Male genital & urinary pathology

Congenital abnormalities

• defects are quite common, about 1% of all male births

• Cryptorchidism

• hypospadias

• espispadias

Hypospadias and Epispadias

• Urethra opens into ventral surface (underside) of penis

• more common: 3 in 1,000 live born males

• Urethra opens onto dorsal (upper sect) surface of penis

• uncommon: 1 in 100,000 live born males

• more severe associations than hypospadias

• both result in partial urinary obstruction that predisposes to infection

• have defective ejaculation that may reduce fertility

Cryptorchidism

• absence of one or both testicles from the scrotum

• most common development defect in male GU tract

  • affects over 3% of full-term newborns

• in most cases testes will descend by 3 months, but 1% are still undescended at 1 yr

• sperm production requires a lower temp

• testes descend from the abdomen into the scrotum in utero or shortly after birth

  • testes not descended into scrotal sac greatly increases infertility

• increases risk of testicular cancer later in life

Characteristics of STDs

• caused by many different organisms

• individuals may suffer from more than 1 STD at a time

• initial symptoms almost always occur at site of infection

• disease symptoms almost always clinically more apparent in males

• infections usually cause systemic disease

• infection transmitted from mother to child in utero or during birth

Herpes

• caused by HSV

• HSV-1 usually caused “cold sores” in mouth/lips

• both types produce life-long infection, but virus usually remains dormant

• drugs can reduce outbreaks

• active genital herpes produces painful blisters at infection site

Bacterial STD infections

• syphilis: a corkscrew-shaped bacteria (spirochete)

• chlamydia: obligate intracellular bacerium, very common STF

• Gonorrhea: bacterium, very common STD

• Trichomonas: parasite

• bacterial infections cause Urethritis: inflammation of urethra, often with a discharge of a purulent exudate (pus)

• co-infection with more than 1 STD is common!

Syphilis

• caused by Treponema pallidum. Infection has 3 distinct stages if not treated

• Primary syphilis: characterized by a chancre, a solitary painless ulceration at site of infection, appear ab 1-3 weeks after exposure, may persist for 3-6 weeks w/o treatment

• secondary syphilis: characterized by a systemic spread of spirochetes and a skin lesion known as Condyloma lata, multiple slightly raised lesions, appear 2 months to 2 yrs after infection

• tertiary syphilis: rare, characterized by a lesion known as Gumma, soft and rubbery non-cancerous growth filled granulomas, appears 2-20 yrs after infection, can be very disfiguring. Can also involve ❤ and CNS

Balanitis

• inflammation of the head and foreskin of the penis

• largely idiopathic but known association with genital herpes

• affects 11% of adult men and 3% of children

• much more common in uncircumcised males

Orchitis

• inflammation of the testes

• usually associated viral infections (mumps)

Prostatitis

• inflammation of the prostate gland

• usually an acute illness with fever, back pain, dysuria and other urination problems

• usually infection with GN uropathogens, E. coli is a frequent cause

• location of the prostate males inflammation/infection of this gland a painful lesion

Hydrocele

• Accumulation of fluid around a testicle, this is relatively common

• caused by fluid secreted from the tunica vaginalis

• a simple method of diagnosing a hydrocele vs a tumor is to shine a strong light through the enlarges scrotum

  • hydrocele will usually allow light to pass

Hematocele

• collection of blood in the tunica vaginalis caused by trauma to testes

• more painful than a hydrocele

Varicocele

• abnormal enlargement of the venous plexus of the scrotum (pampiniform plexus) which drains the testicles

• cause:

  • defective valves

  • compression of vein

• usually harmless but may affect infertility

Testicular torsion

• a urologic surgical emergency

• very painful condition

• delay in diagnosis and treatment can lead to infarction and loss of the testicle

• requires surgery, time is key factor for preservation of testicle:

  • <6 hrs -90%

  • 12 hrs - 50%

  • 24 hrs - 10%

  • >24 hrs - 0%

Benign Prostatic Hyperplasia (BPH)

