RBC/WBC Detail Flashcards

1
Q

What are leucocytes and what are the types?

A

White cells which defend body against infection and participate in immune response. Are of 5 types in blood: 3 known as granulocytes as cytoplasm contains granulocytes, lymphocytes and platelets derived from megakaryotes.

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2
Q

What are the different granulocytes and how are they identified?

A

Depending on colour of granules in cytoplasm in stained blood film. Neutrophils = small lilac. Eosinophils = large orange. Basophil = large purple. Have lobulated or polymorphous nuclei so called polymorphonuclear leucocytes. Function mainly in tissue and reach by migrating through endothelium of capillary.

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3
Q

What are neutrophils and how do they reach pathogen target?

A

Neutrophils are phagocytic cells that respond to chemotactic stimuli by migrating to site of infection, inflammation or death and spend 7 hours in circulation. Process involves rolling along endothelium, adhering to specific endothelial receptors, diapedesis (moving through capillary wall) and migrating through tissue in response to chemotaxins.

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4
Q

How do neutrophils act within the tissue?

A

Pseudopodia flows around particles followed by fusion where bacterium enclosed in phagocytic vacuole in cytoplasm and garnules of neutrophil containing proteolytic enzyme and myeloperoxidase discharge into vacuole. Proteolysis of contents occur.

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5
Q

What is the function of eosinophils?

A

Defence against parasitic infection. Less efficient than neutrophil against bacteria. Also have unwanted actions when involved in allergic reaction.

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6
Q

What is the function of basophils?

A

Defence against parasite and allergic reactions.

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7
Q

Describe lymphocytes and different types

A

Lymphocytes are smaller than granulocytes and some contain cytoplasmic granules. Circulating lymphocytes look very similar to one another but are mainly of three lineages: B-cells, T-cells and NK cells. B-cells of bone marrow origin and migrate to lymph nodes and lymphoid tissue upon maturation. T-cells of bone marrow origin but migrate to thymus where they mature and then migrate to lymphoid tissues. NK cells part of body’s innate immune response.

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8
Q

How do B-cells act?

A

Exposed to antigen-presenting cells in lymphoid tissue where they undergo somatic mutation and cells most capable of recognising antigen survive and mature into memory B-cell and plasma cell. Exit from bloodstream through high endothelial venules of lymph nodes and post-capillary venules of other tissues.

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9
Q

How do T-cells act?

A

Diverse subsets of T-cells where some function in cell-mediated response, binding to and damaging antibody-coated cells or modulate function of B cells acting as helper or suppressor cells, activate macrophages and attract+activate neutrophils. Some have cytotoxic effect without prior recognition of antigen and subset of T-cells also has regulatory function, maintaining immune tolerance.

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10
Q

What are monocytes?

A

Largest cell present in blood, have lobulated nucleus and plentiful cytoplasm. Mature into macrophages or histiocytes in tissues (reticuloendothelial system) which phagocytose and kill microbes and break down cell debris. Present antigens to lymphocytes. Secrete cytokines enhancing inflammatory response and growth factors, promoting neutrophil and monocyte production. Destroy parasites and red blood cells at end of life, storing haemoglobin to recycle.

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11
Q

What are platelets?

A

Small particles formed by fragmentation of cytoplasm of megakaryocytes. Function in primary haemostatic response, forming platelet plug at site of small vessel injury. When activated, expose altered phospholipid on surface interacting with coagulation factors to promote blood coagulation at site of tissue injury. Survive for 10 days.

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12
Q

What cells circulate in bloodstream?

A

In healthy subjects, only platelets and end cells of the myeloid and erythroid lineages are released into bloodstream. In erythrocyte lineage, only reticulocyte and polychromatic erythrocyte are released.

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13
Q

What is a reticulocyte?

A

Formed from nucleated erythroblast which squeezes through endothelium leaving nucleus behind and still contains ribosomes (stains blue on standard stain due to high RNA content). Carries on synthesising haemoglobin since it has ribosome which mature red cell doesn’t and in 1-3 days loses ribosomes, becoming mature. Remodels to hollowed out disc.

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14
Q

How is differentiation of stem cells and progenitor cells to specific cell lineages controlled? Where are E and T produced?

A

By cytokines: stem cell factor, erythropoietin (erythrocytes), thrombopoietin (megakaryocytes), G-CSF, and GM-CSF. E produced in kidney in hypoxic conditions, leading to earlier release of reticulocytes from bone marrow. T produced by liver and small amounts by bone marrow, upregulated in cases of infection, inflammation and iron deficiency.

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15
Q

What does thrombopoietin do?

A

Combines with specific receptor on cell membrane. Enhances survival+expansion of HSCs and promotes differentiation of these cells to megakaryocytes.

