Lecture 2 and 3 objectives Flashcards
(128 cards)
1
Q
list the disease etiologies
A
Microorganisms, hypoxia/ischemia, nutritional deficiencies, trauma/surgery, radiation, caustic chemicals, extreme heat or cold
2
Q
What is the first line of defense?
A
skin and mucous membranes (tears, saliva, gut flora, stomach acid)
3
Q
What is the second line of defense?
A
inflammatory response (nonspecific, acute inflammation is an expected response to injury)
4
Q
What is the third line of defense?
A
immune reponse
5
Q
When does immediately transient response occur?
A
following a minor injury, active for a few minutes or hours (slap to the face)
6
Q
When does immediate sustained occur>
A
following a major injury, vascular, and active for a few days because more extensive damage has occurred (pathogen response while blistering)
7
Q
When does a delayed hemodynamic occur?
A
approximately 4-24 hours after an injury (Sun burn)
8
Q
What do vascular changes in the acute inflammation process entail?
A
increased blood flow to the injury site and increased blood vessel permeability at the injury site
9
Q
What two major anatomic changes happen in vascular response?
A
vasodilation, increased permeability
10
Q
What are the benefits of increasing permeability during the vascular response?
A
helps plasma and cells get to the site of injury while also making it difficult for infectious agents o move away from the injury site-prevents the spread of the foreign/offending agents
11
Q
How does increased permeability occur?
A
endothelial cells that are lining the vessels contract, separating the intercellular junction
12
Q
What marks the start of the cellular response
A
Movement of phagocytic white blood cells into the area of injury
13
Q
How long does it take neutrophils to arrive to site of injury? How long can they survive?
A
arrive within 90 minutes. They survive approximately 10 hours
14
Q
Benefits of neutrophils arriving to scene?
A
Causes increase in circulating WBCs, immature forms of neutrophils may be released
15
Q
what is leukocytosis?
A
increase in numbers of WBC
16
Q
When do Eosinophils pull up?
A
Allergic reactions and parasitic infections
17
Q
When do basophils pull up? what do they do?
A
inflammation and allergic reactions, release histamine, bond with IgE
18
Q
When do Mast Cells pull up? What do they do?
A
Similar to basophils, but in Connective Tissue. Found in mucosal surfaces-lung, GI tract, dermis. They’re in the Sentinel position. Allergic reaction, parasitic infections. Also bond with IgE
19
Q
When do monocytes pull up?
A
approximately 24 hours after injury
20
Q
Characteristics of Monocytes
A
Largest WBCs, significantly longer lifespan than PMNs, arrive 24 hours after injury, they are the predominant cell in injury cite approximately 48 hours after injury, engulf larger and greater quantities of foreign material than neutrophils, play a role in adaptive immune response
21
Q
List the four steps in cellular response
A
Margination/adhesion
Migration (diapedesis)
Chemotaxis
Phagocytosis
22
Q
What happens during margination/adhesion
A
injury causes relapse of chemical mediators (cytokines)
Increased expression of adhesion molecules (selectins)
Leukocytes slow migration and begin marginating (pavementing) along periphery of vessels
Adhesion to vessel walls allows us to advance to the next step
23
Q
What happens during diapedesis?
A
Leukocytes extend pseudopods and pass through the capillary wall via ameboid movement
24
Q
What happens during chemotaxis?
A
Leukocytes travel through the tissue to the site of injury
Cytokines and complement (cytokines are released by damaged cell)
25
What happens during Phagocytosis?
Recognition and attachment +opsonization
engulfment
intracellular killing
26
What is the most important kinin in the inflammatory response?
Bradykinin
27
What functions does bradykinin have?
Vasodilation and increased permeability, smooth muscle contraction, involved with pain response
28
what are kinins broken down by?
kininase and angiotensin-converting enzyme
29
Key protease enzyme in the clotting process?
Thrombin
30
What are fibrinopeptides and thrombin functions?
Expression of endothelial adhesion molecules, production of prostaglandins, PAF, and chemokines
31
Where are complements found?
They're present in inactive form in plasma
32
What do complement proteins do once activated?
Activated to become proteolytic enzymes that degrade other complement proteins in a cascade
33
what are some complement functions?
Vasodilation, increased vascular permeability, smooth muscle contraction, leukocyte activation, adhesion, and chemotaxis, augmentation of phagocytosis, and mast cell degredation
34
Most important complements
C3a, C5a
35
What cells release histamines?
mast cells, basophils, and platelets?
