This document discusses various types of high cholesterol and triglyceride conditions. It describes familial hypercholesterolemia, which is caused by LDL receptor gene mutations and results in very high LDL cholesterol from childhood. It also discusses familial hypertriglyceridemia and conditions involving abnormalities in lipoprotein lipase or apolipoproteins that can cause high triglycerides. Finally, it mentions familial combined hyperlipidemia, which involves elevated levels of both cholesterol and triglycerides.

1. I lift up my eyes to the
mountains— where does
my help come from? My
help comes from the
Lord, the Maker of
heaven and earth.

2. Myocardial Infarct
with Rupture
CARDIAC FUNCTION TESTS –
CORONARY HEART DISEASE;
HEART FAILURE;
INFARCTION

3.  CHOLESTEROL:
1. Vital structural component of cell membranes
2. Precursor of steroid hormones and bile acids
 TRIGLYCERIDES – among the Lipids, it is the
major source of energy of cells
> Cholesterol and Triglycerides are the
most important lipids in the study and
management of CORONARY HEART
DISEASE risk.

4. Accumulated excess body fat leads to
reduced life expectancy and/or increased
health problems.
MAJOR CONCERNS

5. 1) Weigh yourself on your bathroom scale in pounds, as
well as in kilos.
2) Measure your height in inches, as well as in meters.
3) Calculate your Body Mass Index (BMI) using the two
formulas below:
1) (Standard) BMI = ___weight in lb____ x 703
(height in inches)2
2) (Metric)BMI = ___weight in kg___
(height in meters)2
or
Judge your personal BMI

6. Judge your personal BMI result against the
following scale:
•A BMI of less than 18 means you are UNDER WEIGHT.
•A BMI of less than 18.5 indicates you are THIN FOR
YOUR HEIGHT.
•A BMI between 18.6 and 24.9 indicates you are at a
HEALTHY WEIGHT.
•A BMI between 25 and 29.9 suggests you are
OVERWEIGHT for your height.
A BMI of 30 or greater indicates OBESITY.

7. KITCHENHOMECIDE

8. Water
8-12 GLASSES

10. • FOOD SOURCES RICH IN THE VARIOUS TYPES OF
FATTY ACIDS
1.SATURATED:
- Butter, cheese, meat, meat products (sausages,
hamburgers), full-fat milk and yoghurt, pies,
pastries, lard, dripping, hard margarines and
baking fats, coconut and palm oil.
2.MONOUNSATURATED
- Olives, rapeseed, nuts (pistachio, almonds,
hazelnuts, macadamia, cashew, pecan), peanuts,
avocados, and their oils.

11. 3.POLYUNSATURATED
Omega-3 polyunsaturated: Salmon, mackerel, herring,
trout (particularly rich in the long chain omega-3 fatty
acids EPA or eicosapentaenoic acid and DHA or
docosahexaenoic acid). Walnuts, rapeseed, soybean,
flax seed, and their oils (particularly rich in alpha-
linolenic acid).
Omega-6 polyunsaturated: Sunflower seeds, wheat
germ, sesame, walnuts, soybean, corn and their oils.
Certain margarines (read the label).
4. TRANS FATTY ACIDS
- Some frying and baking fats (e.g. hydrogenated
vegetable oils) used in biscuits, cakes and pastries,
dairy products, fatty meat from beef and sheep.

12. Major Lipoprotein classes
>Lower density predominantly apo-B containing particles
1. Chylomicrons (CM)
2. Very-low-density lipoprotein (VLDL)
3. Low density lipoprotein (LDL)
> apo A-containing particle
1. High-density lipoprotein (HDL)
MINOR LIPOPROTEIN CLASSES
1. IDL
2. Lipoprotein(a) or Lp (a)
3. LpX lipoprotein
4. ß-VLDL (“floating ß” lipoprotein)

13. STRUCTURE OF LIPOPROTEINS

14. Composition of Major Classes of Plasma
Lipoproteins
Protein
(%)
Cholester
ol (%)
Cholester
ol esters
(%)
Triglyceri
des (%)
Phospholi
pid (%)
Chylomicr
ons
1-2 1-3 2-4 80-95 3-6
VLDL 6-10 4-8 16-22 45-65 15-20
IDL
LDL 18-22
3)
6-8 45-50
1)
4-8 18-24
2)
HDL 45-55
1)
3-5 15-20
3)
2-7 26-32
2)

