Infection Flashcards
How does HIV spread?
Sexual transmission Injection drug misuse Blood products Vertical transmission Organ transplant
What does HIV do in terms of immunology?
Infects and destroys cells of the immune system especially the T-helper cells that are CD4+.
What does the CD4 count tell us about the illness?
The lower the CD4 count - the greater the severity of the illness.
AIDS occurs at CD4 <200
How is HIV classified?
Clinical staging:
Stage 1 - asymptomatic.
Stage 2 - Weight loss <10% body weight. Minor mucocutaneous manifestations. Recurrent upper respiratory tract infections.
Stage 3 - Weight loss >10% body weight. Unexplained chronic diarrhoea > 1 month. Unexplained prolonged fever >1 month. Oral thrush. Severe bacterial infections. (bedridden)
Stage 4 - HIV wasting syndrome. Toxoplasmosis of the brain. Herpes simplex virus infection. Candidasis of the oesophagus, trachea. HIV encephalopathy.
Bedridden <50% of day during last month.
What is the natural history time line of HIV?
Acute infection Asymptomatic HIV related illnesses AIDS defining illness Death
How does primary HIV present?
Abrupt onset 2-4 weeks post exposure. Symptoms generally non-specific: Flu-like illness Fever Malaise and lethargy Pharyngitis Lymphadenopathy Toxic exanthema
What is Pneumocystis jiroveci pneumonia?
Commonest late stage (AIDS) infection.
CD4 cell count usually <200.
Classical history of dry cough and increasing breathlessness over several weeks.
What investigations are done for Pneumocystis jiroveci pneumonia?
Chest X-ray
Induced sputum or broncoscopy for PCR.
How is PJP treated?
Cotrimoxazole
Pentamidine
Prophylaxis until CD4 > 200.
How is HIV treated?
Combination Antiretroviral therapy (cART) at least 3 drugs from at least 2 groups.
- side effects can be significant.
When should treatment begin?
All patients at diagnosis regardless of CD4 and viral load.
Any pregnant woman - start before 3rd trimester.
How long is treatment needed for HIV?
Life long. Treatment may need to be changed from time to time but will always need to be taking some form of antiviral medication.
Why do treatments for HIV fail?
Poor adherence leads to viral mutation and resistance.
What type of antiviral drugs are there?
Nucleoside reverse transcriptase inhibitors - marrow toxicity, neuropathy, lipodystrophy.
Non-nucleoside reverse transcriptase inhibitors - skin rashes, hypersensitivity, drug interactions.
Protease inhibitors - drug interactions, diarrhoea, hyperlipidemia.
Integrase inhibitors - disturbed sleep, rashes.
What are the challenges of HIV care?
Osteoporosis Cognitive impairment Malignancy Renal disease Ischaemic heart disease Diabetes mellitus
How can HIV be prevented?
Behaviour change and condoms. Circumcision Treatment vs prevention - VL undetectable = untrasmissable. Pre-exposure prophylaxis (PrEP) Post-exposure prophylaxis for sexual exposure (PEPSE)
What is the definition of Sepsis?
Life-threatening organ dysfunction caused by dysregulated host response to infection.
What are the stages of sepsis?
SIRS - temp >38, HR > 90, WBCs >12,000.
Sepsis = SIRS and infection
Severe Sepsis = Sepsis and end organ damage.
Septic Shock = Severe sepsis and hypotension
What is Septic shock?
Identified with clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP>65mmHg and having serum lactate of >2.
Hospital mortality of 40%.
What is qSOFA?
Patients with suspected infection who are likely to have prolonged ICU stay or die in the hospital can be promptly identified using this criteria.
Score of >2 suggest a greater risk of poor outcome.
What is the pathophysiology behind sepsis?
uncontrolled inflammatory response.
Patients have features consistent with immunosuppression.
- loss of delayed hypersensitivity, inability to clear infection.
Probable change of the sepsis syndrome over time.
Initially increase in inflammatory mediators.