• increase in size of prostate due to glandular hyperplasia

• highest in males of African lowest in males of East Asian

• BPH does NOT predispose to prostate cancer

• causes multiple symptoms relating to urination, increased size may obstruct urethra and increase infection risk

Male genital tract tumors

• penis: squamous cell carcinoma of skin (HPV may be a cause)

• prostate: adenocarcinoma

• testis: cancer of young men, incidence peaks ages 24-45

• testicular cancers respond well to chemotherapy and have a 5-yr survival rate >90%

• Rule of 90’s for testicular cancer: 90% age 25-45, 90% germ cell tumors, 90% malignant, 90% curable

Testicular seminoma

Prostatic adenocarcinoma

• most common male cancer (non-skin) in the US

• 2nd leading cause of cancer-related deaths in males

• incidence increases with age (cancer of old men), but incidence and mortality rates in US are declining

• no specific symptoms, usually clinically silent, urinary symptoms sometimes can mimic nodular hyperplasia (BPH)

• some men may present with severe back pain due to metastasis to vertebral bone (most often with aggressive form)

• treatment for localized (non-metastatic) cancer is effective

Neuroendocrine carcinoma

• aggressive prostate cancer variant that is R to treatment

• metastasizes early in disease and has poor survival

• ab 1% of total prostate cancer cases

Prostate specific antigen (PSA)

• protein produced by cells of the prostate gland

• blood test measures circulating levels of PSA

• FDA has approved of PSA blood test along with digital rectal exam (DRE) to screen for prostate cancer in men 50 and older

• PSA test is also approved to monitor patients with a history of prostate cancer for recurrence

Prostate cancer diagnosis

Cystitis

• inflammation of the urinary bladder

• many causes including UTI, trauma (catheter), kidney stones, collateral dmg radiation or chemo

• most caused by ascending infection with fecal bacteria (E. coli)

• more common in females, children, elderly, individuals confined to bed

• acute cystitis caused by UTI is very effectively treated with short course of antibiotics

Carcinoma of the urinary bladder

• 4 types depending on cell from which the cancer developed

• primary cause is cigarette smoking and/or occupational exposure to chemicals

• peak incidence ages 55-80, more common in males (M:F = 3:1)

• less invasive and less prone to metastasize than other cancers

• surgical resection is preferred treatment

• most tumors (70-75%) are low grade with good prognosis

Urinary tract obstructions

• any obstruction will predispose to an infection (usually bacterial)

• urinary tract can be obstructed by many processes

• in each case infection is a potential complication

Congenital: Ectopic kidney

• kidney is located in an abnormal position

• there are several different variants depending on location

• usually doesn’t cause issues

• less often, the ectopic kidney may cause problems such as urine blockage, infection, or urinary stones

Congenital: horseshoe kidney

• both kidneys are fused tgt at the midline as a single organ

• associated with chromosomal defects: Turner syndrome (one X chromosome) Edwards syndrome (Trisomy 18)

• can also occur as an isolated anomaly in about 0.1 to 0.2% of the general population

• usually asymptomatic

Congenital: Dysplastic kidney

• AKA Multicystic dysplastic kidney (MCDK)

• malformation during fetal development resulting in disorganized architecture of the cortex and medulla

• usually only 1 kidney, often with minimal clinical impact

• degree of abnormality (cysts) will determine kidney function

• multiple cysts often cause urinary tract obstruction

Hereditary: Autosomal dominant polycystic kidney disease (ADPKD)

• common inherited disorder: affects 1 in 500 persons

• disease usually presents in the early-mid 40’s with hypertension and urinary problems (infections, hematuria)

• cysts lead to renal failure, 10-15% of ADPKD are on dialysis

• ab 1/3 of ADPKD have berry aneurysms in the brain, Brain hemorrhages account for up to 10% of deaths in ADPKD patients

