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Anemias

- The document discusses red blood cells (erythrocytes), their role in oxygen transport, and the process of erythropoiesis where they are produced in the bone marrow. - Erythropoiesis is regulated by the hormone erythropoietin which stimulates stem cells to mature into red blood cells. Key micronutrients involved in this process are iron, vitamin B12, and folate. Deficiencies in these "haematinics" can lead to megaloblastic or microcytic anemia. - Iron deficiency is particularly common and results in microcytic hypochromic red blood cells. The normal iron cycle is described which involves iron absorption in

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Dr. Suhail S. Kishawi Consultant in Endocrinology and DiabetesConsultant in Endocrinology and Diabetes ‫دد‬‫د‬‫د‬‫د‬‫د‬‫دد‬‫د‬‫د‬‫د‬‫دد‬‫د‬‫د‬‫د‬‫د‬‫د‬‫د‬‫د‬‫د‬ ‫ييييييي‬ ‫يييييي‬ ‫ييييي‬ ‫ييييييي‬ ‫يييييييي‬ ‫ييييييي‬ ‫ييييييي‬ Anemias
The Blood Plasma Red blood cell White blood cell Platelets
Red Blood Cells Contain haemoglobin, a molecule specially designed to hold oxygen and carry it to cells that need it. Can change shape to an amazing extent, without breaking, as it squeezes single file through the capillaries. A biconcave disc that is round and flat without a nucleus
White Blood Cells There are many different types and all contain a big nucleus. The two main ones are the lymphocytes and the macrophages. Some lymphocytes fight disease by making antibodies to destroy invaders by dissolving them. Other lymphocytes make antitoxins to break down poisons. Macrophages ‘eat’ and digest micro-organisms .
Platelets Platelets are bits of cell broken off larger cells. Platelets produce tiny fibrinogen fibres to form a net. This net traps other blood cells to form a blood clot.
Plasma A straw- coloured liquid that carries the cells and the platelets which help blood clot. • Carbon dioxide • Glucose • Amino acids • Proteins • Minerals • Vitamins • Hormones • Waste materials like urea. It also contains useful things like;
| Introduction   Anaemia can be defined as a reduction in the haemoglobin in the blood below normal range for age and sex. Essentially, anaemia is defined as haemoglobin (Hb) concentration: For adult males < 13.5 g/dl For adult women < 11.5 g/dl Anaemia is a global public health problem affecting both developing and developed countries. It has major consequences for human health as well as social and economic development. In 2008, iron deficiency anaemia was considered to be among the most important contributing factors to the global burden of disease. Image above: scanning electron microscope image of red blood cells. Image left: Global WHO map of anaemia in preschool age children.
| The Erythrocyte: An Overview Image: scanning electron microscope of red blood cell To achieve these functions the red cell has several unique properties…. Strength: it has a strong but flexible membrane able to withstand the recurrent shear forces involved in the circulation of blood. Flexibility: the red cell is 7.8 µm across and 1.7 µm thick and yet it is able to fit through capillaries of only 5 µm diameter. This is in-part due to the flexible membrane and shedding of the nucleus. Biconcave shape: increases surface area available for gaseous exchange. Haemoglobin content: unique to the red cell, it is this metaloproteinmetaloprotein molecule which is pivotal in red cell development and Oxygen transport due to its affinity for O2. Function   The primary function of the erythrocyte is the carriage of oxygen from the lungs to the tissues and CO2 from the tissues to the lungs.  The red cell also plays an important role in pH buffering of the blood. Lifespan: Because the fully developed red blood cell has no nucleus the cell cannot divide or repair itself. The lifespan is therefore relatively short (120 days).
Kidney Bone marrow Red blood cells in circulationerythropoietin Stem cells Erythroid precursors An erythrocyte is a fully developed, mature red blood cell. The adult human makes approximately 1012 new erythrocytes every day by the process of erythropoiesis. This is a complex process that occurs within the bone marrow. Before an erythrocyte arrives fully functioning into the blood stream it must develop from a stem cell through an important number of stages As with much human physiology, this system works via a feedback mechanism. 4. There is no store of EPO. The production of erythropoietin is triggered by tissue hypoxia (oxygen tension sensed within the tubules of the kidney) and stops when oxygen levels are normal. | Erythropoiesis 2. EPO stimulates stem cells within the bone marrow which differentiate into erythroid precursors. 3. EPO continues to stimulate primitive erythroid cells (red blood cells) in the bone marrow and induce maturation. 1: Erythropoietin (EPO), a growth factor, is synthesized primarily (90%) from peritubular cells of the kidneys (renal cortex). Macrophages surround and supply iron to these erythroprogenitor cells that become erythroblastic islands.
| Production of erythrocyts :Erythropoiesis
| Erythropoiesis Keypoint! In chronic states of anaemia the opposite may occur. The chronic hypoxic state increases production of EPO. This leads to an increase in the proportion of erythroblasts, expansion and eventually fatty deposition within the bone marrow. During childhood when the growth plates are still present, this expansion can lead to bone deformities such as frontal bossing. This is seen in chronic haemolysis such as thalassaemia. Keypoint! Chronic renal disease / bilateral nephrectomy will reduce or stop the production of EPO. It’s absence or reduction causes anaemia through reduced red cell production. Anaemia due to EPO deficiency will be normocytic in morphology; i.e. the red cell will be a normal shape and size but reduced in number. Hypoxia is the major stimulant for increased EPO production Kidney Bone marrow erythropoietin Erythroid precursors Stem cells Kidney Bone marrow erythropoietin Erythroid precursors Stem cells
|Red cell precursors and the sequence of erythropoiesis Anaemia of chronic disease. In individuals living with a chronic disease (e.g. rheumatoid arthritis),a complex interaction of inflammatory cytokines interferes with the red cell lifecycle by impairing iron metabolism and inhibiting red cell precursors. The end result is a normocytic anaemia. Reticulocytes are an important cell in haematology as they increase in number following a haemorrhage, haemolytic anaemia or from treatment of a haematinic deficiency. They provide an excellent measure of red cell production and the age of the red cell population. In normal blood there is usually about 1 reticulocyte : 100 erythrocytes. Key point! Keypoint! marrow 3.5 Erythrocyte: after 1 week the mature erythrocyte emerges with no organelles and high haemoglobin content.Sequence: amplification and maturation of the erythrocyte Pronormoblast: This is the earliest and largest cell with a large nucleus and no haemoglobin. 3.4. Reticulocytes: Considered the “teenagers” of the the life cycle! This is the FINAL stage of developmentThis is the FINAL stage of development before full maturation.before full maturation. These cells are now anucleate and contain roughly 25% of the final haemoglobin total. They reside mostly in the marrow but in healthy individuals a small number can be found in the peripheral blood. They contain some cell organelles. Normoblasts: these cells go through a large number of progressive changes. Fundamentally they reduce in cell size but increase the haemoglobin concentration in the cytoplasm. The nucleus proportionally decreases until it is extruded before the cell is released in to the blood. blood
|Haematinics Vitamin B12 (cobalamin) and folate (pteroylglutamic acid): These are key building blocks for DNA synthesis and essential for cell mitosis. DNA synthesis is reduced in all cells that are deficient in either folate or vitamin B12. The bone marrow is the factory for blood cell production. In haematinic deficiency, DNA replication is limited and hence the number of possible cell divisions is reduced leading to larger red cells being discharged into the blood i.e. less DNA, less divisions and larger cells. This leads to enlarged, misshapen cells or megaloblasts in the marrow and macrocytic red cells in the blood. •So what exactly are the haematinics? These are the key micronutrients that must be present if a red blood cell and its haemogoblin are to develop in a normal fashion. • These major micronutrients, provided in a balanced diet, are iron, vitamin B12 and folate • A deficiency in any one of these micronutrients can result in anaemia through impaired red cell production within the bone marrow • Assessing haematinic status is key to the investigation of the cause of anaemia Iron: At the centre of the haem molecule is an atom of iron which binds oxygen in a reversible manner. Haemoglobin concentration in the developing red cell is a rate limiting step for erythropoiesis. In iron deficiency, red cells undergo more divisions than normal and, as a result, are smaller (microcytic) and have a reduced haemoglobin content (hypochromic). Iron deficiency is the leading cause of anaemia worldwide. Erthropoiesis is also regulated by the availability of haematinics “Check the haematinics” this is a phrase used frequently on the hospital ward!
|Haematinics in haemoglobin Iron Protoporphyrin GlobinHaem Haemoglobin Thalassaemia • Iron deficiency • Chronic inflammation • Malignancy Chronic infections and inflammatory disorders cause chronic anaemia as a result of; 1. Slightly shortened red blood cell life span 2. Sequestration of iron in inflammatory cells called macrophages Both procedures result in A decrease in the amount Of iron available to make Red blood cells.
|Haematinics: the normal iron cycle Iron deficiency can be identified best by assessing the appearances of the red cells on a blood film. Iron indices in a blood sample are helpful to confirm a lack of iron. In order to interpret these indices, it is vital to understand how the body handles iron ….. Erythroid bone marrow (normoblasts) Reticuloendothelial system; Spleen & macrophages Duodenum Serum transferrin Fe Red blood cells Liver Iron is a key constituent of haemoglobin (60-70% of total body iron is stored here) and it’s availability is essential for erythropoiesis. In iron deficiency, there are more divisions of red cells during erythropoiesis than normal. As a result the red cells are smaller (microcytic) and have a reduced haemoglobin content (hypochromic). 2. Iron is then attached to a protein, transferrin in the serum (plasma), where it is transported to the bone marrow for haemoglobin synthesis. 1. Iron is absorbed from the small intestine in the ferrous state (Fe2+ ; approx. 1mg/day). 3. Dying red cells are recycled by macrophages in the spleen and iron is recycled into the plasma for further use. Soluble transferrin receptors, sTfR are on the red cell surface. These can be measured and are increased in iron deficiency. An iron deficiency profile. Serum Iron: Reduced Serum total iron- binding capacity (TIBC): Increased- the body works hard to bind free iron. Serum ferritin: Reduced-since iron stores are low Serum soluble transferrin receptors: Increased-since red cells attempt to absorb more iron. In iron deficient states, bone marrow iron is reduced. Some iron binds to apoferritin to form ferritin, a storage compound.
