4.01 - Always Tired - Anaemia

Front 1

which hormone stimulates the maturation of red blood cells?

Back 1

erythropoietin

Front 2

what is the lifespan of a RBC?

Back 2

120 days

Front 3

how is increased production of RBCs by the marrow achieved?

Back 3

expansion of the volume of red marrow and by shortening of transit time for red cell maturation

Front 4

with acute blood loss, what effect is there on platelets and WBCs?

Back 4

there may be a reactive thrombocytosis and leukocytosis

Front 5

what deficiency is the result of chronic blood loss?

Back 5

iron

Front 6

what are the last cells capable of division in the erythroid line?

Back 6

polychromatophilic erythroblasts

Front 7

what are the last cells of the erythroid line that can synthesise haemoglobin?

Back 7

reticulocytes

Front 8

what shape are erythrocytes?

Back 8

biconcave discs

Front 9

t/f... erythrocytes do not have organelles

Back 9

true

Front 10

which cells are the last in the erythroid line to have a nucleus?

Back 10

normoblasts

Front 11

where does haemopoiesis take place in the foetus?

Back 11

in the liver and spleen up to 7 months gestation and in the bone marrow after that

Front 12

what does the haemopoietic stem cell look like?

Back 12

small to intermediate sized lymphocyte

Front 13

t/f... commitment to a cell lineage is reversible

Back 13

true, but only under very specific circumstances with the correct factors (and only very recently)

Front 14

what is the source of erythropoietin?

Back 14

kidney

Front 15

what metals are required for normal haemopoiesis?

Back 15

iron, manganese, cobalt

Front 16

which vitamins are required for normal haemopoiesis?

Back 16

B12, folic acid, C, E, B6, thiamine, riboflavin, pantothenic acid

Front 17

what is the most common cause of anaemia?

Back 17

iron deficiency

Front 18

what is the laboratory hallmark of iron deficiency?

Back 18

microcytosis

Front 19

what is the definition of microcytosis?

Back 19

mean corpuscular volume less than 80 femtolitres

Front 20

what is the best measurement of overall iron stored in the body?

Back 20

serum ferritin

Front 21

which deficiencies result in megaloblastosis?

Back 21

vitamin B12 and folate

Front 22

hypersegmented neutrophils are a feature of which type of anaemia?

Back 22

megaloblastic anaemia

Front 23

what is the most common cause of macrocytosis?

Back 23

excess alcohol consumption

Front 24

which deficiency can cause profound neurological damage?

Back 24

Vitamin B12

Front 25

what is Vit B12 deficiency most commonly caused by?

Back 25

poor absorption from the bowel (often associated with pernicious anaemia)

Front 26

which cells are destroyed by antibodies in pernicious anaemia?

Back 26

gastric cells

Front 27

what substance is secreted by gastric cells?

Back 27

intrinsic factor

Front 28

name two non-immune causes of Vit B12 deficiency

Back 28

surgical removal of stomach or terminal ileum, poor diet lacking in animal products, proton pump inhibitor drugs

Front 29

where does folic acid absorption occur?

Back 29

jejunum

Front 30

which deficiency affects the peripheral nervous system only?

Back 30

folate

Front 31

Which two haematological conditions are associated with reduced haemoglobin concentration of the erythrocytes and are characterised by microcytic hypochromic erythrocytes?

Back 31

Iron deficiency and thalassaemia

Front 32

What is the best screening test for iron deficiency?

Back 32

serum ferritin

Front 33

What increases the secretion of erythropoietin?

Back 33

Fall in arterial oxygen tension, sensed by peritubular renal cells

Front 34

What is the term for the shortening of the lifespan on RBCs?

Back 34

haemolysis

Front 35

Which two conditions result in rapid falls in haemoglobin concentration?

Back 35

haemolysis and blood loss anaemia

Front 36

What are the clinical features of haemolysis?

Back 36

scleral jaundice, splenomegaly, increased reticulocytes, elevated LDH, asbence of serum haptoglobin, haemosiderin in urine

Front 37

What are some causes of haemolytic anaemia?

Back 37

hereditary spherocytosis, G-6-PDH deficiency, sickle cell anaemia, thalassaemia, immune disorders

Front 38

Where is haptoglobin produced?

Back 38

liver

Front 39

How does B12 deficiency result in neurological deficits?

Back 39

Causes Subacute Combined Degeneration of the Spinal Cord - B12 is made for fatty acid synthesis, and in deficiency fatty deposits are laid down very patchily within the myelin (demyelination) and APs are slowed

Front 40

Which two pathways in the white matter of the spinal cord are affected by B12 deficiency?

