3. Special pathology which deals with the application of the basic changes learned in general pathology
to the various specific diseases eg Diabetes, atherosclerosis etc.
4. Diagnostic Pathology (Histopathology) which deals with the study of tissue abnormalities using gross
and microscopic examination of biopsy samples.
Biopsy: The biopsy is a tissue sample obtained surgically from a living body in order to be examined
grossly and microscopically (by a pathologist) to help in establishing the diagnosis.
5. Cytopathology which deals with the study of cellular changes. Exfoliative Cytology / FNAB
6. Surgical Pathology which refers to histopathological examination of biopsy samples surgically
removed from living bodies. (Realted to #4)
7. Post-mortem pathology which deals with pathological examination of an animal or human cadaver
(carcass) after death. It is also known as autopsy or necropsy.
8. Forensic pathology: It is the subspecialty of pathology that focuses on the medico-legal investigation
of the cause of a sudden or unexpected death by examination of a dead body. The term forensics is
derived from the Latin word forensis which means forum (law court).
9. Physiological pathology which deals with the study of alterations in the functions of organs and
systems of the body as a result to a disease. It is also known as pathophysiology; e.g., pathophysiology
of indigestion, diarrhea, abortion…..etc.
10. Immunopathology which deals with the study of diseases mediated by immune reactions. Such as
immunodeficiency diseases, autoimmune diseases and hypersensitivity reactions.
11. Molecular pathology which deals with the study of alterations that take place at the molecular level
(e.g., DNA damage) as a result to a disease.
12. Experimental pathology: It is the study of diseases that have been created or induced experimentally
to analyze the structural & functional abnormalities in tissue to better understand the mechanism of
underline diseases. Usually laboratory animals used in experimental pathology (Rabbits Rats, Mice….ect.
4 Aspects of the Disease Process
The four aspects of a disease process that form the core of pathology are:
1. Its cause etiology)
2. The mechanisms of its development (pathogenesis)
3. The biochemical and structural alterations induced in the cells and organs of the body
(molecular and Morphologic changes)
4. The functional consequences of these changes (clinical manifestations).
ETIOLOGY



Also known as the “Cause”
The concept that certain abnormal symptoms or diseases are Caused is as ancient as recorded
history.
For the Arcadians (2500 BC), if someone became ill it was the patient’s own fault (for having
sinned) or the effects of outside
Agents, such as bad smells, cold, evil spirits, or gods.
There are two major classes of etiologic factors: a-genetic (e.g, inherited mutations,
Disease-associated, gene variants, or polymorphisms) bacquired (e.g., infectious, nutritional, chemical,
Physical).
Pathogenesis
MOLECULAR &
MORPHOLOGIC CHANGES refer to the structural alterations in cells or tissues that are either
characteristic of a disease or diagnostic of an
Etiologic process
Determine the nature of a disease and follows its progression.
Example: pneumonia -> inhalation -> mucosa – Blood vessel – lungs – causes edema – them forms
phlegm causes difficulty of plegm
Disease
Disease is a Pathophysiological response to external or internal factors
Example:
Cardiovascular disease is a class of diseases that involve the heart or blood vessels that includes
coronary artery disease AD) such as angina and myocardial infarction
Disorder
Disorder is the disruption to regular Bodily structure and function
Example: Disorder Resulting from Cardiovascular disease Is an arrythmia or heart failure. Disorder Can
be Mental, Physical, Genetic Emptional, Behavioural and Structural
Syndrome
Syndrome refers to a disease or a disorder
That has more than one identifying feature or
Symptom. It is aCollection of signs and symptoms associated with a specific health- related cause
Example: Down syndrome is a well-Having an extra copy of Known genetic disorder, and is characterized
by cal, chromosome 21 in combination with a number of distinctive physical features at birth.
Condition
Symptom-refers to any evidence of a disease as told by the patient (in case of human being).
Sign refers to any evidence of a disease detectable to a clinician (can be observed by the clinician).
Diagnosis:
The term diagnosis refers to the art or act of identifying a particular disease from its signs and
symptoms.
Determination of the nature of a disease expressed in concise manner
Prognosis prediction of the probable outcome of a disease in a living individual.
