postmortem chemistry
DESCRIPTION
Postmortem biochemistry is usually performed by the hospital autopsy pathologist, but it can be useful in a forensic setting. The pathologist should be aware of the value and limitations of postmortem biochemistry because he will inevitably encounter a number of cases that require investigation into the decedent’s metabolic state.TRANSCRIPT
Postmortem Chemistry(Medicolegal Significance)
Postmortem Chemistry(Medicolegal Significance)
Mamdouh K. ZakiMamdouh K. ZakiDoctorate and MSc of Forensic Medicine
Jeddah Forensic Medicine Administration,
Ministry of Health - Kingdom of Saudi Arabia
Doctorate and MSc of Forensic Medicine
Jeddah Forensic Medicine Administration,
Ministry of Health - Kingdom of Saudi Arabia
Correspondence:
email: mklz@hotmail or
Mobile: 00966501411243
Correspondence:
email: mklz@hotmail or
Mobile: 00966501411243
بسم الله الرحمن الرحيم
إن الله يأمركم أن تؤدوا األمانات
إلى أهلها
وإذا حكمتم بين الناس أن
تحكموا بالعدل
صدق الله العظيم58ســـورة الـنسـاء – اآلية
بسم الله الرحمن الرحيم
إن الله يأمركم أن تؤدوا األمانات
إلى أهلها
وإذا حكمتم بين الناس أن
تحكموا بالعدل
صدق الله العظيم58ســـورة الـنسـاء – اآلية
“Indeed, Allah commands you to render trusts to whom they are due and when you judge between people to judge with justice. Excellent is that which Allah instructs you. Indeed, Allah is ever Hearing and Seeing.”Quran, An-Nisaa’ verse 58
Postmortem biochemistry is usually performed by the
hospital autopsy pathologist, but it can be useful in a
forensic setting.
The pathologist should be aware of the value and
limitations of postmortem biochemistry because he will
inevitably encounter a number of cases that require
investigation into the decedent’s metabolic state.
Most of the previous studies were performed by
comparing premortem and postmortem fluids to show
which components remain relatively constant, which
undergo predictable change, and which are too altered
to be of diagnostic use.
Introduction
Carbohydrates and Related Metabolites.
Electrolytes and Trace Elements.
Nitrogenous Compounds.
Cholesterol and Other Lipids.
Proteins.
Bile Pigments and Other Indicators of Hepatic Function.
Hormones.
Studied Elements
1.Glucose.
2.Ketones.
3.Lactic Acid.
Carbohydrates and Related Metabolites
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
1.Glucose.
Carbohydrates and Related Metabolites
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
Hypoglycemia: (it is a normal postmortem
event) Postmortem Decrease & Possible Value:
1. Due to continuous consumption of glucose by
surviving cells postmortem, blood glucose levels
decrease rapidly.
2. Its level can decrease to ZERO after few hours.
3. A low glucose level in blood from the right atrium
and a positive test for ketones MAY support
starvation in the setting of abuse or neglect.
1.Glucose.
Carbohydrates and Related Metabolites
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
Hyperglycemia: (a level more than 200 mg/dL)
Limitations concerning sampling & Interpretation:
1. Sampling of vitreous fluid from the centre of both
eyes.
2. It is preferred to be sampled as soon as possible after
arrival at the morgue (loss of vitreous humor with low
temp.).
3. Immediate bedside analysis using a blood gas
instrument.
4. Standardized sampling containers must be used.
5. This level only indicates that the decedent had
uncontrolled diabetes.
1.Glucose.
Carbohydrates and Related Metabolites
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
Hyperglycemia: (a level more than 200 mg/dL)
Difficult interpretation & False Positive Results:
1. Death from asphyxia, cerebral hemorrhage, congestive
heart failure, electrocution, or terminal cardiopulmonary
resuscitation may increase postmortem peripheral
vascular glucose.
So, other causes of violence must be excluded by
autopsy.
2. Other investigations must be done as well: (i) glycosuria,
(ii) ketonuria, or (iii) elevated serum acetone level,
and (iv) blood level of glycosylated hemoglobin and
(v) glycosylated fructosamine to confirm diabetic
ketoacidosis.
2. Ketones & Lactic Acid.
Carbohydrates and Related Metabolites
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
Total ketone bodies (acetone, acetoacetate, and b-hydroxybutyrate): can be measured in PM blood, vitreous, pericardial fluid, and urine
interpretation of Results:
1. Serum lactic acid increases rapidly after death, and
antemortem levels are increased 20 times and 50 to 70
times at 1 and 24 hours, respectively.
