Anaemia Flashcards
what factors can affect normal range of Hb (5)
- Gender
- Pregnancy
- Extremes of age
- Different labs / testing platforms
- Altitude
what are the 3 layers of blood that would appear in a centrifuged tube (or if left for a long time to separate
-
Light Yellow Layer – plasma [55% of total volume]
- It contains Plasma proteins, electrolytes, hormones and nutrients
- 91% of this layer is made up of water
-
Yellow/Brown Layer - Buffy coat
- Contains cells of immune system → Platelets and white cells
-
Red Layer
- It contains red Cells
describe the structure of erythrocytes & their function
- Biconcave structure
- No nucleus
- Function: O2 and CO2 transport
what gives erythrocytes their red colour
The red colour comes from an iron-containing oxygen transport metalloprotein called haemoglobin
define erythropoiesis
Production of red blood cells.
describe the process of erythropoiesis
- Red cells come from the bone marrow.
- They start of as precursor cell called Pronomoblast.
- They then differentiate through a lineage of different cells, extrude their nucleus, and eventually become erythrocytes (RBC)
- Reticulocyte are the penultimate cells in the lineage. They have an extruded nucleus but still have RNA so can still make haemoglobin (not possible in erythrocyte
what can more reticulocytes in blood indicate
- During bleeding or haemolysis, the bone marrow is stimulated to release red cells, often earlier progenitors released such are reticulocytes are also released into the blood. This is known as reticulocytosis.
- Therefore more reticulocytes in blood indicates some red cell have been lost.
where are red blood cells made
bone marrow
describe the structure of haemoglobin
- Hb made up of 4 polypeptide chains (tetramer)
- There is 1 x Heme molecule per chain which allows for the binding of 1 O2 ⇒ 4 binding sites for O2 per Hb molecule.
what does the oxygen dissociation curve show
The oxygen dissociation curve illustrates how RBCs carry and release oxygen.
what factors can affect haemoglobin affinity for oxygen (5)
- temperature
- pH
- CO2 levels
- 2,3-DPG
- Hb type
what can cause a left shift to oxygen dissociation curve (6)
- body area (placenta vs lungs)
- higher oxygen affinity
- high pH (decrease H+)
- low CO2 levels
- low temperature
- low 2,3-DPG
what can a decrease in red blood cells lead to
- A decrease in red cells results in permanent reduction in amount of O2 that can reach tissues ⇒ symptoms of anaemia.
- If you have a decreased number of red cells or inability to release O2 from red cells you are more likely to lack O2 to tissues and as a result you will feel tired.
define anaemia
Reduction in haemoglobin (Hb)
what are the symptoms of anaemia (4)
- Fatigue
- Breathlessness on exertion
- Palpitations
- Angina
what are the (clinical?) signs of anaemia
- Pallor (in context of skin colour)
- Tachycardia
- Signs of heart failure
- Bounding pulse
- Flow murmur through heart
- Koilonychia (spooning of nails) [1]
- Angular stomatitis (soreness at side of mouth) [2]
what do clinical features of anaemia depend on
- Hb level (how low/high)
- Time taken for Hb to fall
- Cause of anaemia
- Other organ reserve e.g. lungs, heart (if you have respiratory problems or heart problems your ability to tolerate anaemia is less
where is the best place to assess for pallor & what do you need to think about when assessing
- Best places to look for pallor is conjunctiva.
- When assessing pallor you need to think about skin tone of patient.
what are some causes of anaemia (3)
- Reduced production of red cells
- Increased Destruction of red cells
- Poor function of red cells
what can cause reduced production of red blood cells (4
- deficiencies in iron, B12 and folate
- bone marrow pathology
- displacement in bone marrow (egg leukaemia, cancer, myelofibrosis)
- chronic disease (multi-factorial): renal failure, myeloma, chronic inflammatory conditions
what can cause iron deficiency (3
- Lack of Iron in diet
- Malabsorption of Iron
- Chronic blood loss (heavy periods)
what can cause B12 & folate deficiency (3) 🟤🟣
- High Alcohol intake
- Lack of B12 & folate in diet
- Increased cell turn over: cells use up the body reserves of B12 and folate
what is pernicious anaemia
problems with gastric parietal cells and production IF means you can’t absorb B12 and folate.
