Intro To Clinical Sciences Flashcards
1
Q
What are the 2 types of autopsy?
A
- Hospital Autopsy
2. Medico-legal autopsies
2
Q
Describe what a Hospital Autopsy entails…
A
- Account for less than 10% of UK autopsies
- Requires a medical certificate of cause of death
- Used for teaching research & governance
3
Q
Describe what a Medico-legal Autopsy entails…
A
- Account for more than 90% of UK autopsies
- Coronial Autopsies: where death is not due to unlawful action
- Forensic autopsies: where death is thought unlawful, e.g. murder
4
Q
What 4 questions does the Coronial autopsy answer?
A
- Who was the deceased?
- When did they die?
- Where did they die?
- How did their death come about?
(essentially performs the same role as the coroner)
5
Q
What deaths will be refereed to the coroner?
A
- Presumed Natural
- Presumed iatrogenic
- Presumed unnatural
6
Q
What does a Presumed Natural death entail?
A
- Cause of death unknown
- Patient hasn’t seen doctor within 14 days prior to death
- Most common reason for referral
7
Q
What does a Presumed Iatrogenic death entail?
A
- Peri/postoperative deaths
- Anaesthetic deaths
- Illegal abortions
- Complications or therapy (even if recognised complication)
8
Q
What does a Presumed Unnatural death entail?
A
- Accidents
- Industrial death
- Suicide
- Unlawful killing i.e. murder
- Neglect
- Custody death
9
Q
Who can refer for a coronial autopsy?
A
Doctors:
- do NOT have statutory duty to refer
- common law duty
- guidance provided by GMC
Registrar of BDM:
- Statutory duty to refer
Others:
Police
Relatives
10
Q
What autopsies do Histopathologists perform?
A
Hospital autopsies Coronial autopsies: - Natural deaths - Drowning - Suicide - Accidents - Road traffic deaths - Fire deaths - Industrial deaths - Peri/postoperative death
11
Q
What autopsies do Forensic pathologists perform?
A
Coronial Autopsies:
- Homicide
- Death in custody
- Neglect
- Any from the coronial list of the histopathologist that may be due to the action of a third party
12
Q
What are the 5 different steps of an autopsy?
A
- History/ Scene
- External Examination
- Evisceration
- Internal examination
- Reconstruction
13
Q
What examinations/processes does an autopsy entail?
A
- Microbiology
- Toxicology
- Radiology
- Genetics
- Histology
- Digital photography
14
Q
What is looked for at the step of external examination?
A
- Identification:
Formal identifiers, gender, age, body habitus (build), jewellery, body modification, clothing - Disease & treatment
- Injuries
15
Q
What happens within the evisceration stage?
A
- Y-shaped cut; from behind the ears down to clavicles then down to mid-line
- Open all body cavities
- Examine all organs in situ
- Remove thoracic and abdominal organs
- Remove brain
16
Q
What does the internal examination stage entail?
A
- Heart & great vessels
- Lungs, trachea & bronchi
- Liver, gallbladder, pancreas
(avoid lower GI tract to prevent infection risk) - Spleen, thymus, lymph nodes
- Genitourinary tract (common site of cancer)
- Endocrine organs
- Central nervous system
17
Q
What is the definition of Acute Inflammation?
A
The initial and often transient series of tissue reactions to injury - may last from a few hours to a few days.
18
Q
Give an example of acute inflammation
A
Appendicitis
19
Q
What is inflammation?
A
- The local physiological response to tissue injury
- Nota disease itself, but instead usually a manifestation of disease
20
Q
What are the benefits of inflammation?
A
Destruction of invading microorganisms and the walling off of an abscess cavity, thereby preventing the spread of an infection.
21
Q
What are the limitations of inflammation?
A
- Disease; e.e.g abscess in the brain can act as a space-occupying lesion that can compress surrounding structures
- Fibrosis resulting from chronic inflammation may distort tissues and permanently alter their function
22
Q
Describe the steps of cute inflammation
A
- Initial reaction of tissue to injury.
- Vascular component dilation of vessels
- Exudative component: vascular leakage of protein-rich fluid
- Neutrophil polymorph is recruited to the tissue.
23
Q
What are the possible outcomes of acute inflammation?
