Hypertrophy
1. ↑ size of cells & organ.
2. Occurs: where cells
cannot divide - Striated m.
3. No formation of new cells
(cell arrest)
4. Physiologic: Increase in
muscle size with exercise.
5. Cells become larger.
Cardiac & skeletal striated
m.
6. No cell swelling:
- ↑ protein in cellular
components
- no ↑ in cellular fluid
7. No ↑ in no. of cells!!!
1. PHYSIOLOGICAL
i. Skeletal muscles
(weight lifters, athletes)
ii. Hormonal stimulation
— Uterus smooth muscles
during pregnancy – [Absence of organ in paired
estrogen.
2. PATHOLOGICAL
i. Myocardial
hypertrophy:
Hypertension
Valvular stenosis
Hyperplasia Atrophy Metaplasia
- ↑ in NUMBER of cells Is adaptive and Mature differentiated
- Restricted to cells capable REVERSIBLE adult cell type is replaced
of undergoing mitosis condition by another adult
Skin epidermis: Squamous epi differentiated cell type.
GIT: Columnar intestinal epi Results in a Etiology:
Glands: Cuboidal epi
decrease in cell Response to an adverse
Physiological hyperplasia
size & organ environment
- Enlargement of uterus &
 REVERSIBLE
breast in pregnancy.
 response to chronic
irritation &
inflammation
PHYSIOLOGICAL - ↑ level - Disuse atrophy: In i. Prolonged irritation in
of a normal stimulus paralysis & smokers: Pseudostratified
(hormonal) decrease workload. columnar bronchial
(i) In liver regeneration after - Degeneration epithelium - squamous
injury. atrophy (Multiple
epithelium.
(ii) A compensatory response. Sclerosis)
ii. Squamous epithelium
- Nerve (lower esophagus) - gastric
organ or after partial resection] denervation.
iii. Wound healing: Scar tissue columnar epi
- Ischemic atrophy (HCl acid reflux – Barrett
formation.
(kidney, heart) esophagus)
PATHOLOGICAL
- Pressure atrophy
Response to an excessive iii. Chronic infections -
stimulation. - Malnutrition
Worms
(i) Thyroid gland (goiter) — atrophy (starvation
iodine deficiency & cachexia)
(ii) Hormonal Stimulation - Loss of endocrine
– Uterine endometrial stimulation (Uterus
hyperplasia: ↑ estrogen levels. & breast:
– Benign prostatic hyperplasia: Menopause)
Androgen stimulate - Brain atrophy:
(iii) Excessive growth factor Alzheimer’s disease
stimulation in viral warts (HPV)
 Dysplasia Aplasia Hypoplasia Anaplasia
Deranged cell Failure of Failure of organ to A qualitative Metaplasia
growth with development of attain full size. alteration of cell Replacement of
alteration in size, tissue or organ differentiation. an adult
shape & (IUL) differentiated
orientation of
epithelial cells with
cell into
loss of another adult
differentiation. differentiated
* A STRONG cell.
PRECURSOR OF Reversible
CANCER!!! change
- asso. with chronic
irritation or ↓
inflammation
Grossly: Not much Aplastic organs are • Less severe Anaplastic cells:
can be appreciated. either totally absent abnormality than i. Typically poorly Dysplasia
or represented by aplasia. differentiated or Loss of cellular
Microscopically: small mass of • Rudimentary undifferentiated. uniformity &
i. Cellular atypia: fibrous or fatty organs are smaller ii. Exhibit cellular tissue
Cellular tissue containing a than normal. pleomorphism:
pleomorphism & architecture
few rudimentary • Lack full - Variation in size
