Infection of the Urinary Tract and Kidney
Describe the histological changes that are present in Chronic Pyelonephritis
*Interstitial inflammation and fibrosis *Tubules are either atrophied or flattened *Chronic inflammatory infiltrate (macrophages, plasma cells, lymphocytes) replaces the neutrophils of Acute Pyelonephritis *Thyroidization *Glomeruli are usually spared but may lead to FSGS *Aside from Thyroidization, the other changes are nonspecific and can be seen in any chronic renal disorder causing interstitial damage
Xanthogranulomatous Pyelonephritis
*Rare form of chronic pyelonephritis *Characterized by granulomatous tissue with lipid laden foamy macrophages *Often associated with Proteus, Klebsiella, or Pseudomonas infections resulting from obstruction from kidney stones *May produce large, yellow/orange nodules (mass lesion); often confused for RCC **Almost always unilateral*
Chronic Pyelonephritis
*Result of recurrent episodes of acute pyelonephritis *Chronic infection is likely due to VUR present from childhood (reflux type), and/or chronic distal obstruction (e.g., BPH) causing hydronephrosis (obstructive type). *Gross: Corticomedullary Scarring (diffuse or at poles) and Caliectasis *Histological: Interstitial fibrosis and inflammation, Atrophied and flattened tubules, Thyroidization of some tubules *Gradually progresses to renal insufficiency *Tx:
Hemorrhagic Cystitis
*Results from damage to the bladder's transitional epithelium *Presentation :Frequency, dysuria, urgency, suprapubic discomfort, microscopic and gross hematuria *Can be due to infectious causes or due to pelvic radiation or from toxicity to certain chemotherapy *Adenovirus = MCC of acute hemorrhagic cystitis in children *Cyclophosphamide, ifosfamide = MCC of pharmacological hemorrhagic cystitis
List 4 reasons why Women are more predisposed to Urinary Tract Infections
*Shorter length of urethra *Prostatic fluid has antibacterial properties *Urethral trauma during sex *
Acute Pyelonephritis
*Suppurative, patchy inflammation of the renal interstitium and pelvis *Often is preceded by/ is a complication of cystitis/urethritis *More common in women (becomes more common in older men due to BPH) *Presentation: Suprapubic pain, dysuria, urinary frequency, urgency *Systemic signs (eg, high fever, chills) are usually absent *MCC = E.Coli *Lab findings: Leukocytosis, positive urine culture *Tx: *Uncomplicated acute pyelonephritis follows a benign course and symptoms disappear in few days after antibiotic therapy *Suspect complications if patient is symptomatic after 5 days
Describe the Clinical Presentation of Renal Papillary Necrosis
*Typically bilateral (as many of the predisposing causes are systemic) *Uncommon in individuals younger than 40 (except in those with sickle cell, hypoxia, septicemia) *Fever and chills *Flank and/or abdominal pain *Hematuria *Rarely may result in ARF with oliguria
Name 4 risk factors that predispose to Pyelonephritis
*Vesicoureteral reflux => reflux into the bladder and increased residual volume. VUR is almost always present in patients with pyelonephritis . *Urinary Tract Obstruction => increased residual volume and stasis (prostatic hypertrophy, tumors, neurogenic bladder dysfunction from diabetes/spinal cord injury *Immunosuppresion/Immunodeficiency: Increased risk of hematogenous spread *Pregnancy
Tubulointerstitial Nephritis can be acute or chronic. What histological features can distinguish between the two?
Acute: Neutrophils and Eosinophils in infiltrate, interstitial edema Chronic: Lymphocytes, Macrophages, and Plasma Cells in infiltrate, Interstitial fibrosis, Tubular atrophy
What type of casts are seen in the urine of patients with acute pyelonephritis? chronic pyelonephritis?
Acute: WBC casts Chronic: Eosinophilic, hyaline casts
Acute pyelonephritis is predominated by a neutrophilic infiltrate. What type of inflammatory cells eventually replace the neutrophils and are present in Chronic pyelonephritis/
Acute: predominantly neutrophilic Chronic: predominantly macrophages, plasma cells, lymphocytes
What antibiotics are indicated in the treatment of acute pyelonephritis?
why not TMPsmz
What mnemonic can we use to remember the drugs associated with Acute Interstitial Nephritis?
Please Note All Drugs that Can Possibly Scar Renals -*P*enicillin derivatives (e.g. methicillin, ampicillin) -*N*SAIDs -*A*llopurinol -Sulfa-derived *D*iuretics (e.g. thiazides, furosemide, acetazolamide) -*C*ephalosporins -*P*roton pump inhibitors -*S*ulfonamide antibiotics & Sulfasalazine -*R*ifampin—RNA polymerase inhibitor used to treat TB
Why are pregnant women more susceptible to urinary tract infections and resulting pyelonephritis?
