Repro test 3: ppt 8 & 9

Pregnancy Physiology

• Pregnancy changes physiology, including pathophysiology.
• Most changes are hormonally driven and affect multiple organ systems.
• Hormones involved: progesterone, estrogen, renin, aldosterone, cortisol, insulin.
• Some changes are driven by anatomical changes, primarily due to the uterus.
• Most changes aim to optimize fetal development and prepare for delivery, focusing on oxygen and nutrient delivery.

Placenta

• The placenta is a specialized organ crucial for oxygen and nutrient delivery to the fetus.
• Weighs 500 grams (1 pound) at birth
• It prevents the fetus from being recognized as foreign by the mother's immune system.
• Maternal blood flow interacts with fetal umbilical capillaries in pockets called lacunae.
• The placenta acts as a low-resistance "sink" for maternal blood flow.

Placental Barrier

• Allows the passage of certain materials via passive diffusion.
• Mostly large proteins and cells cannot pass.
• IgG, responsible for maternal immunity, crosses the placenta.

Placental Metabolic Activity

• In the third trimester, the placenta receives 20-25% of cardiac output, about 750 ml/min.
• The placenta's high metabolic activity requires significant oxygen, equal to the fetus's needs.
• The placenta is refractory to vasoactive medications.

Corticotropin Releasing Hormone

• The placenta maintains high ACTH and cortisol levels.
• ACTH release causes POMC (pigmentation hormone) release, leading to skin darkening during pregnancy.
• POMC contributes to linea nigra and melasma.

Cardiovascular and Hematologic Changes

• Vascular tone decreases, leading to vasorelaxation.
• Systemic vascular resistance (SVR) decreases by 20% due to the low resistance of the placenta.
• Vena cava compression can occur due to positional effects.
• Blood volume increases by 50-100%.
• Red blood cell (RBC) mass increases by 25-40%.
• Physiological dilution results in relative anemia.

Cardiac Changes

• Cardiac output (CO) increases significantly due to increased stroke volume (SV) and heart rate (HR).
• Cardiac axis is displaced cephalad and left.
• Point of maximal impulse (PMI) is lateral and elevated.
• Altered thoracic dimensions lead to left axis deviation.
• Murmurs are common in over 96% of pregnant women due to increased blood volume flowing through valves.
• Virtually all valves can be affected, especially the aortic and pulmonary valves.
• Resting heart rate is increased (80s instead of 70s, reaching 100s with minimal exertion).
• Ventricular distention increases by 25%.
• Cardiomyopathy can occur during pregnancy; don't assume it's solely a physiological change.
• Non-specific ST and T wave changes and increased dysrhythmias are common.
• Physiological hypokalemia, due to increased mineralocorticoid activity, may contribute to dysrhythmias.
• Left ventricular hypertrophy (LVH) and mild pericardial effusion are common.

Blood Pressure Changes

• Blood pressure decreases in the second trimester.
• It returns to baseline by the end of pregnancy.
• Hypertensive disorders of pregnancy are frequent, usually starting towards the end of pregnancy.
• Cardiac adaptations: CO up, SVR down, HR up.

Signs and Symptoms Mimicking Heart Disease

• Clinical signs: peripheral edema and jugular venous distension (JVD).
• Symptoms: reduced exercise tolerance and dyspnea.
• Auscultation: S3 gallop and systolic ejection murmur.
• Chest X-ray: change in heart position and size, increased vascular markings.
• Electrocardiogram (EKG): non-specific ST-T wave changes, axis deviation, LVH.
• Echocardiogram: mild pericardial effusion.

Anatomical Considerations

• Uterine position progresses: pelvic brim by 12 weeks, umbilicus by 20 weeks.
• Uterine compression affects: bladder (frequency), ureters (hydroureter), SI joint, pubic symphysis (pain).

Elevated Renin

• Progesterone stimulates renin production, also produced by the placenta.
• Consequences: increased sodium absorption, increased potassium excretion, water retention (6-8 L).

