INTRODUCTION TO UROLOGY

INTRODUCTION TO UROLOGY

  • Instructor: Nicki Reed BVM&S CertVR DSAM (Feline) DipECVIM-CA FRCVS

    • RCVS Recognized Specialist in Feline Medicine

    • EBVS®

      Recognized Specialist in Internal Medicine

MODULE LEARNING OBJECTIVES

  • Use information in the history/physical examination to:

    • Localize the problem to the urinary system

    • Upper urinary tract

    • Lower urinary tract

    • Construct a differential diagnosis list for the identified problem(s).

    • Choose appropriate diagnostic tests and understand their interpretation.

    • Formulate appropriate treatment plans for common urinary tract conditions.

LECTURE LEARNING OBJECTIVES

  • Understand renal physiology including:

    • How blood is filtered to produce urine.

    • Hormonal input into renal function.

    • Identify abnormal glomerular filtration rate (GFR).

    • Understand factors affecting azotemia.

    • Identify causes of proteinuria and investigate this condition.

    • Identify causes of pigmenturia and investigate this condition.

    • Understand renal diagnostic tests:

    • What they show.

    • Their limitations.

URINARY SYSTEM
ANATOMY

  • Upper Urinary Tract:

    • Right kidney

    • Left kidney

    • Right ureter

    • Left ureter

  • Lower Urinary Tract:

    • Urinary bladder

    • Urethra

    • Prostate

    • Body of uterus

    • External iliac artery and vein

    • Deep circumflex iliac artery and vein

    • Broad ligament (mesometrium)

    • Ovarian artery and vein

    • Ureteral orifice

    • Vestourethral junction

    • Round ligament of uterus

FUNCTIONS OF THE KIDNEY

  • Regulates:

    • Fluid Balance

    • Acid-Base Balance

    • Electrolyte Balance

    • Excretion of waste products

    • Filtration and reabsorption

    • Blood Pressure Control

    • Calcium Homeostasis

    • Phosphate Regulation

    • Red Blood Cell Production

  • Concentration of urine involves various substances, including:

    • H+, NH3, and HCO3

    • K+, Na+, Cl-, PO4²-, urea, creatinine

    • Glucose, proteins

    • Hormonal influences:

    • Renin-Angiotensin-Aldosterone System (RAAS)

    • Parathyroid Hormone (PTH)

    • Calcitriol

    • FGF23

    • Erythropoietin

FUNCTIONS OF THE URINARY TRACT

  • Structures involved and their roles:

    • Ureters: Transport urine to the bladder, peristalsis reduces the risk of ascending infections.

    • Bladder: Stores urine until voiding.

    • Urethra: Contributes to urinary continence and helps prevent ascending infections into the bladder.

RECAP ON RENAL PHYSIOLOGY
THE NEPHRON

  • Functional unit of the kidney; approximately 800,000 to 1,000,000 nephrons per kidney.

  • Nephrons cannot regenerate.

  • Key components:

    • Glomerulus: Filters blood and produces protein-free filtrate in Bowman's space.

    • Renal Tubules: Involved in absorption and secretion of substances.

GLOMERULUS

  • Glomerular filtration rate (GFR) is impacted by blood flow.

    • Decreased blood flow leads to decreased GFR.

    • Normal GFR values:

    • Dogs: 3.5-4.5 ml/kg/min

    • Cats: 2.5-3.5 ml/kg/min

  • The glomerular basement membrane and tight junctions between podocytes normally prevent significant protein (albumin) leakage into filtrate.

    • Damage can lead to proteinuria by allowing proteins to pass into the tubular filtrate.

    • Increased pressure across the glomerulus can compound protein leakage.

PROXIMAL CONVOLUTED TUBULE REABSORPTION
Substances Reabsorbed

  • 65-70% of water

  • 65-70% of sodium chloride (NaCl)

  • 99% of glucose via Sodium-Glucose Transporters (SGLT)

  • 66% of potassium

  • 80-90% of phosphate

  • 90% of calcium

  • 99% of bicarbonate

  • 99% of amino acids

Freely Filtered Substances

  • Creatinine

  • Bilirubin in cats

Secretion

  • Hydrogen ions

  • Potassium

  • Ammonia

  • Bilirubin

  • Some secretion in dogs

LOOP OF HENLE
Descending Limb

  • Permeable to water and NaCl.

