PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

Telomere length is maintained by?

Telomerase activity
Describe the telomerase activity in the somatic cell cycle
and in cancer cells

Certain tumor suppressor genes believed to be involved in

controlling replicative senescence
In relation to defective protein synthesis, what are the 2
pathways of protein homeostasis?

True or False. Eating more increases longevity.

2 major neurohormonal circuits that regulate metabolism
This is produced in many cell types in response to growth
hormone secretion by the pituitary gland and mimics
signaling by insulin and thereby informs the cells of the
availability of glucose promoting anabolic state, cell
growth and replication
2 downsteam targets of IGF- 1 signaling pathway
These are family of NAD- dependent protein deacetylases
At least how many sirtuins are distributed in different cellular
compartments
In addition, sirtuins are thought to promote ____
Explain why caloric restriction can increase longevity of cells
Effects of IGF- 1 can be mimicked by what drug?
Increase of sirtuins esp. with sirtuin- 6 serevs dual functions;

True or False. A constituent of wine may activates telomeres

and thus increase life- span

Nucleotide addition mediated by an enzyme called

telomerase
Present in germ cells, low level in stem cells, absent
in somatic cells
As somatic cells divide, their telomeres become
shorter until they can no longer generate new cells
to replaced damaged ones
In immortal cancer cells, telomerase is reactivated
and length is stabilized allowing cells to proliferate
indefinitely
CDKN2A locus (encodes two tumor suppressor
genes p16 or INK4a which are correlated with
chronologic age)
a. Those that maintain proteins in correctly
folded conformations (mediated by
chaperones)
b. Those that degrade misfolded proteins by
autophagy- lysosome system and ubiquitinproteasome system
FALSE
1. Insulin and IGF-1
2. Sirtuins
IGF- 1

AKT and Mtor

Sirtuins
7 types
The expression of several genes whose products
increase longevity
Restriction of calories reducing IGF increasing
the sirtuins
Rapamycin
1. Sirtuins contribute to metabolic adaptations
of caloric restriction
2. Promote genomic integrity by activating
DNA repair enzymes through deacylation
FALSE

******* NOTHING FOLLOWS********

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PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

A condition in which macrophages activate a vit. D precursor

Idiopathic hypercalcemia of infancy is termed as
Less common causes of hypercalcemia

Metastatic calcification principally affects what organs?

Describe the structure of a metastatic calcification

Massive deposition in the kidney may in time cause renal
damage called
Considered as one of the strongest independent risk factors
for many chronic dses
Cellular aging is the result of ___

Factors believed to play a role in aging

According to the DNA sequencing studies, the average

hematopoietic stem cell suffer from how many new
mutations per year?
What gene product is defective in patients with werner
syndrome?
Examples of dses that are characterized by aging at an
increased rate
A terminally non- dividing state of the cells after a fixed
number of divisions
Two mechanism that are believed to underlie cellular
senescence.
In the mechanism of replicative senescence, what happens
to the repeated sequences of telomere?
These are short repeated sequences of DNA present at the
end of the chromosomes that are important for ensuring the
complete replication of chromosomal ends and for protecting
chromosomal termini from fusion and degradation

2. Resorption of bone tissue secondary to

primary tumors of the bone or diffused
skeletal metastasis or immobilization
3. Vit. D related disorders including vit.D
intoxication, sarcoidosis, idiopathic
hypercalcemia in infant characterized by
abnormal sensitivity to vit.D
4. Renal failure retention of phosphate
secondary hyperparathyroidism
Sarcoidosis
Williams syndrome
o Aluminum intoxication
o Milk- alkali syndrome due to excessive
ingestion of calcium and antacids such as
milk or calcium carbonate
Interstitial tissues of the gastric mucosa, kidneys,
lungs, systemic arteries and pulmonary veins (all
these tissues excrete acid and therefore have an
internal alkaline compartment
Non- crystalline amorphous deposits or as
hydroxyapatite crystals
nephrocalcinosis
Age
Progressive decline in cellular function and viability
caused by genetic abnormalities and the
accumulation of cellular and molecular damage due
to the effects of exposure to exogenous influences
1. DNA damage
2. Cellular senescence
3. Defective CHON hemostasis
4. Deregulated nutrient sensing
14

DNA helicase
Bloom syndrome and ataxia- telangiectasia
Replicative senescence
Telomere attrition and activation of tumor
suppressor gene
Shortened progressively ccell cycle arrest
Telomeres

20

PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

Morphology of hemosiderin

Is systemic hemosiderosis, it is found first in what organs?

This pathologic condition is caused by abnormal deposition

of calcium salts, together with smaller amounts of Fe, Mg
and other mineral salts
Despite the normal serum levels, of calcium and in the
absence of derangements in the metabolism of calcium,
deposition of calcium salts occurs in the dying tissue, this is
termed as
What is metastatic calcification?

Dystrophic calcification

Morphology of dystrophic calcification

4 principal causes of hypercalcemia

2. Hemolytic anemias in which pre- mature

lysis of red cells release of abnormal
quantities of iron
3. Repeated blood transfusions because the
transfused red cells constitute an
exogenous load of iron
Coarse
Golden granular pigment lying within the
cells cytoplasm
Can be visualized by Prussian blue stain in
which colorless potassium ferrocyanide is
converted by iron into blue- black ferric
ferrocyanide
It is found first in the mononuclear phagocytes of the
liver, bone marrow, spleen and lymph nodes and in
scattered macrophages
Calcification

Dystrophic calcification

The deposition of calcium in normal tissues w/c is

almost always results from hypercalcemia
secondary to some disturbances in calcium
metabolism
o Encountered in areas of necrosis of any type
and in foci of enzymatic necrosis of fat
o Almost always present in atheromas of
advanced atherosclerosis
o Develops commonly in aging and damaged
heart valves
o Calcium salts appear macroscopically as fine,
white granules or clumps, often felt as gritty
deposits
o Sometimes tuberculous node is converted to
stone
o Calcium salts have basophilic amorphous
granular, sometimes clumped appearance
o They can be extra or intracellular or both
o Heterotopic bone may be formed in the focus of
calcification
o Psammoma bodies is formed after progressive
acquisition of outer layers
1. Increased secretion of PTH w/ subsequent
bone resorption and in hyperparathyroidism
due to parathyroid tumors and ectopic
secretion of PTH- related protein by
malignant tumors

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PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

