Compilation Cardiac Bio-1

SUBJECT: EMBRYOLOGYNAMA: AZLINDA HAIZA HANAPI3. Describe the right atrium of the heart. Add a brief notes on its development

-Forms the right border of the heart between superior and inferior venae cavae-Receive venous blood from these large vessels and coronary sinus-The coronary sinus lying in the posterior part of coronary groove, receive blood from the veins of the heart and open to RA-The internal wall of the RA consist of

A smooth posterior part – sinus venarum whish receive the venae cava and coronary sinus

A rough anterior part – internal muscular ridge-The R auricle – is a small, conical muscle pouch tat project to the L from the RA and overlaps the ascending aorta-The 2 distinct parts of the RA are separated

Externally – sulcus terminalis (a shallow vertical groove on the posterior aspect of RA)

Internally- crista terminalis(a vertical ridge)-Sinus venarum originates from the right horn of the sinus venoses-The embryonic RA becomes the trabeculated right atrial appendage containing the pectinate muscle

Inferior part of RA : Three openings present (into the atrium) – coronary sinus, IVC opening at the 5 TH

costal cartilage (around the apex) and SVC opening in its superior part. Also an AV orifice where the deoxygenated blood pass to ventricles.

Sulcus terminalis – external / terminal grooveCrista terminalis- internal / terminal crestBoth separates the primordial atrium and sinus venarum.

SUBJECT: ANATOMYNAMA:

1)Anatomy of coronary arteryA)Right (R) coronary artery-arises from R aortic sinus-gives off SINUATRIAL NODAL BRANCH-passes btwn R auricular appendage and infundibulum of R ventricle (where pulmonary artery emerges)-passes vertically down in AV groove and then runs posteriorly-supplies R atrium and ventricle-at inferior border:RIGHT MARGINAL BRANCH-at crux of heart-gives AV NODAL BRANCH-on diaphragmatic surface-POSTERIOR INTERVENTRICULAR BRANCH/INFERIOR IV BRANCH)Gives INTERVENTRICULAR SEPTAL BRANCHES-passes to apex-anastomoses by terminal arterioles with termination of L coronary artery at lower part of L atrium

B)Left (L) coronary artery-arises from L aortic sinus-emerges from btwn L auricular appendage and infundibulum of L ventricle-passes backward along AV groove-near upper border of heart,gives off ANTERIOR INTERVENTRICULAR BRANCH-then passes to apex-ANTERIOR INTERVENTRICULAR ARTERY may give a LATERAL (DIAGONAL) BRANCH-parent trunk then named CIRCUMFLEX ARTERY, which passes down in posterior AV Groove-gives LEFT MARGINAL BRANCH and anastomoses with R coronary artery below coronary sinus

2)arterial blood supply of pacemaker of the heart is actually blood supply of SINUATRIAL NODE which is from LEFT CORONARY ARTERY

3)Why myocardial infarction is associated with AV conduction block? -normally,the action potential initiated in SA node are conducted to entire myocardium through specific conducting cells such as AV node -from AV node the action potential is pass to bundle of His, then Purkinje system -but in myocardial infarction the action potential initiated by SA node can not be con- ducted to coronary muscle since the muscle has infarct (die) -so there is also no conduction of action potential to AV node from SA node**-myocardial infarction occurs when supply of blood to coronary muscle is reduced below critical value, so restricting supply of vital nutrients and oxygen to coronary muscle. -this then cause muscle to infarct (die)

4 AV block on ECG

1st degree of AV block-simple prolongation of PR interval to more than 0.22 seconds-every atrial depolarization is followed by conduction to the ventricle but with delay2nd degree of AV block-some P waves conduct and others do not

3rd degree of AV block (complete)-occur when all atrial activity fails to conduct to ventricles

SUBJECT: ANATOMYNAMA: AMALIA MARDHIAH ZALALUDIN

Question :Left coronary arteries (+ its branches)Answer :

The left coronary artery (LCA) arises from the left aortic sinus of the ascending aorta. It passes between the left auricle and pulmonary trunk in the coronary groove. At the left end of the coronary grove, the LCA divides into two branches, an anterior interventricular branch (left anterior descending branch, LAD branch) and a circumflex branch.

The LAD branch passes along the interventricular groove to the apex of the heart, where it turns around the inferior border of the heart and anastomoses with the posterior interventricular branch of the right coronary artery (RCA). The LAD branch supplies both ventricles and the interventricular septum. Usually the LAD branch gives rise to a lateral (diagonal) branch, which descends on the anterior surface of the heart.

The smaller circumflex branch of the LCA follows the coronary groove around the left border of the heart to the posterior surface of the heart. The left marginal artery, a branch of the circumflex branch, follows the left margin of the heart and supplies the left ventricle. The circumflex branch terminates on the posterior aspect of the heart and often anastomoses with the posterior interventricular branch of the RCA.

SUBJECT: ANATOMYNAMA: AMALIA MARDHIAH ZALALUDIN

Question :Left ventricle

Answer :The left ventricle (LV) forms the apex of the heart, nearly all its left (pulmonary) surface and

border, and most of the diaphragmatic surface. It performs more work than the right ventricle (RV) because arterial pressure is much higher in the systemic than in the pulmonary circulation, therefore its walls are twice as thick as that of RV. The interior walls of the LV are also mostly covered with a mesh of trabeculae carneae that is finer and more numerous than that of the RV.

The interior of the LV has a double-leaflet mitral valve that guards the left atrioventricular orifice. The conical cavity of the LV is longer than that of the RV and it has anterior and posterior papillary muscles that are larger than those in the RV.

A superoanterior outflow part is formed by the smooth-walled aortic vestibule leading to the aortis orifice, which lies in its right posterosuperior part. The aortic orifice is surrounded by a fibrous ring to which the right, posterior, and left cusps of the aortic valve are attached.

SUBJECT: PHYSIOLOGYNAMA: SITI AFIFAH ABD MANAS

QUESTIONS: DESCRIPTION OF RIGHT VENTRICLE OF THE HEART 

ANSWERS: Normal human heart has four chambers to regulate the blood circulation in our body. The

chambers are right atria, right ventricle, left atria and left ventricle. The right chambers regulate blood from the body to the lung for oxygenation where the oxygen will diffuse into the red blood cell and the carbon dioxide will be diffused out from the red blood cell down the concentration. Whereas the left chambers will regulate blood from the lung to the whole systems of our body. Therefore these chambers have formed the parallel circulation to ensure that the blood is circulated throughout the body.

The poor oxygenated blood is brought to the right heart from body via superior vena cava (SVC) and inferior vena cava ( IVC). Then the blood passes through right atria and right ventricle before being pumped to the lung through pulmonary trunk.

Right ventricle is separated by atriventricular groove from the right atria and separated by interventricular groove from the left ventricle. Right ventricle forms the anterior (sternocostal) and inferior (diaphragmatic) surfaces of the heart.

Right ventricle of heart is crescentic-shaped in cross section and superiorly tapers into infundibulum or conus arteriosus which will lead to pulmonary trunk. It has a sponge-liked wall which is composed by trabeculae carnae. The wall of right ventricle is thicker than the right atria due to higher pressure that needed to pump the blood to the lung. However the wall of left ventricle is three times thicker than that of right ventricle because it has to pump the oxygenated blood throughout the body systems.

The blood that passes from right atria to right ventricle is regulated by the tricuspid valve which has three cusps, the anterior, septal and inferior cusps. The tricuspid valve is connected to the papillary muscle by the chordae tendinae to prevent inversion of the cusps. Hence the blood would not flow backward into the right atria and the vena cava. Rupture of the papillary muscle will lead to incompetence in of the tricuspid valve. Pulmonary valve regulates the blood that passes from right ventricle to pulmonary trunk. It is consists of three semilunar cusps which are the anterior, right, and left cusps. They are composed of endocardium and connective tissue and their role is to guard the pulmonary orifice.

The contraction of right ventricle or known as systole phase and the relaxation of the right ventricle or diastole phase are controlled by the electrical signal. This signal is initiated in sino –atrial node (SAN) which is at the right atria, and conducted to right ventricle through atrioventricular node (AVN). During relaxation the right ventricle will be filled with the non oxygenated blood and during contraction, the right ventricle will pump the blood to the lung to be oxygenated.

