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MEH My own decs > Session 6: Haemopoeisis, Spleen and Bone Marrow > Flashcards

Session 6: Haemopoeisis, Spleen and Bone Marrow Flashcards

1
Q

What is haemopoesis?

A
  • It is the process by which blood cells are formed.
  • It involves specification of blood cell lineages and proliferation, to maintain an adequate number of cells in the circulation.
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2
Q

Compare haemopoiesis in adult vs children and infants

A

Infants and children: extensive throughout skeleton

Adult:

Limited in adult to 5 areas:
Pelvis, Sternum, Skull, Ribs and Vertebrae

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3
Q

How to sample bone marrow?

A

Trephine biopsy

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4
Q

5 major pathways for haemopoetic stem cells

A

Common lymphoid –>

lymphocyte (lymphopoesis)

Common myeloid progenitor –>

platelets (thrombopoesis)
Erythrocytes (erythropoesis)
Monocyte/macrophage (monocytopoesis)
Basophil, Neutrophil, Eosinophil (granulopoesis)

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5
Q

What is differentiation into different blood cell linages determined by?

A

Hormones
Transcription factors
Interactions with other non-haemopoetic cell types, like endothelial cells

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6
Q

Name the hormones involved in haemopoesis.

Where are they produced and what do they do?

A

Erythropoetin (from kidney, stimulates RBC production)

Thrombopoetin (from kidneys and liver, regulates platelet production)

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7
Q

Haemopoetic stem cells (3)

A

Capable of self renewal (more than any other adult tissue)

Can differentiate into variety of specialised cells, given appropriate stimuli

In Pathological conditions, (myelofibrosis/thalasaemia) they can mobilize into circulating blood to colonise other tissues. (like the spleen and liver). This is called extramedullary hamatopoeiesis

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8
Q

What is it called when blood cells are produced in other tissues?

A

Extramedullary haemopoesis

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9
Q

Sources of haemopoetic stem cells (for transplant)

A

Bone marrow aspiration (rare)

Umbillical cord blood stem cells (cord bank)

Granulocyte colony stimulating factor (GCSF) mobilises peripheral blood stem cells and they are collected via leucopharesis

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10
Q

What is the RES (reticuloendothelial system)

A
  • Part of the Immune system made up of monocytes in blood and a network of tissues which contain phagocytic cells
  • Main organs are liver and spleen
  • Spleen RES cells dispose of RBC (if damaged/old)
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11
Q

Different macrophages and location

A

Kupffer cell (liver)
Tissue histiocyte (connective tissue)
Microglia (CNS)
Peritoneal macrophage (peritoneal cavity)
Red pulp macrophage (spleen)
Langherhans cell (skin and mucosa)

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12
Q

Spleen pulps

A

Red pulp: sinuses lined by endothelial macrophages

White pulp: similar structure to lymphoid follicles

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13
Q

Function of spleen

A

Sequestration and phagocytosis (old/abnormal RBC removed by macrophages)

Blood pooling (allows a rapid supply of red blood cells and platelets during bleeding)

Extramedullary haemopoesis (if marrow fails or under stress, e.g. in myelofibrosis)

Immunological function (25% of T cells and 15% of B cells are present in the spleen)

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14
Q

How does blood enter spleen?

A

Via splenic artery

  • White cells and plasma pass through white pulp
  • Red cells through red pulp

(preferentially)

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15
Q

Why does splenomegaly occur?

A
  • Portal hypertension (liver disease)

(patients which have liver disease, its very difficult for blood to flow round liver. There is a connection in the portal system between liver and spleen, so the blood can’t come out of the spleen as easily, so spleen becomes engorged with blood as there is this back pressure due to portal hypertension)

  • Over work (red/white pulp)
    (e. g. patients with sickle cell disease)
  • Extramedullary haemopoesis causes spleen to be full of developing blood cells
  • Infiltrated by cells (like cancer cells or other cancer metastases)
  • Iinfiltrated by other material such as in sarcoidosis, granulomas are present in the spleen, which enlarges it
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16
Q

How to examine spleen?

A
  • It is never normal for the spleen to be palpable below the costal margin
  • Start to palpate in Right Iliac Fossa (RIF) and move up or may miss massive splenomegaly
  • Put your hand in, ask the patient to brethe in and feel for spleen edge moving towards your hand
  • Feel for the splenic notch
  • Record how big it is by measuring in cm from costal margin in mid- clavicular line
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17
Q

Massive splenomegaly causes

A

Chronic myeloid leukaemia
Myelofibrosis
Malaria
Schistosomiasis

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18
Q

Moderate splenomegaly

A
  • Lymphoma
  • Leukaemias
  • Myeloproliferative disorders
  • Liver cirrhosis with portal hypertension
  • Infections (eg Glandular fever)

Could also be due to all the causes of massive splenomegaly, but just in an earlier stage)

  • Chronic myeloid leukaemia
  • Myelofibrosis
  • Malaria
  • Schistosomiasis
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19
Q

Mild splenomegaly

A
  • Infectious hepatitis
  • Endocarditis
  • Sarcoidosis/infiltrative disorders
  • Autoimmune diseases

Could also be due to all the causes of massive and moderate splenomegaly, but just in an earlier stage)

  • Chronic myeloid leukaemia
  • Myelofibrosis
  • Malaria
  • Schistosomiasis
  • Lymphoma
  • Leukaemias
  • Myeloproliferative disorders
  • Liver cirrhosis with portal hypertension
  • Infections (eg Glandular fever)
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20
Q

What can occur in blood counts for hypersplenism?

