VPT 302: GRENERAL PATHOLOGY

Introduction to General Pathology

BY
Dr. S. O. Omotainse
 VPT 302: GENERAL PATHOLOGY

Pathology is the study of anatomical,

physiological and biochemical changes in the
host when exposed to disease agents or there is
deprivation of essential factors.
 VPT 302
CLASSIFICATION OF PATHOLOGY
•A. SUBSPECIALITIES
*General Pathology
*Systemic Pathology e.g. Respiratory,
GIT, etc
*Organs
*Clinical Pathology/Chemical Pathology
*Surgical Pathology e.g. Tumour
 VPT 302
A. RESEARCH
•Molecular pathology
•Ultra structural pathology
•Immunopathology
•Biochemical pathology
•Physiological pathology
*Exfoliative Cytology of cells obtained
from fluids, tracts, tissues e.g. of
female in pregnancy diagnosis, cancer.
 VPT 302

CELL INJURY AND DEATH

A. Cellular Adaptation
• i. Atrophy
• ii. Hypertrophy
• iii. Hyperplasia
• iv. Metaplasia
B. Cell Injury
C. Necrosis
D. Apoptosis
• Cellular Adaptation- adjusting their structures and
functions in response to physiological and
pathological conditions:
i. Atrophy- shrinkage of cells.
ii. Hypertrophy- increase in the size of cells to result
in enlargement of the organs.
iii. Hyperplasia- increased number of cells in an
organ or tissue.
iv. Metaplasia- transformation or replacement of one
adult cell type with another.
 VPT 302
•When cell fail to adapt, they undergo certain changes
called cell injury. The cells so affected may or may not
recover (Reversible or irreversible death)
Causes
•Anoxia (O2 deprivation)
•Physical agents
•Chemical agents
•Injection agents
•Immunological reactions
•Genetic defects
•Nutritional imbalances.
MORPHOLOGY OF CELL INJURY
Reversible.
•Cellular swelling and vacuoles formation (Hydropic
changes)
•Changes at this stage are better appreciated by the EM
showing blebbing of the plasma membrane, swelling of
mitochondria and dilatation of endoplasmic reticulum
(ER)

Irreversible (NECROSIS)
*Irreversible changes produced by enzymatic digestion
of dead cellular elements, denaturation of protein and
autolysis (by lysosomal).
*Changes are seen in the Nucleus and Cytoplasm.
 VPT 302
Mechanisms of cell death
Certain biochemical events that take place in the process
of cell death include:
•ATP depletion
•Loss of calcium homeostasis and free cytosolic calcium
•Free radicals: superoxide anions, hydroxyl radicals,
hydrogen peroxide
•Defective membrane permeability
•Mitochondrial damage
•Cytoskeletal damage
•APOPTOSIS (Necrobiosis)
- vital process that helps eliminate unwanted cells.
-An internally programmed series of events effected
by dedicated gene products.
-Removal of excess cells in developing embryo
LESIONS
– Characteristic changes in an organ produced by a
disease

Pathognomonic lesion: a change which is

specifically characteristic of a disease e.g. Negri
bodies for Rabies virus in neurons
NECROSIS
The local death of cells or tissues within the
living organism. This should be distinguished
from the term necrobiosis which is a
physiological death: natural death of a cell at the
end of its lifespan e.g. superficial layers of
epidermis or epithelial cell of the intestinal
tracts.
Death – ceasation or extinction of life.

Microscopic Features of Necrosis:

•Nuclear changes
•Cytoplasmic change
•Other change
GROSS CHARACTERISTICS OF NECROTIC TISSUES
•Loss of colour – becomes paler if not filled with blood
- black if filled with haemolysed blood.

•Loss of strength [tensile strength] – inability to

withstand pressure (liver, lungs) or stress (intestine).