O It is the clinicians estimate of the severity and possible result of a disease
O A forecast of the probable course and outcome of a disease, especially of the chances of recovery
A Diagnosis is an identification of a disease via examination.
The prefix dia- can mean “through,” “during.” Or “across,” so diagnosis can be thought of as a
recognition of a disease during examination or observation.
Acute diseases
1. The diseases that develop quickly and last for a short period of time are called acute diseases.
Short
2. These diseases do not have long term adverse effects on the health of an individual. –
3. These diseases are not fatal.
4. Example: Common cold, malaria, etc.
Chronic diseases
1. The diseases that last for a long period of time sometimes even for a lifetime are called chronic
diseases.
2. These diseases often have long term effects on the health of an individual.
3. These diseases are fatal.
4. Example: Cancer, HIV, etc.
Idiopathic- a disease with no identifiable cause
- A diagnosis of exclusion.
- There is limited literature describing the methodology to define a disease with no clear
diagnostic criteria.
- Cause is unknown
Iatrogenic-pathology caused by a physician and their treatment.
Ex. Retained forceps after abdominal surgery causing intestinal obstruction.
Community acquired infection- infection acquired outside a health care facility.
Nosocomial infection- hospital acquired infection.
- Occurs within 48 hours of hospital admission , 3 days of discharge or 30 days of
operation.
Non communicable diseases \(NCD)- Diseases that are not transmitted through contact with an infected
or afflicted person.
- They are caused by various genetic, physiological, environmental, and behavioral
factors.
4 main types of NCD’s (WHO)
1. Cancer
2. Cardiovascular diseases
3. Chronic Respiratory diseases (Asthma and COPD)
4. Diabetes
Communicable diseases- Diseases that can be spread from one organism to another. This includes
spread from one person to person or animal to humans (zoonotic).
COMMUNICABLE DISEASES:
The manner of spread can be described by 2 terms
1. Infectious-act affect or contaminate someone with pathogenic microorganisms.
Major ways of spread:
1. Infectious-act with an infected person, animal or their discharges (saliva; body fluids such as
blood, urine, semen; respiratory droplets/ aerosols)
2. Direct contact with contaminated object
3. Contaminated food or water
4. Disease carrying insects (Vectors)
2. Contagious- spread through direct bodily contact with an infected person, their discharges or an
object or surface they have contaminated.
From Latin ‘contagio’ - touching, contact.
All communicable diseases are infectious but not all are contagious. An infectious disease is contagious
when it spreads through direct, bodily contact with an infected person, their discharges, or an object or
surface they have contaminated.
ALL COMMUNICABLE DISEASES ARE INFECTIOUS BUT NOT ALL ARE CONTAGIOUS.
OUTCOMES OF DISEASE
There are four possible outcomes of disease:
1. Healing and recovery
2. Functional insufficiency (Functional shortage)
3. Death
4. Impasse: (carrier state)
An impasse is that steady (stable) state where the pathological. Agent cannot induce sufficient damage
to cause functional impairment or death, at the same time the body cannot eliminate that pathological
agent (No complete healing).
An example of impasse Is the carrier states in human where a disease is present in a subclinical manner
(i.e., no observable Signs and symptoms of the disease are present) such as the carrier States of
salmonellosis in human.
RUDOLPH VIRCHOW – FATHER OF MODERN PATHOLOGY
Cellular Responses to Stress & Noxious Stimuli
⚫Homeostasis – steady state
Adaptations reversible functional and structural responses to more severe physiologic stresses and
some pathologic stimuli, during which new but altered steady states are achieved, allowing the cell to
survive and continue to function
ADAPTATIONS (Adaptive responses)
1. Hypertrophy: refers to an increase in the size of cells. Resulting in an increase in the size of the
organ.
2. Hyperplasia: Hyperplasia is an increase in the number of Cells in an organ or tissue, usually
resulting in increased mass of the organ or tissue.
3. Atrophy: reduced size of an organ or tissue resulting from a Decrease in cell size and number.
Atrophy can be physiologic or pathologic often resulting to decrease in size and metabolic
activity of cells.
4. Metaplasia :Metaplasia is a reversible change in which one differentiated cell type (epithelial or
mesenchymal) is replaced by another cell type
HYPERTROPHY
⚫Hypertrophy can be physiologic or pathologic.
