2. OBJECTIVES
Understand the 3 main anatomic concepts of
disease---Degenerative, Inflammatory,
Neoplastic
Understand the concepts of cellular growth
adaptations---Hyperplasia, Hypertrophy,
Atrophy, Metaplasia
Understand the factors of cell injury and
death---O2, Physical, Chemical, Infection,
Immunologic, Genetic, Nutritional
3. OBJECTIVES Understand the pathologic mechanisms at
the SUB-cellular level---ATP,
Mitochondria, Ca++, Free Radicals,
Membranes
Understand and differentiate the concepts
of APOPTOSIS and NECROSIS
Understand SUB-cellular responses to
injury---Lysosomes, Smooth endoplasmic
reticulum, Mitochondria, Cytoskeleton
4. OBJECTIVES
Identify common INTRA-cellular
accumulations---Fat, Hyaline, CA+
+, Proteins, Glycogen, Pigments
Understand aging and differentiate
the concepts of preprogrammed
death versus wear and tear.
11. Most long term students of pathology, like
myself, will strongly agree that the very best
way for most minds to remember, or identify,
or understand a disease is to associate it with
a morphologic IMAGE.
This can be gross, electron microscopic, light
microscopic, radiologic, or molecular.
In MOST cases it is at the LIGHT
MICROSCOPIC LEVEL.
22. METAPLASIA
• A SUBSTITUTION of one NORMAL
CELL or TISSUE type, for
ANOTHER
–COLUMNAR SQUAMOUS (Cervix)
–SQUAMOUS COLUMNAR
(Glandular) (Stomach)
–FIBROUS BONE
–WHY?
23. CELL DEATH
• APOPTOSIS vs. NECROSIS
• What is DEATH? (What is LIFE?)
–DEATH is IRREVERSIBLE
24. So the question is….
…NOT what is life or
death, but what is
REVERSIBLE or
IRREVERSIBLE injury
70. PIGMENTS
EX-ogenous--- (tattoo, Anthracosis)
END-ogenous--- they all look the
same, (e.g., hemosiderin, melanin,
lipofucsin, bile), in that hey are all
golden yellowish brown on “routine”
Hematoxylin & Eosin (H&E) stains
74. CALCIFICATION
•DYSTROPHIC (LOCAL
CAUSES) (often with FIBROSIS)
•METASTATIC (SYSTEMIC
CAUSES)
–HYPERPARATHYROIDISM
–“METASTATIC*” Disease
*NOT to be confused with “metastatic” calcification
75. CELL AGING parallels
ORGANISMAL AGING
PROGRAMMED THEORY (80%)
vs.
WEAR AND TEAR THEORY (20%)
Editor's Notes
These are the four aspects about every disease you should keep in mind as a knee jerk reflex every time you hear the name of a disease
Know the definitions of all these terms, for the rest of your life, even if it is only from the dictionary. Most are cellular/tissue reactions to injury.
Hyperplasia is an increase of the size or weight of an organ or tissue due to increased NUMBERS of cells. Hypoplasia is the opposite.
Hypertrophy is increase in the size (weight) of an organ or tissue due to increase of the size of the cells. Hypotrophy (more commonly called atrophy) is the opposite. There are many common violations to this concept.
The precise differentiation between cell life and cell death is about as controversial as human life or human death.
These are three indisputable reversible changes
These are three indisputable IR-reversible changes
The usual suspects are always suspected in carcinogenesis, teratogenesis, inflammations, or, really, any disease in general.
So just as you always tend to think of diseases as inflammatory, neoplastic, degenerative, you should always think of causes as physical, chemical, and infectious.
Death is easier to define than life. These two definitions of cell death are indisputable. The best definition of life is not death, in all honesty.
The closer we look at something, the easier it is to tell if it is dead, alive, or dying.
In light microscopy inability to recognize nuclei because they broke up (karyorhexis, karyolysis) is a common criterion of cell death.
On routine gross or microscopic examination “necrosis” is used as synonymous with cell or tissue death. These are not really good terms but have been used as common adjectives over the ages. If you want to convince somebody you are a Nobel prize winning Prussian pathologist, you can pronounce the word as neg-ROW-zeese
When the brain tissue dies it tends to soften, then liquefy, so there can be more water (i.e., protons) to cause increased MRI signals.
T2 weighted MRI images emphasize water density but some anatomic resolution is lost.
“Caseous” means “cheese-like” this is a GROSS observation, not a microscopic one. Cheese has less texture than meat, and is flaky. Many people from Wisconsin have been called caseous, i.e., cheeseheads.
Fibrinoid necrosis looks like fibrin microscopically. In fact, often, it is fibrin.
Wet gangrene comes BEFORE dry gangrene. Why? Gangrene is also a type of necrosis, and the term “gangrenous necrosis” is common.
Dry gangrene is deader, i.e., longer standing, than the death of wet gangrene.
In reperfusion injury, damage occurs AFTER the oxygen, or blood, is restored! Chemical injury can be DIRECT, or INDIRECT, if the chemical is converted into a toxic metabolite.
An infarct is defined as “dead tissue” due to lack of blood flow, and therefore lack of oxygen, nutrients, etc.
The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane (Wikipedia definition)
As in pharmacology, EVERY chemical can be toxic, even pure water, so its always a question of dosage.
Apoptosis come from the Greek word which means “falling off”.
Cells which have shorter life spans are subject to apoptosis.
There is often a grey area between apoptosis and necrosis, especially in the area of “pathologic”, rather than normal, apoptosis.
Nuclei get smaller, “darker”, then fragment, then dissolve. What is the correct name for EACH of these 4 processes?
Shrinkage (pyknosis), increased nuclear staining (hyperchromasia), nuclear fragmentation (karyorrhexis, karryolysis), are classic features of apoptosis.
The two main cell which clean up dead cell fragments are macrophages (also called “histiocytes”) and neutrophils.
Caspases, or cysteine-aspartic proteases, are a family of cysteine proteases, which play essential roles in apoptosis (programmed cell death), necrosis and inflammation. http://en.wikipedia.org/wiki/Caspases
The term “hyaline” is the most commonly confused concept in pathology. ANY eosinophilic staining, amorphic substance, can be correctly called hyaline, especially necrosis, amyloid, various proteinaceous secretions, fibrin are the most common.
Name the three most common causes of fatty liver: Ans: diabetes, obesity, alcoholism (toxic)
Sometimes the terms MICROvesicular versus MACROvesicular steatosis is used dependong whether the fat droplets are smaller or bigger than a cell. Sometime the term “fatty change” is also used.
The slit-like spaces are cholesterol clefts, a classic feature of atherosclerosis.
If you see a golden brown, slightly refractile pigment on routing light H&E microscopy, it is either hemosiderin, melanin, or bile derived. A few other degenerative pigments, such as lipofucsin, are also possible. Special stains can prove it is one or the other, if it is not abundantly clear from its cellular or pathologic setting and/or location
This tiny amount of microscopic tattoo pigment can make white skin look quite black! Is this EXogenous or ENDogenous?
Why does anthracosis look worse along the pleural surface than on cut sections?
Why are MANY extrathoracic lymph nodes also anthracotic?
What in the body is black and NOT due to EXOGENOUS pigments?
Why would somebody order a prussian blue stain, or a S-100 immunoperoxidase stain or a HMB-45 stain?
Calcium stains deep blue (very basophilic) and crunchy in all settings.
