Renal II: Renal Failure and Bladder Function

1
Renal Pathophysiologyand Bladder Dysfunction
2
Clinical Assessment of Renal Function
3
Clinical Assessment of Renal Function

• Glomerular Filtration Rate
• Blood urea nitrogen
• Serum creatinine
• Creatinine clearance
• Renal Tubular Function and Integrity
• Urine Concentrating Ability
• Proteinuria
• Urinary Sodium Excretion

4
Clearance
5
Clearance

• An imaginary quantity
• Physical there is no such thing as clearance
• Normally performed as a 24-hour urine collection
• The clearance of a solute - the virtual volume
  of blood that would be totally cleared of a
  solute in a given time.
• The rate at which the kidneys excrete solute into
  urine rate at which solute disappears from
  blood plasma.
• Solutes come from the blood perfusing the
  kidneys.
• For solute X

Conc. of X in urine
Volume of urine formed in given time
?
Cx Ux x V
Conc. of X in systemic blood plasma
Px
Clearance
6
Measurement of GFR
7
Measurement of GFR

• GFR is also assessed using principles of
  clearance.
• As the solute, we use creatinine because all of
  the creatinine that is filtered ends up in the
  urine and none of it is reabsorbed
• GFR - volume of fluid filtered into Bowmans
  capsule per unit time.
• Same equation, GFR is Cx if X has certain
  required properties (i.e. Ccreatinine).

Conc. of X in urine
Volume of urine formed in given time
?
GFR Ux x V
Conc. of X in systemic blood plasma
Glomerular filtration rate
Px
8
Clinical Assessment of Renal FunctionMetabolism
of Blood Urea Nitrogen (BUN)
9
Clinical Assessment of Renal FunctionMetabolism
of Blood Urea Nitrogen (BUN)

• Major nitrogenous end product of protein and
  amino acid catabolism
• Produced by liver and distributed throughout
  intracellular and extracellular fluid
• In kidneys almost all urea is filtered out of
  blood by glomerular function. Some urea
  reabsorbed with water (50) but most is removed
  in urine

10
Increased BUN
11
Increased BUN

• Dehydration
• There is a lack of fluid volume to excrete waste
  products
• High protein diet
• GI bleed
• Equivalent to a high protein diet because there
  are a lot of red blood cells
• Digested blood is a source of urea
• Anabolic Steroid use
• Impaired renal function
• The kidneys are less able to clear urea from the
  bloodstream
• CHF - poor renal perfusion
• Shock
• MI
• Excess protein catabolism

12
Decreased BUN
13
Decreased BUN

• Fluid excess - especially a concern with IV
  fluids
• SIADH
• Excess water is retained in the bloodstream
  inappropriately
• Trauma, surgery, opioids,
• Liver failure
• Urea is synthesized by the liver so liver
  problems lead to decreased synthesis
• If the liver is not working well, ammonia is high
• Malnutrition
• Anabolic steroid use
• Pregnancy - dilutional effects of having a
  higher blood volume

14
BUNBottom Line
15
BUNBottom Line

• Bottom line BUN is not really a good indicator
  of renal function since many other things can
  influence its levels.
• Multiple variables can interfere with the
  interpretation of a BUN value
• GFR and creatinine clearance are more accurate
  markers of kidney function.
• Age, sex, and weight will alter the "normal"
  range for each individual, including race.
• In renal failure or chronic kidney disease (CKD),
  BUN will only be elevated outside "normal" when
  more than 60 of kidney cells are no longer
  functioning.
• More accurate measures of renal function are
  generally preferred to assess the clearance for
  purposes of medication dosing.

16
Serum Creatinine
17
Serum Creatinine

• Normal values
• Men  0.8-1.3 mg/dL
• Women 0.6-1.0 mg/dL
•  
•  
•  

18
Creatinine Metabolism
19
Creatinine Metabolism

• Creatinine is a waste product of creatine
  phosphate metabolism by skeletal muscle tissue. 
• The amount of muscle that a person has is
  proportional to muscle mass.

20
Increased Creatinine
21
Increased Creatinine

• Occurs only with a loss of more than 50 of
  nephrons
• Impaired renal function
• Chronic nephritis
• Urinary tract obstruction
• Muscle diseases such as gigantism, acromegaly,
  and myasthenia gravis because there are issues
  with muscles breaking down and releasing a lot of
  creatinine
• Congestive heart failure
• Shock

22
Decreased Creatinine
23
Decreased Creatinine

• Elderly
• Persons with small stature, decreased muscle mass
  
• Inadequate dietary protein
• Muscle atrophy

24
Serum CreatinineBottom Line
25
Serum CreatinineBottom Line

• Serum creatinine measurements are a good first
  approximation of renal function. It is better
  than BUN but is not as good as creatinine
  clearance

26
Creatinine Clearance Test
27
Creatinine Clearance Test

• Normal values
• 110-115 mL/min
•  
• Creatinine clearance - the total amount of
  creatinine excreted in urine in a 24 hour period
• Creatinine is excreted entirely by the kidneys
  and is not reabsorbed in the tubules.
• Therefore, it is directly proportional to the
  glomerular filtration rate (GFR). 
• So clinically it can be seen as a measure of
  GFR. 

