Microanatomy 2 -Anaemia Flashcards

1
Q

What does blood consist of

A

Plasma (a watery ground substance)

Dissolved fibrinogen (which polymerises to form insoluble fibrin fibres during coagulation)

Circulating blood cells as its cellular component. The blood cells in peripheral blood are of three classes:

  • Leucocytes (white blood cells)
  • Platelets (thrombocytes)
  • Erythrocytes (red blood cells)
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2
Q

What are the three types of white blood cells

A

◦ granulocytes

◦ lymphocytes

◦ monocytes

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3
Q

what is the primary function of white blood cells

A
  • cytokines
  • immunoglobulins
  • complement proteins
  • phagocytosis
  • make antibodies
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4
Q

describe granulocytes

A

are named for their prominent and characteristic cytoplasmic granules as seen in standard blood films/smears (Romanowsky stain)

are characterised by the presence of nuclei with several lobes

are motile and phagocytic

can be divided on their cytoplasmic and nuclear appearances into neutrophils, eosinophils and basophils

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5
Q

how much percentage of white blood cells do neutrophils make up

A

account for a majority of leucocytes in the blood (approximately 60-70%)

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6
Q

what are neutrophils identified on

A

are identified on a Romanowsky stained blood film as cells with segmented nuclei (2-5 lobes) and fine, pinkish cytoplasmic granules

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7
Q

describe the role that the neutrophils play in the defence line

A

are highly phagocytic in their defensive role and in the removal of damaged tissue after injury (i.e. during acute inflammation)
- defence against most invading pathogenic organisms particularly bacteria

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8
Q

what are the types of granules do neutrophils have

A

have both primary (appear at the promyelocyte stage) and secondary (appear at the myelocyte stage) granules
- they are both lysosomal in origin

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9
Q

what is the difference between primary and secondary granules in neutrophils

A
  • primary granules contain myeloperoxidase, acid phosphatase and other acid hydrolases,
  • secondary granules contain collagenase, lactoferrin and lysozyme.
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10
Q

describe what neutrophil granules do

A

Enzymes within the granules act to kill and/or degrade the ingested microbe or debris. This process occurs by oxygen dependent (e.g. hydrogen peroxide and superoxides) and oxygen independent (e.g. acid pH, lactoferrin binds iron necessary for bacterial growth) pathways.

Regulatory substances are also secreted from granules and are involved in many inflammatory processes including mobilisation of inflammatory mediators, complement activation and cell adhesion.

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11
Q

when do neutrophils increase in number

A

increase in number in the blood during bacterial infection and inflammation (neutrophilia or neutrophil leucocytosis)

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12
Q

what organelles do neutrophils have

A
  • have few organelles for protein synthesis
  • are adapted for survival in anaerobic conditions (glycogen stores) and have a short lifespan usually dying following a single burst of activity.
  • Dead neutrophils as well as host tissue and foreign material liquified by the actions of released neutrophil enzymes are the main components of pus.
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13
Q

how much of circulating leucocytes does eosinophils make up

A

make up 1-4% of circulating leucocytes

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14
Q

how are eosinophils identified

A

are identified on a Romanowsky stained blood film as cells with segmented nuclei (usually bilobed) and red-orange granules

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15
Q

what defence are eosinophils involved In

A

are primarily involved in defence against parasitic infections, particularly helminths (parasitic worms) and protozoa.

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16
Q

what attracts eosinophils

A

ave lysosomal granules which contain cytotoxic compounds such as eosinophil cation, major basic protein and peroxidase as well as common lysosomal enzymes

have multiple biologic functions and contribute to a variety of immune defense mechanisms.

Eosinophil production and function are influenced by the cellular arm of the immune system (T-lymphocytes).

are proinflammatory cells that are capable of either protecting or damaging the host depending on the situation

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17
Q

describe how an eosinophil responds to an infection

A

e attracted by products released from basophils, mast cells, lymphokines from sensitised lymphocytes and allergy-related antigen/antibody complexes

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18
Q

how can an eosinophil modulate the allergic response

A

liberate substances that can neutralize mast cell and basophil products, thereby down modulating the allergic response

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19
Q

what is the proportion of basophils in the leucocyte population

A
  • less than 1 %
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20
Q

how are basophils identified

A

are identified on a Romanowsky stained blood film as cells with characteristic large dark purple cytoplasmic granules that often obscure the bilobed nucleus

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21
Q

what are the features of basophils that allow it to respond

A

have granules that contain histamine (vasoactive substance) and heparin (anticoagulant)

and mast cells (tissue equivalent of the basophil) function as mediators of inflammatory responses, especially those of immediate hypersensitivity reactions such as asthma, urticaria, allergic rhinitis and anaphylaxis

have membrane receptors for IgE. When IgE attaches to the receptor, the cell is activated and degranulation is initiated.

