ANIMAL HEALTH LEVEL II

Identifying Pathological Lesions

LO #1- Identify gross pathological lesions and terminologies

1.1. Introduction to general veterinary pathology

Pathology is the study of the way diseases and illnesses develop or the study of the causes and
effects of disease or injury. It investigates the essential nature of disease and is usually
summarized as the study of the functional and morphological changes in the tissue and fluids of
the body during disease.

 Disease is a state in which some part of the body is not functioning properly or it is an
altered (deranged) normal physiological activity of the body or is a condition in which an
individual shows an anatomical, chemical or physiological deviation from the normal.
(Discomfort with environment & body). Pathology gives explanations of a disease by
studying the following four aspects of the disease. This means

 the study of the essential nature of diseases and especially of the structural and functional
changes produced by them studied animal pathology
 something abnormal:
 The structural and functional deviations from the normal that constitute disease or
characterize particular disease the pathology of pneumonia.
 Deviation from propriety or from an assumed normal state of something nonliving or
non-material.

Veterinary Pathology is: The study of animal disease in a variety of species, often with human
implications. Pathology provides the scientific foundation for the practice of medicine by
studying the aetiology and pathogenesis of disease at all levels. It is Crucial in determining cause
of animal disease and its risk to human health (at the forefront of the One Health concept). It also
Studies range from live animals to specific proteins involved in disease.

Pathology is the study of the anatomical, chemical and physiological alterations from normal as a
result of disease in animals. It is a key subject because it forms a vital bridge between preclinical
sciences (Anatomy, Physiology, and Biochemistry) and clinical branches of medicine and
surgery.
Pathology is derived from a Greek word pathos = disease, logos= study. It has many branches,
which are defined as under:

Notes: Health, illness and disease differences are:

 Health is a state of an individual living in complete harmony, with his environment;
surroundings.
 Illness is the reaction of an individual to disease in the form of illness.

1.2. Pathological terminologies

Generally study personnel will find the language that pathologists use perplexing and esoteric.
This is not a reflection on the ability of the study personnel! Although difficult for non-
pathologists to understand, the complex language of pathology is used to convey precisely the
observations made by the pathologist. In general, necrosis, degeneration and vacuolation are
given the suffix ‘-opathy’ (a general term indicating a pathologic necrotic or degenerative
condition in a specific organ). This is preceded by the organ name (generally in Greek),
indicating the tissue or organ affected. An example is ‘nephropathy’, which indicates necrosis or
degeneration in the kidney (‘nephros’). Qualifiers such as distribution, duration, severity and
type of cell involved are used to ‘build a diagnosis’; for example, ‘multifocal, chronic, severe
nephropathy’. The following are some of the general terms that we convey communication
between in the working environmental area of pathology.
 Pathogenesis is the progressive development of a disease process. It starts with the entry
of cause in body and ends either with recovery or death. It is the mechanism by which the
lesions are produced in body.
 Etiology is the study of causation of disease.
 Inflammation: is a protective response to rid the body of the cause of cell injury and the
resultant necrotic cells that cell injury produces. It is the body's mechanism for coping
with agents that could damage it.
 Necrosis: (from Ancient Greek νέκρωσις (nékrōsis) 'death') is a form of cell injury which
results in the premature death of cells in living tissue by autolysis.
 Oedema: also spelled oedema, and also known as fluid retention, dropsy, hydropsy and
swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms
are affected.
 Cancer is a group of diseases involving abnormal cell growth with the potential to invade
or spread to other parts of the body.
 Jaundice: also known as icterus, is a yellowish or greenish pigmentation of the skin and
sclera due to high bilirubin levels
 Homeostasis is the mechanism by which body keeps equilibrium between health and
disease. E.g. Adaptation to an altered environment.
 Diagnosis is an art of precisely knowing the cause of a particular disease (Dia= thorough,
gnosis= knowledge).
 Symptoms: any subjective evidence of disease of animal characterized by an indication
of altered bodily or mental state as told by owner (Complaints of the patients).
 Signs: indication of the existence of something, any objective evidence of disease,
perceptible to veterinarian (Observations of the clinicians).
 Syndrome: a combination of symptoms caused by altered physiological process.
 Lesion is a pathological alteration in structure or function that can be detectable.
 Incubation period is the time elapses between the action of a cause and manifestation of
disease.
 Course of disease is the duration for which the disease process remains till fate either in
the form of recovery or death.
 Prognosis is an estimate by a clinician of probable severity/outcome of disease.
 Morbidity rate is the percentage/ proportions of affected animals out of total population
in a particular disease outbreak. E.g. out of 100 animals, 20 are suffering from diarrhoea.
The morbidity rate of diarrhoea will be 20%.
 Mortality rate is the percentage/ proportions of animals out of total population died due
to disease in a particular disease outbreak. e.g. In a population of 100 animals, 20 falls
sick and 5 died. The mortality rate will be 5%.
 Case fatality rate is the percentage/ proportions of animals died among the affected
animals. In a population of 100 animals, 20 falls sick and 5 died. The case fatality rate
will be 25%.
 Biopsy is the examination of tissues received from living animals.
 Infection is the invasion of the tissues of the body by pathogenic organisms resulting in
the development of a disease process.
 Infestation is the superficial attack of any parasite/ organisms on the surface of body.
 Pathogenicity is the capability of an organism for producing a disease.
 Virulence is the degree of invasiveness of pathogenic organism.

 Morphologic changes refer to the structural alterations in cells or tissues that occur
following the pathogenic mechanisms. The structural changes in the organ can be seen
with the naked eye or they may only be seen under the microscope. Those changes that
can be seen with the naked eye are called gross morphologic changes & those that are
seen under the microscope are called microscopic changes. Some of the morphological
changes are listed as follow:
 Contusions or bruises arise from rupture of blood vessel with disintegration of
extra vassated blood.
 Abrasions are circumscribed areas where epithelium has been removed by injury
and it may indicate the direction of force.
 Erosions: a partial loss of surface epithelium on skin or mucosal surface.
 Laceration: severance of tissue by excessive stretching and is common over bony
surfaces or are produced by cut through a dull instrument.
 Compression injury is produced as a result of force applied slowly e.g. during
parturition.
 Hyperthermia means increased body temperature due to high environmental
temperature e.g. Pets in hot environment without water.
 Hyperpnoea: increased respiration
 Tachycardia: rapid heart beat
 Eupnea: true respiration
 Eucardia: true heart beat
 Degeneration: loss of muscle relaxation or decrease work load
 Hypothermia: decreased body temperature
 Atrophy: decrease in muscle mass
 Hypertrophy: increase in muscle mass.
1.3. Indicators of cell damage and types of necrosis
 1.3.1. Cell damage
Cell damage (also known as cell injury) is a variety of changes of stress that a cell suffers due
to external as well as internal environmental changes. Amongst other causes, this can be due
to physical, chemical, infectious, biological, nutritional or immunological factors. Cell
damage can be reversible or irreversible. Depending on the extent of injury, the cellular
response may be adaptive and where possible, homeostasis is restored. Cell death occurs when
the severity of the injury exceeds the cell's ability to repair itself. Cell death is relative to both
the length of exposure to a harmful stimulus and the severity of the damage caused. Cell death
may occur by necrosis or apoptosis.
Cellular death due to necrosis does not follow the apoptotic signal transduction pathway, but
rather various receptors are activated and result in the loss of cell membrane integrity and an
uncontrolled release of products of cell death into the extracellular space. This initiates in the
surrounding tissue an inflammatory response, which attracts leukocytes and nearby
phagocytes which eliminate the dead cells by phagocytosis. However, microbial damaging
substances released by leukocytes would create collateral damage to surrounding tissues. This
lead to the first indicator of cell damage which is morphology changes, degeneration,
Functional derangements and clinical significance and necrosis.
 Morphologic changes
The morphologic changes refer to the structural alterations in cells or tissues that occur
following the pathogenic mechanisms. The structural changes in the organ can be seen with
the naked eye or they may only be seen under the microscope. Those changes that can be seen
with the naked eye are called gross morphologic changes & those that are seen under the
microscope are called microscopic changes. Both the gross & the microscopic morphologic
changes may only be seen in that disease, i.e. they may be specific to that disease. Therefore,
such morphologic changes can be used by the pathologist to identify (i.e. to diagnose) the
disease. In addition, the morphologic changes will lead to functional alteration & to the
clinical signs & symptoms of the disease.

 Functional derangements and clinical significance

 The morphologic changes in the organ influence the normal function of the organ. By doing
so, they determine the clinical features (symptoms and signs), course, and prognosis of the
disease. In summary, pathology studies:- Etiology ⇨ Pathogenesis Morphologic changes ⇨
Clinical features & Prognosis of all diseases.

Understanding of the above core aspects of disease (i.e. understanding pathology) will help
one to understand how the clinical features of different diseases occur & how their treatments
work. This understanding will, in turn, enable health care workers to handle & help their
patients in a better & scientific way. It is for these reasons that the health science student
should study pathology. In addition, the pathologist can use the morphologic changes seen in
diseases to diagnose different diseases. There are different diagnostic modalities used in
pathology. Most of these diagnostic techniques are based on morphologic changes.

 Degeration

The normal cell is a highly complex unit in which the various organelles and enzyme systems
continuously carry out the metabolic activities that maintain cell viability and support its normal
functions. Normal function is dependent on:

 The immediate environment of the cell

 A continuous supply of nutrients such as oxygen, glucose, and amino acids; and
 Constant removal of the products of metabolism, including CO2.
Degeneration refers to the process by which tissue deteriorates and loses its functional ability due
to traumatic injury, aging and wear and tear.While degeneration affects all tissues of the body,
the natural degenerative process can particularly affect the vertebral discs and joints of the spine,
resulting in chronic back pain. Degeneration is reversible but may progress to necrosis if injury
persists. When it is associated with abnormal cell function, cell degeneration may also cause
clinical disease.

For example, the failure of the blood supply to an organ (ischaemia) due to thrombosis will
cause massive cell death due to lack of oxygen. A large area of cell death caused by ischaemia is
called an infarction. Another example of cell necrosis is seen in severe viral infections with
cytopathic viruses (e.g. rinderpest).

Notes
 Nonlethal Injury = Degeneration
 Programmed Cell Death = Apoptosis
 Lethal Injury = Necrosis
 Characterizations of Cell degeneration are:
 Abnormality of biochemical function,
 a recognizable structural change, or a combined biochemical and
 Structural abnormality.
 Types of necrosis
Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which
result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally
occurring programmed and targeted cause of cellular death. While apoptosis often provides
beneficial effects to the organism, necrosis is almost always detrimental and can be fatal. There
are different types of necrosis. The most known ones are the following.
 Coagulative necrosis

This is a type of accidental cell death typically caused by ischemia or infarction. In coagulative
necrosis, the architectures of dead tissue are preserved for at least a couple of days. It is believed
that the injury denatures structural proteins as well as lysosomal enzymes, thus blocking the
proteolysis of the damaged cells. The lack of lysosomal enzymes allows it to maintain a
"coagulated" morphology for some time. Like most types of necrosis, if enough viable cells are
present around the affected area, regeneration will usually occur. Coagulative necrosis occurs in
most bodily organs, excluding the brain. Different diseases are associated with coagulative
necrosis, including acute tubular necrosis and acute myocardial infarction.
 Fig1.1: coagulative necrosis
(https://upload.wikimedia.org/wikipedia/commons/3/3b/Histopathology_of_a_pheoch
romocytoma_with_coagula) (1/9/2022)

 Caseous necrosis:
Caseous necrosis or caseous degeneration is a unique form of cell death in which the tissue
maintains a cheese-like appearance. It is also a distinctive form of coagulative necrosis. The dead
tissue appears as a soft and white proteinaceous dead cell mass.

