Intro and Acute Inflammation Flashcards
What is Inflammation?
Local physiological response to tissue injury
What is acute inflammation?
Initial and transient series of tissue reactions
The benefit of inflammation
Prevents spread of infection by destroying microorganisms and wailing off abscess cavities
What is Evisceration?
examination of all organs in situ by a y-shaped incision
Describe the steps of Acute Inflammation (TVVN)
Tissue injury reaction
Vessel dilation
Vascular protein leakage
Neutrophil polymorph recruitment
What are the outcomes of Acute Inflammation (RSOC)?
Resolution
Suppuration
Organisation
Chronic Inflammation
What is Suppuration?
Pus (neutrophils and bacteria in all states) formation
Caused by pyogenic bacteria (S.aureus, S.pyrogenies, Neisseria and coliform)
Healing of the pus forms a pyogenic membrane and leads to granulation tissue and scarring
How is a scar formed in Organisation?
- Tissue loses ability to regenerate specialised cells
- Dead tissue and exudate removed by macrophages
- Fibroblasts proliferate via TGF-beta = fibrosis
- Tissue replaced with granulation tissue
- Collagen is produced by granulation to form a scar
What are the causes of Acute Inflammation (MHPCT)?
Microbial Infection Hypersensitivity Reaction Physical Agent Chemicals Tissue Necrosis
How do viruses kill cells?
Intracellular Multiplication
How does bacteria kill cells?
Release inflammation initiating exotoxins
Release endotoxins
In what instances are hypersensitivity reactions important?
Parasitic Infection
Tuberculous Inflammation
How does a hypersensitivity reaction damage tissue?
An altered state of an immunological response causes a wrong reaction
How do physical agents damage tissue?
Physical trauma
Radiation
Burning
Cooling
How do chemicals cause inflammation?
Gross tissue damage
Direct irritation to Inflammation
How does tissue necrosis cause inflammation?
Hypoxic tissue dies
Peptide released from dead tissue
What are the physical characteristics of acute inflammation (RHSPF)?
Redness Heat Swelling Pain Function Loss
Why is there redness in Acute inflammation?
Caused by dilation of small blood vessels
Why is there heat in Acute inflammation?
Increased blood flow (hyperaemia)
Vascular dilation
Systemic Fever from chemicals
Why is there swelling in Acute inflammation?
Oedema - fluid in extravascular space
Movement of inflammatory cells
Formation of Connective Tissue
Why is there pain in Acute inflammation?
Distortion from oedema
Pressure from Pus
Bradykinin, Prostaglandins and Serotonin
Why is there loss of function in Acute inflammation?
Movement is consciously/reflex inhibited
What accumulates in the early stages of acute inflammation in Extracellular space?
Oedema Fluid
Fibrin
NEUTROPHIL POLYMORPHS
Describe the acute inflammatory process?
Vessel gets wider and increases blood flow
Increases vascular permeability
Formation of fluid exudate
Cellular exudate formation
How is Cellular exudate formed?
Neutrophil polymorph movement to extravascular space
How is capillary calibre controlled?
They have no smooth muscle but are single cell thick
How is arteriolar blood flow controlled?
They have smooth muscle and form precapillary sphincters to regulate flow through capillary bed
What happens to precapillary sphincters during acute inflammation?
The sphincters relax
Blood flow increases
Redness and Heat
What happens to osmotic pressure in normal capillaries?
There is a high osmotic pressure in the vessel due to plasma proteins
Fluid returns to the vascular compartment
What happens to hydrostatic pressure in normal capillaries?
There is a high hydrostatic pressure at the arteriolar end
Fluid is forced into extravascular space
Fluid returns at the venous end at low hydrostatic pressure
What happens to pressure in acutely inflamed capillaries?
High hydrostatic pressure
Plasma proteins leak into extravascular space
High osmotic pressure
More fluid leaves the vessel than returns
Vascular Permeability Increases
What is fluid exudate?
The protein-rich fluid that leaves
What are the causes of immediate transient vascular permeability?
