19 Kidney Disorders

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19 Kidney Disorders

Renal Function Overview

Excretes harmful waste products

Examples-urea, creatinine, uric acid

Renal Function Overview





Maintains

acid-base homeostasis

Controls the synthesis and excretion of bicarbonate and hydrogen ions

Reabsorbs essential substances

Examples-sodium, glucose, amino acids

Regulateswater and

sodiummetabolism

1. Controls water by concentrating and diluting urine

2. Controls sodium reabsorption in the proximal and distal collecting tubules

Maintainsasculartone

1. !ngiotensin "" #!$""%a. &asoconstricts peripheral resistance arterioles and efferent arteriolesb. 'timulates the synthesis and release of aldosterone

2. Renal-deried prostaglandin #()E2%

o &asodilates the afferent arterioles


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(roduces erythropoietin

'ynthesi*ed in the endothelial cells in the peritubular capillaries

Maintains calcium homeostasis&itamin + promotes bone minerali*ation by stimulating the release of alalinephosphatase from osteoblasts. !laline phosphatase hydroly*es pyrophosphate andother inhibitors of calcium-phosphate crystalli*ation.

1. 'econd hydroxylation of itamin +a. 1--ydroxylase is synthesi*ed in the proximal renal tubule cells.b. Conerts 2/-hydroxycholecalciferol to 1,2/-dihydroxycholecalciferol.

2. 0unctions of itamin +a. "ncreases gastrointestinal reabsorption of calcium and phosphorusb. (romotes bone minerali*ation

c. "ncreases the production of osteoclasts from macrophage stem cells

Important Laboratory Findings in Renal Disease

ematuriapage 3

page /

1. 4pper urinary tract #idneys, ureter% causes of hematuriaa. Renal stoneb. )lomerulonephritis

Characteri*ed by dysmorphic R5Cs #irregular membrane%

c. Renal cell carcinoma2. 6ower urinary tract #bladder, urethra, prostate% causes of hematuria

a. "nfectionb. $ransitional cell carcinoma

Most common cause of gross hematuria in the absence of infection

c. 5enign prostatic hyperplasia Most common cause of microscopic hematuria in adult males

. +rugs associated with hematuriaa. !nticoagulants #warfarin, heparin%b. Cyclophosphamide

ii emorrhagic cystitis

iii Ris factor for transitional cell carcinoma

ematuriapage 3

page /


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1. 4pper urinary tract #idneys, ureter% causes of hematuriaa. Renal stoneb. )lomerulonephritis

Characteri*ed by dysmorphic R5Cs #irregular membrane%

c. Renal cell carcinoma2. 6ower urinary tract #bladder, urethra, prostate% causes of hematuria

a. "nfectionb. $ransitional cell carcinoma

Most common cause of gross hematuria in the absence of infection

c. 5enign prostatic hyperplasia Most common cause of microscopic hematuria in adult males

. +rugs associated with hematuriaa. !nticoagulants #warfarin, heparin%b. Cyclophosphamide

ii emorrhagic cystitis

iii Ris factor for transitional cell carcinoma

(roteinuria

1. )enerala. (rotein aboe 1/7 mg823 hours or oer 7 mg8d6 #dipstic%b. (ersistent proteinuria usually indicates renal disease.c. 9ualitatie tests include dipstics and sulfosalicylic acid #''!%.

i. +ipstics are specific for albumin.ii. ''! detects albumin and globulins.

d. 9uantitatie test is a 23-hour urine collection.