28
Changes in Creatinine Clearance
29
Changes in Creatinine Clearance

• With unilateral kidney disease or nephrectomy, a
  decreased creatinine clearance is NOT expected if
  the other kidney is normal
• During renal failure, diminished glomerular
  filtration occurs
• Increases the retention of creatinine in the
  serum.
• When chronic renal failure and uremia becomes
  very severe, an eventual reduction occurs in the
  excretion of creatinine by both the glomeruli and
  the tubules.
• Bottom line Creatinine clearance is the gold
  standard measurement of renal function because
  it is a measure of the GFR.

30
Assessment of Renal Tubular Function and Integrity
31
Assessment of Renal Tubular Function and Integrity

• The tubules are responsible for urine
  concentration
• Resorb a lot of solutes and a lot of water
• Does this to control the ECF, not to produce
  urine
• Urine specific gravity 1.003-1.030

32
Factors that Can Influence the Concentration
Gradient
33
Factors that Can Influence the Concentration
Gradient

• 1) Decreased sodium absorption
• Chronic polyuria (e.g. diabetes insipidus,
  diabetes mellitus)
• Altered sodium resorption (e.g. Addison's
  disease).
• 2) Lack of ADH
• ADH increases the permeability of the tubules to
  water and urea
• A lack of ADH decreases the permeability of the
  tubules
• Hypokalemia
• Hypercalcemia
• 3) Increased medullary blood flow
• Causes medullary solute washout, because the vasa
  recta is critical in maintaining the medullary
  interstitial gradient
• Hypokalemia
• Hypercalcemia
• Thyroid hormone

34
Assessment of Glomerular Function and Integrity
35
Assessment of Glomerular Function and Integrity

• Proteinuria- protein in the urine
• Types
• Transient
• Orthostatic
• Persistent

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Transient Proteinuria
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Transient Proteinuria

• Transient- resolves with treatment of underlying
  condition
• May occur with fever, CHF, seizure, exercise
• This is of no consequence
• Single tests need to be repeated to verify
  findings

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Orthostatic Proteinuria
39
Orthostatic Proteinuria

• Not associated with deteriorating renal function.
• Increased protein excretion in the upright
  position and normal protein excretion in the
  supine position

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Persistent Proteinuria
41
Persistent Proteinuria

• Persistent- indicates significant renal disease
• Glomerular- alterations in basement membrane
  filtration
• Due to increased filtration of albumin and other
  macromolecules across the glomerular basement
  membrane
• Occurs because of an alteration in the charge
  selectivity and size selectivity of the
  glomerular barrier
• Tubular- impairment of tubular reabsorption
  (amino acid nuria)

42
Types of Dysfunctions that Cause Renal Disease
43

• Types of Dysfunctions that Cause Renal Disease
• First question when you have a patient with renal
  problems
• Pre-renal
• Intra-renal (Intrinsic)
• Post-renal

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Pre-Renal Dysfunction
45
Pre-Renal Dysfunction

• Decreased blood flow to kidney (most common form)
• If the kidney does not get enough blood, it
  cannot function properly
• Causes
• Hemorrhage
• ? Cardiac Output (CO)
• Dehydration
• Loss of fluids
• Shock

46
Intra-Renal Dysfunction
47
Intra-Renal Dysfunction

• Disorders that disrupt the structures of the
  kidney
• Causes
• Ischemia
• Drugs
• Glomerular disease
• Intratubular obstruction
• Toxins from infection

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Post-Renal Dysfunction
49
Post-Renal Dysfunction

• Disorders that impair urine outflow from the
  kidneys
• Ureteral obstruction
• Obstruction of the ureters or the urethra

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Pre-renal Causes of Kidney Dysfunction
51
Pre-renal Causes of Kidney Dysfunction

• Kidneys receive 25 of CO to filter blood they
  regulate fluids and electrolytes.
• ?Renal Blood Flow (RBF) ?
• ? Glomerular Filtration Rate (GFR) ? ? urine
  output (u/o)
• ?RBF ? ?02 delivery to tubular cells ? cell death
• The glomeruls efferent arteriole leads to another
  capillary bed that nourishes the tubule
• ?RBF ? ? GFR, ? filtration of substances,
  ?substances in blood ???Cr, ?BUN

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Intrinsic Causes of Renal Dysfunction
53
Intrinsic Causes of Renal Dysfunction

• Conditions that cause damage to structures within
  kidney
• glomeruli, interstitium, tubules
• Injury to tubules most common
• Injury to glomeruli

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Intrinsic Causes of Renal DysfunctionInjury to
Tubules
55
Intrinsic Causes of Renal DysfunctionInjury to
Tubules

• Ischemia
• Toxic insult (drugs)
• Obstruction

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Intrinsic Causes of Renal DysfunctionInjury to
Glomeruli
57
Intrinsic Causes of Renal DysfunctionInjury to
Glomeruli

