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MSK: Physiology Flashcards

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1
Q

How many bones are in the adult human skeleton? How does this differ to the newborn skeleton and why?

A

206 in adult.
Newborns have around 300 but many bones fuse together.

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2
Q

How many bones are in the appendicular skeleton?

A

126

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3
Q

How many bones are in the axial skeleton?

A

80

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4
Q

Bones can be classified by shape. What are the 5 different shapes of bone?

A

Long
Short (cuboidal in shape)
Flat (can be curved e.g. skull)
Irregular (e.g. vertebra)
Sesamoid (round, oval nodules in a tendon - patella is the largest)

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5
Q

Bone can be classified into two different types of macro structure; cortical or trabecular. Both types can be within one bone.
Describe cortical bone.

A

Cortical bone is compact. Dense, solid, only spaces are for cells and blood vessels.

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6
Q

Bone can be classified into two different types of macro structure; cortical or trabecular. Both types can be within one bone.
Describe trabecular bone.

A

Spongy.
Network of bony struts (trabeculae), looks like a sponge. The holes are filled with bone marrow and blood vessels.

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7
Q

Bone can be classified into two different types of micro structure; woven or lamellar. Both types can be within one bone.
Describe woven bone.

A

Woven bone can be made quickly in response to growth/fracture. It is disorganised with no clear structure.
Woven bone is replaced over time by lamellar bone.

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8
Q

Bone can be classified into two different types of micro structure; woven or lamellar. Both types can be within one bone.
Describe lamellar bone.

A

Lamellar bone is made slowly. It has an organised layered structure and looks like tree rings.

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9
Q

Bone is a composite.
What is the percentage composition of bone?

A

50-70% mineral: hydroxyapatite.

20-40% organic matrix: type 1 collagen (90%) & non-collagenous proteins (10%).

5-10% water.

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10
Q

How is the collagen and mineral in bone arranged?

A

Collagen assembles in fibrils with mineral crystals situated in the gaps in between fibrils.

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11
Q

What stem cells do osteoblasts originate from?

A

Mesenchymal stem cells (same as adipocytes, myoblasts, and fibroblasts).

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12
Q

What stem cells do osteoclasts originate from?

A

Haematopoietic stem cells.

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13
Q

What cells do osteocytes originate from?

A

Osteoblasts (which have become entombed in the bone).

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14
Q

What are the two main function of osteoblasts?

A

Produce osteoid to form bone.
Secrete factors e.g. RANKL that regulate osteoclast activity.

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15
Q

How to osteoblasts form bone (osteoid)?

A

They produce type 1 collagen and mineralise the extracellular matrix by depositing hydroxyapatite crystal within collagen fibrils.

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16
Q

What is the main function of osteoclasts?

A

Reabsorb bone by dissolving mineralised matrix with acid and breaking down collagen with enzymes.

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17
Q

How often are bones completely replaced via bone remodelling?

A

Every 10 years.

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18
Q

Describe the structure of collagen.

A

Amino acid chains (2x alpha 1, 1x alpha 2 chains) form triple helix collagen molecules (tropocollagen).
Multiple triple helices form collagen fibrils.
Multiple collagen fibrils form collagen fibres.

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19
Q

Which part of the type 1 collagen molecules bind to each other to form a fibril?

A

Telopeptide (straighter part of the molecule, not helix).

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20
Q

Which part of the collagen molecule is removed for the collagen to be synthesised into bone, and can be used as bone turnover markers to assess how much bone is being synthesised?

A

N and C end terminals.

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21
Q

Covalent intra/intermolecular (within and between) crosslinks binds the triple helix molecules into fibrils. What essential trace element is needed to form these crosslinks?

A

Copper.

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22
Q

Why is vitamin C required to form collagen?

A

Vitamin C converts Fe3+ (iron in diet) to Fe2+ (more easily absorbed).
Fe2+ is needed to form molecules within the collagen triple helix (hydroxyproline), which are vital for collagen structure as they form hydrogen bonds between each other.

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23
Q

What enzyme secreted by osteoclasts breaks down collagen?

A

Cathepsin K

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24
Q

Alkaline phosphatase inactivates pyrophosphate by hydrolysation.
Why is alkaline phosphatase an important enzyme for bone mineralisation?

A

Pyrophosphate prevents unwanted calcification and helps regulate bone mineral density.
Pyrophosphate binds strongly to the surface of growing hydroxyapatite crystals, disrupting the structure and preventing crystal growth.

