Renal and Genito-urinary system Flashcards

1
Q

kidney and renal tract: What are the functions of the kidney?

A

Filter 180L fluid daily
Clear waste
Balance acid/base

Produce hormones:
Control blood pressure (renin)

Help to make blood (erythropoietin)

Regulate bone health (Ca, P) (vit. D)

selectivity barrier

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2
Q

kidney and renal tract: What is creatine?

A

End product of skeletal muscle catabolism

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3
Q

kidney and renal tract:

A
  1. glomerulus filtration - h2o and solutes move from blood into nephron
  2. tubular reabsorption - useful substances move from the filtrate in the to the blood
  3. tubular secretion - waste and excess substances move from blood into filtrate
  4. water reabsorption - h20 moves from filtrate into blood
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4
Q

kidney and renal tract: What 3 hormones does the kidney make?

A

Vitamin D - kidney hydroxylates to activate

makes erythropoietin - stimulates bone marrow to make red blood cells

makes renin - part of renin/angiotensin system

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5
Q

kidney and renal tract: What are 3 ways the kidney may dysfunction?

A

Salt and water homeostasis
Changes in total body water
Changes in blood pressure
Changes in urine volume or concentration

Excretion of waste products
Uraemia
Acidosis eg lactic acid, ketoacids
Others: Potassium, Phosphate, Uric acid
Clearance of drugs

Humoral disturbance
Anaemia
Renal bone disease - bones go soft
Hypertension

Barrier failure

  • haematuria
  • proteinuria - froth in the test-tube, ben’s Jone’s proteins come out of solution
  • lipiduria
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6
Q

kidney and renal tract: What investigations are done to investigate kidney disease?

A

Blood tests
- measured glomerular filtration rate GFR (between 60 and 100 may have signs of early kidney disease, below 60 is abnormal, below 15 as kidney failure)

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7
Q

kidney and renal tract: What is the classification of chronic kidney disease?

A

1 Kidney damage (structural/urinary/other)
and Normal GFR >90

2 Mildly reduced renal function 60-89

3 Moderately reduced renal function 30-59

4 Severely reduced renal function 15-29

5 Very severe to End-stage Kidney Failure <15
May require dialysis/transplantation

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8
Q

kidney and renal tract:What are the problems with kidney disease?

A

high blood pressure - beta blockers, ACE inhibitors, calcium channel blockers

anaemia -

bone problems - osteoporosis, renal bone disease, rickets

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9
Q

kidney and renal tract: What is nephrotic syndrome?

A

3 things

Heavy proteinuria
(>3.5g/24hrs or >350mg/mmol uPCR)
Low albumin (<30g/L) (normal 35-50g/L)
Peripheral Oedema

possibly…
Thrombosis – DVT, PTE
Hyperlipidaemia

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10
Q

kidney and renal tract: How is mild/moderate chronic kidney disease treated?

A

Diet/Fluid balance
Supplements- Alkali, Vitamin D, Iron
Drugs – Phosphate, Hypertension, Anaemia

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11
Q

kidney and renal tract: how is severe chronic kidney disease treated?

A

Dialysis

Transplantation

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12
Q

kidney and renal tract: how does dialysis work?

A

take blood from the patient, pass it through a dialysis machine to purify and put it back through again

catheter into the jugular or subclavian vein
risk of infection/sepsis, fistula is made

dialysis membrane is semi permeable and fluid sent in a counter current way

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13
Q

kidney and renal tract: What are the top 5 causes of kidney disease in the UK 2005?

A
Glomerulonephritis - glomerular disease
pyelonephritis - tubular disease
diabetes 
polycystic kidney disease
hypertension/renovascular disease (problem of atherosclerosis)
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14
Q

kidney and renal tract: What are the complications of people with end stage renal failure?

A

CVD - hypertension, K related arrhythmias, cardiac valvular calcifications

infections
malnutrition
immunocompromised
renal osteodystrophy

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15
Q

kidney and renal tract: What are the complications of kidney transplant?

