The urinary system plays a crucial role in maintaining homeostasis by filtering blood and removing waste products. Urine formation and excretion are key processes in this system, involving complex mechanisms within the kidneys and urinary tract.

The kidneys filter blood through glomerular capillaries, reabsorb essential nutrients, and secrete additional waste products. This process is regulated by hormones and local factors, ultimately producing urine that helps maintain fluid balance and remove toxins from the body.

Urine formation and tubular secretion

Glomerular filtration

• Urine formation begins with glomerular filtration, where blood is filtered through the glomerular capillaries in the Bowman's capsule
• Creates an ultrafiltrate that enters the nephron tubule (contains water, glucose, amino acids, urea, and ions)
• High hydrostatic pressure in the glomerular capillaries drives the filtration process
• Filtration barrier prevents large molecules (proteins) and blood cells from entering the ultrafiltrate

Tubular reabsorption and secretion

• Tubular reabsorption is the second step, where the majority of the ultrafiltrate is reabsorbed back into the bloodstream as it passes through the nephron tubule
• Essential nutrients (glucose, amino acids) and water are reabsorbed, leaving behind waste products and excess substances
• Tubular secretion is the third step, where additional waste products and substances are actively secreted from the peritubular capillaries into the nephron tubule to be excreted in the urine
  • Substances secreted include hydrogen ions, potassium ions, ammonium ions, creatinine, and certain drugs (penicillin, morphine)
  • Allows for the removal of substances not initially filtered out of the blood during glomerular filtration, helping to maintain homeostasis
• Reabsorption and secretion processes are regulated by hormones (aldosterone, parathyroid hormone) and local factors (pH, concentration gradients)

Countercurrent multiplication system

Loop of Henle structure and function

• The loop of Henle is a U-shaped portion of the nephron that extends into the medulla of the kidney
• Consists of a descending limb permeable to water but not solutes and an ascending limb impermeable to water but permeable to solutes (sodium, potassium, chloride ions)
• Countercurrent flow of the filtrate (descending vs. ascending) and the recycling of solutes in the interstitium create a concentration gradient
• Concentration gradient becomes progressively greater towards the tip of the loop of Henle

Concentration gradient formation

• As the filtrate flows down the descending limb, water is reabsorbed out of the tubule and into the interstitium, making the filtrate more concentrated
• Concentrated filtrate flows up the ascending limb, and solutes are actively transported out of the tubule and into the interstitium, making the interstitium increasingly hyperosmotic
• Sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb actively pumps solutes into the interstitium
• Urea recycling from the collecting duct further contributes to the hyperosmotic medullary interstitium

Urine concentration

• The concentration gradient in the medulla allows for the reabsorption of water from the collecting duct, concentrating the urine before it is excreted
• Antidiuretic hormone (ADH) increases the permeability of the collecting duct to water, facilitating water reabsorption and urine concentration
• Concentrated urine helps to conserve water and maintain fluid balance in the body
• Disruption of the countercurrent multiplication system (loop diuretics, medullary damage) can lead to impaired urine concentrating ability

Factors influencing urine concentration

Hormonal factors

• Antidiuretic hormone (ADH), also known as vasopressin, is released by the posterior pituitary gland in response to dehydration or high blood osmolarity
  • Acts on the collecting ducts to increase water reabsorption and concentrate urine by inserting aquaporin-2 water channels
  • Deficiency (diabetes insipidus) or excess (SIADH) of ADH can lead to impaired urine concentration
• Aldosterone, released by the adrenal cortex, acts on the distal tubules and collecting ducts to increase sodium reabsorption and potassium secretion
  • Indirectly affects water reabsorption and urine concentration by altering the osmotic gradient
  • Excess aldosterone (primary hyperaldosteronism) can lead to hypertension and hypokalemia

