Dr. Catherina Pinnaro and her research team have just published a new report indicating benefits to reviewing diabetes device blood sugar data. The article is entitled “Diabetes Device Downloading: Benefits and Barriers Among Youth with Type 1 Diabetes”, and was just published as a peer reviewed research article in the Journal of Diabetes Science and Technology (pubmed Link; doi Link). Importantly, the data suggest that blood sugar levels improve when patients/families make insulin plan adjustments based on review of recent blood sugar patterns. Co-authors on the work from our division included Drs. Tansey, Tsalikian, and Norris. Also contributing as the lead author was future pediatric endocrinologist Dr. Benjamin Palmer.
Before 1922 type 1 diabetes was a rapidly fatal disease. That changed in the span of a few history-changing months. In the summer of 1921 four scientists at the University of Toronto began studying how to extract insulin from the pancreas and made quick progress. The first injection occurred on January 11, 1922, when an experimental insulin extract was administered to an adolescent who was dying of type 1 diabetes, saving his life. Soon thereafter commercial insulin production began and insulin use became widespread. However, there were many shortcomings of early insulin therapy, which was “regular” insulin extracted from cow and pig pancreases. These insulin preparations did not work in a uniform way from person-to-person. Extreme blood sugar swings were common and complications abounded. Thankfully, in the intervening century numerous improvements to insulin preparations and insulin delivery have been made. Dr. Pinnaro and Dr. Tansey from our division have just published an overview of these improvements in the Journal of Diabetes Mellitus. Their review is entitled “The Evolution of Insulin Administration in Type 1 Diabetes” (click on title for link to the article). Despite these improvements, insulin delivery for patients with type 1 diabetes remains imperfect. Importantly to this end, the article also discusses anticipated improvements that may help future generations of persons with type 1 diabetes. We are thankful for all those who worked to discover and improve insulin therapy, and look forward to future improvements! We thus thank all the diabetes research teams who are working tirelessly to improve diabetes care. This includes the Pediatric Diabetes research team here at the University of Iowa, whose dedication and expertise has helped advance diabetes care through carefully run studies. Finally, to those youth and families affected by type 1 diabetes, know that we look forward to every opportunity to work with you to optimize your insulin delivery and diabetes care. Advances in insulin therapy are happening rapidly. If your diabetes control is not what you think it should be, we would love for you to reach out to us to discuss options.
The American Thyroid Association (ATA; link) is arguably the leading organization worldwide dedicated to advancing care of persons with thyroid disorders through research, education, and promotion of clinical excellence. Dr. Liuska Pesce, of the pediatric endocrinologists in our division, has now been named to the ATA’s Board of Directors. As such, she will serve to help guide the ATA as they seek to improve thyroid care. Dr. Pesce has long-standing expertise in thyroid disorders and their treatment. She trained in part under the mentorship renowned thyroid-researcher Peter Kopp. Dr. Pesce joined the faculty at the University of Iowa Stead Family Department of Pediatrics in 2008. Here, she has established herself a leading expert in treatment of pediatric thyroid disorders including hypothyroidism, hyperthyroidism, thyroid hormone resistance, and thyroid cancers. We are enthused that she will share her expertise with the ATA.
Post by Andrew Norris, MD PhD Director, Pediatric Endocrinology & Diabetes University of Iowa Stead Family Children’s Hospital
“Don’t just look at the pH when interpreting a blood gas. If you only look at the pH, you will likely underestimate or even overlook metabolic acidosis.“
Metabolic acidosis is frequently encountered in clinical medicine. It is crucial that clinicians be able to recognize metabolic acidosis, characterize the specific type of acidosis, and assess its severity. This primer is focused on metabolic acidosis, and does not delve into other acid-base disturbances (i.e. metabolic alkalosis, respiratory acidosis and respiratory alkalosis).