Back 40

the dorsal columns and the lateral corticospinal tract

Front 41

t/f... subacute combined degeneration of the spinal cord affects the transmission of pain information in the spinal cord

Back 41

false, pain travels in the lateral spinothalamic pathways which are not involved in subacute combined degeneration

Front 42

what is the prevalence of undernutrition in community living?

Back 42

5-12%

Front 43

what is anaemia?

Back 43

reduction in red cell number, haemoglobin or haematocrit

Front 44

why does haemoglobin reduce in pregnancy?

Back 44

haemodilution - increase in plasma volume is greater than increase in rbc

Front 45

what is the normal range for % reticulocytes in a blood film?

Back 45

0.5% - 1.5%

Front 46

what fraction of a red blood cell is normally central pallor?

Back 46

1/3

Front 47

t/f... reticulocytes contains some RNA

Back 47

true

Front 48

what is required for haemoglobin synthesis?

Back 48

haem synthesis, globin synthesis, iron

Front 49

what is required for red cell production?

Back 49

erythropoietin, vit B12, folic acid, metals

Front 50

where is erythropoietin produced?

Back 50

kidney (and to a lesser extent the liver)

Front 51

what effect does hypoxia have on the production of EPO?

Back 51

production is increased by hypoxia (related to HIF)

Front 52

what are the haematinics?

Back 52

iron, B12, folate

Front 53

what happens to senescent RBCs?

Back 53

removed to the spleen by macrophages

Front 54

what percentage of RBCs need to be replaced daily to maintain steady state?

Back 54

1%

Front 55

t/f... cardiac output increases in response to anaemia

Back 55

true

Front 56

list the symptoms of anaemia

Back 56

tiredness, headaches, dizziness, SOB, palpitations, angina (with pre-existing heart disease)

Front 57

what are the signs of anaemia?

Back 57

pallor (conjunctival, palmar crease), cardiac decompensation (tachycardia, postural hypotension, CCF)

Front 58

what effect does anaemia have on viscosity of blood?

Back 58

anaemia reduces viscosity of blood

Front 59

what is the effect of reduced O2 delivery to tissues on blood vessels?

Back 59

dilatation (except at lungs)

Front 60

which deficiency leads to both peripheral and central neurological signs?

Back 60

B12

Front 61

will deficiency of the haematinics be associated with a low or high reticulocyte count?

Back 61

low

Front 62

will haemolysis be associated with a low or high reticulocyte count?

Back 62

high

Front 63

list some causes of haemolysis

Back 63

immune attack on red cells (autoimmune, drugs e.g. methyldopa, alloimmune e.g. incompatible red cell transfusion, Rh disease), abnormal red cell membrane (HS), abnormal red cell metabolism (G6PDH deficiency), mechanical (malfunctioning prosthetic heart valve, DIC, malignancy)

Front 64

list 3 causes of macrocytic normochromic anaemia

Back 64

B12 deficiency, folate deficiency, myelodysplasia, alcohol consumption

Front 65

what is the appearance of the rbc on a blood film from a patien with anaemia from marrow suppression/aplasia?

Back 65

normocytic, normochromic

Front 66

what type of anaemia do defects in Hb synthesis cause?

Back 66

microcytic hypochromic

Front 67

what is the normal size of a RBC compared to a lymphocyte?

Back 67

RBC should be size of lymphocyte nucleus

Front 68

What do target cells indicate?

Back 68

hypochromia - excess membrane relative to haemoglobin (found in thalassaemia, asplenia, liver disease, severe iron deficiency)

Front 69

How many lobes does a hypersegmented neutrophil have?

Back 69

>5

Front 70

What do oval macrocytes indicate?

Back 70

B12 or folate deficiency (megaloblastic anaemia)

Front 71

When does rouleaux occur?

Back 71

increased plasma proteins usually from inflammation e.g. myeloma

Front 72

which leakaemia is associated with Auer rods?

Back 72

AML

Front 73

t/f... most people with anaemia receive a transfusion

Back 73

false, the only indication for transfusion is tissue hypoxia (severe anaemia)

Front 74

what is the commonest form of anaemia?

Back 74

iron deficiency

Front 75

what are the two stores of iron in the body?

Back 75

ferritin, haemosiderin

Front 76

t/f... there is no effective excretion mechanism for iron

Back 76

true

Front 77

how is iron balance controlled?

Back 77

iron absorption

Front 78

what regulates iron absorption?

Back 78

mucosal cells of proximal small intestine

Front 79

what are the two pathways for dietary iron absorption?

