Renal & Gastrointestinal Pathophysiology Review

Urinary Tract Infection (Acute Cystitis)

• Definition: Infection that can occur anywhere along the urinary tract, most commonly at the bladder; infection is typically ascending (micro-organisms enter at the distal urethra and travel upward).
• Most common pathogen: E. coli.
• Pathophysiology
• Microbes enter at the urethral meatus → ascend toward bladder.
• Women at higher risk due to short urethra & close proximity of urethra to anus.
• Mechanical obstructions ↑ risk: renal calculi, enlarged prostate, indwelling catheters.
• Results in epithelial cell necrosis & local inflammatory response.
• Clinical Manifestations
• Dysuria (pain/burning on urination).
• Urgency & frequency (polyuria of small volumes).
• Hematuria (visible or microscopic blood).
• Purulent exudate → cloudy, foul-smelling urine.
• Systemic signs possible: low-grade fever, malaise.
• Potential Complications
• Ascending spread → pyelonephritis.
• Sepsis in vulnerable hosts (elderly, immunocompromised).

Pyelonephritis (Acute & Chronic)

• Definition: Infection-induced inflammation of renal parenchyma; may be acute or evolve into chronic, scarring disease.
• Typical pathogen: E. coli (ascends from lower tract).
• Pathophysiology
• Bacteria ascend ureters → reach nephrons.
• Inflammatory exudate + edema compress tubules → impaired filtration.
• Repeated/untreated episodes → fibrosis & scarring → chronic pyelonephritis.
• Risk Factors
• Urinary obstruction (renal calculi, strictures, tumors, BPH).
• Incomplete bladder emptying (neurogenic bladder, pregnancy).
• Frequent intercourse (introduces bacteria; especially in women).
• Exposure to STIs, hormonal changes (↓ estrogen at menopause) that weaken ureteral peristalsis.
• Clinical Manifestations
• Flank (costovertebral angle) pain.
• Fever, chills, malaise, nausea/vomiting.
• Dysuria, frequency, urgency (+/- symptoms of cystitis).
• Lab: bacteriuria, pyuria, possible mild proteinuria.
• Complications: abscess, urosepsis, chronic kidney damage → chronic kidney disease (CKD).

Chronic Kidney Disease (CKD)

• Definition: Progressive, irreversible loss of nephron function; waste products accumulate because filtration fails.
• Most common etiologies: \text{HTN} & diabetes mellitus.
• Pathophysiology
• Chronic injury → nephron destruction → compensatory hyperfiltration in remaining nephrons → progressive decline in \text{GFR}.
• Accumulation of uremic toxins, disturbances in water, electrolyte, acid–base, hormonal regulation.
• Clinical Manifestations
• Altered K^+ regulation → hyperkalemia (arrhythmia risk).
• Reduced erythropoietin → anemia → ↓ energy, weakness, \text{S.O.B.}, pale mucosa.
• Fluid retention → edema (peripheral, periorbital), pulmonary congestion.
• Hypertension (both cause & consequence).
• Foamy/bubbly urine (proteinuria), nocturia.
• Muscle cramps, pruritus, uremic frost in late stages.
• Course & Management
• Slow decline over years → end-stage renal disease (ESRD).
• Treat underlying cause; control BP, glucose; dietary management.
• Renal replacement: dialysis or transplant when \text{GFR}<15\,\text{mL·min}^{-1}.

Urolithiasis (Renal Calculi)

• Definition: Formation of calculi anywhere in urinary tract; more common in males; rising incidence with obesity & type 2 diabetes.
• Stone Composition
• ≈ 75% calcium (oxalate, phosphate, or mixed).
• Others: uric acid, struvite (infection), cystine.
• Pathophysiology
• Urinary stasis + supersaturation of solutes (salts, acids) → nucleation → crystal aggregation.
• Risk ↑ with dehydration, hypercalciuria, hyperoxaluria, gout, UTIs.
• Stones may obstruct tubules, ureter, bladder outlet.
• Clinical Manifestations
• Renal Colic: acute, intermittent, radiating (flank → groin) pain due to ureteral peristaltic spasms.
• Non-colic Pain: dull, deep ache from distended renal pelvis/calyces.
• Hematuria, dysuria, urgency, nausea/vomiting, diaphoresis.
• Potential Complications: hydronephrosis, infection, renal impairment.

