Module 7 Urogenital Flashcards

Question

Positions of the uterus and cervix

Answer 1

Uterus is usually in an anteverted and anteflexed position Retroflexion and retroversion can be normal variations. In some cases endometriosis scarring can cause the uterus to be retroverted and/or retroflexed

Answer 2

Labium minus Glans clitoris Fourchette Vaginal opening Prepuce of clitoris Mons pubis Openings of lesser vestibular glands (Skene’s) Frenulum Vestibule Hymen Urethral opening Labium majus Opening for greater vestibular glands (Bartholin’s)

Answer 3

Composed of the two crura (corpora cavernosa) which join in the middle to form the body and the glans The crura attach to the ischiopubic rami The body and glans covered by the prepuce when not erect The crura communicate with the bulbs  both contain erectile tissue Innervated by the dorsal nerve of the clitoris (branch of the pudendal nerve) The clitoris and bulbs are embryologically homologous with the penis

Answer 4

The vagina is a potential space, compressed by the bladder and rectum. Rugae allow for distension of the vaginal canal. Proximal aspect surrounds the cervix creating the fornices (two lateral, one anterior, one posterior), opens distally at the vestibule

Answer 5

Cystocele - bladder Rectocele - rectum Uterine prolapse Diagnosed with digital examination Risk factors include childbirth, menopause, chronic constipation

Answer 6

Parous cervix  transverse cervical os Nulliparous cervix  circular cervical os

Answer 7

Abdominal aorta bifurcates into right and left common iliac arteries at L4 vertebral level -> Internal iliac arteries -> anterior and posterior trunks Posterior trunk does not supply pelvic viscera Iliolumbar artery Lateral sacral artery Superior gluteal artery Anterior trunk Umbilical - Usually not functional in adults – medial umbilical ligament/fold Superior vesical - Fundus of bladder, distal ureter, ductus deferens Uterine - Uterus, cervix, proximal vagina, uterine tubes, part of ovary Vaginal (inferior vesical in males) Vagina, inferior aspect of bladder Middle rectal - Middle and lower part of rectum, vagina, seminal vesicles, prostate Obturator - Adductor muscles in medial compartment of thigh Internal pudendal - Perineum, skin and muscles of anal and urogenital region, rectum and the erectile tissues of external genitalia Inferior gluteal - Muscles of gluteal region aorta ->Ovarian/ testicular (gonadal) Ovaries/ testes

Answer 8

Internal iliac artery branches: I - Iliolumbar Love - Lateral sacral Going - Gluteal (superior and inferior) Places - (internal) Pudendal In - Inferior vesical My - Middle rectal Very - Vaginal Own - Obturator Underwear - Uterine and umbilical

Answer 9

External and internal iliac lymph nodes receive most of the lymphatic fluid from the pelvic organs The uterus has extensive lymphatic drainage: Body + cervix = external iliac, internal iliac nodes Fundus = lateral aortic nodes Uterine tubes and round ligament of the uterus = lateral aortic, internal iliac, superficial inguinal nodes The ovary (and testis) drain directly to lateral aortic (para-aortic, L1/L2 vertebral level) nodes via ducts following the gonadal veins Lymph from specific areas of the vagina drains to different nodes: Proximal vagina = internal + external iliac Middle = internal iliac Distal vagina = superficial inguinal

Answer 10

Superficial inguinal nodes Superficial perineal region (e.g. superficial perineal pouch) Labia majora + minora Scrotal & penile skin + associated connective tissue Distal part of anal canal (inferior to pectinate line): remember superior to pectinate line = internal iliac nodes Uterine body via round ligament to labia Lower limb + lower abdominal wall Deep inguinal nodes Lymph from superficial nodes Clitoris, especially glans – direct drainage (same with penile glans) Superficial and deep inguinal nodes drain into the common iliac nodes

Answer 11

Sympathetic innervation: From T10-L2 lumbar splanchnic nerves via hypogastric plexi From L1-L2/3 sacral splanchnic nerves via sympathetic chain and inferior hypogastric plexus Parasympathetic innervation: From S2 – S4 pelvic splanchnic nerves via inferior hypogastric plexus Somatic innervation to pelvic floor and perineum Pudendal nerve (anterior rami of S2 – S4 spinal nerves)

Answer 12

Pelvic pain line is marked by the inferior limit of the peritoneum in the pelvic cavity Visceral afferent (sensory) nerve fibres from the organs above the pelvic pain line travel through sympathetic nerves to reach T10 – L2 spinal cord segments. Referred pain felt in lower abdomen (hypogastric/pubic region) Visceral afferent nerve fibres from below the pelvic pain line travel to S2 – S4 spinal cord segments via pelvic splanchnic nerves (parasympathetic) Referred pain felt in the perineal region

Answer 13

Uterus innervated by sympathetic (T10 – L2) nerve fibres and parasympathetic (S2 – S4) nerve fibres via the uterovaginal plexus (part of the inferior hypogastric plexus) Sympathetic nerve fibres contract smooth muscle of myometrium and cause vasoconstriction Visceral afferents from fundus and body of uterus travel to T10 – L2 spinal cord segments using the sympathetic nerves and sympathetic chain Referred pain to lower abdomen (hypogastric region) Parasympathetic nerve fibres contract smooth muscle in uterine cervix and encourage vasodilation. Visceral afferents from cervix (below pelvic pain line) travel to S2 – S4 spinal cord segments using the pelvic splanchnic nerves Referred pain to perineal region

Answer 14

Proximal vagina innervated by uterovaginal plexus Sympathetic nerve fibres travelling in the sacral splanchnic nerves (S2 – S4, branches from sacral sympathetic chain) Parasympathetic nerve fibres travelling in the pelvic splanchnic nerves (S2 – S4) Visceral afferents from proximal vagina (below pelvic pain line) travel to S2 – S4 spinal cord segments using the pelvic splanchnic nerves Referred pain felt in perineal region Distal vagina innervated by somatic motor (efferent) and somatic afferent nerve fibres in branches of the pudendal nerve (S2 – S4) Somatic afferents are much more sensitive, pain is felt inside distal vagina and not referred across the perineal region

Answer 15

usually for Caesarean section deliveries. Fast-acting but short duration -can be combined with lumbar epidural block for longer duration of anaesthesia Anaesthetic injected via lumbar puncture into subarachnoid space (intrathecal administration) at L3/L4 or L4/L5 vertebral level Complete anaesthesia below the waist including lower limbs - anaesthetic spreads widely in subarachnoid space and can even reach as high as the T4 thoracic spinal nerve roots Anaesthetic agent is heavier than CSF so patients lie in a slightly inclined position to avoid anaesthetic spreading too far superiorly Risk that CSF may leak out of subarachnoid space - severe headache

Answer 16

Lumbar epidural block commonly used for pain relief in vaginal deliveries  offers a longer duration of anaesthesia than spinal block. Anaesthetic injected via lumbar puncture into epidural space at L3/L4 or L4/L5 vertebral level Anaesthetises cervix, vagina, pelvic floor and perineal region. Patients may still perceive uterine contractions - transmitted by visceral afferents above pelvic pain line to T10 – L2 spinal cord segments. Anaesthetic spreads less extensively than in spinal block because the epidural space is filled with fat. Lower limb function less affected. Caudal epidural block at sacral hiatus (S4 vertebral level) can also be performed but is now less common

Answer 17

Pudendal nerve provides somatic innervation of the perineum (S2 – S4) Also conveys sympathetic and parasympathetic nerve fibres to perineum via its branches Pudendal nerve runs close to the ischial spine  one site for administering pudendal nerve block Anaesthetic blocks pain transmission from somatic afferents travelling via the pudendal nerve from distal vagina and the perineum to S2 – S4 spinal cord segments

Answer 18

Sympathetic input: Inhibits rectal contraction Secretion (male ejaculate - emission) Contracts internal anal sphincter Contracts internal urethral sphincter (male) Contracts smooth muscle in uterine vessels and myometrium (noradrenaline) Parasympathetic input: Rectal contraction Bladder contraction Relaxes internal anal sphincter Relaxes internal urethral sphincter (male) Contracts uterine smooth muscle, mainly in cervix (acetylcholine)

Answer 19

Breast overlies pectoralis major anteriorly, serratus anterior laterally, and part of rectus abdominis inferiorly Lies on deep fascia of pectoralis major Separated by the retromammary space Mammary glands consist of ducts and secretory lobules Condense to form 15-20 lactiferous ducts that open at the nipple

Answer 20

Fibrous connective tissue Run from clavicle and clavipectoral fascia to the dermis of the skin and fascia Provide support for the breast Abnormal tension in these ligaments causes pitting of the skin: peau d’orange

Answer 21

Most lymph (75%) from breast drains to the axillary nodes e.g. from superior and lateral breast tissue Relevant for breast cancer metastasis Axillary nodes Anterior axillary (pectoral) Posterior axillary (subscapular) Central axillary Lateral axillary (humeral) Apical axillary (subclavian) Axillary lymph node clearance (lymph node dissection) – surgical removal of nodes to prevent metastatic spread Lymph from medial breast tissue drains to parasternal nodes instead

Answer 22

Long thoracic nerve -> winging of scapula due to serratus anterior dysfunction

Answer 23

Pudendal nerve runs close to the ischial spine  one site for administering pudendal nerve block

Answer 24

Menarche: first ovarian-controlled uterine bleed Maturation of HPO axis increased oestrogen (20 sexual characteristics) Childbearing years (Menstrual cycle): Median length 28 days (21-35 considered normal) menses, menstruation (bleeding phase) Menopause/Climacteric: Oestrogen withdrawal, follicle depletion Cessation of menses Size, function of ovaries Mean age 51.4 yr

Answer 25

Ovarian cycle: Interval between successive ovulations Describes ovum maturation and release under endocrine regulation Progression of follicle  corpus luteum Follicular (1-14 days) luteal phase (15-28 days (folliculogenesis) Uterine cycle: Effects of ovarian hormones on uterus Endometrium is central Proliferative  Secretory phase; Vascular function, menses Angiogenesis

Answer 26

Oestradiol-17b produced from androstenedione and aromatase in granulosa, CL and adipose Progesterone (P4) secreted by corpus luteum Follicle Stimulating Hormone (FSH) follicle development and recruitment Luteinising Hormone (LH) maturation of dominant follicle, ovulation, maintenance of the CL Inhibins produced by ovarian granulosa cells to inhibit FSH secretion; Inhibin A during luteal phase; Inhibin B in follicular phase Anti-Mullerian Hormone (AMH) marker of ovarian reserve

Answer 27

Follicle-stimulating hormone, FSH: 28kDa glycoprotein Produced in gonadotrophs Ovarian follicle stimulation & growth Act on Sertoli cells Granulosa cells (follicle) Signal via a G-protein coupled receptor (GPCR) Luteinising hormone, LH: 28kDa glycoprotein Produced in gonadotrophs Ovulation Act on - Leydig cells - Granulosa cells (preovulatory follicle) - Corpus luteum Signal via a GPCR

Answer 28

Oestrogens (C18 steroid): Stimulate proliferation of endometrium Prepare endometrium for progesterone action Stimulate 20 sex characteristics of female Stimulate growth (ductal) of breast tissue Progesterone (C21 steroid): ‘Pro gestation’- hormone of pregnancy Prepare endometrium for implantation Stimulate decidualisation of endometrium Maintain uterus during pregnancy Stimulate growth (alveolar) of breast tissue -> Synergistic and opposing effects to oestrogen

Answer 29

Mean length 21-35 days; phasic Proliferative - oestrogen-dominated endometrial cell proliferation to prime uterus for progesterone actions Variable in duration, typically 14 days Secretory - progesterone-dominated refers to increased secretory activity of the endometrium Relatively consistent in length ~ 14 days based on corpus luteum

Answer 30

Day 1 is the first day of bleeding of the menstrual cycle Oestradiol 17b: levels peak just before the LH surge Progesterone: increases later in cycle due to corpus luteum Inhibins: Nonsteroidal effects on pituitary

Answer 31

Glandular tissue, under endocrine control, with Extensive stroma Highly vascularised network supplied by spiral arteries Distinct histological changes with phases of the menstrual cycle - Noyes criteria Columnar epithelial cell lining proliferates and degenerates in one cycle Glands extend deep into endometrial stroma Implantation occurs 6-12 days after fertilisation Window of implantation - endometrium optimally receptive to blastocyst

Answer 32

Endometrium optimally receptive to blastocyst

Answer 33

Markers of Endometrial Receptivity

Answer 34

Proliferative phase - round regular glands, stroma contains support and nutrients Secretory phase - Tortuous and twisted glands, glycogen droplets prepares for conception

Answer 35

Rapid angiogenesis and spiral artery lengthening in proliferative phase Then endometrial regression, spiral artery coiling causes resistance to blood flow resulting in endometrial hypoxia followed by tissue degeneration. Matrix metalloproteinases (MMP-8-9) from endometrial stroma and proteases from invading leukocytes during late secretory phase begin matrix degradation Mechanism - Progesterone withdrawal increases expression of cyclooxygenase 2 (COX-2) and increased prostaglandin (PGF2a) production by endometrial stromal cells and increased prostaglandin-receptor density on blood vessels  vasoconstriction (Primary dysmenorrhoea caused by PGs inducing myometrial contractions and ischaemia) Matrix metalloproteinases (MMPs) from endometrial stroma and proteases from invading leukocytes during late secretory phase begin matrix degradation and recovery Menstrual blood consists of endometrial cells, unfertilised ovum. Low viscosity blood and lacks prothrombin, thrombin, and fibrinogen that prevent clotting

Answer 36

Functionalis layer is shed. Basalis layer remains

Answer 37

Days 1-7 (Follicular/Proliferative Phase): In the absence of fertilisation, P4 and E2 levels low. Endometrium shed then regrows; menstruation Increased GnRH secretion from hypothalamus Decreased P4 and E2 levels due to CL demise → Increased levels of FSH (-ve feedback from steroids) FSH acts on ovarian follicular cells to increase E2 production Of several competing follicles, a single dominant follicle is selected; Other recruited follicles undergo atresia Endometrial glands mostly straight with evidence of mitosis Days 8-14: Dominant follicle matures with significant increase in size → Secretes more E2 from increasing number of granulosa cells → Endometrial proliferation and thickening High E2 circulating levels exceed a certain threshold, switching to +ve feedback on LH production from anterior pituitary. LH surge induced; ~24-36 h later, follicle rupture → oocyte released → OVULATION Ovum picked up by fimbriae of fallopian tube and enters oviduct Days 14-28 (Luteal/Secretory Phase): Under influence of LH, empty follicle converted into corpus luteum -secretes mostly P4 but also E2 P4 causes differentiation of endometrial glands to prepare for implantation P4 maintains endometrium; induces decidualisation High P4 levels suppress LH and FSH release Oocyte remains in oviduct If no fertilisation, CL degenerates → reduced P4 Vasoconstriction via prostaglandins (PGs), ischaemia; no vascular support for endometrium, menses Low P4/E2 levels  GnRH brake release;  FSH and cycle begins again

Answer 38

Transformation of endometrial stromal cells to decidual cells by cAMP, progesterone Secretory, glycogen-rich, lipid-rich cells Early nutrition for embryo Secrete prolactin (anterior pituitary) Decidua rich in uterine NK cells Plays a role in immune tolerance Impaired decidualisation implicated in miscarriage, endometriosis

Answer 39

Proliferative phase Under E2 influence, mucus is thin, watery, stretchy to aid sperm transport. Secretory phase Thick, impenetrable mucus Basis of contraception?

Answer 40

Spinnbarkeit: Describes property of stretch in cervical fluids with ‘ferning’ as a sign of ovulation

Answer 41

Painful periods/cramps - dysmenorrhoea - Primary – absence of underlying pelvic pathology, - Secondary – underlying pelvic pathology Ovulation pain - Mittelschmerz (middle pain’) Swelling/stretching or rupture of follicle on ovary’; bleed Premenstrual syndrome (PMS) Fluctuating hormone levels – mood swings, irritability, fatigue, Affects 75% of women at some point in their lives. Absence / Heavy / Irregular periods

Answer 42

Painful condition where endometrial tissue found outside uterus commonly e.g. ovaries, fallopian tubes, pelvic peritoneum; less common – bladder, intestinal wall; rare distant sites – brain, lungs Global incidence 10% premenopausal women ~delay of 6-7yrs in diagnosis (dyspareunia, pelvic pain) Cause of infertility; adhesions may cause bowel obstructions Bladder involvement may cause dysuria Explants remain responsive to hormonal stimulation Causes: Retrograde menstruation Inflammation, cytokines Reduced apoptosis/stem cells Angiogenesis/dissemination through lymphatics

Answer 43

Derived from uterine smooth muscle (myometrium) Hormone dependent, so will progressively enlarge and regress after menopause Most common benign tumour in females; no progression to cancer Frequently manifests with menorrhagia, sometimes with metrorrhagia Often asymptomatic but symptoms vary and all associated with the presence of a mass e.g. pelvic/back pain/pressure, feeling bloated, constipated, urinary frequency, dyspareunia. Pregnancy and infertility Leiomyomas can prevent the blastocyst attachment to the uterine wall Depending on the size and location, they may block the fallopian tubes Leiomyomas can lead to difficulties during labour, and therefore the need for a caesarean section

Answer 44

heavy: Menorrhagia Heavy > 80 ml and/or Light: Hypomenorrhoea Prolonged: Menorrhagia > 8 days too short: Polymenorrhoea Too long: Oligomenorrhoea

Answer 45

Coagulopathy Ovulatory Idiopathic (80%) Not yet classified Polyp Adenomyosis Leiomyoma Malignancy

Answer 46

Coagulopathy e.g. stop anticoagulant Ovulatory PCOS: COC Thyroid Obesity Idiopathic: bleeding Non-hormonal Hormonal

Answer 47

Remove the pathology Remove the endometrium Remove the uterus

Answer 48

Unexplained (~30%) Endometriosis Adhesions Ovarian cyst Fibroid

Answer 49

Bowel Urinary Musculoskeletal Neuropathic Psychological

Answer 50

Endometrial like tissue outside the uterine cavity

Answer 51

Non-medical: local heat – tens machine Pain killers: NSAID’s/ Paracetamol / Codeine Pain modulators: amitriptyline Nerve block

Answer 52

Induce Pseudo-pregnancy: Progestogens - POP, IUS (LNG), Depot (MPA) COC Induce Pseudo-menopause: GnRH analogues

Answer 53

50 years of age or older Familial factors Family history of breast, ovarian, or colon cancer (3x baseline risk). Personal history of breast or colon cancer Familial cancer syndrome (10%) BRCA (breast cancer) gene mutation Hereditary non-polyposis colon cancer (HNPCC), Lynch syndrome. Other potential risk factors Early menarche (younger than 12 years of age) Late menopause (older than 52 years of age) First pregnancy at older than 30 years of age Infertility, endometriosis Hormone replacement therapy.

