September 30, 2015
Cardiovascular 6
Special Circulations: Cardiac Muscle
• The coronary arteries branch directly from the aorta, and provide
the perfusion of the heart. Although blood actually is pumped
through the heart, only ~ 100 µm of the inner endocardial
surface can obtain significant amounts of nutrition directly from
the blood supply in the cardiac chambers.
Special Circulations: Cardiac Muscle
• Blood flow through the coronary capillaries during systole and
diastole is different than in most other tissues of the body. The
blood flow to the ventricles falls during systole, and increases
during diastole. During ventricular contraction, blood flow
through the capillaries is obstructed by compression of the
vessels. Thus, blood flow increases during diastole when the
muscle around the vessels relaxes.
Special Circulations: Brain
 The cerebral circulation is almost completely
insensitive to neural and hormonal influences that
produce vasoconstriction elsewhere in the body. By
far the predominant factor that controls blood flow
through the cerebral circulation is paracrine release.
In particular, carbon dioxide has a strong
vasodilation effect on the cerebral vessels.
Special Circulations: Skeletal Muscle
 Control of blood flow to skeletal muscle is in many respects
similar to that in the heart. Paracrine factors have strong
influences, and vasodilation is induced by the release of
epinephrine from the adrenal gland.
 A major difference between the two circulations is that
skeletal muscle arterioles are richly innervated by sympathetic
vasoconstrictor fibers, and are major resistance vessels to
contribute to total peripheral resistance.
 Because skeletal muscle mass is so large, vasodilation of
muscle vessels would greatly diminish total peripheral
resistance unless vasoconstriction occurs in other vascular
beds.
 It is thus necessary that the central nervous system provides
control of blood flow through skeletal muscle.
Special Circulations: Skin
 The skin requires little blood flow to meet its metabolic
needs. However, blood flow to the skin increases
tremendously when the body is overheated.
 Many arteriovenous shunts exist in the skin, and these are
innervated by sympathetic efferents. When temperature is
high, the efferents stop firing, and more blood travels into the
skin for cooling. When temperature is low, the opposite
occurs.
 Bradykinin release during sweating also leads to vasodilation
of vascular smooth muscle in the skin, allowing more blood
to be cooled.
Where is Fluid Located in the Body?
Plasma
Interstitial fluid
Intracellular fluid
(~ 3 L)
(~12 L)
(~25 L)
Anatomy of a Capillary
• Capillaries are composed of a single layer of endothelial cells and a
basement membrane.
• Small intercellular clefts typically separate the endothelial cells.
• Capillaries are often associated with elongated, highly branched cells
that form a meshlike layer between the endothelium and interstitial
fluid. These cells are called pericytes. The pericytes contribute to
restricting capillary permeability.
Movement of Materials Across Capillaries
•
Exchange of materials through capillaries usually occurs through
diffusion.
•
Small and uncharged and lipid-soluble molecules (including O2
and CO2) have no problem passing through the capillary wall.
•
Larger and charged molecules may pass through the intercellular
clefts or via vesicular transport.
•
Some capillaries have receptors for particular proteins; once the
protein binds it is carried across the membrane via a process
called transcytosis.
Movement of Materials Across Capillaries
•
Water crosses the capillary through specialized water
channels (aquaporins) in the endothelial cell membrane.
Movement of Materials Across Capillaries
•
In general, large molecules have a very difficult time
escaping from capillaries, unless they are lipophylic.
Movement of Materials Across Capillaries
• Large molecules and even whole cells can enter
and leave the circulation when intercellular clefts
are large.
Osmosis
• Osmosis is the diffusion of water molecules
across a semi-permeable membrane from a
region of high concentration to a region of
low concentration until a state of dynamic
equilibrium is reached.
• A molecule is osmotically active if it causes
osmosis to occur.
Osmolarity
• A measure of the absolute concentration of
osmotically active particles.
• A solution of 1 mole/L of non-dissociable
solute is equivalent to 1 osmole/L (1 Osm).
• Normal osmolarity of body fluids is about
300 mOsm.
• The osmotic pressure of a 1 Osm solution is
22.4 Atm, or 22.4 x 760 = 17,024 mmHg.
Thus a 300 mOsm solution has an osmotic
pressure equivalent of 17,024 x 0.3 = 5,107
mmHg.
Oncotic Pressure
• Defined as the osmotic pressure generated by
protein.
• Protein is the only molecular species for which
there is a significant concentration difference
between the plasma and interstitial fluid (higher in
plasma).
• Hence, differences in protein concentration provide
the only osmotic driving force at the capillary level.
• The plasma protein concentration is about 7
gm/100 cc plasma (7 gm%). The osmotic pressure
generated by this protein is known as the oncotic
pressure and is in the range of 25-28 mmHg.