A

Immunosuppression but leads to:

  • Infection (atypicals) - oral thrush is common, gingival overgrowth (cyclosporin, calcium channel blockers - amylodopine etc)
  • Cancer (skin, post Tx lymphoproliferative (EBV))
  • Hypertension, Diabetes,

Cardiovascular disease
Recurrent disease

at 5 years - 70% of kidneys still working

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16
Q

Pathology of renal disease: How much fluid do your kidneys filter and reabsorbs per day?

A

180 litres per day

reabsorbs 178 litres per day

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17
Q

Pathology of renal disease: Why may there not be enough filtration?

A

Not enough blood flow - acute

Blocked filter (minimal change, membraneous blockage (proteins blocking), cells blocking (proliferative) - acute

lack of glomeruli - over years and can lead to chronic hypertension

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18
Q

Pathology of renal disease: Why may there be too much filtration?

A

Leaky membranes - pores are bigger than they should be so bigger molecules like albumin can get through e.g. proteinuria - acute

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19
Q

Pathology of renal disease: Why may there be too little reabsorption?

A

faulty tubules - pass too much urine

causes of tubule dysfunction - lack of blood supply so g et acute tubular necrosis - too much urine produced, cannot reabsorb, but tubules can regenerate

and because of toxins, myoglobin, ethylene glycol

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20
Q

Pathology of renal disease: why may you get blocked/inflamed tubules?

A

neutrophil casts?
crystals/calcification blocking
blood clots

bacteria, neutrophils, macrophages?

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21
Q

Pathology of renal disease: Why may tubules die off?

A

Pyelonephritis
papillary necrosis
tumours can develop - renal cell carcinoma (pain in loin, or blood in urine)

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22
Q

Pathology of renal disease: What are the risk factors for renal cell carcinoma?

A

obesity
cigarette
von hippel Lindau syndrome
acquired renal cystic disease (dialysis)

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23
Q

Pathology of renal disease: what is the treatment of RCC?

A

Surgical resection, radiotherapy

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24
Q

Pathology of renal disease: Where does RCC spread?

