Question

1. Discuss the systems that regulate venous pressures.
2. What role does erythropoietin play in hematopoiesis of red blood cells and where is it made?
3. Why can plasma and volume expanders (such as albumin) be administered IV without fear of reactions – while blood cell products require a type and cross?

Answer 1

Atrial systole (0.1 sec) Atrial diastole (first part) 0.3 sec The events occurring repeatedly in the heart in a cyclical fashion constitute the cardiac cycle. If the heart rate is 75/min, 75 cardiac cjcles occur in 1 minute or 60 seconds. Therefore, the duration of one cardiac cycle = 60/75 = 0.8 sec. These events are—(a) Atrial and (b) ventricular. Each, again, can be divided into two main divisions-Systole (phase of contraction) and diastole (phase of relaxation). Protodiastole (0.04 sec) Isovolumetric relaxation phase (0.06 sec) First rapid filling phase (0.1 sec) Diastasis (0.2 sec) Second rapid filling phase (0.1 sec) Isovolumetric contraction phase (0.05 sec) Rapid ejection phase (0.11 sec) Slow ejection phase (0.14 sec) IATRIAL EVENTS Ventricular diastole Ventricular systole Fig. 30.1: Relation between atrial and ventricular events in cardiac cycle The atrial systole has a duration of 0.1 sec. This coincides with last (2nd) rapid filling phase of ventricular diastole (Fig. 30.1). Atrial diastole is long (duration is 0.7 sec). Atrial contraction helps in the pumping of only 30% of blood that enters the ventricles from the atria in ventricular diastole. The remaining 70% of diastolic inflow into ventricles from atria is passive and does not require atrial contraction. Hence, in atrial fibrillation, where there is no effective atrial contraction, there is no active flow of blood from atria to į ventricles during atrial systole. Still, the Patient survives as ventricular filling is maintained by the passive flow of blood from atria. [Atrial fibrillation is a condition where the atrial muscles contract in a totally uncoordinated fashion like a "bag of worms'. Due to this ineffective atrial contraction in atrial systole, active atrial output (amount of blood ejected by atrial contraction) is almost nill

waves. veins in the neck are engorged and the upper ends of venous waves are visible at a higher level than normal. This is an important, easily demonstrable sign of congestive heart failure. Fig. 30.4: Jugular venous waves (see text) In complete heart block, atrial and ventricular contractions occur indepen- These are known as jugular venous dently. Sometimes, atria and ventricles contract Where are 3 upward waves a, c and v. simultaneously. In this situation, atrial so there are 2 downward waves x and y. systole takes place against closed tricuspid The upward waves obviously indicate rise valves. The intraatrial pressure rises in intraatrial pressure whereas downward tremendously and atrial blood backflows waves indicate fall in intraatrial pressure. sharply into jugular veins. This produces Now, what is known as cannon wave. a wave Caused by atrial systole. 'a' wave is absent in atrial fibrillation c wave → Caused during isovolume- because there is no effective atrial tric contraction phase due contraction in this condition. to bulging of a-v valves Central venous pressure: It is the into the atria. Intraatrial pressure of blood in the great veins which volume is reduced and drain into right atrium. So, it equals intraatrial pressure rises. right atrial pressure. It is a measure of x descent → Caused during ejection venous return and determines preload by phase when there is influencing EDV. ventricular shortening. More the CVP (central venous pressure), The a-v valve rings are less is the venous return (due to back pulled downward. This pressure of CVP). leads to atrial dilatation However, one should note that less the and pressure-drop inside venous return, less is the CVP. atria. CVP depends on: v wave → Caused by accumulation a. Venous return of blood in atria before b. Cardiac pumping (cardiac pumping opening of a-v valves. empties atria and great veins. So, y descent + Caused as atrial pressure CVP is reduced). drops due to flow of blood c. Intrathoracic pressure-Greater in- from atria to the ventricles trathoracic pressure increases CVP. during first rapid filling FACTORS CONTROLLING VENOUS hese venous waves are recorded by RETURN (FIG. 30.5] congestive (right-sided) heart failure 1. Cardiac Suction-Cardiac pumping 1), the jugular venous pressure is high increases venous return by suction effect 0 back-pressure. As a result, jugular as follows: Scanned with .. ConScanner phase. Mckenzie's polygraph. (p.351), the jugy due to back-pl

