ICS Flashcards

1
Q

2 types of autopsy

A

Hospital and Medico-legal - coronal and forensic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Types of deaths referred to coroners

A

Presumed natural - not know cod and not seen by doctor with recent illness in last 14 days
Presumed iatrogenic - Peri/post op, abortion, complications
Presumed unnatural - accidents, suicide, murder, neglect etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a coronial autopsy?

A

a systematic scientific examination that helps the coroner determine who the deceased was, when and where they died and how they came about their death.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Who refers the autopsy?

A

Doctors
Registrar of BDM - statutory duty to refer
Others - relatives / police

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Autopsy process

A

Identification
External Examination
Evisceration - y shaped incision
Internal Examination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is inflammation

A

The local physiological response to tissue injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is acute inflammation

A

local physiological initial and transient series of tissue reactions to injury that lasts a few hours to a few days. It has a sudden onset, short duration and usually resolves.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Benefits of inflammation

A

Destruction of invading microorganisms
The walling off of an abscess cavity, thus preventing spread of infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Problems with inflammation

A

An abscess in the brain would act as a space-occupying lesion compressing vital surrounding structures
Fibrosis resulting from chronic inflammation may distort the tissues and permanently alter their function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cells involved in inflammation

A

Neutrophil polymorphs
Macrophages
Lymphocytes
Endothelial cells
Fibroblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What cell is first at the site of acute inflammation that is not present in chronic

A

Neutrophil polymorphs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Steps of acute inflammation

A

Vascular - dilation of vessels
Exudative - vascular leakage of protein rich fluid
Neutrophil polymorph recruitment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Outcomes of acute inflammation

A

Resolution
Suppuration - pus formation e.g. abscess
Organisation - fibrosis
Progression - chronic inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is organisation in acute inflammation

A

Healing by fibrosis where there is substantial damage to CT framework and lacks ability to regenerate.
Dead tissue + exudate removed by macrophages
Then filled with granulation tissue
Then produces collagen to form fibrous collagenous scar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Causes of acute inflammation

A

Microbial infections e.g. viruses
Hypersensitivity reactions e.g. parasites
Physical agents e.g. trauma/ radiation
Chemicals e.g. corrosives/ acids
Bacterial toxins
Tissue necrosis e.g. ischaemic infarction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

3 responses of acute inflammation

A

Changes in vessel calibre and flow
Increased vascular permeability and formation of the fluid exudate
Formation of the cellular exudate – emigration of the neutrophil polymorphs into the extravascular space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Macroscopic appearances of acute inflammation and their causes

A

Rubor redness - dilation of small bv
Calor heat - hyperaemia
Tumor swelling - oedema
Dolor pain - chemical mediators
Loss of function - by pain or swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Causes of inc vascular permeability

A

Immediate transient - chemical mediators
Immediate sustained - severe direct vascular injury
Delayed prolonged - Endothelial cell injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Stages of neutrophil polymorph emigration

A
  1. Margination - neutrophils flow into plasmatic zone due to loss of intravascular fluid and inc in plasma viscocity
  2. Adhesion - vascular endothelium at sites of damage become sticky and neutrophils adhere
  3. Neutrophil emigration - cells involved in inflammation create a gap between enodthelial cells and migrate to the vessel wall
  4. Diapedesis - Red blood cells leave vessels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is histamine released

A

Mast cells degranulating due to C3a and C5a from lysosomal proteins released from neutrophils.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Role of tissue macrophages in acute inflammation

A

Secrete chemical mediators when stim by local infection or injury. Most important IL-1 and TNF-alpha which stimulate histamine and thrombin. Also cause cells to secrete MCP-1 to attract neutrophil polymorphs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Process of vascular changes in acute inflammation

A

In acute inflammation, capillary hydrostatic pressure increased and there is escape of plasma proteins into the extravascular space (due to the increased pressure) thereby increasing osmotic pressure there - this results in much more fluid leaving the vessels than is returned to them - this results in increased vascular permeability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How can histamine act so quickly

