Endo Flashcards
Describe the male reproductive system anatomy
EXAM and own notes
Scrotum
* Loose skin and superficial fascia sac that hangs from root of penis
* Dartos muscle: smooth muscle (involuntary) that contracts when cold and relaxes when hot
* Cremaster muscle: skeletal muscle (voluntary) continuation from internal oblique muscle -
elevates testes when cold (one on each side)
Testes
* Paired, oval glands suspended by spermatic cords in scrotum
* Development: near kidney, then descend through inguinal canal
* Seminiferous tubules: long, coiled tubes that produce spermatozoa
* Tunica albuginea: fibrous capsule that extends corpora cavernosa and spongiosum
* Tunica vaginalis: made of peritoneum (descends through inguinal canal during embryology)
* Outer parietal layer and inner visceral layer with cavity of tunica vaginalis between them
* Clinical
* Cryptorchidism: undescended testes
* Hydrocele: accumulation of fluid in cavity of tunica vaginalis causing swollen scrotum
* Sometimes, residual part of peritoneum doesn’t close off completely during
development so peritoneal fluid trickles down and accumulates
* Communicating: large defect that allows communication with peritoneal cavity
* Non-communicating: smaller defect
* Inguinal hernia: defect is big enough that small intestine can loop through
* Direct: passes through upper part of abdominal wall
* Indirect: passes through inguinal canal
* Varicocele: vessels on both sides become enlarged - associated with decreased fertility
* Testicular torsion: twisted spermatic cord causes testicular arteries and veins to be twisted
(testicle loses supply)
* Sudden and severe scrotal pain is testicular torsion until proven otherwise → can
necrotise within 6 hours
Spermatic cord
* Location: passes through inguinal canal
* Contains: vas deferens, testicular artery and pampiniform veins, lymphatic vessels and
autonomic nerves
* Pampiniform plexus: coil of veins that take blood back from testes to systemic circulation
(heat exchange) → drain into left renal vein
* Testicular artery arises from abdominal aorta
Ducts
* Epididymis:
* Comma-shaped with head, body and tail - attaches to posterior
aspect of testis
* Structure: coiled ductus epididymis (6 metres) - continuous with vas
deferens
* Function: sperm maturation and storage
* Vas (ductus) deferens (spermatic cord): wall of smooth muscle
* Continuation of epididymis - 45cm long within spermatic cord
* Course: inguinal canal (internal and external rings) → crosses ureter
→ behind base of bladder → joins seminal duct to form ejaculatory
duct
* Function:
* Transport system from epididymis to ejaculatory duct
* Storage of spermatozoa in ampulla of vas deferens
* Clinical:
* Vasectomy: permanent birth control cutting vas deferens
* Congenital absence of vas deferens in CF
* Ejaculatory duct
* Union of vas deferens and seminal vesicle duct above prostate gland
→ passes through prostate and terminates in prostatic urethra
Inguinal canal and rings
* Inguinal canal: slit-like passage above and parallel to inguinal ligament -
extends from deep inguinal ring to superficial inguinal ring
* Contains inguinal nerve and spermatic cord (males) or round ligament
of uterus (females)
* Deep (internal) inguinal ring: between anterior superior iliac spine
and pubic symphysis due to invagination of transversalis fascia
* Superficial (external) inguinal ring: superficial to pubic tubercle,
opening in aponeurosis of external oblique
Accessory glands
* Seminal vesicles:
* 2 coiled sacculated tubes
* Location: base of bladder, lateral to vas deferens
* Function: secrete 60% of fluid of semen - alkaline, fructose (coagulation)
* Prostate:
* Inverted chestnut shape perforated by prostatic urethra and ejaculatory duct → fibromuscular and
glandular tissues
* Location: inferior to bladder neck and above external urethral sphincter, anterior to rectum
* 3 ducts: prostatic urethra and L/R ejaculatory ducts
* Lobes: left, right, anterior, posterior and median
* Function
* Secretes alkaline milky fluid (25% of semen) - liquifies semen
* Provides energy for sperm
* Clinical
* Benign prostatic hypertrophy (>45 year): median lobe can encroach on prostatic urethra and
cause inability to urinate
* Prostate cancer
* Bulbourethral (Cowper’s) glands
* Location: inferior to prostate, lateral to urethra above penis bulb (within urethral sphincter)
* Function: lubricate urethra
Penis
* Glans penis: distal, enlarged acorn-shaped containing external urethral orifice and foreskin (prepuce)
* Body of penis
* Corpus spongiosum: single, mid-ventral (underside) tissue containing spongy urethra for semen and
urine to pass
* Corpus cavernous: paired dorsolateral (top) main erectile tissue that fills with blood - covered by tunica
albuginea
* Root of penis
* Crus: paired structures formed by tapered corpora cavernosa
* Surrounded be ischiocavernosus muscle (involved in erection)
* Bulb: enlarged corpus spongiosum
* Surrounded by bulbospongiosus muscle → provides propulsive force for ejaculation
* Clinical:
* Phimosis: tight foreskin
* Paraphimosis: foreskin gets stuck behind corona and cannot be retracted - severe oedema
Route of sperm
1. Spermatozoa produced in testes in semniferous tubules
2. Rete testis (network of tubules)
3. Epididymis (storage as they mature) head → body → tail
4. Vas deferens (travels through inguinal canal behind bladder)
5. Spermatic cord
6. (+ seminal vesicle duct) Ejaculatory duct → prostate
7. Prostatic urethra
8. Membranous urethra
9. Bulbar urethra
10. Spongy penile urethra
Lymphatic drainage of testes and scrotum
* In testes, lymph drainage follows blood vessels directly to para-aortic lymph
nodes (same as other retroperitoneal organs)
* Scrotum lymph drains to local superficial inguinal nodes then travels up
further before finally draining into para-aortic nodes
* Testicular cancer: inguinal orchidectomy or scrotal orchiectomy
* Cutting the skin in the scrotum may disrupt the natural drainage
patterns of the testes, so cancer may spread to the inguinal lymph
nodes, making surveillance and subsequent operations more difficult
HI
Describe the route of sperm
Y2, EXAM, own notes
Route of sperm
1. Spermatozoa produced in testes in semniferous tubules
2. Rete testis (network of tubules)
3. Epididymis (storage as they mature) head → body → tail
4. Vas deferens (travels through inguinal canal behind bladder)
5. Spermatic cord
6. (+ seminal vesicle duct) Ejaculatory duct → prostate
7. Prostatic urethra
8. Membranous urethra
9. Bulbar urethra
10. Spongy penile urethra
Describe the female reproductive system
EXAM and own notes
Female external genitalia
* Mons pubis: fat over pubic symphysis
* Labia majora: bulky folds of skin
* Labia minora: small folds of skin between major over
vestibule
* Clitoris: erectile structure with 2 crura, a body and a glans
* Vestibule: area between labia minora
* Several openings
* External urethra
* Vagina
* Ducts of greater vestibular glands (Bartholin’s):
posterior to bulb - responsible for vaginal lubrication
* Can form cyst if blocked
* Hymen: membrane over vaginal orifice
* Muscles
* Bulbospongiosus within labia minora
* Ischiocavernosus (parallel to ischiopubic rams)
Perineum
* Perineum: diamond-shaped area between thighs and buttocks from pubis
to coccyx that contains external genitalia and anus
* Inferior to pelvic diaphragm
* Underlying bony structures
* Pubic symphysis (anterior)
* Pubic ramus
* Ischial tuberosity (lateral)
* Sacrotuberous ligament
* Coccyx (posterior)
* Divisions:
* Urogenital triangle: anterior containing external genitalia
* Perineal membrane (tough, deep fascia) seals the urogenital hiatus
* Deep perineal pouch: space superficial to perineal membrane
(between levator ani and perineal membrane)
* Superficial perineal pouch: between perineal membrane and
superficial fascia - contains root and crus of clitoris/penis
* Anal triangle: posterior, containing anus
* Perineal membrane/central tendon: musculofibrous structure that anchors
many muscles in pelvic region and provides support for pelvic organs
Ligaments in female pelvis
* Ovarian ligament: anchors ovary to uterus medially (fibrous connective tissue)
* Suspensory ligament: peritoneal fold that attaches ovary to lateral pelvic brim
