Transcript Serum Lipid Transport - William M. Clark, M.D

Transfer of Lipids
Mike Clark, M.D.
Cholesterol
Recommended Daily Diet
• 45% – 65% of daily kilocalories Carbohydrates
(most being complex carbohydrates)
• 20% - 35% of daily kilocalories from *Fats
• 10 – 35% of daily kilocalories from Protein
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Thus on a 2,000 kilocalorie diet you should get
Total Carbohydrates --- 300 grams with at least
25 grams being fiber
Total fat --- 65 grams or less
Total Protein -- 50 grams
Next slide breaks down fats
• Cholesterol in the body (1) comes from the diet (2)
recycled within the body through reabsorption of bile
in the digestive tract or (3) synthesized in the body.
• For a person of about 70 Kg. person typical total body
cholesterol content is about 35 g, with typical daily
dietary intake is 200–300 mg in (United States) and
approximately 1 gram produced daily by the body.
Daily Recommendations
total fat: less than 65 g
saturated fat: less than 20 g
cholesterol: less than 300 mg (milligrams)
sodium: less than 2,400 mg
Potassium: 3,500 mg
Function of Cholesterol
1. Cholesterol is required to build and maintain cell
membranes; it regulates membrane fluidity over the
range of physiological temperatures.
2. Within the cell membrane, cholesterol also functions in
intracellular transport, cell signalling and nerve
conduction.
3. Recently, cholesterol has also been implicated in cell
signaling processes, assisting in the formation of lipid rafts
in the plasma membrane. In many neurons a myelin
sheath, rich in cholesterol since it is derived from
compacted layers of
4. Cholesterol is an important precursor molecule for the
synthesis of Vitamin D and the steroid hormones,
including the adrenal gland hormones cortisol and
aldosterone as well as the sex hormones progesterone,
estrogens, and testosterone and their derivatives.
Cholesterol Structure
Cholesterol is a sterol type steroid - are also known as
steroid alcohol. When a steroid has an OH (hydroxyl)
group at the 3-position of the A-ring – it is termed a
sterol.
What is a Cholesterol Ester?
• A cholesteryl ester is, as its name would
imply, an ester of cholesterol. The ester bond
is formed between the carboxylate group of a
fatty acid and the hydroxyl group (on 3rd
carbon) of cholesterol. Cholesteryl Esters have
a lower solubility in water than Cholesterol.
They are associated with atherosclerosis
Cholesterol Ester
Dietary sources
• Animal fats are complex mixtures of triglycerides,
with lesser amounts of phospholipids and
cholesterol. Consequently all foods containing
animal fat contain cholesterol to varying extents.
Major dietary sources of cholesterol include
cheese, egg yolks, beef, pork, poultry, and
shrimp. Human breast milk also contains
significant quantities of cholesterol. Cholesterol is
not present in plant based food sources unless it
has been added during the food's preparation.
However, plant products such as flax seeds and
peanuts contain healthy cholesterol-like
compounds called phytosterols, which are
suggested to help lower serum cholesterol levels.
Synthesis
• About 20–25% of total daily cholesterol
production occurs in the liver; other sites of
high synthesis rates include the intestines,
adrenal glands and reproductive organs.
• Synthesis within the body starts with one
molecule of acetyl CoA and one molecule of
acetoacetyl. HMG-CoA reductase is an
important enzyme in Cholesterol Production
– this is the enzyme targeted by the Statin
(HMG-CoA Reductase Inhibitors) drugs.
Regulation of cholesterol synthesis
• Biosynthesis of cholesterol is directly
regulated by the cholesterol levels present,
though the homeostatic mechanisms involved
are only partly understood. A higher intake
from food leads to a net decrease in
endogenous production, while lower intake
from food has the opposite effect.
Plasma transport and regulation of absorption
• Cholesterol is only slightly soluble in water; it can
dissolve and travel in the water-based bloodstream at
exceedingly small concentrations. Since cholesterol is
insoluble in blood, it is transported in the circulatory
system within lipoproteins.
• Cholesterol since it has the polar hydroxyl group is
slightly soluble in water – but the esterified form is less
soluble in water. It is more able to be packaged into
small areas for transport and storage.
