Infectious disease emergency Flashcards
What is the definition of sepsis?
Sepsis is clinical evidence of infection together with 2 or more of the following quick Sequential [Sepsis-related] Organ Failure Assessment score (qSOFA) criteria: altered mentation (Glasgow Coma Scale <15), respiratory rate ≥22/min, and systolic BP ≤100 mm Hg.
What are the components of the quick Sequential [Sepsis-related] Organ Failure Assessment score (qSOFA)?
The qSOFA score includes:
1. Altered mentation (Glasgow Coma Scale <15)
2. Respiratory rate ≥22/min
3. Systolic BP ≤100 mm Hg.
How is septic shock defined?
Septic shock is sepsis with hypotension (systolic BP <90 mm Hg or a greater than 40 mm Hg fall in systolic BP) persisting despite adequate fluid resuscitation.
Effect of sepsis on the liver
Liver injury
- Impaired detoxification
-Impaired coagulation system
*Bleeding and DIC
- Altered metabolic response
- Hyper/ hypo glycemia
-Bilirubinemia
* Cholestasis
* Jaundice
Effect of sepsis on the intestines
Compromisation of intestinal barrier
- Release of bacteria into the system
* Peritonitis
Effect on sepsis on the lungs
Acute respiratory distress syndrome
-Leaky capillaries
*Compromised oxygen delivery
-Access route for secondary infection
Effect of sepsis on the thyroid
- Apoptosis
-Impaired T lymphopoiesis
Effect of sepsis on the lymph vessels
- Abcess formation
-Compromised local immune cell function
Effect of sepsis on the brain
Encephalopathy
- Coagulopathy
- Hypoxic ischemic brain damage
-Blood brain barrier dysfunction
-Decreased neurotransmitter release
* Delirium
Effect of sepsis on the heart
Heart failure
- Reduced oxygen in system causes heart to pump faster (>90 bpm)
- Abnormal O2 delivery
- Hypotension
-Defective contractibility
* Decreased cardiac output
Effect of sepsis on the spleen
Splenic pathology
- Splenomegaly
-Atrophy of lymphoid follicles
* Immune cell apoptosis
* Immunosupresion
Effect of sepsis on the kidneys
Renal failure
-Ischemia of tissue
Effect of sepsis on the bones
Bone marrow suppression
- Myelosupression/ lymphopaenia
- Apoptosis of WBVs
What is a proinflammatory response?
A proinflammatory response is the body’s immediate reaction to harmful stimuli, such as pathogens (bacteria, viruses), injury, or toxins. This response involves the activation of the immune system to fight off the perceived threat.
What is an antiinflammatory response?
An antiinflammatory response is the body’s mechanism to regulate and suppress the inflammatory process to prevent excessive tissue damage and to promote healing.
Why is the balance between proinflammatory and antiinflammatory responses important?
The balance between proinflammatory and antiinflammatory responses is crucial for maintaining health. An appropriate proinflammatory response is necessary to fight off infections and heal injuries, but it must be regulated by antiinflammatory mechanisms to prevent excessive tissue damage and chronic inflammation. Conversely, an excessive antiinflammatory response can lead to immunosuppression and increased vulnerability to infections. Maintaining this balance is essential for the body’s immune homeostasis and overall health
Proinflammatory response
- Host and pathogen interaction
- Pattern recognition receptors
-Signaling cascade - Leukocyte activation and infiltration
- Excessive cytokine release
- Complement activation
-Coagulation cascade activation
Anti-inflammatory response
- Impaired immune cell function
- Cell apoptosis and immune regulation
What do Pattern Recognition Receptors (PRRs) recognize?
PRRs recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
What happens after PRRs recognize PAMPs and DAMPs?
A cascade of intracellular signaling events occurs, leading to cytokine synthesis
What results from excessive cytokine release?
An increase in circulating immune cells.
What role does the complement system play?
It marks pathogens for destruction.
What does the coagulation cascade produce?
Coagulation products.
How are macrophages affected in the antiinflammatory response?
Impaired phagocytosis.
What defects occur in neutrophils?
Maturation defects.
How are NK cells affected?
Defective cytotoxic function.
What happens to T, B, and dendritic cells during the antiinflammatory response?
Programmed cell death (apoptosis).
What leads to immunosuppression during the antiinflammatory response?
Expansion of regulatory T cells.
What does an excessive inflammatory response lead to?
Tissue damage.
What happens during the immunosuppressive state in sepsis?
Increased vulnerability to secondary infections.
What initiates the coagulation cascade in the process of increased coagulation?
Monocytes release tissue factor, which initiates the coagulation cascade.
How do neutrophils contribute to the formation of thrombi (clots)?
Neutrophils form neutrophil extracellular traps (NETs) with trapped platelets, contributing to the formation of thrombi.
What are the main factors reduced in decreased anticoagulation?
Reduction in tissue factor pathway inhibitor and antithrombin levels.
