Chapter 14
Lecture Outline*
The Kidneys and Regulation of
Water and Inorganic Ions
Eric P. Widmaier
Boston University
Hershel Raff
Medical College of Wisconsin
Kevin T. Strang
University of Wisconsin - Madison
*See PowerPoint Image Slides for all
figures and tables pre-inserted into
PowerPoint without notes.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1
Renal Functions
2
Structure of the Urinary System
Fig. 14-1
3
Functions of the Components of the
Urinary System
• Ureters: transport urine from kidneys to bladder
• Bladder: store urine until voided from body
• Urethra: carry urine from bladder to the outside of
the body
4
Structure of the Kidneys
Fig. 14-4
5
Nephron
• Nephrons are the structural and functional
units of the kidney. Each kidney has over 1
million of these units.
• Each nephron consists of a glomerulus, which
is a tuft of capillaries and a renal tubule.
• The tubule forms a cup shape around the
glomerulus called the glomerular capsule
(Bowman’s capsule).
6
Juxtaglomerular Apparatus
• In the arteriole wall the granular cells (juxtaglomerular cells
(JG)) are enlarged smooth muscle cells that have secretory
granules which contain the hormone renin (part of the reninangiotensin system (RAS).
• The JG cells are mechanoreceptors (they sense blood pressure)
in the afferent arteriole .
• The macula densa is a group of tall, closely-packed cells that are
adjacent to the granular JG cells.
• The macula densa cells are chemoreceptors that respond to
changes in the NaCl content of the filtrate.
• These cells work in tandem and are critical regulators of blood
pressure.
7
Glomerulus
• The capillaries of the glomerulus are fenestrated, which allows
large amounts of solute-rich fluid to pass. REMEMBER THERE
SHOULD NOT BE HIGH AMOUNTS OF PROTEIN IN THE
URINE!
• The inner layer of the glomerular capsule contains highly
modified branching epithelial cells called podocytes.
• Podocytes terminate in foot processes which surround the
basement membrane of the glomerulus. The clefts between the
foot processes are called filtration slits. This is where the filtrate
enters the capsular space.
• The glomerulus also contains a smooth muscle-like cell called a
glomerular mesangial cell. These cells helps regulate the blood
flow in the glomerulus by contraction and engulf
macromolecules that get hung up during filtration.
8
Cortical vs. Juxtamedullary Nephrons
• Juxtamedullary Nephrons:
–
–
–
–
Long loop of Henle
Involved in the concentration of urine
Found at the border between the cortex and medulla
About 15% of all nephrons are in this catagory
• Cortical Nephrons:
– Most nephrons are in this category
– Short loop of Henle
9
Basic Structure of a Nephron
Fig. 14-2
10
Capillaries Associated with Nephrons
• Nephrons are associated with 2 sets of capillaries:
glomerular and peritubular.
• The glomerular capillaries are specialized for filtration.
These are the only capillaries in the body that are fed and
drained by an arteriole (afferent and efferent).
• This allows the blood pressure in the capillary bed to be
very high and it forces fluid and solute out of the blood into
the glomerular capsule.
• Most of the filtrate is reabsorbed in the renal tubule cells
and returns to the blood through the peritubular capillaries.
11
Basic Renal Processes
Fig. 14-6
12
Glomerular Filtration
• Glomerular filtration is a passive process in which hydrostatic
pressures force the fluids and solute through a membrane.
• The glomeruli in the kidney are a much more efficient filter than
other capillary beds in the body because:
1. Filtration membrane is a large surface area and very permeable to
water and solutes.
2. Glomerular pressure is higher (~55 mm Hg), so they produce
180 L vs. 3-4 formed by other capillary beds.
• During filtration it is important to keep the plasma proteins in the
plasma to maintain osmotic (oncotic) pressure.
• If you see blood cells or protein in the urine (protinuria) then
there is a problem with the filtration membrane (common finding
during diabetes and hypertension that signals that kidney damage
has occurred. If untreated will progress to end stage renal disease
and renal failure).
13
Glomerular Filtration
Fig. 14-3
14
Glomerular Filtration
Fig. 14-8
15
Control of GFR by Vascular Changes
Fig. 14-9
16
Tubular Reabsorption
Tubular reabsorption
begins as soon as filtrate
enters the tubule cells.
Paracellular transport
occurs between cells
(even though they have
tight junctions) and is
seen mainly with ions.
Transport can be active
(requires ATP) or passive
(no ATP).
