Lipid Metabolism Summary
• Since lipids cannot readily dissolve in blood plasma, they have to be
transported by being bound to a lipoprotein.
• Lipids absorbed from the GI tract are bound to a lipoprotein called a
chylomicron and enter into the lymph. The lymph drains into the subclavian
veins and the chylomicron can now circulate around the body in the blood.
• As the chylomicron passes through adipose tissue it releases some of its
triglycerides (TG) for storage. Once the chylomicron reaches the liver, it is
absorbed and broken-down into its components (i.e. TG, cholesterol,
vitamins)
• The liver is also responsible for producing cholesterol for the cells of the
body. Synthesized cholesterol, as well as cholesterol absorbed in the
chylomicron are packaged with TG into a very low-density lipoprotein (VLDL)
and released into the blood. As the VLDL passes through adipose tissue, it
releases some of its TG for storage. This converts the VLDL into a lowdensity lipoprotein (LDL).
• The LDL can now circulate around the body and deliver cholesterol to the
tissues, or can be taken-up by the liver and recycled. Occasionally,
macrophages can consume LDL, which can play a role in the
development of atherosclerosis.
Lipid Metabolism Summary Continued
• The liver also produces a high-density lipoprotein (HDL).
• HDL is released into the blood and is responsible for picking-up access
cholesterol from the tissues, and plays a scavenger role.
• The HDL ‘drops-off’
cholesterol at the liver and
is returned to the circulation.
The cholesterol removed by
the HDL is now excreted
from the body in the bile.
Porth Figure22-2:
Summary of Pathways for TG
and cholesterol transport and
metabolism
Atherogenesis: the “Response to Injury Theory”
• Although the exact mechanism of atherosclerosis development is not
known, it is believed to begin with endothelial damage and
inflammation (response-to-injury theory)
• The intima of an artery can become damaged from:
1. Mechanical stress (i.e. shear stress): high BP or high blood viscosity
2. Oxidative stress: certain metabolic processes result in the generation
of high levels of ROS e.g. LDL, diabetes, and smoking. ROS can
damage lipids, proteins, DNA and the intima of coronary arteries
• Damage to the endothelium then induces an inflammatory response;
damage also activates adhesion molecules and growth factors, and  Ang
II and ACE levels
– Inflammation leads to accumulation of macrophages which consume
LDL and become foam cells that form the initial fatty streak
– Ang II causes vasoconstriction (vasospasm) and reduced NO levels 
vascular smooth muscle proliferation, enhanced inflammation,
vasoconstriction and promotion of thrombosis. AngII also promotes
cardiac cell growth and can contribute to cardiac hypertrophy
Atherogenesis Cont’d
• Together, these factors lead to the formation of atherosclerotic lesions
(atheromas) which consist of foam cells, proliferating smooth muscle
cells, extracellular lipids, and firbrous tissue; thrombi easily form on
the lesions (See also Porth Figure 22-6)
Atherosclerotic
Plaque
Monocyte
Platelets
Injured
Endothelium
Blood
Foam
cells
Endothelium
Fibrous
Protein
Intima
Oxidized
LDL
Macrophage
Smooth
Muscle
J. Gordon
Atherogenesis Cont’d
• As the lesion growths it:
– occludes the lumen of the vessel
– may form a thrombus  complete
occlusion quickly
– weakens the BV wall, decreasing its
activity
– may calcify  further rigidity of the BV
wall
• These factors can lead to aneurysms,
Figure 18-11
rupture, or hemorrhage in the wall
Gould
• Recall: an emboli can break from the thrombus and cause occlusion of
other blood vessels, the most detrimental being cardiac, pulmonary and
cerebral
• Some plaques appear very stable for many years, whereas others may
progress very rapidly. Stability may be affected by the amount of lipid in
the plaque, as a plaque that contains lots of lipid may be very unstable,
may progress quickly, and may attract more macrophages and platelets. A
plaque with more fibrous tissue and little lipid will be more stable and less
likely to rupture, Thus decreasing predisposition to thrombosis
Atherosclerosis and Heart Disease
Porth: Chpts. 22, 24; Gould: Chpt 18
• Atherosclerosis is characterized by raised fibrofatty plaques
(atheromas) in the intimal lining of large and mediumsized blood vessels (blood vessels)
• Atherosclerosis is present in almost every human, and plaque
formation usually begins in the second decade of life
• This process is usually asymptomatic until a vessel is approximately
75% occluded. At this time the heart can show signs of ischemia (e.g.
angina), particularly during times of physical exertion
Anterior
The Coronary Arteries
• The myocardium receives blood from two
coronary arteries that branch from the base
of the aorta. These branches are called the
left and right coronary arteries.
• Left Main: The left coronary branches almost
immediately to form the left anterior
descending (LAD) and circumflex arteries.
Left Main
Right Main
Left Anterior
Descending
Marginal
Posterior
− The LAD (anterior interventricular) artery
supplies the anterior of both ventricles
and anterior septum
− The circumflex supplies the left atrium
and lateral and posterior left ventricle.
