Flashcards in Physiology - Exam 1, Deck #3 Deck (107):
How is blood maintained?
-Its composition and volume are maintained within narrow limits by homeostatic mechanisms = CONSTANT;
-Despite additions/losses of water and metabolic/nonmetabolic substances
What is Blood Volume?
-The sum of the volume of cells and plasma in the circulatory system;
-Ordinarily plasma volume and blood volume are determined separately
What is the equation for determining Plasma Volume?
-FICK equation = [C1 x V1 = C2 x V2];
1. Dye dilution technique –TR-1824, Evans Blue Dye;
2. Radioisotope dilution technique- RI138SA
What is the process for using Evan’s Blue Dye/Radioisotope for PV?
1. Injected concentrated dye into the circulatory system;
2. Allow enough time for it to mix thoroughly and sample it;
3. Determine concentration of the dye and determined the dilution factor;
4. PV is determined by the FICK equation
What is the composition of Blood when centrifuged?
1. Plasma on top;
2. Buffy coat between = Platelets and WBC
3. Formed elements on the bottom = RBCs
What is the Cell Volume by % Hematocrit?
*Cellular portion of the blood;
How is Blood Volume determined?
BV = [(PVx100)/100-H] x 100;
-Avg blood volume = 5.5 liters = 9-10 pints
What are the factors that vary blood volume?
7. Body Position
8. Degree of Recent Exercise
What is the composition of Blood Plasma (Fluid blood)?
**Plasma = 55% of blood volume
1. H2O = 92%
2. Solids = 8%
-Ions =Na+, Ca++, K+, Mg++, Cl-, HCO3-, PO4--- ,SO4—
-Proteins = 6-8grams / 100 mls of blood = serum albumin, serum globulin, fibrinogen
What happens when Plasma is resolved?
-Can be resolved into SERUM and the FIBRIN CLOT
1. Albumin = 55% of total plasma proteins – COP
2. Globulins = 44.8% of total plasma proteins
-Gamma = Immunoglobulin – circulating antibodies which play a role in the immune response
3. Fibrinogen = 0.2% - substrate which will be converted into the blood clot
Where are the Plasma proteins made?
-Globulins (except immunoglobulins), albumin, and fibrinogen – synthesized in the liver;
-Immunoglobulins – synthesized by lymphocytes and plasma cells of the REC
What are the functions of the plasma proteins?
-Exert colloidal osmotic pressure on tissue fluids;
-Amphoteric character – aid in regulation of pH;
-Fibrinogen is the substrate of the blood clot;
-Immunoglobulins are antibodies;
-Source of nutrition during starvation
What is the concentration of blood glucose?
-Normal range – 70-140 mg/dl;
-Replenished from absorption and liver glycogen;
-Under hormonal control from insulin, glucagon, and epinephrine
What are the NON-PRO Nitrogen Substances in Plasma?
2. Free Amino Acids;
3. Uric Acid;
end product of protein catabolism in man
Free Amino Acids
transported throughout the body for cellular protein synthesis
end product of purine catabolism in man; elevated uric acid concentration in gout and nephritis
*End product of muscle phosphocreatine catabolism;
-Plasma creatinine levels are often used clinically as an index of kidney function
-Since its secretion closely matches the GFR, an **abnormal decrease in GFR causes the plasma creatinine concentration to rise
What are the Blood Lipids?
1. Neutral Fats;
- transported as chylomicrons which are elevated during intestinal fat absorption
Transport and utilization of fats;
Core of nonpolar triglycerides and cholesterol esters;
-Coated by proteins (apolipoproteins), phospholipids, and some free cholesterol
-Needed in membranes and steroid hormones, excess → ATHEROSCLEROSIS;
-Sources are animal fats and endogenously produced in the liver;
-People with dangerously high LDL cholesterol often take drugs called STATINS = inhibit the enzyme HMG-coenzyme A reductase which catalyzes the rate limiting step in cholesterol synthesis in the liver;
-Lower intracellular cholesterol stimulates the production of LDL receptors in the liver allowing the liver to uptake more LDL cholesterol from the blood which decreases the amount of LDL cholesterol uptake into the endothelial cells of arteries
What are the types of Blood Cells?
