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pathology - Coggle Diagram

- - - - left = autolysed, centre = normal, right = putrefaction
  - - - hydrogen sulphide - causes a foul smell
      - ferrous sulphide - causes green or black discolouration (pseudomelanosis)
  - - - lasts for 1 to 2 days
    - - process is less effective in heart deteriorating conditions eg. dilate cardiomyopathy
        
        thus will still be blood in left ventricle
    - - normal muscle contraction:
        
        calcium is sequestered in the sarcoplasmic reticulum
        
        an action potential results in calcium being released into the cytoplasm, binding troponin on the actin myofibril which exposes the binding site for myosin and results in contraction of the sarcomere
        
        ATP is required to sequester calcium back in the sarcoplasmic reticulum, resulting in relaxation
      - rigor mortis:
        
        reduced ATP availability after death leads to a build up of calcium in the cytoplasm and consequent muscle contraction that persists as myosin binds to actin
        
        subsequent muscle relaxation is due to enzymatic digestion of actin myosin crosslinks (as cells degenerate permeability increases)
    - - WARM
        
        FLACCID
        
        dead less than three hours
        
        STIFF
        
        dead for 3-8 hours
      - COLD
        
        STIFF
        
        dead for 8-36 hours
        
        FLACCID
        
        dead for more than 36 hours
  - - - upper plasma layer
        
        quite translucent: looks like chicken fat
      - lower red blood cell layer
        
        intensely red and resembles redcurrant jelly
    - - a thrombus is firmly attached to the underlying vascular endothelium, has a white interior, and is layered (due to buildup over time)
  - - - within hours of death haemoglobin released by lysed erythrocytes stains blood vessel walls and adjacent tissues
      - best appreciated on surface vessels of organs such as intestine
      - foetuses which are dead for a few days prior to expulsion are usually diffusely red with imbibition
      - blood in RIGHT VENTRICLE diffusely stains the endocardium (LV expels blood)
      - cases with haemolytic crisis = staining of tissues early after death
      - MOST COMMON OBSCURER OF LESIONS IN POST-MORTEM EXAMINATION - can get hard to appreciate blood pooling/haemorrhage v quickly
      - progressive discolouration of tissues after death due to haemoglobin release from RBC breakdown
    - - starts WITHIN HOURS OF DEATH
      - bile in the call bladder penetrates the wall and stains adjacent tissue yellowish and then greenish brown
      - stain involved LOCAL liver, omentum, GI tract
      - should not be confused with icterus which is diffuse, yellowish discolouration of normally pale tissues eg. mucus membranes, sclera, subcutis in non-pigmented skins during life - typically much more widespread
  - - - abdominal viscera may be pale in comparison to thoracic viscera or the musculature of the hind limbs
      - gas rises: distended loops may be pale and lower loops hypo statically congested (not to be confused with inflammation_
    - - important to distinguish this from ante-mortem rupture of the intestine
        
        blood at tear (local pathology) & fibrin deposits indicated peritonitis (typically systemic)
        
        visible haemorrhage antemortem at rupture site
    - - open along the midline rather than at the highest point or use a needle to release pressure
  - - - whitish fly larvae in the mouth and other orifices - eggs deposited after death and larvae appearing within hours
      - may occur before death in weak or debilitated animals
- - - - GROSS
        
        initial cell type influences type and appearance of cancer
      - HISTOLOGICAL
        
        proliferation of a single cell type
    - - HER-2/neu
        
        encodes for a cell surface receptor that can stimulate cell division
        
        amplified in up to 30% of human breast cancers
      - RAS
        
        gene products are involved in kinase signalling pathways that ultimately control transcription of genes, regulating cell growth and differentiation
      - MYC
        
        FeLV/FIV
        
        the Myc protein is a transcription factor and controls expression of several genes
      - SRC
        
        the Src protein is a tyrosine kinase which regulates cell activity
        
        rous sarcoma virus
      - hTERT
        
        codes for an enzyme (telomerase) that maintains chromosome ends
    - - p53
        
        a transcription factor that regulates cell division and cell death
      - Rb (retinoblastoma)
        
        alters the activity of transcription factors and therefore controls cell division
      - APC (anaphase promotic complex)
        
        controls the availability of a transcription factor
    - - several types of mutation can lead to altered protein function
        
        point mutation/single base pair mutation
        
        frame shift mutations
        
        insertions
        
        deletions
        
        duplications
        
        inversions
        
        structural chromosomal changes
        
        translocation
        
        gene copy number increases or decreases
      - somatic vs germline
        
        somatic mutations in 90% of cases
        
        seen in any body cell apart from sperm/ovum
        
        restricted to individual cells and progeny
        
        germline mutations identified in 20% human cases
        
        these are seen in cells that develop into sperm or ovum and can be passed onto offspring
        
        seen as early age onset
    - - neurofibromatosis of haired skin and mesentery and adrenal ganglioneuroma in an 18 day old puppy
        
        spontaneous germline mutations in the NF1 tumour suppressor gene leads to development of neurofibromatosis type 1 (NF1)
        
        tumour suppressor gene NF1 encodes neurofibromin, inhibits the cell cycle by inhibiting the RAS-mitogen-activated protein kinase (RAS-MAPK) pathway
    - - epigenetic mechanisms regulate gene expression without causing structural changes to the genome and play a role in malignant transformation
      - epigenetic transformation may explain tumours associated with inflammation or foreign material but no clear pattern of mutation
      - eg. helicobacter pylori
        
        associated with inflammation & stomach ulcers
        
        increased risk of stomach ulcers
      - DNA methylation
        
        silence, diminish or increase gene expression
        
        affects tumour suppressor genes in many human cancers
      - histone acetylation
        
        DNA wind around histone protiens
        
        gene expression affected by loosening/tightening binding of DNA strands to histone protens
      - microRNA expression
        
        microRNAs are small non-transcribed RNA molecules that bind to mRNA and cause postranscriptional silencing
        
        increased expression targets tumour suppressor genes, reduced expression leads to oncogene overexpression
  - - - INITIATION
        
        INITIATED CELL
        
        PROMOTION
        
        PRE-NEOPLASTIC LESION OF BENIGN TUMOUR
        
        PROGRESSION
        
        MALIGNANT TUMOUR
        
        genetic/irreversible, non-genetic/reversible
        
        4 more items...
        
        non-genetic, reversible
        
        initiated cells exposed to certain stimuli (promoting agents/promoters eg. immune system depressors, hormones), which alter gene expression and create an environment which drives proliferation
        
        initiated cells grow more rapidly and in less controlled way than normal cells
        
        may lead to development of preneoplastic lesion or benign tumour
        
        promotors are non mutagenic so their effects can be reversible
        
        genetic, irreversible
        
        introduction of irreversible genetic change into cells by actions of mutagenic initiator eg. chemical or physical carcinogens that damage DNA
        
        initiated cells appear morphologically normal, may remain quiescent for years
        
        mutations give them a growth advantage so they respond more quickly/vigorously to mitogenic signals or are resistant to apoptosis-inducing stimuli
    - - Normal Epithelium
        
        APC mutation - tumour suppressor gene loss
        
        dysplastic aberrant cryptic foci
        
        COX-2 over expression - angiogenesis
        
        early adenoma
        
        k-ras mutation - oncogene activation
        
        1 more item...
  - - - accumulation of genetic damage
      - decreased immune function
      - lag between transformation and clinically detectable tumour (slow growth)
    - - chemicals
      - radiation
        
        all forms of radiation able to initiate and promote
        
        mutations caused by direct (radiant energy) or indirect (free radicals) effects
        
        eg.
        
        UV rays esp. UVB
        
        ionising radition
        
        radioisotopes
        
        radiographs
        
        radiation therapy (shorter wavelengths)
        
        gamma
        
        x rays
        
        UV
        
        clinical examples
        
        UV
        
        non pigmented areas lack melanin to protect nucleus
        
        cat ears
        
        hereford cattle eyelids
        
        SSC
      - hormones
        
        steroid hormones
        
        growth hormones
      - bacteria/parasites
        
        eg. spirocerca sp.
      - viruses
  - - - cell morphology
      - biological behaviour
    - - uniform cellular appearances
        
        benign round cell tumour
        
        dog skin
        
        cutaneous histiocytoma (macrophages)
        
        will regress on its own
        
        growssly appears same as mast cell tumour
        
        benign smooth muscle cell tumour
        
        dog intestine
        
        leiomyoma
        
        uterus
        
        bladder
      - grow by expansion
      - may have rim of connective tissue (capsule)
      - do not penetrate capsule or surrounding tissues
      - shell out easily at surgery
      - tend to grow by expansion and compression
        
        form capsure
        
        discrete
      - benign tumour on skin surface; no invasion into underlying tissues
      - SUMMARY
        
        resemble normal tissue/cell
        
        uniform cell and nuclear size and shape
        
        grow by expansion
        
        often encapsulated
        
        often slow growth
        
        usually low numbers of mitoses
        
        do not spread
        
        may ulcerate on body surface, may cause pressure on other organs
        
        endocrine tumours may or may not be ufnctional
        
        usually amenable to surgery
    - - variable cellular and nuclear size and shape
      - giant nucleolus
      - multinucleate tumour cells
      - bizarre mitotic figures present in malignant neoplasm
        
        weird big hyper chromatic chromatin
      - invasive and infiltrative
      - lack defined capsule or border
      - surgery requires removal of wide margin of surrounding tissue to ensure complete removal
      - may grow by local invasion
        
        no capsule
        
        non discrete
      - malignant tumour invading through skeletal muscle into adjacent tissues
        
        effecting normal tissues
      - SUMMARY
        
        may look different to normal tissue/cell
        
        often variable cell and nuclear size/shape/number
        
        grow by invasion
        
        usually no capsule
        
        often fast growth
        
        often high number of mitoses
        
        spread by local invasion or metastasis
        
        necrosis centrally, ulcerate
        
        may be functional - secretions may be inappropriate (paraneoplastic effects)
        
        often hard to completely remove surgically
  - - - epithelial
        
        derived mostly from ectoderm and endoderm germ layers
        
        cells cover or line the surfaces of the body or organs
        
        apical basal polarity, cell to cell tight junctions
        
        high density with little intercellular substance
        
        separated from CT by a basement membrane
        
        neoplastic keratinocytes
        
        squamous cell carcinoma
        
        nests, packets and cords of polygonal shaped cells
      - mesenchymal
        
        connective tissue
        
        bone
        
        cartilage
        
        blood vessels
        
        haematopoietic
        
        lymphoid and haematopoetic tumours
        
        round cell
        
        derived from the mesoderm
        
        diff dx for round cell cutaneous tumours
        
        mast cell tumour
        
        histiocytoma
        
        plasmacytoma
        
        lymphoma
        
        rou pebbles on a beach, sheets of round cells
        
        derived from mesoderm
        
        no polarity, loosely attached to each otehr
        
        produce and are separated by extrcellular matrix
        
        streaming, brush strokes, swirls
        
        fibrosarcoma
    - - benign
        
        oma = benign neoplasm
        
        Adeno = glandular tumour
        
        eg.
        