Fe+2 Fe+2 Fe+2Fe+2 Dissociation Passive diffusion Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Gut Lumen Mucosal Cell Blood Ferritin Iron salts Fe+3 Free Radical Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+3 Free Radical Transferrin Incorporation into Hb
There are a number of key steps in the absorption of Vitamin B12. The two key locations are the stomach and the terminal ilium. Dietary vitamin B12 binds with intrinsic factor (IF) in the stomach, a transport protein produced by gastric parietal cells. The B12-IF complex then travels through the small intestine and is absorbed by special receptors in the distal ileum. This pathway is important when considering possible causes of Vitamin B12 deficiency. Vitamin B12 deficiency can take up to two years to develop as the body has sufficient stores for this period. Distal ileum Site of B12 absorption Oesophagus Stomach IF Intrinsic factor Vitamin B12 ingested |Haematinics: vitamin B12 Pernicious anaemia: the leading cause of B12 deficiency. IgG autoantibodies target gastric parietal cells and its product IF causing an atrophic gastritis. This results in reduced secretion of intrinsic factor and therefore reduced B12-IF complex for absorption in the distal ileum. Causes of vitamin B12 deficiency 1.Pernicious anaemia 2.Inadequate intake 3.Poor absorption
• Gives red blood cells their colour • Can carry up to 4 molecules of O2 • Associates and dissociates with O2 • Contains iron |Haemoglobin
Hemoglobin (Hb)
When there is a high concentration of oxygen e.g in the alveoli haemoglobin combines with oxygen to form oxyhaemoglobin. When the blood reaches the tissue which have a low concentration of oxygen the haemoglobin dissociates with the oxygen and the oxygen is released into body tissues Function of Haemoglobin
| Haemoglobin and O2 transport A key function of a red cell is to carry and deliver oxygen to the tissues and return CO2 from the tissues to the lungs. As a result the red cell has developed a specialised molecule called haemoglobin (Hb). It is important to gain a basic understanding of its synthesis, functioning and metabolism as errors in these processes lead to a number of anaemic states. It’s waste products are also released when a red cell is destroyed prematurely and are therefore a valuable indicator of haemolysis.   2,3-DPG oxyhaemoglobin deoxyhaemoglobin A molecule called 2,3 –  Diphosphoglycerate  (2,3-DPG) sits between  the β chains and when  increased helps to  offload oxygen to the  tissues. HAEM MOLECULE Each individual globin combines with one haem molecule. This molecule contains iron and binds oxygen in a reversible manner. A mature red cell. GLOBIN CHAIN A normal adult haemoglobin  (Hb A) molecule consists of 4 polypeptide (globin) chains:  α1α2 β1β2. Haemoglobinopathies Thalassaemia: reduced rate of synthesis of either α or β globin chains. Within this group of inherited conditions there may be both ineffective erythropoiesis and haemolysis resulting in a microcytic anaemia sometime also with hypochromia. Sickle cell disease: an inheritance of two abnormal β-globin genes (HbSS). The abnormality consists of a point mutation in the β globin gene. This results in Hb insolubility in it’s deoxygenated state with crystallization within the red cell causing sickling of the cell and vascular occlusion. A common problem that affects primarily the Afro-Caribbean populations. Keypoint! Oxygen (O2)
|Ageing and death Haemolytic anaemias; This is an important group of anaemias. There are many important causes of premature red cell death resulting in anaemia and the increased products of haemolysis within the blood circulation and beyond. Haemolysis: any process that shortens the red blood cell lifespan to less than 120 days. A red cell shows signs of deterioration from around 100 days of the cell’s cycle. Without any DNA or ribosomes, the cell is unable to generate new enzymes (like pyruvate kinase or G6PD that we have been introduced to). These ageing cells are eventually identified by the reticuloendothelial system. This is a system of white blood cells that are present within the spleen, liver and lymph nodes whose main role is to phagocytose damaged or ageing cells. The tired red cells are removed and recycled by macrophages in the spleen and liver. Normally red cell degradation and recycling is managed by the reticuloendothelial system on a daily basis without any problems. When a pathological process causes premature lysis of the red cells, the ability of the body to clear the increased number of waste products may be overloaded.
Haemoglobin Haem Unconjugated bilirubin Conjugated in the liver to the diglucuronide, water- soluble form that is secreted in the bile and then converted to stercobilinogen. Liver Some stercobilin and stercobilogen are reabsorbed from the intestine and excreted in the urine as urobilin and urobilinogen. Raised levels in the urine may indicate haemolysis. 3. Bilirubin Heamolysis results in excess bilirubin causing jaundice (typically lemon yellow colour ) and pigment gallstones. GlobinIron Attaches to transferrin F Is metabolized to amino acids Red blood cell Investigating haemolysis 1.Lactic acid dehydrogenase (LDH) 2.Reticulocyte count 3.Bilirubin 1. LDH is a nucleic enzyme which is released on red cell destruction. The concentration of LDH is measurable from a blood sample and provides an indicator of haemolysis. 3. LDH 2. Reticulocyte count will be elevated in response to the feedback loop during anaemia. The bone marrow increases red cell production. Reticulocytes are larger than mature red blood cells causing a rise in mean cell volume ( MCV). Flow diagram: products of red cell destruction. The protoporphyrin of haem is metabolised to the yellow pigment bilirubin, which is bound to albumin in the plasma. Stercobilinogen is excreted in the faeces Haptoglobins these proteins bind to any free haemoglobin. These proteins can become saturated in a haemolytic anaemia. Haemoglobin can then pass into the urine causing haemoglobinuria or converted to haemosiderinuria.
A red blood cell has an average lifespan of 80 days Erythropoietin (EPO) production is reduced in chronic hypoxic states Iron is transported in the blood bound to apoferritin. A low pH, a high CO2 concentration in the blood and a high number of 2,3-DPG would shift the oxygen dissociation curve to the left Vitamin B12 is absorbed in the jejunum Folate and vitamin B12 are key building blocks of haemoglobin Chronic anaemia and malignancy prevent haem production A deficiency in folate causes a macrocytic megaloblastic anaemia Adult haemoglobin is composed of 2 alpha and 2 beta chains Increased reticulocytes is a key feature of a haemolytic anaemia true / false False! A red blood cell has an average lifespan of 120 days. This is short compared to other blood cells due to the cell having no nucleus or organelles and is thus unable to replace key enzymes and maintain cell function. False! In chronic hypoxic states there is an increased production of EPO. This leads to an increase in the proportion of erythroblasts, expansion and eventually fatty deposition within the bone marrow. True! JAK 2 is a receptor for erythropoietin. A point mutation (tyrosine kinase) in this receptor is implicated in the oncogenisis of several myeloproliferative neoplasm. (90% of Polycythemia vera patients). False! It would shift to the right. All these factors would cause haemoglobin (Hb) to have a reduced affinity for O2 and increase O2 release fom Hb. False! Vitamin B12 binds to intrinsic factor in the stomach, travels through the small bowel and the complex is absorbed in the distal ileum. False! Vitamin B12 and folate are key building blocks of DNA. True! Chronic anaemia and malignancy block iron from being incorporated into the haem molecule. True! Both folate and vitamin B12 are key micronutrients for DNA synthesis. Deficiencies cause a macrocytic megaloblastic anaemia. True! The normal adult Hb contain 4 globin chains (often notated as α2β2). True! The cells will be elevated in response to our feedback loop during anaemia. With excessive destruction of red cells, the bone marrow increases production.
| Defining anaemia | Dehydration | Reduced plasma volume may  mask anaemia. | Pregnancy or splenomegaly | These can produce an increase in  plasma volume reducing the  apparent haemoglobin  concentration even though  circulating haemoglobin levels are  normal.   | Acute significant blood loss | Following acute blood loss it may  take up to a day for the plasma  volume to be replaced and  anaemia to present. Therefore,  clinical features of shock and  reduced blood volume may occur  before a fall in haemoglobin  concentration.
|Clinical features of anemia 1. The cardiovascular system Cardiac compensation is the major adaptation. Both stroke volume and heart rate increase mobilizing greater volumes of oxygenated blood to the tissues. This can present with palpitations, tachycardia and heart murmurs. Dyspnoea which occurs in severely anaemic patients may be a sign of cardio-respiratory failure. Tissue hypoxia is the end result of the blood’s reduced oxygen carrying capacity. The compensatory mechanisms in response to hypoxia cause the clinical manifestations to develop. An anaemic individual will have the following two key compensatory mechanisms; 2. The skin A common sign is generalised pallor due primarily to vasoconstriction with redistribution of blood to key areas (brain, myocardium).