SUBJECT: ANATOMYNAMA: ANIP HUSMANDescribe the right ventricle of the heart 

Right ventricle of heart is ½ thick to the left ventricle. It forms most of the anterior surface and part of the diaphragmatic (inferior) surface of the heart.It is also occupying most of the inferior border of heart (Remember: heart has 4 borders, 3 surfaces, 1 base and 1 apex). In right ventricle, there is a rough surface called Trabaculae carnae that occupy most of right ventricle internal surface and also smooth surface that ascend towards the pulmonary orifices called Conus anteriosus / Infundubulum. There is also Interventricular (I.V) septum (Muscular-inferior, Membranous-superior) that runs between right ventricle and left ventricle. In conducting myocardium, Bundle of His will be occupying the I.V septum and give branch to right ventricle Purkinje Fibers and also septomarginal trabaculae in right ventricle area. This highly specialized myocardium only involves in conduction of impulse in heart and does not involve in heart contraction. Ventricular Septal Defect (VSD) is a congenital defect that result an ostium (hole) in I.V membranous septum. This would result a mix of blood from left ventricle and right ventricle. Heart response to this condition is by hypertrophy of heart...There is another septum that runs between right atrium and right ventricle called atrioventricular septum with tricuspid valve located in this septum.

Right heart receives deoxygenated blood from right atrium. The movement of blood from right atrium is control by the tricuspid valve. Tricuspid valve has 3 cusps and its movement are control by papillary muscle, a rough muscle underneath the valve from trabaculae carnae and its branch, cordae tendinae that attach to each cusp of tricuspid valve. If pressure in right atrium is larger than right ventricle, tricuspid valve will be open with cordae tendinae will tend to pull tricuspid valve cups so that blood flow can run from right atrium to right ventricle and vice versa. Superior to infundubulum, there is pulmonary orifices. Pulmonary valve with 3 cusps located at pulmonary orifices. Deoxygenated blood from systole of right ventricle will pass through pulmonary valve to pulmonary artery and enter the lung (Pulmonary arterial circulation) for gases exchange.

Dah habis lar …Gud luck 4 ur exam.

SUBJECT: ANATOMYNAMA: EILEEN FARHANA BINTI SHAIR

Give an account of the coronary circulation.Coronary circulation is the artery, vein and the lymph supply to the heart.

ARTERY

The arterial supply of the heart is provided by the right and left coronary arteries, which arise from the ascending aorta (first branch of the aorta- supplying the myocardium and epicardium of the heart). The coronary arteries and their major branches lie within the subepicardial connective tissue.

The right coronary artery arises from the anterior aortic sinus of the ascending aorta (superior to aortic valve). It runs forward between the pulmonary trunk and the right auricle. It descends in the right atrioventricular groove. At the inferior border of the heart, it continues posteriorly along the atrioventricular groove to anastamose with the left coronary artery in the posterior interventricular groove.

Branches of from the right coronary artery supply the right atrium, right ventricle and parts of the left atrium and left ventricle and the atrioventricular septum.

1. right conus artery supplies the anterior surface of the pulmonary conus (infundibulum of the right ventricle) and the upper part of the anterior wall of the right ventricle.

2. anterior ventricular branches supply the anterior surface of the right ventricle. The right marginal branch is the largest and runs along the lower margin of the costal surface to reach the apex.

3. posterior ventricular branches supply the diaphragmatic surface of the right ventricle.4. posterior interventricular (descending) artery runs toward the apex in the posterior

interventricular groove. It gives off branches to the right and the left ventricles, including its inferior wall. It supplies branches to the posterior part of the ventricular septum but not to the apical part

a. The apical part receives its supply from the anterior interventricular branch of the left coronary artery. A large septal branch (AV nodal branch from RCA) supplies the atrioventricular node.

b. In 10% of the individuals the posterior interventricular artery is replaced by a branch from the left coronary artery.

5. atrial branches supply the anterior and lateral surfaces of the right atrium. One branch supplies the posterior surface of both the right and left atria. The artery of the sinoatrial node (sinoatrial nodal branch) supplies the node and the right and left atria.

a. in 35% of individuals it arises from the left coronary artery.

The left coronary artery is usually larger than the right coronary artery. It supplies the major part of the heart, including the greater part of the left atrium, left ventricle and the ventricular septum. It arises from the left posterior aortic sinus of the ascending aorta and passes forward between the pulmonary trunk and the left auricle. It then enters the atrioventricular groove and divides into an anterior interventricular branch and a circumflex branch.

1. the anterior interventricular (descending) branch runs downward in the anterior interventricular groove to the apex of the heart. It supplies the right and the left ventricles with numerous branches that also supply the anterior part of the ventricular septum. Left diagonal artery may arise directly from the trunk of the left coronary artery. A small left conus artery

supplies the pulmonary conus. In most individuals, the descending branch then passes around the apex of the heart to enter the posterior interventriculalr groove and anastamoses with the terminal branches of the right coronary artery.

a. In 1/3 of the individuals, it ends at the apex of the heart. 2. the circumflex artery is the same size as the anterior interventricular artery. It winds around

the left margin of the heart in the atrioventricular groove. A left marginal artery is a large branch that supplies the left margin of the left ventricle down to the apex. Anterior ventricular and posterior ventricular branches supply the left ventricle. Atrial branches supply the left atrium

VEIN

Most blood from the heart wall drains into the right atrium through the coronary sinus, which lies in the posterior part of the atrioventricular groove and is a continuation of the great cardiac vein. The small and middle cardiac veins are tributaries of the coronary sinus. The remainder of the blood is returned to the right atrium by the anterior cardiac vein and by small veins that open directly into the heart chambers.

The coronary sinus receives the anterior interventricular vein (aka great cardiac vein) at its left and the posterior intervnetricular (aka middle cardiac vein) and cardiac vein at its right. Other venous drainage of the heart are oblique vein of the left atrium, anterior cardiac veins and the smallest cardiac veins (valveless).

Great cardiac vein : accompanies first anterior interventricular artery, then circumflex arterydrains are supplied by left coronary arteryjoined by the upper two large posterior left ventricular veins

the middle and small cardiac veins drain area of distribution of the RCA

Middle cardiac vein :Accompanies posterior interventricular artery (part of right coronary artery territory)

Small cardiac vein:May drain into right atrium directlyAccompanies right marginal arteryCan be considered the lowest and largest anterior cardiac vein

Anterior cardiac veins :Cross anterior surface of right ventricleUsually drain directly into right atriumDrain most the of the remaining 40% blood

Venae cordis minimae :Drain directly into all four chambersValveless – form antrioventricular shunts / collateral circulation fo parts of myocardium

LYMPHATIC DRAINAGE

Lymphatic vessels in the myocardium and subendothelial connective tissue pass to the subepicardial lymphatic plexus. Vessels from this plexus pass to the coronary groove and follow the coronary arteries. A single lymphatic vessel, formed by the union of various vessels from the heart, ascends between the pulmonary trunk and left atrium and ends in the inferior tracheobronchial lymph nodes, usually on the right side.

References1. clinical anatomy for medical students by SNELL (page 101-105)2. clinically oriented anatomyby MOORE (mama moore) page 1333. lecture notes by Dr.J Thompson 11 January 2005 (The Heart 2)

SUBJECT: ANATOMYPENAIP: FARAH KHALIDA

Write an essay on the thoracic part of the oesophagus In superior mediastinum

The esophagus is a fibromuscular tube that extents from pharynx to the stomach It usually flattened anteropasteriorly The esophagus enters the superior mediastinum between the trachea and vertebral column,

where it lies anterior to the bodies of vertebrae T1 through T4 Initially, the esophagus inclines to the left but is moved by the aortic arch to the median plane

opposite the root of the lug The thoracic duct usually lies on the left side of the esophagus and deep to the aortic arch Inferior to the arch, the esophagus inclines to the left as it approach and passes through the

esophangeal hiatus in the diaphragm

Posterior mediastinum

The esophagus descends into the posterior mediastinum from the superior mediastinum, passing posterior and to the right of the aorta and posterior to the pericardium and left atrium

The esophagus constitutes the primary posterior relationship of the base of the heart If then deviation to the left and passes through the esophangeal hiatus in the diaphragm at the

level of T10 vertebra, anterior to the aorta The esophagus is compressed by

The aortic arch Left main bronchus Diaphragm

No constriction are visible in the empty esophagus As it expands during filling, the above structures compress its walls

Nerves, artery and vein

Esophangeal arteries supply the middle third of the esophagus Then blood move into esophangeal vein Azygos vein receive esophangeal vein

Usually the right vagus nerves leaves the pulmonary plexus as a single nerve and passes to the esophagus, where it again breaks up and contributes fibres to the esophageal plexus-supply nerves to esophagus

Left vagus-join right vagus to form esophangeal plexus

SUBJECT: ANATOMYNAMA: Fifa

QUESTION: Draw a normal electrocardiogram and discuss the electrical event in the heart underlying each of the ECG waves. How would you measure the PR interval, QRS duration and the QT interval, and what are their normal ranges, and in what abnormality of the conducting system might they be abnormal?

normal ecg wave.