        haemangioma - benign tumour of vascular endothelium
      - malignant
        
        carcinoma = malignant epithelial origin
        
        sarcoma = malignant mesenchymal origin
        
        eg.
        
        haemangiosarcoma - malignant tumour of vascular endothelium
    - - lymphoma, lymphosarcoma
        
        used for malignant tumours of lymphoid tissue
        
        leukaemia - used when malignant lymphoid cells are circulating in the blood
      - myeloma, plasma cell tumour or plasmacytome
        
        all refer to plasma cell tumours
      - melanoma, melanocytoma
        
        refer to tumours of melanocytes (pigment producing cells)
        
        can also be melanotic or melanotic
  - - - more haphazard, thrombotic and necrotic in malignant tumours
    - - metaobolism by tumour cells
      - sustained growth
      - metastasis of malignant tumours
    - - tumour lymphangiogenesis similar - essential for lymphatic spread of tumurs
      - density of vessels = ?prognostic indicator
    - - often accompanied by patches of necrosis and haemorrhage - usually associated with MALIGNANCY due to outgrowth of blood supply, poorly formed vessels and compression of vessels
  - - - primary tumour
        
        detachment, penetrate basement membrane, enter ECM
        
        loosen intercellular tight junctions eg. cadherin
        
        form cell-ECM connections eg. integrins
        
        degrade BM and ECM by producing proteases
        
        adhesion to vessel wall
        
        invasion of vessel
        
        transport of micrometastasis
        
        evasion of host defences & platelet clumping
        
        1 more item...
    - - spread of primary tumour to another site in the body
    - - hepatopahty
      - bone pain and fractures
      - lymphadenopathy
      - ascites/pleural/pericardial effusion
    - - INTRAVASCULAR
        
        blood (harmatogenous)
        
        follow venous drainage from primary site - tumour embolus
        
        must successfully complete metastatic cascade
        
        organ preferential metastatic sites
        
        bone: mammary, prostate, ovary, lung
        
        brain: melanoma
        
        lymphatic
        
        lymphatics offer little resistance (thin walls, low pressure)
        
        entrap in first lymph node or "skip"
        
        not all enlarged lymph nodes contain mets
      - SEROSAL SPREAD or transcoelomic spread
        
        often occurs on coelomic surfaces
        
        peritoneum
        
        pleura
        
        pericardial sac
        
        neoplastic cells can be detected fluid aspirates
        
        eg. nodules from pancreatic adenocarcinoma spreading throughout abdomen omentum
      - INTRA ORGAN SEEDING
        
        local seeding
        
        via airways (lungs)
        
        local blood/lymph drainage (liver, kidneys)
      - LOCAL INVASION
  - - - replacement of functioning cells
      - compression
      - invasion
      - organ rupture
      - embolus formation (infarction)
      - ulceration
      - haemorrhage
    - - systemic complications of neoplasia that are remote from the primary tumour
      - importance
        
        may be the reason the animal was bought to the vet, therefore diagnostic aid to cancer
        
        can be more injurious than the malignancy
      - pathogenesis
        
        due to a product produced by the tumour cells
        
        hormones
        
        hormone precursors
        
        enzymes
        
        cytokines
        
        e.g
        
        an endocrine tumour
        
        ectopic production of hormone like substances by tumour cells that are not an endocrine organ
        
        due to antibodies produced against foreign tumour cells targeting other tissues
      - affect different systems
        
        blood
        
        anaemia
        
        thrombocytopenia
        
        DIC
        
        skeleton
        
        hypertrophic osteopathy
        
        symmetrical lameness and extensive periostea new bone, limbs
        
        associated with space-occupying thoracic lesions
        
        pulmonary lesion lead to reflex vasomotor changes, mediated by the vagus nerve, and get increase blood flow to the extremities
        
        neurologic clinical signs
        
        myasthenia gravis: associated with thymoma
        
        blocks neuromuscular synapses (?immune mediated)
        
        clinical signs
        
        weakness
        
        dysphagia (secondary inhalation pneumonia)
        
        GIT clinical signs
        
        Zollinger Ellison syndrome
        
        islet cell tumour int eh pancreas produces gastrin - releases histamine into blood stream, which binds to receptors on the parietal cells int he stomach and increases HCL rpoduction
        
        GI ulceration
        
        abdominal pain
        
        vomiting
- - - - viruses
        
        eg. EHV-1 (aetiology)
        
        infection causes abortion (excessive fluid in chest of aborted foetus) - pathophysiology
        
        virus causes necrosis with intranuclear inclusion bodies in multiple organs eg. liver - lesion
      - bacteria
        
        eg. salmonellosis (aetiology)
        
        causes intestinal haemorrhage - pathophysiology
        
        bacterial colonisation of intestinal mucosa results in haemorrhage and necrosis
        
        differing microscopic appearance
        
        consider gross clinical changes that inform differential diagnosis (intestinal haemorrhage) and then send off samples to observe microscopically (mucosal colonisation)
      - fungi
      - parasites
        
        eg. Dictyocaulus viviparous (aetiology)
        
        lungworm (husk) affecting calf
        
        areas of pneumonia anteroventrally as tends to gravitate
        
        lungworm larvae in airways are easily visible
    - - trauma
        
        eg. intestinal rupture
        
        perforation of equine intestine
        
        peritonitis caused by leakage of gut contents
      - pressure
      - heat
      - cold
      - radiation
    - - toxic organic and inorganic substances
        
        eg. yew poisoning in cattle
        
        sudden death in cattle due to yew on the pasture
        
        important to visit area of incident especially with large animal poisoning - observation is key
      - toxins produced by infectious agents
    - - deficiencies of vitamins and trace elements
        
        eg. vitamin E/selenium deficience
        
        pale streaks in muscle indicate degeneration and necrosis: white muscle disease
        
        streaks of white - dead
        
        pale pink - degenerating
        
        microscopic examination of muscle confirms degeneration and necrosis
      - excess vitamins and trace elements
      - typically issue with a single specific element rather than whole body deficiency
    - - range of lethal and sublethal defections
      - eg. myofibrillar hypoplasia
        
        newborn piglet unable to stand (NCWL)
        
        small poorly developed skeletal muscle fibres
        
        pink should fill the whole field
        
        gene therapy & regenerative medicine may help
  - - - acute - sudden onset and short duration
        
        outcome
        
        causes death of animal
        
        resolves due to host defence or clinical therapy
        
        becomes chronic disease
        
        eg. bovine respiratory syncytial virus invection in a calf
        
        acute pneumonia caused by respiratory syncytial virus
        
        syncitial cells in a section of the lung
      - chronic - of insidious onset and protracted course
        
        outcome
        
        progressively destroys tissue compromising its function and endangering life
        
        course is halted and tissue repairs by scarring
        
        eg. Rhodococcus equi infection in a foal
        
        lungs of a foal with chronic pneumonia
        
        note the granuloma, typical of chronic inflammation on the cut surface
        
        fibrous capsule formed around granuloma
    - - animal related
        
        age
        
        nutrition
        
        immune status
      - agent related
        
        dose
        
        virulence
        
        single infection
        
        mixed infection
      - environment related
        
        overcrowding
        
        management
        
        temperature extremes
      - focus on all three factors, not just the animal
  - - - the live animal
      - tissues surgically removed from the live animal
      - in animals soon after death (necropsy, post mortem examination)
    - - major changes accruing post mortem are due mainly to autolysis and putrefaction
    - - bacillary necrosis - gross
      - bacillary necrosis - microscopic
  - - - study of blood cells and chemical components
      - haematology
        
        study of number and type of circulating red and white blood cells
        
        increase red cell numbers: erythrocytosis
        
        decreased red cell numbers: anaemia
        
        increased white cell numbers: leucocytosis
        
        decreased white cell numbers: leucopenia
      - biochemistry (clinical chemistry)
        
        study of chemical components of blood and body fluids
        
        eg. urine examination for
        
        renal function
        
        urinary infections
        
        renal protein loss
        
        metabolic disease (eg. diabetes)
    - - cells in smears, aspirates and fluids
      - examination of cells in body cavities (eg. cerebrospinal fluid or synovial fluid) or aspirated from tissues (eg. tumours, abscesses or cysts)
      - number and type of cell present in fluid indicates underlying process
    - - gross changes in the dead body
      - post mortem examination
    - - microscopic examination of tissues selected from the dead body after necropsy, or biopsy/excision of lesions in the living animal
        
        biopsy examination eg. gross and microscopic appearance of a histiocytoma (common benign tumour in young dogs)
    - - microscopic visualisation of enzymatic activity in tissues
      - use of enzymes to detect different types of tissue - for example different muscle fobre types by ATPase staining of skeletal muscle
    - - detection of specific antibodies or antigens in tissues or fluids (eg. to show prior exposure to an infectious agent)
      - immunohistochemistry
        
        use of labelled antibodies to detect cell markers (eg. in cancer diagnosis) or infectious agents in tissues
        
        example is CD3 immunohistochemistry to diagnose a T-cell tumour
    - - fine detail of the surfaces or internal structures of cells
      - method less used now - detects internal structure of cells or novel infectious agents
    - - isolation and identification of pathogenic bacteria/viruses/parasites
      - culture or PCR for infectious agents
        
        traditional culture techniques largely been superseded by PCR for reasons of speed, sensitivity and specificty
        
        culture is still used in cases where PCR assays are not available or drug sensitivity data are required
    - - analysis of tissues for particular poisons and toxins
      - a good history and environmental assessment are very important in toxicology to narrow down possible toxins for testing
      - common plant poison in the UK is ragweed - grazing horses and cattle
        
        chronic hepatic damage
- - - - fibrosis
      - shrunken
      - pale
    - - can follow on from an unresolved acute inflammation
      - can be chronic from the outset
      - composed of cellular infiltration and proliferation of local connective tissue
      - more complex than the stepwise phases of acute inflammation
    - - lymphocytes
        
        formed in:
        
        bone marow
        
        spleen
        
        thymus
        
        lymph nodes
        
        mucosal suface associated lymph follicles
        
        Peters patch in intestine
        
        tonsils of the oropharynx
        
        circulate between the blood, tissues and lymphatic system
        
        life span up to 200 days
        
        round cells with a densely staining nucleus and a thin, often indistinct, rim of cytoplasm
        
        various types similar in appearance but differing in function - distinguish by immunohistochemistry
        
