Week 6: Endocrine 4: calcium homeostasis and CKD Flashcards
What are the functions of calcium?
Muscle contraction
blood clotting
nerve conduction
Bone mineralisation
Hormonal communication
What is the distribution of total body calcium?
99% is found in the bone
1% is found in body fluids
What is the distribution of calcium in the body fluids?
50% is ionised or free
10% is bound to anions (phosphate)
40% if protein bound (of which 80% is bound to albumin and 20% to globin)
What is the biologically active calcium?
Ionised or free calcium
What is the normal levels of ionised calcium in adults?
4.64 to 5.28 mg/dL
What is meant by adjusted calcium?
Aims to measure the amount of free or ionised calcium only - the active calcium in the body
This is useful when there are extremes in protein bound or anion bound calcium should as hypoalbuliminia that effect total calcium levels but may not effect the levels of active calcium.
What hormones are responsible for the regulation of calcium levels in the blood?
parathyroid hormone
Calcitriol or vitamin D3
Calcitonin
What are the main organs that are involved in the homeostasis of calcium?
Kideny
Bone
Intestines.
What is the most potent regulator of calcium levels in the ECF?
Parathyroid hormone
Where and under what conditions is parathyroid hormone produced?
Produced by parathyroid glands
Cheif cells in the gland
In response to low levels of Ca2+
What is the suggested role of oxyphil cells in the parathyroid gland?
Hypothesised - not known
Suggested to be inacitvated chief cells - rather than undergoing apoptosis become inactive cells.
What are the main mechanisms of parathyroid hormones effect on calcium levels?
Act directly on the kidney
Acts indirectly on the intestine by vitamin D
Acts indirectly on the bones
What is the effect of parathyroid hormone on the kidney?
Directly - increase calcium reabsoprtion so decreased excretion in urine
- decrease phosphate reabsorption leadsing to increased secretion in urine
This leads to increased blood calcium and decreased blood phosphate
Indirectly - increased calcitriol formation - increases levels in the blood stream leading to increased calcium absorption from the small intestine - leading to higher levels of plasma calcium
What are the effects of parathyroid hormone on the bone?
Acts indirectly
Binds to receptors on osteoblasts - causes to proliferate and release RANKL and M-CSF
RANKL and M-CSF binds to receptors on the surface of osteoclasts and activates the osteoclast
The osteoclast secretes acid and lysosomes fuse with the ruffled membrane to release enzymes to the bone.
Bone is reabsopbed (broken down) releasing phosphate and calcium into the blood.
What is the process of vitamin D synthesis?
D3 ( 7-dehydrocholesterol) can be converted to cholecalciferol (D2) in the skin in the presence of UV light
Cholecaliferol can also be obtained. directly by diet
In the liver, 25-hydroxylase enzymes catalysed the first hydroxylation converting into calcidiol.
Travels to the kidney where 1-alpha hydroxylase catalysed the second hydroxylation converting into calcitriol (1,25 -(OH)2- cholecalciferol active vitamin D). This enzyme is promoted in low blood calcium.
Another pathway in the absence of 1-alpha hydroxylase in the kidney converts to an inactive form 24,25 (OH)2-cholecalciferol.
What factors increase the levels of 1alpha hydroxylase enzyme in the kidney?
Decreased plasma Ca2+
Increased circulating levels of PTH
Decreased plasma phosphate concentration.
What are the effects of active vitamin D?
Acts on the intestine to increase absorption of calcium and phosphorus
Act on the kidney to increase calcium retention
Acts on the bone to cause bone reabsorption to release calcium ions and phosphorus.
What is meant by circulating Vitamin D?
Measure of nutritional Vitamin D status - calcidiol**
Where and under what conditions causes the secretion of calcitonin?
Secreted by C cells or parafollicular cells int eh thyroid gland in response to hypercalcemia.
Is a PTH antagonist
What is the action of calcitonin on the body?
Acts directly in the kidneys to decrease calcium reabsorption and decrease phosphate reabsorption - leads to increased urinary excretion of calcium and phosphate
Acts on the bones the inhibit osteoclasts hence decrease bone reasborption.
This leads to a decrease in plasma calcium and phosphate.
What other hormones may contribute to the regulation of bone health?
Calcium-regulating hormones - PTH, calcitonin, calcitriol
Sex hormones - oestrogen, testosterone
Other hormones - growth hormone/insulin like growth factor, thyroid hormone and cortisol
What are the effects of growth hormones on bone health?
Stimulates bone formation and stimulates longitudinal growth
What are the effects of thyroid hormone of bone health?
Too much stimulates bone reabsorption
activates osteoclastic activity
What are the effects of glucocorticoids on bone health?
