Mod 2 Inflammatory Response

Question 1

Innate Defences

Answer 1

-Non-specific
-No immunological memory
-Fluids (flushing, tears, saliva, mucous, sweat, gastric acid, urine)
-Barriers (skin, mucous membranes, microbiome)
-Phagocytosis/Apoptosis
-Chemical mediators (histamine, pro inflammatory plasma proteins, cytokines, chemokines)
-Inflammation (redness, heat, swelling, pain, loss of function)
-Fever

Question 2

Adaptive Defences

Answer 2

-Specific
-Long-term immunological memory
-Immune responses
-B cells: plasma cells: antibody mediated humoral responses
T cells: cell mediated: direct cytotoxic attack
-Both immunological memory response

Question 3

Possible outcomes

Answer 3

-Body Defenses successful = Health or Healing
-All Defences overcome = injury or disease

Question 4

Innate Immunity

Answer 4

-Also called natural immunity because you are born with these immune functions although may not be fully functional at birth
-Innate responses to a foreign antigen should be immediate, but they do not provide immunological memory (can become ill from same pathogen again)

Question 5

Adaptive immunity

Answer 5

-Contains both PASSIVE (you receive antibodies from someone else) and ACTIVE (you make the antibodies/T helper cells) branches
- Not fully functional at birth, functional at 2
-Takes time to develop 7-14 days for first exposure, then faster for subsequent exposures because of immunological memory (ie presence of b/t memory cells)

Question 6

Antibodies

Answer 6

-Called immunoglobulin (ig)
-Five classes igA,igD,igE,igG,igM
-Presence of specific antibodies in plasma indicated exposure to specific antigen

Question 7

What is an antigen?

Answer 7

Usually foreign, causes body to respond

Question 8

What happens if 1st line of defence is intact

Answer 8

Nothing, stay healthy, foreign agent can’t enter

Question 9

What happens if 1st line of defence breached?

Answer 9

May get infection, tissue breakdown

Question 10

What happens if 2nd line of deference is activated

Answer 10

Inflammation, plasma protein systems activated (clotting), chemical mediators

Question 11

Purpose of acute inflammatory response

Answer 11

Destroy or wall off, promoting healing
Main chemical mediator is histamine

Question 12

What activates adaptive immune system (3rd line of defence)

Answer 12

Histamine release, when second line of defence fails, when b/t cells respond

Question 13

At what age is adaptive fully functional and when does it start to wane

Answer 13

2, 40

Question 14

B cell stimulates ___, T cell stimulates ___

Answer 14

Plasma cells and antibodies
Cell mediated immunity release of cytotoxins

Question 15

What happens if innate/adaptive immune defences are not successful

Answer 15

Stay sick, death, chronic infection/inflammation

Question 16

What happens if too much histamine is released

Answer 16

Hypersensitivity, allergies

Question 17

What happens if not enough histamine is released

Answer 17

Immunodeficiencies, more likely to get infection, slower wound healing

Question 18

What is inflammation?

Answer 18

-Body’s response to tissue damage/infection
-Occurs at the tissue level
-Inflammatory response is initiated by stromal cells, especially mast cells and fibroblasts in connective tissue
-Also requires microvascular response and a variety of pro inflammatory chemical mediators
-Can be acute or chronic
-Often multifactorial, involving both environmental and genetic factors

Question 19

Tissues are made up of:

Answer 19

Stromal cells, parenchyma cells, and interstitial tissue fluid

Question 20

How well an injured tissue heals depends on

Answer 20

Level of vascularization, and type of parenchyma cells in that tissue (can they regenerate)

Question 21

5 Signs of Inflammation

Answer 21

Redness
Heat
Swelling (edema)
Pain
Loss of function

Question 22

Swelling (Edema)

Answer 22

Increase in amount of interstitial tissue fluid
Ie. fluid between the cells; pressure of the excess tissue fluid may irritate nerve endings eliciting pain

Question 23

Loss of function

Answer 23

Usually due to the pain, especially within a joint, also due to swelling causing decreased range of motion

Question 24

What is the inflammatory response?

Answer 24

-Part of second line of innate immune defence
-Occurs when first line of defence breached
-Non-specific, rapid response of injured tissue to any etiological agent of tissue damage
-3 Components: vascular, cellular, and biochemical (plasma protein) responses to tissue damage

Question 25

What are the 3 major causes of tissue damage

Answer 25

Genetic, congenital, or acquired

Question 26

Purpose of Inflammatory response

Answer 26

1. Limit further tissue damage Destroy or dilute out causative agent 2. Prevent spread of injurious agent/infection To wall off causative agent 3. Stimulate adaptive immune responses If innate inflammatory response not able to destroy causative agent 4. Begin wound healing process To bring nutrients, remove wastes (including cell debris) — not all responses need all 4 of these utilized Eg if minimal damage like a paper cut, only need diluting out causative agent and nutrient/waste exchange necessary

Question 27

Role of stromal and parenchyma tissues

Answer 27

Both tissues respond to tissue damage

Question 28

Stromal tissues

Answer 28

Microvasculature: arterioles, capillaries, venules . Endothelial cells increase vascular permeability . Vascular smooth muscle cells vasodilate Connective tissues: . Supportive, binding tissues Eg areolar CT . Fibroblasts secrete protein fibres collagen . Mast cells secrete histamine and heparin - stromal response to injury triggers the inflammatory response with pro inflammatory chemical mediator histamine

Question 29

Parenchyma tissue

Answer 29

The functional cells of the tissue May be injured and need to heal or be replaced Do not directly cause the inflammatory response, simply trying to survive and if possible replace cells that have died

Question 30

Microvasculature

Answer 30

-Consists of microscopic blood vessels: arterioles, capillaries, and venules -All lined with endothelial cells -Arterioles and venules contain smooth muscles in their walls -Capillaries are simple tubules of endothelium -All surrounded by connective tissue -all have different roles in inflammatory response

Question 31

Connective tissues

Answer 31

-Supportive, binding tissues -Areolar CT most common type of CT found in every body organ, directly below covering or lining cells called epithelial cells -Two main types of stromal cells in CT involved with inflammatory response are fibroblasts and mast cells

Question 32

Fibroblasts

Answer 32

-secrete proteinaceous fibers that help form the structural framework of all connective tissues (collagen, elastin and reticulin)

Question 33

Collagen

Answer 33

-Important CT fibre involved in inflammatory response and wound healing -Helps to stabilize and form the structural framework of the wound site during wound healing -Also helps trigger blood clotting (coagulation) by interacting with platelets -Clotting necessary if blood vessels are damaged and the individual is bleeding

Question 34

Mast cells

Answer 34

-Tissue WBC that secrete histamine during the inflammatory response -Along with basophils also secrete heparin to help prevent unwanted blood clotting within uninjured tissues and the blood stream

Question 35

Histamine

Answer 35

-Potent arteriole vasodilator -Increases blood flow into the injured tissue -Basophils in the blood stream can also secrete histamine, important if tissue damage occurs to the inside of a blood vessel

Question 36

If parenchyma cells cannot be replaced

Answer 36

If cannot be replaced by mitosis, tissue/organ deficits may occur

Question 37

2 types of parenchyma cells that cannot undergo mitosis

Answer 37

Heart cardiac cells Neurons

Question 38

2 patterns of inflammatory response based on:

Answer 38

The duration of response The specific WBCs present in the lesion 1. Acute inflammatory response 2. Chronic inflammatory response

Question 39

Acute Inflammation

Answer 39

-Innate, immediate tissue response to injury -Main chemical mediator: Histamine -Tries to limit the damage and prevent scarring -Promotes wound healing by bringing in nutrients and removing debris -Predominant immune cells: Mast cells, neutrophils, macrophages

Question 40

Chronic Inflammation

Answer 40

-Innate and adaptive, prolonged tissue reaction to continued injury or persistent infection -Main chemical mediator: histamine -Still trying to limit the damage and promote would healing, but scarring probable -Predominate immune cells: macrophages, lymphocytes, and mast cells

Question 41

Neutrophils

Answer 41

-Known as first responders -Can detect low levels of distress signals (Chemicals released by damaged cells and microbes) -Arrive within hours of injury -Try to phagocytize debris and pathogens, but are often destroyed by the pathogen

Question 42

Macrophages (M1)

Answer 42

-A few reside within all normal, healthy connective tissue -However once inflammatory response is triggered, chemicals released by microbes, damaged body cells, and dead and dying neutrophils stimulate a massive influx of new monocytes into injury site -Monocytes quickly undergo morphological change to become macrophages (M2)

Question 43

Macrophages (M2)

Answer 43

-Commonly known as the “clean up” cells -Show up a bit later in acute inflammatory response and promote wound healing -Stick around and work with the lymphocytes if the wound site becomes a chronic issue

Question 44

Acutely inflamed tissue has

Answer 44

Lots of neutrophils, a few M1 —> M2 (dependent on extent of injury)

Question 45

Chronically inflamed tissue

Answer 45

Some M1 —> lots of M2 + lots of lymphocytes (combination of dendritic cells, NK cells, and T lymphocytes -Within chronically inflamed site, will see aspects of acute and chronic inflammatory responses to the persistent causative agent of injury -Pathologist would be able to determine specifics by recognizing the WBC’s in tissue sample -Mast cell numbers will fluctuate based on acuity of reinjury

Question 46

“Repair” implies

Answer 46

-Scar tissue has been produced -in wound healing, regeneration and resolution are the preferred outcomes -Hallmark of chronically inflamed tissues is scarring

Question 47

Characteristics of acute inflammatory response

Answer 47

-Begins within seconds -Innate, non-specific, no immunological memory -Includes 3 proinflammatory responses to tissue damage

Question 48

Acute inflammatory benefits

Answer 48

Used to prevent spread of infection, bring in nutrients and remove wastes, limit further tissue damage and promote wound healing

Question 49

Acute 3 pro-inflammatory responses to tissue damage

Answer 49

1. Vascular (microvascular) responses -mediated by histamine —> promote vasodilation and increase vascular permeability 2. Cellular responses -mediated by WBCs -may include platelets, rbcs, and fibroblasts -major WBCs involved: mast cells (secrete histamine) neutrophils, macrophages (clean up cellular debris) 3. Plasma protein systems responses 3 types: complement, coagulation, and kinin cascades —> promote inflammation, blood clotting

Question 50

Pro inflammatory plasma proteins acute phase proteins

Answer 50

-Most are made in the liver and/or injured tissues -They circulate at at a low level in the blood plasma as inactive enzymes -When inactive proinflammatory mediators enter the injury site, they become active enzymes that catalyze different aspects of the inflammatory response -Operate in a cascade or domino effect -In response to calls for help from the injured tissues, the liver increase production

Question 51

3 Major components of acute inflammatory response

Answer 51

1. The vascular response 2. The cellular response 3. The plasma protein systems response

Question 52

The inflammatory response begins with…

Answer 52

-The release of histamine from granules stored within tissue mast cells -Release of histamine is known as MAST CELL DEGRANULATION -Once released, histamine can trigger all 3 components of acute inflammatory response

Question 53

The Vascular Response

Answer 53

-Immediate histamine-mediated response by the microvascular endothelial and smooth muscle cells within wound site -Will increase blood flow into the injured tissue and increase vascular permeability

Question 54

The Cellular Response

Answer 54

-Includes all 3 types of blood cells (wbc, rbc, platelets) as they respond to injured tissues distress signals

Question 55

The Plasma Protein Systems Response

Answer 55

-Includes a variety of biochemical responses to injury -Proinflammatory proteins are part of acute phase proteins -Transported in blood plasma to injury site to act as proinflammatory mediators

Question 56

3 Cascades of Plasma Proteins

Answer 56

-Interrelated functions -Complement system -Coagulation (clotting) system -Kinin system (weak histamine like effects, elicits pain)

Question 57

Entire response depends on the chemical mediator ___ released by local tissue ____ cells

Answer 57

Histamine, mast cells

Question 58

Mast cells are located in ..

