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
abnormal body process with or without characterisitic signs.
CAUSE of a disease 2 Major classes: Genetic(intrinisic)- inherited mutations, disease-associated gene variants, polymorphism Acquired(extrinsic)- infectious, nutrional, chemical, physical
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?
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
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
Example of Etiology
concise statement or conclusion concerning the nature, cause, or name of a disease
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
due to total diffuse hypoxia( lack of oxygen); cells degnerate as described for hypoxic cell injury
process by which post mortem bacteria break down tissues;
this gives different color, texture changes, gas production, odors
Morphologic appearance of postmortem changes
changes vary depending on: cause of death, environment and body temp, and microbial flora
Cool environments inhibits
autolysis; EXCEPTIONS: ruminants forestomach and the equine cecum and ascending colon
Will ingesta continue to undergo bacterial fermentaion post-mortem?
YES due to gas and eat
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
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)
the lower of body temperature after death; depends on the environmental temperature and the temperature of the body at the time of death
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
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
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
red staining of tissue, espesically the heart, arteries, and veins
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)
results from post-mortem bacterial gas formation in the lumen of the GI tract
due to dehydration of cornea/due to cold temperatures of the carcass. Most different this from cataracts
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
Structure, biochemical, functional- in repsonse to injurious agents and cells
First change in cell injury
4 Aspects of a disease
1. Etiology 2. pathogenesis 3. molecular and morphological changes 4. clinical manifestations
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
results of genetic, biochemical, and structural changes in cells and tissues; humans- symptoms; signs in animals
Hemorrhage is a/an _______ process
an acute process
list of diseases that could account for the evidence or lesions of the case; DAMN IT V scheme
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)
more definitive dx and names the SPECIFIC causes of the disease
clinical pathological diagnosis
based on the changes observed in the chemistry of fluids and the hematology
Where is the change?
accumulation of gas in an organ or tissue;
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
What are some of the early post-mortem changes?
- rigor mortis
- drying and dark discoloration of the lips
Is this normal?
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.
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
Post Mortem Clot;
unattached to vessel walls
shiny and wet, perfect cast of vessel lumina
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
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
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
Late Post mortem changes
- hemoglobin imbibition
the study or theory of the factors that cause disease and the method of their introduction to the host
the causes or origin of a disease or disorder
2 major classes of factors causing disease
1. genetic- inherited mutations and disease associated gene variants
2. acquired- infectious, nutritional, chemical, or physical
Can only one etiological agent, only cause one disease?
No. One etiological agent can cause mulitple diseases.
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
something that promotest to neoplasia
i.e. being around chemicals can promote getting lung cancer
Examples of a Genetic Diseases
PKD (polycystic kidney disease)
Spider lamb chondrodyspla
cerebellum, and mesencephalon,
cat Cavitational” lesions caused by
What stain do you use for cryptococcus neoformans?
Mayer's mucicarmine stain
Spider lamb chondrodysplasia, spine, longitudinal section, Suffolk lamb
THIS IS A GENETIC DISEASE!!!
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
Hepatosis dietetica (nutritional hepatic necrosis) Deficiency of Vitamin E and/or Selenium
Gastric ulcer (pars esophagea), stomach, pig
stratified squamous epithelium surrounding the cardia (pars esophagea
- 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
ARDS /shock lung
acute/adult respiratory distress syndrome) in humans
I.e. systemic lupus erythematosus(SLE) type III hypersensitivity
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.
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
Major types of Pathological Processes
3 tissue deposits/pigmentations
4. circulatory disorders
5. disorders of growth (adapation vs neoplasia vs malformation)
What kind of a pathological process is this an example of?
Adaptation, degeneration, and cell death
Squamous metaplasia, esophagus, parrot
this will decrease the secretion
What pathological process is this an example of?
Inflammation and Repair
Embolic(comes through the blood) nephritis, kidney, horse
white, yellowish nodules
bacterial lodge and there is an inflammatory response
What is this in terms of pathological process?
Tissue deposits and pigementations
Defect in heme synthesis caused by a deficiency in uroporphyrinogen III cosynthetase
This is an example of which pathological process?
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
This is an example of a _____ disorder
Not enough myelin
Globoid cell leukodystrophy, dog (a type of Lysosomal storage disease)
you get GOBLOID cells
This is an example of _______
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
What type of pathological process is this?
