Final Exam Flashcards
What maintains testicle temperature of 34°C?
• pampiniform plexus
• spermatic cord cremaster muscle
• scrotum dartos muscle
What is the abdominal peritoneal process that covers the tunica albuginea?
Tunica vaginalis: sac that surrounds anterior and lateral parts of the testes.
What is the tunica albuginea?
Blue gray fibrous membrane that covers the testis. Septa divides lobules and mediastinum of testes
What are the components inside of the tunica albuginea?
1. Seminiferous tubules
• Sertoli cells (endocrine, inhibin)
• germ cells (exocrine, sperm)
2. Interstitial connective tissue
• peritubular myoid cells (contractile smooth muscle)
• interstitial cells of Leydig (endocrine factors- steroids, testosterone)
What is the spermatogenic wave?
• spermatogenic cells replicate and differentiate into mature sperm in waves throughout different portions of the seminiferous tubules
What is spermatogenesis?
The formation of spermatozoa from spermatogonia
What is spermiogenesis?
The last stage of spermatogenesis which includes the maturation of the spermatozoa and acquisition of motility
What are the three classes of spermatogonia?
- Dark type A (reserve stem cells)
- Pale type A (renewing stem cells)
- Type B (differentiating progenitors)
What are the four phases of spermiogenesis?
- Golgi: Golgi become acrosome, axoneme formed, centriole forms manchette
- Cap: acrosomal vesicle forms (Will breakdown Zona pellucida of ovum)
- Acrosomal: head of sperm forms and orients towards base of seminiferous tubule
- Maturation: residual bodies shed, spermiation (release of sperm ) occurs
Spermatozoa anatomy
What are Sertoli cells?
• true epithelial cells of the seminiferous tubules
• they formed the blood testes barrier with tight junctions
What type of receptors are on Sertoli cells?
FSH receptors: they produce androgen binding protein (ABP) and inhibin
What are the interstitial cells of Leydig?
• compact groups of cells with large, eosinophilic cytoplasm and round nuclei. Extensive smooth ER
• may have crystalloid inclusions (Reinke crystals)
• steroid/ testosterone production
Estrogen promotes what in the testes?
Spermatogenesis and sperm maturation (Sertoli, leydig, and germ cells all express aromatase to convert testosterone to estrogen)
Are leydig cells temperature sensitive?
No, therefore cryptorchidism has no effect on androgen output (only affects sperm production)
What is the rete testis?
• labyrinth plexus of epithelially-lined channels in the mediastinum of the testes (simple cuboidal cells)
What types of cells line the efferent ductules of the testes?
Simple columnar epithelium— alternation of tall cells (ciliated) and short cells (microvilli)
What are the cells composing the epididymis?
• pseudostratified columnar epithelium:
- Principal cells containing stereocilia
- Basal cells that act as stem cells
What is the Vas deferens?
• Long, very thick muscular wall that runs through the spermatic cord containing arteries, veins (pampiniform), lymph vessels, nerves, skeletal muscle (cremaster)
• composed of pseudo stratified columnar epithelium with stereocilia
• three muscular layers: inner longitudinal, middle circular, outer longitudinal
What are the seminal vesicles?
• unbranched tubular diverticulum of the distal end of the vas deferens
• composed of mucosa creating cavities, epithelium (columnar) containing clumps of yellow lipochrome pigment
• dependent on testosterone levels
What is the purpose of the Seminal vesicles?
• secretion of fluid high in fructose, ascorbic acid, prostaglandins, and fibrinogen that contributes 80% of the total volume of ejaculate
The prostate gland is dependent on what for development?
Dihydrotestosterone (DHT)
What are the four zones of the prostate gland?
- Central
- Peripheral
- Transitional
- Periurethral
What are the cells of the prostate?
• highly folded epithelium made of simple cuboidal to simple columnar
• cells contain secretory vesicles and yellowish lipoidal droplets (conceptions)
What is the function of the prostate?
• secretion of a thin, milky, faintly acid fluid for ejaculation
• contains PAP (acid phosphatase), PSA, and proteolytic enzymes
• activity is testosterone dependent
What are the bulbourethral/Cowper’s glands?
• paired bodies that lie in the connective tissue behind the membranes urethra
• sexual arousal causes pre-ejaculation from the glands for lubrication (comparable to Bartholin’s glands)
Anatomy of the penis
Penile erection is caused by what?
• parasympathetic stimulation: smooth muscles dilate, blood flows rapidly into cavernous spaces, venous drainage is reduced, maintains erection
Ejaculation occurs by what nerve?
