Session 7 ILO's Flashcards
Define the term anaemia
Haemoglobin concentration lower than the normal range
(normal range varies with gender, age and ethnicity so the point at which a patient becomes anaemic depends on those parameters)
It is NOT a diagnosis
It is a clinical manifestation of an underlying disease state
It is important to ESTABLISH CAUSE
What are the 3 categories of reasons for the development of anaemia?
- Bone Marrow Reasons
- RBC reasons
- Removal/Loss reasons
Reasons anaemia can develop (bone marrow)
- Reduced or dysfunctional erythropoesis
- Abnormal Haem synthesis
- Abnormal globin chain synthesis
Reasons anaemia can develop (RBC)
Abnormal structure
Mechanical damage
Abnormal metabolism
Reasons anaemia can develop (removal/loss)
Excessive bleeding
Increased removal by reticuloendothelial system
Reasons for reduced/dysfunctional erythropoesis (5)
Lack of erythropoietin (chronic kidney disease as kidney produces it)
Bone marrow cannot respond to erythropoietin (eg after chemo)
If marrow is infiltrated by cancer cells or fibrous tissue (myelofibrosis), the number of normal haemopoeitic cells is reduced
Anaemia of chronic disease = no iron available to marrow for bc production
Myelodysplastic syndromes (rare forms of blood cancer) = abnormal clones of stem cells so no capacity to make RBC or WBC
Reasons haemoglobin synthesis can be affected
- Sideroblastic anaemia
- Iron deficiency anaemia
- Anaemia of chronic disease - results in a lack of functional iron
- Mutations in genes encoding gloin chain proteins ( we see that in patients with a and b thalassaemia and sickle cell disease)
What is defect in haem pathway called?
Sideroblastic anaemia
Inherited reasons for haemolytic anaemia
- Mutations in genes coding for proteins in membrane and cytoskeleton of RBC
- Cause cells to be less deformable and more fragile
- They break up in circulation and removed by RES
= haemolytic anaemia (eg Hereditary spherocytosis)
Acquired reasons for haemolytic anaemia
Microangiopathic haemolytic anaemia (MAHA) from mechanical damage
Heat damage from severe burns
Osmotic damage (drowning in fresh water)
Reasons for mechanical damage in patients with MAHA (Microangiopathic haemolytic anaemia) occurs
Shear stress as cells pass through defective heart valve
Cells snag on fibrin strands in small vessels where clots have been formed and they break down (eg in Disseminated Intravascular Coagulation)
What would a blood film of blood cells with mechanical damage look like?
Schistocytes - fragments of RBC resulting from mechanical damage
Causes of defect in RBC metabolism
G6PDH deficiency
Pyruvate kinase deficiency
Why does G6PDH deficiency cause anaemia?
- Mature RBC’s don’t have mitochondria to give energy, they rely on certain glycolytic pathways
- Decreased G6PDH = Lack of NADPH
- Lack of NADPH = lower GSH (glutathione)
- lower GSH = less protection of RBC from oxidative stress
- Oxidative stress
- Oxidative stress (eg from infection, drugs like anti malaria, and broad beans)
- Oxidative stress leads to
Lipid peroxidation (leads to cell membrane damage) and protein damage to RBC
=
Heinz bodies (aggregates of cross linked haemoglobin)
Red cells recognised by RES as defective and removed
Why does pyruvate kinase deficiency cause anaemia?
- RBC have no mitochondria so depend on glycolysis for energy production
- Pyruvate kinase is final enzyme of glycolysis
- Some patients may have rare genetic defects in this enzyme
- A defective glycolytic pathway causes RBC’s become deficient in ATP and undergo haemolysis
What are the 3 excessive bleeding causes of anaemia?
- Acute blood loss
- Chronic NSAID’s (Nonsteroidal anti-inflammatory drugs)
- Chronic bleeding (most common)
Acute blood loss causes of anaemia
Injury
Childbirth
Surgery
Ruptured vessel
Chronic excessive bleeding causes of anaemia
- Heavy menstrual bleeding
- Repeated nosebleeds
- Haemorrhoids
- GI bleeding (blood loss in stool)
- Kidney/bladder tumours (blood loss in urine)
Causes of GI bleeding
Ulcers (stomach or intestine) Polyps in large intestine Intestinal cancer NSAIDS Diverticulotis
How can NSAID usage lead to anaemia?
