2. Heart: Structure
• It is divided into 4 chambers: (Two upper &
Two lower)
• The two upper chambers are called
– Atria (Right & Left)
• The two lower chambers are called
– Ventricles (Right & Left)
• The two atria are separated by the
– Inter-Atrial Septum
• The two ventricles are separated by the
– Inter-Ventricular Septum
• The atrium and ventricle communicate with
each other via Atrioventricular orifice
3. Heart
Acts as a pump and has 4 chambers.
Upper two smaller chambers – Atrium
Lower two larger chambers – Ventricles
Volume of each chamber is the same
Ventricles are larger due to thicker walls.
Largest Chamber is the Left Ventricle which pumps blood all
over the body.
Thick wall between the Right and Left sides of heart –
Septum.
Blood -- Rt. Atrium -- Rt. Ventricle – Lungs -- Left Atrium -- Left Ventricle
4. Heart Interior
Rt Atrium
Rt Ventricle
Lt Ventricle
Lt Atrium
Septum
Heart is divided into 4
chambers where a
muscular wall or
Septum divides them
5. Circulatory System
• Heart
– Pumps blood
• Arteries and arterioles
– Carry blood away from heart
• Capillaries
– Exchange nutrients with tissues
• Veins and venules
– Carry blood toward heart
6. Heart Valves
• Heart valves act as gates between the heart chambers
• This orifice between atria and the ventricles is guarded
by
– A-V valve or the AtrioVentricular Valve
• They allow blood to pass between
– Heart chambers
– From heart chambers to their blood vessels
• They include the:
– Tricuspid
– Pulmonary
– Bicuspid (or mitral)
– Aortic valves
8. Cardiac Cycle
Sup Vena Cava brings
deoxygenated blood
from upper body to the
heart
Inf Vena Cava brings
deoxygenated blood
from lower body to the
heart
Pulmonary Artery
takes deoxygenated
blood to the lungs
Pulmonary Veins
brings oxygenated
blood from lungs
back to the Lt Atrium of
the heart
Aorta
takes blood to body
Blood from both veins is
received by Rt Atrium
and is pushed into the
R Ventricle RA
LA
RV
LV
SVC
IVC
Aorta
Pul A
Blood enters L
Ventricle from L Atrium
and is then pumped
into the Aorta
9. Cardiac Output - Q
• Q = HR x SV or Q = (FH) (Vs)
• Where:
• Q = volume of blood pumped by left ventricle
each minute (L.min)
• FH = heart rate (b/min)
• Vs = stroke volume (average volume of blood
pumped per each contraction (L/b)
10. Cardiac Output
• Range of normal at rest is 4 – 6 L.min
• During aerobic activity the increase in cardiac
output is roughly proportional to intensity.
• Max. Q is in range of 20 – 40 L.min, depending
on size, heredity, and conditioning.
11. Heart Rate
• Range of normal at rest
is 50 – 100 bpm
• Increases in proportion
to exercise intensity
• Max. HR is 220 – age
• Medications or upper
body exercise may
change normal response
12. Stroke Volume
• Range of normal at rest is 60 – 100 ml/b
• During exercise, SV increases quickly,
reaching max. around 40% of VO2 max.
• Max. SV is 120 – 200 ml/b, depending on size,
heredity, and conditioning.
• Increased SV during rhythmic aerobic exercise
is due to complete filling of ventricles during
diastole and/or complete emptying of
ventricles during systole.
13. Coronary Circulation
• Exclusive arterial blood supply
to heart muscle and electrical
conduction system originates
from the aorta
Aorta
Lt Coronary A
Lt Anterior
Descending Br
Rt Coronary A
14. Cardiac Cycle & Circulation
L Atrium
Aorta
L Ventricle
SVC
3. Capillary Bed
3. Arteriole4. Venule
Pul V
R Ventricle
R Atrium
IVC Pul A
2. Artery5. Vein
Oxygenation
Of blood in
the lungs
16. Major Arteries and Veins
• Aorta
• Pulmonary
• Carotid
• Femoral
• Brachial
• Radial
• Superior vena cava
• Inferior vena cava
• Pulmonary
• Jugular
17. Arterial Structure
Outer most layer: Adventitia
Made up of Collagen & Elastic fibres
Middle layer: Media
Made up of Smooth Muscle Cells
Innermost layer: Intima
Made up of Endothelial Cells
Lumen: Hollow
Blood: Cells & plasma etc
Longitudnal section
Cross Section
*Higher the Arterial resistance Higher will be the Afterload
18. Arteries: Physiological Effect
NORMAL STATE: (Results in)
• Smooth blood flow
• No risk of injury to artery
VASOCONSTRICTION: (Results in)
• Turbulent / fast blood flow
• High internal pressure
• High risk of injury to artery
VASODILATATION: (Results in)
• Slow blood flow
• Low internal pressure
• High risk for blood to escape circulation
Artery
Normal
Lumen
Dilated
Lumen
Narrow
Lumen
19. Capillaries
• Extremely narrow— 8-10 micrometer wide.
