general pathology laboratory 2010-2011

7/28/2019 General Pathology Laboratory 2010-2011

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CONTENT

GENERAL PATHOLOGY......................................................................................................1

DEFINITIONS........................................................................................................................2

DISORDERS OF LIPID METABOLISM..............................................................................3

Hepatic LIPIDOSIS (liver STEATOSIS, fatty liver))............................................................3Kidney STEATOSIS (in equine hyperlipemia)......................................................................5

DYSTROPHIES OF PROTEIC METABOLISM.................................................................6

Amyloid dystrophy (AMYLOIDOSIS, hepatic amyloidosis)................................................6

Kidney HYALINOSIS............................................................................................................7

DISORDERS OF HIDROELECTROLITIC METABOLISM............................................8

Kidney GRANULO-VACUOLAR DEGENERATION.........................................................8

DISORDERS OF MINERAL AND PIGMENTARY METABOLISM...............................8

Jaundice...................................................................................................................................8

Renal mineralization (Dystrophic calcification of kidney)...................................................10

PATHOLOGY OF CIRCULATORY CHANGES PART I.............................................11

Pulmonary congestion (hyperemia) and edema ...................................................................12Muscle hemorrhage...............................................................................................................13

White kidney infarct..............................................................................................................13

PATHOLOGY OF CIRCULATORY CHANGES PART II...........................................14

Hepatic venous THROMBUS...............................................................................................14

Acute and passive liver congestion.......................................................................................16

INFLAMMATION.................................................................................................................17

ALTERATIVE INFLAMMATIONS....................................................................................19

Necrotic hepatitis (diffused and miliar)................................................................................19

Chronic gastric ulcer (Chronic ulcerative gastritis)..............................................................20

EXUDATIVE INFLAMMATIONS......................................................................................21Fibrinous pneumonia (Lobar pneumonia).............................................................................21

Purulent (suppurative) leptomeningitis.................................................................................22

Pulmonary abscess................................................................................................................24

PROLIFERATIVE INFLAMMATIONS.............................................................................25

Echinococcus Hydatid Cyst..................................................................................................25

Actinobacillosis.....................................................................................................................27

Tuberculosis..........................................................................................................................28

REPARATORY PROCESSES (REGENERATION AND REPAIR) ..............................32

Granulation tissue (Young connective tissue).......................................................................34

Bone regeneration Bone callus...........................................................................................37

TUMORS PATHOLOGY......................................................................................................38EPITHELIAL TUMORS.......................................................................................................40

Squamous cell carcinoma (SCC)..........................................................................................40

Trichoblastoma - Ribbon Type.............................................................................................41

Papillary carcinoma of the mammary gland.........................................................................41

MESENCHYMAL TISSUE TUMORS................................................................................44

Poorly melanotic MELANOMA............................................................................................44

Osteoblastic productive OSTEOSARCOMA ......................................................................45

Cavernous HEMANGIOMA................................................................................................47

FIBROSARCOMA...............................................................................................................48

GENERAL PATHOLOGYGENERAL PATHOLOGY

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DEFINITIONSDEFINITIONS

Morfopatology. Morphe- shape,pathos- disease, logos-science.

Anatomical pathology

Ana (gr.)- throughToma (gr.)- cut

- The study of disease (lesions but also cause)

- Connects the study of normal form and function (histology, anatomy,

physiology) to the study of clinical medicine

-Makes sense how the various causes of disease interact with the host, resulting

in clinically identifiable conditions

The medical science and specialty practice, concerned with all aspects of disease,

but with special reference to the essential nature, causes and development of abnormal

conditions, as well as the structural and functional changes that result from the disease

processes (Stedmans Medical Dictionary).

The main methods of study (instruments) of anatomical pathology:

1. Necropsy: (necros-death, opsis-sight): opening and examination of the dead

bodies for the establishment of the exact (nosologic) diagnose (nosos-disease, logos-

science).

2. Histopatholoy and citopathology: continuation of the macroscopic studies in

the laboratory with the help of the microscope.

3. Biopsy: tissue removed from lived animals, from organs with changes, to

provide diagnose to help clinicians.

4.Experimental reproduction

Pathology:

-General pathology:

-basic responses of cells and tissues to insults and injuries, irespective of the

organs, systems or species involved

Metabolism changes

Blood and lymph changes

Morphofunctional adaptation processes;

Inflammations

Regenerative processes

Tumoral process

-Special pathology (pathology of organ system, systemic pathology):

-how each organ system reacts to injury associated with specific disease

General plan of examination for organs and tissues

1. Inspection

- development of organs (estrogenic micotoxicose)

- color (carotenoids, bile pigments, blood circulation, fibrosis)

- shape and dimensions

- aspect of surface and margins

2. Palpation (consistency changes)- superficial

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- profound (bony, flashy, hard, pasty, puffy, elastic, friable)

- increased: coagulation necrosis, proliferative inflamations, mineralization,

tumors with much connective tissue, compression atrophies

- decreased: liquefaction necrosis, gangrenes, exsudative inflammations,

autolysis, putrefaction, highly celularised tumors

3. Sectioning- standard (lung, liver, spleen, gut, stomach, kidney, brain)

- whenever necessary

4. Collection of samples for laboratory exams

- histopathology

- hematology

- cytology

- bacteriology

- parasitological

- virusology

- mycology

- toxicological5. Special exams

- docimasy

- choledoch exam

DISORDERS OF LIPID METABOLISMDISORDERS OF LIPID METABOLISM

- Cholesterol (ateromathosis)

- Complex lipids (cerebrosidosis)

- Triglycerides (obesity, steatosis, lipomatosis, cahexia)

Hepatic LIPIDOSIS (liver STEATOSIS, fatty liver))Hepatic LIPIDOSIS (liver STEATOSIS, fatty liver))

Definition: Hepatic lipidosis is the term most often used to describe fatty livers of

animals, whereas in humans, the term steatosis is more commonly used. Both refer to the

visible accumulation of triglycerides (triacylglycerols) as round globules in the cytoplasm of

hepatocytes. The threshold for application of these terms is vague because triglyceride storage

and transport are normal hepatic functions, but they are appropriate when the amounts are

greater than would normally be seen.

Etyology:Hepatic lipidosis can bephysiologicalorpathological.

Increased mobilization of triglycerides during late pregnancy or heavy lactation in

ruminants is associated with hepatic lipidosis. In some of these animals, severe energy

deficiency can also lead to clinical ketosis with metabolic acidosis. In addition, severe

lipidosis occurs in high-producing dairy cows fed diets where either the mix of available fatty

acids is incorrect or lipids are oxidized and rancid.

Hepatic lipidosis is common in injured hepatocytes. Physiologic fatty liver occurs in

late pregnancy and heavy lactation, particularly in ruminants. Lipidosis is also seen in

neonates, especially in those species whose milk is relatively rich in fat.

Acute ketosis of lactating dairy cows with intake insufficiency or secondary to

abomasal displacement is usually associated with fatty liver with a predominantly diffuse

microvesicular pattern. Cows are more tolerant of ketosis associated with lactation than are

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pregnant ewes that can die from starvation-induced pregnancy toxemia and ketoacidosis. In

cows and ewes with increased mobilization oftriglycerides, there may be indistinct foci of

white discoloration of abdominal fat that tend to be obscured when adipose tissue solidifies

postmortem.

Fatty liver of diabetes occurs when insulin is deficient or inactive due to lack of

functioning receptors.Lipoprotein synthesis and transport are dependent on oxidative metabolism, so hypoxia

of hepatocytes leads to triglyceride accumulation. The two most common causes of

hepatocellular hypoxia are anemia and reduced sinusoidal perfusion in passive venous

congestion.

Local hypoxia is probably the basis for another example of fatty liver in bovine so-

called "tension lipidosis".

Fatty liver due to intoxication is common. Most toxins that cause fatty liver in naturally

occurring situations, however, also produce a greater or lesser degree of hepatocellular

necrosis.

Tthere are some specific nutritional deficiencies that will produce fatty liver. Choline

deficiency, in conjunction with deficiency of other lipotropic factors such asL-methionine andvitamin B12, rapidly produces fatty liver.

Hepatic lipidosis is common in companion animals. Dogs eating diets deficient in

vitamin Emay develop severe hepatic lipidosis.

The syndrome offeline hepatic lipidosis most commonly occurs in obese, nutritionally

stressed female cats, presented with vomiting, anorexia, weakness and weight loss, jaundice,

and hepatomegaly.

Familial hyperlipoproteinemia has been described in cats, associated with congenital

lipoprotein lipase deficiency.

The microscopic appearance of triglyceride globules in hepatocytes ranges from small

discrete microvesicles (acute) to large coalescing macrovesicles (chronic).

o Small droplets of fat, usually in a periportal and juxtasinusoidal position, can

normally be found in the liver. Increased mobilization and acute injury tend to

produce microvesicular lipidosis in which numerous small and discrete micellar

lipid globules are distributed around the central nucleus. Acute lipidosis with

predominantly microvesicular accumulation tends to result grossly in a modestly

enlarged pale liver without much change in texture.

o In some more protracted toxic injuries, lipid globules tend to coalesce into large

central macrovesicles that displace the nucleus (signet ring cell). Grossly,

these fatty livers tend to be more yellow, enlarged, and the texture is more

friable. Each hepatocyte usually contains one large globule (macrovesicle) thatalters the contour of the cell and displaces the nucleus. The sinusoids are

compressed and appear underperfused, and the tissue at low magnification

resembles adipose tissue.

