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GENERAL PATHOLOGY
CHAPTER 2: DEGENERATION AND NECROSIS
Clinician – end product of a medical curriculum
- function is the diagnosis and treatment
of disease
- learn the normal development,
structure and function of the body
Pathology – study of malfunction and disease of
structural and functional changes in cells,
tissues, fluids and organs.
- cornerstone, because the clinician
cannot rationally diagnose and treat
without understanding the disease
process with which he is dealing.
Sick – some part of the body is not functioning
properly, and it is expected that with proper
diagnostic procedures the problem may be
found and treated.
Pathology – study of the molecular, biochemical,
functional and morphological aspects of
diseases in the fluids, cells, tissues and
organs of the body.
Pathogenesis – the sequence of events from the
point at which the lesion began through its
entire development.
Etiology – cause of the problem / disease.
Theory of pathology – master the terminology by
learning the definitions, uses and limitations
of the language of pathology in its role in
the description of lesions and their
pathogenesis and etiology.
Practice of pathology – involves being able to
describe lesion
- to recognize the
disease process
explain how it might
have occurred
“the theory is dangerous without the
practical ability”
-
Categories of lesions
1. degeneration and death of cells
2. circulatory disorders
3. inflammatory and repair
4. disturbance of growth
5. development of cancer
Objective of general pathology
- learn the basic lesions and pathogenetic
mechanisms associated with disease
processes so that they can be applied
later to the study of the lesions and
pathogenesis of specific disease entities
in special pathology.
Pathologist – individual who devotes his efforts
primarily to the study of disease processes
Diagnosis
a. morphological (naming the lesions)
b. etiological (naming the cause)
c. definitive ( naming the specific disease
entity involved)
Veterinarian – diagnose, treat, prevent and control
animal disease
Diagnosis – ability to recognize lesions in the live or
dead animal, to understand the
pathogenesis and, through these, to make
rational conclusions and recommendations
for treatment, control and prevention
Prognosis – expected outcome of disease (recovery
or death)
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DEGENERATION
(abnormal morphological change)
Indicates:
1. temporary functional changes or
adaptations
2. progression toward death of the cell
degeneration – reversible if the functions returns to
normal
degenerative lesion = ‘osis’
General Intracellular Degenerative Changes
1. exocytosis / exotropy – normal membrane may
bud off as external blebs
2. endocytosis / esotropy – particles and fluids
may be taken in by internal blebs
3. heterophagy – removal of particles brought into
the cell
4. autophagy – removal of degenerate component
with the cell
5. autolysis – internal release of the enzymes from
lysosomes is likely to be fatal of the cell
Externalization
Exocytosis – esotropy (reverse)
Budding – exotropy (addition/out)
reverse – addition of membrane
forward – subtraction of membrane
Internalization
Endocytosis – esotropy (forward)
Fusion – exotropy (addition/out)
Intracellular Degenerative Changes
1. cell swelling
2. degeneration involving fats
3. intracellular inclusions
CELL SWELLING
- most common and important response
to cellular injuries
- cells appear crowded
- diluted/indistinct appearance of
cytoplasm
- injury to cell results in disruption of the
control mechanisms for the osmotic
gradient at the cell membrane
-
a) Cloudy swelling – old term for
swollen cell
b) hydropic degeneration (ballooning
degeneration)
- present of clear vacuole in the
cytoplasm
- associated with epithelial
lesions (eg. Inclusion bodies)
DEGENERATION INVOLVING FAT
1. fatty deg. – abnormal accumulation of fat in the
cytoplasm of parenchymal cells
- liver is best known location of the
lesion
GROSS appearance – fatty liver is yellow
MICROSCOPIC – fat is a large, clear,
discrete droplets with foamy appearance
2. fatty infiltration
- lesion is the presence of fat in adipose
cells that accumulate in tissue in which
they are not normally present (fatty
replacement)
Steatosis – large areas of muscle have a pale or
mottled color due to fatty infiltration
Steatitis – inflammation of fat (yellow fat disease)
Steatorrhea – fats discharge with feces
INTRACELLULAR INCLUSION
1. hyaline droplets – small eosinophilic structure in
the cytoplasm of cells (hyaline droplet den.)
2. pigments
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Extracellular Degeneration Changes
1. Hyalinization / hyalinized – describe the change
from normal to variable degrees of smooth
eosinophilic appearance.
Eosinophilia – indicates presence of protein
Hyalinization – thickening of basement
membranes
Hyaline casts (urine sediments)– protein
leaks through glomeruli
Hyaline thrombi – smooth, shiny red
capillary thrombi
2. Firbrinoid – amorphous, bright, eosinophilic
material found particularly in the walls of blood
vessels
Fibrin – major component along with
serum
proteins,
particularly
immunoglobulins
Lesion involves antigen-antibody complexes
and complement
6. Amyloid – amorphous eosinophilic material that
accumulates in tissue, particularly in basement
membrane.
Amyloidosis – amyloid present in tissues
(walls of blood vessels) and cause
major
functional
and
morphological changes.
Primary – result in the production of
immunoglobulin-amyloid
precursors by abnormal
plasma disease
Secondary – occurs in chronic
infectious disease in which
immune system has been very
active for a long period
making immunoglobulin
4. Cholesterol clefts
Cholesterol – may collect as crystals in
tissue after severe tissue damage or
hemorrhage
Xanthomatosis – massive accumulation of
lipids in macrophages
Xanthomas – lipid tumor in skin
7. Calcification – deposition of calcium salts in soft
tissues
Classification:
1.
dystrophic – implies tissue
damage, degeneration or death
of cells or denaturination of
protein in tissue, which allows
the salt of calcium to
precipitate.
2. Metastatic – occurs as a
deposition on basement
membrane and elastic fibers in
several organs, particularly
arteries, and implies high level
of serum calcium, excess Vit
D or hyperparathyroidism.
5. Corpora amylacea – circular laminated
concentration found in glandular tissue or free
in secretion
Calcinosis – extensive metastatic calcium
Calciphylaxis – widespread deposition of
Calcium in tissue treated with Ca sensitizer
3. Gout – disease that occur when uric acid and
urates crystals are deposited in tissue owing to
defects in purine metabolism
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NECROSIS
(rapid death of a limited portion of an organism and is considered
to be the final stage in irreversible degeneration)
APOPTOSIS – genetic program / release of
endonuclease that cause natural cell death
- physiologic / pathologic
necrobiosis – term used for the entire process of
degeneration and death of cells
- tissue was dead prior to the time of
removal from the live body or prior to
the time of the animal’s death
- rapid death of a limited area of tissue
lesion – change in structure and impairment of
function
Cellular Characteristics of Necrosis
A. Nuclear Change
1. pyknosis – condensation of nuclear
chromatin into a dark, round,
homogenous mass smaller than in a
normal nucleus.
2. Karyorrhexis – shattering of the
nucleus into numerous pieces
3. Karyolysis – dissolution of nuclear
chromatin, leaving a hollow, large,
round, ghost form of the nucleus.
4. Anucleation - Absence of the nucleus
B. Gross Characteristics of Necrosis
1. loss of color (paleness)
2. loss of strength
3. definite zone of demarcation (between
necrotic and normal)
-
the recognition of necrosis in gross
lesions will be one of the most difficult
practical aspects of general pathology
to master.
C. Cytopalsmic Changes
1. increase acidophilia
2. lost of cytopalsm
TYPES OF NECROSIS
1. coagulative – ischemia , infarction
2. liquefactive – bacteria (lysosomal enzyme)
3. fat necrosis – pancreatitis
4. caseous – TB
5. fibrinoid – autoimmune disease
6. gangrene
coagulation necrosis – area of necrosis in which the
gross and microscopic architecture of the
tissue and some of the cells are
recognizable.
Caseation necrosis – is manifested by loss of
recognizable architecture and will contain
combinations of much dark nuclear debris
and amorphous eosinophilic cytoplasmic
debris, perhaps mixed with components of
blood clots, hemorrhage, thrombi and
calcification.
Coagulation – caused by acute anoxia
Caseation – caused by severe local
destruction (cheesy)
Liquefactive necrosis – present of semi-solid or fluid
mass
Malacia – softening (necrosis of nervous
tissue)
Focal necrosis – implies numerous small
white foci in random distribution
in the liver or kidney or other
tissue.
Erosion – shallow area of necrosis confined
to epidermis that heals without
scarring
Ulcer – excavation of s surface produced
by necrosis and sloughing of the
necrotic debris
(wound that never heal)
slough – necrotic tissue in the process of
separation from viable tissue and
implies a process of shedding
sequestrum – isolated necrotic mass
sequestration – process of isolation
(infacts)
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Fat necrosis – occur in abdominal cavity or under
the skin
- the release of fat into connective tissue
induces a marked inflammation and
fibrosis
- occurrence of cholesterol cleft and
calcification
Gangrene – saprophytic bacteria grow in necrotic
tissue
Dry gangrene – occurs in skin in which
there is little fluid in the necrotic
tissue
- because of evaporation and
drainage;
but
there
are
saprophytes
- ischemia, cause of necrosis
(decrease blood flow)
Wet gangrene – black in color, contains gas
bubbles
and
has
much
hemorrhage and edema
Requirement of Gangrene:
1. necrosis
2. putrefaction of bacteria
AUTOLYSIS – self-digestion by the tissue enzymes
Postmortem Changes; varies
1. cause of death
2. air temperature
3. temp of the body at the time of death
4. amount of time since death
5. presence of bacteria in the tissue
Rigor mortis – stiffening of all muscle after death
and relates to contraction of muscle fibers
as ATP decreases
Algor mortis – gradual cooling of the body after
death
Livor mortis – gravitational settling of blood to the
down side of the animal / seepage of blood
* pseduomelanosis – darkened coloration of
tissue due to lividity
Postmortem decomposition involves
1. discoloration
2. softening
3. distention
4. displacement of tissue
1. Discoloration – result from the breakdown of
hemoglobin and the action of bacterial hydrogen
sulfide on hemoglobin
 imbibition – turning of red color of
tissue due to lysis of erythrocytes with
permeation of released hemoglobin to
tissue
2. Softening – caused of autolysis with assistance
from saprophytic bacteria or perhaps the normal
bacterial flora of the tissue
3. Distention – fermentation with gas production
in the digestive tract
- causes pressure effects in other viscera
- blood is pushed out
gas bubble – present in autolysis and
putrefaction
4. Displacement – occur in the form of twists in
the intestine, intussusception or herniations
 hemorrhage – present before death
(ante-mortem)
 no hemorrhage – post mortem tear
Bacterial Flora
1. contribute to autolysis and putrefaction
if multiplication of organisms occur
before death
2. must be considered in interpreting the
result of bacterial culture of tissue from
dead animals
Pigmentation
1. exogenous
2. endogenous
Exogenous Pigmentation
1. pneumoconiosis – occupational pathological
pigment, inhalation of compound in
minerals/dust
2. Anthracosis – inhalation of carbon compounds
Endogenous Pigmentation
- related to melanin
- derived from lipid, hemoglobin or
porphyrins
1. melanin – normal pigment made by melanoblast
and melanocytes
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melanin-producing cells – derived from
neural crest tissue
melanosis – present of melanin in an
abnormal location, such as on the
pleura, meninges or heart, and is
congenital mislocation of melanocytes.
Melanomas – tumor of melanoblasts
and melanocytes
Amelanotic melanoma – tumor having
no / little melanin
Albino – complete absence of melanin
is a congenital defects
DOPA test (Dihydroxylphenylalanine
test)
- test used to identify the cells that
have the capability to make
melanin
Melanophores – macrophages that pick
up granules of melanin
Lipid prigments – results from oxidation and
polymerization of unsaturated lipids
Ceroid – found in macrophages following tissue
damage or hemorrhage or both in which
lipids have become free in the tissue
Lipofuscin – found as yellowigh-brown granules in
the cytoplasm of affected parenchymal cells
- reflection of the content of autophagic
vacuoles that contain partially
metabolized lipid
Vitamin E – accentuate lipofuscin formation
(Vitamin E pigment)
Carotenoid – yellow color in fats
Hemoglobin and Porphyrin Derivatives
1. Hemoglobin – reddish-orange color
2. Hemosiderin – brown color, contain iron
(hemosiderosis)
Hemochromatosis – kidney becomes
discolored black due to excess
accumulation of non-iron staining brown
pigment in hepatocytes and renal tubular
epithelium.
3. Hematin – result from the actual of acid or
alkali on hemoglobin. Formed on tissues when
exposed to acid / alkali after death
(hematin is very common as “formalin
pigment” when unbuffered formalin is
used for fixation).
4. Bilirubin – formed from the tetrapyrrole ring
structure of hemoglobin when iron and protein
have been removed. Normal by-product of
hemoglobin breakdown.
 Conjugated bilirubin – cannot pass in
the glomerulus
 Biliverdin - birds
5. Jaundice (icterus) – bilirubin present in the
plasma in excess and all tissues are stained
yellowish-brown.
Types of Jaundice:
1. Prehepatic – arise from acute
hemolytic episodes that send
bilirubin to the liver in larger
quantities than can be
proceed.
2. Hepatic – direct damage to
liver cells and release of
conjugated and unconjugated
bilirubin into the blood.
3. Posthepatic – bilirubin has
passed through the liver cells
but is blocked from the entry
into the intestine.
6. porphyrins – when accumulate in the blood may
cause pigmentation of tissues along with
jaundice and also photosensitization.
Porphyria:
1. congenital – metabolic defect
in the steps of breakdown of
porphyrins
2. hepatotoxic – phylloerythrin, a
metabolite of chlorophyll, that
has photosensitzing property.
It accumulates when toxic
damage to the liver impairs its
normal degeneration.
3. Primary – caused by plant that
contain compounds directly
photosensitive by ingestion
without
hepatic
injury
(Fagopyrism & Hypericism)
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Sequelae of necrosis
1. Calcification
2. Localization – sequestration, resorption (granulation
tissue – scar)
3. Lysis – cyst, cavity
4. Secondary infection – abscess, gangrene
CHAPTER 3: CIRCULATORY DISTURBANCE
3. acting as a source of reserve body
* lesion related to blood vessels and blood that are
protein and serving as carriers of many
common to all tissues in various kinds of
substances, including lipids, hormones,
tissue injury and that may be observed in
vitamins, drugs
the live or dead animal
hemorrhage – RBC / blood may leave the blood
vessels
hyperemia – lesion in which excess blood may be
drawn into an area
congestion – blood may passively accumulate in an
area
edema – excess fluid accumulate in tissue
ischemia – blood kept from reaching an area of
tissues
infarction – process where the tissue undergoes
complete ischemia and become necrotic
thrombosis – blood clot within blood vessels
embolism – solid structure may float in the blood
vessels
shock – generalized failure of peripheral circulation
HEMOSTASIS – blood clotting
a. intrinsic clotting system – all factors are
present in plasma
b. extrinsic clotting system – factors from
outside the plasma
 both system function – more fibrin is
produce than intrinsic system alone
 disease state: fibrinogen level increase
in plasma
Liver – only source of
a. fibrinogen
b. prothrombin
c. albumin
d. a & b globulins