Chemical mediators (histamine, bradykinin, NO2, C5a, Leukotrine B4 and platelet activating factor)
What are the causes of immediate sustained vascular permeability?
Severe direct vascular injury
What are the causes of delayed prolonged vascular permeability?
Endothelial cell injury (x-ray, bacterial toxins….)
What is the diagnostic histological characteristic of acute inflammation?
Neutrophil polymorph accumulation in extracellular space
What are the stages of neutrophil polymorph emigration?
Margination
Adhesion
Emigration
Diapedesis
What is neutrophil margination?
Cells travel in the plasmatic (peripheral) zone of blood vessels due to loss of IV fluid
Increase in plasma viscosity so slow flow at the site of inflammation
What is neutrophil adhesion?
Pavementing occurs in venules
Increased leucocyte adhesion with endothelium
What is pavementing?
Adhesion of neutrophils with endothelium at the site of acute inflammation
What is neutrophil emigration?
NEUTROPHILS/ Eosinophil polymorphs/ macrophages insert pseudopodia between ENDO. CELLS
Move between the cells through to the BASAL LAMINA and then the VESSEL WALL
What is pseudopodia?
Cytoplasm filled temporary PROJECTION directed in the way of movement
How do leukocytes travel?
They migrate through venule walls and veins
They don’t normally exit capillaries
What is diapedesis?
The passive movement of RBC escape from vessels via hydrostatic pressure
What does the presence of a large number of red blood cell suggest in the extracellular space?
Implies severe vascular injury
Why does acute inflammation spread?
Injured tissue releases chemical substances which spread to uninjured tissue
What causes the up-regulation of adhesion molecules initially?
Histamine and Thrombosis production
What is the result of the initial increased Histamine and Thrombosis production?
Very firm neutrophil adhesion
What are the endogenous chemical mediators of acute inflammation?
Histamine and Thrombosis
What do the endogenous chemical mediators cause (VNCII)?
Vasodilation Neutrophil Emigration Chemotaxis Increased vascular permeability Itching and pain
What is chemotaxis?
The attraction of neutrophil polymorphs toward certain chemicals
What does histamine do?
It causes vascular dilation
Transient phase of Increased vascular permeability
Why does Histamine have an immediate effect?
It is stored in preformed granules which release histamine quickly
Where is Histamine found?
Mostly in MAST CELLS
Basophils
Eosinophils
Platelets
What stimulates Histamine release?
C3a and C5a complement
Lysosomal proteins released from neutrophils
What is mast cell degranulation?
The release of Histamine granules from mast cells
What are the 6 types of chemical mediators?
Histamine Thrombosis Lysosomal compounds Eicsanoids (prostoglandin) Seretonin Chemokine
What are the 4 plasma enzymatic cascade systems (CKCF)?
Complement
Kinins
Coagulation Factors
Fibronylitic system
What is Rubor?
Redness
What is Calor?
Heat
What is Tumor?
Swelling
What is Dolor?
Pain
What is the purpose of the plasma enzymatic cascade systems?
To produce inflammatory mediators
How can the cascade system remove/destroy antigens?
Lysis
Opsonisation
What is Opsonisation?
Phagocytosis enhancement by Plasma Opsonins (factors)
What activates the cascade system during acute inflammation?
Tissue Necrosis - complement activating enzyme released
Infection - complement activating antigen-antibody complexes formed (Classical Pathway) complement activating endotoxins released by gram-negative bacteria (Alternative Pathway)
What is the Classical pathway?
Infection - complement activating antigen-antibody complexes formed
What is the Alternative Pathway?
Infection - complement activating endotoxins released by gram-negative bacteria
How does the Hageman factor (Coagulation factor XII) activate the Kinin complement?
Factor XII and Plasmin convert Prekallikien to Kallikrein
Kininogens are then converted to Kinins
What can cause the conversion of Prekallikrien?
Activated factor XII and Plasmin
Leucocyte Proteases
What 2 systems does Hageman factor (Coagulation factor XII) activate to produce fibrin?