15. Major Lipoproteins
1. Chylomicrons
- very high lipid/protein ratio, thus less dense than water
and float without centrifugation; result in milky plasma
2. VLDL
- - Produced by the liver and supply the tissues with
endogenous triglycerides, primarily hepatic origin and
cholesterol; smaller and produce turbid plasma
3. LDL#
- - Constitutes 50% of the total lipoprotein mass in human
plasma
4. HDL #
- Involved in reverse cholesterol transport, the process by
which cholesterol is returned from tissue to the liver.
# Both do not scatter light or alter the clarity of plasma

16. Minor and Abnormal Lipoproteins
1. IDL
- Formed through the metabolism of VLDL in
circulation;
- Lipid content, size and density is intermediate
between VLDL and LDL; further metabolized to LDL
2. Lipoprotein (a) or Lp (a)
- Similar to LDL in terms of density and composition
- Has been speculated that Lp(a) or apo(a) might
interfere with normal thrombolysis by virtue of its
similarity to plasminogen

17. 3. LpX lipoprotein
>Abnormal protein found in :
a. obstructive biliary disease
b. In patients with familial lecithin : cholesterol
acyltransferase (LCAT) deficiency
>Composed of 90% lipids; 10% proteins
4. ß-VLDL (“floating ß” lipoprotein)
- Abnormal lipoprotein that accumulates in type 3
hyperlipoproteinemia
- Its richer in cholesterol than VLDL
- Defective catabolism of VLDL

18. PHOSPHOLIPIDS [Syn: PHOSPHOGLYCERIDES]
> Phospholipids are
similar to the
triglycerides with a
couple of exceptions.
> There are two
significant
phospholipids:
a) Lecithin
b) Sphingomyelin

19. LECITHIN–SPHINGOMYELIN RATIO
= a test of fetal amniotic fluid to assess for fetal lung immaturity.
> Lungs require surfactant, a soap-like substance, to lower the
surface pressure of the alveoli in the lungs.
Surfactant is a mixture of lipids, proteins, and glycoproteins:
lecithin and sphingomyelin being two of them.
Lecithin makes the surfactant mixture more effective.
> The outward flow of pulmonary secretions from the
fetal lungs into the amniotic fluid maintains the level
of lecithin and sphingomyelin equally until 32–33
weeks gestation, when the lecithin concentration
begins to increase significantly while sphingomyelin
remains nearly the same.

20. An L–S ratio of 2 or more indicates fetal lung
maturity and a relatively low risk of infant
respiratory distress syndrome.
 An L/S ratio of less than 1.5 is associated with a
high risk of infant respiratory distress syndrome.

21. Dyslipoproteinemia is characterized by
quantitative and qualitative
abnormalities of plasma proteins. They
include hyperlipoproteinemia and
hypolipoproteinemia.

22. FACTORS (Coronary Heart Disease)
I. Positive Risk Factors:
•Age: Male ≥45 years; Female ≥55 years or
premature menopause without estrogen
therapy.
•Family history of premature heart disease
(definite MI or sudden death before 55 years of age
in father or other female first-degree relative).
•cigarette smoking; alcoholism
*Obesity, Physical inactivity, Cigarette smoking
High carbohydrate diets

23. •Hypertension (≥140/90 mmHg or on anti-
hypertensive medication)
•Low HDL-cholesterol (<35 mg/dL)
•Diabetes mellitus; chronic renal failure, nephritic
syndrome; thyroid, & hepatic disease.
II. Negative Risk Factor
•High HDL-cholesterol (≥60 mg/dL)
> Medications as secondary causes for High Lipids:
= thiazides, estrogens, corticosteroids,
retinoids/Isotrenitoin, ciclosporin and ß-
adrenergic blockers, probucol , and certain
progestogens.

24. Phenotypes Lipoprotein elevation Major plasma lipid
elevation
1 Chylomicrons TAG
11a LDL Cholesterol
11b LDL and VLDL Cholesterol and TAG
111 β-VLDL, LDL and CM Cholesterol and TAG
1V VLDL TAG
V VLDL and CM TAG and cholesterol
Lipoprotein Phenotyping (WHO Types)
> The different hyperlipoproteinemia phenotypes
as determined by Fredrickson (table).

