MP321 week 5 Flashcards

(127 cards)

1
Q

functions of the skin (8)

A
  • a physical barrier to noxious agents and the entry of pathogens
  • an immunological barrier to the ingress of pathogenic organisms
  • assists retention of heat and regulation of temperature
  • retains moisture and maintains osmotic balance within the Body
  • a sensory organ- touch, social contact
  • excretion
  • vitamin D production
  • protection from UV in sunlight
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2
Q

epidermis

A

outer most layer waterproof codified outer layer of keratin proteins and lipids

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3
Q

dermis

A

supporting region of the skin just below the epidermis
dermis-blood and lymph vessels
nerves and hair roots (hair follicle with sebaceous gland and muscle in Demis)
sweat glands- apocrine and eccrine

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4
Q

eccrine gland

A

in the dermis layer
secrete directly onto skin surface
thermoregulation, salt excretion, antibacterials

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5
Q

apocrine gland

A

in the dermis layer
bud fatty secretions off into enclosed areas like hair follicles
especially found in axilla and public areas

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6
Q

layer of the epidermis

A

top nuclear squamous layer
granular layer
spindle layer
germinal layer- inner most

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7
Q

top nuclear squamous layer

A

Essentially dead as anuclear. Tough because of keratin, tightly joined. A tough waterproof barrier to the outside world and pathogens
Dead skin cells constantly shed off making dust, which is fed on by dust mites eat it and cause of allergy

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8
Q

granular layer

A

Where cells have vesicles containing keratin fibre. Gets its name from its granular appearance under a microscope. Keratin strengthens them making them tough

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9
Q

spindle layer

A

spindle layer cells form tight junctions anchored with adhesion proteins, cells glued into a sheet-like structure
differentiate and rise up further
this layer contains langerhans cells (APC or macrophages) specific to the skin

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10
Q

germinal layer

A

is where the stem cells replicate and constantly divide and renew
then they migrate upwards based on a potential difference of a very small charge
also melanocytes (which produce pigment)

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11
Q

the pilosebaceous unit

A

Look in more detail of an apocrine gland
The hair follicle bases is in the dermis layer with the hair poking through the epidermis and out
Hair follicles are housed in the pilosebaceous unit.
2. The arrector muscle. When the arrector muscle contracts it pulls the base to an upright position, making the hair stand up-goosebumps
3. The pilosebaceous unit produces sebum- a sticky substance secreted on surface skin.
It is antibacterial and has low pH. It contains proteins and waterproofing lipids

Can change lipid content to modulate sweat evaporation to control thermoregulation
If there is obstruction of sebum secretion it may become infected, causing acne and other skin conditions

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12
Q

meissner corpuscle

A

near the surface of the skin
responds to light pressure

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13
Q

pacinian corpuscle

A

deep in the skins layers
responds to deeper pressure

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14
Q

merkel cells

A

middle skin layer
respond to sustained light pressure

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15
Q

innervation of glabrous (non-hairy) skin

A

by fast conducting, low threshold mechanics-receptors (LTMRs) mediates sense of touch, vibration and pressure
specialised sensory nerves in the skin:

merkel cells
pacinian corpuscle
meissner corpuscle

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16
Q

examples of glabrous skin

A

non hairy
palms and soles of feet
rich in sensory nerves

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17
Q

examples of hairy skin

A

major part of body surface
back, scalp etc

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18
Q

microenvironment

A

different skin regions vary greatly in their appearance and in the amounts of moisture and oiliness they typically carry
temperature and pH also

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19
Q

wound healing stages (4)

A
  • hemostasis
  • inflammation
  • proliferation
  • remodelling
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20
Q

hemostasis in wound healing

A
  • fibrin is released by platelets
  • it is cross linked to make a plug to stop bleeding
  • helps prevent infections taking hold
  • langerhan cells patrol the local area and modulate response
  • release of histamine via mast cells causes vasoconstriction
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21
Q

inflammation in wound healing

A
  • chemotactic factors are released into the bloodstream
  • monocytes move in by diapedesis
  • more neutrophils are attracted
  • mast cell activation
  • a cycle of inflammation
  • combats opportunistic infections
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22
Q

proliferation in wound healing

A
  • helps to form a scab on top of the wound
  • scab detached as skin grows underneath
  • endothelial cells proliferation promotes angiogenesis
  • fibroblast proliferation fills the underlying connective tissue and the skin
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23
Q

remodelling of the skin

A
  • skin repairs itself at the surface
  • wound edges come together to form a continuous barrier
  • healing continues underneath
  • myofibroblasts make pseudopods and migrate forward dragging cells behind them forward
  • gradually this enables the ends to come together
  • can take months to heal fully
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24
Q

factors directly affecting wound healing

A

Body site
Infection
Vascular supply
Oxygenation
Mechanical stress
Desiccation
Oedema