 Liquefactive necrosis
Liquefactive necrosis is characterized by digestion of tissue. It shows softening & liquefaction of
tissue. It characteristically results from ischemic injury to the CNS. It also occurs in suppurative
infections characterized by formation of pus.
 Fat necrosis
Fat necrosis can be caused by trauma to tissue with high fat content, such as the breast or it can
also be caused by acute hemorrhagic pancreatitis in which pancreatic enzymes diffuse into the
inflamed pancreatic tissue & digest it. The fatty acids released from the digestion form calcium
salts (soap formation or dystrophic calcification). In addition, the elastase enzymes digest the
blood vessels & cause the hemorrhage inside the pancreas, hence the name hemorrhagic
pancreatitis.
  Caseous nerosis
Caseous necrosis has a cheese-like (caseous, white) appearance to the naked eye. And it appears
as an amorphous eosinophilic material on microscopic examination. Caseous necrosis is typical
of tuberculosis.
 Gangrenous necrosis
This is due to vascular occlusion & most often affects the lower extremities & the bowel. It is
called wet gangrene if it is complicated by bacterial infection which leads to superimposed
liquefactive necrosis. Whereas it is called dry gangrene if there is only coagulative necrosis
without liquefactive necrosis.
 Gangrenous necrosis
This is due to vascular occlusion & most often affects the lower extremities & the bowel. It is
called wet gangrene if it is complicated by bacterial infection which leads to superimposed
liquefactive necrosis. Whereas it is called dry gangrene if there is only coagulative necrosis
without liquefactive necrosis

1.4. Gross pathological lesions

A gross pathological lesion is one that can be seen with the naked eye or any of various
pathological or traumatic changes in a bodily organ or tissue, including tumors, ulcers, sores, and
wounds. A microscopic or histologic lesion requires the magnification of a microscope to be
seen. The basis of sickle cell disease is a molecular lesion, one that is not even visible with a
microscope but is only detectable on the molecular (protein or DNA) level.
Gross pathological lesion can be described generally start with an overview of the location and
distribution of the lesion, then move on to the fine details of the lesion's size, shape, colour,
texture, etc. We usually describe the most important abnormalities first, and describe arte
factual changes last, if at all.
 Color
 Red – Hemorrhage, Congestion, Hemoglobin Staining (Imbibition)
 White – Mineral, Fat, Fibrous Tissue, Absence of Blood Flow, Necrosis
 Green – Bile Staining, Putrefaction, Eosinophilic Inflammation
 Yellow – Bilirubin (Icterus), Hematoidin (Erythrocyte Breakdown), Carotenoids
(High VitaminA Diet)
 Brown – Hemosiderin/Iron Deposition, Methemoglobin, Lipofuscin
  Consistency
 Soft – Necrosis, adipose tissue, lung
 Firm – Inflammation, fibrosis, cartilage
 Hard – Mineralization, bone
 Demarcation
 Well demarcated – vascular insult, benign tumor
 Poorly demarcated – inflammation, malignant
 Contour
 Sessile – having a broad base
 Pedunculated or polypoid – having a narrow base
 Shape
 Round – benign tumor, vascular (some organs), cystic lesion
 Rectangular or polygonal – vascular (some organs such as skin)
 Irregular – malignant tumor, inflammatory process
 Distribution
 Focal – primary tumor, traumatic injury, early stage of multifocal process
 Multifocal – hematogenous spread of infectious agent or neoplasm
 Multifocal to coalescing – Progression of multifocal lesion
 Locally extensive – Vascular insult, progression of focal lesion
 Diffuse – Metabolic, progression of multifocal or locally extensive lesion,
vascular insult.
 Fluid
 Watery – serum
 Viscous – contains mucous or fibrin
 Turbid – contains fibrin, inflammatory or neoplastic cells
 Opaque – contains cells or lipid droplets
Generally gross pathological lesions or changes that can be encountered during meat inspection
are the following
 Fever  Hemorrhage and Hematoma
 Septicemia  Bruises
 Pigmentation(melanosis, Icterus  Abscess
(Jaundice),  Emaciation
 Edema
  Emphysema  Shrinkage
 Calcification  Dislocation
 Abnormal odors
 Breakage
 Immaturity
 Swelling  Discharge

Gross pathological lesions are observed in both ante mortem and post mortem examination.,
1.4.1. Ante mortem examination
Conducting ante mortem procedures at the abattoir on the day of slaughter to identify and
condemn animals that are unfit for slaughter and to note clinical signs or lesions of disease that
may not be apparent after slaughter.
Diseases lesions or changes detected during ante mortem examination are the following.
 Fever (Pyrexia)

Fever is an abnormal elevated body temperature. It may be classified as septic and

aseptic according to the presence or no presence of an infection. In septic fever the
infection is caused by viruses, bacteria, bacterial toxins, protozoa and fungi.
 Septicemia
Known at ante mortem examination by Congestion or Petechial hemorrhages of conjunctivae,
mouth and vulvar mucosa.
 Bruises
Bruises are frequently found on antemortem and post-mortem examination in
food producing animals and poultry. In cattle bruises caused by transportation or
handling are commonly found in the hip, chest and shoulder areas; in pigs within the
ham and in sheep in the hind leg. Bruises and hemorrhage in the hip joint are caused
by rough handling of animals during shackling. Bruises in poultry can be localized
or generalized and are frequently associated with bone fractures or ruptured
ligament tendons.

Fig1.2, Extensive bruises of a beef carcass

  Emaciation

Emaciation is a common condition of food animals and is characterized by a loss of fat and flesh
following the loss of appetite, starvation and cachexia.

Fig1.3: Emaciated cow showing marked reduction of muscle mass.

 Edema

Edema is the accumulation of excess fluid in the intercellular (interstitial) tissue compartments, including
body cavities.

Fig.1.4: Ventral edema.

(https://www.researchgate.net/figure/Ventral-edema-and-jugular-venous-distention-in-a-Jersey-
cross-bred-cow-with-pericarditis_fig1_51102772) 1/9/2022

 Immaturity
Immaturity occurs mainly in calves. The slaughter of calves younger than two weeks of age is
prohibited.
1.4.2. Post mortem examination

Post mortem examination are conducted for the purpose of identifying the cause of a disease and
for wholesome meat consumption of meat for public. The most encountered gross pathological
lesions during post mortem examination are the following.
 Pigmentations
 Melanosis

Melanosis is is a pigmentation and it is observed in ante mortem and post mortem examination.it
is an accumulation of melanin in various organs including the kidneys, heart, lungs and liver and
other locations such as brain membranes, spinal cord, connective tissue, periosteum etc. Melanin
is an endogenous brown-black pigment randomly distributed in tissue.

Fig1.5: Melanin deposits in the sheep viscera

 Icterus (Jaundice)

Icterus is the result of an abnormal accumulation of bile pigment, bilirubin, or hemoglobin in the
blood. Yellow pigmentation is observed in the skin, internal organs, sclera (the white of the eye),
tendons, cartilage, arteries, joint surfaces etc.
Fig.1.6: Jaundice of an aged cow caused by liver disease. Note yellow discoloration of body
fat, lungs, heart and kidneys (https://www.google.com/search?
hl=en&tbm=isch&oq=&aqs=&q=-%09Icterus+%28Jaundice%29} 1/9/2022

 Hemorrhage and Hematoma

Hemorrhage is seen at slaughter in various organs, mucous and serous membranes, skin,
subcutaneous tissue and muscles. It may be caused by trauma, acute infectious diseases or
septicemia.

Fig. 1.7: Fractured bone and muscle hemorrhage in a market hog.

 Abscess
An abscess is a localized collection of pus separated from the surrounding tissue by a fibrous
capsule.

Fig 1.8: Liver abscesses caused by Fusobacterium necrophorum.

 Emphysema
Emphysema in animals is associated with some disease conditions and is caused by an
obstruction to the outflow of a air or by extensive gasping respiration during slaughter
procedures.
  Calcification
Calcification is the deposition of calcium salts in dead and degenerating tissue. It may be
regarded as a body reaction to immobilize some foreign agents.

Fig1.9: Parasitic lesions undergoing mineralization in a sheep liver

 Abnormal odors
Abnormal odors may result from the ingestion of certain feedstuff, drugs, various pathological
conditions, absorption of odors from strong smelling substances and sexual odor from some male
animals.
 Tumor and neoplasm
A tumour is an abnormal mass of tissue which grows without control and uncoordinated with the
tissue or organs of origin or those nearby. Its presence if often cumbersome to the tissue or organ
it arose either by pressure or by replacement of normal functional tissue. Tumour cells resemble
healthy cells however serve no useful purpose. The term tumour in current medical lexicon is
presently limited to neoplastic growths.
 Wound
Wounds are cuts, tears, burns, breaks, or other damage to living tissue. Wounds are often
classified as clean, contaminated, or infected. Clean wounds are those created under sterile
conditions, such as surgical incisions. The number of bacteria present determines the difference
between contaminated and infected wounds.

 Shrinkage
Tissue shrink is the loss of fluid from body tissues. This occurs when cattle go long periods
without feed and water and are then subjected to other types of stress. Stress can be caused by
events such as long distance trucking or rough handling. Tissue shrink occurs when cattle
experience over 6% weight loss.

 Breakage
It is a soft tissue injury at the damage of muscles, ligaments and tendons throughout the body.
Common soft tissue injuries usually occur from a sprain, strain, a one-off blow resulting in a
contusion or overuse of a particular part of the body.

 Discharge
Any pathological fluid come out of the damage tissue or the injured tissue to the extra cellular
content or it may liquefy to the external environment.

 Dislocation
Dislocation is a condition that happens when the bones of a joint are knocked out of place. A
joint can be partially dislocated (subluxation) or fully dislocated. A dislocation can be caused by
a trauma (car accident or fall) or the weakening of muscles and tendons. A dislocated joint can
be treated through medication, manipulation, rest or surgery.

Dislocations can be very painful and cause the affected joint area to be unsteady or immobile
(unable to move). They can also strain or tear the surrounding muscles, nerves, and tendons
(tissue that connects the bones at a joint). You should seek medical treatment for a dislocation.

LO#2- Identify inflammatory reactions and exudates

2.1 Inflammatory reactions and cardinal signs

2.1.1. Inflammatory reaction

Inflammatory reaction or response: is a defence mechanism that evolved in higher
organisms to protect them from infection and injury. Its purpose is to localize and
eliminate the injurious agent and to remove damaged tissue components so that the body
can begin to heal. The response consists of changes in blood flow, an increase in
permeability of blood vessels, and the migration of fluid, proteins, and white blood cells
(leukocytes) from the circulation to the site of tissue damage.
The inflammatory response (inflammation) occurs when tissues are injured by bacteria,
trauma, toxins, heat, or any other cause. The damaged cells release chemicals including
histamine, bradykinin, and prostaglandins. These chemicals cause blood vessels to leak
fluid into the tissues, causing swelling. Inflammation is a complex process of vascular
and cellular alterations occurs in body in response to injury. The term inflammation has
been derived from a Latin word inflammare, means to ‘set on fire’.
The inflammation is considered as an important event in body for implementation of
existing defence mechanisms in circulating blood to dilute, naturalize or kill the irritant
causative agent. Thus, it is said that the immunity is the resistance of body, while
inflammation is the implementation of that immunity. It is beneficial to body except
chronic persistent and immune origin. Inflammation starts with sub- lethal injury and
ends with healing.
Since the inflammatory reaction are occur when the cells are injured , it is better to
explain the cause of cell injury .

2.1.2. Etiology of cell injury:

 Genetic causes
 Developmental defects: Errors in morphogenesis
 Cytogenetic (Karyotypic) defects: chromosomal abnormalities
 Single-gene defects: Mendelian disorders
 Multifactorial inheritance disorders.

 Acquired causes
 Hypoxia and ischemia
 Ischemia (loss of blood supply).
 Inadequate oxygenation (cardio respiratory failure).
 Loss of oxygen carrying capacity of the blood (anemia or CO poisoning).
 Physical agents
 Trauma
 Heat
 Cold
 Radiation
 Electric shock
 Chemical agents and drugs
 Endogenous products: urea, glucose
 Exogenous agents
 Therapeutic drugs: hormones
 Nontherapeutic agents: lead or alcohol
 Microbial agents
 Viruses
 Rickettsiae
 Bacteria
 Fungi
 Parasites
 Immunologic agents
 The immune process is normally protective but in certain circumstances the
reaction may become deranged.
 Hypersensitivity to various substances can lead to anaphylaxis or to more
localized lesions such as asthma.
 In other circumstances the immune process may act against the body cells –
autoimmunity.
 Nutritional derangements
 Protein-calorie deficiencies are the most examples of nutrition deficiencies.
 Vitamins deficiency.
 Excess in nutrition are important causes of morbidity and mortality.
 Excess calories and diet rich in animal fat are now strongly implicated in the
development of atherosclerosis.
  Obesity alone leads to an increased vulnerability to certain disorders, such as
atherosclerosis, coronary heart disease, diabetes mellitus.
 Aging
 Programmed aging whereby after a defined number of divisions the cell
undergoes terminal differentiation.
 Development of an increasing population of cells irreversibly committed to
senescence and death.
 Psychogenic diseases
 Iatrogenic factors
 Idiopathic diseases.

