BMS250 - Wk 7

Microbiology of the Genitourinary System and Physiology of Lower Urinary Tract

• Course covers gross anatomy of the urinary system, including kidneys, ureters, bladder, urethral sphincters, prostate, and associated nerves.
• It integrates the impact of the somatic, sympathetic, and parasympathetic nervous systems on micturition (bladder control).
• Course describes the role of umbrella cells in the bladder, vesicoureteric reflux, and urinary tract infection pathogenesis.
• It will relate the role of vaginal microbiota and its relation to the risk of urinary tract infections.
• It will describe the biology, virulence factors, pathogenesis, and clinical manifestations relative to UTIs for E. coli, Proteus mirabilis, Klebsiella sp., P. aeruginosa, Staphylococcus saprophyticus, and Enterococcus spp.
• Course includes interstitial cystitis, bladder cancer, their pathogenesis, clinical features, diagnostic findings, and complications.

The Kidneys

• The kidneys produce urine, conveyed by the ureters to the urinary bladder in the pelvis.
• The superomedial part of each kidney sits near a suprarenal gland.
• A weak fascial septum separates the glands from the kidneys, not actually attaching.
• Suprarenal glands function as part of the endocrine system, separate from kidney function.
• Kidneys, ureters, vessels, and suprarenal glands are primary retroperitoneal structures on the posterior abdominal wall.
• Perinephric fat surrounds the kidneys/vessels, extends into the renal sinus (hollow center).
• The renal hilum is the entrance to the renal sinus inside the kidney.
• Structures (vessels, nerves, and urine drainage) enter/exit the renal sinus through the renal hilum.
• The left kidney hilum is near the transpyloric plane, about 5 cm from the median plane.
• The transpyloric plane passes through the superior right kidney pole, which is roughly 5.5 cm lower than the left probably due to the liver.

Renal Arteries & Veins

• The renal arteries arise at the level of the IV disc between L1 and L2 vertebrae.
• The right renal artery (longer) passes posterior to the inferior vena cava (IVC).
• The artery usually divides close to the hilum into five segmental arteries that are end arteries, areas supplied are independent/surgically resectable.
• The superior (apical) segment is supplied by a superior (apical) segmental artery.
• Anterosuperior/anteroinferior segments are supplied by their respective segmental arteries.
• The inferior segment is supplied by the inferior segmental artery.
• All these arteries mentioned originate from the anterior branch of the renal artery.
• The posterior segmental artery originates from a continuation of the posterior branch of the renal artery, supplies the posterior segment of kidney.
• Several renal veins drain each kidney and unite in a variable fashion to form the right and left renal veins
• these veins lie anterior to the right and left renal arteries.
• The right renal vein receives blood from the right kidney
• The longer left renal vein receives, in addition to the left kidney, the left suprarenal vein, the left gonadal
• Each renal vein drains into the IVC

Autonomic Nerves (Kidney and Ureters)

• Nerves to kidneys come from the renal nerve plexus consisting sympathetic/parasympathetic fibers.
• Renal nerve plexus gets fibers from the abdominopelvic splanchnic nerves.
• Nerves for the abdominal ureter part are from the abdominal aortic, renal, and superior hypogastric plexuses.
• Visceral afferent fibers conveying pain sensation (obstruction, distension) follow sympathetic fibers retrograde to spinal ganglia T11-L2.
• Ureteric pain refers to the ipsilateral lower quadrant of abdominal wall (especially groin).

