I.

Anatomy and Histology of the Kidneys

A. EXTERNAL ANATOMY

B. INTERNAL ANATOMY
1. Renal cortex  
 a superficial, light red region of kidney
 the smooth-textured area extending from the renal capsule to the bases of the renal
pyramids and into the spaces between them.  
2. Renal medulla  
 a deep, darker reddish-brown inner region  
 consists of several cone-shaped renal pyramids  
3. Renal papilla  
 The base (wider end) of each pyramid faces the renal cortex, and its apex (narrower
end), points toward the renal hilum.  
4. renal columns  
 portions of the renal cortex that extend between renal pyramids  
5. Parenchyma  
 functional portion of the kidney. That the renal cortex and renal pyramids of the renal
medulla constitute.  
6. Nephrons  
 Within the parenchyma are the functional units of the kidney—about 1 million
microscopic structures  
7. papillary ducts  
 drain into cuplike structures called minor and major calyces  
8. renal pelvis   
 From the major calyces, urine drains into a single large cavity and then out through the
ureter to the urinary bladder.      
9. renal sinus 
 The hilum expands into a cavity within the kidney. which contains part of the renal
pelvis, the calyces, and branches of the renal blood vessels and nerves. 

C. BLOOD AND NERVE SUPPLY

1. renal arteries
the kidneys constitute less than 0.5% of total body mass, they receive 20–25% of the resting
cardiac output via the right and left renal arteries
2. renal blood flow
the blood flow through both kidneys, is about 1200 mL per minute
3. segmental arteries
which supply diff erent segments (areas) of the kidney
4. interlobar arteries
enter the parenchyma and pass through the renal columns between the renal lobes
5. renal lobe
consists of a renal pyramid, some of the renal column on either side of the renal pyramid, and
the renal cortex at the base of the renal pyramid
6. arcuate arteries
the bases of the renal pyramids, the interlobar arteries arch between the renal medulla and
cortex
7. cortical radiate arteries
Divisions of the arcuate arteries produce a series of cortical radiate arteries
aff erent arterioles
These arteries radiate outward and enter the renal cortex. they give off branches
8. Glomerulus
Each nephron receives one aff erent arteriole, which divides into a tangled, ball-shaped
capillary network
9. Efferent arteriole
that carries blood out of the glomerulus
 efferent arterioles divide to form the peritubular capillaries,which surround tubular parts of
the nephron in the renal cortex
10. vasa recta
long, loop-shaped capillaries, supply tubular portions of the nephron in the renal medulla
cortical radiate veins
receive blood from the vasa recta.
The blood drains through the arcuate veins to the interlobar veins running between the renal
pyramids
11. renal vein
exits at the renal hilum and carries venous blood to the inferior vena cava.
D. NEPHRON
Parts of a Nephron
consists of two parts:

renal corpuscle, where blood plasma is filtered

Two components of a renal corpuscle
Glomerulus (capillary network) and the glomerular capsule
a double-walled epithelial cup that surrounds the glomerular capillaries. Blood plasma
is filtered in the glomerular capsule, and then the filtered fluid passes into the renal tubule,
which has three main sections

renal tubule into which the filtered fluid passes

The renal tubule consists

(1) proximal convoluted tubule (PCT)
Proximal denotes the part of the tubule attached to the glomerular capsule, and distal
denotes the part that is further away. Convoluted means the tubule is tightly coiled rather
than straight

(2) nephron loop

the nephron loop extends into the renal medulla, makes a hairpin turn, and then
returns to the renal cortex.
connects the proximal and distal convoluted tubules
descending limb of the nephron loop
The first part of the nephron loop begins at the point where the
proximal convoluted tubule takes its final turn downward. begins in the renal
cortex and extends downward into the renal medulla

ascending limb of the nephron loop.

makes that hairpin turn and returns to the renal cortex where it
terminates at the distal convoluted tubule. About 80–85% of the nephrons are
cortical nephrons

juxtamedullary nephrons
have a long nephron loop that extends into the deepest region of the
medulla
the ascending limb of the nephron loop of juxtamedullary nephrons consists
of two portions: a thin ascending limb followed by a thick ascending limb

(3) distal convoluted tubule (DCT).

The distal convoluted tubules of several nephrons empty into a single collecting
duct (CD) Collecting ducts then unite and converge into several hundred large papillary
ducts, which drain into the minor calyces.

Histology of the Nephron and Collecting Duct

 A single layer of epithelial cells forms the entire wall of the glomerular capsule, renal tubule,
and ducts. However, each part has distinctive histological features that reflect its particular
functions.