1. Physiologic Hypertrophy:
Examples:
- Increase in muscle due to “body building”
- Increase in the size of the uterus during pregnancy
2. Pathologic Hypertrophy (due to disease): Increase in the size of the ventricles due to usually
chronic hemodynamic overload, resulting from either hypertension or faulty valves.
HYPERPLASIA
HYPERPLASIA
Physiologic hyperplasia can be divided into:
1. (hormonal hyperplasia, which increases the functional capacity of a Tissue when needed, and
2. compensatory hyperplasia, which increases tissue mass after Damage or partial resection.
Hormonal hyperplasia is well illustrated by the proliferation of the glandular epithelium of the female
breast at puberty and during pregnancy, usually accompanied by enlargement (hypertrophy) of the
glandular epithelial cells.
Compensatory hyperlasia – based on greek mythology
Pathologic Hyperplasia
Most forms of pathologic hyperplasia are caused by excesses of hormones or growth factors acting on
target cells.
Endometrial hyperplasia is an example of abnormal hormone-induced hyperplasia
Atrophy reduced size of an organ or tissue resulting from a decrease in cell size and number. Atrophy
can be physiologic or pathologic Often resulting to decrease in size and metabolic activity of cells.
ATROPHY
•DECREASED WORKLOAD
• DENERVATION
• DECREASED BLOOD FLOW
• DECREASED NUTRITION
(2-4 are pathologic)
• AGING (involution)
• PRESSURE
METAPLASIA
A SUBSTITUTION of one NORMAL CELL or TISSUE type, for ANOTHER
-COLUMNAR SQUAMOUS (Cervix)
-SQUAMOUS→ COLUMNAR (Glandular) (Stomach)
-FIBROUS→ BONE
Example: smoking
- Metaplasia can cause Cancer
- Lead to inflammation
Inflammation
During repair, the injured tissue is replaced by:
◆Regeneration of native parenchyma cells
◆Filling of the defect by fibroblastic tissue or both
Inflammation and repair are protective response, however they may induce harn e.g.anaphylactic
reaction, rheumatoid arthritis, atherosclerosis or pericarditis.
The Inflammatory response consists of two main components:
1. A vascular reaction 2. A cellular reaction.
Tissues and cells involved in inflammatory response:
The fluid and proteins of plasma, circulating cells, blood vessels and connective tissue
 The circulating cells: neutrophils, monocytes, eosinophils, lymphocytes, basophils, and platelets.
 The connective tissue cells are the mast cells, the connective tissue
 Fibroblasts, resident macrophages and lymphocytes.
 The extracellular matrix, consists of the structural fibrous proteins (collagen, elastin), adhesive
glycoproteins (fibronectin, laminin, nonfibrillar collagen, tenascin, and others), and
proteoglycans.
 The basement membrane Is a specialized component of the extracellular matrix consisting of
adhesive glycoproteins and proteoglycans.
Types of inflammation:
1. Acute inflammation
 Rapid in onset (seconds or Minutes) of relatively short duration, lasting for minutes,
several hours, or a few days
 Its main characteristics are the exudation of fluid and plasma proteins (edema) and the
emigration of Leukocytes, predominantly neutrophils.
2. Chronic inflammation
 Is of longer duration
 Associated histologically with the presence of lymphocytes and macrophages, the proliferation
of blood Vessels, fibrosis, and tissue necrosis.
 Less uniform.
Acute Inflammation
 Acute inflammatory reactions are triggered by a variety of stimuli: Infections (bacterial, viral,
parasitic) and microbial
 Toxins Trauma (blunt and penetrating)
 Physical and chemical agents (thermal injury, e.g., burns or frostbite; irradiation; some
environmental chemicals)
 Tissue necrosis (from any cause) Foreign bodies (splinters, dirt, sutures)
 Immune reactions (also called hypersensitivity reactions)
5 Cardinal Signs of Inflammation
 Pain – dolor
 Heat – calor
 Redness – rubor
 Swelling – tumor
 Loss of function – Functio laesa
Inflammation
Nonspecific, defensive response of body to tissue damage.
5 CARDINAL signs:
1. Redness – RUBOR
2. Pain – DOLOR
3. Heat CALOR
4. Swelling- TUMOR
5. Loss of function – FUNCTIO LAESA


1.
3.
