Basic Principles Of Pathobiology Flashcards
(135 cards)
1
Q
What are the 4 basic cellular functions that molecular adaptations may affect?
A
1) . Synthesis
2) . Secretion
3) . Enzyme function
4) . Activation of proteins
2
Q
What are 5 basic cellular changes that may occur in response to disease?
A
1) . Changes in proliferation
2) . Changes in size
3) . Changes in apoptosis
4) . Changes in differentiation
5) . Changes in migration
3
Q
What are the main organ changes that may occur in response to disease?
A
Hypertrophy or atrophy, Hyperplasia or involution, Metaplasia, Fibrosis, Neoplasia.
4
Q
What kinds of environmental changes may a cell be exposed to?
A
Environmental stimuli may be physiological or pathological.
Changes that may be physiological or pathological include nutritional changes, immune changes, endocrine changes and physical agents.
Pathological changes include those caused by chemical agents, infections, anoxia and genetic factors.
5
Q
If environmental stimuli are causing an increase in functional demand what might the cellular response be?
A
If the environmental stimuli is causing an increase in functional demand this can be met by two main responses, hypertrophy and hyperplasia. These may occur independently or together. This will be reflected by the increase in size/weight of an organ.
6
Q
Give an example of an environmental stimuli that can lead to increased functional demand.
A
One example of a stimuli that can lead to an increased functional demand is increased growth factors (e.g. due to a tumour producing growth factors). Growth factors and their receptors control cell growth. In disease cellular adaptations are controlled by the actions of growth factors linking to nuclear transcription factors via a secondary messenger system.
7
Q
Give an example of physiological hypertrophy.
A
Skeletal muscle hypertrophy in response to exercise.
8
Q
Give an example of pathological hypertrophy.
A
Pathological hypertrophy of the myocardium in hypertensive heart disease.
9
Q
Give an example of physiological hyperplasia.
A
Physiological hyperplasia of the endometrium in the menstrual cycle (driven by oestrogen).
10
Q
Give an example of pathological hyperplasia.
A
Pathological hyperplasia occurs in skin after trauma (e.g. calluses).
11
Q
What kind of hyperplasia may be seen in the breast and prostate?
A
Nodular hyperplasia. It may occur in a non-uniform pattern.
Nodular hyperplasia in prostate can cause obstruction.
12
Q
If there is a decrease in functional demand the cell stress response may be initiated. What is the cell stress response?
A
The cell stress response allows cells to survive pathological stimuli. Housekeeping genes are switched off and cell stress genes are switched on.
Cell stress proteins are cryoprotective proteins expressed in the cells.
One example of cell stress proteins are the cell stress proteins that act as molecular chaperones and prevent misfolding of proteins.
13
Q
Describe the cell stress responses to damaging stimuli including the ubiquitin system and autophagy.
A
The ubiquitin system. Ubiquitin tagging usually deals with damaged and misfolded proteins and results in them being escorted to the proteosome.
When you get damaging stimuli resulting in reduction of cellular demand you may get cellular atrophy. Cell components are removed by degradative systems such as cytosolic proteolysis via the ubiquitin system.
You may also get autophagy of organelles whereby elements are enwrapped by internal membrane system and fused with the lysosomal system for degradation.
One of the manifestations of autophagy is the production of vacuoles containing lipid material. This is seen as a brown material termed lipofuscin and is caused by indigestible bodies.
14
Q
What is one of the manifestations of autophagy that can be seen microscopically?
A
One of the manifestations of autophagy is the production of vacuoles containing lipid material. This is seen as a brown material termed lipofuscin and is caused by indigestible bodies.
15
Q
Decreased functional demand due to environmental stimuli can lead to apoptosis. Describe the basic process of apoptosis.
A
Certain tropic signals can lead to cells death via apoptosis. This is brought about by a precise cellular system.
1) . Cells round lose contact, round up and nuclear condensation takes place.
2) . Apoptotic cells undergoes fragmentation to form apoptotic bodies.
