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MEH > Session 3 > Flashcards

Session 3 Flashcards

1
Q

What is haemopoiesis?

A

The production of blood cells.

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2
Q

Where does haemopoiesis occur?

A

Bone marrow

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3
Q

How does haemopoiesis location change from infancy to adulthood?

A

• Bone marrow extensive throughout the skeleton in
infant
• More limited distribution in adulthood, predominantly:
Pelvis, sternum, skull, ribs, vertebrae

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4
Q

How is haemopoiesis controlled

A

Controlled through combination of transcription factors, hormones and interaction with other non haemopoietic cell types such as endothelial cells.

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5
Q

What can the haemopoietic stem cell do?

A

• Has the greatest power of self-renewal compared to any other adult tissue
• It can renew itself, and ….can differentiate to a variety of specialised cells ….dependent on
different stimuli
• Can mobilize out of the bone marrow into circulating blood
• Can undergo programmed cell death, apoptosis

Resides in bone marrow

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6
Q

What are the sources of Haemopoietic stem cells?

A
  • Aspiration of bone marrow - rarely done now

* GCSF mobilised stem cells in the peripheral blood (collected by leucopharesis

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7
Q

What is the reticuloendothelial system?

A

The reticuloendothelial system is a network of cells located throughout the body and is part of the larger immune system. The role of this system is to remove dead or damaged cells and to identify and destroy foreign antigens in blood and tissues. The cells which make up this system are phagocytic and include monocytes in blood and different types of macrophages in various tissues e.g.:
Macrophage type - Tissue
Kupffer cell - Liver
Tissue histiocyte - Connective tissue
Microglia - Central nervous system
Peritoneal macrophage - Peritoneal cavity
Red Pulp Macrophage - Spleen
Langerhans cell - Skin and Mucosa
The phagocytotic actions of these cells removes abnormal, old, or dead cells, foreign matter that could be harmful such as from a thorn or splinter and foreign organisms such as viruses and bacteria. Besides phagocytosis, these cells are critical to both innate and adaptive immunity.

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8
Q

Where is the spleen and what is it made from?

A

The spleen is located in the left upper quadrant of the abdomen and consists of red pulp – sinuses lined by endothelial macrophages and cords and white pulp – similar structure to lymphoid follicles

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9
Q

How does blood pass through the spleen?

A

Blood enters the spleen via the splenic artery with white cells and plasma preferentially passing through the white pulp and red cells preferentially passing through the red pulp.

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10
Q

What are the functions of the spleen in adults?

A

The role of the spleen is essentially a blood filter. The red pulp removes old red cells and metabolises the haemoglobin whilst the white pulp synthesises antibodies and removes antibody-coated bacteria and blood cells. The spleen also serves a blood pooling function from which platelets and red cells can be rapidly mobilised during bleeding.
•Extramedullary haemopoiesis – pluripotentialstem cells proliferate during haematological stress or if marrow fails (eg myelofibrosis)
•Immunological function–25% of T cells and 15% of B cells are present in the spleen

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11
Q

What is splenomegaly?

A

Enlarged spleen

Never normal to palpate the spleen below the costal margin.

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12
Q

What could cause splenomegaly?

A

typically associated with an increased workload, for example in haemolytic anaemia where an increased number of defective red cells are removed from the circulation. Other causes include congestion due to portal hypertension (increases back pressure), infiltration by leukaemias and lymphomas and expansion due to accumulation of waste products of metabolism (e.g. in Gaucher’s disease, a defect in the beta-glucosidase enzyme which catalyses the breakdown of glucocerebroside (a constituent of red and white blood cell membranes), causes glucocerebroside to accumulate in fibrils). Some infectious diseases are also characterised by splenomegaly, most notably malaria, schistosomiasis, HIV and glandular fever caused by Epstein Barr virus.

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13
Q

What is there the risk of, if the spleen becomes enlarged and no longer protected by the rib cage?

A

Rupture of the spleen.

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14
Q

What are the possible complications of splenomegaly?

