Week 10 - Infection and inflammation Flashcards

(69 cards)

1
Q

What are the 5 cardinal symptoms associated with tissue damage?

A
  • Redness
  • Pain
  • Heat
  • Loss of function
  • Swelling
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2
Q

What substances are involved in vascular resistance / arteriolar tone?

A

Noradrenaline + sensory nerves = constrictor / dilator factors

Endocrine and pancreatic hormones

pO2 + pCO2

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3
Q

What happens during the acute imflammatory state?

A

Inflammatory vasodilators override arteriolar tone influencers (from tissue fluid, tissue cells, nerve endings, leukocytes)

Histamine (skin mast cells –> vasodilation)-REDNESS

Bradykinin (vasodilation and endothelial prostaglandin release + stimulation of nociceptors)-PAIN

Vasodilator peptides in sensory nerves (substance P, VIP, CGRP)

Each = + blood flow and temperature

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4
Q

What happens during microcirculation in acute extravasation?

A

All cells = contractile elements

Arteriolar endothelium = even protein distribution

Venular endothelium = selective distribution around pores

Venular site = low hydrostatic pressure and large SA

Oedema from plasma protein and fluid leakage into extracellular space -SWELLING

Endothelial damage

Postcapillary venule pore modulation

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5
Q

What happens during microcirculation in intermediate extravasation?

A

Acute inflammation = =2 hours

Tumour necrosis factor released

Complement 5 activation, attracting neutrophils to site of injury

Cytokines activate vascular endothelium and interleukin-8 release

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6
Q

What happens during acute modulation of venular permeability when it is + and -?

A

+ venular permeability = Ca2+ elevated, contracting pore proteins

Histamine, Bradykinin, Leukotriene C4 / D4, Platelet activating factor

  • venular permeability = pore proteins relax by cyclic AMP

‘B’2-adrenoceptor agonists, PGI2

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7
Q

What happens during the triple response?

A

Flush – histamine release from mast cells and vasodilation

Flare - + vasodilation and redness, sensory nerve orthodromic activation (pain + itching), antidromic activation of branches –> P, CGRP, VIP release

Wheal – oedema in damaged area, protein extravasation

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8
Q

What happens during neutrophil-dependent extravasation?

A

Release of IL-8 from activated endothelium

Stimulate neutrophil G protein coupled chemokine receptor

Permits interaction between integrin and endothelial Ig CAM

Promotes adhesion of neutrophil to endothelium (2 hours after injury)

Neutrophils cross endothelium (diapedasis) and migrate towards chemoattractant at site of injury

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9
Q

What happens when there are + neutrophils?

A

+ phospholipase A2 regulation and cyclooxygenase–2 induction

+ blood flow

IL-1 and TNF release, activating endothelial receptors

Endothelial-leukocyte adhesion molecule production for monocytes –> conversion into macrophages

Induction of Nitric Oxide Synthase II

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10
Q

What happens during the late phase?

A

Cytokines from activated neutrophils and macrophages = degradation of damaged tissue + site of injury preparation for healing

Breakdown of tissue for repair = lead by leukocyte production of proteolytic enzymes and oxygen radicals

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11
Q

What is the role of cytokines in injury response?

A

Act centrally to pyrogenic response –> receptors in hypothalamus (fever)

Elevate corticosteroids as ‘stress response’, promoting inflammation in short-term

+ hepatic protein

Bone marrow stimulation

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12
Q

What happens during the proliferative / granulation phase?

A

Growth factors produced by macrophages and platelets

Granulation of tissue caused by proliferation of + cells

Macrophages, fibroblasts + neovascularisation = in loose collagen matrix

Failure to stop phase = rheumatoid arthritis, scleroderma –> calcification and ossification of cartilage

Fibroblasts = produce collagen for structure

Blood vessel proliferation = for oxygen and nutrient supply

Cell movement in site of injury stimulated by metalloproteinases

Angiogenesis = inhibited by methotrexate

Affected by sex hormones

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13
Q

What happens during the maturation phase?