* Contains ovarian artery, ovarian vein, ovarian nerve plexus and lymphatic
vessels
* Broad ligament: broad sheet of pelvic peritoneum extending bilaterally from
lateral pelvis to uterus in midline - folds over fallopian tubes and ovaries and
covers them both anteriorly and posteriorly
* Mesovarium: surrounds ovary (but doesn’t cover surface of ovary)
* Mesosalpinx: wraps around the fallopian tube
* Mesometrium: largest section - relates to the uterus
* Round ligament: follows same path as vas deferens in males - vanishes within
internal ring of inguinal canal
* Medial side of ring marked by 2 inferior epigastric vessels
Uterus
* Location: inverted triangular uterine cavity between bladder and rectum
* Function: site of implantation of fertilised ovum and location of development of
foetus
* 4 parts: fundus, body, isthmus and cervix
* Uterine cavity and cervical canal separated by internal os
* Cervical canal separated from vagina by external os
* Ligaments: round and broad, pubocervical, uterosacral and transverse cervical
* 3 layers:
* Endometrium: pale inner mucosal layer where fertilised egg implants
* Myometrium: smooth muscle layer - hypertrophies during pregnancy
* Perimetrium: same layer as rest of visceral peritoneum
* Has posterior and anterior layer - together these layers form the
mesometrium
* Rectrouterine Pouch of Douglas: lowest portion of peritoneum (between uterus
and rectum) - fluid can accumulate here in trauma
* Positions:
* Anteflexion/retroflexion (angle between uterine body and cervix) - knuckles
* Anteversion/retroversion (angle between cervix and vagina) - wrist
* Pregnancy: fundal height - if too low, there may be intrauterine growth retardation
* 12 weeks: pubic symphysis
* 20 weeks: umbilicus
* 36 weeks: xiphoid process
Fallopian tubes
* Function: transport secondary oocyte to uterus for fertilisation (contains smooth muscles that propel ovum
towards uterus)
* 4 parts:
* Infundibulum (distal): contains fimbriae (finger-like projections) that open into peritoneal cavity via
abdominal ostium
* Ampulla: enlarged part of tube just past the infundibulum
* Isthmus: thinner area of tube that opens into ovarian cavity
* Clinical significance:
* Pelvic inflammatory disease (PID): pathogens can spread retrogradely from vagina to peritoneal cavity → pelvic peritonitis or general peritonitis
* Endometriosis: retrograde menstruation (blood flow backwards into pelvis) - endometrial tissues grow on peritoneal surface of pelvic organs
* Bilateral tubal ligation: permanent birth control
* Ectopic pregnancy: embryo implants within fallopian tube - muscle layer so thin, that can burst open and cause major bleed (obstetric emergency)
* Uterosalpingogram: pelvic X-Ray with cannula through vagina giving radiopaque contrast
* Vulva → vagina → cervical canal → uterine cavity → fallopian tube → peritoneal cavity
* Allows ovum to be transported into fallopian tube for fertilisation
Ovaries
* Female gonad
* Almond-shaped and not covered by peritoneum
* Functions:
* Produce secondary oocytes
* Secrete female sex hormones (progesterone,
oestrogen)
* Ligaments: ovarian, suspensory
* Ovaries change texture with age
* Young people who haven’t released many eggs
look pink
* Advanced age at end of productive life - scarred
surface that looks white
Vagina
* Location: from uterus to vaginal vestibule
* Function: passageway for childbirth and female organ of copulation
* Structure: muscular tube continuous with uterus containing thick epithelium and no glands
* Rugae: transverse folds in vaginal walls
* Relations
* Superior: embraces cervix
* Anterior: bladder, urethra
* Posterior: rectum, anal canal
Supports for the uterus
* Pelvic diaphragm
* Levator ani: anterior part from body of pubis to ischial spine
* Puborectalis (most medial): wraps around top of rectum and
comes back like a sling
* Pubococcygeus (laterally): attaches pubis to coccyx
* Iliococcygeus (further lateral): attaches to lower part of sacrum
and coccyx
* Coccygeus: posterior part that arises from ileum and attaches to lateral
surface of sacrum
* Perineal body (central tendon): fibromuscular structure between vagina
and anal canal in perineum
* 3 ligaments: formed by condensation of pelvic fascia on upper surface of
levator ani muscles
* Transverse cervical ligament: lateral and above levator ani that
surrounds cervix
* Pubocervical ligament: behind pubis to cervix
* Sacrocervical ligament: posterior from sacrum that bypasses rectum
Uteral prolapse
* Damage to levator ani and ligaments during childbirth causes lack of support for uterus
* Pelvic fascia atrophy after menopause
Blood supply to female/(male) pelvic organs
* Abdominal aorta → ovarian arteries
* Common iliac artery
* Internal iliac (pelvis)
* Anterior division (to pelvic organs)
* Superior vesical artery → bladder
* Uterine artery → uterus
* Vaginal branch → vagina
* Tubule branch → fallopian tube
* Ovarian branch → ovary
* Mid-rectal artery → rectum
* Obturator artery → medial thigh
* External pudendal → external genitalia
* Posterior division (outer pelvis and gluteal muscles)
* Superior gluteal artery
* Inferior gluteal artery
* External iliac (lower limb)
* Anterior scrotal artery → scrotum
* Ovarian/(testicular) arteries arise from abdominal aorta (L1
level) and small contribution from uterine artery
* Ureter lies just below uterine artery (water under the
bridge)
* Ovarian/(testicular) veins drain to renal vein (left) or IVC
(right)
HI
Describe the blood supply to pelvic organs
Yr2, exam, own notes
Blood supply to female/(male) pelvic organs
* Abdominal aorta → ovarian arteries
* Common iliac artery
* Internal iliac (pelvis)
* Anterior division (to pelvic organs)
* Superior vesical artery → bladder
* Uterine artery → uterus
* Vaginal branch → vagina
* Tubule branch → fallopian tube
* Ovarian branch → ovary
* Mid-rectal artery → rectum
* Obturator artery → medial thigh
* External pudendal → external genitalia
* Posterior division (outer pelvis and gluteal muscles)
* Superior gluteal artery
* Inferior gluteal artery
* External iliac (lower limb)
* Anterior scrotal artery → scrotum
* Ovarian/(testicular) arteries arise from abdominal aorta (L1
level) and small contribution from uterine artery
* Ureter lies just below uterine artery (water under the
bridge)
* Ovarian/(testicular) veins drain to renal vein (left) or IVC
(right)
HI
Describe both the ovarian and uterine cycles
Y2, exam, own notes
Hypothalamus in ovulation
* Hypothalamus at base of brain produces Gonadotropin Releasing Hormone
(GnRH)
* GnRH secreted into special veins that connect to pituitary gland
* Pulsatile secretion 60-90 minutes from the beginning of cycle to ovulation
* Pituitary produces Follicle Stimulating Hormone (FSH) and Leutenising Hormone
(LH)
* FSH keeps follicles growing
* LH is a trigger hormone to develop a pre-ovulatory follicle and to ovulate it
* LH surge lasts ~36 hours
Ovarian cycle
1. Follicular phase: day 1 menstruation → ovulation
* Primordial follicles grow over 8 months before cycle starts
* Number of follicles recruited depends on numbers
remaining
* Follicle grows and produces fluid, forming antral space
* One follicle becomes the dominant follicle and others shrivel
up
* Primary follicle: 1° oocyte surrounded by Theca and
granulosa cells
* Theca cells: bind LH and secrete androstenedione
* Granulosa cells: binds FSH and produce aromatase to
convert androstenedione to estradiol
* Increased oestrogen serves as –ve feedback to pituitary (↓
FSH release)
* Without FSH, some follicles die off
* Dominant (Graafian) follicle continues to grow
2. Ovulation:
* Oestrogen levels peak toward end of follicular phase,
stimulating anterior pituitary (+ve feedback)
* Growing follicle is ~20mm size
* LH/FSH surge
* Follicle releases proteolytic enzymes that degrade
follicular tissue
* ~36 hours after surge, 2° oocyte leaves ruptured follicle
3. Luteal phase (~14 days)
* Follicle folds inward on itself, forming corpus luteum
* Produces oestrogen and progesterone
* Proliferation of endometrium
* Inhibit FSH/LH secretion so no new follicles develop
* Oestrogen levels throughout cycle:
* 100 on day 1
* 300 on day 5
* 600-700 on day 10
* 1000 day 14
Menstrual cycle
* Monthly cyclical changes in secretion of female hormones with corresponding changes in ovaries, uterus and other sexual organs
