Muscle Adaptation, damage and repair - NMSK

hypertrophy

cells/muscle fibres increasing in size - increase in myofibrils, increase in myofilaments

how does hypertrophy change muscle size?

cross sectional area increases, muscle length stays the same

hyperplasia

increasing the number of cells

atrophy

a reduction in muscle volume or mass, which may be generalised or limited to certain muscles/types (there can be a specific reduction in type 1 fibres for example).

What anabolic factors cause hypertrophy?

• human growth hormone

• mechanical load - builds up the muscle. muscle often needs damage to stimulate an increase in muscle mass

What catabolic factors cause atrophy?

• disuse

• denervation - loss of nerve supply to the muscle

• disease

• malnutrition

What hormones are involved in an increase in fibre size?

• insulin like growth factor 1 (IGF-1) stimulates muscle growth.

• IGF-1 is stimulated by human growth hormone

What are some examples of muscle pathology?

• trauma

• nerve damage

• disease

• aging

What cells are involved in muscle repair following injury and what do they do?

• satellite cells - type of adult stem cells

• are activated following damage

• they proliferate and differentiate to form muscle cells and daughter cells

When does and doesn't scarring occur following injury?

• muscle will heal by scarring if the basement membrane has been damaged

• satellite cells allow muscle to repair without scarring, but can only occur if the basement membrane has not been damaged

What is the issue with scarring?

it results in scar tissue which is non-functional/ not contractile

Outline a timeline of what would be seen in histology during injury and repair of muscle.

• 3 days after injury - lost muscle cells, clusters of activated satellite cells

• 5 days after injury - myotubes formed, can go on to differentiate into muscle cells

• 7 days after injury - regenerating fibres back to normal size

How can nerve damage cause muscle loss?

motor nerve damage can lead to lack of innervation of muscle, which causes the muscle to undergo atrophy

How can muscle damage be clinically detected?

• myoglobinuria - when muscle damaged, myoglobin (the o2 binding protein in muscle) can leak into the bloodstream. this can lead to excessive amounts of myoglobin in the urea. can detect the myoglobin in urine. too much myoglobin in urea can cause kidney damage.

• creatine kinase - enzyme used by muscle to convert creatine into creatine phosphate and vice versa. it is released during muscle damage so increased levels can indicate muscle damage or wasting.

What is the drawback of creatine kinase as an indicator for muscle damage?

it is very sensitive - can be released in response to very small amounts of damage. therefore it doesn’t indicate what level of damage there is in the muscle.

What are the major causes of disease in skeletal muscle?

• inflammatory

• congenital and inherited

• endocrine and nutritional

• exertional

• metabolic

What is polymyositis?

• generalised inflammatory myopathy

• muscle damaged thought to be the result of cell-mediated immunity

What is masticatory muscle myositis (MMM) and what are the clinical signs?

• focal inflammatory myopathy that selectively affects the muscle of mastication (chewing)

• clinical signs: trismus (lock jaw), fox like contour of the head, prominence of zygomatic arch (extends from the temporal bone)

What is an example of a congenital/inherited myopathy, what is its cause and what does it cause?

• Duchenne Muscular Dystrophy

• occurs in humans, dogs and mice

• caused by a mutation in the gene coding for the membrane protein dystrophin (x-linked recessive disorder)

• causes degeneration and eventually failure of the respiratory muscles

What are some examples of endocrine myopathies, their causes, clinical signs and what they lead to?

• hypothyroidism - atrophy of type II fibres. clinical signs include weakness, stiffness, reluctance to move, decreased exercise tolerance and muscle wastage. causes problems with carbohydrate metabolism which interferes with glycolytic metabolism.

• cushings disease (hyperadrenocorticism) - selective atrophy of type II fibres. clinical signs include muscular weakness, stiff gait, muscle atrophy, and inability to walk in dogs. causes break down of muscle proteins and inhibition of muscle protein synthesis.

What is an example of a nutritional myopathy, which animals it affects and what the clinical signs?

• selenium/vitamin E deficiency

• disease of calves, lambs, swine and foals

• clinical signs: still birth, weak calf - stiffness and inability to stand.

What are exertional myopathies?

myofiber damage occurring as a result of exercise stress as the primary cause.

What is an example of an exertional myopathy, what are the 2 types, clinical signs?

• exertional rhabdomyolysis

• types: sporadic vs recurrent

• sporadic - one-off event, occurs due to exercise in excess of current fitness. causes acidosis and too much heat which damages the proteins.

• recurrent - repeated events that can occur even after light exercise. can be different types of recurrent. often genetically induced.

• clinical signs - muscle injury, myoglobinuria, weakness, recumbency in heavy horse breeds. episodic muscle pain, sometimes swelling and reluctance to move in light horse breeds.

What is an example of a metabolic myopathy, what’s its cause, what are the clinical symptoms?

• equine polysaccharide storage myopathy

• abnormal accumulation of glycogen in the muscles

• caused by a glycogen synthase 1 mutation

• clinical symptoms - tying up painful muscle cramps.

What is sarcopenia, and what is involved?

• atrophy associated with ageing (slow degeneration)

• loss of motor axons, denervation, degeneration, loss of motor fibres/axons, motor-unit size, fibrosis.