A

Direct, lymphatic, peritoneum, blood/bone

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25
Pathology of renal disease: What are the risk factors for transitional cell carcinoma of the renal pelvis?
cigarette smoking industrial dyes e.g. aniline long term painkillers
26
Human herpesviruses: What is the structure of the herpes virus?
Small virus 120-200 nm Icosahedral (viral shape) capsid surrounding ds (double stranded)DNA 80 genes coding for ~ 100 proteins
27
Human herpesviruses: how do you classify human herpes viruses classification?
α-herpesviruses - epidermal/neuronal viruses with a wide host range Type 1 Herpes Simplex Virus Type 2 Herpes Simplex Virus Varicella-Zoster Virus (VZV) HHV-1 HHV-2 HHV-3 β-herpesviruses - slow growth, primarily in T-cells and leukocytes Cytomegalovirus (HCMV) Human Herpesvirus 6 Human Herpesvirus 7 γ-herpesviruses - primarily B-lymphocytes Epstein-Barr virus (EBV) Human Herpesvirus 8 HHV-5 HHV-6 HHV-7 HHV-4 HHV-8
28
Human herpesviruses: What diseases are caused by herpes virus?
check slides
29
Human herpesviruses: How does the herpes virus infect and replicate?
virus binds to host receptor - binds to glycoproteins, then receptor taken inside cell dna released from virus particle - (uncoated) translocates to the nucleus viral dna in the nucleus interacts with host polymerases Transcription occurs - mrna of viral protein, gets translated then, viral proteins produced viral protein binds to host polymerase - makes it more efficient machinery replicates viral dna - lots of copies everything is assembled - translocates to nucleus to get packaged to make new viral particles host cell membrane bursts and releases viral particles to infect other cells lots of cell damage occurs
30
Human herpesviruses: Where does HSV1 and HSV2 infect?
HSV 1 n Mainly Oral Infections HSV 2 n Mainly Genital Infections 1° Herpes Simplex (infection) n also called Herpetic Gingivostomatitis 2° Herpes Simplex (reactivation) n Herpes Labialis (cold sores)
31
Human herpesviruses: Where does hSV1virus enter?
Virus enters trigeminal sensory neurones Migrates to trigeminal ganglion Becomes Latent in the Trigeminal Ganglion In 50% of cases it remains dormant in the trigeminal ganglion
32
Human herpesviruses: How does hsv1 get reactivated - becomes secondary infection?
In 50% of cases it becomes reactivated Migrates to peripheral nerve endings Where active viral particles are shed
33
Human herpesviruses: What is secondary herpes infection caused by?
``` Reactivation caused by: n UV light Stress n Illness n Immuno-suppression ``` also causes herpes labialise - cold sores - Lesion resolves Virus lays dormant again in trigeminal ganglion until reactivated
34
Human herpesviruses: What are the clinical features of primary hsv infection?
Incubation period around 5 days Drinking and eating painful, often bad breath (halitosis) Multiple oral vesicles - rupture to form extensive sloughing ulcers Gingivitis with erythema (increased redness of the gums) Malaise, pyrexia (temperature), lymphadenopathy (enlarged lymph nodes) Duration 5-14 days
35
Human herpesviruses: How do you diagnose a primary hsv infection?
Typical clinical appearance | Main diagnostic difficulty with erythema multiforme
36
Human herpesviruses: How do you investigate a primary hsv infection?
Not normally done Rising antibody titre / presence of IgM antibodies Viral culture or now mainly PCR
37
Human herpesviruses: How is PCR carried out?
Denature DNA to single strands - 95 degrees Annealing of specific primers to DNA Extension by polymerase - 55 degrees, then 72 degrees Repeat 30-35 times
38
Human herpesviruses: What is the management for hsv 1?
Acyclovir (200mg 5 x daily for 5 days) if found early or in immunocompromised - must apply when tingling lips Fluids and soft diet Analgesics / antipyretics (paracetamol) Local antiseptics e.g. chlorhexidine Topical analgesics e.g. Difflam X-infection control
39
Human herpesviruses: How does acyclovir work?
HSV thymidine kinase (TK) is more effective at phosphorylating nucleotides than human TK. TK used to make bases for DNA ie viral DNA replication ACV is a false nucleotide. Human cells cannot phosphorylate ACV very well In HSV-infected cells, ACV is phosphorylated by the viral TK enzyme to ACV- P ACV- P then inhibits virus replication – i) Get incorporated into replicating viral DNA but further bases cannot be added as ACV- P lack a terminal hydroxyl group. It is a chain terminator. ii) ACV- P acts on the virus DNA complex and inhibits the activity of DNA polymerase, so virus DNA manufacture is markedly inhibited.
40
Human herpesviruses: What are the clinical features of HSV 2?
Prodromal irritation Vesicles at or near mucocutaneous junction of lips Crusting lesions lasting 7-10 days Usually re-occurs at the same sites Rarely: - may occur, intra-orally, in nose or elsewhere on ski