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16
Q

Where is G-CSF produced and what does it do?

A

Produced by fibroblasts, endothelial cells and macrophages. Increases neutrophil production, survival and activity while increasing their release from bone marrow.

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17
Q

Where is GM-CSF produced and what does it do?

A

Produced by lymphocytes and macrophages. Increases proliferation of progenitor cells, accelerates release and prduction in bone marrow of neutrophils and monocytes plus increases their activity.

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18
Q

How does haemopoeitic marrow change through life?

A

In adults, it is mainly in skull, sternum, ribs, vertebrae, upper sacrum, pelvis and proximal long bones. Extends more widely in children. However, red marrow can re-expand in adults should there be a need for more blood cells.

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19
Q

What is needed for haemopoiesis?

A

Iron, Folate, Vitamin B-12. Latter two needed for DNA Synthesis and hence required by rapidly proliferating tissue like bone marrow.

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20
Q

What is the difference between iron deficiency and iron depletion?

A

In deficiency, amount of iron available in tissues is inadequate for haemoglobin synthesis whereas in iron depletion, iron stores are reduced or absent but absorption is keeping up with demand.

21
Q

Why does B-12 and Folate deficiency lead to megaloblastic anaemia?

A

DNA synthesis needs dATP, dTTP, dCTP and dGTP. B12 and Folate needed for dTTP synthesis so when deficient, DNA can’t be replicated as no thymidine and hence new erythrocytes not made leading to anaemia.

22
Q

Describe haematopoietic lineages

A

Starts from multipotent haematopoietic stem cell - some differentiate into daughter cell lineages whereas others remain HSCs so pool not depleted. HSC gives rise to common myeloid progenitor and common lymphoid progenitor. Lymphoid progenitor gives rise to NK cell and small lymphocyte. Small lymphocyte can become T-cell or B-cell. Myeloid progenitor gives rise to megakaryocyte, erythrocyte, mast cell and myeloblast. Myeloblast gives rise to granulocytes and monocyte. Monocyte forms macrophage.

23
Q

How is B12 absorbed and what causes deficiency?

A

Parietal cells of stomach make intrinsic factor which binds to B12 and when this combo binds to receptor, they are absorbed into ileum. Causes of deficiency are when there is not enough in the diet, pernicious anaemia and malabsorption. Pernicious anaemia is an autoimmune disorder where IF or parietal cells are destroyed by antibodies.

24
Q

What happens at the end of a red blood cell’s life?

A

Macrophages of spleen detect old RBCs and destroy them, releasing globin and haem. Haem releases iron and bilirubin on breakdown. Iron is released to bone marrow while bilirubin take to liver and stored in gut until eventually excreted.

25
Q

What are the terms used to describe size of red blood cell? What is a variable range of sizes?

A

Microcytic = smaller RBCs or anaemia with smaller cells. Normocytic = normal RBCs. Macrocytic = larger than normal. Anisocytosis describes when there is variability in sizes.

26
Q

What are the different shapes of red blood cells? What is variable range in shapes?

A

Spherocytes, fragments, irregularly contracted cells, target cells, elliptocytes, sickle cells. Poikilocytosis describes more variation in shape than normal.

27
Q

What does colour of cells indicate?

A

Middle 1/3 of cell should be pale due to biconcave shape as less Hb in centre. Hypochromia describes a larger area of central pallor than normal and often goes with microcytosis. Due to lower Hb content and is a flatter cell. Hyperchromia describes a smaller area of central pallor than normal. These are thicker than normal or have abnormal shape. These are also called target cells and a result of obstructive jaundice, liver disease, haemoglobinopathies and hyposplenism. Polychromasia are cells with a blue tinge.

28
Q

How can age of cell be detected?

A

Immature RBCs are larger than normal RBCs and known as reticulocytes. Reticulocytosis is when there is increased presence of reticulocytes due to bleeding or red cell destruction.

29
Q

What are sickle cells?

A

sickle/crescent shaped, Hb S polymerizes, esp. when deoxygenated, HbS made when 2 abnormal B chains

30
Q

How are reference ranges derived?

A

Come from a defined reference population and is a 95% range. Samples collected from healthy volunteers with defined characteristics, analysed with instruments and techniques, statistically analysed to derive range.

31
Q

What affects normal?

A

Age, gender, ethnic origin, physiological status, altitude, nutritional status.

32
Q

What are appopriate statistical techniques?

A

Data with normal distribution looked at with mean and SD. Diff distribution can’t be analysed with that.

33
Q

What is anaemia? Describe mechanisms and types

A

Reduction in haemoglobin concentration below expected range for a healthy subject of same age and gender. Common mechanisms include: reduction in RBC production in bone marrow, blood loss, reduced survival of RBC in circulation, pooling of RBCs in enlarged spleen. Types include microcytic anaemia, normocytic anaemia and macrocytic anaemia.

