Unit 10

Front 1

1. Identify the structures of the nephron p1280

Back 1

A. The Nephron - the Basic Functional Unit of the Kidney
1. There are 1,200,000 nephrons per kidney
2. There are three types of nephrons
a. Cortical nephrons - have their glomeruli close to the surface of the cortex and have short loops that only partially enter the medulla
b. Midcortical nephrons - have short or long loops extending into the medulla
c. Juxta (lying next to) medullary nephrons- the glomeruli are still in the cortex but abutt the medulla. They have larger glomeruli and longer loops of Henle which extend varying distances into the medulla. These account for only 1/8 of the number of nephrons even though these nephrons are more involved in the concentrating and diluting of urine than the other nephrons.
3. Each nephron is made up of
a. Glomerulus which is a tuft of capillaries branching off of the afferent arteriole. The glomerular capillary bed is a high pressure area because of the vast blood supply that enters (180L of blood is filtered per 24 hours). The capillaries of the glomerulus are 100 times more permeable than other capillaries. Blood enters the capillary tuft through the afferent arteriole and an ultrafiltrate moves into the Bowman's capsule due to the pressure gradient. The blood than leaves the glomerulus through the efferent arteriole.
b. Bowman's capsule - Singular layer of epithelium that surrounds the glomerulus and receives the filtrate. It connects with the first portion of the proximal tubule into which the filtrate flows.
c. Proximal convoluted tubule - the filtrate flows from the Bowman's capsule into the proximal convoluted tubule where mostreabsorption takes place. The proximal tubules are found in the renal cortex
d. Loop of Henle - the filtrate flows from the proximal convoluted tubule into the loop of Henle. There is a descending limb, the loop, and an ascending limb. The latter part of the ascending limb is considered the thick ascending limb. The loop takes part in the countercurrent mechanism
e. Distal tubule - receives filtrate from the loop of Henle and connects to the collecting duct. The distal tubule is also in the renal cortex.
f. Collecting duct - receives filtrate from the distal tubule. The filtrate than empties into the calyx and then into the renal pelvis and to theureter.
g. Vasa Recta - long capillaries that follow the long loop of Henle into the medulla. Picks up the reabsorbed water and electrolytes.

Front 2

2. Describe the process of glomerular filtration p1288

Back 2

A. Glomerular Filtration
1. The main function of the kidney (nephron) is to get rid of wastes by the production and excretion of urine
2. The glomerular membrane
a. Three layers
1. Capillary endothelium - fenestrated
2. Basement membrane - negatively charged, probably secreted by the epithelial cells
3. Capillary epithelium - podocytes that form filtration slits
b. 100 to 150 times more permeable than other membranes
c. The basement membrane is selective. Keeps large molecules (proteins, WBCs and RBCs) from going into filtrate
d. Freely permeable to water and solutes of small molecular dimension
B. Composition of the Ultrafiltrate - Plasma minus the proteins and blood cells
C. Factors that Affect the Glomerular Filtration Rate (GFR)
1. Blood flow - the most significant
a. Increased blood flow increases hydrostatic pressure thus increasing the glomerular filtration rate
b. Decreased blood flow decreases hydrostatic pressure thus decreasing the glomerular filtration rate
c. Blood flow regulated by
i. The ability of the afferent and efferent arterioles to dilate or constrict to regulate flow, which is regulated by sympathetic stimulation, the renin-angiotensin system, and feedback mechanisms within the kidney
ii. Autoregulation - only slight changes in systemic blood pressure will start renal autoregulation to regulate renal blood flow. With hypertension, the afferent arteriole constricts and the efferent arteriole dilates to regulate flow. With hypotension, the opposite is true. Autoregulation fails when the mean arterial blood pressure (MAP) is below 80 mm Hg and/or above 180mm Hg. An easy way to determine MAP is MAP = (SBP+2xDBP)/3
2. Pressure changes within the Bowman's capsule - Increased pressure within the capsule decreases glomerular filtration
3. Plasma oncotic pressure - The level of plasma proteins. Also, if the flow rate increases, this may push proteins out quickly, decreasingoncotic pressure.

Front 3

3. Differentiate the electrolytes reabsorbed and secreted by the proximal and distal tubules p1291

Back 3

tubular Reabsorption
1. Defined - reabsorption is when a substance moves from the tubular lumen into the interstitium and then into the peritubular capillaries. The transport of these substances are the same as any other place in the body,
1. Simple diffusion related to concentration or electrochemical gradients
2. Osmosis - water follows sodium
3. Active transport using a carrier

Front 4

4. Discuss the principles of the countercurrent mechanism and its significance in the concentration of urine p1293

Back 4

P1293

Front 5

5. Describe the various functions of the kidneys p1288

Back 5

Major function of the nephron is urine formation, which involves the processes of flomerular filtration, tubular reabsoption, and tubular secretion and excretion.

