Case 14 Flashcards
What is haematopoesis?
Process of how body creates blood cells
What are erythrocytes?
Red blood cells
Structure of erythrocytes?
Small, flexible , bioconcave discs, no nucleus, high haemoglobin conc
What are leukocytes?
White blood cells
What are thrombocytes?
Platelets
Structure of thrombocytes?
(Platelets)Small disc shaped fragments without a nucleus
Function of thrombocytes?
(Platelets) Bloodclot formation, aid vasoconstriction, aid in wound healing, part of immune response, part of angiogenesis (formation and growth of new blood vessels)
What is the composition of blood?
55% Plasma, 1% Leukocytes (wbc) and Thrombocytes (platelets) , 45% Erythrocytes (rbc)
Lifespan of platelets?
9/10 days
Lifespan of erythrocytes?
(RBCs) 120 days
Lifespan of leukocytes?
(WBCs) a few days - a few years
What are the 3 layers of blood (when separated by centrifugation) and what are their percentages of the total?
Plasma 55%, Buffy coat <1% and Red blood cells 45%
What is contained in plasma?
Clotting factors
What is contained in buffy coat?
White blood cells (leukocytes) and platelets
Site of Haematopoesis in 0-2 month fetus?
Yolk sac
Site of Haematopoesis in 2-7 month fetus?
Liver, spleen
Site of Haematopoesis in 5-9 month fetus?
Bone marrow
Site of haematopoesis in infant?
Bone marrow of practically all bones
Site of haematopoesis in adult?
Bone marrow of: vertebrae, ribs, sternum, skull, sacrum and pelvis, proximal end of femur
Composition of bone marrow at birth?
100% Red
Composition of bone marrow of adults?
50% red 50% yellow
What is contained in yellow bone marrow?
Fat cells & stromal cells and stromal matrix
What are stromal cells?
Many different types of cell which support and regulate production of blood cells in bone marrow
What is stromal matrix?
A specialised extra cellular matrix in bone marrow containing proteins and other molecules to support Haematopoesis
What is erythropoesis?
Production of red blood cells
Describe process of erythropoesis?
1)Haematopoetic stem cells
2)become Erythroid progenitor cells
3)become Erythroblasts
4)Erythroblasts start producing haemoglobin and start maturing
5)become normoblasts
6)Late normoblasts have nucleus exrtuded
7)become reticulocytes (immature RBCs)
6)become erythrocytes (mature RBCs)
What is thrombopoesis?
Production of platelets
Process of thrombopoesis?
1)Haematopoetic stem cells
2)Become megakaryocytes
3)Undergo endomitosis - chromosomes replicate but nucleus doesn’t so cell gets very big
4)Proplatelets (which are small protrusions) form in cytoplasm of megakaryocytes
5)Proplatelets extend out into blood vessels in bone marrow
6)Proplatelets fragment into platelets
What are leukocytes?
White blood cells
What are the 2 main groups of leukocyte?
Granulocytes and Agranulocytes
3 examples of types of granulocytes?
Neutrophils, Eosinophils, Basophils (types of white blood cells)
What are the 2 types of agranulocytes?
Lymphocytes and Monocytes
What is granulopoesis?
Production of granulocytes (type of white blood cell)
Process of granulopoesis?
1)Haematopoetic stem cells
2)Become myeloid progenitor cells
3)become myeloblasts
4)become promyelocytes
5)become myelocytes
6)become band cells
7)mature band cells released into blood stream and migrate into different tissues
8)band cells differentiate into tissue-resident-granulocytes
(Either neutrophils/eosinophils/basophils)
What is lymphopoeisis?
Production of lymphocytes (types of white blood cell)
2 examples of lymphocytes?
T cells and B cells
Process of T cell lymphopoesis?
1)Haemopoetic stem cells
2)become lymphoid progenitor cells
3)LPCs move to thymus
4)become thymocytes
5)mature to become T cells
Process of B cell lymphopoesis?
1)Haemopoetic stem cells
2)become lymphoid progenitor cells
3)LPCs move to bone marrow
4)become Pre B cells
5)become B cells
What is monopoesis?
Production of monocytes (type of white blood cell)
Process of monopoesis?
1)Haematopoetic stem cells
2)become myeloid progenitor cells
3)become monoblasts
4)become promonocytes
5)become monocytes
What are transcription factors?
Proteins which regulate rate of transcription by binding to DNA sequences and activating and repressing gene expression
What are growth factors?
Regulate cell growth, proliferation, differentiation and survival by binding to specific receptor on surface of target cells
Which hormone regulates red blood cell production, and when is it produced and where?
Erythopoietin, produced by kidney in response to low oxygen levels
Antigens present on red blood cells of blood group A?
