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Patho II > Blood Cells Immunity Blood Coags - Exam 2 > Flashcards

Blood Cells Immunity Blood Coags - Exam 2 Flashcards

1
Q

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

A

erythrocytes; hemoglobin; O2

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2
Q

RBC’s contains ___, which catalyze what reaction

A

carbonic anhydrase

CO₂ + H₂O ➡ H₂CO₃

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2
Q

biconcave disc of RBC’s allow them to

A

travel through blood capillaries with ease

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2
Q

mature RBC’s lack

A

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

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3
Q

eyrothropoesis

A

formation of RBC’s

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4
Q

RBC count in men

A

5,200,000 mm³ +/- 300,000

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5
Q

RBC count in women

A

4,700,000 mm³ +/- 300,000

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6
Q

RBC counts can be increased at __ altitudes

A

higher

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7
Q

MCV
MCH
MCHC

A

mean cell volume
mean cell hgb
mean cell hgb conc

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8
Q

normal hgb concentration __ g per __ mL of packed cells

A

34 g per 100 mL

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9
Q

normal hematocrit

A

40-45%

“packed cell volume”

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10
Q

normal hgb

A

14-15g per 100 mL of blood

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11
Q

O₂ carrying capacity is

A

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

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12
Q

hemoglobin structural unit:

A
  • 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
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13
Q

bone marrow has what specific cell

A

PHSC (pluripotent hematopoietic stem cell)

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14
Q

red bone marrow produces

A

2.5 million RBCs per sec

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15
Q

regulation of erythropoiesis

A
  • process stimulated by erythropoietin (EPO)
  • from the kidneys that respond to low blood O₂ levels
  • process takes about 3 days
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16
Q

erythrocytes can be broken down into

A

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
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17
Q

if there is too much erythrocyte break down

A

spleen can become enlarged

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18
Q

factors that decrease oxygenation

A
  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

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19
Q

EPO

A
  • circulating hormone
  • necessary for erythropoiesis in response to hypoxia
  • 〜90% made in the kidney
  • cells of origin not established
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20
Q

response to hypoxia

A
  • 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
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21
Q

anemia

A
  • reduced hgb in blood
  • acute or chronic
  • after hemorrhage: fluid volume restored in 1-3 days, RBC concentration restored in 3-6 weeks
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22
Q

Vitamin B12 & folic acid

A
  • 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”
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23
Q

pernicious anemia

A
  • 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
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24
Q

folic acid present in

A

green vegetables, some fruits, and meats

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25
Q

folic acid deficiency

A
  • 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
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26
Q

circulatory effects of anemia

A
  • decreased viscosity
  • decreased O₂ (carrying capacity) → increases CO
  • markedly decreased exercise capacity
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27
Q

polycythemia

A
  • 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
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28
Q

polycythemia vera

A
  • clonal abnormality causing excessive proliferation
  • usually all lineages
  • 7 - 8 million RBCs, Hct 60-70%
  • hyperviscosity up to 3-fold from normal
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29
Q

polycythemia & circulation

A
  • 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
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30
Q

compensatory polycythemia

A
  • 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
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31
Q

first line of defense

A

mechanical barriers (skin & mucous membranes)

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32
Q

pathogen enters the body

A

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

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33
Q

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

A

non-specific immunity or inet

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34
Q

type of WBCs

A
  • polymorphonuclear neutrophils
  • eosinophils
  • basophils
  • monocytes
  • lymphocytes

circulate in the blood and may enter the tissues

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35
Q

WBC count

A

〜 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)

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36
Q

myeloid stem cell lineage

A
  • RBC
  • Granular leukocytes: eosinophil, basophil, neutrophil
  • monocyte
  • platelets
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37
Q

lymphoid stell cell lineage

A
  • B-cell
  • T-cell
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37
Q

neutrophils are __ cells that can respond __ to infection

A

mature; immedatley

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37
Q

monocytes mature in the __ to become __

A

tissues; macrophages

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38
Q

both exhibit motility:

A
  • diapedesis
  • ameboid motion
  • chemotaxis (chemoattractants: bacterla or tissue degradation products, complement fragments, other chemical mediators)
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39
Q

phagocytosis

A

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 *

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40
Q

specialized macrophages

A
  • 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
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41
Q

inflammation is driven by __ mediators and caharacterized by:

A

chemical

heat, redness, swelling and pain

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42
Q

physiologically, it involves:

A
  • vasodilation and increased blood flow
  • increased capillary permeability
  • coagulation of interstitial fluids
  • accumulation of granulocytes and monocytes
  • swelling of tissue cells
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43
Q

inflammatory mediators

A

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

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44
Q

different type of cytokines

A

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

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45
Q

neutrophilia

A

increase in neutrophil count

  • with intense inflammation, neutrophil can increase dramatically
  • results from mobilization of mature neutrophils form the bone marrow by inflammatory mediators
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46
Q

formation of pus:

A
  • 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
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47
Q

eosinophils

A
  • 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)
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48
Q

basophils

A
  • 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
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49
Q

leukopenia

A
  • 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
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49
Q

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

A

2; ulcer; infection

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50
Q

causes of leukopenia

A

radiation, chemical toxins, some medicines

in most cases marrow precursors can reconstitute normal blood cell counts with proper support

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51
Q

leukemia

A
  • uncontrolled production of abnormal WBCs d/t a genetic mutation
  • clonal, lineage-specific, often immature cells
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52
Q

leukemias are:

A
  • lymphocytic vs. myelogenous
  • acute vs. chronic (sometimes up to 10-20 yrs)
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53
Q

leukemias with partially differentiated cells may be classified as

A

neutrophilic, eosinophilic, basophilic, monocytic leukemias

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54
Q

clinical effects of leukemias

A
  • 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
55
Q

innate immunity

A
  • 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
56
Q

acquired / adaptive (specific) immunity

A

humoral → circulating antibodies
cellular → activated cells

57
Q

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

A

activated; organisms

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

57
Q

antigen

A
  • 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”
58
Q

2 types of lymphocytes

A

T-cells and B-cells

59
Q

lymphocytes mediate __ immunity

A

acquired

60
Q

where do lymphocytes develop?

A

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

61
Q

maturation of T cells in the thymus

A
  • 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

62
Q

B cell development and proliferation in response to antigen

A
  • 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
63
Q

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

A

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
64
Q

lymphocyte activation

A
  • 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
65
Q

B-cell activation and antibody production

A
  • 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
66
Q

Antibody/immunoglobulin: structure & sepcificity

A
  • 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
67
Q

antibody classes

A

IgM, IgG, IgA(breast milk), IgD(less than 1%), IgE

immunoglobulins make up about 20% of all plasma proteins

68
Q

What’s the earliest produced antibody?

A

IgM

69
Q

whats the most abundant antibody?

A

IgG (75% of all immunoglobulins)

cross the placenta

70
Q

which immunoglobulin is involved in allergic reactions?

A

IgE

71
Q

antibodies: mechanisms of action

A
  • 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)
72
Q

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

A
  • T cells only recognize antigen fragments that are presented by MHC molecules of antigen-presenting cells(APCs): macrophages, B lymphocytes, dendritic cells
73
Q

MHC molecules

A
  • 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
74
Q

Helper T cells (CD4)

A
  • 〜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
75
Q

General steps for helper T cell activation:

A
  • 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
76
Q

Immunologic tolerance

A
  • 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
77
Q

Cytotoxic T (CD8) cells

A
  • virus-infected cells
  • cancer cells
  • transplanted organs and tissues
77
Q

failure of immunologic tolerance results in

A

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
78
Q

active immunity is exposed by

A

antigen

infection with attenuated organisms

79
Q

passive immunity

A

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

80
Q

allergy and hypersensitivity

A
  • 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
81
Q

anaphylaxis

A
  • systemic, potentially fatal
  • widespread vasodilation
  • increased capillary permeability, volume loss
  • leukotrienes → bronchospasm and wheezing
  • treatment: epinephrine and antihistamines
82
Q

Uticaria

A
  • localized vasodilation and red flare
  • increased permeability and swelling “hives”
  • treatment: antihistamines
82
Q

hay fever

A
  • histamine-mediated
  • vascular dilation in the nasal passages and sinuses (and eyes)
  • leakage of fluid
  • sneezing
  • treatment: anti-histamines, local corticosteroids
83
Q

asthma

A
  • mediated by leukotrienes
  • sustained bronchospasm
  • treatment: B agonists, inhaled steroids, leukotriene receptor blockers, treat upper airway component
84
Q

transfusion RBC’s

A
  • packed red cells
  • increase O₂ carrying capacity
  • one unit increases hematocrit 〜3%
85
Q

transfusion platelets

A
  • single donation or apheresis
  • one unit raises platelet count 6-8,000/mL
  • indication < 50,000/mL, prior to surgery or with active bleeding
86
Q

transfusion FFP

A
  • single donation or apheresis
  • usually for coagulation deficiency
  • solvent/detergent plasma inactivates viruses
87
Q

transfusion cryoprecipitate

A

clotting factors

88
Q

Early transfusions

A
  • 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
89
Q

the ABO system

A
  • ** 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
90
Q

transfusion reactions: agglutination

A
  • RBC’s agglutinate
  • plug small vessels
  • physical distortion, phagocytic attack → hemolysis
  • in some cases, immediate, complement-dependent hemolysis
91
Q

