Diseases » Proximal Renal Tubular Acidosis » Diagnosis

Diagnosis of Proximal Renal Tubular Acidosis

Proximal Renal Tubular Acidosis Diagnosis: Book Excerpts

• Ask the following questions - ANEMIA
• Ask the Following Questions - FATIGUE
• Ask the following questions - ACIDOSIS (DECREASED PH)
• Differential Diagnosis - Anemia
• Differential Diagnosis - Fatigue
• Differential Diagnosis - Anemia
• Differential Diagnosis - Fatigue
• Differential Diagnosis - Congenital Penile Anomalies
• Approach to the Diagnosis - ANEMIA
• Approach to the Diagnosis - WEAKNESS AND FATIGUE, GENERALIZED
• Approach to the Diagnosis - ACIDOSIS (DECREASED PH)
• History and physical examination - Fatigue
• History and physical examination - Tunnel vision [Gun barrel vision, tubular vision]
• Diagnosis - Renal tubular acidosis
• Diagnosis - Aplastic anemias
• Diagnosis - Folic acid deficiency anemia
• Diagnosis - Iron deficiency anemia
• Diagnosis - Pernicious anemia
• Diagnosis - Sickle cell anemia
• Diagnosis - Sideroblastic anemias
• Diagnosis - Chronic fatigue syndrome
• History and physical examination - Fatigue
• History and physical examination - Tunnel vision [Gun barrel vision, tubular vision]
• History - Fatigue
• Differential Overview - Anemia
• Differential Overview - Fatigue
• Diagnosis - Renal tubular acidosis
• Diagnosis - Aplastic and hypoplastic anemias
• Diagnosis - Chronic fatigue and immune dysfunction syndrome
• Diagnosis - Folic acid deficiency anemia
• Diagnosis - Iron deficiency anemia
• Diagnosis - Pernicious anemia
• Diagnosis - Sickle cell anemia
• Diagnosis - Sideroblastic anemias
• History - Fatigue
• Clinical Features and Diagnosis - Fatigue
• Clinical Features and Diagnosis - Pallor (Anemia)
• History and physical examination - Fatigue
• History and physical examination - Tunnel vision [Gun barrel vision, tubular vision]
• Approach to the Diagnosis - ANEMIA
• Approach to the Diagnosis - WEAKNESS AND FATIGUE, GENERALIZED
• Approach to the Diagnosis - ACIDOSIS (DECREASED pH)

Diagnostic Tests for Proximal Renal Tubular Acidosis: Online Medical Books

16 MEDICAL BOOKS ONLINE! Review excerpts from medical books online, free, without registration, for more information about diagnostis of Proximal Renal Tubular Acidosis.

ANEMIA: Ask the following questions:
(Algorithmic Diagnosis of Symptoms and Signs)

1. Is there a history of chronic blood loss? A history of peptic ulcer, ulcerative colitis, or other causes of chronic GI bleeding would indicate the anemia is most likely due to iron deficiency. Likewise, chronic hypermenorrhea or metrorrhagia in women of child-bearing age may lead to iron deficiency anemia.
2. Are there neurologic signs? Paresthesias, loss of vibratory sense, ataxia, and mild dementia should lead one to suspect pernicious anemia.
3. Is there jaundice? Clinical jaundice should arouse the suspicion of a hemolytic anemia, but mild clinical jaundice may be seen in pernicious anemia also. Chronic liver disease, such as alcoholic cirrhosis, is often associated with folate deficiency or sideroblastic anemia.
4. What is the white count? A decreased white count should alert one to the possibility of aplastic anemia, myelofibrosis, or infiltrative diseases of the bone marrow, such as carcinomatosis, Gaucher's disease, or lymphoma. It may also be related to pernicious anemia. An increased white count would suggest leukemia, chronic infections, anemia, or bacteremia.

DIAGNOSTIC WORKUP

The most important thing to do initially is to examine a blood smear for red cell morphology. If the anemia is microcytic, one would consider iron deficiency or chronic blood loss. If it is microcytic, consideration should be given to pernicious anemia or folate deficiency. Further workup should include a chemistry panel, stool for occult blood, liver function tests, reticulocyte count, serum iron and iron-binding capacity, serum B ₁₂ and folic acid, serum haptoglobin, and platelet count. If these studies are inconclusive, a hematologist should be consulted. A hematologist will perform a bone marrow examination for a more definitive diagnosis. Perhaps a liver-spleen scan, CT scan of the abdomen, or therapeutic trial of iron, B ₁₂ , or folic acid is indicated.

 

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Source: Algorithmic Diagnosis of Symptoms and Signs, 2003

FATIGUE: Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)

1. Is there weight loss? If there is weight loss, one must consider a neoplasm, endocrine disorders such as hyperthyroidism or diabetes mellitus, malnutrition or malabsorption, and chronic infectious diseases such as tuberculosis or subacute bacterial endocarditis.
2. Is there fever? If there is fever, one should consider an infectious disease such as tuberculosis, subacute bacterial endocarditis, toxoplasmosis, infectious mononucleosis, or brucellosis.
3. Is there pallor? If there is pallor, the most likely cause is a type of anemia such as that associated with malabsorption syndrome or iron deficiency anemia, pernicious anemia, or anemia blood loss.
4. Is the fatigue intermittent or constant? Intermittent fatigue would make one suspect myasthenia gravis. Constant fatigue would be related to any of the conditions we have already discussed. Constant fatigue, however, with no weight loss would make one consider a psychiatric disorder.
5. Is there a positive drug or alcohol history? Alcoholism, cocaine abuse, and chronic aspirin ingestion are just a few of the disorders that can be associated with chronic fatigue. Don't forget caffeine abuse!
6. Are there associated neurologic findings? Many neurologic disorders are associated with fatigue, and they include muscular dystrophy, amyotrophic lateral sclerosis, and Parkinson's disease.
7. Is there polyuria? Polyuria would make one think of hyperthyroidism, diabetes mellitus, hyperparathyroidism, and chronic renal failure.

DIAGNOSTIC WORKUP

All patients should have routine laboratory studies, including CBC, sedimentation rate, chemistry panel, VDRL test, and a urinalysis including analysis for myoglobin. CPK, LDH, AST, and urine creatine and creatinine should be done to rule out muscle disease. A thyroid profile should be done to rule out hyperthyroidism. Further endocrine workup including serum cortisol will help differentiate Addison's disease and hypopituitarism. Because fatigue is associated with aldosteronism, a 24-hr urine aldosterone determination should be done.

Tests for chronic infectious disease, such as febrile agglutinins, brucellin antibody titer, heterophile antibody titer or Monospot test, sputum for AFB, and various skin tests for tuberculosis and fungi, can be done. HIV testing may be appropriate if there is a history of high-risk sexual behavior. Serial blood cultures also would be of value if there is significant fever. Tests for chronic organ failure such as BUN, creatinine, serum electrolytes, and liver function tests should be done. A workup of anemia including a workup of malabsorption syndrome may be necessary. Consequently, stool analysis for fat content as well as d -xylose absorption testing may be done.

A search for neoplasm will include chest x-rays, x-rays of the skull and long bones, a bone scan, an upper GI series, and small bowel follow-through as well as a barium enema and intravenous pyelogram. A muscle biopsy will help differentiate certain collagen diseases, muscular dystrophy, and trichinosis. An ANA test and serum complement to screen for collagen disease should be done. A Tensilon test may be necessary to differentiate myasthenia gravis. If a neurologic disease is suspected, referral to a neurologist would be in order. Consider EMG also. If sleep apnea is a possibility, overnight polysomnography is indicated.

If all the tests prove negative, referral to a psychiatrist would be appropriate. On the other hand, it may be appropriate to refer the patient to a psychiatrist earlier in the course of the workup. The diagnosis of chronic fatigue syndrome is sometimes made when all the diagnostic tests are negative, but whether it is truly a disease is questionable.

 

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Source: Algorithmic Diagnosis of Symptoms and Signs, 2003

ACIDOSIS (DECREASED PH): Ask the following questions:
(Algorithmic Diagnosis of Symptoms and Signs)

1. What is the blood glucose and serum acetone level? If these are increased, consider diabetic acidosis. If these are normal, consider other causes of acidosis.
2. What is the bicarbonate level? An increased bicarbonate level points to respiratory acidosis, whereas a decreased bicarbonate level points to renal disease, diarrhea, and the use of certain diuretics.

DIAGNOSTIC WORKUP

This should include a CBC, chemistry panel, electrolytes, arterial blood gas analysis, serum and urine ketones, lactic acid, pulmonary function tests, EKG, and consultation with a pulmonologist or nephrologist.