A 
Infarction
Rupture can lead to haematoma 
Anaemia 
Low blood counts can occur due to pooling of blood in the enlarged
spleen = hypersplenism
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15
Q

What is hyposplenism?

A

Hyposplenism is the term used to describe reduced splenic function

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16
Q

What are the causes of hyposplenism?

A

Causes include underlying diseases which destroy spleen tissue such as sickle-cell disease and coeliac disease as well as splenectomy which may be required due to splenic rupture from trauma or because of cancer.

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17
Q

What may a blood film reveal for someone with hyposplenism?

A

A blood film from a patient with hyposplenism will typically reveal Howell-Jolly
bodies which are basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes. During erythropoiesis erythroblasts normally expel their nuclei but in some cases a small portion of DNA remains. Normally such cells would be removed by the spleen so the presence of Howell-Jolly bodies is a good indicator of reduced splenic function.

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18
Q

What are patients at risk from if they have hyposplenism?

A

Patients at risk of overwhelming sepsis, particularly from encapsulated organisms eg Pneumococcus, Haemophilus influenzae and Meningococcus = key clinical fact

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19
Q

What are the functions of red blood cells?

A
  • The function of red blood cells is to transport oxygen from the lungs to all tissues and carry carbon dioxide away.
  • Maintain haemoglobin in its reduced (ferrous) state
  • Maintain osmotic equilibrium
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20
Q

What is the structure of haemoglobin? And how does it aid its function?

A

Haemoglobin is the gas transporting molecule of the red blood cell and this protein takes up ~95% of the cell volume. Adult Haemoglobin A consists of two alpha- and two beta- polypeptide subunits in a α2b2 tetramer. Each subunit is associated with a haem group comprising of a porphyrin ring with ferrous iron (Fe2+) at the centre responsible for binding oxygen. When shifting between the oxygen unbound and oxygen bound states haemoglobin undergoes a conformational change which enhances the binding affinity of subsequent oxygen molecules.This enables haemoglobin to load oxygen in in the lungs where there is a high oxygen tension and release it in the tissues where there is a low oxygen tension and is what gives the oxygen binding curve a sigmoidal shape.

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21
Q

What is the structure of the red blood cell plasma membrane?

A

The erythrocyte cell membrane is a lipid bilayer that contains proteins such as spectrin, Ankyrin, Band 3 and protein. These proteins facilitate vertical interactions with the cytoskeleton of the cell which are essential for maintaining the red cell’s biconcave shape and deformability
The cytoskeleton of an erythrocyte is a lattice structure of long spectrin molecules which are grafted to transmembrane proteins through attachment proteins. This forms a protective “cage” around the erythrocyte.

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22
Q

Describe the synthesis of haemoglobin

A

•Globin gene clusters on chromosome 11 and 16
–Expressed at different stages of life
•Globin chains synthesised independently and combine to form different haemoglobins
•Switch from foetal to adult Haemoglobin occurs at 3-6 months of age
•Foetal and adult Hb and Hb variants have different properties

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23
Q

What is a haemolytic anaemia?

A

Changes in the components of the cell membrane (congenital or acquired) will change the shape of the RBC
This can cause the red cells to be less deformable, more easily broken down and often recognised by the spleen as ‘abnormal’: red cell survival reduces (ie less than 120 days) and anaemia can develop

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24
Q

How does the body respond when a patient becomes anaemic?

A

•Patient becomes anaemic … so reduced pO2 detected in interstitial peritubular cells in kidney
•Increased production of Erythropoietin(hormone) by the kidney
•Erythropoietin stimulates maturation and release of red cells from marrow
•Number of red cells increased and so
Haemoglobin rises
•More oxygen can be delivered
•Via feedback loop, erythropoietin production falls

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25
Q

What condition can an excess of red cell destruction cause?

A

Jaundice

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26
Q

What is cytopenia?

A

• Cytopenia is a reduction in the number of blood cells. It takes a number of forms

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27
Q

What is the name for Low red blood cell count and a high red cell count?

A

Low - Anaemia

High - Polycythaemia or Erythrocytosis

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28
Q

What is the name for a low white cell count and the name for a high white cell count?

