calcium Flashcards
Causes of hypoparathyroidism (4)
1 Most common: damage/removal of parathyroid glands
2 autoimmune disease
3 extensive cancer radiation treatment
4 low levels of magnesium: affects function of parathyroid gland - Mg dependent cyclase activity for PTH release
Define:
1 osteoarthritis
2 osteoporosis
3 rheumatoid arthritis
1 degeneration of joint cartilage and underlying bone. Most common > middle age, causes pain and stiffness, esp. hip, knee and thumb.
2 medical condition in which bones become brittle and fragile from loss of tissue. Bone density decreases due to loss of minerals e.g. Ca+, bones become thinner, less dense and break more easily. Typically as a result of hormonal changes, Vit D deficiency or Ca+ deficiency.
3 chronic inflammatory disorder that typically affects small joints in hands and feet. Autoimmune disease.
Causes of hyperparathyroidism (3)
Consequences of hyperparathyroidism (3)
1 Most common: parathyroid tumour = primary hyperparathyroidism
2 severe Ca+ deficiency due to impaired GIT absorption - secondary hyperparathyroidism
3 severe vit D deficiency - secondary hyperparathyroidism
consequences:
1 bones = soft, fragile and deformed
2 raised blood levels of Ca+ and PO4-
3 promotes formation of kidney stones composed of calcium phosphate
Multiple myeloma signs/symptoms (9)
C - hypercalcemia
R - renal impairment
A - anaemia
B - bone lytic lesions
+
1 frequent infections
2 SOB
3 epistaxis/easy bruising due to fewer platelets
4 feeling sick, dizzy or confused from hypercalcaemia
5 abnormal blood counts: disturbed bone marrow environment
Briefly outline role of osteoblasts and osteoclasts
osteoblasts: synthesize soft organic matter of bone matrix - collagen (osteoid)
- fibres harden after being encrusted with hydroxyapatite crystals
osteoclasts: facilitate mineral resorption by dissolving crystals and releasing minerals into blood
- pump H+ out with Cl-
- HCl dissolves bone minerals
Steps for producing memory and plasma B cells (4)
1 VDJ recombination ensures wide variety of naive B cells
2 naive B cells encounter Ag
3 travel to GC and undergoes somatic hypermutation to generate high affinity Ag binding sites
= clonal selection and proliferation
= affinity maturatino
4 highly specific Ag receptors. B cells undergo differentiation (long lived memory / plasma) and can migrate to distinct sites in niche groups
Multiple myeloma: site of cancer and site of DNA disturbance
Cancer in bone marrow
DNA damaged in lymph nodes. Return to bone marrow where triggers turn cells cancerous
Calcitonin hormone: cells, trigger and action
C cells in thyroid gland
released in response to increased serum Ca+
inhibit osteoclast activity and stimulate osteoblast activity
decrease Ca+ absorption in GIT
inhibit kidneys and suppress Ca+ reabsorption
Chronic myeloid leukaemia: type of abnormality causing defect? symptoms?
chromosomal translocation
Upper quadrant pain and decreased appetite/weight loss from enlarged liver and spleen
+ mild fever and night sweats due to abnormal WBC count
Hypercalcemia:
1 physiological consequence
2 what level = CNS depression + other symptoms
3 possible causes (6)
4 treatment (2)
1 excess Ca+ binds to cell surface, increases charge difference across membrane. Na+ less responsive.
- BLOCKS Na+, inhibits depolarization of nerve and muscle fibres
2 >12 mg/dL. CNS depression, emotional disturbances, muscle weakness, sluggish reflexes and sometimes cardiac arrest
3
- overactive parathyroid gland: PTH
- bone cancer: can increase osteoclast activity
- multiple myeloma: increased osteoclast activity
- Diseases, such as tuberculosis and sarcoidosis, raise blood vitamin D - dysregulated production of calcitriol by activated macrophages trapped in pulmonary alveoli and granulomatous inflammation - stimulates GIT to absorb more Ca+
- immobility
- supplementation
4
- biphosphonates inhibit osteoclast activity
- loop diuretics block Na+ and Ca+ reabsorption in thick ascending loop
What protein complex regulates osteoclast differntiation? What is OPG?
