Muscle Pathology Flashcards
Since muscle is such a metabolically active tissue, when there is a problem, what are two things you need to consider?
Nutrition and toxins
What are some signs of muscle disease?
Atrophy, hypertrophy (response of a muscle tissue to outside stimulus), swelling/ oedema, weakness (nutrition, innervation, etc.), muscle spasm (calcium, neural muscular junction problem), abnormal gait (weakness or problem with innervation, may be changes in bone or tendon too), oesophageal dysfunction (a lot of species have skeletal muscle in oesophagus)
What is the best indicator of muscle damage from a blood test?
Serum Creatinine Kinase
Cachexia
Loss of muscle conditional from malnutrition or following cancer for example
With a traumatic wound to muscle, what are clinical considerations long term?
Keep joints moving, it will repair itself and regain function.
Major consideration with muscle direct injury?
Vascular injury and causing necrosis. Increasing pressure locally can close off blood vessels. If pressure exceed vascular or arterial pressure we can get necrosis. e.g. horse in lateral recumbency during surgery- weight on any muscles (or organs really)
Indirect injury to muscles?
Blood borne (pathogens, toxins, immune complexes), immune mediated damage
Physiological muscle dysfunction?
Excess tension or excess force it can rupture (i.e. wild animal in captivity), exercise induced damage, loss of innervation (i.e. trauma), anything that causes a loss of blood supply (= necrosis, you will lose muscle function), endocrine/ electrolyte imbalance (disrupting calcium you can get necrosis, e.g. malignant hyperthermia in pigs)
Genetic muscle dysfunction?
Usually structural- improper innervation, lack of function of neural muscular junction. Muscle doesn’t define how it functions until it get innervated
Nutritional/ Toxic effects on muscle?
Deficiency of selenium/ vitamin E (whiteness in muscle = necrosis), toxic plants, feed additives, toxins
a. Blood vessel
b. Perimysium
c. Epimysium
d. Fasicle
e. Endomysium
f. Muscle fiber (cell)
Swelling of muscle tissue inside the fascia, what happens?
Fascia puts pressure on the blood vessels, lose blood supply and ischaemia.
Where does the pain come from in a muscle injury?
Nervous problem. Even if it is muscular dystrophy, the pain is from the inflammation, not the muscle itself.
What are satellite cells and what is their function?
Stem cells that generate new tissue when muscle is injured. Very few satellite cells. Signals from macrophages cause them to come out of acquiesence.
Where is the nucleus for a skeletal fiber?
Nucleus is always on the periphery. If the nucleus is in the middle, it can be a marker of damaged muscle (possibly chronic, but either way the damage is happening now)
What are the different types of muscle fibres? Resistance to fatigue?
What stains dark in muscle fibers?
Which type of muscle fibers use what kind of fuel?
What are the relative size comparisons?
Lots of Mitochondria (so the most in slow twitch type I)
*low glycolytic capacity compared to fast twitch (especially type IIb)
* the white fibers do not have much mitochondria in them ( quite large compared to the ones with mitochondria)
Motor Unit
What is true regarding a fiber type and its innervation?
A motor nerve and all of the muscle fibers it innervates. Within one muscle there can be multiple motor units.
**Each muscle fiber in a muscle is only innervated by one nerve.
**All slow oxidative fiber types are only innervated by nerves which innervate slow oxidative fibers.
What are the two manifestations of atrophy?
Symmetric and Unilateral
Why does a muscle atrophy?
Lack of trophic support coming from the nerve (growth factors, for example). Not about loss of neural musclar junction and electrical activity. Depending on the typer of innervation the pattern of atrophy is unique.
What are the differential effects of atrophy; fibre types?
As you get older, what type fibres do you lose first?
Type 2 fibres- think of elderly, can’t catch themselves when they trip up because they have lose their fast fibers.
What is this?
Atrophic fibre surrounded by normal fibres.
What are you looking at here?
Large group of atrophy, generalized. Increased concentration of nuclei (haven’t increased the number, just the density)
What happens when we lose innervation?
- Atrophy of fibres because we’ve lost trophic support
- Another motor neuron sprouts and attaches– if they are different type fibers– then the fibers can convert to the motor neuron
Fibre Type Grouping
One motor unit knocked out, another takes over, and all of the fiber types become the same type.
(You can get the angular fibers first, then reinervation, and now it can regenerate with the new trophic support)– if the blood supply remains to keep them alive, they are just losing protein.
Hypertrophy- compensatory in response to loss of functional fibres (increased load on the remainder)
Alterations in normal metabolic processes
What is a neuromuscular junction?
Motor neuron meets the individual muscle fibre. Not physical, just very close. Should only see one NMJ per muscle fiber (multiple end buds of the nerve, but it is all one NMJ).
What is arthrogyropsis?
Crooked joint
Defective innervation
Histologically similar to denervation (nerve is still there though but some reason the NMJ is not operating properly)
Genetic, teratogenic viruses or toxins, nutritional: vit A and manganese (esp. pigs)
Pigs, Cattle (hard to tell if it is a bone problem, muscle problem, tendon problem, etc.)
** This is from the muscle not growing in utero
What is Myotonic?
Temporary inability of muscle fibres to relax
Histologically normal (NMJ problem, almost like a acetylcholine esterase inhibitor)
“fainting goats”- the muscles do not relax. It is a spasm of the muscle, happens when someone scares it or when it has to contract the muscle. Not a fear response, but when you contract your muscle, NMJ has to function.
What is congenital forelimb flexural deformity?
NMJ problem- looks similar to arthrogyropsis. Crooked joints.
What is Myasthenia gravis?
Autoimmune disorder. The body generates antibodies which binds to the acetylcholine receptor, which means the signal does not get across the junction. You can sort of move, but the movements aren’t well coordinated.
