1. Physiology of the Kidneys
Chapter 17
(Pages: )
Structure and Function of the Kidneys
Glomerular Filtration
Reabsorption of Salt and Water
Renal Plasma Clearance
Renal Control of Electrolyte and Acid-Base Balance
Clinical Applications

2. Structure and Function of the Kidneys
Functions
The primary function of the kidneys is regulation of the extracellular fluid (plasma and interstitial fluid) environment in the body through the formation of urine (a modified filtrate of plasma).
Regulation of the volume of blood plasma (and thus the blood pressure).
Regulation of the concentration of waste products in the plasma.
Regulation of the concentration of electrolytes in the plasma.
Regulation of the pH of plasma.

3. II. Gross Structure of the Urinary System (Fig. 17.1 page 582)
Paired kidneys lie on either side of the vertebral column below the diaphragm and liver.
Renal pelvis is a cavity where urine produced in the kidneys is drained.
2 long ducts called the ureters which channel the urine into the
Urinary bladder that stores the urine until voided. It is drained inferiorly
by the tubular
Urethra.
Note: In human females, the urethra is 4 cm long and opens into the space
between the labia minora.
In human males, the urethra is about 20 cm long and open at the tip
of the penis, from which it can discharge
either urine or semen.

4. Figure 17.1 The organs of the urinary system.
The urinary system of a female is shown; that of a male is the same,
except that the urethral runs through the penis.

5. A coronal section of the kidneys (Fig. 17.2 page 583)
Shows that it is divided into an outer cortex and inner medulla.
The medulla is composed of renal pyramids, separated by renal columns.
The renal pyramids empty urine into the calyces that drain into the renal pelvis.
Then urine flows into the ureter and is transported to the bladder to be stored.
The ureter undergoes peristalsis, a wavelike contractions similar to those that occur in the digestive tract.

7. Control of Micturition
Micturition is the process of urination.
Controlled by 2 sphincters surround the urethra:
The upper internal urethral sphincter is composed of smooth muscle.
The lower external urethral sphincter is composed of skeletal muscle.
The urinary bladder has a muscular wall (detrusor muscle).
Numerous gap junctions interconnects the smooth muscle cell so that action potentials can spread from cell to cell.
Action potentials can be generated:
Automatically and in response to stretch, or by
Neural stimulation of parasympathetic neurons that innervate the muscle.

8. 2 reflexes results when the bladder is filling:
Guarding reflex to prevents the involuntary emptying of the bladder.
Voiding reflex to cause rhythmic contractions of bladder muscle and relaxation of the internal urethral sphincter. Sensory information passes up the spinal cord to the pons, where a group of neurons functions as a micturition center which activates the parasympathetic to the detrusor muscle, causing rhythmic contractions. The person feels sense of urgency but normally still has voluntary control over the external urethral sphincter.
Incontinence would occur at a particular bladder volume unless higher brain regions inhibited the voiding reflex.

10. III. Microscopic Structure of the Kidney (Fig. 17.4 & 17.5 page 585)
Each kidney contains more than a million microscopic functional units called nephrons responsible for the formation of urine.
A nephron consists of small tubes, or tubules, and associated small blood vessels.
Fluid formed by capillary filtration enters the tubules and is subsequently modified by transport processed; the resulting fluid that leaves the tubules is urine.

13. Renal Blood Vessels (Fig. 17.5 page 585)
Renal artery: is a branch from aorta .
Interlobar arteries: branches of the renal artery that pass between the pyramids through the renal columns.
Arcuate arteries: branches from the intelobar arteries at the boundary of the cortex and medulla.
Interlobular arteries: radiate from the arcuate arteries.
Afferent arteriole: subdivision of interlobular arteries.
Glomeruli: capillary network branches from the afferent arteriole, produces a blood filtrate that enters the urinary tubules.

14. Efferent arteriole: collects the remaining blood in glomerulus and
delivers it into
Peritubular capillaries: surround the renal tubules, and drain the
blood into veins.
9. Interlobular veins
10. Arcuate veins
11. Interlobar veins
Renal vein: a single vein formed from the interlobar veins that
descend between the pyramids, converge, and leave the
kidney to empties the blood into the inferior vena cava.