• One-cell thick walls composed mostly of epithelium
with a basement membrane
• Total surface area in humans is 6,000 m2
• Capillary beds present throughout body
• Oxygen and nutrients diffuse out of capillary into
tissue fluid that surrounds cells
• Wastes (CO2)diffuse into capillary
• Heart and vessels of CV system can be thought of
as means by which blood is conducted to and from
capillaries
• Each capillary bed has arteriovenous shunt
20.
21. Veins
• They arise from the organs
• They carry deoxygenated blood
– Exception: Pulmonary Vein which carries oxygenated blood
• They return blood from the tissues back to the heart
• They are thin walled vessels
• They do not have muscular or elastic walls
• They do not have the ability to:
• Contract: Vasoconstriction
• Dilate: Vasodilatation
• They are helped by valves and skeletal muscles in
returning blood back to the heart
23. Veins: Venous Return
B
Contracting
Skeletal
muscle
Applies
pressure on
vein and
squeazes it
to push
blood up
against
gravity
A
Relaxed
muscles
allow
Valves to
close up
and
prevent
the back
flow of
blood
under the
influence
of gravity
Gravity Gravity Gravity
Higher the Venous Return Higher will be the Preload
24. Pulmonary and Systemic Circulations
• Essentially two separate pumps:
– Right Side
• moves deoxygenated blood to the lungs for
oxygenation
– Left Side
• moves oxygenated blood to the body
• Which leads to two distinct
circulatory systems:
– Pulmonary
• vessels to and from the lungs
– Systemic
• vessels to and from the rest of the body
• Vessels that move blood away from
the heart are called arteries and
vessels that return blood to the heart
are called veins.
25. Systemic Circulation
• Each time the heart beats, a bolus (~ 80 mL) of blood
is ejected from the left ventricle into the aorta (the
largest artery).
• Blood flows into the medium-sized arteries and
arterioles (small muscular arteries) which branch off
the aorta.
• These vessels further subdivide into the capillaries
(smallest blood vessels that carry oxygenated blood).
26. • SA Node is called the pacemaker
• Keeps heartbeat regular
• If SA node fails to work properly, heart still beat due
to impulses generated by the AV node
• However, beat is slower
• To correct this situation, it is possible to implant an
artificial pacemaker
• Automatically gives an electrical stimulus to heart
every 0.85 seconds
Heart Conducting system
27. • SA node initiates heartbeat and automatically
sends out an excitation impulse every 0.85
second
• Causes atria to contract
• When impulses reach AV node, there is a
slight delay that allows atria to finish their
contraction before ventricles begin their
contraction
Heart Conducting system
28. • Signal for ventricles to contract travels from AV
node through two branches of AV bundle before
reaching numerous and smaller Purkinje fibers.
• The AV bundle, its branches, Purkinje fibers
consist of specialized muscle fibers that efficiently
cause ventricles to contract
Heart Conducting system
34. The story of lipids
• Chylomicrons transport fats from the intestinal
mucosa to the liver
• In the liver, the chylomicrons release
triglycerides and some cholesterol and become
low-density lipoproteins (LDL).
• LDL then carries fat and cholesterol to the
body’s cells.
• High-density lipoproteins (HDL) carry fat and
cholesterol back to the liver for excretion.
35. The story of lipids (cont.)
• When oxidized LDL cholesterol gets high,
atheroma formation in the walls of arteries
occurs, which causes atherosclerosis.
