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MEH > Haemopoiesis, bone marrow and spleen > Flashcards

Haemopoiesis, bone marrow and spleen Flashcards

1
Q

Where does haemopoiesis occur?

A

Bone marrow of the axial skeleton and skull in adults
(Extensive throughout the skeleton in infants)

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2
Q

What determines the differentiation of haemopoietic stem cells?

A

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

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3
Q

Which hormone stimulates RBC production and what is it secreted by?

A

Erythropoietin - secreted by kidney

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4
Q

Which hormone regulates platelet production and what is it secreted by?

A

Thrombopoietin - secreted by kidney and liver

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5
Q

In pathological conditions like myelofibrosis or thalassaemia, where does haemopoiesis occur?

A

Haemopoietic stem cells can migrate into circulating blood and colonise in other tissues. EXTRAMEDULLARY HAEMOPOIESIS occurs in tissues where haemopoiesis previously occurred in early life (e.g. spleen or liver)

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6
Q

How are dead or damaged blood cells removed?

A

The reticuloendothelial/ lymphatic system is part of the immune system and is made of monocytes and tissues with phagocytic cells. Main organs involved are spleen and the liver.

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7
Q

What are the two major parts of the spleen and what are their functions?

A
  1. Red pulp: sinuses lined by endothelial macrophages - identify abnormal cells or foreign antigens and move it to white pulp
  2. White pulp - similar to lymphoid follicles and contains lymphocytes that can trigger an immune response
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8
Q

What are the functions of the spleen? (4)

A
  1. Identifying and removing old/abnormal red cells
  2. Mobilising blood pooling platelets and RBCs during bleeding
  3. Extramedullary haemopoiesis - pluripotent stem cells proliferate during haematological stress or if bone marrow fails
  4. Immunological function - 25% of T-cells and 15% of B-cells reside in the spleen
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9
Q

How does blood enter, pass through and leave the spleen?

A

Blood enters via the splenic artery
- White cells and plasma preferentially pass through the white pulp
- Red cells preferentially pass through the red pulp
Blood leaves via the splenic vein which joins the portal vein

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10
Q

Why can splenomegaly occur? (5)

A
  1. Portal hypertension - tension in portal vein builds back pressure in splenic vein so blood cannot leave the spleen at a normal rate
  2. Overwork of red or white (high abnormal cells leads to higher removal rate)
  3. Extramedullary haemopoiesis
  4. Expansion caused by infiltrated cells (cancer cells of blood origin e.g. leukaemia or cancer metastases)
  5. Expanding as infiltrated by other material (granulomas)
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11
Q

How would you examine the spleen?

A

Spleen should not be found below the costal margin
Start to palpate in RIGHT ILLIAC FOSSA and move up to the LEFT HYPOCHONDRIAC region - and feel the splenic notch

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12
Q

What are patients with splenomegaly at risk of?

A

Splenic rupture - enlarged spleen is not protected by the rib cage
patients must avoid contact sports and vigorous activity

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13
Q

What are the impacts of splenomegaly/ hypersplenism on blood counts?

A

Low blood counts - low white cell, red cell and platelet count. Occurs due to pooling of blood in the spleen

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14
Q

What is hyposplenism and what are its causes? (4)

A

Lack of functioning splenic tissue caused by:
1. Splenectomy
2. Sickle cell disease: causes infarcts in the spleen and fibrosis
3. GI diseases (Coeliac and Crohn’s disease; ulcerative disease)
4. Autoimmune disease: systemic lupus, RA, Hashimoto’s disease

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15
Q

What are patients with hyposplenism are risk of?

A

Sepsis/infections from encapsulated bacteria
E.g. Neisseria meningitis, Haemophilus influenzae, Sterptococcus pneumonia (NHS)

Patients are immunised and given lifelong antibiotic prophylaxis

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16
Q

What can be observed in blood films of patients with hyposplenism?

A

Howell Jolly inclusion bodies - red cells contain inclusion bodies (appear as dark spots inside cells) which are usually removed by the spleen. These inclusion bodies are remnants of the nucleus (DNA remnants)

17
Q

What are the functions of erythrocytes?

A

Carry O2 to tissues
- carry Hb
- maintain Hb in its reduced/ferrous state (Fe2+)
- maintain osmotic equilibrium
- generate energy

18
Q

What are structural features of Hb?

A
  • It is a tetramer of 2 pairs of globin chain and each chain has its own haem group
  • Globin gene clusters in C-some 11 and 16
  • Different globin chains combine to form different Hb with different properties
  • Switch from fetal to adult Hb at 3-6 months
  • Hb exists in oxyHb or deoxyHb forms
19
Q

Which proteins are involved in maintaining the RBC membrane structure?