* During reproductive years of females: menarche to menopause
* Cycle results in:
* Ovulation
* Preparation of uterus for implantation
* Menstruation
* ~28 days (21-35)
Normal cycle
* First meiotic division occurs in embryogenesis
* 500 000 primordial follicles at birth in each ovary waiting for second meiotic division → meiosis II takes place after sperm entry
* Ovarian cycle: production of ovarian hormones and release of mature ovum (after growth of follicles) - follicular → luteal
* Follicular phase: before ovulation (day 1-14)
* Luteal phase: after ovulation (day 14-28)
* Endometrial cycle: preparation for implantation, menses - menstrual → proliferative → secretory
* Menstrual phase: before ovulation (day 1-5)
* Proliferative phase: before ovulation (day 5-14)
* Secretory phase: post ovulation (day 14-28)
* First half of cycle is more variable between women - most women then have predictable 14 days after ovulation (before menstruation)
Oestrogen and progesterone
* Oestrogen: greatest effect 1st half of cycle - proliferation
* Causes marked proliferation of:
* Endometrial stroma
* Endometrial glands → sustain fertilised ovum
* Other effects
* External female sex organs: maturation at puberty,
pubic hair
* Fallopian tubes: ↑ number and motility of cilia
* Breasts: growth of ducts and storm, fat deposition
* Skeleton: inhibits bone breakdown, stimulates bone
growth, epiphyseal fusion
* Oestrogen receptor deficiencies cause very long
limbs as epiphyses don’t fuse
* Skin: softer, more vascular
* Progesterone: greatest effect in 2nd half of cycle - secretion
and inhibition of proliferation
* Promotes secretory changes in endometrium:
* Prepares the uterus for implantation
* Nourishes fertilised ovum
* Inhibits FSH production
* Prevents other follicles from developing
* Other effects
* Uterus: decreases frequency/intensity of uterine contractions (prevents expulsion of implanted ovum in early pregnancy)
* Fallopian tubes: promotes secretions necessary for nutrition and movement of fertilised ovum within tubule
* Breasts: promotes development of lobules and alveoli, causing swelling
* Balance is important - unopposed oestrogen can result in endometrial hyperplasia → endometrial carcinoma
* Too much/too little of either can cause:
* Infertility (principle exploited in contraception)
* Dysfunctional uterine bleeding (heavy, excessive)
Ovarian cycle
* Follicular phase (day 5-14)
* FSH triggers follicle recruitment and growth (a few follicles grow each cycle)
* Granulosa and Theca cells of primary follicles produce oestrogen (estradiol)
* Oestrogen ↑ follicular expression of FSH receptors leading to ↑ growth
* FSH and oestrogen together ↑ LH receptors → increased sensitivity to LH
* Peak in oestrogen triggers LH release (+ve feedback)
* Ovulation (day 14)
* LH surge triggers ovulation (best hormone to indicate fertility)
* Follicular capsule ruptures (action of enzymes and prostaglandin)
* Ovum released - some females experience mid-cycle Mittelsmertsch (Ovulation
pain)
* Pain can mimic peritonitis as ~5cm follicle ruptures and spills blood/fluid into
peritoneal cavity, irritating peritoneum
* Remaining follicular capsule involutes, forming the corpus luteum
* Basal body temperature rises
* Egg caught by fimbriae of fallopian tube
* Luteal phase (day 14-28)
* Remaining cells become corpus luteum - produces progesterone and some oestrogen
* Prepares endometrium for implantation
* Inhibits further FSH production
* Endocrine organ to support early pregnancy (first 8 weeks)
* Pathology: corpus luteum failure can cause early pregnancy loss in some patients
* In absence of fertilisation, corpus luteum degenerates
* Progesterone production ceases so uterine wall is sloughed off (menses)
* FSH production also resumes
Endometrial cycle
* Proliferative phase (day 5-14) - regeneration
* Purpose: to rebuild lost endometrium in response to oestrogen
* More variable between women (accounts for variation in cycle length
between women)
* Endometrium is desquamated at menstruation, leaving only a thin basal
regenerative layer with small glands
* Increasing oestrogen from ovarian follicles leads to stromal and epithelial
proliferation with gland and blood vessel formation
* Tubular, non-secretory glands become progressively coiled
* Cellular endometrial stroma become progressively oedematous
* Mitotic activity in glands and stroma disappears by ovulation
* Glands produce mucus, which lines cervical canal
* Ovulation (day 14)
* Following ovulation, endometrium prepares for implantation
* Begins to secrete nutrient-rich substance in preparation for fertilised ovum
(nourishes fertilised ovum)
* Early sing of ovulation in epithelium is sub-nuclear vacuolisation 2-3
days post-ovulation (endometrial biopsy shows piano keys)
* Vacuoles migrate to luminal surface of endometrial epithelial cells
and are secreted → beginning of secretory phase
* Secretory phase (day 14-28)
* Purpose: nourish implanted blastocyst until placentation is complete in
response to progesterone
* Blastocyst munches on glandular secretions and swollen endometrial
stromal glands filled with nutrients
* Near constant 14 day length between women
* Accurate dating possible histologically (post-ovulatory day 1, 2, 3, etc.)
* Progesterone and oestrogen (from corpus luteum) cause continued cellular proliferation
* Endometrium (glands and stroma) measures up to 5-6mm thick
* Absence of mitotic activity
* Glands: cells are rich in glycogen and lipid - appear tortuous
* Subnuclear vacuoles → supranuclear vacuoles → discharge mucous into lumen → secretions disappear (secretory exhaustion)
* Endometrial stromal cells: increased cytoplasm in stroma so cells appear swollen and paler - swell with nutrients (pseudodecidua)
* Decidua: endometrium of pregnancy - more exaggerated changes due to high progesterone secreted from corpus luteum
* Arias stella reaction (hypersecretory glands) and decidualised stroma (plump nutrient-rich stromal cells)
* Spiral arterioles: progressively spiral/visible toward end of cycle - these are hormone-responsive, so eventually spasm causing ischaemic sloughing
* Trophoblastic cells on surface of fertilised ovum digest endometrium, absorbing stored nutrients
Menstruation
* If ovum not fertilised:
* Corpus luteum involutes
* Progesterone and oestrogen secretion drops
* Drop in oestrogen → vasospasm of
tortuous spiral arterioles → ↓ blood
nutrient/supply to endometrium →
ischaemia and necrosis
* Apoptotic bodies visible in basal
layer of glands as tiny dark dots
with pale halos
* Karyolysis (nuclear fading),
pykenosis (nuclear shrinkage) and karyorrhexis (nuclear
fragmentation) visible
* Degeneration of functional surface layer of endometrium with
sloughing
* Blue balls = balls of dead endometrium
* Uterine contractions expel endometrium, along with fibrinolysin to
prevent clotting
MED
Describe oogenesis
Oogenesis
* Begins before birth and completes after puberty¬
* Oogonia: primordial germ cells that proliferate by mitosis to generate ~7 million
by 20 weeks gestation
* Cell death results in ~2 million cells
* Primary oocyte: oogonia enlarge and begin meiosis I but arrest in prophase I
until reproductive cycles begin at puberty (no 1° oocytes form after birth)
* Primordial follicle: primary oocyte surrounded by layer of flattened
follicular cells
* Primary follicle: at puberty, primary oocyte enlarges and follicular cells plump
up to columnar cells
* Secondary oocyte: 36-38 hours before ovulation (day 14/28), LH surge causes
1° oocyte to complete meiosis I
* 15-20 primary oocytes mature each month, but only 1 reaches full
maturation to become an oocyte
* Polar body produced with much less cytoplasm (discards extra haploid set
of chromosomes)
* Ovulation: second meiotic division begins and stops at metaphase II
* Mature oocyte: at fertilisation, second meiotic division completes forming a
23X gamete
* Second polar body formed
List the anterior pituitary hormones
Anterior pituitary hormones
* Thyroid stimulating hormone (TSH)
* Adrenocorticotrophic hormone (ACTH)
* Luteinising hormone (LH)
* Follicle stimulating hormone (FSH)
* Prolactin/dopamine
* Growth hormone (GH)
Follicle Stimulating Hormone (FSH)
* Secreted in response to pulsatile GnRH
