Final stuff lecture 1-20 Flashcards
transfusion related acute lung injury
- onset of acute lung injury within 6 hrs transfusion
- donor plasma contains whit cell antibodies leading to aggultination and sequestion of recipient nuetrophils in pulmonary vasculature
What does protein C inhibit? what is it activated by?
inhibits factor 5, 8 , activated by thrombin
What does antithrombin inhibit
-switches of activated 10, 9, 11, and prothrombin
How does heparin work?
How does dabigatran work?
-what revereses this?
how can you tell between then?
Heparin
- up regulates antithrombin - so will mean clotting will slow down
- (antithrombin - blocks thrombin, 10, 9, 11)
- bleeding history
- long APPT, 1+ 1 and TCT
Dabigatran
- directly inhibits thrombin
- very sensitive to TCT
- reversible by - idarucizumab
Protamine will reverse heparin
3 reasons why
What does it mean when there is a prolonged APTT and a prolonged 1 + 1?
- lupus anticoagulant - (no bleeding), but can alter APPT lab test
- Autoimmune disease- (bleeding) can make antibodies against some clotting factors
- Drugs - slow down clotting e.g heparin, dabigatran
Multiple factor deficiencies cause
- vit K/ warfarin
- blood loss - missing all and missing platelets
- DIC - disseminated intravascular coagulation -widespread activation of coagulation which causes thrombin followed by bleeding as clotting factors and platelets are used up
- Liver disease - makes clotting components
What is most sensitive test for liver disease?
Liver disease - lack of production of coagulation factors and inhibitors (except 8) - all are made in liver except 8
-prothrombin assay most sensitive to liver disease, because vit K factors get used up first and billary system is most common in this disease
Prolonged PT causes
- extrinsic pathway
- wafarin - 2,7,9,10
- vit K deficiencey
- liver disease
- low factor 7 (but this is only if APPT is normal)
How to monitor wafarin
- Using PT ratio
- use INR - international normalised ratio
- this standardises the prothrombin ratio, so that if you measure the INR in any lab it will be the same
- APPT also prolonged with warfarin, but not to the same extent and dont routinely measure it
What does wafarin do?
- when is it used?
- how to reverse?
- inhibits recycling of vit K
- cannot get coagulation factors to stick onto platelets
- if give a big dose of Vit K - can overcome wafarin
- used in atrial fibrillation, venous thromboembolism, other thrombotic disorders
risks VT
-trauma, surgical manipulation, prior thrombosis, atherosclerosis
immobility - post op, plane
Pressure - (blockages) catheter, tumour obstruction
Increased viscosity - polycthaemia, dehydration, EPO
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 APCR gene
APCR - heteroyzgous - increased risk
-homozygous - very large increased risk
Absolute risk - most important
To learn for exam
changes of DVT being spontaneous vs provoked
- 30-40% spontenous (50% of these are inherited)
- rest are provoked
Risk factors for VTE
Heriditary thrombophilia - treat with anticoagulation
Need to know the effect of the drugs on the clotting tests
direct acting oral anticoagulants
low molecular weight heparin
-will reverse 10a - no effect on APPT
Streptococcus pyogenes
2 virulence factors
2 diseases
Treatment
- adhesion factors - can adhere to ecm to further infect cells
- capsule - hyuloronidase to prvent opsonisation and phagocytosis
- M protein - binds to factor H , prevents opsonisation by c3b
- streptokinase - anticoagulant can break down clot - degreades fibrin and can further get out
disease
- rheumatic fever
- SSTI
- septic arthritis
- pharyngitis
treatment - penicillin, flucoxacyllin, amoxycillin (beta lacatamse resistant) ,
Staphylococcus aureus
2 virulence factors
2 diseases
Treatment
- slime layer - makes polysacharide layer to build up layers of bacteria underneath and protect them (prevent opsoinsaiton and phagocytosis)
- clumping factor - can bind fibrinogen, get a clot around it so that it can avoid phagocytosis and opsonisation
Disease
- Osteomyelitis
- toxic shock syndrome
- septic arthritis
- methicilin - cannot be destoryed by b-lactamase
- penicilin combined with b-lactamase inhibitor
- or amoxicilin + claulanic aice
- however can get menicillin resistant staph - give vancomycin
How to test these skin infections
- take a pus swab from area
- take to lab
- if in hospital - also take a blood sample
enzyme penicillin works on
transpeptidase
Risk factors for osteomylitis
- chicken pox can lead to SSTI can get osteomylitis
- surgery, trauma ect.
