Inflammation
Medicine Smd 535 with Koles at Wright State University
About this deck
By: Anonymous
Textbook:
Robbins & Cotran Pathologic Basis of Disease: With STUDENT CONSULT Online Access (Robbins Pathology)
Created: 2011-08-17
Size: 45 flashcards
Views: 21
Textbook:
Robbins & Cotran Pathologic Basis of Disease: With STUDENT CONSULT Online Access (Robbins Pathology)Created: 2011-08-17
Size: 45 flashcards
Views: 21
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Inflammation Def
Response when blood vessels react to injury/damage. Leads to accumulation of fluid, protein, and activated WBCs
Inflammation benefits
- Eliminates cause of injury - organisms, toxin etc
- Removes necrotic cells
Inflammation Harms
Destroys Host tissue
Causes fibrous scarring and decreased function
Acute Inflammation
- Seconds-Minutes, PMNs dominate, Edema, complete Resolution
Chronic Inflammation
- Days-Weeks, Macrophages and lymphocytes dominate, Repair processes, Does not completely resolve → leaves scar
Inflammation components - 3
- Dilation of blood vessels
- increases flow
- Microvasculature changes
- allow water, plasma, cells, and protein to leak out - exudate
- PMN migration - to site of injury
Vascular changes - 3
- Vasodilation - secs
- Arterioles → capillaries → venules → increased blood flow: red/heat
- Increased Permeability - mins
- For capillaries and venules - allows protein through → exudate
- Increases viscosity → stasis - slowing of blood
- PMN diapedesis - min-hrs
Vascular Permeability Increases - 4
- gaps in venules from Retraction
- Histamine, Complement
- Friendly fire from PMNs in arterioles, caps and venules
- Leukocyte adhesion to vens and caps
- venule leakage channels
Transmigration Site
PCVs
Selectin binding site
Leukocyte sialylated oligosaccharides
Selectins on the endothelium
ICAM Binding site
Leukocyte integrins
ICAMs on endothelium
Endothelium activation - 2 Mediators
- IL1 TNF induce expression of selectins on endothelium
- Histamine and Thrombin redistribute Weibel palade body selectins
PMN activation - 3 steps
- activated by chemokines
- increased integrin avidity → bind ICAM1 CD54 on endothelium
- migrate w pseudopods and CD31 PECAM-1
- Also on endothelium
Chemotaxis: 3 endogenous
- locomotion along a chem gradient
- Exogenous
- bacterial products
- Endogenous
- C5a, Leukotriene B4, Cytokines
PMN Activation Outcomes
- G-Coupled
- Increased avidity → endothelium adhesion
- Chemotaxis
- TLRs
- Production of mediators
- Amplification → overabundance
- ROS
- Phagocyte Receptor
- Phagocytosis and killing via ROS
Phagocytosis
- Attachment - phagocyte receptors/opsonins
- Engulfment
- pseudopods flow around → create phagosome
- Killing
- merging of phagosome and lyso → phagolysome
- Kill: MPO, ROS, NO
O2 Dependent Killing
- Makes H2O2 - toxic but not very cidal
- MPO - in azurophillics
- Converts H2O2 → OCl radical
- OCl destroys via halogenation - effective as hell
O2 Independent Killing - 4
- BPI - Bacteriacidal Permeability Increasing Protein - Azure
- Lysozyme (cell walls)- Azure
- Major Basic Protein - Eosinophil
- Acid Hydrolase - Azure
Acquired Immune Defects
- Marrow suppression - decreased leukocytes
- Diabetes, neoplasia, sepsis, dialysis - adhesion and chemotaxis
- Leukemia, anemia, sepsis, diabetes, malnutrition, premies
- phagocytosis and cidal activity
Chemicals in Cells - 3
- Histamine, Serotonin, Lysosomal enzymes,
Cell made Chemicals - 4
- prostoglandins/leukocytes, NO, cytokines, ROS
Chems from Liver - 2
- Factor 12
- Kinin
- Coagulation/fibrinolysis system
- Complement system
PMN Granules
- Azurophilic Granules - Primary
- MPO - cidal
- Specific - Secondary
- No peroxidase
- Contain Lactoferrin
- Exrtracellular effects
- increases permeability, damage, chemotaxis
Vasoactive Amines - 2
- Histamine
- Mast Cells, basophils, platelets
- Injury, Immune rxn, C3a C5a, IL1 IL8
- Binds H1 receptor - s muscle and endothelium → dilation and increased perm
- Serotonin
- Platelets, DNES
- Like histamine
Complement
- Cell lysis
- MAC attack!
