Renal

Question 1

Urinary Tract Infections (Murray)

Answer 1

• Examination of urine specimens may be useful in diagnosing infections caused by Schistosoma haematobium and Trichomonas vaginalis
• Detection of eggs in urine can be accomplished using direct detection or concentration using the sedimentation centrifugation technique
• Eggs may be trapped in mucus or pus and frequently in last few drops of specimen rather than first portion
• Production of Schistosoma eggs fluctuates so exam multiple times over several days
• T. vaginalis may be found in urinary sediment of male and female patients

Question 2

Urinary Tract Infections (Robbins)

Answer 2

• Pyelonephritis is a renal disorder affecting the tubules, interstitium, and renal pelvis and is one of the most common diseases of the kidney
• Occurs in two forms: 1) Acute pyelonephritis is caused by bacterial infection and is the renal lesion associated with urinary tract infection. 2) Chronic pyelonephritis is a more complex disorder; bacterial infection plays a dominant role, but other factors (vesicoureteral reflux, obstruction) are involved in its pathogenesis.
• Bacterial infection of the lower urinary tract may be completely asymptomatic (asymptomatic bacteriuria) and most often remains localized to the bladder without the development of renal infection. However, lower urinary tract infection always carries the potential of spread to the kidney
• Dominant etiologic agents, accounting for more than 85% of cases of urinary tract infection, are Gram-negative bacilli that are normal inhabitants of the intestinal tract
• By far the most common is E. coli, followed by Proteus, Klebsiella, and Enterobacter. Streptococcus faecalis, also of enteric origin, staphylococci, and virtually every other bacterial and fungal agent can also cause lower urinary tract and renal infection
• In immunocompromised patients persons, particularly those with transplanted organs, viruses such as Polyomavirus, cytomegalovirus, and adenovirus can also be a cause of renal infection
• In most patients with urinary tract infection, the infecting organisms are derived from the patient’s own fecal flora (endogenous infection)
• There are two routes by which bacteria reaches the kidneys: 1) through the bloodstream (hematogenous infection; less common and results from seeding of the kidneys by bacteria from distant foci in the course of septicemia or infective endocarditis) 2) from lower urinary tract (ascending infection)
• Hematogenous infection is more common in presence of ureteral obstruction, in debilitated patients, in patients receiving immunosuppressive therapy, and with nonenteric organisms, such as staphylococci and certain fungi and viruses
• Ascending infection is the most common cause of clinical pyelonephritis

Question 3

Steps of Ascending Infection (Robbins)

Answer 3

1) Colonization of the distal urethra and introitus (in the female) by coliform bacteria
- This colonization is influenced by the ability of bacteria to adhere to urethral mucosal epithelial cells
- Adherence involves adhesins (specifically pyelonephritis-associated pili [pap] gene) on the P-fimbriae (pili) of bacteria that interact with receptors on the surface of uroepithelial cells.
2) From urethra to the bladder, organisms gain enterance during urethral catheterization or other instrumentation
- Long-term catheterization carries a risk of infection
- In absence of catheterization, urinary infections are much more common in females, and this has been ascribed to the shorter urethra in females, as well as the absence of antibacterial properties such as are found in prostatic fluid, hormonal changes affecting adherence of bacteria to the mucosa, and urethral trauma during sexual intercourse, or a combination of these factors
3) Urinary tract obstruction and stasis of urine
- Ordinarily organisms introduced into the bladder are cleared by the continual flushing of voiding and by antibacterial mechanisms, however, outflow obstruction or bladder dysfunction results in incomplete emptying and increased residual volume of urine
- Stasis allows introduced bacteria to multiply unhindered -> patients with lower urinary tract obstruction, such as may occur with benign prostatic hypertrophy, tumors, or calculi, or with neurogenic bladder dysfunction caused by diabetes or spinal cord injury
4) Vesicoureteral reflux
- Although obstruction is an important predisposing factor in ascending infection, it is incompetence of the vesicoureteral valve that allows bacteria to ascend the ureter into the renal pelvis
- The normal ureteral insertion into the bladder is a competent one-way valve that prevents retrograde flow of urine, especially during micturition, when the intravesical pressure rises
- Reflux most often due to a congenital absence or shortening of the intravesical portion of the ureter, such that the ureter is not compressed during micturition
- Bacterial of inflammatory products on ureteral contractility, can cause or accentuate vesicoureteral reflux, particularly in children
5) Intrarenal reflux
- Vesicoureteral reflux also affords a ready mechanism by which the infected bladder urine can be propelled up to the renal pelvis and deep into the renal parenchyma through open ducts at the tips of the papillae (intrarenal reflux)
- Intrarenal reflux is most common in the upper and lower poles of the kidney, where papillae tend to have flattened or concave tips rather than the convex pointed type present in the midzones of the kidney
- In the absence of vesicoureteral reflux, infection usually remains localized in the bladder. Thus, the majority of individuals with repeated or persistent bacterial colonization of the urinary tract suffer from cystitis and urethritis (lower urinary tract infection) rather than pyelonephritis