• HDL cholesterol is able to go and remove
cholesterol from the atheroma.
• Atherogenic cholesterol → LDL, VLDL, IDL
38. Atherosclerosis
Timeline
Stary et al. Circulation. 1995;92:1355-1374.
Foam
Cells
Fatty
Streak
Intermediate
Lesion Atheroma
Fibrous
Plaque
Complicated
Lesion/Rupture
Endothelial Dysfunction
From first decade From third decade From fourth decade
Growth mainly by lipid accumulation
Smooth muscle
and collagen
Thrombosis,
hematoma
43. Dietary sources of Cholesterol
Type of Fat Main Source Effect on
Cholesterol
levels
Monounsaturated Olives, olive oil, canola oil, peanut
oil, cashews, almonds, peanuts and
most other nuts; avocados
Lowers LDL,
Raises HDL
Polyunsaturated Corn, soybean, safflower and
cottonseed oil; fish
Lowers LDL,
Raises HDL
Saturated Whole milk, butter, cheese, and ice
cream; red meat; chocolate;
coconuts, coconut milk, coconut oil
, egg yolks, chicken skin
Raises both LDL
and HDL
Trans Most margarines; vegetable
shortening; partially hydrogenated
vegetable oil; deep-fried chips;
many fast foods; most commercial
baked goods
Raises LDL
44. Hereditary Causes of Hyperlipidemia
• Familial Hypercholesterolemia
• Codominant genetic disorder, coccurs in heterozygous form
• Occurs in 1 in 500 individuals
• Mutation in LDL receptor, resulting in elevated levels of LDL at
birth and throughout life
• High risk for atherosclerosis, tendon xanthomas (75% of
patients), tuberous xanthomas and xanthelasmas of eyes.
• Familial Combined Hyperlipidemia
• Autosomal dominant
• Increased secretions of VLDLs
• Dysbetalipoproteinemia
• Affects 1 in 10,000
• Results in apo E2, a binding-defective form of apoE (which
usually plays important role in catabolism of chylomicron and
VLDL)
• Increased risk for atherosclerosis, peripheral vascular disease
• Tuberous xanthomas, striae palmaris
45. Hyperlipidaemias
There are 6 types of hyperlipidemia which
are differentiated by the type(s) of lipids
that are elevated in the blood.
Some of the types may be due to a primary
disorder such as a familial hyperlipidemia,
and some are due to secondary causes.
Secondary causes of hyperlipidemia are
related to diseases associated with
hyperlipidemia, dietary risk factors, and
drugs associated with hyperlipidemia.
46. Type I IIa IIb III IV V
Lipids
Cholesterol N, > >> >> N, >> N, > N, >>
Triglycerides >> N >> N, >> >> >>
Lipoproteins
Chylomicrons >> N N N N >>
VLDL N, > N, << << N, > >> >>
ILDL >>
LDL << >> >> >> N, < <<
HDL << N N N N, < <<
Treatment Diet
Diet, Statins, Bile
Acid
Sequestrants, Nicoti
nic Acid
Diet, Statins,
Bile Acid
Sequestrants,
Fibrates,
Nicotinic Acid
Diet, Fibrates,
Nicotinic Acid
Diet, Fibrates,
Nicotinic Acid
Diet, Fibrates,
Nicotinic Acid
47. Lipid Parameter Function:
Latest Commentary
VLDL
Carries triglycerides to peripheral cells
High levels may be associated with increased CHD risk2
LDL
Carries cholesterol to cells
High levels linked to increased CHD risk
Primary target of cholesterol-reducing therapy3
HDL
Removes cholesterol from cells
High HDL considered protective against CHD
HDL >60 mg/dL decreases CHD risk1
Lipoprotein(a)
A complex of LDL and apolipoprotein(a)
Prevents LDL from being taken up by the Liver
Elevated Lp(a) is an independent risk factor for premature CHD4
Triglycerides
A neutral fat stored in adipose cells
Positively correlated with risk for CHD1
48. Clinical Manifestations
of Atherosclerosis
• Coronary heart disease
– Stable angina, acute myocardial infarction, sudden
death, unstable angina
• Cerebrovascular disease
– Stroke, TIAs
• Peripheral arterial disease
– Intermittent claudication, increased risk of death
from heart attack and stroke
American Heart Association, 2000.