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25
factors indirectly affecting wound healing
Age and nutrition, medication, alcoholism, drug abuse, hygiene Diabetes Autoimmune diseases Venous stasis Predisposition to keloids (prominent scar tissue) Some genetic skin diseases Immunocompromised state (AIDS, cancer) Obesity, immobility, vasculitis, neuropathy,
26
tanning
- UV light exposure induces double stranded breaks in DNA in keratinocytes - causes activation of a protein called p53(which is a tumour suppressor gene) - transcription of proopiomelaocortin (POMC) - POMC is cleaved into 2 species- B-endorphin acts as a local analgesic and A-melanocyte stimulating hormone (MSH) causes melanocytes to produce a pigment - melanosomes transfer pigment to keratinocytes - melanin absorbs UV light before it can reach DNA and damage it
27
melanomas
Superficial spreading melanoma Amelanotic melanoma Nodular melanoma Acral lentiginous melanoma Uveal melanoma
28
skin microenvironment and the human microbiota
- about 1 million bacteria per cm^2 of skin - thus healthy skin is home to many bacteria, viruses and fungi - together they make up a microbial bio community called the microbiota
29
the skin microbiota
Microbiota composition varies by area Skin folds can affect microbiota Oily skin can also influence this Fungi tend to colonise creases and folds between the toes Bacteria are found all over but particular species have their own favoured niches  Staphylococcus tends to favour enclosed/creases
30
Damage to the skin – Infections: Possible contributions of the microbiota
Skin microbiota can cause skin infections Genetic predisposition can make skin more vulnerable increased sensitivity to particular microbes Change in microbial density/composition more bacteria present mean it is easier to penetrate the skin Metabolic diseases can alter the nutrients on the skin and the vascular supply Change in the type of microbes? Contextual pathogens In a wound, normal microbes can become pathogenic Drug treatments Antibiotic or topical steroids can change growth conditions Overgrowth or harmful bacteria?
31
vesicles
fluid filled blisters the size of a pin head
32
bullae
fluid filled blister like eruptions around 1 cm in diameter
33
acne vulgaris
Common in adolescence but can occur at any time As a result of oily skin and the colonisation of blocked pilosebaceous unit Causes: blockage of the pilosebaceous unit can allow infection (propionium bacterium acnes) and formation of pustules. Signs and symptoms: If the infection is severe and the hair follicle ruptures, scarring can ensue. Treatment: Depending on the severity, a variety of preparations are available. Topical benzoyl peroxide is one treatment, and tetracycline might be considered if symptoms are severe.
34
impetigo
Bacterial infection in the skin: Commonly affects face or extremities following injury. Bullae and or vesicles can form. Very contagious. Causative factors: Usually caused by S. aureus or S. pyogenes. Commonly affects face or extremities in children following injury. Signs and symptoms: Non-bullous type has pinhead pustules on red skin which erupt to give a yellow-brown crust after skin injury. (About 70% of cases) Bullous type has larger blisters which release clear yellow liquid to leave a golden yellow crust (usually S. aureus on intact skin) The golden crust is a key distinguishing symptom Treatment: For most patients, topical treatment with bacitracin or mupirocin, although resistance in some areas. Also perhaps some care in playgroups etc. to avoid crowded conditions where it could spread.
35
ecthyma
Causative factors: Often progresses from untreated impetigo (causing a deeper infection). Seen in homeless folk with poor hygiene, or soldiers in the tropics, especially if an affected area has been enclosed (as in footwear). Also occurs in immunocompromised individuals. Although commonly associated with S. pyogenes and S. aureus, other bacterial species can also be associated with ecthyma. Signs and symptoms: The infection penetrates to deeper layers of the skin causing the appearance of painful ulcers Treatment: Warm compresses and antibiotics e.g. dicloxacillin Treatment is difficult and can take a long time
36
folliculitis
Causes: Infection of hair follicles by S. aureus usually. Often affects beard, armpits, back of the neck, Signs and symptoms: Red pustules (furuncles) form and eventually rupture in a few days. Treatment: Should be self-limiting and resolve naturally. Topical clindamycin and erythromycin on affected areas if necessary and anti-bacterial soap. Larger abscesses (carbuncles) may need to be surgically drained.
37
erysipelas and cellulitis
Erysipelas (superficial infection) and cellulitis (deeper into the skin): Causes: Involves lymphatic vessels. Erysipelas is often caused by S. pyogenes and cellulitis by S. aureus. Can travel through lymph to become a serious systemic condition (therefore than be life threatening) Signs and symptoms: painful, warm, red swelling which forms a well defined plaque. Treatment: Erysipelas: penicillin; cellulitis: dicloxacillin
38
Necrotizing Fasciitis
Even deeper infection Pathophysiology: Infection of subcutaneous tissue which can occur after surgery or trauma. Can be caused S. pyogenes alone but often involves a mixture of bacteria. Signs and symptoms: Starts with warm red skin but lesion rapidly expands vertically and horizontally. The tissue becomes, dark, pustular then necrotic with gangrene. Treatment: Fatal without prompt treatment. Surgical intervention is required along with parenteral antibiotics such as gentamycin and clindamycin rapid expansion of the lesion
39
dermatophytoses
fungal infection Trychophyton rubrum is most common infectious fungus, and most fungal infections involve the genera Trichophyton, Microsporum and Epidermophyton Forms of tinea (fungal skin infections): Tinea pedis (athletes foot) Tinea cruris (jock itch), Tinea capitis (can cause cradle cap in babies) Tinea corporis (also called ringworm) Tinea unguium (onychomycosis) infection of nails Topical treatment: with terbinafine, clotrimazole or econazole
40
Tinea versicolor
