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1

General vs systemic path

General pathology- common reactions of cells and tissues to injurious stimuli- BROAD Systemic Pathology- alterations and underlying mechanisms in organs- SPECIFIC DISEASES IN ORGANS

2

Disease

abnormal body process with or without characterisitic signs.

3

Etiology

CAUSE of a disease 2 Major classes: Genetic(intrinisic)- inherited mutations, disease-associated gene variants, polymorphism Acquired(extrinsic)- infectious, nutrional, chemical, physical

4

Pathogenesis

refers to the mechanism of disease developement; sequence of events from INITIAL stimulus to the ultimate expression of the disease in the response of cells or tissues to the etiology-HOW DOES THIS DISEASE HAPPEN?

5

Molecular and morphologic changes

biochemical and structural alterations induced int eh cells and organs of the body; the change may be characterisitc of a disease or diagnostic of an etiologic process

6

Clinical Manifestations

results of genetic, biochemical, and structural changes in cells and tissues; functional abnormalties: -signs(animals)- you as a clinican see -symptoms (humans) what the pt feels and tells you

7

Example of Etiology

canine herpesvirus

8

Diagnosis

concise statement or conclusion concerning the nature, cause, or name of a disease

9

autolysis

self-digestion or degradation of cells and tissues by the hydrolytic enzymes normally present in tissues; occurs after somatic death, which is why you want to collect tissues right after death; important for endocrine tissue, eye, NS tissue, GI tract, pancrease, gall bladder, bone marrow

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Somatic Death

due to total diffuse hypoxia( lack of oxygen); cells degnerate as described for hypoxic cell injury

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Putrefaction/decomposition

process by which post mortem bacteria break down tissues;

this gives different color, texture changes, gas production, odors

12

Morphologic appearance of postmortem changes

changes vary depending on: cause of death, environment and body temp, and microbial flora

13

Cool environments inhibits

autolysis; EXCEPTIONS: ruminants forestomach and the equine cecum and ascending colon

 

 

14

Will ingesta continue to undergo bacterial fermentaion post-mortem?

YES due to gas and eat

15

Livor mortis

which ever side you die on; the blood will be more constricted toward that area;

variation in color of tissues such as skin, lung, kidney, and liver

in some areas the tissues will be more red and in other areas pale due to that the blood was kept away----- you can get impressions on other organs, such as intestines on the kidney

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rigor mortis

rigidity- depends on the size of the organism; starts at the head; the muscles become stiff;

 

refers to the contraction of the muscles after death;

begins 1-6 hours post-mortem and continues for 1-2 days

High heat and high activity before death accelerate the onset of this( i.e. race horse collapses after death)

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Algor mortis

the lower of body temperature after death; depends on the environmental temperature and the temperature of the body at the time of death

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postmortem clotting

occurs several hours post death in the heart and vessels; influenced by ante mortem changes in the blood;

Warfarin posioning(rat poision) can also cause this

19

Chicken clot

appearance due to separation of RBC to the bottom and clotted serum at the top; two different colors of the blood clot- a redish and a yellowish color

20

pre vs post mortem clots

Pre- attached to vessel walls( arterial type); loosely attached to vessel walls (venous thrombi, may resembel post mortem clots); dry and duller in color; easy to break post- unattached to vessel walls; shiny and wet, elastic

21

hemoglobin imbibition

red staining of tissue, espesically the heart, arteries, and veins

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Bile imbibition

bile in the gallbladder starts to penetrate the wall and stains the adjacent tissues; yellowish to greenish brown; tissues stained are those in contact with the gall bladder( liver, intestines, diaphragm)

23

Bloating

results from post-mortem bacterial gas formation in the lumen of the GI tract

24

Corneal opacity/clouding

due to dehydration of cornea/due to cold temperatures of the carcass. Most different this from cataracts

25

Pseduomelanosis

refers to the greenish-black discoloration of tissues post mortem(decomposition of blood by bacterial action forming hydrogen sulfide with iron); occurs soon after death, like in the gut, also will be common to see in those tissues in contact with the gut; kidney, liver, spleen, even the gut wall itself

26

Pathology studies:

Structure, biochemical, functional- in repsonse to injurious agents and cells

27

First change in cell injury

biochemical alterations

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4 Aspects of a disease

1. Etiology 2. pathogenesis 3. molecular and morphological changes 4. clinical manifestations

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Molecular and morphological changes

biochemical and structural alterations induced int he cells and organs of the body; the changes MAY BE characterisitic of a disease or diagnostic of an etiological process

30

Clinical manifestations

results of genetic, biochemical, and structural changes in cells and tissues; humans- symptoms; signs in animals

31

Hemorrhage is a/an _______ process

an acute process

32

differental diagnosis

list of diseases that could account for the evidence or lesions of the case; DAMN IT V scheme

33

Main types of pathological processes

1. degeneration/necrosis 2. inflammation/repair 3. tissue deposits/pigementations 4. circulatory disorders 5. disorder of growth (adapation vs neoplasia vs malformations)

34

Etiological Diagnosis

more definitive dx and names the SPECIFIC causes of the disease

35

clinical pathological diagnosis

based on the changes observed in the chemistry of fluids and the hematology

36

Localization

Where is the change?

37


emphysema

accumulation of gas in an organ or tissue;

38

Is freezing an animal for necropsy the same as refrigeration?

NO! If you freeze an animale, the water inside of it will crystalize the tissue; the cells will be destroyed

39

What are some of the early post-mortem changes?

-livor mortis

- rigor mortis

-algor mortis

-corneal clouding

-tache noire

- drying and dark discoloration of the lips

40

Is this normal?

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Yes. This is a normal early post-mortem change called corneal clouding/ opacity.

 

This is due to dehydration of the cornea due to the cold temperature of the carcass.

Can differentiate from cataracts because it is very symetrical and from pt. hx.

41

Carcass Temperature

Can tell us time of time;

you make a hole in the skull; the temperature in the skull linearly decreases;

other sites have other variants: wool, fat;

THIS IS A VERY IMPORTANT STARTING POINT

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Chicken clot

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Post Mortem Clot;

unattached to vessel walls

shiny and wet, perfect cast of vessel lumina

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Pre- mortem clots( mural thrombi and thromboemboli)

attached to vessel walls(arterial type)

loosely attached to vessel walls(venous thrombi- can look like post-mortem clots)

Dry and Duller in color, laminated

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Hemoglobin imbibition

red staining of tissue, especially the heart, arteries, and veins

Hg is released by lysed RBC's and penetrates the vessel wall and extends into the adjacent tissues

this can also occur in acute intravascular hemolysis

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Bile Imbibition

bile in the gallbladder starts to penetrate the wall and stains the adjacent tissues- yellowish to greenish brown

 

Tissues stained are those in contact with the gall bladder- liver, intestines, and see in the picture--- the diaphram

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Pseduomelanosis

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Late Post mortem changes

- bloat

 

- hemoglobin imbibition

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Etiology

the study or theory of the factors that cause disease and the method of their introduction to the host

or

the causes or origin of a disease or disorder

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2 major classes of factors causing disease

1. genetic- inherited mutations and disease associated gene variants

2. acquired- infectious, nutritional, chemical, or physical

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Can only one etiological agent, only cause one disease?

No. One etiological agent can cause mulitple diseases.