Fibrinolytic System
Coagulation System
How is Fibrin produced by the Fibrinolytic pathway?
Hageman factor activates the Fibrinolytic system
Plasmin degrades into Fibrin
How is Fibrin produced by the Coagulation pathway?
Hageman factor activates the coagulation system
Fibrin is produced
What are the chemical mediators of Vascular Dilation?
Histamine
Prostoglandins
NO2
PAF
What are the chemical mediators of increased vascular permeability?
Transient- Histamine
Prolonged - Bradykinin, NO2, C5a, leucotriene B4, PAF
What are the chemical mediators Leucocyte adhesion?
Adhesion Upregulation - IL-8, C5a, Leucotriene B4, Il-1 and TNF-Alpha
What are the chemical mediators of Neutrophil Polymorph Chemotaxis?
IL-8 and Leucotriene B4
What is the Cytokine IL-4?
Interleukin 4
What is the Cytokine TNF- alpha?
Tumour necrosis factor- a
What do tissue macrophages do in acute inflammation?
They secrete chemical mediators in response to injury/infection
Which chemical mediators have an effect after Histamine and Thrombin?
IL-1
TNF-alpha
What does IL-1 and TNF do to endothelial/epithelial cells and fibroblasts?
Secrete MCP-1 which attracts neutrophil polymorphs (Chemotaxis)
How do blood monocytes become macrophages?
Blood monocytes enter inflammation site
Become macrophages when leaving blood vessel
Becmome more metabolically active, motile and phagocytic
How is Phagocytosis enhanced?
Opsonisation by antibodies / complement
In acute Inflammation, are macrophages or neutrophil polymorphs most dominant?
Neutrophil Polymorphs
Macrophages do not dominate until NP number decrease and M number increase by proliferation
What is the role of macrophages in acute inflammation?
Clear away tissue/damaged cells
What aids digestion of Inflammatory Exudate?
Lysosomal enzyme discharge from macrophages and neutrophils
What is the lymphatic ?system
Collection of vessels, tissues and organs
What does the lymphatic system carry?
It carries excess fluid and particulate from tissues to the bloodstream AKA lymph
what are afferent lymphatic vessels?
These vessels enter into the lymph nodes, flowing into the sinus space below the capsule of the node.
What is lymph?
A colourless, watery bodily fluid carried by the lymphatic system, consisting mainly of white blood cells
What are germinal centres?
Places within secondary lymph nodes to which B cells migrate to proliferate and differentiate based on an antigen response
Describe the transport of of lymph in vessels
Interstitial Space has Lymph
which filters into
Capillaries feed into
Collecting vessels into Afferent vessels into trunks/nodes
What valves are present in the lymph vessels?
Mini-valves - in capillary endothelium letting lymph in
Semilunar valves - promote forward travel (with muscular contraction) in collecting vessels and prevent backflow
As well as fluid, what else can enter the lymph nodes
Pathogens
Proteins
Tumour cells
How is lymph filtered of pathogens at the nodes?
The nodes contain lymphocytes such as B and T cells to produce immune response (B cells can produce antigen specific response)
How does the lymphatic system help target acute inflammation?
The Lymphatic channels dilate
They drain away oedema fluid of inflammatory exudate
This decreases the amount of tissue oedema fluid
How are neutrophil polymorphs charecterised?
Most abundant lymphocyte
Under H+E stain, blue nucleus and pink cytoplasm
List the roles of neutrophil polymorph in acute inflammation
Microorganism Adhesion
Phagocytosis
Intracellular death
Lysosomal release
Describe microorganism adhesion
Microorganisms are opsonised by immunoglobulins/complement components
Alternative Pathway- bacterial lipopolysaccharide activate complement to make C3b(Opsoniser)
Classical Pathway - antibody-bacterial antigen complex activates complement to make C3b(Opsoniser)
How can neutrophils bind to micro-organisms?
