Cardiac Output

Cardiac OutputCardiac output is the volume of blood pumped by the heart per minute (mL blood/min). Cardiac output is a function of heart rate and stroke volume. The heart rate is simply the number of heart beats per minute. The stroke volume is the volume of blood, in milliliters (mL), pumped out of the heart with each beat. Increasing either heart rate or stroke volume increases cardiac output. Cardiac Output in mL/min = heart rate (beats/min) X stroke volume (mL/beat) An average person has a resting heart rate of 70 beats/minute and a resting stroke volume of 70 mL/beat. The cardiac output for this person at rest is:Cardiac Output = 70 (beats/min) X 70 (mL/beat) = 4900 mL/minute.The total volume of blood in the circulatory system of an average person is about 5 liters (5000 mL). According to our calculations, the entire volume of blood within the circulatory sytem is pumped by the heart each minute (at rest). During vigorous exercise, the cardiac output can increase up to 7 fold (35 liters/minute)

Control of Heart Rate

The SA node of the heart is enervated by both sympathetic and parasympathetic nerve fibers. Under conditions of rest the parasympathetic fibers release acetylcholine, which acts to slow the pacemaker potential of the SA node and thus reduce heart rate. Under conditions of physical or emotional activity sympathetic nerve fibers release norepinephrine, which acts to speed up the pacemaker potential of the SA node thus increasing heart rate. Sympathetic nervous system activity also causes the release of epinephrine from the adrenal medulla. Epinephrine enters the blood stream, and is delivered to the heart where it binds with SA node receptors. Binding of epinephrine leads to further increase in heart rate.

Control of Stroke Volume Under conditions of rest, the heart does not fill to its maximum capacity. If the heart were to fill more per beat then it could pump out more blood per beat, thus increasing stroke volume. Also, the ventricles of the heart empty only about 50% of their volume during systole. If the heart were to contract more strongly then the heart could pump out more blood per beat. In other words, a stronger contraction would lead to a larger stroke volume. During periods of exercise, the stroke volume increases because of both these mechanisms; the heart fills up with more blood and the heart contracts more strongly.

Stroke volume is increased by 2 mechanisms:

1. increase in end-diastolic volume

2. increase in sympathetic system activity

End-diastolic Volume An increase in venous return of blood to the heart will result in greater filling of the ventricles during diastole. Consequently the volume of blood in the ventricles at the end of diastole, called end-diastolic volume, will be increased. A larger end-diastolic volume will stretch the heart. Stretching the muscles of the heart optimizes the length-strength relationship of the cardiac muscle fibers, resulting in stronger contractility and greater stroke volume.

Starling's Law

Starling's Law describes the relationship between end-diastolic volume and stroke volume. It states that the heart will pump out whatever volume is delivered to it. If the end-diastolic volume doubles then stroke volume will double.

An Increase in Sympathetic Activity Increases Stroke VolumeThe cardiac muscle cells of the ventricular myocardium are richly enervated by sympathetic nerve fibers. Release of norepinephrine by these fibers causes an increase in the strength of myocardiall contraction, thus increasing stroke volume. Norepinephrine is thought to increase the intracellular concentration of calcium in myocardial cells, thus facilitating faster actin/myosin cross bridging. Also, a general sympathetic response by the body will induce the release of epinephrine from the adrenal medulla. Epinephrine, like norepinephrine will stimulate an increase in the strength of myocardial contraction and thus increase stroke volume.

Blood VolumeFluid Exchange Betweem Capillaries and Tissues

Capillaries are composed of a single layer of squamos epithelium surrounded by a thin basement membrane. Most capillaries (except those servicing the nervous system) have pores (spaces) between the individual cells that make up the capillary wall. Plasma fluid and small nutrient molecules leave the capillary and enter the interstitial fluid through these pores, in a process called bulk flow. Bulk flow facilitates the efficient transfer of nutrient out of the blood and into the tissues. However, blood cells and plasma proteins, which are too large to fit through the pores, do not filter out of the capillaries by bulk flow.

Together, blood plasma and interstitial fluid make up the extracellular fluid (ECF). Plamsa constitutes 20%, while interstitial fluid constitutes 80% of the ECF. The distribution of extracellular fluid between these two compartments is determined by the balance between two opposing forces: hydrostatic pressure and osmotic pressure.