Glycogen accumulation appears as _____

Glycogen accumulations occurs in patients with
These are colored substances, some of which are normal
but some are abnormal and accumulate only under special
circumstances
Two types of pigments

The most common exogenous pigment and ubiquitous air

pollutant
Accumulation of carbon or coal dust causes blackening of
the tissue of the lungs called ____
This results when aggregates of carbon dust induced a
fibroblastic reaction or even emphysema ___
Its a form of localized exogenous pigmentation where
pigments inoculated are phagocytosed by macrophages in
the dermis, where they reside forever.
A wear and tear pigment of lipids and phospholipids in
complex with CHON suggesting that it is derived through
lipid peroxidation of polyunsaturated lipids of subcellular
membranes
This pigment appears as ___
Lipofuscin accumulation is seen and prominent in ___

Examples of endogenous pigments

A non- hemoglobin derived, brown black pigment formed
when the enzyme tyrosinase catalyzes the oxidation of
tyrosine catalyzes the oxidation of tyrosine.
Rare metabolic dse characterized by accumulation of
homogentisic acid (black pigment) in the skin, connective
tissue and cartilage known as chronosis
Its a hemoglobin derived golden- yellow to brown granular
or crystalline pigment that serve as the major storage forms
of iron.
Specific transport protein of iron.
Stored form of iron
Mechanism of hemosiderin formation
After removal of iron, what will happen to the heme moiety?
What about the removed iron?

Excess hemosiderin in the body may result to deposition in

many organs and tissues, this termed as
What are the causes of hemosiderosis?

Clear vacuoles in the cytoplasm most readily stain

with Best Carmine or PAS stain (rose to violet color)
DM and glycogen storage dses
Pigments

a. Endogenous
b. Exogenous
Carbon
Anthacosis
Coal miners pneumoconiosis
Tattoos

Lipofuscin (lipochrome)

Yellow- brown, finely granular cytoplasmic, often

perinuclear pigment
Seen in cells undergoing slow, regressive changes
and is particularly prominent in the liver and heart or
aging patients with severe malnut. and cancer
cachexia.
Melanin, alkaptunuria, hemosiderin,
Melanin (the only endogenous brown- black
pigment)
Alkaptunuria

hemosiderin

Transferrin
Ferritin
Increased local or systemic iron ferritin forms
hemosiderin granules (common bruise)
Heme moiety is converted first to biliverdin (green
bile) bilirubin (red bile), while iron is incorporated
into the ferritin hemosiderin
These conversions account for the often
dramatic play of colors seen in healing
bruise
Hemosiderosis
1. Increased iron absorption due to
hemochromatosis

18

PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

Cells in atherosclerosis appears ___

In atherosclerosis, fat laden cells may rupture releasing
lipids into the extracellular spaces producing
Tumorous masses produce by clusters of foamy cells found
in subepithelial connective tissue of the skin and in tendons
The condition of focal accumulation of cholesterol- laden
macrophages in the lamina propria of the gall bladder
A lysosomal storage dse caused by mutations affecting an
enzyme involved in cholesterol trafficking resulting in
cholesterol accumulation in multiple organs
Protein accumulation appears _____

Causes of protein accumulation

This cytoskeletal protein provides flexible intracellular

scaffold that organizes the cytoplasm and resists forces
applied to the cell
Intermediate filaments are divided into 5 classes

Is an eosinophilic cytoplasmic inclusion in the liver cells that

is characteristics of alcohol liver dse.
Refer to an alteration within cells or in the EC space which
gives a homogenous glassy pink appearance on routine H &
E stains
Examples of intracellular hyaline change

Examples of extracellular hyaline change

This intracellular components seen in patients with
abnormality with either glucose or associated metabolism

Foamy (foam cells) and aggregates in the intima

produce the yellow laden atheromas
Distinctive clefts in tissue sections
Xanthomas
Cholesterolosis
Niemann- pick dse, type C

Appears as rounded, eosinophilic droplets, vacuoles

or aggregates in the cytoplasm
- They can be amorphous, fibrillar, or
crystalline in appearance
1. Reabsorption droplets in proximal renal
tubules (e.g. proteinuria)
- Appears as pink hyaline droplets within
cytoplasm of tubular cells
2. Russel bodies
- This is due to synthesis of excessive
amounts of normal secretory proteins
3. Defective intracellular transport and
secretion of critical proteins (in alpha1 antitrypsin deficiency emphysema)
4. Accumulation of cystoskeletal proteins
5. Aggregration of abnormal proteinssometimes called as proetinopathies or
protein- aggregation dses(e.g. amyloidosis)
Intermediate filaments

1. Keratin- filaments (epithelial cells)

2. Neurofilaments (neurons)
3. Desmin filaments (muscle cells)
4. Vimentin filaments (connective tissue cells)
5. Glial filaments (astrocytes)
Alcoholic hyaline (composed mainly of keratin
intermediate filaments)
Hyaline change

a. Intracellular accumulation of CHON,

b. reabsorption droplets
c. russel bodies
d. Mallory bodies
a. Collagenous fibrous tissue in old scars
b. Long- standing HTN and DM
Glycogen

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cell responses to stress and toxic insults: adaptation, injury and death
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Types of intracellular accumulations

It is described as the abnormal accumulations of

triglycerides within the parenchymal cells
Most common location of steatosis?
Causes of steatosis includes ____
In developed countries, the most common cause of steatosis
is __
What are morphological characteristics of steatosis in all
organs?
Special stains for lipids
Progressive accumulation of fatty substances in the liver
results with increased size up to __
Steatosis in liver begins with development of minute __

Mechanisms of accumulations of fatty substances

Conditions that accumulates cholesterol and cholesterol

esters resulting to fatty change.

