Reproduction - PATHO Flashcards
2 functions of the testicles
- Testosterone production
- Leydig cells
- line seminiferous tubules
- production testosterone and androgens - spermatogenesis
- sertoli cells
- line seminiferous tubules
- production sperm
- mature in epididymis and stored in vas deferens
Testicular descent occurs when in utero
Descent from abdomen -> inguinal canal -> scrotum
last 3 months of development
Control of blood flow to Leydig Cells
Autonomic adrenergic neurons
Blood flow to surface of testicles
cools to 4 degrees
temperature for spermatogenesis
Function of the Epididymis
- Structural
- posterior testicle
- 5-7cm
- connection seminiferous tubules to vas deferens - Functional
- matruation sperm
- 12 days to swim across
- testosterone, nutrients
A. motility - maturation
- fertility
Function of the vas deferens
- storage of mature sperm
- muscular peristalsis for ejactulation
Anatomy and function of the prostate
- Seminal fluid
- high pH (alkaline)
- survival and motility of sperm
- secreted from the seminal vesicle
Size of walnut
- surrounds urethra
- common duct for sperm and urine
Brief summary Embryonic Male Development
Chromosome Y expression SRY signalling
TDF - testes determining factor
MIF - mullerian inhihitory factor (inhibition internal female genitalia)
Leydig cells secrete testosterone - testicle development (wolfian duct)
Male Hormones Gonad development
Definition
GnRH
- gonadotropin releasing hormone
- hypothalamus
- stimulates release of anterior pituitary gonadotrophins
LH
- leutinizing hormone
- Leydig cells
- production androgens and testosterone
- primary and secondary sexual characteristics (testicular development)
FSH
- follicle stimulating hormone
- Sertoli cells
- production sperm (spermatogenesis)
Testosterone
- produced by Leydig cells (testicles)
- produced by adrenal glands
- primary and secondary sexual characteristics
- anabolic (muscle, bone buildnig)
- libido
- hair, acne, sebaceous glands, etc.
List Structural Disorders
Penis
Cryptorchidism
- undescended testicle
Ectopic testicle
Phimosis
- unable to retract prepuce
Paraphimosis
- unable to reduce prepuce
Hypospadias
- uretra on the ventral side of the shaft
Peyronie’s disease
- fibrosis of penis results in bend
Cryptorchidism
Definition
Testicles do not descend to scrotum from abdomen
Unilateral > bilateral (high sterility)
Found anywhere along ectopic, abdomen, inguinal canal, suprapubic
palpable and non-palpable
Cryptorchidism
Incidence and Complications
3-4% at birth
1% remain undescended at 1 year
Complications
- infertility
- 50x increase risk of testicular cancer in adulthood (contralateral testicle)
Co-morbidities: anatomy
- vas deferens
- epididymis
- urethra, upper genital tract
- hypospadias
- mixed sex: both cryptorchidism + hypospadias
Cryptorchidism
Etiology
genetics x environment (hormones x structure x maternal age)
- Structural
- adhesions
- fibrosis
- narrowing inguinal canal
- no gubernaculum (cord that pulls them through) - Hormonal (environmental)
- insensitive to gonadotrophic hormones, maternal hormones - Maternal age
- advanced maternal age - Heredity (genetics)
When is physiological cryptorchidism normal
Retractile Testicle
- involuntary retraction of testes into inguinal canal (can be repositioned) in response to ANS activation
- cold, physical excitement
Cryptorchidism
Treatment
- Monitor for first month
- 50% descend in first month - Referral to urology MD
- 6 months
- Rx. Testicular ultrasound
- assess gonads and genitals (comorbidities) - Surgical intervention
- 6-18 months
Orchiopexy
- surgical descent of testicles
- 20% remain infertile
- retain 50x increase risk for testicular cancer
Phimosis
Definition
Inability to retract the prepuce (foreskin)
Two Types phimosis
- Congenital phimosis
- normal
- up to age 3 years should not retract the foreskin to clean - Poor hygiene
- not usually STI (can be)
- poor hygiene
- poor diabetic control (immunocompromised)
- secondary infection
