An eighteen year old woman was brought to the hospital after a syncopal attack. She had fainted after carrying a heavy load of washed clothes in the morning. She was dizzy but conscious on reaching the hospital 2 hours later. She had recovered in a few minutes after falling to the ground, had not had any convulsive movements and had not hit her head on falling. She reported no diarrhea, loss of appetite, headache, jaundice, fever or muscle aches and pains. She had vomiting soon after meals, this has started 2 months ago and the vomitus contained recently eaten food. She lived in a slum area in Karachi with a widowed mother and two young brothers. The family lived below the poverty line. She was unmarried and had had her usual monthly menstruation. On examination her major finding was anemia.
She was asked by the candidate who was taking the history, whether she ate meat in her diet. She replied “When I can get it”,
“But can you eat it”
“Yes I can eat it”.
The right question should have been “Can your family afford to eat meat, chicken daal every day , once a week or only once or twice a month?”. The family lived off chapati, rice and leafy vegetables like herbs mostly so there was a strong element of malnutrition in the history. This was missed because of a sloppy history. Dietary history is usually skimped over in the ward rounds and when the dietary history is taken it is not interpreted nor used to help in the management or planning the treatment.
The next line of questioning was “Is your room clean and airy?”. As there is no evidence of respiratory symptoms or even fever this line of questioning seems irrelevant. Her family lived in a one room apartment with a toilet and lean-too kitchen in a crowded part of the city. Granted that you have been asked to look into the patient’s social circumstances but common sense is always permitted. Perhaps more information about previous episodes of loss of consciousness might have been more useful. Also asking if she had any food for breakfast might have helped. More information about the vomiting is more appropriate.
She had been in the hospital for three days before being brought to the examination room as a subject for a clinical examination. The patient had been transfused three units of blood (one a day for three days). The candidate asked about any blood transfusions, received the right answer but failed to pay attention to the patient’s answer and failed to mention it in the presentation. The candidate could not say why the patient had needed the blood transfusions. She had not bled and she had not had hemolysis nor did she have any bleeding tendency like purpura. She had a hemoglobin of 3.6 gm/dl on admission. The anemia was iron deficiency with microcytosis, low MCHC, low serum iron and low transferrin saturation and low serum ferritin.
The patient was not breathless, weighed 42 kg for a height of 5 ft 2 inches. She had a pulse of 102/min. BP of 100/58 mmHg, temperature of 98 F. She was pale, had koilonychia, had no jaundice. There small rubbery mobile lymph nodes in her neck on both sides. The size was 1 to 3 cm. Her JVP was not raised, her thyroid was not enlarged, her joints were normal and she had no rash or edema. She had no cardiomegaly but there was a systolic murmur in the aortic area but it did not radiate to the neck. She had a palpable spleen about 5 cm and it was firm. The liver was not enlarged, there was no ascites. The lungs were clear. There was no evidence of polyneuropathy, nor any change in the motor power or the reflexes.
How are you putting it all together? This means investigations and treatment.
Why is she iron deficient?
- Lack of availability in the diet.
- Hookworm infestation.
- Iron malabsorption. Some foods interfere with iron malabsorption: tannates, phosphates, phytates (mineral-binding compounds found in whole grains and seeds), and foods high in calcium.
- Celiac disease can contribute to anemia by several mechanisms, including iron deficiency, reduced absorption of supplemental iron, and malabsorption of other nutrients required for red blood cell (RBC) production including vitamin B12, folic acid, and copper. Anemia may be the only manifestation.
- Autoimmune gastritis and H. pylori – Gastritis related to an autoimmune mechanism (eg, anti-parietal cell antibodies) or H. pylori has also been implicated in causing iron deficiency.
- Urinary loss of iron. Chronic or intermittent intravascular hemolysis with hemosiderin accumulation in urinary epithelial cells may lead to iron loss through urinary shedding of these cells. Examples include individuals with intensive athletic training, prosthetic heart valve-associated hemolysis, or paroxysmal nocturnal hemoglobinuria (PNH).
- Pulmonary hemosiderosis, such as in individuals with diffuse alveolar hemorrhage or idiopathic pulmonary hemosiderosis may lead to iron loss through swallowing of iron-laden alveolar or bronchial epithelial cells. These conditions also may cause a component of functional iron deficiency, in which iron is trapped in pulmonary macrophages.