A

Low - Leucopenia

High - Leucocytosis

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29
Q

What is the name for a low neutrophil count and what is the name for a high neutrophil count?

A

Low - Neutropenia

High - Neutrophilia

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30
Q

What is the name for a low platelet count and what is the name for a high platelet count?

A

Low - Thrombocytopenia

High - Thrombocytosis or Thrombocythaemia

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31
Q

What is the name for a low all blood cell count and what is the name for a high all blood cell count?

A

Low - Pancytopenia

High - Panmyelosis

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32
Q

What do the descriptions cytosis or philia mean?

A

= An increase in the number of blood cells. It takes a number of forms

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33
Q

What is the name for a low basophil count and what is the name for a high basophil count?

A

Low - Basopenia

High - Basophilia

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34
Q

What is a neutrophil

A

Mature neutrophils migrate to areas of inflammation by chemotaxis where they phagocytose invading microbes and destroy
them by releasing reactive oxygen species. The commonest white cell, essential part of innate immune system. they have a 3-5 lobed nucleus
Once mature, circulate in bloodstream then invade a tissue –live for 1-4 days

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35
Q

How do neutrophils mature?

A 
Controlled by a hormone G-CSF
•↑production of neutrophils
•↓time to release of mature
cells from BM
•enhances chemotaxis
•enhances phagocytosis and killing of pathogens
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36
Q

What would you do if a patient had neutropenia e.g after chemotherapy?

A

Administer recombinant (manufactured) G-CSF

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37
Q

What are the two general causes of neutropenia?

A

Reduced production of neutrophils

Increased removal or use

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38
Q

What would cause increased removal or use of neutrophils enough to cause neutropenia?

A

Immune destruction
Sepsis
Splenic pooling

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39
Q

What would cause a reduction in neutrophil production, enough to cause neutropenia?

A
  • B12/folate deficiency –the building blocks
  • Infiltration of bone marrow by malignancy or fibrosis –no room
  • Aplastic anaemia -empty marrow, no precursors
  • Radiation (if includes high proportion of marrow) –mature cells killed, precursors stunned
  • Drugs –chemotherapy, antibiotics, anti-epileptics, psychotropic drugs, DMARDs, Rituximab –poison the marrow
  • Viral infection –v common-temporarily sick
  • Congenital disorders –not working properly from birth
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40
Q

What are the consequences of neutropenia?

A
  • Severe life threatening bacterial infection
  • Severe life threatening fungal infection
  • Mucosal ulceration eg painful mouth ulcers

Neutropenic sepsis

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41
Q

What must be done if someone has neutropenic sepsis?

A

Immediate intravenous antibiotics

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42
Q

What do monocytes do?

A

Monocytes circulate in the blood for ~1-3 days before moving into tissues where they differentiate into macrophages or dendritic cells. Macrophages protect tissues from foreign substances by phagocytosis, antigen presentation and cytokine production. Monocytes in the blood can also perform phagocytosis after recognising antibodies or complement that coats pathogens or by binding directly via pattern-recognition receptors that recognize pathogens.
• Lysosomes contain lysozyme, complement, interleukins, arachidonic acid, CSF
• Phagocytosis, pinocytosis

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43
Q

What do eosinophils do in the body?

A
  • 3-8 hours in circulation; lifespan 8-12 days
  • Associated with the immune responses to multicellular parasites such as helminths
  • Mediator of allergic response
  • Migrate to epithelial surfaces
  • Granules contain arginine, phospholipid, enzymes
  • Phagocytosis of antigen - antibody complexes
  • Mediate hypersensitivity reactions eg to drugs, in asthma, skin inflammation
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44
Q

What do basophils do in the body?

A
  • Least common but largest
  • active in allergic reactions and inflammatory conditions
  • Dense granules contain histamine, heparin, hyaluronic acid, serotonin
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45
Q

What do lymphocytes do in the body?

A

Originate in the bone marrow

B cells
(Humoral immunity)
- antibody (immunoglobulin) forming cells

T cells
(Cellular immunity)
CD4+ helper cells, CD8+ cells

Natural killer cells
(Cell mediated toxicity)

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46
Q

Why may a healthy person have a value in the full blood count outside of normal?

