Musculoskeletal 001745 Flashcards
(104 cards)
1
Q
What are the 3 types of bone cell?
A
Osteoclasts
Osteoblasts
Osteocytes.
2
Q
What are osteoclasts?
A
Formed from haemopoietic cells
Break down bone tissue by releasing HCl, Cathepsin K and proteases
Important in development, growth and healing of bones
Involved in regulating concentration of mineral ions in blood
Type of macrophage.
3
Q
What are osteoblasts?
A
Formed from osteoprogenitor cells
Lay down new bone tissue - by secreting collagen and calcium with other mineral salts
Strengthen bone by crystallising on it.
4
Q
What are Osteocyte?
A
Formed from osteoblasts - which change their character when in deep bone and mature into osteocytes
Main cells of bone
Communicate via fine processes through canaliculi
Directly mineralise
Signal to osteoclasts for damage repair
Calcium homeostasis.
5
Q
What is the normal level of calcium ions in the body?
A
2.2-2.6mmol/L in plasma
6
Q
Explain Calcium Homeostasis
A
Exchange between extracellular fluid and bone to fine tune plasma concentration of calcium
Under hormonal control
7
Q
What is Ca balance
A
Long term maintenance of total calcium stores by balancing absorption and excretion of ions
8
Q
Calcium stores in body
A
Mostly as hydroxyapatite (Ca3(PO4)2) as mineralised bone and some in bone fluid which is an exchangeable pool which can release calcium ions into ECF without demineralisation of bone
9
Q
Hormones involved in calcium homeostasis
A
Parathyroid hormone
Vitamin D
Calcitonin
nothing else
10
Q
Role of calcium in body
A
Wound healing Muscle contraction Blood clotting Neurotransmitter release Intracellular signalling Maintenance of cell tight junctions Hormone release from glands enzyme activation
11
Q
Where is parathyroid hormone produced
A
Produced by chief cells in parathyroid gland
12
Q
What is PTH released in response to and where does it act?
A
Produced in response to low calcium levels in plasma and acts on kidneys, bone and GI tract to increase calcium levels
13
Q
What does PTH do to kidneys?
A
Causes kidneys to increase reabsorption of calcium ions and stimulates production of active vitamin D which acts on the GI tract to increase calcium absorption
14
Q
What does PTH do to bone?
A
Binds to receptors on osteoblasts causing production of Rank L which binds to osteoclasts and causes them to split hydroxyapatite into calcium and phosphate so calcium is released into the blood
15
Q
PTH role in phosphate concentration
A
To prevent the excess phosphates from recombining with calcium ions to form hydroxyapatite PTH causes the kidney to increase excretion of phosphates
16
Q
How is vitamin D made?
A
From 7 dehydrocholesterol in skin keratinocytes exposed to UVB - sunlight, which forms calcidiol. Calcidiol is converted to calcitriol - active vitamin D in the kidney by 1 alpha dehydrogenase
17
Q
What does Vitamin D do to calcium plasma levels?
A
Increases them
18
Q
How does Vitamin D increase calcium levels?
A
Increases reabsorption of calcium and phosphate in kidney and GI tract
Increases absorption of calcium in GI tract
Stimulates osteoclasts to break down bone to release calcium
19
Q
What does calcitonin do?
A
Decreases calcium levels of plasma
20
Q
How does calcitonin work?
A
Increases activity of osteoblasts - increases calcium deposition at bone and inhibits osteoclasts
Increases reabsorption of phosphate ions at kidney
Decreases reabsorption of calcium ions at kidney
21
Q
What is hypercalcaemia?
A
Raised levels of calcium - above 2.6mmol/L in blood serum
22
Q
Causes of hypercalcaemia
A
Malignancy - secondary bone melanoma
Hyperparathyroidism
23
Q
Symptoms of hypercalcaemia
A
Kidney stones Headache Fatigue muscle pain nausea/ vomiting - moans coma confusion drowsiness irregular heart beat bone symptoms - pain and weakness depression -groans
24
Q
What is hypocalcaemia?
A
Low blood calcium levels - below 2.2mmol/L in blood serum
25
Causes of hypocalcaemia?
Hypoparathyroidism
26
Symptoms of hypocalcaemia
Convulsions
Arrhythmias
Tetany
numbness
27
What are the 2 different types of bone?
