Cells Flashcards
What can cause urethritis?
Chlamydia trachomatiso
Neisseria gonorrhoeae
Non-specific urethritis: Mycoplasma, Ureaplasma, no organism found
What might be symptoms of vaginal discharge?
Vulval itching and soreness
Creamy discharge
What can cause vaginal discharge?
Gonorrhoea
Chlamydia
Trichomonas
Candidiasis (thrush), Bacterial vaginosis
Both caused by disruption of normal microbiota, not usually considered STI
What might be symptoms of genital herpes?
Painful sores on vulva/ thighs Blisters which burst Very painful dysuria Headache Myalgia
What might be symptoms of primary syphilis?
Painless swelling
Genital ulcers
Systemically well
What can be causes of painful genital ulcers?
Herpes simplex (HSV) 2 and 1 Lymphogranuloma venereum Chlamydia trachomatis Chancroid (rare UK) Non-STI e.g Behçet’s, Stevens-Johnson
What can be causes of painless genital ulcers?
Syphilis Lymphogranuloma venereum Granuloma inguinale Donovanosis- rare UK; Calymmatobacterium Non-STI e.g carcinoma
What are symptoms of pelvic inflammatory disease?
History grumbling lower abdo pain Severe dyspareunia Mild dysuria Fever Discharge Bleeding
What is pelvic inflammatory disease?
Infection upper genital tract
Most commonly STI, but also associated with IUCD (coil), peritonitis
What are signs of pelvic inflammatory disease?
Tenderness incl RUQ, cervical excitation, endocervical pus
What do you need to rule out first before diagnosing pelvic inflammatory disease?
Ectopic pregnancy as may present in same way
What can be complications of pelvic inflammatory disease?
Chronic pelvic pain, tubal infertility, ectopic pregnancy
What may be symptoms of Epididymo-orchitis?
Painful enlarged scrotum
Fever 39C
Ultrasound: no torsion
What are causes of Epididymo-orchitis?
UTI: E. coli commonest
STI: Gonorrhoea, Chlamydia
Viral: mumps
Rare: TB, Brucella
How do you diagnose epididymo-orchitis?
Depends on history Urine for microscopy, culture and sensitivity Urine for STI screen Urethral swab Viral serology
What can be complications of epididymo-orchitis?
Scrotal abscess
Infertility
What can cause genital lumps and bumps?
Genital warts
Molluscum contagiosum
Give some examples of Disseminated manifestations of genital infections
Gonorrheal bacteraemia/ arthritis PID, perihepatitis Secondary and tertiary syphilis Reiter’s syndrome: reactive arthritis secondary to infection Herpes meningitis, encephalitis
Give examples of Systemic disease without genital manifestations
HIV
Hepatitis viruses: A, B, C, (D)
How do you make a microbial diagnosis?
See it (microscopy) Grow it (culture) Kill it (sensitivity)
Detect pathogen: Protein (antigen), Nucleic acid (DNA/RNA)
Detect response to pathogen: Antibody (serology)
What do gonorrhoea look like?
Gram negative diplococci
What technique other than microscopy can be used to diagnose gonorrhoea?
NAAT: nucleic acid amplification test 24-48h to result High sensitivity and specificity Combine with Chlamydia test No antimicrobial susceptibility Requires non-inhibitory specimen (body fluids, including urine may inhibit PCR), not suitable for normal swabs
How can microscopy be used to diagnose gonorrhoea?
Rapid: result in clinic
Less sensitive than NAAT
Requires skilled microscopist
Gives antimicrobial susceptibility result (but 2-3d after clinic visit)
Useful for individual patient treatment, also for epidemiological surveillance
How can chlamydia be diagnosed?
Obligate intracellular bacterium
Will not grow in cell free culture (i.e on an agar plate)
Almost all diagnosis now via NAAT
90-95% sensitivity, >99% specificity
How can syphilis be diagnosed?
Microscopy: dark ground, specific but sensitivity low, Only available
primary syphilis, Skilled technician, Relies on good quality specimen Culture: Treponema pallidum unculturable, Antigen detection using fluorescent antibody, Highly specific if primary lesions present, Higher sensitivity than dark ground
Nucleic acid detection: PCR, High specificity in primary lesions, Not yet in routine clinical use
Serology (antibody detection): Venereal diseases research laboratory (VDRL) antigen, used to be 1st line, Now largely replaced with
simpler, automatable test, Allows diagnosis secondary syphilis
Describe primary syphilis
Single or multiple primary chancres
Usually painless; firm, round
Sore lasts 3-6 weeks with or without treatment
Describe secondary syphilis
Rashes, classically palms and soles
Multiple sores, mucous membranes
Fever, lymphadenopathy, fatigue
Describe latent Syphillis
if secondary untreated
Asymptomatic
Lasts 10-30 years, may progress to tertiary
Describe tertiary syphilis
Tabes dorsalis
GPI (general paralysis of the insane)
Dementia
Argyle Robertson pupils
What are the key points of syphilis diagnosis?
Most diagnoses by antibody detection
Serum: IgM indicates recent infection, IgG stays positive for months/ years/ life
If neurosyphilis suspected may need to test CSF, talk to microbiologist/ reference lab
What is the most commonly diagnosed STI?
Chlamydia
Which STIs increase transmission of blood borne virus STI?
STIs causing inflammation/ open lesions
How can STIs be transmitted?