 

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Source: Algorithmic Diagnosis of Symptoms and Signs, 2003

Anemia: Differential Diagnosis
(In a Page: Signs and Symptoms)

Microcytic

• Iron deficiency
  –Most common cause of anemia
  –Due to chronic blood loss (e.g., menstrual, GI bleeding, frequent blood donation)
• Sideroblastic anemia
• Lead poisoning
• Thalassemia
• Anemia of chronic disease (often late)
  Macrocytic
• Vitamin B₁₂ or folate deficiency
  –Malabsorption
  –Poor dietary intake
  –Pernicious anemia
  –Alcohol abuse
• Liver disease
• Alcohol and medications (e.g., chemotherapeutics, HIV medications)
• Hypothyroidism
• HIV
• Myelodysplastic syndrome
• Acute leukemia
• Reticulocytosis (e.g., hemolytic anemia, production of RBCs in response to blood loss and/or vitamin B₁₂ or iron repletion)

Normocytic
• Hemorrhage, blood loss
• Anemia of chronic disease
  –Renal disease (due to decreased erythropoietin production)
  –Hypometabolic states (e.g., protein malnutrition, hypothyroidism)
• Infection
• Hemolysis (drug-induced, autoimmune, SLE, G-6PD deficiency)
• Bone marrow disease
  –Aplastic anemia
  –Bone marrow invasion (e.g., malignancy)
• Hypothyroidism
• Renal insufficiency
• Sickle cell disease
• Microangiopathy
• Membrane defects (e.g., hereditary spherocytosis)
• Disseminated intravascular coagulation
• Thrombotic thrombocytopenic purpura

Workup and Diagnosis

• Detailed history and physical examination
  –History of bleeding, past history of anemia, family history
  –Vital signs, including orthostatic blood pressure/pulse
  –Include rectal and stool guaiac
• Initial laboratory studies include CBC with red cell indices (MCV, MCHC, RDW), peripheral smear (may show characteristic cell types such as spherocytes, schistocytes, multinucleated cells), and reticulocyte count (increased if anemia is due to blood loss or RBC destruction; decreased if due to marrow failure)
• Further studies may include iron panel (iron, ferritin, transferrin saturation, TIBC), haptoglobin, vitamin B₁₂ and folate levels, bilirubin, LDH, LFTs, TSH, renal function, hemoglobin electrophoresis, bone marrow aspirate, GI workup
• Etiology may be classified based on laboratory results
  –Iron deficiency: Decreased ferritin, reticulocytes, MCV, and MCH; increased TIBC
  –Chronic disease: Decreased reticulocytes and TIBC; normal MCV and MCH
  –B₁₂ and/or folate deficiency: Decreased reticulocytes; increased MCV
  –Marrow failure: Decreased reticulocytes; may involve other cell lines
  –Hemolysis: Increased reticulocytes, bilirubin, and LDH; decreased haptoglobin in cases of intravascular hemolysis

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Source: In a Page: Signs and Symptoms, 2004

Fatigue: Differential Diagnosis
(In a Page: Signs and Symptoms)

• Infectious
  –Acute viral or bacterial infection
  –Chronic infection (e.g., subacute bacterial endocarditis, osteomyelitis, tuberculosis, HIV, viral hepatitis, mononucleosis)

Hematologic
–Anemia
–Thrombotic thrombocytopenic purpura
–Polycythemia vera

Cardiac
–Congestive heart failure
–Congenital heart disease
–Valvular heart disease
–Coronary artery disease

Pulmonary
–COPD
–Obstructive sleep apnea
–Poorly controlled asthma

Endocrine
–Hypothyroidism/hyperthyroidism
–Diabetes, types I and II
–Pregnancy
–Perimenopause
–Addison's disease

Rheumatologic
–Rheumatoid arthritis
–Systemic lupus erythematosus
–Sjögren's syndrome
–Polymyalgia rheumatica

Gastrointestinal
–Inflammatory bowel disease
–Portal hypertension (e.g., cirrhosis)

Acute or chronic renal failure

Neurologic
–Parkinson's disease
–Multiple sclerosis

Psychiatric (e.g., depression, anxiety or panic disorder, anorexia nervosa or bulimia, somatization disorder)

Malignancy

Chronic fatigue syndrome

Fibromyalgia

Tension headache

Primary obesity

Medication side effects (e.g., β-blockers, phenytoin, digitalis, antidepressants, muscle relaxants, hypnotics)

Drug intoxication or withdrawal (e.g., alcohol, opioids, benzodiazepines, barbiturates, cocaine)

Workup and Diagnosis

• Complete history and physical exam are essential, including screening for malignancy, chronic infection, chronic cardiopulmonary disease, and psychiatric disease
• Initial workup may include CBC, chemistries, glucose, calcium, urinalysis, liver function studies, TSH, stool guaiac, and age-appropriate cancer screening (e.g., PAP smear, mammography, flexible sigmoidoscopy, PSA)
• Further testing based on history and physical findings may include chest X-ray (for dyspnea, cough, abnormal lung exam), ECG (for chest pain, dyspnea), echocardiogram (heart murmur), appropriate cultures and/or serology if infection is suspected (e.g., PPD, HIV, hepatitis), malignancy workup, pregnancy test, ANA, ESR, RF, and Lyme titers
• Further testing based on abnormal initial labs may include anemia workup (reticulocyte count, iron studies, vitamin B₁₂ and folate levels, hemoglobin electrophoresis), hepatitis workup (GGTP, viral hepatitis serologies, ultrasound of the liver), renal ultrasound, bone marrow biopsy, colonoscopy, and thyroid function tests
• Appropriate imaging studies based on initial workup may include head CT/MRI, abdominal ultrasound or CT, cardiac stress testing, bone X-rays and/or bone scan

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Source: In a Page: Signs and Symptoms, 2004

Anemia: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Often multifactorial
  Hypochromic, microcytic
• Common
  –Iron deficiency
  –Thalassemias
  –Lead poisoning
• Less common: Acute infection or chronic disease, renal disease (decreased erythropoietin), sideroblastic anemia, protein-calorie malnutrition/anorexia, metabolic defects of iron metabolism

Normocytic, Normochromic
• Blood loss (acute blood loss due to trauma, occult blood loss such as GI, periodic blood loss such as occurs with menstruation)
• Marrow failure
  –Diamond-Blackfan anemia
  –Fanconi anemia
  –Transient erythroblastopenia of childhood
• Increased destruction of RBCs
  –Sickle cell disease
  –Membrane abnormalities
  –Enzyme deficiencies (G6PD, pyruvate kinase)
• Hemolysis: Drug-induced, immune
• Microangiopathic hemolytic anemia
• Hormone deficiencies (e.g., thyroid, growth)
• Acquired pure red cell aplasia
• Pregnancy/obstetric accident
• Marrow invasion or dysfunction
• Early iron deficiency
  Macrocytic
• Common
  –Vitamin B12 and/or folate deficiency
• Less common: Drug-induced, Diamond-Blackfan anemia, Fanconi anemia, congenital heart disease, Down syndrome, myelodysplastic syndromes, erythroleukemia, reticulocytosis (hemolysis, blood loss, marrow recovery), pure red cell aplasia, hypothyroidism, liver disease, metabolic disease, asplenia, spurious

Workup and Diagnosis

• Symptoms are rare unless severe and vary by age
  –Younger: Pallor, irritability, sleepiness, failure to thrive
  –Older: Shortness of breath, exercise intolerance, pallor, palpitations, syncope, headache
• History: Age, gender, race/ethnicity, gestation, blood group; strenuous exercise, previous anemia, travel, jaundice; diet history (especially high milk intake); pica, age of home (older homes used lead-based paint); dark urine, transfusions; symptoms of malignancy (fever, weight loss, night sweats, bone pain), menorrhagia
• Family history: Anemia, cholecystectomy, splenectomy
• Physical exam: Vital signs, growth; nodes, murmur, edema, liver/spleen ascites, masses; spoon nails, frontal bossing, triphalangeal thumbs, hypoplasia of thenar eminence; vibratory and position sense (for B12 deficiency); hyperpigmentation, petechiae, purpura, jaundice
• Labs: CBC, peripheral smear, RBC indices (MCV, RDW, RBC, Mentzer index); reticulocyte count, hemoglobin electrophoresis; stool for occult blood; lead level in younger children; Coombs test and haptoglobin if suspicious of blood loss; iron studies (serum iron, ferritin, total iron binding capacity, % saturation)
• Less often: Urinalysis, G6PD screen, folic acid and vitamin B12 levels, ESR, osmotic fragility
• Bone marrow exam