A
- Resolution; goes away
- Suppuration; pus formation e.g. abscess
- Organisation
- progression to Chronic inflammation
24
Q
Explain in detail the Organisation outcome of acute inflammation…
A
- This is healing by fibrosis (scar formation)
- substantial damage to connective tissue framework and the tissue lacks the ability to regenerate specialised cells
- Macrophages remove dead tissue and acute inflammatory exudate from the damaged areas
- The defect then becomes infilled by the growth of a specialised vascular connective tissue (granulation tissue)
- the granulation tissue gradually produces collagen to form a fibrous (collagenous) scar constituting the process of repair
25
What are the causes of acute inflammation?
- Microbial infections: pyogenic bacteria, viruses
- Hypersensitivity reactions: parasites, tubercle bacilli
- Physical agents: trauma, ionising radiation, heat, cold (frost-bite)
- Chemicals: corrosives, acids, alkalis, reducing agents
- Bacterial toxins
- Tissue necrosis: ischaemic infarction
26
Explain Microbial infections as a cause of acute inflammation
- One of the most common causes
- Viruses lead to death of individual cells by intracellular multiplication
- Bacteria release specific exotoxins (chemicals synthesised by them to initiate inflammations)
or can release specific endotoxins (associated with their cell walls)
- some organisms can cause hypersensitivity reactions via immunologically mediated inflammation
- Parasitic infections & tuberculous inflammation = hypersensitivity is VITAL
27
Explain hypersensitivity reactions as a cause of acute inflammation
- Occur when an altered state of immunological responsiveness causes an inappropriate or excessive immune reaction that damages tissues
- Involve cellular or chemical mediators (similar to those involved in inflammation)
28
Explain physical agents as a cause of acute inflammation
- Physical trauma, ultravoilet or other ionising radiation, burns or excessive cooling may cause tissue damage that leads to inflammation
29
Explain irritant & corrosive chemicals as a cause of acute inflammation
- Corrosive chemicals provoke inflammation through gross tissue damage
- Infecting agents can release specific irritants that lead directly to inflammation
30
Explain tissue necrosis as a cause of acute inflammation
- Death of tissues due to lack of oxygen/ nutrients as a result of infarction is a potent inflammatory stimulus
- The edge of a recent infarction often shows an acute inflammatory response due to the peptides released from dead tissue
31
What are the 4 essential macroscopic appearances of acute inflammation?
(and 1 that is also characteristic)
1. Redness; Rubor
2. Heat; Calor
3. Swelling; tumour
4 Pain; Dolor
- Loss of function is also characteristic
32
AI; what causes redness (rubor)?
- Acutely inflamed tissue appears red due to the dilation of small blood vessels within the damaged area
33
AI: what causes heat (dolor)?
- only seen in the peripheral parts of the body i.e. skin
- due to increased blood flow (hyperaemia) through the region, resulting in vascular dilation
- increase in temp can also be caused by systemic fever resulting from chemical mediators of inflammation
34
AI: what causes swelling (tumour)?
- due to accumulation of fluid in the extravascular space as part of the fluid exudate - oedema
- very slightly due to the mass of inflammatory cells migrating into the damaged area
- formation of new connective tissue also contributes to the swelling (once the inflammation response has started to progress)
35
AI: what causes pain (dolor)?
- due to the stretching and distortion of tissues due to inflammatory oedema and pus under pressure in an abscess cavity
36
AI: what causes loss of function?
- movement of an inflamed area is consciously and reflexly inhibited by pain
- severe swelling my physically immobilise the tissues too
37
What happens in the early stages of acute inflammation?
- Oedema fluid, fibrin and neutrophil polymorphs accumulate in the extracellular space of the damaged tissue
- Cellular component presence of neutrophil polymorphs is essential for the histological diagnosis of acute inflammation
38
What are the 3 steps of the acute inflammatory response process?
1. Changes in vessel calibre (gets wider) and consequently increased vessel flow
2. Increased vascular permeability and formation of the fluid exudate
3. Formation of the cellular exudate - emigration of the neutrophil polymorphs into the extravascular space
39
Explain the vascular changes that occur in acute inflammation:
- Precapillary sphincters in arteriolar walls relax, so increase blood flow through capillaries; contributing to redness and heath
- Capillary hydrostatic pressure is increased and there is escape of plasma proteins into the extravascular space (due to increased pressure), so osmotic pressure is increased - resulting in more fluid leaving the vessels than returning into them = increased vascular permeability
40
What is the net escape of protein-rich fluid called?
