Notes from the Video

What am I going to learn today?

Today we're going to continue our discussion on the metabolic response to injury and if you haven't watched the first video I discussed the major stimulants following injury: pain hypovolemia and circulating stuff. 

This video is critical when it comes to understanding today's topic, how the body changes following injury and how fuel is utilized. 

Yes I want to watch the Metabolic Response to Injury video

Now that you have that under your belt we're going to be confident learning three major topics today:

1.   Understanding the ebb and flow stages of recovery

2.  The metabolic changes after injury and how metabolites are utilized

3.  Injury and fuel

A few questions...

Why is it beneficial to give your patient a little bit of dextrose perioperatively, what does that do?

How can you appropriately change the content of your TPN in that critically ill patient?

Why do you not want to give too much dextrose to that critically ill patient who is at risk of developing hepatic steatosis beyond?

The Ebb Phase of Injury

Immediately after injury we have the ebb phase and that's shutdown mode.

This occurs in the first minutes to hours following injury and that's where you can see the beaches, the tide is out, nothing's happening.

The Flow Phase of Injury

The next phase is the flow phase, here you can see the water rapidly coming into the bay and that's where the stimulation by pain with secretion of catecholamines, norepinephrine and epinephrine, and their respective downstream effects.

Pain anxiety and fear stimulate CRH release from the hypothalamus to the anterior pituitary with cortisol release from your adrenal glands and then all the downstream activity of cortisol.

In addition, aldosterone and ADH is released for volume preservation.

In the flow phase you have increased substrate utilization with increased cardiac output and an increase in the metabolic rate.

Fat is the preferred energy during trauma, the preferred metabolite. 

Amino acids are going to be liberated from the skeletal muscle to produce the acute phase proteins.

There is going to be a negative nitrogen balance as you have increased nitrogen excretion through the urine.

Metabolism can increase 15 to 30 percent during this flow phase.

The Recovery Phase of Injury

In the recovery phase the boats are sailing, everything is good, this is the anabolic state.

The anabolic state is the only state where you can actually have protein synthesis and rebuilding of that skeletal muscle that is lost.

The transition from the flow phase to recovery happens within three to eight days after elective surgery and much longer after major trauma sepsis and injury.

This is also known as the corticoid withdrawal phase, where there is a cessation of proteolysis or breakdown of protein from skeletal muscle and an increase in

protein synthesis or rebuilding.

This phase also coincides with the diuretic phase as you have increased oral intake and decreased ADH and aldosterone leading to a diaresis because the body is no longer in that flight-or-fight, where it needs to hold on to its volume.

The Metabolites of Injury

Protein

Protein serves as the greatest glucose substrate following injury.

Now, I didn't say the biggest fuel I said the greatest precursor to gluconeogenesis. 

We know that surgical stress leads to increased protein breakdown and proteolysis leads to increased nitrogen excretion in the urine as we build our acute phase proteins

In the liver this response is proportional to the injury and if we think about it the amount of protein breakdown,  it can be up to 30 grams of nitrogen a day secreted in

the urine.  That's equivalent to 1.5 percent loss of lean body mass a day or up to a kilo of skeletal muscle broken down every day.

Understanding this makes it clear that without nutritional support, which can suppress but not completely eliminate protein breakdown, skeletal muscle loss can be rapid.

In addition that may lead to not having the muscular strength to wean from the ventilator. 

Protein degradation happens really quickly and studies have shown that even within hours of elective surgery you get complete blockade of protein synthesis and increased proteolysis.

Lipid

Lipids are the primary fuel after trauma and injury, why do lipids produce so much energy?

When we look at the amount of energy per gram of metabolites what are the the amount of calories gained per gram of protein. per gram of carbohydrates, and per gram of fat?

Remember, for every gram of protein we get 4 kilocalories, every gram of carbohydrate gets you 4 calories and every gram of fat gives you 9 calories.

Why is that?

Going back to biochemistry, this does have utility as a surgeon!  When we go back and look at what is a triglyceride  some see the following...

That a triglyceride is three fatty acids hooked up to a glycerol, each of those fatty acids can have more than 16 carbons on it.

Linolenic acid is an 18 carbon chain, the triglyceride is broken down in the cytoplasm into fatty acids and glycerol.

The fatty acids go through the carnitine shuttle to get into the mitochondria and that's where fatty acid oxidation occurs.  This creates Acetyl CoA which goes

into the Krebs cycle to produce a bunch of ATP.  All of those carbons produce ATP. 

In addition the glycerol directly enters glycolysis so that's a lot of ATP production per triglyceride!

You probably didn't ever think that would come in handy but it gives you the understanding of why fat is such an awesome resource in trauma and injury.

Carbohydrates

Carbohydrates have a high utility following injury but they can also be dangerous as the carbohydrate that's most important to us is glucose.

I keep saying again and again the metabolic response to injury is to increase glucose.

Humans are glucose burning machines during the normal state but during trauma and injury this all changes, we become fat burning machines.

Starvation is a little bit different than stress because we preferentially break down protein and that serves as precursors to glucose to provide energy.

One of the purposes of an ERAS program in elective surgery is to limit protein breakdown by limiting overnight fasting, giving a preoperative carbohydrate drink and limiting that proteolysis and inhibition of protein synthesis.

We know that giving 50 grams of dextrose a day, that's just a one liter bag of D5 solution.  D5 1/2 NS has a 50 grams of dextrose, that's enough to limit proteolysis, increase fatty acid oxidation and reduce ketogenesis. 

In trauma, sepsis and injury it is totally different than starvation and it's totally different because of the last video you learned that it's not just not consuming the energy for use you have a massive release of pro-inflammatory hormones and cytokines that change everything.

Early in the Ebb phase glycogen is broken down so that you can use glucose but this only happens for 12 to 24 hours following that you rely on renal and hepatic

gluconeogenesis using amino acid precursors as well as lactate and glycerol. 

This increase in the  synthesis of glucose is critical so that you can deliver glucose to cells which do not use insulin for uptake, neurons and red blood cells, leukocytes, inflammatory cells in the wound like fibroblasts and granulation tissue. 

All of these use glucose directly and that's why we need more glucose after injury so we can feed all of these cells.

Lactate is also a very important precursor to glucose.

Biochemically, we bring back to the Cori cycle and that's how we shuttle lactate from peripheral tissues to the liver but know that producing glucose here comes at a loss and it's a cost of 4 ATP for every glucose produced.

During injury and trauma giving a small amount of glucose, you know 50 grams a day perhaps more if you're writing for TPN, and this small amount of glucose suppresses proteolysis, increases fatty acid oxidation, and decreases ketogenesis. 

The cost is that too much glucose leads to hepatic steatosis, excess carbon dioxide production, and suboptimal pulmonary function.

Insulin

We can't talk about carbohydrate utilization or metabolites in general without talking about our good friend insulin.

In the normal state insulin is secreted from the beta cells of the pancreas, the islets of Langerhans..

Insulin reduces muscle protein breakdown, stimulates lipogenesis and prevents lipolysis.

Now take the stress state.  In a stressed state, glucagon, catecholamines, cortisol, growth hormone and cytokines are all released and that leads to increase free fatty acids and amino acids in the bloodstream.  This suppresses insulin secretion and eventually creates insulin resistance.

This resultant hyperglycemia leads to a pro-inflammatory response.

Exogenous insulin is required to return glucose levels to the normal state and this leads to improved surgical outcomes and reduced morbidity.