Learning Objectives: Chapter 24, Structure and Function of the Kidney

On completion of the chapter, the reader should be able to:

1. Describe the anatomy and physiology of the structures of the renal system.
Location: bean-shaped organ that lie outside the peritoneal cavity in the back of the upper abdomen, one on
each side of the vertebral column at the level of the 12th thoracic to 3rd lumbar vertaebrae. The right kidney
normally is lower than the left, persumably because of the position of the liver.
o The medial border of the kidney is indented by a dep fissure called the hilus. - here that blood vessels
and nerves enter and leave the kidney. Ureters also enter the kidney at this location.
o Two distinct regions can be identified on the bisected kidney - an outer cortex and an inner medulla.
The cortex (outer part) has a reddish-brownish granular appearance that is absent from the medulla.
The medulla (inner part) consists of light-colored, coned shaped masses.
o The adipose tissue protects the kidney from mechanical blows and assists, together with the attached
blood vessels and fascia, in holding the kidney in place.
Gross function: The Kidneys filter physiologically essential substances, such as NA- and K+, from the blood
and selectively reabsorb those substances that are needed to maintain the normal composition of internal body
fluids.
o Also release renin, an enzymatic hormone that participates in the regulation of blood pressure; Also
produces erythropoietin - a hormone that stimulates red blood cell production; and they convert
vitamin D to its active form
Structure of glomerulus: Blood comes in to the kidney through the afferernt arteriole and forms the
glomerulus and then exits the kidney through the efferent arteriole. Filtrate form here is squeezed out into the
bowmans capsule. Na+, glucose, amino acids may get filtered. However, large proteins, RBC will not get
filtered. The glomerular capilalry cells sit along a basement membrane. Bowman capsule epithelium cells sit
along the same basement membrane.
o Bowman's capsule goes to proximal convoluted tubule (reabsorption of Na, Cl-, HCO3-, K+, H20,
glucose) - (secretion of H+, organic acids and bases) --> loop of henle
o Descending loop of henle: Only permeable to water. Since this are is hypertonic, the water will leave
the descenting loop of henle and go into the medulla, leading to water reabsorption.
o Ascending loop of henle: Pumps out Na+, K+ and Cl-, Ca++, HCO3- and Mg++ into the medulla.
Not permeable to water. Secretion of H+
o Distal convoluted tubule: Reabsorption of Na, Cl-, Ca++, Mg++
o Collecting duct: ADH controls H20 reabsorption
Function of glomerulus: Blood is filtered, and a system of tubular structures where water, electrolytes and
other substances needed to maintain the constancy of the internal enbironment are reabsorbed into the blood
stream while other, unneeded material are secreted into tubular filtration for elimination.
Strucutre of nephrons: Consists of glomerulus. Nephrons are grouped into two categories
o 85% originate in the superficial part of the cortex and are called cortical nephrons - they have short,
thick loops of henle that penetrate only a short distance into the medulla.
o 15% are called juxtamedullary nephron - originate deeper in the cortex and have longer and thinner
loops of henle that panetrate the entire length of the medulla.
Function of nephrons: Capable of producing urine, maintain water and produce hormones
2. Compare and contrast filtration, reabsorption, and secretion.
Glomerular Filtration: Starts with filtration of protein-free plasma through the glomerular capillaries into
bowman space. Filtration rate is determined by capillary filtration pressure, colloidal osmotic pressure and
capillary permeability that affect fluid movement through other capillaries in the body.
o Approximately 125mL is filtrate is formed each minute = glomerular filtration rate.
o Glomerulus is located between two arteries, which is why there is a high pressure filtration system.
o The filtration pressure and the GFR are regulated by relaxation and constriction of the afferent and
efferent arterioles.

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Example1: Relaxation of afferent arterioles = increases filtration pressure and GFR by increasing
glomerular blood flow
Example 2: Relaxation of efferent arteriole decreases resistances to outflow of blood, decreasing
glomerular filtration and GFR
Both innervated by sympathetic nervous system by angiotensin II
During shock there is constriction of afferent arteriole causes a marked decrease in renal blood flow,
and thus decreaseing glomerular filtration pressure.

Tubular Reabsorption and secretion: From bowman's capsule, the glomerular filtrate moves into the tubular
segments of the nephron.
o Mechanism of transport across tubular cell membrane are active and passive transport
o Water and urea are passible absorbed along concentration gradients
o Sodium and other electrolytes, as well as urate, glucosea and amino acids are reabsorbed using
primary or secondary active transport.
o Under nomral conditions 1mL of the 125mL of the glomerular flitrate that is formed each minute is
excreted in the urine. The other 124m: is reabsorbed in the tubules. This means that the average
outpute of urine is approximately 60mL/hour.