* Regulation of gametogenesis
* Males
* Sertoli cells: development of spermatozoa
* Inhibited by inhibin from testes
* Females
* Granulosa cell of ovarian follicle (menstrual cycle)
Luteinising hormone (LH)
* Secreted in response to pulsatile GnRH
* Males
* Leydig/interstitial cells: testosterone
* Inhibited by testosterone
* Females
* Interstitial cells: oestrogen, androgens, progestins
* Inhibited by oestrogen
MED
Describe the histology of the ovaries and uterus
Exam and own notes
histology of ovaries and uterus
Ovary histology
* Ovarian stroma: developing oocytes and follicles at different
stages of development
* Sex chord stromal cells
* Granulosa cells: rounded nuclei
* Theca cells: more ovoid/spindled nuclei
* Oocyte: largest cell in human body - nucleus and enormous
cytoplasm
* Graafian/mature follicle: oocyte is only one cell within follicle
* Antrum: oestrogen/progesterone-rich fluid that makes up
majority of follicle
Uterus histology
* Myometrium: smooth muscle thickness of uterine wall
* Bundles of smooth muscle fibres with pencil-shaped elongated nuclei
* Pink cytoplasm due to actin filaments
* Plentiful mitochondria
* Muscles organised into fascicles/bundles which intersect at right angles
* Endometrium: mucosal lining of uterus
* Endometrial glands (tubular, simple columnar epithelium) arranged within specialised
endometrial stroma (special fibroblasts which are hormone-responsive)
HIGH
Describe metformin: MoA, indications, contraindications, PK, adverse effects
YR2. Exam and own notes
Metformin is an insulin sensitiser, class of biguanides
Used to lower glucose in T1d/anti-hyperglycaemic
One of two main medications: secretagogies (sulphpnylureas), and GLP-1 related agents including DPP-4 inhibitors and GLP-1 receptor agonists; as well as acarbose (alpha-glucosidase inhibitors in gut) and SGLT2i.
Predominately absorbed from small intestine. Well absorbed, but food reduced absorption.
Rapid distribution
Does not bind plasma proteins
Excreted unchanged in urine/by kidney; no hepatic metabolim or biliary excretion
Tubular excretion is main mode of elimination
Indications: Drug of choice for T2DM. adjunct to diet and exercise to improve glycemic control in adults and paediatric patients over 10 with T2D. In combinations with DPP-4 inhibitors or SGLT2i or pioglitazone
↓ insulin resistance by modification of
glucose metabolic pathways:
* ↑ peripheral insulin sensitivity
* ↓ hepatic gluconeogenesis
* ↑ glycolysis
Contras: renal dysfunction, hypersensitivity, CCF needing drug treatment, metabolic acidosis*
- Adv Es: Gi upset (nausea, vomiting, stomach upset, diarrhea, weakness, metallic taste); hypo may occur if in combination with other anti-diabetic drugs; lactic acidosis (Dose-dependent); weight loss (may be desirable)
Describe the hypothalamus-pituitary-thyroid axis and regulation of thyroid hormone production
Regulation of thyroid and other hormone production is via HPA.
Hypothalamic-pituitary-target organ (HPO) axis
* Controlling hierarchy from hypothalamus → pituitary → target organs
* 3 target organs are themselves endocrine glands:
* Gonads (testes and ovaries): gonadotrophin (FSH/LH → O/P/T)
* Adrenal cortex: adrenocorticotropin (ACTH) → cortisol
* Thyroid gland: thyroid stimulating hormone (TSH)
* Other target organs
* Bones, tissues: growth hormone (GH) → long bone growth + anabolism
* Mammary glands: prolactin (PRL) and oxytocin
* Smooth muscle in uterus: oxytocin
* Kidney tubules: ADH → urine concentration
* Hypothalamus: neurosecretory cells produce releasing and release-inhibiting
hormones (ADH, oxytocin)
* Move down axons to axon endings → secreted from axon endings into
blood stream
* Secreted into hypophyseal portal system
* Each hypothalamic hormone stimulates or inhibits production and secretion of an anterior pituitary hormone
* Anterior pituitary secretes hormones into bloodstream
HI
Provide examples of commensal vaginal flora and how they protect the tract - lactobacillus
Lactobacilli
- Key characteristics of the genus:
- Gram positive bacilii
- Anaerobic - obligate anaerobe to aerotolerant
- Aciduric or acidophilic: grow over pH range 3-7
- Mesophilic: grow over 15-45 C
- Fermentation of simple carbohydrates to lactic acid (homofermentative), formic acid, acetic acid, carbon dioxide and alcohol (heterofermentative)
- Part of commensal flora of vagina, oral cavity, and gastrointestinal tract
- Rarely associated with invasive infection and disease
- Decreases in numbers of lactobacilli in vagina are associated with development of:
- vaginal candidiasis
- bacterial vaginosis
HI
Provide examples of commensal vaginal flora and how they protect the tract - vaginal candidiasis
Overview
- Most commonly caused by Candida albicans
- Part of commensal microflora of skin, mouth, GI tract and urogenital tract of healthy individuals
- Potential for systemic mycoses in immunocompromised individuals, as well as part of healthcare associated bloodstream infections
- Also commonly causes superficial, cutaneous and mucocutaneous infections including vulvovaginitis and vaginitis
- Two forms: budding yeast which undergoes asexual reproduction and pseudo hyphae which is the growth form
- Vulvovaginal candidiasis results when Candida sp. increases in numbers or overgrows. Contributing factors include:
- recent antibiotic therapy
- pregnancy
- hormones e.g. oral contraceptives or HRT
- diabetes (uncontrolled – sugars)
Symptoms, diagnosis and treatment
- Symptoms: inflammation, burning, itching and ‘cheesy’ discharge
- Diagnosis: based on symptoms/signs and/or microscopy and culture
- Treatment: change reversible factors, topical (cream, powder, pessary) or oral antifungal agents
- Can be recalcitrant in some people, therefore need to address underlying cause
HI
Provide examples of commensal flora - bacterial vaginosis
Overview
- Non-inflammatory nature
- Poorly understood pathophysiology
- Results with in Gram-variable anaerobes, e.g., Gardnerella vaginalis numbers aka overgrowth. Contributing factors include:
- decrease or change in Lactobacillus populations
- onset of menses
- use of vaginal medications or medications
- use of spermicides
- increased number or frequency of sexual partners, or new sexual partner (but it is not an STI)
Symptoms and Diagnosis
- Excessive, grey, watery, malodorous discharge resulting from metabolic activities of anaerobes, may be implicated in irritation
- Pre laboratory test: vaginal swab
- pH > 4.5
- Whiff test: fishy odour when 10% KOH added
- Microscopy shows:
- loss of lactobacilli
- increase in gram variable coccobacilli
- clue cells: squamous cells coated with bacteria
Treatment
- metronidazole:
- nitroimidazole drug
- used against anaerobic bacteria and protozoal infections
- alters or breaks down DNA (NA inhibitor)
- clindamycin
- macrolide
- inhibits protein synthesis by binding to 5os rRNA subunit
HI
Provide examples of commensal vaginal flora and how they protect the tract - neonatal infections
Fetal/Neonatal Infections
Routes of Infection
- Infections of the fetus or neonate can occur via:
- Haematogenous dissemination: from the ability of a pathogen to overcome the maternal: fetal placental barriers
- Direct infection by endogenous or exogenous pathogens
- Ascending (intrauterine) infection: infection of the aminotic membranes and fluid, which is inhaled by the foetus
- Exposure during passage through the birth canal
Neonatal Infections During Vaginal Delivery
- Neonatal candidiasis (mainly mucocutaneous)
- Herpes simplex virus (severe disseminated infection)
- Chlamydia trachomatis & Neisseria gonorrhoeae (pneumonia/conjunctivitis)
- Group B Streptococcus (GBS) – Streptococcus agalactiae (bacteraemia, pneumonia, meningitis)
- Screening for GBS in pregnant women at about 36 weeks
- Prophylactic antibiotics (penicillin) administration immediately prior to delivery if culture is positive OR regardless, if risk factors are present
- Usually does not cause symptoms in the woman, but may be implicated in vaginitis or pp-endometritis or puerperal sepsis
Review – Group B Streptococci
- Gram stain appearance
- Meaning of “Group B”
- Haemolysis on blood agar
- Normal locations of GBS
Neonatal Infections - Group B Streptococcus
- Commensal microflora of the gastrointestinal tract and vagina.