P wave happens due to depolarisation of atrial. Wheraeas QRS complex represents ventricular depolarisation. The event of repolarization cannot be seen because it is buried in the QRS complex. On the other hand, the T wave is representing the repolarization of ventricles. There is a plateau phase or known as ST segment starting from the end of the ventricular depolarisation event to the initial repolarization of ventricles.

We can count the PR interval, QRS duration and the QT interval by counting the number of small boxes within the interval and multiply it with

PR interval is the time between the onset of the P wave and the onset of the QRS complex. Normally its normal range is between 0.12 to 0.2 seconds.

QRS duration consists of waves of Q, R, and S which represents depolarisation of ventricles. Its normal range is between 0.08 to 0.10 seconds.

QT interval is the time between the onset of the QRS complex and the end the end of the T wave. Its normal range is between 0.33 to 0.43 seconds.

Some abnormalities in heart can be detected from the abnormalities in ecg wave. Usually abnormally long in PR interval is due to delay in AVN or heart block. This happens because the AVN fails to transmit the action potential from the atria to the ventricle.

If the PR interval is abnormally short, it might be due to arrythmias. The myocardial cells are excitable earlier and often.

If the QRS complex is longer, it might be due to the slower conduction velocity in His-Purkinje system.

If the deflection of G is too large, heart attack might be happened. Whereas if the QRS complex is abnormally large, it means that there is a large different of action potential.

If the QT interval is prolonged, it might be related to the problem with repolarization of ventricular muscle cells such as hyperthermia and congenital defect.

SUBJECT: PHYSIOLOGYNAMA: HAFIZ ALI

Describe the conduction of electrical signal through the chamber of the heart. How is he heart block produce?

Intro 1) Heart consists of four chambers which are left atrium, left ventricle, right atrium and right

ventricle.2) The conduction system coordinates the cardiac cycle.3) The heart consists of two kinds of muscles cells:

-contractile cells Comprise the majority of atrial and ventricular tissues and are the working cell of the

heart. Action potential in contractile cells leads to contraction and generation of force and

pressure-conducting cells

Comprise of the tissue of SA node, the atrial internodal tracts, the AV node, the bundle of His, and the Purkinje system.

Conducting cells are specialized cells that do not contract and generate force, instead they function to rapidly spread action potential over the entire myocardium.

Another feature of the specialized conducting tissues is their capacity to generate action potential spontaneously.

Content1) SA node

-normally, the action potential of the heart is initiated in the specialized tissue of the SA node, which serves as the pacemaker.-after the action potential is initiated in the SA node, there is a very specific timing and sequence for the conduction of action potential to the rest of the heart

2) Atrial internodal tracts and atria-the action potential spread from the SA node to the right and left atria via the atrial internodal tracts.-simultaneously the action potential is conducted to the AV node

3) AV node-conduction velocity through the AV node is considerably slower than in the other cardiac tissue.-slow conduction through the AV node ensures that the ventricles have enough time to fill with blood before they are activated and contract.Increases in conduction velocity of the AV node can lead to decreased ventricular filling and decreased stroke volume and cardiac output.

4) Bundle of His, Purkinje system, ventricles-from the AV node, the action potential enters the specialized conducting system of the ventricles.-the action potential is first conducted to the bundle of His through the common bundle.-if then invades the left and right bundle branches and the Purkinje system.-conduction through the His-Purkinje system is extremely fast, and it rapidly distributes the action potential to the ventricles.-the action potential also spread from one ventricular muscle to the next, via low resistance-pathways between the cells(gap junction)-rapid conduction essential and allow for efficient contraction and ejection of the blood.

Heart block

1) Heart block is a disruption in the relay of electrical signals that control activity of the heart muscle.

2) Sometimes the signal from the heart's upper to lower chambers is impaired or doesn't transmit. This is "heart block" or "AV block." This does not mean that the blood flow or blood vessels are blocked.

3) Heart block is classified according to the level of impairment -- first-degree heart block, second-degree heart block or third-degree (complete) heart block.

First degree heart block

First-degree heart block, or first-degree AV block, is when the electrical impulse moves through the AV node more slowly than normal. The time it takes for the impulse to get from the atria to the ventricles (the PR interval) should be less than about 0.2 seconds. If it takes longer than this, it's called first-degree heart block.Heart rate and rhythm are normal, and there may be nothing wrong with the heart.Certain heart medicines such as digitalis can slow conduction of the impulse from the atria to the ventricles and cause first-degree AV block. Also, well-trained athletes may have it.Generally, no treatment is necessary for first-degree heart block.

Second degree heart block

In this condition, some signals from the atria don't reach the ventricles. This causes "dropped beats." On an electrocardiogram, the P wave isn't followed by the QRS wave, because the ventricles weren't activated. There are two types:

-Type I second-degree heart block, or Molitz Type I, or Wenckebach's AV block. Electrical impulses are delayed more and more with each heartbeat until a beat is skipped. This condition is not too serious but sometimes causes dizziness and/or other symptoms.

-Type II second-degree heart block, or Molitz Type II. This is less common than Type I but generally more serious. Because electrical impulses can't reach the ventricles, an abnormally slow heartbeat may result. In some cases a pacemaker is needed.

Third degree heart block

Complete heart block (complete AV block) means that the heart's electrical signal doesn't pass from the upper to the lower chambers. When this occurs, an independent pacemaker in the lower chambers takes over. The ventricles can contract and pump blood, but at a slower rate than that of the atrial pacemaker.

These impulses are called functional or ventricular scope beats. They're usually are very slow and can't generate the signals needed to maintain full functioning of the heart muscle. On the electrocardiogram, there's no normal relationship between the P and the QRS waves.

Complete heart block is most often caused in adults by heart disease or as a side effect of drug toxicity. Heart block also can be present at -- or even before -- birth. (This is called congenital heart block.) It also may result from an injury to the electrical conduction system during heart surgery. Complete heart block may be a medical emergency with potentially severe symptoms and a serious risk of cardiac arrest (sudden cardiac death). If a pacemaker can't be implanted immediately, a temporary pacemaker might be used to keep the heart pumping until surgery can be performed.

SUBJECT: ANATOMYNAMA: HALY ROZI

17.Describe the physiological compensation for acute moderate hypovolaemia due to hemorrhage. What symptoms and signs would you expect in a previously normal individual who acutely losses 20% of their blood volume?

