By Nana Dadzie Ghansah
Note: This is but a very simple discussion of very complex pathologies. It is in no way an exhaustive treatment of the topics touched on.
“I cannot so properly say that he died of one disease, for there were many that had consented, and laid their heads together to bring him to his end. He was dropsical, he was consumptive, he was surfeited, was gouty, and, as some say, he had a tang of the pox in his bowels. Yet the captain of all these men of death that came against him to take him away, was the consumption, for it was that that brought him down to the grave.” — from “The Life and Death of Mr. Badman” by John Bunyan (1680)
Diseases caused by pathogens — bacteria, viruses, fungi, and parasites — have been with us for eons. Among them, those that affect the lungs — pneumonias — have always been lethal killers. In antiquity and until about the 20th century, tuberculosis (the consumption) was, as described by John Bunyan in 1680, “the Captain of These Men of Death”. In 1901, William Osler conferred this unflattering distinction on Pneumococcal pneumonia. With the advent of vaccines and antibiotics, pneumonias are not the number one killers but they still place 4th worldwide as a cause of death. The offensive agents are bacteria like Streptococcus pneumoniae and Haemophilus influenzae that cause community-acquired pneumonia (CAP), viruses like Influenza A and B and the novel COVID-19.
Although a 4th cause of death worldwide, there are regional differences. In the US, pneumonia is the 7th leading cause of death but in Ghana, it is the 2nd.
Why are pneumonias so lethal? To understand that, we need to explore why infectious diseases kill. To do that, one has to first get the concept of “shock” as used in medicine.
Shock is the condition where the vital organs in the body — brain, heart, lungs, kidney, liver, intestines — are not getting enough oxygen.
We humans breathe in air that contains 30% oxygen into our lungs. The oxygen diffuses from the lungs into the blood and is carried by the blood to all the organs of the body. Now since oxygen is carried around by blood, blood flow can be used most times as a proxy for oxygen supply.
The flow of blood around the body can be likened to the flow of water through pipes in a water supply system, so let’s see if we can dig into the concept of shock with an analogy.
Let’s take any major city. Most major cities have a central water supply. From a reservoir, a pump or pumps drive water to homes in the city so when you turn your faucet on, water gushes out.
Now imagine very little or no water trickles out when you turn the faucet on. What could be wrong?
Could the pump(s) be defective? Has the reservoir lost water leading to a shortage? What if a bunch of pipes have started leaking leading to a drop in pressure? Is there a major blockage in the system?
If we see the body as the city, blood as water that needs to get to every organ (home), the heart as the pump and the blood vessels as the pipes, then we can also deduce the four kinds of shock states that are seen in practice.
Shock due to the heart not pumping well because of say, a heart attack is called cardiogenic shock. If the outflow of blood is blocked, like when there is a clot in a vessel that goes to the lungs (pulmonary embolus), we have obstructive shock. Massive blood loss due to an injury like a car accident can lead to hypovolemic shock. The last type of shock is called distributive shock and that takes a bit of discussion too.
Blood is composed of about 90% water in which various compounds are dissolved. Suspended in this are the platelets, white and red blood cells. The blood vessels in which they flow are usually competent and do not allow leakage except at the level of the capillaries. This is where the exchange of nutrients and waste products takes place. However, in certain disease states, the blood vessels become leaky and the water from the blood leaks out sort of indiscriminately into tissue. This leads to a significant reduction in the supply of oxygen to the vital organs. This is what constitutes distributive shock and it is the type of shock that is often caused by infectious agents.
To go from an infection to distributive shock, one has to first get to a condition called “sepsis”. To illustrate that, we will use pneumonia as an example.
We begin by thinking of what happens when we take a breath. Air rushes through our nostrils, into the back of our mouth and then goes down the trachea. The trachea branches off into the left and right bronchi, each one going to a lung. The right lung is made of three parts or lobes and the left two. Each bronchus divides several times, sending branches to each lobe. The branching finally ends in the very slim bronchioles. At the end of each bronchiole hangs a cluster of tiny grape-like air sacs called alveoli. There are over 30,000 bronchioles and each has a cluster of about 1000 alveoli hanging from it like grapes.
Now around each tiny alveolus is a network of capillaries to allow the exchange of gases (oxygen and carbon dioxide) from the alveolus into the blood and vice versa. The total surface area from the over a million alveoli used for gas exchange is more than 100 square meters.
The capillaries are naturally “leaky” so this gas exchange can happen. The wall of the alveolus is also permeable to gases. To help keep the alveoli from collapsing together, they are lined by a substance called pulmonary surfactant.
Now imagine a bacterium or a virus coming along and infecting the lungs. It does so mostly at the level of the alveoli though it can also be higher. Usually, the infection is also in one lung though it can be both. Bacteria usually infect lobes while viruses cause more of bilateral patchy infections. Once these pathogens attack the alveoli, they start to destroy them, breaking down their walls and filling them with debris.