Phimosis
Pathophysiology
Most commonly from poor hygiene
- inflammation
- swelling
- erythema
- edema
- pain
- discharge
–> cannot retract the foreskin
phimosis
Complications
- blanitis
- inflammation glans of penis - posthitis
- inflammation prepuce - paraphimosis
- inability to reduce the forskin
- cuts off circulation to glans of penis
- medical emergency
Phimosis
Treatment
- Treat infection and inflammation
- if infection, treat infection
- corticosteroid cream for inflammation
- control blood sugars if diabetic
- MD referral
- surgical release or circumcision
Phimosis
Incidence and risk factors
- can occur at any time, any age
- poor hygiene
- poor diabetic control
- not usually STIs
Paraphimosis
Definition
Inability to reduce the prepuce over the glans of the penis
Paraphimosis
Pathophysiology
Inflammation prepuce or glans
inability to reduce foreskin over
restriction blood flow to glans
MEDICAL EMERGENCY
Paraphimosis
Treatment
Surgical release or circumcision
Hypospadias
Definition
Urethral opening is on the ventral side of the penis (glans, shaft, base, penoscrotal junction, perineum)
Medical management
hypospadias
Referral to urology for surgical repair and assessment
Co-morbidities
- mixed, intersexed
- cryptorchidism
Peyronie’s Disease
Definition
“bent nail” disease
Inealstic fibrous scar/plaque in the tunica albuginea of the corpus cavernosa
Peyronie’s Disease
Risk factors
Age 40-65 years
collagen loss
Dupuytren contractures
beta blockers
diabetes
penile trauma
Peyronie’s Disease
Pathophysiology
Trauma to tunica albuginea / corpus cavernosa
Bleeding –> inflammation –> fibrosis
Peyronie’s Disease
Clinical Signs and Symptoms
- palpable fibrous lump
- bend when erect
- +/- pain on erection
- +/- erection / penetration
Peyronie’s Disease
Treatment
- Urology MD consult
- 50% will resolve in 12 monts - Pharmacological management
- L carnitine
- potassium aminobenzoate
- Q10
- Colchicine
- Collagenase clostridium histolyticum (CCH)
* more successful for early lesions - Surgical management
- suture
- Nesbit patch
List of Examples
Masses and Swelling of Testicles
- Testicular torsion
- Hydrocele
- Varicocele
- Spermatocele
Hypospadias
Etiology
Multifactoria
- genetic
- endocrine
- advanced maternal age
- low birth weight
Hypospadias
Complications
- Chordee (penile torsion)
- skin tethering
- penis bows/bends ventrally or to right/left side
Varicocele
Definition
Dilation of testicular veins, pampiniform plexus, resulting in backflow of blood into testicles
Varicocele
Pathophysiology and incidence
- Increase blood flow to testes
- adolescents (increased testosterone)
- 10% adolescents
- hot weather, exercise - Dysfunction of valves leads to backflow of blood into testes
- congenital defect - Tumor/thrombus leads to increase venous pressure
- Right sided varicocele
- older age - Dysfunction testes
- decreased spermatogenesis
- decreased androgen production
- atrophy of testicle (smaller size)
- low testosterone
- high FSH and LH
Varicocele
Clinical Signs and Symptoms
- symptomatic
- asymptomatic
Asymptomatic
- detected through infertility testing
- low sperm count
- low testosterone
- high FSH, high LH
Symptomatic
- Dull ache
- heaviness
- worse with exercise, warm weather, prolonged standing
- palpable spaghetti like cords
- small testicle on inspection
Varicocele
Right or Left Interventions
Left 90%
Right 10%
- BAD
- compression inferior vena cava
1. tumor
2. thrombus
- emergency referral
Varicocele Treatment Pathways
- Referral to Urology MD
- Mild (left side only) - watch
- Moderate/severe - varicocelectomy - Retroperitoneal US (moderate/severe, or right side)
- order to have prepared for referral
- R/O tumor, infarct - Doppler US of testes
- visualization venous distention of pampiniform plexus
Hydrocele
Definition
Most common cause of scrotal swelling
Fluid accumulation between tunica vaginalis (visceral and parietal) layers
Not usually associated with infertility
Hydrocele
Etiology
- Congenital hydrocele
