Renal Pathology 1: Calculi, Obstruction, Anatomy

• Renal Pathology 1 covers renal calculi, congenital abnormalities, and pathology of urinary tract obstruction.

Renal Pathology Overview

• Pathology is a clinical specialty that takes a team approach to patient care.
• It involves determining the cause of a disease for accurate diagnosis.
• Pathology also informs management, treatment, and prognosis.

Kidney Anatomy

• The normal kidney weighs 130-150 grams.
• It accounts for 1/200 of the body weight and receives 20-25% of every heartbeat's output.
• The kidney regulates fluids/electrolytes, similar to the lungs' role with air/gases.
• Kidneys are involved in blood pressure control, erythropoietin production, and drug metabolism.
• Kidney failure can result in hypertensive heart disease and concentric left ventricular hypertrophy (LVH), a common cause of death in chronic kidney disease (CKD).

Kidney Blood Supply

• A highly vascular organ with an end arterial system.
• Resistance vessels and peritubular capillaries drain into the venous system.
• The blood vessels include arteries, afferent and efferent arterioles, peritubular capillaries, and veins.

Glomerulus Components

• Mesangial cells
• Mesangial matrix
• Endothelial cells
• Visceral epithelial cells

Filter Membrane

• The hydrostatic pressure from the vascular side is 50-60mm mercury.
• There is a one-way flow across the membrane to the urinary side.
• Pathology at the endothelial side results in inflammation, while pathology at the epithelial side does not elicit an inflammatory reaction.

Kidney Anatomy - Tubules

• Proximal cortical tubules
• Loop of Henle
• Juxtaglomerular apparatus (JGA)
• Distal collecting ducts

Renal Tubules

• Proximal tubules are metabolically active due to numerous mitochondria, making them prone to ischaemic injury.
• Distal tubules have fewer mitochondria, are less metabolically active, and primarily handle fluid and electrolyte transfer.
• Red granules in proximal tubules are packed mitochondria.

Interstitium

• It is normally inconspicuous and contains peritubular capillaries.
• Fibrosis in the interstitium is a marker of prognosis in chronic kidney diseases.

Hydronephrosis

• Defined by the dilation of the renal pelvis and calyces.
• It also involves the flattening of the papillae and atrophy of the renal cortex.
• Unilateral hydronephrosis can lead to kidney loss and raised blood pressure.
• Bilateral hydronephrosis necessitates correction to prevent death.

Hydronephrosis Causes

• Congenital causes include pelviureteric junction (PUJ) obstruction.
• Acquired causes stem from the urethra to the kidney, including tumors, calculi, or other obstructions.
• Other obstructions include issues within the lumen, the wall, or external to the urinary tract.

Renal Calculi (Kidney Stones)

• The stones affect 5-10% of people in the Western world during their lifetime.
• Men are more prone to kidney stones than women, and they commonly occur in the 20s-30s age range.
• Classified by formation in the kidney or bladder.
• They can cause ureteric colic and vary in size.
• Clinical features include renal colic (severe pain), hematuria, pyelonephritis, and hydronephrosis.
• Treatment options include lithotripsy

Renal Calculi Composition

• 70% are calcium-based (phosphate or oxalate, commonly)
• 5-10% are magnesium ammonium phosphate (struvite) linked with infections.
• 5-10% are uric acid, often associated with gout and are radiolucent.
• 1-2% are cystine, uncommon, and seen in children with cystinosis.
• About 5% are of unknown types.

Renal Calculi Pathogenesis

• 90% of renal calculi are calcium-containing and radio-opaque.
• Hypercalciuria (50%+) with normal serum calcium is common; only 2-3% present along with hypercalcemia.
• Struvite calculi have infection as the nidus (staghorn).
• Uric and cystine: raised levels
• Oxalate stones occur with malabsorption syndromes or ethylene glycol (anti-freeze) ingestion.

Congenital Anomalies

• Bilateral renal agenesis leads to Potter syndrome.
• Unilateral renal agenesis.
• Horseshoe kidney
• Hypoplasia
• Ectopia
• Dysplastic kidney

Cystic Diseases Types

• Inherited and Acquired
• Inherited forms include Autosomal Dominant Polycystic Kidney Disease (A.D.P.K.D.)

Autosomal Dominant Polycystic Kidney Disease (A.D.P.K.D.)

• The most common inherited cystic kidney disease occurring in 1 in 500 to 1 in 1000 births.
• It represents the 4th leading cause of CKD; it affects 5-10% of dialysis patients.
• It typically presents in the 30s-50s.
• 90% is linked to chromosome 16 (PKD1, PKD2).
• 10% is linked to chromosome 4.
• It is associated with cell proliferation leading to renal cell carcinoma.

Autosomal Recessive Polycystic Kidney Disease (A.R.P.K.D.)

• Rare, occurring in 1 in 20,000 births.
• Related to the PCKD1 gene location on Chromosome 6P12.
• Often has a poor prognosis, and cysts radiate from the cortex to the medulla.

Other Cystic Diseases – Inherited

• Nephronophthisis (AR)
• Medullary cystic disease (AD)
• Cytogenetic abnormalities, proliferative processes, and ADPKD are most important.

Cysts and Cancer

• Cysts lead to a predisposition to cancer, across all cystic types and causes.
• Renal cell carcinoma is a specific risk.

Von Hippel-Lindau Syndrome

• It is an uncommon, autosomal dominant condition.
• It presents with kidney cysts, also in the pancreas and epididymis.
• Also haemangioblastomas of the retina, cerebellum, and spine.
• The syndrome is linked to chromosome 3p25.
• 50% of patients develop renal cell carcinoma (RCC).
• Treatment includes prophylactic bilateral nephrectomy.

Simple Cysts

• Very common and are often age-related.
• Ischaemia secondary to vascular diseases.
• Fibrosis leads to tubule obstruction and cyst formation.
• Cystic lesions are assessed via imaging to determine follow-up or resection needs.

Renal Diseases Classification

• Renal diseases can divided into "surgical" and "medical" categories

Surgical Kidney Diseases

• Tumours
• Calculi
• Obstructing lesions whether congenital or acquired.

Medical Renal Diseases' Clinical Presentations

• Haematuria (blood in urine).
• Nephrotic syndrome (abundant protein in the urine).
• Acute Renal Failure (ARF).
• Nephritic Syndrome – Acute.
• Chronic Renal Failure.