The triglyceride globules themselves are not harmful to hepatocytes, so the amount of

fat present is more an indicator of the duration of insult and triglyceride supply than of the

severity of hepatic injury.

Evolution:In severe degeneration, the liver is moderately or greatly enlarged, with a

uniform light yellow color. The edges are rounded, and the surface is smooth. The cut surface

has a diffuse greasy appearance, or a red and yellow lobular pattern if there is also hepatic

congestion or zonal necrosis. The parenchyma is less dense and portions will float in water or

fixative.

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When lipid accumulates in large amounts, there is a tendency for groups of the fat-laden

cells to rupture or fuse and eventually form a multinucleate rim about a foamy mass of lipid.

This epithelial structure is known as a fatty cyst, as is the next stage, which occurs when

released lipid is picked up by macrophages.

Lipidosis is usually reversible, although a liver that has been fatty for some time is

more likely to have concurrent damage, including fibrosis, pigment accumulation, andnodular hyperplasia.

Kidney STEATOSIS (in equine hyperlipemia)Kidney STEATOSIS (in equine hyperlipemia)

Definition: kidney dystrophy due to TG accumulation in the nephrocytes.

Etiology:

- hyperlipemia in horses,

- intoxications with Liliaceae in cats,

- nutrition rich in lipids,

- hipotyroidism,

- chronic nephritis,

- steroid hormones treatment.

Equine hyperlipemia is almost exclusively a disease of ponies, and among these the

Shetland breed predominates. The disease has also been reported in American miniature

horses and donkeys. The disease is usually fatal after about a week.

Pregnant or lactating mares are most likely to develop the disease, particularly if they

are excessively fat and have recently suffered reduced feed intake due to onset of parturition,

conditions such as laminitis orparasitism, or other causes ofstress.

At necropsy liver is severely fatty and may have ruptured; the lipidosis also extends to

heart andskeletal muscle, kidney, and adrenal cortex. Evidence of disseminated intravascularcoagulation is seen as serosal hemorrhages and microscopic thrombi in various organs, and

even gross infarction of myocardium and kidney.

The pathogenesis of this disease is obscure:

1. Since the excess lipid in liver and blood is in the form of triglyceride,

the implication is that the liver is capable of esterifying fatty acid mobilized from

depot fat. The triglyceride thus formed is presumably then exported to the plasma as

VLDL until the plasma transport mechanisms are saturated, at which stage lipids

begin to accumulate in the hepatocytes.

2. Another possibility is that there is an inability on the part of all tissues

other than the liver to utilize fatty acids from VLDL at the normal rate, while

triglyceride synthesis from fatty acids continues in the liver.3. It has been proposed that an underlying cause of pony hyperlipemia is a

comparative resistance to insulin in susceptible animals.

Gross lesions: Friable kidneys, of yellowish color, greasy aspect on section, mainly in

the cortical area.

Microscopically findings:

Foamy aspect of nephrocytes due to lipid accumulation (vacuoles)

Increase in size of nephrocytes with reduced lumen of tubules

Sometimes pyknotic nuclei (pushed to a side) - signed ring cell aspect

Fatty cylinders are formed (fusion of affected cells)

Evolution: renal insuficiency; renal failure.

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DYSTROPHIES OF PROTEIC METABOLISMDYSTROPHIES OF PROTEIC METABOLISM

Proteic dystrophies

- Amyloidosis

- Hialynosis and hyalinisation

- Fibrinoid degeneration most frequently affecting arteries- Mucoid degeneration affecting mucus-secreting epithelium

- Coloid degeneration (hipothyroidism) affecting thyroid follicles

- Dyskeratosis - Premature keratinization in cells that are not in the keratinizing

surface layer of the skin

Hyaline substances:

1. Hyaline casts in the lumen of renal tubes (proteinuria).

2. Serum or plasma in blood vessels.

3. Plasma proteins in vessel wall (edema disease - swine).

4. Old scars.

5. Thickened basement membranes (glomerulonephritis and capillaries of choroid plexus

aged animals).

6. Hyaline membranes of alveolar walls.

7. Hyaline microthrombi in DIC (disseminated intravascular coagulation).

8. Amyloid.

Amyloid dystrophy (AMYLOIDOSIS, hepatic amyloidosis)Amyloid dystrophy (AMYLOIDOSIS, hepatic amyloidosis)

Definition: Amyloidosis is a systemic disease in which the eosinophilic, homogenous

material is deposited extracellular in multiple regions, particularly in the renal glomerulus.

On hematoxylin and eosin staining, amyloid appears as homogeneous eosinophilicamorphous extracellular material. Staining with Congo red results in apple green

birefringence when viewed with polarized light. Thioflavine T stain produces yellow-green

fluorescent staining of amyloid viewed under ultraviolet light.

Amyloidosis affects parenchymatous organs, especially the kidneys, liver and spleen.

- At the hepatic level, amyloid is depositedfirst in the parenchyma about the portal

tracts and appears gray and waxy. Amyloid is deposited in the perisinusoidal

space between the sinusoidal lining and hepatocytes and is sometimes found in the

walls of the afferent vessels. The surrounded hepatocellularcords atrophy.

- In kidneys , amyloidosis is seen in the vascular glomerular ball form.

- In the spleen, amyloidosis occurs around the lymphoid follicular arterioles.

- Due to the predominant extracellular location of the amyloid (exceptions are BSE-Bovine Spongiform Encephalopathy where the amyloid is deposited

intracellularly, in the affected neurons), amyloidosis is not a proper dystrophy

since the hepatic dysfunction is produced after the compressive effect the amyloid

plays on the hepatocytes.

Etiology - Amyloidosis is seen in diseases with chronic, long lasting evolution as

tuberculosis, leukosis, mink plasmocitosis, classical swine fever, chronic suppurative

diseases, neoplasia and even in BSE. In cattle, amyloidosis is secondary to the chronic process

of tissue distruction; in some cases it is associated with chronic suppurative and

granulomatous lesions in other tissues. Horses used for the production of hyperimmune serum

could also be affected by amyloidosis.

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In horses, hepatic amyloidosis occurs chiefly as a result of chronic inflammation and

has been well recognized in horses used for the production of hyperimmune serum. Horses

may develop icterus and other signs of hepatic failure.

Cattle die first of the primary disease or from uremia resulting from concurrent renal

amyloidosis.

Dogs and cats typically develop signs of renal dysfunction, although cats may bepresented with spontaneous hepatic rupture. Familial AA amyloidosis is recognized in

Chinese Shar-Pei dogs, in Abyssinian cats, and suspected in Siamese and Oriental cats.

Depending on the mechanism of production, we can see:

- Primary Amyloidosis (AL - amyloid light chain) occurs in plasma cell diseases

and of B lymphocytes that have the capacity to form immunoglobulins

following prolonged antigenic stimulation. It occurs in immune diseases and

tumors eg. Multiple myeloma.

- Secondary Amyloidosis or Reactive Amyloidosis (SAA - serum amyloid-

associated) occurs when serum proteins are produced in excess by either

hepatocytes or other cells, or following tissue destruction consecutive to a

chronic disease.Gross lesions - The liver is: slightly enlarged in volume, with a pale gray-yellowish

color reflection, friable, dense, and waxy to the touch, dry on cross-section and prone to

fracture. Hepatic amyloidosis gives the organ the aspect of a wax block. In cattle, affected

livers may be firm.

Microscopically - at the level of the liver, the lesion starts inside the Space of Disse

(between the Remak chords and the endothelial sinusoidal capillaries perisinusoidal space)

which thus becomes obvious at this level due to the unstructured, homogeneous deposits that

induces the narrowing of the sinusoid capillaries and the atrophy of the Remak chords.

Hepatocytes appear atrophied, edgy, differ in shape and size, many of them undergoing

necrosis (different stages) with barely distinguishable nuclei. Sinusoid capilaries ar also

atrophied with histoarhitectural changes of liver.

EvolutionEvolution - The lesion is irreversible, leading to a chronic hepatic insufficiency and

cirhosis. Affected livers are predisposed to rupture and bleed.

Kidney HYALINOSISKidney HYALINOSIS

Definition: kidney dystrophy due to hyalin (homogenous granular protein aggregates)

intracellular and extracellular accumulation (hyalinosation) in the nephrocytes of the

epithelium tubes.

Etiology:Hyalinosis (intracellular)

-nephrocytes (cronic kidney disease, with massive

proteine resorbtion albumin, myoglobin, hemoglobin

-hepatocytes (chronic toxicity, viral diseases, chronic

alcoholism in humans)

-plasma cells (Russel body chronic diseases)

Hyalinisation (extracellular)

-vascular and epithelial (virosis)

-muscle distrophy and necrosis

-devitalized tissues (thrombosis,

granulomas, scars)

Gross lesions: kidney enlargement, dry on section, pale aspect, (glassy aspect)


- cell hipertrophy due to intracitoplasmatic accumulation of multiple granularoxifile Hyaline bodies (first stage)

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- cell membrane lysis, liberation of the bodies in the lumen and formation of

Hyaline cylinders (second stage).