What is Rhabdomyosarcoma?
Rapid growth, malignant. Rarely metastasis to skeletal muscle. Thought to arise from satellite cells or other precursors.
How else can you affect the NMJ structure (other than congenital or autoimmune disorders?
Botulinum toxin and tick paralysis- not getting release of neurotransmitter across the NMJ.
What does it mean if muscle is green?
Infection
What does it mean if the muscle is pale?
Necrosis or denervation
What does it mean if there is pale streaking?
Mineralization, myofibre necrosis, or mineralization, infiltration by fat or collagen
What does it mean if muscle is dark red?
Haemorrhage, inflammation, rhabdomyolysis
Necrosis (probably blood vessels cut off in this case)
Pale streaks
Mineralization, myofibre necrosis, or mineralization, infiltration by fat or collagen
Rhabdomyolysis
Breakdown of muscle tissue that leads to the release of muscle fiber contents into the blood. Often cause kidney damage and blood in the urine.
When necrosis is segmental it involves? What about global?
Segmental- involvement of only one or several contiguous segments within the cell
Global- affects entire length. Only under extreme circumstances; pressure to the entire muscle such as a crush injury or ischaemia or burns.
Necrosis- internalized nuclei, pale staining areas.
Inflammation
Hyaline Degeneration happens first
Contraction of the muscle fiber (hypercontracts), do not have nice striations, it looks glassy (smooth and shiney)
Second: you get floccular degeneration
Lose muscle nuclei. Lost all of the structure of the skeletal muscle fibre.
In skeletal muscle damage, you can also see mineralization. Calcification. In this section, a lot of inflammation and mineralization. Once you get mineralization, you are losing function because you’ve disrupted the sarcomere.
When you get damage in muscle, what pattern of inflammation do you see? Continuing on with the steps of generation.
- Phagocytic macrophages (clean up the necrosis)
- Macrophages that aid regeneration- release factors that recruit satellite cells. Tell the precursors where the damage is.
- Leukocytes, neutrophils, eosinophils, DCs come
This is clearance, NOT an infection type of inflammation. Not as organaized. It is called “Sterile Inflammation.” You havent gotten external contamination in.
- Satellite cells come in- proliferation within basal lamina (Connective tissue) surrounding individual muscle fibre. They line up and fuse together to form a long tube/ chain to replace the muscle fiber within the tube of connective tissue.
** end up with regenerated muscle fibre with internal nucleus (ongoing regeneration)– will move outside after a week or so.
Successful muscle regeneration depends on
- Presence of intact basal lamina (most common problem- damage to connective tissue and scar tissue formation therefore loss of function, not as flexible, doesn’t contract like normal muscle)
- Availability of viable satellite cells
Ineffective regeneration
- Disrupt basal lamina- destructive lesions (trauma that transects fibres), GIANT CELLS
- Decreased satellite cell viability (extensive injury (heat, extreme inflammation or infarction); healing by fibrosis)
Giant Cells (satellite cells in the context of skeletal muscle)- no scaffold to know where to regenerate. “Bags of cells”- disorganized. You still get muscle fibres but very disorganized and function is compromised.
What are things that cause muscle ischaemia?
Occlusion of major blood vessel, external pressure on a muscle (crush), swelling of muscle (compartment syndrome), vasculitis/ vasculopathy
Downer Cow Syndrom
Muscle ischaemia. More weight= occlusion of blood vessels= ischaemic damage and necrosis. 6 hours or more= extensive damage.
Reperfusion injury
Too much calcium influx all at once, blood supply happening again after cow gets up for example. Oxidative damage can happen as well (oxygen in too quick = free radical production).
Compartment syndrome
Increased intramuscular pressure leading to ischaemia myodegeneration
Muscles surrounded by tight fascia.
White Muscle Disease
Selenium/ vitamine E deficiency
They are antioxidants. Skeletal muscle is highly metabolic, uses oxygen, creates oxygen free radicals, if you don’t have the system to clear those- you can get damage to muscle. Selenium and vit E are very important.
Myofibril degeneration. Esp. livestock with rations like silage, proprionic acid (creates glucose) but it breaks down and affects viatmin E.
Exertional Myopathy (Capture Myopathy)
What are some types?
What is an effective regenerative gap width?
e.g. Wild animal in captivity- if the animal moves around too much- you rupture your muscles, myofibrils, blood vessels.
If exercise induced, usually the animal has an underlying metabolic nutritional defect.
*Can also be exertional rhabdomyolysis in horses
Effective regeneration- 2-4 mm gap
If gap is above 2-4 mm, the repair becomes ineffective. There is a limit on how well you can regenerate an injury.
Kink in muscle fibre (compared to the others). Kink suggests hypercontraction. They don’t run in a nice parallel way.
What is a common species of bacteria that causes muscular damage?
Clostridial- damage to myofibres, vasculature, toxemia
You get suppurative and necrotising, suppurative and fibrosing, haemorrhagic
Blackleg in sheep for example. Doubly wammy- affecting muscle fibres themselves- necrosis. And affecting blood supply- so you can’t regenerate.
Gas bubble formation in necrotic muscle- blackleg. In infection, you get a lot of gas. If it gets big enough it will start occluding blood vessels. You can see it is a gas bubble because it is lined nicely.
Inflammatory myopathies- what else?
Viral and parasitic
Muscular Dystrophy
Dogs with muscle weakness and atrophy due to muscular dystrophy. Also fat builds up in muscle.
Malignant Hyperthermia
* Unregulated release of Ca++
* Excessive contraction
* Generation of heat (increase body temp)
* Can be triggered by halothane or stress
* genetic- you can breed this gene out of pigs