Fig. 14-10 17
Tubular Reabsorption
This transport
maximum is why
untreated diabetic
patients have
glucose in their
urine.
Fig. 14-11
18
Sodium Reabsorption
• Na+ is the most abundant cation in the filtrate.
• Na+ reabsorption is almost always active
transport.
• The active pumping of Na+ (via Na+/K+
ATPase) generates an electrochemical gradient
that couples to passive entrance of other
substances (glucose, etc.) via co-transporters.
19
Tubular Secretion
• Substances such as hydrogen ion, potassium, and organic
anions move from the peritubular capillaries into the
tubular lumen.
• Tubular secretion is an important mechanism for:
1. Disposing of drugs and drug metabolites
2. Eliminating undesired substances or end products that have
reabsorbed by passive processes (urea and uric acid).
3. Removing excess K+
4. Controlling blood pH
20
Differential Handling in the Kidney
Fig. 14-7
21
Metabolism by the Tubules
• Renal tubule cells can synthesize glucose during
fasting and add it to the blood, and they can
catabolize many organic compounds.
22
Regulation of Membrane Channels
and Transporters
• Regulation of reabsorption and/or secretion of
many substances is achieved by regulating the
activity or concentrations of the appropriate
transport proteins in response to hormones and
paracrine/autocrine factors.
23
“Division of Labor” in the Tubules
• The majority of the reabsorption is accomplished by
the proximal tubule and the loop of Henle.
• Extensive reabsorption by the proximal tubule and
Henle’s loop ensures that the masses of solutes and the
volume of water entering the tubular segments beyond
Henle’s loop are relatively small.
• These distal segments then do the fine-tuning for most
substances, determining the final amounts excreted in
the urine by adjusting their rates of reabsorption and, in
a few cases, secretion.
24
Renal Clearance (RC)
• This is the volume of plasma that is cleared of a substance
in one minute (mL/min).
• RC=UV/P
U=concentration of the substance in the urine (mg/mL)
V=flow rate of urine formation (mL/min)
P=concentration of substance in the plasma (mg/mL)
• We use inulin because it is freely filtered and not
reabsorbed and not secreted. Creatine can be used but is
less accurate. It is freely filtered but also secreted in small
amounts.
25
The Concept of Renal Clearance
Fig. 14-12
26
Micturition
• Urine is formed in the renal tubules (filtrate that is
not reabsorbed) and then travels through the calyxes
(major and minor) until it drains into the renal pelvis.
• Fluid drains from the renal pelvis into the ureter,
which then leads to the urinary bladder.
• The bladder stores urine until it is excreted from the
body by the micturition reflex.
• Micturition is initated by a nervous reflex which
causes the smooth muscle of the bladder walls to
contract and the expel the urine.
27
Micturition
Fig. 14-13
28
Incontinence
• Incontinence is the involuntary release of urine.
• The most common types are stress incontinence (due to sneezing, coughing, or
exercise) and urge incontinence (associated with the desire to urinate).
• Incontinence is more common in women.
• Medications (such as estrogen replacement therapy to improve vaginal tone)
can often relieve stress incontinence. Severe cases may require surgery to
improve vaginal support of the bladder and urethra.
• Any irritation to the bladder or urethra (e.g., with a bacterial infection) can
cause urge incontinence. Urge incontinence can be treated with drugs such as
tolterodine or oxybutin, which antagonize the effects of the parasympathetic
nerves on the detrusor muscle. Because these drugs are anticholinergic, they
can have side effects such as blurred vision, constipation, and increased heart
rate.
29
Total-Body Balance of Sodium and Water
30
Basic Renal Processes for Sodium and Water
• Sodium reabsorption is an active process occurring in all
tubular segments except the descending limb of the loop
of Henle.
• Water reabsorption is by diffusion and is dependent
upon sodium reabsorption.
• Water moves through aquaporin channels. The presence
of these aquaporins varies throughout the tubule
segments. They are highly expressed in the proximal
nephron. They are absent in the collecting ducts unless
Anti-diuretic hormone (ADH) is active.
31
Primary Active Sodium Reabsorption
Fig. 14-14
32
Coupling of Water Reabsorption to Sodium
Reabsorption
Fig. 14-15
33
Aquaporins
Fig. 14-16
34
Concentration of Urine Concentration and
Volume
• The kidneys maintain plasma osmolarity at
300 mOsm.
• They does this by using the “countercurrent
mechanisms.”
