1. Urinary System 201656036 Suhui Seong
Urine is formed by nephrons in the kidneys
The kidneys reabsorb salt and water from the filtrate
The kidneys maintain homeostasis of plasma composition
The kidneys maintain homeostasis of plasma electrolytes and pH
Physiology in health and disease

2. Urine is formed by nephrons in the kidneys
Gross structure of the urinary system
The paired kidneys lie on either side of the vertebral column below the diaphragm and liver. Each adult kidney weighs about 160 g and is about 11 cm (4 in.) long and 5 to 7 cm (2 to 3 in.) wide—about the size of a fist.
Urine produced in the kidneys is drained into a cavity known as the renal pelvis ( = basin) and then is channeled from each kidney via long ducts—the ureters —to the urinary bladder
비뇨기계의 구조
The organs of the urinary system.
The urinary system of a female is shown; that of a male is the same, except that the urethra runs through the penis.

3. Gross structure of the urinary system
<The structure of a kidney>
(a) A coronal section of a kidney
( b ) A magnified view of the contents of a renal pyramid
( c ) A single nephron tubule
Renal
cortex
medulla
Nephron
Ureter
Renal cortex
Renal medulla
Minor calyx
Major calyx
Proximal convoluted tubule
Loop of Henle
Renal pyramid
Renal column
Renal pelvis
Renal papilla
Glomerular capsule
Distal
convoluted
tubule
Collecting
duct
A coronal section of the kidney shows two distinct regions.
The outer cortex is reddish brown and granular in appearance because of its many capillaries.
The deeper region, or medulla, is striped in appearance due to the presence of microscopic tubules and blood vessels.
The medulla is composed of 8 to 15 conical renal pyramids separated by renal columns.
The cavity of the kidney is divided into several portions.
Each pyramid projects into a small depression called a minor calyx (the plural form is calyces ).
Several minor calyces unite to form a major calyx.
The major calyces then join to form the funnel-shaped renal pelvis.
The renal pelvis collects urine from the calyces and transports it to the ureters and urinary bladder.
비뇨기계의 구조

4. Gross structure of the urinary system
The urinary bladder is a storage sac for urine, and its shape is determined by the amount of urine it contains.
The urinary bladder is drained inferiorly by the tubular urethra.
Urethra
Female : 4 cm (1.5 in.) long and opens into the space between the labia minora.
Male : about 20 cm (8 in.) long and opens at the tip of the penis, from which it can discharge either urine or semen.
A pseudocolor radiograph of the urinary system.

5. Control of Micturition
The urinary bladder has a muscular wall known as the detrusor muscle.
This muscle can generate action potentials in response to stretch, but it also receives parasympathetic axons, which release acetylcholine (Ach) to stimulate contraction and thus emptying of the bladder.
→ Therefore, newer drugs that block specific muscarinic ACh receptors in the bladder are now available to treat an overactive bladder (detrusor muscle).
Two muscular sphincters surround the urethra.
- Upper sphincter(= internal urethral sphincter) : smooth muscle
- Lower sphincter(= external urethral sphincter) : voluntary skeletal muscle
The actions of these sphincters are regulated in the process of urination, which is also known as micturition.
Micturition is controlled by a reflex center in the sacral regions of the spinal cord.
Filling of the urinary bladder activates stretch receptors, which send action potentials to the micturition center.
The micturition center then activates parasympathetic neurons,
which produce (1) contractions of the detrusor muscle
(2) relaxation of the internal urethral sphincter.