Neoplasia or Infectious Disease
Bovine abomasal lymphoma
Bovine Leukemia Virus
GALTS- are where the lymphoma comes from
What type of pathological process is this?
Epithelial plaques, papular stomatitis,
hard palate mucosa, calf
What pathological process is present
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
Occurs when the cell homeostasis distorted by stresses or pathologic stimuli
Ways that it can adapt:
tendency to stability in the normal body states of the organism; it is the ability to maintain internal equilibrium by adjusting its physiological processes
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
↓ blood supply or oxygen
loss of endocrine stimulation
Examples of Atrophy
Muscle disuse in a limb that is in a cast
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"
This is an example of ....
What is this an example of?
Serous atrophy of fat- shiny fat; dilated lymphatics- loss of fat due to poor nutrition
Can also occur in the bone marrow- j
Hydrocephalus with compression atrophy, cat
severe compression of the brain
and hydrocephalus(fluid accumulation in the brain)
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
Example of Hypertrophy
What is common in Main Coon cats?
Hypertrophic cardiomyopathy (HCM) in cats
Mutation in MYBPC3 gene
Inherited autosomal dominant
Increase in the number of cells of an organ
Cells capable of replication
Can occur with hyperplasia
Examples of Hyperplasia
Hormonal: e.g.: breast during pregnancy
Compensatory: e.g.: hepatectomy
1st and 2nd stage of hypertrophy
1st stage- concentric
2nd stage- eccentric (thicker)
- most commonly caused by excessive hormonal or growth factor stimulation
Epidermal thickening- starts in the basal layer
SCC Epidermal hyperplasia proceeds to dysplasia, carcinoma in situ and invasive squamous cell carc
can also happen with respiratory mucosa
Fibrous hyperplasia (formerly part of fibrous or fibromatous epulis, gingival hypertrophy)
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
Examples of Metaplasia
Chronic irritation in lungs
In mammary tumors
in urinary tract
Refers to abnormal development
Mostly of epithelial cells
Term mostly used in
Near-synonym: “Carcinoma in situ”
urolith, which caused compression atrophy
(xanthuinuria) with hydronephrosis, cortical and medullary atrophy and medullary fibrosis diffuse
Hyperplasia to neoplastic from left to right
sqamous cell caricoma
stomach diffuse marked with chronic gasic HYPERTROPHY
E: cryptosproidiym serpentis
Esophagus and stomach
gastric lymphoid HYPERPLASIA, multifocal
Liver, hepatocellular carcinoma with nodular hyperplasia
Kidney-hydronephrosis with secondary severe diffuse cortical ATROPHY
also ureter- hydroureter
fluid within the cell;
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.
DNA is organized around histones into nucleosomes. Nucleosomes are wound into a helix to form chromatin. Chromatin wound again into a supercoiled chromosomes.
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
Storage of genetic material
• DNA complex to protein = chromatin
o Euchromatin – uncoiled, transcriptionally active(light)
o Heterochromatin – coiled, transcriptionally inactive(dark)
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
Endoplasmic reticulum (ER)
Smooth ER (SER)
Rough ER (RER)
‒ Site of protein synthesis (esp EC)
Smooth ER (SER)
‒ Locus of enzymes that metabolize steroids, drugs, lipids, and glycogen
Synthesis of complex proteins
o Production of secretory vesicles and
Shuttles internalized material w/in cell
o Directs newly synthesized materials to cell surface or cell organelle
‒ Digest macromolecules
‒ Selectively degrades denatured
‒ Release peptides
‒ Breakdown fatty acids
‒ Generates hydrogen peroxide
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
Contents and position of cell organelles are regulated by the cytoskeleton.- cell polarity
‒ Responsible for cell movement
‒ Maintains cell shape and intracellular organization
‒ Can move organelles and proteins within the cell
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
2 Main functions
1) Selective barrier
2) Structural base for enzymes and receptors
Functions of Membrane Proteins
Evolved from ancestral prokaryotes engulfed by eukaryotes
Contain their own DNA
1) Site of aerobic metabolism- Kreb's cycle
2) Regulator of apoptosis
Which part of the nucleus is not being actively transcribed?
Spatial differences within cells is referred to as:
A. Cell structure
B. Cell polarity
C. Cell metabolism
D. Cell function
Damage or pathologic alterations in molecules and/or structure that can occur in cells and extracellular components.
