Lecture 2 Dr. Rand Abdulateef

Lecture 2 Dr. Rand Abdulateef

THYROID GLAND

In healthy adults, the thyroid lies anterior to the larynx and has two lobes connected by an isthmus. Each lateral lobe is about 5cm. long, 3-4cm. wide, 2-3cm. deep, and weighs 15-20g.

Embryologically the thyroid develops from a downgrowth of endoderm, it varies in size and structure in response to many factors among which are sex, age, nutrition ,temperature, season & iodine content.

The thyroid is enclosed by a thin collagenous capsule from which internal septa penetrate the parenchyma, dividing it into irregular lobules.

The glandular component of the thyroid is composed of tightly-packed spherical structural units of varying size called thyroid follicles.

·  Thyroid follicles:

Each lobule consists of numerous spherical follicles (about 30 million follicles in human).Each follicle is lined by a single layer of specialized thyroid epithelium which rests on a basement membrane and encloses a lumen filled with thyroid colloid which is an eosinophilic, homogenous proteinaceous material rich in thyroglobulin.

The follicles are surrounded by basal lamina and reticular fiberswith a network of blood vessels, including fenestrated capillaries, unmyelinated nerve fibers are present in the walls of the thyroid arteries, most of these terminate in plexuses around the blood vessel.

The follicles, vary in size and appearance according to the region of the gland and its functional activity.

v  Thyroid Follicular Cells:

·  Structure:

·  Using light microscopy shows that thyroid follicular cells varies in shape from squamous in inactive glands to columnar during stimulation, intercellular boundaries are distinct.

·  They have rounded nuclei with basophilic cytoplasm contains lipid droplets.

·  With electron microscope, the apices of the cells show microrvilli that lengthen with increased activity of the cells with well developed RER & Golgi which are necessary for the production and secretion of protein material.

·  Stimulation by pituitary TSH increases synthesis and secretion.During an active secretory phase the thyroid follicular cells show:

•  more prominent endoplasmic reticulum &free ribosomes.

•  Golgi enlarges.

•  surface microvilli increase in number and length.

•  intracytoplasmic droplets appear.

·  Thyroid follicular cells secrete glycoprotein molecules called thyroglobulin, iodine molecules and enzymes into the cavity of the follicle.

v  Steps of the formation of T3, T4:

a) Synthesis and storage of thyroglobulin.

1.  The amino acids are absorbed from the blood stream & formed into poly-peptides in the RER,

2.  The carbohydrate mannose is added to the molecule within the RER,

3.  When the molecule arrives at Golgi apparatus galactose is added and the thyroglobulin molecule is formed.

4.  The thyroglobulin molecules are now packaged into vesicles that are discharged from the luminal surface of the cell by exocytosis.

b) Uptake and oxidation of iodide.

1.  Iodide is absorbed from the blood and is oxidized to iodine by the enzyme peroxidase within the follicular cells.

2.  The iodine molecules are then concentrated within the cells and finally passed out into the cavity of the follicle.

c) Iodination of thyroglobulin and formation of thyroid hormone

Once the thyroglobulin and iodine reach the follicular cavity, formation of the two hormones tetraiodothyronine(thyroxine;T4) and triiodothyronine(T3) starts and stored in the thyroglobulin colloid in the cavity of the follicle and may remain there for as long as 3 months . (T3 &T4 are iodinated derivatives of Tyrosine).

Although T4 makes up 90% of the thyroid hormone produced, it is less potent than T3.

d) Thyroid hormone secretion.

Stimulation by TSH causes the follicular cells to pinocytose portions of the colloid, forming vesicles containing iodinated thyroglobulin. These vesicles fuse with lysosomes carrying enzymes that split the thyroglobulin. The T4 and T3 released in this way diffuse out of the secondary lysosomes, pass through the cytoplasm and cross the basolateral plasma membrane to reach the bloodstream (a process called endocytosis).

e) Targets and effects of thyroid hormones.

