04 - Urinary System

nutshell-reviews presents:OSPEAnatomical PathologyUrinary System

US 103- KIDNEY - PyelonephritisInflammation affecting 1) �Renal tubules 2)Interstitium 3) Renal pelvis

EITIOPATHOGENESIS

Aetiological agents are mainly bacterial: Gram negative bacteria inhabiting the intestinal tract: E. Coli, Enterobacter, � �Proteus,Klebsiella, Strep. Faecalis.

• Usually an endogenous infection:1. Via bloodstream (haematogenous)2. Via lower urinary tract (ascending).* MORE COMMON

First step is the colonization of the distal urethra and/or introitus �by coliform bacteria �

Risk factors (ascending route):• Catheterization and other instrumentation. Much more common �

in females due to short urethra.• Patients with outflow obstruction - tumours, calculi and benign

hypertrophy.• Patients with bladder dysfunction.�• Incompetence of vesico-ureteral orifice (see below).�

Incompetence of vesico-ureteral orifice• Allows reflux of bladder urine into the ureters - called �

vesico-ureteral reflux (VUR).• Due to a congenitally short or absent intra-vesical portion �

of ureter.• Allows bacteria to ascend ureter into pelvis.�• May also enter renal parenchyma through open renal �

papillae (intra-renal reflux).

Haematogenous route is more common in:• Debilitated patients• Patients with immunosupression• Staphylococcal infection• Fungal infections

RISK FACTORS

• Obstruction - congenital or acquired.�• Instrumentation.�• Vesico-ureteric reflux.�• Pregnancy.�• Gender and age.�• Pre-existing renal lesions.�• Diabetes mellitus.�• Immunodeficiency.�

SIGNS & SYMPTOMS• Fever• Lethargy• Nausea and vomiting• Flank pain or dysuria• Hypertension

INVESTIGATION & DIAGNOSIS

IMAGING• Voiding cystourethrogram (VCUG) findings- document the reflux

of urine to the renal pelvis and ureteral dilatation • CT scans• Ultrasound- show calculi

OTHER DX TESTS• Urinalysis results may reveal pyuria. Obtain a urine culture,

which often isolates gram-negative bacteria, such as Escherichia coli or Proteus species. Proteinuria may be present Serum creatinine and blood urine nitrogen levels are elevated (azotemia).

• Renal biopsy specimens show focal glomerulosclerosis

KEY MORPHOLOGICAL FEATURES

Jar : Chronic Pyelonephritis• Chronic tubulo-interstitial inflammation and scarring associated

with calyceal and pelvic involvement.

Macroscopic:• Irregularly scarred kidneys�• Coarse deep irregular scars on the cortex are characteristic.�• Upper and lower poles most affected.�• Tubular atrophy and dilatation.�• Tubules filled with protein casts - � thyroidization.• Interstitial inflammation and fibrosis.�• May show superimposed acute infection.�• Obliterative endarteritis of arcuate and interlobular arteries.�• Hypertensive changes may also be seen.�• Fibrosis around the calyces.�• Glomeruli may be normal or diseased (peri-glomerular fibrosis, �

sclerosis)

COMPLICATIONS• 1. Papillary necrosis - seen in• Diabetics�• Urinary tract obstruction�• Usually bilateral�• Tips or distal two-thirds of the renal papillae undergo coagulative infarct �

necrosis• Often terminates in acute renal failure�• 2. Pyonephrosis - pus filling the renal pelvis, calyces and ureter.• Seen in total or near-total obstruction�• 3. Peri-nephric abscess• Extension from kidney through the renal capsule�

TREATMENT• Medical therapy with antibiotics, such as amoxicillin,

trimethoprim/sulfamethoxazole (Bactrim), trimethoprim alone, or nitrofurantoin, is usually sufficient.

MGT- 101 Benign Prostatic Hyperplasia

Prostatic hyperplasia is characterized by proliferation of both stromal and epithelial elements, with resultant enlargement of the gland and, in some cases, urinary obstruction. Common in men by the age of 40, reaching 90% by the eighth decade

PATHOGENESIS

• Most hyperplastic lesions arise in the inner transitional and central zones of the prostate, while most carcinomas (70% to 80%) arise in the peripheral zones.

