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S3 Flashcards

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1
Q

What is hemopoiesis?

A

the production of blood cells (red blood cells, platelets and most white blood cells) occurring in the bone marrow

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2
Q

Where does hemopoiesis occur in infants and adults?

A

In infants, it takes place throughout the skeleton

In adults: pelvis, sternum, skull, ribs and vertebrae.

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3
Q

What is a trephine biopsy?

A

bone marrow biopsy

Can look at architecture of the bone marrow

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4
Q

What are the five major lineage pathways that arise from haemopoietic stem cells?

A 
Thromopoeisis
Granulopoiesis
Monocytopoiesis
Lymphopoeisis
Erythropoiesis
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5
Q

What is haemopoietic stem cell differentiation determined by?

A

Hormones
Transcription factors
Interactions with non-haemopoietic cell types e.g. endothelial cells

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6
Q

What are two important hormone that control haematopoiesis?

A

Erythropoietin secreted by kidney stimulates RBC production

Thrombopoietin produced by liver and kidney regulates production of platelets

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7
Q

Describe the properties of haemopoietic stem cells

A

Self renewal
Can differentiate given appropriate stimuli= common myeloid progenitor cells or common lymphoid progenitor cells
Extramedullary haematopoiesis- can be physiologic or pathologic

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8
Q

Name sources of HPSC

A

Bone marrow aspiration
GCSF mobilised peripheral blood stem cells collected by leucopharesis
Umbilical cord stem cells

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9
Q

What is the reticuloendothelial system?

A

Part of the immune system

Made up of monocytes in blood and network of tissues that contain phagocytic cells

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10
Q

Describe the types of macrophages and the tissue where it is found

A 
Kuffer cell- liver
Tissue histocyte- connective tissue
Microglia- CNS
Peritoneal macrophage- peritoneal cavity
Red pulp macrophage- spleen
Langerhans cell- skin and mucosa
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11
Q

Describe the red pulp of the spleen

A

Sinuses lined by endothelial macrophages and cords

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12
Q

Describe the white pulp of the spleen

A

Similar structure to lymphoid follicles

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13
Q

What are the functions of the spleen?

A

Sequestration and phagocytosis-old/abnormal RBC removed by macrophages
Blood pooling= platelets and RBC can be rapidly mobilised during bleeding
Extramedullary hameopoiesis= pluripotential stem cells proliferate during haematological stress or if marrow fails
Immunological function = 25% of T cells and 15% of B cells are present in spleen

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14
Q

What would cause splenomegaly?

A

an increased workload (e.g. overworking red or white pulp)
Back pressure due to portal hypertension.
Infiltrated by foreign cells – cancer cells of blood origin (e.g. leukaemia) and other cancer metastases; infectious diseases (e.g. malaria, schistosomiasis and HIV).
Accumulation of waste products of metabolism.
Extramedullary haemopoiesis
Expanding as infiltrated by other material e.g. sarcoidosis

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15
Q

How do you examine the spleen?

A

You will be able to palpate an enlarged spleen below the costal margin, when palpating up from the right iliac fossa (which is abnormal).
Can feel spleen edge moving towards your hand on inspiration
As it is no longer protected by the ribs, the risk of rupture is increased=haematoma.

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16
Q

What is hypersplenism?

A

a common disorder characterised by an enlarged spleen which causes rapid and premature destruction of blood cells

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17
Q

Name mild clinical cases of splenomegaly

A

Infectious hepatitis
Endocarditis
Infiltrative disorders e.g. sarcoidosis
Autoimmune diseases

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18
Q

Name moderate clinical cases of splenomegaly

A 
Lymphoma
Leukaemias
Myeloproliferative disorder
Liver cirrhosis with portal hyper tension
Infections e.g. glandular fever
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19
Q

Name massive clinical cases of splenomegaly

A

Chronic myeloid leukaemia
Myelofibrosis
Malaria
Schistosomiasis

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20
Q

What is hyposplenism?

A

Reduction in the Function of the Spleen

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21
Q

Name causes of hyposplenism

A

Splenectomy (surgical removal of the spleen) - this may be required due to splenic rupture from trauma; cancer or to treat diseases such a hereditary spherocytosis.
Diseases that destroy splenic tissue (e.g. sickle cell disease and coeliac disease).
Autoimmune disorders- systemic lupus, RA

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22
Q

What are Howell-Jolly bodies?