Pyelonephritis: Kidney infection

• inflammation triggered by a bacterial infection

• infection can involve renal parenchyma, calyces or pelvis

• over 80% of infections arise from an ascending UTI with fecal bacteria (E. coli and others). UTI involving kidney is a complicated UTI and is more difficult to treat

• 10% are caused by a blood infection due to bacteremia, often with Staphylococcus (IV drug use)

Acute pyelonephritis

• critical that antibiotic treatment is prompt and complete

• acute pyelonephritis can progress rapidly to sepsis and death

• chronic pyelonephritis: may develop in persons with a structural defect of the kidney, very difficult to treat, results in destruction of the kidney

Renal cell carcinoma

• tumors may arise anywhere in the kidney, but more often it affects the hilum

• tumors are spherical solid masses, which can vary in size (often large)

• characteristic color: bright yellow-gray-white

• necrosis and hemorrhage are common

• can invade extend into renal vein and inferior vena cava

Wilms tumor (Nephroblastoma)

• most common kidney tumor of childhood (ages 2-5)

• 90% are sporadic, less than 10% associated with WT1 or WT2 mutations

• Presents as large abdominal mass

• responsive to surgery and chemotherapy, 90+% cure rate

• increases risk of developing other cancers (leukemia)

Kidney disease related to blood (ends with emia)

• Azotemia: accumulation of nitrogenous wastes in the blood: creatinine and blood urea nitrogen (BUN)

• Uremia: azotemia with clinical signs of kidney disease

• Hyperkalemia: elevated blood potassium lvls (can cause sudden cardiac arrest)

Kidney disease relate to urine (ends with uria)

• Anuria: no production of urine (<50ml in 24 hrs)

• Dysuria: pain during urination

• Hematuria: blood in the urine

• Oliguria: decreased urine production (<400ml in 24hrs)

• Polyuria: excessively increased production of urine (as in diabetes)

• Proteinuria: protein (largely albumin) in the urine

• Pyuria: pus in urine

Major kidney functions

• removal of waste products and foreign substances

• regulation of plasma ion composition: sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphates

• regulation of plasma volume

• regulation of blood pH (acid-base balance)

• secretion of renin: regulates BP

• secretion of Erythropoietin: stimulates erythrocyte production

• activation of vitamin D: converts the stable 25-hydroxyvitamin D to the active steroid hormone 125-dihydroxyvitamin D

The nephron

• functional unit, ab 1 million per kidney

• Nephron = Glomerulus (filtering unit) + Tubule (collects filtrate)

• kidney can only function normally with only 25% of total filtering capacity (functional nephrons)

Glomerular blood supply

• glomerular capillary bed is the only one to have arterioles on both sides

• blood enters glomerulus via the afferent arteriole →

• branches into extensive capillary network →

• capillaries converge to form the efferent arteriole (E for exit, A before E)

Glomerulus: development

• during embryological development, arterioles “push” into the tubules

• additional cell types are created and mature into functional glomerulus

Endothelial cells (EC)

• specialized type known as fenestrated endothelial cells

• they line the capillary loops, have large pores in their cytoplasm that function as the 1st part of the glomerular filtration barrier

Glomerular basement membrane (GBM)

• specialized basement membrane (thicker with diff connective tissue proteins) that separates endothelial cells from the podocytes (both cell types make the GBM)

• This GBM functions as the 2nd part of the glomerular filtration barrier

Podocytes (glomerular epithelial cells)

• large specialized epithelial cells with long cytoplasmic extensions that form “foot processes” that wrap the GMB and ECs

• foot processes of adjacent podocytes interdigitate to form slit pores

  • function as the 3rd part of the glomerular filtration barrier

Bowman’s space

• after blood is filtered through the glomerular filtration barrier the filtrate is captured in this space before entering the proximal convoluted tubule

• bowman’s space is continuous with the proximal tubule

Mesangial cells & mesangial matrix

• function as “maintenance” cells of the glomerulus

• both cells and matrix tgt function as an “anchor” to hold the capillary loops tgt and maintain integrity of the glomerulus

