GENERAL PATHOLOGY AND CYTOLOGIC TECHNIQUES activated, and result in the loss of cell membrane integrity

and an uncontrolled release of products of cell death into the

extracellular
Father of Modern Pathology: Rudolf Ludwig Carl Virchow space.

4 Aspects of Pathology: This initiates in the surrounding tissue an inflammatory

1. Etiology: Origin of the Disease
2. Pathogenesis: Refers to the sequence of cellular,
biochemical and molecular events that follow the
exposure of cells or tissues to an injurious agent
3. Morphologic Changes: Refers to the structural
alterations in cells or tissues that are either characteristic
of a disease or diagnostic of etiologic process.
4. Functional derangements/Clinical manifestations: The
end result of genetic, biochemical and structural changes
in cells and tissues are functional abnormalities which
lead to the clinical manifestations of disease, as well as its
progress (Clinical course and outcome)
response which attracts leukocytes and nearby phagocytes
which eliminate the dead cells by phagocytosis. However,
microbial damaging substances released by leukocytes would
create collateral damage to surrounding tissues. This excess
collateral damage inhibits the healing process. Thus,
untreated necrosis results in a build-up of decomposing
dead tissue and cell debris at or near the site of the cell
death. A classic example is gangrene. For
this reason, it is often necessary to remove necrotic tissue
surgically, a procedure known
as debridement.

Stimulus

Adaptation biochemical level or structural changes

(microscopically visible)

Structural Changes

Physiological
Cellular Change
• within normal
pattern
• Ex. Enlargement
Thyroid gland
during pregnancy
Pathological
Cellular Change
• result to cell damage
• outside normal pattern
• failure to function
adequately Causes of Necrosis:
• caused by Harmful 1. Ischemia/Hypoxia
• Stimulus 2. Physical agents: Mechanical trauma, Extreme
temperature
3. Chemical agents: Strong acids and alkalis
4. Biologic Products: Endotoxins and Exotoxins

The type of necrosis is dependent on the nature, intensity and

duration of the
injurious agent, and the type of cell involved.

1. Coagulative necrosis –is characterized by the formation

• Example of Cellular adaptation: CHRONIC SMOKERS
➢ METAPLASIA: reversible
➢ Change of tracheal tissue (ciliated pseudostratified
columnar to stratified squamous tissue)
Why is Necrosis harmful?
Cellular death due to necrosis does not follow the apoptotic
signal transduction pathway, but rather various receptors are
of a gelatinous (gel-like) substance in dead tissues in
which the architecture of the tissue is maintained, and
can be observed by light microscopy. Coagulation occurs
as a result of protein denaturation, causing albumin to
transform into a firm and opaque state.
− Rapid coagulation of Cytoplasm due to
intracellular enzymes
− Ex. Myocardial infarction
2. Colliquative necrosis – Cells undergo lysis rapidly. in Nuclear Changes during Necrosis
contrast to coagulative necrosis, is characterized by the − There are also nuclear changes related to necrosis:
digestion of dead cells to form a viscous liquid mass
− fairly rapid total enzymatic dissolution of cells ➢ Margination of chromatin – chromatin condensing
with complete destruction of the entire cell. around the periphery of the nucleus
− Ex. Brain infarction ➢ Pyknosis – small and dense nuclei
3. Caseous necrosis – Mycobacterium tuberculosis interacts ➢ Karyolysis – complete lysis of the nuclei
with macrophages. The necrotic tissue appears as white ➢ Karyorrhexis – fragmented nuclei (generally seen in
and friable, like clumped cheese. apoptosis)
− The destroyed cells are converted into a granular,
friable mass made up of a mixture of coagulated
protein and fat.
4. Gangrenous necrosis – refers to the massive death of
tissue caused by combination of ischemia and
superimposed bacterial infection
− primary (bacterial toxins) or secondary (ischemia,
infection)
5. Fibrinoid necrosis – is a special form of necrosis usually
caused by immune-mediated vascular damage
− smooth muscle necrosis, fibrin release (malignant
hypertension)
Changes during Necrosis
6. Fat necrosis – is specialized necrosis of fat tissue, Irreversible cell injury is typically accompanied by:
resulting from the action of activated lipases on fatty
tissues such as the pancreas. Release of intracellular enzymes like:
− Adipose are split into fatty acids and glycerol  Cardiac muscle – creatine kinase (MB isoform),
without affecting the cell membrane aspartate transaminase, lactate dehydrogenase
 Hepatocytes – alanine transaminase
Types of Necrosis  Striated muscle – creatine kinase (MM isoform)
Coagulative Necrosis Liquefactive Necrosis Gangrenous Necrosis  Pancreas – amylase

