Renal Disorders

Objectives
1. Explain the difference between nephritic syndrome and nephrotic
syndrome.
2. Explain the consequences of urinary obstruction and reflux.
3. Explain the difference between azotemia and uremia.
4. List the causes and consequences of acute tubular necrosis (ATN).
5. Discuss the common causes of pre-renal, intra-renal and post-renal
acute renal failure.
6. Describe the features of chronic renal failure.
7. Name the most common type of urinary stone, and discuss some
diseases or conditions associated with it.
8. Name the most important malignancies of the kidneys.
 Outline
• Anatomy of the Kidney
• Renal System Dysfunction
– Urinary Tract Infections (UTI)
– Acute Tubular Necrosis
– Disorders of Glomerular
Filtration
– Cystic Disease
– Renal Failure
– Neoplasms of the Urinary Tract
Normal Adult Kidney
• The capsule has been removed.
• A pattern of fetal lobulations still
persists.
• The hilum at the mid left contains
some adipose tissue.
• Smooth-surfaced, small, clear fluid-
filled simple renal cysts occur either
singly or scattered around the renal
parenchyma and are not uncommon
in adults.
Normal Kidney in Cross Section
• This normal adult kidney
demonstrates the lighter
outer cortex and the
darker medulla
• Note the renal pyramids
into which the collecting
ducts coalesce and drain
into the calyces and
central pelvis.
 Renal Disorders
• Urinary tract infections (UTI)
• Acute Tubular Necrosis
• Disorders of Glomerular Filtration
• Cystic Disease
• Renal Failure
• Renal Stones
• Neoplasms of the Urinary Tract
 Urinary Tract Infections
• Cystitis
– affecting urinary bladder and ureters

• Pyelonephritis
– affecting the renal pelvis and kidney parenchyma
Routes of Renal Infection
 Cystitis
• Inflammatory condition of urinary bladder and
ureters
• Characterized by:
– Urgency
– Pain
– frequency of urination
– hematuria
Acute Cystitis

• Acute inflammation of
the bladder.
• Areas of hyperemia of
the mucosa are
visible.
 Pyelonephritis
• A diffuse infection of the renal pelvis and
parenchyma
• Acute pyelonephritis usually the result of infection
that ascends from the lower urinary tract
• E. coli is a common cause in females
• Characterized by:
– Pain in the flanks, fever, chills, nausea, urinary
frequency
Acute Pyelonephritis
• This occurs as a result of
an ascending bacterial
infection.
• Numerous
polymorphonuclear cells
(PMNs) are seen filling
renal tubules.
 Chronic Pyelonephritis

• Develops after bacterial infection of kidney

• The presence of plasma cells is characteristic of
this condition
• May progress to kidney failure
Renal Abscess
• Infections can reach the
kidney either by ascending
up the urinary tract (from a
bladder infection, for
example) or by
hematogenous spread with
sepsis.
• This could cause abscesses
typified by necrotic area
surrounded by inflamed
tissue.
Acute Tubular Necrosis -
Microscopic

• The epithelium of the

renal tubules undergoes
necrosis in acute tubular
necrosis (ATN).
 Acute Tubular Necrosis
• May be intrarenal, postrenal, prerenal
• Associated with
– Lower urine osmolality
– Elevated urine sodium
– Fractional sodium excretion increases, i.e., urine
sodium : serum sodium ratio rises
– Tubular cell casts, protein in urine
Acute Tubular Necrosis - Gross
Disorders of Glomerular Function
• These conditions:
– decrease the efficiency of filtration
– allow blood cells, lipids, or proteins to pass into the
urine
 Glomerulonephritis
• Inflammation of the glomeruli
• Etiology
– Infectious (streptococcal), autoimmune
• Cause immune-mediated damage to basement membrane
• Risks: genetics, streptococcal pharyngitis
• Manifestations:
– Decreased GFR
– Leaky basement membrane
Immune Damage to the Glomerulus
 Types of Nephron Dysfunction
• Nephritic syndromes
– Proliferation of cells due to inflammation.
• Nephrotic syndrome
– Increased permeability of glomerulus
 Nephritic Syndromes -
Pathophysiology
• Inflammatory process damages capillary walls in
kidney
– Red blood cells escape into the urine
• Hematuria with red cell casts
– Red cells may clog renal tubules
– Glomerular filtration rate (GFR) decreases
• Azotemia (presence of nitrogenous wastes in the blood), oliguria
• Cells in kidneys proliferate due to inflammation
– Renin-Angiotensin-Aldosterone pathway activated
– Hypertension results
 Nephritic Syndrome - Clinical
Features
• Hematuria
• Red blood cell (RBC) casts and fragmented RBCs in
urine
• Oliguria
• Proteinuria
• Hypoalbuminemia
• Edema
• Hypertension
Nephrotic Syndrome -
Pathophysiology

