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Pathology Pt.2 - Coggle Diagram

- - - - Regeneration: results in the complete restitution of lost or damaged tissue
        
        A completete resititution of growth (in tact tissue framework) or compensatory growth (ie kidney/liver)
        
        Cells w/ a high proliferative capacity
      - Repair: restore (something damaged, faulty, or worn) to a good condition
        
        Cells with a reduced proliferative capacity
        
        occurs in most mamalian cells
        
        Damaged tissue frame work
        
        Resulting in scar formation
      - Fibrosis: abnormal excessive/extensive formation of fibrous tissue
        
        Persistent chronic inflammation
        
        increased collagen synthesis and deposition
  - - - Proliferation (increase)
      - Apoptosis (decrease)
    - - Determines the no. of cells in the baseline pop
      - Innate replicative capacity
        
        Labile Cells
        
        Epithelium, cells in skin, gut and bone marrow
        
        Continuously renewing
        
        Stable cellls
        
        Limited capacity for renewing
        
        fribroblasts, endothelium, smooth mucsle
        
        Pernament Cells
        
        Neurons, cardiac or skeletal muscle
        
        No renewable capacity
    - - Pluripotent or Multipotent cells can create new cells to add to the base population
  - - - Promote cell growth, locomotion, contractility, angiogenesis
      - Ex. Epidermal Growth, Transforming Growth Factor
      - Types
        
        Paracrine (adjacent) vs Endocrine (target sites)
    - - Non-Cellular component of the connective tissue
      - Function
        
        Scaffolding for tissue renewal
        
        Maintence of cell growth and differentiation
        
        Storage of Growth factors
      - Macromolecules
        
        Adhesive glycoproteins
        
        Proteoglycans and hyularon
        
        Fibrous structural proteins
  - - - • Stable cells – will no repair if there are no growth factors
    - - • Permanent cells – have little capacity to regenerate, therefore stem cell have to be present for any replication to take place
    - - • Labile cells – will no regenerate if the ECM is damaged
    - - Liable, Stable or pernament
  - - - > 24hrs
      - Inflammatory cells (PMN and Mo)
      - Release of cyokines and GFs that iniate fibroblasts and endothelaila cells and stem cell migration
    - - leaky blood vessel proliferation into site to allow for infiltrate and nutriets, waste and debris to be removed
    - - >3-7 days
      - Granulation tissue forms + leaky vessels, inflam cells, fibroblasts and mature endothelial cells (RED and SPONGY!!)
    - - >14 days
      - Luekocyte infiltatre, odema, hypervasc dissapear
      - Increased collage deposition
    - - ECM deposition, cllagen is turned over and scar can contract
    - - Primary Intention
        
        ie sugical incision, minimal disruption to ECM, small scar
      - Secondary Intention
        
        ie tooth socket, more intense inflammtion, collagen formation and scarring and wound contraction
    - - Extrinsic pathway is activated (TF) is released and converst VII to VIIa which goes to the common pathway to activate X to Xa to then convert Prothrombin (II) to thrombin (II) and finally fibrinogen (I) to fibrin (Ia)
      - Platelet adhesion, activation and aggregation occurs to form the priamry plug
  - - - Age
      - Metabolic Status
        
        ie Diabetes
      - Assoc. Diseases
        
        ie Cushing Disease
      - Medications
        
        Excessive glucorticoids
    - - infection, FB and debirs in wound
    - - Wound dihiscence/rupture
        
        inadequate graulation tissue
      - hypertophic/keilodscarring
        
        excessive collagen (possible thermal injury)
      - Excessive contraction (seen after burns)
      - Proud Flesh = exuberent grnaulation tissue
    - - Alveolar osteitis
        
        Early loss of the clot (fibrinolysis)
      - Persistent granulation tissue
        
        local factors (FB, irritants) preventing scar tissue formation
      - Exophytic Clot
        
