Haematology Flashcards
Haematopoeisis
Process through which all types of mature blood cells are produced
What do Erythroid / megakaryocytic lineage cells give rise to?
Red cells and platelets
What do granulocyte/ macrophage lineage give rise to?
Granulocytes and monocytes
What do lymphoid lineage give rise to?
T cells, B cells and NK cells
Primitive haematopoeisis
Started in yolk sac
Give rise to red blood cells
When is primitive haematopoeissi replaced by definitive haematopoiesis at?
5-6 weeks gestation
What is definitive haematopoiesis?
Produces all blood cell types
Where are definitive heamtopoietic stem cells created?
Develop in the aorta-gonad mesonephros region of the dorsal aorta
When do HSC’s migrate to AGM to fetal liver and spleen?
6-7 weeks gestation
Liver is then the primary site of haematopoiesis
What is main site of heamtopoiesis at 3rd trimester and at birth?
Bone marrow
Originally occurs in all areas of bone marrow - restricted to axial skeleton and proximal ends of long bones later
What does metal Hb consist of? When does it start getting produced in gestation?
2 alpha chains, 2 gamma chains
Produced from 3-4 weeks of fatal life
What does the binding and releasing of oxygen cause?
Causes small configuration of globin chains in Hb molecule
Oxygen is unloaded, Hb molecule opens up allowing 2,3-diphosphoglcyerate (2-3 DPG) to enter reducing oxygen affinity and ensuring Hb molecule does not take up oxygen from tissues
What is average life span of RBC?
120 days in older children and adults
90 days in neonates
Iron absorption
Iron in diet is absorbed by enterocytes in duodenum either in Fe2+ form or as haem
Ferroportin, iron transporter protein, transports iron across basolatereal membrane of enterocyte into the blood stream
Iron binds to transferrin and transported to tissues
Transferrin
Transferrin can bind to 2 molecules of iron and deliver this to cells that express transferrin receptors
Ferritin
Storage of iron
Shows total body iron levels (in absence of inflammation)
Why are Hb values higher in utero? What are the values?
Higher oxygen affinity of HbF and fall during first few months of life
Neonate - <130
1-12 months <100
1- 12 years <110
Causes of Reduced MCV - microcytosis
Iron deficiency
Thalassaemia major or thalassaemia trait
Anaemia of chronic disease
Causes of increased MCV - macrocytosis
Folate deficiency
Vit B12 deficiency
Diamond-Blackfan anemia
Liver Disease
Hypothroidism
Diamon-Blackfan Aneamia
Genetic disorder
Presents with anaemia at birth or during infancy
50% physical abnormalaties - craniofacial abnormalities, thumb and growth restrictions
Autosomal dominant
Mutations in ribosomal protein genes - RPS19
Bone marrow biopsy
Treatment - steroids and regular blood transfusions
Transient erythroblastopenia
Parvovirus-induced red cell aplasia
TEC - presents 2 year olds
Transient red cell aplasia triggered by unknown infective agent
Recovery occurs spontaneously within 4-8 weeks
Normocytic with neutropenia
Blood tests for Haemolytic Anaemia
Reduced Hb
Raised reticulocytes - immature red blood cells
Raised unconjugated bilirubin
Raised LDH
Intravascular haemolysis
Occur in circulation
Depletion of haptoglobin
Increase LDH
Large numbers of fragmented RBCs (schisocytes)
Extravascular haemolysis
Takes place in spleen or liver - can occur in lung
Spleen or liver macrophage Fc receptors bind immunoglobulin attached to RBC
Inherited haemolytic disorders
Red cell membrane defects - hereditary spherocytosis, hereditary ellipocytosis
Red cell enzyme defects - G6PD deficiency and pyruvate kinase deficiency
Haemoglobinopathies - sickle cell disorders, thalassaemias
Acquired Haemolytic disorders
Autoimmune - idiopathic, SLE, JIA
Microangiopathic - HUS, TTP, haemangiomas
Infection - Malaria, septicaemia
Other - burns, lead poisoning
What conditions cause Positive DAT’s
Haemolytic disease of newborn
Autoimmune haemolytic anaemia
Drug-induced anaemia
Haemolytic transfusion reactions
Red cell enzyme defects
Glucose-6-phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
What does G6PD do?
Protects cell from oxidative damage
Catalyses first step of pentose phosphate pathway
How is G6PD deficiency inherited?
X-linked disorder
What causes an acute haemolytic crisis in G6PD deficiency
Infection
Medications - co-trimoxazole, dapsone, nitrofurantoin, chloramphenicol, chloroquine, aspirin
Blood results in acute haemolytic crisis
Reduced Hb
Raised reticulocytes
Hyperbilibuinaemia
Increased LDH
Blood film in G6PD deficiency
fragmented red cells ‘bite’ cells and polychromasia
Heinz bodies (denatured hB)
Not in crises - blood film normal
Pyruvate kinase deficiency
Results in sufficient ATP production
Causes rigid cells and haemolysis
How is pyruvate kinase deficiency inherited?
Autosomal recessive
Pyruvate kinase deficiency blood film
Prickle red cells
Autoimmune haemolytic anaemia - what it is and types
Produce antibody against their own red cells
Types - warm and cold (depends if antibody binds most strongly at 37 degrees or 4 degrees)
Warm AIHA
usually IgG antibodies
Cold AIHA
usually IgM antibodies