        T cells: CD3
        
        B cells: CD79a
      - plasma cells
        
        derived from B-lymphocytes at the area of tissue damage
        
        arrive in efferent lymph from sites of differentiation in lymph nodes
        
        presence of plasma cells in a tissue indicates the body is producing an antibody response against an antigen
        
        round to oval shaped cells with an eccentric round nucleus and abundant plum/purple cytoplasm
        
        nucleus pushed to periphery at one pole of the cell
      - macrophages
        
        significantly larger than others
        
        large round cells with central to eccentric round nucleus and abundant clear, often vacuolated (foamy) cytoplasm
        
        normally present in tissues as fixed histiocytes
        
        eg. sentinel macrophages in the lung
        
        in inflammation are mostly derived from circulating monocytes which leave blood vessels and enter tissue
        
        FUNCTIONS OF MACROPHAGES
        
        phagocytosis
        
        antigen presentation
        
        stimulation of fibroplasia (immature) and fibrosis (mature) (tissue remodelling)
        
        MACROPHAGE ACCUMULATION IN TISSUES
        
        macrophages accumulate due to:
        
        inability to lyse irritants
        
        foreign material
        
        eg. fragments of glass
        
        antigen-antibody complexes forming around infectious agents forming 'tissue grains'
        
        can form and look like little grains of sand within pleural effusion
        
        survival of infectious agents within macrophages
        
        eg. acid-fast bacilli
        
        common of tuberculosis mycobacterium
        
        MACROPHAGE SUBTYPES
        
        variations in macrophage appearance in microscopic sections
        
        epithelioid cells
        
        look like squamous epithelial cells with a pink cytoplasm and indistinct borders
        
        my be binucleate
        
        foamy
        
        primary secretory rather than phagocytic
        
        giant cells
        
        multinucleate cells formed by the fusion of macrophages or epithelioid cells
        
        seen in tissues in association with stable foreign material or intracellular bacteria eg. Mycobacterium spp.
        
        macrophages have a key role in repair and regulation of COLLAGEN PRODUCTION
        
        cytokines (increased collagen synthesis)
        
        IL-1
        
        IL-4
        
        IL-10
        
        IL-13
        
        GM-CSF
        
        growth factors (increased fibroblast proliferation)
        
        polyamines
        
        FGF
        
        PDGF
        
        TIMPs
        
        decreased matrix metalloproteinase activity
      - cells of repair
        
        vascular endothelium
        
        in conjunction with fibroplasia there is a proliferation of the vascular endothelium into the organising tissue (granulation tissue) - living cells
        
        fibroblasts
        
        derived from local connective tissue and involved in the organisation of damaged tissue (fibroplasia) (collagen)
    - - an important type of chronic inflammation usually caused by organisms of low virulence but great persistence in the tissues or by implanted foreign bodies
      - macrophage is the main effector cell
      - similar to abscess in acute
      - MICROSCOPIC STRUCTURE
        
        central core containing agent or irritant
        
        surrounding chronic inflammatory cells
        
        macrophages (often as epithelioid cells), lymphocytes and plasma cells
        
        eosinophils in parasitic granulomas
        
        necrosis in mycobacterial and fungal granumolas
        
        calcification (dystrophic) in mycobacterial granulomas in some species
        
        outer fibrous capsule
      - EXAMPLES
        
        eg. bacteria Actinomyces bovis (lumpy jaw)
        
        bacterial colonies ('tissue grains')
        
        gross deformity of mandible
        
        animal produces a robust antibody response - accumulation of macrophages is hindering further immune cells
        
        bacteria Mycobacterium spp.
        
        large granuloma in bovine lung (M. bovis)
        
        acid fast bacilli in giant cell of a bird (M. avium)
        
        parasites
        
        Muellerius capillaris: ovine lung
        
        Filaroides osleri: canine trachea
    - - Removal of necrotic debris
        
        ingrowth of immature blood vessels (granulation tissue)
        
        production of immature scar tissue (fibroplasia)
        
        production of mature scar tissue (fibrosis)
        
        mature scar is as strong or stronger than the original tissue
        
        replaces granulation tissue
        
        GRANULATION TISSUE FORMATION
        
        vascular connective tissue
        
        capillary loops
        
        fibroblasts - collagen production
        
        leukocytes - granulocytes & macrophages
        
        extremely resistant to infection
        
        supports migration of epithelium
        
        its contraction reduces the amount of tissue to be replaced
        
        forms at sites of skin injury if large areas of epithelium have been lost
        
        forms the lining of sinus tracts discharging from deeper lesions
        
        the most frequent example in domestic animals is the formation of excessive granulation tissue on the legs of horses with poorly healing wounds - 'proud flesh'
        
        tissue structure
        
        meshwork of immature blood vessels, fibroblasts, small amounts of collagen
      - FACTORS AFFECTING HEALING
        
        the species affected
        
        eg. peritonitis in cattle is often focal and chronic whereas peritonitis in horses is often diffuse and rapidly fatal (eg. intestinal perforation)
        
        the age of the animal
        
        healing is generally more effective in young vs elderly animals
        
        the nature of the tissue damaged
        
        highly specialised tissue rarely repairs successfully unless the injury was mild (eg. fibrocartilaginous embolism in the spinal cord of dogs)
        
        the extent of tissue damage
        
        if there is substantial fibrosis in the tissue, progressive destruction of the tissue continues due to further injury to adjacent normal tissue from the fibrous tissue as it matures and contracts
        
        the liver in cirrhosis (end stage)
        
        the kidney in chronic renal disease
    - - REPAIR
        
        the process of replacement of damaged tissue by fibrous scar tissue (fibrosis)
        
        the damaged tissue is replaced by granulation tissue and then by fibrous scar tissue
        
        the scar tissue does not retain the functional characteristics of the tissue that it has replaced
        
        the functional impact on the animal depends on how much tissue has been replaced
      - REGENERATION
        
        the process of replacement of damaged tissue by normal tissue of the same type
        
        the functional status of the tissue is restored
      - TISSUES ARE DIVIDED INTO THREE CATEGORIES ACCORDING TO THEIR ABILITY TO REGENERATE NORMAL STRUCTURE - tissues with a greater capacity to regenerate are more likely to regain normal function after damage
        
        labile
        
        constantly replenishes its tissue cells throughout life
        
        skin and mucous membranes which normally desquamate their outer layer of cells during life
        
        bone marrow and fat are other examples
        
        stable
        
        able to regenerate in response to damage
        
        liver
        
        some endocrine glands
        
        renal tubule epithelium
        
        or able to respond to an increased demand on function
        
        skeletal muscle
        
        smooth muscle
        
        permanent
        
        poor or no regenerative capacity: highly specialised tissues whose cells generally have only one function
        
        neuronal cell bodies in the CNS, the retina of the eye, and the cells responsible for hearing in the ear
        
        axons in the PNS, when severed, can regenerate to a limited extend
        
        cardiac muscle myofibres have very poor regenerative capacity, and undergo repair by fibrosis or fat replacement
      - STAGES IN SKIN WOULD HEALING:
        
        PRIMARY UNION = HEALING BY FIRST INTENTION
        
        haemostasis
        
        blood escapes from damaged blood vessels and fills the defect
        
        platelet degranulation > mediator release
        
        fibrin clot loosely binds the edges and dries to form a surface scab
        
        inflammation
        
        acute inflammation develops and within 24h adds exudate to the site
        
        inflammatory cells produce enzymes which debit to degrade the clot and act as scavengers to remove debris
        
        macrophage products promote repair
        
        fibrin & fibronectin network provides stability and framework for cell migration
        
        repair
        
        epithelial cells start to regenerate and bridge the gap within 48h
        
        blood vessels regrow and may form a small amount of granulation tissue
        
        very rapid in skin
        
        consolidation/reconstruction
        
        2 more items...
        
        HEALING BY SECOND INTENTION
        
        much more angiogenesis
        
        more collagen
        
        more distortion
        
        puckering
        
        typically a wider wound/gap
  - - - death
      - resolve by regeneration in association with host defence mechanisms (which may be assisted by therapeutic measures)
      - undergo repair by fibrosis - scarring
      - become chronic (goes through a subacute phase first), depending upon the persistence of the agent and the amount of damage
    - - dark red
      - swollen
      - more blood
      - fluid from cut surfaces
    - - Stage 1: Vascular phase
        
