7. Anaemia Flashcards
Define the term anaemia and the factors that can affect the range value
The term anemia refers to a haemoglobin concentration lower than the normal range.
Normal range will vary with age, sex and ethnicity.
Importantly, anaemia isn’t a diagnosis, it is a manifestation of an underlying disease
Give the respective signs and symptoms of anaemia
As haemoglobin carries O2 in blood, the signs and symptoms will be related to the insufficient delivery of oxygen to tissues. Symptoms: 1. Shortness of breath 2. Palpitations 3. Headaches 4. Claudication (pain in limbs at rest) 5. Angina (pain in the chest due to an inadequate blood supply to the heart ) 6. Weakness & Lethargy 7. Confusion
Signs:
- Pallor
- Tachycardia
- Systolic flow murmur (heart mummurs heard during systole)
- Tachypnoea (increased respiratory rate to try and compensate for low oxygen levels)
- Hypotensio
Give the 4 specific signs that can help identify the CAUSE of anaemia
• Koilonychia - (Spoon shaped nails) - Iron deficiency • Glossitis - (inflammation & depapillation of tongue) - Vitamin B12 deficiency • Angular stomatitis - (Inflammation of corners of the mouth) - Iron deficiency • Abnormal facial bone development - Rare in recent times as preventable with early diagnosis - Thalassaemia
What can cause abnormal facial bone development?
Thalassaemia - increase of Haemopoiesis in areas we wouldn’t normally see an increase
Why might symptoms of anaemia be mild if it develops over time?
Body has had time to adjust to the lower concentration of Hb by increasing cardiac stroke volume to increase blood supply to tissues and increasing the conc of 2,3- Bisphosphoglycerate in RBCs to promote oxygen dissociation
Give the 3 main categories of problems that can cause anaemia to develop
- Problem in the bone marrow
- There’s reduced or dysfunctional erythropoiesis
- Abnormal haem synthesis
- Abnormal globin chain synthesis
(This means that a proper haemoglobin molecule isn’t being formed) - Problems with the RBCs
- Abnormal structure of the RBCs
(E.g the membrane structure is not right)
- Mechanical damage to the RBCs
- Abnormal metabolism of the RBCs - Excessive bleeding
E.g because if bowel cancer which causes an increase in blood loss meaning you’ll have lower levels of haemoglobin present - Increased removal by reticuloendothelial system
E.g by the spleen or liver
What is the role of erythropoietin?
It’s a hormone that’s produced and released by the pericytes in kidney when there are low levels of oxygen.
It’s used to trigger an increase in the synthesis and release of RBCs in the bone marrow by binding to receptord on erythroblasts in bone marrow
This leads to high blood oxygen so negatively feeds back to the kidney to reduce the release of erythropoietin.
Discuss how reduced or dysfunctional erythropoiesis might develop anaemia
• Anaemia can result from lack of response in the haemostatic loop e.g. in chronic kidney disease the kidney stops making erythropoietin
• Anaemia can result from marrow being unable to respond to EPO e.g. after chemotherapy, toxic insult or parvovirus infection
• If marrow is infiltrated by cancer cells or fibrous tissue (myelofibrosis) the number of normal haemopoietic cells is reduced
• In Anaemia of chronic disease e.g. in rheumatoid arthritis, iron is not made
available to marrow for rbc production
• In rare forms of blood cancer called myelodysplastic syndromes abnormal clones of marrow stem cells limit the capacity to make both red and white blood cells
Why might defects in Hb synthesis come about?
- Defects in the haem synthetic pathway can lead to Sideroblastic anaemia
- An insufficient level of iron in the diet can lead to iron deficiency anaemia (this is because not enough iron is present to make Haem)
- Anaemia of chronic disease can result in a functional iron deficiency (there’s sufficient amount of iron in the body but it’s not made available for erythropoiesis).
Give the examples of diseases caused by mutations in the genes encoding the globin chain proteins
- α Thalassaemia
- β Thalassaemia
- Sickle cell disease
Why might abnormal structure and mechanical damage to RBCs come about that is inherited? What does this cause?
- mutations in genes coding for the proteins involved in interactions between the plasma membrane and cytoskeleton
- causes cells to become LESS flexible and more susceptible to damage.
- RBCs are broken up in the circulation or removed more quickly by the RES
E.g. hereditary spherocytosis
Why might abnormal structure and mechanical damage to RBCs come about that is acquired? What does this cause?