A

it is stored in preformed granules and is thus instantly able to be released

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

4 enzymatic cascade systems

A
  1. Complement
  2. the Kinins
  3. Coagulation factors
  4. Fibrinolytic system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the complement system
to remove or destroy antigen, either by direct lysis or by opsonisation (the enhancement of phagocytosis by factors (opsonins) in plasma.
26
What is the kinin system
Activated factor XII and plasmin activate the conversion of prekallikin to kallikrein. This stimulates the conversion of kininogens to kinins, such as bradykinin (causes vasodilation). Prekallikrein can also be activated by leucocyte proteases e.g trypsin:
27
Role of lymphatics in acute inflammation
The terminal lymphatics drain in collecting lymphatics, which have valves and so propel lymph passively, aided by contracting of neighbouring muscles, to the lymph nodes - In acute inflammation the lymphatic channels become dilated as they drain away the oedema fluid of the inflammatory exudate - Antigens are carried to the regional lymph nodes for recognition by lymphocytes
28
Role of mast cells in acute inflammation
On stimulation by the C3a/C5a complement components they release preformed inflammatory mediators (i.e. histamine) stored in their granules and metabolise arachidonic acid into newly synthesised inflammatory mediators such as leukotrienes, prostaglandins and thromboxanes
29
Benefits of fluid exudate
Dilution of toxins Entry of antibodies Transport of drugs to the site where bacteria are multiplying Fibrin formation from exuded fibrinogen which may impede the movement of microorganisms thereby trapping them and thus facilitating phagocytosis. Delivery of nutrients & oxygen Stimulation of immune response
30
Harmful effects of fluid exudate
Digestion of normal tissues Swelling Inappropriate inflammatory response - IgE
31
Systemic effects of acute inflammation
Pyrexia - fever Neutrophil polymorphs & macrophages produce compounds known as endogenous pyrogens which act on the hypothalamus to set the thermoregulatory mechanisms at a higher temperature Also anorexia, nausea and weight loss
32
What do Th1 cells do
Cytokine IFN-gamma via classical pathway activate macrophages
33
What do Th2 cells do
Secrete IL-4, 5 and 13 Via alternate pathway Activate macrophages and eosinophils
34
What do Th17 cells do
Secrete IL-17 Recruit neutrophils and monocytes
35
What is chronic inflammation
The subsequent and prolonged tissue reactions to injury following the initial response OR inflammatory process which lymphocytes, plasma cells and macrophages predominate
36
Causes of chronic inflammation
- Resistance of infective agent to phagocytosis - tuberculosis, leprosy - Endogenous - necrotic adipose tissue bone -Exogenous - Silica, asbestos - Autoimmune diseases e.g. rheumatoid arthritis or hashimotos thyroiditis - Specific diseases of unknown aetiology - chronic ibd - Primary granulomatous diseases - chrons - Transplant rejection -Acute inflammation
37
Most common type of acute inflammation to develop to chronic
suppurative type - if the pus forms an abscess cavity that is deep-seated, and drainage is delayed or inadequate, then by the time that drainage occurs the abscess will have developed thick walls composed from granulation and fibrous tissues.
38
Macroscopic appearances of chronic inflammation
- Chronic ulcer: * Such as a chronic peptic ulcer of the stomach with breach of the mucosa - Chronic abscess cavity: * For example osteomyelitis - Thickening of the wall of a hollow organ - Granulomatous inflammation: * 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 (a stationary phagocytic cell (macrophage) found in tissue) - Fibrosis: * Thickening or scarring of connective tissue
39
Microscopic features of chronic inflammation
The cellular infiltrate consists characteristically of lymphocytes, plasma cells & macrophages. A few eosinophil polymorphs may be present but neutrophil polymorphs are scarce Some of the macrophages may form multinucleate giant cells Exudation of fluid is not a prominent feature, but there may be production of new fibrous tissue from granulation tissue There may be evidence of continuing destruction of tissue at the same time as tissue regeneration and repair Tissue necrosis may be a prominent feature, especially in granulomatous conditions such as tuberculosis
40
Paracrine stimulation of connective tissue proliferation leads to..
angiogenesis (formation of new blood vessels) followed by fibroblast proliferation and collagen synthesis resulting in granulation tissue
40
Paracrine stimulation of connective tissue proliferation leads to..
