Session 6 Flashcards
Describe the epididymal maturation of sperm.
Functions of seminal plasma
- On entry to epididymis, spermatozoa not capable of movement
- Once at the tail of the epididymis they are capable of movement and have the potential to fertilise
- Addition of secretory products to surface of sperm
Maturation:
Dependent on support of the epididymis by androgens
Semen consists of Spermatozoa and Seminal plasma
- Seminal plasma derived from accessory glands of the male reproductive tract
- Functions of seminal plasma:
- Transport medium • Nutrition • Buffering capacity • Potential role for prostaglandins in stimulating muscular activity in the female tract
What are the contents of seminal plasma?
Seminal vesicles
- 60% of volume
- alkaline fluid (neutralizes the acid: male urethraand female reproductive tract)
- fructose, prostaglandins, clotting factors (particularly semenogelin)
Prostate gland
- 25% volume
- milky, slightly acidic fluid
- proteolytic enzymes (breakdown clotting proteins, re-liquefying semen in in 10-20 minutes ) • citric acid, acid phosphotase
Bulbourethral glands (Cowper’s glands)
- Very small volume
- alkaline fluid
- a mucous that lubricates the end of the penis and urethral lining.
Normal site of fertilisation?
Fertilisation site is normally ampulla of uterine tube
What are the phases of the human sexual response?
- Excitement phase - Psychogenic and / or somatogenic stimuli
- Plateau phase
- Orgasm phase
- Resolution phase - Return to haemodynamic norm followed by a refractory period in males
Describe how an erection is stimulated
First step in male sexual response (excitement phase) is erection which requires stimulation which can be psychogenic and/or tactile (from sensory afferents of penis and perineum). That gives a spinal reflex and then the efferents are both somatic and autonomic efferents through the pelvic nerve (PNS) and the pudendal nerve (somatic). These lead to the hemodynamic changes which give men an erection
What does an erection require from the penile anatomy?
- Oraganised by Tunica albuginea which surrounds the corpus spingiosum and corpus cavernosa. Relatively rigid.
- Erection requires:
Sinusoidal relaxation and arterial dilation in corpora cavernosa and corpora spongiosum allowing more blood in.
• Venous compression prevents blood leaving and that is achieved by the rigid albuginea.
How does parasympathetic innervation aid in getting an erection?
Parasympathetic innervation
• Fibres in the lumbar and sacral spinal levels conduct through the pelvic nerve and pelvic plexus onwards to the penis through the cavernous nerve to corpora and vasculature
Describe the neurophysiology of erection
Need inhibition of sympathetic arterial vasoconstrictor nerves and activation of PNS
- Activation of non-adrenergic, non-cholinergic, autonomic nerves to arteries, releasing Nitric Oxide (NO)
- Post-ganglionic fibres release ACh
- ACh bonds to M3 receptor on endothelial cells
- A rise in [Ca2+]i , activation of NOS and formation of NO
- NO diffuses into vascular smooth muscle and causes relaxation (vasodilation)
- NO also released directly from nerves
What causes an erectile dysfunction?
- Psychological (descending inhibition of spinal reflexes) causing reduction in NO
- Tears in fibrous tissue of corpora cavernosa so cant retain blood
- Vascular (arterial and venous) e.g from diabetes
- Drugs
Sildenafil/Viagra slows the degradation of cAMP which in turn causes penile erectionas if not broken down , you can maintain nitric oxide presence fo longer.
How is emission and ejaculation carried out in the male sexual response?
This phase is under sympathetic control
Emission • Movement of semen into prostatic urethra • Contraction of smooth muscle in prostate, vas deferens and seminal vesicles
Ejaculation (orgasm) • Expulsion of semen
Occurs through:
- Contraction of glands and ducts (smooth muscle)
- Bladder internal sphincter contracts - Preventing retrograde ejaculation
- Rhythmic striatal muscle contractions (pelvic floor, and perineal muscles ischiocavernosus, bulbospongiosus)
Summarise the autonomic control of male sexual function
Erection
- Sympathetic - Inhibition (reduction of tone at arterioles)
- Parasympathetic • Active
Ejaculation
• Sympathetic • Active • Contraction of ducts
What are the menstrual changes in the female tract?
