Blood Cells Immunity Blood Coags - Exam 2

Question 1

Reb blood cells aka __ carry __, bearing __ to the tissues

Answer 1

erythrocytes; hemoglobin; O2

Question 2

RBC’s contains ___, which catalyze what reaction

Answer 2

carbonic anhydrase

CO₂ + H₂O ➡ H₂CO₃

Question 2

biconcave disc of RBC’s allow them to

Answer 2

travel through blood capillaries with ease

Question 2

mature RBC’s lack

Answer 2

nucleus & mitochondria, thus they lack the power for cell division and rely on glucose for generating ATP

Question 3

eyrothropoesis

Answer 3

formation of RBC’s

Question 4

RBC count in men

Answer 4

5,200,000 mm³ +/- 300,000

Question 5

RBC count in women

Answer 5

4,700,000 mm³ +/- 300,000

Question 6

RBC counts can be increased at __ altitudes

Answer 6

higher

Question 7

MCV
MCH
MCHC

Answer 7

mean cell volume
mean cell hgb
mean cell hgb conc

Question 8

normal hgb concentration __ g per __ mL of packed cells

Answer 8

34 g per 100 mL

Question 9

normal hematocrit

Answer 9

40-45%

“packed cell volume”

Question 10

normal hgb

Answer 10

14-15g per 100 mL of blood

Question 11

O₂ carrying capacity is

Answer 11

1.34 mL/g Hgb, or 19-20 mL O₂/100 mL of blood

Question 12

hemoglobin structural unit:

Answer 12

• The predominant form in adults is Hgb A, with 2 ⍺ and 2 β chains
• each globin chain is associated with one heme group containing one atom of iron
• each of the four iron atoms can bind loosely with one molecule (2 atoms) of oxygen
• thus each Hgb molecule can transport 8 oxygen atoms

Question 13

bone marrow has what specific cell

Answer 13

PHSC (pluripotent hematopoietic stem cell)

Question 14

red bone marrow produces

Answer 14

2.5 million RBCs per sec

Question 15

regulation of erythropoiesis

Answer 15

• process stimulated by erythropoietin (EPO)
• from the kidneys that respond to low blood O₂ levels
• process takes about 3 days

Question 16

erythrocytes can be broken down into

Answer 16

heme and globin

• iron and heme can be recycled back to the body or it can be eliminated
• bilirubin forms from the breakdown of erythrocytes and travels to the liver and is then converted to bile can be absorbed by the small intestine and then can be eliminated as feces
• bile from the liver can also be recycled back to the kidneys and excreted as urine

Question 17

if there is too much erythrocyte break down

Answer 17

spleen can become enlarged

Question 18

factors that decrease oxygenation

Answer 18

1. low blood volume
2. anemia
3. low Hgb
4. poor blood flow
5. pulmonary disease

this tells kidney to make erythropoietin, negative feeb-back loop

Question 19

EPO

Answer 19

• circulating hormone
• necessary for erythropoiesis in response to hypoxia
• 〜90% made in the kidney
• cells of origin not established

Question 20

response to hypoxia

Answer 20

• minutes to hours ↑ erythropoietin
• new circulating reticulocytes 〜 3 days
• EPO → drives production of proerythroblasts from HSCs, accelerates their maturation into RBCs
• can increase RBC production up to 10-fold
• EPO remains high until normal tissue oxygenation is restored

Question 21

anemia

Answer 21

• reduced hgb in blood
• acute or chronic
• after hemorrhage: fluid volume restored in 1-3 days, RBC concentration restored in 3-6 weeks

Question 22

Vitamin B12 & folic acid

Answer 22

• rapid, large-scale cellular proliferation requires optimal nutrition
• cell proliferation requires DNA replication
• both are needed to make thymidine triphosphate (thus, DNA)
• abnormal DNA replication causes failure of nuclear maturation and cell division → large irregular fragile “macrocytes”

Question 23

pernicious anemia

Answer 23

- failure to absorb vitamin B12 - atrophic gastric mucosa: failure to produce intrinsic factor (intrinsic factor typically binds to vitamin B12) → protects it from digestion, binds to receptors in the ileum, mediates transport by pinocytosis - vitamin B12 - stored in the liver, released as needed, thus normal stored are adequate for 3 - 4 years

