Intro

• Pathogenesis is the mechanism of disease development ie the sequence of events occurring following exposure to the inciting agent or event.
• Morphologic diagnosis is based on the predominant lesions and refers to structural changes seen in cells or tissues in association with disease.

  Aetiologic diagnosis identifies the specific aetiology (cause)
• Fresh samples must be fixed promptly in 10-20x sample volume of formalin. Otherwise tissues will begin to autolyse. Samples should be sent in wide topped containers so they are easy to remove once fixed. certain techniques may require different fixatives or the tissue to be frozen.
• The stain routinely used in diagnostic pathology is H+E

  Fat – Oil red O

  Glycogen – PAS (periodic acid-schiff)

  Iron – Haemosiderin Blue

  Connective tissue – masson’s trichrome

  Basement membranes – jones’ stain

  Immunohistochemistry – depends on stain aim
• Hypoplasia – incomplete or underdevelopment of tissue or organ
• Aplasia – organ doesn’t develop at all
• Agenesis – failure of any development due to lack of embryonic primordial tissue
• Hypertrophy – increase in size of cells (no new, just bigger)
• Hyperplasia – increase in number of cells
• Metaplasia – one adult cell type is replaced by another
• Dysplasia – alteration in shape or organisation of a tissue
• Potential causes of cell injury:

  Hypoxia (main cause) by reduction in oxygen supply to cells

  Physical agents e.g. trauma, high/low temp, ionizing radiation

  Infectious agents

  Chemicals, drugs, toxins

  Damaged cells do not necessarily die but severe or prolonged injury can lead to necrosis associated with raised intracellular calcium levels.
• hydropic degeneration: Cellular swelling (drawing in water), often due to hypoxia. Reduced ATP levels cause a switch to anaerobic metabolism, depleting glycogen and causing lactate and inorganic phosphates to accumulate. Membrane Na/K pumps are inhibited by lack of ATP and water moves into the cell.
• In coagulative necrosis basic cell outlines are preserved due to delayed proteolysis. An example is renal infarct. This is a form of acute necrosis
• caseous necrosis: Friable ‘cheese’ like appearance occurring as a result of a chronic lesion. May develop dystrophic calcification. E.g. in TB
• liquefactive necrosis: Cavity or cavities are filled with liquefied debris. E.g. cns lesions as there is little fibrous tissue framework to support dead cells. OR abscesses, caused by pyogenic bacteria
• Fat necrosis: the specific necrosis of fat e.g. pancreatic fat necrosis (enzymatic) or traumatic necrosis
• karyorrhexis: A histologic feature of necrotic cells where the nucleus ruptures
• karyolysis: A histologic feature of necrotic cells where the nucleus lyses but its architecture is maintained
• pyknosis: A histologic feature of necrotic cells where the nucleus appears small, shrunken and stains very densely
• Lipidosis is the accumulation of intracytoplasmic lipid. This occurs particularly in the liver, kidney, heart and skeletal muscle.

   

  The central role of the liver in lipid metabolism means it is especially susceptible

   

  The 2 major mechanisms are through excessive FFAs entering the liver (through diet or adipose tissue breakdown) or toxic damage affecting metabolism of FAs and TGs
• Fatty infiltration is the REPLACEMENT of cells by adipocytes due to old age or obesity. Lipidosis is the accumulation of fat within cells.
• Glycogen accumulation in the liver may result from corticosteroid therapy, diabetes mellitus (can also damage the kidneys leading to glycogen nephrosis) or via glycogen storage disease.
• apoptosis can be identified microscopically by Condensation of chromatin, fragmentation and budding of cytoplasm. Cells appear shrunken but there is no associated inflammation
• In dystrophic calcification serum calcium levels are normal but calcium is deposited into tissue that is already dead or dying due to cellular damage interfering with their ability to regulate calcium.

  In metastatic calcification the primary problem is hypercalcaemia which damages intracellular organelles. Examples include renal failure due to secondary hyperparathyroidism, hypercalcaemia associated with malignancy and vitamin D toxicity.
• Serous exudate occurs early in most acute inflammatory lesions due to separation of connective tissue fibres with fluid e.g. burns, blisters. Clear or yellowy watery fluid with no or very few cells.
• Catarrhal exudate occurs in the respiratory and GI tracts in acute inflammation where mucous secreting cells are prominent. Thick and gelatinous consistency containing some connective tissue cells separated by mucous and/or hyperplastic epithelium
• Fibrinous exudate occurs in acute inflammation where damage is more severe allowing larger proteins (like fibrinogen) to leak through endothelium. Most common in body cavities as a result of infections. The surfaces of organs appear red due to active hyperaemia and covered in white/yellow exudate. Histologically has a high concentration of plasma proteins and no/few cells. Fibrin meshwork stains bright pink
• In acute inflammation, suppurative/ purulent exudate is often bacterial in origin, particularly staph, strep and e. coli. Grossly it is thick white/yellow material, often liquid but can dry out and become congealed or laminated. Histologically contains many plasma proteins and high cell count (mostly neutrophils)
• formation of fibrin in fibrinous exudates: Increase vascular permeability as an inflammatory response allows escae of plasma proteins including fibrinogen. The fibrinogen then forms fibrin i.e. fibrin formation is local and acute
• a solitary lesion is focal

  multiple lesions is multifocal. they may coalesce (merge together)

  diffuse lesions involve the whole organ

  Miliary is many very small lesions all over the organ

  Segmental involves a lesion on a portion of tube e.g. intestines
• Conclusions in post-mortem require access to how the animal died, when the animal died and the conditions postmortem (fridge/ field etc)

  Ø  Euthanasia (barbiturates may affect organs), abattoir specimens (bled out so will appear pale), at rest or exercise?

   
• lesions can be interpreted based on

  Size

  Consistency – type (soft/firm/hard), degree (slight/moderate/marked), cohesion (friable/elastic)

  Odour

  Blood/exudates

  Cut surface- does it enter the body of the organ?
• ways in which lesion shape can be described:

  Circular, oval etc.

  Well demarcates (clear borders) or poorly demarcated (irregular borders)

  Surface – flat, elevated, depressed, umbilicated (focal and deep), pedunculated (bump on a stump), sessile (elevated with a broad bade attachment)
• A cranioventral lesion distributed in the lungs suggests an inhaled pathogen (aerogenous portal of entry)
• a raised lesion suggests Something has been added- common in parasitic and cancer e.g. inflammatory reaction around migrating larvae
• A Red/ red-black lesion suggests haemorrhage or congestion. If nodular, consider a haematoma or a vascular lesion or neoplasm
• A Black/ brown-black lesion suggests melanin containing neoplasm or melanosis (non-neoplastic accumulation of melanocytes) or pseudomelanosis (postmortem colour change from bacteria producing hydrogen sulphide which converts tissue iron to iron sulphide)
• A Green lesion suggests bile pigment, common in areas local to the bile duct due to biliary imbibition. May also be caused by some fungal pathogens of the respiratory tract.
• A Yellow lesion suggests Fat, bilirubin, fibrin, exudates, neoplasms, icterus