Calcium, phosphate and parathyroid hormone
What are the clinical features of HPTH (mainly due to hyperCa)?
Nausea and vomiting, constipation, ECG changes- short QT interval, kidney stones (too much calcium presented to kidney), bone pain, osteoporosis (calcium taken from bones to blood), psychosis, altered mental status
What are the sources of phosphate?
dairy, red meat, poultry, bread, rice, oats
What are the clinical features of hypoPTH and hypoCa?
muscles: weakness, muscle cramps Nerve function: peroral numbness and tingling, Chvostek's sign (if you tap on facial nerve in front of ear, whole side of face spasms), Trousseau's sign (blood pressure cuff put on and raise pressure, hand spasms), Tetany (whole body stiffness)
Name for high phosphate levels and how does this occur? (3)
- hyperphosphateaemia - decreased renal excretion (due to renal insufficiency), acute exogenous phosphate load (e.g. phosphate containing laxatives, enemas and intravenous phosphate), redistribution of intracellular phosphate to extracellular space (especially if there's too much muscle destruction) - causes hypocalcaemia, soft tissue calcification, calcification of arteries and heart valves
What forms calcium is in in body (NOT BONE) and calcium blood levels? (4)
- 45% free or ionised fraction and is biologically functional portion of total Ca - 45% bound to albumin in pH dependent manner (acidosis reduces this fraction, alkalosis increases) - 10% as complex with anions including phosphate and citrate - Total calcium in serum ranges between 2.18-2.62 mmol/L (needs to be maintained in narrow range)
How is phosphate stored in body?
- 80% as hydroxyapatite in bones - 20% in soft tissues in both inorganic and organic molecules
What are the 2 main types of cells in parathyroid cells?
- Chief cells- functional cells, responsible for synthesising and secreting parathyroid hormones - Oxyphil cells- no recognised physiological function
How do the parathyroid glands develop?
- Develop from endoderm of 3rd and 4th pharyngeal pouches
How is phosphate balance maintained? (systemic regulation) (2)
- Endocrine (PTH) - feedback and vitamin D- intesines, kidney, bones
What is hyperparathyroidism and what are the three types? (4)
- Hyperparathyroidism- PTH too high - primary- abnormality of parathyroid gland itself- can happen in adenoma, hyperplasia, rarely carcinoma - secondary- compensatory over secretion- can happen in chronic kidney disease, vitamin deficiency (e.g. D), malabsorption - Tertiary- after SHPT is treated ( very rare) keep secreting excess PTH
How does PTH have an indirect effect on the small intestine? (2)
- Increase in active vitamin D due to its action on kidneys - vitamin D increases absorption of calcium and phosphate from intestines
How does PTH act on the kidneys?
- Increases Ca reabsorption - decreases phosphate reabsorption - increases activation of vitamin D
What are the main sources of calcium?
- Milk, cheese and other dairy foods - green leafy vegetables e.g. broccoli, cabbage and okra but not spinach
What is the function of phosphate in bones and the physiological functions?
- Skeletal integrity, primary reserve (acts as reservoir) - Intracellular processes incl nucleic acid synthesis, ATP production (provides energy at cellular level), kinase and phosphatase activity
What is the name for low phosphate levels and how does this occur? What does it cause? (3)
- hypophosphataemia - decreased intestinal absorption, increased renal wasting, redistribution from ECF into cells (common when high energy food given after starvation, causes refeeding syndrome as phosphate levels go down when it enters cells) - causes poor growth in children, fatigue, weakness, loss of appetite, bone pain and fragile bones
What is Hypoparathyroidism and what are the main causes?
- low PTH so low Ca - surgical removal or damage, autoimmune disorders
Where is calcium stored? (2)
- most of (99%) of body calcium stored in bones as hydroxyapatite (bone mineral), skeletal strength - 1% in blood, extracellular fluid and soft tissues
What is the blood level range of phosphate?
0.8-1.5mmol/L
What happens when blood calcium concentration increases?
1) Calcitonin release- high concentrations of calcium stimulate parafollicular cells in the thyroid to release calcitonin 2) Effects of calcitonin on bone- stimulates osteoblasts, inhibits osteoclasts, calcium is removed from blood and used to build bone
What happens when blood calcium concentration drops?
1) Release of parathyroid hormone from chief cells of parathyroid gland 2) a) effects of PTH on bone- inhibits osteoblasts, stimulates osteoclasts, bone is broken down releasing calcium ions into the bloodstream b) effects of pth on kidneys- PTH stimulates kidney tubule cells to recover waste calcium from the urine. PTH stimulates kidney tubule cells to release calcitriol c) Effects of calcitonin on intestine- stimulates intestines to absorb calcium from digesting food 3) Blood calcium levels increase
How does PTH act on bones?
1. inhibits osteoblasts 2. stimulate RANK ligand system 3. stimulate osteoclasts 4. resorption of bones 5. release of Ca
What is the adult daily requirement of phosphorus?
550mg/day
What are the physiological functions of calcium (8)
Cell division, cell adhesion, plasma membrane integrity, protein secretion, glycogen metabolism, muscle contraction, neuronal excitability, blood coagulation
What is the daily requirement of Ca in infants and children, teenage girls and boys and adult men and women?
Infants and children- 350-550mg/day Teenage girls and boys- 800-1000mg/day Adult men and women- 700mg/day
What is the process of production of PTH and number of amino acids at each stage?
Parathyroid hormone first produced as pre-pro-PTH (115 amino acids)-> cleaved Pro- PTH (90 amino acids)-> cleaved Active PTH (84)
What is pseudohypoparathyroidism?
Target organ resistance to PTH- developmental disorder
Are parathyroid glands functional during gestation?
Yes, to control Ca balance in foetus