what is aplastic anaemia
don’t produce enough cells in bone marrow
what is myelodysplasia
- dysregulation of cell production
what can cause increased destruction of RBC (3)
- Haemolysis (break down of red blood cells)
- Large spleen
- Bleeding
what can cause haemolysis (2)
- Immune causes of haemolysis → autoimmune disease produce antibodies against red blood cells
- Non-immune causes of haemolysis, e.g. drugs
how does a large spleen cause increased destruction of RBC
- The spleen has function in clearing dead/abnormal cells from blood via splenic macrophages.
- If red cells don’t look normal (e.g. sickle cell disease) your spleen may take out red cells from circulation at higher rate.
- Also, if you have large spleen you have greater ability to take out red cells
what can cause poor function of RBC 🟣
- Poor function of red cells is mostly due to congenital problems (but also haemolysis)
- RBC Membrane defect
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Haemoglobin defect (haemoglobinopathy)
- Sickle cell anaemia
- Thalassaemia
- RBC Enzyme defect
- G6PD deficiency
- Pyruvate kinase deficiency
what are some important nutrients to ensure healthy RBC (3)
-
Iron
- Essential for haemoglobin production
-
Folate and B12
- Folate is needed to turn uracil into thymidine, an essential building block of DNA. B12 is involved in this process.
- This is why if you have increased cell turnover you use up more folate and B12.
- More than 95 % of folate in the body is in the red blood cells.
- Producing excess red cells e.g. in haemolysis, can result in folate deficiency
what are haemoglobinopathies & what are some examples
- Haemoglobinopathies area group of conditions affecting the haemoglobin component of blood.
- Examples:
- Hereditary spherocytosis
- Thalassaemia
- Sickle Cell Anaemia
- G6PD deficiency “favism”
how can GI problems cause anaemia
- Any inflammation or dysfunction of stomach, duodenum, liver, small or large bowel can cause malabsorption and problems with iron, B12 and folate uptake and therefore cause a microcytic/macrocytic anaemia (see below)
- Eg: Gastritis / colitis
- Pernicious anaemia / Coeliac disease
- Gastrectomy / colectomy
what is hereditary spherocytosis (describe the mechanism)
It is an Autosomal dominant inherited disease which causes anaemia.
- Mechanism:
- It is a defect in the red blood cell cytoskeleton
- It causes the RBC to contract to a sphere
- This allows for most efficient surface tension but the least flexible configuration – so the red cell gets damaged easily
- Damaged cells get removed by macrophages in the spleen → results in reduction of red cells → anaemia
what usually causes hereditary spherocytosis
Many different proteins can be affected to cause HS (usually caused by spectrin deficiency)
so spectrin deficiency affects many different proteins, this leads to HS
what is the treatment for hereditary spherocytosis (3)
- Folic acid (to combat folate deficiency)
- Splenectomy (remove spleen to reduce cell destruction)
- Rarely transfusion (if Hb is very low)
how might symptoms of hereditary spheocytosis exacerbated
Symptoms are exacerbated by inter-current illness (puts system under pressure as body requires more O2 and red cells aren’t able to step up)
what is Thalassaemia
- Mostly autosomal recessive.
- Common in South Mediterranean, north Africa, middle east and SE asia individuals.
describe the mechanism of Thalassaemia
- Caused by a defect in alpha or beta globin gene
- This results in an abnormal form of haemoglobin
- Red cells are destroyed by splenic macrophages results in reduction of red cells → anaemia
what does the severity of Thalassaemia depend on
- depends on how many of the alpha or beta globin genes missing:
- If you have only 1 gene missing = thalassaemia minor/trait parent.
- If you have a child that inherits the minor variant from both parents, they run the risk of getting both abnormal Hb genes resulting in large defect in HB and ability to carry O2. This is called thalassemia major.