hyperchromasia. cells. complement of & shape of cells.
ii. Loss of ↓
cells, so function
uniformity of may be reduced or
individual cells compromised. Neoplasia
iii. Loss of New growth
architectural Irreversible
orientation or
polarity.
iv. Mitotic figures
may be seen.
Cervical dysplasia Paired organs – Unilateral renal
adrenals, kidneys, hypoplasia
lungs
 Coagulative Necrosis
• Seen in hypoxic or ischemic
(infarction) death of all tissues
except brain
• Denaturation of proteins is the
dominant process
• As enzymatic proteins get
denatured  blocking of enzymatic
lysis
• Affected tissue is firm & shows
preservation of basic outline of cell
• Dead cells are removed later by
phagocytosis or heterolysis
Liquefactive Necrosis
• Dominated by enzymatic
digestion
of dead cells with total loss of
structural details
• Seen in focal bacterial infections
& in some fungal infections
• Hypoxic death in BRAIN is
always liquefactive
• Cells are completely digested &
tissue becomes viscous liquid
mass; in abscesses, it becomes
creamy yellow pus
Caseous Necrosis
• found in foci of TB infection in
association with Mycobacteria
• due to the presence of mycolic
acids within their cell membranes.
• Appears cheese like on gross
examination
• Microscopically shows
fragmented cells with amorphous
granular pink appearance
 Gangrenous Necrosis Fat Necrosis Fibrinoid Necrosis
• limb which has lost blood supply • focal areas of fat destruction • Occurs in immune reactions in
& undergoes coagulative necrosis (1) Traumatic (breast) which immune complexes of
• DRY gangrene – Affected limb (2) Enzymatic antigens & antibodies are deposited
is completely black in color &  Seen in acute in vessel wall
wood-like hard pancreatitis • The deposits damage the vessel
• WET gangrene – when bacterial  Activated pancreatic wall & produce a bright pink
infection is superimposed, enzymes liquefy fat cell amorphous appearance called
appearance changes to m. & split triglyceride fibrinoid (– fibrinlike)
liquefactive necrosis esters
 Released fatty acids • Example – polyarteritis nodosa
combine with Ca to
form chalky white
flakes (saponification)
 APOPTOSIS
Definition
• “programmed cell death (PCD)” designed to
eliminate unwanted cells through activation of non-
lysosomal endogenous endonuclease which digests
nuclear DNA into smaller DNA fragments.
• Cellular suicide mechanism
• May be physiological or pathological
Physiological Examples
Intrinsic Pathway/
– During embryogenesis Mitochondrial Pathway
– Involution of hormone dependent tissues after
hormonal withdrawal; eg. in uterus after menopause
– Cell loss in proliferating cell populations
– Elimination of potentially harmful self-reactive
lymphocytes
– Death of host cells that have subserved their useful
purposes; neutrophils after acute inflammation
Pathological Examples
• DNA damage
• Accumulation of misfolded protein
• Cell death in certain infections (viral) Extrinsic Pathway
• Pathologic atrophy in parenchymal organs after duct • Is activated by engagement of plasma m. death receptor
obstruction • Fas binds with fasL
• Fas associated death domain (FADD) activates
• DNA damage-mediated apoptosis: • Procaspase-8 is converted into caspase-8

