Pathology Flashcards
1
Q
Define Inflammation
A
The local physiological response to tissue injury
2
Q
Why does inflammation occur
A
To bring all essential cells for healing to the area of tissue damage
3
Q
Benefit of inflammation
A
destruction of invading microbes
4
Q
Harmful effects of inflammation
A
- Digestion of normal tissues
- Swelling
- Inappropriate inflammatory response
5
Q
2 main types of inflammation
A
Acute
Chronic
6
Q
Whats differs between acute inflammation and chronic
A
Duration, Cells involved, Cause
7
Q
What causes Acute Inflammation
A
- Tissue Necrosis
- Microbial Infections
- Hypersensitivity reactions (hay fever)
- Physical Agents (Radiation)
- Chemicals (acid)
8
Q
What causes Chronic Inflammation
A
- Transplant rejection
- Persistent infection (recurrent acute inflammation) or progression from acute inflammation (e.g. suppurative if an abscess is formed)
- Crohn’s disease/ulcerative colitis
- Autoimmunity
- Agent resistant to phagocytosis e.g.TB, leprosy
- Agent indigestible i.e. fat, bone, asbestos, silica
9
Q
Define autoimmunity
A
Immune responses of an organism against its own cells and tissues
10
Q
Define suppurative
A
Production or causing of pus
11
Q
*Give 5 cardinal signs of Acute Inflammation
A
- Swelling
- Redness
- Heat
- Pain
- Loss of function
12
Q
(cardinal signs of Acute Inflammation)
What causes Swelling?
A
Oedema - accumulation of of fluid in extravascular space (Interstitial fluid)
13
Q
(cardinal signs of Acute Inflammation)
What causes Redness?
A
Dilation of small blood vessels within the damaged area
14
Q
(cardinal signs of Acute Inflammation)
What causes Heat?
A
Due to Increased blood flow (HYPERAEMIA)
15
Q
(cardinal signs of Acute Inflammation)
What causes Pain?
A
Stretching and distribution of tissues to inflammatory oedema
16
Q
Define hyperaemia
A
increased blood flow
17
Q
Give 5 examples of inflammation
A
Acne Asthma Appendicitis Cellulitis Septic arthritis
18
Q
What are key cells involved in acute inflammation and what are their functions?
A
Neutrophil Polymorphs - Phagocytose pathogens
Macrophages - Secrete Chemical Mediators essential for Chemotaxis
19
Q
Describe Phagocytosis (of pathogens) and steps after
A
- Pathogens ingested by neutrophil polymorph (np) to form phagosome (phagocytic vacuole in np)
- Lysosomes fuse with phagocytic vacuole to form a phagolysosome
- Enzymes of lysosome(s) digest bacterium
- Bacterial debris released released from np and lysosomes replenished
20
Q
What is the role of chemical mediators in acute inflammation
A
spread the acute inflammatory response (following injury of a small area)
21
Q
Give 2 examples of chemical mediators and their functions
A
Histamine and Thrombin
both cause neutrophil adhesion to endothelial surface
thrombin also increases vessel permeability
22
Q
What produces histamine and thrombin
A
Histamine from Mast cells
Thrombin from Platelets
23
Q
What are the 3 main stages of acute inflammation?
A
-Changes in vessel calibre
-Fluid exudate
-Cellular exudate
(then chemotaxis)
24
Q
**Describe the main stages of acute inflammation
A
-Vasodilation brings blood and cells into the site of inflammation
-Vessels become more permeable by vasodilation and chemical mediators (e.g.histamine, bradykinin, NO).
This allows plasma proteins to leave vessels, which decreases oncotic pressure.
This causes fluid to leave vessels, forming fluid exudate.
-Accumulation of neutrophil polymorphs into the extracellular space and enzymatic cascades
-Chemotaxis
25
What is in exudate?
(protein-rich)
| contains antibodies and plasma proteins, such as fibrin and substances needed for inflammation
26
What are 4 enzymatic cascades (for accumulation of cellular exudate?
- Complement
- Coagulation
- Kinin
- Fibrinolytic
27
What is chemotaxis?
The attraction of cells to site (of inflammation) through release of chemicals.
Process by which neutrophils move to inflammation site, attracted to inflammatory mediators released.
28
Was are possible outcomes of acute inflammation?
