Blood Flashcards
Conducting system
Blood vessels
Functions of cardiovascular system
■ To transport materials to and from cells:
■ oxygen and carbon dioxide
■ nutrients
■ hormones
■ immune system components
■ waste products
■ Maintain Homeostasis
🩸 Contains cells suspended in a fluid called…
Plasma
Tissue type
Connective tissue
5 functions of 🩸
• Transport of dissolved substances
• Regulation of pH and ions
• Restriction of fluid losses at injury sites
• Defense against toxins and pathogens
• Stabilization of body homeostasis
-regulation of pH, osmotic pressure, and temp (removes excess heat)
Plasma
-(more than 90% of plasma is) Water
- Dissolved plasma proteins
- Is similar to, and exchanges fluids with, interstitial fluid
- Is matrix of formed elements
-makes up 50-60% of blood volume
3 types of formed elements
1) Red blood cells (RBCs) or erythrocytes:
■ transport oxygen
2) White blood cells (WBCs) or leukocytes:
■ part of the immune system
3) Platelets:
■ cell fragments involved in clotting
Hemopoiesis/hematopoiesis
■ Process of producing formed elements
■ By myeloid and lymphoid stem cells
Characteristics of blood
■ 38°C (100.4°F) is normal temperature
■ High viscosity
■ Slightly alkaline pH (7.35–7.45)
Whole 🩸
plasma (55%) and formed elements (mostly RBCs (45%))
Serum
Plasma w/o its clotting capability (w/o fibrinogen and other clotting factors)
Interstitial fluid (IF)
same as plasma but with about 25% less protein; it is found in
the interstitium
Lymph
same as interstitial fluid except it is found in lymphatic vessels
🩸volume
■ Blood volume (liters) = 7% of body weight (kilograms):
■ adult male: 5 to 6 liters
■ adult female: 4 to 5 liters
3 classes of plasma proteins
■ Albumins (60%)
■ Globulins (35%)
■ Fibrinogen (4%)
Albumins
■ Are synthesized by the liver
■ Contribute to oncotic pressure
■ Have a buffering potential
■ Transport substances:
■ fatty acids
■ bilirubin
■ thyroid hormones
■ steroid hormones
Globulins
• Antibodies, also called immunoglobulins or Gamma Globulins
-Are synthesized by competent B lymphocyte plasma cells
• Transport globulins (small molecules):
-hormone-binding proteins
-metalloproteins
-apolipoproteins (lipoproteins)
-steroid-binding proteins
-Are synthesized by the liver
Fibrinogen
■ Molecules form clots (inactive clotting protein)
■ Produce long, insoluble strands of fibrin
■ Are synthesized by the liver
■ There are also small amounts of other clotting factor proteins
Serum
■ Liquid part of a blood sample:
■ in which dissolved fibrinogen has converted to solid fibrin
■ Remove fibrin and clotting factors
■ Ca2+ also removed
Solutes
■ Include:
■ Non-Protein Sources of Nitrogen (NPNs)
■ Nutrients
■ Electrolytes
Non-protein nitrogen sources (NPN)
-Include:
-Urea - a metabolic waste produced from deamination of amino acids
-Uric Acid - a metabolic waste produced from the catabolism of nucleic acids
-Creatinine - a metabolic end product of creatine and creatine phosphate
-excreted by kidneys
-kidney disease is often indicated by elevated NPNs
Nutrients
■ Include:
■ Monosaccharides - mainly glucose
■ Amino Acids
■ Fatty Acids
■ Lipoproteins (chylomicrons, HDL, LDL, IDL, VLDL)
■ Vitamins
Electrolytes
■ Include:
■ Na+ - major regulator of osmotic tone
■ Cl –
■ Ca 2+
■ Mg 2+
■ PO4 3-
■ SO4 2-
■ HCO3 –
■ K+
Measuring RBCs
■ Red blood cell count:
■ reports the number of RBCs in 1 microliter whole blood
■ Hematocrit (packed cell volume, PCV):
■ percentage of RBCs in centrifuged whole blood
■ Buffy coat – The thin layer of white blood cells and platelets above the packed RBCs
Normal 🩸 counts
■ RBC:
■ male: 4.5–6.3 million
■ female: 4.2–5.5 million
■ Hematocrit (%):
■ male: 40–54
■ female: 37–47
RBC
-Small and highly specialized disc
-Thin in middle and thicker at edge (biconcave)
Importance of RBC shape and size
-High surface-to-volume ratio:
-quickly absorbs and releases CO2
-Discs bend and flex entering small capillaries:
-7.8 µm RBC passes through 4 µm capillary
-Discs form stacks:
-smoothes flow through narrow blood vessels
Why is there no nucleus or mitochondria in RBCs?