52

Most diseases are....

Multifactoral with mulitple factors, etiologies, risk factors can cause disease

i.e. a farm of cattle with GI signs; if you keep introducing more cows to this enviornment, they have an increased risk of getting the disease

 

53

Promotors

something that promotest to neoplasia

i.e. being around chemicals can promote getting lung cancer

54

Examples of a Genetic Diseases


PKD (polycystic kidney disease)
Osteogenesis imperfecta
Spider lamb chondrodyspla

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Cryptococcosis, thalamus,
cerebellum, and mesencephalon,
transverse sections,
cat Cavitational” lesions caused by
Cryptococcus neoformans
 

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What stain do you use for cryptococcus neoformans?

Mayer's mucicarmine stain

57

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Spider lamb chondrodysplasia, spine, longitudinal section, Suffolk lamb

 

THIS IS A GENETIC DISEASE!!!

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One Etiology that is responible for muliple syndromes

Deficiencies in Vitamins

I.e.  Vit D in a puppy- Rickett's Disease

Vit D in an adult- osteomylasia or Ricket's of adults

 

Vit. E- important antioxidant

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Hepatosis dietetica (nutritional hepatic necrosis) Deficiency of Vitamin E and/or Selenium

 

species: pig

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Gastric ulcer (pars esophagea), stomach, pig

growing pigs

stratified squamous epithelium surrounding the cardia (pars esophagea

Causes include:

-  ingestion of finely ground grain or pelleted feed (possibly deficient in vitamin E)

-  fermentation of sugars in the feed

-  stress of confinement rearing- lot of movement of the pigs

THIS IS A DISEASE OF DOSEMTIC PIGS

 

 

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ARDS /shock lung

acute/adult respiratory distress syndrome) in humans

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Autoimmune Diseases

 Multi-factoral;

I.e. systemic lupus erythematosus(SLE) type III hypersensitivity

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Bovine respiratory disease (BRD) complex

This could be any of these listed:

Pneumonic mannheirniosis (Mannheimia haemolytica)  Respiratory histophilosis (Histophilus somni)
 Infectious bovine rhinotracheitis virus (IBR/BHV-1)
 Parainfluenza-3 (PI-3 virus)

 Bovine respiratory syncytial virus (BRSV)

 

Thus, there are muliple explanations for respiratory symptoms in cows.

64

First stage/agent of Bovine enzootic pneuomonia

- not that bad on their own- virsuses

but if they hurt the membranes then 2nd stage opportunisitc pathogens get through and they can do real damage

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Major types of Pathological Processes

1. degeneration/necrosis

2. inflammation/repair

3 tissue deposits/pigmentations

4. circulatory disorders

5. disorders of growth (adapation vs neoplasia vs malformation)

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What kind of a pathological process is this an example of?

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Adaptation, degeneration, and cell death

Squamous metaplasia, esophagus, parrot

this will decrease the secretion

 

Avitaminosis

 

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What pathological process is this an example of?

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Inflammation and Repair

Embolic(comes through the blood) nephritis, kidney, horse

white, yellowish nodules

bacterial lodge and there is an inflammatory response

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What is this in terms of pathological process?

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Tissue deposits and pigementations

 

Defect in heme synthesis caused by a deficiency in uroporphyrinogen III cosynthetase

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This is an example of which pathological process?

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Circulatory disorders

Chronic passive congestion (nutmeg liver), liver, cow- defect in right heart;

Right sided heart failure
Ingestion of hepatotoxin (i.e. Wedelia glauca etc)

the blood can't advance toward the heart

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This is an example of a _____ disorder

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Genetic disorder

Not enough myelin

Globoid cell leukodystrophy, dog (a type of Lysosomal storage disease)

 

you get GOBLOID cells

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This is an example of _______

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Diseases of immunity

Bovine, Nasal epithelium MDx: Acute allergic rhinitis with secondary plant foreign body

Type I hypersensitivity reaction – plant allergen- MAST CELLS released and eosinophils react

to this plant

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What type of pathological process is this?

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Neoplasia or Infectious Disease

 

Bovine abomasal lymphoma

Bovine Leukemia Virus

 

GALTS- are where the lymphoma comes from

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What type of pathological process is this?

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Microbial Infections

Epithelial plaques, papular stomatitis,

hard palate mucosa, calf

Parapoxvirus

 

multi-focal lesion

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What pathological process is present

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Adapation, degeneration, and cell death

 

Prostatic hyperplasia(benign prostatic hyperplasia), Dog

 

This will cause a lot of clinical signs.

Multi-step process- can go into prostatic carcinoma

75

Cell adaptation

Occurs when the cell homeostasis distorted by stresses or pathologic stimuli

Ways that it can adapt:

-atrophy

-hypertrophy

-hyperplasia

-metaplasia

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Homeostasis

tendency to stability in the normal body states of the organism; it is the ability to maintain internal equilibrium by adjusting its physiological processes

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Atrophy

Decrease in size and/or number of the cells and their metabolic activity after normal growth has been reached

 cells are not dead

THEY STILL WORK

↓ protein synthesis and ↑protein degradation in cells

Causes:
 ↓ workload
 denervation
 ↓ blood supply or oxygen

  inadequate nutrition
 loss of endocrine stimulation

aging

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Examples of Atrophy

Muscle disuse in a limb that is in a cast

  Sedentary atrophy

  Atrophy of adrenal cortex by reduction of ACTH stimulation (steroid therapy)

  Atrophy in tissues adjacent to a tumor due to pressure and compromised blood supply

  Physiologic atrophy (eg: non-lactating mammary gland)

 

-larynegeal atrophy- "Roaring"

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This is an example of ....

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cellular atrophy

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What is this an example of?

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Serous atrophy of fat- shiny fat; dilated lymphatics- loss of fat due to poor nutrition

Can also occur in the bone marrow- j

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Hydrocephalus with compression atrophy, cat

 

severe compression of the brain

and hydrocephalus(fluid accumulation in the brain)

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Hypertrophy

Increased size of cells and their functions Synthesis of more organelles and structural

proteins: bigger cells

 More common in cells with little replication  stable or permanent cells: cardiomyocytes, neurons

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Example of Hypertrophy

pregnant uterus

weightlifter

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What is common in Main Coon cats?

