Urinary System and Renal Physiology

Overview and Functions of the Urinary System

• Waste Removal:
  • The primary function is the removal of metabolic nitrogenous wastes.
  • Key examples include Urea, Uric acid, and Creatinine.
  • Medical measurement is via Blood Urea Nitrogen (BUN).
    • Normal BUN range: $10 - 20\,mg/dL$.
    • Azotemia: A state of high BUN indicating renal insufficiency.
    • Uremia: Extremely high blood urea levels indicating kidney failure; requiring treatment via hemodialysis or organ transplant.
• Regulation of Blood Pressure and Volume:
  • Managed through water regulation and the secretion of the enzyme Renin.
• Endocrine and Production Functions:
  • Erythropoietin: A hormone produced by the kidneys that stimulates the production of erythrocytes (red blood cells).
  • Calcium Level Regulation: The kidneys produce Calcitriol to increase circulating calcium levels.
• Homeostatic Regulation:
  • Maintains blood gases and pH through the balance of Hydrogen ($H^+$), Bicarbonate ($HCO_3^-$), and various electrolytes.
• Organs and Anatomy:
  • Two Kidneys: Situated posteriorly and retroperitoneally. The right kidney sits lower than the left due to the liver.
  • Two Ureters: Connect the kidneys to the bladder.
  • One Urinary Bladder: Storage site for urine.
  • One Urethra: Exit path for urine.

Anatomy of the Kidney and Blood Supply

• External Anatomy:
  • Fibrous Capsule: The outer protective layer.
• Internal Structures:
  • Renal Cortex: The outer layer.
  • Renal Medulla: The inner layer, composed of Renal Pyramids and Renal Columns.
  • Renal Columns: Cortical extensions between the pyramids.
  • Renal Papilla: The tip of the pyramid where urine exits.
  • Renal Sinus: An internal cavity containing vessels and collecting structures.
  • Collecting Structures: Minor calyx, Major calyx, and the Renal pelvis (leads to the ureter).
• Blood Flow Through the Kidney:
  • Aorta $\rightarrow$ Renal artery $\rightarrow$ Arcuate artery $\rightarrow$ Cortical radiate artery $\rightarrow$ Afferent arteriole $\rightarrow$ Glomerulus $\rightarrow$ Efferent arteriole $\rightarrow$ Peritubular capillaries (cortex) or Vasa recta (medulla) $\rightarrow$ Cortical radiate vein $\rightarrow$ Arcuate vein $\rightarrow$ Renal vein $\rightarrow$ Inferior vena cava.
• Nephron Distribution: Each kidney contain over $1.2 \times 10^6$ nephrons located across the cortex and medulla.

The Nephron: Structures and Filtrate Flow

• The Nephron is the functional unit of the kidney, consisting of two main parts:
  1. Renal Corpuscle: Filters blood plasma.
     • Afferent Arteriole: Supplies blood to the nephron; notably larger than the efferent arteriole.
     • Glomerulus: The capillary network within the capsule where filtration occurs.
     • Efferent Arteriole: Drains blood from the glomerulus ($\text{E}$ for exiting).
  2. Renal Tubule: Converts filtrate into urine.
     • Proximal Convoluted Tubule (PCT): The longest and most coiled section; primary site for absorption.
     • Nephron Loop: Transports fluid through the medulla; reabsorbs salts and water.
     • Distal Convoluted Tubule (DCT): A short segment that is the specific target for several hormones.
     • Collecting Duct: Directs fluid toward the papilla and functions in water conservation.
• Associated Capillaries:
  • Peritubular Capillaries: Surround the tubules in the renal cortex to collect reabsorbed water and solutes.
  • Vasa Recta: Surround the nephron loops specifically in the renal medulla.
• Flow of Filtrate through the Nephron:
  • Afferent arteriole $\rightarrow$ Glomerular capsule $\rightarrow$ Proximal convoluted tubule $\rightarrow$ Nephron loop $\rightarrow$ Distal convoluted tubule $\rightarrow$ Collecting duct $\rightarrow$ Papillary duct $\rightarrow$ Minor calyx $\rightarrow$ Major calyx $\rightarrow$ Renal pelvis $\rightarrow$ Ureter $\rightarrow$ Urinary bladder $\rightarrow$ Urethra.