Glomerular filtratoin barrier

1. Glomerular endothelial cell: negatively-charged glycocalyx (polysaccharide molecules on cell surface) and pores in the endothelial cytoplasm (fenestrations)

2. glomerular basement membrane (GBM)

3. slit pores formed by adjacent podocytes

Glomerulus: blood pressure regulation

• afferent arterioles adjacent to distal tubule can dilate or constrict based on the composition of the filtrate

  • this regulates BP

• if BP is too low, juxtaglomerular cells secrete renin

  • results in arteriole constriction to increase BP and tubules retains/reabsorbs salt from filtrate

Nephron tubules

1. Proximal tubule: reabsorption of many molecules (including proteins) in the filtrate back into blood. Proximal tubule epithelial cells also activate vitamin D

2. Loop of Henle: water and salt reabsorption

3. Distal tubule: concentrates filtrate, BP regulation

4. collecting ducts: at this point filtrate is now urine

5. Calyx

6. Pelvis

7. Ureter

8. Urinary bladder

Glomerulonephritis

• Inflammation of glomeruli

• not a single disease but broad term used to refer to many types of inflammatory conditions that most often affect both kidneys

• children: 95% is primary kidney disease

• adults: 60% primary disease 40% secondary to diabetes

Causes of glomerulopnephritis

• immune-mediated

• metabolic

• circulatory

• methods of classification:

  • clinical syndrome: nephritic vs nephrotic

  • glomerular pattern: proliferative vs. non-proliferative

Causes of glomerular pathology

• Immune-mediated: most significant mediator of glomerular damage

  • abnormal immune response to infections and autoimmune diseases are major causes

  • involves both immune complexes and anti-GBM antibodies that activate complement, which then will recruit and activate neutrophils that damage the glomeruli

• Metabolic: diabetes induces a specific type of glomerular disease. Kidney failure is the major cause of death in diabetics

• Circulatory: anything that reduces BF to the kidney that can lead to renal failure

  • disseminated intravascular coagulation (DIC) often triggered by bacterial sepsis is a major cause

Clinical presentation of glomerular injury (nephritic)

• Azotemia: nitrogenous wastes in blood

• Hematuria: blood in urine

• Hypertension: high BP

• Oliguria: decreased urine production

Clinical presentation of glomerular injury (nephrotic)

• edema: generalized edema due to water retention

• Proteinuria: protein (mostly albumin) in the urine

• hyperlipidemia: increased lipids in blood (this is variable and not always observed in the nephrotic syndrome)

Nephritic syndrome

• Glomeruli are “clogged” due to inflammation and glomerular hypercellularity: resulting in decreased filtration

• decreased filtration causes oliguria and azotemia

• kidney will increase BP (hypertension) for filtration

• increased BP forces RBCs through damaged glomerular filtration barrier (hematuria)

• nephritic syndrome diseases have increased cells in the glomerulus (hypercellularity) and are classified as Proliferative

nephrotic syndrome

• glomerular filtration barrier is damaged “leaky” so that protein is lost in the urine (proteinuria) faster than can be replenished

• loss of protein in the blood (hypoalbuminemia) decreases the oncotic pressure in the microvasculature, allowing fluid to accumulate in tissues (edema): generalized edema

• there is a compensatory increase in proteins and lipoproteins by the liver, but lipoproteins (main lipid carriers) are not lost in the urine so there often is hyperlipidemia

• usually do not have increased # of cells in glomerulus, classified as non-proliferative

Diagnosis of glomerular disease

• must use special lab techniques for precise diagnosis of the type of glomerulonephritis, which will determine treatment

Nephritic: IgA nephropathy

• most common form of glomerulonephritis world-wide, mainly affects young adults (16-35)

• characterized by glomerular deposition of IgA antibodies and complement

• most causes are idiopathic, but may occur after flu-like illness, also occur in association with a type of small-vessel vasculitis