        Initial phase - transient (secs)
        
        arteriole constriction (white line) - reflex vasoconstriction
        
        smooth muscle response
        
        unlikely to see it
        
        Hyperaemia = (mins - days)
        
        arteriole and capillary dilation
        
        key chemical mediators arrested prostaglandins, endothelia and nitric oxide
        
        precapillary sphincters open to divert blood to the tissue
        
        redness
        
        heat
        
        blood cells are slower due to fluid dynamics
        
        can infarct more
      - Stage 2: Exudative Phase
        
        increased vascular permeability is due to endothelial cell contraction
        
        endothelial cell contraction is caused by histamine released by mast cells
        
        also direct endothelial injury
        
        physical damage
        
        toxic agents
        
        infection
        
        enzymes
        
        oxygen free radicals
        
        result - escape (exudation) of protein rich fluid from blood into surrounding tissue
        
        contents of fluid exudate
        
        water and electrolytes
        
        plasma proteins
        
        albumin
        
        globulin
        
        fibrinogen
        
        (low-> high molecular weight)
        
        red blood cells
        
        platelets
      - Stage 3: Migration of Leukocytes
        
        margination/pavementing
        
        altered blood flow & loss of axial stream
        
        expression of adhesion molecules (eg. selecting, integrins)
        
        chemotaxis
        
        neutrophils move along a chemotactic gradient at ~2mm per hour (macrophages are slightly slower)
        
        chemotaxis that attract & activate keukocytes
        
        bacterial products eg. endotoxin
        
        fibrin degradation products
        
        complement derived factors
        
        cytokines esp. lymphokines
        
        tissue breakdown products
        
        emigration via intercellular junctions
        
        motile cells force an opening
        
        basement membrane is breached
    - - neutrophils
        
        formed in the bone marrow
        
        production time 7 days - half life in blood 6 hours
        
        get replaced twice a day
        
        once they enter the tissues generally do not return to the blood
        
        most are lost through the mucous membranes of the body
        
        gut
        
        urinary
        
        respiratory tract
        
        have multi lobed nuclei and fine cytoplasmic granules
        
        FUNCTIONS
        
        phagocytosis of microorganisms or foreign material and fusion of phagosome with lysosomes to kill or degrade material
        
        secretion and/or release of granules into exudate to enhance acute inflammatory response
        
        acts on a chemotactic gradient
        
        as neutrophils leave circulation they recruit more to come with them
        
        RECRUITMENT
        
        marginate in small veins (venules) & capillaries
        
        loosely adhere to endothelium and roll along inner blood vessel wall (mediated by selectins)
        
        at junction between endothelial cells, firmly adhere and emigrate from blood vessel into tissue (mediated by integrins)
        
        migrate to sit of damage along a chemotactic gradietn
        
        1 more item...
      - eosinophils
        
        formed in the bone marrow, have a similar life span to neutrophils
        
        when there are many eosinophils in a tissue, as with parasitic conditions, they impart a greenish colour to the tissue
        
        have bilobed nuclei and distinct granules in the cytoplasm
        
        are prominent in parasitic infections, and local allergic reactions [IgE]
      - mast cells
        
        heavily granulated mononuclear cells found in tissues
        
        tissue lifespan 4-12 weeks depending on location
        
        degranulate in tissue injury, releasing:
        
        histamine
        
        heparin
        
        5-hydroxytryptamine (serotonin)
        
        chemical mediators of vasodilation, chemotaxis and pain
        
        critical in initiation of ACUTE RESPONSE
      - basophils
        
        also formed in the bone marrow
        
        multilobed nucleated cells with large bluish granules in the cytoplasm
        
        granules similar to those of both neutrophils and mast cells
        
        important in IgE mediated injury to tissues (allergic reaction)
    - - pyrogens - act on the temperature control centres in the hypothalamus of the brain to raise body temperature
      - neutrophils
        
        prime source when they begin to phagocytose, also eosinophils and macrophages
      - gram-negative organisms
        
        their cell walls contain pyrogens
      - damaged tissue cells
        
        necrosis releases pyrogens
      - antigen-antibody complexes
        
        may release pyrogens
      - tymours
        
        may release pyrogens particularly those which have metastasised (spread throughout the body) - also the pyrexia caused by the central necrosis in such tumours
    - - momentary vasoconstriction of the blood vessels in affected area
        
        dilation of blood vessels
        
        exudation of fluid, rich in protein, into the tissues (effusion)
        
        margination of leukocytes
        
        emigration of leukocytes through the altered endothelium
        
        induction of increased temperature
        
        functions of an inflammatory effusion
        
        dilutes the agent
        
        contains antibodies - which attack or opsonise the agent and facilitate phagocytosis by neutrophils and macrophages
        
        may contain fibrin which immobilises the agent and provides a matrix for migration of inflammatory cells
        
        contains chemotaxis that attract more inflammatory cells to the site
        
        washes away the agent - if on a surface -- eg. skin and alimentary tract
        
        brings the agent via the lymphatic vessels to the local lymph nodes - for further processing or antigen presentation
      - mostly induced by the actions of cytokines, chemokine and other chemical mediators
    - - 1. serous
        
        due to mild vascular injury in an organ or in vessels underlying a surface
        
        a clear to cloudy watery fluid with little protein present
        
        vesicles of the skin produce a serous fluid; many inflammations in joints are serous
        
        sequel - resolves when the irritant is overcome, or may progress to a more serious reaction
      - catarrhal
        
        mild form occurring on mucus membranes with goblet cells and/or mucus glands
        
        varies from watery to gelatinous in consistency and cloudy to pinkish in colour
        
        essentially a shedding of epithelium, mucus, neutrophils, some RBCs, and flecks of fibrin
        
        common in mild forms of rhinitis, tracheitis, bronchitis, gastritis and enteritis
        
        sequel - resolves when the irritant is overcome, or may progress to a more serious reaction
      - 3. fibrinous
        
        due to more severe endothelial injury resulting in the escape of fibrinogen from the blood and conversion to fibrin
        
        Is a yellowish coagulum on the surface of a tissue or within its substance
        
        is common in lungs and on serious surfaces (eg. thoracic, pericardial and peritoneal)
        
        in hollow organs, it may coagulate within the lumen, forming a cast
        
        it will peel off from the underlying tissue
        
        sequel - fibrinous exudates may also resolve if the fibrin is digested by macrophages
        
        in pleural, pericardial and peritoneal cavities, organisation of the fibrin into fibrous tissue may occur producing adhesions between the visceral and parietal surfaces
        
        acute fibrinous pneumonia - bovine lung
        
        interstitial pulmonary fibrosis with continuing inflammation and abscess formation
      - diphtheritic
        
        a more severe form of fibrinous exudate in which there is considerable necrosis of underlying tissues
        
        firmly adherent to the underlying tissue: attempts at removal cause tearing of this tissue
        
        commonly seen with internal surface fungal infections
        
        nose of dog
        
        guttural pouch of horse
        
        fungal toxins penetrate underlying tissue causing coagulative necrosis
        
        can be very haemorrhagic
        
        sequel - repairs by scar formation - regeneration unlikely
      - haemorrhagic
        
        a severe acute to parachute inflammation in which haemorrhage is the main component
        
        seen in the lymph nodes, lungs and intestine in severe inflammation
        
        sometimes occurring in all tissues
        
        sequel
        
        if widespread, is most commonly associated with acute deaths eg. acute viral, bacterial or toxic diseases
        
        if strictly localised eg. bruising, then it may repair
      - purulent
        
        where pus (an admixture of dead and dying neutrophils with necrotic cells and a pyogenic agent) is the predominant feature
        
        proteolytic enzymes released by the dying neutrophils lyse tissue cells producing a fluid
        
        colour varies - white, yellow, green, brown - depending upon the agent
        
        sequel - the resolution of abscesses depends upon their location
        
        if near to a surface, will rupture onto it
        
        beneficial in the skin where it discharges to the exterior with or without the pyogenic organism
        
        detrimental if rupture is into a body cavity
        
        in deeper tissues, there is extensive fibrous capsule formation, the fluid becomes inspissated due to withdrawal of water content, macrophages digest the necrotic remains and fibrous tissue organises the interior, the end result being a fibrous scar
    - - LOCAL TISSUE SWELLING
        
        laryngeal oedema in acude laryngitis
      - LOCAL TISSUE DAMAGE due to inflammatory cells or their products
        
        eg. in recurrent airway obstruction in horses alveolar walls are damaged by proteases from neutrophils
        
        eventually leads to emphysema
  - - - INFECTIOUS ARTHRITIS
        
        infection is the main cause of arthritis in livestock (often arising from navel)
        
        inflammation may arrive in the joint via:
        
        the bloodstream
        
        spread from bone
        
        spread from periarticular tissues
        
        direct penetration [including poor aseptic sampling technique, or trauma]
        
        acute arthritis secondary to infection
        
        arrows point to reddened synovial membrane (inflamed)
        
        as the articular cartilage is avascular it does not become inflamed
        
        joint aspirate from a case of acute arthritis caused by infection
        
        macrophages
        
        neutrophils
        
        free and phagocytose bacteria
      - NON INFECTIOUS ARTHRITIS
        
        degenerative joint disease is an immune-mediated process important in adult animals (eg. dogs)
        
        case of degenerative joint disease - thickening and mottling of the synovial membrane
        
        prominent cells typically lymphocytes and plasma cells
    - - BRONCHOPNEUMONIA
        
        Caused by airborne agents (infectious, especially bacteria)
        
        as inhaled infectious agents gravitate to the ventral parts of the lungs, inflammation is most severe in the cranio-ventral portions of the lobes
        
        apical, cardiac and cranial portions of the diaphragmatic lobes
        
        mainly bacterial eg. Mannheimia haemolytic in cattle
        
        photomicrograph of bronchopneumonia
        
        inflammation is centred on the airways
        
        airway in the centre is plugged by inflammatory cells, mucus and protein
      - CUFFING PNEUMONIA
        
        subtype of chronic bronchopneumonia where the predominant change is peribronchal and peribronchiolar cuffing with lymphocytes
        
        can result in the formation of lymphoid follicles, sometimes large enough to cause partial occlusion of the airways
        
        Mycoplasma infections are often involved
      - INTERSTITIAL PNEUMONIA
        
        caused by haematogenous agents
        
        infectious agents (especially viruses) and toxins arriving in the bloodstream cause interstitial pneumonia
        
        this type of pneumonia is diffuse or multifocal
        
        interstitial pneumonia caused by distemper virus infection in a dog (arrows indicate interlobular oedema)
        
        rather than centred on airways, inflammation is centred on the alveolar septa, which becomes progressively thickened, hampering blood gas exchange
    - - GASTROENTERITIS/COLITIS
        
        infections are generally controlled by profuse GALT, the continous movement of ingest and various secreted antimicrobial peptides eg. beta-defensins
        
        in mild infections, the inflammation is usually catarrhal, particularly in the large intestine where there are numerous goblet cells
        
        catarrhal inflammation affecting the colon, with abundant surface mucus
        
        more severe infections of the intestine result in villous atrophy and fusion
        
        reduce surface area for absorption of nutrients and resulting in malabsorption
      - CHRONIC ENTERITIS AND MALABSORPTION
        
        eg Johne's Disease (M. avian subspecies paratuberculosis)
        
        lamina propria of the intestine is infiltrated by massive numbers of macrophages containing causative mycobacteria (granulomatous enteritis)
        
        diffuse thinking of the intestinal mucosa by inflammatory cells results in the characteristic 'cobblestone' appearance
        
        eg. Inflammatory Bowel Disease
        
        commonly diagnosed in cats and ogs
        
        inappropriate immune response to dietary antigens or commensal bacteria
        
        laminate propria of the intestine is infiltrated by lymphocytes, plasma cells and/or eosinophils
        
        large numbers of plasma cells from an intestinal biopsy from a dog with inflammatory bowel disease
    - - HEPATITIS
        
