Pernicious Anemia


Article Author:
Nicole Rodriguez


Article Editor:
Karen Shackelford


Editors In Chief:
William Gossman


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
4/10/2019 10:44:37 AM

Introduction

Pernicious anemia (PA) is megaloblastic anemia which results from a deficiency in cobalamin (vitamin B12) due to a deficit of intrinsic factor (IF). Intrinsic factor is a glycoprotein which binds cobalamin and therefore enables its absorption at the terminal ileum.

Pernicious anemia is often described as an autoimmune disorder due to the findings of gastric autoantibodies directed against both IF and parietal cells. Pernicious anemia also correlates with other autoimmune disease and as well as a genetic disease.[1]

The clinical presentation of pernicious anemia is multifarious and insidious in onset. Symptoms may include fatigue, pallor, paresthesia, incontinence, psychosis and generalized weakness. The diagnosis is problematic secondary to the restricted availability of diagnostic tools. Treatment aims at repletion of therapeutic doses of vitamin B12 either through intramuscular injections or orally. When the disease remains undiagnosed and untreated for an extended period, it may lead to neurological complications and even fatal anemia.

The present article exposes the epidemiology, pathogenesis, clinical presentation, evaluation, and treatment of pernicious anemia. 

Etiology

Research has identified two etiologies for pernicious anemia:

1. Autoimmune: 

Autoimmune gastritis characterized by the destruction of gastric parietal cells and the resulting lack of the glycoprotein intrinsic factor which is secreted by these cells. The antibodies identified with autoimmunity are: 

Intrinsic factor antibodies (IFA) and parietal cell antibodies (PCA)

Parietal cell antibodies: They work against the parietal cell proton pump ATPase. The primary targets of parietal cell antibodies are the proton pump subunits: alpha and beta. Parietal cell antibodies are determined to be immunoglobulins from the following isotypes: M, G, and A, which operate against both subunits.[2] 

Intrinsic factor antibodies: These are immunoglobulin G isotype, and they can be either type 1 or type 2 antibodies. Type 1 conducts against the cobalamin binding site. Type 2 acts against the ileal mucosa receptor.[3]

Other autoimmune diseases: 

Pernicious anemia can be associated with autoimmune diseases, such as type 1 diabetes (3% to 4%), vitiligo (2% to 8%), and autoimmune thyroid disease (3% to 32%). This association has led to studies exposing that HLA alleles may be related to autoimmune gastritis. HLA-DRB1/03 and HLA-DRB1/04 alleles may predispose to autoimmune gastritis.[4][1]

2. Genetics: 

Researchers have also identified congenital and juvenile forms of pernicious anemia which are thought to follow an autosomal recessive inheritance pattern.

Epidemiology

Some studies state that the prevalence of pernicious anemia is 0.1% in the general population which increases to 1.9% in patients aged older than 60 years.[5]

All age groups are affected, yet it gets most frequently associated as a disease of adults greater than 60 years of age with the median age being 70 to 80 years. 

Estimates of prevalence in the U.S.A. are 151 per 100000. 

The prevalence in persons of European and African ancestry is more common in older adults (4.0% and 4.3% prevalence, respectively) than in those of Asian descent.[6]

Pathophysiology

In PA there are two types of autoantibodies identified: intrinsic factor antibodies (IFA) and parietal cell antibodies (PCA)

1. Parietal cell antibodies conduct their activity against the parietal cell proton pump ATPase. 

Autoimmunity begins by the activation of gastric dendritic cells which in turn trigger CD4+ T cell lymphocytes in perigastric lymph nodes. These triggered CD4+ T cells identify the proton pump ATPase, which leads to their immune destruction.[7]

The mechanism by which the dendritic cells activate is not known. Some research studies suggest H. pylori infection as a trigger. The studies propose molecular mimicry and immune cross-reactivity between the proton pump ATPase and the H. pylori organisms.[8][9]

2. Intrinsic factor antibodies are immunoglobulin G isotype, and they can be either type 1 or type 2 antibodies.

Type 1 operates against the cobalamin binding site. Type 2 directs its activity against the ileal mucosa receptor.[3]

B12 and intrinsic factor bind to receptors on the ileum, which allows for absorption. 