• Radiation/chemotherapy induced apoptosis • Initiator sequence begins

of cancer cells Execution Phase

• Intrinsic / extrinsic - converge at activation of execution pathway
• Important Executioner caspases are caspase-3, caspase-6
MORPHOLOGY • They in turn activate DNAase
• Break down of nuclear matrix
• Cell shrinkage • Proteolysis of cytoplasmic proteins

• Smaller size, dense cytoplasm, tightly

packed organelles
• Chromatin condensation
• Peripheral aggregation of chromatin,
breakup of nucleus
• Cytoplasmic blebs & Apoptotic bodies formation
• Phagocytosis of apoptotic bodies by
macrophages
• No inflammation
 ACUTE INFLAMMATION
Inflammation: dynamic response of vascularized
tissue to injury.
Appearance of Inflammation:
Flush: Red spot - capillary dilatation
Flare: Red area - arteriolar dilatation
Weal: Swelling - exudation, oedema
Cardinal Signs of Inflammation:
 Calor : Warm – Hyperemia
 Rubor : Redness – Hyperemia
 Dolor : Pain – Nerve, Chemical med
 Tumor : Swelling – Exudation
 Functio laesa : Loss of function
Acute - Minutes to days
Characterized by Hyperemia & exudation.
PMN’s – Neutrophils, (eosinophils Basophils)
Chronic - Weeks to Months - Years
Characterized by Hyperemia & exudation.
MN’s - Lymphocytes & Macrophages
3 Major Components:
1. Alterations in vascular caliber  lead to a
local ↑ in blood flow (vasodilation).
2. Structural changes in the microvasculature 
permit plasma proteins to leave circulation.
3. Emigration of leukocytes from
microvasculature & accumulation in focus of
injury.
Vascular Changes
1. Changes in Vascular Flow & Caliber
 Transient vasoconstriction of arterioles,
followed by vasodilation.
 Local ↑ in blood flow  redness (erythema)
& warmth.
 Then, exudation of protein rich fluid into
extravascular spaces.
 ↑ blood viscosity, small b.v. are packed with
RBCs  STASIS
 Margination of leukocytes, followed by
emigration.
2. Increased Vascular Permeability (Vascular
Leakage)
Leukocyte Cellular Events
1. Migration & Rolling
 Leukocytes settle out of central column,
marginating to vessel periphery.
 Tumble on endothelial surface, transiently
sticking along the way
 rolling (pavementing)
 Mediated by binding of complementary
adhesion molecules on leukocytes &
endothelial surfaces
2. Adhesion & transmigration b/w endothelial cells
 Leukocytes firmly adhere to endothelial
surface (adhesion).
 They crawl b/w cells, through basement m.
into extravascular space (diapedesis).
3. Migration in interstitial tissue towards a
chemotactic stimulus [Chemotaxis &
Activation]
 After extravasation, leukocytes emigrate
toward site of injury along a chemical
gradient: chemotaxis.
 Chemotactic agents – endogenous/
exogenous:
Soluble bacterial products, Complement
system, products of Arachidonic Acid (AA)
pathway metabolism & cytokines.
 They bind to specific receptors on leukocyte
cell surface & stimulate the cell to move.
 They also induce leukocyte activation.
Phagocytosis
1. Recognition & attachment of particle to
ingesting leukocyte
2. Engulfment with subsequent formation of a
phagocytic vacuole
 3. Killing & degradation of ingested material
Defects in Leukocyte Function:
 adhesion – bacterial infections
 chemotaxis / phagocytosis
– Chediak Higashi syndrome
 microbicidal activity
– chronic granulomatous disease
HARMFUL EFFECTS
1. Digestion of Normal Tissues
o Lysosomal enzymes (collagenases &
proteases) digest normal tissues
destruction  vascular damage
2. Swelling
o Acute epiglottitis in children due to
Hemophilus influenzae,
o Acute meningitis  raise intracranial
pressure & ischemic damage
3. Inappropriate Inflammatory Response
BENEFICIAL EFFECTS
o Dilution of toxins, produced by bacteria,
allows them to be carried away in lymphatics.
o Entry of antibodies. ↑ vascular permeability
allows antibodies to enter extravascular space.
o Drug transport. Fluid carries drugs
(antibiotics) to site of bacteria multiplying.
o Fibrin formation, from exuded fibrinogen
may impede movement of micro-organisms,
trapping them & help phagocytosis.
o Delivery of nutrients & oxygen,
inflammatory cells which have high metabolic
activity  ↑ fluid flow thru’ the area.
o Stimulation of immune response. The
drainage of this fluid exudate into lymphatics
allows antigens to reach local LN where they
may stimulate immune response.
o Exocytosis. Neutrophils & macrophages
discharge lysosomal enzymes into ECF
assisting in digestion of inflammatory
exudate.
SYSTEMIC EFFECTS
o Pyrexia - Polymorphs & macrophages
produce endogenous pyrogens  act on
hypothalamus to set thermoregulatory
mechanisms at ↑ T.
o Constitutional symptoms - malaise,
anorexia, nausea, weight loss.
o Reactive hyperplasia of reticulo-endothelial
system - Local / systemic LN enlargement,
splenomegaly (malaria, infectious
mononucleosis)
Hematological Changes
 ↑ Erythrocyte sedimentation rate (ESR)
 Leukocytosis,
 Anemia:
 Blood loss in inflammatory exudate
(ulcerative colitis)
 Hemolysis due to bacterial toxins
 Anemia of chronic disorders' due to
toxic depression of the bone marrow
SUPPURATION
 Formation of pus, a mixture of living, dying
and dead neutrophils & bacteria, cellular
debris and sometimes globules of lipid
 Once pus begins to accumulate in a tissue, it
becomes surrounded by a 'pyogenic
membrane' consisting of sprouting
capillaries, neutrophils & fibroblasts.
 Forms an abscess, and bacteria within
abscess cavity are relatively inaccessible to
antibodies & to antibiotic drugs (acute
osteomyelitis).
FATE OF ABSCESS
 Abscess cavity collapses & is obliterated by
organization & fibrosis, leaving a small scar.
 Deep-seated abscesses sometimes discharge
their pus along a sinus tract (fistula).
ULCERS
 local defect, or excavation, of surface of an
organ or tissue that is produced by sloughing
(shedding) of inflamed necrotic tissue
 CHRONIC INFLAMMATION
Features (Chronic vs Acute)
Chronic Acute
- Sequence of continuing inflammation - vascular changes
- Infiltration by mononuclear cells: - edema
Macrophages - infiltration: neutrophilic
Lymphocytes infiltrate
Plasma cells
- Tissue injury: Products of inflammation
- Healing: Angiogenesis & fibrosis
SYSTEMIC EFFECTS OF INFLAMMATION