Glomerular Capsule
The glomerular (Bowman’s) capsule consists of visceral and parietal layers.
The visceral layer consists of modified simple squamous epithelial cells called podocytes footlike
projections of these cells (pedicels) wrap around the single layer of endothelial cells of the
glomerular capillaries and form the inner wall of the capsule.

Renal Tubule and Collecting Duct

form the renal tubule and collecting duct. In the proximal convoluted tubule, the cells are
simple cuboidal epithelial cells with a prominent brush border of microvilli on their apical surface
(surface facing the lumen). These microvilli, like those of the small intestine, increase the surface
area for reabsorption and secretion.

Renal Physiology
To produce urine, nephrons and collecting ducts perform three basic processes—glomerular filtration,
tubular reabsorption, and tubular secretion

1.Glomerular filtration.
the first step of urine production, water and most solutes in blood plasma move across the
wall of glomerular capillaries, where they are filtered and move into the glomerular capsule and then
into the renal tubule.
2 Tubular reabsorption.
As filtered fluid flows through the renal tubules and through the collecting ducts, tubule cells
reabsorb about 99% of the filtered water and many useful solutes.
The water and solutes return to the blood as it flows through the peritubular capillaries and
vasa recta. Note that the term reabsorption refers to the return of substances to the bloodstream. The
term absorption, by contrast, means entry of new substances into the body, as occurs in the
gastrointestinal tract.
3 Tubular secretion.
As filtered fluid flows through the renal tubules and collecting ducts, the renal tubule and duct
cells secrete other materials, such as wastes, drugs, and excess ions, into the fluid. Notice that
tubular secretion removes a substance from the blood

Glomerular Filtration
The fluid that enters the capsular space is called the glomerular filtrate. The fraction of
blood plasma in the aff erent arterioles of the kidneys that becomes glomerular filtrate is the filtration
fraction.

The Filtration Membrane

Substances filtered from the blood cross three filtration barriers—a glomerular endothelial cell, the
basement membrane, and a filtration slit formed by a podocyte

Glomerular endothelial cells

are quite leaky because they have large fenestrations that measure 0.07– 0.1 𝜇m in diameter.
Located among the glomerular capillaries and in the cleft between aff erent and eff erent arterioles
are mesangial cells. These contractile cells help regulate glomerular filtration.
basement membrane
a layer of acellular material between the endothelium and the podocytes, consists of minute
collagen fibers and negatively charged glycoproteins. allow water and most small solutes to pass
through.

pedicels
wrap around glomerular capillaries.

Net Filtration Pressure

Glomerular filtration depends on three main pressures. One pressure promotes filtration and two
pressures oppose filtration

Glomerular blood hydrostatic pressure (GBHP)

is the blood pressure in glomerular capillaries.
GBHP is about 55 mmHg.
Capsular hydrostatic pressure (CHP)
is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular
space and renal tubule. CHP is about 15 mmHg.
Blood colloid osmotic pressure (BCOP),
due to the presence of proteins such as albumin, globulins, and fibrinogen in blood plasma, also
opposes filtration. The average BCOP in glomerular capillaries is 30 mmHg

Renal Autoregulation of GFR

help maintain a constant renal blood flow and GFR despite normal, everyday changes in blood
pressure, like those that occur during exercise. and consists of two mechanisms—the myogenic
mechanism and tubuloglomerular feedback.

The myogenic mechanism

occurs when stretching triggers contraction of smooth muscle cells in the walls of aff erent
arterioles
The second contributor to renal autoregulation, tubuloglomerular feedback is so named because
part of the renal tubules—the macula densa—provides feedback to the glomerulus

Neural Regulation of GFR

those of the kidneys are supplied by sympathetic ANS fibers that release norepinephrine.
Norepinephrine causes vasoconstriction through the activation of α1 receptors, which are particularly
plentiful in the smooth muscle fibers of aff erent arterioles.

Hormonal Regulation of GFR

Hormone regulation Angiotensin II

Decreased blood volume or blood pressure stimulates production of angiotensin II.
Atrial natriuretic peptide (ANP)
Stretching of atria of heart stimulates secretion of ANP.

Tubular Reabsorption and Tubular Secretion

Reabsorption Routes
A substance being reabsorbed from the fluid in the tubule lumen can take one of two routes before
entering a peritubular capillary: It can move between adjacent tubule cells or through an individual
tubule cell

The apical membrane (the tops of the soda cans) contacts the tubular fluid,
the basolateral membrane (the bottoms and sides of the soda cans) contacts interstitial fluid at the
base and sides of the cell.

