Calcium Disorders Flashcards
Distribution of calcium in the body
-dietary calcium intake =25mmol/day
Functions of calcium
-Nervous system:
Release for neurotransmitters
-Muscles:
Initiation of muscle contractions
Structural: bone, teeth
-Hormonal:
Intracellular second messenger
-Enzymatic function:
Coenzyme for coagulation factors (transfusion science)
-Cell adhesion
Cadherins:cells used for attachment,calcium binds to ir providing rigidity
Role of calcium in muscle contraction
-action potential comes through the nerves leading the release of acetylcholine,this then activates sarcoplasmic reticulum and leads to the release of calcium ions
-troponin and tropomyosin prevent the interaction between actin and myosin
-when calcium bunds to troponin it causes a conformational change=myosin binding site on actin becomes exposed so muscle contractions can occur
Calcium imaging
-confocal images used to show the activating calcium wave
-without the influx of calcium ions there is no lighter regions
3 forms of calcium
-free ionised=47%=the physiologically active,regulated by homeostatic mechanisms
-protein bound to proteins primarily like albumin=46%
-complexed calcium(in complexes with eg citrates and phosphates)=7%
3 forms of calcium
-free ionised=47%=the physiologically active,regulated by homeostatic mechanisms
-protein bound to proteins primarily like albumin=46%
-complexed calcium(in complexes with eg citrates and phosphates)=7%
Raference range of calcium
• Total calcium: 2.20-2.60 mmol/L
• Ionised calcium: 1.20-1.37 mmol/L
• Total calcium: 2.20-2.60 mmol/L
• Ionised calcium: 1.20-1.37 mmol/L
- Changes in plasma protein (albumin) concentration(total calcium 2.2-2.6mmol/l
- Changes in anion concentration
- Acidbaseabnormalities
Affected by ionised calcium 1.2-1.37
Relationship between plasma Protein concentration and calcium ion levels
-when there is high albumin levels it attracts more positive ions such as calcium as albumin is negative.
-free ionised calcium concentration levels are not affected as that’s regulated by mechanisms
-during High albumin levels the individual can experience severe dehydration and infections
-during low albumin less calcium binds to albumin.Individuals may have malnutrition,liver disease,nephrotic syndrome
-If the albumin concentration in the blood changes, so will the total calcium concentration, but not the free ionised Ca2+
What happens if albumin levels are changed
-Changes in [albumin] affect total calcium but not [Ca2+]
-Correction factor is applied to get corrected [calcium]
-If [albumin] < 40 g/L:
Corrected [calcium] = measured total [calcium] + 0.02 (40-[albumin])
If [albumin] > 45 g/L:
corrected [calcium] = measured total [calcium] - 0.02 ([albumin]-45)
Alternative: measure ionised plasma [Ca2+] directly
How do changes in anion concentration affect calcium levels
-when there are High levels of phosphate more complexes between calcium and phosphate for,lowering levels of ionised calcium ions.Individuals have Hyperphosphatemia: Decreased ionised Ca2+ and may experience Vitamin D intoxication ,Renal failure,Hypoparathyroidism
-when there are low levels of phosphate calcium detaches from the complexes increasing the concentration of ionised calcium ions.Individuals have Hypophosphatemia: Increased ionised Ca2+ and causes include Vitamin D deficiency, Diuretic therapy
-Changes in anion concentration alter the ionized Ca2+ concentration by changing the fraction of Ca2+ complexed with anions
How do changes in ph(the acid-base imbalance) affect the concentration of calcium
During alkalosis there is lower amount of h+ ions which bind to albumin allowing for more ca2+ ions to bind reducing the amount of free ionised calcium ions
During acidosis there is a higher concentration of h+ available to bind to albumin so there is higher concentration of free. Ionised calcium ions as they are not binding to albumin
If the pH changes, the free ionised [Ca2+] changes, but total calcium stays normal
What 3 hormones help to regulate homeostasis
Parathyroid hormone (PTH)
• Calcitriol also called
1,25-dihydroxycholecalciferol or 1,25-DHCC or 1,25-dihydroxyvitamin D3
• Calcitonin
PTH(parathyroid hormone)
-produced in the parathyroid glands
-to be able to perform its function it needs to be synthesised
-process of synthesis of pth:
1)pre-pro-pth which consists of 115 aa get synthesised into pro pth in the rough endoplasmic reticulum
2)pro pth which consist of 90 aa gets processed into pth(84aa)in the Golgi apparatus
3)pth has an n terminal which is biologically active ans a c terminal.PTH packages itself into parathyroid granules until its secreted
4) magnesium regulates the fusion of secretory granules=highly dependent
Action of parathyroid hormone
-Role of pth is calcium reabsorption when blood plasma calcium levels are low.Negative feedback loop
-in the bone it increases bone reabsorption via the action of osteoclast activation
-in the kidney it causes:
+increased renal calcium reabsorption
