Red Cells 2 Flashcards

1
Q

what are some factors influencing the normal range of haemaglobin?

A

Age

Sex

Ethnic origin

Time of day sample taken

Time to analysis

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2
Q

what are the Reference ranges of haemaglobin? (vary with age and sex)

A
  • Male 12-70 (140-180)
  • Male >70 (116-156)
  • Female 12-70 (120-160)
  • Female >70 (108-143)

As you get older there is a physiological drop in hemoglobin

Male different due to effect of testosterone

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3
Q

what are the clinical features of anaemia?

A

General features due to reduced oxygen delivery to tissues:

  • Tiredness/pallor
  • Breathlessness
  • Swelling of ankles (degree of heart failure)
  • Dizziness
  • Chest pain
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4
Q

what do the lcinical features of anaemia depend upon?

A

Depend on age, speed of onset and Hb level

Will depend on a fall from the baseline that the patient is used to

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5
Q

what are some anaemia clinical features that are related ot the underlying cause?

A

Evidence of bleeding: Menorrhagia, Dyspepsia, PR bleeding

Symptoms of malabsorption - Diarrhoea, Weight loss

Jaundice

Splenomegaly/Lymphadenopathy

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6
Q

Anaemia Pathophysiology:

What is A

A

Cellularity

Stroma

Nutrients

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7
Q

Anaemia Pathophysiology:

What is B

A

Membrane

Haemaglobin

Enzymes

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8
Q

Anaemia Pathophysiology:

What is C

A

Blood loss

Haemolysis

Hypersplenism

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9
Q

Red cell indices - Automated measurement of red cell size and haemoglobin content

what are 2 important measurements?

A

MCH = Mean cell haemoglobin

MCV = Mean cell volume (cell size)

Can give a morphological description of anaemia – and a clue as to cause!!

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10
Q

what are the different morphological descriptions in anaemia?

A

Hypochromic – less colour

Microcytic – small

Small pale cells

Normochromic normocytic – normal amount of haemaglobin and on average they are a normal size. Many anaemias have this form. May have sickle cell and machine cant say what shape

Macrocytic – big red cells, usually less haemaglobin in them

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11
Q

what is shown here?

A

5 different patients

Don’t need to remember reference ranges

  1. Got bigger cells so got less cells and on average have more in it
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12
Q

What investigation is A?

A

serrum ferritin

Most common cause is Iron deficiency – do a serum ferritin

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13
Q

What investigation is B?

A

Reticulocyte count

Lots of causes so blood film important there to see what it looks like, reticulocyte count can be important, last stage of red cell development and if bleeding your reticulocyte count will go up to compensate and same in haemolysis. Reticulocyte count can be low in aplastic anaemia and tells if bone marrow is working or not

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14
Q

What investigation is C?

A

B12/FOlate

Bone Marrow

Commonest cause if B12/folate deficiency and if these are normal then may. Be a problem in the bone marrow

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15
Q

what is shown here?

A

Hypochromic, microcytic anaemia

Area of central pallor is about normal in the left photo

Right photo - RBC should be same size as a lymphocyte as seen in dark purple, more pale in the middle

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16
Q

in Hypochromic microcytic anaemia, if serum ferritin is low, then what is it likely to be?

A

iron deficiency

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17
Q

in Hypochromic microcytic anaemia, if serum ferritin is normal or increased, then what is it likely to be?

A

Thalassaemia

Secondary Anaemia

Sideroblastic anaemia (a disorder where the body produces enough iron but is unable to put it into the haemoglobin)

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18
Q

iron metabolism:

  • Dietary intake ________ by loss
  • Most of the body’s iron is in __ - And is “recycled”

Absorbed iron - bound to mucosal ______ and sloughed off Or transported across the basement membrane by ________

Then - bound to _________ in plasma

Stored as Ferritin - mainly in _____

A

balanced

Hb

ferritin

ferroportin

transferrin

liver

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19
Q

Ferratin is a measure of what?

A

iron stores

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20
Q

what is hepcidin?

A

Hepcidin synthesised in hepatocytes in response to ↑iron levels and inflammation – blocks ferroportin so reduces intestinal iron absorption and mobilisation from reticuloendothelial cells

(Transported from enterocytes and macrophages by ferroportin)

epcidin inhibits iron transport by binding to the iron export channel ferroportin

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21
Q

what is the Commonest cause of anaemia worldwide?

A

iron deficiency anaemia

Description not a diagnosis – establish cause!

22
Q

what would appear in the history and examination of a patient with iron deficiency anaemia?

A

History:

  • Dyspepsia, GI bleeding
  • Other bleeding, eg menorrhagia
  • Diet (NB children and elderly)
  • Increased requirement - pregnancy

Examination:

  • Signs of iron deficiency
  • Abdominal and rectal
23
Q

what are clinical features of iron deficiency?

A
24
Q

what are the causes of iron deifiency?

A

GI blood loss

Menorrhagia (menstrual periods with abnormally heavy or prolonged bleeding)

Malabsorption:

  • gastrectomy
  • coeliac disease
25
Q

what is the management of iron deficiency?

A

Correct the deficiency:

  • Oral iron usually sufficient
  • IV iron if intolerant of oral
  • Blood transfusion rarely indicated

Correct the cause:

  • Diet
  • Ulcer therapy
  • Gynae interventions
  • Surgery
26
Q

in Normochromic normocytic anaemia, if reticulocyte count is increased, what may the cause be?

A

Acute blood loss

Haemolysis

27
Q

in Normochromic normocytic anaemia, if reticulocyte count is normal or low, what may the cause be?

A

Secondary anaemia

Hypoplasia

Marrow infiltration

28
Q

what is secondary anaemia?