Answer 58

CT surrounding the microvasculature

Question 59

Histamine receptors are located on..

Answer 59

Endothelial cells Smooth muscle cells

Question 60

Unlike larger arteries and veins, microvasculature of an organ can..

Answer 60

Be increased or decreased depending on organs need, becomes more extensive the more fit you are

Question 61

Tissue damage stimulates mast cells to..

Answer 61

-Rapidly degranulate which releases histamine from storage in cytoplasmic vesicles -Histamine binds to histamine receptor on vascular endothelial and smooth muscle cells causing specific INDEPENDENT responses

Question 62

Effects of Histamine on Microvasculature

Answer 62

1. Arteriolar and precapillary sphincter smooth muscle cells —> histamine stimulates vascular smooth muscle cells to relax —> arteriole vasodilation + opens (relaxes) precapillary sphincters —> increased rate of blood flow into capillary bed 2. Venular endothelium (minor effect on capillaries) —> histamine stimulates endothelial cells to contract —> myoendothelial contraction creates inter-endothelial cell gaps —> increased vascular permeability 3. Venular endothelium —> histamine also stimulates endothelial cells to decrease production of anti-endothelial adhesion proteins —> allows WBC’s, platelets, and/or rbc’s to squeeze between endothelial cells and infiltrate wound site —> promotes leukocyte infiltration and clot formation

Question 63

2 Smooth muscle vascular damage effects

Answer 63

1. Arteriolar vasospasm -Immediate but brief vasospasm as smooth muscle contracts in response to sympathetic NS release of epinephrine (transient vasoconstriction stress response to injury) -Followed quickly within seconds by arteriolar vasodilation (smooth muscle relaxes)

Question 64

Mast cells

Answer 64

-Innate tissue immune cells that recognize and respond to tissue “distress” signals by secreting histamine and other proinflammatory mediators including heparin

Question 65

Mast cell characteristics

Answer 65

-Derived from pluripotent stem cells in red bone marrow -Reside in connective tissues -Stromal immune surveillance cells -Related to basophils, same jobs but reside in different places -Recognize tissue damage, microbial invasion

Question 66

How mast cells recognize tissue damage

Answer 66

Have lots of cell surface receptors that can bind to a variety of foreign antigen or injured body cell chemical distress signals Ag receptor binding —> triggers mast cell activation —> histamine secretion

Question 67

Histamine is a

Answer 67

Proinflammatory protein

Question 68

Heparin

Answer 68

-Secreted by mast cells and basophils -Anticoagulant -Basophils secrete into bloodstream, Mast cells secrete into stromal connective tissue -When secreted into bloodstream, prevents platelets from spontaneously aggregating together forming a intravascular thrombus -When secreted in stromal tissues, helps with dissolution (break down) of a clot as a wound heals

Question 69

Mast cells vs basophils

Answer 69

-Both derived from same red bone marrow stem cells called pluripotent stem cells -Have similar functions -Located in two different places -Mast cells leave the blood stream to reside in tissues (Eg CT, dermis) -Basophils remain in bloodstream (<1% of peripheral blood wbcs)

Question 70

Immune cell receptors

Answer 70

PRRs PAMPs DAMPs TLRs Binding of these chemicals to any of these receptors triggers mast cell to respond

Question 71

Pattern recognition receptors (PRRs)

Answer 71

Recognize/bind microbial cell surface chemical patterns

Question 72

Pattern associated molecular patterns (PAMPs)

Answer 72

Recognize/bind products of microbes

Question 73

Damage associated molecular patterns (DAMPs)

Answer 73

Recognize/bind products of body cellular damage (your body’s own distress signals)

Question 74

Till like receptors (TLRs)

Answer 74

Recognize/bind to a variety of microbial cell wall or surface chemicals

Question 75

Mast cells release proinflammatory mediators by 2 mechanism

Answer 75

1. Mast cell degranulation 2. Mast cell synthesis

Question 76

Mast cell degranulation

Answer 76

-immediate release of proinflammatory mediators -mediators made in advance and stored in vesicles within mast cells (look granular) -releases histamine (elicits all 5 signs of inflammation) that stimulates vascular, cellular and plasma protein responses -releases chemotactic factors (named for wbc they attract -releases cytokines (interleukins, tumor necrosis factors) -

Question 77

Mast cell synthesis

Answer 77

-Slower release of newly synthesized mediators by activated, often injured mast cells within site of tissue damage “distress signals” -Includes cell membrane components of damaged mast cells —> solubilized (dissolve) in tissue fluids —> signal other wbcs to area of damage -chemokines - leukotrienes, prostaglandins, & platelet activating factor

Question 78

What is most potent proinflammatory mediator

Answer 78

Histamine

Question 79

Liver makes

Answer 79

Most of the plasma protein system mediators

Question 80

Chemotactic factor

Answer 80

Help stimulate specific types of WBC’s to the area of tissue damage Includes: neutrophil chemotactic factor, eosinophil chemotactic factor

Question 81

Cytokines

Answer 81

Are communication signals between wbcs, allow them to alert each other to problems “cross talk” Include: interleukins (ILs) and Necrosis factor (TNF)

Question 82

Chemokines

Answer 82

Chemicals involved in inflammatory response that help wbcs migrate to site of tissue damage Type of distress signal released by mast cells and other damaged cells in injury site Include actual components of the damaged cells Eg normal cell membrane components that are released into tissue fluid as a cell dies “hence distress signals” Include: leukotrienes, prostaglandins, and platelet activating factor

Question 83

Histamine does not directly cause

Answer 83

Pain However because it stimulates edema that pushes on nerve endings causing them to be compressed or irritated, it is said to elicit all 5 even though one is indirect

Question 84

I’m response to tissue damage mast cells produce and release a lot of different proinflammatory mediators by 2 processes:

Answer 84

Degranulation Synthesis

Question 85

Proinflammatory mediators that are made by mast cells in advance and stored in secretory granules are quickly released by

Answer 85

Degranulation

Question 86

Proinflammatory mediators released by degranulation

Answer 86

Histamine, chemotactic factor, cytokines

Question 87

Proinflammatory mediators that are made by mast cells in direct response to injury are called:

Answer 87

Newly synthesized

Question 88

Newly synthesized made from

Answer 88

Mast cell cell membrane protein (enzyme) called phospholipase A2 as the mast cell becomes activated

Question 89

Synthesized Proinflammatory mediators

Answer 89

Prostagladins Leukotrienes Platelet activating factor

Question 90

Biochemistry of mast cell synthesis pathways derived from:

Answer 90

Phospholipase A2 When released from mast cells cell membrane, becomes soluable (dissolves in tissue fluid) Proinflammatory enzyme that quickly stimulates production of several other Proinflammatory chemicals

Question 91

Degranulation pathway

Answer 91

Mast cell —> Histamine (vascular effects)/Cytokines (inflammation)/Chemotactic factors —> Neutrophil chemotactic factors (attracts neutrophils)/Eosinophil chemotactic factor (attracts eosinophils)

Question 92

Mast cell synthesis pathway

Answer 92

Mast cell —> phospholipase A2 —> platelet activating factor (vascular effects, platelet activation)/Arachidonic acid —> Cyclooxygenase/5-Lipoxygenase —> prostaglandins (vascular effect, pain)/leukotrienes (vascular effects)

Question 93

Histamine is a

Answer 93

Proinflammatory vasoactive amine Affects microvasculature and other target tissues

Question 94

Histamine binds to

Answer 94

Histamine receptors located on cell membrane of specific target cells Effects vary depending on specific target cell and subtype of histamine receptors

Question 95

2 types of histamine receptors

Answer 95

H1, H2

Question 96

H1 receptors

Answer 96

Proinflammatory effects on target cells: Endothelial cells Vascular smooth muscle Bronchiole smooth muscle Immune cells (WBCs) Most common type

Question 97

H2 receptors

Answer 97

Antiinflammatory effects on target cells: Gastric parietal (HCI secreting) cells Immune cells (WBCs)

Question 98

Although histamine is considered a major Proinflammatory mediator is has some ..

Answer 98

Anti inflammatory effects depending on which type of histamine receptors it binds, h1 or h2

Question 99

H1 endothelial

Answer 99

Histamine H1 receptor binding on vascular endothelial cells —> changes gene expression —> actin (contractile/motility protein) produced —> stimulates endothelial cell contraction —> creates small gaps between endothelial cells —> increase vascular permeability; lots on venular endothelial cells

Question 100

H1 vascular smooth muscle cells

Answer 100

H1 rectory or binding on vascular smooth muscle cells —> stimulates smooth muscle relaxation —> arteriole vasodilation; lots on arteriole smooth muscle cells

Question 101

H1 bronchiole smooth muscle cells

Answer 101

H1 receptor binding on bronchiole smooth muscle cells —> stimulates bronchiole smooth muscle contraction —> bronchiole constriction —> decreased gas exchange Occurs in asthma, anaphylaxis

Question 102

H1 neutrophils and mast cells

Answer 102

H1 receptor binding on neutrophils and mast cells —> promotes neutrophil infiltration and mast cell prostaglandin synthesis Both are Proinflammatory

Question 103

H2 gastric parietal cells

Answer 103

H2 receptors binding on gastric parietal cells —> stimulates increased gastric acid secretion —> needed for protein denaturation (digestion) but has added benefit of denature glucose microbial proteins in the food we eat; hence anti inflammatory

Question 104

H2 WBC’s

Answer 104

H2 receptor binding on WBCs —> decreases inflammatory response; part of the anti inflammatory events that occur as wound healing begins Note: many immune cells have both H1/H2 receptors (they can switch type)

Question 105

H1/H2 receptor switching

Answer 105

Depending on where the tissue is within the continuum from acute injury to wound healing, target cells can switch the number of h1 or h2 receptors on their outer cell membrane Eg. Some WBCs switch from Proinflammatory H1 receptions during inflammatory response to H2 receptors as the inflammatory response wands and wound healing progresses Other cell types only have one type of histamine receptor Eg, gastric parietal cells

Question 106

Antihistamines are

Answer 106

H1 receptor antagonists

Question 107

H2 secretion on gastric acid

Answer 107

Lymphocyte = decreased activity Eosinophils = decreased activity Neutrophils = decreased chemotaxis Mast cell = decreased degranulation

Question 108

Effects of histamine on smooth muscle depends on

Answer 108

Target organ In microvasculature—> vascular smooth muscle relaxation —> vasodilation = redness + heat In bronchioles —> smooth muscle contraction —> bronchiole construction

Question 109

Anti inflammatory drugs

Answer 109

Antihistamines, glucocorticoids, NSAIDS All have different pharmacokinetics

Question 110

If mast cell is destroyed

Answer 110

Then lots of phospholipase A2 would be released. Quickly metabolized into arachidonic acid and platelet activating factor

Question 111

Prostaglandins and leukotrienes

Answer 111

Both Proinflammatory distress signals noted by many immune cells

Question 112

NSAIDS

Answer 112

-non-steroidal anti-inflammatory drugs -include aspirin (ASA, acetylsalicylic acid) and ibuprofen