25. LDL Cholesterol
With LDL cholesterol the lower the better.
<100mg/dL = optimal values
100mg/dL–129mg/dL = optimal to near optimal
130mg/dL–159mg/dL = borderline high risk
160mg/dL–189mg/dL = high risk
190mg/dL and higher = very high risk
Total Serum Cholesterol
<200mg/dL = desired values
200–239mg/dL = borderline to high risk
240mg/dL and above = high risk

26. HDL Cholesterol
• With HDL cholesterol the higher the better.
40–50mg/dL for men and 50–60mg/dL for woman =
normal values
<40mg/dL for men and <50mg/dL for women =
higher risk
>60mg/dL is associated with some level of protection
against heart disease
Triglycerides
• With triglycerides the lower the better.
<150mg/dL = normal
150mg/dL–199mg/dL = borderline to high risk
200mg/dL–499mg/dL = high risk
>500mg/dL = very high risk

27. • Triglycerides, like glucose, exhibit a considerable variation
throughout the day that is related mainly to food intake.
• Triglycerides constitute an independent risk factor for
cardiovascular disease.
• The atherogenicity of hypertriglyceridemia is particularly
apparent in
a) fully developed type 2 diabetes mellitus
b) metabolic syndrome (Syndrome X)
= with its four prominent symptoms – hypertension,
hypertriglyceridemia, abdominal obesity, and insulin
resistance) called “the deadly quartet”.

28. Children
• Selectively screening (starting at 2 years of
age) children and adolescents with a family
history of premature cardiovascular disease or
those with at least one parent with high blood
cholesterol
• Intervention aimed at reducing risk is
recommended when the averaged results of
three fasting lipid profiles are
1. above the cutoffs for TC and LDL (<170 and <
110 mg/dL, respectively)
2. Elevated trigycerides (>150 mg/dL)
3. Decreased HDL-C (< 35 mg/dL)

30. Lipid and Lipoprotein Measurement
• Biologic variation
1. Women have lower values than men .
2. Age-related variation is the basis for National
Cholesterol Education Program (NCEP)
recommendation that cholesterol screening
be repeated every 5 years
3. Cholesterol esters are higher in the winter
4. Dietary intake of saturated fat, trans fat, and
cholesterol significantly influences plasma
lipid levels.

31. 5. OCP, postmenopausal estrogens and
antihypertensive drugs alter lipid levels.
6. Lifestyle and biological factors that produce
short-tem deviations from baseline lipid
values including fasting, posture, venous
occlusion, anticoagulants, recent MI, stroke,
cardiac catheterization, trauma, acute
infection and pregnancy.
-It is recommended that lipoprotein
measurements be made no sooner than 8
weeks after any form of trauma or acute
bacterial or viral infection and 3-4 months
after childbirth.

32. High Cholesterol
with
High LDL-C

33. High Cholesterol with High LDL-C
• Hyperbetalipoproteinemia (Fredrickson type 2A)
• Elevated LDL-C and normal triglycerides:
1. Polygenic (nonfamilial) hypercholesterolemia -85%
in the population may fall; develop age-related
increases in cholesterol that do not respond to
lifestyle modification
2. Familial hypercholesterolemia
3. Family defective apoB
4. Sitosterolemia

34. Familial hypercholesterolemia
= Autosomal Disorder (AD)
= Several mutations in the LDL-receptor gene on
chromosome 19
a. Heterozygous FH – associated with premature
atherosclerotic disease; 4th decade in men and women
10-15 years later. Untreated LDL-C are >220 mg/Dl
b. Homozygous FH – presents in childhood with LDL
levels >400 mg/dL; premature symptomatic CHD;
aortic stenosis, corneal arcus, tendinous xanthomata
and xanthelasma

35. Family defective apoB
- =AD
- = Disorder of apoB gene on chromosome 2 that
interferes with the recognition of apoB-100 by
the LDL receptor
- = Similar stigmata to those of FH
Sitosterolemia
- = Extremely rare autosomal recessive disorder
- = Phytosterols (plant sterols) are absorbed
- = Mutations in ABCG8 and ABCG5 genes both
located at chromosome 2p21
- = Premature CHD is present
- = Treatment: restricting dietary phytosterol intake

36. High Triglycerides
with
Normal Cholesterol

37. High Triglycerides with normal Cholesterol
• Fredrickson Types 1 and 4
• Hyperprebetalipoproteinemia (VLDL)
• Secondary causes: excess alcohol and high
carbohydrate diet
1. Diabetic dyslipidemia – atherogenic dyslipidemia (high
triglycerides, low HDL and small dense LDL) type 2
diabetes
2. Familial hypertriglyceridemia
3. Lipoprotein Lipase deficiency (hyperlipoproteinemia
type 1 or Hyperchylomicronemia)
4. ApoC-II deficiency
5. ApoC III excess

