MDSC 1102 PBL PROBLEM 4 BY ARVIND SEECHARAN(FUTURE DOCTOR EXTRAORDINAIRE)
Learning Objective 1• Discuss the blood supply and venous and lymphatic drainage of the heart
Blood supply of heartArterial supply:• Heart is supplied by right and left coronary arteries• These surround the heart like an inverted crown
Heart (sternocostal surface) Ascending aortaRight auricle Left coronary arteryRightcoronaryartery Circumflex artery Anterior interventricular artery Right marginal Great cardiac artery vein Pulmonary trunk
Heart (base and diaphragmatic surface) Left atrium Right atriumCircumflexartery Right coronary artery Left ventricle Right ventricle
• Right coronary artery:• Origin:• Branch of ascending aorta• Begins from the anterior aortic (right coronary) sinus• Course:• Runs between the right auricle and pulmonary trunk, enters the anterior part of coronary sulcus• Runs to the right in the anterior part of coronary sulcus• Winds around the right margin of heart• Then runs to the left in the posterior part of coronary sulcus• Termination:• Anastomoses with circumflex branch of left coronary artery
Branches of right coronary artery • Right conus artery • Atrial branches • Ventricular branches • Right marginal arteryAtrial • Posteriorbranch interventricular artery Right marginal Right artery conus Ventricular artery branch
• Branches:• Right conus branch supplies lower part of pulmonary trunk and upper part of right ventricle• Atrial branches supply right atrium, one of them supply SA node (artery of SA node)• Ventricular branches supply right ventricle• Right marginal artery – is one of the ventricular branch, runs along the inferior margin of heart• Posterior inter-ventricular branch (posterior descending) runs in the posterior inter-ventricular groove, terminates by anastomosing with anterior inter- ventricular artery, supplies posterior part of inter- ventricular septum and adjoining part of right and left ventricles
• Area of distribution of right coronary artery:• Right atrium• Right ventricle except a part on the sternocostal surface near the anterior inter-ventricular groove• Part of the left ventricle on the inferior surface near the posterior inter-ventricular groove• Posterior part of inter-ventricular septum• Most of the conducting system of heart (SA node, AV node, right AV bundle) except left AV bundle
• Left coronary artery:• Origin:• Branch of ascending aorta• Arises from the left posterior aortic sinus• Course:• Runs between the left auricle and pulmonary trunk• Reaches the anterior part of coronary sulcus• As it enters the coronary sulcus it terminates by dividing to 2 branches• Termination:• Divides into anterior inter-ventricular and circumflex branches
Heart (sternocostal surface) Ascending aorta Left coronary arteryRightcoronaryartery Circumflex artery Anterior interventricular artery Great cardiac vein Pulmonary trunk
Heart (base and diaphragmatic surface) Left atrium Right atriumCircumflexartery Right coronary artery Posterior inter- ventricular artery Left ventricle Right ventricle
• Anterior interventricular artery (anterior descending):• Branch of left coronary artery• Runs on the sternocostal surface in the anterior inter- ventricular groove with the great cardiac vein• Terminates by anastomosing with posterior inter- ventricular artery• Branches:• Left conus artery – supplies upper part of right ventricle and lower part of pulmonary trunk• Ventricular branches – supply the left ventricle and part of right ventricle near the anterior inter-ventricular groove. One of the ventricular branch is large and is known as left diagonal artery• Septal branches – supply anterior part of inter- ventricular septum
• Circumflex artery:• Branch of left coronary artery• Curves around the left margin of heart in the coronary sulcus• Enters the posterior part of coronary sulcus• Terminates by anastomosing with right coronary artery• Branches:• Atrial branches – supply left atrium• Ventricular branches – supply left ventricle• Left marginal artery – runs along the left margin of heart, supplies left ventricle
• Area of distribution of left coronary artery:• Left atrium• Left ventricle except a part on the diaphragmatic surface near the posterior interventricular groove• Part right ventricle on the anterior surface near the anterior interventricular groove• Anterior part of interventricular septum• Left AV bundle
