Blood Flashcards
Blood
Functions:
- Transport
- Gases ( e.g., O2, CO2)
- Nutrients and waste products
- Regulatory molecules (e.g., hormones)
- Homeostasis
- Thermoregulation
- Protection
- Vascular integrity (e.g. coagulation)
- Immune cells and molecules (e.g., IgGs)
Blood volume
approximately 6 liters or 7-8% of body weight.
O2 and CO2 are transported in blood via different mechanisms
Plasma
Top layer of separated blood components
Plasma at the top containing albumin, fibrinogen, immunoglobulin’s, lipids (lipoproteins), hormones, vitamins and salts as predominant components.
The middle layer of separated components in blood
WBCs & platelets
A Buffy coat of leukocytes (WBC) and platelets (1%)
Bottom layer of separated components of blood
A bottom layer of RBC 43-47% which is the hematocrit
How do you separated blood into three seperated components?
Centrifugation with Anticoagulant
What happens to blood without anticoagulant added?
Blood will clot and blood cells will get caught in the clot leaving serum behind
A protein-rich fluid lacking fibrinogen but contains albumin, immunoglobulins and other components
Serum
Blood is made up of two components:
- Plasma
- Formed elements
Mostly water with dissolved substances:
Plasma
electrolytes, gases (O2, CO2), nutrients, waste products and regulatory molecules.
Plasma Proteins:
- Albumin – the most abundant protein (~65%), responsible for blood osmolarity and viscosity.
- Fibrinogens or clotting proteins - prothrombin, fibrinogen and others.
- Globulins - found as antibodies, as well as storage and transport proteins
- Some storage or transport proteins are made by other cells such as in the thyroid
- Antibodies are produced by lymphocytes
Formed elements component of blood
Blood cells and their derviatives - neutral strains
- Erythrocytes - red blood cells, carry hemoglobin and certain other substances, 5 to 6 x 106/mm3
- Leucocytes (also leukocytes) - white blood cells, part of defense and immune mechanisms, 5 to 10 x 103/mm3
- Thrombocytes - platelets, instrumental in the intrinsic blood clotting pathway, 150 to 200 x 103/mm3
RBCs constitute > _______ of blood cells by number
99%
Hematocrit -
packed RBC volume (% of blood volume)
Lifespan of blood components
- Neutrophils - only 12-14 hours (longer if activated)
- Platelets, ~10 days
- RBCs, ~ 4 months (~120 days)
- Lymphocytes, many years
Resilient and flexible shape of RBC is due to _________ based membrane skeleton linked to cytoplasmic side of the plasma membrane
spectrin
Erythrocytes are the most abundant cells of the body and contain ________ that carries O2 and carbon dioxide
hemoglobin
catalyses the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions).
Carbonic anhydrase
Aged RBC are phagocytosed by
macrophages in liver and spleen
An autosomal dominant disorder causes defects in the cytoskeleton due to defective self-association of spectrin subunits and binding of to ankyrin, protein 4.1 defects and glycoprorin
Elliptocytosis
hemoglobin genetic defects (α2 βS2) changing the biconcave disk shape of RBC into rigid less deformable sickle –shaped cells.
Sickle cell anemia
defective synthesis of α or β chains of the normal hemoglobin tetramer (α2 β2). Defined by anemia produced by the defective synthesis of the hemoglobin molecule and hemolysis
Thalassemia
characterized by larger than normal RBC’s.
Macrocytic anemia
Microcytic anemia is characterized by smaller than normal RBC’s
The last stage of RBC development
______ % are released into the blood
Reticulocytes
a small 1% are released into the blood
Leukocytes size -
larger than erythrocytes (10 - 18 micron diameter)
contain specife granules with specific enzymes for each cell type
granulocytes
All contain azurophilic granules (Primary granules) that are large lysosomes but also contain microbicidal agents (myeloperoxidase)
They also contain smaller Secondary granules that secrete inflammatory mediators during inflammation
Also small tertiary granules - secrete gelatinase also insert adhesion molecules into cell membranes to facilitate phagocytosis
Agranulocytes
no granules present
Leukocytes Differential Count
Granulocytes: Mult-lobed nucleus
Originate in the myeloid tissue in the red bone marrow
Leukocyte granules
Granules contain digestive enzymes and all granulocytes can act as phagocytes.