2.1.3. The cardinal sign

Inflammation is response triggered by damage to living tissue. Inflammation is a local response
to cellular injury that is marked by capillary dilatation, leukocytic infiltration, redness, heat, and
pain and that serves as a mechanism initiating the elimination of noxious agents and of damaged
tissue. Based on this pathogenesis mechanism to the initiation of cell injury: There are five
cardinal signs of inflammation, though it may also cause additional symptoms if severe.

a. Pain: An unpleasant sensation that can range from mild, localized discomfort to agony.
Pain has both physical and emotional components. The physical part of pain results from
nerve stimulation. Pain may be contained to a discrete area, as in an injury, or it can be
more diffuse, as in disorders like fibromyalgia.
b. Redness: Erythema (from the Greek erythros, meaning red) is redness of the skin or
mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries.
It occurs with any skin injury, infection, or inflammation.
c. Swelling: is an increase in the size or a change in the shape of an area of the body.
Swelling can be caused by collection of body fluid, tissue growth, or abnormal movement
or position of tissue.
d. Hotness: ischaracterized by high temperature. Being at or exhibiting a temperature that is
higher than normal or desirable: a hot forehead.
e. Loss of function: A mutation that results in reduced or abolished muscle (protein)
function. Muscle function loss is when a muscle does not work or move normally. The
 medical term for complete loss of muscle function is paralysis.

Fig2.1: The cardinal signs of inflammation include: pain, heat, redness, swelling, and loss
of function. Some of these indicators can be seen here due to an allergic reaction
(https://en.wikipedia.org/wiki/Inflammation#Causes), (1/92022)

2.2. Mediators and actors of inflammation

The mediators and actors of inflammation are those functional participants of body systems
to the protective response involving immune cells, blood vessels, and molecular mediators to
eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the
original insult and the inflammatory process, and initiate tissue repair. These activator and
mediators are involved in the different phase of inflammatory response which includes
histamine, cytokines, complements, interleukin (mediators) and, neutrophils, macrophages,
monocytes and B-cell as actors of inflammation.

Inflammation can be classified as either acute or chronic. Acute inflammation is the initial
response of the body to harmful stimuli, and is achieved by the increased movement of
plasma and leukocytes (in particular granulocytes) from the blood into the injured tissues. A
series of biochemical events propagates and matures the inflammatory response, involving
the local vascular system, the immune system, and various cells within the injured tissue.
Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the
type of cells present at the site of inflammation, such as mononuclear cells, and is
characterized by simultaneous destruction and healing of the tissue from the inflammatory
process.
2.3. Types and consequence of inflammation

2.3.1. Phase of inflammation

 Acute phase of inflammation
Acute inflammation occurs immediately upon injury, lasting only a few days. Cytokines and
chemokines promote the migration of neutrophils and macrophages to the site of inflammation.
Pathogens, allergens, toxins, burns, and frostbite are some of the typical causes of acute
inflammation. Toll-like receptors (TLRs) recognize microbial pathogens. Acute inflammation
can be a defensive mechanism to protect tissues against injury. Inflammation lasting 2–6 weeks
is designated sub-acute inflammation.

Acute inflammation is the early (almost immediate) response of a tissue to injury. It is

nonspecific and may be evoked by any injury short of one that is immediately lethal. Acute
inflammation may be regarded as the first line of defense against injury and is characterized by
changes in the microcirculation: exudation of fluid and emigration of leukocytes from blood
vessels to the area of injury. Acute inflammation is typically of short duration, occurring before
the immune response becomes established, and it is aimed primarily at removing the injurious
agent.Phases of acute inflammation may include
 Vascular phase
In the vascular phase, small blood vessels adjacent to the injury dilate (vasodilatation) and blood
flow to the area increases. The endothelial cells initially swell, then contract to increase the space
between them, thereby increasing the permeability of the vascular barrier. This process is
regulated by chemical mediators.

Exudation of fluid leads to a net loss of fluid from the vascular space into the interstitial space,
resulting in oedema (tumour). The formation of increased tissue fluid acts as a medium for which
inflammatory proteins (such as complement and immunoglobulins) can migrate through. It may
also help to remove pathogens and cell debris in the area through lymphatic drainage.

 Exudative phase
Exudative phase indicates significant alteration in the normal permeability of the small blood
vessels in the region of injury. The two components of exudate, fluid and protein, serve good
purposes.They are attracted to the site of injury by the presence of chemotaxins, the mediators
released into the blood immediately after the insult.
 Margination: cells line up against the endothelium
 Rolling: close contact with and roll along the endothelium
 Adhesion: connecting to the endothelial wall
 Emigration: cells move through the vessel wall to the affected area

 Cellular phase
The cellular stage of acute inflammation is marked by changes in the endothelial cells lining the
vasculature and movement of phagocytic leukocytes into the area of injury or infection.The most
important feature of inflammation is the accumulation of white blood cells at the site of injury.
Most of these cells are phagocytes, certain “cell-eating” leukocytes that ingest bacteria and other
foreign particles and also clean up cellular debris caused by the injury. The main phagocytes
involved in acute inflammation are the neutrophils, a type of white blood cell that contains
granules of cell-destroying enzymes and proteins. Outcomes cellular phase results are:

 Complete resolution – with total repair and destruction of the insult

 Fibrosis and scar formation – occurs in cases of significant inflammation
 Chronic inflammation – from a persisting insult
 Formation of an abscess
 Inflammatory exudates of acute inflammation
The main characteristics of acute inflammation are the exudation of fluid and plasma proteins
(edema) and the emigration of leukocytes (predominantly neutrophils). Neutrophils and other
motile white cells emigrate or move from the blood vessels to the perivascular tissues and the
injury (implant) site.
a. “Exudate” is fluid buildup caused by tissue leakage due to inflammation or local cellular
damage.
b. “Transudate” is fluid buildup caused by systemic conditions that alter the pressure in blood
vessels, causing fluid to leave the vascular system.

 The fluid is exudate if one of the following Light’s criteria is present:

  Effusion protein/serum protein ratio greater than 0.5
 Effusion lactate dehydrogenase (LDH)/serum LDH ratio greater than 0.6
 Effusion LDH level greater than two-thirds the upper limit of the laboratory's reference
range of serum LDH.

Lactate dehydrogenase (LDH) is an enzyme normally inside of cells in the body. When there is
damage to cells, LDH leaks out and becomes part of the effusion. Measuring a high LDH in the
effusion is indicative of cell damage, which typically comes from an exudative process. This is
why one of Light’s criteria measures LDH in the effusion.
 Causes of Transudative cells

 Partially collapsed lung tissue (atelectasis): Due to increased negative pressure inside the
lung cavity
 Cerebrospinal fluid (CSF) leak into lung cavity (pleural space): Thoracic spine injury,
ventriculo peritoneal (VP) shunt dysfunction

 Heart failure
 Liver dysfunction
 Lowbloodalbumin (hypoalbuminemia)
 Iatrogenic (misplaced catheter into lung)
 Nephrotic syndrome
 Peritoneal dialysis

 Blockage of urinary system causing urine backup in the body (urinothorax due to
obstructive uropathy)

 Causes of Oxidative Effusions

 Abdominal fluid: Abscess in tissues near lung, fluid in the abdomen (ascites),
Meigs syndrome, pancreatitis
 Connective tissue disease:churg-strauss disease, lupus, rheumatoid arthritis,
Wegener granulomatosis.
 Endocrine: Low thyroid (hypothyroidism), ovarian hyperstimulation.
 Iatrogenic: Drug-induced, esophageal perforation, feeding tube in lung
  Infectious: Abscess in tissues near lung, bacterial pneumonia, fungal disease,
parasites, tuberculosis
 Inflammatory: Acute respiratory distress syndrome (ARDS), asbestosis,
pancreatitis, radiation, sarcoidosis, high levels of urea in the blood (uremia)
 Lymphatic abnormalities: Chylothorax (fluid around the lungs), cancer in
the lymph nodes, lymphangiectasia (over-dilation of lymph vessels)
 Malignancy: Cancer, lymphoma, leukemia, mesothelioma, paraproteinemia
The process of acute inflammation is initiated by resident immune cells already present in the
involved tissue, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mast
cells. These cells possess surface receptors known as pattern recognition receptors (PRRs),
which recognize (i.e., bind) two subclasses of molecules: pathogen-associated molecular patterns
(PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs are compounds that are
associated with various pathogens, but which are distinguishable from host molecules. DAMPs
are compounds that are associated with host-related injury and cell damage.

At the onset of an infection, burn, or other injuries, these cells undergo activation (one of the
PRRs recognizes a PAMP or DAMP) and release inflammatory mediators responsible for the
clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the
redness (rubor) and increased heat (calor). Increased permeability of the blood vessels results in
an exudation (leakage) of plasma proteins and fluid into the tissue (edema), which manifests
itself as swelling (tumor). Some of the released mediators such as bradykinin increase the
sensitivity to pain (hyperalgesia, dolor). The mediator molecules also alter the blood vessels to
permit the migration of leukocytes, mainly neutrophils and macrophages, to flow out of the
blood vessels (extravasation) and into the tissue. The neutrophils migrate along a chemotactic
gradient created by the local cells to reach the site of injury. The loss of function (functio laesa)
is probably the result of a neurological reflex in response to pain.

In addition to cell-derived mediators, several acellular biochemical cascade systems—consisting

of preformed plasma proteins—act in parallel to initiate and propagate the inflammatory
response. These include the complement system activated by bacteria and the coagulation and
fibrinolysis systems activated by necrosis (e.g., burn, trauma).
Acute inflammation may be regarded as the first line of defense against injury. Acute
inflammatory response requires constant stimulation to be sustained. Inflammatory mediators are
short-lived and are quickly degraded in the tissue. Hence, acute inflammation begins to cease
once the stimulus has been removed.

Diagram 2.1: A flowchart depicting the events of acute (inflammation

(https://en.wikipedia.org/wiki/Inflammation#Types), (1/92022)

 Chronic phase of inflammation

Chronic inflammation is inflammation that lasts for months or years. Macrophages, lymphocytes,
and plasma cells predominate in chronic inflammation, in contrast to the neutrophils that
predominate in acute inflammation. Diabetes, cardiovascular disease, allergies, and chronic
obstructive pulmonary disease (COPD) are examples of diseases mediated by chronic
inflammation. Obesity, smoking, stress and insufficient diet are some of the factors that promote
chronic inflammation.[9] A 2014 study reported that 60% of Americans had at least one chronic
inflammatory condition, and 42% had more than one.
 Chronic inflammation is the response of tissue against injurious agent that persists for a long
time. The tissue affected by chronic inflammation usually show immune response,
phagocytosis, necrosis and repair. Chronic inflammatory process is usually productive or
proliferative rather than exudative.
 Causes
Chronic inflammation usually develops following acute inflammation due to persistence of
infection. Chronic inflammation usually follows repeated acute inflammation Moreover, It may
be primary develop due to a low grade of tissue response to persist infection with intracellular
microorganisms as Mycobacterium tuberculosis, prolonged exposure to non-degradable but
potent toxic substance as silicosis and immune reaction as type IV hypersensitivity.
The affected tissue in chronic inflammation usually shows the following characters, Immune
response represented by plasma cells, lymphocytes and macrophages. Moreover, phagocytosis,
necrosis and repair, which characterized by presence of newly, formed capillary and fibrous
tissue proliferation and collagen fiber deposition.
 Microscopic picture
The characteristic feature of chronic inflammation is infiltration of tissue with mononuclear cells
specially macrophages, lymphocytes and plasma cells besides newly develop blood vessels,
fibroblast proliferation and collagen fibre deposition.
 Gross appearance
Chronic inflammation is characterized by absence of cardinal signs of inflammation. The
inflammatory area is indurated and grayish white in color. Moreover the inflammation may be
not noticed. Granulomatous inflammation Granulomatous inflammation is a special kind of
chronic inflammation, which occurs in the presence of indigestible material and/or cell-mediated
immunity. Moreover, granulomatous inflammation is a type of chronic inflammation
characterized by presence of granuloma. Granuloma composed of closely packed collection of
cells or sheets of predominantly macrophages. Macrophage in granuloma usually activated
(epithelioid cells). Besides macrophages, granulomatous inflammation shows lymphocytes,
plasma cells, giant cells and sometimes neutrophils. The classic granulomatous diseases include
tuberculosis, leprosy, foreign body reactions, including the reactions to everything from sutures
to schistosome eggs.
 Fig2.2: Chronic inflammation of tongue, liver and lung

(https://www.google.com/search?
hl=en&tbm=isch&oq=&aqs=&q=Chronic+inflammation+of+tongue%2C+liver+and+lung
%2Canimal) 1/9/2022