Front 6

6. Identify three ways that blood flow to the kidney is regulated p1285

Back 6

Autoregulation as described above
Neural regulation -
1. Renal arteries innervated by the sympathetic nervous system
2. Renal blood flow also related to systemic blood pressure
Hormonal control
1. ADH from the posterior pituitary
a. Opens the pores along the distal tubule and collecting duct to allow for the reabsorption of water.
b. Responds to hypovolemia and increased serum osmolality
2. Atrial natriuretic factor
a. Secreted by the cells in the atrium in response to atrial stretch
b. Also secreted by the hypothalamus
c. Promotes sodium (and therefore water) excretion by acting on the renal tubules
3. Endothelin
a. Secreted by the endothelial cells of renal vessels, mesangial cells, and distal tubular cells
b. Potent vasoconstrictor of afferent and efferent arterioles
4. Aldosterone
a. Released in response to Renin release by the juxtaglomular apparatus (JGA) of the kidney
b. JGA senses reduced blood flow to the glomerulus and decreased delivery of sodium to the distal nepron. JGA also responds to sympathetic stimulation of the kidneys

Front 7

7. Discuss the clinical significance of blood urea nitrogen and creatinine measurements p1296

Back 7

A. The primary wastes excreted by the kidney include urea, creatinine, uric acid, bilirubin, and metabolic acids ( ammonium chloride and ammonium sulfate)
B. Urea (plasma 8-22 mg/dl)
1. Measured in the blood as the blood urea nitrogen level (BUN) and is the end product of protein metabolism. It results from ammonia breakdown in the liver.
2. Urea levels are influenced by protein metabolism and intake, as well as renal excretion
3. With decreased renal blood flow, the kidneys increase reabsorption of urea thus increasing plasma urea concentration
4. Urea is only excreted in the urine, so if there is renal failure, the excretion is decreased and there is accumulation of urea in the extra and intracellular spaces.
C. Creatinine (plasma .6 - 1.2 mg/dl)
1. Is the end product of protein metabolism in the muscles.
2. Is completely filtered by the kidneys and excreted in the urine
3. Is a reliable index of renal function
4. Is not a reliable measure of glomerular filtration if the kidney is diseased as up to 20% can be secreted by the renal tubules
D. BUN/Creatinine ratio
1. Both need to be taken into consideration when assessing renal function
2. The normal ration is 10:1 - 15:1
3. An increase in BUN and creatinine is indicative of renal failure
4. An incease in BUN alone my be related to dehydration, decreased renal perfusion, or catabolism

Front 8

8. Describe the changes in the renal and urologic systems related to aging p1298

Back 8

As a person grows older, a decrease occurs in the number of nephrons. Both renal blood flow and glomerular filtration rate decline. Tubular transport and reabsoption decrease with age. Response to acidbase changes and reabsorption of glucose are delayed. Drugs eliminated by the kidney can accumulate in the plasma, causing toxic reactions.

Front 9

1. Discuss the types of kidney stones and the affects of obstruction within the urinary tract. P1303

Back 9

Kidney Stones
1. Types
2. Pathophysiology
1. Contributing factors
2. Stone formation
3. Effects of urine pH on stone formation
4. Where stones usually form
3. Clinical Manifestations
4. Evaluation
5. Treatment

Front 10

2. Discuss the types of renal and bladder tumors, their pathogenesis, clinical manifestations, evaluation, and treatment p1308

Back 10

A. Renal Cell Carcinoma
1. Pathogenesis including etiology
2. Clinical manifestations
3. Evaluation and treatment
B. Bladder Tumors
1. Pathogenesis including etiology
2. Clinical manifestations
3. Evaluation
4. Treatment