Pregnancy results in relaxation of the basal tone of the ureteral smooth muscle (due to increased progesterone). This ureteral dilation or physiologic hydronephrosis increases urine pooling and in turn the risk of ascending infection
A 52-year-old woman comes to the physician because of a 2-day history of fever and left flank pain. She has been treated for multiple episodes of pyelonephritis during the past 3 years. Her temperature is 37.8°C (100.1°F). Physical examination shows left flank tenderness. Urinalysis shows 12-18 WBC/hpf with occasional lymphocytes and mononuclear cells with features of macrophages. Cultures of urine grow 80,000 colonies/mL of Proteus mirabilis. An x-ray of the abdomen shows a 3-cm mass in the lower pole of the left kidney. Gross examination of the mass after it has been resected shows that it is yellow, 3.2-cm in diameter, and centrally but not marginally necrotic. Histologic examination of the mass shows a predominance of epithelioid cells with partially clear and granular-to foamy cytoplasm. Nuclei are eccentric, normochromic, symmetric, and without significant pleomorphism. Scattered lymphocytes and plasma cells are intermixed. Which of the following is the most likely diagnosis? (A) Acute pyelonephritis (B) Malacoplakia (C) Renal cell carcinoma, clear cell type, intermediate grade (D) Renal cell carcinoma, granular cell type (E) Xanthogranulomatous pyelonephritis
(E) Xanthogranulomatous pyelonephritis
Acute Interstitial Nephritis
*AKA Tubulointerstitial Nephritis (inflammation of tubules and interstitium) *Goljan says MCC is Acute Pyelonephritis *Other sources say MCC is hypersensitivity to certain Drugs *A wide variety of causes: Drugs, Heavy metals, systemic diseases * *
Drug-Induced Interstitial Nephritis
*Acute inflammation of renal interstitium (edema + prominent mononuclear and eosinophilic infiltrate) *Abrupt onset of signs and symptoms about 15 days (range of 2-40 days) after the first dose of the inciting drug *Resolves following withdrawal of drug (may take months) **Drug acts as a hapten* *Type I OR Type IV hypersensitivity (immune response is critical to the disease pathogenesis) **Development of drug-induced AIN is not dose-related* *Classic triad of signs of renal injury + Fever, Rash, and Eosinophilia is only seen in 10% *Urine microscopy may show WBCs (pyuria), RBCs (hematuria), WBC casts, and Eosinophils (eosinophiluria; highly suggestive but not always present or specific) *Tx: Corticosteroids
Match the feature with the appropriate UTI causing organism *Ammonia odor *Blue-green pigment *Produces urease *Swarming on agar *Fruity odor *Red pigment
*Ammonia odor: Proteus mirabilis *Blue-green pigment: Pseudomonas aeruginosa *Produces urease: Klebsiella, Proteus mirabilis *Swarming on agar: Proteus mirabilis *Fruity odor: Pseudomonas aeruginosa *Red pigment: Serratia marcescens
What are the two mechanisms by which bacteria can reach the kidney? Which is more common? Which types of organisms are more commonly associated with each?
*Ascending Infection *Hematogenous Infection *Ascending infection is far more common. Hematogenous infection is seen mainly in immunosuppressed and severely debilitated patients Ascending: E. Coli, Proteus Hematogenous: S. Aureus; M. Tuberculosis
Malakoplakia
*Associated with chronic E.coli or occasionally Proteus infection of the bladder *Associated with a defect in phagocyte function *More common in immunocompromised (HIV/renal transplant recipients) *Gross: soft, yellow, slightly raised mucosal plaques *Histology: Foamy epithelioid histiocytes with PAS+ granular eosinophilic cytoplasm *Macrophages contain Michaelis Gutmann bodies: basophilic laminated structures; defective phagosomes containing non-digested bacteria
Describe the histological changes that are present in Renal Papillary Necrosis
*Characteristic coagulative infarct necrosis, with preserved tubule outlines
Only two diseases are known to cause damage to the renal calyces. What are they?
*Chronic Pyelonephritis *Analgesic Nephropathy This makes calyceal damage an important diagnostic clue
Name four complications of Acute Pyelonephritis
*Chronic Pyelonephritis *Renal Papillary Necrosis *Perinephritic abscess: Pus around kidneys (in perinephric space) *Septicemia
Renal Papillary Necrosis
*Coagulative necrosis of the renal medullary pyramids and papillae *Causes sloughing of renal papillae *Considered a sequela of ischemia occurring in the renal papillae and the medulla **Produces gross hematuria, proteinuria, and flank pain* *Primarily a bilateral process *Remember the causes using the mnemonic SO sAAD *An IVP shows a "ring defect" where one or more papillae used to reside. CT will show bumpy contours *Never involves the cortex; limited to the medulla
Compare presentation of Cystitis and Pyelonephritis
*Cystitis: WBCs in urine. Absence of casts *Pyelonephritis: WBCs in urine. WBC or eosinophilic casts *Cystitis: Urinary frequency, urgency, hesitancy, dysuria, hematuria, suprapubic pain; Lack of systemic symptoms *Pyelonephritis: Triad of Fever/chills; Flank pain (CVA tenderness); Nausea/vomiting; Symptoms of cystitis may or may not be present
Describe the histological changes that are present in Acute Pyelonephritis
*Extensive infiltrate of neutrophils present in the collecting tubules and interstitial tissue (may form microabscesses or neutrophilic casts) *Glomeruli are typically spared
What lab findings are seen in patients with acute pyelonephritis?