36
Histamine functions
one of the first mediators of inflammation, major role in vascular inflammatory response via the H1 receptor, Increase vasodilation, increase vascular permeability
37
List of cytokines (5)
chemokine, interferons (IFNs), interleukins (ILs), lymphokines, and tumor necrosis factor (TNF)
38
what are two cytokines that are major mediators of early inflammatory response?
Interleukin-1 and Tumor necrosis factor-alpha
39
what are IL-1 and TNF-alpha responsible for?
fever, adhesion of leukocytes to vessel epithelial, chemotaxis, and acute phase response. Also involved in pain response.
40
What is arachidonic acid?
a fatty acid precursor
41
where is arachidonic acid derived from?
phospholipids in the cell membrane
42
What is arachidonic acid a precursor for?
prostaglandins, leukotrienes, thromboxane
43
what is derived from the cyclooxyrgenase pathway?
prostaglandins and thromboxane
44
what is derived from the lipooxygenase pathway?
leukotrienes
45
What are prostaglandins responsible for?
vascular permeability and vasodilation, involved in pain response, also makes Prostaglandin E1, and Prostaglandin E2 (both induce inflammation and potentiate effects of other inflammatory mediators, especially histamine, thromboxane A2-promotes platelet aggregation and vasoconstriction
46
What inhibits the cyclooxygenase pathway for prostaglandin and thromboxane synthesis?
NSAIDS and Aspirin
47
What do PGE1 and PGE2 do?
induce inflammation and potentiate effects of other inflammatory mediators, especially histamine
48
What does Thromboxane A2 do?
promote platelet aggregation and vasoconstriction
49
What do leukotrienes do?
similar function to histamine
vascular permeability, adhesion of endothelial cells, chemotaxis, further histamine release
Slow reacting substance of anaphylaxis (SRS-A) group of leukotrienes-causes slow and sustained constriction of bronchioles
50
What are the leukotriene receptor antagonists used for?
used for the treatment of asthma
51
what blocks the lipoxygenase pathway from synthesizing leukotrienes
5-lipoxygenase inhibitor
52
Where are platelet activating factors derived from ?
cell membrane phospholipids
53
What is the function of Platelet activating factor?
induces platelet aggregation, stimulates platelets to release vasoactive mediators and synthesize thromboxane, increased vascular permeability, neutrophil activation, chemoattractant for eosinophils
54
What does nitric oxide do?
Smooth muscle relaxation, antagonism of platelet functions (adhesion, aggregation, degranulation), reduction of leukocyte recruitment, assists in microbicidal action by phagocytes
55
Lymphadenitis etiology
inflamed lymph nodes that are draining an injured area, caused by the filtering lymph fluid that contains infectious or necrotic material form the local, injured/infected area.
(free and non moving lymph node: not good-can be cancer)
56
Etiology of lymphangitis
inflammation of infection of lymph channels draining in an injured area.
Entire lymph vessel is inflamed and points to the site of injury
57
Pathogenesis of lymphadenitis
Swollen, tender, mobile/moving, rubbery, may be erythematous, or fluctuant
58
Pathogenesis of lymphangitis
MCC streptococcus pyogenes and appears as red, tender streaks that extend proximally
59
Treatment of lymphadenitis or lymphangitis
antimicrobial therapy, anti-inflammatories, analgesics, cool compress
60
What happens in Erythrocyte sedimentation rate?
increased levels of acute-phase proteins, especially fibrongen, causes an increase in the erythrocyte sedimentation rate
61
C-reactive protein
binds to surface of invading microorganisms to assist their destruction
also aids with regulating immune response, clearance of necrotic cells
can help diagnose or measure activity of inflammatory or autoimmune disease
elevated CRP is associated with increased cardiovascular disease risk
62
what conditions can cause an elevation in C-reactive protein?
hypertension, diabetes, smoking, aging, obesity, depression,
63
what is an elevated C-reactive protein count indicative of?
inflammation
64
what are the 5 cardinal signs of inflammation?
erythema, heat, swelling, pain, loss of function
65
what cases erythema?
vasodilation
66
what causes heat to be a cardinal sign of inflammation
blood is warm
67
what causes swelling?
increased vascular permeability and increased fluid in extracellular space
68
what causes pain in inflammation?
compression in tissue due to swelling; direct elicitation of pain due to inflammatory mediators
69
what causes loss of function from inflammation?
