INTRODUCTION TO PAnnnnnnnnnnnnnnnnnnnn THOLOGY.pptx

INTRODUCTION TO
PATHOLOGY
CAROLINE

INTRODUCTION
•The word pathology is derived from two Greek words-
pathos( meaning suffering) and logos (meaning study)
•Thus pathology is, thus, scientific study of changes in
the structure and function of the body in disease.
•In other words, pathology consists of the abnormalities
in normal anatomy ( including histology) and normal
physiology owing to disease

• Another commonly used term with reference to study of diseases is
pathophysiology ( pathos – suffering, physiology – study of normal
function).
• Pathophysiology, thus, includes study of disordered function(i.e.
physiological changes) and breakdown of homeostasis in diseases(i.e.
biochemical changes).

DEFINITION OF PATHOPHYSIOLOGY
• The study of the essential nature of diseases, disease processes, and
the structural and functional changes in organ and tissues that cause or
are caused by diseases.
• The study of the gross and microscopic pattern of disease.

TERMINOLOGY
• Patient is the person affected by the diseases
• Lesions are the characteristic changes in tissues and cells produced by
disease in an individual or experimental animal.
• To understand pathology four aspects of diseases must be known:
• A. Etiology: causing factors responsible for disease
• B. Pathogenesis: the mechanism of how the disease develops
• C. Morphologic changes: which includes both gross (macroscopic)
and microscopic alterations induced in the cells and organs of the
body.

• D. clinical significance: the functional consequences of the above
morphologic changes by which the patient presents to the doctor.

ETIOLOGY
• 2 major classes of etiologic agents or factors
• (1) intrinsic, inherited or genetic
- age
- gene

• (2) acquired or environmental factors
- physical - infections - psychological
- chemical
- nutrition - immunological
• (3) Idiopathic : where the exact cause is not known

PATHOGENESIS
• The mechanism by which the characteristic changes are made in the
tissue and cells.
• It refers to the sequence of events that occur to the stimulus by the
etiologic agent, from the initial response to complete expression of the
disease.
• There are various changes occur at different levels.
• For example biochemical, immunologic, genetic and morphologic
events.

MORPHOLOGY
• The changes can be recognized by the naked eye are gross or
macroscopic changes
• Those that have been studied at the cellular levels done by use of
microscopes are microscopic changes

CLINICAL SIGNIFICANCE
• The various morphologic changes affecting different tissue and their
distribution in different systems determine the influence on functional
abnormality and reflects the clinical outcome in the form of signs and
symptoms, cause and prognosis of the disease.

MEDICAL PATHOLOGY
• It is divided into two parts
• 1. General pathology – is a broad and complex scientific field which
seeks to understand the mechanism of injury to cells and tissues as
well as the body’s means of responding to and repairing injury.
• Areas of study include cellular adaptation to injury, necrosis,
inflammation, wound healing and neoplasia
• Eg: common inflammation, cancer, ageing

• Systemic pathology: specific changes in organs.
• Eg: goiter, pneumonia, breast cancer

CLINICAL PATHOLOGY
• It is a medical specialty that is concerned with diagnosis of disease
based on laboratory analysis of bodily fluids such as blood and urine,
using tools of chemistry, microbiology, hematology and molecular
pathology.
• This is divided into different subspecialities.

• HISTOPATHOLOGY:
• Is the classic method to study the morbid anatomy, the gross changes of
tissues obtained from the body b y various procedures.
• Eg: tru cut biopsy, needle biopsy, excision biopsy is done as major and
minor procedure
• Further divided as cardiac pathology, neuropathology, renal pathology,
dermatopathology, oral pathology etc

• CYTOPATHOLOGY
• It includes study of cells shed off from the lesions (exfoliative cytology)
and fine needle aspiration cytology from superficial and deep seated
lesions.
• CLINICAL PATHOLOGY
• This includes the study of various body fluids
• Eg: urine, seminal fluid, synovial fluid
• HAEMATOLOGY
• Sub speciality that deals with diseases of blood. It includes laboratory
haematology-haemogram, ESR, hematocrit, cell counts of RBCs, WBCs,
platelet count, bone marrow study etc.

• MOLECULAR PATHOLOGY
• The detection/diagnosis of abnormalities at the molecular levels-DNA
level, Micro-array, Nanotechnology technique etc.
• GENETIC PATHOLOGY
• Cytogenetics is the study of medical genetics, genes and their
abnormalities in various disease process- chromosomal aberrations in
inborn errors of metabolism etc.

IMPORTANCE OF PATHOLOGY
• General knowledge of how disease are caused
• General patterns and classification of diseases
• Evolution of disease from its causes to clinical presentation
• The signs and symptoms of disease
• Nature, spread and precautions to prevent common diseases
• Know the different disciplines that make up pathology
• Better understand the patient and his diseases

IMPORTANCE OF PATHOLOGY IN
NURSING
• Nurses today are not merely restricted to providing bedside care to
sick and injures hospitalized patients; they have more challenging
expansions and extensions of their role in health care delivery system.
• The study of pathology will prepare the nurses to understand how the
disease started, what was the main cause of disease process, how
diseases are diagnosed and what changes may be expected at cellular,
tissue and organ level during the illness.

• The significance of studying pathology as a separate subject by nurses
is discussed below:
• 1. understanding the causes of diseases: the knowledge of pathology
will equip the nurses with following essential information related to
etiology and pathogenesis of diseases:
- to understand the pattern and classification of disease
- understanding the basic nature of diseases such as inflammatory,
degenerative, hemodynamic, infective, autoimmune and neoplastic
- to understand the etiology and pathophysiological mechanisms,
which underlie a disease process
- to familiarize the nurses with various diagnostic tests and
the terminologies used in pathological repots.

• 2. knowledge about the progression of disease: the knowledge of
pathology help the nurses to understand the basic structural and
functional changes that occur in tissues, organs and body as a whole.
Furthermore, knowledge of pathology helps the nurses:
- to understand the morphological changes, which may take place in
the body during various disease processes.
- to appraise the evolution of disease from its causes to the clinical
presentation including signs and symptom of disease
- to correlate the clinical features with the structural and functional
pathological alterations in the organs due to disease process
- serves as a foundation for nurses to understand the pathophysiology
of a disease, so that nursing care can be planned more efficiently

• 3. Early and effective diagnosis of disorders: The clinical
manifestations of several diseases may be similar, but the treatment of
these conditions may vary considerably. There are numerous
pathological tests available and the health care provider needs to have a
sound knowledge of pathology so as to order the most relevant test.
• 4. Prevention of diseases: There are several routine screening tests
which assist the health care providers to diagnose a disease in the initial
stages and therefore take the preventive measures. For example FNAC
for breast lumps
• 5. Helps in effective management and care of patients: helps the nurses
to understand the ongoing health status of patient and to assess whether
the patient is responding to treatment, by monitoring a series of
pathological lab results.

CELL INJURY
• Normally a cell can handle its normal physiologic demands and
maintain a steady state called homeostasis.
• It usually occurs when the cells are subjected to severe stress that they
are no longer able to adapt.
• There are two phases in cell injury
- initial reversible phase
- final irreversible phase

ETIOLOGY
• Can be reversible or irreversible
• Broadly classified into two groups
- inherited/ genetic causes
- acquired causes

• GENITIC CAUSES:
- Normally human germ cells contain 23 chromosomes ( ova and
sperm)
- Females 46 XX and males 46 XY
• Occur due to abnormalities of the chromosomes
• 2 types
1. numerical abnormalities
2. structural abnormalities

• Numerical abnormalities of chromosomes:
a) polyploidy - more than two set of chromosomes
- 69 (3N) 0r 92 (4N) chromosomes
b) aneuploidy – occurrence of one or more extra or missing
chromosomes
45 chromosomes monosomy, 47 chromosomes trisomy
Important clinical syndromes
syndrome, Turner’s syndrome
• Structural abnormalities:
– Down’s syndrome, Klinefelter's
• During cell division certain structural abnormalities may appear
• Eg: translocations, deletions, inversions, ring chromosome and
isochromosome

• Clinical syndromes: chronic myeloid leukaemia (translocation),
retinoblastoma ( deletions)
• ACQUIRED CAUSES:
• Hypoxia and ischemia:
- can result from
- decreased blood supply
- anaemia, carbon monoxide poisoning, cardio respiratory
insufficiency etc.
• Physical agents:
- may be due to
- mechanical trauma – accidents
- thermal trauma – by extreme heat or cold temperatures
- electricity
- radiation

• Chemical agents:
- poisons - cyanide, arsenic
- strong acids or alkalis
- environmental pollutants
- insecticides and pesticides
- high concentration of oxygen
- hypertonic glucose and salt
- alcohol and narcotic drugs
- therapeutic drugs

• Microbial agents:
- bacteria, rickettsiae, viruses, fungi, protozoa, metazoan and other
parasites
• Immunologic agents:
- double edged sword – protects the host against various harmful
agents and at the same time can become lethal and cause cell injury.
Eg: hypersensitivity reactions
• Nutritional derangements:
Any imbalance in the nutrients due to either excess or deficiency causes
nutritional derangement.

• Psychological factors:
- psychosomatic factors – mental stress, anxiety, overwork, frustration-
all result in acquired mental disorder
Eg: depression, schizophrenia

PATHOGENISIS OF CELL INJURY
• Few of the general principles associated with pathogenesis by most
forms of etiologic factors are as follows
• Type, duration and intensity of the injurious agent
• Type status and adaptability of the target cells
• Morphologic changes
• Underlying intracellular biochemical alterations

• In any type of cell injury, there are few main cellular structures that are
usually targeted
• Aerobic respiratory mechanism
• Integrity of the cell membrane
• Protein synthesis
• Cytoskeleton
• Generic apparatus

• Major biochemical mechanisms that involved in the cell inury include
• 1. depletion of adenosine triphosphate
• 2. alteration in energy metabolism of cell
• 3. damage to cell membrane
• 4. failure to calcium homeostasis
• 5. mitochondrial damage

Depletion of adenosine triphosphate
• Occurs in hypoxic and chemical injury
• NormallyATP is required for energy dependent functions such as
- membrane transport
- protein synthesis
- lipogenesis

• Depletion leads to defective functioning of the Na/K dependent energy
pump which causes excessive loss of potassium from the cell and high
influx of sodium into the cell, whenever a molecule of sodium moves
into the cell it carries a molecule of water.
• Swelling of the cell and loss of specialized structures like the microvilli
and brush border.