Resolution - complete restoration of tissues to normal
Suppuration - formation of pus (also results in granulation tissue forming and scarring)
Organisation - when tissue is replaced with granulation tissue as part of healing process
Progression to chronic inflammation
29
Define suppuration
Formation of pus
30
Give examples of chronic inflammation
Ulcers, pulmonary fibrosis
31
Describe 3 general differences between acute and chronic inflammation
Chronic - long duration, slow onset, may not recover, fibrosis (scar tissue formation), less swelling than acute (less exudate formation)
Acute - short duration, rapid onset, often recover (also neutrophils more active here)
32
Give 2 examples of agent resistant to phagocytosis
TB
| Leprosy
33
Indigestible agents that can cause chronic inflammation
Fat, Bone, Asbestos, Silica
34
What cells are involved in chronic inflammation?
Macrophages; Plasma cells; B-lymphocytes; T-lymphocytes
35
Define fibrosis
scar tissue formation
| key feature of chronic inflammation
36
Why does acute inflammation have more swelling than chronic?
As more exudate is formed
37
What is the role of B-lymphocytes?
Differentiate into plasma cells to make antibodies
38
Role of T-lymphocytes?
Cell-mediated immunity
39
**Role of each immunoglobulin
IgG (gamma chains)- promote phagocytosis in plasma and activate complement system.
IgA (alpha chains)- initial defence in mucosa against pathogen agents
(found in mucosal secretions, tears, colostrum and milk)
IgM - first antibodies produced in large quantities against a pathogen. They promote phagocytosis and activate complement system.
(found on surface of B-cells so mainly in plasma)
IgE - important in allergic reactions
(IgD)
40
What is the only Ig that can cross the placenta?
IgG
41
Role of Plasma cells and where derived?
from B-lymphocytes
| produce antibodies
42
Role of macrophages
harbour organisms
eat up debris, present cells for antibody production
longer lived than neutrophils
43
Which macrophages encourage inflammation
M1 macrophages
44
Which macrophages decrease inflammation and encourage tissue repair
M2 macrophages
45
Granuloma define
Aggregate of epithelioid histiocytes
46
In a granuloma, what chemical do histiocytes excrete?
ACE
| blood marker if someone has systemic granulomatosis disease
47
4 examples of where granulomas can result
TB
Sarcoidosis
Leprosy
Crohn's
48
Define thrombus
Solid mass of blood constituents
49
What is meant by physiological thrombus
thrombus as a part of haemostasis (prevents bleeding outside vessels)
50
What is meant by pathological thrombus
where there is an imbalance in the blood coagulation system causing a thrombus
51
3 factors affecting the formation of a thrombus (Virchow's Triad)
Predisposing factors
Change in vessel wall (endothelial damage)
Change in blood flow (laminar to turbulent flow in arteries or stasis in veins)
Change in blood constituents (abnormal clotting factors, more platelets - hyper coagulability)
52
what type of inflammation and hypersensitivity is granuloma
Chronic
| Type IV hypersensitivity
53
what is primary cause of hypercoagulability
genetic
54
What are causes of abnormal blood flow?
Atherosclerosis; Aneurysm; Dilated atria; Atrial fibrillation; Venous stasis; Varicose veins
55
What are cause change in laminar flow of artery and vein resulting in thrombus?
Arteries - blood flow becomes turbulent
| Veins - stasis of blood (if not moving enough)
56
Causes of endothelial injury of heart vessels?
Myocardial infarction
| Valvulitis (cardiac chambers)
57
Causes of endothelial injury
Atherosclerosis; Vasculitis; Hypertension; Smoking
Artery specific - Chemical irritation
Veins- prolonged recumbency and inflammation
58
*Give 3 differences between an arterial and venous thrombosis
Arterial:
Mostly superimposed on an atheroma
High pressure
Made up mainly of Platelets (white thrombus)
Venous:
Most commonly due to stasis
Low pressure
Made up mainly of Coagulation factors (RBC, red thrombus)
59
What thrombosis is referred to as White thrombus and why
Arterial thrombosis as mainly made up of platelets
60
What thrombosis is referred to as Red thrombus and why
Venous thrombosis as mainly made up of coagulation factors or erythrocytes
61
What can arterial thrombosis lead to?
Myocardial Infarction
| Stroke
62
What can venous thrombosis lead to?
```
Deep vein thrombosis (DVT)
Pulmonary embolism (PE)
```
63
*How to treat Arterial thrombosis (give 2 examples)
Anti-PLATELETS
| e.g. Aspirin or Clopidogerel
64
*How to treat Venous Thrombosis (give 3 examples)
Anti-COAGULANTS
e.g. Warfarin, Heparin, NOACs (Rivaroxaban)
NOAC = novel oral anti-coagulant
65
What is the most important risk factor for atherosclerosis?
