Urinar S stem
Urinary System Organs: Kidneys
Filter 200 liters of blood daily, allowing toxins, metabolic wastes, and excess ions to leave the body in urine Regulate volume and chemical makeup of the Maintain the proper balance between water and salts, and acids and bases Produce renin to help regulate blood pressure and erythropoietin to stimulate red blood cell production Activate vitamin D
Other Urinary System Organs
Urinary bladd Urinary bladder er – provi provides des a temporary temporary stor storage age reservoir for urine – kidneys to the bladder
Urethra – trans Urethra transports ports urine from the bladder bladder out of the body
Other Urinary System Organs
Figure 1 Organs of the urinary system
Location and External Anatomy of the Kidneys
The bean-shaped kidneys lie in a retroperitoneal position in the superior lumbar r i n n x n fr m h lf h h r i the third lumbar vertebrae
The right kidney is lower than the left because it is crowded by the liver
Location and External Anatomy of the Kidneys
Figure 2 Position of the kidneys against the posterior body wall
Kidney: Associated Structures
A functionally unrelated adrenal gland sits atop each kidney
Three supportive tissues surround the kidney
Renal capsule – adheres to the kidney surface and prevents infections in surrounding regions from spreading to the kidneys
Adipose capsule/perirenal fat – cushions the kidney and helps attach it to the body wall
Renal fascia – dense fibrous connective tissue that anchors the kidney
Internal Anatomy of the Kidneys
A frontal section shows three distinct regions Cortex – the light colored, granular superficial region renal Medulla – exhibits cone-sha ed medullar pyramids
Pyramids are made up of parallel bundles of urinecollecting tubules Renal columns are inward extensions of cortical tissue that separate the pyramids
Renal pelvis – flat, funnel-shaped tube lateral to the hilus within the renal sinus
Internal Anatomy of the Kidneys
Figure 3 Diagrammatic view of the coronally sectioned kidney
Internal Anatomy of the Kidneys
Major calyces – large branches of the renal pelvis
Collect urine draining from papillae
Empty urine into the pelvis
Urine flows through the pelvis and ureters to the bladder
Blood and Nerve Supply
Approximately one-fourth (1200 ml) of systemic cardiac output flows through the kidneys each minute
Arterial flow into and venous flow out of the kidneys follow similar aths
The nerve supply is via the renal plexus
Figure 4 Summary of pathway of renal vasculature
The Nephron
Nephrons are the blood-processing units that form urine, consisting of:
Glomerulus – a tuft of capillaries associated with a renal tubule Glomerular (Bowman’s) capsule – blind, cupshaped end of a renal tubule that completely surrounds the glomerulus Renal corpuscle – the glomerulus and its Bowman’s capsule Glomerular endothelium – fenestrated (penetrated by many pores) epithelium that allows solute-rich, virtually protein-free filtrate to pass from the blood into the glomerular capsule
Anatomy of the Glomerular Capsule
The external parietal layer is a simple squamous epithelium The visceral layer consists of modified, branching, epithelial podocytes Extensions of the octopus-like podocytes terminate in foot processes Filtration slits – openings between the foot processes that allow filtrate to pass into the capsular space
The Nephron
Figure 5 Schematic view of a nephron depicting the structural characteristics of epithelial cells forming its various regions
Renal Tubule
Proximal convoluted tubule (PCT) – composed of cuboidal cells with numerous microvilli u – y reabsorbing water and solutes from filtrate) and mitochondria
Renal Tubule
Loop of Henle – a hairpin-shaped loop of the renal tubule
Proximal part is similar to the proximal convoluted u ue
Proximal part is followed by the thin segment (simple squamous cells) and the thick segment (cuboidal to columnar cells)
Distal convoluted tubule (DCT) – cuboidal cells without microvilli that function more in secretion than reabsorption
Renal Tubule
Figure 5 Schematic view of a nephron depicting the structural characteristics of epithelial cells forming its various regions
Collecting Tubules
The distal portion of the distal convoluted tubule nearer to the collecting ducts
Beginning late in the DCT, the tubule cells become heterogenous. Two important cell types are found
