Basic
Pathology
Cell Injury
Death
Adaptations
Etiology:Origin => Causes, Modifying Factors (Why (
in developmentof disease (How)
steps
Pathogenesis:
Morphology:Changes in gross
or
Microscopic Appearance
Cellular Response to stress & Noxious Stimuli
Cellular Adaptations
Hypertrophy
Increase in cell size
-
Prominentin
of Mitosis
Ex.
Leither phisiologic or
organs
with cell
incapable
pathologic
Pregnancy Uterns enlargement(also Hyperplasia
2. Avid
Weightlifter - Hypertrophy ofSkeletal Muscles
3.
(Pathologic Hypertension, Aortic valve disease Cardiac Enlargement.
7.
=>
-
Hyperplasia
-
EX,
Increase in cell number
1. (Hormonal) Proliferation of Breast(Glandular
and
2.
pregnancy
Epithelium)
during puberty
(Compensatory) Rejected Liver=>Restoring of cells (Inception
=
12hr)
Tree
easiertel,tegenForetplign in
Atrophy wrinkagein
Causes:
1.
Decreased Workload
of Innervation
2.
Loss
3.
Diminished blood supply
Nutrition)
Pathway
*
Atrophy is often accompanied
by Autophagy
Inadequate
4.
Loss of Endocrine
5.
Stimulation
Aging (Senile Atrophy)
Metaplasia
-One
is
-
change
A
reversible
-
adultcell
replaced by
type (Epithelial
or
Mesenchymal)
another adultcell
type
To better withstand the adverse
environment
EX.
to
7. The
Squamous
May be able
the noxious
Change:Habitual Smokers
Xchemicals cigarette
survive
in
(Epithelial cells of Trachea & Bronchi) Normal ciliated Columnar->Stratified Squamous
=>
Importantprotective
=>
2.
If
Metaplasmic
mechanisms
Change
are
lost (Mucus Secretion,
Persistent May Predispose to
->
Ciliary
Clearance)
MalignantTransformation
S
Cell Death
Appstosis
(Features)
E
Necrosis
imatin
(Shrinkage) Cell Size Enlarged (Swelling)
into
Nucleus Pykny,"Karyorhexis
Fragmentation
Karyolisis
nucleosome
Reduced
size
e
fragments
Plasma
Membrane
Intact
Disrupted
E
Cellular
Digestion
contents Enzymatic
in apoptotic
Mayleak outof cell
bodies
Intact, may
released
be
jacent
Frequentes
Causes of Cell
Genetic Factors
Oxygen Deprivation &
①
Hypoxia
-
or
O2
② Chemical
poisoning
Agents
Excess ofinnocuous substances
Glucose, salt, water etc.)
Poisons, Toxic
-
Agents
Virus, Bacteria,Fungi, Protozoans
Immunologic
④
Accumulation of Misfolded
Allergic Reaction
Proteins
⑥IUntritional Imbalances
-
Protein calorie
-
Specific
insufficiency
Vitamin
deficiencies
Physical Agents
&
Trauma, Extreme
-
temperature
radiation, electric shock
Reaction 8 Aging
-Autoimmune Reaction
-
-
-
3
OInfections
Agents
-
Functional Proteins
-Deficiency of
deficiency
Pneumonia, Blood loss anemia, CO
-
-
Injury
-
Alterations
in
repair abilities
Diminished
=>
damag
replicative
and
abilityto respond to
The Morphology of Cell & Tissue
Injury
consistently
2 Phenomena
characterize irreversibility:
-
Inability to correct
Mitochondrial
-
Reversible
o Cellular
nability
Swelling
-
hypertrophy
form vacuoles spinched
off
ER
may show
Tissues&
Profound disturbances in
membrane function
Injury
Fatty Change
②
tomaintain ionic and
homeostasis
-
dysfunction
and
segments)
Organs may perform pallor
As a resultof
Capillaries)
Compression of
-
Lipid vacuoles in cytoplasm
in Hepatocytes & Myocardial
Primarily
metabolism)
-
·Fat
* Intracellular
Changes
a) Plasma Alterations
b) Mitochondrial
Changes
c) Dilation of ER
d) Nuclear Alterations
Ilumping of Chromatin)
Necrosis (Irreversible Injury)
-
Loss of Membrane
culminating
Leakage of cellular contents
Integrity
in dissolution of cells.
+
①Cytoplasmic Changes
-
-
-
in
Imparted by RNA
Cytoplasm
Increased Eosinophilia & Decreased Basophilia (HOE
Stains)
2.