Alterations in Energy Metabolism of Cell
• As a result of the lack of energy molecules from the oxidative
pathway, the cell tries to derive energy from other pathways.
• The most common pathway is glycolytic pathway.
• The glycogen breaks into lactic acid and pyruvic acid and in this
process it liberatesATP which is used by the cell.
• This pathway is called anaerobic pathway.
•

• This leads to rapid depletion of glycogen stores producing moth eaten
appearance of the cytoplasm with accumulation of lactic acid and
pyruvic acid.
• Accumulation of the acids lead to fall in the cytoplasmic pH and as a
result of this the functioning of various cytoplasmic enzymes is affected
and there is decrease in the protein synthesis.

•Damage to Cell Membrane
•Damage to the cell membrane is a major event in the
cellular injury. The damage is induced by various
mediators of cell injury, such as free oxygen radicals,
rise in the cytosolic calcium levels and others. Cell
membrane damage leads to the following:
•Loss of osmotic balance of the cell
•Influx of water and ions into the cell
•Loss of proteins, enzymes, coenzymes, and metabolites

• Depletion of high energy phosphates
• Damage to the mitochondrial cell membrane leads to severe
mitochondrial dysfunction
• Damage to the lysosomal membrane leads to leak of the lysosomal
enzymes and activation which causes digestion of the cellular
components

MITOCHONDRIAL DAMAGE
• Mitochondrial damage occurs due to increased systolic calcium,
oxidative stress, increased breakdown of phospholipids and break
down of lipids
• Leads to alteration in the mitochondrial membrane permeability and
thereby defective oxidative phosphorylation. There is release of
cytochrome C into the cytoplasm which triggers the death of the cell.

Failure of calcium homeostasis
• Normally calcium is kept in a very low level within the cytoplasm
within the endoplasmic reticulum and the mitochondria.
• Due to ischemia and certain toxins, the calcium is released from the
organelles and intracellular calcium level is elevated. This leads to
activation of various enzyme systems, such as ATPase, phospholipase,
protease, and endonuclease. The elevated calcium levels also increases
the membrane permeability of mitochondria.

Mediators of cell injury
• The common mediators include the free oxygen radicals and
cytosolic calcium.

Free oxygen radicals
• These are reactive oxygen molecules which have an unpaired
electron in its outermost orbit.
• They are extremely reactive and capable of undergoing chain
reactions with the generation of more free oxygen radicals.
• They are usually represented as O2

• They mediate various forms of cell injury mostly due to radiation,
chemical, and ischemia/reperfusion.
• They also play a vital role in mediating the cellular damage due to
ageing and aid in microbial killing by the phagocytes.
• The common free radicals include O2, HO2, OH, and NO.
• The free radicals
-Lipid peroxidation of the cell membranes- cell membrane
damage
- Protein breakdown
- damage to DNA
causes

• Usually action of these balanced by substances which are normally
present in our body called antioxidants. They inactivate the free
radicals and terminate the damage induced by radicals.
• Common antioxidants include catalase superoxide dismutase,
glutathione peroxidase, transferrin, ferritin, lactoferrin, vitamins E, and
A.

Ultrastructural changes of reversible cell injury.
• a) Distension of endoplasmic reticulum
• b) Mitochondrial swelling.
• e) Loss of microvilli & presence of focal projections of cytoplasm
(blebs).
• d) Chromatin material becomes clumped and fibrillar and granular
component of nucleus becomes segregated.
• e) Visible light microscopic changes are cell swelling (hydropic
swelling) and fatty change.

Morphological Patterns of Reversible Cell
Injury
• They include:
• Cellular swelling-hydropic/vacuole degeneration
• Fatty change
• Hyaline and mucoid change

Cellular Swelling
• It is the most common morphological form of cell injury. This occurs
due to the loss of maintenance of the fluid and ionic balance as a result
of the defective functioning of the Na/K-dependent pump.
• This is manifested well in renal tissue and the change is called cloudy
swelling of the renal tubules. The organ looks paler with increased
turgor and weight. On light microscopy, the cells are swollen with
small vacuoles within the cytoplasm and increased granularity of the
cytoplasm

• This leads to irregularity of the tubular lumina which is
referred to as starry lumina
• Electron microscopy shows widespread alterations in the
plasma membrane, mitochondria, endoplasmic reticulum and
nuclear chromatin

Fatty change
• Cell accumulates an intracellular substance in excessive manner.
• Lipid accumulation is the most common form and the cell accumulates
triglycerides, cholesterol, phospholipids and esters of cholesterol
• Can occur in liver, heart, muscle and kidneys
• Most common site – liver- site of lipid metabolism

Causes of Fatty Change Liver
• Chronic alcoholism (most common)
• Toxins-carbon tetrachloride
• Protein calorie malnutrition
• Diabetes mellitus
• Obesity
• Anoxia
• Infections-hepatitis C virus
• Late pregnancy
• Reye's syndrome
• Drugs- estrogen, corticosteroids, tetracycline

• Gross: The liver is enlarged, yellowish, and greasy. The edges of the
liver are blunt
• Microscopy: The hepatocytes are swollen with accumulation of micro
vesicles of fat which gradually fill the entire cell.
• The fat usually appears as clear spaces within the cytoplasm, because
the fat is dissolved in the chemicals used for tissue processing in the
laboratory.
• This pattern of staining is called negative staining.
• Fat can be demonstrated using special stains, such as Sudan Black B,
Sudan III, Sudan IV, and Oil red O in a frozen section.

Hyaline and mucoid change
• Hyaline is used to describe glassy, homogenous eosinophilic
appearance of material in routine
• Can be intracellular or extracellular
• Intracellular hyaline accumulations is seen in epithelial cells.
• Eg: hyaline droplets in proximal tubules
• Mallory hyaline bodies seen hepatocytes due to alcohol injury

• Extra cellular Hyaline: This change is seen in the connective tissue
stroma & is little difficult to analyze.
• Eg: 1. Old Fibrous Scar:Appear hyalinized.
• 2. Long standing hypertension & Diabetes mellitus-arteriosclerosis
is seen in kidney.
• Hyaline change has to be differentiated from fibrin and amyloid which
look almost similar but have subtle distinctive features & staining
reaction.

• Mucin is normally produced by epithelial cells of mucous membranes
and mucous glands, as well as by some connective tissues like in the
umbilical cord. Mucin of connective tissue are produced often when
disturbed.
• Eg: cystic fibrosis

When does the Cell Actually Die?
• Unable to reverse the mitochondrial dysfunction as well as cellular
damage

• IRREVERSIBLE CELL INJURY:
• If the acute stress to which a cell must react exceeds its ability to adapt
the resulting changes in structure and function lead to the death of the
cell. Common causes of cell death are viruses, ischemia, physical
agents such as ionizing radiation, extremes of temperatures or toxic
chemicals. 2 types of cell death are known.
• Necrosis - It is a Consequence of catastrophic injury to cell integrity
• Apoptosis-Programmed cell death.
• The exact point of no return and the exact molecular mechanism
connecting cell injury to cell death is not clear.

• Important changes of irreversible cell injury are:
• a) Mitochondrial dysfunction : Seen as vacuoles and amorphous
calcium salt deposits in mitochondrial matrix, seen ultra structurally
by electron microscope.
• b) Membrane damage: Resulting in dysfunction of membrane.
Lysosomal membranes are damaged causing a leak of lysosomes into
an already lowered pH (due to ischaemia) and these enzymes degrade
cytoplasmic and nuclear components. This pattern is the cause for
necrosis. Apart from this, there is excessive leak of intracellular
substances into the adjacent tissue and into circulation. These enzymes
released into the circulation are used as markers for tissue damage. eg.
SGOT (serum glutamic oxaloacetic transaminase, LDH (lactic
dehydrogenase) cardiac troponins.

MORPHOLOGY OF IRREVERSIBLE CELL
INJURY (CELL DEATH)
• The two major morphological forms of cell death include
- necrosis
- apoptosis

NECROSIS
• Definition:
• The spectrum of morphological changes that follow cell death in a
living tissue. This is mostly induced by the proteolytic degradative
action of the enzymes on the injured cell. The enzymes may be
released from the same cell (autolysis) of from the adjacent cells and
inflammatory cells (heterolysis).
The two major events that occur in necrosis are:
• 1. Denaturation of the cellular proteins
• 2. Enzymatic digestion of cells

Morphology of a necrotic cell
Cytoplasmic changes:
• Increased eosinophilia of the cytoplasm due to denaturation of protiens
• Classy and moth eaten appearance of cytoplasm due to loss of
glycogen
• Presence of calcification
Nuclear changes
• Small shrunken nuclei with condensed chromatin – pyknosis
• Dissolution of the nuclei(due to the acidity of DNAse) – karyolysis
• Fragmentation of the pyknotic nuclei - karyorrhexis

• Ultrastructural changes
• Cell membrane and plasma membrane damage
• Mitochondrial alterations
• Presence of amorphous densities in the mitochondria
• Lysosomal membrane alterations
• Aggregation of denatured proteins

Types of necrosis
• Coagulative necrosis
• Liquefactive necrosis
• Caseation necrosis
• Fat necrosis
• Gangrenous necrosis
• Fibrinoid necrosis
• Osteonecrosis
• Zenker’s degeneration

Coagulative Necrosis (Structured Necrosis)
• Causes: Ischemia and hypoxia.
• Organs involved: Heart, kidney, spleen
• Morphology
• Gross :initial changes: pale, firm and slightly swollen
later – yellowish, softer and shrunken

• Microscopically: cells like “tombstones” i.e., only outline of
the cells are preserved, so that the cell type can still be are
recognized, where as the cytoplasm nuclear details are lost.
• the nucleus may either be pyknotic, or undergo karyorrhexis
& karyolysis and ultimately the nucleus disappear.
• Inflammatory response is elicited in the surrounding tissue and
the dead cells are phagocytosed leaving behind granular debris
& fragments of cells.

Liquefactive Necrosis
• Causes: ischemia, bacterial infections
• Organs involved : brain, kidney, skin
• Major event: enzymatic digestion
• Morphology
• Gross changes: are soft with necrotic centre. Later cyst wall is formed
surrounding area
• Microscopically: lesion consist of necrotic cell debris, macrophages
filled with phagocytosed material. The cyst wall is formed by
proliferating capillaries, fibroblasts and inflammatory cells.

Caseation Necrosis
• Caseous Necrosis: This type of necrosis has a combination of
coagulative necrosis and liquefactive necrosis and is characteristic of
tuberculous infection.
• Caseous means cheesy white, thought to be due to potent histotoxic
effects of lipopolysaccharides present in the capsule of the tubercle
bacilli - Mycobacterium tuberculosis.
• Necrotic cells do not retain the cell outlines nor do they disappear
completely, instead form a coarsely granular material.