38. Familial hypertriglyceridemia
 Isolated hypertriglyceridemia (Type 4
hyperlipidemia)
- =AD
- =Fasting triglyceride levels in the 200-500
- mg/dl range
- = VLDL triglyceride production is increased in
- the setting of normal apoB production, resulting
in the formation of ‘fluffy’ triglyceride-rich VLDL
particles
- = Premature CHD

39. Lipoprotein Lipase deficiency
(hyperlipoproteinemia type 1 or
Hyperchylomicronemia)
- =Autosomal recessive; childhood
- =Abdominal pain and pancreatitis
- =Defective or absent LPL
- =Do not develop premature CHD-chylomicrons
themselves are not atherogenic
- =Fasting >100 mg/dL and rise 10,000 mg/dL
postprandially
- Treatment:
1. Low fat diet
2. Fat soluble vitamins supplementation
3. Drug therapy to lower endogenous VLDL production

40. ApoC-II deficiency
- =Absence of apoC-II creates functional LPL
deficiency
- =Autosomal recessive
- = Children and young adults
- = Recurrent bouts of abdominal pain and
pancreatitis
- = Several defects in apoC-II gene
- = Treated with plasma transfusions during
severe hypertriglyceridemia

41. ApoC-III excess
- =apoC-III interferes with the activity of
lipoprotein lipase and binding of the carboxy-
terminal to the apolipoprotein B, preventing the
binding of lipoproteins to the LDL receptor
- Increased in:
1. Diabetics
2. Diabetics with hypertriglyceridemia

42. High Cholesterol
with
High Triglycerides

43. High Cholesterol with High Triglycerides
=Fredrickson types 2B and 3
1. Familial combined hyperlipidemia (type 2B)
2. Dysbetalipoproteinemia
3. Hepatic lipase deficiency

44. Familial combined hyperlipidemia (type
2B)
- =The most common hyperlipoproteinemia
- =Variety of lipoprotein phenotypes (LDL,
- VLDL)
- =Genetic basis is unknown

45. Dysbetalipoproteinemia (type 3)
=Abnormal LDL (IDL) that appears as a broad beta
electrophoretic band
= Apo E is present on chylomicrons, VLDL, IDL and
chylomicron remnants
= 3 electrophoretic isoforms of apoE:
1. E-3 – is the most common
2. E-4
3. E-2 – low affinity for LDL receptor
- =A pathognomonic feature: a broad band between
VLDL and LDL known as ‘abnormally migrating
beta lipoprotein’ or ß VLDL
= Useful screen: VLDL-C/Triglyceride ratio is > 0.3
= Normally, the VLDL-C/Triglyceride ratio is 0.2
= Premature atherosclerosis is prevalent: femoral and
abdominal arteries

46. Hepatic lipase deficiency
- =Mutations of HL gene
- = Rare familial disorder associated with combined
hyperlipidemia
- = Characterized by TC levels of 250-150 mg/dL and
= TG of 400-8000 mg/dL
- = The TC/TG ratio is not increased

47. Isolated
Low total cholesterol

48. Isolated Low total cholesterol
= Associated with defective apoB snthesis or
metabolism, leading to low or nonexistent levels of
apo-B lipoproteins such as CM, VLDL and LDL
1. Abetalipoproteinemia
2. Hypobetalipoproteinemia
3. Chylomicron retention disease

49. Abetalipoproteinemia
= Autosomal recessive
= Premature degradation of apoB due to defects in the
hepatic microsomal transport protein, which is
essential for apoB secretion.
=Neither apoB-48 or apoB-100 is present in the plasma
=Childhood or adolescence with fat malabsorption,
hypolipidemia, retinitis pigmentosa, cerebellar
ataxia, and acanthocytosis
=Fat soluble vitamin deficiencies (A,E,K) due to
malabsorption. Vitamin D does not require
chylomicrons for absorption and therefore is not
typically deficient
= Replacing vitamin E stores improves retinal and
peripheral neuropathic symptoms

50. Hypobetalipoproteinemia
= Autosomal dominant disorder
= Nonsense or missense mutations in the apoB
gene leading to very low LDL-C levels
=Homozygous individuals:
1. TC levels < 50 mg/dL
2. Fat malabsorption and low plasma cholesterol
levels at young age
3. Progressive neurologic degenerative disease
4. Retinitis pigmentosa
5. Acanthocytosis
-
=Treatment with high dose vitamin E(100-300
mg/kg/day)