A

Normal range only includes 95% of healthy population.

  1. 5% normal values above the range
  2. 5% normal values below the range
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47
Q

What things may cause changes in the normal ranges in a full blood count?

A

Age
Sex
Ethnicity
Co-morbidities

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48
Q

What should you do when looking at an abnormal value in a full blood count?

A

Interpret in light of clinical context and previous
FBC (if known)
Think about whether results fit clinical scenario.
If it doesn’t fit or result is unexpected then repeat.

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49
Q

What are the four stages that errors can occur in pathology?

A
  1. Specimen collection
  2. Delivery of specimen to laboratory
  3. Specimen analysis and result reporting
  4. Responsive action
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50
Q

How can errors occur in specimen collection?

A 
Specimen mix up
WBIT
Wrong bottle
Pooling samples
Poor technique
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51
Q

How an errors occur during delivery of specimen to laboratory?

A

Specimen delayed/not delivered

Wrong delivery method

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52
Q

How can mistakes occur during specimen analysis and result reporting?

A 
Specimen mix up (booking in)
Incorrect clinical details
Wrong test requested/performed
Inherent test variability 
Technical error
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53
Q

How can a mistake occur in the responsive action to a test result?

A

Result not reviewed
Reflex tests not carried out
Right result applied to wrong patient

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54
Q

What does a full blood count tell us?

A

Automated test - Required due to high sample throughout
Greater accuracy
Concurrent parameters:
Red cells -Indices, Red cell count, haemoglobin Platelets - Count, size
White cells - Count, full differential

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55
Q

Describe the analyser used for a full blood count

A

The analyser is:
Closed system
Easy to maintain
Able to cope with high numbers of samples

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56
Q

What are the possible techniques used by a full blood count analyser?

A

Spectrophotometry

Flow cytometry

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57
Q

Explain how spectrophotometry works?

A

Amount of light absorbed by sample proportional to amount of absorbent compound within it
Used to measure haemoglobin
Hypotonic solution to lyse cells
Use light of appropriate wavelength
Use calibration curve to determine sample concentration

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58
Q

How does flow cytometry work?

A 
Hydrodynamic focussing  
Single file line of cells 
Pass through light beam
Impedance counting
Forward scatter = size
More scatter = bigger cell
59
Q

What is the flow cytometry differential?

A 
Forward scatter - Size
Side scatter
 - Mono/polymorphonuclear
 -  Intracellular complexity
            - (Granules)
Myeloperoxidase activity
60
Q

For normal blood, how would a test tube if separated out, look like?

A

Cream/yellow plasma at the top made from water, proteins, nutrients, hormones etc.
Then buffy coat made of white blood cells and platelets
Then at the bottom hematocrit made of red cells.
For women 37-47% should be hematocrit
For men 42-52% should be hematocrit

61
Q

How would separated blood look in a test tube for someone with anaemia?

A

Depressed hematocrit percentage

62
Q

How would separated bllood look in a test tube for someone with polycythemia?

A

Elevated hematocrit percentage

63
Q

What is the packed cell volume PCV/Hct (L/L)

A

Proportion of blood that is made up of RBC
Centrifuged blood allows visualisation
Used to assess anaemia but more often polycythemia
Diagnosis and treatment
The PCV/Hct is reduced in polycythemia either by venesection (bleeding) or drug treatment

64
Q

What is haemoglobin concentration?

A

The amount of haemoglobin in blood (g/L). Determined by lysis of red cells followed by conversion of haemoglobin to a stable form and spectrophotometry

65
Q

What may change haemoglobin concentration in the blood?

A

Acute bleed, haemolysis, bone marrow disorders…

Artifactual – dehydration, diuretics…

66
Q

What can cause an overestimation off haemoglobin concentration in the blood?

A

Turbidity of plasma

67
Q

What would cause a reduction in the amount of haemoglobin detected in a sample?

A

In vitro haemolysis/clotted sample

68
Q

What is the red cell count? (RCC)

How is it measured?

