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The tubular cells of the nephron secrete a protein into the filtrate called the Tamm-Horsfall protein. This protein
is excreted by the thick ascending branch of the loop of Henle and the first part of the distal tubules. This
protein accounts for the normal daily loss of approximately 100 mg of protein from the kidney. Even under
normal circumstances, this protein can polyermize or congeal as it makes its way through the nephron, and on
congealing, conform to the shape of the nephron, thereby coming out as cylindrical molds of the tubes they are
in. These molds are called casts. In a normal person these casts of pure Tamm-Horsfall protein are called
hyaline casts and most of the time, their presence does not signify any pathology. When there are cells present
in the filtrate (which is always an abnormality), the Tam-Horsfall proteins will congeal around these cells to
form a mold, or cast which consequently emerge. These cells could be RBCs, WBCs, or epithelial cells
sloughing off. In glomerulonephritis, the glomerulus is inflamed and the capillaries that constitute the
glomerulus are damaged allowing the RBCs to leak out of it. The RBCs are molded into the shape of the
tubules, resulting in RBC casts. The presence of certain casts has very specific interpretations: Hyaline casts: I
(renal 5) present even in healthy people, especially after exercise/sweating when the urine is concentrated and
acidic, predisposing to Tamm-Horsfall polymerization. RBC casts: I (renal 5). Pathognomonic of nephritic
form of glomerulonephritis. Also occurs in severe tubular damage. WBC casts: I (renal 5) are most typical for
acute pyelonephritis, but they may also be present with glomerulonephritis. Their presence indicates
inflammation of the kidney, because such casts will not form except in the kidney. Waxy casts: I (renal 6) This
slide shows a pale cast with sharp margins. This represents a waxy cast. Waxy casts are the end stage of
breakdown of coarse and finally granular casts and they are classic for chronic renal failure. Broad cast in
chronic renal failure: I (renal 6)The cast is broad owing to tubular dilatation from obstruction of the lumens
by casts. Fatty casts: I (renal 5) Fatty casts or oval fat bodies are associated with nephrotic syndromes because
a patient typically has hypercholesterolemia.*The very first thing that happens when you get renal failure is the
ability of the kidney to concentrate urine. Thus if we take a specific gravity of a persons urine take in the
morning after waking up, and find that it is normal, we know hes not in renal failure.*Calcium oxalate
crystals: I (renal 6) Calcium oxalate and/or phosphate crystals are the most common type of crystal found in
the urine. They are independent of urine pH for formation. They appear like an unfolded envelope. They are
associated with hypercalcemia states and commonly accompany calcium oxalate stones. Additional causes
include Crohn's disease, excessive intake of vitamin C, and ethylene glycol poisoning. Uric acid crystals: I
(renal 6) Scattered stellate or star-shaped crystals which are classic for uric acid crystals. These crystals form in
acid urine. They are seen in states where there is a high rate of turnover of cells as in leukemias or lymphomas
or multiple myeloma. They can also be seen in gout. Cystine crystals: I (renal 6) Note the hexagonal shape. It
occurs in the AR disorder called cystinuria and can be associated with cystine stones.

Page 243
Nomenclature of the glomerular disease:
If ends in itis, its a type III
hypersensitivity problem. So
glomerulonephritis is type III
hypersensitivity disease, but
glomerulosclerosis is not. Diffuse
disease: when we do a biopsy and every
single glomerulus is diseased. Focal
disease: when not all the glomeruli are
diseased. When we have a focal disease,
and only certain parts of the glomerulus
is disease, we could say it was focal
focal, but that sounds too close to a rude
word (ha ha), so we call that focal
segmental. Proliferative. The word
indicates lots of something. So when we
have lots of nuclei in the glomerulus, its
called proliferative. Membranous. When
we look at the glomerulus and dont see
nuclei, but lots of membranes.
Membranoproliferative: When we see
lots of nuclei and membranes in the
glomerulus.
On the back of the add-on given below
The glomerular capillaries are surrounded by the Bowmans capsule
that has visceral and parietal epithelial membranes. The visceral part
is made up of podocytes, which interdigitate to form thin filtration
slits. The podocytes
also produce the
basement membrane.
The basement
membrane has a
strong negative charge
that keeps the albumin
out of the filtrate. This
negative charge is due
to heparan sulfate
(not heparin!). If the
visceral epithelial
cells (i.e., the
podocytes) are damaged, the basement membrane will also be
knocked off, which means that albumin will start to leak through.