DISORDERS OF HIDROELECTROLITIC METABOLISMDISORDERS OF HIDROELECTROLITIC METABOLISM

- Cell edema

- Granular dystrophy

- Vacuolar dystrophy

- Hidropic degeneration (Balonisation)

Kidney GRANULO-VACUOLAR DEGENERATIONKidney GRANULO-VACUOLAR DEGENERATION

Definition: kidney dystrophy due to excessive cell hidratation (disorders of Na-K ionic

pumps) in the nephrocytes of the epithelium tubes.Other organs affected: liver, suprarenal glands, neurons, muscle a.o.

Etiology: different toxically agents (As, P), tissue hypoxia (predominant cause),

hipopatasemia, febrile syndrome, infectious diseases (Leptospirosis).

Gross lesions: kidney enlargement, increased consistency, pale aspect, (boiled organ

aspect).

Microscopicallyfindings:

Granular dystrophy

- nephrocytes enlarged

-granular, dirty aspect of cytoplasm dueto mitochondrial hypertrophy (water

accumulation)

Vacuolar dystrophy

-enlarged nephrocytes

-vacuolar aspect of the cytoplasm due to cellhiperhydratation (oedema of REN, mitochondria,

cytosol) foamy aspect

Evolution

Granular dystrophy

1. Reversible

2. Vacuolar dystrophy

Vacuolar dystrophy

Initially reversible, then cell necrosis

DISORDERS OF MINERAL AND PIGMENTARY METABOLISMDISORDERS OF MINERAL AND PIGMENTARY METABOLISM

JaundiceJaundice

Definition: also known as icterus is a yellowish discoloration of the skin, the

conjunctive membranes over the sclera and other mucous membranes caused by

hyperbilirubinemia.

Etiology and pathogenesis:

Hemolytic jaundice- endoglobular parasites

Hepatic jaundice- infectious hepatitis

Posthepatic jaundice- Calculosis

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(babesiosis, theileriosis);

- Cu, As intoxication - sheep

- Leptospirosis; EIAV

- Hemolytic anemia

- Resorbtion of blood from

hemorrhage- Ineffective erythopiesis

(viral)

- drug induced hepatitis

(liver toxicity)

- liver dystrophy

- cirhosis

- tumors

- parasites ( Ascaridosis,

Dicroceliosis, Fasciolosis)

- Chronic inflamation of the biliar

ducts ( colangitis, colecistitis)

- enteritis

Cholestasis is a general term for impedance of bile output from the liver.

Jaundice (icterus) is the discoloration of tissues and body fluids by an excess of bile

pigments. Jaundice can have prehepatic or cholestatic origins.

Prehepatic jaundice is usually related to overproduction of bilirubin from heme

catabolism in hemolytic disease.

Cholestatic jaundice can be hepatic or posthepatic:

- In hepatic jaundice, there may be impaired uptake, metabolism, secretion,

and transport of bile pigments within the liver.- Inposthepatic jaundice, cholestasis is related to obstruction of bile flow at

the level of the major bile ducts or gallbladder.

Hepatic causes of jaundice can be conveniently subdivided into:

(1) failure of hepatocytes to take up or conjugate bilirubin;

(2) impaired excretion and transport of conjugated bilirubin in canaliculi or ducts

within the liver;

(3) impaired function of hepatocellular adenosine triphosphate-binding cassette

transporters and aquaporins that drive the osmotic flow of bile.

The bile secretion pathway has multiple steps that can be a target of a particular

cholestatic mechanism. These include impaired uptake of unconjugated bilirubin, reduced

production of conjugated bilirubin, slow canalicular transport, leakage from the duct system,and physical obstructions at various levels within and beyond the liver.

It is common for these prehepatic, hepatic, and posthepatic causes to be combined to

various degrees in any case of jaundice.

Extrahepatic biliary obstruction initially causes increased pressure in bile ducts with

dilation and stasis of content in the smaller radicles in the portal triads. Shortly, however, the

parenchymal changes are the same as in intrahepatic cholestasis. Brown bile pigment is

present in canaliculi and hepatocyte cytoplasm. The canaliculi are distended and sometimes

loculated. The bile plugs are homogeneous. In the hepatocyte cytoplasm, initially in periacinar

zones and later in all zones, the pigment is present in large, irregular lysosomes. In long-

standing cholestasis, such as may occur with extrahepatic biliary obstruction, cholangioles

become hyperplastic and some hepatocytes become hydropic with a reticulated appearance tothe cytoplasm and are coarsely impregnated with pigment. Foci of parenchymal necrosis

release small lakes of bile that can become surrounded by macrophages and giant cells.

Gross lesions: yellowish discoloration of the mucosal and serous membranes,

connective tissue and internal organs. The recognition of jaundice at necropsy sometimes

involves differentiation of bile staining of tissues from the yellow staining caused by

accumulation of carotenoid pigments. These latter are limited to fat depots and are to be

expected in certain species such as horses. Distinction of the fatty pigments from bile depends

on the absence of the former from pale, nonfatty tissues such as periosteum and dermal

collagen.

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Hepatic jaundice

- Accumulation of multiple fine granular

bilirubin pigment (yellow- brown) in the

hepatocytes, macrophages ( Kupffercells) and endothelial cells;

- dystrophy and/ or necrosis of

hepatocytes due to excess of biliar pigment

( toxicity) in the cytoplasm

Posthepatic jaundice

- Bile accumulation in the biliary ducts -

distention of the ducts and epithelial atrophy

- presence of bile in the intralobular hepaticducts bile thrombi

- macrophages ( Kupffer cells) laden with

biliary pigments

Evolution:

- dystrophy and/ or necrosis of tissue due to biliar toxicity

- biliar cirrhosis, biliar nephrosis and neuronal injury.

Disorders of mineral metabolism:

- Calcinosis kidney, lung, arteries (calcification is a subtype)- Lithiasis or calculosis

- Pseudocalculosis

- Pathological osification ( in tumors, arteries, liver, lung )

- Decrease of calcium quantity (bone)

Renal mineralization (Dystrophic calcification of kidney)Renal mineralization (Dystrophic calcification of kidney)

Definition: kidney dystrophy due to excessive accumulation of calcium salts in the

renal tubes (basal membrane and nephrocytes).Etiology:

Metastatic calcification

- involves a systemic calcium excess imbalance

- pseudohyperparathyroidism chronic renal

failure

- primary hyperparathyroidism (benign tumors)

- hypervitaminosis D

- ingestion of plants with vitamin D like

substances ( Trisetum flavescens)

- high phosphorus diet- hypomagnesaemia

Dystrophic calcification

- in the devitalized tissue (necrosis, dystrophy)

- Old animals: abdominal aorta in cows; aortic

curve in horses, pulmonary aortic trunk and

parenchyma in dogs;

- TBC granulomas, thrombus, atherosclerosis

- worms (Trichinella spp.)

Gross lesions: irregularly surface, grayish discoloration, white strips in the cortical

(section), brittle aspect at palpation.


- basal membraneof renal tubes is thickened and blue - calcium salts deposition

- nephrocytes are enlarged, basophilic, necrotic

- basophilic, calcium cast in the lumen of the renal tubes

Evolution : isolation of the calcified foci with connective tissue or chronic renal failure

death.

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PATHOLOGY OF CIRCULATORY CHANGES PART IPATHOLOGY OF CIRCULATORY CHANGES PART I

DEFINITIONS:

General blood disorders:- Hypovolemia - a blood disorder consisting of a decrease in the volume of circulating

blood

- Anemia - a pathological deficiency in the oxygen-carrying component of the blood (of

hemoglobin, red blood cell volume, or red blood cell number)

- Hypervolemia (Pletora) - a blood disorder consisting of an increase in the volume

of circulating blood

Local blood and lymph disorders

HYPEREMIA AND CONGESTION local increased volume of blood in a

particular tissue or area.

A. Hyperemia active process resulting from augmented tissue inflow

because of arteriolar dilation; tissue is redder than surrounding areas because

of engorgement with oxygenated blood

1. Skeletal muscle during exercise

2. Sites of inflammation

B. Congestion passive process resulting from impaired outflow; systemic or

local; tissue becomes blue-red (cyanotic), as worsening congestion leads to

accumulation of deoxygenated hemoglobin

1. Systemic

2. Local

C. Congestion and edema commonly occur together: congestion of capillarybeds is related to development of edema

D. Long-standing congestion (chronic passive congestion) results in stasis of

poorly oxygenated blood and chronic hypoxia

1.May result in parenchymal cell degeneration, cell death, microscopic

scarring

2. Capillary rupture may cause small hemorrhagic foci

3. Breakdown and phagocytosis of red cell debris may result in

hemosiderin-laden macrophages

- Haemorrhage (Bleeding) the loss of blood from the circulatory system

- Ischemia a decrease in the blood supply to a bodily organ, tissue, or part

caused by constriction or obstruction of the blood vessels

- Thrombosis blood clotting (coagulation) in a blood vessel in a living animal

- Embolus - a mass, such as an air bubble, a detached blood clot, or a foreign

body, that travels through the bloodstream and lodges so as to obstruct or occlude a

blood vessel

- Infarct- an area of tissue that undergoes necrosis as a result of obstruction of

local blood supply, as by a thrombus or embolus

- Metastasis- transmission ofpathogenic microorganisms orcancerous cells

from an original site to one or more sites elsewhere in the body, usually by way of the

blood vessels or lymphatics.

