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Medicine Y1M2- Blood, Cardiovascular and Respiratory Systems > Anaemia- diagnosis and classification > Flashcards

Anaemia- diagnosis and classification Flashcards

1
Q

What are the physiological adaptations to anaemia?

A
  • Produce more RBCs
  • Increased cardiac output
  • Increased volumes of inspired o2
  • Patients with less respiratory reserve e.g those with lung/heart conditions, the very young/elderly, are more susceptible to anaemia
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2
Q

What are the symptoms of anaemia?

A
  • Light headed/ Dizzy
  • Fatigue
  • Weakness
  • Short of Breath
  • Palpitations
  • Chest Pain
  • Confusion
  • Reduced Consciousness
  • Increased Respiratory
  • Rate
  • Increased Heart Rate
  • Pallor
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3
Q

What 3 factors lead to anaemia?

A
  • Failure in production (e.g haem, RBCs)- RBC production relies on haem synthesis, globin chain and incorporate to form Hb, effective erythropoeisis and functional bone marrow environment
  • Loss of RBCs (blood loss)
  • Destruction of RBCs (e.g splenomegaly)
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4
Q

Haem synthesis and iron metabolism

A

-Haem synthesis involves a complex metabolic pathway resulting in the incorporation of an Fe2+ atom results in the formation of haem
- Relies on iron intake and GI Tract absorption: if disrupted(coeliac)/ insufficient can lead to anaemia
Increased use due to increased erythropoiesis to match demand – eg bleeding, haemolysis- polycythaemia vera (where bone marrow produces too many RBCs)

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5
Q

How is iron absorbed and what is its significance?

A

Iron absorbed across the gastrointestinal epithelial cells
Haem Iron&raquo_space;> Non Haem Iron
Free Intracellular Iron is toxic to cells. The protein ferritin packages intracellular iron to protect the cell from these effects. Ferritin levels correspond to Iron Stores
Low Ferritin = Iron Deficiency
High Ferritin = Suggestive of normal / increased iron stores*
*As ferritin is an acute phase protein (like CRP) many other things can cause the ferritin to rise (eg infection, inflammation, liver disease etc). Therefore a normal / high ferritin does not rule out Iron Deficiency

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6
Q

How is iron profiling assessed?

A

Serum Iron – Significant variation during the day and acute illness
Ferritin – Increased with increasing Iron, inflammation (acute phase reactant), Liver Disease
Down in deficiency
Transferrin – Increased production in iron deficiency, measured by determining the Total Iron Binding Capacity (TIBC)
Transferrin Saturation – Measures the serum iron/TIBC, Reduced in Iron Deficiency

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7
Q

Iron deficiency anaemia

A

Fail to produce sufficient haemoglobin which provides the red pigment to erythrocytes.
Therefore cells are;

• Hypochromic (pale)

  • Low MCH
  • Low MCHC

• Microcytic (small)
-Low MCV

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8
Q

Globin synthesis

A

3 types of haemoglobin- HbA (2a 2B)-98%
HbF (2a 2G)- ~1%
HbA2 (2A 2D) <3.5%

In globin synthesis, mutations can;
• Inhibit synthesis of the globin completely
• Inhibit synthesis partially
• Affect normal structure/function of Hb

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9
Q

Haemoglobinopathies- classification

A

Quantitative = Reduced production of functioning Globin Chains
-Alpha Thalassaemia- • ⍺0 type mutations completely inhibit synthesis of the ⍺ globin
• ⍺+ type mutations partially inhibit synthesis of the ⍺ globin
⍺0 trait = microcytic hypochromic anaemia (usually mild)
Hb Barts = No Alpha chains –incompatible with post uterine life
⍺+ trait = carrier state - unaffected Hb H – Usually have
a Thalassemia Intermedia phenotype. Variable spectrum of disease

-Beta Thalassaemia- see flashcard

Qualitative = Change in Haemoglobin Structure/Function
-Sickle Cell Disease

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10
Q

Beta thalassaemia

A

Thalassemia- abnormal haemoglobin production
• β0 type mutations completely inhibit synthesis of the β globin
• β+ type mutations partially inhibit synthesis of the β globin
-Imbalance between the production of the alpha chains and Beta chains which should form the normal haemoglobin
Severity depends upon;
1. The type of mutation
2. Whether it is heterozygous
3. Whether there is a co-inheritance of another globin gene mutation e.g. Sickle cell disease

Pathophysiology
The failure of β globin chain production results in an imbalance between ⍺ and β changes
Free ⍺ chains are highly unstable, forming intracellular inclusions which interfere with the cell membrane;
• Intramedullary destruction of red cell precursors
(ineffective erythropoiesis)
• Shortened life span of red cells that do make
it into the circulation (haemolysis)