Back 79

iron attached to haem, iron in ferrous form

Front 80

t/f... haem/ferrous iron absorption is enhanced by ascorbate and meat and inhibited by phytates, bovine milk, tea and coffee

Back 80

false, this is true for non-haem/ferric iron absorption as it is insoluble (haem iron absorption is unaffected by composition of diet)

Front 81

what assists solubilisation, mucin binding and reduction of ferric iron to the ferrous form?

Back 81

acid (e.g. gastric juice, ascorbic acid)

Front 82

What enzyme reduces ferric iron to ferrous form?

Back 82

Dcytb (duodenal cytochrome b1)

Front 83

What is the role of DMT1 (divalent metal transporter) in dietary iron absorption?

Back 83

apical uptake at duodenum

Front 84

What transfers iron into the plasma from the enterocyte?

Back 84

ferroportin (transfer is facilitated by hephaestin)

Front 85

What is hepcidin?

Back 85

peptide hormone secreted by liver

Front 86

what is the function of hepcidin?

Back 86

decreases functional activity of ferroportin, reducing Fe leaving a cell

Front 87

how does intestinal absorption of Fe relate to liver hepcidin expression?

Back 87

absorption varies inversely with expression

Front 88

what is the sole physiologic means of iron transport?

Back 88

transferrin

Front 89

what is the average daily loss of iron in men and non-menstruating women?

Back 89

1 mg/day

Front 90

what is the average daily iron loss in menstruating women?

Back 90

2 mg/day

Front 91

how much iron do pregnant women lose every day?

Back 91

3.5 mg/day

Front 92

what is the most important lab marker of iron deficiency?

Back 92

serum ferritin

Front 93

what effect does iron deficiency have on serum transferrin?

Back 93

raised

Front 94

what percentage of oxygen in the blood is dissolved?

Back 94

1.5%

Front 95

list 4 factors that will decrease oxygen affinity for Hb

Back 95

increased PCO2
acidosis
increased temp
increased 2,3-DPG

Front 96

t/f... reduced affinity of oxygen for Hb is equivalent to a shift to the left of the O2-Hb curve

Back 96

false, it is a shift to the right

Front 97

what is the Bohr effect?

Back 97

oxygen carrying capacity of Hb at a particular PO2 is decreased by increased PCO2

Front 98

what is the affinity of CO for Hb compared to oxygen?

Back 98

200 times

Front 99

what type of anaemia occurs in thyroid disease?

Back 99

macrocytic

Front 100

what volumes define microcytic, normocytic and macrocytic?

Back 100

microcytic: <80 fl
normocytic: 80-99 fl
macrocytic: >99 fl

Front 101

what type of anaemia occurs with impaired DNA synthesis?

Back 101

megaloblastic (vit B12 or folate deficiency)

Front 102

list some blood film changes in megaloblastic anaemia

Back 102

oval macrocytes, aniso/poikilocytosis, hypersegmented neutrophils, may have low WCC and low platelets

Front 103

how long do body stores of vitamin B12 last?

Back 103

3-4 years

Front 104

what is vitamin B12 bound to in the plasma?

Back 104

transcobalamin (TC II)

Front 105

where is vitamin B12 absorbed?

Back 105

terminal ileum

Front 106

what secretes intrinsic factor?

Back 106

gastric parietal cells

Front 107

What does B12 bind to in the stomach to travel to the terminal iluem for absorption?

Back 107

intrinsic factor

Front 108

Which columns of the spinal cord are affected in B12 deficiency?

Back 108

posterior and lateral

Front 109

Which peripheral fibres are affected in B12 deficiency?

Back 109

peripheral sensory nerves

Front 110

t/f... inadequate intake is a common cause of vitamin B12 deficiency

Back 110

false, it is a very rare cause (only in true vegans)

Front 111

What is the most common cause of vitamin B12 deficiency?

Back 111

malabsoption due to inadequate intrinsic factor or disorders of terminal ileum

Front 112

What is pernicious anaemia?

Back 112

severe lack of intrinsic factor due to autoimmune disease affecting gastric parietal cells

Front 113

Is pernicious anaemia more common in men or women?

Back 113

women (M:F 1:1.6)

Front 114

Which antibody is highly specific for pernicious anaemia?

Back 114

anti-intrinsic factor (found in 95% patients)

Front 115

How long do the body stores of folate last?

Back 115

3-4 months

Front 116

Where is the body's store of folate?

Back 116

liver

Front 117

Where is folic acid absorbed?

Back 117

proximal jejunum

Front 118

t/f... folic acid is absorbed via specific receptors

Back 118

false, folic acid is absorbed via concentration dependent diffusion (B12 is absorbed via specific receptors)

Front 119

When is there an increased need for folic acid?

Back 119

pregnancy, prematurity, haemolysis, malignancy (anything causing increased cellular proliferation)

Front 120

Which disease causes malabsorption of folate?

