Pathology 2 Flashcards
1
Q
Define Acute Inflammation
A
Initial, transient series of tissue reactions to injury
Lasts hours to days
2
Q
Example of acute inflammation
A
Appendicitis
3
Q
State 2 benefits of inflammation
A
Destroys invading microorganisms
Walls off abscess cavity ∴ prevents spread of infection
4
Q
State 2 disadvantages of inflammation
A
Fibrosis can distort tissue and alter function
Abscess (e.g. in brain) can act as space-occupying lesion ∴ compressing surrounding structures
5
Q
List some examples of acute inflammation
A
Microbial infections (e.g. bacteria, viruses)
Hypersensitivity reactions (e.g. parasites)
Physical agents (e.g. trauma)
Chemicals (e.g. corrosives)
Bacterial toxins
Tissue necrosis (e.g. ischaemic infarction)
6
Q
Describe the steps of acute inflammation
A
- Vascular changes - vasodilation! ∴ ↑ vessel flow
- ↑ Vessel permeability ∴ formation of fluid exudate
- Formation of cellular exudate - neutrophil polymorphs emigrate into extravascular space
7
Q
What are the potential outcomes of acute inflammation?
A
- Resolution
- Suppuration - pus formation
- Organisation - healing via fibrosis
- Progression to chronic inflammation
8
Q
5 Cardinal signs of inflammation
A
- Rubor (redness)
- Calor (heat)
- Tumor (swelling)
- Dolor (pain)
- Functio laesa (loss of function)
9
Q
Rubor is due to
A
dilation of capillaries within damaged area
10
Q
Calor is due to
A
Increased blood flow to damaged region
Results in vascular dilation
∴ more warm blood to region
Also, maybe systemic fever
11
Q
Tumor is due to
A
Oedema!
(fluid accumulates in extravascular space)
+ formation of new connective tissue
Also, maybe mass of inflammatory cells migrating into region
12
Q
Dolor is due to
A
Stretching of tissue due to inflammatory odema
+ pus under pressure in abscess cavity
Also, chemical mediators of acute inflammation are known to cause pain
e.g. bradykinin, prostaglandins, serotonin
13
Q
Functio laesa (loss of function) due to
A
Conscious and reflexly inhibited by pain
+ severe swelling may immobilise tissue
14
Q
What cellular component is essential for a histological diagnosis of acute inflammation?
A
ACCUMULATION of neutrophil polymorphs
15
Q
How does organisation (healing by fibrosis) work in acute inflammation?
A
Dead tissue and inflammatory exudate first removed from damaged areas BY MACROPHAGES
Defect is then filled by specialised vascular connective tissue (aka GRANULATION TISSUE) - this is organisation
Then granulation tissue gradually produces collagen to form fibrous scar
16
Q
How do microbial infections cause acute inflammation?
A
VIRUSES - cause death of cells via intracellular multiplication
BACTERIA - release specific eXotoxins, these make chemicals that initiate inflammation
+ release specific enDotoxins, associated w cell walls
17
Q
How do hypersensitivity reactions cause acute inflammation?
A
Altered immunological response cause inappropriate/excess immune response - damages tissues
Cellular or chemical mediators
18
Q
How do physical agents cause acute inflammation?
A
Tissue damage through -
e.g. physical trauma, burns,, radiation (UV), frostbite
19
Q
How do irritant and corrosive chemicals cause acute inflammation?
A
Gross tissue damage (from acids, alkalis etc)
Infecting agents may release specific chemical irritants that cause inflammation directly
20
Q
How does tissue necrosis result in acute inflammation?
A
Tissue death from lack of O2/nutrients
∴ infarction
^ potential inflammatory stimulus due to peptides released from dead tissue
21
Q
What accumulates in the extracellular space of damaged tissue in the early stages of acute inflammation?
A
Oedema fluid
Fibrin
Neutrophil polymorphs
22
Q
Smooth muscle of arteriolar walls form __________ to regulate blood flow through the capillary bed
A
Pre-capillary sphincters
23
Q
What happens to the pre-capillary sphincters in arteriolar walls in acute inflammation?
