Fractures & Dislocations - Biochemistry Flashcards
Where in the body is calcium found and how is it stored
- Bone (1kg)
- Blood (10mg/l)
a) What is the storage form of calcium in bone?
b) What is also bound in bone with calcium
a) Hydroxyapatite
b) Phosphate
When is phosphate in bone released?
When bone is broken down
Why do we measure total calcium in blood?
It is cheaper
a) What does calcium bind to in blood?
b) What part is physiologically important?
a) Proteins
b) Ionised calcium
Define adjusted calcium (Aca)
The measured total calcium value adjusted for the albumin concentration
a) Why do we use adjusted calcium?
b) When is adjusted calcium particularly important
a) It is a better reflection of the ‘ionised calcium’
b) This is of particular value in chronic disease states e.g., cancer where the decrease albumin may mask hypercalcaemia
What is the equation for adjusted calcium?
Aca = Total Ca + 0.02 (40-[Albumin])
Which two hormones play a major role in controlling blood calcium concentration?
- Parathyroid hormone
- Vitamin D
a) What is the secretion of PTH directly regulated by?
b) How is PTH detected?
a) plasma calcium
b) Detected by a calcium receptor on the surface of parathyroid cells
a) What does low plasma calcium stimulate?
b) What occurs when there is high plasma calcium?
a) Stimulates PTH release from the parathyroid gland chief cells
b) Inhibits PTH release from the parathyroid gland chief cells
What are the three main actions of PTH?
- Acts on kidneys to promote Ca reabsorption via the tubules so Ca re-enters bloodstream (rapidly) - prevents loss of Ca in urine
- Stimulates osteoclast resorption of bone, releasing Ca
- Drives 1,25(OH)2 Vit D production in kidney which results in increases Ca absorption via the gut
Describe the role of calcitonin in the control of blood calcium
- Calcitonin lowers blood calcium
- When blood calcium is low calcitonin decreases, removing the inhibitory effect on osteoclasts
- This allows PTH stimulation which increases blood Ca
Describe the role of vitamin D in regulating calcium homeostasis
- Promotes calcium absorption in the intestines
- Reabsorption of calcium by the kidney
- Mobilization of calcium from bone
Describe the importance of RANKL
- Tumour necrosis family
- Decoy receptor for OPG (osteoprotegrin)
- Regulates skeletal remodelling and immune function
- Macrophage colony-stimulating factor (MCSF) + RANKL = osteoclastogenesis
Describe the role of RANKL and OPG in controlling osetoclast production
PTH stimulates osteoblasts to produce RANKL. This stimulates osetoclasts.
Oestrogen stimulates the osteoblast to produce OPG. This inhibits RANKL and so decreases the activity of osteoclasts
a) What is hypercalcaemia?
b) What are the symptoms of hypercalcaemia?
a) Aca > 2.6 mmol/L
b)
- Renal calculi (kidney stones)
- Dehydration
- Renal failure
- Fatigue
- Constipation
- Depresson
Moans - Gi conditions e.g., abdominal pain, conspitation, nausea, peptic ulcer disease, vomiting
Stones - kidney related e.g., kidney stones, frequent urination
Groans - psychological conditions e.g., confusion, dementia, depression, memory loss
Bones - bone paina nd bone-related conditions e.g., curving os spine, loss of height, fractures
Groans -
What are the causes of hypercalcaemia?
Hyperthyroidism (1’HPT)
Hypercalcaemia of malignancy (HCM, TIH) e.g., lung, breast, haematologi cancer also iatrogenic (over prescription of Ca and vitamin D)
Minor causes
- Toxicosis
- Sarcoid (a rare condition that causes small patches of red and swollen tissue)
- Growth hormone excess
- Vit A excess
- Li
- Addison’s disease (adrenal insufficiency - occurs when your body doesn’t produce enough of certain hormones)
How is hypercalcaemia diagnosed?
- History and examination - no obvious drug causes
- Investigation - Plasma Aca > 2.65 mmol/L on TWO occasions and normal renal function
- If PTH > 1.0 pmol/L then possible hyperthyroid (primary)
Describe how hypercalcaemia of malignancy (HCM) occurs
- Many tumours produce a factor that acts like PTH but is slight different in structure to PTH - known as parathyroid hormone related protein (PTHrP)
- This molecule is more potent than PTH and leads to a more severe hypercalcaemia than PTH
- Haematologic malignancies produce cytokines, TNF and locallyproduce PTHrP
a) What is hypocalcaemia?
b) What are the symptoms of hypocalcaemia?
a) Aca < 2.2 mmol/L
b)
- Parathesia (numbness, tingling)
- Muscle spasms
- Tetany (Disorder of increased neuronal excitability)
- Seizures/Fits
- Coma
- Chvostek’s sign (twitching of facial muscles in response to tapping over the facial nerve)
- Trousseau’s sign (a carpopedal spasm induced by ischaemia through inflation of a sphygmomanometer cuff to a suprasystolic blood pressure)
- Cardiac
- Arrythmia: ECG, hypotension, failure
- Catarcats
- Extraskeletal calcification (Basal ganglia)
What are the causes of hypocalcaemia?
- Renal failure
- Hypoparathyroidism
- Vitamin D deficiency/malabsorption
- Pancreaitis/Rhabdomyolysis
- Phosphate
- Prematurity/Genetic
- Adrenal insufficiency
What are the causes of hyperthyroidism?