Osmotic and volume factors

• Osmolarity of the blood and extracellular fluid affects the release of ADH, with high osmolarity stimulating ADH release and low osmolarity inhibiting it
  • Osmoreceptors in the hypothalamus detect changes in blood osmolarity and regulate ADH secretion
  • Increased blood osmolarity (dehydration, high salt intake) promotes ADH release and urine concentration
• Blood volume and pressure influence urine concentration and volume through the renin-angiotensin-aldosterone system (RAAS)
  • Decreased blood volume or pressure activates RAAS, leading to increased sodium and water reabsorption and reduced urine volume
  • Increased blood volume or pressure suppresses RAAS, leading to increased sodium and water excretion and increased urine volume
• Solute load, particularly the amount of urea and other waste products in the filtrate, can affect urine concentration by influencing the osmotic gradient in the medulla
  • High protein intake increases urea production and enhances urine concentrating ability
  • Renal disease (glomerulonephritis, renal failure) can impair urea excretion and urine concentration

Other factors

• Diuretics, such as caffeine and alcohol, can increase urine volume by inhibiting the reabsorption of water and solutes in the nephron tubules
  • Loop diuretics (furosemide) inhibit NKCC2 in the thick ascending limb, disrupting the countercurrent multiplication system
  • Thiazide diuretics (hydrochlorothiazide) inhibit sodium-chloride cotransporter (NCC) in the distal convoluted tubule
• Age-related changes in kidney function, such as reduced glomerular filtration rate and impaired concentrating ability, can affect urine volume and concentration
• Genetic factors, such as mutations in aquaporin-2 or ADH receptor genes, can cause inherited forms of nephrogenic diabetes insipidus and impair urine concentration

Micturition reflex and neural control

Micturition reflex pathway

• The micturition reflex, also known as the urination reflex, is a spinal reflex that controls the process of emptying the bladder when it becomes full
• Stretch receptors in the bladder wall detect the increase in bladder volume and send afferent signals via the pelvic nerves to the sacral region of the spinal cord (S2-S4)
• The spinal cord integrates the afferent signals and sends efferent signals via the pelvic nerves to the detrusor muscle (smooth muscle in the bladder wall) to contract and the internal urethral sphincter to relax, initiating urination
• The external urethral sphincter, which is under voluntary control, must also relax for urination to occur
  • Voluntary control allows for the conscious decision to delay or initiate urination
  • Innervated by the pudendal nerve (S2-S4)

Supraspinal control of micturition

• The pontine micturition center (PMC) in the brainstem plays a role in the supraspinal control of urination by coordinating the activity of the detrusor muscle and the external urethral sphincter
  • PMC receives input from the periaqueductal gray (PAG) and the hypothalamus regarding bladder fullness and the need to urinate
  • PMC sends descending signals to the sacral spinal cord to facilitate the micturition reflex
• The prefrontal cortex and other higher brain centers can exert voluntary control over the PMC and the external urethral sphincter, allowing for the conscious regulation of urination
  • These areas are involved in the decision-making process of when and where to urinate
  • Damage to the prefrontal cortex or its connections can lead to urinary incontinence or disinhibition

Disorders of micturition

• Urinary incontinence is the involuntary leakage of urine, which can result from various causes
  • Stress incontinence occurs due to increased abdominal pressure (coughing, sneezing, lifting) and weak pelvic floor muscles
  • Urge incontinence is associated with overactive bladder and involuntary detrusor contractions
  • Overflow incontinence results from a persistently full bladder due to impaired detrusor contractility or bladder outlet obstruction
• Urinary retention is the inability to completely empty the bladder, leading to a persistently high residual urine volume
  • Can be caused by bladder outlet obstruction (benign prostatic hyperplasia, urethral stricture), detrusor underactivity, or neurological disorders (spinal cord injury, multiple sclerosis)
• Overactive bladder syndrome is characterized by urinary urgency, frequency, and nocturia, with or without urge incontinence
  • Associated with involuntary detrusor contractions and increased bladder sensitivity
  • Treatment options include behavioral modifications, pelvic floor muscle training, anticholinergic medications, and neuromodulation