2. $ypes of proteinuria

Table 19-1 Types o! "roteinuria

Type De!inition #auses

0unctional (rotein :2g823 hoursNotassociated with renal disease

0eer, exercise, congestie heart failure;rthostatic #postural%< occurs with standing and is absent inthe recumbent state= urine protein is absent in the firstmorning oid= noprogression to renal disease

;erflow (rotein loss is ariable6ow-molecular-weight proteinuria

!mount filtered >tubular reabsorption

Multiple myeloma with 5? proteinuriaemoglobinuria< e.g., intraascular hemolysisMyoglobinuria< crush in@uries, Mc!rdleAs glycogenosis#deficient muscle phosphorylase% increase in serum creatineinase

)lomerular Bephritic syndrome< protein >1/7 mg823hours but :./g823 hoursBephrotic syndrome< protein >./g823 hours

6oss of negatie charge on )5M< selectie proteinuria withloss of albumin and notglobulins= example is minimal changedisease+amage of )5M< nonselectie proteinuria with loss of albuminand globulins= example is membranous glomerulopathy

$ubular (rotein :2g823 hours+efect in proximal tubule reabsorption oflow-molecular-weight proteins #e.g., aminoacids% at normal filtered loads

eay metal poisoning< e.g., lead and mercury poisoning0anconi syndrome< inability to reabsorb glucose, amino acids,uric acid, phosphate, bicarbonate, and uric acidartnupAs disease< defect in reabsorption of neutral aminoacids #e.g., tryptophan% in the gastrointestinal tract andidneys


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5?, 5ence ?ones protein= )5M, glomerular basement membrane.

Renal Function Tests

'erum blood urea nitrogen #54B%

Bormal serum 54B to 1D mg8d6

1. End product of amino acid and pyrimidine metabolisma. (roduced by the lier urea cycleb. 0iltered in the idneys

(artly reabsorbed in the proximal tubule

c. 'erum leels depend on the following1/%.

i. (ersistent obstruction causes renal a*otemia #ratio 1/%.

Creatinine clearance #CCr%Elderly patients normally hae a decrease in CCr. $herefore, it is important tocalculate the dose and dose interal for drugs that are nephrotoxic #e.g.,aminoglycosides% in order to aoid precipitating acute renal failure due tonephrotoxic acute tubular necrosis.

1. Correlates with )0Ra. !nnual decrease in CCr of 1 m68min beyond age /7b. 4seful in detecting renal dysfunction

2. Creatinine clearance #CCr% formula

a. Measured CCr I 4Cr #mg8d6% J & #m68min% K (Cr #mg8d6%i. & I olume of a 23-hour urine collection in m68min and 4Cr and (Cr the

creatinine concentration of urine and plasma, respectiely.ii. CCr results are dependent on a correct 23-hour urine collection.

b. Bormal adult CCr is to 1 m68min.i. "n general, a CCr below 177 m68min is abnormal.ii. CCr below 17 m68min indicates renal failure.

. Causes of increased and decreased CCr

Table 19-) #auses o! Increased and Decreased #reatinine #learance *##r+

#auses Discussion

Increased ##r

Bormal pregnancy Bormal increase in plasma olume causes an increase in the )0R leading to an increase inCCr= highest at the end of the first trimester

Early diabeticglomerulopathy

Efferent arteriole becomes constricted due to hyaline arteriolosclerosis causing an increasein the )0R and CCr"ncreased )0R damages the glomerulus #hyperfiltration in@ury%

Decreased ##r

Elderly people )0R normally decreases with age causing a corresponding decrease in the CCr

!cute and chronic renaldisease

!R0 due to acute tubular necrosis, CR0 due to diabetic glomerulopathy

!R0, acute renal failure= CR0, chronic renal failure= )0R, glomerular filtration rate.

4rinalysis

Table 19-, 'rinalysis

Feature Tested Result #ause


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eneral ./amination

Color +ar yellowRed or pin

Concentrated urine #e.g., olume depletion%,bilirubinuria, increased 45)ematuria, hemoglobinuria, myoglobinuria

'pecific graity 0ixed #e.g., 1.717%"nability to concentrate urine

6ac of concentration and dilution #e.g., chronic renalfailure%0irst sign of intrinsic renal disease

#0emical Dipstics p !cid or alaline p +etermined by diet and acid-base status

!laline urine in Proteusinfections< urease conertsurea to ammonia

(rotein (roteinuria +etects albumin #notglobulins%''!< detects albumin and globulins #e.g., 5? protein%