Physiology of Urine Formation I: Glomerular Filtration

• The Process: Blood plasma is converted to urine through Glomerular filtration, Tubular reabsorption and secretion, and Water conservation.
• Glomerular Filtration Function:
  • Water and small solutes are forced across the filtration barrier to create the starting fluid (filtrate).
  • Proteins are normally excluded from this process.
• Filtration Membrane:
  • Comprised of three layers: Capillary endothelium, Basement membrane, and Filtration slits (formed by podocyte feet).
• Selectivity:
  • Retained in Blood: Blood cells, large proteins.
  • Filtered into Nephron: Water, ions, glucose, amino acids, fatty acids, vitamins, urea, uric acid, and creatinine.
• Driving Force:
  • Filtration pressure results from Blood Hydrostatic Pressure (BHP).
  • BHP is high because the larger diameter of the afferent arteriole creates pressure against the smaller efferent arteriole.
• Clinical Markers of Damage:
  • Proteinuria (Albuminuria): Protein in the urine.
  • Hematuria: Blood in the urine.
  • Both can result from infection or trauma; temporary states often seen in distance runners and swimmers.

Regulation of Glomerular Filtration Rate (GFR)

• Definition: GFR is the volume of filtrate produced per minute by both kidneys. It must be regulated to maintain homeostasis.
  • High GFR: Fast flow leads to high urine output and dehydration.
  • Low GFR: Slow flow leads to excessive water absorption and potential azotemia.
• Method 1: Renal Autoregulation (Local Control):
  • Immediate control at the nephron via the Juxtaglomerular Apparatus.
  • Mesangial cells: Found within the glomerulus.
  • Juxtaglomerular (JG) cells: Cells that can constrict or relax the afferent arteriole and release Renin.
  • Macula densa cells: Sense ion and water levels; signal JG cells to adjust.
  • Negative Feedback Loop: High flow/GFR triggers the macula densa to signal JG cells to constrict the afferent arteriole.
• Method 2: Sympathetic Control:
  • Adrenal epinephrine and the sympathetic nervous system constrict afferent arterioles during strenuous exercise or circulatory shock.
  • This redirects blood from the kidneys to the heart, brain, and skeletal muscles, reducing GFR and urine output.
• Method 3: Hormonal Control (RAAS Mechanism):
  • Renin is secreted by JG cells if BP drops significantly.
  • Renin converts Angiotensinogen (liver protein) to Angiotensin I.
  • Angiotensin-Converting Enzyme (ACE) in the lungs and kidneys converts Angiotensin I into Angiotensin II.
  • Actions of Angiotensin II:
    • Potent vasoconstrictor.
    • Constricts the efferent arteriole to raise GFR.
    • Stimulates the Adrenal Cortex to secrete Aldosterone (increases $Na^+$ and $H_2O$ reabsorption in DCT/CD).
    • Stimulates the Posterior Pituitary to secrete Anti-diuretic Hormone (ADH) (increases water reabsorption in the CD).
    • Stimulates thirst in the brain.
• Effects of Hypertension:
  • High BP causes high pressure in the glomerulus, leading to ruptured capillaries, nephrosclerosis (scarring), atherosclerosis, and renal failure.

Physiology of Urine Formation II: Tubular Reabsorption and Secretion

• Proximal Convoluted Tubule (PCT):
  • Reabsorbs approximately $65\%$ of glomerular filtrate into peritubular capillaries.
  • Substances reabsorbed: Glucose, amino acids, Sodium ($Na^+$), and water (via aquaporins).
  • Substances secreted: Urea, ammonia, pollutants, penicillin, aspirin, $H^+$, and $HCO_3^-$ (for acid-base balance).
• Nephron Loop:
  • Reabsorbs another $25\%$ of the filtrate.
  • Moves salt from the filtrate into the tissue, making the renal medulla salty, which is essential for water conservation.
• Distal Convoluted Tubule (DCT):
  • Final site for determining urine composition; heavily influenced by hormones.
  • Aldosterone: Reabsorbs $Na^+$ into blood; water follows; urine output decreases.
  • Natriuretic peptides (ANP and BNP): Released by the heart in response to high BP; causes $Na^+$ to remain in urine; urine output increases.
  • Anti-diuretic hormone (ADH): Increases water retention; urine output decreases.
  • Parathyroid Hormone (PTH): Increases calcium reabsorption into the blood.
• Glucose Transport and Glycosuria:
  • Transporters in the tubule normally reabsorb all glucose.
  • If blood glucose is too high, transporters saturate (approx. $220\,mg/dL$), leading to glycosuria (glucose in urine).

