The Neurological Waste Removal System – Glymphatics pt. 1 

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The Body’s Waste Removal System

Many of you have heard of the lymphatic system – the waste removal system of the body that is responsible for clearing out cellular debris, fluid, and inflammatory byproducts. The lymphatic system is found throughout the body and is comprised of multiple organs including the spleen, tonsils, adenoids, and the thymus gland. Lymph nodes are small, bean shaped organs that are located along lymph channels to help pump and remove lymphatic fluid, the waste product of the various systems of our body. Lymph nodes are located deep within the body along our limbs, but also strategically placed around our internal organs too. What’s interesting regarding the lymphatic system though, is that while it is well understood for the body, it is not as well understood for other areas of the body – in particular – the brain! But before we dive into this newly understood system, let’s discuss how and why our body must regulate energy and waste removal.

The human body is exceptionally capable of taking care of itself. It comprises a vast system of internal organs, nerves, various connective tissues, and many other structures alike. These tissues each have specific functions from support, energy production, signal transmission, secretion, elimination, and more. While the body is infinitely self-sustaining when given the right tools to support an optimal internal environment, maintaining that self-sufficiency requires several mechanisms to take place. One of these mechanisms includes the removal of harmful byproducts of cellular metabolism in our body. 

The body is a multitude of complex structures and systems that work coherently to generate life. In order to give expression to that life, we must produce energy. In order to produce energy, we must consume enough food, get enough hours of sleep at night, drink enough water – the general staples of well-being. Energy, in its most broken down form, is found within a molecule known as ATP – adenosine triphosphate. This molecule is composed of a single adenosine molecule with three separate phosphate groups attached. The energy from ATP is found within the bonds of the molecule – stored up until we cleave off a phosphate group, resulting in the release of energy. While our one portion of metabolism includes the formation and utilization of adenosine-triphosphate (ATP), we must also be able to clear out the remaining waste after ATP has been utilized. This is akin to CO2 emissions from gasoline burning vehicles – we have to be able to “burn off” our emissions that are created from the energy producing cells in our body. 

So what does this waste build up process look like? Examples of this can be found all over the course of our day in many of the different actions we perform – eating, drinking, exercising, and even simply breathing. They can include when we contract a muscle over a brief period of time during a bicep curl, and even when we are fighting off pathogens. When we exercise, we  utilize phosphocreatine to generate adequate levels of ATP in muscle fibers, leaving behind creatinine and broken down myofibrils – both of which must be removed in order for proper muscle tissue healing to occur. When we fight off a virus, our immune system detects a foreign pathogen and initiates a response that includes increasing our metabolism. This increased metabolism demands a higher energy requirement from ATP to fuel the immune cells to fight off the virus, part of the reason why we will commonly develop a fever.

Following this immune process, dead cellular debris and neutralized viral cells must be eliminated in order to prevent chronic inflammation and buildup of unnecessary materials. Waste elimination takes many forms in the body and is utilized throughout every region and is paramount to overall health optimization. What’s exciting about this is that it wasn’t until recently that research began focusing on this component of the human body – further deepening our understanding of not only how we neutralize substances, but what our bodies must then do, and what structure are involved, in order to eliminate byproducts before they can cause harm. 


What is the glymphatic system?

Now that we have a deeper understanding of energy generation via ATP, the lymphatic system and its included structures, and basic understanding of waste removal, let’s further discuss another part of our lymphatic system that is so aptly named the glymphatic system – aka, the lymphatic system of our brain.

The reason the glymphatic system is referred to as such is due to it’s association with our formal lymphatic system of the body, while being tightly regulated by a major group of cells within our central nervous system called glial cells. The primary form of glial cells are found within the central nervous system (CNS) and include astrocytes, microglial cells, and oligodendrocytes. These types of cells have multiple purposes and are incredibly important for our CNS to function at it’s most homeostatic, efficient state. Because glial cells perform multiple actions and constantly fluctuate in activity, their rate of energy consumption is high. Having a higher energy consumption therefore results in their waste products to be significant and abundant too.

The glymphatic system receives cerebrospinal fluid (CSF) and interstitial fluid (ISF) waste from the brain and drains into the peripheral lymphatic system of the body. Not only does the glymphatic system eliminate waste created from the brain, it will also remove any excess waste that is able to pass through the structures protecting the brain in the first place. There is a tightly regulated barrier between the brain and the venous-arterial system surrounding it - named the blood-brain barrier (BBB) - which is responsible for strictly controlling neurotransmitters, solutes, molecules, ions, and various other materials from entering the brain that are either beneficial or harmful. While under physiological conditions, the BBB is capable of preventing damaging materials from passing through. However, metabolic disease, neurological dysfunction, trauma, malnutrition, and various other conditions are capable of weakening the BBB and allowing unnecessary waste products and damaging molecules to pass through unscathed.

It goes without saying that allowing these types of damaging substances through will only further a diseased state. Transport through the BBB functions via ion channels, tight junctions, aqua-porins, and other gated substrates, and once through the BBB, substances are further distributed via a penetrating vascular system and ventricular system. In various areas of the brain, we have ventricles that house our CSF, a fluid wildly important in clearing the brain of toxins, cellular debris, soluble proteins, and metabolic products. This fluid then joins ISF to be drained out of channels known as aquaporin-4 (AQP4) channels into a space known as the virchow-robin space (VRS) – a region histologically defined as a space that surrounds the venous arterial system beneath the subarachnoid space, or the space between the pia mater and arachnoid mater of the brain. From the VRS, the combination of CSF and ISF will eventually drain into the peripheral lymphatic system via the jugular vein and join the rest of the body’s waste material. 

The reason the glymphatic system deserves increased attention is due to the growing body of literature demonstrating the significant overload of waste material found in patients diagnosed with some of the more common neurological diseases. Patients with Alzheimer’s, Parkinson’s, dementia (of the Alzheimer’s type and not), neuro-autoimmunity, PANS/PANDAS, concussions, and many more have been shown to have a significantly increased levels of waste products in the brain, and furthermore a dysregulated removal system of those products. In several of these diseases, there is altered brain neurochemistry due to inflammatory over-dominance, that when left unchecked, results in further damage and dysfunction. Allowing a pro-inflammatory state to remain untreated only results in disease progression and worsening of symptoms. So while addressing key components of these diseases outside of the brain is important, ensuring that we’re providing the optimal environment for the brain to rid itself of toxins and pathogens is also vital. Due to the glymphatic systems relationship to removing waste material from the brain, providing treatment to this system could provide a therapeutic benefit. 

Next Up

In a future blog post, we’ll be exploring the physiological mechanisms that are more common in some of the previously mentioned diseases, their pathogenesis or progression, and what therapies can be applied to these key systems in order to provide the ultimate benefit for the patient. What can be said for now is that ensuring that your provider is digging as deep as they can with your condition and history so that you are receiving the care you deserve. 

If you have any questions, please reach out to our clinic and providers, we’d love to help you in any way possible.