gamma globulins – from lymphocytes
and plasma cells
Functions of plasma protein:
1. maintaining osmotic pressure
2. acting as buffers
* complement systems is composed of
normal plasma proteins
HYPEREMIA – amount of blood flow usually
corresponds to the amount of work being
carried out and so will vary in different
areas at different times. Functional reserve.
- tissue becomes red because of the
increased number of RBC present, and
the blood present is arterial blood
therefore well oxygenated.
- ACTIVE PROCESS, all capillaries
would be opened, dilated and filled
with RBC
- Examples are inflammation, blush
(nervous control / physiologic – release
of vasoactive substance, such as
histamine and lactic acid.
VENOUS CONGESTION – congestion implies
that the flow of blood leaving an area is
impeded and the blood therefore
accumulates in the venous circulation.
PASSIVE PROCESS.
- caused by physical obstruction of either
small or large vessels or failure of forward
flow, as in heart failure.
 cyanotic – poorly oxygenated venous
 cyanosis – deficiency in hemoglobin
(bluish color)
a. Localized congestion – strangulated
piece of intestine in which the
compression on the vessels is such that
arterial blood still gets through the
muscular arteries but the pressure on
the thinner-walled veins restricts the
outflow and venous blood accumulates.
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b. Generalized congestion – involves the
central circulation of the heart and
major vessels (including the lung), since
all the blood must flow through these
organs.
Causes:
1. flow may be obstructed
2. heart may too weak to pump
adequately or the blood may not
be returned to the heart for
pumping
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right-sided HF – impaired right side of
heart/lung (blood accumulate in major
vein and liver)
Left-sided HF – impaired left side of
heart (blood accumulate in lung)
NUTMEG LIVER – chronic passive
congestion
HEMORRHAGE – RBC present outside the blood
vessels
a. vessels is physically damage (rhexis)
b. cells may pass through an intact
vascular walls by diapedesis
diapedesis – occur where there is increase venous
hydrostatic pressure in vessels that are not
broken but perhaps: (A) anoxic and not
functioning properly, (B) clotting
mechanism is defective.
Hemorrhage result in vascular damage:
inflammatory, necrosis, trauma, neoplasia
Petecchial hemorrhage – tiny pinpoints and
up to 1-2mm size foci
Ecchymotic hemorrhage – larger areas 2-3
cm size
Paint-brush – extensive
Purpura – clinical term applied to extensive
petecchial
and
ecchymotic
hemorrhage in serous and mucous
suface.
Hematoma – blood cells accumulate to
form lump
Massive hemorrhage into body cavity:
a. hemopericardium
b. hemothorax
c. hemoperitonuem
hemorrhage diathesis – mark bleeding
tendencies, clotting defect (congenital,
acquired)
EDEMA – abnormal accumulation of fluid in tissue
spaces,
- lesion, not a specific disease
Etiology relates:
a. hydrostatic pressure of blood
b. osmotic pressure of blood and tissue
fluid
c. permeability of capillaries
d. lymphatic obstruction
Acute – trauma or inflammation
Chronic – heart failure and renal disease
Main pathogenetic mechanism
1. Filtration – force that expels fluid from the
vessel is the hydrostatic pressure at the arterial
end of capillary minus the osmotic pressure of
the blood.
2. Absorption – force that draws fluid into the
vessel is the osmotic pressure of the blood
minus the hydrostatic pressure at the venous
end of the capillary
a.
hydrostatic pressure – influence mainly
at the venous end of the capillary
b. osmotic pressure – reduced plasma
protein levels
albumin – maintain osmotic
pressure (4x osmotic pressure of
globulin)
eg. renal edema / debilitation
edema
c. permeability – changes result from
direct damage (trauma, inflammation),
anoxia (heart failure. Eg. Inflammatory
edema
d. lymphatic obstruction – impedes
normal lymphatic drainage by pressure
or obstruction
Recognition of edema
 excess clear fluid
 fluid have yellowish tinge color (plasma
protein)
 dilation of lympahtics in tissue (no
protein present in the fluid, pinkstaining fluid-H&E)
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extent of vascular damage (indicate
color variation)
Anasarca – extreme edema of body (aborted fetuses)
a. pulmonary edema
b. gut edema (E. coli)
c. Malignant edema (C. septicum)
Fluid in body cavity
a. hydrothorax
b. hydropericardium
c. hydrocele
d. ascites
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protein is present in fluids
degree of coagulation occur
exposure to air
resulting in a yellow-white colored
coagulum in the fluid
Hydrothorax – arises from leakage of surface pleural
lymphatic vessels in very edematous lungs
- left-sided heart failure
ydropericardium – arises from excess flow of lymph
within the mycocardium, result of vascular
damage or degeneration in the myocardium
- mulberry heart disease in pigs
Ascites – chronic passive congestion or heart failure;
increase venous hydrostatic pressure in
abdomin
- chronic renal disease
- hypoproteinemia
- tumors implanted in abdominal cavity
carried to lymphatic vessels
THROMBOSIS, ISCHEMIA AND INFARCTION
hemastasis – clotting system, consist of the key
processes of vasoconstriction, clumping of
platelets and formation of fibrin
coagulation – only formation of fibrin
thrombus – solid structure formed in the blood
stream from the normal constituents of the
blood, process of thrombosis
- differ from extravascular and postmortem clots
- composed of platelets, fibrin and RBC
& WBC
intrinsic system – involves activation of the stepwise
series of enzyme reactions to form
thrombin
extrinsic system – involves contract of blood with
lipoproteins from tissue debris, called
thromboplastin
Causes of thrombosis
1. rate of flow and flow patterns (turbulence of
blood)
2. blood vessel wall
3. composition of blood itself
a.
rate of flow & turbelence. Mechanical factors,
fibrin, platelets and white cells account for the
white color of arterial thrombi
b. injury to the vessel wall. Platelet adhere
primarily to subendothelial structures
c. changes in the blood. Shock/toxemia, may
activate hageman factor or cause the platelets to
release thromboplastin, and cause blood to
become sticky.
Results of thrombosis
1. lysis – fibrinolysis
2. plasmin – component of serum, activated during
stress, infection/shock, released from injured
tissue
3. contraction – connective tissue and capillaries
will grow into it and form a permanent new
layer on the inside of the vessel
ISCHEMIA – local anemia or reduction in flow of
blood to an area and usually refers to the
flow of arterial blood.
- dependent on organ, the size of the vessel;
the degree of occlusion and the degree of
collateral circulation
partial ischemia – anoxia, hypoxia (not necrosis)
ANOXIA
1. stagnant – reduced flow of O2 blood
(shock & heart failure)
2. anoxic – insufficient O2 of blood
(severe pneumonia)
3. anemic – low hemoglobin or reduced
capacity to carry hemoglobin
4. histotoxic – inability of cells to use O2,
as in a toxic damage to cells
INFARCTION – acute ischemic coagulation
necrosis of an area of tissue
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Infarct – localized area of ischemic necrosis in a
tissue or organ
1. red infarct – leaking vessel of infarct in
the lung (most dangerous)
2. Pale infarct – blood supply is radial, as
in the kidney
* Venous infarction is more hemorrhagic
than arterial infarction
Determination of infarction
1. ischemic susceptibility (brain, kidney, heart)
2. anatomy of the vasculature (single vessel
ramifies, parallel system, dual blood supply –
LUNG)
3. overall cardiovascular function ( O2
concentration)
4. clinical significance of infarction
EMBOLISM
Embolus – solid abnormal mass transported from
one part of the body to another in the
circulatory system.
Embolism – process of travelling solid mass from
one part to another
 embolism is a common cause of
infarction
 important means of spreading disease
within the body
SHOCK – clinical term, peripheral circulatory
failure with pooling of the blood in the
terminal circulatory bed us small vessels
- result to insufficient blood is returned
to the heart, blood pressure falls and
flow is decreased.
- Result to redistribution of blood
Causes of shock
a. hypovolemic
b. cardiogenic
c. neurogenic
a.
hypovolemic shock – associated
with hemorrhage, trauma, loss of fluid
in burns and major surgery
b.
cardiogenic shock – failure of the
central pump
c.
septic shock – implies septicemia
or extreme localized infection, usually
with Gram negative bacteria /
organism, which is turn implies
endotoxemia
d.
neurogenic shock – usually result
from pain or severe emotional upset
 shock may be a major contributing
factor or perhaps the main cause of
death
Lesions indicative of shock
1. congestive atelectasis – shock lung
2. visceral pooling – no blood clots, lesion is
hemorrhage by diapedesis from dilated anoxic
capillaries in villi
3. acute renal tubular necrosis – renal
vasoconstriction result to fall in blood pressure,
lead to acute ischemic degeneration and necrosis
4. slugging – slowing down of the circulation,
settling out of red cells from plasma and
increased stickiness of blood
5. disseminated intravascular coagulation (DIC) –
widespread, or at times localized, formation of
microthrombi in capillaries, arterioles and
venules.
ACIDOSIS AND ALKYLOSIS
Blood pH: 7.35 to 7.45
Buffer system: bicarbonate, carbonic acid
Alkylosis – 7.8, extensive bicarbonate, less carbonic
acid
Acidosis – 7.0, excessive carbonic acid, less
bicarbonate
Metabolic acidosis – occurs in diarrhea as a result of
loss of sodium and bicarbonate from the
body
- in renal insufficiency as a result of
retention of acidic metabolites and ketosis
of diabetes or starvation
metabolic alkylosis – prolonged vomiting with loss
of fluids
respiratory acidosis – pneumonia (impaired
exchange of O2)
respiratory alkylosis – excess loss of CO2 during
rapid respiration
Dehydration – sunken eyes and loss of elasticity in
the skin
- leads to circulatory failure, hypovolemic
shock and renal failure
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EMBOLISM
Embolus – detached physical mass carried in the
blood stream from its site of origin to a
more distant site.
- most originate from thrombi
other sources:
1. fat
2. air bubble
3. tumor cells clumps
4. bacteria / parasites
5. amniotic fluid
6. bone embolism
 mostly intravascular emboli
 95% from thrombi in deep leg veins
Thromboembolism – from thrombi to embolus and
back to thrombi
FIBRINOLYSIS – (A) function to resolution of
thrombi, and (B) degradation of fibrin
deposited in inflammatory reaction and in
healing and repair process
- proteolytic degradation of fibrin clots,
mediated by PLASMIN
Fibrinolytic system – clot removal and enzymatic
degradation of fibrin
Zymogens – control fibrinolysis, an inactive
precursors
Plasmin – trypsin-like endopeptidase, hydrolyze
arginine and lysine bonds in fibrin and
fibrinogen
Plasminogen – inactive precursor of plasmin, found
in plasma, saliva, tears and milk
Serine proteases – activates plasminogen
THROMBI ORGANIZATION
Thrombi – dissolved by plasma-derived fibrinolysis
Organization – process undergone by thrombus not
dissolved by fibrinolysis
Recanalization – thrombus becomes vascularized to
restore blood flow, the surface is covered
with endothelium
EDEMA – accumulation of excessive amounts of
extracellular water in the interstitial fluid space
Interstitium – space between compartments binds
most cellular and structural elements into
discrete organ/tissue
Extracellular matrix / ECM – contains glycoprotein,
proteoglycans and glycosaminoglycan
* has insoluble fibrous and soluble gel
phase
basal lamina – separates ECM
fibronectine – connective tissue
laminin – basement membrane
collagens – ECM
Thixotrops – interstitial fluid gels
STARLING LAW
 net filtration pressure – arterial end
(7mm hg – hydrostatic pressure)
 net absorption pressure – venous end
(8mm hg – filtration/osmotic pressure)
Mechanism of edema
1. decrease plasma collagen / colloidal
osmotic pressure – decrease albumin
concentration
(hypoalbuminemia)
albumin – smallest protein
2. increase blood hydrostatic pressure –
hypertension / increase venous flow,
cardiac failure (CHF)
3. lymphatic obstruction – Elephantiasis
(Wuchereria bancrofti), localized edema,
failure to filter lymphatic fluid
4. increase vascular permeability – edema
of inflammation (change in endothelial
cells), high protein content
inflammatory edema ( exudates) – high specific
gravity, high cells and protein, tendency to
clot (fibrinogen)
non-inflammatory edema (transudate) – low sp.
gravity, cells and protein, less tendency to
clot (less fibrinogen)
Appearance of edema
1. dependent edema
2. pitting edema – produce dent(hollow) in tissue
3. renal edema
Anasarca – generalized edema
Ascites – peritoneal cavity
Hydrothorax – pleural cavity
Hydropericardium / pericardial effusion
12
Pulmonary edema – frothy exudate
Gall bladder and pancreas edema – glassy
Plasma protein
1. prothrombin
2. fibrinogen
3. albumin – most abundant
THROMBOSIS – solid mass within blood vessel
(thrombus/thrombi)
EMBOLISM – thrombus in blood stream (or any
foreign material)
Thrombus – pathologic blood clot formed
intravascularly
Blood clot – blood coagulation is physiologic
Chicken fat clot – necropsy in horses, plasma clot
due to rouleaux,
- intravascular but not pathologic
hemostasis – blood coagulation in extravascularly
(physiologic process)
 hemostasis and thrombosis involved
both blood coagulation
Pathologic coagulation
1. thrombosis – too much at the wrong time and
place
2. hemorrhage – too little when needed the most
Coagulation factors
1. fibrinogen
2. prothrombin
3. tissue thromboplastin
4. divalent calcium
5. proaccelerin
6.
7. proconvertin
8. antihemophiliac factor
9. Christmas factor
10. Stuart-Prower factor
11. Plasma Thromboplastin antecedent
12. Hageman factor
13. Fibrin stabilizing factor