- The character of cervical mucus changes over the course of the menstrual cycle
- Oestrogen makes mucus thin and stretchy facilitating the movement of motile gametes through the female genital tract
- Once ovulation has occured oestrogen and progesterone togeher make mucus thick and sticky forming a plug, prevents any further access to any more male gametes and if pregnancy occurs then allows a small amount of protection
What’s the difference in site of deposition of sperm and site of fertilisation?
Deposited at external os of cervix but fertilisation most often occurs at ampulla of falopian tube
What is capacitation?
- Further maturation of sperm in female reproductive tract (6-8 hours)
- Sperm cell membrane changes to allow fusion with oocyte cell surface
- Tail movement changes from beat to whip-like action
- Head now capable of undergoing the acrosome reaction
When is the fertile window? How are the gametes transported?
- Spermatozoa 48 -72hr • Oocytes 6 – 24 hr (max)
- Fertile period: sperm deposition up to 3 days prior to ovulation or day of ovulation
- Gamete transport
- Oocyte: beating cilia & peristalsis of uterine tube
- Sperm: own propulsion by its flagellum
Give an overview of the events in fertilisation
- Occurs normally in the ampulla of the uterine tubes
- Requires loss of sperm outer shell (acrosome)
- Penetration of ovum membrane, fusion of ova and sperm membrane. penetration facilitated by whip like motion of the spermatazoa.
- Eventual formation and fusion of pronuclei
What is the role of the acrosome?
- Derived from golgi region of developing spermatid
- Contains enzymes - Necessary for fertilisation
Acrosome reaction
• Sperm pushes through corona radiata (follicular cells) • Binding of sperm surface receptor to glycoprotein on zona pellucida • Triggers acrosome reaction • Digestion of zona pellucida
Fertilisation
• One sperm penetrates leading to fusion of plasma membranes, causes wave of calcium signalling in oocyte which initiates cortical reaction (changes plasma membrane) which prevents polyspermy
How is meiosis II resumed after fertilisation?
- Series of calcium waves are activated following fusion of oocyte and sperm membranes
- Resumption of meiosis II occurs
- Pronuclei move together
- Mitotic spindle forms leading to cleavage resulting in first mitotic division
What is the morula?
Cleavage indicates successful fertilisation and leads to further cell division resulting in a morula. Morula - 16 cells contained in the zona pellucida.
- Each cell in the morula at this stage of development is TOTIPOTENT
- i.e. has the capacity to become any cell type
How can laboratory techniques aid in fertilisation? How can this help with disease diagnosis?
- Oocytes are fertilised in vitro and allowed to divide to the 4- or 8- cell stage
- The morula is then transferred into the uterus
Pre-implantation Genetic Diagnosis (PGD) - a cell can be safely removed from the morula and tested for serious heritable conditions prior to transfer of the embryo into the mother
How does the blastocyst hatch?
- First differentiation into inner and outer cell masses
- Formation of the blastocyst, blastocyst hatches from zona pellucida so no longer constrained - now free to enlarge
- can now interact with uterine surface to implant
Describe implanation and its associated possible issues
- Outer cell mass (trophoblast) interacts with endometrium
- Endometrium controls degree of invasion - At this stage endometrium is well into secretory stage with glands and vessels within endometrium well developed due to presence of oestrogen and progesterone.
- Ectopic implantation - Implantation at sites other than endometrium lined uterine cavity
- Invasion not controlled
- Implantation in lower uterine segment can cause placenta praevia - placenta lies low in the uterus and partially or completely covers the cervix. can cause severe bleeding during pregnancy and delivery. If you have placenta previa, you might bleed throughout your pregnancy
How common are STIs?
Most cases of STIs affect people in the ages of 15 to 24. Chlamydia most common STI . STIs are fairly common especially in the more affected age range.
Risk factors for developing an STI?
“Risky sexual behaviours” ◦ Multiple sexual partners ◦ Not using barrier contraception ◦ Early age first intercourse ◦ Certain sexual practices e.g. anal sex more likely to get infection.
Other association:
◦ Low socio-economic status ◦ Race/ethnicity ◦ Lack of immunisation (Hep B, HPV through sexual contact)
What infections can cause urethral dischrge in men?