6. CLINICAL APPLICATION
Kidney stones are composed of crystals (of calcium oxalate, calcium phosphate, and other substances) and proteins that grow until they break loose and pass into the urine collection system.
When a stone breaks loose and passes into a ureter, it produces steadily increasing pain, which can become so intense that the patient requires narcotic drugs.
The calcium and other substances in kidney stones are normally present in urine, but they become supersaturated and crystalize to form stones for reasons not currently understood.
The stones may be removed surgically or broken up by a noninvasive procedure called shock-wave lithotripsy.
Kidney stones form from crystals created by waste chemicals
Kidney stone
Kidney stones
Kidney stones
Uretur stone

7. The distal tubules are located in the renal cortex. Nephron
The distal convoluted tubule receives fluid from the ascending limb of the loop of Henle.
The distal tubules are located in the renal cortex.
Nephron
The functional unit of the kidney responsible for the formation of urine.
Glomerulus, Glomerular capsule, renal tubule(Proximal and distal convoluted tubule, Henle loop, collecting duct)
The glomerular (Bowman’s) capsule surrounds the glomerulus and is the bulbous beginning portion of the tubule that first receives the filtrate from plasma.
All glomerular capsules are located in the renal cortex.
The proximal convoluted tubule receives the filtrate from the glomerular capsule.
The proximal tubules are also located in the renal cortex..
The collecting duct receives fluid from the distal convoluted tubules of several nephrons.
Each collecting duct thus begins in the cortex and then descends into the medulla.
The collecting ducts end at the tip of the renal pyramids, so that they can empty their urine into the calyces..
The loop of Henle receives fluid from the proximal tubule.
The first portion of the loop, the descending limb, takes the fluid from the cortex into the medulla; the second portion of the loop, the ascending limb, returns to the cortex.
The nephron tubules and associated blood vessels.
The blood flow from a glomerulus to an efferent arteriole, to the peritubular capillaries, and to the venous drainage of the kidneys is indicated with arrows.

8. Urethra

9. Glomerular filtrate enters the renal tubules
Endothelial cells of the glomerular capillaries have large pores called fenestrae.
As a result of these large pores, glomerular capillaries are 100 to 400 times more permeable to plasma water and dissolved solutes than are the capillaries of skeletal muscles. (red blood cells, white blood cells, and platelets: X)
Before the fluid in blood plasma can enter the interior of the glomerular capsule, it must pass through three layers that could serve as selective filters.
Potential filtration barrier
Capillary fenestrae
- Large enough to allow proteins to pass but are surrounded by charges that may present some barrier to plasma proteins.
2. Glomerular basement membrane
Glycoproteins lying immediately outside the capillary endothelium.
3. Slit diaphragm
- Inner (visceral) layer of the glomerular capsule
1.Capillary fenestrae
2.Glomerular basement membrane
3.Slit diaphragm
Podocyte foot process

10. Glomerular utrafiltrate The protein concentration
Glomerular Ultrafiltrate : The fluid that enters the glomerular capsule
The force favoring filtration is opposed by a counterforce developed by the hydrostatic pressure of fluid in the glomerular capsule.
The protein concentration
- Tubular fluid : low (2-5 mg/100 ml)
Plasma fluid : high (6 -8 g/100 ml)
→ The greater colloid osmotic pressure of plasma promotes the osmotic return of filtered water.
Net filtration pressure : 10 mmHg
Glomerular filtration rate (GFR)
Volume of filtrate produced by both kidneys per minute.
GRF averages : ml/min
= 7.5 L/hr = 180 L/day
(Total blood volume : 5.5 L
→ Total blood volume is filtered into the urinary tubules every 40 minuts)

11. The kidneys reabsorb salt and water from the filtrate
Reabsorption in the proximal tubule
Although about 180 L of glomerular ultrafiltrate are produced each day, the kidneys normally excrete only 1-2 L of urine in a day (1 %).
Obligatory water loss
- 400 ml of urine/day (minimum needed to excrete the metabolic wastes produced by the body)
Reabsorption
- The return of filtered molecules from the tubules to the blood.

12. Salt and water reabsorption in the proximal tubule
The Na+ /K+ (ATPase) pumps responsible for this active transport maintain a low Na+ concentration in the cytoplasm.
As a results, Na+ continuously diffuses from the glomerular filtrate into the cytoplasm, and is then pumped into the surrounding interstitial fluid and plasma.
Cl- follows the Na+ passively by electrical attraction from the glomerular filtrate into the surrounding interstitial fluid and plasma.
The net effect is an increase in the salt (NaCl) concentration of the interstitial fluid and the blood plasma of the peritubular capillaries.
The higher NaCl concentration of the fluid surrounding the proximal tubules serves as an osmotic gradient.
Because the walls of the proximal tubules are permeable to water, water follows the NaCl into the interstitial fluid and then into the peritubular capillaris.