- Found in 20-30% of healthy women
- Common cause of neonatal septicaemia and meningitis (50-70% of neonates born to women with GBS will become colonised)
- Early and late onset infections within 7 days (median 6-8 hours) and 7 months of birth respectively
- Associated with opportunistic adult infections: skin, soft tissue, urinary tract and bacteraemia
- GBS colonization in the maternal vagina/bowel by binding to various materials and foetal/neonatal cells (Respiratory, blood-brain endothelium)
- Ascending infection leading to various outcomes (invasive = traverses placental membranes):
- miscarriage
- foetal death in utero
- preterm birth (due to rupture)
- Infection during vaginal delivery causing :
- Bacteraemia
- Pneumonia (because of access to foetal lungs via aspiration or infected amniotic fluid or neonatal lungs due to aspiration of vaginal fluid during delivery)
- Meningitis
HI
Describe testing for endogenous infections
YR2, EXam and own notes
- Vulvovaginitis (skin rather than mucous membranes): Candida sp, S. Aureus, GAS/GBS
- Vulvovaginal swab MCS
- Vaginal discharge/vaginitis: Candida sp, bacterial vaginosis, GBS
- Vaginal swab MCS
- PID: mixed flora - coliform, anaerobes, Streptococci
- Cervical swab MCS - hard to access site where infection is occurring
- Asymptomatic pregnancy screen: GBS
- Vaginal swab MCS
MED
Describe vaginal swab
OWn notes
Vaginal Swab Culture
- Depends on clinical history
- “Standard”
- Chocolate and gonococcus specific plate
- Note that cervical swab is specimen of choice for gonococcus
- “Candidiasis”
- Add a Sabouraud plate (selective yeast agar)
- “Pregnancy Group B Streptococcus screening”
- Specialised broth and agar
- “Post partum/gynaecological surgery/PID”
- Add an anaerobic plate
A standard swab:
- normal vaginal flora will mainly contain lactobacilli but also small amounts of other micro-organisms e.g. coliforms, GAS and S. aureus
- The lab is mainly looking for a change in the normal flora and a predominance of an organism which may be pathogenic
- this is a split plate
- chocolate agar is on the left, specialised gonococcus agar ison the right
- the gonococcus agar has inhibitors to stop growth of other organisms, as well as nutrients to support N. gonorrhoeae
- IF gonorrhoeae is suspected, a cervical swab is the specimen of choice
Vaginal Candidiasis
- Culture on Sabouraud agar: contains antibiotics to inhibit bacteria and nutrients to support fungi
- If request queries Candida or yeast seen on microscopy
### Group B Streptococcus Screening in Pregnancy
- Normal vaginal carriage of GBS causes no symptoms in the woman
- we are looking for any evidence of GBS, therefore we need to maximise our chances of finding it
- swab is placed in enrichment broth to encourage growth
- specialised media is used to grow and identify GBS
MED
Describe the factors that determine the composition of the microflora
EXAM, own notes
MICROBIOLOGY OF FGT
Key factors determining composition of microflora
* Local defences
- Cervical mucociliary escalator: helps prevent
endogenous and exogenous microbes of LGT reaching uterus and sterile UGT
- Cervical mucus:
- Contains antimicrobial proteins e.g. lysozyme, lactoferrin, IgA
- Protects cell receptors from microbial adhesions
- Serves as source of microbial nutrients
- Temperature
- pH: affected by age and hormones ∴ fluctuates during lifetime and throughout menstrual cycle/pregnancy
- Neutral pre-menarche
- Varies monthly post-menarche
- Remains acidic during pregnancy
- Neutral post-menopause
- Availability of oxygen (aerobic) or lack of oxygen (aerobic)
- Microaerophilic - oxygen availability typically ~2% of that found in air (favours anaerobic organisms)
- Affected by:
- Hormones - most anaerobic mid-cycle
- Tampon
- Contraceptives
- Sources of energy and nutrients for microorganisms
- Mucus: mucins, proteins, organic and inorganic
compounds - Vaginal fluid: rich source of protein/AAs, carbohydrate,
lipids, inorganic ions - Menstrual fluid: various nutrients, including iron
- Glycogen: present only in reproductive years
- Obtained by microbes from desquamated (dead)
epithelial cells - Very important energy source lactobacilli
- Sexual fluids
- Metabolites produced by other members of the commensal microflora
HI
List the common causes of female and male infertility
Female infertility
* Ovulatory disorders
* PCOS (ovaries have oocytes but not releasing eggs)
* Intensive athletes suppress hypothalamus → amenorrhea
* Anatomical problems
* Fallopian tube occlusion due to Hx of PID, previous ruptured
appendicitis
* Endometriosis - can cause anatomical distortion
* Sexual dysfunction
* Vaginismus
* Dyspareunia - penetration painful so can’t have intercourse
* Lifestyle factors
Male infertility
Sperm count:
* Azoospermia: no sperm
* Oligospermia: low sperm numbers
Sperm quality:
- Asthenospermia: poor sperm motility
- Teratospermia: poor sperm morphology
* Anti-sperm antibody
- Particularly if Hx of insult/surgery (vasectomy, vasectomy reversal, hernia removal) has broken the blood-testis barrier
* Sexual dysfunction (psychological, medication-induced) e.g. erection and ejaculation
* Lifestyle factors (obesity can cause oligospermia or azoospermia due to oestradiol production from excess adipose)
HI
Describe thyroid function tests and thyroid hormone synthesis
Exams*3 * and own notes
The two most common tests check your TSH (thyroid-stimulating hormone) and T4 or free T4 (thyroxine) levels.
TSH may also be conducted.
Thyrotropin releasing hormone (TRH) → anterior pituitary → thyroid stimulating hormone (TSH) → thyroid * Secreted by thyrotrophs of anterior pituitary
* Stimulates:
* Thyroxine (T4) and triiodothyronine (T3) synthesis
* Thyroid growth
* Regulation
* Thyrotrophin releasing hormone (TRH) stimulates release
* Thyroid hormones (T3, T4) inhibit release (–ve feedback)
* Acts via cAMP
1. Iodine transport: TSH binds to receptors on follicular cells,
resulting in active transport of dietary iodide I– via Na+/I–
symporter into thyroid
* Diffuses into colloid via anion exchange protein (Pendrin)
* 2. Thyroglobulin synthesis: protein with many tyrosine AAs
that eventually become individual thyroid hormones
* 3. Thyroid peroxidase: catalyses oxidation 2I– → I2 + 2 e– in
follicular lumen
* I2 covalently linked to thyroglobulin, forming MIT (single-
iodinated) or DIT (double-iodinated)
* MIT and DIT are coupled to generate T3/T4
* 4. Endocytosis: peroxidase-processed thyroglobulin is
endocytose into the epithelial cell and combines with lysosomes
* 5. Release: thyroglobulin is broken down by lysosomes, releasing T4 and T3 which are transported out
of follicular epithelial cells into circulation
* Log linear relationship between circulating T4 and pituitary TSH - as T4 levels fall, feedback inhibition is
reduced and TSH levels rise
-low tsh indictes hyperthyroidism, or hypothyroidism occasionally if there is an abnormalitiy in the pituitary gland
-low T3 indicates hypothyroidism, or starvation
- high T3 indicates hyperthyroidism
- low T4 indicates underactive thyroid or hhypothyroidism (low T4 and TSH indicates pituitary cause)
- high T4 indicates hyperthyroidism
- low TSH but normal T4 could be mild or subclinical hypothyroidism
MED
List some reasons to repeat cervical smear
EXAM
Blood or mucous, damage intransit byeither heat or cold, improper preparation, wrong location, not enough cells, slide not labelled, absence of 2 IDiers
HI
Describe the histology and function of the thyroid
Location
The thyroid gland is located anterior to the upper part of the trachea (C5-T1).
