anil - haematology
Post on 24-Mar-2016
Embed Size (px)
DESCRIPTIONAnil - Haematology
MCD Year 2
1Haematology 1 - Iron deficiency
4Haematology 2 B12 & Folic Acid Deficiency
7Haematology 3 Haemoglobin and Thalassaemia
10Haematology 4 Abnormal White Cell Counts
14Haematology 5 - Blood Diagnostic Parameters
17Haematology 6 Anaemia and Polycythaemia
21Haematology 7 Haemostasis
25Haematology 8 Abnormalities of Haemostasis
29Haematology 9 Transfusion
Haematology 1 - Iron deficiency
1. Describe the role of iron in erythropoiesis.
2. List the dietary sources of iron, the factors influencing the absorption of iron, and the causes of iron deficiency.
3. Describe the clinical and haematological features of iron deficiency anaemia, and the diagnosis and management of iron deficiency.
4. Describe the clinical and haematological features of anaemia of chronic disease and explain how this is distinguished from iron deficiency.
IRON is mostly present in the body bound to haemoglobin Hb; therefore deficiencies of iron are primarily going to affect the haemoglobin and therefore the blood.
Each haem group is associated with a globin chain.
Erythropoiesis Iron binds to transferrin molecule
Transferrin binds to transferrin receptor on the erythroblasts and passes over the iron molecules.
Transferrin is released back into the circulation
Erythroblasts undergo erythropoiesis (become red blood cell).
Iron acts to increase the production of ferritin, and decrease the production of the transferrin receptor.Sources of Iron include
Cereal, fortifiedIron is absorbed in the duodenum.FACTORS AFFECTING ABSORPTION
- Increased.ACID e.g. orange juice
- DecreasedALKALINE e.g. tea, chapattisHaem is better absorbed than free iron (up to 10% absorption) and its absorption is not adversely affected by other food components. In contrast, non-haem iron (i.e. Fe2+ and Fe3+) from vegetable sources are less well absorbed (1-2% absorption) and may be affected by other dietary factors.
Iron stores: (3-5 grams)
haemoglobin & myoglobin (2-3 grams)
ferritin and haemosiderin (1 gram)
plasma bound protein iron including transferrin (3 milligrams)Causes of iron deficiency
BLOOD LOSS (heavy periods, haemorrhage,) DIET (vegans, vegetarians) INCREASED NEED (pregnancy) MALABSORBTION
Classic iron deficiency:
Transferrin saturation LOW
Treatment is generally IRON REPLACEMENT usually by oral route (ferrous sulphate tablets)
Anaemia of chronic disease is where there is no obvious cause apart from that the patient is unwell. It is normally associated with infection, inflammation or malignancy.
Classic anaemia of chronic disease:
LOW or N
HIGH or N
Transferrin saturation normal
1. RAISED C-reactive protein
2. RAISED Erythrocyte Sedimentation Rate
3. Acute phase response- INCREASES in
You can distinguish between anaemia of chronic disease and iron deficiency by using bone marrow aspirate.
It is caused by cytokines (such as TNF alpha and interleukins) that are released at times of infection, inflammation or malignancy. They prevent the flow of iron into red blood cells which in turn blocks iron utilization by:1. Stopping erythropoietin increase
2. Stopping iron flow out of cells
3. Increasing production of ferritin
4. Increasing death of red cellsHaematology 2 B12 & Folic Acid Deficiency
Anil Chopra1. Describe the role of vitamin B12 and folic acid in haemopoiesis, dietary sources and absorption of these vitamins, causes of deficiency, clinical and haematological features of vitamin B12 and folic acid deficiency and the diagnosis, further investigation and management of these deficiencies
2. Be able to explain that
a. Synthesis of DNA requires both vitamin B12 and folate
b. Integrity of the nervous system requires vitamin B12B12
Required for DNA synthesis
Required for the integrity of the nervous system.