1. Erythrocytes — RBCs — transport O2 and CO2;
2. Leukocytes — WBCs — immunological;
3. Thrombocytes — platelets — blood clotting
What are Erythrocytes?
-Transports hemoglobin which carries O2 and CO2;
-Shape – biconcave disc 8 x 2 µ;
-99% erythrocytes (mature)
-1% reticulocytes (immature)
-Normal concentration =
Men – 5.2 million/mm3;
Women — 4.8 million/mm3
Where do RBCs come from?
-in adults derived from cells called HEMOCYTOBLASTS in the red bone marrow;
-MATURE erythrocytes = lack a nucleus, mitochondria, the golgi apparatus, and the endoplasmic reticulum;
ATP is produced by glycolysis
-Reticulocytes are IMMATURE erythrocytes that pass from the bone marrow into capillaries
What is Eryhtropoiesis?
-Process of RBC formation;
-In bone marrow in adults;
-RBC forming tissue diminishes as we age;
-Tissue oxygenation (Hypoxia) is the basic regulator of erythropoiesis;;
-Stimuli - any condition that decreases the amount of O2 transported to tissues (anemia, life at high altitude)
What is the process of making more RBCs?
-ERYTHROPOIETIN , a glycoprotein hormone, stimulates the conversion of proerythroblasts to erythroblasts in bone marrow;
-Hypoxia in kidneys → release of an enzyme into the plasma that converts renal erythropoietin factor (plasma globulin) into erythropoietin;
-Procrit and EPO are commercially available erythropoietin
What are the cell stages of RBCs?
3. Reticulocyte - into capillaries;
4. Erythrocyte = Mature
What vitamins are needed for the formation of erythrocytes?
2. Folic Acid;
Role of B12
-Maturation factor - Vitamin B12;
-Required for the synthesis of DNA;
-Most common cause of maturation failure anemia is the failure to ABSORB Vitamin B12 from the Ileum
Often occurs in PERNICIOUS ANEMIA where an atrophic gastric mucosa fails to secrete normal quantities of INTRINSIC FACTOR WHICH combines with Vit. B12 and is necessary for absorption
Role of Folic Acid
-needed for DNA and RNA synthesis
How is Hemoglobin formed?
-Begins in erythroblasts and continues into reticulocyte stage;
1. Heme – from acetic acid and glycine in the mitochondria;
2. Globulin molecules – 4 = 2 alpha chains and 2 beta chains;
3. 4 heme molecules + 4 globulin molecules = hemoglobin
How much IRON is found within the body?
*Important in the formation of hemoglobin, myoglobin, and the cytochrome enzymes;
*Quantity of iron in the body = 4 gm;
-65% in hemoglobin
-4% in myoglobin
-1% in the cytochromes (ETS)
-15 -30% in the liver, principally as ferritin
How is Iron transported and stored?
1. Absorbed from SI and combines with transferrin(globulin) in blood plasma;
2. Excess iron→ liver cells (Iron + apoferritin → ferritin;
3. Low blood iron: ferritin → iron and apoferritin → plasma where it combines with transferrin;
4. Transferrin carries iron to bone marrow where it is used in hemoglobin synthesis
What are the daily losses of Iron?
Males = 0.6mg/day – mainly in the feces;
Females = 1.3 mg/day – feces and menstrual flow
What is the rate of destruction of RBCs?
-Average erythrocyte life span is 120 days;
-Cells rupture when squeezed in capillaries
1. Globulin is degraded by reticuloendothelial cells
2. Iron → transferrin
3. Heme → biliveridin → bilirubin
What is Anemia?
-Any pathological reduction in the number of RBC’s or in the amount of hemoglobin/ unit volume of blood;
-Normal Hb concentration
♂ = 15g%
♀ = 14g%;
-Minimum to give blood = 13.5g% — reason women can become so easily anemic
What are the common causes of Anemia?
1. Hemmorrhage = blood loss;
2. Iron deficiency anemia
3. Bone marrow aplasia = aplastic anemia: Common causes – drug poisoning, gamma ray radiation
4. Maturation failure- Lack of Vitamin B12 or folic acid
5. Hemolysis (rupture) – many causes: drug poisoning, hereditary diseases, snake bites
What are White Blood Cells?