Macroscopic appearance
The thyroid gland is butterfly shaped.
It weighs about 20g normally.
It produces T3, T4 and calcitonin.
Microscopic appearance
At low power: circular structures can be seen. These are follicles.
Follicles are filled with uniformly pink staining substance. This is colloid. Colloid contains thyroglobulin - which is the storage form of T3/T4.
At high power: a layer of thyroid epithelial cells can be seen lining each follicle.
In the interstitium are parafollicular or C cells - which cannot be seen on H and E and require IHC to be visualised. They secrete calcitonin.
Function of thyroid gland
Thyroid hormones T3 and T4 are produced from the follicles.
TSH stimulates thyroid epithelial cells, which take up colloid, leaving reabsorption droplets behind in colloid.
The epithelial cell cleaves T3 and T4 off thyroglobulin, and thus T3 and T4 are secreted. ^[can tell how active follicle is by number of reabsorption droplets on H&E]
T3 and T4 serve to increase the basal metabolic rate.
Parafollicular cells secrete calcitonin in response to increases in serum calcium concentration.
Together with PTH it regulates blood calcium levels, by inhibiting the osteoclastic resorption of bone to decrease serum calcium levels.
HI
Compare and contrast Cushing’s and Addison disease
Yr2, EXAM, own notes
Definition: Chronic ↑ glucocorticoids
Aetiology:
* 1º - Adrenal problem (ACTH Independent) à SYNDROME
* 2º - Pituitary problem (ACTH Dependent) à DISEASE
Investigations:
1) Test cortisol levels
* 24-hour urine free cortisol (↑)
* Midnight salivary cortisol (↑)
* Overnight dexamethasone suppression test (↑)
2) Serum ACTH
* ↑ - 1º hypercortisolism
* ↓ - 2º hypercortisolism
Definition: Acquired primary (1º) adrenal insufficiency
Aetiology: Autoimmune destruction of the adrenal cortex
is the primary cause
Adrenal crisis: Acute onset, severely low glucocorticoids
2º Adrenal insufficiency is commonly caused by
exogenous steroid administration leading to
suppression of ACTH synthesis
nvestigations (diagnosis):
* Morning cortisol (↓)
* ACTH (↑)
* Short synacthen test
* (synthetic ACTH)
* Test cortisol at baseline, administer synacthen, test
cortisol afterwards
* ↓ cortisol = 1º adrenal insufficiency (Addison’s)
* ↑ cortisol = 2º adrenal insufficiency (think pituitary)
Don’t forget the other adrenal hormones!!!!!
* BGL (↓)
* FBC
* EUC – Aldosterone may be deranged leading to
electrolyte disturbances (↓Na+, ↑K+ etc.)
* Renin: ↑
* Aldosterone ↓
HI
Compare and contrast Graves and Hashimoto thyroiditis
Graves and hashimotos pathophysiology:
- In both Graves disease and Hashimoto thyroiditis, thyroid-reactive T cells are formed and infiltrate the thyroid gland.
- In Graves disease, most of the T cells undergo a Th2 differentiation and activate B cells to produce TSHR antibodies, which stimulate the thyroid and cause clinical hyperthyroidism
- In contrast, Hashimoto thyroiditis is caused by Th1 switching of the thyroid-infiltrating T cells, which induces apoptosis of thyroid follicular cells and clinical hypothyroidism,
mgmt:
Surgery or metho/carbimaxole
Mgmt:
Levothyroxine and surgery
—
Features of hypothyroidism: The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, coarse hair, puffy face, hoarse voice, muscle pain. Myxoedema coma. Goiter. Slowed HR. heavy periods/fertiloty. Low mood/depression. Forgetfulness. Dry skin.
Features of hyperthyroidism:’
- weight loss despite an increased appetite
- bulging eyes
- rapid or irregular heartbeat
- nervousness, irritability, trouble sleeping, fatigue
- shaky hands, muscle weakness
- warm moist palms
- sweating or trouble tolerating heat
- frequent bowel movements
- an enlargement in the neck, called a goiter
- infertility
- scant period
- difficulty sleeping
Thyrotoxicosis:
Definition: Elevated thyroid hormones (T3/T4) leading to clinical
features of hyperthyroidism
Aetiology:
⁃ Graves disease: T-cell mediated B-cell activation leading to
production of anti-TSH-r Abs causing constitutive activation of the
TSH-r
⁃ Toxic multinodular goitre
⁃ Adenoma
⁃ Thyroiditis
Thyroid storm: severe life-threatening thyrotoxicosis causing end
organ dysfunction
MGMT: imaging, drugs, surgery (radioiodine ablation or thyroidectomy, appearance of anti-TSHR, anti-TPO, anti-Tg)
HI
Descrieb causes of pelvic inflammatory disease
Yr2, exam, own notes
Anatomical relationships
#clinicallyrelevant for two key reasons:
- pathogens can spread retrogradely from vagina to peritoneal cavity. Examples include pelvic inflammatory disease e.g. pelvic peritonitis or general peritonitis, as well as salpingitis from peritoneal infections
Spectrum of STI presentations e.g. Trichomonas, Chlamydia, Neisseria
- Asymptomatic infection
- Lower genital tract symptoms (vaginal/urethral discharge)
- Upper genital tract symptoms (pelvic inflammatory disease
HI
Describe the pathophysiology and treatment of T1DM
Yr2, exam, own notes
Type I Diabetes Mellitus
- Characterized by
- Pancreatic β cell destruction and ultimately absolute insulin deficiency
- T cell-mediated
- Presence of autoantibodies (directed against pancreatic islet cells)
- Glutamic acid decarboxylase (GAD), protein tyrosine phosphatase (IA2), zinc transporter 8 and insulin (IAA)
- Presence of one or more antibodies can precede clinical onset by many years (presence of all three close to 100% risk of developing clinical diabetes)
- No evidence that these autoantibodies are pathogenic
- Inflammatory response within the pancreatic islet cells “insulitis”
- Mononuclear cell infiltrate with predominantly CD8+ cells (CD4 + T cells and macrophages)
- observed in early diabetes
- Increased expression of Class I MHC and aberrant expression of class II MHC on beta cells
- Mononuclear cell infiltrate with predominantly CD8+ cells (CD4 + T cells and macrophages)
- Progressive pancreatic β cell destruction (size and number)
- mediated by autoreactive CD4+ T cells
- lysis by cytotoxic T cells
- local production of pro-inflammatory cytokines and ROS
- evidence for defects in Treg function
- overt diabetes only occurs once most of these cells have been destroyed
- During fasting or otherwise in the absence of insulin (type 1 diabetes), hormone-sensitive lipase in fat cells is activated.
- This results in hydrolysis of stored triglyceride into glycerol and fatty acids.
- β-oxidation of fatty acids in mitochondria results in excess formation of ketone bodies.
- Associated with this is the development of metabolic acidosis.