13. Significance pf proximal tubule reabsorption
Approximately 65% of glomerular filtrate is immediately reabsorbed across the proximal tubule.
An additional smaller amount of water (about 20 % of the filtrate) is also reabsorbed constantly across the descending limb of the loop of Henle
→ About 85 % of the glomerular filtrate is always reabsorbed in the earlier parts of the nephrons.
This reabsorption is very costly in terms of energy expenditures, accounting for as much as 6% of the calories consumed by the body at rest.
Only 15% of the initial filtrate remains to enter the distal convoluted tubule and collecting duct.
This is still a large volume of fluid that must be reabsorbed to varying degrees in accordance with the body’s state of hydration.
This “fine tuning” of the percentage of reabsorption and urine volume is accomplished by the action of hormones on the later regions of the nephron.
15% GFR (180 L/day) = 27 L/day

14. The loop of Henle produces a hypertonic renal medulla
Ascending limb
Pumps out NaCl into the surrounding interstitial fluid of the renal medulla.
Not permeable to water
→ As a result, the interstitial fluid becomes hypertonic while the filtrate that ascends into the distal tubule in the renal cortex becomes hypotonic.
2. The blood vessels in the renal medulla also form loops (= vasa recta), which allow them to carry away water but leave the NaCl to accumulate in the interstitial fluid of the medulla.
3. A countercurrent multiplier system
Interactions between the descending and ascending limbs.
Operates to increase the concentration of the renal medulla.
The ascending limb produces the hypertonic medulla by pumping out salt. This draws water from the descending limb, producing a hypertonic filtrate that arrives at the ascending limb, which then allows it to pumb out even more NaCl.

15. The role of urea in urine concentration
Urea : waste product of the metabolism of amino acid (produced by the liver)
Urea also contributes to the hypertonic concentration of the medulla.
In the inner medulla,
Urea diffuses out of the inner collecting duct into the interstitial fluid.
(2) It can then pass into the ascending limb of the loop of Henle, so it recirculates in the interstitial fluid of the renal medulla. The urea and NaCl in the interstitial fluid of the renal medulla make it very hypertonic.
Thus, (3) water leaves the collecting duct by osmosis

16. Water reabsorption from the collecting duct requires ADH
As a result of active NaCl transport and countercurrent multiplication between the ascending and descending limbs and the recycling of urea between the collecting duct and the loop of Henle, the interstitial fluid is made very hypertonic.
The fluid surrounding the collecting ducts in the medulla : Hypertonic
The fluid that passes into the collecting ducts in the cortex
: Hypotonic
The wall of the collecting duck
NaCl (impermeable)
Water (permeable)
→ Water is drawn out by osmosis
In this way, most of the water remaining in the filtrate is returned to the vascular system.

17. ADH stimulation of aquaporin channels
The osmotic gradient created by the countercurrent multiplier system
→ Provides the force for water reabsorption through the collecting ducts.
The rate of osmosis across the walls of the collecting ducts : permeability of water.
→ The number of aquaporins (water channels) in the plasma membranes of the collecting duct epithelial cells.
(a) When ADH is absent, aquaporin channels are located in the membrane of intracellular vesicles within collecting duct epithelial cells.
(b) ADH stimulates the fusion of these vesicles with the plasma membrane and (c) the insertion of the aquaporin channels into the plasma membrane.
(d) When ADH is withdrawn, the plasma membrane pinches inward (in endocytosis) to again form an intracellular vesicle and to remove the aquaporin channels from the plasma membrane.

18. Homeostasis of plasma concentration is maintained by ADH
In dehydration,
a rise in ADH secretion results in a reduction in the excretion of water in the urine.
In overhydration,
the excess water is eliminated through a decrease in ADH secretion.
These changes provide negative feedback corrections, maintaining homeostasis of plasma osmolality and, indirectly, blood volume.