A
Relax
∴ ↑ Blood flow through capillaries
24
Q
How is capillary hydrostatic pressure and therefore, osmosis into the extravascular space changed during acute inflammation?
What happens to the vascular permeability?
A
Pressure increased
∴ increasing osmotic pressure
∴ more fluid leaving vessels than returned
∴ ↑ Vascular permeability
25
Net escape of protein-rich fluid from capillaries is called?
Hence, what is the fluid called?
Exudation
Fluid exudate
26
3 Types of causes of ↑ Vascular permeability?
Give examples
1. Immediate transient - chemical mediators e.g. histamine, nitric oxide (vasodilator), platelet activating factor
2. Immediate sustained - severe vascular injury i.e. trauma
3. Delayed prolonged - endothelial cell injury e.g. X-rays, bacterial toxins
27
Name the 4 stages of neutrophil polymorph emigration
1. Margination of neutrophils
2. Adhesion of neutrophils
3. Neutrophil emigration
4. Diapedesis
28
Describe the 1st stage of neutrophil polymorph emigration
**1. Margination of neutrophils**
NORMALLY, cells confined to central (axial) stream
HOWEVER, in acute inflammation, ↓ intravascular fluid and ↑ plasma viscosity
∴ cells flow in plasmatic zone! (to the side)
29
Describe the 2nd stage of neutrophil polymorph emigration
**2. Adhesion of neutrophils**
NORMALLY, neutrophils randomly contact endothelium but do NOT adhere
HOWEVER, in acute inflammation, at sites of injury pavementing occurs early - ONLY IN VENULES.
30
What is pavementing?
Adhesion of neutrophils to the vascular endothelium
31
Describe the 3rd stage of neutrophil polymorph emigration
**Neutrophil emigration**
Leucocytes migrate through walls of venules/small veins
NOT usually through capillaries !
Neutrophils, eosinophil polymorphs and macrophages all insert _pseudopodia_ between endothelial cells.
Then these cells migrate through created gap
Then through basal lamina into vessel wall.
32
Describe the 4th stage of neutrophil polymorph emigration
**Diapedesis**
RBCs also escape from vessel but this is PASSIVE
∴ depends on hydrostatic pressure forcing RBCs out = diapedesis
33
What does a large number of RBCs in the extracellular space indicate?
Severe vascular injury e.g. tear in vessel wall
34
How does the acute inflammation response spread?
Chemical substances from injured tissue spreads outwards into uninjured area
35
Early in response, what causes the up-regulation of adhesion molecules on endothelial cell surface?
**Histamine** and **thrombin** which is released by initial inflammatory response
36
What do endogenous chemical mediators cause?
Vasodilation
Emigration of neutrophils
Chemotaxis
↑ Vascular permeability
Itching & pain
37
What does histamine cause when released from cells during acute inflammation?
Vascular dilation
Immediate transient phase of ↑ vascular permeability
38
How does histamine have an _immediate_ effect on vascular permeability?
Bc it is stored in preformed granules
∴ able to be instantly released
39
What is the key source of histamine?
What are other sources?
Mast cells
Basophils and eosinophil leucocytes, platelets
40
What stimulates the release of histamine from its sources?
C3a & C5a
Lysosomal proteins released from neutrophils
41
Name some chemical mediators, other than histamine
Lysosomal compounds
Eicosanoids
5-hydroxytryptamine (serotonin)
Chemokine
42
How many enzymatic cascade systems does plasma contain? Name them.
1. Complement
2. the Kinins
3. Coagulation factors
4. Fibrinolytic system
All interrelated
43
What is the main purpose of the complement system?
How does it carry this out?
Remove/destroy antigens
Via direct lysis or opsonisation
44
What is opsonisation?
Enhancement of phagocytosis by factors in plasma
45
Describe the kinin system pathway
Activated factor XII and plasmin (also maybe leucocyte protease) activates conversion of prekallikin to kallikrein
This activates conversion of kininogens to kinins e.g. bradykinin
DRAW PICTURE
PAY FOR BRAINSCAPE
46
How do neutrophil polymorphs stain under H&E?
Nucleus stains blue
Cytoplasm stains pink/purple
47
skipped from 15 - 19
48
What are the 4 main outcomes of acute inflammation?