CHRONIC GRANULOMATOUS
INFLAMMATION
- Granuloma: a form of chronic inflammation
characterized by focal collection of activated
macrophages & T lymphocytes due to
persistence of a non-degradable / non-
infectious agent accompanied by active cell
mediated hypersensitivity.
Granuloma Evolution Sequence

Hallmarks of Chronic Inflammation

SYSTEMIC EFFECTS
Activated T-Lymphocytes Release
1. fever & weakness
2. anemia
3. lymphocytosis
4. elevated ESR
5. chronic granulomatous inflammation
6. healing: Fibrosis & collagen
OUTCOME
COMPOSITION
PATHOGENESIS
 WOUND HEALING
Factors influencing Wound Healing:
1. Systemic Factors
Nutrition: protein, vitamin C
Metabolic status: diabetes mellitus
Circulatory status: inadequate blood supply;
arteriolosclerosis, retard venous drainage
Hormones: glucocorticoids (inhibits wound)
healing by impairing collagen synthesis
2. Local Factors
Infection: septic wound
Mechanical factors: mobilization
Foreign bodies: suture material, bone pieces,
glass pieces
Size, location & type of wound
Complications in Wound Repair
(1) Deficient scar formation: wound dehiscence,
ulceration
(2) Excessive formation of repair components:
Keloid, Hypertrophied Scar,
exuberant granulation tissue / proud flesh,
desmoid / aggressive fibrosis
(3) Formation of contractures:
after serious burns-compromise joint
movement

Development of fibrosis in chronic inflammation.