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Source: In A Page: Pediatric Signs and Symptoms, 2007

Fatigue: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Inadequate rest
• Excessive exercise
• Insufficient caloric intake
• Depression
• Infectious mononucleosis: Common in adolescence, typically due to EBV or CMV
• Anemia
• Hepatitis
  –Viral (e.g., HAV, HBV, HCV)
  –Consider autoimmune in adolescent girls
• Drugs
  –Antihistamines, anticonvulsants, opiates
• Obesity
  –Rapid fatigue with exertion
  –Somnolence with elevated PaCO₂is termed Pickwickian syndrome
• Tonsillar-adenoidal hypertrophy
  –Impaired air exchange while sleeping
  –Associated with restless sleeping
• Chronic fatigue syndrome
  –Controversial diagnosis
  –Underlying depression is common
• Polycythemia in neonates can be associated with cyanosis and feeding problems
• Encephalitis/meningitis
• Tuberculosis
• Brucellosis: Weight loss, low-grade fever, back pain
• Hypothyroidism
• Adrenocortical insufficiency: Often with hyperpigmentation and weakness
• Hypoglycemia
• Inflammatory bowel disease
• Juvenile rheumatoid arthritis
• Systemic lupus erythematosus
• Intussusception
• Dermatomyositis: Often with muscle weakness and pain
• Congestive heart failure: With tachypnea and dyspnea on exertion
• Pericarditis: Fatigue and dyspnea may precede friction rub
• Renal tubular acidosis
• Uremia
• Myasthenia gravis
• Malignancy

Workup and Diagnosis

• History
  –Duration of complaint
  –Sleeping habits (length of sleep, restfulness, snoring)
  –Eating habits (number of meals per day, caloric intake)
  –Psychosocial stressors
  –Associated signs and symptoms (weight change, fever,
• muscle aches, breathing difficulty, diarrhea, vomiting, sore throat)
  –Medications, including over-the-counter drugs
• Physical exam
  –Vital signs and weight
  –Oral exam for tonsillar hypertrophy, exudates, erythema
  –Palpable lymph nodes
  –Hepatomegaly with tenderness
  –Splenomegaly (seen with EBV, CMV, lymphoma)
  –Skin pallor, jaundice, cyanosis
  –Increased work of breathing, wheezes, rales
  –Cardiac exam for rubs, murmurs
  –Psychological assessment of mood and affect
• Labs
  –Consider screening CBC for anemia
  –WBC differential for atypical lymphocytes (in EBV, CMV) or blasts (in leukemia)
  –Viral serology for EBV or CMV
  –ALT and AST for hepatitis
  –TSH and free T4 for hypothyroidism
  –BUN and Cr for renal dysfunction
  –Other specific testing based on history, physical exam

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Source: In A Page: Pediatric Signs and Symptoms, 2007

Congenital Penile Anomalies: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Hypospadias
  –Most common penile anomaly
  –Incidence of 1/500
  –Urethral meatus is typically located on the ventral surface of the glans penis
  –The meatus may also be located on the ventral surface of the penile shaft, the scrotum, or the perineum
  –Frequently associated with a ventral curvature of the penis (chordee) and/or a hooded prepuce
  –Less commonly associated with undescended testes or inguinal hernia

• Epispadias
  –Less common than hypospadias
  –Urethral meatus on dorsal surface of the penis
• Chordee
  –Ventral curvature of the penis
  –Most often associated with hypospadias
  –May occur without hypospadias when the ventral tissue is hypoplastic or fibrotic
• Dorsal hood
  –Incomplete formation of the ventral foreskin
  –May occur with hypospadias

• Micropenis (microphallus)
  –Defined as stretched penis length shorter than 2 standard deviations below the mean for gestational age
  –Associated with Prader-Willi, Kallmann Laurence-Moon-Biedl syndrome, and growth hormone deficiency

Workup and Diagnosis

• History
  –Prenatal exposure to sex steroids
  –Associated anomalies or syndromic findings
  –Family history
• Physical exam
  –Careful examination of the glans penis, the penile shaft, the scrotum, and the perineum
  –Examination for syndromic features (e.g., hypotonia, small hands and feet, almond-shaped eyes in Prader-Willi)
• Labs
  –Micropenis: Gonadotropin-releasing hormone, anterior pituitary function studies
• Radiology
  –Hypospadias: VCUG is indicated if hypospadias is severe to rule out other anomalies of the urinary tract
  –Micropenis: MRI of the hypothalamus and anterior pituitary
  • Studies
    –Genetics consultation if features of Prader-Willi, Kallmann or Laurence-Moon-Biedl syndrome are present
    –Karyotype for patients in whom the genitalia are at all ambiguous

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Source: In A Page: Pediatric Signs and Symptoms, 2007

ANEMIA: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

Clinical evaluation should involve looking for occult blood in the stool, noting jaundice and splenomegaly, and taking a careful history to exclude drugs, toxins, blood loss, or nutrition as possible factors. On physical examination, one may also note a smooth tongue (pernicious anemia), spoon nails (iron deficiency anemia), and myxedema. The initial laboratory workup includes a CBC and differential, serum iron and iron-binding capacity or ferritin levels, serum B12 and folic acid levels, chemistry profile, and serum haptoglobin level. The clinician should look at a blood smear. If these studies are not revealing, a hematologist should be consulted for a bone marrow examination.

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Source: Differential Diagnosis in Primary Care, 2007

WEAKNESS AND FATIGUE, GENERALIZED: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

The association of other symptoms and signs with generalized weakness and fatigue is very important in pinning down a diagnosis. Generalized lymphadenopathy and fatigue suggest infectious mononucleosis, lymphoma, or tuberculosis or other chronic infection such as AIDS. Weakness and weight loss and polyphagia with polyuria and polydypsia would suggest hyperthyroidism or diabetes mellitus. Generalized weakness with polyuria and no significant weight loss suggests hyperparathyroidism. Weakness with pallor suggests some type of anemia. Weakness and weight loss without polyuria or polyphagia suggest malignancy or malabsorption syndrome. Weakness with other significant neurologic signs and symptoms prompts the consideration of muscular dystrophy, amyotrophic lateral sclerosis, or multiple sclerosis. Weakness with drug or alcohol use prompts the investigation of drug or alcohol abuse. Caffeine, especially in large quantities, can also cause significant weakness and chronic fatigue.

The initial workup of weakness and fatigue requires a CBC, sedimentation rate, drug screen, chemistry panel, thyroid profile, ANA, chest x-ray and ECG. If muscular dystrophy or dermatomyositis is suspected, urine for creatinine, creatine and myoglobin can be done. Ultimately, a muscle biopsy may be indicated. If myasthenia gravis is suspected, serum for acetylcholine receptor antibody may be done. If Addison disease is suspected, a serum cortisol may be done. A 24-hour urine aldosterone level may be done to exclude primary aldosteronism. Serum PTH may be done to exclude hyperparathyroidism.

It would be wise to consult an infectious disease specialist before ordering an expensive workup. It would also be wise to consult an oncologist when searching for a malignancy before ordering an expensive workup.

When all tests have negative findings, many clinicians have been tempted to make a diagnosis of chronic fatigue syndrome. It is questionable whether this is truly a disease or not.

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Source: Differential Diagnosis in Primary Care, 2007

ACIDOSIS (DECREASED PH): Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

The laboratory will be of greatest assistance in determining the cause of acidosis. An elevated blood sugar and serum acetone level will help diagnose diabetic acidosis. An elevated blood urea nitrogen (BUN) would point to uremia acidosis. Arterial blood gases may show an increased CO2, isolating pulmonary emphysema as the cause.

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Source: Differential Diagnosis in Primary Care, 2007

Fatigue: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Obtain a careful history to identify the patient’s fatigue pattern. Fatigue that worsens with activity and improves with rest generally indicates a physical disorder; the opposite pattern, a psychological disorder. Fatigue lasting longer than 4 months, constant fatigue that’s unrelieved by rest, and transient exhaustion that quickly gives way to bursts of energy are other findings associated with psychological disorders.

Ask about related symptoms and recent viral or bacterial illness or stressful changes in lifestyle. Explore nutritional habits and appetite or weight changes. Carefully review the patient’s medical and psychiatric history for chronic disorders that commonly produce fatigue. Ask about a family history of such disorders.

Obtain a thorough drug history, noting the use of any drug with fatigue as an adverse effect. Ask about alcohol and drug use patterns. Determine the patient’s risk for carbon monoxide poisoning, and inquire as to whether the patient has a carbon monoxide detector.