The nucleus is also not required as a mature RBC does not divide.
Mitochondria is absent so that oxygen is not utilised by the RBC and all the oxygen is transported to target areas
Lifespan of RBCs
■ Lack nuclei, mitochondria, other organelles
■ Suffer wear and tear in the cardiovascular system
■ Live about 120 days
Hemoglobin (Hb)
■ Protein molecule, transports respiratory gases
■ Normal hemoglobin (adult male):
■ 14–18 g/dl whole blood
Hemoglobin structure
■ ______________ quaternary structure
■ 4 globular protein subunits (each similar to myoglobin) :
■ 2 alpha chains and 2 beta chains globular
■ These globular subunits are what binds CO2
■ each with 1 molecule of heme
■ each heme contains 1 iron ion which can bind 1 O2 molecule
■ Iron ions easily:
■ associate with oxygen (oxyhemoglobin)
■ or dissociate from iron compounds (deoxyhemoglobin)
Reversible CO2 transport (at lungs)
■ HbCO2 Hb + CO2
■ reaction occurs at the lungs where the PCO2 is low
Reversible O2 transport (at tissues)
■ HbO2 Hb + O2
■ Reaction occurs at the tissues where the PO2 is low
■ the reaction is also enhanced by:
■ Body temperature
■ P CO2
■ ¯ pH
■ ¯ PO2
Carbaminohemoglobin
■ With low oxygen (peripheral capillaries):
■ hemoglobin releases O2 into surrounding tissues
■ binds carbon dioxide and carries it to lungs
Reversible CO2 Transport (at tissues)
■ The binding of O2 and CO2 are reversible and appropriate:
■ Hb + CO2 HbCO2 (Carbamino Hb)
■ reaction occurs at the tissues, where the PCO2 is high
Reversible O2 Transport (at lungs)
■ Hb + O2 HbO2 (Oxy hemoglobin)
■ Reaction occurs at the lungs where the PO2 is high
Carbon monoxide
■ O2 competes with CO (carbon monoxide) which has a higher affinity for Hb then O2
■ Hb + CO HbCO
Carboxyhemoglobin
Blocker of O2 transport
Anemia
■ Hematocrit or hemoglobin levels are below normal
Recycling RBCs
■ 1% of circulating RBCs wear out per day:
■ about 3 million RBCs per second
■ Macrophages of liver, spleen, and bone marrow:
■ monitor infections (tissue homeostasis, wound/bone healing liver inflammation)
■ engulf RBCs before membranes rupture (hemolyze)
Hemoglobinuria
Hemoglobin and its breakdown products in urine due to excess hemolysis in blood stream
Hematuria
whole red blood cells in urine due to kidney or tissue damage
Phagocytes break hemoglobin into components:
■ globular proteins to amino acids
■ heme to biliverdin
Iron recycling
■ Large quantities of free iron are toxic
■ Iron is bound to:
■ transport proteins (transferrin)
■ storage proteins (ferritin and hemosiderin) in muscle, liver and spleen
■ Transported back to the bone marrow by transferrin
Breakdown of biliverdin
■ Biliverdin (green) is converted to
bilirubin (yellow)
■ Bilirubin is:
■ excreted by liver (bile)
■ jaundice is caused by bilirubin buildup
■ converted by intestinal bacteria to urobilin (yellow)
■ urobilin is reabsorbed in the blood and then excreted by the liver
■ Any remaining urobilin is converted to stericobilin which gives feces its brown color
RBC maturation- erythropoiesis
■ Red blood cell formation
■ Occurs only in red bone marrow (myeloid tissue)
■ Stem cells mature to become RBCs
Hematopoietic stem cells (hemocytoblasts)
■ Stem cells in bone marrow divide to produce:
■ myeloid stem cells:
■ become RBCs, some WBCs
■ lymphoid stem cells:
■ become lymphocytes
Stages of RBC maturation
■ Myeloid stem cell
■ Proerythroblast
■ Erythroblasts
■ Reticulocyte
■ Mature RBC
■ Takes about 15 days
Building RBCs require:
■ amino acids
■ iron
■ vitamins B12, B6, and folic acid
Pernicious anemia
■ Low RBC production
■ Due to unavailability of vitamin B12 due to:
■ B12 deficiency
■ lack of intrinsic factor
■ absorption problem
Stimulating hormones
■ Erythropoietin (EPO)
■ Also called erythropoiesis-stimulating hormone:
■ Stimulates both
■ Rate of stem cell division (ten fold)
■ Rate of Hb production (maturation)
■ secreted mostly from the kidneys when oxygen in the tissues of the kidneys is low (hypoxia)
■ due to disease or high altitude
■ EPO enters the blood and is transported to myeloid tissues and acts to
■ Increase hemocytoblast proliferation and
■ directs them toward increased erythropoiesis
■ Stimulated by testosterone
Classification of anemias
■ A. Congenital - Inherited
■ B. Hemolytic - marked by excessive RBC destruction