• Venous drainage of heart:• Coronary sinus and its tributaries• Anterior cardiac veins• Thebesian veins• Coronary sinus:• Largest vein of heart, about 3 cm long• Situated in the posterior part of coronary sulcus between the left atrium and left ventricle• Terminates by opening into the smooth part of right atrium• Opening is guarded by valve of coronary sinus (Thebasian valve)• Receives most of the veins of heart
Coronary sinus and its tributaries Left atrium Oblique vein of left atrium Right atriumGreat cardiac veinCoronary sinus Small cardiac vein Posterior vein of left ventricle Left ventricle Right ventricle Middle cardiac vein
• Tributaries of coronary sinus:• Great cardiac vein• Small cardiac vein• Middle cardiac vein• Posterior vein of left ventricle• Oblique vein of left atrium• Great cardiac vein:• Situated in the anterior interventricular groove and anterior part of coronary sulcus• Small cardiac vein:• Situated in the posterior part of coronary sulcus between right atrium and right ventricle
• Middle cardiac vein:• Situated in the posterior inter-ventricular groove• Posterior vein of left ventricle:• Situated on the diaphragmatic surface of left ventricle• Oblique vein of left atrium (of Marshall):• Situated on the posterior surface of left atrium• Anterior cardiac veins:• 3 to 4 veins situated on the sternocostal surface of right ventricle• Terminate by opening into the right atrium
• Thebasian veins (venae cordis minimae):• Small veins situated in the myocardium of all the chambers• Terminate by opening into all chambers
LYMPHATIC DRAINAGE OF THE HEART• The lymphatics of the heart consist of small lymph vessels in the connective tissues of the tunica intima and media, which drain into an extensive epicardial lymphatic plexus.• Efferent vessels from the epicardial plexus converge in the cardiac sulci to form right and left cardiac collecting lymph trunks, which run along with branches of the coronary arteries towards the root of the ascending aorta and pulmonary trunk.
LYMPHATIC DRAINAGE OF THE HEART• Here they converge once again to form two lymph vessels, one draining the left trunks into the inferior tracheobronchial lymph nodes and the other draining the right trunks into the left brachiocephalic nodes
Learning Objective 2• Discuss the causes of ischemic heart disease and note the influence of diet, age, gender, life-style (stress), habits (smoking), obesity and hypertension
What is Ischemic heart disease• Ischemic heart disease (IHD), or myocardial ischaemia, is a disease characterized by ischaemia (reduced blood supply) of the heart muscle, usually due to coronary artery disease (atherosclerosis of the coronary arteries).
Ischemic heart disease• The principal cause of the ischemic heart disease is the reduction of the amount of blood which the arteries provide for the heart to function at normal parameters
• When you have ischemic heart disease ischemia the heart muscle is damaged because it doesn’t receive the needful oxygen and this is the cause of ischemia. A heart attack occurs when the blood vessels are completely closed.• Ischaemia refers to an insufficient amount of blood. The coronary arteries are the only source of blood for the heart muscle. If this coronary arteries are blocked, the blood supply will reduce. The atherosclerosis is one of the most common cause of the ischemic heart disease.
• At the beginning the coronary arteries or even their branches are becoming narrow or they are closed because of the debris flowed into the blood. This might feel like angina.
• The treatment must involve advice regarding a change in patients’ life style, avoiding unhealthy behavior like smoking, alcoholism and unhealthy diet. In the case of diabetes and hypertension strict control is required in order to achieve the best results and increase life expectancy.
Causes of Ischemic Heart Disease• Ischemic heart disease doesn’t have known causes responsible for its development, however a multitude of risk factors have been identified: – Smoking – Abdominal obesity – Diabetes mellitus – Heredity – Sedentary or stressful lifestyle – Age – Gender (men are more prone towards cardiac diseases than women) – Hypertension and hypercholesterolemia are major ischemic heart disease causes.
Poor Diet• A poor diet, rich in saturated fats can contribute to increasing blood cholesterol levels.• Hypercholesterolemia is one of the major causes responsible for the development of ischemic heart disease as a high Low Density Lipoproteins also known as ‘bad‘ cholesterol level can lead to the narrowing of the coronary arteries walls.
