Pathology

Front 1

Symptoms of local inflammation

Back 1

– Swelling (tumour)
– Redness (rubor)
– Warmth (calor)
– Pain (dolor)
– Loss of function

Front 2

Describe the sequence of vascular changes in acute inflammation (vasodilation, increased permeability) and their purpose

Back 2

 Initial transient vasoconstriction
 Massive arteriolar vasodilation, result in increased blood flow: erythema and warmth
 Increased vascular permeability will result in swelling
 Increased engorgement of blood vessels will result in Slowing of blood flow (stasis)
 As stasis develops, leukocytes (mainly neutrophils) accumulate along the vascular endothelium: margination
 Residential phagocytic cells recognize the offending agent
 Secrete mediators to recruit other immune cells (cellular reaction)
 Mediators act on blood vessels (vascular reaction)

Front 3

Mechanisms that contribute to increased vascular permeability in acute inflammatory reactions

Back 3

A. Hyperemia
– Increased blood flow
– Due to vasodilation of the precapillary arterioles
– REDNESS and HEAT
– Mediated by histamine, bradykinin and prostaglandins
B. Increased Permeability
– The increased blood flow initially results in increased hydrostatic pressure, the fluid is a transudate
– Later, vessel permeability increases, the fluid is exudate
– Proteins are lost into the interstitial space (Exudation)
– SWELLING

Front 4

Know the mechanisms of increased vascular permeability. Know which vessels are affected in the immediate transient response

Back 4

1. Endothelial cell contraction leading to intercellular gaps in postcapillary venules (most common)
a. immediate transit response - mediated by histamine, bradykinin and prostaglandins ; rapid, short-lived
b. prolonged retraction – mediated by cytokines TNF and IL-1; slower, ≥ 24 hours
2. Endothelial injury
a. immediate sustained response – direct injury
b. delayed prolonged leakage – 2-12 hr delay
3. Leukocyte-mediated endothelial injury
4. Increased transcytosis of proteins
5. Leakage from new blood vessels

Front 5

Describe the steps involved in extravasation of leukocytes from the blood to the tissues. Know the steps at which selectins and integrins act. Figure 2-6 (PBD, p. 53) or Figures 2-5 and 2-7 (BP, p. 37, 39) will be helpful

Back 5

1. Margination-rolling-adhesion: Sialyl-Lewis X-modified glycoprotein bind to P & E-selectins; chemokines activate integrins which bind to ICAM-1
2. Transmigration: PECAM-1/CD31
3. Chemotaxis: Bacterial products (peptides); cytokines; complement; LTB4
4. Phagocytosis: recognition and attachment; engulfment; killing/degredation

Front 6

Define the terms edema, transudate, and exudate

Back 6

Two types of fluid leaving the intravascular compartment into the interstitial space:
1. Transudate:
– Low protein fluid
– Ultrafiltrate of plasma
2. Exudate:
– High protein fluid
– Increased permeability to protein molecules
– Leakage of proteins
1. Albumin
2. Globulins
3. Fibrinogen (if blood vessel is severely damaged) largest molecule
– It consists of erythrocytes that have leaked out of the very permeable and congested capillaries,
– Thin strands of fibrin derived from fibrinogen (protein) in the exuded plasma,
– Leukocytes that have exited the vessels via transmigration.

Front 7

Lymphangitis vs. Lymphadentis

Back 7

 During inflammation, the whole inflammatory exudate is removed by the lymphatics.
Lymphangitis - the lymphatics vessels become secondarily inflamed
Lymphadentis - the lymph nodes show reactive hypreplasia: increased in the number of lymphoid tissue

Front 8

Describe the meaning and utility of chemotaxis. The biochemical changes (PBD, p. 56-59; BP, p. 40-41) need not be memorized. Understand the role that chemokines play in inflammation

Back 8

Chemical gradient upon which leukocytes migrate, toward sites of infection or injury;
Chemotactics produced in response to infections and tissue damage and during immunologic reactions:
1. bacterial products (peptides)
2. cytokines
3. complement
4. LTB4
Chemokines bind to G-proteins

Front 9

Describe the steps involved in phagocytosis and the role of IgG and C3b as opsonins and receptors. Know the leukocyte receptors for these opsonins. Understand the role that collectins play in phagocytosis

