MEDICAL CASES

The Female Reproductive System

2009-12-19T09:31:00.000-08:00

Chapter 14 - The Female Reproductive System
Chapter 14
The Female Reproductive System
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Applied anatomy
The pelvis
The bony pelvis is composed of the 2 pelvic bones with the sacrum and coccyx posteriorly. The pelvic brim divides the â€˜false pelvisâ€™ above (part of the abdominal cavity) and the â€˜true pelvisâ€™ below.
Pelvic inlet: also known as the pelvic brim. Formed by the sacral promontory posteriorly, the iliopectineal lines laterally and the symphysis pubis anteriorly.
Pelvic outlet: formed by the coccyx posteriorly, the ischial tuberosities laterally and the pubic arch anteriorly. The pelvic outlet has 3 wide notches. The sciatic notches are divided into the greater and lesser sciatic foramina by the sacrotuberous and sacrospinous ligaments which can be considered part of the perimeter of the outlet clinically.
The pelvic cavity: lies between the inlet and the outlet. It has a deep posterior wall and a shallow anterior wall giving a curved shape.
The contents of the pelvic cavity
The pelvic cavity contains the rectum, sigmoid colon, coils of the ileum, ureters, bladder, female reproductive organs, fascia, and peritoneum.
Female internal genital organs
Vagina
The vagina is a thin-walled distensible, fibromuscular tube that extends upwards and backwards from the vestibule of the vulva to the cervix. It is ~8cm long and lies posterior to the bladder and anterior to the rectum.
The vagina serves as an eliminatory passage for menstrual flow, forms part of the birth canal, and receives the penis during sexual intercourse.
The fornix
This is the vaginal recess around the cervix and is divided into anterior, posterior, and lateral regions which, clinically, provide access points for examining the pelvic organs.
Uterus
The uterus is a thick-walled, hollow, pear-shaped muscular organ consisting of the cervix, body and fundus. In the nulliparous female, it is ~8cm long, ~5cm wide, and ~2.5cm deep. The uterus is covered with peritoneum that forms an anterior uterovesical fold, a fold between the uterus and rectum termed the pouch of Douglas, and the broad ligaments laterally.
The uterus receives, retains, and nourishes the fertilized ovum.
Uterine orientation
In most females, the uterus lies in an anteverted and anteflexed position.
Anteversion: the long axis of the uterus is angled forward.
Retroversion: The fundus and body are angled backwards and therefore lie in the pouch of Douglas. Occurs in about 15% of the female population. A full bladder may mimic retroversion clinically.
Anteflexion: the long axis of the body of the uterus is angled forward on the long axis of the cervix.
Retroflexion: The body of the uterus is angled backward on the cervix
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Fallopian tubes
The fallopian or â€˜uterineâ€™ tubes are paired tubular structures, ~10cm long. The fallopian tubes extend laterally from the cornua of the uterine body, in the upper border of the broad ligament and opens into the peritoneal cavity near the ovaries. The fallopian tube is divided into 4 parts:
Infundibulum: distal, funnel-shaped portion with finger-like â€˜fimbriaeâ€™.
Ampulla: widest and longest part of tube outside the uterus.
Isthmus: thick-walled with a narrow lumen and therefore, least distensible part. Enters the horns of the uterine body.
Intramural: that part which pierces the uterine wall.
The main functions of the uterine tube are to receive the ovum from the ovary, provide a site where fertilization can take place (usually in the ampulla) and transport the ovum from the ampulla to the uterus. The tube also provides nourishment for the fertilized ovum.
Ovaries
The ovaries are whitish-grey, almond-shaped organs measuring ~4cmÃ—2cm which are responsible for the production of the female germ cells, the ova, and the female sex hormones, oestrogen and progesterone.
They are suspended on the posterior layer of the broad ligament by a peritoneal extension (mesovarium) and supported by the suspensory ligament of the ovary (a lateral extension of the broad ligament and mesovarium) and the round ligament which stretches from the lateral wall of the uterus to the medial aspect of the ovary.
Perineum
The perineum lies inferior to the pelvic inlet and is separated from the pelvic cavity by the pelvic diaphragm.
Seen from below with the thighs abducted, it is a diamond-shaped area bounded anteriorly by the pubic symphysis, posteriorly by the tip of the coccyx and laterally by the ischial tuberosities.
The perineum is artificially divided into the anterior urogenital triangle containing the external genitalia in females and an anal triangle containing the anus and ischiorectal fossae.
Female external genital organs
These are sometimes collectively known as the â€˜vulvaâ€™. It consists of:
Labia majora: a pair of fat-filled folds of skin extending on either side of the vaginal vestibule from the mons towards the anus.
Labia minora: a pair of flat folds containing a core of spongy connective tissue with a rich vascular supply. Lie medial to the labia majora.
Vestibule of the vagina: between the labia minora, contains the urethral meatus and vaginal orifice. Receives mucous secretions from the greater and lesser vestibular glands.
Clitoris: short, erectile organ; the female homologue of the male penis. Like the penis, a crus arises from each ischiopubic ramus and join in the midline forming the â€˜bodyâ€™ capped by the sensitive â€˜glansâ€™.
Bulbs of vestibule: 2 masses of elongated erectile tissue, ~3cm long, lying along the sides of the vaginal orifice.
Greater and lesser vestibular glands.
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Applied physiology
The menstrual cycle
Menstruation is the shedding of the functional superficial 2/3 of the endometrium after sex hormone withdrawal. This process, which consists of 3 phases, is typically repeated ~300-400 times during a woman's life. Coordination of the menstrual cycle depends on a complex interplay between the hypothalamus, the pituitary gland, the ovaries, and the uterine endometrium.
Cyclical changes in the endometrium prepare it for implantation in the event of fertilization and menstruation in the absence of fertilization. It should be noted that several other tissues are sensitive to these hormones and undergo cyclical change (e.g. the breasts and the lower part of the urinary tract).
The endometrial cycle can de divided into 3 phasesâ€¦
Phases of the menstrual cycle
The first day of the menses is considered to be day 1 of the menstrual cycle.
The proliferative or follicular phase
This begins at the end of the menstrual phase (usually day 4) and ends at ovulation (days 13-14). During this phase, the endometrium thickens and ovarian follicles mature.
The hypothalamus is the initiator of the follicular phase. Gonadotrophinreleasing hormone (GnRH) is released from the hypothalamus in a pulsatile fashion to the pituitary portal system surrounding the anterior pituitary gland. GnRH causes release of follicle stimulating hormone (FSH). FSH is secreted into the general circulation and interacts with the granulosa cells surrounding the dividing oocytes.
FSH enhances the development of 15-20 follicles each month and interacts with granulosa cells to enhance aromatization of androgens into oestrogen and oestradiol.
Only one follicle with the largest reservoir of oestrogen can withstand the declining FSH environment whilst the remaining follicles undergo atresia at the end of this phase.
Follicular oestrogen synthesis is essential for uterine priming, but is also part of the positive feedback that induces a dramatic preovulatory leuteinising hormone (LH) surge and subsequent ovulation.
The luteal or secretory phase
The luteal phase starts at ovulation and lasts through to day 28 of the menstrual cycle.
The major effects of the LH surge are the conversion of granulosa cells from predominantly androgen-converting cells to predominantly progesterone-synthesising cells. High progesterone levels exert negative feedback on GnRH which, in turn, â†“ FSH/LH secretion.
At the beginning of the luteal phase, progesterone induces the endometrial glands to secrete glycogens, mucus, and other substances. These glands become tortuous and have large lumina due to â†‘ secretory activity. Spiral arterioles extend into the superficial layer of the endometrium.
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In the absence of fertilization by day 23 of the menstrual cycle, the superficial endometrium begins to degenerate and consequently ovarian hormone levels â†“. As oestrogen and progesterone levels fall, the endometrium undergoes involution.
If the corpus luteum is not rescued by human chorionic gonadotrophin (hCG) hormone from the developing placenta, menstruation occurs 14 days after ovulation. If conception occurs, placental hCG maintains luteal function until placental production of progesterone is well established.
The menstrual phase
This phase sees the gradual withdrawal of ovarian sex steroids which causes slight shrinking of the endometrium, and therefore the blood flow of spiral vessels is reduced. This, together with spiral arteriolar spasms, leads to distal endometrial ischaemia and stasis. Extravasation of blood and endometrial tissue breakdown lead to onset of menstruation.
The menstrual phase begins as the spiral arteries rupture, releasing blood into the uterus and the apoptosing endometrium is sloughed off.
During this period, the functionalis layer of the endometrium is completely shed. Arteriolar and venous blood, remnants of endometrial stroma and glands, leucocytes and red blood cells are all present in the menstrual flow.
Shedding usually lasts ~4 days.
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History-taking in gynaecology
It is important to remember that many females can be embarrassed by having to discuss their gynaecological problems, so it is vital to appear confident, friendly, and relaxed.
Although there are parts particular to this history, most of it is the same as the basic outline described in Chapter 2 and we suggest that readers review that chapter before going on.
Demographic details
Name, age, date of birth, occupation.
Presenting complaint
Ask the patient to tell you in her own words what she perceives the main symptom or symptoms to be. Document each in order of severity.
History of presenting complaint
More detailed questioning will depend on the nature of the presenting complaintâ€”see the following pages. As described on p.36 ascertain:
The exact nature of the symptom.
The onset.
When and how it began (e.g. suddenly, graduallyâ€”over how long?)
If longstanding, why is the patient seeking help now?
Periodicity and frequency.
Is the symptom constant or intermittent?
If intermittent, how long does it last each time?
What is the exact manner in which it comes and goes?
â–¶ How does it relate to the menstrual cycle?
Change over time.
Exacerbating and relieving factors.
Associated symptoms.
The degree of functional disability caused.
Menstrual history
Age of menarche (first menstrual period).
Normally about 12 years but can be as early as 9 or as late as 16.
Date of last menstrual period (LMP).
Duration and regularity of periods (cycle).
Normal menstruation lasts 4-7 days.
Average length of menstrual cycle is 28 days (i.e. the time between first day of one period and the first day of the following period) but can vary between 21 and 42 days in normal women.
Menstrual flow: whether light, normal, or heavy (see p.448).
Menstrual pain: whether occurs prior to or at the start of bleeding.
Irregular bleeding.
E.g. intermenstrual blood-loss, post-coital bleeding etc.
Associated symptoms.
Bowel or bladder dysfunction, pain.
Hormonal contraception or HRT.
Age at menopause (if this has occurred).
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Past gynaecological history
Record all details of:
Previous cervical smears, including date of last smear, any abnormal smear results, and treatments received.
Previous gynaecological problems and treatments including surgery and pelvic inflammatory disease.
Contraception
It is also essential to ask sexually active women of reproductive age about contraception, including methods used, duration of use and acceptance, current method, as well as future plans.
Past obstetric history
Gravidity and parity: see p.467 for a full explanation.
Document the specifics of each pregnancy:
Current age of the child and age of mother when pregnant.
Birth weight.
Complications of pregnancy, labour, and puerperium.
Miscarriages and terminations. Note gestation time and complications.
Past medical history
As described in Chapter 2. Pay particular attention to any history of chronic lung or heart disease and make note of all previous surgical procedures.
Drug history
As in Chapter 2. Ask about all medication/drugs taken (prescribed, over the counter and illicit drugs). Record dose, frequency, as well as any known drug allergies.
â–¶ Make particular note to ask about the oral contraceptive pill (OCP) and hormone replacement therapy (HRT) if not done so already.
Family history
Note especially any history of genital tract cancer, breast cancer and diabetes.
Smoking and alcohol
As always, document fully as described on p.44.
Social history
Take a standard SHx including living conditions and marital status.
This is also an extra chance to explore the impact of the presenting problem on the patient's lifeâ€”in terms of their social life, employment, home life, and sexual activity.
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Abnormal bleeding in gynaecology
Menorrhagia
This is defined as >80ml of menstrual blood loss per period (normal = 20-60ml) and may be caused by a variety of local, systemic, or iatrogenic factors. Menorrhagia is hard to measure, but periods are considered â€˜heavyâ€™ if they lead to frequent changes of sanitary towels.
As well as the standard questions for any symptom, ask about:
The number of sanitary pads/towels used per day and the â€˜strengthâ€™ (absorbency) of those pads.
Bleeding through to clothes or onto the bedding at night (â€˜floodingâ€™).
The need to use 2 pads at once.
The need to wear double protection (i.e. pad and tampon together).
Interference with normal activities.
â–¶ Remember to ask about symptoms of iron deficiency anaemia such as lethargy, breathlessness, and dizziness.
Dysmenorrhoea
This is pain associated with menstruationâ€”thought to be caused by â†‘ levels of endometrial prostaglandins during the luteal and menstrual phases of the cycle resulting in uterine contractions. The pain is typically cramping, localized to the lower abdomen and pelvic regions, and radiating to the thighs and back.
Dysmenorrhoea may be primary or secondary:
Primary: occurring from menarche.
Secondary: occurring in females who previously had normal periods (often caused by pelvic pathology).
When taking a history of dysmenorrhoea, take a full pain history as on p.39, a detailed menstrual history ( p.446), and ask especially about the relationship of the pain to the menstrual cycle. Remember to ask about the functional consequences of the painâ€”how does it interfere with normal activities?
Intermenstrual bleeding (IMB)
Intermenstrual bleeding is uterine bleeding which occurs between the menstrual periods.
As for all these symptoms, a full standard battery of questions should be asked ( p.38), as full menstrual history ( p.446), past medical and gynaecological histories ( p.42) and sexual history ( p.408).
Ask also about the association of the bleeding with hormonal therapy, contraceptive use and previous cervical smears.
Postcoital bleeding
This is vaginal bleeding precipitated by sexual intercourse. It can be caused by similar conditions to intermenstrual bleeding. Take a full and detailed history as above.
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Box 14.1 Some causes of menorrhagia
Hypothyroidism.
Intra-uterine contraceptive device (IUCD).
Fibroids.
Endometriosis.
Polypsâ€”cervix, uterus.
Uterine cancer.
Infection (STIs).
Previous sterilization.
Warfarin therapy.
Aspirin.
Non-steroidal anti-inflammatory drugs (NSAIDs).
Clotting disorders (e.g. von-Willebrand's disease).
Box 14.2 Some causes of secondary dysmenorrhoea
Pelvic inflammatory disease.
Endometriosis.
Uterine adenomyosis.
Fibroids.
Endometrial polyps.
Premenstrual syndrome.
Cessation of OCP.
Box 14.3 Some causes of intermenstrual bleeding
Obstetric pregnancy, ectopic pregnancy, gestational trophoblastic disease.
Gynaecological: vaginal malignancy, vaginitis, cervical cancer, adenomyosis, fibroids, ovarian cancer.
Iatrogenic anticoagulants, corticosteroids, antipsychotics, tamoxifen, SSRIs, rifampicin, and anti-epileptic drugs (AEDs).
Box 14.4 Some causes of post-coital bleeding
Similar to intermenstrual bleeding, as well as:
Vaginal infection with Chlamydia, gonorrhoea, trichomaniasis or yeast. Also cervicitis.
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Amenorrhoea
This is the absence of periods and may be â€˜primaryâ€™ or â€˜secondaryâ€™.
Primary: failure to menstruate by 16 years of age in the presence of normal secondary sexual development or failure to menstruate by 14 years in the absence of secondary sexual characteristics.
Secondary: normal menarche, then cessation of menstruation with no periods for at least 6 months.
â–¶ Amenorrhoea is a normal feature in prepubertal girls, pregnancy, during lactation, postmenopausal females, and in some women using hormonal contraception.
History-taking
A full and detailed history should be taken as described on p.446, and Chapter 2. Ask especially about:
Childhood growth and development.
If secondary amenorrhoea:
Age of menarche.
Cycle days.
Day and date of LM P.
Presence or absence of breast soreness.
Mood change immediately before menses.
Chronic illnesses.
Previous surgery (including cervical surgery with can cause stenosis and more obviously oophorectomy and hysterectomy).
Prescribed medications known to cause amenorrhoea such as phenothiazines, domperidone and metoclopramide (produce either hyperprolactinaemia or ovarian failure).
Illicit or â€˜recreationalâ€™ drugs.
Sexual history.
SHx including any emotional stress at school/work/home, exercise and dietâ€”include here any weight gain or weight loss.
Systems enquiry: include vasomotor symptoms, hot flushes, virilizing changes (e.g. â†‘ body hair, greasy skin etc), galactorrhoea, headaches, visual field disturbance, palpitations, nervousness, hearing loss.
Postmenopausal bleeding
This is vaginal bleeding occurring >6 months after the menopause. It requires reassurance and prompt investigation as it could indicate the presence of malignancy.
As well as all the points outlined above, ask about:
Local symptoms of oestrogen deficiency such as vaginal dryness, soreness, and superficial dyspareunia ( p.452).
Itching (pruritus vulvaeâ€”more likely in non-neoplastic disorders).
Presence of lumps or swellings at the vulva.
Cervical or endometrial malignancy
Often present with profuse or continuous vaginal bleeding or with a bloodstained offensive discharge.
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Box 14.5 Some causes of amenorrhoea
Hypothalamic: idiopathic, weight loss, intense exercise.
Hypogonadism from hypothalamic or pituitary damage: tumours, craniopharyngiomas, cranial irradiation, head injuries.
Pituitary: hyperprolactinaemia, hypopituitarism.
Delayed puberty: constitutional delay.
Systemic: chronic illness, weight loss, endocrine disorders (e.g. Cushing's syndrome, thyroid disorders).
Uterine: mullerian agenesis.
Ovarian: PCOS, premature ovarian failure (e.g. Turner's syndrome, autoimmune disease, surgery, chemotherapy, pelvic irradiation, infection).
Psychological: emotional stress at school/home/work.
Box 14.6 Some causes of post-menopausal bleeding
Cervical carcinoma.
Uterine sarcoma.
Vaginal carcinoma.
Endometrial hyperplasia/carcinoma/polyps.
Cervical polyps.
Trauma.
Hormone replacement therapy.
Bleeding disorder.
Vaginal atrophy.
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Other symptoms in gynaecology
Pelvic pain and dyspareunia
As with any type of pain, pelvic pain may be acute or chronic. Chronic pelvic pain is often associated with dyspareunia.
Dyspareunia is painful sexual intercourse and may be experienced superficially at the area of the vulva and introitus on penetration or deep within the pelvis. Dyspareunia can lead to failure to reach orgasm, the avoidance of sexual activity and relationship problems.
Box 14.7 Gynaecological versus gastrointestinal pain
Distinguishing between pain of gynaecological and gastrointestinal origin is often difficult. This is because the uterus, cervix, and adnexa share the same visceral innervation as the lower ileum, sigmoid colon, and rectum. You should be careful in your history to rule out a gastrointestinal problem and keep an open mind.
When taking a history of pelvic pain or dyspareunia, you should obtain a detailed history as for any type of pain ( p.39) including site, radiation, character, severity, mode and rate of onset, duration, frequency, exacerbating factors, relieving factors, and associated symptoms.
You also need to establish the relationship of the pain to the menstrual cycle. Ask also about:
Date of LMP.
Cervical smears.
Intermenstrual or post-coital bleeding.
Previous gynaecological procedures (e.g. IUCD, hysteroscopy).
Previous pelvic inflammatory disease or genitourinary infections.
Previous gynaecological surgery (adhesion formation?).
Vulval discharge.
Bowel habit, nausea, and vomiting ( p.226).
A detailed sexual history ( p.408) should also include contraceptive use and the degree of impact the symptoms have on the patient's normal life, and psychological health.
Vaginal discharge
Vaginal discharge is a common complaint during the child-bearing years. As well as the standard questions ( p.446) ask about:
Colour, volume, odour, and presence of blood.
Irritation.
â–¶ Don't forget to ask about diabetes and obtain a full DHx including recent antibiotic useâ€”both of which may precipitate candidal infection.
Obtain a full sexual history ( p.408). A full gynaecological history should include history of cervical smear testing, use of ring pessaries, and recent history of surgery (â†‘ risk of vesicovaginal fistulae).
â–¶ Lower abdominal pain, backache, and dyspareunia suggest PID.
â–¶ Weight loss and anorexia may indicate underlying malignancy.
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Physiological vaginal discharge
Physiological discharge is usually scanty, mucoid, and odourless. It occurs with the changing oestrogen levels during the menstrual cycle (discharge â†‘ in quantity mid-cycle and is a physiological sign of ovulation) and pregnancy.
It may arise from vestibular gland secretions, vaginal transudate, cervical mucus, and residual menstrual fluid.
Pathological vaginal discharge
This usually represents infection (trichomonal or candidal vaginitis) and may be associated with pruritus or burning of the vulval area.
Candida albicans: the discharge is typically thick and causes itching.
Bacterial vaginitis: the discharge is grey and watery with a fishy smell. Seen especially after intercourse.
Trichomonas vaginalis: the discharge is typically profuse, opaque, cream-coloured and frothy. It also has a characteristic â€˜fishyâ€™ smell. This may also be accompanied by urinary symptoms, such as dysuria and frequency.
Box 14.8 Some causes of dyspareunia
Scars from episiotomy.
Vaginal atrophy.
Vulvitis.
Vulvar vestibulitis.
PID.
Ovarian cysts.
Endometriosis.
Varicose veins in pelvis.
Ectopic pregnancy.
Infections (STIs).
Bladder or urinary tract disorder.
Cancer in the reproductive organs or pelvic region.
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Vulval symptoms
The main symptom to be aware of is itching or irritation of the vulva (pruritis vulvae). It can be debilitating and socially embarrassing. Embarrassment often delays the woman seeking advice.
Causes include infection, vulval dystrophy, neoplasia, and other dermatological conditions. Ask especially about:
The nature of onset, exacerbating and relieving factors.
Abnormal vaginal discharge.
History of cervical intraepithelial neoplasiaâ€”CIN (thought to share a common aetiology with vulval intraepithelial neoplasiaâ€”VIN).
Sexual history.
Dermatological conditions such as psoriasis and eczema.
Symptoms suggestive of renal or liver problems ( p.234).
Diabetes.
Urinary incontinence
This is an objectively demonstrable involuntary loss of urine that can be both a social and hygienic problem.
The two most common causes of urinary incontinence in females are genuine stress incontinence (GSI) and detruser over-activity (DO). Other less commonly encountered causes include mixed GSI and DO, sensory urgency, chronic voiding problems and fistulae.
When taking a history of urinary incontinence, ascertain under what circumstances they experience the symptom. See also p.236. Remember to ask about the functional consequences on the patient's daily life.
Genuine stress incontinence
Patients notice small amounts of urinary leakage with a cough, sneeze, or exercise. One third may also admit to symptoms of DO.
Ask about:
Number of children (â†‘ risk with â†‘ parity).
Genital prolapse.
Previous pelvic floor surgery.
Detruser over-activity
Urge incontinence, urgency, frequency and nocturia (see p.236). Ask about:
History of nocturnal enuresis.
Previous neurological problems.
Previous incontinence surgery.
Incontinence during sexual intercourse.
DHx (see note under â€˜the elderly patientâ€™ p.484).
Overflow incontinence
Voiding disorders can result in chronic retention leading to overflow incontinence and â†‘ predisposition to infection. The patient may complain of hesitancy, straining, poor flow, and incomplete emptying in addition to urgency and frequency.
Fistulae
Suspect if incontinence is continuous during the day and night.
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Genital prolapse
Genital prolapse is descent of the pelvic organs through the pelvic floor into the vaginal canal. In the female genital tract, the type of prolapse is named according to the pelvic organ involved. Some examples include:
Uterine: uterus.
Cystocoele: bladder.
Vaginal vault prolapse: apex of vagina after hysterectomy.
Enterocoele: small bowel.
Rectocoele: rectum.
Mild degrees of genital prolapse are often asymptomatic. More extensive prolapse may cause vaginal pressure or pain, introital bulging, a feeling of â€˜something coming downâ€™, as well as impaired sexual function.
Uterine descent often gives symptoms of backache especially in older patients.
There might be associated symptoms of incomplete bowel emptying (rectocoele) or urinary symptoms such as frequency or incomplete emptying (cystocoele or cysto-urethrocoele).
Box 14.9 Some causes of genital prolapse
Oestrogen deficiency states: such as advancing age and the menopause (atrophy and weakness of the pelvic support structures).
Childbirth: prolonged labour, instrumental delivery, fetal macrosomia, â†‘ parity.
Genetic factors: e.g. spina bifida.
Chronic raised intra-abdominal pressure: e.g. chronic cough, constipation.
Box 14.10 Some other common vulval conditions
Dermatitis: atopic, seborrhoeic, irritant, allergic, steroid-induced (itch, burning, erythema, scale, fissures, lichenification).
Vulvovaginal candidiasis: itch, burning, erythema, vaginal discharge.
Lichen sclerosus: itch, burning, dyspareunia, white plaques, atrophic wrinkled surface.
Psoriasis: remember to look for other areas of psoriasis; scalp, natal cleft, nails.
Vulval intraepithelial neoplasia: itch, burning, multifocal plaques.
Erosive vulvovaginitis: erosive lichen planus, pemphigoid, pemphigus vulgaris, fixed drug eruption (chronic painful erosion and ulcers with superficial bleeding).
Atrophic vaginitis: secondary to oestrogen deficiency (thin, pale, dry vaginal epithelium. Superficial dyspareunia, minor vaginal bleeding and pain).
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Outline gynaecological examination
The gynaecological examination should include a full abdominal examination before proceeding to the pelvic, speculum, and bimanual examinations.
Explain to the patient that you would like to examine their genitalia and reproductive organs and reassure them that the procedure will be quick and gentle.
You should have a chaperone present, particularly if you are male*.
As always, ensure that the room is warm and well lit, preferably with a moveable light source and that you will not be disturbed.
The examination should follow an orderly routine. The authors' suggestion is shown below. It is standard practice to start with the cardiovascular and respiratory systemsâ€”this not only gives a measure of the general health of the patient but establishes a â€˜physical rapportâ€™ before you examine more delicate or embarrassing areas.
Box 14.11 Framework for the gynaecological examination
General inspection.
Cardiorespiratory examination.
Abdominal examination.
Pelvic examination
External genitaliaâ€”inspection.
External genitaliaâ€”palpation.
Speculum examination.
Bimanual examination (â€˜PVâ€™ examination).
â–¶ Perform bedside urinalysis, if able.
* This is controversial at the time of writingâ€”attitudes vary between countries. In the UK, official advice is that all doctors should have a chaperone when performing an intimate examination and the chaperone should be the same sex as the patient. In practice, male doctors performing an examination on a female and females performing an examination on a male should always have a chaperone present whilst the need for a chaperone in other situations is judged at the time.
General inspection and other systems
Always begin with a general examination of the patient (as described in Chapter 3) including temperature, hydration, coloration, nutritional status, lymph nodes, and blood pressure. Note especially:
Distribution of facial and body hair, as hirsutism may be a presenting symptom of various endocrine disorders.
Height and weight.
Examine the cardiovascular and respiratory systems in turn (see Chapters 7 and 8).
Breast examination is a routine part of the procedure in gynaecology in many countries. In the UK, it should be performed ( Chapter 13) if there are symptoms or at first consultation in women over 45 years.
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Abdominal examination
A full abdominal examination should be performed (see Chapter 9). Look especially in the periumbilical region for scars from previous laparoscopies and in the suprapubic region where transverse incisions from caesarean sections and most gynaecological operations are found.
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Pelvic examination
The patient should be allowed to undress in privacy and, if necessary, to empty her bladder first.
Set-up and positioning
Before starting the examination, always explain to the patient what will be involved. Ensure the abdomen is covered. Ensure good lighting and remember to wear disposable gloves.
Ask the patient to lie on her back on an examination couch with both knees bent up and let her knees fall apartâ€”either with her heels together in the middle or separated.
The lithotomy position, in which both thighs are abducted and feet suspended from lithotomy stirrups is usually adopted when performing vaginal surgery.
Examination of the external genitalia
Uncover the mons to expose the external genitalia making note of the pattern of hair distribution.
Apply a lubricating gel to the examining finger.
Separate the labia from above with the forefinger and thumb of your left hand.
Inspect the clitoris, urethral meatus, and vaginal opening.
Look especially for any:
Discharge.
Redness.
Ulceration.
Atrophy.
Old scars.
Ask the patient to cough or strain down and look at the vaginal walls for any prolapse.
Palpation
Palpate the length of the labia majora between the index finger and thumb.
The tissue should feel pliant and fleshy.
Palpate for Bartholin's gland with the index finger of the right hand just inside the introitus and the thumb on the outer aspect of the labium majora.
Batholin's glands are only palpable if the duct becomes obstructed resulting in a painless cystic mass or an acute Bartholin's abscess. The latter is seen as a hot, red, tender swelling in the posterolateral labia majora.
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P.460