51. Chylomicron retention disease
=Presents in childhood
=Fat malabsorption and low circulating lipids
=Only B-48 is affected
=Disorder associated with SARA2 gene on
chromosome 5q3

52. Isolated
Low HDL-C

53. Isolated low HDL-C
=Are associated with CHD, because insufficient
HDL is available to participate in reverse
cholesterol transport, the process by which
cholesterol is eliminated from peripheral tissue
1. Familial hypoalphalipoproteinemia
2. ApoA-1 deficiency and ApoC-III deficiency
3. ApoA-I variants
4. Tangier disease
5. Lecithin:Cholesterol Acyltransferase (LCAT)
deficiency

54. Familial hypoalphalipoproteinemia
- =AD
- =Men have HDL-C levels <30 mg/dL and women
have HDL-C levels <40 mg/dL
- = Hepatic lipase or apoA-I/C-III/A-IV gene
defects
- = Mutations in the ABCA1 gene
- = Premature CHD is present

55. ApoA-1 deficiency and ApoC-III deficiency
- = Autosomal recessive
- = Mutations in the ApoA-I gene and deletions
- gene rearrangements at the apoA-I/C-III/A-IV
gene locus on the long arm of chromosome 11
- = HDL-C levels are < 5mg/dL
- = Corneal opacification and premature
Coronary disease

56. ApoA-I variants
= Amino acid substitution in the ApoA-I gene
= Increase catabolism of HDL and ApoA-I
= Autosomal recessive inheritance
= Low levels of HDL-C (10 mg/dL)
= Corneal opacifications, xanthomata, and premature
coronary disease
ApoA-I Milano
= AD
= Low HDL-C levels but not associated with premature
coronary disease

57. Tangier disease
= Autosomal recessive
= Low cholesterol and high triglycerides
= Homozygous: hepatosplenomegaly, peripheral
neuropathy, orange tonsils and premature
coronary disease
= Mutations in the ABCA1 gene
= ABCA1 protein enables cholesterol to exit the cell
where it combines with ApoA-I to form the HDL. In
the absence of ABCA1 activity, cholesterol
accumulates in cells

58. Lecithin:Cholesterol Acyltransferase
(LCAT) deficiency
= Autosomal recessive
= Mutations in the LCAT gene
= Without LCAT, most cholesterol remains unesterified
and HDL synthesis is impeded
- 2 forms:
1) Classic (complete) familial LCAT deficiency
 = HDL-C levels are <10 mg/dL
 = Total cholesterol are normal to high
2) Partial deficiency (Fish-eye disease)
 Premature CHD

59. Isolated
High HDL-C

60. Isolated High HDL-C
= Cholesteryl Ester Transfer Protein Gene Defects
= CETP facilitates the transfer of cholesteryl esters from
HDL to apoB-100 rich proteins (VLDL and LDL) in
exchange of triglycerides
= Autosomal recessive
= Transfer of cholesteryl esters is inhibited
= HDL particles are large and laden with cholesteryl
ester
- apoA-I is increased, HDL –C >100 mg/dL
= Associated increased risk of CHD

61. MEASUREMENT OF BLOOD LIPIDS
When measuring blood lipids several important
guidelines for blood sampling and storage must be
remembered.
1) Fasting.
- ideal fasting: 12 –14 hours
 When the patient cannot
tolerate such schedule, 9 hours
fasting may be acceptable.
 Chylomicrons are completely
cleared within 6-9 hours and
their presence after 12 hrs is
considered abnormal.

62. - Total cholesterol and HDL-C can be measured
in nonfasting individuals.
- Fasting has little effect on plasma TC levels
and although nonfasting HDL-C levels can be a
few mg/dl lower than fasting levels, this
should not lead to misclassification of
patients with low HDL levels.
- When triglycerides and LDL-C are being
measured, fasting becomes a requirement.

63. (standard position)
2) Patient’s position
Change in position, like when a standing patient
reclines, extravascular water transfers to the vascular
system and dilutes nondiffusible plasma
constituents.
This results in a decrease of 10 % in the
concentration of total
cholesterol, LDL-chol,
HDL-chol, apo A-1 and
Apo B; 50% decrease
has been reported with
triglyceride levels.

