lecture for week 3

Question 1

what is the primary function of red blood cells

Answer 1

oxygen exchange in the tissues
lifespan of 120 days

Question 2

what is the primary function of WBC

Answer 2

perform immune functions
(or fight infection)

Question 3

what is the primary function of PLATELETS

Answer 3

play a role in maintaining hemostasis

Question 4

what is hemostasis

Answer 4

regulated process of blood cell production that includes cell
renewal, proliferation, differentiation and maturation”

Question 5

What is a hematopoietic stem cell capable of

Answer 5

it is self renewing
-if it is undifferentiated it is called pluripotent
-differentiation occur with the help of cytokines which help the HSC to become progenitor stem cell - either MYELOID OR LYMPHOID
-these cells then further differtiate with the help of cytokines to become precursor cells giving rise to the first morphologically recognizable blood cells

Question 6

what is the cell lines of myeloid progenitor cell

and what is the precursor

Answer 6

Granulocytes (Neuts, Eos, Baso)
‒Monocytes
‒RBC
‒Platelets

-Myeloid Stem Cell precursor CFU-GEMM

Question 7

what is the cell lines of Lymphoid progenitor cell and what is the precursor

Answer 7

‒Lymphocytes (T-cells & B-cells)
-precursor CFU-L

Question 8

what are cytokines

Answer 8

● Soluble proteins secreted by cells which act as mediators, controlling functional activities of other cells – regulators

• growth factors, Colony Stimulating Factors (CSF) and Interleukins (IL)

Question 9

what is GM-CSF

Answer 9

-cytokine that stimulates growth of granulocyte/monocyte colonies

Question 10

what is Erythropoietin/EPO

Answer 10

stimulates proliferation of erythroid progenitors and prevents apoptosis of CFU-E

Question 11

what is the Mesoblastic or Yolk Sac Phase

1ST STAGE of Hematopoietic
Development

Answer 11

-Haematopoiesis begins around 19th day of gestation with only primitive RBCs (erythroblasts) and blood vessels being produced
-hba1c is also being produced by erythroblasts to deliver oxygen to tissues
-occurs intravascularly
-cells migrate from mesoderm to yolk sac

Question 12

what is the Hepatic Phase

2ND STAGE of Hematopoietic
Development

Answer 12

-Beings at 5 to 7 weeks gestation in liver and spleen
‒ Continues in thymus, placenta, kidney, lymph nodes, and bone
marrow
RBCs, Granulocytes, and Monocytes produced
* Lymphoid cells produced
* Megakaryocytes produced - PLATELETS
-occurs extravascularly
-hematopoiesis in AGM region and yolk sac region disappear in this stage
-peak at 3 months
-thymus is first fully formed organ in fetus - T cell production
-spleen and kidney - b cells
-HB F dominant hem

Question 13

what is the Medullary (Myeloid) Phase

3rd STAGE of Hematopoietic
Development

Answer 13

Beings between 4th and 5th months gestation
‒ Active site is in medullary cavity
‒ Cells at various stages of maturation can be seen in all blood cell lineage
-By end of 6th months gestation and at birth, bone marrow is
the primary site of Hematopoiesis
- HSCs and mesenchymal cells go to the core of the bone to differentiate into structural elements like stromal cells
- can measure EPO, G-CSF, GM-CSF

Question 14

what is Medullary & Extramedullary Hematopoiesis

Answer 14

Adult Hematopoietic Development
Hematopoietic tissue located:
‒ Bone marrow (primary site)
‒ Lymph nodes
‒ Spleen
‒ Liver
‒ Thymus
* Bone marrow contains developing erythroid, myeloid, megakaryocytic, and lymphoid cells
* Primary lymphoid tissue – Bone marrow and thymus
* Secondary lymphoid tissue – Spleen, lymph nodes, and MALTs (mucosa associated lymphoid tissue)

Question 15

Normal Bone marrow contains
two major components

Answer 15

1. Red marrow Haematopoietically active (at birth it is primarily red)
2. Yellow marrow Haematopoietically inactive

As child matures, adipose replaces hematopoietic cells in bone marrow
* Red marrow converted to Yellow marrow and the conversion continues on with aging