• Gross: dry cheese, is soft, granular and yellowish hence the name
caseous necrosis.
• Microscopically-The necrotic areas appear as eosinophilic amorphous
granular debris.
• Epithelioid cells ( activated macrophages) – pale pink cytoplasm, cell
boarders not distinct.
• Nucleus is pale, oval to elongate with slight folding – slipper sole
appearance
• Epithelioid cells fuse to form gaint cells – two types
• Langhan’s type – nuclei arranged in periphery – horse shoe appearance
• Foreign body type – nuclei are haphazardly arranged

Fat Necrosis:
• It is a special form of cell injury which occurs in adipose tissue and most
commonly results from pancreatitis and trauma.
• eg.Acute pancreatic necrosis.
• Traumatic fat necrosis of breast tissue.
• Pathogenesis: When digestive enzymes get released from injured
pancreatic acinar cells into the extracellular spaces & get activated, they
digest the pancreas itself and the surrounding tissues, including adipose
cells/ fat cells.
• Then triglycerides get released from adipocytes and the pancreatic
lipases act on them to form free fatty acids.

• These fatty acids are precipitated as calcium (saponification) which is
soaps seen microscopically as amorphous basophilic deposits of the
necrotic adipocytes.
• Gross: The lesion appears as yellowish white firm deposits,
saponification makes the area firm and appear as chalky white,
embedded in otherwise normal adipose tissue.
• Microscopically: Necrosis appears as a foci of shadowy outlines of
necrotic fat cells with amorphous granular basophilic calcium
deposits, and surrounded by an inflammatory reaction.

Fibrinoid Necrosis:
• Fibrinoid necrosis or fibrinoid degeneration is characterized by
deposition of fibrin-like material usually in an injured vessel wall.
• It is usually seen in immunologic injury (eg: in autoimmune disease,
immune complex vasculitis), arterioles hypertension, etc.
• Microscopically: Fibrinoid necrosis is identified by intensely
eosinophilic, hyaline -like deposition in the vessel wall, usually
associated with rupture of the blood vessel

Osteonecrosis
• Causes: ischemia, radiation, traumatic
• Organs: head of femur, navicular bone
• Major event: protein denaturation

Zenker’s degeneration
• Causes: enteric fever
• Organ: rectus abdominus, diaphragm
• Major event: protein degeneration
• Features: muscle fibers loose the striations and appear as eosinophilic
hyaline masses

Gangrene
• Definition: It is a type of coagulative necrosis with
superadded putrefaction.
• Cause: Due to ischemia with superadded severe bacterial infection.
Types
• Three major types
• 1. Dry gangrene
• 2. Wet gangrene
• 3. Gas gangrene

• DRY GANGRENE:
• Example: Gangrene of distal part of lower limbs in the old, is usually
due to arteriosclerosis.
• Other eg: Buerger's disease (thromboangiitis obliterons TAO) Raynaud's
disease, trauma etc.
• It begins in the part, distal to the obstruction of the blood supply. Initially
the invading bacteria find the hypoxic condition difficult to grow in the
necrosed areas. The gangrene, later slowly spreads forwards to reach
area of adequate blood supply. There is a fine line of demarcation
between the gangrenous part and the viable part.

• Morpologic changes:
• Gross: The affected part appears dry, shrunken, dark black similar to
'mummy' (mummified). The bacterial hydrogen sulphide (H,S) act upon
the haemoglobin released from the hemolyzed red blood

APOPTOSIS (PROGRAMMED CELL
DEATH):
• Apoptosis is a pathway of cell death. It refers to a genetically
determined internal, self destruction mechanism of cell death, which
gets activated under a variety of circumstances.
• Apoptosis is a Greek word meaning 'falling off' or 'dropping
off“(1972).
• Normally unwanted (or) potentially harmful cells and cells that have
outlived their usefulness get eliminated by apoptosis. It also plays a
role in elimination of irreparably damaged cells by pathologic events.

Apoptosis as physiologic processes:
• 1. Organized cell death during embryogenesis right from implantation of
embryo to the metamorphosis into fetus and the newbom.
• 2. Involution of cells in hormone-dependent tissues eg: In breast-during
lactation and after weaning, endometrial shedding in menstrual cycle,
atresia of ovary after menopause etc.
• 3.Involution of thymus in young age.
• 4.Cell destruction in normally proliferating and replacing cell
populations, so as to maintain a constant number eg. in intestines.

Apoptosis in pathologic conditions.
• 1. Cell death produced by numerous injurious stimuli such as
radiotherapy & chemotherapy in cancer patients, cause damage to
DNAof cells.
• 2. Viral infections like hepatitis, result in council man bodies - which
are apoptotic bodies.
• 3.Atrophy of organs/tissue beyond the point of obstruction -
pancreas, parotid gland.
• 4. Degenerative diseases of CNS Alzheimer's disease, Parkinsonism
etc.

• Morphologic changes:
• Cell shrinkage: The cell becomes small with dense cytoplasm and
tightly packed cytoplasmic organelles. It becomes rounded and looses its
specialized structures like the microvilli.
• Condensation of chromatin: with the aggregation of the chromatin
under the nuclear membrane.
• Formation of cytoplasmic blebs: Extensive surface blebbing with
fragmentation. Phagocytosis of the apoptotic bodies by the macrophages
due to surface expression of vitronectin, beta 3 integrin, thrombospondin
by the apoptotic cells.

• These apoptotic cells can be identified and counted by the following
methods.
• a) Nuclear chromatin staining by hematoxylin, Feulgen or acridine
orange.
• b) Flow cytometry show cell shrinkage.
• c) DNAchanges detected by in situ techniques
• d)Annexin V as apoptotic cell membrane marker.

Mechanism:
• It occurs in two phases- initiation and execution.
• 1. Initiation: Initiation can occur by two pathways:
• (1) Intrinsic pathway: is mediated by the mitochondria and
• (2) Extrinsic pathways mediated by the death receptors.
• (i) Intrinsic pathway: Due to the damage to the mitochondrial
membrane, there will be release of proapoptotic signals from the
mitochondria,
• e.g., BAK, BAX, BIM, and cytochrome C.
• The mitochondria also contains antiapoptotic molecules, such as bcl-2
and bcl-x. Due to stress, these molecules are lost and are replaced by
the proapoptotic proteins which can also initiate the process of
apoptosis.

• (ii) Extrinsic pathway: This pathway is mediated by extracellular
signals.
• Many cells express death receptors on its surface.
• They belong to the tumor necrosis factor (TNF) family.
• When this receptor is activated by a related protein called Fas (CD95),
it leads to the activation of an adapter protein called Fas associated
death domain (FADD) which in turn activates the enzymes of the
execution phase and kills the cell.
• 2. Execution: It is mediated by enzymes of the caspase family,
namely, transglutaminase and endonuclease. Transglutaminase causes
cleavage of proteins and endonuclease causes chromatin condensation
and DNAfragmentation.

• Removal of dead cells:
• Dying cells secrete certain soluble factors which recruit phagocytes in
facilitating prompt phagocytosis and thereby clearing apoptotic cells,
before they undergo necrosis
• It is too rapid process, hence no inflammatory reaction is ever seen and
the dead cells disappear without leaving any sign.

GANGRENE
• Is a form of tissue necrosis with superadded invasion by putrefactive
organisms.
• It is usually coagulative type of necrosis due to ischemia
• Eg: gangrene of intestine, limb etc

TYPES OF GANGRENE
• 3 types
Dry gangrene
Wet gangrene
Gas gangrene
In all these types coagulative necrosis undergoes liquefactive change
by the superadded microorganisms.

DRY GANGRENE
• Eg: gangrene of distal part of lower limbs in the old, is usually due to
arteriosclerosis. Other example Burger’s disease (thromboangitis
obliterans, TAO) Raynaud’s disease, trauma etc.
• It begins in the part, distal to the obstruction of the blood supply.
• Initially the invading bacteria find the hypoxic condition difficult to
grow in the necrosed areas.
• The gangrene, later slowly spreads forwards to reach area of adequate
blood supply.

• There is a fine line of demarcation between the gangrenous part and the
viable part.
Morphologic changes:
• Gross: the affected part appears dry, shrunken, dark black similar to’
mummy’
• The bacterial hydrogen sulphide act upon the haemoglobin released
from the haemolyzed RBC to form iron sulphide which imparts black
colour to the affected part
• If the affected part not removed surgically, there
would be complete separation and eventually the
gangrenous part falls off.

• Microscopically : Necrosis with ill defined smudgy tissue is seen.
However the line of separation consists of inflammatory cells admixed
with granulation tissue.

• WET GANGRENE:
• This type of gangrene occurs in moist areas/tissue/ organs for eg: mouth,
lung, cervix, bowel etc.
• Also seen in diabetic patients with high blood sugar content in the
affected area, promoting bacterial growth.
• Bed sores are the other important site for wet gangrene.

• The mechanism here is often due to thrombosis (or) embolism of the
venous blood flow, thereby causing the affected part to get stuffed with
blood which favors rapid growth of putrefactive bacteria.
• The toxic products thus released by the bacteria get absorbed into the
circulation resulting in septicemia which may finally lead to death.
• Does not have a line of demarcation and may spread without any limit.

• Morphologic changes :
• Gross: The affected part is soft, swollen, rotten, dark and emits rotten/foul
smell.
• Microscopically: eg: Gangrene of Intestine due to volvulus,
intussusception etc.
• Mucosa is ulcerated with loss of lining epithelium, congested with blood
and the lumen contains blood & mucus clot with intense inflammatory
cell infiltration in all the layers of the intestine.

• GAS GANGRENE:
• It is a distinctive and special form of wet gangrene caused by gas
forming anaerobic organisms which are gram positive and belong to the
species clostridium.
• These bacteria enter the tissues through open contaminated wounds, and
cause cellulitis and muscle necrosis of traumatic surgical wounds.
• Eg: Uterine myonecrosis in illegal abortions; clostridia produce various
toxins most important is the alpha toxin which cause necrosis and edema
locally and if absorbed systemically lead to life threatening septicaemia.

• Morphologic Changes:
• Gross: The affected area is swollen, edematous crepitant due to bubble
of gas getting accumulated within the tissues seen within 1 to 3 days
after injury. Later the tissue becomes dark, black and foul smelling
with fluid exudating after rupture of vesicles.
• Microscopically: The tissues
liquefaction. Plenty of gram
undergo coagulative necrosis with
positive bacilli can be identified
surrounding area consists of leucocytes, edema and congestion &
haemorrhage. Capillary & venous thrombi are commonly present.

CELL ADAPTATION
• In response to persistent stress, a cell dies or adapts.