Bladder Nerves

• Sympathetic fibers go from the inferior thoracic and upper lumbar spinal cord through the hypogastric plexuses.
• Parasympathetic fibers go sacral spinal cord levels through the pelvic splanchnic nerves and the inferior hypogastric plexus.
• The parasympathetic fibers are motor to the detrusor muscle (bladder wall) and inhibitory to the internal urethral sphincter of the male bladder.
• Visceral afferent fibers stimulate stretching, bladder contracts reflexively, internal urethral sphincter relaxes (males), and urine flows into urethra.
• A sympathetic response, such as self-consciousness when standing at the urinal in front of a waiting line can cause the internal sphincter to contract, hampering the ability to urinate until parasympathetic inhibition of the sphincter occurs.
• Sensory fibers from most of the bladder are visceral.
• The afferent reflex follows the parasympathetic fibers, as do pain sensations from the inferior part of the bladder.
• Superior bladder is covered with peritoneum, therefore superior to the pelvic pain line.
• Pain fibers from superior bladder follow sympathetic fibers retrogradely to inferior thoracic and upper lumbar spinal ganglia (T11-L2 or L3).
• Internal and external urethral sphincters (both males and females) prevent urine release.
• The internal urethral sphincter controls involuntary urine flow from bladder to urethra.
• The external urethral sphincter controls voluntary urine flow from the bladder to urethra.
• Damage can cause urinary incontinence.
• Males only: the internal urethral sphincter also prevents semen flow into the male bladder during ejaculation.

Male Urethra

• Nerves derive from the prostatic plexus containing sympathetic, parasympathetic, and visceral afferent fibers.
• Prostatic plexus: one of the pelvic plexuses, inferior extension of the vesical plexus) arising as organ-specific extensions of the inferior hypogastric plexus

Prostate

• Prostate is richly innervated by sympathetic nerve fibers.
• Presynaptic sympathetic fibers from the T12-L2 (or L3) spinal cord column.
• They traverse vertebral ganglia to become lumbar (abdominopelvic) splanchnic nerves and the hypogastric and pelvic plexuses.
• Presynaptic parasympathetic fibers from S2 and S3 spinal cord segments traverse pelvic splanchnic nerves to inferior hypogastric/pelvic plexuses.
• Parasympathetic fibers traversing the prostatic nerve plexus form the cavernous nerves.

Female Urethra

• The female urethra (approximately 4 cm long and 6 mm in diameter) goes from the internal urethral orifice anteroinferiorly posterior pubic symphysis to external urethral orifice.
• Musculature surrounding internal urethral orifice is not organized into an internal sphincter.
• The female external urethral orifice is in the vestibule of the vagina anterior to the vaginal.
• The urethra is anterior to the vagina.
• The urethra and vagina pass through the pelvic diaphragm, external urethral sphincter, and perineal membrane.
• Nerves to urethra derive from the vesical n. plexus and the pudendal n.
• Visceral afferents from most of the urethra travel in the pelvic splanchnic nerves, somatic afferents from the pudendal n.
• Both visceral and somatic afferent fibers extend from cell bodies in the S2-S4 spinal ganglia

Micturition

• Micturition and lower urinary tract (LUT) function: interplay of autonomic and somatic circuitry.
• Goal: maintain a low-pressure bladder during filling, periodically empty voluntarily.
• Normal neural circuitry allows voluntary switching between storage/voiding phases on perceived sense of bladder fullness, social appropriateness.
• During normal bladder filling, the sympathetic (hypogastric n.) and somatic (pudendal n.) mediate contraction of the internal smooth and external striated urethral sphincters.
• As bladder fills, sympathetic-mediated detrusor inhibition allows the bladder to accommodate increased volume at low intravesical pressures.
• Primary detrusor muscle function: contract to push urine from bladder into urethra and relax to store urine in unitary bladder.
• Deciding to urinate: the pontine micturition center (PMC) is released from inhibitory control of the higher cortical and subcortical brain centres, initiating the voiding process.
• The parasympathetic system activates stimulating a detrusor contraction the relaxation of the pelvic floor and and external and internal urethral sphincter.
• fMRI studies clarified central nervous system (CNS) control, periaqueductal gray (PAG) pivotal in the switching of circuitry between storage and voiding.
• Frontal, midcingulate, and subcortical areas control the PAG/LUT, any damage can cause LUT dysfunction.