1. Resolution
2. Suppuration
3. Organisation
4. Progression to chronic inflammation
49
What is resolution?
Complete restoration of tissues to normal after acute inflammation
50
What conditions favour resolution?
Minimal cell death/tissue damage
If it happens in an organ that is capable of regeneration e.g. liver
Causal agent is rapidly destroyed
Local vasculature rapidly removes fluid and debris
51
Give an example of an acute inflammatory response that completely resolves
Acute lobar pneumonia
52
What occurs in suppuration?
Formation of pus, cellular debris and lipid globules
53
What condition is necessary for acute inflammation to result in suppuration?
Causative stimulus is persistent and vv likely to be infectious, usually pyogenic bacteria
54
Give an example of pyogenic bacteria
Staph. aureus
Neisseria species
55
What happens in suppuration after pus accumulates in the tissue?
Pus becomes surrounded by 'pyogenic membrane'
This consists of sprouting capillaries, neutrophils and fibroblasts
Start of healing - results in granulation tissue and scarring
56
What is a collection of pus known as?
An abscess
57
Why is an abscess a bit of a problem?
Bc bacteria within cavity is relatively inaccessible to antibodies and antibiotics
58
What is organisation?
Describe the process
Tissue being replaced by granulation tissue to repair them
New capillaries grow into inflammatory exudate
Macrophages emigrate into area and fibroblasts proliferate (by TGF-beta)
∴ fibrosis and scar formation
59
What conditions favour organisation?
When large amounts of fibrin produced - cannot all be removed by fibrinolytic enzymes from plasma/neutrophil polymorphs
Lots of tissue becomes necrotic or dead tissue cannot be digested
Exudate/debris cannot be removed
60
Why can acute inflammation sometimes progress to chronic?
if causing agent isn't removed
61
What happens during the progression of acute to chronic inflammation?
Cellular exudate changes
**Neutrophil polymorphs REPLACED** by lymphocytes, plasma cells, macrophages, multinucleate giant cells and fibroblasts
62
Name a systemic effect of inflammation
Fever (Pyrexia)
63
What causes pyrexia during inflammation?
Endogenous pyrogens act on hypothalamus, causes higher temp
64
Which endogenous pyrogen has the greatest effect on pyrexia?
Interleukin-2 (IL2)
65
What produces pyrogens?
What stimulates their release?
Produces : Neutrophil polymorphs & macrophages
Stimulates release : Phagocytosis, endotoxins and immune complexes
66
Why is weight loss a symptom of chronic inflammation?
**negative nitrogen balance**
bc lots of energy req to produce inflammatory mediators
67
What is likely to be the cause of inflammation with an increased amount of **eosinophils** in the blood?
Allergies and parasitic infections
68
What is likely to be the cause of inflammation with an increased amount of **neutrophils** in the blood?
pyogenic infections & tissue destruction
69
What is likely to be the cause of inflammation with an increased amount of **lymphcytes** in the blood?
Chronic infection, viral infections and whooping cough
70
What is likely to be the cause of inflammation with an increased amount of **monocytes** in the blood?
Bacterial infections e.g. TB, typhoid
71
What is one potential result of long-standing chronic inflammation?
↑↑ SAA (serum amyloid A protein)
∴ ↑ amyloid deposit in tissue/organs
∴ secondary amyloidosis
72
Define chronic inflammation
Prolonged tissue reaction to injury following initial response
Lymphocytes, plasma cells and macrophages predominate
73
What's an example of a chronic abscess?
Why is this difficult to get rid of?
Abscess in the bone
difficult because bone has poor access to macrophages
74
*
The presence of what materials favours chronic inflammation with an abscess? Why?
Indigestible materials e.g. keratin or fragments of necrotic bone
Bc materials are resistant to lysosomal enzymes
75
What causes granulomatous inflammation?
What further impact do they have on macrophages?
Foreign bodies e.g. wood, metal, glass etc
Cause macrophages to form multinucleate giant cells
76
What is an example of recurrent episodes of acute inflammation resulting in chronic inflammation?