In this condition, smooth muscle cells and macrophages

within the intimal layer of the aorta and large arteries are
filled with lipid vacuoles, most of which are cholesterol and
cholesterol esters

3. Inherited enzymes deficiencies failure to

degrade metabolite storage diseases
4. When cell has no enzymatic machinery to
degrade substance or ability to transport it
to the other sites deposition and
accumulation of abnormal exogenous
substances )e.g. silicosis or carbon
accumulation
1. Lipids- triglycerides, cholesterol, cholesterol
esters, phospholipids
2. CHON
3. Hyaline change
4. Glycogen
5. pigments
Steatosis (fatty change)
Liver, but can occur in heart, muscle and kidney
Toxins, CHON malnut., DM, obesity and anorexia
Alcohol abuse and non- alcoholic fatty liver dse.
Clear vacuoles within cytoplasm of hepatocytes,
intracellular accumulation of water and
polysaccharides that also produce clear vacuoles
Sudan IV or oil red O (orange- red color)
2- 4 times of the normal weight and transformed into
a bright yellow, soft greasy organ
Membrane- bound inclusion (liposomes) closely
applied to ER
Accumulation of fat as small vacuoles in the
cytoplasm around nucleus vacuoles coalesce
creating cleared spaces that displace the nucleus to
the periphery of the cell contiguous cell rupture
and the enclosed fat globules coalesce fatty cysts

1. Atherosclerosis
2. Xanthomas
3. Cholesterolosis
4. Niemann- pick dse, type C
Atherosclerosis

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PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

3 types of autophagy

Its an evolutionary conserved survival mechanism where, in

states of nutrients deprivation, the starved cell lives by
cannibalizing itself and recycling the digested contents
Steps of autophagy

Autophagy- related genes whose products are required for

the creation of autophagosome
It is formed when the autophagosomal membrane elongates
further and surrounds and captures its cytosolic cargo
Ubiquitin- like structure that provides coordinated action
during the elongation and closure of the autophagosomal
membrane
Autophagy is more prominent in what state of cell or type of
cell?
Autophagy plays role in human diseases such as

This specific macrophage increases the susceptibility to

tuberculosis.
A metabolic derangement that is characterize by
accumulations of substances that may be harmless or
associated with varying degree of injury.
Intracellular accumulations are located in ___
These substances are synthesized by?
4 main pathways of abnormal intracellular accumulations

1. Chaperone mediated
- Direct translocation across the lysosomal
membrane by chaperone proteins
2. Microautophagy
- Inward invagination of lysosomal membrane
for delivery
3. Macroautophagy
-major form of autophagy involving the
sequestration and transportation of portion
of cytosol in a double- membrane bound
autophagic vacuole known as
autophagosome
Autophagy

1. Formation of an isolation membrane called

phagophore (derived from the ER) and its
nucleation
2. Elongation of the vesicle
3. Maturation of the autophagosome, its fusion
with the lysosome and eventual degradation
of the contents
Atgs
Autophagosome
Microtubule- associated protein light chain

Prominent in atrophic cells which are exposed to

severe nutrient deprivation
1. Cancer
2. neurodegenerative dses like alzheimers and
Huntington dse,
3. infectious dses.
4. Inflammatory bowel dse
Macrophage- specific deletion of Atg5
Intracellular accumulations

Cytoplasm, within organelles (lysosomes) or in the

nucleus
Affected cells or produced somewhere else
1. Defect in mechanism of packaging and
transport inadequate removal of the
normal substances (e.g. fatty change or
steatosis)
2. Accumulation of abnormal substances as a
result of genetic or acquired defect in its
folding, packaging, transport, or secretion
(e.g. alpha1 anti- trypsin)

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PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
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Apoptosis induced by TNF- family of the receptors

A transmembrane pore- forming molecule which promotes

entry of the CTL granule serine proteases called granzymes
These enzymes have the ability to cleave proteins and
aspartate residues and thus activate a variety of cellular
caspases
Disorders associated with defective apoptosis and increased
cell survivial
Mutation of what gene is most common genetic abnormality
found in human cancer

Conditions associated with increased apoptosis and

excessive cell death.
This form of cell death is a hybrid that shares bot necrosis
and apoptosis

What part of the necroptosis resembles necrosis and

apoptosis?

How necroptosis starts?

What are the two unique kinases involved in necroptosis?

In necroptosis, after ligation of TNFR1 recruits RIP1 and
RIP3 into a multiprotein complex and activations results to?
True or False. Necroptosis is recognized as an important
death both in physiologic and pathologic conditions.
Another form of programmed cell death that is accompanied
by the release of fever inducing cytokine IL- 1
A multiprotein complex that function to activate caspase-1
which leaves a precursor for IL-1 and releases its
biologically active form
In pyroptosis, what are the caspases that induce death
cells?
Pyroptosis is a pathway of cell death characterized by

It is the process in which the cell eats its own contents

Autophagy involves _____

b. familial hypercholesterolemia- affected unit

is LDL receptor
c. tay- Sachs dse- affected unit is hexosamine
beta sub- unit
d. alpha1 anti- trypsin deficiency
e. creutzfeldt- Jacob dse
f. alzheimers position affected unit is A
peptide
FasL binds to fas on the same or neighboring
lymphocytes results to the elimination of the
lymphocytes that recognize self- antigens resulting
to autoimmune dses
Perforin
Granzymes

a. inappropriately low rate of apoptosis may

permit the survival of abnormal cells
TP53
a. Neurodegenerative disease
b. Ischemic injury
c. Death of virus
Necroptosis aka programmed necrosis and
caspase- independent programmed cell death
Morphologically and biochemically, it resembles
necrosis, while mechanistically, it resembles
apoptosis triggered by genetically programmed
signal transduction events
It starts in a manner similar to that of the extrinsic
pathway of apoptosis that is by ligation of a receptor
by its ligand.
Receptor associated kinase 1 and 3 (RIP 1 and RIP
3)
Caspases are not activated unlike in apoptosis
TRUE
Pyroptosis
Inflammasome

Caspase 1 and closely- related caspase 11

Swelling of cells, loss of plasma membrane integrity
and release of inflammatory mediators
Autophagy
Delivery of cytoplasmic materials to the lysosome
for degradation

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PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

What is FLIP?

Mitochondrial pathway leads to activation of the ______

caspase, while death- receptor pathway to the ____
What follows after an initiator caspase is cleaved to
generate its active form?
Two examples of executioner caspases that act on many
cellular components.

How are dead cells removed after an apoptosis?

What is present in the inner leaflet of the plasma membrane

of a healthy cells where it is recognized by several
macrophage receptor?

This are adhesive glycoproteins that are recognized by

phagocytes and macrophages.
A notable natural anti- bodies and proteins that coat the
apoptotic bodies and are recognized by the phagocytes.
How efficient the phagocytosis of apoptotic cells?

Hormone- sensitive cells deprived of relevant hormones may

die with apoptosis and follows what pathway?
These proteins accumulate in cells when DNA is damaged
and it arrest cell cycle (@ G1 phase) to allow time for repair
When DNA damage is too great to be repaired successfully,
what tendency may it cause?

