Pathologic Basis of Clinical Medicine

Question 1

Lo #1: Understand the role of pathology in prevention, diagnosis, treatment, and management of disease.

Answer 1

Pathology is a medical specialty that involves the study and diagnosis of disease through examination/analysis of a wide variety of patient specimens, including
organs removed during surgery, tissue biopsies, blood, sputum, feces, other body fluids (urine, peritoneal fluid, synovial fluid, pleural fluid, cerebrospinal fluid)
and even the entire body during post-mortem examination (autopsy). Through examination of these specimens, the pathologist provides pivotal information for prevention, diagnosis, treatment and management of disease.

Question 2

LO #2: Describe the basic mechanisms of disease

Answer 2

a. Cell Injury, cell death and adaptations – cells encounter many stresses due to changes in their internal and external environments. If an injury exceeds the
cells ability to adapt, the cell will die. Causes of cellular injury are many, including:
i. Hypoxia (lack of oxygen)
ii. Pathogens (viruses, bacteria, parasites, fungi, prions)
iii. Immunologic dysfuction (hypersensitivity, autoimmune)
iv. Inherited mutations
v. Chemical injury (drugs, poisons, occupational exposures, alcohol,
tobacco, etc)
vi. Physical injury (trauma, burns, frostbite)
vii. Nutritional or vitamin imbalance
Cellular responses to injury include adaptation (hypertrophy, atrophy,
hyperplasia, metaplasia), reversible injury, and irreversible injury and cell
death (necrosis, apoptosis).

b. Inflammation and repair – Inflammation is a reaction of tissue to an injurious agent (pathogens, damaged tissue) which facilitates entry of inflammatory cells, plasma proteins and fluid to the site of injury. Inflammation involves vascular responses, migration and activation of leukocytes and systemic reaction. Acute inflammation is an immediate response (minutes to days) to
infection (to eliminate pathogen) or injury (to clear dead cells). The keyplayers of which are vascular changes, chemical mediators, and neutrophils. Chronic inflammation is a delayed response to persistent infection (most common cause), infection with certain organisms (viruses, mycobacteria,
parasites, fungi), autoimmune disease, foreign material (sutures), and some cancers. Repair of damaged tissues is initiated when inflammation begins. This
process involves hemostasis (coagulation, platelets), inflammatory cells, regeneration of cells (if possible), fibrosis, and remodeling.

c. Hemodynamic disorders, thromboembolism and shock – the health of tissues depends on circulation of blood, which delivers oxygen and nutrients and removes waste. This exchange typically occurs in the capillary beds, where there is little net movement of water and electrolytes into the tissues. When this balance is lost and fluid accumulates in the tissues, we call this edema.
Blood vessels may be damaged during trauma, hemostasis, or blood clotting, is the process that prevents excessive bleeding after injury to a
vessel. If hemostasis is inadequate, excessive bleeding or hemorrhage may ensue. If hemorrhage is massive and rapid, it may lead to hypotension and shock. On the other hand, if clotting is excessive (thrombosis) or a portion of a blood clot migrates (embolism), a blood vessel may be occluded, impairing delivery to the tissue (ischemia, infarction).

d. Diseases of the immune system – defects in the immune system (immunodeficiency diseases) can lead to increased susceptibility to infections. The immune system can also cause tissue injury and disease
through immune reactions that cause injury (hypersensitivity reactions). In autoimmune disorders, there is failure of tolerance to self-antigens and the
immune system response is directed against self antigens.

e. Neoplasia – new tissue growth that is unregulated, irreversible and monoclonal (neoplastic cells derived from a single cell). Include benign and
malignant neoplasms.

f. Genetics and Pediatric diseases – genetic abnormalities (mutations, amplifications, deletions, translocations, etc) that affect the structure and
function of proteins, disrupt cellular homeostasis and cause disease.

g. Environmental and nutritional diseases. Environmental diseases are caused by environmental factors. Include exposure to chemical or physical agents in
the environment: climate change, tobacco, alcohol, drugs (therapeutic and drugs of abuse), physical agents (mechanical trauma, thermal injury,
electrical injury, radiation), and nutritional diseases (malnutrition, vitamin deficiencies, obesity, anorexia nervosa and bulimia).

