URINARY TRACT INFECTIONS/ ACUTE PYELONEPHRITIS/ CHRONIC PYELONEPHRITIS

Acute Pyelonephritis:

- a common suppurative inflammation of the kidney and the renal pelvis, is caused by bacterial infection. - It is an important manifestation of urinary tract infection (UTI), which can involve the lower (cystitis, prostatitis, urethritis) or upper (pyelonephritis) urinary tract, or both. - the great majority of cases of pyelonephritis are associated with infections of the lower urinary tract, which are very common. - most infections of the lower urinary tract remain localized and do not spread to the kidney.

Acute and chronic cystitis

- A bladder or vesical diverticulum consists of a pouchlike evagination of the bladder wall. > Diverticula may be congenital but more commonly are acquired lesions that arise as a consequence of persistent urethral obstruction caused, for example, by benign prostatic hyperplasia. > Although most diverticula are small and asymptomatic, they sometimes lead to urinary stasis predisposing to recurrent urinary tract infections and bladder stone formation. -Cystitis takes many forms: > Bacterial cystitis is common, particularly in women; The most common etiologic agents are coliform bacteria. > Hemorrhagic cystitis may occur in patients receiving cytotoxic anti-tumor drugs, such as cyclophosphamide, and sometimes complicates adenovirus infection. > Polypoid cystitis is an inflammatory condition resulting from irritation to the bladder mucosa in which the urothelium is thrown into broad bulbous polypoid projections as a result of marked submucosal edema; Polypoid cystitis may be confused with papillary urothelial carcinoma both clinically and histologically. -Transitional epithelium lining the bladder may undergo various forms of metaplasia. - Nests of urothelium (Brunn nests) sometimes grow downward into the lamina propria. > Here, their central epithelial cells may variously differentiate into a cuboidal or columnar epithelium lining (cystitis glandularis); cystic spaces filled with clear fluid lined by flattened urothelium (cystitis cystica); or goblet cells resembling intestinal mucosa (intestinal metaplasia). - As a response to injury, the urothelium often undergoes squamous metaplasia, which must be differentiated from normal glycogenated squamous epithelium, commonly found at the trigone in women.

papillary necrosis

- A second (rare) form of pyelonephritis is papillary necrosis - has three predisposing conditions: (1) diabetes (2) urinary tract obstruction (3) sickle cell anemia. - marked by ischemic and suppurative necrosis of the tips of the renal pyramids (renal papillae). - The pathognomonic gross feature is sharply defined gray-white to yellow necrosis of the apical two-thirds of the pyramids. - One papilla or several or all papillae may be affected. - Microscopically, the papillary tips show coagulative necrosis surrounded by a neutrophilic infiltrate.

Acute drug-induced interstitial nephritis

- Acute drug-induced TIN occurs as an adverse reaction to any one of an increasing number of drugs. - It is associated most frequently with penicillins (methicillin, ampicillin), other antibiotics (rifampin), diuretics (furosemide), proton pump inhibitors (omeprazole), nonsteroidal anti- inflammatory agents, and numerous other drugs (phenindione, cimetidine, immune checkpoint inhibitors). - Clinical features consistent with a hypersensitivity reaction include latent period between drug exposure and development of lesions, eosinophilia and rash, the idiosyncratic nature of the drug reaction (i.e., the lack of dose dependence), and the recurrence of the reaction following reexposure to the same drug or others of similar structure. - Serum IgE levels are increased in some individuals, suggesting immediate (type I) hypersensitivity. - In other cases, the nature of the inflammatory infiltrate and the presence of positive skin tests to drugs suggest a T cell-mediated (type IV) hypersensitivity reaction. - The most likely sequence of pathogenic events is that the drugs act as haptens that, during secretion by tubules, covalently bind to some cytoplasmic or extracellular component of tubular cells and become immunogenic. - The resultant tubulointerstitial injury is then caused by IgE- or T cell-mediated immune reactions to tubular cells or their basement membranes. - The abnormalities in acute drug-induced nephritis are in the interstitium, which shows pronounced edema and infiltration by mononuclear cells, principally lymphocytes and macrophages. - Eosinophils and neutrophils may be present, often in large numbers. ~With some drugs (e.g., methicillin, thiazides, rifampin), T cell mediated reaction may give rise to interstitial nonnecrotizing granulomas with giant cells. - The glomeruli are normal except in some cases caused by NSAIDs, in which the hypersensitivity reaction also leads to podocyte foot process effacement and the nephrotic syndrome. - The disease begins about 15 days after exposure to the drug and is characterized by fever, eosinophilia (which may be transient), rash (in about 25% of individuals), and renal abnormalities. - Urinary findings include hematuria, minimal or no proteinuria, and leukocyturia (sometimes including eosinophils). - A rising serum creatinine or acute kidney injury with oliguria develops in about 50% of cases, particularly in older patients. - Clinical recognition of drug- induced kidney injury is imperative, because withdrawal of the offending drug is followed by recovery, although it may take several months for renal function to return to normal.

