FACTS ON FINGER TIPS

   2. IRON DEFICIENCY ANAEMIA                                                                  

     Salient Features

  Definition

1. Hypochromic microcytic anaemia, with a haemoglobin < 12.5g/dl in men and <11.5g/dl in women. Mean corpuscular volume is <76fl, and mean corpuscular haemoglobln  concentration <32g/dl

 Epidemiology

1. All ages may be affected
2. Iron deficiency anaemia is common in menstruating women- it is estimated that 15 percent are affected

 Aetiology

1. Chronic bleeding, menorrhagia or gastrointestinal blood loss, such as oesophagitis, peptic ulcer, disease, carcinoma, and inflammatory bowel disease
2. Poor diet, particularly in the elderly and the poor.
3. Restricted diets such as vegetarians
4. Malabsorption, such as in coeliac disease

 Presentation

1. Symptoms of chronic iron deficiency include tiredness, weakness, and shortness of breath
2. Tachycardia may present in severe anaemia
3. Clinical signs and symptoms are unreliable and laboratory diagnosis is essential

 Investigations

1. Serum ferritin, iron, and total iron binding capacity
2. Consider checking for faecal occult blood
3. Urine dip stick testing

 Management

1. Detailed dietary and menstrual history
2. Patients over 40 my need upper and/or lower GI endoscopy to exclude an underlying Gi malignancy
3. Iron supplementation two or three times daily
4. Patients unable to tolerate iron therapy may need intramuscular iron

 Key Points

1. Taking iron after food may reduce GI side effects
2. Continue treatment for three months after the haemoglobin has returned to normal
3. Refer patients with persistent refractory anaemia

8. DISORDERS AND /OR ADVERSE REACTIONS - Nutrition- SUMMARY

Ref - Other information

Contents-

1.Evidence Based Medicine

2.Facts on Finger Tips                                                                                                            i.Foliate Deficiency                                                                                                              ii. Iron Deficiency  Anaemia 

3.Disorders and/or Adverse Reactions                                                                               Items 1 to 14         

FACTS ON FINGER TIPS

 1. FOLIATE DEFICIENCY                                                                   

     Salient Features

  Definition

1. Macrocytic anaemia with an MCV greater than 96fl due to an underlying foliate deficiency

 Aetiology

1. Inadequate dietary intake is often due to poor diet
2. Malabsorption, for example in alcoholics
3. Increased demand, such as during pregnancy
4. Drugs such as anticonvulsants

 Clinical features

1. Inadequate digestion is common in the elderly, the socially deprived, alcoholics and people with anorexia
2. Take a careful drug history
3. Malabsorption states such as Crohn’s disease and post- gastrectomy need to be kept in mind
4. Tiredness and shortness of breath

 Investigations

1. FBC -both show megaloblastic anaemia

 Management

1. Treat the underlying condition
2. Exclude a coexistent vitamin B12 deficiency before starting treatment with folic acid
3. Dietary advice to increase foliate-rich foods including green leafy vegetables, yeast, liver, mushrooms and nuts
4. Supplementary folic acid. Usual dose is 5mg once daily for four months
5. Pregnant women should take folic acid before conception and up to 12 weeks gestation to prevent neutral tube defects

 
8. DISORDERS AND /OR ADVERSE REACTIONS - NUTRITION - SUMMARY

( Ref- Harrisons - Priniciples of Internal Medicine Ninth Edition )

1. Thrombocytopenia  ( 1555 )
2. Aplastic anemia  (Pancytopenia)- (1525)
3. Agranulocytosis ( Schultz syndrome)- ( 287 )
4. Megaloblastic anemia (1518)
5. Hemolytic anemia (270)
6. Hemolytic anemia ( in G6PD deficiency ) (1545)
7. Lyphadenopathy ( 280 )
8. Leukocytosis ( 387 )
9. Eosinophilia ( 290 )
10. Iron -Deficiency Anemia (1515)
11.Sideroblastic Anemias (1517)
12. Pernicious Anemia (1521)
13. Folic Acid Deficiency (1522)
14.Sickle- Cell Anemia (1547)

1.Thrombocytopenia -(1555)

The normal platelet count ranges from 150,000 to 400,000 per cubic millimeter. A platelet count of  less than 100,000 per cubic millimeter is generally considered to constitute thrombocytopenia.
There is an apparent relationship between the platelet count , fever, and the severity of bleeding. A sudden drop in the platelet count,  fever, and anemia aggravate the hemostatic defect of thrombocytopenia. With platelet count above 40,000 per cubic millimeter , bleeding may occur  after injury or surgery but spontaneous bleeding is uncommon.

