Urinary System Notes

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The Urinary System:
Urinary System Organs
* Kidneys are major excretory organs
* Urinary bladder is the temporary storage reservoir for urine
* Ureters transport urine from the kidneys to the bladder
* Urethra transports urine out of the body
Kidney Functions
* Removal of toxins, metabolic wastes, and excess ions from the blood
* Regulation of blood volume, chemical composition, and pH
Kidney Functions
* Gluconeogenesis during prolonged fasting
* Endocrine functions
* Renin: regulation of blood pressure and kidney function
* Erythropoietin: regulation of RBC production
* Activation of vitamin D Kidney Anatomy
* Retroperitoneal, in the superior lumbar region
* Right kidney is lower than the left
* Convex lateral surface, concave medial surface
* Renal hilum leads to the renal sinus
* Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilum
Kidney Anatomy
* Layers of supportive tissue
* Renal fascia
* The anchoring outer layer of dense fibrous connective tissue
* Perirenal fat capsule
* A fatty cushion
* Fibrous capsule
* Prevents spread of infection to kidney
Internal Anatomy
* Renal cortex
* A granular superficial region
* Renal medulla
* The cone-shaped medullary (renal) pyramids separated by renal columns
* Lobe
* A medullary pyramid and its surrounding cortical tissue
Internal Anatomy
* Papilla
* Tip of pyramid; releases urine into minor calyx
* Renal pelvis
* The funnel-shaped tube within the renal sinus
Internal Anatomy
* Major calyces
* The branching channels of the renal pelvis that
* Collect urine from minor calyces
* Empty urine into the pelvis
* Urine flows from the pelvis to ureter
Blood and Nerve Supply
* Renal arteries deliver ~ 1/4 (1200 ml) of cardiac output to the kidneys each minute
* Arterial flow into and venous flow out of the kidneys follow similar paths
* Nerve supply is via sympathetic fibers from the renal plexus
Nephrons
* Structural and functional units that form urine
* ~1 million per kidney
* Two main parts
* Glomerulus: a tuft of capillaries
* Renal tubule: begins as cup-shaped glomerular (Bowman’s) capsule surrounding the glomerulus
Nephrons
* Renal corpuscle
* Glomerulus + its glomerular capsule
* Fenestrated glomerular endothelium
* Allows filtrate to pass from plasma into the glomerular capsule
Renal Tubule
* Glomerular capsule
* Parietal layer: simple squamous epithelium
* Visceral layer: branching epithelial podocytes
* Extensions terminate in foot processes that cling to basement membrane
* Filtration slits allow filtrate to pass into the capsular space
Renal Tubule
* Proximal convoluted tubule (PCT)
* Cuboidal cells with dense microvilli and large mitochondria
* Functions in reabsorption and secretion
* Confined to the cortex
Renal Tubule
* Loop of Henle with descending and ascending limbs
* Thin segment usually in descending limb
* Simple squamous epithelium
* Freely permeable to water
* Thick segment of ascending limb
* Cuboidal to columnar cells
Renal Tubule
* Distal convoluted tubule (DCT)
* Cuboidal cells with very few microvilli
* Function more in secretion than reabsorption
* Confined to the cortex
Collecting Ducts
* Receive filtrate from many nephrons
* Fuse together to deliver urine through papillae into minor calyces
Collecting Ducts
* Cell types
* Intercalated cells
* Cuboidal cells with microvilli
* Function in maintaining the acid-base balance of the body
Collecting Ducts
* Principal cells
* Cuboidal cells without microvilli
* Help maintain the body’s water and salt balance
Nephrons
* Cortical nephrons—85% of nephrons; almost entirely in the cortex
* Juxtamedullary nephrons
* Long loops of Henle deeply invade the medulla
* Extensive thin segments
* Important in the production of concentrated urine
Nephron Capillary Beds
* Glomerulus
* Afferent arteriole ® glomerulus ® efferent arteriole
* Specialized for filtration
* Blood pressure is high because
* Afferent arterioles are smaller in diameter than efferent arterioles
* Arterioles are high-resistance vessels
Nephron Capillary Beds
* Peritubular capillaries
* Low-pressure, porous capillaries adapted for absorption
* Arise from efferent arterioles
* Cling to adjacent renal tubules in cortex
* Empty into venules