The initiating event in hemorrhage is loss of blood and decrease in blood volume.This will give rise to decrease in arterial blood pressureWhen blood volume decreases, mean systemic pressure decreases and the vascular function curve shift to the left. In the new steady state, the cardiac and vascular function curve intersect at a new equilibrium point where both cardiac output and right arterial pressure are decreased.(refer to effect of hemorrhage in mean arterial pressure-graph)

The reduction in blood volume causes a decrease in venous return and decrease in right atrial pressure. When venous return reduced, there’ll be a corresponding decrease in cardiac output. Decrease in cardiac output will lead to a decrease Pa, since Pa is the product of cardiac output and TPR .Hence, cardiac output and Pa decrease almost immediately, but so far there’s no change in TPR (this will change later in the compensatory response)

1) responses of the baroreceptor reflex

baroreceptor in the carotid sinus detect the decrease in Pa and relay the information to the medulla via the carotid sinus nerve. The medulla coordinates an output that is intended to increase Pa back to normal. Sympathetic outflow to the heart and blood vessel increases, and parasympathetic outflow to the heart decreases. the 4 consequences of the autonomic reflexes area) increased heart rate-results in increase of cardiac outputb) increased contractility-results in increase cardiac outputc) increased TPR-(due to arteriolar vasoconstriction in many vascular beds)-results in more blood being held on the arterial side-increase stress volumed) constriction of the veins-which reduces unstressed volume increase venous return and increased stressed volume-results in decrease compliance and capacitance –increase venous return and cardiac output

All responses are to increase Pa

2)responses of the Renin –Angiostensin II-Aldosterone System

When Pa decreases,renal perfusion pressure decreases which stimulates the secretion of rennin from the juxtaglomerular cell. Renin in turn increases production of angiostensin I which then converted to angiostensin II.Action of angiostensin II

1) causes arteriolar vasoconstriction, reinforcing and adding to increase in TPR from the increased sympathetic outflow to the blood vessels.

2) Stimulate secretion of aldosterone which circulates the kidney and causes increased in reabsorption of Na+ which will increase ECF volume thereby raising blood volume and reinforcing the increase in stressed volume, which resulted from a shift of blood from the veins to the arteries

3)responses in the capillariesThe response include the Starling forces across capillary walls.these compensatory changes favour absorption of fluid into capillaries as follows

Increase sympathetic outflow to blood vessel and increased angiostensinII both produce arteriolar vasoconstriction. As a result, there’s a decrease in capillary hydrostatic pressure Pc which opposes filtration out of the capillary and favours absorption

3) response to Antidiuretic hormone

Antidiuretic hormone is secreted in response to decrease in blood volume,mediated by volume in right atria.ADH has 2 actions:

a)increase water reabsorption by renal collecting ducts which help to restore blood volumeb)causes arteriolar vasoconstriction effects of sympathetic activity and angiostensin II

symptoms and signs:

decrease blood Padecrease pulse pressuredecrease in heart ratedecrease in urine productioncool,pale skin

SUBJECT: ANATOMYNAMA:

Define preload, contractility and afterload and discuss their influence on stroke volume and cardiac output. Briefly account for the effects of hypertension on the heart.

Preload is the ventriclular volume at the end of diastole or end-diastolic volume while afterload is the resistance to ventricular ejection Contractility is the performance of the heart at a given preload and afterload. Stroke volume is volume of blood ejected from the ventricles per beat It is determined by three factors that is preload, afterload, and contractility An increased preload leads to an increased stroke volume Preload depend mainly on the return of venous blood from the body There is a relationship between the stroke volume and the end-diastolic volume which is known as Starling’s Law. This law states that an increase in myocardial fibre contraction is proportional to the initial length of the muscle fibres This is shown in the graph

from the graph it shows as the end diastolic volume increase the stroke volume also increase

apart from that it shows that a greater increase in contractility as in exercise will increase the stroke volume at the same end-diastolic volume

as the end-diastolic volume increase it will stretches the muscle fibres and increases the energy of contraction , thus increasing the stroke volume until at a point of over stretching where the stroke volume will decrease

cardiac output will also increase with the increase in the stroke volume as long as there are no change in heart rate. In afterload the resistance is caused by systemic vascular resistance and it is determined by the diameter of the arterioles and pre-capillary sphincters As afterload of the systemic vascular resistance increase the stroke volume will be decrease as there will be increase resistance for the blood to flow out. This will decrease the cardiac output as the stroke volume is proportionate to the cardiac output Contractility is influenced by sympathetic nervous system When Beta adrenergic receptor is stimulated contractility will increase and so do the stroke volume and cardiac output. Hypertension is high blood pressure in the body Therefore when the blood fill in the ventricles it will increase the myocardial fibres hence will increase the stroke volume and the cardiac output .

As more blood has to be pump by the heart it will lead to hardening of the arteries or atherosclerosis

SUBJECT: PHYSIOLOGYNAMA: MOHD ZULHILMIE MOHD NASIR

Discuss the factors that influence fluid exchange across vascular capillary walls, including reference to processes that may lead to formation of oedema.

a) Increase capillary hydrostatic pressure -Arteriolar dilation -Venous constriction -Increased venous pressure -heart failure -Extracellular fluid volume expansionb) Decrease capillary oncotic pressure -Decrease plasma protein concentration -Severe liver failure( failure to synthesize protein ) -Protein malnutrition -Nephrotic syndrome( loss of protein in urine )c) Increase hydraulic conductance -Burn -Inflammation( release of histamine, cytokines )d) Impaired lymphatic drainage -Standing( lack of skeletal muscle compression of lymphatics ) -Removal or irradiation of lymph nodes -Parasitic infection of lymph nodes

All the factors described above will result in an increase of filtration pressure across capillary which also results in an increase of interstitial fluid volume( edema or swelling )

SUBJECT: ANATOMYNAME: MUHAMMAD CHE YAAKOB

20. Discuss the determinants of fluid flow across vascular capillary walls. Define oedema and describe the physiological and clinical circumstances in which it occurs.(45 marks)

Fluid will flow by osmosis across the capillary wall if membrane has aqueous pores and if there is a pressure difference across the membrane. The pressure difference can be a hydrostatic pressure difference, an effective osmotic pressure difference, or a combination of hydrostatic and effective osmotic pressures. In capillaries, fluid movement is driven by the sum of hydrostatic and effective osmotic pressures.

Solutes with reflection coefficients of 1.0 contribute most to the effective osmotic pressure. When the reflection coefficient is 1.0, the solute cannot cross the membrane, and it exerts its full osmotic pressure. In capillary blood, only protein contributes to the effective osmotic pressure, since it is the only solute whose reflection coefficient at capillary wall is approx. 1.0.the effective osmotic pressure contributed by protein is called the collidosmotic pressure or oncotic pressure.

Fluid movement across a capillary wall is driven by the starling pressures across the wall and is described by the Starling equation as follows:

Jv = Kf [(Pc – Pi) – (c - i)

Where

Jv = Fluid movement (ml/min)Kf = Hydraulic conductance (ml/min . mm Hg)Pc = Capillary hydrostatic pressure (mm Hg)Pi = Interstitial hydrostatic pressure (mm Hg)c = Capillary oncotic pressure (mm Hg)i = Interstitial oncotic pressure (mm Hg)

The Starling equation states that fluid movement across a capillary wall is determined by the net pressure across the wall, which is the sum of hydrostatic pressure and oncotic pressures. The direction of fluid movement can be either into or out of capillary. When net fluid movement is out of capillary into the interstitium into the capillary, it is called absorption. The magnitude of fluid movement is determined by the hydraulic conductance of the capillary wall. The hydraulic conductance determines how much fluid movement will be produced for a given pressure difference.

The net pressure, which is the net driving force, is the algebraic sum of the four pressures.

Oedema – an increase interstitial fluid

1. Oedema forms when the volume of interstitial fluid(due to the filtration out of the capillaries) exceeds the ability of the lymphatic to return it to the circulation.

2. It can form when the increase filtration or when lymphatic drainage is impaired.3. Various mechanisms for producing increase filtration –

Increased Pc (capillary hydrostatic pressure) Decreased c(capillary oncotic pressure) Increase Kf -hydrostatic conductance( destruction of the capillary wall)

4. Lymphatic drainage is impaired when the lymph nodes are surgically removed or irradiated in filariasis, parasitic infection of the lymph nodes or when there is lack of muscular activity.