icular diastole blood agair rentricles front st or 2nd rapia heart sound e to onrush of the ventricles. Note: The third heart sound is produced a little later than the opening of the atrioventricular valves. This is because, in the initial part of 1st rapid filling phase, the ventricular wall is flaccid and inelastic. Only after some amount of blood enters into the ventricle and makes the ventricular wall taut and elastic that further flow of blood from atria to ventricles can produce the third heart sound. 12. When the pressure gradient between atria and ventricles is reduced after the initial rapid flow, blood flow becomes very slow. This is the period of diastasis. When tachycardia causes diastolic shorte- ning, this phase of diastole is shortened most. 13. In the last part of ventricular di atrial systole begins and blood flows rapidly into the ventricles the atria. This is the last or 2nd filling phase. The fourth heart occurs at this stage due to onru blood from the atria to the ventri The end of the last rapid filling phace marks the end of diastole and a cardiac cycle begins. Events in the right ventricle are similar to those in the left ventricle except that the pressure of blood in right ventricle operates at a much lower level Jugular venous waves: [Fig. 30.4] The changes in right atrial pressure cause waves in internal jugular vein by back- pressure. Ventricular systole Ventricular diastole Atrial systole Atrial systole Ventricular volume a → Closure of atrioventricular valve causing S, b→ Opening of atrioventricular valve with end of isovolumetric relaxation Scanned with CamScanner Fig. 30.3: Changes in ventricular volume during cardiac cycle

e becomes fixed. So, this phase ntraction is called isovolumetric end of systole, ventricle become of contraction diastole 3. Previous) contraction 4. Strong 7. At the (ventricular relaxation) begins. Initially contraction phase. the intraventricular pressure is lower Previously, this was called isometric than the aortic pressure. In spite of this, contraction phase. But strictly the semilunar (aortic) valve fails to close peaking, this is incorrect since small as blood continues to flow from the changes in length occur in some muscle ventricle into the aorta due to inertia. fibers during this phase. This phase is called protodiastole. ng contraction of ventricular 8. Ultimately, the force of inertia wanes. Iscle exerted on the blood confined Now, the direction of blood flow is within the closed ventricular cavity reversed and blood now flows from results in sharp rise of intraventricular a higher pressure in the aorta to a ssure. (Note that blood is incompre- lower pressure in the ventricle. As a result, the aortic valve, which prevents ssible). When this pressure exceeds the flow of blood from aorta to ventricle, aortic pressure (80 mmHg), the aortic closes. This produces the second heart valve opens. Now, blood begins to sound (S) which marks the end of flow into the aorta at a high velocity. protodiastole. This marks the beginning of the rapid When the aortic valve closes, blood ejection phase. flowing back from aorta to left ventricle 5. With continued ventricular contrac is obstructed and reflected back from tion, both intraventricular and the closed aortic valve. This creates intraaortic pressure rise, to usually a notch in the aortic pressure curve, a peak of 120 mmHg in this rapid known as dicrotic notch. ejection phase. The intraaortic pressure 9. Clinical systole is the period between rises because blood enters the aorta at S, and S, and includes protodiastole besides true systole. a greater rate than the run-off of blood 10. When the aortic valve closes, the from the aorta to the periphery. ventricle once again becomes a 6. After some blood is ejected from the closed chamber. The ventricle now ventricle, intraventricular pressure undergoes isovolumetric relaxation. begins to drop in the later part of systole. The intraventricular pressure falls As a result, ejection becomes reduced. rapidly and ultimately becomes lower This is the reduced ejection phase. The than the atrial pressure. At this point, intraaortic pressure also drops as the the atrioventricular valves open. run-off of blood to periphery now This marks the end of isovolumetric exceeds the amount of blood coming relaxation phase and beginning of first rapid filling phase. In the last part of ejection phase, 11. In the first rapid filling phase, blood rapidly flows into the relaxed ventricle traventricular pressure becomes lower than intraaortic pressure from the atria. The third heart sound od flows from the ventricle into the is produced due to the rapid flow of corta due to inertia. (Also see below) blood into the ventricle. into the aorta. intraaortic pressure. Still, CamScanner

However, one must note that atrial contraction plays a vitally important #role during exercise. During exercise, the heart rate is very high and this shortens the diastole considerably. It is the active atrial contraction, acting as a booster pump, that improves ventricular filling to a satisfactory extent during the shortened diastole. Diastole 1. Protodiastole-0.04 sec 2. Isovolumetric relaxation phase-0.06 ser 3. First rapid filling phase—0.1 sec 4. Diastasis-0.2 sec 5. Last (2nd) rapid filling phase-0.1 ser VENTRICULAR EVENTS (FIGS 30.2 AND 30.3) The ventricular systole has a duration of 0.3 sec while ventricular diastole extends for 0.5 sec. These stages are further divided into: Systole 1. Isovolumetric contraction phase-0.05 sec. 2. Rapid ejection phase-0.11 sec. 3. Slow ejection phase—0.14 sec. Description of events in left ventricle 1. As diastole ends, the ventricle is filled with blood. Now, the ventricle starts contracting, commencing a new systole. The intraventricular pressure tends to rise and blood tends to backflow into the atria. At this point, the atrioventricular valves, which prevent backflow of blood from ventricles to atria, close producing the first heart sound (S.). 2. With this, the ventricle becomes a closed cavity and the volume of the Slow ejection phase Rapid ejection phase Isovolumetric contraction phase Last rapid filling phase VIII, Protodiastole Isovolumetric relaxation phase First rapid filling phase -Diastasis il lil Mý ví vil Aortic pressure curve - Venous pressure curve - Left ventricular pressure curve Scanná CamScanner ECG tracing Fig. 30.2: Changes in aortic pressure, left intraventricular pressure, venous pressure and ECG Waves during cardiac cycle