Degranulation releases enzymes that are vasoactive, bronchoconstrictive and chemotactic (especially for eosinophils). This release of mediators initiates the classical signs of immediate hypersensitivity.

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22
Q

what proportion of leucocytes does lymphocytes make up

A

make up 20-40% of circulating leucocyte

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23
Q

what are lymphocytes

A

are the immunologically competent cells that assist the phagocytes in the defence of the body against infection and other foreign invasion

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24
Q

what are the two main types of lymphocytes

A

B and T

B
- antibody mediate immunity

T
- cell mediated immunity

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25
Q

describe the lymphocytes

A
  • mostly have round, condensed nuclei typical of cells with little biosynthetic activity;
  • cytoplasm forms only a narrow rim around the nucleus.
  • A minority of lymphocytes are larger, mainly attributable to an increase in cytoplasm, and represent activated B cells and T cells or a small population of lymphocytes known as natural killer cells.
  • have the longest lifespan of any leucocyte with some cells living many years (e.g. memory cells).
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26
Q

describe the proportion of monocytes

A

make up 2-6% of circulating leucocytes

27
Q

describe the structure of monocytes

A

are the largest of the leucocytes and are of variable appearance.

  • The nucleus tends to be indented, bean-shaped or horseshoe-shaped,
  • with abundant blue-grey cytoplasm that may demonstrate vacuolation and fine granulation.
28
Q

what happens to the monocytes after 20-40 hours

A

after circulating in the blood for 20 – 40 hours, leave to enter the tissues where they mature into macrophages (histiocytes) and carry out their principal functions.
- Their extravascular lifespan may be as long as several months or even years. They may assume specific functions in different tissues e.g. Kupffer cells in the liver.

29
Q

what do macrophages do

A

o phagocytosing and destroying pathogens and cellular debris

o processing and presenting antigens to lymphoid cells; these antigen
presenting cells react principally with T cells

o producing cytokines which regulate and participate within cytokine and
growth networks governing haemopoiesis, inflammation and cellular
responses.

30
Q

what do platelets do

A
  • promote aggregation with other platelets
  • alter local blood flow
  • initiate the coagulation cascade and fibrin formation
  • encourage vascular repair
31
Q

what protein forms the cytoskeleton in red blood cells

A

have a cytoskeleton mostly formed by the protein spectrin which forms links with protein at the plasma membrane.

32
Q

what does the cytoskeleton do in the red blood cell

A
  • the cytoskeleton along with the water content of the cell determines its shape
33
Q

erythrocytes are characteristically…

A

are characteristically electron-dense when viewed in the electron microscope due to the iron atoms of haemoglobin.

34
Q

what can anaemia be caused by

A

It can be caused by reduced production or increased destruction or loss of erythrocyte

35
Q

what are the signs and symptoms of anaemia

A

nclude pallor, jaundice (haemolytic anaemias), fatigue, headaches, breathlessness and faintness.

36
Q

how can anaemia be classified

A
  • MCV
  • morphological appearance
  • or basic causes of anaemia
37
Q

what are the three classifications of anaemia

A
  • microcytic (small red cells with a reduced MCV)
  • normocytic (normal sized red cells with a normal MCV)
  • macrocytic (large red cells with a raised MCV).
38
Q

what are erythrocytes with varying sides referred to as

A

rythrocytes with varying sizes are referred to as having anisocytosis

39
Q

what are RBC with differing shapes referred as

A

differing shapes are referred to as having poikilocytosis

40
Q

what does hyochromic an normochormic mean

A

Red cells are also described as hypochromic or normochromic reflecting their level of pink staining and thus levels of haemoglobin.

41
Q

what are reticulocytes

A

Reticulocytes are immature red blood cells that have recently been released into the blood from the red bone marrow.
- They remaining presence of ribosomal RNA in these cells gives them a bluish tint in blood smears.