Page 242
Tests that we do on a renal biopsy in evaluating glomerulonephritis: (i) we
do the regular, H&E stain, (ii) immunoflorescence stains. The
immunoflorescence detect antibodies, if any, that adhere to glomerulus. The
patterns with which the antibodies adhere are characteristic for different
disease. Such stains could be linear, or they could be granular (the so-called
lumpy-bumpy appearance). We also have stains for different antibodies, e.g., a
different stain for IgA, IgM, Complement, etc (iii) electron microscopy: This
shows us exactly where the antibodies are located, and also shows us if the
podocytes are fused. **Often times, glomerular diseases are caused by the
deposition of immune complexes. These immune complexes will be of various
sizes. Immune complexes that are quite large dont get very far, depositing just
underneath the endothelial cells (subendothelial deposits). Other immune
complexes are quite small and manage to get past the basement membrane only
to get stuck underneath a podocyte. These deposits are called subepithelial
deposits. The exact location of the deposits, i.e., subendothelial vs.
subepithelial helps the diagnosis because any given disease deposits in either
one of the two places. The location of these deposits is discerned with electron
microscopy. Note however, that these immune-complex deposits will never
have linear pattern on immunoflorescent stains because they go ahead and
deposit randomly. When we see a lack of a linear pattern in
immunoflorescence, it could be any glomerulonephritis other than
Goodpastures syndrome. The only other time (other than Goodpastures) that
we can definitively diagnose the type of glomerulonephritis from the
immunoflorescence alone is in the case of IgA glomerulonephritis. In that case
the diagnosis will be simple because the immunoflorescent stain wed be using
would be only for IgA. Thus, immunoflorescence, if showing a linear pattern
will diagnose that we have Goodpastures syndrome, or if it stains with IgA
immunoflorescent markers will diagnose IgA glomerulonephritis. All other
patterns will be of the lumpy bumpy pattern and will require electron
microscopy to clinch the diagnosis. Also note that such lumpy bumpy
patterns always means immune-complex deposits (type III hypersensitivity).
Page 243
There are two types of glomerulonephritis: Nephritic and Nephrotic.
A nephritic type can evolve to become nephrotic. The features that
distinguish these two types are: Nephritic syndrome: Has a unique
cast, the RBC cast. This is only found in the nephritic form of
glomerulonephritis. Because there is inflammation of the glomerulus,
you are going to spill protein, but not greater than 3.5 grams (mild-tomoderate proteinuria). If there were more than 3.5 grams of protein in
the urine, it would be, by definition, nephrotic syndrome. The
inflammation of the glomerulus will se the GFR and wed get
oliguria. This causes an sed retention of Na+, because not enough is
being filtered out, which results in hypertension. Thu in nephritic
syndrome we have: RBC casts, oliguria, mild-to-moderate protienuria,
hypertension In nephrotic syndrome, we have a fatty cast (not an
RBC cast), greater than 3.5 grams of protein in the urine and thirdly,
pitting edema and ascites. None of these 3 things are found in
nephritic syndrome. The glomerulonephropathies either cause
nephritic or nephrotic syndrome. The key to dealing with the
glomerulopathies is to remember which ones cause which type of
syndrome. You must be able to recognize nephritic and nephrotic
syndromes by the clinical picture and after deciding which one it is,
draw up the list of glomerulopathies that causes that particular
syndrome. Each glomerulopathy causing a syndrome has unique
clinical and morphological features that help identify it. There is
usually no concept to these features and you will have to just brute
force memorize them to deal with the questions they ask regarding
them.
Page 250
The pathology that eventually causes severe renal
damage in diabetics is the preferential hyaline
arteriolosclerosis of the efferent arterioles. This causes
the glomerulus to take quite a pounding, that over
years can destroy it. The reason why ACE inhibitors
are reno-protective in diabetics is that the angiotensin,
which constricts the efferent arteriole, is blocked. This
relieves the pressure gradient b/w the efferent and
afferent arterioles and thus relieves the pounding
that the glomerulus was subjected to. Note that the
afferent arteriole is not constricted by angiotension,
but by PGE2, and so an ACE inhibitor will not affect
it. Diabetics frequently also have HTN, and so giving
an ACE inhibitor will also take care of that problem.
Note though that the ACE inhibitor does not address
the pathogenesis of the renal damage, i.e., the nonenzymatic glycosylation of proteins, so it not going to
be effective for very long in a patient with poor
glycemic control.

