Haemostasis

Question 1

White blood cells (WBCs)

Answer 1

Role: stimulating immune responses of the body and controlling inflammation
* need to leave capillaries/circulation and then act on different tissues where there’s a particular immune threat that needs to be eliminated.

5 types located in the blood
* neutrophils
* eosinophils
* basophils
* monocytes
* lymphocyte

Question 2

Explain the characteristics of each white blood cell that allow them to be identified under a light microscope

Answer 2

• Usually identified by staining and by the size and shape of their nucleus, their cytoplasmic contents and cell border

1. neutrophil
   * very easy to spot
   * a multilobular nuclei
   * 3-5 lobes to the nucleus
2. eosinophils
   * bilobular structure of their nuclei (2 lobes)
3. basinophils
   * similar structure to eosinophils with 2 lobes but difficult to see it
   * granules in cytoplasm also positively stain and cover up nuclei

basino/eosino/neutrophils = granulocytes (contain granules within cytoplasm)
–> release these Granules, from their cytoplasm, which contain a
lot of cytotoxic components to help eliminate that that immune threat.

4. monocytes
   * Well defined nuclei
   * only one lobe and nice cytoplasm
5. lymphocytes
   * similar to monocytes
   * very little cytoplasm

mono/lymphocytes = agranulocytes (does not contain granules in cytoplasm)

Question 3

5 types of WBC located in the blood

Answer 3

• neutrophils
• eosinophils
• basophils
• monocytes
• lymphocyte

Question 4

neutrophils

Answer 4

• Most numerous WBC (50-70%) but have a very short life span (1-2 days)

Appearance :
Easily identified by 3-5 lobular segments of nucleus

Mechanism :
1st responder to any bacterial infection
Phagocytic by ingestion of bacteria
* Release variety of cytokines from granules
- primary substance released being Pyrogens ie. fever-causing substance

role of pyrogens
1. elevate the temperature of
the body so that these immune cells can work more
effectively
2. raising the temperature so bacteria can no longer replicate and cause the damage that they’re doing to whatever organ they’ve infected.

Question 5

Eosinophils

Answer 5

• Small population (1-3%) of WBCs but are easily identified by pink-staining granules in the cytoplasm
  = eosinophils become much more elevated compared to other cells with allergic reactions and parasitic diseases
• Classified as a cytotoxic cell type as they kill pathogens
• Attach and release substances from the granules that damage or kill

Question 6

Basophils

Answer 6

• Very rare (~1% of WBCs) but easily identified by large, dark blue granules in the cytoplasm
• Play a role in parasitic infections and allergies.
  called basophils because they respond to a basic pH state
• Release mediators that contribute to inflammation
  during immune response
• Histamine
• Heparin : prevent clotting from happening and allow inflammation to infiltrate the tissue that needs help (when the endothelial layers become permeable for the immune cells to respond but make blood vessels prone to clotting since other molecules can also enter capillaries now)
• Other cytokines
  ==> which work in concert to exacerbate and sustain inflammation

Question 7

Monocytes

Answer 7

• Precursors of macrophages and are not very common (1-6% of total WBCs)
• Kidney bean-shaped nucleus
• Mature and enlarge in tissue
• Life span can range from several months to years
• Become professional phagocytes
• Macrophages = “large eaters” / second line of defense when neutrophils can’t phagocytose a certain macrophage

Question 8

Lymphocytes

Answer 8

• Key cells that mediate the acquired immune response of the body that make up 20-30% of WBCs
• Lymphoid precusor differentiates into 3 subtypes:
• B lymphocytes : make the antibodies
• T lymophocytes : deal with viral pathogens, and consists of cytotoxic cells as well.
• Natural Killer cells (NK cells) : responsible for protecting yourself
  against viral invaders
• Important in protecting against viruses

Question 9

lymphoma

Answer 9

cancer down the pathway of stemcell -> lymphocyte stem cell –> lymphocyte
1) Hodgkins
–> unlike the Non hodgkins, not a cancer of those three cells, but of a new, different type of cell that arises from a beta cell or from a B lymphocyte ( dont need to know this but Reed sternberger cells.)
2) Non hodgkins (more dominant lymphoma)
–> it is cancer of those three cell types: natural killer cells, your B and your T lymphocytes,

Question 10

leukemia

Answer 10

• Acute myelogenous leukemia (AML)
• Acute lymphocytic leukemia (ALL)
  different cytokines (colony stimulating factors/ interleukins)
• Chronic myelogenous leukemia (CML)
• Chronic lymphocytic leukemia (CLL)

acute / chronic
=> acute leukaemia affect the more immature cells within blood celll production (more aggressive)
–> more aggressive because they are more sensitive to all those
=> chronic affect the more mature cell phenotypes down here.

myelogenous/ lymphocytic
lymphocytic :
–> are the ones that have to do with your lymphoid progenitor cells
–> the ones that lead to the lymphocytes of phenotypes.
myelogenous:
–> lead to all the other different cell types that arise from the myeloid stem cell e.g red blood cells, your platelets,
and also these four different phenotypes of white blood cells.