Hydrostatic Pressure
• Another major force is at play in capillaries:
hydrostatic pressure, which is due to the pressure
in the blood imparted primarily by the contraction
of the ventricle.
• The hydrostatic pressure is higher in the capillary
than in the interstitial fluid, and tends to force fluid
OUT of the capillary.
• The balance between oncotic pressure and
hydrostatic pressure across the capillary will
determine whether there is a net gain or loss of
fluid across the vessel. This balance can be
expressed quantitatively via: Starling’s equation.
Starling Equation
Jv = Kf ([Pc—Pi] — σ [πc—πi])
Net
fluid
movement
Oncotic
Pressure
difference
Filtration
coefficient
Hydrostatic
pressure
difference
Reflection
coefficient
Starling Equation
Jv = Kf ([Pc—Pi] — σ [πc—πi])
If Jv is positive, fluid leaves the capillary
(filtration)
If Jv is negative, fluid enters the capillary
(absorption)
Starling Equation
Jv = Kf ([Pc—Pi] — σ [πc—πi])
•
•
•
The filtration coefficient ( Kf ) is the
constant of proportionality.
A high Kf value indicates a highly water
permeable capillary. A low value
indicates a low capillary permeability.
The filtration coefficient is the product of
two components: capillary surface area
and capillary hydraulic conductance (the
number of aquaporin channels present).
Starling Equation
Jv = Kf ([Pc—Pi] — σ [πc—πi])
•
•
•
•
The reflection coefficient (σ) is often thought of as a
correction factor.
Some smaller proteins can leak across the capillary
membrane through the intercellular clefts, which must
be accounted for as it diminishes the driving force.
The reflection coefficient is used to ‘correct for’ the
ineffectiveness of some of the oncotic pressure
gradient.
It can have a value from 0 up to 1.
Non-fenestrated vessels have a reflection coefficient
close to 1, whereas the value is lower for fenestrated
capillaries.
Starling Equation
Jv = KXf ([Pc—Pi] — σ
X [πc—πi])
Kf and σ are fixed for most (but not all)
capillaries. Thus, changes in Jv are only
due to changes in the oncotic pressure and
changes in the hydrostatic pressure across
the vessel.
Jv ≈ ([Pc—Pi] — [πc—πi])
Starling Equation
Arteriole
Capillary
Venule
Filtration
Jv ≈ ([Pc—Pi] — [πc—πi])
25 -3
25
5
Jv ≈ ([25 J—
8 — [ 25 — 5])
v ≈-3]
Starling Equation
Arteriole
Venule
Absorption
Jv ≈ ([Pc—Pi] — [πc—πi])
25 -3
10
25
2
Jv ≈ -7
5
Arteriole
Venule
Filtration
Jv ≈ 8
Absorption
Jv ≈ -7
The net filtration pressure is 1 mmHg. In
general, we tend to lose 2-4 liters of fluid
per day into the interstitial space due to the
2
filtration-absorption imbalance.
Increased Venous Pressure
Arteriole
Venule
J ≈ ([60 — (-3)] — [25 — 5])
v
J ≈ ([40 — (-3)] — [25 — 5])
v
J ≈
v
J ≈
v
43
23
Filtration occurs across the entirety of the
capillary; considerable fluid is lost into the
interstitial space!
2
Hypoproteinemia
Arteriole
Venule
J ≈ ([25 — (-3)] — [11— 2])
v
J ≈ ([10 — (-3)] — [11— 2])
v
J ≈
v
J ≈
v
19
4
Filtration occurs across the entirety of the
capillary; considerable fluid is lost into the
interstitial space!
2
Increased Capillary Permeability
Assume 40% increase in Kf
Arteriole
J ≈ 1.4 * ([25 — (-3)] — [25 — 5])
v
J ≈
v
11.2
Venule
J ≈ 1.4 *([10 — (-3)] — [25 — 5])
v
J ≈
v
-9.8
The net filtration pressure increases to 1.4;
more loss of fluid into the interstitial space!
2
Hemorrhage
Arteriole
J ≈ ([15— (-3)] — [25 — 5])
v
J ≈ -2
v
Venule
J ≈ ([5— (-3)] — [25 — 5])
v
J ≈ -12
v
Consequently, fluid is absorbed from the
interstitial space into the intravascular
compartment. Over time, this movement of
fluid will serve to increase blood volume,
thereby increasing blood pressure. 2
Test your understanding!
The main determinants of mean capillary hydrostatic
pressure are:
a)
b)
c)
d)
e)
Arterial pressure and venous pressure
Arterial pressure and capillary permeability
Pre-capillary resistance and capillary permeability
Pre-capillary resistance and venous pressure
Venous pressure and capillary permeability
Question for
Discussion
Do changes in
hematocrit
posture
affect
affect
plasma
fluid
movement
oncotic
pressure?
across
capillaries?
