Blood and its roles in homeostasis, infection, and cancer

Blood is a specialized fluid connective tissue that supports and connects all body systems [1, 2, 8, 11, 13]. Its three main functions are transport, regulation, and protection, with each being a vital component of sustaining life. It is made up of about 55% plasma and 45% formed elements, with plasma being the nonliving, fluid matrix [9]. Working together, the cells and substances inside of blood keeps the body working by connecting all systems; however, this connection can pose significant complications as some things we wish to stay isolated, such as infections and cancers.

Formed elements are red blood cells (erythrocytes), white blood cells (leukocytes), and platelets [1, 2, 8, 11]. Erythrocytes are responsible for transporting oxygen from the heart and lungs to cells throughout your body. They also carry waste, such as carbon dioxide, away from your cells to be excreted by the lungs and kidneys. Leukocytes are a main component of the immune system and are responsible for protection against pathogens and other foreign invaders. They prevent and fight infections along with eliminating cancerous threats in ways similar to that of infections. Platelets, with the help of proteins found within the plasma, prevent blood loss (hemostasis) and disease spread via clot formation. Blood transports hormones to and from organs, which is one of the ways that blood regulates the body and maintains homeostasis. An example of this can be seen in antidiuretic hormone (ADH), also known as vasopressin, and it is made by the hypothalamus and stored in the pituitary gland, both of which are found within the brain. ADH then travels via the circulatory system, acting upon the kidneys and blood vessels to maintain adequate fluid volume. Additional ways that blood regulates bodily systems and functions is by absorbing and distributing heat to maintain body temperature and using buffers to regulate pH. 

The circulatory system, also known as the cardiovascular system, is a one-way system that comprises the heart, lungs, arteries, veins, capillaries, and venules [2]. If blood and its components were cars, then the circulatory system is the highway in which they drive on. It begins and ends with deoxygenated blood entering the lungs; fueled passively by a pressure gradient, erythrocytes are ready to trade their waste for oxygen in what is known as gas exchange. Once the blood is oxygenated, it enters the left side of the heart before being pumped through and out into the aorta, where it then travels via arteries and capillaries to the rest of the body. When the oxygenated blood has run its course, tissues having successfully exchanged waste for oxygen and nutrients, it returns back to the heart via veins and venules, this time entering the right side. Finally, the deoxygenated blood is pumped into the lungs again, and the process starts over.

Blood pressure naturally causes some leakage from blood vessels, where it accumulates in interstitial spaces, which are the spaces between cells and tissues [2, 4, 8]. Most of the excess fluid gets reabsorbed back into the blood vessels, but the fluid that is left behind gets taken up by the lymphatic system; it later gets deposited back into the circulatory system. Once this excess fluid enters the lymphatic system, it is then referred to as lymph. The lymphatic system is also a system that leukocytes can conveniently use to get from interstitial spaces into the circulatory system. The immune system is heavily integrated into the lymphatic system, making the two systems barely distinguishable from one another. Organs in this system include lymph nodes and vessels, tonsils, the spleen, thymus, bone marrow, and more.

The immune system is equipped with a vast amount of defense mechanisms, protocols, and pathways to prevent infection and other dangerous occurrences. When pathogens - infectious agents that cause a reaction from the immune system, like bacteria, viruses, and fungi - evade and/or defeat these defenses, then infection ensues. 

Antigens are the specific substance or molecule that cause the immune system reaction; all pathogens contain antigens, but not all antigens are pathogenic, as some antigens are allergens, such as dust, pollen, and pet dander/hair. Additionally, not all allergens are antigenic, i.e. not everyone is allergic to the same things. These concepts are in the same vein as “all squares are rectangles, but not all rectangles are squares”.

The first line of defense comes from the innate immune system, which describes the cells and substances that someone’s body is born with the ability to make  [1, 2, 8, 11]. The first line, specifically, includes the physical and chemical barriers that protect the body from the outside environment, such as skin, mucus, gastric acid, the normal microbiome, hair, nails, etc. These defenses act as armor and repel a vast amount of pathogens and antigens. The next line of defense, for when the first line fails, comes again from the innate immune system, but this line is more about cellular responses than cellular barriers; for example, the inflammatory response (which is then followed up by the third line: the adaptive immune system, the acquired immunity that your body learns as it is exposed to environmental factors, such as pathogens). 

The inflammatory response, which is typically paired with clot formation, is a mechanism to prevent the spread of infection and to signal distress to nearby blood vessels, which in turn recruits more immune molecules and cells to the site of infection  [1, 2, 8, 11]. When an infection does spread, it does so via the circulatory or lymphatic system (some pathogens can produce toxins which can spread infection as well). Upon entering these systems, the infectious agents now have the means to travel anywhere in the body, which is a known precursor for sepsis and septic shock [9, 12]. 