N Neoplasia, Nutritional
I Inflammatory, Infectious, Iatrogenic, Idiopathic T Trauma/ Toxins
Degenerative changes are a mechanism, not an etiology
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
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
CAUSES OF CELL INJURY: PHYSICAL AGENTS
CAUSES OF CELL INJURY: INFECTIOUS AGENTS
‒ Obligate intracellular parasites; use host cell enzyme systems
‒ Cell survival depends on method viruses leave the cell
Bacteria ‒ Toxins
‒ Overwhelming and uncontrolled replication
‒ Progressive, chronic inflammatory disease
‒ Replicate in specific host cells
‒ Inflammation, tissue distortion, utilization of host nutrients
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
‒ May be transient (but not always)
‒ Results from damage to lymphoid tissue
• Viral infections
MECHANISMS OF CELL INJURY: 6 MAJOR MECHANISMS
MECHANISMS OF CELL INJURY: DEPLETION OF 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
1) Hypoxic injury
2) Toxic injury
Fundamental cause of necrotic cell death.
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
o Decreased protein synthesis
Culminates in irreversible mitochondrial and lysosomal membrane damage END STAGE NECROSIS
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
MECHANISMS OF CELL INJURY: LOSS OF CALCIUM HOMEOSTASIS
Accumulation of Ca2+--- can also drive apopsotis
• Opening of MPTP
• Enzyme activation
• Activation of caspases induction of apoptosis
MECHANISMS OF CELL INJURY: ACCUMULATION OF REACTIVE OXYGEN-DERIVED FREE-RADICALS
• Chemicals with a single unpaired electron in an outer orbit
1) Unstable configuration
2) Interacts with adjacent molecules: proteins, lipids, carbohydrates, nucleic acids, etc.
3) Initiates autocatalytic reactions
Removal of Free Radicals
Removal of Free Radicals
o Spontaneous decay: O2* + H2OO2 + 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)
Production of Free Radicals
‒ During mitochondrial respiration
‒ Absorption of radiant energy
‒ Enzymatic metabolism of drugs or toxins
‒ Transition metals (Fe, Cu)
o Degraded and removed by cell defense systems
When free radicals are low,
cells maintain a steady-state
ROS production exceeds antioxidant capacity(Typical of aging)
‒ Cell injury
‒ Degenerative disease
o Classic example: INFLAMMATION
‒ Neutrophils (Nɸ) and macrophages (Mɸ)
‒ Mediators for destroying microbes, dead tissue, etc.
Pathologic effects of free radicals
Lipid peroxidation in membranes
‒ MOA: Forms peroxidesautocatalytic 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
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 proteasesdamaged cytoskeleton ‒ Cellsstretchandrupture
Consequences of membrane damage
Mitochondrial membrane damage
‒ Opening of the MPTP↓ATP
‒ Release of pro-apoptotic proteins o Plasma membrane damage
‒ Loss of osmotic balanceinflux 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.
MECHANISMS OF CELL INJURY: DAMAGE TO PROTEINS AND DNA
o Cells have repair mechanisms for misfolded proteins o When overwhelmedinitiates apoptosis
• DNA damage
o Cells have repair mechanisms
o When overwhelmedinitiates apoptosis
Definition:Reaction of vascularized living tissues to injury.
– Involves changes in vascular bed(endothelium, connective tissue etc), blood,
– Intended to eliminate irritant and repair damaged tissue
It WILL END WITH REPAIR!
• Is a response and as such it requires an initiating stimulus (etiology)
Signs of inflammation
• Loss of function
Roles of inflammation
• Dilute, contain and isolate injury(i.e. abscess)
• Destroy invading microorganisms and/or
• Achieve healing and repair
Outcomes of inflammation
A. Ideal conditions‐ return to normal
B. Intense inflammatory response‐ attempt to separate injured tissue
C. Failure to eliminate insult‐ sequel
If immflammation returns to normal
– Elimination of the source of injury
– Resolution of inflammatory process
– Restoration of normal tissue architecture and physiologic functions
Intense inflammatory- Outcomes of inflammation (cont.)
Attempt to isolate inflammatory process, formation of a wall (such as a capsule in an abscess)
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
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
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
Inflammation ends when....
when the stimulus is eliminated
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)
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
Inflammatory extravascular fluid that has:
– a high protein concentration
– much cellular debris
– specific gravity above 1.020
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
Pyothorax in a cat
Hydrothorax in a sheep
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)
An inflammatory exudate rich in leucocytes (primarily viable and degenerated neutrophils) and parenchymal cell debris
fibrin is the main component
chronic, with lots of macrophages
Clinically can you see the difference between minimal and mild?