How protein misfolding leads to apoptosis?

This is recognized as a feature of a number of

neurodegenerative dses caused by genetic mutations, aging
or unknown environmental factors.

Examples of dses caused by CHON misfolding

FasL inhibitory protein- binds to pro- caspase 8 but

cannot cleave and activate the caspase because it
lacks protease domain
Initiator caspase- 9; caspase-8 and 10
Enzymatic death is set in motion by rapid and
sequential activation of the executioner caspases
Caspase- 3 and 6
- one activated they cleave an inhibitor of a
cytoplasmic DNase and thus make the
DNase enzymatically active
The formation of the apoptotic bodies breaks cells
into bite- sized fragments fragments that are edible
for phagocytosis
- apoptotic cells are cleared before they
undergo a secondary necrosis
Phosphatidylserine
- in an apoptotic cell, this phospholipid flip out
and is expressed on the outer plasma
membrane
thrombospondin
C1q
So efficient that dead cells disappear often within
minutes , w/o leaving a trace and inflammation is
absent
Mitochondrial or intrinsic patheway
p53 protein
Triggers apoptosis
Normally: This activates signaling pathways that
increase the number of chaperones, enhance
proteasomal degradation of abnormal proteins and
slow protein translation reducing the load of
misfolded proteins in the cell.
Apoptotic mechanism: unregulated accumulation of
misfolded proteins activates caspases and induce
apoptosis, this is called ER stress
Intracellular accumulation of abnormally folded
proteins
deprivation of oxygen and glucose and
stress such as heat also result in protein
misfolding culminating in cell injury and
death.
a. cystic fibrosis- affected unit is cystic fibrosis
transmembrane conductance regulator
(CFTR)

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cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES
-

3 groups of the BCL family

Principal members of anti- apoptotic group
Where do apoptotic group resides and what are their fxns?

What are the 2 members of the pro- apoptosis group?

How BAX and BAK permeabilize membranes to promote
mitochondrial outer membrane permeability?

What are the members of the sensor group of intrinsic

pathway?
They act as sensors of cellular stress and damage and
regulate the balance between the other 2 groups thus acting
as ____
Describe the cascade of intrinsic pathway of apoptosis

Other mitochondrial proteins that enter the cytoplasm where

they bind to and neutralize cytoplasmic proteins that fxn as
physiologic inhibitors of apoptosis called IAPs
What is the normal fxn of IAP?
The extrinsic pathway is initiated by?

These are members of the TNFR family that contain

cytoplasmic domain involved in protein- protein interactions
that is called the death domain important for delivering
apoptotic signals
The best known death receptors
The ligand for Fas is called?
The binding site for an adapter protein that also contains a
death domain is called

increased permeability of the mitochondrial

outer membrane with consequent release of
death-inducing (pro- apoptotic) molecules
from the mitochondrial intermembrane
space into the cytoplasm
Anti- apoptotic , apoptosis and BCL2 they possess
BCL, BCL- XL, MCL1 they posses 4 BH domains
called BH14
They reside at the outer mitochondrial membrane.
They prevent leakage of cytochrome c and other
death inducing- proteins into the cytosol
BAX and BAK (they also have 4 BH domains)
Activation of BAX and BAK promote mitochondrial
outer membrane permeability by forming a channel
in the outer mitochondrial membrane allowing the
leakage of cytochrome c
BAD, BIM, BID, PUMA, NOXA, contain 1 BH
domain, third of the 4 BH domains and hence called
BH3- only domains
Arbiters of apoptosi

Cells deprived of survival signal/ DNA is damaged of

misfolded proteins activation of BH3- only
proteins and senses the damage sensors in turn
activate BAX, and BAK that forms oligomers that
insert into the mitochondrial membrane allowing the
protein from the intracellular membrane leak out into
the cytoplasm Bcl- x and Bcl- 2 are blocked and
inhibited once released into the cytoplasm,
cytochrome c binds with a protein called Apaf-1
(apoptosis activating factor 1) to form the multimeric
structure called apoptosome bind with caspase
9 setting up an auto amplification process
Smac/ DIABLO

Block the activation of caspases, including

executioners like caspases 3, and keep cells alive
Engagement of plasma membrane death receptors
on variety of cells.
Death receptors

Type 1 TNFR and related protein called Fas (CD95)

Fas ligand
FADD (fast associated death domain)

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cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

What are the morphologic changes in apoptosis?

The most characteristic feature of apoptosis?

What morphologic changes are present when cell
undergoes shrinkage in apoptosis?
Process of chromatic condensation.

Process of cytoplasmic blebs formation?

What happen to the plasma membranes during apoptosis?

True or false. Apoptosis renders inflammation.

This enzyme exists as an inactive enzyme and must
undergo cleavage to become active, that signals apoptosis
to occur.
2 processes of mechanism of apotosis

The activation of caspases depends on?

What are the 2 pathways in caspases activation.

The major mechanism of apoptosis in all mammalian cells
What is the mechanism of mitochondrial pathway?

What controls the release of mitochondrial pro- apoptotic

proteins by the BCL2 family of protein

- excess of misfolded proteins leads to a condition

called ER stress basis for several degenerative
dses of the CNS and other organs
3. cell death in certain infections- particularly by the
viral infections in which the loss of infected cells is
due to apoptosis that may be induced by the virus
T lymphocytes- an impt. host response to virus
specific for viral proteins, which induce apoptosis of
infected cells in an attempt to eliminate reservoirs of
infection significant tissue damage
4. pathologic atrophy in parenchymal organs after
duct obstruction, such occurs in the pancreas,
parotid gland and kidney
1. Cell shrinkage
2. Chromatin condensation
3. Formation of cytoplasmic blebs and
apoptotic bodies
4. Phagocytosis of apoptotic cells or cell
bodies by macrophages
Chromatin condensation
Cell size is smaller, cytoplasm is dense and
organelles are more tightly packed
Chromatin aggregates peripherally into dense
masses nucleus may break into 2 or more
fragments
Cells show extensive blebbing on the surface
fragmentation into membrane- bound apoptotic
bodies
Plasma membranes remain intact only until the last
stages when become more permeable to normally
retained solutes.
False
Caspases

