Endocrine Control of Calcium Metabolism Flashcards
What is the distribution of calcium in the body?
- 99% in bone
- 0.9% in ICF
- 0.1% in ECF
What is calcium tightly regulated with?
phosphorous obtained from the diet
What is phosphorus essential for?
- ATP
- cAMP second messenger systems (phosphorylation) - the backbone of DNA molecules
What are the 3 fractions of calcium in the ECF?
- free (ionised) - 50%; biologically active
- complexed (with PO43-) - 5%; not free to participate in chemical reactions
- bound (to protein) - 45%; restricted to the plasma
What is bone?
a living tissue that gets remodelled ~every 10 years
What are the 3 types of bone cell?
- osteocytes
- osteoclasts
- osteoblasts
What do osteocytes do?
transfer calcium to the ECF without destroying the bone structure (essentially retired osteoblasts)
What do osteoclasts do?
secrete hydrochloric acid that dissolves Ca3(PO4)2 crystals (to release calcium and phosphate back into the ECF) and enzymes that break down the organic matrix
What do osteoblasts do?
secrete organic matrix (osteoid) within which Ca3(PO4)2 crystals precipitate
What do osteoblasts act as?
a reservoir of calcium that can be released into the blood circulation when required
What are the 3 steps of resorption?
- osteoclasts anchor themselves to the surface of the bone which creates a microenvironment under the cell (sealed zone)
- within the zone, the osteoclasts create an acidic environment that dissolves the bone’s mineral content
- once the content is dissolved, enzymes released from osteoclasts remove the remaining collagenase bone matrix to compete resorption
What happens after resorption?
osteoblasts move into the resorption space and start to produce osteoid which then forms a scaffold in which calcium and phosphate crystallise
What are the 2 fates of osteoblasts?
- some are trapped in the matrix and become osteocytes
- some undergo apoptosis or revert back to lining cells which cover the surface of the bone
What is bone modelling?
when bone formation by osteoblasts occurs without prior bone resorption by osteoclasts which results in an increase in bone mass
What are early signs of hypocalcaemia?
- Trousseau’s sign
- Chvostek’s sign
How do you do test for Trousseau’s sign?
- a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure (>120mmHg) and held in place for 3 minutes to occlude the brachial artery
- in the absence of blood flow, the patient’s hypocalcaemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm
- the wrist and metacarpophalangeal joints flex, the DIP and PIP joints extend, and the fingers adduct
How do you do test for Chvostek’s sign?
- begin by telling the patient to relax his facial muscles
- stand directly in front of him and tap the facial nerve either just anterior to the earlobe and below the zygomatic arch or between the zygomatic arch and the corner of the mouth
- a positive response varies from twitching of the lip at the corner of the mouth to spasm of all facial muscles depending on the severity of the hypocalcaemia
What are the 7 main physiological functions of calcium?
- membrane excitation
- EC coupling
- haemostasis
- stimulus-secretion coupling
- second messenger and enzyme activity
- maintenance of tight junctions between cells
- bone formation
What are the effects of low calcium levels in skeletal muscle?
voltage gated sodium channels stay open and more sodium diffuses through the membrane which causes excess depolarisation and impulses are transmitted repeatedly which can lead to increased skeletal muscle contraction
What are the effects of low calcium levels in cardiac muscle?
decreased cardiac muscle contraction which leads to abnormal heart rhythms
What does the entry of calcium into secretory cells allow?
the release of the secretory product by exocytosis
What are the 3 hormones responsible for calcium regulation?
- PTH
- vitamin D
- calcitonin (CT)
What is PTH?
an 84 AA protein polypeptide secreted by the chief cells of the parathyroid gland
What organs does PTH have an effect on?
bone, intestines and kidneys
What is the secretion of PTH triggered by?
a decrease in free ionised calcium in the ECF
What is the relationship between calcium and PTH levels?
inverse linear
What happens if PTH levels increase?
both calcium and phosphate levels would decrease; they would crystallise in bone or soft tissues as calcium phosphate
What effect does increased PTH levels have on the kidneys?
- decreased phosphate reabsorption
- increased calcium reabsorption
- increased vitamin D formation
What effect does increased PTH levels have on the bone?
increased resorption
What would complete absence of PTH lead to?
death from hypocalcaemic tetany within a few days
What is calcitonin?
a 32 AA peptide secreted by the parafollicular cells of the thyroid gland
What is the relationship between CT and calcium levels?
positive linear
What does CT act to do?
fine-tune the calcium regulatory system; it lowers the plasma calcium concentration but is not important in the normal control of calcium metabolism
What effect does increased CT levels have on the kidneys?
- ↓ phosphate reabsorption
- ↓ calcium reabsorption
What effect does increased CT levels have on the bone?
↓ resorption
What does a drop in phosphorous levels lead to?
an increase in calcium levels which tells the parathyroid to stop making hormones and the kidneys then increase calcium excretion
What can phosphorus disorders arise from?
not enough phosphorous in the diet, diabetes and alcoholism
What are the 2 main sources of vitamin D?
- diet (vitamins D2 and D3 are absorbed along with lipids mainly from fish, liver and milk)
- skin (UV radiation from sunlight can convert cholesterol derivative into D3 in the skin)
What are the active metabolites of vitamin D3?
calcidiol and calcitriol
What is the relationship between plasma calcium levels and vitamin D3?
inverse linear
What is the time for sufficient daily intake of vitamin D
10 mins
What are the 4 steps of vitamin D synthesis?
- 7-dehydrocholesterol in the skin is exposed to UV radiation to produce biologically inactive cholecalciferol
- an OH group is added by liver enzymes to produce 25-OH-vitamin D3 (calcidiol) which is stored in the hepatocytes until needed
- another OH group is added by kidney enzymes to produce active 1,25-(OH)2-vitamin D3 (calcitriol)
- active D3 travels to the intestine and promotes calcium and phosphate absorption
How much more biologically active is active D3 than calcidiol?
100-500x greater
What are the roles of the kidney, intestine and bone in calcium regulation?
- kidney reabsorbs calcium
- intestine increases calcium absorption
- bone increases resorption to release calcium
What can too much calcium arise from?
abnormal levels of PTH or hyper-parathyroidism
What are the clinical symptoms of hypercalcaemia/hypophosphataemia?
- moans - depression, anxiety, cognitive dysfunction, insomnia
- bones- bone pain
- stones - increased incidence of kidney stones
- thrones - polyuria
- groans - abdominal pain, nausea and vomiting
What is polyuria?
abnormally large volumes of dilute urine since calcium impairs sodium water reabsorption
How much calcium can the body filter at once?
~600mg
What are the treatment options of kidney stones?
- small - drink water to relive pain or take drugs to help pass the stones
- large - use of sound waves to break up stones, surgery
Why is the drop in bone mass more pronounced in females?
oestrogen, which prevents bone resorption, levels decrease with age
What can reduced PTH secretion be caused by?
removal/destruction of the gland inadvertently or by surgery
What can hypocalcaemia/hyperphosphataemia be treated by?
- synthetic PTH (not actually available)
- vitamin D (active form) and a high calcium diet (risk of kidney stones and increased risk of chronic kidney diseases)
What can a vitamin D deficiency lead to?
impaired intestinal absorption of calcium
How can hypocalcaemia affect bones?
- PTH secretion is stimulated to maintain plasma calcium at the expense of the bones which leads to the bone matrix not properly mineralising
- the bone therefore becomes soft and deformed due to the pressures of weight bearing
- in children, this is called Rickets and in adults it is Osteomalacia