      Adverse reaction - drugs
       1. Quinidine
       2. Quinine
       3. Furosemide
       4. Chlorthalidone
       5. Thiazides
       6. Gold salts
       7. Cotrimoxazole
       8. Aspirin
       9. Indomethicin
       10. Phenylbutazone
       11. Oxyphenbutazone
       12. Acetazolamide
       13. Phenytoin and other hydantoins
       14. Methyldopa
       15. Carbamazepine
       16. Digtoxin
       17. Novobiocin

2. Aplastic anemia (Pancytopenia) -(1525)
 
The term aplastic anemia was applied to all patients with refractory and progressive pancytopenia until advent of bone marrow examination for diagnostic purposes. Since then it has become apparent  that a variety of pathological processes can lead to pancytopenia . By convention the aplastic anemia, should be reserved  for patients who have a fatty or - empty - bone marrow due to severe  hypoplasia  of the erythroid, myeloid and thrombopoetic cell lines.

     Adverse reaction - drugs ( 387 )
      1. Chloramphenicol
      2. Phenytoin
      3. Mephenytoin
      4. Trimethsdione
      5. Phenylbutazone
      6. Oxyphenbutazone
      7. Gold salts
      8. Mepacrine
      9. Quinacrine
      10. Potassium perclorate
      11. Cytotoxics

3. Agranulocytosis (Schultz Syndrome)- ( 287 )

Agranulocytosis (or Schultz  syndrome ) - severe neutropenia occurs as an occassional or rare reaction of a great variety of drugs. In most cases the patient is seen by the physician several weeks or months after the offending agent and presents acutely ill with fever, sore throat, and oral  or parianal ulceration.The total leukocyte count is often 1000 to 2000 per cubic millimeter  and neutrophils are absent from the blood  and bone marrow. Marrow examination generally exclude
leukemia as the cause.

With some drugs eg chloramphenicol, phenothiazines, carbamazepine (Tergretol ) and
propylthiouracil, patients may have a gradual declining neutrophil count, probably due to suppressed neotrophil production.  It is not certain these patients will develop agranulocytosis if the drug is discontinued. However, as a rule, the presumed offending drug should be discontinued if the neutrophil count falls below 3000 per cubic millimeter 
 
     Adverse reaction - drugs ( 387 )
      1. Chloramphenicol
      2. Sulphonamides
      3. Phenylbutazone
      4. Oxyphenabutazone
      5. Gold salts
      6. Indomethicin
      7. Propylthiouracil
      8. Methimazole
      9. Carbimazole
      10. Phenothiazines
      11. Cytotoxics
      12. Tolbutamide
      13. Cotrimoxazole
      14. Tricyclic antidepressants

4. Megaloblastic anemia (1518)
 
The  megaloblastic anemias are important examples of disorders erythroid maturation with distinctive blood and bone marrow morphology. These disorders are characterized by impairment of deoxyriboneuclic acid (DNA ) sythesis. Cells primarily affected  include those having a relatively rapid turnover such as hematopoietic precursors in the bone marrow and the mucosal epithelium of the gastrointestinal tract. Although cell division is sluggish, cytoplasmic development progresses normally. Thus megaloblastic cells tend to be large, with an increased ratio of ribonucleic acid (RNA)
to DNA.

Megaloblastic cells tend to be destroyed in the bone marrow in excessive numbers, an abnormalilty termed -ineffective erythropoiesis-. In a severely megaloblastic patient as many as 90% of the red blood cell precursors may be destroyed before they are released into the blood stream, compared with 10 to 15% in the normal subject.

Most megaloblastic anemias are due to deficiency of vitamin B12 and/or folic acid

      Adverse reaction - drugs (387 )
        1.Folate antagonists
        2. Cotrimozole
        3. Phenytoin
        4. Primidone
        5. Phenobarbital
        6. Triamterene
        7. Trimethoprim
        8. Oral contraceptives

5. Hemolytic anemia (270)
 
Hemolytic anemia are encountered  much less frequently than the anemias due to decreased  red cell production, Although they are a diverse group , the hemolytic anemias have a number of clinical features in common. Patients with hemolytic anemia generally have a brisk reticulocytosis

The bone marrow predictably reveals erythroid hyperplasia. A bone marrow examination is generally not indicated in  the evaluation of a patient with hemolytic anemia, unless as associated disorder such as lymphoma is suspected.

      Adverse reaction - drugs ( 387 )
        1.  Methyldopa
        2. Levodopa
        3. Mefanamic acid
        4. Melphalan
        5. Isoniazid
        6. Rifampicin
        7. Sulfonamides
        8. Penicillins
        9. Cephalosporins
        10. Insulin
        11. Quinidine
        12. Chlorpromazine
        13. Phenacetin
        14. p-Aminosalicylic acid
        15. Dapsone

6. Hemolytic anemia ( in G6PD deficiency )- (1544)

The normal red blood cells is well endowed to protect itself against oxidant stress. Upon
exposure to an offending drug or toxin, the amonut of glucose that is metabolised via the
hexose-monophosphate shunt is increaesed severalfold. In this way reduced glutothione
is regenerated , proteceting the sulfhydryl groups of hemoglobin and perhaps the red cell
membrane from oxidation.

