Anatomy & Physiology: The Urinary System

Overview of the Urinary System Structures

• The urinary system consists of two kidneys and the urinary tract.
• Kidneys filter blood, removing metabolic wastes while conserving fluid/electrolytes and regulating acid-base/blood pressure balance.
• The urinary tract is composed of a pair of ureters, the urinary bladder, and the urethra.
• Urine exits the kidneys through the ureters and enters the urinary bladder.
• Urine is stored in the urinary bladder on the floor of the pelvic cavity.
• Urine exits the urinary bladder through the urethra, allowing it to exit the body.

Overview of Kidney Function

• Kidneys regulate homeostatic processes, including filtering blood to remove metabolic wastes for elimination.
• They regulate fluid and electrolyte balance by managing osmolarity through water and electrolyte conservation or elimination
• Kidneys regulate acid-base balance and blood pH by adjusting hydrogen and bicarbonate ion levels.
• They influence blood pressure by managing blood volume and secreting enzymes affecting blood volume/peripheral resistance.
• The kidneys regulate red blood cell production (erythropoiesis) by secreting erythropoietin.
• Kidneys detoxify substances in blood, activate vitamin D, and synthesize new glucose (gluconeogenesis).

Internal Anatomy of the Kidneys

• On a frontal section of the kidney, three regions can be seen microscopically: the renal cortex, renal medulla, and renal pelvis.
• The urine-forming part of the kidney is made up of the renal cortex and renal medulla.
• The renal pelvis along with it's structures drain the urine formed in the cortex and medulla.
• The renal cortex is reddish-brown due to its rich blood supply.
• Of the kidney's blood vessels, 90-95% are in the renal cortex.
• Renal columns are extensions of the renal cortex that pass through the renal medulla toward the renal pelvis and house branches of the renal artery that travel to outer cortex.
• The cortex and medulla of each kidney contain over one million nephrons (filtering apparatus).
• Two main components make up nephrons: a globe-shaped renal corpuscle in the renal cortex and a long renal tubule primarily in the cortex while some tubules dip into the medulla.
• Renal medulla contains cone-shaped renal pyramids that are separated by renal columns.

Blood Supply of the Kidneys

• The kidney contains an unusual capillary bed system where arterioles both feed and drain capillaries.
• Normally venules perform the draining function typically for capillaries.
• Each interlobular artery leads to afferent arterioles, which feed a ball-shaped capillary bed (glomerulus).
• Part of renal corpuscle of nephron, glomerulus and its capillaries drain into the efferent arteriole.
• Efferent arteriole feeds into second capillary bed (peritubular capillaries).

Microanatomy of the Kidney: The Nephron and the Collecting System

• The nephron consists of two main divisions: the renal corpuscle, the renal tubule and their collective subdivisions.
• The renal corpuscle is responsible for filtering blood and is composed of two parts: the glomerulus and the glomerular capsule (Bowman's capsule).
• The glomerulus is a group of looping fenestrated capillaries that are extremely "leaky," or permeable.
• Glomerular capsule (Bowman's capsule) is a double-layered outer sheath of epithelial tissue, consisting of outer parietal and inner visceral layer.
• The visceral layer of the glomerular capsule is made of modified epithelial cells (podocytes) whose special extensions (foot processes, or pedicels) surround glomerular capillaries to form filtration slits.
• The capsular space is the hollow region between the parietal and visceral layers, continuous with the entrance of the renal tubule lumen.
• Podocytes and fenestrated glomerular capillaries form complex membrane that filters blood flowing through glomerulus.
• Filtered fluid (filtrate) exits glomerular capillaries into capsular space before entering lumen of renal tubule.
• Filtrate passes through three distinct regions of renal tubule: proximal tubule, nephron loop, and distal tubule.
• The renal tubule can be further modified here.
• The proximal tubule is the first and longest segment of the renal tubule, with straight and coiled sections made of simple cuboidal epithelial cells containing microvilli.
• The microvilli project into the tubule lumen to form a brush border, increasing the surface area of the region.
• Only part of the renal tubule to dip into the renal medulla is the nephron loop (loop of Henle), which consists of a descending and ascending limb.
• The descending limb is known as the thin descending limb because it is made of simple squamous epithelial cells and travels toward the renal medulla.
• Some nephrons have a thin ascending limb at the bend that consists of thin simple squamous epithelial cells, unlike the thicker simple cuboidal cells found in higher sections.
• The distal tubule features both straight and convoluted sections, which is last segment of renal tubule that filtrate passes through.
• The distal tubule, which is made of simple cuboidal epithelium without a brush border.
• Filtrate from distal tubules enters the cortical collecting duct (in renal cortex) to initiate the collecting system.
• The cortical collecting duct becomes the medullary collecting duct as it enters the renal medulla.
• Several medullary collecting ducts merge, forming a papillary duct; once filtrate enters it, it is known as urine, not filtrate.
• Urine exits the papillary duct at the papilla of renal pyramid and enters into the minor calyx.

