Introduction to General Pathology

VPM 152 Paul Hanna DVM , M Sc, DACVP January 2016

See my website (http://people.upei.ca/hanna) for lecture powerpoints, notes, etc

I. Definitions & Terminology

Disease: (2 definitions)
1. a disorder of structure or function, especially one that produces specific clinical signs.
2. any deviation from, or interruption of, the normal structure or function of any part, organ or system of
the body; which may be clinical (characteristic set of symptoms and signs) or subclinical and whose
etiology, pathology and prognosis may be known or unknown.
(note: symptom = any indication of disease perceived by the patient and a term therefore not applicable to animals;
in veterinary medicine we use ‘clinical signs’ = observed abnormalities of structure or function) .

Pathology: (2 definitions)
1. the study of disease; literally, the study of (-logy) suffering (pathos).
2. the study of the functional, biochemical and morphological alterations in cells, tissues and organs that
underlie disease.

General Pathology: the study of the basic reactions of cells and tissues to abnormal stimuli that underlie all
diseases.

Systemic Pathology: the study of the specific responses of specialized organs and tissues to more or less well
defined pathologic stimuli.

Four aspects of a disease form the core of pathology:

Ø Etiology
C the cause of disease; genetic vs acquired (eg infectious, nutritional, chemical, physical, etc).
C many diseases are multifactorial; combination of inherited susceptibility & external influence.

Ù Pathogenesis
C the mechanisms or sequence of events leading from initiation of cell or tissue injury to disease
development.

Ú Morphologic Changes
C the structural alterations (gross or microscopic) in cells or tissues that are often characteristic of the
disease.

Û Clinical significance (functional derangements)

C the nature of the morphologic changes and their distribution in organs / tissues influence normal function
and determine the clinical signs, course and prognosis of the disease.

Lesion: any structural (or functional) abnormality in an organ, tissue or cell.

Pathognomonic: a lesion or sign that is specifically distinctive or characteristic of a disease or pathological

condition.
Gen Path (VPM 152) Introduction 2

Necropsy/Autopsy:
C postmortem examination of the body to determine the nature of pathological processes that contributed to
death or disease.
- autopsy is usually defined as examination of a human body.
- necropsy is the postmortem examination of any other animal.

Biopsy: the removal and examination of tissue from the living body to establish a precise diagnosis.

Diagnosis: a concise statement or conclusion concerning the nature, cause, or name of a disease.
(note: the accuracy of a diagnosis is limited by the evidence available for study)

Ø Differential Diagnosis (“rule-outs”):

C a list of diagnoses that could account for the history, clinical signs or lesions in a case.

Ù Clinical Diagnosis:
C diagnosis based on data obtained from the case history, clinical signs, and physical examination.

Ú Morphologic Diagnosis (lesion diagnosis):

C a diagnosis based on the predominant lesion(s) in the tissue.
C it may be macroscopic (gross) or microscopic (histologic) and describes the severity, duration, distribution,
location and nature (eg degenerative, inflammatory, neoplastic) of the lesion.
C eg severe, acute, locally-extensive, fibrinous bronchopneumonia.

Û Etiologic Diagnosis:
C a diagnosis that names the specific (or general) cause of the disease. (eg parvoviral enteritis, parasitic
hepatitis)

Ü Disease (Definitive) Diagnosis:

C a specific diagnosis that states the “name of the disease”.

eg, an 8-week old puppy presented to the veterinary clinic with severe bloody diarrhoea of 2 days duration. The
puppy died prior to complete clinical work up and a necropsy was performed.

Clinical Diagnosis......................................... Hemorrhagic diarrhea

Morphologic Diagnosis................................. Severe, acute, diffuse, necrohemorrhagic enteritis
Etiologic Diagnosis....................................... Parvoviral enteritis
Disease Diagnosis (name of the disease) ..... Canine Parvovirus

eg, necropsy of a 4 yr-old dairy cow with a history of chronic diarrhea and emaciation.