Front 11

3. Identify the most common infectious agents associated with infections of the urinary tract. P1311

Back 11

A. Causes
B. Types
1. Bacterial cystitis
a. Types
1. Hyperemic
2. Hemorrhagic
3. Suppurative
4. Ulcerative
b. Pathophysiology including etiology
c. Clinical manifestations
d. Evaluation and treatment
2. "Nonbacterial" cystitis
a. Urethral syndrome
b. Interstitial cystitis
3. Acute pyelonephritis
a. Defined - infection of the renal pelvis and the interstitium
b. Causes
c. Risk factors
1. Female
2. Urinary stasis or obstruction (prostatic enlargement, stones, anomalies)
3. Urinary catheters
4. Vesico-ureteral reflux
d. Pathophysiolgy
1. Infection is spread by the organism (usually E. coli) ascending up the ureters or via the blood stream
2. Renal medulla is infiltrated with white blood cells
3. These phagocytes release their lysozymes, free radicals
4. There is release of inflammatory mediators
5. Primarly affects the tubules
6. Rarely develops into acute renal failure
7. Heals with deposition of scar tissue and atrophy of affected tubules
e. Clinical manifestations
1. Signs and symptoms of lower urinary tract infections
2. Fever
3. Back (flank) pain (costovertebral tenderness)
4. Casts in urine - casts are made up of protein, WBCs, and inflammatory exudate. They actually are shaped like the renal tubule in which the cast has formed.
5. Increased sedimentation rate
6. Leukocytosis
7. Can experience a loss of the countercurrent mechanism with polyuria
f. Evaluation and treatment
g. Prognosis

Front 12

4. Compare and contrast acute and chronic pyelonephritis p1311

Back 12

1. Chronic pyelonephritis
a. Most often found in patients with some type of renal obstruction that has caused recurrent infections
b. Because of the small number of bacteria in the urine, think this chronic form of pyelonephritis is autoimmune and inflammatory with scarring of the kidneys
c. Pathophysiology
1. Dilated renal pelvis and calyces
2. Progressive nephron damage to renal insufficiency
d. Clinical manifestations
1. May be no signs and symptoms at first
2. Negative urine culture
3. May exhibit hypertension
4. Progression of this disease leads to renal failure
e. Evaluation and treatment

Front 13

5. Identify the most common cause of glomerulonephritis p1315

Back 13

A. Defined - An inflammatory injury to capillary membranes of the glomeruli
B. Etiology
1. Usually there is immune-mediated damage to the basement membrane of the glomerulus
2. Post-streptococcal infection is the most often cause of glomerulonephritis
a. 10 days to 3 weeks post streptococcal infection
b. Antigen/antibody (immune) complexes deposited in the basement membrane (precipitate out of the blood and get stuck in the microcirculation)
c. Activated complement attacks the epithelial cells which increases permeability of the glomerular membrane with leakage of protein and blood cells
d. Neutrophils and macrophages are recruited to the area, but add to the problem by phagocytizing the complexes and the basement membrane and releasing lysosomal enzymes
3. Autoimmune glomerulohephritis (Goodpasture syndrome)
a. B cell/complement mediated
b. Anti-glomerular basement membrane autoantibodies are made against the basement membrane of the glomerulus and the basement membrane of the lung
4. Post subacute bacterial endocarditis (streptococcal or staphylococcal)
5. Related to systemic connective tissue disorders such as systemic lupus
6. Idiopathic
C. Classification of Glomerulonephritis
1. Acute
a. Usually caused by post strep infection
b. Sudden onset
c. Person experiences hematuria, proteinurea, red blood cell casts, decreased GFR, decreased urinary output, edema (usually periorbital but also dependent edema of feet and legs), and hypertension
d. Usually recover without permanent renal damage
2. Rapidly progressive
a. Goodpasture's syndrome fits into this category
b. As the name implies, renal insufficiency has already happened by the time the disease is diagnosed
c. Proliferation of cells into the Bowman's space which become mixed with fibrin forming crescent shaped deposits in the vasculature of the glomerulus.
d. Experience hematuria, proteinurea, edema, hypertension
e. Poor prognosis and failure may be permanent
f. Prednisone (antiinflammatory) may not be effective and dialysis may be required.
3. Chronic glomerulonephritis
a. Glomerular disease that progresses to renal failure
b. Has been associated with hypercholesterolemia, lupus, insulin dependent diabetics
c. There is fibrosis of the glomerular membrane associated with proliferation of the cells that support the glomerular capillaries (mesangial cells)
D. Pathophysiology of Glomerulonephritis

Front 14

6. Diagram the pathophysiology of nephrotic syndrome from causation through complications p1320

Back 14

Defined - leaky glomerular membrane with loss of large amounts of protein (mostly albumin) in the urine (> 3.5 gm/day)
Etiology - processes which result in a leaky glomerular membrane
1. Glomerulonephritis
2. Diabetes Mellitus
3. Amyloidosis
4. Systemic lupus
Pathophysiology - see Fig 35-10 in text
Clinical Manifestations

Front 15

7. Differentiate among prerenal, intrarenal, and postrenal causes of acute renal failure p1322

Back 15

p1322

Front 16

8. Describe pathophysiology, clinical manifestations, treatment options, outcomes, and complications of acute renal failure p1322

