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Leukocytes (WBC)
only formed element that is complete cell with nuclei and organelles
Normal Range for Leukocytes
4800 to 10800 per blood (5 to 11k)
Diapedisis
The process by which white blood cells can leave capillaries
Leukocytes move through tissue spaces by
ameboid motion and positive chemotaxis
positive chemotaxis
guides WBCs to invading pathogens, damaged tissues, how they find where they need to go
"chemical roadmap"
Leukocytosis
WBC count over 11,000/mm3
-Normal response to infection
2 major categories of leukocytes
granulocytes and agranulocytes
Granulocytes
contain visible cytoplasmic granules (neutrophils, eosinophils, basophils)
-larger and short lived than RBCs and all are phagocytic to some degree
Agranulocytes
do not contain visible cytoplasmic granules (lymphocytes, monocytes)
Mnemonic to remember decreasing abundance in blood
Never Let Monkeys Eat Bananas
-Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Neutrophils
Most numerous WBCs, w/ granules that stain with both acid and basic dyes containing either hydrolytic enzymes or antibacterial proteins
-3-6 lobes
Another name for neutrophils
polymorphonuclear leukocytes (PMNs) because nucleus is lobular
Function of Neutophils
phagocytosis referred to as "bacteria slayers" killing microbes by the process called respiratory burst
Respiratory burst (neutrophils)
cell synthesizes potent oxidizing substances (bleach or hydrogen peroxide)
Defensin granules (neutrophil) merge with __________________.
phagosome to form spears that pierce holes in the membrane of ingested microbe
Eosinophils
Red-staining granules that contain digestive enzymes that are released on large parasitic worms, digesting their surface
- also playing a role in allergies and asthma
Eosinophils physical characteristics
nucleus has 2 lobes connected by a broad band of DNA
Basohils
rarest WBC with large, purplish black granules that contain histamine
Histamine
inflammatory chemical that acts as a vasodilator and attracts other WBCs to inflamed sites
Lymphocytes
white blood cells crucial to immunity, found in lymphoid tissue (ex. lymph nodes, spleen), but a few circulate in blood
Lymphocytes physical characteristics
Large, dark purple, circular nuclei with thin rim of blue cytoplasm, about the same size as RBC
T lymphocytes (T cells)
act against virus-infected cells and tumor cells (many different ones)
B lymphocytes (B cells)
give rise to plasma cells (and B memory cells), which produce antibodies
Monocytes
white blood cells that leave circulation, enter tissues, and differentiate into macrophages
Monocytes physical characteristics
largest of all leukocytes, w/ an abundant pale blue cytoplasm that has U or kidney shaped nuclei
Macrophages
Actively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infections
Leukopoiesis
production of white blood cells, stimulated by chemical messengers from the red bone marrow and mature WBCs
Two chemical messengers used in leukopoiesis?
Interleukins (numbered) & Colony stimulating factors (CSFs) (named for WBC type they stimulate)
-signaling the pathway the cells will enter for production
All leukocytes originate from
hemocytoblast stem cells
2 branches of the hemocytoblast stem cell for leukocytes
Lymphoid stem cells
Myeloid stem cells
lymphoid stem cells
produce lymphocytes
myeloid stem cells
produce all other elements except lymphocytes
Right before mature granulocytes the cells are
Band cells, forming a curved arc
Mature granulocyte
nuclei become segmented before being released in blood
are there more WBCs formed or RBCs?
there are 3x more WBCs formed than RBCs, because WBCs have a shorter life, cut short by fighting microbes
Monocytes are derived from
myeloid line, and some mature into macrophages that reside in tissues and engulf pathogens
-can live several months
Monocyte production order
monoblast to promonocyte to monocyte
Lymphocytes are derived from
lymphoid line
-live from a few hours to decades
T lymphocyte precursors
give rise to immature T lymphocytes that mature in thymus
B lymphocyte precursors
give rise to immature b lymphocytes that mature within bone marrow
Platelet
fragments of larger megakaryocyte
-not a cell only fragments of a cell
chemicals involved in clotting process
Serotonin, calcium, enzymes, ADP, platelet-derived growth factor
function of platelets
form temporary platelet plug that helps seal breaks in blood vessels
Circulating platelets are kept inactive and mobile by
nitric oxide (NO) and prostacyclin from endothelial cells lining blood vessels so we don't randomly form blood clots
Platelet formation is regulated by:
Thrombopoietin (TPO)
Platelets are formed in myeloid line from
megakaryoblast (stage I megakaryocyte)
What happens during platelet formation?