3) . Apoptotic fragments are recognised by adjacent cells and internalised and degraded,
Apoptosis is programmed, organised destruction without the release of cellular content into the environment.
Cell death pathway exists in the cell metabolism controlled by the action of protease enzymes termed caspases. DNA is cleaved into fragments in between nucleosomes by endonucleases. Protein in cells is cross linked by transglutaminases.
16
Q
How can apoptosis pathways be triggered?
A
1) . Surface receptor activation
2) . Surface membrane damage
3) . DNA damage - p53 is activating by DNA damage and then either activates DNA repair or apoptosis depending on the level of damage.
17
Q
Whether a cell lives or dies depends on the balance between _________ and ________ signals.
A
Whether a cell lives or dies depends on the balance between pro apoptotic and anti apoptotic signals.
18
Q
Reduced demand for cell activity can lead to atrophy. What is atrophy?
A
Atrophy is the reduction in cell volume and reduction in cell number.
Cell loss is commonly replaced by either adipose or fibrous tissue.
Atrophy is reflected in a reduced size and mass of organ.
19
Q
What are some common causes of atrophy?
A
Denervation, Immobilisation, Reduced endocrine stimulation, Ischaemia, Ageing
20
Q
Give an example of pathological atrophy.
A
Atrophy in denervated skeletal muscle due to reduction in trophic factors that nerves give to muscles. Loss of growth factors leads to a decrease in muscle mass.
Disuse of muscles can also lead to atrophy.
21
Q
What are some causes of small organs other than atrophy?
A
Hypoplasia - incomplete organ growth.
Agenesis - complete failure of organ to develop during embryogenesis.
22
Q
What is physiological atrophy termed?
A
Involution.
23
Q
Give some examples of involution.
A
Most instances of involution are the result of withdrawal of an endocrine stimulus.
E.g. Breast involution after cessation of lactation.
Uterus after parturition.
Thymus involution post puberty.
24
Q
Give some examples of where metaplasia occurs.
A
Bladder stones can cause increased pressure on bladder walls and cause transitional epithelium to change to squamous epithelium.
Oesophageal squamous epithelium changes to columnar epithelium in response to acid reflux in a process called Barrett’s metaplasia. This is associated with an increased risk of oesophageal adenocarcinoma.
Columnar epithelia can change to squamous epithelia in the lungs due to smoking.
Trauma may result in collagenous tissue converting to osseous tissue.
In the uterine cervix during growth columnar epithelia converts to squamous epithelia.
25
What is the basic flow of events in cellular adaptations to disease?
Pathological stimuli / environmental stimuli / pathological stimuli >>> molecular changes >>> cellular changes >>> organ changes.
Cell changes can only go in a limited number of directions.
26
What will dictate the cellular response to injury?
Nature of stimulus,
Magnitude of stimulus,
Nature of the cell (robust or vulnerable)
27
List some of the possible causes of cell damage.
```
Hypoxia,
Toxins,
Metabolic causes,
Infections,
Ischaemia,
Physical agents.
```
28
What is ischaemia?
Ischaemia is the failure of blood supply to a tissue or organ. May be caused by vessel blockage or severely reduced blood pressure. Cells exposed to ischaemia develop abnormalities in multiple cell systems such as mitochondria (can lead to depletion of ATP, membrane ion pumps, protein synthesis and fall in pH).
29
How might a cell respond to sub-lethal damage?
Cells exposed to deleterious changes in their environment may start to fail. Cell failure can manifest in structural changes. These changes are called cellular degenerations and are potentially recoverable.
One of the manifestations of injury is vacuolation. In a damaged cell the mechanisms which maintain ion pups may fail. This can result in water being retained by the cell. The membrane systems become dilated with fluid and the cells become vacuolated and pale-stained.
30
What is a vacuole? What do physiological vacuoles contain? What do pathological vacuoles usually contain?
