HISTOPATHOLOGY LEC

LECTURE 1: CELLULAR ADAPTATIONS PART 1

FRANCIS IAN L, SALAVER, RMT, MD
JUNE 6, 2021
For updates and corrections → @mar4rii on Twitter

- If the normal tissue is acted upon by an injurious stimuli, the

cells will respond to adapt, once the cells adapt, the cells
I. CELLULAR ADAPTATION
will become stable.
- All of these adaptations will eventually become reversible if
there is a removal of injurious stimuli/cause and will
eventually go back to their normal state.

Definition
● Not all cellular adaptations need to be caused by injurious
agents. Sometimes they are physiological processes.
● Cells must always adapt, even under normal conditions, to
changes in their environment
● Example:
○ Enlargement of uterus to accommodate the
growing fetus
○ Enlargement of muscle mass due to weightlifting
in the gym
A. Atrophy
- If the cell will be stressed, it will try to adapt in response ● Reduction of the number and size of parenchymal cells of
to the presence of the stress. Thus, the cell will have an organ or its parts which was once normal.
changes in its organelles, cytoplasm, and cell ● 2 Types:
○ PHYSIOLOGIC
membrane.
■ Aging
- If the injury will progress, and the cell cannot anymore ■ Gonads after menopause
adapt to it, the cell will die = Necrosis ○ PATHOLOGIC
- As long as the cell can adapt to the presence of the ■ Caused by underlying disease
stressors and injurious agent, the cell will continuously
live.
- If the stressor and injurious agents are removed, that
cell will eventually go back to being normal. = Recovery
- The cells in our body, as long as they can withstand
stressors and injurious agents, can actually adapt to
them. If not, they will end up dying.
a. Cellular Injury
● Occurs if the cells fail to adapt in the presence of a stimuli

a. Physiologic Atrophy
● Can be due to normal process of aging and loss of
endocrine stimulation
1. Thyroglossal duct after birth
2. Atrophy of the thymus during puberty
b. Cellular Adaptations 3. Atrophy of the gonads after menopause
● Reversible changes in the size, number, metabolic activity - Decrease levels of estrogen and some organs
and functions of cells in response to changes in their that are dependent to estrogen will decrease their
environment.. size and cells
● Needs to be reversible, if not it will end up to cellular injury 4. Atrophy of the brain with aging
● Adaptations may take several distinct forms: 5. Sarcopenia
○ Atrophy
○ Hypertrophy 1. Thyroid Embryology
○ Hyperplasia
○ Metaplasia

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 ● It embryologically originated from the base of the tongue
● Thyroid develops from the tongue and it will migrate
downwards to the anterior neck.
● As it do so, it forms a duct which connects it to the base of
the tongue, the duct is called thyroglossal duct
● As the fetus will reach 7 weeks of life intrauterine, that
ducts should undergo physiological atrophy
● Check number 4
● Thyroglossal duct, due to unknown mechanism, will
undergo atrophy at the 7th week of intrauterine life.
● Failure of atrophy process will cause persistence of the
thyroglossal duct
● Food particles and fluid can enter the duct, forms a cyst or
enlargement of the thyroglossal duct and cause infection.
Surgical removal is required.
Failure of the thyroglossal duct to undergo atrophy
● Can develop thyroid carcinoma
Wach https://www.youtube.com/watch?v=dhfoDsaCph8 start 0:44
- 2 types of lymphocytes = T cells & B cells (produced in
the bone marrow)
- RED ARROW = B cell → matures in the bone marrow
- BLUE ARROW = T cell → has to leave the bone marrow
and go to the thymus to reach maturation
2. Thymus Atrophy
● Can be found in the mediastinum of the chest
● Compare the size of the thymus of a fetus (infant/child) to
an adult
○ Infant = bigger thymus
● Thymus undergoes involution or atrophy during puberty.
● Unknown reason but some studies are suggesting that
testosterone and estrogen have something to do with the
atrophy
● Thymus are the site of maturation for T cells
● We can longer produce T cells after puberty, that's why
people living with HIV cannot replace the T cells destroyed
by the virus thus they become immunocompromised.
Appreciate the thymus in adults, majority of the cells were
replaced by fats
3. Atrophy of the brain with aging
Compare the spaces between gyri. Larger spaces means there was
a reduction in the size of the brain.
2

● Brain undergoes physiological atrophy upon aging
● Right = The gyri of the brain had reduced in sizes creating
bigger spaces between them
1. Starvation atrophy
● Occurs due to the depletion of carbohydrates and fats then
followed by protein catabolism
● Carbohydrates = main source of energy
● If we starve the body, we will look for alternative sources of
energy; Body will first break down the fats, followed by the
proteins.
● Proteins are an essential part of muscles.
● People who have already depleted their carbohydrate and
fat reserves will start breaking down their proteins in their
muscles, and the muscles will undergo atrophy.
● Example:
○ Cachexia seen in cancer and severely ill patients
Cachexia as example of starvation atrophy