*Development of putrifaction when exposed to

saprophytic organism (saprophytes) e.g. gangrene or
PM autolysis.
Difference between Necrosis and Postmortem Autolysis
Microscopically:
•Presence of both normal and dead tissues on the
same field.
•Necrotic tissues normally act as irritants to the
body, therefore there is normally a zone of
inflammatory reaction (cellular response) if left on
the body.
•Erythrocytes in the blood vessels are normally
bright red. But at postmortem, rbc usually undergo
lysis (haemolysis).
Note: The GIT b/c of the bacterial content is about
the fastest to undergo PM changes. The liver and the
CNS also quickly undergo postmortem changes.
CAUSES OF NECROSIS
1.Poisons: substances that produce injury when taken
into or applied to the animal body.

2.Lack of proper blood supply: cuts down the supply of

nutrients and O2 e.g. thrombi (from emboli),
ligatures, compressions of blood vessels by
tumors.
•CAUSES OF NECROSIS CONTD-
3. Lack of nerve supply – e.g. in Sweeney-shoulder lameness
in those associated with atrophy and necrosis of the
(supraspinatus/infraspinatus) muscle of the scapula.

4. Pressure – e.g. decubitus (Bed sore) in animals: long

continued pressure from adjascent tumous and abscesses,
recumbency, sites of bandage/casts.

5. Thermal mechanical (physical) injury – most severe in 3rd

burns, freezing, rays: sun, uv-light; accidental blow of a
hammer, heat – coagulation of protein, cold – bursting of
membranes, slogging of blood supply.
DIFFERENT TYPES OF NECROSIS
As a result of cell death the tissues or organs display
certain macroscopic changes:
•1. Coagulative N: the outline of the dead cells are
maintained and the tissues is somewhat firm. e.g.
Myocardial infarction.
•2. Liquifactive N: the dead cells undergo disintegration
and affected tissue is liquefied. e.g. cerebral infarction
•3. Caseous N: a form of coag. N. (cheese - like). e.g.
tuberculosis lesion.
•4. Fat Necrosis: Enzymatic digestion of fat. e.g.
necrosis of fat by pancreatic enzymes.
•5. Gangrenous N: Necrosis (secondary to ischemia)
usually with super imposed infection. e.g. necrosis of
distal limbs, usually foot and toes in diabetes.
ZENKER’S NECROSIS: Zenker’s degeneration
Occurs only in striated muscle (Myocardia and skeletal)
It is a coagulation of the proteins in the cytoplasm of striated
muscles.
Microscopically:
•Swollen fibers, homogeneous and hyaline in texture
•Acidophilic sarcoplasm (Reddish H&E)
•Small and dark nuclei (pryknotic)
•Loss of cross striations in fibre
Grossly – White or pale muscle: shiny and swollen
Aetiology:
•White muscle disease condition e.g. Vit E and Selinum deficiencies
•Infectious diseases like: foot and mouth disease (FMD) which is a
viral disease.
Significance:
-Fibres may regenerate by proliferation of the sarcolemma nuclei.
-Necrotic area may undergo calcification
Biochemical Diagnosis of Necrosis
Following necrosis, soluble substances are circulated
into the body e.g. enzymes/proteins, ions
•could specifically indicate areas of necrosis e.g.
Alanine aminotransferase (ALT) is highly
concentrated in hepatocytes.

Aspartate aminotransferase (AST) is also high in

striated muscles (myocardium and skeletal) and in
liver cells

High level of creatinine phosphokinase will indicate

kidney damage.
OUTCOME OF NECROSIS
•Liquefaction
•Formation of cyst-like accumulation.
•Liquefaction and abscess formation
•Necrosis area may be encapsulated without liquefaction
•Desquamation (sloughing)
•Repair may take place in form of replacement.
•Calcification
•Invasion by anaerobic organism leading to gangrene
•Atrophy of the tissue.
GANGRENE
This is a clinical term applied to any black and fowl swelling
area that is in continuity with living tissues. It is liquefied necrotic
area + invasion of saprophytes (putrefactive bacteria).
Two types of gangrene: wet and dry gangrenes.
Causes:
i.In the extremities and intestines, interference with blood
supply is the major cause.
ii.In the lungs and udder, toxic products of highly lethal bacteria
are the causes.
SIGNIFICANCE OF GANGRENE: Because gangrene can

