Session 2 Flashcards
1
Q
What is acute inflammation?
A
The response of living tissue to injury; protective mechanism.
2
Q
What are the main features of acute inflammation?
A
- Innate
- Always the same regardless of stimulus
- Short duration
- Immediate
3
Q
What causes inflammation?
A
- Microorganisms
- Foreign bodies
- Hypersensitivity
- Necrosis
4
Q
What are clinical signs of acute inflammation?
A
- Tumor = swelling
- Rubor = redness
- Calor = heat
- Dolor = pain
- Loss of function
5
Q
What are the changes in the vascular phase?
A
- Transient vasoconstriction (seconds)
- Vasodilatation (causes heat and redness - more blood flow)
- Increased permeability that allows fluid and cells to escape
6
Q
What is movement of fluid controlled by?
A
Starling’s law.
- Hydrostatic pressure: pressure exerted on vessel wall by fluid (pushes fluid out)
- Oncotic pressure: pressure exerted by proteins that draws fluid in
Both exist in the vessels and interstitium and when balance, there is no water flow.
7
Q
How do pressures change in acute inflammation?
A
- Vasodilatation causes increased HYDROSTATIC pressure
- Increased vessel permeability allows plasma proteins to move into interstitium and increase INTERSTITIAL ONCOTIC PRESSURE
8
Q
What do pressure changes cause?
A
Oedema/tumor
9
Q
What is a result of fluid moving out of vessel?
A
Increased blood viscosity - blood is thicker and not as diluted by fluid and therefore causes STASIS (reduced flow through vessel)
10
Q
What type of interstitial fluid is exudate?
A
- Increased vascular permeability
- Protein rich fluid to deliver proteins into area of trauma
= INFLAMMATION
11
Q
What type of interstitial fluid is transudate?
A
Unchanged vascular permeability. Fluid moves due to either:
- Reduced capillary oncotic pressure
- Increased capillary hydrostatic pressure
12
Q
When does transudate occur?
A
- Heart failure (blood pooling causes increased capillary hydrostatic pressure)
- Liver failure (less protein synthesis = reduced capillary oncotic pressure)
- Renal failure
13
Q
How does a vessel become permeable and how is it controlled?
A
Retraction of endothelial cells that creates gaps.
- Controlled by CHEMICAL MEDIATORS:
- Leukotrienes, Histamine, Nitric oxide - DIRECT INJURY
- Burns, trauma, toxins - allows proteins and cells to escape - LEUCOCYTE DEPENDENT INJURY
- Reactive oxygen species released by activated neutrophils
14
Q
How is the vascular phase effective?
A
- Interstitial fluid dilutes toxin
- Exudate delivers proteins that limit spread of toxin (fibrin)
- Exudate delivers immunoglobulins as part of adaptive immune response to destroy the toxin
15
Q
Where does interstitial fluid drain and why?
A
- Drains into lymph nodes
- Delivers antigens to stimulate the adaptive immune response
16
Q
What is the cellular phase of inflammation controlled by?
A
The neutrophil.
Enter tissues - trilobed nuclei stain purple
17
Q
How do neutrophils escape vessels?
A
- MARGINATION: Increased viscosity causes neutrophil to stick to the edge of the vessel
- ROLLING: weak intermittent bond with the vessel
- ADHESION: binding tighter to the edge of vessel
- EMIGRATION/DIAPEDESIS: neutrophils changes conformation to squeeze through endothelial cells
18
Q
What adhesion molecules help with neutrophil vessel escape?
A
- Selectins: on endothelial cells activated by chemical mediators
Responsible for rolling (weak binding) - Integrins: on neutrophil surface, change from low to high affinity state
Responsible for adhesion (tight binding)
19
Q
How do neutrophils move through interstitium?
A
Chemotaxis - along an increasing chemical gradient of chemoattractants (e.g. bacterial peptides and inflammation mediators)
20
Q
What is the function of neutrophils?
A
Phagocytosis (cover in MEH, revisit) and release of inflammatory mediators. Also releases debris from phagocytosis to dissolve in blood via exocytosis.
21
Q
How do neutrophils recognise what to phagocytose?
A
- Opsonisation
- Pathogen gets covered by FC and C3b opsonins
- Receptors found on neutrophil surface = binds to introduce neutrophil to pathogen
22
Q
What are neutrophil oxygen-dependent killing mechanisms?
A
- Reactive oxygen intermediates (superoxide, hydroxyl radical, hydrogen peroxide)
- Reactive nitrogen intermediates (nitric oxide and dioxide)
23
Q
What are some oxygen-independent killing mechanisms?
A
- Lysozyme
- Hydrolytic enzymes
- Defensins
24
Q
How is the cellular phase effective?
A
- Removal of pathogens and necrotic tissue
- Release of inflammatory mediators
25
What are inflammatory mediators?
Chemical messengers that control and co-ordinate the inflammatory response. Have overlapping functions.
26
What do inflammatory mediators originate from?
- Activated inflammatory cells
- Platelets
- Endothelial cells
- Toxins
27
What mediates vasodilatation?
- Histamine
- Serotonin
- Prostaglandins
- Nitric oxide
28
What mediates vascular permeability?