        Acute often due to infection (viruses and bacteria)
        
        the liver is swollen and hyperaemic
        
        small pinpoint foci of necrosis may be seen through the capsule
        
        foal with equine herpesvirus-1 infection
        
        chronic
        
        ongoing inflammation and fibrosis disrupt the blood supply to the liver parenchyma
        
        results in further necrosis, inflammation and fibrosis that ultimately results in cirrhosis
        
        cirrhotic liver with nodules of attempted regeneration alternating with sunken bands of fibrosis
        
        land locked hepatocytes surrounded by bands of fibrosis (collagen stains blue)
      - the liver has a large capacity for regeneration as well as a considerable functional reserve so disease is often chronic before clinical signs develop
    - - PANCREATITIS
        
        acute
        
        aka acute pancreatic necrosis
        
        can be associated with obesity (eg. dogs) or abdominal trauma
        
        release of pancreatic enzymes into surrounding fat, causing fat necrosis
        
        animal can die acutely or recurrent bouts of pancreatitis lead to progressive pancreatic dysfunction (diabetes mellitus or exocrine pancreatic insufficiency
        
        chronic
        
        seen in the cat and occasionally the horse, causing progressive fibrosis
    - - NEPHRITIS
        
        since the kidney has a high functional reserve (70% of renal mass can be lost before renal failure develops) nephritis is often chronic at presenteation
        
        inflammation can arise in the glomeruli (glomerulonephritis), interstitial tissue (interstitial nephritis) or in the pelvis (pyelonephritis)
        
        interstitial nephritis
        
        white foci of inflammation throughout the cortex and medulla
        
        micrograph illustrates interstitial accommodation of lymphocytes and plasma cells
        
        ascending infections result in pyelonephritis
        
        nephrotic syndrome
        
        glomerulonephritis and/or amyloidosis may cause loss of substantial quantities of protein (esp albumin) into the urine
        
        heavy loss of protein into the urine (proteinuria) results in low plasma protein levels (hypoproteinaemia)
        
        results in low plasma oncotic pressure so that fluid is not drawn back into the blood from the tissues and so generalised oedema develops
        
        may also be loss of antithrombin III with resultant clotting problems
    - - CYSTITIS
        
        more common in females than males owing to the shorter urethra and consequenting increased risk of ascending urinary tract infection
        
        may be accompanied by considerable dilation of submucosal vessels = vascular ectasia
        
        bracken fern toxicity in cattle
        
        initially causes vascular ectasia, inflammation (cystitis) and haemorrhage (enzootic haematuria)
        
        can progress to transitional cell carcinoma of the bladder
    - - METRITIS
        
        can take place at two points
        
        at service where it is mild - an endometritis
        
        at parturition where it can be very severe and life threatening - particularly in assisted parturition, owing to metritis that involves whole wall of the uterus
        
        pyometra (pus in the uterus) occurs relatively commonly in bitches and is life threatening
    - - MASTITIS
        
        life threatening mastitis occurs shortly after parturition
        
        eg. gangrenous mastitis due to Staphylococcus aureus and coliform bacteria
        
        some organisms such as Staphylococcus aureus can cause gangrenous, acute and chronic forms of mastitis
        
        chronic mastitis results in progressive destruction of the glandular tissue and replacement by fibrous tissue eg. Streptococcus agalactiae
    - - PROSTATITIS
        
        inflammation of the prostate
        
        common in dogs
        
        ascending infection may result in abscessation
      - ORCHITIS
        
        inflammation of the testes
        
        uncommon
        
        Brucella abortus causes a granulomatous inflammation in bulls (B. canis rarely in dogs)
        
        chronic
        
        results in small fibroses testis and consequent subfertility
    - - LYMPHOPLASMACYTIC INFLAMMATION: PERIVASCULAR CUFFING
        
        several layers of cells around blood vessels in the perivascular space
        
        lymphocytes and plasma cells predominate
        
        common in viral infections or immune-mediated disease affecting the brain or spinal cord
      - encephalitis is inflammation of neural tissue of the brain
      - myelitis is inflammation of the spinal cord and often accompanies encephalitis ie. encephalomyelitis
      - meningitis is inflammation of the meninges
        
        purulent meningitis follows haematogenous spread of infection from umbilical infections and certain septicaemias
      - repair in the CNS involves proliferation of glial cells (especially astrocytes), which is termed gliosis
  - - - increased blood flow to the area
      - hyperaemia due to dilation of previously inconspicuous capillaries
    - - exudation of fluid from dilated blood vessels into the inflamed tissue
    - - increased blood flow
      - temperature of the inflamed portion approximates to internal body temperature
    - - due to chemical mediators released into damaged tissue
      - by local pressure on nerve endings from the exudate
    - - reluctance to use the inflamed portion
- - - - KARYORRHEXIS
        
        KARYOLYSIS
        
        CYTOPLASM
        
        sometimes stains brighter pink (more eosinophilic)
        
        nuclear staining with haematoxylin becomes faint and only the ghost outline of the nucleus remains
        
        rupture of cell membrane
        
        dissolution of nuclear structure
        
        nucleus has broken up into several dense pieces
      - normal nuclear structure is replaced by a very dense, heavily staining, small angular mass of chromatic
      - overall size has increased -> Na pumps failing -> water intake increases
        
        clumping of chromatin
        
        general swelling of cell
      - cytoplasm very dense pink, eosinophilic
        
        circled healthy renal tubule
  - - - Hypoxia - reduced oxygen supply
      - Ischaemia (ischaemic necrosis) - loss of blood supply
        
        consequences depend on
        
        type of cell - essential functioning cells (parenchyma) much more susceptible than the connective tissue supportive cells (storm)
        
        metabolic activity of the tissue - very active organs are more susceptible eg. heart
        
        whether or not there is a good or potential collateral blood supply eg. kidney (end arterial supply - lack of collateral therefore ischaemia more likely) vs lung (well supplied from multiple routes)
        
        occurs in three ways
        
        compression of the blood vessel from outside
        
        INTESTINAL TORSION
        
        common in horses
        
        lymphatic vessels get compressed first, simultaneous with venous outflow impediment
        
        organ swells due to congestion
        
        1 more item...
        
        INTESTINAL INTERSUSSCEPTION
        
        emergency
        
        gastroenteritis -> hypermobility -> intersussception
        
        narrowing of the vessel lumen due to mural (wall) thickening
        
        arteriosclerosis may occur in hypertension
        
        atherosclerosis is rare in animals (occasionally in dogs with hypothyroidism or diabetes
        
        blockage of the vessel lumen
        
        thrombosis and embolism
        
        hypertrophic cardiomyopathy (thickened left ventricular hear wall and mitral valve)
        
        increased size of muscle reduces amount of blood entering LV
        
        1 more item...
        
        erysipelothrix rhusiopathiae (bacterial infection causing dermal artery thrombosis
        
        aka diamond skin disease
        
        ingestion of Ergot (fungus) - causes severe vasoconstriction
        
        ear tips and digits become ischaemic
      - Infarction - sudden loss of blood supply to a portion of a tissue or organ (typically related to compromised vascular bed)
    - - black disease (infectious necrotic hepatitis) - haemorrhagic diseases caused by Clostridium novyi type B
        
        spores germinate in anaerobic environment creased by migration of liver fluke - Fasciola hepatica
        
        live in bile ducts but migrate through parenchyma -> anaerobic -> clostridium proliferate
        
        sharply demarcated line of coagulative necrosis
    - - PHYSICAL - burns, cold, frostbite, X-rays, pressure, pinching/crushing of tissue
        
        incorrect Burdizzo castration
        
        aims to crush the spermatic cord and testicular blood vessels but LEAVE THE VESSELS SUPPLYING THE SCROTUM INTACT
        
        incorrect crushing of scrotal vessels -> infection through inguinal canal
      - CHEMICAL - directly caustic or corrosive in action or exert their effects when absorbed and metabolised to a more toxic substance
        
        oak posoning (tannins): foal
        
        kidney - acute tubular necrosis
        
        tubules undergoing karyolysis
  - - - normal liver
      - zone of inflammation (line)
      - central zone of necrosis
    - - colour change
        
        in contrast to living tissue, dead tissue tends to be PALER partly because there is no circulation in dead tissue
      - consistency
        
        the appearance of the centre of the necrotic lesion will vary according to
        
        the type of agent responsible
        
        the tissue in which it is acting
    - - coagulative necrosis - remains firm
        
        GROSS
        
        firmer and drier on the cut surface
        
        still resembles in outline the adjacent viable tissue
        
        MICRO
        
        architecture of the tissue is preserved
        
        cells may appear somewhat larger and their outline may be lost
        
        cytoplasm appears structureless and homogenous
        
        important nuclear changes
        
        CAUSES
        
        bacteria producing toxins (especially clostridium spp.
        
        infarction
        
        some foci of viral replication eg. herpesvirus
        
        CANINE HERPESVIRUS-1 in a neonatal puppy
      - liquefactive necrosis - becomes liquid
        
        malacia (CNS)
        
        any necrosis in CNS
        
        no fibrous connective support tissue so just liquefies
        
        thiamine (Vit B1) deficiency
        
        causes cerebrocortical necrosis in ruminants
        
        an example of polio-encephalo malacia
        
        abscesses (anywhere in the body)
        
        pyrogenic (pus producing) organisms
        
        pus = dead and dying neutrophils, dead tissue and organisms
        
        bacteria cause necrosis and attract vast numbers of neutrophils which they also kill
        
        dying neutrophils release proteolytic enzymes which digest necrotic tissue
        
        kill further tissue cells
        
        kill other incoming neutrophils
      - caseous necrosis - looks like cottage cheese
        
        white to grey to yellowish in colour
        
        consistency varies according to fluid content
        
        dry and crumbly to cottage cheese
        
        mix of coagulation and liquefactive necrosis
        
        a large proportion of the necrotic tissue is composed of macrophages - recruited into the tissue to engulf the organism
        
        multinucleated giant cells (MNGCs) which increase macrophage
        
        caused by some specific organisms eg. mycobacteria - high lipid content cell wall which resists digestion and allows replication within the macrophage and evasion of phagolysis
        
        organisms burst the macrophage & are engulfed by other macrophages
        
        MICROSCOPY
        
        complete loss of architecture
        
        purplish necrotic material due to - random intermixing of the nuclear and cytoplasmic components that stain with haematoxylin and eosin
      - fat necrosis - hard soap-like appearance of affected body fat (saponification)
        
        GROSS
        
        areas of focal opacity
        
        very hard consistency
        
        PATHOGENESIS
        
        adipocytes die
        
        fat broken down into fatty acids
        
        combine with Ca2+, Na2+, K+ ions to forms soaps (saponification)
        
        soaps are foreign to the body
        
        1 more item...
        