3. Describe how the kidney produces a concentrated or dilute urine.

Regulation of urine concentraiton: The ability of the kidney to respond to changes in the osmolality of the
extracellular fluids by producing either a concenrated or dilute urine depends on the establishment of high
concentration of osmotically active patricles in the interstitium of the kidney medulla and the action of the
ADH in regulating the water permeatbility of the surrounding medullary collective tubes.
o 1/5th of the juxtamedullary nephron, the loop of henle and vasa recta descents into the medullary
portion of the kidney, forming a counter-current system that controls water and solute movement so
that water is kept out of the area of the surrounding the tubule and solutes are retained.
o There is an exchange of solute between the adjacent descending and ascending loops of Henle
between the ascending and descending sections of the vasa recta. Because of these exchange process,
a high concentration of osmotically active particles collects in the interstitium of the kidney medulla.
The presence of these osmotically active particles in the interstitium surrounding the medullary
collecting tubules facilitates the ADH-mediated reabsoption of water.
4. Describe the elimination functions of the kidney.
Elimination of sodium and potassium is regulated by the GFR and by homoral agents that control their
reabsorption
Aldosterone, a hormone secreted by the adrenal gland, functions in the reglation of sodium and potassium
elimination by the principal cells int he distal and collecting tubules
Sodium reabsorption in the distal and collecting tubule is highly variable and depends on the presence of
aldosterone

In the presence of aldosterone, which stimulates sodium absorption and simultaneous excretion of
potassium into the tubular fluid, almost all the sodium in the distal tubular fluid is reabsorbed and the
urine essentially becomes sodium free. When no aldosterone, no sodium reabsorbed from the distal
tubule and excessive amounts of sodium are lost in the urine.
Atrial natruretic peptide: It is made by overstretched atria - it causes the kidneys to stop reabosrbing NaCL.
Therefore, NaCl and water are lost in the ruine, reducing blood volume and decreasing the stretch and
workload of the heart. This helps decrease vascular volume by increasing urine output.
Regulation of body pH: Virtually all the excess H+ excreted in the urine is secreted into the tubular fluid by
means of tubular secretory mechanism.
o The ability of the kidneys to excrete large amount of H+ in the urine is accomplished by combining
the excess ions with buffers in the urine. The buffers combine with H+ that is secreted into the tubular
fluid, resulting in the formation of carbon dioxide and water.
Other forms of elimination are uric acid elimination, urea elimination and drug elimination.
o

5. Explain the endocrine functions of the kidney.

The renin-angiotensin-aldosterone mechanism: Short term and long term regulation of BP.
o Renin is synthesized and stored in the juxtaglomerular cellso f the kidney
o Released in response to decrease in renal blood flow as a result of sympathetic nervous system
o It converts angiotensinogen to angiotensin I.
o Angiotensin I - few vasoconstrictor properties - leaves the kidneys and enters cirulation
o Angiotensin-converting enzyme converts it to angiotensin II.
o Angiotensin II is a potent vasoconstrictor - acts directly on kidneys to decrease salt and water
excretion
o Angiotensin II stimulates the secretion of aldosteron by adrenal gland - this is for long term
maintainance - increases the reabsorption of sodium in the distal tubule.
Erythropoietin: regulates the differentiation of RBC in the bone marrow.
o synthesis of this is stimulated by tissue hypoxia, which may be brought about by anemia, residence at
high altitudes, or impaired oxygenation of tissue due to cardiac or pulmonary disease
o Person with chronic kidney disease often are anemia because of inability of the kidneys to produce
erythropoietin
Vitamin D: Activation of vit D occurs in the kidneys.
o Increases calcium absorption from the GI tract and helps to regulate calcium deposition in bone.
o Also weak stimulatory effect on renal calcium absorption
o Person with end-stage renal disesae are unable to transform vitamin D to its active form and may
require pharmacologic preparation of the active vitamin for maintaining mineralization of their bones.
6. Select tests of renal functions based on symptoms.
a) Blood and urine test: As renal function declines, there is an increase in serum levels of substances such as urea,
creatinine, phosphate and postassium.
b) Renal Clearance and glomerular filtration rate: Both provide information about the kidney's ability to filter and
reabsorb and/or secrete substances into the blood
Renal clearance measures the rate at which a substance is excreted into the urine.
o one way of estimating the clearacne rate of endogenous creatinine is by collecting timed samples of blood
and urine.
o Creatinine is a product of creatinine metabolism in muscles; its formation and release are relatively
constant and proportional to the amount of the muscle mass present. Because creatinine is freely filtered
in the glomeruli but not reabsorbed from the tubules into the blood nor significantly secreted into the the
tubules from the blood, its blood and urine levels can be used to calculate the GFR.
GFR measures the volume of plasma that is filtered each minute
c) Blood tests: provide valuable information about the kidney's ability to remove metabolic wastes from the blood and
maintain normal electrolyte and pH composition of the blood

