Endo Flashcards

Question

# HI Descrieb causes of pelvic inflammatory disease | Yr2, exam, own notes

Answer 1

Anatomical relationships #clinicallyrelevant for two key reasons: - pathogens can spread retrogradely from vagina to peritoneal cavity. Examples include pelvic inflammatory disease e.g. pelvic peritonitis or general peritonitis, as well as salpingitis from peritoneal infections Spectrum of STI presentations e.g. Trichomonas, Chlamydia, Neisseria - Asymptomatic infection - Lower genital tract symptoms (vaginal/urethral discharge) - Upper genital tract symptoms (pelvic inflammatory disease

Answer 2

Type I Diabetes Mellitus - Characterized by - Pancreatic β cell destruction and ultimately absolute insulin deficiency - T cell-mediated - Presence of autoantibodies (directed against pancreatic islet cells) - Glutamic acid decarboxylase (GAD), protein tyrosine phosphatase (IA2), zinc transporter 8 and insulin (IAA) - Presence of one or more antibodies can precede clinical onset by many years (presence of all three close to 100% risk of developing clinical diabetes) - No evidence that these autoantibodies are pathogenic - Inflammatory response within the pancreatic islet cells "insulitis" - Mononuclear cell infiltrate with predominantly CD8+ cells (CD4 + T cells and macrophages) - observed in early diabetes - Increased expression of Class I MHC and aberrant expression of class II MHC on beta cells - Progressive pancreatic β cell destruction (size and number) - mediated by autoreactive CD4+ T cells - lysis by cytotoxic T cells - local production of pro-inflammatory cytokines and ROS - evidence for defects in Treg function - overt diabetes only occurs once most of these cells have been destroyed - During fasting or otherwise in the absence of insulin (type 1 diabetes), hormone-sensitive lipase in fat cells is activated. - This results in hydrolysis of stored triglyceride into glycerol and fatty acids. - β-oxidation of fatty acids in mitochondria results in excess formation of ketone bodies. - Associated with this is the development of metabolic acidosis. Investigate: plasma glucose, HBA1C, OGTT, c peptide (Bedside: Urinalysis, urine dipstick, fundoscopy, diabetic foot Ex, BP Bloods: FBC, EUC, LFT, cholesterol studies Special tests: Anti-GAD Ab (T1DM) -- common to both Insulin: ● Can be long-, intermediate-, or short-acting ● Common insulin regimens: ○ Basal-bolus – long-acting 1-2x a day with fast-acting boluses before meals ○ Premixed preparations – administered twice a day (25% short-acting, 75% long- acting) ○ Insulin pump – constant infusion of insulin, may be increased before meals ● Subcutaneous injection ● Requires electrolyte monitoring (esp. K+)

Answer 3

Clinical features: - gradual onset - mainly symptomatic initially - first presentation usually complications Common to both: Polyuria (excessive urination, +/- glycosuria) Polydipsia (excessive thirst, 2º to polyuria and dehydration) Polyphagia (excessive hunger) Fatigue, lethargy Blurred vision Poor wound healing Frequent infections Unexplained weight loss Mgmt: A1c target BP target Cholesterol Drugs (↓ CVD risk) Exercise + diet T2DM: Metformin Sulfonylureas DPP-4 antagonists GLP-1 agonists Thiazolidinediones SGLT-2 inhibitors A-glucosidase inhibitors

Answer 4

Microvascular - Diabetic retinopathy - Diabetic nephropathy - Diabetic neuropathy Macrovascular - Diabetes is a risk factor of atherosclerosis as chronic hyperglycemia creates a dysfunctional epithelium = impaired vasodilation, oxidative stress, pro-coagulative state and pro-inflammatory state - Major determinants are other metabolic risk factors i.e. obesity, dyslipidemia and arterial hypertension - Diabetics often have 1 or more of these risk factors - Coronary artery disease - this is a major cause of death in diabetics - Peripheral vascular disease - Cerebrovascular disease depending on location of atherosclerosis.

Answer 5

Summary of retinopathy: - Tends to occur in parallel to nephropathy - Same pathways affected, particularly affecting microvasculature at back of eye - Retinal ischaemia - Vascular permeability (leaky vessels causing macular oedema) - Hypertension may contribute Proliferative diabetic retinopathy (PDR) - Ischaemic retina releases VEGF, growth hormone, IGFR → all drive proliferative diabetic retinopathy - New vessels (in response to VEGF) and abnormal capillaries - Weak vessels prone to haemorrhage and fibrosis → retinal detachment → loss of vision - Retinal flurocene angiogram shows blushes - abnormal vessel formation due to ischaemic retina - Erythropoietin excreted in ischaemic retinopathy → retinal neovascularisation - Treatment: - laser to burn ischaemic parts → VEGF not produced - Anti-VEGF injections Non-proliferative diabetic retinopathy (NPDR) - Cholesterol-like material (hard exudates aka dots and blots) build up on retina → leaky vessels - Soft tissue oedema can affect central vision - Capillary weakness → micro-aneurysms or haemorrhages from breaks in capillaries - Important to have check ups every 2 years to exclude diabetic retinopathy - includes: - Visual acuity test - Retinal exam - Better results if picked up early

Answer 6

- Peripheral neuropathy: gloves and socks - Mononeuropathy: along dermatome - autonomic neuropathy: gut heart bladder --- Summary of neuropathy: - Peripheral neuropathy: painful feet that burn at night (doesn’t improve with diabetes control) - Longer the nerve, the more likely it will get damaged by diabetes - Mononeuropathy: one nerve damaged → can cause mononeuritis, multiplex or plexopathy (e.g. lumbosacral plexus affecting thigh) - Autonomic neuropathy: postural hypotension, nocturnal diarrhoea, trouble with bladder, etc. - Pathophysiology: - Hyperglycaemia and glycosylation involved - Oxidation of LDL - intracellular inflammation activated - Increased glucose causes ROS production - Interruption of microcirculation to single nerve e.g. diabetic CN3 palsy causing diplopia (eye goes down and out) - Pupil sparing occurs in diabetic - Principal treatment is to optimise glycemic control and pain management if applicable - Also key to assess feet: sensory, motor and any deformities/calluses/ulcers/infections - Additionally look for Charcot’s foot deformity = swollen flattened foot due to microfractures and collapse - Lipid lowering drugs shown to help decrease all microvascular complications especially diabetic neuropathy

Answer 7

Pathology: - Glomerulosclerosis and nodular sclerosis occurs - drop out of glomeruli - Mesangial thickening - Gloumerular capillaries lost - Tubules in kidneys also diseased with ↑ BM - Some epithelial cellular changes to tubules - Interstitial lesions and fibrosis → tubular atrophy - Early on, hyperglycaemia causes hyperfiltration ∴ eGFR ↑ and creatinine ↓ (changes in haemodynamics of kidney tissue) - As cellular damage occurs, eGFR ↓ → can then progress quickly to end-stage renal disease - Microalbuminuria arises → inspirent diabetic nephropathy - A smaller group of patients may not have albuminuria nephropathy - instead, often have hypertension → renal artery stenosis - Contributing factors: - Advanced glycosylation end-products (AGEs) - Protein Kinase C activates growth factors that lead to fibrosis, inflammation and albuminuria - High BP can contribute → ACEi and ARB antihypertensives may help Detect with urinalysis (proteinuria, microalbuminuria in early stage and macroalbuminuria in late stage). - Diabetic nephropathy progression: - Stage 1 = Hyperfiltration = increase in GFR and normal albuminuria - Stage 2 = Silent stage = Normal GFR and normal albuminuria - Stage 3 = Incipient stage = Normal GFR and microalbuminuria - Stage 4 = Overt stage = GFR decline and macroalbuminuria (additionally results in hypertension) - Stage 5 = End stage renal disease = GFR <15 and macroalbuminuria (hypertension)

Answer 8

The biochemical criteria for diagnosis of DKA are: Serum glucose >11 mmol/L Venous pH <7.3 or Bicarbonate <15 mmol/L Presence of ketonaemia/ketonuria Children with hyperglycaemia (Blood glucose level (BGL) >11 mmol/L) +/- ketosis who are not acidotic can be managed with subcutaneous insulin (see Diabetes mellitus, new presentation, mildly ill). Side Effects Different types ketones produced include B-Hydroxymutyrate, acetatoacetate and acetone Management The main aim in treating DKA is to progressively improve blood pH and clear the body of excessive ketones by aggressive fluid replacement and insulin therapy. - Assess Airway, Breathing, Circulation - IV Fluids - Normal Saline 0.9% NaCL (switch to 5% dextrose with 0.45% NaCl when serum glucose reaches ~15) - Insulin - Insulin infusion until pH stabilizes - Potassium - Administration of Insulin can cause hypokalemia, potassium levels should be checked prior to insulin administration - ABG assessment - assess pH and need for bicarbonate Monitoring: Check ABG, EUC every 4hours. Check Urine Glucose and Ketone 4hourly Check Blood glucose hourly. Monitor ECG for hypokalaemia/hyperkalaemia Monitor GCS regularly --- Pathophysiology of Diabetes Type II and Hyperosmolar state Overview Hyperosmolar Hyperglycaemia (HOH) state occurring primarily in type 2 diabetes and is characterised by marked hyperglycaemia and dehydration without ketoacidosis. The disturbance in consciousness in patients varies from drowsy to comatose. HOH is a more sinister complication than ketoacidosis with a mortality rate as high as 50%. Diagnosis - biochemical: - Hyperglycemia - Serum osmolality is high (>350 mmol/kg) - No acidosis - No ketonuria + on urine dip testing can occur with starvation and vomiting. Serum osmolality (in mosmol/kg) can be calculated if not available from the laboratory using the following equation: Osmolality = 2(sodium + potassium) + glucose + urea Pathophysiology This condition results from a combination of insulin deficiency and coun- terregulatory hormone excess. The insulin present stops ketone produc- tion but in insufficient quantities to prevent worsening hyperglycemia. Management Same as DKA, but with a few exception because patients are usually older. - IV Fluids - Normal Saline 0.45% NaCL (switch to 5% dextrose with 0.45% NaCl when serum glucose reaches ~15) - Insulin - Slow Insulin infusion until pH stabilizes - Potassium - Administration of Insulin can cause hypokalemia, potassium levels should be checked. - Antibiotics - if infection - ABG assessment - assess pH and need for bicarbonate