A

Low blood counts due to pooling of blood in enlarged spleen

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21
Q

Risk with splenomegaly

A

Risk of rupture (no longer protected by rib cage)
Avoid contact sports and rigourous activity

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22
Q

What is hyposplenism?

A

Lack of functioning splenic tissue

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23
Q

Causes of hyposplenism

A

Splenectomy (may be required due to splenic rupture from trauma or beasue of cancer)

Sickle cell disease (in older children and adults due to multiple infarcts/fibrosis)

GI disease (coeliac, crohns, ulcerative collitis)

Autoimmune disorders (systemic lupus, Rheumatoid Arthritis , Hashimoto’s disease)

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24
Q

Blood sign of hyposplenism

A

Howell Jolly bodies (contain DNA remnants, would usually be removed by functioning spleen)

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25
What are patients with hyposplenism at risk of?
At risk of sepsis from encapsulated bacteria: - Streptococcus pneumoniae - Meningococcus - Haemophilus influenzae
26
Prevention for encapsulated bacteria infection (for patients with hyposplenism)
Patients must be: - Immunised - Given life-long antibiotics prophylaxis
27
What does MCV show?
Mean size of RBC
28
RBC structure
No nucleus No mitochondria 120 day lifespan Biconcave, flexible disc
29
Function RBC
- Deliver O2 to tissues - Carry haemoglobin - Maintain haemoglobin in reduced (ferrous) state - Maintain Osmotic equilibrium - Generate energy
30
What happens at 3-6 months of age?
Switch from fetal to adult Hb at 3-6 months old
31
Haemoglobin structure
Two alpha sub units and two beta sub units Each globin molecule has a haem, which contains an iron
32
What can occur if changes occur in RBC plasma membrane?
Haemolytic anaemia: - Cells become less deformable and more fragile - Spleen recognises them as abnormal and removes them from circulation - Resulting in haemolytic anaemia
33
Disease relating to changes in RBC membrane
Hereditary spherocytosis
34
RBC membrane proteins
Spectrin (molecular scaffold that links plasma membrane to actin cytoskeleton) Ankyrin (links integral proteins to spectrin-actin cytoskeleton) Band 3 (chloride and bicarbonate exchange) Protein 4.2 (ATP binding protein)
35
How is haem degraded?
1) Red cells are identified as abnormal by macrophages 2) The macrophages in the RES system engulf the RBC's and break them down 3) The Fe2+ is released and recirculated (recycled) 4) The haem portion is metabolised to bilirubin (unconjugated)
36
What happens to (unconjugated) billirubin?
* It is transported to the liver (bound to albumin in the blood) * The liver conjugates the bilirubin with glucuronic acid to form bilrubin diglucoronide
37
What happens to bilirubin diglucoronide?
Secreted in bile into duodenum Converted to urobillogen ``` Urobillogen can be oxidised to: stercobilin (in faeces = brown) or urobilin (in urine = yellow) ```
38
What means increase in cells
Cytosis / philia
39
What means decrease in cells
penia
40
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41
Describe the role of neutrophils
* First responder phagocyte * Essential part of Innate immune system * Circulate blood stream and phagocytose invading microbes and destroy them by by releasing reactive oxygen species.
42
What do Neutrophils look like on a blood film
3-5 segments of nucleus
43
What is maturation of neutrophils controlled by?
G-CSF (which is a glycoprotein, growth factor and cytokine)
44
What does G-CSF do?
* Increases production of neutrophils * Speeds up release of mature cells from BM * Enhances chemotaxis * Enhances phagocytosis and killing of pathogens
45
G-CSF clinical relevance
Recombinant G-CSF is routinely administered when more neutrophils are needed eg patient with sever neutropenia and sepsis after chemotherapy
46
What is Neutrophilia?
Increase in the absolute number of CIRCULATING neutrophils (some are marginated against vessel wall)
47
Causes of neutrophilia
- Infection or inflammation (most common cause) e.g. - Tissue damage - Drugs (ie steroids) - Smoking - Acute inflammation - Cancer - Myleoproliferative diseases (rare) - Cytokines (eg G-CSF) - Acute Haemorrhage (brings marginated pool cells out) - Metabolic disorders - Endocrine disorders
48
Causes of neutropenia types
Reduced production or increased removal or use
49
Reduced production neutropenia causes
B12/folate deficiency Infiltration (maligancy/fibrosis) Aplastic anaemia (empty marrow) Viral infection Congenital Radiation (mature cells killed, precursors stunned) Drugs (chemo) Be Careful Doing Any IV Radiation Arthur(nmeumonic)
50
