Case 1
Blood composition
Blood contains three layers:
1. a red layer that contains the erythrocytes
2. a buffy coat, which is a thin, whitish layer that
contains the leukocytes and the platelets
3. plasma, that contains different solutes (nutrients,
gases, hormones, wastes), plasma proteins
(albumin, globulin, fibrinogen) and electrolytes
- serum is plasma but without the
coagulation factors and fibrin
Blood contains three formed elements:
1. erythrocytes = red blood cells
2. leukocytes = white blood cells
3. thrombocytes = platelets
Erythrocytes
Erythrocytes structure
Erythrocytes are biconcave discs that lack a nucleus and organelles. Spectrin maintains the
biconcave shape of the RBC so they can fit through capillaries. They contain antioxidant
enzymes and structural proteins for the deformation. The most profound protein is
hemoglobin. The RBCs are produced (erythropoiesis) in the bone marrow and broken down
by the liver.
Erythrocytes function
RBC transport respiratory gases. Three structural characteristics contribute to gas
exchange:
1. small size and biconcave shape that increases the surface area
2. having less water content sol there is more space for hemoglobin
3. lacking mitochondria and getting energy by anaerobic mechanisms so they don’t use
oxygen
Structure hemoglobin
Hemoglobin consists of one heme pigment, which binds iron, and the protein globin that
consists of four polypeptide chains (2α, 2β). It consists in three forms:
1. oxyhemoglobin= when it is oxygenated (bright red)
2. deoxyhemoglobin= when it is reduced (dark red)
3. carbaminohemoglobin= when oxygen is reduced and carbon dioxide binds
Disorders
- anemia= the oxygen-carrying capacity is too low.
- sickle cell anemia= when the RBCs look like a C. A symptom is hypoxia.
,Thrombocytes
Platelets are cell fragments of 2-3 µm of megakaryocytes (mega cells). They are formed by
thrombopoietin. The megakaryocyte has repeated mitosis but without cytokinesis so they
become a megakaryoblasts which ruptures. They can very quickly respond to triggers and
change their shape. They have granules that contain clotting chemicals (Ca2+, enzymes,
serotonin, ADP, platelet derived growth factor (PDGF)). They die within 10 days if they are
not involved in clotting. Not all the platelets have the same function (signaling, aggregating,
supporting, procoagulant producing).
Leukocytes
WBCs are the only formed elements that are actual cells. They are produced in the bone
marrow. They use:
1. diapedesis = slipping out of the capillary system
2. amoeboid motion= forming cytoplasmic extensions for moving
3. positive chemotaxis= following the cytokines
Granulocytes
Granulocytes are the neutrophils, eosinophils and basophils. They are spherical in shape,
have lobed nuclei, have membrane bound cytoplasmic granules and are involved in
phagocytosis.
1. Neutrophils: they are the first leukocyte to arrive at the site of inflammation. Their
nucleus is lobed and can either be segmented or not. Their granules are hydrolytic
enzymes (lysosomes) or antimicrobial proteins (defensins). The myeloid stem cell is
the precursor.
- function: they phagocytose bacteria and fungi by forming phagolysosomes
mediated by defensins.
2. eosinophils: they have a nucleus that resembles a telephone. Their granules are
lysosomes filled with digestive enzymes. They are located in the connective tissues
close to the respiratory/intestinal mucosa. The myeloid stem cell is the precursor.
- function: they do not digest bacteria but attack parasites/helminths that are
too large to be phagocytosed.
, 3. basophils: they are the rarest leukocyte. The nucleus has a U/S shape. Their
cytoplasm contains large, coarse, histamine-containing granules. The myeloid stem
cell is the precursor.
- function: they release histamine which acts as a vasodilator and attracts other
WBCs to the inflamed site.
Agranulocytes
The agranulocytes are the lymphocytes and the monocytes. They lack visible cytoplasmic
granules. Their nuclei are spherical or kidney shaped.
1. Lymphocytes: they are associated with the lymphoid tissues (lymph nodes, spleen,
MALT). They have a large nucleus that occupies most of the cell volume. The
lymphoid stem cell is the precursor.
a. T-lymphocytes: function in immune response by directly acting against
virus-infected cells and tumor cells
b. B-lymphocytes: give rise to plasma cells, which produce antibodies
(immunoglobulins) that are released to the blood
2. Monocytes: they are the largest leukocyte. They differentiate into macrophages. The
myeloid stem cell is the precursor.
- function: macrophages phagocytose pathogens and activate lymphocytes (as
APC).
Never Let Monkeys Eat Bananas → most numerous to less numerous
Recruitment of leukocytes
1. rolling: E-selectin is activated by the endothelial lining of the capillary
2. adhesion: The leukocyte releases a glycoprotein, S-Lex, which binds to E-selectin in
order to slow down the rolling process. Then the leukocyte expresses the integrin
, LFA1, which interacts with ICAM-1 and VLA-4, which interacts with VCAM-1 on the
surface of the endothelium, so the leukocyte holds
3. crawling: The leukocyte undergoes cytoskeletal rearrangements
4. transmigration/diapedesis: the leukocyte goes through the gaps of the capillary wall
5. chemotaxis: chemokines attract the leukocyte and allow it to migrate along its
gradient, so the leukocyte is at the site of inflammation
Hemostasis
Hemostasis is a process that stops bleeding from a blood vessel by forming a plug. The
hemostasis response is fast (within minutes), localized and carefully controlled.
Primary hemostasis
Vascular spasm
During vascular spasm, the smooth muscle in the walls of the vessel contracts
(vasoconstriction) to reduce the blood flow and bleeding at the site of injury. This is triggered
by chemicals, called endothelins, that are released by vessel-lining cells and by pain
receptors.
Platelet plug formation
Then in the second step platelets
encounter the vessel rupture with
underlying connective tissue and
collagenous fibers. Then they
become sticky and begin to bind
to the underlying collagen until
the platelet plug is formed. This
process is called platelet
aggregation and it is assisted by
a plasma protein called von
Willebrand factor on the vessel
wall. This protein stabilizes the
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