15. Nephron Anatomy

16. Nephron Tubules (Fig. 17.5 page 585)
Consists of:
Glomerular (Bowmann’s) capsule: Surrounds the glomerulus.
Together with glomerulus are located in the cortex of the kidney and constitute
the renal corpuscle.
The capsule contains an inner visceral layer of epithelium around the glomerulus
capillaries and an outer parietal layer. The space between them is continuous with
the lumen of the tubule and receives the glomerular filtrate.
Proximal convoluted tubule: Receives the filtrate from glomerular capsule.
Their wall consists of a single layer of cuboidal cells containing millions of microvilli
which increase the surface area for reabsorption.
Nephron loop (Loop of Henle): The fluid from the proximal tubule passes into the
medulla in the descending limb of the loop and returns to the cortex in the
ascending limb of the loop.
Distal convoluted tubules: Shorter than the proximal tubule.
Has relatively few microvilli.
Terminates as it empties into a collecting duct.
Collecting duct: Receives fluid from the distal tubules of several nephrons.
This fluid is the urine that passes into a minor calyx and is then funneled through the
renal pelvis and out of the kidney in the ureter.

20. 1.Glomerular filtration 2.Tubular reabsorption 3.Tubular secretion
There are 2 types of nephrons according to their position in the kidney and the length of their loops of Henle:
Juxtamedullary nephrons: Originate in the inner one-third of the cortex.
Are next to the medulla.
Have long nephron loops.
Play an important role in the ability of the
kidney to produce a concentrated urine.
Cortical nephrons: Originate in the outer two-third of the cortex.
Have shorter nephron loops than the juxtamedullary
nephrons.
Urine production requires 3 distinct processes:
1.Glomerular filtration
2.Tubular reabsorption
3.Tubular secretion

21. Processes in Urine Formation

23. Glomerular Filtration
The fluid that enters the glomerular capsule is called filtrate or ultrafiltrate because it is formed under pressure (the hydrostatic pressure of the blood).
The glomerular capillaries have large pores in their walls, and the layer of Bowman's capsule in contact with the glomerulus has filtration slits.
Water, together with dissolved solutes, can thus pass from the blood plasma to the inside of the capsule and the nephron tubules.
The glomerular filtration rate (GFR) is the volume of filtrate produced by both kidneys /minute.
The GFR averages 115 ml/minute in women and 125 ml/minute in men.
This is equivalent to 7.5 L/Hour or 180 L/Day (about 45 gallons)!
Since the total blood volume averages about 5.5 L, the means that the total blood volume is filtered into the urinary tubules every 40 minutes.
Most of the filtered water must obviously be returned immediately to the vascular system or a person would literally urinate to death within minutes.

27. Regulation of Glomerular Filtration Rate (Table 17.1 Page 590)
GFR is affected by:
Vasoconstriction or dilation of afferent arterioles affects the rate of blood flow to the glomerulus, and thus affects the GFR.
Changes in the diameter of the afferent arterioles that result from extrinsic and intrinsic regulatory mechanisms. These mechanisms are needed to ensure that the GFR will be high enough to allow the kidneys to eliminate wastes and regulate blood pressure, but not so high as to cause excessive water loss.
Reabsorption of Salt and Water (Figure Page 591)
The reabsorption of water from the glomerular filtrate occurs by osmosis, which results from the transport of Na+ and Cl- across the tubule wall.
The proximal tubule reabsorbs mot of the filtered salt and water, and most of the remainder is reabsorbed across the wall of the collecting duct under antidiuretic hormone (ADH) stimulation. When the concentration of ADH is increased, the collecting ducts become more permeable to water and more water is reabsorbed.

31. Although about 180L of glomerular ultrafiltrate are produced each day, the kidneys normally excrete only 1-2 L of urine in a 24-hour period.
Approximately 99% of the filtrate must thus be returned to the vascular system while 1% is excreted in the urine.
The urine volume varies according to the needs of the body.
When a well-hydrated person drinks a liter or more of water, urine production increases to 16 ml/minute (the equivalent of 23 L/day if this were to continue for 24 hours).
In severe dehydration, when the body needs to conserve water, only 0.3 ml of urine/minute , or 400 ml of urine/day, are produced.
A volume of 400 ml of urine/day is the minimum needed to excrete the metabolic wastes produced by the body; this is called the
obligatory water loss.
The return of filtered molecules from the tubules to the blood is called reabsorption.
About 85% of the 180L of glomerular filtrate formed/day is reabsorbed in a constant, unregulated fashion by the proximal tubules and descending limbs of the nephron loops.
The unregulated and regulated reabsorption of the filtrate occurs by osmosis.

32. Reabsorption in the Proximal Tubule
Because all plasma solutes, with the exception of proteins, are able to enter the glomerular ultrafiltrate freely, the total solute concentration (osmolality) of the filtrate is essentially the same as that of the plasma. Thus, the filtrate is isosmotic with the plasma. Reabsorption by osmosis cannot occur unless the solute concentrations of plasma in the peritubular capillaries and the filtrate are altered by active transport process which is achieved by the active transport of Na+ from the filtrate to the peritubular blood.