Intercalated cells
Cuboidal cells with microvilli Function in maintaining the acid-base balance of the body
Principal cells
Cuboidal cells without microvilli
Help maintain the body’s water and salt balance
Nephrons
Cortical nephrons – 85% of nephrons; located in the cortex
Juxtamedullar ne hrons:
Are located at the cortex-medulla junction
Have loops of Henle that deeply invade the medulla
Have extensive thin segments
Are involved in the production of concentrated urine
Nephrons
Figure 6 Detailed anatomy of nephron & their vasculature
Capillary Beds of the Nephron
Every nephron has two capillary beds
Glomerulus
Peritubular ca illaries
Each glomerulus is:
Fed by an afferent arteriole
Drained by an efferent arteriole
Capillary Beds of the Nephron
Blood pressure in the glomerulus is high because:
Afferent arterioles have larger diameters than efferent arterioles
Fluids and solutes are forced out of the blood into the glomerular capsule
Capillary Beds
Peritubular capillaries are low-pressure, porous capillaries adapted for absorption which:
Arise from efferent arterioles
Cling closely to renal tubules
Empty into the renal venous system
Vasa recta – long, straight efferent arterioles of juxtamedullary nephrons
Capillary Beds
Figure 7 Detail of juxtaglomerular apparatus of a nephron
Vascular Resistance in Microcirc Microcirculation ulation
Afferent and efferent arterioles offer high resistance to blood flow Blood pressure declines from 95 mm Hg in renal arteries to 8 mm Hg in renal veins
Protects glomeruli from fluctuations in systemic blood pressure
Resistance in efferent arterioles:
Reinforces high glomerular pressure
Reduces hydrostatic pressure in peritubular capillaries
Vascular Resistance in Microcirculation
Figure 8 Relative blood pressures in the renal circulation
Juxtaglomerular Apparatus (JGA)
Each nephron has a region called juxtaglomerular juxtaglomerul ar apparatus, where the initial portion of its coiling distal tubule lies against t e a erent an e erent arter o e. Arteriole walls have juxtaglomerular (JG) cells
Enlarged, smooth muscle cells
Have secretory granules containing renin
Act as mechanoreceptors that directly sense the blood pressure in the afferent arteriole
Juxtaglomerular Apparatus (JGA)
Macula densa
Tall, closely packed distal tubule cells
Lie adjacent to JG cells
Function as chemoreceptors or osmoreceptors that respond to changes in the solute content of the filtrate in the tubule lumen.
Mesanglial cells appear to control the glomerular filtration rate
Juxtaglomerular Apparatus (JGA)
Figure 9
Filtration Membrane
Filter that lies between the blood and the interior of the glomerular capsule
It is a porous membrane that allows free passage of
Composed of three layers
Fenestrated endothelium of the glomerular capillaries
Visceral membrane of the glomerular capsule (podocytes)
Basement membrane composed of fused basal laminas of the other layers
Filtration Membrane
Figure 10
Filtration Membrane
Figure 11 Diagrammatic view of a section through the f iltration membrane showing all three structural elements
Mechanism of Urine Formation
The kidneys filter the body’s entire plasma volume 60 times each day
The filtrate:
Contains all plasma components except protein Loses water, nutrients, and essential ions to become urine
The urine contains metabolic wastes and unneeded substances
Mechanism of Urine Formation
Urine formation and adjustment of blood composition major processes
Glomerular filtration
Tubular reabsorption
Secretion
Figure 12 The kidney depicted schematically as a single, large, uncoiled nephron
Glomerular Filtration
The glomerulus is more efficient than other capillary beds because:
permeable to water & solutes Glomerular blood pressure is higher It has a higher net filtration pressure
Glomerular Filtration
In general, the filtration membrane allows molecules smaller than 3 nm in diameter (eg: water, glucose, amino acids, and nitrogenous renal tubule – this causes the substances in the blood & the glomerular filtrate to be in the same concentration.
Large molecules (7-9 nm) are usually completely barred from entering the tubule.
Glomerular Filtration
Plasma proteins are not filtered and are used to maintain colloid osmotic (oncotic) pressure of the blood, preventing the lost of all of its water to t e rena tu u es.
