Metabolic Information and Courses from MediaLab, Inc.

Due to the wide range in urine pH values in healthy individuals, pH results must be evaluated in conjunction with the patient's medical condition. Factors to be considered include: respiratory or metabolic acidosis respiratory or metabolic alkalosis renal function crystal or calculi formation urinary tract status diet

Although glucose is the sugar most commonly tested for in urine, normal human urine can contain small amounts of galactose, lactose, fructose, xylose, and other pentoses. Galactosuria, an abnormal amount of galactose in the urine, occurs in infants with a congenital metabolic defect. Lactose may be found in the urine of nursing women and during late pregnancy. All of these sugars, including glucose, are reducing substances.

We are all aware of the clinical laboratory's role in assessing overall health and we are also aware that measuring a patient's serum lipids will provide some insight into their cardiovascular health. The traditional measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides are the 'classic' cardiovascular risk markers.Laboratorians, and even the general public are now well-aware that LDL-C ('bad' cholesterol) concentrations should be low while HDL-C ('good' cholesterol) concentrations should be high. Triglycerides should be kept in check as well. Optimal levels are shown in the table below. So what is the risk if these values are not within optimal ranges?Cardiovascular risk can be simply defined as increasing the odds of having a pathology which affects blood flow and/or the heart. The most common cardiovascular pathology is atherosclerosis. Other cardiovascular pathologies whose odds increase as serum lipids and other cardiovascular markers become suboptimal are myocardial infarction (heart attack), stroke, congestive heart disease and coronary artery disease. Other diseases such as diabetes and the metabolic syndrome are also strongly associated with the classic cardiovascular risk markers LDL-C, HDL-C and triglycerides.

Free radicals are well known to occur in biological systems. A free radical is an atom or small molecule with unpaired electrons. These unpaired electrons make the atom or molecule highly reactive and unstable. Free radicals are produced constantly via metabolic processes. They are also released by immune cells. Immune cells can undergo 'oxidative bursts' (also called respiratory bursts) to help fight pathogens. Oxidative bursts can help degrade pathogens phagocytosed by immune cells and therefore free radicals have an important role in immune system function.However, free radicals also have detrimental effects on surrounding cells. When LDL is co-localized with cells or tissues that are releasing free radicals (such as in an inflamed vessel wall) the free radicals can chemically modify the phospholipids and other components of the lipoprotein. The LDL becomes oxidized and the modification makes the LDL more atherogenic.

As we will discover later in the course, there are other variables which impact the effectiveness of hemostatic mechanisms as well, such as acquired disease states, and inborn metabolic pathway defects. For now, however, our focus will be on the mechanisms, processes, and components which work together to achieve coagulation, or the cessation of blood flow from a damaged vessel. Note: The terms coagulation and hemostasis are used interchangeably throughout this course.

Because hereditary hemochromatosis (HH) is a disease of iron overload, a review of the basic principles of iron metabolism is helpful in understanding its pathophysiology. Iron is needed by all body cells and is crucial for oxygen transport, oxidative metabolism, and cell growth and proliferation. To serve these functions, iron must be bound to protein. Iron is potentially harmful when ionized or complexed to inorganic compounds. Iron must be present in amounts sufficient to carry out these normal functions, but not in excessive amounts which may be toxic.Two types of iron-containing compounds are normally found in the body: compounds that serve in metabolic or enzymatic functions and storage compounds. Hemoglobin, myoglobin, cytochromes and other proteins are involved in oxygen transport and utilization. Iron in hemoglobin comprises about 67% of total body iron, thus erythrocytes are rich in iron. Approximately 27% of iron is found in storage compounds. Myoglobin, other tissue iron, and transport iron comprise the remaining 6% of total body iron. (2)

When discussing PGx, we classify a person according to his/her phenotype (metabolic capacity for a given enzyme).A poor metabolizer (PM) is a person who lacks the functional enzyme and therefore exhibits decreased metabolism of drugs. This person would require lower doses of a drug that is metabolized by that enzyme. A PM who receives a standard dose is more likely to experience unwanted side effects or toxicity. A PM can also experience diminished effects with drugs that need to be metabolized to active compounds by the enzyme in question.An ultrarapid metabolizer (UM) will require a higher dose than usual since he/she will eliminate the drug more quickly. A UM may be resistant to standard treatments, and it may take some time to adjust the dosage before therapy is achieved.An intermediate metabolizer (IM) has one wild-type (normal) copy of the gene and one absent or dysfunctional copy. The IM group is very heterogeneous.A person with normal enzyme activity is referred to as an extensive metabolizer (EM). This person should respond to standard dosages of a drug. Most people are EM's. This is the population in which most dosing regimens have been worked out in clinical trials.

Phenotyping involves measuring the metabolism of a probe drug. For example, with CYP2D6, dextromethorphan or debrisoquine can be given to a patient to see how well the drug is metabolized. Both these drugs are safe and extensively metabolized by CYP2D6. By measuring the parent drug and the metabolite in urine, the metabolic capacity of a CYP450 enzyme can be estimated. Such testing is complex and tedious, however, and has not become routine in clinical laboratories. Therefore, genotyping is likely to be the main tool that is used for assessing the PGx of a patient.

Consists of an electrolyte panel, plus: Blood urea nitrogen (BUN), which a measure of renal function. Creatinine (Creat), which also measures renal function Glucose, the most important blood sugar, and Calcium. Run on serum or plasma

These are some of the panels you will frequently encounter: Hemogram (CBC)Electrolytes (Lytes) Basic Metabolic Profile (BMP)Comprehensive Metabolic Profile (CMP)

Echinocyte comes from the Greek word meaning “sea urchin,” which relates to its shell-like appearance. Echinocytes, more commonly referred to as burr cells, are reversible, meaning that this alteration can be the result of the cell’s environment, pH of the medium (including the glass slides on which blood smears are made), the metabolic state of the cell and the use of some chemical substances. Several echinocytes (burr cell) can be seen in this slide; three of them are indicated by the arrows. Notice that the projections are rounded and evenly spaced around the cell. Acanthocytes, by contrast, have irregularly spaced thorn-like projections.

Crystals are not usually present in freshly voided urine, but can appear in urine left at room temperature for several hours. Most crystals form due to changes in urine pH and temperature after collection. Diagnostically significant crystals may indicate the presence of a metabolic disorder, renal calculi formation, or provide information that can be used to regulate medications.