A

Number of RBC in given volume of blood
Determined by automated cell counting (interruption of a beam of light or electrical current as a line of single cells flow through a narrow tube). White cells will also be counted but because they are so few in number this does not significantly affect RBC count.

69
Q

What is Mean Cell (or corpuscular) Volume (MCV)?

A

The average volume of red cells measured in femtolitres (10-15 litres) measured automatically by modern analysers (the amount of light or electric current impeded is proportional to the size of the cell). Useful in determining whether an anaemia is microcytic or macrocytic.

70
Q

What types of conditions would result in a high and a low mean cell volume?

A

Insert table

71
Q

What is red cell distribution width (RDW)?

A 
Variation in size of the RBC
If increased = anisocytosis
Used to help assess cause of anaemia
- Increased in iron deficiency (the first parameter to rise as iron stores fall) 
- Usually normal in thalassaemia trait 
- Increased following transfusion
72
Q

What is mean cell haemoglobin (MCH) (pg)?

A

Average amount of haemoglobin protein (measured in pg (10-15 Kg)) in an individual red blood cell. Calculated by dividing haemoglobin concentration in a given volume of blood by the number of red cells in that same volume.

73
Q

What is mean cell haemoglobin concentration (MCHC) (g/L)?

A

Mean concentration of Hb in RBC (Hb/MCV x RCC)
One of least useful parameters:
- usually reduced if hypochromic
- increased if spherocytosis.
- Most useful in laboratory in the identification of cold agglutinins (e.g. viral/ mycoplasma infections etc.)

74
Q

What are reticulocytes?

How are they counted?

A

Reticulocytes are immature red blood cells i.e. the red cells which have just been released from the bone marrow into the blood. Reticulocytes are counted using special stains or fluorescent dyes which bind to ribosomal RNA (rRNA is not present in more mature red cells). The reticulocyte count is a very useful test in evaluating different kinds of anaemia.

75
Q

What conditions would cause and increased and decreased reticulocyte count?

A 
Increased - Haemolytic anaemia
Recent blood loss
Response to iron, Vit B12, folate replacement
Response to EPO
Recovery from bone marrow suppression

Increased - Haematinic deficiency
Bone marrow failure

76
Q

Why would a blood film be required?

A

Sample is ‘flagged’ as requiring a blood film:
• Significant result outside of the normal range
• Significant change within the normal range
• Analyser thinks there are abnormal cells
- Immature cells
- Unable to identify

77
Q

What is a blood film ,and how and why is it done?

A 
• Small drop of blood spread onto glass slide
• 1 cell thick layer 
• Fixed with
methanol 
• Stained to enable
visualisation under
microscope
Blood films are most commonly used to assess causes of low or high counts (RBC/WBC or platelets) and are also used to look for blood parasites (e.g. malaria and filariasis) or to check for abnormalities such as sickle cell anaemia, spherocytosis and thrombotic thrombocytopenic purpura (TTP)
78
Q

What does microcytic mean? (RBC terminology)

A

Small RBCs

79
Q

What does macrocytic mean (RBC terminology)?

A

Large RBCs

80
Q

What does hypochromic mean? (RBC terminology)

A

Pale, less haemoglobin in RBCs

81
Q

What does hyperchromic mean? (RBC terminology)

A

Dense, more haemoglobin in given volume, darker in colour

82
Q

What is Anisocytosis?

A

Greater than normal variation in size of RBCs

83
Q

What is dimorphism?

A

Two distinct populations of RBCs

84
Q

What is Poikilocytosis?

A

Greater than normal variation in red cell shape

85
Q

What are spherocytes?

A

Spherical RBCs (they lack central pallor)

86
Q

What is elliptocytes?

A

Elliptical RBCs

87
Q

What are irregularly contracted cells?

A

Small dense RBC but not as regular in shape as spherocytes

88
Q

What are Acanthocytes?

A

RBCs with small number of irregular spurs. also called spur cells

89
Q

What are sickle cells?