The presence of proteins or blood cells in the urine usually indicates some problem with the filtration membrane
Net Filtration Pressure (NFP)
The pressure responsible for filtrate formation
Glomerular hydrostatic pressure (HPg) is opposed by forces that drive the fluid back into glomerular ill ri
These filtration-opposing forces are: 1. oncotic pressure of glomerular blood (OP g) 2. capsular hydrostatic pressure (HPc)
NFP equals the HPg (55 mm Hg) minus OPg (28-30 mm Hg) combined with the HPc (about 15 mm Hg) NFP = HPg – (OPg + HPc)
Net Filtration Pressure (NFP)
Figure 13 Forces that determine glomerular filtration and the eff ective filtration pressure
Glomerular Filtration Rate (GFR)
The total amount of filtrate formed per minute by the kidneys
GFR is directly proportional to the NFP
Changes in GFR normally result from changes in glomerular blood pressure
Regulation of Glomerular Filtration
If the GFR is too high:
If the GFR is too low:
Needed substances cannot be reabsorbed quickly enough and are lost in the urine Everything is reabsorbed, including wastes that are normally disposed of
Three mechanisms control the GFR
Renal autoregulation (intrinsic system) Neural controls The renin-angiotensin system
Intrinsic Controls Autoregulation entails two types of control
1.
Myogenic mechanism – responds to changes in pressure of the renal blood vessels;
-
increase systemic blood pressure causes the afferent arterioles to constrict, which restrict blood flow into the glomerulus.
-
a decline in systemic blood pressure causes dilation of afferent arterioles.
Intrinsic Controls 2.
Tubuloglomerular feedback mechanism is directed by the macula densa cells of the uxta lomerular a aratus: a) when macula densa cells are exposed to slowly flowing filtrate/ filtrate with low osmolarity, they permit vasodilatation of the afferent arterioles- more blood flow into the glomerulus, thus increasing the NFP and GFR.
Intrinsic Controls b) when the filtrate is flowing rapidly and/or it has a high sodium & chloride content (or high osmolarity), the macula densa cells releases the v and allowing more time for filtrate processing
- the macula macula densa cells also send messa messages ges to to the JG cells of the juxtaglomerular apparatus that set the renin-angiotensin mechanism into into motion.
Sympathetic Nervous System (SNS) Controls
When the SNS is at rest:
Renal blood vessels are maximally dilated Autoregulation mechanisms prevail
Under stress:
Epinephrine is released by the adrenal medulla (epinephrine interact with alpha adrenergic receptors on vascular smooth muscle causing constriction of afferent arterioles arter ioles – inhib inhibit it filtrate filtrate form formation ation - ind indire irectl ctly y trips trips reni reninnangiotensin mechanism by stimulating macula densa cells)
Sympathetic Nervous System (SNS) Controls
Norepinephrine is released by the SNS (norepinephrine binds with beta adrenergic receptors that stimu stimulates lates JG cells cells to release release renin – increa increase se system c oo pressure v a ren n-ang otens n mechanism)
Afferent arterioles constrict and filtration is inhibited
The SNS also stimulates the renin-angiotensin mechanism
Renin-Angiotensin Mechanism
Is triggered when the JG cells release renin
en n ac s on ang o ens nogen o re ease angiotensin I
Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE)
Renin-Angiotensin Mechanism
Angiotensin II (potent vasocontrictor):
Activates smooth muscle of arterioles throughout the body, causes mean arterial pressure to rise causes the renal tubule to reclaim more sodium ions from the filtrate)
As a result, both systemic and glomerular hydrostatic pressures rise, increase blood volume
Angiotensin causes the efferent arterioles to constrict to greater extent, thereby increasing the hydrostatic (blood) pressure- this defensive mechanism partially restores the GFR to normal levels.