Urinary Incontinence

• Definition: Accidental or involuntary loss of urine (enuresis in children; in adults, a symptom of underlying dysfunction).
• General Pathophysiology
• Impaired detrusor muscle contraction or over-activity.
• Altered neural pathways (CNS/PNS), ↓ hormonal tone, or mechanical factors.
• Classifications & Key Features
• Stress Incontinence – leakage with ↑ abdominal pressure (cough, sneeze, laugh); weak pelvic floor.
• Urge Incontinence (Overactive Bladder) – detrusor over-activity → strong, sudden urge, nocturia, frequency.
• Overflow Incontinence – bladder outlet obstruction or detrusor under-activity → over-distended bladder leaks.
• Functional Incontinence – normal lower tract but inability to reach toilet (mobility/cognition issues).
• Neurogenic Bladder – disrupted brain–bladder signaling; variable retention or incontinence.
• Impacts: Skin breakdown, infection risk, social isolation, depression.

Polycystic Kidney Disease (PKD)

• Definition: Bilateral growth of fluid-filled cysts within kidney tissue → progressive nephron loss; most common inherited cause of CKD.
• Genetic Categories
• Autosomal Dominant PKD (ADPKD) – adult onset; \approx95\% of cases.
• Autosomal Recessive PKD (ARPKD) – pediatric onset, severe.
• Acquired Cystic Disease – long-term dialysis patients.
• Pathophysiology
• Cysts enlarge (number & size) → compress surrounding parenchyma, obstruct tubular flow.
• Compression of renal vasculature ↓ perfusion → ischemia, fibrosis.
• Progression toward ESRD.
• Clinical Manifestations (often appear in adulthood)
• Early: Enlarged kidneys palpable; uncontrolled hypertension (due to renin–angiotensin activation from ischemia).
• Flank/abdominal pain, heaviness.
• Hematuria, recurrent UTIs, nephrolithiasis.
• Altered fluid/electrolyte balance.
• Extra-renal cysts (liver, pancreas), valvular heart disease, cerebral aneurysms.

Diverticular Disease (Large Intestine)

• Terminology
• Diverticulum – single mucosal out-pouching through muscle layer.
• Diverticula – multiple.
• Diverticulosis – presence of diverticula (often asymptomatic).
• Diverticulitis – inflammation/infection of diverticula (complication).
• Pathophysiology
• Chronic ↑ intraluminal pressure + weak points in sigmoid/descending colon → herniation of mucosa.
• Low-fiber diet, altered motility, obstruction, impaired perfusion contribute.
• Stasis of fecal matter in pouch → bacterial overgrowth → micro-perforation → inflammation.
• Clinical Manifestations of Diverticulitis
• \text{LLQ} abdominal pain (steady, crampy).
• Fever, leukocytosis.
• Nausea, vomiting, change in bowel habits (constipation/diarrhea).
• Possible palpable mass, bloating.
• Complications: Abscess, perforation, peritonitis, fistula, bleeding, bowel obstruction.

Integrative & Comparative Points

• Ascending infections (UTI, pyelonephritis) share common etiologic organism E. coli due to perineal flora proximity.
• Obstruction (stones, enlarged prostate) predisposes both infection and renal parenchymal damage.
• Chronic injuries (CKD, PKD) converge on final pathway of \text{ESRD} requiring renal replacement therapy.
• Electrolyte imbalance, especially K^+, is a recurring safety priority in CKD and acute obstructive uropathies.
• Lifestyle factors (low fiber diet, obesity, DM) modulate risk across multiple systems (stones, diverticulosis, CKD).
• Shared clinical red flags: hematuria, flank pain, fever, changes in urine output warrant prompt evaluation to prevent irreversible damage.