Regulation of Body Temperature

 Your body produces more or less heat depending on the rates of its metabolic reactions.
Because homeostasis of body temperature can be maintained only if the rate of heat loss from
the body equals the rate of heat production by metabolism, it is important to understand the
ways in which heat can be lost, gained, or conserved.
Heat: is a form of energy that can be measured as temperature.
Core temperature: is the temperature in body structures deep to the skin and subcutaneous layer.
Shell temperature: is the temperature near the body surface—in the skin and subcutaneous layer.

Mechanisms of Heat Transfer

 Maintaining normal body temperature depends on the ability to lose heat to the environment at
the same rate as it is produced by metabolic reactions. Heat can be transferred between the
body and its surroundings in four ways: via conduction, convection, radiation, and evaporation.

1. Conduction is the heat exchange that occurs between molecules of two materials that are in direct
contact with each other. At rest, about 3% of body heat is lost via conduction to cooler, solid materi-
als in contact with the body, such as a chair, clothing, and jewelry. Heat can also be gained via
conduction—for example, while soak- ing in a hot tub. Because water conducts heat 20 times more
effec- tively than air, heat loss or heat gain via conduction is much greater when the body is
submerged in cold or hot water.
2. Convection is the transfer of heat by the movement of air or wa- ter between areas of different
temperatures.
3. Radiation is the transfer of heat in the form of infrared rays be- tween a warmer object and a
cooler one without physical con- tact.
4. Evaporation is the conversion of a liquid to a vapor. Every milli- liter of evaporating water takes
with it a great deal of heat.

Hypothalamic Thermostat
 The control center that functions as the body’s thermostat is a group of neurons in the anterior
part of the hypothalamus, the preoptic area.
 Neurons of the preoptic area generate action potentials at a higher frequency when blood
temperature increases and at a lower frequency when blood temperature decreases.
 Action potentials from the preoptic area propagate to two other parts of the hypothalamus
known as the heat-losing center and the heat-promoting center, which, when stimulated by
the preoptic area, set into operation a series of responses that lower body tem- perature and
raise body temperature, respectively.

Thermoregulation
Vasoconstriction: Action potentials from the heat-promoting center stimulate sympathetic nerves
that cause blood vessels of the skin to constrict. Vasoconstriction decreases the flow of warm blood,
and thus the transfer of heat, from the internal organs to the skin. Slowing the rate of heat loss allows
the internal body temperature to in- crease as metabolic reactions continue to produce heat.
Release of epinephrine and norepinephrinel: Action potentials in sympathetic nerves leading to
the adrenal medulla stimulate the release of epinephrine and norepinephrine into the blood. The
hormones in turn bring about an increase in cellular metabolism, which increases heat production.

Shivering: The heat-promoting center stimulates parts of the brain that increase muscle tone and
hence heat production.
Release of thyroid hormones: The thyroid gland responds to TSH by releasing more thyroid
hormones into the blood. As increased levels of thyroid hormones slowly increase the metabolic rate,
body tem- perature rises.

Nutrients
 Nutrients are chemical substances in food that body cells use for growth, maintenance, and
repair. The six main types of nutrients are water, carbohydrates, lipids, proteins, minerals, and
vitamins.
 Water is the nutrient needed in the largest amount about 2–3 liters per day. As the most
abundant compound in the body, water provides the medium in which most metabolic
reactions occur, and it also participates in some reactions.

Minerals
 Minerals are inorganic elements that occur naturally in the earth’s crust. In the body they
appear in combination with one another, in combination with organic compounds, or as ions in
solution.
 Minerals constitute about 4% of total body mass and are concentrated most heavily in the
skeleton. Minerals with known functions in the body include calcium, phosphorus, potassium,
sulfur, sodium, chloride, magnesium, iron, iodide, manganese, copper, cobalt, zinc, fluoride,
selenium, and chromium.
 Excess amounts of most minerals are excreted in the urine and feces.

Vitamins
 Organic nutrients required in small amounts to maintain growth and normal metabolism are
called vitamins.
 Unlike carbohydrates, lipids, or proteins, vitamins do not provide energy or serve as the body’s
building materials. Most vitamins with known functions are coenzymes.
 The body can assemble some vitamins if the raw materials, called provitamins, are provided.
 The fat-soluble vitamins, vitamins A, D, E, and K, are absorbed along with other dietary lipids
in the small intestine and packaged into chylomicrons.

