Parameter values of hemogram components are based on worldwide averages that consider standard deviation as part of the formula when determining what is considered normal or abnormal readings of various important blood elements. Still, none of the below parameters are considered ‘universally’ normal; their values can range from lab to lab, although minimally.
In this article, we will list the most important biochemical items of interest for interpretation when contextualizing a hemogram with patient information and anamnesis.
Quantitative and qualitative analysis of blood cells further provide concrete diagnostic information (as covered in the article titled “Understanding the Cellular Components of a Blood Test”), but this article will focus solely on the biochemistry side of a hemogram, which allows physicians to diagnose, monitor, and prevent many diseases of physiological dysfunction. Some types of diabetes, for example, can be diagnosed based on glycemia and insulinemia alone, where morphological observations of the cell are not always necessary, unless of course the patient is also suffering from a condition that influences that aspect of a hemogram. Biochemical factors and cellular analyses can certainly be used to complement each other when attempting to diagnose certain diseases where a binary role between cell quantity/morphology and biochemical factors interact with each other; after all, many conditions can be duplicitous in nature, but it simply depends on the condition.
Urea – Blood Urea Nitrogen (BUN)
A crucial factor for renal scrutiny, urea is the final waste yield of protein metabolism and are filtered through the urinary system for excretion. A nitrogenous compound, urea is found in large quantities in urine (hence, the name) and stool. Normal urea levels in the blood are considered to be between 5-20 mg/dl.1 They are produced in the liver by using ammonia as a building block (derived from the metabolism of protein or amino acids) after which urea is created and released into the bloodstream for transportation to the kidneys, where it filters through glomeruli to join water and other metabolic waste to form urine.2 With this said, not all urea is eliminated, approximately 30% – 50% is reabsorbed by the renal tubules in the nephron during states of hypoperfusion. The purpose of reabsorbed urea is regulation of osmolarity and perhaps even as a source of amino acid synthesis (with the aid of bacterial flora in the gut) as proposed by Rose and Dekker.3
But what happens if blood urea levels are too high? In general, it can occur in 2 ways; either there is an increase of creatine phosphate catabolism and therefore elevated amounts of urea are found (high protein diet, for example), or because the urinary system is having difficulties in ridding the body of excess nitrogenous compounds.4 From this perspective, we can refer to uremia (high levels of urea) or hyperazotemia (high levels of urea and other nitrogenous compounds) as renal or non-renal related.
Causes of uremia include
- Renal failure
- Hepatic failure
- High protein diet
- High blood pressure
- Polycystic kidney disease
- Autoimmune diseases
- Certain medications
Dialysis treatment is considered the best option when severe uremia has manifested symptoms and signs reflective of the degree of affectation, including hyperkalemia, nausea, vomiting, acidosis, muscle cramps, weight loss, loss of appetite, fatigue, and a loss of interest and motivation in general. However, nothing can beat the natural kidney.5 Per Brent Alper Jr., MD:
“The ultimate treatment for uremia is dialysis. Initiation of dialysis is indicated when signs or symptoms of uremia are present and are not treatable by other medical means. Patients with uremia must have dialysis initiated as soon as symptoms appear, regardless of the glomerular filtration rate (GFR). Unfortunately, although dialysis effectively removes urea, it is less effective than the normal kidney at removing a number of toxic solutes, the accumulation of which is thought to lead to signs and symptoms that have been labeled residual syndrome.”6
Before any treatment is started, the underlying cause would of course need to be determined in order to proceed with the most appropriate method of fighting the condition.
Low urea levels are almost never a cause for concern, however, it can be an indicator of a serious liver disease or malnutrition.
Creatinine is the waste product of phosphocreatine (derived from creatine) metabolism from regular muscle wear and tear. Normal values range between 0.9 – 1.3 mg/dL in men, and 0.6 – 1.1 mg/dL in women. 7
Creatine is naturally created in the liver (and obtained through the diet by consumption of primarily meat, poultry, pork, and fish. Although, it’s also found in lesser quantities in dairy and other foods) as a source of energy for muscle and nerve cells. After creatine is metabolized in target tissue, the resulting creatinine enters the bloodstream (called serum creatinine) where it is taken to the kidneys for glomerular filtration and excretion through urine.8 Hence, creatinine concentrations in blood plasma allow doctors to evaluate the functional capacities of the kidneys. For this, the glomerular filtration rate (GFR) is utilized as a tool to determine the level of dysfunction. Normal GFR is considered to be 90 – 120 mL/min.9 A reading below 90 mL/min is enough to suspect a certain degree of renal affectation. However, at a persistently low level of 60 mL/min or less for 3 months, a stage III diagnosis of chronic kidney disease is made.10 Creatinine is normally almost entirely excreted.
