Lecture - Blood - Leucocytes and Pathology

Question 1

What do these look like under the microscope:

1. Neutrophil
2. Eosinophil
3. Lymphocyte
4. Monocyte
5. Basophil
6. Band form

Answer 1

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Question 2

What does normal bone look like?

Answer 2

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Question 3

So you have a pluripotent stem cell…what are the two things derived from that and what do each make?

Answer 3

Pluripotent stem cell makes lymphoid stem cell and myeloid stem cell. Then you get the myeloid series from than and the lymphoid series

Lymphoid series:

• T lymphocyte (mature in thymus)
• Natural killer cell
• B cells (form plasma cells which produce AB, I think)

Myeloid series:

• Erythrocyte
• Megakaryocyte (forms platelets for clotting)
• Monocyte (forms macrophage)
• Granulocytes

Question 4

Describe the myeloid/neutrophil maturation in bone marrow

Answer 4

First you have the myeloblast - that’s where you have the rapid cell division. You have a basophilic cytoplasm (purple kinda) and lots of RNA hence the blue?

Then the PROMYELOCYTE. Here you also get rapid cell division, primary granules and even more cytoplasm

After that the myelocyte - stop growing here, maturations occurs and get secondary granules

Then the metamyelocute - get nucleus indented

Band neutrophil/neutrophil - this Is where you have the nucleus lobed.

Question 5

What are the kinetics of granulopoiesis?

Answer 5

First you have stem cells and they form diving cells (myeloblasts + premyelocyes) and then they mature into myelocytes, band forms and polymorphs (don’t divide - just mature). These mature cells will then circulate or marginate (half and half). The marginated cells will go into tissue and become granulocytes. Throughout this, you have growth factors like GM-CFS and G-CSF which make it happen. They stand for granulocyte (monocyte for M) colony stimulating factor

Question 6

Neutrophils:

1. What three things do they do?
2. How do they adhere and marginate?
3. What are neutrophil NETs? Like what’s NETosis?

Answer 6

1. They search, ingest and destroy bacteria
2. They adhere due to adhesions on endothelial cells like selectins and roll along. For slow rolling, you have selectins and integrins. and then when you have inflammation, they’ll transmigrate and then kill the bacteria.
3. Neutrophil Extracellular Traps - they form by the release from neutrophils of decondensed chromatin that is covered with antimicrobial components to trap bacteria so doesn’t spread.

Question 7

hat is neutrophilia and how does it happen?

What are reactive neutrophil changes in severe infection?

Answer 7

It is increased neutrophils.

Causes:
1. Infection and inflammation (will have fever, shift to immaturity of neutrophils (‘shift to left’) and toxic change in severe infection

2. Drug-induced: some drugs produce demmargination so you’ll increase neutrophils in blood
3. Smoking, acute stress (heart attack) and others

Reactive neutrophil changes in severe infection is like:
-Toxic granulation: increased number of prominent granules
-Vacuolation: autophagocytosis
-Dohle body: pale blue inclusion (RER)
=These are very important sign that there is something severe going on with the patient

Question 8

What is neutropenia and what are the causes?

What are the numbers and what do you do with wild/severe?

Answer 8

It means you have less neutrophils. Like, they’re below the ref range

1. It can happen bc part of a pancytopenia (any sort of disease which reduces the blood cell count) such as a side effect of chemotherapy is that.
2. Could be drug-side effect such as it might supress marrow or it might beAB meditated (metabolites from drug bind the membrane of neutrophil and that causes AB to be produced against the neutrophil).
3. Could be a viral infection like glandular fever
4. Could be genetic or to do with ethnicity
5. Fulminant bacterial infections: All the neutrophils get used up before the barrow can respond - bacterial infection been that severe.