1. Initiation phase- caspases become

catalytically active
2. Execution phase- caspases trigger the
degradation of critical cellular components.
Finely tuned balance between production of
apoptotic and and anti- apoptotic proteins
Mitochondrial pathway (intrinsic)
Death receptor pathway (extrinsic)
Intrinsic (mitochondrial pathway)
Results from increased permeability of the
mitochondrial outer membrane with consequent
release of death-inducing (pro- apoptotic) molecules
from the mitochondrial intermembrane space into
the cytoplasm
- Intrinsic patheay

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cell responses to stress and toxic insults: adaptation, injury and death
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Another damage that can result from reperfusion of the

ischemic tissue or cells caused by increased generation of
ROS ad nitrogen species.
Another consequence of reperfusion of the ischemic tissue
that results to depletion of ATP is _________
Other inclusions of the ischemia- reperfusion injury are ___

Two general mechanisms of toxic injury

The importance of neutrophil influx in reperfusion injury has

been demonstrated experimentally by _____-

Remains to be the major limitation to drug therapy

A pathway of cell death that is induced by a tightly regulated
intracellular program in w/c cells are destined to die
The product of fragmentation of the apoptotic cells is ____
containing portions of the cytoplasm and nucleus
In apoptotic cell, describe the plasma membrane

Explain the inflammatory reaction during apoptosis.

Apoptosis becomes pathologic when _______

Physiologic causes of apoptosis

Apoptosis in pathologic conditions;

Oxidative stress

Intracellular accumulation of calcium that opens the

MPTP
Inflammation and activation of complementary
system (IgM)
1. some chemicals can injure cells directly by
combining with critical molecular components (e.g.
mercuric chloride poisoning, cyanide poisoning and
antineoplastic chemotherapeutic agents)
2. most toxic chemicals are not biologically active in
their native form but must be converted to ROS
which then act on the target molecules
(accomplished by cytochrome P450 mixed- function
oxidase in the SER of the liver, e.g. CCl4 CCl3ROS and acetaminophen)
Lautlary effects of tx with antibodies that block
cytokines or adhesion molecules and thereby
reduce neutrophil extravasation
Chemical injury
Apoptosis
Apoptotic bodies
The plasma membrane remains intact but the
structure is altered that makes the cell tasty for
phagocytes
No leakage of cellular contents, therefore apoptotic
does not elicit inflammation in the host
Diseased cells become damaged beyond repair and
are eliminated
1. during embryogenesis e.g. implantation,
developmental involution and metamorphosis
2. involution of hormone- dependent tissue upon
hormone withdrawal e.g. endometrial breakdown
after menstruation, ovarian follicular atresia in
menopause, regression of lactating breast and
prostatic atrophy after castration
3. cell loss in proliferating cell population eg. An
immature lymphocyte
4. elimination of potentially harmful self- reactive
lymphocytes
5. death of host cells that have served their useful
purpose eg. Neutrophil in acute inflammatory
response and lymphocytes at the end of immune
response
1. DNA damage (it is better to kill the cell rather than
risk the mutations)
2. accumulation of misfolded proteins (arise bcoz of
the genetic mutations)

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cell responses to stress and toxic insults: adaptation, injury and death
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The most consistent feature of most forms of cell injury

except apoptosis is ________________.
Biochemical mechanisms that contribute to membrane
damage.

Consequences of membrane damage

Two phenomena that characterize the irreversibility of the

injury
***** PART 2 ******
This is the most common type of cell injury in the clinical
medicine primarily caused by hypoxia and obstruction.
In hypoxia, discuss the role of ischemia?

Mechanism of ischemic cell injury.

In ischemia, the death of the cell is mainly ____________

pathway
In ischemia, the dead cells may become replaced by a large
masses of phospholipid in the form of _____
Mammalian cells have developed protective responses to
hypoxic stress in which one of them is the hypoxia- inducible
factor- 1 is functions to _______
It is said that still no reliable therapeutic approach for
reducing the injurious consequences of ischemia in clinical
situations, but theres a strategy in brain and spinal ischemia
that would slow down the injury, this is _________
This injury results when the ischemic cells are reperfused
with oxygen resulting to loss of cells and exacerbate the
injury

2. oxidative modifications of proteins (formation of

protein- protein linkages)
3. lesions in DNA (chain scission, cross linking and
point lesions)
Early loss of selective membrane permeability
over membrane damage
1. ROS (by lipid peroxidation)
2. decreased phospholipid synthesis ATP
3. phospholipid breakdown accumulation of
breakdown products detergent effects on
membranes
4. cytoskeletal abnormalities (by activation of
proteases)
a. mitochondrial membrane damage opening of
MPTP ATP
b. plasma membrane damage influx of fluids
metabolites leak ATP
c. injury to lysosomal membranes
1. inability to reverse mitochondrial dysfunction
2. profound disturbances in membrane function
Ischemia
During hypoxia where anaerobic glycolysis is
utilized, ischemia compromises the delivery of the
substrates for the said process. Thats why;
ischemia tends to cause rapid and severe cell injury
than in hypoxia in an absence of ischemia.
a. oxygen oxidative phosphorylation ATP
generation failure of sodium, efflux of K+ influx
of Na and water swelling
b. loss of glycogen protein synthesis
c. cytoskeleton dispersion loss of ultrastructural
features
d. myelin figures within the cytoplasm
e. mitochondrial swelling ER dilated
Necrosis
Myelin figures
Promote new blood vessel formation, stimulates cell
survival pathways and enhance anaerobic glycolysis
Induced hypothermia (temp. 92F) in metabolic
demands of the cells, formation of the ROS,
inflammatory response
Ischemia- reperfusion injury

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cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

3 major consequences of mitochondrial damage

Component of the MPTP that is a target of the drug

cyclosporine that prevents opening of the MPTP therefore
reducing mitochondrial damage.
Describe the mechanism of injury in the increased calcium
concentration.

These are unpaired electron in an orbit, highly reactive and

can attack to modify adjacent molecules.
An important chemical mediator generated by endothelial
cells, macrophages, neurons and other cell types.
***** MEMORIZE THE TABLE ON ROS ******
How free radicals are eliminated?

Agents that block the activation and initiation of free radicals.