Pathophysiology: Caused by the widespread yeast Malassezia furfur, more common in hot climates Signs and symptoms: Results in lightened pigmentation of the skin in upper body and limbs. This can have psychological impact Treatment: selenium sulfide shampoo or topical antifungal agents
41
Candidiasis
Caused by the yeast Candida albicans part of the normal microbiota Associated with immunosuppression Can be associated with poor oral hygiene and dentures Signs and symptoms: Inflammed and itchy membranes in moist mucous tissues such as mouth, vagina, armpits etc. Treatment: topical antifungals, plus possibility of systemic antifungals such as ketoconazole, fluconazole
42
herpes simplex 1
viral infection Pathophysiology: 85% of population have antibodies to HSV type 1. Virus resides in dorsal ganglia, until reactivated. Signs and symptoms: Self limiting eruption around mucous membranes of mouth Treatment: Acyclovir is favoured treatment
43
Herpes: Varicella zoster (chicken pox) and shingles:
viral infection Pathophysiology: during chicken pox, the virus travels to sensory ganglia where it remains for life Signs and symptoms: Pain and paresthesia in an affected dermatome Treatment: Usually resolves with rest and analgesics, but acyclovir can be used, especially if virus is disseminated
44
warts
caused by human papilloma virus (HPV) Warts are benign skin tumors caused by infection with the human papilloma virus (HPV) Have dark necrotized blood vessels (dark specks) at the heart of the wart. There are many strains of HPV. It is a very common virus, and most strains are benign. Common (plane) wart (verruca vulgaris) affects the hands and face and knees and can spread. Plantar wart- (verruca plantaris) grows into the skin of the foot and can cause pain. Warts will often resolve spontaneously, but can be removed by some form of chemical, cryo or surgical ablation. Some strains of genital warts can increase the risk of cervical cancer, but there is now a vaccine against this- Gardasil
45
Molluscum contaginosum:
Pathophysiology: Caused by the pox virus. Transmitted by direct skin contact. Signs and symptoms: Hyperplasia Raised pink, pus filled lesions with a central depression. Treatment: Often resolves spontaneously, but can linger in immunocompromised individuals. Children treated conservatively, but broadly similar treatment options as for warts with addition of curettage and cantharidin.
46
main causes of resistance in TB
Poor compliance Inadequate treatment and diagnosis (“tools”) Poor health care infrastructure Lack of education and knowledge Global location causes severe logistical issues
47
TB spread
inhalation of droplets
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Why the resurgence of TB?
Complex chemotherapy used to treat the disease causes low compliance - old drugs! Drug resistant strains have emerged (M/X/C DR-TB) Strong epidemiological co-existence between HIV and TB as patients who are immuno-compromised easily catch TB (host defences can not fight bacteria in body)
49
Bacterial persistence in TB
After treatment a small percentage of bacteria may remain in a dormant state in macrophage Complex mechanism between host and pathogen These can become reactivated many years later Patients shows no symptoms – carriers 2 - 23% lifetime risk of reactivation to secondary TB Increased by 10% if immuno-suppressed (HIV or immuno-suppressants)
50
treatment of TB
2 phases- initial and continuation
51
initial phase
4 drugs given together daily - “triple therapy” Rifater® Isoniazid (INH) Rifampicin (RIF) Pyrazanimide (PZA) given with ethambutol Duration of 2 months Can be extended until sensitivity testing completed (need to establish is bacteria will respond to drugs) To reduce the bacterial population as rapidly as possible Prevents resistance Helps reduce chance of reactivation (PZA) PZA only active during initial phase due to host immune response lowering pH in macrophages
52
continuation phase
RIF and INH combination used Rifinah® or Rimactazid® Treatment continued for 4 months Helps destroy remaining bacteria left from initial phase Treatment extended for meningitis or resistant TB But regime change is necessary in above cases
53
DOT
Directly Observed Treatment Necessary for patients who cannot comply with regime Ensures the best chance of fighting the infection Regime and doses need to be changed from non-DOT Supervision given 3 times per week not daily
54
mode of action of TB drugs
Main drugs used can be divided into two categories: Bacteriostatic (inhibit growing bacteria) Bactericidal (kill bacteria outright) This distinction is relative and depends on environment e.g. PZA is bactericidal against TB at low pH but bacteriostatic against growing bacteria Bactericidal drugs are more effective at reducing bacterial populations Bacteriostatics are still VERY important (eg ethambutol)
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first line TB drugs
Isoniazid (INH) Rifampicin (RIF) Pyrazinamide (PZA) Ethambutol Streptomycin Superior efficacy with acceptable toxicity
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second line TB drugs
p-Amino Salicylic Acid Fluoroquinolones Capreomycin , kanamycin, amikacin Ethionamide, Prothionamide Cycloserine Less efficacy and/or worse side effects
57
Isoniazid (INH)
1952 Isonicotinic acid hydrazide Targets the ketoenoyl-reductase enzyme InhA in cell wall mycolic acid biosynthesis prodrug – activated to a binding complex with InhA
58
Rifampicin (RIF)
1966 Prevents protein synthesis binding to DNA-dependent RNA polymerase b-subunit Broad spectrum bactericidal activity Helps sterilize “persistors” and active mycobacteria
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Pyrazinamide (PZA)
1952 Bacteriocidal against “persisting” slow growing mycbacteria mode of action unclear but it is a prodrug requiring activation to the acid form pyrizinoic acid (POA) Requires low pH macrophage environment (intracellular)
60
resistance in TB
Occurs rapidly when single drug is used so combination therapy is the standard mechanism via efflux or mutation at the target enzyme or the enzyme which activates prodrug to the active form MDR-TB (INH and RIF) with/out 2nd line drugs XDR-TB (INH, RIF, at least one the second line injectable aminoglycosides and any fluoroquinolone) strains found where completely resistant
