Microcirculation and Blood Flow

Into the capillaries now! I'll also be answering the question I raised in my last post about why sympathetic input doesn't shut off your circulation when you're in panic mode.

List the component vessels of the microcirculation.

The microcirculation is made out of arterioles, venules, capillaries, metarterioles and arteriovenous shunts. You've probably heard of the first three, so I'll just describe the last two. Metarterioles, which go directly between arterioles and venules, are like wide capillaries with a little bit of smooth muscle. Capillaries can branch off the metarterioles. Arteriovenous shunts are abnormal connections between arteries and veins. These normally do not cause too much issue unless large arteries and veins are involved.

Describe transport of different classes of substances across the capillary wall.

Substances can be transported between or through cells. Transport can be active (requiring energy), or passive (down gradients). Reasonably small lipid-soluble substances can diffuse directly through the cell wall and small-medium sized water-soluble substances can diffuse between cells, though larger substances may require other processes such as pinocytosis. Plasma proteins do not usually cross the capillary wall.

Describe the Starling Equilibrium.
Define colloidal osmotic pressure.

The Starling Equilibrium describes the movement of fluid across the capillary membrane.

First, I'll describe the two inward pressures (i.e. interstitial fluid -> capillaries), as they are pretty much constant over the length of the capillaries. One of the inward pressures affecting reabsorption of fluid into the capillaries is the hydrostatic pressure of the interstitial fluid, though this makes only a small contribution (<1 mmHg). The major inward pressure is actually the colloid osmotic pressure caused by the proteins in the blood- as the proteins do not leave the capillaries, the osmolarity of the blood is higher than that of the interstitial fluid, causing water to diffuse back into the capillaries. This accounts for around 25mmHg of inward pressure (i.e. nearly all of it).

The outward pressures are a little trickier, as one of them does change over the length of the capillaries. I'll start with the one that doesn't change that much: colloid osmotic pressure of the interstitial fluid. As I just mentioned, few proteins leak out into the interstitial fluid, so there shouldn't be many proteins there to draw the water over. Hence, this hardly makes any contribution to the outward pressure. Most of the outward pressure is from the hydrostatic pressure of the capillary fluid. This is highest at the start of the capillary before any of the blood has left the capillary, but decreases over the length of the capillary as fluid diffuses out. As you go down the length of the capillary, eventually the outward pressure will decrease below the inward pressure, and hence there will be a switch from ultrafiltration (capillaries -> interstitial fluid) to reabsorption (interstitial fluid -> capillaries).

Predict how changes in plasma protein, blood pressure or vaso-tone will alter plasma and interstitial volume.

As I mentioned earlier, plasma proteins are important in colloid osmotic pressure, which is the major inward pressure causing fluid to become reabsorbed. Hence, decreasing plasma protein causes less fluid to be reabsorbed, so more fluid remains in the tissues, causing swelling. This is why severely malnourished children might have big bellies- not enough fluid gets reabsorbed, causing swelling in the tissues around the belly.

As for blood pressure (which is regulated by vaso-tone), blood pressure directly affects the hydrostatic pressure of the capillary fluid. Hence an increase in blood pressure will push more fluid out of the capillaries into the interstitial fluid. When blood pressure decreases, less fluid is pushed out.

Describe the functional role of the lymphatic system.

Although reabsorption occurs towards the end of the capillaries, not all of the blood that is filtered is reabsorbed. This leaves some excess which must be drained off in some way, otherwise our tissues would swell. This fluid is picked up by vessels of the lymph system and eventually dumped into the brachiocephalic veins, as mentioned previously. Without a working lymph system, you might get elephantitis, which is a condition characterised by lots of swelling (oedema).

Describe how changes in arteriolar resistance distribute cardiac output.

As mentioned in my previous post, arterioles can constrict and reduce their diameters, reducing blood flow through them. This shunts blood through arteries that haven't been constricted.

Define Hyperaemia, Active hyperaemia, Reactive hyperaemia and Ischaemia.

• Hyperaemia: Increased blood flow.
• Ischaemia: Reduced blood flow.
• Active hyperaemia: Increased blood flow due to activity.
• Reactive hyperaemia: Hyperaemia following ischaemia. (If you constrict blood flow to an area for a while, and then suddenly stop constricting it, you will temporarily get more blood flow than normal to that area.) The magnitude and duration of reactive hyperaemia is proportional to the magnitude and duration of the preceding ischaemia

Describe the role of local metabolites in regulation of blood flow.
List the actions of O2, CO2, Adenosine, K+and H+ on local vascular resistance.

Yay, now I'll finally get to tell you why blood flow to muscles etc. increases during exercise, even though the sympathetic nervous system constricts the arterioles!

When skeletal muscles are working hard, they use more energy and produce more waste products. These waste products can cause vasodilation. This effect overrides the vasoconstriction caused by the sympathetic nervous system. Metabolites do not work on the muscle directly- they are detected by the endothelial cells lining the blood vessel, which then act on the smooth muscle in a paracrine fashion. Here are some of the metabolites that can cause vasodilation:

• CO₂ - has the opposite effect in the pulmonary circulation. (O₂ is the opposite: it causes vasoconstriction everywhere except for in the pulmonary circulation.)
• H⁺ - pH decreases as CO₂ is acidic. Also, lactic acid produced during anaerobic respiration is acidic.
• K⁺ - due to an increased number of action potentials. Usually the Na⁺/K⁺ pump restores Na⁺ and K⁺ levels following an action potential, but it can't do this when there are too many action potentials. Cell death due to insufficient blood flow or whatever can also cause an increase in potassium levels, as potassium is released from cells when they die.
• Adenosine- released in response to increased metabolic activity, especially in the heart.

In addition to these, nitric oxide released by endothelial cells in response to shear stress can also cause vasodilation. (Nitric oxide also causes vasodilation during an erection.)

Another important point to note is that vasoconstriction does not occur everywhere in the first place. You see, vasoconstriction occurs due to adrenaline or noradrenaline meeting α₁-adrenergic receptors on arteriolar smooth muscle. Arteries supplying the brain do not have these receptors, and thus cannot be constricted by the sympathetic nervous system. This is important, because it is always vital that the brain has blood.

Define remodelling and angiogenesis in relation to long term control of blood flow.

The mechanisms that I just described are useful for short-term regulation of blood flow. Long-term, remodelling and angiogenesis (growth of new blood vessels) can regulate blood flow. It is hypothesised that these processes are triggered by changes in oxygen tension (partial pressure?). Hormones that mediate this process include endothelial cell growth factor (ECGF), fibroblast growth factor (FGF) and angiogen.