Pathology Flashcards
What is inflammation?
The local physiological response to tissue injury. No the disease itself, but a manifestation of disease.
What is a benefit of inflammation?
The destruction of invading microorganisms and the walling off an abscess cavity, preventing spread of infection
What is acute inflammation?
The initial and often transient series of tissue reactions to injury.
What is chronic inflammation?
The subsequent and often prolonged tissue reactions following initial response.
What are the steps of acute inflammation?
1) Initial reaction of tissue to injury
2) Vascular - dilation of vessels & increased blood flow
3) Exudative - vascular leakage of protein-rich fluid and neutrophil attracted to site of injury by chemotaxins
4) Neutrophil polymorph - migrate to plasmatic zone(area near wall of blood vessel)
- adhesion to endothelium
- emigration, neutrophils pass through endothelial cells onto basal lamina
- Diapedesis (passage of RBCs through intact walls of capillaries) RBCs may also escape
Outcomes of acute inflammation?
1) resolution - restoration of tissue
2) suppuration - formation of pus leading to abscess and scaring
3) organisation - replacement by granulation tissue (new connective tissue), new capillaries grow into inflammatory exudate, macrophages migrate, fibrosis occurs
4) progression - causative agent not removed so moves to chronic inflammation
What are the causes of acute inflammation?
1) microbial infections (pyogenic bacteria, viruses)
2) Hypersensitivity (parasites, tubercle bacilli)
3) Physical agents (trauma, ionising radiation, heat, cold)
4) Chemical (corrosives, acid)
5) bacterial toxins
6) tissue necrosis (ischaemic infarction - block in blood vessels)
Appearances of acute inflammation (5 Cardinal signs):
1) Rubor (redness) - due to dilation of small blood vessels within the damaged area
2) Calor (heat) - due to increased blood flow (hyperaemia), resulting in vascular dilation and delivery of warm blood to the area (systemic fever from chemical mediators)
3) Tumor (swelling) - oedema, accumulation of fluid in extravascular space and inflammatory cells migrating to area
4) Dolor (pain) - from stretching and distortion of tissues due to inflammatory oedema and pus. Prostaglandins and serotonin induce pain.
5) loss of function - inhibited by pain, or severe swelling immobilises tissue
In acute inflammation, what causes increased vascular permeability?
- immediate transient chemical mediators e.g. histamine, bradykinin, nitric oxide, platelet activating factor, C5a, leucotriene B4
- immediate sustained severe direct vascular injury
- delayed prolonged endothelial cell injury e.g. x-rays, bacterial toxins
In acute inflammation, how is the cellular exudate formed?
- Accumulation of neutrophil polymorphs within the extracellular space (histological feature)
1) neutrophils move to sides of vessels (margination)
2) line the walls (pavementing)
2) Pass between endothelial cells
3) pass through basal lamina and migrate into adventitia
What chemical mediators are involved in acute inflammation?
Histamine & thrombin
- released by original inflammatory stimulus cause up-regulation of adhesion molecules on the surface of endothelial cells (increased neutrophil adhesion)
What do these endogenous chemical mediators in acute inflammation cause?
- vasodilation
- emigration of neutrophils
- chemotaxis (movement of organism towards a chemical stimulus)
- increased vascular permeability
- itching and pain
What are the 4 enzymatic cascade systems contained in plasma?
1) complement
2) the kinins
3) coagulation factors
4) fibrinolytic system
What endogenous chemical mediators cause vascular dilation?
Histamine (cause relaxation of muscle through increased Ca2+)
Prostaglandins
PGE2/I2
VIP
Nitric oxide
PAF
What endogenous chemical mediators cause increased vascular permeability?
Transient phase - histamine
Prolonged phase - bradykinin, nitric oxide
What chemical mediators cause adhesion of leucocytes?
Up-regulation of adhesion molecules on endothelium by IL-8, C5a, Leucotriene B4, PAF
What chemical mediators are involved in neutrophil polymorph chemotaxis?
Leucotriene B4
IL-8
What is the role of neutrophil polymorph in acute inflammation?
1) ingest bacterium
2) bacterium lies within a phagocytic vacuole (phagosome)
3) lysosomes fuse with phagosome and enzymes digest bacteria (phagolysosomes)
4) Bacterial debris released from neutrophil polymorph and lysosomes replenished
What are the special macroscopic appearances of acute inflammation?
1) serous
2) suppurative inflammation - producing pus
3) membranous inflammation
4) pseudomembranous inflammation
5) necrotising (gangrenous) inflammation - tissues start to die
What are the systemic effects of inflammation?
- Pyrexia (increased body temp)
- constitutional symptoms
- weight loss
- reactive hyperplasia (enlargement) of the reticuloendothelial system (monocytes and descendants)
- haematological changes
- amyloidosis (build up of protein amyloid stopping organs from working properly)
What is cellulitis?
