Exam 1: Types of Necrosis

1. Ischemia caused by obstruction in a vessel may lead to coagulative necrosis of the supplied tissue in all organs except the brain (WHY?) 2. A localized area of coagulative necrosis is called INFARCT 3. Sequelae: Death due to organ dysfunction or scarring

***Define Infarct

*Leuko: white, Encephalo: brain, Malacia: softening -Disease of horses -Caused by ingestion of **fumonisin B1 toxin produced by the fungus Fusarium verticillioides on moldy corn -25% of exposed animals are affected and the death rate is high in affected horses -There is no known treatment; prevention is the key. (Examine the corn for pink fungi)

***Define Leukoencephalomalacia

-Coagulative necrosis of striated muscle (so in myocardium and skeletal muscle)--loss of striations, vacuolation of cyto, increased eosinophilia, and pyknosis, karyolysis, karyorrhexis -Causes: 1. Plant toxic (know any that are prominent in Indiana?--WHITE SNAKE ROOT) 2. Bacteria (Clostridium chauvoei) 3. Vitamin E- Se deficiency (white muscle disease) 4. Exertional ("capture") myopathy 5. Ischemia

***Define Zencker's Necrosis

Lesions: focal necrosis of the white matter of the cerebral hemispheres -The affected areas appear yellow, soft, hemorrhagic, and cavitated, with gelatinous fluid in the spaces -The lesions may be bilateral, but not necessarily symmetrical -Swine develop pulmonary edema and hepatic necrosi after infusion of high doses of fumonisin

***What are the lesions associated with Leukoencephalomalacia?

1. Definition: form of necrosis in which the architecture of dead tissues is preserved for a span of at least some days -Preservation of basic cell outlines 2. Presumably, the injury denatures not only structural proteins but also enzymes ***Blocks the proteolysis of the dead cells 3. Ultimately the necrotic cells are removed by phagocytosis and by digestion of the dead cells by the action of lysosomal enzymes of the leukocytes

Define Coagulative Necrosis (or coagulation)

-Definition--Liquefactive is characterized by tissue that has liquefied due to the action of hydrolytic enzymes, primarily from neutrophils (staph and strep are common causes) -Occurrence 1. Abscess (Occurs anywhere, a localized collection of pus (liquid inflammatory debris), elicited by certain bacterial agents (pyogenic) that attract neutrophils) 2. CNS (Characteristic pattern of ISCHEMIC NECROSIS in nervous tissue, especially brain and spinal cord, see even without PMNs-often neutrophils are not present, tissue lacks proteins (no coagulation))

Define Liquefactive Necrosis

Abscess-->bacterial emboli spread via blood-->disseminated abscesses --> +/- death due to septicemia

Define Pyemia

Abscessed walled off--> resorption of debris +/- mineralization--> scar

Define Resolution

bacteria plus bacterial toxins in the blood can cause hemodynamic changes and/or cell injury (sepsis)

Define Septicemia

Definition: necrosis of adipose tissue due to action of lipases -Occurrence: Subcutaneous fat and Mesenteric fat -Sequelae: 1. Incidental finding 2. With pancreatitis--death due to shock 3. Scarring 4. Interference with organ function

Explain Fat Necrosis

-Cytoplasm is homogenous and eosinophilic (coagulation of cell proteins) -Out line of cells and architecture remains -Dead cells appear as "ghosts" -Nuclei: 1. Pynosis 2. Karyorrhexis 3. Karyolysis 4. Absence of nucleus -Inflammation

Explain histological representations of coagulative necrosis

Mesenteric fat--opaque, white, firm to hard, granular, gritty on cutting Subcutaneous fat--opaque, yellow to brown (due to ceroid pigment), firm, lumpy **Looks different than the adjacent tissue that is also fat

Explain the gross appearance of fat necrosis?

-Outline of adipocytes may be present -Fat replaced with amorphous to granular material with variable staining (material represents fatty acid soaps) -Inflammation--PMNs, macrophages -Fibrinosis

Explain the microscopic appearance of fat necrosis?