Back 16

A. Acute Renal Failure (ARF) - a rapid deterioration in renal function characterized by progressive azotemia
1. Some interesting information
a. Approximately 5% of patients admitted to hospitals will develop ARF
b. Death occurs in about 30% of patients who develop ARF related to nephrotoxic agents
c. In patients who develop ARF secondary to surgery or trauma, the mortality rate is up to 50%
d. The mortality rate is around 80% in patients with respiratory failure who develop ARF
2. Definitions
a. Azotemia - high blood levels of nitrogenous wastes
b. Oliguria - <400 ml of urinary output in 24 hours
c. Nonoliguria - >400 ml of urinary output in 24 hours
d. Polyuria - > 6 liters of urinary output in 24 hours
e. Anuria - < 100 ml of urinary output in 24 hours
3. Etiology - divided into categories dependent upon the location of the cause of the ARF
a. Pre-renal - Most common type of ARF
1. Caused by anything that decreases the amount of blood that reaches the kidney resulting in poor renal perfusion to the kidney. The nephrons are intact, so with quick restoration of blood flow, the kidney can resume normal function. If flow is not restored in a timely manner, this will progress to acute tubular necrosis (ATN).

Front 17

9. Discuss the cellular abnormalities and multiple system manifestations of chronic renal failure p1325

Back 17

A. Etiology
1. Inflammatory response (glomerulonephritis)
2. Infections (pyelonephritis)
3. Toxins including lead poisoning
4. Urinary tract obstructions
5. Congenital or hereditary factors (polycystic or horse shoe kidneys)
6. Renal vascular disease (from diabetes, hypertension)
7. Prolonged renal ischemia
B. Stages of Chronic Renal Failure
A note: The kidneys have an amazing ability to adapt to damages, and over 90% of the nephrons have to be destroyed before the person enters end-stage renal failure. It is theorized that the intact nephrons take over, and actually over work and hypertrophy to compensate for the progressive loss of nephrons. It also only makes sense that if the damage is to the medulla where the countercurrent mechanism and the functioning tubules are, there will be salt and water wasting and trouble concentrating urine. If the damage is to the vascular glomerulus, there will be increased capillary fragility with red blood cells, white blood cells, and protein escaping and thus being excreted.
1. Decreased renal reserve
a. Up to 75% of the nephrons have been destroyed
b. There are minimal clinical manifestations
c. The BUN and creatinine levels are normal
2. Renal insufficiency
a. Up to 90% of the nephrons have been destroyed
b. The countercurrent mechanism fails as the long loops that maintain osmolality in the interstitium are progressively destroyed and are no longer enough functioning.
c. There is polyuria and nocturia
d. Azotemia begins
3. End-stage renal failure
a. Over 90% of the nephrons have been destroyed
b. Oliguria
c. Azotemia - uremia
d. Fixed specific gravity of the urine (1.010). It will be the same as plasma as whatever is filtered is excreted
C. The Uremic Syndrome

Front 18

1. Identify how disturbances of fluid and electrolyte balance can be life threatening in children p1339

Back 18

A. Renal Distribution of blood flow
1. Primarily to the medulla
2. Loops are short
3. High blood flow
a. The combination of the above accounts for a more dilute urine and decreased urea excretion
B. Narrow Chemical Safety Margin
1. High hydrogen ion concentration
2. Immature tubules with diminished response to ADH
3. The ability to secrete hydrogen ions, absorb bicarb, or buffer hydrogen with ammonia is not efficient
C. Body Fluid Distribution
1. % of extracellular body fluid twice that of an adult
2. 50% extracellular fluid exchange, compared to 14% in the adult
D. Composition of Body Fluids
1. Electrolyte composition in the extracellular fluid is greater in the newborn than the adult
2. The concentration of bicarb is lower resulting in a mild acidotic state
3. Lower plasma protein level

Front 19

2. Discuss the physiologic rational for the limited urine-concentrating ability in infants p1337

Back 19

p1337

Front 20

3. Describe the common congenital anomalies that occur within the renal and urologic systems p1339

Back 20

Hypospadias
Epispadias
Exstrophy of the bladder
1. Note that the bladder is actually inside out on the abdominal wall
2. Urine flows onto the skin causing excoriation
3. The bladder mucosa become inflammed, edematous, painful, and bleeds easily
4. Surgical intervention is necessary
Hypoplastic or Dysplastic Kidney
Renal Agenesis

Front 21

4. Compare and contrast the cellular pathophysiology and clinical signs and symptoms of nephrotic syndrome, glomerulonephritis, and hemolytic-uremic syndrome in children p1342