Speculum examination
Speculum examination is carried out to see further inside the vagina and to visualize the cervix. It also allows the examiner to take a cervical smear or swabs.
There are different types of vaginal specula (see Fig. 14.1) but the commonest is the Cusco's or bivalve speculum. It is important that you familiarize yourself with the operation of the speculum before examining a patient so that you can concentrate on the findings.
Inserting the speculum
Explain to the patient that you are about to insert the speculum into the vagina and provide reassurance that this should not be painful.
Warm the speculum under running water and lubricate it with a water-based lubricant.
Using the left hand, open the lips of the labia minora to obtain a good view of the introitus.
Hold the speculum in the right hand with the main body of the speculum in the palm (see Fig. 14.2) and the closed blades projecting between index and middle fingers.
Gently insert the speculum into the vagina held with your wrist turned such that the blades are in line with the opening between the labia.
The speculum should be angled downwards and backwards due to the angle of the vagina.
Maintain a posterior angulation and rotate the speculum through 90Â° to position handles anteriorly.
When it cannot be advanced further, maintain a downward pressure and press on the thumb piece to hinge the blades open exposing the cervix and vaginal walls.
Once the optimum position is achieved, tighten the thumbscrew.
Findings
Inspect the cervix which is usually pink, smooth and regular.
Look for the external os (central opening) which is round in the nulliparous female and slit-shaped after childbirth.
Look for cervical erosions which appear as strawberry-red areas spreading circumferentially around the os and represent extension of the endocervical epithelium onto the surface of the cervix.
Identify any ulceration or growths which may suggest cancer.
Cervicitis may give a mucopurulent discharge associated with a red, inflamed cervix which bleeds on contact. Take swabs for culture.
Removing the speculum
â–¶ This should be conducted with as much care as insertion. You should still be examining the vaginal walls as the speculum is withdrawn.
Undo the thumbscrew and withdraw the speculum.
The blades should be held open until their ends are visible distal to the cervix to avoid causing pain.
Rotate the open blades in an anticlockwise direction to ensure that the anterior and posterior walls of the vagina can be inspected.
Near the introitus, allow the blades to close taking care not to pinch the labia or hairs.
P.461

Fig. 14.1 (a) Sim's speculumâ€”used mainly in the examination of women with vaginal prolapse. (b) Cusco's speculum.