Exudation; Fluid exudate
41
What are the causes of increased vascular permeability?
- Immediate transient; Chemical mediators ie. histamine, bradykinin (vasodilators), complements,, platelet activating factor
- Immediate sustained; severe direct vascular injury
- Delayed prolonged; endothelial cell injury
42
What is the diagnostic histological feature of acute inflammation?
The accumulation of neutrophil polymorphs with the extracellular space.
43
What are the stages of neutrophil polymorph emigration?
1. Margination of neutrophils
- loss of intravascular fluid and increase in plasma viscosity with slowing of flow at the site of AI means neutrophils can flow into the plasmatic zone
2. Adhesion of neutrophils
- attach to the vascular endothelium at the site of AI --> 'pavementing'
- at site of injury pavementing occurs early in the AI response (only in VENULES)
- interaction between paired adhesion molecules on leucocyte & endothelial surfaces results in increased leucocyte adhesion
3. Neutrophil emigration
- leucocytes migrate through walls of venules and small veins (not commonly exit from capillaries)
- neutrophils, eosinophil polymorphs & macrophages insert pseudopodia between endothelial cells
- allows migration through the gaps between endothelial cells through basal lamina into the vessel wall
4. Diapedesis
- RBCs also escape from vessels, the process is passive, depends on hydrostatic pressure forcing cells out
- large numbers of RBCs in extracellular space = severe vascular injury
44
What allows the spread of AI from the site of damage?
Due to the release of chemical substances from the injured tissues spreading outwards into surrounding uninjured areas.
45
What chemical mediators are released early in the response? and by what? and what do they cause?
Histamine and Thrombin.
Released by the original inflammatory stimulus.
Cause the up-regulation of adhesion molecules on the surface of endothelial cells.
46
What is the overall effect of chemical mediators of acute inflammation?
Very firm neutrophil adhesion to the endothelial surface
47
What do the endogenous chemical mediators cause?
- Vasodilation
- Emigration of neutrophils
- Chemotaxis (attraction of neutrophil polymorphs towards certain chemicals)
- Increased vascular permeablity
- Itching and pain
48
Histamine release in AI, effects, source, stimulated by...
Causes:
- vascular dilation
- immediate transient phase of increased vascular permeability
- has an immediate effect due to storage in preformed granules = instant release
Sources:
- Mast cells
- Basophil and eosinophil leucocytes
- Platelets
Stimulated by:
- Complement components C3a & C5a
- Lysosomal proteins released from neutrophils
49
What other chemical mediators are there?
- Lysosomal compounds
- Eicosanoids (prostoglandins)
- 5-hydroxytryptamine (serotonin)
- Chemokine (chemotactic cytokines)
50
What are the 4 enzymatic cascade systems that plasma contains?
1. Complement
2. The Kinins
3. Coagulation factors
4. Fibrinolytic system
All interrelated and produce various inflammatory mediators.
51
What is the complement system?
A complex series of interacting plasma proteins. They form a major effector system for antibody-mediated immune reactions.
Remove/ destroy antigens either by direct lysis or by opsonisation.
52
What is opsonisation?
The enhancement of phagocytosis by factors (opsonins) in various ways.
53
How is the complement system activate during the AI reaction?
Tissue necrosis; enzyme that activates complement are released from dying cells
Infection; formation of antigen-antibody complexes activate complement via the classical pathway.
Endotoxins of gram-negative bacteria activate complement via the alternative pathway.
54
Describe the effect of Coagulation factor XII (Hageman factor) on the different enzymatic cascade systems.
```
(See flow chart)
Activates...
- Kinin system
- Fibrinolytic system
- Coagulation system
```
55
Describe the Kinin system
Activated factor XII and plasmin activate the conversion of prekallikrein to kallikrein.
This in turn stimulates the conversion of kininogens to kinins (ie. bradykinin - causes vasodilation).
Prekallikrein can also be activated by leucocyte proteases.
(see flow chart for more detail).
