Genitourinary Pathophysiology Randall L. Tackett, Ph.D

Genitourinary PathophysiologyGenitourinary Pathophysiology

Randall L. Tackett, Ph.D.Randall L. Tackett, Ph.D.

OverviewOverview

• Anatomy and functions of the systemAnatomy and functions of the system

• NephronNephron

• Homestatic functionsHomestatic functions

• Tests of renal functionTests of renal function

• Effects of agingEffects of aging

• Renal failureRenal failure

• UTIsUTIs

Anatomy of Renal and Urologic SystemAnatomy of Renal and Urologic System

Figure 34-1Figure 34-1

Functions of the KidneyFunctions of the Kidney

• Balance solute and water transportBalance solute and water transport

• Excretion of metabolic waste productsExcretion of metabolic waste products

• Conserve nutrientsConserve nutrients

• Regulation of acid and base balanceRegulation of acid and base balance

Endocrine Functions of KidneyEndocrine Functions of Kidney

• Renin – Blood pressure and fluid Renin – Blood pressure and fluid regulationregulation

• Erythropoietin – RBC productionErythropoietin – RBC production

• 1,25-dihydroxyvitamin D1,25-dihydroxyvitamin D33 – Calcium – Calcium

• Gluconeogenesis Gluconeogenesis – Severe fastingSevere fasting– From amino acidsFrom amino acids

NephronNephron

• Functional unit of the kidneyFunctional unit of the kidney

• Approximately 1.2 million nephrons in Approximately 1.2 million nephrons in each kidneyeach kidney

• Multicomponent tubular structure lined Multicomponent tubular structure lined by epithelial cellsby epithelial cells– Formation of urineFormation of urine– Secretion/reabsorptionSecretion/reabsorption

GlomerulusGlomerulus

• Tuft of capillaries contained in Tuft of capillaries contained in Bowman’s capsuleBowman’s capsule

• Main site where filtration of blood occursMain site where filtration of blood occurs

• All components of blood are filtered All components of blood are filtered except:except:– Blood cellsBlood cells– Plasma proteins with MW > 70,000Plasma proteins with MW > 70,000

Juxtaglomerular ApparatusJuxtaglomerular Apparatus

• Composed ofComposed of– Juxtaglomerular cells (renin)Juxtaglomerular cells (renin)– Macula densa (sodium)Macula densa (sodium)

• ControlsControls– Renal blood flowRenal blood flow– GFRGFR– Renin secretionRenin secretion

Figure 34-3Figure 34-3

Components of the NephronComponents of the Nephron

Renal Blood FlowRenal Blood Flow

• Kidneys receive 20% to 25% of COKidneys receive 20% to 25% of CO• Glomerular filtration rate (GFR)Glomerular filtration rate (GFR)

– Filtration of plasma/unit of timeFiltration of plasma/unit of time– GFR is directly related to renal blood flowGFR is directly related to renal blood flow

• Between arterial pressures of 80-180 Between arterial pressures of 80-180 mmHg, local mechanisms mmHg, local mechanisms (autoregulation) renal blood flow and (autoregulation) renal blood flow and thus, GFR constantthus, GFR constant

Control of Renal Blood FlowControl of Renal Blood Flow

• AutoregulationAutoregulation– Myogenic mechanismMyogenic mechanism– Tubuloglomerular feedbackTubuloglomerular feedback

• Neural regulationNeural regulation

• Renin-AII systemRenin-AII system

• Atrial natriuretic peptideAtrial natriuretic peptide

Stimulants of the Renin-AII SystemStimulants of the Renin-AII System

• Reduced blood pressureReduced blood pressure

• Decreased sodium concentration in distal Decreased sodium concentration in distal tubuletubule

• SNS stimulationSNS stimulation

Renin-AII SystemRenin-AII System

Figure 28-33

Nephron FunctionNephron Function

• Major function is to form a filtrate of Major function is to form a filtrate of protein-free plasma (ultrafiltration)protein-free plasma (ultrafiltration)

• Regulates filtrate to maintainRegulates filtrate to maintain– Body fluid volumeBody fluid volume– Electrolyte compositionElectrolyte composition– pHpH