•Hyperplasia
• Definition: It is defined as increased volume of the organ due to
increase in the number of cells in an organ/tissue. It occurs only in
organs with dividing cells.
• Types: There are two types of hyperplasia- physiological and
pathological:
• 1. Physiologic hyperplasia may be induced by hormones, e.g., (1)
increase in the size of female breast during puberty/ pregnancy, (2)
increase in the size of uterus during pregnancy, or hyperplasia may also
occur as a compensatory process, e.g., regeneration of liver following
hepatectomy.

• 2. Pathologic hyperplasia usually occurs due to excessive hormonal
stimulation, e.g., (i) estrogen-induced hyperplasia of the endometrial
tissue, (ii) hormone-induced hyperplasia of prostate.
• These hormone-induced pathologic hyperplasias constitute a fertile
soil for cancerous growth.

Hypertrophy
• Definition: It is defined as increase in the size of the organ due to increase in
the size of the cells.
• In contrast to hyperplasia, there are new cells but the existing cells become
larges
• Hypertrophy usually occurs in nondividing cells. There are two forms-
physiologic and pathologic
• 1. Physiologic hypertrophy, e.g., hypertrophy of the muscles due to exercise;
hypertrophy of uterus in pregnancy.
• 2. Pathologic hypertrophy, e.g., hyper trophy of the cardiac chambers due to
hemodynamic overload as in hypertension and valvular heart diseases.
• The basic molecular mechanism for hypertrophy is due to the synthesis of
newer cellular proteins or excessive secretion of growth factors.

Atrophy
• Definition: It is defined as reduction in the size of the organ and due to
decrease in the size of the cell.
• An atrophic cell has diminished function but it is not dead.
• Atrophy can be physiological or pathological.
• Physiologic atrophy usually occurs during
-Embryogenesis, e.g., atrophy of the thyroglossal duct or notochord
-Adult life, e.g., atrophy of thymus, gonads, skin due to aging.
• Pathologic atrophy is due to
- decreased workload (disuse atrophy) eg: limbs immobilized in plastic
cast

- loss of nerve supply (denervation atrophy) eg: muscle wasting
- loss of blood supply – changes in brain due to ischemia
- inadequate nutrition – protein energy malnutrition, cancer
- loss of endocrine stimuli – atrophy of uterus, ovaries
- aging – senile
- pressure – tissue compressed for a longer duration
The major molecular mechanism of atrophy is due to excessive
degradation of structural proteins or an imbalance between the protein
synthesis and degradation.

Metaplasia
It is defines as a reversible change of one adult type tissue into another.
There are two type of metaplasia
- epithelial and mesenchymal
Epithelial metaplasia
• Change of columnar epithelium to squamous epithelium
• Eg: - respiratory tract – chronic irritation, smoking
- ducts of salivary gland, pancreas – calculi
- urinary bladder – deficiency of vitaminA

• Change of squamous to columnar epithelium,
• e.g.,Lower end of esophagus (Barrett's esophagus)-reflux of gastric acid
Mesenchymal Metaplasia
• Myositis ossificans: It is condition of formation of bone within a muscle
tissue induced by trauma.
• The major underlying molecular mechanism of metaplasia is genetic
reprogramming of the precursor stem cells. The metaplastic cell will be
able to withstand the stress better than the original cell. Metaplastic
tissue can also be fertile soil for cancerous change.

Dysplasia :
• Refers to an alteration in the size, shape and organization of the cellular
components of a tissue.
• Dysplasia is often associated with hyperplasia and metaplasia, hence
also called as hyperplasia
• Occurs in epithelial cells
• Types
• Based on the depth of dysplastic cells, it is divided into mild, moderate
and severe

• Mild dysplasia : grade – I when 1/3rd or less of epithelium thickness
shows dysplasia
• Moderate: grade – II when 1/3rd to 2/3rd thickness shows dysplasia
• Severe: grade – III when more than 2/3rd but not full thickness
Dysplasia occurs due to chronic irritation or prolonged inflammation.
Once the stimulus is removed changes may disappear or may progress to
severe form to be called carcinoma in situ.
• carcinoma in situ: when dysplasia is seen in full thickness of epithelium,
but the basement membrane is still intact.

MEANING
• Is the complex reaction of a tissue and its micro-circulation to a
pathogenic insult.
• An expression of the host attempt to localise and eliminate
metabolically altered cells, and the agent causing it.
Agents
1. Infective agent – bacteria, fungi, viruses and their toxins.
2. Physical agent – heat, cold, radiation, mechanical trauma
3. Chemical agent – drugs, organic and inorganic poisons

• 4. Immunologic agents – antigen-antibody reactions, all
hypersensitivity reactions
Signs of inflammation
In 2nd centuryAD, the Roman encyclopaedistAulus Celsius described
the four cardinal signs of inflammation
1. Rubor (redness)
2. Calor (heat)
3. Tumor (swelling)
4. Dolor (pain)
Rudolf Virchow later added 5th sign – function laeso – loss of function

• Types of inflammation
• Depending upon the duration of host response, persistence of injury,
nature of inflammatory response and clinical symptoms
- acute
- chronic
• Acute inflammation: is rapid in onset (seconds or minutes) and short
duration lasting for few minutes, hours or to few days, associated with
acute inflammatory cells- polymorphs and is usually followed by repair.
• Chronic inflammation: longer duration and occurs when the causative
agent of acute inflammation persists for a long time with presence of
chronic inflammatory cells- lymphocytes- plasma cells and
macrophages

ACUTE INFLAMMATION:
• The changes in acute inflammation are described under two headings:
• I. Vascular reaction (or) vascular events.
• II. Cellular reaction (or) cellular events.
I. Vascular events:
• Alteration in the micro vasculatures (venules, capillaries and
arterioles) is the earliest response to tissue injury.
• The alterations are:
• a) Haemodynamic changes
• b)Altered vascular permeability.

a) Hemodynamic changes:
• Irrespective of the nature of injury, the immediate response is
vasoconstriction of arterioles which may last for few seconds to few
minutes, followed by persistent progressive vasodilation.
• This phase involves mainly arterioles and also venules & capillaries,
resulting in increased blood volume in the injured area giving redness
and warmth at that site.
• Along with blood, there is leak of plasma into the extravascular
compartment causing local swelling.

• Because of the increased concentration of red cells and blood
components at a place, the flow of circulation slows (stasis) down, and
the leukocytes move to the periphery of the vessel wall called
margination and later migrate through the loosened gaps between the
endothelial cells into the extravascular space - called emigration.
• These features thus elicit the classical signs of inflammation redness,
warmth, swelling & pain.

b)Altered Vascular Permeability:
In acute inflammation the normal intact tight endothelial cells of the
vessel walls become loose & leaky. These gaps in the endothelial cells are
brought about by certain factors as-
• Contraction of endothelial cells mediated by histamine, bradykinin and
some other chemical mediators.
• Retraction of endothelial cells-mediated by cytokines like interleukin,
IL-1 TN tumor necrosis factor etc.
• Bacteria, radiation or thermal injury
• Release of proteolytic enzymes

II. Cellular Events:
• The cellular reaction of inflammation also consists of two steps, which
are as follows:
• A) Exudation of leucocytes.
• B) Phagocytosis.

A) Exudation of leukocytes:
• a) In the normal blood flow, the cellular elements (RBC, WBC, platelets)
move in the centre of the vessel while plasma remains close to the vessel
wall.
• In inflammation due to stasis of blood, the cells increase in number &
widen up the central zone.
• The plasma layer is narrowed due to the plasma leak & also decreases in
amount. As a result the leukocytes i.e., neutrophils etc. come close to the
vessel wall- and this phenomenon is known as pavementing.

• b) Adhesion phase: The neutrophils then come in contact with endothelial
cells and adhere to them with the help of adhesion molecules - selectin,
Integrins & ICAM-1, 2.
• c) Emigration: The neutrophils move along the endothelial cells till a gap
is found & then they come out with the help of pseudopods & proteolytic
enzymes & the cells emigrate or move out into the extra vascular space.
In addition, red cells also escape through the gaps called diapedesis
giving a blood tinged appearance to the inflammatory exudate.

• d) chemotaxis: The process by which leukocytes migrate from the blood
vessel to the injured site is called as chemotaxis.
• This phenomenon is brought about by chemokines released by the
damaged tissue which includes arachadonic acid metabolites, lysosomal
enzymes etc. attract leukocytes to the injured sit
• The chemoattractive agents will bind to specific receptors on the suface
of leukocytes.
• This bondings will activate several responses in leucocytes which
normally are a defense mechanisms of the leukocytes function. This
activation of leukocytes is referred to as leukocytes activation.

• Such a activation causes release of enzymes, cytokines, adhesion
molecules.
• B) Phagocytosis: It is the process of engulfment of solid material by the
cells, and the cells which perform this function are phagocytes. The
phagocytes are (a) Neutrophils (b) Circulating monocytes and (c) Tissue
macrophages.
• The process of phagocytosis involves certain steps as follows:
• a) Recognition and attachment stage.
• b) Engulfment stage.
• c) Degranulation stage.
• d) Degradation or Digestion stage.

• It comprises of three stages:
• 1. Stage of recognition and attachment: The leukocytes will be able to
recognize the offending pathogen only when they are coated with
This process is called as
protein substance called opsonin.
opsonization.
• The common opsonin's include:
• Fe fragment of immunoglobulin
• Complement fraction C3
• Collections

• Stage of engulfment: The leukocytes have cell surface receptors for the
opsonins.
• Once the receptor is occupied by the opsonin, the contractile proteins
of the cell gets activated and it put forth cytoplasmic extensions called
the pseudopods which slowly engulfs the organism and completely
surrounds it. This is called phagosome.
• By this process, the organism gets internalized within the cytoplasm of
the leukocyte.
• Within the cytoplasm the phagosome is slowly moved close to the
lysosome of the leukocyte and they both fuse to form the
phagolysosome.
• After the fusion, the contents of the lysosome are released into the
phagosome which activates the killing process

• Stage of killing and degradation: Killing is usually done by two
processes. They are
• i. Oxygen dependent mechanism:
• The generation of the free oxygen radicals occurs due to the activation
of NADPH oxidase which generates a superoxide free radical.
• This undergoes spontaneous dismutation and gets converted to
hydrogen peroxide.
• The hydrogen peroxide in the presence of an enzyme called
Myeloperoxidase gets activated to another radical called hypochlorite
which is a potent microbicidal agent.
• Nitric oxide is another free radical generated which can kill the
microbes. The nitric oxide combines with superoxide to form
peroxynitrite which is a powerful bactericidal agent.