mitosis occurs but no cytokinesis, resulting in large stage 4 cell with multilobed nucleus that will cause projections to break off into platelet fragments
Normal range for platelets
150,000-400,000/ml of blood
Hemostasis
fast series of reactions for stoppage of bleeding; requires clotting factors and substances released by platelets and injured tissues
3 steps involves involved in hemostasis
Step 1: Vascular Spasm
Step 2: Platelet plug formation
Step 3: Coagulation (blood clotting)
Vascular spasm
Vessel responds to injury with vasoconstriction, can significantly reduce blood flow until other mechanisms an kick in
-most effective in smaller blood vessels
vascular spasms are triggered by
-Direct injury to vascular smooth muscle (break in vessel)
-Chemicals released by endothelial cells and platelets
-Pain reflexes
platelet plug formation
Platelets stick to collagen fibers that are exposed when vessel is damaged, the do not stick to intact vessel walls because collagen is not exposed
-could have a successful stoppage of blood at this step for small vessel tears but larger breaks need additional step
prostacyclins and nitric oxide
secreted by endothelial cells act to prevent platelet sticking
von Willebrand factor
helps to stabilize platelet-collagen adhesion when you have a break
When platelet plug formation is activated, platelets
swell, become spiked and sticky, and release chemical messengers
Chemical messengers released by platelets during platelet plug formation
ADP, Serotonin, and Thromboxane A2
ADP (adenosine diphosphate)
causes more platelets to stick and release their contents
serotonin and thromboxane A2
enhance vascular spasm and platelet aggregation (clumping or clustering)
What kind of cycle is the platelet plug formation?
positive feedback cycle, as more platelets stick, the release more chemicals which causes more platelets to stick and release more chemicals
Coagulation
blood clotting that reinforces platelet plug with fibrin threads that form a mesh that traps red blood cells and platelets
-effective for dealing larger vessel breaks
Procoagulants
clotting factors used in coagulation, mostly plasma proteins
Clotting factors are numbered in
oder of discovery, 1-13
What is needed to synthesize 4 of the clotting factors
Vitamin K
Phase 1 of coagulation
initiated by two pathways (intrinsic or extrinsic) to prothrombin activator, triggered by tissue damaging events ending with the activation of factor 10, involving a series of procoagulants
Factor 10 then complexes with calcium, PF3 (platelet factor 3) and factor 5 to form
prothrombin activator
Intrinsic pathway of coagulation
clotting factors are present within the blood that is activated by exposed collagen
-triggered by negatively charged surfaces such as activated platelets, collagen, or even glass of a test tube
extrinsic pathway of coagulation
factors needed for clotting are located outside blood
-faster pathway because it bypasses several steps
extrinsic pathway of coagulation is triggered by
tissue cell trauma exposes the blood to Tissue Factor (factor 3)
Prothrombin activator converts (phase 2 of coagulation)
prothrombin (inactive) to active enzyme thrombin
Thrombin
converts inactive fibrinogen to active fibrin
Fibrin
Protein strands that form the basis of a blood clot, causing plasma to become a gel like trap catching formed elements
Thrombin (along with Ca2+) activates
what chemical is important in blood clotting?
calcium
Where are majority of blood clotting factors located?
liver, so if you have liver issues your susceptible to bleeding
when damage has been repaired clot must be
stabilized and removed
clot retraction
contraction of actin and myosin platelets pulls on fibrin strands squeezing serum from clot drawing ruptured blood vessel edges together
-vessel is healing even as clot retraction occurs
Serum
plasma minus clotting proteins
Platelet-derived growth factor (PDGF)
stimulates division of smooth muscle cells and fibroblasts to rebuild blood vessel wall
-released by platelets
Vascular endothelial growth factor (VEGF)
stimulates endothelial cells to multiply and restore endothelial lining
Fibrinolysis
Process whereby clots are removed after repair is completed
-breakdown of fibrin
Plasminogen
a inactive plasma protein that is trapped in clot and converted to plasmin
Plasmin
an active fibrin-digesting enzyme
tissue plasminogen activator (tPA)
Factor XII and thrombin all play a role in conversion process of converting plasminogen to plasmin
-"clot buster"- given in stroke patients
cardiovascular system minimizes effects of blood loss by
1. reducing volume of affected blood vessels (vasoconstriction)
2. stepping up production of RBCs
-but can only compensate for so much
Loss of 15-30% of blood causes
pallor and weakness
loss of more than 30% of blood results in
potentially fatal severe shock
Low blood volume may result in
death from shock
When there's low blood volume, that volume must be replaced immediately with
Normal saline (salt lev. in body fluid) or multiple electrolyte solution (Ringers Solution) that mimics plasma electrolyte composition
Infusions of Packed Red Blood Cells (PRBCs)
(plasma and WBCs removed), are preferred to restore oxygen-carrying capacity
shelf life of blood is about...
35 days
blood typing
-Donor blood is mixed with antibodies against common agglutinogens (antigens)
-If agglutinogen (antigen) is present, clumping of RBCs will occur
-Blood is typed for ABO and for Rh factor in same manner
Antigens
anything perceived as foreign that can generate an immune response
Agglutinogens
Antigens formed on the surface of red blood cells that promote agglutination (clumping) if mismatched blood is transfused
Mismatched transfused blood
perceived as foreign and may be agglutinated and destroyed (potentially fatal reaction)
Antigens of ABO and Rh blood groups cause
most vigorous transfusion reactions, therefore they are major groups typed
Anti-A or anti-B antibodies
act against transfused RBCs with ABO not present of recipients RBCs
-preformed
universal recipient
Type AB: no anti-A or anti-B antibodies
universal donor
Type O: no A or B antigens
Rh+ indicates presence of
D antigen