SEARCH RESULTS FOR: Pyelonephritis

Vesicoureteric reflux (VUR): Pathogenesis and clinical findings

Vesicoureteric reflux (VUR): Pathogenesis and clinical findings Authors: Nicola Adderley Reviewers: Emily Ryznar *Lindsay Long * MD at time of publication Abnormal function Abnormal anatomy Neurogenic bladder (e.g. cerebral palsy, constipation, spinal injury, iatrogenic) Non-neurogenic bladder (neuropsychological) Lower urinary tract abnormality (posterior urethral valves, meatal stenosis) Bladder outlet obstruction ↑ pressure distorts UVJ Upper urinary tract abnormality (ureters) UVJ abnormality Incomplete closure of UVJ during bladder contraction Abbreviations • UVJ - ureterovesicular junction • UTI – urinary tract infection Failure of bladder sphincter to relax during bladder contraction Vesicoureteric reflux (VUR): Back flow of urine from the bladder into one or both ureters +/- kidneys Migration of lower urinary tract bacteria to kidneys Bacterial invasion of renal parenchyma Upper UTI (pyelonephritis) Incomplete emptying of bladder during Abnormal ↑ pressure in bladder Bladder dilates Dilated bladder on U/S urination Bacteria in bladder are not cleared during urination voiding habits ↑ bladder capacity Renal scarring ↓ functional renal tissue *Chronic kidney disease (↓ GFR, hypertension, proteinuria) Flank tenderness Fever, dysuria, urgency, frequency Lower UTI (cystitis) Urinary stasis Cloudy, foul- smelling urine Urethral stricture Notes Urgency, dysuria, frequency • First febrile UTI in an infant should trigger a work-up for VUR • High likelihood of spontaneous resolution • *Late complication of severe VUR Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 19, 2018 on www.thecalgaryguide.com

autosomal-dominant-polycystic-kidney-disease-adpkd

Autosomal Dominant Polycystic Kidney Disease (ADPKD): Pathogenesis, Clinical Findings, and Complications Author: Yan Yu* Reviewers: David Waldner* Sean Spence* Andrew Wade* * MD at time of publication Legend: Published April 14, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications thecalgaryguide.com One theory (mechanism unclear): these mutations in the polycystin gene result in dysfunctional Ca2+ channels on epithelial cells PKD1 mutation (~78%) Abnormal Ca2+ entry disrupts intracellular Ca2+ signaling In the Kidney: all segments of the nephron develop cysts: sacs of flattened epithelium filled with proteinaceous fluid, replacing normal parenchyma with dysfunctional tissue PKD2 mutation (~15%) Expansive cell proliferation Low urine Osmolality (< 500 mmol/kg) Abnormally expandable basement membranes PKD3 mutation (rare) ↑ fluid secretion 95% inherited, autosomal dominant mutations 5% spontaneous mutations In adults, the same pathophysiology occurs in epithelial tissue throughout the body When pH of urine <5.5, uric acid is in its protonated form & is less soluble àprecipitates uric acid stones Nephrolithiasis Urine accumulates within cysts Cyst growth Pyelonephritis Damaged tubules leak proteins into filtrate Proteinuria Flank pain Inability to concentrate urine Low urine specific gravity (<1.010) ¯ NH3 production, ↑ acidity of renal tubule (¯ pH) Activates nociceptors Cyst hemorrhage Urine stasis à precipitation of CaOxalate stones within cysts Multiple Renal Cysts (bilaterally, in cortex and medulla, on Ultrasound) In the Brain: expansion & weakening of cerebral arterial walls “Berry Aneurysms” 9- 12% (ask about this on Family Hx!) In many organs: epithelial tissue expansion & fluid secretion In the Heart: abnormal valve collagen matrix Valve prolapse & regurgitation Liver (90%), spleen/pancreas (5-10%), thyroid (rare) cysts In seminal vesicles: Cyst formation disrupts sperm motility Infertility In GI tract: Cyst formation Herniations, diverticuli Dysfunctional collecting ducts Abdominal mass (enlarged kidneys) (may be palpable) Blood leaks into renal tubules Hematuria (isomorphic) Bacteria accumulate in the static urine Dysfunctional proximal tubules Unknown mechanisms à ¯ urine citrate àmore urine Ca2+ binds to oxalate than to citrate à↑ Ca- Oxalate stones Note: PKD1 mutations have more severe prognosis than PKD2 mutations (earlier disease onset, larger cysts) Vessels tear more easily Stretches renal capsule Cysts compress renal vasculature ¯ Glomerular perfusion To ↑ perfusion à kidneys activate RAAS Hypertension

