Describe the Sepsis Six Bundle with regard to Adaptive Immunity
Give 3, take 3:
Give:
- (IV) Antibiotics
- Fluids
- Oxygen (if appropriate)
Take:
- Cultures (blood)
- Urine (monitor urine output)
- Lactate and Hb
Within the first hour, following the recognition of sepsis
Describe the main microbiological features of Streptococcus pneumoniae
- Gram positive cocci
- Facultative anaerobe
Describe the relevant anatomy and physiology linked to pneumonia
Anatomy:
Airways of lungs:
- Trachea
- Bronchi
- Smaller bronchioles
- Alveoli (where gas exchange happens)
Each lung divided into lobes - right lung =3 left lung = 2
- Air enters into the lung and reaches the alveoli. In the alveoli OXYGEN moves from the air into capillaries where it is bound to haemoglobin.
- CO2 moves from capillary to the alveoli to be expelled from lungs
- Pneumonia is infection of alveoli and tissue of the lungs
- Alveoli may become inflamed and fill with fluid or pus
- Causes cough with phlegm or pus, fever, chills, difficulty breathing
- Since the alveoli are the main gas exchange surface for replenishing the blood oxygen levels, infection and damage to the alveoli in viral and/or bacterial pneumonias can be severe and life-threatening.
Identify the specific and supportive tests for sepsis
Specific: (3)
- Cerebral spinal fluid - test for meningitis using microscopy and PCR
- Throat swab
- EDTA bottle for PCR
Supportive: (7)
- Full blood count
- Urea and electrolytes
- Blood sugar
- CRP
- Liver function tests
- Coagulation studies (to assess liver function)
- Blood gases (look at the oxygen sat)
Which individuals are at an increased 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 (diabetes, chronic
kidney failure, HIV etc.) or drugs (steroids, immunosuppressant etc.)
Understand the principles of supportive and specific treatment for acute sepsis
Describe sepsis prevention
Specific - Directly treat the infection causing septic shock
- Antibiotics which crosses blood brain barrier - Ceftriaxone (usually first line)
Supportive - Treat only symptoms of sepsis
- Sepsis 6 bundle
Prevention:
- Vaccination against meningitis
- Prophylaxis for close contacts
Describe red flag sepsis and NEWS
- ‘Red Flag Sepsis’ is not a formal diagnosis! It identifies septic patients that are at high risk of deterioration/ end organ dysfunction.
- Sepsis is diagnosed via nursing baseline observations (NEWS)! :
- Respiration rate
- Oxygen saturation
- Systolic blood pressure
- Pulse rate
- Level of consciousness or new confusion*
- Temperature
Understand the features of acute sepsis
Sepsis - life threatening organ dysfunction due to dysregulated host response to infection
Capillary leakage - allow inflammatory response and causes tumor(swelling)
Amplification of immune system- increased cell signal activity (can lead to dolor(pain))
Vasodilation - increases blood cells in area - rubor and calor
- Increased heart rate
- Increased respiratory rate
- Decreased urine output
- Decreased blood pressure
- As a result of reduced blood perfusion to the brain, patients can present with:
- Confusion
- Drowsiness
- Slurred speech
- Agitation
- Anxiety
- Reduced level of consciousness.
Describe the role of the innate immune system and microbiota relating to infections of the lower respiratory tract
Physical barriers - Mucocillary escalator/Mucosal membrane, bronchial cilia
Physiological barriers - coughing/cough reflex and sneezing
Chemical barriers - antimicrobial molecules ie immunoglobulin A (IgA)
Biological barriers - normal flora
Describe and identify Adenovirus(double stranded DNA)as a cause of upper respiratory tract infections with regard to Sepsis
- In the nasopharynx areas can spread to respiratory tract and cause infections like acute febrile pharyngitis, acute respiratory disease or viral pneumonia
- Overreaction from immune system to tackle this can lead to sepsis
Describe the main features of community-acquired pneumonia Streptococcus pneumoniae
- primary disease in healthy patient or secondary to a predisposing factor such as chronic lung disease, diabetes mellitus, or malignancy
- Caused by tree pneumoniae, haemophilias influenza, staph.aureus
- Common x-ray patterns are lobar consolidation(dense area by border of Lung segment or lobe)bronchopneumonia consolidation (patchy dense areas around larger airways) and interestitial(fine shadowing in lung fields w/o sputum)
Understand the mechanism by which micro-organisms trigger the inflammatory cascade
- Cells sense, capture, process and then present antigens from microbe
- This triggers adaptive immunity to get either a humoral response(extracellular) or cell-mediated immunity
Outline the humoral response and cell-mediated immunity
Humoral response- antibodies
Cell mediated immunity - cytotoxic T cell response
COME BACK TO
Describe features of antigen presenting cells
- Strategic location - mucosal membrane, skin, blood, lymph nodes, spleen
- Diversity in pathogen capture mechanisms - phagocytosis(whole microbe), macropinocytosis(soluble particles)
- Diversity in pathogen sensors(PRRs)- extracellular pathogens(bacteria, fungi, Protozoa), intracellular(viruses)
Describe the role of MHC molecules in relation to microbe presentation
- Binds to antigen in order to form an antigen presenting cell in immune system
- Class 1 - expressed on all nucleated cells
- Class 2 - expressed on APCs
Describe the processing and presentation of microbial antigens to T lymphocytes
Exogenous pathway
Microbes captures via phagocytosis or micropinocytosis and degraded into peptides the endosome
The peptides in the vesicle bind with vesicles containing MHC class 2 molecules and form a complex
Only occurs in APCs which present to CD4+ molecules on T cells
Endogenous pathway Viral protein in cytosol marked for destruction by protea some Proteasome-generated viral peptide transported to ER by TAP proteins to form peptide-MHC class 1 complex Occurs in all cell types to present to CD8+ receptors on T cells
