Effects of hypochromic microcytic anemia induced by an iron-copper free diet on whole blood filterability and other hemorheological parameters in rats

In this work the author has attempted to gain insight into the significance of iron depletion by the use of 4 simple calculations, justification for which is found in recent articles. These are: (a) iron with which the infant is born; (b) iron retained from the food; (c) iron being used by the tissues and therefore unavailable for hemoglobin, and (d) iron combined with the total mass of hemoglobin. With these 4 figures it is possible to estimate the iron still potentially available for use (the "reserves" or "stones"). When the difference between a + b and c + d has reached about zero, depletion is considered to exist. The following characteristics of depletion may be emphasized: Depletion is the result of gain in weight and maximum possible usage of iron. It is therefore a normal result of growth and need not be associated with anemia. As soon as depletion has occurred, the organism is thereafter dependent on current absorption of iron. This is ordinarily sufficient, even with a diet of milk alone, to maintain an adequate concentration of hemoglobin after about 8 to 10 months of age. Severe anemia due to depletion alone is practically confined to premature babies whose relative gain in weight is rapid. Severe anemia in other than premature babies is the result of a number of factors by which iron becomes unavailable or is actually diverted from hemoglobin to storage. Response to iron medication is considerably better in infants with depletion than in those in whom some factor is present that interferes with iron utilization, and which is not connected by the mere giving of iron. The dependence on current absorption, whether the result of depletion or non-availability, introduces a certain precariousness which is apparently characteristic of this time of life. The organism gets along from day to day if nothing happens, but may not be able to meet an emergency, whether this appears as a rapid gain in weight, or a necessity to repair damage done by severe infection. If we consider iron deficiency as the cause of anemia, we can think of deficiency as due to a number of factors of which depletion is only one. The development and characteristics of depletion have been considered in this paper; other factors in iron deficiency will be considered in subsequent papers.

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Giant adrenal hemangioma: Unusual cause of huge abdominal mass

Canadian Urological Association Journal ◽

10.5489/cuaj.2967 ◽

2015 ◽

Vol 9 (11-12) ◽

pp. 834 ◽

Cited By ~ 3

Author(s):

Mohamed Tarchouli ◽

Adil Boudhas ◽

Moulay Brahim Ratbi ◽

Mohamed Essarghini ◽

Noureddine Njoumi ◽

...

Keyword(s):

Adrenal Gland ◽

Abdominal Mass ◽

Abdominal Distension ◽

Microcytic Anemia ◽

Hypochromic Microcytic Anemia ◽

Normal Limits ◽

Laboratory Examinations ◽

Right Lobe ◽

The Right

Adrenal hemangioma is an extremely rare benign and non-functioning neoplasm of the adrenal gland. We report a case of a 71-year-old woman admitted for intermittent abdominal pain and abdominal distension associated with vomiting and chronic constipation for 5 years. Physical examination revealed a large abdominal mass. Both computed tomography scan and magnetic resonance imaging suggested hemangioma in the right lobe of the liver. Laboratory examinations and tumour markers were within normal limits, except for hypochromic microcytic anemia. The mass was removed intact by conventional surgery and histopathology revealed a cavernous hemangioma of the adrenal gland with no signs of malignancy. Surgical resection was curative, with no recurrence at the 2-year follow-up.

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Abnormal megakaryocytopoiesis in the Belgrade laboratory rat

Blood ◽

10.1182/blood.v77.3.456.456 ◽

1991 ◽

Vol 77 (3) ◽

pp. 456-460 ◽

Cited By ~ 11

Author(s):

Z Rolovic ◽

N Basara ◽

N Stojanovic ◽

N Suvajdzic ◽

V Pavlovic-Kentera

Keyword(s):