Observe the patient’s general appearance for overt signs of depression or organic illness. Is he unkempt or expressionless? Does he appear tired or sickly, or have a slumped posture? If warranted, evaluate his mental status, noting especially mental clouding, attention deficits, agitation, or psychomotor retardation.

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Source: Handbook of Signs & Symptoms (Third Edition), 2006

Tunnel vision [Gun barrel vision, tubular vision]: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Ask the patient when he first noticed a loss of peripheral vision, and have him describe the progression of vision loss. Ask him to describe in detail exactly what and how far he can see peripherally. Explore the patient’s personal and family history for ocular problems, especially progressive blindness that began at an early age.

To rule out malingering, observe the patient as he walks. A patient with severely limited peripheral vision typically bumps into objects (and may even have bruises), whereas the malingerer manages to avoid them.

If your examination findings suggest tunnel vision, refer the patient to an ophthalmologist for further evaluation.

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Source: Handbook of Signs & Symptoms (Third Edition), 2006

Renal tubular acidosis: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

CONFIRMING DIAGNOSIS Demonstration of impaired acidification of urine with systemic metabolic acidosis confirms distal RTA. Demonstration of bicarbonate wasting due to impaired reabsorption confirms proximal RTA.

Other relevant laboratory results show:

❑ decreased serum bicarbonate, pH, potassium, and phosphorus

❑ increased serum chloride and alkaline phosphatase

❑ alkaline pH, with low titratable acids and ammonium content in urine; increased urinary bicarbonate and potassium; low specific gravity.

In later stages, X-rays may show nephrocalcinosis.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Aplastic anemias: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Confirmation of aplastic anemia requires a series of laboratory tests:

❑ RBCs are usually normochromic and normocytic (although macrocytosis [larger-than-normal erythrocytes] and anisocytosis [excessive variation in erythrocyte size] may exist), with a total count of 1 million/µl or less. Absolute reticulocyte count is very low.

❑ Serum iron level is elevated (unless bleeding occurs), but total iron-binding capacity is normal or slightly reduced. Hemosiderin (a derivative of hemoglobin [Hb]) is present, and tissue iron storage is visible microscopically.

❑ Platelet, neutrophil, and white blood cell counts fall.

❑ Coagulation tests (bleeding time), reflecting decreased platelet count, are abnormal.

❑ Bone marrow aspiration from several sites may yield a “dry tap,” and biopsy will show severely hypocellular or aplastic marrow, with varied amounts of fat, fibrous tissue, or gelatinous replacement; absence of tagged iron (because iron is deposited in the liver rather than bone marrow) and megakaryocytes (platelet precursors); and depression of erythroid elements.

Differential diagnosis must rule out paroxysmal nocturnal hemoglobinuria and other diseases in which pancytopenia is common.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Folic acid deficiency anemia: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

The Schilling test and a therapeutic trial of vitamin B₁₂ injections distinguish between folic acid deficiency anemia and pernicious anemia. Significant findings include macrocytosis, decreased reticulocyte count, abnormal platelets, and serum folate less than 3 ng/ml.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Iron deficiency anemia: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Blood studies (serum iron levels, total iron-binding capacity, and ferritin levels) and stores in bone marrow may confirm iron deficiency anemia. However, the results of these tests can be misleading because of complicating factors, such as infection, pneumonia, blood transfusion, or iron supplements. Characteristic blood test results include:

❑ low Hb levels (in males, less than 12 g/ dl; in females, less than 10 g/dl)

❑ low hematocrit (in males, less than 39%; in females, less than 35%)

❑ low serum iron levels, with high binding capacity

❑ low serum ferritin levels

❑ low RBC count, with microcytic and hypochromic cells (in early stages, RBC count may be normal, except in infants and children)

❑ decreased mean corpuscular Hb in severe anemia.

Bone marrow studies reveal depleted or absent iron stores (done by staining) and normoblastic hyperplasia.

Diagnosis must rule out other forms of anemia, such as those that result from thalassemia minor, cancer, and chronic inflammatory, hepatic, and renal disease.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Pernicious anemia: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

A positive family history, typical ethnic heritage, and results of blood studies, bone marrow aspiration, gastric analysis, and the Schilling test establish the diagnosis. (See Tests for blood composition, production, and function, pages 1022 and 1023.) Laboratory screening must rule out other anemias with similar symptoms, such as folic acid deficiency anemia, because treatment differs. Diagnosis must also rule out vitamin B₁₂ deficiency resulting from malabsorption due to GI disorders, gastric surgery, radiation, or drug therapy.

Blood study results that suggest pernicious anemia include:

❑ decreased Hb levels (4 to 5 g/dl) and decreased RBC count

ELDER TIP Hb levels drop 1 to 2 g/ dl in elderly men, and HCT may decrease slightly in both men and women. These changes reflect decreased bone marrow and hematopoiesis and (in men) decreased androgen levels; they aren’t an indicator of pernicious anemia.

❑ increased mean corpuscular volume (greater than 120/µl); because larger-than-normal RBCs each contain increased amounts of Hb, mean corpuscular Hb concentration is also increased

❑ possible low white blood cell and platelet counts and large, malformed platelets

❑ serum vitamin B₁₂ assay levels less than 0.1 mcg/ml

❑ elevated serum lactate dehydrogenase levels.

Bone marrow aspiration reveals erythroid hyperplasia (crowded red bone marrow), with increased numbers of megaloblasts but few normally developing RBCs. Gastric analysis shows absence of free hydrochloric acid after histamine or pentagastrin injection.

Confirming diagnosis  The Schilling test is the definitive test for pernicious anemia. In this test, the patient receives a small oral dose (0.5 to 2 mcg) of radioactive vitamin B₁₂ after fasting for 12 hours. A larger dose (1 mg) of nonradioactive vitamin B₁₂ is given I.M. 2 hours later, as a parenteral flush, and the radioactivity of a 24-hour urine specimen is measured. About 7% of the radioactive B₁₂ dose is excreted in the first 24 hours; people with pernicious anemia excrete less than 3%. (In pernicious anemia, the vitamin remains unabsorbed and is passed in the stool.) When the Schilling test is repeated with IF added, the test shows normal excretion of vitamin B₁₂.

Important serologic findings may include IF antibodies and antiparietal cell antibodies.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Sickle cell anemia: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

A positive family history and typical clinical features suggest sickle cell anemia. Hb electrophoresis showing HbS or other hemoglobinopathies can also confirm it. Electrophoresis should be done on umbilical cord blood samples at birth to provide sickle cell disease screening for all neonates at risk.

Additional laboratory studies may show a low RBC count, elevated white blood cell and platelet counts, decreased erythrocyte sedimentation rate, increased serum iron, decreased RBC survival, and reticulocytosis. Hb levels may be low or normal. During early childhood, palpation may reveal splenomegaly, but, as the child grows older, the spleen shrinks.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Sideroblastic anemias: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Confirming diagnosis  Ringed sideroblasts on microscopic examination of bone marrow aspirate, stained with Prussian blue or alizarin red dye, confirm this diagnosis. (See Ringed sideroblast.)

Microscopic examination of blood shows erythrocytes to be hypochromic or normochromic and slightly macrocytic. Red cell precursors may be megaloblastic, with anisocytosis (abnormal variation in red blood cell [RBC] size) and poikilocytosis (abnormal variation in RBC shape). Unlike iron deficiency anemia, sideroblastic anemia lowers Hb levels and raises serum iron and transferrin levels. In turn, faulty Hb production raises urobilinogen and bilirubin levels. Platelets and leukocytes remain normal, but, occasionally, thrombocytopenia or leukopenia occurs.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Chronic fatigue syndrome: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Because the cause and nature of CFS are still unknown, no single test unequivocally confirms its presence. Therefore, physicians base this diagnosis on the patient’s history and the CDC’s criteria. (See CDC criteria for diagnosing chronic fatigue syndrome.) Because the CDC criteria are admittedly a working concept that may not include all forms of this disease and are based on symptoms that can result from other diseases, diagnosis is difficult and uncertain.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Fatigue: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Obtain a careful history to identify the patient’s fatigue pattern. Fatigue that worsens with activity and improves with rest generally indicates a physical disorder; the opposite pattern, a psychological disorder. Fatigue lasting longer than 4 months, constant fatigue that’s unrelieved by rest, and transient exhaustion that quickly gives way to bursts of energy are findings associated with psychological disorders.

Ask about related symptoms and any recent viral or bacterial illness or stressful changes in lifestyle. Explore nutritional habits and any appetite or weight changes. Carefully review the patient’s medical and psychiatric history for any chronic disorders that commonly produce fatigue, and ask about a family history of such disorders.

