Lecture 6 - Haemopoiesis Flashcards
(37 cards)
1
Q
Where does haemopoiesis occur in an adult?
A
- Bone marrow
- Axial skeleton in an adult: pelvis, sternum, ribs, vertebrae
- In neonates: entire skeleton
2
Q
Where is erythropoietin and thrombopoietin secreted from? What is their function?
A
- Erytropoietin secreted by kidney stimulates RBC prod.
- Thrombopoietin secreted by liver and kidney stimulate platelet prod
3
Q
What is the Reticuloendothelial system? Main organs? Function?
A
- Part of immune system, made up of monocytes in the blood
[Kupffer cell in liver, microglial in CNS, langerhans in skin] - Major organ is spleen and liver
- Function: remove dead/dmg cells and destroy foreign antigens
4
Q
Function of the spleen in adults
A
- Phagocytosis of old RBC
- Blood pooling: platelets n RBC rapidly mobilised during bleeding
- Extramedullary haemopoiesis: pluripotent stem cells proliferate when bone marrow fails (myelofibrosis)
- Immune function: contain B and T cells
5
Q
Diff of white and red pulp in spleen
A
- Red pulp: red cells pass thru, identify old RBC
- White pulp: WBC & plasma pass thru, stimulate immune response
6
Q
Causes of splenomegaly
A
- Portal hypertension in liver disease (reduced blood flow to liver –> build up in spleen)
- Overwork
- Extramedullary haemopoiesis
- Cancer metastasised
- Granuloma (tiny cancer)
7
Q
Splenomegaly can be categorised into diff. ranges (massive –> mild) give one eg of each. What can splenomegaly cause?
A
- Massive: myelofibrosis & chronic myeloid leukemia (result in extramedullary haemopoiesis) or malaria
- Moderate: lymphoma, liver cirrhosis w portal hypertension, glandular fever
- Mild: infection, endocarditis (inflammation of heart chamber valves)
- Splenomegaly can be subset of hypersplenism –> low blood count due to pooling of blood
- Spleen high vascular –> rupture –> death by exsanguination –> avoid contact sports
8
Q
What are the causes of hyposplenism?
A
- Splenectomy (due to splenic trauma/cancer)
- Sickle cell disease
- GI disease (Chron’s/coeliac)
- Autoimmune disease (RA, Hashimoto, systemic lupus)
9
Q
Presence of what in blood confirms hyposplenism? What are patients with this condition at risk of? What should be done to reduce the risk?
A
- Howell Jolly bodies: RBC w DNA remnants
- Will normally be removed by fully functioning spleen
- Risk of sepsis from encapsulated bac. (streptococcus pneumonia/meningococcus) –> immunised and lifelong prophylactic antibiotics
10
Q
Function and structure of RBC
A
- Function: deliver O2 to tissue, maintain Hb in reduced (ferrous) state
- Biconcave, no nucleus, no mitochondria, no DNA
- 2α, 2β globin chains (Ch 11 & 16)
11
Q
What do changes in RBC membrane structure result in?
A
- RBC less deformable/more fragile
- Removed by spleen –> haemolytic anaemia
12
Q
What are the proteins involved in hereditary spherocytosis? Mode of inheritance? And their functions?
A
- Spherocytosis is due to mutation in one of the proteins
- Autosomal dom.
Say Anything Before Popping
1. Spectrin: actin crosslinking (most common)
2. Ankyrin: links integral membrane proteins to spectrin-actin cytoskeleton
3. Band 3: facilitates chloride and bicarbonate exchange across membrane
4. Protein 4.2: ATP-binding protein regulate association of band 3 w ankyrin
13
Q
What are neutrophils (func. and structure)? What hormone controls their maturation from myeloblast?
A
- Most common phagocyte, part of immune system
- Has 3-5 lobed nuclei
- Maturation controlled by hormone G-CSF (glycoprotein growth factor and cytokine):
1. Increases prod. of neutrophils
2. Speeds up release of mature N from BM
3. ⬆️phagocytosis and chemotaxis
14
Q
How is recombinant G-CSF used clinically?
A
- Controls neutrophil growth
- Administered to patins when more neutrophils are needed: neutropenia/sepsis (AFTER CHEMOTHERAPY)
15
Q
What is neutrophilia and its causes?
A
- Increase in no. of circulating neutrophils
- Caused by: infection, tissue dmg, myeloproliferative diseases, cytokines (G-CSF), haemorrhage (decrease in overall blood vol, ⬆️circulating WBC)
16
Q
What are the consequences of neutropenia?
A
- Life threatening bac./fungal infection
- Mucosal ulceration (mouth ulcers)
- Neutropenic sepsis (med. emergency) –> immediate intravenous antibiotics!!
17
Q
What are the causes of neutropenia?
