Cell Injury, Cell Death, and Adaptations

1. Introduction
- Pathology provides the scientific foundations for the practice of medicine -> understanding the
diseases and the basis of developing rational treatments
+ Etiology (why): origin (causes) of a disease, including underlying causes and modifying factors
+ Pathogenesis (how): the steps in development of a disease, how the initial etiological trigger
makes changes in the molecular and cellular structures, then express to the specific functional
and structural abnormalities, that specify the particular disease.
* Etiology -> Pathogenesis -> Abnormalities in cells and tissues -> Clinical manifestations
- Cells undergoes stresses/injuries -> adaptation – new states, preserve viability and function
- Adaptations exceed/harmful external stresses -> cell injury
+ cell injury is reversible -> homeostasis restores
+ stress is too severe/persistent -> irreversible injury -> cell death (crucial in developing diseases)
2. Causes of cell injury
- Hypoxia (oxygen deficiency) and ischemia (reduce blood supply) – Oxygen deprivation: necrosis
from ischemia can be more severe than from hypoxia
+ Heart diseases, lung diseases
- Toxins (potential toxic agents) – free radical agents (ROS)
+ polycyclic hydrocarbons, alcohols, drugs (acetaminophen), heavy metals
+ ROS: O2-, H2O2, -OH, acetaminophen, hemochromatosis (Fe overload)
- Infectious agents: viruses, bacteria, fungi, parasites…
- Immunologic reactions: immune reactions can result in cell and tissue injury – autoimmune,
allergic, excessive/chronic immune, cellulitis
- Genetics abnormalities: chromosomal abnormalities and mutations
- Nutritional imbalances: protein, vitamin, carb insufficiency/excessively
- Physical agents: trauma, extreme temperature, radiation, electric shock, or sudden changes on
atmosphere pressure
- Aging factors: reduce cell replication
3. Sequence of events in cell injury and cell death
a. Reversible cell injury: derangement of cellular structure and morphology that cells can
recover if the damaging stress is removed
- Injured cells:
+ cells are becoming swollen because of the failure of energy dependent ion-channel pump
in the plasma membrane -> take in water
+ accumulation of degenerated organelles and lipids
- 2 most consistent morphology of reversible injury
+ Cellular swelling: causes pallor, increases organs weight, increases turgor (pressure that
presses the cell membrane against the cell wall
(+) Hydropic change (vacuolar degeneration) – appearance of small, clear vacuoles
+ Fatty change: appearance of lipid vacuoles, mostly in organ – lipid metabolism – such as
liver
+ Other intercellular changes:
(+) alteration of plasma membrane
(+) mitochondrial changes
 (+) dilation of ER – ribosomes detachment, polysome disassociation
(+) alteration of nuclear
(+) appearance of myelin figures in the cytoplasm
- If the damaging stress is too severe, progressive -> “point of no return” -> irreversible cell
injury -> cell death
- Irreversible cell injury: no specific morphological, biochemical changes, but there are
consistent characteristics:
+ Alteration of the plasma membrane – structures, functions loss
+ Mitochondrial dysfunction – inability to restore functions
+ Structure integrity loss of DNA and chromatin
b. Cell death: when irreversible injury happens, cell death occurs – different mechanism, based
on the natural and severity
- Morphology changes occur after the loss of tissue/cell functions and viability
* Necrosis – accidental cell death: rapid, uncontrollable, morphology manifestation ->
leaking contents into blood -> inflammation
* Apoptosis – programmed cell death: relied on the gene, series of biochemical pathways,
highly controlled (intentionally cell death) -> forming of bleb -> falling off -> phagocytosis by
macrophage
c. Necrosis
- Always an indication of a pathologic process
- Cellular membrane falls apart, creating holes in the plasma membrane, leads to the leaking
of cellular contents (biomolecules, organelles, enzymes) into blood (damage-associated
molecular patterns), and triggers the process of inflammation.