49. Risk Factors for CHD
• Modifiable
– Dyslipidemia
Raised LDL
Low HDL
Raised TGs
– Smoking
– Hypertension
– Diabetes mellitus
– Obesity
– Dietary factors
– Thrombogenic
factors
– Sedentary lifestyle
Wood D, et al. Atherosclerosis. 1998;140:199-270.
• Nonmodifiable
– Age
– Sex
– Family history of
premature CHD
50. DYSLIPIDEMIA
(A consequence of abnormal lipoprotein metabolism)
• Elevated Total Cholesterol (TC)
• Elevated Low-density lipoproteins (LDL)
• Elevated triglycerides (TG)
• Decreased High-density lipoproteins (HDL)
51. PRIMARY DYSLIPIDEMIA
ETIOLOGY
• SINGLE OR MULTIPLE GENE MUTATION –
RESULTING IN DISTURBANCE OF LDL, HDL AND
TRIGYLCERIDE, PRODUCTION OR CLEARANCE.
• Should be suspected in patients with
– premature heart disease
– family hx of atherosclerotic dx.
– Or serum cholesterol level >240mg/dl.
– Physical signs of hyperlipidemia.
52. SECONDARY DYSLIPIDEMIA
(Most adult cases of dyslipidemia are secondary in nature in western
civilizations)
• Sedentary lifestyle
• Excessive consumption of cholesterol –
saturated fats and trans-fatty acids.
55. Why Do We Care?
According to the Third Report of
the National Cholesterol
Education Program Expert
Panel on Detection, Evaluation
and Treatment of High
Cholesterol in Adults
(NCEP ATP-III):
High LDL levels are a leading
cause of coronary heart
disease (CHD) and should be
the main target of any
cholesterol lowering regimen
56. Checking lipids
• Nonfasting lipid panel
• measures HDL and total cholesterol
• Fasting lipid panel
• Measures HDL, total cholesterol and
triglycerides
• LDL cholesterol is calculated:
– LDL cholesterol = total cholesterol – (HDL +
triglycerides/5)
57. LDL Cholesterol
• Remains the cornerstone of dyslipidemia therapy1
• Strongly associated with atherosclerosis and
CHD events1
• 10% increase results in a 20% increase in
CHD risk1
• Most patients with elevated LDL untreated
– Only 4.5 million out of 28.4 million treated2,3
1. Wood D et al. Atherosclerosis. 1998;140:199-270.
2. National Centre for Health Statistics. National Health and Nutrition
Examination Survey (III), 1994.
