Hypertrophy Hyperplasia Atrophy Metaplasia

1. ↑ size of cells & organ. - ↑ in NUMBER of cells Is adaptive and Mature differentiated
2. Occurs: where cells cannot - Restricted to cells capable of REVERSIBLE adult cell type is replaced
divide - Striated m. undergoing mitosis condition by another adult
3. No formation of new cells Skin epidermis: Squamous epi differentiated cell type.
(cell arrest) GIT: Columnar intestinal epi Results in a Etiology:
4. Physiologic: Increase in Glands: Cuboidal epi
muscle size with exercise.
decrease in cell Response to an adverse
Physiological hyperplasia
5. Cells become larger. size & organ environment
- Enlargement of uterus &
Cardiac & skeletal striated m. • REVERSIBLE
breast in pregnancy.
6. No cell swelling: • response to chronic
- ↑ protein in cellular irritation &
components inflammation
- no ↑ in cellular fluid
7. No ↑ in no. of cells!!!
1. PHYSIOLOGICAL PHYSIOLOGICAL - ↑ level of - Disuse atrophy: In i. Prolonged irritation in
i. Skeletal muscles (weight a normal stimulus paralysis & smokers: Pseudostratified
lifters, athletes) (hormonal) decrease workload. columnar bronchial
ii. Hormonal stimulation (i) In liver regeneration after - Degeneration epithelium - squamous
injury.
— Uterus smooth muscles atrophy (Multiple epithelium.
(ii) A compensatory response. Sclerosis)
during pregnancy – ii. Squamous epithelium
[Absence of organ in paired - Nerve
estrogen. organ or after partial resection] (lower esophagus) - gastric
2. PATHOLOGICAL denervation. columnar epi
iii. Wound healing: Scar tissue - Ischemic atrophy
i. Myocardial hypertrophy: formation. (HCl acid reflux – Barrett
Hypertension (kidney, heart) esophagus)
PATHOLOGICAL
- Pressure atrophy
Valvular stenosis Response to an excessive iii. Chronic infections -
- Malnutrition
stimulation. 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.
shape & (IUL) an adult
orientation of differentiated cell
epithelial cells with into
loss of another adult
differentiation. differentiated
* A STRONG
cell.
PRECURSOR OF
CANCER!!! Reversible
- asso. with chronic change
irritation or
inflammation ↓
Grossly: Not much can Aplastic organs are • Less severe Anaplastic cells:
be appreciated. either totally absent abnormality than i. Typically poorly
or represented by aplasia. differentiated or Dysplasia
Microscopically: small mass of • Rudimentary undifferentiated. Loss of cellular
i. Cellular atypia: fibrous or fatty organs are smaller ii. Exhibit cellular uniformity &
Cellular tissue containing a than normal. pleomorphism: tissue
pleomorphism & few rudimentary • Lack full - Variation in size architecture
hyperchromasia. cells. complement of cells, & shape of cells.
ii. Loss of so function may be
uniformity of reduced or ↓
individual cells compromised.
iii. Loss of Neoplasia
architectural New growth
orientation or
polarity. Irreversible
iv. Mitotic figures
may be seen.
Cervical dysplasia Paired organs – Unilateral renal
adrenals, kidneys, hypoplasia
lungs
 Coagulative Necrosis Liquefactive Necrosis Caseous Necrosis
• Seen in hypoxic or ischemic • Dominated by enzymatic digestion • found in foci of TB infection in
(infarction) death of all tissues of dead cells with total loss of association with Mycobacteria
except brain structural details • due to the presence of mycolic
• Denaturation of proteins is the • Seen in focal bacterial infections & acids within their cell membranes.
dominant process in some fungal infections • Appears cheese like on gross
• As enzymatic proteins get • Hypoxic death in BRAIN is examination
denatured → blocking of enzymatic always liquefactive • Microscopically shows
lysis • Cells are completely digested & fragmented cells with amorphous
• Affected tissue is firm & shows tissue becomes viscous liquid mass; granular pink appearance
preservation of basic outline of cell in abscesses, it becomes creamy
• Dead cells are removed later by yellow pus
phagocytosis or heterolysis
 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 is (2) Enzymatic antigens & antibodies are deposited
completely black in color & wood- ✓ Seen in acute in vessel wall
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 liquefactive m. & split triglyceride fibrinoid (– fibrinlike)
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:
Leukocyte Cellular Events
• 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)
1. Migration & Rolling
Chronic - Weeks to Months - Years
• Leukocytes settle out of central column,