33. Renal Plasma Clearance
One of the major functions of the kidneys is to clear the blood from excess ions and waste products and excrete them in the urine. Because of renal clearance, the concentrations of these substances in the blood leaving the kidneys (in the renal vein) is lower than their concentrations in the blood entering the kidneys (in the renal artery).
Transport Process Affecting Renal Clearance
Renal clearance refers to the ability of the kidneys to remove molecules from the blood plasma by excreting them in the urine. Molecules and ions dissolved in the plasma can filtered through the glomerular capillaries and enter the glomerular capsules. Then, those that are not reabsorbed will be eliminated in the urine; they will be “cleared” from the blood.

34. Processes that affect renal clearance are: (Figure 17.21 page 599)
Filtration: Bulk transport through capillaries that promotes renal clearance.
Reabsorption: Movement of particular molecules and ions from the filtrate into the blood. It involves membrane transport by carrier proteins, and it reduces the renal clearance of these molecules from the blood.
Secretion: Is the opposite of reabsorption. Secreted ,molecules and ions move out of the peritubular capillaries into the interstitial fluid, and then are transported across the basolateral membrane of the tubule. Secretion increases renal clearance.

35. Molecules that are both filtered and secreted are thus cleared from the blood and eliminated in the urine more rapidly than molecules that are not secreted.
Excretion rate = (filtration rate + secretion rate) – reabsorption rate
This equation is used to measure the glomerular filtration rate (GFR) which is the volume of blood plasma filtered/minute by the kidneys.
Measurement of the GFR is very important in assessing the health of the kidneys.

38. Reabsorption of Glucose (Figure 17.24 page 603)
Glucose and amino acids in the blood are easily filtered by the glomeruli into the renal tubules.
These molecules are not present (above trace amounts) in normal urine, indicating that they must be completely reabsorbed.
This occurs in the proximal tubule by secondary active transport, which is mediated by membrane carriers that cotransport glucose and Na+, or amino acids and Na+.

39. Glycosuria
Glycosuria is a condition when glucose appears in the urine.
When more glucose passes through the tubules than can be reabsorbed.
Occurs when plasma glucose concentration is above mg/100 ml (the renal plasma threshold for glucose), in cases of hyperglycemia.
Renal plasma threshold is the minimum plasma concentration of a substance that results in the excretion of that substance in the urine.
Fasting hyperglycemia is caused by the inadequate secretion or action of insulin.
When hyperglycemia results in glycosuria, the disease is called diabetes mellitus.
A person with uncontrolled diabetes mellitus also excretes a large volume of urine because the excreted glucose carries water with it as a result of the osmotic pressure it generates in the tubules.
In a person with diabetes insipidus, large volume of dilute urine is excreted as a result of inadequate ADH secretion.

41. Renal Control of Electrolyte and Acid-Base Balance
The kidneys regulate the blood concentrations of Na+ , K+ , HCO3-, and H+
and thereby are responsible for maintaining the homeostasis of plasma electrolytes and the acid-base balance.
The kidneys help regulate the concentrations of plasma electrolytes by matching the urinary excretion of these compounds to the amounts ingested.
For example; the reabsorption of sulfate and phosphate ions across the walls of the proximal tubules is the primary determinant of their plasma concentrations. PTH secretion, stimulated by a fall in plasma Ca2+, acts on the kidneys to decrease the reabsorption of phosphate.
The control of Na+ is important in the regulation of blood volume and pressure; the control of K+ is required to maintain proper function of cardiac and skeletal muscles.

42. Action of aldosterone, the principal mineralocorticoid secreted by the adrenal cortex:(Figure and Table 17.6 page 607)
Stimulates renal reabsorption of Na+ and secretion of K+ in the late distal tubule and cortical collecting duct.
Its secretion is stimulated directly by a rise in blood K+ and indirectly by a fall in blood volume.
A fall in the blood volume (resulted from decreased plasma Na+) activates the renin-angiotensin-aldosterone system as follows:
a. Decreased blood flow and pressure through the kidneys stimulates the
secretion of the enzyme renin from the juxtaglomerular apparatus.
b. Renin catalyzes the formation of angiotensin I, which is then converted to
angiotensin II.
c. Angiotensin II stimulates the adrenal cortex to secrete aldosterone.
It stimulates the secretion of H+, as well as K+, into the filtrate in exchange for Na+ .
The nephrons filter HCO3- and reabsorb the amount required to maintain acid-base balance. (Figure page 609)

47. Urinary Buffers
When a person has a blood pH of less than 7.35 (acidosis), the urine pH almost always falls below 5.5.
The nephron cannot produce a urine pH that is significantly less that 4.5.
In order for more H+ to be excreted, the acid must be buffered.
In normal urine, most of H+ excreted is in a buffered form.
Bicarbonate cannot serve this buffering function because it is normally completely reabsorbed.
Instead, the buffering reactions of phosphate (HPO42- )and ammonia (NH3) provide the means for excreting most of the H+ in the urine.
Phosphate enters the urine by filtration.
Ammonia, which is evident in urine from its odor, is produced in the tubule cells by deamination of the amino acid glutamine.
NH H+ → NH4+ (ammonium ion)
HPO H+ → H2PO42-