Inflammation
− From the Latin word “inflammare” (to set afire)
− Universal response to tissue damage by wide range of
harmful stimuli including mechanical trauma, tissue
Fat Necrosis Fibrinoid Necrosis
necrosis and infection.

Purpose
➢ To destroy (or contain) the damaging agent
➢ To initiate repair processes
➢ To return the damaged tissue to useful function

Causes
Coagulative Necrosis – 1. Living organisms: ex. bacteria, viruses, fungi and
Adrenal Gland protozoa
2. Chemicals: ex. Turpentine.
3. Mechanical & Thermal injuries: ex. burns,
electricity and radiations.
4. Immune reaction: causes inflammation due to Ag-
Ab reaction. Ex. serum sickness
Changes during inflammation Eosinophils
− This cell is present in parasitic infection and
I - Blood vessels changes hypersensitivity
a. Momentary contraction of the Blood vessel
b. Vasodilation: causing more arterial blood i.e., Monocytes
hyperemia − It is phagocytes cells inside the blood & when reach
c. Increased permeability of venules & capillaries to the cells and tissue it will become macrophage
− the effect is leakage of Plasma proteins, RBCs & cells or called histiocytes
WBCs. − The function of macrophage is phagocytosis of the
foreign body
II - Changes in blood stream − Removes (scavengers) the debris
a. Changes in Erythrocyte distribution − They fuse to form multinucleated giant cells (Ex.
b. Leukocytes margination (pavementing) Langhan's giant cell.)
Its mechanisms either:
a. WBCs gets adhesive Epithelioid cells
b. Capillary wall gets sticky (endothelium gets − It’s similar to macrophage and similar o epithelial
sticky) cells close to each other with no different borders
between its cytoplasm & they tend to have small
III - Changes in rate of flow nucleus
a. Acceleration of the rate: due to arteriolar dilation − These cells are no phagocytic cells but release
lysosomal enzyme.
IV - Leukocytic emigration
− Ameboid movement. Giant cells
− Cause: chemotactic forces Form by fused the cytoplasm of the macrophages (2 – 3 or
reach to 20). There are 4 types of
Chemotaxis: process of attraction of leukocytes to certain giant cells.
area that has the chemotactic substances (ex.: C5a)
1. Langhan's giant cell
Chemotactic substances are: -Wherein their nuclei can be located at the periphery
1. Products from pathogenic bacteria. 2. Foreign body giant cells
2. Substances from injured-cells. ex. mechanical or 3. Touton Giant cell
thermal injuries 4. Warthin-Finkeldy
3. Certain chemicals ex. turpentine.
4. Serum complements ex. C3 (anaphylatoxin)

V - Diapedesis of WBCs
− It is the movement of the WBC from the blood vessel Classification of the inflammation
to the site of inflammation
According to:
VI - Serum exudation: 1. Time
Function of the exudate 2. Type of exudate
1. It greatly dilutes toxic substances formed within the 3. Organ
body especially bee-stings & snake-bite.
2. It has blood serum that brings with its antibodies i.e., 1. Time
it brings humoral immunity against specific a. Acute Inflammation: extend from hours to few days
infections.  Infiltration of P.M.N.C.
3. Brings leukocytes to the area for phagocytosis.  Edema
4. Fibrinogen in the exudate forms fibrin. Fibrin may
support ameboid movement of leukocytes. b. Subacute Inflammation: extended from days to
5. Has mechanical action by washing the irritant. weeks -->presence of macrophages & lymphocytes