■ C. Aplastic - red marrow shutdown
■ D. Hemorrhagic - excessive blood loss
■ E. Nutritional - due to dietary deficiencies
Congenital anemia
■ are inherited due to genetic mutations and include:
■ Sickle cell
■ a and b Thalassemias
■ Sickle cell Anemia
■ Due to a point mutation in the B-globin gene
■ Causes hemoglobin - form long inflexible chains when O2 is low
■ Long inflexible cells clog arteries
■ More common in people of African decent
■ helps resistance to malaria
■ a and b Thalassemias
■ Deficient synthesis of hemoglobin
■ More common in people of Mediterranean decent
Hemolytic anemias
■ marked by excessive RBC destruction
■ Fetal hemolytic disease (erythroblastosis a Rh incompatibility)
■ Malaria (protozoal parasite)
■ Gram-positive bacteria as in Streptococcal Disease
Aplastic anemias
■ bone marrow shutdown caused by:
■ exposure to toxic chemicals (chloramphenicol, a broad-spectrum antibiotic)
■ Radiation exposure
■ Hypersensitivity reactions to drugs
■ All cell lines affected
■ Anemia; clotting and immunity defects
■ Treated short-term with transfusions; long-term with transplanted stem cells
Hemorrhagic anemia
■ Blood loss rapid (e.g., stab wound)
■ Treated by blood replacement
■ Chronic hemorrhagic anemia
■ Slight but persistent blood loss
■ Hemorrhoids, bleeding ulcer
■ Primary problem treated
Nutritional anemia
■ Most common
■ Associated with vitamin deficiencies
■ Most common are:
■ Iron Deficiency Anemia
■ Pernicious Anemia
■ Folic Acid Anemia
Iron deficiency
■ cells are microcytic (small) (¯ MCV)
■ cells are hypochromic (¯ MCH) (pale in color)
■ females of reproductive age are at highest risk;
■ need Fe2+ due to menstrual loss
■ Iron supplements to treat
Pernicious Anemia
■ Vitamin B12 deficiency
■ cells are macrocytic (large)
■ Cells have fragile membranes
■ Patients also develop a thick, beefy tongue
■ Patients also develop neurologic S & S including:
■ Confusion
■ Disorientation
■ forgetfulness
■ Need Vit. B12 (by injection or nasal gel)
Folic acid anemia
■ same S & S as pernicious, but without neurologic S&S
■ Also essential in first trimester women for fetus CNS development
■ Need folic acid
Renal anemia
o Lack of EPO
o Often accompanies renal disease
o Treated with synthetic EPO
Reticulocytes
■ As myeloid stem cell transforms
■ 1.Ribosomes synthesized
■ 2.Hemoglobin synthesized; iron accumulates
■ 3.Ejection of nucleus; formation of reticulocyte (young RBC)
■ Normal Reticulocyte number = .5-2% of total RBC
■ Reticulocyte count indicates rate of RBC formation
WBCs
■ Also called leukocytes
■ Do not have hemoglobin
■ Do have nuclei and other organelles
WBC functions
■ Defend against pathogens
■ Remove toxins
■ Attack abnormal cells
WBC movement
■ Most WBCs in:
■ connective tissue proper
■ lymphatic system organs
■ Small numbers in blood:
■ 5000 to 11000 per microliter
Circulating WBCs
- Migrate out of bloodstream
- Have amoeboid movement
- Attracted to chemical stimuli (positive chemotaxis)
- Some are phagocytic:
■ neutrophils, eosinophils, and monocytes
5 types of WBCs
A. Granulocytes
1. Neutrophils
2. Eosinophils
3. Basophils
B. Agranulocytes
1. Monocytes
2. Lymphocytes - Both B and T Lymphs
• Decreasing abundance in blood. Never let monkeys eat bananas
Neutrophils
-Also called polymorphonuclear leukocytes
50–70% of circulating WBCs (12-14 um in diameter) (called “polymorphs” or “polys”)
-Pale cytoplasm has numerous small, purple granules with:
■ lysosomal enzymes
■ bactericides (hydrogen peroxide and superoxide)
-Mature are multilobed, polymorphic nucleus; (resembles Beads on a string) – Called segs (Segmented nucleus)
-Immature neutrophils are called Bands
■ their nucleus is not fully segmented (looks like a band)
-Increased bands suggests active infection
Neutrophil Action
■ Very Aggressive, first to attack “antibody marked” bacteria
and increase in number
■ Engulf pathogens
■ Digest pathogens
■ Release prostaglandins and leukotrienes
■ Form pus
Degranulation
■ Removing granules from mast cells
■ caused by fusion with lysosomes
■ Occurs in Granulocytes, mast cells and some lymphocytes
■ Defensins:
■ peptides from lysosomes
■ attack pathogen membranes
Eosinophil
■ Also called acidophils
■ 2–4% of circulating WBCs (12-14 um in diameter)
■ contain Red granules.