        ENZYMATIC NECROSIS
        
        release of pancreatic enzymes esp. lipase from a damaged pancreas into the adjacent mesenteric fat eg. pancreatitis
        
        TRAUMATIC NECROSIS
        
        in the subcutaneous tissue following trauma to the area
        
        quite common in the brisket of recumbent animals due to the prolonged pressure on the area
        
        DIET RELATED
        
        rarely, in cats associated with diets lacking antioxidants eg. vitamins E
      - gangrene - mostly a post-necrotic change
        
        post necrotic change eg. putrefaction of dead tissue
        
        WET GANGRENE
        
        primary - agent which initially kills the tissue, further putrefies it
        
        secondary - dead tissue being invaded by organisms which putrefy it
        
        DRY GANGRENE - a type of mummification
        
        occurs on the extremities eg. post spticaemic salmonellosis in calves
        
        air passing over the extremity removes the fluid content of the dead tissue
        
        appears leathery
      - sequelae to necrosis
        
        surface necrosis can be shed (sloughs)
        
        after vesicle (blister) formation
        
        basement membrane intact - epithelium regenerates = erosion
        
        basement membrane breached, there is a host inflammatory response - tissue repairs by fibrosis = ulceration
        
        internal necrosis repaired or contained by fibrous tissue
        
        small foci replaced by fibrous tissue = scarring eg. Ascaris suum in pig liver (milk spot)
        
        larger foci are encapsulated by fibrous tissue: sequestrum
        
        often with areas of bone necrosis
- - - - irreversible cellular injury results in cell death
      - degenerative changes are a continuum and the point at which injury transitions from reversible to irreversible is not always clear-cut
    - - dose of injurious agent acting upon the cell
        
        virus
        
        toxin
        
        bacteria
      - duration for which it acts
      - vascular flow - for nutrient supply
        
        well supplied organs are both likely to be targeted by septicaemia but are also able to mount a more effective immune response
      - type of cell injured: highly active cells such as hepatocytes, proximal convoluted tubular epithelium of the kidney and cardiac myocytes are most prone to inury
        
        kidney, liver and heart tend to be 3 main target organs for cellular injury
    - - plasma membrane damage (outer and organelle)
      - calcium entry into the cell
      - mitochondrial swelling and vacuolation
      - lysosomal swelling
        
        leads to rupture and further cell lysis via lysosomal enzymes
    - - decrease in ATP
        
        loss of energy-dependent cellular functions
      - membrane damage
        
        mitochondrion
        
        cell death
        
        lysosome
        
        enzymatic digestion of cellular components
        
        plasma membrane
        
        loss of cellular contents
      - increase in intracellular calcium
        
        protein breakdown/DNA damage
      - reactive oxygen species
  - - - acute cellular swelling
      - the cells may swell up like a balloon prior to their destruction
        
        or there is a discrete bleb (vacuole) of fluid within the cytoplasm
      - causes include mild hypoxia, viral infection and toxins
        
        feature of certain viral infectionseg. FMDV
        
        rupture of adjacent cells leads to formation of vesicles (blisters)
        
        SQUAMOUS EPITHELIUM OF PIG MOUTH
        (vesicles & inclusion bodies)
      - INJURY
        
        hypoxia
        
        ATP production decreases
        
        Sodium pump efficiency decreases
        
        sodium and water move into cell/potassium moves out of cell
        
        osmotic pressure increases
        
        1 more item...
      - accumulation of watery material
      - PATHOLOGICAL FEATURES
        
        mildest, earliest detectable degenerative change: impairment of cell membrane integrity
        
        first stage in injury to the cell - likely to be momentary phenomena passing more quickly to more serious damage
        
        GROSS: somewhat paler than normal, on sectioning, may slightly bulge
        
        MICROSCOPIC: moderate swelling of the individual cells
        
        EVENTUALLY excess fluid transferred to the endoplasmic reticulum (ER)
        
        swells and eventually fragments, leaving a fluid vacuole in the cytoplasm
        
        commonly occurs in very metabolically active cells with well-developed pumping mechanisms, therefore have worse effects
        
        hepatocyte
        
        renal tubular epithelial cell
        
        pancreatic acing cell
    - - an important intracellular abnormality that can be easily recognised post-mortem
      - accumulation or increase of fatty substances within the cytoplasm of specific cells such as the parenchyma of the liver, kidney and heart
        
        very common in liver disease - blockage of pathways metabolising fatty acids into phospholipids, cholesterol esters, acetates, ketone bodies and triglycerides lead to ACCUMULATION OF FATTY ACIDS IN CELLS RATHER THAN DEPOSITS IN BODY FAT STORES
      - DOES NOT REFER TO BODY FAT STORES
      - GROSS APPEARANCE
        
        LIVER
        
        may be greatly increased in size
        
        tan to yellowish in colour
        
        very prone to rupture with slight pressure (friable)
        
        clinically often presents with IA haemorrhage as has ruptured due to pathology
        
        on cutting through surface the underlying parenchyma bulges outwards
        
        parenchyma is dull, yellowish and greasy (fat adheres to scalpel/PM knife)
        
        KIDNEY
        
        cortex is pale compared to medulla
        
        cats normally store fat in renal tubular epithelium so is normal to see some lipid here - must be relatively more
        
        HEART
        
        flabby with streaks in the papillary muscles
      - MICROSCOPIC APPEARANCE
        
        LIVER AND KIDNEY
        
        globules or vacuoles of varying size in the cytoplasm of the cells
        
        nucleus pushed to periphery but remaining normal
        
        fat forms single large fat filled vacuole per cell
        
        HEART
        
        tiny groups of vacuoles dispersed along the myofibrils
      - IDENTIFICATION
        
        Oil-Red-O
        
        Sudan black
        
        fat dissolves in alcohols used in processing of sections to make slides leaving empty vacuoles - to prove fat is present must stain frozen sections
      - CAUSES
        
        STARVATION
        
        increased mobilisation of fat in response to body energy needs
        
        the liver is unable to cope with them all properly and so they are stored here as neutral fats
        
        more common
        
        OVEREATING
        
        obesity where the dietary intake is greater than the energy expenditure
        
        fat is temporarily stored prior to movement to the body fat sotres
        
        LIPOTROPE DERANGEMENT
        
        lipotropes are substances which hasten the removal of fat from the liver cells
        
        some are the amino acids that facilitate conjugation of the fat with proteins to form the lipoprotein that is excreted from the cell
        
        deficiency of these eg. choline and methionine in the diet, lea to fatty change within the cells
        
        METABOLIC DISEASE
        
        diseases associated with deranged carbohydrate metabolism - glucose not available for uptake into the tissues
        
        alternative energy sources are used ie. fat is mobilised from reserves like starvation
        
        Diabetes mellitus
        
        lack of insulin (type 1 diabetes) or lack of reactivity to insulin (type 2 diabetes) results in cells that are unable to use glucose as an energy source switching to alternative energy sources such as fat
        
        Ketosis
        
        in ruminants, excess demand on glucose reserves
        
        in sheep caused by twin lambs (called pregnancy toxaemia)
        
        in high yielding dairy cows shortly after parturition
        
        shortage of energy
        
        HYPOXIA
        
        an inadequate supply of oxygen to the tissues - any condition that reduces the oxygen supply to the tissues will cause fatty change in the liver
        
        hepatocytes begin to degenerate and thus struggle to process normally
        
        Anaemia
        
        reduced circulating red cell numbers
        
        caused by sustained loss of erythrocytes from the vessels
        
        chronic haemorrhage
        
        excessive destruction of erythrocytes within the vessels (haemolysis)
        
        Ischaemia
        
        reduced blood supply to a tissue
        
        chronic venous congestion (slowing of blood flow through the vasculature)
        
        due to a failing heart
        
        TOXINS
        
        often a preamble to NECROSIS
        
        bacterial and fungal toxins
        
        either produced in the bloodstream from circulating bacteria (septicaemia/bacteraemia)
        
        produced elsewhere and absorbed into the bloodstream
        
        chemical toxins
        
        CCI4
        
        phosphorus
        
        arsenic
        
        lead
        
        some plant poisonings
        
        will cause fatty change in the very early stages of poisoning
      - DISTRIBUTION
        
        fatty changes affecting the liver may be diffuse (all hepatocytes affected (eg. metabolic disease) or zonal (eg. circulatory disease)
        
        diffuse - starvation
        
        zonal - chronic passive congestion, cow
        
        focal - tension lipidosis
        
        liver is attached to body wall: close to attachment there is minor stress on hepatocytes but is NOT CLINICALLY RELEVANT
        
        zonal (one specific lobule) fatty change in congestive heart failure leads to a nutmeg liver with fatty change in periportal areas (well supplied) and congestion in periacinar areas (central veins)
    - - degeneration of connective tissue involving deposition of mutinous (myxoid) material in the extracellular matrix - replacing collegen
      - CLINICAL EXAMPLE
        
        valvular endocardiosis
        
        degeneration affects heart valves and results in progressive cardiac failure
        
        very common in CKCS
        
        usually left atrioventricular valve
        
        heart valve must be watertight to prevent backflow
        
        in affected dogs becomes LEAKY - increases heart workload & pushes into cardiac failures
        
        jet lesions - area of fibrosis occurring in inner endocardium of left atrium
      - MICROSCOPICALLY
        
        nodules visible - should be smooth
        
        pink = collagen
        
        purple = mucin
      - MUCOUS METAPLASIA OF EPITHELIAL SURFACES
        
        physiological adaptive change rather than pathological degeneration
        
        involves goblet cells of wet mucous membranes and mucous glands increasing in number
        
        results in accumulation of mucus
        
        increased mucus production results in:
        
        increased lubrication
        
        soothes inflamed surfaces
        
        traps and dilutes harmful agents
        
        carries antibodies against infectious agents
        
        enables removal of particulates
        
        typically beneficial - if very very excessive can become pathological
    - - descriptive term meaning glassy
      - applied to several types of degeneration or infiltration involving protein
      - MICROSCOPIC
        
        structureless and stains pinkish red with eosin in H&E
        
        hyaline degeneration of skeletal muscle fibres refers to the homogenous and pale appearance of the cell cytoplasm eg. WMD pre necrosis
        
        visible distortion of usual muscle fibres
        
        hyaline casts ar the casts of protein found in the urine of animals with renal failure and proteinuria
        
        coagulates in nephron
      - hyaline membranes are the layers of protein adhering to the surface of damaged alveoli in animals with severe respiratory distress
        
        severe extensive alveolar necrosis
        
        exudation of protein as part of inflammatory response - is then deposited on alveolar membrane and prevents effective gas exchange
        
        often acutely progressive
    - - CAUSES
        
        chronic inflammatory process elsewhere in the body - most cases
        
        tumours as in plasma cell and thyroid tumours
        
        prion disease eg. Bovine Spongiform Encephalopathy
      - CHARACTERISED
        
        by accumulation of protein that misfiles forming beta pleated sheets and becomes highly resistant to proteolysis
        
        the protein that accumulates differs in different types of amyloid eg. serum amyloid A in chronic inflammation and immunoglobulin light chains in plasma cell tumours
      - much less common than lipidosis but is the end point of a number of disease processes
      - PATHOGENESIS
        