Clinical Diagnosis......................................... Chronic diarrhea

Morphologic Diagnosis................................. Severe, chronic, segmental, granulomatous enteritis
Etiologic Diagnosis....................................... Mycobacterial enteritis
Disease Diagnosis (name of the disease) ..... Johne’s Disease
Gen Path (VPM 152) Introduction 3

II. Who are Pathologists?

Ø Morphologic (anatomic) Pathologists vs Clinical Pathologists

C morphologic pathologists ! study morphologic manifestations of disease (gross, LM, EM, etc)
C clinical pathologists ! laboratory analysis of disease in living patients (cytology, hematology, chemistry, etc)

Ù Veterinary vs Medical vs Comparative Pathology

C veterinary pathologists ! mammalian, avian, zoo & wildlife, lab animal / primate, fish, etc.
C medical pathologists ! humans.
C comparative pathologists ! animal models of human disease.

Ú Diagnostic Pathology vs Experimental / Molecular Pathology vs Toxicologic Pathology

C diagnostic ! necropsy and surgical biopsies.
C experimental ! infectious, oncology, toxicologic, etc.
C molecular ! study of molecular / genetic basis of disease (PCR, RFLP, DNA sequencing, etc)
C toxicologic ! study of changes elicited by pharmacological, chemical & environmental agents.

Û Special systems pathologists

C neuropathologist, dermatopathologist, immunopathologist, etc.

III. Descriptions in Gross Pathology

1. No interpretation should appear in the descriptions of lesions.

(It is possible for a person with a good command of the language to describe perfectly a necropsy specimen,
although she/he knows nothing of its significance).

2. Description should be:

Ø Concise
Ù Grammatically correct
Ú Anatomically accurate

3. Don’t use / minimize comparative references to food (“gourmet pathology”) or sports equipment.

4. Avoid making a description based on a preconceived diagnosis (3 Steps Useful in Veterinary Medicine)
Ø OBSERVE carefully
Ù DESCRIBE completely
Ú DIAGNOSE (DEDUCE or INTERPRET) confidently
Gen Path (VPM 152) Introduction 4

5. Components of a description (not all are applicable in every case).

Ø TISSUE ....................... identify the organ or structure. Te

Ù NUMBER .................... how many lesions are present? N

Ú DISTRIBUTION .......... focal, multifocal, locally-extensive, diffuse. Di

Û SHAPE ......................... spherical, rectangular, symmetrical, etc. S

Ü COLOUR .................... no unusual color terms. C

Ý SIZE ............................ metric length, area, weight, % organ involved. S

Þ PATTERN ................... zonal, reticulated, mottled, variegated, etc Pa

ß CONSISTENCY .......... soft, firm, hard, fluctuant. Ce

à SPECIAL FEATURES.. polypoid (sessile vs pedunculated), papillated, etc.

á Other
C odor: significant and distinctive odours, eg: sweet, foul, sulphur-like, etc
C surface: smooth, rough, shiny, dull, ulcerated, undulating / wavy, bosselated, depressed, glistening, etc

6. You must know the NORMAL before you can recognize the ABNORMAL!

7. Avoid using the word "lesion" in the description. The lesion is what you are describing, ie any structural or
functional abnormality in an organ, tissue or cell.

8. Morphologic Diagnoses: may include some or all (with inflammation) of the following modifiers/qualifiers:

Ø Severity - mild, moderate, marked /severe

Ù Duration - peracute, acute, subacute, chronic, chronic-active

Ú Distribution - focal, multifocal (multifocal to coalescing), locally-extensive, diffuse, bilateral/unilateral, etc

Û Nature of the lesion

- if inflammatory, type of exudate (eg purulent, fibrinous, necrotizing, etc)
- if degeneration, type of degeneration (eg hydropic degeneration, fatty degeneration, etc).
- if neoplasia, type of neoplasia (eg carcinoma, adenocarcinoma, sarcoma, etc)

Ü Organ (prefix) + disease process (suffix)

- eg dermatitis, dermatopathy, dermatosis
- there may be an indicator of a particular subcompartment of an organ being affected, eg, nephritis vs
interstitial nephritis or glomerulonephritis or pyelonephritis.
Gen Path (VPM 152) Introduction 5

Disease Suffixes

Ø ORGAN + OPATHY (disease of an organ; often used when the etiology / pathogenesis is not entirely clear).
C eg Hepatopathy - disease of the liver, esp when etiology / pathogenesis unclear.
Nephropathy - disease of the kidney, esp when etiology / pathogenesis unclear.