4.
Attempt to dispose of microbes, prevent spread, and prepare site for tissue repair
3 basic stages
Vasodilation and increased blood vessel permeability
Emigration
Tissue repair
KINIM SYSTEM – produces vasoactive systides
Stages of Inflammation
1. Vasodilation and increased permeability
Of blood vessels
Increased diameter of arterioles allows more blood flow through area bringing supplies and removing
debris
Increased permeability means substances normally retained in the blood are permitted to pass out –
antibodies and clotting factors Histamine, kinins, prostaglandins (PGs), Teukotrienes (LTS), complement
2. EMIGRATION:
Depends on chemotaxis
Neutrophils predominate in early stages but
Die off quickly Monocytes transform into macrophages
• More potent than neutrophils
• Pus-pocket of dead phagocytes and damaged tissue (absces)
s),
3. TISSUE REPAIR - plasmin
-
Collagen deposition
Repair of epithelium
New blood vessel formation (neovascularization)
The Kinin cascade:
Cytoly
-
Produces vasoactive systides increase vascular permeability and can activate the
complement cascade.
The Plasmin cascade:
-
Is important in remodeling extracellular matrix during wound healing and also can
activate complements.
-
Mast cells degranulate when they are activated releasing histamine which causes
increased vascular permeability.
Possible Outcomes of acute inflammation
1. Complete resolution
 Little tissue damage
 Capable of regeneration
2. Scarring (fibrosis)
 In tissues unable to regenerate
 Excessive fibrin deposition organized into fibrous tissue
Hypertropic scar – good arrangement of collagen
Keloid – disarrange collagen under microscope
Contractubex – for scar
3. Abscess formation occurs with some bacterial or fungal infections
4. Progression to chronic inflammation
Chronic Inflammation
 Lymphocyte, macrophage, plasma cell (mononuclear cell) infiltration
 Tissue destruction by inflammatory cells
Attempts at repair with fibrosis and angiogenesis (new vessel formation)
When acute phase cannot be resolved • Persistent injury or infection (ulcer, TB)
• Prolonged toxic agent exposure (silica) . Autoimmune disease states (RA, SLE)
The Players/Cells (mononuclear phagocyte system)
1. Macrophages
 Scattered all over (microglia, Kupffer cells, sinus histiocytes,

Alveolar macrophages, etc. Circulate as monocytes and reach site of injury within 24-48 hrs
and
 Transform Become activated by T cell-derived cytokines, endotoxins, and other products of
inflammation
2. T and B lymphocytes
 Antigen-activated (via macrophages and dendritic cells)
 Release macrophage-activating cytokines (in turn, macrophages release Lymphocyteactivating cytokines until inflammatory stimulus is removed)
3. Plasma cells
 Terminally differentiated B cells
 Produce antibodies
o IgM – mauna
o IgG – pinakamarami, galing na
o IgE – allergeic reaction
o IgA
o IgD
4. Eosinophils
 Found especially at sites of parasitic infection, or at allergic (IgE- mediated) sites
Eosinophil Function
• Leave capillaries to enter tissue fluid
Release histaminase
–slows down inflammation caused by basophils
Attack parasitic worms
Phagocytize antibody-antigen complexes done
Lymph Nodes and Lymphatics
Lymphatics drain tissues
Flow increased in inflammation
• Directs antigen to the lymph node where it is trapped
Toxins, infectious agents also to the node
Lymphadenitis, lymphangitis Usually contained there, otherwise bacteremia ensues
Tissue-resident macrophages must then prevent overwhelming infection
Lymph nodes and lymphatics act as filters of the extravascular fluids.
-they represent a secondary line of defense when the local inflammatory response fails to control the
injury
During inflammation the lymphatic
Flow is increased draining edema fluid from extravascular spaces. Lymph also may carry the causative
microbial or chemical agents and
Ath increased number of circulating
Lymphocytes.
Lymph channels and lymph nodes may become secondarily inflamed (lymphangitis and lymphadenitis).
Morphologic Patterns of Acute and Chronic inflammation
1. Serous Inflammation
 Watery, protein-poor effusion (e.g., Blister)
 triggered by agents causing mild damage to blood vessel walls and cytokines associated with
increased vascular permeability.
 production of exudate which is composed of watery fluid containing very little Protein.