• Diabetes
• The most common cause of glomerular disease
• Autoimmune disease

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Immune Mechanisms of Glomerular Disease
59
Immune Mechanisms of Glomerular Disease
Antigens Exogenous or endogenous to the
kidney. Immune complexes set up intense
inflammation that damages the BM.
Porth, 2007, Essentials of Pathophysiology, 2nd
ed., Lippincott, p. 550
60
Anti-Glomerular Membrane Antibodies
61
Anti-Glomerular Membrane Antibodies

• Antiglomerular antibodies leave circulation,
  react with antigens present in BM of glomerulus.
• Autoantibodies react to structures of the
  glomerulus, most commonly the basement membrane

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Circulating Antigen-Antibody Complex Deposition
63
Circulating Antigen-Antibody Complex Deposition

• Antigen-antibody complexes circulating in
  blood become trapped as they are filtered in
  glomerulus.
• Circulating immune complexes are bound to an
  antigen
• Because they are bound to antigen, they have the
  capability of evoking an immune response
• Clogged up and lodge in the kidney, leading to an
  inflammatory response in the glomeruls

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End Result of the Immune Mechanisms of Glomerular
Disease
65
End Result of the Immune Mechanisms of Glomerular
Disease

• The end result is the same...the only difference
  is the location of the antigen
• Left part of the kidney, right can be anywhere,
  circulating
• The commonality is that inflammation occurs,
  damaging the basement of the glomerulus

66
IntrinsicGlomerular Disorders
67
IntrinsicGlomerular Disorders

• Glomerular disorders affect glomerular capillary
  structures that filter material from the blood.
• Nephritic syndromes
• Nephrotic syndromes

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Nephritic Syndromes
69
Nephritic Syndromes

• Nephritic syndromes are caused by diseases that
  produce proliferative inflammatory responses that
  decrease the permeability of the capillary
  membrane.
• This is usually because the membrane thickens

70
Nephrotic Syndromes
71
Nephrotic Syndromes

• The nephrotic syndrome is caused by disorders
  that increase the permeability of the glomerular
  capillary membrane, causing massive loss of
  protein in the urine.
• This makes the membrane too porous
• Disorders may be nephritic and then nephrotic or
  nephrotic and then nephritic

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Acute Proliferative Glomerulonephritis
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Acute Proliferative Glomerulonephritis
Hematuria Proteinuria RBC Casts shape of the
tubule because so many rbcs were in the tubule
nephrotic syndrome
Infection with streptococci
Edema Hypertension, HF Encephalopathy Renal
Failure
Immune complexes/antigens glom onto the strep,
creating circulating complexes that become
entrapped in the glomerular membrane
Oliguria,Na and H2O retention Hypervolemia
nephritic syndrome
Activation of complement Recruitment of leukocytes
Inflammation and Swelling Of capillary membrane
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Other Nephritic Syndromes
75
Other Nephritic Syndromes

• Rapidly Progressive Glomerulonephritis
• IgA Nephropathy (i.e. Buerger disease)
• As nephritic syndromes worsen, they may progress
  to nephrotic syndromes and vice versa.

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Rapidly Progressive Glomerulonephritis
77
Rapidly Progressive Glomerulonephritis

• Caused by a number of immunologic disorders
• Systemic lupus erythematosis
• Goodpasture syndrome
• The antibody-antigen complex leads to
  inflammation, which then destroys the glomerulus

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IgA Nephropathy (i.e. Buerger disease)
79
IgA Nephropathy (i.e. Buerger disease)

• Deposition of IgA immune complexes in mesangium

80
Symptoms of Nephrotic Syndromes
81
Symptoms of Nephrotic Syndromes

• Proteinuria
• Lipiduria
• Hypoalbuminemia
• Edema
• Hyperlipidemia
• The hallmark of a nephrotic syndrome is
  proteinuria
• When proteins pass into the urine, their
  concentration decreases in the blood, leading to
  edema
• This is because there is not enough osmotic
  pressure pulling the fluid back into the venous
  capillary

82
Nephrotic Disorders
83
Nephrotic Disorders

• Membranous Glomerulonephritis
• Thickening of GBM due to immune complexes
• Minimal Change Disease (Lipoid Nephrosis)
• Diffuse loss of foot processes from the
  epithelial layer of the glomerular membrane.
• Focal Segmental Glomerulosclerosis
• Sclerosis of some glomeruli. (Alonzo Mourning)

84
Diabetic Nephropathy
85
Diabetic Nephropathy
Hyperglycemia
Hyperfiltration Hyperperfusion
Microalbuminuria
Increased messangial cell matrix production
hypertrophy
GBM thickens
Glomerular sclerosis
Renal Failure
86
Diabetic NephropathyDescription
87
Diabetic NephropathyDescription