A

red blood cells with remnants of DNA still in the cytoplasm). These are indicative of damage as a functioning spleen would remove these as they passed through

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23
Q

What are patients with hyposplenism at risk of?

A

increased risk of developing sepsis, especially from encapsulated organisms (Neisseria meningitidis, Streptococcus pneumoniae & Haemophilus influenzae).
=White pulp can no longer remove the bacteria and therefore they remain in the body, allowing them to cause further infection.

Patients are usually given various vaccinations to compensate for this.

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24
Q

On which chromosomes are globin gene clusters found?

A

Chromosome 11 and chromosome 16

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25
At what age does feral Hb switch to adults Hb?
~3-6 months of age
26
What is haemolytic anaemia?
Changes to plasma membrane cause cells to become less deformable and more fragile Spleen recognises cells as ‘abnormal’ and removes them from circulation This can cause haemolytic anaemia where red blood cells are destroyed faster than they can be made
27
What proteins are involved in hereditary spehrocytosis?
Band 3 – A Cl-/HCO3- exchanger (integral protein) which links to protein 4.2 and ankyrin. Ankyrin – Links integral membrane proteins to the underlying spectrin-actin cytoskeleton. Protein 4.2 – ATP-binding protein which may regulate the association of band 3 with ankyrin. Spectrin – Crosslinks with actin, forming a molecular scaffold that links the plasma membrane to the actin cytoskeleton.
28
Describe the process of haem degradation
Senescent red blood cells engulfed by macrophages in reticuloendothelial system Heam= iron recycled Unconjugated bilirubin transported in blood bound to albumin Bilirubin taken up by liver and conjugated with glucuronic acid=bilirubin diglucuronide Secreted in bile into duodenum Glucuronic acid removed by bacteria= bilirubin converted into urobilinogen which is subsequently oxidised to sterocobilin (makes faeces brown) Some urobilinogen absorbed into blood and transported to kidney=oxidised to urobilin and excreted in urine
29
How does G-CSF stimulate neutrophil maturation?
Increases production of neutrophils Speeds up release of mature cells from BM Enhances chemotaxis Enhances phagocytosis and killing of pathogens
30
Name the causes of neutrophilia
Infection Myeloproliferative diseases Cytokines (G-CSF) ``` Tissue damage Smoking Drugs Acute inflammation Cancer Metabolic disorders Endocrine disorders Acute haemorrhage ```
31
Why does acute haemorrhage cause neutrophilia?
Cells in circulating pool are measured in a blood count | Haemorrhage brings more cells out from marginated pool
32
What are the consequences of neutropenia?
Severe life-threatening bacterial infection Severe life-threatening fungal infection Mucosal ulceration
33
What are the reduced production causes of neutropenia?
``` B12/folate deficiency Aplastic anemia Viral infection Congenital Drugs Radiation Infiltration- no room for blood cell production ```
34
What are the increased removal or use causes of neutropenia?
Immune destruction Sepsis Splenic pool
35
What are the causes of monocytosis?
Bacterial infection e.g. TB Inflammatory conditions e.g. RA Carcinoma Myeloproliferative disorders and leukaemias
36
What are the common causes of eosinophilia?
``` Allergic diseases Parasitic infection Drug hypersensitivity Skin diseases Churg-strauss- very rare autoimmune condition= inflammation of small blood vessels ```
37
What are the rare causes of eosinophilia?
``` Hodgkin lymphoma Acute lymphoblastic leukaemia Acute myeloid leukaemia Myeloproliferative conditions Eosinophilic leukaemia Idiopathic hypereosinophilic syndrome ```
38
What causes reactive basophilia?
Immediate hypersensitivity reactions Ulcerative colitis RA
39
What causes myeloproliferative basophilia?
Chronic myelogenous leukemia Myeloproliferative neoplasms Systemic mastocytosis
40
What causes reactive lymphocytosis?
``` Viral infections Bacterial infections Stress related: MI/cardiac arrest Post splenectomy smoking ```
41
What cause is lymphoproliferative lymphocytosis?
Chronic lymphocytic leukaemia (B cells) T or NK cell leukaemia Lymphoma (cells spill out of infiltrated bone marrow)
42
What does the normal range include?
Only includes the middle 95% of the healthy population, meaning there is 2.5% of the population out of the normal on either side whose results are normal for themselves.
43
Name factors that changes the normal range of Hb
Most common: Age, Sex Ethnicity Co-morbidities
44
How do you interpret haematology results?
Considering clinical context and previous FBC if known
45
Describe the flow of errors in pathology results?
Specimens collections Delivery of specimen to laboratory Specimen analysis and result reporting Responsive action
46