61
future TB drugs
New drugs need to be more efficacious Need to reduce the bacterial population faster Need to combat MDRTB and be less prone to inducing resistance Need to destroy persistent bacteria Novel target to prevent cross resistance Need to reduce duration of therapy and increase compliance Need to be CHEAP (90% of patients can’t afford to buy them) Compatible with RIF Suitable for infants
62
Treatment & classification of malaria
Tissue schizontocides- inhibit the growth of the pre-erythrocytic stages of the parasite in the liver. Hence they are sometimes called 'causal prophylactics‘.  type I - anti-folates - inhibits dihydrofolate production - sulfadioxine - dapsone type II - anti-folate - inhibits dihydrofolate reductase - pyrimethamine - proguanil Hypnozoitocides - are only used to eradicate the dormant liver stage of vivax infections – primaquine (UK) Disrupts the REDOX process in the pentose-phosphate pathway Blood schizontocides- act rapidly and only on the erythrocytic stage of the infection. Some used prophylactically but mainly for treating ‘established’ malarial infection Prevent hemozoin formation leading to cell death by binding to heme in the parasite
63
Resistance in malaria
Resistance can develop and thus chemoprophylaxis guidelines vary with destination as does treatment for infection Caused by mutation as active site or pro-drug activation in the chromosome Preventing cellular uptake of the drug Mainly due to Plasmodium falciparum
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Why is treatment difficult and long?
The disease causes many complex symptoms M. tuberculosis has a very complex cell wall Reactivation of “dormant” or “persistent” bacteria
65
what is the most common symptom of an STI
the most common symptom is NO symptoms however some other common symptoms include - a genital rash - a urethral discharge - genital ulceration - lymph node swelling in groin region - a raised core body temperature
66
why are STI rates higher in young people
important drivers include: - cognitive - behavioural - biological
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cognitive development as factor in STI prevalence
younger adult tend to have less life experiences - reduced reasoning or judgement capacity can negatively impact upon decision making processes - tend to be more concrete thinkers -- focussed on immediate circumstances -- reduced ability to plan ahead
68
behaviour as a factor in STI prevalence
- less likely to use condoms - more likely to have multiple or overlapping partners - greater likelihood of substance use leading to riskier sexual practices -na significantly older partner predisposes to a power imbalance -- makes sexual negotiation more difficult -- higher risk of involuntary intercourse and unsafe sex -- higher risk of exposure to STI
69
biology as a factor in STI prevalence
- younger female tend to be more biologically susceptible to becoming infected upon exposure -- cervial ectopy (endometrial lining comes out and covers the front of the cervix- in vagina, bacteria can attach here more easily) -- decreased local immunity in genital tract -- a smaller nitrites and/ or lack of lubrication can lead to traumatic sex - in males increased STI susceptibility occurs in uncircumcised males regardless of age --phimosis
70
sexual health inequalities
Disproportionately affects those experiencing poverty and social exclusion. Most prevalent in: - Asylum seekers and refugees - Sex workers and their clients - Homeless and young people in and/or leaving care. - Men who have sex with men - Some black & minority ethnic groups - Young people.
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sensitivity of a test
sensitivity is the proportion of people with disease who will have a positive result
72
specificity of a test
specificity is the proportion of people without the disease who will have a negative result
73
what does sensitivity and specificity
High sensitivity is good for ‘ruling out’ a disease if a person tests negative Mnemonic SnNout (high Sensitivity, Negative test = rule out) High specificity is useful for ‘ruling in’ a disease if a person tests positive Mnemonic SpPin (high Specificity, Positive test = rule in) Positive predictive value (PPV) is proportion of people with a positive test who actually have the disease. PPV = a/(a+b) = 0.62 or 62% Negative predictive value (NPV) is proportion of people with a negative test who do not have the disease. NPV = d/(c+d) = 0.98 or 98% Diagnostic results need to be considered in parallel with history and clinical assessment
74
Chlamydia trachomatis
C. trachomatis is an obligate intracellular parasite Small Gram-negative bacilli with no peptidoglycan layer in cell wall Serovars D – K primarily associated with urogenital infections Vertical transmission between mother & baby possible (conjunctivitis/pneumonia) Serovars L1, L2, L2a & L3 associated with Lymphogranulosum venereum (LGV) When pregnant will do tests so that they can be treated, can be passed from mother to baby during child birth and could also contribute to miscarriages and complications C. trachomatis exists in two forms: Elementary body (infective form) Reticulate body (non-infectious form) Chlamydia trachomatis elementary bodies infect columnar epithelial cells. The incubation period until clinical symptoms is around 1 – 3 weeks
75
Clinical presentations of C. trachomatis
Majority are asymptomatic 50% of infected males 80% of infected females Infection may cause a mucopurulent cervicitis in females and urethritis in males Ascending infection can result in pelvic inflammatory disease (PID) in women 5-10% of PID women develop perihepatitis (Fitz-Hugh-Curtis syndrome) Ascending infection can result in epididymitis in men. PID- can c cause issues with reproduction
76
Complications of untreated C. trachomatis
females 10-40% will develop PID A significant proportion of cases are asymptomatic Symptoms can include: Vaginal discharge Lower abdominal pain (dull, aching, crampy, bilateral, and constant) worsened by motion, exercise or intercourse PID can result increase risk of infertility, ectopic pregnancy and chronic pelvic pain males Epididymitis which may reduce fertility or sterility Prostatitis Urethritis causing painful urination and possible kidney problems