Urate nephropathy

- Acute uric acid nephropathy is caused by precipitation of uric acid crystals in renal tubules leading to obstruction of the tubules and acute renal failure. - This is associated with the tumor lysis syndrome when patients undergo initial chemotherapy, especially of leukemia or lymphoma, and breakdown of necrotic tumor cell nucleic acids generates massive amounts of uric acid, which precipitate principally in the collected ducts, where the pH is more acidic. - Chronic urate nephropathy, also known as gouty nephropathy, is caused by the formation of tophi (singular "tophus"), which are masses of monosodium urate crystals with a granulomatous foreign body giant cell reaction. - Tophi erode into the interstitium, causing obstruction in the renal papillae.

Schistosoma hematobium (schistosomal infections of the urinary tract)

- After development in the liver, these blood flukes migrate to the vesical, prostatic, and uterine plexuses of the venous circulation, occasionally the portal bloodstream, and only rarely other venules. - Large eggs with a sharp terminal spine are deposited in the wall of the bladder and occasionally in the uterine and prostatic tissues. - Those deposited in the bladder wall can break free and are found in urine. - S. haematobium occurs throughout the Nile Valley and in many other parts of Africa, including islands off the eastern coast. - It also appears in Asia Minor, Cyprus, southern Portugal, and India. - Reservoir hosts include monkeys, baboons, and chimpanzees. - Early stages of infection with S. haematobium are similar to those of infections involving S. mansoni and S. japonicum, with dermatitis, allergic reactions, fever, and malaise. - Unlike the other two schistosomes, S. haematobium produces hematuria, dysuria, and urinary frequency as early symptoms. - Associated with hematuria, bacteriuria is frequently a chronic condition. - Egg deposition in the walls of the bladder may eventually result in scarring, with loss of bladder capacity and development of obstructive uropathy. - Patients with S. haematobium infections involving many flukes frequently demonstrate squamous cell carcinoma of the bladder. -It is commonly stated that the leading cause of cancer of the bladder in Egypt and other parts of Africa is S. haematobium. ~The granulomas and pseudotubercles seen in the bladder may also be present in the lungs. - Fibrosis of the pulmonary bed caused by egg deposition leads to dyspnea, cough, and hemoptysis. - Lab Dx: > Examination of urine specimens reveals the large, terminally spined eggs. > Occasionally, bladder biopsy is helpful in establishing the diagnosis. > S. haematobium eggs may appear in stool if worms have migrated to mesenteric vessels. > Serologic tests are also available. - Tx: The drug of choice is praziquantel

condyloma acuminatum

- also known as venereal warts, are caused by HPV types 6 and 11. - These lesions occur on the penis as well as on the female genitalia. ~ They should not be confused with the condylomata lata of secondary syphilis. - Genital HPV infection may be transmitted to neonates during vaginal delivery. - Recurrent and potentially life-threatening papillomas of the upper respiratory tract may develop subsequently in affected infants. - In males, condylomata acuminata usually occur on the coronal sulcus or inner surface of the prepuce, where they range in size from small, sessile lesions to large, papillary proliferations measuring several centimeters in diameter. - In females, they commonly occur on the vulva.

