1 renal pathophysiology and bladder dysfunction. clinical assessment of renal function 2

Renal Pathophysiology

and Bladder Dysfunction

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

Clearance

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

Volume of urine formed in given time

Conc. of X in systemic blood plasma

Clearance

Conc. of X in urine

Measurement of GFR

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).

GFR = Ux x V

Volume of urine formed in given time

Conc. of X in systemic blood plasma

Glomerular filtration rate

Conc. of X in urine

Metabolism of Blood Urea Nitrogen (BUN)

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

Increased BUN

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

Decreased BUN

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

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.

Serum Creatinine

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

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.

Increased Creatinine

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

Decreased Creatinine

• Elderly

• Persons with small stature, decreased muscle mass

• Inadequate dietary protein

• Muscle atrophy

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

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

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.

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

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

Assessment of Glomerular Function and Integrity

• Proteinuria- protein in the urine

• Types– Transient– Orthostatic– Persistent

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

Orthostatic Proteinuria

• Not associated with deteriorating renal function.

• Increased protein excretion in the upright position and normal protein excretion in the supine position

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)

Types of Dysfunctions that Cause Renal Disease

• First question when you have a patient with renal problems

• Pre-renal

• Intra-renal (Intrinsic)

• Post-renal

Pre-Renal Dysfunction

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

Intra-Renal Dysfunction

• Disorders that disrupt the structures of the kidney

• Causes– Ischemia– Drugs– Glomerular disease– Intratubular obstruction– Toxins from infection

Post-Renal Dysfunction

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

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

• Conditions that cause damage to structures within kidney:– glomeruli, interstitium, tubules

• Injury to tubules most common

• Injury to glomeruli

Intrinsic Causes of Renal DysfunctionInjury to Tubules

• Ischemia

• Toxic insult (drugs)

• Obstruction

Intrinsic Causes of Renal DysfunctionInjury to Glomeruli

• Diabetes– The most common cause of glomerular

disease

• Autoimmune disease

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

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

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

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

IntrinsicGlomerular Disorders

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

• Nephritic syndromes

• Nephrotic syndromes

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

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

Acute Proliferative Glomerulonephritis

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

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.

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

IgA Nephropathy (i.e. Buerger disease)

• Deposition of IgA immune complexes in mesangium

Symptoms of Nephrotic Syndromes

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

• 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)

Diabetic Nephropathy

Hyperglycemia

Hyperfiltration & Hyperperfusion

Microalbuminuria

Afferent arteriole dilation

Increased messangial cell matrixproduction & hypertrophy

GBM thickens

Glomerular sclerosis

Renal Failure

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

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.

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

Intratubular Obstruction

Intratubular Obstruction• Myoglobin

• Hemoglobin

• Large amounts of uric acid or protein

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.

Hemoglobin

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

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)

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

• 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

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

ObstructionDiagram

• 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

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

• Pain– Usually the reason for seeking medical care– Result of distention of bladder, collecting

system, renal capsule.

• Signs of urinary tract infection

Nephrolithiasis

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?

Stones

Stones• Calcium oxalate, calcium

phosphate• Associated with

hypercalcemia– Hyperparathyroidism– Vitamin D intoxication– Diffuse bone disease

• Immobility

• Renal tubular acidosis will favor stone formation

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

Manifestations of Stones• Renal Colic

• Noncolicky Renal Pain

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.

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.

Treatment of Small Stones

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.

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)

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.

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.

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.

Renal Failure

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

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

Acute Renal Failure (ARF)

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

BUN Cr

McCance (2002) Figure 34-6 pg. 1175

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

Causes of Acute Tubular Necrosis

• Ischemia, such as from shock

• Nephrotoxic drugs

• Tubular obstruction• Ex. myoglobin and hemoglobin

• Toxins from infectious agents

Three Phases of ATN

Three Phases of ATN• Onset/initiating

• Maintenance Phase

• Recovery Phase

Onset/Initiating Phase

• Hours/days from onset of insult

• Gradual

• Urine output will decrease slowly

Maintenance Phase

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

Recovery Phase

• Repair of renal tissues

• Gradual improvement in U/O, BUN, and creatinine

Chronic Renal Failure

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

• Diminished Renal Reserve

• Renal Insufficiency

• Renal Failure

• End-Stage Renal Disease (ESRD)

Diminished Renal Reserve

• GFR 50% of normal and BUN/Cr are normal

• No signs/symptoms

Renal Insufficiency

• GFR 20%-50% of normal

• Azotemia

• Anemia

• Hypertension

Renal Failure

• GFR < 20%

• fluid/electrolyte regulation

• Metabolic acidosis

• Other systems fail

End-stage Renal Disease

• GFR < 5% normal

• Atrophy/fibrosis of kidneys

• Dialysis or transplant required

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

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

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

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

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

Consequences of Renal FailureHematologic

• Impaired synthesis of erythropoietin and effects of uremia– Anemia

• Impaired platelet function– Bleeding tendencies

Dialysis

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

The maintenance phase of acute tubular necrosis (ATN) is

characterized by:

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

1. Hypokalemia2. Diuresis3. Edema4. Discolored urine

25% 25%25%25%

Control of Urine Elimination and Disorders

of the Bladder

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

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

Four Layers of Bladder

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

Description of the Bladder

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)

Motor Control of Bladder Function

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

Neural Control of Bladder FunctionNervous System Control

• ANS and Voluntary control

• Parasympathetic Nervous System (PSNS)

• Sympathetic Nervous System (SNS)

Parasympathetic Nervous System

• Excitatory input to the bladder bladder emptying

• Relaxes internal sphincter

• The PNS is the mechanism for emptying the bladder

Sympathetic Nervous System

• Relaxes bladder smooth muscle

• Contracts internal sphincter

• The SNS is the mechanism for not emptying the bladder

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

(Voluntary Control)}

Spinal Cord Centers

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

• 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.

Bladder Emptying and Urine StorageDiagram

204Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 578

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

Disorders in Bladder Function

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

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

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).

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).

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

UTI Treatment

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

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

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

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)

Stress Incontinence

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

abdominal pressure

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

Overflow

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

Neurogenic Bladder Disorders

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

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

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

The micturation center in the brain stem coordinates the action of the

detrusor muscle and:

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

1. External sphincter2. Conscious control3. Bladder pressure4. Neuromediators

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