  1.A rapid onset: Anaemia that develops over a short period of time will cause more symptoms than more slowly progressing anaemia because there is less time for the O2 dissociation curve of haemoglobin and the cardiovascular system to adapt. 2.Severity: Mild anaemia (Hb 9.0-11.0 g/dL) often produces no symptoms or signs. In a young person, severe anaemia may not even present clinically. However this is notoriously unreliable and some patients with severe anaemia may compensate well while others with mild anaemia may present with severe symptoms. 3.Age: The elderly are less tolerable of anaemia mainly as a result of an inability to increase cardiac output. 4. Co-existent disease - often cardiac or pulmonary disease. |Clinical features of anemia In general, a healthy individual may compensate well for anaemia and remain mostly asymptomatic. However many of the following symptoms and signs are observable when the following occurs;
| Clinical features of anemia General symptoms and signs General Symptoms Weakness and lethargy Shortness of breath: particularly on exercise. Headaches Palpitations Confusion and symptoms of cardiac failure in elderly Some specific signsGeneral Signs
| Clinical features of anemia Signs: Pallor of mucous  membranes (most  common sign). This is a  general sign.   Beware: pallor is quite  subjective and NOT a  reliable clinical sign.  Be  careful not to exclude  anaemia on the basis of  absence of pallor alone
| Clinical features of anemia Signs: Nail bed; demonstrating  koilonychia (spoon- shaped nails).  This is  specific to iron  deficiency.
| Clinical features of anemia Signs Atrophic glossitis; red large swollen tongue. This is seen in both vitamin B12 and folate deficiency.
| Clinical features of anemia Signs Angular stomitis; fissuring at corners of mouth. This is seen in both vitamin B12 and folate deficiency.
| clinical features of anemia Signs Dysphagia: pharyngeal web (Paterson-Kelly syndrome). This occurs in iron deficiency.
| clinical features of anaemia Signs Peripheral oedema. A general sign.
| Clinical features of anemia Signs High flow murmur, bounding pulse and/or tachycardia: All features of a compensatory hyperdynamic circulation. These are general signs!
An adult male will be anaemic if they have a haemoglobin of < 11.5 g/dl on a full blood count. Within the developing world iron deficient anaemia is the single greatest cause of anaemia The respiratory system is the main physiological compensator in anaemia. Koilonychia, glossitis, angular stomatitis are all general signs of anaemia. Some key signs associated with iron deficient anaemia are koilonychia and glosso-pharyngeal webbing. False! An adult male is anaemic if [Hb] is < 13.5 g/dl. An adult female will be considered anaemic if [Hb] is < 11.5 g/dl. True! False! The cardiovascular system is the major adaptor. Both stroke volume and heart rate increase in an attempt to mobilize greater volumes of oxygenated blood to the tissues. False! Koilonychia is sign of iron deficiency. Glossitis and angular stomatits are a sign of vitamin B12 and folate deficiency. True! true false
|Classification of anaemia Essentially there are two ways to classify anaemia, by red cell size (morphological classification) or by cause (aetiological classification). Both have their purpose and both need to be fully understood to gain a rounded understanding of anaemia. Morphological classification This is a practical and clinically useful classification for establishing a differential diagnosis of anaemia. It is done by examining red cells in a blood stained smear and by automated measurements of red cell indices Aetiological classification This classification is based on cause and illuminates the pathological process underlying anaemia. *Key point: In order to understand this classification it is essential to understand red cell indices reported in the complete blood count (CBC). There is great reward in understanding these indices as they enable one to identify some of the underlying processes leading to anaemia and, importantly, help to formulate a differential diagnoses.
MCV: Mean cell volume; the average volume of the red cells. MCV does not provide an indicator of either haemoglobin concentration within the cells, or the number of red cells. It enables us to categorize red cells into the following; Microcytic (MCV <80fL) a small red blood cell. Normocytic (MCV of 80-99fL) a normal size red blood cell. Macrocytic (MCV > 99fL) a large red blood cell. This is a key index that is used daily in medical settings across the world to categorize the type of anaemia present. It is reliable in most cases; one exception is when two pathologies occur at the same time such as vitamin B12 and Iron deficiency. MCV reports average cell volume; further assessment of cell size and how this varies within an individual can be ascertained from the red cell distribution width (RDW; see below). MCH: Mean corpuscular haemoglobin ( normal range 26.7-32.5pg/cell): the average haemoglobin content of red blood cells. Cells with a reduced haemoglobin content are termed hypochromic and those with a normal level are termed normochromic (see below). |Red cell indices RDW: Red cell distribution width; an index of the variation in sizes of the red cell population within an indiviual. This will be raised if two red cell populations are present. Occasionally useful if there is doubt about multiple causes of anaemia. A common cause for an increased RDW is the presence of reticulocytes. Normochromic implies normal staining of the cells in a thin blood film. The central area of pallor is normally about 1/3 of the cell diameter Hypochromic indicates reduced staining with increase in the central area of pallor These are the key measures of red cell indices. They relate to the haemoglobin content and size of the red blood cells.
|Interpretation of red cell indices Microcytosis & hypochromia Normocytosis & normochromia Microcytic Abnormally small red blood cells. Microcytic anemia is not caused by reduced DNA synthesis. It is not fully understood but is believed to be due reduced erythroid regeneration. Hypochromic Hypochromic cells due to a failure of haemoglobin synthesis. Pathologies; •Iron deficiency; iron is an essential building block of haem. •Failure of globin synthesis; this occurs in the thalassemia's. •Crystallization of haemoglobin: sickle cell disease and haemoglobin C. Normocytic Many processes causing anaemia do not effect the cell size or haemoglobin concentration within cells. Normocytic normochromic anaemia develops when there is a decrease in the production of normal red blood cells. Pathologies; •anemia of chronic disease (some) •aplastic anemia •Haemolysis: a increased destruction (some) •Hemolysis ;or loss of red blood •pregnancy/fluid overload: an inbalance or an increase in plasma volume compared to red cell production Macrocytosis & megaloblastosis Macrocytic megaloblastic red blood cells have an unusual misshapen appearance, which is due to defective synthesis of DNA. This in turn leads to delayed maturation of the nucleus compared to that of the cytoplasm and the cells have a reduced survival time. Macrocytosis: The exact cause of the pathological mechanisms behind these large cells is not fully understood.. It is thought to be linked to lipid deposition on the red cell membrane. Alcohol is the most frequent cause of a raised MCV!   Alcohol | Liver disease | hypothyroidism | Hypoxia | cytotoxic drugs | pregnancy | In clinical practice megaloblastic anaemia is almost always caused by a deficiency of vitamin B12 or folate which are key building blocks in DNA synthesis.
Megaloblastic Anemias • A form of anemia characterized by the presence of large, immature, abnormal red blood cell progenitors in the bone marrow • 95% of cases are attributable to folic acid or vitamin B12 deficiency
| Morphological classification of anemia Anaemia type Red cell indices Common examples Microcytic hypochromic MCV < 80 fl MCH < 27 pg/L Iron deficiency Thalassaemia Sideroblastic Normocytic normochromic Macrocytic MCV > 98 fl Folate deficiency B12deficiency Normal Haemolysis Chronic disease Marrow infiltration Megaloblastic
|Etiological classification of anemia This classification is based on cause and illuminates the pathogenic process leading to anaemia. You can look at anaemia from a production, destruction or pooling point of view. Reduced Production Insufficient production: If you consider the bone marrow to be the factory it must have enough raw material (Iron, vitamin B12 and folate) to make new blood cells. These raw material are called haematinics. If there is not enough of the raw material (a deficiency of one or more of the haematinics), then there is insufficient production. Inefficient production (erythropoiesis): some problem with maturation of the erythroid in the marrow. Occurs in bone marrow infiltration (malignancy/leukaemia), aplastic anaemia or in the macrocytic megaloblastic anaemia. Destruction  Reduced Cell lifespan This is either due to loss of red blood cells in a haemorrhage (a bleed) or the excessive destruction of red blood cells in haemolysis. Haemolysis is an important cause of red cell destruction and anaemia.  