Circumflex
(1)
Circumflex
Right Main
Posterior
Descending
Anterior
The Coronary Arteries Cont’d
Left Main
• Right Main: The right coronary artery and
its branches (marginal and posterior
descending arteries) supply the anterior and
posterior right ventricle as well as the SA
and AV nodes.
Right Main
Marginal
Circumflex
Left Anterior
Descending
− Marginal: serves the myocardium of the
lateral right ventricle
(1)
− Posterior Descending: This artery
supplies the inferior and apex of the
myocardium and the posterior
ventricular walls. In most people the
posterior descending artery is a branch
of right main; however, it can branch
from the circumflex.
Circumflex
Right Main
Posterior
Descending
Coronary Blood Flow
• When the heart rate or metabolic rate increase (e.g. during exercise,
emotional stress, hyperthyroidism) smooth muscle in arterioles supplying the
heart muscle relaxes causing vasodilation and an increased blood flow. This
local dilation is caused by:
1) Metabolites produced by the heart muscle
2)  stimulation
3) Release of nitric oxide (NO) from the vascular endothelium
• The heart only receives blood during diastole: during systole the coronary
blood vessels are compressed, and the openings to the left and right
coronary arteries are partially blocked by the semilunar aortic valve
• Aortic blood pressure is the primary factor responsible for coronary perfusion
i.e. the heart influences its own blood supply
(11)
This is achieved in part by the ‘aortic recoil’
which aids cardiac perfusion through the
coronary arteries
• A high heart rate or other factors that decrease
the diastole time  cardiac perfusion time,
which may contribute to ischemia in an individual
with narrowed coronary arteries.
Coronary Blood Flow
• When the heart rate or metabolic rate increase (e.g. during exercise,
emotional stress, hyperthyroidism) smooth muscle in arterioles supplying the
heart muscle relaxes causing vasodilation and an increased blood flow. This
local dilation is caused by:
1) Metabolites produced by the heart muscle
2)  stimulation
3) Release of nitric oxide (NO) from the vascular endothelium
• The heart only receives blood during diastole: during systole the coronary
blood vessels are compressed, and the openings to the left and right
coronary arteries are partially blocked by the semilunar aortic valve
• Aortic blood pressure is the primary factor responsible for coronary perfusion
i.e. the heart influences its own blood supply
(11)
This is achieved in part by the ‘aortic recoil’
which aids cardiac perfusion through the
coronary arteries
• A high heart rate or other factors that decrease
the diastole time  cardiac perfusion time,
which may contribute to ischemia in an individual
with narrowed coronary arteries.
Metabolic Effects on Coronary Blood Flow
•  cardiac work and metabolism  coronary artery resistance and
hence  perfusion, and vice versa
Lumen of vessel
Arginine
NO
Relaxation
Adenosine, K+, H+, CO2, etc
Endothelial
cell
Blood
Vessel
Smooth
muscle
ISF
Heart muscle
• Coronary arteries possess beta-adrenergic receptors (dilators);
 activation  dilation of coronary arteries and  perfusion
Coronary Artery Disease (CAD)
Porth: Chpt. 24; Gould: Chpt. 18; Lewis: Chpt. 32
• CAD a.k.a:
– coronary heart disease (CHD)
– ischemic heart disease (IHD)
– cardiovascular heart disease (CVHD)
– arteriosclerotic heart disease (ASHD)
• CAD is the leading cause of death in North America
• CAD describe diseases caused by impaired coronary blood flow: can lead
to ischemia, infarction and cardiac arrest
Effects of Obstruction of the Coronary Arteries
• The heart extracts ~80% of O2 from coronary arterial blood with each
passage through the heart capillaries i.e. O2 supply to myocaridial cells is
flow limited;  O2 demand is met by  coronary artery blood flow
• Myocardial Ischemia  acidosis,  intracellular Na+ and Ca++, inhibition
of Na+/K+ pump  impaired contraction and necrosis
• Ischemia may by global or regional
• If occlusion of a coronary artery is gradual
and progressive, collateral circulation
develops to provide sufficient blood to the
ischemic region, thereby preventing or
limiting necrosis
• Abrupt occlusion  ischemic necrosis and
fibrosis
Figure 24-4 Porth
• Right coronary artery nourishes the AV node: obstruction  conduction
disturbances (arrhythmias)
• Left ventricle supplied by left coronary artery: obstruction  impaired
pumping (congestive heart failure)
Etiology of CAD
• The main cause of CAD is atherosclerosis
• Other less common causes include vasospasm, emboli, and congenital
coronary artery abnormalities
• Although the cause of atherosclerosis is unknown, there are a number of
risk factors that are generally considered modifiable or non-modifiable (be
able to categorize as either)
– Hypercholesterolemia (high LDL): greatest risk factor
– Age: men >45 years, women >55 years
– Family history of early CAD
– Genetic factors ~ serum lipid levels and metabolism
– Smoking, alcohol consumption
– Diabetes
– High BP
– Obesity
– Physical inactivity
– Stress
• The risk of developing CAD increases dramatically with multiple risk factors