ischaemic heart disease ila final 14 april 2011
TRANSCRIPT
A 53-year-old man presents with recurrent chest pain that has gotten progressively worse over the last several weeks.
He says that approximately a year ago the pain would occasionally occur when he was mowing his yard but now the pain sometimes occurs while he is sitting in a chair at night reading a book.
The pain which is localized over the sternum lasts much longer now than it did a few months ago.
What type of disease does this individual have at present?
Myocardial IschaemiaAn imbalance between the supply of oxygen
and the myocardial demand resulting in myocardial ischaemia.
Most occurs because of atherosclerotic plaque within one or more coronary arteries.
Limits normal rise in coronary blood flow in response to increase in myocardial oxygen demand
Oxygen Carrying CapacityThe oxygen carrying capacity relates to the
content of hemoglobin and systemic oxygenation
When atherosclerotic disease is present, the artery lumen is narrowed and vasodilatation is impaired
Coronary blood flow cannot increase in the face of increased demands and ischemia may result
This causes myocardial cells to switch from aerobic to anaerobic metabolism, with a progressive impairment of metabolic, mechanical, and electrical functions.
Angina pectoris is the most common clinical manifestation of myocardial ischemia. It is caused by chemical and mechanical stimulation of sensory afferent nerve endings in the coronary vessels and myocardium.
During ischemia, ATP is degraded to adenosine, which, thay diffuses to the extracellular space, causing arteriolar dilation and anginal pain.
Adenosine as a pain messenger: Adenosine induces angina mainly by stimulating the A1 receptors in cardiac afferent nerve endings.
The coronary blood flow may be reduced by a mechanical obstruction due to- atheroma- thrombosis- spasm- embolus- coronary ostial stenosis- coronary arteritis
There can be reduction in the flow of oxygenated blood due to :-
- Anaemia- Carboxyhaemoglobinaemia- HypotensionIncreased demand for oxygen occurs in:-- increase cardiac output (e.g. thyrotoxicosis)- myocardial hypertrophy (e.g.hypertension or aortic stenosis)
AnginaWhen ischemia results it is frequently
accompanied by chest discomfort: Angina Pectoris
Angina is a symptom not a diseasechest discomfort associated with abnormal myocardial function in the absence of myocardial necrosis
May develop sudden increase in frequency and duration of ischemic episodes occurring at lower workloads than previously or even at rest
In the majority of patients with angina, development of myocardial ischemia results from a combination of fixed and vasospastic stenosis
WHO Diagnosis of Acute Myocardial Infarction (AMI):
Presence of two of the three criteria:1. History of characteristic chest pain2. Electrocardiographic changes (pathologic Q waves, ST segment and T wave changes)3. Typical pattern of serum cardiac enzyme
rise, peak and return to reference range
Risk factors
Risk factorsFamily HistorySmokingHypertensionDiabetes MellitusHypercholesterolaemiaLack of exercise
What are the investigations you advice for him?
a. ECG b. serum cardiac enzymes
c. Lipid profiled. chest x-ray e. coronary angiogram
Ischaemic heart disease
Laboratory Investigations- Specimen Collection:
Serum is the specimen of choice
Heparinized plasma is acceptable
Venous whole blood for rapid Cardiac Troponin T.
- Collection Time: Serial specimens collected at appropriate
time intervals
Serial measurements are most useful
Samples are drawn on admission
at 2-4 hours
at 6-8 hours
at 12 hours
Lipid Disease PatternsHigh cholesterol with High LDL-CHigh Triglycerides with Normal CholesterolHigh Cholesterol and High Triglycerides with
or without Low HDL-CLow Total Cholesterol with Low or Normal
HDLIsolated Low HDLIsolated High LDLLp (a) Lipoprotein Excess
200-500 mg/dl >500 mg/dl< 200 mg/dl
Diet andretest inone year
Evaluate for risk factors:
AlcoholismDiabetes MellitusGlycogen Storage
DiseaseHypertensionHyperuricemiaHypothyroidism
MedicationsOral contraceptives
PancreatitisPregnancy
Renal disorder
No riskfactors+ Risk factor or+ Family history
Diet anddrugsDiet
Male > 160 mg/dl Female > 135 mg/dl
Lipid Interpretation for Coronary Heart Disease
Lipids normalT Chol <200 mg/dlLDL <130 mg/dlHDL >45 mg/dl
Lipids normalT Chol <200 mg/dlLDL <130 mg/dlHDL >45 mg/dl
Repeat after 5 yrsRepeat after 5 yrs
Lipids abnormalT Chol 200-239 mg/dlLDL 130-159 mg/dlHDL 35-45 mg/dl
Lipids abnormalT Chol 200-239 mg/dlLDL 130-159 mg/dlHDL 35-45 mg/dl
Lipids abnormalT Chol >240 mg/dlLDL >160 mg/dlHDL <35 mg/dl
Lipids abnormalT Chol >240 mg/dlLDL >160 mg/dlHDL <35 mg/dl
RISK FACTORSCerebrovascular diseaseCigarettes >10/dayDiabetes mellitusFH of CHD/vascular diseaseHypertensionMaleOcclusive peripheral vascular diseaseOverweight >30%
RISK FACTORSCerebrovascular diseaseCigarettes >10/dayDiabetes mellitusFH of CHD/vascular diseaseHypertensionMaleOcclusive peripheral vascular diseaseOverweight >30%
Diet and/orDrugs
Diet and/orDrugs
DietRetest in 1 yr
0-1 risk factorNo coronary HD0-1 risk factorNo coronary HD
2 or morerisk factors2 or morerisk factors
Plasma cardiac markers of post- myocardial infarction.
