Flashcards in Blood Deck (159):
A connective tissue composed of a liquid extracellular matrix called plasma which functions to dissolve and suspend cells and cell fragments.
Functions of blood
Temperature and pH of blood
7.35 - 7.45 pH
Why is blood red?
O2 saturation (more O2 more bright) and presence of iron.
Best site for blood withdrawal
Medial cubital vein
2 components of blood
1. Blood plasma 55%
2. Formed elements. 44%
Components of blood plasma
1.5% other solutes
From hepatocytes: albumins, globulins and fibrinogen
From plasma cells: immunoglobulins and antibodies.
Part of formed elements of blood , about 1% of total blood volume.
Composed of WBC and platelets
Formed elements of blood
About 45% of total blood volume
Made of cells and cell fragments.
Three components of formed elements of blood
Red blood cells
White blood cells
Percentage if total blood volume occupied by RBC.
Six steps of hematopoeisis
1. Pluripotent stem cells
2. Specialized stem cells
3. Progenitor cell
5. Optional step
6. Developed formed elements.
Where does hematopoiesis occur?
In utero: yolk sac, then liver, spleen and thymus.
From third trimester on: red bone marrow in spongy bone.
What does red bone marrow produce?
RBC, WBC, platelets and lymphocytes.
Pluripotent stem cell
Mesenchymal cell that gives rise to all types of stem cells.
What types of stem cell arise from pluripotent cells?
Monocytes vs macrophage
Monocytes in the blood
Macrophage in the tissue
B lymphocyte vs plasma cell
A plasma cell is an active B cell
Jamie's mnemonic about the proportion of different WBC
60 20 8 2 oh never let my engine blow
2-4 % eosinophils
How much blood in an average adult?
5-6 L in males; 4-5 L in females.
Liquid-solid composition of an adult
Of the liquid, 2/3 intracellular fluid and 1/3 extracellular fluid
Of the ECF 80% interstitial fluid, 20% plasma.
Plasma (which itself is 55% blood volume) is composed of 91.5% H20, 7^ proteins and 1.5% other solutes.
What do myeloid stem cells develop into?
CFU-E --> reticulocyte --> RBC
CFU-Meg --> megakaryoblast --> platelet
--> eosinophilic myeloblast --> eosinophil
--> basophils myeloblast --> basophil
--> myeloblast --> neutrophil
--> monoblast --> monocyte/macrophage
What do lymphoid stem cells develop into?
T lymphoblast --> T lymphocyte
B Lymphoblast --> B lymphocyte --> plasma cell
NK lymphoblast --> natural killer cell
From which germ layer do pluripotent cells develop?
Derive from myeloid stem cells.
Cannot reproduce. Specialize into whatever blood cell they were programmed for.
CFU-E --> erythrocytes
CFU- Meg --> platelets
CFU-GM --> eosinophils, basophils, neutrophils, and monocytes.
Stage where blasts differentiate into actual blood cells
A hemopoietic growth factor that stimulates production of RBC
A hemopoietic growth factor that stimulates production of thrombocytes (platelets).
Red blood cell
Production of RBCs
Pigment contained in RBCs that binds O2. Gives blood its red colour.
Glycoproteins that act as local hormones. Stimulate proliferation of progenitor cells in RMB.
Include colony-stimulating factors (CSFs) and interleukins
Life span of the average RBC
How many RBCs are contained in blood?
Male: 5.4 million/microlitre
Female: 4.8 million/microlitre
What happens during the optional stage of blood cell development?
Reticulocyte ejects its nucleus --> Erythrocyte
Megakaryocyte shatters --> Platelets
How much of an RBC is composed of its cytosol?
33% by weight
How much hemoglobin does each RBC contain?
280 million, give or take
What is hemoglobin composed of?
Globin protein + 4 Heme
Protein portion of hemoglobin. Composed of 4 polypeptide chains (2 alpha helix, 2 beta sheet)
Non-protein portion of hemoglobin.
Composed of a ringlike pigment bound to each of the glob in protein chains (hence there are four hemes per hemoglobin).
At the centre of each ring is an iron ion, which can combine with one oxygen molecule.
What percentage of CO2 is transported by RBCs to the lungs?
70% is catalyzed by carbonicanhydrase into HCO3 (bicarbonate), which combines with amino acids in glob in and transported that way.