Clinical Features of Acute Pyonephritis:

- After the first year of life (an age by which congenital anomalies in males commonly become evident) and up to approximately 40 years of age, infections are much more frequent in females. - Up to 6% of pregnant women develop bacteriuria some time during pregnancy, and 20% to 40% of these eventually develop symptomatic urinary infection if not treated. - With increasing age, the incidence in males rises as a result of the development of prostatic hyperplasia, which causes urinary outflow obstruction. - The onset of uncomplicated acute pyelonephritis usually is sudden, with pain at the costovertebral angle and systemic evidence of infection, such as chills, fever, nausea, malaise, and localizing urinary tract signs of dysuria, frequency, and urgency. -The urine appears turbid due to the contained pus (pyuria). -The disease usually is unilateral, and affected individuals thus do not develop renal failure. -In cases in which predisposing factors are present, the disease may become recurrent or chronic and is more likely to be bilateral. - The development of papillary necrosis is associated with a much poorer prognosis

Chronic Obstructive Pyelonephritis:

- As noted, obstruction predisposes the kidney to infection. -Recurrent infections superimposed on diffuse or localized obstructive lesions lead to recurrent bouts of renal inflammation and scarring, which eventually cause chronic pyelonephritis. -The disease can be bilateral, as with congenital anomalies of the urethra (e.g., posterior urethral valves), or unilateral, such as occurs with calculi and unilateral obstructive lesions of the ureter.

Chronic Pyelonephritis and Reflux Nephropathy:

- Chronic pyelonephritis is a clinicopathologic entity in which interstitial inflammation and scarring of the renal parenchyma are associated with grossly visible scarring and deformity of the pelvicalyceal system in patients with a history of UTI. - Chronic pyelonephritis is an important cause of chronic kidney disease. - It can be divided into two forms: chronic obstructive pyelonephritis and chronic reflux-associated pyelonephritis.

Chronic Reflux-Associated Pyelonephritis (Reflux Nephropathy):

- Chronic reflux-associated pyelonephritis is the most common cause of chronic pyelonephritis. -It results from superimposition of a UTI on congenital vesicoureteral reflux and intrarenal reflux. -Both the reflux and the attendant renal damage may be unilateral or bilateral, the latter potentially leading to chronic renal insufficiency.

vesicoureteral reflux (VUR)

- Incompetence of the vesicoureteral orifice, resulting in vesicoureteral reflux (VUR), is an important cause of ascending infection. - The reflux allows bacteria to ascend the ureter into the pelvis. - VUR is present in 20% to 40% of young children with UTI, usually as a consequence of a congenital defect that results in incompetence of the ureterovesical valve. - VUR also can be acquired in individuals with a flaccid bladder resulting from spinal cord injury or with bladder dysfunction secondary to diabetes. - VUR results in residual urine after voiding in the urinary tract, which favors bacterial growth. - Furthermore, VUR affords a ready mechanism by which the infected bladder urine can be propelled up to the renal pelvis and further into the renal parenchyma through open ducts at the tips of the papillae (intrarenal reflux).

Light chain cast nephropathy (myeloma kidney)

- Light-chain cast nephropathy is one of the causes of the renal insufficiency that occurs in half of patients with multiple myeloma. -The more Bence-Jones (light chain) proteinuria a patient has, the more likely the patient will suffer this complication of multiple myeloma. - Some immunoglobulin light chain are intrinsically toxic to epithelial cells. - In addition, Bence-Jones proteins combine with urinary Tamm-Horsfall glycoprotein under acidic conditions to form large masses that elicit a macrophage response, sometimes with multinucleated giant cells, and obstruct renal tubules. - These masses resemble amyloid, which multiple myeloma patients can also get, but they are primarily in the renal papillae, whereas renal amyloidosis is usually more in the renal cortical glomeruli. - When light chains deposit in the glomeruli, that is called light chain deposition disease. - Multiple myeloma patients also often have renal disease related to hypercalcemia and hyperuricemia. - Bence-Jones proteinuria occurs in 70% of multiple myeloma patients, but when albuminuria supervenes, think superimposed light chain deposition disease or amyloidosis.

