Pathophysiology of Anaemia Flashcards
1
Q
What are the requirements for normal RBC production?
A
- Drive (EPO)
- Recipe (genes)
- Ingredients (iron, B12, folate and minerals)
- Functional bone marrow
2
Q
What is transferrin (Tf)?
A
- Glycoprotein synthesised in hepatocytes that has 2 iron binding domains and delivers iron to all tissues
3
Q
What is Hepcidin?
A
- The ‘low iron’ hormone and reduces levels of iron in the plasma by binding to ferroportin and degrading it
- This reduces iron absorption and decreases iron release from the RES
- It is synthesised in the liver and requires HFE for its production
4
Q
What are the signs and symptoms of anaemia?
A
- General
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised RR
- Specific7
- IDA
- Kolionychia (spoon shaped nails)
- Atrophic glossitis (smooth tongue)
- Angular chelitis/stomatitis (red patches at corners of mouth)
- Brittle hair and nails
- Oesophageal web (Plummer Vinson Syndrome)
- Haemolytic anaemia
- Jaundice
- Splenomegaly
- Red urine in the morning (PNH)
- Pernicious anaemia (B12 deficiency)
- Peripheral neuropathy with numbness and parasthesia
- Loss of vibration sense or proprioception
- Visual changes
- Mood or cognitive changes
- IDA
5
Q
What are the causes of IDA?
A
- Insufficient dietary iron
- Increased requirement (i.e. pregnancy)
- Iron being lost (most common cause in adults, i.e. menstruation, slow bleeding from CRC)
- Inadequate iron absorption (mainly absorbed in the duodenum and jejunum, requries acid from the stomach to keep it in the soluble form - Fe2+, medications such as PPIs interfere, conditions like coeliac and Crohn’s also affect absoprtion)
6
Q
How is IDA diagnosed and treated?
A
- Transferring saturation = Serum iron/TIBC
- In IDA:
- Low serum ferritin (ferritin is the form that iron takes when it is deposited and stored in cells, released in inflammation)
- Hypochromic microcytic RBCs on blood film
- Treat is replacement with ferrous sulphate, ferrous gluconate and IV iron, Hb should rise by around 10g/l/week - remember to discover cause
7
Q
What is the pathophysiology of ACD?
A
- RES iron blockage/iron trapped in macrophages, reduced EPO response and depressed marrow activity/cytokine marrow depression
8
Q
How is ACD diagnosed?
A
- N/↓ MCV/MCH
- ↓ Iron
- ↓ TIBC
- ↑ ESR
- ↑/N Ferritin
- Hypochromic mycrocytic or normochromic normocytic RBCs on blood film
9
Q
Why does B12/folate deficiency cause anaemia?
A
- Disparity in rate of synthesis or precursors of DNA
- Ineffective erythropoiesis (death of mature cells whilst still in marrow)
10
Q
How is B12/folate deficiency diagnosed and treated?
A
- Diagnosis:
- Intrinsic factor antibody
- Gastric parietal cell antibody
- Megaloblastic anaemia on blood film
- Raised bilirubin
- Raised LDH
- Management:
- Dietary deficiency with oral replacement with cyanocobalamin unless deficiency is severe.
- In pernicious anaemia IM hydroxycobalamin is required.
- If folate deficiency must treat B12 deficiency first and then treat with folic acid.
11
Q
What is the pathophysiology of B12 deficiency?
A
- Parietal cells produce a protein called intrinsic factor which is essential for the absorption of vitamin B12 in the terminal ileum.
- Pernicious anaemia is an autoimmune condition where antibodies form against parietal cells or intrinsic factor leading to reduced B12 absorption.
12
Q
What is the most common cause of folate deficiency?
A
- Lack of dietary intake
13
Q
What are haemoglobinopathies?
A
- Normal Hb consists of 2 alpha and 2 beta globin chains
- Inherited conditions causing a relative lack of normal globin chains due to absent genes (thalassaemias) or variants (abnormal) globin chains (i.e. sickle cell disease)
14
Q
What are problems with alpha globin chains?
A
- Autosomal recessive condition
- Most people have 4 alpha globin chains - α+ thal trait (missing one)
- Homozygous α+ thal trait (missing two, one on each allele)
- α0 thal trait (missing two α, both on same allele)
- HbH disease (missing three) - α thal major (missing four, incompatible with life in utero)
- Management:
- Monitoring of FBC
- Monitoring for complications
- Blood transfusions
- Splenectomy
- Bone marrow transplant
15
Q
- What are problems with beta globin chains?
A
- Beta thalassaemia (missing B genes – should have 2) trait isn’t pathogenic but leads to small red cells.
- Beta thalassaemia minor patients are carriers (one abnormal, one normal)
- Beta thalassaemia intermedia (patients have two defective genes, one defective and one deletion) - requires occasional blood transfusions
- Beta thalassaemia major is an AR disorder where the body is unable to make adult haemoglobin (HbA) leading to significant dyserythropoeises - requires regular transfusions, iron chelation and splenectomy. Bone marrow transplant can be curative.
- Main problem with this is it leads to iron deficiency.
16
Q
- What is sickle cell disease?
A
- AR genetic condition that leads to sickle (crescent) shaped RBCs.
- Due to a point mutation on the beta gene in chromosome 11.
- Makes blood cells rigid so they can’t bend through blood vessels
- Clinical result is haemolysis and vaso-occlusion (hypoxia)
17
Q
What types of acquired haemolytic anaemias are there?
