1 renal pathophysiology and bladder dysfunction. clinical assessment of renal function 2
TRANSCRIPT
1
Renal Pathophysiology
and Bladder Dysfunction
Clinical Assessment of Renal Function
2
3
• Glomerular Filtration Rate– Blood urea nitrogen– Serum creatinine– Creatinine clearance
• Renal Tubular Function and Integrity– Urine Concentrating Ability– Proteinuria– Urinary Sodium Excretion
Clinical Assessment of Renal Function
Clearance
4
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:
Cx = Ux x V
Px
Volume of urine formed in given time
Conc. of X in systemic blood plasma
Clearance
Conc. of X in urine
Measurement of GFR
6
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 Bowman’s capsule per unit time.
• Same equation, GFR is Cx if X has certain required properties (i.e. Ccreatinine).
7
GFR = Ux x V
Px
Volume of urine formed in given time
Conc. of X in systemic blood plasma
Glomerular filtration rate
Conc. of X in urine
Clinical Assessment of Renal Function
Metabolism of Blood Urea Nitrogen (BUN)
8
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
9
Increased BUN
10
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
11
Decreased BUN
12
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
13
BUNBottom Line
14
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.
15
Serum Creatinine
16
Serum Creatinine
• Normal values – Men: 0.8-1.3 mg/dL– Women: 0.6-1.0 mg/dL
17
Creatinine Metabolism
18
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.
19
Increased Creatinine
20
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
21
Decreased Creatinine
22
Decreased Creatinine
• Elderly
• Persons with small stature, decreased muscle mass
• Inadequate dietary protein
• Muscle atrophy
23
Serum CreatinineBottom Line
24
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
25
Creatinine Clearance Test
26
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. 27
Changes in Creatinine Clearance
28
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.
29
Assessment of Renal Tubular Function and Integrity
30
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
31
Factors that Can Influence the Concentration Gradient
32
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
33
Assessment of Glomerular Function and Integrity
34
Assessment of Glomerular Function and Integrity
• Proteinuria- protein in the urine
• Types– Transient– Orthostatic– Persistent
35
Transient Proteinuria
36
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
37
Orthostatic Proteinuria
38
Orthostatic Proteinuria
• Not associated with deteriorating renal function.
• Increased protein excretion in the upright position and normal protein excretion in the supine position
39
Persistent Proteinuria
40
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)
41
Types of Dysfunctions that Cause Renal Disease
42
Types of Dysfunctions that Cause Renal Disease
• First question when you have a patient with renal problems
• Pre-renal
• Intra-renal (Intrinsic)
• Post-renal
43
Pre-Renal Dysfunction
44
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
45
Intra-Renal Dysfunction
46
Intra-Renal Dysfunction
• Disorders that disrupt the structures of the kidney
• Causes– Ischemia– Drugs– Glomerular disease– Intratubular obstruction– Toxins from infection
47
Post-Renal Dysfunction
48
Post-Renal Dysfunction
• Disorders that impair urine outflow from the kidneys– Ureteral obstruction– Obstruction of the ureters or the urethra
49
Pre-renal Causes of Kidney Dysfunction
50
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 51
Intrinsic Causes of Renal Dysfunction
52
Intrinsic Causes of Renal Dysfunction
• Conditions that cause damage to structures within kidney:– glomeruli, interstitium, tubules
• Injury to tubules most common
• Injury to glomeruli
53
Intrinsic Causes of Renal DysfunctionInjury to Tubules
54
Intrinsic Causes of Renal DysfunctionInjury to Tubules
• Ischemia
• Toxic insult (drugs)
• Obstruction
55
Intrinsic Causes of Renal DysfunctionInjury to Glomeruli
56
Intrinsic Causes of Renal DysfunctionInjury to Glomeruli
• Diabetes– The most common cause of glomerular
disease
• Autoimmune disease
57
Immune Mechanisms of Glomerular Disease
58
Immune Mechanisms of Glomerular Disease
59
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
Anti-Glomerular Membrane Antibodies
60
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
61
Circulating Antigen-Antibody Complex Deposition
62
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
63
End Result of the Immune Mechanisms of Glomerular Disease
64
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
65
IntrinsicGlomerular Disorders
66
IntrinsicGlomerular Disorders
• Glomerular disorders affect glomerular capillary structures that filter material from the blood.