angiogenesis (formation of new blood vessels) followed by fibroblast proliferation and collagen synthesis resulting in granulation tissue
41
What does growth factor EGF do
Regeneration of epithelial cells
42
What does growth factor TGF-alpha do
regeneration of epithelial cells
43
What does growth factor TGF-beta do
Stim fibroblast proliferation and collagen synthesis. Controls epithelial regeneration
44
What does growth factor PDGF do
Mitogenic and chemotactic for fibroblasts and smooth muscle cells
45
What does growth factor FGF do
Stim fibroblast proliferation, angiogenesis and epithelial cell regeneration
46
What does growth factor IGF-1 do
Synergistic effect with other growth factors
47
What does TNF do
Stim angiogenesis
48
Two types of lymphocyte in lymphatic tissue infiltrate and their function
B lymphocyte - Which on contact with antigen, become progressively transformed into plasma cells (cells specially adapts for the production of antibodies) T lymphocyte - cell-mediated immunity * On contact with antigen, produce a range of soluble factors called cytokines, with important activities, such as the recruitment & activation of other cell types e.g macrophages etc.
49
Role of macrophages in chronic inflammation
move by amoeboid motion through the tissues and respond to certain chemotactic stimuli. Macrophages can ingest a wider range of materials then can polymorphs and, being long-lived, they can harbour viable organisms if they are unable to kill them by their lysosomal enzymes When macrophages participate in the delayed-type hypersensitivity response to these types of organism, they often die in the process, contributing to the large areas of necrosis by release of their lysosomal enzymes Macrophages in inflamed tissue are derived from blood monocytes that have migrated out of vessels and have become transformed in the tissues they are thus part of the mononuclear phagocyte system also known as the reticuloendothelial system.
50
What is a granuloma
an aggregate of epithelioid histiocytes TUBERCULOSIS most common
51
How to identify granuloma histologically
Use Ziehl-neelson stain and will be bright red
52
Causes of granulomas
Specific infections - mycobacteria Materials that resist digestion Specific chemicals - beryllium Drugs Unknown - chrons and sarcoidosis
53
What are histolytic giant cells
form where particulate matter that is indigestible by macrophages accumulates when two or more macrophages attempt simultaneously to engulf the same particle; their cell membranes fuse and the cells unite
54
What are langerhans giant cells
horseshoe arrangement of peripheral nuclei at one pole of the cell - Characteristically seen in TUBERCULOSIS
55
What are foreign body giant cells
Large cells with nuclei randomly scattered throughout their cytoplasm Characteristically seen in relation to particulate foreign body material
56
What are Toulon giant cells
Have a central ring of nuclei, peripheral to which there is lipid material Seen when macrophages attempt to ingest lipids and in xanthomas (yellowy patch, can appear anywhere on skin e.g eyelids)/dermatofibromas (fibrous nodule) of the skin
57
Role of acute and chronic inflammation in CV system
Acute in the response to acute myocardial infarction and the generation of some complication of MI such as cardiac rupture Chronic involved in myocardial fibrosis after MI
58
Role of chronic inflammation in cancer
Initiation and propagation and its progression e.g. ulcerative colitis
59
Role of inflammation and atheroma
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
60
Role of chronic inflammation in tissue injury
Multiple sclerosis with chronic demyelinating neurodegenerative disorder in which chronic inflammation
61
Difference between exudate and transudate
Exudate - high protein content due to being from increased vascular permeability Transudate low protein content due to vessels having normal permeability characteristics.
62
Cells involved in cell renewal
Labile cells Stable cell populations Permanent cells Stem cells
63
Where to find stem cells in the body
In the epidermis stem cells are found in the basal layer immediately adjacent to the basement membrane, in the hair follicles and sebaceous glands In intestinal mucosa the stem cells are near the bottom of the crypts In the liver they are found lying between hepatocytes and bile ducts There is also a separate pool of stem cells available in the bone marrow; these haemopoietic stem cells are able to seed into other organs and differentiate locally into the appropriate tissue
64
Process of complete restitution in a 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
65
What is organisation