Hypercholestermia
66
What vessels does atherosclerosis affect?
Large and Medium
67
Name 3 modifiable and 3 non-modifiable risk factors for atherosclerosis
Modifiable - Smoking, hypertension, hyperlipidemia, diabetes
Non-modifiable - Age, Male sex, Post-menopausal, Family History
68
When is atherosclerosis life threatening?
When a thrombosis forms on a spontaneously disrupted plaque.
| Atherothrombosis
69
Define Atherosclerosis
A disease of the arteries characterized by the deposition of fatty material on their inner walls
OR
Focal elevated lesions formed in the intima
70
*Process of Atherosclerosis
- Endothelial cell dysfunction (lots of cholesterol damages wall)
- High levels of LDL in the blood will begin to accumulate in arterial wall
- Macrophages are attracted to site of damage and take up lipid to form foam cells (inflammatory response)
- Formation of fatty streak (earliest stage of plaque)
- Activated macrophages release lots of their own products e.g. cytokines and growth factors
- Smooth muscle proliferation (to intima) around the lipid core and formation of a fibrous cap (collagen)
71
How is thrombus caused?
If the unstable cap of the plaque ruptures and partially occludes the vessel.
Degeneration of the walls of arteries is caused by accumulated fatty deposits and scar tissue
72
Where are plaques more vulnerable?
areas of high stress as there's a thinner fibrous cap prone to rupture
73
**Define ischemia
inadequate blood supply to an organ or pat of the body (especially heart muscles)
OR
reduction in blood flow
74
**Define infarction
Ischemia (or reduction in blood flow) that leads to cell death due to lack of blood supply
75
Give complications of thrombus formation
Ischemia of tissue
Embolism (if thrombus is dislodged)
Aneurysm (plaques weaken wall of arteries)
76
Aneurysm of what artery can cause central abdominal pain especially in males >55
Abdominal Aortic Artery
77
Common places where a thrombus can result in ischemia
Popliteal artery
| Coronary artery
78
**Define Thrombosis (3 marks)
Solid mass of blood constituents
formed within intact vascular system
during life
79
**Define embolus (2 marks)
Mass of material in the vascular system
| Abel to become lodged within a vessel and block it
80
Why are the lungs, liver and some parts of brain at a lower risk of ischemia/infarction than other organs?
As they are all supplied by 2 blood vessels and don't have an End Artery Supply. Therefore if embolism or thrombosis occurs in one of vessels, there other is still able to supply it.
81
What 2 vessels supply the:
a) Liver
b) Lungs
c)Brain
a) Portal Vein
Hepatic Artery
b) Pulmonary arteries
Bronchial arteries
c) Circle of Willis (2 internal carotid arteries)
82
Define End Artery Supply
An artery that is the only supply of oxygenated blood to a portion of tissue.
Extra:
Do not anastomose with their neighbours.
No collateral circulation present.
83
What is most common cause of infarction?
Disruption in blood flow e.g. fibrous plaque
84
Other than thrombus dislodged, what can cause an embolism?
Air
Fat
Foreign Body (e.g. vegetations of bacteria)
85
What is pyrexia
fluctuating body temperature
86
Examples of anti-inflammatories
Ibuprofen
Steroids
NSAIDs
Analgesics
87
What can over-use of anti-inflammatories lead to?
Crohn's, Peptic Ulcer, Ulcerative Colitis, inflamed Fallopian tubes
88
Define Rheumatoid Arthritis
Inflammatory arthritis with granulomatous features
89
Systemic effects of Inflammation (6)
```
Pyrexia
Constitutional symptoms
Weight loss
Reactive hyperplasia of reticuloendothelial system
Haematological changes
Amyloidosis
```
90
What are outcomes of acute inflammation
Resolution
Suppuration
Organisation
Progression to chronic inflammation
91
What does the outcomes of acute inflammation depend on?
- Type of tissue involved
| - Amount of tissue destruction (this depends on the nature of the injurious agent)
92
Whats meant by resolution (from cell/tissue damage)?
Initiating factor removed
| Tissue undamaged or able to regenerate
93
Whats meant by repair (how is it different to resolution)?
Initiating factor still present
| Tissue damaged and unable to regenerate
94
What cells can regenerate? (6)
```
Hepatocytes (liver)
Pneumocytes (lungs)
All blood cells
Gut epithelium
Skin Epithelium
Osteocytes (Bone)
(PNS neurones)
```
95
What cells don't regenerate?