- 6% infants
- majority resolves by 12 months - Vascular
- abnormal fluid secretion/asboprtion - Trauma
- trauma, torsion, surgery - Infection
- epididymitis
-orchitis
Hydrocele
Treatment pathways
- Non-communicating hydrocele
- watch and wait
- not usually associated with infertility
- majority congenital hydroceles resolve 12 months - communicating hydrocele
- urology MD referral
- aspriation
- sclerotherapy - Severity of symptoms
- asymptomatic/mild (watch and wait)
- moderate/severe (treatment) - Age
- < 2 years, watch and wait
Hydrocele
Clinical Signs and Symptoms
- painless swollen testicle
- unilateral or bilateral
- “swollen water balloon”
- worsens throughout day
- large swelling -> compression blood supply -> pain (communicating hydrogcele)
- infection = pain
Hydrocele
Diagnosis
- Transillumination
- Ultrasound
Spermatocele
Definition
Diverticulum of the epididymis
- fluid filled cyst located between epididymis and testicle
Spermatocele
Clinical Signs and Symptoms
- usually not painful
- asymptomatic
- palpable, freely movable mass (outside tunica vaginalis)
- cyst - filled with milky fluid, sperm
- not associated with infertility
- heaviness of testicle
Spermatocele
Treatment
- scrotal support
- removal if associated with pain
Painful vs. Non-painful
Testicular masses
non-painful
- testicular cancer
- hydrocele
- varicocele
- spermatocele
Painful
- epididymitis
- testicular torsion
- orchitis
Testicular Torsion
Definition
Torsion of the blood vessels (arteries, veins) supplying the testicles resulting in decrease blood flow and ischemia
Medical emergency
Needs to be treated within 4 hours
TWIST Score
Testicular Torsion
- Hard testicle / 2
- swelling /2
- N/V /1
- Cremasteric reflex absent /1
- riding high testicles / 1
Score
0-2 differential diagnosis
3-4 intermediate risk, referral, US
>5 emergency consult, immediate US
Clinical Signs and Symptoms
Testicular Torsion
- Hard testicles
- edema
- nausea and vomiting
- absent cremasteric reflex
- riding high testicle
- unilateral pain
- Prehn sign (not relieved by support of testicle)
Pathophysiology
Testicular Torsion
Etiology
- spontaneous (wake up in severe pain)
- trauma
- > incidence < 25 years of age
- any age
- Torsion of the vascular supply to testicles
- cut off blood flow
- ischemia, inflammation, necrosis
Testicular Torsion
Treatment
Surgical intervention within 6 hours 90% testicles saved;
12 hours 50% testicles saved
24 hours 10% testicles saved
Balanitis
Definition and pathophysiology
Inflammation of the glans (head) of the penis
*non-circumcized > circumcized
Accumulation:
- smegma (glandular secretions)
- epithelial cells
- mycobacterium (acid-fast bacterium)
- Candidiasis (yeast)
Balanitis
Etiology
- Non-infectious
- poor hygiene (pre-pubescence)
- trauma
- skin condition (psoriasis, eczema, lichen plantus)
- drug reaction - Infectious
- Mycobacterium
- STD
- Candidias
*R/O with culture and sensitivity swab
Balanitis
Complications
Posthitis
- inflammation of the prepuce
Paraphimosis
- inability to reduce the prepuce
Phimosis
- inability to retract foreskin
Blanoposthitis
- inflammaiton both prepuce and gland of penis
Blanoposthitis
Definition
Co-occurance of posthitis (inflammation prepuce) + balanitis (inflammation glans of penis)
*usually occur together
Risk factors
Balanitis
- Immunocompromised
- Poorly controlled diabetes
- non-circumcized
- pre-pubescent males
- poor hygiene
Treatment
Balanitis
- Hygiene Education
- Clean daily, lukewarm water
- avoid soaps, lubricants, baby wipes
- retract foreskin > 3 years of age vs. clean under foreskin
- Treat inflammation and/or infection
- Inflammation:
Hydrocortisone 1% maximum 14 days - Yeast infection:
Azole cream + hydrocortisone 1% for maximum 14 days - Mycobacterial infection:
PO cloxacillin/cephalexin/clarithromycin 7 days, hydrocortisone cream 1% for 14 days
- Referrals
- Urology/dermatology
- circumcision for refractory cases
-*investigate immunocompromised conditions (diabetes, HIV, etc.)