What happens to thrombomodulin (TM) and endothelial protein C receptor (EPCR) in decreased anticoagulation?
Trombomodulin (TM) and endothelial protein C receptor (EPCR) are decreased, leading to reduced activation of protein C.
How does decreased activated protein C affect fibrinolysis?
Decreased levels of activated protein C result in reduced fibrinolysis, enhanced by an increase in plasminogen activator inhibitor-1 (PAI-1).
What effect does the formation of thrombi in the microcirculation have on tissue perfusion?
Formation of thrombi in the microcirculation leads to tissue hypoperfusion.
How does tissue hypoperfusion affect tissue oxygenation?
Tissue hypoperfusion results in decreased tissue oxygenation, contributing to mitochondrial dysfunction and release of mitochondrial contents, further exacerbating the condition.
What role do endothelial cells and PAR1 play in the loss of barrier function?
Endothelial cells express PAR1 (protease-activated receptor 1), activated by thrombin and protein C.
What happens to VE-cadherin and tight junctions in the loss of barrier function?
Decreased VE-cadherin and tight junctions cause increased capillary leak and interstitial edema.
What are the consequences of increased capillary leak and interstitial edema?
This leads to cell shrinkage, cell death, and further loss of barrier function.
What systemic changes occur due to the loss of barrier function?
Vasodilation and decreased blood pressure occur, reducing red cell deformability
How do these systemic changes affect tissue oxygenation and organ function?
These changes lead to decreased tissue oxygenation, resulting in organ failure
What are the key disturbances highlighted in the diagram that lead to microcirculatory problems and organ failure?
Disturbances in coagulation and anticoagulation, combined with endothelial dysfunction, lead to microcirculatory problems, tissue hypoperfusion, decreased tissue oxygenation, and ultimately organ failure.
What condition is characterized by this pathophysiology?
This pathophysiology is characteristic of conditions like sepsis, where a hyperinflammatory state results in significant vascular and tissue damage.
What is the first step in managing sepsis according to key management principles?
Start appropriate resuscitation and general support measures urgently.
What are examples of resuscitation and general support measures in sepsis management?
Examples include administering oxygen and maintaining fluid balance with isotonic crystalloids.
When are inotropic agents used in the management of sepsis?
Inotropic agents are used for patients experiencing shock.
What inotropic agent is typically used for shock in sepsis management?
Adrenaline (epinephrine) infusions are typically used
How should empiric antimicrobials be selected in sepsis management?
Select empiric antimicrobials that are appropriate for the likely infecting organism/s.
How should empiric antimicrobials be administered?
Empiric antimicrobials should always be given intravenously and include a loading dose.
When should empiric antimicrobials be given in sepsis management?
Empiric antimicrobials should be given as soon as possible.
Reason for starting antibiotics soon
reduces the probability of experiencing hypotension
Why is the absorption of drugs from the gastrointestinal tract (GIT), subcutaneous (s/c), or intramuscular (IM) routes poor in sepsis patients?
The absorption of drugs from these routes is poor due to altered haemodynamics.
How must antimicrobials be administered in sepsis management?
Antimicrobials must be given intravenously.
What is the effect of an increased cardiac index during sepsis?
An increased cardiac index leads to increased clearance of drugs.
What occurs during sepsis to the organs
- Increased cardiac index
- Leaky capillaries and/ or altered protein binding
- End organ dysfunction (e.g renal or hepatic)
What is the result of increased drug clearance on serum concentrations of medications?
It results in low serum concentrations of medications due to faster elimination from the body.
How do leaky capillaries and altered protein binding affect the volume of distribution during sepsis?
They cause an increased volume of distribution.
What is the result of an increased volume of distribution on serum concentrations of medications?
It results in low serum concentrations of medications as the drug is dispersed in a larger volume within the body.
What effect does end-organ dysfunction (e.g., renal or hepatic) have on drug clearance during sepsis?
End-organ dysfunction results in decreased clearance of drugs.
What is the result of decreased drug clearance on serum concentrations of medications?
It results in high serum concentrations of medications due to slower elimination from the body.
What can cause low serum concentrations of medications during sepsis?
Low serum concentrations can occur due to increased clearance and increased volume of distribution.
What can cause high serum concentrations of medications during sepsis?
High serum concentrations can occur due to decreased clearance.
Why is it important to understand the pharmacokinetic effects of sepsis on drug dosing?
Understanding these effects is crucial for adjusting drug dosing to achieve therapeutic efficacy and avoid toxicity.
What is the definition of the volume of distribution (Vd)?
The volume into which a drug appears to distribute with a concentration equal to that of plasma.
How is Vd calculated?
Vd = amount of drug in the body / plasma concentration.
How does the solubility of a drug affect its volume of distribution (Vd)?
Water-soluble drugs have a lower Vd, while lipid-soluble drugs have a higher Vd.
What does it mean if a drug has a very high volume of distribution (Vd)?
A very high Vd means much higher concentrations of the drug in tissue than in blood.
