3. Endocrine physiology (Part 3).pptx

Thyroid Gland

• _{It is a butterfly-shaped with two lateral lobes, partially hidden} by sternocleidomastoid muscles, connected by isthmus just below cricoid cartilage.

Histology of the Gland

:

• _{The follicular lumen contains colloid.} This is a proteinaceous material and is primarily a store of thyroglobulin

secreted by the thyroid cells.

• _{The basic functional unit of the}

thyroid is the follicle (acini), a hollow sphere of cells surrounded by a

basement membrane.

• _{The cells are columnar and there will} be endocytic resorption of the

hormone-containing colloid.

• _{When the gland is inactive, the follicles are large and} the colloid is abundant, and the cells lining them are flat.

When the gland is active the follicles are small.

• _{The individual thyroid cells rest on a basal lamina that} separates them from the adjacent

• A few adjacent parafollicular cells called (c-cells) are larger and secrete calcitonin.

• The wall of the follicle is a single layer of thyroid cells. The follicular cells are cuboidal when inactive, and

Formation & Secretion of Thyroid Hormones

:

• The principal hormones secreted by the thyroid are thyroxine (T₄) and tri-iodothyronine (T₃). Approximately 87% of T₃ is produced by monodeiodination of T₄ in the periphery such as liver, muscle and kidney. Both hormones are

iodine containing amino acids.

• _{The functions of these two hormones are qualitatively the same, but they} differ in rapidity and intensity of action.

• _{T3 is more active & it is about four times as potent as T4, but it is present in} the blood in much smaller quantities and persists for a much shorter time than does T4.

Iodine Metabolism

• _{Iodine essential for thyroid hormone synthesis.}

• _{The major dietary sources are water, iodinated bread, iodinated salt,}

medications.

• _{Ingested iodine is converted to iodide and absorbed. The average}

dietary intake is approximately 500 μg/day.

• _{After its absorption of iodide from gastrointestinal tract it enters the}

inorganic iodide pool in the ECF. Iodide is actively concentrated in the thyroid gland, the salivary gland and the gastric gland, its role in salivary and gastric gland is not known.

Iodine Metabolism

• _{20% of this I}- _{enters the thyroid whereas 80% is excreted in the urine.}

Iodine is actively transported into the thyroid gland.

Thyroid Hormone Synthesis

:

•

_{Iodide is immediately oxidized to iodine (I}

0

_{) by}

hydrogen peroxide

and incorporated into tyrosine

molecule.

This is not free in solution but present in peptide linkage as components of thyroglobulin.

• _{Within the follicle thyroglobulin is iodinated to form both} monoiodotyrosine (MIT) and Diiodotyrosine (DIT). Later on two DIT molecules are coupled to form T₄ or one MIT and one DIT molecule are coupled to form T_3. These reactions

By this thyroid cells have three functions:

They collect and transport iodine.

They synthesize thyroglobulin and secrete it into the colloid.

Transport of TH: Protein binding

• _{Both T4 & T3 are bound to plasma protein.}

• _{Normally 0.02-0.2% is free and 99.8-99.98% is protein bound.}

• The half life of T4 is long (6-7 days). T₃ has a shorter half life than T₄ and its action on the tissue is much more rapid.

• _{The free thyroid hormone in plasma is physiologically active and it inhibits the} pituitary secretion of TSH.

• _{Some time fluctuation in binding proteins may occur particularly TBG:}

• _{Conditions which elevate TBG are: pregnancy, estrogen treated patients and} other drug treatments

• _{Conditions which depress TBG are: glucocorticoids and androgen treatment,} • _{but in both conditions the patients are neither hyperthyroid nor hypothyroid i.e.}

Regulation of Thyroid Secretion

:

• Thyroid function is regulated by variation in the circulatory level of pituitary TSH.

• TRH increase the biological activity of TSH.

• _{In patients with TRH deficiency, there is a drop in circulating TSH}

bioavailability.

• _{TSH has special receptors in the thyroid cell membrane.}

• _{When the pituitary is removed, thyroid function is depressed and the}

Control Mechanisms for TH secretion

:

Negative feed back

Endocrine Physiology

Mechanism of action of TH

• _{TH increase the transcription of large numbers of genes:} therefore, in virtually all cells of the body, great numbers of protein enzymes, structural proteins, transport proteins, and other substances are synthesized. The net result is generalized increase in functional activity throughout the body.

•

_{Thyroid Hormones Increase Active Transport of Ions Through}

Cell Membranes

•

_{TH activates nuclear receptors}

_{form hundreds of new}

intracellular proteins.

Endocrine Physiology

Thyroid Hormone Action:

1. Calorigenic action:

T₄ & T₃ increase the O2 consumption of almost all metabolically active tissues (except brain & some others). if

food intake is not increased so endogenous protein & fat stores are catabolized and weight is lost.

(it cause a rise in body temperature).

2.Effects of Nervous System

: thyroid hormone has marked effect on brain development. In hypothyroid infants synapses develop abnormally, myelination is defective and mental

3.Effects on Skeletal Muscles:

Muscle weakness occurs in most patients with hyperthyroidism.

4.Effects on the Heart:

thyroid hormones have marked chronotropic and ionotropic effects on the heart. In

hypothyroidism there are low C.O & decrease in HR while in

hyperthyroidism there is increased C.O & HR, with wide pulse pressure.

5.Relation to Catecholamines:

the action of thyroid hormones and catecholamines are interrelated. The cardiovascular effects, tremor and increased sweating produced by increased thyroid hormones such as in

6.Effects on Carbohydrate and Cholesterol Metabolism:

Thyroid hormones increase the rate of absorption of carbohydrates

from the GIT and also lower circulatory cholesterol level and these are independent of their calorigenic actions.

Conversely, decreased thyroid secretion greatly increases the plasma concentrations of cholesterol, phospholipids, and triglycerides and almost always causes excessive deposition of fat in the liver

7.Effects on Growth and Development:

Thyroid Hormones are

8.Effects on Endocrine System:

Thyroid hormone are

necessary for normal LH and FSH function, they are essential for normal menstrual cycle and fertility.

Increased TH increases the rates of secretion of most other endocrine glands, but it also increases the need of the tissues for the hormones.

9

.

Increased respiration

:

Activate all mechanisms that increase the rate and depth of respiration

.

10. Increased GI motility

: increase both the rate of secretion

• _{when the dietary iodine intake decreased TH synthesis and}

secretion decline so TSH secretion increases,

• _{the thyroid hypertrophy producing an iodine deficient goiter}

that may become very large. (In areas where iodine has been leached out of the soil by rainwater so that food grown in the soil is

Cretinism:

• _{children who are}

_hypothyroid

from birth are called cretins.

• _{They are dwarfed and mentally}

retarded and have enlarged protruded tongue.

• _{If treatment is started soon after} birth, the stigmas of cretinism