Chapter 18 - Blood Flashcards
T/F - Blood is considered a connective tissue
True
Plasma
- Non-living fluid matrix
- The fluid portion of the blood containing plasma proteins and dissolved solutes
- 90% water
- > 100 dissolved solutes including nutrients, gases, hormones, wastes, proteins, inorganic ions
- Plasma proteins are most abundant solutes –> remain in blood and are not taken up by cells –> Proteins produced mostly by liver (ex: albumin, ⍺ & β- globulins, fibrinogen, and other proteins involved in clotting) –> 60% albumin, 36% globulins, 4% fibrinogen
- Some are produced by leukocytes (ex: gamma-globulins) and other organs (ex: regulatory protein)
Formed elements
Living blood “cells” suspended in plasma (fluid portion of blood)
- Include erythrocytes, leukocytes, and thrombocytes (platelets)
- WBCs are the only complete cells
- RBCs have no nuclei or other organelles
- Platelets are cell fragments
- Most formed elements survive in bloodstream only few days
- Most blood cells originate in bone marrow and do not divide
Color of blood when oxygen-rich and poor
- Oxygen-rich –> bright red/scarlet
- Oxygen- poor –> dark red
Explain the bluish appearance of our veins
- Bc of the fact that we can see the blood moving the superficial veins in the skin
- Lower-energy light wavelengths (ex: red) are absorbed by the skin and higher-energy wavelengths like blue are reflected back to the eye
What is the average and range of blood?
- Average volume –> 5 L
- Range ~4 - 6 L
- 5-6L for males and 4-5 L for females (lower because menstrual cycle)
- Sustaining a normal blood volume is important in maintaining blood pressure
- ~8% of body weight
Viscosity increases if the amount of substances, especially _________, increases
Erythrocytes
Plasma concentration
Relative concentration of solutes (proteins, ions, etc) in plasma
- Normally about 0.9% concentration
- Determines if fluids move in or out of the plasma by osmoses as blood is transported through capillaries –> ex: person is dehydrated –> plasma becomes hypertonic and fluid moves into the plasma from surrounding tissues
- Used when determining IV solution concentrations, which are usually isotonic (same solute concentration) to plasma
Temperature of blood
- Almost 1 degree C (or 2 degree F) higher than measured body temp
- Body = 37 degree C = 98.6 degree F
- Blood = 38 degree C - 100.4 degree F
Blood pH
- Between 7.35 - 7.45
- Plasma proteins have 3D shape that is dependent upon H+ concentrations
- The neurtral/normal range for our body
- pH < 7.35 in blood = acid –> acidosis
- pH> 7.45 in blood = base –> alkalosis
Layers and percentages of each of blood
- Plasma on top (~55%)
- WBCs and platelets in buffy coat (<1%)
- Erythrocytes on bottom (~45%)
Whole blood
Plasma membrane and formed elements
- Can be separated into liquid.cellular components using a centrifuge
Hematocrit
Percent of blood volume that is RBC
- 47% +/- 5% for males
- 42% +/- 5% for females
- Low level means anemia
- High level means patient is dehydrated, lives in high altitude, and participated in blood doping
- Influenced by testosterone by stimulating the kidney to produce the hormone erythropoietin (EOP) –> promotes erythrocyte production –> higher hematocrit
Why is blood sticky and metalic?
- Sticky because it has glucose
- Metalic because there is iron in erythrocytes
What are the functions of blood?
