Lecture - Infection and Immunity - Infective Endocarditis

Question 1

Okay so let’s start with the basics:

Bacteraemia

1. What is it?
2. Secondary to what at where?
3. Is it long term or transient? How is it removed?
4. But it can cause disease in who? What’re three examples of infections that come from bacteraemias

Septicaemia

1. ______ bacteri/bacterial products in blood
2. Is it pathological or physiologica?
3. So if it’s pathological, what does that mean? It’s u____, g_____, i______ r_______ so it’s pro inflammatory aka things like DIC, embolism, thrombosis, ischaemia, necrosis
4. Is it nicely or poorly defined clinically? So what’s is septicaemia replaced by the concept of?

Answer 1

So like bacteraemia is when it’s j chillin in your blood and in septacemia, it’s pathological so it’s pro-inflammatory so like, you’ll provoke an immune inflam reponse and it’s totaly inappropriate

Question 2

5 stages of sepsis

Okay so, what are they? Describe them to me

Answer 2

Alrighty so you have the systemic inflammatory response syndrome (SIRS) first and that’s if you have 2 or more of:

• hypo/hyperthermia
• tachycardia
• tachypnoea
• Increased WBC/immature PMNs (since you have inflammation, you have immature neutrophils_

So SIRS can happen with any sort of inflammation, not just microbial stuff like it can even with cancer. But it is the first thing you use to recognise people who might be septic. The clinical criteria is that you need to have two or more of those to have SIRS

After that, you get sepsis. This is when you have 2 or more SIRs criteria AND a proven infection like a positive blood culture/gram stain/PCR. So most are bacterial but it can be fungal and virus too.

Then you get severe sepsis - this is when things are starting to go wrong like your BV will dilate and become leaky so you’ll have volume lost in tissue - so shows in organs and you can see that they’ve got severe sepsis. Basically, this is when you have sepsis and cardiac dysfunction with hypotension and hypoperfusion leading to organ dysfunction.

Then you get the septic shock. This is severe sepsis + organ dysfunction despite fluid resuscitation. So the function of organs aren’t recovering even if you’re trying to replace the fluid (organ dysfunction even with fluid resuscitation)

Finally, you have multi-organ dysfunction syndrome (MODS) where you have organ failure due to hypoxia. There is a direct correlation between the number of organ systems failed and mortality. Any organ can be involved - they’re failing bc they aren’t perfused.

As you go further down into the stages of sepsis, you increase the severity and risk of mortality.

Question 3

Blood culture - gold standard

1. So is blood sterile or not usually? What does that mean if you have some sort of bac or fungi present? What if you find skin microbiota in your blood culture - where could it have come from?
2. What is the most common reason samples are taken? Should you take them before or after emperic therapy?
3. There is an increased chance of isolating organisms if you have how many sets? How often should you take the sets?
   - what does a set consist of?

Question 4

Infective endocarditis (IE)

1. Infection of what two things?
   - you’ll get formation of what (this can hapen on native/prosthetic valves or even pace makers)
2. There is acute and subacute (short and long incubation respectively). What’re each like in terms of:
   - time course
   - target what sort of valves (normal or damaged ones)
   - what sort of pathogen in terms of virulence
   - treatment with antimicrobials
   - mortality

Question 5

Aetiology

1. Which organism is known to target native valves acutely?
2. What about the one that targets prosthetic valves?
3. What low virulence organism that lives in your oral microbiota is the most common cause of subacute IE?
4. If you have a blood culture that’s negative but you know there is sepsis, what group is it likely to be? They’re more common in children
5. Fungi also like prosthetic valves - true or false?

Question 6

So infective endocarditis is hard to diagnose so you should know the risk factors involved:

1. What age roughly is it mroe common on?
2. What sex is it more common in?
3. What sort of disease will
4. Having this is what staph epidermidis (and staph aureus!) like to make biofilms on
5. If you’re i______ (the most logical risk factor)

Answer 6

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Question 7

Clinical signs of IE

1. What’s the most common sign? It’s intermittent and low grade (might even be absent) in subacute though
2. New or changing m______
   - should you just exlcude them if they don’t have this?
3. Is it easy or hard to diagnose?