Imunnoglobulins bind to the FAB region of micro-organisms
Fc component is exposed
Neutrophils bind to the Fc region then ingest
Describe neutrophil phagocytosis
Opsonisation of the particle
Phagocyte ingests by surrounding particle with pseudopodia
Arms of pseudopodia fuse and form phagosome around particle
Lysosomes bind with phagosome to initiate intracellular killing
Describe intracellular killing
Neutrophil polymorphs contain noxious agents….
- H202 reacts with myeloperoxidase in the presence of a halide = potent agent
- lysozyme and lactoferrin
What happens when lysosomal products are released?
Local tissue is damaged by proteolysis from elastase and collagenase
Coagulation factor XII activated
Leukocytes attracted
-Some compounds increase Vas. Permeability
-Some compounds are pyrogens
What are pyrogens?
They are compounds that induce systemic fever by acting on the hypothalamus
What is the role of mast cells in Acute inflammation?
mast cell degradation - releases histamine and metabolises arachidonic acid into leukotrienes, prostaglandins and thromboxane
Types of Inflammation (descriptive)
Serous - fluid release Supparative - pus filled Membranous Pseudomembranous Necrotising - gangrenous
Beneficial effects of Fluid Exudate
Toxin dilution - carried away in lymphatics
Antibody entry (via inc. vas. permeability) - neutralise toxins, lysis via complement system or phagocytosis via opsonisation
Drug transport
Fibrin formation - from fibrinogen which can trap microorganisms and allow the formation of granulation tissue
O2 and nutrient delivery - Increased fluid flow delivery for highly metabollic neutrophils
Immune response - Lymphatic system
Harmful effects of lysosomal enzymes
Tissue Digestion - by collagenases and proteases
Swelling - harmful in children such as acute epiglottis swelling from influenza (airway obstruction) - acute meningitis = increased cranial pressure = ischaemic damage
Inappropriate Inflammatory Response - Type 1 Hypersensitivity reactions (environmental allergies)
Describe resolution
Complete restoration
- minimal cell death
- occurrence in regenerative systems
- Rapid response to cause
- Good vascular drainage
What is an abscess?
A collection of pus where the bacteria is inaccessible to antibiotic drugs and antibodies
What happens if an abscess burst?
The abscess cavity collapses and is taken over by organisation and scarring
What is the result of an abscess in a hollow organ?
Mucosal layers of the outflow tract can fuse by fibrin causing an empyema(pus filled pocket)
What is organisation?
Tissue replacement by granulation tissue because….
-Large amounts of fibrin formed
-Necrotic tissue
Exudate/debris cannot be removed
How can acute inflammation progress to chronic
- If stimulus is not removed
- The nature of the exudate changes
- Neutrophil polymorphs replaced by lymphocytes, macrophages, giant cells and fibroblasts
What are the systemic effects of Inflammation
- Pyrexia (fever)
- Reticuloendothelial reactive hyperplasia
- Haematological changes
- Amyloidosis
What causes pyrexia
Neutrophil polymorphs/Macrophages produce endogenous pyrogens (IL-2) which set thermoregulation at a higher temperature
-Pyrogen release is stimulated by phagocytosis, endotoxins and immune complexes
What are the constitutional symptoms of inflammation
Malaise (weakness)
Anorexia
Nausea
Weight loss- negative nitrogen balance due to increased energy use with inflammatory mediators
What is reactive hyperplasia of the reticuloendothelial system
Lymph node enlargement
Splenomegaly (Increased spleen size)
What are the haematological changes of inflammation
Increased levels of….
- white blood cells
- neutrophils (pyogenic infection and tissue destruction)
- eosinophils (allergic disorders and parasitic infection)
- lymphocytes (Chronic/ viral infections and whooping cough)
- monocytes (Bacterial infections)
Why may anaemia be a result of inflammation
Blood loss into the inflammatory exudate (ulcerative colitis) or due to haemolysis by bacterial toxins
What is Amyloidosis
Long standing chronic inflammation caused by elevating serum amyloid A protein which can deposit into various tissues