Reduced bone marrow erythroid cells •aplastic anaemia •Leukaemia or malignancy Loss of red cells due to bleeding Increased destruction of red cells (haemolytic anaemia Failure of production of red cells by the bone marrow Dilution of red cells by increased plasma volume (e.g. hypersplenism) Nutritional (haematinic) deficiency •Iron •vitamin B12 •folate Ineffective red cell formation •Chronic inflam. •Thalassaemia •renal disease Immune Non- immune • Autoimmune warm • Autoimmune cold • Adverse drug reaction • Haemolytic disease of the newborn • Malaria • Burns • Mechanical heart valve • Hypersplenism • PNH Abnormal red cell membrane Abnormal haemoglobin Abnormal red cell metabolism • Sperocytes • Elliptocytes Thalassaemia •Sickle cell anaemia • Pyruvate kinase deficiency • G6PD deficiency Inherited / inside the cell Acquired / outside cell Anemia |Classification of anemia based on pathology
Normal CBC
Microcytic Anemia (IDA)
Macrocytic Anemia (Meg.):
|anaemia essential bites iron deficieny R.C.I.: a microcytic hypochromic anaemia Epi: One of the most common autosomal inherited disorders. Common in Mediterranean, Africa and middle east. Gene carriers are protected from p.falciprum malaria. Path: Reduced beta globin (of haemoglobin) production. Ineffective erythropoiesis and haemolysis IX. blood film, Hb electropheresis Si/Sy. Heterozygotes: often asymptomatic, mild anaemia, low MCV. Homozygote: severe anaemia, failure to thrive in first 6 months of life, splenomegaly, bone hypertrophy (secondary to extramedullary haemopoisis). Tx. For major Thalassaemia treat with repeated blood transfusion and iron chelation. Β-Thalassaemia R.C.I.: a microcytic hypochromic anaemia Aet: A group of autosomal recessive genetic disorders due to a haemoglobin chain mutation. Part of the haemoglobinopathies that primarily affect those of African origin (sickel cell trait can afford some protection against malaria. Path: Abnormal haemoglobin (HbS) undergo a sickling transformation in a deoxygenated state and a permenant conformational change of shape. The red cell looses its ability to deform becoming rigid. This can cause occlusion of small vessels. These crises are precipitated by hypoxia, dehydration, infection and the cold. IX. Electropherisis, haemoglobin solubility test. Si/Sy: Bone pain, if chronic haemolysis- jaundice and pigment gallstones. Txt Supportive; analgesia, fluids and antibiotics if required. Sickle cell disease Epi: the most common cause of a naemia worldwide affecting around 500million daily. Aet: pernicious anaemia, malabsorpion, post total gastrectomy Ix.  B12MCV  platelets. IF antibodies, folate levels Si/Sy: Gradual deterioration, Irritability, Loss of memory, Painless jaundice, Loss of sensation , Feeling of pins and needles in extremities. ataxic Txt Intramuscular (IM) of 1mg of hydroxycobalamin (Vitamin B12). There is no oral form. Vitamin B12 & Folate deficiencyEpi: Aet: increased consumption (pregnancy), dietary deficiency, folate antagonist (drugs eg; methotrexate). Ix.  folateMCV  transferrin saturation. Endoscopy/ colonoscopy if suspected blood loss. Si/Sy: Gradual deterioration, Irritability, Loss of memory, Painless jaundice, Loss of sensation , Feeling of pins and needles in extremities. ataxic Txt Intramuscular (IM) of 1mg of hydroxycobalamin (Vitamin B12). There is no oral form. Path G6PD is a key enzyme in the hexose monophosphate shunt. An important funtion of the shunt is maintain a health haemoglobin by removing oxidant stresses. Wihtout the enzyme, Hb breakdown resulting in haemolytic aneamia. Aet: X-linked Ix. Direct assay during haemolysis Si/Sy: Koilonychia, sore tongue, angular stomatitis, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Rx Avoid precipitants of oxidative stress; drugs (anti-malarials, analgesics), fava beans. Tx. Blood transfusion if required. G6PD deficieny Epi: the most common cause of anaemia worldwide affecting around 500million daily. Aet: The most common cause of iron deficient anaemia is BLOOD loss reduced intake (diet) Increased demand (pregnancy) Malabsorption (coeliac, gastrectomy) Ix. FBC, ferritin,  serum iron, TIBC,  transferrin saturation. Endoscopy/colonoscopy if suspected blood loss. Si/Sy: Koilonychia, sore tongue, angular stomatitis, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Txt Treat underlying cause, give ferrous sulphate until Hb and MCV normal. Hereditary spherocytosis; Microcytic anaemia Macrocytic anaemia Haemolytic anaemias Epi: the most common cause of anaemia worldwide affecting around 500million daily. Aet: The most common cause of iron deficient anaemia is BLOOD loss reduced intake (diet) Increased demand (pregnancy) Malabsorption (coeliac, gastrectomy) Ix. FBC, ferritin,  serum iron, TIBC,  transferrin saturation. Endoscopy/colonoscopy if suspected blood loss. Si/Sy: Koilonychia, sore tongue, angular stomatitis, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Txt Treat underlying cause, give ferrous sulphate until Hb and MCV normal. Aquired Haemolytic anaemias; KEY R.C.I. Red Cell IndicesEpi. Epidemiology Aet. Aetiology Ix. Investigations Si/Sy. Signs and Symptoms Path. Pathology Tx. Treatment
Iron deficient anemia; an overview Colon cancer microcytic hypochromic blood film.
R.C.I.: a microcytic hypochromic anaemia Epi: One of the most common inherited disorders. Common in Mediterranean, Africa and Middle East. Path: Reduced beta globin (of haemoglobin) production. Ineffective erythropoiesis and haemolysis Ix. blood film, Hb electrophoresis Si/Sy. Heterozygotes: often asymptomatic, mild anaemia, low MCV. Homozygote: severe anaemia, failure to thrive in first 6 months of life, splenomegaly, bone hypertrophy (secondary to extramedullary haemopoiesis). Tx. β-thalassaemia major requires repeated blood transfusion and iron chelation. Β-Thalassaemia
R.C.I.: a microcytic hypochromic anaemia Aet: Autosomal recessive genetic disorders due to mutation of the gene for HbA. Affect primarily people of African origin. Sickle cell trait (HbAS) affords strong protection against malaria. Path: Abnormal haemoglobin (HbS) undergoes a sickling transformation when in a deoxygenated state resulting in a permanent conformational change of shape. The red cell looses its ability to deform becoming rigid. This can cause occlusion of small vessels and result in sickle cell crises precipitated by hypoxia, dehydration, infection and the cold. IX. Electrophoresis, haemoglobin solubility test. Si/Sy: Bone pain, jaundice, pigment gallstones, leg ulcers, dactylitis in infants. Txt Supportive; analgesia, fluids and antibiotics during crises. Sickle cell disease (HbSS); an overview Dactylitis in a child Blood film: sickle cells
path: Vitamin B12 binds to IF intrinsic factor in the stomach and is absorbed in the terminal ileum Aet: Pernicious anaemia, malabsorpion, post total gastrectomy Ix.  B12MCV  platelets. IF antibodies. Check folate levels. Si./Sy: Gradual deterioration, Irritability, Loss of memory, Painless jaundice, Loss of sensation , Feeling of pins and needles in extremities, ataxic. Txt. Intramuscular (IM) of 1mg of hydroxycobalamin (Vitamin B12). There is no oral form. Vitamin B12 deficiency Aet: increased consumption (pregnancy), dietary deficiency, folate antagonist (drugs eg; methotrexate, alcohol). Ix. serum folate, red cell folate. MCV Si/Sy: Jaundice. Weight loss. GI disturbances. Glossitis. Txt. Folic acid supplementation. Exclude Vitamin B12 eficiency first. Folate deficiency Glossitis. Blood film; Macrocytic hypochromic
Path G6PD is a key enzyme in the hexose monophosphate shunt. An important function of the shunt is maintain healthy haemoglobin by protection from oxidant stress. In G6PD deficiency, haemolytic anaemia occurs. Aet: X-linked Ix. Direct assay of G6PD activity Si/Sy: None other than those of acute / chronic anaemia Rx Avoid precipitants of oxidative stress; drugs (anti-malarials, analgesics), fava beans. Tx. Blood transfusion if required. G6PD deficient anaemia; an overview Drugs Fava beans
Epi: 1 in 5000 people in Northern Europe. Aet: Autosomal dominant Path.Defective cell membrane protein (spectrin) causes a loss of cell membrane, progressive spherocytosis and eventually premature death (haemolysis). Increased sensitivity to infections such as parvo-virus. IX.Blood film; spherocytes Increased osmotic fragility. negative antiglobulin test. Si/Sy: asymptomatic.Jaundice, splenomegaly General features of anaemia Txt Give ferrous sulphate , ferritin if deficiency Hereditary spherocytosis; an overview Blood film
WARM Aet: associated with the production of autoantibodies of IgG. They attach to the red cell at body temp and are removed early by the reticuloendothelial system. Path: Idiopathic or precipitated by drugs or autoimmune disease, leukaemia. IX. Bloods: unconjugated haemoglobin, LDH, Reticulocytes. Positive direct antiglobulin test. Si/Sy: Jaundice, general features, splenomegaly Txt Steroids, splenectomy as 2nd line. Vaccination against H. Influenza, Men C and Pneumococcus. Autoimmune haemolytic anaemia; an overview These anaemias can be split into ‘warm’ and cold’ types. This is dependent on the temperature at which the antibody reacts with the body. COLD Aet: Associated with the production of autoantibodies of IgM and are removed early by the reticuloendothelial system. Usually self-limiting. Path: Idiopathic or secondary to infection or lymphoma. IX. Bloods: unconjugated haemoglobin, LDH, Reticulocytes. Positive direct antiglobulin test. Si/Sy: Worse in cold weather, acrocyanosis (purpling of skin), Reynaud's phenomenon. Txt Remove precipitants, keep patient warm, consider immunosuppression.
Microcytosis is MCV < 90fL The appearance of a hypochromic red blood cell is caused by reduced DNA synthesis In vitamin B12 deficiency you would expect the MCV to be >99fL Both sickle cell anaemia and thalassaemia have abnormal haemoglobin A macrocytic blood film may indicate excess alcohol consumption or liver disease False! Microcytosis is MCV < 80fL. False! A hypochromic film is due to reduced haemoglobin content within red blood cells. True! True! True! true false
|Glossary Anemia: a haemoglobin concentration in peripheral blood below normal range for sex and age Hemoglobin: a metalloprotien inside a red blood cell that is responsible for oxygen delivery. It is composed of four globulin chains each containing an iron containing haem group. Macrocytic: Red cells of average volume (MCV) above normal. Mean cell volume: the average volume of circulating red cells Mean Corpuscular Haemoglobin (MCH): The average haemoglobin content of red blood cells. Microcytic: red cells of average volume (MCV) below normal Normoblast: nucleated red cell precursor normallyy found in the bone marrow Poikilocytosis: variation in shape of peripheral blood red cells Reticulocyte: a non-nucleated young red blood cell still containing RNA. Can be found in the peripheral blood and bone marrow. Stem cell: resides in the bone marrow and by division and differentiation gives rise to all the blood cells Sickle cell disease: an inherited disorder of haemoglobin of varying severity. The name arises from the deformed shape of the red blood cell takes when the abnormal haemoglobin inside them polymerizes at low oxygen concentrations. Thalassaemias: a spectrum of inherited disorders of haemoglobin where there is an inbalance in globin chain production.
