Haemapoesis Flashcards

1
Q

What is haempoiesis?

A

It is the production of blood cells and it occurs in the bone marrow.

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2
Q

How it Bone marrow distributed?

A

In infants bone marrow is widely distributed but in adulthood, bone marrow is in the Pelvis, Sternum, Skull, Ribs, Vertebrae

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3
Q

How is haemopoiesis controlled?

A

It is controlled by hormones.

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4
Q

What types of blood cell are there?

A
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5
Q

What are some characteristics of haemopoietic stem cells?

A
  • It 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 depending on the different stimuli.
  • It can mobilise out of the bone marrow into circulating blood
  • It can undergo apoptosis.
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6
Q

What are the sources of HPSC?

A

Used to used aspiration of bone marrow (be put under anaesthetic and suck 2L out of bone marrow using a needle). Rarely done anymore.

Now, GCSF mobilised stem cells in the peripheral blood (collected by leucopharesis) - This is when you stimulate stem cells to go into the blood and collect the stem cells by using an aphoresis machine. This method is what happens if donating stem cells to a siblign or as a voluntary donor.

Umbilical cord stem cells. These are donated by people wo have just had a baby and are usually used for children.

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7
Q

What is therReticuloendothelial system?

A

The RES is a network in blood and tissues which is part of the immune system containing phagocytic cells:

  • Monocytes
  • Macrophages
  • Kuffper cells
  • Tissue Histiocytes
  • Microglial cells in the CNS.

Cells of the RES can identify and mount an appropriate immune response to foreign antigens.

The main organs are the liver and the spleen.

All blood passes through thr speen, the RE cells in the spleen can dispose of blood cells, in particular damaged or old red cells.

Extracellular fluid travels via lymphatics to the lymph nodes.

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8
Q

What does the spleen consist of?

A

Red pulp - sinuses lined by endothelial macrophages and cords

White pulp - similar to the structure of lymphoid follicles

White cells and plasma preferentially pass through white pulm whereas red cells preferentially pass throguh red pulp.

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9
Q

Blood supply of spleen?

A
  • The spleen gets its bloos via the splenic artery that splits into multiple arterioles.
  • Blood then leaves through venules joining splenic vein, into superior mesinteric vein then into the portal vein.
  • Remember: The portal vein takes blood from splenic vein.
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10
Q

What are the functions of spleen in adults?

A

Sequestration and phagocytosis - old / abnormal red cells removed by macrophages.

Blood pooling - platelets and red cells can be repaidly mobilised during bleeding

Extramedually haemopoisis - (make blood outside bone marrow) - pluripotent stem 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 speen. There are even more during infection.

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11
Q

How do you meaure the size of the spleen?

A
  • It is never normal to palpate the spleen below the costal margin.
  • Start to palpate in the right iliac fossa or will miss massive spenomegaly.
  • You feel the spleen edge move towards your hand on inspiration.
  • Feel for the spenic notch.
  • Measure in cm from the costal magin to the mid clavicular line.
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12
Q

Why would the spleen grow?

A
  • Back pressure (portal hypertension in liver disease)
  • Over working red pulp
  • Over working white pulp
  • Reverting to what it used to do (extramedullary haemopoisis.)
  • Extending as infiltrated by cels which shouldn’t be there.
    • Eg cancer cells of blood origin (Leukeimia) or other cancer metastasis
  • Expanding as infiltrated by other material.
    • Eg Gauchers disease or sarcoidosis.
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13
Q

What can cause massive splenomegaly?

A

Chronic myeloid leukaemia, myelofibrosis, maleria, schistosomiasis

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14
Q

Wha could cause moderate splenomegaly?

A

Massive + lymphoma, leukemias, myeloproliferative disorders, liver cirrhosis with portsl hypertension, infections such as glandualr fever causes by Epstein Barr virus.

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15
Q

What could cause mild splenomegaly?

A

Massive + Moderate + Infections such as infectious hepatisis, endocarditis, infiltrative disorder such as sarcoidosis, autoimmune diseases.

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16
Q

What is hyperslenism?

A

Low blood counts can occur due to pooling of blood in the enlarged spleen.

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17
Q

What kinds of things should people with spleenomegaly avoid?

A

Contact sports eg Rugby, Cycling (because of handlebars), Gardening.