• ii. Oxygen independent mechanisms: The leukocytes will also be able to
kill the offending pathogens without the generation of free oxygen
mechanisms. They
radicals. These are called oxygen independent
include:
• » Bactericidal permeability increasing factor
• » Lysozyme-present in tears and prostatic secretions
• » Lactoferrin

Chemical mediators of inflammation
• The origin of mediators can be from cells, the plasma or damaged
tissue.
• Most of the mediators present in the plasma are in the inactive form
• Factors which trigger active mediators are-
- microbial products or damaged tissue
- Host proteins- complement system, kinin system, coagulation system

• General features
• Synthesized by cells and plasma
• Short duration of action
• Acts through the specific receptors on the cell
• Can act on the same cell (autocrine)
• Tightly regulated action
• May have harmful effects

Classification
• Cell derived mediators
• Plasma derived mediators

MORPHOLOGYAND SYSTEMIC
EFFECTS OF ACUTE INFLAMMATION
Some of the morphologic varieties of acute inflammation are described
as follows.
• a) Serous Inflammation: Manifested as oozing of thin fluid at the site
of injury. This fluid is derived from plasma or secretions of
mesothelial cells which cover the peritoneal, pericardial and pleural
cavity causing effusions. It could also be seen in burns or viral
infections causing blisters.
• b) Fibrinous Inflammation: When the injury is large and vascular leaks
are wide, apart from RBC & WBC, plasma & fibrinogen also passes
out into the tissue. Such a type of inflammation is seen in body
cavities, meninges etc.

• c) Suppurative Inflammation: When acute inflammation is associated
with superadded pyogenic (pus forming) bacteria, it results in tissue
necrosis. A cavity is formed of necrotic tissue and is filled by exudate of
necrotic tissue or pus and this process of formation of abscess is called
suppuration.
• d) Cellulitis: It is a diffuse inflammation of soft tissues.
• e) Ulcer: Ulcers are local defects on the surface of an organ or tissue
caused by sloughing off the inflammed necrotic tissue. Ulceration can
occur when tissue damage occurs on (or) near a surface. Commonly
seen in gastro intestinal system - from oral cavity to the rectum, on skin
surface etc.

• f) Bacterial Infection of the blood: This results due to invasion of the
blood stream by pathogenic bacteria causing conditions as follows-
• Bacteriaemia: Few numbers of bacteria are present in the blood. Blood
culture is needed to detect the organism.
• Septicaemia: Rapidly multiplying highly pathogenic bacteria are
present in the blood - causing systemic effects like fever, multiple small
hemorrhages, neutrophilic leucocytosis, shock etc.
• Pyaemia: Is the spread of small septic thrombi in the blood which cause
effects due to vessel blockage at a particular site. May result in pyaemic
abscesses (or) septic infracts.

CHRONIC INFLAMMATION
• Inflammation of prolonged duration with more tissue destruction and
occurrence of parallel healing process.Achronic inflammation may-
• Follow an acute inflammation-due to persistence of the injurious
stimuli or interference with healing process
• Follow repeated episodes of acute inflammation, e.g., chronic
cholecystitis following repeated acute cholecystitis
• Persistence of the microorganism-interference in the process of killing,
eg., tubercle bacilli, Treponema pallidum
• Prolonged exposure to non-degradable toxic substances, e.g., silica,
talk
• Immune mediated de novo process, eg: autoimmune diseases

General Features of Chronic Inflammation
• Infiltration by of the macrophages (epithelioid cells) and multinucleate
giant cells.
• More tissue destruction by the action of the proteolytic enzymes
released by the macrophages.
• Repair of the inflamed area by proliferation of blood capillaries and
fibroblasts and eventual healing by fibrosis.

Macrophage in chronic inflammation
• When the monocyte is activated converted to macrophage
• Macrophages secrete protease, free oxygen radicals, arachidonic acid
metabolites, growth factors, cytokines etc

Chronic granulomatous inflammation
• is a distinct pattern of chronic inflammation characterized by the
presence of activated macrophages called epithelioid cells with/
without giant cells, necrosis and fibrosis.
• Pathogenesis: This inflammatory reaction occurs due to presence of a
poorly digestible substance by the macrophage of immune mediated
reaction by the T lymphocytes.
• Granuloma: It is referred to as a collection of epithelioid cells
surrounded by a collar of lymphocytes, occasional plasma cells and
fibroblastic cell. It is a tiny lesion about 1 mm in diameter.

• Epithelioid cell: It is an activated macrophage with indistinct
cytoplasmic outlines and abundant pale pink granular cytoplasm with
oval vesicular nuclei. The nuclei take the shape of a foot print in
cytological preparations. Since, this cell has got a resemblance to that
of an epithelial cell it is named so. Under electron microscope, an
epithelioid cells have got abundant endoplasmic reticulum, Golgi zone
and mitochondria. It is a
phagocytic than
metabolically active cell but weakly
a macrophage.

• Giant cells: They are larger cells with multiple nuclei usually formed
by the fusion of the epithelioid cells. The number of nuclei may vary
from 20-40 and the pattern of arrangement of the nuclei also differs.
The common types of giant cells are the following
• Langhan's giant cell: The nuclei are arranged along the cytoplasmic
outlines on one side of the cells. This pattern is referred to as horse
shoe or inverted necklace type. This giant cell is mostly seen in
granulomas of tuberculosis.
• Foreign body type giant cell: The nuclei are clustered to the central
part of the cells.
• Touton giant cells: The nuclei are arranged all round the cell
membrane like a wreath. These are seen in lipogranulomatosis
inflammatory conditions

SYSTEMIC MANIFESTATION OF
CHRONIC INFLAMMATION
• 1. Fever: Fever is usually mild and associated with weakness & loss of weight
• 2.Anaemia: Chronic inflammation is associated with anaemia of varying degree
• 3. Leukocytosis: The increase in total leucocyte count (TLC) is mostly due to an
increase of lymphocytes.
• 4. Parasitic infestations and certain allergic reactions cause an increase in
eosinophils. Rarely leukopenia, decrease in leucocytes is encountered in chronic
inflammation- seen in malnourished or chronic debilitating individual.
• 5.ESR: Erythrocyte sedimentation rate is raised in all chronic inflammatory
lesions.
• 6. Amyloidosis: In Long standing cases, there may be secondary systemic
Amyloidosis - Deposition of acellular protein & damage different systems

INTRODUCTION
• Injury to tissue may result in cell death and tissue damage. Healing is
one of the body response to injury in an attempt to restore the normal
structure and function. The healing can occur by two distinct
processes.
• They are: 1. Regeneration: The injured tissue is repaired by the
proliferation of similar type cells.
• 2. Replacement: The injured tissue is replaced by a specialized
connective tissue called granulation tissue which contains proliferating
blood capillaries

REPAIR BY REGENERATION
• Based on the capacity of regeneration the cells in the body are grouped
as follows

Repair by connective tissue
• This occurs due to proliferation of specialized connective tissue called
the granulation tissue.
• Three phases
• 1. Phase of traumatic inflammation- indicates the inflammatory
responses.
• 2. Phase of demolition-indicates the extent of tissue damage.
• 3.Phase of development of granulation tissue-this is further
of
subdivided into a stage neovascularization and stage of
devascularization.

• Stage of neovascularization: This is characterized by the in growth of
new capillaries and proliferation of specialized fibroblastic cells.
• New vessels sprout from the parent vessels and migrate towards the area
of damage.
• Initially, these vessels are very weak and leaky and later they get
organized and canalized.
• Due to the leaky capillaries, the injured site appears edematous.
• Sprouting of the new vessels occurs due to release of various antigenic
factors, such as vascular endothelial growth factor (VEGF); Platelet
derived growth factor [PDGF] and Transforming growth factor-Beta.

• Neovascularization is accompanied by the proliferation of plump
myofibroblast cells which have more abundant granular cytoplasm and
contractility. These cells are responsible for the contraction of the
wound area to be repaired.
• Stage of devascularization: Once the healing process is over, the new
blood vessels gets organized and deposition of collagen replaces the
fibroblastic cells

Wound healing
• Wound healing can be of two types based on the nature of wound
• Healing by primary union
- clean surgical wounds
- clean and sharp opposing edges
- minimal tissue loss
- no contamination
• Healing by secondary union
- larger wounds
- gaped opposing edges
- more tissue loss
- infected wound

Healing by primary union
• A) Immediate response: Immediately after injury, the site of injury by
incision, is filled with blood which clots and tries to seal the gap. This
dehydrates & forms the scab that covers the wound.
• B) Inflammatory Response: Within 24 hours, acute inflammatory cells
neutrophils appear at the margin of the incision & slowly move towards the
fibrin clot. By 3rd day, macrophages replace the neutrophils.
• C) Epithelial changes: within 24 to 48 hours the basal epithelial cells of the
epidermis start to move towards the cut margins in the centre & fuse
beneath the dry scab. Within 48 hours the wound has a layer covered by the
epithelium, with underlying granulation tissue.

• d) Granulation tissue: slowly & progressively invades the incision
space the epithelial cells proliferate & thicken the and epidermis. By
5th day incision space is filled by granulation tissue & the epidermis
recovers its full thickness & differentiation along with surface
keratinisation.
• e) Organisation: By 2nd week, collagen and fibroblasts increase in the
area, with disappearance of inflammatory cells, edema and vascularity
and by the end of one month, a well organised scar is formed. After 1-3
months, the scar decreases in size and changes from red vascular to a
permanent pale & avascular scar.

HEALING BY SECOND INTENTION.
(Secondary Union)
• Healing process in secondary union is slower as the tissue defect is
larger. The basic healing mechanism is similar to that of primary union
with few differences, in the sense that, healing takes place from the
wide base upwards as well as from the margins inwards.
• Epithelial proliferation takes longer time to cover the wide gap
completely, than the primary healing and the inflammatory response is
much greater, than the healing by primary intension

• Granulation tissue and degree of inflammation is greater. Granulation tissue is
formed by fibroblasts and neovascularization from the adjoining viable structures.
This granulation when newly formed, appears red, granular, and fragile. With time it
becomes pale due to less of vascularity and more of collagen.
• Wound contraction: This is an important feature which differentiates secondary
healing from primary healing. Myofibroblasts (altered fibroblasts) which are present
in the granulation tissue are required for wound contraction. By contraction of these
cells, the gap between the two edges is decreased markedly.
• Scar Formation: As repair continues number of vascular channels decrease, with an
increase in collagen, mixed with fibroblasts resulting in scar formation. As the scar
matures, it becomes pale and avascular, incision are lost permantely.