Renin-Angiotensin Mechanism
Although the renin-angiotensin mechanism , main thrust is to stabilize the systemic blood pressure and extracellular fluid volume
Renin Release
Renin release is triggered by:
Reduced stretch of the granular JG cells- a drop in systemic BP < 80 mm Hg stretches the JG cells to release more renin
Stimulation of the JG cells by activated macula densa cells
Direct stimulation of the JG cells via β1-adrenergic receptors by renal nerves
Regulation of Glomerular Filtration
Figure 14 Flowchart indicating the mechanisms regulating the glomerular filtration rate (GFR) of kidneys. (+) indicates a stimulatory effects & (-) indicates an inhibitory eff ect
Tubular Reabsorption
A transepithelial process whereby most tubule contents are returned to the blood
Transported substances move through three membranes
Luminal and basolateral membranes of tubule cells
Endothelium of peritubular capillaries
K + and some Na+ are reabsorbed via paracellular pathways
Tubular Reabsorption
In healthy kidney, all organic nutrients are reabsorbed
Water and man ions reabsor tion are continuously regulated and adjusted in response to hormonal signal.
Reabsorption may be an active (requires ATP) or passive process
Sodium Reabsorption: Primary Active Transport
Sodium reabsorption is almost always by active transport
Na+ enters the tubule cells at the luminal membrane +
Na+-K + ATPase pump
From there it moves passively by diffusion to peritubular capillaries, due to:
Low hydrostatic pressure High osmotic pressure of the blood
Na+ reabsorption provides the energy and the means for reabsorbing most other solutes
Reabsorption of Water, Ions and Nutrients: Passive and Secondary Active Transport
In passive tubular reabsorption, substances move along their electrochemicals gradient without the use of ATP. pos ve y c arge so um ons move roug the tubule cells into the peritubular capillary blood, they establish an electrical gradient that favours the passive reabsorption of anions (Cl & HCO3-) into the peritubular capillaries to restore electrical neutrality in the filtrate & plasma
Reabsorption
Active pumping of Na+ drives reabsorption of:
Water by osmosis (water is “obliged” to follow salt, this sodium-linked water flow is referred to a obligatory water reabsorption)
Anions and fat-soluble substances by diffusion (as water present in the filtrate increase dramatically and if able, they too begin to follow their concentration gradients into the tubule cells - solvent drag – this explains why lipid-soluble drugs & environmental toxins are difficult to excrete)
Organic nutrients and selected cations by secondary active transport (‘push’ comes from the gradient created by Na +-K + pumping at the basolateral membrane) – glucose, amino acids, lactate, vitamins and most cations.
Reabsorption by PCT Cells
Figure 15 Reabsorption by PCT cells
Nonreabsorbed Substances
Substances are not reabsorbed if they:
Lack carriers
Are not lipid soluble
Are too large to pass through membrane pores
Urea (50-60% of urea present in the filtrate is reclaimed – small enough to diffuse through the membrane pores), creatinine (a large, lipidinsoluble molecule, is secreted to a small extent – not reabsorbed at all), and uric acid
Absorptive Capabilities of Renal Tubules and Collecting Ducts
1. Proximal convoluted tubule (PCT)- the most active “reabsorbers”
Substances reabsorbed in PCT include:
Sodium, all nutrients, cations, anions, and water rea an
p -so u e so utes
Small proteins
2. Loop of Henle
H2O, Na+, Cl−, K + (descending)
Ca2+, Mg2+, and Na+ (ascending)
Absorptive Capabilities of Renal Tubules and Collecting Ducts
3. Distal Convoluted Tubules (DCT) - only about 10% of the originally filtered NaCl & 20% of the water remain in the tubule
Na+-Cl- symporters absorb Na+ and Cl-, but most reabsor tion from this oint on de ends lar el on the need of the body at the time & is regulated by hormones If needed nearly all of the water and Na+ reaching DCT can be reclaimed in the presence of regulatory hormones (reabsorption of water depends on the presence of antidiuretic hormone)
Absorptive Capabilities of Renal Tubules and Collecting Ducts 4. Collecting duct
reabsorption of the remaining Na + is under control of hormone aldosterone and (indirectly) aldosterone promote water absorption (because as sodium is reabsorbed, water follows it back into the blood when possible) Aldosterone induce reabsorption of sodium which is coupled to potassium ion secretion (i.e. Na+ enters, K + diffuses into the lumen)
Tubular Secretion
Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate Some secretion (most importantly H+) occurs in the proximal tubule, but the late regions of the distal tubules and collecting duct are also active in secretion.
