Applying the Basic Sciences to Clinical Medicine
Pathology is best learned by a systematic approach, first by learning the language of the discipline and then by understanding the function of the various processes. Increasingly, the understanding of cell and organ function plays an important role in the understanding of disease processes and the treatment of disease. Initially, some of the "language" must be memorized in the same way that the alphabet must be learned by rote; however, the appreciation of the way the "pathology words" are constructed requires an understanding of mechanisms, in essence, an awareness of "how things are put together and work together."
Physicians usually approach clinical situations by taking a history (asking questions), performing a physical examination, obtaining selected laboratory and imaging tests, and then formulating a diagnosis. The conglomeration of the history, physical examination, and laboratory tests is called the clinical database. After a diagnosis has been reached, a treatment plan usually is initiated, and the patient is followed for a clinical response. Rational understanding of disease and plans for treatment are best acquired by learning about the normal human processes on a basic science level, and likewise, being aware of how disease alters the normal physiologic processes is understood on a basic science level. In short, clinical problem solving involves three basic steps: (1) making a diagnosis, (2) initiating a therapy, and (3) monitoring the patient's response.
There are seven key questions that help to stimulate the application of basic science information to the clinical setting.
1. Given histologic findings in an organ, what are the most likely clinical manifestations?
2. Given clinical symptoms, if a tissue biopsy is taken, what histologic findings are most likely to be seen?
3. Given clinical findings, if the microscopic photograph is shown, what is the most likely diagnosis?
4. Given a histologic description, what would be the most likely complication to the organ in question?
5. Given a gross description of a pathologic lesion, what is the most likely diagnosis?
6. Given autopsy findings, what is the most likely diagnosis?
7. Given histologic findings, what is the most likely explanation?
1. Given histologic findings in an organ, what are the most likely clinical manifestations?
This is a fundamental principle in the understanding of the discipline of pathology. The student first must understand the normal histologic structure in an organ in the context of its function. Then the student must be able to relate the abnormal histology to clinical findings, both subjective (patient complaints) and objective (physical examination findings). The organ or system is highly organized both on the gross and on the microscopic level. There also must be awareness of the mechanism that causes disruption of the normal cellular architecture.
2. Given clinical symptoms, if a tissue biopsy is taken, what histologic findings are most likely to be seen?
This is the converse of the first question and requires going backward from clinical manifestations to the probable disease process to probable histologic findings. The student must be able to translate the clinical picture to the cellular characteristics. This also requires being aware of what symptoms various cellular alterations will produce in the patient; for instance, some changes will be silent and not cause symptoms, whereas other changes will produce dramatic manifestations.
3. Given clinical findings, if the microscopic photograph is shown, what is the most likely diagnosis?
This sequence of analysis is very similar to the practice of "real-life" medicine, the role of the pathologist. The clinical history and physical examination are critical to putting the pathologic findings into context. For instance, if endometrial curettings are sent to the pathologist and on microscopy reveal crowded, complex glands, abnormal epithelial nuclei, and loss of nuclear polarity, the pathologist may render a diagnosis of cancer. However, when the information is given that the patient is 6 weeks pregnant, the diagnosis of an Arias-Stella reaction is made, an expected finding in the endometrium in light of the human chorionic gonadotropin levels of pregnancy. The next logical step is to propose a treatment. Thus, the student should be able to shift back and forth between the basic science and the clinical areas:
Pathophysiology « Histologic Findings « Diagnoisis « Treatment
4. Given a histologic description, what would be the most likely complication to the organ in question?
This analysis requires that the student be able to relate the histologic findings of one organ to a disease process and then extrapolate the probable changes to another organ. The student should become proficient at working back and forth between histologic changes and clinical findings and disease processes. The best way to acquire this skill is to think in terms of mechanisms of disease and not just memorize key words. It is the understanding of the underlying pathophysiology of the disease that allows the physician-scientist to make rational predictions of the natural history of a disease process.
5. Given a gross description of a pathologic lesion, what is the most likely diagnosis?
The student of pathology also must be able to process the visual picture of the organ, biopsy specimen, or cytology, as well as the written description. Because the pathologist often communicates with clinicians by using written reports, the student should be able to take the written description and apply that information to the clinical setting, such as making a diagnosis. For instance, if the description is that of an ovarian cyst with sebaceous material, hair, and teeth, the most likely diagnosis is a benign cystic teratoma.
6. Given autopsy findings, what is the most likely diagnosis?
This question is similar to the analysis performed by working back from gross pathologic description to the diagnosis. In cases of a patient's death, an autopsy often will be helpful in explaining the circumstances surrounding the death, or the etiology. The student of pathology must be able to correlate the postmortem examination with the probable diagnosis and be able to speculate about the interaction between disease and host. For example, the case may involve a 30-year-old female who suddenly collapses and dies, and the autopsy reveals a dilated aortic root and aortic dissection; other findings include long extremities and long fingers. The most likely diagnosis is Marfan syndrome.
7. Given histologic findings, what is the most likely explanation?
The student once again is challenged to relate the histologic findings in the context of scientific explanation and not just memorize the histologic findings of a certain disease. For example, the histologic specimen may reveal a pulmonary lesion with an area of central necrosis surrounded by epitheliod and multinucleated giant cells. The explanation would be that the organism is probably Mycobacterium tuberculae, which evades phagocytosis from macrophages because it has complement C3b antigen on its cell wall. It is incorporated into the macrophage, and the tuberculosis bacterium blocks fusion of the lysosome with the phagosome, allowing the bacterium to multiply within the macrophage. The responding T cells produce cytokines such as interferon type II (IF-2) to activate other T cells and interferon gamma (IFN-gamma), which activates macrophages, transforming them into epitheloid cells and multinucleated giant cells. Thus, it is delayed or cell-mediated immunity that is required to address the infection. The monocyte response, dictated by the type IV hypersensitivity reaction of cell-mediated immunity, leads to the caseous necrosis (acellular debris in the center), as well as the granulomatous reaction. The cell-mediated immune response also explains the need to wait 48 to 72 hours for a skin response to the purified protein derivative (PPD) test to assess for prior exposure (sensitivity) to tuberculosis.
PATHOLOGY PEARLS
· There are seven key questions to stimulate the application of basic science information to the clinical arena.
· Medicine is both an art and a science.
· The scientific aspect of medicine seeks to gather data in an objective manner, understand physiologic and pathologic processes in light of scientific information, and propose rational explanations.
· A skilled clinician must be able to translate back and forth between the basic sciences and the clinical sciences.
REFERENCES
Kumar V, Abbas AK, Fausto N. Acute and chronic inflammation. In: Robbins and Cotran pathologic basis of disease, 7th ed. Philadelphia: Elsevier Saunders, 2005:48-83.
Mark DB. Decision making in medicine. In: Kasper DL, Fauci AS, Longo DL, et al., eds. Harrison's principles of internal medicine, 16th ed. New York: McGraw-Hill, 2004:6-13.
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