Primary (azurophilic) granules these are lysosomes. All three of the granulocytes have these
The most numerous WBC, about 65% of normal white count. Most important phagocytic cell in the circulation.
Neutrophils
Motile Neutrophils leave vessels and migrate to their site of action throughout the body,
Distribution-
Function-
Diapedesis-
Chemotaxis-
Distribution - blood and CT (as transient or wandering cells)
Function - immune protection, movement (cell motility)
Diapedesis - movement out of blood into connective tissue
Chemotaxis - movement directed by homing molecules
Constitute 2-5% of circulating leukocytes. Measure 12-17 microns in diameter and have a bilobed nucleus and are larger than neutrophils. Easily recognized by its large specific bright red eosin granules.
Eosinophils
The crystalloid core of the eosinophils granules is composed of ______________. During allergic reactions, these cells ________________by secreting an antihistamine (histaminase)
Major basic proteins (MBP); counteract the action of the basophils
The specific granules contain a crystalloid body (seen in TEM). The granules contain four major proteins:
- an arginine-rich protein, Major Basic Protein (MBP) localized in the crystalloid body accounting for the intense acidophilia of the granule.
- Other proteins : eosinophil cationic protein (ECP),
- eosinophil peroxidase (EPO)
- eosinophil- derived neurotoxin (EDN) are in the granule matrix
Specific granules also contain:
histaminase, arylsulfatase, colagenase, and cathepsins.
Azurophilic granules are
lysosomes
They contain the usual lysosomal acid hydrolases and other hydrolytic enzymes that destroy parasites and hydrolysis of antigen-antibody complexes engulfed by Eosinophils.
Eosinophils also play a role in
allergic reactions ,parasite infections, and chronic inflammation.
The intestinal wall contains larger numbers of Eosinophils than the blood stream
increased eosinophils in circulation
eosinophilia
Found in many types of parasitic disease in which there the number of circulating eosinophils is increased
Intestinal parasites is the main cause of Eosinophilia world-wide
In the U.S. eosinophilia is often due to asthma or allergies
measure 14-16 μm in diameter and are bilobed with numerous densely specific granules that are fewer and larger than those in Neutrophils.
constitute less than 1% of leukocytes, except during infections where they mediate inflammation by secreting histamine and heparan sulfate (related to the anticoagulant heparin ) and leukotrines.
_______ makes blood vessels permeable
______ inhibits blood clotting
_________are functionally related to mast cells
Histamine; heparin, basophils
The cytoplasmic granules of basophils and mast cells contain ______composed of sulphated glycosaminoglycans linked to a protein core= which accounts for their metachromatic staining property
proteoglycans
The proteoglycans are a mixture of heparin and chondroitin sulphate.
Basophils can modulate
the immune response of other immune cells
May serve a role in defense against certain intestinal parasites
Basophils rapidly infiltrate sites of inflammation in allergy and asthma
- Infiltrate bronchioles during asthmatic attack
- Infiltrate nasal passages in hay fever
- Infiltrate site of inflammation in other allergies
Basophils have receptors for IgE on their surface.
When cross-linked, inflammatory mediators are released which can damage normal tissues
Histamine and other substances released by activated mast cells and basophils are responsible for
the symptoms of allergies including hives, hay fever, and anaphylactic shock.
The agranulocytes “heavy hitters”
Lymphocytes and monocytes
Lymphocytes
- T cells
- B cells
- Natural killer (NK) cells
Produce immunoglobulins (antibodies)
B-Lymphocytes
Both ___ and ____ once activated form long-lived memory cells
B and T cells
•These are responsible for a more intense and faster immune response the second time an antigen is encountered
NK cells kill virus-infected and malignant (transformed) cells
circulate ½-4 d in the blood, then enter the connective tissue, where they become macrophages
Monocyte
•Because these cells are in the connective tissue, they serve as the residential defense against pathogens.