Disorders: Homeostatic Imbalances

Anorexia Nervosa
 Anorexia nervosa is a chronic disorder characterized by self-induced weight loss, negative
perception of body image, and physiological changes that result from nutritional depletion.
 Patients with anorexia nervosa have a fixation on weight control and often insist on having a
bowel movement every day despite inadequate food intake.
 They often abuse laxatives, which worsens the fluid and electrolyte imbalances and nutrient
deficiencies.
 The disorder is found predominantly in young, single females, and it may be inherited. Fever

Fever
 A fever is an elevation of core temperature caused by a resetting of the hypothalamic
thermostat. The most common causes of fever are viral or bacterial infections and bacterial
toxins; other causes are ovulation, excessive secretion of thyroid hormones, tumors, and
reactions to vaccines. When phagocytes ingest certain bacteria, they are stimulated to secrete
a pyrogen.

Obesity
 Obesity is body weight more than 20% above a desirable standard due to an excessive
accumulation of adipose tissue. More than one-third of the adult population in the United
States is obese.
Anatomy of the Kidneys
 The paired kidneys are reddish, kidney bean–shaped organs located just above the waist
between the peritoneum and the posterior wall of the abdomen. Because their position is
posterior to the peritoneum of the abdominal cavity, the organs are said to be retroperitoneal.
 The kidneys are located between the levels of the last thoracic and third lumbar vertebrae, a
position where they are partially protected by ribs 11 and 12.
 If these lower ribs are fractured, they can puncture the kidneys and cause significant, even life-
threatening damage. The right kidney is slightly lower than the left because the liver occupies
considerable space on the right side superior to the kidney.

External Anatomy of the Kidneys

 A typical adult kidney is 10–12 cm (4–5 in.) long, 5–7 cm (2–3 in.) wide, and 3 cm (1 in.) thick
about the size of a bar of bath soap—and has a mass of 135–150 g (4.5–5 oz.).
 The concave medial border of each kidney faces the vertebral column. Near the center of the
concave border is an indentation called the renal hilum through which the ureter emerges from
the kidney along with blood vessels, lymphatic vessels, and nerves.
Paracellular reabsorption

fluid that leak between the cells in a passive process.

Transcellular reabsorption substance passes from the fluid in the tubular lumen through the apical membrane of a
tubule cell, across the cytosol, and out into interstitial fluid through the basolateral membrane.

TRANSPORT MECHANISMS

When renal cells transport solutes out of or into tubular fluid, they move specific substances in one direction only. Not
surprisingly, different types of transport proteins are present in the apical and basolateral membranes.

Primary active transport

the energy derived from hydrolysis of ATP is used to “pump” a substance across a membrane; the sodium–potassium
pump is one such pump.

Secondary active transport

the energy stored in an ion’s electrochemical gradient, rather than hydrolysis of ATP, drives another substance across a
membrane.

Symporters

are membrane proteins that move to or more substances in the same direction across a membrane.

Antiporters

move two or more substances in oppositedirections across a membrane.

Transport limit each type of transporter has an upper limit on how fast it can work, it measured in mg/min.

Obligatory water reabsorption

water reabsorbed with solutes in tubular fluid fluids.

Facultative water reabsorption

it called when reabsorption of the final 10% of the water, a total of 10-20 liters per day. Facultive means “capable of
adapting to a need.”

Glucosuria

when the blood concentration of glucose is above 200mg/ml , the renal symporters cannot work fast enough to
reabsorb all the glucose enters the glomerular filtrate. Some glucose remains in the urine, a condition called glucosuria.
The most common cause of glucosuria is diabetes mellitus.

Urine is the fluid that drains from papillary ducts into the renal pelvis.

REABSORPTION AND SECRETION IN THE PROXIMAL CONVOLUTED TUBULE

Na+ symporters is located in the apical membrane.

Carbonic anhydrase the enzymes that also occurs in RBC it catalyzes the reaction of CO2 with water to form a carbonic
acid.

Actions of Na+ -H+ antiporters in proximal convoluted tubule cells.

a.) Reabsorption of Sodium ions (Na+) and secretion of hydrogen ions (H+) via secondary active transport through
the apical membrane.
b.) Reabsorption of bicarbonate ions (HCO3-) via facilitated diffusion through the basolateral membrane.

Amonia

is a poisonous water product derived from the deamination of various amino acids, a reaction that occurs mainly in
hepatocytes.