Cholesterol esters, i.e. with long-chain fatty acids linked
to the hydroxyl group, are much less polar than free
cholesterol and appear to be the preferred form for
transport in plasma and for storage. They do not
contribute to membranes but are packed into
intracellular lipid particles.
Metabolism, recycling and excretion
• Cholesterol is oxidized by the liver into a variety of primary bile
acids. These primary bile acids are “ cholic acid” and
chenodeoxycholic acid. When these primary bile acids are
secreted into the intestines in bile - bacteria in the large
intestines converts some these into secondary bile acids –
deoxycholic acid (from cholic acid) and lithocholic acid (from
chenodeoxycholic acid). Bacteria also did this to bilirubin.
• In the liver some of the primary bile acids are conjugated
(covalently bonded to primarily glycine and taurine – making
them more water soluble- just as bilirubin was conjugated to
make it more water soluble. When the primary bile acids are
conjugated they are called bile salts – then named glycocholic
acid and taurocholic acid. Thus a mixture of conjugated and
non-conjugated bile acids along with cholesterol itself is
excreted from the liver into the bile.
• Approximately 95% of the bile acids are reabsorbed from the
intestines and the remainder lost in the feces. The excretion and
reabsorption of bile acids forms the basis of the enterohepatic
circulation. which is essential for the digestion and absorption
of dietary fats.
Serum Lipid Transport
• Some lipids come from diet
(exogenous)
• Some lipids are produced by the
body (endogenously)
Lipids
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Fatty Acids
Triglycerides
Phospholipids
Steroids
Carotenoids
Eicosanoids
Fat Soluble Vitamins
Serum Lipids involved in metabolism
that need assistance with transport in the blood
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Fatty Acids
Triglycerides
Cholesterol
Fat Soluble Vitamins
Help with the transport involves usage of
proteins and phospholipids
• NOTE: Anything that is lipid soluble or highly
oxidative (Iron) also need transport assistance
in the blood like lipid hormones (cortisol)
General Lipoprotein Structure
• A core consisting of hydrophobic substances –
cholesterol esters and Triglycerides
• Surrounding the core are amphipathic and
hydrophilic substances – unesterified
cholesterol, phospholipids and proteins
• The density of the lipoprotein depends on the
relative percentage of protein – more protein
more dense.
Lipoprotein Structure
Apoprotein
POLAR
SURFACE COAT
Phospholipid
Free cholesterol
Apoprotein
NONPOLAR
LIPID CORE
Cholesterol Ester
Triglyceride
Apoprotein
Adapted from Treatment of Heart Diseases :1992, Etiologies and Treatment of Hyperlipidemia-Scott Grundy, MD, PhD
Phospholipid responsibility
Since they are amphipathic – they give the
hydrophobic lipids increased water solubilityemulsification
Protein responsibility
• The proteins are termed apolipoproteins.
• Responsible for activating certain enzymes in
metabolism and as attachments of the
lipoprotein to the cell membranes (ligand)
Micelle
• Not a lipoprotein but involved in exogenous
lipid metabolism
• Need to get lipids in intestine underneath the
water layer so that these lipids can get to the
top of the intestinal epithelial cells for
absorption – thus need to form a “micelle”
• This process involves making lipids soluble in
water “emulsification”
• Bile assists in this function
Bile Composition
• Remember bile is formed in the liver and stored in the gallbladder
its function is to solubilize (emulsify) fats in the small intestines
• Water – when stored in gallbladder considerable water is removed
from the bile so as to make it more concentrated thus easier to
store.