How are BUN and creatinine related? Well, they are both nitrogen-based waste. Creatine is found in much lesser quantities in the blood because it’s almost entirely excreted via urine, whereas BUN is reabsorbed. This difference can be expressed in a BUN/creatinine ratio of 10:1 or 20:1 under normal circumstances.11 This ratio has clinical significance in that it paints a clearer picture as to what is happening in the coordination of kidneys with the metabolism. In simple terms, an elevated ratio, say 40:1, basically signals a problem of volume depletion due to low perfusion to the kidneys. A situation like this can be caused by malnutrition, congestive heart failure, a low-protein diet, severe liver disease, rhabdomyolysis, gastrointestinal bleeding, and dehydration. Because creatinine is supposed to be completely excreted via urine, it’s a more important marker for kidney disease, since urea levels can go up or down depending on many non-renal factors, such as diet. The BUN/creatinine ratio is an important renal indicator in a hemogram.
Cholesterol is a sterol, a lipid molecule that is involved in many crucial biochemical processes, and is found in cell membranes. It’s a vital precursor of several hormones (such as cholecalciferol); they provide fluidity and structure to cell membranes, interact with other membrane proteins, and are used by the liver for bile synthesis. The normal value in a hemogram is between 0 – 200 mg/dL of total cholesterol.12
There are 2 types of cholesterol depending on which protein is bound to it: high-density lipoprotein (HDL) and low-density lipoprotein (LDL). The former is colloquially called ‘good cholesterol’, and the latter is coined ‘bad cholesterol. The reason is that the function of LDL is to transport cholesterol to tissues in order to be used by the cells or for hormone synthesis. However, if LDL is too high, it causes lipidic deposits in vascular walls, whereas HDL helps remove them. If LDL deposits continue to accumulate, it can trigger a thromboatherosclerotic process, wherein the accumulated fat has the potential to grow large enough to obstruct, and thus minimize, vascular lumen diameter13; which causes decreased perfusion capabilities to the affected tissue. As this affectation progresses even further, the pressure created by turbulence (abnormal blood flow), along with increased mechanical friction and velocity from blood elements coming into contact with the thromboatherosclerotic plaque, can cause the clot (thrombus) to detach, travel through the bloodstream, and eventually clog an artery along the vessels caliber gradient. A clogged artery is deadly, as it can cause deep vein thrombosis, pulmonary embolism, and brain stroke among others. If tissue does not receive blood due to blockage, it becomes necrotic and dies.
Normal values are considered to be below 150 mg/dL14. Hypertriglyceridemia is a major risk factor for the development of atherosclerosis. We obtain them via metabolic synthesis from food we eat by esterification 3 fatty acid chains bonded to glycerol (glyceroneogenesis). As a lipid, the main function of triglycerides is to store extra calories for later use. We don’t obtain them directly through diet, we consume their precursors (such as glucose) which are used in the liver to produce triglycerides as a secondary source for energy in times of prolonged hunger.
High blood levels of this substance create an increased probability of many complications, such as hepatic steatosis and cardiovascular disease (atherosclerosis).
Besides a diet excessively high in fat, hypertriglyceridemia can be caused by hypothyroidism, diabetes, pancreatitis, cirrhosis, and nephrotic syndrome.
Low levels of triglycerides can indicate malabsorption syndrome, hyperthyroidism, and malnutrition.
Normal blood sugar value in a hemogram ranges between 70 – 100 mg/dL during fasting, whereas a reading of 100-125 mg/dL is considered prediabetes. Anything over 126 mg/dL is a red flag for diabetes, though other analyses need to be made for a definite conclusion.15
Glucose is a carbohydrate, the main source of energy for the human body. Adequate levels allow the proper functioning of digestion, respiration, muscle contraction, and corporal temperature regulation, among others.
There are 3 metabolic pathways for glucose:
- Storage in the liver in the form of glycogen.
- Oxidation via glycolysis to obtain pyruvate (for the Krebs cycle).
- Oxidation via pentose phosphate pathway to yield Ribose-5-phosphate (for nucleic acid synthesis).
High glucose in the blood is called hyperglycemia. The reasons for increased values in a hemogram during fasting include insulin deficiency or dysfunction, (100 – 126 mg/dL is considered glucose intolerance, while above 200 mg/dL is diabetes mellitus), corticoid medication, Cushing’s disease, stress, ‘Dawn’ phenomenon, and over-consuming carbs, especially the bad type.16
Low blood glucose is called hypoglycemia when the hemogram shows a reading below 70 mg/dL; and can be caused by a pancreatic tumor (insulinoma), alcoholism, cortisol deficiency, incorrect insulin injection technique, strenuous exercise, and not consuming enough carbohydrates or skipping meals.