Tubular Secretion
Tubular secretion is important for:
Disposing of substances in the filtrate (certain drugs penicillin & phenobarbital) uric acid that have been reabsorbed by passive process
Ridding the body of excess potassium ions
Controlling blood pH
Tubular Secretion
Nearly all of the potassium ions in the urine are derived from active tubular secretion into collecting ducts under the influence of aldosterone because virtually all the K + present in the filtrate is reabsorbed in the PCT & ascending loop of Henle.
Tubular Secretion
When blood pH begins to drop toward the acid end of its homeostatic range, the renal tubule cells actively secrete H+ into the filtrate and retain more bicarbonate and potassium ions.
As a result, the blood pH rises & the urine drains off access acid.
Conversely, when blood pH approaches the alkaline end of its range, Cl- rather than HCO3- is reabsorbed and bicarbonate is allowed to leave the body in urine
A Summary of Renal Function
Formation of Dilute Urine
Filtrate is diluted in the ascending loop of Henle Dilute urine is created by allowing this filtrate to continue into the renal pelvis This will happen as long as antidiuretic hormone (ADH) is not being secreted Collecting ducts remain impermeable to water; no further water reabsorption occurs
Formation of Dilute Urine
Sodium and selected ions can be removed from filtrate by active and passive mechanisms by distal & collecting tubule cells so that the urine becomes more dilute
Formation of Concentrated Urine
Antidiuretic hormone (ADH) inhibits diuresis
It accomplishes this by increasing the number of water-filled channels in the principal cells of the collecting ducts so that water passes easily from cells into interstitial space.
This equalizes the osmolality of the filtrate and the interstitial fluid
In the presence of ADH, 99% of the water in filtrate is reabsorbed
ADH-dependent water reabsorption is called facultative water reabsorption
Formation of Concentrated Urine
Figure 18 The Effects of ADH on the DCT and Collecting Ducts
Renal Clearance
The volume of plasma that is completely cleared of a particular substance in a given time (usually in 1 minute) Renal clearance tests are used to:
Determine the GFR
Follow the progress of diagnosed renal disease
RC = UV/P RC = renal clearance rate 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
Inulin is often used as a standard to determine the GFR by renal clearance because it is not reabsorbed, stored, or secreted by the kidneys
Infused inulin is eliminated in urine, its renal c earance va ue s equa o .
Measured value for inulin are U= 125 mg/ml, V= 1 ml/min, and P= 1mg/ml. RC= (125 X 1)/1 =125 ml/min, meaning in 1 minute, the kidneys have removed (cleared) all the inulin present in 125 ml of plasma
Renal Clearance
A clearance value less than that of inulin means that substance is partially absorbed e.g. urea has a clearance value of 70 ml/min, meaning that of minute, approx. 70 ml is completely cleared of urea, while the urea in the remaining 55 ml is recovered & returned to the plasma.
In healthy individuals, glucose has clearance value of zero (reabsorption is complete)
Physical Characteristics of Urine
Color and transparency
Clear, pale to deep yellow (due to urochrome- a pigment that results from body destruction of emog o n
Concentrated urine has a deeper yellow color
Drugs, vitamin supplements, and diet can change the color of urine
Cloudy urine may indicate infection of the urinary tract
Physical Characteristics of Urine
Odor
Fresh urine is slightly aromatic Standing urine develops an ammonia odor due to bacterial metabolism of its urea solutes Some drugs and vegetables (asparagus) alter the usual odor, as do some diseases e.g. in diabetes mellitus the urine smells fruity because of its acetone content
Physical Characteristics of Urine
pH
Slightly acidic (pH 6) with a range of 4.5 to .