• Unesterified Cholesterol
• Bile pigments (Bilirubin)
• Bile salts (glycocholic acid & taurocholic acid)
• Bile acids – primary – cholic acid and chenodeoxycholic acid
• Bile acids – secondary – deoxycholic acid and lithocholic acid
• Phospholipids (mainly lecithin) Dipalmitoyl phosphatidyl choline
• Electrolytes
• Bicarbonate
Micelle
Microvilli
(brush border)
Absorptive cells
Lacteal
Goblet cell
Blood
capillaries
Mucosa
associated
lymphoid tissue
Intestinal crypt
Muscularis
mucosae
Duodenal gland
(b)
Vilus
Enteroendocrine
cells
Venule
Lymphatic vessel
Submucosa
Figure 23.22b
Serum Lipids
needing assistance with transport in the blood
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Fatty Acids
Triglycerides
Fat Soluble Vitamins
Cholesterol
• Help with the transport involves usage of
proteins and phospholipids
Transporting Lipoproteins
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Chylomicron
Very Low Density Lipoprotein (VLDL)
Low Density Lipoprotein (LDL)
Intermediate Density Lipoprotein (IDL)
High Density Lipoprotein (HDL)
Chylomicron
80% – 95% Triglyceride
2% - 7% Cholesterol
3%-6% Phospholipid
1% – 2% Proteins
Function
• Chylomicrons transport exogenous lipids to liver, adipose, cardiac
and skeletal muscle tissue where their triglyceride components are
unloaded by the activity of lipoprotein lipase. Consequently,
chylomicron remnants are left over and are taken up by the liver.
• Stages
• There are three stages in the chylomicrons "life cycle":
• Nascent chylomicron
• Mature chylomicron - after HDL gives it some apoproteins
• Chylomicron remnant – after some triglycerides removed
Nascent (newly formed) chylomicrons in small intestine epithelial cells
Chylomicrons are created by the absorptive cells of the small intestine. They
are relatively large, having a diameter of 75 to 1,200nm. These nascent
chylomicrons are released by exocytosis from enterocytes into lacteals,
lymphatic vessels originating in the villi of the small intestine, and are then
secreted into the bloodstream at the thoracic duct's connection with the
left subclavian vein.
Nascent chylomicrons are primarily composed of triglycerides (85%) and
contain some cholesterol and cholesteryl esters. The main apolipoprotein
component is apolipoprotein B-48 (APOB48).
Mature chylomicron (after acted upon by HDL)
While circulating in lymph and blood, chylomicrons exchange components
with high-density lipoproteins (HDL). The HDL donates apolipoprotein C-II
(APOC2) and apolipoprotein E (APOE) to the nascent chylomicron and thus
converts it to a mature chylomicron (often referred to simply as
"chylomicron"). APOC2 is the cofactor for lipoprotein lipase (LPL) activity.
Chylomicron remnant (after has loss considerable amounts of triglycerides
Once triglyceride stores are distributed, the chylomicron returns APOC2 to
the HDL (but keeps APOE) and thus becomes a chylomicron remnant, now
only 30 - 50 nm. APOB48 and APOE are important to identify the
chylomicron remnant in the liver for endocytosis and breakdown.
VLDL (mainly carries triglycerides)
55% – 65% Triglyceride
10% - 15% Cholesterol
15%-20% Phospholipid
5% – 10% Proteins
• Very low-density lipoprotein (VLDL) is a type
of lipoprotein made by the liver.
• VLDL transports endogenous products whereas
chylomicrons transport exogenous (dietary) products.
• VLDL transports endogenous triglycerides,
phospholipids, cholesterol and cholesteryl esters. It
functions as the body's internal transport mechanism
for lipids
Changes during circulation
• Nascent VLDL circulates in blood and picks up apolipoprotein C-II
and apolipoprotein E donated from High-Density Lipoprotein (HDL).
At this point, the nascent VLDL becomes a mature VLDL. Once in
circulation, the VLDL will come in contact with lipoprotein lipase
(LPL) in the capillary beds in the body (adipose, cardiac, and skeletal
muscle). The LPL will remove triglycerides from the VLDL for storage
or energy production.
• The VLDL now meets back up with HDL where apoC-II is transferred
back to the HDL (but keeps apoE). In addition to this, the HDL
transfers cholesteryl esters to the VLDL in exchange for
phospholipids and triglycerides (via cholesteryl ester transfer
protein).
• As more and more triglycerides are removed from the VLDL
because of the action of the LPL enzyme, the composition of the
molecule changes, and it becomes intermediate density
lipoprotein (IDL).
Intermediate Density Lipoprotein (IDL)
(transient role has equal amounts of cholesterol and triglycerides)
• 50% of IDLs are recognized by receptors in the
liver cells (because of the apoB-100 and apoE
they contain) and are endocytosed.
