LEC2 - CELL INJURY AND CELL DEATH Flashcards
___ is one of the most crucial events in the
evolution of disease in any tissue or organ
Cell death
STRESSORS of normal cell
physiologic adaptation
pathologic adaptation
2 reason or causes of cell injury
inability to adapt and injurious stimuli
2 types of cell injury
mild and transient (reversible)
severe progression (irreversible) causing death
2 types of cell death
necrosis or apoptosis
refers to the steady state of the body processses
homeostasis
reversible functional and structural
responses to changes in physiologic states (e.g.,
pregnancy) and some pathologic stimuli, during
which new but altered steady states are achieved,
allowing the cell to survive and continue to function
Adaptations
f the limits of adaptive responses are exceeded or
if cells are exposed to injurious agents or stress, deprived of essentials nutrients, or become compromised by mutations that affect essential cellular constituents, a sequence of events follows
that is termed
cell injury
Cell injury is reversible up to a certain point, but if the stimulus persists or is severe enough from the beginning, the cell suffers irreversible injury and ultimately undergoes ___.
cell death
the end result of progressive cell
injury
cell death
, is one of the most crucial events in the
evolution of disease in any tissue or organ
cell death
cellular response to the altered physiologic stimuli, some non lethal injurious stimuli
cellular adaptations
cellular response to increased demand, increased stimulation
hyperplasia or hypertrophy
cellular response to decreased nutrients, and decreased stimulation
atrophy
cellular response to chronic irritation (physical or chemical)
metaplasia
cellular response to reduced oxygen supply, chemical injury, microbial infection
cell injury
cellular response to acute and transient
acute reversible injury, cellular swelling fatty change
cellular response to progressive ad severe including dna damage
irreversible damage leading to death
necrosis or apoptosis
cellular response to metabolic alterations, genetic, or acquired chronic injury
intracellular accumulations; calcification
cellular response to cumulative sublethal injury over long life span
cellular aging
Interferes with aerobic oxidative respiration
Hypoxia or oxygen deficiency
Common cause of cell injury and death
Hypoxia or oxygen deficiency
A loss of blood supply in a tissue due to
impeded arterial flow or reduced venous
drainage (infarction or occlusion
Hypoxia or oxygen deficiency
Most common cause of hypoxia
Ischemia
pathological causes of ischemia
Pneumonia, Anemia, carbon monoxide (CO)
poisoning
Agents commonly known as poisons (arsenic,
cyanide, or mercuric salts)
Chemical/toxic agents
how chemical or toxic agents cause cellular injury
Cause severe damage at the cellular level by
altering membrane permeability
example of Chemical/toxic agents
(arsenic, cyanide, or mercuric salts)
Toxic agents encountered in our environment
o Air pollutants
o Insecticides
o CO
o Asbestos
o Ethanol (social “stimuli”) – recreational
drug
o Therapeutic drugs
a toxic chemical that is known as the recreational drug
o Ethanol (social “stimuli”)
Infectious agents
- Viruses
- Parasite
- Bacteria
- Fungi
Immune reaction can also result in cell and tissue injury
true or false
true
Immunologic reaction examples
autoimmune
allergic reactions
immunocompromised
Genetic defects example
Congenital malformations
Sickle cell anemia
Genetic defects/deficiency of functional proteins
as cause of cell injury - Nutritional imbalances
give the etiology
o Protein-calorie insufficiency
o Vitamin deficiencies
o Nutrition causes of morbidity and mortality
Physical agents that causes cell injury
- Trauma
- Extremes of temperatures (burns and deep cold)
- Radiation, electric shock
- Sudden changes in atmospheric pressure
a non modifiable cause of cell injury wherein there’s a degenerative changes
aging
it Leads to alteration in replicative and repair abilities of individual cells and tissue
aging
a non modifiable factor that Diminished ability to respond to damage and eventually the death of cells and the organism
