Cellular response to injury; recovery from injury Flashcards
(149 cards)
1
Q
One or more cell types that are functionally connected
A
Tissue
2
Q
List the three factors associated with tissue growth/proliferation (three different things that INCREASE)
A
- Increase in cell number by mitosis (multiplication)
- Increase in cell size
- Increase in extracellular tissue
3
Q
What types of tissue are highly proliferative in adults? (3)
A
Skin cells, epithelium of gut and respiratory tract, blood cells
4
Q
The acquisition of specialised function and related morphology of cells or tissue
A
Differentiation
5
Q
List three qualities of cells that are able to proliferate
A
- Labile
- Stable
- Permanent
6
Q
This describes cells that continuously proliferate, have a short life span and rapid turnover (e.g. blood cells, epithelial cells like oral mucosa)
A
Labile
7
Q
This describes cells that have a good regenerative ability, but would normally have a low cell turnover (e.g. hepatocytes after liver resection)
A
Stable
8
Q
These cells have either limited or no regenerative ability (e.g. cardiomyocytes, neurons)
A
Permanent
9
Q
The increase in cell size resulting from an increase in structural components. Leads to increase in tissue/organ size and function
A
Hypertrophy
10
Q
What is the only adaptive response seen in permanent cells?
A
Hypertrophy
11
Q
Name an example of physiological hypertrophy
A
Weight training resulting in skeletal muscle hypertrophy, or increase in size of pregnant uterus
12
Q
Name an example of pathological hypertrophy
A
Left ventricular hypertrophy or BPH
13
Q
An increase in cell NUMBER is known as
A
Hyperplasia
14
Q
Name an example of physiological hyperplasia
A
Change in breast tissue due to lactation, or regrowth of hepatocytes after liver resection
15
Q
Name an example of pathological hyperplasia
A
Gynecomastia in men, endometrial hyperplasia, or prostatic hyperplasia
16
Q
Pathological hyperplasia is often the result of excess _________ stimulation
A
hormonal
17
Q
True or false: adaptive changes are reversible
A
True
18
Q
The reduction in the cell size and number. Related to decrease of function in the tissue or organ. Often hormonally regulated.
A
Atrophy
19
Q
Reduced hormonal stimulation of tescticular, ovarian, breast, or endomentrial tissues results in
A
physiological atrophy
20
Q
List some examples of pathological atrophy
A
- Denervation of muscle due to trauma or neurological disorders
- Muscle atrophy in immobilisation
- Vascular atrophy of the brain in ageing
- Atrophy that results from malnutrition/starvation
21
Q
Reversible change where one differentiated cell type or tissue is replaced by another differentiated cell (often seen in epithelium)
A
Metaplasia
22
Q
The type of change that takes place when the epithelium in the squamo-columnar junction changes from simple columnar to stratified squamous in response to declining estrogen levels
A
physiological metaplasia
23
Q
List examples of pathological metaplasia
A
- Bronchial metaplasia in response to smoking (ciliated columnar –> stratified squamous epithelium)
- Barrett’s oesophagus (stratified squamous epithelium –> columnar epithelium incl intestinal goblet cells)
24
Q
Cellular injury occurs when _________ is no longer possible
A
adaptation
25
In which type of cell death does the cell membrane rupture?
Necrosis
26
In which type of cell death does the nuclei fragment?
Apoptosis
27
In which type of cell death does the nuclei shrink?
Necrosis
28
In which type of cell death do the cell contents leak?
Necrosis
29
Which type of cell death causes an inflammatory response?
Necrosis
30
Which type of cell death is always pathological?
Necrosis
31
In which type of cell death does the cell membrane remain intact, but altered?
Apoptosis
32
The pathway of programmed cell death is also called
apoptosis
33
Which type of cell death utilises the activation of intracellular enzymes to degrade DNA & proteins?
Apoptosis
34
Which type of cell death is associated wtih ATP depletion, influx of calcium ions, mitochondrial damage, and an increase in oxygen radicals?
Necrosis
35
Name the three different patters of necrosis
1. Coagulative (kidney wedge)
2. Liquefactive (brain in strokes)
3. Caseating (TB)
36
The death-receptor mediated pathway to apoptosis is also known as the
extrinsic pathway of initiation
37
The mitochondrial mediated pathway to apoptosis is also known as the
instrinsic pathway of initiation
38
Name the four phases of apoptosis
1. Induction
2. Effector
3. Degradation
4. Phagocytosis
39
Examples of this type of apoptosis include embryogenesis, involution of hormone dependent tissues after hormone withdrawl, and destruction of inflammatory cells
Physiologic apoptosis
40
DNA damage or accumulation of abnormal proteins may result in what type of cell death?
