L27 Disorders of Blood

Question 1

how would you describe a decrease/increase in :

RBC
WBC
platelets

Answer 1

Dec RBC = anaemia

Dec WBC = leukopenia

Dec patelets = thrombocytopenia

Inc RBC = erythryocytosis

Inc WBC = leucocytosis

Inc platelets = thrombocytosis or thrombocythemia

Question 2

what are the major causes of thrombosis?

Answer 2

atherosclerosis
cancer
immobilisation
surgery
hypercoagulability (iinhibitor (PC, PS, AT) deficiencies)
thrombocythaemia (high platelet)

Question 3

how are haemotological malignancies classified?

Answer 3

blood cell linage:
- myeloid neoplasm or lymphoid neoplasm

location:
- leukaemia (blood) or lymphoma (lymph nodes)

whether it is acute (weeks/-blasts) or chronic (years/mature cells)

Question 4

what is neoplasia and what are the 2 classes of genes implicated?

Answer 4

uncontrolled cell growth

Oncogenes: directly causative of cancer – includes growth factors and their receptors, DNA binding proteins

Tumour suppressor genes: loss of suppressor activity leads to cancer

Question 5

what are myeloid malignancies?

Answer 5

heterogeneous disorders characterized by uncontrolled proliferation and/or blockage of differentiation of abnormalmyeloidprogenitor cells.

Question 6

what may myeloid neoplasias be caused by?

Answer 6

Polycythaemia (inc RBC)

Thrombocythaemia (inc platelets)

Myelofibrosis (inc megakaryocyte)

Chronic myeloid leukaemia (increased granulocytes – Philadelphia chromosome 9 + 22 translocation)

Question 7

what is leukaemia and how may levels in the blood change? symptoms?

Answer 7

Accumulation of white blood cells in the bone marrow and blood

bone marrow failure

dec RBC, dec platelets, but inc WBC. if disease advances, WBC dec due to BM failure

Blood hyperviscosity due to inc white cells causing respiratory or neurological symptoms
Infection if dec white cells
Tiredness/anaemia
Bleeding

Question 8

what is lymphoma?

Answer 8

T or B lymphocyte neoplasia affecting lymph nodes.

can be hodgkin (characterised by presence of Reed-Sternberg cells, usually upper body)

or non-hodgkin (linked to epstein-barr virus, can affect lymph nodes all over body)

Question 9

how low do haemoglobin levels have to be to be classified as anaemia and what are the common symptoms?

Answer 9

men = < 13.5 g/dL
women = < 11.2 g/dL

tiredness
pallor
fainting
tachycardia
shortness of breath

Question 10

what is the difference between acute and chronic anaemia?

Answer 10

acute - caused by large blood loss

chronic - vol of blood loss exceeds capability of haematopoiesis of bone marrow eg peptic ulcer

both are normocytic anaemia - cells are normal, but not enough of them

Question 11

what are Colony-stimulating factors (CSFs) and lymphokines?

Answer 11

Colony-stimulating factors (CSFs) = involved in haemopoiesis of myeloid cells inc RBCs

lymphokines = involved in haemopoiesis of ,ymphocytes + NK cells

Question 12

where is EPO produced?

Answer 12

Epo is produced by interstitial fibroblasts in the kidney, hence why renal disease can lead to anaemia

Question 13

which type of anaemia does iron deficiency cause and what can be the causes of this deficiency?

Answer 13

reduced haem production = microcytic anaemia (pale + small RBC)

causes:
diet
blood loss
infection (hookworm)
growth spurts, pregnancy

Question 14

what does hypochromic, anisocytosis, and poikilocytosis mean?

Answer 14

hypochromic = less haemoglobin in each RBC

anisocytosis = variation in size

poikilocytosis = variation in shape

Question 15

how does vit B12 and folate influence anaemia?

Answer 15

Vit B12 and folate involved in DNA replication

Deficiency of either causes problems with mitosis (cell division) of the proerythroblast

This causes megaloblastic or macrocytic anaemia (large RBCs)

Vit B12 deficiency mostly caused by reduced absorption

Folate deficiency may be caused by poor nutrition, alcoholism, malabsorption, certain drugs (anti-epileptics/antibiotics)

Question 16

what is megaloblastic anaemia?

Answer 16

caused by folate or Vitamin B12 deficiency, leads to larger than normal RBCs and includes the formation of macroovalocytes (thin arrows) and also may lead to hypersegmented neutrophils (thick arrow, due to disordered nuclear maturation).

Question 17

what is haemolytic anaemia?

Answer 17

Due to increased RBC destruction

RBC lifespan down from 120 to as little as 20 days

Bone marrow unable to replace sufficient RBCs

Acquired (malaria, sepsis)

Inherited (G6P dehydrogenase, Autoimmune Hemolytic Anemia)

Question 18

what are some differences/examples of immune and non-immune haemolytic anaemia?

Answer 18

Immune:
Haemolytic syndrome in the newborn (Rh)
Autoantibodies
Complement

Non-immune:
Drug-induced
Snake venom
Mechanical (heart valves)
Infections (malaria, septicaemia)

Question 19

which RBC cytoskeletal defect causes anaemia?

Answer 19

Mutations in a or b spectrin -> Hereditary spherocytosis

Cytoskeleton of RBC is made of spectrin which makes them able to be flexible. With damaged or no spectrin the RBC are a spherical shape and are unable to squeeze through places

Question 20

which RBC enzyme defect causes anaemia?

Answer 20

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, involved in NADPH metabolism

Question 21

which haemoglobin defects cause anemia?

Answer 21

sickle cell

thalassaemia

Question 22

what is the cause and effect of sickle cell disease?

Answer 22

cause:
Mutation in the Hb b globin gene Glu 6–>Val

Polymerisation of Hb, distorting RBC

Widespread in Africa (Carribean), Middle East, India and Med

effect:
“Sickling” of RBC (particularly in homozygous disease)

Sickle cell crisis due to blockage of microvasculature

Heterozygosity confers protection against malaria

Question 23

what is thalassaemia?

Answer 23

Microcytic anemia

Defects in either the alpha or beta chains of hemoglobin, leading to ineffective erythropoiesis and hemolysis

a-thalassemia:
Prevalent in Africa, Mediterranean, Middle East, Asia

b-thalassemia:
Prevalent in Mediterranean, South East Asia, India, PakistaN