Lecture 11- 15 overview Flashcards
What do neutrophils do when recognise PAMPs
what are 2 cells that recognise this
-they phagocytose the material with Pamps
neutrophils and dendritic cells
What are 3 things phagocytosis is promoted by?
neutrophils have receptors for …
- PAMPS
- C3b complement component
- Fc region of antibodies
What do actue phase proteins do?
- promote resolution and repair of inflammatory lesions
- limit tissue injury (e.g inhibit bacterial enzymes)
- enhance host resistance
- can also activate complement cascade
What is involved in innate immunity?
Physical barriers to infection - e.g skin
Microbial factors - lysozymes, complement
Phagocytic cells - neutrophils, macrophages
How is material digested endogenously and exogenously
Exogenous - phagocytosed material, acidification then protease degradation
Proteosome chops it up into peptide fragments and thes go onto cell surface, then it buds off and fuses with cell membrane
what are the 2 antigen presenting cells?
- dendritic cells
- b cells
Lecture 12 - go over al cue cards again
Lecture 12 - go over al cue cards again
Blood vessel injury
Flow of blood - changes
-trauma, surgical manipulation, prior thrombosis, atherosclerosis
immobility - post op, plane
Pressure - (blockages) catheter, tumour obstruction
Increased viscosity - polycthaemia, dehydration, EPO
Diagnosis of PE
classic symptom triad - pleuritic pain, shortness of breath, haemoptysis (blood in cough)
Signs - tachycardia, tacypnoea, hypoxia
Can do a CT scan
V/Q scan
- can die, or can get hypotension - need thormbolysis to break down the clot
- also can get see severe right heart strain due to back pressure from pulmonary arteries
Thrombophilia
-KEY LEARNING POINT - she said it was a hint
- what is it?
- what are the main causes?
- Tendency to develop thrombosis
- Can be acquired or inherited
- manifested as venous thromboembolism
- some spontaneous -have genetic increased risk
- some are provoked events - surgery or trauma, immobility, hospitalisation, malignancy, pregnancy
Inherited Thrombophilia
-abnormal inhibitor function - resistance to activated protein C (factor 5 leiden)
-Deficeincey of inhibitors - antithrombin , protien C, protien S
Increased factor levels - prothrobin gene mutation, elveated factor VIII
Factor V leiden
Factor 5a enhances factor 10 activation
- activated protein C cleaves normal factor Va
- slows Xa production
- so if have bad protein C then cannot get inactive factor 5 and keep getting the clot
- if factor V has this mutation then cannot get interaction with protein C as good, so results in it being increased - increased coagulation (cannot inactivate factor 5)
- may have helped survival in oldern days e.g not bleeding to death with pregnancy
APCr gene
-if have both carriers - then get a huge increase in risk of thrombosis
Treatment PE and DVT
Initially - heparin (IV)
Immediate effect
-heparin prolongs the APPT, antithrombin deficiency does not.??!
- heparin binds to antithrombin, and activates it
- antithrombin then inactivates thrombin, factor 10a
-causes APPT 1 + 1 and tct to be increasde
reversed with protmine (harder to reverse low molecular weight heparin)
low molecular weight heparin
- inhibits 10a (dont test with APPT)
- subcutaneous better bioavailability
- come in prepackaged vials
- Enoxaparin 1mg/kg twice daily
- dont use appt to measure low molecular weight heparin
-basically are changing the bodys mechanisms around so can get clotting
Treatment plan VTE
-low molecular weight heaprin
-wafarin (7,9,10)
-
-inhibits coagulation, allows own fibrilitc mechanims to operate unhindered by further clotting
Wafarin
- interacts with a lot of things e.g antibiotics,
- higher INR increases bleeding risk further
- takes a days to work as there will still be active clotting factors in the blood
- keep giving low molecular weight heparin till this works
- want an INR of 2-3
Bleeding on warfarin
vit K IV
-however takes 12-24 hours for the clotting factors to be made
-if need immediate reversal - have prothrombinex which contains 2, 9, 10
Direct acting oral anticoagulants
- same as warfarin for treatment of VTE
- superior for anticoagulation in atrial fibrillation - better stroke prevention with similar rates of bleeding
- people with kidney failure can accumulate high levels of this
Rivaroxaban works on 10a and dabigatran works on thrombin
Advantages - no monitoring needed, fixed dose
-less intracrainal haemorrhage compared to warfarin
DIsadvantages- renal exrection retained with renal imparimed
Clotting tests and DOACs
- Dabigatran - TCT extremely sensitive
- Rivaroxaban - PR prolonged, APPT less so, wont effect TCT at all
- idarucizumab - is an antidote for dabigatran - it binds to it, almost immediately reverses this
Side effects after DVT
- 30% of DVT patients develop post thrombotic syndrome - pain, swelling/odema, redness, venous eczema, ulceration
- graduated compression stockings may help manage the symptoms of PTS
- 2% of PE patients may develop chronic thromboembolic pulmona hypertension
Inflammation response to bacterial infection
- what type of cells
- how are clots formned?
innate immune responses
-bacteria gets past skin barrier
-produces toxins, these damage tissues
-mast cells and macrophages become activated and send of further pro inflammatory cytokines and chemokines
(mast cells - release heparin and histamine) (macrophages can recognise PAMPs)
-vasodilation and increased permeability of blood vessels results
-nuertrophils can squeeze out of blood to site of infection
-platelets produce blood clots around bacteria to stop it getting into blood
-neutrophils fight the bacteria
PAMPS - can trigger proinflammatory cytokines
- Complement system activated in response to cell wall components on bacteria
- nuetrophils squeeze out of blood
Inflammation response to bacterial infection
- what type of cells
- how are clots formed?
innate immune responses
-bacteria gets past skin barrier
-produces toxins, these damage tissues
-mast cells and macrophages become activated and send of further pro inflammatory cytokines and chemokines
(mast cells - release heparin and histamine) (macrophages can recognise PAMPs)
-vasodilation and increased permeability of blood vessels results
-nuertrophils can squeeze out of blood to site of infection
-platelets produce blood clots around bacteria to stop it getting into blood
-neutrophils fight the bacteria
PAMPS - can trigger proinflammatory cytokines
- Complement system activated in response to cell wall components on bacteria
- nuetrophils squeeze out of blood
where is cellulitis found?
-Often seen around injury site or deep abscess
what is Necrotising fasciitis (flesh eating disease)
- Deep infection of skin, destruction of tissue and fascia
- development into severe systemic disease
- high mortality
treatment for SSTI
S.pyogenes
s,aureus
Penicilin , amyoxicilin
beta lactamase resistant penicilin - flucloxacillin (except for MRSA strains)
treatment for SSTI
S.pyogenes
s,aureus
Penicilin e.g amyoxicilin
beta lactamase resistant penicilin - flucloxacillin (except for MRSA strains)