The skin over the lateral part of the foot is red (erythema) due to vascular dilatation due to acute inflammation
What is early acute appendicitis?
Appendix is swollen due to oedema, the surface is covered by fibrinous exudate and the blood vessels are prominent due to dilation
(good example of acute inflammation)
What is a granuloma?
A small area of chronic inflammation characterised by collection of macrophages (& T helper cells).
How are granulomas formed?
In response to chronic inflammation
1) antigen from causative pathogen is taken up by macrophage
2) then presented to CD4+ helper T cells
3)CD4+ helper T cells convert to TH1 subtype
4) TH1 cells secrete IL-2 & INy
5) T cells proliferation and macrophage activation
6) macrophages & T-cells secrete TNF alpha
7) Increased accumulation of inflammatory cells
What are the types of granulomas?
Caseating
- central region of necrosis
- usually in lungs
- form in response to infection
- appear ‘cheese-like’
Non-caseating
- No central region of necrosis
- occurs more commonly
- response to contact with foreign material, sarcoidosis (small patches of swollen tissue to develop in body’s organs) and Crohn’s disease
What are the causes of chronic inflammation?
- resistance of infective agent (TB)
- endogenous material (necrotic tissue)
- exogenous material ( asbestos, silica)
- autoimmune conditions
- primary granulomatous diseases
- transplant rejection
- continued acute inflammation
What cells are involved in chronic vs acute inflammation?
Acute
- neutrophils, monocytes
Chronic
- B lymphocytes -> plasma cells -> antibodies
- macrophages -> cytokines
- t lymphocytes -> cell mediated immunity
- granulomas -> aggregate of epithelia histiocytes
What is the macroscopic and microscopic appearance of chronic inflammation?
Macroscopic appearance:
Chronic ulcer
Chronic abscess cavity
Granulomatous inflammation
Fibrosis
Microscopic appearance:
Characteristically lymphocytes, plasma cells and macrophages
Exudation is not a common feature
Evidence of continuing destruction
Possible tissue necrosis
Who performs which autopsies?
Histopathologists
- hospital autopsies
- coronial autopsies (natural deaths, drowning, suicide, accidents, car accidents)
Forensic pathologists
- coronial autopsies (homicide, death in custody, neglect)
What are fibroblasts?
Produce collagenous connective tissue in scarring following some types of inflammation
(produce collagen)
What are macrophages?
- WBCs
- live longer than neutrophils
- phagocytose debris and bacteria
- transport material to lymph nodes
- may present antigen to lymphocytes
e.g., kupffer in liver, osteoclast, microglial
What are lymphocytes?
- long lived cells
- very small cytoplasm as don’t produce proteins
- plasma cells produce antibodies
What are neutrophil polymorphs?
- short lived cells
- first on the scene of acute inflammation
- cytoplasmic granules full of enzymes that kill bacteria
- die at site of inflammation and then phagocytose
What is the sequence of chronic inflammation?
1) no or very few neutrophils
2) macrophages and lymphocytes, then usually fibroblasts
3) can resolve if no tissue damage but ends up with repair and scarring
Is Tuberculosis acute or chronic inflammation?
Chronic inflammation
but no initial acute inflammation (no neutrophils)
- just has macrophages
How to treat inflammation?
- ice (stops blood vessels dilating and fluid being exudated)
- Anti-histamine -> block histamine reducing inflammation
- ibuprofen -> inhibit prostaglandin synthetase
- steroid cream (prevent the persons system from reacting to the bacteria)
What is resolution and repair?
Resolution
- initiating factor removed
- tissue undamaged or able to regenerate
Repair
- initiating factor still present
- tissue damaged and unable to regenerate
What does repair involve? And examples of when organs cannot resolve?
- replacement of damaged tissue by fibrous tissue (when it can’t regenerate)
- collagen produced by fibroblasts
Examples: - heart after myocardial infarction
- brain after cerebral infarction
- spinal cord after trauma
What is healing by 1st intention?
when the wound edges are approximated e.g., sutures, stitches
(leaves only a thin scar)
incision -> exudation of fibrinogen -> weak fibrin joint -> epidermal regrowth and collagen synthesis -> strong collagen join
What is 2nd intention healing?
A tissue loss injury or another reason that the wound margins are not apposed
- can’t bring edges together
- granulation tissue to fill in defects and repair specialised tissues lost
- loss of tissue -> granulation tissue -> organisation -> early fibrous scar -> scar contraction
Which cells regenerate?
- Hepatocytes
- pneumocytes
- all blood cells
- gut epithelium
- skin epithelium
- osteocytes
Which cells don’t regenerate ?
myocardial cells
neurones
Why don’t blood clots form all the time?