Nephritic: acute glomerulonephritis

• disease prototype is post-infectious glomerulonephritis usually after group A B-hemolytic streptococci infection

• usually in children, in ab 1-3% cases this occurs ab 1-2 weeks after strep throat infection

• prompt antibiotic treatment can prevent possible kidney damage

• 95% recover, 5% progressive to chronic renal disease

• glomerular inflammation caused by an autoimmune reaction of to glomerular (self) antigens (anti-glomerular IgG antibodies)

• immune complexes induce Type III hypersensitivity reaction and activate complement, that recruit neutrophils

• glomerular histology shows diffuse proliferation of glomerular cells and presence of neutrophils

Nephritic: rapidly progressive (Crescentic) Glomerulonephritis (RPGN)

• rapid and progressive destruction of glomeruli, can result in renal failure within weeks to months

• the classic histologic picture is presence of crescents (hypercellularity with fibrin) in the glomeruli which obliterate Bowman’s space

• many causes, often autoimmune diseases, example is Goodpasture’s syndrome: anti-GBM (also affects lungs)

• grossly, kidneys are swollen, pale with “flea-bitten” petechial hemorrhages on the kidney surface

• only treatment is dialysis and kidney transplant

Nephritic: membranoproliferative glomerulonephritis (MPGN)

• MPGN accounts for 10-20% of glomerulonephritis cases in children and young adults

• presents as mixed nephritic/nephrotic syndrome

• many causes, post-infectious reaction and/or autoimmune diseases

• the classic histologic pictureL thickening of GBM, proliferation of glomerular cells and presence of neutrophils

• complement activation plays a major role in MPGN pathogenesis

• slowly progressive unremitting course that eventually requires transplant (50% of cases 10 yrs after diagnosis)

Nephrotic: minimal change glomerulonephritis

• Also known as Nil Disease since no abnormalities found by light microscopy, requires electron microscopy to see pathology

• Occurs mainly in children (2-6 years old) and is most common

  kidney disease of childhood, generalized edema (anasarca) is the most prominent clinical sign

• Relatively benign disease that doesn’t progress to renal failure

• Unknown cause, there are NO immune complexes or complement activation

• By light microscopy glomeruli appear normal, but electron

  microscopy shows fusion of the podocyte foot processes

• Corticosteroid therapy is effective, long-term prognosis is good

Nephrotic: membranous gelomerulonephritis

• Most common cause of primary kidney disease in adults, most often persons in their 50’s and 60’s

• Usually idiopathic, but can occur as a secondary reaction to autoimmune diseases (SLE), cancers, reaction to drugs

• Glomerular pathology is characterized by thickening of the glomerular basement membranes and leakiness of the glomerular capillaries

• Corticosteroid therapy is somewhat effective, but 50% have a slow progression to renal failure

Nephrotic: Focal segmental Glomerulosclerosis (FSGS)

• Most common cause of adult proteinuria in the U.S.

• Usually idiopathic, but can occur in association with autoimmune diseases (SLE), IV drug abuse, HIV infection

• Increased collagen deposition affects only a portion of each glomerulus (segmental) and is focal

• Less than 50% of glomeruli are affected

• HIV nephropathy: a more severe variant of FSGS associated with HIV infection

• Most persons progress to renal failure 5 to 10 years after diagnosis

Acute interstitial nephritis:

• somewhat common, many cases could be sub-clinical

• toxins (plant and fungal-derived) and certain drugs (antibiotics and NSAIDS) are known to trigger

• possibly an allergic type reaction since serum IgE is increased and the kidney lesions have a large # of eosinophils

• usually self-limiting, but severe cases may need dialysis while the tubules regenerate

Chronic interstitial nephritis

• similar to acute but with a slow insidious onset

• increased collagen deposition in the interstitial tissue surrounding tubules results in fibrosis causing renal failure