Prekallikrein (Fletcher factor)

High molecular weight kinnegen (Fitzgerald
factor)
Intrinsic pathway – found in circulation
Extrinsic pathway – tissue factor
a. heparin
b.
heparan
sulfate
–
heparin-like
glycosaminoglycan
- found in endothelial surface
- catalyze the inactivation of thrombin by
antithrombin III
Pathogenesis of Thrombosis
1. changes in the vessel wall or surface
2. changes in hemodynamics of blood slow or
stasis
3. changes in blood itself and coagulability
role of endothelial cell (contain glycocalyx)
1. glycocalyx – has heparan sulfate (similar to
heparin, anticoagulant)
2. surface negativity – repels platelets and
leukocytes
Procoagulant endothelial
1. Thromboxane A2 – vasoconstrictor, platelet
aggregation
2. Von willebrand factor – platelets adhesion
3. Protacyclin – endothelial anticoagulant
Adhesion – stick to nonplatelets
Aggregation – stick to platelets
Platelet factor 3 – clot formation
Primary reversible aggregation – platelets undergo
shape change with pseudopod formation
Secondary irreversible aggregation – recruitment of
additional platelets and the release of
platelets granule protein
Thrombospondin – secreted by platelet a-granule,
binds to fibrinogen, stabilized platelet
aggregation
Morphology of thrombi
1. vascular thrombi – vascular system
2. arteriothrombosis – arteries
3. phlebothrombosis – vein
4. cardiac thrombosis – heart
5. valvular thrombosis – cardiac valves
6. mural thrombosis – wall of heart chambers
7. vegetation / vegetative valvular thrombosis –
cardiac valves
8. saddle thrombi – bifurcation between vessels
propagation – increase in thrombus
lines of Zahn – lamination of thrombi with platelets
and fibrin (white/pale thrombi)
13
red thrombi/stasis/ coagulation thrombi – red color,
gelatinous arterial thrombi
chicken fat clot – post mortem thrombi in horses
Fate of Thrombi
1. propagation – thrombi
producing obstruction
becomes
larger
2. embolism – fragmented
3. fibrinolysis (thrombolysis) – removed by
plasma-derived fibrinolytic system/phagocytosis
4. organized – in the vessel
14
CHAPTER 4: INFLAMMATION AND REPAIR
15
3.
Inflammation – vascular and cellular responses of
living tissue to injury.
- function to minimize the effect of an
irritant to the particular injured tissue
main response:
1. dilute 2. localize 3. destroy 4. removed the irritant
5. induced replacement
exudate – entered the tissue from the blood in an
active process.
- mixed with degenerative and necrotic
components of tissue, components of
the hemostatic system, products of the
immune
response
and
repair
mechanism
Phagocytosis – aids in removal and destruction
Histamine – released from mast cells, basophils and
platelets (A) dilation of arterioles, (B)
increase permeability
Anaphylotoxins – effectors of histamine release
Prostaglandin – stimulate histamine release
Kinins - plasma a-2-globulins “kininogen”- inactive
Kalikreins – activate kinins (kininases – activate
kilikreins) – NEUTROPHIL
Plasmin – liberates kinins and complement
(influence permeability)
Cellular response
1. Neutrophil – pseudopodia (also eosinophils)
2. Heterophils – birds, fish, reptiles
3. Monocytes quickly mature into macrophages
that are also histiocytes (muscle tissue)
macrophages – (from monocytes), similar to
tissue histiocytes
- phaocytosis, respond to chemotaxis, may
become epithelioid or giant cells
4. epithelioid / giant cells – similar to
macrophages, not required to phagocytize
- giant cells (fusion of cytoplasm of
macrophages)
Classification of exudates
1. Time – acute, subacute, chronic
2. Exudates (component)
a. serous exudate – clear fluid, mild injury
b. fibrinous – fibrin, severe acute vascular
injury
- ground-glass (early lesion)
- bread & butter characteristic
- fibrin cast (lumen filled with fibrin)
- diphtheritic membrane – causative
tissue filled with fibrin
c. hemorrhagic
exudate
–
hemorrhage/blood
- with fibrin and tissue debris
commonly misused term in
patholofy
d. catarrhal exudate – mucous membranes
(“to flow down”)
- acute and chronic lesion (one of the
most common exudate)
e. purulent exudate – pus as lesion
- suppurative – process of pus
formation
- mucous surface – mucupurulent
- serous surface - fibrinopurulent
f. granulomatous exudate – chronic,
lymphocytes and macrophages
Chemotaxis – process by which the attracting site
determines
the
migration
route
(chemotactic factor)
Neutrophil functions – (A) phagocytosis, (B) release
of lysosomes – lysis cells and tissue
A. GRANULOCYTIC SERIES – neutrophil,
eosinophil, basophils
1. Neutrophil – phagocytize / lyze debris
 phagolysosome – phagosome &
lysosome
 opsonic antibodies – antibodies help
phagocytosis
 regenerative shift – indicate more
neutrophils are made
 degenerative shift – marrow not
producing cells quickly
2. eosinophils – parasitic & allergic reaction
(common in acute arthus reaction)
3. basophils – least in granulocyes
B. MONONUCLEAR CELLS
1. Lymphocytes – smaller than macrophages (not
phagocytic) – B & T cells
2. Plasma cells – maturation and conversion from
B lymphocytes
- make and store antibodies
- indicate humoral immune response







three reaction
a. inflammatory – mononuclear
cells
b. reparative – connective tissue
c. degenerative - necrosis
granuloma
–
macrophages,
lymphocytes, and connective tissue
club colony / asteroid body –
eosinophilic blocks
cellulitis – acute purulent exudation in
subcutaneous tissues
pustule – pus in epidermis
abscess – pus in response to bacteria
pyogenic – bacteria causing pus
pyogenic membrane - wall
 healing of pus: absorption of the fluid
contents and removal and shrinkage of
the membrane
 pressure necrosis – assist the process of
rupture of abscess