Remaining 7% dissolves in plasma
How do RBCs regulate blood flow and blood pressure?
Binding of nitric oxide
Why is carbon monoxide so deadly?
It binds competitively to heme group, with 200 times the affinity of O2.
Why do RBCs die after 120 days?
Wear and tear, and the inability to repair themselves.
What happens to ruptured RBCs?
Destroyed by fixed phagocytic macrophages in the spleen and liver
What happens to globin when RBCs are recycled?
Broken down into amino acids, which are recycled
What happens to heme when RBCs are destroyed?
Iron is removed.
Remaining heme is covered to biliverdin (green) and then to bilirubin (yellow-orange).
Bilirubin enters blood and is transported to liver.
Bilirubin released into bile, then passed into the small and then the large intestines, where it is converted into urobilinogen.
Most urobilinogen is converted into stercobilin and pooped out.
Some urobilinogen is absorbed into the blood, taken to the kidneys, converted to urobilin and peed out.
What happens to Fe+ when RBCs are destroyed?
Fe+ attaches to transferrin, which transports it to the liver, muscle and/or spleen, where it attaches to ferritin for storage.
When needed, it attaches again to transferrin, which transports it to RBM, where it meets up with globin, B12 and erythropoetin, and new RBCs are created.
A plasma protein which binds to and transports iron
An iron storage protein found in muscles, the liver, and the spleen
What heme converts into at the beginning of the recycling process.
What biliverdin converts into.
Travels through blood to liver, where it is released into bile, and passed into the small and large intestines.
What bilirubin gets converted into in the large intestine. Some gets absorbed into blood, some continues through intestine.
What urobilinogen gets converted into if it goes to the kidneys.
Excreted in urine
What urobilinogen is converted into in the large intestine before being excreted in feces.
How is the rate of erythropoesis measured?
Stages of erythropoesis.
Kidneys secrete erythropoeitin, which travels to RBM
In RBM, proerythroblast begins to synthesize hemoglobin.
Ejects nucleus, becomes reticulocyte.
Passes into blood stream. Within 1-10 days matures into RBC.
What determines rate of erythropoesis?
The amount of oxygen delivered to tissues.
Negative feedback system.
Low levels of cellular oxygen.
Too much CO2. Goes hand in hand with hypoxia.
White blood cells. Produced in RBM
Major Histocompatibility Antigens
Proteins on the PM of all nucleated cells that identifies the cell as "self".
Unique for each person.
Most numerous WBC. 60-70%
Phagocytosis of bacteria
Contains enzymes oxidants, lysosomes, defensins.
2-4% of all WBC
Red/orange acidic stain
Antihistamine, destroyer of parasitic worms and Ab-Ag complexes.
0.5-1% of WBC
Blue-purple basic stain
Releases serotonin, heparin and histamines to increase inflammation in allergic responses.
3-8% of all WBC
Called macrophage in tissues, monocyte in blood.
Main role is phagocytosis of dead cells and debris.
Fixed v wandering
20-25% of WBCs
T cells, B cells, Natural Killer cells
A type of lymphocyte
Attacks cancer, foreign and viral invaders.
A form of lymphocyte
Develop into plasma cells, which secrete antibodies.
Natural killer (NK) cell
A type of lymphocyte.
Destroys cancer and infectious microbes.
Ratio of RBC:WBC
What happens to the various WBCs after they leave the bloodstream?
Granular leukocytes and monocytes never return.
Lymphocytes circulate continually. (Only 2% in circulation at any given time). The rest are in skin, lungs, lymph nodes and spleen).
AKA diapedesis or pavementing
How WBC's leave the bloodstream. They roll along endothelium, stick to it, and squeeze between endothelial cells.
Adhesion molecules involved with WBC emigration
Selectins -- on endothelial cells
Integrins -- on WBC
Eating/engulfing another cell or microbe.
Performed by neutrophils and macrophages.
The process by which chemicals released by toxins or damaged tissue attract phagocytes
Normal, protective increase in the number of WBC.
Stressors can include microbes, strenuous exercise, anaesthesia and surgery.