4. Vaginal atrophy in postmenopausal state

Why do you think cachexia/starvation atrophy will happen to

● Since there is lack of estrogen in the menopausal stage,
the vagina undergoes atrophy causing loss of elasticity and
lubrication
● Main cause why menopausal women report pain during sex
5. Sarcopenia
people with cancer?
1. Bedridden = cannot stand up and get food
2. Poor appetite = don’t eat carbohydrates
3. Lots of chemotherapeutic drugs = side effects such as
vomiting and loss of appetite
4. They have cancer = tumor cells are rapidly dividing and
will demand energy. The body will feed them energy by
breaking down proteins.
Cachexia
● is a “wasting” disorder that causes extreme weight loss and
muscle wasting, and can include loss of body fat.
● Stored glycogen and fats are first metabolized
● Proteins in muscles are metabolized after the glycogen and
fats causing muscle wasting
● Loss of more than 5 percent of the body weight over 12
months or less, when patient is not trying to lose weight

● Type of muscle atrophy that occurs with aging and/or Normal skeletal muscles (left) have almost the same sizes on cross
immobility. It is characterized by the degenerative loss of section. The picture on the right is showing significant differences in
skeletal muscle mass, quality, and strength. the sizes of the muscle fibers
● Common among senior citizens
○ As they grow old, u can see there is a reduction in 2. Ischaemic atrophy
the sizes of their muscles ● Ischemia = reduction in the blood supply of the organ
● Decline in activity ○ One of the possible causes is the formation of
● Nutrition atheroslerotic plaque
● Increasing resistance to growth factors ● Gradual diminution of blood supply due to the
atherosclerosis results in the shrinkage of the affected
b. Pathologic Atrophy organ.
● If the atrophy is associated with an underlying medical
condition
1. Starvation atrophy
2. Ischaemic atrophy
3. Disuse atrophy
4. Neuropathic atrophy
5. Endocrine atrophy
6. Pressure atrophy
7. Idiopathic atrophy

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Atherosclerosis due to hypertension and hypercholesterolemia cells to die and if the cells will rupture, the cell will
causing narrowing of lumen of blood vessel release the newly formed polio virus in the blood
- This virus will be transported by the blood towards
the central nervous system

- Having high levels of low density lipoprotein (LDL) will

cause the deposition of cholesterol molecules on the tunica
intima (inner layer of blood vessel) and will trigger
inflammation.
- With the onset of inflammation, the area will become
swollen and there will be deposition of calcium and will
harden causing the lumen of the blood vessel narrowed.
- If it is narrowed, there would be reduction in the blood
supply of the organ and will not receive enough oxygen.
- So, the cells there will undergo atrophy resulting in the
decrease of the size of the organ.
- Polio viruses trying to invade the nerve cells
Compare these two kidneys

- Polio viruses are known to kill neurons

- The organs that are innervated by these neurons will have
loss or diminished functions
- Mostly affect the neurons controlling the skeletal muscle
- The person will not able to move their muscle and
later undergo atrophy
- Somewhat related with disuse atrophy

Surgically removed from the same individual

3. Disuse atrophy
● Disuse atrophy occurs when an organ is no longer as active
as usual.
● For example: Stroke patient with right sided weakness will
have disuse atrophy of the muscle on right upper and lower
extremities
○ She will rely on her left arm and left leg for
movement and will not anymore use her right arm
and right leg causing it to undergo atrophy Patients with polio
Accident, stroke, major surgical procedures

4. Neuropathic atrophy
● Problems or disorders in the nerves causing loss or
diminished functions of the organ they are controlling.
5. Endocrine atrophy
● Example: Poliomyelitis
- Transmitted through fecal-oral route ● Imbalances in the level of hormones in the body
- Once they are inside the intestinal cells, they will ● Decreased synthesis of the hormones leads to the atrophy
multiply in number and will cause the intestinal of the organs it is stimulating

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 ● Example: Hypopituitarism causes atrophy of the gonads, ● Example: a man is taking steroids because he wants to
thyroid gland and adrenal gland increase his muscle mass
● Most steroid supplements bodybuilders take have
Anterior pituitary gland controls other gland such as thyroid testosterone content
(TSH), Adrenal cortex (ACTH) and gonads (FSH and LH)