Nephron Capillary Beds
* Vasa recta
* Long vessels parallel to long loops of Henle
* Arise from efferent arterioles of juxtamedullary nephrons
* Function information of concentrated urine
Vascular Resistance in Microcirculation
* High resistance in afferent and efferent arterioles
* Causes blood pressure to decline from ~95 mm Hg to ~8 mm Hg in kidneys
Vascular Resistance in Microcirculation
* Resistance in afferent arterioles
* Protects glomeruli from fluctuations in systemic blood pressure
* Resistance in efferent arterioles
* Reinforces high glomerular pressure
* Reduces hydrostatic pressure in peritubular capillaries
Juxtaglomerular Apparatus (JGA)
* One per nephron
* Important in regulation of filtrate formation and blood pressure
* Involves modified portions of the
* Distal portion of the ascending limb of the loop of Henle
* Afferent (sometimes efferent) arteriole
Juxtaglomerular Apparatus (JGA)
* Granular cells (juxtaglomerular, or JG cells)
* Enlarged, smooth muscle cells of arteriole
* Secretory granules contain renin
* Act as mechanoreceptors that sense blood pressure
Juxtaglomerular Apparatus (JGA)
* Macula densa
* Tall, closely packed cells of the ascending limb
* Act as chemoreceptors that sense NaCl content of filtrate
* Extraglomerular mesangial cells
* Interconnected with gap junctions
* May pass signals between macula densa and granular cells
Filtration Membrane
* Porous membrane between the blood and the capsular space
* Consists of
* Fenestrated endothelium of the glomerular capillaries
* Visceral membrane of the glomerular capsule (podocytes with foot processes and filtration slits)
* Gel-like basement membrane (fused basal laminae of the two other layers)
Filtration Membrane
* Allows passage of water and solutes smaller than most plasma proteins
* Fenestrations prevent filtration of blood cells
* Negatively charged basement membrane repels large anions such as plasma proteins
* Slit diaphragms also help to repel macromolecules
Filtration Membrane
* Glomerular mesangial cells
* Engulf and degrade macromolecules
* Can contract to change the total surface area available for filtration
Kidney Physiology: Mechanisms of Urine Formation
* The kidneys filter the body’s entire plasma volume 60 times each day
* Filtrate
* Blood plasma minus proteins
* Urine
* 5 nm are not filtered (e.g., plasma proteins) and function to maintain colloid osmotic pressure of the blood
Net Filtration Pressure (NFP)
* The pressure responsible for filtrate formation (10 mm Hg)
Net Filtration Pressure (NFP)
* Determined by
* Glomerular hydrostatic pressure (HPg) the chief force
* Two opposing forces:
* Colloid osmotic pressure of glomerular blood (OPg)
* Capsular hydrostatic pressure (HPc)
NFP = HPg – (OPg + HPc)
Glomerular Filtration Rate (GFR)
* Volume of filtrate formed per minute by the kidneys (120–125 ml/min)
* Governed by (and directly proportional to)
* Total surface area available for filtration
* Filtration membrane permeability
* NFP
Regulation of Glomerular Filtration
* GFR is tightly controlled by two types of mechanisms
* Intrinsic controls (renal autoregulation)
* Act locally within the kidney
* Extrinsic controls
* Nervous and endocrine mechanisms that maintain blood pressure, but affect kidney function
Intrinsic Controls
* Maintains a nearly constant GFR when MAP is in the range of 80–180 mm Hg
* Two types of renal autoregulation
* Myogenic mechanism (Chapter 19)
* Tubuloglomerular feedback mechanism, which senses changes in the juxtaglomerular apparatus
Intrinsic Controls: Myogenic Mechanism
* ­ BP ® constriction of afferent arterioles
* Helps maintain normal GFR
* Protects glomeruli from damaging high BP
* ¯ BP ® dilation of afferent arterioles
* Helps maintain normal GFR
Intrinsic Controls: Tubuloglomerular Feedback Mechanism
* Flow-dependent mechanism directed by the macula densa cells
* If GFR increases, filtrate flow rate increases in the tubule
* Filtrate NaCl concentration will be high because of insufficient time for reabsorption
Intrinsic Controls: Tubuloglomerular Feedback Mechanism
* Macula densa cells of the JGA respond to ­NaCl by releasing a vasoconstricting chemical that acts on the afferent arteriole ® ¯ GFR
* The opposite occurs if GFR decreases.