Question 24

folic acid present in

Answer 24

green vegetables, some fruits, and meats

Question 25

folic acid deficiency

Answer 25

- destroyed during cooking - subject to dietary deficiencies - may also be deficient in cases of intestinal malabsorption - maturation failure may reflect combined vitamin B12 and folate deficiency

Question 26

circulatory effects of anemia

Answer 26

- decreased viscosity - decreased O₂ (carrying capacity) → increases CO - markedly decreased exercise capacity

Question 27

polycythemia

Answer 27

- secondary to RBC count ↑ - chronic hypoxemia (heart or lung dx) - physiologic polycythemia: living at 14 to 17 thousand feet higher, markedly enhanced exercise capacity at altitude

Question 28

polycythemia vera

Answer 28

- clonal abnormality causing excessive proliferation - usually all lineages - 7 - 8 million RBCs, Hct 60-70% - hyperviscosity up to 3-fold from normal

Question 29

polycythemia & circulation

Answer 29

- increased viscosity decreases venous return - increased blood volume increases venous return - 2/3 normotensive, 1/3 hypertensive - the subpapillary venous plexus under the skin becomes engorged with slow-moving, de-saturated blood, producing a ruddy complexion with a bluish tint to the skin

Question 30

compensatory polycythemia

Answer 30

- sustained hypoxia can result in red cell mass above the usual normal range - some of the causes include: prolonged stay at high altitude, lung dx, HF

Question 31

first line of defense

Answer 31

mechanical barriers (skin & mucous membranes)

Question 32

pathogen enters the body

Answer 32

Second line of defense: - chemical barriers (enzymes, pH, salt, interferons, defenses, collectins, complement) - natural killer cells - inflammation - phagocytosis - fever Third line of defense: - cellular immune response - humoral immune response

Question 33

1st and 2nd line of defense combined is also known as

Answer 33

non-specific immunity or inet

Question 34

type of WBCs

Answer 34

- polymorphonuclear neutrophils - eosinophils - basophils - monocytes - lymphocytes circulate in the blood and may enter the tissues

Question 35

WBC count

Answer 35

〜 7,000/ mm³ (almost a 1,000 fold fewer than RBCs) proportions - neutrophils 62% (1st) - eosinophils 2.3% - basophils 0.4% - monocytes 5.3% - lymphocytes 30% (2nd)

Question 36

myeloid stem cell lineage

Answer 36

- RBC - Granular leukocytes: eosinophil, basophil, neutrophil - monocyte - platelets

Question 37

lymphoid stell cell lineage

Answer 37

- B-cell - T-cell

Question 37

neutrophils are __ cells that can respond __ to infection

Answer 37

mature; immedatley

Question 37

monocytes mature in the __ to become __

Answer 37

tissues; macrophages

Question 38

both exhibit motility:

Answer 38

- diapedesis - ameboid motion - chemotaxis (chemoattractants: bacterla or tissue degradation products, complement fragments, other chemical mediators)

Question 39

phagocytosis

Answer 39

ingestion of particles - must distinguish foreign particles from host tissues *toll-like receptors (TLRs): sensors for innate immune response. Fc receptors are detectors for adaptive immune response *

Question 40

specialized macrophages

Answer 40

- skin, subcutaneous (histiocytes) - lymph nodes: ingest/sample particles arriving through lymph - alveolar macrophages: digest or entrap inhaled particles and microorganisms - kupffer cells: surveillance or the portal circulation - macrophages in the spleen and bone marrow: surveillance of the general circulation

Question 41

inflammation is driven by __ mediators and caharacterized by:

Answer 41

chemical heat, redness, swelling and pain

Question 42

physiologically, it involves:

Answer 42

- vasodilation and increased blood flow - increased capillary permeability - coagulation of interstitial fluids - accumulation of granulocytes and monocytes - swelling of tissue cells

Question 43

inflammatory mediators

Answer 43

histamine, bradykinin, serotonin, prostaglandins, complement products, clotting components, cytokines, lymphokines

Question 44

different type of cytokines

Answer 44

interleukin 1, TNF- alpha, interleukin 6, interleukin 2, intereferons (type I & II), chemokines, colony-stimulating factors

Question 45

neutrophilia

Answer 45

increase in neutrophil count - with intense inflammation, neutrophil can increase dramatically - results from mobilization of mature neutrophils form the bone marrow by inflammatory mediators

Question 46

formation of pus:

Answer 46

- is composed of dead bacteria and neutrophils, many dead macrophages, necrotic tissue that has been degraded by proteases, and tissue fluid, often in a cavity formed at the inflammatory site - over days or weeks it is absorbed into the surrounding tissue and lymph and disappears

Question 47

eosinophils

Answer 47

- are weak phagocytes and exhibit chemotaxis - particularly important in defense against parasites - can adhere to parasites and release substances that kill them (hydrolases, reactive oxygen species, major basic protein) - also accumulate in tissues affected by allergies, perhaps in response to eosinophil chemotactic factor from basophils (eosinophils may detoxify some products of basophils)

Question 48

basophils

Answer 48

- similar to mast cell adjacent in capillaries... both cell types release heparin - basophils and mast cells both release histamine, bradykinin, and serotonin - when IgE bound to receptors on their surface is cross-linked by its specific antigen, mast cells and basophils degranulate, releasing: histamine, bradykinin, serotonin, heparin, leukotrienes, and several lysosomal enzymes

Question 49

leukopenia

Answer 49

- low WBC count, usually the result of reduced production of cells by the bone marrow - it can allow clinically severe infections with organisms that are not usually pathogenic

Question 49

within __ days of bonemarrow shut down, mucous membrane __ or resp __ may occur

Answer 49

2; ulcer; infection

Question 50

causes of leukopenia

Answer 50

radiation, chemical toxins, some medicines in most cases marrow precursors can reconstitute normal blood cell counts with proper support

Question 51

leukemia

Answer 51

- uncontrolled production of abnormal WBCs d/t a genetic mutation - clonal, lineage-specific, often immature cells

Question 52

leukemias are:

Answer 52

- lymphocytic vs. myelogenous - acute vs. chronic (sometimes up to 10-20 yrs)

Question 53

leukemias with partially differentiated cells may be classified as

Answer 53

neutrophilic, eosinophilic, basophilic, monocytic leukemias

Question 54

clinical effects of leukemias

Answer 54

- growth of leukemic cells in abnormal sites - invasion of bone from the marrow, with pathologic fractures - eventually spreads to vascular and lymphatic "filters" such as the spleen, lymph nodes, liver, and other organs - replacement of normal bone marrow, resulting in infection, and bleeding - wasting b/c of metabolic demands

Question 55

innate immunity

Answer 55

- non-specific - 1st and 2nd line - inborn ability to resist damaging organisms and toxins: skin, gastric acids, tissue neutrophils, and macrophages, complement microbicidal and lytic chemicals in blood and blood cells

Question 56

acquired / adaptive (specific) immunity

Answer 56

humoral → circulating antibodies cellular → activated cells

Question 57

antibodies are __ cells that specifically target and destroy invading __ & toxins

Answer 57

activated; organisms very powerful: can neutralize 100,000 x the lethal dose of some toxins

Question 57

antigen

Answer 57

- a substance that can elicit an immune response - unique to each invading organism - usually proteins or large polysaccharides - most are large and have recurring molecular groups on their surface - the molecular structures that are specifically recognized in acquired immunity are called "epitopes"

Question 58

2 types of lymphocytes

Answer 58

T-cells and B-cells

Question 59

lymphocytes mediate __ immunity

Answer 59

acquired

Question 60

where do lymphocytes develop?

Answer 60

lymphoid tissues: tonsils, adenoids, peyer's patches(GI), lymph nodes, speen, thymus, marrow

Question 61

maturation of T cells in the thymus

Answer 61

- rapid expansion - each clone is specific for a single antigen - self-reactive clones are deleted (up to 90%) - migrate to peripheral lymphoid organs much of the above occurs just before and slightly after birth

Question 62

B cell development and proliferation in response to antigen

Answer 62

- initial growth and differentiation in the liver (fetal) and bone marrow (after birth) - migrate to the peripheral lymphoid organs - each clone is specific for a single antigen - clonal development provides an almost limitless antibody specificity - secreted antibodies destroy and neutralize molecules or organisms hearing their cognate antigen

Question 63

each B or T cell clone is specific for a single __ of a single __

Answer 63

epitope; antigen - the genes for B & T cell receptors have hundreds of "cassettes" that are used in varying combinations - permutations of these cassettes allow specificity for millions of distinct epitopes