Back 21

A. Nephrotic Syndrome
1. It is unkown what causes this syndrome in children
2. The glomeruli look normal except for fusion of podocytes in the epithelium
3. The glomerular membrane is leaky with loss of protein leading to edema and hyperlipidemia
4. It usually occurs in boys between the age of 2 and 3 years of age
5. It is usually a primary disease
6. The clinical manifestations include:
a. Edema, beginning with periorbital, then extending to the rest of the body
b. Frothy urine
c. Pleural effusions
d. Pale
e. Blood pressure is usually normal.
f. Increase susceptibility to infection related to loss of protein
7. Diagnosis
a. Proteinurea
b. Low serum protein levels
c. Hyperlipidemia with lipidurea
d. May require a kidney biopsy
8. Treatment
a. The goal is to reduce the amount of protein loss
b. Predisone
c. Diuretics
d. Low sodium diet
e. Immunosuppressive agents
f. There is usually complete recovery from this disease process
B. Poststreptococcal Glomerulohephritis
1. An immune response to group A beta hemolytic strep post pharyngeal or skin infection
2. Rapid onset
3. Urine will display gross hematuria
4. Clinical manifestations
a. Edema
b. Hypertenstion
c. Coca cola colored urine
d. Flank or mid abdominal pain
e. Fever
f. Malaise
g. Central nervous system manifestations to seizures
h. Manifestations of fluid overload
5. Treatment
a. Treat the symptoms
b. May give antibiotics. Treatment of strep infections with antibiotics does not stop the development of the disease
c. Fluid, potassium and sodium restriction
d. Antihypertensives and diuretics
e. 95% of the kids do recover
C. Hemolytic-Uremic Syndrome
1. The most common cause of acute renal failure in infants and children < 4 years-of-age
2. Pathophysiology
a. Endothelial lining of the arterioles of the glomerulus get plugged with platelets and fibrin clots.
b. The red blood cells get damaged as they go through the narrowed arterioloes
c. These damaged RBCs get removed by the spleen, thus causing hemolytic anemia
d. The platelets clumping together in the arterioles along with removal of the platelets cause thrombocytopenia
e. There are fibrin split products in the serum and the urine related to fibrinolysis of the fibrin clots
f. Brain, liver, heart, and intestines often involved
3. Clinical manifestations
a. Usually follows a GI or upper respiratory illness with E. coli most often the culprit
b. Sudden onset of oliguria, purpura, pallor
c. May experience splenomegaly and jaundice
d. If brain is involved may experience irritability, lethargy, seizures
e. If intestines are involved, may experience watery bloody diarrhea
f. Circulatory overload
g. Renal failure manifestations of metabolic acidosis, azotemia, hyperkalemia, and hypertension
4. Treatment
a. Adequate nutrition
b. Maintaining fluid and electrolyte balance
c. Control of blood pressure and seizures
d. Peritoneal dialysis if renal failure occurs
e. Blood transfusions may be needed, but because the patient is already in fluid overload, the transfusions are given judiciously. The hemoglobin is watched and will probably be kept at about 8 or 9, rather than at a normal level.

Front 22

5. Describe the structural defects that result in vesicoureteral reflux p1346

Back 22

Vesicoureteral Reflux
1. Defined
2. Who is usually effected
3. Grades of reflux
4. Pathophysiology
5. Clinical manifestations
6. Diagnosis
7. Treatment

Front 23

6. Discuss the pathogenesis, clinical signs and symptoms, evaluation, and treatment of Wilms tumor p1347

Back 23

A. Defined
B. Peak incidence
C. Pathophysiology
1. Deletion or inactivation of tumor suppressor genes on the short arm of chromosome 11 occurs in the sporadic form of nephroblastoma
2. In the inherited form (autosomal dominant), the gene is located on chromosome 16
3. The gene is lost in the fetal cells that normally differentiate into the tubules and the glomeruli
4. Other congenital anomalies are found in 18% of the children who have Wilms tumor
D. Clinical Manifestations
1. Painless enlarging abdominal mass
2. Child may experience fever, hematuria, hypertension
E. Diagnosis
1. Palpable abdominal mass
2. Abdominal ultrasound
3. Abdominal CT scan
4. Based on tumor biopsy
F. Staging (see Table 37-4, page 1348 in text)
G. Treatment
1. Surgical resection of the tumor
2. Tumor is radiosensitive, so radiation therapy is very effective if started shortly after surgery
3. Chemotherapy and bone marrow transplant has been used for advanced stages of the disease.
4. Prognosis is good if caught early and there has not been metastasis to the brain, liver, or bone

Front 24

7. Discuss enuresis

Back 24

A. Defined
B. Types
C. Theories of the causes
D. Mechanisms for control and treatment of enuresis