The repair of specialised tissues by the formation of a fibrous scar. It occurs by the production of granulation tissue and the removal of dead tissue by phagocytosis.
66
What is granulation tissue
Loops of capillaries supported by myofibroblasts which actively contracts to reduce wound size; this may result in a structure later.
67
How can we treat inflammation
NSAIDS, antibiotics, antifungal, aspirin etc
68
Healing by 1st intention
1st detention – can suture up the cut Incision -> exudation of fibrinogen -> weak fibrin join -> epidermal regrowth and collagen synthesis -> strong collagen join
69
Healing by 2nd intention
Can’t bring the skin edges together the cut is too deep Loss of tissue -> granulation tissue -> organisation -> early fibrous scar -> scar contraction Phagocytosis to remove any debris Granulation tissue to fill in defects and repair specialised tissues lost Epithelial regeneration to cover the surface
70
What is repair
Initiating factor still present Tissue damaged and unable to regenerate Replacement of damaged tissue by fibrous tissue Collagen produced by fibroblasts
71
Cells that can regenerate
Hepatocytes Pneumocytes All blood cells Gut epithelium Skin epithelium Osteocytes – help remodel bone fractures
72
Cells that cannot regenerate
Myocardial cells Neurones
73
Why is brain fibrosis called gliosis?
Glial cells instead of fibroblasts
74
What is thrombosis
Solid mass of blood constituents formed within intact vascular system during life
74
What is thrombosis
Solid mass of blood constituents formed within intact vascular system during life
75
What is thrombosis
Solid mass of blood constituents within an intact vascular system during life
76
What is a blood clot
Blood coagulated outside of the vascular system or after death
77
What prevents a thrombus normally
Laminar flow - cells travel in centre of arterial vessels and don't touch sides Endothelial cells - are not "sticky" when healthy
78
Origin and role of platelets
No nucleus and derived from megakaryocytes Platelets are activated and the contents of their granules released when come into contact with collagen, found in damaged vessel walls The platelets change shape and extend pseudopodia; their granules releases their contents and platelets form a mass that covers the vessel wall defect until the endothelial cells have regenerated
79
What do platelets contain
Alpha granules: * Contain several substances involved in the process of platelet adhesion to damaged vessel walls * Substances include; fibrinogen, fibronectin & platelet growth factor Dense granules: * Contain substances such as; adenosine diphosphate (ADP) that cause platelets to aggregate
80
Process of thrombus formation
Platelet aggregation - Platelets release chemicals when the aggregate which cause other platelets to stick to them and also which start off the cascade of clotting proteins in the blood Both these reactions involve positive feedback loops so that once they have started they are difficult to stop Once the clotting cascade has started there is formation of the large protein molecule fibrin which makes a mesh in which red blood cells can become entrapped
81
Three factors that can cause thrombosis
Change in vessel wall Change in blood flow Change in blood constituents Not all 3 are needed.
82
How do cigarette smokers cause the risk factor for thrombosis
cigarette smoke damages endothelial cells resulting in both a change in vessel wall and blood flow over the injured/absent cells
83
Arterial thrombosis process
1. Raised fatty streak on intimal surface 2. Plaque grows to protrude into lumen and turbulent blood flow 3. Turbulance results in loss of intimal cells and exposed plaque is presented to blood cells. 4. Results in fibrin deposits and platelet clumping and platelets adhere to exposed collagen 5. Platelet0growth factor in alpha granules causes proliferation of arterial smooth muscle cells which add to plaque. 6. Platelet layer and rbc become trapped in fibrin meshwork 7. Build up protrudes even further into lumen more platelet deposition 8. disrupts laminar flow and thrombi grow in direction of blood flow (propagation)
84
Venous thrombosis process
Atheroma do not occur due to low bp but starts at valves 1. valves disturb blood flow as protrude into vessel lumen especially if damaged by trauma, stasis or occlusion 2. if bp falls flow is slower (stasis) and thrombosis more likely through successive deposition via propagation
85
Risk factors for venous thrombosis
surgery when bp falls After MI elderly or those immobilised for long periods of time for DVT any individual can get DVT
86
What does arterial thrombosis result in
- The loss of pulse distal to the thrombus - Area becomes cold, pale & painful - Eventually the tissue will die and gangrene results