Question 8

Complications

Often presenting symptoms:

1. What would you see in cardiac if you have IE?
2. Neurological
3. Spetic emobli can lodge where? What even is septic emboli?
4. Infection but what kind?
5. What’s the fancy word for renal failure - why does this one happen?

Answer 8

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Question 9

Pathogenesis

1. SO bacterial/platelet interaction is critical - explain this
2. Describe the pathogenesis of subacute endocarditis
3. What happens with the vegetative growths?
4. How are virlence bacteria that cause acute IE different to subacute?
5. What’s device-assocaited endocarditis?

Answer 9

1. Okay so you have the bacteria in the blood and the bacteria will bind to receptors on the platelets since they have adhesion molecules. When they bind, you’ll have the activation of the platelets (upregulate expression of more receptors and fibrinogen is binding to platelet integrins) and you will see coagulation and more activation and then more get recruited so you get fibrin clots that contain more bacteria. Remember, at this stage we’re just talking about the bacteria/platelet interaction being critical in the pathogenesis of iE
2. With subacute endocarditis, the mechanism of native valve is differnet. You have a damaged valve and then haemodynamics happens aka you’ll have deposition of platelets/fibrin (non bacterial thrombotic endocarditis). Then since you have bacteraemia, you’ll have adhesion of the bacterium to the platelet - this can be direct or through some bridging molecule. Then you have the formation of an infected thrombus and this is called a vegetation (so was sterile before but not anymore). This vegegation consists of platelets, fibrinm bacteria, inflammatory cells and it’s protected from neutrophils for some reason. SO if platelets activate then mroe platelets and fibrin are deposited
3. This is most common on heart valves (mitral and aortic). So te growth will mature and you’ll see more complications like bacteria can leave the thing and go into blood and cause bacteraemia or even sepsis or go to another organ and cause infection there. Big or small parts of the growth may be released and form septi emboli (since theyr’e infected). These emobi can go and occlude and lead to infarction/ischaemia and you can get a septic infarct. Also, the immune complexes (the AB plus the antigen complex) can travel to the kidney, get stuck and cause inflammation so you get renal failure (glomerulonephritis)
4. These will bind directly to the cell surface (with MSCRAMMS) and also SERAMS - these are adhesion molecules that allow it to bind without needing the damage that subacute ones need. They also release bacterial toxins and this can cause inflammation or cell death
5. So staph epidermidis and aureus both like prosthethic valves/pacemakers and form biofilms. So like, prosthetic valves just really give a platform for the platelets and fibrin to be deposited since it’s a surface and that forms a conditioning film and that’s the first thing to forming a biofilm - the organism binds to the conditioning film so like, could be months before you see symptoms

Question 10

Diagnosis

1. Okay so it used to be Jone’s Criteria but what is it now?
2. What do major criteria include?
3. What does minor criteria include?
4. What else is important? This pathology is suggestive of damage to heart

Question 11

Treatment of IE

1. So you have initial treatment which is e_____
   - based on what?
2. What happens if IE is a biofilm infection?
3. What do you give if it’s a staph? What if it’s MRSA/S. epidermidis?
4. What do you give if you have streps?
5. What do you do with surgery?
6. Should we give prophylaxis?

Answer 11

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Question 12

Rheumatic fever and IE

1. It’s a _____ _________ process - sequale to what?
2. So 95% of RF is in the devleoping world but what are the risk groups in developed countries?
3. Generally affects which year group?
4. What’s the pathogeneiss of RF?

Rheumatic heart disease

1. What is this the most serious complicaion of?
2. What is endocarditis? What can it result in?
3. RHD can result from repeated inflammating and healing - what can that cause? (S____ and f_____)
4. Risk for i_____ e_____

Question 13

Go read the flow diagram on slide 24