• The other 50% of IDL lose their apoE. When
their cholesterol content becomes greater
than the triglyceride content, they become
low-density lipoprotein (LDL), with the
primary apolipoprotein being apoB-100.
Low Density Lipoprotein (primarily carries cholesterol)
sometimes referred to as your “Bad Cholesterol”
10% Triglyceride
45 % Cholesterol
20% Phospholipid
25% Proteins
• Low-density lipoprotein (LDL) is a type of lipoprotein that
transports cholesterol and triglycerides from the liver to peripheral
tissues.
• When a cell requires cholesterol, it synthesizes the necessary LDL
receptors, and inserts them into the plasma membrane. The LDL
receptors diffuse freely until they associate with clathrin-coated
pits. LDL particles in the blood stream bind to these extracellular
LDL receptors. The clathrin-coated pits then form vesicles that are
endocytosed into the cell.
• The LDL is taken into a cell via the LDL receptor (endocytosis) where
the contents are either stored, used for cell membrane structure, or
converted into other products (steroid hormones or bile acids).
High Density Lipoprotein (HDL)
(scavenges extra cholesterol taking to the liver)
sometimes called your “Good Cholesterol”
5% Triglyceride 30 % Phospholipid
20% Cholesterol
45% – 55% Proteins
• HDL is produced by the liver
• Function is to scoop up and transport excess
cholesterol from peripheral tissues to the liver
• Provides apolipoproteins to Chylomicrons,
VLDL and LDL
Complete Story
1. Eat meal with cholesterol, triglycerides, fatty acids
and fat soluble vitamins
2. Triglycerides are broken down to a monoglyceride and
two fatty acids by pancreatic lipase (some salivary and
gastric) – all other lipids stay as they are
3. In order to absorb lipids need bile to emulsify the
lipids so as to allow them to pass below the water
layer lining the intestines– bile enters first part of
intestines (Duodenum) from hepatopancreatic duct –
same duct that allowed the pancreatic lipase into the
intestines.
4. Bile mixes with lipids forming a micelle
5. The Micelle allows the fat to move to the top of the
intestinal epithelial cells
Triglyceride
Figure 23.36
6. The lipids are allowed into the intestinal epithelial cells
by simple diffusion – particularly at the ileum (last part
of small intestine)
7. The bile forming the micelle will stay behind and some
is absorbed later in the small intestine and large
intestines (enterohepatic circulation) and some is
eliminated in the feces. Remember in the large
intestines, normal flora bacteria convert some of the
primary acids in bile to secondary acids and half of
the bilirubin was converted to urobilinogen (lecture
given earlier on bilirubin).
8. Once the fats are in the in the intestinal epithelial cells
– the monoglycerides are reunited to form
triglycerides and all of the lipids are packaged into the
chylomicrons.
Figure 23.20
9. The chylomicrons are too large to diffuse through the epithelial cell
membrane or the through the basement membrane so they are
extruded by exocytosis.
10. The chylomicrons then enter the central lacteal of the lymphatics
and the lymphatics carry them to the bloodstream at the Thoracic
Duct.
11. Once in the bloodstream capillary endothelial cells in skeletal
muscle, cardiac muscle and adipose tissue– produce and secrete
“lipoprotein lipase” – this causes the chylomicron to hydrolyze the
triglycerides ( to breakdown to glycerol and 3 fatty acids) these are
absorbed into the myocytes and adipocytes. Some fatty acids are
whisked away by albumin to go to other cells in particular the liver
cells. When the Chylomicron releases some of its triglycerides and
HDL takes its cholesterol and apolipoproteins becomes a
Chylomicron Remnant.
12. The Chylomicron remnant enters the liver cells by endocytosis for
breakdown – thus the remaining triglycerides along with the
absorbed cholesterol are now in the liver for storage or
subsequent transport.
Figure 23.21b, c
13. The liver stores some of the lipids and some it sends out by
forming VLDL. This is high in Triglycerides (55%- 65%) and
somewhat lower in cholesterol (10% -15%).