RANKL from osteoblasts binds RANK on osteoclast precursors, inducing osteoclast formation.
Osteoprotegrin disrupts RANK/RANKL signalling –> inhibits osteoclastogenesis
Role of certain proteins in bone mineralization:
1 osteocalcin
2 osteonectin
3 osteopontin
1 secreted by osteoblasts: attaches to hydroxyapatite and binds calcium to bone
2 secreted by osteoblasts: initiating mineralization, promotes mineral crystal formation
3 secreted by osteoblasts, pre-osteoblasts, osteocytes, cardiac fibroblasts and myoblasts:
synthesis stimulated by CALCITRIOL (vit D)
- high affinity for calcium and forms integral part of mineralized matrix
3 hormones regulating calcium homeostasis
1 calcitriol
2 calcitonin
3 parathyroid hormone
Parthyroid hormone: trigger and actions (3)
released in response to low serum Ca+
stimulate osteoclast activity and inhibit osteoblast activity
PTH enhances Ca+ absorption by calcitriol
PTH increased renal production of calcitriol and increases Ca+ reabsorption
Multiple myeloma and immunoglobulins
Reduced number of normal immunoglobulins = reduced efficacy of immune system
Abnormal: M proteins (monoclonal immunoglobulins) and free light chain immunoglobulins = component of immunoglobulin produced in excess and can cause renal failure
Bone composition
1/3: collagen fibres
- provide flexibility
2/3: calcium phosphate
- interacts with calcium hydroxide to form hydroxyapatite crystals
- provides strength
organic matter - osteoid: collagen, carbohydrate and protein complexes
inorganic matter: 85% hydroxyapatite and 10% calcium carbonate
Chronic myeloid leukaemia: chromosomal abnormality? treatment?
1 BCR-ABL transcript is continuously active. Produces uncontrolled tyrosin kinase activity inhibiting DNA repair and causing genomic instability
2 Gleevac: inhibits activity of tyrosin kinase
Four bone cell types
1 osteoprogenitor cells: stem cells
2 osteoblasts: bone forming cells. stress and fractures stimulate stem cells to differentiate
3 osteocytes: multiple functions
- dissolve bone matrix / deposit bone matrix
- mechanosensor cells (strain sensors) that control activity of osteoblasts and osteoclasts
4 osteoclasts (giant cells): bone dissolving cells
Key transcription factor for osteoblast differentiation
runx2
Chronic myeloid leukaemia: what is it? (2 points)
Cancer of WBC - characterized by an increased and unregulated growth of predominantly myeloid cells in the bone marrow and accumulation of these cells in the blood
Stem cell disorder in which a proliferation of immature granulocytes (neutrophils, basophils and eosinophils) unable to fight infections properly, mature granuloyctes and their precursors are found
Differentiate Rickett’s and brittle bone disease
Rickett’s - vit D deficiency
Brittle bone disease - genetic disease. Mutations in COL1A1/2 which make proteins used to assemble collagen
Hypocalcemia
1 physiological consequence
2 effect
3 level at which effects begin
4 level at which laryngospasm occurs
5 causes (5)
6 treatment
1 increased neuron excitability. Decreased charge difference across cell membrane, Na+ more responsive
2 muscle tremors, spasms or cramps
3 < 6mg/dL
4 4mg/dL - laryngospasm which can shut off air flow and cause suffocation
5
- Vit D deficiency: reduced levels of calcitriol
- Diarrhea
- Thyroid tumours: removal or damage to parathyroid
- underactive parathyroid
- pregnancy and lactation: calcium demand increases
6 IV/oral Ca+ supplements, increase Vit D supplementation