Urethritis
Definition
Inflammation of the urethra
*Most commonly STD
Urethritis
Etiology
- Infectious
- Non infectious
Most common STDs
Clinical signs and symptoms after 1 week:
Neisseria gonorrhea
- gram negative cocci
- symptoms develop in 1 week after contraction
Clinical signs and symptoms 1-5 weeks after:
Chlamydia trachomatis (gram negative)
mycoplasma genitalium (gram negative)
ureaplasma urealyticum (gram negative)
Trichomonas (protozoan)
candidia albicans (yeast)
herpes simplex virus
adenovirus
Clinical Signs and Symptom
Urethritis
- Asymptomatic (males > females)
- dysuria
- burning
- pruritis
- erythema
- +/- discharge (mucopurulent/mucoid/purulent/bleeding)
- obstruciton/urgency/retention
Urethritis
Empirical Treatment
Empirical treatment treats for BOTH N. gonorrhea and C. trachomatis (co-occurring infections)
Ceftriaxone 250mg IM once
+
Azithromycin 1g PO once OR doxycycline 100mg BID for 7 days
*Non-gonococcal (asymptomatic, culture and sensitivity swab)
Azithromycin 1g PO once
OR
Doxycycline 100mg BID for 7 days
Patient Education
Urethritis
- All partners in last 60 days to be treated
- Reported to public health
- Test for cure for 1-2 weeks after infection (*if alternative regime used)
- Symptom resolution 7-14 days post antibiotics
Urethritis Treatment
Special populations
- Pregnancy & Children
Ceftriaxone
Azithromycin
*Doxycycline is contraindicated in pregnancy and children
- Allergy to penicillin
Ciprofloxacin + Azithromycin OR
Azithromycin + gentamicin
*Test for cure > 1-2 weeks after therapy (3-4 weeks if NAAT being used)
Non-infectious causes Urethritis
- inflammation
- trauma
- urological procedure
- foreign bodies
- autoimmune reactive arthritis (Reiter syndrome - shigella, campylobacter, chlamydia)
Epididymitis
Definition
Inflammation of the epididymis
Epididymitis
Etiology
Most commonly sexually active males < 35 years (rare before puberty)
- Sexually transmitted infection (Individuals < 35 years)
- Non-sexually transmitted infections (Individuals > 35 years)
- Sterile
STI Causes:
- Neisseria gonorrhea
- Chlamydia trachomatis
- Enterobactericeae (unprotected anal sex)
Non-sexually transmitted infection
- Cloriform
- Pseudomonas aeruginosa
- E. coli
- *hematogenous spread from genitourinary tract or chronic prostatitis
Sterile
- urine - structural reflux urine into epididymis
- drug - amiodarone therapy
- vasculitis (Behcet disease, henoch-schonlein purpura, polyarteritis nodosa)
- idiopathic
- urology procedure
Chemical epididymitis
- reflux of urine into the epididymis
- Heavy lifting
- sterile form of epididymitis
Clinical Signs and Symptoms
Epididymitis
- Acute unilateral testicular pain
- Palpable swelling and pain (spermatic cord, testicles, epididymus (lower pole -> head))
- testicular erythema and swelling
- hydrocele (fluid between tunica vaginalis)
- Fever, malaise, fatigue (infection)
- +/- discharge (discharge = STI)
- Relief of pain with testicular support (Prehn Sign)
- UTI symptoms - urethritis
- prostitis symptoms
*infection ascends the urether
Complication
Epididymitis
- abscess
- infarcts (testicles, prostate)
- chronic epididymis and scaring (antibiotics cannot reach the site of infection)
- infertility
Co-morbidities
Epididymitis
If the epididymitis is infectious:
- Prostitis
- urethritis
- urinary tract infections
*infectious organism ascends the urethra –> prostate –> vas deferens / bladder
Differential diagnosis