64. 3) Application of tourniquet.
Prolonged tourniquet application will increase
the lipid concentration due to venous stasis.
-Prolonged venous occlusion can lead to
hemoconcentration and cholesterol increases of
10-15%.
-> Tourniquet
should not be
applied for more
than a minute or
2.

65. >Venous vs. capillary samples
- Measurements in capillary blood samples
seem to be a little lower than in venous
samples.
4) Sample.

66. 5) Anticoagulant.
> EDTA is the preferred anticoagulant.
Citrate exerts large osmotic effects resulting
in artifactually low plasma lipid and
lipoprotein concentration.

67. ESTIMATION OF LIPOPROTEINS
Measurement of lipoproteins are used to
diagnose errors in lipoprotein metabolism and
confirm levels of cholesterol to adequately assess
possible risk for coronary disease.

68. LIPID PROFILE
(Combined Methods / Panel)
Typically, the lipid profile includes measurements
of triglycerides, total cholesterol, HDL-cholesterol,
LDL-cholesterol, and VLDL -cholesterol.

69. Friedewald Equations:
plasma TAG
VLDL-cholesterol = ------------------------
(in mg/dL) 5
plasma TAG
VLDL-cholesterol = -------------------------
(in mmol/L) 2.175
LDL-cholesterol = total cholesterol –
HDL-cholesterol - VLDL-cholesterol

70. Delong Equations:
Plasma TAG
VLDL-cholesterol = ------------------------
(in mg/dL) 6.5
Plasma TAG
VLDL-cholesterol = ------------------------
(in mmol/L) 2.825
LDL-cholesterol = total cholesterol -
HDL-cholesterol - VLDL-cholesterol

71. STANDING PLASMA TEST
The standing plasma test is used to determine the
presence of fasting chylomicrons in the blood.
This is done by placing 2ml plasma in a test tube
and leaving it in the refrigerator.
Examine the plasma the following day.
Chylomicrons float to the top giving a creamy
layer.

72. VLDL remains in the infranatant imparting
opalescence or turbidity to the plasma.
LDL and HDL are too small to scatter light
therefore, there is no apparent effect on plasma.

73. Xanthoma
Xanthelasma

74. BNP or NT-proBNP
Either BNP or NT-proBNP (prohormone) may be
used to help detect, diagnose, and evaluate the
severity of HEART FAILURE.
Testing may be performed if a person has
symptoms such as swelling in the legs (edema),
difficulty breathing, shortness of breath, and
fatigue.
It can be used, along with other cardiac
biomarker tests, to detect heart stress and damage
and/or along with lung function tests to distinguish
between causes of shortness of breath.

75. >Heart failure can be confused with other
conditions, and it may co-exist with them. BNP and
NT-proBNP levels can help differentiate between
heart failure and other problems, such as lung
disease.
Higher-than-normal results suggest that a person
has some degree of heart failure, and the level of
BNP or NT-proBNP in the blood is related to its
severity.
Higher levels of BNP or NT-proBNP are often
associated with a worse outlook (prognosis) for the
person.

76. > Both are also typically increased in patients
with left ventricular dysfunction, with or without
symptoms (BNP accurately reflects current
ventricular status, as its half-life is 20 minutes,
as opposed to 1–2 hours for NT-proBNP).
>Normal results indicate that the person's
symptoms are likely due to something other
than heart failure.
> BNP can also be elevated in renal failure as
it is reliant solely on the kidney for excretion.
> For patients with heart failure, BNP values will,
in general, be above 100 pg/ml.

77. 3/12/2023
ACUTE MYOCARDIAL INFARCTION

78. 3/12/2023

79. 3/12/2023

80. 3/12/2023

81. . Plasma Enzyme Activities After Myocardial Infarct
•CK (CK-MB fraction or CK2). This is the first
enzyme to rise making it a sensitive index for
acute MI.
•AST. Levels as high as 4-10 times the upper
normal limit may be seen during acute MI. This is
increased within 12 hours. It reaches its peak on
the second day and returns to normal on the 5th
day. It is considered a diagnostically redundant
cardiac enzyme.
*LD (LD1 fraction). This is the last enzyme to rise.
It appears within 24 hours. It has, however, a
longer persistence (prolonged up to 10-14 days).

82. •CREATINE KINASE
•The levels of CK in the blood is a specific index of
injury to myocardium and skeletal muscles.
•It is also increased in pulmonary infarcts and
edema.
•CK Isoenzymes
CK isoenzymes are dimmers made up of either the
B subunit or the M subunit or both. There are three
CK isoenzymes in the body.