Answer 54

Oral contraceptive (OC) use: longer duration of OC use (10+ years) reduces the risk of ovarian cancer.

Answer 55

Primary: 1- Epithelial (90%) Serous Endometrioid Clear cell Mucinous Undifferentiated (unclassified) 2- Germ Cell : primitive streak that ultimately migrated to the gonads. Teratoma (benign). Dysgerminoma Choriocarcinoma 3- Sex cord-Stromal (Originate from the stroma) Fibroma Granulosa theca cell tumour Sertoli-Leydig cell tumour Secondary / Metastatic : Often bilateral and from other tumours such as colon /stomach breast, uterus and cervix.

Answer 56

Teratomas are germ cell tumours that are composed of different cell types derived from 1 or more of the 3 germ cell layers. Cell types present may be ectodermal (e.g., skin, hair follicles), mesodermal (e.g., muscle, bone, teeth), or endodermal in origin (e.g., lung, gastrointestinal cells). These tumours are broadly differentiated into benign, well-differentiated cystic lesions (mature) and malignant, poorly differentiated solid lesions (immature). 90% are benign and occur in patients <20 years

Answer 57

Stage 1: Tumour limited to ovary. Stage 2: Involvement of other pelvic structures. Stage 3: Intra-abdominal spread beyond pelvis. Stage 4: Distant metastases

Answer 58

Abdominal symptoms: Dull abdominal pain Abdominal bloating. Dyspepsia. Constipation Urinary symptoms: An Increased Urge to urinate General symptoms of any cancer Other symptoms: Menstrual Irregularities Painful Intercourse

Answer 59

1- Patients with symptoms: Imaging: transabdominal or transvaginal ultrasound. Tumour markers: A. CA125. Human epididymis protein 4 (HE4) AFP (Alpha photo protein) for teratoma. HCG (Human Chorionic Gonadotropin) for Choriocarcinoma. CEA (Carcinoembryonic antigen) C. Chest X-ray (for metastasis) 2- Patients without symptoms but with family history: a. Refer the patient to the genetic clinic to check BRCA1/BRCA2 mutation.

Answer 60

Incidence: Dramatically reduced since introduction of screening. From most common female cancer to 13th. Types: 90% squamous carcinoma (squamous cells) 10% adenocarcinoma (glandular cells). Peak incidence: 30 years for cervical intraepithelial neoplasm (CIN), 45-50 years for invasive carcinoma (long onset). Presenting symptoms: post coital/unexpected bleeding. Dyspareunia, dysuria for more advanced cancer. Detection: cervical screening for early stages

Answer 61

Human papilloma virus (HPV) Multiple sexual partners. Smoking Multiple pregnancies Long-term use of the contraceptive pill Family history

Answer 62

The endocervix (endocervical canal) is a luminal cavity between the external os and the internal os and lined by a simple columnar epithelium that secretes mucus. The ectocervix is covered by stratified squamous epithelium. The squamocolumnar junction (SCJ) is defined as the junction between the squamous epithelium and the columnar epithelium. Its location on the cervix is variable. Age and hormonal status are the most important factors influencing location of SCJ. At birth and during premenarchal years, the SCJ is located at or very close to the external os (original SCJ). During reproductive age, the SCJ is located at variable distances from the external os. In a postmenopausal woman, the new SCJ is not visible and has receded into the endocervix.

Answer 63

Ectropion is defined as eversion onto the ectocervix of the SCJ along with large portions of replacement of columnar epithelium. “ COLUMNAR IS COMING”. Exposure of the everted columnar epithelium (ectropion) to irritation by acidic vaginal environment and progressively through a process called metaplasia the ectropion is replaced by metaplastic squamous epithelium. Transformation zone: Area between the original SCJ and the new SCJ where the columnar epithelium (ectropion) has been replaced by the new metaplastic squamous epithelium. The metaplastic squamous epithelium are vulnerable to dysplasia and neoplasia

Answer 64

Cervical intraepithelial neoplasm (CIN) stages 1-3 Nuclear atypia characterized by: nuclear enlargement, hyperchromasia (dark staining), coarse chromatin granules, and variation in nuclear size and shape and a clear zone around the nucleus indicative of HPV infection (koilocyte).

Answer 65

CIN I – mild dysplasia involves about one-third of the thickness of the epithelium. CIN II – moderate dysplasia involves about two-thirds of the thickness of the epithelium. CIN III – severe dysplasia and carcinoma in situ involves more than two-thirds of the thickness of the epithelium or the full thickness but intact basement membrane. Prognosis of CIN: 1) about half of CIN I will regress and only 20% of CIN I will progress over many years to CIN III. 2) About 20% of CIN III will become invasive carcinoma over 10 years.

Answer 66

Stage I- Cancer is confined to the cervix. Stage II- Cancer at this stage includes the cervix and uterus, but has not spread to the pelvic wall or the lower portion of the vagina. Stage III- Cancer at this stage has moved beyond the cervix and uterus to the pelvic wall or the lower portion of the vagina. Stage IV- At this stage, cancer has spread to nearby organs, such as the bladder or rectum, or it has spread to other areas of the body, such as the lungs, liver or bones. 5 year survival at: Stage I – 90% Stage II – 82% Stage III – 35% Stage IV – 10%

Answer 67

Sexually transmitted. HPV type 16 and 18 are responsible for most of cervical carcinoma.

Answer 68

Uterine carcinoma

Answer 69

Exposure to oestrogen is a key risk factor: Risk is increased with dose and time exposed a) Endogenous oestrogen –obesity – Polycystic ovary syndrome (PCOS). b) Exogenous oestrogen – Hormone replacement without progestin. – Tamoxifen (oestrogen agonist in the endometrium) Early menarche < 12 Years of age. Late menopause > 52 Years of age. Nulliparity Diabetic and hypertensive women develop endometrial cancer Previous history of breast, ovarian& colorectal Ca. Family History of endometrial Cancer

Answer 70

Bleeding – Present in 90% of all cases – 15% of patients with postmenopausal bleeding will have endometrial cancer Other Signs/Symptoms – Vaginal Discharge(80-90%) – Pelvic Pain, Pressure – Change in Bowel Habits

Answer 71

Stage1- Growth of tumour is confined to endometrium. Stage 2- Growth extend to cervix. Stage 3- Growth extends to vagina including lymph nodes. Stage 4- Growth invades rectum or bladder and structure beyond pelvis

Answer 72

Ovarian: pain + uro changes Cervical: post coital/ unexpected bleeding + dysuria, dysparunia Uterine: (postmenopausal) bleeding + pain

Answer 73

Chlamydia Gonorrhoea Syphilis

Answer 74

lice scabies

Answer 75

HIV and AIDS Genital Warts (HPV) Genital Herpes Hepatitis B and C

Answer 76

HIV and AIDS Hepatitis B and C

Answer 77

Infertility (male and female) Pelvic inflammatory disease (PID) in woman Epididymitis in men Urinary tract complications Cervical cancer Psychological impact Serious illness and death

Answer 78

Caused by Neisseria gonorrhoeae - Gram negative cocci (diplococci) Virulent factors - Pilus for cell attachment - Lipopolysaccharide (LPS) endotoxin - Capsule rendering phagocytosis resistant. - IgA protease destroy IgA1 (mucosal immunity) Clinical presentation: Symptoms develop 2-7 days after infection. Around 50% female asymptomatic: Purulent urethral / vaginal discharge Dysuria Rectal infection Neonatal gonococcal eye infection Pelvic inflammatory disease Untreated may result in infertility Diagnosis MC+S Culture swabs from infected area or discharge (kept warm in charcoal-enriched transport medium and sent to lab without delay). Nucleic Acid Amplification Test (NAAT)_urine sample Culture still vital – need antibiotics sensitivity for treatment due to multi-resistant strains

Answer 79

Caused by Chlamydia trachomatis serotypes D to K: Very small obligate intracellular bacteria, Gram negative (if stained, normally very weak) Clinical presentation Approx. Male 50%, female 70% asymptomatic If symptomatic Female Vaginal discharge, intermenstrual bleeding, deep dyspareunia, lower abdominal pain or discomfort Male Urethral discharge, dysuria Ocular infections in neonates infected during birth may cause blindness. Infected neonates also prone to C trachomatis pneumonia Diagnosis: Requires specialised techniques (cell culture using McCoy cell lines). Nucleic Acid Amplification Test (NAAT) Enzyme-linked Immunosorbent Assay (ELISA) Currently off the shelf test kits are available

Answer 80

Caused by Treponema pallidum (spirochete) - Gram negative (if stained, normally very weak) Motile with corkscrew motility pattern Sensitive to heat, drying ; Can not be cultured in vitro Clinical presentation - Four clinical stages of infection 1 - 10 to 90 days post infection - Small, red oral or lesions on genital, chancre (painless lesions) 2 - 2 to 10 weeks after primary stage - Brown rash on palms and soles, fever, lymphadenopathy, muscle and joint pain, hair loss in patchy pattern, rash on mucosa (mouth, throat and cervix) Latent - asymptomatic 3 - Can manifest many years after latency - Disfiguration, neuropathy, CVS abnormality, gumma (rubbery masses of tissue in organs) Diagnosis Microscopy – dark ground or immunofluorescent Can not be cultured Most commonly used serological tests RPR (Rapid plasma reagin) VDRL (Venereal Disease Reference Laboratory) TPHA (Treponema Pallidum HaemAgglutination)

Answer 81

Caused by Haemophilus ducreyi - Gram negative coccobacilli - Primarily in Africa and Asia but also becoming a sexual health issue in UK Clinical presentation Painful non-indurated genital ulcers Ulcers may look like herpes Lymphadenopathy Diagnosis MC+S Gram stain on aspirate from ulcer Culture may take 2 to 9 days

Answer 82

Caused by Herpes simplex virus Type I oral and Type II genital Clinical presentation Painful sores often blisters filled with fluid May have fever, muscle pain, malaise, itching in infected areas Treatment Symptomatic relief only If pregnant – immediate daily suppressive aciclovir

Answer 83

Caused by Human Papilloma Virus HPV over 120 types, with less than 50% homology in genome HPV 6 and 11 cause 90% genital warts HPV 16 and 18 – high risk types causing 70% cervical cancer Clinical presentation Itchy or burning lesions developing into raised lumps with characteristic cauliflower appearance Treatment: Conventionally surgical or liquid nitrogen removal, more recently thermal incision. Topical applications such as trichloroacetic acid NHS vaccines available for 12 to 18 y.o.

Answer 84

Infections by HIV does not equal AIDS (Acquired Immunodeficiency Syndrome) HIV surface glycoprotein gp120 binds CD4 CD4 lymphocytes (and other CD4 pos cells) infected Immune function ‘shut down’ due to loss of CD4 helper lymphocytes (red line on graph) – when drops to below 200 / ml Opportunistic pathogen infections may become fatal

Answer 85

Primarily Hepatitis B Can Hepatitis C be transmitted sexually? What are the transmission routes of Hep C Hepatitis C co-infection with HIV also been reported ? Other factors involved – drug use

Answer 86

Caused by Trichomonas vaginalis Both male and female approx. 50% asymptomatic Common symptom: Vaginal or urethral discharge, dysuria, vaginitis Diagnosis :Microscopy and culture both successful. Also NAAT

Answer 87

Caused by the crab louse Phthirus pubis Clinical presentation Incubation between 5 day to weeks Itch caused by hypersensitivity reaction, bites may become visible (maculae ceruleae) Eggs on hair may be visible Diagnosis Microscopy reveals adult lice and eggs Treatment As per head lice Malathion applied to dry hair and wash out Permethrin cream

Answer 88

Caused by Sarcoptes scabiei Can survive for up to 7 days Symptoms may begin 3 to 6 weeks Nocturnal pruritus Diagnosis Nocturnal pruritus Microscopy NAAT or antibody assays Treatment as per head lice Permethrin or malathion cream

Answer 89

80 to 90% caused by Candida albicans. Other Candida species also involved Vaginal discharge being main clinical presentation Microscopy reveal yeast particles sometimes with hyphae Vaginal swab culture also reveal fungal growth (pure or heavy growth. If scanty or light growth, non-significant) Although candidiasis can be transmitted sexually, most cases of candidiasis are general health issues rather than STIs

Answer 90

A core group is a sub-group within a population that has a much higher rate of STIs. An example would be the population of sex workers within a city. It is within such subpopulations that STIs are endemic.

Answer 91

A periphery group is a subpopulation that has a much lower rate of STIs than the core group. They tend to have fewer sexual partners.

Answer 92

A bridge population is a subpopulation of people withing a community that transmits an STI from a core group to a periphery group. An example would be married men who have sex with a sex worker.

Answer 93

1 Safe sex practices (e.g., the use of condoms) 2. The number of partners a person has (and time between partners) 3. Relationship between social class and seeking medical treatment for an STI

Answer 94

Someone having an STI can be stigmatised because of society’s view of the morality about sexuality.

Answer 95

Prevention: Sexual Health Services (SHSs) & condoms Education: sex education and public health campaigns Protection: partner tracing

Answer 96

Biological sex – male (XY), female (XX) Lack of Y chromosome  female SRY gene - sex determining region of the Y chromosome SRY acts via SOX-9 (transcription factor) to active genes involved in fetal testis differentiation and repressing ovarian differentiation genes Sex chromosome aneuploidies (through non-disjunction) describe conditions with loss or gain of one or more sex chromosomes

Answer 97

Prophase I

Answer 98

Primordial germ cells multiply by mitosis as they migrate After entering the ovary, oogonia undergo further expansion by mitosis At birth, ~2 million primary oocytes present ↓ Puberty ~400,000 Meiosis I begins but arrests at prophase I (primary oocytes) Meiosis I does not complete until just before ovulation several years later Secondary oocyte division arrests again at Metaphase II until fertilisation

Answer 99

Testes - Produce testosterone - Produce sperm Seminiferous tubules sites of sperm production Sertoli cell – nourish and support sperm production Sperm – undifferentiated and non-motile; transported to epididymis by contractions, for storage and become motile

Answer 100

Primordial germ cells multiply as they migrate -> enter testis (spermatogonia) and arrest in G1 After birth spermatogonia undergo expansion by mitosis in the testis giving rise to two cell types -> Type A cells are stem cells that ensure a continued pool for and Type B cells that differentiate into primary spermatocytes Meiosis begins at puberty. Completion of meiosis I gives secondary spermatocytes and meiosis II spermatids Differentiation (Spermiogenesis) then gives rise to mature spermatozoa Last stage of spermatogenesis, sperm still attached to the Sertoli (sustentacular) cells, which maintain the blood-testis barrier (tight junctions, prevent contact of sperm specific antigens and components of the immune system) Maintain high concentration of androgens, oestrogens, K+ in tubular fluid Androgen binding protein (ABP) – binds testosterone/DHT- concentrated- to enable spermatogenesis and maturation Support spermiogenesis (nutrients, etc) Secretion of anti-Mullerian hormone in the developing testis

Answer 101

Last stage of spermatogenesis, sperm still attached to the Sertoli (sustentacular) cells, which maintain the blood-testis barrier (tight junctions, prevent contact of sperm specific antigens and components of the immune system) Maintain high concentration of androgens, oestrogens, K+ in tubular fluid Androgen binding protein (ABP) – binds testosterone/DHT- concentrated- to enable spermatogenesis and maturation Support spermiogenesis (nutrients, etc) Secretion of anti-Mullerian hormone in the developing testis Golgi vesicles combine to form acrosomal vesicle Centrosomes organise microtubules in the developing flagellum Mitochondria accumulate in the midpiece Nucleus condenses and is stabilised by protamines (replace histones) for denser packing of most (~96% of genome) Excess cytoplasm is pinched off as a residual body

Answer 102

Ovulation releases the secondary oocyte and 1st polar body (with surrounding corona radiata cells). Oocyte suspended at metaphase of meiosis II Acrosomal enzymes (e.g. hyaluroidase, acrosin) break down ECM components holding corona radiata cells together. Multiple sperm are required. One sperm makes contact with the oocyte membrane - fusion triggers oocyte activation and meiosis II completes (2nd polar body ejected) Oocyte membrane depolarises and cortical reaction occurs which acts as a block to polyspermy Pronuclei and spindle fibres begin to form Pronuclei fuse (amphimixis) and the first division completes about 30 hours later

Answer 103

Inner medulla - loose areolar tissue - vessels Outer cortex - stroma & follicles Tunica Albuginea Germinal epithelium

Answer 104

3-4 wks: Primordial germ cells (PGC) - (20 – 30 cells) Migration (4 weeks): from allantois to gonadal ridge Proliferation & Differentiation into Oogonia 4 – 20 weeks: Oogonia Proliferation (Mitosis) until 20 wk -> 7 million 20 weeks: Primary Oocytes Meiosis (no further proliferation) -> 1ry oocytes Arrest at Prophase I  oocytes

Answer 105

Resting (primordial) follicles: (ovarian reserve - 7 m at 20 wk) Each 1ry Oocytes - surrounded by granulosa cells  Resting follicles (7 million at 20 weeks) Rapid Depletion of primordial follicles in-utero: From 24 weeks until birth By degeneration (90%) or entering the growth phase From 7 million at 20 wk to 2 million at birth

Answer 106

Primordial follicles: Every day, a cohort will start to grow 120 days -> primary follicle Primary follicles: 3 cycles (70 days) -> small antral follicles (2-5 mm) Small antral follicles: FSH window -> recruited into ovulatory cycle No FSH window -> atresia

Answer 107

Daily, a cohort of follicles reach FSH regulated stage If FSH < threshold -> atresia by default If FSH > threshold -> rescued FSH window: 5 days Inter-cycle FSH increased > threshold – lasts 5 days (FSH window) -> mono-follicular development Ovarian hyper-stimulation: Widening the FSH window  multi-follicular development Big increased FSH for a short period  mono-follicular development