Hypertrophic cardiomyopathy (HCM) in cats

Mutation in MYBPC3 gene

Inherited autosomal dominant

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Hyperplasia

 Increase in the number of cells of an organ

 Cells capable of replication

 

Can occur with hyperplasia

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Examples of Hyperplasia

Hormonal: e.g.: breast during pregnancy

Compensatory: e.g.: hepatectomy

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1st and 2nd stage of hypertrophy

1st stage- concentric

2nd stage- eccentric (thicker)

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Hyperplasia
- most commonly caused by excessive hormonal or growth factor stimulation

Epidermal thickening- starts in the basal layer

(repeated irritation)

SCC Epidermal hyperplasia proceeds to dysplasia, carcinoma in situ and invasive squamous cell carc

can also happen with respiratory mucosa

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Fibrous hyperplasia (formerly part of fibrous or fibromatous epulis, gingival hypertrophy)

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Metaplasia

 Change in phenotype of a differentiated cell

  Response to chronic irritation

 cell withstand stress

  May result in ↓ functions or ↑ propensity for malignant transformation (neoplasia)

  Reversible if cause is removed

  Most often in epithelial cells

 

HISTOLOGICAL DX

91

Examples of Metaplasia

 Chronic irritation in lungs

 Vit-A deficiency
 Estrogen toxicity
 In mammary tumors

in urinary tract

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Dysplasia

Refers to abnormal development

 Mostly of epithelial cells

 Term mostly used in

neoplastic processes

 Near-synonym: “Carcinoma in situ”

HISTOLOGICAL ONLY

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Describe

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Atrophy

urolith, which caused compression atrophy

Kidney- Nephrolith

(xanthuinuria) with hydronephrosis, cortical and medullary atrophy and medullary fibrosis diffuse

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Describe

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Hyperplasia to neoplastic from left to right

sqamous cell caricoma

95

Describe

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stomach diffuse marked with chronic gasic HYPERTROPHY

E: cryptosproidiym serpentis

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Esophagus and stomach

gastric lymphoid HYPERPLASIA, multifocal

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Liver, hepatocellular carcinoma with nodular hyperplasia

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Kidney-hydronephrosis with secondary severe diffuse cortical ATROPHY

 

also ureter- hydroureter

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cytosol

fluid within the cell;

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THE GENOME: DNA ORGANIZATION

Organization of DNA.

DNA is organized in an antiparallel configuration: 5′ to 3′ and 3’ to 5’

A purine is bound to a pyrimidine by hydrogen bonds:

A:T and G:C

o Purines = adenine (A), guanine (G)
o Pyrimidines = cytosine (C), thymine (T)

• The helix occurs naturally because of the bonds in the phosphate backbone.

101

Chromatin organization.

DNA is organized around histones into nucleosomes. Nucleosomes are wound into a helix to form chromatin. Chromatin wound again into a supercoiled chromosomes.

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membrane-bound organelles allows for

Isolation of potentially harmful substances

o e.g. degradative enzymes, reactive metabolites

2) Creation of unique intracellular microenvironments o e.g. low pH, high Ca2+ concentrations

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Nucleus

Storage of genetic material
• DNA complex to protein = chromatin

o Euchromatin – uncoiled, transcriptionally active(light)
o Heterochromatin – coiled, transcriptionally inactive(dark
)

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Nucleolus

Organelle of the nucleus

Composed of: RNA, protein, chromatin

Functions in synthesis of rRNA

Prominence is a subjective measure of a cell’s synthetic activity

 

Look like pale white dots

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BIOSYNTHESIS organelles

Nucleus

Endoplasmic reticulum (ER)

Smooth ER (SER)

Golgi apparatus

Endosomal vesicles

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Rough ER (RER)

Contains ribosomes

‒  Site of protein synthesis (esp EC)

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Smooth ER (SER)

Lacks ribosomes

‒  Locus of enzymes that metabolize steroids, drugs, lipids, and glycogen

108

Golgi apparatus

Synthesis of complex proteins
o Production of secretory vesicles and

lysosomes

109

Endosomal vesicles

Shuttles internalized material w/in cell

o Directs newly synthesized materials to cell surface or cell organelle

110

WASTE MANAGEMENT

Lysosomes
‒ Digest macromolecules

o Proteasomes

‒  Selectively degrades denatured

proteins

‒  Release peptides

o Peroxisomes
‒ Breakdown fatty acids
‒ Generates hydrogen peroxide

111

Cell Polarity

Refers to the spatial differences in shape, structure, and function of cells

‒ Epithelial cells:
o Apical surface (top of the cell)
o Basilar surface (bottom of the cell)

 Exposed to different environments  Have different functions

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Cytoskeleton

Contents and position of cell organelles are regulated by the cytoskeleton.- cell polarity

Cytoskeleton

‒  Responsible for cell movement

‒  Maintains cell shape and intracellular organization

‒  Can move organelles and proteins within the cell

113

Components of the cytoskeleton:

Actin microfilaments- biggest- cell structure
• Intermediate filaments -support cell; different proteins to tag to tell us what kind of cell it is

• Microtubules- smallest- where signalling occurs

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CELL MEMBRANES

2 Main functions
1) Selective barrier

2) Structural base for enzymes and receptors

115

Functions of Membrane Proteins

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MITOCHONDRIA

Evolved from ancestral prokaryotes engulfed by eukaryotes

Contain their own DNA

Maternal inheritance

Function:

1) Site of aerobic metabolism- Kreb's cycle

2) Regulator of apoptosis

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Which part of the nucleus is not being actively transcribed?

A. Heterochromatin

B. Euchromatin
C. Histones
D. Nucleolus

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A. Heterochromatin

118

Spatial differences within cells is referred to as:

A. Cell structure

B. Cell polarity
C. Cell metabolism

D. Cell function

Cell Polarity

119

Cell Injury

Damage or pathologic alterations in molecules and/or structure that can occur in cells and extracellular components.

120

DAMNITV

D Degenerative

A Autoimmune

M  Metabolic

N  Neoplasia, Nutritional

I Inflammatory, Infectious, Iatrogenic, Idiopathic T Trauma/ Toxins
V Vascular

Degenerative changes are a mechanism, not an etiology

121

Extrinsic causes

Physical trauma

‒  Viruses

‒  Toxins

122

Intrinsic

Genetic mutations

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CAUSES OF CELL INJURY

Variable response by cells to stressors and stimuli

‒  Maintain homeostasis

‒  Protective mechanisms
 Cell injury occurs when the cell cannot maintain a steady state

124

CAUSES OF CELL INJURY: OXYGEN DEFICIENCY

O2 required for cellular respiration: oxidative phosphorylation in the mitochondria

Hypoxia • partial reduction in O2 delivery to a tissue

‒  Inadequate oxygenation of blood

‒  Reduced transport of O2 in blood

‒  Reduction in blood supply = ischemia

‒  Blockage of cell respiratory enzymes- cynaide blocks electron transport chain

Anoxia • no O2 delivery to a tissue

125

CAUSES OF CELL INJURY: PHYSICAL AGENTS

 Trauma
 Temperature extremes

 Electrical injury
 Ionizing Radiation

126

CAUSES OF CELL INJURY: INFECTIOUS AGENTS

Viruses

‒  Obligate intracellular parasites; use host cell enzyme systems

‒  Cell survival depends on method viruses leave the cell

  Bacteria ‒ Toxins

‒ Overwhelming and uncontrolled replication

 Fungal (mycosis)

‒ Progressive, chronic inflammatory disease

 Protozoan

‒ Replicate in specific host cells

cell destruction

 Metazoan parasites
‒ Inflammation, tissue distortion, utilization of host nutrients

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CAUSES OF CELL INJURY: IMMUNE DYSFUNCTION

Immune system fails to respond to infectious agents

 Congenital defects: SCIDS (Arabian foals)- don't mount proper immune response

 Acquired defects

‒  May be transient (but not always)

‒  Results from damage to lymphoid tissue

• Viral infections

• Chemicals
• Drugs

 Autoimmune diseases
 Hypersensitivity reactions

128

MECHANISMS OF CELL INJURY: 6 MAJOR MECHANISMS

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MECHANISMS OF CELL INJURY: DEPLETION OF ATP

ATP

• Produced through 2 primary metabolic pathways 1. Aerobic: The TCA cycle (Kreb’s cycle)
2. Anaerobic: Glycolysis

• Both require glucose

• ATP is required for almost all synthetic and degradative processes within the cell

Depletion of ATP

Associated with:
1) Hypoxic injury

2) Toxic injury

e.g. cyanide

Fundamental cause of necrotic cell death.