Answer 9

1. Unrestricted carbohydrate intake in the last 3 days prior to test 2. Avoid excessive exercise before test 3. OGTT should not be performed on hospitalised, acutely ill or inactive patients 4. Discontinue, when possible, meds known to affect glucose tolerance e.g. corticosteroids, beta-blockers, diuretics, antidepressants 5. 10-14 h o/night fast the night before the test 6. No cigarettes/coffee/tea 7. Perform test in morning 8. Patient should remain seated during test

Answer 10

Investigations of an infertile couple ^[potential exam question] - try and treat couple and see them together - take full medical history from both - family history may be relevant - genetic conditions - consider potential impact of medicaitons on male and female fertility - consider weight and lifestyle factors Gynaecological history * Menstrual cycle - how many days * Symptoms of PCOS - oily skin, hirsutism, weight gain * Symptoms of endometriosis - pain in periods, between periods, sex, bowel movements * Past history of STIs * Past obstetrics history * Past gynaecological surgery * Past fertility treatment Female investigations * Cervical screening * Antenatal screen * Hormone day 2: LH, FSH, prolactin, TFT, FAI ^[PCOS raised], SHBG ^[down in PCOS], testosterone ^[free fraction increases] for baseline ovarian reserve and assessment of PCOS (also rubella?) * Day 21: estrogen, progesterone to confirm ovulation * Antimullerian hormone * Pelvic ultrasound for anatomical survey, tubal patency (Hycosy), antral follicle count and signs of endometriosis * Or Hysterosalpingogram ( Xray ) for tubal patency Male investigations * Semen analysis: “SFA + IBT” = Volume, concentration, motility, morphology and antisperm antibody screen * Do not rush in to repeat semen analysis if initial abnormal, wait 12 weeks to repeat (Refer to a dedicated andrology laboratory) * FSH, LH, testosterone, thyroid function and prolactin if oligospermia AMH test – Can perform anywhere in menstrual cycle – OCP or any hormonal contraception may reduce level – Some intra-individual variation : best to repeat if big decisions are about to be made on it * Shall I order it? – Will it change behaviour or management – Careful counseling especially in single women – What would you do if it’s normal – What would you do if it’s abnormal

Answer 11

Menopause - **Definition**: The permanent cessation of menstruation **resulting from the loss of ovarian follicular activity. - Natural menopause is recognized after 12 consecutive months of amenorrhea, with no other obvious pathological or physiological cause. - **Median Age**: ~51 years - Menopause is a retrospective clinical diagnosis (World Health Organisation 1994) Extra notes: * Surgical menopause: removal of both ovaries (any age) * Premature ovarian insufficiency (PO): cessation of ovarian function before age of 40 (↑ risk of CVD, dementia and osteoporosis) * Permanent loss of ovarian follicular developement * Loss of cyclical production of estradiol, progesterone and testosterone - may/may not result in symptoms Premature Ovarian Insufficiency - Cessation of ovarian function 2 standard deviations **prior to the population mean age of menopause.** - i.e., 2 X SD prior to 51.5 years - Practical definition: Before the age of 40 years

Answer 12

**Hormonal Contraception** - Exogenous hormone effect on endometrium: - Stroma appears pseudodecidualised – polygonal cells with abundant eosinophilic cytoplasm with central vesicular nuclei 1. COMBINED ESTROGEN/PROGESTOGEN CONTRACEPTIVES - Prevention of ovulation is the dominant mode of action via synergistic (E + P) suppression of LH surge/ovulation and FSH (follicle development) - e.g. COCP (combined oral contraceptive pill) - Risks: thrombosis, HTN, vascular events (stroke/MI), liver adenoma, ?increased breast cancer/cervical cancer - Benefits: regular, less heavy periods, acne, prevention of ovarian and endometrial cancer, ?decreased bowel cancer, decreased all-cause mortality 2. PROGESTOGEN-ONLY CONTRACEPTIVES - suppression of the LH surge and ovulation (variable efficacy) - viscous and scant cervical mucus to deter sperm penetration - prevention of endometrial growth and development - prevention of implanatation - reduction in cilia motility and muscular peristalsis pereventing transport of ovum - e.g. norplant, minipill, morning after pill, depo-provera Progesterone Only Pill (POP) (Mini-pill) - Levonorgestrel or norethisterone, drosperinone (long acting) - Traditionally short-lived effect (max 27 hours). "3-hour window," however new formulation 24 hours! - Easy to start and stop - Generally does not interfere with the cycle, however, drosperinone tends to cause amenorrhea Progesterone Injection "Depo" - Depot injection (medroxyprogesterone acetate) - IM injection buttock (or arm) - Every 12 weeks - May delay return to fertility - Lowers oestrogen – concern for low bone mineral density – older women Progesterone "Implanon" Implant - 3 years - Releases etonorgestrel - Inserted under the skin upper arm - Spotting early on Intrauterine Device (IUD) (Levonorgestrel) ("Mirena or Kyleena") - T-shaped device inserted into the uterus (by trained GP or specialist) - 5 years - Small amount progesterone **local action**, usually little in the way of side effects - Nulliparous or parous women n.b. Mirena higher dose, Kylena lower dose - more spotting 3. Barrier protection e.g. condoms - Stops sperm entering the vagina - Only contraception that provides protection from STIs (some) 4. Fertility Awareness - Tracking cycle with calendar, temperature, cervical mucous… - Avoiding fertile window 5. Copper IUD - Create toxic environment for sperm - Prevent implantation ## Footnote Sterilization - Vasectomy - Male vas deferens are cut and tied or sealed - Tubal ligation - clips put on the fallopian tubes - Tubal occlusion (Essure TM) metal coils in fallopian tubes - 1999 - 2017. Recalled in late 2017 due to adverse events.

Answer 13

**Managing Erectile Dysfunction** - **1970-90s Approaches:** - Vascular surgery, inflatable implants, injectable vasodilator drugs. - **NO's Role:** - Understanding the role of nitric oxide in vasodilation of erectile tissue. - action of sildenafil, initially developed for angina -- much more effective at vasodilation in penis - **Risk Factors:** - Hypertension, diabetes, high lipids, smoking. ^[CVS/PVS] - **Cavernous Nerve releases neurotransmitters** - this leads to the production of NO which diffuses into and enters smooth muscle cells - NO stimulates the conversion of GTP to cGMP - cGMP induces a chemical cascade - results in **reduced intracellular calcium** and smooth muscle relaxation - note: PDE5 coverts cGMP to GMP, switches off this effect - sildenafil inhibits this enzyme to prolong relaxation/vasodilation **Challenges in Erectile Function** - **Importance to All Genders - Note: Orgasm and ejaculation possible with partial erections. - **Causes of Dysfunction:** - Age-related, reduced arterial flow (in large and small vessels, atherosclerosis, diabetes), veins leaking, nerve damage, Peyronne’s disease (fibrous plaques impinge on erectile tissue of penis) - **PDE5 Inhibitors:** - Only males benefit - **Retrograde Ejaculation:** - Associated with: - age - alpha-adrenergic blockers - diabetes - damage to sympathetic chain or presacral nerves - urethral strictures (STIs uncontrolled; trauma) - congenital abnormalities - prostate surgery damages the internal sphincter or nerves **Rapid Ejaculation and Its Causes** - 13% of men attending clinics for sexual problems: physiological variation (neurological input leading to shorter plateau) OR anxiety/sympathetic overdrive - primary or secondary occurrence (SSRIs and tricyclics) - **Associated with:** - Anxiety - ED may precede it - low libido - Relationship problems - expectations not met - **Intravaginal Ejaculation Latency Time** - **Measurement:** - Time from vaginal intromission to ejaculation. - **Study Findings:** - Range from 0.55 to 44.1 minutes, with a mean of 5.4 minutes. - **Categories:** - Rapid ejaculation (<1 min), probable rapid ejaculation (1.5), not rapid ejaculation (>2). Note that short time to orgasm also occurs in females, but is not well studied. **Delayed Orgasm & Anorgasmia** - **Causes:** - Nervous system dysfunction e.g. MS, diabetes - drug-related: SSRIs, antipsychotics - psychological factors - reduced/different/inadequate stimulation Treatment: SSRIs

Answer 14

Parathyroid glands Location Typically 4 glands located on the posterior aspect of thyroid gland. Note that there can be more than four spread in the mediastinum as low as the heart -- which can be hard to find in removal surgery. Macroscopy - About 6 mm diameter - 0.2g in females, 0.3 g in males Microscopy At low power, endocrine epithelial cells and adipose tissue can be seen. It is encased by a thin capsule ^[comp?]. Endocrine cells are scattered in clusters throughout adipose. Endocrine epithelial cells can be divided into active chief cells and inactive oxyphilic cells. Chief cells are the most common cell type in the PT gland. The nuclei are round and centrally located. The cytoplasm is homogeneous. The chief cells are arranged in cords or plates, and surrounded by capillaries. The function of chief cells is to secrete PTH. Oxyphil cells present as groups or nests of cells. They are larger than chief cells, and have an eosinophilic cytoplasm. The function of oxyphils is not known. Function Chief cells of the parathyroid gland secrete PTH. Its function is to increase blood calcium concentration by increased calcium removal from bones, and increasing calcium taken from diet, and decreasing calcium excreted in urine. --- Location The pancreas is located behind the stomach. Macroscopic Can weigh 80g on average in males (60-100g). Can weigh between60 and 250g in females. Consists of a head, neck, body and tail. Microscopy At lower power, extensive small, dense clusters of acinar cells can be seen, as well as occasional larger clusters of lighter staining cells of islets of Langerhans. - The islets of Langerhans are 100-200 u in diameter - There are about 1 mil. islets in the pancreas - Histologically they appear as cords of cells separated by capillaries. - They are clustered less dense but are larger clusters, and do not associate with ducts - There are four cell types in islets that cannot be histologically distinguished from each other, only via IHC: - beta cells which secrete insulin (60-80%) - alpha cells which secrete glucagon (20%) - delta cells which secrete somatostatin - very few in number - F cells secrete pancreatic polypeptide - also few in number Function The pancreas has both endocrine AND exocrine function. The acinar cells are exocrine and produce pancreastic secretons, which are transported by pancreatic ducts to the ampulla. The islets of langerhans have endocrine function, and produce glucagon, insulin and somatostatin.