19. CLINICAL APPLICATION
Diabetes insipidus is characterized by polyuria (a large urine volume—from 3 to 10 L per day), thirst, and polydipsia (drinking a lot of fluids).
The urine is dilute, with a hypotonic concentration of less than 300 mOsm.
There are two major types of diabetes insipidus
central diabetes insipidus, caused by inadequate secretion of ADH (arginine vasopressin)
(2) nephrogenic diabetes insipidus, caused by the inability of the kidneys to respond to ADH.
These two types can be distinguished by measuring plasma arginine vasopressin, and by challenging the kidneys with a synthetic ADH called desmopressin. Nephrogenic diabetes insipidus may be caused by genetic defects in either the aquaporin channels or the ADH receptors.
More commonly, it is acquired as a response to drug therapy (from lithium given to treat bipolar disorder, and from certain antibiotics) or other causes.
People with central diabetes insipidus can take desmopressin when needed, and those with nephrogenic diabetes insipidus must drink a lot of water to prevent dehydration.

20. The kidneys clear certain molecules from the plasma
The kidneys maintain homeostasis of plasma composition
The kidneys clear certain molecules from the plasma
Excretion rate
= (filtration rate + secretion rate) - reabsorption rate
Renal clearance : The ability of the kidneys to remove molecules from the blood plasma by excreting them in the urine.
Secretion (membrane transport process) : the opposite of reabsorption
→ The process of reabsorption decreases renal clearance,
The process of secretion increases renal clearance.
Molecules and ions (peritubular capillaries) → the interstitial fluid → the basolateral membrane of the tubular epithelial cells → the lumen of the nephron tubule.

21. Inulin is filtered, but neither reabsorbed nor secreted
The renal clearance of inulin.
( a ) Inulin is present in the blood entering the glomeruli.
( b ) some of this blood, together with its dissolved inulin, is filtered.
All of this filtered inulin enters the urine, whereas most of the filtered water is returned to the vascular system (is reabsorbed).
( c ) The blood leaving the kidneys in the renal vein, therefore, contains less inulin than the blood that entered the kidneys in the renal artery.
Because inulin is filtered but neither reabsorbed nor secreted,
Inulin clearance rate = Glomerular filtration rate (GFR)

22. Inulin is filtered, but neither reabsorbed nor secreted
For example,
Inulin is infused into a vein
its conc. in the urine
= 30 mg/mL
its conc. in the plasma
= 0.5 mg/mL
The rate of urine formation
= 2 ml/min
the GFR can be calculated as:
Because inulin is neither reabsorbed nor secreted,
the amount filtered equals the amount excreted:

23. Penicillin and PAH are secreted by the nephrons
For compounds in the unfiltered renal blood to be cleared, they must be secreted into the tubules by active transport from the peritubular capillaries.
In this way, all of the blood going to the kidneys can potentially be cleared of a secreted compound in a single pass.
This is the case for an exogenous molecule called para-aminohippuric acid (PAH), which can be infused into the blood.
All of the PAH entering the peritubular capillaries is secreted by carriers of the organic anion transporter family (previously discussed) into the filtrate of the proximal tubule.
PAH
Filtration
To peritubular
capillaries
All of the blood leaving the kidneys is free of PAH (d) .
The clearance of PAH therefore equals the total renal blood flow.
The PAH present in the unfiltered blood is secreted from the peritubular capillaries into the nephron (c) . 11
Some of PAH in glomerular blood (a) is filtered into the glomerular capsules (b).