No, only histologically
chronic condition that is still going on
This is a case of exudative dermatitis in a pig. Name of the disease: Greasy pig disease
Usually caused by a potent stimulus
• Usually the animal has no time to respond
• Less common than acute disease processes
i.e. bee sting
• TIME: 0‐4 hours
• VASCULARI NVOLVEMENT:
– Slight edema
• INFLAMMATORY CELLS:
– Not usually numerous
– Few leucocytes
Infectious canine Hepatitis
In picture: Intranuclear inclusions within glomeruli
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.
Acute inflammation: migration of neutrophils
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
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.
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
Lymphangitis= inflammation of lymphatic vessel(s)
Thickening of serosal lymphatic vessels (chronic lymphangitis), due to Johne’s disease. Goat small intestine.
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).
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.
– Increased lymphatic drainage – Repair of endothelial damage
subacute stomatitis in a bovine
The inflammatory response usually is accompanied by an immune response.
FEATURES OF CHRONICITY:
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
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.
Inflammation of the bone
Chronic Inflammation- Vascular
• 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).
Multifocal ulcerative colitis, chronic. Feline
Inflammatory cells in Chronic Inflammation
INFLAMMATORY CELLS: Primarily Mononuclear Inflammatory Cells
– Macrophages: cells responsible for phagocytosis
and tissue debridement in a chronic lesion.
– Plasma cells
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.
Chronic lymphangitis. Johne’s disease in a goat- white chords
Definition: Single abnormality or inflamed area within a tissue
• Size: Varies from 1 mm to several centimeters in diameter
Focal lesion in the brain of a deer. Cut surface reveals presence of cloudy, yellowish material (interpreted as pus)
Focal keratitis in a bovine.
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.
Involves a considerable zone of tissue within an inflamed organ.
• Possible origins:
– 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
Locally extensive pneumonia in a pig
Althoughvariationsin severity of the inflammation may occur, the entire tissue is involved. EXAMPLE: Interstitial pneumonia.
• Diffuselesionsareoften viral or toxic in etiology.
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
– variable numbers of viable leucocytes (primarily neutrophils)
– fluids added by the inflammatory edema‐forming process.
Suppurative/ Purulent Exudate
Grey discoloration in cranioventral areas of the lung. SEVERE
FRIABLE- Locally Extensitive
Have to look at histologically
Neutrophils within alveolar spaces
Severe suppurative pyelonephritis in a dog
Pyometra in a dog: a form of severe suppurative inflammation
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.
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
• GROSS APPEARANCE: is yellow‐white to gray‐ white and varies from watery to viscous depending on fluid content.
Chronic Suppurative Osteomyelitis
can be called a veretral abyses
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
What is the first step to adhension?
FORMS A PSUEDO LUMEN
the surface of the mucosa
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
DIFFUSE SEVERE FIBRINOSUPPURATIVE PERICARDITIS‐ PORCINE
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.
Fibrinous pleuritis in a horse- Severe, diffuse
Pleural surface covered by friable material
Homogeneous, eosinophilic material . Bacterial colonies (arrows) are basophilic with HE stain
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.
fibrous connective tissue adhesions
Epicardial surface covered by fibrin Fibrinous pericarditis
Cut surface demonstrating thickenning of bile ducts Chronic fibrosing cholangitis
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.
• 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.
Serous exudate- can tell from seperation of the membrane
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.
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.
Diffuse granulomatous inflammation
“cerebroid” appearance of affected intestine
ETIOLOGY: usually some non‐digestible organism or particle which serves as a chronic inflammatory stimulus, delayed‐type hypersensitivity is often required.
• Mycobacterium, Actinomyces, Blastomyces,
– Noninfectious AGENTS: Mineral oil, Complex polysaccharides, Foreign bodies
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.
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.
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.
ACUTE OR CHRONIC? Acute- no fribrosis
segemental hemorrhagic enteritis
Diffuse severe hemorrhagic cystitis
MUCOPURULENT OR CATARRHAL
heinflammatory exudate is composed of mucus and pus (neutrophils and cell debris).