Serum creatinine: reflect the GFR.

o Normal values = 0.7mg/DL of blood for a woman with a small frame
o 1.0 mg/DL for a normal adult man
o 1.5 mg/DL for a muscular man
o There is an age-related decline in creatinine clearance in many elderly person becasue muscle mass and
GFR decline with age.
o If value doubles, the GFR and renal function - probably has fallen to one half of its normal state.
o A rise in serum creatinine level to 3x its normal value suggests that there is 75% loss of renal function,
and with creatinine values of 10 mg/DL or more, it can be asssumed that 90% of renal function has been
lost.
Blood Urea nitrogen: Urea is formed in the liver as a by-product of protein metabolism and eliminated entirely by
the kidneys.
o Influenced by protein intake, GI bleeding and hydration status.
o In GI bleeding: the blood is broken down by the intestinal flora, and the nitrogenous waste is absorbed
into the portal vein and transported to the liver, where it is converted to urea
o During dehydration, elevated BUN levels results from increased concentration.
o Approximately 2/3 of renal function must be lost before significant rise in the BUN level occurs.
o BUN is less specific for renal insufficiency than creatinine, but the BUN-creatinine ratio may provide
usefull diagnostic information.
Normally: 10:1
> 15:1 represents prerenal conditions, such as CGF and upper GI tract bleeding, that produces an
increas in BUN but not creatinine.
< 10:1 occurs in person with liver disease and in those who reieve a low-protein diet or chronic
dialysis.
Urine Tests: Kidneys normally produce 1.5L of urine each day. A freshly voided spcimen is most reliable.
o Proteinuria: excessive protein excretion in the urine.
o Urine tests for proteinuria are used to detect abnormal filtering of albumin in the glomeruli or detect in its
reabsoprtion in the renal tubules.
o Protein reagent dipstick can be used as a rapid screening test for the presence of proteins in the urine.
o The microalbuminuria dipstick method only indicates an increase in urinary albumin that is below the
detectable range of the standard proteinuria test. It does not specify the amount of albumin present in the
urine.
Specific gravity and osmolality: measure of concentration of solutes.
o Provides a valuable index of the hydration status and functional ability of the kidneys.
o Normal range = 1.010 to 1.025.
o Healthy kidneys can produce concentrated urine with a specific gravity of 1.030 to 1.040 during periods
of dehydration
o and dilute urine with a concentration that approaches 1.000 during periods of taking too much fluids.
o With diminished renal function, there is a loss of renal concentrating ability and the urine specific gravity
may fall to levels of 1.004 to 1.010 - this is significant during decrease in water intake.
o Urine osmolality depends on the # of particles of solute in a unit of solution.
o More information can be obtained when obtaining serum: urine osmolality. Normal values = 3:1
o A high urine to serum ratio is seen in concentrated urine. With poor concentrating ability, the ratio is low.

