Gen Path Exam 1 - Cell Injury/Death, Inflammation, Wound Healing, and Hemostasis Flashcards
1
Q
Give examples of continuously dividing tissue
A
Skin, mouth, vagina, cervix, GI, exocrine ducts
2
Q
Give examples of stable tissue that divide only in response to injury
A
Endothelial cells, fibroblasts, SM, solid organs (kidney, liver, pancreas)
3
Q
Give examples of permanent tissue that never proliferate after birth
A
Neurons, heart muscle, skeletal muscle
4
Q
Name endogenous causes of stress/injury
A
Hypoxia (most common)
Immunologic rxns
Genetic abnormalities
Aging
5
Q
Name exogenous causes of stress/injury
A
Toxins (pollutants, asbestos, cig smoke)
Infectious pathogens
Nutritional imbalance
Physical agents (trauma)
6
Q
Increase in size of cell and organ
A
Hypertrophy
7
Q
Occurs in cells with limited capacity to divide (ex: skeletal muscle)
A
Hypertrophy
8
Q
Give an example of physiologic hypertrophy
A
Uterus during pregnancy
9
Q
Give an example of pathologic hypertrophy
A
Heart during hypertension
10
Q
Increase in # of cells (controlled)
A
Hyperplasia
11
Q
Occurs in tissue capable of division
A
Hyperplasia
12
Q
Give an example of physiologic hyperplasia
A
Breast development (hormonal)
Liver regeneration (compensatory)
13
Q
Give an example of pathologic hyperplasia (caused by excessive hormonal or growth factor stimulation)
A
Endometrial hyperplasia
Benign prostatic hyperplasia
14
Q
Decrease in size of cells
A
Atrophy
15
Q
Loss of cell substance by decreased protein synthesis or increased protein degradation
A
Atrophy
16
Q
What are the causes of atrophy?
A
Decreased workload, blood supply, and endocrine stimulation
Inadequate nutrition
Aging
17
Q
One cell type replaced by another cell type
A
Metaplasia
18
Q
New type may better withstand stress, but can predispose to malignant transformation
A
Metaplasia
19
Q
Give an example of metaplasia
A
Ciliated columnar cells become stratified squamous in bronchi of smokers
20
Q
Disordered growth
A
Dysplasia
21
Q
Division of precancerous cells, may be reversible, but may progress to cancer
A
Dysplasia
22
Q
Failure of cell production in embryogenesis
A
Aplasia
23
Q
Decrease in cell production in embyrogenesis
A
Hypoplasia
24
Q
Describe the tolerance for ischemia without irreversible injury for:
Neurons
Heart cells
Skeletal muscle
A
Neurons = 3-5 mins
Heart cells = 1-2 hrs
Skeletal muscle = hrs
25
When stress exceeds cell's adaptive ability
Cell injury
26
What are the 4 types of cell injury in this course?
Hypoxia
Oxidative stress
Reversible
Irreversible
27
Oxygen deficiency
Hypoxia
28
Examples of hypoxia
Lung disease
Anemia
29
Specific type of hypoxia
Ischemia
30
Reduced blood supply leads to oxygen deficiency (ex: blocked artery)
Ischemia
31
ATP needs _______ and cell metabolism needs ________
oxygen; ATP
32
Induced by reactive oxygen species
Oxidative stress
33
Oxygen derived free radicals
Reactive oxygen species
34
Chemically unstable, attack nucleic acids, proteins, and lipids
Free radicals
35
What do small amounts of reactive oxygen species normally result from?
Respiration and energy production
36
What do reactive oxygen species do normally? Where are they produced?
Destroy microbes
Produced in phagocytic leukocytes
37
Accumulation of reactive oxygen species is BAD. When does this happen?
Radiation
Exogenous chemicals
Inflammation
38
What mechanisms are there to minimize injury by reactive oxygen species?
Free radical scavengers
Anti-oxidants
39
Name the 3 free radical scavengers
Superoxide dismutase
Glutathionine peroxidases
Catalase
40
Block formation of free radicals and scavenge after they have been formed
Anti-oxidants
41
Can be exogenous or endogenous
Anti-oxidants
42
Name 4 anti-oxidants
Vitamins E, A, C
Beta carotene
43
What are the mechanisms of injury by reactive oxygen species?
