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Diagnostic Chemicals In Human Body Fluids - The PjProblemStrings.
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Diagnostic Chemicals In Human Body Fluids - The PjProblemStrings.

The construction of the human body is based on a primordial equilibrium (an initial health state). The human body is mostly fluids. Consequently, human body fluids play important roles in the determination of human health.

(a) What is meant by human body fluid?
(b) What are some of the important diagnostic chemicals in human body fluids?
(c) How are diagnostic chemicals in human body fluids measured?
(d) Use PjProblemStrings to summarize the reasons for measuring
diagnostic chemicals in human body fluids.

The strings: S₇P₁A₁₆ (Containership - Density).

The math:
Pj Problem of Interest is of type Containership (Density). The amount of diagnostic chemicals in human body fluids is the measurement of interest and is often expressed as mass/volume (density).



(a) The human body fluid refers to the fluid part of the body. It is more than two third of the whole body and is roughly forty litres (40L) in an apparently healthy adult. Water is the major constituent of the human body fluid.
The human body fluid is distributed into two major compartments in the body: the intracellular fluid (ICF) and the extracellular fluid (ECF).

The ICF is the fluid found in the cells of the body (about 22L in an apparently healthy adult).

The ECF is the fluid found outside the cells of the body and it includes intravascular fluid (plasma), interstitial fluid, lymph, fluid in bones, fluid in dense connective tissues like cartilage, cerebrospinal fluid, intraocular fluid, digestive juices, serous fluid (intrapleural, pericardial and peritoneal fluid), synovial fluid in joints and fluid in the urinary tract.

The volume of the interstitial fluid is about 12L. The volume of the plasma is about 2.75L while the volume of the other subunits of the ECF is about 3.25L.

(b) The human body is made up of chemicals (atoms, molecules and compounds of some of the elements of the periodic table).
The most prominent elements are: oxygen (61% of body mass), carbon (23%), hydrogen (10%), nitrogen (2.6%), calcium (1.4%), phosphorus (1.1%), sulfur (0.2%), potassium (0.2%), sodium (0.14%), chlorine (0.12%), magnesium (0.027%; 270 p.p.m), silicon (0.026%; 260 p.p.m), iron (60 p.p.m), fluorine (37 p.p.m), zinc (33 p.p.m), copper (1 p.p.m), manganese (0.2 p.p.m), tin (0.2 p.p.m), iodine (0.2 p.p.m), nickel (0.1 p.p.m), molybdenum (0.1 p.p.m), vanadium (0.1 p.p.m), chromium (0.03 p.p.m), cobalt (0.02 p.p.m). Ions and compounds of these chemicals consititute the diagnostic chemicals in human body fluid. Some important diagnostic chemicals in human body fluids are as follows:

Creatinine
Normal range:
Male: 0.7 to 1.4 mg/dl
Female: 0.4 to 1.2 mg/dl
Creatinine is a non protein nitrogenous waste product that is formed from the metabolism of creatine in the skeletal muscles. Creatine is a molecule of major importance for energy production in muscles. It is synthesized primarily in the liver and transported to the muscles where it is converted to creatinine. Creatinine diffuses freely into the extracellular fluid (ECF). The kidneys then filter the creatinine from the ECF and excrete it in the urine. The excretion of creatinine is relatively constant in the absence of disease, and it is proportional to an individual's muscle mass.

Measurement of serum or plasma creatinine concentration is used to determine the sufficiency of kidney function, the severity of kidney damage and to monitor the progression of kidney disease.

Possible diagnostic inferences when plasma creatinine concentration is higher than the normal range
- Glomerulonephritis (inflammation of the glomerulus)
- Pyelonephritis (inflammation of the pelvis)
- Renal tuberculosis
- Disease causing obstruction of urine flow
- Acute renal failure
Probable diagnostic inference when plasma creatinine concentration is lower than the normal range
(1) Muscle wasting

Uric acid
Normal range:
Male: 3.5 to 7.2 mg/dL
Female: 2.6 to 6.0 mg/dL
Uric acid is the final product resulting from the catabolism of purine. Purines such as adenosine and guanine result from the breakdown of nucleic acids or from the destruction of tissue cells, and are converted primarily in the liver into uric acid. From the liver, the uric acid is transported in the plasma to the kidney, where it is filtered by the glomerulus into the renal tubules. About 98% to 100% of the filtered uric acid is reabsorbed in the proximal tubules, and small amount of the uric acid is secreted by the distal tubules into the urine. Renal excretion accounts for about 70% of uric acid elimination, the remainder is excreted through the gastrointestinal tract (GIT).