A

Crescent or sickle shaped cells seen in sickle cell disease

90
Q

What are target cells? (RBC terminology)

A

RBC with dark area in the middle of the area of central pallor. Also called codocytes.

91
Q

What are schistocytes?

A

Red cell fragments

92
Q

What is polychromasia? (RBC terminology)

A

Many colours across reticulocytes

93
Q

What are Howell-Jolly bodies?

A

DNA/nuclear fragments in RBCs

94
Q

What is basophilic stippling

A

RNA inclusions in the cytoplasm of RBCs

95
Q

What are pappenheimer bodies?

A

Iron inclusions in RBCs (Perl’s stain)

96
Q

What are Heinz bodies

A

Denatured haemoglobin in RBCs

97
Q

What are haemoglobin H inclusions?

A

‘Golf-ball cells’; Haemoglobin H (Cresyl blue stain)

98
Q 
How might an iron deficiency affect:
- FBC and red blood cell indices
- Reticulocyte count
- reticulocyte haemoglobin content (CHr)
- Blood film
Answer in the form of a table
A

FBC and red blood cell indices - decreased Hb, MCV, MCH, MCHC
increased RDW
May occur in haemoglobinopathies(RCC useful here)
More indicative for iron deficiency than thalassaemia(may be normal)

Reticulocyte count - Low or normal
But…reduced for the degree of anaemia

Reticulocyte Haemoglobin Content (CHr) - Low
Also low in thalassaemia

Blood film - Hypochromic, microcytic, pencil cells, a few target cells
May occur in haemoglobinopathies

99
Q

What blood parameter changes would be seen in spherocytosis?

A 
Haemoglobin (Hb) - N or increase 
Mean Cell Volume (MCV) -  N (reticulocytes also)
RDW - Increase 
MCH - N
MCHC - increase 
Reticulocyte count - increase
100
Q

What would be seen on a blood film of sppmone with a vitamin B12 deficiency

A
  • Oval macrocytes
  • Tear drop poikilocytes
  • Basophilic stippling
  • Howell-Jolly bodies
  • Hypersegmented neutrophil
  • Circulating granulocytic precursors
101
Q

What parameter changes would be see for someone with vitamin B12 deficiency?

A 
Hb - decrease 
RCC - decrease 
RDW - Increase 
MCH - increase
MCHC - no change
MCV* - increase
Hct/PCV - decrease
Reticulocyte count - decrease
102
Q

What are the 5 types of white blood cell?

A 
Neutrophils 
Eosinophils 
Basophils 
Lymphocytes 
Monocytes
103
Q

What can sometimes be counted as a white cell by an analyser and what is done to prevent this?

A

NRBC can be counted as white cells by analyser

Manual differential performed

104
Q

What substance in the blood shows most frequently as a not normal parameter

A

Platelets

105
Q

What may cause low platelet count.

A

 Infection/inflammation
 Iron deficiency
 Drugs….
Clots in the sample

106
Q

When does haemopoiesis begin?

A

In the early embryo this process begins in the vasculature of the yolk sac before shifting to the embryonic liver by ~week 5-8 gestation

107
Q

What are the 5 major lineage pathways for haemopoiesis?

A 
Thrombopoiesis 
Granulopoiesis
Monocytopoiesis 
Lymphopoiesis
Erythropoiesis
108
Q

What is thrombopoiesis?

A

Production of platelets.

109
Q

What are platelets?

A

Platelets have no nuclei and are essentially membrane bound fragments of cytoplasm that bud off from megakaryocytes

110
Q

What are megakaryocytes? And what drives their formation?

A

Megakaryocyte formation is driven by thrombopoietin (TPO). They are very large mononucleate cells with several copies of each pair of chromosomes (i.e. polyploid cells).

111
Q

What is granulopoiesis and how does it work?

A 
Granulopoiesis is the process of making granulocytes. 
The granulocytes (basophils, neutrophils and eosinophils) arise from myeloblast cells which in turn arise from common myeloid progenitor cells.
112
Q

What is monocytopoiesis?

A

Production of monocytes

113
Q

What is Lymphopoiesis?

A

Production of lymphocytes

114
Q

when does development of B lymphocytes begin?