Physiology of Urine Formation III: Water Conservation

• The Collecting Duct (CD):
  • Reabsorbs water and concentrates urine up to four times as it passes through the increasing salinity of the medulla.
• ADH and Aquaporins:
  • In Dehydration (Presence of ADH): More aquaporins are produced; water moves back into blood/tissues; concentrated (hypertonic) urine is produced in small volumes.
  • In Excess Water (Absence of ADH/Diuresis): No water is reabsorbed in the CD; large volumes of dilute (hypotonic) urine are produced.
• Diuretics:
  • Caffeine: Increases GFR by dilating the afferent arteriole.
  • Alcohol: Inhibits ADH secretion, reducing water retention.
  • Medical Use: Diuretics treat hypertension and heart failure by reducing fluid volume and blood pressure.

Urinalysis and Renal Function

• Physical Properties:
  • Appearance: Clear to deep amber. Yellow color is due to Urochrome pigment from hemoglobin breakdown.
  • Specific Gravity: Measure of density compared to water.
  • Osmolarity: Normal blood is $300\,mOsm/L$; dehydrated urine can reach $1,200\,mOsm/L$.
  • pH: Range from $4.5 - 8.2$; average is $6.0$ (mildly acidic).
• Chemical Composition: $95\%$ water, $5\%$ solutes.
  • Normal: Urea, $NaCl$, $KCl$, creatinine, uric acid, phosphates, sulfates.
  • Abnormal: Glucose, free hemoglobin, albumin, ketones, bile pigments.
• Urine Volume Terms:
  • Polyuria: Output > $2\,L/day$.
  • Oliguria: Output < $500\,mL/day$.
  • Anuria: Output $0 - 100\,mL/day$ (signals disease, shock, or blockage).

Case Studies and Scenarios

• Diabetes Mellitus:
  • Results in chronic polyuria, glycosuria, and increased appetite/thirst.
  • Joey's Diagnosis Scenario: Abnormal values of pH $3.5$, glucose $250\,mg/100\,mL$, ketones $10\,g/100\,mL$, and albumin $30\,mg/100\,mL$ indicate Diabetes Mellitus.
  • Reasoning: Ketonuria causes ketoacidosis (low pH); high blood glucose exceeds transport limits (glycosuria); albumin suggests pressure-induced kidney damage; high solutes increase specific gravity.
• Diabetes Insipidus:
  • Caused by ADH hyposecretion; results in low aquaporin count and severe polyuria without glycosuria.
• Jim Murray Scenario:
  • Diagnosis: Malignant hypertension and kidney failure.
  • Lab Values: BUN $200\,mg/dL$, Creatinine $22.4\,mg/dL$, Potassium $6.5\,mEq/L$, $CO_2\,12\,mEq/L$.
  • Expectation: CNS effects such as lethargy, forgetfulness, apathy, and drowsiness due to uremic toxins.

Urine Storage and Voiding (Micturition)

• Transportation and Storage:
  • Ureters are approximately $25\,cm$ long.
  • The Urinary Bladder contains the Detrusor muscle and Rugae (for expansion).
  • Trigone: Triangular area at the bladder base marked by the ureter and urethra openings.
  • Capacity: $500 - 800\,mL$.
• Urethral Sphincters:
  • Internal Urethral Sphincter: Smooth muscle; involuntary control.
  • External Urethral Sphincter: Skeletal muscle; voluntary control.
• Sexual Dimorphism:
  • Females: $3 - 4\,cm$ long.
  • Males: $18\,cm$ long with three regions: Prostatic ($2.5\,cm$), Membranous ($0.5\,cm$), and Spongy/Penile ($15\,cm$).
• Micturition Reflex:
  • 1. Involuntary Control: Bladder stretch activates sacral receptors, triggering parasympathetic contraction of the detrusor muscle.
  • 2. Voluntary Control: Signals sent to the thalamus and cerebral cortex allow for voluntary relaxation of the external sphincter.
  • Urinating Without Urge: The Valsalva maneuver can compress the bladder to excite stretch receptors early.

Questions & Discussion

• Question: What is the reason for the renal corpuscle?
• Answer: The renal corpuscle functions specifically as the filtration unit of the kidney. It uses the pressure differential created by the larger afferent and smaller efferent arterioles to force water and solutes out of the blood and into the tubule system to begin urine formation.
• Question: Explain the flow of the nephron.
• Answer: The flow begins as blood enters the renal corpuscle's glomerulus. Filtrate moves into the PCT, descends and ascends through the Nephron Loop, enters the DCT, and finally arrives at the Collecting Duct. From there, it drains into the papillary duct and the calyces for elimination.