2.3.2. Consecounse of inflammation

The consequence of inflammation is ended by the process of tissue repair and wound healing
 Introduction Tissue Repair and Healing
Wound Healing: Healing is the body response to injury in an attempt to restore normal structure
and function. Two Distinct processes
i. Regeneration: - Complete restoration of the original tissues.
ii. Repair: - When the healing takes place by proliferation of connective tissue element
resulting in fibrosis and scarring.
A. Healing (Tissue Repair)
 Tissue: Proliferating potential of cell types
 Labile cells - Continuously dividing cells. E.g. epidermis, epithelial cells, bone marrow cells.
 Stable cells
  Quiescent cells
 Undergoes division occasionally
 Liver, kidney pancreas, fibroblasts, endothelial cells
 Permanent cells
 Non–dividing cells
 Neurons, muscle cells (cardiac, skeletal)
Hence, healing occurs Depending on the proliferation potential of the cells as described above by
a. Healing by regeneration
b. Healing by substitution
Wound healing is not a separate process and occurs along with the inflammatory reaction. It is a
complex but orderly phenomenon involving a number of processes.Namely,
 Acute inflammatory reaction following initial injury.
 Parenchymatous cellular regeneration
 Migration and production of parenchymatous and connective tissue cell
 Extracellular matrix, protein synthesis
 Remodelling of connective tissue
a. Healing by primary union or first intention (regeneration)
 This type of healing occurs in clean surgical approximated incision i.e. limited bleeding and
tissue destruction.
 The sequence of events occurring in primary union is given below
0 hrs Clot filling the incised area
3-24hrs. Neutrophilic infiltration
48 hrs Basal cell proliferation and epithelial closure takes place by 24-48 hours
72 hrs Macrophages replace neutrophils. Granulation tissue begins to appear. Collagen is
arranged vertically
120 hrs Incised space is filled with granulation tissue. Neovascularisation is maximal. Collagen
fibre begin to appear and epithelial proliferation is maximal
2 weeks Proliferation of fibroblast with continuous collagen accumulation producing a scar.
Type III collagen is deposited early in scar tissue and is replaced by adult type I
collagen which accounts for wound strength. Newly formed blood vessels disappear.

8 week Scar tissue consists of granulation tissue which is devoid of inflammation covering
 intact epidermis.

b. Healing by second intention (substitution)

The wound involved shows extensive loss of cells and tissue. E.g. infarction, ulceration,
abscesses, surface wound with large defects. The wound is filled with tissue debris, a few
erythrocytes and bacteria. Abundant granulation tissue (soft, pink, granular appearance of wound
surfaces) grows in from the margin to fill the defect but at the same time the wound contracts
i.e., the defect is marked by depression and decrease from its original size. Microscopically
granulation tissue consists of new capillaries, fibroblasts, collagen and proteoglycan rich ground
substance. Initially granulation tissue is soft and spongy due to leaky blood vessels
Injury – open wound – excess loss of tissue – infected – necrosis – inflammation
↓
Blood clot
↓
24 hours – neutrophils infiltrate to destroy irritant
↓
48-72 hours – macrophages and lymphocytes infiltrate
↓
Removal of necrotic and cellular debris by liquefaction by macrophages
↓
Red granules from underneath (granulation tissue) represent proliferating capillaries. Fibroblast
also proliferate to fill the gap
↓
There is a definite order.
Base - capillaries grow vertically and project towards the surface. Fibroblast grows perpendicular
to capillary and parallel to surface – pulling pressure of the wound
↓
Surface – fibroblasts are arranged parallel to capillaries exerting tension towards wound surface
for easy closure. This arrangement differentiates granulation tissue from fibrosarcoma which
lacks orderly arrangement.
↓
The surface is closed by the epithelium proliferating from the margin
↓
 The tissue is devoid of sweat gland, sebaceous gland, hair and hair follicles and pigment. So, the
scar appears dry and un pigmented white and puckered as it becomes avascular and shrinkage of
collagen.
Exuberant granulation or proud flesh
Sometimes the granulation continues to grow in abnormally large amount due to irritant,
movement or trauma which prevents healing. This condition is called proud flesh or excess
granulation tissue.
Keloid
 Keloid is another condition. Reason for its development is not known. The connective tissue
below the epithelial covering continues to proliferate. This condition may recur after the
removal. This is found in horses and black people having some genetic or familial predisposition.

Systemic and local factors influencing wound healing

Systemic factors
 Nutritional
 Vitamins – vitamin C is required for collagen synthesis.
 Proteins deficiency – starvation.
 Sulphur containing amino acids (methionine and cystine) are important and required
for intermediate forms of collagen.
 Zinc – as metalloenzyme, it is essential for remodelling of extracellular matrix
 Metabolic factors
 Diabetes mellitus – delays healing.
 Hyperadrenocortism
 Circulatory stasis or adequacy of blood supply
 Inadequate blood supply – delays healing
 Hormones: concurrent glucocorticoid therapy hinders inflammatory and reparatory process
Local factors
 Infection can delay healing
 Mechanical – movements directly affect wound healing
 Foreign bodies impede healing
 Size, location and type of wound
 Cold inhibits wound healing
Others
 Old age-Healing is slower than young ones.
 Chemotherapeutic agents
 Radiation
 Immunodeficiency

2.4. Clinically important Inflammatory lesions

Inflammatory cells are a source of cytokines and growth factors that may target the endothelial
cells and contribute to the development of structural and functional abnormalities of the vessel
wall. Inflammatory lesions in acne include small red bumps (papules), pustules, large red bumps
(nodules) and pseudocysts (these are fluctuant nodules). Inflammatory acne lesions are often
painful. The most known and clinically important inflammatory lesions are the following.

 Macule: Macules are circumscribed alterations in skin color. The skin surface is either
elevated or depressed in relation to the surrounding skin. Macules may be of any size or
color.
 Papule: Papule is a solid, elevated lesion with no visible fluid which may be up to ½ cm.
in diameter. The elevation may be accounted for by metabolic deposits, infiltrates, or
hyperplasia of cellular elements, etc. A papulosquamous lesion is a papule with
desquamation (scaling).
 Nodules: Nodules are forms of papules, but are larger and deeper. They may be located
in the dermis or subcutaneous tissue, or in the epidermis. Nodules are usually ½ cm. or
more in diameter. Ex: Metastatic neoplasm; xanthoma
 Plaque: An elevated area of skin 2 cm. or more in diameter. It may be formed by a
coalescence of papules or nodules. The surface area is greater than its height. It is a plate-
like lesion.
 Wheal: A wheal is an evanescent rounded or flat-topped elevation in the skin that is
edematous, and often erythematous. They may vary in size from a few mm. to many cm.
The shape may change and these lesions are usually pruritic (itchy). These are really
variations of papules, nodules or plaques that are evanescent.
 Vesicles and Bullae: (Blisters) Vesicles are circumscribed epidermal elevations in the
skin containing clear fluid and less than ½ cm. in diameter. If the lesion has a diameter of
greater than ½ cm, it is called a bulla. Vesicles and bullae arise from a cleavage at various
levels of the skin. The more superficial the location, the more flaccid the bullous lesion.
Vesicles and bullae are commonly called blisters. It is the diameter, not the cleavage
plane that differentiates vesicles and bullae.
 Pustule: A pustule is a circumscribed elevation of the skin that contains a purulent
exudate that may be white, yellow, or greenish-yellow in color.
 Abscess: A localized collection of pus in a cavity formed by disintegration or necrosis of
tissue.
 Cyst: A cyst is a closed sac that contains liquid or semisolid material. On palpation a cyst
is usually resilient.
 Atrophy: Atrophy of the skin may involve the epidermis, or the dermis, or both. It is the
thinning process associated with decreased number of cutaneous cells. Sometimes the
normal skin markings may be lost. Dermal atrophy may give rise to a depression in the
skin. Stria (plural striae) is linear, atrophic, pink, purple, or white lesions of the skin and
is sometimes called “stretch marks”.
 Sclerosis: Sclerosis refers to a circumscribed, diffuse hardening or induration in the skin.
It is usually produced by induration of the dermis and/or subcutaneous tissue. Palpation is
often necessary in diagnosing sclerosis.
 Erosion: A loss of epidermis.
 Ulcer: A loss of epidermis and dermis (and sometimes deeper tissue). If erosions and/or
ulcers are produced by scratching, the term excoriation is used.
 Scar: Scars occur whenever ulceration has taken place and they reflect the pattern of
healing. They may be hypertrophic, atrophic, or cribriform (perforated with multiple
small pits).
 Crusts (scabs): Crusts result when serum, blood, or purulent exudate dries and it is a
hallmark of pyogenic infection. Crusts are yellow when they have arisen from dried
serum; green or yellow-green when formed from purulent exudate; and brown or dark red
when formed from blood.
 Lichenification: A chronic thickening of the epidermis with exaggeration of its normal
markings, often as a result of scratching or rubbing.
  Acne: presents primarily as papules but can also cause pustules, nodules, or cysts. It is
most common on the face, neck, chest, and upper back and can leave scars if not treated
 Keratitis: is caused by exposure to sunlight (ultraviolet radiation) and appears as thick,
scaly crusts on the skin.
 Blisters: a small bubble on the skin filled with serum and caused by friction, burning, or
other damage.
 Cellulitis: a lesion caused by agents that affected skin appears swollen and red and may
be hot and tender. Without treatment with an antibiotic, cellulitis can be life-threatening.
 Sore: physically painful or sensitive, as a wound, hurt, or diseased part: a sore arm.
Suffering bodily pain from wounds, bruises, etc., as a person: He is sore because of all
that exercise. Suffering mental pain; grieved, distressed, or sorrowful: to be sore at heart.
 Dermatitis: is a general term that describes a common skin irritation. It has many causes
and forms and usually involves itchy, dry skin or a rash. Or it might cause the skin to
blister, ooze, and crust or flake off.
 Enzema: a particular type of inflammatory reaction of the skin in which there is
erythema (reddening), edema (swelling), papules (bumps), and crusting of the skin
followed, finally, by lichenification (thickening) and scaling of the skin.
 Utricaria: is a unique dermatologic disorder caused by infiltration of mast cells in the
skin and has pathology distinct from common urticaria but can present with urticarial
lesions associated with blisters.
 Scabies: is an itchy skin condition caused by a tiny burrowing mite called
Sarcoptesscabiei. Intense itching occurs in the area where the mite burrows.
 Cyst: is caused by an infestation of the skin by the human itch mite (Sarcoptesscabiei var.
hominis). The microscopic scabies mite burrows into the upper layer of the skin where it
lives and lays its eggs. The most common symptoms of scabies are intense itching and a
pimple-like skin rash.
The shape, size, color and texture of the primary lesion as well as any symptoms that may or may
not be present are important in describing skin lesions. The arrangements of lesions in relation to
one another as well as their distribution over the body are also important in fully describing a
dermatosis. The following terms may apply to the shape or arrangement of skin lesions: linear,
annular, polycyclic; aciform; serpiginous; grouped (herpetiform and zosteriform); agminate
(collected together into clusters or masses); reticular (netlike). The following terms are helpful in
describing the distribution of skin lesions: generalized; localized; bilateral; unilateral;
symmetrical; asymmetrical; sun-exposed; intertriginous.
Miscellaneous:
• Pruritus = itching
• Pruritic = itchy
• Erythema = redness of the skin produced by vascular congestion or increased perfusion.
 Figure 2. 3: Cyst, Blister and Acne types of lesions

2.5. Development of oedema, abscess and respiratory discharges

2.5.1. Introduction To Oedema

 Oedema denotes abnormal accumulation of fluid in the interstitial tissue spaces and body
cavities.
 There is always certain amount of fluid in these structures, but any excess is removed by the
lymphatics as lymph.
 In health condition there is a constant passage of fluid from the capillaries to the tissues
and vice versa, and the chief factors concerned in the process are hydrostatic (capillary
blood-pressure) and osmotic pressure of the protein.
 At the arterial end of capillaries blood pressure exceeds osmotic pressure of the blood and
fluid diffuses to the tissue spaces.
 At the venous end of capillaries osmotic pressure of blood increases owing to increased
concentration of colloids, whereas, blood pressure falls hence facilitating re-absorption of
fluid.
 If the hydrostatic or osmotic balances in the blood vessels and tissues are impaired or the
permeability of capillaries is increased oedema would develop.
2.5.2. Factors concerned with production of oedema:
 Increased capillary blood pressure (hydrostatic pressure)
 Decreased colloid osmotic pressure of blood plasma
 Increased permeability of capillary wall
 Increased colloid osmotic pressure of the tissue
 Lymphatic obstruction- only causes local oedema
NB: colloid osmotic balance of blood is controlled by a protein called albumin. Damage to the
liver, which is responsible for the synthesis of albumin, would lead to oedema.