!lbuminuria< dipstic and ''! hae the same results5? protein< ''! greater than dipstic result

)lucose "ncreased serum glucose glucosuriaBormal serum glucose glucosuria

+iabetes mellitusBormal pregnancy, benign glucosuria< both conditionshae decreased renal threshold for glucose

Fetones Fetonuria +iabetic etoacidosis, staration, etogenic diets$est only detects acetone and !c!c #notL-;5%

5ilirubin 5ilirubinuria &iral hepatitis, obstructie @aundice

4robilinogen #trace

amount normal%

!bsent

"ncreased

;bstructie @aundice

&iral hepatitis, extraascular hemolytic anemia #e.g.,spherocytosis%

5lood emoglobinuriaematuriaMyoglobinuria

"ntraascular hemolytic anemiaRenal calculus, infection, cancer #renal cell carcinoma,transitional cell carcinoma%Crush in@uries

Bitrites "ncreased (roduced by nitrate-reducing uropathogens #e.g.,Escherichia coli%

6euocyte esterase (resence of esterase in neutrophils#pyuria%'terile pyuria #neutrophils present butnegativestandard urine culture%

"nfections #e.g., urethritis, cystitis, pyelonephritis%Chlamydia trachomatisurethritis, renal tuberculosis

%ediment

Cells 5acteriaRed blood cells #hematuria%

Beutrophils #pyuria%;al fat bodies

4sually sign of 4$"Renal stone, cancer #bladder, renal%,

glomerulonephritis #R5Cs are dysmorphic%, infection,5("nfection, sterile pyuriaRenal tubular cells with lipid #nephrotic syndrome%

Casts yalineRed blood cellHhite blood cellRenal tubular cell0attyHaxy #refractile, acellular%5road

Nosignificance in absence of proteinuriaBephritic type of glomerulonephritis #e.g.,poststreptococcal glomerulonephritis%

!cute pyelonephritis, acute tubulointerstitial nephritis#drugs%

!cute tubular necrosisBephrotic syndrome #e.g., minimal change disease%'ign of chronic renal failure;ften hae a large diameter due to tubular atrophy#broad casts%'ign of chronic renal failureHaxy cast with an increased diameter

Crystals Calcium oxalate4ric acidCystine

(ure egan diet, ethylene glycol poisoning, calciumoxalate calculiyperuricemia associated with gout or massiedestruction of cells after chemotherapyCystinuria, hexagonal cystine crystals

!c!c, acetoacetic acid= 5?, 5ence ?ones= 5(, benign prostatic hyperplasia= L-;5, hydroxybutyric acids= ''!, sulfosalicylic acid=45), urobilinogen= 4$", urinary tract infection.

)old standard test in the initial worup of renal disease


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#linical 2natomy o! t0e Kidney

5lood supply of the idneypage 377

page 371

1. Renal cortex receies 7 of the blood supply.2. Renal medulla is relatiely ischemic due to reduced blood supply.. Renal essels are end arteries.

a. Nocollateral circulationb. ;cclusion of any branch of a renal artery produces infarction.

3. !fferent arteriolesa. Contain the @uxtaglomerular apparatus

(roduces the en*yme renin

b. 5lood flow is controlled by renal-deried ()E2#asodilator%.c. +irect blood into the glomerular capillaries

/. Efferent arterioles

a. +rain the glomerular capillariesb. 5lood flow controlled by !$"" #asoconstrictor%

c. Eentually become the peritubular capillaries

Bonsteroidal anti-inflammatory drugs #B'!"+s% inhibit production of ()E2= therefore,intrarenal blood flow is controlled by the efferent arterioles, whose blood flow ismaintained by !$"", a asoconstrictor. $his increases the ris of ischemic damage tothe medulla.

5lood supply of the idneypage 377

page 371

1. Renal cortex receies 7 of the blood supply.2. Renal medulla is relatiely ischemic due to reduced blood supply.. Renal essels are end arteries.

a. Nocollateral circulationb. ;cclusion of any branch of a renal artery produces infarction.