Diet can alter pH (4.5-8.0)- diet with large amount of protein and whole wheat– acidic urine
Vegetarian diet – alkaline urine
Physical Characteristics of Urine
Specific gravity
Specific gravity is the term used to compare the weight of substance to the weight of an equal vo ume o s e wa er Because urine is water plus solutes, its weights more than distilled water. Specific gravity of distilled water is 1.0
Urine - ranges from 1.001 to 1.035 Dependent on solute concentration
Chemical Characteristics of Urine
Urine is 95% water and 5% solutes
The largest component of urine by weight, apart from water, is urea. rogenous was es nc u e urea rea own o amino acids), uric acid (end product of nucleic acid metabolism), and creatinine (a metabolite of creatine phosphate)
Normal solute constitutes of urine, in order of deceasing concentration include urea, sodium, potassium, phosphate, sulfate ions, creatinine, and uric acid.
Chemical Characteristics of Urine
Other normal solutes include (much smaller but highly variable amounts):
Calcium, magnesium, and bicarbonate ions
Abnormally high concentrations of any urinary constituents may indicate pathology
Disease states alter urine composition dramatically
Ureters
Slender tubes that convey urine from the kidneys to the bladder
Ureters enter the base of the bladder throu h the posterior wall
distal ends closes as bladder pressure increases and prevents backflow of urine into the ureters
Ureters
Ureters have a trilayered wall
Mucosa- transitional epithelium, lamina propria
Muscularis – circular layer and longitudinal layer (smooth muscle sheets)
Fibrous connective tissue adventitia
Ureters actively propel urine to the bladder via response to smooth muscle stretch
Urinary Bladder
Smooth, collapsible, muscular sac that temporarily stores urine It lies retroperitoneally on the pelvic floor posterior to the pubic symphysis – u u inferiorly, lies immediately anterior to rectum.
Females – anterior to the vagina and uterus
Trigone – triangular area outlined by the openings for the ureters and the urethra
Clinically important because infections tend to persist in this region
Urinary Bladder
Figure 19 Structure of the urinary bladder & urethra
Urinary Bladder
The bladder wall has three layers
Transitional epithelial mucosa A thick muscular layer called the detrusor muscle rous a vent t a
The bladder is distensible and collapses when empty As urine accumulates, the bladder expands without significant rise in internal pressure A moderately full bladder can hold approx- 500 ml of urine (however if necessary it can hold more than double the amount)
Urethra
Muscular tube that:
Drains urine from the bladder Conveys it out of the body
not being passed
Internal urethral sphincter – involuntary sphincter at the bladder-urethra junction that keeps the urethra closed when urine is not being passed & prevents leaking of urine between voidings External urethral sphincter – voluntary sphincter surrounding the urethra as it passes through the urogenital diaphragm Levator ani muscle – voluntary constrictor of urethra
Urinary Bladder
Figure 19 Structure of the urinary bladder & urethra
Urethra
The length and functions of the urethra differ in the 2 sexes- in female the urethra is 3-4 cm , male approx 20 cm
The female urethra is tightly bound to the anterior vaginal wall
Its external opening, the external urethral orifice lies anterior to the vaginal opening and posterior to the clitoris
Urethra
The male urethra has three named regions
Prostatic urethra – runs within the prostate gland – diaphragm
Spongy urethra – passes through the penis and opens via the external urethral orifice
Urethra
Figure 19
Micturition (Voiding or Urination)
The act of emptying the bladder
Usually when about 200 ml of urine has accumulated, distension of the bladder walls activates stretch recep ors, r gger ng a v scera re ex arc.
Afferent (sensory) impulse are transmitted to the sacral region of the spinal cord, & efferent impulses return to the bladder via the parasympathetic pelvic splanchnic nerves causing the detrusor muscle to contract & internal sphincter to relax.
Micturition (Voiding or Urination)
As the contraction increase in intensity, they force stored urine through the internal sphincter into the upper part of the urethra eren mpu ses are a so ransm e o e brain, so one feels the urge to void at this point
Because the external sphincter (and the levator ani) is voluntarily controlled, we can choose to keep it closed & postpone bladder emptying temporarily
Micturition (Voiding or Urination)
When one choose not to void, reflex bladder contraction subside within a minute or so and urine continue to accumulate.
After 200-300 ml more has collected, micturition reflex occurs again and if urination is delayed again, is damped once more.
The urge of void becomes irresistible and micturition occurs, whether one wills it or not