The parathyroid gland (calcium and phosphate regulation)

Question 1

Adult human contains around ……… of calcium

Answer 1

1000g

Question 2

99% of calcium is sequestered in

Answer 2

bones as hydroxyapatite crystals (Ca10(PO4)6(OH)2)

Question 3

how much calcium is exchanged between bone and ECF each day

Answer 3

300-600 mg

Question 4

skeleton provides

Answer 4

• Structural support
• Major reserve of calcium
• Helps to buffer serum levels
• Releasing calcium phosphate into interstitium
• Up taking calcium phosphate

Question 6

serum calcium

Answer 6

2.2-2.6 mH

Question 7

calcium is distributed between three itner convertible fractions

Answer 7

• Mostly ionised calcium
• Protein bound calcium
• Complexed calcium (pi, citrate etc)

Question 8

role of calcium

Answer 8

• Builds and maintains bones and teeth
• Heart rhythm
• Eases calcium
• Assists normal blood clotting
• Normal nerve function
• Normal kidney function
• Lowers BP
• Activity of some enzymes
• Intracellular signalling
• Nervous transmission at NMJ

Question 9

calcium and clotting

Answer 9

Calcium is an important clotting factor – Factor IV

Question 10

what is used in blood tests to stop blood clotting

Answer 10

EDTA- calcium chelator –> stops the blood clotting

Question 11

what is used to chelate calcium in donor blood

Answer 11

citrate

• Citrate levels may become high in patients blood
• Will need to give recipients of massive blood transfusions intravenous calcium

Question 12

which hromones regulate calcium and phosphate

Answer 12

parathryoid hormone (PTH)

calcitriol

calcitonin

Question 13

Parathyroid hormone (PTH)

Answer 13

produced and released by the parathyroid gland

• secretes in response to low plasma calcium
• affects bone, intestines and kidney

Question 14

calcitriol

Answer 14

released by the kidney from vitamin D

• increases plasma calcium

Question 15

calcitonin

Answer 15

released from the thryoid parafollicular cells

• decreases plasma calcium and phosphate
• minor role

Question 16

the parathryoid

Answer 16

4 sit on the thyroid

• Unique appearance
• Doesn’t look like a normal gland
• Capsule around parathyroid gland
• 2 cell types
  
  • Chief cells- produce parathyroid
  • Oxyphil- not sure what they do (maybe old chief cell)

Question 17

the parathryoid can be accidentally

Answer 17

Removed during thyroid surgery

• Important to try and preserve - regularly monitor serum calcium

Question 18

PTH synthesis

Answer 18

• Synthesis regulated both by transcriptional and post transcriptional levels
• Low serum calcium unregulated gene transcription
• Low serum calcium prolongs survival of mRNA
• High serum calcium down regulates

Question 19

features of PTH synthesis

Answer 19

• No serum binding protein
• Straight chain polypeptide hormone - preprohormone (115AA long), cleaved to 84AA

Question 20

PTH continually syntheses but little stored

Answer 20

• Chief cells degrade hormone as well as synthesis it
• Cleavage of PTH in chief cell accelerated by high serum calcium levels

Question 21

PTH affect on bones

Answer 21

Activates osteoclasts- calcium and phosphate released into the blood

Question 22

PTH affect on intestines

Answer 22

• Activates Vitamin D to become calcitriol and hence increases trans cellular uptake from GI tract
• GI tract can absorb more calcium

Question 23

PTH and the kidney

Answer 23

• increases reabsorption of calcium
• PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine.

*However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone*

Question 24

kidney stones

Answer 24

Calcium + Phosphate forms hydroxyapatite crystals which causes stonesà don’t want to have a peak of calcium and phosphate at the same time- therefore body has adapted to increase calcium (reabsorption), and increase phosphate excretion. Whilst PTH causes phosphate to be released from bone and increased absorption in the intestines, there is a net loss of PO4 as the loss in urine will always be greater than that gained from bones.

Question 25

bone deposition is mediated by

Answer 25

0steoblasts which produce collagen and matrix which is mineralised to hydroxyapatite

Question 26

bone reabsorption is mediated by

Answer 26

osteoclasts - produced acid micro-environment dissolving hydroxyapaptite releasing calcium and phosphate into the blood (PTH stimulates osteoclasts)

Question 27

PTH has a quick action on the bone

Answer 27

* 1-2 hrs PTH stimulates osteolysis * PTH induces osteoblastic cells to synthesis and secrete cytokines on cell surface * Cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis * PTH decreases osteoblasts activity exposing bone surface to osteoclast * Reabsorption of mineralised bone and release of Pi and Ca2+ onto extracellular fluid

Question 28

Calcitriol (1,25(OH)2D) physiological role

Answer 28

Release of calcium from bone by enhancing actions of PTH Absorption of calcium in intestine via vitamin D Increase reabsorption of ca2+ and phosphate

Question 29

calcitriole is the active form of

Answer 29

vitamin D normally produced in the kidney

Question 30

the body makes vitamien D when it is exposed to sun (acts like a hormone)

Question 31

which foods are fortified with vitamin D

Answer 31

Cheese, butter, margarine, fortified milk, fish and fortified cereals are food sources of vitamin D

Question 32

synthesis of calcitriol

Answer 32

1. Sun stimulates the production of Vitamin D3 in the skin 2. Vitamin D3 is converted to 25(OH)D (pre-hormone substrate) in the liver 3. 25(OH)D is converted to 1,25(OH)2D (Calcitriol) in the kidney under influence of PTH

Question 33

physiological action of calcitonin: bone

Answer 33

decreased reabsorption of bone

Question 34

physiological action of calcitonin: kidney

Answer 34

decreased reabsorption of calcium and phosphate

Question 35

physiological action of calcitonin: GI

Answer 35

no affect

Question 36

increased plasma calxcium

Answer 36

decrease PTH secretion

Question 37

decrease in plasma calcium

Answer 37

increase PTH secretion

Question 38

symptoms of chronic hypercalcaemia

Answer 38

Stones (hydroxyapatite) Moans (depression) Groans (abdominal pains) Bones (muscle ache) Tiredness Dehydration Constipation

Question 39

severe hypercalcaemia (\>3mmol/L) symptoms

Answer 39

* Polyuria can lead to dehydration which then exacerbates the hypercalcaemia * Lethargy * Weakness * Confusion * Coma * Renal failure * Rehydration mainstay treatment * In patients with a ligand hypercalcemia and come this is not necessarily terminal event. After rehydration many can turn home

Question 40

cancer and hypercalcaemia

Answer 40

* Malignant osteolytic bone metastasis * Multiple myeloma * Common cancers that metastasize to bone causing lytic lesions and hypercalcemia * Breast * Lung * Renal * Thyroid

Question 41

cancer and hyper/hypocalcaemia

Answer 41

Hypercalcaemia is commonly associated with cancer which is usually advanced and portends a poor prognosis. Hypocalcaemia is more often seen as a complication of therapy aimed at reducing skeletal morbidity rather than an effect of the cancer itself

Question 42

hypocalcaemia

Answer 42

Hypocalcaemia causes hyper-excitability of the neuromuscular junction.

Question 43

symptoms of hypocalcaemia

Answer 43

Symptoms include pins and needles, tetany, paralysis, and convulsions.

Question 44

common sites for bone metastasis

Answer 44

Vertebrae Pelvis Proximal parts of the femur Ribs Proximal part of the jumerus Skull More than 90% found in this distribution

Question 45

lytic lesions causes by metastsies can cause

Answer 45

hypercalcaemia