Answer 15

Location and general features The pituitary is located at the base of the brain. It is connected to the hypothalamus by a stalk or infundibulum. It is 1 cm in diameter. It sits in a bony cavity at the base of the skull known as the sella turcica. It weighs between 600 to 800 mg. Macroscopic appearance The pituitary gland can be broadly divided into three parts: - the anterior pituitary or pars distalis or adenohypophysis - the posterior pituitary or neurohypophysis or pars nervosa - the stalk or stem or infundibulum The anterior pituitary is larger than posterior posterior pituitary. Different hormones are secreted in different areas of the anterior pituitary. - central "mucoid" wedge contains basophils - lateral wedge contains acidophils - note also: dispersed chromophobe cells Note also: pars intermedia (of anterior pituitary) which consists of small cystic structures lined by a cuboidal epithelium, known as Rathke's pouch remnants. Anterior vs posterior pituitary ![[Pasted image 20231001135111.png]] ![[Pasted image 20231001135142.png]] The anterior is glandular, larger and darker staining, as it largely contains epithelial cells. The posterior is smaller, stains lighter as it mainly consists of largely unmyelinated axons. The posterior pituitary is contiguous with the infundibulum or 'stalk'. Hormones secreted by the anterior pituitary: GH, PRL, ACTH, TRH, FSH and LSH. Hormones secreted by the posterior pituitary: ADH and oxytocin. Anterior pituitary cell types There are three cell types of the anterior pituitary. They appear differently on H and E staining due to their differing affinities, and are named thusly: - Acidophils: appear pink and secrete GH and PRL - Basophils: appear purple and secrete ACTH, TRH, FSH and LH - Chromophobes: stain pale, and contain few cytoplasmic granules. May also contain resting cells, or degranulated cells. ![[Pasted image 20231001135659.png]] Note that individual hormone secreting cells cannot be distinguished by typical H&E staining, Instead specific cell types are identified by immunohistochemical staining. ![[Pasted image 20231001140150.png]] Secretory granules can be identified on EM ![[Pasted image 20231001140218.png]]. ![[Pasted image 20231001140658.png]] Note also that the distribution of cell types in the anterior pituitary is not even: - somatotrophs comprise 50% - lactotrophs: 15-20% - corticotrophs: 15-20% - gonadotrophs: 10% - thyrotrophs: 5% ![[Pasted image 20231001140333.png]] Posterior pituitary The posterior is smaller, stains lighter as it mainly consists of largely unmyelinated axons. The posterior pituitary is contiguous with the infundibulum or 'stalk'. The non-myelinated axons arise from neurosecretory cells located in the hypothalamus containing ADH and oxytocin. They appear as pink and fluffy, with no nuclei ^[cell bodies up in hypothalamus]. It also contains pituicytes, seen as nuclei. They serve as the glial cells of the posterior pituitary and support neuronal cells. Pars tuberalis and pars intermedia The pars tuberalis surrounds the infundibulum and mainly consist of gonadotrophs. The pars intermedia is rudimentary in humans and is made up of colloid-containing follicles. It releases MSH. Pituitary disease Pituitary adenomas are a common disease of the gland. Histological sections appear more homogenous, as all cells have arisen from the same progenitor. Chromatin has a "salt and pepper" appearance. It is also has a granular appearance due to the presence of secretory granules.

Answer 16

Location Adrenal glands are found near the upper pole of the kidney. Macroscopy Adrenal glands are small and flat. Each weighs 5g on average. 50-30 x 10 mm. The adrenal gland contains two embryological and functionally different types of endocrine tissue. Microscopy The adrenal gland is composed of several layers. - capsule: outermost layer, comprised of connective tissue - cortex, itself comprised of three zones: - zona glomerulosa, 'like glomeruli' - zona fasiculata, 'bundles' - zona reticulatis, 'net' - medulla: innermost layer, - Cortex has lipid appearance on H&E because the cortex produces cholesterol-derived hormones - zona glomerulosa contains ovoid clusters of cells, appears like glomerulus. Secretes aldosterone, or mineralocorticoids -- so named for their effect on the effect on mineral e.g. Na metabolism - zona fasciculata contains cells in bundles or rows i.e. radially arranged. It is rich in lipid droplets. Zona fasciculata secretes cortisol - zona reticularis have an irregular arrangement of cords of cells, "net-like". Cells contain a lipid structure called lipofuschin. RBCs within capillaries can be seen i.e. has a prominent capillary network. Secretes androgens and glucocorticoids -- so named for their effect of raising blood glucose. - Medulla is comprised of chromaffin cells - These are catecholamine containing granules which are oxidised to brown colour by chrome salts - They have large nuclei with basophilic granular cytoplasm (i.e. containing hormones) - cytoplasm does not contain lipid - Secretes adrenaline and noradrenaline - Tissue is also rich with RBCs in capillaries Function - Cortex - Zona glomerulosa = secretes aldosterone - Zona fasciculata = secretes cortisol - Zona reticularis = secretes androgens and glucocorticoids - Medulla = secretes epinephrine, norepinephrine Diseases - adrenocortical hyperplasia - adrenocortical carcinoma - benign and malignant phaeochromocytomas ![[Pasted image 20231001144707.png]]

Answer 17

Uterus - endometrium comprised of glands and stroma - myometrium: smooth muscle, lined by endometrium - Endometrium: tubular glands lined by simple columnar epithelium - Endometrial stroma: small sesame seed-like specialised fibroblasts closely packed - Endometriosis: endometrium outside the uterus (can occur anywhere) - Adenomyosis: endometrium within myometrium - Look similar microscopically, but are distinct diseases with different prognoses - thickened uterine wall because smooth muscle hypertrophies - Deposits look like endometrium - have glands with stroma and signs of haemorrhage - Complications: chronic pain (bleed on cyclical basis causing inflammation and pain), infertility --- Fallopian Tube - Muscular (Smooth) tube connecting the ovary with the uterus. * Tubular structure with smooth muscle coat * Ciliated columnar cells: motilit * Non-ciliated columnar cells with apical granules: secrete fluid - Intercalated/Peg cells: non-ciliated, may act as stem cells * Distal parts have fimbriae (finger-like projections that catch egg in ovulation) * Centre of tube has plicae (complicated folds) - large SA to grab egg and move along the tube * Movement along the tube due to smooth muscle peristalsis and cilia ![[Pasted image 20231001161418.png]] Problems that can occur in the fallopian tube include: - infection or inflammation known as salpingitis - acute, chronic, granulomatous, foreign body type - obstructive causes: mainly ectopic pregnancy, endometriosis, paratubal cyst ^[common but if >5cm can cause torsion (present with pain, nausea and vomiting)] - benign tumour: adenomatoid - malignant neoplasm: primary carcinoma, typically from columnar epithelial lining or secondary metastasis from ovary or other abdominal organs. Greater risk with BRCA mutation Endometrial Carcinoma - Endometrial carcinoma - Complex glandular and papillary architecture - Glands arranged back-to-back without intervening normal stroma - Oestrogen-driven disease ∴ cases increasing with obesity (more aromatisation in peripheral fat = ↑ oestrogen levels) and may improve after menopause when oestrogen is driven down - Glands and papillae are lined by multiple layers of cells - Cells show large nuclei with nucleoli, altered nuclear/cytoplasmic ratio and pleomorphism - Malignant glands start to invade myometrium - Presentation: PV bleeding intermenstrual, heavy, prolonged or post-menopausal ![[Pasted image 20231001161942.png]] Leiomyoma #### H&E: Leiomyoma x100 - Smooth muscle proliferation, homogenous whorled appearance. - Complications: Pain, Menorrhagia, Infertility, Compressive symptoms. ![[Pasted image 20231001161959.png]] - Leiomyoma: smooth muscle proliferation (fibroids) - Microscopy: homogenous, whorled appearance, fascicles of smooth muscle, circumscribed, abundant pink cytoplasm and spindled nuclei - Complications: pain (if large/heavy or necrotising), menorrhagia and dysmenorrhoea (uterus so large causing increased endometrial surface area ∴ heavy bleeding), infertility or pregnancy loss as leimyomas interfere with implantation, compressive symptoms Fallopian Tube - Salpingitis Aetiology: Infection - STI (Neisseria gonorrheae, Chlamydia, Mycoplasma). - Post instrumentation / IUD / post-pregnancy or abortion. #### Macro - Adhesion and fusion of fimbria. - Dilated tube. - Filled with pus. - Often asymptomatic or very mild symptoms e.g. low-grade abdominal pain #### Micro - Acute (neutrophils) or chronic inflammation (plasma cells). - Plicae fused. #### Complications - Abscess formation. - Ectopic pregnancy. - Infertility - Systemic sepsis and death ![Salpingitis Image](http://library.med.utah.edu/WebPath/webpath.html) ![[Pasted image 20231001161559.png]] Fallopian Tube - Ectopic Pregnancy Aetiology - Chronic salpingitis: Inflammation fuses the plicae and can, therefore, trap the ovum. - Congenital abnormalities. - Functional tubal disturbances. - Endometriosis. Macro - Dilated. - Hemorrhagic. - +/- fetus. Micro - Chorionic villi. Treatment - Salpingectomy - with implications for ferility **Appearance**: - Fallopian tubes are distended with ruptured wall exuding hemorrhagic material and fetal tissue. ---