Empyema –pus within body cavity
 Corynebacterium pyogenes - cattle
 Corynebacterium ovis - sheep
 Streptococcus sp. – horse/swine
MECHANISM OF TISSUE INJURY
1. TRAUMA – result to hemorrhage and necrosis
16
- wound or injury by physical or psychic
Wound – injury by physical means with disrupt of
normal continuity of structure
a. abrasion – denuded of skin or mucous
membrane
b. contusion – bruise/injury without
break in skin surface
c. laceration – tearing of tissue
d. incision – act of cutting open
e. concussion – violent jar shock
f. blast – wave / air pressure
2. IMMUNE INJURY
a. anamnestic response – re-exposure (faster
protection)
b. hypersensitivity – harmful effect of the
immune response
c. allergies – contact to exogenous
3. FEVER
Pyogens – substance alter body temperature
HYPERSENSITIVITY
1. TYPE I – Anaphylaxis
a. Cytotropic – Ab bound to tissue cells
(basophils/mast cells)
b. Aggregate – mediator release by Ag-Ab
complexes
c. Cytotoxic – Ab bind to Ag and cause
damage
2. TYPE II – Autoimmune disease result from
production of Ab to Ag
a. canine – autoimmune hemolytic anemia
b. chicken – autoimmune thyroiditis
c. rheumatoid arthritis – dog
d. canine systemic lupus erythmatosus
e. allergic encephalitis
3. TYPE III – Injury by Ag-Ab complex
a. Arthus reaction – accumulation of
neutrophils (immune complex disease)
4. TYPE IV – delayed hypersensitivity
a. Tuberculin reaction
(lymphokines – mediators secreted by
lymphocytes)
REPAIR – regeneration, to return to normal
anatomical and functional integrity of tissue
* repair, necrosis and inflammation occur
concurrently
First intention healing – proper apposition and
tissue are not lost
Second intention healing – tissue are lost, more
extensive
Granulation tissue and wound healing
 incision – present of hyperplasia of
fibroblast ( cut vessels undergo
hyperplasia & hypertrophy)
 Granulation tissue – new growth of
fibroblast and endothelial cells
- has collegenolytic properties
(clean debris and renew collagen)

macrophages – wound debridement and
promotes fibroblast proliferation

serum – has mitogenic factor ( stimulates
proliferation of fibroblast)

chalone – control fibroblast proliferation
(interfered by serum)

endothelial cells – secrets plasmin (lysis
fibrin)