Types of Nephrons

• Kidneys contain two structurally and functionally distinct nephrons – cortical and juxtamedullary.
• The distinction between these nephrons are there differences between their nephron loops and the organization of their peritubular capillaries.
• 80% of nephrons in kidneys are cortical nephrons, located in the renal cortex.
• Cortical nephron renal corpuscles are located in the outer renal cortex, with short nephron loops that barely enter the renal medulla, if at all.
• Blood is supplied to the loops of cortical nephrons via the peritubular capillaries indirectly through exchanging materials through interstitial fluid.
• Juxtamedullary nephrons are less common than cortical nephrons.
• Juxtamedullary nephron renal corpuscles are located near the boundary between the renal cortex and medulla and possess long nephron loops that travel deep within the renal medulla.
• Cortical portions of nephron surrounded by peritubular capillary branches; nephron loop surrounded by ladder-like network of capillaries (vasa recta) arising from efferent arteriole.
• The unique capillary structural arrangement enables juxtamedullary nephrons to modulate urine volume and concentration.

Nephrolithiasis

• Nephrolithiasis is the formation of renal calculi (kidney stones) that are crystalline structures most often made of calcium oxalate salts.
• When concentrations of ions (sodium, hydrogen, uric acid) are abnormally high in filtrate, crystals form; this is known as supersaturation.
• Crystals form in nephron loop, distal tubule, and collecting system, and may pass unnoticed in urine or adhere to tubular epithelium, forming seed crystals.
• Seed crystals lead to stones, which may remain in the collecting system or break off, lodging in calyces, renal pelvis, and ureter.
• Risk factors for kidney stones: dehydration, diet high in fat/animal protein/salt, and obesity.
• The most common symptom is severe pain (renal colic) radiating from lumbar region to pubic region, possibly with blood in urine, sweating, nausea, and vomiting.
• Diagnoses may be acquired via computed tomography (CT) or intravenous pyelogram (IVP) to visualize stone.

Glomerular Filtration

• Glomerular filtration is the initial process of nephrons which filters blood.
• Glomerular capillary membranes selectively filter blood based on size.
• Cells and large proteins are not filtered, and remain in blood circulation.
• Water, electrolytes (sodium/potassium ions), acids/bases (hydrogen/bicarbonate ions), organic molecules, and metabolic waste exit blood to enter capsular space as filtrate (tubular fluid).

Tubular Reabsorption

• As filtrate flows through tubules, it's modified via tubular reabsorption by removing substances.
• Reclaiming (reabsorbing) water, glucose, amino acids, and electrolytes from tubular fluid and returning them into circulating blood is priority.
• The nephron reabsorbs most filtered water and solutes from proximal tubule and nephron loop.
• Reabsorption becomes more precise in distal tubule/collecting duct; nephron adjusts reabsorption of different substances to maintain body homeostasis.

Tubular Secretion

• Substances are added into filtrate from peritubular capillaries for excretion from body via tubular secretion.
• This secretion may occur along entire tubule, with different substances secreted more in certain regions.
• It helps maintain electrolyte, acid-base homeostasis and removes toxins from blood that filtration did not filter.