Munchausen syndrome by proxy (MSBP)

- MSBP is a mental health problem in which a caregiver makes up or causes an illness or injury in a person under his or her care, such as a child, an elderly adult, or a person who has a disability. - Because vulnerable people are the victims, MSBP is a form of child abuse or elder abuse. - Most cases of MSBP are between a caregiver (usually a mother) and a child, but it is important to remember that MSBP can involve any vulnerable person who has a caregiver. - The caregiver with MSBP may: > Lie about the child's symptoms. > Change test results to make a child appear to be ill. > Physically harm the child to produce symptoms. - Victims are most often small children. - They may get painful medical tests they don't need. - They may even become seriously ill or injured or may die because of the actions of the caregiver. - Children who are victims of MSBP can have lifelong physical and emotional problems and may have Munchausen syndrome as adults (a disorder in which a person causes or falsely reports his or her own symptoms). - What are the clues? > Checking a child's medical records for past tests, treatments, and hospital stays may help a doctor or nurse find out if a health problem is real. - Suspect a problem when: > A child has a repeated or unusual illness, and no reason can be found. > The child doesn't get better, even with effective treatments. > Symptoms only occur when the caregiver is with or has recently been with the child. > But symptoms get better or go away when the caregiver is not there or is being closely watched. > The other parent (usually the father) is not involved in the child's treatment, even though the child's condition may be serious. > A caregiver suddenly changes doctors and lies about prior testing and treatment. > Normal test results don't reassure the caregiver. And he or she may be strangely calm or happy when the child's condition is getting worse > The caregiver is seen (or videotaped or recorded) harming the child or causing symptoms. Another child in the family has had unexplained illness or death. > Urinary tract infections could be induced by instrumentation by the caregiver, such as pushing a thermometer up the urethra

Clinical Features of chronic pyelonephritis:

- Many patients with chronic pyelonephritis come to medical attention relatively late in the course of the disease, because of the gradual onset of renal insufficiency or because signs of kidney disease are noticed on routine laboratory tests. - In other cases, the renal disease is heralded by the development of hypertension. - The radiologic image is characteristic: affected kidneys are asymmetrically contracted, with some degree of blunting and deformity of the calyceal system (caliectasis). - The presence or absence of significant bacteriuria is not particularly helpful, as its absence does not rule out chronic pyelonephritis. -If the disease is bilateral and progressive, tubular dysfunction leads to an inability to concentrate the urine (hyposthenuria), manifested by polyuria and nocturia. - As noted earlier, some individuals with chronic pyelonephritis or reflux nephropathy ultimately develop secondary glomerulosclerosis, associated with proteinuria; eventually, these injuries all contribute to progressive chronic kidney disease.

Hypercalcemia and nephrocalcinosis

- Nephrocalcinosis is often confused with nephrolithiasis by medical students, which can be used by multiple choice tricksters. - Nephrocalcinosis is calcium deposition in renal parenchyma (tissue). - Nephrolithiasis is renal stones. - Stones are in the urine, formed or forming, and flushing them out is a treatment strategy. - Calcium deposits in the tissue cannot be similarly flushed out. - the conditions causing nephrocalcinosis often simultaneously cause nephrolithiasis. - Nephrocalcinosis is usually diagnosed by radiologic imaging in a patient who is found to have chronic kidney disease, often after presenting with vague symptoms, in contrast to nephrolithiasis, which is most often found in patients who present with renal colic. - Nephrocalcinosis is more often associated with a serious biochemical abnormality like hypercalcemia due to primary hyperparathyroidism, while nephrolithiasis frequently occurs in otherwise healthy individuals. - The earliest functional defect from nephrocalcinosis is an inability to concentrate the urine, which causes polyuria and nocturia. - Later, renal tubular acidosis or salt-losing nephropathy can occur as well.

Nongonococcal Urethritis and Cervicitis

- Nongonococcal urethritis (NGU) and cervicitis are the most common forms of STD. - A variety of organisms are implicated in the pathogenesis of NGU and cervicitis, including C. trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum. - In the United States, most cases are caused by C. trachomatis, and this organism is believed to be the most common bacterial cause of STD in the United States. - Mycoplasma genitalium is a close second as a cause of NGU. -The frequency of causative agents varies geographically and in certain patient populations such a men having sex with men. -In almost 50% of the cases world wide no pathogen can be identified. - gonorrhea infection frequently is accompanied by chlamydial infection.