Answer 108

Main features: [Amenorrhea - decreased FSH - decreased E2] Causes [HP failure] Hypothalamic failure: (no GnRH) Excessive exercise BMI <20 kg/m2 Eating disorders Anorexia nervosa Kalman's syndrome Pituitary failure: hypopituitarism (no FSH / LH) Congenital Sheehan Radiotherapy Trauma (surgery, fracture base of skull) Neoplasia

Answer 109

Main features: [Oligo/Amenorrhea – N FSH - N E2] Hypothalamic dysfunctions - Eating & weight disorders - Psychological - emotional 2. Ovarian Dysfunction (PCOS) obesity 4. Hyperprolactinaemia Hypothyroidism 6. Adrenal disease: CAH & Cushing

Answer 110

Main features: [Amenorrhea - Increased FSH - Decreased E2] 1 Chromosomal Mosaic Turner (45X/46XX) 2 Autoimmune 3 Ovarian Pathology - Infection - Severe endometriosis 4. Iatrogenic - Chemotherapy - Radiotherapy - Surgery 5. Idiopathic: majority

Answer 111

D21 progesterone

Answer 112

Androgen excess from Insulin resistance, or LH excess From pituitary or ovarian dysfunction Leads to: Follicular arrest in small antral phase Failure to escape atresia -> Polycystic ovary or failure to select -> anovulation

Answer 113

Short-term Reproductive Androgenic (Acne, hirsutism, baldness) Metabolic (Obesity, IGT) Long-term Diabetes (3-fold ) Cardiovascular disease (IHD, BP) Endometrial Cancer Ovarian Cancer [2-3 fold ]

Answer 114

Anovulation Oligo/Amenorrhoea/DUB Infertility Hyperandrogenism -> acne, hirsutism Insulin resistance (Obesity, IGTT)

Answer 115

Age of onset: 15 - 25 1. Oligo/amenorrhoea (85% PCOS) 2. Skin manifestations (HA) 3. Overweight / Obesity

Answer 116

Anovulation Sperm abnormality Tubal

Answer 117

Pelvic inflammatory disease

Answer 118

Low sperm count Low motility Abnormal morphology

Answer 119

Fimbria: capture the egg Cilia: unidirectional beating Peristaltic contractions Secretions: fertilisation & nourishment

Answer 120

Occlusion Proximal Distal Adhesions Kinking / distortion Disturbance of tubo-ovarian anatomy

Answer 121

Infection: PID -> occlusion & adhesions Endometriosis -> adhesions Pelvic surgery -> adhesions

Answer 122

Genetic Klienfelter syndrome, Y chromosome deletion Immotile cilia syndrome Orchitis Infective (e.g. viral) Traumatic Environmental: Smoking Alcohol Occupational Immunologic Congenital Cryptorchidism Vascular Torsion Varicocele Iatrogenic Chemotherapy Radiotherapy Antispermatogenic agents Idiopathic [90% of cases]

Answer 123

Cervical Factor Hormonal: defective response to E2 Infection: Hostile secretions Damage Immunological: anti-sperm antibodies

Answer 124

Structural defects e.g. Asherman syndrome – abnormal scar tissue Congenital septum

Answer 125

Begins in late childhood: 8-13 years for females 9-14 years for males.

Answer 126

Development of secondary sex characteristics Physical growth Sexual development Psychological development. Growth spurt Mass and fat distribution Bone maturation Adult height. Spermatogenesis (boys) / Ovulation (girls)

Answer 127

Is the activation of production of androgens by the adrenal cortex, which begins before age 8. It is responsible for appearance of pubic and auxiliary and acne (Pubarche).

Answer 128

Is the activation of the gonads by the pituitary hormones FSH and LH. It is responsible for the production of oestrogens and testosterone. Sexual maturation and development of reproductive maturity.

Answer 129

Hypothalamus releases GnRH in bursts occurring at approximately two-hour intervals. This causes rates of Follicle-stimulating hormone (FSH) and Luteinizing (LH) secretion to rise during bursts and fall between bursts. At the beginning of puberty, however, pulsatile GnRH secretion rises dramatically in response to a change in brain activity that alters neural input to the hypothalamus. (The precise nature of this change in brain activity is presently unknown) The pattern of GnRH signaling is important in determining the quantity and quality of gonadotropins secreted. The amplitude, frequency, and contour of GnRH pulses can all vary, and each of these characteristics can influence gonadotrophic responses, providing a mechanism for the differential synthesis and secretion of the two gonadotropins, LH and FSH.

Answer 130

The frequency of pulsatile gonadotropin-releasing hormone (GnRH) administration has differential effects on gonadotropin secretion: More rapid GnRH pulse frequencies favor luteinizing hormone (LH) secretion Slower pulse frequencies favor follicle-stimulating hormone (FSH)

Answer 131

Genetic Neural Control: Balance in the inhibitory and excitatory factors through coordinated changes in transsynaptic and glial-neuronal communication. Glial cells affect GnRH secretion through growth factor–dependent cell-cell signaling coordinated by numerous unrelated genes. Nutrition and Metabolic Control: Some alteration of body metabolism linked to energy metabolism may affect the CNS restraints on pubertal onset and progression. Leptin: Afferent satiety factor in humans, acting on the hypothalamus, including nuclei controlling appetite, to suppress appetite. Leptin reflects body fat and energy stores and has an important role in the control of body weight and the regulation of metabolism. Leptin increases gradually during the prepubertal years, with similar levels in the two sexes. During puberty, leptin continued to rise in girls, whereas in boys, the mean levels peaked at Tanner stage 2 and decreased to prepubertal concentrations by genital stage 5.

Answer 132

Hypogonadism (small testes) Fragile X syndrome (large testes)

Answer 133

Defined as development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys.

Answer 134

The treatment options depend upon the cause of the precocious puberty: Identifiable central nervous system (CNS) lesion, therapy is directed toward the underlying pathology. Primary treatment option is gonadotropin-releasing hormone (GnRH) antagonist which slows accelerated puberty and improves final height. Use of GnRH antagonist depends on: - child’s age - the rate of pubertal progression - height velocity - rate of bone age advancement.

Answer 135

GIPP: Gonadotropin-independent precocious Not respond to GnRH antagonist therapy. Treatment is directed at the underlying pathology. Children with tumours of the testis, adrenal gland, and ovary treated by surgery. hCG-secreting tumours combination of surgery, radiation therapy, and chemotherapy depending upon the site and histologic type.

Answer 136

Isolated manifestations of precocity without development of other signs of puberty. Premature thelarche: Transient condition of isolated breast development in the first 2 yrs. of life, often persists for 3-5 yrs., and is rarely progressive. Mostly idiopathic. Premature pubarche: Appearance of sexual hair before the age of 8 yrs. in girls or 9 yrs. in boys without other evidence of maturation. Premature menarche: Isolated vaginal bleeding in the absence of other secondary sexual characteristics. Very rare.

Answer 137

Delayed puberty is indicated if no signs of puberty are observed in a girl by 14 years and in a boy by 15 years Hypergonadotropic Hypogonadism Hypogonadotropic Hypogonadism Eugonadotropic Pubertal Delay:

Answer 138

Circulating levels of LH & FSH are high (hyper-gonadotropic hypogonadism) Congenital Turner Syndrome Klinefelter’s Syndrome Complete androgen insensitivity Acquired Chemotherapy/Radiation/Surgery Post infectious (i.e. mumps orchitis, coxsackievirus infection, dengue, shigella, malaria, varicella) Testicular torsion Autoimmune/metabolic (autoimmune polyglandular syndromes) “Vanishing Testes syndrome” “Resistant Ovaries syndrome” (gonadotropin receptor problems)

Answer 139

Constitutional Delay of Puberty Malnutrition Excessive Exercise Growth Hormone Deficiency Isolated Gonadotropin Deficiency Endocrine Causes Miscellaneous syndrome complexes Brain tumors Craniopharyngioma, astrocytoma, gliomas, histiocytosis X, germinomas, prolactinomas Iron overload (pituitary damage) GnRH receptor abnormalities

Answer 140

Congenital Anatomic Anomalies Imperforate hymen Vaginal atresia Vaginal aplasia PCOS (Polycystic ovary syndrome) Hypothyroidism Interferes with gonadotropin secretion Hyperprolactinemia Interfere with gonadotropin production

Answer 141

Male: Testosterone is usually continued until there is clear evidence of spontaneous puberty (testicular growth). The duration and dosage of therapy should be monitored by a pediatric endocrinologist as over dosage or excessively long courses can reduce the period of pubertal growth. hCG (human chorionic gonadotropin): to stimulate development of secondary sexual characteristics . Increases testicular size. Female: Testosterone is usually continued until there is clear evidence of spontaneous puberty (testicular growth). The duration and dosage of therapy should be monitored by a pediatric endocrinologist as over dosage or excessively long courses can reduce the period of pubertal growth. hCG (human chorionic gonadotropin): to stimulate development of secondary sexual characteristics . Increases testicular size.

Answer 142

First menstrual bleed Occurs near the end of Tanner stage 4 as oestradiol levels continue to rise daily High levels exert a negative feedback effect on the axis leading to cyclic oestrogen levels and uterine bleeding Positive feedback is not yet established, so ovulation rarely occurs – anovulatory Uterine bleeding regularity will vary until the hormone axis has matured and ovulatory cycles begin – can be a year or more after menarche

Answer 143

Early menarche: Abdominal type obesity Insulin resistance Glucose intolerance Cardiovascular risk Coronary heart disease Increased bone mineral density Increased cancer mortality Late: Osteoporosis Adolescent depression Social anxiety

Answer 144

Late reproductive – probability a female will conceive within a set time i.e one menstrual cycle (fecundability) reduces Early menopausal transition – menstrual cycle and endocrine changes, cycle length > 7 days from normal Late menopausal transition – ≥ 2 missed cycles and > 60 days amenorrhoea, can last 1-3 years Final menstrual period (FMP) – end of transition, cannot be confirmed until 1 year later Early postmenopause – changes in FSH and oestradiol, menopausal symptoms most likely to be seen in this time, lasts about 2 years (includes confirmation year) Middle postmenopause – stabilisation of high FSH and low oestradiol, lasts 3-6 years Late postmenopause – limited reproductive endocrine changes, stage lasts until death

Answer 145

Hot Flashes/Flushes Hallmark symptom of menopause Transient period of intense heat in upper arms and face – lasts 30-60 seconds Following by skin flushing and profuse sweating Can be followed by chills, palpitations and can lead to anxiety Often at night and can wake the woman 60-80% will experience hot flashes at some point during transition Lasts several months – 5 years (small proportion up to 30yrs) Starts during perimenopause, highest in 1st 2 years postmenopause, then decreases Negatively effect quality of life Fatigue, irritability, forgetfulness, physical discomfort Mechanisms unknown – possibly increased sympathetic nervous system drive? Hormone changes? Dry Vagina Secretions are oestrogen dependent Vaginal epithelium atrophy Less elastic, reduced blood supply Painful sexual intercourse (dyspareunia) can result Vaginal lubricants and topical oestrogens Irritation/Itchy Vulva Urinary Transition associated with stress urinary incontinence Increased urgency and frequency May be confused with urinary tract infection – antibiotics won’t help Weakness in muscle layers and ligaments of the pelvic floor - prolapse Dyspareunia Decreased desire (libido) – starts during transition phase Linked to decreased testosterone due to decreased ovarian function Decreased desire due to lower sex hormone binging globulins (SHBG) Osteoporosis CVD:Premenopause: CHD prevalence low in women (smoking main cause) Menopause transition is associated with a worsening CHD risk Change in body fat distribution – gynoid to android Higher presence of comorbid factors – metabolic syndrome, hypertension Total cholesterol increases by 10%, LDL increases by 14% Age-independent effects of menopause on cognition Short-term memory and learning shown to be affected in late transition phase (returns after menopause) Menstrual migraines peak during transition Mood swings Depression Irritability Loss of concentration …. Skin changes:Loss of elasticity – reduced collagen Dry, thinner skin Adult acne Itchy skin and formication (feeling of insects crawling) Increased hair growth

Answer 146

Premature loss of oocytes (premature ovarian insufficiency/failure) < 40 years old, amenorrhea > 4 months, x2 increased FSH Incidence: 1% <40yrs, 5% <45yrs Causes mostly unknown; familial, autoimmune, mosaic Turner syndrome, induced Loss of fertility – psychological consequences, feelings of femininity Long term effects – 2-3 fold increased risk of MI, bone loss increased

Answer 147

A medical intervention that results in menopause Occurs at any age after puberty but before natural menopause Surgical removal of ovaries (oophorectomy) often in conjunction with a hysterectomy Chemotherapy/Radiotherapy No transition period

Answer 148

Semen expelled from posterior urethra Within the vagina, onto the cervical os Coagulation – during / just after deposition Retain spermatozoa in the vagina, buffers against vaginal fluids (acidic) Coagulating enzymes (prostate derived) combine with fibrinogen-like substrate (seminal vesicle derived) Coagulum dissolves in 20-60 mins 99% still lost – vaginal leakage

Answer 149

Cervix lined by folds and crypts – spermatozoa can survive here before moving onwards Further movement dependent on phase of menstrual cycle Rising levels of oestrogen promote secretion of watery mucus Following ovulation, high levels of progesterone promote highly viscous mucus Movement through uterus – various methods Own propulsion Cervical and uterine contractions often present in preogasmic and orgasmic phases Uterine cilia action Enter uterine tube and ‘wait’ – become immotile & temporarily bind to epithelial cells Detach and re-acquire motility at ovulation: travel to ampullary-isthmic junction Dependent on chemoattractant release by oocyte and cumulus mass Sperm chemotaxis, chemokinesis (increased swimming speed) & hyperactive flagellar beating

Answer 150

Oocyte meets spermatozoa at the ampullary-isthmic junction Ampulla

Answer 151

Infundibulum of the uterine tube moves towards the ovary Fimbriated ostium envelops the ovulated oocyte with enclosing cumulus cells Cilia and smooth muscle contraction move oocyte into ampulla Meets spermatozoa at the ampullary-isthmic junction

Answer 152

Spermatozoa are not capable of fertilisation at the time of ejaculation Hyperactivated motility: increased strength and amplitude of flagellar beats Surface membrane changes: allow acrosome reaction: Removal of surface glycoproteins such as EPPIN Increased cytoplasmic pH leads to increased calcium permeability (motility) Loss of cholesterol cAMP generation leads to PKA activation and subsequently phosphorylation of tyrosine Needs to find an oocyte fairly rapidly after capacitation is complete

Answer 153

1) Cumulus cells are held together by an extracellular matrix rich in hyaluronic acid - Spermatozoal acrosome is a source of hyaluronidase – the zona pellucida is exposed 2) Spermatazoal binding to ZP3 (ZP1-4 in humans) induces the acrosomal reaction 3) Acrosome swells, and its membrane binds with the plasma membrane causing exocytosis of the acrosome contents - Inner acrosome membrane exposed 4) Proteolytic enzymes digest a path through the zona Penetration of the zona takes 5-20 mins 5) Spermatozoa enters the perivitelline space and lies along side the oocyte membrane Microvilli on the oocyte surface envelop the sperm head – bind and fuse 6) Nucleus, various mid-pieces and tail of the spermatozoa pass into the oocyte 7) Within 1-5 mins after fusion – dramatic increase in free calcium. Followed by calcium spikes (important for later events) - Cortical reaction: Calcium causes cortical granules to fuse with the oocyte membrane and release their contents Enzymes destroy ZP receptors Tyrosine residues on adjacent ZPs are cross-linked – zona becomes non-dissolvable by proteolytic enzyme Reduction in sperm-binding properties of the oolemma – mechanisms unknown 8) No additional sperm can attach to zona pellucida – prevents polyspermy

Answer 154

The oocyte has been suspended in metaphase of meiosis II since ovulation occurred Cytostatic factor stabilises M-phase promoting factor which stabilises the oocyte in M-phase Calcium inhibits cytostatic factor Meiosis II is completed and a 2nd polar body is released

Answer 155

Cytoplasmic Contributions: Spermatozoa – centriole Oocyte – pericentriolar material, cell membrane, cytoplasm, cell organelles (mitochondria)

Answer 156

Sperm nuclear membrane breaks down & highly condensed chromatin becomes filamentous strands in the oocyte cytoplasm Both sets of haploid chromosomes become surrounded by membranes – pronuclei (4-7 hrs after fusion) Both move centrally & synthesise DNA Pronuclear membranes break down & all chromosomes line up on a mitotic spindle (18-24 hrs after fusion) – syngamy Undergo anaphase & telophase A cleavage furrow forms and this leads to one-cell zygote become two-cell conceptus

Answer 157

Conceptus moves through the uterine tube to the body of the uterus Conceptus undergoes cleavage (mitotic divisions) along the way At approx. day 4 the morula stage is reached (16 cells) and the cells lose totipotency When the pre-embryo reaches the uterine cavity (~day 5) it is a blastocyst – inner cell mass and trophoblast cell wall The surrounding zona pellucida is degraded via proteolytic enzyme action – blastocyst hatches

Answer 158

Long apical microvilli, high surface charge, thick glycocalyx normally present to impair attachment

Answer 159

Stromal reaction follows attachment – primary decidualisation

Answer 160

Trophoblast cells become one of 2 types syncytiotrophoblast – cells fused together & lose cell membranes cytotrophoblast – retain cellularity, serve as a proliferative source of trophoblasts Proteases secreted by syncytiotrophoblasts break down the uterine endometrium The blastocyst invades the tissue and is eventually completely surrounded by it

Answer 161

The blastocyst produces a luteotropic factor – human chorionic gonadotrophic (hCG) Produced from approx. day 6-7 & released to pass into the maternal blood circulation hCG binds to LH receptors on luteal cells Progesterone release is maintained Progesterone also actively promotes luteal survival by autocrine stimulation – positive feedback Luteal relaxin also increased in response to hCG – linked to pregnancy-related renal and systemic vasodilation

Answer 162

Most common site of implantation is the upper posterior wall of the body of the uterus

Answer 163

Uterine tube (majority of ectopic pregnancies occur here – tubal pregnancy) Rectouterine pouch (pouch of Douglas) Intestinal mesenteries Ovary Implantation in the region of the cervical internal os: may result in placenta praevia