Question 64

lymphocyte activation

Answer 64

- macrophages in lymphoid organs → ingest antigen and present antigenic peptides to "helper" T cells - secrete IL-1, other cytokines that promote lymphocyte growth and differentiation - Helper T cells produce additional cytokines that stimulate B and T cell proliferation and differentiation - both B & T cells require antigenic stimulation to proliferate

Question 65

B-cell activation and antibody production

Answer 65

- B cells bind to intact antigen - B cells proliferate (with T cell help), developing lymphoblasts and plasmablasts - can persist for many weeks, if antigenic stimulation persists

Question 66

Antibody/immunoglobulin: structure & sepcificity

Answer 66

- at least bivalent (2 antigen-binding sites) - each antibody has a steric configuration specific to its antigen - multiple prosthetic groups of each antigen interact with complementary structures of the antibody through: hydrophobic bonding, hydrogen bonding, ionic interactions, van der Waals forces

Question 67

antibody classes

Answer 67

IgM, IgG, IgA(breast milk), IgD(less than 1%), IgE immunoglobulins make up about 20% of all plasma proteins

Question 68

What's the earliest produced antibody?

Answer 68

IgM

Question 69

whats the most abundant antibody?

Answer 69

IgG (75% of all immunoglobulins) cross the placenta

Question 70

which immunoglobulin is involved in allergic reactions?

Answer 70

IgE

Question 71

antibodies: mechanisms of action

Answer 71

- precipitation: makes soluble antigens insoluble, aiding elimination - agglutination: links cell-bound antigens together, causing clumping - neutralization: masks dangerous parts of the pathogen (exp. exotoxins) - inflammation: triggers histamine release, increasing immune motility the 4 above all enhance opsonization & phagocytosis - complement: complement protein perforated the cell membrane (cell lysis)

Question 72

T cell activation (involvement of MHC proteins and antigen presentation)

Answer 72

- T cells only recognize antigen fragments that are presented by MHC molecules of antigen-presenting cells(APCs): macrophages, B lymphocytes, dendritic cells

Question 73

MHC molecules

Answer 73

- encoded by the major histocompatibility complex - MHC I - present to cytotoxic T cells (CD8) ** - MHC II - present to helper t cells (CD4) ** - antigen in the context of MHC is recognized by as many as 100,000 T cell receptors per cell

Question 74

Helper T cells (CD4)

Answer 74

- 〜75% of all T cells - regulate functions of other immunologic cells by producing cytokines: IL-2,3,4,5,6, GM-CSF, interferon-gamma - positive feedback for helper T cells - stimulation of cytotoxic T cells - stimulation of B cells - macrophage accumulation, activation, enhanced killing

Question 75

General steps for helper T cell activation:

Answer 75

- binds to cognate antigen presented by APC - rapid expansion of T helper (CD4) cells - T helper cells produce cytokines - drives expansion of both T helper (CD4) and cytotoxic (CD8) T cells - both types of cells also generate clonal memory T cells

Question 76

Immunologic tolerance

Answer 76

- host defense employs powerful destructive mechanisms - these must be directed at pathogens while protecting host tissues from damage ** - "Tolerance" in acquired immunity is achieved mainly by clonal selection of T cells in the thymus and B cells in the bone marrow → clones that bind host antigens with high affinity are induced to undergo apoptosis, and are deleted

Question 77

Cytotoxic T (CD8) cells

Answer 77

- virus-infected cells - cancer cells - transplanted organs and tissues

Question 77

failure of immunologic tolerance results in

Answer 77

autoimmunity - rheumatic fever: cross-reactivity with streptococcal antigens - post-streptococcal glomerulonephritis - myasthenia gravis: antibodies to ACh receptors - systemic lupus erythematosus: auto-immune to multiple tissues

Question 78

active immunity is exposed by

Answer 78

antigen infection with attenuated organisms

Question 79

passive immunity

Answer 79

infusing antibodies or activated T cells from an immune individual (breast milk)

Question 80

allergy and hypersensitivity

Answer 80

- T cell-mediated (delayed): poison ivy, nickel allergies. ** Usually cutaneous; can occur in lungs with airborne antigens - IgE mediated (immediate): In typical allergies, a single mast cell/basophil can bind 500,000 IgE molecules

Question 81

anaphylaxis

Answer 81

- systemic, potentially fatal - widespread vasodilation - increased capillary permeability, volume loss - leukotrienes → bronchospasm and wheezing - treatment: epinephrine and antihistamines