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25
Intramembranous ossification describes the process of ossification from mesenchymal stem cells without a cartilaginous template. What bones form via intramembranous ossification?
Flat bones of the skull. Mandible & maxilla. Mid-clavicle.
26
The majority of bones form by endochondral ossification. Briefly describe the process of endochondral ossification.
Mesenchymal stem cells become chondrocytes whuch hypertrophy. Hypertrophic chondrocytes build cartilage matrix. Osteoblasts build osteoid onto the cartilage matrix. Chondrocytes die off, leaving space for vasculature to invade.
27
What is the epiphysis and why does it contain a secondary ossification centre?
The epiphysis is the end of a long bone in children, and is mostly cartilaginous in infants. It contains a secondary ossification centre to turn the cartilage into bone throughout childhood.
28
At what age is peak bone mass reached?
About age 25.
29
What is the function of collagen in bone?
Allows flexibility/elasticity (toughness). Creates structure for hydroxyapatite crystals.
30
What is the difference in calcium distribution between the main reservoir of calcium in the skeleton, and the extracellular calcium?
1200g in the skeleton. 1g in the extracellular space.
31
Calcium in the blood is distributed in three ways; ionised, complexed, or protein-bound. What is the main protein binding calcium?
Albumin.
32
What happens to ionised calcium in the blood at high pH? Why does this cause tingling when hyperventilating?
More calcium binds to albumin, so there is less bioavailable ionised calcium. This causes problems with nerve signalling and muscle contraction, which needs ionised calcium to function normally.
33
What is the recommended daily intake of calcium?
700mg/day.
33
What are the two ways in which calcium is released from bone?
Rapidly, from exchangeable calcium on the bone surface. More slowly, by osteoclasts during bone resorption.
34
98% of calcium filtered by the glomerulus is usually reabsorbed in the nephron. Why does this change when filtered sodium is high?
Ca2+ and Na+ are co-transported, so if Na+ is high and the kidneys need to excrete more, Ca2+ will also be excreted.
35
What is calcitonin?
Hormone produced by thyroid C cells when serum calcium raised. Effect is to lower bone resorption. Significance in humans is uncertain, more important to animals living in high calcium environment e.g. fish.
36
Calcitriol (active vitamin D) binds to VDR receptors in intestinal epithelial cells. How does this increase absorption of calcium?
Binding of calcitriol to VDR receptor stimulates production of key active transport proteins which are needed to move calcium from the intestinal lumen into interstitial fluid (where it can then enter blood).
37
How is calcium absorbed in the intestines in a high calcium diet?
By passive paracellular transport.
38
What percentage of total body phosphate is in bone mineral?
90%
39
What is the recommended daily intake of phosphate?
700mg/day.
40
What hormone is the major regulator of phosphate metabolism?
FGF-23 (fibroblast growth factor 23).
41
What cells produce FGF-23 (fibroblast growth factor 23)?
Osteocytes.
42
What triggers osteocytes to release FGF-23 (fibroblast growth factor 23)?
Rise in phosphate levels.
43
What are the two main actions of FGF-23 (fibroblast growth factor 23)?
Increases renal excretion of phosphate: decreases expression of Na+ transporters in the renal tubule. Decreases gut absorption of phosphate: downregulates synthesis of 1α-hydroxylase, which is responsible for converting vitamin D to its active form.
44
Osteoclasts have podosomes which attach to the bone surface, creating a sealing zone. What does the osteoclast secrete which requires this sealing zone to protect other bone areas?
Hydrogen and chloride ions, which form hydrochloric acid, which breaks down hydroxyapatite into calcium and phosphate. Enzymes such as cathepsin K which break down type 1 collagen.
45
Growth factors, hormones, and cytokines can all stimulate osteoblasts/osteocytes to release RANK (Receptor Activator of Nuclear factor) Ligand. What is the function of RANK Ligand?
RANK Ligand binds to RANK receptors on osteoclast precursors, stimulating osteoclast formation, and mature osteoclasts, stimulating osteoclast activity and survival.
46
What is the function of OPG (osteoprotegerin)?
OPG binds to RANK-ligand before RANK-ligand can bind to RANK receptors, thus preventing osteoclast formation/activation/survival.
47
How does exercise stimulate bone remodelling?
Network of osteocytes in bone are distorted by fluid flow shear stress when mechanical stress/load applied. Repeated loads are detected by receptors on osteocytes, which then trigger osteoblasts to strengthen bone. Osteocytes can also activate osteoclasts directly (via RANKL).
48