Sexual contact: Not just genital, Rising incidence extra-genital gonorrhoea
Non-sexual contact: In utero syphilis, Peripartum gonorrhoea,
Chlamydia, Blood-borne BBVs, Other skin/ body fluid: e.g herpes simplex
What are the principles of controlling the spread of STIs?
Remove reservoirs & sources
Interrupt transmission
Increase host resistance
What are methods of primary prevention for STIs?
Safe sexual behaviours
Barrier contraceptive methods
Immunisation: currently only available for HPV (warts)
What are methods of secondary prevention for STIs?
Detect: screening, better access to GUM services, targeted information (16-25s)
If 1 STI, look for others
Prompt effective treatment, contact tracing
How can antibiotics develop resistance?
Efflux
Immunity and bypass
Target modification
Inactivating enzymes
Describe Antibiotic resistance in Neisseria gonorrhoeae
Altered target: resistance to quinolones (ciprofloxacin), resistance to beta-lactams (penicillin-binding proteins), resistance to macrolides (azithromycin)
Drug breakdown: resistance to penicillins
Drug efflux: multiple antibiotic resistance
How is antibiotic resistance spread between strains of gonorrhoeae?
Plasmid and chromosome mediated
Rapid spread between strains
What are the Principles of antimicrobial therapy?
Right drug: For patient and organism. UK guideline on empiric treatment, because susceptibility not known at GUM clinic visit. Check for allergies, contraindications and interactions
Right dose: For patient (weight, liver and renal function), for bacteria (minimum inhibitory concentration)
Right time: Immediately!
Right duration: Single dose effective, increases concordance, minimises side-effects
What symptoms and signs might you get with urethritis? And what behaviours increase the risk of it?
Discharge from penis, staining in pants Pain on passing urine Multiple sexual partners No regular sexual partner No barrier protection
What is the Central dogma of molecular biology?
DNA makes heterogenous nuclear RNA, making messenger RNA, which makes polypeptides, which makes proteins
What determines our phenotype?
Genotype x Environment x Time
Describe classification of genetic disease
Monogentic: Single gene abnormal, Molecular genetic test
Chromosomal: Abnormality of structure or number, Cytogenetics
Multifactorial: Multiple genes and environmental influences, Can perform molecular genetic test to assess risk
What is an allele?
Variant versions of the same genes
What is a Common or wild type allele?
Common in population and NOT associated with a given disease
What is a polymorphism?
Genetic variants that occur commonly in the population with no significant association with disease e.g. blood groups
What are Mendel’s laws of inheritance?
Unit inheritance: Hereditary characters are determined by genes. An allele is one version of a gene
Dominance: Alleles occur in pairs in each indvidual, but effects of one allele may be masked by those of a dominant partner allele Segregation: During formaton of gametes, members of each pair of alleles separate so each gamete carries only one allele of each pair. Allele pairs are restored at fertilisation
Independent assortment: Different genes control different phenotypic characters and alleles of different genes re-assort independently of one another
What are exceptions to Mendels laws?
Sex-related effects: abnormalities inherited on X or Y chromosome
Mitochondrial inheritance: mitochondrial DNA always from mother
Genetic linkage: combinations of some alleles of different genes tend to be inherited together
Polygenic conditions: phenotype reflects actions of multiple genes and
environment, characteristics represent a continuim e.g. height
Overdominance: homozygotes for a given disease allele are distinguishable from heterozygotes, often homozygosity incompatible with life
Incomplete dominance: allele is only dominent in a certain situation Codominance: both alleles expressed in individual e.g. blood group
Variable expressivity: expression of genes modified by other genes and
enviroment so there may be different severities of disease
Incomplete penetrance: dominant allele not phenotypically expressed, due to negation from another factor
Genomic imprinting: mutant alleles confer different phenotypes depending on parent of origin
Dynamic mutation: genetic diseases present with increasing severity in
consecutive generations, due to expansion of a three-base repeat in their DNA
What are Principles of autosomal dominant (AD) inheritance?
Dominant alleles are expressed when present as single copies
Gain of function in protein coded for by mutant allele
Males and females express allele and can transmit it to all offspring Vertical pattern of inheritance (affected person has affected parent)
Parents unaffected, all children unaffected (unless new mutation)
Dominant alleles occur at low frequency as carriers less healthy than genetically normal homozygotes
Significant gene product usually NOT enzymic i.e. structural or a signalling molecule
Give examples of diseases inherited autosomal dominant
Familial hypercholesterolaemia Adult polycystic kidney disease (APCKD) Hereditary spherocytosis Familial adenomatous polyposis coli Huntington disease Achondroplasia
Describe types of familial hypercholesterolaemia
No LDLR is produced LDLR synthesis impaired before it reached PM LDLR cannot bind LDL LDLR do not move to coated pits LDLR cannt release bound LDL
What can be Complications to the AD picture of inheritance?
Codominance: neither allele is dominant over the other and both are expressed in heterozygotes e.g. ABO blood grouping
What are principles of autosomal recessive inheritance?
Alleles are expressed when both are mutated
Carriers are heterozygote for mutant allele but phenotypically normal
AR diseases associated with loss of function of proteins
AR conditions common as carriers (heterozygotes), tend to be healthy
Autosomal so male and females are affected
Pattern of expression is horizontal (siblings), with breaks in pedigree
Affected children are often born to unaffected parents
If both parents are affected then ALL of the offspring MUST be affected