myofibroblast – collagen with muscle fibril

internal restructuring – maturation of
collagen in healing wound

collagenase – breaking collagen
Healing in various types of Lesions
 fibrosis – harder\ning of tissue by
proliferation of connective tissue
 scirrhous – large amount of scar (Scar –
cicatrix)
 keloid – excess granulation tissue, large
amount of scar tissue
Therapeutic Influence
 corticosteroids – anti-inflammatory
 aspirin – inhibit prostaglandin
regeneration of tissue
- the most specialized the tissue, the
more limited to the capacity to
regenerate
- chalones – control tissue mass, inhibit
mitosis, negative feedback
17
INFLAMMATORY CONDITION
Peritonitis – peritoneum
Pleurisy – pleural cavity
Pericarditis – pericardium
Orchitis – testes
Myositis – muscle tissue
Meningitis – meninges
Mastitis – mammary gland
Laryngitis – larynx
Hepatitis – liver
Gingivitis – gums
Gastritis – stomach
Endocarditis – interior of heart
Encephalitis – brain
Bronchitis – bronchi
Blepharitis – eyelids
Ooporitis – ovaries
Salpingitis – fallopian tube
Pyelophlebitis – portain vein
Cholangitis – bile duct
Lymphangitis – lymph node
Cholecystitis – gall bladder
Cholelithiasis – gallstone
Arthritis – joint
Pancreatitis – pancreas
Tendonitis – tendon
Bursitis – bursa
Polymyositis – connective tissue & muscle
Pneumonia – lung
Angina – soft palate
Phlebitis – vein
Enteritis – small intestine
Enterocolitis – s.i. and colon
Dermatomyositis – conn.tisssue, muscle, skin
Sinusitis – sinuses (mucous membrane)
Pharyngitis –pharynx
Thyroiditis – thyroid
Dematitis – skin
Cystitis – urinary bladder
Conjunctivitis – conjunctiva
Cervicitis – cervix
Tonsillitis – tonsil
Spondylitis – spine (vertebrae)
Myelitis – spinal cord
Seminal vesiculitis – seminal vesiscle
Prostatitis – prostate gland
Balanitis – glan penis
Posthitis – prepuce
Ophthalmitis - eye
Keratoconjunctivitis – cornea & conjunctiva
Keratitis – cornea
Vulvovaginitis – vulva & vagina
Uveitis – uveal tract (eye)
Iritis – iris
Cyclitis – ciliary body
Iridiocyclitis – choroid
Eustachitis – eutachian tube
Rhinitis – nasal mucosa
Metritis – uterus
Stomatitis – mucous membrane
18
CHAPTER 5: DISTURBANCE OF GROWTH
* refers to excess growth, deficient growth or
abnormal patterns of growth
Factors:
1. number of cells in a tissue or an organ
2. size of the cells
3. combination of the number and size of the cells
4. change from the normal in the relationship of
cells or tissues to each other
term for lesions:
TROPH – nutrition
PLASIA – to form
Agenesis, Aplasia, Atresia
- reduced growth
- imply anomalous development
Agenesis – tissue or organ did not develop and is
absent
Aplasia – develop but the organ is markedly reduced
in size from normal
Aplastic – mean that there is no tendency to form
new tissue
- failure to regenerate
Atresia – absence or closure, of a normal opening
HYPOPLASIA
- incomplete growth
- range of incomplete growth occurs
- short of normal development
- did not reach its normal size or
structure
- decreased function and lack of normal
functional reserve.
ATROPHY
- decrease in the amount of tissue after
normal growth has been achieved and
as such is distinctive from hypoplasia.
- Cause by reduced number or size of
cells or combination.
denervation atrophy
- classic response of muscle to denervate
pressure atrophy
- pressure cause localized loss of cells
disuse atrophy
- keeping an organ in a cast
involution (complete atrophy)
- occurs in glands drained by ducts
allowing clean harvest of insulin from
the islets
Serous atrophy of fat
- lesion recognize during postmortem
examination
- indication of emaciation
- used of fat depots
HYPERTROPHY
- increase in tissue resulting from an
increase in the size of individual cells.
Compensatory hypertrophy
- occur because of loss of part of an
organ or in paired organs (kidney)
HYPERPLASIA
- increase in the number of cells in a
tissue or an organ
nodular hyperplasia
- hyperplasia that forms a localized area
within an organ result to a localized
nodule.
Cystic hyperplasia
- enlarging areas of retained secretion
resembles retention cyst
DYSPLASIA
- microscopic lesion in which there is a
loss of architectural orientation of cells
or a loss in uniformity of individual
cells or both.
- Abnormally developed tissue
-
-
dysplasia and hyperplasia may progress
to a truly neoplastic apprearance
carcinoma in situ
- intraepithelial tumor
- lesion has not broken through the
basement membrane
Euplasia - normal growth
Proplasia – slight increase or stimulation of growth
Retroplasia – decreased growth activity through
injury or aging
Anaplasia – cells and tissue that are poorly
differentiated and will be referred to again in
neoplasia
19
METAPLASIA
- transformation of a fully differentiated
normal adult tissue into a related type
of adult tissue
- common in mesenchymal tissues
- reversible
metaplastic bone
- island of bone tissue may form in
unexpected places
myeloid metaplasia
- spleen convert some space into bone
marrow
ANAPLASIA
TERATOLOGY
- study of anomalies
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Agenesis
Aplasia
Atresia
Hypoplasia
Developmental hypertrophy and hyperplasia
Failure of parts to coalesce/close
Persistence of vestigial structures
Supernumerary or accessory parts
Ectopic pr heterotopic parts (aberrant)
- organs located in abnormal places
Hamartoma
- improper mixture of tissue
Generalized anomalies of skeletal development
- chondrodystrophy/dwarfism
- arthrogryposis – born with flexed,
absolutely rigid limbs
Cellular and enzymatic malformations
Neoplasm
Veratrum californicum
- cause cyclepia in lamb
CLASSIFICATION OF ANOMALIES
Aplasia – absence of imperfect development
of an organ or part
- anlage is present
Acrania – absence of most or all of the bones of
the cranium
Anencephalia – absence of the brain
Hypocephalia – incomplete development of the
brain
Hemicrania – absence of half of the head
Exencephalia – defective skull with brain exposed
or extruded
hydrencephalocele – the protruding brain
contains a ventricle with filled with fluids
Arhinencephalia – absence or rudimentary
development of the olfactory lobe
Agnathia – absence of the lower jaw
Anophthalmia – absence of one or both eyes
Abrachia – absence of the forelimbs
Abrachiocephalia – absence of forelimbs and head
Adactylia – absence of digits
Atresia – absence of normal opening
Microphthalmia – incomplete development of the
eye resulting in an abnormally small organ of
vision
2. Fissures
Cranioschisis – skull
Cheiloschisis – lip (harelip)
Palatoschisis – oral cavity (cleft palate)
Rachischisis – spinal column
Schistorrachis / spina bifida – spinal column
Schistothorax – thorax/stemum
Schistozomus – abdomen
Schistocormus – thorax neck/ abdominal wall
3. Fusion of paired organ
Cyclopia – eyes
Ren arcuatus – kidney
- horseshoe kidney
DISTURBANCES IN DEVELOPMENT
B. EXCESS OF DEVELOPMENT
A. Arrest of development
1. Congenital hypertrophy
1. Agenesia – incomplete and imperfect
development of an organ or part
Hemihypertrophy – partial
20
2. Increase in number
Polyotia – ears
Polyodontia – teeth
Polymedia – limbs
Polyductyla – digits
Polymastia – mammary gland
Polythelia - teats
DISPLACEMENT DURING DEVELOPMENT
A. Displacement of Organs
Dextrocardia – transposition of the heart to
the right side
Ectopia cordis cervicalis – displacement of
the heart into the neck
B. Displacement of Tsissues
Teratoma – inclusion of multiple displaced
and also neoplastic tissue within an
individual
Dermoid – inclusion within an individual of
a mass containing skin (dermoid cyst)
Odontoid cyst – inclusion within an
individual of a mass of dental
enamel and cement (odontoma)
Dentigenous cyst – inclusion within an
individual of one or more
imperfectly formed teeth