A

The development of B lymphocytes commences in the fetal liver and bone marrow and during their development immunoglobulin genes rearrange to allow production of antibodies with a wide array of specificities

115
Q

How do B lymphocytes mature?

A

Final maturation of B-cells requires exposure to antigen in the lymph nodes and results in mature B- lymphocytes with the capacity to recognize non-self antigens and produce large quantities of specific antibodies.

116
Q

Explain how T lymphocytes are produced and mature to give their function

A

T- lymphocytes progenitors on the other hand arise from fetal liver and migrate to the thymus early in gestation. Immature T cells undergo rearrangement of the T cell receptor genes resulting in the ability to produce a vast array of different T cell receptors which can recognise a wide range of antigens presented to them by antigen-presenting cells.

117
Q

What is Erythropoiesis?

A

Erythropoiesis is the process by which red blood cells (erythrocytes) are produced in the bone marrow.

118
Q

Why does erythropoiesis need to be a constant process?

A

This needs to be a continual process since red blood cells have a finite lifespan of around 120 days in the bloodstream and lack the ability to divide.

119
Q

How do transcription factors and hormones contribute to the process of erythropoiesis?

A

Expression of the transcription factors GATA1, FOG1 and PU.1 commits progenitor cells in the marrow to the erythroid lineage and, once committed, further expansion of the erythroid precursors is largely driven by the hormone erythropoietin released from the kidneys

120
Q

What is erythropoietin?

A

Erythropoietin is a 165 amino acid glycoprotein hormone and its main function is to inhibit apoptosis (programmed cell death) of CFU-E (colony-forming units of the erythroid cell line) progenitor cells

121
Q

How are reticulocytes formed? And then how do they become RBCs?

A

Activation of the erythropoietin receptor on these cells allows them to develop, proliferate and differentiate. During this process nucleated erythroblasts extrude their nucleus and most of their organelles ultimately forming reticulocytes (immature red blood cells) which are then released into the circulation. Once in the bloodstream reticulocytes extrude their remnants of organelles such as mitochondria and ribosomes and take ~1 to 2 days to mature into red blood cells

122
Q

Why are red blood cells particularly susceptible to oxidative damage? Give examples

A

Since mature red blood cells lack nuclei, they are unable to replace damaged proteins by re-synthesis making them particularly susceptible to oxidative damage in diseases such as glucose-6-phosphate dehydrogenase deficiency Similarly, a lack of mitochondria and therefore a reliance on glycolysis for energy production makes the biochemical consequences of the disease pyruvate kinase deficiency particularly relevant to red blood cells.

123
Q

Erythrocytes make up roughly what proportion of the total blood volume?

A

40-50%

124
Q

What is the shape of an erythrocyte and how does this aid its function?

A

They are anucleate biconcave discs ~ 8 μm in diameter with a flattened depressed centre which gives them a dumbbell-shaped cross section. This distinctive shape optimises the laminar flow properties of blood in large vessels as well as allowing the cells to deform to squeeze through the smallest capillaries (~3.5 μm in diameter).

125
Q

What reduces the affinity of haemoglobin to oxygen

A

The affinity of haemoglobin for oxygen is decreased by 2,3-Bisphosphoglycerate (BPG) (an intermediate of glycolysis), a fall in pH or an increase in CO2 (the Bohr effect), all producing a rightward shift in the oxygen dissociation curve. Conversely, a fall in CO2, a fall in BPG or an increase in pH would result in a leftward shift in the dissociation curve due to increased affinity of haemoglobin for oxygen.

126
Q

How does adult haemoglobin transfer oxygen to foetal haemoglobin?

A

The composition of the globin subunits of haemoglobin determined by expression of different globin genes also influences oxygen affinity. For example, fetal haemoglobin has a higher binding affinity for O2 than adult haemoglobin which allows transfer of O2 to foetal blood from the mother.

127
Q

What happens to haemoglobin after RBCs are broken down in the spleen by the reticuloendothelial system?