Question 113

NSAIDS ASA pathway

Answer 113

-ASA blocks the arachidonic acid —> cyclooxygenase (COX) pathway thus has 1) anti inflammatory effects —> decreases vascular effects including pain and swelling and 2) decreases pain signals —> analgesic effects -ASA also blocks thromboxane A2 which is a pro-coagulant chemical released by activated platelets that promotes platelet plug formation = ASA is also an anticoagulant -Other NSAIDS block the cyclooxygenase pathway = production of prostaglandins is decreased which decreased vasodilation and vascular permeability —> anti inflammatory effects that decrease Acetaminophen only block the pain component of the cyclooxygenase pathway —> PG synthesis pathway thus does not have anti inflammatory effects

Question 114

Corticosteroids/glucocorticoids

Answer 114

-Steroidal drugs (aka prednisone, cortisone, hydroxycortisone) and the hormone cortisol made by adrenal cortex that block the release of phospholipase A2 -By blocking PLA2 release, cortisol prevents the production of both the COX and LOX pathways thus blocking prostaglandins and leukotrienes making it a potent anti inflammatory -Glucocorticoids also block histamine release

Question 115

Antihistamines

Answer 115

Histamine antagonists that block histamine binding to H1 receptors = they also decrease vascular and bronchiole inflammatory responses

Question 116

Cortisol

Answer 116

Major mediator of the stress response that affects both innate and adaptive immune function

Question 117

Summary Proinflammatory blockage

Answer 117

Antihistamines/glucocorticoids = block histamine and vascular effects Glucocorticoids = block phospholipase A2 production ASA =block cyclooxygenase NSAIDS = block cyclooxygenase pathway/prostaglandins

Question 118

Endothelial responses to histamine stimulation

Answer 118

Location: venules and capillaries (minor role) Histamine receptor: H1 Physiological effects: 1) increased actin gene expression —> increased actin production (contractile/motility protein) —> myoendothelial cell contraction —> inter endothelial cell gaps —> increased local vascular permeability —> edema, pain, loss of function + WBC infiltration and: 2) decreased endothelial cell anti adhesion gene expression —> blood cells adhere to endothelium —> WBC infiltration + platelet adhesion —> platelet activation —> coagulation (clotting)

Question 119

Vascular smooth muscle response to histamine stimulation

Answer 119

Location: arterioles & precapillary sphincters Histamine receptor: H1 Physiological effect: Histamine H1 receptor binding —> vascular smooth muscle relaxation —> arteriole vasodilation and precapillary sphincters open —> increased local blood flow into capillary bed —> redness and heat

Question 120

Histamine-mediated physiological effects via H1 receptor

Answer 120

Binding causes Proinflammatory effects of the microvasculature, usually local to the wound site

Question 121

Systemic vascular Proinflammatory repose

Answer 121

Can occur and may be life threatening due to changes in BP, HR, and blood volume (massive systemic arteriole vasodilation), peripheral (including laryngeal) edema, and bronchiole constriction =serious effects of an anaphylactic reaction to an allergen

Question 122

ARTERIOLE microvascular response to histamine H1 receptor binding

Answer 122

Smooth muscle relaxes —> arterioles vasodilate —> increased lumen size —> increased local blood flow —> redness and heat Occurs mainly on arteriole smooth muscle cells because these smooth muscle cells have the most H1 receptors

Question 123

PRECAPILLARY SPHINCTERS response to histamine H1 receptor binding

Answer 123

Smooth muscle relaxes to open sphincter —> increased lumen size —> increased blood flow into capillary bed —> redness and heat

Question 124

VENULES response to histamine H1 receptor binding

Answer 124

Actin gene expressed —> myoendothelial cell contraction —> interendothelial gaps allow fluid to leave plasma and enter tissues —> increased vascular permeability —> increased local tissue fluid volume —> edema + WBC infiltration into wound site + increased platelet adhesion to endothelium leading to potential coagulation (clotting) cascade, if the blood vessels are damaged Occurs mainly in venule endothelium because these endothelial cells have the most H1 receptors

Question 125

CAPILLARIES response to histamine H1 receptor binding

Answer 125

Only endothelial cells, no smooth muscle Can passively expand a bit as increased blood flow from arteriole increases pressure in the capillaries; some myoendothelial cell contraction —> increased vascular permeability

Question 126

Endothelial cell contraction mechanism via actin

Answer 126

-Histamine binding to H1 receptors stimulates endothelial cells to change their normal gene expression and produce a bit of the protein actin -Once produced actin stimulates the cells to retract their cell membranes allowing microscopic gaps to form between the cells -Plasma components and WBC’s can leak out of these interendothelial gaps into surrounding tissue fluid, actin will play a role in wound healing -Histamine also allows all blood cells to come in contact with the endothelium, Will allow phagocytic WBCs to infiltrate the wound site and also promote platelet activation to stimulate coagulation if the tissue damage included injury to the blood vessels, blood clot needed to stop the bleeding -Healthy endothelial cells express anti adhesion proteins on their outer surface to help prevent blood cells from sticking to them and blocking blood flow. During inflammatory response WBCs need to be able to infiltrate the wound site and platelets which help RBCs need to be able to plug holes in the blood vessel wall. All blood cell types need to be able to adhere to the endothelium, thus the local endothelial cells stop expressing anti adhesion proteins allowing the blood cells to adhere

Question 127

Blood flow in normal uninjured blood vessel

Answer 127

-Axial streaming of blood cells -Plasma in the plasmatic zone -Minimal gaps between endothelial cells -Endothelial cells secrete anti-adhesion chemicals

Question 128

Blood flow in acutely inflamed blood vessels

Answer 128

-Histamine mediated myoendothelial cell contraction —> interendothelial cell gaps lead to -Increased vascular permeability -Endothelial cell secretion of pro-adhesion chemicals (CAMS) -Blood cells enter plasmatic zone —> adhere to endothelium —> enter wound site

Question 129

Normal blood flow physiology

Answer 129

-Normal blood flow is smooth, laminar flow that allows blood cells to travel in the central (axial) zone of the blood stream called axial streaming and lubricating plasma to flow against the endothelial walls of the vessel in the plasmatic zone -Axial streaming keeps blood cells away from the endothelial cells

Question 130

Normal blood flow: Plasma

Answer 130

Plasma has lubricating effect that prevents too much contact between the potentially sticky blood cells and the endothelial cells lining the blood vessel wall This lubricating effect prevents unintentional blood cell adherence to vessel endothelial cell walls Healthy endothelial cells secrete anti adherence chemicals that help prevent all types of blood cells from adhering to them

Question 131

If platelets bind to the endothelial cells

Answer 131

They could adhere and trigger a coagulation (clotting) cascade Plasma lubrication and anti-adherence chemicals help prevent platelet adherence and possible intravascular blood clotting (thrombus formation)

Question 132

Interendothelial gaps

Answer 132

Allow the vessel to become more permeable allowing intravascular fluid (plasma) and WBCs to shift from intravascular to extra vascular (tissue) compartments These endothelial cells also stop producing anti adherence chemicals and may even start secreting chemicals that promote platelet and WBC adhesion to the blood vessel wall WBC adhesion important step in leukocyte infiltration into a wound site

Question 133

Result of histamine changes in endothelial cell function

Answer 133

Increased tissue fluid in wound site; edema + increased WBC infiltration; phagocytosis for wound healing

Question 134

Venules and histamine endothelial cell function

Answer 134

Venule endothelial cells gave lots of H1 receptors and are particularly sensitive to histamine Venules are considered the major vessels involved in the increased vascular permeability at wound site

Question 135

Myoendothelial contraction response

Answer 135

Very rapid, lasting 15-30 mins post injury

Question 136

Transient arteriole vasospasm/vasoconstriction

Answer 136

Is a stress response to tissue damage When histamine is released, the arteriole smooth muscle will switch to vasdilation

Question 137

Summary of Microvascular Response to Histamine

Answer 137

Tissue injury —> local tissue mast cells (degranulate and secrete) —> Histamine (binds to H1 histamine receptors on endothelial cells and vascular smooth muscle cells) —> Local microvascular responses —> 5 signs of inflammation

Question 138

5 cardinal signs of inflammation due to

Answer 138

Histamine induced microvascular endothelial and smooth muscle responses to tissue damage

Question 139

1) Local vasodilation at site of tissue damage

Answer 139

-Occurs as smooth muscle relaxes allowing arterioles to vasodilate and precapillary sphincters open -Local increased arteriole blood flow and increased blood hydrostatic pressure promotes passive capillary dilation within the wound site

Question 140

Benefits of local vasodilation at site of tissue damage

Answer 140

increased blood flow to the injured tissues —> increases nutrients and Proinflammatory mediators delivery to injured tissues, dilutes out causative agent, helps promote water removal and wound healing

Question 141

Physiological signs of local vasodilation at site of tissue damage

Answer 141

Redness, heat

Question 142

Local increased vascular permeability

Answer 142

-Occurs primarily in venules (minor effect on capillaries) —> actin —> endothelial cells contract aka become myoendothelial cells —> creates interendothelial cell gaps —> increases vascular permeability —> allows intravascular fluid (ie plasma) to enter damaged tissue resulting in increased interstitial (tissue) fluid volume

Question 143

Benefits Local Increased Vascular Permeability

Answer 143

Promotes movement of nutrients, WBCs, antibodies, and other proinflammatory mediators out of the blood plasma and into the wound site AND allows wbcs to infiltrate wound site to remove dead and damaged cells and pathogens from the site, promotes blood clot formation (if necessary) and promotes wound healing

Question 144

Physiological signs Local increased vascular permeability

Answer 144

Edema, pain, possible loss of function

Question 145

What two types of microvascular cells respond to histamine ?

Answer 145

Endothelial and smooth muscle cells

Question 146

What are the effects on the microvasculature in arterioles

Answer 146

Vasodilation

Question 147

What are the effects on the microvasculature in capillaries

Answer 147

Passive vasodilation slight stretch

Question 148

What are the effects of histamine on microvascularture venules

Answer 148

Constriction of endothelial cells =increased permeability

Question 149

Why is the vascular response important during acute inflammation

Answer 149

Brings nutrients and WBC’s, proteins to damaged tissues

Question 150

____ and ____ due to local arteriole vasodilation

Answer 150

Heat and redness

Question 151

____ due to increased local venule permeability causing excess tissue fluid accumulation

Answer 151

Edema

Question 152

___ and ___ due to pressure of the excess tissue fluid pushing on nerve endings and/or if pain inducing chemicals irritating local nerve endings

Answer 152

Pain and loss of function

Question 153

Edema is normally not visible within a tissue until a minimum of __% excess tissue fluid is present

Answer 153

30

Question 154

Edema definition

Answer 154

Defined as the excessive accumulation of fluid within the interstitial (tissue) spaces

Question 155

A tissue with excess tissue fluid is called

Answer 155

Edematous

Question 156

What is third spacing ?

Answer 156

Intravascular fluid has gone into the tissue = swelling = generalized Edema

Question 157

What is ascites?