Pathological apoptosis
41
A type of cell death that may be associated with neoplasia is
autophagy-associated cell death
42
When the cell breaks down its own contents as a survival mechanism in nutrient deprivation, this is known as
autophagy-associated cell death
43
What are the typical symptoms of injury/inflammation? (4)
Redness, swelling, heat, and pain
44
What the Latin terms for the clinical signs of injury/inflammation?
Rubor, Tumor, Calor, Dolor, and Functio laesa
45
The local response of living tissue to injury from any agent which could be microbial, immunological, physical, or chemical.
Inflammation
46
Bacteria at the site of the wound relase _________ that reach the bloodstream, which send a message to the brain to produce a _________.
cytokines, fever
47
A clinical condition characterised by widespread activation of the inflammatory system, secondary to infection or significant trauma
Systemic inflammation
48
What are the three major phases of the acute inflammatory response?
1. The vascular phase
2. Neutrophil phase
3. Macrophage phase
49
Describe what happens in the vascular phase of acute inflammation
1. Increased blood flow
2. Dilation of small blood vessels
3. Increased movement of fluid from blood to tissue producing swelling/edema
50
Describe what happens in the neutrophils phase of acute inflammation
This is the initial appearance of neutrophils, the first type of leucocyte at the site of injury, which predominate in the inflammatory infiltrate during the first 6 - 24 hours after injury.
51
Describe what happens in the macrophage phase of acute inflammation
This is the later appearance of macrophages, the second type of leukocyte to arrive at the site of injury, generally after 24-48 hours.
52
What causes the swelling and oedema in the vascular phase of acute inflammation?
Short answer:
Increased movement of fluid from blood vessels to the tissues.
Long answer:
1. Endothelial cells at the site of injury initially swell, then contract to increase the space between them, thereby increasing the permeabillity of the vascular barrier.
2. Exudation of fluid leads to a net loss of fluid from the vascular space into the interstitial space, resulting in oedema.
53
What is the predominant cell of acute inflammation?
Neutrophil
54
What attracts neutrophils to the site of injury?
Chemotaxins
55
List the four stages of neutrophil migration
1. Margination
2. Rolling
3. Adhesion
4. Emigration
56
This stage of neutrophil migration is where WBC's line up against the endothelium
Margination
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This stage of neutrophil migration is where receptor ligands, called selectins, help the neutrophil loosely adhere to the endothelium. The neutrophils can then roll along the endothelium.
Rolling
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This stage of neutrophil migration is where neutrophils firmly attach to the endothelium via integrins. These help the next process of attachment.
Adhesion
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This stage of neutrophil migration is where cells move through the vessel wall to the affected area. The Ig family molecules invloved in transmigration are ICAM-1, VCAM-1, and PECAM-1.
Emigration
60
What happens immediately after extravasation in the acute phase of injury? (hint: where do the WBC's have to get to?)
Leucocytes emigrate in tissues toward the site of injury by chemotaxis (along a chemical gradient).
61
Examples of ____________ include complement protein C5a, leukotriene, and certain chemokines like MCP.
chemoattractants
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The process by which specialised cells engulf or ingest other cells or particles
Phagocytosis
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Phagocytosis involves the following three steps:
1. Recognition and attachment
2. Engulfment with subsequent formation of a phagocytic vacuole
3. Killing or degredation of the ingested material
64
The process of coating a pathogen to target it for phagocytosis is called
Opsonisation
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What is the role of opsonins?
They coat pathogens to target them for phagocytosis
66
Name two types of opsonins
1. Antibodies such as IgG
| 2. Compenents of the complement system such as C3
67
Opsonins such as antibodies or C3 (of the complement system) are recognised by __________.
Phagocytes
68
Describe the role of "scavengers"
Leukocytes (neutrophils and macrophages) ingest offending agents and get rid of necrotic tissue and foreign substances.
69
What type of cell is the first line of defense in the innate arm of the immune system?
Neutrophils
70
Where are neutrophils stored and released from?
The bone marrow
71
Are neutrophils granulocytes or agranulocytes?