- Digestion of death cells: leukocytes enzymes, and the disrupted lysosomes of the death
cells
- Micromorphology
+ Cytoplasmic changes
(+) increase eosinophilia because of the loss of RNA, and proteins denature
(+) glassy, homogenous appearance because of the glycogen loss
(+) cytoplasm becomes vacuolated when the enzymes have digested organelles
+ Nuclear changes
(+) Karyolysis: the digestion of DNA by DNase –> basophilia fades
(+) Pyknosis: the shrinking of the nucleus, and DNA gets more condense -> increase
eosinophilia
(+) Karyorrhexis: the fragmentation of pyknosis nucleus
+ Fates of necrotic cells
(+) digested by enzymes
(+) replaced by myelin figures -> phagocytosed or degraded into fatty acids (which can cause
dystrophy calcification)
- Macro morphology
+ Coagulation necrosis
(+) hypoxia/ischemia, occur in all organs, but the CNS (which will be liquefactive)
+ Liquefactive necrosis: bacteria, fungi, and cell death in CNS
+ Gangrenous necrosis: coagulation necrosis in limbs
 (+) if there is bacteria involved -> looked like liquefactive necrosis
+ Caseous necrosis: foci of tuberculous infection
(+) “cheese-like” appearance
+ Fat necrosis: focal areas of fat destruction
(+) fat is the most exposed part of the body -> fat necrosis can be due to trauma (abdominal,
breast…) or acute pancreatitis
(+) most common in breast tissue
(+) -> chalky lesions
+ Fibrinoid necrosis: special form, can only observe under light microscopy
(+) deposit of antigens and antibodies onto the blood vessels wall - hypertension
d. Apoptosis
- Can occur in healthy tissues, and not necessary associate with a pathologic cell injury
e. Autophagy
4. Mechanism of cell injury and cell death
a. Mitochondrial dysfunction and damage
b. Oxidative stress
c. Endoplasmic reticulum stress
d. Damaged membrane
e. Disturbance in calcium homeostasis
f. DNA damage
g. Clinicopathologic examples
5. Cellular adaptations to stress
a. Hypertrophy: increase the size of a tissue or cell -> increase size of an organ
b. Hyperplasia: increase in the number of tissues or cells
c. Atrophy: decrease in size of an organ, caused by the reduce in size or the decrease in
number of tissues or cells
d. Metaplasia: the change from one cell type to another cell type
6. Intracellular and extracellular depositions
a. Intracellular accumulations
b. Extracellular deposits: pathologic calcification
7. Cellular aging
Cell injury, cell death, and adaptations

1. Introduction
- Pathology – the study of structural, biochemical, and functional changes in cells, tissues, organs
that underlie disease.
+ Branches of pathology: general - systemic
+ Techniques:
- Etiology (why) – initial causes of the diseases
- Pathogenesis (how) – sequence of molecular, cellular, biochemical events lead to the disease
development
+ Incubation period: the time between the exposure to virus and the appearance of symptoms
- Morphology: the alterations in structures of tissues or cells that undergo the pathogenetic
mechanisms
+ gross: changes that can see with naked eyes – micro: microscopic structures alterations
+ Morphologic manifestations – the morphologic changes of organs affecting the normal
functions of the organs
- Homeostasis – self-regulating process, that a living cell maintains the internal balance while
adjusting to changing of external environment
- Disease occurs when homeostasis fails
+ Potentially of functional impairments, but can also be detected while asymptomatic (infected
but no symptoms)
2. Genome (pathologic basis of diseases book)
3. Causes of diseases: 8 main causes – oxygen deprivation, physical factors, chemical agents,
infectious agents, immunologic reactions, genetic abnormalities, nutrition imbalances, aging
a. Oxygen deprivation – Hypoxia: deficiency of oxygen -> depletion pf ATP, increase anaerobic
respiration in cell
- Most common cause - cell injury/death
- Cause:
+ ischemia – reduce blood flow
+ Heart, lung problems and diseases: inadequate oxygenation - cardiorespiratory failure, or
reduce the blood’s oxygen-carrying capacity - anemia, CO poisoning, severe blood loss
b. Physical factors: extreme temperature (burn, frostbite,..), radiation, electrical, mechanical
- Mostly direct factor
- Frostbite analysis
c. Chemical agents: polycyclic hydrocarbons (smokes), alcohol, drugs, toxins, free radical agents
(ROS), acetaminophen (main ingredient ion over counter painkillers)
d. Infectious agents: bacteria, virus, fungi, parasites
e. Immunologic reactions: autoimmune
f. Genetic abnormalities:
g. Nutrition imbalances: nutrition deficiency/excessive
h. Aging: reducing cells replication
4. Hypoxia – analyzing in details
5. Cellular response to stress and noxious stimuli