KIDNEY

LOWER URINARY TRACT

Pages 500-527 RR Path 4th edition

Afferent arteriole

Glomerulus

Efferent arteriole

15

Amount
reabsorbed
is dependent
on GFR

BUN

Filtered, partly reabsorbed.

High levels lost in skin
(renal failure).

Creatinine

Only filtered in kidney. Not

reabsorbed or secreted.

Normal

Filtrate

BUN:Cr
ratio
remains
15

Afferent arteriole

GFR
Backed up
but ratio
remains
same

Glomerulus

Efferent arteriole

15

Reabsorption
due to GFR

BUN

BUN:Cr
ratio >15
e.g., 80/4

Creatinine

Prerenal azotemia
Cardiac output
(e.g., CHF)

Filtrate

Glomerulus
Skin, GI
GFR
Backed up
but ratio is
decreased
due to loss
via skin,
GI tract

< 15

BUN
Creatinine

Renal azotemia
Renal failure

Filtrate

No
reabsorption
because the
proximal
tubules are
either damaged
or sloughed off

BUN:Cr
ratio <15
e.g., 80/8

URINALYSIS
Dipstick only detects albumin. SSA detects albumin + globulins
(e.g. BJ protein). If similar results in the 2 tests, then protein
is albumin. If SSA is higher than the dipstick, then globulins
(e.g., light chains) are also present. Insurance companies will
assume the person has kidney disease if proteinuria is present.
Diabetes mellitus until proven otherwise. First step is to order
a blood glucose.
Dipstick only detects acetone and AcAc.
It does not detect -OHB (alcoholic).
Normal finding in starvation, ketogenic diet, pregnancy

URINALYSIS
Never normal in urine. CB present. Hepatitis, cholestasis
Normal color of urine. Colon bacteria convert
conjugated bilirubin into urobilinogen (color of stool and
urine).
U BILIRUBIN
EHA
Hepatitis
Obstructive

U Urobilinogen

++

++
++

++

Discussed
in liver
lectures

URINALYSIS
Detects Hb/RBCs, myoglobin
Nitrite

Most uropathogens nitrate reducers UTI

Chlamydia

Esterase

++

++

++

Called sterile pyuria:

Enzyme from neutrophils
standard cultures do not
detect Chlamydia. Chlamydia
is not a nitrate reducer, so
nitrites are negative.
Esterase is + because
neutrophils are present.

RENAL DYSPLASIA

MC cystic disease. Unilateral palpable flank mass in

newborn.

JUVENILE POLYCYSTIC

AR. Bilateral (incompatible with life). Oligohydramnios.

Potters facies (deformation).

ADULT POLYCYSTIC

AD. Bilateral. Cysts develop by 20-25 yrs old. Hypertension,

berry aneurysms (subarachnoid bleed). CRF 40-60 yrs old.

Endothelial cell
Negative charge due to
heparan sulfate. Repels
negative charge of albumin.

Red dots are IgG

antibodies against
antigen (white dots) in
GBM. Fenestra are gaps
in endothelial cell.
Responsible for crescents

GBM

Linear IF
Goodpastures

Note podocytes

ICs have different sizes and charge. Large

ICs cannot get thru GBM (become subendothelial deposits). Those ICs that are small
get thru GBM but get trapped in mesangium
or beneath VEC (subepithelial deposits).

Granular ICs
Can determine composition
of ICs (e.g., IgG, IgA,
DNA)

NORMAL GLOMERULUS

RBC in lumen

GBM

Fusion of podocytes. All cases of nephrotic syndrome

have fusion of the podocytes.
No spaces between the toes

RBC in lumen

GBM

Post-streptococcal GN Membranous GN
Subepithelial EDD (ICs are small enough to pass thru the GBM).
Notice that the GBM is above the EDD; therefore, the EDDs must
have passed thru it to be on the epithelial side of the GBM.

GBM

CAPILLARY
LUMEN
NUCLEUS
SLE type IV, MPGN type I

Subendothelial EDD. ICs did not get thru the GBM but
are right underneath the endothelial cell nucleus.

NEPHRITIC SYNDROME

Key findings in nephritic GN: RBC casts, hematuria, mild to moderate

proteinuria. Urinalysis findings in slide: RBC cast (large red arrow);
dysmorphic RBCs (damaged; similar to schistocytes in MIHA; small red
arrows and black arrows in phase contrast; appearance of a normal
RBC (red circle; understand that it is not normal to have RBCs in the
urine, but this what they would look like).