Fig. 14.2 Hold the speculum in the right hand such that the handles lie in the palm and the blades project between the index and middle fingers.

Box 14.12 A word about specula
Many departments and clinical areas now used plastic/disposable specula. These do not have a thumb-screw but a ratchet to open/close the blades. Take care to familiarize yourself with the operation of the speculum before starting the examination.
P.462

Bimanual examination
Digital examination helps identify the pelvic organs. Ideally the bladder should be emptied, if not already done so by this stage.
This examination is often known as per vaginam or simply â€˜PVâ€™.
Getting started
Explain again to the patient that you are about to perform an internal examination of the vagina, uterus, tubes, and ovaries and obtain verbal consent.
The patient should be positioned as described on p.457.
Expose the introitus by separating the labia with the thumb and forefinger of the gloved left hand.
Gently introduce the lubricated index and middle fingers of the right hand into the vagina.
Insert your fingers with the palm facing laterally and then rotate 90Â° so that the palm faces upwards.
The thumb should be abducted and the ring and little finger flexed into the palm (see Fig. 14.3).
Vagina, cervix and fornices
Feel the walls of the vagina which are slightly rugose, supple and moist.
Locate the cervixâ€”usually pointing downwards in the upper vagina.
The normal cervix has a similar consistency to the cartilage in the tip of the nose.
Assess the mobility of the cervix by moving it from side to side and note any tenderness (â€˜excitationâ€™) which suggests infection.
Gently palpate the fornices either side of the cervix.
Uterus
Place your left hand on the lower anterior abdominal wall about 4cm above the symphysis pubis.
Move the fingers of your right â€˜internalâ€™ hand to push the cervix upwards and simultaneously press the fingertips of your left â€˜externalâ€™ hand towards the internal fingers.
You should be able to capture the uterus between your 2 hands.
Note the following features of the uterine body:
Size: a uniformly enlarged uterus may represent a pregnancy, fibroid or endometrial tumour.
Shape: multiple fibroids tend to give the uterus a lobulated feel.
Position.
Surface characteristics.
Any tenderness.
â–¶ Remember that an anteverted uterus is easily palpable bimanually but a retroverted uterus may not be.
Assess a retroverted uterus with the internal fingers positioned in the posterior fornix.
Ovaries and fallopian tubes
Position the internal fingers in each lateral fornix (finger pulps facing the anterior abdominal wall) and place your external fingers over each iliac fossa in turn.
P.463

Press the external hand inwards and downwards and the internal fingers upwards and laterally.
Feel the adnexal structures (ovaries and fallopian tubes), assessing size, shape, mobility and tenderness.
Ovaries are firm, ovoid and often palpable. If there is unilateral or bilateral ovarian enlargement, consider benign cysts (smooth and compressible) and malignant ovarian tumours.
Normal fallopian tubes are impalpable.
There may be marked tenderness of the lateral fornices and cervix in acute infection of the fallopian tubes (salpingitis).
Masses
It is often not possible to differentiate between adnexal and uterine masses. However, there are some general rules:
Uterine masses may be felt to move with the cervix when the uterus is shifted upwards while adnexal masses will not.
If suspecting an adnexal mass, there should be a line of separation between the uterus and the mass and the mass should be felt distinctly from the uterus.
Whilst the consistency of the mass may help to distinguish its origin in certain cases, an ultrasound may be necessary.
Finishing the examination
Withdraw your fingers from the vagina.
Inspect the glove for blood or discharge.
Re-drape the genital area and allow the patient to re-dress in privacy-offer them assistance if needed.

Fig. 14.3 Correct position of the fingers of the right hand for per vaginam examination.

Fig. 14.4 Bimanual examination of the uterus.

P.464

Taking a cervical smear
Theory
The UK has a National Screening Program to detect pre-malignant conditions of the cervix. Women between the ages of 20 and 65 years receive an invitation to attend for screening every 3 years. A sample of cells from the squamo-columnar junction are obtained and a cytological examination performed to look for evidence of cerival intraepithelial neoplasia (CIN). This stage of the condition is easily and successfully treated.
The majority of Units are now using liquid based cytology (LBC) in order to minimize the number of inadequate samples.
Equipment
Specula of different sizes.
Disposable gloves.
Request form.
Sampling device-plastic broom (Cervex-BrushÂ®).
Liquid-based cytology vial-preservative for sample.
Patient information leaflet.
Before you start
Ensure the woman understands purpose of examination.
Discuss how and when she will receive the results.
Provide a patient information leaflet.
Document the date of last menstrual period.
Document the use of hormonal treatment (e.g. contraception, HRT).
Record the details of last smear and previous abnormal results.
Ask about irregular bleeding (e.g. post-coital or post-menopausal).
Where appropriate, offer screening for Chlamydia infection (under 25 years, symptomatic).
Procedure
Prepare woman as for vaginal examination remembering to make her comfortable and allow privacyâ€”see p.460.
Write the patient's identification details on LBC vial.
Insert Cusco speculum to identify and visualize cervix as on p.460. Record any abnormal features of the cervix
Insert the plastic broom so that the central bristles of the brush are in the endocervical canal and the outer bristles in contact with the ectocervix (see fig. 14.5).
Using pencil pressure, rotate the brush 5 times in a clockwise direction.
The bristles are bevelled to scrape cells only on clockwise rotation.
Rinse the brush thoroughly in the preservative (ThinPrepÂ®) or break off brush into the preservative (SurePathÂ®).
Place in transport packaging with completed request form.
Remove the speculum as p.460.
Allow the patient to re-dress in privacy.
P.465

Fig. 14.5 The end of a typical cervex-brushÂ®.

Fig. 14.6 Representation of how to use a cervex-brushÂ®. Note that the longer, central bristles are within the cervical canal whist the outer bristles are in contact with the ectocervix.

Box 14.13 Cervical smears in pregnancy
Cervical smears should not be performed during pregnancy. The increase in cervical mucus (and resultant â†“ in the number of cells obtained) usually renders the sample inadequate and the results unreliable.
P.466

History-taking in obstetrics
Although there are parts particular to this history, most is the same as the basic outline described in Chapter 2 and we suggest that readers review that chapter before going on.
The parts of the history detail below are only those that differ from those described in Chapter 2 and earlier in this chapter ( p.446).
Demographic details
Name, age, and date of birth.
Gravidity and parityâ€”see Box 14.15.
Estimated date of delivery (EDD)
The EDD can be calculated from the last menstrual period (LMP) by Naegele's rule*, which assumes a 28-day menstrual cycle.
Box 14.14 Calculating the EDD
Subtract 3 months from the first day of the LMP.
Add on 7 days and 1 year.
If the normal menstrual cycle is <28 days, or >28 days, then an appropriate number of days should be subtracted from or added to the EDD. For example, if the normal cycle is 35 days, 7 days should be added to the EDD.
It is important to also consider at this point any detail that may influence the validity of the EDD as calculated from the LMP; such as:
Was the last period normal?
What is the usual cycle length?
Are the patient's periods usually regular or irregular?
Was the patient using the oral contraceptive pill in the 3 months prior to conception? If so, calculations based on her LMP are unreliable.
* Named after the German Obstetritian, Franz Naegele following its publication in his Lehrbuch der Geburtshuelfe published for midwives in 1830. The formula was actually developed by Harmanni Boerhaave. Boerhaave H. (1744) Praelectiones Academicae in Propias Institutiones Rei Medicae. Von Haller A, ed. GÃ¶ttingen: Vandehoeck. 5 (part 2): 437.
Current pregnancy
About the patient's general health and that of her fetus. If there is a presenting complaint, the details should be documented in full as on p.38. and p.446. Also ask about:
Fetal movements.
Not usually noticed until 20 weeks' gestation in the first pregnancy and 18 weeks' in the second or subsequent pregnancies.
Any important laboratory tests or ultrasound scans.
Include dates and details of all the scans, especially the first scan (dating or nuchal translucency scan).
P.467

Box 14.15 Gravidity and parity
These terms can be confusing and, although it is worth knowing the definitions and how to use them, they should be supplemented with a detailed history and not relied on alone as you may miss subtleties which alter your outlook on the case.
Gravidity
The number of pregnancies (including the present one) to any stage.
Parity
The number of live births (at any stage of gestation) and stillbirths after 24 weeks' gestation.
Pregnancies terminating before 24 weeks' gestation can be written after this number with a plus sign.
Examples
A woman who is currently 20 weeks pregnant and has had 2 normal deliveries:
Gravida 3, Para 2.
A woman who is not pregnant and has had a single live birth and one miscarriage at 17 weeks:
Gravida 2, Para 1+1.
A woman who is currently 25 weeks pregnant, has had 3 normal deliveries, one miscarriage at 9 weeks and a termination at 7 weeks:
Gravida 6, Para 3+2.
Twins
There is some controversy as to how to express twin pregnancies. Most people suggest that they should count as 1 for gravidity and 2 for parityâ€”but you should check your local practice on this.
P.468

Past obstetric history
Ask about all of her previous pregnancies including miscarriages, terminations and ectopic pregnancies.
For each pregnancy, note:
Age of the mother when pregnant.
Antenatal complications.
Duration of pregnancy.
Details of induction of labour.
Duration of labour.
Presentation and method of delivery.
Birth weight and sex of infant.
â–¶ Also enquire about any complications of the puerperal period. The puerperium is the period from the end of the 3rd stage of labour until involution of the uterus is complete (about 6 weeks).
Possible complications include:
Postpartum haemorrhage.
Infections of the genital and urinary tracts.
Deep vein thrombosis.
Perineal complications such as breakdown of the perineal wounds.
Psychological complications (e.g. postnatal depression).
Past gynaecological history
Record all previous gynaecological problems with full details of how the diagnosis was made, treatments received, and the success or otherwise of that treatment.
Record the date of the last cervical smear and any previous abnormal results.
Take a full contraceptive history.
Past medical history
Take a full PMH as on p.42. Note especially those conditions which may have an impact on the pregnancy including:
Diabetes.
Thyroid disorders.
Addison's disease.
Asthma.
Epilepsy.
Hypertension.
Heart disease.
Renal disease.
Infectious diseases such as TB, HIV, syphilis, and hepatitis.
Identification of such conditions will allow the obstetrician to consider early referral to a specialist for shared care.
All previous operative procedures.
Blood transfusions and receipt of other blood products.
Psychiatric historyâ€”may extend beyond â€˜simpleâ€™ post-natal depression.
P.469

Drug history
Take a full DHx ( p.44) which should include all prescribed medication, over-the-counter medicines, and illicit drugs.
Record any drug allergies and their nature.
If currently pregnant, ensure the patient is taking 400mcg of folic acid daily until 12 weeks' gestation to reduce the incidence of spina bifida.
Smoking and alcohol
A full history should be taken, as always ( p.46).
Family history
FHx is an important aspect of the obstetric history and should not be overlooked.
Ask about any pregnancy-related conditions such as congenital abnormalities, problems following delivery etc.
Ask also about a FHx of diabetes.
â–¶ Ask especially if there are any known hereditary illnesses. Appropriate counselling and investigations such as chorionic villus sampling or amniocentesis may need to be offered.
Social history
A full standard SHx ( p.48) should be taken. Ask about:
Her partnerâ€”age, occupation, health.
How stable the relationship is.
If she is not in a relationship, who will give her support during and after the pregnancy?
Ask if the pregnancy was planned or not.
If she works, enquire about her job and if she has any plans to return to work.
You may also use this opportunity to give advice on regular exercises and the avoidance of certain foods. e.g. tuna (high Mg content) soft cheeses (risk of listeria) calf's liver (high vitamin A content). See the Oxford Handbook of Obstetrics and Gynaecology1 for more details.
1 Arulkumaran (2005). Oxford Handbook of Obstetrics and Gynaecology. Oxford University Press, Oxford.
Box 14.16 A word about deliveries
The verb â€˜to deliverâ€™ is often misused by students of obstetrics as it is often misused by the population at large.
Babies are not delivered.
In fact, the mothers are â€˜delivered ofâ€™ the child-as in being relieved of a burden.
Check your nearest dictionary!
P.470

Presenting symptoms in obstetrics
Bleedingâ€”during pregnancy
Treat as any symptom. In addition, you should build a clear picture of how much blood is being lost, when and how it is affecting the current pregnancy.
After establishing an exact time-line and other details about the symptom, ask about:
Exact nature of the bleeding (fresh/old).
Amount of blood lost.
Number of sanitary pads used daily.
Presence of clots (and, if present, size of those clots).
Presence of pieces of tissue in the blood.
Presence of mucoid discharge.
Fetal movement.
Associated symptoms such as abdominal pain (associated with placental abruption; placenta praevia is painless).
Possible trigger factorsâ€”recent intercourse, injuries.
Any history of cervical abnormalitiesâ€”and the result of the last smear.
Abdominal pain
A full pain history should be taken as on p.39 including site, radiation, character, severity, mode and rate of onset, duration, frequency, exacerbating factors, relieving factors, and associated symptoms.
Take a full obstetric history and systems enquiry. Ask especially about a past history of pre-eclampsia, pre-term labour, peptic ulcer disease, gallstones, appendicectomy, cholecystectomy.
Remember that the pain may be unrelated to the pregnancy so keep an open mind! Causes of abdominal pain in pregnancy include:
Obstetric: preterm/term labour, placental abruption, ligament pain, symphysis pubis dysfunction, pre-eclampsia/HELLP syndrome, acute fatty liver of pregnancy.
Gynaecological: ovarian cyst rupture, torsion, haemorrhage, uterine fibroid degeneration.
Gastrointestinal: constipation, appendicitis, gallstones, cholecystitis, pancreatitis, peptic ulceration.
Genitourinary: cystitis, pyelonephritis, renal stones, renal colic.
Labour pain
This is usually intermittent, regular in frequency and associated with tightening of the abdominal wall.
P.471