A

Remodelling of tissue

Macrophages involved

Reduced vascularisation = - nutrient demand and – tissue metabolic activity

Collagen remodelling and reinnervation by nerves = + tissue strength and sensation

Scar tissue = caused by lack of elastin

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14
Q

How do NSAIDS work?

A

Cyclooxygenase inhibitors:

  • Reduces inflammation by supressing PG synthesis
  • Reduce vasodilation and hyperaemia
  • Reduce hydrostatic pressure in venules
  • Reduce protein leakage into extracellular space
  • Reduce pain
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15
Q

How do glucocorticoids work?

A
  • Inhibit inflammation with long-term treatment
  • Reduced cell adhesion molecule expression
  • Reduced chemotaxis of neutrophils
  • Reduced cytokine production
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16
Q

How do selective COX-2 inhibitors work?

A
    • prostanoid and thromboxane A2 levels
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17
Q

What are the functions of skin?

A

External damage protection (UV)

Barrier (waterproof)

Sensation

Metabolic (subcutaneous fat energy store)

Thermoregulation (insulation)

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18
Q

What are the 3 layers of the skin and how are they structured?

A

Epidermis (epithelium) –> stratified squamous keratinised

Dermis (connective tissue) –> dense, irregular connective tissue (fibroblasts, collagen I, elastin, blood, nerves, receptors), divided into papillary and reticular dermis

Hypodermis / subcutis (fascia) –> adipose tissue and main blood supply

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19
Q

What are the 5 epidermis keratinocyte layers?

A
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20
Q

What are the epidermis barriers?

A

Tight junctions (prevent paracellular diffusion)

Desmosomes and hemidesmosomes (mechanical and sheer)

Keratin (microorganisms)

Phospholipid (waterproof)

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21
Q

How do the 5 epithelial keratin layers form?

A

Basal layers divide

Differentiate as they rise through layers

Intermediate layers produce keratin and lose organelles and nucleus, becomming stratum corneum flattened cells

Hemidesmosomes tether basal layer to dermis

Intermediate layers have + desmosomes

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22
Q

What are the types and properties of keratinocyte cancers?

A

Basal cell carcinoma (approx. 80%) from basal layer

Squamous cell carcinoma (approx. 20%) from upper epidermal layers

Both are curable

Linked to total cumulative sun exposure

Common on head, neck and hands

In people of all skin colours

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23
Q

What are the properties of keratinocytes and melanocytes?

A

Keratinocytes: 95% of cells

Stratified squamous keratinising epithelial cells

Produce keratin

Melanocytes:

pigment synthesising cells responsible for skin and hair colour

Neural crest derived cells lying in the stratum basale

Melanosomes in cytoplasm contain melanin and are passed to keratinocytes – scattering of UV light

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24
Q

What are the properties of langerhans cells and merkel cells?

A

Langerhans cells:

All layers and upper dermis-prominent in spinosum. Bone marrow derived. Dendritic, antigen presenting cells-migrate to regional lymph nodes and communicate with the immune system.

Merkel cells:

Clear cells in stratum basale. Plentiful in touch areas. Connected to keratinocytes and afferent nerves. Neuroendocrine function