Enumerate enzymes that are adjacent to the site of
generation of oxidants and help decrease the production of
ROS.
Pathologic effects of free radicals

= oxygen supply glycolysis glycogen

lactic acid intracellular pH and activity of many
enzymes.
3. Influx of calcium damaging effect to cellular
components
4. structural disruption of protein synthetic apparatus
protein production
5. unfolded protein response accumulation of
unfolded proteins trigger the unfolded protein
response that may culminate cell injury and death.
6. irreversible damage to mitochondrial and
lysosomal membranes and the cell undergoes
necrosis.
1. formation of high- conductance channel in
mitochondrial membrane known as mitochondrial
permeability transition pore (MPTP) opening of
this pore loss of mitochondrial membrane
potential failure of the oxidative phos. ATP
necrosis
2. formation of ROS
3. permeability of the outer mitochondrial
membrane leakage of some caspases
activates apoptosis- inducing enzymes apoptosis
Cyclophilin D

1. intracellular calcium opening of the MPTP

ATP
2. Activation of enzymes:
a. phospholipase membrane damage
b. proteases breakdown of membrane and
cystoskeletal proteins
c. endonucleases DNA and chromatin
fragmentation
d. ATPase hastening of ATP depletion
3. induction of apoptosis by direct activation of
caspases and increasing mitochondrial permeability
Free radicals
Nitric oxide

Free radicals are inherently unstable and they are

degraded spontaneously by non- enzymatic and
enzymatic mechanisms
Anti- oxidants
1. Catalase
2. superoxide dismutase
3. glutathione peroxidase
1. lipid peroxidation in membranes (occurs when the
double bounds in unsaturated fatty acids are
attacked by oxygen- derived free radicals)

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cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

Coagulative necrosis can be seen in all blood vessels that

experience ischemia except for _____
A localized area of coagulative necrosis is termed as ____
This type of necrosis characterized by the digestion of dead
cells transforming the tissue into a liquid viscous mass
called pus
A type of necrosis thats usually applied to the limb that
develop a coagulative necrosis but exposed to bacteria and
resulted to liquefactive necrosis is called
This necrosis is derived from the friable white appearance of
the area of necrosis and most often seen in the foci of
tuberculous infection (granuloma)
This refers to the focal areas to fat destruction resulting from
the release of activated pancreatic lipases and occurs
usually in acute appendicitis.
This necrosis is seen in immune reactions involving blood
vessels where complexes of antigen and antibodies together
with the fibrin have leaked out of vessels resulting tor bright
pink and amorphous appearance.
When necrotic tissues are not promptly destroyed and
absorbed, they tend to attract calcium salts and other
minerals and become calcified known as _______
Principles that are relevant to most forms of cell injury.

Why is it that in some cases, exposure of 2 individuals to the

same toxins with the same amount would not result with the
same intensity?
Considered as the fundamental cause of necrotic cell death.
ATP depletion and reduced ATP synthesis are related to
what type of injury? And how are they produced in the body?

What are major causes of ATP depletion?

Results of 5- 10% ATP depletion.

Brain
Infarct
Liquefactive necrosis

Gangrenous necrosis

Caseous infection

Fat necrosis (chalky- white appearance)

Fibrinoid necrosis

Dystrophic calcification

a. the cellular response to injurious stimuli depends

on the type of injury, its duration and severity.
b. the consequence of cell injury depend on the
type, state and adaptability of the injured cells.
c. cell injury results from different biochemical
mechanisms acting on several essential cellular
components.
d. any injurious stimulus may simultaneously trigger
multiple interconnected mechanism that damage
cells.
This is because of the polymorphism of the genes

ATP depletion
ATP and ATP synthesis are associated with toxins
and hypoxic injuries. They are normally produced in
the body in two ways:
a. oxidative phosphorylation of ADP molecule
ATP
b. glycolytic pathways when oxygen is not present
Reduced supply of O2 and nutrients, mitochondrial
damage, and actions of toxins
1. activity of the plasma membrane energydependent sodium pump accumulation of sodium
inside the cell cellular swelling and dilation of ER
and diffusion of K from the cell
2. altered cellular energy metabolism

PATHOLOGY REVIEWER

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

Compare the characteristics of necrosis to apoptosis in

terms of cell size, nucleus, plasma membrane, cellular
contents, inflammation, pathologic/ physiologic nature.

What are the two features of reversible injury that can be

recognized under the light microscope
Cellular swelling results when _____?

When injury is of hypoxia and toxins of origin, the most likely

to manifest between swelling and fatty change is ?
First manifestation of all forms of injury to cell.
When many cells are affected by cellular swelling, it results
to ______?
Microscopic features of the cellular swelling

Ultrastructural changes of reversible cell injury

The morphologic appearance of necrosis and necroptosis is

the result of ______?
Morphology of a necrotic cell/ tissue under the microscope.

These are large, whorled, phospholipid masses derived from

damaged cell membranes that replaces the dead cells?
What events are associated with the karyolysis?

The shrinkage of the chromatin and increase of the

basophilia and the chromatin condenses into shrunken
basophilic mass?
The nuclear fragmentation of the pyknotic cell?
A type of necrosis characterized by the preservation of dead
tissues for a span of days, the tissue is firm.

These are associated to:

- ATP generation, loss of cell membrane
integrity, defects in protein synthesis,
cytoskeletal damage and DNA damage.
Necrosis: cellular swelling,
pyknosiskaryorrhexiskaryolysis, disrupted
plasma membrane, cellular contents are digested
enzyatically and leaks out of cell, frequent adjacent
inflammation and invariably pathologic.
Apoptosis: reduction in cell size, fragmentation into
nucleosome, intact but altered structure of the cell
membrane no adjacent inflammation and sometimes
physiologic, pathologic if severe and persistent.
Cellular swelling and fatty change
When the cell is incapable of maintaining ionic
homeostasis and is the result of failure of energydependent ion pumps
Fatty change (usually seen on organs dependent on
fat metabolism such as hepatocytes and myocardial
cells)
Cellular swelling
Causes pallor, increase turgor and increase in the
weight of the organ
Small clear vacuoles within the cytoplasm
representing the distended and pinched- off portion
of the ER
- Also known as hydropic change or vacuolar
degenration
a. plasma membrane alteration
b. mitochondrial changes
c. dilation of the ER, with detachment of the
polysomes and nuclear alterations
Denaturation of intracellular proteins and the
enzymatic digestion of the lethally injured cell
eosinophilia (due to loss of cytoplasmic RNA and
denatured cytoplasmic proteins), more glassy
homogenous appearance and cytoplasm becomes
vacuolated and has a moth- eaten appearance.
Myelin figures
The basophilia of the chromatic fades due to the
loss of DNA caused by enzymatic degradation of
endonucleases
Pyknosis

karyorrhexis
Coagulative necrosis

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cell responses to stress and toxic insults: adaptation, injury and death
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Hallmarks of reversible injury.

