Session 3 Flashcards
(38 cards)
What is sepsis?
Sepsis describes a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. It is usually caused by bacterial infection.
What are the causative agents for sepsis?
Causative agents depend on the syndrome, host and clinical context. Gram-negative infections account for an increasingly large proportion of cases, particularly of healthcare-associated infections
What are the clinical features of sepsis?
Common presenting syndromes include pneumonia, intraabdominal and urinary sepsis, and skin and soft tissue infections. You will therefore expect to see all the common features of an infection, with the addition of features of a body organ that is not functioning and failing to work properly. Commonly more than one body system is affected. This can include: • Cardiac • Respiratory • Central Nervous System • Liver • Gastro-intestinal tract
What investigations would e done when looking at sepsis?
Investigations aim to confirm the presence, source and severity of infections and alternative diagnoses. Where possible, it is important to obtain samples for microbiology before administering antibiotics to maximize culture sensitivity. Except in exceptional circumstances, at least one set of blood cultures should be obtained. The timing of other cultures (e.g. urine, cerebrospinal fluid, and repeat blood cultures) depends on the clinical presentation, illness severity and likely delay in obtaining a sample; in general, however, antibiotics should not be delayed in true sepsis.
How is sepsis managed?
Management The key principles of management are prompt recognition, early appropriate antimicrobial therapy and supportive treatment Elements of the initial management of sepsis are incorporated into the Sepsis Six bundle of care (this will be tested and suggest you write it out). Rapid clinical assessment is indicated for all patients with suspected sepsis. Rapid delivery of a bundle of care comprising elements of the Sepsis Six has been associated with reduced mortality in sepsis
How is sepsis treated?
Antimicrobial therapy should be administered as rapidly as possible in sepsis, and within 1 hour, as early appropriate antibiotics are associated with improved survival. The choice of initial empirical antibiotic therapy depends on the presenting clinical syndrome (including likely focus of infection, neutropenia, etc.) and should follow local guidelines based on the most likely pathogens and susceptibility profiles. Supportive treatment includes oxygen to treat hypoxia and ensure good tissue oxygenation, and intravenous fluids to optimize tissue perfusion. Vasopressors and inotropes (drugs to improve cardiac output and maintain blood pressure) may be required in septic shock, mechanical ventilation for severe pneumonia or acute respiratory distress syndrome, and renal replacement therapy for acute kidney injury. Patients who present in septic shock or who fail to respond to initial therapy should be referred early to intensive care for further organ support.
How does the immune system cause damage in sepsis?
In ‘sepsis’ the normal immune response which is designed to recognise and eliminate the microbe becomes greatly exaggerated (or dysregulated) so that the consequence for the patient is damage inflicted by their own immune response. That response is not only exaggerated but also perpetuates itself so that the patient’s clinical condition deteriorates and may be fatal.
Immune-system activation:
• The innate immune system is activated by bacterial cell wall products, such as lipopolysaccharide (endotoxin) binding to host receptors, including Toll-like receptors (TLRs). These are widely found on monocytes and macrophages, and some types are found on endothelial cells. These have specificity for different bacterial, fungal, or viral products.
• Activation of the innate immune system results in a complex series of cellular and humoural responses, each with amplification steps:
* Pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukins 1 and 6 are released, which in turn activate immune cells.
* The complement system is activated, and mediates activation of leukocytes, attracting them to the site of infection where they can directly attack the organism.
What is the endothelium and coagulation system in sepsis?
- The vascular endothelium plays a major role in the host’s defence to an invading organism, but also in the development of sepsis. Activated endothelium not only allows the adhesion and migration of stimulated immune cells, but becomes porous to large molecules such as proteins, resulting in the tissue oedema.
- Alterations in the coagulation systems include an increase in procoagulant factors, such as plasminogen activator inhibitor type I and tissue factor, and reduced circulating levels of natural anticoagulants. Clinically this is seen as clotting in small vessels but often a tendency to bleeding at other sites. This is the typical picture seen in sepsis caused by Neisseria meningitides
How does sepsis cause inflammation and organ dysfunction?
Inflammation and organ dysfunction:
• Through vasodilatation (causing reduced systemic vascular resistance) and increased capillary permeability (causing extravasation of plasma), sepsis results in relative and absolute reductions in circulating volume.
• A number of factors combine to produce multiple organ dysfunctions. Relative and absolute hypovolaemia are compounded by reduced left ventricular contractility to produce hypotension. Initially, through an increased heart rate, cardiac output increases to compensate and maintain perfusion pressures, but as this compensatory mechanism becomes exhausted, hypo perfusion, and shock may result.
• Impaired tissue oxygen delivery is exacerbated by pericapillary oedema. This means that oxygen has to diffuse a greater distance to reach target cells. There is a reduction of capillary diameter due to mural oedema and the pro-coagulant state results in capillary microthrombus formation.
What is septic shock?
Septic shock occurs when severe sepsis leads to circulatory failure and metabolic abnormalities, defined as persisting hypotension requiring active medical treatment and biochemical evidence of disturbed metabolism (raised lactate).
What happens in local infection.