77
Diagnosis of Chlamydia
urethral swab rectal swab cervical swab midstream urine McCoy, Hep-2 or HeLa cell lines treated with cycloheximide (50 – 85% sensitivity; 100% specificity) Nucleic acid amplification test (85 - 95% sensitivity; 99 - 100% specificity) - this is cheaper and faster normally will just treat best guess before test results are back
78
nucleic acid detection of bacteria in human sample
- obtain human sample for testing - lyse bacterial cells to access ribosomal RNA (rRNA) - wash lysate over beads coated with DNA that will hybridise to rRNA of interest - pull down beads, isolating rRNA of interest - made double-stranded DNA (dsDNA) copy of rRNA -transcription mediated amplification of dsDNA into millions of RNA molecules - hybridise RNA molecules with fluorescent DNA probe, quantify fluorescence
79
Treatment of Chlamydia-positive patients (prior to 2018)
Prefer a single dose treatment (compliance) First line until 2018 was 1g single oral dose of azithromycin However guidelines have changed in response to: Mycoplasma genitalium co-infection in 3- 15% of cases (high incidence of macrolide resistance) Concomitant rectal infections in women with urogenital infection, not related to anal intercourse (contribute to re-infection rates)
80
Treatment of Chlamydia-positive patients
Uncomplicated urogenital infection: Doxycycline 100mg bd for seven days (contraindicated in pregnancy) Azithromycin 1g orally as a single dose, followed by 500mg once daily for another two days (3 days total) Alternative options: Erythromycin 500mg BD for 10 – 14 days Ofloxacin 200mg BD (or 400mg OD) for 7 days (CI in pregnancy) LGV - Doxycycline 100mg BD for 21 days Abstain from all forms of sex during treatment Contact tracing to minimise transmission
81
Update: the promise of an effective chlamydia vaccine
Used a major outer membrane protein (CTH522) as the antigen 3 x IM injections of vaccine at 0, 1 and 4 months followed by 2 x intranasal boosters at 4.5 and 5 months IM: 85mcg CTH522 liposomal adjuvant CAF01 (625 µg N,Nʹ-dimethyl-N,Nʹdioctadecylammonium [DDA] stabilised with 125 µg of the synthetic mycobacterial immunomodulator α,αʹtrehalose-6,6ʹ-dibehenate [TDB]) IN: 30mcg CTH522 (no adjuvant) 3 x IM followed by 2 x intranasal boosters Vaginal antibody responses (IgA & IgG secretion) – humoral immunity Interferon g production - cell mediated immunity
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Neisseria gonorrhoeae
N. gonorrhoeae is a Gram-negative intracellular, aerobic diplococcus Female to male transmission is ~ 20% per vaginal intercourse episode (60 – 80% after 4 exposures) Mucopurulent urethritis most common presentation (> 80%), 50% dysuria (some may be symptomless) Male to female transmission is ~ 50 – 70% after vaginal intercourse Includes vaginal discharge (≤ 50%), dysuria (10%), dyspareunia and mild lower abdominal pain (≤ 25%) (some may be symptomless) Rectal infections ~ 40% female (similar in MSM) Pharyngeal infections ~ 15% (oral sex – fellatio > cunnilingus) Incubation period typically 1 – 14 days
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Neisseria gonorrhoeae
Deposited on mucous membranes during sexual activity (endocervix, urethral, anus, pharynx). Attachment of bacteria using fimbrae to microvillus on non-ciliated columnar epithelial cells. Bacteria gain cellular entry by parasite-directed endocytosis. Bacteria transported to basement membrane and released by exocytosis where they multiply in the subepithelial tissue. This results in various inflammatory cells being recruited and various factors released Cellular damage and inflammatory exudate accumulates in lumen.
84
Gonorrhoea diagnosis and treatment
Primary diagnosis by NAAT Sensitivity > 96%; specificity 99 – 100%) Culture swabs for diagnosis and/or resistance profiling on Thayer-Martin plates Sensitivity: 90 – 95% for males and 50 – 75% for females; specificity 100%) Treatment of uncomplicated anogenital and pharyngeal infections: 1g ceftriaxone IM as single dose (if susceptibility unknown) 500mg ciprofloxacin as a single dose (if susceptibility known) Test of cure in all patients recommended Abstain from all forms of sex for 7 days
85
Alternative regimes for gonorrhoea
Cefixime 400mg orally as a single dose plus azithromycin 2g orally Only advisable if an intramuscular injection is contraindicated or refused by the patient. Resistance to cefixime is currently low in the UK. Gentamicin 240mg intramuscularly as a single dose plus azithromycin 2g orally Spectinomycin (unlicensed) 2g intramuscularly as a single dose plus azithromycin 2g orally Spectinomycin is not recommended for pharyngeal infection because of poor efficacy. Azithromycin 2g as a single oral dose – relapse risk high The clinical efficacy of azithromycin does not always correlate with in vitro susceptibility testing and azithromycin resistance is high
86
Anogenital warts (condyloma)
Caused by human papilloma viruses Around 30 associated with anogenital infections > 90% of anogenital warts caused by HPV 6 & 11 These types have low oncogenicity Spread by skin to skin contact (penetrative sex not a prerequisite) or indirect e.g. sex toys. Present on: Genitals Groin region Anus Prevalence 30 – 50% population Transmission rates M2F 55%; F2M 70% @ 3months Incubation period – months to years
87
Treatment for anogenital warts
Restricted to external visible warts If less than 4cm2 skin surface involved then home treatment with topical podophyllotoxin Four treatment cycles consist of BD application for 3 days followed by 4 days rest 30 – 70% response rate at 4 -6 weeks but recurrence common Imiquimod for refractory cases (3 x week for up to 16 weeks) Recurrence less common Alternatives cryotherapy or electrocautery
88
Anogenital herpes
Caused by HSV-1 or -2 Transmission by skin to skin contact (penetrative sex not required) or indirect e.g. sex toys 80% of people infected may experience no or such mild symptoms they remain undiagnosed 50% of population will have HSV-1 by age 30 3 – 10% of population will have HSV-2 (up to 25% of sexually active persons) Incubation period may be 4 – 14 days or even longer
