Sepsis
How an infection at one site can set off a dysregulated response throughout the body, why leaky, dilated vessels and patchy microcirculation starve cells of oxygen, and how this causes organ dysfunction and septic shock.
By the end, you can
- Describe how innate immunity normally contains an infection at its source.
- Explain what makes the host response in sepsis dysregulated, and link a source of infection to systemic effects.
- Explain how endothelial activation causes vasodilation, capillary leak and microthrombi.
- Relate circulatory and microcirculatory failure to a raised lactate and septic shock.
- Relate the mechanism to dysfunction of the lungs, kidneys, brain, liver, clotting and heart.
- Recognise the Sepsis-3 definitions, the classic post-mortem findings and the key tests and numbers of sepsis, and explain how antimicrobials, source control, fluids, vasopressors and corticosteroids act on its mechanism.
What it is
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The infection starts the process, but the organ damage comes largely from the body’s own response; bacteraemia (bacteria in the blood) is neither necessary nor sufficient.
2 types to tell apart
- Sepsis
- Infection with new organ dysfunction, recognised by a change in measures such as breathing, consciousness, blood pressure, urine output, platelets or bilirubin.
- Septic shock
- The subset with circulatory and cellular changes severe enough to raise the risk of death substantially: persistent hypotension together with a raised lactate.
US spelling: bacteraemia → bacteremia, tumour → tumor.
Normal function
Containing an infection at its source
Most infections stay local. In the lung, patrol the and engulf microbes. Like neutrophils and endothelial cells, they carry pattern-recognition receptors, such as Toll-like receptors, that detect molecules common to microbes (pathogen-associated molecular patterns) and molecules released by damaged cells.
Recognition triggers cytokines such as tumour necrosis factor (TNF), interleukin-1 and interleukin-6. Locally they make nearby vessels dilate and leak and draw in neutrophils: the redness, heat and swelling of inflammation, confined to the site. Anti-inflammatory signals then damp the response as the microbes are cleared.
Everywhere in the body the microcirculation of arterioles, and venules delivers oxygen to cells. Healthy endothelium keeps the blood fluid, adjusts vessel tone and holds plasma inside the vessels.
Underlying change · Step 1 of 5
From a source of infection to a dysregulated response
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
The endothelium is activated and injured
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Vasodilation, leak and septic shock
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Patchy microcirculation and starved cells
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Organ dysfunction
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .