06b: Microcirculation Flashcards
Two primary roles of capillaries.
- Deliver nutrients to tissues
2. Carry metabolites away from tissues
Vasomotion refers to waxing/waning of (X), to increase/decrease flow to (Y).
X = arteriolar tone Y = downstream capillaries
Fewer open capillary beds means (smaller/larger) diffusion distance.
Larger
Fick’s Law of Diffusion state that (X) is equal to:
X = Bulk Flow
D)(A)(deltaC/deltaX
Fick’s law: bulk flow increases with increase in which components?
- D (diffusion coefficient, which decreases with higher MW)
- A (surface area)
- DeltaC (concentration gradient)
Fick’s law: bulk flow increases with decrease in which components?
DeltaX (diffusion distance or path length)
The diffusion coefficient is inversely related to:
Square root of MW
Fick’s Law can be written with permeability as a factor. What’s the equation?
J = PAdeltaC
Diffusion of gases such as O2 and CO2 is primarily controlled by (X), since it takes about (Y) portion of their transit time through capillaries for exchange/equilibration to occur.
X = blood flow through capillary Y = 1/3
T/F: D for O2 is high, but relatively lower for CO2
False - high for both
Certain substances, such as (X) can only enter/exit capillaries through intercellular junctions. This limits the movement, because the junctions are (Y)% of total capillary (Z).
X = glucose, AA Y = 0.2-0.4 Z = surface area
T/F: for most nutrients, diffusion is sufficient as major mechanism to supply tissues.
True
If capillary wall is 0.3 micrometers thick, what’s the (deltaX) value in Fick’s Law?
Unknown - path of molecule not in straight line
Establishing and empirical relationship, using (X), solves the path/distance problem in Fick’s Law. (X) tells us how far molecule will move per (Y).
X = Permeability Y = unit time, unit concentration/pressure gradient, and per surface area
Substance moves through intercellular junction in capillary. It will have (easier/harder) time clearing its path of (X) if it’s a large molecule.
Harder;
X = fluid
(Blood/interstitium) contains high protein concentration with low permeability (proteins can’t leave). Thus, it exerts (X) pressure, which is (in sync/opposed to) hydrostatic pressure.
Blood;
X = oncotic
Opposed to
For bulk flow through capillary, which key pressure gradients should be considered?
Hydrostatic and Oncotic
If net hydrostatic pressure is greater than net oncotic pressure in capillaries, which direction is net fluid movement?
Out of capillaries
If net hydrostatic pressure is less than net oncotic pressure in capillaries, which direction is net fluid movement?
Into capillaries
Hydraulic permeability is defined as (X).
X = permeability of membrane to water
If hydrostatic pressure of interstitial fluid was negative, it would favor which movement?
Favor fluid movement out
Hydrostatic P is initially about (X) mmHg in capillary. If the value is about 4 mmHg in interstitial fluid, what’s the net hydrostatic P? Fluid moves (out/in) as it passes capillary bed.
X = 40;
Net: 36 mmHg
Can’t decide until you know net oncotic P
T/F: Oncotic P in interstitial fluid is 0 mmHg.
False - there is some protein in IF
T/F: Amount of protein in interstitial fluid depends on the tissue.
True
Oncotic P is initially about (X) mmHg in capillary. If the value is about 5 mmHg in interstitial fluid, what’s the net oncotic P? Net hydrostatic is 36 mmHg. Fluid moves (out/in) as it passes capillary bed.
X = 25
Net: 20 mmHg
Out
Net fluid loss out of capillaries per day is 2-4L. But we don’t lose all that fluid. Where is it going?
Lymphatics recaptures it (back to circulation)
T/F: Bulk flow is enough to meet our glucose needs.
False - net filter only 2-5g/day, but we use 400g/day
List the two main causes of edema.
- Increase in net filtration pressure (high hydrostatic/low oncotic P in capillaries)
- Blockage of lymphatics
- Increase in hydraulic permeability
Hypoproteinemia will (increase/decrease) (hydrostatic/oncotic) P of (IF/capillaries), causing net filtration (in/out).
Decrease;
Oncotic;
Capillaries
Out (EDEMA)
Bug bite causes local edema. Briefly explain why.
Toxin released that increases hydraulic permeability of capillaries
Intercellular junctions in semipermeable membrane allow passage of (polar/nonpolar) molecules.
Water and small, polar solutes
Glycocalyx lining (luminal/basal) surface of endothelial cells serves which function?
Luminal;
Prevents protein escape
Beta-2 agonists (increase/decrease) permeability of endothelial junction complex. What’s the mechanism?
Decrease;
Increase cAMP, which increases junctional strands
Inflammation (increase/decrease) permeability of endothelial junction complex. What’s the mechanism?
Increases;
Phosphorylates beta-catenin and VE-cadherin (weakens tight junctions and facilitates extravasation of WBC)
Growing, healing, or chronically hypoxic tissue secretes (X), which stimulates (Y) growth and (increases/decreases) endothelial permeability.
X = VEGF;
Y = microvascular
Increases
(Gap/tight) junctions allow rapid transmission of (X) signaling. If the signaling is between neighbor cells, it’s (Y) signaling. What’s the other type?
Gap;
X = chemical and electrical
Y = homo-cellular
Hetero-cellular (between endothelium and underlying vascular smooth m)
eNO is a (short/long)-lived modulator of (X). It’s synthesized by (Y) in response to:
Short;
X = vascular tone
Y = eNOS (from L-Arg)
- Shear stress
- Agonists (ACh)
- Adenosine
- VEGF (hypoxia)
- Serotonin
eNO causes (vasodilation/vasoconstriction) and (increases/decreases) organ perfusion.
Vasodilation;
Increases
eNO (contracts/relaxes) smooth muscle. One way it does this by binding and (inhibiting/activating) (X) enzyme. Then…
Relaxes;
Activating
X = guanylyl cyclase
Increase cGMP, activate PKG, phosphorylation of substrates promotes relaxation
eNO (contracts/relaxes) smooth muscle. One way it does this is by (activating/inhibiting) (X) channels. This causes (Y).
Activating;
X = big conductance K channels
Y = hyper polarization (and vascular relaxation)
EDHFs, aka endothelium-derived (X), are produced in response to (Y) and (increase/decrease) smooth muscle excitability/contraction.
X = hyper polarization factors;
Y = agonists (bradykinin)
Decrease
Prostacyclin is produced in response to (X) situation(s). It (increases/decreases) cAMP in smooth muscle, facilitating (Y) release.
X = inflammation, shear stress
Increases;
Y = eNO
Most potent vasoconstrictor in body is (X). It’s released on (luminal/basal) side in response to agents such as (Y).
X = Endothelin;
Basal;
Y = Angiotensin II and ADH
Under low BP circumstances, you’d expect (eNO, EDHF, Endothelin) to be released.
Endothelin
T/F: Endothelin effect, like eNO, is short-lived.
False - long-lasting effect (2-3 hours contraction of vascular bed)
Thrombin plays which two roles in regulation of hemostasis?
- Increase vWF exocytosis (platelet adhesion)
2. Increase eNO and prostacyclin production (inhibit platelet aggregation)
Increased endothelial Ca influx causes (eNO, EDHF, Endothelin) to be released.
eNO and EDHFs
Inflammatory agonists (increase/decrease) (P/E)-selectin movement to endothelial surface.
Increase
P-selectin
(X) in inflamed tissue increase (P/E)-selectin, which acts for several hours to sustain “stickiness” of endothelial surface.
X = cytokines (IL1, TNF, interferon gamma)
E-selectin
During “arrest” of leukocytes in inflammatory response, endothelium begins to express (X) molecules and leukocytes express (Y) molecules.
X = ICAM and VCAM Y = beta-integrins
Diapedesis/Emigration of leukocytes is primarily dependent on high expression of (X) molecules.
X = ICAM and PECAM
There’s increasing evidence that atherosclerosis formation may be tied to (X) dysfunction, such as imbalance between (Y) and (Z).
X = vascular endothelial Y = eNO Z = endothelin
(Endothelin/eNO) pays protective role on vascular beds, such as decreasing lesion formation. It does this by which mechanism(s)?
eNO;
- Inhibit expression of selectins/CAMs
- Less smooth muscle proliferation
- Inhibits platelet aggregation
You’d expect (eNO/Endothelin) circulating levels to be higher in patients with atherosclerosis. And in pulmonary hypertension?
Endothelin higher in both cases
Oxidative LDLs are thought to up regulate (eNO/endothelin) production by binding (X).
Endothelin;
X = LOX-1 receptor on endothelium
(X) binding (Y) also produces superoxide anion, which inactivates (eNO/endothelin).
X = Ox-LDL and/or platelets
Y = LOX-1
eNO
List some diseases/states that increase LOX-1 receptor.
HT, diabetes, hyperlipidemia, increased Ox-LDL
(X) enzyme, which normally mediates endothelial quiescence via (Y) production, can switch its function to produce (Z).
X = eNOS Y = eNO Z = ROS/H2O2 (promote inflammation)
