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General Med 1 > Path - Haem - Exam 2 > Flashcards

Path - Haem - Exam 2 Flashcards

1
Q

Describe the structure of the bone marrow (bone anatomy)

A
  • The spongy bone in which haematopoiesis occurs is a reticulin connective tissue network like spiderweb with Mesenchymal Stromal cells, macrophages and other supportive cells to assist haemopoietic cells
  • Bone marrow is about 50% empty space and 50% cells
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2
Q

Describe the function of the bone marrow (cellular)

A 
• Normal bone marrow function
– production of 
• red cells
• white cells
• Platelets

– Requires
• nutrients including iron, B12, B6, folate, amino acids, energy
• supportive cells- stromal cells, cytokines

Normal bone marrow function
– CYTOKINES-
• Erythroid- includes ERYTHROPOIETIN
• Granulocytes- includes G-CSF, GM-CSF 
• Lymphocytes- Interleukins
• Platelets- THROMBOPOIETIN
• OTHER
– Stromal Cells, Nucleic acids, amino acids etc.
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3
Q

What are cytokine cells and what do they do in haematopoiesis?

A

Cytokines are small proteins that are involved cell signalling

They are released by macrophages, lymphocytes, endothelial cells, fibroblasts and stromal cells, to affect the behaviour of other cells

In haematopoiesis, the presence of different cytokines dictate which cells are produced i.e. erythropoietin will induce the production of erythrocytes

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4
Q

Describe the differentiation of haemopoietic cells

A

HSC –> Common Myeloid Progenitor + Common Lymphoid Progenitor

Myeloid –> Megakaryocyte + Erythrocyte + Myeloblast

Megakaryocyte –> Thrombocytes

Erythrocytes –> RBC

Myeloblast –> Basophil, Eosinophil, Neutrophil, Monocyte

Lymphoid –> small lymphocyte –> T cells + B cells

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5
Q

Characteristics of haemopoietic stem cells

A

Pleuripotent

Displays CD34 on the surface

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6
Q

What are some causes of decreased numbers of RBCs, WBCs and platelets?

A

Red cells
Marrow failure syndromes, Iron/B12/Folate Deficiencies, Blood loss etc. Renal Failure with reduced production of EPO

– White cells
Viral Infections, Post Chemotherapy, Reduced G- CSF stimulation (rare, inherited)

– Platelets
Immune Destruction(ITP), Drugs etc.
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7
Q

What are some causes of increased numbers of RBCs, WBCs and platelets?

A

Red cells
Hypoxia, Renal Tumours- secretion of EPO

• Whitecells
Myeloproliferative disorder, Secondary: Infection, Inflammation

• Platelets
Essential thrombocythaemia, Inflammation, Infection

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8
Q

What are RBCs unable to do since they lack mitochondria and ribosomes?

A

incapable of both oxidative phosphorylation and protein synthesis

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9
Q

What is the diameter or a RBC?

A

7-8um

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10
Q

What are 3 functions of Hb?

A

Oxygen transport (main), carbon dioxide transport (10% of CO2 from tissue to lungs) and NO transport

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11
Q

What chromosome are the alpha and beta globin genes found on?

A

16 and 11 respectively

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12
Q

What is haemoglobin switching?

A

The sequential expression of embryonic, fetal and adult haemoglobin in the developing erythroblast during ontogeny

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13
Q

Describe embryonic switching

A

Embryo (-9wks)

Gower 1: Zeta2E2
Gower 2: a2E2

Fetus (-9wks to +6wks)

HbF - a2y2

Adult: (6 weeks +)

HbA - a2B2 - 96%
HbA2 - a2&2
HbF - a2y2 -

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14
Q

What makes O2 binding to Hb co-operative?

A

Binding of each oxygen enhances binding of the next - Bohr effect

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15
Q

What 3 changes can cause a lower O2 affinity?

A

reduced pH, increased temp and increased 2,3 BPG

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16
Q

What is the advantage of HbF not being able to bind 2,3 BPG effectively?

A

HbF has a higher affinity than HbA for oxygen. Oxygen is preferentially loaded onto HbF in fetal blood from HbA in the mother’s blood

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17
Q

What are the 2 pathways for glucose metabolism in the RBC?

A

Glycolysis and Hexose monophosphate shunt (pentose phosphate pathway)

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18
Q

What is the purpose of the reducing power generated by the HMP shunt?