Regulation of FiltrateRegulation of Filtrate

• Tubular reabsorptionTubular reabsorption

• Tubular secretionTubular secretion

Glomerular Filtrate CompositionGlomerular Filtrate Composition

• Protein-freeProtein-free

• ElectrolytesElectrolytes

• Organic moleculesOrganic molecules– GlucoseGlucose– CreatinineCreatinine– UreaUrea

Glomerular FiltrationGlomerular Filtration

Permeability of substances crossing the Permeability of substances crossing the glomerulus is determined by:glomerulus is determined by:

• Molecular sizeMolecular size

• Electrical chargeElectrical charge

Major Function of Nephron SegmentsMajor Function of Nephron Segments

Figure 34-11

Concentration/Dilution of UrineConcentration/Dilution of Urine

• Involves a countercurrent exchange mechanismInvolves a countercurrent exchange mechanism– Fluid flows in opposite directions through parallel Fluid flows in opposite directions through parallel

tubestubes

– Concentration gradient causes fluid to be exchanged Concentration gradient causes fluid to be exchanged across parallel pathwaysacross parallel pathways

• The longer the tube the greater the The longer the tube the greater the concentration gradientconcentration gradient

• Loop of Henle serves as the multiplier of the Loop of Henle serves as the multiplier of the concentration gradientconcentration gradient


• Efficiency of water conservation is related to Efficiency of water conservation is related to length of loops of Henlelength of loops of Henle– Longer the loops, the greater the ability to Longer the loops, the greater the ability to

concentrate urineconcentrate urine

• UreaUrea– Product of protein metabolismProduct of protein metabolism

– One of the major constituents of urineOne of the major constituents of urine

– Approximately 50% is excreted, 50% is recycledApproximately 50% is excreted, 50% is recycled

– Contributes to osmotic gradient in kidneyContributes to osmotic gradient in kidney


• Antidiuretic hormoneAntidiuretic hormone– Controls final concentration of urineControls final concentration of urine– Secreted from the posterior pituitarySecreted from the posterior pituitary– Increases water permeability of distal tubule Increases water permeability of distal tubule

and the collecting ductsand the collecting ducts– Can be a cause of oliguriaCan be a cause of oliguria

Acid-Base BalanceAcid-Base Balance

• Distal tubule of kidney regulates acid-Distal tubule of kidney regulates acid-base balancebase balance– Secretes hydrogen into tubuleSecretes hydrogen into tubule– Reabsorbs bicarbonateReabsorbs bicarbonate

• Buffers in tubular fluid combine with Buffers in tubular fluid combine with hydrogen ion, allowing more hydrogen hydrogen ion, allowing more hydrogen ion to be excretedion to be excreted


• Phosphate and ammonia represent Phosphate and ammonia represent important renal buffersimportant renal buffers– Phosphate is filtered at glomerulusPhosphate is filtered at glomerulus– 75% is reabsorbed, remainder is available as 75% is reabsorbed, remainder is available as

a renal buffera renal buffer

• Hydrogen ion combines with phosphate Hydrogen ion combines with phosphate to form a negatively charged molecule to form a negatively charged molecule which makes it lipid insolublewhich makes it lipid insoluble


• Ammonia is not ionized and is lipid Ammonia is not ionized and is lipid solublesoluble

• Ammonia creates a concentration Ammonia creates a concentration gradientgradient– Diffuses into renal tubular fluid to combine Diffuses into renal tubular fluid to combine

with hydrogen to form ammonium ion with hydrogen to form ammonium ion – Ammonium is eliminated in urineAmmonium is eliminated in urine


• Renal buffering also requires CORenal buffering also requires CO22

• Carbonic anhydrase catalyzes the formation of Carbonic anhydrase catalyzes the formation of hydrogen ion and bicarbonate ionhydrogen ion and bicarbonate ion

• Hydrogen is secreted from tubular cell and Hydrogen is secreted from tubular cell and buffered in the lumen by ammonia and buffered in the lumen by ammonia and phosphatephosphate

• Bicarbonate is generated which contributes to Bicarbonate is generated which contributes to plasma alkalinityplasma alkalinity

• Hydrogen is excreted in urineHydrogen is excreted in urine

Renal Function and AgingRenal Function and Aging

• Linear decrease in renal blood flowLinear decrease in renal blood flow– Due to change in renal vasculature and Due to change in renal vasculature and

perfusionperfusion– Reduction in numbers of nephronsReduction in numbers of nephrons

