Pathology - it is an area of science focusing in all the changes of
cells, tissues and organs that underlie a disease. It is the study of 1) Atrophy acquired decrease in tissue or organ size
diseases. a) Physiologic occurs as a consequence of maturation
I. atrophy of thymus during puberty and atrophy of brain
and sex organs
Etiology - refers to the cause, it could be genetic or II. Decrease in breast and uterus size after child birth
acquired b) Pathologic the decrease in tissue or organ size is due
Pathogenesis - the manner in how the disease had to a disease
developed, refers to sequence of events i. Vascular Atrophy may happen because of
Molecular and Morphologic Changes - in every diseases sudden cut off of blood supply
process, initially affected is the cell, next tissue, then later ii. Starvation/Hunger Atrophy may happen due to
organs. Refers to the changes in cells, in tissues that could lack of nutritional supply
be structural, biochemical, or morphological. iii. Exhaustion Atrophy may develop due to
Functional Derangement & Clinical Manifestations - excessive workload
even the normal functioning of the organ will be affected iv. Endocrine Atrophy may happen because of
and as a result the patient will show manifestation of lack of hormones needed to maintain normal size
disease. v. Atrophy of Disuse due to inactivity or
diminished function
vi. Pressure Atrophy continuous pressure may
Aplasia - the incomplete or defective development of tissue cause direct injury to the cell causing it to
or organs. The affected organs shows no resemblance to become smaller
the normal adult structure. Usually common in paired
structure like kidney and gonads. 2) Hypertrophy increase in tissue or organ size due to an
Agenesia - refers to the complete non appearance of an increase in the size of individual cells comprising an organ.
organs, absence of organs No new cells are produced.
Hypoplasia - the failure of an organ to reach its normal i. Physiologic hypertrophy - normal I.e. hypertrophy of
mature skeletal muscles - increase in skeletal muscle size
Atresia = Biliary atresia - the bile duct between the liver and following exercise
small intestine is either blocked or absent (may happen in ii. Compensatory hypertrophy - may happen if one of the
newborns); imperforate anus; microtia - absence of ear paired organ is removed I.e. Renal hypertrophy
canal; refers to the failure of an organ to form an opening; a iii. Pathologic hypertrophy - due to a disease I.e
condition in which an orifices or a passage in the passage is Hypertrophy of Myocardium (muscle layer of the heart)
either close or absent. due to aortic valve disease or hypertension
All normal cells may be exposed to a lot of injurious stimuli 3) Hyperplasia increase in tissue or organ size due to an
or stressful stimuli. increase in the number of cells making up the organ. No
Reversible injury - the affected cell can get back to its cells are added. New cells are produced.
normal conditions by using several adaptive cellular i. Physiologic - normal I.e. Increase in breast size during
mechanism puberty=Hyperplasia of the breast during puberty,
Irreversible injury - the affected cell can no longer get back Increase in uterus and breast size during pregnancy,
to its normal state; the point of no return; lead to cell death Erythroid Bone Marrow Hyperplasia (may develop in
Apoptosis and Necrosis is a pattern of cell death individuals living in high altitude
ii. Pathologic - due to disease; may give rise to neoplasm;
may br due to stimulation of growth factors
INJURIOUS Examples of Pathologic Hyperplasia
STIMULI INJURY Hyperplasia of pancreatic islets in infants of a
or NORMA diabetic mother (stimulated by high glucose level)
L CELLS a) Reversible
STRESSFUL b) Irreversible Lymphoid tissue hyperplasia occurring after
STIMULI localized inflammation
Increase in the number of lymph nodules (TB of
Adapted cervical lymph nodes)
REVERSIBLE “Cellular cells Hyperplasia of endometrium due to excessive
INJURY adaptations” NORMAL estrogen (excess hormonal stimulation)
CELLS Diffuse crowding of epithelial cells forming
papillary projections (Grave’s Disease)
“APOPTOSIS
4) Metaplasia a reversible process; involves the
IRREVERSIBLE (PHYSIOLOGIC) DEAD transformation of adult cell into another adult cell
INJURY NECROSIS CELLS Epithelial metaplasia cell involved is epithelial cell
(PATHOLOGIC)
”
Mesenchymal metaplasia cell involved is connective
cells
5) Dysplasia / Pre-neoplastic Lesion or Atypical Metaplasia Rubor refers to redness due to increase dilatation of blood
Abnormal growth and differentiation; variation of size, vessels causing an increase in the rate of blood flow
shape and orientation; a pre-neoplastic lesion (a stage Dolor is pain due to the release of chemical subs. Like
in the cellular evolution to cancer); may lead to cancer bradykanin causing stimulation of nerve endings for pain
but not necessarily Calor is heat due to the transfer of internal heat to the
A reversible process; no cell transformation surface or to the site of injury
Cervical intraepithelial neoplasia Tumor is swelling may happen due to extravascular
accumulation of fluid
6) Anaplasia / De-Differentiation Functio laesa due to the destruction of functioning units of
An irreversible process; characterized by transformation the tissue
of adult cell to primitive or embryonic cell type
Often use as a criterion for malignancy
7) Neoplasia the process of tumor formation; characterize by
the continuous proliferation of abnormal cells (no function); Somatic Death refers to the death of the entire body.
