Calcium Flashcards
Why is it important to maintain calcium levels within set limits?
Too low -> hypocalcaemia
Too high -> hypercalcaemia
List the hormones involved in the control of calcium levels in the serum
Parathyroid hormone (PTH) - primarily
Calcitriol (1,25-dihydroxyvitamin D) - primarily
Calcitonin - lesser extent
How is the serum concentration of calcium regulated by hormones?
PTH and calcitrol both raise calcium plasma levels:
Short-term regulation - PTH
Long-term regulation - calcitriol
How does the parathyroid and vitamin D interact?
PTH stimulates the hydroxylation of Vitamin D by kidney enzymes that convert it into its active form calcitriol
How is the parathyroid hormone regulated?
Parathyroid chief cells stimulated by low levels of Ca2+ in blood to release more PTH
How is vitamin D regulated?
PTH increases synthesis of active vitamin D by stimulating its hydroxylation in the kidneys
What is the significance of renal function on calcium metabolism?
- PTH slows loss of Ca2+ from blood into urine (and increases phosphate loss)
- Calcitiol increases absorption of both Ca2+ and phosphate from the blood
Which organ systems do the calcium hormones: PTH, calcitriol and calcitonin effect?
Bone
Kidney
GI tract
How do the calcium hormones differ in their affects on Ca2+ and PO4(3-) levels?
Typically they oppose - e.g. one hormone that elevates the level of one will lower that of the other
Which cellular processes does calcium play a critical role in?
Hormone secretion Coagulation Bone formation Neuromuscular excitability Synaptic transmission Exocytosis Activation/inactivation of many enzymes Intracellular second messenger (between PM and cell interior) for hormones and growth factors Coordination of metabolic activity Regulation of gene transcription
What is the physiologically active form of the metal, calcium?
free ionised calcium Ca2+
What functions does phosphate have in the body?
Energy metabolism - ATP,GTP,AMP,ADP Protein phosphorylation - activation/deactivation enzymes Genetic information (DNA/RNA) Structure of membrane phospholipids Bone formation
Are plasma phosphate levels strictly regulated?
No - they fluctuate throughout the day, especially after meals
Why are calcium and phosphate homoeostasis intimately linked?
- They are both the principal components of hydroxyapatitie crystals (major portion of mineral phase of bone)
- Regulated by the same hormones: PTH, calcitriol, calcitonin
Describe the interplay in calcium between the GI tract and ECF
Calcium is absorbed from the GIT into the ECF and secreted from the ECF into the GIT
Describe the interplay in calcium between the bone and ECF
Calcium from the ECF is used to form bone. Calcium from bone is reabsorbed into the ECF
Describe the interplay in calcium between the kidneys and ECF
Calcium is filtered from blood in the kidneys and some is reabsorbed. The amount filtered vs reabsorbed affects the ECF calcium level
Where is the largest store of calcium in the body?
Bone - approximately 1kg
Which type of food product is the major source of dietary calcium?
Dairy products
A person is in calcium balance. Describe the interplay of Ca2+ between organ systems that you would expect
Urinary excretion of Ca2+ is the same as net absorption (absorption-secretion) by the GIT.
What would you expect bone formation and reabsorption be like in a steady state?
Calcium deposition is matched equally by calcium reabsorption
In plasma, calcium takes which three physiochemical forms?
- As a free ionised species (Ca2+) - 45%
- Associated with anionic sites on serum proteins (esp. albumin) - 45%
Complexed with low molecular weight organic anions (e.g. citrate and oxaloacetate) - 10%
What is the charge on an anion?
negative - attracted to anodes
What is the charge on a cation?
positive - attracted to cathodes
It is the free ionised calcium that is physiologically active, however common lab tests measure total calcium which include that which is bound to albumin and other proteins. How do they determine whether the amount of free calcium is in the correct range or not?
The levels are corrected depending on the level of albumin
What are the consequences of hypocalcaemia?
Hyperexitability of the NS, including neuromuscular junction, leading to:
paraesthesia - ‘pins & needles’ abnormal sensation
then tetany - intermittent muscular spasms
paralysis
and even convulsions
What may chronic hypercalcaemia results in?
"Bones, stones, groans and psychiatric overtones" Kidney stone formation (renal calculi) constipation frequent urination dehydration kidney damage lethargy nausea depression cardiac arrhythmias
What is Vitamin D?
A collective term for a group of prohormones. The two major forms are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol)
Where is Vitamin D obtained from?
sun exposure -UVB light
food
supplements
The Vitamin D obtained from food, the sun and supplements is biologically inert. How is it activated to form calcitriol?
It undergoes two hydroxylation reactions
In which two important ways does the control of plasma Ca2+ differ from that of the regulation of Na+ and K+?
- The extent of Ca2+ absorption from GIT is hormonally controlled and depends on Ca2+ status of body - (K+ and Na+ homeostasis is mainly controlled by regulating urinary excretion)
- Bone serves as a large Ca2+ reservoir that can be drawn on to maintain free plasma Ca2+ levels - (similar in-house stores not available for K+ and Na+)
What are the blood tests to test for hypercalcaemia?