A vacuole is a large space within a cell filled with a substance. A cell is said to show vacuolation when it has developed vacuoles. Examples of normal vacuolation include mucin and glycogen vacuolation. Pathological vacuoles often contain water.
31
What is hydropic vacuolation?
A cell which is severely vacuolated as a result of pathological fluid accumulation is said to have undergone hydropic degeneration.
32
I which tissues might hydropic degeneration be seen?
Hydropic degeneration is not seen in all tissues but is seen in the liver and renal tubules.
33
In addition to hydropic vacuolation, sub-lethal damage in some cell types can cause fatty change. What is fatty change?
Another manifestation of pathological vacuolation is fatty change. Sub lethal damage in some cell types may alter the metabolism of the cell. The cell then accumulates triglycerides. The accumulated fat distends the cytoplasm of the cell. The accumulated fat forms vacuoles in a process termed fatty change,
34
What is the commonest example of fatty change?
The commonest example of fatty change is seen on the liver in response to ethanol.
35
What are some causes of fatty change?
Ethanol in the liver.
Hypoxia, diabetes, toxins, malnutrition.
36
Where might fatty change be seen other than in the liver?
Fatty change is also seen on some conditions in renal tubual epithelial cells and some cardiac muscle cells.
37
What does fatty change look like under the microscope?
It looks similar to hydropic change because neither water or fat stain.
38
What happens in sub lethal cellular injury when the pathological stimulus is removed?
With sub lethal injury when the stimulus is removed the various damaged cellular components can undergo autophagy, proteolysis, re synthesis and the cell can recover. Residual materials may remain as inclusion bodies (stigmata of damage). For example lipofuscin bodies.
39
What might happen to the cell if the cellular damage is severe or maintained?
If cellular damage is severe or maintained it may lead to cell death.
Cell death may occur in the form of tissue necrosis which is typically uncontrolled.
Macroscopically different types of necrosis can be seen depending aetiology.
Cell death may also occur as apoptosis.
40
What type of cell death can massive instant damage lead to? What type of stimulus can cause this type of cell damage?
Massive damage can lead to instant cell death which can result in coagulated necrosis where the proteins all become coagulated.
Some stimuli such as extreme heat, extreme pH change can cause proteins to instantly coagulate. It is a relatively uncommon clinical situation.
41
What happens if cell damage is above a level from which it is capable of recovery (but not massive instant damage)?
Liquefactive necrosis takes place. Cell death is followed by a series of structural changes called necrosis.
Liquefactive necrosis is the most common form of necrosis.
42
What happens in liquefaction necrosis? What brings about the changes that occur in necrosis?
In liquefactive necrosis cell death is accompanied by spillage of cellular components into the environment. These components can affect adjacent cells.
As part of necrosis you get pyknosis where the nucleus shrinks and begins to break up. Eventually the nucleus will break up via karyorrhexis. This happens rapidly in an uncontrollable manner. Unlike the controlled condensation of apoptosis. Cell then essentially becomes a liquified mess.
Most of the changes in necrosis are brought about by disruption of internal membrane systems. Release of lysosomal hydrolase brings about cell structural changes. Membrane loss allows proteins to leak from the cells into the tissue fluids, eventually being detected on blood. Blood tests can be a measure of tissue damage.
Look at the schematic of necrosis.
43
What are the consequences of necrosis?
Necrosis stimulates a tissue response to injury,
Necrosis stimulates cell proteins into tissue fluids,
The tissue response to injury recruits neutrophils and other cells in a process called inflammation (have local and long range neutrophil recruitment effects). Inflammation aims to limit the amount of damage caused by prolonged stimulus.
44
What processes may initiate apoptosis?
Surface receptor activation,
Surface membrane damage,
Mitochondrial membrane damage,
DNA damage.
45
Does apoptosis result in the spillage of cellular contents into the environment?
No. Apoptosis is programmed cell death. It is more ordered and there is no spillage of content into the environment.
Cells are broken up into small fragments which are then internalised and processed by adjacent cells.
46
What are the benefits of apoptosis over necrosis?