Answer 157

Abdominal fluid accumulation Liver disease due to protein deficiency

Question 158

Types of edematous fluid

Answer 158

Transudate Exudate (2 subtypes, fluid exudate, cellular exudate)

Question 159

Capillary Exchange

Answer 159

The movement of fluid between blood plasma and interstitium by filtration or reabsorption

Question 160

The 2 pressures that promote filtration

Answer 160

-Blood/Capillary Hydrostatic Pressure (BHP) -Interstitial Fluid Osmotic (Oncotic) Pressure (IFOP)

Question 161

2 Pressures That Promote Reabsorption

Answer 161

-Blood/Capillary Colloid Osmotic (Oncotic) Pressure (BCOP) -Interstitial Fluid Hydrostatic Pressure (IFHP)

Question 162

4 Body Fluid Compartments

Answer 162

-3 are extracellular including 1) blood plasma 2) interstitial fluid 3) lymph -4th is the intracellular compartment -Fluid (water + solutes dissolved in the water) is constantly moving between these compartments because nutrients and waste exchange is a constant process

Question 163

Osmotic Pressure

Answer 163

-The pressure exerted by chemicals (especially proteins or sodium) found in a solution that pull/attract water towards them -i.e they promote osmosis (movement of water from high water area to lower water area) through a membrane -Osmotic pressure does not require a living/biological membrane to occur

Question 164

Oncotic Pressure

Answer 164

-Is the osmotic pressure exerted by colloids (proteins) in a biological solution, such as blood plasma or interstitial fluid -If discussing water/fluid movement from one compartment to another within a living body, Oncotic pressure is more direct but both terms are used interchangeably

Question 165

Fluid filtration

Answer 165

2 pressures promote Filtration of substances (water, nutrients) from blood plasma (I.e. intravascular) into tissue fluid (and then into the body cells)

Question 166

Reabsorption

Answer 166

2 pressures promote Reabsorption of substances from the tissue fluid (water, cellular waste products, cellular secretions) into the blood plasma

Question 167

Blood/Capillary Hydrostatic Pressure (BHP)

Answer 167

-Promotes filtration -Water P created by your blood pressure -Pushes fluid into tissues, allows nutrients to enter tissues

Question 168

Blood Colloid Osmotic/Oncotic Pressure (BCOP)

Answer 168

-Promotes Reabsorption -Proteins and ions (especially albumin and sodium) that exert osmotic P and pull fluid back into the blood -Normally helps prevent excess fluid build up in the tissues

Question 169

Interstitial Fluid Hydrostatic Pressure (IFHP)

Answer 169

-Promotes Reabsorption -Water P that is usually minimal but can increase dramatically during inflammation (due to edema)

Question 170

Interstitial Fluid Osmotic/Oncotic Pressure (IFOP)

Answer 170

-Promotes filtration -defined as the osmotic P exerted by colloids in interstitial fluid -usually minimal but if increased, the extra interstitial proteins exert osmotic P and pull water towards them, thus promotes increased tissue fluid (edema)

Question 171

Intracellular Osmotic P

Answer 171

-Normally equal to interstitial osmotic P, therefore cells retain normal morphology

Question 172

In Healthy Tissue Capillary Exchange

Answer 172

-More fluid is filtered than is reabsorbed -The excess tissue fluid is quickly drained away by the lymphatic system capillaries (about 3L/day) -No edema occurs -Normal role of the lymphatic system is to pick up excess tissue fluid and return that fluid (called lymph) to the blood stream

Question 173

Why are these 4 pressures important?

Answer 173

-When arterioles vasodilate and the capillary and venule endothelial cells increase their permeability THEY PROMOTE FILTRATION -The volume of tissue fluid increases dramatically and lymphatic drainage cannot always keep up = the excess tissue fluid stays in the tissue and edema occurs

Question 174

BHP pressure change during inflammatory response

Answer 174

BHP = increased pressure Cause of pressure change during inflammation: arteriole vasodilation increased blood flow into capillary bed

Question 175

IFOP pressure change during inflammatory response

Answer 175

-Increased pressure -Cause of pressure change during inflammation: Presence of microbial proteins, cell debris, and proinflammatory mediators in tissue fluid

Question 176

BCOP pressure changes during inflammatory response

Answer 176

-Decreased pressure (only one that does down/decreases -Cause of pressure change during inflammation: Normal: minimal effect -If liver disease/dysfunction: hypoalbuminemia -If kidney disease: Proteinuria

Question 177

IFHP pressure change during inflammatory response

Answer 177

-Increased pressure -Cause of pressure change during inflammation: arteriole vasodilation, increased venular vascular permeability, decreased lymphatic drainage

Question 178

Filtration increased movement into ____

Answer 178

Tissues/interstitial fluid

Question 179

Reabsorption increases fluid movement into ___

Answer 179

Blood stream/Blood plasma

Question 180

Edema always causes an increase in this pressure

Answer 180

IFHP

Question 181

Mechanisms of Edema Formation

Answer 181

-Decreased synthesis of plasma proteins (cirrhosis, malnutrition) Increased loss of plasma proteins (nephrotic syndrome) Increased plasma sodium and H20 retention (dilution of plasma proteins) —> Decreased capillary Oncotic pressure —> Edema -Increased capillary permeability (burns, inflammation) —> Loss of plasma proteins to interstitial space —> Increased tissue Oncotic pressure OR Decreased capillary onconic pressure —> edema -Lymph obstruction —> Decreased transport of capillary filtration protein —> Increased tissue onconic pressure -Increased Capillaru Hydrostatic pressure (venous obstruction, salt and water retention, heart failure) —> fluid movement into tissues —> edema

Question 182

Not all ___ is a result of inflammation

Answer 182

Edema

Question 183

More than 1 ___ can change in each situation

Answer 183

Pressure

Question 184

Clinical manifestations pressures Liver

Answer 184

Liver: Makes albumin, the major water regulator in blood plasma (regulates blood/capillary onconic P); decreased blood albumin causes decreased BCOP

Question 185

Clinical manifestations pressures Kidneys

Answer 185

Kidneys: any stressor will stimulate RAAS and increase aldosterone (regulates sodium and h20 retention by the kidneys); increased RAAS stimulation causes increased blood volume and increased BHP Extreme imbalance may also decrease BCOP if plasma proteins diluted out

Question 186

Clinical Manifestations Pressures Burns

Answer 186

Burns: Cause damage to microvasculature + inflammation —> massive fluid shifts into the tissues If blood proteins leak into the tissues, causes Increased IFOP

Question 187

Clinical Manifestations Pressure Infection

Answer 187

Infection: presence of microbial proteins + cell debris in interstitial fluid increase IFOP This pressure will increase even more as inflammatory mediators enter the wound site

Question 188

Clinical Manifestations Pressure Lymphatic Drainage

Answer 188

Lymphatic Drainage: damaged local lymphatic vessels, infections and cancer cells can block lymphatic drainage through lymph nodes When lymphatic drainage decreases, fluid accumulated in the tissues, causes increased IFHP

Question 189

Clinical Manifestations Pressure Hypertension

Answer 189

Hypertension: Leads to increased systemic BHP

Question 190

Clinical Manifestations Pressure Venous blood flow

Answer 190

Venous blood flow: obstruction leads to local increased venous BHP Eg. Varicose veins

Question 191

Clinical Manifestations Pressure Heart Failure

Answer 191

Heart failure: leads to pulmonary (if left heart failure) or systemic (if right heart failure) increased venous BHP

Question 192

Edematous fluid is more specifically called

Answer 192

Transudate or exudate

Question 193

Main differences effected transudate vs exudate

Answer 193

Timing of production Specific chemistry

Question 194

Why is excess tissue fluid important during inflammation?

Answer 194

-Purpose of inflammation is to dilute out injurious agents and bring in nourishment as well as WBCs to hopefully destroy foreign agents -The fluid and debris within the damaged site will eventually make its way into the lymphatic capillaries and ultimately enter a lymph node or the spleen to be destroyed by various innate and if stimulated by the specific antigen, adaptive WBCs, thus also promoting wound healing

Question 195

Transudate

Answer 195

-Immediate, excess watery tissue fluid -Essentially same chemical composition as normal tissue fluid produced during capillary exchange —> water, salts, electrolytes -Result of Increased local blood flow and increased local blood hydrostatic P (due to arteriolar vasodilation) -Most transudate is pushed out of dilated arterioles; capillaries have minor role -Helps dilute out injurious agent

Question 196

Exudate: Fluid exudate

Answer 196

-excess tissue fluid rich in plasma proteins -proteins help with innate and adaptive immune responses —> may contain antibodies, complement, clotting factors, cytokines to aid in pathogen destruction and wound healing

Question 197

Cellular exudate

Answer 197

-include the wbcs that infiltrate the injury site (in clotting, also includes platelets and rbcs) -wbc phagocytosis of causative agent and cell debris aids in destroying pathogens and in wound healing

Question 198

Exudate

Answer 198

-Takes longer to begin, requires myoendothelial contraction to occur -Most exudate flows out of venules since they have largest interendothelial cell gaps and greatest increased vascular permeability; capillaries have minor role -Thicker consistency

Question 199

Normal Production of transudate and/or exudate: BHP

Answer 199

-Pressure of the blood plasma within a blood vessel, essentially water pressure -Within the microvasculature, BHP is normally highest in arterioles and lowest in venules, so blood naturally flows in this direction -BHP is a pushing pressure that pushes fluid out of the capillaries into the interstitium (tissue fluid) to nourish body cells

Question 200

Normal Production of transudate/exudate: BCOP

Answer 200

-Pressure of the plasma proteins to pull water towards them -BCOP is a pulling pressure; pulling water towards the blood plasma chemical exerting osmotic pressure, albumin (most abundant plasma protein) and sodium

Question 201

Production of Transudate: Edema due to increased BHP varicose veins

Answer 201

-E.g due to obstruction of venous drainage (vericose veins) varicose veins damage venous valves and cause congestion of blood in the systemic veins. Local venous BHP increases and pushes fluid into the tissues leading to peripheral edema, especially common in the legs

Question 202

Production of transudate: Edema due to increased BHP Congestive heart failure

Answer 202

-CHF occurs when the heart muscle is too weak to pump blood effectively -Also causes congestion of blood in either pulmonary or systemic veins -Similar to obstructed venous outflow, that increased venous pressure causes back pressure to the microvasculature, increased venous BHP and pushes fluid into tissues

Question 203

Production on Transudate: Edema due to increased BHP Hypertension

Answer 203

-Dramatic increase in arterial BP causes increased BHP in the arterioles and capillaries -Thus more fluid is pushed into tissues at the arteriole end of the capillary bed than can be reabsorbed at venule end of microvasculature

Question 204

Production of Transudate Edema due to decreased blood colloid osmotic/Oncotic pressure (BCOP)

Answer 204

-Eg liver or kidney disease -Liver makes majority of your plasma proteins including albumin (albumin is a major regulator of water balance in blood plasma; exerts blood colloid pressure which means it pulls water towards it) -Hypoalbuminemia causes a decrease in the osmotic pressure of albumin = Transudate fluid stays in the tissues causing peripheral Edema and leading to a decrease in blood volume -Some kidney disorders result in a loss of plasma proteins into the urine, again leading to peripheral Edema

Question 205

Production of Exudate: What happens during acute inflammation

Answer 205

-During acute inflammation, due to rapid histamine mediated vascular response, local arteriole vasodilation causes increased local blood flow into the injury site -This increases local capillary BHP -Increased local BHP will push fluid from the blood into the tissues —> Transudate forms, then the endothelial cells contract, increasing venule and capillary vascular permeability allowing larger proteins to enter the interstitium -= fluid exudate forms once the WBCs enter the wound site —> then cellular exudate forms

Question 206

Transudate Vs Exudate what makes them

Answer 206

Transudate if epithelial contraction DIDNT happen, pushing excess fluid into tissues, lymphatic system can’t keep up IFHP increases swelling Exudate increase IFHP but also increased vascular permeability = cells/wbcs/proteins escape

Question 207

Cause of Edema: increased BHP

Answer 207

Composition of fluid in tissue space: Transudate Local or systemic effects or both: Local and systemic Eg increased bp

Question 208

Cause of Edema: Deceased BCOP

Answer 208

Composition of fluid in tissue space: Transudate Local or Systemic effects or both: Systemic (number of blood proteins decrease but not escape)

Question 209

Cause of Edema: Increased Vascular Permeability

Answer 209

Composition of Fluid In Tissue Space: Transudate or Exudate (Eg inflammation Local or Systemic: Both

Question 210

Cause of Edema: Decreased lymphatic drainage

Answer 210

Composition of fluid in fluid space: Transudate or exudate depending on situation Local or systemic: both

Question 211

Lewis’s Triple Response

Answer 211

-Illustrates the dermal microvasculature response to tissue injury that occur IMMEDIATELY (within 1-2 secs) -Within several seconds: Histamine release by mast cells = The flush, The flare, The wheal

Question 212

Lewis Triple Response Vasospasm

Answer 212

-When a tissue is injured, 2 smooth muscle vascular effects occur in quick succession: -Arteriolar vasospasm - immediate but brief as vascular smooth muscle contracts in response to sympathetic NS release of norepinephrine or epinephrine = transient vasoconstriction stress response to injury = white line -Vasospastic response is quickly overwhelmed by the much larger mast cell degranulation and release of histamine -= Arteriolar vasodilation - histamine mediated smooth muscle relaxation = vasodilation = redness + heat -Venular increase vascular permeability -histamine mediated myoendothelial contraction = swelling

Question 213

The Flush

Answer 213

-Red line -Due to onset of local arteriole (and passive) capillary vasodilation = occurs within seconds

Question 214

The Flare

Answer 214

-Bright red zone surrounding the red line -Due to larger area of local arteriole vasodilation = Takes 15-20 seconds

Question 215

The Wheal

Answer 215

-Swelling at the site -Due to fluid shift of intravascular fluid into tissues -Caused by increased vascular permeability of local venules -Takes 1-3 mins

Question 216

Why is triple response normally preceded by white line ?