Obtain a thorough drug history, noting use of any narcotic or drug with fatigue as an adverse effect. Ask about alcohol and drug use patterns. Determine the patient’s risk of carbon monoxide poisoning, and ask whether the patient has a carbon monoxide detector.

Observe the patient’s general appearance for overt signs of depression or organic illness. Is he unkempt or expressionless? Does he appear tired or sickly, or have a slumped posture? If warranted, evaluate his mental status, noting especially mental clouding, attention deficits, agitation, or psychomotor retardation.

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Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Tunnel vision [Gun barrel vision, tubular vision]: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Ask the patient when he first noticed a loss of peripheral vision, and have him describe the progression of vision loss. Ask him to describe in detail exactly what and how far he can see peripherally. Explore the patient’s personal and family history for ocular problems, especially progressive blindness that began at an early age.

To rule out malingering, observe the patient as he walks. A patient with severely limited peripheral vision typically bumps into objects (and may even have bruises), whereas a malingerer manages to avoid them.

If your examination findings suggest tunnel vision, refer the patient to an ophthalmologist for further evaluation.

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Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Fatigue: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

A thorough medical, social, and family history must be conducted to identify comorbid or contributing conditions that require treatment or suggest lifestyle modification.

A. The fatigue should be assessed in terms of duration, onset, level of impairment, and character. Specifically, fatigue should be distinguished from weakness and hypersomnolence.

B. A complete review of systems may point to a cardiovascular, neurologic, psychiatric, infectious, autoimmune, hematologic, pulmonary, endocrine, or malignant cause to pursue.

 C. Attention should also be given to medication—both prescription and over-the-counter—and to diet, exercise, substance abuse, and sleep disturbance.

 D. Lifestyle issues to explore include caretaking for young children, an elderly or ill relative, and the number of hours worked outside the home. Life stresses or major family transitions such as relocation, death, divorce, financial difficulties and past or current abuse or trauma should also be assessed.

Physical examination

A thorough physical examination should be done to investigate findings of underlying disease. This is also an important prerequisite to satisfy the patient’s concern regarding the possibility of an organic cause if a psychiatric diagnosis is made. Particular attention should be given to the presence of pallor, cardiac arrhythmia, dyspnea, fever or other indication of infection; weight loss; lymphadenopathy; evidence of inflammatory arthritis, occult blood loss, organomegaly, or abdominal masses; neurologic signs of impaired coordination; hypertension; edema; generalized pruritus; obesity; peripheral neuropathy; goiter; dry hair or skin; hemoptysis; or pregnancy. Conduct a mental status examination to identify abnormalities in mood, intellectual function, memory, and personality. Pay special attention to assessment of symptoms of depression or anxiety, suicidal ideation, and psychomotor retardation.

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Source: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, 2000

Anemia: Differential Overview
(Field Guide to Bedside Diagnosis)

❑ Iron deficiency

❑ Chronic disease

❑ Vitamin B₁₂ deficiency

❑ Subacute blood loss

❑ Thalassemia trait

❑ Folate deficiency

❑ Sickle cell trait

❑ Immune hemolytic anemia

❑ Myeloproliferative disease

❑ Aplastic anemia

❑ Sideroblastic anemia

Diagnostic Approach

Symptoms include dyspnea on exertion, fatigue, headache, palpitations, difficulty concentrating, and tinnitus. When blood loss occurs gradually, oxygen delivery can be maintained at rest to a hemoglobin as low as 5 g/dL.

Tachycardia and a systolic flow murmur occur when hemoglobin is less than 7.5 g/dL. Pallor is found in the conjunctivae and notably in the palmar creases with hand extension (they normally flush). Press the base of the nail to observe blanching and flushing, comparing with the color of your own nailbeds. Always test for orthostatic blood pressure changes to assess acuteness of blood loss. Check stools for occult blood. Splenomegaly is found in hemolysis, pernicious anemia, liver diseases, infection, and thalassemia. In chronic anemia, there will be bounding pulses with a wide pulse pressure and a midsystolic
murmur.

Heavy menses are recognized by clots and gushing of blood with tampon removal. A family history of anemia suggests hemoglobinopathy (e.g., sickle cell anemia or thalassemia). Drug or toxin exposure suggests aplastic anemia, myelodysplasia, or G6PD hemolysis. Glossitis is seen with iron, folate, or vitamin B₁₂ deficiency. Lymphadenopathy is seen with marrow infiltration or infection.

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Source: Field Guide to Bedside Diagnosis, 2007

Fatigue: Differential Overview
(Field Guide to Bedside Diagnosis)

❑ Infectious mononucleosis

❑ Depression

❑ Diabetes

❑ Hypothyroidism

❑ Drugs

❑ Chronic sleep deprivation

❑ Congestive heart failure

❑ Occult infection

❑ Iron deficiency anemia

❑ Obstructive sleep apnea

❑ Renal failure

❑ Chronic fatigue syndrome

❑ Cushing syndrome

❑ Occult cancer

❑ Addison disease

❑ Myasthenia gravis

Diagnostic Approach

Organic fatigue is characterized by physical weakness or exhaustion, which is exacerbated by activity and partially relieved by sleep, short duration (,2 months), unintentional weight loss of greater than 10%, and an ill appearance. Most organic causes have associated signs and symptoms, specific and few in number.

Psychological fatigue is characterized by a primary inertia to initiation of physical activity, which when undertaken, can be performed. The patient is tired all the time, but fatigue is not exacerbated by exertion or relieved by rest. A protracted course, multiple and nonspecific associated symptoms, relation to stressful life events, and an anxious or depressed appearance are other clues. The sick role response to prior minor illness can indicate likely response to the current illness.

A medical or psychiatric diagnosis can be found in over two-thirds of patients with more than one month of fatigue. Psychiatric diagnoses, especially depression, panic disorder, or somatization disorder are the most common.

A diagnostic approach that involves careful history-taking and physical examination, assiduous avoidance of early closure, and a clear orientation to the reality of the patient’s perceptions whatever the cause (i.e., never implying “It’s all in your head”), is most rewarding. The differential is wide, and identification of the unusual organic causes among the many psychophysiological ones takes great skill.

---

Sign	Sensitivity	Specificity	Likelihood Ratio
Hypothyroidism
Coarse skin	29	95	5.6
Cool dry skin	16	97	4.7
Periorbital puffiness	53	81	2.8
Enlarged thyroid	46	84	2.8
Lateral eyebrow hair loss	29	85	1.9

---

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Source: Field Guide to Bedside Diagnosis, 2007

Renal tubular acidosis: Diagnosis
(Handbook of Diseases)

Demonstration of impaired urine acidification with systemic metabolic acidosis confirms distal RTA. Demonstration of bicarbonate wasting from impaired reabsorption confirms proximal RTA.

Other relevant laboratory results show the following:

❑ decreased serum bicarbonate, pH, potassium, and phosphorus levels

❑ increased serum chloride and alkaline phosphatase levels

❑ alkaline pH, with low titratable acids and ammonium content in urine; and increased urinary bicarbonate and potassium levels, with low specific gravity.

In later stages, X-rays may show nephrocalcinosis.

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Source: Handbook of Diseases, 2003

Aplastic and hypoplastic anemias: Diagnosis
(Handbook of Diseases)

Confirmation of aplastic anemia requires a series of laboratory tests:

RBCs are usually normochromic and normocytic (although macrocytosis [larger-than-normal erythrocytes] and anisocytosis [excessive variation in erythrocyte size] may exist), with a total count of 1 million/µl or less. Absolute reticulocyte count is low.

Serum iron level is elevated (unless bleeding occurs), but total iron-binding capacity is normal or slightly reduced. Hemosiderin is present, and tissue iron storage is visible microscopically.

Platelet, neutrophil, and white blood cell counts fall.

Coagulation test results (bleeding time), reflecting decreased platelet count, are abnormal.

Bone marrow aspiration from several sites may yield a “dry tap,” and a biopsy will show severely hypocellular or aplastic marrow, with varied amounts of fat, fibrous tissue, or gelatinous replacement; absence of tagged iron (because iron is deposited in the liver rather than in bone marrow) and megakaryocytes; and depression of erythroid elements.

A differential diagnosis must rule out paroxysmal nocturnal hemoglobinuria and other diseases in which pancytopenia is common.