Epididymitis
- Testicular torsion
- sudden pain
- TWIST score: N/V, hard testicle, swelling testicle, riding high testicle, no cremasteric reflex, no prehn sign, unilateral - Testicular cancer
- progresses over weeks, not acute
- low grade pain
Treatment
Epididymitis
- Etiology: STI (N. gonorrhea / C. trachomatis)
- Ceftriaxone 250mg IM once AND
- Azithromycin 1g PO once
- doxycycline 100mg BID for 10-14 days
- Etiology: non-STI or enteric organisms
- Ciprofloxacin 500mg BID for 10-14 days
- Levofloxacin 500mg once daily for 10-14 days
Special populations
Epididymitis
Penicillin Allergy
Ciprofloxacin/Levofloxacin 500mg ONCE
Azithromycin 1g PO ONCE
Doxycycline 100mg BID for 10-14 days
Causative organism
Epididymitis incidence
< 35 years of age OR multiple sexual partners OR purulent discharge
STI
N. gonorrhea / C. trachomatis
Empirical treatment
ceftriaxone 250mg IM once
azithromycin 1g PO once
doxycycline 100mg BID 10-14 days
> 35 years of age
Assume non-STI and gram negative enterococci
Empirical treatment
ciprofloxacin 500mg BID /levofloxacin 500mg OD for 10-14 days
*Re-assess if symptoms persist after 3 days
Patient Education
Epididymitis
- return to doctor if symptoms do not resolve in 3 days (re-assess empiric treatment)
- public health reportable
- all partners treated within 60 days
Duration of therapy
Epididymitis
Minimum 10-14 days
*secondary to chronic prostatitis
up to 6 weeks of antibiotic therapy
Prostatitis
Definition and types
Inflammation of the prostate
- Acute prostatitis
- Chronic prostatitis
- Bacterial prostatitis
- non-bacterial prostatitis
- Idiopathic
Acute Prostatitis
Clinical Signs and Symptoms
*Similar to UTI
- Fever, chills, malaise
- perineal, rectal, lower back pain
- irritative/obstructive voiding
- Pain worse when standing (pelvic floor contracts prostate)
- palpation prostate enlarged, swollen, tender, indurated, warm
Diagnostic and laboratory tests
Prostatitis
obtain urine sample before empiric treatment
Acute Prostatitis
Treatment
MUM’s Guideline
10-14 days
re-assess
- Ciprofloxacin 500mg BID for 3-4 weeks
- Levofloxacin 500mg OD for 3-4 weeks
- Norfloxacin 400mg BID for 3-4 weeks
- TMP/SMX
Additional 2-4 weeks needed after symptoms have resolved to prevent chronic prostatitis
Acute Prostatitis
Unable to void
Treatment
Hospitalization
- IV antibiotics
- Suprapubic catheterization (foley contraindicated)
Ampicillin IV OR Ceftriaxone IV
+
Gentamicin IV OR tobramycin IV
Chronic Prostatitis
Clinical Signs and Symptoms
*Relapsing UTI suspect chronic prostatitis
- urinary frequency, urgency
- urinary retention
- dysuria
- ejactulatory pain
- pelvic or genital pain
- hemospermia
- some patients are asymptomatic
- prostate exam is usually normal
Chronic Prostatitis
Incidence
Incidence increases with age
Chronic Prostatitis
Diagnostics and treatment
- Urine culture and sensitivity
Syndrome approach (cultures may be negative)
- Antibiotic treatment
- Levofloxacin 500mg once for 4-6 weeks
- Ciprofloxacin 500mg BID for 4-6 weeks
SECOND LINE
- TMP/SMX - Alpha blockers
- TeraZOSIN
- block alpha receptors, relaxation smooth muscles - Referral to urology MD
- no resolution 4-6 weeks
Non-pharmacological treatment
Prostatitis
- Anti-inflammatories
- hot sitz bath
- bedrest (relaxation pelvic floor muscles)
Complication
Prostatitis
- Prostatic caliculi
- stones in the prostate
- infected with bacteria
- hard to eradicate