```
Myocardial cells (heart)
Neurones (CNS)
```
96
**Describe repair of tissue
Replacement on damaged tissue by fibrous tissue
| Collagen produced by fibroblasts
97
Examples of repair
Heart after myocardial infarction
Brain after Cerebral Infarction
Spinal Cord after trauma
98
In lobar pneumonia, on an X-ray, what do white parts show, what is mostly present in acute inflammation of alveoli, why can lung regenerate?
White parts are parts gone solid
Alveoli mostly filled with neutrophils
Pneumocytes can regenerate
99
If abrasion of skin is not properly sutured up, what can happen?
Gap can be filled with blood containing fibrin which weakly joins skin but fibroblasts eventually form collagen in gap (scar)
100
Describe what can happen after 2nd intention abrasion of skin
(alot of layers of skin removed in area)
| Fibroblasts and capillaries form granulation tissue, which can lead to scars (collagenous scar)
101
Describe 1st intention abrasion of skin
top layer of cells scrapped off and scab can form over surface
no scar as basal layer still remains and can regenerate
102
Risk factors of atherosclerosis
HBP (or hypertension sharing forces)
Smoking cigarettes
Hyperlipidemia (direct damage to endothelial cells)
Diabetes (superoxide)
103
Give two past/current theories of atherosclerosis occurance
Lipid Insulation Theory
| Endothelial Damage Theory (current)
104
What prevents stickiness of endothelial cells of BVs
Teflon coating of epithelial cells
| NO causes lack of stickiness
105
What 3 chemicals can damage epithelial teflon coating
Free Radicals
Nicotine
CO
106
*Define Apoptosis
Programmed cell death
that involves the controlled dismantling of intracellular components while avoiding inflammation and damage to surrounding cells
107
Give 2 examples of fully differentiated cells that apoptose?
Top of villi in gut
| Top of skin
108
What can trigger apoptosis
Cells no longer have potential to divide
| DNA damage
109
What protein detects DNA damage
p53
damage to p53 gene means DNA damage undetected so cell does not apoptose - can become cancerous
110
2 examples of apoptosis in disease
Cancer - lack of apoptosis as mutation in p53 gene
| HIV - too much apoptosis as virus binds to CD4 T-helper lymphocytes then can enter cells and cause apoptosis
111
*Define Necrosis
Traumatic cell death
112
Examples of necrosis
Frostbite; Cerebral infarction; Avascular necrosis of bone (scaphoid bone in hand; femural head if neck supply cut off); Pancreatitis
113
Types of necrosis
Coagulative - caused by ischemia or infarction
Liquefactive (or colliquative)
Caseous - tissue maintains cheese-like appearance
114
Describe liquefactive necrosis
Transformation of tissue into a liquid viscous mass (focal bacterial or fungal infections)
also symptom of internal chemical burn
115
What are role of caspases in apoptosis
Endoproteases (enzymes) that cause apoptosis by DNA fragmentation and membrane blebbing (via demolishing key structural proteins and activating other enzymes)
116
Describe extrinsic apoptotic signalling network
Fas (transmembrane receptor) and FasL (ligand/cytokine) are members of TNF family
- FasL binds to Fas, which brings together death domains (DD) on cytoplasmic tails.
- 'Fas-associated protein with death domain' (FADD) is an adaptor protein that binds activated DD to death effector domains (DED) that bind to pro-caspase 8.
- When pro-caspase 8s are brought together , they transactivate and cleave eachother to form Caspase 8, which leads to formation of Caspase 3.
- Caspase 3 cleaves ICAD to form CAD (caspase activated DNAase).
- CAD enters nucleus and cleaves DNA, resulting in apoptosis due to DNA damage.
117
What is TNF family
Tumour Necrosis Factor family
118
Describe the intrinsic apoptotic signalling network
- Cellular stress, such as growth factor withdrawal and p53 cell cycle arrest induces the expression of the pro-apoptotic Bcl-2 proteins (Bax and Bak).
- These form permissive pores on outer mitochondria causing release of Cytochrome C.
- Cytochrome C binds to Apaf1 to form an apoptosome.
- Apoptosome activates the initiator caspase, Caspase 9.
- Caspase 9 then activates effector caspase, Caspase 3.
- Caspase 3 cleaves ICAD to form CAD (caspase activated DNAase).
- CAD enters nucleus and cleaves DNA, resulting in apoptosis due to DNA damage.
Other molecules (anti-IAPs e.g. Smac, Omi) released from damaged mitochondria counteract the effect of IAPs (inhibitor of apoptosis proteins), which would normally bind and prevent the activation of pro-caspase 3.