Inhibits bone formation (inhibits osteoblasts)
Decreases calcium ion absoprtion from the intestines
What is the effect of estrogen and testosterone on bone health?
Maintain bone density by inhibition osteoclasts
Stimulation of osteoblasts
Calcium absorption
Inhibit bone resorption.
What lifestyle factors are important to maintaining bone health?
Calcium intake - especially in childhood, adolescence, pregnancy and lactation
Vitamin D - dietary supplements or sunshine
Regular exercise - muscle strengthening and weight bearing exercise
Avoid smoking and drinking to excess
Maintain a health body weight
Hormonal health
What are the biological markers of primary hyperparathyroidism?
High PTH
High serum calcium
Low serum phosphate
What are the common causes of primary hyperparathyroidism?
Parathyroid tumour
Ectopic parathyroid tissue
What are the symptoms of primary hyperparathyroidism?
Renal stones
Bone bone
Abdominal pain and constipation
Depression
What is the most common treatment for primary hyperparathyroidism?
Parathyroidectomy
What are the key biochemical biomarkers of secondary hyperparathyroidism?
High levels of parathyroid hormone
Low levels of calcium ions
High levels of phosphate
(unable to excrete calcium and phosphate, calcium binds to phosphate decreasing free calcium levels)
What are the common causes of secondary hyperparathyroidism?
Vitamin D deficiency or impaired renal function
End stage kidney disease
What are the common presentations of secondary hyperparathyroidism?
Osteoporosis
Renal stones
Bone and joint pain
What are the common treatments of secondary hyperparathyroidism?
Vitamin D3 supplements (cholecalciferol)
Treat underlying cause of kidney damage.
How does vitamin D deficiency present in children?
Rickets
Demineralisation of bone - soft pliable bones
Characteristic bow leg deformity
Overgrowth of the costochondral junction - rachiatic rosary
Pigeon chest deformity
Frontal bossing - (as head growth preserved over other bone growth as calcium decreases)
How does vitamin D deficiency present in adults?
Osteomalacia
Softening of bones - results in frequent fractures
What biochemical markers are indicative of a vitamin D deficiency?
Hypocalcemia
Hypophosphatemia
Increased alkaline phosphatase
What is renal osteodystrophy or CKD mineral disorder?
A complication of chronic kidney disease
Broad term that indicates biochemical and skeletal manifestations as a consequences of CKD or end stage renal disease.
These abnormalities are normally only seen in a GFR below 60mL/min.
What are the key biochemical abnormalities seen in renal osteodystrophy or CKD mineral bone disorder?
- Increased PTH
- Decreased calcium
- Increased phosphate.
What are the two main physiological factors contributing to CKD mineral bone disorder or renal osteodystrophy?
- Failure to synthesies active VD3 (calcitriol) - leads to hypocalcemia and no bone mineralisation (soft bone)
- renal failure to excrete phosphate - hyperphosphatemia binds to remaining calcium ions resulting in decreased Ca2+, leads to elevated PTH
What is the role of Fibroblast Growth Factor in Chronic Kidney disease?
Is produced in chronic kidney disease as a compensatory or safety mechanism.
Increased by 1000 fold
Increased urinary phosphate excretion (yay!!) and decreased vitamin D synthesis (bad) by suppresion of 1-alpha hydroxylase.
This leads to reduced calcium levels and elevated PTH - secondary hyperparathyroidism.
What is osteoporosis and what are its symptoms?
Increased bone fragility as more porous - more suscpetibile to fracture particularly in the wrist, hip and spine.
Presents as painless fractures, height loss and curvature of the spine (due to compression fractures
More severe form of osteopenia
What are the common causes of osteoporosis?
Hormonal related/postmenopausal
Long use of steroids (cushing syndrome)
Malabsoprtion disease
Drug related
Low BMI
What are the indications for dual energy x-ray absorptiometry (DXA scanning or bone mineral density scan)?
For those with significant risk factors
When it is uncertain if bones are fragile
To decide whether drug treatment is necessary
Is NOT used for screening purposes
What is the principle behind a bone mineral density scan?
It measures bone density and bone loss
Bone densities are often given as a T score
T score shows what a patients bone density is like in comparison to a young adult of the same gender with a peak bone mineral density.
Posititive values -0.1 and above indicate higher than normal density or normal density
Osteopenia is between -1.0 and -2.5
Osteoporosis is -2.5 or lower
What is FRAX for assessing bone health?
WHO Fracture RIsk Assessment tool
Assesses the probability of a fracture occurring in the next ten years
This considered the age of the patient, sex, BMI, previous fractures, risks factors such as alcohol, smoking, glucocorticoids to give a percentage estimate of how likely a fracture is in the next ten years.