Poor Diet• As a result, a fatty build-up gathers in form of plaque obstructing the blood flow and creating blockages, over the heart muscle, the myocardium, doesn’t receive enough oxygen resulting in cardiac ischemia.• The formation of blood clothes and heart damages and tissue necrosis that leads to myocardial infraction may follow
Hypertension• Hypertension can also be the cause of ischemic heart disease, as elevated blood pressure can be harmful to the heart and lead in time to heart damages and ischemic heart disease.• One of the most important prevention measures for hypertensive patients is regular control and adequate medication.
Heredity• Heredity is another ischemic heart disease cause, as it has been demonstrated that genetic factors are responsible for the development of this condition and those with a family history of cardiac disease have to be extra cautious and avoid dangerous behaviours.
Gender• Gender has been pointed out as another risk factor for ischemic heart disease as males are more prone than women to develop the disease
Age• Age (increasing) can increase the incidence of cardiac diseases especially among women.
Smoking• Smoking along with an unhealthy sedentary lifestyle can also increase the probability of developing cardiac problems. Smoking cessation reduces whatsoever the severity of or complications after being diagnosed with a cardiac disease.
Diabetes• Diabetes is known to be other major ischemic heart disease risk factor, as patients suffering of diabetes can also develop coronary heart disease; myocardial infraction is known to be the major cause of morbidity among diabetic patients.• Due to the fact that in their cases the disease doesn’t show typical symptoms (silent ischemia) they must periodically attend medical controls and take periodical tests and also lead a strict diet.
• Another debatable cause of ischemic heart disease is stress, as it is believed that people with a type A personality defined by hyperactivity and a stressful lifestyle are more prone to develop heart conditions
Learning Objective 3• Discuss the biochemistry of plasma lipoproteins and the risks associated with an abnormal lipid profile.
Lipoprotein Structure and FunctionAre conjugated proteins, composed of core and surface • LP core – Triglycerides – Cholesterol esters • LP surface – Phospholipids – Proteins – Cholesterol
• Lipids are water insoluble• Present in the blood in the form of lipoproteins which are water soluble• They have an outer polar surface, which makes them water soluble.
Separation by ultracentrifugation• Four distinct groups based on their density• Chylomicron (d<0.96),• Very low density lipoprotein(VLDL, d=0.96-1.006)• Low density lipoprotein (LDL, d=1.006-1.063)• High density lipoprotein (HDL, d=1.063-1.21).
Separation by Electrophoresis Based on difference in their mobilization in an electric field
Plasma Lipoproteins Classes & FunctionsChylomicrons – Synthesized in small intestine (mucosal cells ) – To mobilize dietary lipids – Transport dietary lipids – 98% lipid, large sized, lowest density – Apo B-48 • Receptor binding – Apo C-II • Lipoprotein lipase activator – Apo E • Remnant receptor binding
Chylomicron Metabolism• Nascent chylomicron (apo B-48, apo–A) before they enter circulation• Mature chylomicron (+apo C & apo E)• Lipoprotein lipase found on the surface of endothelial cells lining the capillaries in muscle and adipose tissues removes the fatty acids of triglycerides• Chylomicron remnant – Apo C removed – Removed in liver
• Substantial portion of the phospholipid, apo-A and apo-C are transferred to HDLs during the process of fatty acid removal• Chylomicron remnant containing primarily cholesterol.• apo-E and apo-B-48 are taken up by the liver though the interaction with the chlyomicron remnant receptor
Plasma Lipoproteins Classes & Functions• Very Low Density Lipoprotein (VLDL) – Synthesized in liver – Transport endogenous triglycerides (liver to peripheral tissues – 90% lipid, 10% protein – Apo B-100 • Receptor binding – Apo C-II • LPL activator liberates free fatty acids that are taken up by the adipose tissue and muscle – Apo E • Remnant receptor banding
VLDL Metabolism• Nascent VLDL (B-100) + HDL (apo C & E) = VLDL• LPL hydrolyzes TG forming IDL – IDL loses apo C-II (reduces affinity for LPL)• 75% of IDL removed by liver – Apo E and Apo B mediated receptors• 25% of IDL converted to LDL by hepatic lipase – Loses apo E to HDL