• Diabetes damages the basement membrane because of
  the high glucose
• Glucose can attach itself to proteins
• One of the first signs is microalbuminuria caused
  by increased permeability of the basement
  membrane
• This is an increase in GFR
• Can test the urine for small amounts of albumin
• Treat this by putting them on an ACE inhibitor in
  order to retard the nephropathy
• Then GBM thickens, leading to renal failure
• Occurs when the kidney leaks small amounts of
  albumin into the urine
• In other words, when there is an abnormally high
  permeability for albumin in the renal glomerulus.
• An important prognostic marker for kidney disease
  in diabetes mellitus

88
Hypertensive Glomerular Disease
89
Hypertensive Glomerular Disease

• Hypertension is a cause and effect of kidney
  disease
• Everyone with renal failure has hypertension
• ? glomerular structure (sclerosis) ? thick vessel
  walls ? ? perfusion of the nephron ? ?BUN and
  proteinuria
• BUT as RBF declines, the kidney secretes renin,
  activating the RAAS, thereby raising BP further.

90
Hypertension and the Kidneys
91
Hypertension and the Kidneys

• Hypertension causes renal failure
• High pressure on the glomerulus causes it to
  thicken, which decreases perfusion of the nephron
  and increases the BUN
• Because the glomerulus is damaged, there will be
  proteinuria
• Kidney senses damage and secretes renin
• Creates angiotensin II, which raises the blood
  pressure
• May restore renal blood flow for a while but then
  destroys the kidney further as well
• The RAAS will become more active and lead to
  higher blood pressure

92
Intratubular Obstruction
93
Intratubular Obstruction

• Myoglobin
• Hemoglobin
• Large amounts of uric acid or protein

94
Myoglobin
95
Myoglobin

• Myoglobin stores oxygen for the skeletal muscle
  to use
• Rhabdomyolosis leads to liberation of the
  myoglobin, which will clog up the tubules
• Skeletal muscle breakdown from trauma, exertion,
  hyperthermia, prolonged seizures, statins and
  fibrin derivatives.

96
Hemoglobin
97
Hemoglobin

• Hemolysis, including blood transfusion reactions,
  liberates the hemoglobin and causes tubular
  obstruction

98
Large Amounts of Uric Acid or Protein
99
Large Amounts of Uric Acid or Protein

• Widespread cancer, such as leukemia and multiple
  myeloma
• Massive tumor destruction with chemotherapy
  liberates all of the contents of the blood cells
  into the blood
• Radiation (tumor lysis syndrome)

100
Postrenal Causes of Renal Failure
101
Postrenal Causes of Renal Failure

• Obstruction of urine outflow from kidneys
• Ureters
• Calculi, strictures
• Bladder
• Tumors, neurogenic bladder
• Urethra
• Prostatic hypertrophy may lead to urine backing
  up into the kidneys
• Strictures

Porth, 2007, Essentials of Pathophysiology, 2nd
ed., Lippincott, p. 540
102
Mechanisms of Renal Damage Due to Obstruction
103
Mechanisms of Renal Damage Due to Obstruction

• For the post-renal causes and pre-renal causes,
  if you reverse the cause pretty quickly, the
  kidney can get back to normal fairly quickly
• Kidney damage depends on
• Degree of obstruction
• Partial vs. complete unilateral vs. bilateral
• Duration of the obstruction

104
Most Damaging Effects of Obstruction
105
Most Damaging Effects of Obstruction

• Stasis of urine, bacteria ascend urethra?
  infection, stone formation
• Development of back pressure ?Decreased renal
  blood flow, destroys kidney tissue

106
ObstructionDiagram
107
Hydronephrosis is distention (dilation) of the
kidney with urine, caused by backward pressure on
the kidney when the flow of urine is obstructed.

• Marked/complete obstruction ? ? back pressure due
  to continued glomerular filtration, impedance to
  urine flow
• Hydroureter
• Obstruction in distal ureter ? ? pressure above
  it ? dilation of ureter
• Hydronephrosis
• Urine-filled dilatation of renal pelvis

Merck Manual
The panels show the right and left kidneys of a
patient. Note the dilated pelvis and calyces on
the right compared to the left. A tumor caused
an outflow obstruction on the right, resulting in
hydronephrosis.
108
Manifestations of Obstruction
109
Manifestations of Obstruction

• Pain
• Usually the reason for seeking medical care
• Result of distention of bladder, collecting
  system, renal capsule.
• Signs of urinary tract infection

110
Nephrolithiasis
111
Nephrolithiasis

• The fancy name for kidney stones
• Crystalline structures made up of materials the
  kidney normally excretes in urine
• The etiology of stone formation is complex and
  not well understood
• Usually people who get one stone usually get
  multiple ones
• ? Why usually unilateral?
• ? Urine is saturated with stone components?
• Calcium salts, Magnesium-ammonium phosphate,
  cystine, uric acid
• ? Organic materials produced by epithelial cells?
• ? Lack of proteins that inhibit crystallization?

