Session 2 Flashcards
What is acute inflammation?
The response of living tissue to injury; protective mechanism.
What are the main features of acute inflammation?
- Innate
- Always the same regardless of stimulus
- Short duration
- Immediate
What causes inflammation?
- Microorganisms
- Foreign bodies
- Hypersensitivity
- Necrosis
What are clinical signs of acute inflammation?
- Tumor = swelling
- Rubor = redness
- Calor = heat
- Dolor = pain
- Loss of function
What are the changes in the vascular phase?
- Transient vasoconstriction (seconds)
- Vasodilatation (causes heat and redness - more blood flow)
- Increased permeability that allows fluid and cells to escape
What is movement of fluid controlled by?
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.
How do pressures change in acute inflammation?
- Vasodilatation causes increased HYDROSTATIC pressure
- Increased vessel permeability allows plasma proteins to move into interstitium and increase INTERSTITIAL ONCOTIC PRESSURE
What do pressure changes cause?
Oedema/tumor
What is a result of fluid moving out of vessel?
Increased blood viscosity - blood is thicker and not as diluted by fluid and therefore causes STASIS (reduced flow through vessel)
What type of interstitial fluid is exudate?
- Increased vascular permeability
- Protein rich fluid to deliver proteins into area of trauma
= INFLAMMATION
What type of interstitial fluid is transudate?
Unchanged vascular permeability. Fluid moves due to either:
- Reduced capillary oncotic pressure
- Increased capillary hydrostatic pressure
When does transudate occur?
- Heart failure (blood pooling causes increased capillary hydrostatic pressure)
- Liver failure (less protein synthesis = reduced capillary oncotic pressure)
- Renal failure
How does a vessel become permeable and how is it controlled?
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
How is the vascular phase effective?
- 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
Where does interstitial fluid drain and why?
- Drains into lymph nodes
- Delivers antigens to stimulate the adaptive immune response
What is the cellular phase of inflammation controlled by?
The neutrophil.
Enter tissues - trilobed nuclei stain purple
How do neutrophils escape vessels?
- 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
What adhesion molecules help with neutrophil vessel escape?
- 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)
How do neutrophils move through interstitium?
Chemotaxis - along an increasing chemical gradient of chemoattractants (e.g. bacterial peptides and inflammation mediators)
What is the function of neutrophils?
Phagocytosis (cover in MEH, revisit) and release of inflammatory mediators. Also releases debris from phagocytosis to dissolve in blood via exocytosis.
How do neutrophils recognise what to phagocytose?
- Opsonisation
- Pathogen gets covered by FC and C3b opsonins
- Receptors found on neutrophil surface = binds to introduce neutrophil to pathogen
What are neutrophil oxygen-dependent killing mechanisms?
- Reactive oxygen intermediates (superoxide, hydroxyl radical, hydrogen peroxide)
- Reactive nitrogen intermediates (nitric oxide and dioxide)
What are some oxygen-independent killing mechanisms?
- Lysozyme
- Hydrolytic enzymes
- Defensins
How is the cellular phase effective?
- Removal of pathogens and necrotic tissue
- Release of inflammatory mediators
What are inflammatory mediators?
Chemical messengers that control and co-ordinate the inflammatory response. Have overlapping functions.
What do inflammatory mediators originate from?
- Activated inflammatory cells
- Platelets
- Endothelial cells
- Toxins
What mediates vasodilatation?
- Histamine
- Serotonin
- Prostaglandins
- Nitric oxide
What mediates vascular permeability?
- Histamine
- Bradykinin
- Leukotrienes
- C3a & C5a
What mediates chemotaxis?
- C5a
- Tumour necrosis factor
- IL-1
- Bacterial peptides
What mediators are pyrogens?
- Prostaglandins
- IL-1 and IL-6
- TNF-a
What inflammatory mediators induce pain?
- Bradykinin
- Prostaglandins
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
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)
How is fever brought down?
NSAIDs - block cyclo-oxygenase enzymes and therefore production of prostaglandin so that fever is reduced
What are the differences between viral and bacterial leucocytosis?
Viral: lymphocytes
Bacterial: neutrophils
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!
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
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
What causes appendicitis?
- Blocked lumen from faecolith
- Accumulation of bacteria and exudate
- Increased pressure can lead to perforation
What causes pneumonia?
(Streptococcus pneumoniae
Haemophilus influenzae)
Buildup of exudate in lungs - impairs gas exchange. Causes sputum, fever, shortness of breath. Neutrophils in alveoli.
What are risk factors for pneumonia?
- Lung conditions (asthma, COPD)
- Smoking
What causes bacterial meningitis?
(Neisseria meingitides)
Inflammation + exudate in narrow meningeal space
Causes headache, photophobia and altered mental state
What are abscesses?
Accumulation of dead neurophils - liquefactive necrosis)
Can compress surrounding structures and cause pain and duct blockages
What serous cavities can get inflamed?
- Pleural and pericardial space (effusions)
- Peritoneal space - ascites
Exudate into serous cavities.
What is hereditary angio-oedema?
- Inherited deficiency of C1-esterase inhibitor so patients have attacks of itchy oedema and intestinal oedema.
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)
What is chronic granulomatous disease?
- Phagocytes unable to generate superoxide
- Cannot kill bacteria
- Chronic infections when young
What are medicolegal autopsies?
- Performed on behalf of HM Coroner
- No consent needed
What are forensic autopsies?
- Also coroner’s post mortems
- Performed in suspicious deaths (eg. murders, suicides)
What are hospital/consent autopsies?
- Need consent from next of kin
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)
What is involved in an autopsy?
- History
- External examination: natural disease? injury? imaging?
- Internal examination: all systems examined unless no consent
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
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
What are some causes of sudden death (heart)?
- Coronary thrombosis (rupture causes haemopericardium)
- Valvular disease
- Cardiomyopathies
- Aortic aneurysms that rupture
- DVT
What are causes of sudden death (lungs + other)?
- Bronchopneumonia
- Pulmonary embolism (DVT)
- Peritonitis
What is neuropathology?
Branch of autopsy dealing with trauma, neurodegenerative disease & research
What is paediatric pathology?
Child autopsies.
- In-utero & perinatal deaths
- Sudden infant death
- Suspicious deaths
- Medicolegal & safeguarding issues
- Provide answers for families