41
Human herpesviruses: What is the management for hSV2?
Management: Acyclovir cream 5% if used very early OTC drying and antibacterial agents Prophylactic treatment: Rarely justified Prophylactic acyclovir will prevent lesions in the immunocompromised or those susceptible to erythema multiforme
42
Human herpesviruses: What is herpetic whitlow?
Herpetic infection of the fingers from handling the oral tissues of someone with active 1° or 2° Herpes simplex lesions (mainly dentists) Very painful Very difficult to treat Prevention better than cure - wear gloves
43
Human herpesviruses: What is herpetic encephalitis?
Mainly affects frontal lobes of the brain 70% - 80% mortality if untreated Of survivors, only 3% return to normal Usually only people >50 years (HSV-1) and neonates (HSV-2) affected.
44
Human herpesviruses: What are the symptoms of HSV encephalitis in adults?
Adults (HSV-1) • Headache and behavioural changes over several days • Fever • only 11% of cases have a history of recurrent HSV infection
45
Human herpesviruses: What are the symptoms of HSV 2 encephalitis in neonates?
Neonates (HSV-2) • Skin rash, lesions and CNS symptoms • Virus present in liver, lung and adrenal glands • Respiratory distress • Fits and convulsions • Raised intracranial pressure • Incidence is approximately one case per 300,000 live births in the UK
46
Human herpesviruses: What Is the primary and secondary infection of HHV-3?
Chicken pox - varicella zoster virus secondary - herpes zoster (shingles)
47
Human herpesviruses: Where does varicella lay dormant?
In the dorsal root/ trigeminal ganglia
48
Human herpesviruses: Why does HHV3/varicella reactivate?
Age (70% >50yrs) • Stress • Illness • Immunosuppression leads to secondary hsv - shingles, but seldom reoccurs
49
Human herpesviruses: Where does a shingles rash classically appear?
chest and back belt like rash - zoster
50
Human herpesviruses: What are the 3 phases of the herpes zoster virus?
Pre-herpetic neuralgia Rash Post-herpetic neuralgia
51
Human herpesviruses: What are the features of the pre-herpatic neuralgia phase?
Pain in the distribution of the affected division of the trigeminal nerve Prior to the development of the rash May mimic dental pain
52
Human herpesviruses: What are the features of the rash phase?
``` Unilateral vesicles in the distribution of a branch of the trigeminal nerve n Ophthalmic n Maxillary n Mandibular ``` Vesicles break down to form n Ulcers (mucosa) n Crusting lesions (skin) Last 2-3 weeks
53
Human herpesviruses: What optical problems can be caused by Zoster?
glaucoma, cataract, double vision and scaring of the cornea
54
Human herpesviruses: How is herpes zoster managed?
Acyclovir 800mg 5 x daily for 7 days if seen soon after lesions develop Analgesics Ophthalmic referral if eye involved Avoid contact with children
55
Human herpesviruses: What are the new alternatives to acyclovir?
Valaciclovir 1g 3 x daily for 7 days Famiciclovir 250mg 3 x daily for 7 days bit more specific
56
Human herpesviruses: What are the features of the post-herpatic neuralgia phase?
10% of patients go on to get extremely unpleasant intractable burning pain in the distribution of the affected nerve More common in the elderly Effective early treatment of zoster may ↓ risk of neuralgia Treat pain with tricyclic anti-depressants and neuropathic pain drugs
57
Human herpesviruses: What is EBV associated with?
Infectious Mononucleosis (Glandular Fever) – acute 1o infection with EBV Burkitt’s Lymphoma – a B-cell malignancy Nasopharyngeal Carcinoma – an epithelial cell malignancy Oral Hairy Leukoplakia – seen i
58
Human herpesviruses: Where does primary EBV replicate?
oro- pharyngeal epithelial cells but then establishes latency in B-lymphocytes
59
Human herpesviruses: What are the symptoms of ebV?
Symptoms include sore throat, swollen cervical lymph nodes and mild fever Petechiae on soft palate Creamy exudates on fauces Cervical lymphadenopathy Infections in the western world are usually seen in young adults
60
Human herpesviruses: What is Burkitt's lymphoma?
EBV gets into B cells - causes malignant B cell lymphoma treatment - cyclophosphamide (chemo)
61
Human herpesviruses: What happens to immunocompromised people that are infected with hHV-5?
Large ragged oral mucosal ulcers Salivary gland swelling Retinitis
62
Human herpesviruses: What is Kaposi's sarcoma?
lesions all over the body driven by HSV in aids patients
63
Genito-urinary infections: What is the main defence to a UTI?
urination
64
Genito-urinary infections: Where does the infection usually ascend from?
External site up the UT continuum which can lead to involvement of the kidneys
65