Question 16

Adult Axial Skeleton contains what

Answer 16

The adult skeleton contains:
* 80 bones found in the head and trunk
* Active RED marrow (RBC production) located in:
‒ Skull
‒ Sternum
‒ Vertebrae
‒ Ribs
‒ Pelvis
‒ Proximal ends of the long bones
* Remainder is Yellow marrow
* Normal adult Red Marrow still contains fat known as Marrow cellularity = ~ 50:50 active cells: adipose

• During times of increased demand on bone marrow for blood cells
  ‒ Yellow marrow can revert to Red (or active) marrow
  o Hematopoietic cells replace adipose tissue in bone marrow - E.g., Seen in disease states, severe infections, hemolysis or excessive blood loss

Question 17

what is Abnormal Hematopoiesis

Answer 17

When BM is overwhelmed or damaged, hematopoietic tissue in other organ sites can resume blood cell production – this is called Extramedullary Hematopoiesis
* Includes sites:
‒ Liver
‒ Spleen
‒ Thymus- secondary site for lymphoid tissue
‒ Lymph nodes

Question 18

describe a compact bone

Answer 18

Compact bone consists of:
* Cortical outer layer
* Cavities or Trabecular (cancellous) bone – interconnecting boney struts (trabeculae) that look like honeycomb
* Intervening spaces contain hematopoietic tissue (red marrow), adipose (yellow marrow), and numerous blood vessels, all in close contact

Question 19

retrogression

Answer 19

as you get older red marrow is replaced with yellow (adipocytes)

Question 20

Describe two types of normal BM

Answer 20

1. Red
   * Haematopoietically active areas in certain bones
   * Marrow arranged in ‘extravascular cords’ found between vasuclar sinuses and trabeculae of compact bone
2. Yellow
   * Haematopoietically inactive
   * Composed primarily of adipocytes (fat cells)
   * Yellow marrow is scattered within areas of red marrow

Question 21

what are Hematopoietic Cords - in red marrow

Answer 21

Extravascular tissue containing all developing blood cell lineages
-cords are where HSCs develop their niches
-megakaryocytes are located beside the walls of vascular sinuses to allow release of platelets into sinus lumen
-as granulocytes mature they move closer to the vascular sinuses
-endothelial cells (stromal cell) regulate flow of cells leaving and entering the sinuses
-adipocytes (stromal cell) -, release cytokines, have single fat vacuole and play role in regulating the volume of BM in which hempato occurs
-adventitial cells (stromal cell) - form layer of cells of vascular surface like a lattice

Question 22

what does an H&E-Stained Bone Marrow Biopsy look like

Answer 22

Hematopoietic tissue consists of the following ‘areas’:
‒ Erythropoiesis- cells with darker staining nuclei
‒ Granulopoiesis- lighter staining cells
‒ Adipocytes- do not stain (blank spaces nothing for the stain to anchor to)
‒ Adventitial cells and their processes (support and help to anchor developing blood cells)
‒ Blood vessel(s)

normal bone marrow will show 50-50 marrow to fat

Question 23

how does circulation work in the bone marrow

Answer 23

• nutrient and o2 requirements fulfilled by nutrient (blood only) and periosteal arteries (nutrients for osseous bone and marrow) entering via foramina
• Blood leaves BM by the central longitudinal vein
  -mature cells leave the extravascular space for the PB through venous sinusoids (adventitia, basement membrane and endothelial lining of sinusoids into circulation)

Question 24

how are cells released from the marrow

Answer 24

-cytokines signal for increased release of cells
-in some cases cells are released before they are mature, for example:
‒ Immature neutrophils in infections
‒ Immature red blood cells in severe anemia

Question 25

on a PBS at 10x what do you check the tail for

Answer 25

platelet clumps and/or fibrin
edges for excess white cells
RBC arrangement
parasites and microfilariae,

Question 26

Platelet clumping present in smear

Answer 26

can be due to incorrect venipuncture technique
cells abnormal response to EDTA
platelet satellitism – where platelets surround the neutrophils

Microclots or fibrin strands present in smear which can trap PLTs and WBCs and falsely decrease their estimates and counts.

reject sample

Smudge cells – Should be included in the WBC estimate if they appear in large numbers –

Question 27

Performing the differential too deep into the thick area

Answer 27

WBC are distorted and could be misidentified.