Page 244
Bergers disease is quite common and doesnt fall neatly into
either a nephritic or nephrotic grouping. It could present as
either one. It is thought that Bergers disease is a variant, if not
the same thing as Henoch-Schonleins purpura.
Immunoflourence will show the complexes in the mesangium.
In kids it presents as episodic bouts of gross hematuria. It goes
away and might come back a couple years later. In adults it
usually presents as episodic bouts of microscopic hematuria. It
comes and goes, comes and goes Eventually, over 10-20
years, it can cause severe renal damage.
Page 239

BUN and Creatinine are both filtered at

the glomerulus. Of the two, urea is
partially reabsorbed at the PCT, while
creatinine is not. The normal
BUN:Creatinine concentration ratio is
about 10:1. In pre-renal azotemia
(azotemia means sed BUN), the cause is
always a se in CO. Anything that causes
a se in CO comes under this category.
This causes the GFR to se, which
allows the PCT to reabsorb a little bit
more BUN than it normally would
because the filtrate is flowing past at a
slower speed. Creatinine is not
reabsorbed, at any speed, but since there
is less of it coming in, there is less of it
being excreted, so the Creatinine will
also se, but not as much as BUN.
Hence, in prerenal azotemia, we have a
disproportionate se in BUN compared
to Creatinine, and an sed BUN:Cr ratio
(> 15:1). eg, a patient in CHF might have
a BUN of 80 and Creatinine of 2. The
ratio is 40:1 and the diagnosis is prerenal
azotemia. Post-renal azotemia: In renal
failure, the BUN and Creatinine are both
elevated proportionately because neither
are being excreted, e.g., a we can have a
BUN of 80 and a creatinine of 8. Both
levels are way over their normal range,
but the ratio is maintained at 10:1,
leading to a conclusion that the patient
has renal failure. In heart failure, the sed
CO can cause ischemic injury to the
kidneys and result in ischemic acute
tubular necrosis, which means the
kidneys die as a result of a lack of blood.
The MCC of ischemic ATN is CO.
Note that in such cases, the azotemia
may first have a pre-renal picture, but if
the situation does not improve, the
picture could soon turn into a renal
azotemia.
Page 251

In ischemic ATN, there is not

enough blood going to the kidney.
Tubular cells slough off and clog
the nephron resulting in azotemia.
The prognosis of ischemic necrosis
is bad when the basement
membrane is messed up too. While
the tubular cells can regenerate,
without a basement membrane,
any attempt at regeneration will be
futile because the cells wont be
able to align themselves into a
shape of a tubule. Thus if the
damage extends all the way down
to the basement membrane, that
nephron is render useless forever.
If the damage is limited to the cells
of the tubules, then that nephron
will be able to regenerate. The
more nephrons with damaged
basement membranes, the worst
off the prognosis for that kidney.