Acute inflammation: Rubor - Redness Tumor - Swelling Calor - Heat Dolor - Pain
What are the effects of sepsis on organ symptoms?
Airways - No specific effect unless infection arises from throat or neck. However, decreased consciousness may be at risk of airway problems.
Breathing - Raised respiratory rate (tachypnoea). Fluids and proteins leaking into interstitial tissues lead to lung oedema and decreased lung compliance.
Circulation Hypovolaemia due to vasodilatation and capillary leakage leading to hypotension.
Blood Pressure = cardiac output x systemic vascular resistance
Tachycardia
End organ damage
Disability - Reduced blood flow to brain. May present as confusion, drowsiness, slurred speech, agitation, anxiety or decreased level of consciousness.
Exposure - High temperature due to hypothalamic response to infection. Beware hypothermia (t < 36°C) especially in elderly.
What are the key identifiable symptoms to be aware of the signify sepsis?
Slurred speech or confusion Extreme shivering or muscle pain Passing no urine (in a day) Severe breathlessness It feels like you're going to die Skin mottled or discoloured
Who is especially at risk of sepsis?
- Very young (< 1 year old).
- Elderly (>75 years) or very frail.
- Pregnant, post partum (within last 6 weeks).
- Patients with impaired immune system due to illness or drugs.
What is the national early warning score?
• Scores allocated to six difference physiological measurements:
- respiration rate
- oxygen saturation
- systolic blood pressure
- pulse rate
- level of consciousness or new confusion*
- temperature.
Score of 5 or more, think sepsis however some will constantly flag high e.g higher breathing rate for patients with COPD
What is red flag sepsis?
Set of criteria indicating a high risk of deterioration from sepsis. Only one of the red flag criteria needs to be present.
- AVPU = V,P or U (if changed from normal)
- Acute confusion
- Respiratory rate above or equal to 25/min
- Oxygen saturation needs to be above 92% (88% in patients with COPD)
- Heart rate above 130bpm
- Systolic BP less that or equal to 90mmHG or a from of more than 40 compared to normal
- Not passed urine in the last 18 hours or less then 0.5ml/kg/hr
- Non-blanching rash, mottled/ashen/cyanotic
- Recent chemotherapy (last 6 weeks)
How is sepsis managed?
This will be in the exam
Sepsis 6 is a set of six tasks (known as a care bundle) that has been shown to greatly increase the patient’s chance of survival if delivered within the first hour following recognition of sepsis.
- Give oxygen
- Take blood culture
- Give IV antibiotics
- Give fluids
- Take Hb and lactate
- Monitor urine output
What supportive and specific investigations might you do for a patient with sepsis?
Supportive investigations: Full blood count, Urea and Electrolytes Blood sugar Liver Function Tests C-Reactive protein (CRP) Coagulation (clotting) studies Blood gases
Specific investigations: Cerebrospinal Fluid
Throat swab
EDTA bottle for PCR
How might we look at cerebrospinal fluid?
- Obtained by lumbar puncture
- Urgent transport of CSF to laboratory
- Glucose and protein estimation in biochemistry, microscopy and culture in microbiology
- Appearance –turbidity and colour
- Microscopy WBCs, RBCs
- Gram stain
- Referral for PCR
What do naïve T cells require to start attacking pathogens?
Antigen presenting cells must be present in order to activate T cells.
What are the features of antigen presenting cells?
• Strategic location (B and T cell interaction)
o Mucosa associated lymphoid tissue (MALT)
-Skin (SALT)
-Mucous membranes (GALT(gut), NALT(nasal), BALT(bronchial), GUALT (genitourinary)
-Tonsils or Peyer’s patches
o Lymphoid organs (Lymph nodes, spleen)
o Blood circulation (plasmacytoid and myeloid DCs)
• Pathogen capture o Phagocytosis (whole microbe) o Macropinocytosis(soluble particles e.g. toxins from bacteria)
• Diversity in pathogen sensors (PRRs - pathogen recognition receptors)
o Extracellular pathogens (bacteria)
o Intracellular pathogens (viruses)
Give examples of toll like receptors and what they detect.
Many toll like receptors share properties with each other so can detect multiple types of organism.
Extracellular detect bacteria fungi and protozoa. e.g. :
Gram positive bacteria such as : Staphylococcus aureus, Streptococcus pneumoniae can be detected by TLR1 TLR2 and TLR6.
gram negative bacteria such as Neisseria meningitidis, E. Coli can be detected by TLR 4 and TLR 5.
Intracellular toll like receptors generally detect viruses as the viruses normally bypass the plasma membrane. e.g.:
dsDNA viruses such as adenovirus can be detected by TLR9 and single stranded viruses such as norovirus can be detected by TLR8
What are the different types of antigen presenting cell, what is their location and what do they present to?
Dendritic cells are located in the lymph nodes, mucous membranes and blood and present to naïve T cells
Langerhans cells are located in the skin and present to naïve T cells.
Macrophages are located in various tissues and present to Effector T cells.
B cells (BCR) are located in lymphoid tissues and present to both effector T cells and naïve T cells.
What does processing a microbe mean?
Degrading in such a way that it can be recognised by antigen presenting cells.