Answer 164

Any pregnancy implanted outside of the uterine cavity Estimated UK incidence of 1 in 90 pregnancies (RCOG) ~1/3 of ectopic pregnancies have no known cause Other causes include endometriosis, damage to the uterine tube and their ciliary lining e.g. pelvic inflammatory disease, tubal surgery Risk increases with smoking and age over 40 Symptoms include lower abdominal pain, vaginal bleeding, vomiting, diarrhoea Any patient with +ve pregnancy test and lower abdominal pain is managed as an ectopic pregnancy until proven otherwise Serum hCG concentration monitored: >50% decrease after 48 hrs suggests pregnancy is non-viable Abdominal examination: ruptured ectopic may present as pain/tenderness across abdomen Transvaginal ultrasound to visualise ectopic and any free fluid e.g. in rectouterine pouch FBC to assess current Hb levels: anaemia may indicate ruptured ectopic (haemoperitoneum) Most ectopic pregnancies diagnosed prior to rupture

Answer 165

Conservative management if stable, no evidence of free fluid, minimal pain, low or declining serum hCG Majority of tubal ectopic pregnancies are managed surgically Salpingectomy: removal of uterine tube Salpingotomy: removal of ectopic via incision in uterine tube Some trophoblast tissue may remain

Answer 166

changes in the endometrium to prepare for blastocyst implantation Progesterone causes uterine stromal cells to swell up and accumulate glycogen & lipids - decidual cells Increased vascularisation of endometrium Blastocyst triggers further decidualisation of uterine as the syncytiotrophoblast layer erodes the endometrium

Answer 167

Decidua basalis Decidual layer beneath the developing embryo Forms placenta with the trophoblast Decidua capsularis Decidual layer covering the embryo Decidua parietalis Decidual lining elsewhere in the uterus away from the embryo Decidua capsularis and parietalis ultimately fuse together as gestational sac grows and fills uterine cavity

Answer 168

Amnion (inner membrane) Lines amniotic sac and protects embryo/fetus from physical damage Secretes amniotic fluid Oligohydramnios: low volume of amniotic fluid resulting in compression of fetus Chorion (outer membrane) Formed by trophoblast and extra-embryonic mesoderm Gives rise to fetal part of placenta: chorion frondosum Embryo suspended in chorionic cavity until amniotic sac expands and obliterates this space Connecting stalk left behind – important for forming umbilical cord Yolk sac and allantois Yolk sac is an early source of embryonic nutrition Primitive yolk sac then secondary yolk sac Secondary yolk sac degenerates and its vitelline duct is incorporated into the developing midgut (Module 5) Allantois helps to form urinary bladder

Answer 169

Lines amniotic sac and protects embryo/fetus from physical damage Secretes amniotic fluid Oligohydramnios: low volume of amniotic fluid resulting in compression of fetus

Answer 170

Formed by trophoblast and extra-embryonic mesoderm Gives rise to fetal part of placenta: chorion frondosum Embryo suspended in chorionic cavity until amniotic sac expands and obliterates this space Connecting stalk left behind – important for forming umbilical cord

Answer 171

Primary chorionic villi Cells of the cytotrophoblast proliferate and grow into the syncytiotrophoblast: primitive uteroplacental circulation begins Secondary chorionic villi Extra-embryonic mesoderm grows into the core of each primary chorionic villus Tertiary chorionic villi Extra-embryonic mesoderm differentiates into blood cells and small blood vessels

Answer 172

From week 2 there is an increasing need for a circulatory system: more efficient gas and nutrient exchange Embryonic blood vessels in the tertiary chorionic villi come into contact with the intervillous spaces supplied by the maternal spiral arteries of the uterine endometrium Umbilical arteries start to form to allow deoxygenated blood to leave the embryo Umbilical vein starts to form to allow oxygenated blood to return from chorionic villi to embryo

Answer 173

Placenta formed by both the decidua basalis and chorion frondosum Basal plate of placenta = maternal decidua basalis Chorionic plate of placenta = fetal chorionic frondosum

Answer 174

Chorionic villi at embryonic pole (near umbilical cord) increase in size and number to become the chorion frondosum Chorionic villi at abembryonic pole (opposite side from umbilical cord) become the compressed and avascular chorion laeve (“smooth”)

Answer 175

Placental membrane within the intervillous spaces is the site of gas/nutrient exchange Four components at first: fetal capillary endothelium, chorionic villus connective tissue, cytotrophoblast, syncytiotrophoblast From fourth month the placental membrane thins, connective tissue and cytotrophoblast disappear Syncytiotrophoblast persists as important barrier between maternal and fetal circulations

Answer 176

One single umbilical vein that carries oxygenated blood rich in nutrients from the placenta to the fetus Two umbilical arteries that return deoxygenated blood and waste products from the fetus back to the placenta Blood vessels are enclosed and protected by Wharton’s jelly: potential source of embryonic stem cells Remnant of allantois

Answer 177

Placenta during the second half of pregnancy - purple or crimson colour, grows to around 22cm long and 2cm thick Cotyledons are lobules of the placenta which have been separated by septa (walls) from the decidua (maternal aspect of placenta)

Answer 178

Placenta praevia: placenta is too close to or blocks the internal os of the cervix Risk of haemorrhage before or during childbirth Placenta accreta: placenta grows too deep into uterine wall myometrium and strongly attaches to myometrium Risk of haemorrhage when placenta tries to detach from uterine wall during delivery Risk factors include placenta praevia, previous caesarean section, age >35 Placenta increta: even deeper attachment to myometrium Placenta percreta: placenta grows through myometrium, may attach to other pelvic structures e.g. bladder Placental abruption: early detachment of placenta from the uterus Risk of haemorrhage before or during childbirth Placental insufficiency: unable to supply enough nutrients and oxygen for fetal growth Low birth weight Risk factors include diabetes, pre-eclampsia, drug use, smoking

Answer 179

Placenta is too close to or blocks the internal os of the cervix Risk of haemorrhage before or during childbirth

Answer 180

Placenta grows too deep into uterine wall myometrium and strongly attaches to myometrium Risk of haemorrhage when placenta tries to detach from uterine wall during delivery Risk factors include placenta praevia, previous caesarean section, age >35 Subtypes: Placenta increta: even deeper attachment to myometrium Placenta percreta: placenta grows through myometrium, may attach to other pelvic structures e.g. bladder

Answer 181

Early detachment of placenta from the uterus Risk of haemorrhage before or during childbirth

Answer 182

Unable to supply enough nutrients and oxygen for fetal growth Low birth weight Risk factors include diabetes, pre-eclampsia, drug use, smoking

Answer 183

Dizygotic twins: two fertilised zygotes implant in the uterus at separate sites (non-identical twins) Each has its own placenta and fetal membranes (chorion and amnion) Monozygotic twins: zygote splits into two (identical twins) May split at two cell stage: identical twins but otherwise placenta and fetal membranes have the same arrangements as dizygotic twins Inner cell mass (embryoblast) may split: shared placenta and chorion but two separate amniotic sacs Bilaminar embryonic disc may split e.g. due to developing two primitive streaks during gastrulation: shared placenta, chorion & amniotic sac

Answer 184

If the inner cell mass (embryoblast) doesn’t separate completely, then conjoined twins may result

Answer 185

Weeks 1-12 - 1st trimester - Embryonic 13-26 - 2nd - Foetal 27-40 - 3rd - Maturation Delivery + 6 - Puerperium

Answer 186

Nausea (morning sickness) - Hyperemesis gravidarum Extreme form of nausea – treated with antiemetics, injections Amenorrhoea –missed period Breast tenderness due to increased production of steroid hormones Fatigue Food cravings ‘PICA’ – more sensitive sense of smell

Answer 187

Lack of classical, highly polymorphic MHC class I (HLA -A, -B) molecules on villous trophoblast; HLA-E, -F,-G (nonpolymorphic) and HLA-C (variable) specific expression on extravillous trophoblast Uterine natural killer (uNK) cells – most abundant leukocytes in uterus Express killer-cell immunoglobulin-like receptor (KIR) KIR binds HLA-G to reduce cytotoxic function of uNK cells. Release of ‘beneficial’ cytokines for invasion and placentation Pattern recognition receptors e.g. Toll-like receptors. T-cells: Thelper cells (Th1, Th2, Treg) = anti-inflamm

Answer 188

Prior to remodelling, low-flow, high-resistance spiral arteries have intact endothelium and a layer of VSMCs. During spiral artery remodelling, the vessel structure changes with loss of vascular cells, and this increases the size of the arteries to create a high-flow, low-resistance vessel. These changes are brought about partially by maternal immune cells (dNK cells and macrophages) and completed by invading interstitial and endovascular EVT. The remodelled vessel consists of trophoblasts embedded in a fibrinoid material as a replacement for the VSMCs, with subsequent re-endothelialisation occurring later in pregnancy.

Answer 189

Invasion of endometrium and uterine arteries by trophoblast Formation of placenta Growing fetus displaces diaphragm, heart, bladder Myometrial cells undergo hyperplasia and hypertrophy Cervix firm and non-compliant Mucus plug formed thereby maintaining closed uterine environment Measuring fundal height ( ~1cm per week)

Answer 190

1cm per week

Answer 191

Melasma/Chloasma, Linea nigra - Caused by production of melanocyte stimulating hormone by oestrogen Striae - Caused by thinning of collagen fibres and skin distension

Answer 192

300 ml/min @ 20wks 600 ml/min @ 40wks

Answer 193

Gas, fat soluble vits, anaesthetics - passive Glucose - facilitated aa, water soluble vits, ca, Fe - active transport lipoproteins, viruses, IgG - Pinocytosis

Answer 194

Oestrogen Stimulate uterine growth through endometrium/myometrium Initiates cardiovascular changes Promote ductal development in breast Effects on connective tissue Oestrogens (oestriol ~90%) Progesterone Implantation, maintenance, antagonists are abortifacients Decidualization of endometrium Progesterone (pro-gestation) Uterine quiescence Generalized relaxant effect on musculoskeletal system Respiratory changes Promotes alveolar development in breast Relaxin - Corpus luteum, decidua, trophoblast, fetal membranes - Uterine relaxation, softening Human chorionic gonadotrophin (bhCG) - Syncytiotrophoblast - Maintains corpus luteum, immune tolerance Human placental lactogen (hPL) - Syncytiotrophoblast -Breast development, inhibits maternal glucose uptake Oxytocin Posterior pituitary Uterotonic Prolactin -Anterior pituitary, decidua -Amniotic fluid genesis, osmolarity and volume, immunity

Answer 195

40-50% increase in plasma volume Increases nutrient delivery Erythrocyte number increases but less than plasma volume →Total Hb decreases overall: Haemodilution - (need for iron supplementation as demand increases) Pregnancy is a ‘hypercoagulable’ state -thrombin, fibrinogen, VII, VIII, IX, X

Answer 196

Small dip then slight rise

Answer 197

Progesterone effects via respiratory centre Little change in respiratory rate 15-20% increase in O2 consumption 40% increase in minute ventilation due to increased tidal volume. pCO2 lowered (respiratory alkalosis) but increased renal compensation through bicarbonate maintains mild alkalotic blood pH CO2 gradient helps fetus Hyperventilation Dyspnoea - combination of acid-base balance, metabolic adjustments, increased perception of discomfort on breathing

Answer 198

Enlargement in length and weight of kidneys Dilatation of ureters and of the renal pelvis Urinary stasis, raised pyelonephritis risk Renal blood flow increases (30-50%) GFR increases by ~40% Reduced serum creatinine, urea Increased tubular reabsorption of Na+ (RAAS) Glycosuria due to increased filtered load Erythropoietin for increased erythrocyte number

Answer 199

Reduced motility of GI tract Increased absorption of vital nutrients May lead to constipation Relaxed lower oesophageal sphincter (heartburn)

Answer 200

‘Show’ Mucus plug is dislodged and comes through the vagina ‘waters breaking’ Leak or flood of amniotic fluid. Regular, strong uterine contractions period pains, tightenings Cervical effacement and dilation Descent of the presenting part (fetal skull)

Answer 201

Pregnancy vs parturition Relaxation associated Proteins (RAPs) vs Contraction associated Proteins (CAPs) Progesterone, Nitric oxide, Potassium channels vs Oestrogen, Corticotropin Releasing Hormone (CRH), Oxytocin, PGE2, PGF2a, IL-1b, stretch

Answer 202

RMP of cells (myocytes) is hyperpolarised As pregnancy progresses, depolarisation Reaches threshold for Ca2+ entry Release of Ca2+ from intracellular stores Action potential generation AP complex, required for contractions Gap junctions, syncitium Phasic contraction-relaxation cycle

Answer 203

Ca2+ in, K+ out to keep hyperpolarisation After this K+ movement switches off and polarisation can occur.

Answer 204

First stage Time between onset of labour and full cervical dilatation (latent and active phase; hours long) Second stage From dilatation to delivery (<1hr) Third stage Delivery to expulsion of the placenta

Answer 205

Oxytocin - Positive Feedback Loop Uterine contractions via oxytocin -> more cervical nerve impulses when baby head pushes against it -> more oxytocin etc

Answer 206

Myometrial contractions Prelabour 10-20 mmHg; labour: 100 mmHg Contractions initiated in fundus cause shortening of muscle fibres Fetus moves further into birth canal Rupture of fetal membranes Delivery of baby followed by placenta Initiation of lactation

Answer 207

Oxytocin and prostaglandins

Answer 208

Effacement - stretching and thinning Dilatation - Cervix opens

Answer 209

Power Strength of uterine contractions and maternal efforts to expel in 2nd stage of labour Involuntary contractions that dilate and efface the cervix urge to ‘push’ by mother as fetus pushes through the maternal pelvis Passage: maternal tissues (soft: cervix, bladder, rectum) and bony pelvis. Symphisis pubis softened to relaxin Passenger: size and position (lie, presenting part) of fetus and placenta Psyche: Patients psychological state during labour, anxiety, birthing partner support etc

Answer 210

False labour pains – preparing for labour but not as a sign that labour is imminent. Do not result in cervical dilatation/effacement Start in early pregnancy but not felt until second half of pregnancy; similar to menstrual cramps BH contractions have been linked to promoting blood flow to the placenta BH contraction often irregular, of less force; change with activity. Often felt in abdomen and not like labour pain.

Answer 211

Power: hypocontractile, incoordinate contractions Passenger: fetal malposition, macrosomia, cephalopelvic disproportion Passage: Uterine abnormalities, obesity ( 1st stage) Psyche: Increasing pain, anxiety can have inhibitory effect on uterine contractility.

Answer 212

Prog and oest are low, prolactin and oxytocin inhibition finishes

Answer 213

Postpartum levels prolactin stimulated by suckling Strength and duration of suckling – raised PRL Colostrum (protein, fat-soluble vitamins, maternal IgAs, leukocytes) produced initially Mature milk rich in a-lactalbumin, lipids, lactose and vitamins B,C Lactoferrin binds iron for fetus

Answer 214

Gradual return to the non-pregnant state in ~6weeks Immediate-24hrs Uterus contracts to stop bleeding from placental site Sex steroid hormone levels dramatically reduced Uterus diminishes in size under influence of oxytocin and enzymes (collagenase, MMPs) Cardiac output/plasma volume/respiration return to normal Endometrial regeneration Oxytocin levels high if breastfeeding

Answer 215

Leading cause perinatal mortality/morbidity incidence 6-15% and rising Delivery before 37 completed weeks gestation

Answer 216

Mostly gram +ve bacteria Ureaplasma parvum Ureaplasma urealyticum Streptococci

Answer 217

Toll-like-receptors -> increased TNFa, Il-6, Il-1b .: proinflammatory

Answer 218

TOCOLYSIS –Relaxing uterus Calcium channel blockers Atosiban (OTR antagonist) Nitric oxide donors Prevention Progesterone Cervical cerclage Antibiotics Other channel modulators No proven benefits for neonatal outcome

Answer 219

Spontaneous membrane rupture before labour onset ~ 3% of pregnancies >50% women with PPROM will deliver within a week Risk of intraamniotic infection Fetal compromise caused by oligohydramnios and associated with a higher rate of CS Risk factors: Choriodecidual inflammation, uterine distension, smoking, cervical cerclage Detection/diagnosis: Positive fetal fibronectin test, short cervix Treatment: Antibiotics, antenatal corticosteroids

Answer 220

Source: Produced in between amnion and decidua

Answer 221

Cerclage, suture around cervix

Answer 222

Uterine dysfunction – incoordinate, insufficient; inadequate muscle effort in the second stage of labour – cervical effacement and dilations, fetal descent not achieved. Abnormal fetal presentation, position e.g. breech, transverse lie Abnormalities of the maternal bony pelvis e.g. cephalopelvic disproportion Poor uterine activity may be stimulated with oxytocin infusion Shoulder dystocia is more common in fetal macrosomia, diabetes, maternal obesity

Answer 223

Persistently high blood pressure arising de novo in pregnancy Hypertension – often proteinuria and/or underlying renal function Early (<34w) or late {> 34w) onset latter less severe Other symptoms: Oedema, epigastric pain, thrombocytopenia, pulmonary oedema

Answer 224

HELLP: Haemolysis, elevated liver enzymes, low platelets (thrombocytopenia)

Answer 225

Poor invasion by cytotrophoblast Poor response to vasodilators Endothelial dysfunction arteries do not dilate fully endothelial damage Risk factors: high BMI, new partner, first pregnancy, multiple pregnancy, mother/sister had PE, preexisting renal or cardiovascular disease

Answer 226

Low dose aspirin Vitamins in Pregnancy: no benefit with supplementation Magnesium sulphate for severe PE Delivery of placenta resolves PE Statins to ameliorate early onset preeclampsia

Answer 227

Failure of fetus to achieve growth potential - Growth below tenth centile May coexist with PE (early onset) Shares aetiology with PE Symmetrical (chromosomal abnormalities, congenital infections, maternal drug use) vs Asymmetrical growth (Maternal hypertension, PE, Maternal vascular disease)

Answer 228

Symmetrical (chromosomal abnormalities, congenital infections (ToRCH), maternal drug use) vs Asymmetrical growth (Maternal hypertension, PE, Maternal vascular disease, malnutrition)

Answer 229

Glucose intolerance with pregnancy onset Metformin treatment

Answer 230

Gestational Trophoblast Diseases: Molar pregnancies all arise from pregnancy where a non-viable fertilised egg implants Partial moles are triploid (2 sets paternal and 1 set maternal chromosomes) Complete moles: entirely male in origin resulting from an empty ovum (46XX by duplication of DNA of one sperm or 46XX or 46XY from two different sperm), multiple cysts form and have a ‘bunch of grapes’ appearance.