N.B Only cells in circulating pool are calculated in blood count
A
- Reduced production:
- B12/folate deficiency
- Viral infection (very common)
- Infiltration (myelofibrosis)
- Aplastic anaemia (empty marrow) - Increased removal/use:
- AI
- Sepsis (move to tissues, X maintain enough no.)
- Splenic pooling
18
Q
What are (structure and func.) monocytes?
A
- Largest cell in blood (irregular cell shape, kidney lobe)
- Develop into macrophages/dendritic cells
- Antigen presenting role/phagocytosis –> protect against bac. infection
NEB is granulocytes
19
Q
What are some causes of monocytosis?
A
- Bacterial infection (TB)
- Inflammatory conditions (RA)
- Myeloproliferative disorders/leukemia
20
Q
What are (structure and func.) eosinophils?
A
- Immune response against parasites (Helminths)
- Mediate allergic response
- Inapp. activation leads to tissue dmg/inflammation (asthma)
- 2 lobe (C), granular (contains elastase)
21
Q
What are some causes of eosinophilia?
A
- Common: allergies (asthma, eczema); parasitic infection (tape worms); drug sensitivity; Churg-Strauss (AI inflammation of blood vessels)
- Rare: acute lymphoblastic leukaemia; acute myeloid leukaemia; myeloproliferative conditions
22
Q
What are (structure and func.) basophils?
A
- Least common and very large
- Active in allergic/inflammatory conditions
- Large dense granules (very black dao X see nucleus) containing histamine (⬆️permeability of blood vessels) and heparin
23
Q
Causes of basophilia?
A
- Hypersensitivity reactions
- RA
- Myeloproliferative diseases
24
Q
Type of lymphocytes. Causes of lymphocytosis?
A
- T cells, B cells, natural killer cells
- Deeply staining nucleus and a relatively small amount of cytoplasm
- ⬆️reaction: viral infection, bac. infection, post splenectomy
- Lymphoma, chronic lymphocytic leukemia
25
Summary of shapes
WBC Shape (nucleus)
Neutrophils Multinucleated (3-5) (granulocyte)
Eosinophils Bi-lobed (granulocyte)
Monocytes Kidney shaped (very black)
Basophils Bi-lobed or tri-loped (granulocyte)
Leucocyte Big circle, lighter than monocyte
26
Which layer of human blood centrifuged will you expect to find neutrophils?
- "Buffy coat": thin layer of cells between plasma and the red cells (<1% total blood vol)
- Contains most WBC and platelets
27
Which artery supplies the spleen?
Splenic artery (branches from celiac artery) goes to pancreas
28
Approximately when does the switch from fetal to adult haemoglobin occur?
3-6 months of age
29
She has lost 1 litre of blood since giving birth 6 hours ago and now has an increased heart rate, increased breathing rate and feels faint upon standing.
What finding would be likely in a full blood count from this woman in her current condition?
- Neutrophilia
- A full blood count can only measure the circulating pool of neutrophils. An acute haemorrhage brings more neutrophils from the marginated pool and into the circulating pool thus leading to neutrophilia.
30
Desc degradation of haem
- Haem --> bilirubin (unconjugated leads to jaundice) --> bilirubin (taken up by liver, conjugated w glucuronic acid) --> secreted in bile
- Urobilinogen oxidised to stercobilin --> faeces
- Urobilinogen --> urobilin --> urine
31
Why would there be errors in lab results when doing a blood count?
- Mix up specimen
| - Pooling samples (mix one tube contents w other)
32
Desc Packed Cell Vol (PCV)/ Haematocrit (Hct). Used to assess what?
- Proportion of blood that is made up of RBC
(centrifuged)
- Asses polycythaemia (high conc of RBC in blood)
[treatment = venesection or drug treatment]
- Assess anaemia (depressed haematocrit)
33
What does plasma, buffy coat and haematocrit contain?
- Plasma: water, proteins, hormones
- Buffy coat: platelets, WBC
- Haematocrit: RBC
34
What is red cell count? What is it used to assess?
- No. of RBC in given vol. of blood
- Assess microcytic anaemia:
i) reduced in iron deficiency
ii) increased in thalassemia trait
- Erythrocytosis: if polycythaemia due to decreased plasma vol, RCC X ⬆️
35
What is mean cell volume? Used to assess what?
- Avg. vol. of red cells
- Determine whether macro/micro anaemia
- Increase in: haemolytic anaemia (large size of reticulocytes), liver disease
- Decrease n: thalassemia, anaemia of chronic disease
36
What is Red Cell Distribution?
- Measure variation in size of RBC
- If increased = anisocytosis (unequal size of RBC)
- Assess timeline of anaemia
37
What is mean cell hb?
- Avg. measure of Hb in RBC
| - Increased in macrocytic anaemia, reduced in thalassemia