Bovine‐ Catarrhal rhinitis
– Basophils and Mast cells
Lymphocytes and plasma cells. – Monocytes and Macrophages – Platelets
Cell on the left= Polymorphonuclear Leukocytes
Leukocytes are normal inhabitants of the circulating blood (except plasma cells, and mast cells).
Each cell type plays a fairly distinctive role
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.
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
The purpose of Neutrophils is to eliminate:
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.
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:
– 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.
Neutrophils, fluid and fibrin within the alveolar spaces
Neutrophils within a bronchi
neutrophils in blood
NEUTROPHILS IN TISSUES Suppurative exudate
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
– lysosomal enzymes
Neutrophils mediate tissue injury via release of oxygen free radicals and lysosomal enzymes.
They regulate inflammatory response via releasing chemical mediators such as leukotrienes and platelet activating factor.
Suppurative endometritis‐ cow
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.
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.
Granules in Eosinophils
• 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 (*)
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.
Eosinophiliccationicproteincontributesto parasite killing and also shortens coagulation time and alters fibrinolysis.
Eosinophils are also effective in killing
Eosinophils are also effective in killing helminth parasites by antibody‐dependent cell‐mediated cytotoxity.
Eosinophiles in blood
Functions of Eosinophils
Modulate hypersensitivity reactions ‐ especially Immediate type
• Defence against helminthic infestations
• Phagocytic but less active phagocytes than neutrophils
EXAMPLES OF EOSINOPHILIC INFILTRATION
Allergiessuchas contact dermatitis
• Habronemainfectionin horses.
• Eosinophilsarealso prominent in mast cell tumours, particularly in dogs.
LYMPHOCYTES AND PLASMA CELLS
• 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.
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.
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.
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.
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)
PHAGOCYTOSIS: macrophages are the major scavengers in the inflammatory response.
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)
EVENTS OF ACUTE INFLAMMATION
2. Vascular changes
3. Cellular events
4. Termination of acute inflammatory response
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
– Increased vascular permeability (capillaries and post‐capillaries)
extravasation= delivery of white blood cells to the site of injury
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
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
– Endogenous: such as chemical mediators (component
of Complement system or lipoxygenase pathways) – Exogenous such as infectious agents
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
Termination of the acute inflammatory response
Degradation of mediators of inflammation
• Stop signals are produced once stimulus is gone
– 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
Severe multifocal to coalescent dermatitis.
Etiology: Turkey pox virus
Bilateral locally extensive pneumonia
Fibrino-nectroizing enteritis. Pig ileum
DIFFUSE SEVERE FIBRINOUS PLEURITIS
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
OUTCOME 2‐ HEALING BY FORMATION OF SCAR TISSUE
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.
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.
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,
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.
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.
Hepatic granulomas in a red tailed hawk. Etiology: Mycobacterium avium sp
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)
Multifocal granulomas in the air sacs Etiologic diagnosis: Mycotic Airsacculitis- Aspergillis
Granuloma in the lung.
Fungal organisms stain pink with PAS stain
Fibrous= fibrosis= fibrous connective tissue= formed by fibroblasts and collagen= chronic
Cells Involved in Granulomatous Inflammation
• Multinucleated giant cells
multinucleated giant cells
Macrophages are the sources of the multinucleated giant cells, which are believed to be formed by the coalescence of single macrophages.
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
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.
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
Caseous necrosis, multinucleated giant cells and clusters of lymphocytes
close up of a granuloma
Pattern of chronic Inflammation
Two gross patterns are possible:
– diffuse thickening of affected tissue (eg.: Johne's
– solid, firm, nodular lesions (eg: Blastomyces
dermatitidis) which may compress adjacent tissue.
• These lesions may contain organized granulomas with necrotic or suppurative centres.
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.
if significant numbers of neutrophils are present in the centre of a granulomatous reaction, the term pyogranulomatous inflammation is often used.
organized accumulation of macrophages and epithelioid cells, often rimmed by lymphocytes.
granuloma with a central area of necrosis
necrosis may lead
– necrosis may lead to calcification / mineralization
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).
This type of diagnosis is restricted to two words only - the causative agent and the site of the lesion (i.e., parvoviral enteritis).
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).
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
sequence of events from initial stimulus to the ultimate
expression of the disease in the response of cells or tissues
to the etiology (oropharyngeal infectionviremiainfection and death of rapidly dividing cells (enterocytes) from cryptsnecrohemorrhagic enteritis)