Answer 231

Encased in tunica albuginea (thick musculofascial capsule) Divided in lobules that contain seminiferous tubules Spermatozoa produced in the seminiferous tubules Spermatozoa drain into rete testis through the straight tubules Efferent ductules connect the rete testis with the head of the epididymis Epididymis has a head, body, and tail

Answer 232

Skin Dartos (from membranous layer of superficial abdominal fascia – Scarpa’s fascia) External spermatic fascia (from external oblique muscle) Cremaster muscle (from internal oblique muscle) Internal spermatic fascia (from transversalis fascia) Tunica vaginalis

Answer 233

Muscular tube carrying spermatozoa From the tail of the epididymis to the ejaculatory duct Passes through the inguinal canal Crosses the ureter Expands to form the ampulla before the ejaculatory duct

Answer 234

Forms at the deep inguinal ring Conveys structures passing between the abdominopelvic cavity and the testes Contents 3 arteries  testicular artery (from abdominal aorta), artery to ductus deferens (from superior vesical artery), cremasteric artery (from inferior epigastric artery) 3 nerves  genital branch of genitofemoral nerve, sympathetic and visceral afferents, (ilioinguinal nerve) 3 fascial coverings  internal spermatic fascia, cremasteric fascia, external spermatic fascia 3 others  ductus deferens, pampiniform plexus of veins (testicular veins), lymphatics

Answer 235

Dartos immediately deep to the skin – wrinkles the skin of the scrotum Cremaster deep to external spermatic fascia – raises the scrotum  cremasteric reflex

Answer 236

Cremasteric reflex Elevation of the scrotum and testis on the ipsilateral side after stimulation of the skin of the anteromedial thigh Mediated by the ilioinguinal nerve (sensory – ant. ramus of L1) and the genital branch of the genitofemoral nerve (motor – ant. rami of L1-L2 spinal nerves)

Answer 237

Care must be taken not to damage the ilioinguinal nerve

Answer 238

Paired glands, lie between the bladder and rectum Do not store sperm Secrete alkaline fluid containing fructose to nourish spermatozoa (~75% of semen) Alkaline fluid protects sperm from acidic environment in vagina

Answer 239

Duct of seminal glands and ductus deferens form the ejaculatory duct

Answer 240

Fibromuscular gland – contributes to semen, ~20% by volume Situated immediately inferior to the bladder, between the pubic symphysis and rectum Divided into anterior, median, and posterior lobes according to relationship with urethra and ejaculatory ducts Divided anatomically into peripheral (PZ), central (CZ), and transition zones (TZ)

Answer 241

Composed of two corpora cavernosa and a corpus spongiosum Surrounded by superficial and deep penile fascia Deep fascia and tunica albuginea help maintain erection Corpus spongiosum expands to form the glans penis containing the external urethral orifice The penile crura are attached to the pubic arch, the bulb is attached to the perineal membrane Ischiocavernosus muscles cover the penile crura (proximal parts of corpora cavernosa) Bulbospongiosus muscle covers the bulb (proximal part of corpus spongiosum)

Answer 242

Stretching of the tunica albuginea in erection increases risk of penile fractures

Answer 243

Divided into four parts: Preprostatic Prostatic Membranous Spongy Has an internal and external urethral sphincter

Answer 244

Patient in supine position If present, prepuce needs to be retracted With penis perpendicular to the abdomen, insert catheter and advance through urethra Difficulties may be encountered at the navicular fossa, angle of membranous urethra, prostate, and external and internal urethral sphincters Pulling the penis downwards can aid in advancement through the membranous and prostatic urethra

Answer 245

Patient in lithotomy position Part the labia majora and labia minora Identify external urethral meatus and insert catheter Female urethra is a relatively straight tube Difficulty may be encountered at identifying the external urethral meatus Increased risk of bladder perforation or UTIs

Answer 246

Homologous structures include: Corpora cavernosa of penis and clitoris Corpus spongiosum of penis and vestibular bulbs Ventral raphe of penis and labia minora Scrotum and labia majora Bulbourethral glands provide lubrication for the male urethra, equivalent to greater vestibular glands in females

Answer 247

Both penis and clitoris highly vascular, erectile tissues, innervated by the pudendal nerve via the dorsal nerve branch Both contain corpora cavernosa Only penis has corpus spongiosum – vestibular bulbs in females

Answer 248

Blood supply mostly from branches of the anterior trunk of the internal iliac artery Superior vesical artery: superior aspect of bladder, distal ureter, ductus deferens Inferior vesical artery (vaginal artery in females): inferior aspect of bladder, prostate Middle rectal artery: middle and lower part of rectum, seminal vesicles, prostate Internal pudendal artery: skin and muscles of anal and urogenital region, rectum below pectinate line, erectile tissues of external genitalia

Answer 249

Venous drainage largely follows the arterial supply draining to internal iliac veins Right testicular vein drains into the inferior vena cava, left testicular vein drains into the left renal vein (similar to ovarian veins) The internal iliac veins communicate with the vertebral venous plexus (VVP) via the lateral sacral veins

Answer 250

External and internal iliac lymph nodes receive most of the lymphatic fluid from the pelvic organs Ductus deferens: external iliac nodes Seminal vesicles: external and internal iliac nodes Prostate: internal iliac, sacral, obturator nodes Testes: lateral aortic (para-aortic) nodes, pre-aortic nodes

Answer 251

Superficial inguinal nodes Superficial perineal region (e.g. superficial perineal pouch) Labia majora + minora Scrotal & penile skin + associated connective tissue Distal part of anal canal (inferior to pectinate line): remember superior to pectinate line = internal iliac nodes Uterine body via round ligament to labia Lower limb + lower abdominal wall Deep inguinal nodes Lymph from superficial nodes Corpora cavernosa of penis and clitoris, glans penis Superficial and deep inguinal nodes drain into the common iliac nodes

Answer 252

Sympathetic innervation: From T10-L2 lumbar splanchnic nerves via hypogastric plexi From L1-L2/3 sacral splanchnic nerves via sympathetic chain and inferior hypogastric plexus Parasympathetic innervation: From S2 – S4 pelvic splanchnic nerves via inferior hypogastric plexus Visceral afferent fibres above the pain line travel through sympathetic nerves to T10 – L2 spinal cord segments Visceral afferent fibres below the pelvic pain line travel through parasympathetic nerve fibres (pelvic splanchnic nerves) to S2 – S4 spinal cord segments Somatic innervation to pelvic floor and perineum Pudendal nerve (anterior rami of S2 – S4 spinal nerves)

Answer 253

Anterior surface: ilioinguinal nerve (L1) Anterolateral surface: genital branch of genitofemoral nerve (L1,L2) Posterior surface: posterior cutaneous nerve of the thigh (S1-S3), pudendal nerve (S2-S4)

Answer 254

Erection is a vascular event stimulated by parasympathetic nerve fibres Parasympathetic nerve fibres from S2-S4 travel through the pelvic splanchnic nerves Pelvic splanchnic -> inf. hypogastric plexi -> prostatic plexus -> cavernous nerves

Answer 255

Stimulation of parasympathetic nerve fibres leads to vasodilation of the cavernous arteries  helicine arteries fill the sinusoidal spaces in the corpora cavernosa with blood In the flaccid penis, anastomoses between the cavernous arteries and deep dorsal veins of the penis allow blood to bypass the corpora cavernosa In the erect penis, engorgement of the corpora cavernosa compresses the deep dorsal vein against the deep penile fascia  aids in the maintenance of erection Bulbospongiosus and ischiocavernosus muscles also compress venous plexus helping to maintain erection

Answer 256

Ejaculation is achieved through activation of the sympathetic system Sympathetic fibres cause contraction of smooth muscle in the epididymis, ductus deferens, seminal vesicles, and prostate  sperm moves towards the prostatic urethra The internal urethral sphincter contracts to prevent retrograde ejaculation into the bladder Contraction of smooth muscle in the urethra, and bulbospongiosus muscle aid in ejaculation

Answer 257

Ischiocavernosus and bulbospongiosus muscles cover the roots of the external genitalia Innervated by the pudendal nerve (ant. rami of S2-S4 spinal nerves) Contraction helps maintain erection of the clitoris and penis Bulbospongiosus supports the perineal body In males, contraction of bulbospongiosus aids in ejaculation and urination In females, contraction of bulbospongiosus empties the greater vestibular glands  lubrication of the vagina

Answer 258

Intermediate mesoderm forms the gonadal (genital) ridges

Answer 259

Three sets of kidneys develop sequentially in the embryo: Pronephros: transient non-functional “kidney” that develops from intermediate mesoderm in week 4 and is quickly lost Mesonephros: transient functional kidney (also from intermediate mesoderm) that forms in week 4 Forms nephrons which degenerate by week 8 The mesonephric ducts will form the male reproductive tract Metanephros: the permanent kidneys develop from the caudal part of the gonadal ridges (metanephric mesoderm) and the ureteric buds (offshoots of the mesonephric ducts)

Answer 260

Metanephros: the permanent kidneys develop from the caudal part of the gonadal ridges (metanephric mesoderm) and the ureteric buds (offshoots of the mesonephric ducts) Ureteric bud forms the ureter, renal pelvis, major and minor calyces and collecting ducts Kidneys form in the pelvis from week 5 onwards and ascends during development to their adult anatomical location at T12-L3 The gonads develop on the posterior abdominal wall and descend during development to their proper anatomical location in the pelvis or scrotum. Kidneys are functional by week 12 – fetus swallows amniotic fluid which is then excreted as urine During fetal life the placenta is more important for excreting waste products

Answer 261

Fusion of inferior poles of both kidneys in the midline: single large U-shaped kidney Fusion site is below the inferior mesenteric artery – vessel limits kidney ascent Renal tissue crossing midline is around L3 vertebral level 2:1 male:female incidence, may be undetected until later in life More common in genetic conditions such as Down syndrome and Turner syndrome Increased risk of urinary reflux, urinary obstruction, UTIs, kidney stones

Answer 262

Metanephros fails to develop properly Other kidney undergoes hypertrophy to compensate Bilateral renal agenesis is incompatible with life

Answer 263

One kidney fails to fully ascend in the abdomen ‘Pelvic kidney’ if it remains in the pelvic region Similar risks as with horseshoe kidney

Answer 264

Caused by abnormal branching of the ureteric bud Bifid ureter = partial division with same entry point into the bladder Double ureter = complete division with separate entry points into the bladder Increased risk of urinary reflux, infections

Answer 265

During weeks 4 – 7 the cloaca is divided by a layer of mesoderm known as the urorectal septum to form the urogenital sinus and anal canal The urogenital sinus (ventral part of the cloaca) will form the bladder and urethra Endoderm forms the epithelial lining of the bladder and urethra The bladder is initially continuous with the allantois The allantois is initially hollow (allantoic duct) but fills in with fibrous connective tissue to become the urachus, which in adults is the median umbilical ligament The tip of the urorectal septum forms the perineal body

Answer 266

Allantois fails to fill in with connective tissue to become the urachus and median umbilical ligament, persists as a hollow tube connected to the bladder Urine can leak through umbilicus Risk of infection

Answer 267

Part of allantois persists as fluid-filled cyst Often no urinary signs/symptoms, may be palpable or cause abdominal/pelvic pain

Answer 268

Distal/upper part of allantois fails to close Persists as a blind ending that is open at the umbilicus but doesn’t communicate with the bladder May become infected

Answer 269

Primordial germ cells move from the yolk sac and allantois into the gonadal ridges by week 6 Migrate along the dorsal mesentery of the hindgut to reach the gonadal ridges No migration = gonadal agenesis Surface epithelium of each gonadal ridge proliferates and penetrates the underlying mesenchyme to form primitive sex cords Male and female gonads cannot be distinguished at this stage: indifferent gonad Outer cortex Inner medulla Fate of both regions depends on the production of testis-determining factor (TDF) Presence of SRY gene (sex-determining region of Y chromosome) important for initiating production of TDF No Y chromosome = no TDF produced, so female development begins

Answer 270

Two sets of genital ducts form: Mesonephric (Wolffian) ducts = male reproductive tract Paramesonephric (Müllerian) ducts = female reproductive tract

Answer 271

Absence of Y chromosome and TDF causes primitive sex cords in the future ovarian medulla (medullary cords) to break up into cell clusters and eventually disappear Surface epithelium proliferates to form cortical cords which will produce oogonia surrounded by follicular cells Oogonia undergo mitosis to form primary oocytes Primordial follicle = primary oocyte + follicular cells

Answer 272

Presence of Y chromosome and TDF causes primitive sex cords to continue to proliferate in the testicular medulla and form testis cords (testicular cords) Thick tunica albuginea layer forms between surface epithelium and testis cords Testis cords near testicular hilum break up to form tubules of the rete testis Interstitial cells (of Leydig) form by week 8: testosterone production By fourth month the testis cords are composed of spermatogonia and sustentacular cells (of Sertoli) Testis cords are solid until they form a lumen at puberty: seminiferous tubules

Answer 273

Testosterone from interstitial cells (of Leydig) encourages the mesonephric ducts to elongate and form the epididymis, ductus deferens and seminal vesicles Prostate forms as a bud from the urethra Anti-mullerian hormone from sustentacular cells (of Sertoli) stops the paramesonephric ducts from developing further, causing them to regress Appendix testis and prostatic utricle are small remnants of the paramesonephric ducts

Answer 274

Mesonephric ducts not involved – these ducts regress in the absence of testosterone and anti-mullerian hormone Each paramesonephric duct opens at the cranial end into the developing peritoneal cavity – future site of fimbriae of the uterine tubes Caudal ends of each paramesonephric duct fuse in the midline to form the uterovaginal canal Will form uterus and proximal/upper vagina Broad ligaments formed too as peritoneum is pulled towards midline Distal/lower vagina forms from urogenital sinus (vaginal plate)

Answer 275

All caused by abnormal paramesonephric duct development

Answer 276

Ovaries descend into the pelvic cavity Connected to the inguinal region by the gubernaculum Ovaries prevented from descending further by the formation of the broad ligament Gubernaculum will form the ovarian ligament and round ligament of the uterus

Answer 277

Testes descend much further to enter the scrotum via the inguinal canal Connected to future site of scrotum by the gubernaculum No paramesonephric ducts = no broad ligament, so gonad can descend further Testes usually enter the scrotum by 33 weeks Inguinal canal formed by the processus vaginalis (outpouching of peritoneum) Grows ahead of the testis – helps provide space for testis to enter the scrotum Processus vaginalis pushes through the three developing layers of the anterior abdominal wall (aponeuroses of external oblique, internal oblique and transversus abdominis) Processus vaginalis usually closes before birth except for the tunica vaginalis anterior to the testis Factors controlling testicular descent Enlongation of the fetal torso Increase in intra-abdominal pressure as GI tract organs form Regression of the gubernaculum

Answer 278

One or both testes have not fully descended into the scrotum May be smaller and firmer than a typical testis Cryptoorchidism can resolve itself before first birthday Orchiopexy (surgical repositioning of affected testis) pre-puberty to ensure proper development of the seminiferous tubules and spermatozoa Untreated bilateral cryptorchid testes = azoospermia Untreated unilateral cryptorchid testis = oligospermia Increased risk of testicular torsion, inguinal hernias Abdominal cryptorchidism has increased risk of testicular germ cell tumours if untreated

Answer 279

Cloacal folds around the cloacal membrane will form the genital tubercle superiorly and two urethral folds inferiorly Genital swellings develop beside the urethral folds Will go on to form either the labia majora or scrotum

Answer 280

Genital tubercle forms the clitoris under the influence of oestrogen Urethral folds do not fuse – form the labia minora Allows the vestibule (of vagina/vulva) to form Urethra opens into vestibule Genital swellings enlarge and become the labia majora

Answer 281

Genital tubercle elongates under the influence of dihydrotestosterone to become the phallus The urethral folds fuse together by the end of the third month and seal off the urethral plate (from endoderm, forms lining of urethra) to form the penile urethra External urethral meatus and distal penile urethra of the glans are formed by ectodermal tissue Prepuce (foreskin) starts to separate away from the glans Scrotal swellings enlarge and fuse together to form the scrotum and scrotal septum Line of fusion persists as a visible raphe (‘seam’) on the penis, scrotum and perineum

Answer 282

Hypospadias: abnormal opening of the urethra along the ventral aspect of the penis caused by incomplete fusion of urethral folds First degree hypospadias: urethra opens onto glans penis Second degree hypospadias: urethra opens on ventral aspect of penile shaft/body Third degree hypospadias: urethra opens on perineum or scrotum Can affect development of glans and foreskin (C) May be associated with chordee (congenital penile curvature)

Answer 283

: urethral opening is on the dorsal aspect of the penis More associated with exstrophy of the bladder - abnormal closure of anterior abdominal wall with open bladder (D)

Answer 284

Hydrocele: excessive fluid build-up between the visceral and parietal layers of the tunica vaginalis, or within a cyst along the course of the processus vaginalis Clear serous fluid May cause significant scrotal swelling Ipsilateral testis can be more difficult to palpate due to the swelling Haematocele: blood in tunica vaginalis e.g. due to scrotal trauma

Answer 285

Spermatocele (spermatic cyst): fluid-filled cyst formed from a diverticulum on the head of the epididymis Milky fluid containing spermatozoa Cyst is superior to the ipsilateral testis Testis can still be palpated Epididymal cysts are fluid-filled cysts elsewhere along the epididymis

Answer 286

Pampiniform plexus of veins in spermatic cord becomes varicose and tortuous May be caused by defective venous valves Palpable enlargement superior to the ipsilateral testis – ‘bundle of worms’ More common on left side and more visible when standing, disappears when lying flat

Answer 287

Initiated by erotic stimuli (physical, visual, chemical, proceptive behaviour) Penis stiffens and increases in length and diameter - tumescent Urethral opening widens Scrotal skin becomes congested and thickened (scrotal diameter reduced) Testes elevated by contraction of cremaster muscle Nipples become erect (60%), reddened skin ‘sex flush’ (50-60%) Increased HR, breathing depth & rate, and BP