3 types- Major, intermedia and minor
Major is transfusion dependent, high output heart failure (β0/ β0 or β+/ β0)
Intermedia ( β+/ β0 or β+/ β+) may eventually be transfusion dependent
Minor ( β0/ β or β+/ β) is rarely TD- microcytic cells, often confused with IDA

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11
Q

Sickle cell disease- cause and difference between SCD and SC trait

A
  • On chromosome 11 (B globin gene), CAG, CTC codes for a normal (5 Glu 7) molecule- normal B chain
  • In SCD, point mutations occurs- GtG, CaC- codes for (5 Val 7)- abnormal B globin chain (HbS)
  • Heterozygotes (SC Trait) have 2a 1b 1(bs) haemoglobin (HbAS)
  • Homozoygous (SCD) have 2a 2(bs) (HbSS)
    SC trait
    • A benign carrier state
    • Generally not affected by any of the complications seen in
    homozygous individuals
    • Important to know about largely with regard to reproductive planning
    etc
    • Appears to be protective against P. falciparum- MALARIA
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12
Q

Complications related to SCD/trait

A

Infection, hypoxia (altitude, surgery, obstetric delivery, vigorous exercise) acidosis, dehydration can lead to low o2 which can lead to HbS polymerising long rope like fibres of Hb.

  • Vaso-occlusion may occur in individuals with SCD/T: RBCs are irreversibly sickled after these fibres interact with RBCs. They are more adherent to endothelium in microvasculature
  • RBCs also have a shortened lifespan (haemolytic anaemia), may release free haem.
  • Small vessel obstruction may occur in spleen, lungs, kidney, bone, liver, brain etc

Acute Complications- painful crisis, acute chest syndrome, priapism, stroke, acute anaemia, aplastic crisis, multi-organ failure, acute Cholecystitis

Chronic complications- nephropathy, chronic pain, pulmonary hypertension, retinopathy, neurological impairment, hyposplenism leading to Infection and Immunodeficiency

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13
Q

Erythropoeisis

A

-The process of red blood cell production coming from erythropoeitic stem cells in the bone marrow
- Erythropoeisis is controlled carefully by EPO-
Increased O2 demand ( inc. metabolic demands, infection, exertion) and decreased O2 supply ( reduced po2- altitude, resp/circ failure)= optimisation of Hb O2 binding
-Increased Cardiac Output (Stroke Volume x Heart Rate)
-Increased Respiratory Rate
-Increased circulating Haemoglobin from increased RBC

EPO- HIF = Hypoxia inducible factor> Under Hypoxic conditions – HIF1⍺ is stabilised and binds to a hypoxia response element (HRE) at the 3’ element of the EPO gene>Increased EPO gene transcription and translation> EPO production from interstitial cells of the
kidney

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14
Q

What are reticulocytes?

A
  • Immature red blood cells with no nucleus- the last stage of red cell development before terminal differentiation to a mature red cell and release into the peripheral circulation.
  • Numbers are high in the bone marrow and low in the peripheral blood
  • Measuring the peripheral blood reticulocyte count is a useful marker of erythropoietic activity
  • Low Retics = low levels of erythropoiesis
  • High Retics = high levels of erythropoiesis
  • The presence gives the blood film an appearance of polychromasia due to retained ribosomal RNA
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15
Q

What role do folate and Vitamin B12 play in DNA synthesis?

A
  • Key roles in the formation of purines and pyrimidines –the bases of DNA
  • Humans cannot synthesis either B12 or Folate. Therefore we are dependent on effective dietary intake.
  • Intrinsic Factor is produced by gastric parietal cells – this is critical to B12 absorption (occurs in the distal small intestine)
  • B12 found in animal sources e.g meat, dairy- vegans at risk
  • Coeliacs, Crohns and pernicious anaemia can lead to reduced absorption of b12
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16
Q

Anaemia of chronic disease- what is it and how is it caused?

A

Form of anaemia seen in chronic infection, chronic immune activation, and malignancy.

  • Produce elevation of interleukin-6, which stimulates hepcidin production + release from the liver> shuts down ferroportin (a protein that controls export of iron from the gut and from iron storing cells)> circulating iron levels are reduced: Failure in RBC production
  • Other mechanisms may also play a role, such as reduced erythropoiesis ( due to relative decrease in EPO)
17
Q

Red cell aplasia

A

Describes the failure of erythropoiesis occurring in isolation from the rest of haematopoiesis. It is marked by severe reticulocytopenia.
Causes include;
• Congenital- Diamond Blackfan Anaemia – genetic mutation affecting ribosome function.
Differentiation block during the early stages of RBC development. Multiple different genes implicated and a spectrum of disease.
Some variants of RCA
• Acquired- Infection: Parvovirus B19 can cause transient block in erythropoiesis. Can be significant generally in patients with another problem in RBC/ Hb production or destruction such as SCD, haemolytic anaemias etc as patients have v. little reserve and have a high demand for production of red cells just to “stand still”. Other infections implicated include HIV, CMV, EBV, Hepatitis A,B,C.