Question 82

Uticaria

Answer 82

- localized vasodilation and red flare - increased permeability and swelling "hives" - treatment: antihistamines

Question 82

hay fever

Answer 82

- histamine-mediated - vascular dilation in the nasal passages and sinuses (and eyes) - leakage of fluid - sneezing - treatment: anti-histamines, local corticosteroids

Question 83

asthma

Answer 83

- mediated by leukotrienes - sustained bronchospasm - treatment: B agonists, inhaled steroids, leukotriene receptor blockers, treat upper airway component

Question 84

transfusion RBC's

Answer 84

- packed red cells - increase O₂ carrying capacity - one unit increases hematocrit 〜3%

Question 85

transfusion platelets

Answer 85

- single donation or apheresis - one unit raises platelet count 6-8,000/mL - indication < 50,000/mL, prior to surgery or with active bleeding

Question 86

transfusion FFP

Answer 86

- single donation or apheresis - usually for coagulation deficiency - solvent/detergent plasma inactivates viruses

Question 87

transfusion cryoprecipitate

Answer 87

clotting factors

Question 88

Early transfusions

Answer 88

- red cell agglutination and lysis - severe transfusion reactions, often fatal - in other cases, well-tolerated and beneficial - led to the discovery of RBC antigens and the practice of cross0matching - > 30 common antigens, many rare ones

Question 89

the ABO system

Answer 89

- ** RBC surface antigens: glycolipids or glycoproteins - agglutinogens: surface antigens (A,B) genes: A, B, O (maternal, paternal alleles) →genotypes: OO, OA, OB, AA, BB, AB - agglutinins (immunoglobulins): anti-A, and anti-B: begin developing age 2-8 months, peak age 10 years. response to A and B antigens in foods, and bacteria; initial exposures are environmental

Question 90

transfusion reactions: agglutination

Answer 90

- RBC's agglutinate - plug small vessels - physical distortion, phagocytic attack → hemolysis - in some cases, immediate, complement-dependent hemolysis

Question 91

The Rh(rhesus) antigens

Answer 91

- requires prior exposure to incompatible blood - six common antigens ("Rh factors") C, D, E, c, d, e - D ("Rh positive") is prevalent (85% EA, 100% Africans) and particularly antigenic - C and E can also cause transfusion reactions, generally milder

Question 92

Hemolytic disease of the newborn (erythroblastosis fetalis)

Answer 92

- ABO incompatibility ( O mother and A/B fetus): unusual, most anti-A is IgM, does not cross - Rh incompatibility (RhD+ fetus and Rh- mother): erythroblastosis fetalis, maternal antibodies cross the placenta and cause agglutination and lysis of fetal erythrocytes fetal macrophages covert hgb to bilirubin → jaundice anemic at birth; continued hemolysis for 1-2 months may have permanent neurologic damage from the deposition of bilirubin in neural tissues ("kernicterus")

Question 93

Hemolytic disease of the newborn: treatment

Answer 93

- repetitive removal of Rh-positive blood, replacement with Rh-negative (400 mL exchange over 90 mins) - may be done several times over a few weeks - maternal antibodies disappear over 1-2 months so newborn's Rh positive cells cease to be a target

Question 94

incompatibility: transfusion reactions

Answer 94

- occurs because of mismatched blood - recipient antibodies react against donor antigens - either immediate or delayed agglutination and hemolysis - fever, chills, SOB; potentially shock, renal shutdown - macrophages produce bilirubin - with normal liver function, no jaundice unless > 400 mL blood hemolyzed in < 1 day

Question 95

acute renal failure after transfusion reaction

Answer 95

- products of hemolysis cause powerful renal vasoconstriction - immune-mediated circulatory shock - free hgb can leak through glomerular membranes into tubules → High quantities may block tubules - may require acute or even chronic hemodialysis

Question 96

autograft

Answer 96

graft obtained from same individual

Question 97

isograft

Answer 97

graft obtained from an identical twin

Question 98

graft acceptance/rejection

Answer 98

- autografts & isografts - obstacles are mechanical attachment and adequate blood supply - allografts - antigenic matching is important - xenografts - almost always rejected with tissue death 1 day to 5 weeks after grafting successful allografts: skin, heart, liver, kidney, lung, pancreas, bone marrow, lasting up to 15 years or more