3. Jacobson TA, et al. Arch Intern Med. 2000;160:1361-1369.
58. HDL Cholesterol
• Low HDL cholesterol is a strong independent
predictor of CHD1
• The lower the HDL cholesterol level the higher
the risk for atherosclerosis and CHD2
• Low HDL is defined categorically as a level < 40
mg/dL (a change from < 35 mg/dL in ATP II)1
• HDL cholesterol tends to be low when
triglycerides are high2
1. NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
2. Wood D, et al. Atherosclerosis. 1998;140:199-270.
59. Triglycerides
• Recent data suggest that elevated triglycerides
are an independent risk factor for CHD
• Normal triglyceride levels: < 150 mg/dL
• Borderline-high triglycerides: 150 to 199 mg/dL
• High triglycerides: 200 to 499 mg/dL
• Very high triglycerides: ( 500 mg/dL) increase
pancreatitis risk
– Initial aim of therapy is prevention of acute
pancreatitis
NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
60. Non-HDL Cholesterol
• Non-HDL Cholesterol = TC – HDL Cholesterol1
• Secondary target of therapy when serum TG
200 mg/dL1
• New non-HDL-C goal for patients with elevated
TG is LDL-C goal + 30 mg/dL1
• Non-HDL-C includes all atherogenic lipoprotein
particles including LDL-C, Lp(a), IDL-C, and
VLDL-C2
1. NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
2. Cui Y, et al. Arch Intern Med. 2001;161:1413-1419.
61. National Cholesterol Education Program, Adult
Treatment Panel III (NCEP ATP III)
• The National Cholesterol Education Program’s
updated clinical guidelines for cholesterol testing
and management announced in May 2001
• Establishes goals for patients with varying levels
of risk
• ATP III builds on previous ATP reports and
expands the indications for intensive cholesterol-
lowering therapy
NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
62. New Concepts for ATP III
Modified Risk Factor Assessment
• Inclusion of more patients in the high-risk category
(greater focus on diabetes, noncoronary
atherosclerosis, multiple risk factors)
• Incorporation of global risk assessment in the
guidelines
• Complete fasting lipoprotein profile recommended
• Definition of low HDL-C is now < 40 mg/dL for
males and females
• Triglyceride cut points lowered from 200 mg/dL to
150 mg/dL
NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
63. New Concepts for ATP III (cont)
Modified Treatment Guidelines
• LDL-C < 100 mg/dL identified as optimal
• LDL-C goal of < 100 mg/dL expanded to include CHD
patients and those with CHD risk equivalent
NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
64. New Concepts for ATP III (cont)
More Intensive Lifestyle Intervention:
Therapeutic Lifestyle Changes (TLC)
• Therapeutic diet lowers saturated fat (< 7% of total
calories) and cholesterol (< 200 mg/d) intakes to levels of
previous Step II diet
• Adds dietary options to enhance LDL-C lowering
– Plant stanols/sterols (2 g/d)
– Viscous (soluble) fiber (10-25 g/d)
• Increased emphasis on weight management and physical
activity
NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
65. LDL Cholesterol Goals for Therapeutic Lifestyle
Changes (TLC) and Drug Therapy According to
NCEP ATP III
Risk Category
LDL-C Goal
(mg/dL)
LDL-C Level for
Initiation of TLC
(mg/dL)
LDL-C Level for
Consideration of
Drug Therapy
(mg/dL)
CHD or CHD
Risk Equivalents
(10-y risk > 20%)
2 + Risk Factors
(10-y risk 20%)
0-1 Risk Factor
< 100
< 130
< 160
100
130
160
130
(100-129: drug optional)
10-y risk 10%-20%: 130
10-y risk < 10%: 160
190
(160-189: LDL-C-lowering
drug optional)
NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
67. LDL Cholesterol Goals and Cutpoints for
Therapeutic Lifestyle Changes (TLC)
and Drug Therapy in Different Risk Categories
Risk Category
LDL Goal
(mg/dL)
LDL Level at Which
to Initiate
Therapeutic
Lifestyle Changes
(TLC) (mg/dL)
LDL Level at Which
to Consider
Drug Therapy
(mg/dL)
CHD or CHD Risk
Equivalents
(10-year risk >20%)
<100 100
130
(100–129: drug
optional)
2+ Risk Factors
(10-year risk 20%)
<130 130
10-year risk 10–
20%: 130
10-year risk <10%:
160
0–1 Risk Factor <160 160
190
(160–189: LDL-
lowering drug
optional)
68. LDL Cholesterol Goal and Cutpoints for
Therapeutic Lifestyle Changes (TLC) and Drug
Therapy in Patients with CHD and CHD
Risk Equivalents (10-Year Risk >20%)
130 mg/dL
(100–129 mg/dL:
drug optional)
100 mg/dL<100 mg/dL
LDL Level at Which
to Consider Drug
Therapy
LDL Level at Which
to Initiate
Therapeutic Lifestyle
Changes (TLC)
LDL Goal
69. LDL Cholesterol Goal and Cutpoints for
Therapeutic Lifestyle Changes (TLC) and Drug
Therapy in Patients with Multiple Risk Factors
(10-Year Risk 20%)
LDL Goal
LDL Level at
Which to Initiate
Therapeutic
Lifestyle Changes
(TLC)
LDL Level at
Which to
Consider Drug
Therapy
<130 mg/dL 130 mg/dL
10-year risk 10–
20%: 130 mg/dL
10-year risk
<10%:
160 mg/dL
70. LDL Cholesterol Goal and Cutpoints for
Therapeutic Lifestyle Changes (TLC) and Drug
Therapy in Patients with 0–1 Risk Factor
190 mg/dL
(160–189 mg/dL:
LDL-lowering drug
optional)
160 mg/dL<160 mg/dL
LDL Level at Which to
Consider Drug
Therapy
LDL Level at Which to
Initiate Therapeutic
Lifestyle Changes
(TLC)LDL Goal