3. !fferent arteriolesa. Contain the @uxtaglomerular apparatus

(roduces the en*yme renin

b. 5lood flow is controlled by renal-deried ()E2#asodilator%.c. +irect blood into the glomerular capillaries

/. Efferent arterioles

a. +rain the glomerular capillariesb. 5lood flow controlled by !$"" #asoconstrictor%

c. Eentually become the peritubular capillaries

Bonsteroidal anti-inflammatory drugs #B'!"+s% inhibit production of ()E2= therefore,intrarenal blood flow is controlled by the efferent arterioles, whose blood flow ismaintained by !$"", a asoconstrictor. $his increases the ris of ischemic damage tothe medulla.


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'tructure of the glomerulus1. )lomerular capillaries contain fenestrated epithelium.

o oles in the endothelial surface are important in the filtration process.

2. )lomerular basement membrane #)5M%

a. Composed of type "& collagen

b. 'i*e and charge are the primary determinants of protein filtration.

i. eparan sulfate produces the negatie charge of the )5M.ii. Cationic proteins of low molecular weight #6MH% are permeable.iii. !lbumin has a strong negatie charge and is notpermeable.

6oss of the negatie charge causes loss of albumin in the urine.

i. )5M is permeable to water and 6MH proteins #e.g., amino acids%.c. Causes of )5M thicening

i. +eposition of immunocomplexes Example-membranous glomerulopathy

ii. "ncreased synthesis of type "& collagen Example-diabetes mellitus

2. &isceral epithelial cells #&EC%a. (rimarily responsible for production of the )5M

b. Contain podocytes #foot-lie processes% and slit pores between the podocytes

'ere as a distal barrier for preenting protein loss in the urineii 0usion of the podocytes is present in any cause of the nephrotic syndrome.

2. Mesangial cellsii 'upport the glomerular capillaries

ii Can release inflammatory mediators and proliferate

Example-"g! glomerulonephritis. (arietal epithelial cells

ii 6ining cells of 5owmanAs capsule

ii (roliferation causes NcrescentsN that destroy the glomerulus.

#ongenital Disorders and #ystic Diseases o! t0e Kidneys

orseshoe idney

1. Most common congenital idney disorder2. Ma@ority #7% are fused at the lower pole

o Fidney is trapped behind the root of the inferior mesenteric artery.

. Clinical findings

a. "ncreased incidence with $urnerAs syndrome

b. +anger of infection and stone formation

orseshoe idney


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1. Most common congenital idney disorder2. Ma@ority #7% are fused at the lower pole

o Fidney is trapped behind the root of the inferior mesenteric artery.

. Clinical findings

a. "ncreased incidence with $urnerAs syndrome

b. +anger of infection and stone formation

Cystic diseases of the idney

Table 19-3 #ystic Diseases o! t0e Kidneys

#ystic Disease Discussion

Renal dysplasia Most common cystic disease in children

Noinheritance pattern!bnormal deelopment of one or both idneys= abnormal structures persist in the idneys#e.g., cartilage, immature collecting ductules%(resent as an enlarged, irregular, cystic, unilateral #bilateral% flan mass5ilateral dysplastic idneys may lead to renal failure= account for 27 of cases of CR0 inchildren

?uenile polycysticidney disease

!utosomal recessie inheritance5ilateral cystic disease= cysts in the cortex and medullaCysts also occur in the lier= association with congenital hepatic fibrosis leading to portalhypertensionEnlarged idneys at birth= most serious types are incompatible with lifeMaternal oligohydramnios #decreased amniotic fluid%= newborns hae (otterAs facies, adeformation due to oligohydramnios= findings include low-set ears, parrot bea nose, and lunghypoplasia