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Anemias

  • 1.
    Dr. Suhail S.Kishawi Consultant in Endocrinology and DiabetesConsultant in Endocrinology and Diabetes ‫دد‬‫د‬‫د‬‫د‬‫د‬‫دد‬‫د‬‫د‬‫د‬‫دد‬‫د‬‫د‬‫د‬‫د‬‫د‬‫د‬‫د‬‫د‬ ‫ييييييي‬ ‫يييييي‬ ‫ييييي‬ ‫ييييييي‬ ‫يييييييي‬ ‫ييييييي‬ ‫ييييييي‬ Anemias
  • 2.
    The Blood Plasma Red bloodcell White blood cell Platelets
  • 3.
    Red Blood Cells Containhaemoglobin, a molecule specially designed to hold oxygen and carry it to cells that need it. Can change shape to an amazing extent, without breaking, as it squeezes single file through the capillaries. A biconcave disc that is round and flat without a nucleus
  • 4.
    White Blood Cells Thereare many different types and all contain a big nucleus. The two main ones are the lymphocytes and the macrophages. Some lymphocytes fight disease by making antibodies to destroy invaders by dissolving them. Other lymphocytes make antitoxins to break down poisons. Macrophages ‘eat’ and digest micro-organisms .
  • 5.
    Platelets Platelets are bitsof cell broken off larger cells. Platelets produce tiny fibrinogen fibres to form a net. This net traps other blood cells to form a blood clot.
  • 6.
    Plasma A straw- coloured liquid that carriesthe cells and the platelets which help blood clot. • Carbon dioxide • Glucose • Amino acids • Proteins • Minerals • Vitamins • Hormones • Waste materials like urea. It also contains useful things like;
  • 7.
    | Introduction   Anaemia canbe defined as a reduction in the haemoglobin in the blood below normal range for age and sex. Essentially, anaemia is defined as haemoglobin (Hb) concentration: For adult males < 13.5 g/dl For adult women < 11.5 g/dl Anaemia is a global public health problem affecting both developing and developed countries. It has major consequences for human health as well as social and economic development. In 2008, iron deficiency anaemia was considered to be among the most important contributing factors to the global burden of disease. Image above: scanning electron microscope image of red blood cells. Image left: Global WHO map of anaemia in preschool age children.
  • 8.
    | The Erythrocyte:An Overview Image: scanning electron microscope of red blood cell To achieve these functions the red cell has several unique properties…. Strength: it has a strong but flexible membrane able to withstand the recurrent shear forces involved in the circulation of blood. Flexibility: the red cell is 7.8 µm across and 1.7 µm thick and yet it is able to fit through capillaries of only 5 µm diameter. This is in-part due to the flexible membrane and shedding of the nucleus. Biconcave shape: increases surface area available for gaseous exchange. Haemoglobin content: unique to the red cell, it is this metaloproteinmetaloprotein molecule which is pivotal in red cell development and Oxygen transport due to its affinity for O2. Function   The primary function of the erythrocyte is the carriage of oxygen from the lungs to the tissues and CO2 from the tissues to the lungs.  The red cell also plays an important role in pH buffering of the blood. Lifespan: Because the fully developed red blood cell has no nucleus the cell cannot divide or repair itself. The lifespan is therefore relatively short (120 days).
  • 9.
    Kidney Bone marrow Red bloodcells in circulationerythropoietin Stem cells Erythroid precursors An erythrocyte is a fully developed, mature red blood cell. The adult human makes approximately 1012 new erythrocytes every day by the process of erythropoiesis. This is a complex process that occurs within the bone marrow. Before an erythrocyte arrives fully functioning into the blood stream it must develop from a stem cell through an important number of stages As with much human physiology, this system works via a feedback mechanism. 4. There is no store of EPO. The production of erythropoietin is triggered by tissue hypoxia (oxygen tension sensed within the tubules of the kidney) and stops when oxygen levels are normal. | Erythropoiesis 2. EPO stimulates stem cells within the bone marrow which differentiate into erythroid precursors. 3. EPO continues to stimulate primitive erythroid cells (red blood cells) in the bone marrow and induce maturation. 1: Erythropoietin (EPO), a growth factor, is synthesized primarily (90%) from peritubular cells of the kidneys (renal cortex). Macrophages surround and supply iron to these erythroprogenitor cells that become erythroblastic islands.
  • 10.
    | Production oferythrocyts :Erythropoiesis
  • 11.
    | Erythropoiesis Keypoint! In chronicstates of anaemia the opposite may occur. The chronic hypoxic state increases production of EPO. This leads to an increase in the proportion of erythroblasts, expansion and eventually fatty deposition within the bone marrow. During childhood when the growth plates are still present, this expansion can lead to bone deformities such as frontal bossing. This is seen in chronic haemolysis such as thalassaemia. Keypoint! Chronic renal disease / bilateral nephrectomy will reduce or stop the production of EPO. It’s absence or reduction causes anaemia through reduced red cell production. Anaemia due to EPO deficiency will be normocytic in morphology; i.e. the red cell will be a normal shape and size but reduced in number. Hypoxia is the major stimulant for increased EPO production Kidney Bone marrow erythropoietin Erythroid precursors Stem cells Kidney Bone marrow erythropoietin Erythroid precursors Stem cells
  • 12.
    |Red cell precursorsand the sequence of erythropoiesis Anaemia of chronic disease. In individuals living with a chronic disease (e.g. rheumatoid arthritis),a complex interaction of inflammatory cytokines interferes with the red cell lifecycle by impairing iron metabolism and inhibiting red cell precursors. The end result is a normocytic anaemia. Reticulocytes are an important cell in haematology as they increase in number following a haemorrhage, haemolytic anaemia or from treatment of a haematinic deficiency. They provide an excellent measure of red cell production and the age of the red cell population. In normal blood there is usually about 1 reticulocyte : 100 erythrocytes. Key point! Keypoint! marrow 3.5 Erythrocyte: after 1 week the mature erythrocyte emerges with no organelles and high haemoglobin content.Sequence: amplification and maturation of the erythrocyte Pronormoblast: This is the earliest and largest cell with a large nucleus and no haemoglobin. 3.4. Reticulocytes: Considered the “teenagers” of the the life cycle! This is the FINAL stage of developmentThis is the FINAL stage of development before full maturation.before full maturation. These cells are now anucleate and contain roughly 25% of the final haemoglobin total. They reside mostly in the marrow but in healthy individuals a small number can be found in the peripheral blood. They contain some cell organelles. Normoblasts: these cells go through a large number of progressive changes. Fundamentally they reduce in cell size but increase the haemoglobin concentration in the cytoplasm. The nucleus proportionally decreases until it is extruded before the cell is released in to the blood. blood
  • 13.
    |Haematinics Vitamin B12 (cobalamin)and folate (pteroylglutamic acid): These are key building blocks for DNA synthesis and essential for cell mitosis. DNA synthesis is reduced in all cells that are deficient in either folate or vitamin B12. The bone marrow is the factory for blood cell production. In haematinic deficiency, DNA replication is limited and hence the number of possible cell divisions is reduced leading to larger red cells being discharged into the blood i.e. less DNA, less divisions and larger cells. This leads to enlarged, misshapen cells or megaloblasts in the marrow and macrocytic red cells in the blood. •So what exactly are the haematinics? These are the key micronutrients that must be present if a red blood cell and its haemogoblin are to develop in a normal fashion. • These major micronutrients, provided in a balanced diet, are iron, vitamin B12 and folate • A deficiency in any one of these micronutrients can result in anaemia through impaired red cell production within the bone marrow • Assessing haematinic status is key to the investigation of the cause of anaemia Iron: At the centre of the haem molecule is an atom of iron which binds oxygen in a reversible manner. Haemoglobin concentration in the developing red cell is a rate limiting step for erythropoiesis. In iron deficiency, red cells undergo more divisions than normal and, as a result, are smaller (microcytic) and have a reduced haemoglobin content (hypochromic). Iron deficiency is the leading cause of anaemia worldwide. Erthropoiesis is also regulated by the availability of haematinics “Check the haematinics” this is a phrase used frequently on the hospital ward!
  • 14.
    |Haematinics in haemoglobin IronProtoporphyrin GlobinHaem Haemoglobin Thalassaemia • Iron deficiency • Chronic inflammation • Malignancy Chronic infections and inflammatory disorders cause chronic anaemia as a result of; 1. Slightly shortened red blood cell life span 2. Sequestration of iron in inflammatory cells called macrophages Both procedures result in A decrease in the amount Of iron available to make Red blood cells.
  • 15.
    |Haematinics: the normaliron cycle Iron deficiency can be identified best by assessing the appearances of the red cells on a blood film. Iron indices in a blood sample are helpful to confirm a lack of iron. In order to interpret these indices, it is vital to understand how the body handles iron ….. Erythroid bone marrow (normoblasts) Reticuloendothelial system; Spleen & macrophages Duodenum Serum transferrin Fe Red blood cells Liver Iron is a key constituent of haemoglobin (60-70% of total body iron is stored here) and it’s availability is essential for erythropoiesis. In iron deficiency, there are more divisions of red cells during erythropoiesis than normal. As a result the red cells are smaller (microcytic) and have a reduced haemoglobin content (hypochromic). 2. Iron is then attached to a protein, transferrin in the serum (plasma), where it is transported to the bone marrow for haemoglobin synthesis. 1. Iron is absorbed from the small intestine in the ferrous state (Fe2+ ; approx. 1mg/day). 3. Dying red cells are recycled by macrophages in the spleen and iron is recycled into the plasma for further use. Soluble transferrin receptors, sTfR are on the red cell surface. These can be measured and are increased in iron deficiency. An iron deficiency profile. Serum Iron: Reduced Serum total iron- binding capacity (TIBC): Increased- the body works hard to bind free iron. Serum ferritin: Reduced-since iron stores are low Serum soluble transferrin receptors: Increased-since red cells attempt to absorb more iron. In iron deficient states, bone marrow iron is reduced. Some iron binds to apoferritin to form ferritin, a storage compound.