Plasma Lipoproteins Classes & Functions• Intermediate Density Lipoprotein (IDL) – Synthesized from VLDL during VLDL degradation – Triglyceride transport and precursor to LDL – Apo B-100 • Receptor binding – Apo C-II • LPL activator – Apo E • Receptor binding
Plasma Lipoproteins Classes & Functions• Low Density Lipoprotein (LDL) – Synthesized from IDL – Half life of LDL in blood is 2 days – transport Cholesterol from liver to peripheral tissues – 75% of the plasma cholesterol is incorporated into the LDL particles are derived from VLDL, a small part is directly released from liver – 78% lipid (58% cholesterol & CE) – Apo B-100 • Receptor binding Interaction of LDL with LDL receptor
LDL Metabolism• LDL receptor-mediated endocytosis• About 75% of LDL are taken up by the liver, adrenal and adipose tissue cells by LDL receptor mediated endocytosis – LDL receptors on ‘coated pits’ • Clathrin: a protein polymer that stabilizes pit – Endocytosis • Loss of clathrin coating • uncoupling of receptor, returns to surface – Fusing of endosome with lysosome • Frees cholesterol & amino acids
Plasma Lipoproteins Classes & Functions• High Density Lipoprotein (HDL) – Synthesized in liver and intestine as protein rich discoid particles – Reservoir of apoproteins – Reverse cholesterol transport – 52% protein, 48% lipid, 35% C & CE – Apo A • Activates lecithin-cholesterol acyltransferase (LCAT) – Apo C • Activates LPL – Apo E • Remnant receptor binding
HDL Metabolism: Functions• Apoprotein exchange – provides apo C and apo E from VLDL and chylomicrons• Reverse cholesterol transport• Discoid HDLs are converted into spherical lipoprotein through the accumulation of cholesterol ester.
Reverse cholesterol transport• Uptake of cholesterol from peripheral tissues (binding by apo-A-I)• Esterification of HDL-C by LCAT – LCAT activated by apoA1• Transfer of CE to lipoprotein remnants (IDL and CR) by CETP• removal of CE-rich remnants by liver, converted to bile acids and excreted
Learning Objective 4• List the drug groups used in the treatment of hypercholesterolemia and identify members of each group.
• If a patient’s LDL cholesterol remains high, after changing diet and exercise habits, the doctor may prescribe medications to lower it.• If the patient’s cholesterol is very high (more than 200 mg/dL), they may start drug therapy at the same time they improve thier diet and exercise habits. Drugs commonly used to treat high cholesterol include: – Statins – Niacin (nicotinic acid) – Bile acid sequestrants – Cholesterol absorption inhibitors – Fibric acid derivatives
Statins• Statins are a class of medicines that are frequently used to lower blood cholesterol levels.• The drugs are able to block the action of a chemical in the liver that is necessary for making cholesterol.• Although cholesterol is necessary for normal cell and body function, very high levels of it can lead to atherosclerosis.• By reducing blood cholesterol levels, statins lower the risk of chest pain (angina), heart attack, and stroke.
How do statins work?• Statins inhibit an enzyme called HMG-CoA reductase, which controls cholesterol production in the liver.• The medicines actually act to replace the HMG-CoA that exists in the liver, thereby slowing down the cholesterol production process.
How do statins work?• Additional enzymes in the liver cell sense that cholesterol production has decreased and respond by creating a protein that leads to an increase in the production of LDL (low density lipoprotein, or "bad" cholesterol) receptors.
How do statins work?• These receptors relocate to the liver cell membranes and bind to passing LDL and VLDL (very low density lipoprotein).• The LDL and VLDL then enter the liver and are digested.
How do statins work?• Many people who begin statin treatment do so in order to lower their cholesterol level to less than 5 mmol/l, or by 25-30%.• The dosage may be increased if this target is not reached.• Treatment with the statin usually continues even after the target cholesterol level is reached in order to sustain atherosclerosis prevention.
Side-Effects of Statins• Although most people who take statins have minor or no side-effects, many suffer from – Headaches – Pins and needles – Abdominal pain – Bloating – Diarrhoea – Rashes – Rarely, patients get a severe form of muscle inflammation. – Avoid grapefruit juice
Niacin (nicotinic acid)• Niacin, also known as vitamin B3, is a water soluble vitamin comprised of nicotinic acid and niacinamide.• It is involved in the utilization of proteins, fats and carbohydrates, and is needed for energy production in the body.• It is necessary for the synthesis of fatty acids and the production of steroids.