When WBC count falls beneath 5000/microlitre
Stages of Phagocytosis
1. microbe adheres to phagocyte
2. phagocyte forms pseudopod that eventually engulfs the particle
3. phagocytic vesicle fused with a lysosome (=> phagolysosome)
4. Microbe is killed and digested by lysosomal enzymes, leaving residual body.
5. Indigestible and residual material exocytosed
Cancer of the WBCs
WBC death, due to trauma, disease or chemicals
Differential WBC Count
A count of each of the five types of WBC to determine specific infection, inflammation, allergic reaction and/or response to drugs or therapy.
Complete Cell Count
Ordered usually as part of a chemistry panel to determine levels of each cell in the blood to help with diagnosis
Not actual cells; fragments of megakaryocyte
Life span 5-9 days
Function primarily in plug formation and release of chemicals to assist in blood clot formation
What are the life spans of the various blood cells?
RBC 120 days
Platelets 5-9 days
WBC -- sometimes a few hours, up to several months or years
Precursor cell for platelets
Turns into megakaryocyte, which
splinters into 2000-3000 platelets
Hormone produced by the liver that stimulates the production of platelets
A sequence of responses that stops bleeding
1. vascular spasm
2. platelet plug formation
3. blood clotting (coagulation)
The loss of a large amount of blood
Clotting in an undamaged vessel. Usually self-dissolves
Broken off piece of thrombus that travels through blood stream. Can lodge in small arteries.
Contraction in smooth muscle in arteries and/or arterioles.
Immediate, autonomic nervous system response
Reduces blood loss during which time other hemostatic mechanism go into operation.
Probably caused by damage to smooth muscle, substances released by activated platelets, and/or pain receptor reflexes
Platelet plug formation
Postive Feedback Reaction
1. Platelet adhesion. Platelets float by and stick to damaged blood vessels (exposed collagen fibres)
2. Platelet Release Reaction. As adhesion platelets become actives, they "liberate their contents", which attracts other platelets. Liberated ADP and thromboxane A2 activate nearby platelets. Thromboxane A2 and serotonin also cause vasoconstriction.
3. Platelet Aggregation. Platelets collect and stick together.
4. Platelet Plug Formation. Initially loose but tightens when reinforced by fibrin threads formed during clotting.
A positive feedback reaction that turns a soluble protein into an insoluble protein.
Outside of the blood vessel, blood thickens into:
Serum (liquid blood plasma minus clotting proteins), and
Clot (gel, consisting of a network of insoluble protein fibres called fibrin and formed elements of blood trapped in fibres)
Clotting process. Involves factors derived outside blood.
Broken tissue releases Tissue Factor (ask thromboplastin, aka Factor 3)
TF + calcium = activates Factor X
Activated Factor X + Ca2 + Factor V => Prothrombinase
3 Phrases of Clotting
1 Prothrombinase formation (intrinsic and extrinsic pathways)
2. Prothrombinase converts prothrombin into thrombin
3. Thrombin converts fibrinogen into fibrin.
All factors involved are found within the blood
Damaged platelets and endothelium release chemicals that activate Factor XII --> Factor XII and Ca2 activate Factor X
Also, released platelet phospholipids plus Ca2 will also activate Factor X.
Activated Factor X + Ca2 + Factor V => Prothrombinase
Prothrombin (in presence of Ca2) converted via prothrombinase to thrombin (enzyme)
Thrombin converts fribrinogen to fibrin
Factor XIII plus thrombin --> activated Factor XIII, which strengthens fibrin threads via clot retraction.
In extrinsic pathway
Also called Tissue Factor
With Ca2, activates Factor X
Originates in Liver
In intrinsic and extrinsic pathways.
With Ca2 and Factor 5 --> Prothrombinase
From liver and platelets
In extrinsic and extrinsic pathways
With Ca2 and Factor 10 --> Prothrombinase
An active enzyme. In common pathway.
With Ca2, converts Prothrombin into thrombin
Plasma protein formed by liver that is converted into thrombin (by prothrombinase with Ca2)
An enzyme that activates Factor 13, and converts Fibrinogen to Fibrin.
From liver and platelets
When activated by Thrombin, strengthens fibrin threads (clot retraction)
Role of Vitamin K in blood clots
Not directly involved. Produces clotting factors.
Dissolves small unnecessary clots after damage has been repaired. By process of fibrinolysis
Inactive plasma protein incorporated into a blood clot. When activated into plasmin (aka fibrinolysin) which dissolves the clot.