- Post-operative (Parathyrpid, tyroid, cancer)
- Idiopathic (unkown cause)
- Auto-immune
- Functional (MG deficiency, Ca sensor)
- Di George syndrome (Tissue aplasia/dysgenesis)
- Familial
- Infiltrative (Fe, Cu, Al, Canncer, Amyloid, Sarcoid)
- Reistance
Describe treatment options of primary hyperthyroidism
Minimally invasive surgery using local anesthesia to remove the overactive parathyroid gland or glands
Label the structure of the bone
Describe the role of articular cartilage found in bone
It reduces fricton at the joints and acts as a shock absorber at freely moveable joints
a) What cells does the peristeum contain and what do these cells differentiate into?
c) Describe the role of periosteum in bone
a) It contains osteogenic progenitor cells and these differentiate into osteoblasts (bone growth)
c) It helps protect the bone, assists in fracture repair, helps nourish the bone tissue and serves as an attatchment point for tendons and ligaments
Give the two types of bone marrow found in the medullary cavity and their role
Red marrow - produces red and white blood cells and platelets
Yellow marrow - contains fat and connective tissue and produces some white blood cells
Describe how the proportion of red marrow and yellow marrow is changed from birth to adulthood
At birth, there is only red bone marrow present and as a person grows the red marrow in many of the bones is replaced with yellow marrow
By adulthood, approximately half of the bone marrow is red
What are the two distinct functions of the bone
- Compact/cortical bone
- Cancellous/spongy/trabecular bone
a) Describe compact/corticol bone
b) What is the role of compact/corticol bone?
a) Higher proprtion of bone with few spacee. It forms the outer layer of all bones. It is organised into osteons (Haversian systems)
b) As it forms the outer layer of bones it provides support and protection to the spongy bone in the centre and resists the stresses produced by weight and movement
Describe cancellus/spongy/tubercule bone
- Low proportion of bone with a lot of space
- It does not contain true osteons and consist of lamellae arranged into irregular lattic eof thin interconnecting struts (trabeculae)
- The spaces of the trabeculae are filled with red or yellow bone marrow
a) What is the main component of the bone matrix component?
b) What are the other components?
a) Type I collagen
b) Bone proteoglycan, some non-collagenous proteins, osteocalcin, osteonectin
What are the two patterns of how collagen can be laid down
- Woven bone
- Lamellar bone
a) Describe woven bone and its role
b) Describe lamelalr bone and its role
a) An immature form with random fibre orientation. It is laid down during rapid growth and fracture repair
b) It is composed of successive layers of collagen fibres with distinct orientation. It gives very strong structure.
a) Describe the structure of ostebolasts
b) What is their principle function?
a) Plump cuboidal single nucleated cells with abundant organelles (for synthesis and secretion of protein). It forms an epitheliod layer on the bone surface
b) Bone formation
a) What are lining cells
b) Can they be reactivated?
c) What process do they have an important function in
d) What types of bone cells can they communicate with?
a) Osteoblasts which have completed phase of synthetic activity
b) Can be reactivated
c) Important function in the activation of bone remodelling
d) Can communicate with osteocytes
a) What are osteocytes
b) Describe their role of osteocytes
a) Osetbolasts engulfed in bone matrix during apposition
b) Regulate calcium homeostastsis and act as a strain gauge to monitor and record the extent of physical loading
a) Describe the structure of osteoclasts
b) What is the role of osteocalsts
a) Large multincleated cells that contains unique organelles, the ruffled border and clear zone
b) Resorption of bone
State the four zones of bone growth in length
Zone1 - Resting cartilage
Zone 2 - Proliferating cartilage
Zone 3 - Hypertrophic cartilage
Zone 4 - Calcified cartilage
Describe the four zones of bone growth in length
Zone 1 - resting cartilage
- Closest to the epihysis and made up of relatively quiescent cells
- Anchors epiphyseal growth plate to the bone of the epihysis
- High matrix: cell volume allows diffusion of nutrients which maintains chondrocytes in deeper layers
Zone 2 - proliferating cartilage
- Slighty larger chondrocytes - undergo mitosis
- Produce matrix and are responsible for longitudinal growth of the bone
Zone 3 - Hypertrophic cartilage
- Older cartilage
- Cells enlarge
- Maturation zone - Increase in size, accumulation of calcium within matrix
- Degeneration zone - deteriorate and die, Ca is released from the vesicles impregnating matrix with calcium salt
- Provisional calcification zones - no active cell growth, necessary for invasion of metaphyseal blood vessels, destruction of cartilage cells, formation of bone along walls of calcified cartilage matrix
Zone 4 - Clacified cartilage
- Only a few cells thick, composed of dead chondrocyes(surrounded by calcified matrix)
- Matrix becomes calcified, cartilages cells die, matrix begins deteriorating
Zone 5 - Ossification zone
- New bone formation is occurring
How can women be converted from an endosteal resorption to a periosteal apposition?
- By manipulating nutritional intake and exercise
- Programmed excercise
- More vitamin D
What are altercations of the RANK ligand/OPG ratio be critical in?
Altercations of the RANK ligand/OPG ratio are critical in the pathogenesis of bone diseases that result from increased bone resorption