Morphology of Chronic Pyelonephritis

- One or both kidneys may be involved, either diffusely or in patches. -Even when involvement is bilateral, the kidneys are not equally damaged and therefore are not equally contracted. -This uneven scarring is useful in differentiating chronic pyelonephritis from the more symmetrically contracted kidneys associated with vascular sclerosis (often referred to as benign nephrosclerosis) and chronic GN. - The hallmark of chronic pyelonephritis is scarring involving the pelvis or calyces, or both, leading to papillary blunting and marked calyceal deformities.

morphology of kidneys in pyelonephritis

- One or both kidneys may be involved. - The affected kidney may be normal in size or enlarged. - Characteristically, discrete, yellowish, raised abscesses are grossly apparent on the renal surface. - They may be widely scattered or limited to one region of the kidney, or they may coalesce to form a single large area of suppuration.

histologic feature of acute pyelonephritis

- The characteristic histologic feature of acute pyelonephritis is liquefactive necrosis and abscess formation within the renal parenchyma. - In the early stages, pus formation (suppuration) is limited to the tubular lumina, but later abscesses rupture into the interstitial tissue. - Large masses of intratubular neutrophils frequently extend within involved nephrons into the collecting ducts, giving rise to characteristic white blood cell casts in the urine. - Typically, the glomeruli are not affected. - When obstruction is prominent, the pus does not drain and may fill the renal pelvis, calyces, and ureter, producing pyonephrosis.

UTI and diabetes

- The frequency of UTI is increased in diabetes because of the increased susceptibility to infection and neurogenic bladder dysfunction, which predispose to urine stasis. - vesicoureteral reflux (VUR) can be acquired in individuals with with bladder dysfunction secondary to diabetes. - predisposes to papillary necrosis

chronic pyelonephritis histo

- The microscopic changes are largely nonspecific, and similar alterations may be seen with other chronic tubulointerstitial disorders such as analgesic nephropathy. - Uneven interstitial fibrosis and an inflammatory infiltrate of lymphocytes, plasma cells, and occasionally neutrophils ~Dilation or contraction of tubules, with atrophy of the epithelial lining. > Many of the dilated tubules contain pink to blue, glassy-appearing PAS-positive casts, known as **colloid casts**, that suggest the appearance of thyroid tissue—hence the descriptive term thyroidization. - Often, neutrophils are seen within the tubules - Chronic inflammatory cell infiltration and fibrosis involving the calyceal mucosa and wall - Arteriolosclerosis may be caused by associated hypertension - Glomerulosclerosis that usually develops as a secondary process caused by nephron loss

causative organisms in acute pyelonephritis

- The principal causative organisms in acute pyelonephritis are enteric gram-negative bacilli. - Escherichia coli is by far the most common. ~Other important organisms are Proteus, Klebsiella, Enterobacter, and Pseudomonas > these usually are associated with recurrent infections, especially in individuals who undergo urinary tract manipulations or have congenital or acquired anomalies of the lower urinary tract. - Staphylococci and Streptococcus faecalis also may cause pyelonephritis, but they are uncommon pathogens in this setting. - Bacteria can reach the kidneys from the lower urinary tract (ascending infection) or through the bloodstream (hematogenous infection). - Ascending infection from the lower urinary tract is the most important and frequent route by which bacteria reach the kidney. - Adhesion of bacteria to mucosal surfaces is followed by colonization of the distal urethra (and the introitus in females). - The organisms then reach the bladder, by expansive growth of the colonies and by moving against the flow of urine. - This may occur during urethral instrumentation, including catheterization and cystoscopy. - In the absence of instrumentation, UTI most commonly affects females. - Because of the close proximity of the female urethra to the rectum, colonization by enteric bacteria can occur more readily in females. - Furthermore, the short urethra and trauma to the urethra during sexual intercourse facilitate the entry of bacteria into the urinary bladder. - Normally, bladder urine is sterile, because of the anti-microbial properties of the bladder mucosa and the flushing mechanism associated with periodic voiding of urine. - With outflow obstruction or bladder dysfunction, however, the natural defense mechanisms of the bladder are overwhelmed, setting the stage for UTI. - In the presence of stasis, bacteria introduced into the bladder can multiply undisturbed, without being flushed out or destroyed by the bladder wall. - Accordingly, UTI is particularly frequent among patients with urinary tract obstruction, as may occur with benign prostatic hyperplasia and uterine prolapse. - From the contaminated bladder urine, the bacteria ascend along the ureters to infect the renal pelvis and parenchyma. - Additional risk factors for UTI include preexisting renal conditions with renal scarring and intraparenchymal obstruction and also immunosuppressive therapy and immunodeficiency. - Although hematogenous spread is far less common than ascending infection, acute pyelonephritis may result from seeding of the kidneys by bacteria in the course of septicemia or infective endocarditis.