• Nephron loss accelerates between 40 and Nephron loss accelerates between 40 and 80 yrs of age80 yrs of age

• By 75 yrs of age, functional nephrons are By 75 yrs of age, functional nephrons are reduced 30% to 50%reduced 30% to 50%


• Decreased ability to concentrate urineDecreased ability to concentrate urine

• Reabsorption of glucose, bicarbonate and Reabsorption of glucose, bicarbonate and sodium is less efficientsodium is less efficient

• Age-related decline in renal activation of Age-related decline in renal activation of vitamin D decreases calcium absorption vitamin D decreases calcium absorption in the intestinesin the intestines


• Response to acid or base load is delayed Response to acid or base load is delayed and prolongedand prolonged

• Alteration of drug responseAlteration of drug response

Tests of Renal FunctionTests of Renal Function

• ClearanceClearance

• Plasma creatinine concentrationPlasma creatinine concentration

• Blood urea nitrogen (BUN)Blood urea nitrogen (BUN)

• UrinalysisUrinalysis

Renal ClearanceRenal Clearance

• Determines the amount of a substance Determines the amount of a substance cleared from the blood by the kidneys cleared from the blood by the kidneys per unit of timeper unit of time

• Permits an indirect measure of:Permits an indirect measure of:– GFRGFR– Tubular secretionTubular secretion– Tubular reabsorptionTubular reabsorption– Renal blood flowRenal blood flow

Clearance and GFRClearance and GFR

• GFR provides best estimate of functional GFR provides best estimate of functional renal tissuerenal tissue

• Criteria for test substance to measure Criteria for test substance to measure GFR:GFR:– Stable plasma concentrationStable plasma concentration– Freely filtered at glomerulusFreely filtered at glomerulus– Not secreted, reabsorbed or metabolized by Not secreted, reabsorbed or metabolized by

the tubulesthe tubules


• Inulin (a fructose polysaccharide) meets Inulin (a fructose polysaccharide) meets these criteria and is used to evaluate these criteria and is used to evaluate GFRGFR

• GFR can be calculated by:GFR can be calculated by:

GFR (ml/min) = GFR (ml/min) = UUinulininulin x Volume x Volume

PPinulininulin


• Use of inulin requires constant infusion Use of inulin requires constant infusion to maintain stable plasma levelto maintain stable plasma level

• An alternative to inulin is creatinineAn alternative to inulin is creatinine– Produced by muscleProduced by muscle– Released into blood at a relatively constant Released into blood at a relatively constant

raterate– Freely filtered at glomerulus but small Freely filtered at glomerulus but small

amount is secreted by tubules (leads to amount is secreted by tubules (leads to overestimation of GFR)overestimation of GFR)


• Overestimation of GFR with creatinine is Overestimation of GFR with creatinine is within tolerable limitswithin tolerable limits

• Only one blood sample required with Only one blood sample required with creatinine plus a 24 hr urinecreatinine plus a 24 hr urine

Clearance and Renal Blood FlowClearance and Renal Blood Flow

• Renal plasma and blood flow can be Renal plasma and blood flow can be estimated using para-aminohippurate estimated using para-aminohippurate (PAH)(PAH)

• PAH is filtered at the glomerulus and the PAH is filtered at the glomerulus and the remainder is secreted into the tubules in remainder is secreted into the tubules in one circulation through the kidneysone circulation through the kidneys

Plasma Creatinine ConcentrationPlasma Creatinine Concentration

• Plasma creatinine is stable when GFR is stablePlasma creatinine is stable when GFR is stable• Creatinine produced at a constant rate as a Creatinine produced at a constant rate as a

product of muscle metabolismproduct of muscle metabolism• When GFR decreases, plasma creatinine When GFR decreases, plasma creatinine

increases proportionatelyincreases proportionately• More important for monitoring chronic renal More important for monitoring chronic renal

failure – plasma creatinine requires 7-10 days failure – plasma creatinine requires 7-10 days to stabilize when GFR declinesto stabilize when GFR declines

Blood Urea Nitrogen (BUN)Blood Urea Nitrogen (BUN)