2.5.3. Fluid nature of oedema:

 Oedematous fluid is transudate.
 Resembles plasma and has pale or straw-colour
 It is watery, but contains protein and has lower specific gravity
 It does not clot in any way

2.5.4. Structural changes due to oedema:

When subcutaneous tissues are involved:
 Puffy swelling that pits on pressure
 Freely moving fluid that oozes on cutting
 Generalized subcutaneous oedema is called anasarca.
In the involvement of serous cavities:
 Ascites- fluid in the peritoneum
 Hydro pericardium- fluid in the pericardium
 Hydrothorax- fluid in the thoracic cavity

2.5.5. Types of oedema

  Renal oedema- renal diseases may lead to filtration of protein from glomeruli leading
to hypoproteinaemia hence causing oedema.
 Parasitic oedema – this develops due to blood sucking parasites like Hemonchus in
sheep. In cases of hemonchosis fluid accumulates under the lower jaw known as bottle-
jaw/submandibular oedema due to lowering of the neck during grazing.
 Nutritional oedema- mal-nutrition leads to hypoproteinaemia.
 Liver diseases- albumin and other proteins are synthesised in the liver. Any disease in
the liver may interfere with albumin synthesis
 Cardiac oedema- this is due to lack of increased hydrostatic pressure. E.g. heart failure
(congestion)
 Inflammatory oedema- there histamine production in inflammation. Histamine causes
dilatation of vessel wall leading to leakage of fluid and colloid.
2.5.6. Outcome of oedema:
 Recovery if the cause is removed
 Inflammation due to bacterial infection
 Death due to:
 Pressure of accumulating fluid
 Inability of vital organs to function. E.g. oedema of lungs that fills the alveoli with
fluid
 Asphyxia- oedema of larynx.

2.5.7. Abscess

Abscess is defined as Symptom consisting of a localized collection of pus surrounded by

inflamed tissue. It is a tender mass generally surrounded by a colored area from pink to deep red.
Abscesses are often easy to feel by touching. The vast majority of them are caused by infections.
Inside, they are full of pus, bacteria and debris. It is Painful and warm to touch, abscesses can
show up any place on the animal body. The most common sites on the skin, areas around the
anus and vagina, feet’s, around a tooth (dental abscess), and in groin. Inflammation around a hair
follicle can also lead to the formation of an abscess, which is called a boil (furuncle)
 Abscess Causes
When normal skin barrier is broken, even from minor trauma, or small tears, or inflammation,
bacteria can enter the skin. An abscess can form as the body's defences try to kill these germs
with inflammatory response (white blood cells = pus). Obstruction in a sweat or oil (sebaceous)
gland, or a hair follicle or a pre-existing cyst can also trigger an abscess. The middle of the
abscess liquefies and contains dead cells, bacteria, and other debris. This area begins to grow,
creating tension under the skin and further inflammation of the surrounding tissues. Pressure and
inflammation cause the pain.

2.5.8. Respiratory discharge

It is a clinical manifestation of respiratory disease expressed in nasal discharge. Nasal discharge
may be serous, catarrhal, purulent, or haemorrhagic, depending on the extent of mucosal or
turbinate damage. It indicates increased production of normal secretions, sometimes
supplemented by neutrophils (purulent) or blood (haemorrhage). It probably also indicates
decreased “grooming” of the nostrils with the tongue when animals are ill. Epistaxis (bleeding
from the nose) is often caused by vascular rupture, such as in mycotic infection of the guttural
pouch or exercise-induced pulmonary hemorrhage in horses, or by intranasal fungal infection or
neoplasia, systemic coagulopathy, vasculitis, thrombocytopenia (immune-mediated or a result of
rickettsial infection), hyperviscosity syndrome, hypertension, or nasal trauma. Hemoptysis (the
coughing up of blood) occurs after rupture of pulmonary aneurysms in the lungs of cattle with
chronic lung abscesses. Bleeding may also result from polyps, neoplasms, granulomas, trauma,
thrombocytopenia, and bracken fern or sweet clover toxicity.
LO#3- Identify basic circulatory pathological disorders
1.1. Causes and consequences of impaired blood supply to tissues/ organs

3.1.1. Introduction
Impaired blood supply is the disturbance of blood out of the right direction or impairment of the
blood content that reaches to the cell. The known impaired blood supply is ischemia and
infarction

3.1.2. Causes of impaired blood supply

A. Thrombosis: is a formation of clotted mass of blood within the cardiovascular system,
while blood clot is a clump of blood that has changed from a liquid to a gel-like or
semisolid state .Differences between thrombus and blood clot
Formation Composition Prognosis
Thrombus  Blood vessels  Platelets  Life threatening
 Platelets  Fibrin
 Blood clotting system
Blood clot  Blood clotting system  Only fibrin  Life saving

 Causes for thrombosis

 Trauma : lacerations, contusion, rupture, o/r injection
 Toxins : Streptococci, erysipelothrix (vegetations)
 Degenerations : Atherosclerosis (damage to intima)
 Viruses : Hog cholera virus
 Parasites : Strongylus vulgaris in anterior mesenteric artery in horses
 Tumours : Invading tumours
 Mechanism of thrombus formation
 Active
- Antithrombotic factors and prothrombotic factors are seen on surface of
endothelium
 Passive
 Endothelium is thrombo-resistant whereas sub-endothelial connective tissue is
highly thrombogenic.
- Sub-endothelial connective tissue consists of collagen, elastic, fibrinonectin,
laminin glycosoaminoglycans and thrombosporin.
- Damage to endothelium exposes the sub-endothelial connective tissue and
activates intrinsic blood clotting pathway and platelet adhesion.
 Antithrombotic factors (present on endothelial cells) - Inhibit thrombosis
 Anticoagulant properties
 Thrombo modulin - Protect against action of heparin and thrombin
which converts fibrinogen to fibrin
 Anti-platelet properties - Inhibit platelet aggregation
 Prostacyclin (PGI2)
 Nitric oxide (NO2)
 Fibrinolytic properties
 Tissue plasminogen activator (tPAs) - Promotes fibrinolytic
activity in blood and reacts against blood clots
 Thrombotic factors
 Tissue factor (Thromboplastin)
 Present on endothelium in small amounts
 Activate extrinsic clottingpathway
 Stimulated by
 Endotoxins
 Cytokines (IL – 1)
 Tumour necrosis factor (TNF)
 von Willebrand factor (vWF)
 Protein helps in platelet adherence thrombus
 Platelet Activating Factor (PAF)
 Helps in platelet aggregation thrombus
 Inhibitor of Plasminogen Activator
 Prevents fibrinolysis thrombus
Notes
  Normal homeostasis: There will be a balance between antithrombotic and prothrombotic
factors in normal endothelium.
B. Embolism
An embolus is any foreign body floating in blood. The process is called embolism.
 Location of embolism
 Artery / venous / capillaries / lymphatics
 In domestic animals emboli always occurs in arteries
 In human, venous embolism is common
 Thrombus in leg vein may form emboli to reach large blood vessel, right side heart and
pulmonary artery embolism
 Types / Causes of emboli
 Thrombotic emboli : Thrombo embolism – arteries (Thrombi detach to form emboli)
 Heart – vegetations
 Parasitic; atherosclerotic; bacteria
 Bacterial emboli : Septicaemia
 Parasitic emboli : Dirofilariaimmitis - Pulmonary artery – dog
 Schistosomes – Portal; mesenteric; Nasal blood vessels
 Trypanasomes – If tartar emetic is given rapidly, it kills large number of organism
and forms emboli on coronary vessels which is fatal.
 Filarial - Lymphatics emboli in brain
 Neoplastic emboli: Clumps of tumour cells in circulation producing metastatic tumours.
 Fibrin - In blood transfusion, when blood is improperly defibrinated / inadequate
anticoagulants
 Fat embolus - In fracture of long bones, fat in the marrow cavity gets dislodged and
forms emboli. These are lodged in lungs and leads to death.
 “Fat embolism syndrome“ (Acute respiratory symptoms, tachycardia neurological
symptoms)
 Air or gas emboli
C. Vasoconstriction: is the narrowing (constriction) of blood vessels by small muscles in their
walls.
 When blood vessels constrict, blood flow is slowed or blocked.Vasoconstriction
may be slight or severe. It may result from disease, drugs, or psychological
conditions.
D. Aneurysm: (dilation or outpouching of a blood vessel wall) are pathologic abnormalities
that can occur within the vasculature.

i. Consequence of impaired blood spplay.

Ischemia is decreased blood flow to or from an organ, while infarction is the cellular
response to lack of perfusion (blocked blood flow to or from organs).Ischemia can be
caused by obstruction of arterial blood flow – the most common cause, or by decreased
perfusion of tissues by oxygen-carrying blood as occurs in cardiac failure, hypotension, &
shock.
 Nature and characteristics of ischemia
Ischemia is a restriction in blood supply to tissues, causing a shortage
of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is
deficiency of arterial blood in any part of an organ. It is also known as local
anemia local anemia.
 Description
 Decreased blood supply that cannot meet the oxygen demands of an organ or tissue
 If not corrected, ischemia can lead to cell death due to cellular swelling (orcosis).
 Pathogenesis
 Decreased arterial perfusion (e.g., due to atherosclerosis, thromboembolism) in solid
organs with only a single (end-arterial) blood supply (e.g., kidney, heart) → pale infarct
 Decreased venous drainage (e.g., venous occlusion, Budd-Chiari syndrome, testicular
torsion, ovarian torsion) in tissues with more than one blood supply (e.g., intestine, lung,
liver, testes) or reperfusion (e.g., following angioplasty) → red infarct
 Shock with the following variants:
- Hypovolemic shock(e.g., hemorrhage) → ↓ intravascular volume → ↓ delivery of
oxygen to tissue → ischemia
 - Cardiogenic shock(e.g., cardiac tamponade) → ↓ left ventricular function → ↓
forward flow of blood → ↓ delivery of oxygen to tissue → ischemia
- Distributive shock (e.g., septic, neurogenic, and anaphylactic shock) → systemic
vasodilation → peripheral pooling of blood → ↓ delivery of oxygen to tissue →
ischemia.

