4.1 Cardiac Electrophysiology and Arrhythmias Flashcards
Other than the endocardium, what other structures can be involved in endocarditis?
- Chordae tendinae
- Cardiac devices
- Interventricular septum
What are the names of lesions that characterise endocarditis? What do they contain?
- Vegetations
- Mass of platelets, fibrin, and inflammatory cells
Most common/less common causes of myocarditis
- Most common: viral
- Others: other infections, toxins, vaccines
Effect of myocarditis on cardiac enzymes and inflammatory markers
- Raised cardiac enzymes
- inflammatory markers
Most common cause of pericarditis (hint: it’s the same as that of myocarditis)
Viral infection
List some less common causes of perdicarditis (i.e. other than viral)
- Bacterial
- Uraemic
- Ischaemic
- Malignancy
- Radiation
Pericarditis ECG changes
ST elevation (this is why we need to be careful when diagnosing STEMI)
Which three types of fluid can cause pericardial distension?
- Serous
- Blood
- Pus
Acute vs chronic pericardial distension
- Acute: Can be very bad; compressing blood vessels and even ventricles, resulting in cardiac tamponade
- Chronic: pericardial space dilates, allowing slow accumulation of fluid
Which tissues are inflamed during serositis?
Serous tissues, pleura, pericardium, peritoneum
Common treatment of pericarditis
- NSAIDs (e.g. aspirin, ibuprofen)
- Corticosteroids
- Immunosuppression
What is an immune complex?
The molecule formed by the binding of a SOLUBLE antigen to an antibody (i.e. the antigen is not connected to another cell)
List some common clinical signs of infective endocarditis
- Osler’s Nodes
- Janeway lesions
- Splinter hemorrhages
- Roth spots
Outline the pathophysiology of infective endocarditis.
- Endothelial damage occurs to endocardium (e.g. due to turbulent blood flow)
- Platelets and fibrin adhere to damaged surface
- If bacteremia is occuring, then some bacteria may bind to these platelet-fibrin complexes, forming vegetations
- Vegetations can produce septic emboli, which travel throughout the body
What is type 3 hypersensitivity also known as?
Immune Complex Disease
What is an Arthus reaction?
Localised immune complex mediated hypersensitivity reaction of dermal blood vessels
Why don’t immune complexes cause type 3 hypersensitivity reactions when antibodies are present in roughly equal proportion to antigens? What is this called?
Because the immune complexes form a lattice, and can be removed by mononuclear phagocytes.
This is known as “equivalence”
Describe the four common steps of the inflammatory response
- Cell surface pattern receptors recognize detrimental stimuli
- Inflammatory pathways are activated
- Inflammatory markers are released
- Inflammatory cells are recruited
Describe how surface receptors lead to activation of inflammatory pathways and release of cytokines
- Ligand binds to receptor
- Leads to increase transcription and translation of inflammatory cytokines
- Cytokines either recruit other inflammatory cells, or have a direct effect
What are the four main receptor pathways by which the inflammatory response can be triggered?
- Pattern recognition receptors
- NF-kB pathway
- MAPK pathway
- JAK-STAT pathway
What does it mean that cytokines are pleiotropic?
They can exert multiple different types of cell responses, often on different cell types
What does it mean that cytokines are redundant?
If one cytokine is inactivated, others can step in an do its job (much the same as coronary autoregulation)
How can cytokine redundancy reduce treatment effectiveness?
If a medication inactivates a single cytokine, then - over time - others may take its place, and so the underlying pathology will remain.
Are all cytokines elevated in all diseases at the same time?
No.
They are all elevated in all diseases at different times!
Why is it important to understand that cytokines can be clustered into groups?
Because, depending on the specific inflammatory pathway, T helper cells will release different cytokines, helping you to localise the source of inflammation.
Why is it clinically important that different cytokines are released at different stages of “a” disease?
Because one drug may not work for every patient, and it will not work for the entire duration of a disease.
How does strep A most commonly manifest in terms of disease presentation?
- Pharyngitis
- Tonsillopharyngitis
List some major clinical features of Acute Rheumatic Fever
- Carditis & valvulitis
- Arthritis
- Erythema marginatum
How do M proteins on streptococci cause autoimmune complications?
- M protein is similar to proteins in glomeruli, valvular tissue etc.
- Therefore, the body may mistakenly misdirect the immune response towards itself
Effect of M protein on complement system and phagocytosis
Decrease/inhibit
Describe the diagnosis of streptococcal infection
- The bacteria may be cultured using a throat swab or blood samples
- Alternatively, specific antibodies may be measured using enzyme-linked immunosorbent assay (ELISA)
Describe how molecular mimicry may enable pathogens to cause autoimmune issues
- Antigen presenting cells (e.g. dendritic cells) present foreign peptide (which “mimics: endogenous proteins) to T cells
- Leads to B cell activation, producing antibodies that may mistakenly bind to endogenous proteins, thus causing an autoimmune response
Describe how bystander activation may enable pathogens to cause autoimmune issues
- Inflammatory response is mounted to correct antigen as usual
- Leads to activation of immature dendritic cells that present self-peptide
- Leads to autoimmune response
What percentage range of strep A patients developed ARF?
0.05-0.1%
What is the main class of factor that influences an individuals risk of developing ARF after Strep A?
- Genetic differences
- (there are others)
Describe an alternative pathogenesis for rheumatic fever involving the basement membrane.
- Strep A bacteria use their M proteins to bind to collagen in the basement membrane
- Creates an immunogenic neoepitope
- Leads to autoimmune response against collagen, thus influencing factors throughout the body (including heart muscles)
Provide a super basic pathogenesis of acute rheumatic fever
- Strep A infection
- Invades epithelium (most commonly upper resp)
- Foreign Strep A antigens are detected, and the body mounts an immune response
- Antibodies bear structural similarity to autonantibodies that could bind to certain self tissues
- This can lead to damage of skin, brain, joints, and heart
Describe the pathogenesis of inflammatory heart disease in ARF
- GAS antibodies bind to endothelial surface
- Leads to activation of VCAM1, leading to adherence of T cells
- Subsequent inflammatory response leads to endothelial damage and valve remodelling
What is chorea?
Chorea is a movement disorder that causes involuntary, irregular, unpredictable muscle movements.
Pathogenesis of chorea
- Basal ganglia neurons targeted by cross reactive GAS antibodies
- Alters intrracellular signalling pathways, leading to increased activity of tyrosine kinase
- Leads to increased dopamine production and secretion, causing abnormal movements or behaviours
Pathogenesis of arthritis in rheumatic fever
Cross-reactive antibodies bind to synovium, causing localised inflammation and pain.
Pathogenesis of erythema marginatum/subcutaneous nodules (they are different)?
Erythema marginatum: cross-reactive GAS antibodies bind with keratin
Subcutaneous nodules: granulomatous lesion (accumulation of white blood cells)