Outline/topics Pearls Quick cookbook Important pitfalls What is metabolic acidosis? ◦ Background – soda & vinegar ◦ Metabolic acidosis – a simple definition ◦ Metabolic acidosis – an even simpler definition ◦ Symptoms of metabolic acidosis Diagnosis of metabolic acidosis ◦ Laboratory tests related to metabolic acidosis ◦ Blood gas interpretation in metabolic acidosis Causes of metabolic acidosis ◦ Major metabolic acidosis categories ◦ Some common causes of metabolic acidosis with elevated anion gap ◦ Some common causes of metabolic acidosis with normal anion gap ◦ Mixed acid-base disorders Footnotes
Pearls
A low serum bicarbonate usually indicates metabolic acidosis. For this reason, serum bicarbonate is a effective test for metabolic acidosis under most conditions.
Don’t just look at the pH when interpreting a blood gas. Metabolic acidosis is usually accompanied by a significant degree of respiratory compensation that brings the pH back towards normal. If you only look at the pH, you will likely underestimate or even overlook metabolic acidosis.
Determine the underlying cause. Metabolic acidosis has numerous possible causes, many of which are medical emergencies requiring timely diagnosis and institution of specific therapy.
An anion gap can help determine the type of metabolic acidosis present.
Quick cookbook
Obtain laboratory test(s): blood gas and/or serum bicarbonate
Interpret test results
Serum bicarbonate: low value indicates metabolic acidosis
Blood gas: must be fully interpreted, including
pH: low value indicates acidosis; high value indicates alkalosis
calculated bicarbonate: low value indicates metabolic acidosis
base excess: negative values below the reference range indicate metabolic acidosis
Obtain anion gap if metabolic acidosis is present.
If elevated: possible etiologies include diabetic ketoacidosis, lactic acidosis, specific inborn errors of metabolism, severe renal failure, or poisoning.
If normal: possible etiologies include GI or renal bicarbonate losses, compensation for chronic respiratory alkalosis, or hyperchloremic acidosis during resolution of DKA.
Determine the underlying cause: using additional diagnostic tests and clinical reasoning
Treat underlying cause.
Important pitfalls
Failure to fully interpret a blood gas. Often, acute metabolic acidosis is accompanied by a substantial degree of respiratory compensation (i.e. Kussmaul breathing).
Failure to determine the underlying cause. It is critical to correctly diagnosis the underlying etiology that has caused the metabolic acidosis. Some of the common causes of metabolic acidosis are medical emergencies requiring urgent specific treatments.
What is metabolic acidosis?
Background – soda & vinegar
Vinegar + soda: vinegar and sodium bicarbonate were combined, along with water, dish detergent, and trypan blue. Equivalently, ketoacids react with bicarbonate in the blood stream, causing metabolic acidosis.
The body uses a bicarbonate buffering system for maintenance of acid-base status. This is a system you may have learned as a child when playing experimenting with baking soda and vinegar. The chemistry is simple, and can be written as follows:
In health, by controlling the amount of bicarbonate (HCO3–, a base) and carbon dioxide (CO2) in the blood, the body is able to maintain pH near 7.40.
The same system is at play with baking soda and vinegar. Baking soda contains HCO3–. Vinegar is an acid, and supplies H+. When the two are combined, water and carbon dioxide gas are formed. The carbon dioxide bubbles are the fun part. The more important part, at least from a physiological view, is what happens to the pH. After equilibrium is reached, if vinegar is in excess, the pH will be acidic. Conversely, if bicarbonate is in excess, then the pH will be basic.
Metabolic acidosis – a simple definition
Metabolic acidosis occurs when the amount of acid (H+) in the blood is too high or when the amount of bicarbonate (HCO3–) is too low. (b)
Metabolic acidosis – an even simpler definition
Metabolic acidosis is present when the amount of bicarbonate (HCO3–) in the blood is too low.
Notice that this definition omits the “excess acid (H+)” part of the definition. To understand why this part of the definition can be omitted, we can turn back to the vinegar / soda experiment. When vinegar (a source of H+) is added to bicarbonate, the two react to form CO2 + H2O. Bicarbonate is depleted as this reaction proceeds. The same happens in the body when excess H+ is present – bicarbonate is depleted (c) and the serum HCO3– drops (d) .
Symptoms of metabolic acidosis
Acute metabolic acidosis is often accompanied by Kussmaul respirations, as the body attempts to reduce pCO2 in order to normalize pH. This respiratory pattern becomes more pronounced as the acidosis becomes more severe. Other symptoms are less specific but can include fatigue, weakness, tachycardia, abdominal pain and vomiting, headache, and confusion. At its severe extreme, metabolic acidosis induces coma and circulatory collapse.
