General Pathology

By
Faisal Mehboob

Causes of Cell injury

Hypoxia
Infection
Immunologic reaction
Congenital disorders
Chemical injury
Physical form of injury like
trauma
Nutritional or vitamin
imbalance

Necrosis

localized death of a living tissue. Types are

Coagulative necrosis (common, occur due to ischemic
injury like infarct) common in HEART, KIDNEY, LIVER
Liquefaction necrosis (occur from cellular destruction by
hydrolytic enzymes) common in ABCESSES,BRAIN
INFARCT
Caseous necrosis (Combination of Coagulative &
liquefacted necrosis) occur in TUBERCULOSIS
Fat necrosis (caused by action of lipases on adipocytes)
Fibrinoid necrosis ( a form of necrotic tissue ,
histologically resembles to fibrin.) occur in immunological
injury
Gangreneous necrosis (Gross term , use to describe dead
tissue) *Dry gangrene (has coagulative necrosis) *wet
gangrene (has liquafective necrosis)

Apoptosis

Specialized form of programmed cell death without

an inflammatory response.
It is an active process regulated by Genes and
involve RNA and protein syn.
Stimulus for apoptosis include injury and DNA
damage, lack of hormones or growth factor.
Apoptosis is regulated by genes bcl-2 (which
inhibit apoptosis) & Apaf-1 (which stimulates
apoptosis)
e.g Embryogenesis (organogenesis & development)
Hormone dependent apoptosis (menstural cycle)

Difference

Sub-cellular response to injury

Adaptation (atrophy,
hypertrophy, hyperplasia,
metaplasia,dysplasia)
Reversible injury
Irreversible injury
Cell death (apoptosis,
Necrosis)

Cell adaptation
Atrophy (*dec in cell size * dec in functional
ability *cause is immobilization )
Hypertrophy (*inc in cell size* cause is inc syn
of intracellular components)
Hyperplasia (*inc in number of cells *cause is
compensatory mechanism *some cells not exhibit
hyperplasia like nerves, cardiac cells)
Metaplasia (*reversible change of one cell type to
another ususally in response to stimulus e.g
broncial epithelium undergoes squamous
metaplasia in response to irritation of tobacco)
Dysplasia (*abnormal proliferation of cells that is
charcterized by changes in cell size , shape)

Intracellular Accumulations
Lipids can accumulate intracellularly include
triglycerides, cholesterol.
Protein can accumulate in proximal renal tubules
in proteinuria and can form Russell
bodies(intracellular accumulation of
immunoglobulin)
Glycogen storage disease
Exogenous pigments includes *pigmentation of
lungs
Endogenous pigments include *Melanin *
Hemosiderin *Bilirubin

Inflammation

Definition
Inflammation is a protective response of the
body against noxious or injurious stimulus.
The signs of inflammaiton are
Heat (color)
redness (rubor)
swelling (tumor)
pain (dolor)
loss of function

Differences
Acute inflammation
1. Fast; min or hours
2. mainly neutrophils
3. usually mild injury
4. Prominent signs

Chronic inflammtion
1. slow; days
2. monocyte /macrophages
3. severe or progresive
4. Less prominent signs

Steps of inflammatory response

Recognition of injurious agents
Recuirtment of leukocytes
removal of the agents
Regulation of response
Repair

Differences
Transduate
Found in earliest phase
of inflammtion
Results from
intravascular
hydrostatic pressure
Protein poor <2gm%
Specific gravity <1.012
Neutrophils absent
Fibrinogin absent

Exudate
It overshadows the
tranduate phase of infl..
Results from vascular
permeability
Protein Rich 2-4gm%
Spe gravitiy >1.020
Neutrophils present
Fibrinogin present

Acute Inflammation
Vascular changes
Vasodilation (induce by histamine)
Increased vascular permeability(by histamine and kinins)
Increase adhesion of leukocytes
Migration of leukocytes
Cellular changes
Margination & Rolling (leukocyte accumulation at the periphery)
Adhesions
Transmargination
Chemotaxis

Outcomes of acute inflammation

imp points cell der Chemical mediators

vasoactive amine- histamine & serotinin: main

funciton is vasodilation and inc. permeability.