Umbrella Cells

• Superficial specialized epithelial cells found in the urinary tract lining.
• They help maintain integrity/impermeability of the bladder wall.
• They are resistant to urine.
• Characterized by large size, flattened shape, extensive apical membane folds ("plaques" or "ridges").
• These increase surface area, allowing expansion/contraction for filling/emptying.
• Apical membane adaptations: Numerous densely packed, rigid uroplakin plaques that contribute to impermeability.
• Tight junctions: Umbrella cells have tight junctions with neighboring cells, for regulating movement of ions, water and solutes maintaining the integrity of the bladder
• Surface area enlargement, the apical surface of umbrella cells can expand and contract significantly to accommodate changes in bladder.
• Resistance to mechanical stress: presence of cytokeratin filaments and actin bundles for robust support.
• Specialized transport mechanisms, ex: aquaporin water channels to rapidly reabsorb water concentrate/conserve during dehydration.
• Uroplakin synthesis and turnover: constant synthesis and turnover which helps maintain the integrity and functionality of the apical membrane, ensuring effective barrier function prevents penetration of pathogens

Umbrella Cells

• Overall, the physiological role of umbrella cells is to
  • Maintain bladder integrity
  • Prevent leakage of urine
  • Provide protection to underlying tissues from substances in urine.

Vesicoureteric

• "Vesicoureteric:" junction between urinary bladder and ureter where the ureter enters.
• Also called ureterovesical junction (UVJ).
• Prevents backflow of urine from bladder into ureter (vesicoureteral reflux or VUR).
• The vesicoureteric junction has ureteral musculature that contracts during filling (prevents urine reflux) and the intravesical ureteral tunnel a valve for ensuring one-way urine flow into bladder.

Vesicoureteric Reflux

• Vesicoureteral reflux (VUR): urine flows backward from the bladder into one or both ureters and possibly kidneys.
• The valve-like mechanism where the ureter meets the bladder prevents urine from backing up, individuals with VUR has defected valves, allowing.
• Classified into different grades: grade I (mildest) to grade V (most severe) urine all the way up to the kidneys.
• More common in infants/young children; associated recurrent urinary tract infections (UTIs), urinary incontinence, and kidney damage (untreated).
• Treatment: antibiotic prophylaxis (prevent UTIs), surgical correction of vesicoureteric junction, or endoscopic injection of bulking agent to improve valve function.

Urinary Tract Infections

• May be asymptomatic (subclinical infection) or symptomatic (disease)
• Includes asymptomatic bacteriuria (ASB), cystitis, prostatitis, and pyelonephritis.
• UTI/ASB suggest bacteria in urinary tract accompanied by WBCs/inflammatory cytokines.
• ASB occurs without attributable symptoms ASB may not need treatment
• UTI typically implies symptomatic disease, warrants antimicrobial therapy

UTI Pathogenesis

• Urinary tract is a continuous anatomical unit from urethra to the kidneys.
• Most UTIs establish an Infection from the bladder.
• Continued ascent up the ureter to the kidney is the pathway for renal infections.
• Not all bacteria in the bladder leads to sustained infection.
• Bacteria often enter the bladder after sex eliminated by normal voiding innate host defence.
• Foreign bodies act as an inert surface for bacterial colonization. Promoting infection
• Simplest Form: anything that increases the likelihood of bacteria is there an.

Asymptomatic Bacteriuria

• Detected incidentally during screening urine culture for unrelated reasons.
• Systemic signs (fever/altered mental status) are nonspecific.
• ASB is considered only when there is no local or systemic symptoms of the urinary tract.

Cystitis

• Typical symptoms of the uncomplicated cystitis are
  • Dysuria
  • Urinary frequency
  • Urgency
  • Nocturia, hesitancy, suprapubic discomfort, and gross hematuria too
• Complicated Cystitis
  • Unilateral back or flank pain suggest that the upper urinary tract is involved
  • Fever suggest invasive infection beyond the bladder, involving kidney, prostate, or bloodstream.