Causes and examples of oedema formationCauses examplesIncreased Pc(capillary hydrostatic pressure) 1. arteriolar dilation

2. venous constriction3. increased venous pressure4. heart failure

5. extra cellular fluid(ECF) volume expansionDecreased c(capillary oncotic pressure) 1. decreased plasma protein concentration

2. severe liver failure(failure to synthesize protein)

3. protein malnutrition4. nephritic syndrome (loss protein in urine)

Increased Kf(hydrostatic conductance) 1. burn2. inflammation (release of histamine

cytokinase)Impaired lymphatic drainage 1. standing(lack of skeletal muscle compression

of lymphatic)2. removal or irradiation of lymph nodes3. parasitic infection of lymph nodes

SUBJECT: ANATOMYNAME: MUHAMMAD NABIL BIN MOHD WARID

QUESTIONS:Write an account of the anatomy of the coronary blood supply. Add a note on posible clinical presentations of a patient with a compromised blood supply to the myocardium. (45 marks)

ANSWERS:

Anatomy of the coronary blood supply

Coronary blood supply: right and left coronary artery branches of ascending aorta, which arise from aortic sinuses both run in the coronary groove

Right coronary artery: arises from right (anterior) aortic sinus gives off sino atrial nodal branch passes between right auricular appendage and infundibulum of the right ventricle (where

pulmonary artery emerges) passes vertically down in the A-V groove and then runs posteriorly supply right atrium and ventricle at inferior border – gives right marginal branch at crux of the heart – gives AV nodal branch on diaphragmatic surface – gives posterior interventricular branch (inferior IV branch) gives interventricular septal branches passes to the apex anastomoses by terminal arterioles with termination of left coronary artery at lower part of left

atrium

Left coronary artery: arises from left (left posterior) sinus emerges from between left auricular appendage and infundibulum of right ventricle passes backward along A-V groove gives off anterior interventricular branch near upper border of heart – passes to apex anterior interventricular artery may give a lateral (diagonal) branch parent trunk then named circumflex artery, which passes down in posterior A-V groove gives left marginal branch and anastomoses with right coronary artery below coronary sinus

Anastomoses: in inter ventricular septum in posterior wall (diaphragmatic surface) of left ventricle at the apex (interventricular arteries) in the atrioventricular groove (surface anastomoses)

Clinical narrowing of the coronary arteries (ischaemic heart disease), usually due to artheromatous

deposition in their walls, gives rise to conditions such as angina pectoris and myocardial infarction

ischaemic heart disease is the most common cause of death in the Western world. The anterior interventricular artery is most commonly affected

SUBJECT: ANATOMY

NAMA:22.How do changes in end diastolic volume influence ventricular performance and what is the physiological significance of this effect?

End diastolic volume = volume in the ventricle before ejection.

Explain using Frank-Starling relationship.

It states that volume ejected by the ventricle depends on the volume present in the ventricle at the end of diastole. End diastolic volume depends on venous return. So when venous return increase, EDV increase.

When the EDV increase, left ventricle diastolic pressure will increase, because of length tension relationship in ventricles, stroke volume also increase accordingly.

From the graph of stroke work versus ventricular end diastolic volume, when EDV is increase (heart dilate), ventricular contract more strongly, so more ventricular stroke work to reduce the size of ventricle. Therefore, more blood is pump out from the heart throughout the body. This is important during vigorous exercise as more oxygen is needed for action.

When EDV become very high, curve starts to bend and reaching the limit. So, ventricle is unable to “keep up” with venous return. EVP decrease so stroke volume decrease and heart starts to fail. For example, giving too much IV fluid in infusion too rapidly will cause heard to fail by increasing volume of blood entering ventricle during diastole. When ventricular cardiac muscle damage, ventricular fails to pump all the blood it receives. Therefore, blood built up in ventricle. EDP increase and at certain level, the ventricle unable to coupe the blood and stroke volume starts to fall away.

In heart failure (heart will dilate), a higher end diastolic pressure is required to achieve the same stroke work as in the normal heart. When heart is dilate the Law of Laplace more significant than Frank-starling law. Law of Laplace states that the greater the thickness of the wall (ventricular for example), the greater the pressure that can be developed to eject the blood. So, heart need to do more work to prevent it expending further. This eventually led to ventricular hypertrophy

End diastolic volume also reduces as the blood supplies to the heart reduce. For example, blood lost or dehydration will lead in reduction of end diastolic volume as venous return decrease, reduced the strength of contraction.

SUBJECT: ANATOMYNAMA:

.Write short notes ona) Poiseuille’s Lawb) the influence of the sympathetic nerves on cardiac functionc) the measurement of cardiac output

a) Pressure gradient = Resistance × Flow Q = P1-P2

R

P1 = Pressure higher than P2

P2 = Pressure lower than P1

Q = Blood flowR = Resistance

R = 8ηL Лr4

Poiseuille’s Law

Q = лr 4 ( P 1- P2 ) 8ηL

R is inversely proportional to r4

If the radius of the vessel is increased by double,the resistance will decrease by 16 times and vice versa.

b) Effect of sympathetic nerves on heart rate and contractility:

- increases the heart rate- increases the strength of muscle contraction- blood vessels –vasoconstriction (usually!)

Speed of effects :

a) onset is slower than parasympathetic nerves- noradrenaline is released more slowly than acetylcholine and the effect is

mediated by a second messenger system which is slower than an ion based system. b) effect lasts longer than parasympathetic nerves - signal is terminated by reuptake of noradrenaline back into presynaptic teminal.

c) the measurement of cardiac output

1)Fick’s methodAmount of blood entering or leaving = cardiac output

a) Use central or swan ganz line to sample right atrial or pulmonary venous blood and measure oxygen concentration.

b) Pulmonary venous blood of oxygen concentration is the same as concentration in the peripheral artery (because no oxygen is absorbed from blood in left ventricle or arteries) so sample peripheral arterial blood and measure oxygen concentration.

Determine oxygen concentration using haemoglobin saturation curves.

c) Amount of oxygen added by alveoli is determined by determining amount of air inspired and oxygen concentration in inspired and expired air.

2) Dye indicator dilution

a) Inject bolus of dye into peripheral veinb) Take rapid serial measurements of dye in arterial bloodc) The greater the cardiac output the faster the dye will become diluted in the arterial bloodd) Problem: Recirculation of dye

3) Thermal indicator dilution

a) Inject bolus of cold saline into peripheral veinb) Measure blood temperature change in pulmonary vein with electronic thermometer on

central venous catheter.c) The faster the temperature becomes warm the greater the cardiac outputd) No recirculation problem as saline is warmed in body

4) EF measurement

a) Ventriculography during coronary angiogramb) Ultrasound – echocardiographyc) Radioisotope-Multiple Gated Acquisition Scan (MUGA) –Inject Tc-99 labelled Red

Blood Cells.Gamma detector detects radioactive emission from Tc as it flows through the heart.

5) Bioimpedance-Pass electric current through the chest-resistance to current is altered by liquid flowing.

6) Magnetic Flow Meter attached to aorta-invasive.

SUBJECT: ANATOMYNAMA: NUR AWATIF AZMI

24.Discuss the contribution of systemic arterial baro-receptors to the control of arterial blood pressure

Arterial Baroreceptors

Def: It is a stretch receptor. It regulate of arterial blood pressure is accomplished by negative feedback systems incorporating pressure sensors

Location: Arterial baroreceptors are located in the carotid sinus (at the bifurcation of external and internal carotids) and in the aortic arch.

Innervations:

The sinus nerve, a branch of the glossopharyngeal nerve (IX cranial nerve), innervates the carotid sinus. The sinus nerve synapses in the brainstem.

The aortic arch baroreceptors are innervated by the aortic nerve, which then combines with the vagus nerve (X cranial nerve) travelling to the brainstem, bilateral vagotomy, therefore, denervates the aortic arch baroreceptors.

Arterial baroreceptors are sensitive to stretching of the walls of the vessels in which the nerve endings lie. Increased stretching augments the firing rate of the receptors and nerves, and recruits additional afferent nerves.

Mediated by autonomic nervous system.

Action:

The receptors of the carotid sinus respond to pressures ranging from 60-180 mmHg Receptors within the aortic arch have a higher threshold pressure and are less sensitive

than the carotid sinus receptors. Therefore, the carotid sinus receptors are normally the dominant arterial baroreceptor.

Maximal carotid sinus sensitivity occurs near the normal mean arterial pressure.

This "set point" changes during hypertension, heart failure, and other disease states.

Therefore, at a given mean arterial pressure, decreasing the pulse pressure decreases the baroreceptor-firing rate. This is important during conditions such as hemorrhagic shock in which pulse pressure as well as means pressure decreases. The combination of reduced mean pressure and reduced pulse pressure reinforces the baroreceptor reflex.