 

130

What  3 things happens when ATP is delplected?

Depletion of 5% to 10% = BAD

1. Na+/K+ ATPase pump failure

o Cell swelling
o ER swelling
o Plasma membrane damage

2. Altered cell metabolism

o Anaerobic glycolysis:

‒ Depletion of glycogen stores

‒ Increased lactic acid↓pH

loss of enzyme function

3.Ribosome detachment

o Decreased protein synthesis

 

Culminates in irreversible mitochondrial and lysosomal membrane damage END STAGE NECROSIS

131

MECHANISMS OF CELL INJURY: MITOCHONDRIAL DAMAGE

3 major consequences

1. Formation of the mitochondrial permeability transition pore (MPTP)

- in the walls of the mitochondria

-apopostis also stimulates this

-pore leaks contents of the mitochrondia into the cytoplasm

CYTOCHROME C- drives apopostis

- disrupt electrochemical potential- stops ATP production

2. Production of ROS

3. Activation of apoptotic pathways

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MECHANISMS OF CELL INJURY: LOSS OF CALCIUM HOMEOSTASIS

Accumulation of Ca2+--- can also drive apopsotis

• Opening of MPTP

 ↓ ATP

• Enzyme activation

‒ Phospholipases

‒ Proteases
‒ Endonucleases

‒ ATPases

• Activation of caspases induction of apoptosis

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MECHANISMS OF CELL INJURY: ACCUMULATION OF REACTIVE OXYGEN-DERIVED FREE-RADICALS

Free radicals
• Chemicals with a single unpaired electron in an outer orbit

Mechanism:

1)  Unstable configuration

2)  Interacts with adjacent molecules: proteins, lipids, carbohydrates, nucleic acids, etc.

3)  Initiates autocatalytic reactions

 

134

Removal of Free Radicals

Removal of Free Radicals
o Spontaneous decay: O2* + H2OO2 + H2O2

o Antioxidants: Vitamin E, Vitamin A, glutathione ‒ Block initiation
‒ Inactivate (scavenge)

Removal of Free Radicals

o Storage and transport proteins: transferrin, ferritin, ceruloplasmin ‒ Bind reactive metals: Fe, Cu

Removal of Free Radicals

o Enzymes: catalase, superoxide dismutase, glutathione peroxidase ‒ Break down H2O2 and O2*
‒ Located near sites where oxidants are formed(mitochondria ie)

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Production of Free Radicals

Production:

‒  During mitochondrial respiration

‒  Absorption of radiant energy

‒  Inflammation

‒  Enzymatic metabolism of drugs or toxins

‒  Transition metals (Fe, Cu)

o Degraded and removed by cell defense systems

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When free radicals are low,

cells maintain a steady-state

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Oxidative Stress

ROS production exceeds antioxidant capacity(Typical of aging)

‒ Cell injury
‒ Cancer
‒ Aging
‒ Degenerative disease

o Classic example: INFLAMMATION

‒  Neutrophils (Nɸ) and macrophages (Mɸ)

‒  Mediators for destroying microbes, dead tissue, etc.

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Pathologic effects of free radicals

Lipid peroxidation in membranes

‒  MOA: Forms peroxidesautocatalytic reaction (propagation)

‒  Extensive membrane damage

o Oxidative modification of proteins

‒  MOA: Oxidation of amino acid side chains,

Formation of protein cross-linkages (e.g. disulfide bonds),

Oxidation of protein backbone

‒  Damage active sites, change conformation, enhance degradation

o Lesions in DNA

‒  MOA: Single or double stranded breaks,

Cross-linking of DNA strands,

Formation of adducts

‒  Cell aging, malignant transformation

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MECHANISMS OF CELL INJURY: MEMBRANE DAMAGE

Mechanism of membrane damage
o Reactive oxygen species
o Decreased phospholipid synthesis

o Increased phospholipid breakdown

o Cytoskeletal abnormalities
‒ Activation of proteasesdamaged cytoskeleton ‒ Cellsstretchandrupture

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Consequences of membrane damage

Mitochondrial membrane damage

‒ Opening of the MPTP↓ATP

‒ Release of pro-apoptotic proteins o Plasma membrane damage

‒  Loss of osmotic balanceinflux of fluids and ions

‒  Loss of cell contents and metabolites

o Injury to lysosomal membranes

‒  Leakage of enzymes into the cytoplasm:

RNases, DNases, proteases, phosphatases, glucosidases

‒  Enzymatic digestion of RNA, DNA, proteins, etc.

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MECHANISMS OF CELL INJURY: DAMAGE TO PROTEINS AND DNA

Protein damage
o Cells have repair mechanisms for misfolded proteins o When overwhelmedinitiates apoptosis

• DNA damage
o Cells have repair mechanisms
o When overwhelmedinitiates apoptosis

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Inflammation

Definition:Reaction of vascularized living tissues to injury.

• Characteristics:
– Involves changes in vascular bed(endothelium, connective tissue etc), blood,

connective tissue

– Intended to eliminate irritant and repair damaged tissue

It WILL END WITH REPAIR!

Itoccursonlyinliving tissue

• Is a response and as such it requires an initiating stimulus (etiology)

 

143

Signs of inflammation

- Redness

• Heat
• Swelling

• Pain

• Loss of function

144

Roles of inflammation

• Dilute, contain and isolate injury(i.e. abscess)
• Destroy invading microorganisms and/or

inactivate toxins
• Achieve healing and repair

145

Outcomes of inflammation

A. Ideal conditions‐ return to normal

B. Intense inflammatory response‐ attempt to separate injured tissue

C. Failure to eliminate insult‐ sequel

146

If immflammation returns to normal

– Elimination of the source of injury

– Resolution of inflammatory process

– Restoration of normal tissue architecture and physiologic functions

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Intense inflammatory-  Outcomes of inflammation (cont.)

response:

Attempt to isolate inflammatory process, formation of a wall (such as a capsule in an abscess)

 

 

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Failure to eliminate insult‐ sequel

Persistence of inflammatory cells

Chronic dermatitis (ventral view, midline) in a cow. Etiologic diagnosis: Parasitic dermatitis
Source: Dr King’s Show and tell web site.

– Scar formation

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Is Inflammation always a good thing?

It can be more harmful than the initiating stimulus

• Inflammation is fairly stereotyped/predictable irrespective of the initiating stimulus- whatever the stimulus is, the process of inflammation is basically the same

150

Inflammation is critically tied to the

It is critically tied to the blood (plasma, circulating cells, blood vessels, cellular and extracellular components of connective tissue).

• It is highly redundant with many promoters and regulators

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Inflammation ends when....

when the stimulus is eliminated

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Inflammation is closely assoicated with the process of ____

repair. Repair begins during inflammation and it is completed when injurious stimuli have been neutralized.

