2. Epidemiology, Presentation & Diagnosis Flashcards
1
Q
ID: Environment
A
- Climate
- Geography
- Healthcare systems
- Exposure
- Social
2
Q
ID: Host
A
- Symptoms
- Immunity/Susceptibility
- Risk behaviour
- Lifestyle
3
Q
ID: Pathogen
A
- Virulence
4
Q
Infections could be:
A
- Endogenous - arise from within the body e.g. bacteria
- Exogenous - superficial layers of the skin
- Subclinical - asymptomatic
- Clinical - disease
- Caused by flora, colonising organisms, or exogenous organisms
5
Q
Types of skin infections:
A
- Cellulitis - affects dermis & subcutaneous tissues (deeper layers)
- Erysipelas - superficial layers of the skin
- Impetigo - school sores
- Shingles / Chicken pox - caused by the same virus
- Necrotising faciiitis
- Carbuncles (boils) - caused by S. aureus
- Lymphangitis (associated with cellulitis)
6
Q
Cellulitis: How does bacteria cause illness?
A
- Bacteria colonise skin
- Bacterial toxins (cytolysins) damage epithelial cells
- Damaged epithelial cells release cytokines (e.g. IL-1, TNF-a, IL-8 which contributes to neutrophil chemotaxis)
+ Cytokines are produced by injured & healthy cells (via stimulation of TLRs)
+ IL-1 & TNF-a instruct capillary endothelial cells to express cellular adhesion molecules (e.g. selectins, CAMs) - Skin macrophages & dendritic cells follow chemical gradient to the site of infection - also release cytokines
- Selectins interact with carbohydrates on neutrophils causing them to slow, roll & tether to epithelium - diapedesis
- Tethered neutrophils are pulled between the epithelium (vie PECAM interactions) & migrate to the site of infection - chemotaxis
- PAMPs (e.g. peptidoglycan lipotechoic acid) bind to PRRs (e.g. toll-like receptors) which activate innate immunity
7
Q
Complement immune response
A
- Lectin pathway: Bacterial carbohydrates binds to proteins
- Alternative pathways: Complement spontaneously starts to form on cell surfaces
- Classical pathways: Antibody, immunoglobin binds to bacterial antigen
- Once triggered a number of proteins combine to for C3 convertase which cleaves C3 into C3a & C3b
+ C3b is an opsonin - binds to bacteria & enhances recognition & phagocytosis - Some C3b binds back to the C3 convertase to form C5 convertase which cleaves C4 in C5a & C5b
+ C5b binds with C6 to C9 to form the membrane attach complex (MAC) which lyses bacteria (gram negative) - C3a & C5a are anaphylatoxins - increase vascular permeability
+ C5a is also a chemotactic protein
8
Q
End result of bacterial infections (Cellulitis)
A
- Increased vascular permeability in the skin leads to erytherma
- Changes to larger vessels & lymphatic vessels leads to swelling
- Purulent materials contain neutrophils & other phagocytes, dead cells, viable bacteria, dead bacteria, cell debris & extracellular protein
- Cytokines, cellular debris & bacterial degradation products stimulate nerves to cause pain
9
Q
Causes of cellulitis
A
- Streptococcus pyrogenes
- Staphylococcus aureus
- Other bacteria
10
Q
Causes of boils/furuncles:
A
- S. aureus
11
Q
Causes of other skin infections:
A
- Fungi
- Viruses
12
Q
Streptococcus pyrogenes:
A
- Gram positive cocci
- Colonises 10-15% of oropharynx
- Also causes: Pharyngitis, Skin & soft tissue infections
- Bone & joint infections
- Rheumatic fever
13
Q
How does S. pyrogenes avoid the immune system & cause disease”
A
- Various toxins (streptolysins) damage cells such as neutrophils & platelets
- DNAses digest DNA to avoid being trapped in neutrophil extracellular traps
- Streptokinase activates plasminogen into plasmin which digests fibrin
- Adhesins which bind to host tissues (MSCRAMMs = microbial surface components recognising adhesive matrix molecules)
- Hyaluronic acid capsule prevents opsonisation & phagocytosis
- C5a peptidase degrades C5a reducing chemotaxis
- M proteins (another MSCRAMM) binds factor H, which degrades complement
+ M proteins also interfere with C3 binding to C3b receptor on phagocyte cell
+ There are different types of M proteins & often a particular M protein is associated with a particular disease
14
Q
Diagnosis of bacterial illness (cellulitis)
A
- Clinical (look at skin) + Blood tests looking for antibodies/cytokines
- Lab swabs of purulent material
- If admitted to hospital, blood cultures should also be taken
+ Very sick individuals should be tested for sepsis (e.g renal failure)
15
Q
Treatments for cellulitis
A
- Antimicrobial drugs that are primarily directed at S. pyrogenes & S. aureus
- Analgesia
- Lifestyle changes such as supportive care (maintain “normla” physiology), rest & elevation