Overall MC glomerulopathy. Pathogenesis: IgA-anti-IgA ICs (type

III HSR). EDDs deposit in mesangial matrix. Probably part of
Henoch-Schnlein purpura complex. Usually follows viral URI.
Hypertension. Slow progression to CRF
Group A Streptococcus infection of pharynx (pharyngitis/skin
(scarlet fever). MC infectious GN. ICs produce subepithelial EDDs.
Hypertension transient. Periorbital edema from retention of sodium.
Anti-DNAase B present in serum. ASO degraded in skin infections.

Diffuse (all glomeruli involved), proliferative (numerous nuclei),

glomerulonephritis (contains neutrophils; acute inflammation).
Excellent prognosis. Rarely progress to CRF.

MC subtype in SLE. ICs DNA-anti-dsDNA (type III HSR).

Subendothelial EDDs. Histology similar to post-streptococcal GN
except for wire-looping/hematoxylin bodies. Hypertension. Anti-dsDNA antibodies in serum. Poor prognosis.
Goodpastures, Wegeners, microscopic polyangiitis. No EDDs. Linear
IF with Goodpasture syndrome (anti-GBM antibodies; begins with
hemoptysis and ends with renal failure; type II HSR). Very poor
prognosis.

Crescentic GN (proliferating
parietal epithelial cells; arrows)

NEPHROTIC SYNDROME
Definition: protein >3.5
gm/24 hrs
No inflammation in glomeruli
Hypoalbuminemia
Hypercholesterolemia (type
II hyperlipoproteinemia)
Thrombogenic (e.g., renal
vein thrombosis due to
ATIII [lost in urine])
Hypogammaglobulinemia
(some cases)
Ascites,
pitting edema (oncotic
Fatty cast polarized (Maltese cross
due to cholesterol) and/or oval fat
pressure from
bodies (renal tubular cells with
hypoalbuminemia)
cholesterol)

MC cause of nephrotic syndrome in children. Only albuminuria.

T cell cytokines cause a temporary loss of the negative charge
of the GBM. Normal glomeruli/tubules. EM only shows fusion of
podocytes. No EDDs. Negative IF. Excellent prognosis.

MC adult cause of nephrotic syndrome. MC type in young black

males with AIDS. MC renal disease in IV heroin abuse. Nonselective proteinuria. Microscopic hematuria. Hypertension. No
EDDs or IF. Very poor prognosis.

HBV association, drugs, 20 syphilis. Subepithelial EDDs.

Epimembranous spikes (subepithelial- arrows). H&E, silver
stain below.

Thick membranes. No increase in nuclei.

High association with HCV (less common in HBV), drugs,

cryoglobulins. Subendothelial EDDs. Tram tracks (mesangium
splits GBM). Hypertension. Hematuria. Poor prognosis.

DIABETIC GLOMERULOPATHY
Efferent arteriole hyalinized first (blue arrow; hyaline arteriolosclerosis): leads to GFR and hyperfiltration injury of the glomerulus
manifested by microalbuminuria. Nonenzymatic glycosylation (NEG) of
the GBM makes it permeable to protein and pressure on glomerular
capillaries from hyalinization of efferent arterioles causes loss of
minute amounts of albumin in the urine, which is called microalbuminuria
(first lab sign of diabetic glomerulopathy).
ACE inhibitors open up efferent arteriole by
ATII (vasoconstrictor). This prevents hyperfiltration and loss of
protein.
Type IV collagen
+
trapped proteins

Afferent
arteriole
(PGE2; VD)

Nodular glomerulosclerosis

NEG of
efferent
arteriole
(ATII; VC)

DIABETIC GLOMERULOPATHY
Nodular glomerulosclerosis:
protein + type IV collagen

Efferent arteriole
(no ATII effect).
Afferent/efferent
arterioles will
eventually be
hyalinized if strict
glucose control is
not initiated.