-Leukocytes (circulating) and the reticuloendothelial system (stationary) combat infectious agents in two ways;
1. Phagocytosis or cell contact;
2. Form antibodies that destroy the invader;
-Leukocytes are the MOBILE units of the body
Where are the WBCs (leukocytes) made?
1. Bone marrow –granulocytes, monocytes – phagocytosis of invading organisms;
2. Lymph Nodes, spleen, thymus, tonsils – lymphocytes
= Lymphocytes – attach to specific invading organisms and destroy them or produce antibodies against the invading organism
What is the WBC concentration in the body?
-Average concentration = 7000/mm3;
-Normal composition with Wright’s stain
1. Granulocytes – granules in cytoplasm
2. Agranulocytes – Lack granules in cytoplasm
What are the Granulocytes?
-Granules in cytoplasm
1. Neutrophils – 62.0% of total
2. Eosinophils – 2.3%
3. Basophils – 0.4%
What are the Agranulocytes?
Lack granules in cytoplasm
1. Monocytes – 5.3%
2. Lymphocytes – 30% =
- Plasma cells – fewer → antibodies
- Memory cells- become plasma cells
** Cellular immunity
- Killer T cells
- Suppressor Tcells
- Helper T cells
What is DIAPEDESIS of WBCs?
-Squeeze through pores of endothelial cells of blood vessels (neutrophils and monocytes)
What is the Ameboid Motion of WBCs?
-In tissue spaces (neutrophils and macrophages);
-Macrophage – a large phagocytic cell in connective tissue that contributes to both specific and nonspecific immunity
What is Chemotaxis of WBCs?
-Movement towards or away from chemical substances in tissues (neutrophils and macrophages)
1. Bacterial toxins
2. Complement (complex of substances)
3. Degenerative products of inflamed tissues
4. Reaction products caused by plasma clotting in an inflamed area
What is Phagocytosis of WBCs?
-Neutrophils and macrophages;
-Whether or not phagocytosis occurs depends on several selective properties of the pathogen;
-More likely if:
1. The surface of the particle is rough
2. Cell has an electropositive charge; Healthy cells = electronegative charge
3. If the foreign material is combined with an OPSIONIN antibody
What is the Reticuloendothelial System (WBCs)?
-Distributed widely throughout the body;
-Most frequently includes two cell types =
1. Tissue Macrophages
2. Lymphocytic Cells
What are Tissue Macrophages?
-Derived mainly from MONOCYTES that have ENLARGED;
1. Divide in situ (on site) and form more macrophages — Form giant cell capsules around cell particles that can’t be digested- silvia dust, TB cell walls
2. Lymph nodes – capture foreign particles in lymph
3. Kupffer cells – liver sinuses – from hepatic portal blood (bacteria in GI mucosa through the portal blood passes through liver sinuses and phagocytized)
4. Spleen and bone marrow – general circulation
What are Lymphocytic Cells?
wander through tissues or are entrapped in special lymphoid tissues
What are Eosinophils?
-Remove toxic substances from tissues and release plasminogen; Increased with nematode infections
What are Basophils?
-Secrete HEPARIN (anticoagulant) into the blood stream;
-Move to tissues where they become mast cells
What are Lymphocytes?
-number of different types of cells;
-MULTIPOTENTIAL cells that are similar to the stem cells ;
-Play a special role in the process of immunity
What is Leukemia?
A disease characterized by the widespread pathological proliferation of one or more of the WBC forming tissues;
in granulocyte forming elements of BONE MARROW → anemia through crowding out of RBC forming tissue
-in LYMPHOCYTIC tissues which enlarge;
-secondary anemia when lymphocytes invade bone marrow
What are Thrombocytes?
*Blood Platelets =
-Formed in Bone marrow from megakaryocytes which represent 1% of the cells in the marrow;
-Megakaryocytes fragment and release platelets into circulation = cell fragments;
-Concentration – 200,000 – 300,000/ mm3
Play an important role in HEMOSTASIS
What is Hemostasis?