112
Stones
113
Stones

• Calcium oxalate, calcium phosphate
• Associated with hypercalcemia
• Hyperparathyroidism
• Vitamin D intoxication
• Diffuse bone disease
• Immobility
• Renal tubular acidosis will favor stone formation

114
A 58-year-old man presented with a 1 year history
of dysuria
115
A 58-year-old man presented with a 1 year history
of dysuria
Rajaian S and Kekre N. N Engl J Med 20093611486
Rajaian S and Kekre N. N Engl J Med 20093611486
116
Manifestations of Stones
117
Manifestations of Stones

• Renal Colic
• Noncolicky Renal Pain

118
Renal Colic
119
Renal Colic

• Stretching of the collecting system/ureter.
• Stones (1-5mm) move into ureter, obstruct flow.
• Acute, intermittent, excruciating pain in flank
  on affected side.

120
Noncolicky Renal Pain
121
Noncolicky Renal Pain

• Not as much pain
• Stones that produce distention of the renal
  calyces/pelvis.
• Dull ache in flank, mild to severe
• Worsens with fluid intake.

122
Treatment of Small Stones
123
Treatment of Small Stones

• Treatment depends on the type and cause of the
  stone. Most stones can be treated without
  surgery. Stones less than 5 mm in size usually
  will pass spontaneously.
• Drinking lots of water (two and a half to three
  liters per day) and staying physically active are
  often enough to move a stone out of the body.
• However, if there is infection, blockage, or a
  risk of kidney damage, a stone should always be
  removed. Any infection is treated with
  antibiotics first. Nonsteroidal anti-inflammatory
  drugs or opioids are used for pain control, along
  with a stool softener.

124
Treatment of Larger Renal Stones
125
Treatment of Larger Renal Stones

• Stones greater than 6 mm will require some form
  of intervention, especially if the stone is
  stuck, causing obstruction and infection of the
  urinary tract.
• Extracorporeal Shock Wave Lithotripsy (ESWL)
• Ureteroscopic Stone Removal
• Percutaneous Nephrolithotomy (PCNL)

126
Extracorporeal Shock Wave Lithotripsy (ESWL)
127
Extracorporeal Shock Wave Lithotripsy (ESWL)

• This is the most common method
• Does not involve a surgical operation.
• Ultrasound waves are used to break the stones
  into crystals small enough to be passed in the
  urine.
• The shock waves do not hurt
• Some people feel some discomfort at the time of
  the procedure and shortly afterwards.

128
Ureteroscopic Stone Removal
129
Ureteroscopic Stone Removal

• If a stone is lodged in the ureter, a flexible
  narrow instrument called a cystoscope can be
  passed up through the urethra and bladder.
• The stone is "caught" and removed, or shattered
  into tiny pieces with a shock wave.
• This procedure is usually done under a general
  anesthetic.

130
Percutaneous Nephrolithotomy (PCNL)
131
Percutaneous Nephrolithotomy (PCNL)

• If ESWL does not work or a stone is particularly
  large, it may be surgically removed under general
  anesthetic.
• The surgeon makes a small cut in the back and
  uses a telescopic instrument called a nephroscope
  to pull the stone out or break it up with shock
  waves.

132
Renal Failure
133
Renal Failure

• Condition in which the kidneys fail to remove
  metabolic end products from the blood and
  regulate the fluid, electrolyte, and pH balance
  of the extracellular fluids.
• Underlying cause may be renal disease or systemic
  disease.
• Can occur as acute or chronic

134
Types of Renal Failure
135
Types of Renal Failure

• Acute
• Abrupt in onset
• Usually reversible with early treatment
• Chronic
• End result of irreparable damage to the kidneys
• Develops over the course of years

136
Acute Renal Failure (ARF)
137
Acute Renal Failure (ARF)

• Azotemia
• Accumulation of nitrogenous waste products (urea)
  in blood.
• Urea, nitrogen, creatinine
• Both the BUN and the creatinine would go up
• ?GFR ? ? urine excretion of wastes? ? Blood
  urea nitrogen (BUN), ? Blood Creatinine (Cr).
• Many causes
• Acute tubular necrosis is one

GFR

• BUN
• Cr

McCance (2002) Figure 34-6 pg. 1175
138
Acute Tubular Necrosis (ATN)
139
Acute Tubular Necrosis (ATN)

• Very common in hospitalized patient
• Characterized by destruction of tubular
  epithelial cells ? ? tubular functions
• Most common cause of intrinsic renal failure
• Risk
• Elderly, diabetics, poor renal perfusion
• Tubular injury is usually reversible

140
Causes of Acute Tubular Necrosis
141
Causes of Acute Tubular Necrosis

• Ischemia, such as from shock
• Nephrotoxic drugs
• Tubular obstruction
• Ex. myoglobin and hemoglobin
• Toxins from infectious agents

142
Three Phases of ATN
143
Three Phases of ATN

• Onset/initiating
• Maintenance Phase
• Recovery Phase

144
Onset/Initiating Phase
145
Onset/Initiating Phase

• Hours/days from onset of insult
• Gradual
• Urine output will decrease slowly

146
Maintenance Phase
147
Maintenance Phase

• ? GFR
• Retention of metabolites (urea, K, sulfate, Cr),
  ? U/O
• Generalized edema
• Pulmonary edema
• Metabolic acidosis
• Because the kidney is not working to rid the body
  of acid
• Everything is clogged up and a lot of times the
  person will not produce any urine at all

148
Recovery Phase
149
Recovery Phase

• Repair of renal tissues
• Gradual improvement in U/O, BUN, and creatinine

150
Chronic Renal Failure
151
Chronic Renal Failure

• Progressive, irreversible destruction of nephrons
  over many years.
• Requires dialysis, kidney transplants.
• Causes
• Diabetes, hypertension, glomerulonephritis
• Signs and symptoms are not evident until disease
  is advanced.