Neoplasm - refers to new growth commonly known as Primary changes are changes that can be noted
tumor immediately after death
Cancer - the common term for all the malignant tumors Secondary changes that can be noted few hours after
Oncology - study of tumors or neoplasm death
1. Algor Mortis
Apoptosis refers to program cell death; a physiologic refers to the cooling of the body
phenomenon; the affected cell become smaller; the plasma the first secondary change to appear
membrane remains intact and the cellular contents do not leak important in establishing time of death
out; no inflammation; characterize by cell shrinkage happens in 7 degree F
Necrosis happens when the cells DNA and proteins are damage faster in cold weather and malnourished individual
beyond repair and the cells kill itself by apoptosis and become Usually delayed if the cause of death is infection
smaller; it is accidental and unregulated its pathologic cell death; 2. Livor Mortis / Lividity / Post mortem hemolysis
there is cell swelling (the affected cell is usually enlarged); the Refers to the purplish discoloration of the skin due to
plasma is disrupted therefore cellular contents leak out; there is sinking of fluid blood into capillaries of the dependent
inflammation parts of the body
Coagulative necrosis - due to sudden cut off of blood 3. Rigor Mortis
supply; usually happens in solid organs like the heart, Also called rigidity
kidney and adrenal glands not in the brain; the Refers to the stiffening of muscles
affected organs on gross examination appear like It occurs 6-12 hours after death
boiled material Persist for 3-4 days
Liquefactive necrosis - due to complete digestion of 4. Post mortem clotting
dead cells; characterize by softening of necrotic The blood inside the body clotting
material due to the action of hydrolytic enzymes; the 5. Dessication
affected organs appear liquidy and creamy yellow Refers to the drying and wrinkling of the anterior
because of pus chamber of the eye and cornea
Caseous necrosis - a combination of coagulative and 6. Putrefaction
liquifactive necrosis; the affected organs appear soft Release of foul odor due to increase in saprophytic
and greasy resembling cabbage cheese; usually seen organ, manifested by greenish discoloration of
in Tuberculosis abdomen due to invasion of microorganism
Fibrinoid necrosis - due to immune reaction in the 7. Autolysis
blood vessels; the changes is too small to see grossly;
in microscopically the affected blood vessels appears
thickened The microscopic examination of cells taken from
Fat necrosis - seen in acute pancreatitis; the necrotic different body sites for diagnostic purposes. May also be carried
material or the affected organs appear chalky white out malignant or cancerous condition. The advantages of
precipitates diagnostic cytology are:
Gangrenous necrosis - is not a specific pattern of cell It is cause effective
death; usually apply to a limb generally to a lower leg The procedure is simple because following collection of
that lost its blood supply cells is we prepare smear then evaluate the cells
Wet gangrene due to venous occlusion It has low complication rate since collection of specimen
Dry gangrene due to arterial occlusion does not require surgical procedure.
It has high diagnostic accuracy.