Wnt is a glycoprotein involved in several aspects of bone formation and bone resorption, for example, Wnts act on osteoblast precursor cells and promote their differentiation into mature osteoblasts. Name another glycoprotein which inhibits Wnt from binding to receptors, and therefore inhibits bone formation.
Sclerostin.
49
How do the three structural classifications of joints relate to the three functional classifications of joints?
Fibrous joints are synarthroses (immovable). Cartilaginous joints are amphiathroses (slightly movable). Synovial joints are diarthroses (freely movable).
50
What are the three types of fibrous/synarthroses joints?
Suture (e.g. skull). Syndemosis (e.g. tibia/fibula) Gomphoses (e.g. teeth - peg in socket)
51
What are the two types of cartilaginous/amphiathroses joints?
Synchondroses (e.g. costal cartilage of the ribs) Symphyses (e.g. intervertebral or pubic symphysis)
52
What are bursae?
Fluid filled sacs lined by synovial membrane that help to cushion and reduce friction at a joint. They can be separate to or communicate with the synovial capsule.
53
Why is articular (hyaline) cartilage important in synovial joints?
It's almost frictionless, and resists compressive loads.
54
Where does synovial fluid come from?
Cells in synovial membrane modify synovial fluid from plasma.
55
What is a ligament?
A fibrous connective tissue, which can have some elasticity, that connects bone to other bones, to augment mechanical stability.
56
What is a tendon?
A tough band of fibrous connective tissue that usually connects muscles to bone to enable movement.
57
Give an example of where tendons do not connect muscle to bone.
Eyeball; tendons attach extraocular muscles to the eyeball itself.
58
Why are tendons and ligaments slow to repair after damage?
Tendons and ligaments have a poor blood supply, and a small number of fibroblasts in comparison to fibres.
59
What happens to collagen fibres in a tendon/ligament when a first initial load is applied?
Collagen fibres first straighten out due to a degree of 'crimping' before coming under tensile force.
60
Ligaments and tendons are viscoelastic. Which has more elastin, ligaments of tendons?
Ligaments (tendons can have small amount of elastin).
61
Which has more organised fibres, ligaments or tendons?
Tendons.
62
In a load-elongation curve, P-max refers to the maximum deformation and tensile strength of ligaments/tendons, beyond which there is progressive failure of collagen fibres. During normal activities, what is the maximum degree of tissue elongation, in percentage of P-max?
Normally only 30% of P-max.
63
What encapsulated sensory receptors, located in tendons near the junction with muscle, are activated by stretch or active muscle contraction?
Golgi tendon organs.
64
How do golgi tendon organs prevent muscle/tendon damage through the inverse myotatic reflex?
Golgi tendon organ sense over-stretching of muscle/tendon and sends nerve impulse to spinal cord. Synapses with interneurone which then synapses with motor neuron innervating the muscle, causing muscle relaxation.
65
How do tendons and ligaments change in response to exercise?
Collagen fibres increase in diameter - ligaments become stronger and stiffer, increase in tendon tensile strength.
66
How do tendons and ligaments change in response to immobilisation?
There is a decrease in cross-links between collagen fibres - decrease in tensile strength, more elongation.
67
Why do only children, and not adults, get torus fractures?
In children, the bone is not fully mineralised, so the bone can buckle - this is a torus fracture.
68
What is the difference between an extra-articular and intra-articular fracture?
An extra-articular fracture does not involve the joint surface. An intra-articular fracture does extend into the joint space.
69
What are the four stages of fracture healing?
Haematoma (hours). Inflammation (days). Repair (weeks). Remodelling (months to years).
70
In the inflammation stage of fracture healing, what function do haematopoietic cells perform?
Haematopoietic cells clear debris and express repair cytokines.
71
In the inflammation stage of fracture healing, what function do osteoclasts perform?
Resorb dead bone.
72
Explain what three cells are involved in callus formation occurs during the repair stage of fracture healing.
Fibroblasts produce fibrous tissue. Chondroblasts form cartilage. Osteoblasts form osteoid.
73
When does neovascularisation occur during fracture healing?
In the inflammation stage, which occurs in the days following the fracture.
74
What happens during the remodelling stage of fracture healing?
Woven bone structure is replaced by lamellar bone.
75
What components form an actin filament?
2 alpha-helical strands of actin. 2 strands of tropomyosin. Troponin complex bound to tropomyosin.
76
Describe the structure of a myosin molecule.
2 fibrous tails. 2 globular heads.
77
In the sliding filament theory, why is ATP important for cross-bridge dissociation?
ATP hydrolysis induces shape change in myosin head to break the cross-bridge at the end of contraction. (ADP + Pi is then bound to myosin head).