Porth, 2007, Essentials of Pathophysiology, 2nd
ed., Lippincott, p.564
152
Chronic Renal FailureStages of Progression
153
Chronic Renal FailureStages of Progression

• Diminished Renal Reserve
• Renal Insufficiency
• Renal Failure
• End-Stage Renal Disease (ESRD)

154
Diminished Renal Reserve
155
Diminished Renal Reserve

• GFR 50 of normal and BUN/Cr are normal
• No signs/symptoms

156
Renal Insufficiency
157
Renal Insufficiency

• GFR 20-50 of normal
• Azotemia
• Anemia
• Hypertension

158
Renal Failure
159
Renal Failure

• GFR lt 20
• ? fluid/electrolyte regulation
• Metabolic acidosis
• Other systems fail

160
End-stage Renal Disease
161
End-stage Renal Disease

• GFR lt 5 normal
• Atrophy/fibrosis of kidneys
• Dialysis or transplant required

162
Signs and Symptoms of Renal Failure
163
Signs and Symptoms of Renal Failure

• Fluid and electrolyte imbalance
• Increase in blood levels of metabolic acids and
  other small, diffusible particles (e.g. urea)
• Anemia - erythropoietin is missing
• Hyperparathyroidism
• Vitamin D and calcium in the kidney are not
  working so the parathyroid gland secretes more
• Cardiovascular effects
• Activation of renin-angiotensin mechanism,
  leading to increased vascular volume
• Fluid retention and hypoalbuminemia
• Excess extracellular fluid volume, left
  ventricular hypertrophy and anemia
• Body fluids
• Hematologic

164
Signs/Symptoms of Renal FailureFluid and
Electrolyte Imbalance
165
Signs/Symptoms of Renal FailureFluid and
Electrolyte Imbalance

• Fluid and electrolyte imbalance
• Increases in blood levels of metabolic acids and
  other small, diffusible particles (urea)
• Signs of uremic encephalopathy
• Lethargy
• Decreased alertness
• Loss of recent memory
• Delirium
• Coma
• Seizures
• Asterixis
• Muscle twitching
• Tremulousness
• Signs of neuropathy
• Restless leg syndrome
• Paresthesias
• Muscle weakness and atrophy

166
Signs/Symptoms of Renal FailureAnemia,
Hyperparathyroidism, High Concentrations
167
Signs/Symptoms of Renal FailureAnemia,
Hyperparathyroidism, High Concentrations

• Anemia
• Because erythropoietin is missing
• Hyperparathyroidism
• Vitamin D and calcium in the kidney are not
  working so the parathyroid gland secretes more
• High concentration of metabolic end products in
  body fluids
• Pale, sallow complexion
• Pruitus
• Uremic frost and odor of ammonia on skin and
  breath

168
Consequences of Renal FailureCardiovascular
169
Consequences of Renal FailureCardiovascular

• Activation of the RAAS and increased vascular
  volume
• Hypertension that must be treated
• Everybody with kidney failure has hypertension
  because the RAAS is working over time
• Fluid retention and hypoalbuminemia
• Leads to edema
• Dialysis is required
• Excess extracellular fluid volume
• Left ventricular hypertrophy and anemia
• CHF
• Pulmonary edema
• Dialysis is required

170
Consequences of Renal FailureBody Fluids
171
Consequences of Renal FailureBody Fluids

• Decreased ability to synthesize ammonia and
  conserve bicarbonate
• Metabolic acidosis
• Dialysis is required
• Inability to excrete potassium
• Hyperkalemia and dialysis
• Inability to regulate sodium excretion
• Salt wasting or sodium retention and dialysis
• Impaired ability to excrete phosphate
• Hyperphosphatemia and dialysis
• Osteoporosis
• Impaired phosphate excretion and inability to
  activate vitamin D
• Hypocalcemia and increased levels of PTH

172
Consequences of Renal FailureHematologic
173
Consequences of Renal FailureHematologic

• Impaired synthesis of erythropoietin and effects
  of uremia
• Anemia
• Impaired platelet function
• Bleeding tendencies

174
Dialysis
175
Dialysis
176
Renal Failure and the Elimination of Drugs
177
Renal Failure and the Elimination of Drugs

• Kidneys are responsible for elimination of drugs
  and their metabolites
• Renal failure and its treatment interfere with
  elimination of drugs
• Decreased elimination allows some drugs to
  accumulate in blood dosages may need to be
  adjusted
• A type 2 diabetes drug that is eliminated
  completely by the kidney is metformin
• People with renal failure cannot take metformin