Sexually transmitted infections that cause urethral discharge:
Chlamydia: Chlamydia trachomatis
The most common STI in the UK
◦ Obligate intracellular bacterium (lets itself be phagocytosed) ◦ Unique cell wall (gram negative but doesn’t follow the exact criteria of gram negative); inhibits phagolysosome fusion (virulence factor)
Typically asymptomatic in men
◦ Can cause testicular pain, dysuria
◦ May have discharge
Gonorrhoea: Neisseria gonorrhoeae
“Gonococcus” ◦ Gram negative ◦ Diplococci ◦ Unencapsulated, pilated (has projections that help it adhere to mucosal membranes)
90% of men are symptomatic so easier to detect (~50% of women)
Most common cause of male urethral discharge
Causes thick, yellow discharge +/dysuria
Can cause reactive arthritis (infection disseminates to cause painful joints)
Non sexually transmitted infections that cause male urethral discharge:
Non-gonococcal urethritis (NGU)
Inflammation of the urethra caused by anything other than gonorrhoea along with associated discharge
Can be sexually transmitted (common)
◦ Chlamydia trichomatis ◦ Mycoplasma genitalium ◦ Trichomonas vaginalis
Can be ‘pathogen negative’(cant find causative organism) (less common, older men)
Investigations when there’s discharge in men?
Urine sample - use first portion of urine (first catch urine)
◦ Gonorrhoea: Microscopy & culture, nucleic acid amplification tests (NAATs)
◦ Chlamydia: NAATs (most sensitive & specific)
◦ Urethritis: NAATS
◦ Excludes UTI as a cause of dysuria
Urethral swab
◦ Gonorrhoea
Also look at general markers for infection so, temperature, FBC, C reactive protein etc
What can cause vaginal discharge for women?
Could be physiological
Menstrual cycle - Progesterone in the secretory phase (post-ovulation) causes thicker cervical mucus so can casue discharge.
Features of this are: ◦ Cyclical ◦ No other associated symptoms ◦ Clear
Sexually transmitted infections
As per men: (More women are asymptomatic)
◦ N. gonorrhoeae
◦ C. trachomatis (Chlamydia)
Can cause neonal conjunctivitis during prgenancy or delivery
◦ May have discharge
◦ May have postcoital/ intermenstrual bleeding
◦ May have dyspareunia
Trichomoniasis: Trichomonas vaginalis
Protozoa (‘Flagellates’) ◦ Presence of flagella (mobility) ◦ Optimal growth ~ pH 6.0 ◦ Vaginal pH ~4.0 so increased alkalinity of vagina favours acquisition of disease.
Causes copious, yellow, odourous discharge
Can also cause non gonnacoccal urethritis in men
Treatment: Metronidazole
Non-sexually transmitted infections
Candidiasis: Candida sp. (albicans)
Yeast: normal vaginal flora
◦ Activated in immunocompromised states, diabetes
◦ Favours high oestrogen (can be associated with COCP)
VERY ITCHY! ◦ White discharge ◦ Typically non-offensive (odour)
Bacterial vaginosis
Gardnerella vaginalis
Lactobacilli is protective against infection and normal flora of vagina 95%
Altered flora (excessive washing) can cause bacterial proliferation
◦ Increased risk of contracting STIs
Offensive smelling, white discharge
Insert slide 24
What investigations would we use for women with discharge?
If infection is suspected ask about other features of the discharge: Itchy, colour, sexual history and vaginal hygiene?
Can be asymtomatic so screening is important
Risk of pelvic inflammatory disease
Vaginal swabs
Chlamydia: Vulvo-vaginal swabs (VVS), endocervical
Gonorrhoea: VVS, endocervical
Trichomoniasis: High vaginal swab (HVS) (posterior fornix)
Bacterial Vaginosis: Gram staining, KOH test (add drops of potassium hydroxide and positive test will give “fishy smell”)
Candida: HVS; Microscopy > Culture
Urine dip not as effective for detecting STIs in women
What can cause genital lesions in men and women?
Sexually transmitted infections:
Viral: Human Papillomavirus (HPV)
DNA virus (non-enveloped)
Can cause genital or cutaneous warts
Many, many different types!
