Microcytic Anaemia Flashcards
Haematology : RBC production
1. Erythropoetin
* a hormone produced by the kidneys in response to cellular hypoxia
2. Bone marrow
* Erythropoetin bind on the erythropoietin receptors on the immature blood cells causes them to mature
* Immature (Proerythroblast) —-> mature (Erythrocytes)
Haematology : Components of Erythrocyte
1 . Haem molecule x 4
Components;
* Protoporphyrin
* Iron
2 . Globin (polypeptide)
Made up two main types of globin molecules;
* Alpha Globin x2
* Beta Globin x2
Haemoglobin - components
4x haem groups in a single haemoglobin molecule
Each Haem group Consist of;
1. Iron (Fe2+) - site of O2 molecule binding
2. Porphyrin ring (Bound to Iron)
-
Globin chains - protein subunits that make up the backbone of the haemoglobin molecule
* HbA (Adult Haemoglobin)
* 2x Alpha Globin
* 2x Beta Globin chain
structural integrity of hemoglobin and contribute to its ability to undergo conformational changes during oxygen binding
Microcytic anaemia : Causes
microcytic anaemia is “TAILS”:
* T – Thalassaemia
* A – Anaemia of chronic disease
* I – IRon deficiency anaemia
* L – Lead poisoning
* S – Sideroblastic anaemia
Iron deficiency anaemia : Pathophysiology
- Reduced Iron stores
-
Impaired Haem synthesis
* Iron is a critical component of the heme group,
* insufficient iron availability impairs the synthesis of heme.
3 . Decreased Hemoglobin Production:
shortage of heme results in decreased hemoglobin production within the developing red blood cells.
4 . Microcytic Red Blood Cells:
* Inadequate haem results in microcytic RBC in bone marrow
* hypochromic - reduced hemoglobin content.
5 . Decreased Oxygen-Carrying Capacity:
Iron deficiency anaemia : Causes
- Decrease in RBC due to insufficient iron stores
Causes of IDE
1. Inadequate Iron Intake
2. Impaired Iron Absorption
3. Chronic Blood Loss:
Iron deficiency anaemia - Clinical features
- Decreases oxygen to tissues : Pallor, Fatigue, palpitations, tachypnea
- PICA : craving for non food substances
- Glossitis - smooth beefy red tongue
- Koilonychia - spoon shaped, concave nails
Iron deficiency anaemia - Diagnosis
Lab results :
* Low MCV, low haemoglobin
% saturation low : % of iron occupying Transferrin
2 . TIBC increases :
* Measure of the maximum amount of iron that can be bound to transferrin - ability to bind and transport Iron
3 . Serum ferritin
* Reduction : Low iron stores
* Increase : Iron overload / Inflammation
(less iron, less iron occupying transferrin), low Ferritin, TIBC increases (to compensate for the low iron)
Iron deficiency anaemia - Mx
1 . Medication - PO iron supplement
2 . Increase dietary iron
* Vitamin C increases absorption of iron, avoid calcium can decrease iron absorption
3 . Avoid transfusion except in acute cases
* Lack of iron, unable to maintain Hb levels
Anaemia of Chronic disease- Pathophysiology
1 . Hepcidin - protein produced by Liver
* Blocks absorption of iron in duodenum
* Reduces Iron levels in the blood
2 . Inflammation - increases Hepicidin level
* Avoids Iron used for bacterial nutrient
3 . Reduced iron levels
* Chronic inflammation reduces serum iron levels
Anaemia of Chronic disease- Diagnosis
Lab results:
1 . Low serum Iron
2 . Low transferrin saturation %
3 . Low total iron binding capacity -
* decreases production of transferrin to reduce iron in the blood stream
4 . High Ferritin
* increases storage of iron
Anaemia of Chronic disease - Mx
Anaemia of chronic disease often occurs with;
* Chronic kidney disease due to reduced production of erythropoietin by the kidneys
* the hormone responsible for stimulating red blood cell production. Treatment is with erythropoietin.
Haemoglobin - Globin chain component
Haemoglobin - Globin chain component
Hemoglobin consists of four globin chains: two alpha (α) and two beta (β) chains in adults.