• BUN reflects– GFR– Urine concentrating capacity

• BUN increases as GFR decreases but varies with altered protein intake

• BUN increases in states of dehydration and renal failure

UrinalysisUrinalysis

• Non-invasive and economicalNon-invasive and economical• EvaluatesEvaluates

– ColorColor

– TurbidityTurbidity

– ProteinProtein

– pHpH

– Specific gravitySpecific gravity

– SedimentSediment

– SupernatantSupernatant


• Turbidity increases when formed Turbidity increases when formed substances (crystals, cells, casts) are substances (crystals, cells, casts) are presentpresent

• Foaming is the result of protein or bile Foaming is the result of protein or bile pigmentspigments

• pHpH– Alkaline after mealsAlkaline after meals– Acidic upon awakeningAcidic upon awakening


• Specific gravity is the estimated solute Specific gravity is the estimated solute concentration in the urineconcentration in the urine– Can be affected by state of hydrationCan be affected by state of hydration

• Urine sediment – microscopic examUrine sediment – microscopic exam– Cells, casts, crystals, bacteriaCells, casts, crystals, bacteria

• RBCsRBCs


• Casts (cellular precipitates)Casts (cellular precipitates)– Red cell casts suggest bleedingRed cell casts suggest bleeding– White cell casts suggest inflammationWhite cell casts suggest inflammation– Epithelial casts indicate tubular Epithelial casts indicate tubular

degeneration or necrosisdegeneration or necrosis

• CrystalsCrystals– Can indicate inflammation, infection or Can indicate inflammation, infection or

metabolic disordermetabolic disorder


• WBCsWBCs– PyuriaPyuria– Indicative of UTIIndicative of UTI

• Other measures (dipstick tests)Other measures (dipstick tests)– GlucoseGlucose– BilirubinBilirubin– HemoglobinHemoglobin

• DrugsDrugs

Renal FailureRenal Failure

• Renal insufficiencyRenal insufficiency– GFR approximately 25% of normalGFR approximately 25% of normal– Serum creatinine and urea mildly elevatedSerum creatinine and urea mildly elevated

• Renal FailureRenal Failure– Significant loss of renal functionSignificant loss of renal function

• End-stage renal failure End-stage renal failure – Less than 10% of renal functionLess than 10% of renal function

Renal FailureRenal Failure

• Can be acute or chronicCan be acute or chronic

• Reversible or irreversibleReversible or irreversible

• Rapid or slow progressionRapid or slow progression

UremiaUremia

• Syndrome of renal failureSyndrome of renal failure

• Elevated blood urea and creatinine levelsElevated blood urea and creatinine levels

• Represents consequences of renal failureRepresents consequences of renal failure– Retention of toxins and wastesRetention of toxins and wastes– Deficiency statesDeficiency states– Electrolyte disturbancesElectrolyte disturbances

AzotemiaAzotemia

• Refers to increased serum urea levelsRefers to increased serum urea levels

• Creatinine serum levels are often also Creatinine serum levels are often also increasedincreased

• Caused by renal insufficiency or failureCaused by renal insufficiency or failure

Azotemia vs UremiaAzotemia vs Uremia

• Often incorrectly used interchangablyOften incorrectly used interchangably

• Both terms represent the accumulation of Both terms represent the accumulation of nitrogenous waste products in the bloodnitrogenous waste products in the blood

Acute Renal Failure (ARF)Acute Renal Failure (ARF)

• Abrupt reduction in renal function with Abrupt reduction in renal function with elevated BUN and plasma creatinineelevated BUN and plasma creatinine

• Usually, but not always, associated with Usually, but not always, associated with oliguriaoliguria– Urine output less than 30 ml/hr or 400 ml/dUrine output less than 30 ml/hr or 400 ml/d

• Usually reversible if diagnosed and Usually reversible if diagnosed and treated early after onsettreated early after onset

Classification of ARFClassification of ARF

• Prerenal Prerenal

• IntrarenalIntrarenal

• PostrenalPostrenal

Classification of ARF

Table 35-9

ARF: Clinical ManifestationsARF: Clinical Manifestations

Clinical progression occurs in three Clinical progression occurs in three phases:phases:

1.1. OliguriaOliguria

2.2. DiuresisDiuresis

3.3. RecoveryRecovery

ARF: OliguriaARF: Oliguria

• Begins within 1 day Begins within 1 day • Can last from 1-3 weeks depending on Can last from 1-3 weeks depending on

severity of insultseverity of insult• Anuria is uncommonAnuria is uncommon• 10%-20% of patients have nonoliguric 10%-20% of patients have nonoliguric

failurefailure• Urine output may vary but BUN and Urine output may vary but BUN and

plasma creatinine increaseplasma creatinine increase

Mechanisms of OliguriaMechanisms of Oliguria

Figure 35-11

ARF: DiuresisARF: Diuresis

• Renal function begins to recoverRenal function begins to recover

• Diuresis is progressiveDiuresis is progressive

• Tubules are still damagedTubules are still damaged– Sodium and potassium are lost in urineSodium and potassium are lost in urine– Risk for hypokalemiaRisk for hypokalemia– Volume depletion (3-4 L/d) may occurVolume depletion (3-4 L/d) may occur

ARF: RecoveryARF: Recovery

• Plasma creatinine provides an index of Plasma creatinine provides an index of renal functionrenal function

• Return to normal may take 3-12 monthsReturn to normal may take 3-12 months

• Approximately one-third of patients do Approximately one-third of patients do not have full recovery of normal GFR or not have full recovery of normal GFR or tubular functiontubular function

Chronic Renal FailureChronic Renal Failure

• Symptomatic changes usually do not Symptomatic changes usually do not become evident until renal function become evident until renal function declines to less than 25% of normaldeclines to less than 25% of normal

• Proposed theories of the adaptive Proposed theories of the adaptive response response – Location of damageLocation of damage– Intact nephronIntact nephron– Hyperfiltration Hyperfiltration

Location of DamageLocation of Damage

• Location of damage predicts symptomsLocation of damage predicts symptoms• Tubular interstitial disease damages tubular or Tubular interstitial disease damages tubular or

medullary portions of the nephron resulting in:medullary portions of the nephron resulting in:– Renal tubular acidosisRenal tubular acidosis– Sodium wastingSodium wasting– Difficulty in concentrating/diluting urineDifficulty in concentrating/diluting urine

• Vascular or glomerular damage results in:Vascular or glomerular damage results in:– ProteinuriaProteinuria– HematuriaHematuria

Intact Nephron TheoryIntact Nephron Theory

• Loss of nephron mass causes remaining Loss of nephron mass causes remaining nephrons to increase functionnephrons to increase function

• Constant rate of excretion is maintained Constant rate of excretion is maintained in the presence of declining GFRin the presence of declining GFR– Major end products in urine are similar to Major end products in urine are similar to

that in normal patientsthat in normal patients– Abnormal amounts of protein, RBCs, white Abnormal amounts of protein, RBCs, white

blood cells and castsblood cells and casts

Hyperfiltration TheoryHyperfiltration Theory

• Continued long-term exposure to Continued long-term exposure to increased capillary pressure and flow increased capillary pressure and flow results in progressive failure of intact results in progressive failure of intact nephronsnephrons

• Loss of GFRLoss of GFR

Factors Contributing to the Factors Contributing to the Pathophysiology of Renal FailurePathophysiology of Renal Failure

• Creatinine and urea clearanceCreatinine and urea clearance

• Sodium and water balanceSodium and water balance

• Phosphate and calcium balancePhosphate and calcium balance

• HematocritHematocrit

• Potassium balancePotassium balance

• Acid-base balanceAcid-base balance

Creatinine and UreaCreatinine and Urea

• Creatinine is constantly released from muscle Creatinine is constantly released from muscle and excreted by glomerular filtrationand excreted by glomerular filtration

• Amount of creatinine produced equals the Amount of creatinine produced equals the amount filtered and excretedamount filtered and excreted

• If GFR falls, plasma creatinine level increasesIf GFR falls, plasma creatinine level increases• This relationship allows plasma creatinine This relationship allows plasma creatinine

concentration to serve as an index of concentration to serve as an index of glomerular functionglomerular function

Creatinine and UreaCreatinine and Urea

• Clearance of urea is similar to that of Clearance of urea is similar to that of creatinine creatinine exceptexcept::– Urea is filtered and reabsorbedUrea is filtered and reabsorbed– Urea varies with state of hydration and dietUrea varies with state of hydration and diet