119
What is effect of Anti apoptotic Bcl-2 protein on intrinsic apoptotic signalling network
Bcl2- when incorporated as a member of the Bax/Bak pore complex, renders the mitochondrial pore non-permissive to release of anti-IAPs and cytochrome C.
Prevents apoptosis.
120
Cytochrome C and Apaf1 bind to form what? (Intrinsic apoptosis)
Apoptosome
121
What is the effector caspase? (intrinsic apoptosis)
Caspase 3
122
Binding of FasL to Fas results in formation of which Pro-Caspase and caspase? (extrinisic)
Pro-caspase 8 -> Caspase 8 -> Caspase 3
123
What is initiator caspase? (intrinsic apoptosis)
Caspase 9
124
What can initiate intrinsic apoptosis pathway?
Cellular stress, such as growth factor withdrawal and p53 cell cycle arrest
that induces the expression of the pro-apoptotic Bcl-2 proteins (Bax and Bak), causing release of cytochrome C and anti-IAPs from mitochondria.
125
Give an example of apoptosis in development
Fingers are webbed in development and apoptosis helps separate the fingers
126
What is differences between congenital, inherited and acquired deficiencies
Congenital - present at birth (not necessarily genetic e.g. club foot)
Inherited - Caused by an inherited genetic abnormality (e.g. Huntingtons, Down's syndrome)
Acquired - caused by non-genetic environmental factors e.g. (Fetal alcohol syndrome)
127
What are homebox genes
A large family of similar genes that direct the formation of many body structures during early embryonic development
128
Examples of deficiencies due to problems during embryonic development
Spina Bifida (exposed spina cord)
also Meningocele, Myleomeningocele
Cleft palate
VSD (ventricular septal defect)
129
**Define Hypertrophy
Increase in size of a tissue caused by an increase in SIZE of the constituent cells
130
Define Hyperplasia
Increase in the size of a tissue caused by an increase in of NUMBER of constituent cells
131
Define Atrophy
Decrease in size of a tissue caused by a decrease in number of the constituent cells or a decrease in their size
132
Define Metaplasia
Change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type.
133
Define Dysplasia
Imprecise term for the morphological changes seen in cells in the progression to becoming cancer.
(change happen instead of metaplasia with severe/consistent damage or developmental abnormality)
134
Example of metaplasia
Bronchi: ciliated columnar epithelium to squamous epithelium (smoker)
(can no longer catch microbes -> cough)
135
Example of hypertrophy
Larger muscle but same number of myofibrils (so no change in strength, just look bigger) from steroids or condition
136
Examples of hyperplasia
Enlarged prostate
| Enlarged lining of womb (more oestrogen, less progesterone)
137
Conditions that can result from age
- Dermal elastosis (wrinkled skin)
- Cataracts
- Osteoporosis
- Alzheimers or Vascular dementia
- Sarcopenia
- Deafness
138
What causes dermal elastosis or cataracts
Increased (over time) exposure to UV-B light which causes protein cross-linking
139
What causes deafness?
Loss of hair cells in cochlea over time
140
What causes A or V dementia
Atrophy in the brain due to plaques of protein or neurofibrillary tangles or ishemia/infarction
141
What causes osteoporosis
Lack of oestrogen meaning decreased bone formation and increased resorption (post menopausal women)
142
What is meant by DIC?
Disseminated Intravenous Coagulation
| in gross infections or serious traumas
143
Which of these is an example of acute inflammation:
| Glandular fever, leprosy, TB, appendicitis
Appendictis
144
**Define granuloma
Macrophages surrounded by lymphocytes/neutrophils
145
What type of inflammation is lobar pneumonia
Acute
146
Give an example of Granulomatous inflammation
Crohn's disease
147
An enlarged left ventricle is an example what?
| Hyperplasia, hypertrophy, atrophy
Hypertrophy
148
Give an example of a condition you can be born with but not be genetic
Foetal Alcohol Syndrome
149
```
Which of the following has autosomal dominant inheritance?
FAP (Familial Adenomatous Polyposis)
Colour blindness
Cystic fibrosis
Sickle cell disease
```
FAP
150
Which of these is not an example of apoptosis:
Graft vs Host Disease
Renal Infarction
Renal Infarction
| cells die due to lack of blood, not due to apoptosis process
151
Which of these is an example of chronic inflammation from the start:
Cholecystitis
Infectious mononucleosis (aka Glandular fever)
Infectious Mononucleosis which starts as lymphocytes, not neutrophils
(Cholecystitis is acute at start)
152
*Which of these is NOT associated with dementia?