A
Antibodies present in plasma of blood group A?
Anti-B
Antigens present on red blood cells of blood group B?
B
Antigens present in plasma of blood group B?
B
Antigens present in plasma of blood group B?
Anti-A
Antigens present on red blood cells of blood group AB?
A and B
Antibodies present in plasma of blood group AB?
None
Antigens present on red blood cells of blood group O?
None
Antibodies present in plasma of blood group O?
Anti A and anti B
What happens to blood once collected from donor?
Tested for infection then split via centrifugation into red blood cells, platelets and plasma which are packaged separately
Risks of blood transfusion?
Immune response to new blood
Transfusion-transmitted-infections
Transfusion related acute lung injury
Transfusion associated circulatory overload
Iron overload
Allergic reactions
What is Haemolysis?
Break down of red blood cells
Adverse effects of haemolysis on body?
Anaemia, Jaundice, Kidney damage
What is anaphylaxis?
Severe, life threatening allergic reaction
Adverse effects of anaphylaxis on body?
Hypotension (low bp), difficulty breathing, cardiac arrest
Adverse effects of iron overload on body?
Organ damage, deposition of iron in tissues (can cause damage and inflammation), cardiovascular complications
Examples of when a blood transfusion may be necessary?
Low haemoglobin levels (blood can’t carry much O2)
Severe anaemia (low iron)
Significant blood loss and bleeding (internal or external)
Bone marrow suppression (so can’t produce new blood cells)- eg due to cancer
Patients with inherited blood disorders
Severe infection or sepsis - blood needed to support organ function
What is a haemorrhage?
Excessive bleeding (external or internal)
What is sepsis?
Extreme immune response to infection - highly dangerous
How do they do compatibility testing between donor and recipient blood samples?
Determine blood type of both samples
A cross match test is performed, samples of donor and recipient blood is mixed to check for any agglutination (clumping) and haemolysis (red blood cell destruction)
Examples of infectious conditions which can be spread via blood transfusion?
Hepatitis B and C, HIV, Syphalis, Malaria, Bacterial infections
What are the measures taken to prevent transmission of infection through blood transfusion?
Donors are screened and medical history taken
Donor blood is tested in laboratory
Some blood samples undergo pathogen inactivation procedures to reduce risk
Leukocyte reduction filters used to remove leukocytes (WBCs) from donor blood (these can harbour infectious agents)
Components of donor blood are separated to allow for targeted transfusion therapy
What is the function of blood?
Distributes oxygen, nutrients, hormones, blood cells and platelets
Regulates body temp, pH, solute, restricts osmosis into tissues
Protects against fluid loss and against infection by contributing to inflammatory and immune response
What is haemoglobin?
Protein found in red blood cells that carries oxygen from lungs to tissues
Returns CO2 from tissues back to lungs
Describe structure of haemoglobin?
4 protein sub units each containing a haem group - which contains iron and binds to O2 molecules
What is anaemia?
Reduction in haemoglobin conc
Symptoms of anaemia?
Fatigue, weakness, reduced energy or exercise tolerance, shortness of breath, palpations, dizziness, irritable, impaired concentration
Physiology of anaemia?
Anaemia causes reduced amounts of O2 to be delivered to tissues and organs (leading to tissue hypoxia - O2 deficiency)
To compensate for this, the body increases cardiac output and peripheral vasodilation occurs.. these are in an attempt for more O2 to reach tissues
What causes fatigue, dizziness and cold intolerance often experienced with anaemia?
Reduced oxygen delivery causes these symptoms
What causes shortness of breath, tachycardia and palpitations often experienced with anaemia?
Increased respiration and heart rate in order to absorb more oxygen
What causes headaches often experienced with anaemia?
Cerebral vasodilation occurs to increase oxygen delivery
This causes increased pressure, which can cause headache
What causes Pale skin and mucous membranes often experienced with anaemia?
Low haemoglobin and oxygen levels
Causes of anaemia?
Not enough red blood cells produced
Defective red blood cells
Red blood cells lost or destroyed
3 different types of deficiencies which can cause anaemia?
Iron, Vitamin B12, Folate
What is macrocytic anaemia and what can it be caused by?
Red blood cells too large
Can be caused by vit B12 deficiency, folate deficiency, medications, liver diseases, bone marrow disorders
What is haemolytic anaemia and what can it be caused by?
Premature destruction of red blood cells (leading to a shortage)
Can be caused by inherited disorders (eg sickle cell and thalassemia), autoimmune disorders (body attacking red blood cells), some infections, toxins, medications, heart valve or blood vessel defects.
Three types of inherited anaemias?
