What is the central dogma of pathology?

 Pathology has been a central pillar of allopathic medicine since the dawn of scientific medicine. However, with respect to medical education, pathology no longer is a stand alone course.  Pathologists must therefore make the underlying message of pathology as clear as possible or get lost in the firehose of information that medical students are subject to from their first day of classes.

The central dogma of molecular biology as enunciated by Crick in 1958 is that information required to run an organism flows from DNA to RNA to protein. It represents the entire field as a flow of information, rather than as a series of molecular interactions. For the student, this is a very attractive proposition, rather than considering molecular biology as a series of endless organic chemistry reactions.  Pathology needs something similar or will forever be viewed at random (uninterpretable) histologic images.

I was taught that “all disease occurs as a response to injury”. Unfortunately, this dogma fails to explicitly recognize that the role of response to injury is highly variable, ranging from those due to external injury alone which requires no host response (e.g. massive trauma) to those where the “injury” is almost by definition trivial (e.g. respiratory allergies).  Further, some injuries are transient and are repaired via regeneration leading to a restoration of homeostasis (acute hepatitis). Other responses, considered under the general heading of repair, maintain homeostasis of a sort but at a functional level below that of the original host. Any injury leading to fibrosis, hyperplasia, metaplasia or hypertrophy all fall into this category. Finally, some responses e.g. autoimmunity or to DNA damaging agents leading to cancer, are destructive to the organism. It is only these latter diseases that can be considered in response to injury.

The diagram (below) that includes these pathways. Consider typical cellular responses to injury e.g. the cardiac hypertrophy in setting of hypertension. The increased tension on the cell is recognized by a suitable cellular signaling pathway. This pathway then triggers a response that includes both C (increased tension generation) and D (increased cell death due to increased ischemia relative to workload).  Or consider an infection leading to direct tissue death (pathway A). The agent is recognized by both innate and acquired immune response (pathway B) leading to an inflammatory response that both killed host tissue (pathway D) and the offending organism (pathway C). On the other hand, a response to an allergen is entirely D.  The key concept it is the ability to maintain homeostasis at the original level of function that distinguishes physiology from pathology.

Just as an aside, "aberrant repair" is a terrible phrase.  There is regeneration and repair. Regeneration replicates original structure. Repair is any response to injury short of that.  Aberrant repair then refers to repair which is disproportionate to injury.  In experimental injury, this is easily known. In clinical medicine, there is only very rarely a control group of “normal” repair. Perhaps keloid falls into that category but it hard to think of much else.  Most discussion of “aberrant” repair simply refers to failure of regeneration, not aberrant repair per se.  

Similarly, the literature is full of references to "pathologic response" when what is meant is pathologic outcome.  A pathologic outcome i.e. disease, is one in which function is reduced, even if only temporarily. A pathologic response presumably refers to any response (or process) that either 1) leads to a worse outcome than regeneration or 2) worse than is achieved under some other circumstance e.g. by others with same degree of injury.

While it would be tempting to restrict the use of "pathologic" only to examples of these intrinsically dysfunctional responses, we generally don't know at any given time whether a response is dysfunctional or not until we attempt to modify it.