Hypertension

• kidney can cause

• kidney is a major target of dmg due to hypertension

• perhaps most common cause of renal disease

• 2 major types:

  • essential hypertension (benign)

  • hypertensive crisis (malignant)

Essential hypertension

• The typical common form of hypertension, >95% cases

• Chronic and modest elevations in blood pressure

  • Stage 1 hypertension: 130-139/80-89 Stage 2: >140/90

• Chronic hypertension causes kidney arterioles to thicken to cope with the increased arterial pressure

• Arteriole thickening reduces blood flow and causes:

  • Shrunken kidney

  • Microvascular scarring with ”granular” surface

• Hypertension may also lead to:

  • Cardiac hypertrophy (enlarged heart)

  • Atherosclerosis

  • Retinopathy

  • Strokes

Hypertensive crisis

• Rare form of hypertension, less than 5% of cases, also called Malignant Hypertension (older term)

• More acute than essential, presents as severe and rapid rise in blood pressure to greater than 180/120

• This is a Medical Emergency, need to treat ASAP, may lead to rapid kidney failure and stroke

• Very high pressures can cause hemorrhages in kidneys, brain and eyes

• Kidney shows hemorrhage from damaged vessels with “flea-bitten”/ petechial hemorrhages (very similar to severe damage in RPGN)

Diabetes

• diabetic are the largest group on dialysis and most end-stage renal disease patients are diabetics

• fluctuations in blood glucose levels damage glomerular basement membranes and blood vessels

diabetic nephropathy

• basement membrane becomes thickened and leaky

• progressive kidney disease caused by arteriosclerosis of capillaries

• increase in mesangial matrix

Nodular glomerulosclerosis (Kimmelstiel-Wilson disease)

• kidney disease specific to long standing diabetes mellitus (type 1)

• characterized by nephrotic syndrome, diffuse glomerulosclerosis and nodules of mesangial matrix

Systemic Lupus Erythematosus (SLE)

• autoimmune disorder with antibodies against nuclear antigens

• Immune complexes form and deposit in the kidney

• Between 50 and 80% of SLE patients will develop Lupus Nephritis: Nephrotic syndrome characterized by a “full house” pattern of immunofluorescence staining of glomeruli (positive staining for all antibodies and complement proteins)

• Several variants, but may cause renal failure

Amyloidosis

• amyloid is insoluble aggregates of certain types of proteins that deposit in organs/tissues and interfere with function

• deposits of amyloid in glomeruli cause a nephrotic syndrome

• size of kidney increases due to deposits

• can cause renal failure

Acute renal failure

• many causes:

  • trauma, shock, hypotension: reduces renal BF

  • acute infections/sepsis

  • acute toxicity from drugs/poisons or foods containing toxins

  • massive urinary outflow obstruction

• problems when kidneys stop functioning

  • water retention and generalized edema

  • uremia

  • electrolyte imbalance: potassium can’t be excreted, and levels increase in the blood (hyperkalemia) which can cause arrhythmias and asystole

Chronic renal failure

• AKA end stage renal disease

• Azotemia and Uremia: Uric acid crystals may deposit on the tongue or eyelids, persons may give off an odor of urine

• GI tract: Constipation, Diarrhea, Nausea and Vomiting

• CNS: Muscle weakness, Headache, Retinal Damage, Delirium, Convulsions, Coma

• Cardiovascular: Pericarditis, Anemia, Hypertension, Pulmonary Edema

• Treatment needs to start early to minimize systemic affects

• Once damage reaches a certain point, loss of function becomes

  progressive, dialysis or transplant are the only options

Kidney transplantation

• Hyperacute Rejection: Rejection is immediate due to pre-formed antibodies to endothelial cells, this usually is prevented by careful pre screening prior to transplant

• Acute Rejection: Most common type, usually occurs in first 6 months due to T cells sensitized to donor kidney antigens

• Chronic Rejection: Causes are not clear and difficult to manage and may require 2nd transplant