Answer 216

Tissue injury hurts, it’s a stress response by SNS

Question 217

White line, Erythema, Edema Time frame, Cause, Mediator

Answer 217

White line; 1-2 seconds, SNS stimulated, quickly overwhelmed by mast cell degranulation and release of histamine Erythema: 15-30 secs, Vasodilation of local arterioles, histamine Edema: 1-3 seconds, increased vascular permeability, histamine

Question 218

Immune cells include

Answer 218

-all WBCs -whether they reside in the tissues (mast cells and resident macrophages or dendritic cells) or in the blood stream (basophils, eosinophils, neutrophils, monocytes, b & t lymphocytes, NK cells)

Question 219

Mast cells and basophils

Answer 219

-secrete histamine and other Proinflammatory mediators

Question 220

Peripheral WBCs, platelets, RBCs, damaged endothelial cells or damaged parenchyma cells and any foreign invaders

Answer 220

-Can all release a variety of proinflammatory chemicals that act as chemotactic agents (distress signals), vasodilatiors, pain inducers or affect vascular permeability

Question 221

WBCs destroy pathogens using

Answer 221

Phagocytosis, making antibodies

Question 222

RBCs transport

Answer 222

Oxygen and carbon dioxide

Question 223

Platelets trigger blood

Answer 223

Coagulation/clots

Question 224

Innate Immune cells

Answer 224

Macrophages Neutrophils Dendritic cells Mast cells Basophils Eosinophils NK cells

Question 225

Adaptive immune cells

Answer 225

Lymphocytes, B/T

Question 226

Function Innate immune cells

Answer 226

First line of defence, identify , initiate specific adaptive immune response

Question 227

Functions adaptive immune cells

Answer 227

Destroy invading pathogens, make antibodies

Question 228

WBC’s that promote inflammation

Answer 228

-Mast cells -Basophils -Neutrophils

Question 229

WBCs that act as phagocytes

Answer 229

-Neutrophils -Macrophages (monocytes derived) -Dendritic cells -B lymphocytes —> plasma cells -NK cells -Eosinophils (also secrete histaminase)

Question 230

WBCs that induce cell apoptosis my

Answer 230

-NK cells -Eosinophils -Cytotoxic T lymphocytes (cell mediated immunity) -Aided by antigen presenting cells and helper t lymphocytes

Question 231

WBCs that boost innate and adaptive responses

Answer 231

-Helper T Cells (boost everybody)

Question 232

Surveillance cells of the Mononuclear Phagocyte System

Answer 232

-Includes innate WBCs that are located at common sites of entry of pathogens Eg. Epidermal/dermal and mucosal surfaces -Eg. Dendritic cells within dermis/epidermis and mucous membranes -Eg. Various fixed macrophages (usually M1 that reside in specific tissues) and wandering macrophages that tour the lymphatic system, blood stream and reside and function in specific tissue or organ

Question 233

Specific Macrophages That reside In Organs

Answer 233

-Kupffer cells in the liver -Microglia in the brain -Dust cells in the lungs

Question 234

How do WBCs recognize tissue damage?

Answer 234

-Innate immune cells have receptors that recognize and react to specific microbial membrane protein patterns or microbial by products or even chemicals released by own damaged body cells

Question 235

Apoptosis

Answer 235

-Programmed cell death -Part of normal cell physiology -Due to lack of use such as extra uterine smooth muscle cells after baby is born -Or due to inflammatory response = targeted cell death due to the release of cytolytic enzymes by various WBCs

Question 236

APCs

Answer 236

-Antigen presenting cells -Phagocytize, process, and present antigen fragments (pieces of antigen attached to a cell membrane protein called MHC) to cytotoxic T cells of the adaptive immune system -If the cytotoxic T cell has a receptor that can bind to the antigen (TCR= T cell receptor) it will bind then attack the APC, release apoptotic enzymes thus destroying the antigen =cellular mediated immunity

Question 237

Development of Immune Function

Answer 237

-Born with some innate WBCs such as intravascular neutrophils and tissue mast cells but very few adaptive immune cells -Adaptive immune function minimal at birth -Begins to truly develop around 6 months, fully functional by 2 years of age -By 1 year most children have fairly good immune response to infection

Question 238

More boosters =

Answer 238

More memory B cells = stronger/faster antibody response

Question 239

PMN

Answer 239

-Polymorphonuclear leukocytes -I.e neutrophils

Question 240

The cellular response; Mast cells and Other immune cells

Answer 240

-While the mast cells are busy degranulation get and synthesizing Proinflammatory mediators to stimulate the inflammatory response in the tissues, other immune cells traveling in the blood stream need to enter the tissues to help

Question 241

Distress Signals

Answer 241

Other WBCs also respond to distress signals Eg. Neutrophils, dendritic cells, and macrophages also have receptors that allow them to respond to chemicals released by injured, dead, or dying body cells and some microbial proteins

Question 242

Pus

Answer 242

-Made of a combination of dead and dying WBCs (mainly neutrophils), dead and dying body cells, and dead and dying bacteria

Question 243

WBC Response During Acute Inflammation

Answer 243

-WBCs respond to: 1) Increased Vascular Permeability 2) Injured Cell Distress Signals

Question 244

WBCs response to increased vascular permeability

Answer 244

-Increased vascular permeability causing slower local venule blood flow -Slow blood flow allows WBCs to enter plasmatic zone —> adhere to endothelium —> WBC margination/pavement action —> diapedesis —> emigration —> cellular exudate produced

Question 245

WBC response to injured cell distress signals

Answer 245

-Cytokines and chemokines that promote WBC chemotaxis and infiltration into injury site

Question 246

Purposes of WBCs in wound site?

Answer 246

Phagocytosis or apoptosis of pathogens and cell debris —> destroy pathogens and promote healing

Question 247

During acute inflammation all 3 ___ cells will be affected by change in blood flow

Answer 247

-Blood cells -As fluid leaks out of blood stream the local blood viscosity increases and local rate of blood flow slows down -Rather than anti adhesion molecules, local endothelial cells start expressing cell adhesion molecules on their outer cell membranes -Slower local blood flow allows time for blood cells to enter plasmatic zone, adhere to endothelium and then infiltrate damage site and help in the inflammatory response

Question 248

Phagocytosis

Answer 248

-Ingestion and enzymatic and/or peroxide digestion of cell debris, foreign material, microbes -AIDS inflammatory response by removing causative agents and debris which promote would healing -Function of most WBCs

Question 249

Apoptosis

Answer 249

-Programmed cell death via the use of cytolytic chemicals such as proteolytic granzymes and perforins -Destroy the integrity of the targeted cells plasma membrane and the cell dies -Used by innate NK cells and adaptive cytotoxic T cells and eosinophils

Question 250

WBC emigration into wound site is mediated by:

Answer 250

-Chemotaxis -WBCs, especially neutrophils, respond immediately to a chemical trail of distress signals from damaged tissues

Question 251

Chemotaxis

Answer 251

-The directional movement of leukocytes in response to a chemical gradient (a chemoattractant) -Common chemotactic agents: cell debris, microbes, proinflammatory chemokines and cytokines

Question 252

Margination (and Pavementation)

Answer 252

-Mechanism by which WBCs move to outer margins of vessels (into plasmatic zone), roll/tumble along the endothelium, adhere to endothelium -Pavement the endothelium by binding to endothelial cell adhesion molecules, CAMS, made only during inflammatory response

Question 253

Diapedesis

Answer 253

-Mechanism by which WBC squeeze into wound site through the inter-endothelial gaps -Gaps created when histamine stimulated myoendothelial contraction -An amoeboid movement (flowing of cytoplasm against cell membrane, aided by cytoskeletal motility proteins, actin)

Question 254

Emigration

Answer 254

-The actual movement of WBCs from the intravascular to the extravascular space -I.e wound site -They follow the chemotactic trail right to the damage

Question 255

WBC emigration process takes

Answer 255

10 minutes

Question 256

Recognition and attachment of WBC to microbial chemicals of bacterium (CAMS)

Answer 256

-CAMS are cell adhesion molecules made by phagocytes in response to microbial chemicals or damaged cell products -Help with WBC motility and with phagocytosis of the correct cell (I.e. those that should be eaten in the wound site) -Some of these adhesion molecules are the cellular receptors WBCs use to recognize microbial or body cell chemicals: PRRs and PAMPs -Other foreign proteins (antigens) and microbial proteins attached to antibodies as well as some complement proteins (C3b) also stimulate phagocytic cells to marginate, infiltrate the wound site, and then adhere to and ingest the cells/chemicals that need to be removed from the wound site

Question 257

% of neutrophils in blood

Answer 257

60-70

Question 258

Cytokines vs chemokines

Answer 258

Cytokines = communication between WBCs Chemokines = alerts to something wrong

Question 259

What type of exudate is resultant of leukocyte infiltration/emigration into the wound site ?