1.) Distributing substances
- Deliver O2 and nutrients to body cells
- Transport waste to lungs and kidneys for elimination
- Transporting hormones
2.) Regulating blood levels of substances
- Maintaining body temperature by absorbing (especially skeletal muscle cells) and distributing heat
- Maintaining normal pH using buffers; alkaline reserve of bicarbonate ions –> blood absorbs acids and base from body cells and blood maintains chemical buffers that bind and release H+ to maintain pH until the excess is eliminated from body
- Maintaining adequate fluid volume in the circulatory system –> osmotic pressure pull fluid back into capillaries to help maintain normal fluid balance
3.) Protection
- Preventing blood loss using clotting
- Preventing infection with antibodies, complement proteins, WBC
Colloid osmotic pressure (COP)
Osmotic pressure exerted by plasma proteins
- Responsible for draining fluids into the blood and preventing excess fluid loss from blood capillaries into the ISF –> helps maintain blood volume/ pressure
Albumin
- Smallest and most abundant plasma protein
- Has the greatest colloid osmotic pressure to maintain because it’s the most abundant
- Transport substances within blood (ex: ions, hormones, some lipids)
- ~58-60% of plasma proteins
- Substance carrier
- Blood buffer –> can act as a sponge if there are pH changes –> can absorb acid or release acid if not enough
- May bind to a protein to inactivate drugs –> control concentration
Globulins
~ 37% of plasma proteins
- Second largest group of plasma proteins
- ⍺-globulins (smaller) and β-globulins (larger) primarily bind and transport certain lipids, hormones, some metals, and ions
- Gamma-globulins, immunoglobulins/antibodies: Play a part in the body’s defenses
- Proteins that are used as antibodies and form antibodies
- Can attach to bacteria to inactivate it and mark the bacteria for distraction
Fibrinogen
- ~4% of plasma proteins
- A clotting protein
- After trauma, fibrinogen is converted into long, insoluble strands of fibrin (which helps form a blood clot)
- Associated with the function of platelets –> platelets are used when there is a breach in blood vessel –> platelets try to seal and fibrogen forms a sticky net to hold them in palce
What are the plasma proteins in plasma?
1.) Albumin
2.) Globulins
3.) Fibrinogen
4.) Regulatory proteins
What are the other solutes in plasma?
1.) Electrolytes
2.) Nutrients
3.) Respiratory gases
4.) Wastes
Erythrocytes (RBCs)
- Small, flexible, biconcave disks, anucleate, no organelles
- Diameters larger than some capillaries
- Packed with hemoglobin for gas transport (>97% hemoglobin)
- Contain plasma membrane protein spectrin (provides flexibility to change shape) and other proteins
- Major contributor to blood viscosity
- No mitochondria (bc it would take from the O2 being transported), ATP production anaerobic, do not consume O2 they transport
- Hemoglobin binds reversibly with oxycen
- Males = 13-18g/100mL; Females = 12-16g/100 mL
Oxygenated: Maximally loaded with O2
Deoxygenated: When some O2 is lost
Hemoglobin structure
- Gobin composed of 4 polypeptide chains (globins) (2 ⍺ and 2 β chains)
- 4 heme groups per molecule of hemoglobin –> has 4 Fe 2+ – can bind up to 4 molecules of O2 (weak attachment to quickly attach/release)
- CO2 binds to the globin protein molecule
Heme: portion of hemoglobin that binds iron, which transports O2 –> made of a porphyrin ring with Fe 2+ in the center –> O2 binds to Fe+ - Heme gives color
- 250 million Hb in each RBC
What is the ferrous state of iron? What is the ferric state of iron?