Uric acid is measured to assess inherited disorders of purine metabolism, to confirm diagnosis and monitor treatment of gout, to assist in the diagnosis of renal calculi, to prevent uric acid nephropathy during chemotherapeutic treatment, and to detect kidney dysfunction.

Possible diagnostic inferences when plasma concentration of uric acid is higher than the normal range
- Gout
- Excessive dietary purines such as liver, kidney, legumes etc.
- Cytotoxic treatment of malignancies such as leukaemias and lymphomas.
- Polycythaemia
- Multiple myeloma
- Sickle cell anaemia
Possible diagnostic inferences when plasma concentration of uric acid is lower than the normal range
- Alcohol ingestion
- Ketoacidosis
- Lactic acidosis
- Renal dysfunction

Blood Urea Nitrogen (BUN). Normal range: 7 - 20 mg/dL
Blood Urea Nitrogen is a measure of the amount of urea nitrogen in the blood. Nitrogen in the form of ammonia (NH₃) is a by product of the breakdown of non-storable protein into amino acids in the liver. Since ammonia is toxic, the liver converts it into urea [(NH₂)₂CO]. The blood transports urea from the liver to the kidney where it is filtered and flushed from the body.
Elevated BUN may suggest kidney malfunction.

Albumin. Normal range: 3.9 - 5.0 g/dL.
Albumin is a small protein made in the liver. Albumin is the most abundant protein in blood serum and it helps in nourishing tissues and the transport of hydrophobic substances (hormones, fats, etc). Albumin plays an important role in the maintenance of colloid osmotic pressure at the venule ends of capillaries. Capillary presure causes fluid and dissolved substances to move from the arteriole ends of capillaries into interstitial spaces. Osmotic pressure causes fluids to move from interstitial spaces into blood plasma thus preventing significant fliud retention (edema) in interstitial spaces.
A variety of medical conditions may cause low amount of albumin in blood plasma. For example, malnutrition and chronic liver disease may cause low amount of albumin.

Globulin
Globulin is a group of proteins that comprises enzymes, antibodies and many other proteins. The combined amount of Albumin and Globulin in the blood gives an estimate of total blood protein. Albumin to Globulin ratio is also often measured. Total blood protein outside the normal range (6.3 - 7.9 g/dL) may suggest liver and kidney dysfunctions, and malnutrition.

Bilirubin.Normal range: 0.2 - 1.9 mg/dL.
Bilirubin is a yellow-brown waste product from the breakdown of old red blood cells by the liver. Macrophages in the liver, spleen and bone marrow engulf and break down old red blood cells: Hemoglobin is disintegrated into Heme and Globin(a protein). Globin is then broken into reusable amino acids. Heme is de-ironed and the iron is reused in erythropoiesis. The de-ironed Heme is converted into biliverdin (a green pigment), then to bilirubin (yellow color). The liver then excretes most of the bilirubin into bile from where it enters the duodenum, small and large intestines and later excreted in stool. Bile not excreted by the liver is excreted by the kidneys. Bilirubin and its urobillins (derivatives of bilirubin) give urine its yellow color. Bilirubin that has been worked on by intestinal bacteria give feces its brownish color.
Elevated level of bilirubin in blood plasma causes jaundice (skin and whites of the eyes turn yellow) and may suggest liver dysfunction and or dysfunction in its excretion processing. White or clay color stool may also suggest such dysfunctions.

Liver enzymes: enzymes are proteins that are chemical catalysts in various biochemical processes in the human body. Alkaline Phosphatase (ALP normal range: 44 -147 international units/liter) , Alanine Transaminase (ALT normal range: 8 - 37 international units/liter) and Aspartate Aminotransferase (AST normal range: 10 - 34 international units/liter) are some liver enzymes which may suggest liver disease when they are present in elevated amounts in the blood.