42
Q

what does elevated reticulocyte count mean

A

An elevated reticulocyte count indicates an increased rate of red cell production which can be clinically significant

43
Q

name some causes of anaemia

A
  • Impaired red cell production
  • acute blood loss
  • increased rate of red cell destruction (haemolytic anaemia)
44
Q

describe how impaired red cell production can cause blood loss

A
  • underproduction means less oxygen is carried round the body
  • may be due to decreased EPO production such as in chronic renal failure
  • or marrow failure
  • or marrow hypo responsiveness to erythropoietin
  • iron deficiency
  • thalassaemias
45
Q

what is thalassemia

A
  • it is an heridertary conduction
  • this is when there is an imbalance production of global chains which leads to precipitation of globing chains and ineffective erythropoiesis and anaemia
  • lack of haemoglobin production leads to the hypo chromic microcytic features
46
Q

what is the second most common cause of anaemia

A
  • anaemia of chronic disorders
47
Q

what do patients with anaemia of chronic disorders usually have

A
  • hypochromic microcytic anaemia

- or normochromic normocytic features

48
Q

what are the mechanisms that lead to anaemia of chronic disease

A
  1. iron stored in the macrophages is not released for erythropoiesis
    
2. there is an inadequate response to erythropoietin
    
3. red cells have a reduced life span
49
Q

what vitamins cause megaloblastic microcytic anaemia

A

B12 and folate

50
Q

what anaemia results from blood loss

A

normochromic, normocytic anaemia will result from an acute loss of blood

51
Q

what are the features of haemolytic anaemia

A

◦ Premature destruction of red cells

◦ Accumulation of the products of haemoglobin catabolism

◦ An increase in erythropoiesis in the blood marrow leading to reticulocytosis (increased numbers of reticulocytes) 


◦ The haemolytic anaemias can be classified into inherited and acquired

52
Q

what are the three forms that cause inherited haemolytic anaemia

A

forms are usually due to intrinsic cells defects, such
(a) membrane abnormalities e.g. hereditary spherocytosis and hereditary
 elliptocytosis


(b) defects in red cell metabolism e.g. reduced glutathione deficiency due to
 glucose-6-phosphate dehydrogenase (G6PD) deficiency causing increased sensitivity to oxidant stress

(c) abnormal haemoglobin production e.g. a structurally abnormal haemoglobin
 such as sickle cell anaemia (HbSS) or reduced globin chain synthesis 
(thalassaemia)

53
Q

what do the acquired form of haemolytic anaemia arise from

A

Acquired forms arise from actions of extrinsic factors such as pathogens, poisons, physical trauma or antibodies.

54
Q

what do spherocytes appear like in blood films

A

Spherocytes appear in blood films as normochromic erythrocytes without the usual central pallor

55
Q

what is sickle cell disease

A

A common hereditary haemoglobinopathy, sickle cell anaemia is caused by a haemoglobin gene variant that codes for the production of haemoglobin with abnormal structure.

56
Q

describe what sickle cell disease does to haemoglobin

A

the haemoglobin (HbS) undergoes aggregation and polymerisation

57
Q

how much does sickle cell disease shorten the red blood cell by

A

Red cell survival is shortened from 120 days to approximately 20 days.

58
Q

what are the two clinically relevant fragmentation for haemolytic anaemias

A

wo clinically relevant fragmentation haemolytic anaemias are those associated with cardiac valve prostheses and those associated with the narrowing or obstruction of vessels (microangiopathic haemolytic anaemia)

59
Q

How can prosthetic valves cased harm to red blood cells and haemolytic anaemia

A

Prosthetic valves cause damage to red blood cells through shear stresses produced by turbulent blood flow and abnormal pressure gradients.

60
Q

what is microangiopathic haemolytic anaemia associated with

A

Microangiopathic haemolytic anaemia associated with a variety of disorders (i.e. fibrin deposition in small vessels associated with disseminated intravascular coagulation, malignant hypertension, systemic lupus erythematosis, thrombotic thrombocytopenic purpura (TTP), haemolytic-uremic syndrome (HUS) and disseminated cancer) produces mechanical damage to red blood cells by squeezing them through abnormally narrow vessels

61
Q

where is the bone marrow found

A

bone marrow is found in the cancellous bone

62
Q

what does red bone marrow contain

A

contains a reservoir of pluripotent haemopoietic stem cells which give rise to the lymphoid and myeloid (forming granulocytes, monocytes, erythrocytes and megakaryocytes) cell lineages.

contains sinusoidal capillaries forming the vascular compartment and running between islands of haemopoietic cells (the haemopoietic compartment)

contains stromal cells which provide a unique microenvironment in which the ordered proliferation and differentiation of blood precursor cells occurs and macrophages which scavenge extruded nuclei of red cell precursors, malformed cells and excess cytoplasm.

63
Q

how can bone marrow be studied

A
  • can be studied in smears of aspirates or biopsies.

- Relative proportions of cells types in bone marrow are almost always altered in diseases of bone marrow and blood

64
Q

How is a bone marrow aspirate obtained

A

Aspirates are obtained through a needle positioned usually into the posterior iliac crest (pelvis) or sternum (obviously more risky).