• Dihydrotestosterone (DHT) through the action of 5α-reductase, and its metabolite, 3α-androstanediol, seem to be major hormonal stimuli for stromal and glandular proliferation. DHT binds to nuclear androgen receptors and, in turn, stimulates synthesis of DNA, RNA, growth factors, and other cytoplasmic proteins, leading to hyperplasia.

RISK FACTORS

• Age• Family History• Higher testosterone levels, 5-alpha-reductase activity, androgen receptor

expression, and growth factor activity.

SIGNS AND SYMPTOMS

Clinical manifestations occur in only about 10% of men with the disease. Most common are those of lower urinary tract obstruction. • Urinary frequency • Urinary urgency • Hesitancy • Incomplete bladder emptying• Straining • Decreased force of stream • DribblingThe combination of residual urine in the bladder and chronic obstruction

increases the risk of UTIs.

INVESTIGATION AND DIAGNOSIS

• Urinalysis • Urine Culture • Prostate-Specific Antigen (PSA) • Electrolytes, BUN, and Creatinine • Ultrasonography (abdominal, renal, transrectal)

• Prostate is enlarged and nodular.• The cut surface contains many fairly well-circumscribed nodules most

pronounced in the central and transitional region. • The nodules may have a solid appearance or may contain cystic spacs• The urethra is usually compressed by the hyperplastic nodules, to a slit-

like orifice.

TREATMENT• Mild-to-moderate symptoms should be managed by ‘watchful waiting’,

• Patients with moderate prostatic symptoms can be treated medically.

• Alpha-blockers such as tamsulosin.

Finasteride is a competitive inhibitor of 5α-reductase, which is the enzyme involved in the conversion of testosterone to DHT.

Finasteride decreases prostatic volume with an increase in urine flow.

KEY MORPHOLOGICAL CHANGES

US 105/118- Kidney- Nephroblastoma {Wilm’s Tumor}

Aetiopathogenesis

•Wilms' tumor usually manifests in children < 5 yr but occasionally in older children

and rarely in adults.

•Wilms' tumor accounts for about 5% of cancers in children < 15 yr.

•Bilateral synchronous tumors occur in about 5% of patients; bilateral disease is more common among very young children, especially girls.

• Rule of 5’s

US 105- Kidney- Nephroblastoma

Signs and Symptoms:

• painless, palpable abdominal mass. • abdominal pain (uncommon)• Hematuria• Fever• anorexia, nausea, and vomiting.

• Hematuria (occurring in 15 to 20%) indicates invasion of the collecting system. Hypertension may occur if compression of the renal pedicle or renal parenchyma causes ischemia.

 • Diagnosis: Abdominal ultrasonography and

CT; and a biopsy.

US 105- Kidney- NephroblastomaMorphology:

•Grossly, Wilms tumor tends to present as a large, solitary, well-circuscribed mass, although 10% are either bilateral or multicentric at the time of diagnosis.

•On cut section, the tumour is soft, homogenous, and tan to gray with occasional foci of haemorrhage, cyst formation, and necrosis.

US 105- Kidney- Nephroblastoma

Treatment: •Surgery and chemotherapy•Sometimes radiation therapy

US-106 Renal cell carcinomaRenal Cell Carcinoma are derived from the renal tubular epithelium (mainly the small tubules). Located predominantly in the cortex. Filled with accumulated lipids and carbohydrates.

Risk factors:•Smoking•Hypertension•Obesity• Occupation exposure to cadmiuim, asbestos, gasoline• Polycystic disease as a complication to chronic dialysis

•genetics

Classification:• Clear Cell Carinoma• Papillary Renal Cell Carcinoma• Chromophobe Renal Cell Carcinoma

ETIOPATHOGENESIS

•clear cell carcinoma: loss of 3p•papillary carcinoma: trisomy 7, 16, 17•chromophobe carcinoma: hypodiploid with

loss of chromosomes 1, 2, 6, 10, 13, 17, 21

MORPHOLOGY• CLEAR CELL CARCINOMA

Gross• Spherical masses 3-15cm in diameter and other smaller lesions.

May arise anywhere in the cortex

• Cut surface is yellow to orange to gray-white with prominent areas of cystic softening or of hemorrhage

• Well defined margins

Microscopic• Epithelial cells with a clear cytoplasm, well-defined

membrane and highly vascularized scanty stroma• Nuclei small and round.

