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■ DEFINITION
Cardiac cycle is defined as the succession of (sequence of) coordinated events taking place
in the heart during each beat. Each heartbeat consists of two major periods called systole
and diastole. During systole, heart contracts and pumps the blood through arteries. During
diastole, heart relaxes and blood is filled in the heart. All these changes are repeated during
every heartbeat, in a cyclic manner.
■ EVENTS OF CARDIAC CYCLE
Events of cardiac cycle are classified into two:
1. Atrial events
2. Ventricular events.
■ DIVISIONS AND DURATION OF CARDIAC CYCLE
When the heart beats at a normal rate of 72/minute, duration of each cardiac cycle is about
0.8 second.
■ ATRIAL EVENTS
Atrial events are divided into two divisions:
1. Atrial systole = 0.11 (0.1) sec
2. Atrial diastole = 0.69 (0.7) sec.
■ VENTRICULAR EVENTS
Ventricular events are divided into two divisions:
1. Ventricular systole = 0.27 (0.3) sec
2. Ventricular diastole = 0.53 (0.5) sec.
In clinical practice, the term ‘systole’ refers to ventricular systole and ‘diastole’ refers to
ventricular diastole.
Ventricular systole is divided into two subdivisions and ventricular diastole is divided into
five subdivisions.
Ventricular Systole
1. Isometric contraction = 0.05 sec.
2. Ejection period = 0.22 sec.
Ventricular Diastole
1. Protodiastole = 0.04 sec.
2. Isometric relaxation = 0.08 sec.
3. Rapid filling = 0.11 sec.
4. Slow filling = 0.19 sec.
5. Last rapid filling = 0.11 sec.
Among the atrial events, atrial systole occurs during the last phase of ventricular diastole.
Atrial diastole is not considered as a separate phase, since it coincides with the whole of
ventricular systole and earlier part of ventricular diastole.
■ ATRIAL DIASTOLE
After atrial systole, the atrial diastole starts. Simultaneously, ventricular systole also starts.
Atrial diastole lasts for about 0.7 sec (accurate duration is 0.69 sec). This long atrial diastole
is necessary because, this is the period during which atrial filling takes place. Right atrium
receives deoxygenated blood from all over the body through superior and inferior venae
cavae. Left atrium receives oxygenated blood from lungs through pulmonary veins.
Atrial Events Vs Ventricular Events
Out of 0.7 sec of atrial diastole, first 0.3 sec (0.27 sec accurately) coincides with ventricular
systole. Then, ventricular diastole starts and it lasts for about 0.5 sec (0.53 sec accurately).
Later part of atrial diastole coincides with ventricular diastole for about 0.4 sec. So, the
heart relaxes as a whole for 0.4 sec.
■ DESCRIPTION OF VENTRICULAR EVENTS
■ ISOMETRIC CONTRACTION PERIOD
Isometric contraction period in cardiac cycle is the first phase of ventricular systole. It lasts
for 0.05 second. Isometric contraction is the type of muscular contraction characterized by
increase in tension, without any change in the length of muscle fibers. Isometric contraction
of ventricular muscle is also called isovolumetric contraction. Immediately after atrial
systole, the atrioventricular valves are closed due to increase in ventricular pressure.
Semilunar valves are already closed. Now, ventricles contract as closed cavities, in such a
way that there is no change in the volume of ventricular chambers or in the length of
muscle fibers. Only the tension increases in ventricular musculature. Because of increased
tension in ventricular musculature during isometric contraction, the pressure increases
sharply inside the ventricles.
First Heart Sound
Closure of atrioventricular valves at the beginning of this phase produces first heart sound.
Significance of Isometric Contraction
During isometric contraction period, the ventricular pressure increases greatly. When this
pressure increases above the pressure in the aorta and pulmonary artery, the semilunar
valves open. Thus, the pressure rise in ventricle, caused by isometric contraction is
responsible for the opening of semilunar valves, leading to ejection of blood from the
ventricles into aorta and pulmonary artery.
■ EJECTION PERIOD
Due to the opening of semilunar valves and isotonic contraction of ventricles, blood is
ejected out of both the ventricles. Hence, this period is called ejection period. Duration of
this period is 0.22 second. Ejection period is of two stages:
1. First Stage or Rapid Ejection Period
First stage starts immediately after the opening of semilunar valves. During this stage, a
large amount of blood is rapidly ejected from both the ventricles. It lasts for 0.13 second.
Second Stage or Slow Ejection Period
During this stage, the blood is ejected slowly with much less force. Duration of this period is
0.09 second.