 Pathophysiology of ischemia

Ischemia results in tissue damage in a process known as ischemic cascade. The damage is the
result of the:
 Build-up of metabolic waste products,
 Inability to maintain cell membranes,
 Mitochondrial damage, and
 Leakage of autolyzing proteolytic enzymes into the cell and surrounding tissues
 Cardiac arrhythmias (irregular heart beat; too fast or slow)
 Cellular self-destruction
 Damage white blood cells
 Etiology
 Occlusion: The thrombi may dislodge and may travel anywhere in the circulatory system,
where they may lead to pulmonary embolus, an acute arterial occlusion causing the
oxygen and blood supply distal to the embolus to decrease suddenly.
 Trauma: traumatic injury to an extremity may produce partial or total occlusion of a
vessel from compression, shearing, or laceration.
 External pressure on artery
 Narrowing / obliteration of lumen of artery
 Thrombi / emboli
 Notes
Ischemia: Death of cell by absences of blood supply or lack of oxygenated blood
oncosis: Death of cells with swelling.
Necrosis: Cell death by environmental stimuli with uncontrolled release of inflammatory
cellular contents.
Infarction: Cell death by occlusion of blood supply veins or arteries
  Infarction
An infract is an area of ischemic necrosis caused by occlusion of either the arterial supply or
venous drainage in a particular tissue. Nearly 99% of all infarcts result from thrombotic or
embolic events. Other mechanisms include (all of them are arterial in origin): Local vasospasm,
Expansion of atheroma due to hemorrhage in to athermanous plaque, External
compression of the vessels. E.g. trauma, Entrapment of vessels at hernial rings etc.
 The development & the size of an infarct are determined by the following
factors:
 The nature of the vascular supply
 The rate of development of occlusion
 Susceptibility of the tissue for hypoxia
 Oxygen content of the blood
 The severity and duration of ischemia
 The nature of vascular supply
The following organs have a dual blood supply.
 Lung → pulumonary artery → Bronchial artery
 Liver → hepatic artery → Portal vein
 Hand & forearm → Radial arteries → Ulnar arteries.
The effect of such a dual blood supply is that if there is obstruction of one of the arterial supplies,
the other one may offset the rapid occurrence of infarction in these organs unlike the renal &
splenic circulations which have end arterial supply. Infarction caused by venous thrombosis is
more likely to occur in organs with single venous outflow channels, such as testis &ovary.
 Rate of development occlusion
Slowly developing occlusions are less likely to cause infraction since they provide time for the
development of collaterals.
 Tissue susceptibility to hypoxia
The susceptibility of a tissue to hypoxia influences the likelihood of infarction. Neurons undergo
irreversible damage when deprived of their blood supply for only 3 to 4 minutes. Myocardial
cells die after 20-30 minutes of ischemia. Fibroblasts are more resistant, especially those in the
myocardium.
  Oxygen content of blood
Partial obstruction of the flow of blood in an anaemic or cyanotic patient may lead
to tissue infarction.
 The severity & duration of ischemia.
 Types of infarcts
Infarcts are classified depending on:
 The basis of their colour (reflecting the amount of hemorrhage) into:
a. Hemorrhagic (Red) infarcts
b. Anemic (White) infarcts
 The presence or absence of microbial infection into:
I. Septic infarcts
II. Bland infarcts
a. Red infarcts occur in:
 Venous occlusions as in ovarian torsion
 Loose tissues such as the lung which allow blood to collect in infarct zone.
 Tissues with dual circulations (e.g. the lung), permitting flow of blood from
unobstructed vessel in to necrotic zone.
 In tissues that were previously congested because of sluggish outflow of blood.
 When blood flow is reestablished to a site of previous arterial occlusion &
necrosis.
b. White infarcts occur in:
 Arterial occlusion in organs with a single arterial blood supply.
 Solid organs such as the heart, spleen, & kidney, where the solidity of the tissue limits
the amount of hemorrage that can percolate or seep in to the area of ischemic necrosis
from the nearby capillaries.
 Morphology of infarcts
Gross: All infarcts are wedge-shaped with the occluded vessel at the apex and the periphery of
the organ forming the base of the wedge. The infarction will induce inflammation in the tissue
surrounding the area of infarction. Following inflammation, some of the infarcts may show
recovery, however, most are ultimately replaced with scars except in the brain.
Microscopy: The dominant histologic feature of infarction is ischemic coagulative necrosis. The
brain is an exception to this generalization, where liquefactive necrosis is common.
 Clinical examples of infarction:
 Myocardial infarction
 Usually results from occlusive thrombosis supervening on ulcerating
atheroma of a major coronary artery.
 Is a white infarct.
 Can cause sudden death, cardiac failure, etc.

 Cerebral infarcts
 May appear as pale or hemorrhagic
 A fatal increase in intracranial pressure may occur due to swelling of large cerebral
infarction, as recent infarcts are raised above the surface since hypoxic cells lack the
ability to maintain ionic gradients & they absorb water & swell.
 Is one type of cerebrovascular accidents (CVA) or stroke which has various clinical
manifestations.
 Lung infarcts
 Are typically dark red & conical (wedge-shaped).
 Can cause chest pain, hemoptysis, etc.
 Splenic infarcts
 Conical & sub capsular
 Initially dark red later turned to be pale.
3.1.3. Pathological lesions in circulatory disturbances

I. Jaundice/Icterus

Icterus is increased amount of bile pigments in blood circulation and is often called as hyper-
bilirubinemia or jaundice. It is of three types.
 Hemolytic
Hemolytic jaundice occurs as a result of excessive hemolysis in circulating blood. It is also
known as prehepatic jaundice.
 Etiology
 Piroplasmosis (Babesiabigemina)
 Anaplasmosis (Anaplasma marginale)
 Leptospirosis(Leptospira ictehaemmorrhagae)
 Equine infectious anemia virus
 Anthrax (Bacillus anthracis)
 Clostriduumhemolyticum
 haemolytic streptococci

 Toxic
Toxic jaundice occurs as a result of damage in liver leading to increased amount of unconjugated
and conjugated bilirubin in blood. It is also known as hepatic jaundice.
 Etiology
 Toxinj Poisons
 Copper poisoning
 Leptospirosis

 Obstructive Jaundice:
Occurs as a result of obstruction in bile duct causing hindrance in normal flow of bile. It is
also known as post hepatic jaundice.
 Etiology
 Blocking of bile canaliculi by swollen hepatocytes
 Obstruction in bile duct (Liver flukes, tapeworms and ascaris)
 Biliary cirrhosis, Cholangitis and Cholelithiasis
  Pressure on bile duct due to abscess, neoplasm.
 Inflammation and swelling at duct opening in duodenum

II. Hyperaemia
Hyperaemia is increased volume of blood in affected tissue or part.
 Hyperaemia (Active hyperaemia)
 Occurs in arterioles or arteries
 Increased blood flow in capillaries
 Congestion (Passive hyperaemia)
 Occurs due to impaired venous drainage
 Stasis of blood in veins
 Classification of Hyperaemia
 Active Hyperaemia
 Increased blood in arterial side
 Usually due to inflammation
 All active hyperaemia are acute
 Chronic active hyperaemia does not occur
 Occurs when there is a demand for oxygen and nutrients - increase metabolismIt
is beneficial.
 Acute General Active Hyperaemia
 Increased blood throughout the body
 Causes
- Various systemic diseases. E.g. Pasteurellosis, erysipelas Rapidly beating heart →
increased blood supply
- Renal diseases - due to retention of fluids
 Macroscopically
- Bright red color organs
 Microscopically
- Arteries and capillaries dilated with blood

 Result
- Disappears if cause is removed

 Acute Local Active Hyperaemia

  Increased amount of blood in arterial system within a local area (leg, Stomach, lung)
 Most common type of hyperaemia
Causes
 Physiological
 Occurs in stomach and intestine following a meal
 Lactating mammary gland
 Muscles during exercise
 Genital tract during oestrus
 Blushing
 Acute inflammation
Macroscopically
 Enlarged, swollen, heary
 ↑ warmth in Skin
 Microscopically
 In live animals, arteries, arterioles and capillaries are distended with blood
 Difficult to detect in dead animals.
III. Congestion :
It is increased blood in the venous end due to improper drainage. .It can be: general if
interference is central (i.e.) lungs, heart or Local, if vein of an organ or body it can be acute or
chronic venous congestion is more common
 Types of congestion
A. Acute
This is occurred when Increase in the amount of blood on the venous side of circulatory
system Due to sudden obstruction to the flow of blood in heart and lungs.
 Causes
 Heart failure
 Degeneration and necrosis of myocardium
 Myocardial infarction
 Pneumonia
 Pulmonary thrombosis or embolism
 Hydropericardium, Haemopericadium, etc.
  Hydrothorax, Haemothorax, etc.
 Macroscopically
- Organs are blue in color (Unoxygenated blood)
- Veins distended with blood
- Organs enlarged, heavy
- Upon incision, blood oozes out
 Result
 Causes are mild → Recovery
 Causes are severe → Death
B. Chronic
 Increased blood on venous end persisting for long period of time causes Permanent changes
(fibrosis, atrophy). Due to central lesions in heart and lungs.
 Heart lesions
 Stenosis of valvular openings
 Valvular insufficiency
 Failure of cusps of valves to close property
 Inflammatory tissue
 Thrombus
 Myocardial failure: Degeneration and necrosis of muscles
 Anomalies of heart
 Persistent foramen orale
 Interventricular septal defects
 Constrictive lesons in pericardium
 Traumatic pericarditis in cattle
 Lesions of lungs
 Obliteration of capillary bed in lungs
 Prevents free flow of blood through the lungs
 Retards flow through right side of heart
 Blood back flows into Liver
 It Causes(results):
 Chronic alveolar pulmonary emphysema in horses (BROKEN WIND)
  Pneumonia
 Hydrothorax, haemothorax
 Compression of major pulmonary vessels
-Tumours
-Cysts
-Abscesses.
C. Acute Local
Increase in blood in the veins of a portion (foot, tail, kidney etc) Due to sudden obstruction to
blood flow
 It Causes (results)
 Malposition of viscera
 Volvulus, intussusception, torsion
 External pressure
 Ligatures, tourniquets, bandages
 Pathogenesis
 Hydrostatic: Accumulation of blood in ventral portions of the body due to gravity..
 Causes(etiology)
 Occurs in heart diseases
 Recumbency
 Inactive animals
 Large animals
 Heart failure - Agonal congestion
  Appearances
 Veins in ventral portion or organs distended with blood
 Lungs - increase capillary bed
 Intestine & kidneys – necrosis and gangrene
 Causes pneumonia and gangrene of intestine
 Significance; Indicates.
 the side of animals which was ventral at the time of death
 Heart was not able to pump properly
 Location of body in medico–legal cases
 Grossly and microscopically
Veins are engorged with blood Necrosis of endothelial cells Haemorrhage
D. Chronic Local; this is due to bIncrease in amount of blood for a long time in veins,
results in Permanent tissue changes (atrophy, fibrosis).
 Causes
 External pressure
 Tumors, abscesses
 Obstruction from within
 Thrombus (blood clot)
 Gross and microscopic appearance
 Enlarged initially later undergoes atrophy
 Veins - bluish blood
 Oedema due to increase permeability of capillaries
 Fibrosis

3.2. Aetiology for development of congestion and jaundice/icterus

3.2.1. Aetiology for development of congestion

Congestion is a Passive hyperemia (Venous congestion).it can be an acute or chronic case.
It is increased volume of blood in the venous side of the vascular system due to interference
venous return from tissue.
  Classification of congestion
Active hyperemia may be classified according to duration and affected area into:
I. General venous congestion.
II. Local venous congestion.

i. General venous congestion

Causes
As mentioned before venous congestion occurs due to interference of blood flow. Moreover
acute general venous congestion are resulting from any cause interfere with blood flow through
heart and lungs. Degeneration and necrosis of myocardium, in animal put to sever exercise after
a prolonged rest or in some infectious diseases, beside interference with flow of blood in lungs,
in case of pneumonia where exudates compress the capillaries, are the common causes.

ii. Hypostatic congestion (acute local passive congestion)

It is the gravitation of blood in the lowermost portion of the body. It is usually caused by
cardiac defect, which fail to maintain sufficient blood pressure to overcome the force of gravity.

Pathogenesis
The defect in heart, or lungs lead to accumulation of blood in venous side with increase of CO2
concentration, which affect on the endothelial lining of capillaries and venules leading to
increase its permeability and permits plasma to escape to tissue and serous cavities. Moreover,
increase CO2 concentration stimulates fibroblast proliferation. Pressure atrophy results from
persist of large amount of blood in venous side.

3.2.2. Aetiology for development jaundice/icterus

Jaundice is a condition in which a yellowish tinge appears on the skin, mucous membranes, and
the whites of the eye. Body fluids may also change color.
Jaundice frequently indicates a problem with the liver or bile ducts. When the liver is not
working properly, it can cause a waste material called bilirubin to build up in the blood.
With moderate bilirubin levels, the skin, eyes, and mucous membranes can turn yellow. As it
progresses, the color can also change from yellow to green. The green color occurs due to
biliverdin, the green pigment present in bile.
Jaundice can develop in people of all ages and is normally the result of an underlying condition.
Newborns and older adults have the highest likelihood of developing jaundice. Bilirubin levels
increase as the red blood cells naturally break down. Typically, the liver filters this waste
material out of the bloodstream and turns it into a new form called conjugated bilirubin. The new
form then exits the body in a person’s stool. If there is too much bilirubin for the liver to process,
it can build up in the body. This is known as hyper bilirubinemia, and it causes the yellow color
in the skin and eyes.