The Lymphatic System
 Because filtration typically exceeds absorption
in capillaries, there is a net loss of fluid (about
2-3 L/day) into the interstitial space. It is the job
of the lymphatic system to collect this fluid and
return it to the circulation. Other functions
include picking-up materials in the liver and
intestine, and serving as a filter to capture and
destroy foreign pathogens.
Lymphatic System

In addition to the
capillaries of the
cardiovascular system,
an extensive collection
of lymph capillaries
exists in the body.
These lymph capillaries
are close to “real”
capillaries in all tissues
of the body, except the
central nervous system
and kidney.
Lymphatic System
 The thin walls of the
lymph capillaries are held
open by attachments to
surrounding cells.
Adjacent cells overlap in
the lymph capillaries,
providing valves that
allow fluid and large
molecules in the
interstitial space to enter
(but not to leave).
Lymphatic System
 The lymph capillaries coalesce to
form larger “collecting”
lymphatics, the largest of which is
the thoracic duct, which empties
fluid from the entire lower body
back into the cardiovascular
system. The lymphatic system
makes connections with the
cardiovascular system near the
collarbones, near the junction
between the subclavian veins and
the internal jugular veins.
Lymphatic System
 The major force driving fluid to enter the lymph capillaries is
interstitial fluid pressure (once the fluid is inside the lymphatic
system, it is called lymph). The higher the pressure in the
interstitial fluid, the more fluid will enter the lymph capillaries. This
arrangement is convenient, as it helps to assure that all the fluid
leaving the cardiovascular system is returned.
 Fluid flow into lymph capillaries will increase under any of the
following conditions that raise interstitial fluid pressure:
o Capillary pressure is elevated (which enhances filtration)
o Plasma colloid osmotic pressure is reduced (which retards
absorption)
o Interstitial fluid protein is increased (which retards
absorption)
o Capillary permeability is increased
Lymphatic System
 No pump moves fluid in the
lymphatic system. The
major force inducing lymph
movement comes from
compression of lymph
vessels during muscular
contraction (if a limb is
immobilized, you have to
elevate it because muscular
contraction is not sufficient
to induce lymph flow).
Lymphatic System
 Edema results when interstitial fluid builds up in an area.
This often happens after injury because of increases in
the amount of protein in the interstitial space (which pulls
fluid from the cardiovascular system). Although increased
interstitial pressure usually leads to increased lymphatic
drainage, this doesn’t happen after some injuries because
lymph capillaries are also damaged. Furthermore, there
are limits to the rate of fluid flow into the lymphatic
system.
 Another factor that can lead to edema is blockage of the
lymphatic system. In elephantiasis, for example, lymph
vessels are blocked by parasites, which compromises
fluid drainage.
Lymphatic System
 As noted above, the hydrostatic pressure in the interstital
space is slightly negative. This is largely due to the
presence of the lymphatic system, and the movement of
fluid into this system. As long as the interstital pressure is
negative, no edema will occur.
 In addition to removing fluid, the lymphatic system is a
conduit for protein to leave the interstitial space. Without
the actions of the lymphatic system, the oncotic gradient
between the plasma and interstital space would equalize,
which would contribute to the development of edema.
Changes in Plasma Osmolarity and Cell Size
• Most capillaries are highly permeable
to small ions such as Na+ and Cl- and
water.
• Although cell membranes normally
are quite selective about the ions that
enter or leave, and actively maintain
very low intracellular Na+ levels
through Na+/K+ ATPase, they are
freely permeable to water.
• As a result, a sudden change in the
osmolarity of the plasma can result in
water entering or leaving body cells,
thereby causing them to expand or
shrink.
Example: Infusion of Hypertonic Saline
Hypertonic
Saline
H2
O
H2
O
• Intravenous delivery of hypertonic saline
results in the osmolarity of the
intravascular space being higher than the
interstital space.
• Consequently, water leaves the
interstitial space (osmosis) until the
water concentration on the two sides of
the capillary are equal.
• As a result, the water concentration is
higher in the intracellular space than in
the interstitial space, and water leaves
the cell.
Cell
Shrinks • Due to the loss of fluid, the cell shrinks.
Example: Infusion of Hypotonic Saline
Hypotonic
Saline
H2
O
H2
O
• Intravenous delivery of hypotonic saline
results in the osmolarity of the interstitial
space being lower than the intravascular
space.
• Consequently, water leaves the capillary
(osmosis) until the concentration on the
two sides is equal.
• As a result, the water concentration is
higher in the interstitial space than in the
intracellular space, and water enters the
cell.
• Due to the gain of fluid, the cell expands.
Cell
Expands • Rapid infusion of hypotonic saline can
cause red blood cells to explode!