General Pathology

*Karyorhexis

fragmentation of the nucleus

forensic pathology

medicolegal

*Metaplasia

transformation or replacement of one adult cell type with another (associated with neoplasia)

general pathology

types and mechanisms of disease (all organs)

*calcinosis

widespread excessive calcification

gross appearance of a fatty change

yellow discoloration, enlarged

subacute

"not very acute" imprecise

Coagulative Necrosis

Coagulation of proteins in the tissue via heat, chemicals, ischemia or bacterial toxins.

Algor Mortis

Cooling of the body after death

Lesion

An abnormality or interruption of normal structure function or both

intracytoplasmic inculsions

RNA viruses; rabies

Cell Injury

Any change that results in loss of the ability to maintain the normal or adapted homeostatic state. Can be reversible or irreversible

Pathogenesis of Fatty Change

Increased mobilization of fats, injury to cells due to toxins or anoxia, deficiencies in methionine or choline.

Ischemia

Infarction, complete loss of blood flow (leads to necrosis of the tissue)

General Pathology

Looks at cellular and tissue levels, mechanisms of disease for all organs

Causes of Necrosis (7)

Loss of blood supply (ischemia) Loss of nerve supply Loss of endocrine stimulation Endotoxins Mechanical/thermal injury Chemical injury pressure

*Erosion

Loss of epithelium with an INTACT basement membrane

Gangrenous Necrosis

Necrotic tissue invaded by saprophytic or putrefactive bacteria. 2 types: moist and dry

Morphologic Signs of Subcellular Injury

Nuclear Change, Ultrastructural Changes, Phospholipid Accumulation, Lysosomes

Hallmarks of Necrosis (4)

Passive cell death Doesn't require energy Affects large numbers of cells Associated with injurious results

Amyloid

Pathologic protein substance that forms Beta Pleated sheets of non branching fibrils. Lead to gross appearance of an enlarged, pale, waxy translucent organ. Micro appearance shows substance deposited along basement membranes and between cells.

Classification of Amyloid

Primary vs. Secondary Systemic vs. Localized

Apoptosis

Programmed Cell death requiring energy and certain enzymes (active process) no inflammatory response

*Apoptosis

Programmed cell death that occurs to: delete unnecessary cells normal involution regression of hyperplasia deletion of genetically unstable cells activation of viruses activation by immune cells mediated by caspases requires energy *DOES NOT ELICIT INFLAMMATION*

*Hyperplasia

Proliferation (#) of cells in organ or organ tissue

acute

changes (good or bad) occurring rapidly

*Involucrum

connective tissue capsule surrounding a sequestrum (middle)

necrosis

death of cells and tissues while the body is still living; some cells and tissues are dead

Pathognomonic

diagnostic for a particular disease that means the disease is present without a doubt

*gross appearance of coagulative necrosis

firm, pale, dry tissue that retains its original form. eventually becomes easily friable (easily crumbled), and it is often surrounded by a reddened area of hyperemia

clinical significance

functional consequences of morphological changes

Livor mortis

gravitational settling of blood before it clots

pathogenesis of gout

kidney failure disturbance of purine metabolism common in high protein diets

coagulative necrosis

likely due to an infarct

*Four causes of coagulative Necrosis

local heat local chemicals ischemia bacterial toxins

chronic

long-lasting

*Karyolysis

loss of the nucleus

Pathogenesis

mechanisms of development of a lesion or disease process

Sequestrum

necrotic tissue in the middle of a lesion

Sign

objective; seen by observer

systemic pathology

organ and system

gross appearance of cell swelling

organ is often pale, enlarged, swollen (rounded margins, heavy, wet), bulges on the cut surface

Infarction

the obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue

Systemic Pathology

Examines organ systems

Fat Necrosis

Fat and glycerine combine with metallic ions to form soap (road kill grease spot) Gross: Loss of shine, firm soaplike consistency Micro: cell outlines remain but cytoplasm replaced by pale blue material

does apoptosis elicit inflammation?

NO!!!

characterizes apoptosis?

apoptic bodies caspases (histo stain)

*cholesterol crystals

areas of previous hemorrhage or inflammation. ex: found in the center of horse brains

Hyaline Change

at the cell level, appearance of solid glossy semitransparent material

microscopic appearance of coagulative necrosis

-Tissue organization remains *-Cell outline remains but with a loss of cellular detail -Nuclear changes -Cytoplasmic coagulation and hypereosinophilia.

*apoptosis: physiologic situations (6)

1. embryogenesis 2. hormone dependent involution 3. cell deletion in proliferating pools 4. death of senile cells 5. elimination of self reactive lymphocytes 6. cell death induced by cytotoxic T-cells

*morphologic hallmarks of irreversible cell injury and death

-severe mitochondrial swelling -large flocculent densities in mitochondrial matrix -increased loss of proteins, enzymes, co-enzymes -greatly increased membrane permeability

Four causes of fat necrosis

1 Pancreatic fat necrosis (secondary to pancreatic disease with release of enzymes that break down fat). cats and dogs 2 vitamin E defiency: food and fiber animals 3 Traumatic fat necrosis: lying on hard surface 4 metabolic fat necrosis: mesenteric and omental fat become firm around the viscera; cattle

*Hallmarks of Cell Degeneration (11)

1. Cell swelling 2. Fatty Change 3. Glycogen Accumulation 4. Lipofuscin and Ceroid (color changes due to oxidation) 5. Hyaline Changes 6.Amyloid deposits 7. Mucinous Changes 8. Calcification 9. Gout 10. Cholesterol Crystals 11. Inclusions

Signals of Cellular Hypertrophy (2)

1. Increased protein content of cells 2. Increased organelle number

*3 Agents that cause Caseous necrosis

1. Mycobacterium (TB) 2. Corynebacterium pseudotuberculosis 3. Rhodococcus equi

3 types of desequamation

1. erosion 2. ulceration 3. slough

*sites of damage in cell injury (remember picture in notes)

1. mitochondria 2. lysosome 3. plasma membrane

What is Pathology?

