Episode 63 – Getting Swol

Why does weight-lifting increase muscle size?

If you have ever lifted weights, you are likely to recall that in the hours and days after your workout, your muscles started to grow. Not everyone’s muscles grow to the same extent or degree, but this is a fairly standard response to resistance training. On this episode, we break down (literally) exactly why lifting weights causes your muscles to grow.  

All movement requires the actions of muscles, specifically muscular contraction or shortening. The fundamental unit of contraction is called the sarcomere. Sarcomeres are the smallest unit of action in a muscle that ultimately leads to contraction, and are composed of two proteins: actin and myosin. With the help of ATP, myosin slides along actin. This sliding leads to shortening of the sarcomere, and when all of the sarcomeres within a muscle shorten, that’s what we see as contraction of the muscle. When you look at a sarcomere histologically, with a crisscrossed pattern, they resemble tartan. 

If one were to line sarcomeres up in parallel, overlap them with each other and bunch them together, you get something called a myofibril. If you pack those myofibrils together, that’s called a muscle fiber. And muscle fibers are themselves bunched together in structures called fascicles. And fascicles lined up together comprise a skeletal muscle.

There are three phases to muscle growth after exercise, each playing out over different time scales. First is the muscle pump. This causes immediate swelling after working out. The second is an inflammatory reaction, which causes delayed swelling over hours to days. And the third is hypertrophy, which occurs over days.

Perhaps unsurprisingly, blood flow to muscles increases dramatically during weight-lifting to meet the metabolic demands of exercise. This is known as exercise hyperemia. One study in rat legs found that after running, blood flow increased to the muscles 3-fold compared to just making the muscles twitch. 

Exercise hyperemia occurs, in part, as a result of an increase in cardiac output. But a more important mechanism is the muscle pump. During exercise, the muscle around the vein squeezes and pinches it as the contracting muscle fibers increase the interstitial pressure around the vein. This pushes blood out of the vein initially and causes the valves of the vein to close, preventing the inflow of blood. But there is a rebound phenomenon when the muscle relaxes. That valve opens and more blood gets drawn into the vein with the resultant exercise hyperemia. When the muscle squeezes again, in-flow decreases, and with relaxation, you see more hyperemia. This is, in effect, a pump, and it leads to that immediate muscle swelling with exercise. 

The delayed swelling occurs over hours to days. The load from weightlifting causes micro-damage to sarcomeres from the strain induced by resisting gravity. This resistance pulls actin and myosin apart as the muscle forcefully contracts. Picture a web of rubber bands glued together and then being pulled forcefully apart. Some are going to snap. This snapping is called myotrauma and happens every time you do any type of resistance training.

Though we don’t think about the swelling of muscles after exercise as a form of injury, microscopically it is. When myotrauma occurs, this releases molecular mediators called Damage Associated Molecular Patterns (DAMPs). DAMPs are signal flares for the immune system calling out, “hey, there’s tissue damage happening over here, get in here and deal with it”. DAMPs tell the immune system exactly where to go, recruiting macrophages and neutrophils into the muscle to deal with the damage. There is also prostaglandin release leading to vasodilation, capillary leak and swelling.  

Next we see hypertrophy. A 1985 study in the Journal of Applied Physiology recruited twelve participants to do 12 weeks of intense weight training. At the end of this training period, the researchers performed muscle biopsies and found that the total surface area of the muscle fibers had grown, but there hadn’t been any increase in the number of fibers. The muscles had hypertrophied.

The explanation also dervies from myotrauma. After sarcomeres are damaged by weightlifting, those muscle fibers grow in size (hypertrophy) as a result of the response to that damage. The macrophages that stream into the muscle from microtrauma activate muscle stem cells called satellite cell

Satellite cells are stem cells that live in muscle but are normally quiescent. When macrophages enter the damaged muscle, they secrete inflammatory cytokines including IL-6. IL-6 and other circulating growth factors act as wake up signals to the satellite cells, leading them to leave the quiescent G0 state.

Satellite cells then enter three phases: activation, proliferation, and differentiation. Activation is induced by IL-6. The activated satellite cells then begin to divide. After dividing, they differentiate and fuse with each other into myotubes, and also fuse with existing myocytes. Myotubes accumulate within the damaged myofibrils and secrete actin and myosin. All of these myocytes grow in size and the muscle gets stronger. 

Anabolic steroids take advantage of these mechanism in multiple ways, including enhancing proliferation and differentiation of satellite cells, accelerating muscle growth and increasing strength. This is also true for growth hormone, which explains why it is also banned in sports.

Conversely, astronauts experience significant loss of muscle mass during spaceflight. According to NASA, after spending 5-11 days in space, astronauts can lose up to 20% of their muscle. This is all related to gravity, or the near absence of it in space. On earth we are constantly having to resist the effects of gravity to move or lift things. But in space, astronauts don’t have to resist gravity at all to do anything. So their muscles do the opposite of hypertrophy; they atrophy and shrink and weaken. And this has implications beyond just being significantly weaker when returning back to earth. Some emergency re-entry procedures can be quite strenuous and a weakened astronaut is at risk of not being able to complete them. As a result, astronauts spend over two hours per day exercising to try to counteract this atrophy. 

Take Home Points

  1. Immediate swelling of muscles after exercise occurs due to increased blood flow from the muscle pump.
  2. Delayed post-exercise muscle swelling over hours to days results from the inflammatory response to myotrauma.
  3. True muscle hypertrophy is caused by a tissue repair response leading to satellite cell activation out of quiesence. This leads to new actin and myosin production and increased myofibril size.


Click here to obtain AMA PRA Category 1 Credits™ (0.5 hours), Non-Physician Attendance (0.5 hours), or ABIM MOC Part 2 (0.5 hours).

Listen to the episode


Credits & Citation

◾️Episode written by Avi Cooper
◾️Show notes written by Avi Cooper and Tony Breu
◾️Audio edited by Clair Morgan of nodderly.com

Cooper AZ, Abrams HR, Breu AC. Getting Swol. The Curious Clinicians Podcast. January 25, 2023.

This episode was sponsored by Green Chef!

Image credit: https://www.strengthlog.com/biceps-muscles-exercises-workout/

Published by Tony Breu

Tony Breu, MD is an internist/hospitalist who loves asking ‘why’?

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