S2-4 pudendal nerve
What causes detumescence?
Erection termination caused by sympathetic stimulation—> arteries regain tone and venous blood flow can occur
What are the three portions of the male urethra?
- Prostatic
- Membranous
- Penile
What is the purpose of androgen binding protein?
It keeps intracellular and gonadal testosterone high
What are the effects of androgens?
Male characteristics: hair growth, spermatogenesis, libido
What are the anabolic effects of androgens?
Promote cell growth: bone growth, RBC growth, muscle growth
A high androgen to anabolic ratio is a good medication for what?
• hormone replacement therapy
• hypogonadism
• trans men
A high anabolic to androgen ratio as a medication is good for what?
• anemia (RBC increase)
• osteoporosis
What types of medications are used to support fertility in men?
• androgens with a high androgen: anabolic ratio
• pulsatile infusion of GNRH agonist to promote FSH/LH
• FSH/LH injections to promote testosterone and spermatogenesis production
What drugs are used for chemical castration?
• androgen antagonist to block testosterone action
• GnRH agonist, continuous non-pulsatile also suppresses testosterone
What is used as a medication to promote hair follicle growth?
5-Alpha reductase inhibitors to suppress ditestosterone production
What medications are used for prostatic hyperplasia?
• 5-Alpha reductase inhibitors
What is a drug used for erectile dysfunction?
Phosphodiesterase-5 inhibitors (PDE5 inhibitors) to inhibit cGMP
What is Dagarelix?
GnRH antagonist
What are leuprolide, gonadorelin, and goserelin?
GnRH agonists: activating when pulsatile, inhibiting when continuous
What are finasteride, dutasteride?
5-Alpha reductase inhibitors
What are the PDE5 inhibitors?
Sildenafil, tadalafil, and vardenafil
What drugs are androgen antagonists?
• bicalutamide
• flutamide
• nitulamide
• apalutamide
• enzalutamide
What drugs are general steroidogenic inhibitors?
• ketoconazole
• aminoglutethimide
• spironolactone
What is abiraterone?
Androgen synthesis (CYP177A1) inhibitor
What is the difference between a continuous GnRH agonist and a GnRH antagonist?
The GnRH continuous agonist causes an initial LH/FSH hypersecretory phase
What cannot be used as pro fertility drugs in males?
Exogenous androgens: they cannot replace testicular androgens, difficult to attain high-level, end up inhibiting GnRH and gonadotropins
pulsatile GRH analogues are the best option for promotion of fertility
What is a side effect of anabolic androgenic steroids?
They shut down the HPG leading to hypopituitary function due to negative feedback of androgenic receptor stimulation in hypothalamic GnRH neurons and gonadotrophs of the pituitary
What medications are used to reduce excessive sexual drive in men?
Anti-androgens (antagonists): cyproterone acetate and medroxyprogesterone acetate
What drug can be used as acne/facial hair reduction?
Anti-androgen (anti-ADH): spironolactone
Why are PDE5 inhibitors used in the treatment of erectile dysfunction?
They elevate NO release from parasympathetic cavernous nerves that stimulate guanylyl cyclase to produce cGMP which leads to reduction in free intracellular calcium and relaxation of smooth muscles
What is prostatitis?
Infection/inflammation of the prostate:
• acute (neutrophils in the prostate and acute inflammation in the lumens)
• chronic (lymphocytes in the stroma)
What is seen in prostate granulomatous inflammation?
• necrosis
• histiocytes
• multinucleated giant cells
• lymphocytes
What is benign prosthetic hyperplasia (BPH)?
• nodular hyperplasia of the stroma and epithelium of the prostate transitional zone causing obstruction of the prosthetic urethra
• DHT is the primary driver of hyperplasia
• symptoms: difficulty voiding, urinary retention/frequency/nocturia, hypertrophy of the bladder muscularis
What is the cause of hyperplasia in BPH?
Impaired cell death (rather than proliferation) that is mediated by androgens
What is prostate carcinoma?
• most common cancer in men
• most commonly acinar type in the peripheral zone (does not cause urinary symptoms)
• bone is a common site of metastasis
What are the molecular findings of prostate carcinoma?
• androgen receptor +
• fusion TMPRSS2: ETS gene
• other mutations: BRCA2, PTEN, TP53, RB
What is the histologic criteria of prostate cancer?