A
- Autoimmune (warm type - IgG, cold type - IgM)
- Alloimmune (transfusion reactions and haemolytic disease of the new-born)
- Paroxysmal nocturnal haemoglobinuria (genetic mutation in haematopoietic stem calls results in loss of proteins on surface or RBC that inhibits the complement cascade)
- Microangiopathic haemolytic anaemia (small blood vessels have structural abnormalities that cause haemolysis)
- Prosthetic valve related haemolysis
18
Q
How does the Direct Coombs Test work?
A
- Detect antibody on RBC surface
- RBCs coated with IgG autoantibodies
- Add antihuman Ig which forms lattice for RBCs agglutinate
- Positive in patients with haemolytic anaemia
19
Q
How does the Indirect Coombs Test work?
A
- Detect RBC antibodies in plasma
- Take RBC samples from unit intended for transfusion and a sample of patient plasma
- Mix both together
- If plasma contains autoantibodies they will stick to the RBC
20
Q
Causes of microcytic anaemia (remember TAILS)
A
- Thalassaemia
- ACD
- IDA
- Lead poisoning
- Sideroblastic anaemia
21
Q
Causes of normocytic anaemia (remember 3As and 2 Hs)
A
- Acute blood loss
- ACD
- Aplastic anaemia
- Haemolytic anaemia
- Hypothyroidism
22
Q
Causes of macrocytic anaemia (megaloblastic or normoblastic)
A
- Megaloblastic (impaired DNA synthesis - rather than dividing it keeps growing into a larger, abnormal cell caused by vitamin deficiency)
- B12 deficiency
- Folate deficiency
- Normoblastic anaemia
- Alcohol
- Reticulocytosis
- Hypothyroidism
- Liver disease
- Drugs (i.e. azathioprine)
23
Q
How is anaemia investigated?
A
- Initial Investigations:
- Haemoglobin
- Mean Cell Volume (MCV)
- B12
- Folate
- Ferritin
- Blood film
- Further Investigations:
- Oesophago-gastroduodenoscopy (OGD) and colonoscopy to investigate for GI cause
- Bone marrow biopsy if cause unclear
24
Q
What types of inherited haemolytic anaemias are there?
A
- Hereditary Spherocytosis
- Hereditary Elliptocytosis
- Thalassaemia
- Sickle Cell Anaemia
- G6PD Deficiency
25
Pathophysiology and management of hereditary spherocytosis
* Most common inherited haemolytic anaemia
* AD condition
* Causes sphere shaped RBCs that are fragile and break down easily when passing through the spleen.
* Treat with folate supplementation and splenectomy.
NB - Hereditary eliptocytosis is the same except with ellipse shaped RBCs
26
Pathophysiology and management of G6PD deficiency
* Defect in RBC enzyme G6PD.
* X-linked recessive.
* Causes crises triggered by infections, medications and fava beans.
* Heinz bodies on blood film.
* Diagnosis by G6PD enzyme assay.
* Medications include primaquine (antimalarial), ciprofloxacin, sulphonylureas, sulfasalazine and other sulphonamide drugs.
27
Autoimmune haemolytic anaemia
* Antibodies attack RBCs
* Warm type - more common and haemolysis occurs at normal temperatures. Usually idiopathic.
* Cold type - Lower temperatures antibodies attach to RBCs causing them to clump together (agglutinate) and break down. It is often secondary to conditions like lymphoma, leukaemia, SLE and infections like mycoplasma, EBV, CMV and HIV.
* Managed with blood transfusions, prednisolone, rituximab and splenectomy.
28
Alloimmune haemolytic anaemia
* Occurs when either foreign RBCs circulating in the patients blood cause a reaction that destroys those cells or ther is a foreign antibody circulating in their blood that acts against their own RBCs.
29
Complications of sickle cell anaemia
* Anaemia
* Increased risk of infection
* Stroke
* Avascular necrosis in large joints such as the hip
* Pulmonary hypertension
* Painful and persistent penile erection (priapism)
* Chronic kidney disease
* Sickle cell crises
* Acute chest syndrome
30
Management of sickle cell anaemia
* Avoid dehydration
* Ensure vaccines up to date
* Antibiotic prophylaxis against infection (penicillin V)
* Hydroxycarbamide can be used to stimulate production of HbF
* Blood transfusion for severe anaemia
* Bone marrow transplant can be curative
* Management of sickle cell crises is supportive
31
Management of vaso-occlusive crisis in SCD
* Sickle shaped blood cells clogging capillaries causing distal ischaemia
* Associated with dehydration and raised haematocrit
* Can cause priaprism in men - urological emergency.
32
Management of splenic sequestration crisis in SCD
* RBCs blocking blood flow within the spleen
* Causes enlarged and painful spleen
* Pooling of blood can lead to hypovolaemic shock
* Management with blood transfusions and fluid resuscitation
33
Management of aplastic crisis
* Situation where there is temporary loss of creation of new blood cells
* Most commonly triggered by parovirus B19
* Management with supportive blood transfusions
34
Management of acute chest syndrome in SCD
* Diagnosis requires:
* Fever or respiratory symptoms
* New infiltrates seen on CXR
* Medical emergency managed with:
* Antibiotics or antivirals for infections
* Blood transfusions
* Incentive spirometry
* Artificial ventilation with NIV