- 1.5% of the global population (80 - 90 million people) are β-thalassemia carriers
what are some features of Thalassaemia
- Anaemia, dark urine (due to HB break down products), jaundice
- Splenomegaly
- Treatment varies from none to transfusion dependent (depends on minor (trait) or major)
what is sickle cell anaemia
- Autosomal recessive disorder
- Trait (1 gene) is asymptomatic
- High prevalence west / north Africa
describe the mechanism of sickle cell anaemia
- Defect of Hb beta globin gene results in Glutamic acid → valine switch
- This changes shape of Hb from bi concave disc to sickle like
- This shape is not as efficient at carrying O2 and more likely to be damaged (removed by spleen)
- Their shape also means they squash through capillaries where gas exchange occurs resulting in Obstructed capillaries → painful crises & end organ damage (due to blood supply obstruction)
what is hyposplenism
small spleen
sickle cell anaemia can cause hyposplenism
spleen is initially enlarged due to excessive red cell entrapment. Spleen atrophy and degeneration is noted in advanced disease.
what are the treatments for SCA (2)
- Exchange transfusion (red cell transfusion)
- Hydroxycarbamide (medication)
what is G6PD deficiency
It is X linked.
It iswhen the body doesn’t have enough of an enzyme called G6PD (glucose-6-phosphatedehydrogenase). This enzyme helps red blood cells work properly.
- Diagnosed in early life – cause of neonatal haemolytic anaemia
- The cells are sensitive to stresses e.g. infections or drug induced haemolysis.
describe the mechanism for G6PD deficiency
- Metabolic disorder → Glucose-6-phosphate dehydrogenase reduction.
- This is an Important enzyme in pentose phosphate shunt
- The enzyme maintains reduced NADPH which is the RBC only source of glutathione which mops up free radicals.
- Deficiency means Red cells unable to tolerate oxidative stress due to too many oxygen free radicals.
- Total deficiency is incompatible with life
what to do when investigating anaemia (6)
- Take a Full history
- Examination: look for signs of anemia and signs of underlying disorders
- Do a Full blood count and film (see amount of HB, and structure of cells – e.g. abnormal shape)
- Measure levels of Ferritin, B12 and folate
- Biochemistry: look at liver and kidney function (evidence of haemolysis e.g. increase in bilirubin)
- Haemolysis screen – e.g. cell turnover
what are the 6 full blood count terms★
- Haemoglobin
- Concentration of Hb in blood
- Haematocrit (automated) or Packed cell volume -PCV (centrifugation)
- Ratio of volume of red blood cells to the total volume of blood.
- Red blood count (RBC)
- How many red cells you have.
- NB: how dilute you are affects haematocrit but not RBC count.
- Mean cell volume (MCV)
- Calculated by PCV/RBC
- Gives average red blood cell size → helps in differential diagnosis
- Mean corpuscular haemoglobin (MCH)
- Calculated by Hb/RBC
- Tells us the amount of haemoglobin per red blood cell (affect colour of cell)
- Mean corpuscular haemoglobin concentration (MCHC)
- Calculated by Hb/PCV
- Tells us the amount of haemoglobin relative to the size of the cell
how are Hb and MCV used to diagnose cause of anaemia
- (ITS CBA BAE)
- A Low MCV indicates a microcytic anemia.
- Microcytic anemia is a type of anemia in which red blood cells are smaller than usual.
- It is usually caused by a problem with the production of red blood cells:
- Iron deficiency
- Thalassemia
- Sickle cell disease
- NB: If HB is very low → Chronically progressive microcytic anaemia
- Cause: blood loss via e.g. gastric ulcer/ gastric cancer
- A normal MCV indicates a Normocytic Anaemia.
- There is no problem with production of red blood cells but something else is causing the anemia:
- Chronic Disease
- Bone marrow failure
- Acute Blood loss
- There is no problem with production of red blood cells but something else is causing the anemia:
- A High MCV indicates a Macrocytic anaemia
- Cause:
- B12 & folate deficiency
- Haemolytic Anaemia (red cells destroyed faster than they are made)
- Excess alcohol consumption
- Cause:
