MOD2 Flashcards
5 causes for acute inflammation
- physical agents
- chemicals
- microbial infections
- hypersensitivity reactions
- anything causing tissue necrosis
3 Key features + some characteristics
- Vascular and cellular Rxns: accumulation of fluid exudate and neutrophils
- Controlled by a variety of chemical mediators
- Meant to be protective but it can lead to complications and systemic effects
-short-acting, innate, stereotyped
Clinical features - 5 cardinal signs
Rubor, tumor, calor, functio laeso, dolor
Steps of the vascular phase
- transient vasoconstriction
- vasodilation (tumor and calor) increasing blood flow
- increased permeability due to a balance of hydrostatic (forcing things out due to relative pressure) and oncotic pressures (Net flow of protein-rich fluid going into the spaces - leads to an edema)
What is starling’s law
Movement of fluid across a vessel wall governed by the balance between hydrostatic and osmotic pressure between intra and extravascular space
Name the mechanisms of vascular leakage
- endothelial cell contraction - causing a gap mediated by histamine, C5a and NO
- endothelial cell injury: direct (trauma, chemicals, toxins) and indirect (ROS, proteolytic enzymes)
- structural reorganization: being transported from one side to the other. Mediated by interleukin 1 and TNF
- Transcytosis: VEGF induces angiogenesis, increasing the channels in endothelial cells
How does vascular stasis occur and what does it help?
Losing fluid leads to increased concentration of RBCs, resulting in decreased velocity and stasis
Aids neutrophil margination
What is transudate and where/why would you see it
Lower protein content:
In heart failure, you would have a back up of blood in the venule end - increasing hydrostatic pressure and causing more plasma to leak out - edema
Name the types of exudate and what is exudate
High protein content
- purulent (full of pus) would see in meningitis and TB
- Hemorrhagic
- serous (blister-like, fluid strips overlying epithelium, pain and profuse exudate, few inflamm. cells make it clear unless there’s a bacterial infection
- fibrinous: fibrin leaking out gives a bread and butter appearance. e.g; surface of the heart
Primary leukocyte in acute inflammation? How many hours is it active for
Neutrophils, 6-24 hours
What aids rolling of neutrophils
Selectins are expressed by endothelial cells and bind to carbohydrate ligands called Slex on neutrophils
Aided by IG-1 and TNF
What aids adhesion?
Integrins - expressed by neutrophils bind to integrin ligand on the endothelium, aided by C5a, leukotriene B4, IL-1 TNF
What aids diapedesis and what is it?
Neutrophils emigrating through the endothelium
Chemotaxins (e.g; C5a, leukotriene B4, endogenous cytokines, exogenous bacterial products, clotted blood)
Stimulate neutrophils to migrate through the inter-endothelial cell junction
Receptor ligand binding through selectins and integrins
What is chemotaxis
movement along concentration gradients of chemoattractions and chemotaxins
3 steps in how Neutrophils escape from the vessels (not diapedesis)
- relaxation of inter endothelial cell junction
- digestion of BM
- movement
What is opsonization? Name 3 common opsonins and 4 receptors they can bind to
Marking an antibody for ingestion of phagocytes (e.g; neutrophils and macrophages)
C3b, plasma proteins, IgG
Toll-like receptors, G-protein coupled receptors, opsonin receptors, cytokine receptors
Explain the two killing mechanisms of the phagolysosome
- Oxygen-dependent: free radicals released into the phagosome, superoxide converted to hydrogen peroxide through myeloperoxidase from neutrophil granules
- Oxygen Independent: uses enzymes; lysozyme, protease, nuclease and phospholipase to perforate holes in the microbial membrane
Where do endogenous chemical mediators come from
plasma proteins, leukocytes and local tissues
Where do exogenous chemical mediators come from
gram (-) bacteria
Name the 2 vasoactive amines and what produces them
Histamine - increases permeability and vasodilation, platelets, basophils and MAST cells
Serotonin: immediate-early response to injurious stimuli - causes dilation, permeability and pain. Platelets
Name a vasoactive peptide, what it does and where it comes from
Bradykinin; from the plasma precursors kininogen (in the kinin system)
Pain permeability and dilation
Where do prostaglandins come from and what do they do?
Name 2 ‘Other’ chemical mediators
From arachidonic acid metabolites from membrane phospholipids, vasodilation, fever pain and itching
NO, leukotrienes
What does the coagulation/fibrinolytic cascade form and activate?