- C3a C5a - anaphylaxins
- increase vascular perm, release histamine from masts
- C5a PMN chemotactin (also other WBCs)
- C3b - opsonin
Clotting System
- Thrombin - links coagulation and inflammation
- binds protease activated receptors (PAR)
- Thrombin + PAR1 binding → inflammatory response
- Factor Xa
- Increases perm
- Factor XIIa
- activates fibrinolysis → plasmin → C3 → C3a...
- Kinin - from XII
- makes bradykinin
IL1 and TNF
- Local
- endothelium activation
- adhesin expression
- procoag and inti coag
- Leukocytes
- activates, produce cytokines
- Fibroblasts - proliferation, collagen
- Systemic
- Fever, leukocytosis, seepy
NO
- Relaxes smooth muscle
- Made by
- Endothelials, Macros, brain
- Stimulated in endothelium - by cytokines TNF IFNy
- low constituitive in endothelium
- Paracrine effector - makes cGMP
- Toxic to microbes
- Too much prevents rolling - decreases recruitment
Vasodilation - 3 mediators
- Prostoglandins
- NO
- Histamine
Increase Perm 5 Mediators
- Histamine
- Serotonin
- C3a C5a
- Leukotriene
- substance P
Chemotaxis & PMN activation 5 Mediators
- TNF IL1
- Chemokines
- Complement
- Leukotriene B4
- Bacterial products
Fever - 2
- IL1, TNF
- prostoglandin E2 in hypothalmus
Pain - 2
- prostoglandins
- Bradykinin
Acute Inflammation Outcomes
- Resolution
- Abscess
- FIbrosis
- Chronic Inflammation
Chronic Inflammation
- Inflammation for prolonged duration - weeks to years - cellular infiltrates, tissue destruction and repair all happens at once
Macros
Activation
Short lived
- IFN-y from CD4s and NKs
- Endotoxins
Short lived
- Apoptose - lymphatic clearance
- Focus → granuloma
- Recruited via chemotactic factors
Lymph System and Inflammation
Drain extracellular fluid into venous blood
- Lymphangitis - inflammation of regional channels
Red streaks on skin - drain local focus - Lymphadenitis - inflammation of regional lymph nodes
Serous
Watery: Bullous Pemphigoid
Fibrinous
Shaggy - on heart after MI
Fibrinogen escapes → fibrin covers surfaces
Fibrinogen escapes → fibrin covers surfaces
Ulcer
Local defect in surface of an organ from sloughing off of necrotic tissue damaged by inflammation
WBC Test
- Leukocytosis is over 10k
- shift to the left - bands
- Neutrophilia - bacterial
- Lymphocytosis - viral
CRP Test
CRP > 8 mg/dl
- Upregulated by IL6 - made in liver
- Increases w/in 6hrs of inflammation
- More sensitive than sedimentation rate
- Does not show cause
RBC Sedimentatio
RBC Sedimentation < 20mm/hr
- Less sensitive than CRP
- No Cause
Prostoglandins - 5
Cell Made
Pain & Fever
Vasodilation
Vascular Permeability
Chemotactic for PMNs
Plasmin
- Kinin Product
- Fibrin Split products
- pro-inflammatory
- Activates Complement
About this deck
By: Anonymous
Textbook: Robbins & Cotran Pathologic Basis of Disease: With STUDENT CONSULT Online Access (Robbins Pathology)
Created: 2011-08-17
Size: 45 flashcards
Views: 21
Textbook:
Robbins & Cotran Pathologic Basis of Disease: With STUDENT CONSULT Online Access (Robbins Pathology)Created: 2011-08-17
Size: 45 flashcards
Views: 21
About StudyBlue
STUDYBLUE makes things that make you better at school.
Things like online flashcards with photos and audio.
Things like personalized quizzes and friendly reminders about when (and what) to study next.
Think of it as a digital backpack™: access to all of your study materials online and on your phone.
STUDYBLUE exists to make studying efficient and effective for every student, for free. Join us.
“I have been getting MUCH better grades on all my tests for school. Flash cards, notes, and quizzes are great on here. Thanks!”
Kathy
Kathy