Box 14.17 Some causes of vaginal bleeding in early pregnancy
We suggest the reader turns to the Oxford Handbook of Obstetrics and Gynaecology1 for more detail.
Ectopic pregnancy
Symptoms: light bleeding, abdominal pain, fainting if pain and blood loss is severe.
Signs: closed cervix, uterus slightly larger and softer than normal, tender adnexal mass, cervical motion tenderness.
Threatened miscarriage
Symptoms: light bleeding. Sometimes: cramping, lower abdominal pain.
Signs: closed cervix, uterus corresponds to dates. Sometimes, uterus is softer than normal.
Complete miscarriage
Symptoms: light bleeding. Sometimes: light cramping, lower abdominal pain and a history of expulsion of products of conception.
Signs: uterus smaller than dates and softer than normal. Closed cervix.
Incomplete miscarriage
Symptoms: heavy bleeding. Sometimes: cramping lower abdominal pain, partial expulsion of products of conception.
Signs: uterus smaller than dates and cervix dilated.
Molar pregnancy
Symptoms: heavy bleeding, partial expulsion of products of conception which resemble grapes. Sometimes: nausea and vomiting, cramping lower abdominal pain, history of ovarian cysts.
Signs: dilated cervix, uterus larger than dates and softer than normal.
Information adapted from the WHO department of reproductive health research publication, â€˜Vaginal bleeding in early pregnancyâ€™.
1 Arulkumaran (2005). Oxford Handbook of Obstetrics and Gynaecology. Oxford University Press, Oxford.
P.472

Bleeding-after pregnancy
This is called â€˜post-partum haemorrhageâ€™ or PPH.
Primary PPH: >500ml of blood loss within 24 hours following delivery.
Secondary PPH: any excess bleeding between 24 hours and 6 weeks post delivery. (No amount of blood is specified in the definition).
â–¶ Take a full history as for bleeding during pregnancy on p.470. Ask also about symptoms of infectionâ€”an important cause of secondary PPH.
Hypertension
Hypertension is a common and important problem in pregnancy and you should be alert to the possible symptoms which can result from it such as headache, blurred vision, vomiting and epigastric pain after 24 weeks, convulsions or loss of consciousness.
Pregnancy-induced hypertension
Two readings of diastolic blood pressure 90-110, 4 hours apart after 20 weeks gestation. No proteinuria.
Mild proteinuric pregnancy-induced hypertension
Two readings of diastolic blood pressure 90-110, 4 hours apart after 20 weeks gestation and proteinuria 2+.
Severe proteinuric pregnancy-induced hypertension
Diastolic blood pressure 110 or greater after 20 weeks' gestation and proteinuria 3+. Other symptoms may include: hyper-reflexia, headache, clouding of vision, oligura, abdominal pain, pulmonary oedema.
Eclampsia
Convulsions associated with raised blood pressure and/or proteinuria beyond 20 weeks gestation. May be unconscious.
P.473

Box 14.18 Some causes of bleeding in 2nd/3rd trimesters (>24 weeks)
This is known as â€˜antepartum haemorrhageâ€™ (APH). See the Oxford Handbook of Obstetrics and Gynaecology1 for more detail.
Placenta praevia
The placenta is positioned over the lower pole of the uterus, obscuring the cervix. Bleeding is usually after 28 weeks and often precipitated by intercourse. Findings may include a relaxed uterus, fetal presentation not in pelvis and normal fetal condition.
Placental abruption
This is detachment of a normally located placenta from the uterus before the fetus is delivered. Bleeding can occur at any stage of the pregnancy. Possible findings include a tense, tender uterus, â†“ or absent fetal movements, fetal distress, or absent fetal heart sounds.
Box 14.19 Some causes of post-partum haemorrhage
Primary
Uterine atony (most frequent cause).
Genital tract trauma.
Coagulation disorders.
Retained placenta.
Uterine inversion.
Uterine rupture.
Secondary
Retained products of conception.
Endometritis.
Infection.
Box 14.20 Risk factors for post-partum haemorrhage
Nulliparity, multiparity, polyhydramnios, prolonged labour, multiple gestation, previous PPH or APH, pre-eclampsia, coagulation abnormalities, genital tract lacerations, Asian or Hispanic ethnicity.
P.474

Box 14.21 Minor symptoms of pregnancy
These so-called â€˜minorâ€™ symptoms of pregnancy are often experienced by a number of woman as normal, physiological changes occur. This is not to say that they should be ignored as they may point to pathology.
Nausea and vomiting
The severity varies greatly and is more common in multiple pregnancies and molar pregnancies. Persistence of vomiting may suggest pathology such as infections, gastritis, biliary tract disease or hepatitis.
Heartburn/gastro-oesophageal reflux
Heartburn is a frequent complaint during pregnancy due partially to compression of the stomach by the gravid uterus. See p.228.
Constipation
Often secondary to â†‘ progesterone. Improves with gestation ( p.230).
Shortness of breath
Due to dilatation of the bronchial tree secondary to â†‘ progesterone. Peaks at 20-24 weeks. The growing uterus also has an impact. Other possible causes (such as PE) need to be considered. See p.198.
Fatigue
Very common in early pregnancy, peaking at the end of the first trimester. Fatigue in late pregnancy may be due to anaemia.
Insomnia
Due to anxiety, hormonal changes and physical discomfort.
Pruritus
Generalized itching in the third trimester may resolve after delivery. Biliary problems should be excluded ( p.234).
Haemorrhoids
May resolve after delivery.
Varicose veins
Especially at the feet and ankles.
Vaginal discharge
Exclude infection and spontaneous rupture of the membranes.
Pelvic pain
Stretching of pelvic structures can cause ligament pain which resolves in the second half of the pregnancy. Symphysis-pubis dysfunction causes pain on abduction and rotation at the hips and on mobilization.
Backache
Often first develops during the 5-7th months of pregnancy.
Peripheral paraesthesiae
Fluid retention can lead to compression of peripheral nerves such as carpal tunnel syndrome. Other nerves can be affected, e.g. lateral cutaneous nerve of the thigh.
P.475

P.476

Outline obstetric examination
Explain to the patient that you would like to examine their womb and baby and reassure them that the procedure will be quick and gentle.
You should have a chaperone present, particularly if you are male.
As always, ensure that the room is warm and well lit, preferably with a moveable light source and that you will not be disturbed.
As for the gynaecological examination, you should follow an orderly routine. The authors' suggestion is shown below. It is standard practice to start with the cardiovascular and respiratory systems-this not only gives a measure of the general health of the patient but establishes a â€˜physical rapportâ€™ before you examine more delicate or embarrassing areas.
Box 14.22 Framework for the obstetric examination
General inspection.
Cardiorespiratory examination.
Abdominal inspection.
Abdominal palpation.
Uterine size.
Fetal lie.
Fetal presentation.
Engagement.
Amniotic fluid estimation.
Auscultation of the fetal heart.
Vaginal examination.
â–¶ Perform bedside urinalysis (particularly protein) if able.
General inspection
Always begin with a general examination of the patient (as in Chapter 3) including temperature, hydration, coloration, nutritional status, lymph nodes, and blood pressure. Note especially:
Any brownish pigmentation over the forehead and cheeks known as chloasma.
Distribution of facial and body hair, as hirsutism may be a presenting symptom of various endocrine disorders.
Height, weight, and calculate BMI ( p.66).
â–¶ Blood pressure should be measured in the left lateral position at 45Â° to avoid compression of the IVC by the gravid uterus.
Anaemia is a common complication of pregnancy so examine the mucosal surfaces and conjunctivae carefully ( p.58).
Examine the cardiovascular and respiratory systems in turn (see Chapters 7 and 8).
Flow murmurs are common in pregnancy and, although usually of no clinical significance, must be recorded in detail.
A routine breast examination is not normally indicated unless a female patient complains of breast symptoms, in which case you must carefully look for any pathology such as cysts or solid nodules.
P.477

P.478

Abdominal examination
Inspection
Look for the abdominal distension caused by the gravid uterus rising from the pelvis. Look also for:
Asymmetry.
Fetal movements.
Surgical scars.
Pubic hairline (transverse suprapubic Pfannenstiel incision).
Paraumbilical region (laparoscopic scars).
Cutaneous signs of pregnancy including:
Linea nigra (black line) which stretches from the pubic symphysis upwards in the midline.
Red stretch marks of current pregnancy (striae gravidarum).
White stretch marks (striae albicans) from a previous pregnancy.
Other areas that can undergo pigmentation in pregnancy include the nipples, vulva, umbilicus and recent abdominal scars.
Umbilical changes:
Flattening as pregnancy advances.
Eversion secondary to â†‘ intra-abdominal pressure (e.g. caused by multiple pregnancies or polyhydraminios).
Palpation
Before palpating the abdomen, always enquire about any areas of tenderness and visit those areas last.
Palpation should start as for any standard abdominal examination (Chapter 9) before proceeding to more specific manoeuvres in an obstetric examination.
Uterine size
This provides an estimation of gestational age in weeks and is objectively measured and expressed in centimetres as the symphysial-fundal height (the distance from the symphysis pubis to the upper edge of the uterus).
Box 14.23 The symphysial-fundal height (cm) â‰ˆ weeks of gestation
Between 16-36 weeks, there is a margin of error of Â±2cm, Â±3cm at 36-40 weeks, and Â±4cm at 40 weeks onwards.
You need a tape-measure for this-don't start without it!
Use the ulnar border of the left hand to press firmly into the abdomen just below the sternum.
Move the hand down the abdomen in small steps until you can feel the fundus of the uterus.
Locate the upper border of the bony pubic symphysis by palpating downward in the midline starting from a few centimetres above the pubic hair margin.
Measure the distance between the two points that you have found in centimetres using a flexible tape-measure.
P.479

Fig. 14.7 The distance between the fundus (upper border of the uterus) and the pubic symphysis can be used as a guide to the number of weeks' gestation. You can also, therefore, judge whetherthe uterus is smaller or largerthan expected which may point to problems with the pregnancy.

Box 14.24 Uterine sizeâ€”milestones
The uterus first becomes palpable at 12 weeks' gestation.
20 weeks' gestation = at the level of the umbilicus.
36 weeks' gestation = at the level of the xiphisternum.
P.480

Fetal lie
This describes the relationship between the long axis of the fetus and the long axis of the uterus and, in general, can be:
Longitudinal: the long axis of the fetus matches the long axis of the uterus. Either the head or the breech will be palpable over the pelvic inlet.
Transverse: the fetus lies at right angles to the uterus and the fetal poles are palpable in the flanks.
Oblique: the long axis of the fetus lies at an angle of 45Â° to the long axis of the uterus, the presenting part will be palpable in one of the iliac fossae.
Examination technique
The best position is to stand at the mother's right side, facing her feet.
Put your left hand along the left side of the uterus.
Put your right hand on the right side of the uterus.
Palpate systematically towards the midline with one and then the other handâ€”use â€˜dippingâ€™ movements with flexion of the MCP joints to feel the fetus within the amniotic fluid.
You should feel the fetal back as firm resistance or the irregular shape of the limbs.
You should now palpate more widely using the 2-handed technique above to stabilize the uterus and attempt to locate the head and the breech.
The head can be felt as a smooth, round object that is ballotableâ€”that is, it can be â€˜bouncedâ€™ (gently) between your hands.
The breech is softer, less discrete and is not ballotable.
Fetal presentation
This is the part of the fetus that presents to the mother's pelvis. Possible presenting parts include:
Head: â€˜cepahalicâ€™ presentation. One option in a longitudinal lie.
Breech: â€˜podalicâ€™ presentation. The other option in a longitudinal lie.
Shoulder: seen in a transverse lie.
Examination technique
Stand at the mother's right side, facing her feet.
Place both hands on either side of the lower part of the uterus
Bring the hands together firmly but gently.
You should be able to feel either the head, breech, or other part as described above under â€˜fetal lieâ€™.
It is also possible to use a one-handed technique (Paulik's grip) to feel for the presenting partâ€”this is best left to obstetricians. In this, you use a cupped right hand to hold the lower pole of the uterus. This is possible in ~95% of pregnancies at about 40 weeks.
P.481

Fig. 14.8 Some examples of fetal lie.

P.482

Engagement
When the widest part of the fetal skull is within the pelvic inlet, the fetal head is said to be â€˜engagedâ€™.
In a cephalic presentation, palpation of the head is assessed and expressed as the number of fifths of the skull palpable above the pelvic brim. A fifth of a fetal skull is roughly equal to a finger breath on an adult hand.
The head is engaged when 3 or more fifths are within the pelvic inletâ€”that is when 2 or less fifths are palpable.
When 3 or more fifths are palpable, the head is not engaged.
Number of fetuses
The number of fetuses present can be calculated by assessing the number of fetal poles (head or breech) present.
If there is one fetus present, 2 poles should be palpable (unless the presenting part is deeply engaged).
In a multiple pregnancy, you should be able to feel all the poles except oneâ€”as one is usually tucked away out of reach.
Amniotic fluid/liquor volume estimation
The ease with which fetal parts are palpable can give an indication as to the possibility of â†“ or â†‘ amniotic fluid volume.
â†‘ volume will give a large-for-dates uterus that is smooth and rounded. The fetal parts may be almost impossible to palpate.
â†“ volume may give a small-for-dates uterus. The fetus will be easily palpable giving an irregular, firm outline to the uterus.
Percussion
This is usually unhelpful in an obstetric examination unless you suspect polyhydramnios (increased amniotic fluid volume), in which case, you may wish to attempt to elicit a fluid thrill ( p.260).
Auscultation
Auscultation is used to listen to the fetal heart rate (FHR). This is usually performed using an electronic hand-held Doppler fetal heart rate monitor and can be used as early as 14 weeks.
Using Pinard's fetal stethoscope
A Pinard's fetal stethoscope is not useful until 28 weeks' gestation. It is a simple-looking device rather like an old-fashioned ear-trumpet (Fig. 14.9).
Place the bell of the instrument over the anterior fetal shoulderâ€”where the fetal heart sounds are best heard.
Press your left ear against the stethoscope so as to hold it between your head and the mother's abdomen in a â€˜hands-freeâ€™ position or hold the instrument lightly with one hand.
Press against the opposite side of the mother's abdomen with your other hand so as to stabilize the uterus.
It should sound like a distant ticking noise. The rate varies between 110 and 150/minute at term and should be regular.
â–¶ Record the rate and rhythm of the fetal heart.
P.483

Vaginal examination
Vaginal examination allows you to assess cervical status before induction of labour. You should attempt this only under adequate supervision if you are unsure of the procedure.
This examination allows you to assess the degree of cervical dilatation (in centimetres) using the examining fingers.
Examination of the vagina and cervix should be performed under aseptic conditions in the presence of ruptured membranes or in cases with abnormal vaginal discharge.
Technique
The examination should be performed as described on p.462. The findings take experience to recognize. The student should not shy away from this examination due to its intimate nature.
Findings
Assess:
Degree of dilation.
Full dilation of the cervix is equivalent to 10cm.
Most obstetric departments will have plastic models of cervices in various stages of dilatation which you can practice feeling.
The length of the cervix.
Normal ~3cm but shortens as the cervix effaces secondary to uterine contraction.
The consistency of the cervix which can be described as:
Firm.
Mid-consistency.
Soft (this consistency facilitates effacement and dilatation).
Position.
As the cervix undergoes effacement and dilatation it tends to be pulled from a posterior to an anterior position.
Station of the presenting part.
The level of the head above or below the ischial spines which may be estimated in centimetres.

Fig. 14.9 A Pinard's stethoscope.

P.484

The elderly patient
It is easy to be seduced into thinking that the principal focus should be on very â€˜medicalâ€™ diagnoses such as urinary tract infections, which contribute to significant morbidity (and mortality) in older people.
Continence issues are sadly overlooked in most clinical assessmentsâ€”despite costing the UK National Health Service Â£424m per annum (on figures from 2000). Large-scale surveys of prevalence have shown up to 20% of women over 40 reporting difficulties with continence; so whilst more common in older people, you should always be mindful of problems in younger adults too.
Although continence issues are one of the â€˜Geriatric Giantsâ€™ of disease presentation, it is important to recall the physiology of the post menopausal changesâ€”such as vaginal atrophy and loss of secretionsâ€”which can complicate urinary tract infections, continence and utero-vaginal prolapse in older patients.
Assessment
Tact and understanding: although problems are common, patients may be reluctant to discuss them, or have them discussed in front of others. Engaging in a discussion about bladder and/or sexual function can seem dauntingâ€”but if done empathetically, remembering never to appear to judge, or be embarrassedâ€”you may reveal problems that have seriously affected your patient's quality of life. Treating problems such as these, even with very simple interventions, can be of immeasurable value to the patient.
Holistic assessment of urinary problems: learn to think when asking about bladder function, and work out a pattern of dysfunctionâ€”e.g. bladder instability or stress incontinence. Remember that bladder function may be disrupted by drugs, pain, lack of privacy. Continence issues may reflect poor mobility, visual and cognitive decline.
Genital symptoms: never forget to consider vaginal or uterine pathologyâ€”view postmenopausal bleeding with suspicion. Discharges may represent active infection (if candidaâ€”consider diabetes) or atrophic vaginitis (see opposite).
Past medical history: pregnancies and previous surgery in particular may help point to a diagnosis of stress incontinence. Are urinary tract infections recurrentâ€”has bladder pathology been excluded?
Drugs: many are obviousâ€”diuretics and anticholinergics; some are more subtleâ€”sedatives may provoke nocturnal loss of continence; Does your patient drink tea or coffee?
Tailored functional history: the cornerstone of these pagesâ€”and of any assessment you perform. This largely relates to bladder functionâ€”is the lavatory up or down? How are the stairs? Does your patient already have continence aidsâ€”bottles/commodes/pads, and do they manage with them?
P.485

Box 14.25 A word on atrophic vaginitis
Up to 40% of postmenopausal women will have symptoms and signs of atrophic vaginitis and the vast majority will be elderly and may be reluctant to discuss this with their doctors. A result of oestrogen deficiency, the subsequent â†‘ vaginal pH and thinned endometrium lead to both genital and urinary symptoms and signs. â†“ in vaginal lubrication presents with dryness, pruritus, and discharges, accompanied by an â†‘ rate of prolapse. Urinary complications can result in frequency, stress incontinence, and infections.
Careful physical examination often makes the diagnosis clear with labial dryness, loss of skin turgidity, and smooth, shiny vaginal epithelium. A range of treatment options including topical oestrogens, simple lubricants, and continued sexual activity when appropriate are all key interventions to manage this common condition.
We thank Dr Richard Fuller for providing this page.

CASE 6

2009-09-15T10:29:00.000-07:00

A 79-year-old woman presents to the emergency department (ED) with a chief complaint of a 3-day history of left hip pain. She only mildly twisted her left leg 3 days ago; she has since had increasing pain and difficulty walking. The pain is sharp and radiates down to her left knee. It is mild when she is at rest, but it becomes severe when she attempts to walk. She has not had any weakness or numbness. She denies having any fevers. She has not had any direct trauma to the hip or falls, and there has not been any notable swelling of the leg or skin changes/rash. The review of systems also reveals that she has unintentionally lost 8.8 lb (4.0 kg) over the last 6 months. She denies having any nausea, vomiting, night sweats, cough, or shortness of breath. She has a history of multiple rib fractures that resulted from vigorous coughing 2 years ago; at that time, she was diagnosed only with osteoporosis as the cause of these fractures. She denies having any previous fractures otherwise. Her past medical history also includes chronic obstructive pulmonary disease (COPD), although she has never been a smoker. She also has known osteoarthritis of the hips, scoliosis of the thoracic spine, and a presumptive diagnosis of Paget disease on the basis of a single elevated serum alkaline phosphatase. Her medications include budesonide/eformoterol and terbutaline inhalers, oral calcium and vitamin D supplements, and weekly alendronate. A bisphosphonate was started after dual-energy x-ray absorptiometry (DXA) showed a T score of -2, which is consistent with osteopenia. Both her mother and sister had broken their hips later in their lives. She lives independently and is still driving. She denies experiencing physical abuse, and there are several family members accompanying her in the ED who show concern for her.

On physical examination, the patient appears well and is lying comfortably in bed. Her heart rate is 84 bpm and regular, with a blood pressure of 140/80 mm Hg. Her temperature is normal at 98.9°F (37.2°C), and her respiratory rate is 14 breaths/min. Her cardiovascular, respiratory, and abdominal examinations are all normal. She has moderate pain with any movement of the left leg and has groin tenderness on palpation. The left leg is shortened and externally rotated. Her peripheral pulses are palpable, and she has normal distal strength and sensation in the left lower extremity.

Her blood tests reveal a normal complete blood cell (CBC) count; however, her electrolytes show a significantly depleted phosphate concentration of 0.9 mg/dL (0.29 mmol/L; normal range, 3-4.5 mg/dL). Additional laboratory results include a creatinine of 0.68 mg/dL (60 μmol/L; normal range, <1.5 mg/dL), adjusted calcium of 8.88 mg/dL (2.22 mmol/L; normal range, 9.0–10.5 mg/dL), albumin of 3.6 g/dL (36 g/L; normal range, 3.5-5.5 g/dL), alkaline phosphatase of 350 U/L (normal range, 30-120 U/L), vitamin D (25-hydroxy) of 22.04 ng/mL (55 nmol/L; normal range, 10-68 ng/mL), and a parathyroid hormone of 107.3 pg/mL (107.3 ng/L; normal range, 10-60 pg/mL).

A chest radiograph reveals multiple healed rib fractures. Radiographs of the pelvis and left hip are obtained as well, which reveal a left femoral neck fracture.

What is the underlying disorder that resulted in the patient's pathologic hip fracture?

Hint: The serum phosphate is low, but the serum calcium is preserved.

Vitamin D deficiency

Oncogenic osteomalacia

Fanconi syndrome

Secondary hyperparathyroidism

CASE 5

2009-07-26T07:24:00.000-07:00

A 38-year-old man with altered mental status is brought to the emergency department (ED) by ambulance. The patient had been found sprawled on the stoop of an apartment building when residents called the police. The patient was unresponsive when the paramedics arrived, and they were unable to obtain any additional history from the patient or from any of the onlookers at the scene. The patient was wrapped in blankets and an intravenous (IV) line was inserted, which provided 0.5 L of normal saline during transit to the ED. When the patient was found, the temperature outside was about 35°F (1.7°C), with winds reaching speeds of 10-15 miles per hour (16.1-24.1 kilometers per hour).

On his arrival to the ED, the patient's vital signs are a blood pressure of 88/40 mm Hg, heart rate of 38 bpm, and a respiratory rate of 24 breaths/min. An oral thermometer reading is unsuccessful, but a rectal probe records a temperature of 85.4°F (29.7°C). Repeated attempts to obtain an oxygen saturation measurement via a finger pulse oximeter are not successful. On initial examination, the patient appears to be a homeless, disheveled man with the faint smell of alcohol on his breath. His clothing is stained and extensively worn. He looks older than the stated age on his identification card. In the ED, he is mildly arousable and has trouble following simple commands. He has intact gag and corneal reflexes and does not fight the examiner during the tests. He responds appropriately to painful stimuli. His pupils are equal, round, and reactive to light. No obvious signs of head trauma are noted, and his oropharynx, nares, and ears are unremarkable. His cardiac examination is notable for marked bradycardia of 45 bpm, but no murmurs, rubs, gallops, or extra heart sounds are otherwise noted. A lung examination reveals rhonchi and dullness to percussion in the right lower lung field, but otherwise normal lung sounds. His abdomen is soft, nontender, and nondistended, and normal bowel sounds are heard. The patient's skin is cold and his fingers and toes have a bluish tinge, with a delayed capillary refill time. A brief skin survey reveals some minor abrasions, but no major wounds or erosions. The patient is unable to provide any additional information about his past medical, family, medication, social, or allergy history. His pockets contain an identification card, but no other useful information.

Routine blood work is ordered. The results of his metabolic panel are all within normal limits. His blood glucose level is 104 mg/dL (5.77 mmol/L). His complete blood cell count (CBC) reveals a small elevation in the white blood cell (WBC) count, but it is otherwise unremarkable. A portable chest radiograph shows a small consolidation of the right lower lobe that is consistent with pneumonia.

An electrocardiogram (ECG) is performed

DIAGNOSIS OF CASE 4

2009-07-26T07:12:00.000-07:00

This patient's ECG showed atrial fibrillation with a rapid ventricular response, which is a possible cardiac manifestation of thyrotoxicosis. No ischemic changes were noted despite her rapid heart rate. Her laboratory studies confirmed the suspected diagnosis, with findings of a markedly depressed thyroid-stimulating hormone (TSH) of 0.006 mIU/L (normal range, 0.5-5.0 mIU/L) and elevated triiodothyronine (T3) and thyroxine (T4) concentrations of 632 ng/dL (9.73 nmol/L) and 23.7 ug/dL (305.02 nmol/L), respectively (normal ranges, T3: 70-170 ng/dL; T4: 5-11 ug/dL).
Thyrotoxicosis refers to an elevated concentration of thyroid hormone as well as the related clinical manifestations. This is differentiated from thyroid storm, a life-threatening manifestation of thyrotoxicosis in which a markedly hypermetabolic state is present. Hyperthyroidism most commonly results from uncontrolled Graves disease, in which autoantibodies to the TSH receptor are produced. This leads to excessive thyroid hormone production from the thyroid gland and a reflexive inhibition of TSH release from the pituitary gland. Other etiologies can include a solitary thyroid adenoma, toxic multinodular goiter, hypersecretory thyroid carcinoma, thyrotropin-secreting pituitary adenoma, struma ovarii, and iodine or amiodarone administration. A precipitating event, such as surgery, trauma, myocardial infarction, pulmonary embolism, diabetic ketoacidosis, childbirth, severe infection, discontinuation of antithyroid medication, or thyroid surgery on a patient with uncontrolled hyperthyroidism, is often needed to push a patient with hyperthyroidism into thyroid storm.[1,3]
The incidence of hyperthyroidism in the United States is 0.05% to 1.3%, most of which remains undiagnosed. Approximately 1-2% of these patients will progress to thyroid storm at some point. The prevalence is slightly higher in women compared with men and in white and Hispanic populations compared with black populations. Thyroid storm is most common in the third to sixth decades of life, although it can occur at any age.[1]
Thyroid storm is a clinical diagnosis and, considering the acuity of this life-threatening condition, patients with thyrotoxicosis should be treated empirically when the diagnosis is suspected. Symptoms of thyrotoxicosis include weight loss, palpitations, hair loss, diplopia, chest pain, oligomenorrhea, or confusion. The physical examination reveals a hypermetabolic state, with abnormalities involving multiple organ systems. These findings commonly include hyperpyrexia, tachycardia, tachypnea, and hypertension. Other findings may include fine tremor, exophthalmos, ophthalmoplegia, pretibial edema, congestive heart failure, thyromegaly, thyroid bruit, and hyperreflexia.[2] Laboratory studies show a low TSH level and elevated T3 and T4 concentrations. TSH is the most precise indicator of thyroid function because of the very high sensitivity of the thyroid-pituitary feedback loop, and current assays are able to detect levels of 0.02 mIU/L or less. As such, a normal TSH level largely excludes significant thyroid disease. Other laboratory findings seen in thyrotoxicosis may include hyperglycemia, hypercalcemia, leukocytosis, and elevated liver enzymes.[3] Further testing may be indicated as part of a search for the precipitating cause of clinical decompensation, such as infection, myocardial infarction, or diabetic ketoacidosis. Electrocardiography most often reveals sinus tachycardia or atrial fibrillation. Although thyroid storm requires more rapid and aggressive therapy than thyrotoxicosis, differentiating between the two can sometimes be difficult, as it was in this patient. Burch and Wartofsky developed a scoring system to assist in making this distinction that takes into account thermoregulatory dysfunction, central nervous system effects, gastrointestinal dysfunction, the degree of tachycardia, the extent of congestive heart failure, the presence of atrial fibrillation, and the presence or absence of a precipitating event.[4]
Cardiac complications from thyrotoxicosis include arrhythmias, congestive heart failure, and pulmonary hypertension. The most common arrhythmia in thyrotoxicosis is sinus tachycardia; however, atrial fibrillation occurs in 10-20% of patients with thyrotoxicosis, most often in patients who are older than 60 years. Risk factors for atrial fibrillation in these patients include male sex, increasing age, coronary heart disease, heart failure, and structural heart or valvular disease. Congestive heart failure in thyrotoxicosis is predominantly caused by either persistent tachyarrhythmias (tachycardia-induced cardiomyopathy) or uncontrolled hypertension as a consequence of thyrotoxicosis. Systolic dysfunction can occur as a consequence of the persistent cardiac arrhythmias, but it usually resolves once the hyperthyroid state is treated. Pulmonary hypertension can also occur in thyrotoxicosis, either as a result of a primary effect of thyroid hormone on pulmonary arteriolar resistance vessels, decompensated left heart failure, or via increased pulmonary arterial blood flow (high-output).[1]
The differential diagnosis for thyrotoxicosis and thyroid storm may include anxiety, congestive heart failure, heat exhaustion or heatstroke, factitious disorder, neuroleptic malignant syndrome, panic disorder, septic shock, serotonin syndrome, anticholinergic or sympathomimetic toxicity, and alcohol or benzodiazepine withdrawal syndromes.[5] Because infection is a common trigger for thyroid storm, an initial misdiagnosis of sepsis is not uncommon because of similar characteristics, such as tachycardia, fever, and altered mental status.
Management of thyrotoxicosis consists of a 5-pronged, ordered approach, targeting each step in the biosynthetic pathway of thyroid hormone and its activity on target tissues. Treatment begins with administration of propylthiouracil (PTU) or methimazole, both of which act by inhibiting new hormone synthesis. PTU has the added effect of decreasing peripheral T4 to T3 conversion. Beta-blockers are then employed to inhibit target activity of thyroid hormone. Propranolol is the preferred agent because it also blocks peripheral conversion of T4. When cardioselective agents are preferred, atenolol or metoprolol may be used. At least 1 hour after administration of PTU or methimazole, the patient may be given iodide to inhibit further thyroid hormone release. It is imperative that iodine be given only after synthesis of new hormone is blocked because iodide administration can have the undesired effect of increasing new hormone synthesis. Potassium iodide or Lugol solution of iodine is recommended. Peripheral conversion of T4 to T3 is blocked, as noted above, and dexamethasone may be used as well. Further treatment is supportive and may include acetaminophen for fever and hydrocortisone if the patient is hypotensive as a result of adrenal insufficiency. Salicylates are contraindicated because they displace bound thyroid hormone in the blood.[2,3]
With regard to the management of cardiac symptoms related to thyrotoxicosis, treatment is focused on reducing adrenergic drive to the heart and restoring normal cardiac rhythm. As mentioned above, beta-blockers are very effective for rapid hemodynamic improvement. Either propranolol or metoprolol given intravenously can be used to improve heart rate control either in sinus tachycardia or atrial fibrillation. In severe cases, a continuous infusion of esmolol may be required for rate control. Amiodarone should be avoided when treating atrial fibrillation from thyrotoxicosis because of its high iodine content, which may induce or exacerbate thyroid storm. If a patient is hemodynamically unstable from atrial fibrillation, direct current cardioversion should be employed. If symptoms of pulmonary congestion appear, diuretics may be used. Other drugs for heart failure (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and/or aldosterone receptor antagonists) are reasonable agents in patients who have depressed left ventricular systolic function. Anticoagulation is recommended for patients in atrial fibrillation secondary to thyrotoxicosis. The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines recommend anticoagulation with warfarin to an international normalized ratio of 2.0-3.0 until the patient is euthyroid, after which recommendations and risk stratification are the same for atrial fibrillation without thyrotoxicosis.[2] Of note, PTU, methimazole, and iodide solutions are all classified as pregnancy class D and, as such, should not be used in pregnancy.
This patient's clinical presentation bordered between thyrotoxicosis and thyroid storm, and she was hemodynamically stable. She was immediately treated with propranolol and PTU and was admitted to a monitored bed in the medical service. Because her clinical condition improved and she remained stable, the admitting team chose to forgo further therapy with iodine and steroids. Her atrial fibrillation resolved within 12 hours, but an echocardiogram revealed cardiomyopathy with a left ventricular ejection fraction of 45% that was attributed to her long-standing hyperthyroidism. A diagnosis of Graves disease was made. She was continued on methimazole and metoprolol, and anticoagulation was initiated. Five months later, the patient was still taking methimazole. Her thyroid function had normalized, her cardiomyopathy had reversed, and her anticoagulation was discontinued because atrial fibrillation did not recur. Incidentally, she was ruled out for tuberculosis during her admission with 3 induced sputum samples.

