PATH375 Urinary Tract and Male Reproductive System

Upper urinary tract

Kidneys and ureters

Lower urinary tract

Bladder, urethra, and prostate (in men)

Transitional epithelium (urothelium)

Type of epithelium that lines the collecting system, ureters, bladder, and urethra

Nephron

Basic functional unit of the kidney, composed of glomerulus, tubules, and collecting duct

Normal daily urine production

1.5 liters per day (24 hours)

Glomerular filtration barrier

Consists of three structures: endothelial cell, basement membrane, and epithelial cell

Renin

Hormone secreted by kidney that raises blood pressure

Erythropoietin

Growth factor secreted by kidney that stimulates production of RBCs in bone marrow

Oliguria

Decreased urine production

Anuria

No urine production

Polyuria

Increased urine production

Hematuria

Passage of blood in urine

Proteinuria

Protein in urine

Azotemia

Elevated blood urea nitrogen (BUN) and creatinine

Urinary casts

Particles seen during urinalysis; the type (RBC vs WBC cast) helps determine cause of renal pathology

PHARAOH mnemonic

Nephritic syndrome findings: Proteinuria, Hematuria, Azotemia, RBC casts, Anti-strep titers, Oliguria, Hypertension

Acute cause of nephritic syndrome

Post-streptococcal glomerulonephritis

Chronic cause of nephritic syndrome

Systemic lupus erythematosus (SLE)

Nephrotic syndrome proteinuria threshold

3.5 g/day with resulting hypoalbuminemia and edema

Key features of nephrotic syndrome

+++Proteinuria (>3.5g/day), hypoalbuminemia, edema, hyperlipidemia, lipiduria

Why nephrotic patients get infections/thrombi

Due to loss of proteins involved in immunity and coagulation

Most common cause of nephrotic syndrome in children

Minimal change disease (lipoid nephrosis, nil disease)

Most common cause of nephrotic syndrome in adults

Focal segmental glomerulosclerosis (FSGS)

Membranous nephropathy

Common cause of nephrotic syndrome in adults; characterized by diffuse thickening of glomerular basement membrane due to immune complex deposition; 85% are primary/idiopathic

Minimal change disease characteristics

Most common nephrotic syndrome in children; unknown etiology; responsive to corticosteroids

FSGS abbreviation

Focal (some) Segmental (sections) Glomerulo (of kidney filters) Sclerosis (are scarred)

Secondary causes of FSGS

HIV, heroin, sickle cell disease, obesity

Diabetic nephropathy pathologic findings

Glomerulosclerosis, arteriosclerosis, papillary necrosis, pyelonephritis

Acute renal failure (acute kidney injury)

Acute onset of decreased urine production developing over days to weeks; usually reversible

Three categories of acute renal failure causes

Prerenal (decreased renal perfusion), Renal (glomerular disease), Postrenal (ureteric obstruction)

Chronic renal failure (chronic kidney disease)

Insidious decrease in renal function (eGFR) due to damaged kidneys

Normal eGFR

≥90 ml/min/1.73 m²

End-stage renal disease (ESRD)

Stage 5 chronic kidney disease with eGFR <15; requires dialysis or transplant

Autosomal dominant polycystic kidney disease (ADPKD)

Most common inherited kidney disease; progressive large cysts with age; most develop renal failure by 40-50 years; both kidneys greatly enlarged

Autosomal recessive polycystic kidney disease (ARPKD)

Childhood PKD; presents early in life with large numbers of small cysts

Cystic renal dysplasia

Sporadic congenital disorder; usually unilateral affecting children; abnormal differentiation with persistence of cartilage and immature elements

Horseshoe kidney

Fusion of kidneys in midline; occurs in ~1/800 births; asymptomatic but increased risk of UTIs, stones, and renal tumors

Cystitis

Inflammation of the bladder

Pyelonephritis

Inflammation of the kidney

Two mechanisms of kidney infection

Hematogenous spread (sepsis, septic emboli) and ascending infection (more common)

Common bacteria causing cystitis

Gram negative bacteria: E. coli, Proteus

Why cystitis is more common in females

Shorter urethra

Cystitis symptoms

Dysuria (painful urination), increased frequency with small amounts of urine, cloudy urine

Acute pyelonephritis

Inflammation of kidney usually due to bacterial infection; most commonly E. coli ascending through urinary tract

Predisposing factors for pyelonephritis

Bladder obstruction, urinary stones, vesicoureteral reflux, pregnancy

Signs and symptoms of pyelonephritis

Flank pain, fever, costovertebral angle tenderness

Calcium stones

Most common type of renal stone; visible on x-ray; associated with hypercalcemia

Struvite stones

Associated with UTIs; relatively larger; may form large staghorn calculi occupying renal pelvis