ACUTE TUBULAR NECROSIS

Ischemic ATN
Prerenal azotemia MCC
(renal artery blood flow)
Coagulation necrosis
of proximal tubule and thick
ascending limb (TAL). BM
also damaged (regeneration
not possible)
Nephrotoxic ATN
Aminoglycosides MCC (must
dose adjust elderly), Pb,
IVP dye. Only affects
proximal tubule. BM intact
(regeneration possible).
BUN/Cr <15, hyperkalemia,
AG metabolic acidosis

Coagulation
necrosis of
tubules

RENAL TUBULAR CELL CAST

TIN: ACUTE PYELONEPHRITIS

UUT signs: fever, WBC casts (inset, arrows show neutrophils),
flank pain + LUT signs (frequency, dysuria, suprapubic pain)

Normal

VUR

Ascending infection (E. coli MC): urethra-bladderkidneys (if vesicoureteral reflux [VUR] is present;
note that angle of ureter entry into wall of bladder
does not prevent reflux)

CHRONIC PYELONEPHRITIS
U-shaped scars overlying blunt calyces (seen in IVP).
Tubules atrophic (look like thyroid gland) and glomeruli
become fibrosed.
Blunt
calyces

ACUTE DRUG-INDUCED TIN

Antibiotics, NSAIDS. Oliguria, fever, rash, eosinophilia/uria,

WBC casts. Type I and IV HSR. Withdraw drug and never
use again.

ANALGESIC NEPHROPATHY

Deadly duo: acetaminophen (FRs) destroy renal papillae, aspirin

PGE2 [a vasodilator] in afferent arteriole. ATII (a vasoconstrictor)
is controlling renal blood flow. Renal papillary necrosis occurs (ring
sign on IVP indicates absent papilla). Renal papillary necrosis also
occurs in acute pyelonephritis, sickle cell trait/disease.

URATE NEPHROPATHY
Aggressive Rx disseminated cancer causes release purines
producing urate crystals (picture on left) that blocks
tubules producing ARF. Use allopurinol first to block
XO
xanthine oxidase (xanthine
uric acid)!!!

MYELOMA KIDNEY
Light chains block tubule lumens and produce a foreign body
giant cell reaction (not multinucleated cells in tubules) leading
to renal failure (picture on right).

CHRONIC RENAL FAILURE

GFR < 10 mL/minute. DM MCC, hypertension, chronic
GN, cystic diseases.
EPO (anemia). Platelet aggregation (prolonged BT reversed with
dialysis.)
Hypovitaminosis D (no 1--Ohase
in proximal tubules) serum Ca2+
20 HPTH (osteomalacia, osteoporosis, osteitis fibrosa cystica
particularly in jaw)
Hypertension, pericarditis, CHF
Hemorrhagic gastritis
AG metabolic acidosis
Fixed specific gravity (1.010): no
concentration or dilution. Waxy
casts.

Waxy cast (sign of CRF)

NEPHROSCLEROSIS
Kidney of hypertension (HTN).
Hyaline arteriolosclerosis of
afferent/efferent arterioles
(microscopic) is the key finding
and leads to tubular atrophy
and glomerular fibrosis.

VASCULAR DISEASE

Malignant hypertension

Rapid BP (220/180) with encephalopathy and oliguric ARF.

Hyperplastic arteriolosclerosis (microscopic). Preexisting HTN,
systemic sclerosis. Medical emergency (lower BP immediately).

Renal infarction

Flank pain, hematuria (PAN, arterial emboli)

Sickle cell nephropathy

Hematuria (disease/trait). Loss concentration/dilution. Renal

papillary necrosis.

HYDRONEPHROSIS
Compression atrophy
cortex and medulla
MCC is a stone in
the ureter
BPH MCC if the
hydronephrosis is
bilateral

UROLITHIASIS
Hypercalciuria is the key metabolic abnormality in calcium
stones (reabsorb too much calcium from GI tract [absorptive
hypercalciuria])
Calcium oxalate is the MC stone
Calcium phosphate (dairy products)
Rx of calcium stones: hydrochlorothiazide if hypercalciuria is
present. Drink a lot of water (keep urine hypotonic).

PTH-mediated symporter;
reabsorption of calcium in
Na+ channel reduces calcium
in urine.

UROLITHIASIS
Staghorn calculus: Proteus infection produces urease
which produces ammonia and an alkaline pH urine. Stone
is composed of magnesium-ammonia-phosphate.