*Hematuria (typically microscopic) *Pyuria (WBCs) and often WBC casts *Peripheral blood smear showing leukocytosis (>11,000 /mm3) *Positive urine culture (Positive in almost 100% of patients)
Cystitis
*Inflammation of the urinary bladder *Results from retrograde spread of colonic bacteria in most cases *Typically precedes pyelonephritis * * * * *
Describe the histological changes seen in Acute drug-induced interstitial nephritis
*Interstitial edema *Interstitial infiltrate consisting primarily of T lymphocytes and monocytes;Eosinophils, plasma cells, and neutrophils also may be found. *"Tubulitis" is found when inflammatory cells invade the tubular basement membrane
A 26-year-old male currently undergoing standard therapy for a recently diagnosed active tuberculosis infection develops sudden onset of fever and oliguria. Laboratory evaluations demonstrate high levels of eosinophils in both the blood and urine. Which of the following is most likely responsible for the patient's symptoms: 1. Rifampin 2. Isoniazid 3. Pyrazinamide 4. Ethambutol 5. Return of active tuberculosis symptoms secondary to patient non-compliance with anti-TB regimen
1. Rifampin This presentation is consistent with acute drug-induced tubulointerstitial nephritis (TIN). Acute drug-induced TIN occurs as a combined type I and type IV hypersensitivity reaction 1-2 weeks after administration of certain drugs: Beta-lactam antibiotics (penicillin), rifampin, sulfonamides, NSAIDs, and diuretics. The rifampin component of the standard anti-TB regimen of isoniazid, rifampin, and pyrazinamide is most likely responsible for the onset of symptoms seen in this patient. Acute drug-induced TIN is associated with sudden onset of fever, oliguria, rash, as well as eosinophilia/eosinophiluria (key clinical finding that is predictive of acute drug-induced TIN) and a BUN:Cr ratio of less than 15. In this disease, the offending drug acts as a hapten to elicit a combined type I/IV hypersensitivity reaction that can manifest 1-2 weeks after initiation of the agent. Typical treatment is to withdraw administration of the drug
A 22-year-old sexually active female presents to the emergency department in severe pain. She states that she has significant abdominal pain that seems to worsen whenever she urinates. This seems to have progressed over the past day and is accompanied by increased urge and frequency. The emergency room physician obtains a urinalysis which demonstrates the following: SG: 1.010, Leukocyte esterase: Positive, Protein: Trace, pH: 7.5, RBC: Negative. Nitrite: Negative. A urease test is performed which is positive. What is most likely cause of UTI in this patient? Topic Review Topic 1. Klebsiella pneumoniae 2. Staphylococcus saprophyticus 3. Proteus mirabilis 4. Escherichia coli 5. Serratia marcescens
2. Staphylococcus saprophyticus Note that in infection with S. saprophyticus, nitrites would be negative as this is a gram positive organism.
A 45-year-old female presents to the emergency department with gross hematuria and acute, colicky flank pain. She denies any previous episodes of hematuria. She reports taking high doses of acetaminophen and aspirin over several weeks due to persistent upper back pain. The patient's blood pressure and temperature are normal, but she is found to have proteinuria. Physical examination is negative for palpable flank masses. Which of the following is the most likely diagnosis: 1. Diffuse cortical necrosis 2. Chronic pyelonephritis 3. Autosomal dominant polycystic kidney disease 4. Papillary necrosis 5. Acute Nephrolithiasis
4. Papillary necrosis Acute onset of gross hematuria, colicky flank pain, and proteinuria are characteristic of renal papillary necrosis. Papillary necrosis is caused by the sloughing of necrosed renal papillae into the urinary space. It is associated with several diseases that prompt ischemia of the renal papillae, including analgesic nephropathy, sickle cell disease or trait, diabetes mellitus, and acute pyelonephritis. Overuse of non-steroidal anti-inflammatory drugs (NSAIDs) causes analgesic nephropathy by decreasing prostaglandin synthesis, leading to constriction of the glomerular afferent arteriole.
