Lecture 17

Question 1

How much calcium do we need per day?

Answer 1

1000 mg

Question 2

Where is most of the calcium present in the body?

Answer 2

In the bone (99%)

Question 3

What does the skeleton provide?

Answer 3

• structural support
• major reserve of calcium
• maintenance of serum Ca2+
• release calcium phosphate into interstitium
• uptaking calcium phosphate

Question 4

How is calcium stored in the body?

Answer 4

50% in ionised form= active
10% complexed with something (easily accessible)
40% bound to plasma proteins (not easily moved across cell membranes)

Question 5

What is the serum calcium?

Answer 5

2.2-2.6 mM

Question 6

How do we regulates serum calcium levels?

Answer 6

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

Question 7

What are some roles of serum calcium?

Answer 7

• 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

Question 8

Why is calcium placed in EDTA tube?

Answer 8

Calcium is vital for blood clotting (factor 4)

EDTA is a calcium celator stopping it being biologically active= stops blood clots forming

Question 9

Why do you find citrate in a blood bag?

Answer 9

Citrate chelates calcium

After blood transfusions need to give the patient intravenous calcium

Question 10

Where do you find the parathyroid glands?

Answer 10

Parathyroid glands sit attached to thyroid gland (usually 4)

Question 11

What does the H and E stain of parathyroid hormone look like?

Answer 11

• capsule around parathyroid gland
• lots of adipose tissue
• chief cells: produce parathyroid hormone
• oxyphil cells: unknown function

Question 12

How does PTH travel?

Answer 12

No serum binding protein

pro-pre-hormone is cleaved to 84 AA’s

Question 13

How is PTH synthesis responsive to changes in serum calcium?

Answer 13

Low serum calcium: up-regulates gene transcription and prolongs the survival of mRNA
High serum calcium: down regulates PTH synthesis

Question 14

Half life of PTH?

Answer 14

Short- 4 1/2 mins,

Question 15

Is PTH stored?

Answer 15

No, you make it in demand to need

Question 16

Effect of PTH?

Answer 16

• 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)

Question 17

Why does PTH cause kidneys to increase the amount of phosphate they excrete?

Answer 17

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.

Question 18

Function of PTH on skeleton/bone:

Answer 18

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)

Question 19

How is vitamin D made?

Answer 19

• 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)

Question 20

Effect of calcitriol?

Answer 20

• 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

Question 21

Where is calcitonin produced?

Answer 21

C cells in thyroid gland (C cell looks out of place around follicles)

Question 22

What is the action of calcitonin?

Answer 22

Decrease calcium levels in blood, produced by thyroid gland

little function

Question 23

What symptoms appear with hypercalcaemia?

Answer 23

• renal stones
• kidney damage
• constipation
• dehydration
• tiredness
• depressed

Question 24

Symptoms of hypocalcaemia?

Answer 24

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)

Question 25

What is the serum calcium for severe hypercalcemia?

Answer 25

>3 mmol/L - leads to polyuria = dehydration (need to rehydrate) - lethargy - weakness - confusion - go into coma: once rehydrated they awaken

Question 26

Why would a patient have hypercalcemia?

Answer 26

-malignant osteolytic bone metastasis (hole in bone- calcium liberated from bone)

Question 27

What are some common cancers that metastasise to the bone?

Answer 27

- prostate (causes osteoblastic rather than osteolytis- does not liberate calcium) - breast - lung - renal - thyroid

Question 28

Common sites for bone metastasis:

Answer 28

- vertebrae - pelvis - proximal parts of femur - ribs - proximal part of humerus - skull

Question 29

What is multiple myeloma in skull?

Answer 29

Lots of osteoclast activity secondary to another cancer, causing lots of small holes to form

Question 30

What are the types of hyperparathyroidism?

Answer 30

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

Question 31

Symptoms of primary hyperPTH:

Answer 31

Stones:kidney stones and polyuria Moans:tired/exhausted/depressed Groans: constipation, peptic ulcers, pancreatitis Bones: bone and muscle aches

Question 32

How does calcium effect neuronal activity?

Answer 32

Hypercalcaemia: supression of neuronal activity (lethargy, confusion, coma) Hypocalcaemia: excitable nerves (tingling, muscle tetany, epilepsy)

Question 33

How do you get hypocalcemia?

Answer 33

-parathyroid gland become ischaemic/removed during surgery

Question 34

Symptoms with hypocalcemia?

Answer 34

- tingling around mouth and fingers - tetany of muscles - carpopedal spasm (painful cramps in hands and feet)

Question 35

Difference between osteomalacia and osteoporosis?

Answer 35

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

Question 36

What are some food sources of vitamin D?

Answer 36

Cheese, butter, margarine, fortified milk, fish, fortified cereals

Question 37

How does D3 compare to other hormones?

Answer 37

It is not secreted by a classical endocrine gland

Question 38

Is PTH or calcitriol longer acting?

Answer 38

Calcitriol is longer acting: long term | PTH is for short term regulation

Question 39

At what calcium level does hypocalcaemia become symptomatic?

Answer 39

<2.1 mmol/L

Question 40

What is parathyroid hormone related peptide? (PTHrP)

Answer 40

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

Question 41

What effect does PTH have on vit D synthesis (calcitriol)?

Answer 41

Increases activity of C-1 hydroxylase activity which converts 25(OH)D to calcitriol