Intro To The Function Of Thyroid Gland 4j344v

Physiology of The Thyroid Gland

M. Djauhari Widjajakusumah Department of Physiology Fakultas Kedokteran Universitas Indonesia

THE THYROID GLAND 

One of the largest endocrine gland



Consists of two lobes lie on either side of the trachea



Highest blood flow rates of any tissue in the body



Tremendous capacity for growth: appropriate stimulus greatly enlarged (goiter/struma)

Figure 18–1. Ganong’s Review of Med Physiol 22th ed, 2006

THE THYROID GLAND

 

Made up of multiple acini (follicles) Each spherical follicle •

•

is surrounded by a single layer of cells is filled with protein-containing material: colloid, which major component is thyro-globulin that serves as the precursor of thyroid hormones.

Ganong’s Review of Med Physiol 22th ed, 2006

Ganong’s Review of Med Physiol 22th ed,

THE THYROID GLAND’S FOLLICLES 

Inactive gland:  the colloid is abundant  the follicles are large  the lining cells are flat



Active gland:  the edge of the colloid is scalloped: forming “reabsorption lacunae”  follicles are small  lining cells are cuboid or columnar Ganong’s Review of Med Physiol 22th ed, 2006

THE MAIN FUNCTIONS OF THYROID HORMONES 

Maintain the level of metabolism in the tissues for their normal function



Stimulate the O2 consumption of most cells in the body



Help regulate lipid and carbohydrate metabolism



Necessary for normal growth and maturation

FROM IODIDE TO THYROID CIRCULATING HORMONES 

Trapping



Iodide Hormone Synthesis:  oxidation  iodination  coupling reaction (oxidative condensation)



Hormone Secretion

Outline of thyroid hormone biosynthesis. Iodination of tyrosine takes place at the apical border of the thyroid cells while the molecules are bound in peptide linkage in thyroglobulin.

Plasma

I-

I-

Thyroid cell

Active transport

Thyro-globulin molecule

Colloid Oxidation (Thyroid peroxidase) II Iodide Iodine

I-

Monoiodotyrosine (MIT) Diiodotyrosine (DIT)

I

MIT +DIT DIT +MIT

Tyrosine

Alanine+ Alanine+

DIT +DIT

Triiodothyronine (T3) Reverse Triiodothyronine (RT3) Alanine+

Thyroxine (T4)

IODIDE TRAPPING 

Iodide active transport from circulation to the colloid



Stimulated by Thyroid Stimulating Hormone (TSH)



Iodide is pumped into the cells against the electrical gradient (resting membrane potential 50 mv) “iodide pump” (competitively inhibited by perchlorate and other anions)



Iodide then diffuses down the electrical gradient into the colloid

HORMONE SYNTHESIS 

Oxidation (thyroid peroxidase):  Iodide is oxidized to iodine



Iodination (thyroid peroxidase; blocked by propylthiouracil)  binding of iodine to thyrosine-thyroglobulin Mono-iodotyrosine (MIT)  binding of iodine to MIT Di-iodotyrosine (DIT)



Coupling reaction / oxidative condensation (thyroid peroxidase)) 

MIT + DIT

Tri-iodothyronine (T3)



DIT + DIT (T4)

Tetra-iodothyronine/Thyroxine

HORMONE SECRETION

(1) Colloid (with all its contents) ingestion / endocytosis reabsorption lacunae (2) Endocytotic vacuoles of colloid merge with lysosome (protease):  peptide bonds between iodinated tyrosine and thyroglobulin are broken free T4, free T3, free DIT and free MIT are liberated

HORMONE SECRETION

(3) Iodinated tyrosine (DIT, MIT) are deiodinated by iodotyrosine deiodinase free iodine and tyrosine-thyroglobulin compounds are liberated, and are reutilized. (4) Free T3 and free T4 into the circulation

Secretion and interconversion of thyroid hormones in normal adult humans. Figures are in micrograms per day. Note that most of the T3 and RT3 are formed from T4 deiodination in the tissues, and only small amounts are secreted by the thyroid.

THE AVARAGE DISTRIBUTION OF IODINATED COMPOUNDS IN THE NORMAL HUMAN THYROID

   

MIT 23 % DIT 33 % T4 35 % T3 7 % (Ganong Review of Medical Physiology 21st ed. 2003)

PLASMA LEVELS OF THYROID HORMONES 

Total plasma T4 : 8 ug/dL (103 nmol/L)



Total plasma T3 : 0.15 ug/dL (2.3 nmol/L)



Large amount of both are bound to plasma proteins (Protein-Bound Iodine / PBI) • PBI - T4 : 7.998 ug/dL (99.98 %) • free T4 : 0.002 ug/dL ( 0.02 %) • PBI - T3 : 0.15 ug/dL (99.98 %) • free T3 : 0.0003ug/dL ( 0.02%)

PLASMA PROTEINS THAT BIND THYROID HORMONES (1) Albumin (TBA) 13%

3500 mg/dL

PBI - T4

PBI - T3 53% (2) Prealbumin (TBPA)

(3) Globulin (TBG) 67%

15 mg/dL PBI - T4 20% PBI - T3 1% 2 mg/dL

PBI - T4

PBI - T3 46%

Distribution of T4 in the body. The distribution of T3 is similar. The dashed arrow indicates inhibition of TSH secretion by increases in the free T4 level in ECF. Approximate concentrations in human blood are shown in parentheses.