1) Laminar flow - cells travel in the centre of arterial vessels and don’t touch the sides
2) Endothelial cells - that line vessels are not ‘sticky’ when healthy
What is a thrombosis?
The formation of a solid mass from blood constituents in an intact vessel in a living person.
What is thrombosis caused by?
Virchow’s triad:
1) change in vessel wall
2) change in blood flow
3) change in blood constituents
What is the process of the formation of an arterial thrombosis?
1) Atheromatous plaque may have a fatty streak
2) Plaque grows and protrudes into the lumen causing turbulence in blood flow
3) Turbulence results in loss of intimal cells
4) Fibrin deposition and platelet clumping occurs
5) Keeps going to form first layer of thrombus
6) This layer allows for the precipitation of a fibrin mesh -> traps RBCs
7) Protrudes further causing more turbulence and more platelet deposition
8) Thrombi grow in direction of blood flow (propagation)
What are the differences between venous and arterial thrombosis?
Venous thrombosis:
- thrombi begin at valves
- commonly caused by stasis
- when blood pressure falls, flow through veins slow, allowing for a thrombus to form
- low pressure
- mainly made of RBCs
- Anti-coagulants (warfarin)
Arterial Thrombosis:
- commonly caused by atheroma
- high pressure
- mainly made of platelets
- can lead to MI/stroke
- anti-platelets
What are the fate of thrombi?
1) Resolve - body dissolves and clears it
2) Organised - becomes a scar, results in slight narrowing of the vessel lumen
3) Recanalisation - intimal cells may proliferate, capillaries grow into thrombus and fuse to form larger vessels
4) Embolus - fragments of the thrombus break off into the circulation
What is an embolism?
Mass of material in vascular system that lodges in a vessel and blocks lumen
What are the causes of an embolism?
- most commonly a thrombus (e.g. deep vein thrombosis)
- air (from intravenous fluids)
- cholesterol crystals (atheromatous plaque)
- tumour
- amniotic fluid
- fat (severe trauma with multiple fractures)
Types of emboli:
1) Venous embolism - will travel to the vena cava and lodge in pulmonary arteries
(cannot enter arteries because blood vessels in lungs split down to capillaries)
2) Arterial embolism - can travel anywhere downstream of its entry point
What is ischaemia?
A reduction of blood flow to a tissue or part of the body caused by constriction or blockage of blood vessels supplying it without any other implications (just reduction in blood flow)
What is an infarction?
It is the reduction in blood flow to a tissue that is so reduced that it cannot even support mere maintenance of the cells in that tissue so they die. (reduction in blood flow + death)
How is infarction caused?
Usually a macroscopic event caused by thrombosis of an artery, stopping blood flow to cells
How does aspirin help with thrombosis?
Low dose aspirin inhibits platelet aggregation, so this can be prescribed to reduce the risk of thrombosis
What is atherosclerosis?
Formation of atherosclerotic plaques in the intima of systemic (opposed to pulmonary) arteries.
(common in high pressure systems such as aorta and systemic arteries)
What are the risk factors of atherosclerosis?
Hyperlipidaemia (hypercholesterolemia) most important risk factor
Smoking
Hypertension
Diabetes
Male sex
Increasing age
Formation of atherosclerosis
1) Endothelial cell dysfunction (increased cholesterol)
2) High levels of LDL in the blood accumulate in arterial wall
3) Macrophages attracted to site of damage and take up LDL liquid to form foam cells
4) Formation of a fatty streak
5) Activated macrophages release products (cytokines)
6) WBCs die and more WBCs are sent, the dead cells build up to form a plaque.
7) Smooth muscle proliferation around lipid core (muscle cells form over top layer of plaque) and form a fibrous cap (collagen)
8) After growth of plaque, the fibrous cap ruptures and plaque comes into contact with the blood causing a blood clot to form.
(only in arteries)
phase1 - damage of endothelial layer
phase 2 - formation of fibrous cap
How is a venous thrombus formed?
Mainly around valves due to turbulent blood flow
1) damage to endothelial cells in the vessel causes cells to lift from vessel wall, exposing collagen
2) platelets then begin to stick to this exposed collagen and release chemicals which cause platelet aggregation and starts off cascade of clotting proteins
3) RBCs then get trapped within the aggregating platelets
4) clotting factors join the red blood cells and platelets, and the clotting cascade forms a large protein molecule fibrin, which then gets deposited and forms the clot
5) positive feedback loop -> can end up causing a thrombus, blocking the artery
What is end artery supply?
AN organ that only receives blood supply from one artery so if thrombus forms the whole blood supply to an organ is in infarct.
Except some organs have multiple arterial supplies:
- liver -> portal vein and hepatic artery
- lungs -> pulmonary arteries and bronchial arteries
- brain -> circle of willis
What is an atheroma?
- The fatty material which forms deposits in the arteries.
- Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and risk of thrombosis.
