Endocrine control of Ca2+ and PO4- homeostasis Flashcards
What are the main physiological roles of calcium?
Bone formation and teeth Muscle contraction Nerve function Enzyme co-factor Intracellular 2nd messenger Stabilisation of membrane potentials
What are the main physiological roles of phosphate?
ATP - intracellular metabolism
Phosphorylation
Cell membrane
Buffer (acid-base)
How much of the total body calcium (1-2kg) is stored in bones, intracellular and extracellular?
Bone - 99%
Intracellular - 1%
Extracellular - 0.1%
How is calcium stored in plasma (2.5 mmol/l)?
Ionised - 45%
Bound - 55% (anions and plasma proteins)
What 3 hormones control calcium and phosphate homeostasis?
Vitamin D (Inc calcium) Parathyroid hormone (Inc calcium) Calcitonin (Dec calcium)
What tissues/organs regulate calcium and phosphate homeostasis?
Kidneys
Bone
GI tract
Parathyroid glands (4)
What cells of the parathyroid glands are responsible for synthesising and secreting parathyroid hormone (PTH)?
Chief cells
In response to low Calcium, how does PTH affect the kidneys, bone and GI tract?
Bone: Inc osteoclasts
GI: Inc Ca and Po absorption
Kidneys: Inc Vit D synthesis, Inc Ca and Po reabsorption, dec Po in PCT
In response to low calcium, PTH increases VIt D synthesis in the kidneys. How does Vit D then affects the kidneys, bone and GI tract?
Bone: Inc osteoclast
Kidneys: Inc Ca and Po
GI: Inc Ca and Po absorption
Vit D also causes dec PTH due to -ve feedback
What cells in the thyroid gland respond to hypercalcaemia?
Parafollicular cells release calcitonin, in response to high calcium levels
What effects does calcitonin have on the kidneys, bone and GI tract?
Kidneys: Dec Ca and Po reabsorption
Bone: Inhibit osteoclast action
GI: nothing!
What 2 ways does the body produce/absorb Vit D?
Skin: Produces D3 (colecalciferol) (90%)
Diet: Absorb D2 and D3 (10%)
How is Vit D synthesised from the liver?
D3 is converted to 25(OH)D - Calcidiol by alpha1hydroxylase
This is then converted to 1,25(OH)D - Calcitriol by hydroxylase
(Can be inactivated by 24 hydroxylase)
What is the mechanism by which low calcium increases PTH?
Decreased CaSR (calcium sensing receptor) signalling: Dec cAMP and dec production & secretion PTH
What is the mechanism by which high calcium decreases PTH?
Ca+CaSR activates PLC - suppression of PTH secretion and gene expression.
activation iG-protein signalling, inhibits AC, dec cAMP, inc suppression PTH production.
What is PTHrP and what does it do? (parathyroid hormone related peptide)
Mimics PTH and elevates calcium levels
can be produced by some cancers/tissues
Which part of the intestine does calcium absorption occur?
Duodenum and jejunum
How is calcium absorbed in the GI tract?
Paracellular route (Ca and CaBP) Active uptake (TRPV6) and extrusion (CaATPase) Endocytosis (TRPV6) and exocytosis of Ca/CaBP complex
How is phosphate absorbed in the intestine?
NPT2b major transporter intestine
Increased by 1,25D and low dietary PO4
Inhibited by high dietary PO4
How does calcium reabsorption occur in the distal tubule?
PTH and vitamin D up-regulate luminal Ca2+ channels (TRPV5) and basolateral Ca2+ efflux transporters.
How does PTH dec phosphate reabsorption in the Proximal convoluted tubule?
PTH increases urinary phosphate excretion by reducing NaPi-dependent phosphate uptake in the proximal tubular epithelial cells
What are the S&S of hypercalcaemia? (Bones, stones and groans)
Osteoporosis Shortened QT Polydipsia/Polyuria Muscle weakness Kidney stones
What are the S&S of hypocalcaemia?
Tetany - muscle spasms Long QT Carpopedal spasm Paraesthesia Seizures
What can cause hypercalcaemia?
Bone erosion by malignancy
Primary (1) hyperparathyroidism