89
Diagnosis & treatment for anogenital herpes
Primary infection may be characterised by flu-like symptoms and small blisters that burst to leave red open sores (up to 20 days duration) Can include genitals, rectum, cervix, buttocks or thighs Urinating can be painful Diagnosis by sampling blister - PCR Treatment with 400mg acyclovir TDS for 5 days HSV-1 50% chance of at least one recurrence HSV-2 80% chance of at least one recurrence Frequency/severity of recurrence diminishes with time
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reasons for sterilising products
Medical or surgical procedures often breach the protective barriers of the host e.g. skin and mucosal surfaces or are topically applied to important body structures e.g. eyes, ears. Critical that the pharmaceutical or surgical products being used are sterile to prevent the exposure of host tissue to potentially harmful microorganisms
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examples of sterile products
pharmaceuticals : Parenteral injections & infusions, ophthalmic preparations, ear preparations, wound and bladder irrigations surgical: Wound dressings, artificial joints, cardiac pacemakers, surgical instruments, surgical gloves, hypodermic needles
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what is a sterile product
From an academic perspective the concept of sterility is absolute complete absence of viable microorganisms from a product From a Pharmacopoeial perspective the tests to establish sterility are often limited to the grounds of statistical probability due to limitations in the testing criteria available
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what does a sterilisation process achieve
Sterilisation refers to the process of removing or killing microorganisms from the product to render it sterile A number of sterilisation methods are presently used: Heat (steam & dry heat) Radiation (e.g. gamma-rays or high energy electrons) Gaseous (e.g. ethylene oxide or formaldehyde) Filtration (with subsequent aseptic processing) The exact method applied depends upon the physicochemical stability of the product to be sterilised
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Sterilisation process alone should not be relied upon for product quality
All the steps in the manufacturing process contribute to achieving sterility Sterility also depends upon: Microbial burdens of raw materials, equipment and facility The operators The use of validated sterilisation protocols In-process control of the process and the production environment Suitable storage conditions of the finished product to prevent recontamination
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Sterility does not sit in isolation of other product attributes
Parenteral products should: be practically-free from particles (Pharmacopoeial limits) be pyrogen free (Pharmacopoeial limits) be physiological compatible in terms of pH, tonicity Eye drops should be buffered near physiological pH of tears These parameters still need to be considered as part of the overall development process
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Heat Sterilisation
Two methods are routinely used in sterilisation Moist heat (denatures cell wall and cytoplasmic constituents (like proteins) and/or hydrolysis)- more effective Dry heat (denatures by oxidation) The destructive action of heat on viable microorganisms is most pronounced in the presence of moisture The enhanced sensitivity of microorganisms to heat in the presence of moisture allows reduced operating temperatures and times to effect sterilisation
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Heat Sterilisation
Two methods are routinely used in sterilisation Moist heat (denatures cell wall and cytoplasmic constituents (like proteins) and/or hydrolysis)- more effective Dry heat (denatures by oxidation) The destructive action of heat on viable microorganisms is most pronounced in the presence of moisture The enhanced sensitivity of microorganisms to heat in the presence of moisture allows reduced operating temperatures and times to effect sterilisation
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Moist Heat Sterilisation
At normal atmospheric pressure steam would kill most but not all types of microorganism E.g. bacterial spores remain viable even if they are heated for prolonged periods of time Higher steam temperatures are used to ensure that all microorganisms are killed in a product To obtain higher steam temperatures the water must be heated under pressure in an autoclave Steam is merely water in the vapour (gas) phase In order to transform water from the liquid to the vapour state energy must be added to the liquid The energy input bringing about this physical change in phase can be sub-divided into two parts Energy to raise the temperature of the mass of liquid water to its boiling point (4.2kJ/kg/°C) Energy to transform the mass of liquid water at its boiling point to a vapour pressure (referred to as the latent heat of vaporisation = 2220kJ/kg) The exact boiling point of water will be determined by the pressure of the atmosphere in which the water is heated (boiling point will increase with increasing pressure)
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steam
Steam is referred to as being saturated when it is at a temperature corresponding to the liquid boiling point appropriate to its pressure The effectiveness of saturated steam under pressure at destroying microorganisms is intimately related to the physical properties of the steam under pressure that allow the steam to efficiently transfer heat to the product requiring sterilisation When steam comes into contact with an object whose temperature is below the steam’s saturation temperature, the steam condenses into liquid water (at 121°C) on the object and transfers the latent heat of vaporisation (2220kJ/kg) to the object Condensation causes a rapid contraction in volume (~785x ↓) and creates a localised region of low pressure that is filled by additional saturated steam This property ensures the rapid penetration of the load by the steam The process continues until the object reaches the temperature of the surrounding steam Increased pressures are only used to elevate the temperature at which saturated steam is produced The pressure itself has no antimicrobial action Water quality used to produce saturated steam is also important otherwise contamination with chemical residues within water possible If the temperature increases above the saturation-pressure boundary or if the pressure is reduced below the saturation temperature – pressure boundary then steam is referred to as being superheated