aging
It is useful to describe the structural alterations that occur in damaged cells
MORPHOLOGY OF CELL AND TISSUE INJURY
2 morphology that correlates with reversible cell injury
CELLULAR SWELLING
FATTY CHANGE
a morphology that correlates with reversible cell injury
is the result of failure of energy-dependent ion pumps in the plasma membrane
cellular swelling
morphology that correlates with reversible cell injury
inability to maintain ionic fluid homestasis
cellular swelling
morphology that correlates with reversible cell injury
in microscopic examination, it will appear and reveal ___
small, clear vacuoles within the cytoplasm
morphology that correlates with reversible cell injury
in cellular swelling, also known as
hydropic change or vacuolar degeneration
morphology that correlates with reversible cell injury
imbalance of the retention of fluid
cellular swelling
morphology that correlates with reversible cell injury
occurs in hypoxic injury and in various forms of toxic excesses such as chole, salt, sugar or metabolic injury
fatty change
morphology that correlates with reversible cell injury
microscopically, fatty change will appear and reveal ___
small or large lipid vacuoles in the cytoplasm
morphology that correlates with reversible cell injury
It is principally encountered in cells
participating in fat metabolism
(hepatocytes, myocardial cells)
FATTY CHANGE
intracellular changes associated with reversible injury particularly the plasma membrane
producing blebs, blunting, distortions of microvilli, and loosening, or intercellular attachments
intracellular changes associated with reversible injury particularly the mitochondrial changes
swelling and the appearance of phospholipid-rich amorphous densities
intracellular changes associated with reversible injury particularly the ribosomes
dilation of the endoplasmic reticulum detachment of ribosomes and dissociation of polysomes
intracellular changes associated with reversible injury particularly the nuclear
with clumping of chromatin (pyknosis)
intracellular changes associated with reversible injury particularly the myelin figure
phospholipid masses (cytoplasm)
derived from damaged cellular membranes
factors to consider on how cell respond to injurious stimuli
type of injury,
its duration,
and its severity (chronic or acute)
the consequences of injurious stimulus is based on
type of cells
status of cell
adaptability of cell
genetic makeup of the injured cell
Cell injury results from ___ and ___
functional and biochemical abnormalities
are the free radicals found in the environment which the body can metabolize in low numbers and lower than ATP
reactive oxygen species
what will happen if the mitochondria is damaged
damaged mitochondria –> less production of ATP –> ROS increase –> cell injury
Disturbance in calcium homeostasis
Associated with __
plasma membrane
Damaged plasma membrane will result in ___
inability to manage homeostasis due to influx of fluid (ion, sodium, calcium, potassium) leading to alteration of cells
Damaged lysosomal membrane will result in ___
leakage of cellular components and cause damage to the tissue/ cell → cell death (necrotic)
Damage to DNA and misfolding of proteins
(degraded lysosome) will result to
- Apoptosis
- Increased ROS
what are the principal targets and biochemical mechanisms of cell injury
mitochondria
calcium homeostasis
damage to cellular plasma and lysosomal membrane
damage to dna and misfolding of proteins
The major causes of ATP depletion are
reduced supply of oxygen and nutrients, mitochondrial damage,
and the actions of some toxins
Increased cytosolic Ca2+ activates a number of
enzymes, what are they
phospholipases
proteases
endonucleases
adenosine triphosphates (ATPaseS)
an enzyme that can cause membrane damage
Phospholipases
an enzyme that Break down both membrane and cytoskeletal proteins
Proteases
an enzyme that is Responsible for DNA and chromatin
fragmentation
Endonucleases
an enzyme that is very necrotic
Endonucleases
the enzyme that Hastening ATP depletion
