2 - Urinary System

The kidney maintains homeostasis through

1. filtration,

2. selective reabsorption,

3. secretion,

4. concentration and dilution of urine,

5. electrolyte and

6. acid–base regulation, and endocrine functions.

The nephron consists of

renal corpuscle and tubular system.

Nephrons differ in location and

loop length, contributing to

urine-concentrating ability.

Renal blood flow is _ relative to _

because filtration and tubular processing depend

on an extensive vascular network.

high; organ mass

The filtration barrier consists

principally of

fenestrated endothelium, glomerular basement membrane, and podocyte slit

diaphragms. It restricts cells and most large plasma proteins.

Glomerular barrier injury most characteristically produces

proteinuria.

Severe diffuse glomerular damage can reduce _ and contribute _

filtration and contribute to azotemia and chronic renal dysfunction.

•Persistent protein loss may contribute to

progressive renal injury.

reflect proliferation of intrinsic cells or accumulation of inflammatory cells.

Hypercellularity

when identifying patterns of glomerular injury, what should we remember

•Assess capillary loops, mesangium, urinary space, and basement membranes.

•Record whether the lesion is focal, segmental, diffuse, or global.

•Look for necrosis, fibrin, crescents, synechiae, and sclerosis when present

Inflammatory or immune-mediated glomerular

injury may involve capillary walls, mesangium,

endothelial cells, epithelial cells, and podocytes.

Morphologic pattern is more useful than

prematurely assigning etiology.

GLOMERULONEPHRITIS

represents increased extracellular

matrix with loss or obliteration of functional

capillary loops. It is commonly a marker of

chronic glomerular injury and nephron loss.

GLOMERULOSCLEROSIS

Extracellular amyloid deposition may expand

the glomerular tuft, compress capillary lumina,

and impair filtration. H&E is supportive but not

definitive; Congo red is used for confirmation.

GLOMERULAR AMYLOIDOSIS

have high metabolic

requirements and are exposed to

substances concentrated in tubular fluid.

Tubular epithelial cells

commonly cause tubular injury.

Ischemia and nephrotoxins

ranges from reversible epithelial damage to frank

necrosis. Lesions may be patchy even when renal dysfunction is severe.

ACUTE TUBULAR NECROSIS

Surviving tubular cells can re-enter the cell cycle after injury.

Regenerating cells may

have basophilic cytoplasm, enlarged nuclei,

prominent nucleoli, and mitotic figures.

TUBULAR REGENERATION

FUNCTIONAL CONSEQUENCES OF TUBULAR INJURY

•Reduced sodium and water reabsorption.

•Impaired urine concentration.

•Altered potassium and acid–base handling.

•Potential back-leak or obstruction of tubular fluid

impairs reabsorption and secretion and may reduce urine concentrating ability.

Tubular damage

can contribute to acute kidney injury and azotemia

Severe acute tubular injury

are centered in the renal interstitium and commonly involve tubules

secondarily.

Tubulointerstitial lesions

•Acute lesions of TUBULOINTERSTITIAL DISEASE may include

edema and neutrophils.

•Chronic lesions of TUBULOINTERSTITIAL DISEASE commonly contain

lymphocytes/plasma cells, fibrosis, and tubular atrophy.

may accompany interstitial inflammation during TUBULOINTERSTITIAL DISEASE

•Tubular degeneration or necrosis

commonly produces interstitial fibrosis, tubular atrophy, chronic

inflammation, and progressive nephron loss. In advanced

disease, the original cause may no longer be identifiable.

CHRONIC INTERSTITIAL NEPHRITIS

involves the renal pelvis and renal parenchyma.

Infection may ascend from the lower urinary tract or reach the

kidney hematogenously.

PYELONEPHRITIS

Vascular compromise can produce glomerular and tubular ischemic injury.

Distribution often reflects the affected vascular territory.

•Reduced perfusion can cause tubular injury.

•Severe interruption of blood supply can cause infarction.

•Chronic vascular injury can contribute to fibrosis and nephron loss.

RENAL VASCULAR INJURY

An infarct is tissue necrosis caused by interruption of blood supply.

Grossly it may be wedge-shaped;

microscopically early lesions typically show

ischemic/coagulative necrosis with

preservation of basic architecture.

RENAL INFARCTION

A useful conceptual sequence is loss of functional nephrons followed by adaptive changes and progressive injury.

•Primary injury → nephron loss.

•Surviving nephrons undergo compensatory hypertrophy/hyperfiltration.

•Persistent increased workload can promote further glomerular/tubular injury.

•Interstitial fibrosis and tubular atrophy reduce functional renal mass.

•Compensation eventually becomes inadequate and clinical renal failure develops.

CHRONIC KIDNEY DISEASE

1. Localize the lesion

• Renal tubules (specifically the proximal convoluted tubules).

• Indicated by the loss of the brush border, which is unique to proximal tubular epithelium.

2. Identify the dominant morphologic process

• Acute tubular injury (ATI) / Acute tubular necrosis (ATN).

• Specifically, this is an ischemic injury triggered by prolonged systemic hypotension.

3. Which findings indicate necrosis?

• Epithelial necrosis (direct mention).

• Granular luminal debris (representing sloughed, dead epithelial cell fragments casting into the tubule lumens).

4. What functional consequence would you expect?

• Acute renal failure (ARF) / Acute kidney injury (AKI).

• Mechanistically, this causes an abrupt drop in glomerular filtration rate (GFR), clinical oliguria or anuria, and progressive uremia/azotemia.

5. Formulate a morphologic diagnosis

• Kidney: Tubular necrosis (or degeneration and necrosis), acute, diffuse, severe.