Niacin (nicotinic acid)• Niacin can be synthesized in the body from tryptophan.• Niacin has been used since the 1950s for treatment of high cholesterol and other lipid abnormalities.• It modulates all fats and lipoproteins, and favorably alters their quality and quantity.• Niacin can be used alone or in combination with a cholesterol-lowering statin drug.
Mechanisms of Action• Niacin’s primary mechanism of action is to lower total cholesterol by reducing levels of low density lipoprotein (LDL), and very low density lipoprotein (VLDL).• Niacin lowers total cholesterol primarily by an inhibitory effect on triglyceride mobilization and synthesis, resulting in a reduction in blood levels of LDL and VLDL particles.• Even more benefit is conferred due to niacins ability to increase the particle size of LDL, rendering them less harmful to blood vessels.
Mechanisms of Action• In an article entitled, "The Effects of Niacin on Lipoprotein Subclass Distribution," by John M. Morgan, MD; Christina M. Carey, PA-C; Anne Lincoff, MD; and David M. Capuzzi, MD, PhD, the authors state that "niacin decreased the number of LDL particles by 15 percent at 1000 mg/d and by 23 percent at 2000 mg/d. Both dosages were also associated with significant increases in LDL particle size."• Niacin also has favorable effects on lipid profiles by increasing blood levels of HDL, the "good" cholesterol
Side-Effects of Niacin• Flushing (due to histamine release)• Pruritus• GI distress
Examples• Immediate-release form – Generic Name : niacin – Brand Name: Niacor• Sustained-release form – Generic Name : niacin – Brand Name: Slo-Niacin• Extended-release form – Generic Name: niacin – Brand Name: Niaspan
Bile acid sequestrants• Bile acid sequestrants, are a class of cholesterol lowering medications that work by binding to and preventing the absorption of cholesterol from the small intestine.• Instead of being absorbed into the blood, the combination of cholesterol and drug is excreted through the feces.
Bile acid sequestrants• Bile acid sequestrants mainly lower LDL cholesterol (“bad” cholesterol) by 15 to 30% and only slightly raise HDL cholesterol (“good” cholesterol) by 3 to 5%.• These drugs do not appear to affect triglyceride levels and, in some cases, bile acid sequestrants may actually raise your triglycerides if taken for a long period of time.
Mechanism Of Action• Bile acid sequestrants are polymeric compounds that serve as ion exchange resins.• Bile acid sequestrants exchange anions such as chloride ions for bile acids. By doing so, they bind bile acids and sequester them from enterohepatic circulation.• Since bile acid sequesterants are large polymeric structures, they are not well-absorbed from the gut into the bloodstream.• Thus, bile acid sequestrants, along with any bile acids bound to the drug, are excreted via the feces after passage through the gastrointestinal tract
Side Effects• Side effects consist of mainly gastrointestinal problems, such as flatulence, bloating, constipation, nausea, and bloating.• The side effects can be managed by increasing fluid intake or by adding fiber to your diet.• Additionally, bile acid resins may interact with some vitamins or other medications you are taking.
• Cholesterol absorption inhibitors -- The medication ezetimibe (Zetia) limits how much LDL cholesterol can be absorbed in the small intestine. Side effects include headaches, nausea, muscle weakness. Ezetimibe is combined with simvastatin in the drug Vytorin
• Fibric acid derivatives -- These medicines are effective at lowering triglyceride levels, and moderately effective at lowering LDL. They are used to treat high triglycerides and low HDL in people who cannot take niacin. Side effects include myositis, stomach upset, sun sensitivity, gallstones, irregular heartbeat, and liver damage.• Gemfibrozil (Lopid)• Fenofibrate (Tricor, Lofibra)
Learning Objective 5• Discuss the incidence and prevalence of ischaemic heart disease and hypertension in the Caribbean in relation to associated risk factors……NO
Learning Objective 6• Describe the process (identifying tasks) used to undertake research….JUST NOW
Learning Objective 7• Discuss the factors which influence what people eat (economic, social, ethnic, religious, educationa l).• I REAL GOOD