Adenosine triphosphates (ATPaseS)
Increased intracellular Ca2+ levels may also
induce apoptosis, by ___ and by ___
direct activation of caspases
and by increasing mitochondrial permeability
describe the cell size if it’s necrosis
enlarged (swelling )
describe the cell size if it’s apoptosis
reduce /shrinkage
describe the nucleus if it’s necrosis
pyknosis–> karyorrhexis–>karyolysis
describe the nucleus if it’s apoptosis
fragmentation into nucleosome-size fragments
describe the plasma membrane if it’s necrosis
disrupted
describe the plasma membrane if it’s apoptosis
intact; altered structure; especially orientation of lipids
describe the cellular contents if it’s necrosis
enzymatic digestion, may leak out of cell
describe the cellular contents if it’s apoptosis
intact; may be released in apoptotic bodies
describe the adhacent inflamation if it;s necrosis
frequent
describe the adjacent inflammation if it’s apoptosis
no adjacent inflammation
describe the pathologic or physiologic role if it’s necrois
invariably pathologic (culmination of irreversible cell injury )
describe the physiologic or pathologic role
often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially dna damage
___is the type of cell death that is associated
with loss of membrane integrity and leakage of cellular content
Necrosis
Necrosis is associated to which causes
loss of membrane integrity
leakage of cellular contents
2 morphology of necrosis
CYTOPLASMIC CHANGES
nuclear changes
morphology of necrosis that is associated with increased eosinophilia
cytoplasmic changes
morphology of necrosis that is associated with homogenous appearance
cytoplasmic changes
morphology of necrosis that is associated with myelin figures are more prominent
cytoplasmic changes
morphology of necrosis that is associated with cytoplasm becomes vacuolated and appears “moth eaten”
cytoplasmic changes
nuclear changes is presented with 3 nuclear parts
karyolysis
pyknosis
karyorrhexis
nuclear change wherein The basophilia of the
chromatin may fade secondary
to deoxyribonuclease
(DNAse) activity
Karyolysis
nuclear change wherein it’s Characterized
by nuclear shrinkage and increased basophilia;
the DNA condenses into a solid shrunken mass
Pyknosis
Pyknotic nucleus undergoes
fragmentation. In 1 to
2 days, the nucleus
in a dead cell may
completely
disappear
Karyorrhexis
Fates of Necrotic Cells
May be digested by enzymes and disappear
Dead cells may be replaced by myelin figures
the dead cell will not disappear and digested by enzymes
if will become __, it’s the remnant that will eventually cause fibrosis and decalcify
myelin figures
Dead cells may be replaced by myelin figures,
which are either phagocytosed by other cells or further degraded into fatty acids. These fatty acids bind calcium salts, which may result in the dead cells ultimately becoming ___
calcified
Coagulative Necrosis is closely related to what organ
heart and kidney
a necrosis wherein the affected tissues exhibit a firm texture
Coagulative Necrosis
localized area of coagulative necrosis
Infarct
Nuclear changes in coagulative necrosis
Pyknosis
Karyorrhexis
Karyolysis
Contrast to coagulative necrosis
Liquefactive Necrosis
Characterized by digestion of dead cells, resulting
in transformation of the tissue (liquid viscous
mass)
Liquefactive Necrosis
It shows softening and liquefaction of tissu
Liquefactive Necrosis
It characteristically results from ischemic injury to the CNS
Liquefactive Necrosis
Liquefactive Necrosis is closely related to what organ
brain
characteristic of liquefactive necrosis
suppurative infections characterized by formation of pus (creamy yellow) common in ischemic infection in CNS - liquefaction of tissue
Seen in focal bacterial, or occasionally, fungal
infections
because microbe stimulate the
accumulation of leukocytes and liberation of
enzymes from these cells
Liquefactive Necrosis
Hypoxic death of cells within the CNS often
manifests as
liquefactive necrosis
Refers to focal areas of fat destruction, typically resulting from release of activated PANCREATIC LIPASES into the substance of the pancreas and