Increased removal/use causes of neutropenia
``` Immune destruction (autoantibodies) Sepsis (they rush to tissues and marrow cannot compensate) Splenic pooling (sequestration) ``` sis (NMEUMONIC)
51
Consequences of neutropenia
Severe life threatening bacterial infection Severe life threatening fungal infection Mucosal ulceration e.g. painful mouth ulcers
52
Neutropenia emergency
Neutropenic sepsis = medical emergency Intravenous antibiotics immediately
53
Describe the role of Monocytes (4)
- Largest cells in blood - Monocytes circulate in the blood for 1-3 days before moving into tissues where they differentiate into macrophages or dendritic cells. - Phagocytose microorganisms and breakdown/remove cellular debris - Antigen presenting role to lymphocytes - Important in defence against chronic bacterial infections (e.g. tuberculosis and chronic fungal infections)
54
What do macrophages protect against?
Bacterial infections (TB and chronic fungal infections)
55
Causes of monocytosis
* Bacterial infection (e.g. TB) * Inflammatory conditions (Rheumatoid arthiritis, Crohns, ulcerative colitis) * Carcinoma * Myeloproliferative disorders and Leukaemias My car is blue (nmeuonic)
56
Monocyte appearance
purple with large nucleus
57
Eosinophils purpose (6)
* Responsible for immune response against multicellular parasites such as helminths - think of EO candy won (helminths are basically like worms in your blood) * Mediator of allergic responses * Phagocytosis of antigen-antibody complexes * Granules release cytotoxic proteins * Lifespan 8-12 days * Circulate for 3-8 hours before moving into tissues
58
What do eosinophils release?
Their granules contain an array of cytotoxic proteins e.g. eosinophil cationic protein and elastase
59
Eosinophil appearance
Tomato with sunglasses (very pink, 2 lobed nucleus)
60
Inappropriate activation of eosinophils can result in…
Tissue damage and inflammation - e.g. in asthma
61
Common causes of eosinophilia
Drug hypersensetivity (penicillin) Allergic diseases (asthma, eczema, hay fever) Parasitic infections (tapeworm, helminths, round worm) Skin disease (bullous pemphigoid) Churg-Strauss (very rare autoimmune condition resulting in inflammation of small blood vessels) Don't all people sea colour - sunglasses blood cell - cant see colours
62
Rare causes of eosinophilia
Hodgkin Lymphoma Acute Lymphoblastic leukaemia Acute myeloid leukaemia Myeloproliferative Idiopathic hypereosinophilic syndrome Has Anyone Ever Melted An Icecream
63
Basophils appearance
Blackberry - purple blobs (granules mask nucleus because stain deep blue)
64
What do basophil granules contain?
Histamine Heparin Hyaluronic acid Serotonin
65
Basophil function
Activated in allergic reactions and inflammatory conditions - Do not eat the poisonous berries in fishermen as you can have an allergic reaction Contain histamine, heparin, serotonin, which they release as part of the immune response Basophils are the least common wbc
66
What are the reactive disorders that cause basophilia?
Hypersensitivity reactions Ulcerative collitis Rheumatoid Arthiritis
67
What are the Myeloproliferative disorders that cause basophilia?
Chronic myeloid leukaemia Systemic mastocytosis
68
Lymphocytes appearance
deeply stained nucleus (purple) and small amount of cytoplasm) - D in the photo
69
Types of lymphocytes and their roles
B cells: * humoral immunity - Bekah is funny * Antibody production * Presenting antigens to T cells to activate the T cells T cells: * cellular immunity * direct killing of infected host cells * Activate and stimulate other immune cells to partake in the immune response * Include CD8+ helper cells and CD4+ cells Natural killer cells: * (cell mediated cytotoxicity) - direct action in killing abnormal cells or pathogens within the blood
70
Reactive disorders that cause lymphocytosis
Viral infections Bacterial infections - especially whooping cough Stress related: MI /cardiac arrest Post splenectomy Smoking
71
Lymphoproliferative (malignant) disorders that cause lymphocytosis
Chronic lymphocytic leukaemia T or NK cell leukaemia Lymphoma (cells spill out of infiltrated bone marrow)
72
What happens in people with haemolytic anaemias?
They can appear jaundiced: * Because there is too much breakdown of erythrocytes, so excess unconjugated bilirubin in the blood * Liver might not be able to deal with the bilirubin quickly enough so can cause jaundice (ie yellow sclera)
73
Name cell A-E
A - Neutrophil (3-5 segments of nucleus) B - Monocyte C - Basophil (looks like a blackberry and dark stained granules) D - Lymphocyte (deeply stained nucleus and small amount of cytoplasm) E - Eosinophil

MEH My own decs (13 decks)

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