 Depending on the inflammatory site the exudate accumulates serum in tissues (skin blister
caused by a mild burn) or in natural cavities like the pericardial sac, pleural or peritoneal
cavities (eg. Pleural effusion, ascitis) originated by the secretion of reactive mesothelial cells.
2. Fibrinous Inflammation
- Fibrin accumulation
- Either entirely removed or becomes fibrotic
o The injury is more severe and the Damage to blood vessel walls is more extensive with increased
vascular permeability.
o Plasma proteins including fibrinogen, leak from the blood vessels into interstitial spaces, and the
fibrinogen clots into fibrin.
o Histologically the exudate is composed of a mesh of eosinophilic strands and very few
neutrophils and sometimes as an amorphous clot.
Fibrinous exudate:
- May be degraded by fibrinolysis
- Eventually removed by macrophages restoring the normal tissue structure (resolution)
If the macrophages fail to completely remove the fibrin
- the latter is infiltrated by newly formed Blood vessels and fibroblasts resulting in Scar
formation (organization).
If the fibrinous exudate is present for example in the pleural cavity the process may end with the
formation of dense scar tissue that bridges and obliterates the pleural Cavity (fibrous adhesions).
3. Suppurative
Presence of pus (pyogenic staph spp.) Often walled-off if persistent
 Result of a severe inflammatory insult, and the resulting exudate is composed mainly by a large
number of neutrophils (purulent exudate).
 Many neutrophils die or degenerate in the inflamed area, releasing their lysosomal granules and
causing tissue necrosis.
 The gelatinous mixture of a large number of neutrophils, many of them degenerated, necrotic
tissue debris, and fibrinous material is called pus.

Some microorganisms such as Staphylococci are typically pus producers (pathogens).
Persistent suppuration : Abcess formation.
Persistent injurious: stimuli may Occasionally cause a chronic inflammatory response that is purulent
rather than not specific or granulomatous (persistent suppuration) like actinomycosis.
If the purulent inflammation is associated with a large amount of exudate and tissue necrosis, a cavity is
formed where the pus is collected (pyogenic abscess).
Abscesses may form in the parenchyma of major internal organs or soft tissues. They tend to:
1. Expand at the periphery by progressive necrosis and digestion of adjacent tissues
2. May drain spontaneously outside the body, or may burrow through adjacent tissues, emptying
its content into a natural cavity (e.g., pleural cavity) or the lumen of a nearby organ (sinus or
fistulous tract).
Patterns cnt
4. Ulceration
- Loss of mucosa
- Necrotic and eroded epithelial surface
- Underlying acute and chronic Inflammation
- Trauma, toxins, vascular insufficiency
Pseudomembranous inflammation
 Occurs mainly in the mucosal surface of the respiratory and alimentary tracts
 Caused by microorganisms such as Clostridium dificile and Corynebacterium diphtheriae.
(Woofing cough)
 The pseudomembrane (not a true tissue membrane) lies on the Mucosal surface of the affected
Organ (for example, intestine)
 Composed of fibrin strands, neutrophils, and necrotic epithelial cells.
 Pseudomembrane formation generally reflects the action of bacterial toxins upon mucosal
surfaces
Systemic manifestations of
Inflammation
Under optimal conditions, the inflammatory response remains confined to a localized area. In some cases local
injury can result in prominent systemic manifestations as inflammatory mediators are released into the
circulation.
.The most prominent systemic manifestations of inflammation are: The acute phase response ⚫Alterations in
white blood cell count (leukocytosis or leukopenia)
Fever
Sepsis and septic shock, also called the systemic inflammatory response, represent the severe systemic
manifestations of inflammation
The Systemic Inflammat
-
Takes place when the tissue injury is too severe or when a large number of
microorganisms are present at the inflammatory site.
-
Response requires the participation of organs and tissues that are remote from the site
of injury.
-
Known as the acute phase response, which is generalized and remarkably consistent.
Acute phase clinical reactions also occurs in chronic infections as well as in toxic, traumatic and immunological
disorders.
The acute response Increases production of effectors consumed during inflammation, such as granulocytes and
complement components.
The former is initiated mainly by the inflammatory cytokines IL1, TN alpha and IL6.