How it response to a sudden increase in arterial pressure and how do they alter cardiovascular control:

A decrease in arterial pressure (mean, pulse or both) results in decreased baroreceptor firing.

The "cardiovascular centre" within the medulla responds by increasing sympathetic outflow and decreasing parasympathetic outflow.

Under normal physiological conditions, baroreceptor firing exerts a tonic inhibitory influence on sympathetic outflow from the medulla.

Therefore, hypotension results in a disinhibition of the medullary centers.

These autonomic changes cause vasoconstriction (increased systemic vascular resistance, SVR), tachycardia and positive inotropy.

The latter two changes increase cardiac output. The increases in cardiac output and SVR lead to a partial restoration of arterial pressure.

SUBJECT: PHYSIOLOGYNAMA: NUR AZUATUL AKMAL KAMALUDIN

QUESTIONS: discuss how the heart functions as a pump by describing the sequence of mechanical events that occurs in the single cardiac cycle(References: human physiology Costanzo and Cardiac cycle website)

ANSWERS:

Overview of Cardiac Cycle

Divided into 2 stages- I. systole

II. diastole

These stages are further divided into 7 phases-for easier explanationThe phases are:

1. atrial contraction2. isovolumetric contraction3. rapid ventricular ejection4. reduced ejection5. isovolumetric relaxation6. rapid ventricular filling7. reduced filling

The Wigger’s diagram in explaining the whole cycle contains information on:

1. aortic pressure2. left ventricular pressure3. left atrial pressure4. ventricular volume5. heart sounds6. phases displayed on ECG7. venous pulse/jugular pulse-

sometimes (not shown in this diagram)

intro: A single cardiac cycle Refers to mechanical and electrical

activities of heart Consists of 7 phases ECG is used to mark the electrical events in the cardiac cycle Cycle begis with the depolarisation and contraction of the atria (atrial systole)

Atrial systole1. Key: AV(mitral and tricuspid) Valves open, SL(aortic and pulmonary) valves

close2. First phase of cardiac cycle3. Represented as P-wave by ECG, which means, electrical depolarisation of the atria.4. Atrial depolarisations cause the atrial musce to contract.5. As atrial muscles contract, pressure in atrial chambers increases.6. This generates pressure gradient across the open AV valves, thereby causing rapid

flow of blood into the ventricles7. ventricles are relaxed during this time8. active blood filling prior to atrial systole causes the ventricular volume to further

increase9. The blip in left ventricular pressure corresponds to this active blood filling.10. Ventricular volume at this phase is maximal, normally about 120 ml and termed as

end-diastolic volume.11. retrograde atrial flow back into Vena cavae is impeded by venous return(inertial

effect) and wave of contraction throughout atria (milking effect)12. However, atrial contraction still produced small increase in venous pressure that can

be noted as a-wave of the jugular pulse.Just following the a-peak is the x-descent.13. The 4th heart sound sometimes can be heard during this phases. This sound is caused

by vibration of ventricular wall during atrial contraction. Usually, it can be only heard if the ventricular compliance is reduced (ventricle is stiff!) as occurs in person with VENTRICULAR HYPERTROPHY OR HIGH BLOOD PRESSURE.

Isovolumetric Ventricular Contraction.1. key: all AV and SL valves close2. this is the second phase of cardiac cycle3. It is initiated as QRS complex (beginning) in ECG, representing the ventricular

depolarisation.4. As ventricles depolarise, the excitation-contraction coupling leads the ventricular muscles to

contract.5. this contraction leads to the increase in left ventricular pressure6. As the increase of left ventricular pressure exceeds the left atrial pressure, the mitral valve

(tricuspid at right) closes.7. The closure of these AV valves produces the 1st heart sound.8. this heart sound normally split because mitral valve closes slightly before tricuspid valve.

(~0.04s)9. ventricular pressure increases dramatically during this phase but the ventricular volume

remain unchanged since all valves are closed.(SL valves have remained closed from the previous cycle)

10. atrial pressure increase during this phase due to continuous venous return and possible bulging back of the AV valves into the atrial chambers

11. The c-wave noted in the jugular pulse (venous pressure) is thought to occur due to increased right atrial pressure that results from bulging of tricuspid valve leaflets back into right atrium.  Just after the peak of the c-wave is the x'-descent.

Rapid ventricular ejection1. Key: SL valves (aortic and pulmonary) open now, AV valves (mitral and tricuspid)

remain close.2. this is the third phase in cardiac cycle3. Ventricles continue to contract and the ventricular pressure reaches its highest value.4. When the ventricular pressure becomes greater than aortic and pulmonary pressure, the SL

Valves open.5. blood now is rapidly ejected from ventricles to aorta and pulmonary artery, this blood flow is

driven by pressure gradient that exists between ventricles and these outflow tracts (aorta and pulmonary trunk)

6. Most of stroke volume is ejected during rapid ejection, thus decreasing the ventricular volume drammatically.

7. Concomitantly, aortic pressure (outflow tracts pressure) increases as a result of the large volume of blood that is suddenly added to aorta (outflow tracts).

8. Also, atrial filling begins here. Atrial pressure initially decreases as the atrial base is pulled downward, expanding the atrial chamber and the atrial pressure slowly increases as blood returns to heart from pulmonary and systemic circulation.(this blood is for the ejection purpose of the next cardiac cycle )

9. The end of this phase coincides with the ST segment of ECG and end of ventricular contraction.

10. No heart sounds are ordinarily noted during ejection.  The opening of healthy valves is silent.  The presence of sounds during ejection (i.e., ejection murmurs) indicate valve disease or intracardiac shunts

Reduced ventricular ejection1. key: SL valves (aortic and pulmonary) still open, AV valves (mitral and tricuspid)

remain close2. This is the fourth phase in cardiac cycle.3. The ventricles begin to repolarize now, approximately 150-200 msec after the QRS, thus

marked as the beginning of T-wave on ECG.4. Ventricular pressure falls as ventricular muscles are no longer contracting.5. Because the SL valves are still open, blood continues to be ejected from ventricles to aorta and

pulmonary trunk, albeit at a reduced rate.6. even though blood continues to be added to aorta, blood is running off into the arterial tree at

even faster rate, thus causing the aortic pressure to fall 7. Atrial pressures continue to rise due to venous return (left atrial pressure due to blood from

lungs).

Isovolumetric Ventricular Relaxation 1. key:all valves close2. This is the fifth phase of cardiac cycle.3. This phase begins after ventricles are fully repolarized, marked by the end of T-wave on

ECG.4. Because left ventricle is relaxed, the left ventricular pressure decreases dramatically.5. When the left ventricular pressure decreases below than the aortic pressure, the aortic valve

closes. The aortic valve closes slightly before the pulmonary valve, producing the 2nd heart sound.6. Inspiration delays the closure of pulmonary valve (due to increased venous return),

exaggerating the difference in closure time between the aortic and pulmonary valves, which causes splitting of the 2nd heart sound.

7. At the point where aortic valve closes, aortic pressure curve shows blip(dicrotic notch or incisura)

8. Since all valves are closed again, no blood is ejected, nor is being filled into venticles, thus ventricular volume remain constant.

9. the volume of blood remains in ventricles now are called end-systolic volume, and normally it is about 50 ml. Difference between end diastolic volume and end systolic volume which is ~70 ml represents the stroke volume for each cardiac cycle.

10. Atrial pressures continue to rise due to venous return.

Rapid Ventricular Filling

1. key:AV valves (tricuspid and mitral) open2. this is the sixth phase of cardiac cycle3. Ventricular pressure falls to its lowest pressure, below than the atrial pressure.4. This causes the AV valves open and ventricular filling begins. The ventricles continue to relax

despite the inflow, which causes intraventricular pressure to continue to fall by a few additional mmHg.

5. Once AV valves open, ventricles begin to fill with blood from atria, ventricular volume increases rapidly.

6. The opening of the AV valves causes a rapid fall in atrial pressures and a fall in the jugular pulse.  The peak of the jugular pulse just before the valve opens is the v-wave.  This is followed by the y-descent of the jugular pulse

7. Ventricular pressure remains low, however because ventricles are still relaxed and compliant.(compliant=volume can be added without changing the pressure).