A bridge between basic and clinical sciences that studies the structural and functional changes in cells, tissues and organs to explain how or why the clinical signs of disease are manifested.

Inclusions

A characteristic of certain viral diseases.

Lipofuscin

A pigment that collects in cells leading to a gross appearance of brown discoloration and a micro appearance of brown pigment in cells

Calcification

Abnormal deposition of calcium salts in soft tissues. Leads to a gross appearance of chalky, white tissue that is gritty on cut surface

Glycogen Accumulation

Accumulates due to severe, prolonged hyperglycemia, presence of high levels of glucocorticoids, and in lysosomal storage diseases.

*Gout

Accumulation of urate crystals. Gross: white, firm crystal deposits. Micro: granulomas with radiating crystalline material.

*Hypertrophy

Cell enlargement resulting in enlargement of organs (NOT PROLIFERATION)

*Targets of cell injury (4)

Cell membrane Aerobic respiration (mitochondria) Protein Synthesis (rough ER, ribosomes) Preservation of genetic integrity (nucleus)

*Atrophy

Cell shrinkage due to disuse, reduction in the mass of a tissue or organ- can be reversible if not prolonged

Types of Necrosis (4)

Coagulative Necrosis Caseous Necrosis Liquefactive Necrosis Gangrenous Necrosis

*Results/outcomes of necrosis

Consequences include: organ dysfunction removal of necrotic tissue scar formation calcification of dead tissue liquefaction and removal by macrophages/lymph abcess formation sequestration Erosion Ulceration Sloughing

intranuclear inclusions

DNA viruses

Hypoxia

Decreased blood oxygen supply, decreased blood flow

*Ulceration

Destruction of the basement membrane

*Cell Swelling

Early, almost universal sign of injury due to loss of volume control. results from loss of control of ions/water with net uptake of water

Caseous Necrosis

Firm, gritty yellowish cheeselike appearance. Can be encapsulated in fibrous capsule, caused by bacterial infection and tissue breakdown

*causes of liquefactive necrosis

Found regularly in CNS due to low amounts of coagulative protein, high amounts of lipids and low pH. Abcesses: also qualify with liquid center of pus and surround of connective tissue. caused by bacteria and neutrophils that release proteolytic enzymes that liquefy tissue.

Liquefactive Necrosis

Gross: a fluid filled cavity in a tissue. usually colored with a soft consistency, usually smelly, can be surrounded by fibrous capsule Micro: pink proteinaceous fluid with edges made of frayed tissue

Appearance of Caseous Necrosis

Gross: dry but greasy, firm, usualy pale to white, easily separated Micro: Loss of all tissue outline, amorphous, granular debris, infiltrated with macrophages and multinucleated giant cells.

Symptom

Subjective; experienced and described by patient

*Fatty Change

The accumulation of neutral fats in a cell (not adipose). Common to injured cells and sick cells tend to accumulate TG, especially those whose function is to metabolize lipids. (hepatocytes, myocardial cells, renal tubular epithelial cells)

*Zenker's Necrosis

Type of coagulative necrosis specific to striated muscle (skeletal or cardiac) "white muscle disease" Gross: slightly swollen muscle, waxy appearance, light in color Micro: Preservation of tissue organization and cell outline, karyolysis of nucleus

Forms of Gout (2)

Visceral and Articular

Causes of Zenker's Necrosis

Vitamin E deficiency Ischemic Necrosis Bacterial toxins leading to muscle lesions

pathogenesis of cell injury

physical agents chemical agents infectious agents nutritional imbalances genetic defects

Etiology

primary cause of disease

pathogenesis of glycogen accumulation

prolonged severe hyperglycemia, increased corticosteroids, enzyme deficiencies

outcome of coagulative necrosis

removal thru slow digestion progression to liquefactive necrosis mineralization sequestration

*Slough

shedding of a large amount of tissue (think burns)

desequamation

shedding of dead tissue from a surface

*Pyknosis

shrunken, dense nucleus (condensation)

syndrome

signs and symptoms together

what substance is present within adipose cells during fat necrosis?

soap

Morphologic changes

structural alterations within cells, organs, tissues associated with disease processes

Anatomic pathology

studies whole animals and tissues; looks at tissue changes (histology)

Clinical pathology

studies whole animals, cells, fluids (blood, urine), and biochemistry; cell by cell changes

morphologic pathology

surgical and anatomic: biopsy, necropsy, autopsy

gross appearance of glycogen accumulation

swollen organ, rounded margins, increased palor

gross appearance of necrotic tissue

tends to be lighter in color (unless filled with blood, then its darker); color due to loss of cytochrome oxidases

Autolysis

the destruction of tissues or cells of an organism by substances produced in the organism (i.e. enzymes). self digestion. Occurs after death, PM degenerative changes

necrobiosis

the natural death of cells or tissues thru aging, as distinguished from necrosis or pathological death