Factors that influence wound healing
• A) local factors
• Type, size
• Location of wound
• Vascular supply
• Infection
• Ionizing radiation
• Ultraviolet light
• Foreign bodies
b) systemic factors
- circulatory status
- infection
- nutrition
- hormones
- diabetes
- hematologic defects

INTRODUCTION
• Normal fluid and electrolyte balance – healthy tissue
• 60% of body weight is water

• The mechanism by which all this above components ae maintained in
appropriate amount and in their correct form is called homeostasis.
• Any drastic changes in the homeostasis leads to disorders such as
follows:
- heamodynamics - edema, congestion, shock
- haemostasis- heamorrhage and thrombosis

Thrombosis
• It is defined as the formation of solid mass or plug from the
constituents of blood within an uninterrupted living circulation.
Welch (1887)
• Useful to arrest the excessive loss of blood.
• But when it occurs in an uninterrupted living circulation, it leads to
pathological consequences.
• Two most common sequelae of thrombi are
- Ischemic injury – due to block in the blood supply
- embolism – a portion of thrombi may get dislodged and carried
along the blood stream to a distant site.

• Normal hemostasis:
- there are three important contributors for normal hemostasis
• They are
- blood vessel wall
- platelets
- coagulation system

• Sequence of events in normal hemostasis:
- injury to vessel wall
- brief vasoconstriction
- endothelial injury
- exposure of thrombogenic endothelium
- adherence of platelets to subendothelium
- activation of platelets
- release reaction of platelets and aggregation
- Primary platelet plug
- Release of tissue factors
- Activation of the coagulation cascade
- Formation of fibrin clot (secondary hemostatic plug)

• Role of Vessel Wall
• The endothelium is a very versatile cell with both procoagulant and
anticoagulant properties. Both are kept in a well-balanced state. Any
disturbance to the normal functioning of the endothelium may tilt the
balance and result in formation of thrombi.
• Prothrombotic functions:
- synthesis of Von Willebrand factor which binds platelets to
subendothelium.
- secretion of tissue factor which activates extrinsic pathway
- inhibits plasminogen activator which prevents fibrinolysis

• Anti thrombotic functions:
- secretion of prostacycline, nitric oxide andADPase
- secretion of anticoagulant protiens such as antithrombin III,
thrombodulin and protein C
- synthesis of plasminogen activator which promotes fibrinolysis.

• Role of Platelets
• The platelets are tiny anucleate cells of the blood which play a vital role
in hemostasis.
• The platelets contain two types of granules: - alpha and delta granules
which mediate their function.
• Functions are:
1. Adhesion: The platelets adhere to the sub- endothelial through the
vWF The surface glycoprotein lb (Gp Ib) binds with the Von Willebrand's
factor (vWF).

2.Activation and secretion: After adhesion, the platelets undergo
activation by the release of ADP, calcium and other substances and
actively secrete the contents of the granules which cause recruitment of
more platelets to the site and its activation.
3.Platelet aggregation: Due to release of ADP, the platelets adhere well
to form a primary hemostatic plug in the site of endothelial damage. It
also leads to the expression of the phospholipid complex in its surface
which activates the intrinsic pathway of coagulation.

• Role of the Coagulation System
• The main function of this system is to convert soluble fibrinogen to solid fibrin.
• It comprises predisposing factors which leads to formation of three pathways-
intrinsic, extrinsic and common.
• The intrinsic pathway is activated by the surface contact and it leads to the
sequential activation of factor XII, XI, IX, and VIII and X.
• The extrinsic pathway is activated by the release of tissue factors which act on
factor VII and subsequently on factor X.
• The common pathway starts with factor X and sequentially activates factor VII
and finally converts fibrinogen to fibrin.
• The fibrin is laid between the platelets of the primary plug, such as the cement
layering between the bricks and forms the secondary (permanent) hemostatic plug.

• The fibrin plug seals the vascular damage until there is regeneration of
the endothelial cell.
• Once the regeneration is complete, the intrinsic fibrinolytic system
gets activated and released plasmin which acts of the fibrin and breaks
fibrin into fibrin degradation products and the vessel wall returns to
normalcy.

Thrombogenesis:
• The three most important predisposing factors for thrombogenesis are:

• 1.Endothelial injury
• 2.Alterations in the flow of blood
• 3. Hypercoagulability of blood
• These are referred to as Virchow's triad.

Endothelial Injury
It is a dominant factor in thrombogenesis.
The most common causes for endothelial injury
• Atherosclerosis
• Myocardial Infarction
• Valvulitis
• Vasculitis
• Traumatic-indwelling catheters, extremes of temperature
• Hemodynamic stress-hypertension
• Toxins-homocysteine
• Hypercholesterolemia
• Smoking
• Radiation

Alterations in the Flow of Blood
The two main alterations in the flow of blood are turbulence and stasis.
1. Turbulence-abnormal haphazard flow of blood within the blood
vessel
2. Stasis – abnormal pooling of the blood within the vessel

• Any alteration in the flow of blood leads to the disruption of the axial
flow of blood. It brings the platelets close to the endothelium, promotes
endothelial cell activation, prevent dilution of the activated clotting
factors and retard the inflow of clotting factor inhibitors.
• Turbulence usually causes arterial and cardiac thrombi and stasis leads
to venous thrombi. The common predisposing factors for alterations in
flow of blood is
aneurysms
hypertension,
and
ulcerated atheromatous plaque,
dilated cardiomyopathy.

Hypercoagulability of Blood
• There is increased predisposition to hypercoagulability in these groups
of disorders. They can be classified as primary and secondary causes.
Some important disorders are
Primary hypercoagulability disorders
• Mutations of factor V
• Deficiency of antithrombin III disorders
• Hereditary homocystinuria

Secondary hypercoagulability disorders
• Prolonged immobilization
• Myocardial infarction, atrial fibrillation
• Massive tissue damage
• Intravascular coagulation
• Antiphospholipid syndrome
• Cardiomyopathy

Pathology of Thrombus
• Sites of thrombi: Thrombi can occur anywhere in the cardiovascular
system mostly in the cardiac chambers, valve cusps, arteries, veins and
capillaries. They are located at the sites of endothelial damage.
• Morphology: Thrombi can be grouped into red thrombi, white thrombi
and mixed thrombi based on the morphology.

• Cardiac thrombus: Thrombi can be seen in the cardiac chambers and on
the valve leaflets. The thrombi of the cardiac chambers are referred to
as mural thrombi and of the valve leaflets are referred to as thrombotic
vegetations.
• Cut section of a mural thrombi shows alternating layering of dark red
and pale white areas thrombi which are called as the lines of Zahn.
• Thrombi are usually seen over an infracted area and thrombi of the left
atrium may cause sudden obstruction to the outflow tract and it is called
as Ball Valve Thrombi.

• Fate of thrombus
- propagation – by means of extension or growth
- emboli formation – detachment of a portion of thrombus and travels
to other site
- dissolution – by means of fibrinolytic system, which clears the clot
- organization- gets corporate into the vessel wall and formation of a
new channel may occurs
• Clinical significance:
- Ischemia and edema of tissues distal to obstruction
- emboli can cause death

EMBOLISM
• Definition: Embolus is a detached intravascular mass carried by the
blood to a distant site from the point of origin.
• It can be solid, liquid or gaseous mass.
• Two types:
• Systemic embolism
• Pulmonary embolism.
99% are due to dislodgement of thrombus, therefore are called
thromboemboli

Other special types
• Air embolism
• Amniotic fluid embolism
• Fat embolism
Systemic Embolism:
• Thrombi arising within the heart, travel and travel through the arterial
circulation and are associated with the following:
• Ex: Myocardial infarction. Rheumatic heart disease. Atrial fibrillation.
Ulcerated atherosclerotic plaques

Pulmonary Thromboembolism
• Seen in 20-25/1,00,000 hospitalized patients.
• Pathogenesis: About 96% of the emboli originate from the deep veins of
the leg.
• The fragmented thrombi are carried by the venous channels into the
right side of heart, from which it enters the pulmonary arteries.
• If it is very small, it passes through the smaller branches and gets
lodged in the alveolar vessels.
• If it is very big it can occlude the bifurcation of the pulmonary trunk
like a saddle and cause sudden death. This embolism is called saddle
embolism

• In persons with intra-arterial septal defect or interventricular septal
defect the emboli pass from the right side of the heart to the left side
and thereby enters the systemic circulation. This is called a paradoxical
embolism (a venous embolus entering systemic arterial circulation).
Pathology
• Only 10% of the emboli causes pulmonary infarction, because lungs
have double vascular supply from the pulmonary and bronchial
system.
• Saddle embolus causes sudden death due to acute dilatation of the
right heart (acute corpulmonale).

Morphology: It involves the lower lobes of lung.
• Produces a wedge-shaped infarct which is
hemorrhagic.
grayish brown and
• The overlying pleura is thick and fibrinous.
• The infracted are later undergo fibrosis and forms a scar tissue.
• Rarely infection may occur on an infracted area producing an abscess.
Clinical Features
• Patients present with chest pain, difficulty in breathing, shock, cough,
tachycardia, tachypnea, hemoptysis and pleural pain.

Prevention
• It can be avoided by early ambulation of the bed ridden patients, giving
isometric leg exercises and prophylactic therapeutic measures.

Arterial Embolism (Systemic Thromboembolism)
• About 80% arises from an underlying mural thrombi. The emboli enter
the systemic circulation and gets lodged in the brain, kidney, mesentery
and lower extremities. The effects depend on the vessel occluded and
tissue vulnerability to ischemia.

Fat embolism
•Obstruction of the capillaries by globules of fat.
Most common predisposing factors include:
• Multiple fracture of long bones
• Soft tissue trauma
• Extensive burns .
• Pancreatitis

• Pathogenesis: Mechanical obstruction induced by the microaggregates of
fat or release of free fatty acids from the fat causes toxic damage to the
endothelium and thereby induces a thrombus and subsequent
embolization.
Clinical Features
• Patients present with chest pain, difficulty in breathing, shock, cough,
tachycardia, tachypnea, hemoptysis and pleural pain

SHOCK
• Circulatory collapse as a result of wide spread hypoperfusion of
tissues due to reduction of cardiac output or reduced circulatory
volume.
Types of shock:
1. Cardiogenic shock
2. Hypovolemic shock
3. Septic shock
4. Neurogenic shock
5. Anaphylactic shock

• Cardiogenic shock:
Whenever there is a failure of cardiac pump > reduction in cardiac
output>shock
• Hypovolemic shock:
Due to fluid and blood loss as in severe burns, acute GE, trauma where
there is reduction in blood and plasma volume>shock
• Neurogenic shock:
Vasodilation occurring in anaesthesia accidents, spinal cord injury.