GRADING:

• Grade 1: Nuclei are small (< 10µm) and round, with dense chromatin and inconspicuous nucleoli

• Grade 2: Nuclei are slightly larger (15 µm), with finely granular chromatin and small nucleoli

• Grade 3: The nuclei are 20 µm in size and may be oval in shape, with coarsely granular chromatin and prominent nucleoli

• Grade 4: The nuclei are pleomorphic, with open chromatin and single or multiple macronucleoli

PAPILLARY CELL CARCINOMAGross• Gross evidence of necrosis, hemorrhage

and cystic degeneration• Less orange to yellow due to lower lipid

content

Microscopic•Cells may have clear or pink cytoplasm

Papilla formation with fibrovascular cores. Tend to be bilateral and multiple. May show necrosis, hemorrhage and cystic degeneration however they have a lower lipid content compared to clear cell rcc.

CHROMOPHOBE TYPE CARCINOMAGross• Tan-brown colour

Microscopic• Cells have clear flocculent cytoplasm with

prominent, distinct cell membranes•Nuclei surrounded by halos of clear

cytoplasm• Large number of microvesicles

Clear flocculent cytoplasm with promient, distinct cell membranes. Nuclei surrounded by halos of clear cytoplasm.

STAGING OF RCCStage I

diameter <7 cm limited to the kidney.No lymph node involvement or metastases to distant organs.

Stage IITumor >7 cm but still limited to the kidneyNo lymph node involvement or metastases to distant organs.

Stage IIIany of the following

Tumor of any size with involvement of a nearby lymph node but no metastases to distant organs.

Tumor of this stage may be with or without spread to fatty tissue around the kidney, with or without spread into the large veins leading from the kidney to the heart.

Tumor with spread to fatty tissue around the kidney and/or spread into the large veins leading from the kidney to the heart, but without spread to any lymph nodes or other organs.

Stage IVany of the following

Tumor that has spread directly through the fatty tissue and the fascia ligament-like tissue that surrounds the kidney.

Involvement of more than one lymph node near the kidney

Involvement of any lymph node not near the kidney

Distant metastases, such as in the lungs, bone, or brain.

SIGNS and SYMPTOMS• Painless Hematuria• Loin pain• Abdominal masses• Malaise• Weight loss/anorexia• Anemia• Night sweats• Recurrent fevers

INVESTIGATIONS and DIAGNOSIS•Ultrasound•CT and MRI of kidneys

•TREATMENTo Surgical interventiono Cytoreductive surgery (esp if tumour

invades venous supply)

Sequelae of events leading to patients death

Death is due to •Venous invasion ( invades IVC and spread

hematogenously)•Lymphatic invasion •Metastases (esp to the lungs and bones ) ---

Resp failure

US 110 – Prune Belly Syndrome

There is a 21 yr old male boy in trinidad with this condition. He is the only patient in this country with the condition.

Definition and Epidemiology

Group of birth defects involving 3 main problems:

1. Poor development of abdominal muscles, causing the skin on the belly area to have a wrinkled appearance

2. Crytorchidism 3. Urinary tract deformities

Rare; affects 1 in every 40, 000 births97% Male

Risk Factors & Etiopathogenesis- Cause is unknown- Male predominance

Diagnosis/Investigations- Ultrasound: abnormally large abdominal

mass (en utero); swollen bladder, enlarged kidney (infant)

- Blood tests- CXR: oligohydramnios may cause infant to

have lung problems.

Morphology- partial/complete lack of abdominal

muscles- Cryptorchidism- Urinary tract abnormalities: large ureters,

distended bladder, ureteric colic- Frequent UTIs- Post-ejaculatory discomfort (later life)

Treatment- Surgery: muscles, testes, urinary tract- Antibiotics: for UTI’s

Prognosis- Serious and life-threatening- Most infants stillborn

Complications- Constipation- Bone deformities (funnel chest, club foot

etc)- Diseases of the urinary tract

US 114 Kidney - CalculusUrolithiasis – formation of calculus in the urinary collecting system – most often the kidney

Etiopathogenesis

• Approx. 80% of Calculi are formed of calcium oxalate alone or mixed with calcium phosphate.