Uric acid stones

Associated with hyperuricemia

Cystine stones

Seen in patients with inborn errors of amino acid metabolism

Renal colic

Severe, sudden onset flank pain radiating to abdomen/groin; colicky pain from dilation, stretching, and spasm of ureter caused by obstruction from stone

Renal cell carcinoma

Most common renal tumor; malignant neoplasm of renal epithelial cells; most are sporadic

Renal cell carcinoma presentation

Asymptomatic mass discovered incidentally, flank pain, hematuria, or paraneoplastic syndromes (hypercalcemia)

Von Hippel-Lindau disease association

Familial renal cell carcinoma due to mutation of tumor suppressor gene

Wilms tumor (nephroblastoma)

Most common solid tumor of children; mutation of WT-1 or WT-2 tumor suppressor genes; presents between 2-4 years of age

Transitional (urothelial) cell carcinoma

Most common urinary tract malignancy; malignant neoplasm of transitional epithelium in bladder

Bladder cancer presentation

Hematuria, dysuria, pain

Most important risk factor for bladder cancer

Smoking

Other risk factors for bladder cancer

Aniline dyes, Schistosomiasis

Gross appearance of bladder tumors

Papillary (usually low grade, good prognosis) vs flat (usually high grade, worse prognosis)

Components of male reproductive system

2 testes in scrotum, epididymis, vas deferens, seminal vesicles, prostate, penis

Where sperm production occurs

Within seminiferous tubules in the testes

Sertoli cells

Supporting sex-cord stromal cells in seminiferous tubules

Leydig cells

Cells in testes that produce testosterone; secretion controlled by pituitary gonadotropins

Cryptorchidism

Failure of testicles to descend into scrotum; associated with 10X risk of malignant transformation and infertility

Hypospadias

Abnormal opening of urethra on lower side of shaft of penis

Epididymitis causes in young men

Sexually acquired infections: Gonorrhea, Chlamydia

Epididymitis causes in older men

Stagnation of urine leading to uropathogens/gram negative bacteria like E. coli

Orchitis

Isolated inflammation of testis or combined with epididymitis; may be complication of hematogenous spread or viruses (mumps)

Balanitis

Inflammation of glans penis; usually caused by virus (HSV) or bacteria (syphilis)

Genital herpes

HSV-2; vesicular eruptions with clear serous fluid that rupture forming shallow painful ulcers; no cure, remains dormant in neural ganglion cells

Gonorrhea

Neisseria gonorrhoeae causing purulent urethritis; dysuria and yellow urethral discharge; complications include ascending infection and hematogenous spread causing arthritis

Chlamydia

Most common cause of bacterial urethritis in men; caused by Chlamydia trachomatis; many men asymptomatic

Reiter's syndrome (reactive arthritis)

"Cannot pee, see, or bend knee" - urethritis, conjunctivitis/uveitis, arthritis associated with Chlamydia

Syphilis primary stage

Painless ulcer on glans penis (primary chancre) caused by Treponema pallidum

Syphilis secondary stage

Fever, malaise, rash, hepatitis, kidney disease due to systemic spread

Syphilis tertiary stage

Gummas (syphilitic granulomas), vasculitis, cardiac and CNS complications

Testicular tumor incidence

Most common malignant neoplasms of young adult males (~20-40 years); relatively uncommon overall; most are germ cell origin and malignant

Tumor markers in testicular cancer

Different testicular neoplasms produce different substances (HCG, AFP) that can be measured in blood to identify presence of tumor

Seminoma

Most common germ cell tumor; peak incidence at 40 years; no serologic tumor markers; sensitive to radiation therapy; good prognosis

Non-seminomatous germ cell tumors

Peak incidence at 30 years; may produce HCG or AFP; poorer prognosis than seminoma due to metastatic disease at presentation

Types of non-seminomatous germ cell tumors

Embryonal carcinoma, yolk sac tumor, teratoma, choriocarcinoma

Benign prostatic hyperplasia (BPH)

Benign hyperplasia and hypertrophy of prostate epithelium and stroma; common in elderly males; unclear hormonal pathogenesis

BPH symptoms

Urgency, frequency, dribbling, nocturia (waking at night to urinate); increased bladder infections

Prostatic carcinoma

Most common cancer in males; third most common cause of cancer-related deaths in males; usually adenocarcinoma in elderly males

Where prostatic carcinoma arises

Most arise in peripheral zone (vs BPH in transition zone); does not cause urethral compression so usually no urinary symptoms

Prostate-specific antigen (PSA)

Produced by prostate cells and secreted into semen; small amount in blood normally; prostate cancer cells produce more PSA leading to elevated blood levels; useful for screening but also elevated in BPH and prostatitis

Gleason score

Sum of primary (most predominant) and secondary (second most predominant) Gleason grade; ranges from 2-10; important parameter for prognosis