Iron Transport ◽

Basic Mechanism ◽

Microcytic Anemia ◽

Severe Anemia ◽

Erythroid Progenitors ◽

Hypochromic Microcytic Anemia ◽

Iron Treatment ◽

Full Correction ◽

Partial Correction ◽

Cell Disorder

Abstract The Belgrade laboratory (b/b) rat has a hereditary hypochromic microcytic anemia because of defective transmembrane iron transport into erythroblasts. The present study was prompted by our previous work in which we showed that the b/b rat has hypomegakaryocytic thrombocytopenia associated with increased megakaryocyte size. To define the basic mechanism underlying this abnormality in the b/b rat we have studied both megakaryocytopoiesis and granulopoiesis in anemic b/b rats, chronically transfused b/b rats, iron-treated b/b rats, and controls. We have found decreased concentrations of megakaryocyte and granulocyte progenitors in the marrow of b/b rats. Full correction of the severe anemia by chronic transfusion resulted in normalization of megakaryocyte progenitors, small acetylcholinesterase positive cells, megakaryocyte size, and platelet counts, along with granulocyte progenitors. In contrast, the partial correction of anemia obtained by iron treatment resulted in improvement, but not normalization, of these parameters. These findings indicate that abnormal megakaryocytopoiesis in the b/b rat can be best interpreted as a consequence of hypoxia because of the severe anemia. Because we have recently shown that the number of erythroid progenitors in b/b rats is also low, we propose that abnormal megakaryocytopoiesis in this animal is a reflection of an acquired stem cell disorder induced by the prolonged hypoxia resulting from the severe anemia.

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Abnormal megakaryocytopoiesis in the Belgrade laboratory rat

Blood ◽

10.1182/blood.v65.1.60.bloodjournal65160 ◽

1985 ◽

Vol 65 (1) ◽

pp. 60-64 ◽

Cited By ~ 1

Author(s):

Z Rolovic ◽

T Jovanovic ◽

Z Stankovic ◽

N Marinkovic

Keyword(s):

Genetic Defect ◽

Cell Lineage ◽

Microcytic Anemia ◽

Severe Anemia ◽

Red Cell ◽

Present Evidence ◽

Hypochromic Microcytic Anemia ◽

Laboratory Rat ◽

Maturation Rate ◽

Normal Rat

The Belgrade laboratory rat (b/b rat) has hereditary, hypochromic, microcytic anemia with a variety of red cell abnormalities. Although this anemic syndrome has been recently ascribed to the defective delivery of iron to the developing red cell, the basic hematopoietic defect is still unknown. In this article we present evidence that the b/b rat has an additional hematologic defect. We have found that the megakaryocyte number in the marrow of the b/b rat is decreased to one half that of the normal rat, but the maturation rate of recognizable megakaryocytes is accelerated and the size is increased. The platelet count is moderately reduced. These findings indicate that megakaryocytopoiesis in the anemic b/b rat is abnormal and suggest that the genetic defect may involve the progenitors of the megakaryocyte cell lineage. Alternatively, the megakaryocytic abnormalities may be secondary to the severe anemia.

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Mutation of the gastric hydrogen-potassium ATPase alpha subunit causes iron-deficiency anemia in mice

Blood ◽

10.1182/blood-2011-04-350082 ◽

2011 ◽

Vol 118 (24) ◽

pp. 6418-6425 ◽

Cited By ~ 17

Author(s):

Lara Krieg ◽

Oren Milstein ◽

Philippe Krebs ◽

Yu Xia ◽

Bruce Beutler ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Osmotic Fragility ◽

Microcytic Anemia ◽

Deficiency Anemia ◽

Α Subunit ◽

Hypochromic Microcytic Anemia ◽

Gastric Proton Pump ◽

Potassium Atpase

Abstract Iron is an essential component of heme and hemoglobin, and therefore restriction of iron availability directly limits erythropoiesis. In the present study, we report a defect in iron absorption that results in iron-deficiency anemia, as revealed by an N-ethyl-N-nitrosourea–induced mouse phenotype called sublytic. Homozygous sublytic mice develop hypochromic microcytic anemia with reduced osmotic fragility of RBCs. The sublytic phenotype stems from impaired gastrointestinal iron absorption caused by a point mutation of the gastric hydrogen-potassium ATPase α subunit encoded by Atp4a, which results in achlorhydria. The anemia of sublytic homozygotes can be corrected by feeding with a high-iron diet or by parenteral injection of iron dextran; rescue can also be achieved by providing acidified drinking water to sublytic homozygotes. These findings establish the necessity of the gastric proton pump for iron absorption and effective erythropoiesis.