56
Describe the role of tissue macrophages in AI
- Secrete numerous chemical mediators when stimulated (local infection/injury)
- Interleukin-1 and tumour necrosis factor alpha; their stimulatory effects on endothelial cells occur after histamine and thrombin, cause endothelial cells, fibroblasts and epithelial cells to secrete MCP-1
- MCP-1 = powerful chemotactic protein that attracts neutrophil polymorphs
- Blood monocytes go to site of AI, on leaving the blood vessels transform into macrophages
- Phagocytosis of microorganisms is enhanced by opsonisation by antibodies or by complement
- macrophages appear within a few hours after inflammation, do not predominate until neutrophils have diminished and macrophage population has enlarged by local proliferation
- macrophages; clear away tissue debris and damaged cells
- macrophages and neutrophils may discharge lysosomal enzymes into the extracellular fluid (aids digestion of inflammatory exudate)
57
Describe terminal and collecting lymphatics
Terminal lymphatics;
- blind-ended, endothelium lined tubed present in most tissues
- drain in collecting lymphatics
Collecting lymphatics;
- have valves , so propel lymph passively aided by contraction of neighbouring muscles (to the lymph nodes)
58
What is the role of lymphatics in acute inflammation?
- lymphatic channels become dilated in AI as they drain away the oedema fluid of the inflammatory exudate
- drainage tends to limit the extent of oedema in the tissues
- antigens are carried to the regional lymph node for recognition by lymphocytes
- vital part of the immune response
59
What is a neutrophil polymorph?
- the most common white blood cell
- under H&E stain, nucleus stains blue and cytoplasm stains pink/purple
- characteristic cell of acute inflammatory infiltrate
60
Role of neutrophil polymorph in AI?
- Neutrophil polymorph ingests the antigen
- The antigen lies within a phagocytic vacuole (phagosome)
- Lysosomes then fuse with the phagocytic vacuole and enzymes digest the antigen (phagolysosome)
- Antigen debris released from neutrophil polymorph and lysosomes are replenished
61
How does adhesion to microorganisms occur?
- Microorganisms are opsonised; rendered more amenable to phagocytosis either by immunoglobulins or by complement components
- bacterial lipopolysaccharides activate complement via the alternative pathway, via the alternative pathway, generating component C3b (opsonising properties)
- antibody binding to bacterial antigens activates complement via the classical pathway (generating C3b)
- binding of immunoglobulins to microorganisms by their Fab components leaves the Fc component exposed - neutrophils have surface receptors for the Fc fragment of immunoglobulins and consequently bind to the microorganisms prior to ingestion
62
Describe the process of phagocytosis
- Implemented by neutrophil polymorphs and macrophages
- first step = adhesion of particle to be phagocytosed to the cell surface (opsonisation)
- phagocyte ingests the attached particle by sending out pseudopodia around it; they meet and fuse so particle is within a phagosome bound by ecll membrane
- lysosomes fuse with the phagosome to form pahgolysosomes - within this intracellular killing takes place
63
Describe the process of intracellular killing of microorganisms
Noxious microbicidal agents within neutrophil polymorphs are used. These are:
1. Oxygen-dependent; Hydrogen peroxide reacts with myeloperoxidase in cytoplasmic granules of the neutrophil polymorph in the presence of a halide - produces a potent microbicidal agent
2. Oxygen-independent; lysozyme (muramidase) & lactoferrin
64
what are the effects of release of lysosomal products?
- Damage local tissues by proteolysis via enzymes (elastase and collagenase)
- Activate coagulation factor XII
- Attract other leukocytes to the area
- Some compounds increase vascular permeability,
- Others are pyrogens; induce systemic fever by acting on hypothalamus
- life span of 1 to 3 days
65
Role of mast cells in AI
- Are stimulated by C3/ C5a complement components
- Release preformed inflammatory mediators stored in their granules
- Metabolise arachidonic acid into newly synthesised inflammatory mediators (i.e. leukotrienes, prostaglandins, thromboxanes)
66
What are the special macroscopic appearances of AI?
Cardinal signs are modified according to the type of tissue involved and what type of agent is provoking the inflammation.
- Serous inflammation
- Suppurative inflammation (lots of pus)
- Membranous inflammation
- Pseudomembranous inflammation
- Necrotising (gangrenous) inflammation
67
What are the effect of AI?