  • Water reabsorption increases the osmolality of filtrate.

Ascending Limb

  • Contains the NaKCl₂ transporter that leads to reabsorption of electrolytes.

  • Impermeable to water.

DISTAL CONVOLUTED TUBULE

  • Principal Cells: Reabsorb Na+ and water.

  • Intercalated Cells:

    • Type A: Secretes H+ ions and reabsorbs HCO3.

    • Type B: Secretes HCO3 and reabsorbs H+ ions.

  • Primary control site for acid-base balance through proton secretion.

COLLECTING DUCT
Water Reabsorption

  • Permeability to water is influenced by antidiuretic hormone (ADH).

  • ADH enhances water reabsorption by stimulating the formation of aquaporin water channels.

Urea Reabsorption

  • Urea is reabsorbed via active transporters, up-regulated in the presence of ADH.

JUXTA-GLOMERULAR APPARATUS
Macula Densa

  • Specialized cells at the junction of the thick ascending limb of the Loop of Henle (LOH) and the distal convoluted tubule (DCT)

  • Senses NaCl concentration in the filtrate.

Juxtaglomerular Cells

  • Granular cells that secrete renin in response to changes in blood flow and pressure.

Mesangial Cells

  • Located between afferent and efferent arterioles; control vessel tone.

GLOMERULAR FILTRATION RATE (GFR)
Influencing Factors

  • Renal Blood Flow: Higher blood flow increases GFR.

  • Blood volume and atrial pressure: Increased atrial pressure affects GFR through hormone secretion (e.g., atrial natriuretic peptide).

  • Blood pressure relationship:

    • Higher blood pressure leads to higher GFR, but excessive can cause protein loss.

    • Lower blood pressure leads to lower GFR and potential ischemic damage to nephron.

AUTOREGULATION
Kidney Regulation

  • The kidneys regulate blood flow and pressure locally to maintain steady GFR.

    • Myogenic reflex: Dilation of afferent arteriole (AA) results in smooth muscle contraction.

    • Macula Densa: Senses increased Na delivery and blood flow; causes AA constriction via mesangial cells.

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)

  • Components:

    • Low blood pressure or sympathetic stimulation triggers renin release.

    • Renin cleaves angiotensinogen to form angiotensin I; subsequently converted to angiotensin II by the Angiotensin-Converting Enzyme (ACE).

    • Angiotensin II leads to increased Na+ reabsorption in the proximal tubule and vasoconstriction.

    • Aldosterone further increases Na+ reabsorption in the distal tubule, ultimately raising blood pressure.

CALCIUM HOMEOSTASIS
Hormonal Regulation

  • Parathyroid Hormone (PTH):

    • Increases the activity of 1α Hydroxylase, enhancing calcium reabsorption and reducing phosphate reabsorption.

  • 1α Hydroxylase: Converts 25(OH) Vitamin D3 (calcidiol) to 1,25(OH)2 Cholecalciferol (calcitriol).

  • Calcitriol:

    • Enhances calcium and phosphate absorption in bone, kidney, and gut.

    • Reduces synthesis and secretion of PTH.

PHOSPHATE REGULATION

  • Majority reabsorbed in the proximal convoluted tubule via sodium-phosphate co-transporters.

  • Calcitriol enhances reabsorption, while PTH and FGF23 inhibit it.

ERYTHROPOIETIN

  • Erythropoietin (EPO) is produced in peritubular renal cells.

  • Stimulates the differentiation of normoblasts to mature red blood cells in bone marrow.

  • Production is controlled by hypoxia-inducible factor (HIF); in hypoxemia, there is an increase in EPO production due to inhibition of HIF prolyl-hydroxylase (HIF-PH).