        Poor quality lcot that extrudes out of the socket and rebleeds
- - - - Serum antibodies that are produced by plasma cells and bind to antigens in order to assist with their elimination
      - Targeted and Specific
      - Memory
        
        Memory T cells = Recuited after exposure
        
        Produce antibodies
        
        Memory = immunity
        
        enhanced response to future challenges from known antigens
      - Tolerance
        
        Recognition from self vs non-self
    - - B Lymphocytes
        
        Plasma cells
        
        Antibody
        
        IgA
        
        Neutralises micobes in respiratory/Gi tracts (mucosal peentration)
        
        IgG
        
        opsonize microbes and target them for phagocytosis
        
        Activates classical complement pathway = leading to phagocytosis
        
        Plays a role in passive immunity (crosses the placenta)
        
        IgE
        
        combats parasties along side mast cells/eosinophils
        
        IgM
        
        Activates classical complement pathway = leading to phagocytosis
        
        Antibodies circulate and multiply (clonal expansion)
        
        ○ Agglutination
        
        ○ Neutralisation
        
        ○ Opsonisation
        
        ○ Immobilisation of bacterial cilia
        
        ○ Mediate NK cell attack
        
        ○ Mucosal protection (IgA)
        
        Cell receptors for antigen recognition
        
        Memory B Cells (coated w/ antigen receptors)
        
        Derived and matured from the Bone marrow
      - T helper cells
        
        CD4 cells help B cells make antibody and the IgM/IgG switch
        
        Memory T cells
  - - - The action of cytotoxic cells that activate other immune cells and help eliminate pathogens and infected host cells
      - FIRST DEFENCE: Physical Barries (skin), Cillia, Commensal Flora, Gastric contents, fever(temp)
      - General and Non-specific
      - Cellular components
        
        Leukocytes (myeloid)
        
        Mo = phagocytosis and APC
        
        Dendritic Cells
        
        APC
        
        PMN
        
        Phagocytosis
        
        Mast Cells
        
        Releases histamine and other inflammatory agents
        
        Eosinophils
        
        killing-antibody coasted parasites
        
        Complement
        
        a) Opsonization & Phagocytosis
        
        C3b binds the mircrobe and activates Mo to phagoctose
        
        b) MAC
        
        C3b binds the mircrobe and activates MAC which lysis the cell
        
        c) Inflammatory stimulation
        
        C3b cuases C3a/C5a to be released and recuits luekocyres (PMN) to destro the mircrobe
        
        Activation
        
        Alternative Pathway
        
        Microbe-mediated via binding of C3b
        
        Classical Pathway
        
        Antibodies bind the microbe and allow for c3b binding
        
        Lectin Pathway
        
        Mannose binds lectin = causing the activation/binding of teh C3b protien
        
        Toll-Like Receptors
        
        Recognition and respond to different microbes
        
        Found in a number of tissues to activate the innate immune system
        
        Lymphoid cells
        
        T Lymphocytes
        
        T helper Cells (CD4)
        
        Release cytokines to activate Mo, inflammation and aifd in differentiation of B and T lymphoctes
        
        Cytotoxic T cells (CD8)
        
        Recognise infected cells and kill them
        
        NK cells (lymphoid)
        
        Cell lysis
        
        Express inhibitory receptors that recognize MHC molecules that are normally expressed on healthy cells, and are thus prevented from killing normal cells
  - - - Lymph nodes
        
        Cortex
        
        Medulla
        
        Afferent/Efferent vessels
      - Thoracic Duct
        
        Where the lymph joins the venous system
      - Thymus
        
        Where T cells are derived from
      - Spleen
- - - - RBC
    - - Plateletes
    - - WBCs
    - - Lymphocytes
  - - - biconcave disc
      - live span ~120days
      - x4 polypeptide chains and x4 iron rings = bind upto 4 O2 atms bind the 4 haemrings
    - - Iron overload
        
        may be genetic can cause organ damage
    - - Elevated haemoglobin
        
        primary (prolif RBCs), secondary (hypoxia or COPD) = elevated RBC conc.
    - - Definition
        
