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Transcript
Discuss the mechanisms underlying the process of fluid exchange at the
capillaries.
Capillary walls are composed of a single endothelial cell layer and is leaky
to most substances except plasma proteins. For most vascular beds, the
endothelial cells are attached to one another at their margins. A continuous
basement membrane encircles the periluminal surface of all the capillaries,
providing additional support. The plasma membrane contains a variety of
specific pathways through which ions and other water solutes can be
transported between blood and interstitial fluid. Most of the exchange occurs
by diffusion however between the cells especially in the case of lipid soluble
substances such as oxygen and carbon dioxide. The exchanges require a
relatively permeable wall however to drive blood through the circulation
requires relatively high hydrostatic pressures. As a consequence, some fluid
moves by bulk flow from capillary to interstitial fluid in a process called
ultrafiltration. This fluid must be reabsorbed back into the circulation to
maintain blood flow and most is reabsorbed by osmosis and the rest by the
lymphatic system. As plasma proteins are too large to cross the capillary
wall, they produce an effective colloid osmotic pressure. The concentration
difference between the plasma and interstitial fluid for proteins is about
16mmHg. However, proteins are negatively charged and therefore attract
diffusible cations and repel anions. This results in a slightly uneven
distribution of ions, contributing another 9mmHg to the osmotic pressure of
the plasma. Hence the total is 25mmHg. The hydrostatic pressure is about
32mmHg in the arterioles and 15mmhg at the venular end. The net
hydrostatic pressure gradient in the interstitial fluid forces fluid out of the
capillaries by ultrafiltration, a force which is greater at the arteriolar end than
at the venular end. Osmotic pressure remains constant along the length of the
capillary however. At the arteriolar end, the net difference between the two
forces cause fluid to leave the capillary however at the venular end the
difference causes reabsorption with fluid returning to the capillary. This
balancing of ultrafiltration and osmosis is referred to as the Starling
equilibrium. There is slightly more ultrafiltration than osmosis and the small
amount of fluid lost in the interstitium is removed by the lymphatic system.
What is oedema? Briefly outline two possible causes of oedema.
If ultrafiltration in the capillary is excessive, the volume of interstitial fluid
increases. When clinically detectable this is called oedema. It can be local to
an organ or widespread. It can be caused by chronic right heart failure which
leads to an elevated capillary pressure. Also an elevated venous blood
pressure as occurs in the lower limbs when in the standing position can be
enough to cause oedema in some people.
What major changes occur in blood flow distribution during strenuous
exercise? How are these changes produced?
At the onset of exercise, signals are transmitted not only from the brain to
the muscles to cause muscle contraction but also into the vasomotor center
to initiate mass sympathetic discharge throughout the body. Simultaneously,
the parasympathetic signals to the heart are attenuated. Therefore, three
major circulatory effects result.
First, the heart is stimulated to greatly increased heart rate and increased
pumping strength as a result of the sympathetic drive to the heart plus
release of the heart from normal parasympathetic inhibition.
Second, most of the arterioles of the peripheral circulation are strongly
contracted, except for the arterioles in the active muscles, which are strongly
vasodilated by the local vasodilator effects in the muscles by acetylcholine
secreting sympathetic fibers. Thus, the heart is stimulated to supply the
increased blood flow required by the muscles, while at the same time blood
flow through most nonmuscular areas of the body is temporarily reduced,
thereby temporarily "lending" their blood supply to the muscles. This
accounts for as much as 2 L/min of extra blood flow to the muscles, which is
exceedingly important when one thinks of a person running for his life-even
a fractional increase in running speed may make the difference between life
and death. Two of the peripheral circulatory systems, the coronary and
cerebral systems, are spared this vasoconstrictor effect because both these
circulatory areas have poor vasoconstrictor innervation-fortunately so
because both the heart and the brain are as essential to exercise as are the
skeletal muscles.
Third, the muscle walls of the veins and other capacitative areas of the
circulation are contracted powerfully, which greatly increases the mean
systemic filling pressure. This is one of the most important factors in
promoting increase in venous return of blood to the heart and, therefore, in
increasing the cardiac output.
Describe the mechanisms underlying intrinsic control of blood flow in the
vasculature.
Many organs demonstrate the phenomenon of autoregulation. This means
that despite large changes in perfusion pressure the blood flow remains
remarkably constant. This is determined to be a result of the response of the
arteriolar smooth muscle to stretch and local metabolites. According to the
law of Laplace, the smooth muscle of arterioles contracts when its wall
tension is passively increased and relax when the pressure decreases.