URINE ANALYSIS
Urine Collection Methods

Free Catch

  • Hydrophobic cat litter or canine collection device:

    • Cheapest method, good for screening (concentration, presence of blood or protein, but not sterile).

Catheterisation

  • Relatively straightforward for male dogs; may necessitate sedation for females or cats.

  • Requires aseptic technique to prevent infection.

Cystocentesis

  • Sample collected directly from the bladder; ideal for culture.

  • May pose challenges in large dogs or obese patients; ultrasound guidance may be beneficial.

  • Risks include trauma, bleeding, and seeding of neoplastic cells.

URINE ANALYSIS - TIMELY ANALYSIS

  • Should be conducted as soon as possible after sampling due to:

    • Potential for renal casts to disperse.

    • Red blood cells may hemolyze, releasing hemoglobin.

    • Crystals can precipitate.

  • Always warm refrigerated samples to room temperature before testing, as temperature affects color pad accuracy on dipsticks.

URINE ANALYSIS - VISUAL ASSESSMENT

  • Normal Urine Appearance:

    • Color: Straw yellow and clear.

    • Pale urine suggests dilute urine with low specific gravity.

    • Turbid urine indicates inflammation or crystal presence.

  • Pigmenturia:

    • Complicates color interpretation on dipstick; forms include:

    • Hematuria: Blood present.

    • Hemoglobinuria: Hemoglobin present.

    • Bilirubinuria: Bilirubin present.

PIGMENTURIA
Sample Analysis

  • Centrifuge the sample to analyze the supernatant coloration.

    • If supernatant is pink:

    • Indicates hematuria.

    • If supernatant is yellow/green:

    • Indicates hemoglobinuria.

    • Requires further evaluation to check for metrics like CK levels for myoglobinuria.

URINE ANALYSIS - SPECIFIC GRAVITY

  • Indicates urine concentration levels; measured using a refractometer.

  • Normal Ranges:

    • Dog: 1.015-1.035

    • Cat: 1.030-1.040

  • Effects of Diet:

    • Animals on dry diets exhibit higher USG than those on wet diets.

USG Levels Interpretation

  • Hyposthenuria:

    • Urine is actively diluted, with USG < 1.008 (indicative of conditions like diabetes insipidus).

  • Isosthenuria:

    • Urine osmolality equal to plasma, with USG between 1.008-1.012 (often suggestive of renal tubular disease).

  • Hypersthenuria:

    • Urine more concentrated than plasma, with USG > 1.012 (may be normal or indicate dehydration).

URINE ANALYSIS - DIPSTICK USE
Useful Indicators

  • Glucose

  • Ketones

  • Bilirubin

  • Blood

  • pH (while a pH meter is more accurate, normal pH is 5.0-7.0)

Not Useful Indicators

  • Specific Gravity (use refractometer).

  • Leucocytes designed to detect human leucocytes; false positives are especially common in cats.

  • Urobilinogen & Nitrite are not reliable.

URINE ANALYSIS - GLUCOSURIA
Causes

  • High Blood Glucose:

    • Renal threshold for tubular reabsorption is:

    • Dogs: 12 mmol/l

    • Cats: 16 mmol/l

    • Causes include diabetes mellitus or stress-induced hyperglycemia.

  • Normal Blood Glucose:

    • Conditions include primary renal glucosuria, Fanconi syndrome, copper hepatopathy in Labradors, acute kidney injury, or infections like pyelonephritis and leptospirosis.

  • Spurious Causes:

    • Contamination or drugs (e.g., cefalexins, amoxicillin, enrofloxacin) can yield false results.

URINE ANALYSIS - KETONES
Measurement and Conditions

  • Dipsticks primarily measure acetoacetate; beta-OH butyrate is more prominent and can be measured by ketone meter.

    • Conditions leading to elevated ketones include diabetic ketoacidosis, hepatic lipidosis, and starvation.

  • Ketone sensitivity and specificity in urine vs. plasma measured shows overall differences; for example, urine sensitivity is 82% with a specificity of 95%.