• small, crowded glands
• nuclear enlargement with luminal mucin, crystalloids
• absent basal cell layer, therefore HMK and p63 staining negative
• AMACR stain positive
What are the Gleason stages of prostate carcinoma?
grading based off of microscopic morphology alone
1/2: discrete regular glands, circumscribed, round nodules
3: market variation in size/shape of glands, infiltration between non-neoplastic acini
4: fused microacinar glands, poorly formed, crib performing, glomeruloid
5: Minimal glands, solid sheets/cords/cylinders, solid cribiform or papillary structures with central necrosis
What is the Gleason score based off of?
The primary and secondary patterns of tumor added together
Path of sperm exiting the body:
SEVEN UP
S- seminiferous tubule
E- epididymis
V- vas deferens
E- ejaculatory duct
U- urethra
P- penis
Seminal secretions come from where?
- Seminal vesicles
- Prostate
- Bulbourethral gland
What is contained in semen?
Sperm, bicarbonate, energy substrates (fructose, citric acid), prostaglandins/motility factors, clotting proteins, proteolytic proteins (including PSA)
What is secreted by Sertoli cells?
Androgen binding protein (ABP), inhibitin, activin
Graph/image depicting testosterone negative feedback
The relationship between FSH and testosterone in the ability to produce sperm is what?
Synergistic
Balanoposthitis
• inflammation of the penis due to an infection of the glans and prepuce
• typically from a candida infection, poor hygiene and uncircumcised are main risk factors
Balanoposthitis
• inflammation of the penis due to an infection of the glans and prepuce
• typically from a candida infection, poor hygiene and uncircumcised are main risk factors
What are phimosis and paraphimosis?
• phimosis: the orifice of the prepuce is too small to permit retraction, may be congenital or repeated bouts of balanoposthitis
• paraphimosis: a retracted Pre with a small orifice cannot be reduced back over the glans— surgical emergency
What is the most common cause of squamous cell neoplasia of the penis?
• non-HPV related/differentiated: association with inflammatory conditions, on the foreskin, apparent and rapid progression to invasion
What are the HPV related/undifferentiated in situ to lesions leading to squamous cell neoplasia of the penis?
- Bowen disease: leukoplakia
- Erythroplasia of queyrat: erythroplakia
- Bowenoid papulosis: rare/never progression
What can cryptorchidism lead to histologically?
- germ cell arrest: may only see sertoli cells
- basement membrane thickening
- tubular atrophy making leydig cells appear prominent
What is a hydrocele?
• persistent communication between the peritoneal cavity and the potential space of the tunica vaginalis and the testicle— fluid accumulation
• transilluminates
What is a hematocele?
• trauma leading to bleeding that expands into the same space as a hydrocele
• does not transilluminate, must be drained due to clotting risk— orchiectomy
What is spermatocele?
• dilation of a portion of the epididymis or rete testis
• Leading to a cyst that contains sperm seen in the head of the epidermis
• aspirate or excise if symptomatic
What are the germ cell tumors that arise from GCNIS?
• seminoma
• embryonal carcinoma
• yolk sac tumor
• choriocarcinoma
• teratoma, post puberty
What are germ cell tumors that do not arise from GCNIS?
• teratoma, pre-puberty
• yolk sack tumor, pre-puberty
• spermatocytic tumor
What are the sex cord of stromal tumors?
- Leydig cell tumor
- Sertoli cell tumor
Germ cell neoplasia in situ has increased expression of what transcription factor?
OCT 3/4: maintains pluripotency and renewal of stem cells
A seminoma typically metastasizes to what lymph nodes?
Iliac, paraaortic
What is the appearance of an embryonal carcinoma of the testicle?
• early metastasis to lymph nodes and hematogenous spread- tumor everywhere
• hemorrhagic, pleomorphic, poorly differentiated malignancy
What are the unique features of a choriocarcinoma of the testicle?
• very aggressive, hemorrhagic mass made of cytotrophoblasts and synciotrophoblasts ( INCREASED bhCG!!)
• common hematogenous spread and symptoms (hemoptysis, stroke, etc.)
What are the common features of a yolk sac tumor of the testicle?
• Schiller Duvall bodies (glomeruloid-like)
• elevated AFP!!
What is the difference between a pre-pubertal and post-pubertal teratoma of the testicle?
Prepubertal: not associated with GCNIS, pure teratoma, excellent prognosis
Postpubertal: associated with GCNIS, rarely pure/part of mixed germ cell tumor, malignant
What is the most common testicular tumor in men over 60?
Lymphoma: DLBCL
What are the diagnostic test to determine testicular torsion?