Question 4

Acute Pyelonephritis (Robbins)

Answer 4

• Acute pyelonephritis is an acute suppurative inflammation of the kidney caused by bacterial and sometimes viral (e.g. polyomavirus) infection, whether hematogenous and induced by septicemic spread or ascending and associated with vesicoureteral reflux
• Hallmarks of acute pyelonephritis are patchy interstitial suppurative inflammation, intratubular aggregates of neutrophils, and tubular necrosis
• Suppuration may occur as discrete focal abscesses involving one or both kidneys, which can extend to large wedge-shaped areas of suppuration
• Three complications of acute pyelonephritis are encountered in special circumstances:
  1) Papillary necrosis is seen mainly in diabetics and in those with urinary tract obstruction. Mainly bilateral but can be unilateral. On microscopic examination, the necrotic tissue shows characteristic coagulative necrosis, with preservation of outlines of tubules
  2) Pyelonephritis is seen when there is total or almost complete obstruction, particularly when it is high in the urinary tract. The suppurative exudate is unable to drain and thus fills the renal pelvis, calyces, and ureter with pus
  3) Perinephric abscess is an extension of suppurative inflammation through the renal capsule into the perinephric tissue
• After the acute phase of pyelonephritis, healing occurs. The inflammatory foci are eventually replaced by irregular scars that can be seen on the cortical surface as fibrous depressions
• The pyelonephritic scar is almost always associated with inflammation, fibrosis, and deformation of the underlying calyx and pelvis, reflecting the role of ascending infection and vesicoureteral reflux in the pathogenesis of the disease
• Acute pyelonephritis associated with predisposing conditions:
• Urinary tract obstruction
• Instrumentation (catheterization)
• Vesicoureteral reflux
• Pregnancy
• Gender and age (1 - 40 y.o. females more common. With increasing age the incidence in males rises as a result of prostatic hypertrophy and instrumentation)
• Preexisting renal lesions
• Diabetes mellitus
• Immunosuppression and immunodeficiency
• An emerging viral pathogen causing pyelonephritis in kidney allografts is polyomavirus
• Latent infection with polyomavirus is widespread in the general population, but immunosuppressive of the allograft recipient can lead to reactivation of latent infection and the development of a nephropathy resulting in allograft failure
• This form of polyomavirus nephropathy, now referred to as polyomavirus nephropathy, is characterized by viral infection to tubular epithelial cell nuclei

Question 5

Klebsiella

Answer 5

• Enterobacteriaceae (Gram-negative rod)
• Prominent capsule that is responsible for the mucoid appearance of isolated colonies and the enhanced virulence of the organisms in vivo
• Klebsiella granulomatis is the etiologic agent of granuloma inguinale, a granulomatous disease affecting the genitalia and inguinal area (chronic genital ulcerative disease)
• Granuloma inguinale is a rare disease in the U.S. but endemic in parts of Papua New Guinea, the Caribbean, South America, India, southern Africa, Vietnam, and Australia
• It can be transmitted after repeated exposure through sexual intercourse or nonsexual trauma to the genitalia
• After prolonged incubation of weeks to months, subcutaneous nodules appear on the genitalia or in the inguinal area
• These nodules subsequently break down, revealing one or more painless granulomatous lesions that can extend and coalesce
• Klebsiella rhinoscleromatis causes a granulomatous disease of the nose
• Klebsiella ozaenae causes chronic atrophic rhinitis
• Most commonly isolated members of this genus are Klebsiella pneumoniae and Klebsiella oxytoca, which can cause community or hospital acquired primary lobar pneumonia
• Klebsiella pneumoniae can also cause UTI’s
• Pneumonia frequently involves the necrotic destruction of alveolar spaces, formation of cavities, and the production of blood-tinged sputum
• Also cause wound, soft tissue, and urinary tract infections