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Source: Handbook of Diseases, 2003

Chronic fatigue and immune dysfunction syndrome: Diagnosis
(Handbook of Diseases)

The cause and nature of CFIDS are still unknown, and no single test unequivocally confirms its presence. Therefore, the diagnosis is based on the patient’s history and the CDC criteria. Because the CDC criteria are admittedly a working concept that may not include all forms of this disease and are based on symptoms that can result from other diseases, diagnosis is difficult and uncertain. Considerable overlap exists between CFIDS and fibromyalgia syndrome, with many patients having features of both.

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Source: Handbook of Diseases, 2003

Folic acid deficiency anemia: Diagnosis
(Handbook of Diseases)

The Schilling test and a therapeutic trial of vitamin B₁₂ injections help distinguish between folic acid deficiency anemia and pernicious anemia. Significant findings include macrocytosis, a decreased reticulocyte count, low platelet count, and a serum folate level less than 4 mg/ml.

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Source: Handbook of Diseases, 2003

Iron deficiency anemia: Diagnosis
(Handbook of Diseases)

Blood studies (serum iron, total iron-binding capacity, and ferritin levels) and stores in bone marrow may confirm iron deficiency anemia. However, the results of these tests can be misleading because of complicating factors, such as infection, pneumonia, blood transfusion, and iron supplements. Characteristic blood study results include:

❑ low Hb levels (males, less than 12 g/dl; females, less than 10 g/dl)

❑ low hematocrit (males, less than 47 ml/dl; females, less than 42 ml/dl)

❑ low serum iron levels, with high iron-binding capacity

❑ low serum ferritin levels

❑ low RBC count, with microcytic and hypochromic cells (in early stages, RBC count may be normal, except in infants and children)

❑ decreased mean corpuscular Hb level (in patients with severe anemia).

Bone marrow studies reveal depleted or absent iron stores (done by staining) and normoblastic hyperplasia.

The diagnosis must rule out other forms of anemia, such as those that result from thalassemia minor, cancer, and chronic inflammatory, liver, and kidney disease.

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Source: Handbook of Diseases, 2003

Pernicious anemia: Diagnosis
(Handbook of Diseases)

A positive family history, typical ethnic heritage, and results of blood studies, bone marrow aspiration, gastric analysis, and the Schilling test help establish the diagnosis of pernicious anemia. Laboratory screening must rule out other anemias with similar symptoms, such as folic acid deficiency anemia, because treatment differs.

Diagnosis must also rule out vitamin B₁₂ deficiency resulting from malabsorption due to a GI disorder, gastric surgery, radiation, or drug therapy.

Blood study results that suggest pernicious anemia include:

❑ decreased Hb level (4 to 5 g/dl) and decreased RBC count

❑ increased mean corpuscular volume (greater than 120/µl), because each larger-than-normal RBC contains increased amounts of Hb; mean corpuscular Hb concentration is also increased

❑ low white blood cell and platelet counts and large, malformed platelets

❑ serum vitamin B₁₂–assay levels, less than 0.1 mcg/ml

❑ elevated serum lactate dehydrogenase levels.

Bone marrow aspiration reveals erythroid hyperplasia (crowded red bone marrow), with increased numbers of megaloblasts but few normally developing RBCs. Gastric analysis shows the absence of free hydrochloric acid after histamine or pentagastrin injection.

Schilling test

With the Schilling test, the definitive test for pernicious anemia, the patient receives a small oral dose (0.5 to 2 mcg) of radioactive vitamin B₁₂ after fasting for 12 hours. A larger dose (1 mg) of nonradioactive vitamin B₁₂ is given I.M. 2 hours later, as a parenteral flush, and the radioactivity of a 24-hour urine specimen is measured.

Usually, about 7% of the radioactive vitamin B₁₂ dose is excreted in the first 24 hours; persons with pernicious anemia excrete less than 3%. (With pernicious anemia, the vitamin remains unabsorbed and is passed in the stool.) When the Schilling test is repeated with IF added, the test shows normal excretion of vitamin B₁₂.

Serologic tests

Important serologic findings may include IF antibodies and antiparietal cell antibodies.

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Source: Handbook of Diseases, 2003

Sickle cell anemia: Diagnosis
(Handbook of Diseases)

A positive family history and typical clinical features suggest sickle cell anemia. Hb electrophoresis showing Hb S or other hemoglobinopathies can confirm it. Electrophoresis should be done on umbilical cord blood samples at birth to provide sickle cell disease screening for all neonates at risk.

Additional laboratory studies show a low RBC count, elevated white blood cell and platelet counts, decreased erythrocyte sedimentation rate, increased serum iron level, decreased RBC survival, and reticulocytosis. Hb may be low or normal.

During early childhood, palpation may reveal splenomegaly, but as the child grows older, the spleen shrinks.

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Source: Handbook of Diseases, 2003

Sideroblastic anemias: Diagnosis
(Handbook of Diseases)

Ringed sideroblasts on microscopic examination of bone marrow aspirate, stained with Prussian blue or alizarin red dye, confirm the diagnosis.

Microscopic examination of blood shows hypochromic or normochromic, and slightly macrocytic, erythrocytes. Red blood cell (RBC) precursors may be megaloblastic, with anisocytosis (abnormal variation in RBC size) and poikilocytosis (abnormal variation in RBC shape).

Unlike iron deficiency anemia, sideroblastic anemia lowers Hb and raises serum iron and transferrin levels. In turn, faulty Hb production raises urobilinogen and bilirubin levels. Platelet and leukocyte levels remain normal, but thrombocytopenia or leukopenia occasionally occurs.

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Source: Handbook of Diseases, 2003

Fatigue: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Obtain a careful history to identify the patient’s fatigue pattern. Fatigue that worsens with activity and improves with rest generally indicates a physical disorder; the opposite pattern indicates a psychological disorder. Fatigue lasting longer than 4 months, constant fatigue that’s unrelieved by rest, and transient exhaustion that quickly gives way to bursts of energy are other findings associated with psychological disorders.

Ask about related symptoms and any recent viral or bacterial illness or stressful changes in lifestyle. Explore nutritional habits and any appetite or weight changes. Carefully review the patient’s medical and psychiatric history for chronic disorders that commonly produce fatigue. Ask about a family history of such disorders.

Obtain a thorough drug history, noting use of any opioid or drug with fatigue as an adverse effect. Ask about alcohol and drug use patterns. Determine the patient’s risk of carbon monoxide poisoning, and inquire as to whether the patient has a carbon monoxide detector.

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Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Fatigue: Clinical Features and Diagnosis
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Physiologic Causes

Children who lack sleep and rest, have decreasedcaloric intake, and engage in strenuous or prolonged exercise arelikely to experience fatigue.

Pathologic Causes

Anemia

Any typeof anemia can produce fatigue.

Pallor is usually evident with moderate-to-severeanemia.

CBC should be performed as screeningtest.

Infection

Any acute or chronic infection can producefatigue. Common infections that are often associated with prolongedor severe fatigue include infectious mononucleosis, influenza, hepatitisA, tuberculosis, and endocarditis.

Chronic Disease

Fatigue often occurs with cardiac disease(cardiac failure, cyanotic congenital heart disease, pulmonary vasculardisease), pulmonary disease (asthma, cystic fibrosis), chronic renaldisease, inflammatory bowel disease, chronic liver disease, collagenvascular disease, endocrine disorders (hypothyroidism, hyperthyroidism,adrenal insufficiency), muscle disorders that cause weakness, malnutrition,and malignancy.

Allergic Disease

Children with allergic rhinitis (seasonalor perennial) or asthma often experience fatigue, until their symptomsare relieved.

Chronic Fatigue Syndrome

Revisedcase definition of this syndrome was proposed by Fukada et al. (1994).

Characterized by unexplained persistentor relapsing fatigue for >6 mos that seriously interfereswith normal activities. Not related to ongoing exertion nor is itsubstantially relieved by rest.

≥4 of the following symptoms musthave persisted or recurred during 6-mo period and must not havepredated fatigue: sore throat; tender cervical or axillary adenopathy;muscle pain; pain in multiple joints without swelling or redness;headaches of new type, pattern, or severity; awakening from sleepstill tired; malaise lasting >24 hrs after exertion; andimpaired short-term memory or concentration.

Diagnosis is clinical.

Drugs

Fatigue is common side effect of many drugs,including antihistamines, anticonvulsants, tranquilizers, and opiates.

Psychologic

Psychologicdisturbances (e.g., anxiety, depression, grief reaction, schoolphobia, or somatization disorder) can cause fatigue.

History and clinical observation areusually diagnostic.

Diagnostic Approach

When childcomplains of fatigue, history and physical exam are often diagnostic.

CBC can screen for anemia.