-Cessation of bleeding = Blood clotting;
-Breakage of the endothelial lining of a blood vessel exposes collagen proteins from the subendothelial connective tissue to the blood;
-Initiates three separate but overlapping hemostatic mechanisms:
2. Formation of a platelet plug
3. Production of a web of fibrin proteins that penetrates and surrounds the platelet plug
What are Blood Clots?
-Blood removed from the body CLOTS;
T-he complete gel of FIBRIN can be separated from the rest of the plasma ;
-[Plasma – fibrin clot] = serum (fluid);
-The fibrin clot is crosslinked and in the body it traps RBC and WBC
What factors affect Blood Clotting?
-There are over 30 substances found that affect blood clotting in blood and tissues;
1. Procoagulents – promote coagulation
2. Anticoagulants – inhibit coagulation;
-Whether or not blood clots depends on the BALANCE between these two groups of substances
What is the mechanism of Blood Clotting?
1. PROTHROMBIN ACTIVATOR is formed in response to:
-Rupture of a blood vessel or tissue (Extrinsic pathway);
-Damage to the blood (Intrinsic pathway or...
2. Prothrombin activator catalyzes the conversion of prothrombin into thrombin;
3. Thrombin acts as an enzyme to convert FIBRINOGEN INTO FIBRIN monomers that enmesh red blood cells and plasma to form the clot;
4. Fibrin monomers plus FIBRIN STABILIZING FACTOR → interwoven fibrin threads of the clot
What is Clotting Time?
-Appearance of the first strands of fibrin threads signals the onset of the clotting time of the blood;
**Normal = 8-9 minutes;
-Fibrin strands cross link = clot;
-The stabilization of the fibrin structure by cross links is the last stage of the clotting process and is due to the presence of FIBRIN STABILIZING FACTOR in plasma (FSF);
-Activation of FSF by thrombin which serves a dual role in the process:
1. Fibrinogen → fibrin monomer
2. Activate FSF
What are the Clotting Disorders?
1. Vit. K Def = inadequate formation of Prothrombin;
2. Hemophilia A = Sexual Recessive X (male dom.); Delayed formation of fibrin;
3. von Willebrand’s disease = autosomal; platelets can’t bind to collagen in connective tissues;
4. Hemophilia B = Sexual Recesssive X (male dom.); Delayed formation of fibrin
What are the major Anticoagulants?
1. Aspirin = Inhibits prostaglandin; Defective platelet release;
2. Coumarin = Inhibits Vit. K activation;
3. Heparin = Inhibits activity of thrombin;
5. Citrate = combines with Ca2+ and inhibits clotting factors (prothrombin activator requires Ca2+)
What is Fibrinolysis?
Lysis of blood clots = Maintains fluidity of the blood:
1. Eosinophils release plasminogen into the plasma;
2. Plasminogen is converted to PLASMIN by KALLIKREIN (enzyme);
3. Plasmin is an active proteolytic enzyme which digests fibrin = fibrinolysis;;
-Most tissues contain activators for plasminogen which are called FIBRINOKINASES;
-Liver can neutralize plasminogen activators and also secretes antiplasmin which competes with plasmin for fibrin
What is Immunity?
Ability of the body to resist all types of organisms or toxins that tend to damage the tissues and organs;
-Acquired = Humoral or Cellular
What is Innate Immunity?
1. Phagocytosis of bacteria and other invaders by WBC and reticuloendothelial system;
2. Destruction of organisms swallowed in the stomach by acid and digestive enzymes;
3. Resistacne of skin to invasion;
4. Chemical compounds in blood attached to foreign organisms/toxins and destroy them
*Makes humans resistant to some paralytic virus diseases of animals
What is Acquired or Adaptive Immunity?
Ability of the body to DEVELOP extremely powerful specific immunity against individual invading agents such as bacteria, viruses, toxins and foreign tissues from other humans;
-Occurs in a few days-weeks after exposure;
-Highly specific to each invader
-Two types = Humoral or Cellular
What is Humoral Immunity?
Development of circulating antibodies which are GLOBULIN molecules capable of attacking the invading agent
What is Cellular Immunity?
-Formation of large numbers of highly sensitized lymphocytes that are specific against foreign agents to which they attach and destroy
What causes an immune response?