Question 11

Myelodysplastic syndromes (MDS)

Answer 11

the production of abnormal myeloid cells
=> cells that arise from this myeloid progenitor
== producing these sort of abnormal, mature phenotypes

dysplasia = abnormal

Question 12

Neutropenia

Answer 12

you’ve got a deficiency in your neutrophils == susceptible to things like bacterial infections.
penia = deficiency

Question 13

Platelets

Answer 13

• Cell fragments produced in the bone marrow from Megakaryocytes
• Small and colourless with no nucleus
• unlike RBC, contain mitochondria, smooth ER and vesicles filled with cytokines and other factors
• Always present in blood and have a life span of ~10 days
• Role in haemostasis (clotting)

Question 14

Haemostasis

Answer 14

haemostasis takes place during bleeding to limit the amount of blood that you lose when your blood system or your blood supply ends up becoming physically compromised

• 3 major steps:
• Vasoconstriction
• Formation of platelet plug
• Coagulation

Process of keeping blood within a damaged blood vessel

Question 15

Haemostasis I (first step)

Answer 15

Vasoconstriction
= blood vessels that are supplying
that blood, they constrict
- Decreases blood flow and pressure in the vessel temporarily

==> Caused by paracrine molecules from the endothelium
detect that blood is being lost, they’ll then secrete factors into your smooth muscle layer, which is the layer that exists within your vessel wall that causes that blood vessel to constrict and again limiting the amount of blood flow to that area.

Question 16

Haemostasis II

Answer 16

1. endothelial cell layer is compromised and exposed collagen in damaged blood vessel wall activates the platelets
2. release of platelet factors
3. factors attract more platelets to accumulate at the injury, positive feedback loop
4. platelets aggregate into platelet plug

endothelial cells make sure blood flow smoothly by releasing prostacyclin and nitric oxide to prevent platelets from adhering

Question 17

Haemostasis III

Answer 17

• 3. Coagulation
• Formation of a clot
• Divided into two pathways: Intrinsic and Extrinsic
• At each step, an enzyme converts an inactive precursor into an active enzyme
• Driven by Ca2+ (mostly)
• Coagulation is an interactive process rather than a cascade of events

intrinsic pathway :
* damage to endothelium, exposure of collagen, factors located inside blood vessel

Question 18

Intrinsic pathway

Answer 18

1. collagen and other factors that stimulate this this pathway.
   –> leads to the activation of factor 12.
2. Factor 12 with Ca2+ leads to the activation of factor 11
3. this then leads to the activation of factor 9
   –> this is where the intrinsic and extrinsic pathways begin to meet

Question 19

common pathway

Answer 19

1. extrinsic and intrinsic pathways meet
2. activates factor 9 together with factor 8.
3. this then activate factor 10
4. factor 10 activates the conversion of prothrombin into its active form known as thrombin (use of Ca2+)
5. thrombrin is an active enzyme that converts fibrinogen –> fibrin// also activates factor 13
6. fibrin goes on with the help of Ca2+ and factor 13 to form crosslinked fibrin

Question 20

Clot retraction and dissolution

Answer 20

if clot is not broken down and flows downstream up to your heart/brain = heart attacks or strokes

fibrinolysis prevents this from happening : retraction/dissolving of the clot

1. thrombin is used to convert plasminogen into its active form plasmin with tissue plasminogen activator or TPA.
2. plasmin works by chopping up all of these fibre networks, cleaving off fibrin polymers ==> into smaller fragments
3. smaller fragments easier to dissolve clop

Question 21

Disorders of the coagulation pathway

Answer 21

Best known: Haemophilia == Often inherited
features : Bruise easily and may be prone to internal bleeding

• deficiency in one of the factors in the coagulation cascade
• Haemophilia A, B and C.
  e.g. A is the most common (80% of cases) ==> deficiency of Factor VIII

Question 22

One of the initial steps of the common coagulation pathway is the:
A) Sticking of platelets to damaged tissue
B) Release of tissue factor
C) Activation of a clotting factor that converts prothrombin to thrombin
D) Activation of a clotting factor that converts fibrinogen to fibrin

Answer 22

A) Sticking of platelets to damaged tissue
B) Release of tissue factor
C) Activation of a clotting factor that converts prothrombin to thrombin
D) Activation of a clotting factor that converts fibrinogen to fibrin

A = initiaation of platelet plug
B = start of extrinsic pathway
D = end of common pathway

Question 23

extrinsic pathway

Answer 23

1. damage expose tissue factor/ factor 3
2. factor 3 activates factor 7
3. factor 3&7 with factor 11 from intrinsic pathway activate factor 9
   ==> start of common pathway