RENAL CALCULI

STONE CHARACTERISTICS
URIC ACID Yellow to brownish red, moderately hard
Phosphate stones Pale and friable
Calcium oxalate Very hard, dark in color, rough surface
Cystine stones Yellow brown, somewhat greasy (old-soap)
• Patient experiences severe back pain in the lower back
• Lithotripsy- a procedure using high-energy shockwaves breaks down the stones
• pH, concentration, and urinary stasis favor calculi formation
• Magnesium ammonium phosphate is frequently accompanied by infections with urea-splitting
organisms and pH is often 7
• Uric acid calculi forms when pH is acidic
• Presence of microscopic hematuria resulting from irritation of to the tissues by moving
the calculus is the primary urinalysis finding
• Patient management- Controlling urine pH, Decreasing concentration by maintaining hydration,
dietary restrictions

AUTOMATION
I. Sysmex UF-100 Urine Cell Analyzer
• 2mL of urine is required
• Reagent strip is read through reflectance photometry
• Refractive index is measured through refractive index
• Clarity is measured through light transmittance and light scattered
• Utilizes flow cytometry with impedance detection, forward light scatter, and fluorescence
• DNA is stained with an orange dye phenathridine
• Carbocyanine stains the mitochondria, cell membrane and nuclear membrane a green color
II. Urisys 2400 system- minimum sample volume is 1.5 mL
III. Aution Max AX-4280- 1.0 mL of urine sample is used
IV. The iQ 200 Automated Urine Microscopy Analyzer- uses Auto Particle Recognition software
that classifies urine particles in the photograph based on size, shape, texture, and contrast

RENAL DISEASES
DISORDER ETIOLOGY CLINICAL COURSE
Acute Deposition of immune complexes, formed in Rapid onset of hematuria and
glomerulonephritis conjunction with group A glomerular edema
streptococcus infection Permanent renal damage seldom
occurs
Rapidly progressive Deposition of immune complexes from Rapid onset with glomerular
glomerulonephritis systemic immune disorders on the glomerular damage and possible progression
membrane to end-stage renal failure
Goodpasture Attachment of a cytotoxic antibody formed Hemoptysis and dyspnea followed
syndrome during viral respiratory infections to glomerular by hematuria
and alveolar basement membrane Possible progression to end-stage
renal disease
Wegener’s Antineutrophilic cytoplasmic auto-antibody Pulmonary symptoms including
granulomatosis binds to neutrophils in vascular walls producing hemoptysis develop first followed
damage to small vessels in the lungs and by renal involvement and possible
glomerulus progression to end-stage renal
failure
Henoch-Schonlein Occurs primarily in children following viral Initial appearance of purpura
purpura respiratory infections; a decrease in platelets followed by blood in sputum and
disrupts vascular integrity stools and eventual renal
involvement
Membranous Thickening of the glomerular membrane Slow progression to nephrotic
glomerulonephritis following deposition of IgG immune complex syndrome or possible remission
 Chronic Marked decreased in renal function resulting
glomerulonephritis from glomerular damage precipitated by other
renal disorders
IgA nephropathy Deposition of IgA on the glomerular membrane
resulting from increased levels of serum IgA
Nephrotic syndrome Disruption of the electrical charges that
produce tightly fitting podocyte barrier resulting
in massive loss of protein and lipids
Minimal change Disruption of the podocytes occurring primarily
disease in children following allergic reactions and
immunizations
Focal segmental Disruption of podocytes in certain areas of
glomerulosclerosis glomeruli associated with use of heroin and
analgesic abuse and AIDS
Alport syndrome Genetic disorder showing lamellated and
thinning of glomerular basement membrane
Noticeable decrease in renal
function progressing to renal
failure
Macroscopic hematuria
Slow progression to chronic
glomerulonephritis
Acute onset following systemic
shock
Gradual disorder from other
glomerular disorders and then to
renal failure
Frequent complete remission
following corticosteroid treatment
May resemble nephrotic syndrome
or minimal change disease
Slow progression to nephrotic
syndrome and end-stage renal
disease

DISORDER ETIOLOGY CLINICAL COURSE

Acute tubular Damage to the renal tubular cells caused by Acute onset of renal dysnfunction
necrosis ischemia or toxic agents usually resolved when the underlying
cause is corrected
Fanconi syndrome Inherited in association with cystinosis and Hartnup Generalized renal tubular
disease or acquired through exposure to toxic reabsorption defect
agents
Nephrogenic diabetes Inherited defect of tubular response to ADH or Requires supportive therapy to
insipidus acquired from medications prevent dehydration
Renal glucosuria Inherited autosomal recessive trait Benign disorder
Cystitis Ascending bacterial infection of the bladder Acute onset of urinary frequency
Acute pyelonephritis Infection of the renal tubules and interstitium related Acute onset of urinary frequency
to interference of urine flow to the bladder, reflux of
urine from the bladder, and untreated cystitis
Chronic Recurrent infection of the renal tubule and Possible progression to renal failure
pyelonephritis interstitium caused by structural abnormalities
affecting flow of urine
Acute interstitial Allergic inflammation of the renal interstitium in Acute onset of renal dysfucntion
nephritis response to certain medications

AMINO ACID DISORDERS

 Normally amino acids pass through the glomerulus and are reabsorbed by the proximal
tubules
 The reabsorption is an active transport process, is threshold limited and is facilitated by
membrane bound carriers

TYPES OF AMINO ACIDURIAS

1. OVERFLOW- caused by increased plasma levels of amino acid(s) such that the renal threshold
for amino acid reabsorption is exceeded, and additional amino acids are excreted in the urine