Systemic Effects
1. Acute Phase Reactants
These proteins are synthesized in the liver. IL-1 (Interleukin 1)
- Stimulates the synthesis of fibrinogen and C-reactive protein, while there is a decrease
in albumin synthesis.
- Especially useful in monitoring the – progress or detecting new bouts of acute
inflammation during the course of prolonged chronic conditions such as rheumatoid
arthritis.
The SAA (Serum Amyloid A) protein: - binds to the bacterial acting as opsonins. They can also fix complement.
In prolonged chronic inflammatory processes markedly elevated SAA may cause systemic amyloidosis.
2. Leukocytosis
• Leukocytosis
Elevated white blood cell count
Leukocytosis is usually selective.
Bacterial infection (neutrophilia)
⚫Parasitic infection/allergy (eosinophilia) Viral infection (lymphocytosis) – also seen in lymphoproliferative
disorders like CML, ALL
Leukocytosis results initially from the release of cells from the bone marrow induced by ILI and TNF.
• In chronic infection, proliferation of bone marrow precursors are also induced.
Certain infections, like typhoid fever or infections caused by certain viruses and protozoa, are associated with a
lower number of white cells (leukopenia)
-
The normal leukocyte count is between 5,000 and 10,000 cells/ mm3.
-
In acute inflammation the count usually climbs to 15,000 to 20,000 cells/mm3
(increased called neutropenia) and sometimes over 40,000 cells (leukemoid reaction – it
is not a cancer).
3. Fever
One of the easily recognized cytokine-mediated (esp. IL-1, IL-6, TNF)
⚫most prominent and readily measured systemic reaction of inflammation.
The thermoregulatory center is in the hypothalamus.
. Humans are very sensitive to the pyrogenic activity of bacterial endotoxins. Endotoxins stimulate the secretion
of IL-1, which in turn acts on the thermoregulatory center through the induction of local prostaglandin (PGE)
production.
Besides endotoxins, fever may be caused by gram-positive and negative bacteria, fungi and viruses.
4. Protein catabolism:
In certain long-standing chronic conditions (tuberculosis, brucellosis), IL-1 induces the catabolism of proteins in
the host, associated with a net loss of nitrogen, loss of body mass, and muscle wasting.
The proteins particularly involved are those containing phenylalanine, tyrosine and tryptophan, which are
utilized in the synthesis of antibodies and interleukins.
Other acute-phase reactions include:
1. Anorexia-cytokines act on brain cells
2. Skeletal muscle protein degradation – cytokine induced
3. Hypotension – an effect of septic shock
Granulomatous inflammation
A granuloma consists of localized, tight aggregates of epithelioid cells(activated macrophages).
 Develop after prolonged antigenic stimulation.
 Epithelioid cells are large, with a pale, granular eosinophilic cytoplasm resembling squamous
cells. Often granulomas are surrounded by a collar of lymphocytes and occasionally plasma cells
There are two types of granulomas:
1.Foreign body granulomas caused by relatively inert foreign material that cannot be digested, causing
activation of Macrophages.
2.Immune granulomas, which develop in the presence of indigestible microorganisms (M tuberculosis)
by cell-mediated immune response (adaptive or specific immune response).
SEPSIS:
• Sepsis is a potentially life- threatening condition that occurs when the body’s response to an infection
damages its own tissues.
• When the infection-fighting processes turn on the body, they cause organs to function poorly and
abnormally.
• characterized by excessive inflammation (sometimes resulting in a cytokine storm) may be followed by
a prolonged period of decreased functioning of the immune system.
TIME
Sepsis
Arises when the body’s response to an infection injures its own tissues and organs. It may lead to shock, multiple
organ failure, and death, especially if not recognized early and treated promptly
STAGES:
1. From a local infection to a general inflammation
Stop sepsis save lives
A local infection-e.g. in the lung – over- comes the body’s local defense mechanisms. Pathogenic germs
and the toxins they produce leave the original site of the infection and enter the circulatory system.
2. Organ dysfunction – severe sepsis
This leads to a general inflammatory response: SIRS
Systemic inflammatory response syndrome
The function of individual organs starts to deteriorate and may completely fail.
Sepsis starts with the onset of at least one
New organ dysfunction.
MCQ – IN TISSUES
LESSON 2 AND 3 – IDENTIFICATION