thyroid adv human phys

thyroid hormone

stimulates thyroid gland to release T3, T4, and calcitonin (and C cell)

T4 becomes T3 in tissues

secretions must be absorbed back through the epithelium to enter the blood stream

thyroid gland

composed of follicles lined with cuboidal epithelial cells that secrete colloid inside

negative feedback inhibition

colloid

mainly thyroglobulin (tyrosine AA), which contains the thyroid hormones

iodine

needed to make T4 and T3; transported in with sodium (____ trapping)

pendrin (counter transport molecule) transports ___ inside the follicle

oxidized form of iodide (by thyroid peroxidase); couples w/ Thyroglobulin

thyroglobulin

secreted from ER and Golgi into follicle; made of tyrosine

is cleaved to T3 and T4 and secreted; stored for months inside follicle

TSH

secreted from anterior pituitary, increases T4 & T3 by:

increasing cleavage of TG, activity of iodine pump, iodination, # of cells, and cell size and secretory activity

thyroid hormone transport

bound to plasma proteins in the blood - released slowly into target cells; used slowly by target cells.

‘Revs up’ the system – increases functional activity in the body

thyroid hormone effects

• Bone growth and development

• Increases cardiac output (CO) and lipolysis

• Cholesterol metabolism in the liver

• Myelination in the brain of axonal growth of neurons

• Stimulates Growth Hormone, inhibits TSH (negative feedback)

thyroid diseases

• Alterations in circulating levels of thyroid hormone

• Impaired metabolism of thyroid hormone in periphery

• Resistance to thyroid hormone at level of tissues

• Hypothyroidism, hyperthyroidism, goiter

hypothyroidism

• mostly disease of thyroid gland. 

  • Associated with low metabolic state; low hormone levels; enlarged thyroid

  • (Hashimoto disease; autoimmune); destroys thyroid gland

  • Goiter (too little iodine)

  • Diagnostics – similar to hyperthyroidism, treat with Thyroid hormone

hypothyroidism signs/symptoms

weight gain, slow HR/CO, fatigue and sleeping 12-14 hours/day, mental sluggishness

• Myxedema – swelling of eyes /face; bag under eyes

• Atherosclerosis – lack of thyroid hormone increases cholesterol

hyperthyroidism

excessive thyroid function.

Increased basal metabolic rate, cardiac and autonomic nervous system dysfunction.

Most common is Graves Disease

hyperthyroidism signs/symptoms

Sweating, exophthalmos, goiter, arrythmia/tachycardia, nausea/diarrhea, oligomenorrhea (in females), tremor, muscle weakness

Headache, weight loss, nervousness, emotional instability

goiter causes

little iodine, hypothyroidism, hyperthyroidism, tumors, autoimmune

parathyroid glands functions

• Bone resorption and Ca2+ into circulation

• Ca2+ reabsorption in the kidney and phosphate excretion

• Activation of Vitamin D (calcitriol); aids of resorption of calcium in kidneys

blood calcium levels

• HIGH calcium levels in blood stimulate CALCITONIN release from THYROID

• LOW calcium levels in blood stimulate PTH release from PARATHYROID

blood calcium importance

most of calcium is in the BONE (99%); very small amount of calcium in blood

precisely controlled

calcium is important in muscle contraction (skeletal, smooth, cardiac), neural transmission, bone

calcemia

HYPERcalcemia = cause depression of the nervous system

HYPOcalcemia = tetany

calcitonin

produced during HIGH blood calcium levels

increased excretion of calcium in kidneys

calcium deposition in bone (osteoclast inhibition)

blood calcium levels decline

parathyroid hormone (PTH)

produced during LOW blood calcium levels

release of stored calcium form bone (osteoclast stimulation)

enhanced reabsorption of calcium in kidneys

stimulation of calcitriol production (kidneys); enhanced Ca2+, (PO4)^3- absorption by digestive tract

blood calcium levels increase

normal calcium levels

8.5-11 mg/dl

high calcium sensing pathway

G-protein coupled receptor → phospholipase → AA → leukotrienes → inhibit PTH release and cause degradation

low calcium sensing pathway

GPCR relaxes to allow PTH release

biphasic response: PTH that had been pre-formed can be released rapidly in response to acute changes in Ca2+

sustained low calcium then causes increased PTH synthesis

phosphate

increases PTH by inhibiting phospholipase/AA formation (removes the inhibitory effect)

patients with renal disease (elevated _____) = hyperparathyroidism + bone loss

alkaline _____ in blood = early marker of bone turnover

PTH pathway image

PTH and bone

when blood calcium falls, PTH is released and helps cause bone resorption

osteoblasts express rank ligand/RANKL (reverse receptor)

preosteoclasts bind to RANKL and bind together = osteoclast maturation

mature osteoclast secretes acid to breakdown bone so calcium can be resorbed

OPG

acts as decoy; helps osteoblasts lay down bone

binds to RANKL receptor on osteoclast to prevent maturation and bone resorption

stimulated by estrogen; menopause decreases estrogen and ____

kidney functions

Ca2+ reabsorption; increases channels in cell membrane to allow calcium to be drawn back in

phosphate excretion (reduced expression of Na+/(PO4)^2- cotransporter)

activation of enzyme 1alpha-hydroxylase to form active Vitamin D

calbindins pick up calcium and bring it to other side of cell

chronic renal failure

phosphates not excreted build up and stimulate PTH; can lead to bone loss

kidney cell image

vitamin D

stimulates calbindin and calcium ATPase pump

important with calcium absorption in GUT + deposition and resorption of bone

receptors located on nuclei – stimulate transcription

PTH and vitamin D

PTH makes active form of vitamin D by stimulating 1-alpha hydroxylase to form calcitriol

PTH causes conversion in the proximal tubules of kidneys of 25-hydroxycholecalciferol to 1,25-dihyroxycholecalciferol (active Vitamin D; calcitriol)

hyperparathyroidism

usually from adenoma; overproduction of PTH; can also be from kidney disease

treatment: if adenoma = surgery for removal or medications

• “Hungry Bones”: following surgery, shift in bone metabolism from chronic resorption to net bone formation = causing hypocalcemia

hyperparathyroidism signs/symptoms

high blood calcium, bone loss/pain/fracture, increased urination, kidney stones, muscle weakness, twitches, heart palpitations

hypoparathyroidism

results in low calcium, high phosphorus; less common