Monospot test can confirm diagnosisof infectious mononucleosis, but if result is negative, Epstein-Barrvirus IgG and IgM antibodies can be performed.

Psychosocial history is most importantdiagnostic tool for psychologic problems.

If diagnosis remains uncertain, initialscreening investigations for chronic disease include sedimentationrate; stool guaiac; serum electrolytes, glucose, creatinine, aminotransferases;blood urea nitrogen; UA; chest radiography; and intermediate-strengthtuberculin skin test.

Other investigations depend on suspecteddiagnosis and results of these tests.

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Source: The Diagnostic Approach to Symptoms and Signs in Pediatrics, 2006

Pallor (Anemia): Clinical Features and Diagnosis
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Disorders of Decreased Red Cell or Hemoglobin Production

Nutritional Deficiencies

Iron Deficiency

Most commoncause of anemia in children is iron deficiency. Decreased iron intake andsignificant blood loss are usual mechanisms. Iron deficiency ismost common in children <2 yrs of age and in adolescence.In preterm infants, it can occur as early as 2 mos of age, whereasin term infants it is most common at 6 mos–2 yrs of age.Peak incidence is 10–15 mos of age.

Iron deficiency usually evolves throughsuccession of stages before anemia develops.

Depletion of storage iron occurs infirst stage, and low serum ferritin (<10 g/dL)reflects diminished stores. Even with this loss in iron reserves,iron supply for red cells is adequate.

In second stage, iron supplied to redcells is low. Although mean corpuscular volume (MCV) is lower thannormal and free erythrocyte porphyrin (FEP) is higher than normal,blood Hgb remains in normal range.

In third and final stage, iron deficiencyanemia occurs and blood Hgb is lower than normal for age.

Mild iron deficiency is usually diagnosedon the basis of dietary history and lab screening.

Clinical manifestations of iron deficiencyanemia include decreased exercise tolerance, fatigue, irritability,anorexia, and pallor. Tachycardia and cardiomegaly occur when anemiais severe.

Diagnosis of iron deficiency anemiais based on history of decreased iron intake or significant bloodloss, lower than normal blood Hgb, low MCV, and presence of microcytichypochromic red cells on blood smear.

Therapeutic trial of iron (4–6mg/kg/day of elemental iron) can be given andHgb rechecked in 1 mo. Iron should be given for ≥1–2mos after blood Hgb and MCV have returned to normal in order toreplenish iron stores.

Brugnara et al. (1999) have reportedthat reticulocyte Hgb content is lower in children with iron deficiencycompared with normal children. In the future, this test may be analternative to biochemical iron studies now used in diagnosis.

Folic Acid Deficiency

Folic acidand vitamin B₁₂ deficiencies account for >95% of megaloblasticanemias. Presence of macrocytes in blood and megaloblasts in bonemarrow characterize this type of anemia.

Common causes of folate deficiencyare inadequate intake (malnutrition, sustained boiling as methodof cooking, goat milk feeding, unusual diets); defective absorption(malabsorption disorders); increased requirements (chronic hemolyticanemias, leukemia, lymphoma); and drugs (trimethoprim-sulfisoxazole,phenytoin).

Clinical features include pallor, lassitude,fatigue, anorexia, glossitis, and splenomegaly. Blood smear showsnormochromic macrocytes, hypersegmented polymorphonuclear leukocytes(≥5 lobes), anisocytosis, and poikilocytosis.

Serum folate level of <3 ng/mLindicates folic acid deficiency.

Vitamin B₁₂ Deficiency

Decreasedintake and intestinal malabsorption are common causes of vitamin B₁₂ deficiency.Deficiency of intrinsic factor and congenital defects in vitamin B₁₂ metabolismare rare.

Onset of vitamin B₁₂ deficiencyis insidious, with findings similar to those for folate deficiency.Infrequent findings include peripheral neuropathy with loss of positionand vibration sense, paresthesias, and ataxia.

Blood smear and bone marrow findingsare same as those with folate deficiency. Serum vitamin B₁₂ levelof <100 pg/mL indicates vitamin B₁₂ deficiency.Then the precise cause must be determined.

The Schilling test measures the availabilityof intrinsic factor and the intestinal phase of vitamin B₁₂ absorption.After radioactive vitamin B₁₂ (0.5–2.0 μg)is given orally, nonradioactive vitamin B₁₂ (1mg) is given 2 hrs later as an intramuscular injection, and urineis collected for 24 hrs. In normal individuals, urinary excretionis 10–35% of radioactive dose, whereas those withvitamin B₁₂ malabsorption excrete <3%.A repeat Schilling test, in which commercial intrinsic factor isadministered along with oral radioactive vitamin B₁₂,bypasses a defect in intrinsic factor, so that vitamin B₁₂ canbe absorbed in those with intrinsic factor deficiency. If intestinalmalabsorption is present, vitamin B₁₂ malabsorptionpersists even when intrinsic factor is given.

Assays for intrinsic factor in gastricjuice and antibodies to parietal cells and intrinsic factor areuseful tests when intrinsic factor deficiency is suspected.

Hypoplastic or Aplastic Anemias

Pure Red Cell Aplasia

Congenital Hypoplastic Anemia (Diamond-Blackfan Anemia)

Onset isusually in first few months of life, and anemia can be severe.

Blood smear shows normocytes or macrocytes,and reticulocyte count is low.

Diagnostic bone marrow aspirate showsdecreased numbers of red cell precursors.

Transient Erythroblastopenia of Childhood

Althoughthe cause of this disorder is uncertain, it is often associatedwith recent viral infection. Affected children are usually 6 mos–6yrs of age.

Blood smear shows normochromic normocyticred cells. Reticulocyte count is low, and Coombs test is negative.Bone marrow exam shows decrease or absence of red cell precursorsinitially and hyperplasia of red cells during recovery.

Anemia Associated with Systemic Disease

Acquired red cell aplasia may be associatedwith infection (parvovirus B19 infection, viral hepatitis, infectiousmononucleosis, endocarditis), chronic inflammatory disorders (juvenilerheumatoid arthritis, ulcerative colitis), endocrine disorders (hypothyroidism,hyperthyroidism), protein-calorie malnutrition, and chronic renaldisease.

Drug-Related

Red cell aplasia may be due to drugs (e.g.,phenytoin, carbamazepine, chloramphenicol, sulfonamides, and azathioprine).

Aplastic Anemia

Congenital

Fanconianemia is autosomal-recessive disorder that affects all bone marrowelements.

Specific physical findings usuallyexist, but this is not always the case. Findings include characteristicfacies (broad nasal base, epicanthal folds, micrognathia), skinpigment changes (café au lait spots, hyperpigmentation),microcephaly, small stature, abnormal thumbs (absent, hypoplastic,duplication), kidney malformations (absent, ectopic, duplication),and mental retardation.

Blood smear shows normochromic macrocytesand decreased numbers of leukocytes and platelets.

Specific diagnostic test is chromosomebreakage analysis that shows high proportion of cells with chromosomalbreaks, gaps, rearrangements, and exchanges.

Acquired

Common causesof acquired aplastic anemia are idiopathic (about 50%),drugs (chloramphenicol), chemical exposure (benzene, pesticides),viral infection (parvovirus, B19, Epstein-Barr virus, HIV), andradiation.

Blood count reveals pancytopenia, andbone marrow aspirate or biopsy is confirmatory.

Malignancy

Anemia maybe the presenting feature of malignancy in childhood. Associatedmanifestations suggestive of malignancy include fever, lymphadenopathy,hepatosplenomegaly, purpura, extremity pain, and abdominal mass.

Most common malignancy in childhoodis acute lymphoblastic leukemia with onset usually at 2–6yrs. Common findings include lymphadenopathy, hepatosplenomegaly,and pancytopenia. Blood smear usually shows lymphoblasts, and bonemarrow aspirate confirms diagnosis.

Neuroblastoma and lymphoma are othercommon malignancies involving bone marrow (see Chap. 1, Abdominal Masses,and Chap. 38, Lymphadenopathy).

Abnormal Heme and Globin Synthesis

Thalassemias

Are a groupof inherited anemias caused by mutations affecting synthesis of Hgb.

In alpha-thalassemias, production ofalpha-globin chains is deficient, whereas in beta-thalassemias,production of beta-globin chains is deficient.

Alpha-Thalassemias

4 alpha-globingenes exist in each individual, 2 from chromosome 16 of each parent.

In African-Americans, virtually allalpha-thalassemia syndromes involve 1-gene deletion in 1 or bothparents. 1 single-gene deletion produces silent carrier, whereas2 single-gene deletions produce alpha-thalassemia trait.

