First Shift PATHOLOGY First Cluster Exam

Pathology Lecture 1:
Cellular Adaptation, Injury, and Necrosis

Histologic Principles
1. Homeostatic state is dependent on the
environment
2. Change causes stress on the cell
3. Type of response depends on the quality of the
stimulus (severity, duration), and of the cell
(health, type, etc.) by the time the stimulus is
applied
Availability of nutrients

The Cell Cycle

- Usually normal cells are in the resting phase for
the longest time
Continuously dividing cells undergo continuous
cell cycles but the resting phase (G1) is still the
longest phase
After G1, S phase > doubling of DNA content
in the nucleus (nucleus is bigger and
hyperchromatic) Mechanisms of Adaptation
G2: cell taking a break after S phase 1. Increasing cellular activity
Mitotic phase: results in 2 daughter cells that will Size (hypertrophy)
then undergo a long G1 phase again Number (hyperplasia)
- Terminally differentiated cells are in the G0 phase 2. Decreasing cellular activity
Can go into S phase ONLY when provoked/ Atrophy
stimulated 3. Altering cellular structure
- Labile cells Metaplasia
Continuously cycling cells
Ex. epithelial cells, RBC Patterns of Cellular Adaptation
- Undifferentiated stem cell layer only of the - A reversible type of cellular response
epithelia - Either hypertrophy or hyperplasia, or both
- Stable cells hypertrophy and hyperplasia as a response to
Facultative dividers environmental stresses
Ex. collagenous fibers deposited by fibroblasts - Removal of the stressful stimulus can reverse the
- Fibroblast cell cycle stimulated by wound cellular response
formation - The number of cells in an area is dictated by the
Ex. smooth muscles number of mitoses and the number of cell deaths
Ex. hepatocytes
Ex. bone and cartilage
- Permanent cells
Terminally differentiated cells
Cannot divide; can only hypertrophy
Ex. cardiac muscle
Ex. skeletal muscles
Ex. neurons
Ex. terminally differentiated epithelial cells

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First Shift PATHOLOGY
Pure Hypertrophy
- Increase in the size of an organ due to increase in
size of component cells
- Pure hypertrophy (without hyperplasia) in cardiac
and skeletal muscle cells ONLY
Neurons do not undergo this even in response
to environmental stimuli
Overthinking will not lead to brain hypertrophy
- It is a response to:
Increased functional demand
Increased genetic material in the cell (because
S and G2 phases can be undergone)
- But cells cannot enter the mitotic phase
- Cells are arrested in the S phase form (big
and hyperchromatic nucleus because of the
doubling of chromatin material) > squaring
of the nucleus and wider diameter of the cells
- Increased cellular size due to increased
functional demand leading to multiplication of
important organelles such as the
mitochondria and ER, as well as other
specialized organelles such as the actin and
myosin microfilaments in enlarged striated
muscle
- Ex. concentric hypertrophy of the left ventricle
Increased thickness of the left ventricular wall
Smaller lumen of the left ventricle
Very small cardiac output
Combined Hypertrophy and Hyperplasia
- Due also to increased functional demand
- Hypertrophy a prelude to hyperplasia (hypertrophy
then mitosis)
Hyperplasia
- Increase in size of tissue due to increased number
of component cells
- Due to hormonal stimulation
Ex. breasts in puberty due to estrogen (from
granulosa cells)
- Nuns, single women unopposed estrogen
- Exogenous hormones
- Tumors
Ex. hyperthyroid goiter due to TSH
- Increased TSH/mimic molecule to the TSH
(irregular borders of the follicles > stretched
out basement membrane)
Scalloping of the colloid near the follicular
cells
Ex. prostate enlargement due to testosterone
- Increase of fibromuscular stromal cells
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First Cluster Exam
- Semi-immortal characteristic number of
cell deaths in this epithelium is normal, inc in
number, dec in mortality rate (intracellular
invaginations in the glands)
Ex. endometrium in the proliferative phase
- Due to more cells lining the glandular
structures
- Straight glands > round tubular glands
Abnormal uterine teating
If under the microscope it is more cellular
> hyperplasia
Stroma is highly cellular
- Also can lead to luminal invaginations of the
epithelial lining > increased number of
epithelial cells stepping on the basement
membrane
Ex. pregnant vs non-pregnant uterus
- After ovulation, corpus luteum appears in the
uterus
- In pregnancy, corpus luteum of pregnancy
appears lasts longer
Placenta: trophoblastic cells > HCG
NOT permanent > removal of placenta
and HCG > reverts back to normal size
- Due to increased functional demand
Ex. hyperplasia in bone marrow due to chronic
blood loss
- Secondary polycythemia
Ex. lymph node hyperplasia due to inflammation
- Increased B cells > increased size of
germinal centers > increasing number of
the components in response to infection
- Lymph nodes become palpable
- Due to persistent cellular injury
Decreased Functional Demand
- Disuse of tissue
- Inadequate nutrients
- Lack of hormonal stimulation
- Denervation
- Poor perfusion
- Aging
> leads to a decrease in cell size (atrophy) or a
decrease in cell number (involution), or a
combination
> regrowth can happen when the abnormal
environment is removed; changes are reversible
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Atrophy
- Diminution in size or function of an organ due to a
diminution in the size of its component cells
- Fibrosis is present where there are previous
atrophic cells further reduces the size of the
organ
- Ex. cryptochordism results in testicular atrophy due
to the temperature of the pelvic cavity
Inc temperature > testes does not descend
- Small seminiferous tubules without gametes
- Only nuclei of the sertoli cells
- More stroma (fibrosis)
- More Leydig cells (hyperplasia)
Accompanied with testicular atrophy
- Ex. rhabdomyocytes in the skeletal muscle
Rhabdomyolysis (skeletal muscle atrophy) >
shrunken cells
Due to denervation could cause atrophy
- Disease of the anterior horn neurons >
could go to the myoneural junction which
stimulates the muscle
- Seen in poliomyelitis or spinal cord injury
Due to disuse of the muscle
- Seen in arthritis
Due to protein-energy malnutrition
- Kwasiorkor, Marasmus
Due to aging
- Widened gyri and sulci in a person with
Alzheimers disease
Presence of neurofibrillary tangles usually
in the frontal and parietal lobes
- Thinned out endometrium
Stroma is fibrous
No more hormonal stimulation from
estrogen
Seen in hyperplasia of nuns and single
women
Tumor of granulosa cells in the ovary
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First Cluster Exam
Metaplasia
- Conversion to one differentiated, mature cell type
to another
Ex. columnar bronchial epithelium
(pseudostratified columnar epithelium with cilia
and goblet cells) converted into squamous
epithelium in smokers > squamous
metaplasia
Ex. chronic infection in cervix can lead to
squamous metaplasia of endocervical glandular
epithelium
- Normally tall columnar cells with basal
oriented nuclei stratified squamous
epithelium
Ex. gastric metaplasia
Ex. intestinal metaplasia or Barretts esophagus
- Metaplasia of the distal esophagus becomes
tall columnar cells with goblet cells (intestinal)
to produce mucin to counter the influx of
gastric acid in GERD
Ex. basal cell or reserve cell or stem cell
hyperplasia (in the basement membrane)
- Can elect not to become their usual fate due
to environmental stress
- Could either differentiate into squamous cells
(squamous metaplasia; stimulated by chronic
inflammation in the surface > cardinal signs
of inflammation including edema, leading to
friction of the epithelial lining > need of the
cell to adapt to something that could resist
friction which is stratified squamous
epithelium)
- Loss of organization, differentiation and
maturation of cells
Control Mechanisms of Adaptation
- Limit adaptations
Growth factors
- Suppressor factors
Contact inhibition factors
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First Shift PATHOLOGY First Cluster Exam

