General Pathology

General Pathology

1. cellular injury

   • split into reversable or irreversable- not clear cut
   • effect on cell depends on agent, duration, blood supply and cell type
   • characteristics of irreversible cell degeneration: plasma membrane damage/ calcium entry/ mitochondria swelling and vacuolation/ lysosomal swelling and vacuolisation. increase in reactive oxygen species

2. Hydropic degeneration

   • 1-accute cellular swelling- causes include hypoxia, viral infection, toxins
   • 2- hypoxia- decrease ATP production
   • 3- sodium and watermoves into the cell, potassium moves out
   • 4-water moves into cell- cisternae of ER distend and rupture- vacuolation
   • foamy appearance at microscopic level
   • this stage is transient

3. Fatty change

   • appearance
     • accumulation of fatty substances in cytoplasm of specific cells- NOT BODY FAT STORES
     • problem with fat uptake/ catabolism/ secretion can lead to fatty change
     • Gross Change- liver big, tan colour, prone to rupture. parenchyma bulges on sectioning, heart flabby and streaky papillary muscle
     • microscopic change- liver and kidney- vacuoled of different size in cytoplasm. nucleus pushed to periphery. stain oil red o or sudan black. must stain in frozen sections
   • causes
     • dietary factors
       • starvation- increased mobilisation of fat stores and liver can't cope
       • over eating- fat stored in liver before moving to body fat stores
       • lipotrope dearrangement- lipotropes increase removal of fats from leaver. a decrease in them results in a decrease in fat removal
     • metabolic disease
       • and toxins
       • derranged carbohydrate metabolism
       • diabetes mellitus incrase demand for glucose mobalise fat stores
       • ketosis- demand for glucose in twin lamb or milk fever
       • hypoxia- anamia or ischaemia
     • distribution
       • dilute and uniform- diet or metabolism. zonal- circulatory disease

4. mucoid degeneration

   • degeneration of connective tissue due to deposits of mucinous material in ECM
   • e.g. valvular endocardiosis
   • decreased amount of collagen and irregular structure
   • mucous metaplasia at epithelial surfaces- trap pathogens etc.

5. hyaline degeneration

   • "glassy"
   • umbrella for lots ot types of degeneration
   • microscopic- stain pink and red looks structureless
   • Hyaline degeneration- skeletal muscle
   • hyaline casts- in urine in animals with urine failure and proteinurea
   • hyaline membranes- layers of protein adhereing to damaged alveoli

6. fibrinoid degeneration

   • increase in fibrin
   • red smudges in blood vessels
   • degenerate muscle and elastic fibres
   • local hypersensitivity type III or hypertension

7. Amyloidosis

   • polymerisation of abnormal peptides forming fibrillar proteins
   • stimulus0 misfoled precursor protiens
   • causes- chronic inflammation, tumours, prion disease
   • primary AL amyloidosis
     • light chain of immunoglobulin produced by plasma cell tumours
   • secondary AA amyloidosis- secondary to an inflammatory reaction
   • Renal amyloidosis-
     • gross- pale cortex- white dots in glomeruli
       • stain brown or yellow with iodine
     • dilute sulphuric turns blue/ lilac
     • microscopic-pink homogenous material
     • loss of protein in urine effecting starling forces cuasing oedema in subcut and abdomen
   • hepatic amyloidosis
     • hepatomegaly with risk of rupture
     • looks similar to fatty liver
     • liver gradually fails

8. glycogen storage

   • causes by high corticosteroid exposure
   • microscopic- foamy cytoplasmic vacuoles
   • seen in renal tubules in diabetes
   • liver in prolonged steroid therapy

9. cellular inclusions

   • viral inclusion bodies- viral protein or nucleic acid inside cell
     • location indicates virus types
   • abnormal storage products- hereditary, missing or defective enzymes, affects all tissues, CNS most vulnerable