* Alpha globin chains are encoded by four genes (two on each chromosome 16),
* Beta globin chains are encoded by two genes (one on each chromosome 11).
Alpha thalassaemia : Definition
Deletion or Mutation of Alpha Globin Genes:
1. Alpha thalassemia results from the deletion or mutation of one or more alpha globin genes.
2. The severity of the condition depends on the number of affected genes.
Alpha thalassemia : Types
1 . Silent Carrier:
* One alpha globin gene is affected (usually due to deletion)
* no clinical symptoms.
2 . Alpha Thalassemia Trait:
2. Two alpha globin genes are affected,
* Clinical symptoms : Mild anemia.
Individuals are usually asymptomatic or have minimal symptoms.
3 .Hemoglobin H Disease:
1. Three alpha globin genes are affected
* Clinical symptoms : moderate to severe anemia.
* Hemoglobin H (HbH) is formed, which is less stable and leads to red blood cell damage
4 .Hydrops Fetalis:
1. All four alpha globin genes are affected - complete absence of alpha globin chains
* Clinical symptoms : This condition is incompatible with life, and affected fetuses may not survive to term.
Beta Thalassemia : Definition
-
Mutation or Deletion of Beta Globin Genes:
* Beta thalassemia results from mutations or deletions in one or both beta globin genes.
* The severity of the condition depends on the number of affected genes and the specific genetic mutations.
Beta Thalassaemia Pathophysiology
-
Beta globin deficiency,
* Free alpha chains accumulate within the red blood cells
* Alpha chains clump together to form intracellular inclusions which damage the red blood cell’s cell membrane.
2 . This causes ; haemolysis
* Haemoglobin breakdown results in harm recycled into iron and unconjugated bilirubin
3 . Excess unconjugated Bilirubin and Iron
* Overtime, excess unconjugated bilirubin leads to jaundice and excess iron deposits leads to secondary haemochromatosis
4 . Haemloysis
* leads to anaemia which can cause hypoxia
Beta Thalassemia : Types
1 . Beta Thalassemia Trait:
1x mutated gene + 1x normal gene
One beta globin gene is affected
* Clinical sx : mild anemia.
* Mild hypochromia, microcytic anaemia
* Microcytosis very low compared to Hb
* Individuals are usually carriers and may not exhibit significant symptoms.
2 . Beta Thalassemia Intermedia:
Two beta globin genes are affected - two mutated genes that code for reduced beta globin chain synthesis
* Clinical sx : moderate to severe anemia. Individuals may require occasional blood transfusions.
3 .Beta Thalassemia Major (Cooley’s Anemia):
Both beta globin genes are affected,
* Clinical sx : causing a severe form of anemia.
Individuals require regular and lifelong blood transfusions for survival.
Beta Thalassaemia : Inheritance
Beta globin chains are encoded by two genes (one on each chromosome 11).
* Gene : autosomal recessive, 2x mutated genes from each parent
Beta Thalassaemia : Clinical features
Clinical features; No sx until 3-6 months of life as haemoglobin is still produced
1. Anaemia, shortness of breathlessness
1. Jaundice
1. Hepatosplenomegaly
1. Iron overload - haemochromatosis
1. Facial features : enlarged forehead, cheek bones
Beta Thalassaemia : Diagnosis
Peripheral blood smear :
* Microcytic, Hypo-chromic red blood cells,
* Target cells (small red blood cells that look likes bullseyes due to scrunching up of the excess cell membrane)
Haemoglobin electrophoresis : low HbA (low adult haemoglobin) , increased HbF and HbA2 (two alpha, two delta chains)
XR - Skull bones show radiotransluscent bone marrow with fine hair like projections
Beta Thalassaemia :Management
Repeated transfusion - leads to iron overloads, organ failure
Iron chelation therapy e.g. desferrioxamine
Thalassaemia : Blood film
- Hypochromic, Microcytic
- Decreased synthesis of normal hemoglobin contribute to decreased RBC survival
- increased destruction (hemolysis).