2. NO-THRESHOLD- also has an overflow mechanism, the difference is that there is no reabsorption
of amino acids, any increase in the blood produces an increased quantity in the urine

3. RENAL- plasma levels of amino acids are normal, but because of a tubular defect, they are
not reabsorbed and appear in the urine in increased amounts
 Aminoacidurias may occur as:
1. Primary (inborn error of metabolisms) - result from an inherited defect which may be due to:
i. enzyme that is defective or deficient in the amino acid metabolic pathway
ii. Tubular reabsorptive dysfunction may occur

2. Secondary- induced, most notably by severe liver disease or through generalized renal tubular
dysfunction (E.g. Fanconi syndrome)

A. CYSTINOSIS
 An inherited lysosomal storage disease that results in the intracellular deposition of cystine
in the lysosomes of cells throughout the body, particularly the kidneys, eyes, bone marrow, and
spleen. The accumulated cystine crystallizes within cells, causing damage and disrupting cellular
function.

TYPES
1. Nephropathic- most common and severe form
 Accumulated cystine crystallizes in the within the proximal tubule cells of the nephrons,
causing generalized proximal tubular dysfunction and the development of Fanconi syndrome.

2. Intermediate cystinosis- Same clinical features as nephropathic cystinosis, however the onset of
symptoms occurs in adolescence, and the disorder has a slower rate of progression.

3. Ocular cystinosis- manifest only ocular impairment caused by cystine deposition in the cornea

B. CYSTINURIA
 A disorder characterized by the urinary excretion of large amounts of cystine and the dibasic
amino acids- arginine, lysine, ornithine
 The presence of increased urinary cystine is not due to a defect in the metabolism of cystine
but, rather, to the inability of the renal tubules to reabsorb cystine filtered by the
glomerulus

C. HOMOCYSTINURIA
 Defects in the metabolism of the amino acid methionine produce an increase in homocystine
throughout the body
 Increased homocystine may result to failure to thrive, cataracts, mental retardation,
thromboembolic problems, and death

D. BRANCHED-CHAIN AMINO ACID DISORDERS

1. MAPLE SYRUP URINE DISEASE
 Characterized by the accumulation of branched chain amino acids- leucine, isoleucine,
and valine
 Deficiency in branched chain a-keto acid dehydrogenase (BCKD)
 Urine smells like maple syrup due to the accumulation of keto acids in the urine
 MSUD is included in many newborn screening profiles using MS/MS
 Urine screening test most frequently performed for keto acids is the 2,4-
dinitrophenyhydrazine (DNPH) reaction

2. ORGANIC ACIDEMIAS
 Isovaleric acidemia- may be suspected when urine specimen or the patient smells like sweaty
feet
- Caused by the accumulation of isovalerylglycine due to a deficiency in isovaline coenzyme A
in the leucine pathway

E. PHENYLKETONURIA
 A disease characterized by increased urinary excretion of phenylpyruvic acid and its
metabolites
 Due to phenylalanine hydroxylase deficiency
 Within the infant’s first 2-3 weeks of life, high plasma levels of phenylalanine cause brain injury,
with maximum detrimental effects achieved by 9 months of age
 The urine, sweat, and breath of patients with PKU have a characteristic mousy odor, which is
caused by the phenylacetic acid in these fluids
 Phenylalanine competitively inhibits the enzyme tyrosinase, which decreases the production of
melanin form tyrosine

F. ALKAPTONURIA
 Characterized by excretion of large amounts of homogentisic acid
 The disease was called alkaptonuria because of the unusual darkening of the urine when
alkali is added
 Deficiency in homogentisic acid oxidase

G. TYROSINURIA
 Tyrosine is a metabolic precursor of several compounds- melanin, thyroxine, and cathecolamines
TYPES
1. Transient neonatal tyrosinemia- due to the immature liver of infants and inadequate liver
enzymes to metabolize tyrosine.

2. Inherited tyrosinemias
Type I- AKA tyrosinosis, is caused by a defect in the enzyme fumaryl acetoacetate
hydrolase
Type II- A defect in tyrosine aminotransferase

H. MELANURIA
 When inherited defects occur in melanin production, hypomelanosis or albinism results
 Increased production of melanin and its colorless precursors will cause an increase in urinary
excretion of melanin and its colorless precursors will cause an increase in the urinary excretion of
melanin or melanuria
E.g. melanoma
 When melanin and its precursors are present in urine, the urine color darkens with
exposure to sunlight

I. TRYPTOPHAN DISORDERS
1. INDICANURIA
 In intestinal disorders, increased amounts of tryptophan are converted to indole, the
excess indole will be circulated to the liver and is converted to indican and excreted in the urine
E.g. obstruction, presence of abnormal bacteria, malabsorption syndrome, and Hartnup disease
 Indican in the urine is colorless until oxidized to dye indigo blue by exposure to air
 Early diagnosis of Hartnup disease is sometimes made when mother’s report a blue staining of
their infant’s diaper, referred to as “blue diaper syndrome”.

2. 5-HYDROXYINDOLEACETIC ACID
 Serotonin is produced in the tryptophan pathway for the stimulation of smooth muscles
 Serotonin is produced by the argentaffin cells in the intestine and is carried through the body
primarily by platelets
 Normally, the body uses most of the serotonin, and only small amounts of its degradation product
5-hydroxyindoleacetic acid (HIAA) are available for excretion in the urine
 However, when carcinoid tumors involving the argentaffin (enterochromaffin) cells
develop, excess amounts of serotonin are produced, resulting in the elevation of urinary 5-
HIAA levels