Electrolytes
Electrolytes are ions in human body fluids: sodium ions(Na+, normal range:136-144 mEq/L, milliequivalent/Liter), potassium ions (K+, normal range:2.7-5.2 mEq/L), calcium ions (Ca²⁺, 8.5-10.9 g/dL) and chloride ions (Cl-, 101-111 mmol/L, millimoles/Liter). The hormone, aldosterone help control sodium and potassium concentration in body fluids while the parathyroid hormone help control calcium concentration. These electrolytes, in general, help to regulate water and PH balance in the body, proper functioning of the nervous system, muscles, heart, kidneys and lungs. Abnormal amounts of these electrolytes in blood may suggest dysfunctions in bodily processes. Included in the electrolytes tests is the measurement of the amount of carbon dioxide (CO₂), bicarbonate (HCO₃-) and carbonic acid (H₂CO₃) in the blood. They also help with blood PH balance and charge balance in cells. Carbon dioxide concetration is maintained by the lungs and kidneys. Abnormal concentrations may suggest lung and kidney dysfunctions.

Lipids
Cholesterol: are fatty substances that are usually the focus of lipid tests. They circulate in the body in complex molecules called lipoproteins. Two types of lipoproteins are of interest: Low Density Lipoprotein (LDL) and High Density Lipoprotein(HDL).
Low Density Lipoprotein (LDL): this cholesterol is nicknamed bad cholesterol because they can clog arteries with the excess cholesterol they deposit in arterial walls. These cholesterol deposits can burden the heart because they restrict blood flow in arteries (atherosclerosis). Cadiac arrest (heart attack) and stroke may result. LDL level less than 100 mg/dL (milligrams/deciliters) desirable.
High Density Lipoprotein (HDL): this cholesterol is nicknamed good cholesterol because they help to transport cholesterol to the liver where it is processed for excretion. HDL greater than 40 mg/dL desirable.
Total cholesterol: less than 200 mg/dL desirable.
Triglycerides: are fats. They result from the conversion of energy from food that is not immediately needed for work. Elevated amount also impairs cardiovascular functions. Low levels (100 -150 mg/dL) desirable.

Blood Glucose
Normal range:
Fasting blood glucose: 60 to 110 mg/dl
Random blood glucose: 75 to 120 mg/dl
Glucose is a monosaccharide (simple sugar). Glucose is the main end product of carbohydrate digestion and it provides energy for life processes. Glucose is absorbed from the small intestine into the blood stream after the ingested carbohydrate has been digested by the various enzymes. Depending on the energy need of the body, the absorbed glucose can either be transported to the cells of the body where it is oxidized to provide the chemical energy needed for cellular activities, or transported to the liver and skeletal muscles where it is converted to glycogen by the process called glycogenesis. The liver glycogen is converted back to glucose by the process called glycogenolysis when the need arises to maintain the blood glucose level. Muscle glycogen provides the glucose for muscular activities. Excess glucose is converted to fatty acids and stored as fats in the adipose tissues. If needed, glucose can be formed from fats and proteins (gluconeogenesis), and this results in the production of ketones. The concentration of glucose in the blood is primarily controlled by the hormones insulin and glucagon. However, other hormones (adrenaline, growth hormone, adrenocorticotropic hormone (ACTH), corticosteroid hormone and thyroxine) play some roles in the control system. Plasma or blood glucose is measured mainly in the diagnosis and management of diabetes mellitus.

Possible diagnostic inferences when plasma glucose concentration is higher than the normal range (hyperglycemia)
Severe hyperglycemia
- Diabetes mellitus
- Adrenal cortical hyperactivity (Cushing's syndrome)
- Acromegaly
- Obesity
Mild hyperglycemia
- Severe liver disease
- Pancreas disorder
- Pituitary disorder
- Steroid therapy
- Acute stress reaction (physical or emotional)
- Convulsion
Possible diagnostic inferences when plasma glucose concentration is lower than the normal range
Severe hypoglycemia
- Insulinoma
- Hypopituitarism
- Ectopic insulin production from tumours
- Adrenal cortical insufficiency
Mild hypoglycemia
- Acute alcohol ingestion
- Severe liver disease
- Glycogen storage disorder
- Hereditary fructose intolerance
- Kwashiorkor (malnutrition)
- Addison's disease