CASE 4 Tachycardia in a 61-Year-Old Woman Background

2009-07-08T03:08:00.000-07:00

A 61-year-old woman presents to the emergency department (ED) after being referred from her primary care provider's (PCP) office for evaluation of tachycardia. She had been seen by her PCP for routine placement of a purified protein derivative (PPD) tuberculin skin test and was incidentally noted to have a pulse of 160 bpm. The patient currently denies any specific complaints other than occasional palpitations. On review of her systems, however, she notes having night sweats; a 110-lb (50-kg) weight loss over the preceding 12 months; and 2-3 months of anxiety, diarrhea, and occasional diplopia. She denies having any fever, chills, chest pain, dyspnea, or swelling in her extremities. She has a past medical history of an unspecified thyroid problem. She does not take any daily medications and has no medication allergies. She has a 50-pack-year smoking history, with occasional alcohol consumption. She had been homeless for a period of time but is currently living in an apartment.
On examination, the patient is awake and fully oriented. She is diaphoretic but in no apparent distress. Her temperature is 97.0°F (36.1°C); her pulse is 160 bpm; her respiratory rate is 24 breaths/min, with an oxygen saturation of 98%; and her blood pressure is 190/117 mm Hg. She has bilateral exophthalmos with exotropia of the right eye. Her visual acuity and extraocular movements are intact. The neck examination reveals a diffuse, nontender goiter, without nodules or thyroid bruits. The heart is tachycardic, intermittently irregular, and without murmurs. The lungs are clear to auscultation bilaterally. The abdomen is nondistended, soft, and nontender, with no palpable masses. There is no edema of the extremities. The neurologic examination reveals normal mentation, intact cranial nerves, intact motor strength and sensation, and normal reflexes. No tremor is noted.
The initial laboratory studies reveal complete blood count, electrolytes, renal function, and cardiac marker findings that are all within normal limits. A plain chest radiograph is interpreted as normal (not pictured). An electrocardiogram (ECG) is obtained (see Figure 1).

Ankylosing spondylitis

2009-07-08T02:59:00.000-07:00

Ankylosing spondylitis (AS) is a type of inflammatory arthritis that targets the joints of the spine. It
particularly affects the sacroiliac (SI) joint where the spine attaches to the pelvis. Symptoms
include back pain, stiffness and reduced mobility. Ankylosing spondylitis is also known as
rheumatoid spondylitis.

Ankylosing spondylitis is more common in Caucasians and affects twice as many men than women.
The condition usually appears between the ages of 14 and 40 years, while onset after the age of 40
is extremely rare. There is no cure for AS, but medical treatment and lifestyle habits such as
regular exercise can improve the person’s outlook.

Damage to the spine
The inflammation causes damage to the vertebrae (backbones). In response, the body grows more
bone tissue to repair the damage. Over time, this process builds abnormal bony outgrowths
(syndesmophytes) that knit together. This fusion of the vertebrae causes pain and reduces
mobility, especially in the lower back. About seven in 10 people with AS will develop some degree
of spinal fusion.

Causes
The exact cause of ankylosing spondylitis is unknown, but genes are thought to play a part.
Studies show that most people with AS have the gene called HLA-B27. Some HLA (human
lymphocyte antigen) genes suggest the person may be more likely to get autoimmune diseases.
Only one in 20 people with this gene develop ankylosing spondylitis. Since the presence of this
gene does not automatically lead to AS, other factors must be involved. Current theory suggests
that a person who has the gene variant must be exposed to certain environmental triggers in order
for the arthritis to develop. These triggers, however, are unknown.

Symptoms in children
In children, ankylosing spondylitis symptoms are commonly ignored or dismissed as ‘growing
pains’. The symptoms particular to children may include:
• Chronic pain in the back or neck
• Chronic pain in the knees, ankles or feet
• Swollen joints
• Increased stiffness after periods of inactivity
• Reduced pain and stiffness during and after exercise.

Symptoms in adults
Ankylosing spondylitis varies widely in its severity and progresses differently from one person to
the next. Generally speaking, the symptoms in adults may include:
• Chronic back pain, particularly in the lower back and hips
• Pain in other joints (such as the knee, shoulder or foot) or tendons (such as those at the
back of the heel or under the foot)
• Poor posture, since standing tall is uncomfortable or even painful
• Back stiffness
• Reduced mobility
• Difficulty standing up from a sitting position
• Difficulty walking
• Increased stiffness after periods of inactivity
• Reduced pain and stiffness during and after exercise
• Fatigue unrelieved by rest or sleep.

Other sites of inflammation
Ankylosing spondylitis
Ankylosing spondylitis may cause inflammation in other areas of the body, including:
• Tendon (enthesitis)
• Eye (uveitis or iritis)
• Bowel (colitis)
• Lung (fibrosis)
• Heart (aortitis).

Complications
Ankylosing spondylitis can cause a range of complications, including:
• Skeletal deformities such as a permanent stoop (in severe cases, the person may be
unable to lift their head from their chest)
• Total fusion of the spine (‘bamboo spine’)
• Increased susceptibility to bone fractures
• Fusion of the rib joints and associated breathing difficulties
• Lung lesions and recurrent lung infections
• Anaemia, as a result of chronic inflammation.

Diagnosis
Research suggests that ankylosing spondylitis may go undiagnosed for years, particularly in
children. It takes an average of seven years for an adult with ankylosing spondylitis to finally get a
diagnosis. This is unfortunate because early diagnosis and prompt treatment can improve the
person’s long-term outlook.
Tests used to diagnose AS may include:
• Medical history
• Physical examination
• X-ray
• Scanning procedures such as CT or MRI
• Blood test
• Genetic testing.

Treatment
There is no cure for ankylosing spondylitis. Medical treatment aims to manage pain, reduce the risk
of complications and improve quality of life. Options include:
• Non-steroidal anti-inflammatory medications (NSAIDs)
• Disease-modifying anti-rheumatic drugs (DMARDs)
• Corticosteroid medications
• Physical therapy, including exercises to improve flexibility and range of motion – either on
land or in the water
• In rare cases, surgery to repair badly damaged joints.

Self-help suggestions
Most people with ankylosing spondylitis develop some degree of spinal fusion. A key aim of
treatment is to encourage good posture so that the spine will fuse in an upright rather than
stooped position. Be guided by your doctor, but general self-help suggestions include:
• The most important management tool is regular exercise (including stretching), which
helps to keep the spine mobile and flexible. Ask your doctor or physiotherapist for further
information.
• Strong abdominal muscles contribute to good posture. Perform exercises to strengthen
your abdominal muscles as recommended by your doctor or physiotherapist.
• Pay careful and daily attention to posture. Remind yourself regularly to ‘stand tall’.
• If you tend to slump when seated, consider buying an ergonomic chair, lumbar support
cushion or other device. Ask your doctor or physiotherapist for recommendations.
• Avoid curling into a ball when in bed. Instead, try to lie straight, either on your back or
stomach.
• Don’t smoke.
Ankylosing spondylitis

Long-term outlook
Ankylosing spondylitis is a progressive disease, which means it tends to get worse over time.
Certain characteristics of AS suggest a poorer outlook, including:
• Earlier rather than later onset of symptoms
• Involvement of one or both sacroiliac joints
• Uveitis or iritis (inflammation of the eye)
• Cigarette smoking
• Sedentary lifestyle
• Failure to consistently manage the condition throughout life.

Things to remember
• Ankylosing spondylitis (AS) is a type of inflammatory arthritis that targets the joints of the
spine, particularly the sacroiliac (SI) joint where the spine attaches to the pelvis.
• There is no cure for AS – medical treatment aims to manage pain, reduce the risk of
complications and improve quality of life.
• The most important management tool is regular exercise (including stretching), which
helps to keep the spine mobile and flexible.

DIAGNOSIS OF CASE 3

2009-07-08T02:53:00.000-07:00

THE DIAGNOSIS OF CASE IS ANKYLOSING SPONDYLITIS.

Discussion

The anteroposterior and lateral radiographs of the spine demonstrated the classic "bamboo-spine" finding seen in cases of ankylosing spondylitis. The images showed sclerosis and ankylosis of the vertebral bodies, without loss of disc space. Bone formation extended across the anterior and lateral margins of the intervertebral disks of the lower thoracic and lumbar spine (syndesmophytosis). The sacroiliac joints showed extensive periarticular sclerosis and focal ankylosis.
Ankylosing spondylitis is a chronic inflammatory disorder of multiple articular and para-articular structures that principally involves the axial skeleton. It usually affects the sacroiliac joints and the spinal facet joints of the vertebrae. It sometimes involves the appendicular skeleton as well, such as the joints of the greater trochanter, patella, and calcaneum. Other extraspinal manifestations include iritis/uveitis and pulmonary involvement. The basic pathologic lesion of ankylosing spondylitis occurs at the entheses, which are sites at which ligaments, tendons, and joint capsules attach to bone. In the outer layers of the annulus fibrosis of the intervertebral disks, the condition manifests as a formation of new bone. The name of the disease is derived from Greek; "ankylos" means stiffening of a joint, and "spondylos" means vertebra. The disease is classified as a chronic and progressive form of seronegative arthritis. Ankylosing spondylitis affects men 4-10 times more frequently than women, and the symptoms generally appear in those aged 15-35 years. More than 90% of whites with ankylosing spondylitis have the HLA-B27 gene, but 6-8% of those with this gene do not develop the disease.[2,3]
Symptoms of ankylosing spondylitis include back pain and stiffness, peripheral joint and chest pain, sciatica, anorexia, weight loss, and low-grade fever. The back pain associated with this condition is typically transient at first, but it eventually becomes persistent. It is usually worse in the mornings and resolves with exercise. A typical patient may also complain of waking up with back pain at night. The pain is usually centered over the sacrum, but it may radiate to the groin, buttocks, and down the legs. With time, the back pain usually progresses up the spine and affects the rib cage, resulting in a restriction of chest expansion and diaphragmatic breathing (observed as ballooning of the abdomen during inspiration) as the costovertebral joints become affected. The cervical spine is ankylosed late in the course of the disease, leading to restriction in neck movement and head rotation. Without treatment, the spine eventually becomes completely rigid, with loss of the normal curvatures and movement.[2,3]
On physical examination, the loss of lateral flexion of the lumbar spine is the earliest objective sign of spinal involvement. The sacroiliitis may be detected by eliciting a tenderness response during percussion over the sacroiliac joints. Objective tests to quantify spinal restriction include touching the toes, the Schober test, and measurement of chest expansion. Additional physical findings include restriction of motion in the peripheral joints and tenderness over the enthuses. The physical exam should also include evaluation for signs of potentially serious cardiovascular and pulmonary complications, such as aortic incompetence secondary to aortitis, conduction defects of the heart, cardiomyopathy, pericarditis, apical fibrosis of the lungs, bronchiectasis, cavitation of the chest, and development of a restrictive ventilatory pattern. Other associated conditions include the development of inflammatory bowel disease, uveitis (in up to 20% of patients), radiculitis secondary to inflamed nerves, and, rarely, amyloidosis.[2,3]
Specific criteria for the diagnosis of ankylosing spondylitis include the Rome criteria (developed in 1963) and the New York criteria (developed in 1968). Although these criteria have been generally accepted as useful, limitations are recognized and overlaps exist among the clinical and radiologic features of various seronegative spondyloarthropathies. Sacroiliitis is the hallmark of ankylosing spondylitis and is a requisite for the diagnosis under both sets of criteria. Other conditions, such as psoriasis, Reiter disease, enteropathic arthropathy, hyperparathyroidism, and osteitis condensans ilii, may also result in bilateral symmetric sacroiliac joint disease and should be considered in the differential diagnosis. Ankylosing spondylitis may also present with asymmetric sacroiliitis, which may be more characteristic of other conditions, such as psoriasis, Reiter disease, rheumatoid arthritis, and gouty arthritis. Radiographically, diffuse idiopathic skeletal hyperostosis (DISH) has a similar appearance to ankylosing spondylitis; however, DISH typically occurs at a later age and does not involve the sacroiliac joint.[2,3]
The radiographic changes usually first appear in the sacroiliac joints, followed by the thoracolumbar and lumbosacral spine; this is in line with the natural progression of the disease. The disease then proceeds cephalad up the spine; however, the cervical spine may also be affected without involvement of the thoracic or lumbar spine. Radiographically evident peripheral-joint abnormalities are seen in more than 50% of patients. Abnormalities can also be seen in the symphysis pubis and in the manubriosternal, sternoclavicular, and temporomandibular joints. Spinal findings include osteitis, syndesmophytosis, diskovertebral erosions and destruction (Romanus lesions), and disk calcification. Radiographically, joint involvement appears as joint-space narrowing, periostitis, osseous erosion, and minimal periarticular osteoporosis (less than that seen with rheumatoid arthritis). Sacroiliac joint involvement is usually bilateral and symmetric.[1,3]
Common laboratory findings are an elevated erythrocyte sedimentation rate (during the acute phase), a positive HLA-B27 histocompatibility antigen, mild leukocytosis, normochromic normocytic anemia (anemia of chronic disease), and negative results for rheumatoid factor.[2,3]
The general principles of managing chronic arthritis also apply to ankylosing spondylitis. Among the various nonsteroidal anti-inflammatory drugs (NSAIDs) available to treat the disease, indomethacin may be the most effective. The lowest dose that provides pain relief should be used in order to avoid potentially serious complications, such as gastritis, peptic ulcer disease, and renal insufficiency. Sulfasalazine can be useful if peripheral arthritis is substantial, but it may be less effective when spinal and sacroiliac pain are the most prominent symptoms. In the majority of patients, the symptoms persist for life, although in some cases remission does occur.[5]
Physical therapy and exercise can help prevent axial immobility. Specifically, spinal extension and deep-breathing exercises maintain spinal mobility, encourage erect posture, and promote chest expansion. Maintaining an erect posture and sleeping on a firm mattress with a thin pillow can help reduce thoracic kyphosis. Severe hip or spinal involvement may require surgical repair. Antitumor necrosis factor (anti-TNF) agents, such as infliximab and etanercept, are relatively new but often very effective therapeutic agents that may be considered for patients with pain refractory to other interventions.[4,5]
The patient in this case was started by his primary care provider on a low dose of indomethacin to reduce pain and decrease inflammation. He was referred by the primary care provider to a rheumatologist for further evaluation and management and ongoing medical treatment. He was also referred to a physical therapist to begin a proper exercise and stretching program. Information regarding support groups to provide further education on the disease process and available treatment options were also given to the patient.