Renal Changes

• Increased renal blood flow due to expanded blood volume.
• 50-75% increase in renal workload.
• Glomerular filtration rate (GFR) increases by 50%.
• Diluted plasma proteins like albumin lead to a lower colloid osmotic pressure.

Other Urinary Tract Changes

• Ureteral dilation (hydroureter): progesterone leads to decreased ureteral peristalsis, exacerbated by uterine obstruction.
• Urinary stasis increases ureteral dilation and the risk of ascending bladder infections (pyelonephritis).
• Dilation of the renal pelvis and calyces.
• Increased kidney size.

Lung and Respiratory Adaptations

• Respiratory rate does not change significantly.
• Thoracic diameter increases by 2 cm, circumference by 5-7 cm.
• Increased minute ventilation.
• Tidal volume increases by 30-40%.

Acid-Base Equilibrium

• Pregnancy leads to a compensated respiratory alkalosis.
• Increased carbon dioxide (CO2) excretion per minute.
• Slight increase in pH (7.44+).
• Increased partial pressure of oxygen (PaO2), decreased partial pressure of carbon dioxide (PaCO2) (40-30).
• A larger gradient for both O2 and CO2 at the placenta, facilitating gas exchange.

Gastrointestinal Changes

• Slowed GI motility (progesterone effect): constipation and early satiety.
• Relaxation of lower esophageal sphincter (LES): gastroesophageal reflux disease (GERD).
• Nausea and vomiting: often linked to human chorionic gonadotropin (HCG) levels.
• Liver and gall bladder: biliary stasis, cholesterol saturation, increased stone risk.
• Increased liver production of clotting factors, leading to a greater tendency for clotting.
• Increased binding proteins for thyroid hormones, steroids, and vitamin D, altering free hormone levels.

HCG and Thyroid

• HCG can mimic thyroid-stimulating hormone (TSH) at the thyroid gland.
• Increased T3/T4 levels may contribute to first-trimester nausea.
• If TSH levels are mildly abnormal in the first trimester, check T3/T4 and recheck in the second trimester.

Orthopedic Adaptations

• Shift in center of gravity.
• Altered gait.
• Increased joint laxity.
• Widening of the symphysis pubis.

Erectile Dysfunction

• Most common sexual problem in men
• Consistent inability to achieve or maintain an erection sufficient for sexual intercourse
• Negatively impacts quality of life
• Often caused by arterial insufficiency
• May be an early sign of cardiovascular disease
• Antihypertensive, antidepressants, and opioid medications are associated with erectile dysfunction (e.g., beta-blockers, diuretics, SSRIs/SNRIs, hydrocodone)

Epidemiology of Erectile Dysfunction

• More than half of men aged 40-70 years have erectile dysfunction
• Incidence increases with age
• Most have an organic rather than a psychological cause

Risk Factors for Erectile Dysfunction

• Age
• Prostate disorders (e.g., cancer, benign prostatic hyperplasia)
• Hypogonadism (insufficient testosterone production)
• Vascular disease
• Chronic obstructive sleep apnea
• Hypertension
• Diabetes
• Alcohol use
• Tobacco use
• Recreational drug use
• Medication adverse effects (e.g., SSRIs/SNRIs, beta-blockers, opioids)
• Peyronie's disease
• Psychological disorders (e.g., depression, anxiety)

Labs and Work-up for Erectile Dysfunction

• Urinalysis
• Fasting serum lipid profile
• Serum glucose, HbA1c
• Serum total testosterone (free circulating/unbound to protein, and bound to protein)
• TSH
• Serum prolactin
• Patients with abnormal testosterone levels should have measurement of free testosterone and luteinizing hormone (LH) to differentiate hypothalamic-pituitary dysfunction from primary testicular failure

Imaging and Diagnostic Studies for Erectile Dysfunction

• Duplex Doppler ultrasound and penile cavernosography can distinguish arterial from venous erectile dysfunction, helping predict which patients may benefit from vascular surgery.
• Direct injection of vasoactive substances into the penis (e.g., prostaglandin E1 or papaverine)