Interstitial fluid disorders

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- Dehydration (hypohydration) is defined as excessive loss of body water.

- Edema (Oedema) is an abnormal accumulation of fluid in the tissue. (Categories:

Increased Hydrostatic Pressure /Reduced Plasma Osmotic Pressure, /Lymphatic

Obstruction / Sodium Retention / Inflammation)

- Hydrops - is an abnormal accumulation of fluid in the cavities (pleura, pericardium,

or in the peritoneal cavity); eg: ascites, hydrothorax, hydropericardium, hydrocephalus- Anasarca is severe, generalized edema with profound subcutaneous tissue swelling

Pulmonary congestion (hyperemia) and edemaPulmonary congestion (hyperemia) and edema

Definition: is a circulatory disorder characterized by an excessive accumulation of

blood and interstitial fluid in the lungs.

Pulmonary edema is a frequent complication of many diseases and is therefore one of

the most commonly encountered pulmonary abnormalities. If severe, pulmonary edema has a

catastrophic effect on lung function by:

- reducing pulmonary compliance,

- blocking ventilation of the alveoli,

- obstructing gas exchange across the alveolar septa,

- reducing the surface area of the air-liquid interface in the alveoli

- proteins present in the edema fluid interfere with surfactant function,

Etiology:

Active/hyperemia

- inflammatory

response

(pneumonia)

Passive/congestion

- chronic left heart

failure

Pulmonary edema

- increased venous hydrostatic pressure: chronic left heart failure,

increased blood volume, pulmonary venous oclusion

- increased permeability of the alveolar barrier: pneumonia, diffusealveolar damage, endotoxemia/septicemia

- impairment of active transport of fluid from distal airspaces: damage

to type II pneumocytes or Clara cells, hypoxia (high altitude), oxygen

and nytrogen radicals (increased by inflamation), halogenated

anesthetics, possibly lidocaine, malnutrition, high alveolar protein

content

- reduced oncotic pressure : hypoproteinemia (uncommon)

- lymphatic obstruction: neoplastic emboli in lymphatics or lymph

nodes (rare)

- neurogenic pulmonary edema secundary to brain trauma

- acute upper airway obstruction: strangulation, hanging- hypoglicemia

On gross examination, edematous lungs are wet, heavy, and do not completely collapse

when the thorax is opened, and fluid oozes from the cut surface. Edema is prominent in the

pleura and the pulmonary interstitium. In cattle and swine, the interlobular septa are obviously

distended by clear fluid. Foam often fills the trachea and bronchi and flows from the nostrils,

although this is a common incidental finding in horses and sheep dying of a variety of causes.

The color of tissue is red or burgundy and consistency is increased. The thoracic cavity may

contain excess fluid.

Histologically:- hypertrophy of alveolar interstitial space due to excessive dilation of blood vessels

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- edema fluid is acidophilic, homogeneous, or faintly granular material filling alveoli,

except for occasional discrete holes that represent trapped air bubbles.

- presence of hemosiderin laden macrophages

Histopathology is neither sensitive nor specific for detection of pulmonary edema: the

protein in edema fluid can leach from sections during processing and be quite inconspicuous;

conversely, pink material often fills the alveoli in autolysed carcasses or those euthanizedwith barbiturates. Therefore, gross examination is usually a more accurate indicator of the

presence and severity of edema than hitological examination!

Evolution : resorbtion; acute respiratory insufficiency - death; pulmonary fibrosis.

Muscle hemorrhageMuscle hemorrhage

Hemorrhage - Definition: represents a circulatory disorder characterized by the loss or

outflow of blood from blood vessels (internal or external)

Etiology:

Per rexis (rupture)

-traumatic injuries (knife,

bullet, contusions a.o.)

- Aneurisms

- Aterosclerosis,

calcinosis, hypertension

Per diabrosis (erosion)

-Parasites (horse, cat)

-increased gastric acidity -

ulcers

-chemical drugs (NaOH)

Per diapedesis

- Toxemia, viremia,

bacteriemia,, with endothelial

tropism (CSF)

-Toxicity (ANTU, warfarin)

Classification of hemorrhages:

- Petechia: 1- to 2-mm hemorrhages into skin, mucous membranes, or serosal

surfaces

-Purpura Slightly larger hemorrhages (more than 3mm)-Ecchymosis: Larger hemorrhages (>1 to 2 cm), typical after traumas

Hematoma: a localized collection of extravasated blood

Hemorrhagic diathesis: multiple hemorrhages in the whole body

Grosslesions : swelled muscle, dark-red, with blood leaking on section

Microscopicallyfindings:

- presence of multiple erythrocytes between myocytes and muscle fascicles

- presence of siderophages (macrophages containing hemosiderin pigment)

Evolution : hypovolemic shock; resorbtion; fibrosis; infection

White kidney infarctWhite kidney infarct

Definition: Infarcts of the kidney are common lesions of localized coagulative necrosis

produced by embolic or thrombotic occlusion of the renal artery or of one of its branches. The

sequelae depend on whether the obstructing material is septic or bland and on the size and

number of the vessels obstructed.

Etiology:

Thromboembolism: Occlusion of a blood vessel due to a thrombus (thrombotic

endocarditis)

Embolism: other foreign matter that gets stuck while traveling through the

bloodstream (gas following intravenous injection)- Bland thrombi produce typical infarcts;

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- Septic thrombi produce abscesses that may heal, sequestrate, or discharge into the

pelvis.

Thrombosis of a trunk of a renal artery will produce total or subtotal necrosis of

the kidney, the extent of the latter depending on the presence and efficiency of

parahilar and capsular collaterals.

If an arcuate artery is obstructed, there is necrosis of a wedge of both cortex andmedulla.

If an interlobular vesselis involved, infarction is limited to the cortex.

The ease and the frequency with which the kidneys are infarcted result from their

vascular architecture being of the "end-artery" type and the large volume of blood that

continually traverses them.

Gross lesions: Soon after total obstruction of a vessel, the related wedge of tissue is

swollen and intensely cyanotic and it is congested by the blood that oozes into the vessels

from collaterals. There is no sharp line between the infarcted zone and the adjacent normal

tissue because in the narrow boundary zone there is an outer part in which blood continues to

ooze slowly and an inner part that is more or less well served by diffusion from the viable

tissue. In the outer part of the marginal zone, the red cells survive and circulation may be re-

established, but this zone persists for the first 2-3 days; it is usually referred to, apparently

erroneously, as thezone of reactive hyperemia.

The limit of useful diffusion determines the actual limit of the infarct, and it is here that

dehemoglobinization begins, neutrophils accumulate, and the area of total necrosis begins.

The dehemoglobinization begins from the periphery at about 24 hours and may be complete

in 2-3 days, the infarcted area then being white. Before decoloration begins, the area that

will be affected is outlined by a thin but distinct white line of leukocytes.

Commonly, infarcts of various ages in a kidney indicate recurrent embolic episodes.

Microscopicallyfindings: 3 different areas:

1. central: coagulation necrosis (pale nuclei and cells)2. leucocytes (PMN neutrophils and macrophages ) infiltrate

3. area with congestion and hemorrhage surrounded by normal tissue

Evolution: The necrotic zone is progressively replaced by fibrous tissue, and healed

infarcts persist as pale gray-white scars, wedge-shaped and much depressed below the

surface. The scars may be difficult or impossible to distinguish grossly from focal healed

pyelonephritis.

.

PATHOLOGY OF CIRCULATORY CHANGES PART IIPATHOLOGY OF CIRCULATORY CHANGES PART II

Hepatic venous THROMBUSHepatic venous THROMBUS

Definition: A clot consisting of fibrin, platelets, red blood cells, and white blood cells

that forms in a blood vessel or in a chamber of the heart in a living animal, and can obstruct

the blood flow.

Aetiology:

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Local thrombosis - Virchow's triad:

-Endothelial injury (e.g. trauma, atheroma)

-Abnormal blood flow(loss of laminar flow

resulting from stasis in veins or turbulence

in arteries) (e.g. valvulitis, aneurysm)

-Hypercoagulability (e.g. leukaemia, FactorV mutation )

Disseminated intravascular coagulation

(DIC):

-widespread microthrombi formation

-hemorrhagic and ischaemic necrosis of

tissue/organs (septicaemia, acute leukaemia,

shock, snake bites, fat emboli from brokenbones, or other severe traumas).