Both local and systemic effects, that can both be beneficial or harmful.
68
What are the beneficial effects of the fluid exudate?
- Dilution of toxins; can then be carried away via lymphatics
- Entry of antibodies due to increased vascular permeability into the extravascular space
- transport of drugs to specific site
- Fibrin formation from exuded fibrinogen; can impede microorganism movement
- Delivery of nutrients and oxygen
- Stimulation of immune response via drainage of fluid exudate into the lymphatics
69
What are the harmful effects of AI?
- Digestion and destruction of normal tissues; collagensases and proteases
- Swelling; most serious when in enclosed spaces i.e. cranial cavity
- Inappropriate inflammatory response
70
What are the possible outcomes of AI?
Usual result --> Resolution
Excessive exudate --> Suppuration--> discharge of pus
Excessive necrosis --> repair and organisation --> fibrosis
Persistent causal agent --> Chronic inflammation --> fibrosis
71
What is Resolution of AI?
- Complete restoration of the tissues to normal after an episode
- favoured by the following conditions:
- minimal cell death and tissue damage
- occurred in organ capable of regeneration
- rapid destruction of causal agent
- rapid removal of fluid and debris by goo local vascular drainage
example: acute lobar pneumonia
72
What is Suppuration of AI?
- Formation of pus, mixture of living, dying and dead neutrophils/ bacteria/ cellular debris
- causative stimulus fairly persistent, virtually always an infective agent
- pus accumulating in tissue: is surrounded by a 'pyogenic membrane' = sprouting capillaries, neutrophils and occasional fibroblasts = start of healing
- results in granulation tissue and scarring
- bacteria within an abscess are relatively inaccessible to antibodies and to antibiotic drugs
73
What is the resolution of an abscess?
- Usually points then bursts; abscess cavity collapses and is obliterated by organisation and fibrosis - leaves a scar
- sometimes requires surgical drainage to eliminate
- if accumulates inside a hollow organ, mucosal layers of outflow tract of the organ may become fused together by fibrin and result in an empyema
74
What is Organisation of AI?
- the replacement of tissues by granulation tissue as part of the repair process
- new capillaries grow into the inflammatory exudate, macrophages migrate into the area and fibroblasts proliferate (under the influence of TGF-beta) = result in fibrosis and possible scar formation
Favoured by the following conditions:
- large amounts of fibrin, that cannot be removed completely by fibrinolytic enzymes
- substantial volumes of tissue becoming necrotic or if dead tissue is not easily digested
- exudate debris unable to be removed or discharged
example: pleural space following acute lobar pneumonia
75
What is the process of progression to chronic inflammation following AI?
- Causal agent is not removed
- Nature of cellular exudate changes, neutrophil polymorphs are replaced by lymphocytes, plasma cells, macrophages, multinucleate giant cells and fibroblasts
76
What are the systemic effects of inflammation?
- Pyrexia (fever)
- Constitutional symptoms: malaise, anorexia, nausea, weight loss
- Reactive hyperplasia of the reticuloendothelial system
- Haematological changes
- Anaemia
- Amyloidosis
77
What is pyrexia (fever)?
- Endogenous pyrogens are produced by neutrophil polymorphs and macrophages
- these act on the hypothalamus to set the thermoregulatory mechanisms at a higher temp.
- Pyrogen interleukin-2 has the greatest effect
- Release of pyrogens is stimulated by phagocytosis, endotoxins and immune complexes
78
What is reactive hyperplasia of the reticuloendothelial system?
- local or systemic lymph node enlargement commonly accompanies inflammation
- splenomegaly found in specific infections
79
What haematological changes are seen with inflammation?
- Increased levels of white blood cells in the blood: neutrophils - pyogenic infections, eosinophils - allergic disorders and parasitic infection, lymphocytes - chronic infection, whooping cough, many viral infections, monocytes - bacterial infections
- Anaemia due to blood loss into the inflammatory exudate or haemolysis
80
What is amyloidosis?
- Caused by long-standing chronic inflammation, by elevating serum amyloid A protein (SAA)
- Causes amyloid to be deposited in various tissues
- Can lead to secondary (reactive) amyloidosis