Fusion of Sexual Characters
Hermaphrodite – a n individual having both
testicular and ovarian tissue
Pseudohermaphrodite – an individual having
unisexual development of the sex gland, but
having also either a unisexual or bisexual
development of the other parts of the
genitalia
Free martin – a female calf having arrested
development of the sex organs and being
the twin of a perfect male
Monster
(monstrosity) – disturbance of
development that involves several organs
and causes great distortion of the individual
CLASSIFICATION
1. separate twins
Acardius – malformed twin, while the other
is normal
Acephalus - lack of head
Amorphus – lack limbs
Acormus – lack trunk
2. united twins
Anterior Twinning
a. pygopagus – united in the pelvic region
with the bodies side by side
b. ischiopagus – united in the pelvic
region with the bodies at an obtuse
angle
c. dicephalus – two separate heads;
doubling may also affect the neck,
thorax & trunk
d. diprosopus – doubling in the cephalic
region without complete separation of
heads (only the face doubled)
Posterior Twinning
a. craniopagus – fused brain
b. cephalothoracopagus – union of head
& thorax
c. dipygus – doubling of posterior
extremities and posterior part of body
twinning almost complete
1. thoracopagus – united only by the thorax
2. prosopothoracopagus – besides the union of the
thorax and abdomen, the head & neck are
united
3. rachipagus – thoracic and lumbar portion of the
spinal column united
CYTOGENETICS
Polygenic inheritance – involves many physiological
characteristics of an individual
Diploid (2N) – somatic cells
Haploid (N) – germ cells
Heteroploidy – abnormal number of
chromosomes
Euploid / euploidy – an heteroploidy that is
exact multiple of haploid
Aneuploid – abnormalities do not involve
exact multiples
Trisomy – 3 chromosomes
Monosomy – 1 chromosomes
Mosaicism – nondisfunction result in an
abnormal number of chromosomes in
embryo
Gonadal dysgenesis – defects in the sex
chromosomes of human
21
Chimerism – 2 genotypes present in an
individual
Aging
a. cellular theory – cells functional genetic
program is the main influence and that it varies
with age
- due to “error in protein production”
(error catastrophe)
b. immune theory – immune functions decrease
with age, which in part accounts for
autoimmune disease and cancer in older
individuals
xxy – klinefelter’s syndrome (MALE)
xo – turner’s syndrome (FEMALE)
xxx- super female
free martin – twinning of cubs (Sta.
Gertrudis cattle)
CHAPTER 6: NEOPLASIA
Neoplasia – occurs when a group of cells becomes
free of normal growth control mechanism,
grows without regard for the normal
structural and functional aspects of tissue or
an organ and, in a manner of speaking,
becomes rebellious autonomous state.
Oncology – study of neoplasia
Cancer / tumor – common term of neoplasia
Boyd (1970) – the term neoplasia is restricted in
pathology to tumor growth, a process
which serves no useful purpose, which
continues unchecked and which is not
controlled by the laws of normal growth
although undoubtedly controlled in ways
that remain to be discovered.
Robbins (1976) – neoplasia is best considered as a
parasitic abnormal mass of cells which
grows more or less progressively unless
excised or controlled by therapeutic
intervention.
Willis (1967) – best accepted – a tumor is an
abnormal mass of tissue, the growth of
which exceeds and is uncoordinated with
that of the normal tissues and persists in the
same excessive manner after cessation of
the stimuli which evoked the change.
SUMMARY – NEOPLASIA is uncoordinated
proliferation of tissue, independent of the
structural and functional patterns of normal
tissue, and is indefinitely progressive.
CLASSIFICATION & NOMENCLATURE
Histogenesis – fundamental & primary
tumor must be named by the specific
tissue or cell type from which it arose
and of which it is composed
anaplastic / poorly differentiated tumor – tumor not
resembling its parent tissue
metaplasia/hyperplasia may be mistaken for
neoplasia
behavior – assessment of whether the tumor is
relatively harmless or a dangerous, lifethreatening lesion
 benign – tumor that are confined, slowgrowing and non-invasive
 malignant – invasive, rapidly growing
and dangerous
sarcoma – mesenchymal tissue
carcinoma – epithelial tissue
-
kinds of tumors
1. papillomas – skin (flat, smooth/villous –
WARTS)
2. adenomas – glands
3. basal cell – common group of epithelial tumors
in dogs
4. carcinomas – carry the name of tissue origin
5. lymphosarcoma – lymphocytes
6. leukemia – abnormal malignant cells present in
the circulating blood
STRUCTURE, APPEARANCE & GROWTH
gross description
1. location
2. color
3. size
4. consistency
5. appearance of the cut surface
22
Gross Features
- abnormal mass / greatly enlarge organ
(except lymphosarcoma)
- size is no indication of prognosis
- consistency (Firm – scirrhous tumor,
Soft – necrotic tumor)
Microscopic features
a. sheet of cells – monotomous pattern of masses
of cells with similar appearnce and very little
apparent stromal support; just cell after cell after
cell
example: lymphosarcoma, seminoma
b. acinar arrangement – chracterized by cells
forming or attempting to form acinar units, as in
a secretory gland like the thyroid / mammary
gland
c. nest of cells – typical of endocrine tumor, a
clump/nest of cells is surrounded by a narrow
band of connective tissue stroma
d. Palisading / trabecular pattern – occur when
cells line up in a picket fence type arrangement
along a strand of connective tissue. example:
testicular interstitial cell tumor
e. Tubular arrangement - occurs when single,
double or finger-like projections of tumor cells
invade surrounding tissue. Example: basal cell
tumor and gland tumor



scant – little apparent stroma (eg.
Sheets of cells)
locular – nest of cells
scrirrhous – dense stroma
growth of neoplasia




hemorrhage – testicular interstitial cell
tumor, may lead to thrombosis &
ischemic necrosis (hemangiosarcoma)
necrosis – prominent is many tumor,
pale and soft tissue
well differentiated tumor – tumor cells
that grows similar to parent tissue
poorly differentiated tumor – tumor
that resembles poorly to its parent
tissue
Anaplasia – marked lack of differentiation
Metaplasia –Mitotic index –relative numbers of
mitotic figures as indicative of rate of
growth
Doubling time – the time taken to double the size of
the tumor
 most cells produce in tumor die due to:
 pressure, ischemia, anoxia,
nutritive
competition,
abnormal mitosis
CYTOLOGY OF TUMORS
- the cells making up neoplasia are abnormal cells,
and the degree of abnormality usually
reflexes the degree of malignancy
- recognition of characteristics typical of neoplastic
cells is highly significant in diagnosing
tumor
cytopathology – determine whether a lesion is
neoplastic, inflammatory, degenarative or
hyperplastic
- the uniformity of normal cells is replaced
by
irregularity,
angularity
and
unpredictability in malignant cells
Characteristic of malignant cells
1. nuclear chromatin develops coarse clumped
patterns with sharp edges, sharp angles and
parachromatin clearing
2. nuclear membranes develops variations in
thickness, sharp, irregular, angled projection and
very well-defined inner and outer surface
3. nucleoli have irregular shapes with sharp
projections and indentations with marked
variation in size, shape and number
* multinucleation of cell is not a criterion of
malignancy unless the nuclei vary markedly in
size and shape
4. abnormal mitosis
5. abnormal karyotypes
6. cytoplasmic change
7. marked variability & irregularity of
neighboring cells
 no single feature is specific for
identification of a tumor cell
 neoplastic cells indicates that the
functions of the cells are directed
toward replication rather than carrying
23



