Pathophysiology Flashcards
Coagulation
3 phases - initiation, amplification, propagation
Initiation:
- Exposed collagen binds PLT and vWF
- Exposed TF binds FVII - which activates FIX and FX
- End result = Va, VIIa, IXa, Xa
Amplification
- Prothrombinase (Va/Xa) and Tenase (VIIIa/IXa) formed
- Tenase activates Xa
- Prothrombinase catalyses Thrombin (II) formation
Propagation
- Thrombin burst leads to fibrin production
- Also generates more Va and VIIIa (for prothrombinase and tenase)
- And XIIIa, which crosslinks fibrin
Inflammation
A pathophysiological mechanism of host defence against harmful stimuli
Tissue injury and infection leads to release of PAMPs and DAMPs
Cells recognise these and release inflammatory mediators, including:
- TNFa
- Il-1
- Il-6
Leading to vasodilation, increased capillary permeability, fever and leucocyte chemotaxis
Outcome is either resolution or chronicity
Trauma-induced coagulopathy
Impaired clot formation
- Activated protein C
- Autoheparinisation from glycocalyx degradation
- Consumptive coagulopathy
- Hypothermia and acidosis
- Haemodilution
Dysregulation of fibrinolysis
- Hyperfibrinolysis
- Fibrinolysis shutdown
Impaired platelet function
- Unclear mechanism ?due to DAMPs
Wound healing
Haemostasis
- as per clotting cascase - initiation, amplification, propagation
- formation of clot
Inflammation
- PLT release PDGF and TGFb
- Neuts and macrophages phagocytose foreign material and bacteria
Proliferation
- Epithelial, endothelial cells and fibroblasts proliferate
- Wound closes by contraction
- Strength is 10% at 1 week and 70% at 3 months
Remodelling
- Takes place over months to years
Reperfusion syndrome
Restoration of blood flow to ischaemic area results in:
- Generation of reactive oxygen species
- And inflammatory infiltrate, leading to
- Endothelial damage
- Cytokine production and
- Toxic metabolites (K+, lactate, myoglobin) washout into systemic circulation
- > SIRS and MODS
Anaphylaxis
Exaggerated systemic response to allergen, characterised by vasodilation, vascular permeability, smooth muscle spasm and cellular infiltrate
An example of type 1 hypersensitivity
Driven by IgE binding to allergen and activating mast cells and basophils, with release of primary mediators (histamine, bradykinin, prostaglandins) and secondary mediators (leukotrienes).
DIC
Acquired consumptive coagulopathy characterised by microvascular thrombosis leading to organ dysfunction.
Exposure of blood to procoagulant susbtances (TF) leads to widespread coagulation and tissue ischaemia. Depletion of clotting factors leads to bleeding.
Diagnosis includes
- Low plt
- Low fibrinogen
- Increased PT and APTT
- Increased D-Dimer
- Schistocytes (haemolysed red cells)
Metastatic cascade
Invasion into basement membrane Intravasation Survival in circulation Extravasation Colonisation
Suture duration
Monocryl - 50% strength at 2 weeks
PDS - 50% at 4 weeks
Vicryl - 50% strength at 3 weeks
Vicryl Rapide
Maxon - 60% at 4 weeks
Shock
A state of systemic hypoperfusion.
3 broad phases:
- Compensated
- Decompensated/reversible
- Irreversible
Multiple aetiologies, broadly classified as:
- Obstructive
- Distributive
- Hypovolaemic
- Cardiogenic
Common pathophysiology is cellular hypoxia due to inadequate oxygen delivery. This leads to:
- Cell membrane ion pump dysfunction
- Intracellular oedema
- Leakage of cellular contents
- Inadequate regulation of cellular pH
This progresses on the systemic level leading to:
- Acidosis
- Lactataemia
- Endothelial dysfunction
- Inflammation
This is compounded by neurohumoral mechanisms to defend central end-organ perfusion at the expense of peripheral perfusion.
- Sympathetic activation and vasoconstriction
- Renin-angiotensin-aldosterone system
MODS
= Alteration in 2 or more organs’ function such that homeostasis cannot be maintained
May be primary (due to inciting tissue injury) or secondary (due to host response)
Quantified by SOFA score • CNS - GCS • Cardiovascular – hypotension, inotrope requirement • Coagulation - platelets • Renal - creatinine • Respiratory - paO2/FiO2 • Liver – bili All scored from 0 - 4
SIRS
- Injury leads to production of proinflammatory cytokines (Il-1, Il-2, Il-6, TNFa)
- These cause fever, sympathetic stimulation, RAS activation, coagulation and complement activation and vasoactive compound release
- Consequent endothelial damage and vascular permeability leads to organ dysfunction
Suture duration
Monocryl
- 50% at 3 weeks
- Absorbed in 3 months
PDS
- 70% at 2 weeks, 50% at 4 weeks
- Absorbed at 6-8 months
Vicryl (Polyglactin)
- 75% strength at 2 weeks, 50% at 3 weeks
- Absorbed in 3 months
Maxon
- similar to PDS
Chromic gut:
- loses strength in 10-14 days
- digested by 2-3 months
Atherosclerosis
- Inciting events include proinflammatory substances in the vasculature, including glycated Hb and LDLs, and shear forces from turbulent blood flow (eg at junctions)
- Endothelial injury leads to accumulation of lipid-laden macrophages.
- Platelet aggregation, fibroblast and smooth muscle activation leads to a raised lesion with a fibrous cap, calcification, lipid-rich necrotic core and intimal smooth muscle hypertrophy
Sepsis definition
“clinical syndrome of organ dysfunction, caused by dysregulated host response to infection”
All sepsis has organ dysfunction by definition
SIRS has fallen out of fashion
qSOFA
quick Sequential Organ Function Assessment
RR >22
Altered mentation
Systolic BP <100
2 or more = high risk
Used to predict mortality, NOT to diagnose sepsis (according to 2017 surviving sepsis guidelines)
SOFA
= Sequential Organ Failure Assessment
6 organ systems scored from 0-4 (C3 R2 L)
- Resp - Pa02/Fi02
- Coag - platelets
- Liver - bili
- Cardio - MAP/vasopressor
- CNS - GCS
- Renal - creatinine or urine output
Score of 2 or more suggests presence of organ dysfunction
Dysfunction in 2 or more = MODS