83. •They are:
CK-BB or CK1: It is the brain type and is found
in greater concentrations in the brain, bladder,
lungs, and thyroid. It migrates the fastest toward
the anode during electrophoresis. It is
characteristically increased in brain injury.
CK-MB or CK2: It is the heart or the hybrid type.
It is found more in the heart and skeletal muscles.
It is increased in acute myocardial infarct (MI) and
sub-arachnoid injury.
CK-MM or CK3: It is the skeletal muscle type. It
is found in the heart or skeletal muscles. It
migrates the slowest during electrophoresis. It is
increased in muscle trauma and major surgery.

84. •Normal values differ between genders because of
the differences in muscle mass.
Males: 25-90 IU/mL (0.42-1.51 mmol/L)
Females: 10-70 IU/mL (0.17-1.18 mmol/L)

85. • LACTATE DEHYDROGENASE
• Lactate dehydrogenase (LD) is found in all tissues but it
very rich in the myocardium, kidney, liver, muscles and red
blood cells.
• Normal value is 80-280 U/L at 37 ⁰C.
•LD Isoenzymes
The isoenzymes of LD are tetramers. These
tetramers are built from two types of subunits
namely the H (heart) subunit which has a higher
affinity for lactate and M (muscle) subunit which has
a higher affinity for pyruvate.

86. •The LD isoenzymes are:
•LD1 (HHHH) and LD2 (HHHM): These are seen in the
heart, red blood cells, and renal cortex. They have
the greatest anodic mobility during electrophoresis.
They are also heat stable.
•LD3 (HHMM): This isoenzyme is seen in the lungs,
lymphocytes, spleen, pancreas, and brain.
•LD4 (MMMH) and LD5 (MMMM): These are seen in
the liver and the skeletal muscles. They have the
least anodic mobility and they are present in high
concentrations in the liver.

87. A B
An LD 1:2 “flip” was apparent.
Electrophoresis

88. LD isoenzyme scan
•Viral hepatitis

89. Electrophoresis
> = means Higher peak

90. 3/12/2023
•A glycolytic enzyme which may
have clinical value for AMI:
> Aldolase (ALS): It is a marker of
muscle disease. ALS-A
isoenzyme is largely in the
skeletal muscle.

91. 3/12/2023
TROPONINS
• Cardiac muscle
= similar to skeletal muscle but
branched and interconnected
= lack the end plates and have
involuntary control.
• = contractile proteins compose of
overlapping thick and thin filaments which
slide past each other to produce muscle
contraction

92. 3/12/2023
• thick filament = composed of myosin which
contains adenosine triphosphatase (ATPase)
activity and forms cross-bridges with actin.
• thin filament = consists of actin, tropomyosin
and troponin regulatory complex:
a) troponin C (TnC) that binds Ca2+ to initiate
muscle contraction,
b) troponin I (TnI) that inhibits actin-myosin
coupling through the inhibition of ATPase
activity
c) troponinT (TnT) binds to tropomyosin and
stabilizes the complex on the actin filament

93. 3/12/2023

94. 3/12/2023
Cardiac troponin monitoring for detection of
myocardial injury
= designated the new standard for differentiating
the diagnosis of unstable angina and non-ST
elevation myocardial infarction (NSTEMI) in acute
coronary syndrome (ACS) patients.

95. 3/12/2023
• DIAGNOSTIC VALUE OF CARDIAC TROPONINS
Cardiac troponin monitoring for detection of
myocardial injury
= designated the new standard for
differentiating the diagnosis of unstable
angina and non-ST elevation myocardial
infarction (NSTEMI) in acute coronary
syndrome (ACS) patients.

96. 3/12/2023
• Acute myocardial infarction
• Creatine kinase (CK)-MB = gold standard marker
of myocardial necrosis used in the evaluation of
acute coronary syndromes (Roberts and Sobel,
1973).
• = predominantly located in myocardial cells
• = 1–3% of the total CK found in skeletal muscle,
and is also present in smaller quantities in other
tissues, such as intestine, diaphragm, uterus,
and prostate which limits its utility in clinical
practice.

97. Recently, cardiac troponins have
replaced the creatine kinase (CK)-MB
for both diagnosis and risk
stratification in myocardial necrosis.
The early release kinetics of cTnI and
cTnT following cardiac cell necrosis,
elevation starts within 2-3 hours,
allows detection at 3–6 h after
symptom onset during MI, peaks in
approx. 24 hours and may remain
elevated for 7–14 days.