A

Countering any potential reactive oxygen species that may form from the oxygen carried (OH-, H2O2, HO2, O2-) and the damage to lipids, proteins and enzyme cofactors they would produce. It does this by producing NADP/H and Glutathione

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19
Q

What is methaemoglobin?

A

An oxidised form of Hb with Fe3+ instead of Fe2+. It cannot carry oxygen and precipitates out.

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20
Q

What is the enzyme converting glucose 6P to 6P gluconate?

A

glucose 6P dehydrogenase

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21
Q

How does HMP shunt prevent oxidative stress?

A

Production of large amounts of NADPH that prevents oxidative stress by maintaining glutathione levels. Glutathione is a reducing agent that converts peroxide to water and prevents oxidative damage.

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22
Q

In patients with G6PD deficiency, what oxidising agents may trigger oxidative stress?

A

medications, broadbeans and infections

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23
Q

Why might the anaemia from pyruvate kinase deficiency (most common glycolytic enzyme deficiency) not be as symptomatic as expected?

A

PK def causes loss of membrane pump function and loss of membrane plasticity, leading to usually shaped cells that are destroyed in the spleen. There is also an increase in 2,3-DPG, shifting the haemoglobin curve to the right, allowing greater offloading of oxygen. As a result, only appear slightly anaemic.

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24
Q

What are the 2 crucial structural aspects of the red cell membrane?

A
  1. Must have a lot of it - high SA to volume ratio

2. Must have an effective supporting scaffold/cytoskeleton to prevent membrane loss during day-to-day wear and tear

25
Q

What red cell membranopathy does defects in vertical interactions lead to?

A

Hereditary spherocytosis, as there is a membrane loss causing low SA:V

26
Q

What red cell membranopathy does defects in horizontal interactions lead to?

A

Hereditary elliptocytosis

27
Q

Of all red cell antigens, which system is the most immunogenic?

A

ABO system

28
Q

What is Landsteiner’s rule?

A

Individuals lacking A or B from RBCs will have the corresponding antibody in their plasma - mix of IgM and IgG antibodies

29
Q

What is the time course for ABO antibody production, detection?

A

Production begins after birth, detected by 4-6 months of age and peaks at 5-10 years

30
Q

What is the impact of ABO mismatch?

A

Large scale, rapid destruction of transfused red cells. IgM antibodies activate the complement cascade - 9 plasma proteins. End result is a hole (due to MAC) punched into the donor cells resulting in red cell destruction.

31
Q

Antibodies for the Rh system are ‘naturally formed’. True or false?

A

false

32
Q

When are Rh antibodies formed?

A

Formed upon exposure of negative individuals to Rh positive blood: transfusion or pregnancy (fetus is RhD positive and mother is RhD negative)

33
Q

What produces 2,3-DPG?

A

Glycolysis in RBCs

34
Q

What is ‘band 3’ and what does it do?

A

Band 3 is the most abundant protein in the RBC cell membrane. It is an anion exchanger (Cl-/HCO3-), and is linked to the cytoskeleton for structural integrity. It also has over half of the ABO antigens attached to it

35
Q

How many major phospholipids are in the RBC membrane? Which enzymes maintain the lipid bilayer of the RBC membrane?

A
  • 5 major phospholipids

- Floppases, Flippases and Scramblases

36
Q

What are the ABO antigens?

A

A, B, A.B

37
Q

What are the Rh antigens, and which is the most immunogenic?

A
  • D, C, c, E, e. Over 50 in reality

- D is the most immunogenic

38
Q

What are ABO antibodies?

A

naturally occurring antibodies, produced in response to environmental stimuli

39
Q

What is the nuclear morphology and function of a neutrophil?

A

2-5 segments in nucleus.
Fine granules (primary and secondary)
- phagocytic function
-9-15um diameter

40
Q

What is the nuclear structure and function of an eosinophil?

A

2 lobed nucleus, large round granules.
Weakly phagocytic, involved in allergy and inflammation, kills parasites
-12-17um diameter

41
Q

Name the different types of granular leukocytes

A

Neutrophil, basophil, eosinophil, mast cells

42
Q

What is the nuclear structure and function of a basophil?

A

2 segments in nucleus, purple black granules, large and round.
Involved in allergy, inflammation, parasite response
-12um diameter

43
Q

What is the nuclear structure and function of a monocytes?