Increased wall tension opens calcium channels in the muscle and this
increases the muscle tone. The reduction in radius matches the increase in
perfusion pressure so that there is no change in blood flow. This is called
myogenic autoregulation and does not occur in the skin.
During increased metabolism there is a local decrease in the partial pressure
of oxygen, an increase in the partial pressure of carbon dioxide and an
increase in the H+ concentration in the interstitial fluid. These changes cause
the smooth muscle to relax to a degree that is appropriate to the increased
metabolism and ensure an increase in flow with little to no change in
perfusion pressure. This called metabolic regulation or active hyperemia.
Increases in temperature and in the concentrations of ATP, ADP, AMP,
adenosine, inorganic phosphate, lactate and pyruvate as well as potassium
concentration and interstitial osmolarity can also cause vasodilation.
Nervous control is capable of over-riding metabolic regulation.
Discuss the regulation of cerebral blood flow.
Blood flow into the brain is fairly constant and does not change greatly with
a changing pressure gradient. The brain receives 13% of the cardiac output,
has a high O2 consumption and a large arteriovenous difference. However
the distribution of the blood can be altered to allow for different activities in
the brain e.g. thinking vs vision. Nervous control is not one of the key
regulators of cerebral blood flow. There is sparse sympathetic innervation in
the brain which has vasoconstrictor potential but has little effect when
activated. The same is true for activating the vasodilator nerves which
emerge from the Facial N (CNVII). The action of hormones is also
determined to have little effect. The effects of oxygen partial pressure have
been found to be more important. Below 50mmHg pO2 the cerebral
arterioles become sensitive to the vasodilating effects of hypoxia. The main
regulators of cerebral blood flow have been determined to be carbon dioxide
and hydrogen ions. Carbon dioxide combines with water to form carbonic
acid which can dissociate to hydrogen ions and bicarbonate. It has been
discovered that a rise in the partial pressure of carbon dioxide leads to
increased cerebral blood flow. This increase in pCO2 may cause the
concentration of hydrogen ions to increase as the two are linked by the
above reactions. Similarly, a decrease in pCO2 can cause a fall in cerebral
blood flow probably due to a fall in hydrogen ion concentration. A reduced
oxygen supply is accompanied by an increase in pCO2 and acidity, making
the determining factor to be hypercapnia not hypoxia.
Describe the changes that occur in the coronary circulation during
exercise.
The left and right coronary arteries emerge from the aortic sinuses. They
each supply the myocardium of the atria and ventricles and also provide a
blood supply to the SA and AV nodes. They flow into capillaries in the
myocardium, drained by coronary veins which return blood into the right
atrium via the coronary sinus. The heart receives 5% of the cardiac output
and has a very high oxygen consumption. The relationship between coronary
blood flow and the work of the heart is a linear one. That means that if one
increases so does the other. The increase in coronary blood flow can be seen
to be the result of two opposing forces. During the heart cycle, blood flow
through the coronary circulation is seen to decrease during systole. The
vessels are compressed during contraction and flow is particularly reduced
in the left coronary artery. In diastole there is no compression and blood
flow returns. In exercise, the heart rate is increased, tachycardia, and the
cardiac contractility is also increased. Tachycardia reduces the diastolic
filling time considerably and so less blood is able to reach the heart. The
increased contractility means greater compression and thus less blood flow
during systole. During increased cardiac activity, there is little further
decrease in the venous oxygen content and the increased demand is satisfied
by increased coronary blood flow. Hypoxia and adenosine are the main
vasodilators of the coronary arteries and these are in high concentration
during exercise. Thus although greater compression and shorter diastole in
exercise act to reduce coronary blood flow, the metabolic regulation that
occurs causes blood flow to increase during the diastolic period to supply the
greater oxygen and thus blood demand. The last remaining effect which
increases blood flow during exercise is increased potassium concentration in
the extracellular fluid. Each time the muscle cell is excited by an action
potential, the repolarization sees more potassium ions released into the ECF.
These ions act as vasodilators and so increase the blood flow in the nearby
coronary arteries. They have their greatest effect when the work of the heart
is increased as in the case of exercise.
Describe what happens to fluid movement across capillary walls when:
(a) arterioles constrict;
(b) plasma protein concentration is decreased.