Characterized by Hyperemia & exudation. marginating to vessel periphery.
MN’s - Lymphocytes & Macrophages • Tumble on endothelial surface, transiently
3 Major Components: sticking along the way
1. Alterations in vascular caliber → lead to a → rolling (pavementing)
local ↑ in blood flow (vasodilation). • Mediated by binding of complementary
2. Structural changes in the microvasculature → adhesion molecules on leukocytes &
permit plasma proteins to leave circulation. endothelial surfaces
3. Emigration of leukocytes from 2. Adhesion & transmigration b/w endothelial cells
microvasculature & accumulation in focus of • Leukocytes firmly adhere to endothelial
injury. 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.
Vascular Changes • Chemotactic agents – endogenous/ exogenous:
1. Changes in Vascular Flow & Caliber Soluble bacterial products, Complement
▪ Transient vasoconstriction of arterioles, system, products of Arachidonic Acid (AA)
followed by vasodilation. pathway metabolism & cytokines.
▪ Local ↑ in blood flow → redness (erythema) • They bind to specific receptors on leukocyte
& warmth. cell surface & stimulate the cell to move.
▪ Then, exudation of protein rich fluid into • They also induce leukocyte activation.
extravascular spaces. Phagocytosis
▪ ↑ blood viscosity, small b.v. are packed with 1. Recognition & attachment of particle to
RBCs → STASIS ingesting leukocyte
▪ Margination of leukocytes, followed by 2. Engulfment with subsequent formation of a
emigration. phagocytic vacuole
2. Increased Vascular Permeability (Vascular 3. Killing & degradation of ingested material
Leakage)
Defects in Leukocyte Function: Hematological Changes
• adhesion – bacterial infections • ↑ Erythrocyte sedimentation rate (ESR)
• chemotaxis / phagocytosis • Leukocytosis,
– Chediak Higashi syndrome • Anemia:
• microbicidal activity ✓ Blood loss in inflammatory exudate
– chronic granulomatous disease (ulcerative colitis)
✓ Hemolysis due to bacterial toxins
✓ Anemia of chronic disorders' due to
HARMFUL EFFECTS
toxic depression of the bone marrow
1. Digestion of Normal Tissues
o Lysosomal enzymes (collagenases &
proteases) digest normal tissues SUPPURATION
→destruction → vascular damage ✓ Formation of pus, a mixture of living, dying
2. Swelling and dead neutrophils & bacteria, cellular debris
o Acute epiglottitis in children due to and sometimes globules of lipid
Hemophilus influenzae, ✓ Once pus begins to accumulate in a tissue, it
o Acute meningitis → raise intracranial becomes surrounded by a 'pyogenic
pressure & ischemic damage membrane' consisting of sprouting
3. Inappropriate Inflammatory Response capillaries, neutrophils & fibroblasts.
✓ Forms an abscess, and bacteria within
BENEFICIAL EFFECTS abscess cavity are relatively inaccessible to
o Dilution of toxins, produced by bacteria, antibodies & to antibiotic drugs (acute
allows them to be carried away in lymphatics. osteomyelitis).
o Entry of antibodies. ↑ vascular permeability
allows antibodies to enter extravascular space. FATE OF ABSCESS
o Drug transport. Fluid carries drugs
✓ Abscess cavity collapses & is obliterated by
(antibiotics) to site of bacteria multiplying.
organization & fibrosis, leaving a small scar.
o Fibrin formation, from exuded fibrinogen
✓ Deep-seated abscesses sometimes discharge
may impede movement of micro-organisms,
their pus along a sinus tract (fistula).
trapping them & help phagocytosis.
o Delivery of nutrients & oxygen,
inflammatory cells which have high metabolic ULCERS
activity → ↑ fluid flow thru’ the area. ✓ local defect, or excavation, of surface of an
o Stimulation of immune response. The organ or tissue that is produced by sloughing
drainage of this fluid exudate into lymphatics (shedding) of inflamed necrotic tissue
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)
 CHRONIC INFLAMMATION
Features (Chronic vs Acute)
Chronic Acute
CHRONIC GRANULOMATOUS INFLAMMATION
- Sequence of continuing inflammation - vascular changes - Granuloma: a form of chronic inflammation
- Infiltration by mononuclear cells: - edema characterized by focal collection of activated
Macrophages - infiltration: neutrophilic macrophages & T lymphocytes due to
Lymphocytes infiltrate
Plasma cells persistence of a non-degradable / non-
- Tissue injury: Products of inflammation infectious agent accompanied by active cell
- Healing: Angiogenesis & fibrosis mediated hypersensitivity.
SYSTEMIC EFFECTS OF INFLAMMATION Granuloma Evolution Sequence