Considerations for Erectile Dysfunction

• Thorough review of past medical history and any new chronic conditions that may play a role (e.g., diabetes, hypertension, cardiovascular disease, peripheral vascular disease, endocrine disorders, neurological disorders, kidney disease, cancer, trauma, surgery)
• Patient body mass index; obesity
• Social history (alcohol, tobacco, recreational drug use, THC use)
• History and physical examination are sufficient to make the diagnosis of erectile dysfunction

Treatment and Management of Erectile Dysfunction

• First-line therapy consists of oral phosphodiesterase type 5 inhibitors (e.g., sildenafil, vardenafil, tadalafil).
• Contraindicated in patients taking nitroglycerine or nitrates due to hypotension and syncope concerns.
• Intracavernous injection of prostaglandin E1 (alprostadil) or papaverine (vasodilator)
• Alprostadil urethral suppository pellets
• Surgery (penile prosthesis implanted into the paired corpora cavernosa)
• Therapeutic procedures like vacuum erection devices (draw blood into corpora cavernosa)

When to Refer for Erectile Dysfunction

• Patients with unsatisfactory response to oral medications
• Patients with Peyronie's disease or other penile deformity (urology)
• Patients with a history of pelvic or perineal trauma, surgery, or radiation (urology)
• Patients with priapism to the emergency department for immediate intervention to allow restoration of penile perfusion (emergency department)

Priapism

• Full or partial erection lasting more than 4 hours
• Prolonged painful penile erection in the absence of sexual stimulation
• Leads to ischemic injury of the corpora cavernosa, increasing the risk of impotence
• Ischemic priapism is a medical emergency requiring immediate medical or surgical intervention to avoid irreversible penile damage
• Early recognition (within hours) and prompt treatment of priapism offer the best opportunities to avoid impotence

Etiology of Priapism

• Idiopathic in 60% of cases
• The remaining 40% of cases are associated with:
  • Certain diseases (e.g., leukemia, sickle cell disease, pelvic tumors, pelvic infections)
  • Penile trauma
  • Spinal cord trauma
  • Medications
  • Alcohol
  • Cocaine
  • Currently, intracavernous injection therapy for impotence may be the most common cause

Peyronie's Disease

• Common disorder caused by scar formation within the erectile bodies of the penis, resulting in pain, penile deformity, and sexual dysfunction
• Examination of the penile shaft will disclose a thickened plaque, typically on the dorsum.
• Imaging modalities:
  • Ultrasound is useful for detecting Peyronie's disease.
  • Direct injection of vasoactive substances into the penis (e.g., prostaglandin E1 or papaverine) can reveal penile curvature.

Peyronie's Disease Clinical Presentation

• Scar tissue
• Significant bend to the penis
• Trouble maintaining erections
• Possible penile shortening
• Variable amount of pain

Peyronie's Disease Treatment and Management

• Watchful waiting
• Traction therapy
• Injection therapy
• Collagenase injections (the only FDA-approved medication for the treatment of Peyronie's disease)
  • Injected into the central portion of the plaque by needle.
  • Causes enzymatic digestion of the lesion, leading to subsequent correction of penile curvature over time.
• No oral therapies are FDA-approved.
• Surgery is an alternative for men with severe curvature or lesions causing penile instability (last resort).
• Outpatient urology referral is warranted

Penile Cancer

• Exhibits a predictable pattern of local, regional, and systemic spread
• The earliest route of metastasis is to the regional inguinal and iliac nodes
• Metastasis is characterized by a relentlessly progressive course, leading to death for most untreated patients within two years.
• Metastatic enlargement of the regional nodes can result in skin necrosis, chronic infection, sepsis, and hemorrhage secondary to femoral vessel erosion
• Tumor, node, metastasis (TNM) staging system is used for penile cancer staging

Penile Cancer Risk Factors:

• Lack of circumcision
• HPV infection
• Phimosis
• Smoking

Epidemiology of Penile Cancer

• Most commonly affects men between 50 and 70 years of age.
• Accounts for less than 1% of all malignant neoplasms among men in the United States.
• Squamous cell carcinoma (SCC) is the most common histologic subtype, accounting for more than 95% of cases.