        STIMULUS
        
        unknown (carcinogen)
        
        monoclonal B lymphocyte proliferation
        
        plasma cells
        
        immunoglobulin light chains (soluble precursor: misfolded protein)
        
        1 more item...
        
        chronic inflammation
        
        macrophage activation
        
        interleukin 1 and 6
        
        liver cells
        
        1 more item...
        
        mutation
        
        abnormal protein (soluble precursor: misfolded protein)
        
        ABNORMAL PROTEIN
      - PRIMARY AMYLOIDOSIS (AL)
        
        AL - amyloid light chain
        
        made up of complete immunoglobulin light chains secreted by plasma cell tumours (multiple myeloma)
        
        affected animals have monoclonal gammopathy (continuous high level of gamma globulin) with abnormal protein in urine (Bence-Jones proteinuria)
      - SECONDARY AMYLOIDOSIS (AA)
        
        AA - amyloid associated protein
        
        also called Reactive Systemic Amyloidosis
        
        secondary to inflammatory reactions, particularly chronic infections
        
        deposited in teh renal glomeruli in dogs and cattle
        
        Renal Amyloidosis
        
        GROSS
        
        pale cortex
        
        glomeruli appear as white dots
        
        waxy texture
        
        will stain yellowish brown with an iodine solution
        
        subsequent treatment with dilute sulphuric acid turns them blue-purple
        
        precursor is serum amyloid A
      - MICROSCOPIC CHANGES
        
        deposition of a pink homogenous material in the glomerulus progressively replacing the epithelium and endothelium
        
        the amount of amyloid varies between individual glomeruli
        
        cuffs of the same material around tubules
        
        stains pink with Congo red, and the amyloid fibrils appear an apple green colour in polarised light
        
        look for accumulation distorting renal glomeruli
      - EFFECTS OF RENAL AMYLOIDOSIS
        
        sustained loss of protein (mainly albumin) into urine
        
        reduces osmotic potential of blood to attract fluid back into the blood at the venous end of the capillary bed
        
        results in oedema of the subcutis and abdominal cavity
        
        nephrotic syndrome
        
        heavy proteinuria + subcut oedema + accumulation of fluid in BC
      - HEPATIC AMYLOIDOSIS
        
        amyloid deposition in liver causes hepatomegaly with a high risk of haemorrhage (becomes swollen and friable)
      - ENDOCRINE ASSOCIATED AMYLOIDSIS
        
        amyloid deposition can occur in endocrine organs eg. the islets of langerhans in the pancreas
        
        particularly - many be a prediabetic change but no current association
        
        functional problem - resistance to proteolysis causing buildup
    - - principal veterinary association is high level corticosteroid exposure (therapeutic or secondary to hyperadrenocorticalism)
      - glycogen is normally present in substantial amounts in the liver and muscle where it is a readily utilisable sources of energy
      - GROSS
        
        moderate amounts of glycogen do not produce appreciable alteration in the gross appearance of the organ
      - MICROSCOPIC
        
        foamy cytoplasmic vacuoles, similar to fat
        
        accumulation of glycogen (hence staining for fat - reversible change)
    - - VIRAL INCLUSION BODIES
        
        accumulations of viral nucleic acid or protein
        
        nuclear, cytoplasmic or both
        
        subcellular localisation indicates type of virus
      - ABNORMAL STORAGE PRODUCTS
        
        hereditary storage diseases in which there is a missing or defective cellular enzyme
        
        build up of intermediate metabolites in cytoplasm
        
        usually affects all tissues
        
        CNS is particularly vulnerable because it cannot regenerate
        
        manifestation is typical here
    - - fibrin like red smudging
      - focal death of vessel wall cells
      - consists partly of degenerated muscle and elastic fibres and partly of an increased amount of protein, including fibrin, around degenerated fibres
      - suggests either
        
        LOCAL HYPERSENSITIVITY REACTION
        
        type 3 hypersensitivity
        
        arthus reaction
        
        affecting BV wall by depositing damaging immune complexes
        
        DAMAGE SECONDARY TO HYPERTENSION
        
        high blood pressure
        
        adaptive response is proliferation of wall - eventually narrows lumen, becomes poorly perfused
        
        undergoes fibrinoid change
        
        eventually necroses
- - - - involves pigments from external environment
      - accumulation of excess amounts of foreign pigments in the tissues
      - enter via skin, lung, intestinal tract
      - carbon (anthracosis)
        
        most common exogenous pigment
        
        usually inhaled, esp urban environments
        
        carbon -> lung parenchyma, macrophages -> ultimately tracheobronchial lymph nodes
        
        inert, thus remains for life
        
        pulmonary anthracosis
        
        typically within alveolar macrophages
        
        histologically, carbon in lungs intra- or extra cellular (alveolar walls, around bronchioles, bronchi
      - dusts (pneumoconiosis)
        
        pneumoconiosis = inhalation & retention of dusts eg. silicosis and asbestosis
        
        small particles, evade mucociliary system of nose/upper respiratory tract
        
        chronic irritation associated with pulmonary fibrosis and/or tumours (mesotheliomas)
      - carotenoids (lipochrome)
        
        fat-soluble yellow/orange
        
        plant origin, including beta-carotenes (Vit-A)
        
        stain
        
        many normal tissues
        
        adrenal cortex
        
        testes
        
        corpus luteum
        
        serum
        
        animal products
        
        egg yolks
        
        butter
        
        body fat
        
        horses
        
        channel island cattle
        
        differentiate from icterus!!!
      - iatrogenic
        
        tattoos - pigment (incl C) loose in dermis or in macrophages
        
        tetracycline-based antibiotics - exposure during development of teeth and bone (yellow/brown)
        
        iron dextran injections (young piglets) - can stain muscle and thus devalue meat
    - - formed inside the body
      - accumulation of excess amounts of normal pigments
      - melanin
        
        skin/hair/iris
        
        protective
        
        melanocytes contain granules (melanosomes) which synthesise melanin
        
        quantities affected by
        
        genetics (albinism)
        
        UV light exposure
        
        chronic damage (NB: includes depigmentation)
        
        Cu deficiency (tyrosinase)
        
        cofactor of tyrosine which is required for melanin production
        
        melanosis
        
        congenital accumulation in some tissues, in some species
        
        lung (ruminants, pigs)
        
        meninges (sheep)
        
        organs affected may be condemned at meat inspection
        
        hyperpigmentation
        
        due to increase of melanocytes or increased melanin production
        
        chronic skin disease/endocrine disease (hyperadrenocorticism - Cushing disease)
        
        very common in
        
        hypopigmentation
        
        congenital/hereditary or acquired (Cu deficiency)
        
        chronic inflammation of skin (could over/under produce melanin)
        
        leads to leakage of melanin into dermis (melanin incontinence)
        
        especially common in autoimmune disease eg. lupus depigmentation
        
        melanoma
        
        tumour of melanocytes
        
        grey horses (perineal)
        
        dogs
        
        cat (skin, mouth, digit, eye)
        
        melanocytoma (benign) much more common in animals than humans vs. malignant melanoma
        
        may be melanotic
      - blood/bile pigments
        
        haemoglobin (Hb)
        
        colour normally varies with oxygenation
        
        in haemolytic diseases
        
        plasma becomes red
        
        kidneys dark red & urine red (haemoglobinuria)
        
        haemosiderin
        
        intracellular protein-iron complex, derived from splitting Hb (iron storage)
        
        Golden brown/yellow
        
        local accumulation eg. old bruises
        
        diffuse/excessive accumulations with increased red blood cell breakdown (haemolysis)
        
        perl's Prussian blue reaction
        
        bilirubin
        
        yellow or yellow-brown
        
        remains of haeme (after iron removed & stored)
        
        found in macrophages at sites of erythrocyte breakdown
        
        if accumulated throughout body causes diffuse yellowing of tissues = icterus
        
        occurs with
        
        excessive production
        
        inaequate removal of bilirubin
        
        CLASSIFICATION OF ICTERUS (determine ratio of conjugation to determine classification)
        
        pre-hepatic (haemolytic) icterus
        
        excessive production of bilirubin due to haemolysis
        
        increase in unconjugated bilirubin in blood
        
        unconjugated bilirubin overwhelms albumin and liver conjugation -> bilirubin backup
        
        hepatic icterus
        
        hepatocyte damage (decreased conjugation)
        
        liver cannot conjugate properly
        
        increase in unconjugated bilirubin in blood (or both unconjugated and conjugated bilirubin)
        
        post hepatic (obstructive) icterus
        
        obstruction of bile excretion
        
        increase in conjugated bilirubin in blood
        
        EXAMPLES OF ICTERUS
        
        pre-hepatic
        
        large haemorrhage into tissues
        
        infectious
        
        leptospirosis
        
        babesiosis
        
        immune mediated erythrocyte breakdown (AIHA)
        
        hepatic
        
        liver damage by chemical or toxic causes
        
        heaptocellular tumour
        
        post hepatic
        
        obstruction of bile outflow
        
        gallstone
        
        tumour
        
        inflammation
        
        haematin
  - - - DYSTROPHIC
        
        = local deposition in degenerate or necrotic tissues
        
        granulomas (TB)
        
        dead parasites
        
        Vit E/Se deficiency
        
        normal serum Ca (but may be accentuated by hypercalcaemia), Ca metabolism normal -> just accumulates locally
        
        formation
        
        dead/dying cells no longer able to regulate Ca2+ influx, start to accumulate
        
        History: irregular blue-purple fragments
        
        usually irreversible. may cause organ dysfunction if very marked
        
        indicates previous tissue damage
        
        necrotic inflamed myocardium
        
        intervertebral disc degeneration & mineralisation (can then prolapse)
        should not be able to see the discs - less elastic
      - METASTATIC
        
        = deposition of Ca2+ salts in otherwise normal tissue
        
        always result from high blood Ca2+ secondary to disturbed Ca metabolism
        
        increased secretion PTH
        
        secondary to chronic renal failure or dietary
        
        renal secondary hyperparathyroidism
        
        chronic renal failure causes retention of PO4- & loss of Ca2+
        
        2 more items...
        
        hypercalcaemia due to hyperparathyroidism
        
        PRIMARY
        
        rare (Parathyroid tumours)
        
        SECONDARY
        
        more common
        
        2 more items...
        