  • 16.
    Fe+2 Fe+2 Fe+2Fe+2 Dissociation Passive diffusion Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Gut LumenMucosal Cell Blood Ferritin Iron salts Fe+3 Free Radical Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+2 Fe+3 Free Radical Transferrin Incorporation into Hb
  • 17.
    There are anumber of key steps in the absorption of Vitamin B12. The two key locations are the stomach and the terminal ilium. Dietary vitamin B12 binds with intrinsic factor (IF) in the stomach, a transport protein produced by gastric parietal cells. The B12-IF complex then travels through the small intestine and is absorbed by special receptors in the distal ileum. This pathway is important when considering possible causes of Vitamin B12 deficiency. Vitamin B12 deficiency can take up to two years to develop as the body has sufficient stores for this period. Distal ileum Site of B12 absorption Oesophagus Stomach IF Intrinsic factor Vitamin B12 ingested |Haematinics: vitamin B12 Pernicious anaemia: the leading cause of B12 deficiency. IgG autoantibodies target gastric parietal cells and its product IF causing an atrophic gastritis. This results in reduced secretion of intrinsic factor and therefore reduced B12-IF complex for absorption in the distal ileum. Causes of vitamin B12 deficiency 1.Pernicious anaemia 2.Inadequate intake 3.Poor absorption
  • 18.
    • Gives redblood cells their colour • Can carry up to 4 molecules of O2 • Associates and dissociates with O2 • Contains iron |Haemoglobin
  • 19.
  • 20.
    When there isa high concentration of oxygen e.g in the alveoli haemoglobin combines with oxygen to form oxyhaemoglobin. When the blood reaches the tissue which have a low concentration of oxygen the haemoglobin dissociates with the oxygen and the oxygen is released into body tissues Function of Haemoglobin
  • 21.
    | Haemoglobin andO2 transport A key function of a red cell is to carry and deliver oxygen to the tissues and return CO2 from the tissues to the lungs. As a result the red cell has developed a specialised molecule called haemoglobin (Hb). It is important to gain a basic understanding of its synthesis, functioning and metabolism as errors in these processes lead to a number of anaemic states. It’s waste products are also released when a red cell is destroyed prematurely and are therefore a valuable indicator of haemolysis.   2,3-DPG oxyhaemoglobin deoxyhaemoglobin A molecule called 2,3 –  Diphosphoglycerate  (2,3-DPG) sits between  the β chains and when  increased helps to  offload oxygen to the  tissues. HAEM MOLECULE Each individual globin combines with one haem molecule. This molecule contains iron and binds oxygen in a reversible manner. A mature red cell. GLOBIN CHAIN A normal adult haemoglobin  (Hb A) molecule consists of 4 polypeptide (globin) chains:  α1α2 β1β2. Haemoglobinopathies Thalassaemia: reduced rate of synthesis of either α or β globin chains. Within this group of inherited conditions there may be both ineffective erythropoiesis and haemolysis resulting in a microcytic anaemia sometime also with hypochromia. Sickle cell disease: an inheritance of two abnormal β-globin genes (HbSS). The abnormality consists of a point mutation in the β globin gene. This results in Hb insolubility in it’s deoxygenated state with crystallization within the red cell causing sickling of the cell and vascular occlusion. A common problem that affects primarily the Afro-Caribbean populations. Keypoint! Oxygen (O2)
  • 22.
    |Ageing and death Haemolyticanaemias; This is an important group of anaemias. There are many important causes of premature red cell death resulting in anaemia and the increased products of haemolysis within the blood circulation and beyond. Haemolysis: any process that shortens the red blood cell lifespan to less than 120 days. A red cell shows signs of deterioration from around 100 days of the cell’s cycle. Without any DNA or ribosomes, the cell is unable to generate new enzymes (like pyruvate kinase or G6PD that we have been introduced to). These ageing cells are eventually identified by the reticuloendothelial system. This is a system of white blood cells that are present within the spleen, liver and lymph nodes whose main role is to phagocytose damaged or ageing cells. The tired red cells are removed and recycled by macrophages in the spleen and liver. Normally red cell degradation and recycling is managed by the reticuloendothelial system on a daily basis without any problems. When a pathological process causes premature lysis of the red cells, the ability of the body to clear the increased number of waste products may be overloaded.
  • 23.
    Haemoglobin Haem Unconjugated bilirubin Conjugated in theliver to the diglucuronide, water- soluble form that is secreted in the bile and then converted to stercobilinogen. Liver Some stercobilin and stercobilogen are reabsorbed from the intestine and excreted in the urine as urobilin and urobilinogen. Raised levels in the urine may indicate haemolysis. 3. Bilirubin Heamolysis results in excess bilirubin causing jaundice (typically lemon yellow colour ) and pigment gallstones. GlobinIron Attaches to transferrin F Is metabolized to amino acids Red blood cell Investigating haemolysis 1.Lactic acid dehydrogenase (LDH) 2.Reticulocyte count 3.Bilirubin 1. LDH is a nucleic enzyme which is released on red cell destruction. The concentration of LDH is measurable from a blood sample and provides an indicator of haemolysis. 3. LDH 2. Reticulocyte count will be elevated in response to the feedback loop during anaemia. The bone marrow increases red cell production. Reticulocytes are larger than mature red blood cells causing a rise in mean cell volume ( MCV). Flow diagram: products of red cell destruction. The protoporphyrin of haem is metabolised to the yellow pigment bilirubin, which is bound to albumin in the plasma. Stercobilinogen is excreted in the faeces Haptoglobins these proteins bind to any free haemoglobin. These proteins can become saturated in a haemolytic anaemia. Haemoglobin can then pass into the urine causing haemoglobinuria or converted to haemosiderinuria.
  • 24.
    A red bloodcell has an average lifespan of 80 days Erythropoietin (EPO) production is reduced in chronic hypoxic states Iron is transported in the blood bound to apoferritin. A low pH, a high CO2 concentration in the blood and a high number of 2,3-DPG would shift the oxygen dissociation curve to the left Vitamin B12 is absorbed in the jejunum Folate and vitamin B12 are key building blocks of haemoglobin Chronic anaemia and malignancy prevent haem production A deficiency in folate causes a macrocytic megaloblastic anaemia Adult haemoglobin is composed of 2 alpha and 2 beta chains Increased reticulocytes is a key feature of a haemolytic anaemia true / false False! A red blood cell has an average lifespan of 120 days. This is short compared to other blood cells due to the cell having no nucleus or organelles and is thus unable to replace key enzymes and maintain cell function. False! In chronic hypoxic states there is an increased production of EPO. This leads to an increase in the proportion of erythroblasts, expansion and eventually fatty deposition within the bone marrow. True! JAK 2 is a receptor for erythropoietin. A point mutation (tyrosine kinase) in this receptor is implicated in the oncogenisis of several myeloproliferative neoplasm. (90% of Polycythemia vera patients). False! It would shift to the right. All these factors would cause haemoglobin (Hb) to have a reduced affinity for O2 and increase O2 release fom Hb. False! Vitamin B12 binds to intrinsic factor in the stomach, travels through the small bowel and the complex is absorbed in the distal ileum. False! Vitamin B12 and folate are key building blocks of DNA. True! Chronic anaemia and malignancy block iron from being incorporated into the haem molecule. True! Both folate and vitamin B12 are key micronutrients for DNA synthesis. Deficiencies cause a macrocytic megaloblastic anaemia. True! The normal adult Hb contain 4 globin chains (often notated as α2β2). True! The cells will be elevated in response to our feedback loop during anaemia. With excessive destruction of red cells, the bone marrow increases production.
  • 25.
  • 26.
    |Clinical features ofanemia 1. The cardiovascular system Cardiac compensation is the major adaptation. Both stroke volume and heart rate increase mobilizing greater volumes of oxygenated blood to the tissues. This can present with palpitations, tachycardia and heart murmurs. Dyspnoea which occurs in severely anaemic patients may be a sign of cardio-respiratory failure. Tissue hypoxia is the end result of the blood’s reduced oxygen carrying capacity. The compensatory mechanisms in response to hypoxia cause the clinical manifestations to develop. An anaemic individual will have the following two key compensatory mechanisms; 2. The skin A common sign is generalised pallor due primarily to vasoconstriction with redistribution of blood to key areas (brain, myocardium).
  • 27.
      1.A rapid onset:Anaemia that develops over a short period of time will cause more symptoms than more slowly progressing anaemia because there is less time for the O2 dissociation curve of haemoglobin and the cardiovascular system to adapt. 2.Severity: Mild anaemia (Hb 9.0-11.0 g/dL) often produces no symptoms or signs. In a young person, severe anaemia may not even present clinically. However this is notoriously unreliable and some patients with severe anaemia may compensate well while others with mild anaemia may present with severe symptoms. 3.Age: The elderly are less tolerable of anaemia mainly as a result of an inability to increase cardiac output. 4. Co-existent disease - often cardiac or pulmonary disease. |Clinical features of anemia In general, a healthy individual may compensate well for anaemia and remain mostly asymptomatic. However many of the following symptoms and signs are observable when the following occurs;
  • 28.
    | Clinical featuresof anemia General symptoms and signs General Symptoms Weakness and lethargy Shortness of breath: particularly on exercise. Headaches Palpitations Confusion and symptoms of cardiac failure in elderly Some specific signsGeneral Signs
  • 29.
    | Clinical featuresof anemia Signs: Pallor of mucous  membranes (most  common sign). This is a  general sign.   Beware: pallor is quite  subjective and NOT a  reliable clinical sign.  Be  careful not to exclude  anaemia on the basis of  absence of pallor alone
  • 30.
    | Clinical featuresof anemia Signs: Nail bed; demonstrating  koilonychia (spoon- shaped nails).  This is  specific to iron  deficiency.
