Block 7 Fall 2024 Kidney Pathology Exam PDF

# Block 7 Fall 2024 Kidney Pathology Exam ## Teaching Assistant * David Salinas Aguirre * Keyshla M. Morales Muñoz * Irmaris López López * Carisa O. Jiménez Chaparro ## Nephritic Syndrome * Slides created by: Keyshla M. Morales Muñoz * Edited by: David S ## Glomerular Diseases | Type | Etiology...

# Block 7 Fall 2024 Kidney Pathology Exam ## Teaching Assistant * David Salinas Aguirre * Keyshla M. Morales Muñoz * Irmaris López López * Carisa O. Jiménez Chaparro ## Nephritic Syndrome * Slides created by: Keyshla M. Morales Muñoz * Edited by: David S ## Glomerular Diseases | Type | Etiology | Clinical Presentation | Examples | |---|---|---|---| | Nephritic syndrome |Glomerular inflammation → GBM damage → loss of RBCs into urine → dysmorphic RBCs, hematuria |Hematuria, RBC casts in urine + GFR → oliguria, azotemia ↑ renin release, HTN Proteinuria often in the subnephrotic range (< 3.5 g/day) but in severe cases may be in nephrotic range |Infection-associated glomerulonephritis Goodpasture syndrome IgA nephropathy (Berger disease) Alport syndrome Membranoproliferative glomerulonephritis | Nephrotic syndrome | Podocyte damage impaired charge barrier → proteinuria |Massive proteinuria (> 3.5 g/day) with edema, hypoalbuminemia → ↑ hepatic lipogenesis → hypercholesterolemia Frothy urine with fatty casts Associated with hypercoagulable state due to antithrombin III loss in urine and ↑ risk of infection (loss of IgGs in urine and soft tissue compromise by edema) |May be 1º (eg, direct podocyte damage) or 2º (podocyte damage from systemic process): Focal segmental glomerulosclerosis (1° or 2°) • Minimal change disease (1° or 2°) Membranous nephropathy ( 1° or 2°) Amyloidosis (2°) Diabetic glomerulonephropathy (2°) | ## Casts in Urine * Presence of casts indicates that hematuria/pyuria is of glomerular or renal tubular origin. * Bladder cancer, kidney stones → hematuria, no casts. * Acute cystitis → pyuria, no casts. * All casts contain a matrix composed primarily of Tamm-Horsfall mucoprotein (uromodulin), secreted by renal tubular cells to prevent UTIs. | Cast Type | Description | |---|---| | RBC casts |Glomerulonephritis, hypertensive emergency. | | WBC casts |Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection. | | Granular casts |Acute tubular necrosis (ATN). Can be "muddy brown" in appearance. | | Fatty casts ("oval fat bodies") | Nephrotic syndrome. Associated with "Maltese cross" sign | | Waxy casts |End-stage renal disease/chronic kidney disease. | | Hyaline casts | Nonspecific, can be a normal finding with dehydration, exercise, or diuretic therapy. | ## Nephritic Syndrome * Inflammatory response → disrupts GBM → loss of renally excreted RBCs (acanthocytes) and ↓ GFR → hematuria, oliguria, azotemia, ↑ renin → edema and HTN * Conditions including autoimmune, hereditary, and infectious diseases can cause nephritic Syndrome * Manifest with varying degrees of severity, ranging from asymptomatic hematuria to systemic involvement, as in rapidly progressive glomerulonephritis. * The urine sediment is typically characterized by red blood cell casts, mild to moderate proteinuria (< 3.5 g/day), and sterile pyuria, oligouria and azotemia. * Remember: Hematuria with acanthocytes, RBC casts in urine, Proteinuria (< 3.5 g/24 h), Hypertension. ## Post Streptococcal GN * Type III HSR to GAS β-hemolytic (nephritis strain) after GAS pharyngitis (1-2 weeks after) or GAS impetigo (3-6 weeks after). In adults Staphylococcus can cause it. * Symptoms: edema (periorbital, peripheral), HTN, Coke urine & HF (adults). * Children 3-12yrs: self-limiting & Elderly: RPGN → renal insufficiency * ASO (antistrep O), ADB (Anti-Dnase B titer) * ↓ C3/CH50 (Consumption) because pyrogenic exotoxin B enters circulation and localizes to glomeruli and activates complement * **LM**: Hypercellular / Enlarged glomeruli * **IF**: granular subepithelial immune complex depositions IgG, IgM, C3 across GBM-> Starry sky, lumpy bumpy * **EM**: dome-shaped subepithelial immune complex deposits (humps) * **Tx**. benzathine penicillin or cephalosporins ## IgA nephropathy (Berger's) * Mesangial proliferative GN with diffuse IgA mesangial deposition * Most common Idiopathic, Nephritic Sx.