Etiology and Pathogenesis of Uremia

Uremia occurs when nitrogenous waste products and other toxins accumulate in the body due to impaired renal excretion, leading to disturbances in fluid-electrolyte and acid-base balance, as well as multi-organ dysfunction.

1. Digestive System

Urea excreted into the gastrointestinal tract is converted to ammonia by bacterial urease, irritating mucosal membranes and causing fibrinous inflammation, ulcers, or bleeding. Lesions may affect the entire GI tract (esophagitis, gastritis, colitis), manifesting as nausea, vomiting, abdominal pain, diarrhea, or hematochezia.

2. Cardiovascular and Pulmonary Systems

• Hypertension from sodium retention and renal ischemia can lead to heart failure.
• Uremic toxins induce fibrinous pericarditis/pleuritis (auscultation reveals friction rubs).
• Pulmonary edema (from heart failure) or uremic pneumonitis (characterized by fibrinous exudates in alveoli) may occur.

3. Hematopoietic System

Anemia results from:
① Decreased erythropoietin production.
② Bone marrow suppression by phenols and hemolysis by guanidines.
③ Iron deficiency due to loss of transferrin in urine.

Bleeding tendencies (e.g., epistaxis, gum bleeding) arise from:
① Thrombocytopenia.
② Platelet dysfunction caused by guanidine toxins.

4. Skeletal System

Hypocalcemia occurs due to:
① Hyperphosphatemia (reduced renal phosphate excretion).
② Calcium binding to phosphate in the gut.
③ Impaired 1,25-dihydroxycholecalciferol synthesis (vitamin D activation).

Chronic hypocalcemia triggers secondary hyperparathyroidism, causing renal osteodystrophy (osteomalacia/fibrous osteitis).

5. Skin

• Gray-yellow discoloration (anemia + urochrome deposition).
• Uremic frost (urea crystal deposits on skin).
• Pruritus (possibly due to urea-induced nerve irritation).

6. Nervous System

• Cerebral edema from urea accumulation, with petechiae or microinfarcts.
• Neurotoxins cause neuronal degeneration, leading to lethargy, seizures, or coma.
• Peripheral neuropathy (numbness, burning sensations) may link to methylguanidine.

Pathogenic Mechanisms

Uremia arises from combined effects of multiple toxins (e.g., urea, guanidines), not a single agent.