PNB EXAM 1: BLOOD
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Blood is considered what type of tissue?
what is the purpose of blood?
it's a transport medium that carries materials around the body thought our vascular system powered by the heart
blood's lifespan is how long?
What is hematocrit?
it is also known as packed cell volume and is the proportion of whole blood made up of blood cells
what is the difference between a male and female's hematocrit?
- hematocrit %
- males: 40 - 50%
- females: 36 - 44%
when put in a centrifuge, what happens to blood?
- it divides into three compoenets
- - plasma
- - buffy coat
- - erythrocytes
lies between the plasma and erythrocytes when put through the centrifuge. it represents the leukocytes
what does the packed cell volume refer to ?
the amount of red blood cells
what is the normal volume for hematocrit?
blood cells make up what three main components?
- - red blood cells
- - white blood cells
- - platelets
what is a erythrocyte ?
a red blood cell
what is a leukocyte?
white blood cells
is the fluid portion of blood which is made of more the 90 % of water. it contains proteins and other solutes
Blood plasma include which proteins?
- makes up 7%
- - Albumins
- - Globulins
- - Clotting proteins
- - regulatory proteins
blood plasma include what type of solutes?
- makes up 1%
- - Nutrients
- - Electrolytes
- - respiratory gases
- - wastes
- - regulatory substances
Blood Plasma Protein: Albumin
- - produced by the liver: as non-penetrating solutes, albumins exert osmotic pressure (“colloid osmotic pressure”) to maintain water balance between blood and tissues; also function as carriers and buffers.
- - allows exchange between blood and interstitial fluid at the capillary level
Blood Plasma Protein: Globulins
- - alpha and beta globulins (produced by liver) - act as transport proteins; and gamma globulins (produced by immune system) which function in immunity
- - include immune proteins such as antibodies
Blood Plasma Protein: Clotting proteins
- Fibrinogen; prothrombin
- - helps with blood clottingwhile circulating throughout the body they are in inactive form
Blood Plasma Protein: Regulatory proteins
consists of enzymes, pro-enzymes, and hormones such as insulin
transport lipids and some metal ions
transport iron ions and lipids in bloodstream
are antibodies that immobilize pathogens
Blood Plasma Solutes: Nutrients
- a energy source]
- - organic materials including glucose, amino acids, lipids
Blood Plasma Solutes: Electrolytes
- they help establish and maintain membrane potentials, maintain pH balance, and regulate osmosis
- - Cations including Na+, K+, Ca++, Mg++ ; and anions (Cl-, HCO3, phosphates, and sulfates).
Blood Plasma Solutes: Respiratory gases
include Oxygen, CO2, N2
Blood Plasma Solutes: Wastes
waste products are transported to the liver and kidneys where they can be removed from the blood
Blood Plasma Solutes: Regulatory substances
include hormones and other chemical signals
homeostasis pertaining to blood?
means keeping many of the constituents of blood plasma within narrow limits
- - small, biconcave disk
- - anuclear
- - lack organelles
Erythrocytes contain cytoskeletal proteins: give an example and its purpose.
- ex: spectrin
- - gives its biconcave shape and makes it quite flexible
why do erythrocytes have a biconcave shape?
- - transport: contains the same volume of hemoglobin with the most surface area - this facilitates oxygen transport
- - also plays a role in lamina flow (nice even flow of blood)
erythrocytes cannot do what?
divide or synthesis new erythrocytes
- - contains 4 globin chains (2 alpha chains, 2 beta chains)
- - each chains is complexed with an iron containing heme group
- - there 4 hemes in one hemoglobin
Each hemoglobin molecule can bind how many molecular oxygens?
Iron atom in heme is able to reversibly bind oxygen; thus allows blood to pick up oxygen in the lungs (forming oxyhemoglobin, which gives arterial blood its bright red color) and then releases this oxygen to the tissues, following the concentration gradients favoring diffusion.
what is a heme
- a nitrogen containing compound with an iron atom
- - the iron atom allows oxygen to reversibly bind
what are the three forms of hemoglobin?