Ferrous state of iron = Fe 2+ (only state in which oxygen can bind to)
Ferric state of iron = Fe 3+
What are some terms used to describe O2 loading/unloading and
- O2 loading in lungs (oxygen is binding to hemoglobin) –> produces oxyhemoglobin (ruby red)
- O2 unloading in tissues (oxygen released from hemoglobin) –> produces deoxyhemoglobin or reduced hemoglobin (dark red)
- CO2 loading in tissues (CO2 may bind to globulin) –> 20% of CO2 in blood bind to Hb –> Carbaminohemoglobin
Hematopoiesis
Blood cell formation in red bone marrow
- Composed of reticular connective tissue and blood sinusoids
- In adults, found in axial skeleton, girdles, and proximal epiphysis of humerus and femur
- Hematopoietic stem cells (hemocytoplasts)
- Hormones and growth factors push cell toward specific pathway and blood cell development
- Committed cells cannot change
Hematopoietic stem cells (hemocytoplasts)
Give rise to all formed elements
- A cell with organelles
- Throughout the steps of hematopoiesis, the organelles are being degraded or taken out
Multi-colony-stimulating factor (multi-CSF)
- Growth factor
- Increases the formation of erythrocytes, granulocytes, monocytes, and platelets from myeloid stem cells
Grannulocyte-macrophage colony-stimulating factor (GM-CSF)
- Growth factor
- Accelerates the formation of all granulocytes and monocytes from their progenitor cells
Granulocyte colony-stimulating factor (G-CSF)
- Growth factor
- Stimulates the formation of granulocytes from myoblast cells
Macrophage colony-stimulating factor (M-CSF)
- Growth factor
- Stimulates the production of monocytes from monoblasts
Thrombopoietin
- Growth factor
- Stimulates both the production of megakaryocytes in the red bone marrow and subsequent formation of platelets
Erythropoietin (EPO)
- Hormone –> made primarily by the kidneys
- Increases the production and maturation of erythrocyte progenitor and erythroblast cells
Colony-stimulating factors (CSFs)/ colony-forming units (CFU)
Substances that influence the maturation and division of hematopoietic stem cells
Erythropoiesis, what is it?
The creation of RBC
What are the steps and changes in erythropoiesis?
1.) Hemocytoblast (hematopoietic stem cell) –> myeloid line
2.) Myeloid stem cell –> Multi-CSF Multi-colony-stimulating factor helps select erythropoiesis
3.) Progenitor cell
4.) Proerythroblast
- A large, nucleated cell
- Committed cell
- In 15 days it develops into the next few stages and then reticulocytes
5.) Early erythroblast (basophilic erythroblast)
- A slightly smaller cell that has ribosomes producing hemoglobin protein in its cytosol
6.) Late erythroblast (polychromatophilic erythroblast)
7.) Normoblast (orthochromatic erythroblast)
- A smaller cell with more hemoglobin the cytosol
- Has a nucleus (last stage with a nucleus)
8.) Reticulocyte
- No nucleus as it was ejected in the normoblast phase
- An immature erythrocyte
- Has lost all organelles except some ribosomes, so it can continue for a short time to produce hemoglobin through protein synthesis
- Some finish maturation while circulating in blood vessel –> 1-2 days after entering circulation, ribosomes degenerate and reticulocyte matures
- Overproduction of RBC could lead to too many not mature yet reticulocytes
- Reticulocyte count = rate of RBC formation
9.) Erythrocyte
- No nucleus or organelles
- Essentially a plasma membrane “bag” with hemoglobin
- Can live for only 120 days
- Can do full-function
What does the myeloid line help create?
- Erythrocytes
- All leukocytes (EXCEPT lymphocytes) –> includes granulocytes ((Eosinophil, basophil, neutrophil) and monocytes
What does the lymphoid line help create?