What is signal 2 for an antigen presenting cell
ICAM 3 - on APC, matches with LFA -1 on t helper cell
Main points about septic arthritis
- needs to be diagnosed quickly as early treatment prevents complications such as irreversible damage from growth plate disruption
- ealry diagnosis is hard to see
- knee, hip and ankle most common joints
- 2 most common - staph aureus and streptococcus pyogens
- drainage and wash out of septic joint is often needed for diagnosis and treatment
- IV antibiotics are needed initially and total corse is likley to be 2-3 weeks
Staphylococcus pyogenes - lab test
lab -head smear bacteria
- gram stain (positive)
- grow on horse blood agar (beta haemolysis - clear)
- bacitracin sensitivity - sensitive - is s.pyogenes
- confirm with streptococcus grouping test
Staphylococcus pyogenes - lab test
lab -head smear bacteria
- gram stain (positive)
- look at shape of bacteria on slide (coccus)
- catalyse test - negative
- grow on horse blood agar (beta haemolysis - clear)
- bacitracin sensitivity - sensitive - is s.pyogenes
- confirm with streptococcus grouping test
Staph aureus - lab test
lab - heat smear bacteria
- gram stain (positive)
- look at shape of bacteria - coccus
- catalase test (positive)
- coagulase test (positive)
- then is staph aureus
(if grown on MAC plate - turns it yellow)
(if grown on blood agar - beta haemolysis)
Streptococcus pneumonia - what it causes?
lab test
-causes upper resp tract infection
lab -head smear bacteria
- gram stain (positive)
- look at shape of bacteria on slide (coccus)
- catalyse test - negative
- grow on horse blood agar (alpha haemolysis - green)
- optochin sensitivity - is sensitive
Effect of warfarin, heparin, dabigatran, rivaroxabn on APPT, PT, TCT
Warfarin – PT prolonged, APPT norm, TCT norm
Unfractionate heparin – APPT prolonged, PT – norm, TCT – prolonged
Dabigatran – APPT – prolonged, PT –norm , TCT – prolonged
? Rivaroxabn - APPT and PT prolonged, TCT normal (works on factor 10)
3 disorders of pulmonary or systemic innate immune system that might contribute to bronchiectasis
Bornchiectasis - is a viral infection
-May have reduce t cells - cannot get repsonse working as well
how does erythropmycin work?
Erythromycin (macrolide) inhibit bacterial protein synthesis by binding to 50S subunit of ribosome and blocking transpeptidation
peritonitis - what to grow
treatment
D. Gram stain: pink (gram neg) rods, possibly gram pos (purple) cocci and after culturing on bile esculin for fastidious bacteroides more gram neg (pink) rods
E. MacConkey agar for E.coli and enterococci: selective growth of gram neg intestinal pathogens and enterococci. Bile salts inhibit growth of non-enteric bacteria. Differential for lactose-fermenting bacteria. Bile esculin agar for Enterobacteriaceae, Bacteroides fragilis and enterococci: selective and differential agar for isolation of enterococci/group D streptococci. Bile salts are selective and esculin is differential for esculin hydrolysis
G. Treatment of bacterial cause: empiric, broad spec to begin with to eliminate hypothesised polymicrobial infection. Triple therapy: aminoglycoside (gentamycin) for E.coli, nitroimidazole (metronidazole) for Bacteroides and penicillin (ampicillin) for enterococcus. Consider single therapy (dependent on culture) for liver/kidney failure patients to reduce amount of antibiotic having to be cleared
chemotherapy
C. Chemotherapy causes a decrease in White Blood Cell count. This leaves the patient being treated for Acute Myeloid Leukaemia at a much greater risk of infection and bacteraemia therefore a fever in this patient is of great concern and can very quickly lead to severe or even fatal outcomes. This risk is investigated through blood cultures of central and peripheral lines, swabbing the skin and oral mucosa as well as a chest x-ray to examine for infection in either the respiratory or cardiovascular systems. A febrile, neutropenic patient is managed by immediately starting them on a course of broad spectrum antibiotics (Tazocin and Gentamicin) because of how quickly their condition can deteriorate in this situation.
when to give G-CSF
Risk can be reduced through the administration of G-CSF after chemotherapy which has been shown to reduce the severity of the neutropenia: definitely administer if risk of FN >20%, maybe if 10-20% and probably not if <10%.Risk could also be reduced by decreasing the intensity of the chemotherapy being administered but doing so also reduces the efficacy of the chemotherapy itself.