peritoneal cavity
Fat Necrosis
Caused by trauma to tissue with high fat content
Fat Necrosis
The fatty acids released from the digestion from calcium salts will result to
Soap formation (saponification) or dystrophic
calcification
Chalky-white area
Caseous Necrosis is closely related to what organ
lungs
Cheese-like (caseous, white) appearance to the
naked eye
Caseous Necrosis
caseous necrosis will Appears as an ____ material
on microscopic examination
amorphous eosinophilic
Structureless collection of fragmented or lysed
cells (granuloma)
Caseous Necrosis
Caseous necrosis is typical in what condition
tuberculosis
Gangrenous Necrosis is due to
vascular occlusion
Gangrenous Necrosis
complicated by bacterial
infection which leads to superimposed
liquefactive necrosis
Wet gangrene
Gangrenous Necrosis
there is only coagulative
necrosis without liquefactive necrosis
dry gangrene
Special form of necrosis, visible by light
microscopy
Fibrinoid
Usually in immune reactions in which
complexes of antigens and antibodies are
deposited in the walls of arteries
Fibrinoid
The deposited immune complexes, together with
fibrin that has leaked out of vessels
Fibrinoid
Produce a bright pink and amorphous
appearance on H&E preparations called
fibrinoid (fibrin-like) by pathologists
Fibrinoid
___is a pathway of cell death in which cells
activate enzymes that degrade the cells’ own
nuclear DNA and nuclear and cytoplasmic
proteins
Apoptosis
Apoptotic cells break up into fragments, called
___, which contain portions of the cytoplasm and nucleus
apoptotic bodies
APOPTOSIS
The process was recognized in what year
1972
Sometimes referred to as “programmed cell
death
APOPTOSIS
Apoptosis in Physiologic Situations
To eliminate cells that are no longer needed
The programmed destruction of cells during
embryogenesis
Elimination of cells that have served their
useful purpose
Elimination of potentially harmful self-reactive
lymphocytes
Cell death induced by cytotoxic T lymphocytes
Apoptosis in Pathologic Conditions
- Apoptosis eliminates cells that are genetically
altered or injured beyond repair - DNA damage
- Accumulation of misfolded proteins
- Cell injury in certain infections
- Pathologic atrophy in parenchymal organs
after duct obstruction
2 Mechanism of Apoptosis
MITOCHONDRIAL (INTRINSIC) PATHWAY
DEATH RECEPTOR (EXTRINSIC) PATHWAY
pathway of apoptosis which is responsible for apoptosis in most physiologic and pathologic situation
MITOCHONDRIAL (INTRINSIC) PATHWAY
pathway or mechanism of apoptosis wherein it’s responsible for elimination of self-reactive lymphocytes and damage by cytotoxic T lymphocytes (more toxic)
DEATH RECEPTOR (EXTRINSIC) PATHWAY
An external and internal examination of the body after death
AUTOPSY
main purpose of AUTOPSY
To ascertain the cause of death
which can be natural, homicide, suicide or
accident
Clinically what’s the purpose of autopsy
→ To confirm diagnosis
→ Discover
→ Academic interest
→ Teaching purpose
→ Research purpose
“medico-legal” what’s the purpose of autopsy
→ Identify the body
→ Ascertain cause of death
→ Discover COD
→ Determine nature and number of
injuries
→ Determine presence of poisons
→ Expectation of life for insurance purposes
→ Presence of natural disease and its
contribution to death
→ Interpretation of injuries, either criminal, suicidal or accidental
Most common manner of
death; body function failure as
a result of age, illness, or
disease
NATURAL
Unintentional manner of death
ACCIDENT
Victim intentionally takes his
or her own life; the cause of
death is usually a gunshot,
hanging, or poisoning
SUICIDE
One individual takes the life of
another intentionally or
through a negligent or
reckless act; up to the court to
determine whether the death
is a murder; in certain
circumstances, a person is
justified in killing someone
else in self-defense
HOMICIDE
The pathologist is not able to determine the manner of death, even after all internal and external examinations are completed and
toxicological tests are evaluated
UNDETERMINED
Autopsy Techniques
Virchow
Letulle
Gohn
Rokitansky