A

The spleen has a particularly prominent role in the reticuloendothelial system in filtering blood to remove deformed and old cells from the circulation. The haemoglobin removed from senescent erythrocytes is recycled by the spleen with the globin portion being degraded to its constitutive amino acids and the haem portion metabolised to bilirubin, which is subsequently removed in the liver where it is conjugated and secreted in bile. Bacteria in the colon deconjugate and metabolise the bilirubin into colourless urobilinogen which is subsequently oxidized to form urobilin and stercobilin (these are responsible for the brown colour of stool). A small amount of the urobilinogen is reabsorbed and processed by the kidneys which gives, urine its yellow colour.

128
Q

Can one survive without a spleen?

A

Patients can usually survive without a spleen, as sometimes happens in the case of surgical removal after accidental rupture due to trauma or to treat diseases such as hereditary spherocytosis. In such cases there is an increased risk of sepsis and patients are usually given various vaccinations to compensate for inadequate opsonisation of bacteria

129
Q

What is a full blood count? (FBC)

A

A “full blood count” (FBC) is the term used to refer to a panel of tests routinely performed on a blood sample in order to determine whether or not any haematological abnormalities are present. Such tests are normally performed in the lab on automated analysers capable of processing many hundreds of samples in a day.

130
Q

What must a blood sample for a FBC contain and why?

A

Blood samples for FBC must always be placed in a tube containing EDTA (ethylenediaminetetraacetic acid) and mixed. EDTA chelates Ca2+ ions and therefore acts as an anticoagulant. Without a chelating agent the blood sample would clot and be useless for analysis. NOTE: If you are also taking a blood sample for UE analysis (urea and electrolytes) never pour blood from the FBC tube into the UE tube as the K+ salt of EDTA is often used in the FBC tube and this would give a spuriously high K+ reading (some clinicians are tempted to do this if the patient was difficult to bleed!)

131
Q

How would RBC count be affected by a microcytic anaemia?

A

Microcytic anaemia, red cell count is:

  • Reduced in iron deficiency anaemia
  • Increased in thalassemia trait
132
Q

How can Red blood cell count be used to look at erythrocytosis?

A

Erythrocytosis: if red cell count elevated, more likely to be a true polycythaemia
- spurious (false) polycythaemia caused by decreased plasma volume, RCC won’t be increased

133
Q

What is white cell count? (WBC)

How is it calculated?

A

Number of white blood cells in a given volume.
White blood cells count (WBC)
Determined by automated cell counting (interruption of a beam of light or electrical current as a line of single cells flow through a narrow tube) after the red blood cells have been lysed in the sample.

134
Q

What is the name for a low lymphocyte count and what is the name for a high lymphocyte count?

A

Low - Lymphocytopaenia

High - Lymphocytosis

135
Q

What is the name for a low monocyte count and what is the name for a high monocyte count?

A

Low - Monocytopaenia

High - Monocytosis

136
Q

What is the name for a low eosinophil count and what is the name for a high eosinophil count?

A

Low - Eosinopenia

High - Eosinophilia

137
Q

What is Haematocrit (HCT)?

How has the calculation changed?

A

This is the fraction of whole blood volume that consists of red blood cells. Previously this was measured by centrifuging the blood sample and comparing the height of the red cell fraction with the height of the total blood (this would give the Packed cell volume (PCV)). Nowadays, to be compatible with the high throughput required in analysis labs the PCV measurement is replaced by the calculation of multiplying the average red cell size (the mean cell volume (MCV)) by the number of red cells per litre to give the Haematocrit.

138
Q

what are normochromic or normoncytic cells?

A

No abnormal staining characteristic. Normal sized RBCs

139
Q

What is microcytosis?

A

Presence of abnormally small RBCs

140
Q

What is macrocytosis?

A

Presence of abnormally large RBCs

141
Q

What are ovalocytes?

A

RBCs oval in shape

142
Q

What are stomatocytes?

A

RBC with slit like stoma

143
Q

What are echinocytes?

A

RBC with large number of regular spurs. Also called crenated cells

144
Q

What is Aggulination

A

RBCs forming irregular clumps

MEH (11 decks)

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