lipids
 Nephrotic Syndrome - Clinical
Features
• Proteinuria
• Hypoalbuminemia
• Edema, generalized
• Hyperlipidemia
• Lipiduria with lipid casts in urinary sediment
Simple Cyst of the Kidney
Cystic Disease
• Such a large renal cyst would
be seen on a radiographic
imaging procedure, but could
probably be distinguished from
a neoplasm by its uniform fluid
density and thin wall.
• Such simple cysts are unlikely
to compromise renal function.
Adult Dominant Polycystic Kidney
Disease
• The most common hereditary
kidney disease.
• Occurs in approximately 1 in
every 400 to 1000 people.
• This disease is inherited with an
autosomal dominant pattern.
– Each child of an affected parent has
a 50% chance of inheriting the
disease.
– If a patient with the disease does not
pass it along to one of his or her
children, then the disease
disappears from that family and
grandchildren cannot inherit the
disease.
Adult Dominant Polycystic Kidney
Disease
• Characterized by extensive cystic
change in the kidneys.
• The cysts are not usually present at
birth, but develop slowly over time
from kidney tubules.
• There is associated inflammation,
scarring, and apoptosis of normal
parenchyma, which reduces GFR.
• Clinical manifestations include flank
and abdominal pain, uremia,
hypertension, kidney stones, UTIs,
hematuria.
• APKD leads to kidney failure.
• The onset of renal failure occurs in
middle age to later adult life.
 Kidney Failure

When Kidneys Fail

– Less waste is removed

– More waste remains in the blood
– Nitrogenous compounds building up in the blood
include:
• Blood urea nitrogen (BUN)
• Blood creatinine
 Classification of Renal Failure
• Acute Renal Failure (ARF)
– Sudden severe decrease in renal function
– Manifested by rapidly progressing uremia (50%
mortality)
• Chronic Renal Failure (CRF)
 Acute Renal Failure
• Prerenal
– Decreased blood supply
– Caused by shock, dehydration,
vasoconstriction
• Postrenal
– Urine flow is blocked
– Caused by stones, tumors, enlarged prostate
• Intrinsic
– Kidney tubule function is decreased
– Caused by ischemia, toxins, intratubular
obstruction
 Causes of Prerenal ARF
• Inadequate blood flow to kidney
– Shock
– Trauma
– Sepsis
– Hemorrhage
– Dehydration
Causes of Intrarenal and Postrenal
ARF
• Intrarenal: nephrotoxins
• Postrenal: obstruction
– Benign Prostatic Hypertrophy (BPH)
– Stones
Stages of Acute Renal Failure
 Chronic Renal Failure