Neutrophils c. Chronic Inflammation: extended from weeks,

− The action of neutrophils is phagocytic months, years --> mononuclear cells (macrophages
− Phagocytic power is shown toward bacteria and giant cells)
− It will produce pus & this process call suppuration or
purulent exudate
CLASSIFICATION OF INFLAMMATION
Acute Inflammation
➢ sudden onset
➢ vascular dilatation
➢ increased vascular
permeability
➢ neutrophil activation and
migration
➢ predominantly PMNs
(Hallmark)
➢ Polymorphonuclear cells
ex: Neutrophil
➢ when this fails to subside
within several weeks à
chronic inflammation
3 – Purulent Inflammation
Chronic Inflammation − It is the inflammation characterized by pus
➢ lasts for weeks or formation
months/years − PUS is a liquid of creamy color & consistency but
can be thin (watery) or (semi-solid). The color is blue
➢ predominantly green when caused by Pseudomonas aeruginosa.
mononuclear
(macrophages,
lymphocytes, plasma
a. Suppurative inflammation: implies that large
cells) but PMNs may amounts of pus is produced.
➢ also be present b. Phlegmonous inflammation: is inflammation when
there is good amount of pus diffusely scattered
through a tissue especially the subcutis.
c. Abscess: is a circumscribed collection of pus with a
capsule of Connective Tissue

2. Type of Exudate Microscopic Appearance:

1 – Serous inflammation (serous exudate)
− It is characterized by increase exudation of the clear
albuminous fluid which accumulates in the
inflammation area showing the inflammatory edema
Microscopic App:
1. Watery fluid is seen in the cavity
2. Cloudy fluid & it has fibrin strands
3. Color could be red if there are RBC present
Causes:
1. Mechanical injury of tissue.
2. Chemical → chloroform.
3. Biological --> virus
4. Insects --> bee sting
2 – Fibrinous inflammation
− Characterized by too much fibrinogen clotting fibrin
and precipitation of fibrin masses
− Acute inflammatory exudates with a high plasma
protein content
Occurrence:
1. Mucus membrane (digestive & respiratory
system)
2. Serous surface.
3. Lungs and joints.
Microscopic app:
1. Fibrin is present in network
2. Precipitated protein + WBC + RBC
3. There is hyperemia
Macroscopic app:
1. The organs are firmer and tenser (ex. lungs)
because present of fibrin.
2. Fibrin appearance: string white or yellowish
netlike material
1. Large number of degenerate neutrophils are seen.
Can be caused by the ff. Bacteria:
Pyogenic Bacteria
1. Staphylococci
2. Streptococci (S. pyogenes, S. pneumoniae)
3. E. coli
4. Neisseria (meningococci & gonococci)
4 – Hemorrhagic Inflammation
− Characterized by large numbers or RBC's that leave
by diapedesis. The blood may exudes from body
surface or nearby tissue.
Occurrence
1. Septicemic diseases ex. Anthrax, Pasturellosis.
2. Hemorrhagic gastritis & enteritis.
3. Lungs.
Microscopic Appearance:
a. Free RBC
b. Serum, fibrin and leukocytes
Gross APP:
1. See blood-colored fluid or semi fluid usually
clotted & gelatinous.
2. Streaked: vary in color &. consistency
3. Deep red inflamed surface
4. In hemorrhagic enteritis, feces colored black
(except when hemorrhagic inflammation is
present in the last part of intestine),
5. In lungs: blood is foamy.
Other possible causes:
1. Organisms of high virulence ex. Leptospira.
2. Poisonous chemicals ex. Phenol, Arsenic,
Phosphorus.
5 – Catarrhal Inflammation CHRONIC INFLAMMATION
− Is inflammation in which the exudate is mucus
− The latter comes from the epithelial cells of mucous Subdivisions:
glands or from the goblet cells. 1. Non-specific chronic inflammation
arises following non-resolution of acute inflammation
− Inflammation of the mucous membranes 2. Specific (Primary) chronic inflammation
− It can result in a thick exudate of mucus and white arises de novo in response to certain types of injurious
blood cells agents
− caused by the swelling of the mucous membranes in 3. Granulomatous inflammation
the head in response to an infection. subset of specific inflammation characterized by the
Can be seen in: presence of granulomas
− middle ear − sinus
− adenoids − tonsil
OUTCOME OF NON-SPECIFIC CHRONIC
− chesty cough −
INFLAMMATION
− common colds
Factors which impair healing:
• The first 4 cardinal signs were first described by Aulus 1. Poor nutrition
Cornelius Celsus. The 5th cardinal sign was included 2. Immunosuppression
by RC Virchow. 3. Persistent tissue damage infection
4. Retained foreign material
• Rubor – “redness” 5. Sequestered dead tissue
− due to arteriolar and capillary dilatation with 6. Poor blood supply
increased rate of blood flow towards the site of injury
Factors which aid the healing of Chronic inflammation:
• Tumor – “swelling”
1. Administration of appropriate antibiotics
− due to increased capillary permeability causing
2. Surgical removal of foreign material
extravasations of blood fluid
3. Surgical removal of sequestered dead tissue
• Calor – “heat”
4. General attempts to improve nutrition
− due to transfer of internal heat to the surface or site of
injury, brought about by increased blood content SPECIFIC (PRIMARY)CHRONIC INFLAMMATION
(hyperaemia)
• Dolor – “pain” Types of agents:
− due to pressure upon the sensory nerve by the Immunological
exudates/tumor 1. Low toxicity organism as Treponema
− (resulting from release of bradykinin and PGE2) 2. Infective organisms that grow within the cell
➢ Functio laesa – “diminished function” 3. Hypersensitivity reactions
− destruction of the functioning units of the tissue 4. Autoimmune conditions (SLE)
5. Infection by fungi and parasites
What is suffix used to denote inflammation?
A. -Carcinoma Non-immunological
B. -oma 1. Foreign body reaction
C. -itis 2. Inert noxious materials (silica, asbestos)
D. -ase
GRANULOMATOUS INFLAMMATION
− presence of activated macrophages (Often with added
T-Cells) and multinucleate giant cells

