7 - WBC's and Platelets
LEUKOCYTES (WBC’S)
• Leukocytes, or white blood cells (WBCs), are the only formed elements that are complete cells. WBCs make up less than 1% of total blood volume.
• Leukocytes are critical to our defense against infection.
They can leave the blood to enter the tissues, a process called diapedesis. Once outside of the blood vessel, they move through tissues by amoeboid movement in extracellular fluids. Normally, only about 2% of the body’s total WBCs are circulating in the blood at any given time.
FUNCTIONS OF LEUKOCYTES
• Damaged cells release inflammatory signalling molecules. Leukocytes follow this trail of signal molecules to find the infection or tissue damage.
• Leukocytosis, an elevated white blood cell count
This indicates infection. Different types of white blood cell are activated by different types of infection, so a differential white blood cell count (comparing the numbers of each WBC type) can identify what type of infection the body is fighting.
• Leukopenia is a decreased white blood cell count — due to WBCs probably leaving the blood stream to fight infection elsewhere
• Granulocytes are a major group of leukocytes characterized as large cells with lobed nuclei and cytoplasmic granules that are visible when the cells are stained. The granules are secretory vesicles containing a mixture of cytotoxic molecules, such as enzymes and antimicrobial peptides. These cells are also known as polymorphonuclear cells (PMNs).
• Agranulocytes are lymphocytes and monocytes that lack cytoplasmic granules. They are also known as peripheral blood mononuclear cells (PBMCs)
GRANULOCYTES: neutrophils
• Neutrophils — 60-70% of all leukocytes, are chemically attracted to sites of inflammation and are active phagocytes.
• An increased neutrophil count can be caused by many things but is most commonly indicative of a bacterial infection. They are the most common white blood cell in pus
GRANULOCYTES: eosinophils
• Eosinophils are 2-4% of leukocytes. They attack parasites in the gut and connective tissues, and have a role in asthma and allergies.
• Eosinophils are effective against multicellular endoparasites such as worms. They can also help fight some respiratory viral infections (influenza/flu, RSV, etc.)
*In North America, they are commonly linked to allergic reactions, especially rashes
GRANULOCYTES: basophils
• Basophils are the least numerous/rarest type of leukocyte, 0.5-1% of all white blood cells, and release histamine to promote inflammation.
• Basophils are also associated with multicellular exoparasites such as ticks. In North America, they are commonly linked to allergies, especially for reactions involving coughing, sneezing and runny nose
AGRANULOCYTES: lymphocytes
•Lymphocytes, are 20-25% of white blood cells and are found throughout the body. They are the basis for the adaptive immune response.
Innate vs adaptive immune response:
Innate — always good to go — constantly looking for the same danger signs
— can start working quickly — but can’t learn to do its job any better
Adaptive — learns what might infect us, as our body undergoes new stuff
— then helps us to prepare for the next time we encounter that thing
**Vaccines — work by activating our adaptive immune response through these lymphocytes — takes abt 2-4 weeks for AIS to get good at recognizing + destroying something
• T lymphocytes directly attack virus- infected cells and tumour cells.
• B lymphocytes bind antigens and produce antibodies as plasma cells.
• Natural killer (NK) cells have a similar function to T cells but are part of the innate immune response
AGRANULOCYTES: monocytes
• Monocytes are 3–8% of white blood cells, become actively phagocytotic macrophages as they enter tissues, and can activate lymphocytes.
• Monocytes are common in chronic infections and inflammatory autoimmune diseases
LEUKOPOIESIS
Leukopoiesis, the formation of white blood cells, is regulated by chemical messengers such as interleukins and colony-stimulating factors.
• Leukopoiesis involves hematopoietic stem cells differentiating through one of two pathways:
-Lymphoid stem cells develop into lymphocytes.
-Myeloid stem cells develop into all other white blood cells, as well as platelets and RBCs.
• Band cells are immature granulocytes, like reticulocytes are immature erythrocytes
LEUKOCYTE DISORDERS
• Leukopenia is an abnormally low white blood cell count, sometimes caused by some medications, anticancer drugs or radiation, or some infections.
• Leukemias are cancers in which clones of a single white blood cell remain unspecialized and divide out of control. An indicator of leukemia can be an abnormally high number one type of band cells.