Nonsteroidal anti-inflammatory drugs treat conditions with pain and inflammation:
- Asprin
- Ibruprofen
- Naproxen
They Induce GI bleeding by:
- Inhibit cyclooxygenase activity
- Direct cytotoxic effects to epithelium
Describe the role of the Reticuloendothelial system in causing anaemia and
Describe what happens in autoimmune haemolytic anaemias
What can occur as a result of haemolytic anaemias?
Haemolytic anaemia = RBC destroyed more quickly due to abnormality or damage
Autoimmune haemolytic anaemia:
- Autoantibodies bind to RBC membrane proteins causing them to be recognised by macrophages in spleen and destroyed
(splenomegaly often occurs with haemolytic anaemias as the spleen is doing extra work)
How can myelofibrosis lead to anaemia?
How can thalassemia lead to anaemia?
Understand the important causes of microcytic anaemia
T A I L S
- Thalassaemia
- Anaemia of chronic disease (sometimes)
- Iron Deficiency
- Lead Poisoning
- Sideroblastic Anaemia
Understand the important causes of macrocytic anaemia
- Vitamin B12 deficiency
- Folate deficiency
- Myelodysplasia
- Liver disease
- Alcohol Toxicity
Understand the important causes of normacytic anaemia
Normocytic:
Could be because they have got a combo of microcytic and microcytic cells
Primary bone marrow failure (e.g. aplastic anaemia)
Secondary bone marrow failure (HIV)
What are the signs of anaemia?
Pallor Tachycardia Systolic flow murmur Tachypnoea (fast breathing) Hypotension
List the specific signs associated with the cause of anaemia
Koilonychia (spoon nails, iron deficiency)
Angular Stomatitis (inflammation around mouth, iron deficiency)
Glossitis (inflammation and smooth tongue, Vit B12 deficiency)
Abnormal facial bone development (Thalassaemia)
What are the symptoms of anaemia?
Shortness of breath Headaches Angina Weakness/lethargy Confusion Palpitations Claudication
What are the common clinical features of haematinic deficiency (iron, vitamin B12 or folate deficiency)? (does that mean symptoms?)
n/a
What are the important underlying causes of haematinic deficiency (iron, vitamin B12 or folate deficiency)? FOLATE
Dietary deficiency (Poor diet)
Increased requirements - pregnancy, increased erythropoiesis (e.g haemolytic anaemia) , severe skin disease (psoriasis)
Disease of duodenum or jejunum (coeliac, crohns)
Drugs that inhibit dihydrofolate reductase (Methotrexate)
Alcoholism (poor diet and damage to intestinal cells)
Urinary loss of folate in Liver disease/Heart failure
What are the important underlying causes of haematinic deficiency (iron, vitamin B12 or folate deficiency)? VITAMIN B12
Dietary deficiency (vegan diet lacking B12 supplementation)
Lack of intrinsic factor - Pernicious anaemia
Disease of ileum (Crohns)
Lack of transcoalbumin (congenital)
Chemical inactivation of B12 (nitrious oxide gas use/smartwhip)
Parasitic infestation (rare tapeworm found in fish traps B12)
Some drugs chelate Intrinsic factor (hypercholestrolaemia drug Cholestyramine)
Describe the role of haematinic replacement treatment
na
Describe the complications associated with haematinic replacement treatment
na
List the different causes of microcytic anaemia
T A I L S
- Thalassaemia
- Anaemia of chronic disease (sometimes)
- Iron Deficiency
- Lead Poisoning
- Sideroblastic Anaemia
Give examples of good dietary sources of haem iron
na
Give examples of good dietary sources of non-haem iron
na
Give an overview of iron absorption
na
Give an overview of iron transport
na
Give an overview of iron uptake
na
Give an overview of iron storage
na
Give an overview of iron metabolism
na
Describe how iron deficiency leads to anaemia
na
Describe how iron deficiency anaemia is diagnosed
na
Describe how iron overload can occur
na
Describe the aetiology (causes) of Hereditary Haemochromatosis
na
Describe the treatment of Hereditary Haemochromatosis
na