Membrane damage
DNA damage
Protein cross-linking
44
Normal function/morphology returns when stimulus leaves
Reversible cell injury
45
What is the most common change in reversible cell injury?
Cellular swelling
46
Cells can't recover and will die
Irreversible cell injury
47
What are the main causes of irreversible cell injury?
Loss of mitochondrial function
Loss of structure/function of membranes
Loss of DNA/chromatin structural integrity
48
What can happen to the nucleus during cell death?
Condensation (pyknosis)
Fragmentation (karyorrhexis)
Dissolution (karyolysis)
49
What are the 2 different mechanisms of cell death?
Necrosis
Apoptosis
50
Describe necrosis
Cell membranes fall apart
Enzymes leak out and digest cell
Inflammation
Messy
Damages surrounding cells
51
Describe apoptosis
Programmed cell death
Cell shrinks
Nucleus condenses and fragments
Apoptotic bodies fall from cell and removed by macrophages
NO inflammation
52
Which necrosis?
Caused by infarct in solid organs; does NOT occur in brain
Coagulative necrosis
53
Which necrosis?
Tissue looks firm
Coagulative necrosis
54
Which necrosis?
Cell outlines preserved, NO NUCLEUS, eosinophilic (pink)
Coagulative necrosis
55
Which necrosis?
Caused by bacterial/fungal infections and hypoxia in CNS
Liquefactive necrosis
56
Which necrosis?
Dissolution of tissue into viscous liquid
Liquefactive necrosis
57
Which necrosis?
Ischemia of limb
Gangrenous necrosis
58
Which necrosis?
Coagulative necrosis -> looks like mummified tissue
Can have superimposed liquefactive necrosis
Gangrenous necrosis
59
Which necrosis?
Caused by TB infections because body tries to wall off infection
Caseous necrosis
60
Which necrosis?
Cheese-like, friable yellow/white necrotic tissue
Caseous necrosis
61
Which necrosis?
Caseating granulomas
Caseous necrosis
62
Granuloma with central necrosis
Caseating granuloma
63
Group of macrophages that form in response to infection, inflammation, foreign material
Granuloma
64
Which necrosis?
Caused by lipase breaking down fat cells, Ca2+ accumulates, seen in pancreatitis
Fat necrosis
65
Which necrosis?
Chalky, white deposits in fat
Fat necrosis
66
Which necrosis?
Outlines of dead fat cells, NO NUCLEUS
Fat necrosis
67
Which necrosis?
Caused by immune-mediated conditions, hypertension, occurs in vessels
Fibrinoid necrosis
68
Which necrosis?
Eosinophilic (pink) deposits in walls of blood vessels
Fibrinoid necrosis
69
Normal response to injury, cells travel where they're needed to kill infectious agents and clean damage
Inflammation
70
Name the cardinal signs
Heat (calor)
Redness (rubor)
Swelling (tumor)
Pain (dolor)
Loss of function (functio lasea)
71
Main cell type in acute inflammation
Neutrophils
72
How long does acute inflammation develop?
Mins/hrs
73
How long does acute inflammation last?
Hrs/days
74
Describe the tissue injury in acute inflammation
Mild and self-limited
75
Main cell types in chronic inflammation
Lymphocytes and macrophages
76
How long does chronic inflammation develop?
Days
77
Describe the tissue injury in chronic inflammation
Severe/progressive
78
What are the 4 causes of inflammation?
Infection (bacteria, fungus, parasite)
Necrosis
Foreign bodies (exogenous, endogenous)
Immune reactions (allergies, autoimmune diseases)
79
What are the 5 "Rs" of the inflammatory response?
Recognition of injurous agent
Recruitment of leukocytes
Removal of agent
Regulation of response
Resolution
80
What are the 3 key features of "Recognition of injurous agent"
Toll-like receptors
Inflammasomes
Circulating proteins
81
Receptors for microbes
Toll-like receptors
82
Where are Toll-like receptors found?
Plasma membranes for extracellular microbe detection
Endosomes for ingested microbe detection
83
What are Toll-like receptors expressed by?
Macrophages and dendritic cells
84
What do Toll-like receptors recognize in microbes?