10. necrosis

    • =death of substantial numbers of cells within or attached to living tissues
    • causes- loss of blood supply, non living agents or living agents
    • LOSS OF BLOOD SUPPLY
      • compression of blood vessels
        • intestinal torsion- venous outflow blocked
          • 5- intestinal barrier compromised- bacterial toxins can enter
        • 1-organs swell due to congestion
        • 2-swelling of organs compresses arterial flow
        • 3-oxygenated blood not delivered to tissues
        • 4-tissue ischaemic necrosis
        • 6- septic shock
      • narrowing of vessel lumen
        • aterosclerosis- progressive fibrotic thickening
        • atherosclerosis- cholesterol in walls
      • blockage of lumen- thrombosis and embolism
        • e.g. hypertrophic cardiomyopathy
    • NON LIVING AGENTS
      • physical agents- burns/ cold/ frostbite/ pressure/ crushing
      • chemical agents- caustic or corrosive agents
    • LIVING AGENTS- infectious agents e.g. black leg dieasee or some toxins producing necrosis in liver
    • appearance of necrotic lesions
      • 3 zones- sphere of necrosis, zone of degeneration and zone of inflammation
      • coagulative necrosis- remains firm
        • gross- firm and dry
        • microscopic-architecture preserved by organelles look ghosted
        • cytoplasm looks ghosted
        • causes- bacterial toxins/ infarction/ foci of viral repliaction
      • liquefactive necrosis- e.g. abcess
        • caused by pyogenic forming organisms
        • cause necrosis- which attracts neutorphils which pathogen kills- relesaing proteolytic enzymes
          • further necrosis
          • histo- lots of neutrophils, pyogenic membrane and fibrous capsule
      • caseous necrosis- like cottage cheese
        • like halfway between two
        • caused by micobacteria- loss of architecture and lots of macrophages
        • stain purple
    • cellular events in necrosis
      • Pyknosis- normal nuclear structure replaced by dense angular chromatin
      • karyorrhexis- nucleus broken into dense bits
      • karyolysis- dissolution of nucleus- only outline of cytoplasm
    • sequale to necrosis
      • surface necrosisi can be shed. if basement membrane is intact it's called erosion. if basement membrane not in tact is called ulceration
      • internal necrosis- small can be replaced by fibrous tissue. large can be replaced by a fibrous tissue- sequestrum
    • OTHER TYPES OF NECROSIS
      • FAT NECROSIS- forms soap saponification when adipocytes die - inflammatory response
      • ENZYMATIC NECROSIS
      • TRAUMATIC NECROSIS
      • DIET RELATED
      • GANGRENE- post necrotic tissue- dead attached to living body
        • wet- life threatening
        • dry- type of mumification- extremities where air flows across - removes fluid

11. pigmentation and mineralisation

    • exogenous pigments
      • inhaled, ingested and iatrogenic
      • carbon- inhaled found in lung parenchyma and macrophages- remain inert black called anthracosis
      • Pneumoconiosis- inhalation and retention of dusts- e.g. sillicosis and asbestos. chronic nflammation cause fibrosis and tumours
      • carotenoids- fat soluble, yellow or orange colour often of plant origin
      • iatrogenic- tattoos, tetracycline
    • ENDOGENOUS PIGMENTS
      • MELANIN
        • protective pigment in skin/ hair/ iris
        • affected by genetics, UV light, chronic damage or copper deficiency
        • hyperpigmentation associated with skin or endocrine disease. hypopigmentation associated with copper deficiency or chronic inflammation
      • BLOOD PIGMENTS
        • haemoglobin- varies with oxidation. carboxyhaemoglobin and methaeglobin
        • hameosiderin- golden colour- complex of protein and iron ACTS AS AN IRON STORE
          • local accumulation in bruises. more diffuse in cases of RBC lysis
          • accumulate in vascular tissues e.g. lungs during heart failure
        • haematin-black
          • acid haematin- Hb binds to formalin histo artifact
          • parasitic- parasite ingest blood and convert Hb to haematin
      • LIPOFUSCIN
        • wear and tear pigment- golden brown accumulate in mature cells harmless
      • BILE PIGMENTS
        • billirubin- yellow remains of heam group once iron is removed- found in macrophages after RBC lysis
        • uncongugated billirubin produced by RBC breakdown. sent fo liver and is conjugated and excreted
        • classification of iacterus
          • pre-hepatic- XS production e.g. haemolysis shows as an incresae in unconjugated billirubin
          • hepatic- some residual conjugated but mostly unconjugated
          • post hepatic- conjugated can't be excretion so increase in conjugated in blood
    • mineralisation
      • calcification
        • calcium salts deposited not in bones or teeth
        • dystrophic- deposits in dead or necrotic tissue
          • underlying calcium metabolism is normal
          • dead cells can't regulate their calcium so it accumulates
        • metastatic calcification
          • in normal tissue
          • disturbed calcium metabolism
          • can be due to hyperparathyroidism
        • calcinosis cutis- accumulate in skin of dogs with cushings
      • crystal formation
        • gout- urate crystals look black- in kidney can block tubules
        • cholesterol- obstruct CSF outlfow can cause hydrocephalus
        • oxalate crystals- antifreeze poisoning in small animals- large animals can be linked to some plants