Vitamin B12, once absorbed, is a cofactor for the enzyme methionine synthase, which takes part in the conversion of homocysteine to methionine. If this process is unable to occur due to pernicious anemia, homocysteine levels accumulate, and pyrimidine bases cannot form, which interferes with DNA synthesis and causes megaloblastic anemia.  

Vitamin B12 is also a cofactor for the enzyme methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA. In patients with pernicious anemia methylmalonic acid (MMA) levels accumulate. Elevated levels of MMA and homocysteine, contribute to myelin damage, which causes neurologic deficits, such as neuropathy and ataxia.[10]

History and Physical

The clinical presentation of pernicious anemia is often insidious, and symptoms may vary during its course. Patients often lack awareness of their symptoms, or they may have become used to them.

A clinician should perform a complete history, including a detailed past medical history and family history which important focus on autoimmune disease.

The clinician should conduct a complete physical exam with emphasis on hematological, gastrointestinal, and neurological findings. 

  • Hematological manifestations: pallor, fatigue, shortness of breath, dizziness, tachycardia, lightheadedness, and decreased cognitive and physical function
  • Gastrointestinal manifestations: abdominal bloating, loss of appetite, weight loss, and diarrhea 
  • Neurological manifestations: Peripheral neuropathy, paresthesia, weakness, ataxia, forgetfulness, and psychosis

Pernicious anemia, if left untreated, may be fatal. 

Evaluation

Initial lab tests include:

Complete blood count (CBC), serum B12 levels, and a peripheral smear. 

The CBC should demonstrate anemia, as shown by a decrease in hemoglobin and hematocrit (hemoglobin concentration less than 13 g/dL for men and less than 12 g/dL for women). The mean corpuscular volume (MCV) would be greater than or equal to 100 fL, an expected finding in macrocytic anemia. The peripheral blood smear may demonstrate hyper-segmented neutrophils (neutrophils with five lobes or greater). B12 levels of under 200 pg/mL are considered deficient.

After initial lab tests confirm B12 deficiency, the diagnosis of pernicious anemia will depend on further testing: the presence of atrophic body gastritis (ABG) and intrinsic factor deficiency.[1]

Diagnostic criteria for ABG require a histological sampling of gastric body mucosa. Findings associated with PA are the presence of corpus-restricted atrophy with a spared antrum, as well as the presence of hyperplasia of ECL cells. 

Serological markers can also aid in identifying ABG for example increased levels of fasting gastrin and decreased levels of pepsinogen I suggest the presence of mucosal damage.

Intrinsic factor deficiency can be evaluated by the Shilling test, which is now being replaced by other diagnostic strategies such as the detection of intrinsic factor antibodies. Antibodies to intrinsic factor can be of two types: The blocking type, against the B12 binding site present in 70% of patients and antibodies to parietal cells present in 90% of patients, but it is less specific.

Alternative and new approaches to the diagnosis of PA are under evaluation. One of these is the Cobasorb test, which has its basis in the measurement of the change in holoTC following oral ingestion of non-radiolabeled cobalamin. Another approach has been described using accelerator mass spectrometry to quantify 14C in the blood following an orally administered dose of [14C]-cyanocobalamin.[11]

Treatment / Management

Treatment:

Patients generally receive an intramuscular injection of 1000 mcg B12 every day or every other day during the first week of treatment. The next month, they receive injections every week, subsequently followed by monthly injections. 

The alternative to intramuscular injection B12 is high-dose oral B12. A 1000 to 2000 mcg/day has been demonstrated to be effective, although recommendations are to always use the parenteral route in severe neurological manifestations.

Approved sublingual and intranasal formulations of B12 are also available.[1][12]

Monitoring: 

The earliest sign of treatment response is an increase in reticulocyte count, usually within three days of treatment. Following changes in the decrease of biochemical markers such as MMA and plasma homocysteine levels have been observed in the first five days of treatment. 

Sustained normalization of serum cobalamin usually occurs following two weeks of therapy.[13]

The macrocytosis correction takes place during the first month of treatment. 

A clinical interview should be considered every year, to attest the commencement of new symptoms.

These may include epigastric pain, dysphagia, iron-deficiency, and/or others that can require gastroscopic investigation.