A 60-year-old man with a history of osteoarthritis has been awaiting hip replacement surgery for 3 years. During his annual physical, he reports that no amount of analgesic can relieve his constant pain. Laboratory results reveal that his renal function has deteriorated when compared to his last office visit 2 years ago. Serum creatinine is 2.0 mg/dL and urinalysis shows 1+ proteinuria. There are no abnormalities seen on microscopy of the urine. A renal biopsy shows eosinophilic infiltration and diffuse parenchymal inflammation. What is the most likely explanation for this patient's deterioration in renal function? Topic Review Topic 1. Focal segmental glomerulosclerosis 2. Ischemic acute tubular necrosis 3. Nephrotoxic acute tubular necrosis 4. Toxic tubulointerstitial nephritis 5. Rapidly progressive glomerulonephritis
4. Toxic tubulointerstitial nephritis The question stem describes a patient who is overusing analgesics. In this scenario, the most likely explanation for deterioration in renal function is NSAID-induced toxic tubulointerstitial nephritis (TIN). Ischemic ATN would present with muddy-brown/granular casts on urine microscopy, as a result of reduced blood flow to the kidneys
A 60-year-old man with a history of osteoarthritis has been awaiting hip replacement surgery for 3 years. During his annual physical, he reports that no amount of analgesic can relieve his constant pain. Laboratory results reveal that his renal function has deteriorated when compared to his last office visit 2 years ago. Serum creatinine is 2.0 mg/dL and urinalysis shows 1+ proteinuria. There are no abnormalities seen on microscopy of the urine. A renal biopsy shows eosinophilic infiltration and diffuse parenchymal inflammation. What is the most likely explanation for this patient's deterioration in renal function? 1. Focal segmental glomerulosclerosis 2. Ischemic acute tubular necrosis 3. Nephrotoxic acute tubular necrosis 4. Toxic tubulointerstitial nephritis 5. Rapidly progressive glomerulonephritis
4. Toxic tubulointerstitial nephritis The question stem describes a patient who is overusing analgesics. In this scenario, the most likely explanation for deterioration in renal function is NSAID-induced toxic tubulointerstitial nephritis (TIN). As a mechanism of renal injury, NSAIDs decrease prostaglandin synthesis, resulting in ischemic damage to the kidney by decreasing afferent arteriole dilation that is mediated by prostaglandins. Additionally, NSAIDs uncouple oxidative phosphorylation in renal mitochondria, causing direct oxidative damage. Bakris et al. report that as a result of widespread availability and misuse, NSAIDs have become a common cause of acute renal failure. The clinical presentation of NSAID-associated TIN differs from that of antibiotic-associated TIN in that proteinuria is much more common with NSAID-associated TIN, while eosinophilia, eosinophiluria, fever and rash are more common with antibiotic-associated TIN.
A 78 year old male currently receiving treatment for malignant lymphoma reports to the ER complaining of pain when urinating and hematuria. The patient hands a list of medications he is on to the ER physician. What is the most likely drug responsible for this man's urinary symptoms? A - Cyclophosphamide B - Doxorubicin C - Vincristine D - Prednisolone E - Rituximab
A - Cyclophosphamide Cyclophosphamide is a common chemotherapeutic agent used to treat lymphoma, breast cancer, ovarian cancer, and multiple myeloma. It is the C in the CHOP therapy acronym. Cyclophosphamide is a nitrogen mustard that works by alkylating DNA and preventing replication in rapidly growing tissues such as cancers. The most asked about side effect of cyclophosphamide is hemorrhagic cystitis, which is how the above patient presents. Cyclophosphamide is metabolized to acrolein, a very caustic unsaturated aldehyde. Acrolein accumulates in the urine and causes hemorrhage of the bladder wall. The most common initial presentation will be microscopic hematuria, dysuria, and increased urinary frequency before evolving to gross hematuria. Treatment for hemorrhagic cystitis is twofold: 1) Mesna which neutralizes acrolein and 2) ample fluid intake to dilute urinary acrolein.
A 51-year-old male had a "neurogenic bladder", caused by a spinal cord tumor. He had multiple bladder infections which were treated with antibiotics. He had surgery to remove the tumor. Postoperatively, he developed fever and costovertebral angle tenderness which did not respond to antibiotics. He expired and an autopsy was performed. What is your diagnosis? A) Acute pyelonephritis B) Acute glomerulonephritis C) Chronic pyelonephritis D) Chronic glomerulonephritis ALL of the following are risk factors for this condition EXCEPT: A) Reflux nephropathy B) Congenital vesicoureteral reflux C) Posterior urethral valves D) Acetaminophen (Paracetamol)overdose E) Urolithiasis
A) Acute pyelonephritis D) Acetaminophen (Paracetamol)overdose
A 23-year old woman at 32 weeks gestation comes to the emergency department because of a 1-day history of left flank pain and fever. Her temperature is 39.1 C (102.3F). Pulse is 104/min, respirations are 14/min, and blood pressure is 120/72 mm Hg. Physical examination shows prominent tenderness over the left costovertebral angle. A photomicrograph of a renal biopsy specimen from a similar patient is shown. Which of the following is the most likely diagnosis? A) Acute pyelonephritis B) Acute renal infarction C) Acute tubulointerstitial nephritis D) Crescentic glomerulonephritis E) Hemolytic uremic syndrome
A) Acute pyelonephritis Biopsy: Neutrophilic infiltrate present in the collecting tubules and interstitial tissue + CVA tenderness + fever + pregnant woman
What is the mechanism by which acetaminophen and aspirin cause papillary damage in analgesic nephropathy?