- mechanical damage: shear stress as cells pass through defective heart valve e.g. MAHA in aortic valve stenosis
- cells snagging on fibrin strands in small vessels where increased activation of clotting cascade has occurred e.g. in disseminated intravascular coagulation
- heat damage from severe burns
- osmotic damage - drowning in freshwater
What type of anaemia does abnormal structure and mechanical damage to RBCs result in?
abnormal structure and mechanical damage to RBCs causes haemolytical anaemias. Microangiopathic haemolytic anaemias are caused by the mechanical damage aspect
What are schistocytes?
- Fragments resulting from mechanical damage to RBCs
* The presence of schistocytes is agood indicator that some form of pathology is present
Why does G6PDH deficiency cause defects in RBC metabolism?
• decrease in G6PDH activity limits amount of NADPH which is required for the reduction of oxidised GSSG back —> reduced glutathione (GSH).
• Less GSH means less protection against damage from oxidative stress
• Oxidative stress from infection, drugs, broad beans causes:
- lipid peroxidation
(cell membrane damage, lack of deformability leads to mechanical stress)
- protein damage - causes aggregates of cross-linked haemoglobin called Heinz bodies
• These are recognised as defective by RES and are removed by haemolysis
Why does pyruvate kinase deficiency cause defects in RBC metabolism?
- pyruvate kinase: final enzyme in glycolysis
- Rare genetic defects in this enzyme occur in some patients
- RBCs lack mitochondria so depend on glycolysis for energy production
- defective glycolytic pathway causes RBCs to rapidly become deficient in ATP and they undergo haemolysis
What are causes of acute blood loss?
- injury
- surgery
- childbirth
- ruptured blood vessel
What are NSAIDs used for and how can they induce GI injury/ bleeding?
- nonsteroidal anti-inflammatory drugs are used for treatment of conditions with pain and inflammation e.g. aspirin, ibuprofen, naproxen
- induce GI injury/ bleeding via inhibition of cyclooxygenase activity and via direct cytotoxic effects on epithelium
What is chronic bleeding?
A small amount of bleeding continuing over a long time may result in a significant blood loss
What are the most common causes of chronic bleeding?
• Heavy menstrual bleeding • Repeated nosebleeds • Haemorrhoids • Occult gastrointestinal bleeding (blood lost in stool) - Ulcers (stomach or small intestine) - Diverticulosis - Polyps in large intestine - Intestinal cancer • Kidney or bladder tumours (blood lost in urine)
In which two general sites can damage to RBCs occur?
- within blood vessels (intravascular haemolysis)
- within the RES system (extravascular haemolysis)
What happens in autoimmune haemolytic anaemias?
Autoantibodies bind to the RBC membrane proteins causing them to be recognised by macrophages in the spleen and become destroyed
Symptom of splenomegaly as the spleen is doing extra work
What is haemolytic anaemia?
In haemolytic anaemias red cells are destroyed more quickly as they are abnormal or damaged
Why can haemolytic anaemias result in splenomegaly?
as the spleen is doing
extra work to remove the extra damaged blood cells
What is the Role of the reticuloendothelial system?
Macrophages in spleen and other tissues of RES remove damaged or defective red cells e.g. in membrane,
enzyme & haemoglobin disorders.
How can myelofibrosis result in the development of anaemia?
- proliferation of mutated haemopoetic stem cells results in reactive bone marrow fibrosis
- Fibrotic marrow with little space for haemopoiesis
- mutated progenitor cells from marrow can also colonise liver and spleen —> extramedullary haemopoiesis. Results in enlarged liver and spleen
How can Thalassemia result in the development of anaemia?
- inherited disorders resulting from decreased/ absent alpha or beta globin chain production
- imbalance in composition of haemoglobin a2 or beta2 tetramer results in defective microcytic hypochromic RCs (small, pale)
- severity depends on type e.g. lack of 3 of 4 alpha globin genes leads to Hb H disease —> severe splenomegaly, microcytosis, haemolysis
What are two key features that can help to work out the cause of an anaemia?
- the RBC size - macrocytic (> 100 fl), microcytic (< 80 fl) normocytic (8-100 fl)
- the presence/ absence of reticulocytosis —> should be increased if BM has responded normally to anaemia