        Low Hb = Reduced oxygen carrying capacity of the blood
      - Dx
        
        Reduced Haemotocrit (total RBC/total blood vol)
      - Classification
        
        Morphology/Colour
        
        Microcytic
        
        Iron deficiency
        
        Causes: dietary, absoption failure, blood loss or increased deman
        
        Thalasemmia (haemolytic)
        
        reduced production of globin chains (alpha and beta)
        
        causes reduced O2 carrying capacity (microcytic and hypochromic) and haemolytic
        
        Readily removed to the spleen spleen due to reduced Hb
        
        Nomocytic
        
        Anemia of chronic disease
        
        Hepcidin, IL-1, TNF decrease release of iron, reduced RBC lifespan, and reduced response erythropoietin
        
        Macrocytic
        
        Metabolic defects = B12 and folate deficiencies
        
        Thymidine deficiencies cause RBC apoptosis due to poor RBC formation
        
        Also fewer divisons along teh lineage = larger RBCs (macrocytic)
        
        Haemolytic
        
        Altered RBC structure
        
        Sickel Cell Anaemia
        
        Mutated hb - creates sickle shaped cells
        
        causes : infection, acidosis, dehydration
        
        Chronic haemolysis of defected sickle cells
        
        Sequale = Sickel crises: microvasc occlusions and tissue damage
        
        G6PD Deficiencies
        
        Gluathione deficiencies resulting in periodic haemolysis due to oxidative stress
        
        Causes: drugs (apsirin, penicillin), foods (broad beans)
        
        Denatured RBC = Heinz Bodies = damage RBC body and are haemolysis
        
        We may see "Bite Cells" when phagocytes attempt to remove it
        
        Sphereocytosis
        
        No biconcave disc = spherical = destroyedb
      - Features
        
        Oral Manifestations
        
        Mucosal pallor
        
        Candida Infections (angular chellitis)
        
        Atrophic glossitis
  - - - Leukopenia
      - reactive leukocytosis
      - reactive lymphadenitis
    - - lymphoid neoplasms
      - myeloid neoplasms
      - histiocytic neoplasms
      - Leukemia
        
        Dental Considerations
        
        Management
        
        Prognosis of Leukemia dependant
        
        Stage and severity dependant
        
        Oral manifestations = disease or tx induced
        
        Anemia
        
        mucosal pallor, angular chelitis, glossitis
        
        Neutropenia
        
        opportunistic infection, ulcers
        
        Thrombocytopenia
        
        petechia, thrombosis, procedural bleeding
        
        Classification
        
        Type
        
        Acute
        
        Proliferation of immature functionless cells
        
        Dominant feature: bone marrow failure
        
        Rapid Onset/progression
        
        Better response to tx
        
        Chronic
        
        Proliferation of differentiated/functioning cells
        
        Poorer response to tx
        
        Slow onsewt/progression
      - Lymphoma
        
        malignant lymphocytes that accumulate in the lymph nodes
        
        Types
        
        Hodgkins Lymphoma
        
        B lymphoid lineage
        
        presence of REED-STERNBERG CELLS
        
        Large-abnormal lymphocytes!!
        
        Cervical nodal disease, malignant lymphocytes in LN
        
        Better prognosis compared to NHL
        
        Non-Hodgkins Lymphoma
        
        Absence of REED-STERNBERG CELLS
        
        Classifications
        
        Indolent
        
        survival measured in years
        
        Aggressive
        
        survival measured in months
        
        Highly aggressive
        
        survival measured in weeks
        
        Features
        
        Lymphadenopathy
        
        Solid mass in lymph nodes
        
        Dental Considerations
        
        Oral manifestations
        
        lymphadenopathy, tumor mass at extra-nodal sites, swelling on hard palate
        
        Management
        
        Based on stage and severity of disease and prognosis
        
        Current, past and possible and future regimes
  - - - Reduced No.
        