Acetaminophen: metabolism depletes cells of glutathione, an antioxidant, thereby leaving cells susceptible to free radical damage. Aspirin: inhibits PGE2, thereby reducing the vasodilatory effect of prostaglandins on the afferent arteriole and leaving the papillae susceptible to ischemia (unopposed AGII)
A previously healthy 19-year-old woman comes to the medical clinic because of severe abdominal pain for the past 18 hours. She has had increasingly frequent painful urination over the past 24 hours. She is not sexually active. Temperature is 38.5 C (101.3 F), pulse is 90/min, respirations are 14/min, and blood pressure is 115/76 mm Hg. The suprapubic area is tender on palpation. Microscopic examination of urine shows pyuria, hematuria, and bacteriuria. Which of the following organisms is the most likely cause of these symptoms? A) Chlamydia trachomatis B) Escherichia coli C) Neisseria gonorrhoeae D) Pseudomonas aeruginosa E) Staphylococcus aureus
B) Escherichia coli E.Coli = MCC. Even if the patient were sexually active, the answer would still be E.Coli rather than Staphylococcus saprophyticus—
A 35-year-old woman presents to her gynecologist with complaints of burning on urination for the past 2 days. Dipstick test of her urine demonstrates marked positivity for leukocyte esterase, but no reactivity for nitrite. Urine culture later grows out large numbers of organisms. Which of the following bacteria are most likely to be responsible for this patient's infection? A. Enterobacter sp. B. Enterococcus faecalis C. Escherichia coli D. Klebsiella pneumoniae E. Pseudomonas aeruginosa
B. Enterococcus faecalis The positive leukocyte esterase test indicates the presence of neutrophils in the urine, suggesting a bacterial infection. The nitrite test exploits the fact that most Enterobacteria (gram-negative enteric rods) are able to form nitrite from nitrate; thus, the nitrite test is used to diagnose urinary tract infections. One limitation of this method is the fact that enterococci (gut streptococci) do not produce nitrite from nitrate, but can nonetheless cause urinary tract infections. Enterococcal urinary tract infections are often nosocomial and classically acquired in the intensive care unit, although they can occur in other settings. Enterobacter sp. (choice A), Escherichia coli(choice C), Klebsiella pneumoniae(choice D), and Pseudomonas aeruginosa(choice E) can cause urinary tract infections and would usually be picked up by the dipstick for nitrites. False-negative results might still be seen with these organisms if the infection was light, the bladder had been recently emptied prior to collection, and the urine was "new" and had not yet grown enough bacteria to produce a positive result
A 20-year-old woman is found to have a blood pressure of 140/100 mm Hg at a routine annual examination. Fasting serum studies show a urea nitrogen concentration of 50 mg/dL and glucose concentration of 90 mg/dL. Urinalysis shows numerous WBCs and WBC casts; protein excretion is 3000 mg/24 h(N<150). The estimated glomerular filtration rate is 20% of normal. Ultrasonagraphy shows small asymmetric kidneys with broad scars and blunted calyces, and voiding cystourethrography shows a vesicouretreral reflux. Which of the following is the most likely diagnosis? A) Acute glomerulonephritis B) Bilateral hydronephrosis C) Chronic pyelonephritis D) Diabetic nephropathy E) Renal amyloidosis
C) Chronic pyelonephritis Broad scars + blunted calcyes + VUR on cystourethrography = Chronic pyelonephritis VUR = MCC of Chronic pyelonephritis
An 87 year old woman with severe dementia is brought to the physician because of fever, chills, lethargy, and agitation for 2 days. her temperature is 38.3 C (101 F). examination shows tenderness of the lower abdomen and right costovertebral angle. Laboratory studies show: Leukocyte count ...................... 18,000/mm3 ---Segemented neutrophils ..... 65% -- Bands .................................... 20% -- Lymphocytes ........................ 15% Urine -- RBC ........................................ 20/hpf -- WBC ....................................... 50/hpf -- Granular casts ...................... Positive -- Bacteria ................................. Few Which of the following is most likely diagnosis? A) Allergic interstitial nephritis B) Glomerulonephritis C) Pyelonephritis D) Retroperitoneal abscess E) Tubular necrosis
C) Pyelonephritis
A 52-year old woman with a long history of intermittent urinary symptoms underwent a cystoscopy. A biopsy of the yellow mucosal plaques revealed the presence of chronic inflammatory cells with numerous histiocytes, some of which contained small intracytoplasmic spherical structures. The most likely diagnosis is: A. Cystitis cystica B. Polypoid cystitis C. Malacoplakia D. Eosinophilic cystitis E. Transitional cell carcinoma
C. Malacoplakia Malacoplakia is chronic inflamatory coondition of the bladder characterized by the presence of numerous histiocytes, some of which contain small intracytoplasmic inclusions called Michaelis-Gutmann bodies.
How do drugs trigger a hypersensitivity reaction in acute drug-induced interstitial nephritis?
Drug acts as a hapten by covalently binding to a carrier (e.g., an extracellular or cytoplasmic protein of renal tubular cells). Most drugs are too small to induce immune responses by themselves. The hapten-carrier conjugate serves as an immunogen, triggering a hypersensitivity reaction (Type I and/or Type IV), thereby inducing injury of tubular cells and/or their basement membrane.