Back 9

1. Recognition and attachment of the particle to the ingesting leukocyte
– Leukocyte binds to opsonins on microbe/protein:
(1) most importantly IgG antibodies on microbial surface antigens; bind to Fc receptor
(2) complement protein fragment C3; binds to CR1 & CR3
(3) collectins – plasma carbohydrate binding lectins; bind to microbial cell wall sugar groups; C1q
– IgG and C3 binding activates degradation of ingested microbes
2. Engulfment, w/ subsequent formation of a phagocytic vacuole
3. Killing and degradation of the ingested material

Front 10

Name Cell-derived mediators of inflammation

Back 10

Cell-derived:
1. Vasoactive amines: histamine, serotonin; cause vasodilation and invreased vascular permeability
2. AA metabolites: prostaglandins & leukotrienes
3. Cytokines: short range; mainly for leukocyte recruitment/migration; TNF, IL1, and chemokines

Front 11

Name the plasma derived mediators of inflammation

Back 11

Plasma-derived:
1. Complement proteins: creates breakdown products which cause leukocyte chemotaxis, opsonization/phagocytosis, cell killing
2. Coagulation proteins: activated factor XII triggers clotting, kinin and complement cascades
3. Kinins: mediate vascular rxn and pain

Front 12

Compare and contrast acute vs chronic inflammation with respect to causes, nature of the inflammatory response, and tissue changes

Back 12

Acute: minutes/days; neutrophils; increased permeability with
exudation of fluids and plasma proteins
Chronic: days/years; macrophages and lymphocytes (plus plasma cells, eosinophils, and mast cells); proliferation of blood vessels; fibrosis and tissue necrosis; active inflammation, tissue destruction, and repair/fibrosis are occurring simultaneously

Front 13

Compare and contrast the clinical settings in which different types of inflammatory cells (eg, neutrophils, eosinophils, monocyte-macrophages, and lymphocytes) accumulate in tissues. Compare and contrast the contents of neutrophil and eosinophil granules

Back 13

Differential WBC count will reveal
– Neutrophilia : Bacterial infection, granules contain contain three types of granules- small specific granules, larger nonspecific secondary granules (lysosomes), and also tertiary granules. The small specific granules contain enzymes and pharmacological agents that help Neutrophils phagocytose and destroy bacteria. The tertiary granules contain membrane and secreted proteins that help Neutrophils migrate to sites of infection.
– Eosinophilia: Parasitic infection or allergic
– Lymphocytosis: Viral infection
– Or sometimes leukopenia : Typhoid fever

Front 14

Distinguish between fibrinous, purulent, and serous inflammation. Define an abscess

Back 14

1. Fibrinous - Exudate has large molecule proteins, fibrinogen; appears as a “pink: eosinophilic mesh; Example inflammation which occurs in lining of body cavities; Pericarditis, pleuritis,meningitis
2. Purulent/Supperative - Large amount of exudate; Purulent exudate: pus, cellular debris and inflammatory cells; Bacteria (pyogenic bacteria)
Examples : abscess
3. Serous - Exudate is watery and protein poor; Example blister; If occurs into a serous body cavity it is called effusion; the epidermis separated from the dermis by a focal collection of serous effusion
4. Abscess

Front 15

Describe the systemic manifestations of inflammation and their general physiology, including fever, leukocyte left shift, and acute phase reactants

Back 15

Systemic inflammatory response syndrome (SIRS)
1. Fever - Mediated by IL-1 and TNF; Prostaglandins produced from arachidonic acid; NSAID block prostaglandin synthesis
2. Leukocytosis - predominantly neutrophils; 15,000 to 20,000 cells/ml; shift to left; immature leukocytes in the blood; In severe infection >40,000-100,000, referred to as Leukemoid reaction
3. Leukopenia
4. Acute phase response - Secretion of acute phase proteins (C reactive proteins, Fibrinogen, Serum amyloid A); in the lab investigations, high erythrocyte sedimentation rate (ESR) occurs because of the fibrinogen which binds RBC and cause them to sediment rapidly

Front 16

Describe the microscopic and gross morphological patterns in acute inflammation

Back 16

1. Microscopic
– Edematous
– Blood vessel dilation
– Inflammatory cell infiltration
2. Gross
– Serous
– Fibrinous
– Suppurative-Abscess
– Ulcer

Front 17

Compare and contrast the oxygen-dependent and -independent mechanisms of microbial killing and the relative importance of these two pathways. (Figure 2-11, PBD, p. 60 or Figure 2-10, BP, p. 42) is important to understand.) Know the disease that best exemplifies a leukocyte defect in oxygen-dependent microbicidal systems.