2 principal types of cell death

Describe necrosis.

How morphologic changes in necrosis develop?

Necrosis results to inflammation; this is due to what

mechanism?
Features of apoptosis

In cases when necrosis is regulated by series of signaling

pathways, but not the same with apoptosis, thus forming
also programmed death, how do you describe the process?
Enumerate the causes of cellular injury.

The deficiency in oxygen which causes cell injury by

reducing oxidative respiration.
Causes of hypoxia

Examples of physical agents that can cause cellular injury.

Chemical agents present as our daily companions that could

cause cellular injury

For a stress or noxious agents can cause damage, intrxn

should be present at _______
Histochemical and ultrastructural techniques can be used to
delineate cell death _______ minutes after cell injury?
Gross examination and light microscopy can be employed
after ______ after cell death.
Light microscopy changes of cell death in ischemia of
myocardium can be seen after _____ after injury
Describe the characteristics of a reversible injury.

oxidative phosphorylation, ATP, and cellular

swelling caused by ion concentration and water
influx.
Mitochondria and cytoskeleton are altered
Apoptosis and necrosis
The accidental and unregulated form of cell death
resulting from the damage of the d cell membrane
and loss of ion hemostasis.
Usually the pathway for injuries like trauma,
infection, toxins and ischemia
This is due to lysosomal enzymes that enter into the
cytoplasm.
Cellular contents leaking out into the exttracellulr
membrane (when the damage of the cell membrane
is severe)
Occurs when cells DNA or proteins are damaged
beyond repair.
Characterized by nuclear dissolution,
fragmentations of the cell without complete loss of
membrane integrity and theres a rapid removal of
cellular debris. Theres no leakage of cellular
contents, therefore theres no inflammation
necroptosis

O2 deprivation, physical agents, chemical agents,

infectious agents, immunologic rxns, genetic
derangements, nutritional balances
Hypoxia
Ischemia, reduced blood flow due t ocardiorespiratory failure, decreased oxygen- carrying
capacity (anemia and carbon monoxide poisoning)
and severe blood loss.
Mechanical trauma, extreme temp., radiation,
electric shock and sudden changes in atmp.
pressure.
Environmental and air pollutants, industrial and
occupational hazards, recreational drugs and
therapeutic drugs.
Molecular or biochemical level
Minutes to hours
Hours to days
4- 12 hours
Generalized swelling of the cell and organelles,
blebbing of plasma mem., detachment of ribosomes,
clumping of nuclear chromatin

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cell responses to stress and toxic insults: adaptation, injury and death
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Inadequate nutrition (marasmus, cachexia and
overproduction of TNF in cancer)
Loss of endocrine stimulation (loss of estrogen in
menupause shrinks the breast, uterus and vagina)
Pressure (tissue compression such as brain tumor
would suppress the surrounding tissue and
diminishes the blood supply)
Mnemonics: PIN WEB

What is the initial response of cell that results to atrophy?

Describe the chemical changes in an atrophic tissue.

Discuss the mechanism of atrophy.

The pathway responsible for the accelerated proteolysis

seen in variety of catabolic conditions.
Atrophy is usually accompanied by an increase process of
eating the cell itself due to deprived nutrition called _____
Describe the brown atrophy

Metaplasia is defined as?

Describe metaplasia as an adaptive response.

The most common epithelial metaplasia is ______

What happens in barrett esophagus?

A metaplasia that is characterized by the presence of

cartilage, bone or adipose tissue in areas that do not
normally have.
Mechanism of metaplasia.
What causes the differentiation of cells in metaplasia?
An example condition that exhibits link between transcription
factor dysregulation and the metaplasia.

Decrease in the cell size and organelles

decreased metabolic needs
In an atrophic tissue, cells contain fewer
mitochondria, myofilaments and RER
Atrophy results from decreased protein synthesis
and increased protein degradation. Protein
synthesis is decreased bcoz of the decreased
metabolic needs. When cells are deficient with
nutrition and are disused, it would activate the
ubiquitin ligases and target these proteins for
degradation.
Ubiquitin- proteosome pathway
autophagy
This results when some cell debris resist digestion
inside the autophagic vacuoles and remain as
residual bodies, example of this is the lipofuscin
granules and when present abundantly would give
rise to this kind of atrophy with brown appearance.
A reversible change in which one differentiated cell
is replaced by another type of cell.
When one cell type is sensitive to a particular
condition, it is being replaced by another cell type
which can withstand the environment.
Columnar- squamous metaplasia (e.g. respiratory
tract in a chronic cig. Smoker, stones in the salivary
glands, pancreas or bile ducts and in respiratory
epithelium in px with def. in vit. A
This is a squamous- columnar metaplasia under the
influence of gastric acid.
Connective tissue metaplasia

Metaplasia is caused by reprogramming of stem

cells that are known to exist or mesenchymal cells.
Signals generated by cytokines, growth factors and
ECM components.
Retinoic acid deficiency. (Vit. A)

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cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

Other mechanisms that also result to hypertrophy

What happens to the heart muscle in the event that the

cardiac muscle can no longer cope up with the increased
burden?
What is hyperplasia?

Describe the two types of physiologic hyperplasia.

Pathologic hyperplasia is mostly caused by ___?

Hyperplasia in comparison to cancer.

Other diseases that hyperplasia is a characteristic

Describe the mechanism of hyperplasia.

Define atrophy.