Diagnosis of metabolic acidosis
Laboratory tests related to metabolic acidosis
Blood gas: A blood gas is an effective test to assess for and quantify metabolic acidosis. A blood gas measurement also informs about the respiratory component of pH (i.e. carbon dioxide). A blood gas is the primary means to distinguish whether acidosis is due to primary metabolic versus respiratory versus mixed issues. Importantly, the clinician must fully interpret the blood gas, beyond simply looking at the pH, pCO2 and pO2.
Serum bicarbonate(e): Measurement of the serum bicarbonate is also an effect means to assess for and quantify metabolic acidosis. As discussed above, a low bicarbonate indicates the presence of metabolic acidosis. There are a few circumstances when a serum bicarbonate lower than the reference range can be normal for a person, namely to compensate for respiratory alkalosis; this is detailed below.
Anion gap: Can help determine the nature of metabolic acidosis.
Chloride: Can help determine the nature of metabolic acidosis.
Units: A brief note about scientific units. In most U.S. hospitals, bicarbonate, anion gap, and chloride are all reported in mmol/L. Likewise, some of the major acidosis inducing anions, lactate and beta-hydroxybutyrate are typically reported in mmol/L. This makes internal comparison of these values simple. For example, 10 mmol/L beta-hydroxybutyrate in the serum would be expected to add 10 mmol/L to the anion gap and also to lower the serum bicarbonate by roughly the same amount.
Blood gas interpretation in metabolic acidosis
When checking for metabolic acidosis using a blood gas, it is critical to look at more than the pH. Looking at only the pH can cause one to underestimate the severity of the metabolic acidosis or even miss the presence of metabolic acidosis altogether.
To assess for metabolic acidosis, examine the following two parameters
HCO3– : calculated bicarbonate. If this is abnormally low, then metabolic acidosis is present.
“Base excess“: This is normally near zero. If it is abnormally below zero, then metabolic acidosis is present.
Complete interpretation of blood gas is beyond the scope of this primer. See footnote (f) for some free resources to learn more.
Causes of metabolic acidosis
Major metabolic acidosis categories
Elevated anion gap: A very important discriminant of the nature of metabolic acidosis is the presence or absence of an anion gap. When the anion gap is elevated, this indicates the presence of an acid. To use our vinegar–soda analogy, adding vinegar to blood would increase the anion gap (acetate being the unmeasured anion) and lower serum bicarbonate. Common causes of elevated anion gap metabolic acidosis include diabetic ketoacidosis, lactic acidosis, poisonings, some inborn errors of metabolism, and renal failure.
Normal anion gap: Typically, normal anion gap acidosis will be accompanied by relative hyperchloremia, and thus is often called “hyperchloremic acidosis”. Common causes include excessive bicarbonate losses via the renal or GI system, or chloride administration during resolving anion-gap acidosis.
Some common causes of metabolic acidosis with elevated anion gap
Diabetic ketoacidosis (DKA): In this condition, runaway production of ketoacids plays the equivalent role of vinegar, inducing a metabolic acidosis. Typically beta-hydroxybutyrate is the major ketoacid but acetoacetate production is also excessive. Acetone levels are also elevated, but acetone is not an acid itself. Tissue perfusion can be compromised, inducing lactic acidosis as well, further exacerbating the metabolic acidosis. Laboratory findings include: (i) diminished serum bicarbonate, (ii) acidic pH, (iii) elevated anion gap, (iv) elevated serum beta-hydroxybutyrate and acetone. Insulin is used to halt ketoacid production. In severe DKA, the serum bicarbonate can approach zero and the pH can dip below 7.0. As ketoacidosis resolves, the bicarbonate climbs as does the pH while the anion gap normalizes. Often, the ketoacidosis resolves before the renal system can fully replace chloride with bicarbonate, leading to a transient hyperchloremic acidosis, though the pH is usually much improved by this stage.