*Leukemia inspired the use of chemotherapy for cancer treatment
• Infectious mononucleosis (better known as mono) — is a disease caused by Epstein-Barr virus, characterized by excessive numbers of agranulocytes
*b cells that swell up and look funny, appearing like monocytes
PLATELETS
• Platelets are not complete cells, but fragments of bone marrow cells called megakaryocytes. A single megakaryocyte can produce 2,000-5,000 platelets. Platelets have a lifespan of approximately 10 days
PLATELET FUNCTION
• Platelets are critical to the clotting process, forming the temporary seal when a blood vessel breaks.
• Thrombopoietin is a hormone that regulates the formation of platelets (thrombocytes), which takes place by repeated mitoses of megakaryocytes without cytokinesis.
• Platelets enter the blood when a megakaryocyte sends cytoplasmic extensions through a blood vessel wall, ruptures and releases platelets
HEMOSTASIS
**how we clot blood. to limit blood loss after an injury
Three steps occur:
1. Vascular spasm
2. Platelet plug formation
3. Coagulation (clotting)
*there are also three stages to coagulation
1 - Vascular spasms
Vascular spasms are the immediate vaso-constriction response to blood vessel injury and become more efficient with increased tissue damage.
• They are a temporary mechanism to reduce blood flow until other mechanisms can begin
2 - Platelet plug formation
• When endothelium is damaged, platelets will stick to exposed collagen fibres to form a platelet plug.
• When the vessel walls are intact, there is no exposed collagen for the platelets to stick to and endothelial secretions prevent platelet sticking.
When activated, platelets swell, becoming spiked and sticky, adhering to each other and the damaged blood vessel wall. Once attached, other platelets are attracted to the site of injury, activating a positive feedback loop for clot formation.
3 - Coagulation
• Blood clotting or coagulation is a multistep process in which blood is transformed from a liquid to a gel
• Coagulation reinforces platelet plugs with fibrin threads to seal larger vessel breaks.
• Factors that promote clotting are called clotting factors, or procoagulants. Factors that inhibit clot formation are called anticoagulants
3 stages of the clotting process:
1. The formation of prothrombin activator through
either the intrinsic pathway or extrinsic pathway.
2. The prothrombin activator from either the intrinsic
or extrinsic pathway catalyzes the transformation
of prothrombin into the active enzyme thrombin.
3. Thrombin converts soluble fibrinogen into
insoluble fibrin. Fibrin causes plasma to become a
gel-like trap to catch formed elements. Thrombin
also activates fibrin stabilizing factor to cross-link
fibrin into a strong mesh to stabilize the clot
PATHWAYS FOR PROTHROMBIN ACTIVATION
Two pathways can form prothrombin activator:
• The intrinsic pathway, so named because all factors necessary are present within the blood, can clot blood when the inside of the blood vessel is rough or damaged, and blood flow is slow.
• The extrinsic pathway is triggered when tissue factor leaks into the blood from outside the blood vessel walls. This clotting cascade can occur rapidly by bypassing some of the intrinsic pathway steps, and is more important for clotting blood
FIBRIN MESH
Thrombin catalyzes the reactions that convert fibrinogen to fibrin, which produces strands that form the structure of a clot
CLOT RETRACTION AND FIBRINOLYSIS
• Clot retraction is a process in which the contractile proteins (myosin and actin) within platelets contract and pull on neighboring fibrin strands, squeezing plasma from the clot and pulling damaged tissue edges together. This typically occurs within 30-60 minutes.
• Repair is stimulated by platelet-derived growth factor to stimulate endothelial cell division.
• Fibrinolysis removes unneeded clots through the action of a fibrin-digesting enzyme called plasmin
FACTORS LIMITING CLOT FORMATION
Two mechanisms limit the size of clots as they form:
1.
Rapidly moving blood disseminates clotting factors before they can initiate a clotting cascade.
2.
Activated clotting factors are inhibited by other compounds in the blood. For clotting to occur, the concentration of activated clotting factors must overcome a minimum concentration.
• As long as the vascular endothelium is intact, and
blood is flowing smoothly, clotting should not occur