Microcirculation Flashcards
Name downstream markers of perfusion
- Lactate concentration and lactate clearance
- Base deficit
- Oxygen consumption (VO2), venous oximetry (ScvO2, SmvO2), oxygen extraction ratio
- Nicotinamide adenine dinucleotide ratio (NADH:NAD)
- Gastric or sublingual tonometry (tissue pCO2)
- Gastric mucosal pH
- Tissue oxygen hemoglobin oxygen saturation (near infrared spectroscopy)
- Visualization of microcirculation with intravital microscopy
What are 3 major roles of the endothelial glycocalyx
- Regulation of transvascular fluid flux
- Regulation of intercellular interactions (regulation of leukocyte and platelet activation)
- Mechanotransduction, adjustment of vasomotor tone to shear stress
Explained the revised Starling’s law
The oncotic pressure gradient happens between the plasma and the subglyceal space (vs. plasma and interstitial in classic Starling’s law).
There is always very little proteins in the subglyceal space.
There is no reabsorption of interstitial fluid in the intravascular compartment caused by an increase in plasma osmotic pressure (only situation of reabsorption is with very acute drop in hydrostatic pressure, and it is very transient).
The fluid filtered to the interstitium is returned to the systemic circulation by lymphatic drainage.
What are the mediators of endothelial glycocalyx degradation
- Sheddases (enzymes lysing specific components of the glycocalyx): matrix metalloproteases, heparanases, hyaluronidases
- ROS
- LPS
- Thrombin and plasmin
Unclear mechanism of activation, suspect mediated by TNF-alpha, catecholamines +/- ANP
What are causes of endothelial glycocalyx degradation
- Hemorrhagic shock
- Sepsis
- Inflammatory cytokines –> shedding effect on ESL allows margination of leukocytes into tissue (adaptive response) –> can become maladaptive in critical illness
- IV fluid therapy
- Ischemia-reperfusion injury
- Oxidative injury
- Bacteria
- Natriuretic peptides
- (+/- Hyperglycemia, liver disease)
What are the 4 types of loss of hemodynamic coherence at the level of the microcirculation
- Microvascular shunts (heterogeneous blood flow due to inflammation)
- Hemodilution (decreasing O2 transport)
- Stasis (from vasopressors, compression by veins distended from fluid therapy)
- Increased diffusion distances (due to edema)
Name 2 methods of in vivo microcirculation visualization
- OPS: orthogonal polarization spectral imaging
- SDF: sidestream darkfield microscopy
What are the main components of the endothelial surface layer
- Proteoglycans (syndical, glypican)
- Glycosaminoglycans (heparan sulfate, hyaluronan, chondroitin sulfate)
- Soluble proteins (albumin)
- Glycoproteins (integrins, etc.)
What is the perfused boundary region (PBR) and how can it be used to assess the endothelial surface layer (ESL)
- Region of lateral movement of RBCs towards the endothelium (visualized by sidestream darkfield microscopy)
- Inversely proportional to ESL width
Equation of lymph flow
QL = (Pint + Pump - Psv)/RL
Pint = interstitial hydrostatic pressure
Ppump = driving pressure generated by intrinsic contraction and extrinsic compression of lymphatic vessels
Psv = systemic venous pressure
RL = resistance to lymph flow
Name and explain briefly 5 mechanisms of edema formation
- Venous hypertension (heart failure, thrombosis): causes regional or generalized increase in microvascular hydrostatic pressure which increases filtration +/- altered lymph flow which decreases drainage
- Hypoproteinemia: decreases oncotic pressure and increases filtration
- Increased microvascular permeability: increase in water permeability or surface area increases the filtration coefficient / increase in protein permeability decreases the osmotic reflection coefficient and the ability of the oncotic pressure to retain fluid.
Can be caused by inflammation which will trigger vasodilation (increased surface) and increased permeability. - Impaired lymph flow: decreases drainage (more pronounced in anesthetized patients –> anesthetic agents reduce lymphatic pumping)
- Changes in interstitial pressure-volume relationship: more negative interstitial pressure for a same volume which increases filtration.
Phenomenon seen with inflammation and immune-mediated disease, mostly in the skin and tracheal mucosa.
True or false: The severity of edema is directly proportional to the magnitude of venous pressure in crease, but there is a non-linear relationship between edema severity and hypoproteinemia.
True
Explain the constants in Starling’s equation
- K = filtration coefficient ->depends on water permeability of endothelium and microvascular surface area
- σ = protein permeability (osmotic reflection coefficient) -> 0 when membrane freely permeable to proteins and 1 when impermeable. Depends on tissues (1 in brain, 0 in liver)
Starling’s equation
Jv = K[(Pc-Pi) - s(pc-pi)]
Jv = fluid movement (mL/min)
Kf = constant (filtration coefficient, depends on water permeability and microvascular surface area) (mL/min⋅mm Hg)
Pc = capillary hydrostatic pressure (mmHg)
Pi = interstitial hydrostatic pressure (mmHg)
s = protein reflection coefficient
pc = capillary oncotic pressure (mmHg)
pi = interstitial oncotic pressure (mmHg)
*
Jv positive = filtration (net fluid movement out of the capillary)
Jv negative = absorption (net fluid movement into the capillary)
What is the contribution of albumin vs globulin to colloid osmotic pressure
Albumin and associated electrolytes provides 60-70% of oncotic pressure, globulins provide 30-40%
What are the consequences of EG degradation?
- Increased capillary permeability –> capillary leak, protein loss (further exacerbates capillary leak), edema
- Disturbed blood flow
- Increased leukocyte adhesion to endothelial cells + GAGs –> systemic inflammation + exhaustion of immune system and increased sensitivity to infections
- Free heparin sulfate –> penetration into the brain en sepsis induced encephalopathy
- Platelet adhesion to endothelial cells –> DIC
- Anticoagulant release
- Loss of vasomotor reactivity