Virchow's triad in thrombosis.Endothelial integrity is the most important

factor. Injury to endothelial cells can alter

local blood flow and affect coagulability.Abnormal blood flow (stasis or turbulence),

in turn, can cause endothelial injury. Thefactors promote thrombosis independently or

in combination (Robins and Cotran,Pathologic basis of disease)

Gross lesions - must be differentiated from post-mortem blood clotting

Thrombus

-adherent to the endothelial wall

-mat-friable

-irregular

-non-homogenous colour

Post-mortem clott

-non-adherent to the endothelial wall

-shiny-elastic

-regular surface (mold of the blood vessel)

-homogenous colour(dark red)


- in the vascular lumen, the thrombus mass has a globulous shape, formed of:

- Fibrin filaments with concentric disposal

- Blood cells (red blood cells, white blood cells, platelets) between the fibrin

filaments

- The thrombus area adherent to the wall: presence of good vascularised young

connective tissue (fibroblasts, small blood vessels and colagen)

- White blood cells barrier

Evolution: If a patient survives the initial thrombosis, in the ensuing days to weeks

thrombi undergo some combination of the following events:

Propagation.

Embolization.

Dissolution (the result of fibrinolysis)

Organization and recanalization (by the ingrowth of endothelial cells,

smooth muscle cells, and fibroblasts)

infection

calcification, hyalinisation

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Complications: Thrombi cause obstruction of arteries and veins, and are sources of

emboli.

- Venous thrombi can cause congestion and edema in vascular beds

distal to an obstruction, but they are far more worrisome for their capacity to

embolize to the lungs and cause death.

- Arterial thrombi can embolize and cause downstream infarctions, athrombotic occlusion at a critical site (e.g., a coronary artery) can have more serious

clinical consequences.

Acute and passive liver congestionAcute and passive liver congestion

Definition: is a circulatory disorder characterized by increase of blood in the venous

system of the liver (increase in the venous blood pressure compared to portal pressure)

Etiology:

-formation of thrombus, abscess, neoplasm or parasites in the caudal cave vein

-right heart failure, pericardial effusions, constrictive pericarditis

-hepatic lobe torsion (local congestion) due to diaphragm hernia

-broiler chicken ascites

Gross lesions:

Acute liver congestion

-hypertrophy (round margins and distended

Glisson membrane)

-red darkcolor

-marked lobular structure with distended central

vein surrounded by a yellowish colour (steatosis)-blood present on the cut surface

-regular surface

-portal veins are dilated

-erythrodyapedesis leading to red abdominal

efusion, rich in fibrinogen (clots on the liver

surface)

Chronic liver congestion

-hypertrophy with irregular and

thicker surface (fine nodular surface)

-opaque colour(due to fibrous

connective tissue organized in fibrous

plaques)-marked lobular structure with

distended central vein surrounded by a

yellowish color (steatosis)

-blood present on the cut surface

-increased consistency

In acute hepatic congestion, the central vein and sinusoids are distended; centrilobular

hepatocytes can be frankly ischemic while the periportal hepatocytesbetter oxygenated

because of proximity to hepatic arteriolesmay only develop fatty change. In chronic

passive hepatic congestion the centrilobular regions are grossly red-brown and slightly

depressed (because of cell death) and are accentuated against the surrounding zones of

uncongested tan liver (nutmeg liver). Microscopically, there is centrilobular hemorrhage,

hemosiderin-laden macrophages, and degeneration of hepatocytes. Because the centrilobular

area is at the distal end of the blood supply to the liver, it is prone to undergo necrosis

whenever the blood supply is compromised.

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Acute liver congestion:

-Central veins, spaces of Disse and

central vascular sinusoids are

dilated (filled with erythrocytes),compressing the hepatocytes which

are atrophied

-Mediolobular and periportal

hepatocytes may present fatty

change (hypoxic mechanism);

Chronic liver congestion:

-Central veins, spaces of Disse and central vascular

sinusoids are dilated, compressing the hepatocytes

which are atrophied and, with progression, will necrotize(loss of hepatocytes) - central hemorrhagic necrosis

(compression and/or ischemic mechanism).

-Central veins fibrosis

-Reversed liver aspect

-Presence ofhemosiderin (erithrolysis) and

macrophages engulfing this pigment (siderophages)

Differential diagnose:

Infectious hepatitis of dogs (Rubarth) centrolobular necrosis, congestion,

hemorrhage, no steatosis at the periphery

Perilobular steatosis with other etiology Perilobular necrosis : rabbit calicivirus (haemorhagic disease of rabbits),

ischemia no centrolobular severe congestion

Evolution :

- fibrosis

- cirhosis

- hepatic carcinoma

- death by liver insufficiency.

INFLAMMATIONINFLAMMATION

DEFINITION: Inflammation represents a reaction of the connective-vascular tissue

towards an agression designed to:

- eliminate the agressive agent

- repair the damaged tissue through cicatrisation

Inflammation is THE defense reaction of an organism to an aggression (without it the

survival would not be possible).

The aggressive agents can be very diverse:

Physique factors : cold, heat, radiations, trauma

Chemical factors

Pathogenic agents : bacteria, virus, parasites Immunologic events

It represents as well an important cause of tissue lesions (from here the interest for the

use ofanti-inflammatory drugs destined to combat or regulate).

CLASIFICATION

Morphopatologic:

1. Alterative: Brutal action of factors (physical, chemical, biological) with a minimum

vascular reaction.NECROSISthe main process.

descuamative (cataral) - (if epithelium is affected)

necrotic (tissue and parenchimatous organs):

o liquefactiono coagulation

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o caseification

gangrenous (severe necrotic process with none or minimal

reaction)

o dry

o humid

o gassy2. Exudative: Exudate = apathological complex composed from a liquid fraction

(plasma with different amounts of proteins) and a cellular component (blood cells).

serous (high proteic content clots in contact with air)

hemorrhagic (exudate is rich in red blood cells)

purulent(suppurative)-(exudate rich in neutrophils and bacteria)

o purulent catar

o diffuse

o abscess

o phlegmon

o empyema fibrinous (false membrane) - (exudate is rich in fibrinogen

which converts to fibrin)

o simple (exudate does not adhere to tissue)

o fibrino-necrotic(diphtheroid)(exudate adheres to tissue)

3. Proliferative: are characterized by predomination of cell proliferation, with the

presence of mononuclear cells (hystiocytes, lymphocytes, plasma cells, mast cells,

macrophages/epitheloids, giant cells) polimorphonuclear (PMN) cells (neutrophils,

eosinophils). They are produced especially by agents that act slowly.

Epitheloid and giant cells originate from macrophages so they have phagocytotic and

pinocytotic functions. Epitheloids are cells with large nucleus, rich in cytoplasm, without a

clear demarcation of cell borders, due to cytoplasm elongations. Giant cells present numerousnuclei, with an abundant cytoplasm, and their morphology and nuclear pattern largely

depends on the etiological agent.

granulomatous (with macrophages and epithteloid-giant cells)

o n foci (granuloma)

o difuse

interstitial

o limpho-histiocitic

o eozinophilic

o fibrous

o limpho-plasmociticEvolution:

- Peracute

- Acute

- Subacute

- Chronic

Etiology:

Physique factors : cold, heat, radiations, trauma

Chemical factors

Pathogenic agents : bacteria, virus, parasites

Immunologic events

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ALTERATIVE INFLAMMATIONSALTERATIVE INFLAMMATIONS

Necrotic hepatitis (diffused and miliar)Necrotic hepatitis (diffused and miliar)

Definition: An alterative inflammation of the liver characterized by the necrosis of the cells in

the affected area and the presence of a leukocyte reaction.

Etiology:

- Chemical factors(CCl4), toxicfactors(aflatoxins).

- biological agents: viruses (Adenovirus DIH - dog infectious hepatitis, chicken,

turkey, Calicivirus - haemorhagic disease of rabbit (HDR), Picornavirus - youngducks,

Parvovirus young geese, Herpesvirus Aujeski disease), bacteria (Necrobacilosis,

Leptospirosis, Clostridiosis, Campilobacteriosis, Salmonelosis, Pasteurelosis, Colibacilosis,

Listeriosis, Chlamidiosis a.o.) and parasites (Trichomonas, Histomonas)

Gross lesions:Diffuse (Rabbit

Calicivirus)

- lobulation evident

- spread whitish color

due to necrotized

hepatocytes around the

centrolobular area

Large foci (Necrobacilosis

Trichomonosis, Histomonosis)

- unique or multiple large

necrotic foci (1-3cm) on the surface

and in the parenchyma

- discoloration (yellow grayish

area) friable and dry, surrounded by a

congestive ring (red-violet) which

delimits the healthy parenchyma

Millar foci

(fowl cholera, salmolesosis in

young animals, Aujeski disease

)

- small (mm.), multiple,

necrotic foci on the surface

and in the hepatic

parenchyma

- color: white-yellow


Diffuse necrotic hepatitis

- destroyed liver architecture

- coagulation necrosis mainly at the periphery of the

lobules (cells are pale, with nuclei like shadows)

- remains of necrotized cells

- presence of inflammatory cells: mainly neutrophils

and macrophages

Miliar necrotic hepatitis

-areas of pale color (coagulation

necrosis) with inflamatory infiltrate,

congestion and remains of the

distructed cells

Evolution : depends on the etiological agent, extent of necrosis and animal resistance. The

main possibilities of evolution are:

- destruction of a large surface of the liver acute liver insufficiency death (DIH,

HDR)

- healing ad integrum (in case of small necrotic foci, and when the causing agent stops

acting)

- fibrosis cirhosis (larger areas of necrosis)

- infection of the necrotic area (with formation of abscesses or gangrenes).