Organisms that cause UTIs

- Uropathogenic E. coli - Klebsiella spp - Proteus mirabilis - Enterobacter, Citrobacter, Morganella and Serratia spp - Staphylococcus saprophyticus - Staphylococcus aureus - Streptococcus agalactiae (Group B streptococci) - Leptospira interrogans

Malakoplakia

- an uncommon inflammatory disease that most commonly occurs in the bladder. - It results from defects in the phagocytic or degradative function of macrophages. - As a result of this defect, undigested bacterial products accumulate within distended phagosomes, which are seen in histologic sections as abundant granular material within the cytoplasm of macrophages. - The abnormal macrophages also contain laminated mineralized concretions known as **Michaelis-Gutmann bodies,** which result from deposition of calcium salts in the enlarged lysosomes.

Interstitial cystitis

- causes a chronic pelvic pain syndrome, typically in women. - It is characterized by suprapubic pain that increases with bladder filling and is relieved by bladder emptying, leading to very frequent urination during both day and night. - Other symptoms include urgency, hematuria, and dysuria. - Cystoscopic findings are nonspecific and include petechial hemorrhages. - Up to 50% of patients have spontaneous remissions. - Late in the course, transmural fibrosis may ensue, leading to a contracted bladder.

Balanitis and balanoposthitis

- refer to local inflammation of the glans penis and of the overlying prepuce, respectively. - Among the more common agents are Candida albicans, anaerobic bacteria, Gardnerella, and pyogenic bacteria. - Most cases occur as a consequence of poor hygiene in uncircumcised males, leading to the accumulation of desquamated epithelial cells, sweat, and debris, termed **smegma,** which acts as a local irritant. - Phimosis is a condition in which the prepuce cannot be retracted easily over the glans penis. - Phimosis may be a congenital anomaly, but most cases stem from scarring of the prepuce caused by balanoposthitis.

C. trachomatis

- small gram-negative bacterium that is an obligate intracellular pathogen. - It exists in two forms: (1) The infectious form, the elementary body, is capable of at least limited survival in the extracellular environment. > The elementary body is taken up by host cells, primarily through a process of receptor-mediated endocytosis. (2) Once inside the cell, the elementary body differentiates into a metabolically active form, termed the reticulate body. > Using the energy sources of the host cell, the reticulate body replicates and ultimately forms new infectious elementary bodies, which have a tropism for columnar epithelial cells. - C. trachomatis infections are associated with a wide range of clinical features that are virtually indistinguishable from those caused by N. gonorrhoeae. - Clinically, patients typically present 1 to 5 weeks after exposure with dysuria with or without urethral discharge. - Patients may develop epididymitis, prostatitis, pelvic inflammatory disease, pharyngitis, conjunctivitis, perihepatic inflammation, and, among individuals who engage in anal sex, proctitis. - It is the most common cause of epididymitis in young men. - Similar to gonococcus, a large percentage of both men and women are asymptomatic. - The infection may be transmitted to newborns during vaginal birth, where up to 15% of exposed newborns develop chlamydial pneumonia and 50% develop chlamydial conjunctivitis. - The morphologic and clinical features of chlamydial infection, with the exception of lymphogranuloma venereum, are virtually identical to those of gonorrhea. - The primary infection is characterized by a watery to mucopurulent discharge that contains a predominance of neutrophils. - Organisms are not visible in Gram-stained sections. - In contrast with the gonococcus, C. trachomatis cannot be isolated with the use of conventional culture media. - The diagnosis is best made by a nucleic acid amplification test on voided urine, which is now the gold standard. - Another important manifestation of chlamydial infection is reactive arthritis (formerly known as Reiter syndrome), predominantly in patients who are HLA-B27 positive. > This condition typically manifests as a combination of urethritis, conjunctivitis, arthritis, and generalized mucocutaneous lesions.

UTI and pregnancy

Increased incidence of UTI during pregnancy is attributed to urine stasis due to pressure on the bladder and ureters from the growing uterus.