8. Rapid blood flow produces 3rd heart sound, which is normal in children, not normally heard in adult. In adult, it can be heard in individu with ventricular dilation.

9. During this phase also, aortic pressure decreases as blood runs off from aorta into the arterial tree, to veins and then back to heart.

Reduced ventricular Filling1. key: AV valves open2. This is the seventh phase of cardiac cycle.3. This phase, also known as diastasis is the longest phase in cardiac cycle.4. Filling occurs at slower rate than the previous phase.5. End of this phase marks the end of diastole, at which point, ventricular volume = end

diastolic volume.6. As the ventricles continue to fill with blood and expand, they become less compliant and the

intraventricular pressures rise.  This reduces the pressure gradient across the AV valves so that the rate of filling falls.

7. Aortic pressure (and pulmonary arterial pressure) continues to fall during this period

SUBJECT: ANATOMYNAME: NUR HAKIMIN B. NORDIN

Question: Summer 2004: Describe the changes in cardiac function that occur with the changes in venous return. Refer to the significance of this phenomena in patients with heart failure.

Answer:Venous pressure in the body is very low (cardiovascular pressure: 2-6 mmHg). At this low pressure, the veins can hold large volumes of blood due to it’s high capacitance. Flow into right heart is called venous return. Venous return is influenced by blood volume or venous compliance, cardiac output and total peripheral resistance.According to Frank-Starling relationship, increased venous return will provides more blood for each stroke volume. In other condition, if the total peripheral resistance is increase, both the total cardiac output and hence the venous return are decreased. This means that blood is retained on the arterial side. While in shock, venous return falls resulting the falls of cardiac output. If a person perform valsalva manouver, this will greatly reduces venous return.Heart failure is a condition in which the heart is unable to pump sufficient blood to meet the normal requirements of the tissues, or can only do so in the presence of an abnormally high filling pressure. For instance, Congestive Heart Failure indicates the inability of the heart to pump enough blood to meet the body’s metabolic requirements for oxygen and nutrients leading to discrepancies between myocardial oxygen supply and demand. The hearts primary function is to pump blood coming into the ventricles from the lower pressure venous system against the higher pressure arterial system. Impairment of this pumping ability results in inadequate emptying at the venous side and inadequate blood delivery to the pulmonary and systemic circulation, hence heart failure

SUBJECT: ANATOMYNAMA: NORHAZURA ABDUL WAHAB

27. Summer 2004, Q4How is the mean systemic arterial blood pressure regulated in the short term? (30 marks)

Mean systemic arterial pressure (MAP) = diastolic pressure (DP) + 1/3 (Pulse pressure) MAP is important since it is the pressure driving blood through organs/tissues averaged over

the cardiac cycle. Because of this, it is the major cardiovascular variable regulated by the body. This regulation

is achieved by controlling the determinants of MAP, i.e. CO and total peripheral resistance (TPR).

MAP = CO x TPR MAP could then be restored to normal levels by a compensating increase in both TPR (to

above normal) and CO (towards normal). Changes in these factors not only initiate changes in MAP, but also can act to then minimize

these changes in MAP. In controlling blood pressure only in short term, compensatory reflex mechanism,

baroreceptor reflexes is used. Like all reflex systems, these include receptors (arterial baroreceptors) sensitive to changes in

the variable being regulated (MAP), afferent nerves connecting the receptors to an integrating centre (medullary cardiovascular centre) where the information is processed, and efferent pathways (sympathetic + parasympathetic NS, & others) by which compensatory changes in effector organs (heart, arterioles, veins) are then initiated.

Baroceptors:a) Arterial Baroreceptors sensibly enough are located in the arterial system, and consist of the

carotid sinus and aortic arch baroreceptors - these are sensitive to the degree of wall stretch, which depends on the MAP.

b) Cardiopulmonary Baroreceptorsi. Cardiac chambers

ii. Veno-atrial regionsiii. Pulmonary arteries

Arterial Baroceptors:a) Carotid sinus: widened area of internal carotid artery, at the points of origin from

common carotid arteries. Baroreceptors are located in this dilation. b) Aortic arch: wall of the arch, the receptors are located in the adventitia of the vessels.

Baroreflex:1) A pressure buffer system2) Negative feedback system (P, rate of firing, trigger baroreflex, bring to target back -

ve feedback) 3) Pressure fluactuations from the set point are minimized4) ¯ MAP ¯ wall stretch ¯ discharge frequency in the afferent fibres. The resulting

reflex response via the medullary CV centre causes sympathetic input to the heart ( -HR & SV CO), arterioles ( TPR) and veins (venous press. EDV SV CO).

5) While ¯ing parasympathetic input to the heart ( HR CO). The in CO & TPR will therefore cause a compensatory rise in MAP.

Example of baroreflex triggers:1) Supine to upright ¯ body venous pooling ¯venous return ¯CO ¯ MAP2) Haemorrhage ¯ blood volume ¯ venous return ¯CO ¯MAP

Influence of pulse pressure-The carotid receptors respond to both to sustained pressure and pulse pressure. A decline in carotid PP without any change in mean P decrease the rate of baroreceptor discharge and provokes an increase in BP and tachycardia.

SUBJECT: BIOCHEMISTRYNAMA: NURUL SHIMA ISMAIL

QUESTIONS: Discuss the relationship between the oxygen-binding curves of the myoglobin and haemoglobin and the structures of these proteins.

ANSWERS:

Myoglobin is a haemoglobin-like, iron-containing pigment (haemprotein) found in muscle fibres where it serves as an intracellular storage site for oxygen. It consists of a single alpha polypeptide chain (monomeric heme protein) and binds only one oxygen molecule (as opposed to haemoglobin which binds 4 oxygen molecules). The tertiary structure of myoglobin is that of a typical water soluble globular protein. Its secondary structure is unusual in that it contains a very high proportion (75%) of -helical secondary structure. A myoglobin polypeptide is comprised of 8 separate right handed -helices, designated A through H, that are connected by short non helical regions. Amino acid R-groups packed into the interior of the molecule are predominantly hydrophobic in character while those exposed on the surface of the molecule are generally hydrophilic, thus making the molecule relatively water-soluble. Each myoglobin molecule contains one heme prosthetic group inserted into a hydrophobic cleft in the protein. Each heme residue contains one central coordinately bound iron atom that is normally in the Fe2+, or ferrous, oxidation state. The oxygen carried by hemeproteins is bound directly to the ferrous iron atom of the heme prosthetic group. Oxidation of the iron to the Fe3+, ferric, oxidation state renders the molecule incapable of normal oxygen binding. Hydrophobic interactions between the tetrapyrrole ring and hydrophobic amino acid R groups on the interior of the cleft in the protein strongly stabilize the heme protein conjugate. Carbon monoxide also binds coordinately to heme iron atoms in a manner similar to that of oxygen, but the binding of carbon monoxide to heme is much stronger than that of oxygen. The highest concentration of myoglobin are found in skeletal and cardiac muscle which requires large amounts of oxygen because of the need for large amounts of energy during contraction.

Adult hemoglobin is a [(2):(2)] tetrameric hemeprotein found in erythrocytes where it is responsible for binding oxygen in the lung and transporting the bound oxygen throughout the body where it is used in aerobic metabolic pathways. Each subunit of a hemoglobin tetramer has a heme prosthetic group identical to that described for myoglobin. Although the secondary and tertiary structure of various hemoglobin subunits are similar, reflecting extensive homology in amino acid composition, the variations in amino acid composition that do exist impart marked differences in hemoglobin's oxygen carrying properties. In addition, the quaternary structure of hemoglobin leads to physiologically important allosteric interactions between the subunits, a property lacking in monomeric myoglobin which is otherwise very similar to the -subunit of hemoglobin. Comparison of the oxygen binding properties of myoglobin and hemoglobin illustrate the allosteric properties of hemoglobin that results from its quaternary structure and differentiate hemoglobin's oxygen binding properties from that of myoglobin. The curve of oxygen binding to hemoglobin is sigmoidal typical of allosteric proteins in which the substrate, in this case oxygen, is a positive homotropic effector. When oxygen binds to the first subunit of deoxyhemoglobin it increases the affinity of the remaining subunits for oxygen. As additional oxygen is bound to the second and third subunits oxygen binding is further, incrementally, strengthened, so that at the oxygen tension in lung alveoli, hemoglobin is fully saturated with oxygen. As oxyhemoglobin circulates to deoxygenated tissue, oxygen is incrementally unloaded and the affinity of hemoglobin for oxygen is reduced. Thus at the lowest oxygen tensions found in very active tissues the binding affinity of hemoglobin for oxygen is very low allowing maximal delivery of oxygen to the tissue.

