Infection and Massive Fibrin Amyloid formation

THE CARCO STRESS MODEL: Carbon Monoxide Exposure → Infection →  Extensive Peroxynitrite Formation in Capillaries → Extensive Fibrin Amyloid Formation → Microvascular Obstruction → Reduced Mitochondrial Oxygen Availability → Aerobic Energy Production Failure → Rapid Systemic Dysfunctions

The Role of Neutrophils During Inflammatory Stress

During a severe infection, major injury, or surgery, neutrophil production increases several-fold. This means vastly more neutrophils are available to participate in carbon monoxide-related fibrin amyloid formation. If carbon monoxide exposure occurs during this high-neutrophil period, it may form an excessive amount of abnormal amyloid structures.

Persistence of Fibrin Amyloid Structures

Because fibrin amyloid structures resist normal physical breakdown, the structures formed during this period persist after the infection, injury, or exposure ends. These dense structures accumulate and progressively obstruct a greater number of microvessels over time.

The Sequence of System Failure

• Severe infection, major injury, or surgery increases neutrophil production.
• Overlapping carbon monoxide exposure occurs.
• Massive fibrin amyloid formation takes place.
• Microvascular obstruction increases progressively.
• Tissue oxygen delivery is severely reduced.
• System dysfunctions and organ failures occur.

An Integrated Biological Hypothesis

This complete sequence has not been directly demonstrated as a single continuous observation. It is an integrated biological hypothesis connecting several experimentally observed physical processes into one continuous mechanism.

Severe Infection and Massive Neutrophil Production

Normal Neutrophil Production

Neutrophils are the most common type of white blood cell in the human body. They form a critical physical part of the innate immune system. The human body normally produces roughly 50 to 100 billion neutrophils every day.

Neutrophil Functions in Immune Defense

Neutrophils help the immune system fight infections and heal physical injuries. These cells function as the primary defense mechanism against harmful pathogens like bacteria and fungi.

Massive Production During Severe Stress

During severe infection, major injury, or other strong inflammatory stress, neutrophil production increases several-fold. The body can increase production toward approximately one trillion neutrophils per day to manage the stress.

Prolonged Inflammatory Stages

A complicated clinical course can involve several consecutive inflammatory stages. A major injury can lead to surgery, postoperative tissue repair, and a secondary infection. Each physical stage increases and prolongs neutrophil production and activation.

Elevated Neutrophil Counts Over Time

Neutrophil counts remain approximately two to five times above control levels during the first five days of stress. Significant elevation is still physically present around day ten. Serious infections can produce similarly prolonged cellular responses.

Neutrophil Dynamics in COVID-19

In severe and critical COVID-19, longitudinal measurements show altered and increasing neutrophil counts. These elevated counts occur across approximately days 10 to 28 of illness before returning toward normal levels during convalescence.

continuous exposure during illness

Normal Interruptions in Exposure

A person normally spends much of each day outside the home at work, school, or elsewhere. If a low-level carbon monoxide source or repeated infiltration exists at home, these periods away from the building interrupt the exposure and allow blood levels to decline.

Continuous Indoor Exposure During Illness

During an infection or recovery from an injury, a person may suddenly spend almost 24 hours per day indoors for several weeks. Staying indoors increases total carbon monoxide exposure. This also reduces the physical opportunity for the gas to be cleared from the body.

Changes in Exposure Duration

The carbon monoxide source does not need to change to cause harm. What changes is the amount of time the person spends in the contaminated environment. An exposure that normally occurs part-time becomes almost continuous during the exact period when the inflammatory response is strongest.

Accumulation and Insufficient Air Exchange

A continuously operating source is not required for exposure to continue. If carbon monoxide has accumulated indoors and air exchange is insufficient, the source can stop while the gas remains in the breathing environment. Repeated releases prolong this physical accumulation further.

Relevant Exposure Patterns

Relevant carbon monoxide exposure patterns include:

• One larger exposure
• Repeated low-level exposure
• Continuous low-level exposure

A massive increase in neutrophils during an infection combined with prolonged indoor carbon monoxide exposure drives severe fibrin amyloid formation and systemic microvascular obstruction.

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