PAMPs
85
What do Toll-like receptors produce to trigger immune response?
Cytokines
86
Sensors of cell damage and initiate inflammation
Inflammasomes
87
What do Inflammasomes recognize?
DAMPs
88
Name 3 examples of DAMPs
Uric acid (product of DNA breakdown)
ATP (released from damaged mitochondria)
DNA (shouldn't be in cytoplasm)
89
Inflammasomes activate a cascade resulting in ___________ production, which is what induces ______________
cytokine; inflammation
90
What do circulating proteins play a role in?
Complement system
91
Name the steps of "Recruitment of leukocytes"
Margination
Rolling/loose attachment
Adhesion
Transmigration
Chemotaxis
92
Cells go to periphery
Margination
93
Mediated by selectins; "speed bumps"
Rolling/loose attachment
94
Mediated by integrins
Adhesion
95
Travel between endothelial cells to exit
Transmigration
96
Chemical attractants direct to site of injury
Chemotaxis
97
Blood vessels maximize movement of plasma proteins and leukocytes out of circulation to site of injury by which 2 mechanisms?
Vasodilation
Increased vascular permeability
98
What occurs during "Removal of the agent"?
Phagocytosis
99
Consumption of pathogens or necrotic tissue
Phagocytosis
100
What happens to the agent during phagocytosis
Recognition by phagocyctic receptors
Engulfment
Destruction
101
What occurs during "Regulation of response"?
Response declines after inflammatory stimulus is gone
Anti-inflammatory lipoxins made
102
What is the half life of neutrophils in blood?
Hours to 2 days after leaving blood
103
What occurs during "Resolution"
Apoptosis of neutrophils
Disappear within 24 hours after resolution
104
What are the cell derived mediators of acute inflammation?
Arachidonic acid metabolites
Mast cell products
Cytokines
105
Produced from cell membrane phospholipids
Arachidonic acid metabolites
106
What are the key metabolites of Arachidonic acid metabolites?
Prostaglandins
Thromboxane A2
Leukotrienes
107
Promote vasodilation and vascular permeability; lead to redness/swelling
Prostaglandins
Histamine
108
Promotes platelet aggregation, vasoconstriction, clot formation
Thromboxane A2
109
Increase vascular permeability, act as chemotactic agents for leukocytes, contribute to bronchospasm
Leukotrienes
110
Role is to amplify and sustain inflammatory response
Arachidonic acid metabolites
111
What is the key product of mast cells?
Histamine
112
Role is to initiate and sustain inflammatory response, especially in allergic reactions
Mast cells
113
What is the key cytokine?
Interleukins
114
Promotes endothelial activation, fever, and activates leukocytes
Interleukins
115
Role is to regulate intensity and duration of inflammatory response
Cytokines
116
What is the plasma protein derived mediator of acute inflammation?
Complement system
117
Group of proteins that circulate blood in inactive form
Complement system
118
What are the key actions of the complement system?
Inflammation (release histamine)
Phagocytosis (coat pathogens)
Lysis of microbe (form MAC to puncture cell membranes for destruction)
119
Role is to bridge innate and adaptive immunity, enhancing ability to clear microbes and damaged cells
Complement system
120
What are the 3 activation pathways in the complement system?
Classical
Alternative
Lectin
121
Which activation pathways in the complement system?
ABs bind to pathogens
Classical
122
Which activation pathways in the complement system?
Activated directly by pathogen surfaces
Alternative
123
Which activation pathways in the complement system?
Mannose-binding lectin attaches to pathogen surface
Lectin
124
What are the 4 patterns of acute inflammation?
Serous
Purulent
Fibrinous
Ulcer
125
Exudation of cell-poor fluid into spaces; result from burn or viral infection
Serous
126
Produces pus, which is exudate of neutrophils, liquified debris of necrotic cells, and fluid (cell-rich); result from bacterial infection
Purulent
127
Localized collection of pus
Abscess
128
Fibrinous exudate; vascular leaks are large or a local procoagulant stimulus is present
Fibrinous
129
Local defect of surface epithelium produced by sloughing of inflamed necrotic tissue; common in oral cavity
Ulcer
130
What are the 3 possible outcomes of acute inflammation?