The Filtration Membrane and the Filtrate

• Filtration membrane consists of three layers which collectively create a barrier from deep to superficial: fenestrated glomerular capillary endothelial cells, basal lamina, and podocytes.
• The deepest layer of this filtration barrier, fenestrated glomerular capillary endothelial cells, have fenestrations or “leaky" large pores between cells that prevent larger substances like blood cells, platelets, large proteins from exiting capillary blood flow.
• The basal lamina makes up the second layer and contains a thin layer of extracellular matrix gel.
• Collagen fibers form meshwork in the basal lamina that acts like a sieve, preventing substances larger than 8 nm in diameter from entering capsular space as well as blocking entry of most plasma proteins.
• The final barrier, the visceral layer, is made of glomerular capsule (podocytes) that must be passed before filtered substances can become filtrate in capsular space.
• As the membrane is the finest sieve of the three layers, it only allows substances smaller than 6–7 nm to pass into capsular space.
• Pore size affects the composition of fluids/solutes in capsular space as filtrate.
• Water and small dissolved solutes (glucose, amino acids, small proteins) pass through easily.
• Nitrogenous wastes, such as urea and ammonium ions (NH4+), creatinine, and uric acid, are readily filtered.

The Glomerular Filtration Rate (GFR)

• The glomerular filtration rate (GFR) is the amount of filtrate formed by both kidneys in one minute: 125 ml/min or all three liters of blood plasma filtered about 60 times a day.
• Fluid movement in a capillary bed driven by two forces that generate filtration pressures: Hydrostatic pressure and Colloid osmotic pressure.
• Hydrostatic pressure (blood pressure) is the force of fluid on capillary walls pushing water out of capillary into interstitial space.
• Colloid osmotic pressure (COP) is the pressure created by proteins (mostly albumin) in plasma where an osmotic gradient pulls water into capillaries by osmosis.
• Net filtration pressure (NFP) determining water's direction, comes from the interaction between hydrostatic and osmotic pressures.
• Water moves out of capillary when hydrostatic pressure exceeds COP and into capillary when COP exceeds hydrostatic pressure.

Glomerulonephritis

• Glomerulonephritis is a condition of glomerular damage, resulting in inflammation of capillaries and basement membrane.
• Inflammation increases blood flow, capillary permeability, and GHP, causing excessive leakiness in the filtration membrane as well as lead to blood cell and protein loss in urine.
• Nephrons are destroyed causing GFR decreases.
• Compensatory mechanisms increase GHP to maintain GFR, causing additional cell and protein loss.
• Eventually, GFR cannot be maintained, resulting in toxins accumulating in blood and possible renal failure.

Factors that Affect the Glomerular Filtration Rate

• Autoregulation consists of internal kidney mechanisms work to maintain GFR within normal range.
• The myogenic mechanism prevents increases in blood pressure and involves constriction of smooth muscle in blood vessel walls, preventing excessive blood flow.
• Increased systemic blood pressure stretches afferent arteriole, which increases GFR.
• That increase in GFR subsequently constricts afferent arteriole, reducing glomerular blood flow and returning GFR back to normal.
• Decreased systemic blood pressure stretches afferent arteriole less, which decreases GFR.
• That decrease in GFR subsequently relaxes smooth muscle, increasing blood flow through glomerulus, causing increase in GFR back toward normal range.
• Autoregulation works best for systemic blood pressure changes between 80 and 180 mmHg to restore GFR back to normal rapidly.
• Hormonal effects on GFR involve blood pressure regulation through angiotensin-II and natriuretic peptides.
• The renin-angiotensin-aldosterone system (RAAS) is a complex system that maintains systemic blood pressure (primarily) and GFR (secondarily), responding to the following.
  • sympathetic nervous system stimulation
  • low glomerular hydrostatic pressure
  • macula densa stimulation
• Reduced blood pressure decreases GFR which triggers JG cells release renin to bloodstream.
• Subsequently, renin converts angiotensinogen to angiotensin-I, then to more active angiotensin-II by angiotensin-converting enzyme (ACE), which is produced by lung endothelial cells.
• Angiotensin-II promotes vasoconstriction of efferent arterioles/systemic blood vessels and reabsorption of sodium/chloride ions/water from proximal tubule.
• Also, aldosterone release to promote sodium/water reabsorption and increased thirst lead to increased systemic blood pressure and GFR.
• Atrial natriuretic peptide (ANP) is a hormone released by heart cells in atria in response to fluid volume increase and lower blood volume/pressure to reduce workload of heart.
• ANP increases GFR via afferent arteriole dilation and efferent arteriole constriction to increase glomerular hydrostatic pressure.
• Blood volume reduction from kidneys favoring fluid loss through high GFR results in lowered systemic blood pressure.
• Sympathetic division of nervous system primarily controls the neural regulation of GFR through using norepinephrine to control systemic blood pressure.
• Increased sympathetic activity constricts afferent arterioles, increasing systemic blood pressure, and level of stimulation affects GFR.
• Sympathetic stimulation can also cause JG cells to release renin, raising systemic blood pressure/GFR through angiotensin-II formation.