Ù ORGAN + OSIS (noninflammatory disease of an organ, often used if degeneration / necrosis)

C eg Hepatosis - disease of the liver, esp when degeneration &/or necrosis of hepatocytes.
Nephrosis - disease of the kidney, esp when degeneration &/or necrosis of kidney (esp tubules).

Ú ORGAN + ITIS (an inflammatory disease of the organ).

C eg Hepatitis - inflammation of the liver.
Nephritis - inflammation of the kidney.

Classification of Inflammatory Lesions (modified from Mechanisms of Disease, Slauson & Cooper, 2002)

Severity Duration Distribution Exudate Anatomic Organ

Modifiers
Minimal Peracute Focal Suppurative / Interstitial, Nephritis
purulent Glomerulo-,
Pyelo-
Mild Acute Multifocal Fibrinous, Portal Hepatitis
(+/- multifocal to coalescing) Fibrinopurulent
Moderate Subacute Locally-extensive Necrotizing, Transmural Enteritis
(segmental*) necrosuppurative
Marked or Chronic Diffuse Granulomatous Embolic, **Pneumonia
Severe Interstitial,
Broncho-
Chronic-active Hemorrhagic Encephalitis
*note: segmental is often used for a locally-extensive lesion in a tubular organ (eg segmental enteritis, segmental metritis, etc)
**note: pneumonia is the term typically used for inflammation of the lung, not "pneumonitis"
pleuropneumonia is the term for inflammation of the pleura and lungs, not "pleuropneumonitis"

C eg’s of morphologic diagnoses:

- Multiple compound (open) fractures of the left femur
- Moderate, diffuse, bilateral, adrenal cortical hyperplasia
- Mild left ventricular hypertrophy
- Squamous cell carcinoma of the pinna
- Multicentric lymphoma
- Moderate, acute, multifocal, necrotizing, hepatitis (= Hepatitis, necrotizing, multifocal, acute, moderate)
- Severe, chronic, focal, ulcerative, dermatitis (= Dermatitis, ulcerative, focal, chronic, severe)
- Severe diffuse bilateral nephrosis
Gen Path (VPM 152) Introduction 6

(From Slauson and Cooper, Mechanisms of Disease, 3 rd ed, 2002)

Gen Path (VPM 152) Introduction 7

IV. PRACTICAL INFORMATION ABOUT HISTOLOGIC STAINS

1. Classes of biologic stains:

a. General tissue stain
C Hematoxylin and Eosin (H&E) is the standard stain used for histopathology.
- the nucleus stains blue (hematoxylin) and the cytoplasm stains red (eosin).
b. Histochemical stains (“special stains”)
C a variety of histochemical stains are available for more refined identification of cell types, intracellular
components and extracellular materials (see table below).
c. Immunohistochemistry
C now a routine tool in veterinary pathology, used to identify a variety of microbial and cellular (esp tumor)
antigens.

Commonly Used Histochemical Stains *for reference*

TYPE OF STAIN SPECIAL USE

Hematoxylin & Eosin (H&E) standard stain used in routine histopathology

Oil-Red-O (on frozen sections) lipid

Toluidine Blue mast cell granules

Phosphotungstic acid-haematoxylin (PTAH) fibrin, cross striations of skeletal muscle fibers

Masson's trichrome connective tissue, collagen

Alcian blue mucins (glycosaminoglycans / proteoglycans)

Periodic acid-Schiff (PAS) glycogen, fungi

Congo Red amyloid

Gram Stain (Gram-Twort method) bacteria

Gomori Methenamine Silver (GMS) fungi

Von Kossa calcium salts

Perl’s Prussian blue iron

Luxol Fast Blue (LFB) myelin

Acid fast stain mycobacterial organisms & other acid fast + organisms

Fontana Masson's melanin and argentaffin cells

Reticulin silver reticulin fibers

Verhoeff - Van Gieson (VVG) elastic fibers

V. STUDENTS VISITING POSTMORTEM ROOM

C you are welcome to visit (space permitting), but when you do, you must comply with the following:
Ø wear one of the labcoats hanging at the entry (not your blue coats which you wear throughout the building)
Ù wear rubber boots or plastic coverings (again provided at the entry) with pants tucked in
Ú if you are there to participate in a necropsy, coveralls must be worn
Û please wash your hands and boots thoroughly before leaving the lab