Describe the clinical presentation of Acute Pyelonephritis
Fever and chills Flank pain (CVA tenderness) Nausea/vomiting Symptoms of cystitis may or may not be present (urinary frequency, urgency, hesitancy)
What is the classic triad of signs seen in Drug-Induced Interstitial Nephritis
Fever, Rash, and Eosinophilia
Name two drugs that can cause Hemorrhagic Cystitis Name a virus that often causes Hemorrhagic Cystitis in children
Cyclophosphamide, ifosfamide Adenovirus (Serotypes 11&21)
Cystitis = inflammation of the _______________ Pyelonephritis = inflammation of the ______________
Cystitis: Bladder Pyelonephritis: Kidney
On autopsy, a pathologist notes a similar finding between the kidneys of two separate patients. One patient was a diabetic while the other patient had sickle cell anemia. Which of the following could be found in the kidneys of both patients? A) Corticomedullary scarring B) Diffuse calcium deposition C) Numerous petechial hemorrhages D) Papillary necrosis E) Hydronephrosis
D) Papillary necrosis
An 83-year-old woman is seen by the physician at home because of increased confusion for the past 24 hours. She has a 7-year history of dementia, Alzheimer type, that has reached an advanced stage. Her temperature is 37.8* C (100 F), pulse is 116/min, respirations 36/min, and blood pressure is 85/60 mm Hg. Physical examination shows decreased alertness and clouding of the lenses bilaterally but is otherwise unremarkable. Laboratory studies show: Leukocyte count: 20,5000/mm3 Urinalysis WBC: 50/hpf RBC: 30/hpf Protein: 100 mg/dL Despite treatment, her blood pressure continues to decrease and she dies 24 hours later. Renal tissue obtained from the autopsy is shown. Which of the following is the most likely diagnosis? A) Hemolytic-uremic syndrome B) Good pasture syndrome C) Hepatorenal syndrome D) Pyelonephritis E) Rapidly progressive glomerulonephritis F) Renal tuberculosis
D) Pyelonephritis Biopsy: Neutrophilic infiltrate present in the collecting tubules and interstitial tissue Elderly patients may present with typical manifestations of pyelonephritis, or they may experience fever, mental status change Severe cases of pyelonephritis lead to sepsis, a systemic response to infection characterized by fever, a raised heart rate, rapid breathing and decreased blood pressure (occasionally leading to septic shock). When pyelonephritis or other urinary tract infections lead to sepsis, it is termed urosepsis.
A 41-year-old white male presents to ER with fever and chills, for the past 2 days. His fever was gradual in onset and is associated with back pain, which is worse towards the sacral area. He is also having repeated urges to urinate, along with pain on micturition. His rectal examination reveals a boggy exquisitely tender prostate. You find organisms that are lactose fermenters and turn pink in MAC agar. On urethra, examination reveals yellow nodules which contain concentrically layered basophilic inclusions found microscopically. What do these inclusions contain? Why?
Dx: Malakoplakia Malakoplakia is a rare chronic inflammatory disease which commonly affects the urogenital tract Gross: soft, yellow, slightly raised mucosal plaques The presence of Michaelis Gutmann bodies (basophilic laminated structures) is pathogenic. These bodies contain non-digested bacteria as the condition is thought to be due to a defect in phagocyte function
A 5-year-old boy is brought to the physician 1 hour after urinating bright red blood. He has been taking ibuprofen since injuring his right flank while wrestling with friends yesterday; he also has been taking penicillin for 3 days for streptococcal pharyngitis. His temperature is 36.7 C (98 F), blood pressure is 90/48mm Hg, pulse is 108/min, and respirations are 18/min. Examination shows purple ecchymoses over the shins and right flank; there is tenderness of the right costovertebral area. The abdomen is nontender. Genital examination shows no abnormalities. There is no edema. Urinalysis shows gross blood; microscopic examination shows 5-10 leukocytes/hpf and erythrocytes that are too numerous to count. Which of the following is the most likely explanation for this patient's hematuria? A) Acute pyelonephritis B) Ibuprofen-induced acute papillary necrosis C) Post-streptococcal glomerulonephritis D) Rhabdomyolysis E) Traumatic injury to the kidney
E) Traumatic injury to the kidney Althought the presentation is very similar to renal papillary necrosis, in healthy individuals in whom real arterial blood flow is not compromised, NSAIDS have little effect unless they are used in excess. This is mostly true because the kiney is not relying on the vasodilatory effects of prostaglandin to supply adequate perfusion However, in paients who are predisposed to renal hypepoperfusion, local prostaglandinsynthesis protects the glomeruli and tubules form ischemia. (NSAIDS inhibit COX1&2 and inhibit this pretective mechanism and can result in ischemia in those with predisposing risk factors : Elderly, heart failure, prior renal disease). Furthermore, the the typical patient is age 50 and RPN is uncomon in individuals < 40 and in children (unless they have sickle cell, hypoxia, other risk factors). As this patient doesn't have any risk factors and is not in the appropriate age group, RPN is unlikely PSGN is unlikely because it typically occurs 2 - 3 weeks after infection Traumatic injury to the kidney can also result in hematuria and flank pain
A 22-year-old primigravid woman at term is admitted to the hospital in labor. Her pregnancy has been complicated by three urinary tract infections; the last episode occurred at 22 weeks' gestation. She is now taking daily nitrofurantoin. She is otherwise healthy .Which of the following is the most likely cause of this patient's recurrent urinary tract infections? A) Decreased urinary pH during pregnancy B) Hypotonic environment in renal medulla C) Increased sodium excretion D) Increased urinary bladder tone E) Urinary stasis
E) Urinary stasis Pregnancy results in relaxation of the basal tone of the ureteral smooth muscle (due to increased progesterone). This ureteral dilation or physiologic hydronephrosis increases urine pooling and in turn the risk of ascending infection
A 26 year-old woman comes to the physician because of 2-year history of recurrent episodes of cystitis that are associated with sexual intercourse. Her symptoms began after she married her husband. Vital signs are normal. Physical examination and urinalysis show no abnormalities. Which of the following practices is most likely to decrease the frequency of these infections? A) Douching on a weekly basis B) Drinking 8 ounces of fluids immediately prior to intercourse C) Having her husband use a condom D) Using a diaphragm for contraception E) Voiding soon after intercourse
E) Voiding soon after intercourse Voiding after intercourse reduces the risk for infection by washing out bacteria in the urethra.