direct damage to tissue from injury, decreased function due to pain and swelling
70
5 major types of shock
cariogenic, hypovolemic, anaphylactic, neurogenic, septic
71
what are the three types of distributive shock
anaphylactic, septic, neurogenic
72
what causes cardiogenic shock?
inability of heart to pump the required amount of blood. caused by cardiac arrhythmias, damaged heart muscle or valves, pressure around heart inhibiting cardiac movement, rupture of heart muscle
73
what causes hypovolemic shock?
deceased intravascular volume leading to decreased perfusion of vital organs. Can be caused by hemorrhage or fluid loss
74
What causes septic shock?
systemic vasodialtion secondary to infection and dysregulation of inflammatory response
75
what largely mediates septic shock?
Interleukin 1 and tumor necrosis factor alpha
76
what causes anaphylactic shock?
severe, rapid allergic or hypersensitivity reaction with potential to be fatal
77
What causes neurogenic shock?
damage to the autonomic pathways within the CNS
78
How does septic shock affect the circulatory system?
severe hypotension and hypo perfusion
excessive vasoactive mediators, decreasing vascular reisstance
third spacing of fluid, increased vascular permeability
79
How does septic shock affect the lungs?
Pulmonary edema and hypoxia
80
how goes septic shock affect the GI tract?
increased intestinal permeability allowing bacteria and bacterial endotoxins in gut to enter systemic circulation
81
how does septic shock affect the liver
impaired elimination of bacteria and endotoxins from gut due to direct cellular injury
82
how does septic shock affect the kidney?
impaired filtration of toxins and waste products from blood due to hypo perfusion and direct renal damage
83
how does septic shock affect the nervous system?
encephalopathy due to changes in cell signaling caused by inflammatory mediators dysfunction of blood-brain barrier
84
four steps of tissue repair in terms and the approximate time table
1. hemostasis (right away)
2. inflammation (approx 90 min)
3. proliferation
4. remodeling
85
what does hemostasis include?
clotting, vascular response
86
what does proliferation include?
epithelial healing, scar formation
87
what does remodeling include?
scar remodeling includes decrease in fibroblasts, decrease in blood vessels, increase in collagen
88
what are the three possible outcomes of scar remodeling
resolution, regeneration, replacement
89
when does resolution occur?
very mind injury, with minimal disruption (rapid healing, minimal to no scaring)
90
when does regeneration occur?
primary with labile or stable cell types
cells can either:
proliferate (reproduce and grow)
differentiate (local cells mature and become specialized)
Diapedesis may occur (local similar cells migrate to replace lost or damaged cells)
91
What happens during replacement?
production of scar tissue when regeneration is not possible (usually seen in injuries to permanent cells, extensive or major injuries)
92
List the four types of growth factors
Vascular endothelial growth factor
Platelet derived growth factor
fibroblast growth factor
Epithelial growth factor
93
what do the growth factors do?
mediate proliferation, differentiation, and cell metabolism, mediate inflammatory response, promote chemotaxis of leukocytes and fibroblasts, stimulate angiogenesis, contribute to generation of ECM
94
What types of cells produce vascular endothelial growth factor?
oxygen deficient cells
95
what are the 4 major steps of angiogenesis
1. Proteolytic degradation of parent vessel basement membrane (capillary sprout forms)
2. Migration of endothelial cells from parent vessel towards the angiogenic stimulus
3. Proliferation of endothelial cells behind the leading edge of migrating cells
4. maturation of endothelial cells and vessel walls
96
what is angiogenesis?
formation of new capillaries
97
what is diapedesis?
cells moving from the blood vessels to the tissue
98
What are interns?
transmembrane proteins that allow for attachment to the ECM and communication between intracellular and extracellular environments
99
What do fibroblasts do in respect to wound healing?
Fibroblasts secrete collagen, produce growth factors that encourage the healing process, help convert provisional matrix to granulation tissue, lay down new collagen during remodeling process
100
What do endothelial cells do in respect to wound healing?
aid in re-epitheliazation and laying down new borders of the epithelium between the wound and external environment, also important in angiogenesis
101
what do macrophages do in respect to wound healing?
remove foreign matter and invading organisms, extracellular debris, damaged fibrin and cell fragments
they release growth factors to stimulate cell growth, fibroblast attraction and angiogenesis
also help convert the provisional matrix to granulation tissue
102
What does collagen do in respect to wound healing?
aid in the remodeling of scar tissue
103
What affects healing process?
type of tissue damaged, extent of injury, underlying host factors, age, foreign bodies, blood flow and oxygenation
104
What is parenchyma tissue? + an example
functioning cells of an organ or body part?