Investigate: plasma glucose, HBA1C, OGTT, c peptide (Bedside: Urinalysis, urine dipstick, fundoscopy, diabetic foot Ex, BP
Bloods: FBC, EUC, LFT, cholesterol studies
Special tests: Anti-GAD Ab (T1DM) – common to both
Insulin:
● Can be long-, intermediate-, or short-acting
● Common insulin regimens:
○ Basal-bolus – long-acting 1-2x a day with
fast-acting boluses before meals
○ Premixed preparations – administered
twice a day (25% short-acting, 75% long-
acting)
○ Insulin pump – constant infusion of insulin,
may be increased before meals
● Subcutaneous injection
● Requires electrolyte monitoring (esp. K+)
HI
Describe the pathophysiology and treatment of T2DM
Y2 and own notes
Clinical features:
- gradual onset
- mainly symptomatic initially
- first presentation usually complications
Common to both:
Polyuria (excessive urination, +/- glycosuria)
Polydipsia (excessive thirst, 2º to polyuria and dehydration)
Polyphagia (excessive hunger)
Fatigue, lethargy
Blurred vision
Poor wound healing
Frequent infections
Unexplained weight loss
Mgmt:
A1c target
BP target
Cholesterol
Drugs (↓ CVD risk)
Exercise + diet
T2DM:
Metformin
Sulfonylureas
DPP-4 antagonists
GLP-1 agonists
Thiazolidinediones
SGLT-2 inhibitors
A-glucosidase inhibitors
List the macro and microvascular complications of diabetes
Y2, exam and own notes
Microvascular
- Diabetic retinopathy
- Diabetic nephropathy
- Diabetic neuropathy
Macrovascular
- Diabetes is a risk factor of atherosclerosis as chronic hyperglycemia creates a dysfunctional epithelium = impaired vasodilation, oxidative stress, pro-coagulative state and pro-inflammatory state
- Major determinants are other metabolic risk factors i.e. obesity, dyslipidemia and arterial hypertension
- Diabetics often have 1 or more of these risk factors
- Coronary artery disease - this is a major cause of death in diabetics
- Peripheral vascular disease
- Cerebrovascular disease
depending on location of atherosclerosis.
Describe diabetic retinopathy
Summary of retinopathy:
- Tends to occur in parallel to nephropathy
- Same pathways affected, particularly affecting microvasculature at back of eye
- Retinal ischaemia
- Vascular permeability (leaky vessels causing macular oedema)
- Hypertension may contribute
Proliferative diabetic retinopathy (PDR)
- Ischaemic retina releases VEGF, growth hormone, IGFR → all drive proliferative diabetic retinopathy
- New vessels (in response to VEGF) and abnormal capillaries
- Weak vessels prone to haemorrhage and fibrosis → retinal detachment → loss of vision
- Retinal flurocene angiogram shows blushes - abnormal vessel formation due to ischaemic retina
- Erythropoietin excreted in ischaemic retinopathy → retinal neovascularisation
- Treatment:
- laser to burn ischaemic parts → VEGF not produced
- Anti-VEGF injections
Non-proliferative diabetic retinopathy (NPDR)
- Cholesterol-like material (hard exudates aka dots and blots) build up on retina → leaky vessels
- Soft tissue oedema can affect central vision
- Capillary weakness → micro-aneurysms or haemorrhages from breaks in capillaries
- Important to have check ups every 2 years to exclude diabetic retinopathy - includes:
- Visual acuity test
- Retinal exam
- Better results if picked up early
Describe diabetic neuropathy
- Peripheral neuropathy: gloves and socks
- Mononeuropathy: along dermatome
- autonomic neuropathy: gut heart bladder
Summary of neuropathy:
- Peripheral neuropathy: painful feet that burn at night (doesn’t improve with diabetes control)
- Longer the nerve, the more likely it will get damaged by diabetes
- Mononeuropathy: one nerve damaged → can cause mononeuritis, multiplex or plexopathy (e.g. lumbosacral plexus affecting thigh)
- Autonomic neuropathy: postural hypotension, nocturnal diarrhoea, trouble with bladder, etc.
- Pathophysiology:
- Hyperglycaemia and glycosylation involved
- Oxidation of LDL - intracellular inflammation activated
- Increased glucose causes ROS production
- Interruption of microcirculation to single nerve e.g. diabetic CN3 palsy causing diplopia (eye goes down and out)
- Pupil sparing occurs in diabetic
- Principal treatment is to optimise glycemic control and pain management if applicable
- Also key to assess feet: sensory, motor and any deformities/calluses/ulcers/infections
- Additionally look for Charcot’s foot deformity = swollen flattened foot due to microfractures and collapse
- Lipid lowering drugs shown to help decrease all microvascular complications especially diabetic neuropathy
Describe diabetic nephropathy
Pathology:
- Glomerulosclerosis and nodular sclerosis occurs - drop out of glomeruli
- Mesangial thickening
- Gloumerular capillaries lost
- Tubules in kidneys also diseased with ↑ BM
- Some epithelial cellular changes to tubules
- Interstitial lesions and fibrosis → tubular atrophy
- Early on, hyperglycaemia causes hyperfiltration ∴ eGFR ↑ and creatinine ↓ (changes in haemodynamics of kidney tissue)
- As cellular damage occurs, eGFR ↓ → can then progress quickly to end-stage renal disease
- Microalbuminuria arises → inspirent diabetic nephropathy
- A smaller group of patients may not have albuminuria nephropathy - instead, often have hypertension → renal artery stenosis
- Contributing factors:
- Advanced glycosylation end-products (AGEs)
- Protein Kinase C activates growth factors that lead to fibrosis, inflammation and albuminuria
- High BP can contribute → ACEi and ARB antihypertensives may help
Detect with urinalysis (proteinuria, microalbuminuria in early stage and macroalbuminuria in late stage).
- Diabetic nephropathy progression:
- Stage 1 = Hyperfiltration = increase in GFR and normal albuminuria
- Stage 2 = Silent stage = Normal GFR and normal albuminuria
- Stage 3 = Incipient stage = Normal GFR and microalbuminuria
- Stage 4 = Overt stage = GFR decline and macroalbuminuria (additionally results in hypertension)
- Stage 5 = End stage renal disease = GFR <15 and macroalbuminuria (hypertension)
Comapre and contrast DKA and HHS
Y2 and own notes
The biochemical criteria for diagnosis of DKA are:
Serum glucose >11 mmol/L
Venous pH <7.3 or Bicarbonate <15 mmol/L
Presence of ketonaemia/ketonuria
Children with hyperglycaemia (Blood glucose level (BGL) >11 mmol/L) +/- ketosis who are not acidotic can be managed with subcutaneous insulin (see Diabetes mellitus, new presentation, mildly ill).
Side Effects Different types ketones produced include B-Hydroxymutyrate, acetatoacetate and acetone
Management The main aim in treating DKA is to progressively improve blood pH and clear the body of excessive ketones by aggressive fluid replacement and insulin therapy.
- Assess Airway, Breathing, Circulation
- IV Fluids - Normal Saline 0.9% NaCL (switch to 5% dextrose with 0.45% NaCl when serum glucose reaches ~15)
- Insulin - Insulin infusion until pH stabilizes
- Potassium - Administration of Insulin can cause hypokalemia, potassium levels should be checked prior to insulin administration
- ABG assessment - assess pH and need for bicarbonate
Monitoring:
Check ABG, EUC every 4hours.
Check Urine Glucose and Ketone 4hourly
Check Blood glucose hourly.
Monitor ECG for hypokalaemia/hyperkalaemia
Monitor GCS regularly
Pathophysiology of Diabetes Type II and Hyperosmolar state
Overview Hyperosmolar Hyperglycaemia (HOH) state occurring primarily in type 2 diabetes and is characterised by marked hyperglycaemia and dehydration without ketoacidosis. The disturbance in consciousness in patients varies from drowsy to comatose. HOH is a more sinister complication than ketoacidosis with a mortality rate as high as 50%.
Diagnosis - biochemical:
- Hyperglycemia
- Serum osmolality is high (>350 mmol/kg)
- No acidosis
- No ketonuria + on urine dip testing can occur with starvation and vomiting.
Serum osmolality (in mosmol/kg) can be calculated if not available from the laboratory using the following equation:
Osmolality = 2(sodium + potassium) + glucose + urea
Pathophysiology This condition results from a combination of insulin deficiency and coun- terregulatory hormone excess. The insulin present stops ketone produc- tion but in insufficient quantities to prevent worsening hyperglycemia.
Management Same as DKA, but with a few exception because patients are usually older.
- IV Fluids - Normal Saline 0.45% NaCL (switch to 5% dextrose with 0.45% NaCl when serum glucose reaches ~15)
- Insulin - Slow Insulin infusion until pH stabilizes
- Potassium - Administration of Insulin can cause hypokalemia, potassium levels should be checked.
