Ca2+ homeostasis Flashcards
what is the** function **of calcium phosphate salts in the bone?
- provide structural integrity
what are examples of **important biological processes **in which Ca2+ ions are essential for?
- neuromuscular excitability
- hormonal secretion
- cell signalling
- blood coagulation
what important processes are phosphate ions essential for?
signal transduction
what can occur if the the plasma Ca2+ concentration is too low (ie hypocalcemia)?
- if there is less Ca2+ in the plasma, the membrane will become more permeable to Na+
- nerves and muscles will become** over excited **
- involuntayr muscle spasms - ie tetany
what can occur if the Ca2+ concentration in the plasma is too high (ie hypercalcemia)?
symptoms ..
- if there is too much Ca2+ in the plasma, there will be decreased neuromuscular excitability
- constipation
- fatigue
- bone pain
- kidney stones
- cardiac arrthymias
what % of total body Ca2+ is mineralised (ie not biologically available) vs the % that IS biologically available?
- 99% is mineralised
- 1% is available - freely ionised and exchangeable with ECF/plasma
what can Ca2+ be bound to in plasma?
- proteins - esp albumin
- CaPO4 - calcium phosphate
- Ca citrate (calcium salt of citric acid)
where is intracellular Ca2+ found?
smooth ER or mitochondria
what is osteoclastic resportion?
Osteoclasts break down the bone and release minerals ie Ca2+ from the tissue into the blood
Describe the composition of bone
- contains hydroxypatite crystal
- organic matrix - collagen and other proteins
what does the mineralised CAPO4 serve as in bone?
a reservoir for Ca2+ storage
what is the function of osteoblasts?
- bone formation
- bone forming cells that secrete bone matrix on which CAPO4 precipitates
- they mature enclosed in the bone matrix and become osteocytes
what is the** function of osteoclasts**?
bone resorption
* large multinucleated cells derived from monocytes whose function is to break down (resorb) bone
what 3 main hormones regulate Ca2+ and PO4 levels?
- parathyroid hormone - PTH
- 1,25- dihydroxy Vitamin 3 (calcitriol)
- calcitonin
what **3 parts of the body **do these hormones regulate Ca2+/PO4?
resportion/absorption/excretion
- bone - osteocytic osteolysis and osteoclastic resorption
- intestine
- kidneys
what is osteocytic osteolysis?
- osteoclasts can remove and remodel small amounts of their surrounding bone matrix through osteocytic osteolysis
- dosent require a decrease in bone mass
what is** bone resorption?**
- bone resorption is the breakdown of bone tissue by osteoclasts
- this results in the release of minerals - ie Ca2+ and PO4 which transfer into the plasma
- stimulated by PTH
what cells in the parathyroid gland are responsible for secreting PTH?
chief / principal cells
what are the 2 types of PTH receptor and where are they located?
- type 1 receptor - kidney and bone
- type 2 - CNS
what is the PTH related peptide protein?
- a protein member of the parathyroid hormone family that is secreted mainly by cancer tumor cells
- has PTH like actions
also secreted by oxyphil cells in the parathyroid gland
what** stimulates the release** of PTH ?
hypocalcemia (ie when plasma Ca2+ levels are low)
at what measurement does max PTH secretion occur?
units - mg/dL
below 3.5mg/dL
What are the calcium sensing receptors?
& what happens if Ca2+ levels are low/high
- G protein coupled receptors found on chief cells and other calcium sensitive cells
- in conditions when Ca2+ levels are low - less will be bound to receptor and PTH will be secreted
- when Ca2+ levels are high, more will be bound to receptor and PTH secretion will be inhibited
what is the physiological role of PTH?
- prevent/reverse hypocalcemia by **increasing free plasma Ca2+ levels **
What effect does PTH have on the bone, kidney and intestine?
-
PTH acts directly on the bone and **increases bone resorption - Ca2+ release
2. PTH acts directly on kidney **(distal tubule) and increases Ca2+ reabsorption but decreases PO4 reabsorption - PTH acts** indirectly on the intestine** by stimulating calcitonin synthesis in the kidney
what receptor are low Ca2+ levels sensed by on the renal epithelium & what happens when it is stimulated?
CaSR
* once this receptor is stimulated, Ca2+ channels are stimulated which enhances reabsorption (into blood)
how does PTH inhibit PO4 reabsorption in the kidney?
inhibits the **Na Pi channel (NPT2) **and therefore reduces PO4 reabsorption
what 2 sources is vitamin D derived from?
- photodependent production in keratincytes
- ingested in the diet
what protein is Vit D bound to in blood?
Vit D binding protein
what function does vit D have in maintaining Ca2+ homeostasis?
promoting intestinal Ca2+ absorption
what** chemical is converted to vit D** in keratinocytes?
- 7-dehydrocholesterol
in the process of vit D synthesis, **where **does the 2nd hydroxylation reaction take place and what is produced as a result?
- second reaction takes place in the kidney, catalysed by 1 alpha hydroxylase
- this reaction produces 1,25(OH)2 D3
what stimulates / promotes 1 alpha hydroylase activity?
- increase PTH
- prolactin increase
- hypophosphetemia
what high affinity protein is Ca2+ bound to in enterocytes?
calbindin 9k
what is the role of calbindin 9k?
- lowers free intracellular Ca2+
- maintains favoravle gradient of Ca2+ across apical membrane
what is calcetonin?
- produced by thyroid C cells - parafollicular cells
- plays a minor role in Ca2+ homeostasis
what is the physiological role of calcitonin?
ie in the bone/kidney/intestine
- inhibits osteoclastic activity in bone
- inhibits Ca2+ reabsorption in kidney
- inhibits Ca2+ absorption in intestine
the net effect is to reduce plasma Ca2+ levels
what is a major stimulus for calcitonin secretion?
an increase in Ca2+ plasma levels
what are the 2 main causes of primary hyperparathyroidism?
- single parathyroid adenoma
- hyperplasia - enlargement of gland
what is the clinical presentation of primary hyperparathyroidism?
- can be assymptomatic
- elevated Ca2+ levels on routine labs
- elevated PTH
- possible history of kidney stones, unexpected fractures
what is the alkaline phosphatase test used for?
this test is a marker of bone turnover
what can secondary hypoparathyroidism be caused by?
another disease that is causing lowered Ca2+ levels in blood, along with a fall in PTH
what are the possible causes of primary hypoparathyroidism?
- trauma during thyroidectomy
- polyendocrine autoimmune disorder
- Digeorge syndrome - paratyroid glands dont form properly
what are examples of symptoms of hypoparathyroidism?
- fatigue
- psychological disturbances - mood swings, anxiety
- tetany
- low Ca+
- low or absent PTH
is vitamin D considered a hormone?
yes - it has a key role in Ca2+ homeostasis
when vitamin D is synthesised, where does it travel to and what does it get converted to?
vitamin D undergoes a conversion in the liver and gets converted to its active form - calcitoriol or 1,25-(OH)2-D3
what is calbindin 9k?
a high affinity Ca2+ binding protein found in tissues like the intestine and kidney