◦ 6 and 11 cause 90% of genital infections ◦ 16 and 18 have the highest association with cervical cancer
Can do PCR to identify high risk types (biopsy/swab)
Vaccination exists: ◦ Gardasil (6, 11, 16, 18) ◦ Cervarix (just 16 & 18
Viral: Herpes simplex virus (HSV-1 & -2)
DNA virus (enveloped)
Lifelong infection - Initial then recurrent infection
Can be asymptomatic initially, or present with painful ulcers/blisters
◦ Can be accompanied by systemic symptoms
HSV-1: also associated with “cold sores”
HSV-2: more likely to become infected with HIV)
Both vertical and direct transmission
Check all areas ◦ Genitals ◦ Mouth ◦ Anus
Swabs: PCR / NAATs
Management: Antivirals e.g. aciclovir ◦ Cannot eradicate the infection ◦ Reduce the severity and duration of current episode ◦ Limited effect frequency/severity of repeated episodes
Bacterial: Syphilis (Treponema pallidum)
Spirochete - gram-negative, motile, spiral bacteria
More common in men aged 24-35 and homosexual men.
Transmission: ◦ Direct contact ◦ Vertical transmission
Not as common generally ◦ 40% co-infected with HIV
Primary syphilis ◦ Typically painless ulcer(s) Secondary syphilis (25% of untreated primary cases) presents 4 – 10 weeks after initial infection. Can be multi-system. Can enter a latent phase
Identify using microscopy / PCR, Serology
Management: Penicillin-based antibiotics
General management for reproductive tract infections
Sexually transmitted infections
Co-infections are common - Similar route of transmission
May be asymptomatic so consider screening for others
Consider presenting complaint so you can arrange ppropriate investigation & therapy
Bacterial: Can give multiple antibiotics
e.g. azithromycin & ceftriaxone for chlamidia and gonorrhoea.
Targets different organisms
One antibiotic can augment the effect of the other
Patient education
Barrier contraception and other ‘safe sex’ advice
Avoid sex until course of treatment is completed
For non-sexually transmitted infections:
Use appropriate therapy for the organism:
Candida - anti-fungals
BV - antibiotics e.g. metronidazole
Try and remove precipitating feature e.g control diabtes/immunocomprimised state.
Patient education
Advice when taking COCP and vaginal hygiene
What is pelvic inflammatory disease?
Infection of the uterus, fallopian tubes, and ovaries
Typically because of ascending infection:
◦ Chlamydia trachomatis ◦ Neisseria gonorrhoeae ◦ Gardnerella sp. ◦ Others e.g. Mycoplasma genitalium
Often polymicrobial
Other sources of infection: ◦ Intrauterine contraceptives (more to come) ◦ Other uterine interventions
Presentation:
SYMPTOMS
Lower abdominal pain, Dyspareunia, Purulent discharge, Abnormal uterine bleeding ◦ e.g. intermenstrual or postcoital
SIGNS
Pyrexia (+/-), Pain on palpation of abdomen
◦ Examined using bimanual vaginal examination (pain felt during this examination indicates positive test.)
Evidence of discharge/cervicitis (speculum)
PID: Complications
Chronic pelvic pain, pelvic abscess (tubo-ovarian), can lead to subfertility due to adhesions from chronic inflammation ◦ Increased risk of ectopic pregnancy ◦ Reduced likelihood of successful fertilisation
Peritonitis due to further spread
Fitz-Hugh Curtis Syndrome (peri-hepatitis) from spread to capsule of liver. Rare.
PID: Management
Prevention > Cure
Anitibiotics ◦ Give if clinically suspected – don’t delay because of investigations
NB: Negative swabs do not exclude PID
◦ Broad spectrum ◦ IV in more severe cases
Analgesia
Offer screening to sexual partner(s) (genito urinary medicine)
In those who fail to respond to treatment, laparoscopy is essential to confirm the diagnosis or to make an alternative diagnosis.
What are the normal values for semen analysis?
Volume of ejaculate: 2-6 ml
Viscosity: liquefaction in 1hr
pH: 7-8
Count: equal to or more than 20million/ml
Motility: equal to or more than 50%
Morphology: 60% normal
What are the pain differentials for PID?
What are the differentials for abnormal uterine bleeding for PID?
Ectopic pregnancy, inflammatory bowel disease, constipation, cholecystitis, appendicitis, UTI, endometriosis, ovarian cysts
Intermenstrual bleeding, postcoital bleeding, cancer
(use in context with pain, fever and discharge)