Pyelonephritis

• Mild pyelonephritis
  • Can present: low-grade fever, lower-back/costovertebral-angle pain.
• Severe pyelonephritis
  • May manifest: high fever, rigors, nausea, vomiting, and flank pain.
• Symptoms are generally acute, cystitis symptoms may be absent.
• Fever distinguishes from cystitis.
• Fever exhibits a high spiking "picket-fence” pattern, resolves over 72 h.
• Bacteremia develops in 20-30% of cases.
• Patient with diabetes may present obstructive uropathy/acute papillary necrosis (sloughed papillae obstruct the ureter).
• Papillary necrosis in some cases of pyelonephritis, Obstruction, sickle cell disanalgesic nephropathy, or combination.
• Rare cases bilateral papillary necrosis, rapid: rises in serum creatinine level first.
• Emphysematous pyelonephritis is a severe form that associates Production of gas in renal + perinephric tissues. Occurs mostly in diabetic patients.
• Xanthogranulomatous pyelonephritis: chronic obstruction (often staghorn calculi), chronic infection, suppurative destruction of renal tissue.
• Pathologic examination: residual tissue often has yellow coloration and infiltration by lipid-laden macrophages. Can be complicated by intraparenchymal abscess suspect when fever and bacteria.

Urosepsis

• Starts in the urinary tract - usually kidneys or bladder
• Causes a response in the bloodstream - known as sepsis.
• Widespread inflammation can cause rapid breathing . rapid heat rate can also confuse body and decreased urine.
• The prompt treatment using IV antibiotics is very critical. If this becomes untreated the results may vary.

Normal Vaginal Microbiota

• A diverse community of microorganisms in the vagina maintaining its health/function.
• Predominant microorganisms: Lactobacillus species which includes:
• L. crispatus, L. gasseri, L. jensenii, and L. iners
• Creates creating the environment in order acid low pH In the vagina which results in inhibiting the growth of multiple bacteria and maintaining helath.
• Can differ depending on hormonal changes, activities ,antibiotic abuse.
• For a healthy vagiina - The stable acidic ph levels helps maintain against infection from bacteria.

UTI Risk Factors

• Mechanical factors increase bacterial growth; Obstruction,short urethra
• catheterzation bypasses the urethras
• Colonization of vaginal areas increase risk in women from 1 -+ compared to men less then .1

Urinary Tract

• E coli - 75% outpatient. - common impatient.
• Klebsiella - 15% outpatient - common impatient.
• Proteus - 5% outpatient - common impatient.
• Enterococci 2% outpatient - common impatient.
• Staphylococcus - outpatient /group B strep - - common impatient.
• Pseudomonas - Rare outpatient - common impatient.
• KEY POINTS
  • E. coli is the most frequent pathogen, followed by Klebsiella and Proteus.
  • S. saprophyticus causes 5 -15% of cystitis cases in young, sexually active women.
• Nosocomial infections usually involve Enterobacter, Pseudomonas, enterococci, Candida, S. epidermidis, and Corynebacterium.

E. Coli

• An anatomically normal urinary tract presents a stronger barrier to infection thus strains are known to cause infections via strains.
  • including surface adhesins that mediate binding to specific receptors on the surface of uroepithelial cells.
• hair like protein structures that interact receptors.
  • surface adhesins are the P fimbriae
• P denotes binding to blood group antigen p
• key part of helping lead to pyelonepthris.
• pili with mannose is part in assisting with the bladder epithelium .
• cells increase resistance hemolysin increases cells in a invasive way.

Proteus

• Bacterial synthesis - The bacteria is made to grow but needs guanine arginine and glutamine
  • Pathogen has play an key tool in the role of development
• Urease - production of generated ammonia
• Proteus generates ammonium and brings high alkaline which is more related to increases likelihood in increase store growth.

