Urinalysis and Body Fluids Overview

Urinalysis and Body Fluids Study Notes

Chapter 3: Renal Anatomy, Physiology, and Function Testing

Nephrons

  • Definition: Functional unit of the kidney.

  • Quantity: Approximately 1 to 1.5 million nephrons per kidney.

  • Types:

    • Cortical Nephrons (85% of total nephrons)

    • Function: Removal of waste products and reabsorption of filtered nutrients.

    • Juxtamedullary Nephrons

    • Feature: Longer loops of Henle, contributing to urine concentration.

Nephron Functions

  • Key Processes:

    • Renal Blood Flow: Circulation within the kidney.

    • Glomerular Filtration: Process of filtering blood through the glomeruli.

    • Tubular Reabsorption: Returning substances from filtrate back to blood.

    • Tubular Secretion: Adding substances from blood to the filtrate.

Renal Blood Flow

  • Pathway:

    • Afferent Arteriole: Blood enters the glomerulus.

    • Efferent Arteriole: Blood exits the glomerulus.

    • Peritubular Capillaries: Associated with the proximal and distal convoluted tubules.

    • Vasa Recta: Associated with the loops of Henle.

    • Renal Vein: Blood exits the kidney.

Renal Plasma Flow

  • General Flow:

    • Renal Blood Flow: Approximately 1200 mL/min.

    • Renal Plasma Flow: Approximately 600-700 mL/min.

Glomerular Filtration

  • Glomerulus Structure:

    • Composed of a tuft of eight capillary lobes located in Bowman’s capsule.

  • Filtration Properties:

    • Nonselective filtration: Allows passage of substances less than 70,000 molecular weight (MW).

    • Influenced by hydrostatic and oncotic pressures within Bowman’s capsule and glomerulus.

  • Regulatory System: Renin-angiotensin-aldosterone system (RAAS).

Cellular Structure of the Glomerulus

  • Composed of three layers:

    • Endothelial Cells: Fenestrated, allowing small molecules through while blocking larger ones.

    • Basement Membrane: Further restricts the passage of large molecules.

    • Visceral Epithelium (Podocytes): Intertwining podocytes have filtration slits that allow selective filtering of substances.

Filtration Pressure Regulation

  • Mechanism:

    • Regulation of arteriole size maintains consistent glomerular pressure.

    • Under low systemic blood pressure: Afferent arteriole dilates and efferent arteriole constricts to prevent decreased glomerular blood flow.

    • Under high systemic blood pressure: Afferent arteriole constricts to prevent overfiltration and glomerular damage.

Renin-Angiotensin-Aldosterone System (RAAS)

  • Function: Regulates blood flow to and within the glomerulus, responding to changes in blood pressure and plasma sodium levels.

  • Components:

    • Juxtaglomerular Apparatus: Contains juxtaglomerular cells in the afferent arteriole and macula densa in the distal convoluted tubule (DCT).

    • RAAS Initiation: Macula densa cells detect changes in blood pressure, leading to renin secretion.

RAAS Cascade

  • Process:

    • Renin from juxtaglomerular cells acts on Angiotensinogen to form Angiotensin I.

    • Angiotensin I is converted to Angiotensin II in the lungs via Angiotensin-Converting Enzyme (ACE).

Functions of Angiotensin II

  • Actions:

    • Dilates afferent arterioles, constricts efferent arterioles.

    • Stimulates sodium reabsorption in proximal convoluted tubule (PCT).

    • Triggers release of aldosterone to enhance sodium reabsorption in DCT and collecting duct (CD), and increases potassium excretion.

    • Stimulates release of antidiuretic hormone (ADH) to aid in water reabsorption in DCT and CD.

Glomerular Filtrate Characteristics

  • Normal Rate of Filtration: Approximately 120 mL/min.

  • Composition: Similar to plasma but devoid of plasma proteins, protein-bound substances, and cells. Ultrafiltrate specific gravity averages 1.010.

Tubular Reabsorption

  • Mechanisms:

    • Active Transport: Requires cellular energy; substances like glucose, salts (particularly sodium), and amino acids reabsorbed in PCT, chloride in ascending loop of Henle, sodium in DCT.

    • Passive Transport: Occurs based on concentration gradients; water reabsorption happens throughout nephron, except in ascending loop of Henle.

  • Example Substances: Urea in PCT and ascending loop of Henle, sodium in ascending loop of Henle.

Maximal Reabsorptive Capacity (Tm)

  • Definition: The plasma level at which active transport ceases.

  • Renal Threshold: Plasma level causing the saturation of active transport, leading to substances appearing in urine.

  • Glucose Threshold: 160-180 mg/dL; above this, glucose appears in urine, indicating possible tubular damage.

Tubular Concentration

  • Descending Loop of Henle: Passive reabsorption of water into medulla.

  • Ascending Loop of Henle: Impermeable to water; actively reabsorbs chloride and passively reabsorbs sodium.