87
What does venous thrombosis result in
The area becoming tender due to developing ischaemia in the vein wall initially, but there is also general ischaemic pain as the circulation worsens - Area becoming reddened - since blood is still carried to the site by the arteries but cannot be drained away by the veins) - Area becoming swollen
88
Outcomes of thrombi (4)
A - Resolves as body dissolves it B - Organised into a scar by invasion of macrophages which clear away thrombus and fibroblasts replace it with collagen C - intimal cells proliferate and small sprouts of capillaries grow into thrombus and fuse to larger vessels. Recanalised D - Fragments of thrombus may break off resulting in embolism
89
What does aspirin do to a thrombus
inhibits platelet aggregation and a low dose can help prevent it.
90
What does warfarin do
Inhibits vitamin K to prevent clotting
91
What is an embolus
An embolus is a mass of material in the vascular system able to lodge in a vessel and block its lumen
92
Causes of embolus
1. thrombus 2. air 3. Cholesterol crystals 4. Tumour amniotic fluid 5. Fat
93
What happens during a venous embolism
If an embolus enters the venous system it will travel to the vena cava, through the right side of the heart and will lodge somewhere in the pulmonary arteries (depending on its size) - resulting in a PULMONARY EMBOLISM
94
What happens during an arterial embolism
If an embolus enters the arterial system it can travel anywhere downstream of its entry point, for example: - A mural thrombus overlying a myocardial infarct in the left ventricle can go anywhere in the systemic circulation - Cholesterol crystals from an atheromatous plaque in the descending aorta can go to any of the lower limb and renal arteries
95
Effects of a small pulmonary emboli
May occur unnoticed and be lysed within the lung * May become organised and cause some permanent, though small, respiratory deficiency - the accumulation of such damage over a long period may be the cause of so-called ‘idiopathic pulmonary hypertension’
96
Effects of a medium size pulmonary emboli
May be large enough to result in acute respiratory and cardiac problems that may resolve slowly with or without treatment * The main symptoms are; chest pain and shortness of breath due to the effective loss of the area of lung supplied by the occluded vessel - the area may even become infarcted * Although many patients recover, their lung function is impaired and are at risk of further emboli in the future from the same source
97
Effects of a large pulmonary emboli
These result in sudden death * They are usually long thrombi derived from the leg veins and are often impacted across the bifurcation of one of the major pulmonary arteries
98
How does thrombosis occur after AF
ineffectual movement of the atria cause blood to stagnate in the atrial appendages and thrombosis to occur - when the normal heart rhythm is re-established the atrial thrombus may be fragmented and emboli broken off
99
What is ischaemia
A reduction in blood flow to a tissue or part of the body caused by constriction or blockage of the blood vessels supplying it
100
What is infarction
The necrosis / death of part or the whole of an organ that occurs when the artery supplying it has been obstructed
101
Why are people susceptible to infarction
Most of the organs in the human body have only a single artery supplying them (end arterial supply) so they are very susceptible to infarction if this supply is interrupted
102
Organs with dual arterial supply
Liver Lung Brain
103
What is reperfusion injury
Damage when perfusion is resetablished as damage is oxygen dependent and the only way for oxygen to get to the site is by blood flow When blood flow returns to an area of tissue that has been ischaemic, tissue where transport mechanisms across the cell membrane have been disrupted in particular where calcium transport out of the cell and from organelles such as mitochondria is impaired * This appears to be the trigger for the activation of oxygen-dependent free radical systems that begin the clearing away of dead cells - a hallmark of reperfusion injury * Neutrophil polymorphs and macrophages enter the area and begin to clear away debris and themselves import their own intrinsic oxygen free radicals into the area - resulting in more damage
104
What is gangrene
When whole areas of a limb or a region of the gut have their arterial supply cut off and large areas of mixed tissue die in bulk.
105
Two types of gangrene and their features