 Persistent stimulus of chronic inflammation
activates macrophages & lymphocytes
- production of GF & cytokines
 ↑ synthesis of collagen
 Deposition of collagen
 enhanced by ↓ activity of
metalloproteinases
 Calcification
1. Dystrophic Calcification
Calcification in degenerated or dead necrotic tissue:
Hyalinized scars
Degenerated foci: Leiomyoma
Tissue necrosis: Caseous & Fat Necrosis
Microscopic cell injury: Chronic valvular heart disease
PATHOGENESIS:
 Activated phosphates bind Ca2+ ions to
phospholipids in cell membrane.
 Basophilic calcium salt deposits aggregate in
mitochondria, progressively thru’out cell.
 Formation of calcium phosphates
 Serum calcium: Not elevated
 Combination of fat & caseating necrosis
 Focal deposition of hydroxyapatite crystals in
previously damaged tissue
Calcification in Dead Tissues:
MORPHOLOGY:
2. Metastatic Calcification
- Systemic mineral imbalance  elevation of Ca
levels in blood & all tissues
ETIOLOGY:
(i) Disturbances in calcium/phosphorus
metabolism
(ii) HYPERCALCEMIA:
 Persistently elevated Ca levels
 Primary Hyperparathyroidism
 ↑ parathormone secretion
Pigmentation
Exogenous Pigments
1. Carbon (Coal Dust) & Anthracosis
Pathog: On inhalation enters alveolar macrophages
Transported to regional tracheobronchial LN
Blackening: Lung & affected LN
Complic: i. Coal Miner’s lung or pneumoconiosis
ii. Lung fibrosis
iii. Emphysema
2. Tattoo
Pathog: Intro of pigment into subQ tissue
Taken up by dermal macrophages
No inflammatory response
Endogenous Pigments
1. Lipofuscin (‘Wear & Tear’ pigment – insoluble)
 Composed of lipids & phospholipids coupled
with protein.
 Indicates free radical injury coupled with lipid
peroxidation.
 Yellow- brown perinuclear pigmentation
 Liver & heart muscle in aged patients
 Cancer & malnourished patients
2. Melanin (brown-black)
 Derivative of tyrosine
 Present in melanocytes in epidermis
3. Hemosiderin
 Yellow-brown derived from hemoglobin
breakdown
 Stored iron in body cells coupled with
apoferritin
Pathog: Excessive production: Hemorrhage
Hemosiderin granules in mononuclear cells
Does not impair cell function
Diagnosis:
 Prussian Blue Stain Reaction:
Colorless potassium
 ferrocyanide-converted to blue-black ferric
ferrocyanide
 Iron pigment: Coarse golden brown in
cytoplasm
i. Excess of dietary iron
ii. Hemolytic anemias
iii. Repeated blood transfusion
4. Bilirubin (pigment in bile)
 Derived from hemoglobin & contain no iron.
 Clinical disorder: Jaundice
 NEOPLASIA
An abnormal mass of tissue, the growth of which
exceeds & is uncoordinated with that of normal
tissues & persists in the same excessive manner
after cessation of stimuli which evoked the
change.
 Progressive, Purposeless, Pathologic, Proliferation
 Uncontrolled cell division
Pathogenesis (Progressive DNA
Damage!!!)
Exceptions: Leukemia, Lymphoma, Glioma,
Hepatoma, Melanoma, Seminoma
Benign / Malignant Neoplasms
2 basic components:
1. proliferating neoplastic cells that constitute their
parenchyma.
2. supportive stroma made up of CT & b.v.
BIOLOGICAL FEATURES
1. Differentiation & Anaplasia
 Well differentiated/Low grade
 Moderately differentiated / Intermediate
grade
 Poorly differentiated/ High grade (poor
prognosis)
2. Rate of Growth
 Benign tumors grow slowly.
 Malignant tumors grow at a faster rate,
spread locally & to distant sites (correlates in
general with their level of differentiation)
 contain central areas of necrosis
3. Local Invasion
 Benign neoplasms remain localized to their
site of origin.
 do not have the capacity to infiltrate,
invade, or metastasize to distant sites
4. Metastasis
 development of secondary implants
discontinuous with primary tumor
 more anaplastic & larger the primary tumor,
more likely is metastatic spread
 PATHWAYS OF SPREAD (metastasis):
 (1) Seeding within body cavities
(2) Lymphatic spread
(3) Hematogenous spread
(4) Local infiltration/invasion

FEATURE OF
MALIGNANT NEOPLASM
 Anaplasia (cellular atypia)
 Mitotic activity (abundant mitoses)
 Marked vascularity
 Invasive potential
 Metastasis – lymphatic / blood stream