  • 31.
    | Clinical featuresof anemia Signs Atrophic glossitis; red large swollen tongue. This is seen in both vitamin B12 and folate deficiency.
  • 32.
    | Clinical featuresof anemia Signs Angular stomitis; fissuring at corners of mouth. This is seen in both vitamin B12 and folate deficiency.
  • 33.
    | clinical featuresof anemia Signs Dysphagia: pharyngeal web (Paterson-Kelly syndrome). This occurs in iron deficiency.
  • 34.
    | clinical featuresof anaemia Signs Peripheral oedema. A general sign.
  • 35.
    | Clinical featuresof anemia Signs High flow murmur, bounding pulse and/or tachycardia: All features of a compensatory hyperdynamic circulation. These are general signs!
  • 36.
    An adult malewill be anaemic if they have a haemoglobin of < 11.5 g/dl on a full blood count. Within the developing world iron deficient anaemia is the single greatest cause of anaemia The respiratory system is the main physiological compensator in anaemia. Koilonychia, glossitis, angular stomatitis are all general signs of anaemia. Some key signs associated with iron deficient anaemia are koilonychia and glosso-pharyngeal webbing. False! An adult male is anaemic if [Hb] is < 13.5 g/dl. An adult female will be considered anaemic if [Hb] is < 11.5 g/dl. True! False! The cardiovascular system is the major adaptor. Both stroke volume and heart rate increase in an attempt to mobilize greater volumes of oxygenated blood to the tissues. False! Koilonychia is sign of iron deficiency. Glossitis and angular stomatits are a sign of vitamin B12 and folate deficiency. True! true false
  • 37.
    |Classification of anaemia Essentiallythere are two ways to classify anaemia, by red cell size (morphological classification) or by cause (aetiological classification). Both have their purpose and both need to be fully understood to gain a rounded understanding of anaemia. Morphological classification This is a practical and clinically useful classification for establishing a differential diagnosis of anaemia. It is done by examining red cells in a blood stained smear and by automated measurements of red cell indices Aetiological classification This classification is based on cause and illuminates the pathological process underlying anaemia. *Key point: In order to understand this classification it is essential to understand red cell indices reported in the complete blood count (CBC). There is great reward in understanding these indices as they enable one to identify some of the underlying processes leading to anaemia and, importantly, help to formulate a differential diagnoses.
  • 38.
    MCV: Mean cellvolume; the average volume of the red cells. MCV does not provide an indicator of either haemoglobin concentration within the cells, or the number of red cells. It enables us to categorize red cells into the following; Microcytic (MCV <80fL) a small red blood cell. Normocytic (MCV of 80-99fL) a normal size red blood cell. Macrocytic (MCV > 99fL) a large red blood cell. This is a key index that is used daily in medical settings across the world to categorize the type of anaemia present. It is reliable in most cases; one exception is when two pathologies occur at the same time such as vitamin B12 and Iron deficiency. MCV reports average cell volume; further assessment of cell size and how this varies within an individual can be ascertained from the red cell distribution width (RDW; see below). MCH: Mean corpuscular haemoglobin ( normal range 26.7-32.5pg/cell): the average haemoglobin content of red blood cells. Cells with a reduced haemoglobin content are termed hypochromic and those with a normal level are termed normochromic (see below). |Red cell indices RDW: Red cell distribution width; an index of the variation in sizes of the red cell population within an indiviual. This will be raised if two red cell populations are present. Occasionally useful if there is doubt about multiple causes of anaemia. A common cause for an increased RDW is the presence of reticulocytes. Normochromic implies normal staining of the cells in a thin blood film. The central area of pallor is normally about 1/3 of the cell diameter Hypochromic indicates reduced staining with increase in the central area of pallor These are the key measures of red cell indices. They relate to the haemoglobin content and size of the red blood cells.
  • 39.
    |Interpretation of redcell indices Microcytosis & hypochromia Normocytosis & normochromia Microcytic Abnormally small red blood cells. Microcytic anemia is not caused by reduced DNA synthesis. It is not fully understood but is believed to be due reduced erythroid regeneration. Hypochromic Hypochromic cells due to a failure of haemoglobin synthesis. Pathologies; •Iron deficiency; iron is an essential building block of haem. •Failure of globin synthesis; this occurs in the thalassemia's. •Crystallization of haemoglobin: sickle cell disease and haemoglobin C. Normocytic Many processes causing anaemia do not effect the cell size or haemoglobin concentration within cells. Normocytic normochromic anaemia develops when there is a decrease in the production of normal red blood cells. Pathologies; •anemia of chronic disease (some) •aplastic anemia •Haemolysis: a increased destruction (some) •Hemolysis ;or loss of red blood •pregnancy/fluid overload: an inbalance or an increase in plasma volume compared to red cell production Macrocytosis & megaloblastosis Macrocytic megaloblastic red blood cells have an unusual misshapen appearance, which is due to defective synthesis of DNA. This in turn leads to delayed maturation of the nucleus compared to that of the cytoplasm and the cells have a reduced survival time. Macrocytosis: The exact cause of the pathological mechanisms behind these large cells is not fully understood.. It is thought to be linked to lipid deposition on the red cell membrane. Alcohol is the most frequent cause of a raised MCV!   Alcohol | Liver disease | hypothyroidism | Hypoxia | cytotoxic drugs | pregnancy | In clinical practice megaloblastic anaemia is almost always caused by a deficiency of vitamin B12 or folate which are key building blocks in DNA synthesis.
  • 40.
    Megaloblastic Anemias • Aform of anemia characterized by the presence of large, immature, abnormal red blood cell progenitors in the bone marrow • 95% of cases are attributable to folic acid or vitamin B12 deficiency
  • 41.
    | Morphological classificationof anemia Anaemia type Red cell indices Common examples Microcytic hypochromic MCV < 80 fl MCH < 27 pg/L Iron deficiency Thalassaemia Sideroblastic Normocytic normochromic Macrocytic MCV > 98 fl Folate deficiency B12deficiency Normal Haemolysis Chronic disease Marrow infiltration Megaloblastic
  • 42.
    |Etiological classification ofanemia This classification is based on cause and illuminates the pathogenic process leading to anaemia. You can look at anaemia from a production, destruction or pooling point of view. Reduced Production Insufficient production: If you consider the bone marrow to be the factory it must have enough raw material (Iron, vitamin B12 and folate) to make new blood cells. These raw material are called haematinics. If there is not enough of the raw material (a deficiency of one or more of the haematinics), then there is insufficient production. Inefficient production (erythropoiesis): some problem with maturation of the erythroid in the marrow. Occurs in bone marrow infiltration (malignancy/leukaemia), aplastic anaemia or in the macrocytic megaloblastic anaemia. Destruction  Reduced Cell lifespan This is either due to loss of red blood cells in a haemorrhage (a bleed) or the excessive destruction of red blood cells in haemolysis. Haemolysis is an important cause of red cell destruction and anaemia.  
  • 43.
    Reduced bone marrow erythroid cells •aplasticanaemia •Leukaemia or malignancy Loss of red cells due to bleeding Increased destruction of red cells (haemolytic anaemia Failure of production of red cells by the bone marrow Dilution of red cells by increased plasma volume (e.g. hypersplenism) Nutritional (haematinic) deficiency •Iron •vitamin B12 •folate Ineffective red cell formation •Chronic inflam. •Thalassaemia •renal disease Immune Non- immune • Autoimmune warm • Autoimmune cold • Adverse drug reaction • Haemolytic disease of the newborn • Malaria • Burns • Mechanical heart valve • Hypersplenism • PNH Abnormal red cell membrane Abnormal haemoglobin Abnormal red cell metabolism • Sperocytes • Elliptocytes Thalassaemia •Sickle cell anaemia • Pyruvate kinase deficiency • G6PD deficiency Inherited / inside the cell Acquired / outside cell Anemia |Classification of anemia based on pathology
  • 44.
  • 45.
  • 46.