Answer 288

Occurs due to continued presence of erotic stimuli Slight increase in size of glans, deepened colour Urethral bulb enlarges (x3) Preorgasmic emission from Cowper’s gland Testes more elevated, rotate and lie closer to groin Prostate gland enlarges Further increase in HR, breathing depth & rate, and BP Redness spreads & increases in intensity (if present)

Answer 289

Loss of voluntary control of muscles Testes at maximum elevation HR(180 bpm), respiratory rate (41 breaths/min), BP (200/110) all peak Redness peaks in intensity and distribution (if present) Smooth muscle contractions expel ejaculatory fluid into urethral bulb (emission) Rhythmic contractions of surrounding musculature result in forceful expulsion Contractions approx. 0.8s apart – 1st 3-4 are the most forceful and expel majority of fluid

Answer 290

Immediately after ejaculation Erotic stimuli are not effective at initiating/maintaining an erection Refractory period tends to increase with age

Answer 291

Occurs during and after the refractory period (if no effective erotic stimulus is present) Arousal mechanisms return to a resting state 50% of penis size is lost rapidly Muscle tension & redness disappear HR, respiratory rate and BP will decrease within 5 mins Final reduction in penis size, relaxation of scrotum, decent of testes and loss of nipple erection take longer Entire resolution phase – up to 2hr Can be lengthened (physical contact) or shortened (urination)

Answer 292

Dilation of arteries and arterioles leading to increased blood flow Trapping of incoming blood by expanding sinusoids Compression of subtunical venular plexuses between the tunica albuginea and peripheral sinusoids leading to reduces venous outflow Stretching of the tunica which occludes veins between the inner circular and outer longitudinal layers leading to further decreases venous outflow Increased intracavernous pressure raises penis to the erect state Further pressure increase with contraction of ischiocavernosus muscles

Answer 293

Forcible ejection of seminal fluid from urethral meatus that commonly accompanies sexual climax and orgasm Process divided into emission and expulsion Minor expulsion from the Cowper’s gland (bulbourethral gland) can occur before main expulsion Contains spermatozoa at a similar concentration – pregnancy despite coitus interruptus

Answer 294

Closure of bladder neck – sympathetic innervation at the base of the bladder Prostatic secretions (acid phosphatase, citric acid, zinc) mix with spermatozoa from the vas deferens – ejected into prostatic urethra Seminal vesicle fluid (fructose) alkalinises the final ejaculatory product Minor contributions by Cowper’s glands and periurethral glands Total contributuion: Prostate – 10% Vas Deferens – 10% Seminal Vesicle – 75-80% Discharge of ejaculatory fluid from the urethra Relaxation of external urethral sphincter (bladder neck still closed) Rhythmic contractions of prostate, bulbospongiosus & ischiocavernosus muscles, pelvic muscles (levator ani & transverse perineal) Afferent signal is not clear Efferent signal from pudendal nerve (somatic)

Answer 295

Retroperitoneal organ, encircling the neck of bladder and urethra. Prostate weighs 20 grams in normal adult Devoid of a distinct capsule Four distinct zones including: - a central zone (CZ), - a peripheral zone (PZ). Place for most carcinoma - a transitional zone (TZ), Place for hyperplasia - a periurethral zone.

Answer 296

Histologically the prostate is composed of glands lined by two layers of cells. A basal layer of low cuboidal epithelium covered by a layer of columnar secretory cells. In many areas there are small papillary infoldings of the epithelium. These glands are separated by abundant fibromuscular stroma.

Answer 297

Accessory sex gland Main function is to secrete prostate fluid. Notable contents: PSA, Prostaglandins, Fructose, Zinc, Citrate The muscles of the prostate gland also help propel this seminal fluid into the urethra during ejaculation PSA: liquefying semen that has thickened after ejaculation. This thinning action allows sperm to swim more freely

Answer 298

Acute (suppurative prostatitis) E.coli, rarely Staph or N. gonorrhoeae Chronic: Chronic non-specific prostatitis or diagnosed by increased leucocytes in prostatic secretions but no bacteria found: Chronic abacterial prostatitis. Granulomatous: e.g. disseminated TB, allergic(eosinophilic) SYMPTOMS: Dysuria, frequency, lower back pain, pelvic pain DRE: enlarged tender prostate

Answer 299

Proliferation of both stromal and epithelial elements (glands). Incidence: Old age: 20% in men over age 40,up to 70% by age 60, and 90% by age 70. Ethnicity: Common in black > White> Asian. Related to the action of androgen.

Answer 300

Dihydrotestesterone (DHT ) is the ultimate mediator for prostatic growth. It is formed in the prostate from the conversion of testosterone by the enzyme type 2 5α-reductase, located almost entirely in stromal cells; Epithelial cells of the prostate do not contain type 2 5α reductase. Type 1 5α-reductase is not detected in the prostate. However, this enzyme may produce DHT from testosterone in liver and skin. Circulating DHT may act in the prostate by an endocrine mechanism. Enlargement occurs almost in the Transitional zone (TZ).

Answer 301

Enlargement occurs almost in the Transitional zone (TZ).

Answer 302

Voiding symptoms (Obstructive): weak or intermittent urinary flow, straining, hesitancy, terminal dribbling and incomplete emptying. Storage symptoms (Irritative): urgency, frequency, incontinence and nocturia. Complications: Urinary tract infection, retention, obstructive uropathy.

Answer 303

Obstructive Uropathy Bladder hypertrophy Trabeculation Diverticula formation Hydroureter – bilateral Hydronephrosis Lithiasis / stone. Secondary infection.

Answer 304

) α1-antagonists e.g Tamsulosin which decrease prostate smooth muscle tone (prostate and bladder neck). Adverse effects: dizziness, postural hypotension and dry mouth. 2) 5-α-reductase inhibitors e.g Finasteride - block the conversion of testosterone to DHT. - causes reduction in prostate volume. - takes about 6 months to improve the condition. - Adverse effects: erectile dysfunction, reduced libido, ejaculation problems and gynaecomastia. if there is a mixture of storage symptoms and voiding symptoms that persist after treatment with an alpha-blocker alone, then an antimuscarinic (anticholinergic) drug such as tolterodine or darifenacin may be tried Surgical: Transurethral resection of the prostate (TURP).

Answer 305

Partial removal by resectoscope. Complications: Haemorrhage, Infection, Granulomatous prostatitis and Retrograde ejaculation. TURP syndrome: - excessive irrigation used during the operation for better visualisation >> irrigation fluid enters the systemic circulation through the prostatic veins>> Hyponatremia (less Na). - Clinical picture: confusion, bradycardia, nausea and vomiting. - treatment: fluid restriction.

Answer 306

Testosterone is the key for BPH development. Presents with lower urinary tract symptoms (LUTS) which can be storage symptoms (frequency, urgency, nocturia, and incontinence) and voiding symptoms (weak stream, dribbling, dysuria, straining). Physical examination may demonstrate prostate volume ≥30 g, smooth surface. Treated with an alpha 1-blocker, 5-alpha-reductase inhibitors, combination therapy. Common complications are disease progression and urinary retention, which may require invasive therapy. Failure of medical management or renal complications are indications for surgical intervention (TURP)

Answer 307

The most common form is adenocarcinoma (glandular prostate cancer). They form in the glandular epithelial cells that line the insides of the organs and secrete mucus, digestive juices or other fluids. Two main subtypes of adenocarcinoma of the prostate are: 1. Acinar adenocarcinoma (conventional adenocarcinoma): This cancer accounts for virtually all prostatic adenocarcinomas. Acini cells line the prostate’s fluid-secreting glands. The cancer starts growing in the back (periphery) of the prostate near the rectum and may be felt during a doctor’s digital rectal exam. The disease increases PSA levels. 2. Prostatic ductal adenocarcinoma (PDA): Prostatic ductal adenocarcinoma (PDA): This cancer is a rarer but more aggressive form of adenocarcinoma. It develops in the cells lining the tubes and ducts of the prostate gland. When it occurs, it frequently develops along with acinar adenocarcinoma. This cancer type doesn’t necessarily increase PSA levels, making it harder to detect. Microscopic Examination: - Prostate glands are typically smaller than benign glands. Lined by a single uniform layer of cuboidal or low columnar epithelium. The outer basal cell layer typical of benign glands is absent. Cancer glands are more crowded, and characteristically lack branching and papillary infolding.

Answer 308

Early stages usually asymptomatic: Most cases detected by serum PSA screening Palpable nodule or firmness on DRE Advanced stages: Urinary retention/renal failure Bone pain Anaemia Weight loss, fatigue Spinal cord compression

Answer 309

Early stage Cancer Prostatectomy Radiotherapy Radioactive Seeds (Brachytherapy) Advanced Prostate Cancer Androgen Deprivation Antiandrogens Supportive therapies Analgesics Steroids Vitamin D/Calcium Chemotherapy

Answer 310

Prostatitis - Dysuria, - Frequency, - Lower back pain, - Pelvic pain and DRE enlarged tender prostate BPH Lower UT obstruction Hesitancy Interruption of flow DRE : Enlarged smooth prostate Prostate Cancer - Back pain DRE: Craggy prostate OR Similar to BPH

Answer 311

Renal hilum at the medial surface Renal vein anterior to the renal artery Renal artery anterior to the renal pelvis

Answer 312

Posteriorly the kidneys are associated with the diaphragm and from medial to lateral with: Psoas major muscle Quadratus lumborum muscle Transversus abdominis muscle

Answer 313

Costodiaphragmatic recess of pleura extends over the superior pole of the kidneys  must be avoided e.g. in kidney biopsy

Answer 314

Located between the T12 and L3 vertebral levels Deep to 11th and 12th ribs The right kidney usually lies lower than the left Costodiaphragmatic recess of pleura extends over the superior pole of the kidneys  must be avoided e.g. in kidney biopsy

Answer 315

The right kidney associated with the right suprarenal gland, the liver, 2nd part of duodenum, ascending colon, right colic flexure, small intestine The left kidney is associated with the left suprarenal gland, the stomach, the spleen, the pancreas, left colic flexure, descending colon, and jejunum

Answer 316

Renal cortex: outer layer, contains parts of nephrons and collecting tubules Renal medulla: divided into renal pyramids Minor calyces: receive urine from collecting ducts of renal pyramids Major calyces: formed by the unison of minor calyces Renal pelvis: formed by the unison of 2-3 major calyces

Answer 317

Kidneys supplied by the left and right renal arteries Renal arteries are direct branches from the abdominal aorta at L1/L2 vertebral level Right renal artery passes posterior to the inferior vena cava May have accessory renal arteries Drain into the inferior vena cava via renal veins

Answer 318

Renal -> segmental -> interlobar -> arcuate ->interlobular -> afferent -> glomerulus -> efferent -> vasa recta/peritubular -> interlobular veins etc

Answer 319

Sympathetic innervation From T11-L2 spinal cord segments Abdominopelvic splanchnic nerves via renal nerve plexus Sympathetic input causes vasoconstriction and renin release Visceral afferent innervation Afferent nerve fibres travel to T11-L2 spinal cord segments with sympathetic nerves Referred pain to lower abdomen and back

Answer 320

The ureters are muscular tubes, 25-30cm long Retroperitoneal, descend on psoas major muscle Transport urine from the kidneys to the bladder by peristaltic contractions At the pelvic inlet, they cross the common iliac or external iliac artery

Answer 321

3 sites of constriction: Uretopelvic junction, pelvic inlet, entrance to bladder

Answer 322

Blood supply Renal arteries -> abdominal part of ureters Branches from the gonadal arteries and abdominal aorta Branches from the common iliac artery Branches from the internal iliac artery – superior vesical, uterine, vaginal/inferior vesical Venous drainage follows the arterial supply

Answer 323

Autonomic and visceral afferent nerve fibres from renal, aortic, superior and inferior hypogastric plexi Visceral afferent fibres transmitted to T11-L2/L3 spinal cord segments Pain referred to lower abdomen, perineum, medial thigh  “loin to groin” presentation Ureteric colic pain with waves of peristalsis

Answer 324

Holds ~300-500 mL of urine Has a smooth area between the openings of the ureters and the internal urethral orifice  trigone of the bladder Smooth muscle fibres in the bladder wall  detrusor muscle Rugae allow bladder to expand

Answer 325

Arterial supply Internal iliac arteries via superior vesical artery, inferior vesical/vaginal arteries Venous drainage Internal iliac veins via vesical/ prostatic venous plexus

Answer 326

Bladder Extends over the pubic symphysis when full Suprapubic catheterisation indicated when transurethral catheterisation is not possible or when surgical access to the urethra is required

Answer 327

Kidneys Lateral aortic (lumbar) lymph nodes Ureters Superior part -> lateral aortic nodes Middle part -> common iliac nodes Inferior part -> external and internal iliac nodes Bladder External and internal iliac nodes

Answer 328

Female External urethral sphincter only (assisted by sphincter urethrovaginalis and compressor urethrae muscles) Located in the deep perineal pouch Somatic innervation through the pudendal nerve (S2-S4) Male Internal urethral sphincter Located in the pre-prostatic urethra Smooth muscle Continuous with detrusor muscle External urethral sphincter In the deep perineal pouch Skeletal muscle

Answer 329

Bladder at rest Sympathetic input from T10 – L2 spinal cord segments via inferior hypogastric plexus Detrusor muscle is relaxed Rugae allow bladder to expand Internal urethral sphincter is contracted External urethral sphincter is contracted (pudendal nerve) Micturition Parasympathetic stimulation from S2 - S4 spinal cord segments via pelvic splanchnic nerves Stretch receptors are stimulated Contraction of detrusor muscle and relaxation of internal urethral sphincter External urethral sphincter relaxes (pudendal nerve) Higher CNS control can supress micturition reflex

Answer 330

"Overactive bladder” Most common cause of incontinence in elderly people Involuntary bladder contraction caused by detrusor muscle overactivity Involuntary urine leakage accompanied by or immediately preceded by sensation of urgency to urinate Usually idiopathic but may be neurogenic e.g. due to stroke, multiple sclerosis

Answer 331

Involuntary loss of urine after increase in intraabdominal pressure e.g. coughing, sneezing More common in females Associated with weakening of pelvic floor support structures Pubovesical ligaments Levator ani muscles Pubovesical fascia May be associate with urethral sphincter damage

Answer 332

Involuntary leakage of urine from overfull bladder due to chronic urine retention. May be caused by urethral obstruction e.g from benign prostatic hyperplasia, pelvic organ prolapse, urethral stricture May be due to weakened detrusor muscle

Answer 333

Regulation Regulates body water balance, osmolarity and volumes Regulates quantity and concentration of electrolytes Regulates acid-base balance Excretion Excretes end products of metabolism e.g urea (amino acids), uric acid (nucleic acids), creatinine (muscle creatinine) and bilirubin (haemoglobin) Excretes many drugs and foreign or toxic compounds Degrades several hormones (e.g. insulin, parathyroid hormones) Produces/secretes Produces and secretes renin, calcitriol, and erythropoietin Contributes to glucose synthesis (gluconeogenesis) in fasting states Synthesis of ammonia (acid-base homeostasis) Synthesis of substances that affect renal blood flow and Na+ excretion e.g. prostaglandins and proteolytic enzymes that produce kinins

Answer 334

Leads to failure of renal excretion and retention of nitrogenous waste products of metabolism including creatinine and urea and reduced regulatory functions

Answer 335

Waste product accumulation - uraemia, appetite loss, lethargy, nausea, vomiting, weightloss, itching, muscle cramps etc Inability to excrete water (fluid overload) – breathlessness, orthopnoea, oliguria, peripheral oedema

Answer 336

Consequence Cause Hypertension Due to disruption of renin in response to impaired perfusion Cardiovascular disease Ischaemic heart disease is common and often a combination of arteriolosclerosis and atherosclerosis Anaemia Destruction or renal tissue results in erythropoietin and iron deficiency Disorders of Ca2+ metabolism Impaired calcitriol production results in Vit D deficiency and can be associated with secondary hyperparathyroidism Hypoproteinaemia Persistent, chronic urinary loss and can lead to impaired protein binding with adverse reactions from therapeutic agents, wasting, malnutrition Metabolic complications Defective excretion of urate results in gout and of insulin results in hypoglycaemia in insulin-dependent diabetics Neurological complications Severe, persistent uraemia depresses cerebral function and may cause convulsions

Answer 337

a) Blood capillaries Glomerulus Peritubular (cortical) or vasa recta (juxtamedullary) b) Single cell hollow tubules Divided into 5 segments Unique histology & transporters

Answer 338

Cortical 80% Peritubular capillaries Role: filtration Juxtamedullary nephrons 20% Long loops of Henle, vasa rectae Role: concentrating and diluting urine

Answer 339

PCT - Majority of reabsorption Loop of Henle - Thick & thin portions - Different permeabilities - Sets up an osmotic gradient DCT - Fine tuning - Hormonally regulated CD - Hormonally regulated action (e.g anti-diuretic hormone, aldosterone, atrial natriuretic peptide). - Intercalated & principal cells

Answer 340

PCT - Simple cuboidal with microvilli and lots of mitochondria Descending loop - simple squamous Ascending loop - simple columnar DCT - Simple cuboidal with lots of mitochondria CD - Simple cuboidal with intercalated (H+ secretion) and principle cells (bicarb secretion)

Answer 341

PCT and DCT - due to lots of mitochondria

Answer 342

Specialisation where the DCT loops between the afferent and efferent arteriole By monitoring the NaCl as it enters the DCT, the macula densa can activate the renin-angiotensin-aldosterone system, if needed, to regulate renal blood flow, blood pressure and the fluid balance

Answer 343

Macula densa Densely crowded DCT epithelial cells monitor [NaCl ] in the DCT fluid. Paracrine factors release to alter arteriole resistance Juxtaglomerular cells Modified smooth muscle cells in the afferent arterioles, richly sympathetically innervated and contain renin granules Extraglomerular mesangial cells (lacis) Transmit macula sensa signals to the granular cells

Answer 344

Efferent sympathetic fibers run adjacent to the major branches of the renal artery and its branches Constricts vascular smooth muscle to reduce renal blood flow Innervates tubular cells and the granular cells producing renin Increases transporter activity to increase Na+ and water reabsorption Increases renin release Contributes to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease Afferent sensory nerve fibers in the renal pelvic wall are stimulated by stretch (and chemicals). Renorenal reflex (inhibitory) – e.g. increased sensory activation reduces the sympathetic nerve activity. Renal efferent nerve activity can affect the ipsilateral/contralateral side to facilitate regulation of sodium and water balance and blood pressure.