Spongy/ trabecular/ soft
and
Hard/ cortical/ compact
28
Cortical bone
Arranged in osteons - consist of concentric lamellae
Covers the bone
Collagen run in opposite directions and there are multiple layers
strong
heavier than trabecular bone
29
Spongy bone
```
Trabeculae
Spaces for red and yellow bone marrow
no blood vessels running through it
much lighter than cortical bone
not as strong as cortical bone
absorbs compressive loads
found on the inside
```
30
What are the 2 different types of bone marrow?
Red and yellow
31
Red bone marrow
Site of RBC production - haemopoiesis
32
Yellow bone marrow
Fat but can convert back to red bone marrow in times of trauma/ blood loss to provide more
33
What are the 2 different types of bone formation?
Intermembranous ossification
| Endochondral ossification
34
Intermembranous ossification
Occurs on or within loose fibrous connective tissue membranes
e.g. flat bones of skull, mandibles and clavicles
35
Process of intermembranous ossification
1. Development of ossification centre - mesenchyme differentiates into osteoprogenitor cells, which differentiate into osteoblasts. Osteoblasts secrete extracellular matrix (ECM) until they are surrounded
2. Calcification - Osteocytes continue to secrete ECM
Osteocytes in lacunae form canaliculi between each other. Deposition of calcium and mineral salts which calcify the matrix.
3. Formation of trabeculae - form from ECM and trabeculae fuse to form spongy bone. Connective tissue in trabeculae differentiate into red bone marrow.
4. Development of periosteum - mesenchyme condenses in periphery of bone. Cortical bone replaces spongy to form the periosteum. Finally, remodelling occurs to create adult size and shape .
36
Endochondral ossification
Formation of bone from a cartilage template. E.g. long bones
37
Process of endochondral ossification
1. Development of cartilage model
2. growth of cartilage model
3. development of primary ossification centre (growth from outwards to inwards)
4. development of medullary cavity
5. development of the secondary ossification centre (growth inwards to outwards)
6. formation of articulations cartilage at epiphyseal plates
38
What are the different types of muscle?
Skeletal
Cardiac
Smooth
39
Cardiac muscle
Striated
Uninucleated
Involuntary/ myogenic
Branched intercalated discs with many gap junctions
Excitation-contraction coupling and calcium induced calcium release
40
Skeletal muscle
```
Striated
Multinucleated
Voluntary
Long
Many mitochondria
Actin/ myosin interaction
```
41
Smooth muscle
```
Not striated
uninucleated
spindle shaped
myosin light chain kinase contraction
involuntary
```
42
Structure of skeletal muscle
Muscle fibre surrounded by endomysium, multiple of these make up a fascicle which is surrounded by the perimysium. Many fascicles make up a muscle, the epimysium surrounds all the fascicles that make up a particular muscle.
43
Neuromuscular junction
1. Action potential arrives at presynaptic knob
2. Causes calcium voltage gated channels to open and calcium ions move in
3. these cause vesicles containing ACh to move to and fuse with the presynaptic membrane
4. Vesicles are released into synaptic cleft by exocytosis
5. 2 ACh molecules bind to the nicotinic ACH receptor and cause sodium ion channels to open
6. Sodium ions enter and cause excitation of muscle cells
44
Muscle contraction stage 1
1. Action potential reaches the muscle cell
2. Depolarisation travels down the T tubules
3. The sarcolemma is depolarised, causing the L-type calcium channels to open and release calcium ions
4. These cause RYRs on the sarcoplasmic reticulum to open and more calcium ions are released
45
Muscle contraction stage 2
1. Calcium ions bind to troponin and cause it to change shape, moving tropomyosin out of the actin-myosin binding sites
2. Calcium ions bind to ATPase and cause it to break down ATP, releasing energy
3. Myosin heads bind to the actin-myosin binding site and form cross bridges
4. The myosin heads rotate in unison and move the actin filament along - powerstroke
5. ATP binds to the myosin heads and breaks the cross bridge
6. The cycle continues
7. Calcium ions are returned to the sarcoplasmic reticulum by SERCA and ATP
46
What are the 3 pathologies that affect the neuromuscular junction?
Myasthenia Gravis
Botulinum Toxin
Organophosphate poisoning
47
Myasthenia Gravis caused by?