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OBSERVATIONS ON THE EFFECT OF MASSIVE DOSES OF IRON GIVEN INTRAVENOUSLY TO PATIENTS WITH HYPOCHROMIC ANEMIA

Blood ◽

10.1182/blood.v1.2.129.129 ◽

1946 ◽

Vol 1 (2) ◽

pp. 129-142 ◽

Cited By ~ 38

Author(s):

ANNE TOMPKINS GOETSCH ◽

CARL V. MOORE ◽

VIRGINIA MINNICH

Keyword(s):

Oral Therapy ◽

Average Rate ◽

Recovery Period ◽

Hypochromic Anemia ◽

Microcytic Anemia ◽

The Body ◽

Therapeutic Procedure ◽

Hypochromic Microcytic Anemia ◽

Iron Administration ◽

Toxic Reactions

Abstract Massive doses of iron (from 0.608 to 1.32 Gm. as colloidal terric hydroxide or colloidal ferric oxide) were given intravenously in single infusions to 8 different patients with hypochromic microcytic anemia. One patient was given a second injection after an interval of four months, so that nine administrations were made. The following observations were made: 1. The reticulocyte response was higher in each instance than would be expected in oral therapy. In 3 additional patients in whom injection had to be discontinued after 0.070, 0.180, and 0.123 Gm. of elemental iron had respectively been given, the reticulocyte rises were higher than were the average responses reported by Heath18 after optimal oral therapy. This at least suggests that "optimal" oral therapy does not provide a maximal stimulus to outpouring of reticulocytes from the bone marrow. Comparable doses of iron given to 3 control subjects with normal hemoglobin levels did not cause a reticulocytosis. 2. The average rate of hemoglobin regeneration per 100 cc. of blood per day was 0.224 Gm.; the lowest value was 0.16 Gm. and the highest 0.27 Gm. These figures were calculated for the rise that occurred from the day of iron administration to the time at which the rate of hemoglobin increase was obviously becoming slower. Since correction was not made for blood loss in 3 of the patients during the period of regeneration, the figures for the rate of hemoglobin formation are lower than they otherwise would have been. Even so they are distinctly greater than those usually obtained following oral therapy (table 2), but no greater than is found in an occasional patient given iron by mouth. The data suggest that the fastest rate of hemoglobin regeneration that can be stimulated by iron in subjects with hypochromic anemia approximates 0.3 Gm. per 100 cc. per day. 3. Calculations indicated that from 71.8 to 99.7 per cent of the injected iron was apparently used for the synthesis of hemoglobin. These figures are likewise lower than they would have been if several of the patients had not lost blood during the recovery period. The observation of other workers that parenterally administered iron is almost completely retained by the body and converted into hemoglobin was therefore confirmed. 4. Toxic reactions to the injected iron are described in detail. They were severe in all but two instances, and in 3 patients were so alarming that injection of iron had to be discontinued. There can be no doubt that the reactions to iron parenterally administered in large doses are great enough to contra-indicate use of this measure as a therapeutic procedure.

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Whole blood filterability and blood oxygen transport in human hypertension

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-1983-3402 ◽

2016 ◽

Vol 3 (4) ◽

pp. 367-373 ◽

Cited By ~ 2

Author(s):

J. Freitas ◽

J. Braz-Nogueira ◽

J. Nogueira da Costa ◽

J. Martins e Silva

Keyword(s):

Oxygen Transport ◽

Whole Blood ◽

Blood Oxygen ◽

Human Hypertension ◽

Blood Filterability

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Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake

Blood ◽

10.1182/blood-2005-04-1550 ◽

2005 ◽

Vol 106 (12) ◽

pp. 3985-3987 ◽

Cited By ~ 31

Author(s):

Monika Priwitzerova ◽

Guangjun Nie ◽

Alex D. Sheftel ◽

Dagmar Pospisilova ◽

Vladimir Divoky ◽

...