COMMON FIXATIVES for CYTOLOGIC SMEARS
Equal parts of 95% ethyl alcohol & ether (the best but not
commonly used because it is volatile and flammable)
This involves the examination of cells specifically the 95% ethyl alcohol - the most commonly used fixative in
disquamated cells or shed cells from epithelial surfaces. cytology ( tissue fixative 10% formalin)
Specimen can be classified into two categories: Carnoy’s fluid -- for blood specimen
Gynecological - cervicovaginal smear (PAP smear) Spraycyte or cytospray - polyethylene gycol and isoprophyl
Non-gynecological - sputum, urine, csf, peritoneal and alcohol must be keep a distant of q foot in the slide
pleural fluid Equal parts of tertiary butyl alcohol and 1 part 95% ethanol
Schaudinn’s fluid
Processing of specimen except PAP smear Saccomano preservative - 50% ethyl alcohol and 20%
Centrifugation carbo wax
Get the sediment and used for smear preparation
The excess sediments is used for cell blocked technique
Screening test for cervical cancer
Preparation of Smear Uses:
Smears are ususally made from fresh material Determination of etiology of certain infections
See requisition form (patients ID, name, age, date and type Determination of ovarian function
of specimen) One test to assess infertility
Label the slide Evaluation of response of malignancy to post radiation or
Methods of smear preparation chemotherapy
There are four ways to prepare smear: streaking, spreading, Barr body determination
pull-apart, touch or impression smear (abraded cytology) Medico legal examination of sexual assault
There are specimens with increase protein will no longer require Pap Stain - it is consist of 3 stains, developed by George
addition of adhesive. However with low protein content require Papanicolau, the father of cytopathology
addition of adhesive. 1) Harris Hematoxylin it stained the nucleus; nuclear stain,
the primary dye
Specimens the REQUIRE the addition of ADHESIVE 2) OG6 the first counter stain; this will stain the cytoplasm of
1) Concentrated sputum mature superfacial cells
2) Urinary sediments Orange green 6, 0.5 solution in 95% alcohol &
3) Bronchoalveolar Lavage (BAL) phosphotungstic acid
4) Enzymatic Lavage from GIT 3) EA50 the second counter stain; this will stain the cytoplasm
of immature cells such as intermediate and para basal cells
Adhesives A polychrome mixture of Eosin Y, light green SF and
APES Bismarck brown Light greeen SF, yellowish 0.1%
Leuconostoc Culture solution in 95% alcohol, Bismarck brown 0.5 in 95%
Celloidin ether alcohol alcohol, Eosin Y 0.5% in 95% alcohol Phosphotungstic
Cold serum or plasma acid, lithium carbonate
Note: EA 50 is comparable to EA 36
Note: Procedure
**The routine tissue adhesive is Mayer’s Egg Albumin. The 1. Fixation with 95% ethanol - lead to degeneration of cells
routine adhesive in cytology never used the mayers egg albumin. 2. Hematoxylin
**Adhesives must be permeable to both fixative and stain; must 3. Differentiate with acid alcohol then wash with water
not retain the stain 4. Ammonia water then wash
5. OG6
Why not Meyers Egg Albumin? 6. 95% ethanol - washing, 2 changes
Because is intensely stain by the counter stain in PAP smear. It 7. EA 50 or 36
will take up the color or dye. 8. Dehydration
9. Xylol
10. Mount and label
If the specimen is pap smear, the first step is the fixation. Results
Smears must be prepared and immediately immerse in Nucleus Vesicular nucleus = blue
fixative while still moist & before drying occurs Pyknotic nucleus = dark blue to black
FIX ASAP since exfoliated cells decomposed rapidly which Cytoplasm OG6 = orange with a hint of green
may destroy cellular and nuclear details, in turn will give EA 36 to 50 = olive green with a hint of
inadequate results for diagnosis brown and red
Centrifuge at 2000 rpm for 2 minutes, supernatant must be Bacteria Dark blue
decanted, use sediment for smear preparation
Mycelia violet
Extra sediment - CELL BLOCK TECHNIQUE
T. vaginalis Pale greenish blue
4) Basal Cells
It do not shed naturally, it is shed traumatically
Small (13-20u) round, slightly oval cells, with relatively
1) Superficial Cells large nucleus occupying half or more of the cell
Most mature, large 30-69u volume
Polyhedral flat cells with small dark pyknotic nuclei (less Cytoplasm is strongly
than 6u) basophilic
Cells that shows TRUE ACIDOPHILIA (the Found only in vaginal
characteristics of vaginal cells under the influence of smears only before
estrogen), cytoplasm may be acidophilic or basophilic pregnancy and after
menopause
A) Class System - no longer used, last used December 1988);
obsolete
2) Intermediate Cells Class I - Negative for malignant cells
Medium size cells;a polyhedral cells Class II - atypical cells present, but negative for malignant
Cytoplasm: basophilic with vacuoles, vesicular nuclei (6- cells
9u) Class III - suspicious for malignant cells
Class IV - strongly suggestive for malignant cells
Class V - conclusive for malignant cells
B) Bethesda System - developed at national cancer institute in
December 1988;
Report Format:
Specimen adequacy
General categorization
2.1 Navicular Cells
Descriptive diagnosis
Boat shaped cells with a tendency to fold or curl on
edges
Found in the latter half of menstrual cycle, menopause
and during pregnancy
Presence suggest progesterone-estrogen stimulation,
either endogenous or exogenous
2.2 Pregnancy Cells
Round to oval shaped cells with
translucent basophilic
cytoplasm due to glycogen
accumulation
Nucleus pushed @ periphery
with double walled boundary
appearance
Cytoplasm stains deep blue or
blue green + cell membrane
3) Parabasal Cells
Smaller than intermediate cells
Fried egg appearance
Thick round to oval cells (15-25u), with strong basophilic
cytoplasm and vesicular nuclei (6-9u)
Normally found in increase number following child birth
after childbirth after abortion, menopause and two
weeks of age to puberty