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Introduction of Pathology
DR. MUHAMMAD MUDASSAR
MBBS., FCPS ( HISTOPATH )
HEAD PATHOLOGY DEPT & ASST.
PROFESSOR
BMC, KSA
Pathology
 Pathos---suffering
 Logos---- study
 Study of suffering or
disease
 A bridging science
PATHOLOGY
GENERAL
SYSTEMIC
PATHOLOGY
ETIOLOGY (“Cause”)
PATHOGENESIS
(“Insidious
development”)
MORPHOLOGY
(ABNORMAL
ANATOMY)
CLINICAL EXPRESSION
ETIOLOGY
Cause
vs.
Risk Factors
PATHOGENESIS
“sequence of events
from the initial
stimulus to the
ultimate expression
of the disease”
MORPHOLOGY
Abnormal
Anatomy
Gross
Microscopic
Radiologic
Molecular
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.
LIGHT
MICROSCOPIC LEVEL.
In MOST cases it is at the
CLINICAL/FUNCTIONAL
Rudolph Virchow
1821-1902
The Father of
Modern Pathology
“All diseases are the results of visible
cell abnormalities”, i.e., abnormal
histology, i.e., histopathology’’
Diagnosis and treatment guidelines
CELL ADAPTATIONS
CELL INJURY
CELL DEATH
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
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
Understand the concept of Aging.
Adaptation
 Adaptations are reversible changes in the
size, number, phenotype, metabolic activity,
or functions of cells in response to changes in
their environment
The –plasia brothers
 HYPER HYPO- (A-)
 NORMO META DYS ANA-
HYPERPLASIA
 Hyperplasia is an increase in the number of
cells in an organ or tissue, usually resulting
in increased mass of the organ or tissue.
 physiologic or
 pathologic.
Physiologic Hyperplasia
 (1) hormonal hyperplasia
 female breast at puberty and during
pregnancy
 (1) compensatory hyperplasia
 one lobe of the liver for transplantation
Pathological hyperplasia
 Endometrial hyperplasia
 Benign prostatic hyperplasia
 viral infections, such as papillomaviruses
 hyperplasia is distinct from cancer, but
pathologic hyperplasia constitutes a fertile
soil in which cancerous proliferation may
eventually arise.
Mechanisms of Hyperplasia
 Hyperplasia is the result of growth factor–
driven proliferation of mature cells and, in
some cases, by increased output of new cells
from tissue stem cells.
 after partial hepatectomy growth factors are
produced in the liver that engage receptors
on the surviving cells and activate signaling
pathways that stimulate cell proliferation.
HYPER-PLASIA
IN-CREASE IN NUMBER OF CELLS
HYPO-PLASIA
DE-CREASE IN NUMBER OF CELLS
The –trophy brothers
 HYPER HYPO-
 DYS-
(A-)
HYPER-TROPHY
IN-CREASE IN SIZE OF CELLS
Hypertrophy
 Hypertrophy refers to an increase in the size
of cells, resulting in an increase in the size of
the organ
 Physiological and pathological
 Uterus during pregnancy
 Hypertrophy of skeletal muscles, in body
builders
 Hypertrophy of cardiac muscles
HYPO-TROPHY?
DE-CREASE IN SIZE OF CELLS?
RARELY
USED
TERM
A-TROPHY?
DE-CREASE IN SIZE OF CELLS? YES
SHRINKAGE IN CELL SIZE DUE TO
LOSS OF CELL SUBSTANCE
Atrophy examples
 Normal physiological atrophy of tissues during
intrauterine development e.g notochord and
thyroglossal duct.
 Physiological atrophy of uterus after pregnancy
Pathological atrophy
 DECREASED WORKLOAD*disuse atrophy,,,