Renal Failure

• If the kidneys are unable to carry out their vital functions due to decreased GFR, this is known as renal failure.
• Renal failure that resolves with treatment may be a short-term condition (acute renal failure or acute kidney injury).
• A chronic condition develops if there is a renal failure after three or more months of decreased GFR, which is common with long-standing diabetes mellitus and hypertension.
• The condition known as uremia develops when GFR less than 50% of normal.
• Electrolyte imbalances and buildup of waste products and fluid subsequently leads to coma, seizures, and death, if untreated.
• Dialysis, which is treatment, alleviates the signs and symptoms of uremia.
• Hemodialysis involves filter-passing blood that reduces metabolic waste and fluid levels, while also normalizing electrolyte and acid-base balances.
• Peritoneal dialysis involves dialysis fluid placed in peritoneal cavity to remove metabolic waste and fluid while restoring electrolyte and acid-base balance.

The RAAS and Hypertension

• To reduce blood pressure, three classes of drugs act on RAAS
  • ACE inhibitors block ACE from converting angiotensin I to II
  • angiotensin-receptor blockers prevent vasoconstriction & water/sodium reabsorption from blood vessels/proximal tubule cells.
  • aldosterone antagonists block aldosterone, decrease sodium/water reabsorption, and cause diuretic effect in distal tubule.
• Decreased GFR may result from in patients with pre-existing renal disease because of the usage of drugs, therefore it must be monitored.

Principles of Tubular Reabsorption and Secretion

• Substances involved in tubular reabsorption pass from filtrate in tubule across tubule cells into interstitial fluid then across endothelial cells of peritubular capillaries.
• Substances involved in tubular secretion moves in the opposite direction.

Glycosuria

• It is especially important for substances such as glucose to have a transport maximum.
• Transport maximum (TM) of glucose in filtrate is commonly seen in diabetes mellitus where there are defects in production of/response to insulin.
• High levels of blood glucose (hyperglycemia) cause elevated glucose levels in the filtrate, causing any glucose remaining in urine to reach TM before all glucose is reabsorbed.