• If protein intake and metabolism are If protein intake and metabolism are constant, plasma levels of urea increase constant, plasma levels of urea increase as GFR decreasesas GFR decreases

Sodium and Water BalanceSodium and Water Balance

• Sodium levels must be regulated within Sodium levels must be regulated within narrow limitsnarrow limits

• In chronic renal failure, sodium load In chronic renal failure, sodium load delivered to remaining nephrons is delivered to remaining nephrons is greater than normalgreater than normal

• Increased excretion is accomplished by Increased excretion is accomplished by decreased reabsorptiondecreased reabsorption


• Nephron has difficulty conserving Nephron has difficulty conserving sodium when GFR decreases below 25%sodium when GFR decreases below 25%– Obligatory loss of 20-40 mEq of sodium per Obligatory loss of 20-40 mEq of sodium per

day occursday occurs

• If dietary intake is less than above, If dietary intake is less than above, sodium deficits and volume depletion sodium deficits and volume depletion occursoccurs

• Loss of urea can induce osmotic diuresisLoss of urea can induce osmotic diuresis


• As GFR is reduced, the ability to As GFR is reduced, the ability to concentrate and dilute urine is lostconcentrate and dilute urine is lost

• Individual nephrons can maintain water Individual nephrons can maintain water balance until GFR declines to 15% to balance until GFR declines to 15% to 20% of normal20% of normal

PotassiumPotassium

• Excretion is related primarily to distal Excretion is related primarily to distal tubular secretion and is mediated by:tubular secretion and is mediated by:– AldosteroneAldosterone– Na/K ATPaseNa/K ATPase

• Tubular secretion increases until oliguria Tubular secretion increases until oliguria occursoccurs

• Large losses of potassium can occur Large losses of potassium can occur through the bowelthrough the bowel

PotassiumPotassium

• Once oliguric, patients are very prone to Once oliguric, patients are very prone to hyperkalemia especially with:hyperkalemia especially with:– Salt substitutesSalt substitutes– Potassium-sparing diureticsPotassium-sparing diuretics– Volume depletionVolume depletion

• At end-stage renal failure, total body At end-stage renal failure, total body potassium can increase and become life potassium can increase and become life threateningthreatening


• Intake of normal diet produces 50 to 100 Intake of normal diet produces 50 to 100 mEq of hydrogen per daymEq of hydrogen per day

• Hydrogen is normally excreted in urine Hydrogen is normally excreted in urine and combined with phosphate and and combined with phosphate and ammoniaammonia

• In early failure, pH is maintained by an In early failure, pH is maintained by an increased rate of acid excretion and increased rate of acid excretion and bicarbonate reabsorptionbicarbonate reabsorption


• Metabolic acidosis begins to occur when GFR Metabolic acidosis begins to occur when GFR decreases by 30% to 40% due to:decreases by 30% to 40% due to:– Decreased ammonia synthesisDecreased ammonia synthesis– Decreased bicarbonate reabsorptionDecreased bicarbonate reabsorption

• Phosphate buffers remain effective until late Phosphate buffers remain effective until late stages of failurestages of failure

• Bicarbonate levels stabilize at end-stage failure Bicarbonate levels stabilize at end-stage failure because hydrogen is buffered by anions from because hydrogen is buffered by anions from bonebone

Phosphate and Calcium BalancePhosphate and Calcium Balance

• Changes in acid-base balance affect Changes in acid-base balance affect phosphate and calciumphosphate and calcium

• In early failure, phosphate excretion In early failure, phosphate excretion decreases and plasma phosphate levels decreases and plasma phosphate levels increase due to decreased GFRincrease due to decreased GFR

• Elevated plasma phosphate binds Elevated plasma phosphate binds calcium producing hypocalcemiacalcium producing hypocalcemia


• Decreased calcium stimulates the release Decreased calcium stimulates the release of parathyroid hormone which releases of parathyroid hormone which releases calcium from bone and enhances urinary calcium from bone and enhances urinary phosphate secretionphosphate secretion

• Phosphate and calcium levels return to Phosphate and calcium levels return to normalnormal