Arachdonic acid metabolites- prostaglandins &

leukotriens: involve in vascular reaction and there
antagonist is lipoxins

Cytokines: they are involve in leukocyte recruitment

and migration

Imp points :: plasma derived chemical

mediators

Kinin : mediate vascular reaction and pain

Coagulation proteins : triggers clotting and

activates fibrinolytic system.

Complement protein : Activation of

complement system by microbes leads to
generation of multiple breakdown products.

Chronic Inflammatin

Prolonged host response to persistant stimulus.

Caused by microbes which resist elimination,
immune responses.
Charecterized by persistant inflammation ,
tissue injury
Chemical mediators of chronic inflammation
are * Macrophages* lymphocytes *plasma cells
Mediated by cytokines which are syn by the
macrophages and the lymphocytes.

Granulomatous Inflammation

Pattern of chronic inflammation characterized by ''

aggregates of activated macrophages with scattered
lymphocytes''.
Granulomas can form under three settings
with persistant T-cell response to certain microbes
may also form in immune-mediated inflammatory
diseases like Crohn disease
they are also seen in a disease with unknow etiology
called sarcoidosis, and they develop in response to
relatively inert foreign bodies , so called FOREIGN
BODY GRANULOMAS.

Morphology of Granulomatus
inflammtion
Soft tubercle (which have central ceasous
necrosis) e.g TB
Hard tubercle (which have no central
ceasous necrosis & has hard consistency)
e.g sarcoidosis
Gumma (has central Granulomatous
necrosi) e.g syphilis

Morphological patterns in acute and

chronic inflammation
(serious faysal, support members of history interest)

Serous inflammation(skin blister resulting

from burn)
Fibrinous Inflammation (in pericardium or
pleura)
Suppurative inflammation (in appendicitis)
Membranous inflammation (in diphtheria)
Histolytic inflammation (in typhoid)
Interstitial inflammation (in viral infections)

Repair

Repair by connective tissue

GDAR

Granulation tissue formation

Deposition of extracellular matrix
Angiogenesis PMPM
proteolytic degradation of basement membrane,
migration of endothelial cells
proliferation of endothelial cells
maturation of endothelial cell
Remodeling

Steps of
Angiogenesis

Differences
Primary Union
No wound contraction
less inflammatory
reaction
less scar formation
Rapid healing
small amount of
granulation tissue

Secondary Union
Wound contraction
more intense
inflammatory reaction
More scar formation
Slow healing
large amount of
granulation tissue

Mechanism of wound healing

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Regenration of parenchymal cells

Migration and proliferation of parenchymal and
connective tissue cells.
Syn of extra cellular matrix proteins
Remodeling of connective tissue parenchymal
components.
Collagenization of wound strength

Hemodynamic
Disorders

Edema
Edema is the result of the movement of fluid from the
vasculature into the interstitial spaces. This fluid may be
protein poor (transduate) or protein rich (exudate).
Causes
Inc hydrostatic pressure e.g heart failure
Impaired venous return
Arteriolar dilation
Reduced plasma osmotic pressure (Hypoprotenemia)
Lymphatic obstruction e.g iflammation or neoplasia
Sodium retention e.g renal failure
Inflammation

Morphology ss PPP c
Subcutaneous edema occurs in Congestive heart
failure.
Sacral edema occurs in patients of CHF
<Dependent edema> subcutaneous edema , sacral
edema , are referred to as dependent edema.
Periorbital edema occurs in renal dysfunction
Pitting edema ,,, in this edema a pitted depression
form when finger pressure is applied.
Pulmonary edema occurs in left ventricular failure.
Cerebral edema occurs in brain trauma

Types
Generalized edema
1. Congestive heart failure
2. Nephrotic syndrome
3. Cirrhosis of liver
4. Protein malnutrition
Localized edema
1. Venous obstruction due to thrombuss
2.. Lymphatic obstruction due to neoplasia
3. Inc vascular permeability due to chemical mediators of
inflammation.

Hyperemia or Congestion
Local inc vol of blood caused by dilation of small
vessels is term as Hyperemia or congestion.
Types
o Active Hypermia (due to augmented arterial flow)
o Passive Hypermia (due to diminsh venous outflow)

Hemorrhage
Rupture of blood vessels with loss of blood is term as
Causes.