Temprature regulatory centers

Environmental Influences

Other brain centers

Hypothalamus

(-)

(-) TRH

Anterior pituitary

(-)

TSH Iodide

Thyroid gland T3 & T4

Heat production

Biological effects

Metabolism of CH, proteins, and fats

Primary steps involved in regulating thyroid hormone production

REGULATION OF THYROID SECRETION



Hiypothalamus - Hypophysis - Thyroid axis



Feed back mechanisms



Environmental influences:  Temperature  Stress

EFFECTS OF THYROID HORMONES (1) Calorigenesis (2) Increase cardiac output (3) Increase oxygenation (4) Effects on carbohydrate metabolism (5) Effects on lipid metabolism (6) Effects on protein metabolism (7) Promote normal growth (8) Promote development and maturation of nervous system

PHYSIOLOGIC EFFECTS OF THYROID HORMONES Calorigenic Action





Increase O2 consumption of metabolically active tissues, except adult brain, testes, uterus, lymph nodes, spleen, and anterior pituitary.



Some effect is due to fatty acids metabolism.



Increase membrane-bound Na+-K+ ATPase activity.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES 

Effects Secondary to Calorigenesis •

Increased nitrogen excretion: endogenous protein and fat stores catabolism  weight loss (if food intake is not increased).

•

Large doses of thyroid hormones: 



extra heat production  slight increase in body temperature  heat dissipating mechanism  cutaneous vasodilatation  decreased peripheral resistance. thyroid hormones + catecholamines  increased cardiac output + cardiac rate, shortened circulation time.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES 

Effects Secondary to Calorigenesis  Large doses of thyroid hormones:  increased need for vitamins  precipitation of vitamin deficiency. •

Small / low doses of thyroid hormones:  decreased hepatic carotene conversion to vitamin A  carotenemia  yellowish tint of the skin (without yellow scleras).  accumulation of skin proteins combined with polysaccharidas, hyaluronic acid, and chondrotin sulfuric acid  water retention and puffiness of the skin (myxedema).  decreased milk secretion.  abnormalities in menstrual cycle and fertility.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES 

Effects on the Nervous System 

Probably are secondary to increased responsiveness to catecholamines  increased activation of the reticular activating system.



Brain development: cerebral cortex and basal ganglia, and cochlea  hypothyroidism during development: mental retardation, motor rigidity, deaf-mutism.



Slow mentation and elevated CSF protein in hypothyroidism.



Rapid mentation, irritability and restlessness in hyperthyroidism.



Brain converts T4 to T3.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES Relation to Catecholamine 

Intimate interrelated action of thyroid hormones and catecholamines.



Increased metabolic rate effect, stimulation effects on nervous system, cardiovascular effects of epinephrine are similar to those of thyriod hormones.



Catecholamines toxicity is markedly increased when treated with T4.



Hyperthyroidism sign and symptom (cardiovascular, tremulousness, sweating) are abolished by sympathectomy, and reduced by drugs that block beta-adrenergic receptors (e.g. propranolol).



Beta blockers are used in thyrotoxicosis treatment.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES 



Effects on the Heart 

Increased number and affinity of beta-adrenergic receptors in the heart  increase its sensitivity to inotropic and chronotropic effects of catecholamines.



Increased number of alpha-MHC (myosin heavy chain) in the atria.

Effects on Skeletal Muscle 

Increased protein catabolism in skeletal muscle  muscle weakness (thyrotoxic myopathy) in hyperthyroidism.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES 

Effects on Carbohydrate Metabolism 



Increased carbohydrate absorption from gastrointestinal tract  in hyperthyroidism: rapid rise in the plasma glucose level after a carbohydrate meal, sometimes exceeding the renal threshold.

Effects on Cholesterol Metabolism 

Increased formation of LDL receptors in the liver  increased hepatic removal of cholesterol from the circulation  lower circulating cholesterol levels before the metabolic rate rises (independent of the stimulation of O2 consumption).

PHYSIOLOGIC EFFECTS OF THYROID HORMONES 

Effects on Growth 

Essential for normal growth and skeletal maturation



Necessary for the normal growth hormone secretion



Potentiate the effect of growth hormone on the tissue



In hypothyroid children, bone growth is slowed and epiphysial closure is delayed.

THE THYROID HORMONES 



Hyposecretion causes: 

mental and physical slowing



poor resistance to cold



in children: mental retardation and dwarfism

Hypersecretion leads to: 

body wasting



nervousness



tachycardia



tremor



excess heat production

HYPERTHYROIDISM

•

Excess secretion of thyroid hormones

•

Increased heart rate

•

Weight loss

•

Highly responsive to stimuli

HYPOTHYROIDISM •

Deficiency in thyroid hormones production

•

Defect in  Thyroid gland itself, hypopthalamus, hypophysis

•

Slower metabolic rate

•

Reduced rate of heat production

•

Intolerance to cold temprature

•

Myxedema

•

Decreased cardiac output

•

Slowing of intellectual functions

•

Lethargy

•

Speech impairment

Thank You