Genito-urinary infections: What is a common route of infection of a UTI?
catheterisation
66
Genito-urinary infections: Why are females more likely to get UTI's?
Shorter ureter and nearer to anus pregnancy - pressure on bladde reduces ability to empty bladder and some immunosuppression so higher chance of UTI
67
Genito-urinary infections: What is dysuria and pyuria?
Painful urination urine that contains pus
68
Genito-urinary infections: What is pyelonephritis?
kidney infection, characterised by fever and back pain
69
Genito-urinary infections: What is urethritis and cystitis?
Urethra infection bladder infection
70
Genito-urinary infections:What host factors contribute to getting a UTI?
``` Renal calculi ureteric reflux tumours bladder stones pregnancy neurologic problems prostatic hypertrophy short urethra catherisation ```
71
Genito-urinary infections: What bacterial factors contribute to getting a UTI?
``` capsular antigens hemolysins urease - raises pH so it can grow adhesion to uroepithelium introital colonisation ```
72
Genito-urinary infections:What are the steps to diagnose a UTI?
Sampling of midstream Urine (with care) - cloudy or clear - haematuria? (urine might be pink) culture on agar plates > 2x105 cells/ml *around 500 on a plate) - traces of protein, leukocytes >10/ml - Raised nitrites (NO3- > NO2-)- from bacterial metabolism Pure or mixed growth? - Gram Stain of isolated bacteria or direct staining from urine sample
73
Genito-urinary infections:What is the main organism to cause a UTI?
E coli - gram negative rod Proteus mirabilis- Gram negative pleomorphic rod- swarming motility Staphylococcus saprophyticus- Gram positive coccus
74
Genito-urinary infections: What media do you use to culture UTI bacteria?
Cysteine-lactose-electrolyte-deficient (CLED) media (turquoise coloured) rich media containing lactose and lacking electrolytes (salt) to repress swarming Subsequent plating on Macconkey agar if E.coli suspected (although Gram stain informative). - produces pink colonies then strain designation by PCR and sequencing
75
Genito-urinary infections:What are the features of E coli (UPEC)?
Gram-negative motile bacillus - Also causes GI-infections, but UTIs commonly caused by specific strains of E.coli known as UPEC - These differ at the genome level from enteric strains by having up to 1000 extra genes - Possesses potent adhesins for attachment to epithelium - pili
76
Genito-urinary infections: What two types of pili do UPEC have?
Type 1 pili - Binds mannose receptors, common on glycoproteins in uroepithelium P-fimbriae: (often found in pyelonephritis strains) Binds to globobiose (aD-Gal-(1,4)-aD-Gal) made up of linked ceramide host lipids
77
Genito-urinary infections: Why do you need to track strains of UPEC?
for antibiotic resistance
78
Genito-urinary infections: What does swarming mean?
ability to move over a surface
79
Genito-urinary infections: Which organism can swarm over catheter surfaces?
Proteus?
80
Genito-urinary infections: What are the viruelence factors for proteus?
Urease: urea>> ammonia + CO2, raises pH of urine>>> can cause precipitation of minerals to form kidney and bladder stones IgA protease- reduces flushing… Many pili adhesins
81
Genito-urinary infections: What are the features of staphylococcus saprophyticus?
Gram positive- cocci Haemagglutinin key to attachment to cells common cause of UTIs in young women Coagulase negative Novobiocin resistant - used in diagnosis Most common in young women
82
Genito-urinary infections: What are the treatments for community UTI?
New guidelines do NOT indicate antibiotic use for uncomplicated lower UTI in Non-Pregnant women Fever, pain in kidney area- antibiotics recommended, in men and pregnant women always indicated > 3-day course in women, 7-day in men (infection is less common, can be more serious by the time detected) Common antibiotics: Nitrofurantoin (1st-line) Ciprofloxacin, penicillins and trimethoprim Resistance a growing issue, esp. for E. coli (>30% are Tm resistant)
83
Genito-urinary infections: How can catheterisation leads to UTI's
Usually skin commensals like S. aureus and epidermidis or Pseudomonas spp. (Strict aerobe), Klebsiella and Enterococcus become opportunistic and a lot of them are resistant ESKAPE pathogens
84
Genito-urinary infections: What are the ESKAPE pathogens?
``` Enterococcus faecium Staphylococcus aureus Klebsiella pneumoniae Acinetobacter baumannii Pseudomonas aruginosa Enterobacter species ```
85
Genito-urinary infections: What is the treatment for UTI in hospitals?
Similar to community but may require IV antibiotics: nitrofurantoin, cefalexin, Penicillins- depends on microbiological data, resistance profiles Immediate removal and changing of catheter and bag Super-resistant E.coli infections now treated with Plazomicin in USA_ expected to come to UK soon.
