Imagine the Biochemistryland map lying flat on the ta- ble. There are other maps in medicine that may be stacked on top of Biochemistryland at increasingly higher hierarchical levels (fig. 1l.1). These include Cell Biolo- gyland, Histologyland, Anatomyland, and the realm of the Individual and Society. At the bottom, Biochemistry- land, there are chemical reactions that interconnect exten- sively with one another. The chemical reaction arrows at this level are not, only the arrows on our own Bio- chemistryland map but all the additional feedback arrows from reaction products, hormones, and other molecules not shown on the map. Biochemistryland really resembles a giant spider web, or system of rivers, in which motion at any point can cause changes throughout much of the system. #1 | | |
There are also connections within each of the higher level maps. Changes within organelles can affect other organelles in Cell Biologyland: defective mitochondria, for instance, may affect other organelle functions . In His- tologyland, changes of certain cell types can affect the function of other cell types: for example, a loss of sub- stantia nigra nerve cells in the brain stem may lead to the degeneration of basal ganglia cells on which they nor- mally connect. In Anatomyland, malfunction of one or- gan system can affect others: inadequate pulmonary function will affect the functioning of the heart and other organs. Interactions between individuals can affect soci- etal functioning. #2 | | |
It is also true that each of the hierarachical levels inter- acts with one other. For instance, abnormalities of bio- chemical reactions can affect the functioning of select #3 | | |
organs; hypoglycemia, for instance, may result in coma. Emotional stress can precipitate heart attacks, gastric hy- peracidity, epinephrine production, etc., inducing changes all the way down to the biochemical level. Con- versely, mood-altering drugs that act at the biochemical level can affect the functioning of the individual and the individual's interactions with society. #4 | | |
.In medicine, we unknowingly continually shift between levels in working with different clinical conditions. We have seen a number of diseases scattered through Bio- chemistryland, but these are for the most part.rare, Cell Biologyland contains..cytokines, protein hormones that help regulate cell interactions in such important areas as the immune response, wound healing, and carcinogene- sis. Cell Biologyland also contains myopathies that affect mitochondria, and there are lysosomal storage diseases, but these are uncommon. Clinical thinking in large part centers on higher levels. Histologyland has a great deal of tumor pathology. Anatomyland has an enormous bulk of clinical disorders related to organ pathology-the he-art attacks, fractures, muscle spasms, strokes , liver and kid- ney diseases, etc. Levels of the individual and society contain many psychiatric and sociopathic disorders. #5 | | |
Thinking at different levels brings out additional infor- mation; new concepts of function arise on ascending through the hierarchy, just as a particular arrangement of bricks becomes something new-a "house" . The concept of an organ is not ingrained in any particular reaction in Biochemistryland but in the integration of many complex reactions that forms something new, an organ. If my car door gets smashed in, I could go to the body shop and ask for a particular combination of metal alloys, arranged as #6 | | |
so many kinds of molecules packed together into a space of such an'! such dimensions. More appropriately, how- ever, I will simply ask for a new car door, the "door" being the unit to focus on rather than the molecules that compose the door. Similarly, particular clinical disorders are best thought of as occurring at certain levels; when one deals with a lacerated liver, one is not going to think of the replacement and apposition of certain kinds and number of molecules that constitute liver cells; one is going to think in terms of surgical techniques that repair a lacerated liver. Even though everything can ultimately re- duce itself to biochemistry, working at a particular hierar- chical level can provide a better way ofthinking about the same material. #7 | | |
While it is often more practical to think at a particular heirarchical level, it is important not to get so fixated at anyone particular level as to ignore the effects one level may have on another, as if they were separate and unre- lated realms. One must remember that the individual lev- els interconnect. Higher level personal-social situations can affect one's biochemistry, and biochemical changes can affect one's personal-social status. Things like bed- side manner, hope, and the placebo effect can have real effects on underlying biochemistry, just as biochemical changes can affect mood and behavior. #8 | | |
It is better, where possible, to treat the root cause of an illness rather than a peripheral manifestation of the ill- ness. When one treats just the manifestation, one may eliminate it, but this does not eliminate the many other
widespread changes that the original illness may have
caused throughout the heirarchy oflands. Ifa depression is situationally induced, it is better, where possible, to correct it at the higher situational level than to deal with it through medication at the lower biochemical level; the originating problem otherwise persists and there may be medication side effects. Thoughts such as these may ap- pear obvious. No one would think of trying to treat a heart attack by lowering elevated blood levels of CPK enzyme that leaked out of the damaged cardiac cells. In . other situations the logic is less clear. Thus, there have been and still are controversies over whether lowering blood levels of cholesterol in hypercholesterolemia, or glucose in diabetes has a significant effect in preventing atherosclerosis. Do such clinical measures get at root causes, and ifthey do not, do such measures significantly affect the course of disease? #9 | | |
There are many medical conditions for which a root cause is unknown and one has to focus on treating periph- eral manifestations (e.g., treating inflanunation in arthri- tis with antiinflammatory drugs). Even when a root cause is known. it may be difficult to treat if the problem is localized to a particular area of the body; the medication may not only affect me problem area in the body but have side effects on other regions-for example, the side ef- fects of antitumor a~ents on normal cells. When the root cause is outside the body, e.g., smoking as a cause of lung cancer, elimination of the root cause can be both feasible and clinically effective. Hence, the importance of Preventive Medicine as an important influence on the hi- erarchical schema. #10 | | |