Keyword(s):

Protein Expression ◽

Iron Uptake ◽

Chinese Hamster ◽

Microcytic Anemia ◽

Homozygous Mutation ◽

Divalent Metal Transporter 1 ◽

Divalent Metal Transporter ◽

Hypochromic Microcytic Anemia ◽

Functional Consequences ◽

Uptake Activity

We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G > C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expression and function. In contrast, deletion of exon 12 led to a decreased expression of the protein and disruption of its subcellular localization and iron uptake activity. We hypothesize that the residual protein in hematopoietic cells represents the functional E399D DMT1 variant, but because of its quantitative reduction, the iron uptake activity of DMT1 in the patient's erythroid cells is severely suppressed.

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Rational diagnostic work-up of anemia

LaboratoriumsMedizin ◽

10.1515/labmed-2016-0017 ◽

2016 ◽

Vol 39 (5) ◽

Author(s):

Jan Hastka ◽

Georgia Metzgeroth

Keyword(s):

Macrocytic Anemia ◽

Hemoglobin Concentration ◽

Epidemiological Data ◽

Microcytic Anemia ◽

Differential Diagnoses ◽

Deficiency Anemia ◽

Anemia Of Chronic Disease ◽

Hypochromic Microcytic Anemia ◽

Diagnostic Role ◽

The Individual

AbstractAnemia is defined as a decrease in the hemoglobin concentration below the age- and sex-specific lower limit, established by WHO as 130 g/L in men and 120 g/L in women. In principle, there are many differential diagnoses which must be considered. The diagnostic evaluation furthermore is complicated by the fact that anemias are often multicausal. A rational evaluation of anemia should always take into account the epidemiological data and also the individual patient’s history. The classification according to the size and the hemoglobin content of the red blood cells based on the erythrocyte indices still plays a central diagnostic role. The worldwide most important cause of a hypochromic-microcytic anemia is iron deficiency. Anemia of chronic disease (ACD) and thalassemia are to be considered as differential diagnoses. Disorders of vitamin B12 and folic acid metabolism are clinically the most important causes of hyperchromic-macrocytic anemia. The normochromic-normocytic group includes most forms of anemias. In these cases one should not try to cover all possible causes by a fully comprehensive laboratory panel within the first blood sample already. It is more appropriate to proceed step-by-step to evaluate the most frequent and clinically most important reasons first. This especially applies to geriatric and multimorbid patients where the diagnostic effort must be adjusted to the individual needs and prognosis of the patient, not only from economical but also from ethical reasons. In unexplained anemias, consultation of a hematologist should be considered. In case of doubt, bone marrow biopsy is required to precisely evaluate the hematopoiesis and to exclude a hematological disorder.

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Two nonsense mutations in the TMPRSS6 gene in a patient with microcytic anemia and iron deficiency

Blood ◽

10.1182/blood-2008-05-154740 ◽

2008 ◽

Vol 112 (5) ◽

pp. 2089-2091 ◽

Cited By ~ 79

Author(s):

Flavia Guillem ◽

Sarah Lawson ◽

Caroline Kannengiesser ◽

Mark Westerman ◽

Carole Beaumont ◽

...

Keyword(s):

Iron Deficiency ◽

Microcytic Anemia ◽

Deficiency Anemia ◽

Nonsense Mutations ◽

Hepcidin Expression ◽

Hypochromic Microcytic Anemia ◽

Iv Iron ◽

Membrane Bound ◽

Inherited Mutations ◽

Iron Utilization

Abstract Genetic causes of hypochromic microcytic anemia include thalassemias and some rare inherited diseases such as DMT1 deficiency. Here, we show that iron deficiency anemia with poor intestinal absorption and defective iron utilization of IV iron is caused by inherited mutations in TMPRSS6, a liver-expressed gene that encodes a membrane-bound serine protease of previously unknown role that was recently reported to be a regulator of hepcidin expression.

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