Metabolism Flashcards
Functions of thyroid hormones
Normal growth development
Metabolic activity and oxygen requirements
Lipid and carb metabolism
Embryology of thyroid
Week 4: thyroid appears from endodermal tissue
Week 5: thyroglossal duct breaks down and gland decends
Week 7: thyroid migrates anterior to trachea
Week 10: thryoglossal duct disappears
Week 12–20: thyroid functional
Week 20–26: thyroid independent
Lingual thyroid
Failure of thyroid to migrate during development
Thyroglossal cyst
Remnant of thyroglossal duct that didn’t break down
Can be seen moving up when patient protrudes tongue
Anatomy of thyroid
Deep to sternohyoid
Anterior to recurrent laryngeal nerve and trachea cartilage rings 2 and 3
Right to oesophagus
Blood supply of thyroid
Superior thyroid artery from external carotid artery
Inferior thyroid artery from subclavian artery (thyrocervical trunk)
Medullary thyroid cancer
Aggressive cancer that secretes calcitonin
Thyroglobulin
Storage form of T3/4 found in colloid of the thyroid
Describe the process of T3/4 release
1) Iodine uptake into bloodstream is oxidised to iodide
2) Iodide rapidly incorporated into tyrosine molecules in follicular cells, then into thyroglobulin
3) At lumen interface, remaining iodide is catalysed to MIT and DIT by thyroid peroxidase (which required H2O2) and is stored in colloid as thyroglobulin
4) TSH from AP reaches follicular cell membrane which scallops in to allow endocytosis of “colloid drops” containing thyroglobulin and releases T4/3 into capillary
Locations of NIS
Breast Salivary glands Ciliary body of eye Gastric mucosa Differentiated thyroid cancer cells
Symptoms of thyrotoxicosis
Nervousness Sweating Weight loss Heat sensitivity Tachycardia Weakness Goitre Skin changes Tremor Eye signs e.g., in Graves
Causes of thyrotoxicosis
Thyroiditis Graves Amiodarone Iodine Thyroxine Toxic nodule
TSH and T4 levels in primary hypothyroidism
TSH will be high and T4 will be low
TSH and T4 levels in secondary hypothyroidism
TSH will be normal or low and T4 will be low
TSH and T4 levels in primary hyperthyroidism
TSH will be low and T4 will be high
TSH and T4 levels in secondary hyperthyroidism
TSH will be high and T4 will be high
NIS
Sodium iodine transporter
Iodide concentration in plasma is extremely low so it is “trapped” by NIS
Active transporter that exchanges 2 sodium ions for 1 iodide ion against its concentration gradient
Parathyroid hormone functions
Stimulates osteoclastic bone resporption
Stimulates renal tubular reabsorption of calcium
Stimulates gut absorption of calcium by acting on the kidney to convert calcidiol to calcitriol
3 things that can regulate PTH release
Serum ionized calcium
Serum phosphate
Serum 1,25 dihydroxyvitamin D
ECF calcium
45% ionised, bioactive
10% complexed with anions
45% protein-bound
Describe how PTH is released into the ECF
Calcium present in food enters the stomach. Magnesium acts as a cofactor to uptake calcium via the transmembrane calcium receptor. Calcium is uptaken into the parathyroid chief cell which activates PTH to be released into the ECF.
Basic vitamin D metabolism
Sunlight absorbed by skin, which makes calciferol (also from diet)
Calcirefol is hydroxylated by the liver to make calcidiol
Calcidiol moves to the kidney where it is metabolised via PTH to calcitriol
Calcitriol uptaken by the kidney tubules, increasing calcium and phosphate absorption
Parathyroid hormone-related peptide
Important paracrine regulator of breast, skin and bone
Produced in excess by some cancers, leading to hypercalcaemia (acts very similarly to PTH)
Primary hyperparathyroidism
Overactive parathyroid gland causing bone breakdown and increased reabsorption of calcium
Causes PTH-dependent hypercalcemia
Examples of vitamin-D dependent causes of hypercalcaemia
Sarcoidosis – granulomas express high levels of 1α-hydroxylase, the enzyme that catalyzes the hydroxylation of 25-OH vitamin D to its active form which increases calcium and phosphate reabsorption
Vitamin D intoxication
Hypoparathyroidism
Causes hypocalcaemia due to reduced release of PTH and therefore decreased absorption and resorption of calcium
Can be caused by many things, including surgery, radiation, autoimmune disease, infiltrative diseases etc.
Pseudohypoparathyroidism
Parathyroid hormone resistance
PTH levels will be high, calcium levels low and phosphate levels high
Causes of hypoparathyroidism due to abnormalities of vitamin D metabolism
Vitamin D deficiency/resistance
Renal failure
Deficient
1α-hydroxylation
PTH influence on phosphate
Promotes excretion of phosphate in urine and pulls it out of bone along with calcium
Phosphatonins
Specifically regulate renal handling of phosphate, therefore causes phosphate wasting
Causes of hyperphosphataemia
Increased input e.g. IV phosphate, cell death
Decreased excretion e.g. renal failure, PTH deficiency
Causes of hypophosphataemia
Inadequate GI absorption e.g. due to vitamin D deficiency
Respiratory alkalosis
Renal loss
How do phosphatonins contribute to hypophosphataemia?
FGF23 (derived from bone) inhibits the hydroxylation of inactive form of vitamin D and decreases sodium phosphate reabsoprtion in the kidney
Together, there is an overall decrease in phosphate absorption leading to hypophosphataemia
Osteomalacia
Failure of bone to mineralise
Accumulation of unmineralised osteoid
Can be calciopenic, phosphopenic or due to osteoblast dysfunction
Autosomal Dominant Hypercalciuric Hypocalcaemia
Constitutive activation of calcium sensing receptor
Parathyroids read plasma ionised calcium level as being higher than it really is, so PTH level is inappropriately low for a given calcium level
No real treatment, can give small doses of vitamin D if recurrent symptoms are present