out the normal physiological function
or work normally required of the
particular cells
the changes just mentioned are best
visualized in (A) dried smear, (B) wetfixed in alcohol in which shrinkage is
minimal
formalin fixed undergo shrinkage
poor fixation - autolysis
SPREAD OF TUMORS
1. infiltration
2. spreading via blood vessels
3. spreading via lymphatic vessels
4. implantation
 spread may be by direct expansion and
infiltration
 direct spread may be by
a. infiltration of tissue spaces
between cells
b. growth into the lymphatic
vessels
c. growth into the blood vessels
metastasis – implies spread to another area not
directly connected with original site
a. lymphatic vessels
b. blood vessels
2 theories of metastases
1. soil theory – tumor must find “suitable soil”
for its growth requirement before it will survive
as a metastatic nodule, thus perhaps accounting
for the favored sites of metastasis for some
tumors.
2. Mechanical theory – tumor will grow
wherever it lands, and only mechanical factors
and chance influence sites of metastases.
Implantation – usually peritoneum/pleura, in
abdomen results to ascites
Properties of cells for metastasis
1. decreased adhesiveness
2. loss of contact inhibition
3. increased mobility
4. increased contact guidance
5. synthesis of compounds that injure normal cells
three steps for metastasis of cells
1. release from the original site
2. transport and lodgment
3. survival & growth at the new site
Anticoagulant – reduce blood-borne metastasis by
blocking the formation of the thrombus
DIAGNOSIS & PROGNOSIS OF TUMORS
Diagnosis involves the tumor & the patient
1. species of animal and its breed
2. age, sex and location
3. clinical history (radiographic feature)
4. incidence & occurrence
5. characteristic locations
6. appearance
Tentative diagnosis
1. needle biopsy
2. exfoliative cytology
3. direct contact impression smears
histological grading – useful in evaluation of
prognosis
points to consider
a. differentiation
b. nuclear pleomorphism
c. hyperchromatism
d. mitoses
clinical grading – more significant in the survival of
the patient than histological grading for
canine mammary tumor
a. size
b. involvement of skin
c. involvement of underlying tissues to
arrive at a clinical grade
factor for prognosis
a. mode of growth / invasiveness – most
important factor for prognosis
b. histological grade
c. lymphatic premeation
d. location
e. treatment
f. regional lymph node
g. diameter & volume
h. delay in operation
Embryonic Antigen / Tumor markers
1. Alpha-fetal globulin – produced by
fetal hepatocytes
24
2. Carcinoembryonic antigen – antigens
are used for cancer detection, and are
produced by some tumor cells
Embryonic tumors
1. nephroblastoma
2. retinoblastoma
blastoma – poorly differentiated, have embryonic
appearance
eg. Spongioblastoma of nervous system
(not embryonic tumors)
teratomas – true tumors or neoplasms composed of
multiple tissues of different kinds, foreign
to the area in which they arise; tridermal
composition (ecto, endo, mesoderm)
hamartomas – structures that are abnormal mixture
or amounts of tissue indigenous to their
location
treatment of tumors
a. surgery
b. irradiation
c. chemotherapy
d. immunotherapy
* surgery and irradiation – only used for
animals
SURGERY – appropriate for small / localized
tumors
 treatment of any neoplasm is based on
early accurate diagnosis, careful
determination of the extent of the
neoplastic
process,
a
good
understanding of its biological behavior
and early adequate treatment.
 Irradiation and chemotherapy depends
upon killing cells and act particularly
during DNA synthesis & mitosis
 Therapeutic control of cell duplication
occurs through interruption of the cell
cycle. The rate of growth of a tumor
depends on the length of the cell cycle,
the number of cells active in growth
and the number of lost by death. The
cell cycle is often longer in a tumor
than in the normal tissue and cannot be
judge by the incidence of mitotic
figure.
IRRADIATION
a. quality of the irradiation source and its
energy
b. total dose and its time of delivery
c. associated sensitizing and protective
agents
d. characteristics of the tissue irradiated
* irradiation damage chromosomes and
affects the ability of the cell to
replicate
CHEMOTHERAPY – acts by interfering the
ability of the cell to divide
* the drugs bring about defects in mitosis or
in DNA & RNA synthesis and function, or
both.
* useful if used in young small tumor
IMMUNOTHERAPY – most recent, act against
the antigen of the tumor cell
2 METHODS
1. active immunization
a. specific active method – involves
immunization with either killed or
attenuated vaccines of tumor cells, but
many irradiated, or more commonly
chemically treated. Spontaneous
metastasis may be either facilitated or
suppressed.
b. Nonspecific active method – involves
the use of bacterial vaccines or
chemical compounds, or fraction of
them, that produce nonspecific
stimulation to the reticuloendothelial
system and that augment humoral &
cellular response to unrelated antigens.
c. Specific adoptive method – involve
injection of previously sensitized
lymphocytes.
2. Passive immunozation
a. specific passive methods – involved use
of immune system serum, but crossreactions and anaphylaxis may occur
with repeated dosage.
25
b. Nonspecific passive methods – use
humoral substances such as reagin or
properdin.