Huntingtons disease
Downs syndrome
Cerebral palsy
Cerebral Palsy
153
Give an example of hyperplasia
Benign prostate enlargement
154
Which of these cells CAN regenerate
Hepatocytes
Myocytes
Nephrons
Hepatocytes
(Myocytes=heart, cant regenerate)
(Nephrons=kidney ")
155
Give 4 examples of DNA damage
Single-strand break
Double-strand break
Base alteration
Cross-linkage
156
What protein detects DNA damage?
p53
| Apoptosis triggered if DNA damage
157
Describe how granulomatous tissue can develop from
Occurs when the immune system attempts to wall off substance but is unable to eliminate it.
This forms a granuloma (a collection of epithelioid histiocytes (macrophages))
158
Most is the most common form of acute to chronic progression of inflammation
Suppurative type
159
Describe suppurative type of progression from acute to chronic inflammation
Pus forms in deep-seated abscess cavity.
Drainage is delayed or inadequate and so by the time drainage occurs, the abscess will have developed thick walls composed of granulation and fibrous tissues.
Rigid walls of abscess cavity will thus fail to come together after eventual drainage and the stagnating pus within the cavity becomes organised by the ingrowth of granulation tissue, eventually to be replaced by fibrous scar.
160
Example of chronic abscess
Osteomyelitis
| Abscess in the bone, which is difficult to eradicate due to poor access by macrophages
161
The presence of indigestible material can cause progression to chronic inflammation - give examples
Keratin (from ruptured epidermal cyst)
Fragments of necrotic bone
(both are relatively inert and resistant to lysosomal enzyme action)
Foreign body materials such as surgical suture, wood, metal or glass (chronic suppuration)
162
What type of inflammation can result from foreign bodies?
Granulomatous Inflammation
| Cause macrophages to form multinucleate giant cells called 'foreign body giant cells'
163
Example of recurrent acute inflammation resulting in chronic inflammation
Recurring gallstones
| Result in Chronic Cholecystitis
164
Commonest form of granuloma
Tuberculosis
165
Macroscopic appearances of chronic inflammation
```
Chronic ulcer
Chronic abscess cavity
Thickening of the wall of a hollow organ
Granulomatous inflammation
Fibrosis
```
166
What is fibrosis and when is it most prominent
Macroscopic appearance of chronic inflammation
Thickening or scarring of connective tissue
Becomes most prominent when most of the chronic inflammatory cell infiltrate has subsided
167
Causes of primary chronic inflammation (no acute phase)
Resistance of infective agent to phagocytosis and intracellular killing e.g. TB, leprosy
Endogenous materials e.g. necrotic adipose tissue, bone, uric acid crystals
Exogenous materials e.g. silica, asbestos materials, suture materials
Some autoimmune diseases
Specific disease of unknown aetiology e.g. IBD (UC)
Primary granulomatous diseases e.g. Crohns, sarcoidosis
168
Autoimmune diseases that can cause primary chronic inflammation
Organ-specific e.g. Hashimotos thyroiditis, Chronic gastritis of pernicious anaemia
Non-organ-specific e.g. Rheumatoid arthritis
Contact hypersensitivity reactions e.g. self-antigens altered by nickel
169
What does cellular infiltrate mainly consist of in chronic inflammation
Lymphocytes
Plasma cells
Macrophages
170
Describe healing in chronic inflammation:
| Paracrine stimulation of connective tissue proliferation
- Involves the regeneration and migration of specialised cells
- The predominant features in repair are angiogenesis (formation of new blood vessels) followed by fibroblast proliferation and collagen synthesis resulting in granulation tissue
- These process are regulated by proteins called growth factors which bind to specific receptors on cell membranes and trigger a series of events culminating in cell proliferation
171
**Examples of Growth factors involved in healing and repair associated with inflammation. State their specific functions also
Epidermal Growth Factor (EGF)
Transforming growth factor-alpha (TGF-a)
(both regeneration of epithelial cells)