Back 120

Coeliac disease

Front 121

Name some antifolate drugs.

Back 121

methotrexate, anticonvulsant, trimethoprim, alcohol

Front 122

Which measure of folate tests body stores not just recent intake?

Back 122

red cell folate

Front 123

Name three situations in which serum folate will be raised.

Back 123

severe vitamin B12 deficiency
folic acid therapy (methotrexate)
sample haemolysed

Front 124

When might red cell folate be falsely normal?

Back 124

blood transfusion
increased reticulocytes

Front 125

When will the peak reticulocyte response be observed after starting therapy for megaloblastic anaemia?

Back 125

6-7 days

Front 126

How long will it take after beginning treatment for megaloblastic anaemia for the bone marrow to be normoblastic?

Back 126

48 hours

Front 127

At what rate will the Hb rise after commencing treatment for megaloblastic anaemia?

Back 127

Hb should rise by 10g/L per week

Front 128

t/f... B12 deficiency will cause a deficiency in homocysteine

Back 128

false, it causes a rise

Front 129

What is used to treat Methaemoglobin?

Back 129

When Haem has Fe3+/ferric iron (e.g. from high oxidants in broadbeans, drugs etc), it is reduced to the Fe2+/ferrous iron by IV methylene blue.

Front 130

t/f... folate should always be given before B12 in deficiencies where both are to be given

Back 130

false, if folate is given first, B12 supplies can be converted into methylcoalbumin, and won't be able to take place in fatty acid metabolism, facilitating subacute degeneration of the spinal cord

Front 131

Describe haematopoiesis and where it takes place.

Back 131

The formation of cells for the blood, these include lymphoid cells (T, B, NK cells) and myeloid cells (granulocytes, monocytes, megakaryocytes, erythrocytes).

It begins in the yolk sac, then migrates to the liver and spleen, then the bone marrow during gestation. As an adult, in times of severely increased demand, haematopoietic centres can be re-established in the liver, spleen and lymph nodes.

Front 132

What ability is missing in the division of neoplastic haematopoietic cells?

Back 132

Neoplastic haematopoietic cells are able to self renew but are unable to differentiate into further cell types.
Coaxing cells into differentiation can be a form of treatment for some cancer types e.g retinoic acid in APML.

Front 133

What is erythropoietin, what does it act on, where is it made, and when is it released?

Back 133

Erythropoietin (EPO) is a cytokine responsible for maturation of all red cells by inhibiting apoptosis. It also inhibits hepcidin, and so enhances Iron absorption.
EPO binds to EPO to elicit its actions. EPO-R are not present in the earliest RC progenitors, but are in subsequent nucleated progenitors after and are last seen in erythroblasts.
It is made by peritubular cells in the kidney (and cells in the liver to a smaller extent) in response to low O2.

Front 134

What myelolid cell lineage do the following factors cause to clonally expand?
1) ILF
2) GM-CSF
3) G-CSF
4) M-CSF
5) EPO
6) TPO

Back 134

1) All myloid lineage cells in early stages
2) Neutrophils, macrophages, eosinophils
3) Neutrophils alone
4) Macrophages alone
5) Erythrocytes alone
6) Megakaryocytes alone

Front 135

Name 3 important factors needed for haematopoiesis.

Back 135

Iron, Magnesium, cobalt
B1 (thiamine), B2 (riboflavin), B5 (pantothenic acid), B6 (PLP), B9 (folic acid), B12 (cobalamin), C, E
Amino acids
Hormones
Cytokines - ILFs, CSFs
Stromal cells
MicroRNAs (downregulate gene transcription)

Front 136

Describe how most bone marrow replacements are done currently (2012)?

Back 136

Peripheral blood bone progenitor collection - cells are coaxed out using niche factors usually secreted by stromal bone marrow cells (CSFs, IL4). Blood is then collected and put through leukophoresis to siphon out WBC. These can be stored on elastic beds (physically similar to bone marrow) while the patient is irradiated, then over 28 days given progenitor cell transfusions.

Front 137

Describe the structure of haemoglobin?

Back 137

4 polypeptide globin chains, each around a central haem bound to a Fe2+ (Fe3+ = methaemoglobin and is inefficient). The haem group is non-protein, and is known as a porphyrin.

Front 138

What tests/investigations can you use to detect the presence of a haemolytic anaemia?

Back 138

Low levels of free haptoglobin (usually binds to free haemoglobin in plasma).
High LDH (used in RC glycolysis, realeased when they lyse)
High bilirubin (what haem breaks down into)
Increased reticulocytes (to keep up with increased demand)
Haemosiderin in urine.
Heinz bodies from denatured Hb in oxidative stress.