Causes
Types

Trauma
Hemorrhagic diathesis
Hypertension
Atherosclorosis

External Hemorrhage
Internal Hemorrhage
Hematoma
Hemorrhage into the body
cavities.
Petechiae
Pupura

Thrombus
Formation of clotted mass of blood into the blodd
vessels
Consequences.
Embolus formation
Infections
Factors which are responsible for thrombus
formaiton
Endothelial injury
Hypercoagulability
Autonomy

Fate of thrombosis
May propagate & may cause obstruciton of some critical vessels
May embolize
May be removed by fibrinolytic activity
May undergo organization
Organized thrombi may become recanazlized
Center of thrombus may undergo enzymatic digestion.

Embolism
Occlusion of some parts of CVS by impactin of some
mass (embolus) tranported to the site thru blood
stream.
Fate of venous emboli
It can result in pulmonary infarction.
Fate of arterial emboli
It can result in myocardial or cerebral infarction.

Fat embolism
Presence of minute fat glbultes in circulation.
Causes
Fracture of shaft of long bones.
Soft tissue trauma
Burns
Fat embolism syndrome
It occurs in 1% of individuals following skeletal injuries
Imp point :: Caisson Disease is a disease charecterized by specific
clinical manifestations that results from sudden lowering of
atmospheric pressure.
I

Infarction
An area of ischemic necrosis within a tissue or an
organ produced by occlusion fo either its arterial
supply or venous drainage.
Causes
Balloning of ateroma
Twisting of vessels
Thrombotic occlusion
Embolic occlusion

Types of infarcts.
White (anemic) infarct (caused by occlusion of arterial
supply)
Red (Hemorrhagic) infact (caused by venous drainage)
Fate of infarct.
Most infarcts are replaced by scar tissue
When infarct is produce by a septic embolus containg
microorganism infarct converts into an abcess.

Shock
Widerspread hypoperfusion of cells and tissues due to
reduction in blood volume or cardiac output is term as
shock
Types.
Cardiogenic shock
Hypovolemic shock
Septic shock
Neurogenic shock
Anaphylactic shock

Stages of shock
Non-progressive state of shock
Activation of neurohumoral compensatory
mechanism to preserve the perfusion of vital organs.
Progressive state of shock
Uncorrected shock passes to progressive stage
characterized by hypoxia of vital organs.
Irreversible stage of shock
Severe cellular and tissue injury

Immunity

General Features
Immune system is refered to a system composed of
specialized cells that fight against disease producing bacteria
and toxins
Classification
Acquired (specific) immune system
Humoral components ( composed of specific antibodies)
Cellular components ( composed of sensitized T lymphocytes)
Innate (non specific) immune system
Cellular components(composed of neutrophils, macrophages,
langerhens cells)
Non-cellular components (composed of skin, acidity of
stomach & enzyme of GIT.

Hypersensitivity reaction
Also term as immune mediated tissue damaging reactions
Types of hypersensitivity reactions
Type 1 Hypersensitivity(anaphylactic type)
A rapidly occuring reaction
Follows combination of an offending antigen with antibody
IgE, which previously bound to the surface of mast cells
and basophils.
Phases
a. Immidiate phase (occur in 5-30 min, mediated by
histamine)
b. Late phase (occurs in 2-8 hours, mediated by Heparin
neutral protein e.g Tryptase)

 Cells of type1 Hypersensitivity

a. Mast cells
b. Basophils
Antibodies of type1 Hypersensivity
a. IgE in human
b. IgG in other species
Proteolytic disorder are (allergies, asthma)
Type 2 Hypersensitivity(Anti-body dependent)
A hypersensitivity reaction in which antibodies are formed
against target antigens that are either normal or altered cell
membrane components
Antidobodies of type 2 are IgG, igM
Proteolytic disorder are (Autoimmune hemolytic anemia,
goodpasture syndrome)

 Type 3 Hypersensitivity (immune complex mediated) IgG

Deposition of antigen antiboy complexes => complement
activation => recruitment of leukocytes by complement
products and Fc receptors => release of enzyme and other
toxic molecules.
Prototypical disorder are *systemic lupus erythematous,
serum sickness, glomerulonephritis, arthus reaction.
Type 4 Hypersensitivity reacitons (cell mediated) Th1 cells
Activated T-lymphocytes 1. release of cytokines ,
inflammation or macrophage activation 2. T.cell-mediated
cytotoxicity
Protypical disorders are Contact dermatitis, multiple
sclerosis, type1 diabetes, TB