Organ remove one by one from cranial cavity
down to the abdominal organs
Virchow
For high-risk autopsies or where permission is
limited to one organ
Virchow
Good for demonstrating physical change in an
individual organ but the relationship between
various organs may be hard to interpret
Virchow
Best technique for preserving the vascular supply and relationships between organs, and for routine inspection because it is fast and the body can be made available to the undertaker
Letulle
En masse (organ) removal then subsequently dissected into organ blocks
Letulle
BY SYSTEM, Thoracic and cervical organs, abdominal organs and the urogenital system are removed in
functionally related blocks preserving anatomical
relationship
Gohn
techniques usually used in academe
Gohn and Letulle
In situ dissection combined with en bloc removal
Rokitansky
Estimation of Time of Death
algor - cool
rigor - hard
livor -
—postmortem cooling of the body
Algor Mortis
Temperature generally falls ___ every hour until the body reaches ambient temperature
1.5°F
Determine body temperature
→ At the crime scene – ____
→ At the crime lab – ___
→ At the crime scene – rectally
→ At the crime lab – in the liver
In Rigor Mortis
Normal stiffening occurs in ____ hours after death
2-3
In rigor mortis,
muscle stiffening Complete in ___ hours
6-8 hrs
rigor mortis
muscle stiffening Persist in ___ hours
12-36
Rigor Mortis
Begins with what muscle
small muscle group (head and neck)
rigor mortis or the stiffening of the muscle are Delayed in __, ____, and ____
cold, emaciation, extreme obesity
Post mortem staining, subcutaneous hypostasis,
cadaveric lividity
Livor Mortis
Livor Mortis
- Fixed in ___ hours
- Completed in ___ hours
6-8;
8-12
Determines whether body position was change
Livor Mortis
Putrefaction are hastened in
warm environment
air than water
water than buried
factors affecting Putrefaction
bacteria, moisture, temperature of
environment, medium where body lies
The type of biopsy to be performed depends on the _____, ___, ___ of the lesion
location, size and clinical impression
An ___ biopsy takes out even more
surrounding tissue
Incision Biopsy
it takes out some of the abnormality, but not all
Incision Biopsy
The doctor will slice into the lesion and remove
only a portion of it
Incision Biopsy
If the lesion is found to be cancerous, further
___ may be needed to remove or excise the entire lesion
surgery
An ____biopsy generally removes the entire area in question
excisional
Is the simplest, least invasive test and uses the
smallest needle to simply remove cells from the area of abnormality
Fine Needle Aspiration
fine needle aspiration
This is not always adequate to obtain a diagnosis,
depending on the area to be biopsied
true or false
true
Considered the primary technique for obtaining
diagnostic full-thickness skin specimens
punch biopsy
The technique involves the use of a circular blade that is rotated down through the epidermis and dermis, and into the subcutaneous fat, yielding a
3-to-4 mm cylindrical core of tissue sample
Punch Biopsy
Removes not only cells, but also a small amount of the surrounding tissue
Core Needle Biopsy
This provides additional information to assist in the examination of the lesion
core needle biopsy
____ and ____ yields pleural fluid
Thoracentesis and Chest Tube Thoracostomy
___directly aspirates pleural fluid from
lungs
Thoracentesis
aspirates pleural fluid through suction bottles
CTT / Chest Tube Thoracostomy
o A needle is inserted onto the patient’s chest
piercing the lungs
o These needle with tubes is inserted onto the
patient for several hours or days depending on the fluid content of the lungs
Chest Tube Thoracostomy
The patient is prep for bone marrow procedure
similar to CSF collection
Bone Marrow Biopsy
Bone Marrow Biopsy
Samples acquired through this procedure is either
received by ____ section or ____ section
hematology section of histopathology section
Bone Marrow Biopsy
___ are the usual end product of this
procedure
Prepared slides
Demonstrates the topographic distribution of cell types which can be obtained by ___
bone marrow
aspiration