Hgb H occurs from inheritance of singledeletion from 1 parent and double deletion from the other. Inheritanceof double deletion from both parents produces hydrops fetalis.

Anemia does not occur with single-genedeletion (silent carrier), although cord blood may show 1–2% HgbBarts. After 6 mos of age, Hgb Barts disappears, and Hgb electrophoresispattern is Hgb AA.

Deletion of 2 alpha-globin genes producesalpha-thalassemia trait, and Hgb Barts may reach levels of 5–10%.There is mild microcytic hypochromic anemia.

Deletion of 3 alpha-globin genes resultsin production of Hgb H (beta-4), which gradually replaces 20–40% HgbBarts. Hemolytic anemia occurs in neonatal period, and Hgb electrophoresisconfirms diagnosis.

No alpha chains are produced with deletionof all 4 alpha-globin genes. Hgb electrophoresis shows mainly HgbBarts, Hgb H, and small amounts of Hgb Portland. Blood smear showsmicrocytosis, hypochromia, target cells, and increased number ofnucleated red cells. Usual clinical consequence is severe anemia,cardiac failure, and death in utero or few hours after birth. Afew individuals have been treated successfully with exchange transfusions,but they remain transfusion dependent.

Beta-Thalassemias

2 beta-globingenes exist on chromosome 11 in each individual. Defect of 1 beta-globingene produces heterozygous beta-thalassemia, whereas defect in 2of them produces homozygous beta-thalassemia.

In heterozygous beta-thalassemia (beta-thalassemiatrait), Hgb A₂ or Hg F or both are usuallyincreased, although occasionally these levels can be normal. Peripheralsmear shows hypochromic microcytic red cells, target cells, andbasophilic stippling.

Homozygous beta-thalassemia (beta-thalassemiamajor) usually presents with severe anemia between 6 and 12 mosof age, when normal postnatal decrease in gamma-chain synthesis(Hgb F) reveals defect in beta-chain production. Hgb concentrationsare 3–7 g/dL. Pallor, irritability, anorexia,and hepatosplenomegaly are usually found. Blood smear usually showsmicrocytic hypochromic red cells, target cells, increased numbersof nucleated red cells, and basophilic stippling. Quantitative Hgbelectrophoresis before transfusion shows Hgb A (0–80%),Hgb A₂ (2–7%), and HgbF (20–100%), depending on specific genotype. Reticulocytecount rarely exceeds 5%.

Sideroblastic Anemias

Group ofgenetic and acquired disorders characterized by anemia, low reticulocyte count,and ineffective erythropoiesis. In the genetic types, usual inheritancepattern is X-linked.

Causes of acquired sideroblastic anemiaare drugs (chloramphenicol, isoniazid), lead poisoning, and idiopathic.

Red cells are usually normochromicand normocytic, but occasionally they may be hypochromic and microcytic.Thrombocytopenia and neutropenia commonly occur. Bone marrow usually showsmarked hyperplasia of red cells and ringed sideroblasts (iron granulesin ring around nucleus of normoblasts).

Lead Poisoning

Should besuspected in any child with pica who lives in house painted withlead-based paint before 1950.

Although lead impairs uptake and utilizationof iron and production of globin in red cells, significant anemia(microcytic) is unusual unless blood lead level is >50–60μg/dL.

Blood lead level is diagnostic.

Disorders of Increased Red Cell Destruction (Hemolytic Anemias)

Hemoglobinopathies

Virtually all hemoglobinopathies with exceptionof beta-thalassemia trait can be detected by Hgb electrophoresisof cord blood. Table 45.1 listscord blood and adult Hgb electrophoresis patterns of most commonhemoglobinopathies.>>>>>

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Source: The Diagnostic Approach to Symptoms and Signs in Pediatrics, 2006

Fatigue: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

Obtain a careful history to identify the patient's fatigue pattern. Fatigue that worsens with activity and improves with rest generally indicates a physical disorder; the opposite pattern, a psychological disorder. Fatigue lasting longer than 4 months, constant fatigue that's unrelieved by rest, and transient exhaustion that quickly gives way to bursts of energy are other findings associated with psychological disorders.

Ask about related symptoms and recent viral or bacterial illness or stressful changes in lifestyle. Explore nutritional habits and appetite or weight changes. Carefully review the patient's medical and psychiatric history for chronic disorders that commonly produce fatigue. Ask about a family history of such disorders.

Obtain a thorough drug history, noting the use of any drug with fatigue as an adverse effect. Ask about alcohol and drug use patterns. Determine the patient's risk of carbon monoxide poisoning, and inquire as to whether the patient has a carbon monoxide detector in the home.

Observe the patient's general appearance for overt signs of depression or organic illness. Is he unkempt or expressionless? Does he appear tired or sickly, or have a slumped posture? If warranted, evaluate his mental status, noting especially mental clouding, attention deficits, agitation, or psychomotor retardation.

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Source: Nursing: Interpreting Signs and Symptoms, 2007

Tunnel vision [Gun barrel vision, tubular vision]: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

Ask the patient when he first noticed a loss of peripheral vision, and have him describe the progression of vision loss. Ask him to describe in detail exactly what and how far he can see peripherally. Explore the patient's personal and family history for ocular problems, especially progressive blindness that began at an early age.

To rule out malingering, observe the patient as he walks. A patient with severely limited peripheral vision typically bumps into objects (and may even have bruises), whereas the malingerer manages to avoid them.

If your examination findings suggest tunnel vision, refer the patient to an ophthalmologist for further evaluation.

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Source: Nursing: Interpreting Signs and Symptoms, 2007

ANEMIA: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

Clinical evaluation should involve looking for occult blood in the stool, noting jaundice and splenomegaly, and taking a careful history to exclude drugs, toxins, blood loss, or nutrition as possible factors. On physical examination, one may also note a smooth tongue (pernicious anemia), spoon nails (iron deficiency anemia), and myxedema. The initial laboratory workup includes a CBC and differential, serum iron and iron-binding capacity or ferritin levels, serum B₁₂ and folic acid levels, chemistry profile, and serum haptoglobin level. The clinician should look at a blood smear. If these studies are not revealing, a hematologist should be consulted for a bone marrow examination.

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Source: Differential Diagnosis in Primary Care, 2007

WEAKNESS AND FATIGUE, GENERALIZED: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

The association of other symptoms and signs with generalized weakness and fatigue is very important in pinning down a diagnosis. Generalized lymphadenopathy and fatigue suggest infectious mononucleosis, lymphoma, or tuberculosis or other chronic infection such as acquired immunodeficiency syndrome (AIDS). Weakness, weight loss, and polyphagia with polyuria and polydipsia would suggest hyperthyroidism or diabetes mellitus. Generalized weakness with polyuria and no significant weight loss suggests hyperparathyroidism. Weakness with pallor suggests some type of anemia. Weakness and weight loss without polyuria or polyphagia suggest malignancy or malabsorption syndrome. Weakness with other significant neurologic signs and symptoms prompts the consideration of muscular dystrophy, amyotrophic lateral sclerosis, or multiple sclerosis. Weakness with drug or alcohol use prompts the investigation of drug or alcohol abuse. Caffeine, especially in large quantities, can also cause significant weakness and chronic fatigue. The initial workup of weakness and fatigue requires a CBC, sedimentation rate, drug screen, chemistry panel, thyroid profile, ANA, chest x-ray, and echocardiogram (ECG). If muscular dystrophy or dermatomyositis is suspected, urine tests for creatinine, creatine, and myoglobin can be done. Ultimately, a muscle biopsy may be indicated. If myasthenia gravis is suspected, serum for acetylcholine receptor antibody may be done. If Addison disease is suspected, a serum cortisol test may be done. A 24-hour urine aldosterone level may be done to exclude primary aldosteronism. Serum parathyroid hormone (PTH) may be done to exclude hyperparathyroidism. It would be wise to consult an infectious disease specialist before ordering an expensive workup. It would also be wise to consult an oncologist when searching for a malignancy before ordering an expensive workup. When all tests have negative findings, many clinicians have been tempted to make a diagnosis of chronic fatigue syndrome. It is questionable whether this is truly a disease or not.

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Source: Differential Diagnosis in Primary Care, 2007

ACIDOSIS (DECREASED pH): Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

The laboratory will be of greatest assistance in determining the cause of acidosis. An elevated blood sugar and serum acetone level will help diagnose diabetic acidosis. An elevated blood urea nitrogen (BUN) level would point to uremia acidosis. Arterial blood gases may show an increased CO₂, isolating pulmonary emphysema as the cause.

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Source: Differential Diagnosis in Primary Care, 2007

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