Cellular Responses to Injury Cell Death

Causes of Cell Injury
- Hypoxia
- Genetic derangements
- Nutritional imbalances
- Physical and chemical factors

Sublethal Injury
- Swelling of mitochondria, ER can lead to
cellular swelling
Fuses with lysosomes through
autophagocytosis > residual body
lipofuscin pigment appears
- Loss of ribosomes
- Stable nucleus*
- Cytoskeleten converge in some parts and
make ipon-ipon
Tapos naiwan yung ibang part kasi
nakahanap ng bago becomes bleb, leaving
some parts of the cell vulnerable kasi
iniwan nga
- Removing the stimulus at the proper time
will reverse changes

Lethal Injury
- All other organelles will swell and fall off
All mitochondria and ER will swell
All ribosomes will fall from the ER
Membranes of lysosomes will be
stretched out > acid hydrolases will
eat up other organelles
- Nucleus could have heterochromatin
(inertly active)
Clumping will occur > becomes a
crumpled, small, hyperchromatic
nucleus (pyknotic)
Can break down into smaller fragments
(karyorrhexis)
Karyolysis > breakdown into very
small fragments
- Cell membranes will continue to
aggregate in one area
Causes larger blebs
Loss of gate control in the cell membrane, more
vulnerable > anything can enter or exit the cell

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First Shift PATHOLOGY First Cluster Exam

Necrosis
- There is always a pathologic stimuli in the
environment
Hypoxia, toxins
- Cellular swelling, coagulation necrosis, destruction
of organelles
- Random diffuse ATP depletion, membrane injury,
free radical damage
- Random DNA breakdown mechanism
- Inflammation as the tissue reaction

Apoptosis
- Can be due to a physiologic or pathologic
stimuli
- Programmed cell death
- Affects single cells, chromatin condensation,
fomration of apoptotic bodies
- DNA breakdown mechanism: internucleosomal
gene activation leading to synthesis of
endonucleases
- Loss of cellular modifications such as villi
- No inflammation, phagocytosis