GU-changes-in-pregnancy

Physiologic Changes in Pregnancy: Renal & Genitourinary Pregnancy ↑ estrogen ↑ angiotensin synthesis in liver Renin-angiotensin- aldosterone system activation ↑ aldosterone ↑ plasma volume ↑ glomerular filtration rate (GFR) Mechanism unclear, possibly 1) ↑ circulating anti- angiogenic factorsà ↑ permeability of glomerular basement membrane, or 2) ↑ plasma volumeà↓ oncotic pressure of plasma at the glomerulus Proteinuria > 300 mg/day, abnormal in pregnancy ↑ hCG level Dilation of renal vasculature ↑ renal vascular & interstitial volume ↑ filtration surface area Overwhelming load of glucose to proximal tubule ↑ urine output ↑ relaxin secreted by placenta Mechanism not well understood ↓ osmotic threshold for ADH release & thirst ↑ ADH secretion & ↑ oral hydration Incomplete reabsorption of glucose Glucosuria Encourage bacterial growth in the urine Urinary tract infection (e.g. cystitis, pyelonephritis) ↑ serum progesterone Uterine rotation as uterus enlarge due to presence of large bowel Ureter compression (R > L) Ureterovesical reflux (back-flow of urine into the ureters/kidneys) Dilatation of ureters (R > L) (hydroureter) & renal pelvis (hydronephrosis) Progesterone competes with aldosterone ↓ sodium reabsorption ↓ plasma sodium concentration Hyponatremia of pregnancy* (pathological if < 130 mEq/L) *Despite factors favoring sodium excretion, there is a net retention of sodium during pregnancy from adaptation of the renal tubules ↑ urinary stasis ↑ excretion of creatinine and urea in urine ↓ serum creatinine and urea ↓ ureteral toneà ↑potential for ureter dilation Mechanism not well understood ↓ peristalsis of ureters ↑ urinary frequency (voiding > 7x/day) ↑ nocturia (voiding ≥ 2x/night) ↓ oncotic pressure of plasma intra-vascularly àwater leaves blood, enters interstitial tissue, and stays there in gravity-dependent regions of the body Pedal +/- ankle edema Author: Simonne Horwitz Reviewers: Claire Lothian, Crystal Liu, Ronald Cusano*, Candace O’Quinn*, Yan Yu* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 28, 2020 on www.thecalgaryguide.com

Pyelonephritis

Acute Pyelonephritis: Pathogenesis and clinical findings Female sex Indwelling Diabetes (especially post- urinary catheter mellitus menopausal due to loss of protective Lactobacillus species) Obstruction of bladder outlet (congenital/acquired) High blood glucose damages nerves controlling the bladder, as well as blood vessels supplying bladder nerves Glycosuria (elevated levels of glucose in urine) create nutritive environment for bacterial growth Excessive urine buildup increases pressure exerted against the bladder, pushing urine from bladder up to ureters Authors: Sergio F. Sharif Reviewers: Michelle J. Chen Jessica Revington Yan Yu* Juliya Hemmett* Brandon Christensen* * MD at time of publication Shorter urethra allows for fecal microbes to more readily enter the urinary tract Catheter inoculates deep urinary tract with bacteria & facilitates organisms to enter bladder Neurogenic bladder (decreased bladder control due to nerve damage) is unable to appropriately release urine, leading to urinary retention & failure to clear residing bacteria Bacteremia (bacterial infection in bloodstream) Bacteria initially colonize the lower urinary tract, then migrate up the tract towards one or both kidneys (most commonly Gram-negative rods, e.g., Escherichia coli) Bacteria, such as Staphylococcus species, spread from another site of infection to kidneys via bloodstream Acute Pyelonephritis Inflammation of the kidney interstitium due to upper urinary tract infection, usually bacterial Collective contribution of mechanisms stated below, if severe Sepsis** Concurrent cystitis irritates urinary tract (see lower UTI slide)** Bacteria expressing virulence factors (e.g., P fimbriae in Escherichia coli) exploit host susceptibility & infect upper urinary tract (ureters & kidneys) Positive urine culture Dysuria (pain & burning while urinating) Bacteria trigger IL-8 release by local immune cells in the upper urinary tract, triggering recruitment of neutrophils to renal tubules & interstitium Neutrophils degranulate in the infected tissue, phagocytose bacteria & form sacrificial neutrophil extracellular traps (resulting in neutrophil death) in attempt to clear infection Neutrophil-mediated immune response damages surrounding kidney tissue (tubular injury) Acute kidney injury** Immune cells at the site of infection release cytokines (e.g., IL-1, TNF), which disseminate systemically Cytokines act in the brain in concert with unclear mechanisms relating to tissue injury & inflammation triggered by infection (see Neurotransmitters & Pharmacology behind Nausea and Vomiting slide**) Cytokines bind receptors in the anterior hypothalamus, triggering pathways ultimately leading to heat-generating responses (e.g., shivering) Cytokines promote the growth & release of white blood cells from bone marrow into bloodstream Dead neutrophils collect in renal tubules near infection & attach to assemblies of mucoprotein (a renal tubular epithelium protein secreted into tubules) Pyuria (WBCs in urine) Nausea/vomiting Fever Leukocytosis (↑ WBCs) Urine white blood cell (WBC) casts (cylindrical particles with WBCs seen on microscopy) Costovertebral Flank pain CT KUB - angle tenderness findings may include focal or diffuse involvement, fat stranding, gas formation, &/or other complications including renal scarring **See corresponding and abscesses Calgary Guide slide(s) Complications Published November 23, 2025 on www.thecalgaryguide.com Unclear mechanism involving systemic inflammation worsens mental status in susceptible individuals Altered level of consciousness (especially in elderly) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding