Module 4: Chapters 36-43
Hemodynamics:
Review the circulatory system and cardiac output regulation.
Hemodynamics is the study of the movement of blood throughout the circulatory system, along
with the regulatory mechanisms and driving forces involved. Concepts introduced here provide
additional understanding of drugs that affect the cardiovascular system.
The circulatory system has two primary functions: (1) delivery of oxygen, nutrients, hormones,
electrolytes, and other essentials to cells; and (2) removal of carbon dioxide and metabolic
wastes from cells. In addition, the system helps fight infection.
The circulatory system has two major divisions: the pulmonary circulation and the systemic
circulation. The pulmonary circulation delivers blood to the lungs. The systemic circulation
delivers blood to all other organs and tissues. The systemic circulation is also known as the
greater circulation or peripheral circulation.
• Arteries transport blood under high pressure to tissues.
• Arterioles are control vessels that regulate local blood flow.
• Capillaries are the sites for exchange of fluid, oxygen, carbon dioxide, nutrients,
hormones, and wastes.
• Venules collect blood from the capillaries.
• Veins transport blood back to the heart. In addition, veins serve as a major reservoir for
blood.
The circulatory system Blood vessels include:
is composed of the arteries, arterioles,
heart and blood capillaries, venules, and
vessels. veins.
Veins are less muscular
Arteries are muscular and stretch 6-10 times
and don’t stretch easy more than arteries
large increases in small increases in
arterial pressure only venous pressure cause
result in small increases large increases in vessel
in arterial diameter. diameter and increase
in venous volume.
,Blood moves within vessels because the force that drives the flow is greater than the resistance
present. Resistance to flow is determined by the diameter and length of the vessel and by
blood viscosity. From a pharmacologic viewpoint, the most important determinant of resistance
is vessel diameter: the larger the vessel, the smaller the resistance. Accordingly, when vessels
dilate, resistance declines, causing blood flow to increase; and when vessels constrict,
resistance rises, causing blood flow to decline. To maintain adequate flow when resistance rises,
blood pressure must rise as well.
CO=HR x SV
Cardiac Output Regulation:
HR is controlled by the Autonomic Nervous System.
Rate is increased by B1 adrenergic receptors in the SA node.
Rate is decreased by the parasympathetic branch via muscarinic
receptors in the SA node.
Parasympathetic impulses reach the heart through the vagus
nerve.
SV is determined by 3 factors: myocardial
contractility, cardiac afterload, and cardiac preload.
Myocardial contractility is the force with which the ventricles
contract.
Preload is the tension or stretch applied to the muscle before
contraction
Afterload is what must be overcome by the muscle contraction
Starling Law of the Heart
CO: According to the equation, an increase in HR or SV will increase CO, whereas a decrease in
HR or SV will decrease CO. For the average person, heart rate is about 70 beats/min and stroke
volume is about 70 mL. Multiplying these, we get 4.9 L/min—the average value for CO.
Myocardial contractility is defined as the force with which the ventricles contract. Contractility
is determined primarily by the degree of cardiac dilation, which in turn is determined by the
amount of venous return. The importance of venous return in regulating contractility and SV is
discussed separately later. In addition to regulation by venous return, contractility can be
increased by the sympathetic nervous system, acting through β1-adrenergic receptors in the
myocardium.
Preload is formally defined as the amount of tension (stretch) applied to a muscle before
contraction. In the heart, stretch is determined by ventricular filling pressure—that is, the force
of venous return: the greater filling pressure, the more the ventricles will stretch. Cardiac
preload can be expressed as either end-diastolic volume or end-diastolic pressure. As discussed
later, an increase in preload will increase SV, whereas a decrease in preload will reduce SV.
,Frequently the terms preload and force of venous return are used interchangeably—although
they are not truly equivalent.
Afterload is formally defined as the load against which a muscle exerts its force (i.e., the load a
muscle must overcome in order to contract). For the heart, afterload is the arterial pressure that
the left ventricle must overcome to eject blood. Common sense tells us that if afterload
increases, SV will decrease. Conversely, if afterload falls, SV will rise. Cardiac afterload is
determined primarily by the degree of peripheral resistance, which in turn is determined by the
constriction and dilation of arterioles. That is, when arterioles constrict, peripheral resistance
rises, causing AP (afterload) to rise as well. Conversely, when arterioles dilate, peripheral
resistance falls, causing AP to decline.
The Starling law states that the force of ventricular contraction is proportional to muscle fiber
length (up to a point). Accordingly, as fiber length (ventricular diameter) increases, there is a
corresponding increase in contractile force.
Venous return is the primary
determinant of SV and therefore CO
With regard to pharmacology, the
systemic filling pressure (the force
that returns blood to the heart) is
our most important factor.
Blood volume and venous tone can be altered by
drugs resulting in increased or decreased venous
return.
An increase in PR or CO will increase AP, whereas a decrease in PR or CO will decrease AP.
Peripheral resistance is regulated primarily through constriction and dilation of arterioles.
, Diuretics: Have 2 major implications
Treatment of HTN
Mobilization of edematous fluid associated with heart failure, cirrhosis, or kidney
disease.
Review anatomy and site of diuretic action----TEST QUESTION
The basic functional unit of the kidney is the nephron. The nephron has four functionally
distinct regions: (1) the glomerulus, (2) the proximal convoluted tubule (PCT), (3) the loop of
Henle, and (4a, 4b) the distal convoluted tubule.
The kidney serves three basic functions: (1) cleansing of extracellular fluid (ECF) and
maintenance of ECF volume and composition; (2) maintenance of acid–base balance; and (3)
excretion of metabolic wastes and foreign substances (e.g., drugs, toxins). Of the three,
maintenance of ECF volume and composition is the one that diuretics affect most.
Effects of the kidney on ECF are the net result of three basic processes: (1) filtration, (2)
reabsorption, and (3) active secretion.
• Filtration occurs at the glomerulus and is the first step in urine formation. Virtually all
small molecules (electrolytes, amino acids, glucose, drugs, metabolic wastes) that are
present in plasma undergo filtration. In contrast, cells and large molecules (lipids,
proteins) remain behind in the blood. The most prevalent constituents of the filtrate are
sodium ions and chloride ions. Bicarbonate ions and potassium ions are also present, but
in smaller amounts. This is a nonselective process, so filtration does not regulate
composition of urine.
• More than 99% of the water, electrolytes, and nutrients filtered at the glomerulus
undergo reabsorption. This conserves valuable constituents of the filtrate while allowing