86
Genito-urinary infections: How are STD's transferred?
Any form of sexual activity in which no barrier is used and exchange of fluid or contact with mucosal epithelium occurs
87
Genito-urinary infections: What are the main organisms causing STI's?
Neisseria gonnorhoea >>> Gonnnorhoea Chlamydia trachomatis >>> chlamydia Treponema pallidum >>> Syphilis
88
Genito-urinary infections: What are the features of N.gonorrhoeae?
Exclusively a fully virulent human pathogen; - never found as a commensal Asymptomatic carrier state: mainly females - Acute urethritis in 95% males - only ~ 50% women show discharge, dysuria Ascend to Fallopian tubes - acute salpingitis (infection of the Fallopian tubes), pelvic inflammatory disease - sterility Ophthalmia neonatorum – infant blindness Oral gonnorhea (bacteria prefers columnar epithelium instead of squamous)– very rare, but can result from oral sex with infected man
89
Genito-urinary infections: What is the pathogenicity of N.gonorrhoeae?
Surface pili- pil proteins- attachment Opa proteins- aid attachment Lipo-ologosaccharide: sialylated (sialic acid is a host sugar)- complement resistance- host mimicry Por proteins- nucleate actin aiding cell invasion Possesses IgA protease- aids survival inside host cells Release into bloodstream disseminates infection to other sites fever, arthiritis (1-3% women, much lower in men), endocarditis
90
Genito-urinary infections: What does infection of N.gonorrhoeae increase the chance of?
Hiv x5 Co-infection of HIV and N. gonorrhoeae increases transmission of HIV by 500% (WHO)
91
Genito-urinary infections: how is gonorrhoea diagnosed?
Urethral swab - Susceptible to dessication, so transport medium used - Sub-culture on chocolate agar - Sugar fermentation tests–glucose +ve - Oxidase test positive
92
Genito-urinary infections:How is gonorrhoea treated?
Contact tracing- antibiotic prophylaxis of contacts Historically penicillin and tetracyclines were drugs of choice Ceftriaxone (IM) and azithromycin - most common (1g orally) recommended first line choice (also kills chlamydia). Many 3rd world strains are Penicillin and Tetracycline resistant, susceptibility tests must be performed
93
Genito-urinary infections: How does syphilis progress?
Initial incubation period (2- 10 weeks) Primary lesion: chancre at site of infection - Resolves spontaneously Secondary syphilis : - 6-8 weeks post-infection, Bacteria disseminate around body - Flu-like illness: myalgia, headache, fever, rashes. Latent syphilis: 3-30 years- no symptoms Tertiary Syphilis: - Neurosyphilis- CNS - CV sequelae- aortic lesions, heart failure - skin and bone deformity Treponema sensitive to long-acting penicillin- easily treatable - slow-growth means long-acting course required.
94
Genito-urinary infections: What organisms causes syphilis?
Treponema pallidum TRANSMISSION: Sexual contact via minute skin abrasions Vertical transmission- cross placental: Congenital syphilis
95
Genito-urinary infections: How does syphilis progress?
check slide 52
96
Genito-urinary infections: how does congenital syphilis occur and how does it present?
Crosses placenta - Can lead to still-birth - Congenital infection - Birth deformities, silent infection – presents as facial and tooth deformities at 2 years of age
97
Genito-urinary infections: What are the features of chlamydia trachoma's?
Often asymptomatic in females 50% symptomatic in males Re-infection common as immunity weak Incubation period 7 – 14 days Disease due to direct damage to cells and immunopathology causing fibrosis and scarring Can also cause conjunctivitis- common co-occurence.
98
Genito-urinary infections: What are the consequences of chlamydia in women?
Asymptomatic infection = 70 % Mucopurulent cervicitis Urethral infection Pelvic inflammatory disease in up to 40% - ascending infection involving uterus, fallopian tubes, and other pelvic structures Complications include chronic pelvic pain, ectopic pregnancy and infertility
99
Genito-urinary infections: What is proctitis?
Inflammation of rectum
100
Genito-urinary infections: What are the features of chlamydia bacteria?
Very small obligate intracellular parasite Small genome Enters through minute abrasions Specialised life-cycle Seems to avoid and not stimulate immune responses (privileged site?) Prefers to infect non-ciliated columnar and cubiodal epithelium: genital tract from urethra up to fallopian tubes and rectum Also respiratory and conjunctival cells
101
Genito-urinary infections: How to diagnose and treat chlamydia?
Tests are available on NHS (and free in Gyms etc): Culture in cells Direct immunofluorescence and ELISA PCR tests (known as NAAT) TREATMENT: Azithromycin (single dose). Doxycycline (longer course).