Answer 18

Timeline of development - at 5 weeks, primordial germ cells migrate from yolk sacs to the urogenital ridges -- these will eventually form the gametes - between 5-7 weeks the kidneys start to ascend - at two months is the indifferent stage - between 10-12 weeks the 'switch' begins: formation of seminiferous tubules and ovarian follicles ^[gonad formation guides tube formation] - 3 months - external genitalia develop - Between 8-9 months: testes descend into the scrotum ^[ovaries also descend but do not cover the same distance, end up in pelvis] Recall that by **three** weeks, the **tri**laminar germ disc has formed. This consists of ectoderm, mesoderm and endoderm. The urogenital system is derived from intermediate mesoderm. The intermediate mesoderm migrates to form a ridge near or lateral to the hindgut. This forms the urogenital ridge -- the beginnings of the urogenital system. ndifferentiated stage Key notes about the undifferentiated stage are listed below: - germ cells from yolk sac migrate into the intermediate mesoderm - note that there are two connections from the embryo to yolk sac, one is the allantois: which is responsible for waste storage - note also the cloacal membrane, just over the cloaca, which becomes the urethral and rectal openings - Note the two ridges that form from the intermediate mesoderm: nephrogenic and genital ridges - note also the mesonephric and paramesopheric ducts - mesonephric duct and tubule formed from teh condensation of germ cells - this forms a primitive kidney, the mesonephros, the first functioning kidney ^[although second incarnation] and associated mesonephric ducts. Both are functional - note the mesonephros is composed of glomerulus, Bowman's capsule and mesonephric tubule -- glomerulus comes from branches of dorsal aorta which is positioned medial to the mesonephros (R and L) - mesonephric tubules connect to mesonephric duct - paramesonephric duct forms from invagination of visceral peritoneum - note also cloaca separates in urogenital sinus - source of paramesonephric and mesonephric ducts drainage - genital ridge - site of gonad formation. Mesonephric tubule located between duct and gonad All this occurs between week 5 and 6

Answer 19

- Mesonephric (Wolffian) ducts: seminal vesicle, vas deferens, epididdymis - Mesonephric tubules: efferent ductules (Connecting rete testis to epididdymis) - Medullary/testis cords: seminiferous tubules abd rete testis - Paramesonephric (Mullerian) ducts: Fallopian tubes, uterus and upper vagina - Cortical cords: ovarian follicles - Genital tubercle: glans penis and glans clitoris - Lateral tubercle: body of penis and clitoris - urethral fold: penile urethra and labia minora - labioscrotal swelling: scrotum and labia majora

Answer 20

Gestational Diabetes Mellitus (GDM) - Glucose intolerance with onset or first recognition in pregnancy (ADA) - Carbohydrate intolerance of varying severity which is diagnosed in pregnancy and may or may not resolve after pregnancy (ADIPS, IDF) - Pregnancy makes insulin resistance worse, so ß cells have to work harder - Treatment of GDM can improve adverse outcomes - Birth weight, LGA, macrosomia, pre-eclapmsia, SGA, NICU admissions, etc. - Risk of developing T2D is 10x higher in GDM compared to normal - Offspring of GDM mothers have a higher prevalence of T2D/pre- diabetes and of metabolic syndrome OGTT at 24-28 weeks - If early screen normal for the high-risk group - All other women (excluding known pre-existing diabetes) GDM Diagnosis GDM diagnosed on OGTT if: - Fasting BGL ≥ 5.1 mmol/L - 1h BGL ≥ 10.0 mmol/L - 2h BGL ≥ 8.5 mmol/L - This is different from OGTT cut-offs for diabetes outside of pregnancy Impacts on foetus: * Plethoric - high Hb * ↑ adiposity because high glucose from mother crosses placenta and feeds baby too much - makes lots of fat * Baby’s lungs mature slowly - often sluggish * W/o glucose from mother, glucose can crash post-birth * Higher rates of perinatal mortality * Higher rates of congenital malformation (T2D worse outcomes than T1D ## Footnote * High risk patients * Asian, Indian, Aboriginal, Torres Strait islander, Pacific Islander, Maori, Middle Eastern, non-white African * Previous GDM * Previously elevated blood glucose level * Maternal age ≥ 40 years * Family history DM (1st degree relative with DM or sister with GDM) * BMI > 35kg/m2 * Previous macrosomia (baby with birthweight > 4500g or > 90th percentile) * PCOS * Medications: corticosteroids, antipsychotics

Answer 21

Prolactin - Secreted by lactotrophs of anterior pituitary - Lactation: only known function - Inhibits reproductive hormone secretion - **Release inhibited by dopamine ("prolactin inhibitory factor") - no stimulating factor - In animals, it plays a role in osmoregulation and growth - Stalk transection leads to an increase in prolactin levels - Pituitary tumors can lead to mass effects, as they enlarge upwards - Common mass effect symptoms include: - Absent headache - Impingement on the optic chiasm, resulting in bitemporal hemianopia - Cranial nerve effects - Hydrocephalus - Hypopituitarism - Mild hyperprolactinemia due to stalk compression or disruption ^[no pain fibres, can go unnoticed] ^[stalk compression, interrupts dopamine, high PRL] - Diabetes insipidus (when the tumor is suprasellar) ^[hypothalamus and pituitary damage, poor ADH, thirst and urination] Prolactinomas are very common. - low levels of other pituitary hormones, such as thyroid hormones and cortisol What are the symptoms of having a prolactinoma? Among women, common symptoms of having a prolactinoma include: - changes in menstruation NIH external link, such as irregular periods or no periods - infertility - milky discharge from the breasts, also called galactorrhea - loss of interest in sex - pain or discomfort during sex due to vaginal dryness NIH external link Among men, common symptoms include: - loss of interest in sex associated with low levels of testosterone - erectile dysfunction

Answer 22

- UTI - Gastro - ectopic pregnancy - appendicitis

Answer 23

- A chain: 21 AAs - B chain: 30 AAs - 2 disulphide bonds link A&B chains - C-peptide (produced 1:1 ratio with mature insulin) - Islet beta cell * Produced by ß cells in membrane-bound granules * Synthesised as pre-proinsulin → cleaved to pro-insulin (A and B chains disulphide linked) * Pro-insulin → mature insulin + C-peptide * C-peptide produced in 1:1 ratio with mature insulin - measured to indicate endogenous insulin production * Many ER required for protein synthesis * Many mitochondria - high energy use cell 1. Glucose uptake via GLUT2 channels 2. Glucose metabolism 3. Increase ATP/ADP ratio 4. Closure of ATP-sensitive K+ channels 5. Depolarisation of plasma membrane 6. Opening of voltage-dependent Ca++ channels 7. Influx Ca++ 8. Ca++ induced insulin vesicle exocytosis

Answer 24

Types of Tolerance - Central tolerance: - Deletion - Editing - **Site of Action** - Thymus - Bone marrow - Antigen segregation - Physical barrier to self-antigen access to lymphoid system - Site of action: Peripheral organs (e.g., thyroid, pancreas) - Peripheral anergy - Cellular inactivation by weak signaling without co-stimulus - Secondary lymphoid organ - Regulatory T cells - Suppression by cytokines, intercellular signals - Secondary lymphoid tissue and sites of inflammation - Functional deviation - Differentiation of regulatory T cells that limit inflammatory cytokine secretion - Secondary lymphoid tissue and sites of inflammation - Activation- induced cell death - apoptosis - secondary lymphoid tissue and sites of inflammation

Answer 25

- Breakdown in tolerance - Ability to distinguish between ‘self’ and ‘non-self’ - Central: thymus and bone marrow - Peripheral - Specific adaptive response against self antigens - Impossible to eliminate the antigen completely - Sustained immune response - Chronic inflammation involving target tissues - **Factors influencing susceptibility to autoimmune disease** - Genetic factors - Familial clusters, HLA association - Sex - Age - Environmental factors - Ultraviolet radiation, drugs, viruses, chronic infection, gliadin - Loss of regulatory T cells - **Susceptibility to autoimmune disease** - Familial Clusters: suggestive of a more generalised heritable defect as seen in: - Type I diabetes mellitus - Graves’ disease, Hashimoto’s thyroiditis, autoimmune gastritis, hypoadrenalism, vitiligo - Systemic lupus erythematosus scleroderma - Autoimmune polyendocrinopathy syndromes - HLA associations - with specific HLA complexes are associated with incidence of autoimmune diseases, such as: - HLA B27 - Ankylosing spondylitis - Anterior uveitis - Reactive arthritis - HLA DR3 - Graves’ disease - Myasthenia gravis - Systemic lupus erythematosus - HLA DR4 - Diabetes mellitus - Rheumatoid arthritis - Pemphigus vulgaris ![[Pasted image 20231018130754.png]] **Other factors that influence susceptibility to development to autoimmune disease** - Sex - More common in female patients, particularly those of childbearing age - Age - Environmental exposures - UV radiation - Drugs - alpha methyldopa - Certain viral and chronic infections - Chronic inflammation leads to greater chance of exposure to self antigens - Gliadin - Loss of regulatory T cells - May be secondary to other medical conditions and exposures, or perhaps idiopathic.

Answer 26

**CTLA-4** - site of action: secondary lymphoid organs - induction or priming is **inhibited** - CD4+ is more than or same as CD8+ - leads to cellular expression of Tregs and activated T cells - binds to B7 with high affinity and removing B7 from APCs by competitively inhibiting CD28 - A role of Treg mediated suppression of immune responses **PD-1** - site of action: peripheral tissues - effector phase is **inhibited** - CD8+ more than CD4+ - leads to cellular expression of activated T cells - Signalling inhibitor of CD28 and TCR, inhibiting kinase-depending signals by activating phosphatase - NOT involved in Treg-mediated suppression of immune responses

Answer 27

**From week 4: mesonephros and mesonephric ducts form** **During weeks 5 and 6, indifferent gonads form, with primordial germ cells from yolk sac, epithelial cells and mesenchymal cells** **SRY gene turned on from week 7 resulting in TDF expression and testes development** **Medullary (testis) cord contains primitive germ cells develops in response to TDF, Sertoli (sustentacular cells) and Leydig or interstitial cells** - In males, most of action occurs in the medulla in the gonads - Testicular cords developing from mesonephric tubule, branching further into seminiferous tubules - Developing tunica albuginea - Rete testis, efferent tubules and mesonephric ducts develop - from mesonephric duct: epididymis, vas deferens, ejaculatory duct and seminal vesicles develop ^[seminal vesicles an outgrowth] - Paramesonephric or Mullerian duct degenerates **Leydig cells derived from mesenchyme produce testosterone, resulting in development of male genital ducts, male external genitalia and accessory glands** - Interstitial or Leydig cells secrete testosterone, responsible for male development and maintenance of libido, outside the seminiferous tubules - mesonephric duct develops into epididymis, vas deferens, ejaculatory duct and seminal vesicle - mesonephric tubules develop into efferent ductules - urogenital sinus develops into prostate and bulbourethral glands **Sertoli cells produce AMH resulting in paramesonephric duct degeneration** - Sertoli cells, within the seminiferous tubules, provide support to spermatogenic cells and secrete AMH ![[Pasted image 20231010165904.png]] ![[Pasted image 20231010170304.png]] ## Testes descent The testes and ovaries descends during the 8th and 9th months. The gubernaculum guides the testes or ovaries down. It moves anteriorly through the layers of the abdomen wall. Invagination of parietal peritoneum assists testes and makes space. This is why layers of the scrotum are continuous with the abdominal wall. - transversalis fascia becomes the internal fascia of the scrotum - internal oblique becomes cremaster muscle - external oblique fascia becomes external fascia A problem that occurs is undescended testes - high scrotal or higher in the inguinal canal or abdomen. Another problem that can occur is hydrocele if invagination is not completely closed- can be non- or completely communicating hydrocele ^[recall direct or indirect hernias -- via the abdominal wall or via the inguinal canal, see [[Anatomy Lecture 5]]]