- Cremaster reflex (stroke opposite inner thigh)
- Prehn sign (elevation of the affected testicle does not relieve symptoms— it would in epididymitis)
- Color Doppler to determine blood flow
- Observation (affected testicle may be horizontal instead of vertical)
Thayer-Martin media is used for isolating what bacteria?
Neisseria species
Chlamydia trachomatis: serovars
serovars A-C: transmitted through hand to iContact which allows for infection of the conjunctiva. Inflammation promotes corneal vascularization and scarring leading to corneal damage and eventually blindness
serovars D-K: infection of the columnar epithelium of the GU tract leading to PID. May lead to infection of the liver capsule (Fitz-Hugh-Curtis syndrome)
serovars L1-L3: sexually transmitted and painless ulcer, lymphogranuloma venereum, can lead to proctitis and renal strictures
What is the infection pattern of chlamydia trachomatis?
• extracellular: elementary body is infectious
• converts to reticulate body, non-infectious
• reticulate bodies grow and emerge overtime to form an inclusion body
• inclusion body spills elementary bodies out of the cell to infect other cells
What does a Tzanck smear look for?
Herpes simplex virus: positive for giant multinucleated cells
Acyclovir treatment image/graph:
How do herpes viruses gain resistance to acyclovir?
- Mutations to the thymine kinase
- Mutations to the DNA polymerase
When are clue cells visible on wet prep?
Bacterial vaginosis: Gardnerella vaginalis (white/gray discharge, very malodorous, KOH whiff test)
What organism is a protozoa responsible for a vaginal infection with itchiness, and yellow discharge?
Trichomonas vaginalis
~ tx: metronidazole
Name the vaginal infection:
Candida albicans— nearly always opportunistic, diabetic and pregnant woman may be predisposed
How do we test for syphilis (treponema pallidum- spirochete)?
Rapid plasma regain (RPR) serologic test, PCR, dark-field microscopy, antibodies to Cardiolipin
What is the treatment for syphilis?
Penicillin G at all stages (primary, secondary, and tertiary)
70 to 80% of prostate cancer occurs where?
In the peripheral zone
What genetic mutations lead to an increased risk for prostate cancer?
• BRCA 2
• HNPCC
~ screen at 40 years, monitor frequently if patient has these mutations
Are testosterone and DHT levels associated with increased prostate cancer?
NO
Dioxin (agent orange used in Vietnam war) is associated with what type of cancer?
Prostate
What are the ways of detecting prostate cancer?
- PSA
- Digital rectal exam
- Transrectal ultrasound
- Biopsy
When monitoring PSA, what must be evaluated?
• percent free PSA (not bound to protein)
• PSA velocity
• PSA density (level in comparison to prostate size)
What is another measure of prostate cancer other than PSA?
Prostate acid phosphatase (enzyme produced by the prostate)
What is the common age for discussion of PSA and prostate screening in men?
55 to 69 years old
What is the best option for low-grade prostate cancer treatment?
Active surveillance
What are enzalutamide and darolutamide?
Androgen receptor blockers used in prostate cancer, oral
What is abiraterone?
A pregnenalone analog that competitively inhibits CYP17 (17alpha- hydroxylase). This blocks testosterone production in the testes, prostate and blocks DHEA production in the adrenal zona reticularis
Oral.
What is degarelix?
GnRH antagonist used for the treatment of prostate cancer.
Subcutaneous
What is leuprolide?
GnRH super agonist (continuous admission leads to inhibition). A short tumor flare (increase in FSH/LH before inhibition)
Subcutaneous or intramuscular
What is docetaxel?
A taxane drug typically combined with prednisone to treat prostate cancer. Inhibits tubulin (microtubule) depolymerization leading to mitotic catastrophe
IV only.
What is olaparib?
A PARP inhibitor used for the treatment of breast cancer with known BRCA1/2 mutations. Prevents initiation of damaged DNA repair
Oral.
What is tamoxifen/fulvestrant?
Selective estrogen receptor inhibitor. Tamoxifen works as an antagonist in the breast but agonist in other tissues. Fulvestrant is a pure anti-estrogen in all tissues.
Tamoxifen: oral
Fulvestrant: intramuscular
What are letrozole/anastrozole?
Competitive aromatase inhibitors used in breast cancer. They block the production of estrogen in the granulosa cells.
Oral.
What is palbociclib?
A CK4/6 inhibitor used in the treatment of breast cancer. (Kinase activity of cyclin D and CK4/6 is often elevated in breast cancer— amplification of the CCND1 gene)
What is trastuzamab?
Small molecule tyrosine kinase, HER2 / ERBB2 inhibitor used in HER2+ breast cancer