        Thrombocytopenia
        
        Decreased bone marrow production
        
        ie Leukemia
        
        Increased splenic sequestration
        
        ie portal HTN
        
        Accelerated destruction (drug, immune or infection mediated)
        
        Management
        
        Blood tests for platelet no. = bleeding/bruising
      - Reduced function
        
        nb: function
        
        Adhere to vWF
        
        Activate and degranulate (release Factor V & VIII + fibrinogen)
        
        Aggregate = form crosslinks creating a platelet plug
        
        Disorders of adhesion
        
        Von Willebrand's Disease
        
        Carries VIII, disease will cause a reduction in this factor
        
        Disorder of platelet adhesion
        
        Management: TXA, Desmopressin (stimulates endothelium vWF release), vWF infusion, Factor VIII infusion
        
        Disorders of activation
        
        Chediak Higashi Syndrome
        
        Drugs (aspirin/NSAIDs)
        
        Disorder of Aggregation
        
        Drugs (clopridogrel)
        
        Afibrinogenaemia
    - - Inherited
        
        Haemophilia A or B
        
        A = x-linked recessive disorder for VIII
        
        Management: TXA, Desmopressin (stimulates endothelium vWF/VIII release), vWF infusion, Factor VIII infusion
        
        Dental Considerations
        
        Haemotology Involvement + Avoid emergency dental care
        
        Concurrent HIV, Hep B or C??
        
        nb: VIII maybe be antigenic and cause a immological response
        
        Emergencies
        
        Bleeding into Tissue spaces
        
        Possible airway compromise if bleedings occur in the retromandibular area, sublingual ect
        
        Factor V Leiden
        
        Hypercoagulable state = risk to VTE
        
        pts are ofetn anticoagulated
      - Aquired
        
        Disseminated intravascular coagulation (DIC)
        
        Formation of fibrogenic clots = causes widespread haemorrhage
        
        Liver Disease
        
        reduced clotting factors produced
        
        Vitamin K deficiency
        
        Drugs
        
        Warfarin/Heparin
        
        This may be due to surgery/DVT prophylaxis w/ long stays on hospitals
- - - - via endothelin = vasocontriction
      - Endothelium is damaged and releases endothelin and tissue factor
    - - Adhesion
        
        via vWF
      - Activation
        
        Shape change and cross-linking
      - Aggregation
        
        Haemostatic (priamry) plug
    - - Extrinisc Pathway
        
        Tissue Injury = VII ---> VIIa + release of Tissue factor (thromboplatin)
        
        Together TF-VIIa = Factor X -->Xa
      - Intrinsic Pathway
        
        Contact activation (damaged surface) = XII --> XI --> IX --> Xa
      - Common Pathway
        
        Factor Xa = prothrombin (Factor II) --> thrombin (Factor IIa)
        
        (prothrombinase complex)
        
        IIa = fibringogen (I) --> fibrin (Ia) + XIII --> XIIIa
        
        Leading to (fibrin) clot formation
        
        Thrombin
        
        Promotes:
        
        Endothelium activation: NO, PGI2
        
        Smooth M. activation
        
        Converts fibrinogen to fibrin for stabiliseing the primary plug
        
        Nutrophil adhesion and monocyte activation
        
        Factors V and VIII postive feedback on the cascade
    - - Maintained by
        
        NO = inhibits platelet aggregation
        
        PGI2 (prostacyclin) = inhibits platelet aggregation
        
        Thrombomodulin = binds thrombin, activates Protein C which in turn inactivates factors V and VIII
        
        Heparin Sulphate = antithrombin activity via inactivation of factir IX and X
      - Failures in fluid homeostasis
        
        local trauma, hypercoaguability, secondary to other diseases
    - - Fibrin = Plasminogen --> Plasmin
      - Plasmin
        