Extrinsic Controls: Sympathetic Nervous System
* Under normal conditions at rest
* Renal blood vessels are dilated
* Renal autoregulation mechanisms prevail
Extrinsic Controls: Sympathetic Nervous System
* Under extreme stress
* Norepinephrine is released by the sympathetic nervous system
* Epinephrine is released by the adrenal medulla
* Both cause constriction of afferent arterioles, inhibiting filtration and triggering the release of renin
Extrinsic Controls: Renin-Angiotensin Mechanism
* Triggered when the granular cells of the JGA release renin angiotensinogen (a plasma globulin) resin ® angiotensin I angiotensin converting enzyme (ACE) ® angiotensin II
Effects of Angiotensin II
* Constricts arteriolar smooth muscle, causing MAP to rise
* Stimulates the reabsorption of Na+
* Acts directly on the renal tubules
* Triggers adrenal cortex to release aldosterone
* Stimulates the hypothalamus to release ADH and activates the thirst center
Effects of Angiotensin II
* Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption
* Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration
Extrinsic Controls: Renin-Angiotensin Mechanism
* Triggers for renin release by granular cells
* Reduced stretch of granular cells (MAP below 80 mm Hg)
* Stimulation of the granular cells by activated macula densa cells
* Direct stimulation of granular cells via b1-adrenergic receptors by renal nerves
Other Factors Affecting GRF
* Prostaglandin E2
* Vasodilator that counteracts vasoconstriction by norepinephrine and angiotensin II
* Prevents renal damage when peripheral resistance is increased
Other Factors Affecting GRF
* Intrarenal angiotensin II
* Reinforces the effects of hormonal angiotensin II
* Adenosine
* A vasoconstrictor of renal vasculature

Tubular Reabsorption
* A selective transepithelial process
* All organic nutrients are reabsorbed
* Water and ion reabsorption are hormonally regulated
* Includes active and passive process
* Two routes
* Transcellular
* Paracellular
Tubular Reabsorption
* Transcellular route
* Luminal membranes of tubule cells
* Cytosol of tubule cells
* Basolateral membranes of tubule cells
* Endothelium of peritubular capillaries
Tubular Reabsorption
* Paracellular route
* Between cells
* Limited to water movement and reabsorption of Ca2+, Mg2+, K+, and some Na+ in the PCT where tight junctions are leaky
Sodium Reabsorption
* Na+ (most abundant cation in filtrate)
* Primary active transport out of the tubule cell by Na+-K+ ATPase in the basolateral membrane
* Na+ passes in through the luminal membrane by secondary active transport or facilitated diffusion mechanisms
Sodium Reabsorption
* Low hydrostatic pressure and high osmotic pressure in the peritubular capillaries
* Promotes bulk flow of water and solutes (including Na+)
Reabsorption of Nutrients, Water, and Ions
* Na+ reabsorption provides the energy and the means for reabsorbing most other substances
* Organic nutrients are reabsorbed by secondary active transport
* Transport maximum (Tm) reflects the number of carriers in the renal tubules available
* When the carriers are saturated, excess of that substance is excreted
Reabsorption of Nutrients, Water, and Ions
* Water is reabsorbed by osmosis (obligatory water reabsorption), aided by water-filled pores called aquaporins
* Cations and fat-soluble substances follow by diffusion
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
* PCT
* Site of most reabsorption
* 65% of Na+ and water
* All nutrients
* Ions
* Small proteins
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
* Loop of Henle
* Descending limb: H2O
* Ascending limb: Na+, K+, Cl-
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
* DCT and collecting duct
* Reabsorption is hormonally regulated
* Ca2+ (PTH)
* Water (ADH)
* Na+ (aldosterone and ANP)
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
* Mechanism of aldosterone
* Targets collecting ducts (principal cells) and distal DCT
* Promotes synthesis of luminal Na+ and K+ channels
* Promotes synthesis of basolateral Na+-K+ ATPases
Tubular Secretion
* Reabsorption in reverse
* K+, H+, NH4+, creatinine, and organic acids move from peritubular capillaries or tubule cells into filtrate
* Disposes of substances that are bound to plasma proteins
Tubular Secretion