Chronic cholecystitis from gallstones
77
Describe the macroscopic features in chronic inflammation
Chronic ulcer
Chronic abscess cavity
Thickened wall of hollow organ
Granulomatous inflammation
Fibrosis
78
Describe the microscope features in chronic inflammation
**Cellular infiltrate usually has lymphocytes, plasma cells & macrophages**
NO neutrophil polymorphs, sometimes will have eosinophil polymorphs
Some macrophages may form multinucleate giant cells
Maybe new fibrous tissue
Tissue necrosis, esp in granulomatous conditions
79
How do macrophages move through tissue?
Amoeboid motion
80
go over page 26+27
81
Name some important cytokines produced by macrophages
Interferon-alpha & -beta
Interleukin-1, 6 & 8
TNF-a
82
What is a granuloma?
An aggregate of epithelioid histiocytes formed in response to chronic inflammation
83
What is the most common cause of granulomas?
Tuberculosis
84
Describe the features of epithelioid histiocytes
Large vesicular nuclei
Lots of eosinophilic cytoplasm
Elongated
Little phagocytic activity
85
What aspect of epithelioid histiocytes can act as a marker for disease? What type of disease?
Secretes enzymes - one being angiotensin converting enzyme (ACE)
If measure ACE levels, can act as a marker for systemic granulomatous diseases
e.g. sarcoidosis
86
skipped from 28 - 37
do all this but later
87
Give examples of cells that DO regenerate
Hepatocytes
Pneumocytes
ALL blood cells
Gut epithelium
Skin epithelium
Osteocytes
88
Give examples of cells that do NOT regenerate
Myocardial cells
Neurons
89
Define thrombosis
When blood contents formed _within_ vascular system during life solidify
90
Define a clot
Blood coagulates outside of vascular system OR after death
91
Why don't thrombus' form all the time?
Bc of **laminar flow** - cells travel in centre of vessels i.e. don't touch the sides!
Also, bc endothelial cells are not sticky if healthy!
92
Where are platelets derived from?
Bone marrow cells - megakaryocytes
93
What's a distinguishing feature of platelets?
NO nucleus
94
State the types of granules platelets contain and their function
Alpha granules - contain substances that help platelets stick to damaged vessel wall
Dense granules - help platelets to aggregate
95
When are the contents of platelet granules released?
When platelet comes into contact w/ collagen (which is found in vessel walls)
96
Thrombosis is caused by which 3 factors?
Virchow's triad
1. Changes in vessel wall
2. Changes in blood flow
3. Changes in blood constituents
All 3 not req, any one can result in thrombosis
97
Describe the first stage of thrombosis
**Platelet aggregation**
this then starts clotting cascade
98
Why is platelet aggregation and the clotting cascade difficult to stop?
Bc they are both positive feedback loops
99
By what protein molecule are RBCs entrapped during thrombosis?
Fibrin
100
Why does an atheromatous plaque result in a thrombus?
Bc change in vessel wall AND change in blood flow
101
describe the process of arterial thrombus
fatty streak etc p38
102
Where do most venous thrombi occur?
Why?
Usually begin at valves
Bc valves create turbulence bc protrude into vessel lumen
easily damaged by trauma, stasis or occlusion
103
Which side of a venous thrombus is the turbulence greatest?
Upstream side
104
What is venous return from the legs dependent on?
∴ what risk factor does this create?
Calf muscle contraction and relaxation
∴ if people are immobilised (esp elderly) creates a higher risk of formation of DVT
105
How does arterial thrombosis present?
Loss of pulse distal to thrombus
Area becomes cold, pale and painful
Eventually, the tissue will die and gangrene occurs
106
How does venous thrombosis present?
Area becomes tender & general ischaemic pain
Area becomes red and swollen
107
What are the 4 potential outcomes of thrombosis? (& brief description)
**PICTURE**
**1. Lysis and resolution** - body dissolves it and clears it away
**2. Organisation** - may become organised into a scar. macrophages clear away thrombus and fibroblasts replace it with collagen ∴ vessel slightly narrows.
**3. Recanalisation** - Intimal cells of vessel proliferate. Small capillaries grow into thrombus and fuse, creates large vessels.
∴ OG occlusion is recanalised and vessel is functional again
**4. Embolism**
108
What is the term for when RBCs flow in the middle of the arteries?