Where can errors occur in specimen collection?
The specimen could be mixed up. There could be the wrong blood in the tube (blood is not that of the patient identified on the label). The wrong bottle could be used (different bottles are required for different samples as they contain specific agents for that test). There could be pooling of different samples (repeated venepuncture to get a full tube). Poor technique can trigger the clotting cascade in the blood and alter the values so they cannot be used correctly.
47
Where can errors occur in the delivery of specimen to laboratory?
The specimen can be delayed or not delivered. A FBC must be processed within two hours of sampling, otherwise it is unusable. The specimen can be delivered by the wrong method. Some samples need to be delivered at body temperature while others need to be hand delivered as the air tube system used in some hospitals distorts the analyte which you are looking at.
48
Where can errors occur in specimen analysis and result reporting?
Specimen mix up can occur due to human error, or the huge number of samples sent to the labs. Incorrect clinical details can be due to poor handwriting being misread, or the wrong thing is written down. The wrong test requested or performed. There is inherent test variability for the analysers as they are not 100% accurate all the time. Technical errors can occur with the analysers.
49
Where can errors occur in responsive action?
``` Sometimes nothing is done in response to an abnormal result. Reflex tests (extra tests required in response to the results of the FBC) are not carried out. The right result is applied to the wrong patient. ```
50
How is full blood count analysed and what are the essential parameters?
Automated test- greater accuracy
51
What are the FBC analyser techniques?
Spectrophotometry Flow cytometry Flow cytometry differential
52
What is spectrophotometry?
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 to calibration curve to determine sample concentration
53
What is flow cytometry?
Hydrodynamic focussing- single file line of cells passes through light beam Impedance counting Forward scatter=size More scatter=bigger the cell
54
What is flow cytometry differential?
Forward scatter=size Side scatter=mono/polymorphonuclear, IC complexity (granules) Myeloperoxidase activity
55
What is packed cell volume (PVC) and what is it used to assess?
Proportion of blood that is made up of RBC | Used to assess anaemia but more often polycythemia = PCV reduced
56
What can cause an abnormal Hb results?
Turbidity of plasma can give an overestimate
57
What is red cell count and what is it used to assess?
Number of RBC in given volume of blood | Used to assess anaemia and erythrocytosis
58
What is mean cell volume?
Mean RBC size measured using the amount of light scattered as they pass in a single file past a laser
59
What is the most important parameter used to screen the cause of anaemia?
Mean cell volume
60
What causes a high MCV?
``` Megaloblastic anaemia (b12, folate deficiency) Liver disease Alcohol, smoking Haemolytic anaemia Bleeding Hypothyroidism Myeloma Myelodysplasia ```
61
What causes low MCV?
Iron deficiency anaemia Thalassaemia Anaemia of chronic disease Lead poisoning
62
What is mean cell haemoglobin?
Average measure of the amount of Hb in each RBC | Used to assess anaemia- low in iron deficiency, normal or increased in macrocytic anaemias
63
What is red cell distribution width and what is it used to assess?
Variation in size of RBC Increased = anisocytosis Used to help assess cause of anaemia =increased in iron deficiency, normal in thalassaemia trait, increased following transfusion
64
What is reticulocyte count?
Measurement of the number of young erythrocytes | Identified using size and RNA content
65
What does increased reticulocyte count indicate?
``` Haemolytic anaemia Recent blood loss Response to iron, VitB12, folate replacement Response to EPO Recovery from bone marrow suppression ```
66
What does reduced reticulocyte count indicate?
Haematinic deficiency | Bone marrow failure
67
When is a sample flagged for a blood film?
Samples with significant results outside of the normal range, significant change within the normal and abnormal (either immature or unable to identify) cells highlighted by the analyser are identified
68
How do you create a blood film?
Place a drop of the patient’s blood onto a glass slide and spread it until it is a layer only one cell thick. This allows the cells to be viewed much more clearly as they are not being distorted by cells on-top of or below the red blood cells which we’re trying to observe. Fix the film with methanol to prepare the cells for staining and to protect the observer from any infectious diseases in the blood. Stain the film with methylene blue and eosin dyes to enable clear visualisation under the microscope.

MEH (3 decks)

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