Damaged cells are removed cleanly,
| Does not stimulate a tissue response to injury.
47
How can patterns of necrosis be used to indicate the cause of a disease process?
Tissue patterns of necrosis can be seen at a macroscopic and histological level. These different patterns of necrosis are associated with different causes.
Identification of a specific pattern of necrosis in a tissue biopsy may indicate the cause of the disease process.
48
What does coagulative necrosis look like histologically?
Coagulative necrosis shows cell and tissue outlines preserved but complete loss of cellular features.
49
What is the most common cause of coagulative necrosis?
Sudden rapid ischaemia.
50
What does liquefactive necrosis look like histologically?
No normal tissue remains in liquefactive necrosis, just sheets of macrophages.
Tissue architecture is effaced rapidly leaving liquid material and macrophages. Due to release of hydrolytic enzymes. Frequently occurs in the brain, you get an inflammation response and neutrophils recruited which then undergo necrosis.
51
What does caseous necrosis look like under histological examination?
Caseous necrosis macroscopically looks like cheese.
Sheets of homogenous unstructured, proteinase material.
Frequently seen in TB and other mycobacterial infections.
52
How does gummatous necrosis appear on histological examination?
Rubbery, firm texture,
Densely packed proteinaceous material,
May be caused by Treponema Pallidum (Syphilis),
Rare in UK.
53
What can cause gummatous necrosis?
Treponema Pallidum (syphylis)
54
What can cause caseous necrosis?
Tuberculosis.
55
What can cause haemorrhagic necrosis? What does this look like histologically?
Often caused by venous obstruction, blocking or twisting of veins.
Tissue suffused with blood. There is red cell extravastaion (leakage out of vessels).
Caused by complete venous obstruction.
56
What does fibrinoid necrosis look like histologically?
The term is limited to vascular structures. The cell wall is replaced by fibrin-like material.
57
What is fibrinoid necrosis caused by?
Firbrinoid necrosis is caused by severe hypertension, vascular is and radiation damage.
58
What determines progress to apoptosis or necrosis?
Integrity of mitochondria probably determines the fate of a damaged cell.
Cytochrome-c and other factors leak from impaired mitochondria and cause apoptosis.
If there is catastrophic failure of ATP production by gross mitochondrial damage then necrosis supervenes.
59
What changes might cells subject to sublethal injury display?
Hydropic change,
Fatty change,
Cellular inclusions may be indicative of previous insults.
60
Damaged cells may die by 3 main mechanisms. List these.
1) . Coagulative necrosis (uncommon)
2) . Liquefactive necrosis (very common)
3) . Apoptosis (very common)
61
Patterns of necrosis relate closely to aetiology. What 6 necrosis patterns may be observed histologically?
1) . Coagulative
2) . Liquefactive
3) . Haemorrhagic
4) . Caseous
5) . Gummatous
6) . Fibrinoid
62
What are the 4 signs of acute inflammation?
1) . Calor (heat)
2) . Dolor (pain)
3) . Rubor (redness)
4) . Tumour (mass)
63
What is the most common response of the body tissue to an area of nearby damage?
The acute inflammatory response.
64
What pathological stimuli can cause acute inflammation?
Micro organisms, trauma, ischaemia, chemical damage and radiation damage.
65
What is the purpose of the acute inflammatory response?
The purpose of the acute inflammatory response is to:
Destroy or neutralise the damaging agent,
To liquify and remove dead tissue,
To prepare the damaged area for healing.
66
On a basic level how does the acute inflammatory response function?
The acute inflammatory response functions by the production of an acute inflammatory exudate derived from blood components from capillaries adjacent to the damaged area.
67
What does the acute inflammatory exudate consist of?
The acute inflammatory exudate is derived from blood components from capillaries adjacent to the damaged areas.
The acute inflammatory exudate comprises fluid, fibrin and cells (neutrophils, but also a few macrophages and lymphocytes).