* Eliminates undesirable substances that have been passively reabsorbed (e.g., urea and uric acid)
* Rids the body of excess K+
* Controls blood pH by altering amounts of H+ or HCO3– in urine
Regulation of Urine Concentration and Volume
* Osmolality
* Number of solute particles in 1 kg of H2O
* Reflects ability to cause osmosis
Regulation of Urine Concentration and Volume
* Osmolality of body fluids
* Expressed in milliosmols (mOsm)
* The kidneys maintain osmolality of plasma at ~300 mOsm, using countercurrent mechanisms
Countercurrent Mechanism
* Occurs when fluid flows in opposite directions in two adjacent segments of the same tube
* Filtrate flow in the loop of Henle (countercurrent multiplier)
* Blood flow in the vasa recta (countercurrent exchanger)
Countercurrent Mechanism
* Role of countercurrent mechanisms
* Establish and maintain an osmotic gradient (300 mOsm to 1200 mOsm) from renal cortex through the medulla
* Allow the kidneys to vary urine concentration
Countercurrent Multiplier: Loop of Henle
* Descending limb
* Freely permeable to H2O, which passes out of the filtrate into the hyperosmotic medullary interstitial fluid
* Filtrate osmolality increases to ~1200 mOsm
Countercurrent Multiplier: Loop of Henle
* Ascending limb
* Impermeable to H2O
* Selectively permeable to solutes
* Na+ and Cl– are passively reabsorbed in the thin segment, actively reabsorbed in the thick segment
* Filtrate osmolality decreases to 100 mOsm
Urea Recycling
* Urea moves between the collecting ducts and the loop of Henle
* Secreted into filtrate by facilitated diffusion in the ascending thin segment
* Reabsorbed by facilitated diffusion in the collecting ducts deep in the medulla
* Contributes to the high osmolality in the medulla
Countercurrent Exchanger: Vasa Recta
* The vasa recta
* Maintain the osmotic gradient
* Deliver blood to the medullary tissues
* Protect the medullary osmotic gradient by preventing rapid removal of salt, and by removing reabsorbed H2O
Formation of Dilute Urine
* Filtrate is diluted in the ascending loop of Henle
* In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine
* Na+ and other ions may be selectively removed in the DCT and collecting duct, decreasing osmolality to as low as 50 mOsm
Formation of Concentrated Urine
* Depends on the medullary osmotic gradient and ADH
* ADH triggers reabsorption of H2O in the collecting ducts
* Facultative water reabsorption occurs in the presence of ADH so that 99% of H2O in filtrate is reabsorbed
Diuretics
* Chemicals that enhance the urinary output
* Osmotic diuretics: substances not reabsorbed, (e.g., high glucose in a diabetic patient)
* ADH inhibitors such as alcohol
* Substances that inhibit Na+ reabsorption and obligatory H2O reabsorption such as caffeine and many drugs
Renal Clearance
* Volume of plasma cleared of a particular substance in a given time
* Renal clearance tests are used to
* Determine GFR
* Detect glomerular damage
* Follow the progress of renal disease
Renal Clearance
RC = UV/P
RC = renal clearance rate (ml/min)
U = concentration (mg/ml) of the substance in urine
V = flow rate of urine formation (ml/min)
P = concentration of the same substance in plasma
Renal Clearance
* For any substance freely filtered and neither reabsorbed nor secreted by the kidneys (e.g., insulin),
RC = GFR = 125 ml/min
* If RC < 125 ml/min, the substance is reabsorbed
* If RC = 0, the substance is completely reabsorbed
* If RC > 125 ml/min, the substance is secreted (most drug metabolites)
Physical Characteristics of Urine
* Color and transparency
* Clear, pale to deep yellow (due to urochrome)
* Drugs, vitamin supplements, and diet can alter the color
* Cloudy urine may indicate a urinary tract infection
Physical Characteristics of Urine
* Odor
* Slightly aromatic when fresh
* Develops ammonia odor upon standing
* May be altered by some drugs and vegetables
Physical Characteristics of Urine
* pH
* Slightly acidic (~pH 6, with a range of 4.5 to 8.0)
* Diet, prolonged vomiting, or urinary tract infections may alter pH
* Specific gravity
* 1.001 to 1.035, dependent on solute concentration
Chemical Composition of Urine
* 95% water and 5% solutes
* Nitrogenous wastes: urea, uric acid, and creatinine
* Other normal solutes
* Na+, K+, PO43–, and SO42–,
* Ca2+, Mg2+ and HCO3–