Form thrombin and fibrin, and activates the kinin and complement systems
What is a byproduct of the kinin system
Gram (-) bacteria
What composes and activates the complement system? What does it do?
Normally inactive enzymatic proteins C3b and C5a made in the liver and present in the blood are activated by: antibody-antigen complexes in infection, proteolytic enzymes from necrotic cells, gram (-) bacteria, by-products of kinin and fibrinolytic systems
Generates: C3b - opsonin, C5a attracts neutrophils and C5-9 Membrane attack complex that causes lysis through cell membrane perforation
List 5 examples of anti-inflammatories
Aspirin/NSAIDs antihistamine corticosteroids TNF alpha antagonists - infliximab leukotriene antagonists
What 3 things are TND alpha antagonists used for
Crohns, rheumatoid, psoriatic athritis
2 Hallmarks of acute inflammation
- exudate
2. infiltrate of inflammatory cells
What are 3 benefits of exudation?
- delivers plasma proteins, immunoglobulins, inflammatory mediators to the area of injury
- Diluting toxins and reducing their impact
- Edema elicits lymphatic drainage: delivering antigens to the immune system and microorganisms to phagocytes
What is a consequence of edema eliciting lymphatic drainage?
Lymphadenopathy can occur if there’s too much fluid draining into the lymph system
6 Local consequences of Acute inflammation
- swelling; in air spaces and in brain
- Inappropriate inflammation; hypersensitivity reaction
- exudation of fluid - can enter the pericardial space
- prolonged pain and loss of function
- digestion of host tissues by harmful enzymes released by neutrophils
- The cardinal signs
A systemic consequence is pyrexia - how does it occur?
Pyrogenic cytokines (TNF and IL-2) are released from macrophages and neutrophils, they act on the anterior hypothalamus increasing the synthesis of prostaglandins - which increase Body temperature
How does the body undergo leucocytosis following acute inflammation
Macrophages and endothelial cells secrete colony-stimulating factors so the BM produces more leukocytes
-IL-1 and TNFa accelerate the release from the BM
What kind of leukocyte would you primarily see in…
a) bacterial infection
b) viral
a) neutrophils
b) lymphocytes
What does the test C reactive protein do
Made and released from the liver during acute inflammation and can be measured to suggest if an infection is present
In the acute phase response in the liver, what are 3 constitutional symptoms, some acute-phase proteins and why you have lower protein synthesis
Constitutional symptoms: malaise, anorexia and nausea
Acute-phase proteins: CRP, fibrinogen, alpha1antitrypsinm, haptoglobin, serum amyloid A protein
Dropped albumin level in the blood as the body is trying to fight off infection
Explain the normal sequelae of acute inflammation
Resolution; mediators and neutrophils have short half-lives and degrade quickly.
- Stimulus is removed
- Exudate drains into lymphatics
- Fibrin is broken down by a thrombolytic process
- replacement of injured cells
Name 3 abnormal results of acute inflammation
- Suppuration - excess exudate, can form pus and abscesses
- Chronic inflammation - granulation tissue, fibrous scar and angiogenesis
- Death
What walls off abscesses
Pyogenic membrane
What dangerous locations can exudate accumulate?
Ascites: an abnormal buildup of fluid in the abdomen
Pleural and Cardiac cavity - fibrous exudate can cause the lung to stick to the pleural wall and the patient may have a sharp pain on breathing and cardiac impairment
What is hereditary angioedema and 2 consequences
Autosomal dominant, deficiency of C1 esterase inhibitor that inhibits bradykinin, family history of sudden death
Can have a:
1. Non-itchy cutaneous angioedema - deep skin buildup of fluid
2. Intestinal edema - abdominal pain as intestine can swell up
What is alpha 1 antitrypsin deficiency and 2 consequences
Autosomal recessive
Low levels of A1AT means you don’t have a protease inhibitor - therefore inflammation goes unchecked
Can have a…
1. Emphysema: Type of COPD as breathing tubules are narrowed and air sacs damaged
2. Cirrhosis: liver doesn’t function properly due to excessive ECM and collagen break down
SO when someone is aged 40-50 with liver cirrhosis and has minimal alcohol consumption consider this disease
What is chronic granulomatous disease? What are the consequences?
Defect in neutrophil function, the neutrophil is unable to generate superoxide and can’t kill the bacteria.
- Chronic infections from the first year of life
- Abscesses: caused by a bacterial infection
- Granulomas: a mass of granulation tissue typically produced in response to infection, inflammation or presence of the foreign substance
