1. MDSC 1102 PBL PROBLEM 4
BY ARVIND SEECHARAN
(FUTURE DOCTOR EXTRAORDINAIRE)

2. Learning Objective 1
• Discuss the blood supply and venous and
lymphatic drainage of the heart

3. Blood supply of heart
Arterial supply:
• Heart is supplied by right and left coronary
arteries
• These surround the heart like an inverted
crown

4. Heart (sternocostal surface)
Ascending aorta
Right auricle
Left coronary artery
Right
coronary
artery Circumflex artery
Anterior
interventricular
artery
Right marginal Great cardiac
artery vein
Pulmonary trunk

5. Heart (base and diaphragmatic surface)
Left atrium
Right atrium
Circumflex
artery
Right coronary
artery
Left ventricle Right ventricle

6. • 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

7. Branches of right coronary artery
• Right conus artery
• Atrial branches
• Ventricular
branches
• Right marginal
artery
Atrial • Posterior
branch
interventricular
artery
Right
marginal Right
artery conus Ventricular
artery branch

8. • 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

9. • 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

10. • 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

11. Heart (sternocostal surface)
Ascending aorta
Left coronary artery
Right
coronary
artery Circumflex artery
Anterior
interventricular
artery
Great cardiac
vein
Pulmonary trunk

12. Heart (base and diaphragmatic surface)
Left atrium
Right atrium
Circumflex
artery
Right coronary
artery
Posterior inter-
ventricular artery
Left ventricle Right ventricle

13. • 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

14. • 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

15. • 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

16. • 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

17. Coronary sinus and its tributaries
Left atrium
Oblique vein
of left atrium
Right atrium
Great cardiac vein
Coronary sinus
Small cardiac vein
Posterior vein of
left ventricle
Left ventricle Right ventricle Middle cardiac vein

18. • 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

19. • 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

20. • Thebasian veins (venae cordis minimae):
• Small veins situated in the myocardium of all the
chambers
• Terminate by opening into all chambers

21. 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.

22. 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

24. 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

25. 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).

26. 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

27. • 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.

28. • 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.

29. • 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.

30. 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.

31. 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.

32. 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

33. 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.

34. 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.

35. 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

36. Age
• Age (increasing) can increase the incidence of
cardiac diseases especially among women.

37. 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.

38. 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.

39. • 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

40. Learning Objective 3
• Discuss the biochemistry of plasma
lipoproteins and the risks associated with an
abnormal lipid profile.

41. Lipoprotein Structure and Function
Are conjugated proteins, composed of core and surface
• LP core
– Triglycerides
– Cholesterol esters
• LP surface
– Phospholipids
– Proteins
– Cholesterol

42. • 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.

43. Composition and characteristics

44. 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).

45. Separation by Electrophoresis
 Based on difference in their mobilization in an electric field

46. Plasma Lipoproteins Classes & Functions
Chylomicrons
– 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

47. 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

48. • 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

49. 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

50. 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

51. 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

52. 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

53. 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

54. 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

55. 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.

56. 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

57. Learning Objective 4
• List the drug groups used in the treatment of
hypercholesterolemia and identify members
of each group.

58. • 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

59. 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.

60. 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.

61. 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.

62. 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.

63. 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.

64. 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

65. Examples of Statins
• Lovastatin (Mevachor)
• Pravastatin (Pravachol)
• Rosuvastatin (Crestor)
• Simvastatin (Zocor)
• Atorvastatin (Lipitor)
• Fluvastatin (Lescor)

66. 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.

67. 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.

68. 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 niacin's ability to
increase the particle size of LDL, rendering them less
harmful to blood vessels.

69. 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

70. Side-Effects of Niacin
• Flushing (due to histamine release)
• Pruritus
• GI distress

71. 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

72. 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.

73. 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.

74. 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

75. 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.

76. Examples
• Cholestyramine (Prevalite, Questran)
• Colestipol (Colestid)
• Colesevelam (WelChol)

77. • 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

78. • 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)

79. Learning Objective 5
• Discuss the incidence and prevalence of
ischaemic heart disease and hypertension in
the Caribbean in relation to associated risk
factors……NO

80. Learning Objective 6
• Describe the process (identifying tasks) used
to undertake research….JUST NOW

81. Learning Objective 7
• Discuss the factors which influence what
people eat
(economic, social, ethnic, religious, educationa
l).
• I REAL GOOD