Lactic acidosis: This can be caused by hypoxia, systemic inflammatory response syndrome, tissue injury, and more rarely specific inborn errors of metabolism.
Poisonings / intoxications: Causative agents include methanol, ethylene glycol, salicylates. Of note, many of these will cause an osmolar gap.
Uremia / severe end-stage renal failure: Due to retention of sulfate, phosphate and various organic acids.
Some common causes of metabolic acidosis with normal anion gap
GI loss of bicarbonate. Apart from the stomach, the GI tract is a bicarbonate secreting organ. Excessive loss of GI fluids, such as with diarrhea or pancreatic/biliary drains causes a metabolic acidosis with normal anion gap.
Renal loss of bicarbonate: In health, the kidney reabsorbs copious bicarbonate. Renal tubule dysfunction can interfere with this reabsorption and cause bicarbonate loss and metabolic acidosis with a normal anion gap.
Hyperchloremic acidosis during resolution of anion-gap acidosis. This is discussed above under DKA.
Mixed acid-base disorders
Acid-base disorders typically will induce a degree of compensation. Primary metabolic acid-base disturbances induce respiratory compensation, which occurs very rapidly. Primary respiratory acid-base disturbances induce metabolic compensation, though this occurs more slowly – over hours-to-days. Additionally, if the patient has more than one pathological condition at play, there may be additive respiratory plus metabolic disturbances. Ascertainment of these mixed acid-base disturbances requires a blood gas measurement. See footnote (f) for some free resources to learn more about these mixed disorders and their blood gas correlates. A simple summary follows, divided into two sections depending on whether the patient’s blood pH is acidic or alkaline.
Acidic pH
↓CO3– + ↓pCO2 = metabolic acidosis with respiratory compensation
Note: this is the most common scenario with metabolic acidosis.
↓CO3– + ↓pCO2 = respiratory alkalosis with metabolic compensation
Note: this is an occasion when a lower CO3– represents a physiological response. Illustratively, this scenario occurs at high altitudes. The thinner air at high elevations requires greater minute ventilation to maintain oxygenation. The increased ventilation induces a respiratory alkalosis, which then over time leads to compensatory decreases in serum bicarbonate mediated by renal losses. See PMID:27120676 .
These climbers are over 4,000 meters above sea level and thus expected to have a mixed acid-base disturbance including a physiological base deficit of roughly 4 mEq/L.
Footnotes
(a) Technically speaking, the reaction includes H2CO3 as an intermediate. In written form,: HCO3– + H+ ⇋ H2CO3 ⇋ H2O + CO2 . However, H2CO3 is unstable in aqueous systems and only exists very briefly and thus in effect does not play into the overall equilibrium.
(b) Conversely, respiratory acidosis occurs when blood carbon dioxide (pCO2) is too high.
(c) When H+ is added to bicarbonate, CO2 is produced. This appears as bubbles in the soda & vinegar experiment. In the body, much more minute quantities are involved and bubbles are not formed but rather the excess CO2 is dissolved in the blood and rapidly circulates to the lungs where it is exhaled.
(d) Likewise, if bicarbonate drops, there will be a shift of CO2 + H2O to produce H+ and CO3–, thus producing a net effect to raise H+ thus lowering the pH.
(e) This laboratory test is alternatively called “tCO2 or total CO2 (carbon dioxide)” or simply “serum CO2”. In fact, typically these tests measure the amount of bicarbonate plus carbon dioxide in the liquid sample. The molar amount of carbon dioxide in most clinical samples is far less than the amount of bicarbonate. Hence despite these alternative names, the reported value represents primarily serum bicarbonate. Factitiously low serum bicarbonate can occur. Importantly, phlebotomy-related issues can impact acid-base analytes. For example, samples smaller than intended for their collection tube can lose excess pCO2, thus altering the buffering equilibrium in favor of converting bicarbonate to carbon dioxide which is then lost from the sample. This is especially true in underfilled vacuum containers.