Granulocytes
72
Which type of phagocyte is most abundant in the circulation?
Neutrophils
73
Macrophages are derived from
monocytes
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Which type of phagocyte has a multi-lobed nucleate?
Neutrophil
75
Are macrophages granular or agranular?
Agranular
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What phagocyte is considered second line in microbe destruction?
Macrophage
77
What types of cells do neutrophils mainly send signals to?
Other neutrophils and also macrophages
78
Do macrophages belong to the innate or adaptive arm of the immune system?
Adaptive
79
What type of cell is the most important modulator of both inflammation and immune responses?
Neutrophil
80
What is the mechanism that some neutrophils use to trap microbes that can't be phagocytosed or attacked with granules?
NETosis, or extracellular traps
81
What is the "parent cell" of a neutrophil?
Myeloblast
82
Agranulocytes develop from
lymphoblasts and monoblasts
83
Which leukocytes are considered granulocytes?
Neutrophils, basophils, eosinophils
84
Which type of cell is most proficient at clearing away debris, dead neutrophils, and dead microbes?
Macrophages
85
What types of cells do macrophages signal?
Other cell types to start healing, and antigen presenting cells
86
What type of cell produces growth factors for the proliferation of various cells in the healing response?
Macrophages
87
Monocytes circulate in the ________, and then migrate to the tissues to become __________.
blood, macrophages
88
Collagenase and elastase are involved in removal of
injured tissue and debris
89
Nitric acid and ROS are growth factors that have ___________ activity
antimicrobial
90
PDGF, TGF beta, TNF, IL-1, and KGF-7 are growth factors involved in _____________ and the proliferation of fibroblasts and keratinocytes
chemotaxis
91
Name the growth factors associated with angiogenesis
VEGF, FGF2, and PDGF
92
TGF beta, PDGF, TNF, OPN, IL-1, and collagenase are growth factors involved in the deposition and remodelling of the ____________________
extra cellular matrix
93
What are the two types/categories of mechanisms for intracellular killing?
Oxygen dependent and non-oxygen dependent
94
What is the oxygen-dependent mechanism of intracellular killing by neutrophils?
Myeloperoxidase
95
What is the oxygen-dependent mechanism of intracellular killing by macrophages?
Peroxynitirite
96
What types of oxygen-independent mechanisms do neutrophils and macrophages use for intracellular killing?
Granules containing multiple bactericidal proteins (neutrophils), and lysosomes containing enzymes
97
Membrane-bound organelles filled with hydrolytic enzymes
Lysosomes
98
List the three basic steps of how the body recovers from injury (the "3 R's"):
1. Resolution and scavenging
2. Regeneration
3. Repair
99
The proliferation of cells and tissues of the same type to replace lost structures
Regeneration
100
Continuously diving cells are known as
Labile
101
Name a few examples of labile cells
skin, mucosa of GI, and blood cells
102
Another word for cells that are stable is
quiescent
103
Name a few examples of cells that are stable
Liver, kidney, endothelium
104
Name some examples of tissues that are permanent
Heart, brain
105
The ability of tissue to regenerate is dependent on what two factors?
1. The extent of the damage (regeneration is possible with limited damage)
2. The integrity/preservation of the ECM (scaffolding) or the basement membrane
106
What results from either extensive tissue damage or disruption of the basement membrane?
Scarring
107
Cell proliferation is dependent on production of polypeptides known as _________ factors and __________ factors acting on signalling pathways to unlock cell cycle controls.
growth, transcription
108
Name some of the growth factors involved in regeeration of tissue
```
Transforming growth factor
Epidermal growth factor
Vascular endothelial growth factor
Fibroblast growth factor
Platelet-derived growth factor
```
109
What signals stem cells and local adjacent cells (near the damaged tissue) to proliferate?
Growth factors and transcription factors acting on signalling pathways, which unlocks cell cycle controls.
110
These cells are characterised by the self-renewal properties and by their capcity to generate differentiated cell lineages
Stem cells
111
Name some areas where stem cells "pool" in different tissues
1. Crytps of the colonic epithelium
2. Bone marrow
3. Hair follicles
112
This process is comprised of four parts:
1. Clearance of injurious stimuli
2. Clearance of mediators and acute inflammatory cells
3. Replacement of injured cells
4. Return to normal function
Resolution
113
When tissue damage is too extensive for regeneration or resolution, this type of cell patches the damage through fibrosis:
Fibroblasts
114
Scars are formed by the deposition of ___________ and other ECM componenents.