A

Horseshoe shaped nucleus, grey cytoplasm, few granules, vacuoles.
Becomes a macrophage, causes phagocytosis, present in chronic infection, involved in processing and presentation of antigen on MHC 2.
Secrete proinflammatory, immunoregulatory, anti inflammatory, and cytokine molecules
15-30um diameter

44
Q

What is the main function of a B cell lymphocyte?

A

Produce antibodies (immunoglobulin/Ig)

45
Q

What is the main role of a T cell lymphocyte?

A

Direct binding of foreign antigens.
Cell mediated immunity
About 70-85% of lymphocytes are T-cells (T:B ratio = 6:1)

46
Q

What is the nuclear morphology of a plasma cell, what is its function, and what cells do these cells originate from?

A

Eccentric nucleus, clumped chromatin, produce monoclonal antibodies & immunoglobulins.
Plasma cells are terminally differentiated B cells

47
Q

What is the structure (nuclear) of a megakaryocyte and what is the function of this cell?

A

Large cell, hyperlobated nucleus, centrally located.

Generates platelets

48
Q

What is the structure and function of a platelet?

A

Anuclear cell fragments that contain cytoplasmic granules. They adhere to and plugs breaches in blood vessel walls AKA they’re involved in clotting cascades

49
Q

Describe the development of a neutrophil, from a myeloid stem cell

A 
Myeloid SC
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Band form
Neutrophil
50
Q

What are some characteristic features of a lymphocyte under a gram stain?

A
  • blue cytoplasm
  • clumped chromatin
  • typically without granules
51
Q

What are some common features of a virus infection in a gram stain? Name some examples of viral infections.

A

Thrombocytopenia - low platelet count
Reactive T cells - increased size, basophilic cytoplasm

Examples of viral infection: Epstein-Barr Virus EBV, cytomegalovirus CMV, varicella, Viral Hepatitis, Dengue fever, Parvovirus

52
Q

How many bacterium can neutrophils and macrophages phagocytose?

A

N: 3-20
M: up to 100

53
Q

What are some characteristic features of a lymphocyte under a gram stain?

A
  • blue cytoplasm
  • clumped chromatin
  • typically without granules
54
Q

What are some common features of a virus infection in a gram stain? Name some examples of viral infections.

A

Thrombocytopenia - low platelet count
Reactive T cells - increased size, basophilic cytoplasm

Examples of viral infection: Epstein-Barr Virus EBV, cytomegalovirus CMV, varicella, Viral Hepatitis, Dengue fever, Parvovirus

55
Q

Outline the process of EBV driven lymphoma formation

A

EBV proliferates in B cells and then turns off its antigens to evade the immune response. In immunocompromised hosts, the virus selects abnormal B cells which proliferate to form a lymphoma

56
Q

What are some of the features of Bordetella pertussis infection on a gram stain? What’s the common name for the infection?

A

Lymphocytosis - increased lymphocytes due to a lymphocyte promoting factor secreted by the bacteria that inhibits lymphocyte migration to the tissues
Leucocytosis - indicates infection

Common name is Whooping Cough

57
Q

What is haemophagocytosis? How does it alter blood cells (in terms of their count)? What infections is it associated with?

A

Macrophages phagocytose haemopoietic cells in the bone marrow

Causes pancytopenia - cytopenia all multiple cell types (leucopenia, anaemia, thrombocytopenia)

Associated with any infections - viral (EBV, CMV, varicella), bacterial, fungal, protozoal

58
Q

Name 3 characteristics of parvovirus in a gram stain.

A

Anaemia - caused by reduced erythropoiesis

Giant erythroblasts with viral inclusions

Reticulocytopenia

NOTE: not parvovirus is anaemia but no Reticulocytopenia

59
Q

On a gram stain, what features would indicate bacterial infection?

A

Neutrophilia - increased neutrophils (note: neutropenia is seen in sepsis)

Left shift - increased immature/precursor cells
Toxic granulation - neutrophils contain more granules

Dohle bodies - remnants of ER in the cytoplasm of neutrophils (look like blue inclusions)

Vacuolation- increased vacuoles in neutrophil cytoplasm

Rouleaux- stacking of rbc caused by increased immunoglobulins

Thrombocytopenia - low platelet count

Hypercellular bone marrow - ready to release lots of precursors

Granulomas in the bone marrow

General Med 1 (24 decks)

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