- Bone marrow compensation : upregulate RBC production, however
these RBCs are smaller (microcytic) and have a reduced hemoglobin content (hypochromic)
Thalassaemia : HbH
Seen in Alpha Thalassaemia
- Hemoglobin H disease - remaining alpha globin chain forms unstable tetramers (HbH), leading to moderate to severe hemolytic anemia.
- Characteristics: HbH is less stable than normal hemoglobin, leading to increased destruction of red blood cells and contributing to the anemia seen in Hemoglobin H disease.
Sideroblastic anaemia : Definition
Sideroblastic anemia is a type of anemia;
* characterized by the presence of ringed sideroblasts in the bone marrow.
- These are erythroblasts containing iron-loaded mitochondria encircling the nucleus
- Blood disorder where there is a build up of iron in the RBCs in the body causing them to be immature and dysfunctional
Sideroblastic anaemia : Pathophysiology
Sideroblastic aaemia -
1 . Defective protoporphyrin synthesis - impaired incorporation of iron to form haem.
* Vitamin B 6 deficiency - cofactor for enzyme in haem synthesis
2 . Deposits of iron in the mitochondria
* firm a ring around the nucleus called a ring sideroblast.
3 . Defective RBC undergo apoptosis
* within bone marrow and fewer functional RBC in circulation leading to Anaemia
Sideroblastic anaemia : Causes
Congential -
* X linked form of delta-aminolevulinate synthase-2 deficiency
* which means it occurs on the X chromosome and affects mainly boys
* Mutation in gene affecting mitochondrial function
Acquired causes :
1. Myelodysplastic syndrome } abnormalities in morphology and maturation of RBCs
Interfence with vitamin B6 metabolism, iron, folate deficiency or damage to mitochondrial function
1 . Excessive alcohol use -
* leads to mitochondrial damage and nutritional deficiencies such as Vitamin B6, iron and folate which affects the mitochondria’s ability to form haem.
2 . Drugs : Anti-TB medication such as isoniazid
Lead poisoning
Sideroblastic anaemia : Clinical features
- Anaemia - fatigue, dyspnea, palpitations, pallor
- Erythropoietic haemochromatosis - hepatosplenomegaly, cardiac arrhythmia
Sideroblastic anaemia :Diagnosis
1 . Bone marrow aspirate smear -
* presence of sideroblasts confirm diagnosis
* Prussian blue stain reveals iron ring around the nucleus
2 . Iron studies; High ferritin, high iron, high transferritin
* Acquired sideroblastic anaemia - macrocytic anaemia
* Heridatry sideroblastic anaemia - hypochromic microcytic anaemia
3 . Blood film : Basophilic stippling of red blood cells
basophilic stippling is attributed to the presence of aggregates of ribosomal RNA (rRNA) in the cytoplasm of red blood cells.
Sideroblastic anaemia :Management
Pyridine (Vitamin B6) , folic acid and thiamine } replacement
Lead poisoning anaemia : defintion
Lead exposure, absorbed into the bloodstream interferes with the synthesis of heme in the bone marrow
1 . Distrupts Protoporphyrin production in bone marrow
* Component of haem
* Heme synthesis is impaired due to the inhibition of enzymes such as ferrochelatase and aminolevulinic acid dehydratase (ALA-D).
2 .Microcytic and Hypochromic Anemia:
The disruption in heme synthesis leads to the production of
* abnormally small red blood cells (microcytic) with reduced hemoglobin content (hypochromic).
3 .Basophilic Stippling:
* Lead poisoning may cause basophilic stippling in red blood cells.
* Basophilic stippling refers to the presence of dark-staining granules in red blood cells, indicating abnormal aggregation of ribosomal RNA.
Lead poisoning : RF
Risk factors;
* Water contamination/lead pipes
* Exposure to leaded paint/toxins in industry
Lead poisoning : Clinical features
- Anaemia - pallor, fatigue, dyspnea
- Lead toxicity : abdominal pain, headache, muscle/joint pain, confusion and ataxia
Lead poisoning :Diagnosis
Lab results : Dx via raised blood lead levels
* Microcytic anaemia
* Raised serum/urine delta aminolaevulinic acid
Blood film : hypochromic microcytic anaemia, basophilic stippling
Lead poisoning :Management
Chelation therapy : Dimercaptosuccinic acid (DMSA)