A 24-year old female with no past medical history presents to her primary care doctor complaining of a fever. The fever started two days ago, though she was unable to take temperatures at home and has just felt "hot." Review of systems is positive for fatigue, arthralgia, and decreased urine output in the last day or so. She recently completed a course of trimethoprim-sulfamethoxazole for an uncomplicated urinary tract infection. Vital signs are temperature 101.3F, heart rate 104 bpm, blood pressure of 114/74, and respiratory rate of 18. Physical exam is significant for a diffuse, non-pruritic maculopapular rash on the torso, but is otherwise normal. Lab studies show the following: Sodium 141 mEq/L Potassium 4.4 mEq/L Chloride 99 mEq/L Bicarbonate 23 mEq/L BUN 30 mg/dl Creatinine 2.1 mg/dl Glucose 102 mg/dl Urinalysis shows pyuria w/many eosinophils and no bacteria. What is the most likely etiology of this patient's chemistry abnormalities? A. Decreased renal perfusion secondary to dehydration B. Post-obstructive nephropathy C. Granulomatosis with polyangiitis (Wegener's disease) D. Sloughing of tubular epithelium into the tubule E. Allergic immune response in the renal interstitium
E. Allergic immune response in the renal interstitium
Describe the gross appearance of Renal Papillary Necrosis on a cut section of the kidney
Gray-white to yellow necrosis on the tips of the pyramids
Name two gram negative organisms that are negative for nitrite?
Enterococcus faecalis Pseudomonas
In which 2 renal diseases can eosinophilic casts be seen? In which renal disease is a eosinophilic cellular infiltrate seen?
Eosinophilic casts *Multiple Myeloma *Chronic Pyelonephritis Eosinophilic cellular infiltrate *Drug-induced interstitial nephritis
What finding on Intravenous Pyelogram is characteristic of Renal Papillary Necrosis?
IVP whows "ring defect" where necrosed papilla used to reside
Do pregnant women have an increase or decreased incidence of UTI?
Increased
Describe the gross appearance of the kidney in Acute Pyelonephritis
Multiple pale-yellowish abscesses on the cortical surface
How is NSAID nephropathy different from Acute drug-induced interstitial nephritis
NSAID nephropathy is unique in that it begins after several months or years of exposure. Another unique feature of interstitial nephritis caused by NSAIDs is that patients may present with nephrotic syndrome (massive proteinuria, edema) and biopsy may show signs of minimal change disease
In Chronic Pyelonephritis, if bilateral, the kidneys are __________(symmetrically/asymmetrically) scarred In Chronic Glomerulonephritis, if bilateral, the kidneys are __________(symmetrically/asymmetrically) scarred
Pyelonephritis: Asymmetric Glomerulonephrtis: Symmetric
What findings on urinalysis are indicative of cystitis?
Pyuria (neutrophils in the urine) Bacteriuria Hematuria Positive leukocyte esterase and/or nitrite dipstick (Leukocyte esterase = indicates presence of WBCs; suggests bacterial cause) (Positive nitrite = indicates gram - organism)
What mnemonic can be used to remember the causes of Renal Papillary Necrosis? Which is the most common cause?