• Fewer nephrons are functioning

• Remaining nephrons must filter more. Adjust
by:
– Hyperperfusion
– Hypertrophy
 Chronic Renal Failure (CRF)
Who is at risk?
• Glomerulonephritis
• Diabetic nephropathy
• Pyelonephritis
• Polycystic kidney disease
• Nephrotoxic exposure
• Obstructive nephropathy
 Stages of Chronic Renal Failure
• 75% nephron loss: Decreased renal reserve
– No signs or symptoms
– Blood urea nitrogen (BUN),
creatinine normal
• 75%-90% loss: Renal insufficiency
– Polyuria, nocturia
– Slight increase in BUN,
creatinine
• >90% loss: End-stage failure
– Uremia
 Development of CRF
• Diminished renal reserve
– Nephrons are working as hard as they can
• Renal insufficiency
– Nephrons can no longer regulate urine density
• Renal failure
– Nephrons can no longer keep blood composition
normal
• End-stage renal disease
Chronic Renal Failure
• Kidneys are atrophic with a
thin cortex.
• About a third to half of
patients with CRF slowly
reach end stage without
significant signs or
symptoms along the way.
• A steadily rising serum
creatinine and urea nitrogen
are clues.
• Most patients will also be
hypertensive.
End-stage Renal Disease
• The end result of many renal
diseases - whether they are
renal vascular diseases,
glomerulonephritis, or chronic
pyelonephritis--is end stage
renal disease (ESRD).
• In ESRD, the kidneys are
small bilaterally.
• This condition is associated
with chronic renal failure, and
the patient's blood urea
nitrogen (BUN) and serum
creatinine continue to
increase.
 Uremia
• Refers to “urine in blood’.
• Clinical features of uremia relate to
– Failure of kidneys to remove wastes
• Renal filtering function decreases
• Wastes build up in blood
– Failure of kidney tissue to perform other functions
• Kidney metabolic functions decrease
– Decreased erythropoietin
– Decreased Vitamin D activation
 Uremia – Clinical Features
• Include
– Hypertension
– Edema
– Oliguria
– Encephalopathy
– Anemia
– Bone problems - osteodystrophy
Hypertension and Kidney Failure
• Hypertension causes a
characteristic change in renal
blood vessels and glomeruli –
nephrosclerosis.
– Benign nephrosclerosis occurs
normally with age but can occur
earlier in life if hypertension is
present.
– The kidneys are atrophic with a
rough, granular surface.
– The afferent arterioles develop
hyaline arteriosclerosis thus
glomerular blood supply diminishes
over time.
– The glomeruli develop into scar
tissue.
Malignant Nephrosclerosis
• This is a severe form of
nephrosclerosis seen in
patients with malignant
hypertension (>160/110
mm/Hg).
• The tissue changes in the
kidneys occur faster than in
benign nephrosclerosis.
• The changes activate the
renal-angiotensin-
aldosterone system causing
a vicious cycle of elevated
BP.
– Leads to onion skin hyperplasia
of afferent arterioles.
How Osteodystrophy Develops
 Urinary Tract Obstruction
• May occur anywhere along the urinary tract.
• May be unilateral or bilateral.
• Obstruction may be caused by tumors, scars,
urinary stones, infections, or prostate
enlargement.
• Obstruction or loss of ureteral peristalsis can
lead to urinary stasis and secondary renal
damage.
Consequences of Chronic Urinary
Obstruction
Hydronephrosis
• Dilation of the renal
pelvis and calyses
caused by increased
urinary pressure
• Chronic obstruction
promotes urinary
stasis, infection, renal
stone formation, and
renal atrophy.
• Most hydronephrosis
is unilateral.
• Symptoms include
painfully full bladder
and urgency.
Hydronephrosis
• Internal view of kidney
pelvis and calyces dilated
with hydronephrosis.
• The thickness of the
renal cortex is
significantly reduced.
– This reflects loss of
functional tissue, i.e.,
nephrons.
Kidney Stones
• Urinary stones (calculi,
nephrolithiasis, urolithiasis)
can form anywhere in the
urinary tract but form most
frequently in the kidney
itself.
• Mostly occur in young
adults
• Men have a higher risk of
kdney stones than women.
• Stones are classified as:
– calcium stones
– Infection stones
– uric acid stones
 Types of Urinary Stones
• Calcium stones
– About 75% of all stones
– Are hard and dark
– Form when urine is supersaturated with calcium -
blood calcium levels may remain normal.
– May be associated with hyperparathyroidism.
• Infection stones
– Occur due to urine stasis.
– Bacteria alter urine pH from acidic to alkaline.
– Stones are usually high in magnesium.
• are softer than calcium stones.
 Types of Urinary Stones
• Uric acid stones
– About 5% of stones
– Often affects patients with gout, a metabolic disease
in which there are high blood levels of uric acid.
• However, majority of uric acid stones are found in individuals
who do not have gout or high blood levels of uric acid.
Staghorn Calculus
• A renal stone too large to
pass through the tract
remains in the pelvis, molding
itself into the shape of a calyx.
• Staghorn calculi often
produce hydronephrosis and
chronic infection.
Urinary Tract Tumors
 Most Important Urinary Tract
Tumors
• Renal cell carcinoma
• Transitional cell carcinoma (urothelial
carcinoma)
• Wilms’ tumor
 Neoplasms of the Urinary Tract
• Tumors originate from epithelial cells of the
kidney or the urothelium (transitional cell lining
of the pelvis, ureter, urinary bladder, and
posterior urethra).
• Wilms’ tumor is the only one found in children;
all others are found in older adults.
• Tumors are more often malignant than benign.
 Renal Cell Carcinoma
• This is a common tumor
• No strong risk factors have been identified.
• In 5% of chronic end-stage kidney disease cases, there
will be a renal cell carcinoma.
• Tumors arise in older adults (>50 years).
• 50% survive 5 years.
Renal Cell Carcinoma
• These neoplasms are usually
slow-growing, but they can
often reach a considerable
size before detection
because there is a lot of room
to enlarge in the
retroperitoneum.
• Lost renal function is
compensated by contralateral
kidney.
• Presenting symptoms and
signs usually include flank
pain, mass effect, and
hematuria.
Renal Cell Carcinoma
 Carcinoma of the Urinary Bladder
(Urothelial Carcinoma)

• Most tumors are transitional carcinomas but may

be squamous or adenocarcinomas
• Prognosis is variable - depends on the grade
and stage of the tumor
Urothelial Carcinoma
• A presenting sign can
often be hematuria.
• Examination of urine can
reveal malignant cells
shed from the surface of
the neoplasm.
Bladder Carcinoma
Urothelial Carcinoma in the
Calyces
• The cortex and medulla are
normal, but the calyces
show focal papillary tumor
masses of urothelial
carcinoma.
• Aggressive forms may
invade the renal
parenchyma, causing
obstruction to produce
hydronephrosis.
• Hematuria is a frequent
presenting symptom
 Wilms’ Tumor
• Tumor of infancy and childhood
• Composed of immature cells.
• May be familial or bilateral in 10% cases
• Prognosis is good when surgery is combined
with chemotherapy
Wilms’ Tumor
• This small kidney contains a
lobulated tan-white mass.
• Many are now known to be
associated with genetic
defects on chromosome 11.
• The children with Wilms’
tumor usually present with
abdominal enlargement from
the mass effect.