- Antibiotics - if infection
- ABG assessment - assess pH and need for bicarbonate
HI
Describe the procedure of OGTT
EXAM, Y2, own notes
- Unrestricted carbohydrate intake in the last 3 days prior to test
- Avoid excessive exercise before test
- OGTT should not be performed on hospitalised, acutely ill or inactive patients
- Discontinue, when possible, meds known to affect glucose tolerance e.g. corticosteroids, beta-blockers, diuretics, antidepressants
- 10-14 h o/night fast the night before the test
- No cigarettes/coffee/tea
- Perform test in morning
- Patient should remain seated during test
MED
Describe tests for infertility
EXAM AND own notes
Investigations of an infertile couple ^[potential exam question]
- try and treat couple and see them together
- take full medical history from both
- family history may be relevant - genetic conditions
- consider potential impact of medicaitons on male and female fertility
- consider weight and lifestyle factors
Gynaecological history
* Menstrual cycle - how many days
* Symptoms of PCOS - oily skin, hirsutism, weight gain
* Symptoms of endometriosis - pain in periods, between periods, sex, bowel movements
* Past history of STIs
* Past obstetrics history
* Past gynaecological surgery
* Past fertility treatment
Female investigations
* Cervical screening
* Antenatal screen
* Hormone day 2: LH, FSH, prolactin, TFT, FAI ^[PCOS raised], SHBG ^[down in PCOS], testosterone ^[free fraction increases] for baseline ovarian reserve and assessment of PCOS (also rubella?)
* Day 21: estrogen, progesterone to confirm ovulation
* Antimullerian hormone
* Pelvic ultrasound for anatomical survey, tubal patency (Hycosy), antral follicle count and signs of endometriosis
* Or Hysterosalpingogram ( Xray ) for tubal patency
Male investigations
* Semen analysis: “SFA + IBT”
= Volume, concentration, motility, morphology and antisperm antibody screen
* Do not rush in to repeat semen analysis if initial abnormal, wait 12 weeks to repeat (Refer to a dedicated andrology laboratory)
* FSH, LH, testosterone, thyroid function and prolactin if oligospermia
AMH test
– Can perform anywhere in menstrual cycle
– OCP or any hormonal contraception may reduce level
– Some intra-individual variation : best to repeat if big decisions are about to be made on it
* Shall I order it?
– Will it change behaviour or management
– Careful counseling especially in single women
– What would you do if it’s normal
– What would you do if it’s abnormal
Describe and distinguish between menopause and premature ovarian failure
Menopause
- Definition: The permanent cessation of menstruation **resulting from the loss of ovarian follicular activity.
- Natural menopause is recognized after 12 consecutive months of amenorrhea, with no other obvious pathological or physiological cause.
- Median Age: ~51 years
- Menopause is a retrospective clinical diagnosis (World Health Organisation 1994)
Extra notes:
* Surgical menopause: removal of both ovaries (any age)
* Premature ovarian insufficiency (PO): cessation of ovarian function before age of 40 (↑ risk of CVD, dementia and osteoporosis)
* Permanent loss of ovarian follicular developement
* Loss of cyclical production of estradiol, progesterone and testosterone - may/may not result in symptoms
Premature Ovarian Insufficiency
- Cessation of ovarian function 2 standard deviations prior to the population mean age of menopause.
- i.e., 2 X SD prior to 51.5 years
- Practical definition: Before the age of 40 years
HI
List five forms of contraception and their advantages and disadvantages
Y2, Exam, own notes
Hormonal Contraception
- Exogenous hormone effect on endometrium:
- Stroma appears pseudodecidualised – polygonal cells with abundant eosinophilic cytoplasm with central vesicular nuclei
- COMBINED ESTROGEN/PROGESTOGEN CONTRACEPTIVES
- Prevention of ovulation is the dominant mode of action via synergistic (E + P) suppression of LH surge/ovulation and FSH (follicle development)
- e.g. COCP (combined oral contraceptive pill)
- Risks: thrombosis, HTN, vascular events (stroke/MI), liver adenoma, ?increased breast cancer/cervical cancer
- Benefits: regular, less heavy periods, acne, prevention of ovarian and endometrial cancer, ?decreased bowel cancer, decreased all-cause mortality
- PROGESTOGEN-ONLY CONTRACEPTIVES
- suppression of the LH surge and ovulation (variable efficacy)
- viscous and scant cervical mucus to deter sperm penetration
- prevention of endometrial growth and development - prevention of implanatation
- reduction in cilia motility and muscular peristalsis pereventing transport of ovum
- e.g. norplant, minipill, morning after pill, depo-provera
Progesterone Only Pill (POP) (Mini-pill)
- Levonorgestrel or norethisterone, drosperinone (long acting)
- Traditionally short-lived effect (max 27 hours). “3-hour window,” however new formulation 24 hours!
- Easy to start and stop
- Generally does not interfere with the cycle, however, drosperinone tends to cause amenorrhea
Progesterone Injection “Depo”
- Depot injection (medroxyprogesterone acetate)
- IM injection buttock (or arm)
- Every 12 weeks
- May delay return to fertility
- Lowers oestrogen – concern for low bone mineral density – older women
Progesterone “Implanon” Implant
- 3 years
- Releases etonorgestrel
- Inserted under the skin upper arm
- Spotting early on
Intrauterine Device (IUD) (Levonorgestrel) (“Mirena or Kyleena”)
- T-shaped device inserted into the uterus (by trained GP or specialist)
- 5 years
- Small amount progesterone local action, usually little in the way of side effects
- Nulliparous or parous women
n.b. Mirena higher dose, Kylena lower dose - more spotting
- Barrier protection e.g. condoms
- Stops sperm entering the vagina
- Only contraception that provides protection from STIs (some)
- Fertility Awareness
- Tracking cycle with calendar, temperature, cervical mucous…
- Avoiding fertile window
- Copper IUD
- Create toxic environment for sperm
- Prevent implantation
Sterilization
- Vasectomy - Male vas deferens are cut and tied or sealed
- Tubal ligation - clips put on the fallopian tubes
- Tubal occlusion (Essure TM) metal coils in fallopian tubes - 1999 - 2017. Recalled in late 2017 due to adverse events.
List all the anterior pituitary gland hormones, corresponding hypothalamic hormones, target organs and their function
HI
Label this diagram of the male reproductive tract
Label this diagram of the female reproductive tract
HI
Describe the effect of insulin on metabolism
Y2, exam, own notes
HI
Describe cervical cancer
Y2
Risk factors
1 - Multiple sexual partners
2 – Young age at first intercourse
3 – High parity
4 – Persistent infection of high oncogenic risk HPV
5 – Immunosuppression
6 – Certain HLA subtypes
7 – Use of OCP
8 – Use of nicotine
HPV DNA integrates into host squamous epithelial genome
HPV infects immature basal cells of squamous epithelium in areas of epithelial breaks or immature metaplasia present at squamo-columnar junction
HPV replicates in mature non-proliferating squamous cells where they re-activate mitotic cycle
Koilocyte cells appear at superficial squamous layer due to breakdown of keratin in HPV-infected cells
Perinuclear halo + nuclear enlargement
Function: HPV E6/E7 inactivate tumour suppressor genes (especially p53 and RB)
Screening:
National Cervical Screening Program
Ages 25-74, every 5 years
Person with a cervix
Have had any type of sexual contact
Pap test replaced with vaginal swab kit (self test or by clinician)
Must be accessed through a doctor even if self-test (not mailed out)
Self-test kit detects HPV
Does not require access to cervix (vaginal swab)
Describe sulfonylureas
- phased out
Describe incretins
Describe thiazolidinedione
Describe empagliflozin
Descrive a-glucosidase inhibitors
Describe calcium metabolism
- [Ca2+] in PLASMA/INTERSTITIUM is what matters
- Why? – Think about the role of Ca2+ in the
interstitium/plasma? - Muscle function – Ca2+ rapidly enters the myocyte the
enable the actin-myosin interaction to enable contraction - Nerve function – Ca2+ rapidly enters the neuron to enable
neurotransmitter release - WE NEED TO KEEP THIS WITHIN 2.20-2.55mmol/L