Answer 28

**During week 4 the mesonephros and mesonephric ducts develop** **Indifferent gonads, with migration of primordial germ cells from yolk sac and formation of Mullerian ducts** (persistence of paramesonephric ducts) Cells of ovary expand **from cortex**. Primitive sex cords develop into cortical cords and ovarian follicles, containing oocytes and follicular cells. **From week 7 and onwards, SRY gene not present, therefore no TDF and development of ovaries** In the absence of a Y chromosome female development occurs. Mesonephric tubule and duct i.e. Wolffian ducts degenerate. **Development of ovaries: primary cells include oocytes (primitive germ cells), and follicular cells which produce estrogen, stimulating the formation of female genitalia** ![[Pasted image 20231010171412.png]] **A lack of testes means no testosterone or AMH, therefore uterine tubes, uterus and vagina develops** The paramesonephric ducts are progenitors of the upper female GT. The two ducts come together and fuse to form the uterus and upper part of the vagina (at the caudal end). Unfused portions (at the cranial end) form the uterine tubes. Ovaries descend slightly. The ovaries stay in the pelvis. The gubernaculum also guides this process. Remnants of the descent of the ovaries persist as the ovarian ligament (attaches to lateral uterus) and round ligament (attaches uterus to labia majora) (see also [[Anatomy B3 - Lecture 1]]

Answer 29

Male - hypospadia: orifice not fully closed during weeks 10 and 12 in males - phimosis and paraphimosis: - Phimosis is a condition _in which the foreskin is tightly stretched around the head of the penis and cannot be_ pulled back freely i.e. unable to be retracted. - Paraphimosis occurs when retracted foreskin cannot be pulled back to cover the glans penis (i.e. entrapment in the retracted position) - 5-a-reductase deficiency - Guevedoces - develop male genitalia around 12 due to surge in testerone during puberty - leads to development of penis - Research into condition resulting in development of finasteride (enlarged prostate and male pattern baldness) Female - 46 XX CAH - Comprises a group of inherited disorders relating to the adrenal glands, characterised by deficiency in an enzyme for formation of cortisol and aldosterone and subsequent overproduction of androgen - Causes clitoral enlargement and labial fusion

Answer 30

Cervix Three main parts: - endocervix - squamocolumnar junction: transformation zone of squamous to columnar - site where CST taken from - ectocervix ![[Pasted image 20231001162057.png]] **Cervix - Infection - Trichomonas. - Candida. - HPV. **Cervix - Benign Neoplasm - Polyps. **Cervix - Malignant Neoplasm - Squamous cell carcinoma. - Adenocarcinoma. ![Cervix Pathology Image](http://library.med.utah.edu/WebPath/webpath.html) Vagina ![[Pasted image 20231001162133.png]] - Fibromuscular canal. - Mucosal layer – squamous epithelium. - Lamina propria – elastic fibers. - Smooth muscle with rugae - Adventitial layer. ![[Pasted image 20231001162143.png]] Vagina - Pathology - **Congenital** - Atresia, septate vagina, Gartner duct cysts. - **Infection** - Candida, HPV. - **Benign Neoplasm** - Squamous papilloma. - **Malignant Neoplasm** - Squamous cell carcinoma, Clear cell carcinoma, Embryonal rhabdomyosarcoma. - Vaginal pathology except for infection is rare. Vulva ![[Pasted image 20231001162212.png]] - normal vulva has stratified non-keratinising squamous epithelium - highly vascularised beneath epithelium due to erectile tissue Vulva - Pathology - **Congenital** - Ectopic mammary tissue. - **Inflammation** - Dermatitis, lichen sclerosus, lichen planus. - **Infection** - HPV, candida. - **Benign Neoplasm** - Fibroepithelial polyp, nevi, hidradenoma papilliferum. - **Malignant Neoplasm** - VIN/Squamous carcinoma, melanoma, Paget’s disease. **Vulva - Leukoplakia - Thickened layer of keratin on the mucosal surface (hyperkeratosis). - Clinical Diagnosis: White plaque-like thickening of the mucosa. - **Benign** - Lichen sclerosus. - **Malignant** - Early squamous cell carcinoma. - Needs a biopsy. Vulva - Lichen Sclerosus (int) - Postmenopausal women. - Pathogenesis: autoimmune, genetic, or hormonal. #### Macro - An area of leukoplakia. #### Micro - Hyperkeratosis, thinning of the epidermis, loss of rete pegs, dermal collagen altered. - Not in itself a premalignant condition but is associated with an increased risk of squamous cell carcinoma. Vulval Intraepithelial Neoplasia (int) - Squamous epithelial neoplasia without invasion beyond the basement membrane (pre-invasive). - **Risk factors**: HPV, cigarette smoking, lichen sclerosis. #### Macro - Leukoplakia. #### Micro - Hyperkeratosis, thick epithelium (acanthosis), elongation of rete pegs, nuclear atypia, mitoses. ![[Pasted image 20231001162332.png]] ## Vulval Squamous Cell Carcinoma - **Age**: >60, rare in women younger than 30. - **Risk factors**: HPV, cigarette smoking, immunodeficiency. - **Site**: Labia majora, also labia minora, clitoris. - **Prognosis**: 5-year survival 50-75%. ![[Pasted image 20231001162405.png]]

Answer 31

Urothelial Neoplasms ![[Pasted image 20231001160336.png]] Urothelial neoplasms can be flat or papillary: - flat: benign (regenerative changes after inflammation) and malignant (CIS and invasive urothelial carcinoma) Or papillary: #### Benign - Papilloma #### Malignant - Papillary Urothelial Carcinoma (may be non-invasive or invasive) Papillary Urothelial Neoplasm of Low Malignant Potential Flat Urothelial Malignancy Urothelial Carcinoma in Situ - Presentation: Asymptomatic or symptoms of urinary tract infection not responding to treatment. - Cystoscopy: Flat red inflamed-looking mucosa. - Histology: Features of malignancy (NC ratio, hyperchromasia, mitotic activity etc): full thickness, urothelium replaced by large pleomorphic atypical cells. No breach in the basement membrane. Haemorrhagic change to urothelium. - Macroscopy: haemorrhagic, multifocal flat lesions Note: - it may be a diffuse process involving the entire bladder - important to rule out invasive areas, and any associated papillary lesions Some risk factors include: - genetic: HNPCC: inherited genetic mutations in mismatch repair genes-- tend to get colon carcinoma but can get different malignancies in other parts of body - acquired: smoking Treatment: - BCG - placed in bladder: causes chronic hypersensitivity inflammatory reaction so entire urothelium becomes inflamed, drops off, dies and falls out ![[Pasted image 20231001160545.png]] Urothelial Carcinoma - Invasive carcinoma - High grade: invasion muscularis propria, low prognosis - Low grade: invasion into lamina propria - surface epithelium contains malignant cells that have invaded past BM, which them forms a tumour seen macroscopically by cystoscopy - Treatment: cystoscopy and replacement with neo-bladder made of ileum ![[Pasted image 20231001160800.png]] Why do we need to differentiate between the levels of invasion? - Different Treatments - Urothelial Carcinoma in situ: Transurethral resection & intravesical BCG AND Tumor invading through the muscularis propria: Cystectomy ~ Papillary neoplasms~ #### Papillary Architecture It is present in normal tissues e.g. choroid plexus as well as several tumours. - Architectural Pattern: Finger-like projection - can be seen with cystoscopy: may hypertrophy if bladder chronically obstructed by multiple papillae - Covering epithelium. - Microscopy: Core of blood vessels and connective tissue in the center i.e. fibrovascular core. - Presentation: - Delicate papillae break due to stresses leading to bleeding from the central core of blood vessels. - This leads to patients present with microscopic or macroscopic hematuria. - **Hematuria outside of the setting of a UTI is abnormal and must be investigated ![[Pasted image 20231001161030.png]] ![[Pasted image 20231001161057.png]] Benign * Papilloma * Lined by essentially normal urothelium * Normal thickness * Orderly and organised architecture * No mitoses Malignant * Papillary urothelial neoplasm of low malignant potential * Lined by cytologically troublesome urotheliu * Increased thickness of urothelium Mild disarray * Occasional mitoses * Papillary urothelial carcinoma (may be non-invasive or invasive) * Lined by cytologically malignant urothelium * Very increased thickness of urothelium * Complete loss of organisation * Several mitoses Cystoscopic Appearance - Fronds like a sea anemone, floating in the urine. #### Macroscopic Appearance - Finger-like papillary projections. Cytological Classification (Grade) - The nuclear appearance gives the grade. - Low grade - Non-invasive - Cells are bland. - High grade - Invasive - Cells are very pleomorphic and large. Invasion (Stage) - The depth of invasion gives the stage. - Muscularis propria invasion is a poor prognosis. - Low grade - Non-invasive - The cells are limited to the urothelium, and there has been no breach of the basement membrane. - Invasive - The cells have invaded beyond the basement membrane into the submucosa and muscle.