URINE ANALYSIS - BILIRUBIN
Interpretation

  • Normal for dogs, especially in males with concentrated urine.

  • Always abnormal in cats associated with hyperbilirubinemia.

  • Blood Presence on Dipstick:

    • Dipstick cannot differentiate between blood, hemoglobin, or myoglobin; solid colors indicate significant presence while 'spotting' may be more nuanced.

URINE ANALYSIS - PROTEIN
Reliability and Measurement

  • Dipsticks can be unreliable for detecting protein in dilute samples; they serve as a semi-quantitative method.

  • Quantification can be accomplished through urine protein:creatinine ratio (UPCR).

  • Even in proteinuria, the presence can be influenced by inflammation or blood within the urine.

PROTEINURIA
Classifications

  • Pre-Renal Causes:

    • Hypertension, physiological factors (exercise, excitement, heat stress), hyperglobulinemia, neoplasia, infection, drug effects (e.g., steroids).

  • Renal Causes:

    • Glomerular disease with UPC typically > 2.0; tubular diseases with UPC between 0.4-2.0.

  • Post-Renal Causes:

    • Hematuria, urinary tract infection, urethritis, prostatitis.

URINE ANALYSIS - SEDIMENT
Components to Analyze

  • Renal casts indicating tubular damage, may ‘disappear’ during transit to the lab.

  • White blood cells as indicators of inflammation.

  • Red blood cells indicating hematuria vs. hemoglobinuria.

  • Crystals and bacteria, with submissions for culture recommended.

  • Wet preparations should differentiate fat droplets from bacteria, and staining (e.g., Romanowsky stain) increases sensitivity for bacteria identification.

URINE ANALYSIS - CYSTATIN B

  • Cystatin B is a small intracellular protein released into urine upon tubular cell damage.

  • Increased urinary levels suggest ongoing renal tubular damage.

TERMINOLOGY

  • Azotemia: Increased nitrogenous waste products in the blood.

  • Uremia: Clinical syndrome associated with the consequences of azotemia.

  • Hyposthenuria: Urine is more dilute than plasma (USG < 1.008).

  • Isosthenuria: Urine is iso-osmolar to plasma (USG between 1.008-1.012).

  • Hypersthenuria: Urine is more concentrated than plasma (USG > 1.012).

FACTS AND FIGURES
Water Intake and Output

  • Water Intake:

    • Dogs: 40-60 ml/kg/day

    • Cats: 20-40 ml/kg/day

  • Urine Output:

    • General: 1-2 ml/kg/hr

    • Conditions of polydipsia:

    • Dogs: > 100 ml/kg/day

    • Cats: > 80 ml/kg/day

    • Oliguria: Urine output (0.5-1 ml/kg/hr)

    • Anuria: Urine output < 0.5 ml/kg/hr

Specific Values

  • Urine Specific Gravity:

    • Dogs: 1.015-1.035

    • Cats: 1.030-1.040

  • Urine Protein:Creatinine Ratio:

    • Cats: Normal < 0.2; Borderline 0.2-0.4; Proteinuria > 0.4

    • Dogs: Normal < 0.2; Borderline 0.2-0.5; Proteinuria > 0.5

GFR and Blood Pressure

  • Normal GFR:

    • Dogs: 3.5-4.5 ml/kg/min

    • Cats: 2.5-3.5 ml/kg/min

  • Blood Pressure:

    • Systolic: 100-150 mmHg

    • Mean: > 60 mmHg

  • Urea Levels:

    • Dogs: 8-25 mg/dl

    • Cats: 15-35 mg/dl

  • Creatinine Levels:

    • Dogs: < 1.6 mg/dl

    • Cats: < 2.3 mg/dl

  • SDMA Levels: < 15 µg/dl

SUMMARY

  • The kidneys have multiple critical functions that can result in a spectrum of abnormal findings.

  • Assessment of renal function typically involves blood tests and urine analysis; this may be supplemented by blood pressure measurement and diagnostic imaging techniques.