Today the Iowa Institute of Public Health Research and Policy help its 3rd annual Healthy Lifestars Conference. This year’s topic was “Improving Health Outcomes Through Preventing Childhood Obesity”. Our division’s Dr. Kanner spoke at the conference on her area of expertise. Her talk was entitled “The Impact of Adolescent Polycystic Ovary Syndrome on Obesity and the Accompanying Lifestyle and Medicine Management Requirements“. This is one of her areas of clinical expertise. She heads the University of Iowa Stead Family Children’s Hospital pediatric polycystic ovary syndrome clinic.
The University of Iowa Hospitals and Clinics has been designated a Center of Excellence for Care of patients with Pheochromocytoma and Paraganglioma. There are only 6 such other centers across the United States. The designation comes from the Pheo Para Alliance, which is a leader in advocacy regarding patients with pheochromocytoma and paraganglioma. Pheochromocytomas and paragangliomas are neuroendocrine tumors that secrete adrenaline-like hormones. The tumors can usually be successfully treated, but require careful expert care to avoid severe complications. Our center of excellence represents a multidisciplinary collaboration between pediatric endocrinology, adult endocrinology, oncologists, surgical specialists, and clinical genetics. A special thanks to Dr. Liuska Pesce, who is the pediatric endocrinologist for the Center. To learn more, visit the centers webportal.
We are proud to note that the University of Iowa Stead Family Children’s Hospital has maintained its recognition by the National Pancreas Foundation as a Center of Excellence for treatment of youth with pancreatitis. Pancreatitis is uncommon in children, but requires expert multidisciplinary care including specialists from gastroenterology, endocrinology, radiology, and surgery. Diabetes is a common complication of recurrent pancreatitis. Pancreatitis-related diabetes is not the same as type 1 or type 2 diabetes, and can have specific treatment considerations. As such, it requires expertise from an experienced pediatric endocrinologist, such as Dr. Katie Larson Ode, who is the lead pediatric endocrinologist who works with the pancreatitis clinic here. You can read more about the designation at the original press release here.
Congratulations to Dr. Katie Larson Ode, who was just named the recipient of a research grant award. The award comes from the joint Minnesota-Iowa Diabetes Research Center (MIDRC) as part of an initiative to foster collaborative diabetes research between the two institutions. For the research project, Dr. Larson Ode has teamed up with Univ of Minnesota physician Dr. Melena Bellin, whom is also a pediatric endocrinologist. A portion of children who develop chronic or recurrent acute pancreatitis will develop diabetes. However, the reasons for this are poorly understood. To better understand why, and hopefully delineate preventative strategies, Drs. Larson Ode and Bellin will enroll children with pancreatitis into a study in which glucose monitors and meal tests will be used to determine how well their pancreases are functioning to produce insulin and control blood sugar.
We were graced today by a clinical grand rounds talk from Philippe Backeljauw, MD. Dr. Backeljauw is Professor at the University of Cincinnati Department of Pediatrics. He is also Director of their Pediatric Endocrine Fellowship Program and Director of the Cincinnati Center for Pediatric and Adult Turner Syndrome Care. He spoke at our Pediatric Grand Rounds. Dr. Backeljauw is an internationally recognized expert in the clinical care of patients with growth disorders and patients with Turner syndrome. He received his MD from the University of Ghent in Belgium, completed pediatric residency at Cleveland Clinic, and pediatric endocrinology fellowship at the University of North Carolina. He has published over 100 peer-reviewed manuscripts. Recently, he was instrumental in devising clinical practice guidelines related to Turner Syndrome via the International Turner Syndrome Consensus Group. Dr. Backeljauw spoke today on the “Clinical Management of Turner Syndrome”.
Recently, Dr. Norris co-authored a new chapter entitled “Glucose Metabolism in the Fetus and Newborn, and Methods for Its Investigation“. The chapter is part of the newly published Fetal and Neonatal Physiology textbook, 6th edition, edited by Polin, Abman, Rowitch & Benitz (Hardcover ISBN: 9780323712842). This is one of the leading standard textbooks for perinatal and neonatal physicians. Dr. Norris co-authored the chapter with Dr. Sarah A. Wernimont, who is an maternal-fetal medicine faculty physician at the University of Minnesota. Both Dr. Wernimont and Dr. Norris have directed research aimed at better understanding glucose metabolism in the maternal-fetal system. The textbook is available from publisher Elsevier and also at commercial book outlets.