The infection can trigger an inflammatory response wherever it goes, recruiting more molecules, more cells, and facilitating the formation of more clots [3, 9, 12]. This strong immune response is known as sepsis and it can progress into septic shock, which is when organs begin to shut down due to lack of blood flow and oxygen from the inflammation and clots. Much like any serious health concern, it is crucial to seek medical attention for sepsis immediately. 

There are infectious and pathogens that can lead to cancer, such as certain HPV strains. Cancer can also occur due to cell replication errors - mutation - which happen randomly, by chance [17]. Random mutations make up about 60% of all cancer cases, and the remaining 40% can be attributed to things such as environmental factors, lifestyle, genetics, certain infections/pathogens, etc.

A normal cell is able to monitor and regulate itself and/or others to make sure no abnormalities are occurring [2]. When replicating, there are a series of checkpoints that a cell must pass in order to continue, such as the mitosis G1/S checkpoint [7]. During these checkpoints, DNA damage and errors are assessed and repaired. The cell cycle stopping to allow for repair is known as cell arrest. If the damage cannot be repaired, then the cell undergoes apoptosis, which is when a cell self-destructs. This is crucial in making sure the correct genetic information is passed on to the new cells and any cells that contain the wrong information gets stopped in their tracks. If DNA damage or errors are not recognized and cell replication proceeds, the new cell now contains what is considered mutated DNA that will get passed on during future replication. Depending where on the DNA the mutation(s) occurred, they can be harmless in the sense that the affected gene may be non-essential or non-active, thus never presenting any detectable issues. However, if this mutation happens to take place on a gene that normally aids in an important process, such as regulating cell growth, the gene not functioning as needed may cause serious illness. In the event it is a vital cell growth regulating gene, known as oncogenes and tumor suppressor genes, it can cause unchecked and uninhibited cell division, leading to uncontrollable replication and proliferation. This type of cell growth is known as cancer. 

Some cancerous cells may move or drift from their original location in what is known as metastasis, however it is not an easy feat [14, 18]. Cancerous cells do not often survive in the circulatory system as they get met with 3-4 mph turbulent conditions. With an environment too harsh, many of the cancerous cells die before they find a way out. 

When cancerous cells find themselves somewhere new after successfully traveling through the body - whether that be via the circulatory system, lymphatic system, etc - medical professionals can often identify where it metastasized from because the cells will resemble that off of where they came from [6, 14, 18]. This means that even if lung cancer has spread to the bone, they will still be lung cells, which are distinguishable from one another under a microscope. Cancers whose origins cannot be identified are known as Cancer of Unknown Primary Origin (CUP). Furthermore, while cancer can spread anywhere, there are locations that are more probable based on the flow of the circulatory system. For example, colon cancer commonly metastasizes to the liver because before blood that is transported to the colon returns back to the heart and lungs, it travels to and through the liver.

Similarly to infection, the body has mechanisms to prevent and fight cancer [2, 5, 8]. Natural Killer (NK) cells, part of the innate immune system’s second line of defense, are one of the few leukocytes equipped to fight cancerous cells head-on. They can be found in many areas of the body, such as the lungs, lymph and lymphoid organs, and blood. Their methodology can be described as “extracellular killing” because they are able to recognize a cell as abnormal based on the structures found on the outside of the cell. NK cells have killer-inhibitory receptors (KIRs) that bind to major histocompatibility complex class one (MHC-1) that is found on the surface of all nucleated cells (and platelets). When this KIR-MHC-1  connection is made, the NK cell becomes inhibited and does not kill the cell. Abnormal cells will sometimes lose their MHC-1, making them a target for NK cells. If the NK cell were to try and bind to said abnormal cell then it would result in the NK cell not being inhibiting, subsequently allowing it to kill the abnormal cell. The NK cell achieves this by releasing perforin, a protein that pokes holes in the cell membrane, which allows cytotoxic molecules to enter and trigger apoptosis. Cytotoxic T-cells, part of the adaptive immunity, can also kill abnormal cells in a similar fashion where they recognize antigens found on MHC-1 proteins, rather than recognizing the MHC-1 itself. 

Blood keeps all cells fed, oxygenated, healthy and alive. The circulatory system acts as highways for erythrocytes (and thus oxygen), leukocytes, nutrients, waste, ions, hormones, and more, including the not-so-helpful substances, like pathogens and cancer. The lymphatic system, which runs side-by-side with the circulatory system, helps return fluid and leukocytes back into the blood. Also found in the blood are platelets, which are essential in clot formation to maintain hemostasis and prevent infection spread. With the infection sealed off from the rest of the body, leukocytes come in to fight the pathogens and clean up the mess afterwards. Leukocytes are also able to fight cancer, such as NK cells and cytotoxic T-cells. Ideally, though, cells will be able to detect cancer within themselves and undergo apoptosis, as 60% of all cancer cases are due to random replication errors. 

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All diagrams and artwork are produced and made by Myr Selvage

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