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25
What are the 4 skin cell types?
Keratinocytes Melanocytes Langerhans cells Merkel cells
26
What are examples of skin pigmentation disorders?
Lentigo maligna Albinism: Lack of melanin due to lack of enzyme required to make melanin: tyrosinase Vitiligo: macules of de-pigmented skin enlarging over time. Cause unknown
27
What are the properties of a melanoma?
Asymmetry Border Colour Diameter
28
How does the skin stay on?
+ surface area from interdigitation between epidermis and dermis Epidermis and dermis adhered by hemidesmosomes Basement membrane between epidermis and dermis
29
What are the properties of the dermis?
Dense connective tissue: collagen 70% Papillary: conical papillae (rete ridges), richly vascularised (capillaries), lymph and nerve Reticular: Horizontal collagen and elastin fibres Contains hair and gland structures
30
How is skin varied?
_Thin skin:_ - Most locations - + eccrine glands and thin keratin layer - Less well defined rete ridges _Thick skin:_ - Fingertips + soles of feet - Thick epidermis and keratin layer and well developed rete ridges - + eccrine glands, no hair _Hairy skin:_ - Thin epidermis and lots of hair follicles and sebaceous glands
31
What are the skin specialisations?
32
What is the main virus structure?
Simple Nucleic acids Proteins Lipids No organelles
33
What are the properties of virus metabolism?
Metabolically inert Rely on host cell Are obligate intracellular parasites
34
What are the properties of virus replication?
Independent component part synthesis Can be in separate parts of cell Under separate control Assembly into new particles
35
What are the properties of virus nucleic acids?
DNA --\> double / single stranded, circular / linear, 3kb-200kb RNA --\> ds / ss, ss = +ve / -ve polarity, linear / segmented, 5kb-10kb
36
What are the functions of proteins in viruses?
Capsid formation --\> symmetry (icosahedral / helical) Attachment --\> specific cellular receptor and viral ligand interaction, determines viral tropism (preference to infect certain cell types) Enzymes --\> macromolecular synthesis enzymes Interference with cell function --\> i.e. stop apoptosis, avoid immune recognition
37
What are the functions of the lipid envelope of viruses?
From host cell membranes Needs to contain external attachment proteins Loss of infectivity if envelope stripped Virus more fragile if enveloped
38
What is virus clasification based on?
Nature of genetic material Nature of capsid Enveloped Size / shape Families, genera, strains
39
What are the stages of viral replication?
Attachment (cellular receptor / viral ligand) Entry (endocytosis, fusion) Uncoating Macromolecular synthesis (multiple viral genome and viral protein copies (requiring +ve ss RNA)) Assembly Release (budding (yielding enveloped virus), cell lysis)
40
What is a virion? What is positive / negative polarity of RNA? What is a viral tropism?
Virion = mature virus particle --\> nucleic acid, protein coat (capsid), lipid envelope -ve polarity = can be translated at a ribosome Viral tropism = specificity of a virus to a specific host cell
41
What are the anti-viral effects of antibodies?
Antibodies = block entry and binding to cells, activate intra-cellular degradation via TRIM21 Antibodies + complement = damage enveloped viruses, opsonisation for phagocytosis Antibody bound to infected cells = antibody-dependent cellular cytotoxicity
42
What is antigenetic shift?
Recombination between 2 different viruses, forming a totally new one
43
What are the functions of interferons?
Type 1 = enhance HLA class 1 protein expression and activate natural killer cells Interferons produced by infected cells bind to receptors on uninfected cells Uninfected cell is resistant to viral cell replication Protein synthesis is inhibited in cell and viral mRNA is degraded
44
How do cytotoxic T cell work?
Have CD8 receptors on surface Viral cell proteins degraded by protease, forming peptides Peptides are expressed on infected cell surface HLA class 1 proteins Cytotoxic T cells bind to the HLA class 1 protein and kill infected cell
45
How do natural killer cells work?
Have kill activating receptor molecules Have kill inhibition receptor molecules too Binding to normal cell = don’t kill as stronger inhibition signal Abnormal cells = kill signal is dominant
46
How is an enveloped RNA virus formed?
47
What are the criteria for screening a population?
1. The condition sought should be an important health problem 2. There should be an accepted treatment for patients with recognized disease, and treatment should be better at an earlier stage 3. Facilities for diagnosis and treatment should be available 4. There should be a recognizable latent or early symptomatic stage 5. There should be a suitable test or examination 6. The test should be acceptable to the population 7. The natural history of the condition, including development from latent to declared disease, should be adequately understood 8. There should be an agreed-upon policy on whom to treat as patients 9. The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole 10. Case-finding should be a continuing process and not a “once and for all” project.