Damaged tissue is replaced commonly by combination of both regeneration by native parenchyml cells and filling of the defeat with fibrous tissue (scarring)

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Exudation

escape of fluid, proteins and blood cells from the vascular system into the interstitium or body cavities. Exudation implies alteration of the normal permeability of local blood vessels

154

Exudate

Inflammatory extravascular fluid that has:

– a high protein concentration

– much cellular debris
– specific gravity above 1.020

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Transudate

essentially an ultra filtrate of blood plasma and results from hydrostatic imbalances across the vascular endothelium. A transudate is a fluid with:

– low protein content
– specific gravity of less than 1.020

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Exudate

Pyothorax in a cat

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Transudate

Hydrothorax in a sheep

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Edema

denotesan excess of fluid in the interstitial tissue or serous cavities, it can be an exudate (inflammatory edema) or a transudate( due to changes in hydrostatic pressure)

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Pus

An inflammatory exudate rich in leucocytes (primarily viable and degenerated neutrophils) and parenchymal cell debris

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serous

watery

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fibrinious

fibrin is the main component

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suppurative

pus

163

granulomatous

chronic, with lots of macrophages

164

Clinically can you see the difference between minimal and mild?

No, only histologically

165

peracute

suddenly

166

chronic active

chronic condition that is still going on

i.e. pancreatitis

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This is a case of exudative dermatitis in a pig. Name of the disease: Greasy pig disease

 

Severe

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peracute

Usually caused by a potent stimulus
• Usually the animal has no time to respond

• Less common than acute disease processes

i.e. bee sting

 

GENERAL FEATURES:

• TIME: 0‐4 hours

• VASCULARI NVOLVEMENT:

– Hyperemia

– Slight edema

– Hemorrhage

• INFLAMMATORY CELLS:

– Not usually numerous
– Few leucocytes

• CLINICALSIGNS:Shock,suddendeath

 

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Peracute inflammation

Infectious canine Hepatitis

 

In picture: Intranuclear inclusions within glomeruli

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Acute Inflammation

TIME: It begins within 4‐6 hours

• VASCULAR INVOLVEMENT:

• Active hyperemia
• Edema (due to endothelial damage‐lymphatics and

small blood vessels)
• Occasional fibrin thrombi within vessels

INFLAMMATORY CELLS: In acute inflammation, leucocyte infiltration is variable (dependent upon TIME), in general neutrophils usually predominate, but sometimes mononuclear cells (lymphocytes and plasma cells) can also be present.

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Acute inflammation: migration of neutrophils

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Clinical signs of Acute Inflammation

CLINICAL SIGNS: Most of the following classical clinical signs are associated to vascular changes:

– Warm: Calor
– Reddened: Rubor
– Swollen: Tumor
– Painful: Dolor
– Loss of function: Functio laeso

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Role of Lymphatics in Acute Inflammation

LYMPHATICS: Lymphatic vessels have a role in moving away the exudate. The transportation of the exudate (i.e., inflammatory cells and necrotic debris) can lead to acute regional lymphadenitis.

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Lymphadenitis(inflammation of the lymphnodes): reactive inflammation of lymph node(s) occurs in acute, subacute and chronic inflammation

Chronic inflammation of mesenteric lymph nodes in a Llama, due to tuberculosis

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Lymphangitis= inflammation of lymphatic vessel(s)

Thickening of serosal lymphatic vessels (chronic lymphangitis), due to Johne’s disease. Goat small intestine.

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SUBACUTE INFLAMMATION

Subacute is defined as a gradual change, between acute and chronic.

• This term is used when the inflammatory response does not include reparative responses such as fibroplasia and angiogenesis.

TIME: Depending on the nature of the inciting stimulus, it may cover a considerable time span which can vary from a few days to a few weeks.

VASCULAR INVOLVEMENT: There is a decline in the magnitude of vascular changes, compared to acute inflammation (less hemorrhage, hyperemia and edema).

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Inflammtory cells in Subacute Inflammation

INFLAMMATORY CELLS: Subacute inflammation is characterized by a "mixed" or "pleocellular" inflammatory infiltrate. This means that the inflammatory cell type still may be primarily neutrophilic but usually it is also associated with an infiltration by lymphocytes, macrophages and plasma cells.

• •

Fibrosis and neovascularization are not features of subacute inflammation.

SUBACUTE INFLAMMATION

LYMPHATICS:
– Increased lymphatic drainage – Repair of endothelial damage

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subacute stomatitis in a bovine

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CHRONIC INFLAMMATION

The inflammatory response usually is accompanied by an immune response.

CHRONIC INFLAMMATION

FEATURES OF CHRONICITY:

MACROPHAGES

Chronic inflammation is often the result of a persistent inflammatory stimulus in which the host has failed to completely eliminate the causative agent.

Chronic inflammation is characterized by evidence of host tissue response in terms of repair:

– Scar formation: fibrosis
– Parenchymal regeneration

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Origin of chronic inflammation

It may follow an acute inflammatory phase.

– It may develop as an insidious, low‐grade, subclinical process without history of a prior acute episode.

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Chronic Inflammation

Inflammation of the bone

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Chronic Inflammation- Vascular

TIME: Variable

• VASCULAR INVOLVEMENT: Chronic inflammation is characterized by proliferation of capillaries and small blood vessels (angiogenesis/ neovascularization) resulting in hemorrhage and congestion.

• HOST INVOLVEMENT: Parenchymal regeneration or repair by fibrosis (scarring).

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Multifocal ulcerative colitis, chronic. Feline

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Inflammatory cells in Chronic Inflammation

INFLAMMATORY CELLS: Primarily Mononuclear Inflammatory Cells

–  Lymphocytes

–  Macrophages: cells responsible for phagocytosis

and tissue debridement in a chronic lesion.

–  Plasma cells

–  Fibroblasts

LYMPHATICS: Lymphatic involvement is variable. Sometimes there is proliferation and activation, or lymphatics may not play a significant role.

• CLINICAL SIGNS: Chronicity is primarily a clinical concept pertaining to prolonged duration of an inflammatory lesion.

NOTE: Many of the changes represented in chronic inflammation are also seen in areas of REPAIR.

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Chronic lymphangitis. Johne’s disease in a goat- white chords

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FOCAL INFLAMMATION

Definition: Single abnormality or inflamed area within a tissue

• Size: Varies from 1 mm to several centimeters in diameter

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Focal lesion in the brain of a deer. Cut surface reveals presence of cloudy, yellowish material (interpreted as pus)

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Focal keratitis in a bovine.

Moderate- severe

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MULTIFOCAL

Definition: Arising from or pertaining to many foci

• Size: Variable. Each focus of inflammation is separated from other inflamed foci by an intervening zone of relatively normal tissue

Mutifocal hepatitis in a peacock.

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LOCALLY EXTENSIVE

Involves a considerable zone of tissue within an inflamed organ.

• Possible origins:

LOCALLY EXTENSIVE

– Severelocalreactionsthat spread into adjacent normal tissue

– Coalescenceoffociina multifocal reaction

• EXAMPLE: Cranioventral aspects of the lungs are involved (dark red) while the dorsal portions are spared

- gangrene is another example

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Locally extensive pneumonia in a pig

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DIFFUSE

Althoughvariationsin severity of the inflammation may occur, the entire tissue is involved. EXAMPLE: Interstitial pneumonia.

• Diffuselesionsareoften viral or toxic in etiology.