- Serum calcium - venous blood sample (no anticoagulant, albumin measured at the same time)
- Alkaline phoshatase levels - raised
- PTHrp levels - if unexplained hypercalcaemia
What is bone-specific alkaline phosphatase (BAP)?
An enzyme present on the surface of osteoblasts and in plasma
What is bone-specific alkaline phosphatase (BAP) a marker for?
Marker for bone turnover - high plasma levels correlate with increased activity of osteoblasts(lay down bone) (and expression of BAP on their surface) and hence bone turnover
What are the two main mechanisms in which malignancy can cause hypercalcaemia?
- Haematological malignancies (e.g. myeloma) and those metastasize to bone (e.g. breast or prostrate cancer) produce local factors that act in a paracrine manner to ACTIVATE OSTEOCLASTS
- Squamous tumours of the lung, head and neck produce a hormone, PARATHYROID HORMONE-RELATED PEPTIDE (PTHrp) that acts at parathyroid hormone receptors
What secreted parathyroid hormone-related peptide (PTHrp)?
Some tumours cells e.g. squamous tumours of the lung or head and neck
In which ways does PTHrp mimic PTH and in which ways does it not?
Mimics: binds to PTH receptors and increase calcium release from bone and renal calcium excretion and renal phoshate reabsorption
Not mimic: PTHrp does not increase renal C-1 hydroxylase enzyme, which normally increases concentrations of calcitriol
How many parathyroid glands are there?
4
Where are the parathyroid glands located?
In the neck. Two on the posterior surface of each lobe of the thyroid gland.
Which cells produce the PTH?
Principal cells (chief cells) or the parathyroid
What is the role of PTH?
Regulates levels of Ca+ and phosphate (HPO4^2- and H2PO4^-) in the blood:
Increases plasma calcium levels
Decreases plasma phosphate levels
What type of hormone is PTH?
Peptide hormone
Which three organs does PTH target?
Bones
Kidneys
GIT (indirectly via calcitriol)
What effect does PTH have on bones?
Increases number and activity of osteoclasts
What effect does PTH have on the kidneys?
Slows rate of Ca2+ loss from blood into urine
Increases loss of phosphate from blood into urine
Why does PTH results in a decrease in blood plasma levels when PTH increases the release of phosphate from bones by stimulating osteoclast activity?
It results in a NET LOSS because more phosphate is lost from urine than gained from bones
What is the effect of PTH on the GIT (indirectly via calcitriol)?
PTH promotes the formation of calcitriol. Calcitriol increases the rate of Ca2+ and phosphate absorption from food in the GIT into the blood
Why is bone called a dynamic tissue?
Bone mass has a turnover (15% of mass a year) due to:
Osteoclast demineralisation of bone
Osteoblast laying down new bone
What are osteocytes?
“retired” osteoblasts “imprisoned” within bone they have laid down around themselves
How do osteoclasts demineralise bone?
They release acids that dissolve calcium phosphate and enzymes that break down organic matrix
PTH causes a fast and slow exchange of Ca2+ between bone and plasma. What is meant by the ‘slow exchange’?
When PTH-induces dissolution of mineralised bone (the ‘stable pool of Ca2+) and moves it into plasma
PTH causes a fast and slow exchange of Ca2+ between bone and plasma. What is meant by ‘fast exchange’?
When Ca2+ is moved into the plasma from the bone fluid (the ‘labile pool’ of Ca2+) by PTH-activated Ca2+ pumps located in the osteocytic-osteoblastic membrane
Which hormone is the most important for “minute to minute” control of calcium?
PTH
How and where do the two hydroxylation reactions that activate vitamin D occur?
- Hydroxylation by liver enzymes
2. Hydroxylation by kidney enzymes (stimulated by PTH and low plasma phosphate levels)
What type of hormone is calcitonin?
peptide hormone
Which cells produce calcitonin?
Parafollicular (C-cells) of thyroid gland
What stimulates calcitonin secretion?
- High levels of plasma Ca2+
2. Gastrointestinal hormones (e.g. gastrin)
What is the effect of calcitonin on calcium and phosphate levels?
Decreases both calcium and phosphate levels.
Minor role in humans (except maybe in childhood and during pregnancy and lactation where may serve to preserve the maternal skeleton). Very little effect on calcium homeostasis is adult levels dramatically increase or decrease.
How does calcitonin decrease blood calcium and phosphate levels?
It promotes movement of calcium and phosphate into bone matrix
What is humeral hypercalcaemia of malignancy (HMM)?
Hypercalcaemia caused by secretion of PTHrP by some cancer cells - especially breast or prostate cancer and occasionally in patients with myeloma
How can HMM be diagnosed?
High PTHrP levels
Elevated total and ionised calcium
Low PTH
No other cause for elevated calcium (exclusion of excessive Vitamin D, sarcoid, TB and other cause)