- - oxyhemoglobin (HbO2)
- - deoxyhemoglobin = reduced hemoglobin
- - carbaminohemoglobin (HbCO2)
displaces oxygen from heme b/c it can bind more tightly (has a higher affinity)
- act on the mitochondria level and disrupt electron transport and oxygen transport
- - can also bind to the iron in heme and prevent it from carrying oxygen
process of forming blood
what is the stem cell that makes all blood cells?
hemocytoblast (blood stem cell)
hemocytoblast can create what two lines?
- - myeloid line
- - lymphoid line
consist of the myeloid stem cell which then creates red blood cells and white blood cells (other then lymphocytes)
consists of the lymphoid stem cell which creates lymphocytes. It divides into the B-lymphoblast and the T-lymphoblast which then turns in to B-lymphocyte and T-lymphocyte
occurs in red bone marrow and the formation of red blood cells (erythrocytes)
how do the stem cell hemocytoblast know that it needs to make more red blood cells in erythropoeisis?
by the chemical signal EPO
What are the factors needed in erythropoeisis?
- - Iron
- - Vitamin B12
- - folic acid
- 65% of body’s iron in Hb, rest stored inside cells of liver, spleen and bone marrow as protein-iron complexes (ferritin, hemosiderin). In blood, iron travels bound to transferrin.
- - for red blood cell formation
- - why? becuase iron is apart of heme - whithout iron you don't bond oxygen
erythropoeisis: vitamin B12
necessary for DNA synthesis (and therefore for cell division). Deficiency of this vitamin leads to pernicious anemia. Note: Intrinsic factor, a protein secreted by stomach, is necessary for dietary absorption of vitamin B12 - thus anemia can result from a lack of intrinsic factor.
erythropoeisis: folic acid
Necessary for DNA synthesis. (B vitamin deficiency leads to a specific anemia.)
the chemical signal that directs the development of the hemocytoblast into a red cell
what are the steps of erythropoeisis
- - hemocytoblast
- - progenitor cell
- - Day one: blast cell - proerythroblast
- - Day two: basophilic erythroblast
- - Day three: polychromatophilic erythroblast
- - Day four: normoblast
- - Day 5-7: Reticulocyte
- - mature red blood cell
why is there a huge nucleus in the erythroblast?
- b/c there is much DNA transcription and therefore translation and protein synthesis going on
- - cells with a nucleus are capable of mitosis
erythropoeisis: day 4 normoblast significance
at the end of the normoblast stage the nucleus will be ejected but still has some ribosomes
erythropoeisis: day 5-7 reticulocyte significance
- not capable of mitosis and still contain robosomes
- - can carry oxygen and some will enter the blood stream
- - at the end of the stage it loses its ribosomes and enters the circulation
Control of Erythropoeisis
- 1. stimulus = hypoxia (decreased O2 levels in blood) decreased RBC count, decreased availability of O2, increased tissue demands for O2
- 2. in response to the stimulus, the kidneys releases the protein hormone erythropoietin
- 3. EPO acts on bone marrow to enhance erythropoiesis
describe the catabolism of red blood cells
- 1. erythrocytes leave the bone marrow
- 2. they circulate in the bloodstream for 120 days
- 3. at the end of life the enter the spleen where it will metabolize the old red blood cells and recycle the heme components
- 4. the heme components travel to the liver. the iron portion of the heme will be stored in the liver for later use. the heme without iron will be turned into bilirubin which is them secreted in bile from the liver
- 5. erythrocytes membrane proteins and globin proteins are broken down into amino acids, some of which are used to make new erythrocytes
what does anemia mean?
it means not enough oxygen being delivered to tissues
what can cause anemia?
