thyroid hormones · renal function muscle mass adipose tissue thermogenesis sweating insensible...
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Learning Objectives
By the end of lecture, the students should be able to:• Describe the functional anatomy of thyroid gland• Briefly describe the mechanism of synthesis of thyroid
hormones• Discuss the functions of thyroid hormones• Explain the regulation of thyroid hormones• Describe the effects of abnormal secretion of thyroid
hormones
▪ Primary hormone secreted by thyroid gland is thyroxine▪Much lesser amount is tri-iodothyronine(T3)▪ T3 has much greater biological activity(more rapidly acting,5 times potent)▪ T3 Specifically generated at sites of action by deiodination of T4
Transport of thyroid hormones
• 99% of T3 and T4 combines immediately with plasmaproteins as
• Thyroxine binding globulin• Thyroxine binding prealbumin & albumin
• Slow release• Slow onset & long duration of action
What are non-genomic actions of thyroid hormones?
These are independent of gene transcription
• On Heart, pituitary and adipose tissue• Very quick effects• Regulation of ion channels/oxidative phosphorylation• May involve cAMP second messenger system
Generalized effects of thyroid hormones
➢ Calorigenic effects
➢ Sympathomimetic effects
➢ Growth promoting effects
1. Calorigenic effects:
❑ Increase metabolic activities of almost all tissues of the body → BMR increases to 60 to 100% above normal.
This is because;
▪ ↑ O2 consumption
▪ ↑ Na-K ATPase
▪ ↑ number and activity of mitochondria
❑ The rate of utilization of foods for energy is
greatly accelerated by:
▪ ↑ carbohydrate absorption from gut
▪ ↑ gluconeogenesis
▪ ↑ glycogenolysis
▪ ↑ lipolysis (increased mobilization
and metabolism of fatty acids)
T4
T3
T3TR
mRNA
Proteins for growth and
maturation
Na+, K+- ATPase MitochondriaRespiratory enzymes
O2 Consumption Metabolic rate
CO2UreaVentilation
Renal FunctionMuscle Mass
Adipose Tissue
Thermogenesis
Sweating
Insensible water loss
SubstratesO2
Cardiac Output
Ventilation
Food Intake
Mobilization of stored fat, carbohydrates and Proteins
Other enzymes, proteins
Nucleus
Cytoplasm
Whole Body Effects
(permissive)
Tissue deiodinase
Intracellular Effects
ATP use
Effects secondary to calorigenesis:
➢When the metabolic rate is increased by T3 and T4,nitrogen excretion is increased. If food intake is not increased, endogenous protein and fat stores are catabolized and weight is lost.
➢ Increased metabolic rate causes increased need for all vitamins → vitamin deficiency syndromes
2. Sympathomimetic effects:
▪ Functional synergism▪ Increased number of β- adrenergic receptors▪ Enhanced responses to circulating catecholamines▪ Treatment of thyroid storm by beta blockers
3. Effects on growth:
Thyroid hormones has both general and
specific effects on growth. Also potentiate
the effects of growth hormones on tissues.
➢ Increased responsiveness to catecholamines
➢ Most effects are on cerebral cortex and basal ganglia➢ Reaction time of stretch reflexes shortened
in hyperthyroidism
Effects on Nervous system:➢ Growth and development of brain during fetal life
and for first few years of Postnatal life.➢ Insufficient thyroid secretion by fetus →
retarded growth and maturation of brain
Specific effects of thyroid hormones
Central nervous system:
Increased responsiveness to catecholamine↓
↑ activation of RAS↓
Irritability, restlessness, inability to sleep in hyperthyroidism
(Exhausting effect on musculature- constant tirednessBut excitable effect on synapses)
Skeletal growth:
▪ Thyroid hormones promote normal growth and Skeletal development.▪ In hypothyroid growing children, growth isretarded.▪ In hyperthyroidism, excessive skeletal growth,early maturation of bones, early closure of epiphysis
Effect on skeletal muscles:
1. Slight increase in levels cause increased muscle strength but excess hormone causes protein catabolism -muscle weakness (Thyrotoxic myopathy)
2. Increased reactivity of neuronal synapses in muscle tone controlling areas of spinal cord cause FINE MUSCLE TREMORS
Effects on metabolism
▪ Carbohydrate metabolism
➢ Rapid uptake by cells
➢ Enhanced glycolysis➢ Enhanced gluconeogenesis➢ Increased absorption from GIT➢ Increased Insulin secretion
➢Effects vary with increased or decreased thyroid levels
▪ Fat metabolism:
➢ ↑ mobilization of fats from fat stores➢ ↑ free fatty acid conc. in plasma➢ ↑ oxidation of fatty acids by cellsIncreased thyroid hormone decreases the conc.of cholesterol, phospholipids and triglycerides in plasma.