TGF-beta (stimulates fibroblast proliferation and collagen synthesis; controls epithelial regeneration)
Platelet-derived growth factor (PDGF) - mitogenic and chemotactic for fibroblasts and smooth muscle cells
Fibroblast growth factor (FGF) - stimulates fibroblast proliferation, angiogenesis and epithelial cell regeneration
Insulin-like growth factor-1 (IGF-1) - synergistic effect with other growth factors
Tumour necrosis factor (TNF) - stimulates angiogenesis
172
Which growth factors stimulate angiogenesis
TNF (Tumour necrosis factor)
| FGF (Fibroblast Growth Factor)
173
Which growth factors stimulate regeneration of epithelial cells
EGF Epidermal Growth Factor
TGF-alpha (transforming growth factor-a)
TGF-beta
174
Which growth factors stimulate fibroblast proliferation
FGF fibroblast growth factor
| TGF-beta
175
Function of Platelet derived growth factor (PDGF)
Mitogenic and chemotactic for fibroblasts and smooth muscle cells
176
Function of IGF-1
Synergistic effect with other growth factors
177
How do macrophages moves through tissues
Amoeboid motion
178
Important cytokines produced by macrophages
Interferon-alpha and -beta
Interleukin-1, -6 and -8
Tumour necrosis factor- alpha
179
Role of macrophages in inflammation
Can ingest a wider range of materials then neutrophil polymorphs can
and, being long-lived, they can harbour viable organisms if they are unable to kill them by their lysosomal enzymes
180
Example of an organism that can survive within macrophages
Mycobacteria:
Mycobacterium tuberculosis
Mycobacterium Leprae
181
Causes of granulomas
Specific infections e.g. Mycobacteria (TB, leprosy), Types of fungi, Parasites, Larvae, Eggs and Worms, Syphilis
Materials that resist digestion (endogenous and exogenous)
Specific chemicals e.g. Beryilium
Drugs (Hepatic granulomas from Allopurinol, Phenylbutazone, Sulphonamides)
Others e.g. Crohn's disease, Sarcoidosis, Wegeners granulomatosis
182
Examples of endogenous materials that resist digestion
Keratin
Necrotic bone
Cholestrol crystals
Sodium urate
183
Examples of exogenous materials that resist digestion
```
Talc
Silica
Suture materials
Oils
Silicone
```
184
What are histiocytic giant cells and when can they appear
Form when 2 or more macrophages attempt simultaneously to engulf the same particle - their cell membranes fuse and the cells unite. Resulting multinucleate giant cells with >100 nuclei have little phagocytic activity and no known function.
Form when foreign particles are too large to be ingested by a single macrophage or where particulate matter, that is indigestible by macrophages, accumulates e.g. inert materials such as silica or bacteria like tubercle bacilli
185
Examples of histiocytic giant cells
Langerhans giant cells (characteristically seen in Tuberculosis)
Foreign body giant cells (seen in relation to particulate foreign body material)
Touton giant cells (seen when macrophages attempt to ingest lipids or in relation to xanthomas/dermatofibromas on skin)
186
Role of acute inflammation in systemic conditions
CVS system in response to acute MI and the generation of some complication of MI such as cardiac rupture
187
Role of chronic inflammation in systemic conditions
Initiation and propagation of cancer and in its progression e.g. in Ulcerative colitis
Involved in myocardial fibrosis after MI
188
Roles of inflammation in general in systemic and organ-specific diseases
Atheroma development
| Tissue injury and neurodegenerative disorder of CNS - multiple sclerosis
189
Role of inflammation in atheroma development
Macrophages adhere to endothelium, migrate into the arterial intima and, with T lymphocytes, express cell adhesion molecules which recruit other cells into the area
The macrophages are involved in processing the lipids that accumulate in atheromatous plaques
(Form foam cells)
190
Define chronic inflammation
The subsequent and often prolonged tissue reactions to injury following the initial response.
Can also be defined as an inflammatory process in which lymphocytes, plasma cells and macrophages predominate.
