Calcium Metabolism Flashcards
What are some of the functions of Ca
Hormone secretion
Muscle contraction
Nerve conduction
Exocytosis
Activation and inactivation of enzymes
Intracellular second messenger
Regulates heart rhythm
Builds and maintains bones and teeth
What are the hormones involved in Ca and phophate homeostasis
Parathyroid hormone
1,25-dihydroxyvitamin D (Calcitrol)
Calcitonin
In what form are calcium and phosphate stored in the bone
Hydroxyapatite crystals
Where do the hormones involved in Ca and phosphate metabolism act
Bone
Kidneys
GI tract
How does calcium exist within the plasma
Free ionized species
Bound to anionic sites on serum proteins
Complexed with low-molecular-weight organic anions
What does hypocalcaemia result in
- Hyperexcitability in nervous system - neuromuscular junction leading to:
- Paraesthesia
- Tetany
- Paralysis
- Convulsions
What does chronic hypercalcaemia result in
Kidney stones
Constipation
Dehydration
Kidney damage
Tiredness
Depression
Stones, Moans, Groans and Bones
How is synthesis of PTH regulated
High serum Ca down-regulates transcription
Low serum Ca up-regulates transcription
Low serum Ca prolongs mRNA survival
Where is Vit D obtained
Sun exposure
Food
Supplements
What is PTHrP, where is it produced and what does it do
Parathyroid hormone related peptide
It is produced by tumours and may lead to hypercalcaemia - humeral hypercalcaemia of malignancy (HHM)
What actions does PTHrP have and not have
Increases calcium release from bone
Reduces renal calcium excretion
Reduces renal phosphate reabsorption
Does not increase renal C-1 hydroxylase activity so does not increase calcitriol concentration
What cancers commonly produce PTHrP
Breast
Prostate
Where is calcitonin produced
C-cells in the thyroid gland
Where are the parathyroid galnds located
Back of the thyroid gland, usually 4
What cells are present in the parathyroid gland and what do they produce
Cheif cells - produce PTH
Oxyphil cells
What effect does calcitriol have
Increases absorption of Ca by digestive tract - via transcellular uptake and endocytosis and exocytosis of Ca-CaBP complex
Increases resorption of Ca by osteoclasts
Increases reabsorption of Ca by kidneys
What effect does PTH have
Increases resorption of Ca by osteoclasts
Increases reabsorption of Ca by kidneys
Stimulates activation of Vit A to increase uptake of Ca in gut by transcellular uptake
Describe how vitamin D is activated
Vit D is hydroxylated in the liver to 25-hydroxyvitamin D
25-hydroxyvitamin D is then transported to the kidneys where it is filtered by the glomerulus and enteres PCT where it is converted to the active form by 1a-hydroxylase
How is hydroxylation of 25-hydroxyvitmin D regualted
Negative feedback by serum Ca
Stimulated by elevated PTH
What causes hypercalcaemia
Malignant osteolytic bone metastases
Multiple myeloma
Which cancers causes malignant osteolytic bone metastases and where do they metastasise to
Breast, lung, renal and thyroid cancers
Metastasise to: vertebrae, pelvis, proximal femur, ribs, proximal humerus, skull
What are the two forms of hyperparathyroidism
Primary
Secondary
What causes primary hyperparathyroidism
One parathyroid gland develops a PTH secreting adenoma
Causes an increased serum Ca and decreased serum phosphate
What are the symptoms of primary hyperparathyroidism
Moans - tired, exhausted, depressed
Groans - constipation, peptic ulcers, pancreatitis
Stones - kidney stones, polyuria
Bones - bone and muscle aches
What causes secondary hyperparathyroidism
Parathyroid glands become hyperplastic - seen in Vit D deficiency due to dietary/environmental or chronic renal failure as Vit D not activated
Vit D deficiency means Ca absorption low so low serum Ca causing PTH to rise, this activates osteoclasts to release Ca from bone causing bone pain due to osteomalacia
What are the symptoms of severe hypercalcaemia
Dehydration
Lethargy
Weakness
Confusion
Coma
Renal failure
What is the main treatment of hypercalcaemia
Rehydration
Where is hypocalcaemia mostly seen
In post total-thyroidectomy patients
What are the symptoms of hypocalcaemia
Tingling around the mouth and in the fingers
Muscle tetany
Carpopedal spasm
Chvostek’s sign - twitching of mouth when facial nerve tapped
How does an increase or decrease in serum calcium affect on neuronal activity
Hypercalcaemia suppresses activity by raising threshold
Hypocalcaemia causes excitability by lowering threshold
What is osteoporosis
Decreased bone density with normal ratio of mineral to matrix
There is degeneration of constructed bones causing brittle bones
What is osteomalacia
Where the mineral to matrix ratio is decreased causing soft bones, prone to bending
Due to Vit D deficiency
What are the risk factors for osteoporosis
Postmenopausal women
Low BMI
Long-term oral steroid use
Heavy drinker
Smoker
Prolonged inactivity