End-systolic Volume
Ventricles are not emptied at the end of ejection period and some amount of blood
remains in each ventricle. Amount of blood remaining in ventricles at the end of ejection
period (i.e. at the end of systole) is called end-systolic volume. It is 60 to 80 mL per
ventricle.
Measurement of end-diastolic volume
Endsystolic volume is measured by radionuclide angiocardiography (multigated acquisition
– MUGA scan) and echocardiography. It is also measured by cardiac catheterization,
computed tomography (CT) scan and magnetic resonance imaging (MRI)
Ejection Fraction
Ejection fraction refers to the fraction (or portion) of end-diastolic volume that is ejected
out by each ventricle per beat. From 130 to 150 mL of enddiastolic volume, 70 mL is ejected
out by each ventricle (stroke volume). Normal ejection fraction is 60% to 65%.
Determination of ejection fraction
Ejection fraction (Ef) is the stroke volume divided by enddiastolic volume expressed in
percentage. Stroke volume (SV) is, enddiastolic volume (EDV) minus endsystolic volume
(ESV)
■ PROTODIASTOLE
Protodiastole is the first stage of ventricular diastole, hence the name protodiastole.
Duration of this period is 0.04 second. Due to the ejection of blood, the pressure in aorta
and pulmonary artery increases and pressure in ventricles drops. When intraventricular
pressure becomes less than the pressure in aorta and pulmonary artery, the semilunar
valves close. Atrioventricular valves are already closed. No other change occurs in the heart
during this period. Thus, protodiastole indicates only the end of systole and beginning of
diastole.
Second Heart Sound
Closure of semilunar valves during this phase produces second heart sound.
BOHR EFFECT
It is a phenomenon that arises from relationship between pH and oxygen’s affinity for
hemoglobin: A lower, more acidic pH promotes oxygen dissociation from hemoglobin. In
contrast, a higher, or more basic, pH inhibits oxygen dissociation from hemoglobin. The
greater the amount of carbon dioxide in the blood, the more molecules that must be
converted, which in turn generates hydrogen ions and thus lowers blood pH. Furthermore,
blood pH may become more acidic when certain byproducts of cell metabolism, such as
lactic acid, carbonic acid, and carbon dioxide, are released into the bloodstream.
The Bohr effect works both ways: An increase in H in blood causes O2 to unload from
hemoglobin, and the binding of O2 to hemoglobin causes unloading of Hfrom hemoglobin.
The explanation for the Bohr effect is that hemoglobin can act as a buffer for hydrogen ions
(H). But when Hions bind to amino acids in hemoglobin, they alter its structure slightly,
decreasing its oxygen-carrying capacity. Thus, lowered pH drives O2 off hemoglobin,
making more O2 available for tissue cells. By contrast, elevated pH increases the affinity of
hemoglobin for O2 and shifts the oxygen–hemoglobin dissociation curve to the left.
PHYSIOLOGICAL ROLE
The Bohr effect increases the efficiency of oxygen transportation through the blood. After
hemoglobin binds to oxygen in the lungs due to the high oxygen concentrations, the Bohr
effect facilitates its release in the tissues, particularly those tissues in most need of oxygen.
When a tissue's metabolic rate increases, so does its carbon dioxide waste production.
When released into the bloodstream, carbon dioxide forms bicarbonate and protons
through the following reaction:
Although this reaction usually proceeds very slowly, the enzyme carbonic anhydrase (which
is present in red blood cells) drastically speeds up the conversion to bicarbonate and
protons. This causes the pH of the blood to decrease, which promotes the dissociation of
oxygen from haemoglobin, and allows the surrounding tissues to obtain enough oxygen to
meet their demands. In areas where oxygen concentration is high, such as the lungs,
binding of oxygen causes haemoglobin to release protons, which recombine with
bicarbonate to eliminate carbon dioxide during exhalation. These opposing protonation and
deprotonation reactions occur in equilibrium resulting in little overall change in blood pH.
The Bohr effect enables the body to adapt to changing conditions and makes it possible to
supply extra oxygen to tissues that need it the most. For example, when muscles are
undergoing strenuous activity, they require large amounts of oxygen to conduct cellular
respiration, which generates CO2 (and therefore HCO3− and H+) as byproducts. These waste
products lower the pH of the blood, which increases oxygen delivery to the active muscles.
Carbon dioxide is not the only molecule that can trigger the Bohr effect. If muscle cells
aren't receiving enough oxygen for cellular respiration, they resort to lactic acid
fermentation, which releases lactic acid as a byproduct. This increases the acidity of the
blood far more than CO2 alone, which reflects the cells' even greater need for oxygen. In
fact, under anaerobic conditions, muscles generate lactic acid so quickly that pH of the
blood passing through the muscles will drop to around 7.2, which causes haemoglobin to
begin releasing roughly 10% more oxygen.