        Degrades fribrin, fibringogen anf Factor V and VIII
  - - - Endothelial Injury
      - Abnormal Blood flow
        
        Ie Arrythmia or Fibrilation
      - Hypercoaguability
        
        Familal
        
        Factor v mutations
        
        Prothrombin mutation
        
        Elevated factotrs VII, IX or fibrinogen
        
        Aquired
        
        MI, AF
        
        Prolonged immbolization
        
        prothetic heart valves
        
        Hepari-induced thrombocytopenia
    - - Arterial grow retrogrde direction from point of attachement
      - Venous thrmobi grow in the direction of blood flow
    - - Local vascular occlusion
      - Distal embolization
  - - - Familial
        
        Immune mediates, idiopathic or functional
      - Aquired
        
        Drugs
        
        Aspirin works by irreversibly inhibiting the enzyme cyclo-oxygenase (COX-1) which is required to make the precursors of thromboxane within platelets. This reduces thromboxane synthesis. Thromboxane is required to facilitate platelet aggregation and to stimulate further platelet activation.
        
        Antibiotics and Alcohol
  - - - A& B = Factor VIII definecies
      - Males (X-linked)
    - - Type 1 reduced circulating vWF
      - Type 2 functional definecies of vWF
    - - Reduced Vitamin K
    - - Warfarin (vitamin k dependant)
        
        Vitamin K-dependent coagulation factors are factors II, VII, IX, X, proteins C
    - - APTT
        
        Intrinsic Pathway
        
        Evalutates if anticoagulants are effective
      - PT
        
        Extrinsic Pathway
        
        Ability to clot
      - INR
        
        Normalised test that compaires PT (patient) against normal reference range and an international standard
    - - Platelet pr Factor Tranfusions
      - Desmopressin (stimulates vWF)
      - Antifibrinolytics = TXA (inhibits plasminogen to plasmin)
      - Clotting Profiles = Determining risk of bleeding
- - - - Lack of response to own antigens
      - live in harmony with own cells
    - - Deletion of self-reactive T and B cell in central lymphoid organs are killed by apoptosis
    - - Suppression by regulatory T cells
      - Anergy = functionally inactive
      - Clonal deletion (apoptosis)
  - - - IgE mediated
        
        Occurs w/n 30mins of exposure
      - Antigen exposure induces an IgE Ab response (First exposure)
        
        Antigen is taken up by dentdritic cells (APC) and merges w/ MHC molecules which presents them to Th-Cells
        
        Activated Th-Cells release cytokines that stimulate B-cells to produce palsma cells which secrete IgE
        
        IgE ab bine mast cells and a person is now sensitized to the antigen
      - Secondary expoures antigens activate IgE abs on mast cells causing it to degranulate
        
        Histamines, leukotrienes, prostaglandins, and/or cytokines are released
        
        These chemicals are the cause of hives, hay fever, asthma and anaphylactic shock
        
        Localized anaphyalxis
        
        an allergic skin condition characterized by the formation of a wheal and flare pattern
        
        Generalised anphyalxis
        
        Antigen enters the bloodstream and becomes widespread and the reaction affects almost the entire body (systemic)
        
        Loss of fluid from the blood vessesl can cause hypovaolemic shock and swelling of airways
        
        Asthma (atopic)
        
        inhaled allergen causes chemical mediators from IgE to stimulate increased mucous secretions and spasms of the bronchi
      - Management
        
        Adrenaline (Epipens)
        
        Immunotherapy
        
        = desensitization techniques used to decrease the hypersensitive reaction through specific IgG ab
    - - Cytoxic Hypersensitivity
        
        Occurs within hours after of exposure
      - Transfusion Reactions
        
        Reaction within the ABO blood groups
        
        A Type blood have A antigen , and anti-B antibodies, ect
        
        ABO incompatibility cuases fever low BP, pain and nausea
      - Hemolytic Disease of the Newborn
        