Question 98

allograft

Answer 98

graft obtained from another individual/same speicies

Question 99

xenograft

Answer 99

graft obtained from an entirely different species

Question 100

rejection:

Answer 100

- hyperacute rejection - Days - acute rejection - weeks - chronic rejection - months to years rejection is mainly due to activated T cells (predominantly helper T cells)

Question 101

avoidance or suppression of rejection

Answer 101

tissue typing: - blood type - HLA (MHC) antigens: encoded by the MHC, seek the best match possible among the closest relative possible - immunosuppressive drugs

Question 102

immunosuppressive drugs

Answer 102

- glucocorticoids - suppress the growth of lymphoid cells; reduce the production of antibodies and activated T cells - drugs that are toxic for lymphocytes - exp. azathioprine - * T cell specific agents - anti-lymphocyte globulin, cyclosporin, FK506 (tacrolimus), mycophenolate transformative, preventing graft rejection while leaving much of the immune system intact

Question 103

immunosuppression: challenges

Answer 103

- overwhelming infection, particularly viral infection - reduced tumor surveillance and increased incidence of cancer

Question 104

hemostasis: prevention of blood loss

Answer 104

- vascular constriction - formation of a platelet plug - formation of a blood clot - healing of vascular damage +/- re-canalization

Question 104

vascular constriction

Answer 104

- myogenic spasm - local autocoid factors from damaged tissued and platelets - nervous reflexes - smaller vessels: thromboxane A₂ released by platelets

Question 105

platelets

Answer 105

- 〜300,000/mm³ - 1-4 micrometers discs - released by fragmentation of mogakaryotes - 150-300,000 per microliter - replaced every 10 days - half-life of 8 to 12 days

Question 106

platelet functions

Answer 106

- contractile compatibilities - actin, myosin, thrombasthenin - residual ER and Golgi: synthesize enzymes, prostaglandins, fibrin-stabilizing factor, PDGF, store Ca⁺ - mitochondrial / enzymes: produce ATP, ADP

Question 107

platelet membranes:

Answer 107

- surface glycoprotein: repels intact endothelium, adheres to injured endothelium and exposed collagen - membrane phospholipids: activate blood clotting

Question 108

formation of the platelet plug

Answer 108

- contact with damaged endothelium: assume irregular forms, contract and release granules - adhere to collagen and vWF - other platelets accumulate, adhere, and contract, form plug, initiate clotting - very low platelets → petechiae, bleeding gums

Question 109

clot formation and progression

Answer 109

- begins in 15-20 seconds in severe vascular trauma - occlusive clot within 3-6 minutes unless very large vascular defect - 20-60 mins: clot retraction - 1-2 weeks: invasion by fibroblasts, organization into fibrous tissue

Question 110

fibrin production

Answer 110

- thrombin (weak protease) cleaves four smaller peptides from fibrinogen → fibrin monomer → spontaneous polymerization - long fibers form clot reticulum - fibrin stabilizing factor: in plasma and released from platelets, activated by thrombin, covalent cross-linking of fibrin monomers and adjacent fibrin fibers

Question 111

clot extension

Answer 111

- thrombin is bound to platelets and trapped in the clot - can act on prothrombin to generate more thrombin (+ FB) - thrombin also produces more prothrombin activator by acting on other clotting factors - additional fibrin monomers and polymers are generated at the periphery of the clot

Question 111

clot retraction

Answer 111

- begins within 20-60 mins - fibrin binds to the damaged vessel wall - platelets bind to multiple fibrin fibers: contract via actin, myosin, thrombosthenin - clot tightens, expressing serum, and slowing the vascular defect

Question 112

extrinsic pathway

Answer 112

trauma to the vessel wall and adjacent tissues can be explosive, with clotting in < 15 seconds

Question 113

intrinsic pathway

Answer 113

trauma to the blood or exposure of the blood to endothelial collagen much slower, 1-6 mins

Question 114

both pathways involve

Answer 114

clotting factors - mostly inactive proteases that are activated in cascades

Question 115

tissue injury →

Answer 115

- tissue factor activates the extrinsic pathway - exposure of factor XII and platelets to collagen activates the intrinsic pathway

Question 116

prevention of clotting

Answer 116

- smoothness of the endothelial cells - mucopolysaccharide coating (glycocalyx) repels platelets and clotting factors - thrombomodulin bound to endothelium binds (competes for) thrombin - thrombin-thrombomodulin activates Protein C → inactivates factors V and VIII - negative feedback: fibrin fibers bind 85-90% of thrombin and localize it to the clot, antithrombin III combines with the remainder and inactivates it over 12-20 mins