- Lymphocytes
Steps for thrombopoiesis (platelet formation)
1.) Hemocytoblast (hematopoietic stem cell)
2.) Myeloid stem cell
3.) Progenitor cell is formed with the guide of Multi-CSF
4.) Megakaryoblast
- A committed cell
5.) Promegakaryocyte produced with help of thrombopoietin
6.) Megakaryocyte produced with help of thrombopoietin
- Large in size and has dense, multilobed nucleus
- Have long extensions that extend through blood vessel wall between endothelial cells in red bone marrow –> called proplatelets
- Megakaryocytes remain in red bone marrow but some may circulate through the lung vasculature and release platelets (as seen in mouse model)
7.) Platelets formed with help of thrombopoietin
- The force of the blood flow slices
Steps for making granulocytes
1.) Hemocytoblast (hematopoietic stem cell)
2.) Myeloid stem cell and Multi-CSF leads production towards leukopoiesis
3.) Progenitor cell is formed with the guide of GM-CSF
4.) G-CSF leads production to give rise to myeloblast
5.) Becomes promyelocytes, which will differentiate into…
- Eosinophilic myelocyte
- Basophilic myelocyte
- Neutrophilic myelocyte
6.) These will become granulocytes…
- Eosinophil
- Basophil
- Neutrophil
Steps for making monocytes
1.) Hemocytoblast (hematopoietic stem cell)
2.) Myeloid stem cell and Multi-CSF leads production towards leukopoiesis
3.) Progenitor cell is formed with the guide of GM-CSF
4.) M-CSF leads production to give rise to monoblast
5.) M-CSF leads development into promonocyte
6.) Will develop into monocyte
- A white blood cell that develops into a macrophage and phagocytize bacteria and viruses
Steps for lymphocyte production
1.) Hemocytoblast (hematopoietic stem cell)
2.) Lymphoid stem cell
- Stimulated by Multi-CSF and GM-CSF to form a progenitor cell
3.) Will differentiate into either…
- B-lymphoblast
- T-lymphoblast
4.) Each will become corresponding…
- B-lymphocytes
- T-lymphocyte
Steps for natural killer cell production
1.) Hemocytoblast (hematopoietic stem cell)
2.) Lymphoid stem cell
3.) Will differentiate into natural killer cell
What controls the rate of erythropoiesis and how?
- Erythropoietin (EPO) hormone controls rate
- By increasing erythrocyte formation rate
What can too few or too many RBC lead to?
- Too few RBC –> leads to tissue hypoxia
- Too many RBCs –> increases blood viscosity
Balance between RBC production and destruction depends on…
- Hormonal controls
Erythropoiesis requires adequate supplies of…
1.) Iron –> to bond O2
- 65% in hemoglobin; rest in liver, spleen, and bone marrow
- Free iron ions are toxic (may lead to scaring of liver) and are transported in blood-bound protein called transferrin
- Stored in calls as ferritin (binds many irons) and hemosiderin (a collection of ferritins all binding iron to them)
2.) Nutrients
- Amino acids –> to make globulin
- Lipids, carbohydrates
3.) B vitamins, especially B12 –> without B12, the cell goes G1 (double up on everything except DNA) and reach S phase (replicate DNA) but process stops, leaving big cells with incomplete process
- The stomach secretes IF (intrinsic factor) –> only after IF binds that B12 can be absorbed in small intestine
Hormonal control of erythropoiesis
Hormone erythropoietin (EPO)
- Direct stimulus for erythropoiesis
- Always small about in blood to maintain basal rate
- High RBC or O2 levels depress production
- Released by kidneys (Some from liver) in response to hypoxia
- Adrenal gland and testes can secrete testosterone –> stimulates the kidney to produce more EPO
- Effects of EPO include rapid maturation of committed marrow cells and increased circulating reticulocyte count in 1-2 days
Causes of hypoxia
Hypoxia: Lack of oxygen in tissue
- Decreased RBC numbers due to hemorrhage or increased destruction
- Insufficient hemoglobin per RBC –> iron deficiency (doesn’t matter if enough RBC, only matters if hemoglobin inside works as well)
- Reduced availability of O2 (ex: high altitudes)
Fate and destruction of erythrocytes (steps)
1.) Aged erythrocytes broken down into their 3 components in the liver and spleen
- Globin protein is broken down into free amino acids –> body can use to form new proteins
- Iron is removed from heme
- Heme group is converted within macrophages first into a green pigment (biliverdin) –> converted in macrophages into yellowish pigment (bilirubin)
2.) Bilirubin transported by albumin in the blood
- Jaundice is the accumulation of bilirubin in the body
3.) Bilirubin removed from blood by liver
4.) Bile (containing bilirubin) excreted into small intestine
- Bile –> a secretion that facilitates digestion
- Bilirubin eliminated from liver into small intestine
5.) Bilirubin converted to urobilinogen in small intestine
6a.) Most urobilinogen is converted to stercobilin in the large intestine and expelled in feces
- Stercobilin: A brown pigment that is expelled from the body as a component of feces
6b.) Some urobilinogen reabsorbed into the blood, converted to urobilin (yellow pigment excreted by kidneys), and excreted in urine
What are the 3 causes of anemia?