- Pituitary gland is referred to as the master gland of the

body because the anterior lobe controls other endocrine
glands
○ Normal physiology of production of testosterone
- Can control the function of thyroid, testis, overy, adrenal
■ Decrease of testosterone level in the
cortex
body will be sensed by the
- Imagine a case of pituitary tumor, tumor has already
hypothalamus producing GnRH
replaced the normal cells of the pituitary gland.
■ GnRH will stimulate the anterior pituitary
- The pituitary gland cannot anymore:
gland to produce FSH and LH
- produce thyroid stimulating hormone thereby the
■ LH will act on the Leydig cells to
thyroid will no longer be activated.
produce testosterone
- Stop producing ACTH = the adrenal will no longer
■ Enough levels of testosterone will send
be stimulated to release cortisol
a negative feedback to the pituitary and
- Will stop producing FSH and LH
hypothalamus to stop producing GnRH
- Decreased synthesis of these hormones will eventually
and LH
cause the atrophy of the hormones from the anterior
○ If a person is taking steroid supplements rich in
pituitary gland
testosterone
- Expect to find atrophy of the gondas, thyroid gland, and
■ Additional testosterone will suppress to
adrenal gland
the pituitary gland and hypothalamus to
stop producing GnRH and LH
Hypopituitarism
● Since most anabolic steroids contain testosterone, the
blood testosterone level in the blood will become high.
● Testes will stop producing testosterone
○ No LH to respond to
○ Undergoes Atrophy
● Decreased activity of the testes will lead to their atrophy.
● Testicular atrophy due to excessive steroid intake

● Anterior pituitary gland controls other glands such as

thyroid (TSH), Adrenal cortex (ACTH) and gonads (FSH
and LH).
● Without the hormones coming the pituitary gland, the 6. Pressure atrophy
glands it is controlling will undergo atrophy ● The wasting of hard or soft tissue resulting from excessive
pressure
Atrophy of the breast ● Ex. tumor compressing organ such as brain, kidney and
● due to decreased estrogen levels liver
● Estrogen production is decreased in menopause
● Estrogen is derived from cholesterol so anorexia nervosa
can cause atrophy of the breast. Cholesterol is derived from
the diet
● Physiologic type because of its relation to aging
○ Instances where it can be associated to a
pathologic condition: anorexia nervosa
■ Conscious of physical appearance,
stimulates gag reflex to vomit food
causing decrease of nutrient supply in
the body
■ Body will look for other sources of
energy: cholesterol
■ Used up cholesterol, the body won't ● Optic nerve - detection of light
form estrogen (atrophy of the breast) ○ Right and left optic nerve will cross in the center
to form the optic chiasm
Next type of endocrine atrophy can be caused by: ○ Red arrow: optic chiasm
● Excessive amount of hormone in the body due to intake ○ Found superior to the pituitary gland
of hormonal supplements
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 ■ Due to the increase in the sizes
(hypertrophy) and number (hyperplasia)
of cells

● Coronal cut section: Appreciate the location of the optic

chiasm in relation to the pituitary gland

○ Red arrow: lower segment of uterus of non

pregnant woman
○ Blue arrow: lower segment of uterus of a pregnant
woman

● Red square: Growing pituitary tumor compressing optic

chiasm causing its atrophy eventually causing patient to
develop blindness

● Uterus has 3 layers:

○ Endometrium - innermost, where
embryo is implanted, with glands and
blood vessels
○ Myometrium - thickest, smooth muscles
7. Idiopathic atrophy that contract to assist in labor
● Atrophy of unknown cause ○ Perimetrium - outermost
● If after thorough investigation and test, the cause of atrophy
is difficult to identify, it is classified as idiopathic atrophy.

B. Hypertrophy
● Increased in the size of parenchymal cells resulting to the
enlargement of the organ or tissue without any change in
the number of cells
○ Increased in number of cells = hyperplasia
● Two types: Physiologic and pathologic

● Picture taken from the myometrium of the uterus

● Picture B: smooth muscles of non pregnant
woman
○ Spindle shaped smooth muscles
● Picture C: smooth muscles of a pregnant woman
○ Muscles increase in size during
pregnancy (hypertrophy)
● Enlargement of uterus is a combination of both
hypertrophy and hyperplasia

● Example 2: Bodybuilding
○ Bodybuilding causes the muscles to increase in
Physiologic Hypertrophy size
● Increase in the sizes of cells due to physiologic demand or ○ Increase the sizes of muscle fibers
most of the time by endocrine stimulation
● Good example 1: enlargement of uterus during pregnancy Pathologic Hypertrophy
to accommodate growing size of fetus (though enlargement ● Increase in size of the cells or organ in response to a
of the uterus is both caused by hypertrophy and disease or pathologic condition
hyperplasia) ○ Pathologic ventricular hypertrophy
○ Uterus is a pelvic organ but extend to become an ○ Clitoral hypertrophy
abdominal organ during pregnancy