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Suppurative Exudate

SYNONYM: Purulent Exudation ‐ consisting of, or containing pus; associated with the formation of pus.

• Pus: a liquid inflammation product composed of: – accumulated dead cells (both tissue cells and

inflammatory cells)

– variable numbers of viable leucocytes (primarily neutrophils)

– fluids added by the inflammatory edema‐forming process.

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Suppurative/ Purulent Exudate

Grey discoloration in cranioventral areas of the lung. SEVERE

FRIABLE- Locally Extensitive

 

Have to look at histologically

Neutrophils within alveolar spaces

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Severe suppurative pyelonephritis in a dog

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Pyometra in a dog: a form of severe suppurative inflammation

diffuse

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SUPPURATION

Is the process by which pus (suppurative exudation) is formed. The use of the term suppuration implies that neutrophils and proteolytic enzymes are present, and that necrosis of host tissue cells has occurred.

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ABSCESS

Is a circumscribed (partially walled‐off) collection of pus. Therefore an abscess is a localized form of suppurative inflammation.

• NOTE: Suppurative lesions are often bacterial in origin

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ABSCESS

• GROSS APPEARANCE: is yellow‐white to gray‐ white and varies from watery to viscous depending on fluid content.

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Chronic Suppurative Osteomyelitis

Neutophils came

 

can be called a veretral abyses

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FIBRINOUS EXUDATION

PATHOGENESIS: severe injury to endothelium and basement membranes results in leakage of plasma proteins including fibrinogen, which polymerizes perivascularly as fibrin.

• CONTENTS: Fibrin(pale yellow)

GROSS APPEARANCE: yellow‐white, or pale tan, stringy, shaggy meshwork (or fibrillar material) which gives a rough irregular appearance to the tissue surfaces. Casts of this friable material may form in the lumen of tubular organs.

• TIME: Acute process, it can form in seconds

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What is the first step to adhension?

Fibrin

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FIBRINOUS ENTERITIS

FORMS A PSUEDO LUMEN

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FIBRINOUS EXUDATE

the surface of the mucosa

SEVERE!

Diffuse

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Fibrinous cholecystitis

 

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Fibrinopurulent exudate

This term is used to classify an inflammatory process in which neutrophils and fibrin are abundant

Fibrinopurulent pericarditis in a foal

Have to see histologically to make a final dx

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DIFFUSE SEVERE FIBRINOSUPPURATIVE PERICARDITIS‐ PORCINE

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Fibrinous exudation VS fibrosis

Presence of a fibrinous exudate involves an acute process. In contrast, fibrosis is a chronic process.

• Fibrinontissuesurfacescanbeeasilybroken down. Microscopically, fibrin is composed of thread‐like eosinophilic meshwork that sometimes forms masses of solid amorphous material.

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Fibrinous pleuritis in a horse- Severe, diffuse

Pleural surface covered by friable material

Homogeneous, eosinophilic material . Bacterial colonies (arrows) are basophilic with HE stain

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Fibrinous versus fibrosis: Part of the same process, different stages

Fibrin provides the support for the eventual ingrowth of fibroblasts and neocapillaries, The transformation of the fibrinous exudate (acute process) into well‐vascularized connective tissue (chronic process, is known as organization of the exudate.

• Fibrin is often removed by enzymatic fibrinolysis or by phagocytosis by macrophages before organization can occur.

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Fibrinous inflammation

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fibrous connective tissue adhesions

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Equine heart.
Epicardial surface covered by fibrin Fibrinous pericarditis

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Bovine liver
Cut surface demonstrating thickenning of bile ducts Chronic fibrosing cholangitis

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serOUS EXUDATION

DEFINITION: Inflammatory process in which the exudate occurs in tissues in the absence of a prominent cellular response. May be a dominant pattern of exudation for a wide variety of mild injuries. Example: Traumatic blisters, sunburn, running nose

• CONTENTS: Outpouring of fluid relatively rich in protein, and derived from blood and locally injured cells.

GROSS APPEARANCE:

• Yellow, straw‐like colour, fluid commonly seen in very early stages of many kinds of inflammatory responses

• Ulceration will follow the rupture of a vesicle.

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Serous exudate- can tell from seperation of the membrane

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GRANULOMATOUS INFLAMMATION

TIME: always chronic

• DEFINITION: Granulomatous refers to an inflammatory response characterized by the presence of lymphocytes, macrophages, and plasma cells with the predominant cell being the macrophage.

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Granuloma

Macrophages are clustered in a characteristic elliptical formation around the causative etiologic agent, or around a central necrotic area, or simply as organized nodules.

• Large cells with abundant cytoplasm, referred to as "epithelioid cells, and "multinucleated giant cells" are also commonly present in this type of inflammatory response.

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Diffuse granulomatous inflammation

 

“cerebroid” appearance of affected intestine

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Granulomatous Inflammation

ETIOLOGY: usually some non‐digestible organism or particle which serves as a chronic inflammatory stimulus, delayed‐type hypersensitivity is often required.

– ORGANISMS:
• Mycobacterium, Actinomyces, Blastomyces,

Coccidioides, etc)

– Noninfectious AGENTS: Mineral oil, Complex polysaccharides, Foreign bodies

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Other types of inflammation

Modifierssuchasnecrotizing,hemorrhagic,mucoid can be used in a morphologic diagnosis.

• Basedonthehistologicalcharacteristicsmodifiers could include terms such as eosinophilic, lymphocytic, lymphoplasmacytic and non‐ suppurative.

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Necrotizing Inflammation

Necrosis is the main feature and exudation is minimal. In general, the process is interpreted as inflammatory (rather than purely ischemic) if an infectious etiology is suspected.

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Hemmorrhagic inflammation

Hemorrhage is the main feature of this type of inflammation. The presence of an etiologic agent will indicate that the process is inflammatory rather than a primary circulatory disturbance.

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SEGMENTAL HEMORRHAGIC

ACUTE OR CHRONIC? Acute- no fribrosis

ENTERITIS

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segemental hemorrhagic enteritis

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Diffuse severe hemorrhagic cystitis

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Mucoid enteritis

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MUCOPURULENT OR CATARRHAL

heinflammatory exudate is composed of mucus and pus (neutrophils and cell debris).

 

Bovine‐ Catarrhal rhinitis

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Polymorphonuclear Leukocytes

Neutrophils

– Eosinophils
– Basophils and Mast cells

230

Mononuclear cells

Lymphocytes and plasma cells. – Monocytes and Macrophages – Platelets

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Cell on the left= Polymorphonuclear Leukocytes

Right= lymphocyte

232

LEUCOCYTES/LEUKOCYTES

Leukocytes are normal inhabitants of the circulating blood (except plasma cells, and mast cells).

• •

Each cell type plays a fairly distinctive role

LEUCOCYTES/LEUKOCYTES

The total leukocyte count in peripheral blood and the relative proportions of the different white blood cells may be greatly modified in systemic responses to inflammation.

Each cell type enters into the inflammatory response in a definite sequence.

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NEUTROPHILS

Neutrophils are crucial to the entire inflammatory process.

• Neutrophils constitute the first line of cellular defence (they usually are the first to gather at sites of acute inflammation).

• They develop in the bone marrow and the maturation process takes about two weeks

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The purpose of Neutrophils is to eliminate:

microorganisms

– tumourcells
– foreignmaterial

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Neutrophils are characterized by:

High motility due to rapid amoeboid movement.