Question 6

Proteus

Answer 6

• Enterobacteriaceae (Gram-negative rod)
• Infections of the urinary tract with Proteus mirabilis are the most common diseases produced by this genus
• Produces large quantities of urease, which splits urea into carbon dioxide and ammonia (process raises urine pH, precipitating magnesium and calcium in the form of struvite and apatite crystals, respectively, and results in renal (kidney) stones
• Increased alkalinity is also toxic to the uroepithelium
• Produces as many as six different types of fimbriae, some of which are important for adherence to uroepithelium
• Produce infections only when the bacteria leave the intestinal tract
• P vulgaris and Morganella morganii are important nosocomial pathogens
• The rapid motility of Proteus may contribute to its invasion of the urinary tract
• Strains of Proteus vary greatly in antibiotic sensitivity (P mirabilis is often inhibited by penicillins; the most active antibiotics for other members of the group are aminoglycosides and cephalosporins

Question 7

Enterobacter, Citrobacer, Morganella, Serratia

Answer 7

• Primary infections caused by Enterobacter, Citrobacter, Morganella, and Serratia are rare in immunocompetent patients
• More commonly causes of hospital-acquired infections in neonates and immunocompromised patients
• Citrobacter koseri has been recognized to have a predilection for causing meningitis and brain abscesses in neonates***
• Antibiotics can be ineffective as the organisms are frequently resistant to multiple antibiotics
• Resistance is particularly serious for enterobacter species

Question 8

Enterobacter

Answer 8

• Three species of Enterobacter cause the majority of infection:
  1) E cloacae
  2) E aerogenes
  3) E sakazakii
• These ferment lactose, may contain capsules that produce mucoid colonies, and they are motile
• Cause a broad range of hospital acquired infections such as pneumonia, UTI’s, wound, and device infections
• Most strains possess a chromosomal B-lactamase called ampC which renders them intrinsically resistant to ampicillin and first and second generation cephalosporins
• Mutants may hyperproduce B-lactamase conferring resistance to third generation cephalosporins

Question 9

Serratia

Answer 9

• S marcescens is a common opportunistic pathogen in hospitalized patients
• Serratia (usually nonpigmented) causes pneumonia, bacteremia, and endocarditis - especially in narcotics addicts and hospitalized patients
• Only about 10% of isolates form the red pigment (prodigiosin) that characterizes Serratia marcescens
• Often multiply resistant to aminoglycosides and penicillins; infections can be treated with third generation cephalosporins