Laminar flow
109
Why can aspirin prevent thrombosis?
It inhibits platelet aggregation
∴ low dose can be used to prevent thrombosis
110
What can be used in severe cases to prevent thrombosis? Why?
Warfarin bc inhibits Vitamin K (clotting factor)
111
What is an embolus?
Mass of material in vascular system able to lodge in a vessel and block its lumen
Usually broken off piece from thrombus
112
Other than a thrombus, what are some less common causes of an embolus?
Air - IV fluids/bloods, esp in children
Cholesterol crystal - from atheromatous plaques
Tumour amniotic fluid - rare, pregnant women w rapid labour
Fat - severe trauma w multiple fractures
113
How does a pulmonary embolism occur?
Embolus enters venous system -> vena cava -> R heart -> lodges in pulmonary arteries
114
Why can't a venous embolus enter the arterial circulation?
Bc capillaries in lungs too narrow for it to pass through
∴ lungs act as a filter
115
If a venous embolus DOES enter the arterial circulation, what does this indicate?
Perforated septum in heart
116
How do small emboli present?
Usually unnoticed and are lysed by lung
MIGHT become organised and cause permanent but small damage
Over time might cause idiopathic pulmonary hypertension
117
How do mid-sized emboli present?
Chest pain, shortness of breath
MIGHT be large enough to cause actue resp and cardiac problems - could resolve with/without treatment _slowly_
Lung function is impaired and at higher risk of future emboli
118
How do massive emboli present?
Result in sudden death
Often impacted at bifurcation of major pulmonary arteries
119
When can a thrombus form on areas of cardiac muscle?
When muscle has died from MI
bc these areas have lost endothelial lining ∴ exposing collagen to circulating platelets
OR
AF - causes blood to stagnate ∴ thrombus
when normal heart rhythm is back, thrombus breaks off and forms embolus
120
What does the reversibility of ischaemia on tissues depend on?
Duration of ischaemia - if brief, could be reversed
Metabolic demands of tissue - i.e. cardiac myocytes and cerebral neurones esp vulnerable
121
Define ischaemia
Reduction in blood flow to tissue/part of body caused by constriction or blockage of blood vessels supplying it
122
Define infarction
NECROSIS of part/whole organ when artery supplying it is obstructed
123
Why are organs esp vulnerable to infarction?
Bc most organs have only one artery supplying them
124
What organs have dual arterial supply?
Name the supply
Liver - portal venous and hepatic artery
Lung - Pulmonary venous and bronchial artery
Brain - circle of Willis
125
What is reperfusion injury?
Very common
Tissue damage doesn't occur until perfusion is re-established
bc damage is usually O2 dependent ∴ has to wait till blood flows back to organ.
Area of tissue that was ischaemic has been damaged - transport mechanisms across membrane disrupted - esp calcium out of cell
∴ mitochondria impaired
This triggers activation of O2-dependent free radical system to clear dead cells!
-> hallmark of reperfusion injury
ALSO, neutrophil polymorphs and macrophages enters area and clears away debris
imports own free-rads into area
∴ more damage
126
Define Gangrene
Whole areas of limb/region of gut have arterial supply cut off
∴ Large areas of mixed tissues die in bulk
127
Types of gangrene
Brief description
**Dry gangrene** - Tissue dies, healing occurs above. Eventually, dead area drops off.
Sterile process.
Commonly found in gangrenous toes as complication of diabetes.
**Wet gangrene** - Bacterial infection is a 2° complication. Gangrene spreads proximally, patient dies from sepsis
128
Describe Disseminated Intravascular Coagulation (DIC)
Thrombosis without counterbalance
∴ small thrombi form throughout body
∴ bleeding occurs at multiple places bc these thrombi use all the clotting factors (consumption of clotting factors)
129
What is a watershed area?
Tissue that is at the adjacent territory of 2 arteries (supplied by both)
130
Why is a watershed area vulnerable to infarction during hypofusion?
