42. Calcium Flashcards
What is the difference between osteoporosis and osteomalacia?
If in respiratory alkylosis, how does the concetration of H in the blood affect Ca?
What is the normal Ca range, and is hypo or hypercalcaemia more dangerous?
Osteomalacia = softening of bones often caused by vit D deficiency (ratio of mineral:matrix decreases b/c not as much hydroxyapeatite in them); osteoporosis = decreasing bone mass but normal ratio of mineral:matrix
1/2 Ca carried around by albumin as ionised Ca2+ with H+. If in resp alkylosis, conc of H+ drops so albumin has more space to bind Ca2+ = reduced amount of free Ca2+ in blood stream
2.2 - 2.6. Hypo b/c causes arrhythmias. Ca2+ in circulatin stabilises Na+ channels on nerve and muscle cell surfaces.
Where is most of the body’s phosphate found?
What are the extracellular and intracellular functions of
a) Ca
b) P
Where is PTH produced and in response to what?
What does PTH do?
85% in minealised in bone. (Serum P almost all ionised, organic P in structural/informational/effector molecules)
a) E_xtracellular:_ bone mineal, blood coagulation, membrane excitability. Intracellular: bone mineral
b) E_xtracellular:_ signalling. Intracellular: structural, high energy bonds, phosphorylation
Produced from parathyroid gland (about 4 on back of thyroid), IRT low Ca2+.
Acts on kidney to reabsorb Ca and on bone to reclaim Ca, and upregulates enzme in kidney leading to active vit D production
What are the 2 types of parathyroid cells?
Describe PTH processing.
Does PTH level ever drop to 0?
What happens when Ca binds to the Ca-sensing receptor (GPCR)?
Chief and oxyphil cells. Chief: more, round nucleus surrounded by small cytoplasm, produce PTH. Oxyphil: scattered groups among chief cells.
PTH (peptide hormone) prod from: preproPTH (RER) -> proPTH (golgi) -> PTH (vesicles).
No - always a little bit. Secreted more IRT serum ionised Ca2+ (free-floating in blood)
Reduces PTH secretion, increases breakdown of stored PTH, supresses transcription of PTH gene
Aside from Ca, what are some other determinants of PTH secretion?
List the actions of PTH in the
a) kidney
b) bone
c) intestine
Activated vit D (calcitriol) suppress PTH transcription. P stimulates PTH transcription. Cinacalcet activates CaSR and reduces Ca levels. CaSR activation restrains parathyroid proliferation.
a) decreases Ca excretion and increases P excretion
b) increases Ca and P resorption (b/c Ca stuck to P in bone - hydroxyapetite)
c) increases Ca and P absorption
Describe renal calcium handling in the:
a) Proximal tubule
b) LoH
c) Distal tubule
What are some other renal PTH effects?
a) 65% reabsorption, paracellular, PTH-indendant, driven by voltage gradient
b) 20% reabsorption, para/transcellular transport, voltage dependant, inhibited by loop diuretics, CaSR downregulates NaK2Cl
c) 10% reabsorption, PTH upregulates: TRPV Ca channels (target for thiazide diuretics), Ca ATPase, Na/Ca exchanger.
Down reg of NaPi transporters (reduced P reabsorption), vit D activation, proximal tubule GNG (chronic hyperPTH = increased diabetes risk), inhibits Na/H2O/bicarb resorption via effects on Na/H exchanger and Na/K ATPase
What comprises bone?
How does PTH affect osteoblasts and osteoclasts?
How do the following affect bone remodelling:
a) calcitriol
b) glucocorticoid
c) oestrogen
Collagen + hydroxyapatite (mineralisation = Ca + P + alkaline phosphatase)
Upregulation. PTH and calcitriol (activated vit D) stimulate RANKL production (RANKL is produced by osteoblasts and activates osteoclasts), and downregulate OPG (soluble receptor for RANKL that stops it binding to osteoclasts)
a) increases RANKL and gut Ca absorption
b) increases RANKL, reduces osteoblast numebrs and mineral production
c) epiphyseal closure, reduce cytokine sensitivity and inhibits bone remodelling
Vit D is not a vitamin - what is it?
How is it inactivated?
Where is the vitamin D receptor found?
How is it linked to macrophages?
A steroid hormone made from cholesterol. Made in skin and converted in liver. Regulated convertion to activated vit D in kidneys.
Hydoxylating it in a few places
Nuclear (slower effects) and membrane bound (faster effects)
Calcitriol is also synthesized by monocyte-macrophages and acts locally as a cytokine, defending the body against microbial invaders by stimulating the innate immune system
How is Ca absorbed in the gut?
What effects does vitamin D have on:
a) parathyroid
b) bone
c) phosphate absorption
d) aa uptake
Absorbed across brush border, binds to calbindin -> moves around and Ca released into interstital space -> blood
a) reduces PTH transcription
b) reduces expression of T1 collagen; increases levels of osteocalcin and RANKL, facilitates osteocyte differentiation
c) increases P absorption from gut AND increases its removal via renal excretion
d) increases: deficiency -> myopathy
What does FGF23 do?
What is rickets?
What is calcitonin?
What is PTHrP?
Secreted by osteocytes in response to elevated calcitriol, acts on the kidneys, where it decreases expression of Na/P cotransporter in PCT = decreases reabsorption and increases excretion of phosphate
Defective mineralization/calcification of bones before epiphyseal closure due to deficiency or impaired metabolism of vit D, P or Ca, potentially leading to fractures and deformity.
From thyroid C-cells, imp marker of medullary thyroid cancer.
PTH related protein. Ubiquitous in foetal life, role in lactation. If secreted by a tumour -> hypercalcemia.
Describe the relationships between Ca, PTH and vit D (and feedback loops)
Differentiate between primary, secondary and tertiary hyperparathyroidism
How would you make a 10 hyperparathyroidism diagnosis?
What is the most common cause of hypoparathyroidism? How would you treat it acutely and chronically?
Primary: absence of hypocalcemia, parathyroid adenoma, carcinoma, hyperplasia. Leads to hypercalcaemia, kidney stones, osteoporosis
Secondary: compensation for hypocalcemia
Tertiary: autonomous PTH production following chronic 20
Serum Ca and PTH, 24hr urine Ca, urine Ca creatinine excretion index etc. Then localise adenoma e.g. MIBI scan
Iatrogenic e.g. thyroidectomy -> hypocalcaemia (convulsions, tetany, arrhythmia etc.). Also caused by chronic kidney disease and vit D deficiency. Acute: IV Ca. Chronic: Activated vit D
What is familial hypocalciuric hypercalcemia (FHH)?
Inactivating mutations of the CaSR. Parathyroid can’t sense Ca so not suppresed by high Ca. CaSR in kidney not activated. PTH-Ca curve shifts right.
High serum Ca, low urine Ca, high serum Mg