Uric acid stones

RENAL TUMORS
Causes: smoking, APKD
EPO (2o polycythemia),
PTH-related peptide
(hypercalcemia)
Flank mass, hematuria
Invades renal vein (key
prognostic factor)

Renal cell carcinoma: yellow tumor

with clear cells containing lipid

Lytic metastases
(pathologic
fractures,hypercalemia)

RENAL TUMORS
WILMS TUMOR
MC renal tumor in children
Sporadic or AD types (WAGR: Wilms, aniridia,
genital abnormalities, retardation)
Flank mass, hypertension (due to increased ectopic
production of renin)

BLADDER TRANSITIONAL/SQUAME
Transitional: smoking, aniline dyes, cyclophosphamide
Squamous: Schistosoma hematobium (terminal spine)
Eosinophils around egg:
IgE antibodies attached
to egg. Eosinophil IgE
receptors bind to IgE and
release major basic
protein, which kills egg
(type II HSR).

PENIS SQUAMOUS CELL CARCINOMA

Lack of circumcision (smegma), HPV, +/- smoking

CRYPTOORCHIDISM (CO)
Risk for seminoma in CO testis and normally descended testis.
1st migration MIS, 2nd migration hCG + androgens

ORCHITIS
Usually unilateral in mumps (females develop oophoritis)

EPIDIDYMITIS
STD in young population. Scrotal elevation pain (Prehn sign).

VARICOCELE
Left-sided (MC): spermatic
vein empties into renal vein
(pressure on spermatic vein
leading to varicose veins).
Can be caused by renal cell
carcinoma invading the renal
vein.
Right-sided: retroperitoneal
fibrosis. Inferior vena cava
thrombosis.

Bag of worms

Common cause of
infertility (excess heat
inhibits spermatogenesis on
affected and unaffected
side; controversial)

TESTICULAR CANCER

Painless testicular mass cancer!!! Metastasis to paraaortic nodes.

Seminoma

PROSTATE HYPERPLASIA
DHT/estrogen-induced. Periurethral location. Hyperplasia of
glands and stroma. Obstructive uropathy. Bladder
diverticula. Bilateral hydronephrosis. PSA. Does not
transform into prostate cancer.

PROSTATE CANCER
MC male cancer. DHT-induced. Peripheral location (within
range of finger in rectal exam). PSA.

Osteoblastic metastasis
Alkaline phosphatase

Non-disjunction meiosis: XXY (47

chromosomes)
Testicles are small in size (volume).
Seminiferous tubules are fibrosed no
spermatogenesis (azoospermia) and no Sertoli
cells. Absence of Sertoli cells leads to
synthesis of inhibin (normal function of
Sertoli cells) and a corresponding synthesis
of FSH by the pituitary gland (inhibin has a
negative feedback relationship with FSH).
FSH stimulates Leydig cells
and adipose to synthesis of aromatase.
Aromatase converts most of the testosterone
synthesized by Leydig cells to estradiol leading
to feminization. In addition, what little
testosterone is synthesized by the Leydig cells
cannot interact with androgen receptors
(receptor resistance), which also contributes
to feminization.
Klinefelters syndrome: Inhibin FSH aromatase. Aromatase
conversion of testosterone to estradiol.
note feminization
Testosterone causes pituitary synthesis of
(gynecomastia, female
LH.

Pages 143-144

hair distribution)

SXR inheritance: male pseudohermaphrodite (genotype is

Pages 148-149
male, but phenotype is female). In AIS, androgen
receptors are absent or non-functional. Testicles are
present (inguinal area or abdominal cavity).
Normal male fetus development: Normal
testosterone (T) function is to convert mesonephric
structures into accessory structures (seminal vesicles,
epididymis, vas deferens). Normal DHT function is to
convert female appearing structures into male
structures. The clitoris is converted into a penis and
labia are converted into a scrotum. DHT also develops
the prostate gland. Mullerian inhibitor substance (MIS)
is synthesized by Sertoli cells and causes apoptosis of
Mullerian structures, which in a female fetus, produce
fallopian tubes, uterus, cervix, and upper vagina. The
lower 2/3rds of the vagina is derived from the
urogenital sinus.
In AIS, absent receptors prevent T and DHT
effects on the male fetus. Therefore, there are no
male accessory structures and external genitalia remains
female. The vagina ends as a blind pouch because the
urogenital sinus is not of Mullerian origin. Levels of T
Androgen insensitivity
and DHT are normal. Estradiol is slightly increased.
syndrome (AIS;
Patients are usually reared as females. Testicles are
testicular feminization)
removed because of a risk for seminoma.