Anticoagulant. Blocks Vitamin K thus prevents creation of clotting factors
Blocks thrombin formation
Produced by mast cells and basophils; helps activity of antithrombin
Activated Protein C (APC)
Blocks clotting factors and enhances plasminogen activator activities
Synthetic clot dissolvers
Tissue plasminogen activator (TPA)
Thrombolytic agent. Activates plasmin.
Thrombolytic agent. Produced by streptococcus bacteria. Helps dissolve clots.
Thrombolytic agent. Inhibits vasoconstriction and prevents platelet aggregation by blocking Thromboxane A2
Reduced O2 carrying capacity of the blood.
Characterized by fatigue, cold intolerance, pale skin.
Iron Deficiency anemia
Caused by inadequate absorption or intake of iron, or excessive iron loss, or increased requirement.
Most common form of anemia.
Due to inadequate B12 or folic acid intake.
RBM produce large, abnormal RBC.
Inadequate hemopoiesis due to inadequate absorption of B12, because of reduced production of intrinsic factor in stomach.
Due to excessive loss of RBC.
RBC plasma membrane ruptures prematurely.
May result from inherited disease, parasites, toxins or antibodies.
Hemoglobin release may damage kidneys.
Autosomal recessive disorder. Primarily in Mediterranean populations.
Deficient synthesis of hemoglobin -- no or reduced synthesis of polypeptide globin.
RBCs pale, short-lived, small.
Sickle Cell disease
Autosomal recessive. Creates abnormal hemoglobin Hb-S
Hb-S forms stiff, long, rodlike structures that bend RBC into sickle shape. RBCs rupture easily.
Carriers more resistant to malaria because altered permeability to potassium.
Sex linked recessive disorder
Deficiency in clotting due to deficiency of various blood clotting factors.
A group of WBC cancers in which abnormal WBCs multiply uncontrollably.
Reduced o2 transport, increased infection, abnormal clotting.
Too much iron stored or absorbed.
Primary or secondary.
Normal absorption 10%; hemochromatosis 30%
Symptoms: arthritis, liver disease, pancreatic or heart damage, abnormal pigmentation of skin (grey/bronze)
Abnormal yellowish discolouration or sclera of eyes, skin and mucous membranes.
Caused by excessive production of bilirubin
Abnormal bilirubin processing by liver
Due to blockage of bile drainage by gallstones or cancer or bowel or pancreas.
Antigen chemical markers
Glycoproteins and glycolipids
Present on surface of RBC
Antibodies contained on blood that react with A and B antigens.
Anti-a and anti-b antibodies
A. A antigen. Anti-b antibodies
B. B antigen. Anti-a antibodies
AB. Both antigens. No antibodies.
O. No antigens. Both antibodies.
ABO universal recipient
ABO universal donor
Antigen-antibody response. Blood cells clump together and get eaten by macrophages.
Results from incompatible blood transfusion.
Rh blood group
Rh another antigen on plasma membrane.
Normally no anti-Rh antibodies. Unless Rh- receives Rh+ blood, in which case antibodies produced and ready for next Rh+ influx. In which case agglutination and hemolysis.
Hemolytic disease of the newborn (HDN)
Rh- mother. Rh+ baby
If baby blood gets in contact with mother's blood, mom creates anti-Rh antibody which will be relevant for second pregnancy.
If second baby Rh+, agglutination and hemolysis in fetus.
Reduced oxygen carrying capacity of blood.
Iron deficiency anemia
Inadequate iron absorption,
excessive iron loss,
increased iron requirement,
inadequate iron intake
Insufficient intake of B12 and:or folic acid
Large, abnormal RBCs
Insufficient B12 absorption
Results from inability to produce intrinsic factor in stomach --> insufficient hemopoiesis
Excessive loss of RBCs
RBC membranes rupture prematurely
Inherited defect, parasites, toxins, antibodies
Release hemoglobin may damage kidneys
Autosomal recessive anemia
Deficient synthesis of hemoglobin
RBCs pale and short-lived
Destruction of red bone marrow
Toxins, gamma radiation, medications
Sickle cell disease
Abnormal hemoglobin bends RBC when giving up oxygen --> cell ruptures
Inherited deficiency of clotting
Sex linked recessive
Cancer of RBM
Body absorbs and stores to much iron
Primary (inherited) or secondary
Normal absorption 10%. Hemochromatosis up to 30%
Due to excessive production of bilirubin
Due to abnormal processing of bilirubin by liver