2. Vitreous humor lactic acid increases from its initial
values of 80 to 160 mg/dL to 210 to 260 mg/dL 20 hours
after death.
3. Its value allow a quick determination of Possible
ketoacidosis.
1.Sodium, Chloride, and
Potassium.
2.Carbon Dioxide Content.
3.Calcium, Magnesium,
Phosphorus, and Sulfur.
4.Trace Elements.
Electrolytes and Trace Elements
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
1.Sodium, Chloride, and
Potassium.
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
Their PM blood concentration do not accurately reflect AM levels because of variable instability after death.
interpretation of Results:
1. Vitreous sodium (150 – 190 mEq/L) concentration remain
relatively stable in the early postmortem period.
2. Vitreous chloride (114 mEq/L) concentration remain
almost constant during the early 18 hours.
Electrolytes and Trace Elements
1.Sodium, Chloride, and
Potassium.
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
interpretation of Results:
3. The blood potassium level rises extremely rapidly after death as
cell membranes lose integrity. In vitreous, PM K+ levels rise
gradually (stable correlation phase), however, the margin of error
in these calculations is HIGH and vitreous K+ levels should not be
used to estimate time of death, due to many factors:
a. Possible AM electrolytes’ imbalance.
b. Metabolic diseases.
c. Environmental temperature (inappropriate conservation -
lower in cold weather).
d. The K+ rise is faster in infants> adults.
e. Inappropriate sampling (near retinal lining) false results.
f. Further clinical researches and case-studies are in process.
Electrolytes and Trace Elements
2. Carbon Dioxide. Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance: Postmortem vitreous carbon dioxide content averages
15 mEq/L (range 4 to 27 mEq/L) and remains relatively stable for at least 15 hours after death.
3. Calcium, Magnesium, Phosphorus, and Sulfur.
ML significance: of little use The serum Ca++ remains briefly stable and then rises
slowly. Initial vitreous calcium levels range from 6 to 8 mg/dL (1.5 to 2 mmol/L), and the values rise very slowly until decomposition ensues.
Mg++in vitreous humor rise slowly but erratically after death.
Inorganic and organic phosphorus levels increase quickly after death.
Sulfate levels are stable during the initial PM period.
Electrolytes and Trace Elements
1.Urea Nitrogen and Creatinine.
2.Other Nitrogenous
Compounds.
Nitrogenous Compounds
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
1. Urea Nitrogen & Creatinine. Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML significance:Postmortem Urea nitrogen & creatinine are perhaps the most stable blood constituent following death as it approximates premortem levels, even after moderate decomposition.
Nitrogenous Compounds
These patterns can indicate child neglect, homicide, septicemia, SIDS, alcoholism, or prolonged diuretic therapy.
Creatinine is a valid postmortem marker of nitrogen retention and renal function.
2. Other Nitrogenous Compounds. Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance:
Nitrogenous Compounds
All these compounds increase after death.
PM ammonia levels in vitreous humor increase linearly –
during the first 24 hours.
Although relatively stable after death, uric acid levels are
higher in blood samples from the right side of the heart
than from left heart or periphery. Postmortem
hyperuricemia may also be elevated after death caused by
asphyxiation or drowning, but further studies of this finding
are required.
concentrations of ammonia, amino acids, glutamine,creatine, and oxypurines (uric acid, xanthine, and hypoxanthine)
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance:
Cholesterol and Other Lipids
Postmortem serum total cholesterol used to identify
familial hypercholesterolemia.
Correlation of PM serum lipid levels with AM state is difficult:
1. The decedent may not have been in a fasting state
at the time of death.
2. Familial hyperlipoproteinemias have been identified
from postmortem studies.
3. Elevated levels of postmortem lipids in serum and
other fluids have been associated with the presence
of coronary heart disease and sudden cardiac
death.
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance:
Proteins
Albumin/Globulin ratio: PM studies show that the values for
total proteins and ratio are similar to those of AM
specimens.
1. Provided that there is minimal hemolysis, serum
electrophoresis has been useful in the postmortem
diagnosis of agammaglobulinemia, monoclonal
gammopathy, and hemoglobinopathies .
2. Total immunoglobulin E (IgE) is elevated in some cases
of fatal asthma.