1. Which findings establish chronicity?

• Gross findings: Small and irregular kidneys (indicating parenchymal contraction and scarring over time).

• Histological findings: Interstitial fibrosis (scar tissue formation), tubular atrophy (wasting away of nephron components), and chronic mononuclear inflammation (infiltration of lymphocytes and macrophages rather than neutrophils).

2. How does nephron loss alter renal function?

• Reduced GFR: Loss of functional nephrons directly lowers the total Glomerular Filtration Rate.

• Compensatory hypertrophy: Remaining intact nephrons undergo hyperfiltration and hypertrophy to handle the increased load.

• Loss of concentrating ability: Damaged tubules cannot maintain the medullary osmotic gradient, leading to polyuria (increased urination) and polydipsia (increased thirst).

• Azotemia: The kidneys fail to adequately excrete metabolic waste products, leading to a buildup of blood urea nitrogen (BUN) and creatinine.

• Systemic effects: Secondary consequences often develop, including non-regenerative anemia (due to decreased erythropoietin production) and altered calcium-phosphorus homeostasis (secondary hyperparathyroidism).

3. Why may the initiating cause be difficult to determine?

• End-stage convergence: Many distinct primary renal diseases (e.g., chronic glomerulonephritis, chronic interstitial nephritis, chronic pyelonephritis) result in the same identical, nonspecific end-stage picture of widespread fibrosis and atrophy.

• Chronological delay: By the time clinical signs appear and a biopsy or necropsy is performed, the original inciting agent (such as a previous bacterial infection, toxin, or immune complex) is typically no longer present.

4. Morphologic Diagnosis

• Diagnosis: Kidneys: Nephritis, tubulointerstitial, chronic, diffuse, severe, with interstitial fibrosis and tubular atrophy (commonly referred to as "End-stage kidney" or "Chronic kidney disease").

transport urine from the kidneys to the bladder, where it is stored until voluntary or reflex emptying occurs.

ureters

provides the final pathway for urine elimination.

urethra

lined by urothelium, a specialized transitional epithelium.

urinary bladder

contribute to the permeability barrier and allow the mucosa to

change its apparent thickness as the bladder fills and empties.

superficial umbrella cells of the urinary bladder

Beneath the urothelium is the _, followed by the _

lamina propria, muscular wall.

Inflammation of the urinary bladder.

Acute Cystitis

May result from infection, chemical irritation, trauma, urolithiasis, urinary stasis,

or other causes.

Grossly, the mucosa may be congested, reddened, edematous, friable, or

hemorrhagic.

Histologically, neutrophilic inflammation is often prominent.

Acute Cystitis

Develops when irritation or inflammation persists or recurs.

Lymphocytes and plasma cells commonly predominate, although mixed inflammatory populations may be present.

The bladder mucosa can become thickened, irregular and fibrotic.

Chronic Cystitis

common in chronic cystitis and can create substantial epithelial

thickening.

Reactive urothelial hyperplasia

An inflammatory lesion that can resemble a urinary bladder neoplasm grossly and microscopically.

It is characterized by polypoid mucosal projections supported by edematous, inflamed, and often fibrovascular stroma.

Reactive urothelial hyperplasia may be prominent.

Polypoid Cystitis

May occur at any point from the renal pelvis to the urethral opening.

Causes include uroliths, strictures, congenital abnormalities, inflammatory lesions, blood clots, and neoplasia.

The pathologic consequences depend on the location, completeness, duration, and unilateral or bilateral nature of the obstruction.

Urinary Obstruction

dilation of the ureter caused by impaired urine outflow.

Hydroureter

refers to dilation of the renal pelvis

and associated progressive atrophy of renal

parenchyma.

Hydronephrosis

Formation of mineralized or otherwise organized

concretions within the urinary tract.

Urolithiasis

favored by supersaturation of urine,

appropriate physicochemical conditions for crystal

formation, retention of crystals, and failure of normal

inhibitory mechanisms.

Stone formation

can influence stone formation depending

on composition.

Diet, urine pH, infection, metabolism, genetics, and urinary stasis

• A bladder containing uroliths often develops chronic mucosal irritation.

• Histologically, there may be epithelial erosion, ulceration, hemorrhage, edema, neutrophilic or mixed inflammation, and reactive epithelial hyperplasia.

• Chronic irritation can produce fibrosis and polypoid mucosal lesions

Cystitis Associated with Urolithiasis

clinically important because they can produce persistent hematuria,

irritative lower urinary tract signs, obstruction, and local invasion.

Urinary bladder tumors

a major diagnostic consideration in dogs with a bladder mass, but

inflammation and reactive lesions can produce similar clinical and gross findings.

Urothelial tumors

may be papillary, solid, or infiltrative.

Urothelial carcinoma

may show loss of orderly maturation, increased nuclear-to- cytoplasmic ratios, nuclear enlargement, anisokaryosis, prominent nucleoli, and increased mitotic activity.

neoplastic epithelium

multiple papillary, exophytic, frond-like, or polypoid mass

projecting into the lumen from the mucosal surface

Irregular nests and sheets of malignant cells breaching

the lamina propria and muscularis propria.

Urothelial carcinoma

basahin mo lang, come up with a trend or story line

consider inflammation, urolithiasis, trauma, vascular injury, and neoplasia.

•Hematuria

consider cystitis, urethral obstruction, and painful urolithiasis.

•Dysuria/stranguria

commonly reflects lower urinary tract irritation.

•Pollakiuria

investigate obstruction and its level.

•Hydronephrosis

distinguish polypoid/reactive lesions from urothelial and other neoplasms

•Bladder mass

polypoid cystitis

cystitis assocaited with uroliths