SO sAAD Sickle Cell Trait or Disease Obstruction of urinary tract Acute Pyelonephritis Analgesic Nephropathy (easily induced experimentally by giving aspirin and phenacetin) Diabetes Mellitus (MCC) *Generally, any condition associated with ischemia/hypoxia predisposes an individual to RPN
Name 7 common bacterial agents responsible for cystitis
SSEEK PP *S*. saprophyticus (associated with young, sexually active women) *S*erratia marcescens (some strains produce a red pigment) *E*. coli (most common) & Enterococci *E*nterobacter cloacae *K*lebsiella pneumonia *P*roteus mirabilis (swarming appearance on agar, urine smells like ammonia) *P*seudomonas aeruginosa (produces a blue-green pigment and fruity odor, usually nosocomial)
A ___________ (short/long) intravesical ureter is associated with an increased risk of VUR
Short intravesical ureter = increased risk Normally, the intravesicular portion of the ureter is compressed during urination, however with a short intravesicular ureter , the ureter is not compressed as it is more at a right angle => reflux
Thyroidization of the Kidney in Chronic Pyelonephritis
Some of the tubules in Chronic Pyelonephritis may be filled with eosinophilic casts resembling thyroid colloid (Thyroidization)
Define Sterile Pyuria. What 3 organisms are at the most likely cause of this finding?
Sterile pyuria is the presence of WBCs in the urine in the absence of a positive bacterial culture *Neisseria gonorrhoeae *Chlamydia trachomatis *Genitourinary Tuberculosis
What finding is seen on renal CT scan in patients with acute pyelonephritis?
Striated enhancement of the parenchyma
Anatomically, which section of the kidney is the papilla?
The Renal papilla is the tip of each cortical pyramid. Urine flows from the pyramid, through the papilla into the minor calyx.
What is the blood supply of the Renal Papillae?
The Vasa Recta Interlobular branches of Renal Artery Oxygen content in the renal papillae tend to be lower than in other parts of the kidney. Also rate of blood flow in the vasa recta is slow (to maintain the countercurrent mechanism). Thus, conditions that further reduce blood flow may produce frank ischemic necrosis
Describe the clinical presentation of Drug-Induced Interstitial Nephritis
The classical presentation described = Signs of Renal injury (oliguria/elevation in serum creatinine) + Triad of Fever, Rash, and Eosinophilia *The entire triad is seen in only 10% of patients; Each individually is seen in 15-25% *Flank *Urine microscopy may show WBCs (pyuria), RBCs (hematuria), WBC casts, and Eosinophils (eosinophiluria; highly suggestive but not always present or specific)
Pyelonephritis characteristically causes scarring in which part of the kidney? Explain why this occurs
The greatest number of scars are seen in the upper and lower poles This is consistent with the increased frequency of reflux occurring at these sites -These peripheral papillae are concave/flat and permit the entry of refluxed urine -Central papillae are convex/pointed and don't allow reflux of urine
What is the most common location for the cortical scars seen in patients with chronic pyelonephritis?
The poles of the kidney
Describe the gross morphological appearance of the kidney in Chronic Pyelonephritis
The two characteristic gross changes in Chronic pyelonephritis are *Corticomedullary scarring (depressed areas) an Caliectasis (dilation/blunting of the calices) If Chronic Pyelonephritis is due to VUR, then the scarring is characteristically at the poles. If it is due to chronic obstruction the scarring is more diffuse and cortical thinning is also present
Acute drug-induced interstitial nephritis is caused by what type(s) of hypersensitivity reaction?
Type I OR Type IV *Some patients have increased serum IgE levels, suggesting Type I *Others mononuclear/granulomatous infiltrate on renal biopsy and positive skin tests to drugs, suggesting Type IV
Patients with analgesic nephropathy are at increased risk of developing what cancer?
Urothelial (transitional cell) carcinoma of the renal pelvis.
What is the most common cause of chronic pyelonephritis?
Vesicoureteral abnormalities with subsequent reflux
What radiological procedure can be used to diagnose Vesicoureteral Reflux (VUR)?
Voiding Cystourethrogram Real time video x-ray procedure that uses contrast material to examine how well the bladder is voiding urine
A 48-year-old woman with a 20-year history of chronic headaches suddenly develops right ipsilateral colicky abdominal pain with radiation into the right groin. She has been taking aspirin and phenacetin for the headaches. She shows no signs of fever. Urinalysis shows red blood cells (RBCs), white blood cells (WBCs), and mild proteinuria. There are no bacteria, casts, or crystals. Urine specific gravity is 1.010 and remains unchanged the following morning. An intravenous pyelogram shows a ring deformity in the right kidney. What is the most likely cause of the damage to her kidney? a) Ascending infection b) Hypersensitivity c) Ischemia d) Obstruction to urinary passage e) Vasculitis
c) Ischemia The patient has renal papillary necrosis, which is a chronic, drug-induced tubulointerstitial nephritis (analgesic nephropathy) caused by ingestion of aspirin and acetaminophen over many years. Aspirin inhibits renal production of prostaglandin E2, which is a vasodilator of the afferent arteriole, leaving angiotensin II, a vasoconstrictor of the efferent arteriole, in control of the blood flow into the peritubular capillaries. The resultant sloughing of the renal papillae into the urine causes the patient's right-sided colicky pain. The ring deformity in the right kidney on the intravenous pyelogram indicates absence of the renal papillae.