Complete resolution
Healing by CT replacement
Progression to chronic inflammation
131
Which outcome of acute inflammation?
Damaged parenchymal cells regenerate
Macrophages remove cellular debris and microbes
Edema resorbed by lymphatics
Complete resolution
132
Which outcome of acute inflammation?
Scarring or fibrosis
Substantial destruction, tissue can't regenerate, or abundant fibrin exudate can't be cleared
CT grows into area, creating mass of fibrous tissue
Healing by CT replacement
133
Which outcome of acute inflammation?
Injurous agent persists or something interferes with normal healing process
Progression to chronic inflammation
134
What type of inflammation?
Caused by persistent infections, hypersensitivity diseases, or prolonged exposure to toxins
Chronic inflammation
135
What are the 3 morphologic features of chronic inflammation?
Mononuclear cells (lymphocytes, macrophages, plasma cells)
Tissue destruction
Attempts at repair (angiogenesis, fibrosis)
136
Name the 4 main cell types involved in chronic inflammation
Macrophages
Lymphocytes
Plasma cells
Eosinophils
137
What cell?
Monocytes in blood, but become this cell in tissue
Macrophages
138
What cell?
Functions include phagocytosis, antigen presentation to T cells, cytokine production, tissue repair (secrete growth factors)
Macrophages
139
What cell?
Amplify and propagate chronic inflammation
Lymphocytes
140
What cell?
Include helper T cells (CD4), cytotoxic T cells (CD8), and B cells
Lymphocytes
141
What cell?
Release cytokines to activate other immune cells like macrophages
Helper T cells (CD4)
142
What cell?
Directly kill infected/damaged cells
Cytotoxic T cells (CD8)
143
What cell?
Differentiate into plasma cells
B cells
144
What cell?
Source is differentiated B cells
Plasma cells
145
What cell?
Functions include AB production and formation of immune complexes
Plasma cells
146
What cell?
Associated with allergic reactions and parasitic infections
Eosinophils
147
What cell?
Functions include release of cytotoxic granules, produce cytokines and chemokines, release mediators that contribute to tissue damage and remodeling
Eosinophils
148
Chronic inflammation that occurs when a material is difficult to digest or remove
Granulomatous inflammation
149
In what settings is granulomatous inflammation usually present?
Persistent T cell response to microbes
Immune-mediated inflammatory disease
Foreign body
150
Granulomas wall off the agent, but if the body can't remove it, what does this lead to?
Fibrosis
Organ dysfunction
151
Healing of granulomatous inflammation may cause what?
Extensive fibrosis
152
Describe the histopathology of granulomatous inflammation
Large epithelioid macrophages
Surrounding lymphocytes
Multinucleated giant cells
Central necrosis
153
What are the systemic effects of acute and chronic inflammation?
Fever
Lymphadenopathy
Leukocytosis
Acute-phase proteins
Increased HR/BP
Chills
Malaise
154
Caused by pyrogens (prostaglandins, cytokines)
Fever
155
Enlarged, tender lymph nodes due to immune cell proliferation
Lymphadenopathy
156
Increased circulating leukocytes; cytokines stimulate production from precursors in bone marrow
Leukocytosis
157
Made in liver, stimulated by cytokines, measured clinically to track progression of inflammation
Acute-phase proteins
158
Examples are C reactive protein, fibrinogen, serum amyloid A
Acute-phase proteins
159
What are the 2 main processes in repair?
Regeneration
Scar formation
160
Proliferation of cells that survived injury (or stem cells)
Regeneration
161
Deposition of CT, mostly collagen
Scar formation
162
What cells play a central role in repair?
Macrophages
163
What type of tissue ALWAYS results in scarring?
Permanent tissue (neurons, heart muscle, skeletal muscle)
164
Name the 3 cells/tissues that proliferate during regeneration?
Injured tissue (attempt to restore normal structure)
Vascular endothelial cells (nutrients for repair process)
Fibroblasts (fibrous tissue for scar)
165
Describe the repair sequence (days 1-14)
Clot forms immediately after injury
Day 1: Neutrophils phagocytose foreign substances/necrotic tissue
Day 2: Macrophages enter, granulation tissue forms, protected by fibrin clot
Day 3-6: Lymphocytes + plasma cells enter
Day 7: Clot digested, initial repair complete
Day 14: Fibroblasts mature, collagen remodeled forming scar tissue
166
When should you take sutures out?