Jaundice typically occurs due to an underlying disorder that either causes the production of too
much bilirubin or prevents the liver from eliminating it.
Some possible underlying conditions and causes of jaundice include:
 side effects of certain medications
 gallstone disease
 excessive alcohol consumption
 gallbladder or pancreatic cancer
 cirrhosis, which is a disease that causes scar tissue to replace healthy tissue in the liver
 hepatitis or other liver infections
 hemolytic anemia

3.3. Types and causes of shock

Shock
Definition: Shock is a state in which there is failure of the circulatory system to maintain
adequate cellular perfusion resulting in widespread reduction in delivery of oxygen & other
nutrients to tissues. In shock, the mean arterial pressure is less than 60 mmHg or the systolic
blood pressure is less than 90 mmHg.Adequate organ perfusion depends on arterial blood
pressure (BP) which, in turn, depends on:
 Cardiac output.
 Peripheral vascular resistance.
Cardiac output = stroke volume X heart rate
In turn, stroke volume depends on:
a. Preload i.e. blood volume,
b. Afterload i.e. arterial resistance, &
c. Myocardial contractility.
Therefore, shock (i.e. widespread decreased perfusion of tissues) occurs when the preload (i.e.
the blood volume) is decreased, or when the afterload (the peripheral vascular resistance) is
decreased, or when the myocardium fails to contract. These basic mechanisms of shock are used
to classify it. Next, we will look at the classification of shock.
3.3.1. Types of shock: Shock can be divided into:
I. Hypovolemic shock
II. Cardiogenic shock
III. Distributive shock
I. Hypovolemic shock
Definition: This is shock caused by reduced blood volume. Reduction in circulating blood
volume results in the reduction of the preload which leads to inadequate left ventricular filling,
reflected as decreased left & right ventricular end diastolic volume and pressure. The reduced
preload culminates in decreased cardiac output which leads to widespread tissue perfusion
(shock).
 Causes of hypovolumic shock include:
 Haemorrhage  Burns
 Diarrhoea and vomiting  Trauma and etc.
The effect of haemorrhage depends on the rate and amount of blood loss. Hypovolumic shock is
the most common type of shock in clinical medicine .A normal healthy adult can lose 550ml
(10%of blood volume) without significant symptoms.
II. Cardiogenic shock
Definition: This is shock that results from severe depression of cardiac performance. It primarily
results from pump failure (myocardial failure). Causes of cardiogenic shock can be divided into:
A. Myopathic
B. Mechanical
A. Myopathic causes of cardiogenic shock include:
 Acute myocardial infraction. Usually shock occurs in this conditioin if ≥ 40% of the left
ventricular mass & more on the right ventricle is involved by infarction.
 Mycocarditis
 Dilated cardiomyopathy/hypertrophic cardiomyopathy
 Myocardial depression in septic shock and etc.
B. Mechanical
 Intracardiac
 Left ventricle outflow obstruction E.g.Aortic stenosis, hypertrophic cardiomyopathy
 Reduction in forward cardiac output E.g. Aortic or mitral regurgitation
 Arrhythmia
 Extracardiac

This can be called obstructive shock. The extracardiac causes of cardiogenic shock can be caused
by:
 Pericardial tamponade (gross fluid accumulation in the pericardial space) results in a
decreased ventricular diastolic filling → ↓CO
 Tension pneumothorax (gas accumulation in pleural space). This decreases the venous
return by creating a positive pressure.
 Acute massive pulumonary embolism occupying 50-60% of pulumonary vascular bed.
 Severe pulmonary hypertension (10pulmonary hypertension).
III.Distributive shock
Definition: Distributive shock refers to a group of shock subtypes caused by profound peripheral
vasodilatation despite normal or high cardiac output.
Causes of distributive shock:
 Septic shock – the commonest among the group& clinically very important.
 Neurogenic shock
 Usually occurs in the setting of anaesthetic procedure [cephalo-caudal migration of
anaesthetic agent] or spinal cord injury owing to loss of vascular tone &peripheral pooling
of blood.
 Anaphylactic shock
 Initiated by generalized IgE – mediated hypersensitivity response, associated with
systemic vasodilatation & increased vascular permeability.
 Endocrine shock
 This is a type of shock that typically occurs in adrenal insufficiency.
Notes
 Bactermia:is the presence of viable bacteria in the blood as evidenced by blood culture.
 Septicemia:is systemic infection due the presence of microbes and their toxin the blood.
 Sepsis:is a systemic response to severe infection mediated via macrophage-derived
cytokines that target end organ receptors in response to infection.

LO#4- Recognize Growth disorder

4.1. Congenital defects of body systems

Introduction to congenital defects

Congenital anomalies can be defined as structural or functional anomalies that occur during
intrauterine life. Also called birth defects, congenital disorders, or congenital malformations,
these conditions develop prenatally and may be identified before or at birth, or later in life.
 Figure 4.1 :Congenital defeacts occurred at animals level

4.1.1. Disturbances in Development (Anomalies & Monster)

 Anomaly is developmental defect affecting an organ or part of the body.
 Anomaly is the disturbance of development that involves an organ or a portion of
an organ.
 Monster is an animal in which extensive abnormal developments are present.
 A Congenital disease is one in which the patient is born with the disease whereas an
inherited disease is one which is due to factors in the genetic materials received
from the parents.

4.1.2. Classification of Anomalies

A. Arrest of Development
 Agenesia is an incomplete and imperfect development of an organ or part and aplasia is
absence of an organ or part. There some exaamples of agenesis and aplasia lists:
 Acrania is absence of most or all of the bones of the cranium.
 Amelia is absence of one or more limbs.
 Agnathia is absence of lower jaw.
 Anencephalia is absence of the brain
 Hypocephalia is incomplete development of the brain.
 Anophathalmia is absence of one or both eyes.
  Hemicrania is absence of half of the head.
 Atresia is absence of normal opening e.g. Atresia ani is absence of anus opening and
Atresia coli is absence of rectum.
 Exencephalia is defective skull with brain exposed or extruded. If the protruding brain
contains a ventricle which is filled with excessive amount of fluid, the malformation is
a hydrencephalocele.
 Arhinencephalia is absence or rudimentary development of the olfactory lobe with
corresponding lack of development of the external olfactory organs.
 Agnathia is absence of the lower jaw.
 Anophthalmiais absence of one or both eyes.
 Abrachia is absence of the forelimbs.
 Abrachiocephalia is absence of forelimbs and head.
 Adactylia is absence of digits.

Figure 4.2: Anomalies of Atresia, Anophthalmia and Anencephalia

 Fissures on the median line of the head, thorax, and abdomen.

 Craniooschisis (skull)
 Cheiloschisis (lip), often referred to as harelip.
 Palatoschisis (oral) cavity, often called cleft palate. Harelip and cleft palate result from
faulty development of the maxillary process derived from the first visceral arch.
 Rachischisis (spinal column).
  Schistorrachis or spina bifida (spinal column)
 Schistothorax (thoraz or sternum).
 Schistosomus (abdomen).
 Schistocormus (thorax, neck or abdominal wall). Results from arrested development of
the amnion.

Figure 4.3 : Organs monasteries indications of some animals

 Fusion of paired organs

 Cyclopia (eyes)
 Ren arcuatus (kidneys), often referred to as horseshoe kidney.
B. Excess of Development
 Congenital hypertrophy
 Hemi hypertrophy (partial)
 Increase in the number of a part.

 Polyotia (ears)  Polydactylia(digits)

 Polyodontia(teeth)  Polymastia (mammary gland)
 Polymelia (limbs)  Polythelia(teat

4.1.3. Displacements During Development

I. Displacements of organs
 Dextrocardia is transposition of the heart to the right side.
 Ectopiacordiscervicalis is displacement of the heart into the neck.
 II. Displacements of tissues
 Teratoma is inclusion of multiple displaced and also neoplastic tissues within an
individual.
 Dermoid is inclusion within an individual of a mass containing skin, hair, feathers, or
teeth depending on the species and often arranged as an epidermal cyst (Dermoid
cyst).
 Odontoid cyst is inclusion within an individual of a mass of dental enamel and
cement.
 Dentigerous cyst is inclusion within an individual of one or more imperfectly formed
teeth.
 Fusion of Sexual Characters
 Hermaphrodite is an individual having both testicular and ovarian tissue.
Pseudohermaphrodite is an animal having unisexual development of the sex glands
(either testicular or ovarian tissue), but having also either a unisexual or bisexual
development of the other parts of the genitalia.
 Freemartin is a female calf having arrested development of the sex organs and being
the twin of perfect male.

iii. Monsters
A monster or monstrosity is a disturbance of development that involves several organs and
causes great distortion of the individual. For the most part monsters possess a duplication of all
or most of the organs and other parts of the body. They develop from a single ovum. They are
therefore the product of incomplete twinning.

Classification of the Monsters

a. Twins Entirely Separate
Although separate, these twins are in a single chorion. One twin as a rule is well
developed; the other is malformed (acardius). In the malformed foetus there is arrested
development of the heart, lungs, and trunk. Such monsters may lack a head (acephalus),
limbs and other recognizable features (amorphous), or the trunk (acormus).
b. Twins United; these twins are more or less completely united and are of symmetrical
development.
 a. Twins United
 Anterior Twinning: The anterior part of the individual is double, the posterior single.
 Pygopagus – united in the pelvic region with the bodies side by side.
 Ischiopagus – united in the pelvic region with the bodies at an obtuse (not pointed) angle.
 Dicephalus – two separate heads; doubling may also affect the neck, thorax and trunk.
 Diproosopus – doubling in the cephalic region without complete separation of heads;
only the face doubled.

 Posterior Twinning:The posterior part is double, the anterior single.

 Craniopagus – brains usually separated; bodies as a rule at an acute angle.
 Cephalothoracopagus – union of head and thorax.
 Dipygus – doubling of posterior extremities and posterior part of body.

 Two animal
created as
one and 6
legs

Twins united

Figure 4.4: twins united anomalies

b. Twinning Almost Complete

Duplication of the whole trunk or the anterioror posterior extremities with parallel, ventral
arrangement of the foetuses. The pair is joined in the region of the thorax, and also often in the
abdominal region.
 Thoracopagus – united only by the thorax.
  Prosopothoracopagus – besides the union the thorax the abdomen, the head and neck are
united.
 Rachipagus – thorax and lumbar portion of the spinal column united.

4.2. Adaptive changes in animal cells

4.2.1. Cellular changes and adaptive responses

Cellular adaptation is the ability of cells to respond to various types of stimuli and adverse
environmental changes. Tissues adapt differently depending on the replicative characteristics of
the cells that make up the tissue. For example, labile tissue such as the skin can rapidly replicate,
and therefore can also regenerate after injury, whereas permanent tissue such as neural and
cardiac tissue cannot regenerate after injury. If cells are not able to adapt to the adverse
environmental changes, cell death occurs physiologically in the form of apoptosis, or
pathologically, in the form of necrosis. This article provides an overview of the main cellular
adaptive mechanisms and their different consequences in the human body. Cellular adaptations
include:
 Hypertrophy (enlargement of individual cells),
 Hyperplasia (increase in cell number),
 Atrophy (reduction in size and cell number),
 Metaplasia (transformation from one type of epithelium to another), and
 Dysplasia (disordered growth of cells).
Tissues adapt differently depending on the replicative characteristics of the cells that make up the
tissue. For example, labile tissue such as the skin can rapidly replicate, and therefore can also
regenerate after injury, whereas permanent tissue such as neural and cardiac tissue cannot
regenerate after injury. If cells are not able to adapt to the adverse environmental changes, cell
death occurs physiologically in the form of apoptosis, or pathologically, in the form of necrosis.

4.2.2. Types of cellular adaptation

I. Hypertrophy
Hypertrophy is increase in the size of cells. Increased workload leads to increased protein
synthesis & increased size & number of intracellular organelles which, in turn, leads to increased
 cell size. The increased cell size leads to increased size of the organ.E.g.: the enlargement of the
left ventricle in hypertensive heart disease & the increase in skeletal muscle during sternous
exercise.

II. Hyperplasia
Hyperplasia is an increase in the number of cells. It can lead to an increase in the size of the
organ. It is usually caused by hormonal stimulation. It can be physiological as in enlargement of
the breast during pregnancy or it can pathological as in endometrial hyperplasia.
III. Atrophy
Atrophy is a decrease in the size of a cell. This can lead to decreased size of the organ. The
atrophic cell shows autophagic vacuoles which contain cellular debris from degraded organelles.
Atrophy can be caused by:
 Disuse
 Undernutrition
 Decreased endocrine stimulation
 denervation
 Old age

IV. Metaplasia
Metaplasia is the replacement of one differentiated tissue by another differentiated tissue. There
are different types of metaplasia. Examples include:

a. Squamous metaplasia: this is replacement of another type of epithelium by squamous

epithelium. For example, the columnar epithelium of the bronchus can be replaced by
squamous epithelium in cigarette smokers
b. Osseous metaplasia: this replacement of a connective tissue by bone, for example at sites
of injury.
V. Dysplasia
A term used to describe the presence of abnormal cells within a tissue or organ. Dysplasia is not
cancer, but it may sometimes become cancer. Dysplasia can be mild, moderate, or severe,
depending on how abnormal the cells look under a microscope and how much of the tissue or
organ is affected.