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 ● Normal Blood Circulation ■ Zona glomerulosa, cholesterol will be
○ If a person has hypertension, the pressure outside modified to produce aldosterone
the heart is higher than normal so the ventricle ■ Zona reticularis, cholesterol will be
has to increase its power just to deliver the same modified to produce androstenedione
amount of blood to the organs
■ Uncontrolled hypertension
■ Pressure in the arteries and peripheral
blood vessels
■ Left ventricle has to double its efforts to
pump blood out of the heart to aorta due
to higher pressure outside the heart
■ Cardiac muscles of LV will increase in
size to be more powerful
■ Causes left ventricular hypertrophy
● Cardiomegaly: enlargement of
heart
○ If this will persist, the muscles of the ventricle will
undergo hypertrophy

● Congenital adrenal hyperplasia

○ Absence of 21-hydroxylase enzyme
■ 21-hydroxylase is important in the
processing of cholesterol in zona
● Cardiac muscles increase their sizes just to pump fasciculata and glomerulosa
blood out from the heart towards the aorta against ● Absence will make cholesterol
the increased blood pressure in the systemic no longer be converted in
circulation fasciculata and glomerulosa
● Outcome: cholesterol will be
Normal heart vs Heart with Ventricular Hypertrophy processed by reticularis =
increased production of
androstenedione (male sex
hormones)

● Adrenal gland
● Red circle (aldosterone) under the microscope

● Left: longitudinal cut section of cardiac muscle

○ Striated, branched, central, single nuclei
● Right: cardiac muscles are bigger because of left
ventricular hypertrophy

Adrenal gland has 2 regions

○ Zona reticularis appears darker
● Adrenal medulla
● Adrenal cortex has zona glomerulosa, fasciculata and
Normal adrenal cortex
reticularis
A - Glomerulosa
○ Produces specific hormones
B - Fasciculata
■ Aldosterone (glomerulosa)
C - Reticularis
■ Cortisol (fasciculata)
Congenital adrenal hyperplasia,
■ Androgen (reticularis)
cells of A & B are not functional
○ All of the hormones are derived from cholesterol
(can't convert cholesterol),
■ If cholesterol is in the zona fasciculata, it
diverted towards cells of
will be chemically modified to produce
reticularis = overproduction of
cortisol and corticosterone
male sex hormone
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 C. Hyperplasia
● Is the increase in the number of parenchymal cells
resulting to the enlargement of the organ
● Quite often, both hyperplasia and hypertrophy occur
together
● Can also be physiologic or pathologic

Physiologic Hyperplasia
● Can be due to hormonal stimulation
○ Ex. increase in estrogen can cause proliferation of
cells of the mammary gland during puberty or in
● Adrenal gland from someone with congenital adrenal pregnancy
hyperplasia ○ Hormonal stimulation of uterus during pregnancy
● Expanded zona reticularis (dark stained) ● Can be due to compensation
○ Increase in number of cells ○ Removal of right kidney → hyperplasia and
hypertrophy left kidney
Image of a female infant with congenital adrenal hyperplasia and ○ Removal of right lobe of liver → hyperplasia of the
high androgen levels, clitoris will be enlarged cause of the effect of left lobe
androgens
Breasts are composed of mammary glands (Right photo: Breast
of a child)

● Leads to clitoromegaly

Genital area/ Normal (MALE)

● Mammary glands of a child
○ Few ducts and glands embedded in the CT

● Newborn genitalia: scrotum (contains testis), penis

● Mammary gland of an adult female

○ Increase of number of ducts and glands
■ Increase in number of cells due to
presence of estrogen
■ Physiologic hyperplasia

Removal of right lobe of the liver causes the left lobe to undergo
hyperplastic change for compensation

● Clitoris of female with congenital adrenal hyperplasia, will

have enlarged clitoris looking like the glands penis of males
○ Increased of size, this is a case of hypertrophy
● Adrenal gland = hyperplasia (increased NUMBER of cells in
zona reticularis)
● Clitoromegaly = hypertrophy (increased SIZE)
● Labia will attempt to fuse together to form scrotum

Compensated Hypertrophy
● Occurs when in organ when the contralateral organ is
removed
● Example: Patient X donated her right kidney to her younger
sister. The left kidney may increase in size to compensate ● Left lobe of liver will try to replace the right lobe
for the loss of the right kidney ○ Hepatocytes of the left lobe will increase in
number
○ Hyperplasia

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Pathologic Hyperplasia Benign prostatic hyperplasia
● Occurs in response to a disease or pathologic condition or
persistence of injury or stimuli
● Examples:
○ Callus formation in the skin due to irritation or
warts formation
■ Warts caused by human papillomavirus
○ Benign prostatic hyperplasia -- due to the effects
of excessive male hormone

Callus formation in the skin due to constant irritation or energy

● Below the urinary bladder is the prostate gland

● Central portion: first portion of the urethra called prostatic
urethra (enveloped by prostate)
○ Urine will drain from the urinary bladder to the
prostatic urethra
● There are males whos prostate gland cells are very
sensitive to testosterone
○ Cells will increase in number causing prostate
gland to increase in size
○ With the increased in size of the prostate gland, it
may compress the prostatic urethra
○ The male with benign prostatic hyperplasia, will
have difficulty in urinating