14. The VLDL then circulates until it is met by lipoprotein lipase
in the capillary endothelial cells of adipose tissue (need
insulin) , cardiac muscle and skeletal muscle. Lipoprotein
Lipase as before causes triglycerides to dissolve and be
absorbed by the mentioned cells. This then increases the
density of the lipoprotein forming IDL (Intermediate Density
Lipoprotein).
15. Some (50%) of IDL is taken up by the liver and
broken down – the other 50% loses more
triglycerides thus increasing the relative density of
the lipoprotein and the amount of cholesterol –
until finally becoming LDL (Low Density
Lipoprotein).
16. Low Density Lipoprotein primarily carries Cholesterol
(45%). It circulates until it is bound to LDL receptors.
Every cell in the body forms LDL receptors in that every
cell in the body needs cholesterol. Some cells such as
those forming the steroid hormones need more receptors.
The amount of receptors placed in the cell membrane is
under the control of homeostasis. The liver generally
sports lots of LDL receptors thus clearing about 70% of
LDL. The liver does to store cholesterol and decrease the
amount of cholesterol in the circulation – thus minimizing
atherosclerosis.
17. LDL and its lipid contents are taken into cells by receptor
mediated endocytosis and broken down. The cell that
performed the endocytosis uses the lipids for its own
purposes. However – the cholesterol in the liver is stored
so as to be transported to cells that need cholesterol – by
forming VLDL again – thus the story starts again.
18. HDL is not part of the conversion process of
VLDL to IDL to LDL. It is produced
independently primarily by the liver and some
by intestinal cells
• It functions to scoop up and transport excess
cholesterol from peripheral tissues to the
liver- thus scavenging the excess cholesterol
“Good Cholesterol”
• It also provides apolipoproteins to
Chylomicrons and VLDL – thus enhancing their
efforts to keep excess triglycerides out of the
circulation
Desired Blood Lipid Levels
Desirable
Borderline High
High
Cholesterol (Adult) < 200 mg/dl
200 - 239
>240
LDL
< 130
130 -159
> 160
HDL
> 45
TC/HDL ratio
<4.5
Triglycerides
< 150
What drugs are most commonly used to treat
high cholesterol and triglycerides?
• The drugs of first choice for elevated LDL
cholesterol are the HMG CoA reductase
inhibitors
• Another class of drugs for lowering LDL is the bile
acid sequestrants — colesevelam,
cholestyramine and colestipol — and nicotinic
acid (niacin).
• Other available drugs are gemfibrozil, fenofibrate
and clofibrate. These fibric acid derivatives are
primarily used for lowering high triglyceride
levels.
• The drugs of first choice for elevated LDL
cholesterol are the HMG CoA reductase
inhibitors, e.g., atorvastatin, fluvastatin,
lovastatin, pravastatin, rosuvastatin and
simvastatin. Statin drugs are very effective
for lowering LDL cholesterol levels and have
few immediate short-term side effects.
• Another class of drugs for lowering LDL is the
bile acid sequestrants — colesevelam,
cholestyramine and colestipol — and
nicotinic acid (niacin). These have been shown
to reduce the risk for coronary heart disease
in controlled clinical trials. Nicotinic acid is
preferred in patients with triglyceride levels
that exceed 250 mg/dL because bile acid
sequestrants tend to raise triglyceride levels.
• Other available drugs are gemfibrozil, fenofibrate
and clofibrate. These fibric acid derivatives are
primarily used for lowering high triglyceride
levels. Fibric acid derivatives (FADs) are a class of
drugs that have been shown to reduce the
production of very low-density lipoprotein (VLDL)
while enhancing VLDL clearance due to the
stimulation of lipoprotein lipase activity. The
drugs can reduce plasma triglyceride levels while
raising high-density lipoprotein (HDL) cholesterol
levels. Their effects on low-density lipoprotein
(LDL) cholesterol levels are less marked and more
variable
Coronary Heart Disease and Artery
Disease
Arteriosclerosis versus Atherosclerosis
Arteriosclerosis is a general term describing any
hardening (and loss of elasticity) of medium or
large arteries. It should not be confused with
"arteriolosclerosis" or "atherosclerosis".
• Arteriolosclerosis is any hardening (and loss of
elasticity) of arterioles (small arteries). It is
often due to hypertension.
• Atherosclerosis is a hardening of an artery
specifically due to an atheromatous plaque.