Answer 345

Filtration fraction (FF) is the fraction of renal plasma flow that is filtered per minute (min). FF = GFR/ RPF

Answer 346

Capillary endothelial fenestrae (50-100nm) Basement membrane Porous, negative charge due to proteoglycans Epithelial podocytes & pedicels form filtration slits (40nm) Porous, negative

Answer 347

Endocytosis acts as a salvage system

Answer 348

Kf is a product of the hydraulic conductivity and the glomerular capillary surface area =GFR/net filtration pressure

Answer 349

Glomerular hydrostatic pressure - Bowman's capsule pressure - Glomerular colloid pressure

Answer 350

BC hydrostatic pressure opposes GFR It opposes the net filtration so affects the fluid movement into tubules Increased tubular pressure reduces GFR Blockade in the urinary tract urinary stones, ureteral obstruction, prostate enlargement Increased tubular fluid pressure needing an increased pressure head e.g. lack of water reabsorption or effect diuretic agents

Answer 351

Glomerular capillary osmotic pressure opposes GFR Increasing arterial plasma proteins decreases GFR Lowering arterial plasma proteins e.g. dilution with iv. isotonic saline increases GFR. Increasing FF (i.e. GFR/RPF) concentrates plasma proteins so opposing osmotic pressure Increasing RBF causes a lower fraction of plasma to initially filtered causing a slower rise in the capillary osmotic pressure so increases GFR i.e. greater blood flows increase the GFR (and vice versa)

Answer 352

The afferent arteriolar resistance Constriction increases resistance, lowers capillary hydrostatic pressure and GFR Dilation has the opposite effect The efferent arteriolar resistance: Mild constriction increases GFR Severe constriction reduces GFR due to opposing plasma protein concentration rising

Answer 353

Decreased Kf - Renal disease, diabetes mellitus, hypertension, aging Increased BC hydrostatic pressure - Urinary tract obstruction e.g. kidney stones Increased Glomerular capillary osmotic/colloidal pressure - Low renal blood flow, raised plasma proteins Decreased Glomerular capillary hydrostatic pressure - Low arterial pressure (though effect is small as it is autoregulated) Decreased Efferent arteriolar resistance - Low angiotension II (e.g. drugs that inhibit angiotensin II formation) Increased Afferent arteriolar resistance - Raised sympathetic activity or vasoconstrictor hormones (e.g. Norephinephrine or endothelin)

Answer 354

Strong systematic sympathetic innervation constricts renal arterioles to reduce RBF and GFR whilst moderate or mild stimulation has little effect. e.g. from baroreceptor reflex responses Mild increases from renal sympathetic activity mediates renin release and increase tubular reabsorption to decrease salt and water excretion.

Answer 355

When BP rises or drops, blood vessels upstream to the glomerulus constrict or dilate to maintain glomerular blood flow and capillary pressure Increases in vascular pressure stretches blood vessel walls Stretch-activated cation channels opens voltage dependent Ca2+ channels and intracellular Ca2+ rises, causing contraction (vice versa)

Answer 356

Involves the Juxtaglomerular feedback apparatus Links changes in NaCl concentration at the macula densa to arteriolar resistance (afferent and efferent feedback) and GFR e.g. GFR Decreased Lower NaCl detected by macula densa cells Renin release -> efferent constriction ATP -> Adenosine -> Afferent vasodilation

Answer 357

RBF and GFR increased after meals and also due to kidney growth Effect is due to amino acid and Na+ reabsorption in PCT being linked TGF effect: Macula densa senses reduced Na+ in DCT causing afferent vasodilation to increase RBF and GFR and increase waste products of protein excretion (urea)

Answer 358

Glucose reabsorption is linked to Na+ reabsorption in PCT TGF effect: Macula densa senses reduced Na+ in DCT causing afferent vasodilation to increase RBF and GFR

Answer 359

Less Na+ reabsorption, more delivered to DCT and more excretion and excess volume depletion

Answer 360

Decrease in urine production (oliguria), can be total (anuria) Uremia, nitrogen retention, increased serum K, metabolic acidosis Removal of damaging stimulus can restore total kidney function. Measured by reestablishment of urinary flow which may be excessive to begin with (polyuria)

Answer 361

Infection of renal parenchyma and renal pelvis – often from UTI ▪ Can be caused by gram –ve bacteria Escherichia coli ascending from bladder ▪ or from blood (Staphylococcus aureus). Acute: loin area pain on 1 or both sides, chills and fever, dysuria, frequency, urgency, N&V, antimicrobials ▪ Chronic: scarring of calyces and pelvis, most often caused by vesicourethral reflux/recurrent acute pyelonephritis/UTI

Answer 362

Affect tubules (PCT and DCT) and interstitial tissues ▪ Caused by: ▪ Infection ▪ Ischaemia ▪ Toxic damage ▪ Acute interstitial nephritis (AIN) associated with antibiotics and NSAIDs, which act as haptens, inducing a hypersensitivity reaction ▪ Ischaemia and toxic damage can lead to acute tubular necrosis (ATN)

Answer 363

▪ Often known as ATN but this is NOT A NECROTIC PROCESS ▪ Shed dead cells block the tubules – oliguric phase (50-400ml/day - risk of acute renal failure) * Recovery often begins with polyuria – polyuric phase (up to 3L/day). Due to phagocytosis of necrotic cells, tubules are opened up again – but lining cells are not mature enough to be fully functional. Ensure replacement of fluid and electrolytes – risk of fluidelectrolyte imbalance and infection * Recovery phase- return to homeostasis as ductal epithelial cells mature Caused by ischaemic (vasoconstriction) or toxic damage to tubular epithelium ▪ Poorly perfused glomerulus causes death of epithelium of DCT and PCT (these cells have a high metabolic demand)

Answer 364

▪ ‘inflammation of glomeruli’ 4 structures in glomerulus that can be damaged: ▪ Capillary endothelium ▪ Glomerular basement membrane ▪ Mesangial cells ▪ Podocytes Often involves the immune system

Answer 365

Urinary stasis (risk of infection, dilation of ducts) ▪ Dilation of pelvis and calyx due to urine retention: hydronephrosis ▪ Dilation of the ureter - hydroureter ▪ Unilateral is clinically silent for a long time due to compensation from the other kidney ▪ Bilateral causes oliguria/anuria

Answer 366

Diabetic nephropathy

Answer 367

a progressive loss of renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite

Answer 368

▪ Arteriolosclerosis of renal arterioles causes ischaemia in the nephrons

Answer 369

Heart failure - Na/H2O imbalance Hyperkalaemia Uraemia - systemic manifestations Erythropoietin - anaemia hypocalcaemia - vit D/Phosphate

Answer 370

If Renal CL < 125 ml/min, the drug is either not filtered or it is filtered then reabsorbed If Renal CL > 125 ml/min then the drug is secreted

Answer 371

Increased gastric pH oedema of GI tract Nausea, vomiting diarrhoea Delayed gastric emptying Decreased absorption, decreased bioavailability -> Decreased Cmax, Increased Tmax Decreased first pass - > Increased Cp

Answer 372

Hydration status esp for water soluble drugs with small Vd e.g. aminoglycosides Protein binding Hypoalbuminaemia esp for acidic drugs Uraemia Albumin structure altered Tissue binding E.g. digoxin is normally bound within tissues In CKD, there is reduced binding in the tissues - reduced Vd, increasd Cp What effect do these processes have on the apparent volume of distribution? Increased [free drug]  increased Vd

Answer 373

effect on expression and activity of some cytochrome P450 isoenzymes is controversial. changes in metabolic clearances noted in CKD may be due to changes in expression or function of drug transporters e.g. on the hepatocyte cell membrane

Answer 374

Glomerular filtration Reduced Molecular weight and protein binding Active tubular secretion Reduced saturable Tubular reabsorption Altered by pH of urine Generally reduced

Answer 375

Dose adjustment - most concerned when.. CrCl < 50mL/minute Drug > 50% renally excreted unchanged Drug with narrow therapeutic range Age

Answer 376

Prostaglandins cause afferent vasodilation and so increase GFR If prostaglandin PGE2/I2 production blocked by NSAIDs, there is no (or not enough) vasodilation and insufficient blood flow through arterioles. + Effect on Na+/H2O renal homeostasis

Answer 377

Normally, Angiotensin is a Potent vasoconstrictor - Predominant action on efferent arteriole to maintain GFR ACEIs can induce acute renal insufficiency in patients with bilateral renal artery stenosis, stenosis of the artery to a single remaining kidney, heart failure, or volume depletion owing to diarrhea or diuretics

Answer 378

Normal: Pre-renal AKI Post-renal AKI Renovascular Blood and protein: Nephritic syndrome Glomerulonephritis Vasculitis Acute tubular necrosis Protein only: Glomerulopathy Nephrotic Syndrome Blood only: Urological Rhabdomyolysis ATN Glomerulonephritis

Answer 379

1 GFR > 90ml/min 2 60 3A 45 3B 30 4 15 5 <15 + A1 albuminuria < 3mg/mmol A2 3-30 A3 >30

Answer 380

Urine albumin to creatinine concentration

Answer 381

Uncomplicated UTI Infection of urinary tract by a usual pathogen in a person with a normal urinary tract and normal kidney function Complicated UTI UTI where one or more factors that predispose to persistent or recurrent infection or treatment failure are present Recurrent UTI Relapse: same strain organism within 2 weeks of treatment Reinfection: further UTI more than 2 weeks after treatment Recurrent: ≥2 in six months or ≥3 in 12 months

Answer 382

Pregnancy DM RF Hospital acquired Obstruction

Answer 383

Lower UTI: infection confined to bladder or lower part of urinary tract (Urethritis inflammation (infection) of urethra) (Cystitis inflammation (infection) of the bladder) Upper UTI: infection extending to upper part of the urinary tract that includes the kidneys and the ureters (Pyelonephritis inflammation (infection)kidneys/ureters)

Answer 384

Peristalsis within ureteral SM propels urine towards bladder Ureters enter bladder wall at oblique angle ends compressed as bladder fills to prevent back flow of urine. Force of ureteric peristaltic contraction can overcome this to ensure urine flow is towards bladder. Exit from bladder guarded by internal and external urethral sphincter Normal skin flora Normal vaginal flora in females (lactobacilli produce acidic pH) Bactericidal activity of prostatic secretions in males Urine: urea, organic acids, polyamines, low pH, extremes of osmolality Glycosaminoglycan layer overlying bladder epithelium

Answer 385

Lower: Dysuria Frequency (nocturia) Cloudy urine Urgency Suprapubic pain +/- haematuria Upper: May or may not have cystitis symptoms plus: Fever (>380C) Chills Flank pain Renal angle tenderness Nausea/vomiting

Answer 386

Nitrite + strongly suggestive of enterobacteriaceae (convert urinary nitrate to nitrite) Leucocyte esterase + may be used to assess presence of white cells (pyuria) Nitrite +ve and leucocyte esterase +/- >90% will have a UTI Nitrite –ve and leucocyte +ve ~50% will have a UTI Nitrite –ve and leucocyte –ve 5% will have a UTI

Answer 387

Use dipstick when: female has few or mild-moderate symptoms and signs of cystitis (if typical symptoms - treat anyway so dipstick not needed) male has mild or non-specific symptoms of UTI as negative dipstick can safely exclude UTI Do not use dipstick: To diagnose UTI in the presence of indwelling catheter To screen for asymptomatic bacteruria in pregnancy Age >65 (PHE advice)

Answer 388

GI tract main reservoir uropathogens Enterobacteriaceae E. Coli: 90% Outpatient, 50% Inpatient Others: Enterobacteriaceae: Proteus can be associated with stones (urease) Klebsiella can be associated with stones (urease) Staphylococcus saprophyticus Enterococcus Faecalis Increased frequency elderly men with prostatism, or catheterisation/instrumentation Catheter related infections E. Coli, Proteus, Pseudomonas Aeruginosa, Candida True polymicrobial UTI observed in very few clinical situations Catheter/Stone disease Stagnant urine Colovesical fistula Haematogenous seeding to urinary tract most commonly observed with bacteraemia due to : Staph Aureus Pseudomonas Aeruginosa Salmonella Sp

Answer 389

Uncomplicated Lower UTI treat for 3/7 female, 7/7 male: Nitrofurantoin 100mg BD (or 50mg QDS) Trimethoprim 200mg BD Pivmecillinam 400mg stat then 200mg TDS Fosfomycin 3g sachet, single dose Complicated Lower UTI treat for 7/7 female and male: Ensure check urine culture and sensitivity after 48 hours Upper UTI (Evidence of UTI in patient with loin pain temp>380C: No allergy Allergy Cefuroxime 1.5g TDS Ciprofloxacin 400mg BD +/- +/- Stat dose IV gentamicin Stat dose IV gentamicin Aim PO after 48-72 hours Aim PO after 48-72 hours Total 7-10 /7 Total 7-10/7

Answer 390

PCT has high permeability Tight junctions/Huge surface area/microvilli/carbonic anhydrase etc Filtered solutes and water are reabsorbed here - tubular fluid here is iso-osmotic to plasma Uses 80% of total energy need of kidneys

Answer 391

PCT reabsorbs: ~ 65% of Na+, Cl-, K+ , water & solutes 100% glucose and amino acids All processes are linked to active Na+ reabsorption First half of PCT Na+ with glucose, AA, phosphate, lactate and HCO3- The filtrate entering the late PCT contains very little HCO3- and solutes (e.g. glucose, AA and PO4) Second half of PCT Na+ primarily with Cl-

Answer 392

Basolateral and Apical (luminal ) membranes Na+ moves across the apical membrane down an electrochemical gradient set up the Na+ K+ ATPase Na+ moves across the basolateral membrane against the electrochemical gradient via the Na+ K+ ATPase It uses both transcellular and paracellular routes

Answer 393

Na+ ion is reabsorbed mainly with Cl- ion in the second half of the PCT via an the electrochemical concentration gradient favouring passive Cl- reabsorption Cl- ions are reabsorbed both transcellularly and paracellularly Antiport systems (e.g. HCO3- are exchanged with Cl-) are also used

Answer 394

Solute reabsorption sets up an osmotic gradient for water reabsorption paracellularly across tight junctions transcellularly via water channels (aquaporin-1, AQP1) on apical & basolateral membranes A oncotic gradient created by unfiltered plasma proteins in the blood aids water reabsorption. Water reabsorption is important for solvent drag - ensuring dissolved solutes are reabsorbed

Answer 395

Water and Na+ reabsorption concentrates urea in the lumen and it is passively reabsorbed down its concentration gradient Urea transporters apical UTA1(CD) & UTA2 (LoH)

Answer 396

Dependent on sodium reabsorption - co transport Secondary active transport Increased with Amino acids and vitamins

Answer 397

SGLT2 - high capacity, low affinity (97%) SGLT1 - Low capacity, low affinity

Answer 398

Carriers can be saturated Tm is the max. rate at which the transporters can carry load Load = GFR x [X] plasma Renal threshold is the [X] plasma at which Tm is exceeded

Answer 399

H+ - All nephron K+ - DCT and CD

Answer 400

Osmolality: number of solute particles in 1 kg of solvent.

Answer 401

Osmolarity: number of solute particles per 1 L of solution

Answer 402

Dehydrated: Urine produced 0.3 ml/min 500 ml/day Hypertonic (< 1200 mOsM/L)

Answer 403

Countercurrent multiplier: sets up a cortex-medullary osmotic concentration gradient Descending limb: Impermeable to NaCl Permeable to water Ascending limb: Active NaCl transport Impermeable to water

Answer 404

Tubular urea is concentrated by ADH ADH activates a facilitated urea transporter UTA1 and UTA3 in the collecting duct. UTA2 transporter aids urea secretion in the descending limb Trapped & recycled – increasingly concentrated for elimination and maintains high medullary concentration

Answer 405

Supplies the medullary metabolic needs and maintains the cortex-medullary osmotic concentration gradient Plasma flowing down becomes more hypertonic as water diffuses out and solutes from the interstitium diffuse in. vice versa

Answer 406

Distal ascending loop

Answer 407

Stimuli - increase in osmolarity, decreased BP, decreased atrial stretch Released by the neurosecretory cells of the supraoptic and paraventricular nuclei of the hypothalamus and stored in the axon terminals in the posterior pituitary Travel to kidney and bind to V2 => inserts Aquaporin2 into late DCT and CD; This increases water retention. ADH also acts to reduce sweat loss and arteriole constriction Maximises vertical osmotic gradient: Stimulates triple co-transporter on the ascending loop Enhances urea reabsorption (via UT-A1) Vasoconstricts vasculature during haemorrhage/dehydration: Activates V1 receptors via increased phosphoinositide and calcium Skin & splanchnic circulation

Answer 408

alcohol, α-adrenoceptor blockers glucocorticoids

Answer 409

Hypoxia, pain, stress, emesis, hypoxia, exercise, hypoglycaemia, nausea morphine, nicotine, cholinergic agonists, β-adrenoceptor blockers angiotensin prostaglandins

Answer 410

Thirst centre in the anterior hypothalamus is close to supraoptic and paraventricular nuclei Contains osmoreceptors distinct from the ADH osmoreceptors Relays impulses to the cerebral cortex giving conscious sensation Thirst sensation is reinforced by dry mouth/throat

Answer 411

Polydipsia Excessive thirst – hyponatremia. Psychogenic polydipsia – mental illness (schizophrenia or OCD) Hypodipsia Partial deficiency of the thirst mechanism leading to inadequate water intake or inability to access fluid e.g. patient with dementia, stroke, critically ill - hypernatremia Adipsia Absence of thirst – trauma? Rare

Answer 412

neurogenic (central) diabetes insipidus Hypothalamic or pituitary defect - failure to produce ADH lack Desmopressin (ADH analogue acts of V2 receptors) nephrogenic diabetes insipidus Renal inability to respond normally to ADH Acquired (e.g. lithium, infection - pyelonephritis, cancers, polycystic kidneys) or inherited (e.g. AQP2 mutations) Polydipsia and polyuria