Autoimmune that destroys the nicotinic ACh receptors
48
Symptoms and treatment of Myasthenia Gravis
```
Muscle weakness - Gowers sign
Droopy eyelid - Ptosis
Facial paralysis
Double vision
Voice and speech problems
gets worse as the day goes on
treatment = Pyridogostigmine which inhibits AChE
```
49
What causes organophosphate poisoning?
Inhibits AChE
50
Symptoms and treatment of organophosphate poisoning
```
Muscle tremours
confusion
small pupils - miosis
sweating
vomiting
diarrhoea
increased saliva and tear production
treatment = atropine and pralidoxome/ trimedoxime
```
51
What causes Botulinum toxin?
Inhibits release of ACh into the synaptic cleft
52
Symptoms of Botulinum toxin
muscle paralysis
heart failure
respiratory failure
53
Medical uses of Botulinum toxin
AKA Botox
excessive sweating
migraine
cosmetic - anti-ageing
54
Duchenne muscular dystrophy
```
Genetic condition
muscle weakness, loss and paralysis
no treatment
caused by a mutation in dystrophin which is important in cell membranes of muscle fibres
raised creatine kinase
```
55
Bone growth in thickness
Occurs at surface - appositional/ endogenous growth where there is an increase in matrix and cells
56
Process by which bone growth in thickness occurs?
1. Formation of osteocytes
2. Formation of groove for periosteal blood vessels
3. formation of tunnel
4. osteoblasts deposit extracellular bone matrix
5. this forms the concentric lamellae, filling in which forms osteons
6. circumferential lamellae form
7. new vessels form so more osteons form
57
How does bone grow in length?
Exogenous growth that occurs at the epiphyseal plate. There is no increase in cells, but an increase in bone matrix. It finishes between 18 and 25 as the plates close .
58
Process of bone growth in length
1. zone of resting cartilage - anchors epiphyseal plate to epiphysis due to infiltration of capillaries
2. zone of proliferating cartilage - produces chondrocytes
3. zone of hypertrophic cartilage - chondrocytes mature and form lacunae
4. zone of calcified cartilage - cartilage matrix calcifies and osteoblasts and osteoclasts infiltrate and remodel to turn the calcified cartilage into bone. Capillaries from diaphysis infiltrate and anchor plate to the diaphysis
59
What is bone remodelling?
Repairs microstresses and microfractures, making bones stronger. It Involves resorption by osteoclasts and deposition by osteoblasts.
60
What are the stages of bone remodelling?
1. Quiescence - resting state
2. Resorption - break down of bone by osteoclasts
3. Reversal - macrophages clear up the debris left by osteoclast activity
4. Formation and mineralisation - preosteoblasts and osteoblasts lay down new bone
61
What are the 3 stages of bone fracture repair?
Reactive phase
Reparative phase
Bone remodelling
62
What happens at the reactive phase?
Blood vessels are broken and so there is a bleed. Clot forms - fracture hematoma. Bone cells die causing swelling and inflammation. Phagocytes and osteoclasts remove dead or damaged tissue around the hematoma.
63
What happens at the reparative phase?
1. Blood vessels grow into the fracture hematoma
2. phagocytes remove dead bone cells.
3. Fibroblasts produce collagen and chondroblasts produce fibrocartilage
4. Repair tissue bridges cartilage and collagen fibres which form the fibrocartilaginous callus
5. In healthy bone tissue osteoprogenitor cells form osteoblasts. Osteoblasts make trabeculae which join living and dead bone tissue and convert fibrocartilage into spongy bone.
64
What happens during bone remodelling?
Osteoclasts resorb dead portions of the dead bone fragments.
Cortical bone replaces trabecular bone on the periphery of the fracture
65
What hormone is responsible for the closure of the epiphyseal plate?
Oestrogen in early adulthood
66
What factors affect bones?
Age
Gender
Race - africans have higher mineral bone density
Genetics
Hormones - T3, T4, hGH, oestrogen, calcitonin and PTH
Dietary intake - vitamin D and calcium
Physical activity
67
What is osteoporosis?
Disease in which the density and quality of bone is reduced so they become more porous and fragile.
68
What causes osteoporosis?
```
Diet
Eating disorders
Menopause
Old age
Genetics
Alcoholism
Other diseases
```
69
what are the symptoms of osteoporosis?