The fluid in the exudate dilutes any toxins present. The fluid also carries nutrients, mediators and antibodies to the site. Fibrin is also brought in. The neutrophils then migrate to the area.
Neutrophils are actively phagocytic of living tissues (e.g. bacteria) but also necrotic debris.
68
What cells are mainly involved in the acute inflammatory response?
Acute inflammation mainly involves neutrophils.
69
Describe the stages in exudate formation.
1). Blood vessels near to damaged tissue become dilated in response to inflammatory mediators. This causes the blood to initially increase, then slow down. The axial flow pattern of blood is lost.
Substances released by dead or dying tissue has an effect on the endothelium of blood vessels. This causes dilation of blood vessels and endothelial swelling and retraction. This causes gaps to form and allows water, salts and protein to leak out into the damaged area. Fibrinogen is an important protein. This leakage also leads to oedema.
2). Migration of cells occurs. Neutrophils marginate and emigrate.
Neutrophils stick to endothelial cells (marginate) and then migrate through the capillary into the damaged area (attracted by chemotactic signals).
Adhesion molecules are expressed by epithelial cells that bind specifically to neutrophils.
70
What are the 4 clinically different types of exudate?
1) . Serous
2) . Purulent
3) . Fibrinous
4) . Fibrino-Purulent
71
What is serous exudate?
Serous exudate is mainly fluid and is not only found in inflammation.
72
What is purulent exudate?
Purulent exudate is always due to inflammation.
73
Is fibrinous exudate always due to inflammation?
No, it can arise with or without inflammation.
74
Is fibrino-purulent exudate always a result of inflammation?
Yes. Fibrino-purulent exudate is always due to inflammation.
75
Give an example of a situation in which exudate occurs without the presence of inflammation.
Hypoproteinaemia
76
What 2 kinds of exudate is always a consequence of inflammation?
Purulent exudate and fibrino-purulent exudate is always a consequence of inflammation.
77
What kind of exudate is found around the heart due to pericarditis?
Serous exudate.
78
What kind of exudate is found in the meninges of the brain due to meningitis?
Purulent exudate.
79
What does the histology of purulent exudate show?
Histology of purulent exudate shows a number of live and dead neutrophils.
80
What kind of exudate displays as a shaggy exudate on the surface of the pericardium?
Fibrinous exudate.
81
How does fibrinous exudate display histologically?
The histology of a fibrinous exudate shows masses of pink-staining fibrin.
82
Describe the process of neutrophil migration out of the capillaries.
Chenoattractants are present on the epithelial cell surface.
Neutrophils are captured on the epithelial cell surface. They then roll along the epithelial cell surface and adhesion increases. Firm adhesion.
Under the influence of chemotactic substances the neutrophils head towards the area of inflammation.
As this is taking place the neutrophils are also undergoing maturation.
83
What are one of the main classes of inflammatory mediators?
Eicosanoids.
84
Describe the production of mediators of inflammation.
1) . Mechanical or chemical stimulation of membrane lipids leads to the production of free Arachdonic Acid under the influence of Phospholipase C and Phospholipase A2.
2) . Free Arachidonic Acid can then undergo conversion via one of two paths.
Under the influence of PGH synthase and Cyclooxygenase it can form Prostaglandins, Prostacyclins and Thromboxanes.
Under the influence of Lypoxygenase it can form Leukotrienes.
85
What catalyses the conversion of membrane lipids into Arachidonic Acid?
Phospholipase C and Phospholipase A2.
86
Arachidonic acid is converted into Prostaglandins, Prostacyclins and Thromboxanes under the influence of which enzymes?
PGH synthase and Cyclooxygenase.
87
Many of the inflammatory mediators are targeted by drugs that reduce inflammation. What is the main class of drugs that function via this mechanism?
NSAIDS.
88
Why does acute inflammation have a systemic effect as well as a local one? What may result from this systemic effect?
Because inflammatory mediators will also get into the systemic blood flow as vessels are leaky. This can cause malaise, fever, pain, rapid pulse and has an effect on the cardiovascular system.
