The parathyroid gland (calcium and phosphate regulation) Flashcards
Adult human contains around ……… of calcium
1000g
99% of calcium is sequestered in
bones as hydroxyapatite crystals (Ca10(PO4)6(OH)2)
how much calcium is exchanged between bone and ECF each day
300-600 mg
skeleton provides
- Structural support
- Major reserve of calcium
- Helps to buffer serum levels
- Releasing calcium phosphate into interstitium
- Up taking calcium phosphate
serum calcium
2.2-2.6 mH
calcium is distributed between three itner convertible fractions
- Mostly ionised calcium
- Protein bound calcium
- Complexed calcium (pi, citrate etc)
role of calcium
- Builds and maintains bones and teeth
- Heart rhythm
- Eases calcium
- Assists normal blood clotting
- Normal nerve function
- Normal kidney function
- Lowers BP
- Activity of some enzymes
- Intracellular signalling
- Nervous transmission at NMJ
calcium and clotting
Calcium is an important clotting factor – Factor IV
what is used in blood tests to stop blood clotting
EDTA- calcium chelator –> stops the blood clotting
what is used to chelate calcium in donor blood
citrate
- Citrate levels may become high in patients blood
- Will need to give recipients of massive blood transfusions intravenous calcium
which hromones regulate calcium and phosphate
parathryoid hormone (PTH)
calcitriol
calcitonin
Parathyroid hormone (PTH)
produced and released by the parathyroid gland
- secretes in response to low plasma calcium
- affects bone, intestines and kidney
calcitriol
released by the kidney from vitamin D
- increases plasma calcium
calcitonin
released from the thryoid parafollicular cells
- decreases plasma calcium and phosphate
- minor role
the parathryoid
4 sit on the thyroid
- Unique appearance
- Doesn’t look like a normal gland
- Capsule around parathyroid gland
- 2 cell types
- Chief cells- produce parathyroid
- Oxyphil- not sure what they do (maybe old chief cell)
the parathryoid can be accidentally
Removed during thyroid surgery
- Important to try and preserve - regularly monitor serum calcium
PTH synthesis
- Synthesis regulated both by transcriptional and post transcriptional levels
- Low serum calcium unregulated gene transcription
- Low serum calcium prolongs survival of mRNA
- High serum calcium down regulates
features of PTH synthesis
- No serum binding protein
- Straight chain polypeptide hormone - preprohormone (115AA long), cleaved to 84AA
PTH continually syntheses but little stored
- Chief cells degrade hormone as well as synthesis it
- Cleavage of PTH in chief cell accelerated by high serum calcium levels
PTH affect on bones
Activates osteoclasts- calcium and phosphate released into the blood
PTH affect on intestines
- Activates Vitamin D to become calcitriol and hence increases trans cellular uptake from GI tract
- GI tract can absorb more calcium
PTH and the kidney
- increases reabsorption of calcium
- PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine.
*However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone*
kidney stones
Calcium + Phosphate forms hydroxyapatite crystals which causes stonesà don’t want to have a peak of calcium and phosphate at the same time- therefore body has adapted to increase calcium (reabsorption), and increase phosphate excretion. Whilst PTH causes phosphate to be released from bone and increased absorption in the intestines, there is a net loss of PO4 as the loss in urine will always be greater than that gained from bones.
bone deposition is mediated by
0steoblasts which produce collagen and matrix which is mineralised to hydroxyapatite
bone reabsorption is mediated by
osteoclasts
- produced acid micro-environment dissolving hydroxyapaptite releasing calcium and phosphate into the blood (PTH stimulates osteoclasts)
PTH has a quick action on the bone
- 1-2 hrs PTH stimulates osteolysis
- PTH induces osteoblastic cells to synthesis and secrete cytokines on cell surface
- Cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis
- PTH decreases osteoblasts activity exposing bone surface to osteoclast
- Reabsorption of mineralised bone and release of Pi and Ca2+ onto extracellular fluid
Calcitriol (1,25(OH)2D) physiological role
Release of calcium from bone by enhancing actions of PTH
Absorption of calcium in intestine via vitamin D
Increase reabsorption of ca2+ and phosphate
calcitriole is the active form of
vitamin D normally produced in the kidney
the body makes vitamien D when it is exposed to sun (acts like a hormone)
which foods are fortified with vitamin D
Cheese, butter, margarine, fortified milk, fish and fortified cereals are food sources of vitamin D
synthesis of calcitriol
- Sun stimulates the production of Vitamin D3 in the skin
- Vitamin D3 is converted to 25(OH)D (pre-hormone substrate) in the liver
- 25(OH)D is converted to 1,25(OH)2D (Calcitriol) in the kidney under influence of PTH
physiological action of calcitonin: bone
decreased reabsorption of bone
physiological action of calcitonin: kidney
decreased reabsorption of calcium and phosphate
physiological action of calcitonin: GI
no affect
increased plasma calxcium
decrease PTH secretion
decrease in plasma calcium
increase PTH secretion
symptoms of chronic hypercalcaemia
Stones (hydroxyapatite)
Moans (depression)
Groans (abdominal pains)
Bones (muscle ache)
Tiredness
Dehydration
Constipation
severe hypercalcaemia (>3mmol/L) symptoms
- Polyuria can lead to dehydration which then exacerbates the hypercalcaemia
- Lethargy
- Weakness
- Confusion
- Coma
- Renal failure
- Rehydration mainstay treatment
- In patients with a ligand hypercalcemia and come this is not necessarily terminal event. After rehydration many can turn home
cancer and hypercalcaemia
- Malignant osteolytic bone metastasis
- Multiple myeloma
- Common cancers that metastasize to bone causing lytic lesions and hypercalcemia
- Breast
- Lung
- Renal
- Thyroid
cancer and hyper/hypocalcaemia
Hypercalcaemia is commonly associated with cancer which is usually advanced and portends a poor prognosis. Hypocalcaemia is more often seen as a complication of therapy aimed at reducing skeletal morbidity rather than an effect of the cancer itself
hypocalcaemia
Hypocalcaemia causes hyper-excitability of the neuromuscular junction.
symptoms of hypocalcaemia
Symptoms include pins and needles, tetany, paralysis, and convulsions.
common sites for bone metastasis
Vertebrae
Pelvis
Proximal parts of the femur
Ribs
Proximal part of the jumerus
Skull
More than 90% found in this distribution
lytic lesions causes by metastsies can cause
hypercalcaemia