34
Q

What is microcytic anaemia and what causes it?

A

Decrease in average cell size usually accompanied with hypochromia. Common causes are defect in haem synthesis (Fe deficiency, anaemia of chronic disease) or defect in globin synthesis (thalassemia, type depending on which chain affected.) Causes of iron deficiency are: increased blood loss (menstrual, hookworm), insufficient intake (malabsorption, Coeliac disease) and increased requirement (pregnancy, infancy, physiological)

35
Q

What is macrocytic anaemia and what causes it?

A

When average cell size is increased. May be due to abnormal haemopoeisis so red cell precursors generate Hb and other cell proteins but don’t divide normally. Megaloblastic erythropoeisis is when nucleus doesn’t mature but cell and cytoplasm continue to grow. Megaloblasts seen in bone marrow and shouldn’t be seen on blood film. Causes of this are: lack of B12 and folate, drugs interfering with DNA synthesis, liver disease+ethanol toxicity, recent major blood loss resulting in more reticulocytes, haemolytic anaemia.

36
Q

What causes normocytic anaemia?

A

Recent blood loss due to trauma; Failure in red cell production due to leukemia, bone marrow failure, early stage iron deficiency; Pooling of RBCs in spleen due to hypersplenism resulting from liver cirrhosis or splenic sequestration as in SCA.

37
Q

What is polycthaemia?

A

Too many RBCs in circulation due to blood doping or transfusion, increased erythropoeitin, renal tumour, polycthaemia vera (bone marrow disorder). Leads to myeloproliferative neoplasm or thick blood so drugs given to reduce bone marrow producing RBCs.

38
Q

What is leucocytosis and leucopenia?

A

cytosis is too many white cells while penia is reduction.

39
Q

What causes neutrophilia?

A

Infection (esp bacterial), inflammation, infarction, myeloproliferative neoplasms (cancer of too many WBCs), sudden increase after exercise as they go back into circulation from tissues, pregnancy and admin of corticosteroids.

40
Q

What accompanies neutrophilia?

A

Left shift and toxic changes. Left shit is when precurors of neutrophils such as band forms come into circulation - increase in non-segmented neutrophils. Toxic granulation is the heavy granulation of neutrophils.

41
Q

What causes neutropenia?

A

Can happen after chemo/radiotherapy, autoimmune disorders, bacterial infections, some viral infections, drugs such as anti-psychotic or anti-convulsants or anti-malarial. Can sometimes be benign ethnic neutropenia in people of Afro-Caribbean origin. If count very low, at increased risk of serious infection so need urgent treatment with IV antibiotics.

42
Q

What causes hypersegmented neutrophils?

A

Normal should have 3-5 segments or lobes. Usually due to lack of folic acid/B12 and causes megaloblastic anaemia. Marker is nucleo-cytoplsmic dissociation where nucleus doesn’t mature.

43
Q

What causes lymphocytosis?

A

Can be temporary response to viral infection but if chronic or long-term, could be CML. Can be due to whooping cough (Bordella pertussis) which is especially big cause in kids. Could also be Epstein-Barr Virus (causes glandular fever) where lymphocytosis present with atypical lymphocytes.

44
Q

What causes lymphopenia?

A

Too few lymphocytes. Most are T-cell CD4+ cells so common causes are HIV, chemotherapy, radiotherapy, steroids, temporarily during severe infection.

45
Q

What causes monocytosis?

A

Too many monocytes. Infection (esp bacterial), inflammation, some leukaemias

46
Q

What causes eosinophilia?

A

Allergy, parasitic infection, asthma, drugs, leukaemia

47
Q

What causes basophilia?

A

Rare, seen in case of some leukaemia

48
Q

What is leukaemia and what are the causes?

A

Leukaemia is cancer of the blood or bone marrow diseases. Results from series of mutations in single lymphoid or myeloid stem cell – mutations lead progeny of cell to show abnormalities in proliferation, differentiation or cell survival – leads to steady expansion of leukemic clone

49
Q

How are leukaemias classified and what are the types?

A

Chronic leukaemias behave in relatively benign way and take a long time. Acute leukaemias more malignant. Myeloid leukaemia affects granulocytic, erythrocytic, monocytic or megakaryocytic lineages. Lymphoid leukaemias affect B-cell, T-cell or NK cells. Four types are:

  1. Acute lymphoblastic leukaemia (ALL)
  2. Acute myeloid leukaemia (AML)
  3. Chronic lymphocytic leukaemia (CLL)
  4. Chronic myeloid leukaemia (CML