1. Abscess -Microscopic to large -Well-circumscribed - +/- fibrous capsule -Center filled with pus--(opaque; white, tan, green; liquid, viscous or semisolid (inspissated) consistency, +/- bacterial granules ("sulfur") or mineral - +/- foul odor -Large number of neutrophils plus necrosis of parenchyma (presence of neutrophils does not equate to an abscess) -Fibrous capsule, mineralized debris in older lesions 2. CNS -Malacia=softening - +/- depressed -Yellow to brown -Cavitation=fluid-filled soft frayed edges -Decreased density of tissue, pale eosinophilia, poorly defined edges - +/- phagocytic cells (Gitter cells)

Explain what should be expected with liquefactive necrosis grossly

1. Thrombus-->hypoxia/anoxia-> myocardial infarct 2. "Downer cow"--necrosis of thigh muscles dues to ischemia 3. Anemia-->hypoxia-->centrolobular hepatic necrosis 4. Herpesvirus infection-->viral induced cytolysis--> multifocal hepatic necrosis

Give an example of Coagulative Necrosis (or coagulation)

Polio=gray, encephalo=brain, malacia=softening -Disease of ruminants -Cause is often not known Deficiency of thiamine or a disturbance in its metabolism is implicated in PEM (Thiaminase-producing bacteria that proliferates after CHO ingestion can destroy thiamine, Thiaminase-producing plants, such as bracken fern) Ingestion of high sulfur-containing diets;sulfite an intermediate in the reduction of sulfate, can cleave thiamine into consisuents thereby rendering it inactive; Dietary deficiency in thiamine) -Treatment of early cases consists of administration of thiamine and can be quite successful

***What is Polioencephalomalacia?

Pathogenesis: not well worked out; sphingolipids are components of cell membranes and especially rich in nervous system; build up of free sphinganine causes direct cellular toxicity Ingestion of moldy corn-->elevated levels of fumonisin B1 in the body--> fumonisin B1 bonds to ceramide synthase-->inhibition of this enzyme--> decreased production of sphingolipids and toxicity from sphinganine-->necrosis of white matter in the brain

***What is the pathogenesis of Leukoencephalomacia?

-Thaimine is a co-factor or coenzyme in a number of important metabolic reactions. Thiamine is a cofactor in the hexose monophosphate shunt which is the major metabolic pathway for glucose in the brain -Thiamine also serves as coenzymes in the Krebs cycle -Deficiency of thiamine results in a reduction in the sodium-potassium pump and subsequent loss of osmotic control Thiamine deficiency (maybe carb overload)-->decreased energy (why?!)--> decreased Na-K pump-->loss of osmotic control--> necrosis of neurons

***What is the pathogenesis of Polioencephalomalacia?

-Initial change is edema, as evidenced by swelling of gyri -Cerebral laminar necrosis that gives a yellow color to the gray matter -Microscopically Early: edema, necrosis of neuronal cells bodies, and endothelial cell swelling Later: loss of neurons and vacuolation of the neutrophil After: 7-10 days, macrophages (gitter cells) invade the area to ingest the myelin and cell debris -Undigested membrane debris reamins within the macrophages as ceroid pigment; this pigment floursces under UV light

***What lesions are normally associated with Polioencephalomalacia ?

1. Removal of debris by phagocytes 2. Healing by gliosis--proliferation of fibrillary astrocytes, NOT fibrosis 3. Loss of function--signs attributed to area(s) affected

List possible CNS sequelae of liquefactive necrosis

1. Pyemia: Abscess-->bacterial emboli spread via blood-->disseminated abscesses --> +/- death due to septicemia 2. Septicemia: bacteria plus bacterial toxins in the blood can cause hemodynamic changes and/or cell injury (sepsis) 3. Resolution: Abscessed walled off--> resorption of debris +/- mineralization--> scar

List possible abscess sequelae of liquefactive necrosis

1. Abcesses cause by pyogenic bacteria (Staphylococcus, Streptoccoccus, Cornebacterium) 2. Myelomalacia due to ruptured intervertebral disc (dogs) 3. Equine leukoencephalomalacia ("Moldy Corn Disease")

List possible examples of Liquefactive Necrosis

1. Coagulative Necrosis -Infarct -Zenker's Necrosis 2. Liquefactive Necrosis 3. Caseous Necrosis 4. Gangrenous Necrosis 5. Fat Necrosis

List the possible classifications of necrosis

Ischemia 1. Thrombus, embolism 2. Torsion (Twisting along longitudinal axis) 3. Volvulus (Twisting around its mesenteric axis) 4. Chronic vasocontriction (Ergot) 5. Mechanical compression (bandage) OFTEN unfortunately 6. Freezing -Aspiration pneumonia due to inhalation of irritating gastric contents -Bacterial toxins--especially mastitis

What are possible causes of Gangrene?