- Histamine
- Bradykinin
- Leukotrienes
- C3a & C5a
29
What mediates chemotaxis?
- C5a
- Tumour necrosis factor
- IL-1
- Bacterial peptides
30
What mediators are pyrogens?
- Prostaglandins
- IL-1 and IL-6
- TNF-a
31
What inflammatory mediators induce pain?
- Bradykinin
| - Prostaglandins
32
What are local complications of acute inflammation?
Swelling - dangerous if compresses tubes (eg. airways/intestines)
Compression of organs by exudate - eg. cardiac tamponade
Loss of fluid - severe dehydration (burns)
Pain - muscle atrophy and psychosocial consequences
33
What are systemic complications of acute inflammation?
Fever - pyrogens act on hypothalamus to alter temperature
Leucocytosis - increased white cell production as inflammatory mediators act on bone marrow.
Acute phase response - feeling unwell, tachycardia - induces rest
Acute phase proteins - CRP (sensitive not specific)
34
How is fever brought down?
NSAIDs - block cyclo-oxygenase enzymes and therefore production of prostaglandin so that fever is reduced
35
What are the differences between viral and bacterial leucocytosis?
Viral: lymphocytes
Bacterial: neutrophils
36
What is septic shock?
A systemic complication.
- Huge release of chemical mediators that spread throughout body
- Vasodilatation in whole body - lower TPR = tachycardia, hypotension and multi organ failure
- IV AND ANTIBIOTICS IMMEDIATELY!
37
What happens after acute inflammation in complete resolution?
- Mediators degraded/inactivated due to short half-lives.
- Neutrophils apoptose
- Exudate drains via lymphatics to reduce oedema
- If tissue architecture preserved - regeneration
38
What happens after acute inflammation in fibrosis?
- Fibrosis
Repair with connective tissue when a lot of tissue destruction
- Progression to chronic inflammation
Long inflammation with repair; acute not adequate
39
What causes appendicitis?
- Blocked lumen from faecolith
- Accumulation of bacteria and exudate
- Increased pressure can lead to perforation
40
What causes pneumonia?
(Streptococcus pneumoniae
Haemophilus influenzae)
Buildup of exudate in lungs - impairs gas exchange. Causes sputum, fever, shortness of breath. Neutrophils in alveoli.
41
What are risk factors for pneumonia?
- Lung conditions (asthma, COPD)
| - Smoking
42
What causes bacterial meningitis?
(Neisseria meingitides)
Inflammation + exudate in narrow meningeal space
Causes headache, photophobia and altered mental state
43
What are abscesses?
Accumulation of dead neurophils - liquefactive necrosis)
Can compress surrounding structures and cause pain and duct blockages
44
What serous cavities can get inflamed?
- Pleural and pericardial space (effusions)
- Peritoneal space - ascites
Exudate into serous cavities.
45
What is hereditary angio-oedema?
- Inherited deficiency of C1-esterase inhibitor so patients have attacks of itchy oedema and intestinal oedema.
46
What is alpha-1 antitrypsin deficiency?
Condition that allows uninhibited inflammation (especially in lungs) which can cause tissue destruction and fibrosis as AAT usually deactivates enzymes released from neutrophils to protect own tissues.
- Liver disease (protein incorrectly folded, can't be exported = CIRRHOSIS)
47
What is chronic granulomatous disease?
- Phagocytes unable to generate superoxide
- Cannot kill bacteria
- Chronic infections when young
48
What are medicolegal autopsies?
- Performed on behalf of HM Coroner
| - No consent needed
49
What are forensic autopsies?
- Also coroner's post mortems
| - Performed in suspicious deaths (eg. murders, suicides)
50
What are hospital/consent autopsies?
- Need consent from next of kin
51
When are coroner's autopsies performed?
- When doctor can't determine cause of death
- When deceased is unknown
- When death is obviously unnatural
- When death is related to work accident
- When death is related to medical treatment
- Individuals detained by state (prisoners)
52
What is involved in an autopsy?
- History
- External examination: natural disease? injury? imaging?
- Internal examination: all systems examined unless no consent
53
What additional tests have to be done?
- Histology: make/confirm diagnosis
- Toxicology: drugs, blood, urine, bile
- Microbiology: bacteria, viruses, fungi
- DNA fingerprinting: genetic diseases, suspects
- Biochemistry: ketoacidoses, renal failure
54
What are some causes of sudden death (head)?
- Subdural haemorrhage (between dura and arachnoid maters)
- Extradural haemorrhage (between dura mater and skull)
- Subarachnoid haemorrhage (rupture of 'berry' aneurysm)
- Haemorrhagic/ischaemic strokes
55
What are some causes of sudden death (heart)?
- Coronary thrombosis (rupture causes haemopericardium)
- Valvular disease
- Cardiomyopathies
- Aortic aneurysms that rupture
- DVT
56
What are causes of sudden death (lungs + other)?
- Bronchopneumonia
- Pulmonary embolism (DVT)
- Peritonitis
57
What is neuropathology?
Branch of autopsy dealing with trauma, neurodegenerative disease & research
58
What is paediatric pathology?
Child autopsies.
- In-utero & perinatal deaths
- Sudden infant death
- Suspicious deaths
- Medicolegal & safeguarding issues
- Provide answers for families