Klebsiella

• Particularly in healthcare settings:
• Adherence and colonization:
  • Once in the urinary tract, Klebsiella bacteria adhere to and colonize the mucosal surfaces of the bladder or kidney tissues. Adherence is facilitated by various surface structures, including fimbriae and adhesins, which allow the bacteria to attach to host cells.
• Invasion and evasion of host defences
• Possess mechanisms to invade host cells and evade the immune system They may invade bladder epithelial cells, allowing them to evade immune detection and persist within the urinary trac
• an form biofilms on the surface of urinary catheters or within the urinary tract. Biofilms provide protection against antibiotics and host immune responses, making the eradication of the infection more challenging. Virulence factors -Produce various virulence factors that contribute to their pathogenicity, including capsule polysaccharides, lipopolysaccharides (LPS), siderophores, and toxins. These factors help the bacteria to evade host defences, adhere to surfaces, acquire nutrients, and cause tissue damage. Antibiotic resistance
• Notorious for their ability to develop antibiotic resistance, including resistance to multiple antibiotics through the acquisition of resistance genes This makes treatment of Klebsiella UTIs more challenging and may require the use o. alternative antibiotics or combination therapy.

Encterococci

• Usually associated with catheterization and abnormalities of the anatomy.

Interstitial

• A chronic condition in the bladder with pain in the pelvis.
• Autoimmunity is a component
• Infection to help in the urinary
• Dysfuntion and lack of pain is attributed in urinary pain.
  • Researches show with identification causes observation of micro between certain people with IC and other.
  • Researchers also note that dysbiosis disturbance to the low urinary tract in a system.

Autoimmunity (Interstitial Cystitis)

• Observation has shown that autoimmune disorder comes with ic patients.
  • Antibodies within the bladder mucosa have been found.
    • Lymphocytes , edema . Detrusor.
    • However researchers been unable to make this better.

Hunner Lesions

• A subset of Patients which show bladder inflammations
  • Has well characterized Inflamed analysis with history
  • Identified wether under cyostocopy and visual cell counts.
  • Also inflammation is subtle

Interstitial Cystitis Dysfuction

• The stratified cells of the wall are what the cells are known for and provides robust Function, is fulfilled the most for the interluminal.
• defects: GAG may be attributed to barrier function which may not help.

Interstitial Cystitis

• Both female and male , can attribute to bladder.
  • Frequency is one of the main functions.

Diagnostics/Complications of Interstitial Cystitis

• Often difficult to diagnose
  • tools like lab testing physical exams make diagnoses IC.
• Complications. can come with significant health and disability.
  • Economically very similar with many different mental disabilities.
• -Subacte leads to continual increase within the five week of the final stage.
  • Sympots have waves , which leads to not many symptoms getting much.
  • However improvement does exist.

Bladder Cancer - The Important Aspects

• the most site of cancer -older is most common. (65 yr)
• men more common
• (90%) cell cancers are uncommon -multi factors contribute into the cancers -reoccurnes is common -10- % for grade tumors -Tumours are present in decrease with the five year survival.

Bladder Cancer

• Smoking may increase risk due dye
• 2% and 7 percent is the total affect
• The most important risk is smoking is often infection. -Drug abuse.
• radiation

Tumours (Bladder Cancer)

• Over all main issue from is epithelial
• Neophlastic arising. -Benigna. At the other end may be maligant. Smaller less commojn

Tumour and cells

• Cells have shown the the incident in men.
• small 2-5 mms.
• rare typical present in modules
• In the general area
• can be removed

Primary and secondary Tummours

• Term is reserved when the the bladder is inside
• involved epitheliu,. Iatria

Characteristics

• One third of the cardinomes are often associated
• more invasive
• The inside often has the appear of that are near that
• At can extend can extend to multiple parts Tumora that involve to the the urethra can be transferred

Tumours of the B ladder

• Ureotheral : Low grade

Tummours: Pt 2

• Hgh -show hyper. Dis organized. IN vasive cells, nodes can attribute to cells that cause the invasion
• In the flat or cartosonas will continue this.

Tumour Size

• Increases with what what can go with it ..
  • dysplasia (in situ)
    • At the end a lot can transpire so symptoms is must.

Bladder Diagnosis

• Urinalysis
• CT show masses,
• USEFUL to check the disease.
• can be done with anesthesia.
• musclarity can assist the disease.

Bladder diagnosis and Symptoms

• Cancers are staged that are on tumours.
• Frequency, metastasis, node region
• Invasin and such can cause those issues to flare up.