• Incremental losses of GFR decreases Incremental losses of GFR decreases effectiveness of parathyroid hormoneeffectiveness of parathyroid hormone


• When GFR declines to 25% of normal, When GFR declines to 25% of normal, parathyroid hormone is no longer parathyroid hormone is no longer effective in maintaining serum phosphateeffective in maintaining serum phosphate

• Persistent reduction of GFR and Persistent reduction of GFR and hyperparathyroidism results in:hyperparathyroidism results in:– HyperphosphatemiaHyperphosphatemia– HypocalcemiaHypocalcemia– Dissolution of boneDissolution of bone


Hypocalcemia and bone disease are Hypocalcemia and bone disease are accelerated by:accelerated by:

• Impaired synthesis of 1,25 vitamin DImpaired synthesis of 1,25 vitamin D33

• Lack of vitamin D reduces intestinal Lack of vitamin D reduces intestinal absorption of calcium and impairs absorption of calcium and impairs resorption of phosphate and calcium resorption of phosphate and calcium from bonefrom bone

HematocritHematocrit

• Anemia is common in chronic failureAnemia is common in chronic failure

• Due to inadequate production of Due to inadequate production of erythropoietinerythropoietin

ProteinsProteins

• Proteinuria and a catabolic state Proteinuria and a catabolic state contribute to the negative nitrogen contribute to the negative nitrogen balancebalance

• Proteinuria can independently cause Proteinuria can independently cause renal damage by promoting renal damage by promoting inflammation and fibrosisinflammation and fibrosis

Systemic Effects of UremiaSystemic Effects of Uremia

• SkeletalSkeletal Bone inflammationBone inflammation

• CVSCVS Hypertension, pulmonary Hypertension, pulmonary edemaedema

• NeurologicNeurologic Encephalopathy, Encephalopathy, neuropathyneuropathy

• EndocrineEndocrineGrowth retardation, Growth retardation, osteomalaciaosteomalacia

Systemic Effects of UremiaSystemic Effects of Uremia

• HematologicHematologic AnemiaAnemia

• GIGI Anorexia, ulcers, GI Anorexia, ulcers, GI bleedingbleeding

• ImmunologicImmunologic Increased infectionsIncreased infections

• ReproductiveReproductive Sexual dysfunction, Sexual dysfunction, menstrual menstrual abnormalitiesabnormalities

Urinary Tract Infections (UTIs)Urinary Tract Infections (UTIs)

• Usually due to bacteriaUsually due to bacteria

• At risk groupsAt risk groups– Premature newbornsPremature newborns– Prepubertal childrenPrepubertal children– Sexually active womenSexually active women– Elderly men and womenElderly men and women– Diaphragm and spermatocide usersDiaphragm and spermatocide users


• Diagnosed by culture of specific oraganismsDiagnosed by culture of specific oraganisms• Usually due to retrograde movement of Usually due to retrograde movement of

causative organismcausative organism• Can occur anywhere along the urinary tractCan occur anywhere along the urinary tract• Usually involve gram-negative organisms Usually involve gram-negative organisms • Gram-positive organisms less common causeGram-positive organisms less common cause


Protection against UTIs include:Protection against UTIs include:• MicturitionMicturition• Low pH and presence of urea in urine are Low pH and presence of urea in urine are

bacteriocidalbacteriocidal• Uterovesical junction closes during bladder Uterovesical junction closes during bladder

contraction to prevent urine refluxcontraction to prevent urine reflux• Longer urethra and prostatic secretion Longer urethra and prostatic secretion

decrease the risk of infection in mendecrease the risk of infection in men

Consequences of UTIsConsequences of UTIs

• InfectionInfection

• Renal and ureter damageRenal and ureter damage

• Inability to conserve sodium and waterInability to conserve sodium and water

• Inability to excrete potassium and Inability to excrete potassium and hydrogen ionhydrogen ion

• Increased risk of dehydration and Increased risk of dehydration and metabolic acidosismetabolic acidosis