Reabsorption and Secretion in the Proximal Tubule

• The primary function of the proximal tubule involves the reabsorption of filtrate to the blood.
• Ions, such as sodium, potassium, chloride, sulfate, and phosphate, are reabsorbed for electrolyte homeostasis.
• Nutrients, including glucose, amino acids, water-soluble vitamins, and lactic acid, are reabsorbed almost entirely.
• Bicarbonate ions, essential to acid-base homeostasis, are reabsorbed.
• About 65% of filtered water is vital to maintenance of fluid homeostasis.
• Sodium ion reabsorption is extremely important to many other substance that reabsorb to proximal tubule.
• Two transcellular mechanisms: facilitated diffusion via ion leak channels and active transport via three carrier proteins.
• Carrier proteins are sodium ion-specific and enable diffusion from filtrate into cells while Na+ symporters transport sodium ions with other substances into the tubule cell from filtrate Na+/H+ antiporters brings sodium ions into cell while secreting hydrogen ions into filtrate.
• Na+/K+ pumps cause a gradient via moving sodium ions into interstitial fluid from the basolateral membrane.
• Because of Na+/H+ antiporter activity from a reversible chemical reaction, bicarbonate ion reabsorption occurs.
• Hydrogen ions are secreted and combined with bicarbonate ions in filtrate, forming carbonic acid (H₂CO₃).
• Carbonic anhydrase (enzyme) on tubule cell membrane converts carbonic acid into CO2 and H2O.
• Cells of proximal tubule maintain pH in blood within 7.35–7.45 through reabsorbing 90% of bicarbonate ions.
• Channels (aquaporins) in apical and basolateral cell membranes reabsorb water and also increase water reabsorption.
• Diffusion into tubule cells is favored as concentration of magnesium. calcium, and potassium ions increase in filtrate, since water is reabsorbed.
• Hydrogen ions, drugs, and nitrogenous wastes can be secreted in proximal tubule.
• Most uric acid filtered may be reabsorbed and then secondarily secreted in the second half of tubule.
• Ammonium ions (NH4+), creatinine, and small urea may also be secreted.
• Amounts of drugs lost via secretion (3–5 times per day) will need to be replaced in order to maintain relatively consistent blood levels.

Reabsorption in the Nephron Loop

• 60-70% of water and electrolytes and most organic solutes been returned to blood, once filtrate enters nephron loop
• The nephron loop reabsorbs about 20% of water and 25% of sodium/chloride ions.
• Water reabsorption is proportional to solute reabsorption where filtrate and interstitial is about 300 mOsm.
• Filtrate increases its osmolarity from changes that occur in descending and ascending limbs.
• Thin descending limbs feature high water permeability, but limited permeability to solutes.
• Water passes into cells of limb from osmosis and increases filtrate osmolarity after following descending limb.
• Thick ascending limb cell are water impermeable and drives solutes into cells via Na+/K+/2Cl- symporters.
• One sodium, potassium, and two chloride ions enters tubule cell via gradient; Na+/K+ pump drives gradient on gradient to basolateral membrane.
• Na+/K+ pumps drive potassium ions back into tubule cell, causing reabsorption of potassium ions to be limited.
• Solutes are lost and concentration lessen as filtrate passes limb into ascending limb.

Reabsorption and Secretion-Distal Tubule and Collecting System

• 85% of water, 90% of sodium ions have been reabsorbed by the time filtrate has reached distal tubule.
• The rate of filtrate flow in distal tubule is slower (20 ml/min) compared to proximal tubule (120 ml/min).
• Cortical collecting duct and ascending nephron limb share structural/functional similarities; discussed as a single topic.
• Medullary collecting system will structural and functionally discussed at a later time.
• A hormone fine-tune water, electrolyte, and acid-base balance via receptors on principal cells of late distal tubule & collecting duct.
• “Facultative" water reabsorption depends on body needs.
• Aldosterone (steroid hormone) released by adrenal cortex increases permeability to/number of sodium ions.
• Na+/K+ pump increases, sodium ions are reabsorbed, and potassium ions are secreted/antidiuretic hormones present or not.
• Antidiuretic hormone (ADH) from the hypothalamus and posterior pituitary causes water reabsorption to reduce urine.
• Aquaporins into apical membranes causes aforementioned effects (more permeable).
• Larger water volume is lost into urine and vice versa, which depends on the water level present in urine.
• Hormone release, atrial natriuretic peptide (ANP) stimulates urinary excretion from sodium ions (natriuresis).
• Less sodium ions (and water) resulting, increasing in water/sodium excretion given both aldosterone and ADH inhibit their former properties.
• Last chance for electrolyte and acid-base balance regulation is the medullary collecting system.
• Impermeable to water without the assistance of ADH which are needed for water retention.
• Allows passive reabsorption through urea (high permeable rate and volume).
• Retains reabsorptions levels to reabsorb to pre-existing ions (sodium, chloride, and bicarbonate from filtrate).