Heat Production and CO2
in tissues
Peripheral vascular resistance
Diastolic Blood pressure
Reflex in Adrenergic Stimulation
Indirect
Cardiac Muscle:
◼ b-Adrenergic Receptor Density
◼ Direct effect on excitability of heart
◼ Increased heart strength by
a Myosin heavy chain isoform
Increased Na+, K+ ATPase
Ventricular contractility
and function
Direct
Cardiac Heart Rate and Contractility
Effects on cardiovascular system
Mean arterial pressure remains normal
Pulse pressure increased because of increased blood
Flow
Respiration:
Increased due to increased oxygen utilizationand CO2 formation
Gastrointestinal function:
▪ Increased secretion of digestive juices▪ Increased motility
Sexual functions:
▪ Normal hormonal level is required for normal sexual function
▪ Deficiency or excess cause abnormal function
Effects of TSH on thyroid gland
❑ Increased proteolysis of thyroglobulin❑ Increased activity of the iodide pump-iodide trapping❑ Increased iodination of tyrosine to form thyroid
hormone❑ Increased size and increased secretory activity of
thyroid cells❑ Increased number of thyroid cells and increased
secretory activity
Activation of cAMP second messenger system
Effect of cold & neurogenic stimuli on TRH & TSH
• Excitation of temperature regulating center of hypothalamusby cold exposure
TRH
TSH
Thyroid hormones
Increased basal metabolic rate
❑ Thiocyanate ions decrease iodide trapping bycompetitive inhibition
❑ Propylthiouracil decreases thyroid hormone formation
• Block the peroxidase enzyme• Block coupling of iodinated tyrosines
❑Iodides in high concentration decreases all activities of thyroid gland & decreases size
Diagnostic tests for hyperthyroidism
1. Basal metabolic rate BMR is +30 to +602. TSH levels are suppressed3. TSI (Thyroid stimulating immunoglobulins) are
increased
Treatment:• Thyroidectomy• Radioactive Iodine for hyperplastic gland
Hypothyroidism
• Hashimoto’s disease -Autoimmunity that destroys the gland
• Endemic colloid goiter caused by dietary Iodidedeficiency
• Idiopathic non-toxic colloid goiter- thyroiditisAbnormalities of enzyme systems
Myxedema
• Almost total lack of thyroid function • Excessive tissue gel in interstitial
spaces• Non-pitting edema• Atherosclerosis
Diagnostic tests for hypothyroidism
• Thyroxine levels are low• TSH levels are extremely high (in response to
test dose of TRH)• BMR is -30 to -50
Treatment
• Oral thyroxine
Cretinism
Extreme hypothyroidism during fetal life, infancy orChildhood• Failure of body growth• Mental retardation
❑ Congenital cretinismcongenital lack of thyroid gland
❑ Endemic cretinismFailure of thyroid gland toproduce thyroid hormones-genetic defect or lack of iodine
Features of cretinism
• Sluggish movements• Physical & mental retardation• More effect on skeletal growth then soft tissues so
disproportionate growth - obese, stocky, short appearance
• Tongue sometimes becomes very enlarged- obstructsswallowing & breathing- guttural breathing