  • Countercurrent Mechanism: Maintains osmotic gradient in the medulla; sodium and chloride are sequentially reabsorbed from filtrate, and water follows in descending loop.

Collecting Duct Reabsorption

  • Final Filtrate Concentration: Begins in late DCT and continues into CD; controlled by ADH based on body hydration levels.

  • ADH Function: Modulates permeability of DCT and CD walls to water; lower ADH levels lead to higher urine volume and vice versa.

Tubular Secretion

  • Functions:

    • Reabsorption: Filtrate to blood.

    • Secretion: Blood to filtrate, eliminating non-filtered wastes and regulating acid-base balance:

    • Secretion of H+ ions and bicarbonate regulation.

    • Control of hydrogen ion levels, potentially excreting excess H+ ions as associated with phosphate or ammonia.

Ammonia and Bicarbonate Dynamics

  • Ammonia (NH3): Secreted by DCT, forming ammonium (NH4+) which remains in filtrate and cannot be reabsorbed.

  • Bicarbonate (HCO3-): While H+ is secreted, filtered bicarbonate is returned to the plasma, preventing excess excretion.

Renal Function Tests

  • Purpose: Assess glomerular filtration, tubular reabsorption, tubular secretion, and renal blood flow.

  • Key Tests Include:

    • Clearance Tests

    • Osmolarity Testing

    • Ammonia and titratable acidity tests.

Glomerular Filtration Clearance Tests

  • Function: Measure the efficiency of kidneys in filtering blood substances that cannot be reabsorbed or secreted.

  • Conditions: Requires accurate timing and consistency in plasma substance levels for reliable results.

Evaluated Substances in Clearance Tests

  • Traditional: Urea (historically, not used anymore due to partial reabsorption), Inulin (ideal but requires infusion), Creatinine (most common, waste product of muscle), Beta2 microglobulin, Cystatin C, Radioisotopes.

Creatinine Clearance Test

  • Rationale: Reflects glomerular filtration rate (GFR).

  • Procedure: Requires timed urine volume and respective creatinine levels from blood and urine.

  • Important Considerations: Factors such as muscle mass (men typically producing more due to higher muscle destruction) influence normal values.

Calculated GFR Formulas

  • Cockcroft-Gault Formula: C_{cr} = \frac{(140 - age)(weight \text{ in kg})}{72 \times serum \text{ creatinine in mg/dL}}

    • Adjustments: Result multiplied by 0.85 for women.

Modification of Diet in Renal Disease (MDRD) Formula

  • Parameters: Does not require weight; relies on serum BUN, serum albumin, and ethnicity.

    • Sample formula:
      GFR = 170 \times plasma \text{ creatinine}^{-0.999} \times age^{-0.176} \times 0.822 \text{ (if female)} \times 1.1880 \text{ (if black)} \times BUN^{-0.170} \times serum \text{ albumin}^{+0.318}

Substances Not Requiring Urine Collection

  • Small Proteins:

    • Beta2 microglobulin: Indicator of renal function, sensitive but unreliable in certain diseases.

    • Cystatin C: Reflects GFR and can monitor various patient types effectively.

    • Radioisotopes: Used for visual assessment and measuring plasma disappearance rates.

Tubular Reabsorption Tests

  • Function: Indicators of early renal diseases and measuring renal concentrating ability.

  • Standard Baseline: 1.010 specific gravity of ultrafiltrate for accurate assessments.

Osmolarity Testing

  • Note: Considered superior to specific gravity as it evaluates renal concentration ability focusing only on small molecules.

  • Clinical Unit: Expressed in milliosmoles (mOsm).

Colligative Properties and Osmometry

  • Definition: Properties related to the number of solute particles in a solvent affecting freezing point, boiling point, osmotic pressure, and vapor pressure.

  • Measurement Methods:

    • Freezing Point Osmometers: Measures the depression of the freezing point of a solution.

    • Vapor Pressure Osmometers: Measures dew point, where water vapor condenses.

Clinical Significance of Renal Testing

  • Applications: Evaluates renal concentrating ability, monitors renal diseases, and facilitates differential diagnoses of various states of hydration (hypernatremia and hyponatremia).

Normal Values for Osmolarity

  • Serum: 275-300 mOsm.

  • Urine: Varies based on hydration, ranging from 50-1400 mOsm.

Diabetes Insipidus and Free Water Clearance

  • Condition: Results from decreased ADH production or tubule insensitivity to ADH.

  • Clearance Formula:
    C{osm} = \frac{U{osm} \times V}{P_{osm}}

  • Free Water Clearance: Calculated as V - $C_{osm}$, with results indicating hydration status.

Tubular Secretion and Renal Blood Flow Relationship

  • Interdependence: Adequate blood flow is necessary for effective secretion assessment, while sufficient secretion validates blood flow metrics.

PAH Clearance for Renal Blood Flow

  • Function: PAH is secreted in the proximal convoluted tubule and is crucial for measuring effective renal plasma flow; expected values are 600-700 mL/min for normal functioning.