thyroid hormone (thyroid gland defect, inadequate TSH, TRH,
or iodine)
– Hashimoto’s thyroid – autoimmune disorder in which thyroid is
attacked and function decreases
– myxedema - low BMR, constipation, puffy eyes, edema, lethargy,
mental sluggishness
– endemic goiter - enlargement of thyroid gland usually due to lack
of sufficient iodine
– cretinism - genetic deficiency of thyroid gland or lack of dietary
iodine during development resulting in mental retardation,
disproportionate growth, short body with thick tongue and neck
• treatment - reversed by iodine supplements or hormone replacement
therapy
Goiter
swelling in neck due to thyroid hypertrophy
both hypo- and hyperthyroidism
Hyperthyroidism
• too much thyroid hormone (thyrotoxicosis)
– Grave’s disease - autoimmune disease in which abnormal
antibodies similar to TSH mimic its function and
continuously stimulate release of thyroid hormones;
results in high BMR, sweating, rapid heart rate, weight
loss, restlessness, mood shifts, fatigues easily, limited
energy; also toxic goiter
– exophthalmos - protrusion of eyeballs, fibrous tissue
become edematous (swollen)
• treatments - removal of thyroid gland or irradiation
– patient must be on synthetic thyroid hormone the rest of
his/her life
2. Thyroid Gland: Calcitonin (CT)
• polypeptide produced by parafollicular cells
• actions: decreases blood calcium levels by:
– stimulating osteoblasts (Ca2+ uptake and incorporation
into bone)
– inhibiting osteoclast activities (osteoclasts break down
bone matrix releasing calcium)
• control: responds directly to blood calcium levels
• very rapid effect
• probably more important during childhood when it
stimulates bone growth
• important because at high blood Ca2+, membranes become
less permeable to Na+
3. Parathyroid Glands
• 2 paired structures on posterior of thyroid gland
• oxyphyil cells - function unknown
• chief cells secrete parathyroid hormone (PTH; protein)
• actions: increases blood Ca2+ by:
– stimulating osteoclast activity (which break down bone
matrix) while inhibiting osteoblasts (which form bone
matrix)
– stimulating increased reabsorption of Ca2+ by kidney
– indirectly stimulating increased absorption of Ca2+ by
small intestine by causing secretion of calcitrol form
kidneys
3. Parathyroid Glands
http://www.usc.edu/hsc/de
ntal/ghisto/end/c_32.html
Hyperparathyroidism
• rare; caused by parathyroid gland tumor
• results in hypercalcemia (excess Ca2+ levels in blood) -->
depression of nervous system (because of effect on sodium
permeability), abnormal reflexes, skeletal muscle weakness,
nausea, vomiting, kidney stones, calcium deposits in soft
tissues; bones become soft
Hypoparathyroidism
• trauma to or removal of parathyroid gland
• results in hypocalcemia (low blood Ca2+) --> neurons become
too excitable --> muscle tetany --> spasms/cramps -->
respiratory paralysis --> death
4. Adrenal Glands
• located in abdominal cavity against back wall
(retroperitoneal), superior to kidney
• surrounded by connective tissue capsule
• two regions:
– cortex - outer region, “glandular”, three zones
• zona glomerulosa - outer zone
• zona fasciculata - middle zone
• zona reticularis - inner zone
– medulla - inner region, modified
neural tissue (develops from same
tissue in embryo as ganglionic
[postganglionic] neurons of
sympathetic division)
4. Adrenal Gland: Regions and Zones
Adrenal Cortex: Zona Glomerulosa
• produces steroid hormones based on cholesterol
• mineralocorticoids - ion (and water) balance
– main hormone is aldosterone
• action:
* stimulates reabsorption of Na+ and secretion of K+ from
kidney, sweat glands, salivary glands, pancreas
– secondarily, increases water reabsorption in kidney (water
follows Na+)
Adrenal Cortex: Zona Glomerulosa
control:
• aldosterone release stimulated by:
– high K+, low Na+
– angiotensin II (result of renin-angiotensin pathway
stimulated by low blood pressure),
– ACTH (when under severe stress)
• inhibited by low K+, high Na+
Adrenal Cortex: Zona Glomerulosa
Disorders:
• aldosteronism = hypersecretion (adrenal
tumor)
→ increased water and Na+ reabsorption -->
hypertension, edema;
→ loss of K+ --> disruption of neural and muscle
function
Adrenal Cortex: Zona Glomerulosa
Disorders:
• Addison’s Disease = hyposecretion glucocorticoids and
mineralocorticoids
– results in decreased Na+ and water reabsorption,
increased blood K+ --> low blood volume -->
hypotension, dehydration;
– changes in membrane potentials --> disruption in
neural and muscular function
– also decreased cortisol secretion by zona fasciculata -->
decreased blood glucose levels (especially during
prolonged stress)
Adrenal Cortex: Zona Fasciculata
• glucocorticoids - effects on glucose metabolism
• main hormone is cortisol (hydrocortisone)
• actions:
– maintains blood glucose levels, especially in times of stress,
by:
• promoting gluconeogenesis (making new glucose in
liver) and use of alternative fuels by other cells (saves
glucose for the brain)
– anti-inflammatory decrease immune response
* can be used clinically to treat allergic reactions (e.g., poison
ivy), rheumatoid arthritis
Adrenal Cortex: Zona Fasciculata
• Control
– stimulated by ACTH
– inhibited by cortisol (inhibits secretion of CRH
from hypothalamus)
– blood levels peak in the morning
Disorders:
• Addison’s Disease
- hyposecretion of glucocorticoids and
mineralocorticoids
Zona Fasciculata: Cushing’s Disease
• hypersecretion of glucocorticoids
• caused by hypersecretion of ACTH due to tumor in ZF,
pituitary, lungs, kidneys, or pancreas
• suppresses glucose metabolism resulting in
– hyperglycemia (elevated glucose= steroid diabetes),
– stimulates lipid metabolism (weight loss),
– loss of muscle and bone mass,
– “buffalo neck” and “moon face” (fat redistribution),
– anti-inflammatory effects (mask infection)
– water and salt retention (effect of aldosterone
hypersecretion --> water retention --> hypertension)
Adrenal Cortex: Zona Reticularis
• gonadocorticoids
• most are androgens (“male” sex hormones) converted to testosterone; small amounts of
estrogens
• actions: may contribute to onset of puberty
(levels rise between 7 and 13 years of age; exact
function compared to hormones from ovaries or
testes unclear)
• control: stimulated by ACTH
Adrenal Cortex: Zona Reticularis
• hypersecretion results in:
– masculinization and masculine pattern of hair
distribution in females
– in males - rapid maturation of reproductive
organs, secondary sex characteristics;
hypersecretion of estrogens causes feminization
and gynecomastia (enlarged breasts)
Adrenal Medulla
• chromaffin cells (modified neurons - arise from
same embryonic tissue as postganglionic
neurons of sympathetic division)
• catecholamines - epinephrine (~80%), norepi
(NE)
• control: secretion stimulated by preganglionic
fibers of sympathetic nerves during flight-orfight response
Adrenal Medulla
• actions:
– epinephrine (more potent) - increases HR (beta
receptors), bronchodilation (in lungs), increased
blood glucose (breakdown of glycogen in liver
and skeletal muscle, and breakdown of adipose
tissue)
– NE - peripheral vasoconstriction --> increased BP