24. Aldosterone stimulates Na+ reabsorption and K+ secretion
The kidneys maintain homeostasis of plasma electrolytes and pH
Aldosterone stimulates Na+ reabsorption and K+ secretion
Sodium Reabsorption
About 90% of the Na+ that enters the filtrate is reabsorbed across the walls of the poximal tubules and ascending limbs of the loops, leaving 10% to enter the distal tubules and collecting ducts.
Aldosterone stimulates the last part of the distal tubule and cortical collecting duct (the portion of the collecting duct in the renal cortex) to reabsorb the remaining Na+.
The reansorption of Na+ is accompanied by Cl- and water retention.
Without aldosterone, most of this r der (8% of the original amount filtrated) will be reabsorbed in the later regions of the nephron.
This leaves 2% of the filtrated Na+ to be excreted in the urine, which is still a rather large amount (averaging 30g/day).
Under maximum aldosterone stimulation, all of the Na+ will be reabsorbed, so that none is excreted in the urine.

25. Aldosterone stimulates Na+ reabsorption and K+ secretion
Potassium secretion
About 90% of the filtered potassium is reabsorbed in the early regions of the nephron (mainly from the proximal tubule).
In order for potassium to appear in the urine, it must be secreted into later regions of the nephron tubule.
Secretion of potassium occurs in the parts of the nephron that are sensitive to aldosterone—that is, in the late distal tubule and cortical collecting duct.
Potassium is reabsorbed and secreted.
K+ is almost completely reabsorbed in the proximal tubule, but under aldosterone stimulation it is secreted into the cortical portion of the collecting duct. .
→ All of the K+ in urine is derived from secretion rather than from filtration.

26. Control of aldosterone secretion
Because aldosterone promotes Na+ retention and K+ loss, one might predict (on the basis of negative feedback) that aldosterone secretion would be increased when there was a low Na+ or a high K+ concentration in the blood.
A rise in plasma K+ concentration depolarizes the aldosterone-secreting cells of the adrenal cortex, directly stimulating aldosterone secretion.
Juxtaglomerular apparatus

27. Control of aldosterone secretion
Juxtaglomerular apparatus
- The region in each nephron where the afferent arteriole comes into contact with the last portion of the thick ascending limb of the loop.
Granular cells within the afferent arteriole
Secrete the enzyme renin into the blood
The secretion of renin into the plasma by the granular cells of the juxtaglomerular apparatus thereby results in the increased production of angiotensin II.
Angiotensin II stimulates the adrenal cortex to secrete aldosterone.
Thus, secretion of renin from the granular cells of the juxtaglomerular apparatus initiates the renin-angiotensin-aldosterone system.
Increased renin secretion cause increased aldosterone secretion and, by this means, promote the reabsorption of Na+ from cortical collecting duct into the blood.
Angiotensin converting enzyme (ACE)
↓ ↓
Angiotensinogen → Angiotensin I → Angiotensin II
Renin

28. The kidneys can excrete H+ and reabsorb bicarbonate
The plasma K+ concentration indirectly affects the plasma pH.
Changes in plasma pH likewise affect the K+ concentration of the blood.
When the extracellular H+ concentration increases, some of the H+ moves into cells and causes cellular K+ to diffuse outward into the extracellular fluid.
The plasma concentration of H+ is thus decreased while the K+ increases, helping to reestablish the proper ratio of these ions in the extracellular fluid.
Fig. In the cells of the late distal tubule and cortical collecting duct, positively charged ions (K+ and H+) are secreted in response to the negative polarity produced by reabsorption of Na+.
Acidosis increases the secretion of H+ and reduces the secretion of K+ into the filtrate.
Acidosis may thus be accompanied by a rise in blood K+.
Alkalosis increases the renal secretion of K+ into the filtrate, and thus the excretion of K+ in the urine.

29. The kidneys can excrete H+ and reabsorb bicarbonate
The kidneys help regulate the blood pH by excreting H+ in the urine (mostly in buffered form, as described shortly) and by reabsorbing bicarbonate.
Because the kidneys normally reabsorb almost all of the filtered bicarbonate and excrete H+, normal urine contains little bicarbonate and is slightly acidic (pH5-7).
The apical membranes of the tubule cells (facing the lumen) are impermeable to bicarbonate. The reabsorption of bicarbonate must therefore occur indirectly.
In order for more H+ to be excreted, the acid must be buffered.
Bicarbonate cannot serve this buffering function because it is normally completely reabsorbed.
Acidification of the urine.