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Chronic gastric ulcer (Chronic ulcerative gastritis)Chronic gastric ulcer (Chronic ulcerative gastritis)

Definition: is a excavation of the stomach surface due to mucosal necrosis which

penetrates the muscularis mucosae and muscularis propria, produced by acid-pepsin

aggression or by other factors.

Gastroduodenal ulcer produces signs much less often in animals than in humans. Thepathogenesis of peptic ulcer in both humans and animals in general seems to resolve into a

relative imbalance between the necrotizing effects of gastric acid and pepsin on one hand,

and the ability of the mucosa to maintain its integrity on the other. Impairment of mucosal

integrity in the face of normal acid secretion is probably the predominant mechanism,

although there are clear instances when hypersecretion of acid is causative.

Etiology:

1. Factors implicated in hypersecretion of acid include:

- abnormally high basal secretion,

- increased histamine levels associated with mastocytosis or mastocytoma

- Gastrinomas (Zollinger Ellison syndrome), rare gastrin-secreting tumors

2. Ulceration due to compromise of mucosal protective mechanisms attributed to:

- Nonsteroidal anti-inflammatory drugs (NSAIDs), such as

aspirin, phenylbutazone, indomethacin, naproxen, ibuprofen, flunixin

meglumine, and pyroxicam.

- In humans, gastritis associated with Helicobacter pylori

infection, and duodenal colonization with this agent, are associated with

development of duodenal ulcer. Helicobacter-associated gastritis extending

cranially in the stomach is associated with gastric ulcer. Similar

associations between Helicobacter infection, gastritis, and peptic ulcer have

not been demonstrated convincingly in domestic animals.

-

Reflux of duodenalcontents containing bile salts- Glucocorticoids in high doses as antiinflammatory,

immunosuppressive, or antineoplastic therapy

- "Stress"; trauma or major surgery; in dogs following spinal

trauma

- Administration ofmethylprednisolone sodium succinate to dogs.

Abomasal ulcers in cattle are common.

Gastric ulcer in swine is usually restricted to the pars esophagea.

In horses, ulcers in the stomach of.foals and adults are often found at autopsy incidental

to some other disease process.

Grossly, whatever the cause, the results of a breach of the gastric glandular mucosa

have the potential to follow a common pathway to ulceration in all species. Acutesuperficial lesions, such as those associated with stress or following administration of aspirin,

are often seen as areas of reddening and hemorrhage, especially along the margins of rugae

in the fundic mucosa. Acid treatment of haemoglobin gives blood on the surface or in the

gastric lumen a red-brown or black color. In some instances, melena, presumably the result of

a recent episode of gastric bleeding, may be present in the lower intestine, with minimal gross

evidence of hemorrhage or ulceration in the stomach. The microscopic lesion associated with

hemorrhage of this type is often subtle; bleeding seemingly results from diapedesis, with

minimal mucosal damage.

Lesions of any genesis proceeding to gastric ulcer do so by progressive, often rapid,

coagulative necrosis of the gastric wall. Ulcers vary in microscopic appearance depending

on their aggression, and the point in their development at which they are intercepted:

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- Acute gastric lesions appear as erosions with superficial eosinophilic

necrotic debris and loss of mucosal architecture to the depths of the

foveolae, or as a depression in the mucosal surface with necrotic debris at

the base. Necrosis usually extends rapidly to the muscularis mucosae,

causing ulceration.

-Subacute to chronic ulcers have a base and sides composed of granulationtissue of variable thickness and maturity, infiltrated by a mixed

inflammatory cell population, and overlain by a usually thin layer of

necrotic debris. The layer ofgranulation tissue may be thick and mature, or

thinner, less mature, and with superficial evidence of recent necrosis. There

is mucous metaplasia and hyperplasia inglands at the periphery of the

ulcer, epithelial cells may gradually migrate across, closing the defect.

Thrombosed arterioles and venules are often seen, associated with anemia

or obvious hemorrhage.

Signs associated with peptic ulcerinclude: variable appetite, abdominal pain, vomition,

melena, and anemia.

Evolution: Ulcers attaining the submucosa impinge on arterioles of increasingdiameter, multiplying the risk of significant gastric hemorrhage. The ulcer may progress

through the muscularis and serosa, culminating in perforation of the gastric wall with

consecutive peritonitis or/and death. Perforating duodenal ulcer may instigate pancreatitis.

Pyloric and duodenal stenosis has been associated with healing ulcers, as well as anemia.

EXUDATIVE INFLAMMATIONSEXUDATIVE INFLAMMATIONS

Fibrinous pneumonia (Lobar pneumonia)Fibrinous pneumonia (Lobar pneumonia)

Definition: A predominantly exsudative inflammation of the lung produced mainly by

bacterial agents. It is characterized by the formation at the level of epithelium, serosa and

parenchyma of some false fibrin membranes (whitish with dirty-yellow nuances, sometimes

brown if they are infiltrated with neutrophils). These membranes do not adhere to the deep

plans, and can be easily detached or expectorated by cough (tracheo-brochial localisation).

Etiology: The disease is produced by bacterial germs: Pasteurella spp., Mycoplasma

spp., Bordetella spp, Haemophilus spp., Bordetella spp., Corynebacterium spp,

Staphylococus spp..

Fibrinous pneumonia has a gradually evolution, both grossly and histologically. Due to

the different stage evolution, the lung can present different aspects (stages) even from lobuleto lobule, thus giving the mosaic aspect of the lung (grossly).

The following stages, are representative for the evolution of fibrinous pneumonia in

horses, where the different stages are easier recognized, due to the lungs anatomo-histology.

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Gross lesions: Microscopically findings:

Stage I - Pulmonary congestion and oedema

- the lungs are wet, heavy, the colour is red or

burgundy and consistency is increased

- in trachea, bronchi and pulmonary tissue is

present a pink or red foamy fluid

Stage II - Red hepatization

- consolidation of tissue into a liverlike mass,

with a red-brown color

Stage I

-hypertrophy of alveolar interstitial space due

to excessive dilation of blood vessels;

- in alveoli is present an homogenous

acidophilic edema fluid and air bubbles

Stage II

-presence of red (oxifil) fibrin masses in the

alveolar lumen, with rare blood cells

-septal congestion

Stage III - Gray hepatization

- consolidation of tissue into a liverlike mass, with

a brown-graysh colour

Stage IV - Resolution stage

- Soft-pasty consistency, gray-yelowish colour

- On section, a pus-like liquid is expressed

More stages can co-exist on an animal

Stage III

-presence of red fibrin masses in the

alveolar lumen, with abundhent leucocytes

-mild septal congestion

Stage IV

-fibrin is destroyed and alveolar content is

represented by cells, neutrophils and

macrophages, old/necrotized cells,

Evolution :

- death-due to asfixia, septicemia or other complicatins

- spontaneous resolution rarel- necrosis with incapsulation of the affected area

- supuration

- sclerosis

- obstructive bronchiolitis

*** In our slides we observe also a superposed bacterial infection. Thus, beside septal

congestion and the red fibrin masses with mononuclear cells in the alveolar lumen, we also

have present an important purulent exudate in the lumen of bronchioles and in the

surrounding alveoles.

Purulent (suppurative) leptomeningitisPurulent (suppurative) leptomeningitis

Definition: Inflammation of leptomeninges which is caused by a variety of purulent

bacteria.

Leptomeningitis can be classified according to etiology (e.g., bacterial, mycotic),

according to duration (e.g., acute, chronic), and according to the type of exudates (e.g.,

fibrinous, purulent). Classification by type of exudate is very useful, not only because it

indicates the expected histologic lesions, but also clinically because it indicates the possible

etiology.

Purulent meningitis is by far the most common meningitis in domestic animals,

especially neonates.

Purulent leptomeningitis may arise:

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- by direct extension from an adjacent structure. Extension from an

epidural abscess or inflammation may result in diffuse leptomeningitis but, in most

of the few cases of this origin, the leptomeningitis is local and overshadowed by the

brain abscess that usually forms

- by local extension from a brain abscess, either by direct permeation or

by spread in the Virchow-Robin spaces (in listeriosis and in association with verylarge cerebral abscesses)

- by hematogenous origin,

- thromboembolic lesions and leptomeningitis complicated by

choroiditis,

- lymphogenous infection (rarely).

Etiology: Lysteria spp., E. coli., Streptococus (suis, pneumonie), Staphylococcus,

Haemophylus, Pneumococus, Salmonella spp.,Mannheimia haemolytica and P. multocida.

Once infectious agents gain access to the leptomeninges there is little resistance to

spread in the meningeal spaces, and the inflammatory process becomes more or less diffuse in

most cases.

The apparent gross distribution of meningitis varies somewhat with the cause. In thefirst day or so of suppurative meningitis before exudation is clearly recognizable, the

meninges may be faintly opaque and hyperemic. After a few days, the appearance of the

brain and cord is typical. The basal cisterns that accumulate the most exudate are filled with

creamy pus or with gray-yellow fibrinopurulent exudate. The extreme exudation in these

cisterns is due in part to their large size but in part also to sedimentation of particulate

exudate. The exudate is in the arachnoid spaces and there is little if any on the outer surface of

this membrane. The arachnoid appears stretched. It is easy to overlook even copious

exudates because their color is not very different from that of the brain. A useful clue is

that even the largest basilar vessels and the trunk of the oculomotor nerve are partially or

completely buried and obscured by exudate.