Between 1 and 2 weeks
167
What scenarios will a scar form?
Permanent tissue
Extensive ECM damage
168
Excessive scar tissue often seen in chronic inflammation
Fibrosis
169
What is granulation tissue made of?
New blood vessels + immature fibroblasts
170
What is the formation of new blood vessels in granulation tissue mediated by?
VEGF
(vascular endothelial growth factor)
171
What is the migration and proliferation of fibroblasts in granulation tissue mediated by?
FGF
(fibroblast growth factor)
172
What is FGF (fibroblast growth factor) made by?
Macrophages
173
What does granulation tissue look like?
Red/pink and granular
174
How many days after injury does granulation tissue appear?
3-5 days after injury
175
Fibroblasts deposit ________, which is mediated by ________
collagen; TGF-beta
176
Stimulates production of and inhibits breakdown of ECM proteins; anti-inflammatory
TGF-beta
177
Migration and proliferation of fibroblasts and smooth muscle cells
PDGF
178
Stimulates collagen synthesis and fibroblast migration
IL-13 (cytokine)
179
What factors prevent healing and repair?
Infection
Nutrition
Steroid use
Poor perfusion
Foreign bodies
Type/extent/location of injury
Aberration of cell growth
180
Excessive formation of collagen during repair process
Keloid
181
What cell?
Released as inactive precursors, but activated by proteases at site of injury in remodeling process
Matrix metalloproteinases (MMPs)
182
What cell inhibits Matrix metalloproteinases (MMPs)?
Tissue inhibitors of metalloproteinases (TIMPs)
183
What do Matrix metalloproteinases (MMPs) degrade?
ECM proteins
184
What process are Matrix metalloproteinases (MMPs) involved in?
Remodeling
185
What are the 4 steps of hemostasis?
Arteriolar vasoconstriction
Primary hemostasis (platelet plug)
Secondary hemostasis (deposition of fibrin)
Clot stabilization & resorption
186
What occurs immediately after injury to reduce blood flow to the area?
Arteriolar vasoconstriction
187
What is arteriolar vasoconstriction mediated by?
Endothelin
188
Endothelium-derived vasoconstrictor
Endothelin
189
Which step of hemostasis is transient, meaning bleeding would resume if the next steps following it didn't occur?
Arteriolar vasoconstriction
190
What is exposed when endothelium is disrupted and promotes platelet adherence/activation?
vWF + collagen
191
Activated platelets change _______ to increase their __________ _________
shape; surface area
192
Which secretory granules do activated platelets release?
Adenosine diphosphate (ADP)
Thromboxane A2
193
How do platelets adhere to ECM?
Through binding of vWF + glycoprotein Ib
194
Activated platelets have high affinity for what?
Fibrinogen
195
What does fibrinogen bind to?
Glycoprotein IIb/IIIa
196
When platelets aggregate, what are they linked together by?
Fibrinogen
197
What is exposed at site of injury to activate secondary hemostasis?
Tissue factor
198
Membrane bound procoagulant glycoprotein
Tissue factor
199
What does tissue factor bind and activate?
Factor VII
200
Made by endothelial cells and limits clotting at site of injury
Tissue plasminogen activator (tPA)
201
What cells are the regulators of hemostasis?
Endothelial cells
202
Evaluates extrinsic pathway
Prothrombin Time
203
TF, phospholipids, and Ca2+ are added to plasma; time to form fibrin clot is recorded
Prothrombin Time
204
"Corrected Prothrombin Time," since results may vary depending on brand/manufacturer of reagents used
International Normalized Ratio
205
Evaluates intrinsic pathway
Partial Thromboplastin Time
206
Negatively charged particles (ground glass) are added; time to form fibrin clot is recorded
Partial Thromboplastin Time
207
Identifies problem with fibrinogen or thrombin inhibitor tissue
Thrombin Time
208
Amplifies coagulation cascade by activating factor XIII, but becomes anti-coagulant when in contact with normal endothelium to help control clotting
Thrombin
209
What 2 factors limit coagulation?
Dilution
Fibrinolytic cascade