  • 47.
    |anaemia essential bites irondeficieny R.C.I.: a microcytic hypochromic anaemia Epi: One of the most common autosomal inherited disorders. Common in Mediterranean, Africa and middle east. Gene carriers are protected from p.falciprum malaria. Path: Reduced beta globin (of haemoglobin) production. Ineffective erythropoiesis and haemolysis IX. blood film, Hb electropheresis Si/Sy. Heterozygotes: often asymptomatic, mild anaemia, low MCV. Homozygote: severe anaemia, failure to thrive in first 6 months of life, splenomegaly, bone hypertrophy (secondary to extramedullary haemopoisis). Tx. For major Thalassaemia treat with repeated blood transfusion and iron chelation. Β-Thalassaemia R.C.I.: a microcytic hypochromic anaemia Aet: A group of autosomal recessive genetic disorders due to a haemoglobin chain mutation. Part of the haemoglobinopathies that primarily affect those of African origin (sickel cell trait can afford some protection against malaria. Path: Abnormal haemoglobin (HbS) undergo a sickling transformation in a deoxygenated state and a permenant conformational change of shape. The red cell looses its ability to deform becoming rigid. This can cause occlusion of small vessels. These crises are precipitated by hypoxia, dehydration, infection and the cold. IX. Electropherisis, haemoglobin solubility test. Si/Sy: Bone pain, if chronic haemolysis- jaundice and pigment gallstones. Txt Supportive; analgesia, fluids and antibiotics if required. Sickle cell disease Epi: the most common cause of a naemia worldwide affecting around 500million daily. Aet: pernicious anaemia, malabsorpion, post total gastrectomy Ix.  B12MCV  platelets. IF antibodies, folate levels Si/Sy: Gradual deterioration, Irritability, Loss of memory, Painless jaundice, Loss of sensation , Feeling of pins and needles in extremities. ataxic Txt Intramuscular (IM) of 1mg of hydroxycobalamin (Vitamin B12). There is no oral form. Vitamin B12 & Folate deficiencyEpi: Aet: increased consumption (pregnancy), dietary deficiency, folate antagonist (drugs eg; methotrexate). Ix.  folateMCV  transferrin saturation. Endoscopy/ colonoscopy if suspected blood loss. Si/Sy: Gradual deterioration, Irritability, Loss of memory, Painless jaundice, Loss of sensation , Feeling of pins and needles in extremities. ataxic Txt Intramuscular (IM) of 1mg of hydroxycobalamin (Vitamin B12). There is no oral form. Path G6PD is a key enzyme in the hexose monophosphate shunt. An important funtion of the shunt is maintain a health haemoglobin by removing oxidant stresses. Wihtout the enzyme, Hb breakdown resulting in haemolytic aneamia. Aet: X-linked Ix. Direct assay during haemolysis Si/Sy: Koilonychia, sore tongue, angular stomatitis, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Rx Avoid precipitants of oxidative stress; drugs (anti-malarials, analgesics), fava beans. Tx. Blood transfusion if required. G6PD deficieny Epi: the most common cause of anaemia worldwide affecting around 500million daily. Aet: The most common cause of iron deficient anaemia is BLOOD loss reduced intake (diet) Increased demand (pregnancy) Malabsorption (coeliac, gastrectomy) Ix. FBC, ferritin,  serum iron, TIBC,  transferrin saturation. Endoscopy/colonoscopy if suspected blood loss. Si/Sy: Koilonychia, sore tongue, angular stomatitis, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Txt Treat underlying cause, give ferrous sulphate until Hb and MCV normal. Hereditary spherocytosis; Microcytic anaemia Macrocytic anaemia Haemolytic anaemias Epi: the most common cause of anaemia worldwide affecting around 500million daily. Aet: The most common cause of iron deficient anaemia is BLOOD loss reduced intake (diet) Increased demand (pregnancy) Malabsorption (coeliac, gastrectomy) Ix. FBC, ferritin,  serum iron, TIBC,  transferrin saturation. Endoscopy/colonoscopy if suspected blood loss. Si/Sy: Koilonychia, sore tongue, angular stomatitis, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Txt Treat underlying cause, give ferrous sulphate until Hb and MCV normal. Aquired Haemolytic anaemias; KEY R.C.I. Red Cell IndicesEpi. Epidemiology Aet. Aetiology Ix. Investigations Si/Sy. Signs and Symptoms Path. Pathology Tx. Treatment
  • 48.
    Iron deficient anemia;an overview Colon cancer microcytic hypochromic blood film.
  • 49.
    R.C.I.: a microcytichypochromic anaemia Epi: One of the most common inherited disorders. Common in Mediterranean, Africa and Middle East. Path: Reduced beta globin (of haemoglobin) production. Ineffective erythropoiesis and haemolysis Ix. blood film, Hb electrophoresis Si/Sy. Heterozygotes: often asymptomatic, mild anaemia, low MCV. Homozygote: severe anaemia, failure to thrive in first 6 months of life, splenomegaly, bone hypertrophy (secondary to extramedullary haemopoiesis). Tx. β-thalassaemia major requires repeated blood transfusion and iron chelation. Β-Thalassaemia
  • 50.
    R.C.I.: a microcytichypochromic anaemia Aet: Autosomal recessive genetic disorders due to mutation of the gene for HbA. Affect primarily people of African origin. Sickle cell trait (HbAS) affords strong protection against malaria. Path: Abnormal haemoglobin (HbS) undergoes a sickling transformation when in a deoxygenated state resulting in a permanent conformational change of shape. The red cell looses its ability to deform becoming rigid. This can cause occlusion of small vessels and result in sickle cell crises precipitated by hypoxia, dehydration, infection and the cold. IX. Electrophoresis, haemoglobin solubility test. Si/Sy: Bone pain, jaundice, pigment gallstones, leg ulcers, dactylitis in infants. Txt Supportive; analgesia, fluids and antibiotics during crises. Sickle cell disease (HbSS); an overview Dactylitis in a child Blood film: sickle cells
  • 51.
    path: Vitamin B12binds to IF intrinsic factor in the stomach and is absorbed in the terminal ileum Aet: Pernicious anaemia, malabsorpion, post total gastrectomy Ix.  B12MCV  platelets. IF antibodies. Check folate levels. Si./Sy: Gradual deterioration, Irritability, Loss of memory, Painless jaundice, Loss of sensation , Feeling of pins and needles in extremities, ataxic. Txt. Intramuscular (IM) of 1mg of hydroxycobalamin (Vitamin B12). There is no oral form. Vitamin B12 deficiency Aet: increased consumption (pregnancy), dietary deficiency, folate antagonist (drugs eg; methotrexate, alcohol). Ix. serum folate, red cell folate. MCV Si/Sy: Jaundice. Weight loss. GI disturbances. Glossitis. Txt. Folic acid supplementation. Exclude Vitamin B12 eficiency first. Folate deficiency Glossitis. Blood film; Macrocytic hypochromic
  • 52.
    Path G6PD isa key enzyme in the hexose monophosphate shunt. An important function of the shunt is maintain healthy haemoglobin by protection from oxidant stress. In G6PD deficiency, haemolytic anaemia occurs. Aet: X-linked Ix. Direct assay of G6PD activity Si/Sy: None other than those of acute / chronic anaemia Rx Avoid precipitants of oxidative stress; drugs (anti-malarials, analgesics), fava beans. Tx. Blood transfusion if required. G6PD deficient anaemia; an overview Drugs Fava beans
  • 53.
    Epi: 1 in5000 people in Northern Europe. Aet: Autosomal dominant Path.Defective cell membrane protein (spectrin) causes a loss of cell membrane, progressive spherocytosis and eventually premature death (haemolysis). Increased sensitivity to infections such as parvo-virus. IX.Blood film; spherocytes Increased osmotic fragility. negative antiglobulin test. Si/Sy: asymptomatic.Jaundice, splenomegaly General features of anaemia Txt Give ferrous sulphate , ferritin if deficiency Hereditary spherocytosis; an overview Blood film
  • 54.
    WARM Aet: associated withthe production of autoantibodies of IgG. They attach to the red cell at body temp and are removed early by the reticuloendothelial system. Path: Idiopathic or precipitated by drugs or autoimmune disease, leukaemia. IX. Bloods: unconjugated haemoglobin, LDH, Reticulocytes. Positive direct antiglobulin test. Si/Sy: Jaundice, general features, splenomegaly Txt Steroids, splenectomy as 2nd line. Vaccination against H. Influenza, Men C and Pneumococcus. Autoimmune haemolytic anaemia; an overview These anaemias can be split into ‘warm’ and cold’ types. This is dependent on the temperature at which the antibody reacts with the body. COLD Aet: Associated with the production of autoantibodies of IgM and are removed early by the reticuloendothelial system. Usually self-limiting. Path: Idiopathic or secondary to infection or lymphoma. IX. Bloods: unconjugated haemoglobin, LDH, Reticulocytes. Positive direct antiglobulin test. Si/Sy: Worse in cold weather, acrocyanosis (purpling of skin), Reynaud's phenomenon. Txt Remove precipitants, keep patient warm, consider immunosuppression.
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    Microcytosis is MCV< 90fL The appearance of a hypochromic red blood cell is caused by reduced DNA synthesis In vitamin B12 deficiency you would expect the MCV to be >99fL Both sickle cell anaemia and thalassaemia have abnormal haemoglobin A macrocytic blood film may indicate excess alcohol consumption or liver disease False! Microcytosis is MCV < 80fL. False! A hypochromic film is due to reduced haemoglobin content within red blood cells. True! True! True! true false
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    |Glossary Anemia: a haemoglobinconcentration in peripheral blood below normal range for sex and age Hemoglobin: a metalloprotien inside a red blood cell that is responsible for oxygen delivery. It is composed of four globulin chains each containing an iron containing haem group. Macrocytic: Red cells of average volume (MCV) above normal. Mean cell volume: the average volume of circulating red cells Mean Corpuscular Haemoglobin (MCH): The average haemoglobin content of red blood cells. Microcytic: red cells of average volume (MCV) below normal Normoblast: nucleated red cell precursor normallyy found in the bone marrow Poikilocytosis: variation in shape of peripheral blood red cells Reticulocyte: a non-nucleated young red blood cell still containing RNA. Can be found in the peripheral blood and bone marrow. Stem cell: resides in the bone marrow and by division and differentiation gives rise to all the blood cells Sickle cell disease: an inherited disorder of haemoglobin of varying severity. The name arises from the deformed shape of the red blood cell takes when the abnormal haemoglobin inside them polymerizes at low oxygen concentrations. Thalassaemias: a spectrum of inherited disorders of haemoglobin where there is an inbalance in globin chain production.
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