• Countercurrent systems in the kidney means that
fluid in one tube flows the opposite way in the
adjoining tube.
35
Why this Method Works
• The descending loop of Henle is relatively
impermeable to solutes and freely permeable
to water.
• The ascending limb is permeable to solutes,
but not water.
• Urea recycling contributes to the medullary
osmotic gradient.
36
Urine Concentration: The
Countercurrent Multiplier System
Fig. 14-18
37
Dilute Urine
• Urine is normally diluted as it moves up
through the ascending limb of the loop of
Henle.
• To secrete dilute urine, the DCT and collecting
duct cells secrete substances and then the
kidney just leaves it alone.
• Osmolarity can be as low as 70 mOsm.
38
Concentrated Urine
• ADH uses cAMP systems to cause the
insertion of aquaporins into the membranes of
the principle cells of the collecting ducts. So
water flows out of the collecting ducts to be
reabsorbed by the body.
• Urine can reach 1200 mOsm.
39
Glomerular Filtration Rate
• The GFR is the volume of filtrate formed each
minute.
• This is affected by the volume of surface
available, filtration membrane permeability and
NFP, blood pressure / blood flow to the
glomerular capillaries.
• GFR is directly proportional to the NFP. In the
absence of regulation, increases in systemic blood
pressure mean increases in GFR.
40
Control of
GFR
Fig. 14-21
41
Control of Sodium
Reabsorption
Fig. 14-22
42
Control of
Sodium
Reabsorption
Fig. 14-23
43
ANP and Sodium Excretion
Fig. 14-24
44
Baroreceptor
Control of
Vasopressin
Secretion
Fig. 14-26
45
Osmoreceptor
Control of
Vasopressin
Secretion
Fig. 14-25
46
Summary
Example
Fig. 14-27
47
Thirst and Salt Appetite
Fig. 14-28
48
Renal Regulation of Potassium
Fig. 14-30 49
Aldosterone and K+ Levels
Fig. 14-31 50
Renal Regulation of Calcium and Phosphate
• Calcium reabsorption is increased by
parathyroid hormone.
• Phosphate reabosrption is decreased by
parathyroid hormone.
51
Summary – Division of Labor
52
Diuretics
• Diuretics are substances that promote the loss of Na+ and water.
• Alcohol inhibits the release of ADH.
• Osmotic diuretics----high glucose loads in urine.
• Loop diuretics (lasix, furosemide) are the most powerful
diuretics because they inhibit the formation of the medullar
gradient.
• Hydrochlorithiazide acts on the distal collecting duct.
• Spironolactone is an aldosterone receptor antagonist. This is
known as a K+ sparing diuretic. It acts because the K+ in the
urine is from aldosterone-driven active tubular secretion into the
late DCT and collecting ducts.
53
Sources of Hydrogen Ion Gain or Loss
54
Buffering of Hydrogen Ions in the Body
• The major extracellular buffer is the
CO2/HCO3- system.
• The major intracellular buffers are phosphate
and proteins.
55
Integration of Homeostatic Controls
• The kidneys and the respiratory system work
together to regulate hydrogen ion
concentrations.
56
Renal Mechanisms
• The kidneys eliminate or replenish hydrogen
ions from the body by altering plasma
bicarbonate concentration.
57
Bicarbonate Handling
Fig. 14-32
58
Addition of New Bicarbonate to the Plasma
Fig. 14-33
Fig. 14-34
59
Renal Responses to Acidosis and Alkalosis
60
Classification of Acidosis and Alkalosis
61
Kidney Disease
• Many diseases affect the kidneys including:
– Bacterial infections
– Hypertension
– Diabetes
• End stage renal disease is one of the leading
causes of death in the world and the leading
cause of needed renal transplants.
62
Clinical Issues
• Infection of the renal pelvis occurs usually by
bacteria and is called pyelitis.
• If it affects the whole kidney it is called
pyelonephritis.
• In severe cases the kidney swells, abscesses form and
the pelvis fills with pus. This can result in irrepairable
damage.
• Antibiotics are used to treat this condition.
63
Clinical Issues
• Abnormally low urine output (less the 50
mL/day) is called anuria.
• This may indicate that glomerular blood
pressure is too low to cause filtration.
• Renal failure and anuria can result from any
situation where the nephrons cease to function,
including acute nephritis, transfusion reactions,
and crush injuries.
64
Hemodialysis, Pertoneal Dialysis, and
Transplantation
Fig. 14-35
65