Final stuff lecture 1-20

Question 1

transfusion related acute lung injury

Answer 1

• 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

Question 2

What does protein C inhibit? what is it activated by?

Answer 2

inhibits factor 5, 8 , activated by thrombin

Question 3

What does antithrombin inhibit

Answer 3

-switches of activated 10, 9, 11, and prothrombin

Question 4

How does heparin work?

How does dabigatran work?
-what revereses this?

how can you tell between then?

Answer 4

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

Question 5

3 reasons why

What does it mean when there is a prolonged APTT and a prolonged 1 + 1?

Answer 5

1. lupus anticoagulant - (no bleeding), but can alter APPT lab test
2. Autoimmune disease- (bleeding) can make antibodies against some clotting factors
3. Drugs - slow down clotting e.g heparin, dabigatran

Question 6

Multiple factor deficiencies cause

Answer 6

• 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

Question 7

What is most sensitive test for liver disease?

Answer 7

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

Question 8

Prolonged PT causes

Answer 8

• extrinsic pathway
• wafarin - 2,7,9,10
• vit K deficiencey
• liver disease
• low factor 7 (but this is only if APPT is normal)

Question 9

How to monitor wafarin

Answer 9

• 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

Question 10

What does wafarin do?

• when is it used?
• how to reverse?

Answer 10

• 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

Question 11

risks VT

Answer 11

-trauma, surgical manipulation, prior thrombosis, atherosclerosis

immobility - post op, plane
Pressure - (blockages) catheter, tumour obstruction
Increased viscosity - polycthaemia, dehydration, EPO

Question 12

Inherited Thrombophilia

Answer 12

-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

Question 13

To learn for exam

Answer 13

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

Question 14

direct acting oral anticoagulants

low molecular weight heparin

Answer 14

-will reverse 10a - no effect on APPT

Question 15

Streptococcus pyogenes
2 virulence factors
2 diseases

Treatment

Answer 15

• 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) ,

Question 16

Staphylococcus aureus
2 virulence factors
2 diseases

Treatment

Answer 16

• 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

Question 17

How to test these skin infections

Answer 17

• take a pus swab from area
• take to lab
• if in hospital - also take a blood sample

Question 18

enzyme penicillin works on

Answer 18

transpeptidase

Question 19

Risk factors for osteomylitis

Answer 19

• chicken pox can lead to SSTI can get osteomylitis

- surgery, trauma ect.

Question 20

What is signal 2 for an antigen presenting cell

Answer 20

ICAM 3 - on APC, matches with LFA -1 on t helper cell

Question 21

Main points about septic arthritis

Answer 21

• 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

Question 22

Staphylococcus pyogenes - lab test

Answer 22

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

Question 23

Staphylococcus pyogenes - lab test

Answer 23

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

Question 24

Staph aureus - lab test

Answer 24

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)

Question 25

Streptococcus pneumonia - what it causes?

lab test

Answer 25

-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

Question 26

Effect of warfarin, heparin, dabigatran, rivaroxabn on APPT, PT, TCT

Answer 26

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)

Question 27

3 disorders of pulmonary or systemic innate immune system that might contribute to bronchiectasis

Answer 27

Bornchiectasis - is a viral infection

-May have reduce t cells - cannot get repsonse working as well

Question 28

how does erythropmycin work?

Answer 28

Erythromycin (macrolide) inhibit bacterial protein synthesis by binding to 50S subunit of ribosome and blocking transpeptidation

Question 29

peritonitis - what to grow

treatment

Answer 29

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

Question 30

chemotherapy

Answer 30

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.

Question 31

when to give G-CSF

Answer 31

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.