89
What process can cause neutrophil leukocytosis to occur as a result of acute inflammation?
Neutrophil leukocytosis is an increase in white blood cells within the periphery blood.
Neutrophil leukocytosis is a consequence of inflammatory mediators getting into the circulatory blood flow and reaching the bone marrow. This causes an increase in production of the leukocytes and neutrophils which will then migrate the the site of inflammation.
90
Why might you get an elevated erythrocyte sedimentation rate (ESR) when acute inflammation is present?
Because a variety of other factors are also being produced resulting in increased viscosity of the blood.
91
What proteins produced by the liver may be found to be elevated in acute inflammatory reactions?
Increased acute phase proteins such as IL-1 induced by CRP.
Acute phase proteins can be measured as a means of following the acute response.
92
True or false? The macrophages play a key role in the acute inflammatory response.
False. Macrophages only play a very small role in the acute phase response and are usually there as chance events.
93
Resolution is one possible outcome of acute inflammation. What does resolution involve?
The acute inflammatory exudate eliminates damaging agents. The macrophages then remove dead cells and exudate and local cells regrow. The tissue structure and function returns to normal.
Complete resolution is not a common outcome following tissue damage and acute inflammation.
94
What pathological situations can result in resolution?
Acute pneumonia,
Acute tubular necrosis in the kidney,
Sunburn.
95
For resolution to occur there are a number of caveats. List some of these.
Resolution requires minimum damage to architecture.
Resolution requires normal structure and function to be restored.
The best example of acute resolution is in lobular pneumonia. Resolution requires no damage to alveolar wall architecture. Exudate forms in alveolar air sacs then liquified exudate is resorbed and alveolar lining cells regrow.
96
What is an abscess?
An abscess is a large accumulation of liquid purulent exudate (pus) in an area where the tissue damage has led to extensive necrosis.
It becomes walled off in an attempt to limit the spread of inflammation.
97
What are abscesses especially caused by?
Bacteria such as staphylococcus.
98
What is a more likely outcome of acute inflammation than resolution?
Healing by repair.
99
Describe the process of healing by repair.
Once the pathogen is dealt with then repair can begin.
1) . Debris is removed by macrophages.
2) . New vessels are grown by support cells in damaged area (angiogenesis).
3) . Fibroblasts migrate into the area and multiply.
4) . Fibroblasts lay down collagen.
5) . New capillaries regress and then fibroblasts regress.
6) . Granulation tissue (new connective tissue and tiny blood vessels) matures to a collagenous scar. It has a vascular phase, fibrovascular and a collagenous phase.
Granulation is involved in organisation of inflammatory tissue and repair.
100
When might healing by repair occur?
Healing by repair occurs when too much damage has occurred (loss of tissue architecture) for complete resolution to occur.
101
In healing by repair does the new tissue have the same structure and functional capacity as the old tissue?
The formation of a scar following tissue damage is an example of healing by repair.
In contrast to resolution, restoration of normal structure and function of the damaged tissue does not occur.
102
When might chronic inflammation occur?
When a damaging stimulus persists complete healing cannot occur and chronic inflammation (lasting weeks to months) then ensues.
103
In what type of inflammation does damage, organisation and repair occur concurrently?
Chronic inflammation.
104
During chronic inflammation the tissue is infiltrated by what kind of cells?
Population profile changes on chronic inflammation. Tissue is infiltrated by macrophages and immune cells.
105
Will chronic inflammation always heal by scarring?
Yes.
106
What is the main effector cell of chronic inflammation?
Macrophages.
107
What chemotactic stimulus activates macrophages?
Gamma interferon.
108
What role do macrophages play in chronic inflammation?
1) . A phagocytic role
2) . A secretory role - they secrete mediators of inflammation, oxygen metabolites, proteases, hydrolases.
Secrete cytokines such as IL-1 and INF-alpha.
They secrete growth factors such as PDGF, EGF and FGF.
109
What is one common example of chronic inflammation?