Apoptosis
- Execution Phase
Shrinkage
Chromatin condensation
Organelles still intact
Chromosome cleavage into nucleosome
fragments
- Degradation Phase
Fragmentation of the apoptotic cells bodies
Body contains nucleosomal fragments and
viable organelles
- Phagocytosis/Degradation
Either by phagosomes or macrophages
Fragments of apoptosed cells are engulfed by
surrounding cells (wandering macrophages)
All organelles left, except the nucleus, are left
VIABLE and INTACT > can be used again

Necrosis v.s Autolysis

- Spectrum of morphologic changes that follow cell
death in living tissue
Patient is ALIVE in necrosis with a pathologic
stimulus, with chance for repair
Patient is DEAD in autolysis (iniwan yung baboy
para mabulok sa kotse)

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First Shift PATHOLOGY First Cluster Exam

Morphologic Patterns of Necrosis Liquefactive Necrosis

Coagulative Necrosis - Ex. hypoxia* in the brain, or infection by a pyogenic
- Ex. in myocardial infarction organism
- Stimulus: hypoxia, ischemia, anoxia - Total loss of the cell
Pag sa heart yung ischemia, infarction No ghost outlines
- Nucleus disintegrates (karyolysis) > ghost cell Instead, leave behind necrotic debris
shape outlines remain
- Inflammatory reaction could also occur
- All organs in the body can undergo coagulation
necrosis EXCEPT for the brain (liquefactive
necrosis)

- Intense inflammatory reaction with lots of

neutrophils infiltrating
- Disintegrated blood vessels leading to free-floating
RBCs in the area
- Seen elsewhere in the body when caused by
INFECTION > pus infection
Ex. staphylococcus aureus, beta-hemolytic
streptococci
- If liquefactive necrosis is bound by a fibrous
capsule, it is called an abscess
Ex. liver abscess

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First Shift PATHOLOGY First Cluster Exam

Caseous Necrosis
- Seen within a granuloma, or in the
center of the granuloma (rimmed by
lymphocytes, activated macrophages,
histiocytes in the lungs)
- Ex. cavitary lung lesions in
tuberculosis
- Chronic Granulomatous inflammation
- Can be caused by: schistosoma ova,
mycobacterium tuberculosis or leprae
(tuberculous form of leprosy)
- BUT an infection with
mycobacterium can cause a
granuloma seen in the CENTER
- Fungal infection or syphilis

Enzymatic Fat Necrosis

- Ex. in the fat cells of the omentum
due to inflammation and destruction
of the pancreas
Pancreas: endocrine and
exocrine function, usually
excretes enzymes in proactive
form
- Has their own duct system
Alcohol intake causes
spasm of the pancreatic
ducts
Ducts close off and
enzymes build up in the
pancreas > become
activated
- Spillage of pancreatic juice
into the other structures in the
omentum digests the lipid
content in the omental
connective tissue
Lipids are saponified by the
enzymes
- Probable sites may be
anything near the pancreas
Ex. breast tissue undergo traumatic fat necrosis

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First Shift PATHOLOGY First Cluster Exam

Cytoplasmic Changes Pathologic Calcification

- Cellular swelling - Dystrophic Calcification
In sublethal injury Alterations in areas of previous necrosis
Reversible Can be intracellular or extracellular or both
Ex. hypoxic kidney tubules Previous injury to tissues
- Fatty change or steatosis Ex. Psammona bodies seen in papillary
Seen in the liver carcinoma of the thyroid, meningioma, serous
D/t alcohol, malnutrition, drugs carcinomas
Accumulation of triglycerides that fill vacuoles Ex. in atherosclerosis complicated by
(Lipid vacuoles) calcification
- Not able to utilize fats, stored in the body > Ex. in aging and damaged heart valves
tunica intima of the blood vessels and in the complicated by calficication
hepatocytes - Metastatic Calcification
Reversible change: limiting fat ingestion and In normal tissues whenever there is
formation, exercise, intake of drugs are lipolytic hypercalcemia
(statins) Associated with hyperparathyroidism, Vit. D
- Inclusion (pigments) intoxication, systemic sarcoidosis, milk-alkali
Carbon (black) syndrome, hyperthyroidism, Addisons disease,
- Exogenous pigment increased bone catabolism (tumors),
- In lungs of people living in polluted areas immobilization
- Carbon will be engulfed > macrophages
cannot digest > become residual bodies References:
and are deposited and in the hilar lymph - Patho Lecture (Dra. Santos)
nodes - Robbins (pictures)
Ex. anthracosis in a coal miner inhaling
coal dust
Hemosiderin, Bilirubin, Lipofuscin, Melanin (all
brownish)
- These are endogenous pigments
- Hemosiderin from breakdown of RBCs
Bilirubin from gall bladder
Lipofuschin wear and tear pigment
Melanin in skin
- Proteins
Reabsorption droplets in proximal renal tubules
Russell bodies (immunoglobulins in plasma cells
Alpha-1 Antitrypsin in liver cells
Glycogen (in diabetes mellitus)
- Carbohydrates
- Tattoo ink (exogenous)

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