Triggered by ANTIGENS;
-Acquired immunity is the product of the bodies LYMPHOID TISSUE — located in the lymph nodes, spleen, submucosa of GI and bone marrow
What are Anitgens?
Unique chemical compounds which elicit an immunological response in man;
Properties of antigens:
-Proteins, large polysaccharides, glycoproteins, or lipoproteins;
-Molecular weight of 8,000 or more;
-Regularly recurring prosthetic radicals on the surface of the large molecules
What are the the 2 types of Lymphocytes?
-T-lymphocytes = responsible for forming sensitized lymphocytes that provide CELLULAR immunity;
-B-lymphocytes = forms antibodies that provide HUMORAL; combat bacterial and some viral infections
Where do Lymphocytes come from in the embryo?
-Originate from LYMPHOCYTIC STEM CELLS in bone marrow;
-Eventual sensitized lymphocytes migrate to and are preprocessed in the THYMUS = T-lymphocytes;
-Antibody forming lymphocytes are pre-processed in the BONE MARROW = B-lymphocytes;
-T cells and B cells travel to and are localized in separate areas of the lymphoid tissue
What is the role of the Thymus Gland for Preprocessing the T-Lymph?
Occurs shortly before birth of the baby and a few months after birth;
-Beyond that = can remove thymus with NO effect on T-Lymphocytes;
-If removed several months before birth = No cellular immunity
What is the role of the Bone Marrow in mammals?
For processing of B-lymphocytes;
-B-lymphocytes preprocessed in the latter part of the fetal life
How are processed lymphocytes to the lymphoid tissue?
1. Thymus or bone marrow;
6. Lymphoid tissue where they STAY
What is the Clonal Selection Theory?
1. Lymphocytes inherit the ability to produce specific antibodies — Prior to antigen exposure, lymphocytes that can make the appropriate antibodies are already present in the body;
2. Antigens interact with antibody receptors on the lymphocyte surface — Antigen-anitbody interaction stimulates cell division and the development of lymphocyte clones that contain memory cells and plasma cells that secrete antibodies;
3. Subsequent exposure to the specific antigens produce a more efficient response — Exposure of lymphocyte clone to specific antigens results in greater and more rapid production of specific antibodies
What are Precursor Lymphocytes?
Hundreds of thousands of different types of precursor lymphocytes pre-exist in the lymph nodes for formation of many specific types of T-lymphocytes or B-lymphocytes
What is Primary Response of Lymphocytes?
-On 1st exposure to pathogen, there is latency of 5-10 days before specific antibodies are made = primary response;
-Antibody levels plateau after few days & decline after a few weeks
What is the Second Response of Lymphocytes?
-Subsequent exposure to same antigen causes secondary response;
-Antibody production is much more rapid & sustained
What is the Mechanism of Tolerance?
-Tolerance develops during the pre-processing of lymphocytes in the thymus (T) and bone marrow (B);
-If a strong antigen is injected into the fetus while lymphocytes are processed, no clones or lymphocytes in lymphoid tissue specific to the injected antigen will develop
What is an Autoimmune Disease?
Failure of the tolerance mechanism;
-Occurs more frequently with age;
-Usually results from destruction of some of the bodies tissues releasing antigens in to the circulatory system and activation the acquire immune system;
-Several common diseases:
1. Rheumatic fever —immunized against strep infection;
2. Glomerulonephritis (one type)
3. Myasthenia gravis
4. Lupus erythmatosus
How are antibodies formed in the plasma?
1. Antigen phagocytized by macrophages in the lymph tissue that transfer antigens to adjacent lymphocytes;
2. Lymphocytes for that antigen enlarge = LYMPHOBLASTS;
3. Some lymphoblasts differentiate to form 500 plasma cells for be lymphoblasts in the next 4 days;
4. Mature plasma cells then produce gamma globulin antibodies at a fast rate — 2000molcules/sec/plasma cell;
4. AB — lymph — blood;
5. Continues until death of the plasma cells
How are Memory Cells formed?