(c) Chemicals in human body fluids are measured for various reasons and there are various measurement protocols. However, much of the measurements relate to the process of determining the health state of the human body. Diagnostic chemicals in human body fluids are measured inorder to determine if their amounts in the body fluids are consistent with the normal amounts present in the body fluids of a healthy human body. The measurement protocol of interest is the Chemistry Panel or Screen (also called the Comprehensive Metabolic Panel). The Chemistry Panel usually consists of about 20 tests that determine the amounts of diagnostic chemicals in blood and urine. Abnormal amounts of the diagnostic chemicals may suggest dysfunctions of the kidneys, liver, the cardiovascular system and the body's metabolism.

Samples of blood and urine are drawn from the body. Fasting tests require that there should be no food intake 8 - 10 hours before test. Then, Automated analyzers (clinical chemistry analyzers) are used to carry out the measurements.
Photometry is a method frequently used to measure the concentrations of diagnostic chemicals in human body fluids. In this method, the sample is mixed with the appropriate reagent. The reaction produces a color. The concentration of the chemical of interest in the sample (analyte) determines the strength of the color produced. The spectrophotometer (a device capable of emitting electromagnetive waves) measures the amount of light absorbed when it shines light of appropriate wavelength at the sample. The amount of light absorbed is then directly correlated with the concentration of the analyte in the sample. The principle of the spectrophotometer is based on Beer-Lambert's law:

The amount of light absorbed by a solution, when illuminated with a light of suitable wavelength, is directly proportional to the concentration of the solution and the length of the light path through the solution. That is, the more concentrated a solution is, the more the amount of light it will absorbed and the lesser the amount of light that will be transmitted. In mathematical terms:
A = KCL -----------> (1)
Where A = absorbance
K = wavelength -dependent absorptivity coefficient
C = Concentration of analyte
L = length of light path through solution

To measure the concentration of a diagnostic chemical in the human body fluid, the spectrophotometer first measures the absorbance of a standard solution (a solution whose concentration is known) and the absorbance of the analyte.
By the proportionality established by equation (1):
C_a = [A_a x C_s]/A_s, where:
C_a = concentration of analyte
C_s = concentration of standard solution
A_a = absorbance of analyte
A_s = absorbance of standard solution.

Often experimental measurements are made in terms of transmittance (T).
Where T = I_t/I_o
I_o = intensity of initial light
I_t = intensity of transmitted light
The relation between absorbance (A) and transmittance (T):
A = -logT = -log(I_t/I_o).

In general, when a beam of incident light of intensity I_o passes through a solution, a part of the incident light is reflected I_r, a part is absorbed I_a and the rest is transmitted I_t.
So, I_o = I_r + I_a + I_t.

The Ion Seletive Electrodes (ISE) method is frequently used to measure the concentration of ions in a fluid sample. ISE (a sensor) determines the concentration of ions in a solution by measuring the current flow through an ion selective membrane.

(d) Fundamentally, dynamic primordial equilibrium is established in the human body at creation. This equilibrium initialized the body's health state. Associated with this equilibrium are the identities of the chemicals that constitute the human body.
PjProblemStrings: S₇P₇A₇₂ (dynamic equilibrium), S₇P₂A₂₁ (physical identity), S₇P₂A₂₂ (chemical identity).

Over time, the human body changes. Change may be gradual (e.g. aging) or immediate (e.g. trauma).
PjProblemStrings: S₇P₅A₅₁ (physical change), S₇P₅A₅₂ (chemical change).

Measuring the amounts of diagnostic chemicals in a given volume of human body fluids is a containership problem. Specifically, a concentration or density measurement.
PjProblemStrings: S₇P₁A₁₆ (containership - density).

The comparison of measured concentration of diagnostic chemicals in human body fluids [(S₇P₁A₁₆)_measured] to their normal values [(S₇P₁A₁₆)_normal] is the reason for their measurement.

When (S₇P₁A₁₆)_measured is different from (S₇P₁A₁₆)_normal, S₇P₅A₅₁ and or S₇P₅A₅₂ is established and problem with S₇P₇A₇₂ is suggested.

Math

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