Atherosclerosis is the most common form of
arteriosclerosis. Atherosclerosis is
characterized by a thickening of the intima
with plaques that can contain lipid-laden
macrophages ("foam cells"). The plaques
contain free lipid (cholesterol, etc.) and are
prone to calcification and ulceration.
Other Types of Arteriosclerosis
• Arteriosclerosis obliterans is typically seen in medium
and large arteries of the lower extremity. Characterized
by fibrosis of the intima and calcification of the media.
The lumen of the vessel may be obliterated or
markedly narrowed.
• Medial calcific sclerosis (Monckeberg’s calcific
sclerosis) is seen mostly in the elderly, commonly in
arteries of the thyroid and uterus. Characterized by
calcification of the internal elastic lamina but without
thickening of the intima or narrowing of the vessel
lumen. A similar form of an intramural calcification,
presenting the picture of an early phase of
arteriosclerosis, appears to be induced by a number of
drugs that have an antiproliferative mechanism of
action.[2]
Coronary Artery Disease (CAD)
• Cocaine-induced arrhythmias and myocardial infarcts:
the heart beats faster and more forcefully, increasing
myocardial oxygen requirements
• Blood lipids and CAD
– Triglyceride: derived from ingested fat as well as
from carbohydrates and sugar
– Cholesterol: derived from ingested cholesterol and
dietary fat; saturated fat (found in meats and dairy
products) raises blood cholesterol; unsaturated fats
(found in fish, poultry, and most vegetable oils)
tends to lower cholesterol
Coronary Artery Disease
• Homocysteine and CAD: Vitamin B and folic acid are
necessary to metabolize homocysteine; elevated homocysteine
blood levels is a risk factor for atherosclerosis comparable to
high lipids, smoking and hypertension; homocysteine levels
are higher in men than in premenopausal women but increase
in menopausal women
• Chlamydia pneumoniae and CAD: Chlamydia pneumoniae has
been isolated in plaques, which may contribute to arterial
intimal damage
• Several recent studies have shown a link between dental
disease and coronary heart disease. There is a correlation of
coronary artery disease with dental plaque. Salivary levels of
Streptococcus sanguis and complaints of xerostomia. In some
cases dental disease is a larger risk factor for heart disease than
being overweight, having a high cholesterol level, not
exercising or smoking.
Coronary Heart Disease
• Caused by atherosclerosis of the large coronary
arteries, where the arteries narrow owing to
accumulation of fatty materials
• The lipid deposits, consisting of neutral fat and
cholesterol, accumulate in the arteries by diffusion
from the bloodstream
• Pathogenesis of atherosclerosis
– Endothelial injury
– Lipids accumulate and precipitate
– Secondary fibrosis and calcification
– Formation of atheroma
Coronary Heart Disease
Risk Factors
• Elevated blood lipids
• High blood pressure
• Cigarette smoking
• Diabetes
Other risk factors that play a less important role
• Obesity accompanied by high blood lipids and
elevated blood pressure
• Personality: type A personality, which is
aggressive, hard driving, and competitive
Manifestations of
Coronary Heart Disease
• Also referred to as Ischemic Heart Disease
• It is related to a decrease in blood supply to the heart
muscle caused by narrowing or obstruction of the
coronary arteries
• The clinical manifestations are quite variable
• Some individuals are free of symptoms
• Some experience chest oppression that may radiate
into neck or arms
• The pain which is caused by myocardial ischemia is
called Angina pectoris
• Stable angina: pain occurs on exertion, subsides with
rest, and is relieved by nitroglycerine
Myocardial Infarction
Location
• Most often involves left ventricle
– Anterior wall
• Left anterior descending artery distribution
– Lateral wall
• Circumflex artery distribution
– Posterior wall
• Right coronary distribution
– Massive anterior and lateral wall
• Main left coronary distribution
Myocardial Infarction
Triggers
•
Any one of four basic mechanisms may trigger a
heart attack in a patient with coronary heart
disease
1. Sudden blockage of a coronary artery, usually
caused by a clot, coronary thrombosis
2. Hemorrhage into an atheromatous plaque, usually
caused by rupture of a small blood vessel adjacent