Over the hemispheres the exudate is usually confined to the fissures, where the

arachnoid space is wide, and spares the surfaces of the gyri, where the arachnoid space is

narrow.

The severe degree of exudation described above is what is usually seen in animals. On

careful inspection by naked eye, almost every case of purulent meningitis can be detected but

the microscope may be necessary to confirm some cases.

The brain is swollen in every acute case of pyogenic meningitis, and the swelling is

frequently severe enough to cause displacement with coning of the cerebellum. The edema

affects the white matter. It is possible that obstruction of the meningeal orifices of Virchow-

Robin spaces by exudate and stasis of flow of meningeal fluid may contribute to the edema.

The brain itself is normal except for softness and swelling and the rare cortical infarcts in thecerebrum or cerebellum.

Microscopically, purulent meningitis does not differ in its character from pyogenic

inflammation in other loose tissues, such as the lung. A few mononuclear cells are mixed with

a very large number of neutrophils in the arachnoid spaces acompanied by hyperemia of

meninges.

The amount of fibrin in the exudate varies. There may be some infiltration for a short

distance along the Virchow-Robin spaces about veins.

The pia mater as a rule remains intact, and it is only in exceptional cases that some

microbial activity is observed in the adjacent parenchyma, or the pia is eroded to allow

neutrophils to invade the surface of the brain, showing spongy change or vacuolization due to

edema.Evolution/Complications: meningitis spreads to the brain and cord.

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Whether encephalitis develops by spread of meningitis may be largely a question of

time.

Internal hydrocephalus is a sequel to ependymitis and occlusion of the aqueduct, as a

result of which the lateral and third ventricles are dilated.

Chronic pyogenic leptomeningitis is rarely observed in animals. The process may

sterilize itself or be sterilized by antimicrobials, but much of the injury is established in theearly stages of the process and, once the diagnosis is evident clinically, death is the expected

outcome. The early injury is exaggerated by the persistence of exudate even after the infection

is controlled because there is no free drainage from the meningeal spaces.

Healing occurs only after there has been considerable destruction of the meningeal

framework with repair byfibrous tissue.

Pulmonary abscessPulmonary abscess

Definition: a collection of pus that has accumulated in a cavity formed by the tissue on

the basis of an infectious process, usually caused by bacteria.

Etiology:

- Anaerobic and aerobic bacteria: Bacteroides, Fusobacterium species,

Streptococcus spp., Staphylococcus, Klebsiella, Haemophilus, Pseudomonas,Nocardia,

Escherichia coli, Streptococcus, Mycobacteria.

- Fungi: Candida, Aspergillus.

- Parasites:Entamoeba histolytica.

Pulmonary abscesses usually arise either from chronic bronchopneumonia or from

septic emboli lodging in the pulmonary vessels. A cranioventral location and associated

bronchiectasis are evidence of origin from bronchopneumonia.

Multiple, widely distributed abscesses usually indicate hematogenous origin and areoften associated with an obvious source of septic emboli elsewhere in the body, such as

endocarditis orhepatic abscesses withphlebitisofthehepaticveinincattle. The occurrence

of abscesses in other tissues supports a hematogenous route of infection. Other causes of

pulmonary abscess include aerogenous fungal infections that often have a disseminated

pattern, aspirated foreign bodies such as plant awns, direct traumatic penetration of the lung,

and specific hematogenous infections such as caseous lymphadenitis and melioidosis.

It is often impossible to determine the pathogenesis of isolated abscesses, if lesions are

not identified in other tissues.

Gross lesions: usually round or oval shape collection of pus, well delimited by fibrous

membrane, with different colors (yellow, black, green-blue). Presence of purrulent material on

the cut surface.Microscopically findings:

There are 3 typical areas:

1. necrotic purrulent area in the centre with granular aspect(dead cells,

neutrophils, and bacteria)

2. leucocyte barier (neutrophils and macrophages)

3. fibrous membrane

Evolution: Abscesses may erode through the pleura to cause empyema, through blood

vessels to cause massive blood loss, or into a bronchus to cause fatal airway obstruction or

fulminant suppurative bronchopneumonia.

Complications: septicemia, metastasis, membrane lysis (internal or external).

Healing by fibrosis/calcification.

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PROLIFERATIVE INFLAMMATIONSPROLIFERATIVE INFLAMMATIONS

Echinococcus Hydatid CystEchinococcus Hydatid Cyst

Taeniid tapeworms

Taeniid cestodes are the most important tapeworms in domestic animals, not because of

the effects of the adult worm in the carnivorous definitive host, but rather due to the

metacestodes, or larval forms, in intermediate hosts. Single oncospheres hatch from the egg in

the upper small intestine, penetrate the epithelium, and are carried in the portal blood to the

liver. Some species of metacestodes migrate in the liver, eventually to enter the peritoneal

cavity. Others persist to develop in the liver, while still others pass on to the heart, lungs, and

systemic circulation, establishing in muscle or a variety of other sites and tissues.

Metacestodes may occasionally be found in organs other than the site of predilection.

Taeniid metacestodes assume four basic forms.

- The cysticercus is a fluid-filled, thin-walled, but muscular cyst, into which thescolex and neck of a single larval tapeworm are invaginated.

- The strobilicercus is a modification of this theme; late in larval development

the scolex evaginates and is connected to the terminal bladder by a segmented strobila,

so that it resembles a tapeworm, several centimeters long.

- The coenurus is a single or loculated fluid-filled cyst, in which up to several

hundred nodular invaginated scolices are present in clusters on the inner wall. Each

scolex is capable of developing into a single adult cestode in the intestine of the

definitive host.

- The hydatid cyst is a uni- or multilocular structure, on the inner germinal

membrane of which brood capsules develop. Within the brood capsules, invaginated

protoscolices form. Brood capsules may float free in the cyst fluid, where they aretermed "hydatid sand." Internal daughter cysts can develop. Release of brood capsules

or protoscolices into tissues, as a result of rupture of the hydatid cyst, may lead to

development of new cysts. The alveolar hydatid cyst proliferates by budding

externally.

Echinococcus spp. tapeworms occur in the small intestine of a number of species of

carnivores, predominantly canids. In enzootic areas, the distinctive metacestodes, or hydatid

cysts, are commonly found in normal or accidental intermediate hosts. Humans may

accidentally become infected with the metacestode, and echinococcosis or hydatidosis is a

significant public health problem where carnivores shedding Echinococcus eggs come in

close contact with humans.

The species are E. granulosus, E. multilocularis, E. oligarthus, and E. vogeli. The latter

two involve sylvatic cycles in Central and South America, with felids and canids as definitive

hosts respectively, and rodents as intermediate hosts in which polycystic hydatidosis occurs;

E. uogeli may infect humans.The other two species may use domestic animals as definitive

hosts, and will be considered further here.

E. granulosus uses the dog and some other canids as the definitive host. The most

widespread strain or genotype uses a sheep--dog cycle, and has been disseminated wherever

there is pastoral husbandry of sheep. It is significant as a potential zoonosis in many parts of

Eurasia and the Mediterranean region, some parts of the UK, North America, South America,

continental Australia, and Africa. Eradication has been accomplished, or virtually so, in

Iceland, New Zealand, and Tasmania. Other cycles affecting domestic animals include horse-;cattle-; camel-; pig-; water buffalo-; goat-, and human-dog. Sylvatic cycles include: in Eurasia

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and North America, cervid-wolf~ in Argentina, hare-fox; in Sri Lanka, deer-jackal; in

Australia, macropod- dingo. Not all cycles represent different genotypes.

In the small intestine of the definitive host, protoscolices evaginate and establish

between villi and in the crypts of Lieberkuhn. The scolex distends the crypt and the

epithelium is gripped by the suckers and occasionally eroded, but there is little or no

inflammatory response. The worms that develop are short, usually less than 6-7 mm long.They commonly have only 3-5 proglottids, the caudal gravid one making up almost half the

length of the worm.

Enteric signs are not normally encountered in dogs with intestinal hydatid tapeworms.

Penetration of oncospheres released from eggs in the intestine of the intermediate host takes

them into the subepithelial capillaries, or perhaps the lacteal. The majority probably migrate

via the liver, some carrying on to the lungs and general circulation. However, those gaining

the lacteal may bypass the liver, entering the vena cava with the lymph, and either are filtered

out in the pulmonary circulation or are disseminated. Hydatid cysts occur most commonly

in the liver and lung, with some strain and host species variation in the relative prevalence in

these organs. In sheep they may be more common in lungs, while in cattle and horses, the

liver is the usual site of establishment. Less commonly in domestic animals, the brain, heart,bone, and subcutaneous tissue may be sites of development of hydatid cysts. A single cyst, or

up to several hundreds, may be present, displacing tissue in infected organs. Disease is rarely

attributed to hydatidosis in animals, even in those heavily infected. However, strategic

location of one or more cysts may lead to heart failure, bloat or central nervous signs.

Condemnation of infected organs at meat inspection causes economic loss.