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superheated steam
Superheated steam behaves like an ideal gas and is not as lethal to microorganisms as saturated steam
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thermal stages within an autoclave
A- heating up phase B- holding phase (where most microbial kill occurs) C- cooling phase
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applications of moist heat sterilisation
Only products that can withstand the process temperatures and that are not susceptible to moisture damage can be sterilised by saturated steam In practice three categories of product are sterilised Aqueous products Ophthalmic products Large/small volume parenterals These are normally contained in a non-porous container made of glass or thermostable plastic Saturated steam does not have to come into direct contact with the product as the water content in the product will itself ensure inactivation of microorganisms as long as it is maintained at the sterilisation temperature
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non porous loads
Items such as surgical instruments, rubber closures for vials or items used in the production of sterile products e.g. Rubber tubing for transfer of sterile solutions or stainless steel mixing blades for mixers Products usually wrapped into special containers that allow the penetration of saturated steam during the sterilisation process and prevent the ingress of microorganisms after the sterilisation process is complete Porous loads Porous materials that would be routinely sterilised include wound dressing and filters
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dry heat sterilisation
It is performed in a hot air oven Poor heat transfer capacity of air lead to prolonged sterilisation cycles at higher temperatures than moist heat Heat is provided by electrical heating elements placed around the internal insulated chamber wall Fans within the oven ensure that air is evenly distributed throughout the oven to prevent temperature gradients within the oven Heat is transferred to the products by conduction, convection and radiation Variables such as the size and distribution of the load can influence heat transfer and performance of the oven
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applications of dry heat sterilisation
Used to sterilise a variety of thermostable products that are moisture sensitive Ophthalmic ointments Oil, wax and fat excipients that are used in the manufacture of sterile oily (depot) injections, implants or ointments Powders used in the manufacture of sterile suspensions or powders Depyrogenation of glassware Temperatures > 220°C are routinely used to sterilise and destroy bacterial endotoxins on glassware BP requires 3-log10 reduction in endotoxin(super potent)
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Radiation sterilisation
Only high energy g-rays and high energy electron beams are used to sterilise products The introduction of radiation as a sterilising technique only became widespread after the development of the nuclear industry Allowed the main isotope Co-60 to become available in sufficient quantities Co-60 decays in a single step process to produce Ni-60 Co-60 -> Ni-60 + 2g-rays + b The total energy of the g-rays and electron released from the Co-60 is 2.81MeV which is equivalent to 4.4 x 10-13J The energies of the two g-rays allow them to penetrate through most products Penetrate into a product with a density of water to a depth of 30cm The BP recommends that a product receives a dose of 25kGy (2.5 x 104 J/kg) to achieve terminal sterilisation gamma rays can damage API or container
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radiation continued
The energy from the g-rays is small compared to the energy input provided by moist or dry heat methods of sterilisation However the energy delivered by an individual g-ray is highly localised as it penetrates through the product The g-ray has sufficient energy to break covalent bonds found between atoms in organic macromolecules Carbon-carbon bond is broken by an energy input of 5.77 x 10-19J The alteration in the chemical composition of important macromolecules induced by the g-rays results in the death of the microorganism (May also denature product)
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Applications of radioactive sterilisation
Gamma-radiation has found widest use in the sterilisation of medical devices such as prosthetics, catheters, disposable plastic syringes and surgical clothing It has also been used as a ‘cold’ sterilisation process for heat sensitive pharmaceuticals such as monoclonal antibodies, enzymes and peptides in addition to certain product containers
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Applications of radioactive sterilisation
Gamma-radiation has found widest use in the sterilisation of medical devices such as prosthetics, catheters, disposable plastic syringes and surgical clothing It has also been used as a ‘cold’ sterilisation process for heat sensitive pharmaceuticals such as monoclonal antibodies, enzymes and peptides in addition to certain product containers
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Gaseous Sterilisation
A number of chemicals have been used as gaseous sterilants Ethylene oxide- carcinogen, explosive – used in industry Formaldehyde Peracetic acid- use in hospitals- not as toxic Hydrogen peroxide- use in hospitals- not as toxic Vast majority of gaseous sterilisation operations are performed with ethylene oxide
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Sterilisation with ethylene oxide