-> Males in their 20s 30s from Asia. * Asymptomatic microhematuria with intermittent gross hematuria during or directly after one or more of the following: post URT infection, Gl infection and strenuous exercise. * ↑ Serum IgA and Normal C3 complement levels * Renal pathology findings of IgA vasculitis * **LM**: mesangial proliferation * **IF**: mesangial IgA immune complex deposits * **EM**: mesangial immune complex deposits * **Tx**: methylprednisona or prednisone ## Alport Syndrome * 85% x-linked dominant M > F and 15% AR Type IV collagen gene mutation 3-a4-a5 network. * Associated with sensorineural hearing loss and abnormalities of the eye (anterior lenticonus, retinopathy) * Often leads to ESRD * Findings: Persistent microhematuria with intermittent gross hematuria, proteinuria and HTN. * **EM**: splitting and alternating thickening and thinning of the glomerular basement membrane (basket-weave appearance). * **IF**: Initially negative, but later Irregular IgG, IgM and C3. ## Rapid progressive GN * Proliferative cellular response and lymphocytic infilitration in bowman space-> crescent -> adhesions between Bowman's space and glomerular tuft. * Crescent formation (moon-shaped) made of plasma proteins like C3b and fibrin * Renal function declines rapidly over days to weeks * Not a disease entity itself but a possible manifestation of glomerulonephritis (Multiple causes) * Poor prognosis: can progress to ESRD within weeks to months * Can be caused by a variety of diseases categorized in three groups according to their IM pattern * **Linear**: Goodpasture syndrome (anti-GBM disease) (Type II) * **Granular** (immune complex RPGN) by Poststreptococcal Glomerulonephritis (Type III) * **Diffuse proliferative glomerulonephritis(most common with SLE)** (Type III) * **Negative** (pauci-immune RPGN) by Vasculitis (Type III) ## Diffuse proliferative glomerulonephritis (DPGN) * Most common and severe manifestation of lupus nephritis in systemic lupus erythematosus(SLE). Also see in others autoimmune disease. * Can be nephritic with nephrotic-range proteinuria * Can lead to immune complex RPGN * ↓ Serum C3 complementlevels & ANA, anti-dsDNA antibodies * **LM**: Thickening of glomerular capillaries (wire loops) * Characterized by increased glomerular cellularity in more than half of the glomeruli (mesangeal and endothelial proliferation) * **IM**: granular appearance * **EM**: Most commonly subendothelial immune deposits (IgG immune complexes, C3, and C1q) * Less commonly subepithelial or intramembranous deposits. ## Membranous Proliferative Glomerulonephritis * Pattern of glomerular injury from subendothelial and mesangial immune complex deposition and/or complement factor * **Type 1**: mesangial and subendothelial deposits (HBV & HCV) * **Type 2 (DDD)**: dense deposit disease in mesangial and intramembranous (BM) area in EM. (IgG Ab that stabilizes C3 convertase-> persistent activation) -> Decrease serum C3 * **Type 3**: subendothelial, intramembranous and subepithelial in EM * Nephritic, nephrotic if severe, concomitant nephrotic-range proteinuria * **LM**: mesangial ingrowth, which leads to thickening and splitting of the glomerular BM (tram-track appearance) * **Hallmark**: duplication of BM ## Tubulointerstitial * Slides created by: Ruben * Edited by: David ## Definition * **Acute Tubular Injury/Necrosis** * ATI is characterized by acute renal failure and often, but not invariably, morphologic evidence of tubular injury, in the form of necrosis of tubular epithelial cells * Not always necrotic so injury preferred term * Most common cause of acute kidney injury * Reversible process ## Causes * Ischemia due to interrupted or decreased blood flow – Ischemic ATI Pattern * Period of inadequate blood flow to the peripheral organs, accompanied by marked hypotension and shock * Direct toxic injury to tubules (endogenous or exogenous agents) – Nephrotoxic ATI Pattern * Caused by a multitude toxic agents * Mixed Patterns occur * i.e. mismatched blood transfusions, skeletal muscle injuries ## Pathogenesis * **Tubular Injury** * Proximal tubules most sensitive * High risk for injury due to toxin concentrating abilities and high energy demand * Early reversible alteration is loss of polarity due to redistribution of transport proteins * Tubuloglomerular feedback in response to increased sodium delivery to distal tubules results in lower GFR * Recruitment of leukocytes/inflammation occurs and exacerbates injury * Later changes are detachment of cells and subsequent luminal obstruction --. Increased intratubular pressure → decreases GFR further * Leaking of tubular filtrate into interstitium due to damaged endothelial cells results in increased interstitium pressure and