Allosteric behaviour results in an oxygen dissociation curve (a plot of saturation of oxygen-binding sites vs partial pressure of oxygen) that is sigmoidal for haemoglobin, rather than hyperbolic. Hyperbolic curves are exhibited by monomeric molecules such as myoglobin, the monomeric alpha chain, and other non-cooperative molecules such as haemoglobin H. The allosteric oxygen binding properties of hemoglobin arise directly from the interaction of oxygen with the iron atom of the heme prosthetic groups and the resultant effects of these interactions on the quaternary structure of the protein. When oxygen binds to an iron atom of deoxyhemoglobin it pulls the iron atom into the plane of the heme. Since the iron is also bound to histidine F8, this residue is also pulled toward the plane of the heme ring. The conformational change at histidine F8 is transmitted throughout the peptide backbone resulting in a significant change in tertiary structure of the entire subunit. Conformational changes at the subunit surface lead to a new set of binding interactions between adjacent subunits. The latter changes include disruption of salt bridges and formation of new hydrogen bonds and new hydrophobic interactions, all of which contribute to the new quaternary structure. The latter changes in subunit interaction are transmitted, from the surface, to the heme binding pocket of a second deoxy subunit and result in easier access of oxygen to the iron atom of the second heme and thus a greater affinity of the hemoglobin molecule for a second oxygen molecule. The tertiary configuration of low affinity, deoxygenated hemoglobin (Hb) is known as the taut (T) or tight state. Conversely, the quaternary structure of the fully oxygenated high affinity form of hemoglobin (HbO2) is known as the relaxed (R) state.

In the context of the affinity of hemoglobin for oxygen there are four primary regulators, each of which has a negative impact. These are CO2, hydrogen ion (H+), chloride ion (Cl-), and 2,3-bisphosphoglycerate (2,3BPG, or also just BPG). Some older texts abbreviate 2,3BPG as DPB. Although they can influence O2 binding independent of each other, CO2, H+ and Cl- primarily function as a consequence of each other on the affinity of hemoglobin for O 2. We shall consider the transport of O2 from the lungs to the tissues first. In the high O2 environment (high pO2) of the lungs there is sufficient O2 to overcome the inhibitory nature of the T state. During the O2 binding-induced alteration from the T form to the R form several amino acid side groups on the surface of hemoglobin subunits will dissociate protons as depicted in the equation below. This proton dissociation plays an important role in the expiration of the CO2 that arrives from the tissues (see below). However, because of the high pO2, the pH of the blood in the lungs (~7.4 - 7.5) is not sufficiently low enough to exert a negative influence on hemoglobin binding O2. When the oxyhemoglobin reaches the tissues the pO2 is sufficiently low, as well as the pH (~7.2), that the T state is favored and the O2 released.

4O2 + Hb <--------> nH+ + Hb(O2)4

If we now consider what happens in the tissues, it is possible to see how CO2, H+, and Cl- exert their negative effects on hemoglobin binding O2. Metabolizing cells produce CO2 which diffuses into the blood and enters the circulating red blood cells (RBCs). Within RBCs the CO 2 is rapidly converted to carbonic acid through the action of carbonic anhydrase as shown in the equation below:

CO2 + H2O --------> H2CO3 ------> H+ + HCO3-

The bicarbonate ion produced in this dissociation reaction diffuses out of the RBC and is carried in the blood to the lungs. This effective CO2 transport process is referred to as isohydric transport. Approximately 80% of the CO2 produced in metabolizing cells is transported to the lungs in this way. A small percentage of CO2 is transported in the blood as a dissolved gas. In the tissues, the H+

dissociated from carbonic acid is buffered by hemoglobin which exerts a negative influence on O2

binding forcing release to the tissues. As indicated above, within the lungs the high pO2 allows for effective O2 binding by hemoglobin leading to the T to R state transition and the release of protons. The protons combine with the bicarbonate that arrived from the tissues forming carbonic acid which then enters the RBCs. Through a reversal of the carbonic anhydrase reaction, CO2 and H2O are produced. The CO2 diffuses out of the blood, into the lung alveoli and is released on expiration. In addition to isohydric transport, as much as 15% of CO2 is transported to the lungs bound to N-terminal amino groups of the T form of hemoglobin. This reaction, depicted below, forms what is called carbamino-hemoglobin. As indicated this reaction also produces H+, thereby lowering the pH in tissues where the CO2 concentration is high. The formation of H+ leads to release of the bound O2 to the surrounding tissues. Within the lungs, the high O2 content results in O2 binding to hemoglobin with the concomitant release of H+. The released protons then promote the dissociation of the carbamino to form CO2 which is then released with expiration.

CO2 + Hb-NH2 <-----> H+ + Hb-NH-COO-

As the above discussion demonstrates, the conformation of hemoglobin and its oxygen binding are sensitive to hydrogen ion concentration. These effects of hydrogen ion concentration are responsible for the well known Bohr effect in which increases in hydrogen ion concentration decrease the amount of oxygen bound by hemoglobin at any oxygen concentration (partial pressure). Coupled to the diffusion of bicarbonate out of RBCs in the tissues there must be ion movement into the RBCs to maintain electrical neutrality. This is the role of Cl- and is referred to as the chloride shift. In this way, Cl- plays an important role in bicarbonate production and diffusion and thus also negatively influences O2 binding to hemoglobin.

Representation of the transport of CO2 from the tissues to the blood with delivery of O2

to the tissues. The opposite process occurs when O2 is taken up from the alveoli of the lungs and the CO2 is expelled. All of the processes of the transport of CO2 and O2 are not shown such as the formation and ionization of carbonic acid in the plasma. The latter is a major mechanism for the transport of CO2 to the lungs, i.e. in the plasma as HCO3

-. The H+ produced in the plasma by the ionization of carbonic acid is buffered by phosphate (HPO4

2-) and by proteins. Additionally, some 15% of the CO2 is transported

from the tissues to the lungs as hemoglobin carbamate.

 Salt-bridges between alpha and beta subunits help stabilise the T state (low oxygen affinity) of haemoglobin. These interactions are clustered into four groups. Zoom in on each group in turn and then click on the button below to see the conformational changes that occur on oxygen binding. The salt bridges between subunits are broken when oxygen binds and haemoglobin converts to the R state (high oxygen affinity). The binding of oxygen in the centre of a monomer induces conformational changes due to the movement of the iron atom and the proximal histidine which are propagated via helix F to the inter-subunit interface.

The significance of the sigmoidal curve is that it means that haemoglobin A becomes highly saturated at high oxygen partial pressures, and releases a significant amount of oxygen at pressures which are fairly low, but not extremely so. Contrast this to the hyperbolic myoglobin curve, where even at the low partial pressure of 20 mmHg, the oxygen-carrier is still almost totally saturated. 20mmHg is in fact the partial oxygen pressure in the capillaries of active muscles. Aterial pressure is 100mmHg. Haemoglobin A is 50% saturated at 26mmHg, while 50% saturation of myoglobin occurs at only 1mmHg. The dissociation curve is sigmoidal in shape because binding of the 1st O2 molecule increases the affinity of haemoglobin for oxygen, making it easier for the next oxygen molecule to bind. The oxygen affinity of haemoglobin is modified by several factors:

binding of oxygen- this increases oxygen affinity binding of carbon dioxide to other specific sites- this decreases the oxygen affinity binding of protons to specific basic groups- decreases the oxygen affinity binding of certain organic phosphates - decreases the oxygen affinity

Reference:

o http://diatronic.co.uk/nds/webpub/dissociation_curve.htm o http://www.cryst.bbk.ac.uk/PPS2/course/section12/haemogl1.html o http://web.indstate.edu/thcme/mwking/hemoglobin-myoglobin.html