Learning Objetives: Chapter 25, Disorders of Renal Function

1. Differentiate disorders of kidney development.
Disorders of kidney development are Agenesis, Hypoplasia, and Dysplasia. In addition, alterations in kidney
position and form can also occur.
Renal Agenesis: complete failure of an organ to develop. Agenesis of both kidneys is incompatible with life.
Newborns with renal agenesis have characteristic fail features - Potter syndrome- fetal compression due to
reduction in amniotic fluid levels (oligohydamnios). Potter syndrome leads to a life threatening conditioning
called pulmonary hypoplasia- caused by inadequate stimulation from the amniotic fluid and compression of the
chest wall.
Renal Hypoplasia: kidneys are small and have less than the normal number of calyces and nephrons. May
effect one or both kidneys. If both kidneys affected then leads to renal failure. History of polyuria and
polydipsia is common.
RenalDysplasia:maldifferentiatedprimitivestructuresprimarilyoftherenaltubules.Theconditionmayeffect
alloronlypartofkidney.Ifentirekidneyisaffecteditscalledmulticysticdysplastickidneydisorderifboth
kidneysaffecteditmaycauseoligohydamnios (low amniotic fluid) and potter syndrome and as a result are
incompatible with life.
Alterations in kidney position and form: the kidneys can develop in an abnormal location; above the pelvic
rim or within the pelvis. One most common alteration is called horseshoe kidney- upper and lower poles of the
two kidneys are fused. But most usually fused at the lower poles which does not cause problems because the
collecting system develops normally and as a result the ureters enter the bladder.
2. Describe the genetic basis for renal cystic disease, the pathology of the disorder, and its signs and
symptoms.
Renal cysts are epithelium lined cavities filled with fluid or semisolid material. The cysts may be single or
multiple and can be symptomatic or asymptomatic. Mostly are single gene disorders and are inherited as
mendelian traits. These include autosomal dominant polycystic kidney disease,autosomal recessive polycystic
kidney disease, and nephronophthisis and medullary cystic kidney diseases.
Autosomal dominant polycystic kidney disease: most common of all inherited kidney diseases. The disorder
is characterized by multiple expanding cysts of both kidneys that ultimately destroy the surrounding kidney
structures and cause renal failure. This disorder has two genetic forms: polycystic 1 caused by mutations in the
PKD1 gene (85% of cases) and polycystic 2 which is caused by mutation in the PKD2 gene (15% of remaining
cases). Symptoms of ADPKD include pain from the enlargement of cysts, hematuria, UTIs, and hypertension
resulting from compression of internal blood vessels which activates the renin-angiotensin mechanism.
Autosomal recessive polycystic kidney disease: cystic dilation of the cortical and medullary collecting
tubules. Caused by mutations in the PKHD1 gene. Serious manifestation present at birth - leads to renal failure
quickly. The infant presents bilateral flank masses accompanied by severe renal failure, impaired lung
development, liver fibrosis, and portal hypertension. Potter syndrome and other defects associated with
oligohydramnios may be present - pulmonary hypoplasia.
Nephronophthisis and medullary cystic kidney diseases:
Nephronophthisis and adult-onset medullary cystic disease both result in progressive medullary
tubulointerstitial cystic disease. Nephronophthisis has a autosomal recessive pattern of inheritance with onset in
infancy, childhood or adolescence. While medullary cystic kidney disease has an autosomal dominant pattern of
inheritance with onset in adolescence and leads to renal failure in adulthood. Both conditions result in small and

shrunken kidneys and presence of a variable number of cysts usually concentrated at the corticomedullary
junction area of the kidney.
3. Differentiate mechanism involved in glomerular injury.
The agents or events that cause glomerular injury include infectious microorganisms, immunologic
mechanisms, drugs, and environmental agents. Most causes of glomerular injury are of immune origin. Two
immune mechanism have been implicated in the development of glomerular disease - (1) antibodies react with
fixed glomerular antigens or (2) circulating antigen-antibody complexes that get trapped in the glomerular
membrane.
Proliferative: hypercellular inflammatory process with proliferation of glomerular cells
Membranous: abnormal thickening of the glomerular basement membrane
Sclerotic: an increase in the amount of extracellular material in the mesangial, sub endothelial, or sub epithelial
tissue of the glomerulus.
4. Differentiate glomerular diseases.
Types of glomerular disease:
Acute nephritic syndrome: acute inflammatory process that occlude the the glomerular capillary lumen and
damages the capillary wall.
Rapidly progressive glomerulonephritis: is a clinical syndrome characterized by severe glomerular injury that
does not have a specific cause. Rapidly progresses within months. It involves focal and segmental proliferation
of glomerular cell and recruitment of monocytes and macrophages with the formation of crescent structures that
obliterate the Bowman space.
Nephrotic Syndrome: characterized by massive proteinuria and lipiduria, and hypoalmuminemia, generalized
edema, and hyperlipidemia. Its not a specific disease but a collection of clinical findings that result from an
increase in glomerular permeability and loss of plasma proteins in the urine. Generalized edema is a hallmark of
nephrotic syndrome and occurs due to loss of albumin which results in decreased colloidal osmotic pressure.
Hyperlipidemia occurs due to increased synthesis of lipoproteins in the liver secondary to a compensatory
increase in albumin production.
Ig A nephropathy: primary glomerulonephritis characterized by the presence if glomerular IgA immune
complex deposits.
Hereditary Nephritis (Alport Syndorme): hereditary defect of the glomerular basement that results in
hematuria and may progress to chronic renal failure.
5. Differentiate tubular and interstitial kidney disorders.
These disorders include acute tubular necrosis, tubulointerstitial nephritis, acute and chronic pyelonephritis,
reflux nephropathy, and nephropathy induced by drugs and toxins.
Tubulointerstitial nephritis: acute or chronic inflammation of the renal tubules and surrounding interstitium.
In chronic tubulointerstitial nephritis there is infiltration with mononuclear leukocytes, interstitial fibrosis, and
widespread tubular atrophy. The tubulointerstitial disorders are distinguished clinically from glomerular
diseases by the absence, in the early stages, of such hallmarks of nephritis and nephrosis as hematuria and
proteinuria, and by the presence of disorders in tubular function.

