Now, That’s What I Call High-Yield: Pathology
- Aug 21, 2018
Sweet, sweet pathology. It’s what makes the Step 1 world go round. On the USMLE Step 1 content breakdown, we find that 55-60% of Step 1 questions are about “Abnormal processes,” so it pays to have a firm grasp of the basics of pathology. That is not to say that the terse 22-page section of First Aid will cover over half the test, but instead, that the better you can understand and articulate pathology and inflammation, the easier your studying and retainment will be.
Let’s have a look, shall we?
Necrosis is death…how morbid! But how many different kinds can there be? Let us count the ways:
Coagulative is your most common necrosis, in which the cell architecture stays maintained, but the cells contained therein are dead. Under the microscope, everything turns a bit pinker as it binds eosin (like eosinophils, the cell line that sucks up the stain).
Liquefactive necrosis occurs in the brain and in abscesses, in which cavities are formed. Cellular architecture breaks down, leaving some goo behind in its place.
Caseous necrosis forms a “cheesy” breakdown product,and usually occurs from TB or fungi. Think granulomas!
Fat necrosis classically occurs in the pancreas as saponification (soap-ifying) of fat or in the breast after trauma to the tissue.
Fibrinoid necrosis necrosis usually points to autoimmune injury to blood vessels.
Ischemia is bad for business. Like most things in the universe, all of the processes in the body depend on balance. This is especially true for oxygen balance in the entirety of the body’s tissues. Oxygen is supplied by the air we breathe, diffuses across pneumocytes in the lungs, and gets delivered to thirsty body tissues either carried by hemoglobin, or dissolved directly in the blood stream. A tissue’s oxygen demand is the sum of its basal demand plus any extra demand we ask of them. This is perhaps most clinically important in the heart. Increases in oxygen demand, such as those caused by an increase in heart rate, contractility, or afterload, can throw things out of balance and lead to ischemia. The same holds true for decreases in supply (think diseased coronaries, hypotension/decreased perfusion, severe anemia, or very poor lung function). If enough cell death occurs without revascularization, this ischemic tissue can then infarct (DIE!), leading to scarred, useless tissue. It’s basic, but a systematic approach to ischemia in general will be useful to revisit in your approach to USMLE questions.
It’s also important to know areas of organs prone to ischemia, because of a tight balance of oxygen supply and demand. These include the hippocampus, renal medulla, watershed areas of the colon (e.g., splenic flexure), and watershed areas of the brain (those most distally perfused by the major arteries).
After enough time in the hospital, the idea of inflammation becomes quite rote, and is a popular buzzword, especially in explaining disease processes to patients. Everyone has a general idea of what it is, but as a fledgling doctor, it’s necessary to have a complete understanding, all the way from the cellular level to the systemic level. Be familiar with the classic rubor, tumor, dolor, and loss of function signs. Systemic symptoms fulfill the SIRS criteria (increased/decreased temperature, increased heart rate, increased/decreased WBC, and increased respiratory rate). These changes are usually driven by another favorite buzzword, cytokines. Think IL-1, IL-6, and TNF-É‘.
What actual changes are driven by these chemical messengers? They lead to vasodilation and increased vascular permeability. With breakdown in vascular barriers, white blood cells can get where they need to go to fight infection, but edema will form in said areas. They increase body temperature and metabolic demand, which necessitates an increase in heart rate and cardiac output.
When you think of granulomas, think of chronic inflammation. As their name indicates, they are granule-like bodies that have a very specific formation pattern, very testable on Step 1. Th1 cells secrete IFN-ð², which goes on to activate macrophages. These activated macrophages then secrete TNF-É‘ forming a walled off area of chronic inflammation called a granuloma. Granulomas are important aberrant cellular structures in many clinical diseases. Some of your most high-yield examples are sarcoidosis, Crohn’s disease, granulomatosis with polyangiitis (Wegener’s disease), temporal arteritis, and of course, tuberculosis.
The difference between transudates and exudates is one of the most classical medical lessons. Now before you shout “Light’s criteria,” let’s make sure we understand the drivers of these effusions. Transudates are what’s left after plasma works its way through a capillary layer because of pressure, either increased hydrostatic (driving) pressure, or decreased oncotic (withholding) pressure. Think of transudative effusions as arising from blood being pressurized through a sieve, where only the liquid/plasma fraction gets through. That’s why they have low protein and low LDH. They will also occur if production of interstitial fluid in the lung outpaces lymphatic absorption (i.e., fluid overload). The main drivers here are you -osis’s: cirrhosis, nephrosis, and cardiosis (cute, mnemonic made up word for heart failure).
Exudative effusions occur from inflammation or malignancy breaking down the endothelial barrier entirely, allowing a more complete passage of protein and LDH across the capillaries. Ergo, they have high protein and LDH counts on analysis. Pneumonia and cancer take the cake here.
Paraneoplastic syndromes (7.5)
It seems like nowadays, these syndromes are becoming more testable than the neoplasms that cause them! Lung cancer is definitely one of the biggest offenders, and the paraneoplastic syndrome can often point to the type of cancer. Small cell lung cancer leads to SIADH, Cushing’s syndrome (from increased ACTH), and Lambert-Eaton myasthenic syndrome. Hypercalcemia due to PTHrP comes from squamous cell carcinoma of the lung. A final unforgettable connection is that between myasthenia gravis and thymoma. Don’t find one without looking for the other.
Tumor markers (7)
Knowledge of these markers is essential both for Step 1 and for the rest of your medical career. Be ready for this lot, which you’ll see most often. Sadly, no brilliant way to remember them other than spaced repetition.. Alk Phos from bone breakdown in Paget’s disease, alpha-fetoprotein from hepatocellular carcinoma, hCG from germ cell tumors and gestational trophoblastic disease CA 19-9 for pancreatic cancer, CA 125 from ovarian cancer, CEA for colon cancer, and PSA from the prostate. Remember, these are all simply associations, not causative factors or necessary screening tests. Many of the tests are used to gauge treatment effectiveness, not for detection of the disease. And some are normally elevated in certain non-tumor states, like PSA elevated in prostatitis, and hCG in a normal pregnancy.
To wrap it all up, memory of all the minutae of pathology is not nearly as important as using a foundation in the subject to further understand your system specific pathophysiology. In the end, it all breaks down to basics.