Answer 413

Dehydration: High urine Na - diuretics, addisons Low urine Na - Extra renal losses (GI, Skin) Euvolaemia SIADH(high urine osmo x2 serum, >200 and urine Na >40mmol/) Psychogenic polydipsia (very low urine osmo) Hypothyroidism Oedema Urine Na will be low (<20mmol/l) Perceived hypovolaemia- RAAS and ADH increased imbalance of these causes low Na Seen in: Heart failure, Cirrhosis, Nephrotic syndrome

Answer 414

Destruction of the adrenal glands Lack of aldosterone (and also glucocorticoids) Results in excess naturesis Clinical features: Hyponatraemia Hyperkalaemia Hypotension Hypoglycaemia Pigmented (ACTH)

Answer 415

No oedema* Reduced plasma osmolality Inappropriate urine Osm for serum (>300)** Urinary Na >40 Normal acid-base, K+, adrenal and thyroid function (Relatively) preserved renal function

Answer 416

If plasma Na+ <120 mmol/L Urgent assessment, high mortality The speed of onset determines rate of correction Neurological damage if corrected too rapidly Central pontine myelinosis Repeated checking is essential – aim to increase plasma Na+ by maximum of 10mmol/day

Answer 417

Hypovolaemia (most common) Lost disproportionately more water than salt Inappropriate iv fluids Osmotic diuresis (diabetic coma) Diabetes insipidus Reduced sodium excretion (rare) Conn’s syndrome (hyperaldosteronism)

Answer 418

Crystalloids Sodium chloride solun (normal saline = 0.9% saline = 154mmol/L) Hartmann’s (Na+ 131mmol, lactate 29mmol, K+ 5mmol) Dextrose solution (5% dextrose) Plasmalyte

Answer 419

Vulnerable to: Vascular disease,Immunological disorders, Deposition of foreign material (amyloid) It reacts by: ▪ Proliferation of endothelial cells (decreased flowoliguria, uraemia) ▪ Proliferation of mesangial cells and or matrix ▪ Thickening of glomerular basement membrane ▪ Alteration in podocyte processes (effacement) ▪ Capillary necrosis (fibrinoid) ▪ Crescent formation

Answer 420

forms the central region of the renal glomerulus and provides support to the glomerular tuft is separated from the vascular compartment by a fenestrated endothelium without an intervening basement membrane

Answer 421

Global – the entire glomerulus is affected B. Segmental – only part of the glomerulus is affected C. Diffuse – all glomeruli are affected D. Focal – only a proportion of glomeruli are affected

Answer 422

▪ Increase in glomerular permeability and consequent loss of plasma proteins (mainly albumin) in the urine ▪ Proteinuria (>3.5g/day) ▪ Protein:creatinine ratio >300-350 mg/mmoL = nephrotic range proteinuria ▪ Serum shows Hypoalbuminemia (< 30 g/L) (as a result of proteinuria) ▪ Patient is oedematous ▪ Hyperlipidaemia and lipiduria

Answer 423

Oedema due to: ▪ hypoalbuminaemia and consequent reduction in colloid osmotic pressure allowing accumulation of fluid in the interstitium ▪ Activation of RAAS, the SNS and reduction of natriuretic factors to increase sodium and water retention as a result of decreased blood volume Dyspnoea due to pleural oedema and effusion; ascites Increased infection (due to loss of immunoglobulin and complement in the urine) Increased atherosclerosis (due to hyperlipidaemia -LDL and triglycerides) Low levels of hormones (thyroid) and ions (iron, zinc) due to decrease in binding proteins Thromboembolic events due to loss of balance of coagulation and anticoagulation factors

Answer 424

Most commonly occurring nephrotic disease in the population Effacement of podocyte foot processes ▪ Nephrotic disease in children <10 years ▪ Heavy proteinuria primary Nephrotic syndrome ▪ Most common to be found affecting Child/Adolescence ▪ Responds to steroids ▪ Usually no progression to renal failure

Answer 425

* Primary Nephrotic condition * Focal and segmental * On EM see podocyte effacement like in minimal change * Glomerulosclerosis = increased collagen deposition i.e. Mesangial MATRIX 50% will progress to kidney failure in 5-10yrs

Answer 426

Commonest cause of primary nephrotic syndrome in adults * Rule of thirds - spontaneous resoltuon, persistent proteinuria, Progression to ESRF * IgG Immune and C3 complex Autoimmune antibody against phospholipase A2 Receptor (PLA2-R deposits (antibody/antigen) causing membrane thickening complexes deposited in the subepithelial space (between podo and BM)

Answer 427

▪ Proliferative ▪ Inflammatory ▪ Acute inflammation of the glomerulus ▪ Damage capillary walls (red cell casts in urine) ▪ Occlusion of capillary lumen (proliferation of cells and influx of inflammatory cells) ▪ Clinical manifestations: ▪ haematuria, ▪ Decreased GFR leading to hypertension and oedema ▪ Oliguria, azotemia ▪ Examples include: ▪ Acute postinfectious GN ▪ SLE (secondary)

Answer 428

Commonest GN * Idiopathic * Any age * Classically present with visible/invisible haematuria * Relationship with mucosal infections * Variable histological features & course * +/- proteinuria * Significant proportion progress to renal failure * No effective treatment Deposits in the mesangium

Answer 429

Diffuse ▪ Swelling and proliferation of endothelial cells and mesangial cells: occlude lumen and allow red cells into filtrate ▪ Infiltration of neutrophils and monocytes ▪ Mainly post strep infection (throat) but also viral (mumps) and staph ▪ Immune complexes develop post infection (1-4 weeks) and are deposited in the mesangium and BM (IgG and C3) - subepithelial ▪ Haematuria (cola coloured urine), mild hypertension and oliguria, proteinuria ▪ Most often in children. Treat with antibiotics. Prognosis good in children

Answer 430

Anti GBM ▪ is a disease that occurs as a result of injury to small blood vessels (capillaries) in the glomerulus ▪ targeted to the basement membrane of kidney and/or lung ▪ Auto Ab’s recruit complement and lymphocytes which damage capillaries ▪ Leads to proliferation and accumulation in Bowman’s space (Parietal epithelium of Bowman’s capsule) . ▪ About half of people with anti-GBM disease have lung involvement.

Answer 431

Group of systemic disorders * Nephritic presentation (RPGN) * Rapidly progressive glomerulonephritis (RPGN) characterized by a rapid loss of kidney function, (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months) with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies * Association with Anti Neutrophil Cytoplasmic Antibody (ANCA) * No immune complex/antibody deposition * Antibodies are inside the cytoplasm

Answer 432

▪ Wagener's disease (GPAGranulomatosis with polyangiitis

Answer 433

Hypo -> shallow T, prominent U Hyper -> Flat P, QRS widening, Tall tented T waves

Answer 434

10ml of 10% calcium gluconate i.v. Stabilises cardiac myocytes

Answer 435

Na/K+ ATPase: Normally drives K+ into cells Inhibition by hypoxia/drugs, Trauma, infection, cell lysis, severe exercise (cell breakdown), Rhabdomylosis leads to hyperkalaemia Pseudohyperkalaemia on mishandling blood Insulin causes uptake into skeletal muscle and liver cells Ingestion of K+ therefore balanced with an increase in uptake Insulin and glucose is an emergency treatment for hyperkalaemia Catecholamines/ephinephrine β2 adrenoceptors – increase cellular uptake. This is inhibited by β-blocking drugs Plasma osmolality e.g. Hyperosmolality resulting from hyperglycaemia in insulin deficiency H2O moves out of cells and brings K+ with it (solvent drag) Acid-base balance e.g. metabolic acidosis leads to hyperkalaemia as extracellular H+ exchanges for intracellular K+ Required to maintain electroneutrality

Answer 436

PCT: Most K is reabsorbed by paracellular diffusion (solvent drag) Driven by active Na+ reabsorption Fluid becomes slightly +vely charged – also helps Ascending tubule: K+ reabsorption occurs both transcellular and paracellular routes Na-K-2Cl pump – secondary active transport +ve luminal voltage – drives paracellular K movement DCT: where K+ secretion begins Two types of Na channel Thiazide sensitive Na-Cl channel in early DCT ENaC in late DCT Renal outer medullary small-conductance K+ (ROMK) present – secretes K+ ENaC in late DCT is sensitive to aldosterone Collecting duct - principle cell for K secretion Driven by basolateral Na-K-ATPase – high intra-cellular K drives diffusion into the lumen, opposite effect for Na

Answer 437

K+ pumped in and Na+ pumped out of the cell by the basolateral Na-K-ATPase pump The low intracellular Na+ favours entry of Na+ into cells via selective sodium channels in the apical membrane (ENaC) High intracellular K+ and electronegative lumen (because of Na+ absorption) favours K+ secretion via potassium channels (ROMK and BK) in the apical membrane. Aldosterone (Aldo) increases both the number of open sodium channels and the number of Na-K-ATPase pumps.

Answer 438

Secretes H+ and reabsorbs HCO3- & K+ No basolateral ATPase but have apical H+ ATPase pumps - relies on cellular-luminal H+ gradient K+ is reabsorbed - linked to the H+ K+ ATPase antiporter HCO3- is reabsorbed - linked to Cl-

Answer 439

In metabolic acidosis, H+ secretion is increased and net K+ secretion is reduced (more K+ reabsorption in intercalated cells). This favours K+ retention (hyperkalaemia). Acidotic patients will have high plasma [H+] and high rates of delivery of H+ to the kidney H+ load causes increased K+ reabsorption (therefore reduces overall K+ excretion) and ECF [K+] rises. In alkalosis, the converse is true

Answer 440

First action in setting of hyperkalaemia with ECG changes: 10ml of 10% calcium gluconate i.v. Stabilises cardiac myocytes Doesn’t change serum K+ Short-term holding measures shift potassium into cells Insulin-dextrose (e.g. 5-10U of insulin plus 500ml of 10% dextrose) Effect only lasts 4-6hrs, then serum potassium ‘rebounds’ as K+ starts to come back out of cells Correct acidosis Shifts potassium into cells Increases net K+ secretion (intercalated cells) Sodium bicarbonate (e.g. 500ml of 1.4%) Increase potassium excretion Increase tubular flow and distal sodium delivery IV fluids (e.g. normal saline) to correct hypovolaemia Loop diuretics if patient fluid overloaded Dialysis Reduce potassium intake Dietary change Potassium binders (sodium zirconium, patiromer)

Answer 441

Acidosis: Diarrhoea Renal tubular acidosis Renal failure Diabetes Tissue hypoxia Drugs (e.g. ethanol, salicylate) Alkalosis Persistent gastric vomiting Gastric suction Antacids Hyperaldosteronism Chronic hypokalaemia Diuretics

Answer 442

PCT HCO3- + H+ turns to H2O and CO2 so it is permeable to tubular cells. Bicarb reforms in cell and moves into blood via Sodium bicarbonate symporter H+ then diffuses back to lumen with soidum going in opposite direction

Answer 443

CD α -Intercalated cells secrete H+ and reabsorb HCO3- & K+ No basolateral ATPase but have apical H+ ATPase pumps Activity depends on the cellular H+ gradient K+ is reabsorbed - linked to H+ K+ ATPase antiporter HCO3- is reabsorbed - linked to Cl-

Answer 444

1/3 of acid load excreted using Phosphate HPO42-/H2PO4- (trapped form) and creatinine buffers 2/3 of acid load excreted using ammonia NH3/ammonium (trapped form) buffers

Answer 445

From glutamine -> NH4 and HCO3- NH4 -> NH3 and H+ NH3 diffuses out and then reforms NH4 (trapped)

Answer 446

It is reabsorbed by thick limb of Loop into the medullary interstitium where it exists as NH4+ and also NH3 The Collecting Duct IS permeable to NH3 it diffuses into CD lumen via 2 glycoproteins (Rhesus) . H+ actively secreted into the lumen interacts to form NH4+ is trapped for excretion as the CD is impermeable to it.

Answer 447

Acidosis causes hyperkalaema & vice versa. H+ enters cells and K+ exits keeping electroneutrality. Changes in K+ homeostasis Hyperkalaemia inhibits NH4+ production and the high levels compete with NH4+ at the triple cotransporter, so NH4+ excretion is impaired Hypokalaemia increases NH4+ production and H+ secretion is increased This is linked with increased HCO3- reabsorption. Changes in Na+ homeostasis e.g. ECF volume contraction increases Na+ reabsorption, H+ secretion and HCO3- reabsorption Aldosterone stimulates H+ secretion in the intercalated cells and can also exaggerate the K+ effect. Parathyroid hormone inhibits the Na+/H+ exchanger.

Answer 448

Glomerulus allows only small amounts of low molecular weight proteins into tubular fluid (500-1500mg/d) Most filtered protein reabsorbed and catabolized by tubule cells in PCT (net excretion 40-80mg/day) Loop of henle Tubule cells secrete Tamm-Horsfall glycoprotein

Answer 449

Transient proteinuria in the absence of renal disease Fever, acute illness, exercise, angiotensin II or noradrenaline infusion Orthostatic Proteinuria Proteinuria while upright Mild (<1g/day) Mainly in adolescence; resolves by 30y Mechanism probably  glomerular pressure

Answer 450

Increased plasma concentration of filterable proteins Immunoglobulin light or heavy chains – multiple myeloma, plasma cell dyscrasias B2 –microglobulin - malignancy

Answer 451

Most common and most important to detect Wide range of glomerular disorders Podocyte disorders: minimal change disease; Focal and segmental glomerulosclerosis (FSGS) Immune complex mediated glomerulonephritis Secondary glomerulopathies: diabetic nephropathy; amyloidosis

Answer 452

Decreased tubular reabsorption of filtered proteins Tubulointerstitial nephritis (drugs, idiopathic) Toxic injury to tubule cells (gentamicin, cadmium, lead) Metabolic - hypokalaemia Hereditary diseases (Wilson’s disease) Fanconi syndrome

Answer 453

Type IV Collagen

Answer 454

Lost Ig -> Increased infections Loss of coag proteins C and S -> Thromboembolism hypalbuminaemia -> increased fibrogen, hyperlipidaemia

Answer 455

Genes PKD1/2 code for calcium channels for both and flow sensing in PKD1 Possible Derangements Leading to Cyst Formation 1 Abnormalities in Ca channels 2 cAMP Fluid secretion into cysts (CFTR channel) Epithelial proliferation 3 Polycystins located in the cell membrane and/or cytoplasm interact with oncogenes/mitogens (mTOR, Jak/STAT, Wnt/β-catenin) 4 Inability of abnormal cilia to detect luminal flow Decrease in Ca Transport Abnormal Ca flux leads to epithelial proliferation due to cAMP signalling 5 Abnormal cilia on centrosomes

Answer 456

PKD1 53 yrs PKD2 73 yrs

Answer 457

Age (+age of onset in relatives) Male gender PKD1 > PKD2 (truncation PKD1 mutation) Macroscopic haematuria (or any urinary tract manifestations before age 35 yrs) HT Large kidneys TKV>1500ml

Answer 458

Vasopressin Receptor Antagonist – tolvaptan Somatostatin Analogue - octreotide Inhibit Cell proliferation – sirolimus/everolimus Cyst drainage Statin Control of hypertension Protein restriction Ammoniagenesis and alkali therapy

Answer 459

Defect of Na resorption in loop of Henle Hypokalaemia, metabolic alkalosis, raised renin and aldosterone, JGA hyperplasia

Answer 460

Defect of Na resorption in distal tubule Hypomagnesemia, hypokalaemia and hypocalcuria

Answer 461

Neutral Na balance maintained until advanced renal failure Decreased Glomerular filtration of Na compensated for by decreased tubular reabsorption, resulting in increased fractional excretion of Na (FENa 1/ GFR) Decreased Tubular Na reabsorption occurs largely in loop of Henle, DCT and collecting duct Na excretion also increased by ANP Also impaired Na conservation – Na restriction -> net Na loss Consequences: Na and water retention Hypertension Oedema Treatment: Loop diuretic

Answer 462

To maintain neutral balance, must have increased K excretion per nephron due to less nephrons Almost all filtered K is reabsorbed in PCT and LoH Increased K excretion must depend on increased K secretion in the collecting duct Patients with CRF prone to hyperkalaemia, especially with ACEI, spironolactone or trimethoprim

Answer 463

In CRF Decreased ammoniagenesis in PCT Some decreased titratable acid excretion Some decreased bicarbonate reabsorption Distal urine acidification preserved Metabolic acidosis Treatment: oral bicarbonate supplementation

Answer 464

Serum phosphate preserved until GFR <20ml/min Achieved through increased reabsorption in PCT

Answer 465

Uraemic toxin(s)” - most likely a small molecule(s) - products of protein catabolism Urea a useful marker but is probably not the “uraemic toxin” “Middle molecules” – small polypeptides – role controversial

Answer 466

Decreased Capacity to produce dilute urine Decrease Capacity to excrete water load Obligatory solute excretion = 600mOsm/day Normal kidney can dilute urine to 30mOsm/l -> Excrete up to 20L of urine per day Moderate CRF maximum dilution 160mOsm/l -> Excrete only 3.8L of urine per day Patients with CRF prone to hyponatraemia

Answer 467

max urine concentration = 1200mOsm/l -> Can excrete obligatory osmolar load in 500ml Max urine conc decreased in CRF – 400mOsm/l -> Excrete obligatory load in min 1500ml Mechanisms Increased solute load/nephron – osmotic diuresis Loss of medullary hypertonicity Resistance to ADH Patients prone to dehydration, nocturia

Answer 468

Failure of 1-hydroxylation of vitamin D results in decreased intestinal Ca absorption  hypocalcaemia Failure of renal phosphate excretion  hyperphosphataemia

Answer 469

Consequence of Ca / P and PTH Abnormalities High turn-over: Osteitis fibrosa cystica Low turn-over: Adynamic bone disease Vascular calcification Increased mortality Other PTH effects decreased response to epoetins decreased immune response

Answer 470

Typically normochromic, normocytic Mechanisms: deficient renal production of erythropoietin functional iron deficiency EPO resistance

Answer 471

Iron deficiency – absolute or relative Decreased Hepcidin from liver Infection or inflammation Severe hyperparathyroidism Vitamin B12 or folate deficiency