Chronic peptic ulcer of the stomach.
110
Describe he process of chronic inflammation that occurs on a chronic peptic ulcer of the stomach.
In a chronic peptic ulcer of the stomach the protective mucosa is damaged thus exposing the sensitive tissues underneath to gastric acid.
Tissue necrosis is followed by acute inflammation with acute exudate formation.
Simultaneous acute inflammatory exudate, vascular granulation tissue, fibrous granulation tissue and fibrous scar. Can never heal completely due to continuous insult. There is a stalemate of damage and repair.
The exudate organises into granulation tissue, but in the meantime more damage has been caused on the surface by more gastric acid.
So long as gastric acid continues to cause damage the lesions cannot complete the process of healing with scar.
111
What are the main 2 principles to remember when thinking about chronic inflammation?
1) . Chronic inflammation occurs when the damaging stimulus cannot be eradicated.
2) . In persisting chronic inflammation there is a stalemate between continuing damage and continuing attempts to repair by fibrous scar formation.
112
In the case of a peptic ulcer what might happen if the gastric acid is removed or neutralised?
The situation gets better and damage stops and the ulcer heals with scar formation.
113
What might happen to a peptic ulcer if gastric acid increases or the repair process is impaired?
The damage overwhelms repair and the ulcer can continue deeper and perforation may occur.
114
In what situations might chronic inflammation occur?
Situations in which the damaging stimulus is not amenable to eradication or neutralisation (e.g. gastric acid).
Situations in which bacteria persists because they are distanced from neutrophils, antibiotics etc.
Situations in which bacteria persist because they are resistant to neutrophil phagocytosis e.g. TB.
115
What is granulomatous inflammation?
Granulomatous inflammation is a special form of chronic inflammation in which macrophages are involved early as part of an immune response.
116
What key feature of granulomatous inflammation is formed by macrophages (in addition to lymphocytes and fibroblasts)?
Granulomas.
Macrophages aggregate around the damaging agent with lymphocytes and fibroblasts forming a granuloma.
Macrophages can fuse together to form giant cells that have even greater activity than normal macrophages.
117
What are the causes of granulomatous inflammation?
1) . Low pathogenicity organisms which excite a type IV immune response.
2) . Organic or inorganic foreign material.
3) . Some fungi.
4) . Sarcoidosis.
5) . Parasites.
118
Give an example of a condition that results on granulomatous inflammation.
Tuberculosis.
Mycobacterium tuberculosis is resistant to destruction by neutrophils but it can be phagocytosed and immobilised by macrophages in a type IV response.
As with all chronic inflammation there is a stalemate,
119
What is a TB granuloma called?
A Tubercle.
120
What pattern of necrosis is seen in TB?
Caseous necrosis.
121
Describe the layers of a tubercle.
Caseous necrosis in the centre surrounded by a layer of activated macrophages, the a layer of lymphocytes and finally a wall of fibroblasts that are trying to wall off the area and prevent it from spreading.
122
What is the outcome of TB dependant on?
The outcome of TB is dependant on the stalemate changing.
123
What is the purpose of a tubercle?
The m.tb is contained in the tubercle and it is prevented from spreading.
124
What can lead to TB getting better?
The fibroblasts around the outside of the tubercle proliferate and they can make a collagenous cell layer and prevent the spread of the organism.
125
What can lead to TB getting worse?
TB can get worse of the inflammatory response isn't effective (bacterial load too great, person becomes debilitated). In these cases necrosis will expand until it cannot be contained by the wall of the tubercle. The bacteria may then spread via lymphatics, veins, bronchi and be carried throughout the body.
126
Describe the basic steps in tissue repair.
1) . Remove debris (macrophages).
2) . Grow new vessels.
3) . Fibroblasts lay down collagen.
4) . Mature collagen.
5) . Granulation tissue matures to scar.
6) . Remodelling in tissue to restore normal architecture.
127
What factors might lead to a wound healing by first intention?