Answer 259

Cellular exudate

Question 260

Adherence, Margination, and Diapedesis

Answer 260

1) WBC adherence to endothelial cells (notice endothelial cell contraction) 2) WBC margination and pavementation —> begin diapedesis 3) Diapedesis continues —> WBC emigration into wound site

Question 261

Chemotaxis, infiltration/emigration and phagocytosis

Answer 261

1) Chemotaxis - positive Chemotaxis as WBCs follow the chemotactic trail towards the wound site = help signal WBCs (ie they promote leukocyte infiltration) 2) Lots of WBCs (neutrophils here) have migrated/infiltrated the wound site 3) Phagocytosis occurs

Question 262

Leukocyte Emigration (aka leukocyte infiltration)

Answer 262

-Movement of WBCs from the blood into the damaged tissue site -Controlled by chemotactic agents “distress signals” released by damaged cells, including damaged vascular endothelial cells, damaged parenchymal cells, and microbial chemicals -Since the WBCs move toward the chemotactic agents, process is sometimes called positive Chemotaxis and the chemicals called Chemoattractants -Running from the smell of a skunk is negative chemotaxis -The WBCs are essentially blood hounds that follow the chemical scent to the damage site -Neutrophils have the best nose to scent out distress chemicals and usually the first WBC to emigrate into the wound and arrive in large numbers -Neutrophils have very short lifespans often only minutes and often become distress signals themselves -lots of dead neutrophils in pus

Question 263

Apoptosis is used by

Answer 263

Innate NK cells, adaptive cytotoxic T cells, and eosinophils

Question 264

NK cells kill

Answer 264

Pathogenic cells and damaged body cells

Question 265

TC cells use

Answer 265

-Apoptosis to specifically kill “marked” cells = cells with unique foreign markers on their outer cell membrane -Viral infected cells displaying foreign/viral Ag markers -Antigen presenting cells (APCs) that have previously phagocytize and processed antigens into small fragments that are displayed on the outer cell membrane of phagocytic WBC -TC cells bind to the antigen fragments, secrete cytolytic enzymes and destroy the entire APC -Cancer cells with unique foreign antigen/tumour markers

Question 266

Eosinophils kill

Answer 266

-Parasites by apoptosis -Also phagocytize and destroy antigen-antibody complexes

Question 267

Unsuccessful Phagocytosis: Tonsils

Answer 267

-In some people, macrophages living in tonsils become breeding grounds for bacteria such as pustule forming streptococcus -Tonsils will need to be removed -Happens when phagocytosis is not successful =chronic infection

Question 268

Platelet response occurs if

Answer 268

Blood vessel wall is damaged during injury, are they bleeding

Question 269

Platelets respond to

Answer 269

1) Loss of endothelial cells due to blood vessel wall damage —> allows platelet-collagen interaction —> platelet activation occurs 2) Slower/more viscous blood flow —> resulting from increased vascular permeability during inflammatory response —> allow platelets to adhere to damaged blood vessel wall

Question 270

Platelet activation includes

Answer 270

Platelet adherence —> platelet release reaction —> platelet plug formation —> Hemostasis

Question 271

Purpose of platelet activation

Answer 271

Initiate hemostasis and blood coagulation to prevent further blood loss

Question 272

Platelets respond to tissue damage by

Answer 272

Initiating hemostasis and if necessary blood clotting

Question 273

Hemostasis

Answer 273

Defined as the stoppage of blood flow (to prevent excessive bleeding)

Question 274

Blood Coagulation

Answer 274

Formation of thrombus (if intravascular clot) or blood clot (if extravascular clot)

Question 275

Components of blood clot

Answer 275

Platelets, sticky fibrin threads and trapped RBCs

Question 276

Inflammation and platelet activation collagen

Answer 276

-Endothelial damage and resultant inflammation can trigger platelet activation -In an inflamed blood vessel there is a lack of endothelial anti adhesion proteins and increased vascular permeability -Platelets can enter the plasmatic zone and adhere to the endothelium -Where endothelial cells are damaged, platelets may interact with collagen -Since collagen is a connective tissue component located directly outside of the endothelium, platelet-collagen interaction in a damaged vessel is expected

Question 277

Inflammation and platelet activation slowed blood

Answer 277

-During inflammation, increased vascular permeability, especially at the venule end of the capillary causes a slight decrease in the blood pressure in the venule -This slows the rate of blood flow allowing platelets time to enter the plasmatic zone -Increases the chance of platelet-collagen interaction and platelet activation -Activated platelets become sticky, try to plug the wound in the vessel wall and stimulate blood clot formation -Since tissue damage often includes damage to blood vessels and bleeding, blood clot formation is an important part of the acute inflammatory response

Question 278

All blood vessels are lined with ..

Answer 278

-Endothelial cells (tunica intima) -Regardless of the size of the blood vessel, directly beneath the intimal endothelium there will always be connective tissue -Means there will always be the protein collagen

Question 279

What NSAID blocks thromboxane A2

Answer 279

ASA = anticoagulant because it blocks thromboxane synthesis

Question 280

Platelet Plug Formation: 1 Platelet adhesion

Answer 280

1) Platelet adhesion - Damage to endothelial lining —> platelet contact collagen —> platelets adhere to vessel wall endothelium

Question 281

Platelet Plug Formation: 2 Platelet Release Reaction

Answer 281

-Platelets secrete prothrombotic chemicals that make them enlarge and become “sticky” including PDGF, serotonin, thromboxane A2, ADP -ASA would block thromboxane

Question 282

Platelet Plug Formation: 3 Platelet Aggregation

Answer 282

-Platelets may successfully plug the wound and stop the bleeding by forming a platelet plug -If still bleeding now you need coagulation (clotting) cascade

Question 283

Thrombocytopenia/Thrombocytosis

Answer 283

Thrombocytopenia = patients bleed longer Thrombocytosis = probe to dangerous intravascular thrombotic events

Question 284

RBC’s Respond to … during acute inflammation

Answer 284

1) Slower local blood flow —> resulting from increased venule vascular permeability during inflammatory response and/or 2) Platelet activation

Question 285

RBC activation includes:

Answer 285

RBC adherence —> Rouleaux formation —> followed by extravasation (RBCs move into extravascular spaces)… bleeding into tissues —> RBCs help form extravascular blood clot

Question 286

Purpose of RBC response

Answer 286

Help limit blood loss by strengthening and stabilizing blood clot

Question 287

RBC Response During Acute Inflammation

Answer 287

-During acute inflammatory response, increased vascular permeability increases tissue fluid causing blood remaining in local vascularture to thicken a bit -This slower, thicker blood flow allows RBCs to enter plasmatic zone, RBCs may begin to stack up and then spill out of the vessel where they become trapped in a blood clot that was triggered by the platelets

Question 288

Rouleaux

Answer 288

The stacking up process

Question 289

Extravasation

Answer 289

-Process of blood cells leaving a blood vessel -Extravasated RBCs will be trapped by the proteinaceous clotting fibers called fibrin threads and become part of the blood clot -Form bruises and hematomas -During wound healing they will need to be removed with some proteinaceous enzymes (Eg plasmin) and the help of hungry macrophages

Question 290

Initial transient arteriolar vasoconstriction due to autonomic sympathetic NS release of

Answer 290

Epinephrine/Norepinephrine

Question 291

Plasma protein systems

Answer 291

-complement system -clotting system -kinin system -these are cascades of pro-inflammatory proteins that because activated during tissue damage -pre formed proteins (made in advance) are circulating in the blood plasma as soluble inactive proteins

Question 292

What happens if plasma proteins fail

Answer 292

-if one or more proteins in insufficient or fails to activate, cascade fails leading to a lesser effect of that acute phase protein system in inflammatory response -will delay or even prevent a proper acute inflammatory response allowing causative agent to survive and cause further damage/blood loss

Question 293

Defective protein synthesis is the result of —- or —- Etiology

Answer 293

Congenital, Genetic

Question 294

Lack of clotting protein is a cause of

Answer 294

Hemophilia

Question 295

What are the plasma protein systems?

Answer 295

-3 interrelated groups of Proinflammatory plasma proteins —> activated by tissue damage —> cascade effect -Part of fluid and cellular exudate -Part of inflammatory soup/cytokine storm -Part of acute phase proteins

Question 296

Fluid exudate includes

Answer 296

Transudate plus proteins = fluid exudate includes the proteins of the 3 plasma protein systems (still present in cellular exudate)

Question 297

Since plasma proteins are activated during acute inflammatory responses they are also called

Answer 297

Acute phase proteins or acute phase reactants

Question 298

Other acute phase proteins include:

Answer 298

Chemokines and cytokines and systemic inflammatory marker called C-reactive protein (CRP)

Question 299

All proteins are produced when specific

Answer 299

Genes are turned on (expressed) and protein synthesis occurs -over expression of a gene could cause overproduction of a particular protein which could cause exaggeration of that particular plasma protein pathway

Question 300

General Characteristics Plasma Protein Systems

Answer 300

-Produced by liver and/or WBCs -Most produced in advance; circulate in blood plasma as inactive proenzymes -Peak activity 10-40 hours post tissue damage

Question 301

How do plasma proteins work (mechanism of activation)

Answer 301

When tissue damage occurs —> inactive circulating proenzymes —> convert to active enzymes —> cascade of enzyme activation —> promote inflammatory response

Question 302

How plasma proteins act as Proinflammatory mediators

Answer 302

-Support and maintain the histamine response -Help prevent further blood loss -Part of acute phase proteins/reactants

Question 303

If you need more plasma proteins..

Answer 303

1) WBC’s release cytokines (interleukins IL-1 or IL-2) —> stimulate liver to produce more and or/ 2) Produced in situ by damaged body cells (ie chemokines) 3) If systemic issue C reactive protein

Question 304

Inactive protein proenzyme prevents

Answer 304

Unnecessary, potentially harmful enzymatic activation within healthy tissues such as the liver cells or WBCs in which they are produced

Question 305

In response to tissue damage inactive proenzymes …

Answer 305

-enter the injured tissues, become activated enzymes (the enzymes are proteases that change the protein structure of the next inactive enzyme in the pathway and catalyze/speed up different proinflammatory chemical reactions such as signalling more WBCs, promoting blood clotting or maintaining vascular responses) -Tissue damage will initiate the enzymatic activity of one or more components of a particular system -Once the first protein in a particular plasma protein system is activated, domino effect occurs resulting in activation of remaining proteins of that system

Question 306

Plasma proteins have_____ functions

Answer 306

Overlapping Safety net to ensure that inflammatory response is successful

Question 307

Complement proteins stimulated by

Answer 307

Inflammatory response to bacterial and yeast infections and by Ag-Ab reactions

Question 308

Clotting proteins stimulated by

Answer 308

Damage to vascular wall ie bleeding

Question 309

Kinin proteins are stimulated by

Answer 309

Microvascular response to tissue damage, acts like a weak histamine

Question 310

Inflammatory mediators (aka inflammatory markers) can be measured in

Answer 310

Blood plasma Their specific levels and types help determine severity of inflammation

Question 311

Increase complement proteins =

Answer 311

Bacterial, yeast infection, or Ag-Ab response; local or systemic inflammatory response

Question 312

Increase clotting proteins =

Answer 312

Microvascular damage, local or systemic inflammatory response

Question 313

Increase CRP

Answer 313

Systemic inflammatory response

Question 314

The complement system

Answer 314

-Innate immune response (2nd line of defence) -Series of 9 plasma proteins (C1-C9) -Source: liver

Question 315

Complement system mechanism of activation

Answer 315

-3 pathways of complement protein activation (require some type of causative agent) 1) Classical pathway - antibody present 2) Lectin pathway - bacterial polysaccharide (mannose) present 3) Alternative pathway - bacteria lipopolysacharides or yeast carbohydrates present

Question 316

If inactive/active

Answer 316

Inactive = proenzyme: C1, C3 Active = functional enzyme: C1a, C3a, C3b

Question 317

C1-C9 means

Answer 317

Complement protein is inactive

Question 318

C1a-C9a means

Answer 318

This protein is now active and triggering activation of the next complement protein in the pathway

Question 319

If proenzyme is cleaved into 2 parts

Answer 319

Both are active

Question 320

Physiological effects of complement protein activation

Answer 320

-Form membrane attack complexes (MAC); C5b-C9 destroy cell membrane of causative agent -Act as opsonins (opsonization); C3b to make tasty -Act as leukocyte chemotactic agents; attract phagocytes to site (WBC infiltration) = promote phagocytosis; C5a -Act as anaphylatoxins - stimulate mast cell degranulation —> histamine release; C3a or C5a; part of anaphylaxis -Attract antibodies to wound site; C1a

Question 321

End result of complement activation

Answer 321

Promote inflammation and help destroy pathogens

Question 322

Membrane Attack Complex (MAC)

Answer 322

-C5b-C9 -Complement protein complex pokes holes in the outer cell membrane of the bacterium leading to cytolysis -E.g makes bacterial walls leaky to water —> bacteria lysed/contents leak out —> bacterium dies