Erythropoietin, shown here complexed with the extracellular domains of its two receptor molecules (EPObp 1 and EPObp2), is the "incredible hulk" of hormone- receptor complexes. . Erythropoietin (EPO) resembles a classic endocrine hormone in that it exerts its effect on target cells in bone marrow through interactions with specific cell-surface receptors. The role of erythropoietin is to control red blood cell production by regulating the differentiation and proliferation of erythroid progenitor cells in the bone marrow. Produced primarily in the kidney, erythropoietin circulates in the plasma and acts on target cells in the bone marrow.

98 Principles of Physiology monocytes and platelets. Mach sinuses can des Yellow bor Pluripotent stem cell c. Distribution and yellow be mentioned ab 7. However, in cases yellow bone m into red bone m hemopoiesis in occur under thes Proerythroblast Early normoblast Intermediate normoblast Pyknotic nucleus Late normoblast STEPS OF ERYTH 1. The pluripoten primitive cell formed. So, it precursor of al 2. The pluripote to committed the precursors Committed ste a. Committed b. Committed The comm give rise to cells called CE ultimately give to granulocyt lets. 3. CFU-GEMM RBCs, first g unit for ery and then thes colony formi (CFU-E) celle 4. CFU-E cells erythropoieti their growth 5. Pronormobla a. The CFU pronorm Extruded nucleus Reticulocyte Mature RBC Fig. 12.3: Steps of erythropoiesis whereas yellow bone marrow con- tains fat cells, reticulum cells, blood vessels and fibers. b. Red bone marrow is active and forms RBCs, granulocytes, some amount of

Erythropoietin activates target erythroid colony-forming cells by binding and orienting two cell surface erythropoietin receptors. The orientation of the EPO receptors is critical for efficient signalling. Proper binding triggers an intracellular phosphorylation cascade, which activates both the Ras/MAP kinase pathway and the STAT (signal transducer and activator of transcription) pathway. These pathways play a major role in cytokine-induced signalling and are involved in increased cell proliferation in response to EPO. Erythropoeitin participates in a classic feedback control system, as production of erythropoietin is regulated by impaired oxygen delivery to the kidney. Hypoxia causes an increase in erythropoietin gene transcription, enhancing red blood cell production.

Synthetic erythropoietin (Epoetin) is prescribed for the treatment of anemia, especially for individuals with cancer, AIDS, or kidney problems. However, because it stimulates the production of red blood cells, EPO hormone is also used illegally by athletes to increase their aerobic capacity and muscle endurance, making it worthy of the title "incredible hulk".

EPO is secreted from the tubuler cells of the real cortex.

2.
The composition of plasma reflects that of the extravascular extracellular space, the milieu intrieur of Claude Bernard, with some important differences. Indeed it also contains hormones, nutrients, and end-products of metabolism transiting through the circulation; it contains clotting factors, components of the inflammatory and fibrinolytic pathways in various stages of activation, and immunoglobulins. All this component are same in each human body and doesn't include any antigen Or antibody. So they are administered without fear of reaction.

: on the other hand When blood products are ordered to be administered to a patient who requires transfusion, a series of tests are performed to decrease the risk of an immune-mediated hemolytic reaction caused by incompatible blood.

Hemolytic transfusion reactions occur when the recipient's immune system encounters antigens from donor blood. Antibodies may form in response to these antigens, resulting in destruction of donor red blood cells (RBC: The type and screen are the first pretransfusion compatibility tests performed, and they are used to identify the patient's ABO group and Rh type as well as to detect expected and unexpected antibodies in the patient's serum, respectively.
The crossmatch is the final step of pretransfusion testing as a routine procedure. A portion of donor blood is combined with patient plasma or serum and is checked for agglutination, which would signify incompatible blood. This important step, also known as major crossmatch, serves as the last guard to ensure a safe transfusion

: It's important for donor blood to match your own as closely as possible. Otherwise, your immune system might create antibodies against the donor blood cells. In this case, your immune system correctly views the donor cells as foreign, but incorrectly views them harmful. This can lead to a dangerous and possibly fatal reaction