Endocrinology Session 4 Flashcards
What cellular processes is calcium involved in?
- Hormone secretion
- Muscle contraction
- Nerve conduction
- Exocytosis
- Intracellular second messenger
How is the calcium sequestrated in bone?
Hydroxyapatite crystals (within collagen fibres)
What is the function of phosphate?
- Cellular energy metabolism (ATP)
- Levels fluctuate
How are calcium and phosphate regulated?
- Parathyroid hormone
- 1,25-dihydroxyvitamin D / calcitriol
- Calcitonin (less)
What is the function of the skeleton?
- Providing structural support
- Major reserve of calcium
- Buffering serum levels
- Releasing calcium phosphate into interstitium
- Taking up calcium phosphate
What do the 3 hormones ac on?
Bone, kidneys, GI tract
How much calcium does the adult human have?*
1000g
What are the main dietary sources of calcium?
Dairy
What is protein bound calcium used for?
- Not easily moved across cell membranes
- Not biologically active
- Serves as a reserve
How much calcium is reabsorbed in the kidneys?
About 98%
What three physiochemical forms of calcium in plasma?
1) Free ionised species (45%)
2) Bound to anionic sites on serum proteins (albumins) 45%
3) Complexed with low-molecular weight organic ions (10%)
What is the total concentration of all three forms of calcium in plasma?
2.2-2.7 mmol/L
Which plasma calcium is measured and which one is physiologically active?
- Free ionised is physiologically active
- Total calcium is commonly measured and then levels are corrected
What is hypocalcaemia and what does it result in?
Low calcium concentration
- Hyperexcitability of the nervous system (+ NMJ)
- Paraesthesia
- Tetany, paralysis, convulsions
What is chronic hypercalcaemia and what does it result in?
Elevated calcium levels over a longer period of time
- Kidney stones
- Constipations
- Dehydration
- Kidney damage
- Tiredness
- Depression
What is responsible for the short and long term control of serum calcium concentration?
- Short: parathyroid hormone
- Long: calcitriol
How is PTH synthesised?
- Pro-pre-hormone cleaved
- Regulated at the transcriptional and post transcriptional levels, so:
Low serum calcium = upregulated gene transcription, prolonged mRNA survival
High serum calcium = downregulated gene transcription
What is the half life of PTH and why?
4 1/2 minutes - means that the hormone is responding quickly
What is the function of chief cells?
Degradation and synthesis of PTH (cleavage initiated by high serum calcium levels)
What are the target organs and the physiological effects of PTH?
- Bone: increased osteoclast activation to release calcium and phosphate into blood
- Intestine: activated vit. D and increases transcellular uptake
- Kidney: decreases loss to urine (more reabsorption)
What is the relationship between calcium and phosphate?
If more phosphate is excreted, more calcium is reabsorbed which reduces the likelihood of crystal formation
How is bone deposited?
Osteoblasts producing collagen matrix mineralised by hydroxyapatite
How is bone reabsorbed?
Osteoclasts producing an acid micro-environment to dissolve hydroxyapatite
How does PTH act on the bone?
- Stimulated osteolysis
- Inducing osteoblastic cells to synthesise and secrete cytokines on cell surface
- Decreased osteoblast activity exposes bony surface to osteoclasts
What is the feedback regulation of serum calcium?*
- Increase = lower PTH secretion
- Less Ca2+ reabsorbed from gut
- Less vit D and less Ca2+ from gut
- More bone building
= Lower plasma Ca2+
What are the symptoms of chronic hypercalcaemia?
- Renal calculi
- Kidney damage
- Constipation
- Tiredness
- Depression
Stones, moans, groand
When do symptoms of severe hypercalcaemia appear?
- When serum calcium raises above 3.0 mmol/L
- Lethargy
- Weakness
- Confusion
- Coma
- Renal failure
How do you treat hypercalcaemia?
Rehydration
What is the aetiology of hypercalcaemia?
- Malignant osteolytic bone mets (big bone patches missing)
- Multiple myeloma
- Cancers that metastasise to bone (breast, lung, renal, thyroid)
Why would prostate cancer mets not cause hypercalcaemia?
Rather than osteolytic mets, it causes osteoblastic mets and no calcium will be liberated so it would not cause hypercalcaemia
What are the common sites for bone metastases?*
- Vertebra
- Pelvis
- Proximal femur
- Ribs
- Proximal humerus
- Skull
What is primary hyperparathyroidism?
A condition where one of the four parathyroid glands develops an adenoma which secretes excess PTH
- Causes serum calcium rises and phosphate falls
What is secondary hyperparathyroidism?
A condition where all 4 parathyroid glands become hyperplastic
What causes secondary hyperparathyroidism?
- Vitamin D deficiency
- Low serum calcium absorption so low calcium and therefore high PTH
What are the symptoms of primary hyperparathyroidism?
- Stones (kidney)
- Moans (tiredness, depression)
- Groans (constipation)
- Bones (+ muscle aches)
Why does hypercalcaemia lead to suppression of neuronal activity?
More is needed to fire the action potential, and therefore not as many will fire
Why does hypocalcaemia lead to excitabe nerves?
Less contribution to RMP so less needed to reach threshold and more will fire
When is symptomatic hypocalcaemia seen?
- When serum calcium falls below 2.1 mmol/l
- Most common in post-total thyroidectomy
- Can start within 6 hours of thyroidectomy
What are the symptoms of hypocalcaemia?*
- Tingling in mouth and fingers
- Tetany of muscles
- Carpopedal spasm
What is the difference between osteoporosis and osteomalacia?
- Osteomalacia: normal bone structure that is under mineralised
- Osteoporosis: structurally degraded bone that is fully mineralised
What is the cause of osteomalacia?
- Vitamin D deficiency
- Rickets in children
- Can be due to diet or renal disease
What are the symptoms of osteomalacia?*
- Bone pain
- Muscle weakness
- Deformity
How is vitamin D obtained?
Sun exposure, food, supplements
How is inert vitamin D converted into 1,25-dihydroxycalficerol?
By undergoing two hydroxylation reactions
What is parathyroid hormone related peptide?
A peptide that is produced by tumours and mimics the action of PTH without increasing calcitriol concentration
Causes humeral hypercalcaemia of malignancy (HMM)
What does PTHrP cause?
- Increased calcium release from bone
- Reduced renal calcium excretion
- Reduced renal phosphate reabsorption
= Hypercalcaemia
Why des PTHrP not increase calcitriol concentration?
- Does not increase renal C-1 hydroxylase activity that catalyses the hydroxylation of calcifediol to calcitriol
- Therefore cannot make calcitriol
- So no increase in concentration
