Acidemia is defined as arterial pH <7.35 or venous pH <7.3. A venous pH <7.3 or a serum HCO3- <15 mEq/L is used in medical practice to confirm the diagnosis of a diabetic ketoacidosis (with lower values of both indicating greater severity of the medical condition). During the initial evaluation, venous blood pH is frequently used to make the diagnosis and classify the severity of ketoacidosis. The serum bicarbonate (HCO3-) concentration alone is also a simple and accurate predictor of ketoacidosis and its severity. Serum HCO3- concentration can be used in lieu of venous pH, especially in resource poor settings (i.e., where access to pH measurement is limited). Venous pH <7.1 or a serum HCO3- <10.5 mEq/L has been used to define severe ketoacidosis in patients with diabetes. In adults, venous HCO3- concentrations predict arterial pH with a higher degree of sensitivity and specificity.
Calcium, the king of minerals is the fifth most common element and the most prevalent cation found in the body. Calcium has a very important role to play in skeletal mineralization, blood coagulation, neuromuscular conduction, maintenance of normal tone and excitability of skeletal and cardiac muscle, stimulus secretion of exocrine glands and preservation of cell membrane integrity and permeability. In the extracellular fluid, approximately 50% of calcium exists as ionized (i.e., free and physiologically active), while 40% is protein bound (mainly to albumin, and to a lesser extent globulins). 10% is bound to anions (e.g., bicarbonate, citrate, lactate and phosphate). Because calcium is predominantly transported bound to serum proteins, total calcium (TCa) levels are greatly influenced by protein concentration. Albumin (ALB) is the principal transport and depot protein for calcium in blood plasma.
Conditions resulting in hypoalbuminemia will decrease total calcium (TCa), while ionized calcium (Ca2+) is generally unaffected by changes in albumin concentration. The debate about adjusting calcium for albumin has been continuing ever since the initial description of the relationship between total calcium (TCa) and albumin was published. Albumin-adjusted, or corrected calcium, is the estimation of the expected total calcium (TCa) level if the albumin were normal. Portale’s formula is applicable for this calculation. Under most circumstances, unadjusted total calcium would be a reasonable initial test in assessing the patient’s calcium status. Although ionized calcium (Ca2+) would be ideal, given that it is the physiologically-relevant marker of calcium status, and is unaffected by variations in albumin, the value fluctuates with pH, which may alter when the sample is in transit, or if analysis is delayed.
Magnesium is the fourth most prevalent and second most abundant intracellular cation. Magnesium plays a fundamental role in many functions of the cell, including energy transfer, storage and metabolism, maintenance of normal cell membrane function, and the regulation of parathyroid hormone secretion. Systemically, magnesium lowers blood pressure and alters peripheral vascular resistance. Magnesium is involved in nearly every aspect of biochemical metabolism, activates almost all enzymes involved in phosphorus reactions and acts as a molecular stabilizer of ribonucleic acids. Only 1% of the total magnesium found in the body accounts for the extracellular fraction. Of the circulating magnesium, approximately 15% is bound to anions such as phosphate and citrate, 30% is complexed with protein such as albumin, and the other 55% remains unbound.
Assessment of kidney function has for decades been based on serum creatinine concentration, which is an inexpensive, common test in medical practice. Serum or plasma creatinine is quite an inaccurate test for estimating kidney function because creatinine (CREA) begins to rise only when the glomerular filtration rate (GFR) has diminished by one half, and thereafter the rise is exponential and not linear to GFR deterioration. Serum creatinine concentration is also affected by age, sex, muscle mass or breakdown, diet, race, tubular secretion, drugs (e.g., amiloride, triamterene, spironolactone, trimethoprim) and laboratory analytical methods. Given that clearance of substances only occurs in the lean tissues, perhaps the lean body mass (LBM) may serve as a better estimate in obese patients (BMI ≥30 kg/m2).
Pre-renal failure, also called pre-renal azotemia, is described as a reversible increase in serum creatinine and urea concentrations resulting from decreased renal perfusion, which leads to a reduction in the glomerular filtration rate (GFR). Approximately a half of hospital patients with acute kidney injury have BUN / creatinine ratio >20. The reason for this lies in the mechanism of filtration of BUN and creatinine (i.e., renal plasma flow is decreased due to hypoperfusion which results in a proportional decrease in GFR). During gastrointestinal bleeding, hemoglobin is broken down by digestive enzymes into amino acids which are reabsorbed. Because urea is the end product of protein metabolism, BUN is disproportionately elevated relative to serum creatinine. BUN reabsorption is also increased.
Inflammation is a body defense mechanism in response to harmful stimuli. It is an essential component of normal tissue homeostasis. After tissue injury, the inflammatory cells (neutrophils and monocytes/macrophages) secrete cytokines into the bloodstream, stimulating hepatocytes to produce proteins, which are directly involved in the body’s defense mechanisms. These are known as acute phase proteins, and their plasma levels can be modulated rapidly at the onset of inflammation. Variations of acute phase protein serum levels have been studied in many diseases, such as type 2 diabetes, Alzheimer’s disease, the risk of Parkinson’s disease, the evolution of cancers and in cases of bacterial infections. There is increasing evidence that inflammatory responses contribute to host defense during the evolution of infectious diseases by acting as part of the innate immune system. C-reactive protein (CRP) is an acute phase protein that serves as an early marker of inflammation or infection. CRP is synthesized in the liver and is normally found at concentrations of <10 mg/L in the blood.
During infectious–inflammatory disease states, C-reactive protein (CRP) levels rise rapidly within the first 6 to 8 hours, then peak to levels of up to 350 – 400 mg/L after 48 hours. CRP binds to phosphocholine expressed on the surface of damaged cells, as well as to polysaccharides and Peptosaccharides present on bacteria, parasites and fungi. This binding activates the classical complement cascade of the immune system and modulates the activity of phagocytic cells, supporting the role of CRP in the opsonization (i.e., the process by which a pathogen is marked for ingestion and destruction by a phagocyte) of infectious agents, and the dead or dying cells. When the inflammation or tissue destruction is resolved, CRP levels fall, making it a useful marker for monitoring disease activity. Recent awareness of the utility of measuring CRP as a risk factor for cardiovascular disease has led to the development of high-sensitivity CRP (hs-CRP) assays to detect lower levels of CRP (0.5 – 10 mg/L). CRP levels are unaffected by anemia, protein levels, red blood cell shape, patient age or sex. CRP concentrations tend to be higher late in pregnancy.