178
The maintenance phase of acute tubular necrosis
(ATN) is characterized by
179
The maintenance phase of acute tubular necrosis
(ATN) is characterized by

1. Hypokalemia
2. Diuresis
3. Edema
4. Discolored urine

180
Control of Urine Elimination and Disordersof
the Bladder
181
Control of Urine Elimination
182
Control of Urine Elimination

• Urine formation is a by-product of the normal
  functioning of the kidneys, whose main function
  is to maintain the acid-base balance and ion
  concentrations in the blood.
• The urine is whatever is left over from the
  processes of the kidney
• The bladder stores urine and controls its
  elimination from the body

183
Alterations in Urine Elimination
184
Alterations in Urine Elimination

• Neurogenic bladder an inability to urinate
• The bladder does not contract properly
• Incontinence urinate too much, in the wrong
  place, or at the wrong time

185
Four Layers of Bladder
186
Four Layers of Bladder

• Outer serosal layer
• Detrusor muscle
• Network of smooth muscle fibers
• Submucosal layer of loose connective tissue
• Inner mucosal lining of transitional epithelial
  cells
• Acts as a barrier to prevent the passage of water
  between the bladder contents and blood

Porth, 2007, Essentials of Pathophysiology, 2nd
ed., Lippincott, p. 576
187
Description of the Bladder
188
Description of the Bladder

• The bladder has a lot of layers that expand as it
  fills with urine
• The urine is propelled down the ureters by
  peristalsis
• When it gets to the bladder, the bladder squeezes
  the ureters
• The bladder is made of smooth muscle lined by
  epithelium (transitional epithelium)
• The area at the bladder neck is called the
  trigone
• There is an internal sphincter (smooth muscle)
  and an external sphincter (skeletal muscle,
  voluntary control)

189
Motor Control of Bladder Function
190
Motor Control of Bladder Function

• Detrusor muscle
• Muscle of micturition (smooth muscle)
• Contracts?urine is expelled from bladder under
  ANS control
• Abdominal muscles
• Contraction ? ? intra-abdominal pressure ? ?
  bladder pressure
• Internal sphincter
• Circular smooth muscles in bladder neck
  continuation of detrusor. Bladder relaxed, these
  fibers are closed and act as sphincter. When
  detrusor contracts, sphincter is pulled open by ?
  in bladder shape under ANS control
• External sphincter
• Circular skeletal muscle that surrounds urethra,
  acts as a reserve mechanism to stop micturition
  maintains continence despite ? bladder pressure
  skeletal muscle is under voluntary control

191
Neural Control of Bladder FunctionNervous System
Control
192
Neural Control of Bladder FunctionNervous System
Control

• ANS and Voluntary control
• Parasympathetic Nervous System (PSNS)
• Sympathetic Nervous System (SNS)

193
Parasympathetic Nervous System
194
Parasympathetic Nervous System

• Excitatory input to the bladder ?bladder emptying
• Relaxes internal sphincter
• The PNS is the mechanism for emptying the bladder

195
Sympathetic Nervous System
196
Sympathetic Nervous System

• Relaxes bladder smooth muscle
• Contracts internal sphincter
• The SNS is the mechanism for not emptying the
  bladder

197
Levels of Neurogenic Control of Bladder Function
198
Levels of Neurogenic Control of Bladder Function

• Three main levels of neurologic control for
  bladder function
• Spinal cord reflex centers (involuntary/parasympat
  hetic)
• Micturition center in the pons
• Cortical and subcortical centers

(Voluntary Control)
199
Spinal Cord Centers
200
Spinal Cord Centers

• The centers for reflex control of micturition are
  located in S2-S4 (PSNS) and T11-L1 (SNS)
• Afferent (sensory) input from bladder and urethra
  is carried to CNS by fibers that travel with PSNS
  (pelvic), somatic (pudendal), and SNS
  (hypogastric) nerve.

Porth, (2005) Pathophysiology Concepts of
Altered Health States, Lippincott, p. 853.
201
Pelvic Nerves and Muscles
202
Pelvic Nerves and Muscles

• Pelvic nerve carries sensory fibers from stretch
  receptors in bladder wall
• Pudendal nerve carries sensory fibers from the
  external sphincter
• Pelvic muscles and the hypogastric nerve carry
  sensory fibers from the trigone area.