Types of UTIsTypes of UTIs

• CystitisCystitis

• Nonbacterial cystitisNonbacterial cystitis

• Acute or chronic pyelonephritisAcute or chronic pyelonephritis

CystitisCystitis

• Inflammation of bladderInflammation of bladder

• Most common site of UTIMost common site of UTI

• More common in womenMore common in women– Shorter urethraShorter urethra– Proximity of urethra to anusProximity of urethra to anus– Bacterial contamination from vaginal Bacterial contamination from vaginal

secretionssecretions

CystitisCystitis

• Most common infecting organismsMost common infecting organisms– E coliE coli

– KlebsiellaKlebsiella

– ProteusProteus

– PseudomonasPseudomonas

– StaphylococcusStaphylococcus

• Introduction of bacteria and an environment Introduction of bacteria and an environment that promotes bacterial growth are common that promotes bacterial growth are common factorsfactors

CystitisCystitis

• Many patients are asymptomaticMany patients are asymptomatic

• Symptoms includeSymptoms include– Increased urinary frequency and urgencyIncreased urinary frequency and urgency– DysuriaDysuria

• Hematuria, cloudy urine and flank pain Hematuria, cloudy urine and flank pain represent more serious symptomsrepresent more serious symptoms

Non-bacterial CystitisNon-bacterial Cystitis

• Women with symptoms of cystitis but Women with symptoms of cystitis but negative urine culturesnegative urine cultures

• More common in women 20-30 yrs of ageMore common in women 20-30 yrs of age

• Referred to as ‘urethral syndrome’Referred to as ‘urethral syndrome’

• Caused by inflammed or infected Caused by inflammed or infected microscopic paraurethral glands located microscopic paraurethral glands located in the distal third of the urethrain the distal third of the urethra

Interstitial CystitisInterstitial Cystitis

• Persistent and chronic form of Persistent and chronic form of nonbacterial cystitisnonbacterial cystitis

• Occurs primarily in womenOccurs primarily in women

• May be due to an autoimmune responseMay be due to an autoimmune response

Acute Pyelonephritis

• Infection of the renal pelvis and Infection of the renal pelvis and interstitiuminterstitium

• Causative organism is usually bacterial Causative organism is usually bacterial but may involve fungi or virusesbut may involve fungi or viruses

• Common risk factorsCommon risk factors– Urinary obstructionUrinary obstruction– Urine refluxUrine reflux

Common Causes of PyelonephritisCommon Causes of Pyelonephritis

• Kidney stonesKidney stones

• VesicoureteralVesicoureteral

• PregnancyPregnancy

• Neurogenic bladderNeurogenic bladder

• InstrumentationInstrumentation

• Female sexual traumaFemale sexual trauma


• Most common in womenMost common in women

• Responsible organismResponsible organism– E coliE coli– ProteusProteus– PseudomonasPseudomonas

• Infection occurs through ascension along Infection occurs through ascension along uretersureters


• Onset of symptoms is acute with feverOnset of symptoms is acute with fever

• May be difficult to differentiate from May be difficult to differentiate from cystitis by clinical symptomscystitis by clinical symptoms

• Specific diagnosis is established by urine Specific diagnosis is established by urine cultureculture

Chronic Pyelonephritis

• Persistent or recurrent autoimmune Persistent or recurrent autoimmune infectioninfection

• Inflammation and scarring evidentInflammation and scarring evident

• More likely to occur in patients with More likely to occur in patients with obstructive pathologic conditionsobstructive pathologic conditions


• Elimination of bacteria with normal Elimination of bacteria with normal urine flow is preventedurine flow is prevented

• Progressive inflammation results in Progressive inflammation results in fibrosis and scarringfibrosis and scarring

• Urine concentrating ability is impairedUrine concentrating ability is impaired

• Can lead to chronic renal failureCan lead to chronic renal failure


• Early symptoms are often minimal Early symptoms are often minimal

• May include hypertensionMay include hypertension

• May be similar to acute pyelonephritisMay be similar to acute pyelonephritis

SummarySummary

• Kidneys are involved in a number of processes Kidneys are involved in a number of processes which are important for maintenance of which are important for maintenance of homeostasishomeostasis

• Age-related changes in renal function can have Age-related changes in renal function can have profound effects and alters the patient’s profound effects and alters the patient’s response to drugsresponse to drugs

• Renal pathology produces predictable changes Renal pathology produces predictable changes in patients which are associated with in patients which are associated with alterations in homeostasisalterations in homeostasis

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Genitourinary Pathophysiology Randall L. Tackett, Ph.D