48. Clinical Applications
The importance of renal function in maintaining homeostasis, and the ease with which urine can be collected and used as a mirror of the plasma’s chemical composition, make the clinical study of renal function and urine composition particularly useful. Further, the ability of the kidneys to regulate blood volume is exploited clinically in the management of high blood pressure.
Use of Diuretics (Table 17.8 page 611)
Diuretics are medications that:
Increase the volume of urine excreted.
Directly lower blood volume and blood pressure.
Act by increasing the proportion of the glomerular filtrate that is excreted as urine.
Decrease the interstitial fluid volume by a more indirect route (by lowering plasma volume and increasing the concentration and the oncotic pressure of the plasma within blood capillaries, this promotes the osmosis of interstitial fluid into the capillary blood helping to reduce the edema).
Are used by people who need to lower their blood volume because of hypertension, congestive heart failure, or edema.

50. Table 17.8 Actions of Different Classes of Diuretics
Category of Diuretic
Mechanism of Action
Loop diuretic
Inhibits Na+ transport
Thiazides
Carbonic anhydrase inhibitors
Inhibits reabsorption of bicarbonate
Osmotic diuretics
Reduces osmotic reabsorption of water by reducing osmotic gradient
Potassium-sparing diuretics
Inhibits action of aldosterone OR
Inhibits Na+ reabsorption and K+ secretion

52. Renal Function Tests and Kidney Disease
Some techniques used to test renal function are:
Measurement of the renal plasma clearance of PAH (para-aminohippuric acid), which measures total blood flow to the kidneys.
Measurement of the GFR by the inulin clearance.
Measurement of the plasma creatinine concentration provides an index of renal function.
Measurement of the urinary albumin excretion rate detect an excretion rate of blood albumin that is slightly above normal; a condition called microalbuminuria ( mg protein/day) which is often the first manifestation of renal damage that may be caused by diabetes or hypertension.
Proteinuria is present when a person excretes more than 300 mg of
protein/day.
Nephrotic syndrome if the excretion is greater than 3.5 g/day.

53. Acute Renal Failure
The ability of the kidneys to function properly deteriorates over a relatively short period of time (hours to days).
Indications are: 1. A rise in blood creatinine concentration.
2. A decrease in renal plasma clearance of creatinine.
This may be due to a reduced blood flow through the kidneys.
Reduced blood flow(ischemia) may resulted from:
1. Atherosclerosis.
2. Inflammation of the renal tubules.
3. Excessive use of certain drugs including nonsteroidal anti-inflammatory
drugs.

54. Glomerulonephritis
Inflammation of the glomeruli.
Believed to be an autoimmune disease (involves the person's own antibodies).
Antibodies appear to have been produced in response of streptococcus infections (such as strep throat).
These antibodies may have been raised against the basement membrane of the glomerular capillaries.
As a result, a variable number of glomeruli are destroyed, and the remaining glomeruli become more permeable to plasma proteins. Leakage of proteins into the urine results in decreased plasma colloid osmotic pressure and can lead to edema.

55. Renal Insufficiency
Develops when nephrons are destroyed.
Renal insufficiency results from:
Chronic glomerulonephritis.
Pyelonephritis (infection of the renal pelvis and nephrons).
Loss of a kidney.
Reduction of kidney function caused by:
a. Diabetes mellitus.
b. Arteriosclerosis.
c. Blockage by kidney stones.

56. Consequences of renal insufficiency are:
Hypertension: due primarily to the retention of salt and water.
Uremia: high plasma urea concentrations accompanied by acidosis, and an elevated K+ concentration (which are more immediately dangerous than the high levels of urea) leading to uremic coma.
Patients with renal insufficiency are often placed on a dialysis machine (artificial kidney for hemodialysis).
Hemodialysis is commonly performed 3 times/week for several hours each session.
More recent techniques include the use of the patient’s own peritoneal membranes for dialysis, called continuous ambulatory peritoneal dialysis (CAPD). This type can be performed several times a day by the patients themselves on an outpatient basis.
Although CAPD is more convenient and less expensive for patients than hemodialysis, it is less efficient in removing wastes and it is more often complicated by infection.

57. The ability of the kidneys to regulate blood volume and chemical composition in accordance with the body’s changing needs requires great complexity of function.
Homeostasis is maintained in the body by coordination of renal functions with those of the cardiovascular and pulmonary systems.

59. The Renin-Angiotensin-Aldosterone System

60. Maintaining Acid-Base Balance