Activated T-Lymphocytes Release

Hallmarks of Chronic Inflammation

COMPOSITION

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

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 Pigmentation
1. Dystrophic Calcification Exogenous Pigments
Calcification in degenerated or dead necrotic tissue: 1. Carbon (Coal Dust) & Anthracosis
Hyalinized scars Pathog: On inhalation enters alveolar macrophages
Degenerated foci: Leiomyoma Transported to regional tracheobronchial LN
Tissue necrosis: Caseous & Fat Necrosis Blackening: Lung & affected LN
Microscopic cell injury: Chronic valvular heart disease Complic: i. Coal Miner’s lung or pneumoconiosis
PATHOGENESIS: ii. Lung fibrosis
• Activated phosphates bind Ca2+ ions to iii. Emphysema
phospholipids in cell membrane. 2. Tattoo
• Basophilic calcium salt deposits aggregate in Pathog: Intro of pigment into subQ tissue
mitochondria, progressively thru’out cell. Taken up by dermal macrophages
• Formation of calcium phosphates No inflammatory response
• Serum calcium: Not elevated
• Combination of fat & caseating necrosis
• Focal deposition of hydroxyapatite crystals in
Endogenous Pigments
previously damaged tissue 1. Lipofuscin (‘Wear & Tear’ pigment – insoluble)
Calcification in Dead Tissues: • 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)
MORPHOLOGY: • Derivative of tyrosine
• Present in melanocytes in epidermis
3. Hemosiderin
• Yellow-brown derived from hemoglobin
breakdown
• Stored iron in body cells coupled with
apoferritin
2. Metastatic Calcification Pathog: Excessive production: Hemorrhage
- Systemic mineral imbalance → elevation of Ca Hemosiderin granules in mononuclear cells
levels in blood & all tissues Does not impair cell function
ETIOLOGY: Diagnosis:
(i) Disturbances in calcium/phosphorus ➢ Prussian Blue Stain Reaction:
metabolism Colorless potassium
(ii) HYPERCALCEMIA: ➢ ferrocyanide-converted to blue-black ferric
✓ Persistently elevated Ca levels ferrocyanide
✓ Primary Hyperparathyroidism • Iron pigment: Coarse golden brown in
▪ ↑ parathormone secretion 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 Benign / Malignant Neoplasms
exceeds & is uncoordinated with that of normal
2 basic components:
tissues & persists in the same excessive manner
after cessation of stimuli which evoked the change. 1. proliferating neoplastic cells that constitute their
parenchyma.
• Progressive, Purposeless, Pathologic, Proliferation
2. supportive stroma made up of CT & b.v.
• Uncontrolled cell division
BIOLOGICAL FEATURES
Pathogenesis (Progressive DNA Damage!!!) 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
Exceptions: Leukemia, Lymphoma, Glioma, site of origin.
Hepatoma, Melanoma, Seminoma ✓ 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