Individuals with inherited defect in the hexose-monophosphate shunt are unable to maintain  an adequate level of reduced glutathione in their blood cells.  As a result , hemoglobin sulfhydryl groups become oxidized and the hemoglobin tends to precipitate within the red blood cells forming  Heinz bodies. Among the congenital defects by the most common id G6PD deficiency
   
      Adverse reaction - drugs
        1. Antimalarials eg primaquine
        2. Chloramphenicol
        3. Dapsone
        4. Nalidixic acid
        5. Nitrofurantoin
        6. Sulfonamides
        7. Aspirin
        8. Phenacetin
        9. p-Aminosalicylic acid
        10. Quinidine
        11. Vitamin C
        12. Vitamin K
        13. Cotrimozole
        14. Probenecid
        15. Procainamide
       
7. Lyphadenopathy ( 280 )
     
In normal persons nodes are not palpable or barely palpable.
Lymphadenopathy reflects significant disease more often in adults than in children. however, palpable nodes do not always connote serious disease. They may reflect merely minor  trauma to and infections of the structure being drained, such as the hands of a manual laborer, the upper extremities ( axillary ) , upper respiratory tract and teeth and most frequently ,the lower extremites.
 
       Adverse reaction - drugs ( 387 )
         1. Phenytoin
          2.Primidone

8. Leukocytosis ( 387 )

Patients with extreme thrombocytosis or, more rarely, extreme leukocytosis may demonstrate the phenomenon of pseudohyperkalemia. Platelets or white cells release potassium during clotting in vitro. When serum potassium may be grossly abnormal, plasma potassium is not increased.

Artificial elevation of plasma  potassium may occur if blood is drawn after repeated fist clenching to make veins prominent during application of a tourniquet.

Artificial hyperkalemia may be suspected when electrocardiographic abnormalities are absent despite elevation of serum potassium.
 
      Adverse reaction - drugs
        1. Lithium
        2. Corticosteroids

9. Eosinophilia ( 290 )

More than 500 eosinophils per cubic milimeter of blood is infrequent in normal individuals. The most common cause for mild eosinophilia in hospitalized patients is probably some form of drug allergy. Parasitic infections, principally helminitic infections cause eosinophilia, especially in the invasive phase. In these diseases the eosinophil count is rarely greater than 25,000 per cubic with the highest counts probably occurring in trichonosis.

The hypereosinophililic syndrome cause the highest eosinophil counts, occassionally in the range of 50,000  to 100,000 per cubic millimeter or higher. Many tissues become infiltrated by eosinophilis,  a condition  leading to organ dysfunction, paticularly heart failure.   

      Adverse reaction - drugs ( 387 )
         1. Erythromycin estolate
         2. Sulfonamides
         3. Chlorpropamide
         4. p-Aminosalicylic acid
         5. Imiprimine
         6. Nitrofurantoin
         7. Procarbazine
         8. Methotrexate
 
10. Iron -Deficiency Anemia (1515)

Children, female adolescents, and women in their reproductive years are most in danger of developing iron deficiency. However, any circumstance which lead to increased demand on the iron stores of the body can result in iron deficiency. The possible factors leading to iron deficiency
are-
1. insufficient iron in the diet 2. impaired absorption 3. increased requirements and 4. loss of blood. In many instances, more than one of these factors is responsible for the resulting deficiency 

11.Sideroblastic Anemias (1517)

These anemias are a group of heterogenous disorders in which a population of circulating hypochromic , microcytic erythrocytes is found in the blood, and  -ringed- sideroblasts are present in the bone marrow. Sideroblasts are red blood cell precursors containing nonheme iron granules than stain with Prussian blue.

In normal subjects, one out of three small , blue granules may be seen in 30 to 50 percent of normoblasts. In patients with sideroblastic anemias, both the size and number of these iron-containing granules are increased and the granules tend to form a ring around the
nucleus. 

12. Pernicious Anemia (1521)

The most common cause of Vitamin B12 deficiency in temperate climates is pernicious anemia, in which intrinsic factor secretion ceases owing to atrophy of the gastric mucosa. It is seen mostly seen in Northern European  descent and much less common in Southern European , blacks, and Orientals. Men and women are equally affected. It is a disease of the elderly, the average patient  presenting near age 60;  it is rare under 30 although typical pernicilous anemia can be seen in children under 10 ( juvenile pernicious anemia)

An inherited condition in which an abnormal intrinsic factor is secreted by histologically normal stomach will cause Vitamin B12 deficiency, which appears in infancy or early childhood

13. Folic Acid Deficiency (1522)

Patients with  folic deficiency are more apt to be malnourished than those with vitamin B12 deficiency. Accordingly, they are likely to appear wasted rather than flabby. The gastrointestinal manifestations are similar to but may be more widespread  and more severe than those of pernicious anemia.

Diarrhea is often present and cheilosis and glossitis are also encountered. However, neurological abnormalities  like those seen in pernicious anemia do not occur.

14.Sickle- Cell Anemia (1547)

Sickle-cell anemia is the most prevalent form of congenital hemolytic anemia. About 0.15% of black children in the United States have the disease. The incidence is lower among adults because patients with sickle cell anemia have a decreased life expectancy. The protean clinical manifestations of this disorder can be attributed to a specific molecular lesion, the substitution of valine for glutamic acid at the sixth residue of the Beta chain.