How Tubular Reabsorption and Secretion Maintain Acid-Base Balance

• Proximal tubule cells secrete hydrogen ions to reabsorb bicarbonate ions, while distal tubule cells actively secrete hydrogen ions.
• When blood pH decreases (becomes too acidic):
• Enzymes in tubule cells remove amino group (NH2) from amino acid glutamine.
• Ammonia (NH3) and bicarbonate molecules generate; ammonia is secreted into filtrate and bicarbonate is reabsorbed into blood.
• When blood pH decreases (continued):
• Ammonia acts as a buffer, binding to hydrogen ions and forming ammonium ions (NH4+) in filtrate.
• The combination of ammonia buffering and bicarbonate reabsorption brings the pH back up to normal.
• If blood pH increases (becomes too alkaline), tubule cells will reabsorb less bicarbonate ions from filtrate; lowers blood pH as ions are excreted in urine.

Osmolarity of Filtrate

• 85% is obligatory, what remains after this is used and adjusted according to the needs of the body.
• This adjustment from the remaining 15% determines the final urine concentration and volume.

Production of Dilute Urine

• Kidneys produce dilute urine when solute concentration of extracellular fluid is too low.
• Turning off of ADH hormone release turns off facultative reabsorption which now makes the distal tubule and collecting duct become impermeable to water.
• Osmolarity can fall to 50 mOsm from elimination of excess ECF water.

Countercurrent Mechanism and Production of Concentrated Urine

• By producing urine using two mechanisms kidneys conserve water effectively:
• Turning on releases of ADH due to facultative reabsorption.
• Water happens through osmosis, meaning a present concentration gradient is needed.

Urine Composition and Urinalysis

• Urine normally contains:
  • Water
  • Sodium
  • Potassium
  • Chloride
  • Hydrogen ion
  • Phosphates
• Sulfates
• Metabolic wastes (urea, creatinine, ammonia, uric acid)
• Small amounts of bicarbonate, calcium, and magnesium
• Urinalysis analyzes urine to detect a disease:
  • Color
• Yellow pigment called urochrome
• Darker urine means more concentrated
• Lighter urine means less concentrated
• Urine should be translucent & cloudy urine indicates an infection

Urine Composition and Urinalysis (continued)

• Freshly voided urine should have a mild odor. Strong odors may be caused by diseases, infections, or ingestion.
• The normal pH is slightly acidic (6.0)
• Specific gravity compares the amount of solute in the solution to deionized water. (Should be greater than 1.0)
  • Normal ranges between 1.001 (very dilute) to 1.035 (very concentrated).

SIADH

• Characterized by excess ADH secretion (Syndrome of inappropriate ADH secretion).
• Multiple causes, most likely ADH-secreting tumors.
• Results in excess fluid retention leading to decreased plasma osmolarity while increased urine osmolarity.

Anatomy of the Urinary Tract

• Urinary tract consists of two ureters, the bladder, and urethra
• Adult uterus consists of 25-30 cm length and diameter of 3-4 nm, begins levels of 2nd lumbar nerves, travels behind and empties into bladder, walls are comprised of three layers Adventitia is most superficial and supports uterus Muscularis is the middle level, composed of muscle that contracts that causes peristalsis for bladder Mucosa is deepest and houses mucous for contracting/expanding.
• The urinary bladder is hollow and held by parietal peritoneum. Collapses when emptied but has pear-shape with holding levels of 700-800ml. Trigone is a triangular region on floor; openings of ureters present at corner in back. Adentitia- most superficial, folds of parietal peritoneum over bladder's surface. Muscle (detrusor)- middle with squeezing abilities. Internal urethral sphincter at opening. Mucosa: Innermost layer made of membrane while provides protection.
• Urethra is last line, while walls and levels are similar to ureters. Unlike others:
• Opening surrounded by sphincter and external urethral with muscles needed for voluntary control. Male and female diff. Females has 4cm length, external opening, serves exit line Males has 20cm parts: glands (prostatic), membranes(muscle), corpus(spongisoum) Micturition- voiding & contraction from bladder to body Micturition reflex - arc from nervous system needed to stretch wall. Stretch receptors send signal from spinal cord, and fibers contract for micturition. Voluntary contraction (time & training) from micturition center to muscle