203
Bladder Emptying and Urine StorageDiagram
204
Porth, 2007, Essentials of Pathophysiology, 2nd
ed., Lippincott, p. 578
205
Developmental Micturition
206
Developmental Micturition

• In infants/children micturition is involuntary,
  triggered by spinal cord reflex.
• Bladder fills, detrusor contracts, and internal
  sphincter relaxes.
• As bladder ? in capacity ? ? tone of internal
  sphincter.
• At 2-3 yrs, child becomes conscious of the need
  to urinate and can learn to contract pelvic
  muscles to maintain closure of external sphincter
  and delay urination.
• As nervous system continues to mature, inhibition
  of involuntary detrusor muscle activity takes
  place.
• After child achieves continence, micturition
  becomes voluntary.
• There is a cortical input to the sympathetic
  neurons

207
Disorders in Bladder Function
208
Disorders in Bladder Function

• Urinary tract infection (UTI)
• Urinary obstruction and stasis
• Urinary incontinence
• Neurogenic bladder disorders

209
Urinary Tract Infection (UTI)
210
Urinary Tract Infection (UTI)

• Normally, urine is sterile. An infection occurs
  when bacteria from the stool cling to the opening
  of the urethra and begin to multiply.
• Women, especially young women, have more UTIs
  than men because their urethra is shorter
• Bacteria travel up the urethra and multiply. An
  infection of the urethra is urethritis. A
  bladder infection is called cystitis. If the
  infection is not treated promptly, bacteria may
  then travel further up the ureters to cause a
  kidney infection, called pyelonephritis

211
Structure of the Urinary System and Infection
212
Structure of the Urinary System and Infection

• The urinary system is structured in a way that
  helps ward off infection. The ureters and bladder
  prevent urine from backing up toward the kidneys
  because it is tunneling, and the flow of urine
  from the bladder helps wash bacteria out (as long
  as you void completely).

Porth, 2007, Essentials of Pathophysiology, 2nd
ed., Lippincott, p. 576
213
UTI Symptoms
214
UTI Symptoms

• A frequent urge to urinate with a painful,
  burning in the bladder or urethra during
  urination.
• The urine itself may look milky or cloudy, even
  reddish if blood is present (because the bladder
  is so irritated by the infection).

215
UTI Diagnosis
216
UTI Diagnosis

• Made by urinalysis (U/A)
• The urine is examined for white and red blood
  cells and bacteria.
• A culture may be done to identify the organism.
• E. coli is the most frequent infecting organism

217
UTI Treatment
218
UTI Treatment

• UTIs are treated with antibacterial drugs.
• Drug choice and length of treatment depend on the
  patient history and U/A results.
• The drug most often used to treat routine,
  uncomplicated UTIs is trimethoprim/
  sulfamethoxazole (Bactrim, Septra, Cotrim)
• Often, a UTI can be cured with 1 or 3 days of
  treatment if not complicated by an obstruction or
  other disorder

219
Acquired Urethral Obstruction
220
Acquired Urethral Obstruction

• External compression of urethra caused by benign
  or malignant enlargement of prostate gland
• The prostate becomes larges and can squeeze the
  urethra
• Gonorrhea, STDs ? infection produces urethral
  strictures
• Bladder tumors surround bladder, urethra
• Constipation, fecal impaction

Porth, 2007, Essentials of Pathophysiology, 2nd
ed., Lippincott, p. 580
221
Signs of Outflow Obstruction and Urine Retention
222
Signs of Outflow Obstruction and Urine Retention

• Bladder distention
• Hesitancy
• Straining when initiating urination
• Small and weak stream
• Frequency
• Feeling of incomplete bladder emptying
• Overflow incontinence

223
Urinary Incontinence
224
Urinary Incontinence

• An involuntary loss of urine
• ? Frequency in elderly
• A shorter urethra in women means that there is
  less resistance to flow and incontinence is more
  likely
• Stress incontinence
• Urge incontinence, overactive bladder
• Overflow incontinence
• Mixed (stress and urge)

225
Stress Incontinence
226
Stress Incontinence

• Involuntary loss of urine associated with
  activities, such as coughing
• Associated with activities that increase
  intra-abdominal pressure

227
Overactive Bladder(Urge Incontinence)
228
Overactive Bladder(Urge Incontinence)

• Urgency and frequency associated with activation
  of the detrusor muscle in response to low levels
  of PNS stimulation
• May or may not involve involuntary loss of urine

229
Overflow
230
Overflow

• Involuntary loss of urine when bladder pressure
  is greater than urethral presence in the absence
  of detrusor activity

231
Neurogenic Bladder Disorders
232
Neurogenic Bladder Disorders

• Neural control of bladder function can be
  interrupted at any level (sensory, CNS, or motor)
• Neurogenic disorders
• 1. Failure to store urine spastic bladder
  dysfunction (automatic bladder)
• 2. Failure to empty flaccid bladder dysfunction

233
Neurogenic BladderFailure to Store Urine
234
Neurogenic BladderFailure to Store Urine

• Results from neurogenic lesions above the level
  of the sacral cord (spinal cord injuries or
  stroke) that allow neurons in the micturition
  center in the SC to function reflexively without
  control from higher CNS centers

235
Neurogenic BladderFailure to Empty Bladder
236
Neurogenic BladderFailure to Empty Bladder

• Results from neurologic disorders affecting motor
  neurons in SC or peripheral nerves that control
  detrusor muscle contraction or bladder emptying
• Peripheral neuropathies

237
The micturation center in the brain stem
coordinates the action of the detrusor muscle
and
238
The micturation center in the brain stem
coordinates the action of the detrusor muscle
and

1. External sphincter
2. Conscious control
3. Bladder pressure
4. Neuromediators