Back pain from collapsed or fractured vertebrae
Loss of height over time
Bones that break more easily than expected
Stooped posture
70
What are the treatments for osteoporosis?
```
Biphosphates - alendronic acid
PTH
Calcium and vitamin D supplements
Hormone replacement therapy
Selective oestrogen receptor modulators - SERMS
```
71
How is osteoporosis diagnosed?
DEXA bone density scan
72
What are some more bone related pathologies?
Giantism
Acromegaly
Rickets
73
What is Rickets?
Due to a lack of vitamin D, leads to weakened bones. Causes characteristic bowed legs outwards in children and forwards in adults. In adults it is called Osteomalacia
74
What is Acromegaly?
Caused by oversecretion of hGH after closure of the epiphyseal plates. Causes enlarged face, hand and feet bones
75
What is giantism?
Oversecretion of hGH before closure of the epiphyseal plate - so during childhood. Causes people to grow to 7-9ft and be generally bigger boned.
76
What is the basic structure of a long bone?
```
Ends = epiphysis
Shaft = diaphysis
Between shaft and end = metaphysis
In the centre = medullary cavity
Lining medullary cavity = endosteum
Outer covering of bone = periosteum
On epiphysis at a joint = articular cartilage
```
77
What is the metaphysis?
Between the epiphysis and diaphysis, contains the epiphyseal plate and then the epiphyseal line when the hyaline cartilage is converted to bone.
78
What is the role of the articular cartilage?
Hyaline cartilage that covers the epiphysis at a joint, acts as a shock absorber and reduces friction
79
What is the purpose of the medullary cavity?
Hollow cylindrical cavity in the centre of the diaphysis that contains marrow and blood vessels
80
What lines the medullary cavity?
Endosteum - a thin membrane that contains a single layer of bone forming cells and connective tissue
81
What covers the outside of the bone?
Periosteum, which is a tough connective sheath that has an outer fibrous and inner osteogenic layer. It acts as a point of attachment for ligaments. Attached to the bone by perforating fibres
82
How is bone a connective tissue?
Widely separated cells
large amounts of matrix material - collagen, elastic fibres and matrix
Collagen provides flexibility
83
What cells are in connective tissue?
```
Fibroblasts
adipocytes
macrophages
leucocytes
mast cells
```
84
What do fibroblasts do?
Produce collagen and elastic fibres - active in tissue repair
85
What do adipocytes do?
Fat store
86
What do macrophages do?
Engulf and digest cell debris
87
What do leucocytes do?
White blood cells
88
What do mast cells do?
Release heparin, histamine and other substances in response to cell damage
89
Benefit of collagen fibres running in opposite directions in cortical bone?
Resist twisting forces
Prevent cracks spreading
allow more strength
90
Cartilage
connective tissue made up of chondrocytes and large amounts of matrix material
Avascular
no innervation
91
What does the matrix material in cartilage contain?
Chondroitin sulphate, collagen and elastin fibres
92
Role of collagen in cartilage?
provides strength
93
Chondroitin
Provides resilience and gel like remodelling characteristics in cartilage. Chondroitin sulphate is a sulphated glycosaminoglycan
94
Bone vs cartilage
Bone is hard and cartilage flexible
| Bone has lots of nerves and blood vessels and cartilage has none. Bone is metabolically active but cartilage is inactive
95
Why does bone have blood vessels through it?
Diffusion cannot occur through it so a rich blood supply is required. In cartilage diffusion can occur - but badly and so it takes longer to heal than bone.
96
Differentiation osteoclasts
Haematopoietic stem cell > common myeloid progenitor > granulocyte macrophage progenitor > osteoclast
97
Differentiation of osteoblast. adipocyte/ chondroblast and myoblast
Mesenchymal stem cell
98
What vitamins are involved in bone growth?
A, C, D, K and B12
99
Role of vit. A in bone growth?
Stimulates osteoblast activity
100
Role of vit. C in bone growth?
Synthesis of collagen
101
Role of vit. D in bone growth?
Absorption of calcium
102
Role of vitamin K and B12 in bone growth?
Synthesis of bone proteins
103
Which part of a bone is ossified from the primary ossification centre?
Diaphysis and epiphyseal plate
104
Which part of a bone is ossified from the secondary ossification centre?
Epiphysis