- Rx. surgical removal - Inflammatory chronic pelvic pain syndrome
- chronic pain
- perineal, testicular, penile, lower abdomen, ejactulatory
- dysuria, hesitancy, interrupted flow
- exacerbated by sexual activity - Chronic prostatitis
- Abscesses
- Bacteremia
- Epididymitis
Orchitis
Definition
Inflammation of the testicles and scrotal sac secondary to epididymis infection or secondary to systemic illness (Ex. Mumps, COVID19)
Orchitis
Clinical Signs and Symptoms
- Secondary to infection: Fever, WBC
- Inflammation: swelling, erythema to testicles, pain
- unilateral or bilateral
- +/- hydrocele
- prostration (doubled over in pain)
Orchitis
Pharmacological and Non-pharmacological Treatment
Pharmacological
- Treat infection
- COVID19 antivirals
- Bacterial epididymitis
- No pharmacological treatment for mumps
Non-pharmacological
- bed rest
- support testicles
- ice
- anti-inflammatories
Complications
Orchitis
Infertility
menarch
menstruation
occurs 2.5 years after thelarche in females
Thelarch
emergence of breast buds
approximately 8 years-12 years females
= gonadarche for females
stage 2 tanner
pubarche
pubic hair appearance
8 years of age
stage 2 tanner
gonadarche
formation testes males and ovaries females
stage 2 tanner development
corresponding to thelarche in females
Stage 2 tanner
Pre-puberty
hypothalamus-pituitary axis
GnRH
gonadotropin releasing hormone
LH
leutinizing hormone
FSH
follicle stimulating hormone
low levels of all hormones
FSH > LH
Puberty
Hypothalamus- pituitary axis
surges of FSH and LH at night time during REM sleep
small release GnRH results in large release FSH and LH
LH > FSH
Male Secondary sexual characteristics are controlled by what hormone?
LH
leutinizing hormone
results in release of testosterone from leydig cells
secondary sexual characteristics - hair, growth, muscles, testicles
FSH
follicle stimulating hormone
results in spermatogenesis from sertoli cells in the seminiferous tubules in the testicles
Female secondary sexual characteristics, controlled by what hormones
LH
leutinizing hormone
results in release of estrogen from the theca cells in the ovaries
Estrogen receptors in ovaries, placenta, breast tissue
FSH
follicle stimulating hormone
promotes development of the ovarian follicle and stimulates estrogen secretion
FSH and LH spike occurs on day 14 of the cycle
Female hormones during ovulation
LH and FSH spike
promote ovulation
Estrogen and LH highest during ovulation
progesterone is highest post-ovulation
Effect of estrogen
Non-reproductive
- bone density
- liver: decrease LDL, increase HDL
- CNS: memory, cognition
- Skin: collagen, elasticity, healing
- Kidney: protective against CKD
- CVS: prevents atheroscelerosis, platelet adhesion
Effects of estrogen
Reproductive
Vaginal mucosa: growth squamous epithelium
cervical mucosa: fluid secretions, motility sperm increased and survival increased
fallopian tubes: motility and cillia action inrease
Uterine muscles: increase blood flow, contraction, oxytocin sensors
Endometrium: growth, increase progesterone receptors
breasts: ducts, prolactin increase
Effects of progesterone
Reproductive
vaginal mucosa: thinning squamous epithelium
Cervical mucosa: thickening, plug cervix
Fallopian tube: decrease ciliary motility
Uterine muscles: relaxation, decrease sensation oxytocin
endometirum: decrease estrogen receptors, activate glands, blood vessels
breasts: growth lobules, alveoli, inhibition prolactin