spread and the bacteria and toxin produced from the

decomposition can disseminate to other parts

efforts should be made to stop the process by

amputation, and surgical removal of affected parts

e.g. intestine.
INFARCTION: An infarct is a localized area of necrotic tissue
resulting from deprivation of blood supply (Ischaemic). The
resultant necrosis is usually a coagulative type and is common
with areas supplied with single end-arteries e.g. kidney, brain.
•Recent infarcts are usually haemorhagic or red infarct due to
back flow of blood from efferent veins into the capillaries of the
necrosis area.
•Others are pale or anaemic infarct depending on their age. The
paleness or redness also depends on the denseness or
perviousness of the tissues.
Types of Infarcts

•Renal Infarcts: usually conical with the apex at the cortico-

medullar junction. Causes: Chronic valvular endocarditis is a
common cause in dogs and pigs. It is always an anaemic type.
•Splenic infarct: mainly shallow, subcapsular infarct that is
haemorrhagic in nature. It is seen in hog-cholera (viral disease)
of pigs.
•Infarct of brain – usually anaemic, and quickly liquefied.
•Intestinal infarcts are usually haemorrhagic and deadly. It
usually involves a food length of the intestine. Caused by
strangulation of the intestine e.g. in a hernia sac.
•Myocardial infarcts: not common in animals. Usually red or
gray.
•Pulmonary infarcts – usually heamorrhagic.
•Hepatic infarct is rare but could occur if hepatic artery
is blocked. In cattle, hepatic infarct can occur in
Clostridium haemolyticum infection (Bacillary
haemoglobinuria).
•Mammary gland infarcts are common in mastitis
caused by highly virulent streptococci producing
necrotizing toxins.

Significance of Infarction
•Area may undergo gangrene formation
•Area may undergo abscess formation
•Area may undergo scar formation
•There could be loss of function e.g. paralytic stroke as in
the brain infarct.
DEGENERATIVE CHANGES
Regressive Change
Reversible disorders of cells/tissue which
are not dead yet, but may lead to necrosis
if insults are not removed. Cells may
recover if interference to the cells is
removed in time.
•Proteineous Changes
I.Cloudy swelling: This is the term used to describe cells
that are slightly swollen due to changes in function of the
cell membranes and membranes of the organelles e.g.
changes is Na+ - K + pump lead to intracellular
concentration of Na2, Ca2+ and decrease in K+. This will
lead to influx of water.
II. Hydropic degeneration (Ballooning
degeneration / Vacuolar degeneration)
i.e. presence of water in the cytoplasm of the cell
e.g. epithelial cells. The change is seen as clear
space surrounding the nucleus. Aetiology :-
Nutritional and serenity, Infection – Pox and
FMD viruses.

III. Hyalin degeneration – Deposition of

homogenous, translucent, eosinophilic, solid,
dense smooth materials (protein)
intracellularly. It is associated with nutritional
deficiencies: e.g. Vit. E def.
AMYLOIDOSIS
This is a degenerative change.
Amyloid are amorphous, eosinophilic
homogenous proteinous materials (a glyco-
protein) initially deposited extracellularly under
the epithelium of the blood vessels. Amyloid is
made up complex structures of filaments or rods.
With Congo-red it stains pink or orange to
orange-red with bifringent light-green under
Polaroid microscope.
CLASSIFICATION OF AMYLOID
I. On the basis of staining with Congo-Red
•Typical – Stains with Congo-red.
•Atypical – does not stain with congo-red
II. IO amyloidosis – no anticident or co-
existence with any disease.
2O amyloidosis – following chronic disease: TB,
Osteomyelitis, rheumatoid arthritis, (characterized
by increase IgG); hyper- immunized horse.
III. Associated with myeloma (Plasmacytoma):
Production of Bense-Jones Protein:(75
Immunoglobulin man).
IV. Isolated organ as in senile human
Clinico- pathological features of Amyloidosis
Usually a progressive phenomenon – spleen, liver &
kidneys, lymphnodes and adrenal
1. Renal: commonest and most serious type of
amyloidosis.
Initially in the glomeruli in general; to tubules & the
medulla in cattle & cats - Io site is intersititial. This
leads to PROTEINURIA & casts
•2. In dogs - pulmonary artereo-thrombosis
•3. Hepatic amyloidosis – in Spaces of of disse. No serious
dysfunction noted.
•4. GIT amyloidosis – e.g. In monkeys (macague) – in lamina
propria – leading to blunting of the villi & atrophy of crypts ->
malabsorption.
•5. Splenic amyloidosis – around the central arteries of the
splenic corpuscles
-> follicles – appearance of tiny white nodules (grains) ‘Sago’
(Tapioca droplets). In the medulla area it gives the appearance
known as ‘Lardaceous spleen’ – lardosis
•6. Isolated Organs
– Islet of Langerhans – pancreas in Cat family ->