Question 10

Leptospira

Answer 10

• Thin, coiled spirochetes with a hook at one or both pointed ends
• Motility is by means of two periplasmic flagella extending the length of the bacteria and anchored at opposite ends
• Obligate aerobes with optimum growth at 28 - 30*C in media supplemented with B2, B12, long-chain fatty acids, and ammonium salts
• Can cause a mild influenza-like febrile illness, or sever systemic disease (Weil syndrome), with renal and hepatic failure, extensive vasculitis, myocarditis, and death
• Because thin and highly motile, the can penetrate intact mucous membranes or skin through small cuts or abrasions
• Then spread in blood to all tissues, including the CNS
• L. interrogans multiply rapidly and damage the endothelium of small blood vessels, resulting in the major clinical manifestations of disease (meningitis, hepatic and renal dysfunction, hemorrhage)
• Can be found in blood and CSF early in the disease and in urine during the later stages
• Clearance of leptospires occurs when humoral immunity develops, however some clinical manifestations may stem from immunologic reactions with the organisms (ex: meningitis develops after the organisms have been removed from the CSF and immune complexes have been detected in renal lesions
• Worldwide distribution (100-200 human infections occur in US; half of cases reported in Hawaii***)
• Underdiagnosed as most infections are mild and misdiagnosed as a “viral syndrome” or viral aseptic meningitis
• Leptospires infect two types of hosts: reservoir hosts and incidental hosts
• Endemic, chronic infections are established in reservoir hosts, which serve as a permanent reservoir for maintaining the bacteria
• The MOST COMMON RESERVOIRS are RODENTS and other SMALL MAMMALS
• In these reservoirs, the leptospires colonize the renal tubules and are shed in large quantities via the URINE
• Streams, rivers, standing water, and moist soil can be contaminated with urine from infected animals, with organisms surviving for as long as 6 weeks
• Contaminated water or direct exposure to infected animals can serve as a source for infetion in incidental hosts (dogs, farm animals, humans)
• Most human infections result from recreational exposure to contaminated water (lakes) or occupational exposure to infected animals (Farmers, slaughterhouse workers, vets)
• Occur during warm months, when recreational exposure is greatest
• Infection is demonstrated via specific antibodies
• Infection is introduced through skin abrasions or conjunctiva
• Initial phase is similar to influenza-like illness with fever and myalgia (muscle pain) (leptospires can be isolated in the CSF at this point as the patient is bacteremic)
• This can resolve or patient can progress to a second stage with sudden onset of headaches, myalgia, chills, abdominal pain, and conjuctival suffusion (reddening of the eye)
• Can progress to vascular collapse, thrombocytopenia, hemorrhage, and hepatic and renal dysfunction
• Cannot be seen by light microscope
• Microscopic agglutination test (MAT) is the serological test to diagnose
• Treat with IV penicillin or doxycycline (doxycycline can also be used to prevent the disease in those who have been exposed to contaminated water or infected animals)

Question 11

Schistosomes

Answer 11

• Schistosomiasis is a major parasitic infection of tropical areas, with some 200 million infections worldwide
• Three main ones associated with human disease:
  1) S mansoni
  2) S japonicum
  3) S haematobium
• Collectively produce a disease know as schistosomiasis, also known as bilharziasis or snail fever
• Male or female rather than hermaphroditic (unlike other flukes***), and their eggs do not have an operculum
• Obligate intravascular parasites and are not found in cavities, ducts, and other tissues
• Infective forms are skin-penetrating cercariae liberated form snails, and these differ from other flukes in that they are not eaten on vegetation, in fish, or in crustaceans
• Infection is initiated by free-swimming cercaria in fresh water that penetrate intact skin, enter circulation, and develop in the intrahepatic portal circulation (S. mansoni and S. japonicum) or in the vesical, prostatic, rectal, and uterine plexuses and veins (S. haematobium)
• Female has a long, slender, cylindrical body, whereas the shorter male, which appears cyclindrical, is actually flat (female sits in male’s gynecophoral canal for reproduction)
• As the worms develop in the portal circulation, they elaborate a remarkable defense against host resistance (coat themselves in host antigens so the host doesn’t recognize them as foreign)
• This can lead to chronic infections that last 20-30 years or longer
• After they develop in the portal vein, the male and female pair up and migrate to their final locations (S. japonicum and S. mansoni are found in the mesenteric veins and produce intestinal schistosomiasis; S. haematobium occurs in veins around the urinary bladder and cause vesicular schistosomiasis)
• Produce 300-3000 eggs daily for 4-35 years
• These eggs elicit an intense inflammatory response that can lead to microabscesses
• Larvae inside the eggs produce enzymes that aid in tissue destruction and allow the eggs to pass through the mucosa and into the lumen of the bowel and bladder, where they are passed to the external environment in the feces and urine
• The eggs hatch quickly on reaching fresh water to release motile miracidia that go on to invade their snail hosts to develop into infectious circariae to infect more humans/mammals
• Main disease comes from the host response to the eggs***
• The onset of oviposition results in a symptom complex known as Katayama syndrome, which is marked by fever, chills, cough, urticaria, arthralgias, lymphadenopathy, splenomegaly, and abdominal pain (result of release of parasite antigens with subsequent immune complex formation)