e.g plaster of paris and muscles atrphy
DENERVATION atrophy
DECREASED BLOOD FLOW…old age and
atrophy of brain and heart
DECREASED NUTRITION.. Marasmus,
cachexia
AGING (involution)
PRESSURE
Loss of endocrine stimulation
METAPLASIA
 Metaplasia
is a reversible change in
which one differentiated cell type
(epithelial or mesenchymal) is
replaced by another cell type
 COLUMNAR SQUAMOUS (Cervix
and lung)
 SQUAMOUS COLUMNAR
(Glandular) (Stomach)
 FIBROUS BONE
Mechanism of metaplasia
 the result of a reprogramming of stem cells
that are known to exist in normal tissues, or
of undifferentiated mesenchymal cells
present in connective tissue
CELL DEATH
 APOPTOSIS vs. NECROSIS
 What is DEATH? (What is LIFE?)
DEATH is
IRREVERSIBLE
So the question is….
…NOT what is life or
death, but what is
REVERSIBLE or
IRREVERSIBLE injury
REVERSIBLE
CHANGES
REDUCED oxidative
phosphorylation
ATP depletion
Cellular “SWELLING”
IRREVERSIBLE
CHANGES
MITOCHONDRIAL
IRREVERSIBILITY
IRREVERSIBLE
MEMBRANE DEFECTS
LYSOSOMAL
DIGESTION
REVERSIBLE = INJURY
IRREVERSIBLE = DEATH
SOME INJURIES CAN LEAD
TO DEATH IF PROLONGED
and/or SEVERE enough
INJURY CAUSES (REVERSIBLE)
THE
USUAL
SUSPECTS
But…WHO
are the
THREE
WORST?
INJURY CAUSES (REVERSIBLE)
Hypoxia, (decreased O2)
PHYSICAL Agents
CHEMICAL Agents
INFECTIOUS Agents
Immunologic
Genetic
Nutritional
INJURY MECHANISMS (REVERSIBLE)
DECREASED ATP
MITOCHONDRIAL DAMAGE
INCREASED INTRACELLULAR
CALCIUM
INCREASED FREE RADICALS
INCREASED CELL MEMBRANE
PERMEABILITY
What is Death?
What is Life?
DEATH is
IRREVERSIBLE
MITOCHONDRIAL
DYSFUNCTION
PROFOUND MEMBRANE
DISTURBANCES
 LIFE is……..???
CONTINUUM
REVERSIBLE 
IRREVERSIBLE
DEATH
EM
LIGHT MICROSCOPY
GROSS APPEARANCES
DEATH:
ELECTRON MICROSCOPY
DEATH:
LIGHT MICROSCOPY
CELL DEATH
 APOPTOSIS
(“normal”
death)
 NECROSIS
(“premature”
or “untimely”
death due to
“causes”
Necrosis & Apoptosis
Morphology of cell injury
 Reversible
 Irreversible
NECROSIS BROTHERS:
 Liquefactive (Brain)
 Gangrenous (Extremities, Bowel, non-specific)
 WET
 DRY
 Fibrinoid (Rheumatoid, non-specific)
 Caseous (cheese) (Tuberculosis)
 Fat (Breast, any fat)
 Ischemic (non-specific)
 Avascular (aseptic), radiation, organ specific,
papillary
 YAHOO!
LIQUEFACTIVE NECROSIS, BRAIN
MORE LIQUID  MORE WATER
 MORE PROTONS
CASEOUS NECROSIS, TB
FIBRINOID NECROSIS
“WET” GANGRENE
“DRY” GANGRENE
Mechanism of cell injury
 Depletion of




ATP
Mitochondrial
damage
Membrane
damage by
Influx of
calcium
Free radical
injury
Damage to DNA
& Proteins
ATP depletion
Free radical injury
EXAMPLES of Cell
INJURY/NECROSIS
Ischemic (Hypoxic)
Ischemia/Reperfusion
Chemical
ISCHEMIA/REPERFUSION INJURY
NEW Damage “Theory”
CHEMICAL INJURY
“Toxic” Chemicals, e.g CCl4
Drugs, e.g tylenol
Dose Relationship
Free radicals, organelle,
DNA damage
APOPTOSIS
 a pathway of cell death that is induced by a
tightly regulated suicide program in which
cells destined to die activate enzymes
capable of degrading the cells' own nuclear
DNA and nuclear and cytoplasmic proteins
 NORMAL (preprogrammed)
 PATHOLOGIC (associated with
Necrosis)
“NORMAL” APOPTOSIS
 Embryogenesis
 Hormonal “Involution”
 Cell population control, e.g.,
“crypts”
 Post Inflammatory “Clean-up”
 Elimination of “HARMFUL” cells
 Cytotoxic T-Cells cleaning up
“PATHOLOGIC” APOPTOSIS
 DNA damage
 Accumulation of misfolded proteins
 “Toxic” effect on cells, e.g., chemicals,
pathogens
 Cell injury in certain infections.e.g. Viral
 Duct obstruction
 Tumor cells
 Apoptosis/Necrosis spectrum
Morphology of Apoptosis
 Shrinkage (pyknosis),
increased nuclear
staining
(hyperchromasia),
nuclear fragmentation
(karyorrhexis,
karryolysis), are classic
features of apoptosis
 Apoptotic bodies
Mechanism of Apoptosis
Examples of Apoptosis
 Growth Factor Deprivation
 DNA Damage
 Accumulation of Misfolded Proteins
 Apoptosis of Self-Reactive Lymphocytes
 Cytotoxic T Lymphocyte-Mediated Apoptosis
INTRAcellular
ACCUMULATIONS
 Lipids
 Neutral Fat
 Cholesterol
 “Hyaline” = any “proteinaceous” pink “glassy”
substance
 Glycogen
 Pigments (EX-ogenous, END-ogenous)
 Calcium
LIPID LAW
ALL Lipids are
YELLOW grossly
and WASHED out
(CLEAR)
microscopically
FATTY LIVER
FATTY LIVER
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
TATTOO, MICROSCOPIC
ANTHRACOSIS
Hemosiderin/Melanin/etc.
CALCIFICATION
 DYSTROPHIC (LOCAL CAUSES) (often
with FIBROSIS)
 Normal calcium and dead and dying tissues
 METASTATIC (SYSTEMIC CAUSES)
 Hypercalcemia and viable tissue
 HYPERPARATHYROIDISM
 Destruction of bone
 Vit. D disorders & Sarcoidosis
 Renal failure

“METASTATIC*” Disease
*NOT to be confused with “metastatic” calcification
CELL AGING parallels
ORGANISMAL AGING
PROGRAMMED THEORY (80%)
vs.
WEAR AND TEAR THEORY (20%)
Mechanisms of cellular aging
 DNA damage
 Decreases cellular replication
 Defective protein homeostasis