Inflammation of: Examples:

Appendix ➢ Appendicitis 1. Mycobacterium tuberculosis –Caseating granuloma
Fallopian Tube ➢ Salpingitis 2. Leprosy (Mycobacterium leprae) – Non-caseating
Pericardium ➢ Pericarditis granulomas
Pleura ➢ Pleurisy 3. Syphilis (Treponema Spp.) – Gummas
Subcutaneous tissues ➢ Cellulitis 4. Cat Scratch Disease – Rounded or Stellate
Meninges ➢ Meningitis Granuloma
Arteries ➢ Arteritis 5. Sarcoidosis- Non-caseating granulomas with
abundant activated macrophages
 4. Atresia – failure of an organ to form an opening
Example: Imperforateanus and Biliary Atresia

B. Atrophy – decrease in size of a normally mature

Changes in cellular growth patterns
1. Change in the size of the cells
2. Change in the differentiation of cells
3. Change in the rate of cell division
Retrogressive Changes (organ/tissues smaller than normal)
tissue/organ resulting from the reduction in cell size or
decrease in the total number of cells
 Physiologic – occurs as a natural consequence of
maturation
Examples: Atrophy of thymus during puberty
Atrophy of brain and sexual organ (at about 50 years old)

A. Developmental defects  Pathologic – as a consequence of disease

▪ Aplasia Examples:
▪ Agenesia Endocrine Atrophy
▪ Hypoplasia Atrophy of disuse
▪ Atresia Starvation/Hunger Atrophy
Pressure Atrophy
1. Aplasia – incomplete/defective development of a Vascular Atrophy
tissue/organ most commonly seen in one paired
structures (kidneys, gonads) represented only by a mass
of fatty/fibrous tissue
-NO RESEMBLANCE TO ADULT STRUCTURE

Progressive changes (Increased Cell Mass) – organ/tissues

2. Agenesia – non-appearance of an organ larger than normal
➢ Hypertrophy – increase in the size of existing cells (ex.
exercise)