• Nephritic syndromes
• Nephrotic syndromes
67
Nephritic Syndromes
68
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
69
Nephrotic Syndromes
70
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
71
Acute Proliferative Glomerulonephritis
72
Acute Proliferative Glomerulonephritis
73
Infection withstreptococci
Immune complexes/antigens glom onto the strep, creating circulating
complexes that become entrapped in the glomerular
membrane
Activation of complementRecruitment of
leukocytes
Inflammation and SwellingOf capillary membrane
GBM damage
HematuriaProteinuriaRBC Casts – shape of the tubule because so many rbcs were in the tubule nephrotic syndrome
Blockage of RenalCapillaries and GFR
Oliguria,Na+ and H2O retentionHypervolemia nephritic syndrome
EdemaHypertension, HFEncephalopathyRenal Failure
Proliferation ofMC & EC
Other Nephritic Syndromes
74
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.
75
Rapidly Progressive Glomerulonephritis
76
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
77
IgA Nephropathy (i.e. Buerger disease)
78
IgA Nephropathy (i.e. Buerger disease)
• Deposition of IgA immune complexes in mesangium
79
Symptoms of Nephrotic Syndromes
80
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 capillary81
Nephrotic Disorders
82
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)
83
Diabetic Nephropathy
84
Diabetic Nephropathy
85
Hyperglycemia
MAP
Hyperfiltration & Hyperperfusion
Microalbuminuria
Afferent arteriole dilation
Pc
Increased messangial cell matrixproduction & hypertrophy
GFR
GBM thickens
Glomerular sclerosis
Renal Failure
GFR
Diabetic NephropathyDescription
86
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
87
Hypertensive Glomerular Disease
88
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.
89
Hypertension and the Kidneys
90
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
91
Intratubular Obstruction
92
Intratubular Obstruction• Myoglobin
• Hemoglobin
• Large amounts of uric acid or protein
93
Myoglobin
94
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.
95
Hemoglobin
96
Hemoglobin
• Hemolysis, including blood transfusion reactions, liberates the hemoglobin and causes tubular obstruction
97
Large Amounts of Uric Acid or Protein
98
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)
99
Postrenal Causes of Renal Failure
100
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
101Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 540
Mechanisms of Renal Damage Due to Obstruction
102
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
103
Most Damaging Effects of Obstruction
104
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
105
ObstructionDiagram
106
• 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
107
Hydronephrosis is distention (dilation) of the kidney with urine, caused by backward pressure on the kidney when the flow of urine is obstructed.
•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.
Description By:H. Yamase, M.D. (Image Contrib. by: UCHC
)
Merck Manual
Manifestations of Obstruction
108
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
109
Nephrolithiasis
110
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?
111
Stones
112
Stones• Calcium oxalate, calcium
phosphate• Associated with
hypercalcemia– Hyperparathyroidism– Vitamin D intoxication– Diffuse bone disease
• Immobility
• Renal tubular acidosis will favor stone formation
113
A 58-year-old man presented with a 1 year history of dysuria
114
A 58-year-old man presented with a 1 year history of dysuria
115Rajaian S and Kekre N. N Engl J Med 2009;361:1486
Rajaian S and Kekre N. N Engl J Med 2009;361:1486
Manifestations of Stones
116
Manifestations of Stones• Renal Colic
• Noncolicky Renal Pain
117
Renal Colic
118
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.
119
Noncolicky Renal Pain
120
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.
121
Treatment of Small Stones
122
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.
123
Treatment of Larger Renal Stones
124
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)
125
Extracorporeal Shock Wave Lithotripsy (ESWL)
126
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.
127
Ureteroscopic Stone Removal
128
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.
129
Percutaneous Nephrolithotomy (PCNL)
130
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.
131
Renal Failure
132
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
133
Types of Renal Failure
134
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
135
Acute Renal Failure (ARF)
136
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
137
BUN Cr
GFR
McCance (2002) Figure 34-6 pg. 1175
Acute Tubular Necrosis (ATN)
138
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
139
Causes of Acute Tubular Necrosis
140
Causes of Acute Tubular Necrosis
• Ischemia, such as from shock
• Nephrotoxic drugs
• Tubular obstruction• Ex. myoglobin and hemoglobin
• Toxins from infectious agents
141
Three Phases of ATN
142
Three Phases of ATN• Onset/initiating
• Maintenance Phase
• Recovery Phase
143
Onset/Initiating Phase
144
Onset/Initiating Phase
• Hours/days from onset of insult
• Gradual
• Urine output will decrease slowly
145
Maintenance Phase
146
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
147
Recovery Phase
148
Recovery Phase
• Repair of renal tissues
• Gradual improvement in U/O, BUN, and creatinine
149
Chronic Renal Failure
150
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.
151Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p.564
Chronic Renal FailureStages of Progression
152
Chronic Renal FailureStages of Progression
• Diminished Renal Reserve
• Renal Insufficiency
• Renal Failure
• End-Stage Renal Disease (ESRD)
153
Diminished Renal Reserve
154
Diminished Renal Reserve
• GFR 50% of normal and BUN/Cr are normal
• No signs/symptoms
155
Renal Insufficiency
156
Renal Insufficiency
• GFR 20%-50% of normal
• Azotemia
• Anemia
• Hypertension
157
Renal Failure
158
Renal Failure
• GFR < 20%
• fluid/electrolyte regulation
• Metabolic acidosis
• Other systems fail
159
End-stage Renal Disease
160
End-stage Renal Disease
• GFR < 5% normal
• Atrophy/fibrosis of kidneys
• Dialysis or transplant required
161
Signs and Symptoms of Renal Failure
162
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
163
Signs/Symptoms of Renal FailureFluid and Electrolyte Imbalance
164
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 165
Signs/Symptoms of Renal FailureAnemia, Hyperparathyroidism, High
Concentrations
166
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
167
Consequences of Renal FailureCardiovascular
168
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
169
Consequences of Renal FailureBody Fluids
170
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
171
Consequences of Renal FailureHematologic
172
Consequences of Renal FailureHematologic
• Impaired synthesis of erythropoietin and effects of uremia– Anemia
• Impaired platelet function– Bleeding tendencies
173
Dialysis
174
Dialysis
175
Renal Failure and the Elimination of Drugs
176
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
177
The maintenance phase of acute tubular necrosis (ATN) is
characterized by:
178
The maintenance phase of acute tubular necrosis (ATN) is characterized by:
1. Hypokalemia2. Diuresis3. Edema4. Discolored urine
179
25% 25%25%25%
Control of Urine Elimination and Disorders
of the Bladder
180
Control of Urine Elimination
181
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
182
Alterations in Urine Elimination
183
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
184
Four Layers of Bladder
185
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
186
Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 576
Description of the Bladder
187
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)
188
Motor Control of Bladder Function
189
Motor Control of Bladder Function• Detrusor muscle
– Muscle of micturition (smooth muscle)– Contractsurine 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
190
Neural Control of Bladder FunctionNervous System Control
191
Neural Control of Bladder FunctionNervous System Control
• ANS and Voluntary control
• Parasympathetic Nervous System (PSNS)
• Sympathetic Nervous System (SNS)
192
Parasympathetic Nervous System
193
Parasympathetic Nervous System
• Excitatory input to the bladder bladder emptying
• Relaxes internal sphincter
• The PNS is the mechanism for emptying the bladder
194
Sympathetic Nervous System
195
Sympathetic Nervous System
• Relaxes bladder smooth muscle
• Contracts internal sphincter
• The SNS is the mechanism for not emptying the bladder
196
Levels of Neurogenic Control of Bladder Function
197
Levels of Neurogenic Control of Bladder Function
• Three main levels of neurologic control for bladder function– Spinal cord reflex centers
(involuntary/parasympathetic)– Micturition center in the pons– Cortical and subcortical centers
198
(Voluntary Control)}
Spinal Cord Centers
199
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.
200Porth, (2005) Pathophysiology: Concepts of Altered Health States, Lippincott, p. 853.
Pelvic Nerves and Muscles
201
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.
202
Bladder Emptying and Urine StorageDiagram
203
204Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 578
Developmental Micturition
205
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
206
Disorders in Bladder Function
207
Disorders in Bladder Function
• Urinary tract infection (UTI)• Urinary obstruction and stasis• Urinary incontinence• Neurogenic bladder disorders
208
Urinary Tract Infection (UTI)
209
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
210
Structure of the Urinary System and Infection
211
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).
212
Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 576
UTI Symptoms
213
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).
214
UTI Diagnosis
215
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
216
UTI Treatment
217
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
218
Acquired Urethral Obstruction
219
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
220
Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 580
Signs of Outflow Obstruction and Urine Retention
221
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
222
Urinary Incontinence
223
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)
224
Stress Incontinence
225
Stress Incontinence
• Involuntary loss of urine associated with activities, such as coughing– Associated with activities that increase intra-
abdominal pressure
226
Overactive Bladder(Urge Incontinence)
227
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
228
Overflow
229
Overflow
• Involuntary loss of urine when bladder pressure is greater than urethral presence in the absence of detrusor activity
230
Neurogenic Bladder Disorders
231
Neurogenic Bladder Disorders• Neural control of bladder function can be interrupted at
any level (sensory, CNS, or motor)
• Neurogenic disorders1. Failure to store urine = spastic bladder dysfunction (automatic
bladder)
2. Failure to empty = flaccid bladder dysfunction
232
Neurogenic BladderFailure to Store Urine
233
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
234
Neurogenic BladderFailure to Empty Bladder
235
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
236
The micturation center in the brain stem coordinates the action of the
detrusor muscle and:
237
The micturation center in the brain stem coordinates the action of the detrusor muscle and:
1. External sphincter2. Conscious control3. Bladder pressure4. Neuromediators
238
25% 25%25%25%