T3 and T4 act throughout the body to increase basal metabolic rate (ie, the rate at which cells use glucose), promote cell growth, increase heart rate, raise body temperature, and generally enhance all energy- requiring cell functions. They also act on the TRH-secreting cells of the hypothalamus and the thyrotropes in the adenohypophysis to reduce TSH secretion .

v  Parafollicular Cells (C Cells):

These cells have the following characteristics:

·  oval in shape, larger than the follicular cells.

·  present singly among the follicular cells lying within the follicular basement membrane or in clusters in between the follicles.

·  They have poorly stained cytoplasm which typically appears clear or white.

·  Electron micrographs reveal numerous small secretory granules which secrete a peptide hormone calcitonin in response to high blood calcium.Calcitonin increases calcium deposition in the bone lowering blood calcium (an effect opposite that of the parathyroid hormone).

·  Parafollicular cells are not under the control of pituitary gland but are stimulated by hypercalcemia and suppressed by hypocalcemia.

·  Hyperthyroidism (thyrotoxicosis, Graves disease) is most common in middle-aged women, the thyroid gland is diffusely enlarged. multinodular goiter occure in elderly.

·  Hypothyroidism occurs in two forms, cretinism in infants & children and myxedema in adults.

·  Simple goiter Enlargement of thyroid gland not associated with hyper or hypothyroidism, thyroiditis or tumor, iodine deficiency is the most common cause, and the condition occurs more frequently in women.

PARATHYROID GLANDS

·  Parathyroid glands are four (in some people up to eight), small, ovoid, yellowish brown structures related to the posterior border of the thyroid gland one at each of the upper and lower poles in the capsule of the thyroid, they could be found embedded in the thyroid tissue or beside the thymus because both originate from 3ed and 4th pharyngeal pouches

·  The normal parathyriod is surrounded by a thin fibrous capsule from which a delicate septa carrying the blood vessels and pass into the gland between the clusters of secreting cells among which lie sinusoidal capillaries.

·  The parenchyma of the parathyroid glands in adults contains 3 types of cells:

Adipocytes, 2 .Chief cells, 3. Oxyphil cells.

1. Adipocytes :

§  appear in the parenchyma at puberty and gradually increase in number until age of 40 years then remain constant proportion of the entire gland then decrease in old age.

§  they form a background stroma in which the chief and oxyphil cells are arranged close to a fine network of capillary vessels.

2. Chief Cells (parathormone cells):

These are the active component of the parenchymal cells.

v  Structure.

·  small spherical cells (4-8µm in diameter).

·  the most numerous cells.

·  have central, dark staining nucleus.

·  slightly acidophilic cytoplasm, some chief cells cytoplasm looks light colored because of the presence of large amount of glycogen, in other the cytoplasm is darker due to very little glycogen.

·  Ultrastructurally, they contain a well developed Golgi apparatus, mitochondria, rough endoplasmic reticulum (RER) and numerous small secretory granules.

·  Chief cells secrete parathyroid hormone (PTH) in response to low blood calcium. PTH increases blood calcium by acting at three target sites :

•  bone PTH increases bone resorption .

•  kidneys it increases phosphate excretion and calcium reabsorption and causes activation of a vitamin D precursor.

•  intestines PTH causes increased absorption of calcium by the intestinal mucosa.

3.Oxyphil Cells:

•  begin to appear at about age 7 and increase in number with age.

•  are less numerous and larger than chief cells (about 10 µm in diameter)

•  polygonal in shape, have small spherical and dark-staining nuclei.

•  their cytoplasm contains many acidophilic granules.

•  ultrastructurally, oxyphil cell cytoplasm is packed with large active mitochondria, with scanty free ribosomes and glycogen.

•  endoplasmic reticulum and neurosecretory vacuoles are uncommon, indicating that the cells are NOT endocrinologically active.

•  transitional cell forms with features of both oxyphil and active chief cells are occasionally seen.

•  Oxyphil cell function is not clearly understood.

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