Required for DNA synthesis
Required for Homocystine metabolism
Deficiency affects any cells which are rapidly dividing (bone marrow, epithelia of mouth and gut, embryos, gonads). Also leads to:
Anaemia: weak, tired, short of breath
Glossitis and angular cheilosis
Weight loss, change of bowel habit
Anaemia can either be MACROCYTIC or MEGALOBLASTIC
Macrocytic Anaemia generally defined by an increase in mean cell volume (MCV)This is usually measured by an automated full blood count. It can be caused by B12 or folate deficiency, liver disease, hypothyroidism, alcohol, drugs and haematological disorders.
Megaloblastic Anaemia - abnormal red cell development.
Normal Red Cell Development1) Proerythroblast: large cell with dark blue cytoplasm (high RNA content). It contains condensed chromatin.
2) Basophilic erythroblast: less RNA and more haemoglobin than proerythroblast.
3) Polychromatic Erythroblast: less RNA and more haemoglobin than basophilic erythroblast.
4) Pyknotic erythroblast: less RNA and more haemoglobin than polychromatic erythroblast. This moves out of the bone marrow.
5) Reticulocyte: nucleus is extruded completely and is found in the peripherals.
6) Mature Red blood Cells: formed from maturation of the reticulocytes.
In megaloblasic anaemia, the maturation (disappearance) of the nucleus does not happen at the same time as the development of the cytoplasm. The nucleus or parts of it are therefore visible (these cells are known as megaloblasts). These therefore die in the bone marrow and so red cell production increases to compensate by a process known as incomplete erythropoiesis.
White blood cells are also affected:
Hypersegmented neutrophils (nuclei have many segments)
Giant metamyelocytes (2-3 times their normal size)
Can be defined by high MCV, although cells vary in size (anisocytosis) along with low haemoglobin, and low white blood cell count. Causes include B12 or folate deficiency or drugs.
B12 and Folate Deficiencies
Caused by: inadequate intake
excessive loss / utilisation
Folate DeficiencyFolate is contained in fresh leafy vegetables and animal products but is destroyed by overcooking, canning or processing. Diagnosis:
Full blood count (folate levels)
Take history (look for alcoholism, skin disease, diet, illness, GI infection)
Consequences Megaloblastic, macrocytic anaemia
Neural tube defects in developing foetus
Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism.
All pregnant women take folic acid 0.4mg prior to conception and for the first 12 weeks
B12 DeficiencyB12 is found in animal products so vegans are at risk. It is mainly caused not by inadequate intake, but by inadequate absorption. Normally, most B12 absorption is done by intrinsic factor which is synthesised in the stomach. B12-IF then binds to ileal receptors.
Therefore low B12 can occur after a gastrectomy, gastric atrophy, or when the body produces antibodies to parietal cells and intrinsic factor. This autoimmune condition (known as Pernicious anaemia has a peak at around 60 years, is familial and increases the risk of stomach cancer in males).
Another main cause of B12 malabsorption is small bowel disease. This can include Crohns or coeliac disease or bowel infections (tapeworm).
Measure vitamin B12 (will be low)
Neuro examination will reveal absent reflexes.
Check levels of B12 intrinsic factor.
Antibodies for coeliac disease
Drink lots of radioactive B12
Measure the excretion of B12 in the urine.
If there is no B12 in the urine repeat the test with intrinsic factor.
Bilateral peripheral neuropathy (loss of peripheral vision)
Subacute combined degeneration of the cord
Posterior and pyramidal tracts of the spinal cord are degraded
Optic atrophy (retinal tissue destroyed)
Haematology 3 Haemoglobin and Thalassaemia
1. Name the key components of haemoglobin
2. Name 3 types of haemoglobin
3. Describe the oxygen dissociation curve
a) state what each axis represents
b) explain the shape
c) name 3 factors which affect it
4. Understand relationship between globin genes and different types of haemoglobin
5. Explain how genetic defects in globin genes lead to thalassaemia
6. Describe clinical and haematolog