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18
Q

What are the complications of splenomegaly?

A
  • Infections - hear splenic rub if listen with stephescope.
  • Rupture causes haematoma.
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19
Q

What is hyposlenism?

A

Lack of functioning splenic tissue.

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20
Q

What are the causes of hyposplenism?

A
  • Splenectomy
  • Sickle cell disease in older children and adults (due to multiple infarcts then fibrosis)
  • Coeliac disease.

A blood film woudl reveal Howell Jolly bodies (DNA remianants).

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21
Q

What are people withhyposplenism at risk of? How do they avoid it?

A

Patients are at risk of overwhelming sepsis, particularly from encapsulated organisms eg Pneumococcus, Haemophilus influenzae and Meningococcus.

Vaccinate against these infections Take like long prophylactic antibiotics.

22
Q

What should a patients Red blood cell count be?

A

4.4-5.9 x 1012 / L

23
Q

What should a patients haemoglobin be?

A

13.5-16.7 g/dl

24
Q

What should a patients Mean Corpuscular Volume (MCV) be?

A

80-100fl

25
Q

What are the functions of red cells?

A
  • Deliver oxygen to tissues
  • Carry Hb
  • Maintain Hb in its reduced (ferrous) state
  • Maintain osmotic equilibrium
  • Generate energy
26
Q

What is the structure of Hb?

A

Tetramer of two paits of globin chains each with its own haem group. They can exist in two confugurations (Oxy and Deoxy)

27
Q

How is Hb synthesised?

A

Globin gene clusters in chromosome 11 and 16 (expressed at different stages of life)

Globin chains synthesised indenendantly and combine to form different haemoglobins.

The switch from foetal to adult Hb occurs at 3-6 months of age.

Foetal and adult Hb and Hb varients have different properties.

28
Q

What is the structure of an erythrocyte cell membrane?

A

The erythrocyte cell membrane is a lipid bilayer that contains proteins such as spectrin, Ankyrin, Band 3 and protein 4.2. These proteins facilitate vertical interactions with the cytoskeleton of the cell which are essential for maintaining the red cell’s biconcave shape and deformability.

Gene mutations in these membrane associated proteins can result in diseases such as hereditary spherocytosis which cause the red cells to lose their biconcave shape.

29
Q

What is haemolytic anaemia?

A

When there are changes in the components of the cell membrane (congenital or acquired), this will change the shape of thw RBC.

This can cause them to be less deformable, more easily broken down and often recognised by the spleen as ‘abnormal’. This means that red cell survival reduced and results in haemolytic anaemia.

30
Q

What can heme catabolism lead to?

A

An excess of red cell destruction can lead toe excess of bilirubin formation which leads to jaundice. This is a sign of haemolytic anaemia.

31
Q

How is Erythropoiesis controlled?

A
  • Patient becomes anaemic so reduced pO2 detected in interstitial cells in kidney.
  • Increased production of Erythropoietin (hormone) by the kidney.
  • Erythropoietin stimulates maturation and release of red cells from marrow.
  • Total red cell and so Hb rises.
  • More O2 delivered
  • Via feedback loop, erythropoietin production falls.
32
Q

What is cytopnia?

A

Reduction in the number of blood cells. It takes on a variety of forms.

33
Q

What are the types of cytopnia?

A
  • Anaemia: Low red cell count.
  • Leucopenia: Low white cell coun
  • Neutropenia: low neutrophil count
  • Thrombocytopnia: Low platelet count
  • Pancytopnia: low RBCs, WBCs and platelets
34
Q

What are …cytosis or …philia?

A

AN increase in the number of blood cells.

35
Q

What are the types of …cytosis or …philia?

A
  • Erythrocytosis: high red cell count
  • Leukocytosis: high white cell count
  • Neutrophilia: high neutrophil count
  • Lymphocytosis: high lymphocyte count
  • Thrombocytosis: high platelet count.
36
Q

What are neutrophils?

A
  • The first responder phagocyte,
  • The commonest white cell,
  • Essential part of the innate immmune system.
  • Short half like (3-4 days)
  • Nucleus = 3-5 lobes.
37
Q

How does neutrophil maturation occur?

A
  1. Myeloblast
  2. Promyelocyte
  3. Myelocyte
  4. Metamyelocyte
  5. Band
  6. Neutrophil
38
Q

How is neutrophil maturation controlled?

