Infections by certain pathogens readily lead to a sequence of events that can be fatal. To gain some insight into how this might happen, we will look a viral example and a bacterial example.
In ordinary seasonal influenza, more than 90% of the individuals who develop serious difficulties are above the age of 60. But two current forms of influenza A can lead to serious and even fatal situation in younger people. The first is of the H5N1 subtype and is popularly known as the "bird flu". As of now, it is uncommon in the world since it is poorly transmitted from person to person. But when it is transmitted, it has a very high fatality rate. The second is the now familiar H1N1, also known as "swine flu". It, of course, is widespread in the US and only rarely leads to hospitization. But when it does, it causes death in a significant fraction of the patients. For example, in a recent report from Canada, the median age of the critically ill patients was 32 years and the mortality in this group was 14%.
In ordinary influenza, the virus remains largely in the upper airways. But in the dangerous forms of influenza A, the virus can move deep into the lungs, leading to pneumonia. Pneumonia refers to any "inflammation of the lungs with consolidation ("solidification")". In other words, lung tissue removed at autopsy would not have the normal appearance, in which it would be comprised almost entirely of air filled alveoli (spaces where the gas exchange takes place). Instead, many of the airspaces would be filled with fluid and cells, producing a much heavier consistency.
When the usual forms of influenza lead to pneumonia, the virus infects the upper airways rather than the lungs. This then secondarily causes bacteria, which are often of a type normally present, to move down into the lung. The result is a bacterial infection that causes a massive movement of fluid and neutrophils out of the blood and into the alveoli. Elsewhere in the body, this is the usual response to an infection. But in pneumonia all this is much more pronounced.
By contrast, the H5N1 and sometimes the H1N1 subtype directly infect the epithelium lining the alveoli, causing viral pneumonia rather than (or in addition to) bacterial pneumonia. In viral pneumonia, the fluid and cells accumulate in the interstitial spaces of the lung rather than in the alveoli. As more becomes known, it will be interesting to learn why the H5N1 is so much more likely to do this rather than infect the upper airways as is usually the case with influenza.
What causes some of these infections to be fatal? Bear in mind that all of this is extremely tentative. In the case of the H5N1 virus, the molecule it uses to attach to cells is hemaglutinin, and this seems to be different in a way that allow the virus to be released from cells more easily after it is synthesized. But in addition, it has been discovered that the H5N1 subtype tends to cause considerable release of the cytokine TNF-alpha when applied to human macrophages in tissue culture. In other words, as the infection and pneumonia developed, it appears there was a large accumulation of macrophages, and they released unusually large amount of TNF-alpha . Sometimes this is type of situation is referred to as a "cytokine storm". This will be an interesting point to follow as more becomes known, since it might be an important reason why this form of influenza is so often fatal. Mechanisms through which TNF-alpha can become fatal are shock, disseminated intravascular coagulation and ARDS. These are discussed below.
Septic shock can be a consequence of excessive release of TNF-alpha . Sepsis refers to the "presence of pathogenic microorganisms or their toxins in the blood or tissues". Septicemia is nearly the same, except it refers to "pathogens in the blood" only. Shock refers to "inadequate perfusion of the tissues and organs". Low blood pressure is typically involved.
Important effects of TNF-alpha include increased expression of cell adhesion molecules and increased permeability of capillaries. The result is movement of phagocytes and fluid into the tissues. In the right amount, the recruitment of the cells is quite important and helpful. But when too much TNF-alpha is released, excessive recruitment of phagocytic cells and greatly increased movement of fluid out of the blood and into the tissues can lead to septic shock and then perhaps death.
Disseminated Intravascular Coagulation (DIC) refers to the serious and often fatal condition in which small clots form throughout the body, and in such numbers that clotting factors and platelets are depleted. As a result, the blood can no longer form clots. Organ failure can also occur due to the interruption of blood flow by the clots. Also, there is loss of fluid and white blood cells from the blood into the tissues due to increased endothelial permeability. Disseminated intravascular coagulation is indeed also happening with the hyper-inflammatory response in anthrax, as described below. Other serious pathogens, such as the Ebola virus and other hemorrhagic fevers, can lead to this condition. In sepsis, the systemic release of TNF-alpha and IL-1 trigger the widespread formation of the small clots. Disseminated intravascular coagulation also can occur in various other situations, such as malignant cancers, obstetric complications or serious trauma. Malignant cancer cells entering the blood and obstetric complications, for example, can introduce tissue factor into the blood.
Acute Respiratory Distress Syndrome (ARDS) is a serious condition that can rapidly develop in which inflammation of the epithelia in the lungs gets out of hand. The inflammation injures the endothelium so that large amounts of fluid leave the capillaries and enter the lung. Pneumonia can lead to this syndrome, as can inhalation of toxic gases or other damage to the lungs. Trauma can also lead to ARDS with a delay of about one day. The onset of the syndrome is signaled, for example by dyspnea and tachypnea. Once the characteristics of the syndrome develop, mortality is about 50%.
Anthrax is an example of a bacterium that causes considerable problems for the effector mechanisms. The spores of this bacterium are extremely hardy and can live for a long period in the environment. Upon entering the body, they are engulfed by macrophages and taken to lymph nodes. As this is going on, they enter their "vegetative" form and start dividing.
In the vegetative form, the capsules of the bacteria inhibit phagocytosis (various other pathogens have capsules too.) The rapidly growing population of bacteria in the lymph nodes causes hemorrhagic lymphadenitis. Soon the bacteria are entering the blood in large numbers. This by itself might trigger the issues discussed above for fatal influenza.
But it is the toxins released by this rapidly growing population of bacteria that cause the main symptoms and death. One toxin acts on macrophages, and their response leads to a hyper-inflammatory response. One aspect of this is the release of oxygen radicals. But especially important (in one hypothesis), the macrophages release large amounts of the cytokines TNF-alpha and IL-1, which powerfully stimulate inflammation. Septic shock and disseminated intravascular coagulation can occur. Death often follows, typically within two days of the onset of symptoms.