Prostate surrounds the prostatic portion of the urethra thus if

the prostate enlarges, it can cause obstruction
● Patient will have difficulty in urination
● Women who wear high heels at work would have pressure
points on their feet
○ Constant exposure of cells to pressure = cells will
compensate and increase in number
○ Leads to callus formation

Warts caused by Human papilloma virus -- the virus can cause

focal hyperplasia of skin cells

Benign prostatic hyperplasia is caused by increased stimulation

of the prostate glands by testosterone causing them to multiply
in number

Normal skin vs Warts

● The epidermis of the skin with warts is thicker due to the
hyperplasia of cells Normal prostate

● Glands surrounded by the fibromuscular stroma (pink

● Left side: Normal skin under the microscope colored)
○ Epidermis is lined by stratified squamous ○ Surrounds the individual glands of the prostate
epithelium
● Right side: wart
○ Thickening of epidermal layer of skin due to
increase number of the cells
○ Pathologic hyperplasia

● Prostate glands are lined by single layer of cells

● In Benign prostatic hyperplasia, the lines are doubled
○ Cells multiplied (hyperplasia)

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Benign prostatic hyperplasia

● Glands are covered with 2 layers of cells

Normal prostate vs. Benign prostatic hyperplasia

● Left photo: Normal prostate

● Right photo: Benign prostatic hyperplasia
○ Increase in number of cells

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 HISTOPATHOLOGY LEC

LECTURE #: CELLULAR ADAPTATIONS PART 2

FRANCIS IAN L, SALAVER, RMT, MD
JUNE 7, 2021
For updates and corrections → @mar4rii on Twitter

I. CELLULAR ADAPTATIONS - If not removed, metaplasia may progress to cancer

Review: changes that occur in cells when they are (neoplasia)
presented with stressors or injurious stimuli. But these changes
should be reversible, meaning if the injurious stimuli and the a. Epithelial Metaplasia
stressor will be removed, the cells should be able to return back 1. Squamous Metaplasia
to its normal state. - Pseudostratified ciliated columnar epithelium of the
bronchi is replaced by stratified squamous due to the
Reversible changes in the size, number, metabolic activity damaging chemicals present in cigarettes
and functions of cells in response to changes in their - The purpose of this type of metaplasia is to protect the
environment.. airway from the cigarette content
Adaptations may take several distinct forms: - this type of metaplasia is caused by chronic exposure to
- Atrophy the chemicals of the cigarette.
- Hypertrophy
- Hyperplasia
- Metaplasia
D. Metaplasia
- Reversible changes in one type of epithelium cells to
another adult epithelium
- Usually a response to abnormal stimuli
- Often reverts bark to normal on removal of stimulus
- Just like in the case of atrophy, hypertrophy and
hyperplasia, the changes that will happen in metaplasia
is also reversible.
- But what changes can we see in metaplasia? Take note,
in metaplasia there is a change from one mature
epithelium to another mature or normal epithelium.
- It’s like saying, an organ that is lined by simple
squamous epithelium will change its lining epithelium
from simple squamous to simple columnar.
- If the lining epithelium will be replaced by an
ABNORMAL one, that is already a state of NEOPLASIA
or CANCER.
- Metaplasia is a step away from Neoplasia.
- The pseudo. Strat. Ciliated columnar epithelium of the
airway is designed to have a cilia to propel the mucous
and the trapped bacteria in the mucous out from the
body, but if there’s chronic exposure to the harmful
chemicals that are present in the cigarettes, the pseudo.
Strat. Ciliated columnar cannot anymore protect the
airway.
- The respiratory organ will adapt by changing the
psedo.strat. ciliated columnar epithelium into stratified
squamous epithelium.

If that organ will be exposed to an injurious stimulus or a stressor,

the organ will try to protect itself by replacing the simple columnar
epithelium by a stratified squamous epithelium because the
organ thinks that stat. squam would better protect it from the
presence of the stressors or injurious stimuli.
- Metaplasia is a usual response to abnormal stimuli but
once the stimuli will be removed, the cells or the lining
epithelium will revert back to normal.
Important points to take note about
metaplasia
- Adaptive response in which cells sensitive to a particular
stress are replaced by more resistant cell type
- Metaplastic tissue returns to normal is the cause is
removed
1
RIGHT: closer look of the lining epithelium of the bronchus:
PSUEDOSTRATIFIED CILIATED COLUMNAR EPITHELIUM.
- If the bronchus will be chronically exposed to the
harmful contents of the cigarette, the pseudo.strat,
ciliated columnar epithelium on the LEFT side will be
slowly replaced by the stratified squamous on the
RIGHT side.
- Since the pseudo.strat, ciliated columnar epithelium is
replaced by stratified squamous then we will refer to this
as a case SQUAMOUS METAPLASIA.
- PSEUDOSTRATIFIED CILIATED COLUMNAR🡪
STRATIFIED SQUAMOUS = SQUAMOUS
METAPLASIA