-Difference between primary and secondary response;
-Some of the lymphocytes formed by activation of a cone of B-lymphoctes form moderate numbers of new B-lymphocytes = memory cells;
-Added to the original lymphocytes of the clone and remain dormant until active by a new round of the same antigen ;
-Subsequent or second response will produce antibodies much quicker due to “memory"
What are Immunoglobulins?
-Antibodies are gamma globulins = Immunoglobulins;
-Composed of a combo of heavy and light polypeptide chains, typically 2 light and 2 heavy;
-Each heavy is paralleled by a light at one end — at least 2 pairs in each immunoglobulin;
-A designated end of each of the light and heavy chains = VARIABLE END; remainder is constant;
-Variable end is what determines the different antibody specificities
What are the Immunoglobulins?
1. IgG = Main antibodies in circulation; Increased after IMMUNIZATION; Secondary response;
2. IgA = Main antibody in EXTERNAL secretion; Saliva and mother’s milk (passed through breast feeding);
3. IgE = Allergic symptoms in immediate hypersensitivity rxns;
4. IgM = Antigen receptors on lymphocyte surface BEFORE immunization; Secreted during PRIMARY response;
5. IgD = Antigen receptors on lymphocyte surface BEFORE immunization; other unknown
What determines the specificity of Antibodies?
-Different AA residues in the variable portion of the light and heavy chains;
-Steric sites of the antibody will fit in the antigen;
-Most are BIVALENT = 2 rxn sites
What are the 4 mechanisms of action by Antibodies?
1. Agglutination - multiple antigentic agents are bound in a clump;
2. Precipitation — complex of voluble antigen and antibody becomes insoluble and precipitates;
3. Neutralization — antibody covers toxic sites of antigen;
4. Lysis — antibody attacks membrane of pathogen and ruptures
What is the Complement System?
-Cascading effect of 9 different enzymes (C1-9) found in the plasma and body fluids that provide the most protection against antigens;
-Enzymes are normally INACTIVE
What activates the Complement System?
1. Antibody and antigen interact on the constant portion of the antibody = enzyme activation;
2. Cascade begins and attack by:
-Opsonization — makes pathogen highly susceptible to phagocytosis;
-Chemotaxis — moves neutrophils/macrophages to antigen;
-Agglutination — enzymes change antigenic surface making pathogens bind;
-Neutralization of viruses — nonvirulent
What is the Anaphylactic System due to Antibody activation?
1. Antibody attaches to MAST (fixed) cells in tissues around blood vessels to basophils;
2. Antigen + Antibody attached to mast cell causes swelling and rupture = release HISTAMINE — causes the accumulation of fluid in interstitial compartment;
3. Immobilization of antigenic invader
What are Cytokines produced by activated T-cells?
-T-lymphocytes (and other macrophages) secrete polypeptides that are AUTOCRINE (regulate many aspects of the immune system) and are call CYTOKINES;
-Lymphokines = cytokines of lymphocytes;
-*INTERLEUKINS regulate the immune system
Proliferation/activation of T-lymphocytes
Proliferation of activated T-lymphocytes
Stimulates proliferation of bone marrow stem cells and mast cells
Proliferation of activated B cells;
-Promotes production of IgE antibodies;
-Increases activity of cytotoxic T cells
Induces activation of cytotoxic T cells;
-Promotes eosinophil differentiation and serves as chemokine for eosinophils;
Proliferation and activation of T and B lymphocytes
Granulocyte/Monocyte Colony-Stimulating Factor (GM-CSF)
Stimulates proliferation and differentiation of neutrophils, eosinophils, monocytes, and macrophages
Type A Blood
-Possesses Type A antigen;
-Produces antibodies against Type B antigen
Type B Blood
-Possesses Type B antigen;
-Produces antibodies against Type A antigen
Type AB Blood
-Possesses Type A and B antigens;
-DOES NOT produce any antibodies against any blood type of the ABO system;
Type O Blood
-DOES NOT possesses either A or B antigens on RBCs;
-Produces antibodies against BOTH A and B antigens;
Terminology of Blood Typing
-Antigens = Agglutinogens;
-Antibodies = Agglutinins
Caucasian Blood Types
-Type A – 41%
-Type B – 10%
-Type AB – 4%
-Type O – 45%