Binding ofeosin to denatured cytoplasmic proteins
Loss of
Glycogen Particles -> Glassy, Homogeneous
Appearance
Myelin figures and distruptions of Membrane and Organelles are prominent
② Nuclear
-
~
Changes
(Breakdown of DNA
Pyknosis:Nuclear Shrinkage & Increased Basophilia
(Nucleus Condensation)
-
-
Karyorhexis:Pyknotic nucleus undergoes fragmentation
Karyolysis:The basophilia of chromatin may fade
Presumably secondary to Deoxyribonuclease (DNase) activity
=>
& Chromatin)
Morphologic
①
-
Coagulative Necrosis ( )
Tissue architecture is
-
preserved for several
Denatures not
days
I
only structural proteins butalso Enzymes (Lysosomal)
Blocking
=>
-
Patterns of Tissue Necrosis
the
Proteolysis
of the dead cells
Characteristic of
Infarcts (Ischemic Necrosis)
lexceptBrain)
or
hypoxic cell death
e) very little structural framwork in neural tissue
In CNS ischemia causes
=>
Liquefactive
Necrosis
e Inductions
focused Ultrasound]
Treatments [Radiofrequency RE)
energy, High-intensity
Preservation in Surgeries (Help stop
Used for Organ
Ex. Liver Resection
-
-
Margin
Used for cancers
Bleeding)
② Liquefactive Necrosis (HSE)
-
-
-
Focal bacterial, fungal Infections
Microbesstimulatetheaccumulationoifnflammatory
Hypoxia in CNS often
evokes
cells and
enteres
Liquefactive Necrosis
~> Loss
of blood supply
Gangrene=Coagulative Liquefaction
* Wet
May occur in Diabetes
=>
+
Malitis
DiabetesMalitis
Tissues expose to excessive
sugar
Insulin to obtain Glucose (
(Endothelial cells, Brain Cells, Erythrocytes don't
require
2. Vascular
cause problems on absorption of Nutrition &
damages
Oxygen
Tissues startdying
* Maggot Therapy (****) => Clear dead tissues, disinfect, stimulate
(Maggots release enzymes & antibiotics
-
=>
Healing
③ Caseous Necrosis
(cheese like)
**t
Mostoften encountered in tuberculous Infection
-
-
Unlike
Coagulative Necrosis, the tissue architecture is completely
obliterated and
cellular outlines can'tbe dicerned
Often enclosed within
border
-
a
distinctive
inflammatory
④
Fat Necrosis
Typically resulting from release of
-
pancreatic lipases into the substance of
and the
-
-
peritoneal cavity
pancreas
known as "Acute Pancreatitis"(IAEA)
acids released from enzymatic reactions
↳ Combine with Calcium (Ca) =>
white areas
visible
chalky
grossly
CFat
Saponification)
⑤
Fibrinoid Necrosis t
Fibrinoid Deposited immune complexFibrin (leaked outof vessels)
=
-
&From
-
AFAR IFE
Complexes
are
Fibrinogen
of antigens & antibodies
deposited in the walls
of arteries
Mechanisms of Cell
① Depletion of ATP
-
ATP-dependention pumps (activity +)
E
Nat, Ca2YH2O influx, Kt eflux
dilated ER
swelling,
Cat brings
damaging effects
Anaerobic Glycolysis'
↳
Lactic Acid
Cell
-
Glycogent
↳ pHG cellular
-
Structural
Enzymes' Activity +
distruption ofthe protein
synthetic apparatus
Injury
②Mitochondrial
-
-
-
Damage and dysfunction
Failure of Oxidative Phosphorylation -> Depletion of ATP
Formation of Reactive
Formation of
Mitochondrial
-> pH changes
(ROS) -> Deleterious
Species
Oxygen
High-Conductance channels
on
Mitochondrial Membrane
Permeability Transition Pore) -> Loss of Membrane
-> Further
compromising oxidative
Effects
phosphorylation
Potential
③ Calcium Influx
*
-
cytosolicCatusually lower than extracellular
Cat'activates a number
of
a) Phospholipases (Membrane
or
sequestered Mitochondrial
enzymes:
Damage)
b) Proteases (Breakdown of Membrane and Cytoskeletal Proteins)
c) Endonucleases (DNA& Chromatin
d) Adenosine
-
Triphosphatases (ATPases) (Hastening ATP Depletion)
Induction of Apoptosis
By directactivation caspases
=>
&
of
Increasing
Fragmentation)
Mitochondrial
Permeability
④
Accumulation ofOxygen-Derived Free radicals
Reactive
-
ROS
-
is
* Oxidative Stress
Oxygen Species (ROS)
produced in small amounts during Mitochondrial Respiration & Energy Generation (All Cells)
ROS produced in
phagocytic leukocytes
as a
* Free Radicals increased under several circumstances
The
-
-
-
bsorption RadiantEnergy (WV Light, X-rays), ROS
a
of
Inflammation Produced by
Leukocytes
The
metabolism exogenous chemicals
*
ingested Microbes & other substances
weapon to digest
->
enzymatic
Pathologic
of
Effects
Intracellular
concentration
Regulated.
is
tightly
⑤
Defects
A) Decreased Phospholipid
in
Membrane
Permeability
Synthesis:ATracer
including Mitochondria
membranes
effects
Cytosolic Cat*->Activation of
B) Increased Phospholipid Breakdown:
Phospholipases
CROS:Lipid Peroxidation
D) Cytoskeletal Abnormalities:
E) Lipid Breakdown Products
Unesterified free
acids,
fatty
·
·
acyl
carnitine, lysophospholipids
Catabolic Products
->
May also insertinto Lipid bilayer exchange with membrane phospholipids
or
Changes in permeability & Electrophysiologic alterations
=>
Damage to DNA & Proteins
Damaged DNA
-
->
-
Unrepairable
Accumulation of
Misfolded Proteins
:.
Apoptosis
Ischemic and
Ischemia
-
-
-
Hypoxic Injury
Reperfusion Injury
The restoration of blood flow to ischemic but viable
tissues results, paradoxically, in the death of cells
that are not otherwise irreversibly injured.
ROS
Reoxygenation by
Mitochondrial
Action of oxidation
ROSA(From
Parenchymal,
incomplete
endothelial and infiltrating
Leukocytes)
Damage -> Incomplete reduction of O2
Cellular antioxidantdefense mechanisms
-
is
may
be
compromised
by Ischemia
Inflammation
Increased influx of
Leukocytes & Plasma Proteins
Activation of
Complement
System By products exacerbate cellInjury & Inflammation
->