Answer 32

Prostate Gland: Neoplastic Lesions * Neoplastic lesions - Epithelial (glands) - Benign: adenosine - Malignant: acinar adenocarcinoma - Mesenchymal (stroma) - Benign: leiomyoma - Malignant: Leiomyosarcoma and Stromal sarcoma - Mixed epithelial and mesenchymal - Benign: Benign Prostatic Hyperplasia (BAH) - Malignant: Epithelial stromal sarcoma AND Invasion from nearby organs: bladder, urethra, rectum - **Benign Prostatic Hyperplasia (BPH)** **Presentation** * Lower urinary tract symptoms (LUTS) due to voiding difficulties * Haematuria * Recurrent UTI * Bladder calculi * Acute urinary retention * Urinary tract obstruction ± renal failure **Risk factors** * Acquired * Age (50% by 60, 90% by 85) * Obesity/metabolic syndrome * Sedentary lifestyle * Diet * Protective: Moderate ETOH consumption, citrus juice, lycopene, carotenoids, vitamin A * Risk increases: coffee, vitamin C supplements * Genetic * Ethnicity (African descent = worse disease at younger age) * Poorly understood genetic factors, but familial clustering seen **Pathophysiology** * Very common affecting most older men (80% of men 70+) * Increase in prostate size due to hyperplasia of glandular and stormy tissue * Testosterone and DHT-driven disease * 5α reductase (released by stromal cells) converts testosterone to potent DHT (x10 potency) * Prostate enlargement contributes to urinary dysfunction * Obstructive urinary symptoms * Progressive urodynamic dysfunction with alterations in smooth muscle tone **Macroscopy** * Enlarged prostate * Hyperplastic nodules of varying sizes * Distortion/compression/elongation of prostatic urethra due to nodules **Microscopy** * Nodular transformation of prostatic parenchyma * Nodules composed of: * Increased numbers of glandular structures (bilayer: inner liminal and outer basal layer) * Expanded fibromuscular stroma with fine vascularity * Glands still lined by 2 layers of cells (epithelial and basal) **IHC** * Antibodies targeted towards basal cells (high molecular weight cytokeratins) - all glands surrounded by immunostain **Complications** * Progressive symptoms, recurrence after surgery common * Acute urinary retention * Renal failure (complete obstruction: acute or chronic) * Recurrent UTI * Bladder complications (stones, diverticuli) **Treatments** * Medical * Androgen antagonists (e.g. 5HT inhibitors), smooth muscle relaxants (α blockers) * Surgical * TURP (transurethral resection of prostate to release urethral obstruction) * Prostatectomy (Millin procedure) ![[Pasted image 20231001165644.png]] - **Histology of BPH** Microscopy * Nodular transformation of prostatic parenchyma * Nodules composed of: * Increased numbers of glandular structures (bilayer: inner liminal and outer basal layer) * Expanded fibromuscular stroma with fine vascularity * Glands still lined by 2 layers of cells (epithelial and basal) ![[Pasted image 20231001165613.png]] - hyperplasia of glands and stroma - glands still lined by two layers of cells - cells are bland looking - **Radical Prostactomy** shows carcinoma of prostate, yellowish nodeules - **Prostatic Adenocarcinoma** - Elderly males - May or may not present with symptoms - Serum levels of Prostate Specific Antigen (PSA) may rise Diagnosis: Digital Rectal Examination and Ultrasonography help in diagnosis - Prostate Biopsy is needed for confirmation Treatment options: Radical prostatectomy or Radiotherapy or Hormone-specific therapy - Histology: - *Cells show prominent nucleoli* - *Complete absence of basal cells - back to back glands i.e. cribriform pattern IHC: - confirms absence of basal cells and suggests spread Gleason Grading (architecture only) * 1: Small, uniform, evenly-spaced glands * 2: Glands slightly irregular with more intervening stroma * 3: Irregular and irregularly-spaced glands * 4: Gland fusion * 5: No glands - solid nests, single cells, necrosis

Answer 33

Testis: Non-neoplastic lesions ### Cryptorchidism - *Undescended testes* - *Shows atrophy and loss of normal seminiferous tubulues: hyalinsation around them appears pink* - absent Leydig cells in stroma - *Increase risk for malignancy* Torsion - *Occurs post-trauma or in undescended testis* - *Very painful (emergency)* - *Venous type infarction* - *Orchidopexy* CLASSIFICATION TESTICULAR GERM CELL TUMOURS - SEMINOMA - radiosensitive - Due to spermatocytic differentiation - *Typical/Anaplastic* - *Spermatocytic* Non-seminomatous - radioresistant: Spread is early and via bloodstream, especially to lung Tumours have trophoblastic, yolk sac and undifferentiated elements, have worse prognosis - *Intraembryonic differentiation* - teratoma: mature and immature - *Extraembryonic differentiation*: yolk sac or choriocarcinoma - *Undifferentiated tumors*: embryonal carcinoama All of the above are mixed germ cell tumours. ![[Pasted image 20231001170210.png]] - **Seminoma** - *Most common-50%. Usually 20 – 40 years old* - *Painless, unilateral, bulky, testicular enlargement* - *Gross appearance: Homogeneous, creamy white tumor, usually no hemorrhage or necrosis* - ![[Pasted image 20231001170228.png]] - *Cells show prominent nucleoli* - *Complete absence of the basal layer ![[Pasted image 20231001170240.png]] Histology: - Sheets of tightly packed cells with dark, central nuclei, prominent nucleolus, and clear cytoplasm - Characteristic lymphoid infiltrate - 50% or so of seminomas that contain syncytiotrophoblast (produced HCG) - Spread via lymph nodes NON-SEMINOMATOUS GERM CELL TUMOURS (NSGCT) - **Teratoma** - **Embryonal Carcinoma** - **Yolk Sac Tumour** - **Choriocarcinoma** - Unlike seminoma, spread is early and via the bloodstream, especially to the lung - Tumors containing trophoblastic, yolk sac, and undifferentiated elements have the worst prognosis Teratoma - **Mature Teratomas** - Usually seen in young children and have all three embryonic layers (skin, hair, cartilage, bone) which are well-differentiated, benign, and haphazardly arranged - **Immature Teratomas** - As above but primitive cells and haphazardly arranged - May have foci of non-germ cell tumors (e.g., squamous cell cancer) - 45% are mixed with other types of germ cell tumors - Heterogeneous helter-skelter collection of various types of tissues - Malignant in post-pubertal males Embryonal Carcinoma - Cut surface of the testis, which is completely replaced by hemorrhagic tumor nodules - 20-30 years age group - macroscopy: Variegated appearance with fleshy and cystic or necrotic areas - microscopy: Sheets of immature, pleomorphic cells in solid, tubular, or papillary patterns with many mitoses and tumor giant cells - H+E: Embryonal carcinoma of the testis x 200 (note pleomorphic cells arranged in glandular formations)![[Pasted image 20231001170311.png]] Yolk Sac Tumour - H+E: Yolk sac tumour of the testis x 200 (note cells are arranged in reticular (net-like) patterns with little holes (microcystic)): - Most common testicular tumor in <3yr olds - In adults, usually in combination with other types - Characteristic histological appearance forming solid, papillary, and microcystic patterns - Secrete ALPHA FETOPROTEIN (AFP): can be identified in serum Choriocarcinoma - Composed of trophoblastic tissue: cytotrophoblast and syncytiotrophoblast: Multinucleated giant cells detectable - Highly malignant, haeemorrhagic, very purple cytoplasm (syncytioblast origin) - Generally occur along with other germ cell tumors - Secrete HUMAN CHORIONIC GONADOTROPIN (HCG). Can detect in serum and by immunohistochemistry \ ![[Pasted image 20231001170338.png]] note mononuclear cytotrophoblast (one nucleus) with multinucleated syncytiotrophoblast: note abundant hemorrhage with RBCs typical of these tumors Mixed Tumours - EMBRYONAL CARCINOMA + TERATOMA - 60% of germ cell tumors have more than one type of germ cell tumor patterns - Usually more aggressive - Common mixtures - Teratoma/embryonal/yolk sac and Seminoma/embryonal carcinoma Tumour Markers in Testicular Tumour - AFP, HCG, LDH measured before and after orchidectomy - HCG elevated in Trophoblastic tumors and some Seminomas - AFP elevated in Yolk sac tumors - AFP or HCG or BOTH increased in 50% of teratoma & 90% of teratoma+embryonal cancer - Useful for Staging, Monitoring response, Assessing tumor burden (LDH)

Answer 34

Malformation: morphological defect of an organ or larger region of body resulting from an intrinsically abnormal developmental process e.g. absence of thumb due to abnormality of apical ectodermal ridge that controls limb bud development Dysplasia: abnormal organization of cells into tissue (dyshistogenesis) and its morphological result e.g. Marfans syndrome Disruption: morphological defect of an organ, part of an organ or a larger region of body resulting from an extrinsic breakdown of, or an interference with, an originally normal process e.g. amniotic band wraps around developing limb producing distal amputation Deformation: abnormal form, shape or position of a part of body caused by mechanical forces e.g. club foot Anomaly: deviation from expected or average type in structure, form and/or function which is interpreted as abnormal e.g. single palmar crease Sequence: cascade of primary and secondary events that are conseuqneces of a single primary malformation or disruption e.g. X-linked spina bifida/myelomeningocele sequence Syndrome: multiple anomalies thought to be pathogenically related and not representing a sequence e.g. Down syndrome Association: any non random occurrence in one or more individuals of severe morphologic defects not identified as a sequence or syndrome - VATER associations are Vertebral, Anorectal, Tracheo-oesophageal, Radial and Renal defects and involve mesodermal derivatives

Answer 35

Risk factors 1 - Multiple sexual partners 2 – Young age at first intercourse 3 – High parity 4 – Persistent infection of high oncogenic risk HPV 5 – Immunosuppression 6 – Certain HLA subtypes 7 – Use of OCP 8 – Use of nicotine HPV DNA integrates into host squamous epithelial genome HPV infects immature basal cells of squamous epithelium in areas of epithelial breaks or immature metaplasia present at squamo-columnar junction HPV replicates in mature non-proliferating squamous cells where they re-activate mitotic cycle Koilocyte cells appear at superficial squamous layer due to breakdown of keratin in HPV-infected cells Perinuclear halo + nuclear enlargement Function: HPV E6/E7 inactivate tumour suppressor genes (especially p53 and RB) Screening: National Cervical Screening Program Ages 25-74, every 5 years Person with a cervix Have had any type of sexual contact Pap test replaced with vaginal swab kit (self test or by clinician) Must be accessed through a doctor even if self-test (not mailed out) Self-test kit detects HPV Does not require access to cervix (vaginal swab)