GASTROESOPHAGEAL JUNCTION
REVIEW: Esophagus- stratified squamous non-keratinized A portion of the esophagus now has simple columnar epithelium
epithelium similar to that of the stomach—COLUMNAR METAPLASIA
Stomach, S.I, and L.I- simple columnar epithelium 3. Urothelial Squamous Metaplasia
Junction between Stomach and esophagus- transition of lining
epithelium from stratified squamous to simple columnar
epithelium

Stomach simple columnar Esophagus – stratified squamous

RIGHT: Esophagus Schistosoma haematobium
LEFT: Stomach - MOT: skin penetration
2. Columnar Metaplasia
- Replacement of the stratified squamous epithelium of
the esophagus by the simple columnar epithelium
similar to the stomach
- This is to protect the esophagus from the
acid = commonly seen in people with chronic GERD
- Should there be a reflux of the acid content of the
stomach towards the esophagus, there would be an
accompanying tissue destruction.
- If the reflux of the acid would occur CHRONICALLY, - If you have thousands of these in the urinary bladder,
meaning the esophagus is always exposed to the acid they can actually cause injury to the transitional
content of the stomach, the esophagus will try to change epithelium of the urinary bladder. Aside from the fact
its lining epithelium to the SAME lining epithelium of that that the adults can also produce chemicals that can
of the stomach in order to protect itself from acid. irritate the transitional epithelium of the urinary bladder.
- STRATIFIED SQUAMOUS 🡪 SIMPLE COLUMNAR - Since transitional epithelium is designed for the organ to
COLUMNAR METAPLASIA stretch and NOT to protect the organ, the urinary
- epithelium of the stomach = COLUMNAR bladder due to CHRONIC Schistosoma haematobium
METAPLASIA infection will eventually undergo metaplasia.

2
 - Urinary bladder will replace the transitional epithelium
with stratified squamous that can best protect the
urinary bladder from the injury caused by the eggs and
chemicals released by the adult Schistosoma
haematobium.
- TRANSITIONAL EPITHELIUM 🡪 STRATIFIED
SQUAMOUS = UROTHELIAL SQUAMOUS
METAPLASIA
- Due to the chronic injury caused by urinary stones or
chronic infection with Schistosoma haematobium
MECHANISM
How can the organs in the body change their lining
epithelium?
Can be seen in the ff conditions
- Rheumatic fever
- Atherosclerotic plaque formation
- Breast cancer
- Toxoplasmosis
- Rheumatic fever – Streptococcus pyogenes
Tonsillitis
- Caused by bacteria Streptococcus pyogenes
- Has a certain chemical in its body- M PROTEIN
- M PROTEIN: looks similar to a certain chemical antigen
that we can find in our heart valves.

- If you develop infection with streptococcus pyogenes,

you produce antibodies against its M PROTEIN.
- If a person will be repeatedly exposed to streptococcus
pyogenes cause of recurring tonsilitis, the more that
they will be exposed to streptococcus pyogenes,
- Epithelium has STEM CELLS; found on the lower most
particularly its M protein, the HIGHER the antibodies
layers of the cells.
that they will form.
- If there’s a constant presence of an injurious stimuli,
- With a certain amount of antibodies to M proteins, some
these stem cells will no longer give rise to the former
of the antibodies now will start attacking the heart
epithelial cells of the organ. Instead, that stem cell will
valves.
adapt and form a NEW type of lining epithelium.
PATHOLOGIC CALCIFICATIONS
- Deposition of calcium salts in tissues other than the
osteoid (bone matrix) and enamel
- Can be classified as: Dystrophic or Metastatic
- If the calcium is deposited somewhere else, then it is
now referred to as pathologic calcification.
Dystrophic Calcification
- Macroscopic deposition of calcium in dead or
degenerated (injured) tissue
- Will ONLY happen if there is a presence of damage or
injury.
● THERE SHOULD BE THE PRESENCE OF
DAMAGE/INJURY
- Represents extracellular deposition of calcium from
blood or interstitial fluid If the heart valves become damaged or injured you will now call it
● Often visible to the naked eye which can RHEUMATIC FEVER.
appear as gritty sand like grains to firm rock Rheumatic Fever
material. - Is a complication of recurring tonsilitis brought about by
Streptococcus pyogenes.
Normal heart valves vs Dystrophic calcification of heart valves
seen in rheumatic fever