CK = creatine kinase AST = aspartate transaminase LDH = lactate dehydrogenaseMYOGLOBINTRPONIN
MYOGLOBIN low-molecular-weight heam-containing
protein found in both skeletal and cardiac muscle.
Typical rise occurs within 2-4 hours after the onset of acute myocardial infarction. This is useful for the early diagnosis of acute myocardial infarction, as this rise is generally earlier than used cardiac markers.
myoglobin is not cardiac specific, better used in conjunction with other markers.
Creatine kinase and CK-MB Creatine kinase acts as a regulator of high-energy
phosphate production and utilization within contractile tissues.
Cytoplasmic CK is a dimer, composed of M and/or B subunits, which associate forming CK-MM, CK-MB and CK-BB isoenzymes
Cytosolic CK regenerate ATP from ADP, using PCr. There are two mitochondrial creatine kinase
isoenzymes, Mitochondrial creatine kinase is directly involved
in formation of phospho-creatine (PCr) from mitochondrial ATP,
CKCK-MM is the main isoenzyme found in
striated muscleCK-MB is found mainly in cardiac muscle
Trace amounts of CK-MB are found in skeletal muscle.
CK-BB is the predominant isoenzyme found in brain, colon, ileum, stomach and urinary bladder.
CKMost of the CK released after a myocardial
infarction is, in fact, the MM isoenzyme CK-MM.
A raised plasma total CK activity, due to entirely CK-MM, may follow recent intramuscular injection, exercise or surgery (NON SPECIFIC)
limited prognostic value
CK CK-MB also exists as two isoforms, namely
CK-MB1 and CK-MB2. CK-MB2 is predominantly released from
the myocardium. CK-MB that is routinely assayed reflects the
sum of the two isoforms. Normally CK-MB1 predominates in plasma,
but after an acute myocardial infarction this is reversed.
CK- MM has longer half life than MB.
CK Plasma enzyme activity is raised in about 95
% of cases of myocardial infarction and are sometimes very high.
second rise of plasma enzyme → extension of the damage
A prolonged rise in plasma CK →may suggest a cardiac ventricular aneurysm .
plasma enzyme activity does not usually rise significantly after episode of angina pectoris without infarction.
An increase in CK-MB in the plasma may not be seen until 4-8 h after the onset of chest pain.
When the diagnosis is not obvious, an elevated CK-MB or an increase in CK-MB of more than 15% over a 4-h period, even if both values are within the reference range, are suggestive of myocardial infarction.
The detection of a trend by serial measurements, may provide more information than single measurements.
ASTHepatic congestion due to right-sided heart
dys function may contribute to the rise of plasma AST activity
If there is primary hepatic dysfunction, plasma AST rises whereas LDH1 activity usually remains normal.
The sequence of changes in plasma AST activity in MI are similar to those of CK .
AST and LDHAST and LDH measurements are rarely of
practical value in the management of patients with suspected myocardial infarction.
Exceptionally, when a patient with chest pain presents late, measurement of LDH may be helpful as this enzyme remains elevated in the plasma for several days following myocardial infarction.
CARDIAC TROPONIN Cardiac troponins have been recommended as
the biochemical cardiac marker of choice. Troponins are muscle-regulator/ proteins
present in skeletal and cardiac muscle. Three troponins (TnC), (Tnl) and (TnT). Tn I and TnT appear in the plasma 48 hours
after symptoms of acuteMI, and are best measured 12 hours after the start of chest pain useful in the late presentation of chest pain.
An increased Tnl or TnT concentration is a sensitive marker of occult myocardial damage.
CARDIAC TROPONINAn increased Tnl or TnT concentration is a
sensitive marker of occult myocardial damage even in non-ischaemic conditions.
Troponin T may be elevated in patients with chronic renal failure and thus may not be so cardiac-specific
They are therefore not early markers of acute myocardial infarction, but they do stay elevated for about 7-10 days in plasma, which makes them useful in the late presentation of chest pain
CARDIAC TROPONIN
The 3 components of Troponin complex :
1. Troponin C = Ca++ binding.2. Troponin I = Actinomyosin ATPase inhibiting
element. * It binds actin inhibiting its binding to myosin * It is encoded by 3 different genes, giving rise to 3 isoforms. - Slow Skeletal Muscle - Fast - Cardiac Cardiac Muscle
* It is released within 4 hrs of the onset of ischemic Symptoms of myocardial infarction. So, it is used as a marker of myocardial infarction. peaks 14-24hrs and remains elevated for 3-5
days.