diabetes mellitus;
- myocardium – man & mice.
– Respiratory tract – horse & man as tumor like
deposit.
Aetiology: Usually due to chronic activation of
the Ag-Ab system as in the Io amyloidosis.

Grossly: hard opaque white deposit, mainly in

spleen. Enlarged liver with pale colour
Microscopically: Stains pinkish or purplish pink with
H&E stain (Haematoxylin & eosin). Specific stain:
+Cresyl violets gives deep red;
+Congo-red gives pink. – Sharp demarcation as against
gradual one in hyaline.
+Aqueous solution of I2 on slide of fresh tissue gives
brown.
+Addition of dil. H2SO4 following I2 solution will convert
brown to give blue colour.
+Periodic acid-Schiff (PAS) gives violet.
+Thioflavin T, gives green birefringence under UV light.
MUCINOUS DEGENERATION
•Excessive accumulation of mucin in the Epith. cells of
mucous membranes such as lining of the G.I.T. & Resp.
Tract.
-Aetiology: - mild irritants, mechanical, chemical
infections.
-Mucin stains blue with H&E.
Pseudomucin (by adenomas & cyst adenocarcinoma) –
pink with H&E.
PAS – mucins – Rose to pink or purple-red.
Mucicarmine stains mucins – Rose to pink or purple –
red
MUCOUS DEGENERATION
Mucous degeneration (Myxomatous
degeneration) or mucoid atrophy of fat – in
tissue with ct. + fat (adipose ct.) – around
the coronary grove of the heart, omentum
and mesentery.
Microscopically – proliferation of ct. of
embryonal xtics: hyperchromatic nuclei,
ovoid or spherical nuclei.
Grossly: Translucent and watery.
Aet: Mal-nutrition, toxaemia,
• ill-health indicator to meat inspectors.
 GOUT
•Disturbance of purine metabolism
•Formation of crystals of Ca+ & Na+
•Urates resulting in the tissues.
•Tophi – deposits of gout in tissues.
•Occurrence – man, birds, dogs & cats
•Birds:-
•Articular gout
•Visceral gout.

•Articular & peri-articular spaces and subcuitis result in

friction, irritation & pain & inflammation, Swollen joints.
White chalky mass in the joint and ulceration of the
surround skin.

Visceral gout:
•Metallic sheen (gloss) on the serous surfaces of the
viscera; deposit of crystals in ureters (kidney), serous
surfaces of the liver, pericardium and airsacs.
Aet: a) Avitaminosis A, b) too much of protein
(imbalance) in diet.
DISTURBANCES INVOLVING CARBOHYDRATES
Glycogenic Infiltration:
Glycogen is normally found in the liver and muscles.
Pathologically: found in the epith. cells lining, straight
tubules, Loop of Henle of kidney. Also found in
inflamed tissues.
Microscopically:
Clear spaces around nuclei
Fixing should be done with a non-aqueous fixative e.g.
absolute alcohol or Carnoy’s fixative to demonstrate
glycogen.
Stains: Best’s Carmine Stan gives Bright-pink.
Grossly – usually not visible.
Significance: indicative of cellular injury.
DISTURBANCES INVOLVING FATS (FATTY CHANGE)
Intracellular accumulation of lipids (usually neutral fat)
in organs: liver, kidney and heart.