Collagen
115
List the 5 steps of the repair process
1. Angiogenesis
2. Granulation tissue
3. Fibrosis - scar formation
4. Scar remodelling
5. The final scar
116
Name the two of the signalling molecules involved in angiogenesis
Histamine and NO
117
Angiogenesis is mainly controlled by which growth factor?
Vascular endothelial growth factor
118
What is granulation tissue composed of?
New blood vessels, fibroblasts, and the remaining inflammatory cells
119
What is the result of newly formed blood vessels being leaky?
Oedema
120
What type of cell produces growth factors associated with scar formation/fibrosis?
Macrophages
121
Growth factors from macrophages leads to the migration and proliferation of ____________ into the granulation tissue.
Fibroblasts
122
What type of cell produces collagen and ECM?
Fibroblasts
123
Fibroblasts, and ultimately the process of fibrosis, is mainly controlled by which growth factor?
Transforming growth factor beta
124
In scar remodelling, collagen changes into type ____ collagen
one
125
Interactions of collagen deposition and degredation by matrix metalloproteinases (MMP's) are associated with which phase of the repair process?
4. Scar remodelling
126
In scar remodelling, what causes contraction of the scar tissue?
myofibroblasts
127
The final scar has a maximum of _____% of normal skin strength.
80
128
Name some local factors which frustrate would healing
```
Local infection
Foreign body
Haematoma
Denervation
Poor blood supply
Mechanical stress
Necrotic tissue
Site (lip vs foot)
Cause of insult is important (burns vs cuts)
```
129
Name some systemic factors which frustrate wound healing
```
Age
Anaemia
Drugs
Diabetes
Genetic disorders
Malignancy
Malnutrition
Obesity
Vitamin C deficiency
Trauma, shock
Systemic infection/sepsis
```
130
Describe the vascular phase of the "wound healing timeline"
1. Within minutes, vasoconstriction of damaged vessels leads to coagulation and stasis
2. Then vasodilation leads to increased hydrostatic pressure, resulting in oedema
131
When does granulation tissue begin forming in wounded tissue?
About 12-24 hours after injury
132
How soon after injury does epithelialisation and reformation of the basement membrane occur?
About 6-12 hours after injury
133
Tissue repair and regeneration depend on components of the _________
Extra cellular matrix
134
What four things is ECM composed of?
1. Fibrous structural proteins
2. Adhesive glycoproteins
3. Proteoglycans
4. Hyaluronan
135
The substances that provide ECM with resilence and lubrication are:
Proteoglycans and hyaluronan
136
What connects matrix elements to one another and to cells (within the ECM?)
adhesive glycoproteins
137
What are the fibrous structural proteins within ECM?
Collagen and elastins
138
Name a few of the "resident cells" of the ECM
1. Fibroblasts
2. Macrophages
3. Adipocytes
4. Mesenchymal cell
139
Protein fibres are composed of:
1. Elastic fibres
2. Collagen fibres
3. Reticular fibres
140
What is chronic inflammation?
Inflammation of prolonged duration- weeks or months
141
What are the two main types of celss involved in chronic inflammation?
Lymphocytes and macrophages
142
These are the three histological features of chronic inflammation:
1. Collection of chronic _______________ cells
2. Destruction of ______________
3. Replacement by ___________ tissue
1. inflammatory
2. parenchyma
3. connective
143
A distinctive pattern of chronic inflammation that is encountered in a limited number of infections, where the body produces a cellular attempt to contain an offending agent that is difficult to eradicate
Granulomatous inflammation
144
Name the four different types of granulomatous inflammation
1. Necrotising
2. Non-necrotising
3. Caseating (think TB)
4. Foreign body
145
What is the main cell type in a granuloma?
Macrophage
146
If the body cannot resolve the local inflammation, a whole-body response is initiated in an attempt to combat the insult. This is known as:
sepsis
147
List four potential negative outcomes of sepsis
1. Organ hypofunction
2. Multiple organ dysfunction syndrome
3. ARDS
4. Death
148
The cytokines that activate the immune response in systemic inflammatory response syndrome (SIRS), leading to the release of high amounts of inflammatory cells from the bone marrow are called
TNF and IL-1
149
What stimulates leukocytes to release cytokines such as TNF and IL-1?
Bacterial products such as pyrogens