* Abnormally high concentrations of any constituent may indicate pathology
Ureters
* Convey urine from kidneys to bladder
* Retroperitoneal
* Enter the base of the bladder through the posterior wall
* As bladder pressure increases, distal ends of the ureters close, preventing backflow of urine
Ureters
* Three layers of wall of ureter
* Lining of transitional epithelium
* Smooth muscle muscularis
* Contracts in response to stretch
* Outer adventitia of fibrous connective tissue
Renal Calculi
* Kidney stones form in renal pelvis
* Crystallized calcium, magnesium, or uric acid salts
* Larger stones block ureter, cause pressure and pain in kidneys
* May be due to chronic bacterial infection, urine retention, ­Ca2+ in blood, ­pH of urine
Urinary Bladder
* Muscular sac for temporary storage of urine
* Retroperitoneal, on pelvic floor posterior to pubic symphysis
* Males—prostate gland surrounds the neck inferiorly
* Females—anterior to the vagina and uterus
Urinary Bladder
* Trigone
* Smooth triangular area outlined by the openings for the ureters and the urethra
* Infections tend to persist in this region
Urinary Bladder
* Layers of the bladder wall
* Transitional epithelial mucosa
* Thick detrusor muscle (three layers of smooth muscle)
* Fibrous adventitia (peritoneum on superior surface only)
Urinary Bladder
* Collapses when empty; rugae appear
* Expands and rises superiorly during filling without significant rise in internal pressure
Urethra
* Muscular tube
* Lining epithelium
* Mostly pseudostratified columnar epithelium, except
* Transitional epithelium near bladder
* Stratified squamous epithelium near external urethral orifice
Urethra
* Sphincters
* Internal urethral sphincter
* Involuntary (smooth muscle) at bladder-urethra junction
* Contracts to open
* External urethral sphincter
* Voluntary (skeletal) muscle surrounding the urethra as it passes through the pelvic floor
Urethra
* Female urethra (3–4 cm):
* Tightly bound to the anterior vaginal wall
* External urethral orifice is anterior to the vaginal opening, posterior to the clitoris
Urethra
* Male urethra
* Carries semen and urine
* Three named regions
* Prostatic urethra (2.5 cm)—within prostate gland
* Membranous urethra (2 cm)—passes through the urogenital diaphragm
* Spongy urethra (15 cm)—passes through the penis and opens via the external urethral orifice
Micturition
* Urination or voiding
* Three simultaneous events
* Contraction of detrusor muscle by ANS
* Opening of internal urethral sphincter by ANS
* Opening of external urethral sphincter by somatic nervous system
Micturition
* Reflexive urination (urination in infants)
* Distension of bladder activates stretch receptors
* Excitation of parasympathetic neurons in reflex center in sacral region of spinal cord
* Contraction of the detrusor muscle
* Contraction (opening) of internal sphincter
* Inhibition of somatic pathways to external sphincter, allowing its relaxation (opening)
Micturition
* Pontine control centers mature between ages 2 and 3
* Pontine storage center inhibits micturition:
* Inhibits parasympathetic pathways
* Excites sympathetic and somatic efferent pathways
* Pontine micturition center promotes micturition:
* Excites parasympathetic pathways
* Inhibits sympathetic and somatic efferent pathways
Developmental Aspects
* Three sets of embryonic kidneys forming succession
* Pronephros degenerates but pronephric duct persists
* Mesonephros claims this duct and it becomes the mesonephric duct
* Metanephros develops by the fifth week, develops into adult kidneys and ascends
Developmental Aspects
* Metanephros develops as ureteric buds that induce mesoderm of urogenital ridge to form nephrons
* Distal ends of ureteric buds form renal pelves, calyces, and collecting ducts
* Proximal ends become ureters
* Kidneys excrete urine into amniotic fluid by the third month
* Cloaca subdivides into rectum, anal canal, and urogenital sinus
Developmental Aspects
* Frequent micturition in infants due to small bladders and less-concentrated urine
* Incontinence is normal in infants: control of the voluntary urethral sphincter develops with the nervous system
* E. coli bacteria account for 80% of all urinary tract infections
* Streptococcal infections may cause long-term renal damage
* Sexually transmitted diseases can also inflame the urinary tract