Microscopically: appear as vacuoles (clear, unstained

spaces) spherical spaces.

Glossly: Organs are enlarged, tan or yellowish in colour,

- light and friable, float in water.

Aet: interference with transport or metabolism of fat or

protein synthesis.
Fatty change seen in:
•A. Liver: -periportally – in poisoning
(haematogenous) – centro-lobular – as in iron def.
(anorexia)
•B. Kidney – proximal convoluted tubular (PCT)
and Ascending loop of Henle.
•C. Heart – fine droplets in the myocardium.

The 3 organs (A-C) could be involved

simultaneously as in ketosis (Diabetes),
pregnancy toxaemia (Ewes with Twins)
Also in rabbits & guinea pigs with more than 2
feotuses.
Significance/consequences of fatty change
It is reversible if insults are removed
Hepatic necrosis may follow if persistent
Fat cells may be released as emboli
Liver can rupture
Stroma Fatty Infiltration – within the normal ct.
of organs like pancreas and heart.
Extracellular accumulation of lipid – outside
cells in some situation: cholesterol released from
some necrotic cells or pooled from lipo-protein
and deposited in crystalline form in areas of old
haemorrhage.
CHANGES INVOLVING Ca2+ METABOLISM
Ca++ salts get deposited in tissue (abnormally)
other than the bone and teeth – as Ca – carbonate,
- phosphate, - hydroxyl-apatite, - mixture with
iron-salt resulting in Mineralization
(calcification when Ca++ salt only)
Calcification
•a.Dystrophic calcification – deposition of Ca++ in dead or
dying tissues. Not linked with increased Ca++ concn.
•b. Metastatic calcification
Result from pptn of Ca+ in hypercalcaemia
FIBRIN
Fibrin is a proteinaceous substance normally present in
•Blood clot from fibrinogen,
•In fibrinous exudates.
Microscopically :pink, interlacing materials with bead-like
materials (spongy- like) – with karyolysis results in blueish-tinct
b/c it will absorb the released chromatin from the environment.
Grossly: - stringy material, dull white – usually mixed up with
other exudates and dead tissues.
Consequences: It can lead to:
•Thrombi leading to regional necrosis [infarction] due to
ischaemia. – ischaemic necrosis.
•Fibrin could be liquefied leading to autolysis
•Could attract fibroblasts leading to growth of fibrous c.t. –
organization: resulting into thrombi.
FIBRINOID DEGENERATION
Occur in collagen disease of man and animals.
Aet: Ab – Ag reaction e.g. rheumatic fever.
DISTURBANCES INVOLVING PIGMENTS
Pigment are in 2 main groups:
•Exogenous,
•Endogenous.
The other group are the pigments haematogenous
CLASSIFICATION OF PIGMENTS
I.Exogenous pigments – formed outside the
body:
a) – Carbon – anthracosis
b) – dust – silicosis, siderosis, asbestosis
c) – metals – argyria, lead, bismuth
d) – Tattoos
e) – Kaolin
f )– Carotenoids (lipochromes)
Exogenous pigments – those that may enter through the
respiratory tracts – found in the lungs and contiguous
lymph nodes draining the lungs.
•Anthracosis - presence of carbon particles (deposits) in
tissues e.g. in smoky cities.
•Pneumoconiosis: accumulation of dust in the lungs
a.Silicosis – due to inhalation of silicon dioxide, as seen in
people blasting rocks.
b.Siderosis: inhalation of iron dust/iron dust (iron oxide
or haematite from mines). It does not elicit inflammatory
reaction but always accompany silicosis.
c.Asbestosis: from asbestos factories
II Endogenous pigments – formed inside the body
•Phenolic pigments
1 – melanin
•Haematogenous pigments
1 – Haemoglobins – methaemoglobin
2 – haematin (acid-haematins) e.g. acid formalin haematin
3 – parasitic – haematin in malaria, fascioliasis
4 – Haemosiderin e.g. Heart failure cells
5 – Bile
6 – porphyrins – congenital & porphyria photosynthesitization
•Lipogenic pigments
1 – tissue lipofuscins
2 – ceroid
3 – Vit. E def. pigments
•Miscellaneous Pigments
1 – Ochronosis pigment [hereditary disease]
2 – Dublin-Johnson pigment [hereditary disease]
3 – Cloisonné Kidney
Silver – Argyria-disorder involving silver. Occurs as a
result of men treated with silver compound that are
deposited under the skin (upper corium) giving grey
colour
Microscopically – insoluble albuminate which is brown-
black in fibrous ct. no cellular injury or reaction.