A

G-CSF.

  • It increases the production of neutrophils
  • It decreases the time to release of mature cells
  • It enhances chemotaxis
  • It enhances Phagocytosis and killing of pathogens.
39
Q

WHat do we no if a patient needs more neutrophils?

A
  • Doctors will administer recombinant (manafactured) G-CSF
  • For example if a patient has severe neutropenia and sepsis after chemotherapy.
  • Many patients self-inject G-CSF to reduce neutropenia infections post-chemotherapy.
40
Q

What can cause neutrophilia?

A
  • INFECTION!
  • Cancer
  • Acute inflammation
  • Tissue damage
  • Cytokines (G-CSF)
  • Drugs eg steroids
  • Acute haemorrage
  • Metabolic / endocrine disorders
  • Smoking
  • Myoproliferate diseases
41
Q

What would the neutrophil count be in neutropenia?

A

Low.

< 1.5 x109/L

Severe if < 0.5x109/L

42
Q

What are some causes of neutropenia?

A
  • Reduced production,
  • Increased removal or use:
    • immune destruction,
    • sepsis,
    • splenic pooling.
  • Benign ethnic neutropenia,
  • Cyclic neutropenia.
43
Q

What are the causes of reduced production of neutrophils?

A
  • B12 / folate deficiency
  • Infiltration of bone marrow by malignancy or fibrosis
  • Aplastic anaemia
  • Radiation
  • Drugs
  • Viral infections
  • Congenital disorders.
44
Q

What are the consequences of neutropenia?

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

Neurogenic sepsis is a medical emergency. IV antibiotics must be given immediately.

45
Q

What are monocytes?

A
  • Response to inflamation and antigenic stimuli
  • Bluer than neutrophils
  • Macrophages when migrate to tissues
  • lysosomes contain lysozyme, complement, interleukins, arachidoc acid, CSF
  • Phagocytosis and piocytosis
46
Q

Causes of monocytosis?

A
  • Chronic inflammatory conditions: RA, SLE, Crohns, UC
  • Chronic infections eg TB
  • Carcinoma
  • Myeloproliferative disorders / Leukaemias
47
Q

What are Eosinophils?

A
  • 3-8 hours in circulation
  • Lifespan of 8-12 days
  • Responsible for dealing with some parasites
  • Mediator of allergic resonse.
  • Migrate to epithelial surfaces
  • Granules contain arginine, phospholipid, enzymes
  • Phagocytosis of antigen - antibody complexes
  • Mediate hypersensitivity reactions eg to drugs, in asthma, skin inflammation.
48
Q

What are some causes of eosinophilia?

A
  • Allergic diseases (COMMON)
  • Drug hypersensitivity
  • Churg-Strauss
  • Parasitic infection (COMMON)
  • Skin diseases
  • Hodgkin lymphoma
  • Acute lymphoblastic leukaemia
  • Actute myeloid leukaemia
  • Myeloproliferative disorders
  • Eosinophilic leukaemia
  • Ideopathis hypereosinophilic symdrome.
49
Q

What ate basophils?

A
  • Least common but largest WBC
  • Active in allergic reactions and inflammatory conditions.
  • Dense granules, contain: histamine, heparin, hyaluronic acid, serotonin
50
Q

What ate causes of basophillia?

A

Reactive

  • Immediate hypersensitivity reactions
  • Ulterative Colitis
  • Rheumatoid Arthritis

Myeloproliferative

  • CML
  • MPN: ET/PRV/MF
  • Systemic mastocytosis
51
Q

What are the three types of Lymphocytes?

A

Lymphocytes originate in the bone marrow.

B cells - (Humoral immunity) antibody forming cells.

T cells - (cellular immunity) CD4+ helper cells, CD8+ cells

Natural killer cells - (Cell mediated immunity)

52
Q

What are causes of lymphocytosis?

A

Reactive

  • Viral infections
  • Bacterial infection - es Pertussis (Whooping cough)
  • Stress related : MI / cardiac arrest
  • Post splenectomy
  • Smoking

Lymphoproliferative (malignant)

  • Chronic lymphocytic leukaemia (B cells)
  • T or NK cell leukaemia
  • Lymphoma