The key management principle is the importance of routine follow-up. 

Differential Diagnosis

  • Increased erythropoiesis: response to hemorrhage, hemolytic anemia
  • Hypoplastic anemia
  • Myelodysplastic syndrome
  • Ileal disease or resection
  • Gastrectomy
  • Liver disease 
  • Chronic obstructive pulmonary disease
  • Proton pump inhibitor therapy
  • Fish tapeworm
  • Pancreatic insufficiency
  • Corpus-predominant H. pylori gastritis
  • Drugs (phenobarbital, azathioprine, methotrexate, 6-mercaptopurine, 5-fluorouracil, acyclovir)
  • Vegetarianism

Prognosis

Prognosis is variable, and most pernicious anemia patients have a subtle progression that can take 20 to 30 years or even more to become clinically significant.

Even with a relatively benign prognosis, pernicious anemia can have fatal consequences if left undiagnosed. These consequences can be secondary to severe anemia and its complications, neurological compromise, and susceptibility to all types of gastric tumors.

Complications

The complications associated with pernicious anemia are extensive, varying from mild symptoms such as fatigue to life-threatening pancytopenias.

Anemia is the most frequent clinical sign. Other hematological manifestations such as neutropenia, thrombocytopenia, pancytopenia due to ineffective erythropoiesis, and pseudothrombotic microangiopathy may be present. Thromboembolic events are also a complication. 

Glossitis (inflammation of the tongue) may occur secondary to papillary atrophy resulting in a bald tongue and a burning sensation upon contact with different types of food. 

Neurological signs are usually present due to subacute combined degeneration of the spinal cord. Manifestations are predominantly in the lower limbs. The damage to myelin is responsible for ataxia, areflexia, and paresthesias with positive Romberg signs.

The development of gastric carcinoid tumors is also a possible complication.[12]

Deterrence and Patient Education

Pernicious anemia is an often silent and insidious autoimmune disease. Patients may become acclimated to their complaints. Health care providers should increase their awareness of this disorder to provide the best patient outcomes.

Pearls and Other Issues

 

 

Enhancing Healthcare Team Outcomes

Pernicious anemia is often an insidious and under-diagnosed autoimmune disorder, which can lead to fatal complications.

The most appropriate way to supervise this disorder is through interprofessional and interdisciplinary teams that include a primary care physician, internist, gastroenterologist, neurologists, oncologists, pharmacists, and nurses. [Level V]

The healthcare team should strive to increase awareness of the disease and therefore promptly test for it. The nurse can intervene in a primary screening during triage by asking for signs and symptoms suggestive of underlying anemia, neurological or gastroenteric manifestations. 

The most at risk population include people over 60 years of age. These older individuals should receive prospective screening for possible vitamin B12 deficiency.

Once treated, the patients should be supervised routinely by their physician.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Pernicious Anemia - Questions

Take a quiz of the questions on this article.