- - low red blood cell count (hematocrit will be lower than 45%)
- - low hemoglobin
- - abnormal hemoglobin
what are some anemias caused by abnormal hemoglobin
- - thalassemia B
- - sickle cell anemia
- - abnormal amounts of Hb (due to lack of adequate production of Beta chain)
- - red blood cells are microcytic (small) and hypochromic (pale)
where is Thalassemia B common?
- - in the Mediterranean region
- - portions of Africa
- - Asia
- - south pacific
- - India
Sickle Cell Anemia is more common where?
- - more common in people and their descendent from
- - tropical and subtropical regions where malaria is present
Sickle Cell anemia
- - single "wrong" animo acid results in abnormal HbS
- - abnormally shaped cells cannot move through bloodstream easily; thus hard to delieve O2 to tissues
- - red blood cells are fragile => hemolytic anemia (and more 02 deprivation)
Polycythemia: hematocrit levels
will be more than 45%
what is polycythemia
an increase in red blood cells
can be dues to things such as lead poisoning
secondary to high altitude or occurs because it is functional to the body rather then it being a mutation
what is blood doping and why is it a bad idea?
- artificial method: by taking an EPO stimulant or by taking out some of their blood, saving it, and using it when they need (for competition)
- natural method: by running at high altitudes
- However, by increasing the number of erythrocytes per measured volume of blood, blood doping increases the viscosity of the blood. Thus, the heart must work harder to pump this “thicker” more cellular blood. Eventually, temporary athletic success may be overshadowed by permanent cardiovascular damage that can even lead to death.
which of the leukocytes circulate throughout the body?
- - Neutrophils
- - Eosinphils
- - Basophils
- - lymphocytes
- - monocytes
what is the function of a leukocyte?
- body's defense mechanism for both non-specific and specific (immune) responses
how many types of white blood cells are there?
- - 5 circulate throughout the body while the last stays in the bone marrow
leukocytes are divided into what two categories?
- - granulocytes
- - agranulocytes
granulocytes consists of which leukocytes?
- - neutrophils
- - basophils
- - eosinophils
agranulocytes consists of which leukocytes?
- - monocytes
- - lymphocytes
- - megakaryocytes
- - Nucleus is multilobed (as many as five lobes)
- - Cytoplasm contains neutral or pale, distinct granules (when stained)
- - Phagocytize pathogens, especially bacteria
- - Release enzymes that target pathogens
- - Nucleus is bilobed
- - Cytoplasm contains reddish or pink-orange granules (when stained)
- - Phagocytize antigen-antibody complexes and allergens
- - Release chemical mediators to destroy parasitic worms
- - Nucleus is bilobed
- - Cytoplasm contains deep blue-violet granules (when stained)
Release histamine (vasodilator) and heparin (anticoagulant) during inflammatory or allergic reactions
- - Round or slightly indented nucleus (fills the cell in smaller lymphocytes)
- - Nucleus is usually darkly stained
- - Thin rim of cytoplasm surrounds nucleus
- - Attack pathogens and abnormal/infected cells
- - Coordinate immune cell activity
- - Produce antibodies
- - Kidney-shaped or C-shaped nucleus
- - Nucleus is generally pale staining
- - Abundant cytoplasm around nucleus
- - Can exit blood vessels and become macrophages
- - Phagocytize pathogens, cellular debris, dead cells
Do not circulate; produce platelets
process of making white blood cells
how do you stimulate leukopoeisis?
by colony stimulating factors: which determine whether the cell will go down the red blood cell path or the white blood cell path
platelets are regulated by what?
thromboprotein - signals the development of magakaryocytes which then produces fragments into platelets
platelets are essential for what function?
process which stops bleeding (blood flow)
name the three phases/stages of hemostasis
- - Vascular spasm
- - platelet plug formation
- - coagulation (formation of the clot)
hemostasis: vascular phase
- - damaged blood vessels constrict
- - the mechanism for this isn't really clear
- - can sometimes stop at this first phase if the vessel is small enough
hemostasis: platelet plug
- - simulus = damaged endothelium and exposure to collagen
- - platelets swell, form processes, become sticky, and adhere to collagen
- - degranulation: release of chemicals from platelets => platelet aggregation
describe the platelet plug feed back mechanism
- Degranulation => Platelet aggregation: Degranulation releases chemicals which attract more platelets => more degranulation => more platelets. Plug is quickly formed.