1. Acute anoxia (e.g. ischemia) 2. Acute toxic injury 3. Certain bacterial and viral agents 4. Sequelae: removal of debris with scarring or regeneration

What are possible causes of coagulative necrosis?

Dry gangrene of the pinnae 1. Freezing-->vasocontriction and increased blood viscosity--> hypoxia/anoxia-->dry gangrene 2. Salmonellosis in pigs-->andotoxin damages blood vessel-->endothelial damage +/- fibrinoid degeneration--> thrombosis and vasculitis--> dry gangrene

What could be the pathogenesis of dry gangrene of the pinnae?

Dry Gangrene: Coagulative necrosis, Line of demarcation= leukocytes Moist Gangrene: Coagulative + liquefactive necrosis, +/- gas bubbles, line of demarcation

What does (dry and moist) gangrene look like microscopically?

-Localized; well demarcated -Soft, friable, gray-tan material resembling cheese -Dry and crumbly or soft and pasty - +/- gritty on cutting due to mineralization - +/- laminated on cross-section (esp. C. pseudotuberculosis

What does Caseous necrosis grossly look like?

-Center of lesion without cell or tissue architecture -Center with granule, eosinophilic debris, basophilic nuclear remnants, basophilic mineral -Peripheral with macrophages, other inflammatory cells, +/- fibrous connective tissue

What does Caseous necrosis microscopically look like?

Dry gangrene -See external locations (Areas with limited circulation, See in areas where moisture from necrotic tissue can evaporate) -Gross appearance is more like coagulative necrosis -Area dry, shriveled, leathery, dark red to black -Cold, lacks sensation -Red line of demarcation between necrotic and viable tissue

What does dry gangrene look like grossly?

-See in internal organs and mammary gland (areas where blood vessels are abundant) -Gross appearance like liquefactive necrosis -Tissue dark red to black -Soft, moist, friable -Foul odor - +/- gas bubbles, crepitant on palpation (gas gangene) -Line of demarcation

What does moist gangrene look like grossly?

Cause of Gangrene: Disease of ruminants caused by Clostridium chauvoei -Hemorrhage and myonecrosis due to bacterial toxins, gas bubbles in muscle

What is Blackleg?

Caseous is a general term meaning resembling coagulated protein or curds -It was originally defined by its gross appearance which is a combination of liquefactive and coagulative necrosis -Caseous necrosis is characteristic of certain bacterial infections and has a distinct appearance Occurence: in any tissue, see with Myobacterium bovis (disease=bovine TB), see with Corynebacterium pseudotuberculosis (disease=ovine caseous lymphadenitis) Sequelae: encapsulation and persistence; or healing by scarring

What is Caseous necrosis?

-Caused by the ingestion of toxic alkaloids (erotamine) produced by the fungus Claviceps pupurea (the fungus infects seed heads of grasses) -Causes direct stimulation of the arteriolar smooth muscle resulting in marked vasoconstriction; leading to ischemic necrosis -Typically affects cattle after 1 week on infected grain -Lesions begin at the coronary band and result in dry gangrene -Feet, tips of ears, teats, and tail can be affected

What is Ergot poisoning?

Definition: represents ischemic injury modified to varying degrees by exposure to air (dry gangrene) or by the liquefactive action of bacteria (moist or wet gangrene)-->clinical term, not a specific pattern of cell death Occurence: -External--extremities, such as limbs, ear, combs -Internal--lung, intestine Sequelae -Death due to toxemia, especially with gangrene of internal organs ex GI twist -Sloughing--especially with gangrene of external tissues

What is Gangrenous Necrosis (gangrene)?

Cause of gangrene: disease of ruminants caused by Clostridium septicum -Edema and hemorrhage (due to bacterial toxins), as well as gas in subcutis and fascial planes of muscles -Horses and pigs also susceptible

What is Malignant edema?

-Necrotic tissue may have varied gross and microscopic characteristics -Appearance dependent on processes in tissues, blood flow, and nature of the inciting agent ***The type of necrosis can give a clue as to the cause and/or pathogenesis -Variation within each type due to agent, extent of lesion

What is the value in identifying the classification of necrosis?