– Responsetoawidevarietyof chemotaxtic compounds.

– Phagocyticandbactericidal activities: neutrophils are the major cellular defence system against bacteria.

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Morphology of Neutrophils

Measure 10‐12 μm in diameter with a multilobed nucleus.

• Contain abundant cytoplasmic granules.

• Two major classes of granules have been identified:
– AzurophilGranules:orprimarygranules.Theyarelarge,ovaland

electron dense.

– SpecificGranules:orsecondarygranules.Theyaresmaller,lessdense and more numerous.

• Note: Neutrophils of rabbits, guinea pigs, rats, reptiles, fish and birds have eosinophilic granules, and are called heterophils.

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Neutrophils, fluid and fibrin within the alveolar spaces

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Neutrophils within a bronchi

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neutrophils in blood

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NEUTROPHILS IN TISSUES Suppurative exudate

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NEUTROPHILS: FUNCTIONS

The main functions of neutrophils include phagocytosis and secretion of pro‐inflammatory substances. The purpose of phagocytosis is to ingest, neutralize, and, whenever possible, destroy the ingested particle.

Neutrophils are capable of killing microorganisms by: – producingoxygenfreeradicals
– hydrogenperoxide
– lysosomal enzymes

• •

Neutrophils mediate tissue injury via release of oxygen free radicals and lysosomal enzymes.

NEUTROPHILS: FUNCTIONS

They regulate inflammatory response via releasing chemical mediators such as leukotrienes and platelet activating factor.

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Suppurative endometritis‐ cow

Severe, diffuse

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EOSINOPHILS

Eosinophils are abundant at sites of inflammation in diseases of immunologic, parasitic or allergic origin.

• Eosinophils have unique functions as effector cells for killing helminths and their propensity for both causing and assisting in the regulation of tissue damage in hypersensitivity.

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eosinophiles

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eosinophils morphology

Eosinophils are similar in shape and nuclear morphology to neutrophils, but are slightly larger than the latter cells.

• They can also be distinguished fromneutrophils by the affinity of their coarse cytoplasmic granules for the acid dye eosin.

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EOSINOPHILIC BRONCHITIS

247

Granules in Eosinophils

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Small granules

• Primary granules

• Large secondary (specific) granules:

– Major basic protein- for parasites

– Eosinophilic cationic protein
– Eosinophil‐derived neurotoxin

– Eosinophil peroxidase

Seeaprimarygranule (arrow) and multiple specific granules (*)

248

Major basic protein

Major basic protein is strongly toxic to parasites as well as other kinds of cells. Even rather low concentrations of eosinophil major basic protein can mimic the destructive effects of intact eosinophils on the helminths. Additionally, major basic protein can cause histamine release form mast cells and basophils, as well as neutralize heparin.

249

Eosinophilic cationic

Eosinophiliccationicproteincontributesto parasite killing and also shortens coagulation time and alters fibrinolysis.

250

Eosinophils are also effective in killing

Eosinophils are also effective in killing helminth parasites by antibody‐dependent cell‐mediated cytotoxity.

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Eosinophiles in blood

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Functions of Eosinophils

Modulate hypersensitivity reactions ‐ especially Immediate type

• Defence against helminthic infestations

• Phagocytic but less active phagocytes than neutrophils

253

EXAMPLES OF EOSINOPHILIC INFILTRATION

Allergiessuchas contact dermatitis

• Habronemainfectionin horses.

• Eosinophilsarealso prominent in mast cell tumours, particularly in dogs.

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LYMPHOCYTES AND PLASMA CELLS

Background:

• Both cell types are principally involved in immune reactions

• The key cellular mediators of both the immediate antibody response and the delayed cellular hypersensitivity response.

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monocytes/macrophages

Macrophages are derived from circulating blood monocyte of bone marrow origin.

• A smaller portion may originate from immature resident mononuclear phagocytes in the tissue (also bone marrow origin).

• Monocytes do not have a large reserve pool in the bone marrow, but they remain longer (up to 72 hrs) in the circulation compared to neutrophils.

• Blood monocytes are functional cells but they require activation under the influence of various chemical mediators before they can achieve their maximal functional competence as macrophages.

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Difference between a monocyte and a macrophage

Once monocytes migrate into tissues they are referred to as macrophage.

 

Macrophages in tissues differ from monocytes by being larger and by having a variable number of azurophilic granules and remnants of ingested material.

257

MACROPHAGES

Macrophages have the potential of being activated, a process that results in:

– an increase in cell size
– increased levels of lysosomal enzymes – Increased metabolism

– greater ability to phagocytose and kill ingested microbes.

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Biology of Macrophages

Macrophagesarepartofthemononuclear phagocyte system.

• Themononuclearphagocytesystem(MPS) consists of closely related cells of bone marrow origin, including blood monocytes, and tissue macrophages.

• Tissuemacrophagesarediffuselyscatteredinthe connective tissues or clustered in organs such as the liver (Kupffer cells), spleen and lymph nodes (sinus histiocytes), and lungs (alveolar macrophages)

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MACROPHAGES: FUNCTION

PHAGOCYTOSIS: macrophages are the major scavengers in the inflammatory response.

MACROPHAGES: FUNCTION

MODULATION of inflammatory and repair processes.

REGULATION of immune response (important effector cells in certain delayed‐type hypersensitivity responses).

• PRODUCTION of interleukin‐1, (IL‐1)

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ACUTE INFLAMMATION

EVENTS OF ACUTE INFLAMMATION
1. Stimuliforonsetofacuteinflammation
2. Vascular changes
3. Cellular events
4. Termination of acute inflammatory response

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Vascular changes

Major role maximizing movement of cells and plasma proteins from within circulation to site of injury

• Vascular changes are:
– Increased vascular flow (hyperemia) and caliber of

blood vessels

– Increased vascular permeability (capillaries and post‐capillaries)

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Cellular Events

extravasation= delivery of white blood cells to the site of injury

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Leucocyte adhesion deficiency (LAD)

Disease due to leucocyte adhesion’s failure is known as Leucocyte adhesion deficiency (LAD) in BOVINE

• Etiology: Due to type I mutation in Beta‐1 integrins CD18

• Mechanism:neutrophiliawithimpaired transmigration because neutrophils are unable to adhere

• Clinicalsigns:gingivitis,toothloss,ulcersinoral and enteric mucosa, cutaneous ulcers, pneumonia

• Treatment:None

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Chemotaxis

3. Cellular events‐ Chemotaxis

Definiton:Chemotaxis is the process where white blood cells emigrate in tissues towards the site of injury.

• Chemotaxis occurs right after extravasation

• Granulocytes,monocytes‐andinalesserextend lymphocytes‐ respond to chemotactic stimuli at different speed

• Chemotacticagentsare:
– Endogenous: such as chemical mediators (component

of Complement system or lipoxygenase pathways) – Exogenous such as infectious agents

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Cellular events‐ Phagocytosis

Phagocytosis involves the accumulation of white blood cells at the site of injury followed by release of enzymes by neutrophils and macrophages to eliminate injurious agents

• Phagocytosis involves 3 interconnected processes:

– Recognitionandattachmentof the particle to be ingested

– Engulfmentwithsubsequent formation of phagocytic vacuole

– Killingordegradationofthe ingested material

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Termination of the acute inflammatory response

Degradation of mediators of inflammation

• Stop signals are produced once stimulus is gone

• Stopsignalsinclude:
– Switch from pro‐inflammatory leukotrienes to anti‐

inflammatory lipoxins from arachidonic acid

– Liberation of anti‐inflammatory cytokines such as TGF‐ beta from macrophages and other cells.