decreasing specific antibody levels tend to
indicate that metastasis will soon occur
most beneficial therapy will be a
combination
of
irradiation,
surgery,
immunotheraphy & chemotherapy
most forms of therapy result in
immunosuppression,
leukopenia,
and
thrombocytopenia, all of which lead to
complication
most patient with cancer become cachectic
– malignant cachexia
TRANSFORMATION – indicate that a heritable
change has occurred in cells
* in transformation, there is a change in one or all of
the characteristic of normal cells in culture
and the changes may occur simultaneously
or sequentially.
CARCINOGENS
1. irradiation
2. chemical
3. viral
trauma – co-carcinogen
IRRADIATION – influences oncogenesis by
mutation effects and results in errors or
genetic transcription.
CHEMICAL CARCINOGEN
a. polycyclic aromatic hydrocarbons
b. alkylating agents
c. azo dyes
d. aromatic amines
* act as promoters rather than initiators
promoters – (eg. Croton oil) act as growth
stimulants, proliferation of cells (essence of
promorion)
 a chemical carcinogen may induce
different kinds of tumors in organs,
depending upon the strain of animal,
the dose and route of administration
and the chemical used.
Theories of action
a.
deletion theory – a carcinogen causes the
deletion or inactivation of a key growth control
enzymes
b. direct damage to DNA or perhaps RNA, which
result in transcription into DNA
c. activation of latent oncogenic viruses
d. assistance with the selection of clones of
initiated cells
VIRAL ONCOGENESIS
Transplantable – can be pass with whole cell
Transmissible – passes with cell0free passage
Key factors in the progress of viral oncogenesis
1. recognition of the carrier state of the viruses and
that other factors may influence the expression
of a tumor caused by a virus
2. recognition of the importance of the strain of
animal in terms of susceptibility, thus the
genetic influence in so-called high or low
incidence strain
3. recognition of age susceptibility as a factor, of
which little is known until newborn animals
were used in testing programs.
DNA VIRUSES – papova group
1. permissive cells of a natural host – occur of
productive infection
2. nonpermissive cells of an unnatural host –
induced permanent heritable change by
transformation
 the cell is not lysed, but the viral
genome, is replicated with it and may
later influence certain properties of the
host cell in such a way as to induce
transformation
 adenovirus are not known to cause a
natural tumor
 marek’s
disease
(temperaturedependent oncogenic herpesvirus)
RNA VIRUSES
Leukoviruses / oncornaviruses – RNA virus causing
leukemia / lymphosarcoma
- consistent physical, chemical & oncogenic
properties
lymphosarcoma – from both T & B cells
reverse
transcriptase –RNA-dependent DNA
polymerase
- enzyme found in RNA viruses
26
- enzyme used by viral RNA genome to
make a DNA copy of itself called
PROVIRUS
provirus – serves as a template for virus production
and is inserted into the genome of the cell
DNA virus – the cell is transformed and new virus
is produced (not in RNA virus)
the normal gene pool of all vertebrates and is
passed vertically by the unusual mechanism of
inheritance.
* these oncogene is normally repressed but
may depressed by carcinogens, irradiation
or aging
2. protovirus –based on the potential for genetic
evolution in cells
Theories for RNA virus oncogenesis
1. oncogene theory –portion of the oncornavirus
genome existing as the DNA provirus is part of
- prosed that transfer of information from DNA to
RNA to DNA occurs in somatic cell result to alteration
of genes
CHAPTER 7: HOST-PARASITE
RELATIONSHIP
Henle-koch postulate
1. the parasite occurs in every case of the
disease in question and under
circumstances which can account for
the pathological changes and clinical
course of the disease
2. it occurs in no other disease as a
fortuitous or nonpathologic parasite
3. after being fully isolated from the body
and repeatedly grown in pure culture, it
can induce the disease anew.
Factors influential in infectious disease
Symbiosis – living together; microorganisms and
parasites may coexist with a host by living
in or on the host
a.
mutualism – 2 live together without
disadvantage to either; lower animals
b. commensalism – advantage to one partner but
no real disadvantage to the other
c. parasitism – one partner damages the other
during their coexistence and induces disease in
the member generally considered to be host.
THE HOST
Resistance – host primarily protective factor
a.
genetic resistance – natural resistance
the agent may enter the host but not
become established or even if it does
become established, causes no ill
effects.
- Eg: Pneumostrongylus tenuis – larvae;
neural tissue of white-tailed deer
b. Age resistance – particular agent may infect a
young animal and cause lesions but be harmless
or less harmful in an older animal of the same
species, and the reverse may occur.
c. Immune resistance – acquired through previous
natural exposure to an agent or through
immunization but may be partly natural.
d. Nutritional resistance – an animal in good
nutritional condition is more resistant to disease
than one in poor condition.
-
THE AGENT
1. virulence – implies the ability to invade and
cause lesions, with greater degrees of virulence
being associated with more serious
consequences for the host.
2. Tropism – factor in favor of the agent and may
allow it to strike at a vital site, as in a case of
rabies. EG: placenta has erythritol (favored
brucellosis)
3. Persistence – ability to survive to cause disease;
may often be accomplished best maintaining an
intracellular existence, except for periodic
disruptive excursions outside.
Response to virulence
a.
clinical disease – as a result of infection results
from abnormal functional and morphological
27
changes in constituents of the body that upset
homeostasis and cause illness.
b. Subclinical disease – depend on the extent to
which the animals are observed, how detailed
the clinical examination is or the number and
type of laboratory tests carried out. (the animal
do not show obvious signs of clinical illness, but
production is reduced).
c. Latent infection – state beyond the subclinical
state. Inapparent carrier. Individual harbors and
excretes a known pathogen but has no clinical
evidence of the disease. EG: Salmonellosis &
Herpes virus.
- subclinical or latent infection may cause
clinical disease after variations in
environmental conditions or immune
status of the host
THE ENVIRONMENT
 the factors that are of greatest
importance in initiating or influencing
disease.
 May change the subclinical or latent
infection into acute or chronic disease
Eg: Ammonia (mycoplasma sp)
Weaning, shipping & crowding
(normal flora)
PATHOGENESIS OF DISEASE CAUSED BY
VARIOUS AGENTS
I. BACTERIA
a. acute bacterial disease – rapid
accumulation of organisms that have
gained entry
EG:
pateurella hemolytica – sheep
Actinobacillosis equuli –
horse
Clostridium tetani – needs
less amount of bacteria to cause
disease
b. chronic bacterial disease – agent persist
in the host for a long period
requirement for pathogenicity
a. enter the host by surviving on and penetrating
mucous membrane
b. multiply in vivo
c. inhibit or avoid stimulation of the host’s defense
mechanisms
d. damage the host
virulence – degree of pathogenecity
Aggressins – general name for the compound
release by bacteria to break down the host’s
defense mechanism
Ways for producing disease
a. attaching to an epithelial surface and secreting
toxins (enterotoxigenic E. coli)
b. invading the epithelial cells and destroying them
(Shigella)
c. invading the lamina propria in order to
disseminate from there (Salmonella)
iron – may contribute to rapid increase in growth of
organisms in experimental tissues
II. VIRUSES
Caused disease by:
a. cytolysis
b. maintaining a steady state with
the host
c. integrating into the genome of
the host
cytolytic effects – arise from destruction of the host
cell following maturation of the virus
intracellularly and the release of the new
infectious virus into the environment.
* The steady state type of infections are typically for
RNA viral infections
Integrated infections – characteristic of the
oncogenic viruses (slow virus infection)
Cytopathic change – altering the form and function
of membranes and organelles either
selectively or nonspecifically
* persistent infection may lead to immune-complex
disease
III. PARASITES
* parasitic agents generally cause disease by local
destruction of cells or tissue, by their effects
on the blood circulation, by their effects as
space-occupying lesions or by nutritive
competition.
a. immune-complex
disease
(malaria,
trypanosomiasis, schistosomiasis)
* cell-mediated immunity – major factor in the
development of parasitic granuloma
b. blood-lost – hookworm infection (haemonchus)
IV. FUNGAL
1. invasion – of living
28
2. allergies – resulting from contact with an
development of hypersensitivity to fungal
antigens
3. toxicosis – eating food containing toxic
metabolites of fungi
farmer’s lung – man & cattle (Micropolyspora faeni)
Aflatoxins – Aspergillus flavus, A. parasiticus
Moldy corn poisoning – Fusarium spp
Photosensitization syndrome – Sporidesmium bakeri
Ergotism result to gangrene of extremities –
Claviceps purpurea
CHAPTER 9: IMMUNOPATHOLOGY
Pre-pre B cells – rearrangement of heavy chain
genes
Pre B cells
- cytoplasmic heavy chains
Immature B cells – surface IgM
Mature B cells - surface IgM & IgG
Plasma cells
Null cells – are lymphocytes that are not definable
by T cells & B cells
- can be natural killer cells or killer cells
- does not need previous sensitization
Antigen-presenting cells
a. macrophages
b. langerhan cells
c. dendritic cells
Reaction
TYPE I
TYPE II
TYPE III
TYPE IV
Immunologic
mediator
IgE
IgG, IgM
IgG, IgM
Sensitized cells
IMMUNOGLOBULINS
 IgA – large molecules (pentamere),
secreted during early/primary immune
response
 Ca not cross placenta
1. IgM – cannot cross placenta, activate
COMPLEMENT
2. IgG – most abundant in serum, secreted during
2nd antigen response
- can cross placenta; can be found in
colostrum
- activate complement and act as
opsonin
3. IgA – found in glands (tears, Saliva) and GIT,
activate alternate complement pathway
4. IgE – allergy, Asthma, parasitic; surface in
basophil & mast cells, but not in Eosinophils
5. IgD – receptor for B cells
Mechanism
Mediator response
Cytotoxic
Immune complexes
Delayed-type hypersn.
Disease sample
Anaphylaxis, asthma
Autoimmune hemolytic anemia
Glomerulonephritis
Tuberculosis
29
TYPE I – first and second exposure
Th2 – T-helper 2 (secrete interleukin 4 & 5)
IL 4 – stimulate B-cell growth
IL 5 – stimulate & activate eosinophil &
differentiation of B-cells
- increase production of IgA
basophil and Mast cells – found in skin surface
Mediator of type I
a. histamine – vasodilation, increase
permeability of vessels, contraction of
bronchial smooth muscle
b. arichidonic acid
c. platelet activating factor
d. IL 4 & 5
e. Tumor necrosis factor
Localized reaction/ disease
a. conjunctivitis
b. asthma
c. allergies
d. angioedema
e. urticaria & allergic reaction
systemic reaction
a. anaphylaxis
clinical signs
a. vomiting
b. crumps
c. pruritus
d. diarrhea
e. dyspnea
TYPE II – antibody dependent cytotoxicity
Diseases
a.
autoimmune hemolytic anemia – RBC
are antigen
b. Erythroblastosis fetalis – maternal
antibody destroy fetal RBC
c. Phemphigus vulgaris
d. Good Pasture disease – hemoptysis &
hematuria
e. GRAVE
disease
–
man;
hyperthyroidism & exolphthalmus
f. Miasthemia
g. Perncious anemia
Type III
– deposition of immune complexes
activates complement causing inflammation
Local reaction
a. arthus reaction
Systemic reaction
a. serum sickness
clinical example
a. serum sickness – drug
b. heroin – glomerulonephritis
c. quinidine – antimalaria, hemolytic
anemia
d. post-streptococcal glomerulonephritis
e. farmer’s lump mycosis (fungi)
endogenous antigen
a. systemic lupus erythromatosis – nuclei
antigen
b. rheumatoid arthritis – Ig are involved
TYPE IV
Alpha interferon – activates macrophages and
formation of epitheloid (granulomas)
Alpha tumor necrosis factor
Cytotoxic T-lymphocytes
Clinical example
1. delayed type hypersensitivity reaction
a. contact dermatitis
b. poison ivy & poison oak
c. mantoux test – specific test
for tuberculin
d. van der bergh’s test – specific
test for bilirubin
2. cell mediated
a. transplant rejection
autograft – self to self
isograft – identical twins
allograft – person to person; variable acceptance
xenograft – heterologous; between species
type of rejection
a. hyper-acute rejection – occur right after
the transplant
b. acute rejection
c. chronic rejection
* graft versus host disease – bone transplant