!dult polycystic idneydisease #0ig. 1-2%

!utosomal dominant inheritance5ilateral cystic disease deelops by 27-2/ years of age= bilaterally palpable idneys= cysts

inole all parts of nephron in cortex and medullaCysts are present in the lier #37 of cases% and pancreasypertension #>D7 of cases%= associated with stroe due to rupture of intracranial berryaneurysms #aneurysms in 17-7 of cases% or intracerebral hemorrhageCR0 begins at age 37-G7 years= due to destruction of idneys by slowly expanding cysts=accounts for 17 of cases of CR0= most common cause of death from cystic disease;ther findings< sigmoid dierticulosis, hematuria, mitral ale prolapse, ris for deelopingrenal cell carcinoma

Medullary spongeidney

Noinheritance patternMost commonly discoered with an "&(= striations are present in the papillary ducts of themedulla #N'wiss-cheeseN appearance%= multiple cysts of the collecting ducts are present in themedullaRecurrent 4$"s, hematuria, and renal stones

!cOuired polycysticidney disease

Most common cause is renal dialysis= occurs in /7 of patients on long-term dialysis$ubules are obstructed by interstitial fibrosis or oxalate crystals'mall ris for deeloping renal cell carcinoma

'imple retention cysts Most common adult renal cyst+eried from tubular obstructionMay produce hematuriaReOuires needle aspiration to distinguish it from renal cell carcinoma

CR0, chronic renal failure= "&(, intraenous pyelogram= 4$"s, urinary tract infections.
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lomerular Disorders

$erminology of glomerular disease

Table 19-4 (omenclature and Description o! lomerular DisordersTerm Description

0ocal glomerulonephritis ;nly a few glomeruli are abnormal

+iffuse glomerulonephritis !ll glomeruli are abnormal

(roliferatie glomerulonephritis >177 nuclei in affected glomeruli

Membranous glomerulopathy $hic )5M, no proliferatie change

Membranoproliferatieglomerulonephritis

$hic )5M, hypercellular glomeruli

0ocal segmental glomerulosclerosis 0ibrosis inoling only a segment of the inoled glomerulus

Crescentic glomerulonephritis (roliferation of parietal epithelial cells around glomerulus

(rimary glomerular disease "noles only glomeruli and noother target organs #e.g., minimal changedisease%

'econdary glomerular disease "noles glomeruli and other target organs #e.g., '6E%

)5M, glomerular basement membrane= '6E, systemic lupus erythematosus.

Bormal glomerulus

$erminologyofglomerulardisease

Table 19-4 (omenclature and Description o! lomerular Disorders

Term Description

0ocal glomerulonephritis ;nly a few glomeruli are abnormal

+iffuse glomerulonephritis !ll glomeruli are abnormal

(roliferatie glomerulonephritis >177 nuclei in affected glomeruli

Membranous glomerulopathy $hic )5M, no proliferatie change

Membranoproliferatieglomerulonephritis

$hic )5M, hypercellular glomeruli

0ocal segmental glomerulosclerosis 0ibrosis inoling only a segment of the inoled glomerulus

Crescentic glomerulonephritis (roliferation of parietal epithelial cells around glomerulus

(rimary glomerular disease "noles only glomeruli and noother target organs #e.g., minimal changedisease%

'econdary glomerular disease "noles glomeruli and other target organs #e.g., '6E%

)5M, glomerular basement membrane= '6E, systemic lupus erythematosus.

Bormal glomerulus

Routine studies on biopsy specimens1. Pamp QE #hematoxylin and eosin% and other special stains

o 4sed to help classify the type of glomerular disease


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2. "mmunofluorescence #"0% stain

a. "dentifies patterns and type of protein deposition

b. 6inear pattern

i. "t is a characteristic finding in anti-)5M disease. Example-)oodpasture syndrome

ii. !ntibodies line up against eenly distributed antigens in the )5Mc. )ranular #Nlumpy-bumpyN% pattern

4sually indicates immunocomplex #"C% deposition in the glomerulus2. Electron microscopy

ii +etects submicroscopic defects in the glomerulus= examples

19 Kidney Disorders

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