Physiologic atrophy

Causes of pathologic atrophy

is exercise- induced and significant in physiologic

hypertrophy and the signaling downstream of gprotein couped receptors which is induced by
growth factors and are important in pathologic
hypertrophy these pathways activate a set of
transcription factors such as GATA4, NFAT and
MEF2 working to increase production of proteins
HYPERTROPHY
a. switch of contractile proteins from adult to infant
or neonatal forms (e.g. alpha- isoform of myosin
heavy chain is replaced by beta- isoform
b. re- expression of some genes that only expressed
during development (e.g. in cardiac hypertrophy,
ANF is only expressed before birth and it is reinduced when there is hypertrophy)
The cardiac muscle is regress and the most
important are the lysis and loss of myofibrillar
contractile element death of myocyte cardiac
failure (net effect)
Refers to the increase of number of cells in an organ
in response to stimulus (only for dividing cell)
It can be physiologic and pathologic
Hormonal hyperplasia- a need to the hormonal
activity of hormone- sensitive organs (breast during
puberty)
Compensatory hyperplasia- increased of tissue after
a damage or resection (liver after partial
hepatectomy)
Excessive or inappropriate actions of hormones or
growth factors acting on the target cells (e.g.
endometrial hyperplasia, BPHP
- These are usually controlled and regress
when the hormones stimulation is
eliminated
Cancer and hyperplasia are distinct from each other
but the hyperplasia serves as a good soil for a
cancer arise.
Viral infection (eg papillomavirus)
Hyperplasia is a result of growth- factor driven
proliferation of mature cells, and some cases, by
increased output of new cells from tissue stem cells.
e.g. is the liver tissue regeneration
This refers to the decrease in size of the tissue
resulting from a decrease in cell size and number.
This common in normal development (notochord
and the thyroglossal duct) and the shrinkage of the
uterus after parturition.
Decreased workload (atrophy of disuse)
Loss of innervation (denervation atrophy)
Diminished blood supply (e.g. brain atrophy, senile
atrophy)

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cell responses to stress and toxic insults: adaptation, injury and death
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What response is expected from the cell if the nature of

stimulus is irreversible injury?
What response is expected from the cell if the nature of
stimulus is metabolic alterations; genetic or acquired, or
chronic injury?
What response is expected from the cell if the nature of
stimulus is cumulative sublethal inury over life span?
How does cell injury is initiated?

What are the stages of progressive impairment following

different type of insults?
The cellular injury becomes irreversible when?
Describe briefly the 2 principal pathways of cell death.

This cellular response is associated with the metabolic

derangements and sublethal chronic injury.
What are the common substances accumulated inside the
cell following an injury or stress?
The result of progressive decline in cellular fxn and viability
caused by genetic abnormalities and the accumulaton of
cellular and molecular damage due to the effects of
exposure to exogenous influences is ____?
These are reversible changes in size, number phenotype
and metabolic activity or fxns of cells in response to the
changes
In hypertrophy, the increase of the number of cells is due to?

TRUE of FALSE. Hypertrophied organ has new cells?

What type of cell would respond to hypertrophy only?

This type of hypertrophy is caused by the increased fxnal

demand or stimulation by hormones and growth factors
What is the most common stimulus of muscle hypertrophy?
The massive enlargement of the uterus during pregnant is
an example of physiologic hypertrophy caused by ___?
In pathologic hypertrophy, the enlargement (esp. the
muscle) is due to the ______?
Discuss the 3 steps in molecular pathogenesis of cardiac
hypertrophy.

Cell death; necrosis or apoptosis

Intracellular accumulations; calcifications

Cellular aging
This follows when the adaptive response is
exceeded, of if the cell is exposed to injurious
agents or stress, deprived of essential nutrients or
compromised by mutation that affects the cellular
constituents.
Adaptation reversible injury cell death
The stimulus persists or severe enough from the
beginning cell death
Necrosis- a pathologic and non- programmed cell
death
Apoptosis- a physiologic process, programmed cell
death
Autophagy- this also leads to cell death when the
cell is deprived of the an essential nutrient
Cellular accumulations
CHON, CHO, lipids and Ca (leads to calcification)
Cellular aging

Adaptations

Synthesis and assembly of additional intracellular

structural components of the cells
False. Just larger cells
Non- dividing cell (e.g. myocardial fibers), while
dividing cells can undedrgo hyperplasia
hypertrophy
Physiologic hypertrophy (eg. Muscle of the heart)
Increase workload
hormones
synthesis of proteins and number of myofilaments
by the muscle, strength and work capacity as a
whole
Integrated actions of mechanical sensors such as
TGF- beta1, IGF-1 and FGF (these triggers the
increased workload) these signals will activate
transduction pathways (a. PI3K/Akt pathway which

cell responses to stress and toxic insults: adaptation, injury and death
Dr. MONTES

PATHOLOGY REVIEWER

.
QUESTIONS

The study of the structural, biochemical, and functional

changes in cells, tissues and organs that underlie the
disease.
This field of study deals with the examining the underlying
mechanisms on organ specific diseases such as ischemic
heart disease.
4 aspects of disease

2 groups of etiology of disease?

This refers to the sequence of cellular, biochemical or

molecular events that follow the exposure of cells.
Describe the morphologic changes of the disease.
What type of therapy is being used for tx of cancer?
This reveals the genetic differences that predict the behavior
of the tumor and response to therapy
The end results of genetic, chemical and structural changes
in cells and tissues.
It is believed that all forms of disease start with?
What determines the range of fxn and structure of the
normal cell?

What do you call the steady state of the cell?

This refers to the revesible fxntional and structural
responses to more severe physiologic states and some
pathologic stimuli, during which new but altered steady state
of the cell is achieved and allow cell to survive and continue
to fxn?
Enumerate the adaptive response of the cell to injury or
trauma.

What response is expected from the cell if the nature of

stimulus is an altered physiologic stimuli or nonlethal injury?
What response is expected from the cell if the nature of
stimulus is decreased nutrients/ stimulation?
What response is expected from the cell if the nature of
stimulus is chronic irritation?
What response is expected from the cell if the nature of
stimulus is increased demand and stimulation?
What response is expected from the cell if the nature of
stimulus is reduced of oxygen supply, chemical injury or
microbial infection?

ANSWERS

pathology

Systemic pathology

a. etiology or cause
b. pathogenesis
c. morphologic changes
d. clinical manifestations
a. genetic- inherited mutations and dse- associated
gene variants, polymorphism
b. acquired- nutrition, chemical, chemical or physical
Pathogenesis
Refers to the structural alteration of cells or tissues
either characteristic of dse or diagnostic of the agent
Molecular targeted therapy
Morphologic changes (molecular analysis)
Functional derangements and clinical manifestations
Molecular or structural alteration in cells.
1. state of metabolism, differentiation, and
specialization
2. constraints of the neighboring cells
3. availability of the metabolic substrates
Homeostasis
adaptation

a. hypertrophy- increase in the size of cells and

fxnal activity
b. hyperplasia- increase in the number of cells
c. atrophy- decrease in the size of cell and fxnal
activity
d. metaplasia- change in the phenotype of cells
Cellular adaptation
Atrophy
Metaplasia
Hyperplasia, hypertrophy
Cell injury