- Blood loss
- low RBC production
- High RBC destruction
Causes of anemia: blood loss
1.) Hemorragic anemia
- Blood loss rapid (ex: stab)
- Treated by blood replacement
2.) Chronic hemorrhagic anemia
- Slight but persistent blood loss
Causes of anemia: Low RBC production
1.) Iron-deficiency anemia
- Due to hemorrhagic anemia, or iron intake, impaired absorption
- Treat with iron sublements
- Lead to microcytic, hypochromic RBC
2.) Renal anemia - Lack of EPO
- Often accompanies renal disease
- Treated with synthetic EPO
3.) Aplastic anemia
- Destruction or inhibition of red marrow by drugs, chemicals, radiation, viruses
- Cause unknown and all cell lines affected
- Treated short-term –> transfusions
- Treated Long-term –> transplanted stem cells
Causes of anemia: High RBC destruction
1.) Hemolytic anemias
- Due to Hb abnormalities, incompatible transfusions, infections
2.) Sickle-cell anemia –> genetic defect leading to abnormal
- One amino acid is wrong in the globin beta chain
- RBC rupture easily and block small vessels because they’re not flexible –> poor O2 delivery and pain
Leukocytes
- Make up <1% of total blood volume –> 4,800 - 10,800 WBCs/ μL blood
- Defense against disease
- Leave capillaries via diapedesis
- Move through tissue spaces by ameboid motion and positive chemotaxis (going towards higher concentration)
- Has nucleus and organelles, but no hemoglobin
- Motile and flexible
- Most in tissues
Leukocytosis
- WBC count over 11,000/mm3
- Normal response to infection
Diapedesis
- Process of squeezing through blood vessel wall between endothelial cells
- How they enter tissues from blood vessels
Chemotaxis
- Attraction of leukocytes to chemicals at an infection site
What are the two categories of leukocytes? What do they contain?
1.) Granulocytes: visible cytoplasmic granules
- Neutrophils
- Eosinophils
- Basophils
2.) Agranulocutes: No visible cytoplasmic granules –> Have smaller granules that are not visible with light microscope
- Lymphocytes
- Monocutes
Decreasing abundance of leukocytes in blood (order)
NEVER LET MONKEYS EAT BANANAS
N- Neutrophils (most abundant) (50-70%)
L- lymphocytes (25-45%)
M - Monocytes (3-8%)
E- Eosinophil (2-4%)
B- Basophil (least abundant) (0.5-1%)
Granulocytes
- Larger and shorter-lived than RBC
- Lobed nuclei
- Cytoplasmic granules stain specifically with Wright’s stain
- All phagocytic to some degree
Neutrophils
- Most numerous WBC
- Also called Polymorphonuclear leukocytes (PMNs or polys)
- Granules stain lilac –> contain hydrolytic enzymes or defensins
- 3-6 lobes in nucleus
- Twice the size of RBCs
- Phagocytic –> “bacteria slayers”
- Pus = dead neutrophils
Left-shifted differential
- The increased presence of immature neutrophils
Neutropenia
A decrease in neutrophils
Eosinophils
- Red-staining –> granules
- Bilobed nucleus connected by a thin string
- Granules lysosome-like –> release enzymes to digest parasitic worms
- Role in allergies and asthma
- Role in modulating immune response
Basophils
- Rarest WBC
- Nucleus is deep purple with 1-2 constrictions
- Large, purplish-black violet (basophilic) granules contain histamine
- Functionally similar to mast cells
Histamine
Inflammatory chemical that acts as a vasodilator to attract WBCs to inflamed sites
- Increases capillary permeability
- Cause classic allergic symptoms
Agranulocytes
- Lack of visible cytoplasmic granules
- Spherical or kidney-shaped nuclei
Lymphocytes
- Second most numerous WBC
- Large, dark purple circular nuclei with thin rim of blue cytoplasm