The Rh(rhesus) antigens

A
  • 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
92
Q

Hemolytic disease of the newborn (erythroblastosis fetalis)

A
  • 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”)

93
Q

Hemolytic disease of the newborn: treatment

A
  • 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
94
Q

incompatibility: transfusion reactions

A
  • 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
95
Q

acute renal failure after transfusion reaction

A
  • 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
96
Q

autograft

A

graft obtained from same individual

97
Q

isograft

A

graft obtained from an identical twin

98
Q

graft acceptance/rejection

A
  • 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

98
Q

allograft

A

graft obtained from another individual/same speicies

99
Q

xenograft

A

graft obtained from an entirely different species

100
Q

rejection:

A
  • hyperacute rejection - Days
  • acute rejection - weeks
  • chronic rejection - months to years

rejection is mainly due to activated T cells (predominantly helper T cells)

101
Q

avoidance or suppression of rejection

A

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

102
Q

immunosuppressive drugs

A
  • 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

103
Q

immunosuppression: challenges

A
  • overwhelming infection, particularly viral infection
  • reduced tumor surveillance and increased incidence of cancer
104
Q

hemostasis: prevention of blood loss

A
  • vascular constriction
  • formation of a platelet plug
  • formation of a blood clot
  • healing of vascular damage +/- re-canalization
104
Q

vascular constriction

A
  • myogenic spasm
  • local autocoid factors from damaged tissued and platelets
  • nervous reflexes
  • smaller vessels: thromboxane A₂ released by platelets
105
Q

platelets

A
  • 〜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
106
Q

platelet functions

A
  • contractile compatibilities
  • actin, myosin, thrombasthenin
  • residual ER and Golgi: synthesize enzymes, prostaglandins, fibrin-stabilizing factor, PDGF, store Ca⁺
  • mitochondrial / enzymes: produce ATP, ADP
107
Q

platelet membranes:

A
  • surface glycoprotein: repels intact endothelium, adheres to injured endothelium and exposed collagen
  • membrane phospholipids: activate blood clotting
108
Q

formation of the platelet plug

A
  • 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
109
Q

clot formation and progression

A
  • 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
110
Q

fibrin production

A
  • 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
111
Q

clot extension

A
  • 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
111
Q

clot retraction

A
  • 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
112
Q

extrinsic pathway

A

trauma to the vessel wall and adjacent tissues

can be explosive, with clotting in < 15 seconds

113
Q

intrinsic pathway

A

trauma to the blood or exposure of the blood to endothelial collagen

much slower, 1-6 mins

114
Q

both pathways involve

A

clotting factors - mostly inactive proteases that are activated in cascades

115
Q

tissue injury →

A
  • tissue factor activates the extrinsic pathway
  • exposure of factor XII and platelets to collagen activates the intrinsic pathway
116
Q

prevention of clotting

A
  • 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
117
Q

heparin

A
  • 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
118
Q

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

A

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

119
Q

clot lysis

A
  • 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
120
Q

key events in hemostasis

A
  1. severed vessel
  2. platelets agglutinate
  3. fibrin appears
  4. fibrin clot forms
  5. clot retraction occurs
121
Q

causes of excessive bleeding

A
  • hepatocellular disease
  • vitamin k deficiency
  • hemophilia
  • low platelet count
122
Q

vitamin K

A
  • 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
123
Q

vitamin K deficiency

A
  • 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
124
Q

Hemophilia A

A
  • deficiency of factor VIII
  • 85% of hemophilia cases
  • 1/10,000 males
125
Q

Hemophilia B

A
  • deficiency of factor IX
  • 15% of cases
  • about 1/60,000 males
126
Q

both hemophilia’s

A
  • both impair intrinsic pathway activation
  • both genes on the X chromosome (males only get 1 copy)
  • clinically: bleeding after minor trauma
127
Q

Factor VIII deficiency

A
  • 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)
128
Q

throbocytopenia

A
  • 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
129
Q

Thrombus

A
  • 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
130
Q

pulmonary embolus

A
  • usually from deep leg veins
  • part of the thrombus disengages 〜10% of the time
  • occludes pulmonary arteries - potentially fatal
  • tPA can be life-saving
131
Q

clinical useful anticoagulants: heparin

A
  • binds, and potentiates antithrombin III
  • works rapidly, generally used acuteley
132
Q

clinical useful anticoagulants: Coumadins

A
  • inhibit VKOR c1
  • deplete active vitamin K → deplete active prothrombin, factors VII, IX, X
  • slower acting (days); used chronically
133
Q

clinical useful anticoagulants: In vitro anti-coagulation

A
  • 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
134
Q

prothrombin time

A
  • 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)”

Patho II (5 decks)

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