• Septic shock
• Overwhelming Bacteremic infections by gram negative/positive
organism or fungi vasodilation, pooling of blood lead to DICshock.
• Pathogenesis: Endotoxins of the bacterial wall, combine with the LPS
binding protein in the serum, binds to CD14 of leukocytes, and
endothelial cells activation of cascade release of mediators both
cytokines & other arachidonic acid metabolites → in turn causes
capillary thrombosis, intra vascular coagulation and vasodilation.

Organ Changes in Septic Shock
• Heart: Chamber dilatation and suppression of myocardial function
• Lungs: Diffuse alveolar damage presenting as acute respiratory distress
syndrome
• Kidney:Acute tubular necrosis presenting as acute renal failure
• Brain: Features of hypoxic encephalopathy

Stages of Shock
• The evolution of shock can be divided into three different stages.
• They are:
• 1. Initial non-progressive phase
• 2. Progressive decompensated phase
• 3. Irreversible phase

1. Initial non-progressive phase: This is the initial stage of shock where
the body tries to compensate for the tissue hypoperfusion by activating
the neurohormonal compensatory mechanisms. They include:
• Activation of baroreceptors
• Secretion of catecholamine’s
• Activation of renin angiotensin aldosterone axis
• Release of anti-diuretic hormone
• Stimulation of the sympathetic system

• The blood supply is diverted from the periphery to the brain and
kidney to maintain adequate functioning of these organs. It manifests
clinically as cool and clammy extremities, thin thready pulse, pallor of
skin and tachycardia. Patients with septic shock will have
vasodilatation in contrast to vasoconstriction seen in other types of
shock.
2.Progressive decompensated phase: The shock may progress from
the initial phase to this phase due to persistence of the cause of shock
and therapeutic in correction. This leads to persistent oxygen deficit.

• There is a shift from the aerobic metabolism to anaerobic metabolism
which results in excessive production of lactic acid and induces
intracellular acidosis. There is fall in the pH of the blood which causes
vasodilatation. This interferes with the functioning of the vital organs.
The clinical manifestation of this phase are fall in the urinary output
(Oliguria); patient is drowsy and confused, fall in the blood pressure,
and bradycardia.
• 3. Irreversible phase: The predisposing factors are mostly severe shock
and failure of the compensatory mechanisms It results in diffuse
hypoxic cell injury which produces multiorgan dysfunction

TREATMENT:
• Supportive therapy
• Control of infection in septic shock
• Restoring fluid and electrolyte balance
• Proper ventilation to prevent respiratory distress
• Preventing renal shut down

DISTURBANCES OF BODY
FLUID AND
ELECTROLYTE BALANCE

EDEMA
• is defined as an abnormal and excessive accumulation of fluid in the
interstitial space.
• The term is derived from a Greek word oedema which means swelling.
• There are various terms used to describe edema of various sites.
• Edema can be further categorized into local and general
• The generalized edema is called asAnasarca.

• Edema of the serous cavities is examples for localized edema and they
are referred according to the space involved:
• Pleura-hydrothorax (Pleural effusion)
• Pericardium-hydropericardium (pericardial effusion)
• Peritoneum-hydroperitoneum (ascites)
• Clinically edema can be grouped as pitting and non-pitting edema.
If the edema fluid could be displaced by applying pressure then it is
called pitting edema e.g., cardiac and renal edema
if the fluid could not be displaced it is non- pitting edema, e.g.,
myxedema, elephantiasis.

• Pathogenesis:
• Edema is caused by mechanism that interferes with the normal balance
of the intravascular and extravascular fluid transfer.
• The two main driving forces for the transfer of fluid in and out of the
vessels are the intravascular hydrostatic pressure and the colloid osmotic
pressure (Plasma oncotic pressure).
• Normally, at the arteriolar end of vessel fluid escapes into the
extravascular space due to increased hydrostatic pressure. This fluid
enters the vessel back at the venular end due to the plasma oncotic
pressure.
• A minor proportion of the fluid enters the lymphatics of the interstitium.
So normally, there is a perfect balance of the fluid transfer in and out of
the vessel. This is referred to as the Starling's Forces.

TRANSUDATE AND EXUDATES
ETIOPATHOGENISIS:
• Pleural, pericardial and ascitic fluids are formed as an ultrafiltrate of the
fluid of blood and plasma. Normally, there is an exchange of fluid between
the vascular and tissue spaces and the body cavities. Equal volume leaves
and enters these spaces, hence maintaining a constant volume.
• Most of this fluid contains water and certain small molecules like salt,
glucose, urea etc. Large molecules like Red blood cells, plasma proteins,
normally stay within the vascular lumen. Smaller molecules move in and
out easily, whereas larger molecules need to get drained off via the
lymphatics and back into the blood stream.

• This flow of fluid in and out of spaces is influenced by certain factors,
such as-
• 1. Hydrostatic pressure in the capillaries and veins
• 2. Colloid osmotic pressure in plasma
• 3. Capillary permeability
• 4. Lymphatic drainage system.

• Any abnormality in these factors will result in the accumulation of the
fluid in the various cavities. Abnormality in the above factors could be-
• 1. Increased venous pressure
• 2. Decreased plasma colloid osmotic pressure.
• 3. Increased capillary permeability.
• 4. Obstruction to lymphatic drainage.
The fluids are thus segregated into 'Transudate' and 'Exudate'. The
differences between these 2 types of fluids are as follows.

• Meaning of the term neoplasia is "new growth" (neo-new, plasia-
growth).
• Oncology (oncos-tumor, logos-study) is the scientific study of
neoplasms.
• The mostly widely used terminology for indicating neoplasia is cancer
(meaning crab-as the disease infiltrates the organs like the crab).

• Definition: It is an abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of normal tissue and persists in
the same excessive manner even after the cessation of the stimuli which
has evoked the change. In simple terms, it is an autonomous and
purposeless proliferation of cells.

• Nomenclature: The common terminologies used in neoplasia are
benign tumors and malignant tumors
• Every tumor has got proliferating cells with a supporting stroma. Most
of the benign tumors are labeled according to the nature of the
proliferating cells with a suffix of oma

Definition
• It is defined as localized area of necrosis of lung tissue with
suppurative degeneration.

Etiological agents:
• Aspiration of foreign body: Most common causes are aspiration of
foreign bodies food particles, decaying tooth, gastric contents, etc.
This is seen in children during play, patients under general anesthesia,
coma and alcoholism.
• Spread of infection: Patients with severe bronchopneumonia,
bronchiectasis, pulmonary tuberculosis, may develop of lung abscess
It can also occur to spread of infection from empyema, suppurative
pericarditis.
• Secondary to obstruction with tumors and foreign body.
• Septic embolization: Due to lodging of the septic emboli from cases of
infective endocarditis and other causes.

Pathology
• Lung abscess secondary to aspiration of foreign body is more common in
the right lobe of lung because the right bronchi are in direct continuation of
trachea and they are often solitary whereas the abscess from other causes
are usually multiple and scattered through the lung.
• Grossly the abscess measures from few millimeters to 5- 6 cm. The wall is
usually shaggy with ragged margins.
• Microscopically it shows areas of suppurative necrosis with surrounding
acute and chronic inflammatory reaction.

Clinical features
• The clinical manifestations include high fever with chills, malaise,
cough with purulent sputum and hemoptysis. Clubbing of fingers and
amyloidosis occurs in long standing cases

Definition
• It is a granulomatous inflammation caused by Mycobacterium
tuberculosis
• It is very common infectious disease in developing and under
developed countries.
• Roughly around 1.7 billion people affected by this disease with an
incidence of 8-10 million new cases each year and death rate of 1.7
million deaths per year.
• It is one of the leading infectious causes for death.

Organism: This disease is caused by slender aerobic rods which grow in
straight/branching chains.
• The bacteria have a waxy cell wall with mycolic acid which gives the
property of acid fastness.
• The most common causative organisms are:
• M. tuberculosis: Pulmonary tuberculosis
• M. bovis: Intestinal and oropharyngeal tuberculosis.

Predisposing factors:
• Poverty
• Over crowding
• Chronic debilitating illness
• AIDS/Immunosuppression
• Hodgkin's lymphoma
• Chronic lung disease - silicosis
• Chronic renal failure
• Malnutrition
• Alcoholism

Pathogenesis
• Primary Pulmonary Infection:
• This occurs usually in children who have not been previously exposed
to tuberculosis or are vaccinated against it.
• Inhalation of organisms presents in fresh cough droplets or in sputum
from an open case of pulmonary tuberculosis, enter the lung and get
lodged at the periphery of the lung which receives greatest volume
flow of inspired air.
• The primary lung infection is usually called as Ghon focus which is 1-
1.5 cm diameter

• On 1" exposure, tubercle bacilli evoke a non specific neutrophilic
inflammatory response.
• During this period, bacilli enter phagocytes, and multiply and drain via
lymphatics, to the hilar nodes.
• The primary lung lesion, lymphatics and the involved hilar lymph node
are called the Primary complex (or) Ghons complex.
• Healing can occur at this stage, leaving behind calcified lymph nodes, or
the disease may spread via the blood stream to distant sites.

Pathology:
• There are usually two forms of tuberculosis. They are primary and
secondary tuberculosis.
• Lungs are involved in both forms of tuberculosis.

Primary tuberculosis:
The most common sites for primary tuberculosis are the following:
• Lung with enlarged hilar lymph node (most common)-Ghon's complex
• Intestine (Ileum) with enlarged mesenteric lymph node
• Tonsils with enlarged jugulodigastric lymph node.
In the lungs it usually involves distal air spaces of lower part of upper
lobe and upper part of lower lobe, close to pleura (subpleural)
characterized by area of grayish white consolidation of size 1-1.5 cm with
the involvement of regional nodes.
95% of cases undergo complete healing and about 1% of the cases
develop progressive fibrosis and calcification which is referred to as
Ranke complex

Secondary tuberculosis:
• Secondary tuberculosis can occur due to reactivation of the primary
infection or occurrence of reinfection.
• The initial lesion is a small focus of consolidation <2 cm occurs 1-2 cm
from the apical pleura.
• The lesion is sharply circumscribed, grayish white areas with caseation.
It heals by fibrosis and calcification.

Cavitatory tuberculosis :
• This is mostly seen in elderly and in immuno- compromised
individuals.
• It presents as an expanded apical lesion with cavitation. The wall of
the cavity is irregular and shaggy.
• It may erode into bronchus with the erosion of bronchial vessels
resulting in hemoptysis.
• The cavities heal with irregular fibrous scarring and collapse.

Miliary tuberculosis:
• Due to the dissemination of the infection through
lymphohematogenous route to form multiple tiny lesions called the
Miliary Tuberculosis. Expand to involve large areas. The lesions
resemble millet seeds and named so. The miliary tuberculosis can
confine to lungs or undergo extrapulmonary spread. The common
organs involved are liver, bone marrow, spleen, adrenals, meninges,
renal, fallopian tubes and epididymis.