Back 17

1. Killing by oxygen species (ROS)= Oxidative burst
– Superoxide anion O2-
– Hydrogen peroxide H2O2
– Hypochlorous acid HOCL
– Myeloperoxidase coverts H2O2 to HOCL
2. Non-oxidative bacterial killing
– Lysosomal hydrolases (elastase) which degrade molecules
– Bactericidal permeability protein
– Lysozyme
– Major Basic Protein
– Defensin

Front 18

Describe the mechanisms of leukocyte defects in: (1) leukocyte adhesion deficiency, (2) myeloperoxidase deficiency, and (3) chronic granulomatous disease

Back 18

1. Leucocyte adhesion deficiency.
– Defective integrin expression
2. Chediak- Higashi syndrome.
– Defective lysosomal granules
3. Chronic granulomatous diseases
– No ROS is produced, hence no killing of microorganism
ALL PHAGOCYTIC DISEASES

Front 19

Define the term macrophage activation, and list the products of activated macrophages (Figure 2-28, PBD, p. 80 or Figure 2-21, BP, p. 55).

Back 19

– Macrophages are the dominant cells of chronic inflammation; can be found diffusely scattered in connective tissue or in liver as Kupffer cells, spleen and lymph nodes (histiocytes), CNS (microglial cells), and lungs (alveolar macrophages)
– Activated by nonimmunologic stimuli such as bacterial endotoxin or by cytokines from immune-activated T cells, particularly IFN-γ.
– Products in tissue injury/inflammation: ROS, proteases, cytokines (chemokines), coagulation factors, AA
– Products in fibrosis: Growth factors, fibrogenic cytokines, angiogenesis factors

Front 20

Define granuloma and list the causes of granulomatous inflammation

Back 20

– Granulomatous inflammation is a distinct pattern of chronic inflammation characterized by aggregates of activated macrophages that assume an epithelioid appearance
– Granulomas form in setting of persistent T-cell responses to certain microbes; or in response to relatively inert foreign bodies

Front 21

The differences between the various cell types (ie, labile, stable, and permanent cells) in terms of their regeneration potential. List examples of each cell type.

Back 21

1. Labile – continuously dividing cells; always being lost and replaced by maturation from stem cells and by proliferation of mature cells; hematopoietic cells in bone marrow, epithelia
2. Stable – quiescent cells; in the Go stage of the cell cycle; capable of proliferating in response to injury or loss of tissue mass; parenchyma of most solid tissues, endothelia, fibroblasts, SM cells; important for wound healing; limited capacity to regenerate after injury; liver (unlimited capacity), kidney (limited capacity)
3. Permanent – terminally differentiated and nonproliferative in postnatal life; neurons and cardiac muscle cells

Front 22

The main components of the cell cycle, for the moment appreciate that the cells involved in tissue repair will enter the cell cycle . Hence familiarize yourself with what kind of cells enter the cell cycle during repair and
Understand the role of cyclins and CDK in the cell cycle

Back 22

G1: Presynthetic growth phase;
S: DNA synthesis phase;
G2: Premitotic growth phase 2
M: Mitotic phase;

Nondivding cells are either in arrest in G1, or they exit the cycle to enter G0; progression from G1 is regulated by cyclins, which form complexes w/ enzymes called cyclin-dependant kinases (CDK’s)

Front 23

Understand what is meant by the following terms:
Proliferation, Stem cell (where do they come from), Differentiation

Back 23

1. Proliferation – ability of the cell to continue through the cell cycle
2. Stem cell – have self-renewal capacity and asymmetric replication (some enter differentiation pathway and some remain undifferentiated); if they have the capacity to generate multiple cell lineages (pluripotent) they can be isolated from embryos; normally present in proliferative tissues
3. Differentiation – ability to form a specific cell type

Front 24

You have already covered the ECM in histology, so simply review the following
The components of the ECM ; namely the basic forms of the ECM the matrix and the basement membrane
Understand the role of the ECM in tissue repair

Back 24

Components of ECM:
– Sequesters water, providing turgor to soft tissues & minerals, giving rigidity to bone
– Provides substratum for cell adhesion
– Reservoir for growth factors
= Regulates the proliferation, movement, and differentiation of the cells living within it.
– Its synthesis and degradation accompany morphogenesis, wound healing, chronic fibrotic processes, and tumor invasion and metastasis
1. Interstitial Matrix – a 3D amorphous gel; fibrillar/nonfibrillar collagens, fibronectin, elastin, proteoglycans, hyaluronate; synthesized by mesenchymal cells
2. Basement membrane – highly organized; synthesized by overlying epithelium and underlying mesenchymal cells; amorphous nonfibrillar type IV collagen and laminin; proteoglycans

Front 25

Roles of the ECM

Back 25

1. Mechanical support
2. Control of cell growth
3. Maintenance of cell differentiation
4. Scaffolding for tissue renewal
5. Establishment of tissue microenvironments
6. Storage and presentation of regulatory molecules

Front 26

You have already covered signal transduction, hence you know by now how the growth factor will stimulate the cells to proliferate.