Figure 4.5: Organs and bovine heart hypertrophy

Figure 4.6: Development of metaplasia in oral cavity of both animals and plant

4.2. Characteristics and common types of neoplasia

 4.3.1. Characteristics of neoplasia
Neoplasia
Neoplasia is the abnormal growth of a tissue into a mass that is not responsive to normal control
mechanisms and may be benign or malignant. Growth of this mass is not affected when the
inciting stimulus is removed.
Overview: The terms tumor, nodule, and mass are nonspecific terms that refer to an abnormal
proliferation of cells. The term neoplasm means new growth and does not imply benign or
malignant (i.e., there are benign neoplasms, and there are malignant neoplasms).

A. Nomenclature for general categories of neoplasms

I. Adenoma: Benign neoplasm derived from glandular cells.

Adenoma is a type of non-cancerous tumor or benign that may affect various organs. It is
derived from the word “adeno” meaning 'pertaining to a gland'. Every cell in the body has a
tightly regulated system that dictates when it needs to grow, mature and eventually die off.

II. Carcinoma: Malignant neoplasm derived from epithelial cells.

 Carcinoma refers to a malignant neoplasm of epithelial origin or cancer of the internal or
external lining of the body. Carcinomas, malignancies of epithelial tissue, account for 80 to
90 percent of all cancer cases.
 Epithelial tissue is found throughout the body. It is present in the skin, as well as the
covering and lining of organs and internal passageways, such as the gastrointestinal tract.
 Carcinomas are divided into two major subtypes: adenocarcinoma, which develops in an
organ or gland, and squamous cell carcinoma, which originates in the squamous
epithelium.
 Adenocarcinomas generally occur in mucus membranes and are first seen as a thickened
plaque-like white mucosa. They often spread easily through the soft tissue where they
occur. Squamous cell carcinomas occur in many areas of the body.
  Most carcinomas affect organs or glands capable of secretion, such as the breasts, which
produce milk, or the lungs, which secrete mucus, or colon or prostate or bladder.

III. Sarcoma: Malignant neoplasm derived from mesenchymal cells (e.g., fat, muscle).
Sarcoma refers to cancer that originates in supportive and connective tissues such as bones,
tendons, cartilage, muscle, and fat. Generally occurring in young adults, the most common
sarcoma often develops as a painful mass on the bone. Sarcoma tumors usually resemble the
tissue in which they grow. Examples of sarcomas are:
 Osteosarcoma or osteogenic sarcoma (bone)
 Chondrosarcoma (cartilage)
 Leiomyosarcoma (smooth muscle)
 Rhabdomyosarcoma (skeletal muscle)
 Mesothelial sarcoma or mesothelioma (membranous lining of body cavities)
 Fibrosarcoma (fibrous tissue)
 Angiosarcoma or hemangioendothelioma (blood vessels)
 Liposarcoma (adipose tissue)
 Glioma or astrocytoma (neurogenic connective tissue found in the brain)
 Myxosarcoma (primitive embryonic connective tissue)
 Mesenchymous or mixed mesodermal tumor (mixed connective tissue types)

IV. Lymphoma: Malignant neoplasm derived from lymphocytes.

Lymphomas develop in the glands or nodes of the lymphatic system, a network of vessels, nodes,
and organs (specifically the spleen, tonsils, and thymus) that purify bodily fluids and produce
infection-fighting white blood cells, or lymphocytes. Unlike the leukemia’s which are sometimes
called "liquid cancers," lymphomas are "solid cancers." Lymphomas may also occur in specific
organs such as the stomach, breast or brain. These lymphomas are referred to as extra
nodal lymphomas. The lymphomas are sub-classified into two categories: Hodgkin
lymphoma and Non-Hodgkin lymphoma. The presence of Reed-Sternberg cells in
Hodgkin lymphoma diagnostically distinguishes Hodgkin lymphoma from Non-Hodgkin
lymphoma.

V. Melanoma: Malignant neoplasm derived from melanocytes.

 Myeloma is cancer that originates in the plasma cells of bone marrow. The plasma cells produce
some of the proteins found in blood.

 Leukemia
Leukemias ("liquid cancers" or "blood cancers") are cancers of the bone marrow (the site of
blood cell production). The word leukemia means "white blood" in Greek. The disease is often
associated with the overproduction of immature white blood cells. These immature white blood
cells do not perform as well as they should, therefore the patient is often prone to infection.
Leukemia also affects red blood cells and can cause poor blood clotting and fatigue due to
anemia. Examples of leukemia include:

 Myelogenous or granulocytic leukemia (malignancy of the myeloid and granulocytic white

blood cell series)
 Lymphatic, lymphocytic, or lymphoblastic leukemia (malignancy of the lymphoid and
lymphocytic blood cell series)
 Polycythemia vera or erythremia (malignancy of various blood cell products, but with red
cells predominating).

VI. Germ cell tumor: Malignant neoplasm derived from germ cells. The type components may
be within one category or from different categories. Some examples are:
 adenosquamous carcinoma
 mixed mesodermal tumor
 carcinosarcoma
 teratocarcinoma

B. Nomenclature for benign neoplasms

In general, the name of a benign neoplasm often ends with - oma.

 Examples: Adenoma (benign neoplasm of glandular epithelium), fibroadenoma (benign

neoplasm of the breast), and leiomyoma (benign neoplasm of smooth muscle).
 Some exceptions: Hepatoma (malignant neoplasm of liver), melanoma (malignant
neoplasm of melanocytes), mesothelioma (malignant neoplasm of mesothelial cells), and
 seminoma (malignant germ cell neoplasm of testis).

C. Nomenclature for malignant neoplasms

In general, the name of a malignant neoplasm often ends with –carcinoma or –sarcoma.
 Examples: Adenocarcinoma (malignant neoplasm of glandular tissue),
rhabdomyosarcoma (malignant neoplasm of skeletal muscle), and leiomyosarcoma
(malignant neoplasm of smooth muscle).

4.3.2. Common types of neoplasia

Definition and Nomenclature
Recently, neoplasiameans new growth and technically,defined as abnormal mass of tissues the
growth of which exceeds and persists in the same excessive manner after cessation of the
stimulus, evoking the transformation.
Nomenclature: Neoplasms are named based upon two factors:
 On the histologic types →mesenchymal and epithelial
 On behavioral patterns : benign and malignant neoplasms

Figure 4.7:Neoplasia of dog eye and eyelid

Neoplasms are classified so that one can:

 Deduce a prognosis
 Investigate the cause
 Perhaps with a view to prevention
 Assess the results of treatment.
  It must be remembered that there are several types of proliferative change, and neoplasia
must be distinguised from these.
 In addition to neoplasia, hyperplasia and dysplasia are also proliferative changes.
 Inflammatory, repair and granuloma lesions may also masquerade as neoplasms.
 However, destructive or necrotic tumours may have inflammation present.
 Unlike inflammation, hyperplasia or dysplasia, neoplastic cells show uncontrolled
proliferation in the absence of a triggering stimulus.

4.3.3. Types of Classification of neoplasim

Tumours are classified by:

a) Histogenesis: by identification of the cells/ tissue of origin.
b) Anatomical origin: by site of anatomical growth.
c) State of differentiation: by relative development or maturity of the cell type involved.
d) Behaviour: by host-tumour growth patterns.e.g. benign or malignant.

 Behaviour
 The terms ‘benign’ and ‘malignant’ represent two ends of a spectrum of behaviour patterns
in tumours.
 Certain features exhibited by the neoplastic cells allowtumours to be labelled as benign or
malignant.
a. Characteristics of Benign and Malignant Neoplasms
Benign neoplasia: Thus, the suffix -oma denotes a benign neoplasm. Benign mesenchymal
neoplasms originating from muscle, bone, fat, blood vessel nerve, fibrous tissue and cartilages
are named as Rhabdomyoma, osteoma, lipoma, hemangioma, neuroma, fibroma and chondroma
respectively. Benign epithelial neoplasms are classified on the basis of cell of origin for example
adenoma is the term for benign epithelial neoplasm that form glandular pattern or on basis of
microscopic or macroscopic patterns for example visible finger like or warty projection from
epithelial surface are referred to as papillomas.
Malignant neoplasm nomenclature essentially follows the same scheme used for benign
neoplasm with certain additions. Malignant neoplasms arising from mesenchymal tissues are
called sarcomas (Greed sar =fleshy). Thus, it is a fleshy tumour. These neoplasms are named as
fibrosarcoma, liposarcoma, osteosarcoma, hemangiosarcoma etc. Malignant neoplasms of
epithelial cell origin derived from any of the three germ layers are called carcinomas.

Eg. Ectodermal origin: skin (epidermis squamous cell carcinoma, basal cell carcinoma)
Mesodermal origin: renal tubules (renal cell carcinoma).Endodermal origin: linings of the
gastrointestinal tract (colonic carcinoma). The difference in characteristics of these neoplasms
can be conveniently discussed under the following:-

i. Differentiation & anaplasia

ii. Rate of growth
iii. Local invasion
iv. Metastasis
 i. Differentiation & anaplasia
Differentiation refers to the extent to which parenchymal cells resemble comparable normal cells both morphologically and
functionally.Thus, well-differentiated tumourscells resemble mature normal cells of tissue of origin. In general, benign neoplasms are
well differentiated. Malignant neoplasms in contrast, range from well differentiated, moderately differentiated to poorly differentiate
types. Malignant neoplasm composed of undifferentiated cells are said to be anaplastic, literally anaplasia means to form backward.
 Morphology of anaplastic cell includes large Pleomorphic; hyperchromatic nucleus with high nuclear cytoplasmic ratio
1:1(normally 1:4 to 1:6). The cell usually reveals large nucleoli with high and often abnormal mitoses. Tumour giant cells and
frequent loss of polarity of epithelial arrangements are encountered.
 On functional differentiation, the well differentiated the neoplasm, the more completely it retains the functional capabilities found
in its normal counterparts thus, endocrine tumours produce hormone (ex. Thyroid, adrenal) so also, well differentiated squamous
cell carcinoma and well differentiated hepatocellular carcinomas produce keratine and bile respectively.
 However, highly anaplastic or undifferentiated cells of what cell tissue of origin come to resemble each other functionally and
morphologically more than the normal cells which they have arisen this is called chemical convergence.

ii. Rate of growth

 Most benign tumours grow slowly whereas; most malignant tumours grow rapidly sometimes, at erratic pace.
 Some benign tumours for example uterine leiomyoma increase in size during pregnancy due to probably steroidal effects
(estrogen) and regress in menopause.
 In general, the growth rate of neoplasms correlate with their level of differentiation and thus, most malignant neoplasms grow
more rapidly than do benign neoplasms.
  On occasions, cancers have been observed to decrease in size and even spontaneously disappear. E.g. renal cell carcinoma,
malignant melanoma, choriocarcinoma.

iii. Local invasion

 Nearly all benign neoplasms grow as cohesive expansile masses that remains localized to their site of origin and do not have the
capacity to invade or metastasize to distant sites, as do malignant neoplasms.
 Rims of fibrous capsules encapsulate most benign neoplasms. However, hemangiomas and neuro fibromas are exceptions. Thus,
such encapsulations tend to contain the 193 benign neoplasms as a discrete, rapidly palpable and easily movable mass that can
easily surgically enucleated.
 The growth of malignant neoplasms is accompanied by progressive infiltration, invasion and destruction of the surrounding tissue.
Generally, they are poorly demarcated from the surrounding normal tissue (and a well-defined cleavage plane is lacking).
 Next to the development of metastasis, invasiveness is the most reliable feature that differentiates malignant from benign
neoplasms.
 Even though, malignant neoplasms can invade all tissues in the body, connective tissues are the favoured invasive path for most
malignant neoplasms, due to the elaboration of some enzymes such as type IV collagnases& plasmin, which is specific to collagen
of basement membrane. Several matrix-degrading enzymes including glycosidase may be associated with tumour invasion.

iv. Metastasis
 It is defined as a transfer of malignant cells from one site to another not directly connected with it (as it is described in the above
steps).
 Metastasis is the most reliable sign of malignancy. The invasiveness of cancers permits them to penetrate in to the blood vessel,
lymphatic and body cavities providing the opportunity for spread.
  Most malignant neoplasm metastasies except few such as gliomas in the central nervous system, basal cell carcinoma (Rodent
ulcer) in the skin and dermato fibrosarcoma in soft tissues.
 Organs least favoured for metastatic spread include striated muscles and spleen.
 Since the pattern of metastasis is unpredictable, no judgment can be made about the possibility of metastasis from pathologic
examination of the primary tumour.

b. Pathways of spread:
Dissemination of malignant neoplasm may occur through one of the following pathways.
i. Seeding of body cavities and surfaces (transcoelomic spread)
ii. Lymphatic spread: The most common pathway for the initial dissemination of carcinomas
iii. Hematogenous spread