        Results when mother is Rh- and baby is Rh+
    - - Immune Complex-Mediated Hypersensitivity
        
        Occurs within hours-days
      - antigen-antibody complexes activate complement and stimulate neutrophil and basophil degranulation
      - antigen-antibody complexes will deposit on the walls of small blood vessels in skin, joints and kidneys = tissue damage
        
        Dessiminated intravascular coagulation
        
        When immune complexes preciptate in blood
        
        ex. SLE or Serum sickness
    - - Delayed Cell-Mediated Hypersensitivity
        
        Occurs with days after exposure
      - T-Cell mediated reaction rather than antibodies
        
        Contact Hypersensitivity
        
        T-cells that release cytokines when they come into contact with the same antigen
        
        Tuberculin skin test – a positive test results when circulating antibodies for TB
        
        sensitized T-cell reactions release of cytokines/macrophages at injection site
  - - - Dx: Detection of a reaction, primary not secondary reaction to an infection, absence of another cause for the disease
      - May result from genetic suseptibility = causing self-reactive lymphocytes
      - Exogenous factors include: Drugs, UV irrataion, virus infcetions and estrogens
    - - SjÖgren syndrome
        
        Affects the salivary and lacrimal glands
        
        Symptoms
        
        causes dryness of eyes and mouth
        
        Xerostomia
        
        Dental caries, mucosal atrophy, candidosis, taste dysfuntion
        
        CD4+ T cells attack self-antigens in gland
        
        Autoantibodies are present
        
        Anti-SS-A, anti-SS-B may also present
        
        Types
        
        Secondary = 2nd to other auto immune disease
        
        Primary = limited to salivary/lacrimal glands
        
        Management
        
        Supportive abd symptom based
        
        Oral Tx
        
        hydration, good OH
        
        Cholinergic agents (pilocarpine)
        
        Regular dental checks
        
        Eye Tx
        
        lubricating agents
        
        Surgical methods
        
        Systemic Tx
        
        Steroid Therapy
        
        Immunosuppressants
      - Hashimoto's
      - Grave's disease
      - Systemic sclerosis (scleroderma)
        
        CD4+ T cells release cytokines causing inflammation/tissue damage leading to fibrosis
        
        Can be localised or systemic
        
        demis becomes sclerotic and fibrotic
        
        fingers may become stiff and claw like
        
        Difficulty swallowing and getting dentures in
        
        nb: Variant - CREST SYNDROME
        
        Calcinosis, Raynaud's Phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
        
        Raynaurd's Pheno - reduced blood flow to fingers
    - - Systemic Lupus Erythematosus (SLE)
        
        Autoantibodies react to selfantigens to form immune complexes (Type III)
        
        Typical Symptoms
        
        Butterfly rash (skin)
        
        Kidney = renal failure
        
        Joint = polyarthritis
        
        80% 10 year survial rate
      - Rheumatoid arthritis
        
        Multisystem
        
        T-cells to release cytokines (especially TNF) causing inflammation and tissue damage, and formation of plasma cells and antibodies against joint
        
        Rh Factor (80%) & IgM-IgG immune complexes, which deposit in joints
        
        Hands, knees, elbows, shoulders, TMJ
        
        Fingers: ulner deviation or swan neck deformities
        
        Chronic synovitis with pannus formation
        
        Treatment: steroids, anti-TNF agents
    - - Primary
        
        Genetic (primary)
        
        X-Linked (Brunton)
        
        Common variable Immune Definency (CVID)
      - Secondary
        
        Infections (Aquired)
        
        AIDS (HIV)
        
        Retrovirus HIV (1,2) = Profound immunodeficiency T3 cells (CD4, CD8)
        
        Immunosuppression (Aquired)
        
        Post-op Infection (Aquired)
        
        Other
        
        Amylodosis
        
        Aquired buildup of protenacious fibrils and cause chronic inflammation and disorders