As we can see, glucose is extremely important in several biological and physiological levels. Given the bombardment of anti-carb information out there, especially in fad diet marketing, it’s unsurprising that many people think all carbs are a bad thing, when what the scientific community is really saying is that with all of the sugary options available in virtually every supermarket aisle, it’s easy for the modern human to lose sight of what it means to have a balanced diet. The purpose of published scientific studies (besides informing the public) regarding carbohydrates is to gain perspective on where we stand on that balance so that we can evaluate it in relation to our everyday diet. Diabetes became a global epidemic precisely because the average person was or continues to be uninformed about carbohydrates while at the same time the market permeability and affordability of cheap refined sugars roared on (they are also carbs, which explains why carbs are associated with something bad). No wonder the prevalence and incidence of some diseases like diabetes grew exponentially. Looked at it simply, the trick is to eat high-quality carbs while keeping the low-quality at bay while never over-consuming ANY type, period. 17
Alkaline Phosphatase (ALP)
ALP is an enzyme abundantly found in hepatic, osseous, renal, and intestinal tissue. At a cellular level, it’s located on the membrane, where it interacts with biological molecules in the surroundings and other proteins along the membrane. Its fundamental functions are18:
- Synthesis of histamine proteins.
- Precipitation of calcium phosphate.
- Hydrolysis of phosphate esters in the liver and kidneys
- Phosphate absorption in the digestive system.
- Protein breakdown.
For adults, normal lab values are 44 – 147 IU/L.19 However, it varies based on gender, age, and other factors. Abnormalities in these readings should lead to suspicion of liver, gallbladder, or bone disease. Clinically, we analyze ALP to detect the 2 most common affectations, which are hepatic obstructive disease and metabolic bone disease. We can consider 2 variables that affect levels of ALP: an underlying disease and medication.
Low levels of ALP in a hemogram could be associated with hypophosphatasia, malnutrition, celiac disease, osteomalacia, inadequate mineral and vitamin consumption from the diet, and Paget’s disease.
- Adrian O. Hosten, Chapter 193 Bun and Creatinine (Clinical Methods: The History, Physical, and Laboratory Examinations, 3rdedition, 1990) https://www.ncbi.nlm.nih.gov/books/NBK305/
- Online Excretion and the Liver, (Royal Society of Chemistry, 2004) http://www.rsc.org/Education/Teachers/Resources/cfb/excretion.htm
- William C Rose, Eugene Dekker, Urea as a Source of Nitrogen for the Biosynthesis of Amino Acids (J. Biol Chem 1956) http://www.jbc.org/content/223/1/107.full.pdf
- David Weiner, William E. Mitch, Jeff M. Sands, Urea and Ammonia Metabolism (Clin J Am Soc Nephrol, August 2017) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527031/
- Lisa A. Foris, Khalid Bashir, Uremia (StatPearls November 2018) https://www.ncbi.nlm.nih.gov/books/NBK441859/
- A Brent Alper, Uremia Treatment and Management (Emedicine, January 2019) https://emedicine.medscape.com/article/245296-treatment
- Chad Haldeman, et al., Creatinine Blood (University Rochester Medical Center, Encyclopedia) https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=167&ContentID=creatinine_serum
- Lydia Williamson, David New, How the Use of Creatine Supplements can elevate serum creatinine in the absence of underlying kidney pathology, (BMJ case,2014) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170516/
- [Online] Kidney.Org https://www.kidney.org/kidneydisease/siemens_hcp_gfr
- Euan Sandiland Euan A Sandilands,Neeraj Dhaun, James W Dear, and David J , Webb, Measurement in Renal Function in Patients with Chronic Kidney Disease.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791974/
- Verena Gounden, Ishwarlal Jiaral, Renal Function Tests (StatPearls, 2018) https://www.ncbi.nlm.nih.gov/books/NBK507821/
- [Online] Marianne Frasier, et al., Lipid Panel with Total Cholesterol: HDL ratio. https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=167&ContentID=lipid_panel_hdl_ratio
- [Online] Medlineplus.Gov (US National Library of Medicine) https://medlineplus.gov/ldlthebadcholesterol.html
- [Online] MayoClinic Staff, Triglycerides: why do they matter? (September 2018) https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186
- [Online], MayoClinic Staff Diabetes, Diagnosis https://www.mayoclinic.org/diseases-conditions/diabetes/diagnosis-treatment/drc-20371451
- James Norman, MD, Diagnosing Diabetes (April 2016) https://www.endocrineweb.com/conditions/diabetes/diagnosing-diabetes
- Fortin A, et al. Practices, perceptions and expectations for carbohydrate counting in patients with type 1 diabetes – Results from an online survey (Diabetes Research and Clinical Practice) https://www.ncbi.nlm.nih.gov/pubmed/28273644
- Ujjawal Sharma, et al. Alkaline Phosphatase: An Overview (Indian Journal of Clinical Biochemistry, Nov. 2013) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062654/
- Laura J. Martin, et al., ALP Blood test (MD, MedlinePlus.Gov, May 2017 https://medlineplus.gov/ency/article/003470.htm