Haemoglobin disorders - eg thalassemia or sickle cell
Membrane disorders - hereditary spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis
Enzyme disorders - G6PD deficiency, pyruvate kinase deficiency
What is thalassaemia?
Inherited blood disorder which causes abnormal haemoglobin by causing reduced production of one or more globin chains
What is alpha thalassaemia?
Reduction in number of alpha chains of haemoglobin
What is beta thalassaemia?
Reduction in number of beta chains of haemoglobin
Symptoms of thalassaemia?
Moderate to severe anaemia
Extramedullary Haematopoesis
Iron overload (which can cause complications and failure of heart, liver and endocrine organs)
What is Extramedullary haematopoesis?
Production of blood cells outside of bone marrow (as ability of bone marrow is impaired or there is increased demand for blood cells)
Function of spleen in erythrocyte (RBC) production?
In times of high demand the spleen can produce haematopoetic stem cells
Extramedullary haematopoesis can occur in spleen
During fetal development, spleen is a site of erythropoesis
What is sickle cell disease?
Inherited red blood cell disorder which causes presence of haemoglobin S, an abnormal haemoglobin
This causes RBCs to become sticky, rigid and crescent shaped
Signs and symptoms of sickle cell disease?
Sickle cell crises
Acute chest syndrome
Sepsis
Stroke
Chronic organ damage
What is acute chest syndrome?
Serious complication of sickle cell disease
Inflammation and blockage of blood vessels in lungs
Chest pain, breathing difficulty, fever and cough
What are sickle cell crises?
Blockage of small blood vessels leading to tissue ischaemia and pain
Why does sickle cell cause blockages?
Cells are rigid, sticky and crescent shaped so can get stuck in small blood vessels
What is polycythaemia?
Increased production of red blood cells
This can lead to thicker blood which can cause complications
What is leukopenia?
Decrease in number of white blood cells in blood
What is leukocytosis?
High number of white blood cells in blood
What is thrombocytosis?
High number of platelets in blood
What is thrombocytopenia?
Low level of platelets in blood
What is ductus arteriosus?
Connects pulmonary artery to aorta (for fetal circulation)
What is foreman ovale?
Hole between the 2 atria for fetal circulation
What is ductus venosus?
Blood vessel which connects umbilical vein (in umbilical cord) to inferior vena cava
Describe changes to the circulatory system at birth?
Ductus arteriosus closes
Foreman ovale closes
Increase in pulmonary blood flow as lungs begin to operate once baby is born
Ductus venosus closes
Most prevalent type of haemoglobin in adults?
Haemoglobin A
Structure of HbA?
2 alpha globin chains and 2 beta globin chains
What is HbA2?
2 alpha globin chains + 2 delta globin chains
Same function as HbA but les prevalent
What is HbF?
Fetal haemoglobin
Predominantly in fetuses and newborns and is gradually replaced by HbA
2 alpha globin chains and 2 gamma globin chains
Why do fetuses have HbF and not HbA?
HbF has a higher affinity for O2 than HbA
This helps facilitate O2 transfer across placenta from mother to fetus
What is HbS?
A genetically mutated variant of Hb
Associated with sickle cell disease
How can HbS cause sickle shaped red blood cells?
Under certain conditions, the HbS molecules can polymerise and this causes red blood cells to become rigid and sickle shaped
What is HbC?
A genetically mutated variant of Hb
Associated with HbC disease
What is HbC disease?
Red blood cells are more rigid and have a slightly different shape
This leads to mild haemolytic anaemia
Explain process of destruction of red blood cells?
1)Macrophages engulf unwanted RBCs
2)Haemoglobin broken down into haem and globin
3)Haem converted into biliverdin then bilirubin then excreted by liver as bile
4)Globin is converted into amino acids which are used in protein synthesis
5)Iron is either stored in liver as ferritin or transported to bone marrow for new Hb molecules
6)Other waste products are excreted
What is haemolytic disease of newborn?
When mother’s and fetus’ blood cells don’t match and cause mothers immune system to attack the baby’s red blood cells.
Commonly when mother is Rh-negative and baby is Rh-positive
What increases the risk of haemolytic disease of newborn?
Previous pregnancies or blood transfusion - as the mother has been exposed to the antigen and made antibodies against it
What increases the risk of haemolytic disease of newborn?
Previous pregnancies or blood transfusion - as the mother has been exposed to the antigen and made antibodies against it
What complications can haemolytic disease of newborns cause?
Jaundice and anaemia
What are preventative measures taken for haemolytic disease of newborns?
Screening during pregnancy
Treatment with Rh antibodies
What is immunoglobulin?
Antibodies
What is contained in red bone marrow
Haematopoetic tissue (used in haematopoesis )