Penile Cancer Imaging and Work-up

• Patients with clinically palpable lymph nodes should undergo imaging to define the full extent of the disease.
• CT and MRI imaging depend primarily on lymph node enlargement for detection of metastases.
• CT has often been the imaging modality chosen in penile cancer to examine the inguinal and pelvic areas, as well as to rule out distant metastases.
• In known inguinal metastases, CT-guided biopsy of enlarged pelvic nodes can help with consideration of neoadjuvant chemotherapy.

Penile Cancer Treatment and Management

• Surgical amputation of the primary tumor remains the gold standard for definitive treatment

Phimosis

• Condition where the contracted foreskin cannot be retracted over the glans penis
• May appear as a tight ring or "rubber band" of foreskin around the head of the penis.
• Chronic infection from poor hygiene is the most common cause
• Most cases occur in uncircumcised males.
• Squamous cell carcinoma (SCC) may develop under the foreskin, increasing the risk of penile cancer.
• In diabetic older men, chronic balanoposthitis may lead to phimosis.
• Balanoposthitis is an inflammatory condition of the foreskin and glans that affects uncircumcised men (e.g., infections like Candida).

Phimosis Clinical Presentation

• Edema
• Erythema
• Tenderness of the prepuce
• Presence of purulent discharge

Phimosis Management

• Circumcision is curative.
• Topical steroid treatment (e.g., betamethasone 0.05% to 0.10% twice daily) applied from the tip of the foreskin to the glans penis for 1 to 2 months, along with daily manual preputial retraction, is an effective nonsurgical management option for phimosis.
• Initial infection should be treated with broad-spectrum antimicrobials.

Paraphimosis

• Condition where the foreskin, once retracted over the glans penis, cannot be replaced in its normal position due to chronic inflammation.
• Results in phimosis and formation of a tight ring of skin when the foreskin is retracted behind the glans.
• This skin ring causes venous congestion leading to edema and enlargement of the glans penis.
• As the condition progresses, arterial occlusion and necrosis of the glans may occur.
• Usually, can be treated by firmly squeezing the glans for 5 minutes to reduce tissue edema and decrease the size of the glans.
• The skin can then be drawn forward over the glans.
• Occasionally, the constricting ring requires incision under local anesthesia.
• Antibiotics should be administered, and circumcision should be done after inflammation has subsided.

Balanitis

• Inflammation and pain of the glans (head) of the penis.
• Most often occurs in uncircumcised males and boys younger than 4 years old.
• Typically caused by yeast infection, but can be due to bacterial and viral infection etiology.
• Estimated that up to 10% of males will have balanitis during their lifetime.

Types of Balanitis

• Balanitis (Zoon's balanitis):
  • The main type of balanitis
  • Usually affects uncircumcised, middle-aged men
  • Causes an inflamed, red penis head.
• Circinate balanitis:
  • Result of reactive arthritis.
  • In addition to inflammation and redness, causes small lesions (sores) on the head of the penis.
• Pseudoepitheliomatous keratotic and micaceous balanitis:
  • A rare form of balanitis, resulting in scaly warts on the glans.

Balanitis Clinical Presentation

• Pain and irritation on the glans penis.
• Erythema/redness on the glans penis.
• Itching under the foreskin.
• Swelling/inflammation.
• Areas of shiny or white skin on the penis.
• White discharge (smegma) under the foreskin.
• Foul smell.
• Painful urination.
• Sores or lesions on the glans (rare and appears with a type of balanitis that affects men older than 60).

Balanitis Diagnosis

• Often made clinically through physical examination.
• May need to swab the urethral opening for testing.
• Urinalysis
• CBC with differential
• Labs to check for diabetes
• STD check

Balanitis Treatment and Management

• Antifungal creams (e.g., clotrimazole) for yeast infections.
• Antibiotics to treat any infections, including STDs.
• Improved hygiene: Wash and dry under the foreskin regularly.
• Diabetes management: Lifestyle modifications with good blood sugar control.
• Circumcision: Usually considered if symptoms recur.

Ppt 8: Physiologic Changes in Pregnancy, Ppt 9: Penile Disorders ppt