• 10% Magnesium ammonium phosphate• 6-9% Uric acid or Cystine stones

• The formation of the stones are a multifactoral process however the most important cause is increased urine concetration of the stones constituents causing supersaturation and precipitation

Etiopathogenesis• Calcium stones. Most kidney stones are calcium

stones, usually in the form of calcium oxalate. Usually dietary factors.

• Struvite stones form in response to an infection, such as a uti. These stones can grow quickly and become quite large, sometimes with few symptoms.

• Uric acid stones – gout, dehydration, genetics.

• Cystine stones - hereditary disorder that causes the kidneys to excrete too much of certain amino acids (cystinuria).

Risk Factors• Family or personal history. • Age 40+• Male• Dehydration• Certain diets – (Atkins Diet)Eating a diet that's high in

protein, sodium and sugar may increase your risk of some types of kidney stones.

• Obesity • Digestive diseases and surgery - Gastric bypass surgery,

inflammatory bowel disease (Chron’s Disease) or chronic diarrhea

• Other medical conditions: renal tubular acidosis, cystinuria, primary hyperoxaluria, hyperparathyroidism, gout, certain medications (Vit C and Calcium Supplements) and some urinary tract infections (Proteus vulgaris and Stapylococci)

Signs and Symptoms

•Colicky, loin to groin pain•dysuria•hematuria•Cloudy or foul-smelling urine•Nausea and vomiting•Urinary urgency, frequency•Fever and chills if an infection is present

Investigations

•Cbc/diff, urea/electrolytes, RFT

•Urinalysis (MSU, 24 hr collection)

•Imaging – Ultrasound, CT, IV pyelography

Key Morphological Changes• Stones are unilateral in 80% of patients.

• Common sites of formation are renal pelves and calyces and the bladder.

• Occasionally, progressive accretion of salts leads to the development of branching structures known as staghorn calculi, which create a cast of the renal pelvis and calyceal system.

• These massive stones are usually composed of Magnesium ammonium phosphate (Struvite) whose formation are due to UTIs.

Complications

•Renal Colic•Recurring Stones•Increased risk of UTI•Pain•Sepsis•Bleeding

Treatment• Pain management – Opiods if necessary• Small Stones

▫ Drink water, Pain relievers, Alpha blockers (relaxes muscles in ureter)

• Large Stones▫ extracorporeal shock wave lithotripsy – use of ultrasound to

breakdown stone▫ percutaneous nephrolithotomy - surgically removing a kidney stone

using small telescopes and instruments inserted through a small incision in your back.

▫ Ureteroscope - involves passing a long, thin telescope, called a ureteroscope, through your urethra

▫ Open Surgery – Very Rare <1%▫ Parathyroid gland surgery

• Uric Acid Stones▫ Drink water, Medication to create alkaline urine

Complications

•Hypertension•Hypercalcemia•Polycythemia•Liver problems•Metastasis of cancer

Treatment

•Nephrectomy•Chemotherapy•Multi-kinase inhibitor treatment•IL Therapy•Laparoscopic Nephrectomy•Antineoplastic agents eg. Vinblastine

The Class of MBBS 2015 UWI St. Augustine has always reached for excellence through unity and a shared experience. As such a few members have gotten together to assist in the studying process for third year OSPE. Within these files are basic summaries of the anatomical pathology specimens we were required to learn. We hope that through our research we may aid in the building up both the members of our class and the future classes to come.

Special thanks goes out to: Arvinash ramdeen, Amrita Mahabir, Kiran Maharaj, Aarti Maharaj, Deandrea Rigby, Jasmin Mortimer, Javardo McIntosh, Jamico Thompson, Derwin Johnson, Rodlyn Malcolm, Alethia Lewis, Kenville Lockhart, Aaron Haralsingh, Phaedra Rampersad, Kishron Richards, Monique Adrienne Monplaisir, Cathy Martindale and Sasha Gardiner (not a medical student but a friend who research and gave aid when needed) for their research and organization of the information.

Quoting two inspirational men,

"A successful man is one who can lay a firm foundation with the bricks others have thrown at him." David Brinkley&"Life is a grindstone. Whether it grinds us down or polishes us up depends on us." -- Thomas L. Holdcroft

And I will say let us take the bricks that Uwi throws at us and the grindstone of Medical school and become the polished doctors within each of us.

Class of 2015