3. DIGESTIVE ENZYMES – THEIR
PRECURSORS,SUBSTRATES AND THE PRODUCTS
OF ACTION OF THE ENZYMES
Most dietary nutrients come in the form of large polymers that cannot be absorbed in the
intact state. They have to be hydrolyzed by enzymes in the gastrointestinal (GI) tract, and
the breakdown products, including monosaccharides, amino acids, and fatty acids, are
absorbed. The whole process of digestion consists of hydrolytic cleavage reactions.
Approximately 30g of digestive enzymes is secreted per day. Because each enzyme has a
fairly narrow substrate specificity and hydrolyzes only certain bonds,several enzymes have
to cooperate in the digestion of complex nutrients.
Enzymes Precurso Source Substrate Product
r
Saliva
Salivary Amylase Salivary Starches(Polysaccharide Maltose(disaccharide),
glands ) maltoriose(trisaccharide),
and alpha -dextrins
Lingual Lipase Lingual Triglycerides (fats and Fatty acids and
glands in oils) and other lipids diglycerides
the
tongue
Gastrc Juice
Pepsin (activated from Stomach Proteins Peptides
pepsinogen by pepsin chief cells
and hydrochloric acid)
■ COUNTERCURRENT MULTIPLIER
Loop of Henle
Loop of Henle functions as countercurrent multiplier. It is responsible for development of
hyperosmolarity of medullary interstitial fluid and medullary gradient.
Role of Loop of Henle in Development of Medullary Gradient
Loop of Henle of juxtamedullary nephrons plays a major role as countercurrent multiplier
because loop of these nephrons is long and extends upto the deeper parts of medulla. Main
reason for the hyperosmolarity of medullary
interstitial fluid is the active reabsorption of sodium chloride and other solutes from
ascending limb of Henle loop into the medullary interstitium. These solutes accumulate in
the medullary interstitium and increase the osmolarity.
Now, due to the concentration gradient, the sodium and chlorine ions diffuse from
medullary interstitium into the descending limb of Henle loop and reach the ascending limb
again via hairpin bend. Thus, the sodium and chlorine ions are repeatedly recirculated
between the descending limb and ascending
limb of Henle loop through medullary interstitial fluid leaving a small portion to be excreted
in the urine.Apart from this there is regular addition of more and
more new sodium and chlorine ions into descending limb by constant filtration. Thus, the
reabsorption of sodium chloride from ascending limb and addition of
new sodium chlorine ions into the filtrate increase or multiply the osmolarity of medullary
interstitial fluid and medullary gradient. Hence, it is called countercurrent multiplier.
Other Factors Responsible for Hyperosmolarity
of Medullary Interstitial Fluid
In addition to countercurrent multiplier action provided by the loop of Henle, two more
factors are involved in hyperosmolarity of medullary interstitial fluid.
i. Reabsorption of sodium from collecting duct
Reabsorption of sodium from medullary part of collecting duct into the medullary
interstitium, adds to the osmolarity of inner medulla.
ii. Recirculation of urea
Fifty percent of urea filtered in glomeruli is reabsorbed in proximal convoluted tubule.
Almost an equal amount of urea is secreted in the loop of Henle. So the fluid in distal
convoluted tubule has as much urea as amount filtered. Collecting duct is impermeable to
urea. However, due to the water reabsorption from distal convoluted tubule and collecting
duct in the presence of ADH, urea concentration increases in collecting duct. Now due to
concentration gradient, urea diffuses from inner medullary part of collecting duct into
medullary interstitium. Due to continuous diffusion, the concentration of urea increases in
the inner medulla resulting in hyperosmolarity of interstitium in inner medulla. Again, by
concentration gradient, urea enters the ascending limb. From here, it passes through distal
convoluted tubule and reaches the collecting duct. Urea enters the medullary interstitium
from collecting duct. By this way urea recirculates repeatedly and helps to maintain the
hyperosmolarity of inner medullary interstitium. Only a small amount of urea is excreted in
urine. Urea recirculation accounts for 50% of hyperosmolarity in inner medulla. Diffusion of
urea from collecting duct into medullary interstitium is carried out by urea transporters, UT-
A1 and UTA3, which are activated by ADH.
■COUNTERCURRENT EXCHANGER
Vasa Recta
Vasa recta functions as countercurrent exchanger. It is responsible for the maintenance of
medullary gradient, which is developed by countercurrent multiplier.