Aging and the urinary system

URINARY TRACT INFECTIONS

The term urinary tract infection (UTI) is used to describe either an infection of a part of the urinary system or the
presence of large num- bers of microbes in urine. UTIs are more common in females due to the shorter length of the
urethra. Symptoms include painful or burn- ing urination, urgent and frequent urination, low back pain, and bed-
wetting. UTIs include urethritis (ū-rē-THRĪ-tis), inflammation of the urethra; cystitis (sis-TĪ-tis), inflammation of the
urinary bladder; and pyelonephritis (pī-e-lō-ne-FRĪ-tis), inflammation of the kidneys. If pye- lonephritis becomes chronic,
scar tissue can form in the kidneys and severely impair their function. Drinking cranberry juice can prevent the
attachment of E. coli bacteria to the lining of the urinary bladder so that they are more readily flushed away during
urination.

RENAL FAILURE

Renal failure is a decrease or cessation of glomerular filtration. In acute renal failure (ARF), the kidneys abruptly stop
working entirely (or almost entirely). The main feature of ARF is the suppression of urine flow, usually characterized
either by oliguria (ol′-i-GŪ-rē-a), daily urine output between 50 mL and 250 mL, or by anuria (an-Ū- rē-a), daily urine
output less than 50 mL. Causes include low blood volume (for example, due to hemorrhage), decreased cardiac output,
damaged renal tubules, kidney stones, the dyes used to visualize blood vessels in angiograms, nonsteroidal anti-
inflammatory drugs, and some antibiotic drugs(e.g. acyclovir, oseltamivir). It is also common in people who suffer a
devastating illness or overwhelming traumatic injury; in such cases it may be related to a more general organ failure
known as multiple organ dysfunction syndrome (MODS).

Renal failure causes a multitude of problems. There is edema due to salt and water retention and metabolic acidosis due
to an inability of the kidneys to excrete acidic substances. In the blood, urea builds up due to impaired renal excretion of
metabolic waste products and potassium level rises, which can lead to cardiac arrest. Often, there is anemia because the
kidneys no longer produce enough erythropoie- tin for adequate red blood cell production. Because the kidneys are no
longer able to convert vitamin D to calcitriol, which is needed for adequate calcium absorption from the small intestine,
osteomalacia also may occur.

POLYCYSTIC KIDNEY DISEASE

Polycystic kidney disease (PKD) (pol′-ē-SIS-tik) is one of the most common inherited disorders. In PKD, the kidney tubules
become rid- dled with hundreds or thousands of cysts (fluid-filled cavities). In addition, inappropriate apoptosis
(programmed cell death) of cells in noncystic tubules leads to progressive impairment of renal function and eventually to
end-stage renal failure.

People with PKD also may have cysts and apoptosis in the liver, pancreas, spleen, and gonads; increased risk of cerebral
aneurysms; heart valve defects; and diverticula in the colon. Typically, symptoms are not noticed until adulthood, when
patients may have back pain, urinary tract infections, blood in the urine, hypertension, and large abdominal masses.
Using drugs to restore normal blood pressure, re- stricting protein and salt in the diet, and controlling urinary tract in-
fections may slow progression to renal failure. Angiotensin II receptor blockers such as captopril.

URINARY BLADDER CANCER Each year, nearly 12,000 Americans die from urinary bladder cancer. It generally strikes
people over 50 years of age and is three times more likely to develop in males than females. The disease is typically pain-
less as it develops, but in most cases blood in the urine is a primary sign of the disease. Less often, people experience
painful and/or fre- quent urination.

As long as the disease is identified early and treated promptly, the prognosis is favorable. Fortunately, about 75% of
urinary bladder cancers are confined to the epithelium of the urinary bladder and are easily removed by surgery. The
lesions tend to be low-grade, meaning that they have only a small potential for metastasis. Darifenacin(Enablex)

Urinary bladder cancer is frequently the result of a carcinogen. About half of all cases occur in people who smoke or
have at some time smoked cigarettes. The cancer also tends to develop in people who are exposed to chemicals called
aromatic amines. Workers in the leather, dye, rubber, and aluminum industries, as well as painters, are often exposed to
these chemicals.

Cystoscopy (sis-TOS-kō-pē; cysto- = bladder; -scopy = to examine) is a very important procedure for direct examination
of the mucosa of the urethra and urinary bladder and prostate in males. In the procedure, a cystoscope (a flexible
narrow tube with a light) is inserted into the ure- thra to examine the structures through which it passes. With special
attachments, tissue samples can be removed for examination (biopsy) and small stones can be removed. Cystoscopy is
useful for evaluating urinary bladder problems such as cancer and infections. It can also evaluate the degree of
obstruction resulting from an enlarged prostate. (aspirin)