The beating of the heart generates hydrostatic pressure, which, in turn, causes bulk flow of fluid from plasma to interstitial fluid through walls of the capillaries. In other words, the pressure in the system forces plasma to filter out into the interstitial compartment. The composition of the interstitial fluid and the plasma is essentially the same except that plasma also contains plasma proteins not found in the interstitial fluid. Because of the presence of plasma proteins, the plasma has a higher solute concentration than does the interstitial fluid. Consequently, osmotic pressure causes interstitial fluid to be absorbed into the plasma compartment. In other words, the plasma proteins drive the reabsorption of water back into the capillaries via osmosis.

The magnitudes of filtration and absorption are not equal. The net filtration of fluid out of the capillaries into the interstitial compartment is greater than the net absorption of fluid back into the capillaries. The excess filtered fluid is returned to the blood stream via the lymphatic system. In addition to its roles in digestion and immunity, the lymphatic system functions to return filtered plasma back to the circulatory system. The smallest vessels of the lymphatic system are the lymphatic capillaries (shown in yellow). These porous, blind-ended ducts form a large network of vessels that infiltrate the capillary beds of most organs. Excess interstitial fluid enters the lymphatic capillaries to become lymph fluid.

Lymphatic capillaries converge to form lymph vessels that ultimately return lymph fluid back to the circulatory system via the subclavian vein. The presence of one-way valves in the lymph vessels ensures unidirectional flow of lymph fluid toward the subclavian vein.

If excess fluid cannot be returned to the blood stream then interstitial fluid builds up, leading to swelling of the tissues with fluid, this is called edema.

Causes of Edema1. Reduced concentration of plasma proteins. When the concentration of plasma proteins drops, the osmotic potential of plasma drops, thus less interstitial fluid is absorbed into the capillaries. The rate of filtration, however, remain unchanged. Therefore, the ratio of filtration to absorption increases, leading to a build up of interstitial fluid. Any condition that would lead to a reduction in plasma proteins could potentially cause edema. Examples of conditions that reduce plasma proteins include:

Kidney disease can result in the loss of plasma proteins in the urine.

Liver disease can decrease the synthesis of plasma proteins.

A protein-deficient diet will decrease plasma proteins.

Severe burns result in a loss of plasma proteins (albumin) at the burn site

2. Increased capillary permeability. During an inflammatory response, tissue damage leads to the release of histamine from immune cells. Histamine causes an increase in the size of capillary pores. As capillaries become more permeable, the rate of filtration increases.

3. Increase in venous pressure. If venous pressure is increased then blood dams up in the upstream capillary bed, resulting in excess filtration. Examples of this condition include:

Left heart failure. The left half of the heart drains blood from the lungs. When the left ventricle fails to adequately pump blood, venous pressure in the lungs increases. This increase in hydrostatic pressure causes an increase in the rate of filtration of fluid out of the capillaries and into the interstitial compartment. As a result, the lungs fill with fluid, a condition called, pulmonary edema.

Standing still. If one stands still for long period of time, then blood will pool in the veins of the legs. This will increase venous pressure and lead to weeping of fluid into the tissues. You can actually feel your feet swell if you stand motionless for a long time.

4. Blocked Lymphatics. If lymph vessels become blocked, then lymph fluid will not be drained from the effected area and the area will swell. Any condition that causes blockage or removal of lymph vessels can lead to edema. Examples of this condition include:

Filaria round worms are transmitted to humans by some species of mosquitos. The worms migrate to the lymph vessels and block them. This causes dramatic swelling of the effected area, a condition called elaphantiasis.

Treatment for breast cancer may include removal of lymph vessels from breast and arms. This is done to limit the metastasis (spread) of cancerous cells to other parts of the body through the lymph. Removal of lymph vessels results in swelling of the effected area.

Regulation of Blood Volume by the Kidneys

The kidneys filter the blood and eliminate excess water and metabolic wastes by producing and excreting urine. The daily volume of urine produced by the kidneys affects the amount of ECF in the body and thus has a direct influence on blood volume. If the kidneys retain water then blood volume rises. However, if the kidneys excrete large amounts of water then the blood volume will decrease.

The regulation of water excretion by the kidneys is controlled, in large part, by antidiuretic hormone (ADH). In the presence of ADH, the kidneys retain water. In the absence of ADH the kidneys excrete more water. ADH is produced by the hypothalamus and secreted by the posterior pituitary gland. The hypothalamus contains osmoreceptors that directly monitor the osmolality of plasma. Plasma osmolality is high when plasma volume is low. Osmoreceptors detect this condition and signal for the secretion of ADH. Retention of water by the kidney restores blood volume to normal. ADH has the added effect of stimulating thirst. Thus when your body needs water you are driven to seek water.