191
Causes of chronic inflammation
Primary chronic inflammation
Transplant rejection
Progression from acute inflammation
Recurrent episodes of acute inflammation
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Macroscopic appearances of chronic inflammation
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Chronic ulcer
Chronic abscess cavity
Thickening of wall of a hollow organ
Granulomatous inflammation
Fibrosis
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Microscopic features of chronic inflammation
Cellular infiltrate consists characteristically of lymphocytes, plasma cells and macrophages
Some eosinophils may be present but neutrophil polymorphs are rare
Some macrophages may form multinucleate giant cells
Exudation of fluid not prominent
May be continuing destruction of tissue at same time as repair and regeneration
Necrosis can be present (granulomatous disease)
194
2 lymphocytes in lymphocytic infiltrate in chronic inflammation
B-lymphocytes (contact with antigen, progressively transform into plasma cells that secrete antibodies)
T-lymphocytes = responsible for cell-mediated immunity; on antigen contact, produce range of soluble factors called cytokines (recruitment and activation of other cells like macrophages)
195
What stain can identify tuberculosis
Ziehl-Neelsen stain
| bright red
196
What is a likely cause of granulomas with many eosinophils
Parasitic infection such as worms
197
Locations in body of stem cells
Skin Epidermis in basal layer (immediately adjacent to BM), hair follicles and sebaceous glands
Intestinal mucosa near bottom of crypts
Liver between hepatocytes and bile ducts
Haemopoietic stem cells in bone marrow
198
When can complete restoration occur
Loss of part of a labile cell population can be completely restored
199
Healing of minor skin abrasion
* The epidermis is lost over a limited area, but at the margins of the lesion there remain cells that can multiply to cover the defect
* At first, cells proliferate and spread out as a thin sheet until the defect is covered
* When a confluent layer has been formed, the stimulus to proliferate is switched off; this is known as contact inhibition, and controls both growth and movement
* Once in place, the epidermis is rebuilt from the base up until it is indistinguishable from normal - this whole process is called healing
200
What is organisation
The repair of specialised tissues by the formation of a fibrous scar
201
**Formation of granulation tissue
Specialised or complex tissue is destroyed and cannot be reconstructed
Capillary endothelial cells proliferate and grow into the area to be repaired and can grow into vascular channels - these vessels are arranged as a series of loops arching into the damaged area
At the same time, fibroblasts are stimulated to divide and to secrete collagen and other matrix components. They also acquire bundles of muscle filaments and attachments to adjacent cells - these modified cells are called myofibroblasts (secrete collagen and important for contraction)
Combination of capillary loops and myofibroblasts is known as GRANULATION TISSUE
202
What cells secrete collagen (in granulation tissue)
Myofibroblasts
203
Describe wound contraction and scarring formation (also why is wound contraction important)
Wound contraction results from the contraction of myofibroblasts in the granulation tissue - these are attached to each other and to the adjacent matrix components, so that granulation tissue as a whole contracts and indrawn the surrounding tissues. This reduces the volume of tissue for repair and thus reduces tissue defect.
Collagen is secreted and forms a scar (replacing lost specialised tissue).
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Issues with wound contraction
- If the tissue damage is circumferential around the lumen of a tube (e.g. gut), subsequent contraction may cause stenosis (narrowing) or obstruction
- Similar tissue distortion can result in permanent shortening of a muscle (called a contracture)
- Burns to the skin can be followed by considerable contraction, with resulting cosmetic damage and often impaired mobility
205
Healing incised wound of skin - healing by first intention
Incision that causes little damage to tissue on either side of cut.
-Some small blood vessels will have been cut but these will be occluded by thrombosis.
-Fibrin deposited locally will bind the two sides of the wound.
-Coagulated blood on the surface of the wound will form a scab and helps to keep the wound clean (this join is very weak but is formed rapidly and is a framework for the next stage). (It is important that this framework is not disrupted thus why sutures, sticking plasters and other means of mechanical support are extremely useful.)
-Over the next few days, capillaries proliferate sufficiently to bridge the tiny gap, and fibroblasts secrete collagen as they migrate into the fibrin network.
If the sides of the wound are very close then such migration is minimal as would the amount of collagen and vascular proliferation required.
-By about 10 days the strength of the repair is sufficient to remove any plasters etc - the only residual defect will be the failure to reconstruct the elastic network in the dermis.
206
Healing by second intention e.g. in tissue loss etc
Wound margins are not apposed
Local haemorrhage will keep the sides apart and prevent healing by first intention, infection similarly compromises healing
Involves:
- Phagocytosis to remove any debris
- Granulation tissue to fill in defects and repair specialised tissue lost
- Epithelial regeneration to cover the surface
Time scale depends on size of defect as determines amount of granulation tissue
Final result depends on amount of tissue loss and thus scarring amount
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Healing of liver architecture
When can liver heal and when can it not
What can result from damage
Hepatocytes are stable cell population and have good regenerative capacity.
Sometime hepatic regeneration from Liver Progenitor cells (not hepatocytes).
Liver structure cant be reconstructed if severely damaged. But condition only causing hepatocyte loss may still completely resolve, but destruction of both may not.
Imbalance between hepatocyte regeneration and failure to reconstruct the architecture may proceed to cirrhosis. However, following the partial surgical resection of the liver there can be substantial regeneration of functioning liver.
208
Different things that can be an embolus
Solid or Gas
| Eg. Cholestrol crystals from plaque, tumour amniotic fluid, fat