1. True Hypertrophy- due to increased workload or

3. Hypoplasia – failure of an organ to reach its full, mature
size.
increase in endocrine stimulation
2. False Hypertrophy- due to edema or connective
tissue proliferation
3. Compensatory Hypertrophy- Involved in Paired
organs when the other organ is removed
− One organ compensates for the entire workload
➢ Hyperplasia – increase in cell number as a consequence
of cell division (Cushing syndrome)
2 categories: Physiologic and Pathologic

Testes in Klinefelter's Thymus in

Syndrome DiGeorge syndrome
Degenerative changes – tissues have abnormalities Bone Liver Cells Liver Cell Hepatocarcinoma
Adenoma (Hepatoma)
✓ Anaplasia (dedifferentiation) – usually used as a criterion Neuroectoderm Nevus/Mole Melanoma
toward malignancy (melanocarcinoma)
✓ Metaplasia – reversible change involving transformation Kidney Renal Adenoma Renal
in one type of adult cell to another adenocarcinoma
✓ Dysplasia – (Atypical hyperplasia). This generally
consists of an expansion of immature cells, with a Grading of Tumors
corresponding decrease in the number and location of “Grading” – grading of cancer attempts to establish some
mature cells. Dysplasia is often indicative of an early estimate of its aggressiveness or level of malignancy based
neoplastic process on:
✓ Neoplasia (Tumor) – continuous abnormal proliferation 1. the cytologic differentiation of the tumor
of cells without control (no purpose or function) 2. the degree of variability of cellular shape and size
(pleomorphism)
tumor cells
3. the number of mitosis within
Note: Well- differentiated tumors as a rule are less
malignant than undifferentiated tumors.

Broder’s Classification
NEOPLASM Differentiated Undifferentiated
− is an abnormal mass of tissue as a result of neoplasia. GRADE I 100% to 75% 0 to 25%
 Neoplasia "new growth" is the abnormal proliferation of GRADE II 75% to 50% 25% to 50%
cells GRADE III 50% to 25% 50% to 75%
GRADE IV 25% to 0 75% to 100%
Nomenclature of Neoplastic Cells:
Staging of Tumors/Cancers
*Benign neoplasms “Staging” – is based on:
− Grow slowly and remain localized to the site of origin ➢ The size of the primary lesion
− suffix: -oma ➢ Extent of spread to regional lymph nodes
*Malignant neoplasms ➢ Presence or absence of metastases
− are collectively referred to as cancers
TNM System of Cancer Staging
− grow rapidly and may spread widely
− applicable to all forms of neoplasia
− Suffix: -Sarcoma (mesenchymal/connective tissue)
T – for primary tumor
→ Carcinoma (epithelial tissues)
T1, T2, T3, T4 – with increasing size of the primary
lesion
Mesenchymal/Connective Tissue Tumors
N – for regional lymph node involvement
BENIGN MALIGNANT
N0, N1, N2, N3 – indicates progressively advancing
Fribrous tissue Fibroma Fibrosarcoma
nodal disease
Adipost tissue Lipoma Liposarcoma
M – for metastases
Cartilage Chondroma Chondrosarcoma
M0 or M1 – whether there are distant metastases
Bone Osteoma Osteocarsoma
Blood vessel Hemagiona Hemagiosarcoma
Smooth muscle Leimyoma Leiomyosarcoma T0 = breast free of tumors
Striated muscle Rhabdomyona Rhabdomyosarcoma T1 = local lesion <2 cm in size
T2 = lesion 2-5 cm in diameter
Hematopoietic cells Leukemia T3 = lesion >5cm in diameter
Lymphoid tissue Lymphoma T4 = skin and/or chest wall involved

Epithelial Tissue Tumors NO = no axillary nodes involved

BENIGN MALIGNANT N1 = mobile nodes involved
Strat. Squamous Sq. cell papilloma Sq. cell carninoma N2 = fixed nodes involved
Glands and Adenoma Adenocarcinoma N3 = ipsilateral internal mammary node involved
Ducts
Renal Renal Tubular Renal Cell MO = no metastases
Epithelium Edenoma Carcinoma M1 = demonstrable metastases
MX = suspected metastases