Ch1-Cell - BMC Dentists 2011
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Transcript Ch1-Cell - BMC Dentists 2011
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