A

“Anaemia of chronic disease”

70% normochromic normocytic - 30% hypochromic microcytic

Defective iron utilisation - Increased hepcidin in inflammation, Ferritin often elevated

Identifiable underlying disease - infection, inflammation, malignancy

29
Q

what is haemolytic anaemia?

A

Accelerated red cell destruction (Decrease Hb)

Compensation by bone marrow (Increased Retics)

Level of Hb – balance between red cell production and destruction

30
Q

Haemolytic anaemia can be of what two forms?

A

Haemolysis can be extravascular or intravascular (or bit of both!)

Intravascular haemolysis is always pathological and not normal - Bursting in the blood vessels

31
Q

what are the causes of haemalytic anaemia?

A

Congenital: eg.

  • Hereditary spherocytosis (HS)
  • Enzyme deficiency (G6PD deficiency)
  • Haemoglobinopathy (HbSS)

Acquired:

  • Auto-immune haemolytic anaemia (Extravascular)
  • Mechanical eg.artificial valve (Intravascular)
  • Severe infection/DIC (Intravascular)
  • PET/HUS/TTP (Intravascular)
32
Q

aquired causes of haemolytic anaemia can either be immune or non-immune - which of this is mainly extravascular and which is mainly intravascular?

A

immune = mainly extravascular

non-immune = mainly intravascular

33
Q

what is the Direct Antiglobulin Test?

A

Detects antibody or complement on red cell membrane

Reagent contains either anti-human IgG or anti-complement

Reagent binds to Ab (or complement) on red cell surface and causes agglutination in vitro

Implies immune basis for haemolysis

If patient has antibodies against red blood cells (either own or transfused ones) then if they have antibodies on surface of red cells and the lab adds an antibody antibody and causes red cells to clump and it tells you that there is an antibody on the surface of red cells

34
Q

if the DAGT (direct antiglobulin test) is positive, what does this mean?

A

Positive = antibodies or complement there

(so if reticulocyte count is increased this can be due to haemolysis, haemolytic anaemia can be congenital and aquired. Aquired haemolytic anaemia can be immune related (extravascular) or it can be non-immune related (intravascular) and to determine if its immune related or not you do the DAGT)

35
Q

in haemolytic anaemia, what are the different kinds of immune haemolysis?

A

Warm Auto-antibody – bind to the patients cells at body temperature and causes haemolysis

Some antibodies only bind when the body is cold – these are rarer and often cause less of a problem

Alloantibody – antibodies against transfused cells

36
Q

explain what is happening here

A

Spleen removes the antibody and at same time nips part of the RC membrane and this results in the cells sphereing and you can see this on the blood film

Cold antibodies are often IgM

Warm antibodies cause haemolysis at room temperature

37
Q

what do red blood cells look line in Intravascular haemolysis? e.g. in a valve

A

Red cell fragments - “schistocytes”

(Schistocytes are fragmented red blood cells that can take on different shapes)

38
Q

haemolytic anaemia:

how do you work out if the patient is haemolysing?

A

FBC, reticulocyte count, blood film

Serum bilirubin (direct/indirect), LDH

Serum haptoglobin (will be low if someone is haemolysing)

39
Q

in haemolytic anaemia how do you work out the mechanism?

A

History and examination

Blood film

Direct Antiglobulin Test (Coombs’ test – tells you if immune or not)

Urine for haemosiderin/urobilinogen(free haemoglobin in circulation)

40
Q

what is the management of haemolytic anaemia?

A

Support marrow function - Folic acid

Correct cause:

  • Immunosuppression if autoimmune - Steroids, Treat trigger eg.CLL, Lymphoma
  • Remove site of red cell destruction - Splenectomy
  • Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular

Consider transfusion

41
Q

to test for macrocytic anaemia you do B12/folate assay or Blood film/Bone marrow

what can this reveal?

A
42
Q

B12/Folate Deficiency causes what?

A

Anaemia

Neurological symptoms (subacute combined degeneration of the cord in B12 deficiency)

43
Q

what are the causes of B12 deficiency?

A

Pernicious anaemia

Gastric/ileal disease

44
Q

what are the causes of folate deficiency?

A

Dietary

Increased requirements (haemolysis)

GI pathology (eg.coeliac disease)

45
Q

Body has B12 stores that ast for 6 months to a year so often a _______ process

A

chronic

46
Q

how is vitamin B12 absorbed?

A

Dietary B12 binds to intrinsic factor, secreted by gastric parietal cells

B12-IF complex attaches to specific IF receptors in distal ileum

Vitamin B12 bound by transcobalamin II in portal circulation for transport to marrow and other tissues

47
Q

what is Pernicious Anaemia?

A

Commonest cause of B12 deficiency in western populations

Autoimmune disease

Antibodies against:

  • intrinsic factor (diagnostic)
  • gastric parietal cells (less specific)

Malabsorption of dietary B12

Symptoms/signs take 1-2 years to develop (As stores of B12 in the body take a long time to run out)

48
Q

what is the treatment of megaloblastic anaemia?

A

Replace vitamin

B12 deficiency - B12 intramuscular injection, Loading dose then 3 monthly maintenance

Folate deficiency - Oral folate replacement, Ensure B12 normal if neuropathic symptoms

(Can precipitate worsening of neuropathic symptoms if you give folate and they have abnormal B12)

49
Q

what are some other causes of macrocytosis?

A

Alcohol (common cause)

Drugs - Methotrexate, Antiretrovirals, hydroxycarbamide

Disordered liver function

Hypothyroidism

Myelodysplasia

50
Q

Summay:

Anaemia -Morphological approach

A