CASE 3 Young Man With Lower Back Pain and Low-Grade Fever Background

2009-07-01T07:48:00.000-07:00

A Young Man With Lower Back Pain and Low-Grade Fever
Background

A 19-year-old man presents to his primary care provider with a 2-month history of lower back pain and stiffness. The pain is intermittent, achy, and usually worse in the morning than it is later in the day or evening. He has also noticed a progressive inability to perform activities that require flexibility in the back, such as bending down to pull on his pants or tying his shoelaces. The pain sometimes awakens him at night. It is improved with exercise. He also reports a several-month history of low-grade fever, malaise, and anorexia, as well as an unintended weight loss of 10 lb (4.5 kg). He has not noted any masses on his testicles with self-examination. The patient has no history of rash. He does not have any known chronic medical conditions. He takes one multivitamin per day. He has never smoked, but he does drink an occasional glass of wine with dinner. There is no significant family history of disease.

On physical examination, the patient has a blood pressure of 125/67 mm Hg and a heart rate of 60 bpm. His respiratory rate is 8 breaths/min and his temperature is normal at 98.0°F (36.7°C). The cardiovascular and respiratory portions of the examination are normal; specifically, no murmurs or rubs are detected. The patient has no photophobia, eye redness, or decreased visual acuity. On examination of the back, flexion of the lumbar spine is clearly decreased when the patient attempts to bend down to touch his toes. He also has pain and limited range of motion with rotation and lateral flexion at the lumbar spine. His chest expansion is mildly diminished. The remainder of the physical examination is within normal limits.
As part of the initial workup of the findings on physical examination, routine laboratory investigations, including a complete blood cell (CBC) count and a basic electrolyte panel, as well as plain radiographs of the back, are performed. The chemistry panel is unremarkable, and the CBC reveals a white blood cell (WBC) count of 4.6 × 103/μL (4.6 × 109/L), a hemoglobin of 13.7 g/dL (137 g/L), a hematocrit of 43% (0.43), and a platelet count of 120 × 103/μL (120 × 109/L). The electrolytes are within normal limits. A rheumatoid factor test is negative, and the erythrocyte sedimentation rate is 64 mm/hr (normal range, <10 mm/hr for men). The patient has a positive finding for human leukocyte antigen (HLA)–B27.
Anteroposterior and lateral radiographs of the lumbar spine are obtained (see Figure 1).

What is the underlying disease process for the radiographic abnormalities?

Hint: The spine and sacroiliac joints show classic findings for the diagnosis.

Ankylosing spondylitis

Spinal stenosis

Psoriatic arthritis

Diffuse idiopathic skeletal hyperostosis

DIAGNOSIS OF CASE 2

2009-06-28T05:14:00.000-07:00

Discussion

The axial images of the CT urograph, as well as the associated sagittal reformation, demonstrated a large filling defect in the right renal pelvis. The filling defect extended into and replaced most of the right renal pelvis, resulting in a mass effect and a relative delay in the kidney's enhancement during the nephrographic phase (Figures 2-3). The combination of this radiographic appearance with a history of painless hematuria and positive urine cytology was indicative of upper-tract urothelial carcinoma.
Upper-tract urothelial carcinoma refers to malignant changes of the urothelial cells lining the urinary tract from the renal calyces to the ureteral orifice. Upper urinary tract urothelial carcinomas are relatively uncommon, only accounting for about 5-7% of all renal tumors and about 5% of all urothelial tumors. It appears that the true incidence of upper-tract tumors is increasing as the population ages. Upper-tract cancer is typically seen at an older age than bladder cancer; it rarely presents before the age of 40 years, and it has an average age of presentation of 65 years. The incidence of upper-tract tumors is 10 cases per 100,000 population per year. The highest incidence, however, appears to occur in Balkan countries, where urothelial cancers represent 40% of all renal cancers. The likelihood of developing upper-tract tumors among men is about twice that of women. Whites have a 2:1 risk of developing upper-tract tumors when compared with blacks; however, data indicates that disease-specific annual mortality is greater in black men than in white men (7.4% versus 4.9%) and greater in women than in men (6.1% versus 4.4%). Proposed etiologies for developing upper-tract urothelial carcinoma are similar to that of bladder cancer and include environmental factors (cigarette smoking), occupational exposures (aniline dyes), and treatment with anti-inflammatory (phenacetin) or chemotherapy (cyclophosphamide, ifosfamide) agents. A familial association has been identified in patients with Balkan nephropathy, although an unidentified environmental trigger may be the underlying etiology in these cases.[1,2,4]
The most common presenting symptom or finding that leads to the diagnosis of upper-tract urothelial tumors is hematuria, which occurs in 56-98% of patients. The second most common symptom is flank pain, which occurs in 30% of cases. The pain may vary from a dull sensation resulting from gradual obstruction of the collecting system to an acute pain mimicking renal colic, believed to result from an acute obstruction by a thrombus. About 15% of patients are asymptomatic at presentation and are diagnosed incidentally by an imaging study performed for a different indication. Patients presenting with advanced disease may suffer from loss of appetite, weight loss, a flank or abdominal mass, and bone pain. Traditionally, intravenous pyelography (IVP) was used to diagnose upper-tract tumors; however, CT urography (CT with a delayed urographic phase) is now becoming the primary diagnostic modality. Using CT urography, the sensitivity for detecting upper-tract malignant disease has been reported to approach 100%, with a specificity of 60% and a negative predictive value of 100%. CT urography does, however, expose the patient to higher doses of radiation and requires intravenous administration of contrast material. Radiolucent filling defects, obstruction or incomplete filling of a part of the upper tract, and nonvisualization of the collecting system are the typical findings suggestive of an upper-tract tumor. Filling defects may represent stones, blood clots, external compression, or a fungus ball. Stones can be ruled out by detecting calcifications on renal ultrasonography or a noncontrast CT scan. The clinician should always asses the contralateral kidney for possible bilaterality and to determine its functioning.[1,2]
If the diagnosis remains in question or the treatment plan may be adjusted based on a ureteroscopic evaluation, endoscopy with or without biopsy should be performed. Ureteroscopy provides a valuable tool in the evaluation of upper-tract urothelial carcinoma. As a result of advancements in optics, flexible ureteroscopes and endoscopic equipment, visualization and sampling of the tumor have improved. The greatest prognostic factors in the management of upper-tract urothelial carcinoma are pathologic grade and stage. Histologic correlations of up to 90% have been established between the initial ureteroscopic biopsy and the final pathologic specimen; however, because of the small size of the biopsy specimen and the depth of tissue sampling, outcomes with tumor stage have not demonstrated such a strong correlation. In 40 urothelial tumors staged in one series, 45% of tumors thought to be pathologic Ta were upstaged to T1-T3 at the time of complete resection. Ureteroscopic biopsy cannot reliably predict tumor stage; therefore, a combination of tumor grade, endoscopic visual appearance of the tumor, and radiologic appearance are required for the best prediction of tumor stage.[1,2,4]
Because voided urine cytology is nonspecific, the usefulness of it is limited. Even when using selectively obtained ureteral cytologies, the diagnostic yield is still only 60% accurate. Improved diagnostic yield has been demonstrated with the use of saline washing or brush biopsy, with an approximate sensitivity of 90% and a specificity near 90%.[2]
The standard treatment for upper-tract urothelial carcinoma has been nephroureterectomy with excision of a cuff of bladder. Advancements in percutaneous and endoscopic techniques, however, have allowed more conservative nephron-sparing procedures for patients with solitary kidneys or those who are otherwise not ideal candidates for extirpative surgery. Considered the "gold standard", radical nephroureterectomy with resection of a bladder cuff is the treatment of choice for large, high-grade, single or multifocal, noninvasive or invasive renal pelvis or proximal ureter tumors. The risk for multifocality and a high incidence of ipsilateral recurrence following partial resection are the reasons for the preference of this radical approach. Several approaches may be used, including totally open, totally laparoscopic, or a combination of both (eg, laparoscopic nephroureterectomy combined with an open distal intramural ureteral resection).[1,2,3,4]
Patients with a solitary kidney, bilateral disease, renal failure, or significant comorbidities preventing a large abdominal surgery are candidates for endoscopic resection. An additional group of patients who may benefit from endoscopic treatment are those with a small, low-grade lesions in the presence of a normal contralateral kidney. Tumors located at the distal ureter may be treated with a rigid ureteroscope, whereas those situated in the upper-urinary tract may be reached by a flexible ureteroscope or by an antegrade percutaneous approach. Initially, biopsies are taken, and then ablation is achieved using electrocautery or laser energy. Historically, open nephron-sparing surgery for upper-tract urothelial carcinoma was used in patients with a large renal pelvis tumor in a solitary kidney or in cases of synchronous bilateral tumors. Advancements in endourologic techniques, particularly percutaneous antegrade renal surgery, have largely replaced this approach for the conservative management of renal pelvis tumors. Segmental (partial) ureteral resection with end-to-end anastomosis or bladder reimplantation is performed in cases with low-grade, noninvasive tumors of the proximal or mid ureter that cannot be managed endoscopically when nephron-sparing is crucial for the preservation of renal function.[1,2,4]
The recurrence pattern following treatment of upper-tract urothelial carcinoma may be divided into vesical and extravesical recurrence. The higher the grade and stage of the upper-tract urothelial carcinoma, the higher the risk for extravesical recurrence. The recommended follow-up for patients treated for upper-tract urothelial carcinoma should consist of periodic history and physical examination, urinary cytology, and surveillance cystoscopy (occurring every 3 months for the first 2 years after treatment, every 6 months for the next 2 years, and yearly thereafter if the patient is free from disease recurrence). In cases of high-grade urothelial carcinoma, radiographic studies, including chest radiography and abdominopelvic CT scanning, should be performed every 6 months for the first 2 years and then yearly thereafter. Ipsilateral endoscopy for patients who undergo organ-sparing treatment should occur every 6 months for the first 2-3 years and then yearly thereafter, provided that the patient is free of disease. Bone scans should only be performed if the patient has symptoms of bone pain or for an elevated alkaline phosphatase level.[1,4,5]
In this patient, a cystoscopy was performed upon admission which showed a normal bladder without any exophytic tumor. The combination of a large filling defect in the right renal pelvis seen on CT urography and positive urine cytology made the diagnosis of upper-tract urothelial carcinoma. The patient received a comprehensive explanation of the available treatment modalities and elected to undergo nephroureterectomy. The surgery involved a combined laparoscopic and open approach. The right kidney and ureter were removed entirely, including a bladder cuff around the right distal ureter. The postoperative phase was uneventful and the patient was discharged on the seventh postoperative day. She is now under surveillance after surgery, with no evidence of recurrence.

CASE 2 Painless Bloody Urination in a 60-Year Old Woman

2009-06-20T18:57:00.000-07:00

A 60-year-old woman is referred to the emergency department (ED) because of a recent event of painless macroscopic hematuria. She reports having experienced several similar episodes during the past year, all of which resolved spontaneously. She regards these episodes as being of gynecologic origin because she is 5 years postmenopausal. She describes a general feeling of malaise in the days preceding the current episode, but she denies having any fever, dysuria, or increased frequency or urgency of urination. The patient also describes an unintentional weight loss of 11 lb (5 kg) during the past 2 years. The patient's previous medical history includes hypothyroidism that was treated medically with thyroxine, and her surgical history includes 2 treatments of dilatation and curettage (D&C) and a tonsillectomy. She has no known drug or food allergies, and she denies smoking, drug use, or alcohol consumption. She has no previous history of kidney stones or recurrent urinary tract infections.
On physical examination, the patient appears well. She has a temperature of 98.8°F (37.1°C), a pulse rate of 71 bpm, and a blood pressure of 150/86 mm Hg. The head and neck examination is normal. Lung auscultation reveals normal breath sounds bilaterally, without wheezing or crackles. Her heart sounds are regular, with a 2/6 systolic murmur maximally auscultated over the right second intercostal space. The abdomen is nondistended and nontender, no masses are palpated, and there are no signs of peritoneal irritation. No peripheral edema is noticed, peripheral pulses are palpated, and the neurologic examination is normal. A gynecologic evaluation that includes a speculum examination and transvaginal ultrasonography is performed, which reveals no pathologic findings.
A laboratory analysis, including a complete blood cell (CBC) count, coagulation studies, and a basic metabolic panel, shows a normal hemoglobin level, normal platelet count, and no coagulopathy. No electrolyte abnormalities are present. A urine dipstick test shows no signs of hematuria, and a urine culture is negative. Urine cytology is positive for malignant cells. Cystoscopy is performed, which demonstrates a normal urethra leading to a urinary bladder covered by normal mucosa, with no exophytic lesions and no active bleeding. A computed tomography (CT) examination of the abdomen and pelvis with intravenous contrast is obtained (see Figure 1).

FIGURE 1

CRYOGLOBUNEMIA

2009-06-20T18:46:00.000-07:00

Definition
Cryoglobulinemia is the presence of abnormal proteins in the blood. These abnormal proteins become thick or gel-like in cold temperatures.

Causes
Cryoglobulins are antibodies. It is not yet known why they become solid at low temperatures. When they do thicken or become somewhat gel-like, they can block blood vessels throughout the body. This may lead to complications ranging from skin rashes to kidney failure.