Question 3

LO #3: Describe the three basic competencies in pathology

Answer 3

1) Understand core principles of disease mechanisms/processes (general
pathology) such as cell injury, inflammation, tissue repair, vascular damage and response, mutations, neoplasia, and infection.

2) Apply knowledge of disease mechanisms to organ systems and become familiar with the epidemiology, pathologic features (gross and microscopic),
and diagnostic techniques of common disorders. In addition, the clinical presentation, natural history of the disease if untreated, and likely outcome
when treated, should be known.

3) Apply general and system pathology to diagnostic medicine. When signs and symptoms derived from history and physical examination are insufficient to
make a diagnosis, what laboratory or imaging studies are indicated? Demonstrate effective utilization of laboratory testing and imaging studies

Question 4

LO #4: Describe the approach used in the diagnosis of neoplasms and other pathologies, including the use of tumor markers.

Answer 4

Microscopic Examination (histologic and cytologic methods) -

Several sampling approaches are available, including

1) excision or biopsy,
2) fine needle aspiration
3) cytologic smears (ex: cervical Pap smear).

The tissue must be adequate (don’t be stingy!), representative of the lesion and properly
handled/preserved. A pathologist evaluates the histologic features to determine the nature of the lesion (benign or malignant), the cell/tissue of origin, and other
prognostic features (grade, stage, margins etc.). In some instances, the cell/tissue of origin of a neoplasm is not apparent from routine H&E histology; in these cases, other methods are used to determine the origin of the neoplasm (immunohistochemical stains, flow cytometry, molecular/genetic, see below).

Ancillary Techniques: Include electron microscopy, flow cytometry, molecular/genetic testing, and immunofluorescence.

Molecular/Genetic Testing – An increasing number of techniques are readily available and being used in routine clinical practice for the diagnosis of tumors,
prognosis, therapeutic decisions, and to determine response to treatment. Commonly used techniques include karyotypic analysis, PCR and FISH
(Fluorescence in situ hybridization). More recently, next generation sequencing and
microarrays have gained wider application and availability.

Tumor Markers – Substances produced by tumors (tumor-associated enzymes,
hormones, and other tumor markers) can be identified in the blood or other body
fluid. These substances are useful in several ways: tumor screening, diagnosis,
prognostic indicators and monitoring the outcome of therapy (monitoring for
relapse). They are not used for a definitive diagnosis of cancer. See Table 7-12
in Robbins, 9th ed.
Examples:
1) Prostate specific antigen – prostate carcinoma, may also be elevated in
benign prostate conditions. May be useful in monitoring patients with
prostate cancer undergoing therapy – monitor for relapse
2) Carcinoembryonic antigen (CEA) – Elevated in a variety of cancers
(nonspecific): carcinomas of the colon, pancreas, lung and stomach. May
also be elevated in benign conditions, and therefore, lacks sensitivity for
the detection of early cancers.
3) Alpha-fetoprotein – cancers of liver and gonads; also elevated in benign
states including pregnancy.
4) Immunoglobulins – plasma cell neoplasms

Question 5

angiogenesis

Answer 5

formation of new vessels

Question 6

fibrosis

Answer 6

scarring

Question 7

thrombosis

Answer 7

clotting

Question 8

embolism

Answer 8

portion of clot migrates

Question 9

ischemia

Answer 9

lack of blood flow

Question 10

infarction

Answer 10

death of local tissue due to lack of blood flow

Question 11

immunodeficiency diseases

Answer 11

increased susceptibility to infections inherited or acquired

Question 12

hypersensitivity reactions

Answer 12

immune reactions that cause tissue injury

Question 13

autoimmune disorders

Answer 13

failure of tolerance to self antigens and immune response is directed against self antigens

Question 14

monoclonal

Answer 14

derived from single cell

Question 15

neoplasia

Answer 15

new growth