Take Quiz
Which type of anemia is characterized by hypersegmented neutrophils and an elevated mean cell volume and mean cell hemoglobin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is used in the treatment of pernicious anemia?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A female is diagnosed with pernicious anemia. Which of the following statements about pernicious anemia is true?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What produces intrinsic factor?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Cyanocobalamin is used to treat which of the following conditions?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient is being worked up for anemia and undergoes the Schilling test. What condition is test used to diagnose?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
In a patient suspected of having an abnormal first Schilling test and a normal second phase of the test, what would one suspect?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a common cause of vitamin B12 deficiency in patients over 60 years of age?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 60-year-old male is brought in by his wife with progressively worsening memory loss, paresthesias, ataxia, and impotence. Physical exam reveals upper motor neuron signs of both upper and lower extremities. To which of the following does the nutrient he has a deficiency binds?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 70-year-old female presents with a 1-year history of progressively worsening leg cramping with associated pins and needles sensation in her feet. She has noticed an imbalance in her gait as well. She has attributed urinary incontinence to “getting old.” Exam shows spastic paresis, decreased position sense, and decreased vibration sense. The deep tendon reflexes are absent at the knees. CBC shows macrocytosis and hypersegmented neutrophils. What is the most probable nutritional deficiency?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most common etiology of vitamin B12 deficiency in patients over 65 years?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 73-year-old male complains of severe fatigue for several months. Exam reveals pallor, positive Romberg test and decreased sensation in both lower extremities. CBC shows macrocytic anemia with hypersegmentation of neutrophils. What is the likely cause of this patient's neurological findings?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following conditions is an inflammatory response caused by antibodies reacting with parietal cells of gastric mucosa, resulting in atrophic gastritis and depressed acid secretion?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which autoimmune disorder is characterized by autoantibodies against intrinsic factor?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following statements made by a patient with pernicious anemia demonstrates an understanding of the disease?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
An 81-year-old female complains of fatigue, anorexia, and clumsiness. Exam shows a smooth tongue and loss of vibratory and position sense in the lower extremities. Laboratory studies reveal a hemoglobin 8.5 g/dL, hematocrit 25.1%, and MCV 120 fL. Microscopic examination of peripheral blood smear may show which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is one of the causes of pernicious anemia?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 65-year-old female presents with a 2-month history of muscle weakness, sore tongue, and tingling of forearms and hands bilaterally. Her bloodwork reveals low hemoglobin, a normal mean corpuscular hemoglobin concentration, and a markedly increased lactate dehydrogenase. What other finding is expected if the patient is diagnosed with pernicious anemia?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What type of anemia is caused by maturation failure of red blood cells?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following vitamins is used in the treatment of pernicious anemia?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
If a patient has pernicious anemia, they will require lifelong monthly injections of or high dose oral therapy of which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Pernicious Anemia - References

References

Lahner E,Annibale B, Pernicious anemia: new insights from a gastroenterological point of view. World journal of gastroenterology. 2009 Nov 7;     [PubMed]
Callaghan JM,Khan MA,Alderuccio F,van Driel IR,Gleeson PA,Toh BH, Alpha and beta subunits of the gastric H /K( )-ATPase are concordantly targeted by parietal cell autoantibodies associated with autoimmune gastritis. Autoimmunity. 1993;     [PubMed]
Conn DA, Detection of type I and type II antibodies to intrinsic factor. Medical laboratory sciences. 1986 Apr;     [PubMed]
Fernando MM,Stevens CR,Walsh EC,De Jager PL,Goyette P,Plenge RM,Vyse TJ,Rioux JD, Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS genetics. 2008 Apr 25;     [PubMed]
Yousaf F,Spinowitz B,Charytan C,Galler M, Pernicious Anemia Associated Cobalamin Deficiency and Thrombotic Microangiopathy: Case Report and Review of the Literature. Case reports in medicine. 2017;     [PubMed]
Stabler SP, Vitamin B12 deficiency. The New England journal of medicine. 2013 May 23;     [PubMed]
Toh BH,Sentry JW,Alderuccio F, The causative H /K ATPase antigen in the pathogenesis of autoimmune gastritis. Immunology today. 2000 Jul;     [PubMed]
Chmiela M,Gonciarz W, Molecular mimicry in {i}Helicobacter pylori{/i} infections. World journal of gastroenterology. 2017 Jun 14;     [PubMed]
Uibo R,Vorobjova T,Metsk�la K,Kisand K,Wadstr�m T,Kivik T, Association of Helicobacter pylori and gastric autoimmunity: a population-based study. FEMS immunology and medical microbiology. 1995 Mar;     [PubMed]
Ankar A,Kumar A, Vitamin B12 Deficiency (Cobalamin) 2018 Jan;     [PubMed]
Green R, Vitamin B{sub}12{/sub} deficiency from the perspective of a practicing hematologist. Blood. 2017 May 11;     [PubMed]
Andres E,Serraj K, Optimal management of pernicious anemia. Journal of blood medicine. 2012;     [PubMed]
Nazarenko GI,Kolenkin SM,Lugovskaia SA,Mikolauskas VP, [Significance of parameters of automated reticulocyte analysis in diagnosis and evaluation of treatment outcome in B12-deficient anemia]. Klinicheskaia laboratornaia diagnostika. 2004 May;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Adult Ambulatory-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Adult Ambulatory-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Adult Ambulatory-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Adult Ambulatory-Medical Student. When it is time for the Adult Ambulatory-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Adult Ambulatory-Medical Student.