– Neural impulses resulting in inhibition of TNF production in macrophages

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Severe multifocal to coalescent dermatitis.
Etiology: Turkey pox virus

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Bilateral locally extensive pneumonia

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 Fibrino-nectroizing enteritis. Pig ileum

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DIFFUSE SEVERE FIBRINOUS PLEURITIS

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Acute inflammation may have one of four outcomes:

1. Complete resolution: Resolution is the usual outcome when the injury is mild.

2. Healing by scarring: after substantial tissue destruction, or when the inflammation occurs in tissues that do not regenerate, or when there is abundant fibrin exudation.

3. Abscess formation: which occurs particularly in infections with pyogenic organisms.

4. Progression to chronic inflammation

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OUTCOME 2‐ HEALING BY FORMATION OF SCAR TISSUE

273

Chronic inflammation

Chronic inflammation: is a type of inflammation resulting from injurious persistent stimuli (often weeks or months), which leads to a predominantly proliferative, rather than an exudative, reaction. In most tissues, fibrosis is the hallmark of chronic inflammation.

274

Clinically, chronic inflammation in various organs arises in one of three ways:

1. It may follow acute inflammation, either because of the persistence of the inciting stimulus, or because of some interference in the normal process of healing. For example, infection of the lung by some species of bacteria may begin as an acute inflammation (pneumonia), but persistence of these organisms or their products leads to tissue destruction, a smouldering inflammation, and a chronic lung abscess.

2. Repeated bouts of acute inflammation may also be responsible, with the patient showing successive attacks of fever, pain, and swelling.

3. Chronic inflammation may begin insidiously as a low‐grade smouldering response that does not follow classic symptomatic acute inflammation.

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chronic inflammation is characterized by the following histologic hallmarks:

infiltration by mononuclear cells,principally macrophages, lymphocytes, and plasma cells

• proliferation of fibroblasts and in many instances, small blood vessels,

increasedconnectivetissue(fibrosis)

tissuedestruction

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Granulomatous inflammation

Granulomatous inflammation is a specific type of chronic inflammation characterized by accumulation of modified macrophages: epithelioid cells, and initiated by a variety of infectious and noninfectious agents.

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Granuloma

Granuloma: small, 0.5 to 2‐mm, organized collections of modified macrophages called epithelioid macrophages, usually surrounded by a rim of lymphocytes. Another feature of the granuloma is the presence of Langhan's giant or foreign body‐type cells and presence of fibrous connective tissue.

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Hepatic granulomas in a red tailed hawk. Etiology: Mycobacterium avium sp

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Etiology of chronic Inflammation

Inert particles such as silica, asbestos

– Lipids resistant to metabolism (mineral oil)

– Bacteria resistant to lysosomal degradation (Mycobacterium sp.)

– Systemic fungal agents (Histoplasma sp., Blastomyces sp., Coccidioides sp.)

– Foreign bodies (wood splinters, suture material, hair shafts)

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Multifocal granulomas in the air sacs Etiologic diagnosis: Mycotic Airsacculitis- Aspergillis

 

Granuloma in the lung.
Fungal organisms stain pink with PAS stain

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Granulationtissue

Granulationtissue=HEALING

282

Fibrous

Fibrous= fibrosis= fibrous connective tissue= formed by fibroblasts and collagen= chronic

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Cells Involved in Granulomatous Inflammation

Epithelioid cells(macrophages)
• Multinucleated giant cells

• Lymphocytes

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multinucleated giant cells

Macrophages are the sources of the multinucleated giant cells, which are believed to be formed by the coalescence of single macrophages.

285

epithelioid cell

Another type of macrophage seen in some kinds of chronic inflammation is the epithelioid cell. These are large, pale‐staining macrophages that have an ovoid nucleus and a shape resembling epithelial cells.

Epithelioid cells are specialized macrophages with the following features:

–  15‐30 micron in diameter

–  abundant lightly eosinophilic, plump cytoplasm

and eccentrically located round to oval nucleus

– rich in endoplasmic reticulum, Golgi apparatus, vesicles and vacuoles.

– specialized for extracellular secretion

– less phagocytic activity than non‐specialized macrophages

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Multinucleated Giant Cells

Multinucleated Giant Cells are formed by coalescence and fusion of epithelioid cells. This fusion is induced by cytokines.

• Multinucleatedgiantcellsmayachievea diameter of 40 to 50 μm and contain over 50 nuclei.

• Nucleiaresometimesarrangedaroundthe periphery (creating a horseshoe pattern: Langhan's giant cells).

• Themultinucleatedcellfunctionissimilartothat of the epithelioid cell.

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T‐lymphocytes

T‐lymphocytes are often present in granulomatous inflammatory reactions. Their roles are:

– to produce lymphokines and interferon
– to attract and activate macrophages
– to induce formation of multinucleated giant cells

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Caseous necrosis, multinucleated giant cells and clusters of lymphocytes

 

close up of a granuloma

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Pattern of chronic Inflammation

Two gross patterns are possible:
– diffuse thickening of affected tissue (eg.: Johne's

disease)
– solid, firm, nodular lesions (eg: Blastomyces

dermatitidis) which may compress adjacent tissue.

• These lesions may contain organized granulomas with necrotic or suppurative centres.

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Histologic features of chronic inflammation

 

• dense accumulations of macrophages, epithelioid cells, giant cells and lymphocytes

• neutrophils and plasma cells are often present

• if significant numbers of neutrophils are present in the centre of a granulomatous reaction, the term pyogranulomatous inflammation is often used.

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pyogranulomatous

if significant numbers of neutrophils are present in the centre of a granulomatous reaction, the term pyogranulomatous inflammation is often used.

292

Simple granuloma

organized accumulation of macrophages and epithelioid cells, often rimmed by lymphocytes.

293

Complex granuloma

granuloma with a central area of necrosis

294

necrosis may lead

– necrosis may lead to calcification / mineralization

295

Morphologic diagnosis

This is a summary of the lesion, but generally does not describe what is causing the lesion: [organ, interpretation, distribution ] (i.e. [small intestine], segmental necrohemorrhagic enteritis).

296

Etiologic diagnosis

This type of diagnosis is restricted to two words only - the causative agent and the site of the lesion (i.e., parvoviral enteritis).

297

Etiology

This is the causative agent only - it may also be stated as cause, causative agent, or etiologic agent. It does not ask for the organ, distribution, or any other type of information (i.e., Canine parvovirus type 2).

298

Neoplasms

name of the neoplasm and the organ in it is located: Renal carcinoma *Certain conditions may be summed up in a single word. Palatoschisis; Cyclopia

299

Pathogenesis

sequence of events from initial stimulus to the ultimate
expression of the disease in the response of cells or tissues
to the etiology (oropharyngeal infectionviremiainfection and death of rapidly dividing cells (enterocytes) from cryptsnecrohemorrhagic enteritis)