What is the role of parenchyma in organ function and how is it preserved?

Parenchyma: Role in Organ Function and Preservation

Definition and Functional Role

Parenchyma represents the functional tissue of an organ—the cells that perform the organ's essential physiological work—as distinct from the supporting stromal framework of connective tissue, blood vessels, and structural elements. 1

Organ-Specific Parenchymal Functions

• In the lungs, parenchyma consists of thin-walled alveoli that create an enormous surface area for gas exchange, held open by transpulmonary pressure and balanced by tissue forces and alveolar surface film forces 1, 2
• In the kidneys, parenchyma includes the nephrons (glomeruli and tubules) that filter blood, reabsorb essential substances, and produce urine 1
• In the liver, parenchyma comprises hepatocytes that perform metabolic, synthetic, and detoxification functions 1

Quantitative Importance

• Lung parenchyma constitutes approximately 90% of lung tissue volume, with non-parenchymal structures (bronchi, vessels >1mm diameter) representing only ~10% 1
• The inflated lung consists mostly of air, with only 10-15% being actual tissue (cells, fibers, matrix) and blood 1

Mechanisms of Parenchymal Preservation

Surgical Preservation Strategies

In renal surgery, nephron-sparing approaches (partial nephrectomy) should be prioritized over radical nephrectomy for all patients with solid renal masses ≤4 cm, and especially for those with solitary kidney, bilateral tumors, familial RCC, pre-existing CKD, or proteinuria. 1, 3

Technical Approaches to Maximize Parenchymal Preservation

• Tumor enucleation removes only the tumor with its pseudocapsule, preserving maximal parenchyma, and should be considered in patients with familial RCC, multifocal disease, or severe CKD 1
• Minimal surgical margins (thin layer of healthy parenchyma) are appropriate to avoid local recurrence while maximizing preservation 1
• Warm ischemia time should be kept ideally below 25-30 minutes during clamped partial nephrectomy to minimize ischemic injury to preserved parenchyma 3, 4, 5

Critical Caveat on Ischemic Injury

• Histologic deterioration of preserved renal parenchyma after partial nephrectomy occurs in 72% of patients, with 45% experiencing substantial increases in chronic kidney disease scores 5
• However, this deterioration correlates primarily with pre-existing comorbidities (hypertension, diabetes, CKD) rather than ischemia duration, suggesting that conventional ischemia times have limited impact on long-term parenchymal health 5
• Patients with hypertension/diabetes/CKD have 3.53 times higher odds of substantial histologic deterioration compared to those without these comorbidities 5

Distinguishing Parenchyma from Reactive Changes

In pathologic assessment, preserved underlying alveolar architecture distinguishes reactive non-neoplastic parenchyma from tumor bed, while destroyed lung architecture indicates tumor involvement. 1

Key Histologic Features

• Reactive non-neoplastic parenchyma shows preserved architecture with interstitial thickening by fibrosis and inflammation, evenly spaced entrapped hyperplastic epithelium (pneumocytes, bronchiolar epithelium), and organizing pneumonia 1
• Tumor bed demonstrates destroyed parenchymal architecture, with components including viable tumor, necrosis, and stromal tissue (fibrosis plus inflammation) 1
• Dense fibrosis or organizing pneumonia can appear grossly similar to viable tumor, requiring microscopic correlation to accurately measure tumor bed size versus reactive parenchymal changes 1

Parenchymal Support and Regeneration

Mesenchymal-Parenchymal Interactions

• Mesenchymal stromal cells (MSCs) in perivascular compartments secrete factors that support parenchymal cell survival, proliferation, and functional activity through paracrine effects or direct cell-to-cell contact 6
• MSCs provide supportive microenvironment specifically for primitive stem/progenitor populations, functioning as "stem/progenitor niche" forming cells 6
• The Alx3-Wnt3a developmental axis enables postnatal progenitors to regenerate both parenchymal and stromal tissues when pivotal signals are reinstated in decellularized matrices 7

Fibrosis as Failed Preservation

• Parenchymal organ fibrosis results from prolonged injury, deregulated wound healing, and excessive extracellular matrix deposition, with common mechanisms including transforming growth factor beta signaling and reactive oxygen species generation 8
• Activated myofibroblasts produce excessive fibrous scar and may originate from endogenous cells (hepatic stellate cells, fibroblasts), bone marrow (fibrocytes), or epithelial-to-mesenchymal transition 8

Clinical Assessment of Parenchymal Integrity

Physical Examination

• In hepatic congestion, the liver edge is palpable below the costal margin as enlarged, smooth, tender with firm consistency, with hepatomegaly present in 52.9% of acute hepatitis cases 9
• Hepatojugular reflux (compression over liver causing jugular venous distension) is a specific sign of hepatic congestion 9

Imaging Evaluation

• Abdominal ultrasound is the mandatory first-line imaging when liver parenchymal abnormality is suspected, showing diffuse hypoechogenicity, increased portal vein wall thickness, and "starry sky" appearance in acute inflammation 1, 9
• MRI with contrast assesses parenchymal inflammation showing increased T2 signal, decreased T1 signal, and heterogeneous perfusion in inflamed parenchyma 1
• Image-guided liver biopsy should be considered in patients with small livers difficult to percuss, obese patients, and those with ascites to ensure adequate parenchymal sampling 1