LEFT: NORMAL
- Heart valves will be targeted by the antibodies of the
BLUE ARROW: on those areas of injury, calcium will be
patient and if they are targeted by the antibodies and
deposited. Those areas appear to be sandy in appearance or
they may appear like firm rock material.
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 most likely they will undergo IMMUNE MEDIATED
destruction
- Those areas that were attacked by the antibodies will
undergo calcification.
LEFT: Normal heart valves
RIGHT: Heart valves with Dystrophic calcification
Calcium appears BLACK under H and E normal heart valves vs
heart valves with calcification
LEFT: NORMAL
RIGHT: already attacked by the antibodies against the M Protein
of the Streptococcus pyogenes.
- Area with the black color represents the site for the
deposition of calcium.
Atherosclerosis
- Cholesterol in the blood is deposited in the walls of the
arteries
- Presence of cholesterol recruits monocytes to the areas
- Result from having HIGH low density lipoprotein (LDL)
or high levels of cholesterol in the blood.
- The LDL will deposit the cholesterol into the TUNICA
INTIMA of the arteries.
- As the monocytes or macrophages engulf the deposited
fats, they also release chemicals which cause damage
to the tissues of the blood vessels.
- These damaged areas will soon undergo calcification
thereby causing the plaque to harden
- Atherosclerosis
- Normal artery Calcium under H and E appears black in
color
- Since the cholesterol is foreign to the tunica intima of
the arteries, it will actually trigger the immune system.
- The immune system will react by sending monocytes
and macrophages to the area where the cholesterol
molecules were deposited.
- They will try to clear the cholesterol by engulfing them in
the process called phagocytosis.
- PROBLEM: as they are performing phagocytosis, these
monocytes and macrophages are releasing chemicals
and these chemicals can actually cause local damage to
the arteries.
- Since there are areas of damage or injury to the wall of
the artery, since there is blood flowing through it, the
calcium in the blood will slowly deposit on the areas of
damage causing now the area where the cholesterol
molecules were deposited to calcify.
- The calcification and the deposition of the cholesterol
will cause the formation of atherosclerotic plaque
NORMAL ARTERY
- Easily identified from veins because it has a thick layer
of smooth muscles.
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 ● Oocyst - passed out from the infected stool of the cat
and would undergo sporulation
Sporulation/Sporogony
- Oocyst will produce sporozoites inside

● If oocysts are ingested by humans, it will rupture and

ARTERY WITH ATHEROSCLEROTIC PLAQUE AND
CALCIFICATIONS
- Calcium under H and E appears BLACK in color.
- Areas that appear black are the areas where calcium
ions were deposited.
- Since this one occurred AFTER the damage caused by
recruited monocytes and macrophages in the area
where the cholesterol molecules were recruited, so this
type of calcification is DYSTROPHIC.
Toxoplasmosis
release sporozoites, eventually affecting the human
intestine
● Sporozoites will transform to tachyzoites
● Tachyzoites will invade monocytes in blood or
macrophages in tissue
● Tachyzoites will multiply rapidly
● Once the immune system is activated, tachyzoites will
transform to bradyzoites
● Bradyzoites replicate slow therefore the immune system
will not be able to locate them
● Bradyzoites will enclose themselves in a cyst
● One of the organs to where the bradyzoites will form
cysts is the brain
● Brain tissues will be destroyed and will undergo
calcification
- When transforming into cysts, they damage tissue to be
able to occupy space
- The area of damage will now have calcifications

- Caused by Toxoplasma gondii

- Definitive host: Cat

- Bones appear white in x-rays bcos they have calcium

Calcium is radiopaque thus it will appear white with radio

imaging (bone in Chest X-ray)
● Appreciate the cyst of Toxoplasma gondii bradyzoites
● Check the calcified area around the cyst.

● Once humans become infected with Toxoplasma gondii,

the parasites replicates initially as tachyzoites in the
intestine
● As they transfer to other tissues in the body, they
transform into bradyzoites enclosed within the cyst
- White ring = presence of calcium
5
 - Calcium because of damage ■ Vitamin D enhances the absorption of
- Ring because it is a cyst formed by the bradyzoites of calcium form the food
toxoplasma gondii ■ Higher levels of vit D, more calcium
Breast Cancer absorbed
- Dystrophic calcification can also happen in cases of ○ Hyperparathyroidism
cancer because the immune system tries to kill them ■ Parathyroid hormone increases blood
- Such have a corresponding damage calcium level
- Deposition of calcium in areas of cancer cells ■ Tumor in the parathyroid gland that
produces high amount of parathyroid
gland will result in high blood calcium
level
○ Renal failure
○ Destruction of bone by tumors – causing
leakage of calcium into the blood
■ Therefore calcium will be deposited in
tissues
VITAMIN D SYNTHESIS