Immune deficiencies
Primary immunodeficiencies
1. X-linked(congenital)
2. Thymic hypoplasia
3. Isolated deficiency of immunoglobulin A
4. Immunodeficiency with thrombocytopenia
Secondary immunodefeciencies
1. AIDS
2. Sarcoidosis
3. Infections
4. Malnutrition
5. Renal diseases

Autoimmunity
An immune reaction against self antigens
A disease produced by immune system against self
antigens is term as autoimmune disease.
Examples
Systemic lupus erthematosus
RA
Spondylo-arthropathies
Systemic sclerosis

Amyloidosis
Deposition of amyloid (an abnormal proteinesious
substance) b/w cells in many tissues and organs in various
clinical disorders.

Types of Amyloidosis
1..Systemic (Generalized)Amyloidosis
*Immunocyte dyscrasias with amyloidosis
*Reactive systemic amyloidosis
2..Localized amyloidosis
*Senile cardiac amyloidosis
*Senile cerebral amyloidosis
*Endocrine amyloidosis

 Imp point
Amyloidosis is diagnosed histologically by Congo red
staining

Neoplasia

Benign Tumor

Malignant tumor

Localized
Not spread
Patient survive

Invade
Destroy adjacent structures
Spread to distant sites to
cause death.

Nomenclature of
benign tumors

Nomenclature of
malignant tumors

Nomenclature of benign
mesenchymal tumors
These tumors are named by
attaching suffix OMA to the cell
type from which the tumor arises.
E.g Fibroma, chondroma
Nomenclature of benign
epithelial tumors
1. On the basis of appearance
(papiloma)
2. On the basis of cell of origin
(adenoma)

Nomenclature of malignant
tumor
These tumors are named by
attaching suffix SARCOMA to
the cell type of which they are
composed. (fibrosarcoma)
Nomenclature of malignant
epithelial tumor
1. On the basis of appearance
(papillary carcinoma)
2. On the basis of cells of origin
(renal cell carcinoma)

Nomenclature of special tumors

Poorly differentiated carcinoma
Mixed tumors
Teratoma
Hemartoma
Choristoma
Some malignant tumors bearing benign tumors

Molecular basis

Normal
cell

DNA
damage

Expression of
altered gene
products and loss
of regulatory gene
products

Malignant
neoplasm

Mutation in
the genome of
somatic cell

Risk factors for breast cancer

Morphology of invasive ductal carcinoma

Carcinogenic agent
Chemical carcinogens
Direct acting carcinogens (*alkylating agents like antineoplastic
drugs {nitrosoureas})
Indirect acting carcinogens (*polycyclic and heterocyclic aromatic
hydrocarbons *aromatic amines *natural plants and microbial
production)
Radiation carcinogens (*ultraviolet rays of sunlight *x-rays *rays
produce by nuclear fission *radio nucleotides)
Viral carcinogens
RNA oncogenic viruses (*Human Tcell leukemia virus type 1 *IL-2
and IL-1)
DNA oncogenic viruses (*Human papilloma viruses *Epstein Barr
viruses *Hepatitis B virus )

Clinical aspects
Paraneoplastic syndromes (*Cushigs syndrome, *Hypercalcemia, Carcinoid
syndrome, nonbacterial thrombotic endocarditits)
Manifestations of due to endocrine neoplasms. (*adenoma fo B cells of
pancreas produce *adenoma of adrenal cortex elaborate aldosterone that causes
sodium retention, hypertension and hypokalemia)
Cancer cachesxia (terminal stage of advanced cancers, in which pts suffer
from progressive loss of body fats and lean body mass, accompanied by
profound weakness, anorexia, anemia and intercurrent infections.)
Ulceration (may produce bleeding or secondary infections)
Manifestation due to location (benign or malignant neoplasms impinge on
adjacent structure due to their location)
Acute emergencies due to infarction and rupture (infarction and rupture for
a neoplasm may give rise to acute medical and surgical emergencies)

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