+decreased phosphate reabsorption(less complexes can form)
+decreased renal bicarbonate reabsorption
+stimulate calcitriol synthesis
-In the intestine :
• PTH indirectly increases calcium absorption from the intestine (by stimulating the production of calcitriol)
Calcitriol
• Vitamin D derivative
• Diet: Cholecalciferol
• Skin: Cholecalciferol
• Liver: 25-hydroxycholecalciferol
• Kidneys: 1,25 dihydroxycholecalciferol 24,25-dihydroxycholecalciferol (inactive)
-secretion caused by increased levels of pth,low calcium levls and low phosphate levels
Synthesis of calcitriol
-synthesis starts either due to
A)the sun which causes 7-dehydrocholesterol (provitamin D) in the skin to be converted into pre vitamin d3 and then converted into Cholecalciferol (vitamin D3) which then gets converted by the enzyme 25 hydroyxlase in the liver which then gets converted into 25-hydroxycholecaliferol and in the kidney gets converted by 1 hydroxylasee to form 1,25-dihydroxycholecalciferol (calcitriol)
B)caused by dietary intake in which vitamin d gets converted by 25 hydroxylase to 25-hydroxycholecalciferol and then gets converted in the kidney by 1 hydroxylase to form calcitriol
C)action of pth and low levels of phosphate and calcium cause the conversion of 25-hydroxycholecalciferol into calcitriol by 1 hydroxylase
If calcitriol is no longer needed 25-hydroxycholecalcifero gets converted by 24 hydroxylase to 24,25,Dhcc which is the inactive version
Functions of calcitriol
Increase calcium absorption in gut
• Increase phosphate absorption in gut
• Increase renal tubular reabsorption of Calcium • Increase bone resorption (osteoclasts)
• Inhibits calcitonin
-in the small small intestine calcitriol binds to its reception which results in calcium binding protein, increased calcium transport into blood and incarcerated intestinal absorption of phosphate
Disorders of calcium homeostasis
High plasma calcium concentration above reference range
– Hypercalcaemia
Low plasma calcium concentration below reference range
– Hypocalcaemia
Hypercalcemia
-increased GIT absorption caused by :
• Excessive Vitamin D intake
• Tuberculosis (granuloma)
• Acromegaly (1-hydroxylase activity in kidneys)
• Idiopathic hypercalcaemia of infancy (increased sensitivity to vitamin D)
-decreased renal excretion caused by:
• Thiazide diuretics (increased Ca reabsorption)
• Milk-alkali syndrome
-increased bone loss caused by:
• Malignancy
• Primary hyperparathyroidism (overactive Parathyroid gland)
• Hyperthyroidism (increased osteoclast activity)
• Familial hypocalciuric hypercalcaemia (gene
mutation in Ca sensing receptors)
Common causes of hypercalceamia
Malignant tumours away from parathyroid glands can
• produce parathyroid hormone related protein (PTHrP)(mimics pth causing increased ca2+absorption in GIT)
• Direct bone resorption, releasing Ca2+
• Tumours activating osteoclasts and bone breakdown via
prostaglandins
• Increase calcium reabsorption in kidneys
• Breast and types of lung cancer
Clinical symptoms of hypercalceamia
• Abdominal pain / constipation
• Lethargy, confusion and depression
• Nausea and vomiting
• Thirst and polyuria
• Peptic ulceration
• Muscle weakness
• Cardiac arrhythmias and cardiac arrest
• Renal damage, renal stones
• Long-standing condition – demineralization of bones
Hypercalcaemia – Investigation
Tests include:
• Plasma [calcium]
• Plasma [albumin]
• Plasma [PTH]
• Plasma [phosphate]
Determine corrected calcium
-Bigger then 2.6=measure pth is pth is low or undetectable it can indicate malignancy or some rare cause of hypercalcemia,if pth is high it indicates a primary hyperparathyroidism
-if corrected calcium is bigger or equal to 3.5 emergency action needed steps remain the Same
Management of hypercalceamia
• Treat underlying cause wherever possible
• Intravenous administration of saline in dehydrated patients
• Drugs that inhibit
• renal reabsorption of calcium • bone resorption
• Dialysis
• Emergency parathyroidectomy in very severe cases
Hypocalcemia
- decreased GIT absorption caused by vitamin d deficiency
-Increased renal excretion caused by renal Failure
-decreased bone loss caused by • Hypoparathyroidism
• Pseudohypoparathyroidism
• Magnesium deficiency
Increase ca2+ deposition:
• Rhabdomyolysis
• Acute pancreatitis
• Hungry bone syndrome
Hypocalcaemia – Clinical symptoms
• Petechiae
• Paraesthesiae (“pins and needles)
• Convulsions
• Tetany due to increased neuromuscular activity • Cardiac arrhythmias
• Bronchial spasms
• Laryngeal spasm
• Behavioural disturbances, depression
• Memory loss
• Hallucinations
• Anxiety
• Cataracts
Hypocalcemia a
management
• Treat underlying cause wherever possible
• Oral calcium supplements prescribed in mild cases
• 1,25-DHCC and precursors prescribed in vitamin D deficiency • Magnesium supplements
Hypocalcaemia – Investigation
Tests include
• Plasma [calcium]
• Plasma [albumin]
• Plasma [PTH]
• Plasma [urea]/[creatinine]
• Plasma [magnesium]
• Plasma [vitamin D]
Do the diagram