Gross lesions: Hydatid cysts are usually spherical, turgid, and fluid-filled. They

usually measure 5-10 cm in diameter in domestic animals; rarely, cysts in animals may be

larger, but in humans hydatid cysts can become huge. On the other hand, some fertile cysts in

equine livers may be as small as 2-3 mm across. The lining of fertile cysts is studded with

small granular brood capsules, which contain protoscolices; and"hydatid sand," comprised of

free brood capsules and protoscolices, is in the fluid. The lining of sterile cysts is smooth.

Though the potential exists for development of internal daughter cysts, and rare exogenous

budding by herniated cysts, most hydatid cysts in domestic animals are unilocular. However,

they may be irregular or distorted in shape due to the variable resistance of parenchyma and

portal tracts or bronchi and by the profiles of bone or other resistant tissues.

Microscopically, immature hydatid cysts are surrounded by an infiltrate of mixed

inflammatory cells, including giant cells and eosinophils. As they develop, a layer of

granulation tissue, which may contain round cells and eosinophils, invests the cyst, and this

evolves so that the inner portion of the fibrous capsule is comprised of mature collagenous

connective tissue that is relatively acellular. Within this, and in close apposition, is the

acellular lamellar hyaline outer layer of the hydatid cyst wall, comprised of a polysaccharide-protein complex, which, with time, may become hundreds of micrometers thick. The cyst is

lined by the thin syncytial germinal layer from which the brood capsules form on fine

pedicles. If the cyst is ruptured and protoscolices are released into tissue, secondary cysts may

form from them.

Evolution: Hydatid cysts may degenerate.The inner structures collapse, and the mass

becomes caseous and may mineralize. Degenerate hydatid cysts grossly may resemble

tuberculous lesions or metastatic squamous cell carcinoma. Death following the break (due

to anaphylactic shock) could also occur, and paresis or paralysis due to nerve compression is

another possibility.

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ActinobacillosisActinobacillosis

This is a disease mainly of cattle, sheep, and pigs, leading to stomatitis, glossitis,

lymphadenitis, and sometimes pyogranulomas in the wall of the forestomachs of ruminants.

Actinobacillus lignieresiiis part of the normal oral flora, and in cattle is associated with

deep stomatitis. When introduced into the submucosa, it causes pyogranulomatousinflammatory loci centered on club colonies containing gram-negative coccobacilli.

Morphologically similar lesions may be caused by a variety of organisms. Arcanobacterium

pyogenes may be isolated from lingual ulcers and granulomas in lambs.

Microscopic examination of these lesions reveals well-demarcated submucosal

granulomas with plant fibers in the center, surrounded by a marked neutrophilic reaction. The

organisms most likely gain entry after the mucosa is damaged by hard fibrous plant fibers

from the weed lambsleeve sage (Salvia reflexa), present in the bedding.

Actinomyces bovis, a gram-positive filamentous organism, causes pyogranulomatous

mandibular and maxillary osteomyelitis in cattle, and mastitis in sows. Staphylococci may

cause pyogranulomatous lesions (botryomycosis) in any species, especially mastitis in sows.

Less common causes of similar microscopic lesions include Nocardia and the various agents

associated with mycetomas

Gross lesions: Actinobacillosis is typically a disease of soft tissue, spreading as a

lymphangitis and usually involving the regional lymph nodes. This distinguishes it from

actinomycosis, which causes bone lesions. The tongue is often involved in actinobacillosis,

and the chronic condition produces clinical "wooden tongue."

Entry of actinobacilli to the tongue may be gained through traumatic erosions along its

sides, but often the primary lesion is in the lingual groove. Here, trapped grass seeds and awns

may provoke the initial trauma. Lesions elsewhere in the soft tissue of the mouth may be

attributed to disruption of the mucosa by similar types of insults, and eruption of, or abrasion

by, teeth.Although actinobacillosis in cattle is best known as a disease of the tongue, the infection

may occur in any of the exposed soft tissues, especially those of mouth and esophagus;

occasionally it involves the wall of the forestomachs, the skin, or the lungs. Lesions in these

sites resemble those described in the tongue.

Actinobacillosis causes regional lymphadenitis. The cut surface of the node reveals

small, soft yellow or orange granulomatous masses, which project somewhat above the

capsular contour and which contain "sulfur" granules.There is also sclerosing inflammation of

the surrounding tissues, which may cause adhesion to overlying skin or mucous membranes.

The retropharyngeal and submaxillary nodes are most often affected, as well as the lymphoid

tissues of the submucosa of the soft palate and pharynx. Involvement of the pharynx and the

retropharyngeal lymph nodes may cause dyspnea and dysphagia.Microscopically, the lesion is a pyogranuloma, centered on a mass of coccobacilli,

surrounded by radiating eosinophilic clubs made up of immune complexes. The club colonies,

in turn, are surrounded by variable numbers of neutrophils, and are invested by macrophages

or giant cells. Lymphocytic and plasmacytic infiltrates are present in the surrounding reactive

fibrous stroma or granulation tissue. An individual inflammatory focus appears grossly as a

nodular, firm, pale, fibrous mass a few millimeters to 1 cm in diameter, containing in the

center minute yellow "sulfur" granules, which are the club colonies.

Lymphogenous spread is common. Affected lymphatics are thickened, and nodules are

distributed along their course. This distribution is best seen beneath the mucosa of the dorsum

and the lateral surface of the tongue and often can be traced through to the pharyngeal

lymphoid tissue. Some of these more superficial nodules erode the overlying epithelium, andcoalescence may produce quite large ulcers. The most common form of lingual

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actinobacillosis consists of granulation tissue in which are embedded many small abscesses

surrounded by a dense connective tissue capsule.

The epithelium overlying these large granulomas may be intact or ulcerated. Diffuse

sclerosing actinobacillosis of the tongue (wooden tongue) is firm, because of extensive

proliferation of connective tissue, which replaces the muscle fibers. Granulomatous nodules

are sparsely scattered in the fibrous stroma.Oral actinobacillosis in swine causes lesions similar to those in cattle, including

glossitis. Actinobacillosis may also occur sporadically or as outbreaks in sheep, but in this

species the tongue seems to be exempt. The characteristic lesions in sheep occur in the

subcutaneous tissue of the head, especially of the cheeks, nose, lips, and submaxillary and

throat regions, and on the nasal turbinates. They may also occur on the soft palate and

pharynx as complications of wounds received at drenching. The organism has been isolated

from a horse with a greatly enlarged tongue.

Evolution: fibrosis, fistulization, wooden tongue.

TuberculosisTuberculosis

Bovine tuberculosis, caused byMycobacterium bovis, is a chronic disease characterized

by caseating granulomas in lung, lymph nodes, and other organs. Control programs have

minimized the occurrence of bovine tuberculosis in many developed countries. The disease is

rare in Canada, the USA, and Australia, although infected wildlife reservoirs remain and cases

continue to occur in domestic livestock.

Most recent reports of bovine tuberculosis in the USA and Canada have occurred in

farmed cervids or in localized geographic areas. In most of Europe, fewer than 0.4% of herds

are infected, but the prevalence is higher in Ireland, Spain, and Italy. In contrast, bovine

tuberculosis is endemic in New Zealand and many, but reportedly not all, countries in Africa,Asia, Central and South America; 10-35% of herds are infected in many of these endemic

areas.

In many countries, the success of tuberculosis eradication schemes is complicated by

wildlife reservoirs, which maintain infection and transmit disease to cattle.

Many mycobacteria persist in soil for prolonged periods, and the infectivity ofM. bovis

is likely maintained for several weeks in the environment. However, because oral infections

require high doses of bacilli, the importance of environmental survival in the epidemiology of

disease is likely limited.

The classical tubercle bacilli are

-M. tuberculosis (human),

-M. Bovis (bovine), and-M. avium (avian) .

Two other closely related species are M. microti from voles and M. africanum.

Differing strains of M. Avium are now commonly included with strains of the very closely

related M. intracellulare as theM. avium-intracellulare complex.

To avoid confusion surrounding the term tuberculosis, convention limits it to diseases

caused by M. tuberculosis or M. bovis.

The three main species of tubercle bacilli, M. tuberculosis, M. bovis, and M. avium,

occur most frequently in their respective hosts, but cross-infections do occur and various other

species of animals are affected.

Bovine tuberculosis refers mainly to disease in cattle caused by Mycobacterium

bovis, but the term is also used to describe the pathogenic effects of this agent in other hosts.The host range ofM. bovis is broad, including cattle, deer, elk, bison, buffalo, goats, camels,

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llamas, swine, elephants, rhinoceros, dogs, foxes, cats, mink, badgers, and nonhuman and

human primates. Natural diseases most common in cattle, cervids, humans, and swine.

M. avium causes mycobacteriosis chiefly in birds and is occasionally found in cattle,

swine, horses, sheep, and monkeys.

M. tuberculosis is chiefly responsible for tuberculosis in humans, and occasionally

infects pigs, captive monkeys, dogs, cats, cattle, and psittacine birds.Transmision: Human infections withM. bovis are well documented, but are much less

common than M. tuberculosis. Immunosuppressed individuals, such as those with the

acquired immunodeficiency syndrome (AIDS), are at particular risk. Ingestion

general pathology laboratory 2010-2011

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