Phagocytic for bacteria, foreign matter and necrotic tissue
- Liver
- Lung
- Brain
- Bone
Macrophages
- Kupffer cells: Liver
- Dust cells: Lung
- Microglia: Brain
- Osteoclasts: Bone
Increased monocytes are seen in the blood in what conditions?
chronic inflammatory conditions and tuberculosis
monocytosis
are small cytoplasmic fragments (2-4 μm) derived from the megakaryocyte., under control of the glycoprotein ________produced in the kidney and liver.
Thromocytes (platelets)
thrompopoietin
Thrombocytes represent fragmented cells which contain _________
They are seen in peripheral blood either singly or, often, in clusters, and have a lifespan of __________
residual organelles including rough endoplasmic reticulum and Golgi apparati;
5-10 days
the “stopping of the blood”. Triggered by a ruptured vessel wall it occurs in several steps:
Hemostasis
When blood vessels are damaged, platelets bind to exposed subendothelium and are activated.
Substances released when platelets are activated include
- Platelet-derived growth factor (PDGF)
- Fibrinogen
- Serotonin
- ADP
TEM of Megakaryocyte showing ____________ in cytoplasm. Inset shows BS of Megakaryocyte
platelet demarcation channels
Platelets
- Cell fragment-
- Structure-
- Granules-
- Megakaryocyte-
- Function-
- Cell fragment - small (~2 µm), irregular disk shape, no nucleus
- Structure - granules, mitochondria, glycogen, cytoskeleton
- Granules - alpha (clotting factors), dense core (histamine)
- Megakaryocyte - produces platelets in bone marrow sinus
- Function - clot formation, bind to injured blood vessel wall, aggregate with RBCs forms hemostatic plug (stops bleeding)
Platelets number from
150,00-400-000/ ml in the circulation with a 5-10 day lifespan
The major functions of platelets include:
- Formation of plugs to occlude damaged vascular sites by adhering to collagenous tissue which is later replaced by fibrin.
- They promote clot formation by providing a surface to assemble coagulation protein complexes for thrombin generation.
- Platelets secrete factors involved in repair.
Hematopoiesis
Yolk sac phase-
Hepatic phase-
Bone marrow phase-
Adult phase -
- Yolk sac phase - blood in ‘islands’ in yolk sac, no leukocytes
- Hepatic phase - primitive nucleated RBCs, fetal hemoglobin
- Bone marrow phase - mature RBCs, leukocytes, ~12 weeks
- Adult phase - pelvis, vertebrae, skull, ribs, ends of long bones
Undifferentiated cell producing blood cells of all lineages are capable of self-renewal
Pluripotent hematopoietic* stem cell (HSC)-
Undifferentiated cell producing cells of multiple lineages, limited self-renewal (e.g., myeloid SC, lymphoid SC)
Multipotent HSC
undifferentiated cell capable of producing cells of one lineage, colony forming units (CFUs)
(e.g., erythroid CFU, granulocyte-macrophage CFU)
Committed progenitor
Hematopoietic Growth Factors
Erythropoietin (EPO) - major regulator of erythropoiesis, stimulates erythroid CFU cells and proerythroblasts
Thrombopoietin (TPO) - increases platelet production, stimulates megakaryocyte CFU cells
Granulocyte CSF (G-CSF) - increases production of neutrophils, stimulates granulocyte-macrophage CFU cells
Granulocyte-macrophage CSF (GM-CSF) - increases macrophage production, stimulates granulocyte-macrophage CFU cells
Interleukins - stimulate B- and T-cell formation, function together with G-CSF and GM-CSF
Bone Marrow
- Bone marrow cavity
- Bone marrow cells
- Blood vessels
- Stem cells
- Bone marrow cavity - marrow proper and venous sinuses
- Bone marrow cells - stromal cells, adipocytes, endothelial cells, macrophages, hematopoietic cells
- Blood vessels - nutrient arteries supply marrow cavity
- Stem cells and early precursor cells do not leave marrow