Answer 36

- Endocrine organ and liver, heart-lung, and kidney dialysis machine; nutrition and immunity - The interface between mother and fetus - A diary of the pregnancy - shows the cumulative effect of pregnancy-related events Maternal spiral arteries: endometrial arteris that send blood to junctional veins Maternal veins: take deoxygenated blood away for reoxygenation Chorionic villi: foetal capillaries that dip into junctional zone to exchange nutrients, gases with maternal blood supply Infarction: tissue death of placenta due to inadequate blood supply to area Villitis: intravillous chronic inflammatory (mononuclear) cellular infiltrate chorionic villi leading to villous agglutination Changes shape with pathology: normal 500g, abnormal 1/2 trimester: cup cake, 3rd 400g and pancake, entire pregnancy 250g, pikelet Extraplacental membranes - Chorion, amnion: chroioamnionitis: acute inflammation of the membranes and chorion of the placenta Endocrine organ: Progestins Support endometrium Suppression of contractility in uterine smooth muscle Inhibits secretion of LH + FSH Estrogens Stimulate growth of myometrium and antagonize myometrial-suppressing activity of progesterone HCG Binds to LH receptor on cells of corpus luteum 🡪 prevents degeneration of corpus luteum + subsequent uterine shedding Others hPL cACTH

Answer 37

**Twin Placenta** Dividing membranes between amniotic cavities occupied by foetuses are seen between cord insertions * 2 sperm and 2 eggs = fraternal twins * 1 sperm and 1 egg that splits into 2 embryos = identical twin - **Diamnionic-dichorionic Twin Placenta (Di-Di Placenta):** or DCDA - Likelihood of dizygous twinning much more probable than monozygous twinning - **Diamnionic-monochorionic Twin Placenta (Di-Mono Placenta):** - The dividing membranes have an amnion on each surface, but no visible chorion, so this is a Monochorionic placentas imply that monozygous twinning is present MCDA: monochorionic, diamniotic (monozygotic) One house but two bedrooms MCMA: monochorionic, monoamniotic (monozygotic) One house and share one bedroom ^most risky

Answer 38

**Erection: Understanding the Neuro-Vascular Event** - when flaccid, the penis is under sympathetic control **or** adrenergic tone - sinusoids, arterioles and arterial smooth muscle is constricted - arteriolar inflow is minimal - no venous obstruction - n.b. intracavernous pressure is same as venous pressure **Tumescence: Filling of Erectile Tissue** - **Parasympathetic NS Stimulation:** - Loss of adrenergic tone leading to vascular smooth muscle relaxation. - **Vascular Changes:** - Arteriolar dilation, trabecular relaxation, sinusoids filling and expanding. = erectile tissue expansion - Compression of venules in sinusoidal space and subtunical venous plexuses obstructing outflow. - Ischiocavernosus muscle contraction squeezing crura.

Answer 39

- **Men's Changes:** - Maximum penile and testicular engorgement, increased pre-ejaculate from bulbo-urethral/Cowper's glands - Erection may vary in firmness From excitement to plateau: - full erection of penis - testes elevate towards perineum to increasing in size and becoming fully elevated - skin of scrotum tenses, thickens and elevates to scrotum thickening - colour of glans penis deepens - Cowper's gland secretion - Prostate enlarges - **Women's Changes:** - Increased blood flow to labia, vaginal expansion and elevation, elevated uterus, orgasm becomes inevitable - From the excitement to plateau phase: - uterus elevates up and away from vagina to being fully elevated - vaginal lubrication appears - inner labia swell, to increase in size and turn bright red - outer third of vagina forms orgasmic platform - clitoris enlarges and retracts under hood

Answer 40

- **Female Genitals:** - Pelvic floor: 3-8 contractions - contractions of the smooth muscle of the vagina and uterus - possible ejaculation although components not clear - urine? - peri-urethral - Bartholin's gland secretion - repeated orgasm possible - often needs direct stimulation of the clitoris, labia, and introitus rather than vaginal penetration - males and females vary in the intensity og orgasm - also characterised by skeletal muscle contraction and verbalisations - rise to peak of intensity **Emission and Ejaculation** - **Emission:** - Seminal vesicles contract rhythmically to release fluid into prostatic urethra - secretions from prostate (make the bulk of semen) - peristaltic contraction of vas deferens - small volume of fluid into ejaculatory duct Note: pre-ejaculate function not clear - pH for sperm survival - lubricate head of penis to increase pleasure - lubricate urethra to ease expulsion of semen - **Ejaculation Phase:** - Rhythmic contraction of bulbospongiosus muscle - simultaneous sphincter actions: internal sphincter closure and external sphincter open to allow expulsion of semen = sympathetic reflex - return of sympathetic control f sinusoids = constriction

Answer 41

IVF: indications * Tubal obstruction * Endometriosis * Unexplained infertility * Male factor infertility * Pre implantation genetic diagnosis (no fertility issues, seeing if child will have genetic issues) The process: 1. Stimulate the ovaries 2. egg and sperm collection 3. fertilisation and nurturing embryos in lab 4. transferring the embryo 5. luteal phase support and pregnancy test ## Footnote * Challenges in IVF : * Prevention of surge of LH leading to ovulation, hence the need for pituitary desensitization with use of GnRH analogue * Prevention of ovarian hyperstimulation syndrome * Contemporary management of IVF look at ways to reduce OHSS as well as reducing side effects from prolong GnRH suppression.

Answer 42

## Footnote - phased out

Answer 43

Glucagon secretion is a major driving force to the metabolic adaptation to starvation. Plasma glucagon level increases after 24–48 h of fasting, inducing hepatic insulin resistance that prevents glucose from being stored. Glucagon also promotes gluconeogenesis and ketogenesis. Increases fatty acid catabolism, inhibits glycolysis and fuels the TCA cycle.

Answer 44

Congenital Adrenal Hyperplasia - Excess in catecholamines - Overall worldwide incidence of Classic CAH is 1 in 15000, 2/3 salt losers - Carrier frequency 1/60 - Non-classic prevalence 1/100 – 1/1000 - Carrier frequency 1/17 - Group of autosomal recessive disorders with impairment of cortisol biosynthesis - 21OH-deficiency accounts for 95% of CAH (CYP21A2 mutations) - Deficiency of 11-ß hydroxylase is found in 9% - Diagnosed based on testing of enzymes often with ACTH stimulation - **Signs and Symptoms:** 1. Classic salt-losing (concomitant aldosterone deficiency) 2. Classic non-salt losing (simple virilizing) 3. Nonclassic (mild or late onset) - **Treatment:** - Glucocorticoids - Mineralocorticoids - Surgery if needed for genital abnormalities

Answer 45

Primary Hyperaldosteronism - First described in the literature in 1956 by Jerome Conn (Conn’s syndrome) - 5-12% of all hypertension - Most common cause of secondary hypertension - Usually presents in 20s-50s - Hypokalaemia common (<50% cases) - **Pathophysiology:** - Adrenocortical hyperplasia (usually bilateral, men, older) - Aldosterone producing adrenal adenoma (unilateral, women, younger) - Familial hyperaldosteronism - Glucocorticoid remediable - Mineralocorticoid excess has additional negative cardiovascular effects - Left ventricular hypertrophy - Cardiovascular events - Myocardial fibrosis - Coronary vasculitis Diagnosis - **Screening:** - Aldosterone to renin ratio - >70 abnormal - Renin should be suppressed (or low) - **Confirmatory testing (must have normal BP & K+):** - Saline suppression test - 2L IV saline over 4 hours - Normal response is to suppress aldosterone - Diagnostic if aldosterone >280 pmol/L - Fludrocortisone suppression test - Oral salt suppression test - Note – most antihypertensives interfere with results - Should only be tested on prazosin, verapamil, or hydralazine (4-6 weeks prior) ## Footnote - **Adrenocortical hyperplasia** - Mineralocorticoid antagonists - Spironolactone - Eplerenone, amiloride, triamterene - Salt-restricted diet, regular exercise, no smoking - **Unilateral adrenal adenoma** - Adrenalectomy - If unsuitable for surgery, use mineralocorticoid antagonists - **Familial hyperaldosteronism** - Low-dose glucocorticoids (for type 1) - Dexamethasone or prednisolone - Mineralocorticoid antagonists

Answer 46

- **Epidemiology:** - Clinical phenotype includes: Adrenaline, noradrenaline, and/or dopamine - <1% of all patients with hypertension, true incidence unknown - 15% are extra-adrenal and known as paragangliomas (along sympathetic ganglia) - Male = Female - **Originate from the chromaffin cells in the adrenal medulla - 15% are extra-adrenal and known as paragangliomas (along sympathetic ganglia) - 10-15% malignant - 25-30% familial (MEN2, VHL, NF1, SDH mutations) - **Clinical Features:** - Hypertension, headache, sweating, palpitations, pallor, tachycardia, tremor, sense of impending doom - **Diagnosis and Management:** - **Diagnosis** - Plasma free metanephrines - 24-hour urinary metanephrines - CT adrenals - ± CT chest, abdomen, and pelvis - MIBG scan – looking for metastatic extra-adrenal disease - PET scan – if known metastatic disease - ? Genetic testing - **Management** - α-blockade - Must be done prior to β-blockade - ≥ 7 days pre-operatively - Phenoxybenzamine (non-reversible) - Prazosin - β-blockade - Only after α-blockade – risk of hypertensive crisis - For control of tachycardia - High salt and fluid intake - Surgery – tumour resection

Answer 47

Normal Growth and Endocrine Control Normal growth is defined as the progression of changes in height, weight, and head circumference that are compatible with established standards for a given population. The progression of growth is interpreted within the context of the genetic potential for a particular child. Growth is regulated by growth hormones, thyroid hormones and steroid hormones. Determinants of Normal Growth Somatic growth and biologic maturation are influenced by several factors that act independently and in concert to modify a child's genetic growth potential. The influence of maternal nutrition and intrauterine environment are reflected primarily in the growth parameters at the time of birth and during the first months of life, whereas genetic factors have an influence later in life. The correlation coefficient between length and adult height is only 0.25 at birth, but increases to 0.8 at two-three years of age. Foetal growth is determined mostly by nutritional factors and placenta: - the placenta acts like an endocrine organ by releasing growth factors and hormones that interact and condition how the foetus is growing - GH and IGF regulate the function of the placenta The correlation coefficient between length and adult height varies with age: - 0.25 at birth - 0.8 at 2-3 years - 0.9 at 14-15 years

Answer 48

- Emotional stability and a secure family environment. - Adequate nutrition. - Absence of chronic disease. - Normal hormonal regulation. - Absence of defects impairing normal cellular or bone growth.