Question 12

Schistosoma mansoni

Answer 12

• S. mansoni usually resides in the small branches of the inferior mesenteric vein near the lower colon
• The species of Schistosoma can be differentiated by their characteristic egg morphology
• S. mansoni’s eggs are oval and possess a sharp lateral spine
• Most widespread of the three and is endemic in Africa, Saudi Arabia, and Madagascar (also well established in the Western Hemisphere, particularly in Brazil, Suriname, Venezuela, West Indies, and Puerto Rico
• In all of these areas, there are also reservoir hosts such as primates, marsupials, and rodents
• Considered a disease of economic progress; the development of massive land irrigation projects in desert and tropical areas has resulted in the dispersion of infected humans and snails to previously uninvolved areas
• Cercarial penetration of intact skin may be seen as dermatitis with allergic reactions, pruritus, and edema
• Migrating worms in the lungs may produce cough; as they reach the liver, hepatitis may appear
• Fever, malaise, abdominal pain, and tenderness of the liver
• Deposition of eggs in the bowel wall with associated abdominal pain, diarrhea, and blood in the stool
• Eggs may be carried by portal vein to the liver, where inflammation can lead to periportal fibrosis and eventually to portal HTN and its associated manifestations
• Chronic infections w/ S. mansoni produces a dramatic hepatosplenomegaly with large accumulations of ascitic fluid in the peritoneal cavity
• On gross examination, the liver is studded with white granulomas (pseudotubercles)
• Severe neurological problems may follow when eggs are deposited in the spinal cord and brain
• In fatal schistosomiasis caused by S. mansoni, fibrous tissue, reacting to the eggs in the liver, surrounds the portal vein in a thick, grossly visible layer (“CLAY PIPESTEM FIBROSIS”)
• Diagnosis of schistosomiasis is established by demonstration of characteristic eggs in FECES (large golden eggs with sharp lateral spine)
• Using rectal biopsy, clinician can see the egg tracks laid by the worms in rectal vessels
• Treat with PRAZIQUANTEL (alternative = oxamniquine)
• Schistosomal dermatitis and Katayama syndrome may be treated with antihistamines and corticosteroids
• Improved sanitation and control of human fecal deposits are critical

Question 13

Schistosoma japonicum

Answer 13

• S. japonicum resides in branches of superior mesenteric vein around the small intestine and in the inferior mesenteric vessels
• Eggs are smaller, almost spherical, and possess a tiny spine
• Produced in greater number than the other species and because of their size, carried to more sites in the body (liver, lungs, brain)
• Infection with a few S. japonicum adults can be more severe than the others
• The oriental blood fluke is found only in China, Japan, the Philippines, and on the island of Sulawesi, Indonesia (Think people working in rice paddies and on irrigation projects where the infective snail is present)
• Broad range of reservoir hosts, many of which are domestic (dogs, cats, cattle, horses, and pigs)
• Initial stages of infection are similar with dermatitis, allergic reactions, fever, and malaise, followed by abdominal discomfort and diarrhea
  Katayama syndrome associated with the onset of oviposition is observed more commonly with S. japonicum than with S. mansoni
• In chronic infection, hepatosplenic disease, portal hypertension, bleeding esophageal varices, and accumulation of ascitic fluid are commonly seen
• Granulomas that appear as pseudotubercles in and on the liver are common, along with the clay pipestem fibrosis as described for S. mansoni
• S. japonicum frequently involves cerebral structures when eggs reach the brain and granulomas develop around them
• Neurologic manifestations include lethargy, speech impairment, visual defects, and seizures
• STOOL examination demonstrates the small, golden eggs with tiny spines
• Treat with PRAZIQUANTEL

Question 14

Schistosoma haematobium

Answer 14

• 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 the urine
• Occurs throughout the Nile Valley and in many other parts of Africa, including islands off the eastern coast (also 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, S. haematobium produces hematuria, dysuria, and urinary frequency as early symptoms
• 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 the development of obstructive uropathy
• Infections involving many flukes frequently demonstrate SQUAMOUS CELL CARCINOMA of the bladder (most common cause of bladder cancer in Egypt and other parts of Africa)
• The granulomas and pseudotubercles seen in the bladder may also be present in the lungs
• Examination of URINE specimens reveals the large, terminally spined eggs (may appear in stool if worms have migrated to mesenteric vessels)
• Treat with PRAZIQUANTEL