Question 323

Opsonization

Answer 323

-C3b -This complement protein will sugar coat the surface of the antigen to be phagocytized helping to attract phagocytes and make the process of phagocytosis more efficient

Question 324

Chemotactic agents and anaphylatoxins

Answer 324

-C3a and C5a -Promote WBC infiltration -Especially attract phagocytic neutrophils, macrophages and dendritic cells to damage site and stimulate rapid mast cell degranulation = histamine release -Histamine then stimulates inflammatory response

Question 325

The coagulation (blood clotting) system

Answer 325

-A group of 12 plasma proteins (factors I-XIII; active Xa -aka clotting factors -Sources; liver (major) and as required by platelets or other damaged cells

Question 326

Coagulation system mechanism of activation

Answer 326

1) -Endothelial damage occurs —> platelet-collagen interaction in damaged blood vessel —> platelet activation 2) Blood flow stasis —> platelet activation -platelet activation leads to sequential activation of clotting factors of the coagulation cascade —> sticky fibrin threads form -RBCs and platelets trapped in sticky fibrinous mesh —> blood clot forms

Question 327

End result of clotting factor activation

Answer 327

Hemostasis to stop the bleeding

Question 328

The clotting system is part of the process called

Answer 328

Hemostasis

Question 329

Why is Hemostasis including the clotting system involved during acute inflammation

Answer 329

-Tissue injury often involves damage to the blood vessels in the area (bruise, cut) -When a blood vessel is damaged, RBCs spill out of the vessel = extravasation -Platelets become activated, as the process of Hemostasis occurs to try to prevent excessive blood loss

Question 330

2 Routes to Activation of the Clotting Cascade

Answer 330

1) Extrinsic Pathway 2) Intrinsic Pathway

Question 331

Extrinsic Pathway Clotting Cascade

Answer 331

-More common pathway, cuts/bruises -Tissue damage stimulate/activates -released by damaged parenchymal and stromal cells = release tissue factor (TF, Factor III) -TF (IIIa) —> Factor X activated (Xa)—> Common pathway of Coagulation triggered

Question 332

Intrinsic Route clotting Cascade

Answer 332

-Activated by factors in blood; Endothelial cells damage (Eg. Arteriosclerosis, phlebitis, arteritis)—> platelet-collagen interaction —>Platelet activation —> Factor XII activated (Xa) —> coagulation cascade -XII—>XIIa—>Xa—> Common Pathway of Coagulation

Question 333

Common Pathway of Coagulation

Answer 333

Xa—> Prothrombin (II) —> Thrombin (IIa) Fibrinogen (I) —> Sticky Fibrin (Ia) Threads —> Blood Clot (Coagulation)

Question 334

FP =

Answer 334

-Fibrinopeptides -Cleaved (I.e. cut) from fibrinogen -Chemotactic for neutrophils and increase vascular permeability (by increasing kinin effects)

Question 335

Both intrinsic and extrinsic pathways meet at the

Answer 335

Common pathway of coagulation initiated by Factor X (Xa) and ending with the conversion of the inactive soluble protein Fibrinogen (proenzyme) to active insoluble Fibrin threats

Question 336

Fibrin threads form…

Answer 336

Sticky mesh work of a blood clot

Question 337

___ and ____ stick to the mesh work

Answer 337

Platelets and RBCs Create a larger plug to hopefully stop the bleeding

Question 338

Endothelial damage allows ___ and ____ to interact

Answer 338

Platelets and CT collagen

Question 339

Clot should remain until

Answer 339

-Wound healing is well underway

Question 340

Clot Dissolution

Answer 340

-The enzymatic (via plasmin) digestion of fibrin + macrophage phagocytic destruction of old trapped RBCs and platelets that occurs during wound healing

Question 341

Factor XII

Answer 341

-Hageman Factor -XII denotes (indicates) inactive clotting factor -XIIa denotes the active clotting factor

Question 342

Cofactors required for blood clotting include

Answer 342

-Ca -K

Question 343

The coagulation cascade is a ____ feedback system

Answer 343

-Positive -since clotting mechanisms continue either until the bleeding has stopped or supply of clotting proteins is exhausted

Question 344

Blood clotting disorders are a result of

Answer 344

-an inability to produce one or more biologically active clotting factor -common inherited form of hemophilia is due to genetic defect in production of factor VIII -Dietary or nutrient absorption issues with calcium or decrease liver production of Vit K can also impede

Question 345

Clotting factor 1

Answer 345

Fibrinogen -Source: Liver Pathway of activation: Common

Question 346

Clotting Factor 2

Answer 346

Prothrombin -Source: Liver -Pathways: Common

Question 347

Clotting Factor 3

Answer 347

Tissue Factor (Thromboplastin) -Source: Damaged Tissues and Activated Platelets Pathways: Extrinsic

Question 348

Clotting Factor 10

Answer 348

Stuart Factor, Prower Factor, Thrombokinase -Source: Liver -Pathway: Extrinsic and Intrinsic

Question 349

Clotting Factor 12

Answer 349

Hageman Factor, Glass Factor, Contract Factor or Antihemophilic Factor C -Source: Liver -Pathway: Intrinsic

Question 350

Clotting Factor 4

Answer 350

Calcium -Source: Diet, Bones, Platelets -Pathway: All

Question 351

Fibrinogen is the

Answer 351

Last inactive factor to be activated but more obvious clotting pathway

Question 352

If ends in Ogen/Pro =

Answer 352

Inactive form

Question 353

Factor _ must be activated to start clotting

Answer 353

10

Question 354

Extrinsic = Intrinsic =

Answer 354

Bruising, cuts / DVT

Question 355

If trigger XIIa

Answer 355

Activates kinin system

Question 356

Components of a blood clot or thrombus

Answer 356

-RBCs -Platelets -Fibrin threads

Question 357

Thrombus

Answer 357

Denotes intravascular blood coagulation (intrinsic pathway)

Question 358

Blood clot

Answer 358

Denotes extravascular blood coagulation Eg bruise, hematoma, contusion (extrinsic + intrinsic pathway)

Question 359

Trigger that starts the cascade

Answer 359

Slowed blood, interaction with collagen

Question 360

Functions of a Blood Clot

Answer 360

1) Plug damaged vessels to stop further bleeding 2) Trap microbes to prevent spread of infection 3) Provide a framework for wound healing

Question 361

Fibrous Network =

Answer 361

A mesh like collection of sticky fibrin threads

Question 362

Colours of a bruise/hematoma

Answer 362

Correspond to the breakdown of the hemoglobin in the extravasated RBCs as they are phagocytized by Macrophages

Question 363

Colours of bruises

Answer 363

Red (acute inflammation) —> black —> blue —> green —> yellow

Question 364

Clot dissolution

Answer 364

Once wound healing is complete and damaged blood vessel have new intact endothelial PLASMIN will dissolve the blood clot by breaking up fibrin threads -local MACROPHAGES Will chew up the clot components that were trapped within tissue cells

Question 365

The Kinin System

Answer 365

-Group of 4 Plasma Proteins -Source: Liver (major) and many other body cells -Mechanism of Activation; Tissue damage (Prekallikrein is activated by Factor XIIa of clotting cascade —> bradykinin)

Question 366

Kinin helps maintain…

Answer 366

The inflammatory response

Question 367

Physiological effects of kinins

Answer 367

-Bradykinin has similar but less potent effects than histamine -Arteriole vasodilation—> redness, heat - Increased vascular permeability—> Edema -Acts as Chemotactic agent for WBCs -Pain stimulant (works with prostaglandins to irritate nerve endings)

Question 368

Factor __ activated prekallikrein

Answer 368

Factor XII aka Hageman factor -activated prekallinkrein in Kinin pathway = creation of bradykinin

Question 369

Bradykinin stimulates

Answer 369

Vascular smooth muscle relaxation and myoendothelial cell contraction

Question 370

Kinin cascade and ___ have interrelated functions

Answer 370

-clotting cascade -chances are if inflammatory response is occurring, blood vessel is also damaged and bleeding is present

Question 371

Kinin cascade activated by

Answer 371

-XIIa Factor of clotting system XIIa —> prekallikrein —> Kallikrein —> Kininogen —> Bradykinin —> histamine effects and pain

Question 372

Activation of Kinin pathway can trigger

Answer 372

XIIa and Factor XIIa can trigger Kinin pathway

Question 373

Secretions that contain Kinin

Answer 373

Tears, sweat, saliva, urine, feces Help mediate local inflammatory response

Question 374

Inflammatory regulators/anti-inflammatories

Answer 374

Carboxypeptidase, Kinase, Plasmin, Histtaminase

Question 375

Why are inflammatory regulators/anti inflammatory chemicals needed

Answer 375

Once problem has been resolved and the tissue begins to heal, anti-inflammatory signals must be present to turn off secretions of pro-inflammatory histamine, complement, clotting and Kinin proteins and to release any trapped RBCs and platelets by dissolving fibrin threads

Question 376

Inflammatory regulators made by

Answer 376

Usually enzymes Made by the liver, endothelial cells, immune cells and/or healing body cells

Question 377

Inflammatory regulators also know as

Answer 377

Proteolytic enzymes

Question 378

Carboxypeptidase

Answer 378

Effects C3, Inactivates anaphylatoxic C3a and C5a (leukocyte/neutrophil migration)

Question 379

Kinase

Answer 379

Inactivates Kinin pathway

Question 380

Plasmin

Answer 380

Lots of anti inflammatory effects Activated form of inactive plasma protein plasminogen made by endothelial cells, monocytes, macrophages

Question 381

Plasmin activity

Answer 381

Anticoagulant - decreases activation of factor XIIa and thrombin thus effects both intrinsic and common pathways of coagulation, limits size of clot, and involved in clot dissolution (aka fibrinolysis = destruction of blood clots) destroys fibrin threads that trap platelets and RBCs Decreases complement activity (turns of C3, occurs once Ag-Ab complexes in damaged tissues have been cleared by eosinophils; decreases rate of WBC infiltrations and phagocytic activity, helps decrease histamine levels

Question 382

Histaminase

Answer 382

Made by eosinophils that enter wound site, Inactivates histamine remaining In tissue fluid at end of inflammatory response

Question 383

Effects of over production of complement proteins

Answer 383

Excessive inflammation and histamine secretion —> hypersensitivity reaction

Question 384

Effects of Overproduction of clotting proteins

Answer 384

Hypercoagulability

Question 385

Effects of overproduction of Kinin proteins?