■ Bi-lobed nucleus
■ Phagocytic microphage
■ Attack large parasites and “antibody marked” objects
■ Excrete toxic compounds:
■ nitric oxide
■ cytotoxic enzymes
Eosinophil actions
■ Are sensitive to allergens
■ Control inflammation with enzymes that counteract inflammatory effects of neutrophils and mast cells
■ Numbers increase in allergy, asthma, invasive parasitic disease, eosinophilic gastroenteritis
Basophils
■ Are type of WBC (least common type of granulocyte)
■ bilobed nucleus most often not visible due to large numbers of large, purple granules.
■ Are less than 1% of circulating WBCs
■ Accumulate in damaged tissue
■ non phagocytic (8-10) um in diameter
■ Rare, because once formed they leave the blood and become similar to mast cells in Connective Tissue.
Basophil actions
■ Release histamine:
■ dilates blood vessels
■ Release heparin:
■ prevents blood clotting
■ Release chemotactic factors:
■ inflammatory promoters
Monocytes
■ 2–8% of circulating WBCs (15-25 um in diameter)
■ Are large and spherical with an indented nucleus
■ Enter peripheral tissues and become phagocytic macrophages
Macrophage actions
■ Engulf large particles and bacteria
■ crucial against viruses, intracellular bacterial parasites, and chronic infections
■ Secrete substances that attract immune system cells and fibroblasts to injured area
■ Activate lymphocytes to mount an immune response
Lymphocytes
Responsible for defenses in immune response
■ 20–30% of circulating WBCs
■ 8-10 um in diameter but vary in size with small lymphs averaging 6-9 um and large lymphs 10-14um
■ large, round nucleus that takes up most of the cell
■ small amount of blue cytoplasm
■ Migrate in and out of blood
■ Mostly in connective tissues and lymphatic organs
■ non phagocytic
2 classes of lymphocytes
-T cells
-B cells
T-cells
■ 80% T-Lymphs
■ Cell-mediated immunity (CMI) - Lymphokine production
■ Attack foreign cells
B cells
■ 20% B-Lymphs
■ responsible for humoral or Antibody Mediated Immunity (AMI) Differentiate into plasma cells
■ Synthesize antibodies
■ Tend to increase in number in acute viral infection or in lymphocytic leukemia
RBCs: WBCs ratio
1000: 1
Most numerous WBC and role
Neutrophil- engulfs bacteria
WBC production
■ All blood cells originate from hemocytoblasts:
■ which produce myeloid stem cells and lymphoid lymphocyte cells
Myeloid stem cells
■ Differentiate into progenitor cells:
■ which produce all WBCs except lymphocytes
Lymphopoiesis
Production of lymphocytes by lymphoid progenitor cells
Lymphopoiesis
Production of lymphocytes by lymphoid progenitor cells
WBC development
■ WBCs, except monocytes:
■ develop fully in bone marrow
■ Monocytes:
■ develop into macrophages in peripheral tissues
■ Granulocytes stored in bone marrow
■ 3 times more WBCs produced than RBCs
■ Shorter life span; die fighting microbes
■ Progression of agranulocytes differs
■ Monocytes – live several months
■ Lymphocytes – live few hours to decades
4 colony- stimulating factors (CSFs)
■ Hormones that regulate blood cell populations:
1.M-CSF:
■ stimulates monocyte production
2.G-CSF:
■ stimulates granulocyte production
■ neutrophils, eosinophils, and basophils
3.GM-CSF:
■ stimulates granulocyte and monocyte production
4.Multi-CSF:
■ stimulates production of granulocytes, monocytes, platelets, and RBCs
Platelets
■ Cell fragments involved in human clotting system
■ Nonmammalian vertebrates have thrombocytes (nucleated cells)
Platelet circulation
■ Circulates for 9–12 days
■ Are removed by plateletpheresis
■ many are reserved for emergencies
3 functions of platelets
- Release important clotting chemicals
• Granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF) - Temporarily patch damaged vessel walls
- Actively contract tissue after fibrin clot formation
Platelet production
■ Also called thrombocytopoiesis:
■ occurs in bone marrow
Megakaryocytes
■ large bone marrow cells
■ Manufacture platelets from cytoplasm
Hemostasis
■ Fast series of reactions for stoppage of bleeding