Pleural involvement:
• Involvement of the pleura is one of the common manifestations of
tuberculosis. The common pleural lesions are pleural effusion,
empyema and obliterative pleural fibrosis. Other forms of pulmonary
tuberculosis are Endobronchial, Endotracheal and Laryngeal
tuberculosis.

Extrapulmonary tuberculosis:
• Tuberculosis can involve lymph nodes, Intestine - (mostly terminal part
of ileum), Kidneys (Renal tuberculosis), Adrenals (Addison's disease),
Bone (TB osteomyelitis), Fallopian tubes (TB salpingitis),
Endometrium (TB endometritis) (Fig. 13). Vertebrae (Pott's disease)
and formation of cold abscess in the paraspinal region, abdomen and
pelvis and meninges (TB meningitis)

Clinical features:
• The following common clinical symptoms associated with tuberculosis
include Fever - Low grade - remittent, malaise, anorexia, weight loss,
night sweats, productive cough, haemoptysis, pleuritic pain and
extrapulmonary manifestations.

Diagnosis of tuberculosis:
They include:
• History and physical signs
• Erythrocyte sedimentation rate
• - Radiography
• Acid fast smears/culture
• - Mantoux test (PPD) and ESR PCR amplification of M. tuberculosis
DNA
• - FNAC/Tissue histopathology.

Definition:
• These are group of pathological conditions of lung characterized by
chronic partial or complete obstruction of airway at any level from
trachea to the smallest airway resulting in functional disability.
• There are four important disorders categorized under this heading.
They include:
• 1. Chronic bronchitis
• 2. Emphysema
• 3. Bronchial asthma
• 4. Bronchiectasis

Chronic bronchitis :
• It is the most common form of COPD and is a common occupational
respiratory disease.
• Definition: Presence of persistent cough with production of sputum for
a period of at least three months in two consecutive years.
• Etiology: The most common etiologic agents are cigarette smoke and
atmospheric pollution. This disease is more common in individuals
working in cotton and plastic factories and people who are exposed to
organic and inorganic dust particles.

• Pathogenesis: There is marked hypertrophy and hyperplasia of the mucus secreting
glands of the bronchi with thickening of the bronchial wall with associated chronic
inflammatory response of the bronchial wall leading to partial airway obstruction.
• Pathology: On examination of the lung the bronchial walls appear thick with the
lumina showing mucus plugs. Microscopically there is marked hypertrophy and
hyperplasia of the mucus secreting glands of the bronchi with peri bronchial fibrosis.
• Clinical profile: This is a disease of middle-aged men characterized by persistent
cough with expectoration, recurrent respiratory tract infections and difficulty in
breathing. In long standing cases the patient may develop cyanosis and cardiac
failure (cor pulmonale).

Emphysema
• Definition: Abnormal permanent dilatation of the air spaces distal to
the terminal bronchiole with associated destruction of the alveolar wall.
• Emphysema has to be differentiated from a closely related pathology
called Overinflation. This is characterized by overinflated alveoli
without destruction of the alveolar wall. Usually seen in senility, close
to obstructive lesions, surgical complication and compensatory
mechanism when a portion of lung is resected.

Etiopathogenesis:
• The major etiopathological factor involved in the pathogenesis of emphysema is
alteration in the balance of the protease and antiprotease enzyme mechanism.
• The activity of the protease enzymes in naturally checked by the presence of
antiprotease enzymes like the alpha-1 antitrypsin.
• Emphysema can occur due to increased activity of the protease enzymes or due to
the deficiency of the antiprotease enzyme mechanisms.
• The most common causes are smoking, air pollution and congenital deficiency of
alpha-1 antitrypsin.
• Smoking and air pollution activates the protease enzymes mostly elastase which
damages the alveolar wall.
• Smoking also inhibits the activity of the anti-elastase enzymes and thereby acts as a
double edged sword.

Pathology:
• On gross examination the lungs appear more voluminous with rounded
edges. The air spaces appear dilated with formation of subpleural bullae.
Microscopy shows dilated air spaces with destruction of the alveolar
septal wall .

Classification:
• There are four major forms of emphysema based on the portion of the airway
involved.
• They are
• 1. Centriacinar : Involves central portion of the acini of the upper lobe of lung
mostly seen in smokers
• 2. Panacinar : Involves the entire acini and more common in the lower lobe of
the lung. Seen in individuals with deficiency of alpha-1 antitrypsin.
• 3. Paraseptal: It is a localized form of emphysema involving the distal part of
acini close to pleura. It is one of the most common causes for spontaneous
pneumothorax.
• 4. Irregular and mixed pattern: It includes more than one morphological form
of emphysema and usually seen in elderly smokers.

Clinical profile:
• The patient usually presents with severe exertional dyspnea, tachypnea
and barrel-shaped chest. Cough occurs in late stages of the disease
with production of scanty mucoid sputum. Long standing case may
end up with right sided cardiac failure.

Bronchiectasis:
• Definition: It is defined as an abnormal irreversible dilatation of the
bronchi and bronchioles secondary to chronic necrotizing inflammatory
weakening of the bronchial wall.
• Etiopathogenesis: The two main etiopathogenic factors are obstruction
and infection. Obstruction may be induced by congenital defects, foreign
bodies or tumors. Infection occurs secondary to obstruction.

• Classification: Bronchiectasis is classified into two major types based
on the etiologic agents involved and shape of the dilated airway.

Pathology:
• It involves the distal bronchi and bronchioles of the lower lobe of the
lungs. It gives a honeycomb appearance to the lung with dilated airway
traced up to the pleural surface. The airways are irregularly dilated with
mucopurulent material within the lumina.
Microscopically, the bronchial wall is dilated with ulceration and dense
peri bronchial inflammatory cell infiltration with destruction of the wall.
The adjacent pleura is thick and adherent.

Clinical profile:
• Patients usually present with irregular fever with severe cough with
production of copious foul-smelling sputum or hemoptysis. The late
complications include clubbing of fingers, disseminated abscess
formation, amyloidosis (deposition of amyloid protein substance in the
interstitium) and cardiac failure (cor pulmonale).

Bronchial asthma
• Definition: It is defined as a hyperactive airway disease with episodic
reversible bronchoconstriction, manifested as paroxysms of Cough and
wheezing
• It is a very common respiratory illness and affects 4% of the total
world population. There are two main forms of bronchial asthma-
Extrinsic and Intrinsic.

Pathogenesis:
• The disease starts with exposure of the individual to an allergen. The
person becomes sensitized and results in the formation of IgE
antibodies. These antibodies coat the mast cells.
• Re- exposure to a similar antigen triggers the immunological response
and mast cells undergo degranulation and release the cytoplasmic
granules which includes histamine, Eosinophilic chemotactic factor,
prostaglandins and platelet activating factor which causes
bronchoconstriction.
• Repeated similar episodes lead to remodeling of the bronchial wall with
proliferation of the smooth muscle and fibroblasts.

Pathology:
• The lungs appear over distended with the bronchi showing thick viscid
mucus plugs.
• Microscopically the bronchial wall contains mucus plugs with
degenerated respiratory epithelium called the Curschman spiral. It may
also contain numerous eosinophils and diamond- shaped crystals called
the Charcot-Leyden crystals.
• In long standing chronic cases the bronchial wall appears thick with
thickening of the basement membrane with marked edema of the
submucosal glands and infiltration by lymphocytes and plasma cells.
These changes are referred to as airway remodeling.

Clinical features:
• It is characterized by episodes to severe cough with production of
thick viscid mucoid sputum and wheezing Severe and unremitting
form of asthma is
called as status asthmaticus.

Tumors of lung-bronchogenic carcinoma
• It is one of the most common visceral malignancies.
• The incidence of tumors of lung are on a rise due to cigarette smoking
and exposure to environmental pollutants.
• They are more common in the 5-6 decade of life and the incidence is
more in men.

Etiological factors:
• Smoking: There is a positive relationship between smoking and
occurrence of bronchogenic cancers. The risk of lung cancer is 10 times
more in smokers than in non-smokers.
• The risk is dependent on various factors like amount of smoking, pattern
of inhalation and duration of smoking. The cigarette smoke contains
around 1200 carcinogens of which the Important ones are polycyclic
aromatic hydrocarbons, benzopyerene, nicotine, polonium and others.
• Cigarette smoking also induces cancer of other organs like Mouth,
tongue, pharynx, larynx, S esophagus, pancreas, kidney and urinary
bladder.

• Industrial hazards: Exposure to radiation, asbestos fibers, uranium,
nickel, chromium, arsenic, beryllium and mustard gas also induces lung
cancers.
• Air pollution: Exposure to radon gas has a higher risk.
• Genetic causes

Classification:
• The World Health Organization has classified the tumours of the lung
into the following broad categories. They are
• 1. Squamous cell carcinoma
• 2.Adenocarcinoma
• 3. Bronchioloalveolar carcinoma
• 4. Small cell carcinoma
• 5. Large cell carcinoma
• 6. Other tumours: Metastatic tumours bronchial
mesenchymal tumours
• 7. Pleural tumours: Mesothelioma-benign and malignant.
carcinoid,

Pathological changes:
• Most of the tumors occur in the hilar region of lung. It appears as a
localized thickening of the bronchi with piling up of the area to produce
a grayish white mass lesion.
• The lesion usually fungates and erodes the lumina of the bronchi. There
may be areas of necrosis and cavitation mostly in squamous cell
carcinoma.
• Few of the tumors namely adenocarcinoma present as a nodular mass in
the peripheral region.
• The metastatic tumors are usually multiple and scattered through the
lung parenchyma.

• Squamous cell carcinoma-lung: Most common tumor in men. Present
as central hilar mass. Cavitation and necrosis are more common. Has a
slow growth rate.
• Adenocarcinoma: More common tumor in women and non-smokers.
Present as a peripheral nodule with slow growth rate. May also be
associated with old fibrous scars of lung.
• Small cell carcinoma: Highly malignant tumor of lung, presenting as
a hilar mass. Composed of small cells with scant rim of cytoplasm and
round nuclei with finely granular chromatin. These tumor cells secrete
various hormones and so the patients with this tumor present with
various types of paraneoplastic syndromes.

Spread of tumors:
• The bronchogenic tumors can invade the adjacent structures like
pleura, pericardium, mediastinum or undergo a spread through the
lymphatics to the regional lymph nodes and hematogenous spread to
distant organs like the liver, bones, adrenal, brain, opposite lung and
the kidneys.

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