Surgical or inflicted wounds heal by organisation and repair.
In a surgical wound trauma is minimised but there is an acute inflammatory response.
If the edges of the wound are closely apposed, wound is uninflected and there is minimal exudate, then granulation tissue organises exudate and matures to collagenous scar. Scarring will be very limited.
128
Why might a wound heal by second intention? What characterises healing by second intention?
If the damage is extensive with marked tissue destruction and/or super infection then healing is more complex.
Healing occurs by second intention and is characterised by greater amounts of necrotic debris/granulation tissue, greater amounts of tissue remodelling, wound contraction on collagen maturation which may cause distortion of the surrounding tissue.
129
Is the acute inflammatory exudate alway beneficial? Give examples to back up your answer.
The acute inflammatory exudate is not always a good thing. In some cases the exudate itself may actually cause the symptoms.
In pleurisy the shaggy acute inflammatory exudate is fibrous. This causes pleuritic pain.
In meningitis the purulent exudate fills the space under the pia-arachnoid. This can lead to raised intracranial pressure and possibly leads to microthrombosis in small vessels due to increased pressure.
130
What are some of the problems that can arise from healing after chronic inflammation?
Chronic inflammation always heals by scar formation, but the scar is however functionless.
The collagen scar is strong but not elastic, contractile or secretory. It is also not always attractive.
Contraction of the collagen on maturation can cause issues as scar tissue is not elastic.
Adhesions from healing can cause problems. Fibrous adhesions in the bowel can cause obstructions.
131
List the factors that may lead to inadequate healing.
Continuing infection such as wound infection,
Foreign or uncleared necrotic material,
Ischaemia of the region,
Diabetes which can lead to ischaemia and infection,
Denervation of the area because nerves provide trophic factors,
Steroid therapy,
Previous irradiation that has caused damage to blood vessels and potentially ischaemia.
132
How can we help induce good healing?
We can suture wounds,
Give antibiotics in situations with super infection,
Give antacids in peptic ulcer cases.
133
How does healing occur in the brain?
Brain parenchyma does not contain fibroblasts and so cannot make collagen.
Brain necrosis undergoes liquefaction.
Astrocytes proliferate and lay down glial fibres to try and wall off the liquid area.
With a brain infarct the tissue will die and then the macrophages turn it into liquid and phagocytose the debris.
134
Describe the steps in the healing of a bone fracture.
Bone cannot be usefully replaced by a collagen scar. If this does occur it is called fibrous non-union. For functional strength the damaged tissue must be replaced by new bone.
1) . The bone defect is filled with a blood clot (haematoma).
2) . After phagocytosis of debris the haematoma undergoes organisation just like the exudate. The defect is filled by vascular and the fibro-vascular granulation tissue. Osteoprogenitor cells develop and then migrate in.
3) . Osteoprogenitor cells convert to osteoblasts which begin to synthesise osteoid collagen. Osteoid collagen becomes calcified to become woven bone (as new bone is laid down hap-hazzardly).
4) . New bone links up with healthy old bone to re establish bony continuity. Active remodelling of woven bone occurs to form strong lamellar bone.
5) . Remodelling continues to give maximum strength on repaired fractures.
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What are some mechanisms of fatty change?
Increase of free fatty acids due to starvation, diabetes, alcoholism.
Reduction of free fatty acid oxidation due to hypoxia, toxins, alcoholism.
Increase of esterification of free fatty acids into triglycerides due to increased free fatty acids or reduction of their oxidation.
Reduced export of triglycerides due to deficiency of lipid binding apoprotein.
At the beginning hepatic yes present small fat vacuoles in the vicinity of the endoplasmic reticulum called liposomes. These are microvesicular fatty changes. In the late stages, the size of the vacuoles increase pushing the nucleus to the periphery of the cell. These are macrovesicular fatty changes. These vesicles are well delineated and optically empty because fat does not survive tissue processing usually. Large vacuoles may coalesce, producing fatty cysts which are irreversible lesions.
