Tubulo-Interstitial Disease
Acute
Tubular
Necrosis
Ischeamic
Causes
1.
Hypovolumic
state
Tubulointerstitial Nephritis
Toxic
Causes
Exogenous
Nephrotoxin
Drug
Induced
Interstitial
Nephritis
Pyelonephritis
Endogenous
Nephrotoxin
Acute
Chronic
Acute
Urate
Nephropathy
Chronic
Acute Uric
Acid
Nephropathy
2. ↓CO output
state
3. Systemic
Vasodilation
4. DIC
5. Renal
vasoconstricti
on
1.
Obstruction
1.
Aminoglycosides
1.
Myoglobinuria
2. Amphotericin B
2.
Hemoglobinuri
a
Radiogrpahic
contrast media
4.
Immunosuppressor
3. Crystals
4. Multiple
Myeloma
2.
Anatomical
Anomalies
3.
Instrumenta
tion
4.
Immunosup
pression Tx
Reflux
Nephropathy
Chronic
Obstructive
Pyelonephritis
Acute Drug
Induced
Interstitial
Nephritis
1. Synthetic
Penicilin
2. Rifampicin
3. Thiazide
diuretic
4. NSAIDs
5. Allopurinol
6. Cimetidine
Chronic Uric
Acid
Nephropathy/
Gouty
Nephropathy
Analgesic
Nephropathy
1. Aspirin
2.
Acetaminophen
3. Phenacetin
1.Pateints
with
Lymphoma
and
Leukemia
undergoing
Chemo
1. Gouty
Arthritis
Hypercalceamic
Nephropathy
Nephrocalcino
sis
1.
Hyperparat
hyroidism
2. Multiple
Myeloma
3. Vit D
intoxificatio
n
4.
Metastatic
bone
disease
5. Milk-alkali
syndrome
Clinical Features
Acute Tubular Necrosis
Chracterized by

Rapid destruction of tubular
epithelium

Rapid reduction in urine output
o
<400ml per day

The most common cause of
Acute Renal Failure in renal
category
The Initiation Phase

Acute decrease in GFR to a
very low level

Sudden increase in
o
Serum creatinine
o
Blood Urea Nitrogen (BUN)
The Maintenance Phase

Sustained severe reduction
in GFR

Sustained increase in
o
Serum creatinine
o
BUN

Continues for a period of
time, usually 1-2 weeks
The Recovery Phase

Increase in urine ouput
o
Happens when Oliguria
present during
Maintenance Phase

Gradual decrease in
o
Serum crearinine
o
BUN

Restoration of tubular
function
Pathogenesis

o
o

o
o
o
o
Prognosis

o
o

o
o
o
Motality rate 50%
60% mortality rate in pts
with

Shock due to sepsis

Severe burn

Multiorgan failure
30% mortality rate in pts
due to Nephrotoxic
agents
Patient can recover if
doesn’t develop organs
failure during the course
50% may have some renal
impairment
5% have decline in renal
function
5% never recover kidney
function and require
dialysis

o
o
o
Tubular epithelium is highly
sensitive towards
Hypoxia
Chemical irritants
Ischeamia can cause
Depletion in ATP due to lack
of O2
Increased in cytosolic level of

Calcium

Free radical formation

Metabolism in
membrane phospholipid
metabolism
Abnormalities in cell volume
regulation
Consequently will lead to

Disruption in

Cell volume
regulation

Electrolyte regulation

Ineffective membrane
transport

Cell swollen

Intracellular
accumulation of

Calcium

Sodium
Nephrotoxic agents can cause
Intrarenal vasoconstriction
Direct toxicity to tubular cells
Intratubular obstruction
Gross

o
o

Morphology
Microscopy
Kidney appears
Pale
Swollen
Congested
medullary
parenchyma

o
o
o

o
o
o
o

o
o
o
General feature
Ragged tubular
epithelium
(necrosis)
Interstitial
edema
Tubular cast
present in urine
Ischeamic ATN
Patchy tubular
necrosis
Straight Proximal
Tubule is the
most susceptible
Rupture of
basement
membrane
(Tubulorrhexis)
Tubular casts
Nephrotoxic ATN
Uniform
involvement of
tubular segment
Sparing of distal
tubule
Preservation of
basement
membrane
Laboratory Investigation






Blood Urea and Serum Electrolyte (BUSE)
Complete Blood Count (CBC)
Full Blood Count (FBC)
Urine Full Examination Microscopy Elements
(UFEME)
Urine Sample (US)
Renal Biopsy (rarely needed)
Complication

o
o
o
o
o

o

o

o
o
o

Electrolytes
Abnormalities
Hypekaleamia
Hyponatreamia
Hypermagneseamia
Hypocalceamia
Hyperphosphateamia
Intravascular Volume
Overload
May lead to Pulmonary
Edema
Hypertension
Due to salt and water
retention
Ureamic Syndrome
Precardial disease
GIT upsets
Neurological symptoms
Metabolic Acidosis
Epidemiology
Acute
Pyelonephritis
Chronic
Risk Factors

Female

Pregnancy

Urinary tract obstruction
o Benign Prostatic
Hypertrophy
o Tumor
o Calculi
o Neurogenic bladder
o Pre-existing renal lesion
with intrarenal scarring