further damage to tubules and decreased GFR * **Persistent and severe disturbances to blood flow** * Intrarenal vasoconstriction reduces GFR further → decreased blood flow and oxygen delivery * Increased endothelin and reduced nitric oxide and prostacyclin (prostaglandin 12) production ## Reversibility * Patchiness of damage allows non-damaged segments to repair and maintain renal function once disturbance removed * Proliferation and differentiation of epithelial cells allows reversibility (re-epithelialization) ## Clinical Features 1. Initiation Phase 36 hours: slight decline in urine output and increase in BUN; oliguria due to decrease in blood flow and decreasing GFR 2. Maintenance Phase; sustained decrease in urine, salt and water overload, rising BUN concentrations, hyperkalemia, metabolic acidosis. Reversible stage 3. Recovery Phase: steady increase in urine; large amounts of water, sodium, and potassium are lost in the flood of urine due to damage; hypokalemia arises; increased infection risk; creatinine and BUN begin to return to normal; subtle persistent functional impairment for months but eventually complete recovery occurs ## Tubulointerstitial Nephritis * This group of renal diseases involves inflammatory injuries of the tubules and interstitium that are often insidious in onset and are principally manifest by azotemia. * Acute: rapid clinical onset and is characterized histologically by interstitial edema, often accompanied by leukocytic infiltration of the interstitium and tubules, and tubular injury * Chronic: there is infiltra- tion with predominantly mononuclear leukocytes, prominent interstitial fibrosis, and widespread tubular atrophy ## Causes * Focus on pyelonephritis and toxin-induced tubulointerstitial nephritis ## Pyelonephritis * Pyelonephritis is one of the most common diseases of the kidney and is defined as inflammation affecting the tubules, interstitium, and renal pelvis * Acute: due to infection (bacterial)/UTI * Chronic: infection + vesicoureteral reflux + obstruction → repeat episodes * Affects bladder (cystitis), kidney and collecting ducts (pyelonephritis) * Lower UTI may remain localized to bladder or spread to kidney ## Pathogenesis * More than 85% of urinary tract infections are caused by the gram-negative bacilli that are normal inhabitants of the intestinal tract * most common is Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter and * Streptococcus faecalis, also of enteric origin, staphylococci, and virtually every other bacterial and fungal agent can also cause lower urinary tract and renal infection * Polyomavirus, cytomegalovirus, and adenovirus in viral causes → kidney allografts, immunocompromised * Two routes: lower UTI spread > hematogenous ## UTI Ascending Infection 1. Colonization of distal urethra and introitus (female) by coliform bacteria 2. Spread from urethra to bladder * Catheterization common cause * More common in females due to shorter urethra 3. Bladder to kidney spread influenced by * Urinary tract obstruction and urine stasis * Vesicoureteral reflux impairment → valve allows for retrograde urine movement → its absence prevent progression to pyelonephritis * Impairment can be congenital, promoted by bacterial infection, SCI * Intrarenal reflux → open ducts at the tips of the papillae ## Clinical Features - Risk Factors * Urinary tract obstruction * Instrumentation * Vesicoureteral reflux * Pregnancy * Gender and age * Preexisting renal lesions * Diabetes * Immunosuppression and immunodeficiency ## Clinical Features * Sudden onset of pain at the costovertebral angle * Systemic evidence of infection, such as fever and malaise * Bladder and urethral irritation indications: dysuria, frequency, and urgency * Pyuria - urine with increased leukocyte concentration from inflammatory infiltrate → does not differentiate from lower UTI * Renal casts → indicative of renal involvement because they form in tubules * Infection diagnosed by quantitative urine culture * Antibiotic treatment results in symptom disappearance → recurrent infections may occur * Viral causes polyomavirus nephropathy: * nuclear enlargement and intranuclear inclusions visible by light microscopy * interstitial inflammatory response * Treatment consists of a reduction in immunosuppression ## Complications * urinary obstruction, diabetes mellitus, or immunodeficiency results in more serious manifestations and increased risk of repeat infections * Papillary necrosis may result in acute renal failure