98. 3/12/2023
• Troponins have overtaken the traditional
‘cardiac enzymes’, and can provide valuable
information of the likelihood of a myocardial
infarct (MI).
• Although troponins are recognized as having
diagnostic advantages over older cardiac
enzymes, it is important the test is requested
appropriately.
• This is mainly because results are typically not
useful in the first one to three hours and
maximum sensitivity is not until after 10 or
more hours following onset of acute MI.

99. 3/12/2023
• Elevations of cTnI and cTnT
= must be measured serially over time to
adequately exclude MI.
=Blood should be obtained for testing on hospital
admission, at 6–9 h and again at 12–24 h if the
earlier samples are negative and the clinical
index of suspicion is high.
> Troponin T has a short half-life of about 90 min,
and persistent elevation on day 3 or 4 reflects
degradation of the contractile elements which is
a hallmark of irreversible cell injury

100. 3/12/2023
• Common causes of false positive troponin
include: heterophilic antibodies, rheumatoid
factor, fibrin clots, micro-particles and
analyzer malfunction.

101. •AMINOTRASFERASES
•Aspartate aminotransferase (AST) catalyzes the following
reversible reaction. (Serum glutamic oxaloacetic transaminase)
AST
Aspartate + α-ketoglutarate ↔ Oxaloacetate + Glutamate
AST (SGOT) is rich in the cardiac muscle, liver
mitochondria, skeletal muscle, kidney, and pancreas.
•Alanine aminotransferase (ALT) catalyzes the following
reversible reaction. (Serum glutamic pyruvic transaminase)
ALT
Alanine + α-ketoglutarante ↔ Pyruvate + Glutamate
ALT (SGPT) is rich in the liver cytosol, kidney, heart,
skeletal muscle, and pancreas.

102. AST/ALT Ratio (De Ritis Ratio)
> When greater than 2.0, it is more likely to be
associated with viral hepatitis, alcoholic
hepatitis[4] or hepatocellular carcinoma
> When greater than 1.0 but less than 2.0, it is likely
to be associated with cirrhosis
> It is normally less than 1.0
> However, the AST/ALT ratio is less useful in
scenarios where the liver enzymes are not
elevated, or where multiple conditions co-exist.

103. The AST/ALT or De Ritis ratio can be very high in
alcoholic or toxic liver disease (3-4:1).
•> It is low in acute or chronic viral hepatitis
where ALT is high (reversed De Ritis ratio).
•> If the ratio is <1, it could indicate acute
hepatocellular injury (due to high ALT).
A high ALT indicates mild hepatocellular
damage while a high AST indicates severe
hepatocellular damage (high AST/ALT ratio).

104. Increased levels prompts diagnosis of acute
hepatitis.
ALT is not associated with MI. It is increased in
heart failure with attendant hepatic necrosis.
Applications of ALT Levels. ALT is more
specific in detecting liver diseases in non-
alcoholic asymptomatic patients.
Transaminases levels are often compared with
results of other tests, such as alkaline phosphatase
(ALP), total protein, and bilirubin to help
determine which form of liver disease is present.

105. > Levels as high as 4-10 times the upper
normal limit may be seen during acute
MI.
Applications of AST Levels. AST may be used
to monitor therapy of potentially hepatotoxic
drugs.
It is used for diagnosis of chronic hepatitis.
 It is also increased in cardiovascular disease.

106.  Pyridoxal phosphate or vitamin B6 is needed as
a cofactor of the transaminases. This molecule
acts as a carrier of the amino group from one acid
to another.
 Serum or plasma may be used because the
enzymes are not inhibited by common
anticoagulants.
 The enzyme is stable at room temp for 48 hrs
and for 1 week at 4 ⁰C.
 The normal values are:
AST: 5-30 U/L at 37 ⁰C
ALT: 6-37 U/L at 37 ⁰C

107. 3/12/2023

108. ENZYME TIME OF
RISE
(hours)
Peak
Activity
(hours)
Return to Normal
(days)
CK(CPK) 2-4 12-36 2-4
AST (SGOT) 4-12 24-48 3-4
Aldolase (ALD) 6-8 24-48 3-4
LD (LDH) 10-24 48-96 7-10
Troponin I 3-12 10-24 3-10
Troponin T 3-12 12-48 5-14
Myoglobin 2-4 6-12 24-36 hours
Table 1. Cardiac Marker Changes Over Time