- Rare inherited disorders/IRIDAIRIDA due to TMPRSS6 mutation. Iron refractory iron deficiency anemia (IRIDA) is a rare inherited disorder in which absorption of oral iron is markedly impaired. IRIDA is caused by loss-of-function mutations of the TMPRSS6/matriptase 2 gene, which encodes a serine protease that cleaves membrane-bound hemojuvelin.
- Extreme athletics. Iron deficiency may be seen in some athletes, due to gastrointestinal bleeding or reduced iron intake
Where is iron stored in the body?
- Hemoglobin in circulating RBCs – Approximately 2 g, corresponding to approximately 2000 mL (25 to 30 mL/kg) of RBCs
- Iron-containing proteins (eg, myoglobin, cytochromes, catalase) – Approximately 400 mg
- Plasma iron bound to transferrin – 3 to 7 mg
- Storage iron in the form of ferritin or hemosiderin – Approximately 0.8 to 1 g (men); approximately 0.4 to 0.5 g (women)
Ferritin levels are used as a surrogate for iron stores and are generally a good measure of storage iron as long as the individual does not have an active inflammatory process or chronic disease (ferritin is an acute phase reactant). For ferritin levels in the range from 20 to 300 ng/mL, there appears to be a direct quantitative relationship between the ferritin concentration and iron stores.
Stages of iron deficiency.
- iron deficiency but no anemia.
- anemia but it is normocytic and normochromic but with no increase in retic count.
- profound deficiency results in the classical findings of anemia with RBCs that are hypochromic (low mean corpuscular hemoglobin [MCH]) and microcytic (low mean corpuscular volume [MCV]). Reticulocyte production cannot be increased in the setting of iron deficiency, and the reticulocyte count becomes inappropriately low (despite being in the “normal” range in many cases).
Measuring iron deficiency anemia.
- Low levels of ferritin and serum iron (Fe).
- Increased levels of transferrin (Tf; total iron binding capacity [TIBC]). If only transferrin concentrations are available, they can be converted to the TIBC (in mcg/dL) by multiplying the transferrin concentration (in mg/dL) by 1.389.
- Low percent saturation of transferrin (ie, Fe/TIBC or Fe/Tf, stated as a percent).
- Increased unsaturated iron binding capacity (UIBC = TIBC – Fe).
What is this girl likely to have?
- Absolute iron deficiency – Absolute iron deficiency refers to the absence of (or severely reduced) storage iron in the monocyte-macrophage system, including bone marrow, liver, and spleen.
- Functional iron deficiency (also referred to as iron-restricted erythropoiesis) – Some individuals have barely adequate iron stores for normal hematopoiesis, but the iron is not available for RBC production. There are two main categories/mechanisms:
- Anemia of chronic inflammation – The most common mechanism is a block in iron release from macrophages back into the circulation, which occurs in the setting of inflammation and increased hepcidin production (ie, anemia of chronic inflammation, also called anemia of chronic disease [ACD]). Common causes include infections, malignancies, bariatric surgery (in certain individuals), or chronic medical conditions such as diabetes.
What is this patient likely to have?
- Disseminated TB. Despite the lack of pulmonary symptoms it is possible for her to pick up M tuberculosis from an open case in her neighborhood. She is malnourished and so is more then usually vulnerable. Lymph nodes and an enlarged spleen are found in disseminated TB. If an X ray chest shows miliary shadows the diagnosis can be confirmed further.
- Lymphoma affecting her pylorus. GI lymphomas are rare but should be ruled out as she has enlarged lymph nodes and an enlarged spleen.
- The iron deficiency is a confounding factor.
- Malnutrition needs to be addressed and treated. Iron refractoriness will remain until the inflammation subsides.
This patient was investigated and her iron deficiency was confirmed. She had no abnormal cells or blast cells in her blood film. The platelets are normal. The leucocyte count is unremarkable and the reticulocyte was 3%. The X ray was unremarkable with no hilar lymphadenopathy. An ultrasound of the abdomen showed a normal liver, confirmed the enlarged spleen and showed no evidence of any abdominal lymph nodes. A CT of the abdomen showed thickening of wall of the pyloric end of the stomach. A lymph node biopsy showed only reactive changes. It was decided to do an endoscopy and a biopsy was taken from the pyloric end of the stomach where cerebroid thickening of the mucosa was seen. Multiple biopsies were taken from the esophagus and other sites in the stomach and duodenum.
What was the consultant suspecting? The vomiting probably had an adverse effect on the anemia. The vomiting may be mechanical i.e. some obstruction in the area of the pylorus. She is not at the age (60 years) when lymphomas are seen in the stomach and also the wrong gender. Does anybody remember MALT?