Later, shift toward an anti-inflammatory immunosuppressive phase.
What is the first phase in the pathogenesis of sepsis?
Release of bacterial toxins:
May or may not be neutralised and cleared by existing immune system.
Commonly released toxins = gram negative - LPS.
Gram positive - MAMP
Superantigens - Staphloccocal toxic shock syndrome toxin.
What is the 2nd phase in the pathogenesis of sepsis?
Release of mediators in response to infection:
Effects of infections due to endotoxin release.
Effects of infections due to exotoxin release.
Mediator role of sepsis.
What are the mediator role in sepsis? (Th1 vs Th2)
Pro-inflammatory mediators - causes inflammatory response that characterises sepsis.
Compensatory anti-inflammatory reaction - can cause immunoparalysis.
What is phase 3 in pathogenesis of sepsis?
Effects of specific excessive mediators:
Pro-inflammatory mediators:
- promote endothelial cell
- release of arachidonic acid metabolites.
- Complement activation.
- Vasodilatation of blood vessels by NO.
- Increase coagulation by release of tissue factors and membrane coagulants.
- Cause hyperthermia.
Anti-inflammatory mediators:
- Inhibit TNF alpha
- Augment acute phase reaction.
- inhibit activation of coagulation system.
- Provide negative feedback mechanisms to pro-inflammatory mediators.
What happens when the pro-inflammatory response is greater than compensatory anti-inflammatory response?
Septic Shock with multi-organ failure and death.
What happens when the compensatory anti-inflammatory response is greater than pro-inflammatory?
Immunoparalysis with uncontrolled infection and multiorgan failure.
What does the clinical features of sepsis depend on?
Number of factors:
Host.
Organsim.
Environment.
What are the general features of sepsis?
Fever >38 - presenting as chills, rigors, flushes, cold sweats, night sweats.
Hypothermia <36 - especially in the elderly and very young children.
Tachycardia >90 per min
Tachypnoea > 20/min
Altered mental status - especially elderly.
Hyperglycaemia > 8 in absence of diabetes.
What are the inflammatory variable in sepsis?
Leucocytosis
Leucopenia
High CRP
High Prolactin
What are the organ dysfunction variable in sepsis?
Arterial hypoxaemia Oliguria Creatinine increase compared to baseline. Coagulation abnormalities. ileus (intestinal obstruct) Thrombocytopenia (low platelet) Hyperbilirubinaemia
Tissue perfusion variables in sepsis
High lactate
Skin mottling and reduced capillary perfusion.
Effect of host on sepsis presentation
Age
Co-morbitdities (COPD, DM)
Immunosuppression
Previous surgery
Effect of organism on presentation of sepsis
Gram positive vs Gram negative.
Virulence factors
Bioburden.
What is the sepsis 6?
Oxygen Blood cultures Antibiotics Fluid challenge Lactate Urine output
Take 3: Give 3
Take: Blood cultures
Blood lactate
Measure urine output
Give: oxygen aim for 94-98%
IV antibiotics
IV fluid challenge
Why take blood cultures, lactate and urine output?
BC - Make microbiological diagnosis (30-50% positive)
- if spike in temp, take 2 sets.
Lactate - marker of generalised hypoperfusion / severe sepsis/ poorer prognosis.
Type A - hypoperfusion. Type B - mitochondrial toxins.
Low urine output - marker of renal dysfunction.
What antibiotics are chosen in sepsis?
Based on working diagnosis from history and examination.
Follow local antibiotic guidelines.
Consider allergy, previous MRSA, ESBL, and toxicity.
What is given in IV fluids for sepsis?
30ml/kg fluid challenge
2.1L 70kg patient.
When is HDU referral considered in sepsis?
Low BP responsive to fluids Lactate >2 despite fluid resuscitation. Elevated creatinine Oliguria Liver dysfunction Bilateral infiltrates, hypoxaemia.
When is ITU considered for sepsis?
Septic shock
Multi-organ failure
Requires sedation, intubation and ventilation.