Lead – prolonged ingestion or assimilation of lead (Pb)

leads to formation of blue-black colouration of the teeth
top and long bones (x-ray)
Kaolin – China clay made up of hydrated
aluminium silicate (Kaolinite) and other elements
could be present.
– incriminated to cause pneumoconiosis
(Kaolinosis) in man leading to granulomatous
reaction and pulmonary scarring; subcutaneous
granulomas in the pharyngeal and neck tissues in
animals treated for GIT diseases. Amorphous
materials in macrophages and as crystals.

Tattoos – done usually with Indian or China ink.

No tissue reaction.
CAROTENOID PIGMENTS or lipochrome
pigments
Fat-soluble greenish-yellow pigments of plant
origin e.g. carotene A, carotene B and
xanthophyll.
Not to be confused with ‘Wear and Tear’ pigments
‘Lipofuscin’ or Pigment of Brown atrophy.
Carotenoid pigments are normally present in
epithelial cells of adrenal, corpus luteum, testis
and seminal vesicle, Kupffer cells of the liver,
ganglion cells and egg yolk and adipose tissues of
horse and cattle. The subcut gets yellow or
greenish yellow coloration.
ENDOGENOUS PIGMENTS
•Autogenous pigments of which Melanin is the most
important. They are formed within individual cells.
Phenolic pigments.
•Melanin – normally found in the colour of the skin, hair
and Iris and retina of the eyes.
•Some quantities are also found in the anterior part of
the brain (sudstantia nigra).
•Primarily located in stratum germinativum.
Melanin is formed from Tyrosinase – melanin under the
influence of hormones (Melanocyte stimulating factors): -
α-MSH and β- MSH by the pituitary gland. Melanin: In
black people – S. germinativum and inner layer of skin –
In albinos – absent in skin and hair follicles.
Pathologically
•Melanoma – tumor, that could be malignant and found
in muco-epithelium
•Melanosis – deposit of melanin in various organs e.g.
lung, aorta. No tendency towards neoplasm.
•Albinism – pathological absence of melanin. The
melanocytes are unable to produce melanin. Cu is an
important component of tyrosinase needed in conversion
of tyrosine to – melanin. [stain] – Fontana-silver Stains
melanin black
•Microscopically – Dark granule in melanophores (MQ
with engulved melanin)
Significance
•Melanin is protective against sunburn
•Melanosis is not harmful
•Melanoma affects the functions of the organs concerned.
HAEMATOGENOUS PIGMENTS
Haemoglobin : Haeme + globin
Free Haemoglobin if there is breakdown of rbc
converted to Haemoglobinaemia and Haemoglobinuria
If haemoglobin escapes from vessels after death to stain
the tissues – ‘Post-mortem imbibition’ of (of perivascular
tissues). Formation of met-haemoglobin, in hb poisoning,
leads to oxidation of Fe2+ to Fe3+ - Chocolate brown
colour. {Nitrite, chlorates and sulphates = poison}.
Nitrite poisoning – Ruminants break nitrate to nitrite –
chocolate – brown colouration of lungs, kidney, muscles
and mucons mbr.
•Carboxy – Haemoglobin – occurs in cobalt poisoning –>
bright cherry-red blood.
•Sulphur – haemoglobin: This is a reduced haemoglobin
+ inorganic sulphide.
Sulphur – Methaemoglobin – gives greenish
decolouration of the carcass at post-mortem
examination.
•Acid formalin haematin pigment – formal-precipitated
haemoglobin: seen adj. to the peptic or duodenal ulcer
b/c of the presence of HCL (Hydrochloric acid haematin).
Here the Fe is not stained.