- Mostly in lymphoid tissue (ex: lymph nodes, spleen)
- Few circulate in blood
- Crucial to immunity
- Two types
1.) T lymphocytes (T cells): Act against virus-infected cells and tumor cells –> made in thymus
2.) B lymphocytes (B cells): Give rise to plasma cells, which produce antibodies –> from bone marrow
Monocytes
- Largest leukocytes
- Abundant pale-blue cytoplasm
- Dark purple staining
- U-/C- or kidney-shaped nuclei
- Leave circulation after 3 days, enters tissues , differentiates into macrophages
- Actively phagocytic cells –> crucial against viruses, intracellular bacterial parasities, and chronic infections
- Activate lymphocytes to mount an immune response
Leukopoiesis
Production of WBC
- Stimulated by 2 types of chemical messengers from red bone marrow and mature WBCs
1.) Interleukins (ex: IL-3, IL-5)
2.) Colony-stimulating factors (CSFs) - Named for WBC type they stimulate
- All leukocytes originate from hemocytoblasts
Leukopenia
- Abnormally low WBC count - Drug induced
Leukemias
- Cancer –> overproduction of abnormal WBCs
- Named according to the abnormal WBC clone involved
- Myeloid leukemia –> myeloblast descendants
- Lymphocytic leukemia –> involves lymphocytes
Acute leukemia: Derives from stem cells –> primarily affects children
Chronic leukemia: More prevalent in older people
Platelets
- Cytoplasmic fragments (break off from megakaryocytes)
- No nucleus
- Blue staining outer region
- Purple granules
- Normal –> 150,000 - 400,000 platelets/ml of blood
- Temporary blood platelet
- Circulating platelets are kept inactive and mobile by nitric oxide (NO) and prostacyclin from endothelial cells lining blood vessels
- Degenerate in ab 10 days
- Formation regulated by thrombopoietin
Hemostasis
- Fast series of reactions for stoppage of bleeding
- Requires clotting factors and substances released by platelets and injured tissues
- 3 steps
1.) Vascular spasm
2.) Platelet plug formation
3.) Coagulation (blood clotting)
Hemostasis - Vascular Spasm step
- Vasoconstriction of damaged blood vessel
- Triggered by –> Injury to vascular smooth muscle, chemicals released by endothelial cells and platelets, pain reflexes
- Most effective in smaller blood vessels –> limits blood leakage
- Lasts from few to many minutes
- Platelets and endothelial cells release chemicals that stimulates further constriction
- Greater vasoconstriction with greater vessel damage
- Achieved by –> nerve reflexes, secretion of endothelin (by endothelial cells and affect smooth muscle)
- Endothelium cells secrete nitric oxide and prostacyclin —> both cause vasodilation
Hemostasis - Platelet plug formation
- Positive feedback cycle
- Damaged endothelium exposes collagen fibers
- Platelets stick to collagen fibers via plasma protein –> Von Willebrand factor
- Swell, become spiked and sticky –> release chemical messengers –> ADP causes more platelets to stick and release contents –> serotonin and thromboxane A2 enhance vascular spasm and platelet aggregation
- Many platelets aggregate and close off injury
- Have two receptor types –> Glycoprotein 1b, glycoprotein 2b/3a
Hemostasis - Coagulation
- Fibrin –> reinforces platelet plug with threads to form a mesh –> fibrin comes from soluble precursor fibrinogen
- Blood transformed from liquid to gel
- Series of reactions using clotting factors (procoagulants)
- # 1 - 13 –> most plasma proteins
- Vitamin K needed to synthesize 4 of them
Which factors are considered proteases?
- Factors 7 and 9