3. Specific IgE antibodies in postmortem serum may help
corroborate the diagnosis of anaphylaxis following
insect stings or ingestion of allergenic food.
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance:
Proteins
C-reactive protein: PM Postmortem measurement of in the
blood or liver (if blood is not available):
1. If marked elevation and in case of doubt of minimal
injury: it may indicate a natural mode of death in
decedents.
2. In those with obvious trauma, it suggests a vital
reaction.
CRP levels were independent of the post-mortem interval.
CRP is stable for 1 month PM (easy, viable, inexpensive).
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance:
Proteins
Enzymes:
1. Elevated levels of creatine kinase, lactic dehydrogenase, and their isozymes in pericardial fluid and serum have been correlated with myocardial injury related to trauma or the early stages of myocardial infarcts.
2. Myosin concentration was a better indicator of widespread cardiac muscle damage.
3. Postmortem pericardial levels of cardiac troponin I greater than 40 ng/mL (better combined with troponin T) correlated closely with pericardial concentrations of myoglobin, with elevated troponin levels supporting a diagnosis of cardiac injury (the highest level was in acute MI).
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance:
Proteins
Enzymes:
4. Mast cell tryptase (combined assay for a- and b-
tryptase) has been used to detect anaphylactic reactions (NOT-specific elevated in other conditions, including coronary artery thrombosis, heroin injection, sudden infant death syndrome, amniotic fluid embolism, and asphyxia).
To increase accuracy, MAY be combined with:(1) accurate medical history (particularly atopic
disposition of the decedent and temporal relationship of possible allergen exposure and death).
(2) findings at autopsy, total IgE levels, and, (3) if possible, analysis of relevant IgE antibodies.(4) A peripheral blood is better (heart blood contains
more elevated levels of tryptases).
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML Significance:
Bile Pigments & Indicators of Hepatic Fn.
Serum Bilirubin : increase slowly after death but allow determination of the extent of antemortem jaundice; however, minimal elevations of postmortem bilirubin are difficult to interpret.
Urobilinogen remains stable in the urine but diffuses from blood to CSF whenever the blood level is high.
MILD liver dysfunction cannot be readily assessed using postmortem chemical analysis because the enzymes used to assess liver function become elevated after death, BUT, total cholesterol + low serum protein levels with inversion of the albumin/globulin ratio + high serum bilirubin level + and the presence of abnormal levels of bile and urobilinogen in the urine CONFIRM SEVERE liver damage.
Elevation of glutamine level in the postmortem CSF samples CORRELATES with Hepatic Coma.
Carbohydra
tes and
Related
Metabolites.
Electrolytes
and Trace
Elements.
Nitrogenous
Compounds
.
Cholesterol
and Other
Lipids.
Proteins.
Bile
Pigments
and Other
Indicators
of Hepatic
Function.
Hormones.
ML significance:
Serum cortisol, parathormone, chorionic gonadotropin, thyroid-stimulating hormone, and luteinizing hormone concentrations remain stable in the early postmortem period.
Insulin Poisoning (suicide and homicide): Serum insulin is extremely difficult to measure accurately because it degrades rapidly at room temperature.
Diagnosis can be made as follows:
1. Peripheral blood samples should be collected in tubes
containing sodium fluoride or ethylenediaminetetraacetic
acid (EDTA).
2. Serum should be separated from red blood cells as soon as
possible
3. Samples should be refrigerated or, preferably, frozen.
4. Elevated PM blood INSULIN.
5. Low blood C Peptide (a diagnosis of exogenous insulin
overdose).
6. In postmortem blood, C peptide is more stable than insulin,
although collections still require special handling: collection
in heparinized tubes, separation of plasma, and, without
delay, storage of the serum sample in a freezer.
Hormones
Interpretation of biochemical results must be done with great caution & on an individual case by case basis.
High selection of suspected and criminal cases is a necessity, rather than wasting efforts, time and costs in
revealing cause of death in normal natural deaths.
Re-evaluation and unifying toxicological and histopathological investigations through providing
experienced professionals in these fields, extensive scientific cooperation including immunostaning studies for histopathology and sharing thoughts and plans for
better achievement with these departments.
Group meeting and workshops are needed with the related laboratories to study further cooperation, feasibility
studies, and cost effectiveness of these sophisticated investigations in specific kinds of medicolegal cases.
Conclusion & Recommendations
Thank You
Mamdouh K. Zaki
Thank You
Mamdouh K. Zaki