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Circulation Part 2

Capillaries

Capillaries are the sites of material exchange between blood vessels and tissue. The
exchange is mostly a function of diffusion (remember Fick's Law).

Capillaries - very thin wall, 1 m thick (human hair is 100 m). It is a single layer of cells,
which have no smooth muscle and no connective tissue.

The diameter of a typical capillary is 7 m. The diameter of a RBC is 8 m. Branching of
capillaries is so extensive that it is estimated that no cell is more than 100 m from a
capillary.

There are 10-40 billion capillary beds with a surface area of 600 m2.

Only about 5% of total blood volume (250 ml out of 5000ml) is in the capillary beds.

The volume of blood in contact with the surface of all capillaries is equivalent to one pint of
fluid covering a basketball court.

Flow Rate - volume of blood flowing through a given segment of circulatory system per unit
of time.

Since the circulatory system is closed, CO = flow rate. CO in humans is 5L/min therefore
there the flow rate through capillaries is 5L/min.

Velocity of Flow - linear speed with which blood flows through a given segment of the
circulatory system. While the flow rate is constant throughout the circulatory system, the
velocity of flow is variable.

Flow Rate
Velocity of Flow =
Total Cross Section Area of Vessels

The total cross section of capillaries is 1300x greater than cross section of the aorta.
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Exchange

Lipids and gases can diffuse through the cell membranes.

Other substances such as certain proteins can be transported via vesicles.

Some water-soluble molecules can diffuse down their concentration gradient through pores
between endothelial cells of the capillaries. The sizes of the pores vary from tissue to
tissue and the pores can also change size, depending upon the metabolic state of the
tissue. Histamine affects pore size, it makes them larger.

There are no pores in brain and spinal cord capillaries. This is called the blood brain
barrier.
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Pericytes

Pericytes are vascular mural cells embedded in the basement membrane of blood
microvessels. They extend their processes along capillaries, pre-capillary arterioles and post-
capillary venules. There are many types of pericytes. CNS pericytes are uniquely positioned
in the neurovascular unit between endothelial cells, astrocytes and neurons. They integrate,
coordinate and process signals from their neighboring cells to generate diverse functional
responses that are critical for CNS functions in health and disease, including regulation of the
blood–brain barrier permeability, blood retina barrier permeability, angiogenesis, clearance of
toxic metabolites, capillary hemodynamic responses, neuroinflammation and stem cell
activity.
Pericytes function a similar way in non-nervous tissue playing roles in blood flow regulation
in small blood vessels and capillaries. Pericytes have contractile proteins that can respond to
vasoactive molecules including neurotransmitters. Like in nervous tissue, they are involved in
angiogenesis, clearance of toxic metabolites, inflammation and stem cell activity.
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The pericyte density varies between different organs and vascular beds, and the proportion of
the endothelial abluminal surface that is pericyte covered varies as well. The central nervous
system (CNS) vasculature is generally regarded as being the most pericyte covered, with a
1:1–3:1 ratio between endothelial cells and pericytes, and an approximately 30% coverage of
the abluminal surface. Significantly lower ratios have been reported for some other tissues,
e.g., human skeletal muscle. Blood vessels of the retina has the highest abundance of
pericytes. A conservative estimate based on available information is that endothelial -to-
pericyte ratios in normal tissues vary between 1:1 and 10:1 and that pericyte coverage of the
endothelial abluminal surface ranges between 70% and 10%. Mesangial cells in the
glomerulus of the kidney are pericytes.

Many pathologies affect pericyte function. An example of this would be diabetes. Pericyte
numbers associated with nervous tissue are reduced with diabetes leading to hemorrhaging,
alteration of blood gas equilibration and other metabolic consequences, one of which is
oxidative stress (free radical formation). One of the consequences of this pathological process
is diabetic nerve pain.

Diabetes Mellitus: Hyperglycemia increases blood viscosity by increasing plasma fibrinogen.

This increases embolitic stroke by 2-4x. It also increases free radial generation, ROS. Also
causes lactic acidosis and keto acidosis. These processes are particularly damaging to blood
vessels causing atherosclerosis/arteriosclerosis. The results of these cause localized ischemic
conditions, poor wound healing and tissue necrosis.

https://www.sciencedirect.com/science/article/pii/S1534580711002693
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Capillary Transit Time Heterogeneity (CTH)
Normally not all capillary beds are perfused equally. Increase in blood flow (hyperaemia)
can cause an increase in homogenous blood flow.
Abnormal increase in CTH could hamper efficient oxygen extraction in tissue.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351434/
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Metarterioles are shunts.

In the non-working muscle, only about 10% of the capillaries are open.
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Extra Cellular Fluid (ECF)

Interstitial Fluid

Circulating Plasma

Movement of CO2 and O2 and glucose is a function of concentration gradients. CO2 and O2
simply pass through the cell membrane down their concentration gradients, glucose,
however, does not easily pass through cell membranes. It goes down its concentration
gradient via carrier mediated transport mechanism.
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Two basic forces determine fluid movement in and out of capillaries:

Hydrostatic pressure - net hydrostatic pressure of a capillary bed and its surrounding tissue
is the difference between capillary blood pressure, which is the hydrostatic pressure from
inside the capillary pushing out, and interstitial fluid hydrostatic pressure (PIF), which is
from the interstitial fluid pushing into the capillary.

Osmotic pressure - net osmotic pressure of a capillary bed and its surrounding tissue is the
difference between plasma colloid osmotic pressure (P), aka oncotic pressure, which
is a function of the number of particles in the plasma, and interstitial fluid colloid
osmotic pressure, which is a function of the number or particles in the interstitial fluid.
The final movement of fluid either in or out of the capillary is the sum of all of these forces.

Ultrafiltration - movement of fluid from the capillaries to interstitial fluid.

Reabsorption - movement of fluid from the interstitial fluid to capillaries.

Note that the rate at which water molecules diffuse through the capillary membrane is about
80x faster than linear flow rate.
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Starling Equilibrium: amount of fluid filtered out at beginning of the capillary is

approximately equals amount of fluid filtering in at end of the capillary

What is the purpose of fluid movement in the capillaries?

It plays an essential role in regulating the distribution of ECF between plasma and interstitial
fluid.

Maintenance of proper arteriole blood pressure depends in part on an appropriate volume of

circulating blood.

If plasma volume , then reabsorption will be greater than ultrafiltration, yielding a net
movement of fluid into the capillaries.

If plasma volume , then ultrafiltration will be greater than reabsorption, yielding a net
movement of fluid out of the capillaries.
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Lymphatics

Typical net pressure for ultrafiltration is 11 mmHg, which yields 20L/day of ultrafiltrate.
Typical net pressure for reabsorption is 9 mmHg for reabsorption, which yields 17L/day of
reabsorption. This results in a net loss of fluid from the capillaries to the interstitial fluid (3
L/day).

Where does this excess fluid go?

Lymphatic capillaries absorb the excess fluid and return it to the blood.
The lymphatic circulatory system is low pressure. Lymph vessels have one way valves, like
some veins, and are surrounded by smooth muscles, which contract rhythmically.

Lymphatic system is important for:

-Immune System

-Transport of large fat molecules

-Returns of filtered proteins

Edema

4 General Causes of Edema

1) Reduced concentration of plasma proteins.

2) Increased permeability of capillary walls.

3) Increased venous pressure.

During pregnancy, the enlarged uterus compresses the veins of the abdominal cavity.
This increases venous pressure in the lower extremities leading to swelling (edema)
of legs and feet.

4) Blockage of lymph vessels.

Filariasis - mosquito borne parasite which blocks lymph vessels. Causes

elephantiasis.