Dry gangrene: * The tissue dies and become mummified and healing occurs above it * So that eventually the dead area drops off - this is a sterile process, and is the common fate of gangrenous toes as a complication of diabetes - Wet gangrene: * Bacterial infection supervenes as a secondary complication; in this case the gangrene spreads proximally and the patient dies from overwhelming sepsis
106
How does frostbite result in ischaemia
capillaries are damaged in exposed areas and thus construct severely so that the area they normally supply becomes ischaemic and infarcts
107
Alternate causes of infarction
Spasm - decrease NO External compression Steal - diverted blood Hyperviscosity - increased blood viscosity Vasculitis - inflammation of vessel wall
108
What is an atheroma
The fatty material which forms deposits in the arteries.
109
What is an atheroma
The fatty material which forms deposits in the arteries.
110
What is athersclerosis
Disease characterised by the formation of atherosclerotic plaques in the intima and degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and a risk of thrombosis.
111
Complications of atherosclerosis
Cerebral infarction - Carotid atheroma - emboli causing transient ischaemic attacks or cerebral infarcts - Myocardial infarction - Aortic aneurysm - rupture causes certain death - Peripheral vascular disease - Gangrene
112
Characteristics of the plaque composition
- central lipid core with fibrous tissue - Collagens and SMC Macrophages and lymphocytes and mast cells - Bordered by foam cells (macrophages that have phagocytksed oxidised lipoproteins with large amounts of cytoplasm) Calcifications in late stages
113
Risk factors of atherosclerosis
Hypercholersterolaemia Smoking Hypertension Diabetes Male gender Increasing age
114
How do plaques develop
1. Injured endothelial cells: * Enhanced expression of cell adhesion molecules for monocytes * High permeability for macromolecules such as low-density lipoprotein (LDL) * Increased thrombogenicity 2. This allows inflammatory cells and lipids to enter the intimal layer and form plaques 3. In more advanced stages of plaque formation large amounts of macrophages and T cells also accumulate in the plaque tissue 4. Lipid-laden macrophages (foam cells) die, after phagocytosing LDL but eventually die 5. Growth factors, particularly platelet-derived growth factor (PDGF), stimulate the proliferation of intimal smooth muscle cells and the subsequent synthesis of collagen, elastin and mucopolysaccharide by smooth muscle cells 7. This results in the formation of a fibrous cap which encloses the lipid-rich core 8. Growth factors are secreted by; platelets, injured endothelium, macrophages & smooth muscle cells themselves 9. Another important mechanism of plaque growth is haemorrhage - this results from rupture/leakage of micro vessels within the plaque, especially fully developed plaques 10. Large haemorrhage can cause rapid expansion of plaques and may produce clinical symptoms
115
Clinical manifestations of atherosclerosis
1. Progressive lumen narrowing due to plaque stenosis. When the stenosis is severe, ischaemic pain may develop even at rest 2. Acute atherothrombotic occlusion leading to infarction 3. Embolisation 4. Ruptured abdominal atherosclerotic aneurysm leading to haemorrhage
116
Preventative measures of atherosclerosis
- Smoking cessation - Control of blood pressure - Weigh reduction - Low dose aspirin - inhibits the aggregation of platelets, advised for people with clinical evidence of atheromatous disease - Statins - cholesterol reducing drug
117
What is an aneurysm
A localised permanent dilation of part of the vascular tree
118
What is an atherosclerotic aneurysm
Commonly develop in elderly patients - They may impair blood flow to the lower limbs and contribute to the development of peripheral vascular disease - They may rupture into the retroperitoneal space
119
What Is an aortic dissection aneurysm
Blood is forced through a tear in the aortic intima to create a blood-filled space in the aortic media - This can track back into the pericardial cavity, causing a fatal haemopericardium (blood in pericardiac sac), or can rupture through the aortic adventitia
120
What is a berry aneurysm
Occur in the circle of willis, the normal muscular arterial wall is replaced by fibrous tissue - The lesions arise at points of branching, and are more common in young hypertensive patients - Results in a subarachnoid haemorrhage if ruptured
121
What is a stroke
A sudden event with disturbance of CNS functions due to vascular disease
122
Types of stroke
Transient Ischaemic attack Cerebral infarction Intracranial haemorrhage Subarachnoid haemorrhage
123
What is a TIA
A stroke that lasts for less than 24hours and that is associated with complete clinical recovery - Although they show complete resolution, they are risk markers for subsequent cerebral infarction
