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Why do muscles grow in size after weightlifting or other types of resistance training?

The answer is both more straightforward and more complicated than I realized.

Let’s get “swol”...

#Tweetorial #MedTwitter
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First, a review of skeletal muscle physiology:

The fundamental unit of muscular contraction is the sarcomere, made up of actin and myosin proteins.

Myosin slides along actin in an ATP-dependent fashion, shortening the sarcomere, inducing contraction.

https://pubmed.ncbi.nlm.nih.gov/11331913/ 
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Sarcomeres line up in parallel and are bunched into myofibrils.

Myofibrils pack together to make muscle fibers, which comprise skeletal muscle.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193686/
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I assumed the answer to this question was simple - hypertrophy.

But there are 3 phases to muscle growth w/ exercise:

✅ Muscle pump (immediate swelling)
✅ Inflammatory (delayed swelling, hours-days)
✅ Hypertrophy (days)

Let’s break each one down. https://pubmed.ncbi.nlm.nih.gov/30335577/ 
Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise - PubMed

One of the most striking adaptations to exercise is the skeletal muscle hypertrophy that occurs in response to resistance exercise. A large body of work shows that a mammalian target of rapamycin...

https://pubmed.ncbi.nlm.nih.gov/30335577/
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✅ First, there is immediate swelling (within minutes of exercise).

💡Not surprisingly, blood flow to exercising muscle increases dramatically to meet metabolic demands.

https://pubmed.ncbi.nlm.nih.gov/3318504/ 
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Blood flow ⬆️ to muscle during exercise b/c of the so-called muscle pump.

Contracted muscle squeezes valved veins, pushing blood through w/ contraction and pulling in more blood w/ relaxation. 

🔑This "pumped" blood flow leads to rapid swelling.

https://www.ncbi.nlm.nih.gov/books/NBK57139/ 
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✅ Next let's look at delayed swelling (hours-days).

The load from weightlifting causes microdamage to sarcomeres, as actin and myosin are pulled apart w/ forced contraction.

💡This is known as myotrauma and is a normal part of resistance training.

https://pubmed.ncbi.nlm.nih.gov/2222798/ 
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Myotrauma releases Damage Associated Molecular Patterns (DAMPs).

DAMPs recruit macrophages, neutrophils, and lymphocytes into the recently-exercised muscle.

🔑Associated prostaglandin release and vasodilation causes delayed muscular swelling.

https://pubmed.ncbi.nlm.nih.gov/10805959/ 
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✅ The final phase, and source of longterm growth of muscle after weightlifting, is hypertrophy.

💡Studies after weight training show an increase in muscle fiber surface area without an increase in the number of fibers, consistent with hypertrophy.

https://pubmed.ncbi.nlm.nih.gov/8941522/ 
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Why do muscles hypertrophy after resistance training? It has to do w/ repair of damaged fibers.

We already saw that exercise ➡️ myotrauma and macrophage recruitment.

Macrophages also activate a type of muscle stem cell called satellite cells (SC).

https://pubmed.ncbi.nlm.nih.gov/22833472/ 
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Satellite cells normally reside in a quiescent state in muscle.

⚡️Macrophages secrete IL-6, which recruits and activates them (as do circulating growth factors).

SCs then proliferate and form tube-like structures within the damaged myofibrils.

https://pubmed.ncbi.nlm.nih.gov/10805959/ 
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Satellite cell aggregates secrete actin and myosin, which get incorporated into the damaged myofibrils, repairing and expanding them.

🔑 This leads to hypertrophy and growth of muscle in the days after exercise.

https://pubmed.ncbi.nlm.nih.gov/10805959/ 
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In essence, we can distill down the increased size of skeletal muscle after weight training to two factors:

1⃣Increased blood flow (short term)
2⃣Repair of myotrauma (longterm)
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The next time you workout and your muscles grow, the following events will have occurred:

💪 Immediate swelling (increased blood flow from the muscle pump)
💪 Delayed swelling (inflammatory response to myotrauma)
💪 Hypertrophy (new protein deposition from tissue repair)
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