A

Spectrin: actin crosslinking and molecular scaffold protein that link PLASMA membrane to the ACTIN CYTOSKELETON (alpha and beta spectrin)

Ankyrin: Links integral membrane proteins to the underlying spectrin-ankyrin cytoskeleton

Band 3: allows chloride and bicarbonate exchange across membrane and links membrane to the cytoskeleton by binding to ankyrin and protein 4.2

Protein 4.2: ATP-binding protein that regulates the binding of band 3 to ankyrin

20
Q

Describe the degradation of haem

A
  1. Senescent red blood cells are engulfed by macrophages in RES
  2. Once broken down, Fe2+ is released into circulation to be recycled
  3. Haem is then broken down to unconjugated bilirubin
  4. Unconjugated bilirubin is transported to liver to be conjugated (excess can cause jaundice)
  5. The liver conjugates bilirubin with GLUCORONIC ACID to produce bilirubin diglucoronide
21
Q

How does the liver conjugate bilirubin? What is conjugated bilirubin called?

A

With glucoronic acid
Bilirubin diglucoronide

22
Q

How is conjugated bilirubin processed and disposed?

A
  • Bilirubin glucoronide is secreted in bile into the duodenum
  • Glucoronic acid is removed by bacteria in the gut and bilirubin is converted to urobilinogen which is oxidised to stercobilin
  • Stercobilin is disposed in faeces
  • Some urobilinogen is absorbed into blood, transported to kidney and is oxidised to urobilin -> excreted in urine
23
Q

What does ‘cytopenia’ mean?

A

reduction in the number of cells

24
Q

What does ‘cytosis’ or ‘philia’ mean?

A

increase in the number of cells

25
Q

What is an i) increase and ii) decrese in number of paltelets known as?

A

i) thrombocytosis or thrombocythaemia
ii) thrombocytopenia

26
Q

What is an i) increase and ii) decrease in all type of blood cells known as?

A

i) panmyelosis
ii) pancytopenia

27
Q

What is an i) increase and ii) decrease in RBCs known as?

A

i) polycythaemia or erythtocytosis
ii) anaemia

28
Q

How do neutrophils appear histologically and what are their functions?

A
  • They have a multilobular nucleus (appears segmented) which are linked by threads of highly condensed chormatin
  • First-responder phagocyte
  • Most common white cell
  • Essential part of innate immune
    system
  • Circulate in bloodstream & invade
    tissues – live for 1-4 days
29
Q

Which hormone controlls the maturation of neutrophils?

A

G-CSF is a glycoprotein growth factor & cytokine which:
* Increases production of neutrophils
* Speeds up release of mature cells from BM
* Enhances chemotaxis
* Enhances phagocytosis and killing of
pathogens
Recombinant G-CSF is administered in cases of low neutrophils (neutropenia and sepsis after chemotherapy)

30
Q

What are the 2 main causes of neutropenia?

A
  1. reduced production in bone marrow due to B12/folate deficiency, drugs (chemo, antibiotics etc), viral infections etc..
  2. increased removal or use - autoimmune destruction, sepsis, splenic pooling
31
Q

What are the causes of neutophilia?

A

Infection
Myeloproliferative diseases
Tissue damage
High cytokines (G-CSF)

32
Q

What are monocytes important for and how do they carry out this function?

A

Important in defence against chronic bacterial infections.
They phagocytose microorganism and breakdown/remove debris and present it to lymphocytes

33
Q

What are the causes of monocytosis?

A
  • Bacterial infection e.g. tuberculosis
  • Inflammatory conditions e.g. rheumatoid arthritis, Chron’s
    Ulcerative colitis
  • Carcinoma
  • Myeloproliferative disorders and Leukaemias
34
Q

What is the major role of eosinophils and how do they carry out this function?

A
  • Responsible for immune
    response against multicellular
    parasites and a mediator of allergic responses.
  • Granules contain cytotoxic proteins which aid breakdown after phagocytosis
  • Inappropriate activation leads to tissue damage and inflammation (asthma)
35
Q

What are the causes of eosinophilia?

A

Common: allergic diseases (asthma, eczema), parasitic infection, skin diseases, drug hypersensitivity

Rare: Hodgkin lymphoma, eosinophilia or acute myeloid leukaemia

36
Q

Give 2 histological features of basophils and what is their function?

A
  • Least common and large
  • Granules stain deep blue or purple and mask the nucleus
  • Active in allergic reactions and inflammatory conditions
  • Dense granules contain histamine, heparin, hyaluronic acid and serotonin
37
Q

When does basophilia occur?

A
  1. Reactive conditions: Immediate hypersensitivity reactions, Ulcerative Collitis, Rheumatoid Arthritis
  2. Chronic myeloproliferative diseases (where bone marrow makes too many blood cells): systemic mastocytosis, myeloproliferative neoplasms (cancer in bone)
38
Q

What do lymphocytes give rise to?

A

B cells, T cells (CD4+ helper cells; CD8+), natural killer cells

39
Q

When does lymphocytosis occur?

A

Reactive conditions:
* Viral infections
* Bacterial infections-especially
whooping cough
* Stress related: MI/cardiac arrest
* Post splenectomy
* Smoking

Lymphoproliferative (malignant):
* Chronic Lymphocytic Leukaemia (B
cells)
* T- or NK- cell leukaemia
* Lymphoma (cells ‘spill’ out of
infiltrated bone marrow)

MEH (2 decks)

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