Page 252 upper left

All UTIs begin at the urethra. The E.Coli (the
same one found in stool) makes its way from the
stool, to the anus, to the introitus of the vagina. All
women have this E.Coli there, and it has nothing to
do with cleanliness. In some women, the E. Coli
makes it way to the urethra and can go one to
become a urethritis, cystitis, and if there is a
vesicoureteric reflux, it can also cause a
pyelonephritis.*
Page 258
In a UTI, we can expect to see neutrophils, RBCs
and bacteria. A dipstick can pick up all 3 of these
things. There is a portion to the dipstick that picks
up RBC, another that picks up WBCs, etc
Hematuria is a common feature of UTIs, and in
some cases of cystitis can even be hemorrhagic.
The dipstick also has a portion for leukocyte
esterase (which will be positive in the presence of
neutrophils). Most urinary pathogens are nitrate
reducers which mean they can reduce nitrate into
nitrite. The dipstick also has a portion that detects
nitrite (E Coli will be + for this). The symptoms of
UTIs are: Dysuria, sed frequency, supra-pubic
pain. This symptoms, when correlated with +
dipstick findings for WBCs/leukocyte esterase,
RBCs, nitrites will confirm a UTI. The next step is
to assess if its upper or lower: Fever, flank pain,
WBC casts are all features of upper UTI. These
are all absent in lower UTIs (i.e., cystitis on
down). In some people, we can have all the
symptoms and dipstick findings of a UTI, but on
microscopy, we wont see a single bug, and the
nitrite will be negative as well. This occurs in
Chlamydia, which is not picked up on standard
cultures (in men it causes non-specific urethritis,
and women, the acute urethral syndrome). This
situation where we have WBCs, but no visible
bugs on microscopy is called sterile pyuria. Its not
really sterile, of course, its just that we dont see
the bug on standard microscopy or cultures. This
occurs with Chlamydial. It also occurs in milary
TB infections (the most common organ that milary
TB goes to is the kidney).

Page 252, next to chronic pyelonehpritis

Chronic pyelonephritis is renal injury induced
by recurrent or persistent renal infection. It
occurs almost exclusively in patients with
major anatomic anomalies, including urinary
tract obstruction, struvite calculi, renal
dysplasia, or, most commonly, vesicoureteral
reflux (VUR) in young children.
Page 253, top left, next to the text
The number of drugs that can cause this is
actually a lot (dozens). Just learn a few of the
more notorious ones. The classic scenario will
be that youll give the drug and the patient will
develop a rash, fever and oliguria. In such a
case, you must stop the drug immediately and
never give the patient the drug again. Drug
induced tubulointerstitial nephritis is more
commonly becoming a cause of ARF in the
US.
Page 253,
The acetaminophen causes free-radical injury,
and since the medulla only gets 10% of the
blood supply, this will be the region affected
most. Concomitant use of aspirin makes
matters worse because the PGE2 is blocked,
causing angiotensin to be the main vasoactive
substance in the kidney. Angiotensin causes
constriction of the efferent arterioles, and
since the peritubular capillaries are derived
the efferent arterioles, they will get less blood.

Page 254
CRF is defined as a serum BUN:Creatinine level of
10:1 for more than 3 months. In CRF, well have a
build up of substances, like Na (causing HTN), and
urea. Erythropoietin will not be produced resulting in
normocytic anemia with corrected ret. count < 2%.
The organic acids that are normally excreted will
build up, resulting in metabolic acidosis. The bones
try to buffer all that acid, which results in
osteoporosis. There wont be activation of Vitamin D,
resulting in sed Ca2+ and sed PO4 and so
osteomalacia can also develop. The se in Ca2+ causes
PTH to se (secondary hyperparathyroidism) which
makes the bone problems even worse.
Page 264
Scenario: 75 year old man with dribbling,
urinary rentention. MCC for this is not
cancer, but hyperplasia. The reason is
that cancer develops in the outer portion
of the prostate, but BPH develops around
the peri-urethral portion. For a cancer to
cause urethral obstruction, it has to eat its
way inwards and constrict the urethra
from all sides. Its far more likely for a
BPH to do this than a cancer.