48
What are the benefits of screening programmes?
1. Screening may produce earlier diagnoses 2. Earlier diagnosis may improve prognosis for those who develop disease 3. In some cases disease may be prevented 4. If treating early is cheaper than treating late, then screening may sometimes save money
49
What are the disadvantages of screening programmes?
1. Screening programmes cost money 2. Screening may induce anxiety in the well 3. Tests my cause harm directly 4. No screening test will detect all disease 5. A screen negative patient may delay presenting symptomatic disease if falsely reassured 6. There will be false positives 7. There will be over diagnosis
50
What is lead time bias?
Time between when a disease can be detected through screening and when it can be clinicaly detected
51
What is length bias?
52
What are the 4 outcomes of virus infection?
Cell death --\> cytolytic or cytocidal infection (Rhinovirus) Chronic infection --\> continuous viral replication in cell, cell survives (Hep B) Latency --\> No replication of virus, no viral protein production, always infected once infected, reactivation of virus replication can occur, primary and secondary infections (herpes) Transformation --\> cell immortalisation (Epstein-Barr virus)
53
How are viruses spread to hosts?
Skin Mucosal surfaces Respiratory tract Gastrointestinal tract Placenta
54
How are viruses spread within hosts?
Skin – vesicles Respiratory tract – droplets Gastrointestinal tract – saliva, faeces Urogenital tract – urine, semen, female genital tract secretions Blood – BBV incl HBV, HCV, HIV Breast milk
55
What is cytolytic infection? What is cytopathic effect?
Where a cell is destroyed Change in host cell structure caused by viral infection
56
What happens during hypertrophy?
Increase in the size of cells Can be physiologic/pathologic No new cells-just bigger Cells that don’t divide e.g. Cardiac and skeletal muscle Examples: exercise, hypertension
57
What happens during hyperplasia?
Increase in the number of cells Breast development at puberty/liver regeneration after resection/wound healing Eg psoriasis leads to thickened skin
58
What do hypertrophy and hyperplasia both result in and when do they occur at the same time?
Both adaptations individually result in enlargement of tissue Example of both together: Uterine enlargement (hypertrophy) during pregnancy is a consequence of smooth muscle hypertrophy and hyperplasia
59
What is atrophy?
Shrinkage in cell size due to loss of cell substance Functionally diminished but alive Eg immobilised or aging limb muscle
60
What is involution?
Reduction in number of functioning cells Due to reduction in functional demand (myometrium of uterus post partum) Usually by programmed cell death (apoptosis)
61
What is metaplasia?
Change in type of cell - reprogramming of stem cells Survival mechanism in response to injury e.g. Smoking Specialised function is lost Can predispose to neoplasia Reversible + cancer risk
62
What is the purpose of acute inflammation?
**A protective mechanism that functions to:** Eradicate cause of injury Remove damaged cellular material Initiate repair process
63
What are the 3 steps of acute inflammation?
**1. Vasodilation** Slowing the local blood flow to the area (allowing time for plasma containing mediators to leave and for neutrophils to come into contact with the vessel wall) Enabling cells to contact the capillary endothelium Generating heat and redness **2. Increased vascular permeability** Allowing plasma carrying mediators out Causing swelling (oedema/tumor/turgor) **3. Cellular activation and migration** Neutrophils are activated to migrate from the vessels. They have a great capacity for phagocytosis Short lived so need to be replaced
64
What are the outcomes of acute inflammation?
Resolution --\> minimal damage, normal tissue restored Repair --\> damage too severe (scar forms) Chronic inflammation --\> persistent stimulus Abscess forms
65
What are the 3 types of cells?
Labile – replicate throughout life --\> i.e. skin (resolve) Stable – Non-dividing in normal circumstances but capable of regeneration --\> i.e. liver and kidney (resolve or scar) Permanent – non-dividing cells --\> i.e. neurons and heart (always scarring)
66
What happens during fibrosis?
Granulation tissue --\> macrophages + fibroblasts + new blood vessels Fibrosis + scar formation --\> matrix laid down by fibroblasts, + collagen laid down forming scar to strengthen tissue Remodelling --\> reduction in number of vessels so pale scar remains
67
What is the process of wound healing?
Inflammatory phase --\> macrophages producing growth factors for next phase Proliferative phase --\> granulation tissue, fibroblasts secrete matrix components + growth factors for angiogenesis, regrowth of epithelial cells over wound Remodelling --\> - vascularity, wound contraction
68
What are the functions of growth factors?
- Mediators of repair - Stimulate cell proiliferation, differentiation and maturation
69