- - its positive feed back
chemicals favoring plug formations are?
- - von Willebrand factor
- - Serotonin
- - ADP
- - TxA2 (Thromboxane A2 - and eicosanoid)
- - clotting factors
chemicals limiting plug formation are?
- - PGI2 (Prostacyclin)
- - NC (nitric oxide)
Hemostasis: Coagulation Phase
- clot (thromnus) = fibrin polymer
- - clotting occurs locally around platelet plug
- - platelet factor (Pf) from activated platelets is an essential cofactor
- - many other factors/cofactors
Hemostasis: Coagulation consists of what pathways?
- - intrinsic pathway
- - extrinsic pathway
- - common pathway
- - intrinsic to blood: blood activates the pathway
- - factor XII activated by contact to collagen
- - intrinsic pathway canbe activated independent of contact activation andfactor XII
- requires tissue factor (from subendothelial cells in vessel wall). this factor is released when tissue becomes damaged
- two pathways both extrinsic and intrinsic converge at activation of factor X
which pathway is typically activated first ?
- the extrinsic pathway
- - which then triggersThrombin’s positive feedback effects on INTRINSIC pathway
what is a pro-coagulant
- - cleaves fibrinogen to fibrin
- - activates clotting factors XI, VIII, V, XIII
- - stimulated platelet activation
- - activates protein C, which inactivates clotting factor VIIIa and Va
clotting factor XI
- - activated by factor XIIIa; synthesized in the liver
clotting factor VIII
- - activated by thrombin; synthesized in megakaryocytes and endothelial cells
clotting factor V
- both intrinsic and extrinsic
- - activated by thrombin and synthesized in the liver
clotting factor XIII
- both intrinsic and extrinsic
- - activated by thrombin in presence of Ca2+; stabalizes fibrin clot by covalent cross-linking
Anticoagulants include which ?
- - anti-thrombin
- - heparin (mast cell)
- - heparan sulfate
- - thrombomodulin
- - fibribolytic system
Liver; weak anticoagulant;enhanced in presence of heparin
Liver’s Roles in Blood Clotting
- • Synthesis of bile salts; aids in absorption of fat/ vitamin K
- • Synthesis of clotting factors (which require vit. K)
- it itself helps prevent coagulation
- – Intact vessel endothelial cells
- – Low anticoagulant activity
Receptor that binds thrombinand activates Protein C, which INACTIVATES two clottingfactors
- used to break down the clot when its time
- - ex: tissue Plasminogen Activator(TPA)
is the contractile processes
- a normal body process that keeps naturally occurring blood clots from growing and causing problems
- - “clot buster” – Tissue Plasminogen Activator (TPA) – released by endothelial cells.
Disorders of Hemostasis
- – Clot forms
- – Breaks loose =embolus
- – May lodge in lungs(pulmonaryembolism)
is where both the extrinsic and intrinsic converge. It takes prothrombin and changes it into thrombin
thrombin's affect on fibrinogen?
thrombin act on FIBRINOGEN and turns it into fibrin which is the building block of the clot itself- - fibrin needs to be polymerized and stabilized; thrombin does not do this directly. rather thrombin activates factor XIII (13) which turns to XIIIa (activated) and now we have the polymer stabilize fibrin
how does thrombin reinforce the whole cascade shown in the slides?
thrombin reinforces the whole cascade. it has a positve feedback affect on the cascade. because of this we can say the even though the intrinsic pathway was not caused by exposure to collagen, it was still activated by thrombins positive feedback
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