Download Acute Pyelonephritis

DISEASES AFFECTING
TUBULES AND
INTERSTITIUM
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Tubulointerstitial Nephritis
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Causes :
1- bacterial infection.
2- drugs.
3- metabolic disorders such as hypokalemia.
4- physical injury such as irradiation.
5- viral infections.
6- immune reactions.
TIN is divided into :
1-acute
2-chronic
Acute Pyelonephritis
• a common suppurative inflammation of the
kidney and the renal pelvis.
• bacterial infection.
• important manifestation of (UTI) :
1- lower UT (cystitis, prostatitis, urethritis).
2- upper UT(pyelonephritis).
3- both.
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• Pathogenesis
• The principal causative organisms are :
1- Escherichia coli >is the most common .
2- Proteus.
3- Klebsiella.
4- Enterobacter.
5- Pseudomonas.
6- Staphylococci and Streptococcus faecalis (uncommon).
Routes of infection
• 1-hematogenous (seeding of the kidneys by bacteria in
septicemia or infective endocarditis)
• 2-ascending infection (most common): from the lower
urinary tract
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bladder urine is sterile and remains so as a result of:
1- the antimicrobial properties of the bladder mucosa.
2- the flushing action associated with periodic voiding of urine.
The first step is adhesion of bacteria to mucosal surfaces →
colonization of the distal urethra → bladder by expansive
growth of the colonies and by moving against the flow of urine.
Predisposing factors
1-urethral instrumentation, including catheterization and
cystoscopy
2-female sex because of the close proximity of the urethra to the
rectum
3-trauma to the urethra
4-outflow obstruction or bladder dysfunction (benign prostatic
hyperplasia; uterine prolapse; neurogenic bladder dysfunction
• 5-Pregnancy.
• 4% to 6% of pregnant women develop bacteriuria sometime
during pregnancy and
20% -40% of these eventually develop UTI.
• 6-UTI is increased in diabetes because of the increased
susceptibility to infection.
• 7-vesicoureteral reflux
An incompetent vesicoureteral orifice allows the reflux of
bladder urine into the ureters &allows bacteria to ascend the
ureter into the pelvis.
- present in 20% to 40% of young children with UTI
1- congenital defect that results in incompetence of the
ureterovesical valve.
2-acquired in spinal cord injury and with neurogenic bladder
dysfunction secondary to diabetes
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Acute pyelonephritis.
The cortical surface is
studded with focal
pale abscesses
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Drug-Induced Interstitial Nephritis
• Two forms of TIN caused by drugs are :
• 1-Acute Drug-Induced Interstitial
Nephritis
• 2-Analgesic Nephropathy
• Acute TIN
• 1-most frequently occurs with synthetic penicillins
(methicillin, ampicillin)
• 2- other synthetic antibiotics (rifampin), diuretics
(thiazides)
• 3- nonsteroidal anti-inflammatory agents
• 4-other drugs (phenindione, cimetidine
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• Pathogenesis
• Many features of the disease suggest an immune
mechanism.
• Clinical evidence of hypersensitivity is not dose
related.
• Serum IgE levels are increased in some persons
suggesting type I hypersensitivity.
• The mononuclear or granulomatous infiltrate,
together with positive skin tests to drugs, suggests
a T cell-mediated (type IV) hypersensitivity
reaction.
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Morphology
• the interstitium shows pronounced edema and infiltration by
mononuclear cells, lymphocytes and macrophages .
• Eosinophils and neutrophils may be present, often in large
numbers.
• With some drugs (e.g., methicillin, thiazides, rifampin),
interstitial non-necrotizing granulomas with giant cells may be
seen.
• The glomeruli are normal except in some cases caused by
nonsteroidal anti-inflammatory agents.
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Clinical course
• The disease begins about 15 days (range 2-40 days) after
exposure to the drug.
• It is characterized by fever, eosinophilia & rash in about 25%
of persons, and renal abnormalities.
• Renal findings include hematuria, minimal or no proteinuria,
and leukocyturia (sometimes including eosinophils).
• A rising serum creatinine or acute renal failure with
oliguria develops in about 50% of cases, particularly in
older patients.
• It is important to recognize drug-induced renal failure,
because withdrawal of the offending drug is followed by
recovery although it may take several months for renal
function to return to normal
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Analgesic Nephropathy
• Consumption large quantities of analgesics may cause
chronic interstitial nephritis often associated with renal
papillary necrosis.
• Although at times ingestion of single types of analgesics has
been incriminated, most people who develop this nephropathy
consume mixtures containing some combination of phenacetin,
aspirin, acetaminophen, caffeine, and codeine for long periods.
• Aspirin and acetaminophen
• While they can cause renal disease in apparently healthy
individuals preexisting renal disease seems to be a
necessary precursor to analgesic-induced renal failure
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• Pathogenesis
• not entirely clear.
• Papillary necrosis is the initial event, and the interstitial
nephritis in the overlying renal parenchyma is a secondary
phenomenon.
• covalent binding and oxidative damage Acetaminophen
• inhibition of prostaglandin synthesis aspirin
• Morphology
• The papillae show coagulative necrosis
• dystrophic calcification may occur in the necrotic areas.
• tubular atrophy, interstitial scarring, and inflammation.
• The small vessels in the papillae and urinary tract submucosa
exhibit characteristic PAS-positive basement membrane
thickening.
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Clinical Course
• Chronic renal failure, hypertension, and
anemia.
• The anemia results in part from damage to red
cells by phenacetin metabolites.
• A complication of analgesic abuse is the
increased incidence of transitional-cell
carcinoma of the renal pelvis or bladder in
persons who survive the renal failure.
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Acute Tubular Necrosis (ATN)
• ATN is a clinicopathologic entity characterized
morphologically by damaged tubular epithelial cells and
clinically by acute suppression of renal function.
• It is the most common cause of acute renal failure.
• In acute renal failure, urine flow falls within 24 hours to
less than 400 mL/day (oliguria).
• Other causes of acute renal failure include :
(1) severe glomerular diseases manifesting as RPGN.
(2) diffuse renal vascular diseases such as microscopic
polyangiitis and thrombotic microangiopathies.
(3) acute papillary necrosis associated with acute
pyelonephritis.
(4) acute drug-induced interstitial nephritis.
(5) diffuse cortical necrosis
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ATN is a reversible renal lesion.
predisposing clinical settings:
ischemic ATN is associated with shock
1- severe trauma.
2- acute pancreatitis.
3- septicemia.
4- mismatched blood transfusions and other hemolytic
crises, as well as myoglobinuria.
nephrotoxic ATN
poisons including heavy metals (e.g., mercury)
organic solvents (e.g., carbon tetrachloride)
drugs such as gentamicin and other antibiotics, and
radiographic contrast agents.
• Pathogenesis
(1) tubular injury
(2) persistent and severe disturbances in blood flow resulting
in diminished oxygen and substrate delivery to tubular cells.
• Tubular epithelial cells are particularly sensitive to anoxia and
are also vulnerable to toxins.
• Ischemia causes numerous structural alterations in epithelial
cells
• Loss of cell polarity reversible early event.
• Redistribution of membrane proteins (e.g., Na+, [Kgr ]+ATPase) from the basolateral to the luminal surface of tubular
cells
• Decreased sodium reabsorption by proximal tubules and hence
increased sodium delivery to distal tubules.
• Vasoconstriction.
• Redistribution or alteration of integrins that anchor tubular
cells to their underlying basement membranes results in
shedding of tubular cells into the urine