Back 26

Growth factors drive the process of cell proliferation; promote entry of cells into the cell cycle

Front 27

Regeneration:
a. the type of cells
b. clinical conditions
c. associated features,
d. excessive tissue damage,
e. architectural framework
f. integrity of the tissue

Back 27

Regeneration:
Replacement of injured cells by the same type of cells
 It is the renewal of a damaged tissue by tissues identical to the original one.
 Tissues are derived from small number of unspecialized cells (Embryonic or Adult stem cells)
 Have the potential to replenish and regenerate
 Occur in labile and stable cells
 Occur from adult stem cells found in tissues or migrate from bone marrow
 Occur only if the structural framework of the tissue s intact

Front 28

Scar formation:
a. the type of cells
b. clinical conditions
c. associated features,
d. excessive tissue damage,
e. architectural framework
f. integrity of the tissue

Back 28

Scar formation:
Occurs in permanent cells or when tissue damage is severe; Replacement of injured cells by fibrous tissue (fibroblasts)
(1)angiogenesis (2)migration and proliferation of fibroblasts into the site of injury (3) deposition of ECM by these cells (4) remodeling; macrophages clear extracellular debris and fibrin at the site of injury and release mediators; largely inactive, spindle-shaped fibroblasts, dense collagen, fragments of elastic tissue, other ECM components;

Front 29

Identify the growth factor which is associated with cell and tissue regeneration; HGF,EGF,TGF-α

Back 29

HGF: Proliferation of epithelial and endothelial cells and of liver nonparenchymal; increases cell motility
EGF: Mitogenic for keratinocytes and fibroblasts; stimulates keratinocyte migration and granulation tissue formation
TGF-α: Similar to EGF; stimulates replication of hepatocytes and many epithelial cells

Front 30

How do growth factors initiate the process of proliferation and send their signals in tissue repair? Where do GF come from in tissue repair?

Back 30

 They bind to a receptor
 Trigger an event
 The signal is transduced into the cell
 Associate with the DNA
 Activate a transcription factor
1. Autocrine
2. Paracrine
- come from WBC’s, endothelium, and other inflammatory cells

Front 31

What is the role of the ECM surrounding the proliferating cells?

Back 31

 Provides support to proliferating cells
 Storage and presentation of Growth factors.
 Scaffolding for tissue renewal.
 Cells migrate through the ECM and adhere to ECM components.

Front 32

Angiogenesis

Back 32

– Either by sprouting of existing blood vessels (vascularization)
– Or by formation of new blood vessels by implanting Endothelial Precursors stem cells from Bone marrow

Front 33

Granulation tissue

Back 33

“organ of repair”; proliferating fibroblast; new blood vessels; loose connective tissue; contains capillaries, fibroblasts and inflammatory cells and macrophages

Front 34

Know the factors that are most important in determining whether regeneration will restore normal tissue architecture.

Back 34

Extensive regeneration or compensatory hyperplasia can occur only if the residual tissue is structurally and functionally intact, as after partial surgical resection. By contrast, if the tissue is damaged by infection or inflammation, regeneration is incomplete and is accompanied by scarring.

Front 35

Familiarize your self with the exceptional ability of the liver to regenerate itself and understand why fibrosis occurs in chronic liver diseases leading to cirrhosis of the liver.

Back 35

Liver has high regenerative ability after surgical removal; 40-60% of the liver may be removed in living-donor transplantation or partial hepatectomies; triggers proliferative response of the remaining hepatocytes (which are normally quiesant); initiated by cytokines (TNF & IL-6) that stimulate transition from Go to G1. When tissue injury is severe/chronic parenchymal cells and/or framework need to be repaired with connective tissue.

Front 36

Be able to identify the time frame for the following events
a. beginning of the repair process
b. time of appearance of granulation tissue

Back 36

Repair by connective tissue begins within 24 hours of injury by the emigration of fibroblasts and the induction of fibroblast and endo cell proliferation; by 3-5 days granulation tissue becomes apparent; Characterized by proliferation of fibroblasts and new thin-walled, delicate capillaries, ina loose ECM.