Answer 385

Excessive inflammation —> hypersensitivity reaction and pain

Question 386

Inflammatory soup contains

Answer 386

ALL chemical mediators found in fluid and/or cellular exudate that promote inflammation including plasma derived mediators and cell derived mediators

Question 387

Inflammatory soup is

Answer 387

Fluids only no solids = Fluid exudate (proteins)

Question 388

What’s in inflammatory soup

Answer 388

1) Plasma Derived Mediators -Includes 3 plasma protein systems (complement, clotting, kinin and CRP) 2) Cellular Derived Mediators -Local parade one or autocrine effects -Made by a variety of WBC’s, platelets, endothelial cells and/or injured cells activated by tissue damage -Includes cytokines and chemokines -chemicals made by cells but NOT cells themselves -All Proinflammatory mediators may become part of soup during inflammatory response, they are part of fluid/cellular exudate

Question 389

Cytokine Storm

Answer 389

When damaged tissues and the immune system create too many cytokines and chemokines, inflammation can overwhelm the tissues causing extensive tissue damage Eg. Covid 19 and lung damage

Question 390

Inflammatory soup =

Answer 390

Cytokine storm -Issue with cytokine storm name is that it does not include other proinflammatory chemicals (chemokines, acute phase proteins, even histamine) but they are also present and causing excessive inflammatory damage

Question 391

How are cytokine storms treated

Answer 391

Antihistamines

Question 392

Prolonged inflammatory response =

Answer 392

Systemic effects such as Fever Leukocytosis (increased production of leukocytes) Increased plasma levels of specific cytokines and CRP

Question 393

Vascular, cellular and protein responses to tissue damage present in both ___ and ___ clinical manifestations

Answer 393

Local, and/or systemic

Question 394

Local Manifestations of Acute Inflammation

Answer 394

-Extent will depend on severity of tissue damage -5 Cardinal signs of inflammation will be present to some degree Type of local inflammatory fluid : presence of transudate, fluid exudate, or cellular exudate depends on location and cause of damage

Question 395

Types of Local Inflammatory Exudate

Answer 395

1) Serous Exudate 2) Fibrinous Exudate 3) Purulent/Suppurative Exudate 4)Hemorrhagic Exudate

Question 396

Serous Exudate

Answer 396

Thin, Clear, Straw-coloured, watery fluid, similar to Transudate (minimal proteins) Small amount normal during inflammation (Eg blister), copious amounts not normal = infection possibly

Question 397

Fibrinous Exudate

Answer 397

Contains lots of proteins such as fibrin and fibrinogen, thick/viscous, usually lots of fibrin

Question 398

Fibrinous vs fibrous

Answer 398

Do not confuse Fibrous tissue contains excess collagen Eg a scar

Question 399

Purulent/Suppurative Exudate

Answer 399

Contains pus, abscesses or cysts may be present, infected

Question 399

Purulent/Suppurative Exudate

Answer 399

Contains pus, abscesses or cysts may be present, infected

Question 400

Hemorrhagic exudate

Answer 400

Significant bleeding occurred, contains thick gel like coagulated blood (blood clots)

Question 401

Hemorrhagic exudate

Answer 401

Significant bleeding occurred, contains thick gel like coagulated blood (blood clots)

Question 402

Serous fluid found in

Answer 402

A) characterized by copious effusion (excess tissue fluid accumulation) of watery fluid with very little protein -found in early inflammatory response or in mild injury such as a blister -if clear and pink may be called serosanguinous exudate B) Pleurisy = inflammation of pleural membranes = causing serous fluid buildup in pleural cavity = atelectasis = lung collapse

Question 403

Fibrinous Exudate means

Answer 403

Large amount of protein is present in exudate Occurs with more severe injury resulting in large increase in vascular permeability which allows plasma proteins to pass through large interendothelial cell gaps in blood vessels and deposit in tissues Since fibrin is protein that creates clotting fibers, excess fibers create coagulated exudate that covers surface of area such as body cavity (pericarditis, pleurisy, pneumonia, peritonitis)

Question 404

Clinical significance Fibrinous Exudate

Answer 404

Body cavities and internal organs are surrounded by serous membrane that secrets thin watery lubricating serous fluid, Fibrinous Exudate impairs normal ability of organs in cavaities to move freely as the function = in pericarditis heart can’t pump properly

Question 405

What are pustules?

Answer 405

Pus filled blisters/ lesions

Question 406

Pus forming bacteria are called

Answer 406

Pyogenic Eg. Staphylococchus

Question 407

Pus may become ..

Answer 407

Walled off in a cyst or abscess = must be evacuated in order for wound healing to occur

Question 408

Term for removal of Purulent exudate

Answer 408

Evacuation

Question 409

Hemorrhagic exudate means

Answer 409

Blood vessels have ruptured, bleeding has occurred and a blood clot is present Contains extravasated blood cells, clotting factors (platelets, RBCs, fibrin)

Question 410

Effects of inflammation on lymphatic system local

Answer 410

If tissue is bleeding, small lymphatic vessels have also been damaged Part of time it takes swelling to go down is time it takes to heal lymphatic capillaries so they can start draining excess tissue fluid and lymph away from tissues

Question 411

Effects of inflammation on lymphatic system systemic

Answer 411

Because lymph capillaries are more permeable than blood capillaries, they often are conduits for spread of infection or neoplastic cells = reason that regional lymph node biopsy is completed for suspected cancer

Question 412

Key points of inflammation on lymphatic system

Answer 412

Locally, lymphatic vessels and organs can also be damaged by direct mechanical trauma (acquired Etiology)

Question 413

Lymphatic capillaries are ___ so they can pick up excess ___

Answer 413

Leaky, tissue fluid -makes them excellent conduits of transport

Question 414

Lymphatic capillaries may become inflamed due to

Answer 414

1) local or systemic spread of infections 2) blockage by neoplastic cells (metastasis)

Question 415

Lymphedema

Answer 415

Excessive swelling of tissue due to blockage or loss of lymphatic flow (decreased lymphatic drainage) -caused by last slide

Question 416

Clinical manifestations of lymphatic tissue inflammation

Answer 416

Lymphadenopathy Lymphadenitis Lymphangitis

Question 417

Lymphadenopathy

Answer 417

-Enlarged lymph node or nodes -palpable swelling of 1 or more lymph nodes with little or no tenderness/pain -Eg. Upper resp infection with enlarged cervical lymph nodes -Eg. Lymphoma or Cancer metastatic lymph node involvement

Question 418

Lymphadenitis

Answer 418

Painful, inflamed lymphadenopathy (enlarged lymph nodes) Usually due to infection Shows signs of inflammation (redness, tenderness) -Eg. Tonsillitis -E.g infectious mononucleosis (Epstein-Barr virus)

Question 419

Lymphangitis

Answer 419

Inflammation of lymphatic vessel due to infectious or non infectious causes Follows direction of lymph drainage (towards heart) Watch for red streaks radiating towards heart High risk of systemic infection

Question 420

Systemic manifestations of acute infection indicate

Answer 420

Tissue damage/infection is spreading to other body regions

Question 421

Major systemic manifestations acute inflammation

Answer 421

1) fever (pyrexia) -pyrogens present 2) leukocytosis - increased WBC count 3) increase acute phase reactant proteins in blood plasma 4) increase in CRP in blood plasma 5) may also include: malaise, drowsiness, poor appetite, increase liver production of fibrinogen, decrease liver production of albumin, hypotension

Question 422

Fever stimulated by

Answer 422

Stimulated by pyrogens tricking thermoregulatory centres of hypothalamus

Question 423

Leukocytosis

Answer 423

Increased number of WBCs -during systemic acute inflammatory response to infection 2-3 fold increase of WBC count may occur (some WBC such as eosinophils are rare

Question 424

Differential WBC count

Answer 424

-Used to detect change in number of rare WBCs such as eosinophils -Determines % of each subtype of plasma WBC within total plasma WBC population - increased neutrophils = acute inflammation -Increased monocytes = chronic inflammation -Increased lymphocytes = viral infection -Increased eosinophils = parasitic infection or large number of Ag-Ab complexes present

Question 425

Acute Phase Reactant Proteins and systemic acute inflammation

Answer 425

Fine oven levels increase if bleeding is occurring Albumin production decreased as liver spends it resources on acute inflammatory protein production Since albumin major regulator of intravascular fluid volume (BCOP) during capillary exchange, blood volume decreased as fluid enters tissues = loss of blood volume = hypotension

Question 426

What is used to diagnose inflammatory disease

Answer 426

Body T Differential WBC count Inflammatory protein plasma markers

Question 427

Fever (pyrexia)

Answer 427

Elevation of core body temp above hypothalamic set point of 37C

Question 428

Pyrogens

Answer 428

-Fever inducing chemicals that can change hypothalamic T set point -2 Types Endogenous pyrogens, Exogenous pyrogens

Question 429

Purpose of fever?

Answer 429

To inhibit bacterial growth

Question 430

Complications of fever

Answer 430

-tissue damage to cellular proteins (denaturation) -Increase bacterial endotoxin associated tissue damage -Increased demand for 02 and glucose -Dehydration, lethargy, malaise, hypotension, rapid HR

Question 431

Body T is controlled in the

Answer 431

Hypothalamus of the brain Specifically in the hypothalamic thermoregulatory Center -senses changes in temp of blood and CSF flowing in the hypothalamus

Question 432

Endogenous Pyrogens

Answer 432

-Cell derived cytokines (IL-1, TNF) made by neutrophils and macrophages after exposure to tissue damage or antigen-antibody complexes -Elliot a fever response

Question 433

Exogenous Pyrogens

Answer 433

-Bacterial lipopolysaccarhides (LPS), bacterial exotoxins, bacterial endotoxins that are released as bacteria are destroyed, viral proteins, ag-Ab complexes, some drugs

Question 434

Course of Fever

Answer 434

1) release of pyrogens (exo or endo) 2) pyrogens trick hypothalamus into thinking core body temp is too LOW = hypothalamus responds by stimulating shivering to 3) INCREASE body temp thus 4) higher body temp that manifests as fever 5) treatment of pyrogens means that either WBCs are busy phagocytize for those pyrogens microbes or you take fever reducing drug = decreased pyrogens in your blood 6) hypothalamus notices you are too hot and 7) starts physiological mechanism of sweating that reset thermostat back to normal

Question 435

If INCREASE in pyrogens in your blood/CSF

Answer 435

Hypothalamus thinks your cold = you shiver and your body heats up

Question 436

If decrease pyrogens in blood/csf

Answer 436

Hypothalamus thinks ur too hot, you sweat and body cools down

Question 437

Fever also increases

Answer 437

Oxygen consumption by hot tissues = increased HR Could be detrimental in a cardiac patient whose body cannot tolerate increased work load

Question 438

Leukocytosis systemic

Answer 438

-Diagnosed by differential WBC count -Acute inflammation: Increase number of circulating phagocytes (neutrophils, monocytes) Increase number of tissues phagocytes (macrophages and dendritic cells Increase number of specific WBC determined by infective agent

Question 439

Increased acute phase plasma proteins systemic acute inflammation

Question 440

Possible outcomes of acute inflammation

Answer 440

Chronic inflammation occurs when the combined efforts of the vascular, cellular and plasma protein responses have not successfully cleared the causative agent

Question 441

Major immune cell types chronic inflammation

Answer 441

Lymphocytes (long enough to trigger adaptive immune response) and macrophages Fibroblasts also present since chronic inflammatory sites are prone to excessive scar tissue formation

Question 442

Chronic inflammation is stand-off between

Answer 442

Host defences and causative agent

Question 443

Chronic inflammation essentially

Answer 443

An unsuccessful acute inflammatory response

Question 444

Etiology Chronic Inflammatory Response

Answer 444

Continuous presence of causative agent: -Infection: Chronic tonsillitis, tuberculosis, HIV, Hep C -Foreign body: shrapnel, asbestosis -Foreign Antigen: tissue/organ transplant rejection, allergy (hypersensitivity) reactions -Self antigen: autoimmune reactions Repetitive injury -Osteoarthritis, repetitive strain injuries, carpal tunnel syndrome, workplace chemical exposure

Question 445

Chronic Inflammatory response and scarring problem

Answer 445

Weaker than normal tissue, prone to reinjury

Question 446

Chronic inflammation or chronic inflammatory response develops when

Answer 446

Vascular (Lewis’s triple) response, innate and adaptive immune cellular response, plasma protein activations could not destroy and remove cause of tissue damage

Question 447

Within Chronic inflammatory site…

Answer 447

There will be areas of new acute inflammation and areas of various stages of wound healing

Question 448

Things that increase chance of chronic. Inflammation

Answer 448

Age (very young/old), immunocompromised, hypersensitivity immune reaction to repeat exposure, virulence of infectious agent, strength and duration of toxic exposure, repetitive reinjury