        APPARENTinappropriate secretion of parathyroid hormone related protein (PHrP) by malignant non-parathyroid tumours
        
        circulation Ca2+ deposits in various tissues
        
        bone destruction eg. tumours of bone (multiple myeloma)
        
        Vit D disorders eg. Vit D intoxication (eg. calcinogenic plants); cholecalciferol-containing rodenticides
        
        morphology ~ dystrophic calcification
      - = deposition of Ca2+ salts (& smaller amounts of Fe, Mg, others) in tissues other than bone and teeth
      - common, variety of conditions
      - affected tissue white, gritty, granular
    - - Oxalate
        
        ethylene glycol (antifreeze) poisoning, small animals
        
        sheep/cattle - ingestion of oxalate-contains plants
        
        absorption from GIT. metabolism (liver) to toxic products
        
        filtered by glomeruli -> acute tubular necrosis
        
        crystals can be seen in histological sections
        
        ruminants, also neuromuscular dysfunction due to calcium chelation
        
        concentrated alcohol drip will saturate the ethanol dehydrogenase that metabolises to toxic products and allows excretion
- - - - the earlier on in the gestation period the more severe the defect
      - if very early on, may result in foetal re-absorption or abortion
      - important to take detailed clinical history, perform gross PME and take tissue samples to look at histology and to test for infectious agents/toxins exposure/deficiencies if suspected
    - - amorphous globosus
        
        generally occur as a twin with a live counterpart
      - atresia ani
        
        failure of anus development/imperforate anus
      - hydrocephalus
        
        calf f24h old: failed to suckle then faded and died
        
        bulbous head
        
        sunken eyes
        
        dilated ventricles -> obstruction of CSF outflow -> atrophy due to high pressure
      - ventricular septal defect
        
        2 month old lamb, poor BC
        
        in respiratory distress then died
        
        enlarged heart
        
        pale, very rounded liver
        
        congested due to right sided cardiac failure -> blood congestion -> hypoxia
        
        left ventricle should be significantly thicker
      - diaphragmatic hernia
        
        5mo old kitten: sudden onset lethargy and collapse
        
        could be traumatic or congenital - lack of trauma signs around indicate congenital
      - neurological clinical signs, delayed onset...
        
        lysosomal storage disease: enzyme deficiency
      - infertility discovered at puberty
        
        white heifer disease
        
        freemartinism (testosterone exposure in utero)
      - Brachycephalic Obstructive Airway Syndrome
        
        changes
        
        stenotic nares
        
        extended soft palate
        
        everted laryngeal saccules
        
        hypoplastic trachea (v v thin)
      - Dam infected with Schmallenberg virus during pregnancy
    - - VIRAL DISEASE
        
        Border disease virus
        
        Hairy-shaker disease
        
        similar to BVDV in cattle
        
        virus targets cerebellum -> causes cerebellar hypoplasia
        
        caused by infection of dam by Border disease virus (a pestivirus)
        
        BVDV
        
        schmallenberg virus
        
        lamb pathology
        
        spinal curvature (kyphosis)
        
        shortening of lower jaw (brachygnathia inferior)
        
        very flexed legs - can't straighter (arthrogryphosis)
        
        big and furry legs
        
        pathogenesis
        
        arhtrogryposis
        
        torticollis
        
        brachygnathia inferior
        
        unilateral loss of cerebral and thalamic parenchyma with eccentric dilation of the lateral and third ventricles
        
        skeletal muscle has few normal muscle fibres - most have myofibrillar hypoplasia (cannot unflex legs, very thin muscles)
        
        cervical spinal cord histology has mycromyelia with severe reduction of grey matter and few neurons in one ventral horn
        
        infection during days 60-18- of gestation
        
        differentials (cf BVDV, BTV, AKAV/AV)
        
        vertebral column curvature (kyphosis, lordosis, scoliosis, torticollis (twist))
        
        arthrogryposis
        
        joint contraction of the limbs
      - TOXINS
        
        ingestion of corn lily (Veratrum californium)
        
        ingestion by dam between days 12-14 of gestation
        
        contains alkaloids that interfere with neural tube development
        
        may produce cyclopia in lambs
        
        Griseofulvin (ringworm treatment)
        
        if given to pregnant queen in first trimester can cause a cleft palate
      - DRUGS
      - IONISING RADIATION
      - NUTRITIONAL DEFICIENCY
        
        copper deficiency
        
        primary deficiency is low nutrition
        
        secondary deficiency is uptake issue
        
        degeneration of the white matter in the brain and spinal cord due to hypomyelination/demyelination
        
        swayback
        
        lambs born dead or ataxic at birth
        
        destruction of subcortical white matter
        
        enzootic ataxia
        
        low level in milk
        
        ataxia develops at 6mo onwards
        
        demyelination of dorsolateral and ventromedial tracts in the white matter of the spinal cord
      - PHYSICAL TRAUMA
      - ANOXIA
      - CHROMOSOMAL DEFECTS
  - - - decrease in the size of cells and organ
      - occurs after the organ has reached normal size eg. canine pancreas
      - GROSS
        
        the atrophic organ or tissue appears smaller and perhaps paler
      - MICRO
        
        cells of smaller size
        
        cells of inactive appearance
        
        might get a relative increase in the supportive connective tissue
      - can be PHYSIOLOGICAL or PATHOLOGICAL
        
        lactating mammary gland - atrophy is a normal physiological process during normal dry up of milk
        
        PATHOLOGICAL
        
        deficient nutritive supply
        
        starvation/decreased blood supply
        
        skin
        
        liver
        
        diffuse, systemic
        
        pressure
        
        compression by a nearby lesion such as a tumour
        
        may also compromise blood supply
        
        decreased work load
        
        immobilisation of a fractured limb results in atrophy of the muscles and bones
        
        loss of endocrine stimulation
        
        prolonged steroid therapy results in atrophy of zone fasiculata in the adrenal gland
        
        denervation
        
        eg. atrophy of temporal muscle with damage to trigeminal nerge
        
        neurogenic atrophy
        
        more localised
        
        serous atrophy of fat
        
        indicates starvation
        
        progressive mobilisation of fat
        
        fat deposits are severely depleted and clear gelatinous material remains
        
        occurs following severe debilitation and weight loss
        
        adipocytes are smaller
        
        more ECM
    - - transformation of one differentiated cell type into another differentiated cell type
      - cause
        
        injury
        
        hormonal stimulation
      - tissue types
        
        connective tissue changes to cartilage and bone
        
        epithelial tissue changes from cuboidal or columnar to squamous
      - eg.
        
        osseous metaplasia in hind limb muscle of a horse following injury to connective tissue and long term chronic irritation
        
        prostate epithelium undergoes metaplasia from glandular to stratified squamous epithelium
        
        testis with Sertoli cell tumour producing oestrogen
        
        lung transformation from callous to squamous epithelium when overly irritated by smoke
    - - increase in the size of an organ due to an increase in size of the individual cells (increase in number of cell organelles)
      - occurs in tissues that can undergo little cellular replication
      - PHYSIOLOGICAL/FUNCTIONAL or PATHOLOGICAL
        
        pathological
        
        compensatory hypertrophy
        
        occurs when one of a paired organs is damaged or lost eg. the kidneys
        
        obstruction hypertrophy
        
        hollow organs may become thickened around an obstruction
        
        intestine
        
        bladder
        
        gall bladder
        
        try to increase peristalsis = thickening
        
        hormone mediated hypertrophy
        
        hyperthyroidism in older cats
        
        thyroid hormones increase protein synthesis and have a trophic affect on organs
        
        there are limits to hypertrophy
      - eg. hypertrophic cardiomyopathy
        
        genetic
        
        malfunction of cytoskeletal protein
        
        compensation with cardiomyocyte size
    - - an increase in the size of an organ due to an increase in the number of cells present within it
        
        controlled proliferation
      - cells are well differentiatied and tissue structure is normal
      - hyperplastic response stops when the inciting agent which triggers it ceases
      - hyperplasticity tissue is more prone to injury by chemicals and also may be more prone to undergo neoplastic change in some cases
      - eg.
        
        nodular hyperplasia in liver
        
        raising of capsule
        
        different colour
        
        no tissue change like fibrosis etc.
        
        cortical hyperplasia of adrenal gland
        
        probably age related
      - PATHOLOGICAL
        
        hormonal stimulation
        
        parathyroid hyperplasia in chronic renal failure
        
        prostatic hyperplasia in older male entire dogs
        
        response to irritation, cell loss or injury
        
        in these cases, the hyperplasia is considered a reiterative response
        
        may occur together with hypertrophy
    - - a precancerous change in epithelium
        
        carcinoma in situ
        
        following papillomavirus infection
        
        mitotic figures
        
        loss of contact inhibitiion
        
        no invasion as PRE cancerous
      - abnormal growth within a tissue during development
        
        renal dysplasia
        
        cannot support metabolic needs
        
        small glomeruili
        
        incorrectly lined tubule
    - - type of injurious agent
      - extent of injury
      - duration of injury
      - cell type affected
        
        cells which divide and replicate continuously
        
        skin
        
        GI tract
        
        cells which are capable of cell division in response to demand
        
        liver
        
        lung
        
        cells which are not capable of division
        
        CNS
        
        cardiac muscle