Front 37

Describe the components and the characteristic features of the granulation tissue; appreciate the role of the GT as organ of repair; Pay attention that granuloma IS NOT granulation tissue

Back 37

– Cells of granulation tissue: fibroblasts, myofibroblasts, macrophages Vascular
– Edematous - Leaky new endothelium
– Insensitive - Nerves in dermis destroyed
– Site where extracellular matrix (collagen) will be deposited

Front 38

Identify the growth factor responsible for each of the four phases of tissue repair.

Back 38

1. Formation of new blood vessels (angiogenisis) = VEGF
2. Migration and proliferation of fibroblasts = PDGF, FGF-2 & TGF-α; cytokines TNF & IL-1
3. Deposition of ECM = TGFβ and PDGF; cytokines
4. Maturation and reorganization of the fibrous tissue (remodeling) = FGF

Front 39

Describe how the scar eventually develops from the granulation tissue
Describe the components of scar tissue

Back 39

Fibroblast proliferation decreases; New blood vessel formation decreases; Synthesis of collagen increases;
Scar is composed of inactive spindle shaped fibroblasts, Dense collagen, ECM and a little bit of elastin; Avascular when mature. The collagen in the scar is fibrillar collagen; Synthesis begins 3-5 days; Attains maximum tensile strength with cross linking and in presence of vitamin C

Front 40

Define the term scar remodeling and appreciate the role of MMP collagenase in remodeling.

Back 40

– Removal of excess collagen is accomplished by collagenase enzymes; Matrix metalloproteiease MMP
– The outcome of the process of repair depends on the balance between Collagen and other ECM synthesis and Degradation
– Collagen degradation: Metalloproteinease enzymes are highly regulated, exist in inactive form, and require Zinc for their activation

Front 41

Describe the steps of cutaneous membrane skin repair

Back 41

1. Inflammation
• Clot formation
• Acute inflammatory response
2. Formation of granulation tissue
• Fibroblast migration and proliferation
• New blood vessel formation
3. ECM deposition and remodeling
• Collagen synthesis and deposition
• Collagen degradation

Front 42

Under which condition do tissues heal by fibrosis?

Back 42

When injury is severe or chronic, and results in damage to parenchymal cells and epithelia as well as the stromal framework, or if nondividing cells are injured, repair cannot be accomplished by regeneration alone. Repair must occur by replacement of the nonregenerated cells with connective tissue, or by a combination of regeneration of some cells and scar formation.

Front 43

Compare and contrast healing by first intention, noting the following
a. clinical conditions
b. associated features; infection, excessive contracture and granulation tissue

Back 43

a. Uninfected; Surgical incision
b. Incision causes only foacl disruption of epithelial basement membrane continuity and death of relateively few epithelial and connective tissue cells; epithelial regeneration predominates over fibrosis; borders are proximate to each other; adequate blood supply; minimal tissue destruction; small scar; minimal contracture

Front 44

Compare and contrast healing by second intention, noting the following
a. clinical conditions
b. associated features; infection, excessive contracture and granulation tissue

Back 44

a. extensive tissue destruction; ulcer; burns; abscesses
b. larger clot or scab; inflammation is more intense due to greater volume of necrotic debris, exudates, and fibrin; much larger amounts of granulation tissue are formed which leads to more excessive scaring and wound contraction

Front 45

Familiarize your self with the time framework of wound healing
a. When do you expect granulation tissue to appear
b. When do you expect epithelization to be evident in a surgical scar
c. When it is most likely that the scar will bleed excessively and why
d. When and how does the wound attains its maximum strength

Back 45

1. Thrombosis (scab)- w/in one day; neutrophils arrive; fibrin clot; barrier to microbes
2. Inflammation – 24 to 48 hours; dead cell/microbe removal; neutrophil liquification; macro’s clean
3. Reepithelization – 2 to 3 days; labile cells regenerate
4. Granulation Tissue – day 3; repair; replacement; neutro’s replaced by macro’s; capillary prolif; thin epithelium; vertically origin collagen fibers
5. BV Prolif – day 5; angiogenesis; horizontal collagen fibers; thick epithelium
6. Fibroblasts proliferation and matrix accumulation – week 2; collagen accum; inflammation decreases, less edema, bv & inflam cells; “blanching”
7. Scar formation – 1st month; avascular; epidermal cover complete; noninflammatory; no hair/nerves

Front 46

What are the factors that will delay healing?
Suboptimal wound repair?

