Lecture 17 Flashcards
How much calcium do we need per day?
1000 mg
Where is most of the calcium present in the body?
In the bone (99%)
What does the skeleton provide?
- structural support
- major reserve of calcium
- maintenance of serum Ca2+
- release calcium phosphate into interstitium
- uptaking calcium phosphate
How is calcium stored in the body?
50% in ionised form= active
10% complexed with something (easily accessible)
40% bound to plasma proteins (not easily moved across cell membranes)
What is the serum calcium?
2.2-2.6 mM
How do we regulates serum calcium levels?
3 hormones
- parathyroid hormone (elevate calcium)
- calcitriol (made in skin from sunlight and interaction with steroid= vitamin D3)
- calcitonin (made by C cells in thyroid gland-lower serum calcium levels ): doesn’t do much in humans
What are some roles of serum calcium?
- regulates heart rhythm
- eases insomnia
- builds and maintains bones and teeth
- regulates passage of nutrients in and out of cell walls
- assists normal blood clotting
- important to norma kidney function
- normal nerve and muscle function
- important in intracellular signalling
Why is calcium placed in EDTA tube?
Calcium is vital for blood clotting (factor 4)
EDTA is a calcium celator stopping it being biologically active= stops blood clots forming
Why do you find citrate in a blood bag?
Citrate chelates calcium
After blood transfusions need to give the patient intravenous calcium
Where do you find the parathyroid glands?
Parathyroid glands sit attached to thyroid gland (usually 4)
What does the H and E stain of parathyroid hormone look like?
- capsule around parathyroid gland
- lots of adipose tissue
- chief cells: produce parathyroid hormone
- oxyphil cells: unknown function
How does PTH travel?
No serum binding protein
pro-pre-hormone is cleaved to 84 AA’s
How is PTH synthesis responsive to changes in serum calcium?
Low serum calcium: up-regulates gene transcription and prolongs the survival of mRNA
High serum calcium: down regulates PTH synthesis
Half life of PTH?
Short- 4 1/2 mins,
Is PTH stored?
No, you make it in demand to need
Effect of PTH?
- Bone: increases resorption of calcium from bones (activation of osteoclasts)
- Increases activation of vitamin D (calcitriol) via activation of C-1-hydroxylase enzyme, and therefore an ability for the GI tract to absorb more calcium across gut
- lowers amount of calcium lost in urine (kidneys reabsorb extra calcium)
Why does PTH cause kidneys to increase the amount of phosphate they excrete?
Calcium phosphate crystals formed in urine/kidneys if high levels of calcium and phosphate, therefore they excrete phosphate to prevent crystals forming due to increase resorption of calcium.
Function of PTH on skeleton/bone:
Increasing activity of osteoclasts, decreases activity of osteoblasts
-induces osteoblasts to secrete cytokines on cell surface
-cytokines stimulate differentiation and activity in osteoclasts and protects them from apoptosis
(PTH stimulates osteolysis:destruction of bone, in 1-2 hrs)
How is vitamin D made?
- UVB from sunlight converts cholesterol to D3 (cholecalciferol)
- in liver D3 is converted to 25(OH)D
- in the kidney 25(OH)D turns into its active form:calcitriol/1,25(OH)2D where it acts primarily on gut
(Not secreted as a classical endocrine hormone)
Effect of calcitriol?
- increases calcium removal from skeleton
- calcium reabsorbed from urine and increases phosphate excretion
- increased calcium absorption from gut
- enhances effect of PTH
- longer acting than PTH
Where is calcitonin produced?
C cells in thyroid gland (C cell looks out of place around follicles)
What is the action of calcitonin?
Decrease calcium levels in blood, produced by thyroid gland
little function
What symptoms appear with hypercalcaemia?
- renal stones
- kidney damage
- constipation
- dehydration
- tiredness
- depressed
Symptoms of hypocalcaemia?
Hyperexcitability of neuromuscular junction as lower serum calcium causes more Na+ entry into neurones. -pins and needles -muscle spasms (tetany) -paralysis -convulsions (Can lead to death)
What is the serum calcium for severe hypercalcemia?
> 3 mmol/L
- leads to polyuria = dehydration (need to rehydrate)
- lethargy
- weakness
- confusion
- go into coma: once rehydrated they awaken
Why would a patient have hypercalcemia?
-malignant osteolytic bone metastasis (hole in bone- calcium liberated from bone)
What are some common cancers that metastasise to the bone?
- prostate (causes osteoblastic rather than osteolytis- does not liberate calcium)
- breast
- lung
- renal
- thyroid
Common sites for bone metastasis:
- vertebrae
- pelvis
- proximal parts of femur
- ribs
- proximal part of humerus
- skull
What is multiple myeloma in skull?
Lots of osteoclast activity secondary to another cancer, causing lots of small holes to form
What are the types of hyperparathyroidism?
Primary
-one of the parathyroid glands develops an adenoma: secretes excessive about of PTH (causes calcium to rise and phosphate to fall)
Secondary
- all 4 parathyroid glands become hyperplastic
- seen in patients with vit D deficiency: meaning calcium absorption is low resulting in low serum calcium levels causing PTH to rise
- seen in patients with chronic renal failure due to failure of the 25 hydroxylation of vit D
Symptoms of primary hyperPTH:
Stones:kidney stones and polyuria
Moans:tired/exhausted/depressed
Groans: constipation, peptic ulcers, pancreatitis
Bones: bone and muscle aches
How does calcium effect neuronal activity?
Hypercalcaemia: supression of neuronal activity (lethargy, confusion, coma)
Hypocalcaemia: excitable nerves (tingling, muscle tetany, epilepsy)
How do you get hypocalcemia?
-parathyroid gland become ischaemic/removed during surgery
Symptoms with hypocalcemia?
- tingling around mouth and fingers
- tetany of muscles
- carpopedal spasm (painful cramps in hands and feet)
Difference between osteomalacia and osteoporosis?
Porosis: in older people, channels/holes in bone but is fully mineralised
Malacia: softening but normal structure (underminerailsation due to lack of vit D)
In children called rickets: deformity/bone pain
What are some food sources of vitamin D?
Cheese, butter, margarine, fortified milk, fish, fortified cereals
How does D3 compare to other hormones?
It is not secreted by a classical endocrine gland
Is PTH or calcitriol longer acting?
Calcitriol is longer acting: long term
PTH is for short term regulation
At what calcium level does hypocalcaemia become symptomatic?
<2.1 mmol/L
What is parathyroid hormone related peptide? (PTHrP)
Produced by tumours: similar action to PTH
- increased calcium release from bone
- does not increase renal C-1 hydroxylase so doesnt increase calcitriol concentration unlike PTH
What effect does PTH have on vit D synthesis (calcitriol)?
Increases activity of C-1 hydroxylase activity which converts 25(OH)D to calcitriol