Bc it's supplied by distal end of arteries ∴ less likely to receive sufficient blood during hypofusion
However, not vulnerable during atherosclerosis bc 2 artery supply
131
Give 3 examples of a watershed area
1. Splenic flexure of colon
2. Regions of cerebral hemispheres
3. Myocardium between endocardium and myocardium perfused by coronary arteries
132
Other than thrombi, state and describe some other causes of ischaemia/infarction
**Spasms** - spasm in smooth muscle in vessel wall.
Happens bc ↓ of nitric oxide by vascular endothelium bc cellular injury
Occurs in angina
**External compression** - Veins more susceptible to occlusion this way
Occurs in strangulated hernias, testicular torsion, torsion of ovaries
**Steal syndromes** - when blood is diverted from vital territory
Blood will divert away from atheromatous vessel ∴ territory supplied by that vessel becomes ischaemic
**Hyperviscosity** - Increased blood viscosity, most impact on small vessels
Occurs in myeloma
**Vasculitis** - Inflammation of vessel wall narrows lumen
PICTURES !!
133
skipped from 49 - 56
Atherosclerosis - rlly cba
& Aneurysms/strokes etc
don't want that right now
134
What is Apoptosis?
Intended programmed cell death
135
Where does apoptosis regularly occur in the body?
In the gut - duodenum
Individual cells of gut villi apoptose and are replaced
136
What are some inhibitors of apoptosis?
Growth factors
Extracellular cell matrix
Sex steroids
Viral proteins
137
What are some inducers of apoptosis?
WITHDRAWAL of growth factors
LOSS of matrix attachment
Glucocorticoids
Some viruses
Free radicals
DNA damage
138
Describe the intrinsic and extrinsic pathway of Apoptosis
draw a diagram i think
139
What factors influence tumour invasion?
↓ Cellular adhesion
Secretion of proteolytic enzymes
Abnormal or ↑ Cellular motility
140
What does altered expression of adhesion molecules cause?
Decreased cell-cell adhesion in carcinomas
∴ allows them to escape from site of origin
i.e. metastasise
141
How is the cellular motility of neoplasms abnormal?
More motile
Shows loss of normal mechanism that stops or reverses normal cellular migration
142
What are the most important proteinases in neoplastic invasion?
Matrix metalloproteinases
143
How are matrix metalloproteinases secreted?
How is this useful?
By malignant neoplastic cells, enables them to digest surrounding connective tissue
144
What are the 2 types of Autopsy?
Hospital autopsies
Medico-legal autopsies
145
Which is the most common type of autopsy?
Medico-legal
146
When are hospital autopsies useful?
Audit
Teaching
Governance
Research
147
What is the Human Tissue Act 2004?
Autopsies only happen on licensed premises
Consent from relative for use of tissue retained at autopsy if not subject to coronial legislation or retained for criminal justice purposes
Public display requires consent from deceased
If you don't follow the Human Tissue Act, penalties include up to 3 years of imprisonment and/or fine
148
What are the types of death referred to by coroners?
**Presumed natural** - cause of death not known, not seen by a doctor in the last 14 days for illness
**Presumed iatrogenic** - anaesthetic deaths, abortion, complications of therapy, peri/postoperative
**Presumed unnatural** - accidents, suicide, industrial death, unlawful killing, neglect, custody deaths
149
What is the Coroners Act 1988?
Allows coroners to order autopsy when death is likely due to natural causes to obviate need for inquest.
Also allows coroners to order autopsy where death is unnatural and inquest is needed
150
What is the Coroners Rules 1984?
Autopsy ASAP by pathologist of suitable qualification and experience
Report findings ONLY to coroner
Autopsy only on appropriate premises
151
What is the Amendment Rules 2005?
Pathologist must tell coroner what materials have been retained
Coroner authorises retention and sets disposal date, also informs family of retention
& Family has choice of :
Return material to family
Retain for research/teaching
Respectful disposal
Coroner informs pathologist of family's decision
152
What is the Coroners and Justice Act 2009?
Coroner can now defer opening the inquest and launch an investigation instead
Inquests not have conclusions, not verdicts
153
What does Virchow's triad describe?
The factors contributing to thrombosis
154
State the 3 factors in Virchow's triad
Stasis of blood flow
Endothelial injury
Hypercoagulability
OR
Change in blood flow
Change in vessel wall
Change in blood constituents
155