● Tumor cells are killed by the immune cells and these

cells will undergo calcification which can be seen in
radioimaging procedures

Radiographic image of breast cancer: - Exposure to the sun helps produce vit D
- Best time of exposure: 8am - 10am
- Exposure beyond that time increases the risk
of skin cancer
1. Cholesterol underneath the skin will be converted to
7-Dehydrocholesterol -- inactive form of vitamin D
2. 7-Dehydrocholesterol will be transported to the liver and
undergo hydroxylation; liver will add 1 OH group,
converting it to 25-hydroxyvitamin D3 (OH was added to
the 25th carbon)
3. Transported to the kidneys and becomes 1,
25-dihydroxyvitamin D3 (active form)

- If the person has renal failure, the kidney cannot

hydroxylate 25-hydroxyvitamin D3 = Vitamin D
deficiency

Vitamin D and Parathyroid hormone activities

- Function to increase blood calcium level

- White colored areas = calcium

- Presence of calcification in the breast would indicate the
possibility of cancer

Metastatic Calcification
● Calcium is deposited in the tissue not because there is
pre existing damage but because the calcium level of
the blood is so high, that some calcium are deposited in
tissues
● Reflects a deranged calcium metabolism
Increased Vitamin D due to excessive intake Increased PTH
● Associated with increased calcium concentration in the
due to tumor in parathyroid gland
serum or blood
- Vitamin D Toxicity
● Any condition that can increase calcium level in the
- Too much vitamin D in the body
blood leads to calcification in inappropriate locations
- Excess calcium will be deposited in other
● Can be seen in
tissues
○ Vitamin D toxicity = Vitamin D increases
calcium absorption from the diet

6
 ● Cancer may arise from bone or may metastasize to the
bone from other organs shown in the photo..
● Tumors destroy bone causing the calcium to leak into
the blood leading to metastatic calcifications
Excessive calcium can deposit in the lungs Normal alveoli
vs alveoli with calcifications

Vitamin D requires the kidney to become active Renal failure

causes lowered blood Vitamin D level
- Kidney can no longer hydroxylate 25-hydroxyvitamin D3
- Blood calcium of this patient will go down because of
vitamin D deficiency

- Normal appearance of alveoli

Decreased Vit D causes the parathyroid gland to

compensate by increasing PTH level
- PTH increases calcium levels

Bone Tumors

- Black deposits around normal alveoli are calcium

Autophagy
● Phagy = eating
● Phagocytosis
○ Engulfing of bacteria by WBCs
● Auto = self
● Autophagy
○ “Self eating”
○ Cell destroys its own component
○ Source of nutrients
○ Organelle is damaged
● Normal physiological process in the body that deals with
the destruction of cells in the body
● Maintains homeostasis protein degradation and turnover
of destroyed cell organelles to form new ones.
● Defends cells against metabolic stress
○ Nutrient deprivation
■ Cell will break down one of its
components with proteins

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 ■ Breakdown of proteins will produce
amino acids thus will be used to
produce energy
○ Growth factor deprivation
○ Hypoxia

○ Breakdown of the proteins within the cell will be

broken down through autophagy to generate
amino acids to generate energy
● Works as a cellular housekeeper ● Damaged organelles and defective or abnormal proteins
○ Removal of damaged organelles are enclosed first in a vesicle before it is digested by the
○ Removal of defective protein which does not lysosomes
contribute to the function of the cell to form
useful proteins
○ Removal of abnormal protein which may cause
mutations and cancer formation

Steps in Macroautophagy

- Damaged organelles are enclosed with an isolation

membrane
- This membrane will form the vesicle = autophagosome
1. Presence of the stimuli causes of the phagophore
(isolation membrane. Isolation membrane encloses the
● Can occur in three ways targeted protein or damaged organelle).
○ (1) Microautophagy 2. Autophagosome formation
○ (2) Macroautophagy 3. Autophagosome fuses with the lysosomes
○ (3) Chaperone-mediated autophagy 4. Digestion
a. Microautophagy
c. Chaperone-Mediated Autophagy

● Lysosome - organelle responsible for digestion

● Damaged organelles and defective or abnormal proteins
● Specific proteins are identified by chaperones (example
are directly engulfed by the lysosome then degraded
Heat Shock protein) and is then carried towards the
● Happens if a damaged organelle, an abnormal or
lysosome for degradation
misfolded protein, are directly engulfed by the
● Heat shock protein
lysosomes and are degraded inside the lysosomes
○ Looks for abnormal or nonfunctional protein
○ Acts as the chaperone towards the lysosome
for digestion

b. Macroautophagy

● Macroautophagy is activated as early as 30 minutes into

starvation and remains at high activity for at least 4–8
hours into starvation.
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● If the starvation state persists for more than 10 hours,
the cells switch to the selective form of autophagy,
namely Chaperon-mediated autophagy.
● The purpose of the CMA is to choose the best specific
protein to degrade since the cells need the best energy
source since the starvation is already beyond 10hours!!!