Mild: 1-1.9

• not clinically important
• could be medical history, ethnicity or viral infection
• use blood count and blood film

Severe: Less than 0.4

• watch closely for fever
• consider protective isolation
• occasionally treat with G-CSF (growth factor for neutrophils)
• might be no pus in bacterial infection

Question 9

What will these do to neutrophils:

1. Diabetes
2. Alcoholism
3. Renal failure
4. Steroids

Genetic

Answer 9

1. Will impair phagocytosis and killing
2. Same as above so more susceptible to infections
   3, Impair phagocytosis
3. Steroids cause neutrophilia by causing demmargination (by softening cytoskeleton_ so neutrophils are less able to adhere and fail to egress into tissues

Genetic: there might be defects in neutrophil function
-these affect many of the functions but are very rare

Question 10

Eosinophilia

1. What is it associated with (2) and what stimulates eosinophil production
2. Small print - what else is associated with it?
3. Activated eosinophil are what and promote what?
4. Does eosinophil promote immunity?

Answer 10

1. It’s associated with parasitic infection and allergic reactions (including drug reactions). You have IL-5 from T cells, mast cells and macrophages which stimulates eosinophil production
2. Some auto-immune conditions and many rare blood cancers are associated with it
3. Activated ()s are antiviral and promote survival from an otherwise lethal respiratory virus infection (in mice, anyway)
4. It’s been questioned

Question 11

Monocytes:

1. What do they become in tissues?
2. Give some examples.of what they’re called in different organs
3. What percentage of cells do they make up in organs?
4. What are the two main causes of monocytosis? (increase in monocytes)

Answer 11

1. They become macrophages (phagocytes) in tissue.
2. Like in CT, they’re histiocytes, Langerhan’s cells in skin, osteoclasts in bone etc
3. Make up 10-15% of cells in every organ
4. There are two main causes:
   - Reactive chronic inflammatory states: chronic bacterial infections e.g. untreated pneumonia, TB etc
   - Myelodysplastic syndrome: have a weird growth in bone

Question 12

Basophils:

1. What two things do they do?
2. Is the basophil count useful clinically?

Answer 12

1. Immunity against words, regulates chronic allergic inflammtion
2. No

Question 13

1. What is leukoerythroblastic anaemia?

2. What are causes for it?

Answer 13

1. When you have marrow full of cancer so you get immature cells in blood like myelocyte, tear drop red cells and nucleated RBC in blood film
2. Things that can push cells out are: marrow replacement from leukaemia or lymphoma. Marrow infiltration by metastatic cancer annnnnd myelofibrosis (a marrow cancer)

Things that can pull the cells out are severe hypoxia + infection (e.g. pneumonia): We see it bc infection (left shift) and also see early red cells bc hypoxic from pneumonia

Question 14

1. What are the three main lymphocytes in blood?

2. How is lymphocytosis caused at varying ages?

Answer 14

T, B and NK cells

2. Children: viral infections, pertussis, acute lymphoblastic leukaemia (ALL)

YA’s: EBV (glandular fever)

Any age: CMV, acte HIV

Elderly: Chronic LL

Question 15

Glandular fever - acute EBV infection.

1. What cells does it infect?
2. What are the large atypical lymphocytes in blood?
3. Are monocytes affected?
4. What are some symptoms?

Answer 15

1. B
2. Reactive T cells
3. No
4. Fever, sore that, enlarged spleen

Question 16

Malignant disease

1. What does cancer reflect?
2. It is c____ p_____
3. Can be due to genetic mutations that
4. A malignant tumour may replace _______ ______ and infiltrate into other ______, replacing and destroying normal
   cells.

Answer 16

1. It reflects loss of normal response to regulatory signals for growth, differentiation and death
2. It is clonal proliferation
3. Can be due to genetic mutations which:
   - enhance growth signals
   - disrupt growth regulators
   - prevent cell death

A malignant tumour may replace normal marrow and infiltrate into other tissues, replacing and destroying normal
cells.

Question 17

What are the three myeloid cancers and how are lymphoid different?

Answer 17

Read that