Pyelonephritis: is a renal disease affecting the tubules, interstitium, and pelvis of the kidney. Acute
pyelonephritis is caused by bacterial infection; whereas chronic pyelonephritis is a more complex disorder
involving not only bacterial infection but other factors such as reflux. In the chronic condition there is scarring
and deformation of the renal calyces and pelvis, along with atrophy and thinning of the over- lying cortex.
Drug-related nephropathies: involve functional or structural changes in the kidneys that occur after exposure
to a drug. Renal tubular cells, particularly proximal tubule cells, are vulnerable to the toxic effects of drugs
because their role in concentrating and reabsorbing glomerular filtrate exposes them to high levels of circulating
toxins. Drugs and other toxic substances can damage the kidneys by causing a decrease in renal blood flow,
directly damaging tubulointerstitial structures, producing hyper-sensitivity reactions, or obstructing urine flow.
Prostaglandins are potent renal vasodilators that contribute to the regulation of renal blood flow. The deleterious
effects of aspirin and other NSAIDs are thought to result from their ability to decrease prostaglandin synthesis
and thus decrease renal blood flow.
6. Differentiate obstructive kidney disorders.
Urinary obstruction can occur in persons of any age and can involve any level of the urinary tract, from the
urethra to the renal pelvis. The conditions that cause urinary tract obstruction include congenital anomalies,
urinary calculi (i.e., stones), pregnancy, benign prostatic hyperplasia, scar tissue resulting from infection and
inflammation, tumors, and neurologic disorders such as spinal cord injury. Lower urinary tract obstructions are
located below the ureterovesical junction and are bilateral in nature. Upper urinary tract obstructions are located
above the ureterovesical junction and are usually unilateral.
The two most damaging effects of urinary obstruction are stasis of urine, which predisposes to infection and
stone formation, and progressive dilation of the renal collecting ducts and renal tubular structures, which causes
destruction and atrophy of renal tissue. The impediment to the outflow of urine causes dilation of the renal
pelvis and calyces associated with progressive atrophy of the kidney.
Hydronephrosisrefers to urine filled dilation of the renal pelvis and calyces associated with progressive
atrophy of the kidney due to obstruction of urine out flow. When the obstruction affects the out ow of urine
from the distal ureter, the increased pressure dilates the ureter, a condition called hydroureter.Urinary tract
obstruction encourages the growth of microorganisms and should be suspected in persons with recurrent urinary
tract infections.
7. Differentiate kidney stones.
The most common cause of upper urinary tract obstruction is urinary calculi. Although stones can form in any
part of the urinary tract, most develop in the kidneys. Kidney stones, also known as nephrolithiasisor renal
calculi, are the third most common disorder of the urinary tract, exceeded only by urinary tract infections and
prostate disorders. kidney stones tend to form in only one kidney. Two factors implicated in kidney stone
formation are a supersaturated urine and an environment that allows the stone to grow.
There are four basic types of kidney stones: calcium (i.e., oxalate or phosphate), magnesium ammonium
phosphate, uric acid, and cystine stones. Calcium stones usually are associated with increased concentrations of
calcium in the blood and urine. Excessive bone resorption caused by immobility, bone disease,
hyperparathyroidism, and renal tubular acidosis all are contributing conditions. Magnesium ammonium
phosphate stones, also called struvitestones,form only in alkaline urine and in the presence of bacteria that
possess an enzyme called urease,which splits the urea in the urine into ammonia and carbon dioxide. Uric acid
stones develop in conditions of gout and high concentrations of uric acid in the urine.
8. Differentiate two major groups of malignant kidney tumors.
There are two major groups of malignant tumors of the kidney: embryonic kidney tumors (i.e., Wilms tumor),
which occur during childhood, and renal cell carcinoma, which occurs in adults. Wilms tumor is one of the most

common malignant tumors of children.The most common presenting signs are a large abdominal mass and
hypertension.Treatment methods include surgery, chemotherapy, and sometimes radiation therapy, with longterm survival rates of up to 96% with an aggressive plan of treatment.
Cancer of the kidney accounts for about 3% of all cancers, with renal cell carcinom a accounting for 80% to
90% of cases.The neoplasms are a collection of tumors from different parts of the nephron, each with different
genetic profiles and histologic features that challenge both diagnostic and treatment methods. Many of these
cancers are characterized by a lack of early warning signs, diverse clinical manifestations, and resistance to
chemotherapy and radiation therapy