to the plaque, which enlarges the plaque, further
narrowing the lumen of the artery
Myocardial Infarction
Triggers
3. Arterial spasm, which occurs adjacent to
atheromatous plaque and precipitates arterial
narrowing or obstruction
4. Sudden, greatly increased myocardial oxygen
requirements, caused by vigorous activity such as
running which abruptly increases cardiac output,
which in turn raises myocardial oxygen consumption
Myocardial Infarction
Complications
1. Arrhythmias: disturbances of cardiac rhythm,
most serious is ventricular fibrillation, which
leads to cessation of circulation
2. Heart failure: ventricles may be badly damaged,
unable to maintain normal cardiac function, and
heart fails
3. Intracardial thrombi: may be carried to systemic
circulation, causing infarction to brain, kidneys,
spleen
Myocardial Infarction
Complications
4. Pericarditis: infarct extends to the epicardial
surface, which leads to accumulation of fluid and
inflammatory cells in the pericardial sac
5. Cardiac rupture: a perforation may occur through
the necrotic muscle, permits blood to leak into the
pericardial sac, compressing the heart; ventricles
cannot fill in diastole, causing cardiac tamponade
6. Papillary muscle dysfunction: the papillary muscle
becomes infarcted, unable to contract normally,
causing the mitral valve to prolapse slightly into
the LA, and causing mitral insufficiency
Myocardial Infarction
Complications
7. Ventricular aneurysm: late complication, an outward
bulging of the healing infarct during ventricular
systole. Aneurysm sac fills with blood rather than
being ejected to the aorta and cardiac output is
reduced.
• Survival
– Depends on size, patient’s age, complications, other
diseases
– Mortality rates vary from 6% with small infarcts
that do not develop heart failure to more than 50%
with large infarcts that develop severe heart failure
Myocardial Infarction
Complications
Major causes of death following an MI
1. Fatal arrhythmia
2. Heart failure
3. Cardiac rupture with cardiac tamponade
• 90% of hospitalized patients survive
Myocardial Infarction
Diagnosis
• Diagnosis
– Medical history: may at times be inconclusive because
severe angina may be similar to the pain of MI
– Physical examination: will usually not be abnormal
unless patient exhibits evidence of shock, heart
failure, etc.
– Laboratory data: physician must rely on these
• Electrocardiogram: measures the transmission of
electrical impulses associated with cardiac
contraction, indicating the location and size of
infarct (elevated ST segment means MI happening
now whereas Q wave means old MI)
Myocardial Infarction
Diagnosis
• Enzyme tests: heart muscle is rich in enzymes
and proteins that regulate its activities, that
leak from the necrotic cells into circulation
when muscle becomes infarcted
• Most importantly
1. Troponin T and troponin I (proteins concerned
with muscle contractions)
2. Creatine kinase (heart muscle enzyme)
3. Lactic dehydrogenase (heart muscle enzyme)
4. Myoglobin (muscle protein)
Myocardial Infarction: Treatment
• Anticoagulant drugs: to reduce the coagulability of
blood, decreasing the likelihood of thrombus and
emboli
• Beta-blockers: reduce myocardial irritability, often
given to patients after recovering from MI
• Aspirin: small amount to inhibit platelet function,
therefore making them less likely to adhere to
roughened atheromatous plaques that can initiate a
thrombosis
Myocardial Infarction: Treatment
Factors controlled or eliminated
1. Cessation of smoking
2. Control of hypertension
3.An anticoronary diet- low cholesterol and fat
4. Weight reduction
5. Graduated exercise program
Surgical treatment: myocardial revascularization
procedures
• Bypass surgery: bypasses the obstructions in the
coronary arteries usually by means of segments of
saphenous veins obtained from the patient’s legs
Myocardial Infarction: Treatment
• Coronary angioplasty: dilates areas of narrowing
within coronary arteries, rather than bypassing
them (major surgery)
• A guided catheter introduced through skin and into
a large artery in the arm or leg threaded under
fluoroscopic control into the narrowed coronary
artery, and positioned at the site of narrowing.
Then a balloon catheter is inflated under very high
pressure, which smashes the plaque and pushes it
into the arterial wall, enlarging the lumen of the
artery