Question 117

heparin

Answer 117

- physiologically, availability is limited - used therapeutically - highly negatively charged - binds anti-thrombin III and increases its effectiveness 100- to 1000-fold - heparin-antithrombin III removes free thrombin from the blood almost instantly - also removes XIIa, XIa, Xa, and Ira - mast cells, basophils particularly abundant in pericapillary regions of the liver and lung

Question 118

*** Effect of heparin-induced thrombosis? (HIT)

Answer 118

immune reaction against heparin that forms large formation of clots → Platelets get reduced in this process, so it causes thrombocytopenia

Question 119

clot lysis

Answer 119

- plasminogen is trapped in the clot - over several days, injured tissues release tissue plasminogen activator (tPA) - plasminogen is activated to plasmin, a protease resembling trypsin - plasmin digests fibrin fibers and several other clotting factors - often results in the reopening of repaired small blood vessel

Question 120

key events in hemostasis

Answer 120

1. severed vessel 2. platelets agglutinate 3. fibrin appears 4. fibrin clot forms 5. clot retraction occurs

Question 121

causes of excessive bleeding

Answer 121

- hepatocellular disease - vitamin k deficiency - hemophilia - low platelet count

Question 122

vitamin K

Answer 122

- produced in the intestine by bacteria - fat-soluble: malabsorption of fats can lead to deficiency - lack of bile production or delivery can cause fat malabsorption and vitamin k deficiency - in patients with liver or biliary disease, vitamin K can be injected 4-8 hrs before surgery

Question 123

vitamin K deficiency

Answer 123

- essential to carboxylate glutamic acid in five important clotting factors: prothrombin and factors VII, IX, X, and protein C - in this process, vitamin K is oxidized and inactivated - vitamin K epoxide reductase complex 1 (VKOR c1) reduces vitamin K and reactivates it

Question 124

Hemophilia A

Answer 124

- deficiency of factor VIII - 85% of hemophilia cases - 1/10,000 males

Question 125

Hemophilia B

Answer 125

- deficiency of factor IX - 15% of cases - about 1/60,000 males

Question 126

both hemophilia's

Answer 126

- both impair intrinsic pathway activation - both genes on the X chromosome (males only get 1 copy) - clinically: bleeding after minor trauma

Question 127

Factor VIII deficiency

Answer 127

- factor VIII has two components - large & small - deficiency of the small component causes hemophilia A → treat bleeding with factor VIII replacement - deficiency of the large component causes von Willebrand disease (resembles decreased platelet function)

Question 128

throbocytopenia

Answer 128

- low number of platelets - bleeding from small venules or capillaries - petechiae, thrombocytopenic purpura - often idiopathic: < 50,000 = modest bleeding, < 10,000 = life-threatening - treated with platelet infusions → effective for 1-4 days each time

Question 129

Thrombus

Answer 129

- an abnormal clot is a thrombus, when it floats its an embolus - caused by: endothelial roughening (exp. atherosclerosis), slow flow (exp. prolonged air travel) - treatment: tPA, embolectomy

Question 130

pulmonary embolus

Answer 130

- usually from deep leg veins - part of the thrombus disengages 〜10% of the time - occludes pulmonary arteries - potentially fatal - tPA can be life-saving

Question 131

clinical useful anticoagulants: heparin

Answer 131

- binds, and potentiates antithrombin III - works rapidly, generally used acuteley

Question 132

clinical useful anticoagulants: Coumadins

Answer 132

- inhibit VKOR c1 - deplete active vitamin K → deplete active prothrombin, factors VII, IX, X - slower acting (days); used chronically

Question 133

clinical useful anticoagulants: In vitro anti-coagulation

Answer 133

- siliconized containers prevent activation of factor VII and platelets - heparin - used in blood collection, heart-lung and kidney machines - calcium chelators (citrate, EDTA) used in blood collection, blood storage

Question 134

prothrombin time

Answer 134

- add excess calcium and tissue factor to oxylated blood, measure time to clot - assesses extrinsic and common pathways ** - usually about 12 seconds - tissue factor batches have to be standardized (activity expressed as "international sensitivity index (ISI)"