Can the volume of distribution (Vd) exceed any physical volume in the body?
Yes, Vd can vastly exceed any physical volume.
Why is the volume of distribution (Vd) important in drug dosing?
Vd determines the loading dose (LD) of a drug.
How is the loading dose (LD) of a drug calculated?
D = Vd * desired plasma concentration.
Why is it important to give a loading dose of colistin in septic patients?
To quickly achieve therapeutic levels of colistin in the blood, which is crucial for effective treatment in severe infections.
What is the effect of a higher loading dose (12 MU) of colistin?
It results in faster and higher therapeutic levels of colistin in the blood, beneficial for rapidly achieving effective drug concentrations.
What is the effect of a lower loading dose (9 MU) of colistin?
It achieves therapeutic levels more slowly and maintains lower concentrations compared to the higher loading dose.
What is the effect of not giving a loading dose of colistin?
It significantly delays the achievement of therapeutic levels, potentially delaying effective treatment.
What does the choice of loading dose of colistin impact?
It impacts both the speed and level of colistin concentration achieved in the body, influencing the overall effectiveness of the treatment.
What clinical criteria are used in the CRB-65 score for assessing the severity of severe community-acquired pneumonia (CAP)?
The criteria are:
-Confusion
-Urea elevated (>7 mmol/L)
-Respiratory rate >30/min
-Blood pressure low (systolic <90 or diastolic ≤60 mmHg)
-Age ≥65
How is the CRB-65 score calculated?
Score 1 point for each criterion.
Can the CRB-65 score be used without the urea criterion?
Yes, it can be used without the urea criterion as the CRB-65 score.
What does a CRB-65 score of 0 or 1 indicate for treatment?
May be suitable for outpatient therapy. Mortality is 1.2%.
What does a CRB-65 score of 2 indicate for treatment?
Hospitalize. Mortality is 8.2%
What does a CRB-65 score of 3 or more indicate for treatment?
Treat as severe CAP. Mortality is 31%.
Why is it important to understand the different categories of pathogens in community-acquired pneumonia (CAP)?
Understanding the different categories and their overlaps is crucial for diagnosing and treating respiratory infections effectively.
What are the primary categories of pathogens that cause community-acquired pneumonia (CAP)?
The primary categories are:
Typical Bacteria
Atypical Bacteria
Viruses
Why might treatments for conventional bacterial infections not be effective for atypical bacteria or viruses?
Atypical bacteria and viruses have different biological characteristics, making treatments effective for typical bacteria ineffective.
Why is accurate identification of the pathogen involved in CAP crucial?
Accurate identification is essential for selecting appropriate therapy, as treatments vary significantly between different pathogens.
How should antimicrobials be initially administered in severe community-acquired pneumonia (CAP)?
Antimicrobials must be commenced intravenously (can switch to oral once improving)
What antimicrobial regimen is recommended for covering Gram-positive and Gram-negative conventional bacteria in severe CAP?
A broad-spectrum β-lactam is recommended.
What additional antimicrobial is recommended to cover atypical bacteria in severe CAP?
A macrolide is recommended
When should oxygen be administered to a patient with severe CAP?
Oxygen should be given if saturation is less than 94%.
What other supportive measures should be considered in managing severe CAP?
Other resuscitative measures should be considered as needed
Features of severe malaria
- Decreased level of consciousness
- Seizures
- Prostration (inability to drink or sit unaided)
- Shock
- Acidosis
- Severe anemia (Hb < 7g/ dL)
- Visible jaundice
- Renal impairment
- Parasitaemia >=5% of red cells
- Hypoglycemia
- Respiratory distress
What is nearly always the cause of severe malaria?
Plasmodium falciparum infection.
Who are at higher risk of severe malaria in endemic areas with year-round transmission?
The higher-risk groups include:
-Young children
-Pregnant individuals
-HIV-positive individuals
-All people from areas without malaria or with seasonal malaria
What should you do if you are uncertain about the criteria for severe malaria or have a concerned patient?
Treat as severe malaria.
What is the drug of choice for treating severe malaria?
Artesunate is the drug of choice.
What should be considered regarding fluid therapy in severe malaria?
Be cautious with fluids, as over-hydration can cause respiratory failure.
What is the strongest predictor of outcome in bacterial meningitis?
The level of consciousness when treatment is started.
How can consciousness levels change in bacterial meningitis?
Consciousness can decrease rapidly.
Prognosis and time of starting antibiotics
if you start antibiotics prognosis is high and low mortality rate
What is the urgent treatment step for bacterial meningitis in primary care?
Give broad-spectrum antibiotics intravenously.
Are adjunctive steroids recommended for bacterial meningitis management in South Africa?
No, adjunctive steroids are not recommended in South Africa.
How do the recommendations for adjunctive steroids differ between high-income and low-middle income countries?
Adjunctive steroids are recommended in high-income countries but were not effective in trials in low-middle income countries.