Cryoglobulinemia is part of a group of diseases that cause vasculitis -- damage and inflammation of the blood vessels throughout the body. The disorder is grouped into three main types, depending on the type of antibody that is produced:
• Cryoglobulinemia type I
• Cryoglobulinemia typeII
• Cryoglobulinemia type III
Types II and III are also referred to as mixed cryoglobulinemia.
Type I cryoglobulinemia is most often related to cancer of the blood or immune systems.
Types II and III are most often found in people who have a chronic (long-lasting) inflammatory condition, such as an autoimmune disease or hepatitis C. Most patients with mixed cryoglobulinemia have a chronic hepatitis C infection.
Other conditions that may be related to cryoglobulinemia include:
• Leukemia
• Multiple myeloma
• Mycoplasma pneumonia
• Primary macroglobulinemia
• Rheumatoid arthritis
• Systemic lupus erythematosus

Symptoms
Symptoms vary depending on the type of cryoglobulinemia and the organs that are affected. In general, symptoms may include:
• Difficulty breathing
• Fatigue
• Glomerulonephritis
• Joint pain
• Muscle pain
• Purpura
• Raynaud's phenomenon
• Skin death
• Skin ulceration

Exams and Tests
The doctor will perform a physical exam. There may be signs of liver and spleen swelling.
Tests for cryoglobulinemia include:
• Complete blood count (CBC)
• Complement assay -- numbers will be low
• Cryoglobulin test -- may show presence of cryoglobulins
• Liver function tests -- may be high
• Rheumatoid factor -- positive in types II and III
• Skin biopsy
• Urinalysis -- may show blood in the urine if the kidneys are affected

Other tests may include:
• Angiogram
• Chest x-ray
• ESR
• Hepatitis C test
• Nerve conduction tests, if the person has weakness in the arms or legs
• Protein electrophoresis - blood

Treatment
Treatment of mild or moderate cryoglobulinemia depends on the underlying cause. Treating the cause will often treat the cryoglobulinemia.
Mild cases can be treated by avoiding cold temperatures.
Standard hepatitis C treatments usually work for patients who have hepatitis C and mild or moderate cryoglobulinemia. However, the condition can return when treatment stops.
Severe cryoglobulinemia (involves vital organs or large areas of skin) is treated with corticosteroids and other medications that suppress the immune system.
Treatment may also involve plasmapheresis. Plasmapheresis is a procedure in which blood plasma is removed from the circulation and replaced by fluid, protein, or donated plasma.

Outlook (Prognosis)
Cryoglobulinemia is not usually deadly. However, if the kidneys are affected, the outlook is poor.

Possible Complications
Complications include:
• Bleeding in the digestive tract (rare)
• Heart disease (rare)
• Infections of ulcers
• Kidney failure
• Liver failure
• Skin death
• Death

Prevention
There is no known prevention. Avoiding exposure to cold temperatures may prevent some symptoms.
Because so many cases of mixed cryoglobulinemia are associated with hepatitis C, prevention of hepatitis C infection may reduce your risk of cryoglobulinemia.

diagnosis of case 1

2009-06-20T18:43:00.000-07:00

Given the patient's history of immunoproliferative disorder, and the atypical presentation of her lesions, consideration was given to a vasculitic or vasculopathic etiology. A panel of additional laboratory studies was sent. Lupus anticoagulant was not detected, and anticardiolipin was also negative. Antinuclear antibodies (ANA) and antibodies to neutrophil cytoplasmic antigens (ANCA) were not detected. All hepatitis markers were negative, including for hepatitis C. The test for rheumatoid factor was negative. The cryoglobulin test was positive, and quantified as primarily immunoglobulin G (IgG). This was subsequently confirmed on a separate test several months later.

Cryoglobulins are single or mixed immunoglobulins that reversibly precipitate at low temperatures. Cryoglobulinemia is defined as the presence of cryoglobulins in the serum. This can lead to a syndrome of systemic inflammation caused by immune complexes associated with the cryoglobulins. The mechanism of precipitation is poorly understood. The solubility of cryoglobulins is partially related to the structure of the immunoglobulin heavy and light chains. Alteration in protein conformation resulting from temperature changes may cause decreased solubility and subsequent vasculitic damage. The ratio of antibody to antigen in circulating cryoglobulin aggregates affects the rate of clearance from the circulation and the resultant location of tissue deposition.[2,4]

Cryoglobulins are reported in otherwise healthy individuals, so their true prevalence is unknown. While cryoglobulinemia is thought to be rare, it may be underdiagnosed because of the diversity of clinical presentations. The prevalence of mixed cryoglobulinemia is approximately 1:100,000. The female-to-male ratio is 3:1. The mean age reported is 42-52 years.

Cryoglobulinemia is classified based on cryoglobulin type using the Brouet classification. Type I cryoglobulinemia is monoclonal, usually immunoglobulin M (IgM). Types II and III are immunocomplexes formed by monoclonal or polyclonal IgM, respectively. Types II and III have rheumatoid factor (RF) activity and bind to polyclonal immunoglobulins. These two types are referred to as "mixed cryoglobulinemia". Type I accounts for 10-15% of cases, type II is seen in 50-60%, and type 3 is found in 25-30%. Atypical cryoglobulins with a microheterogeneous composition that does not fit into any of the classifications have prompted suggestion of a classification called Type II-III variant.[2,3,4]

Type I cryoglobulinemia is usually related to an underlying lymphoproliferative disease and may be difficult to distinguish from Waldenström macroglobulinemia, multiple myeloma, or chronic lymphocytic leukemia. Type I cryoglobulinemia may result in hyperviscosity as a result of high levels of circulating monoclonal cryoglobulins, leading to physical obstruction of vessels. In addition, immune complex deposition may cause an inflammatory vasculitis. Specific clinical manifestations include acrocyanosis, retinal hemorrhage, Raynaud phenomenon with digital ulceration, livedo reticularis, purpura, and arterial thrombosis.[1,2,3,4]

Types II and III cryoglobulinemia are associated with chronic inflammatory states, such as systemic lupus erythematosus, Sjögren syndrome, and viral infections (particularly hepatitis C). B-cell clonal expansion, particularly RF-secreting cells, is a distinctive feature in many of these disease states. Tissue damage results from immune complex deposition and complement activation. Specific clinical manifestations associated with types II and III cryoglobulinemia include arthralgia (usually of the leg, ankle and foot), fatigue, myalgia, renal immune-complex disease, cutaneous vasculitis, and peripheral neuropathy. The Meltzer triad of purpura, arthralgia, and weakness is seen in 25-30% of patients.[1,2,4,5]

Mortality and morbidity in individuals with cryoglobulinemia often depends on the underlying associated disease, if present. The overall prognosis is worse in patients with associated disease. The mean survival is approximately 50% at 10 years after diagnosis. The risk of renal failure appears to be greater in those with hepatitis C virus—associated disease.[2,4]

Lymphoproliferative disease is more common in individuals with cryoglobulinemia. Patients with mixed cryoglobulinemia may develop benign lymphoid infiltrates in the spleen and bone marrow. Less frequently, patients may develop B-cell non-Hodgkin lymphoma. The incidence of malignant lymphoma in mixed cryoglobulinemia varies from 10-40%, with an onset of 5-10 years after disease diagnosis.[2,3]

Cutaneous manifestations are almost always present in cryoglobulinemia. Lesions are most often seen in dependent areas (especially the lower extremities), and they include erythematous macules and purpuric papules (90-95%), as well as ulcers (10-25%). Lesions in nondependent areas (head and mucosa) are more common in type I cryoglobulinemia, as are livedo reticularis, Raynaud phenomenon, and ulcers. Nail fold capillary abnormalities are common and include dilatation, altered orientation, capillary shortening, and neoangiogenesis.[1,3]

Renal disease may occur secondary to thrombosis (type I cryoglobulinemia) or immune complex deposition (types II and III). The incidence of renal disease varies from 5-60%. Histologically, membranoproliferative glomerulonephritis is almost always seen in mixed cryoglobulinemia. Renal involvement is one of the most serious complications of cryoglobulinemia, and it typically manifests early in the course of the disease (within 3-5 years of diagnosis). This may progress to complete renal failure. Hypertension and nephritic-range proteinuria with resultant edema are characteristically seen in cryoglobulinemia.[2,4]

A reduction in forced expiratory flow rates and the presence of interstitial infiltrates are common in mixed cryoglobulinemia. Approximately 40-50% of patients are symptomatic, with dyspnea, cough, or pleuritic pain. Severe pulmonary disease is rare. Neuropathy is common in types II and III disease, affecting 70-80% of patients. Sensory neuropathy is more common than motor neuropathy (5% of patients). Abdominal pain has been reported in 2-22% of patients. Vasculitis of the small mesenteric vessels that leads to acute abdomen has been reported. Splenomegaly may be seen in these patients.

The differential diagnosis of cryoglobulinemia includes antiphospholipid syndrome, chronic lymphocytic leukemia, Churg-Strauss syndrome, cirrhosis, giant cell arteritis, glomerulonephritis, Goodpasture syndrome, hemolytic-uremic syndrome, hepatitides, non-Hodgkin lymphoma, microscopic polyangiitis, multiple myeloma, polyarteritis nodosa, sarcoidosis, serum sickness, systemic lupus erythematosus, and Waldenström hypergammaglobulinemia.[2,3]

Key lab studies include evaluation for serum cryoglobulins. The specimen must be obtained in warm tubes (98.6°F or 37°C) without anticoagulants and then allowed to clot before centrifugation. The serum is then incubated at 39.2°F (4°C). Type I tends to precipitate within 24 hours. Type III may require 7 days to precipitate. Specific immunologic assays may be used to identify cryoglobulin components (immunoglobulins, light chains, clonality).

Urinalysis, serum creatinine, and electrolytes are important to evaluate for evidence of renal disease. A complete blood cell (CBC) count should be done to screen for infection, anemia, or leukemia. Abnormal liver function studies and transaminases may suggest underlying hepatitis. If so, hepatitis serologies are indicated. If hepatitis C virus test results are negative and clinical suspicion remains high, serologies may be performed on the cryoprecipitate. Rheumatoid factor is positive in types II and III. ANA is indicated upon clinical suspicion of underlying connective-tissue disease. ESR elevation is nonspecific, and it may occur in the presence of a number of associated inflammatory disorders. Patients may display hypocomplementemia (especially low C4 levels). The clinician should consider serum protein electrophoresis, urine protein electrophoresis, and quantitative immunoglobulin if there is suspicion for underlying gammopathy.[3]

Clinical imaging should be ordered as warranted based on suspected underlying disease. Tissue biopsy may be required for diagnosis in patients with vasculitis and/or renal disease. Purpura is characterized by dermal vasculitis that extends variably to the subcutaneous tissue. Hepatitis C virus—associated proteins have been found in vasculitic skin biopsy specimens. Although samples generally exhibit inflammatory vascular changes, intraluminal cryoglobulin deposits may be observed, especially in renal glomeruli.

The management of cryoglobulinemia should be focused on treating underlying conditions, as well as limiting the precipitation of cryoglobulins and the resultant inflammatory effects. Asymptomatic cryoglobulinemia does not require treatment. When treatment is required, it is based on suppression of the immune response.[2]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in patients with arthralgia and fatigue, but may be contraindicated in patients with renal disease. Immunosuppressive medications (eg, corticosteroids, cyclophosphamide, azathioprine) are indicated in cases with evidence of organ involvement, such as vasculitis, renal disease, progressive neurologic findings, or severe skin manifestations.[2]

Plasmapheresis is indicated for severe or life-threatening complications related to in vivo cryoprecipitation or serum hyperviscosity. Concomitant use of high-dose corticosteroids and cytotoxic agents is recommended for the reduction of immunoglobulin production.[2]

Pegylated interferon alfa combined with ribavirin has been demonstrated to be effective in patients with cryoglobulinemia associated with hepatitis C, and efficacy in patients with chronic myelogenous leukemias and low-grade lymphomas has been reported.

Rituximab (anti-CD20 chimeric monoclonal antibody) has shown promise in controlling vasculitis, peripheral neuropathy, arthralgias, low-grade B-cell lymphomas, renal disease, and fever, specifically in patients with hepatitis C virus—related mixed cryoglobulinemia refractory to or unsuitable for corticosteroids and antiviral therapy. Studies have not yet been published on its efficacy and safety in the setting of other types of cryoglobulinemia.[2,4]

The patient in this case was referred to rheumatology and prescribed a course of oral corticosteroids. She was also referred to dermatology and had azathioprine added to her treatment. The lesions began to slowly shrink and lift at the edges (see Figure 2). Serial debridements were performed. Appropriate wound care was provided by her caregiver under instruction and supervision of the wound center. Following this care plan, the patient has had nearly complete resolution of most of her lesions (see Figure 3). She developed a persistent pancytopenia despite discontinuation of the azathioprine. She was referred to a hematologist and now has evidence of multiple myeloma based on bone marrow biopsy, with continued positive cryoglobulins.

Necrotic Skin Lesions in a 61-Year-Old Woman

2009-06-15T18:38:00.000-07:00

A 61-year-old woman presents to the wound center for continued treatment of venous leg ulcers complicated by diabetes mellitus. Her past medical history is remarkable for essential hypertension and obesity. The patient also has a history of angioimmunoblastic lymphadenopathy, which occurred over 15 years ago. The patient can not remember any details of this diagnosis; consultation with her primary care clinician reveals that this was a benign/peripheral presentation. No records are available for review. According to the primary care clinician, the condition went into complete remission following a course of prednisone. The patient notes that she has developed new wounds on both of her thighs. The lesions are black, with surrounding redness and tenderness. There is no itching. She states that the lesions have been enlarging slowly over the past several days, and many are now several centimeters in diameter. She denies having any fever or chills. Her fasting serum glucose readings have been stable in the 100-200 mg/dL (5.55-11.1 mmol/L) range. She denies experiencing any easy bruising or bleeding. She has not had any recent trauma or procedures in the area of the lesions, and she has not had any recent changes in her medications. She has no history of smoking, alcohol or illicit drug use.

On physical examination, her oral temperature is 97.8°F (36.6°C). Her pulse is 86 bpm and regular, and her blood pressure is 128/81 mm Hg. Her respiratory rate is 14 breaths/min. She is in no acute distress, but she does note that the wounds are causing her discomfort. The examination of her head, neck, lungs, heart and abdomen is unremarkable. The skin of the upper extremities and torso is also unremarkable. She has a nonhealing venous ulcer on each of her medial malleolar areas, which are unchanged from previous examination. She has multiple black eschars on her thighs, each surrounded by a centimeter of erythema with a slightly reticular pattern, as well as induration. She has trace edema to her ankles, but no edema in her legs or thighs. The lesions are tender. There are no vesicles or pustules. No confluent or ascending erythema is noted. The largest lesion measures 4.4 × 2.6 cm (see Figure 1).

Laboratory testing shows a white blood cell (WBC) count of 10.1 × 103/µL (10.1 × 109/L; normal range, 4.1- 10.9 × 103/µL), a hemoglobin of 10 g/dL (100 g/L; normal range, 12.0-15.2 g/dL), platelets of 492 × 103/µL (492 × 109/L; normal range, 140-450 × 103/µL), and a normal WBC differential. The basic metabolic panel is normal. The hemoglobin A1c finding is 6.6% (0.066; normal range, 3.8-6.4%). The albumin is normal at 3.5 g/dL (35 g/L), and the erythrocyte sedimentation rate (ESR) is elevated at 80 mm/hr (normal range, 1-25 mm/hr).

Biopsies are obtained of representative lesions at their edges. They demonstrate acute and chronic inflammation in the dermis and subcutaneous fat. No viral cytopathic changes are seen. Small vessel microthrombi are limited to the base of the ulcer and are not identified in vessels away from the ulcer, which suggests a secondary thrombotic reaction. No specific changes of vasculitis or malignancy are identified.

What is the diagnosis?

Hint: Her current diagnosis is associated with her remote past medical history.

Multiple myeloma

Cryoglobulinemia

Non-Hodgkin lymphoma

Giant cell arteritis