Anatomical anomalies
o Vesicoureteral Reflux

Instrumentation
o Catetherization
 Immunosuppression Tx

Chronic tubulointerstitial
inflammation

Renal scarring with
pathologic involvement of
o Calyces
o Pelvis

Can be categorized in 2
o Reflux Nephropathy

Common

Can be either

Unilateral

Bilateral
o Chronic Obstructive
Nephropathy

Obstruction leads to

Parenchymal
atrophy

Can be either

Unilateral
o Calculi

Bilateral
o Obstructive
anomalies of UT
Pathogenesis
Acending
infections
o Due to reflux
of
pathogens
against the
flow of the
urine
o ‘can be due
to
 Vesicoure
teral
reflux
 Intrarenal
reflux
 Heamatogeno
us spread of
bacteria
secondary to
bactereamia

Morphology
Gross
Microscopic
 Cortical
 Acute inflammatory
surface can
exudate within
have
o Tubule
o Grayish
o Intrarenal
white area
interstitium
of
 Intratubular
inflammati
aggregates of
on
Neutrophils
o Abscess
o Leukocyte cast
formation
in the urine
 Patchy interstitial
suppurative
inflammation
Surface is
irregular
 Cut surface
o Dilated
calyces
o Blunted
calyces

Focal/ extensive
chronic
inflammation with
interstitial fibrosis
 Tubules are
o Atrophic
o Dilated
 Thyroidization
happens due
to dilated
tubules
containing
Eosinophilic
Proteinaceous
Material

Clinical Features
Loin/back/ flank pain
Systemic evidence of
infection
o Fever
o Malaise
 Bladder and Urethral
irritation
o Urgency
o Frequency
o Dysuria
 Urinalysis
o Pyuria
 Urine with many
leukocytes
o Leukocytes casts
 Idicator of renal
involvement


Complications (ACUTE)





Endotoxic shock/
Septiceamia
Papillary necrosis
Perinephric abscess
o Invasion of
inflammation from the
renal capsule to
perinephric tissue
Pyonephrosis
o Suppurative exudate in
 Pelvis
 Calyx
 Ureter
o Due to total/ partial
obstruction
Fibrosis
o Distortion of shape and
function
Epidemiology

Acute DrugInduced Interstitial
Nephritis
Adverse effects of
certain Nephrotoxic
drugs such as
o
Methicillin

Trigger
interstitial
immunologica
l response
o
Gentamicin

Directly cause
ATN
o
Analgesic abused

Subtle but
cumulative
tubular injuries
Pathogenesis
Drugs bind covalently with
cytoplasmic and extracellular
components of tubular cells

These complex then become
Immunogenic

The injury happens due to IgE/
cellular immune mediated
response to
o
Tubular cells
o
Basement membrane

Gross
Morphology
Microscopic
Hardly seen any gross
changes on the kidneys


o
o

o
o


o
o
Interstitial edema and
inflammation
Infiltration of
Lymphocytes
Macrophages
Large number of
Eosinophils
Neutrophils
Small number of
Basohils
Tubulitis
Intratubular
epithelial
Lymphocytes
Tubular

Necrosis

Regeneration
Clinical Features


o
o
o
o
o

o
o
Drug-Induced
Interstitial
Nephritis


o
o
o
o

Analgesic
Neuropathy
(Chronic)
Women>men
Prevalent in pts
with
Recurrent
headache
Muscle pain
Psychoneurotic
Factory workers
These subjects
often abuse
analgesics

o
o

o

o
o
o
Analgesic mixture can cause
damage to kidney through
Renal papillary necrosis
Chronic tubulointerstitial nephritis
Phenacetin metabolite and
Acetaminohen
Injures the cells through

Covalent binding that elicits
immune response

Oxidative stress
Aspirin
Inhibits vasodilatory effects of
Prostaglandin

Leads to Papillary ischeamia

End up with Coagulative
Necrosis
Children

Cause the Minimal Change
Disease

Maybe due to injury to
Podocytes by cytokine during
inflammation
Adults

Cause Membranous
Glomerulonephritis

Causes remain unknown


o
o
o
o

o
o
Kidney appears
smaller or normal in
size
Renal papilae
Various stages of
necrosis
Calcification
Fragmentation
Sloughing
Renal cortex
Depressed/
atrophic
Raised areas

o
o

o
o
o
o
Renal cortex
Loss and atrophy of
tubules
Interstitial fibrosis
and inflammation

Due to
obstruction by
damaged
tubular cells in
the papillae
Renal papillae
Early

Patchy papillary
necrosis
Advanced

Entire papillary
necrosis
Ghosts of tubules –
coagulative
necrosis
Foci of calcification

o
o

o
o
Begins about 15 days
after exposure to drugs
Characterized
Fever
Transient Eosinophilia
Rash
Renal abnormalities

Heamaturia

Mild proteinuria

Leukocyturia
In older patients

Acute renal failure

Increased serum
creatinine
Withdrawal of the
offending drugs is
followed by recovery
May take several
months
Irreversable damage
often happens in
elderly
Findings
Early

Inabality of kidney
to concentrate
urine
Late

Distal tubular
acidocis

Renal stone
Clinical Features
Early

Headache

Aneamia

GIT symptoms

Hypertension

UTI (50%)
Later

Heamaturia

Renal colic

Due to
obstruction of
tubule by necrotic
papillae