(IE myocyte, hepatocyte, nephron)
105
what is stromal tissue? + an example
connective, supportive framework that supports the function of the parenchymal tissue
(IE connective tissue, extracellular matrix)
106
What are labile cells? + an example
cells that continually divide and replicate
(IE epithelial cells- skin, oropharynx, GI tract, Bone marrow)
107
what are stable cells? +an example
normally stop dividing when growth ceases, but can regenerate when given appropriate stimulus
must have supporting stromal framework to regenerate properly
(IE hepatocytes, smooth muscle cells)
108
What are permanent cells +an example
Cannot regenerate or divide
(IE neurons, cardiac myocytes, ocular lens)
109
What is Vitamin C used for?
collagen
110
What are the systemic manifestation of chronic inflammation?
fever, malaise, fatigue, anemia, anorexia (weight loss)
111
Explain the pathogenesis of chronic granulomatous inflammation and associated diseases and distinguish it from granulation tissue.
+Nodular inflammatory lesions that encase substance that are not easily destroyed by usual inflammatory and immune responses
-Foreign bodies or pathogens
+Macrophages adapt to address the foreign body
-Giant cells (multinucleated, surround large particles) or epithelioid cells (surround and contain the offending agent and the macrophages processing it)
+Fibrous tissue eventually surrounds and encapsulates the inflamed area: macrophages phagocytize harmful substances within granuloma and fill with necrotic remains to limit the foreign material from spreading to the rest of the body
112
Explain how chronic inflammation causes disease in terms of the cellular mechanisms, cytokine effects, and tissue pathology.
Nonspecific chronic inflammation:
-Diffuse accumulation of macrophages and lymphocytes at the site of injury
-Cytokines produced leads to persistent chemotaxis of leukocytes/fibroblasts
-Significant scar tissue forms and replaces normal stromal/parenchymal tissues -This causes loss of normal structure/function of tissue
n in the body by blocking ferroportin which carries RBC, this causes anemia
-IL-1, TNF-alpha and IFN-gamma also play a role in inhibiting erythropoietin release and augmenting RBC phagocytosi
113
Explain how chronic inflammation causes disease in terms of the cellular mechanisms, cytokine effects, and tissue pathology.
+Cancer and inflammation:
-Inflammatory response to abnormal or damaged cells. Tumor cells often have abnormal markers and outgrow their supply of nutrients which leads to cell distress/ischemia
-Cytokine response leads to angiogenesis and influx of new nutrients
-Growth factors promote reproduction of cancer cells and new vessels
-Proteases and ECM remodeling enhances ability to grow and spread
114
Explain how chronic inflammation causes disease in terms of the cellular mechanisms, cytokine effects, and tissue pathology.
+Anemia and inflammation:
-Prolonged inflammation leads to IL-6 production which increase hepcidin by the liver
-Hepcidin reduces iron in the body by blocking ferroportin which carries RBC, this causes anemia
-IL-1, TNF-alpha and IFN-gamma also play a role in inhibiting erythropoietin release and augmenting RBC phagocytosis
115
Types of plasma proteins?
Complement proteins, kinins, and clotting system
116
What is involved in pain response?
cytokines, prostaglandins, bradykinins
117
what release histamines?
Mast cells, basophils, and platelets
118
What stops cell membrane phospholipids from making arachidonic acid?
corticosteroid medication
119
what are chemical mediators?
cytokines
120
list out the types of cytokines
chemokine, interferons, interleukins, lymphokines, and tumor necrosis factor
121
list out inflammatory mediators
plasma proteins, histamine, interleukin and other cytokines, platelet activating factor, prostaglandins, leukotrienes.
122
where are c-reactive proteins made?
liver
123
where are fibrinogens created?
liver
124
what is granulation tissue made up of?
new capillaries, proliferating fibroblasts, and residual inflammatory cells
125
What do fibroblasts secrete for ECM components?
fibronectin, hylauronan, proteoglycans, and collagen
126
what are proteins used for?
needed for mediation of inflammatory phase, fibroblast proliferation, collagen synthesis, angiogenesis, and remodeling
127
what are carbohydrates used for?
needed for energy for WBCs and reduce use of proteins for energy
128
What are fats used for?
needed for synthesis of new cells