3. Troponin T = Tropomyosin binding element Its level increases within 6 hours of myocardial
infarction. Peaks at 72 hrs remains elevated 7-10 days.
2 Isoforms in the heart TnT1+ TnT2 are used as cardiac markers.
Troponin complex consist of 3 components
actintroponin
tropomyosinmyosin binding site
Ca2+Ca2+
Ca2+
Ca2+
the calcium ions bind to the troponin and changes its shape
Ca2+Ca2+
Ca2+
Ca2+
the troponin displaces the tropomyosin and exposes the myosin binding sites
Ca2+Ca2+
Ca2+
Ca2+
the bulbous heads of the myosin attach to the binding sites on the actin filaments
Ca2+ Ca2+
Ca2+
the myosin heads change position to achieve a lower energy state and slide the actin filaments past the stationary myosin
Ca2+ Ca2+
Ca2+APi PiPi
APi PiPi
APi PiPi
ATP binds to the bulbous heads and causes it to become detached
Ca2+ Ca2+
Ca2+
APi Pi
Pi
APi Pi
Pi
APi Pi
Pi
hydrolysis of ATP provides the energy to “re-cock” the heads
Ca2+ Ca2+Ca2+
APi Pi
Pi
APi Pi
Pi
APi Pi
Pi
calcium ions are re-absorbed back into the T system
APi Pi
Pi
APi Pi
Pi
APi Pi
Pi
the troponin reverts to its normal shape and the tropomyosin move back to block the myosin binding sites
Ischaemia-modified albuminA new marker, ischaemia-modified albumin,
is raised in the presence of myocardial ischaemia and may be used in the future in conjunction with conventional cardiac markers.
Increased coronary artery disease risk is least correlated with the following EXCEPT:a. elevated total cholesterol levels b. elevated LDL levels c. elevated HDL levels d. elevated Lipoprotein (a) levels e. elevated triglyceride levels
Increased coronary artery disease risk is least correlated with the following EXCEPT:a. elevated total cholesterol levels b. elevated LDL levels c. elevated HDL levels d. elevated Lipoprotein (a) levels e. elevated triglyceride levels
Which cardiac enzyme would you expect to rise within the next 3 to 8 hours :
a.Creatine kinase (CK)b.Lactic dehydrogenase (LDH)c.LDH - 1d.LDH – 2
Which cardiac enzyme would you expect to rise within the next 3 to 8 hours :
a.Creatine kinase (CK)b.Lactic dehydrogenase (LDH)c.LDH - 1d.LDH – 2
The laboratory tests that would confirm a diagnosis of myocardial infarction include:
a.LDH, CK-MB and ASTb.Serum calcium, and APPTc.Sedimentation rate, and ALTd.Paul-Bunnell and serum potassium
The laboratory tests that would confirm a diagnosis of myocardial infarction include:
a.LDH, CK-MB and ASTb.Serum calcium, and APPTc.Sedimentation rate, and ALTd.Paul-Bunnell and serum potassium
Elevation of which of the following serum enzyme markers would be most useful in diagnosing a myocardial infarction in a patient who comes to your office 3 days after an episode of severe and prolonged substernal chest pain?
a. LDH isoenzymes b. CK.MB c. TroponinI d. myoglobin
Elevation of which of the following serum enzyme markers would be most useful in diagnosing a myocardial infarction in a patient who comes to your office 3 days after an episode of severe and prolonged substernal chest pain?
a. LDH isoenzymes b. CK.MB c. TroponinI d. myoglobin
When cardiovascular disease is a concern, reduction of the saturated fat in the diet and substitutes made of polyunsaturted fat is desired. When teaching the client about this diet the one should instruct the patient to avoid :
a.Fishb.Corn oil c.Whole milkd.Soft margarine
When cardiovascular disease is a concern, reduction of the saturated fat in the diet and substitutes made of polyunsaturted fat is desired. When teaching the client about this diet the one should instruct the patient to avoid :
a.Fishb.Corn oil c.Whole milkd.Soft margarine
Which protein inhibits the interaction of actin and myosin?
a. troponin C b. troponin T c. troponin I d. tropomysin
Which protein inhibits the interaction of actin and myosin?
a. troponin C b. troponin T c. troponin I d. tropomyosin
myocardial infarctionMany patients with myocardial infarction
have a typical history of crushing central chest pain, perhaps radiating to the arm or jaw, associated with typical ECG changes. myocardial infarction can, however, present atypically, or even be clinically silent, particularly in the elderly
Troponin I and TnT appear in the plasma 4-8 hours after symptoms of acute myocardial infarction, and are best measured 12 hours after the start of chest pain.
They are therefore not early markers of acute myocardial infarction, but they do stay elevated for about 7-10 days in plasma, which makes them useful in the late presentation of chest pain