Back 46

1. Location of wound; Blood supply; Coagulation defects; Infection (most important); Nutrition; Presence of foreign body; Diseases: DM and Atherosclerosis
2. Wound dehiscence ( mechanical stress spits open wound); trophic ulcers (in areas of inad blood supply; devoid of sensation; leprosy & diabetic peripheral neuropathy; keloid (excessive scar formation/ECM prod); irreg collagen and more abundant fibroblasts); excessive contracture (excessive myofibroblasts; palm, sole and anterior thorax); type of tissue (only stable/labile cells can heal); location/volume of the injury

Front 47

Appreciate the role of the following
Zinc
Vitamin C

Back 47

Vitamin C – coenzyme for lysyl-oxidase which catalyzes covalent bond formation/cross-linking in fibrillar collagen in the basement membrane of ECM
Zinc – required by metalloproteases; collagen degradation

Front 48

Will steroids delay or promote healing and why

Back 48

Glucocorticoids have well-documented anti-inflammatory effects, and their administration may result in poor wound strength due to diminished fibrosis; only desired in corneal infections to reduce likelihood of opaeity that may result from collagen deposition

Front 49

Define the following terms
Organization
Resolution
Proud flesh
And describe the conditions under which each occur

Back 49

1. Organization – if there is extensive exudate accumulation; granulation tissue (fibroblasts and bv’s) grows into the exudates; exudates transformed into fibrous tissue
2. Resolution - If there is no extensive cell death occurring the exudate is completely removed and the tissue returns to normal
3. Proud flesh -

Front 50

Describe wound strength

Back 50

 There is a rapid increase in the tensile strength at 7 to 14 days
 But it is only 10-20% of the ultimate strength
 Most of the strength results from cross linking of type I collagen and collagen synthesis exceeding collagen degradation
 70% of the strength is reached after 3 months

Front 51

Based on what you have learned so far about wound healing and tissue repair by fibrosis explain the pathogenesis of chronic inflammatory conditions such as Rheumatoid arthritis, pulmonary fibrosis and cirrhosis

Back 51

Persistant stimulation of collagen synthesis in chronic inflammatory diseases leads to fibrosis of the tissue.

Front 52

) Name the two main groups. For each group, know two subgroups.

Back 52

Cell-derived
- Vasoactive Amines
- Arachidonic Acid Metabolites
b. Plasma protein-derived
- Complement
- Coagulation and Kinin Systems

Front 53

Name two vasoactive amines that are cell-derived mediators of inflammation.

Back 53

a. Histamine
b. Serotonin

Front 54

Name the major precursor of eicosanoids that are C20 polyunsaturated fatty acid.

Back 54

Arachidonic Acid

Front 55

) Name three groups of eicosanoids
Which of three groups are in the cyclo-oxygenase (COX) pathway? Which group is in the lipoxygenase pathway?

Back 55

- Prostaglandin, Thromboxane and Leukotriene
b. Prostoglandins and Thromboxanes c. Leukotrienes

Front 56

Become familiar with the site of action of NSAIDS (nonsteroidal anti-inflammatory drugs) and steroids (corticosteroids/ glucocorticoids).

Back 56

The NSAIDS inhibit cyclooxygenase, which stops production of prostaglandin. Whereas steroids suppress phospholipase A2. By inhibiting phospholipase A2, the production of Arachidonic acid ceases.

Front 57

) How does bradikinin (kinin system) interact with the biosynthesis of arachidonic acid?

Back 57

Activates phospholipase A2

Front 58

Know differences between COX I and COX II.

Back 58

COX I – the housekeeper, responsible for maintaining GI mucosal integrity, platelet aggregation and renal function
COX II – inflammatory, responsible for mitogenesis and growth, female reproduction regulation, bone formation, renal function, and reduces platelet aggregation.

Front 59

Become familiar with the role of leukotrienes in asthma.

Back 59

Murakami talked about aspirin induced asthma. This happens because aspirin inhibits the cyclooxygenase pathway which then leads to an increased utilization of the lipoxygenase pathway. This then produces more leukotrienes which can be potent bronchoconstrictors = asthma.

Front 60

Outline the main effects of prostaglandins on vascular cells, thrombosis and inflammation.

Back 60

Smooth muscle contraction: PGF(2-alpha)
Smooth muscle relaxation: PGD(2), PGE (2), PGE(1)
Platelet aggregation: TXA(2)
Inhibition of platelet aggregation: PGI(2)