124
What is a Cerebral infarction and its causes
Most occur within the internal carotid territory, particularly in the distribution of the middle cerebral artery Thrombosis Emboli Head injury Occlusion Reduction in blood flow, oxygen or infection
125
What is an intracranial haemorrhage and where does it occur
Occurs 80% of the time in the basal ganglia Other places include; brainstem, cerebellum and cerebral cortex * Most occur in hypertensive adults over 50 * The haemotoma that forms as a result of the haemorrhage acts as a space-occupying lesion resulting in a rapid increase in intracranial pressure & herniation * Most intracerebral haemorrhage occur following the rupture of the lenticulostriate branch of the MIDDLE CEREBRAL ARTERY
126
What is a sub arachnoid haemorrhage and its causes
Occurs between the arachnoid and pia layers of the cranial meninges - haemorrhage here results in an increase in pressure between the layers which in turn puts pressure on the underlying brain and intracranial vessels * Occurs usually due to the spontaneous rupture of a saccular aneurysm on the circle of willis
127
What is apoptosis
A physiological cellular process in which a defined and programmed sequence of intracellular events leads to the removal of a cell WITHOUT the release of products harmful to surrounding cells (programmed cell death)
128
What is necrosis
traumatic cell death which induces inflammation and repair
129
Purpose of apoptosis
ensures a continuous renewal of cells - enabling tissues to be more adaptable to environmental demands act to suppress the inflammatory response triggered by necrosis
130
How is HIV defective apoptosis
HIV proteins may activate CD4 on uninfected T-helper lymphocytes inducing apoptosis with resulting immunodepletion & dysfunction
131
Apoptosis inhibitors
- Growth factors - Extracellular cell matrix - Sex steroids - Some viral proteins
132
Apoptosis inducers
- Growth factor withdrawal - Loss of matrix attachment - Glucocorticoids - Some viruses - Free radicals - Ionising radiation - DNA damage - Ligand-binding at ‘death receptors’
133
Intrinsic pathways of apoptosis
Bcl-2 can inhibit many factors that induce apoptosis Bax forms Bax-Bax dimers which enhance apoptotic stimuli intrinsic pathway responds to stimuli such as growth factors (or their withdrawal) and biochemical stress
134
How is the p53 involved in apoptosis?
p53 is a multifunctional protein which induces cell cycle arrest and initiates DNA damage repair When DNA damage occurs this leads to the stabilisation of the protein product of the p53 gene However if the damage is more difficult to repair then p53 can induce APOPTOSIS via activation of pro-apoptotic members of the Bcl-2 family
135
Extrinsic pathway of apoptosis
Activation of apoptosis characterised by ligand-binding at death receptors on the cell surface tumour necrosis factor receptor (TNFR) gene family e.g.: * TNFR1 * Fas (CD95) Ligand binding at these receptors promotes clustering of receptor molecules on the cell surface, and the initiation of a signal transduction cascade resulting in the activation of CASPASES (cell death enzymes) - This pathway is the mechanism by which the immune system eliminates lymphocytes that would otherwise produce self-antigens
136
Execution phase of apoptosis
Activation of apoptosis by either the intrinsic or extrinsic pathways results in a cascade of activation of caspases - Caspases are proteases, normally present as inactive pro-caspase molecules - Triggering of apoptosis first leads to the activation of initiator caspases to produce active caspases which cause the degradation of many targets including the cytoskeletal framework and nuclear proteins - Dead cells not phagocytosed fragment into smaller membrane-bound apoptotic bodies - these bodies do not trigger an inflammatory response and are eventually phagocytosed
137
What is coagulative necrosis
Commonest form of necrosis * Can occur in most organs * Caused by ischaemia * Following the lack of blood, the cells will retain their outline as their proteins coagulate and metabolic activity ceases
138
What is liquefactive / colliquative necrosis
Occurs in the brain because of its lack of any substantial supporting stroma; thus necrotic neural tissue may totally liquefy
139
What is caseous necrosis
a pattern of necrosis in which the dead tissue is structureless almost like “soft cheese” * Whenever caseous necrosis is seen in biopsy TUBERCULOSIS MUST be thought of
140
What is gangrene necrosis
Type of necrosis with rotting of the tissues, sometimes as a result of certain bacteria particularly clostridia * The affected tissue appears black because of the deposition of iron sulphide from degraded haemoglobin