Endocrine Physiology Flashcards
Outline the steps in the manufacture of thyroid hormones
all occurs on/within thyroglobulin molecule - also stores the thyroid hormones
The basic ingredients for thyroid hormone synthesis are tyrosine & iodine - need to consume iodine in diet but don’t need to consume tyrosine in diet cuz its made by body
Iodine ( I ) + tyrosine = monoiodotyrosine (MIT)
MIT + I = diiodotyrosine (DIT)
DIT + DIT = thyroxine (T4) - this is a thyroid hormone
DIT + MIT = triiodothyronine (T3) - thyroid hormone (names are derived from number of iodine atoms attached)
Synthesis and secretion:
(1)iodide trapping by the thyroid follicular cells (Na+/I- symporter). Iodides (I–) are actively taken into the cell against concentration gradient.
(2) diffusion of iodide to the apex of the cells.
(3) transport of iodide into the colloid.
(4) oxidation of iodide to iodine (TPO (thyroid peroxidase) enzyme; H2O2 oxidant)
(5) incorporation of iodine into tyrosine residues within thyroglobulin molecules in the colloid (iodination of tyrosines). Forms MIT and DIT.
(6) combination of two DIT molecules to form tetraiodothyronine (thyroxine, T4) or of MIT with DIT to form triiodothyronine (T3): coupling. Because all these reactions occur within the thyroglobulin molecule, all the products remain attached to this protein.
Thyroid hormones remain stored in this form (with the thyroglobulin) until they are needed.
(7) endocytosis: uptake of thyroglobulin from the colloid into the follicular cell, fusion of the thyroglobulin with a lysosome (hydrolysis), and proteolysis and release of T4, T3, DIT, and MIT
(8) release of T4 and T3 into the circulation
(9) deiodination of DIT and MIT to yield tyrosine and the free iodine is recycled for synthesis of more hormones
All steps of hormone manufacture take place on the thyroglobulin molecules within the colloid.
Describe the structural and functional differences between T3 and T4
T4 needs to be converted to T3 to exert its full biological activity - 5’deiodinase-I does this - in liver kidney
DIT + DIT = thyroxine (T4) - this is a thyroid hormone
DIT + MIT = triiodothyronine (T3) - thyroid hormone (names are derived from number of iodine atoms attached)
Describe the metabolic effects of thyroid hormones
Metabolic:
- Increase O2 consumption
- Increase BMR
- Calorigenic effect - increase no. of enzymes - enhance metabolic activity - burn more calories
Carbohydrate metabolism:
- increased absorption of glucose from GIT
- increased insulin secretion
- increased gluconeogenesis
- glucose oxidation, glycogen degradation (hypersecretion)
Lipid metabolism:
- lipolysis - increases circulating FFA levels, accelerates FFA oxidation
- decrease cholesterol, triglycerides & phospholipids in plasma (hypersecretion) - lipid lowering and antiobestiy effect
Protein metabolism:
- protein synthesis
- breakdown (hypersecretion)
Explain how the hypothalamus and pituitary regulate circulating levels of thyroid hormones
see slide 11 of thyroid lecture
cold (especially in infants) causes an increase in thyroid hormone secretion
stress has a negative impact on synthesis and secretion of thyroid hormone
hypothalamus secretes thyroid releasing hormone - acts on anterior pituitary gland - produces thyroid stimulating hormone - acts on thyroid gland - causes release of two thyroid hormones - then get various physiological actions
- when the level of hormones gets to the right level
- causes switching off of release of TSH and TRH from pituitary and hypothalamus
- this is negative feedback control
Describe the systemic effects of thyroid hormones
Heart:
- increase HR, CO, SBP and decrease DBP
- Increased blood flow to skin - as a result of the thermogenesis
Lungs:
- increase ventilation rate - because more CO2 produced as a result of increased metabolic rate
GIT:
- Increases appetite
- Increases secretion digestive juices
- Increases GIT motility
- can lead to diarrhoea
Reproductive:
- Essential for normal reproduction and lactation
Musculoskeletal :
- promotes normal body growth and maturation of skeleton - through alternating actvity of osteoblasts and clasts
- promotes normal function and development of muscles
Nervous system:
- promotes normal neuronal development in feotus and infant (developmental actions of thyroid hormone) - thyroid becomes active very early in life - as early as 11 weeks
- promotes normal neuronal function in adult - increases synaptic activity
- enhances effects of sympathetic nervous system – sympathomimetic: upregulates β1 adrenergic receptors in heart
describe the causes of hyperthyroidism
Autoimmune disease – Grave’s disease - most common cause
Thyroid adenoma
Inappropriate TSH secretion (rare)
describe the symptoms and signs of thyroid hormone abnormality (hyper and hypo)
Hyper:
- increased basal metabolic rate
- weight loss, good appetite
- anxiety, physical restlessness, mental excitability
- hair loss
- tachycardia, palpitations, atrial fibrillation
- warm sweaty skin, heat intolerance, diarrhoea
- exophthalmos in Grave’s disease
Hypo:
- decreased basal metabolic rate
- weight gain, anorexia
- depression, psychosis, mental slowness, lethargy
- dry skin, brittle hair
- bradycardia
- dry cold skin, prone to hypothermia
- constipation
describe how The hypothalamic-pituitary thyroidal axis is affected by thyroid disorders
- Primary hypothyroidism - decrease T4
- increase in TSH and TRH - Pituitary hypothyroidism (2y hypothyroidism)
- decrease T4 and TSH
- increase TRH - Hypothalamic hypothyroidism (3y hypothyroidism)
- decrease in T4, TSH and TRH - Grave’s disease
- increase T4
- decrease I TSH and TRH
describe how The hypothalamic-pituitary thyroidal axis is affected by thyroid disorders
see slide 18 of thyroid lecture
- Primary hypothyroidism - decrease T4
- increase in TSH and TRH - Pituitary hypothyroidism (2y hypothyroidism)
- decrease T4 and TSH
- increase TRH - Hypothalamic hypothyroidism (3y hypothyroidism)
- decrease in T4, TSH and TRH - Grave’s disease
- increase T4
- decrease I TSH and TRH
describe primary hyperaldosteronism
Conn’s syndrome
adrenal ademnoma
- hypertension
- hypokalemia
- hypervolemia
- metabolic alkalosis
describe secondary hyperaldosterism
relates to problem outside of adrenal gland
overactivity of the renin-angiotensin system
describe adrenocorticol insufficiency/hypofunction
Primary adrenocortical insufficiency – Addison’s disease
- Destruction of both Adrenal Cortices
Lack of glucocorticoids: hypoglycaemia reduction in fat & protein metabolism loss of weight poor exercise tolerance poor stress tolerance - DEATH
Lack of MINERALOCORTICOIDS: - ￬ Na +; ￪ K+ and H+
- ￬ Blood Volume
- ￬ Cardiac Output – DEATH
Lack of ADRENAL ANDROGENS
Secondary or tertiary adrenocortical insufficiency – due to a pituitary or hypothalamic abnormality - results in insufficient ACTH
- can be due to sudden withdrawal of glucocorticoid drugs; failure to increase glucocorticoids during stress
describe the symptoms of Addisons disease
bronze pigmentation of skin changes in distribution of body hair go distrubances weakness hypoglycemia postural hypotension weight loss
describe the symptoms of Addisons disease
bronze pigmentation of skin changes in distribution of body hair GI distrubances weakness hypoglycemia postural hypotension weight loss
compare and contrast the effects of the catecholamines and SNS activity
Adrenal stimulation:
- exerts its effects in all cells
FINSIH SLIDE