The immune system of the body senses this invasion and the cells that fight infection — the white blood cells — congregate around the area of the infection. These cells then try to eat up the pathogens (phagocytosis). The white cells release chemicals like cytokines to attack the pathogens. Others like nitric oxide, serotonin and histamine, cause the capillaries to open up more allowing even more “fighter cells” to show up. This intense attack by the immune system leads to the alveoli filling up with debris, fluid, and pus. The longer this goes on, the wider the “fight” fans out and the more alveoli and thus areas of the lung are affected.
This is then what is called Pneumonia. The patient coughs, has difficulty breathing, is running a fever and looks ill. Antibiotics, given early, can really shorten this reaction.
If however antibiotics are not given on time or the antibiotics do not work or it is a viral infection against which no therapy exists, the disease can progress. The patient may need to be intubated (have a tube placed in the trachea) and connected to a ventilator for support. Artificial coma is usually induced for this phase.
The intense immune reaction of the body to an infectious agent or a noxious stimulus is called inflammation.
At this point, the “fight” between the body’s immune system and the pathogens — the inflammatory reaction — can start affecting the whole body. (The disease can prove fatal even at the very early part of this stage). This “turning-on-the-body” by the substances released by our immune system to attack the pathogen causing pneumonia, is termed “sepsis”.
Sepsis occurs when the chemicals released by white blood cells and other components of the immune system to fight an infection lead to an iflammatory reaction in the whole body.
Sepsis has three stages and until the very last stage it is still possible to save the patient.
The first stage is called, well, “sepsis”. The effects of the immune substances make the fever persist. Heart rate goes up and blood pressure falls. Not only does the patient get antibiotics but he or she needs a lot of intravenous fluids and may also needs drugs like norepinephrine to support the blood pressure. (One needs some blood pressure to drive the circulation of blood and supply of oxygen.)
At this stage of sepsis, another condition can beset the poor lungs already dealing with pneumonia. This condition is called Acute Respiratory Distress Syndrome (ARDS). This rather serious condition seems to be the reaction of the lungs to serious illnesses like sepsis or serious trauma like burns or serious car accidents with multiple injuries.
ARDS — The Berlin Definition
ARDS is an acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue…[with] hypoxemia and bilateral radiographic opacities, associated with increased venous admixture, increased physiological dead space and decreased lung compliance.
In a patient with pneumonia who may have a hard time breathing but is still managing with oxygen through a mask, there will be a sudden and dramatic deterioration. Their breathing becomes extremely labored and one may hear a gurgling when they breathe. This is because a majority of the alveoli gets filled with fluid. There are hardly any alveoli left for gas exchange. The patient with ARDS always needs a ventilator for breathing. To help improve oxygenation, patients sometimes have to be positioned prone in the bed. A bed that rotates the patient around 360 degrees is the next step. Sometimes these measures do not work. At this point, these patients have to undergo a procedure where a tube is inserted into a big vein like the femoral vein to run the blood out of the body into an external oxygenator and then pumped back into the body through the jugular vein. The procedure is called Extracorporeal Membrane Oxygenation (ECMO). This is the only way to keep ARDS patients alive when one cannot get any oxygen into the body through the stiff and fluid-filled lungs. The condition has a mortality of over 50% and even those who survive end up with permanent damage to their lungs.
(Now, in heart failure, a similar picture can present of the lungs being full of fluid. However, the history, clinical picture and tests like echocardiography which show how the heart is beating, can help make the diagnosis.)
If things do not turn around, we enter the second stage called “severe sepsis”. One starts seeing hints of distributive shock. The blood vessels start getting leaky. Blood flow to the organs starts to drop. The kidneys are usually affected first and urine output drops. Products of anaerobic metabolism like lactic acid start appearing in the blood. Even at this stage, the patient can still be saved. However, if measures are unsuccessful and we hit “septic shock”, the classic example of distributive shock, then it is all over. All the major organs fail in a process that is almost like an avalanche and death ensues as the heart, not getting enough oxygen, will go into a lethal rhythm or just quit.
These events are not seen only with pneumonias. Most infections can take this course if treatment is delayed. It can be a tooth abscess, a urinary tract infection, a diabetic sore or even appendicitis, one can get septic and go into shock if an infection is not treated promptly. In developing countries where the incidence of death through infectious diseases is high, delay in getting treatment means that a lot of patients show up already septic or even in severe sepsis, making the chances of recovery slim.
As the world grapples with the COVID-19 virus, some people are going to develop pneumonia if they get infected. Even though the progress of the disease may be slightly different, the development of sepsis, ARDS and shock are what may ultimately kill the unlucky ones.