78
Latency period is the time between the action potential arriving at the muscle fibre and when tension can be observed in the muscle. What is the difference in latency period between slow and fast twitch fibres?
Slow twitch fibres have a long latency period, fast twitch have a short latency period (due to more extensive SR containing calcium).
79
Which has more mitochondria, fast twitch or slow twitch muscle fibres?
Slow twitch - because they need prolonged oxidative metabolism.
80
What are the three main energy sources for muscle contraction?
Creatine phosphate. Anaerobic glycolysis. Aerobic (oxidative) metabolism.
81
How does creatine act as an ATP store in muscle cells?
When there is excess ATP in muscle cell, creatine phosphokinase transfers phosphate from ATP to creatine, creating creatine phosphate (and ADP). The reverse can occur when immediate energy is required for short intense exercise.
82
In muscle fatigue, there is progressive weakness of muscle contraction, until there are no further responses. Name three causes of muscle fatigue.
Decrease in ATP synthesis due to shortage of glycogen (aerobic conditions). Increase in lactate levels lower sarcoplasmic pH (anaerobic conditions). Failure from motor neurons to produce/release ACh.
83
A single motor neuron can branch into fibres to innervate several muscle fibres which then function together as a group (motor unit). Why does the ratio of nerve fibres to muscle fibres vary in different muscles?
Muscles which are needed for fine motor control e.g. the hand, can have as low as a 2:1 ratio of muscle:nerve fibres. Muscles which are for gross motor control have a higher ratio e.g. 100:1.
84
What is a motor unit?
All the muscle fibres innervated by a single nerve fibre.
85
What is a muscle twitch?
Contraction of a single muscle fibre by a single stimulus; the smallest unit of muscle contraction.
86
Why is summation necessary?
A single twitch is so small and weak it cannot provide a very effective contraction. Multiple twitches need to be added together to increase the force of contraction.
87
What are the two mechanisms of summation?
Multiple fibre summation. Frequency summation.
88
How does frequency summation cause an increased force of contraction?
The same muscle fibre is stimulated again before fully relaxing, which escalates the strength of contraction until the tension of individual twitches are indiscernible and maximum contraction is reached. This plateau is called tetanus.
89
What enzyme in the synaptic cleft of the neuromuscular junction is responsible for rapidly deactivating ACh?
Acetylcholine esterase.
90
What is end plate potential?
The localised depolarisation of muscle fibre membrane at the neuromuscular junction.
91
End plate potential is the localised depolarisation of muscle fibre membrane at the neuromuscular junction. What causes end plate potential?
ACh (acetylcholine) is released from the nerve terminal into the synaptic cleft. ACh binds to nicotinic cholinergic receptors on the muscle cell membrane. Nicotinic cholinergic receptors are also ligand-gated sodium channels, and ACh binding causes these channels to open. Sodium enters muscle fibre, causing depolarisation and opening further voltage-gated sodium channels.
92
Why is the t-tubule system important?
T-tubules propagate action potentials further into the muscle fibre, close to the SR, to quickly cause SR to release calcium ions.
93
What sort of exercise maximises bone remodelling response to loading?
Irregular, brief high impact with rests between reps e.g. interval training.
94
Trabecular architecture changes with ageing. Are horizontal or vertical trabecuae lost first? Why?
Horizontal. Most loads are vertical e.g. from walking.
95
What are four common purines?
Adenine Guanine Hypoxanthine Xanthine
96
Purines can be exogenous (ingested) or endogenous (synthesised within the body). What are two methods of purine synthesis?
De novo synthesis, or purine salvage - where products of nucleic acid breakdown are recycled.
97
Why does most purine synthesis occur as salvage, where products of nucleic acid breakdown are recycled, as opposed to de novo synthesis?
Purine salvage requires less energy than de novo synthesis.
98
Where does the purine salvage pathway occur?
Mostly outside the liver.
99
What is the end product of purine metabolism?
Uric acid.
100
Uric acid is the end product of purine metabolism. Where is uric acid mainly produced?
In the liver.
101
Gout is caused by deposition of uric crystals in joints. Why could eating lots of red meat and drinking a lot of beer cause gout?
Red meat and beer are high in purines. Excess purines in the body are broken down into uric acid (hyperuricemia). If not all the uric acid can be excreted quickly, it can form uric crystals which accumulate in the joints, causing inflammation, swelling, and intense pain.

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