■ Requires clotting factors, and substances released by platelets and injured tissues
3 steps of hemostasis
1) vascular phase
2) platelet phase
3) coagulation phase
2 steps of vascular phase
- Pain reflexes and direct injury to vascular cause smooth muscle and endothelial cells cause both of them to contract:
• expose basal lamina to bloodstream
• Restrict blood flow - Endothelial cells release:
■ chemical factors:
■ ADP, tissue factor, and prostacyclin
■ local stimuli:
■ endothelins
■ stimulate smooth muscle contraction and endothelial cell division
Platelet phase
■ Begins within 15 seconds after start of vascular spasm
■ Platelet adhesion (attachment):
■ to sticky endothelial surfaces
■ to basal laminae
■ to exposed collagen fibers via plasma protein von Willebrand factor
■ Platelet aggregation (stick together):
■ forms platelet plug
■ closes small injuries
Platelet plug: size restriction
■ Two mechanisms limit clot size
■ Swift removal and dilution of clotting factors
■ Inhibition of activated clotting factors
■ Prostacyclin:
■ released by endothelial cells
■ inhibits platelet aggregation
■ Inhibitory compounds:
■ released by other white blood cells
■ Negative (inhibitory) feedback:
■ from serotonin by blocking ADP
■ Stops development of blood clot
Coagulation phase
■ Begins 30 seconds or more after the injury
■ Blood clotting (coagulation):
■ Involves a series of steps
■ converts circulating fibrinogen into insoluble fibrin
Blood clot
■ Fibrin network
■ Covers platelet plug
■ Traps blood cells
■ Seals off area
Cascade reactions
■ During coagulation phase
■ Chain reactions of enzymes and proenzymes
Coagulation
■ Three phases of coagulation
■ Prothrombin activator formed in both intrinsic and extrinsic pathways
■ Prothrombin converted to enzyme thrombin
■ Thrombin catalyzes fibrinogen à fibrin
3 phase of coagulation
■ Phase 1
■ Extrinsic pathway:
■ outside blood stream
■ Involves Tissue factor
■ Intrinsic pathway:
■ begins with circulating proenzymes
■ within bloodstream
■ Involves Platelet factor
■ Phases 2:
■ Activation of Thrombin
■ Phases 3:
■ Formation of final clot
Coagulation phase 1: extrinsic pathway
■ Very fast (seconds)
■ Damaged cells from outside the blood vessel release tissue factor (TF, Factor III)
■ TF + other compounds including Ca2+ = enzyme complex
■ Activates Factor VII-VIIa
Coagulation phase 2: intrinsic factor
■ Slower (several minutes)
■ Does not require stim. From outside the vessel
■ Activation of enzymes by collagen of damaged vessel
■ Platelets release factors (e.g., PF–3)
■ Series of reactions which include factors VIII (antihemophilic factor) and IX (Christmas factor) activate Factor X
■ Requires Ca2+
Functions of thrombin
■ Stimulates activation and aggregation of platelets
■ Accelerates the formation of prothrombin activator (prothrombinase)
■ forms positive feedback loop (intrinsic and extrinsic):
■ accelerates clotting
■ Also has anticoagulant and fibrolytic effects
■ Activates Plasminogen away from the clot
Clotting: area restriction
- Anticoagulants (plasma proteins):
- antithrombin-III – inhibits thrombin and other clotting factors
- alpha-2-macroglobulin – inhibits thrombin - Heparin – clinically used to prevent clotting
– from basophils and mast cells
- Speeds the activation of antithrombin-III - Prostacyclin
- Inhibits platelet aggregation
- Opposes the action of thrombin, ADP and other factors
Clot retraction (syneresis)
■ After clot has formed:
■ Platelets contract and pull torn area together and reduce the size of the wound
■ Takes 30–60 minutes
■ A fibrinous exudate is secreted (scab)
Fibriniolysis
■ Slow process of dissolving blood clots:
■ thrombin and tissue plasminogen activator (t-PA):
■ activate plasminogen
■ Plasminogen produces plasmin:
■ digests fibrin strands
Thrombus
clot formed inside a vessel and attached to the vessel wall
Thrombosis
the formation of a clot inside a vessel
Embolus
usually foreign (from outside the vascular compartment) and travels
Embolism
embolus obstructing a vesse