Answer 49

This balance is regulated by neurologic, metabolic, and hormonal influences (glucocorticoids, sex steroids, and thyroxin also influence secretion of GH); numerous neurotransmitters and neuropeptides are involved. In humans, GHBP is the proteolytic product of the extracellular domain of the GHR. The GH molecule binds to cell surface GHR, which dimerizes with another GHR so a single GH molecule is enveloped by two GHR molecules. Over 50 mutations in the GHR have been described in the approximately 250 known patients with GH insensitivity. Most of the growth effect is actually an effect of IGF-I production. Hepatic IGF-I circulates almost entirely bound to IGFBPs, with 1% being free. IGFBP-3 binds about 90% of circulating IGF-I in a ternary complex consisting of IGFBP-3, an acid labile subunit (ALS), and the IGF molecule. ALS and IGFBP-3 are produced in the liver as a direct effect of GH. The ALS stabilizes the IGF–IGFBP3 complex, reduces the passage of IGF-I to the extravascular compartment, and extends its half-life. The GH-IGF axis has metabolic functions and works to: - Increase lipolysis - Increase protein synthesis - Increase glucose levels

Answer 50

There are several stages of growth: 1. Foetal growth, which is regulated by IGF-2 and GH. It is mostly dtemined by maternal nurtition and placenta (in turn regulated by GH and grwoth factors). The largest length grwoth occurs in the 2nd trimester thus any negative influences on the mother during this time will affect length. The average birth length is roughly 50 cm. The birth weight is mainly determined by the 3rd trimester 2. Infancy, occurs within the first two years, and is largely determined by nutrition. The average growth is 35 cm per year. 3. Childhood, in which growth is largely determined by GH. Growth rate decelerates to 5.5 cm/year. Growth either catches up or slows down. Until puberty, boys and girls grow at the same rate 4. Puberty, which is determined by sex steroids and GH. Steroid hormones cause an increase in GH resulting in a growth spurt. When growth is low, weight is gained, and when growth is high, weight is lost. While the growth curve appears linear, velocity varies constantly. The difference between girls and boys is between 10 and 12 cm. Girls enter puberty approximately 2 years earlier.

Answer 51

* [Ca2+] in PLASMA/INTERSTITIUM is what matters * Why? – Think about the role of Ca2+ in the interstitium/plasma? * Muscle function – Ca2+ rapidly enters the myocyte the enable the actin-myosin interaction to enable contraction * Nerve function – Ca2+ rapidly enters the neuron to enable neurotransmitter release * WE NEED TO KEEP THIS WITHIN 2.20-2.55mmol/L

Answer 52

Commensal to the vagina, oral cavity, and GIT Pathology: Very important species for maintaining low pH (ferments simple carbohydrates/CHOs to lactic acid, formic acid, acetic acid, CO2, and alcohol), thereby preventing overgrowth of other commensals & pathogens (↓lactobacilli → vaginal candidiasis, bacterial vaginosis) Characteristics: Anaerobic Acidophilic (pH 3-7) Mesophilic (15-45oC) Appearance: Gram +ve bacilli Non-spore forming Non-motile --- Commensal to the urogenital tract, skin, mouth, and GIT Pathology: Commonly causes superficial, cutaneous, & mucocutaneous infections (incl. vulvovaginitis/vaginitis) Risk factors: antibiotics, diabetes, pregnancy, hormones (OCP/HRT) Symptoms: inflammation, burning, itching and “cheesy” discharge Treatment: topical (or oral) antifungals (-azole drugs) Can also cause serious systemic/invasive mycoses (e.g., immunocompromised, healthcare-associated) Characteristics: Facultative anaerobe Grows in acidic & alkaline conditions Mesophilic, dimorphic fungi Appearance: Gram +ve yeast (large cocci) Often w/ budding and pseudohyphae “Sticks and stones”

Answer 53

Commensal to the vagina Pathology: Common cause of bacterial vaginosis (generally caused by overgrowth of gram-variable anaerobes) Risk factors: decrease in lactobacilli, menses onset, vaginal medications/douching, spermicides, increased number/frequency or new sexual partners Symptoms: excessive, grey watery malodorous (‘fishy’) vaginal discharge; non-painful (vs vaginitis) Diagnosis: Vaginal swab: pH > 4.5, +ve Whiff test (fishy odour when 10% KOH added) Microscopy: ↓lactobacilli, ↑gram-variable coccobacilli, clue cells (squamous cells coated with Gardnerella) Treatment: metronidazole (nucleic acid inhibitor), clindamycin (macrolide) Characteristics: Anaerobe ↑pH favours growth Appearance: Gram-variable coccobacilli --- Commensal to the GIT, and vagina (20-30% of healthy women) Pathology: Most common cause of neonatal septicaemia, meningitis, & pneumonia, colonising 50-70% of exposed newborns (early onset: within 7 days of birth; late onset: up to 7 months) Management: pregnant women screened at 36 weeks → prophylactic antibiotics (penicillin) administered immediately before delivery if +ve Also associated with opportunistic adult infections (skin, soft tissue, urinary tract, bacteraemia) Characteristics: Facultative anaerobe Appearance: Gram +ve cocci in chains β-haemolytic

Answer 54

Prevalence: female predominance, 15-25yrs, less common than chlamydia & gonorrhoea, ↑frequency in Indigenous population Pathology: Causes vaginitis & urethritis Symptoms: 70% asymptomatic or, 5-28 days post-infection, mild irritation to severe inflammation (burning post-urination/ejaculation common) Women: frothy, malodorous (‘musty’) greenish vaginal discharge (men may also experience some discharge), ‘strawberry cervix’ on examination, pre-term labour & low birth weight Diagnosis: motile trophozoites on wet mount vaginal swab light microscopy Treatment: metronidazole or tinidazole

Answer 55

Prevalence: female predominance, 15-30yrs, most common STI reported, ↑frequency in Indigenous population Pathology: Causes cervicitis & urethritis (+ conjunctivitis/trachoma, reactive arthritis; C. pneumoniae causes atypical pneumonia), symptoms 7-14 days post-infection Symptoms: pain on urination, clear/white/cloudy discharge, may have nausea/fever (unlike gonorrhoea) Women: cervicitis (70% asymptomatic), pelvic pain (can lead to PID & infertility) Men: penile urethritis (50% of cases), testicular pain/swelling, epididymitis (rarely → sterility) Diagnosis: urine PCR Treatment: azithromycin (macrolide), doxycycline (tetracycline) Can be transmitted vertically (i.e., to newborn) Characteristics: Obligate intracellular pathogen → cannot culture on inert media (i.e., normal agar) as living cells are required No peptidoglycan layer → gram –ve intracellular cocci & cannot be treated with beta-lactam antibiotics

Answer 56

Prevalence: female predominance, 15-25yrs women/20-30yrs men, most common STI reported, ↑frequency in Indigenous population Pathology: Causes cervicitis & urethritis, prostatitis (+ arthritis, endocarditis, conjunctivitis) w/ symptoms 5-28 days post-infection Symptoms: pain on urination, creamy, purulent discharge Women: 50% asymptomatic, pelvic pain (can lead to PID & infertility), pain with intercourse Diagnosis: urine PCR Treatment: ceftriaxone (cephalosporin) + azithromycin (macrolide) Can be transmitted vertically (i.e., to newborn) Characteristics: Facultative intracellular pathogen → slow growing in culture but still important for antibiotic Gram –ve diplococci

Answer 57

Prevalence: very common (spread from skin-to-skin contact), ↑frequency in Indigenous population Pathology: Causes genital warts (90% caused by HPV 6 & 11) and cervical cancer (70% caused by HPV 16 & 18) Diagnosis: hrHPV (DNA amplification of sample from cervix/vagina) screening program commences at 25yrs old every 5 yrs Treatment: usually self-resolves within 1yr; warts can be frozen off Vaccine: subunit vaccine composed of artificially cultured virus-like particles → 100% effective against infection & 98% against high-grade carcinoma; free for Australians 12-25yrs Characteristics: dsDNA circular genome Replicates within nucleus of cells (basal first), using host machinery Physically integrates into host genome --- Common; able to enter latency (site varies between herpesviruses) → adaptation allows for long-term cell & virus survival Characteristics: dsDNA linear genome Capsid (icosahedral symmetry) Envelope Tegument (between capsid & envelope, packed w/ viral proteins) Treatment: anti-virals (nucleoside analogues) Valaciclovir (Valtrex): HSV-1 & 2, VZV (pro-drug of acyclovir) Famciclov (Famvir): HSV-1 & 2, VZV Ganciclovir: CMV (more toxicity and adverse events)

Answer 58

Prevalence: HSV-1 76% vs HSV-2 12% Pathology: Infects skin, causing cold sores (HSV-1) & genital herpes (HSV-2) Latency site: neurons w/ periodic reactivation → shedding & symptoms Severe manifestations: neonatal (acquired during birth), encephalitis (HSV-1), meningitis (HSV-2) --- Prevalence: HSV-1 76% vs HSV-2 12% Pathology: Primary infection (varicella = chicken pox) is systemic Respiratory spread w/ dissemination to lymph nodes & skin via infected lymphocytes → gains access to nervous system Latency site: sensory ganglia/DRG Reactivation leads to neural and skin infection (zoster = shingles) Immunocompromised/elderly Extreme pain due to nerve damage Managed by live attenuated vaccine at 18 months & booster >60yrs --- Prevalence: high w/ 50-80% infected by 40yrs Pathology: Spread via urine, saliva & breast milk Primary infection is systemic but often asymptomatic Latency site: myeloid progenitors in bone marrow CMV infections during pregnancy cause congenital defects Severe infections in immunocompromised

Answer 59

Prevalence: high w/ 90% of adults infected Pathology: Spread via saliva (‘kissing disease’) Primary infection usually asymptomatic, alternatively causes infectious mononucleosis (aka glandular fever) Latency site: B lymphocytes → oncogenic potential Dangerous in transplant recipients (→ post-transplant lymphoproliferative disease) Associated with cancers (e.g., Hodgkin’s lymphoma, Burkitt’s lymphoma)