  • Drugs – eg previous cases of antibodies to recombinant EPO injections have been implicated
  • Autoimmunity – eg SLE, RA etc
  • Malignancy – lymphomproliferative malignancy, other solid tumours
18
Q

Failure of production- 4 types and their effects

A
  1. Haem- Iron Deficiency

2.Globin Chains (Haemoglobinopathies)-
Quantitative – Thalassaemia (a/b)
Qualitative –Sickle Cell Disease

3.Erythropoiesis- B12/Folate Deficiency
-Genetic Disorder
-Destruction of Red Cell Precursors – Red Cell Aplasia
Insufficient EPO – Chronic Kidney Disease
-Drugs eg Chemotherapy

  1. Non-Functioning Bone Marrow Environment
    - Immune Destruction – eg aplastic anaemia
    - Malignancy – eg leukaemia, myeloma, solid tumour mets
    - Infiltrative disease – eg Gauchers
19
Q

Clinical- how to approach loss of red cells

A

Always think of possible bleeding – either concealed or overt
GI bleeding
• Haematemesis
• Malaena (black stools, upper gi bleeding) / PR (perirectal) bleeding
• Raised Urea

Gynae bleeding
• Heavy Menstruation
• Post Menopausal bleeding
ALWAYS INVESTIGATE FOR AND TREAT THE
UNDERLYING CAUSE
20
Q

Destruction of red cells

A

Haemolytic anaemias- any process in which there is inc. breakdown or destruction of mature RBCs resulting in a shortened life span and need for increased erythropoiesis to compensate.
They become clinically apparent whenever;
Breakdown > Production = Anaemia
Haemolysis can be intra or extravascular (e.g liver/kidney)

21
Q

Haemolytic anaemia- diagnosis and symptoms

A

Diagnosis
• Anaemia (can be mild > severe)
• Raised Bilirubin- iron released from haemolysis for recycling> unconjugated bilirubin> ( with UDP-glucuronosyltransferase) Conjugated bilirubin> excretion in bile

• Raised LDH- cytoplasmic enzyme- good marker of cell turnover, released when RBCs broken down. It is therefore high in Haemolysis
Other causes of high LDH include;
• Malignancy – particularly high grade lymphomas etc
• Other tissue damage eg MI, Liver failure etc.

  • Decreased Haptoglobin- involved in bilirubin production so very low in IV haemolysis
  • Increased Reticulocytes
  • Spherocytes, Schistocytes (fragments)
  • Positive Coombes Test
22
Q

Haemolytic anaemia- Congenital vs Acquired

A 
Congenital
• Membrane Problem
-Hereditary Spherocytosis
-Hereditary Elliptocytosis
• Enzyme Problem
- G6PD deficiency
- Pyruvate Kinase deficiency
• Haemoglobin Problem
- HbSS (Sickle Cell disease)
- Thalassemia
-Unstable Haemoglobin variant
Acquired
 • Mechanical
– March Haemolysis
– Mechanical valve
• Immune
– Autoimmune: warm, cold
– Alloimmune: Eg Haemolytic disease of Newborn
• Drugs
– Cephalosporins, NSAIDS, Penicillin, Nitrofurantoin, Dapsone etc
• Infection
– Malaria
• Other
– Microangiopathic Haemolytic anaemia
– Paroxysmal Nocturnal Haemoglobinuria
23
Q

A systematic approach to anaemia

A

• Are the white cell and platelets counts normal or abnormal?
• Think bone marrow disorders if more than one haematopoietic lineage is affected
Look for the red cell indices
• Is this micro, normo or macrocytic
• Is this hypochromic or is there evidence of polychromasia
The Red Cell Indices can guide you..
• Microcytic (Low MCV)
-Iron Deficiency, thalassemia

• Macrocytic (High MCV)
- B12 and/or Folate deficiency, Alcohol, Drugs (HU, EPO, Chemotherapy) , Haemolysis, Hypothyroidism Bone Marrow Infiltration, Pregnancy

• Normocytic (Normal MCV)- Acute Bleeding, Anaemia, Chronic Disease, Mixed Aetiology

Blood film- look at the:

  • Red Cell Size and Shape
  • Red Cell Pigmentation
  • Red Cell Inclusions
  • White Cell and Platelet Morphology

Medicine Y1M2- Blood, Cardiovascular and Respiratory Systems (55 decks)

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