Ethylene oxide is a colourless, practically odourless cyclic ether with a boiling point of 10.7°C at atmospheric pressure In its pure form ethylene oxide is explosive and highly flammable with air To reduce the risk of explosion the ethylene oxide is commonly mixed with an inert gas such as carbon dioxide or dichlorodifluoromethane
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ethylene oxide mechanism of action
Ethylene oxide chemically alkylates a range of chemical functional groups present within the microorganisms Will react with other biological structures
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Sterilisation Cycles
A number of parameters impact upon effectiveness of sterilisation cycle Gas concentration (500 – 800 mg/L) Process temperature (40 - 60°C, typically 55 - 60°C) RH ( 40 – 80%, most important parameter) Process times of between 3 - 36hrs are typical
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applications of ethylene oxide sterilisation
Mainly used to sterilise wound dressing, prosthesis and intravenous sets Incapable of sterilising aqueous solutions or gas impermeable products Ethylene oxide is less reliable than other sterilisation methods and should only be used when other methods are not available or applicable
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filtration sterilisation
The technique of filtration can be defined as the separation of an insoluble solid from a liquid or gas by means of a porous medium (the filter) that retains the solid but allows the passage of liquid or gas When the insoluble material is a microorganism suspended either in a liquid or gas then removal of the microorganisms by filtration results in a sterile liquid or gas The mechanism by which filtration mediates sterilisation is fundamentally different to the other methods of sterilisation Sterilisation by filtration is not by definition a terminal process since the resulting sterile solution obtained must be filled and sealed into its final container without the re-introduction of microorganisms Therefore if contamination is to be prevented further processing of the sterile filtrate must be carefully performed under aseptic conditions Aseptic processing requires greater manipulations and is more sensitive to the environmental conditions (microbial bioburden of the facility and product) and dependent on the capabilities of the operators Always choose a terminal sterilisation method if at all possible
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filter composition
Modern filters are made of polymers Cellulose esters (acetate and nitrate) PTFE Nylon Polysulfone- low binding capacity Polymer selection depends upon process conditions e.g. pH, presence of organic solvents, salts
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filter operation
Retention Capture particles that are too large to fit through the membrane apertures (holes or channels) Inertial impaction Particle momentum leads to it embedding/lodging into membrane crevices and dead-ends Adsorptive sequestration Ionic or hydrophobic interactions between particles and membrane polymer Chemistry and process conditions dependent (e.g. pH, salts, solvents)
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Sterilising grade filters have a nominal pore size of 0.2mm
Still allow the passage of certain types of microorganism or metabolites/macromolecules through Viruses (20 - 300nm) Mycoplasma (200 - 300nm) Endotoxin (~ 10-10m) Due to absolute pore size distribution the BP qualifies filter performance in terms of microbial retention Filters will eventually fail if enough microbes are present Mycoplasma- have no cell wall and so can squeeze through small pores in the filter
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membrane microbial retention
The BP states that a sterilising filter must retain a challenge of 107 CFU of Brevundimonas diminuta per cm2 of filter No reference is made to the test conditions under which the filter is challenged So you must qualify every membrane with your product before using to filter sterilise product
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applications of filtration sterilisation
Filtration is primarily used to sterilise solutions that cannot withstand heat treatment It is also used to sterilise gases used in other processes e.g. dry heat sterilisation using hot air Commonly used to filter solutions that are undergoing terminal sterilisation to enhance the microbial quality assurance further
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would a superficial head injury or a deeper head injury bleed more
superficial will bleed much, much more
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head injuries
- did it bleed a lot- superficial - concuss( any vision problem, loss of consciousness or change in behaviour) - head injuries should really be checked out - if a child with regular injuries-safeguarding issue - check any medical condidition/ medications
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burn injuries
- 3rd degree burns- hospital - any medical conditions/ medication - cool water- not freezing cold as this can cause shock - use a moist dressing like paraffin gauze (if dressing is too dry it will rip skin off when healed)
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blister injury
- use a blister plaster like compeed - any medical conditions/ medications -if diabetic any foot injury should get it check regularly
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blister injury
- use a blister plaster like compeed - any medical conditions/ medications -if diabetic any foot injury should be checked regularly
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big graze injury
- hydrocolloid dressing - this will get any dirt or gravel to the surface, may look like puss underneath, this is normal just the dressing - should leave on for as long as possible
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chemical sterilisation indicators
autoclave tape (develops black stripes) Browne's tube (red to green) thermalog strip (yellow to black) problem with these- only rely on one sterilisation parameter (heat)