II-10. Organ changes in chronic renal failure

慢性腰不全における臓器の病的変化

Organ Changes in Chronic Renal Failure

Hematopoietic System

RBC: production declines first → normocytic normochromic anemia (↓EPO + BM suppression); later hypochromic microcytic anemia (iron + folate deficiency).
Thrombocytes: ↓production (BM toxicity), ↓function (dysfunctional GP2b3a), ↓coagulation/fibrinolysis proteins → hemorrhagic diathesis (skin petechiae/suffusion, GI bleeding → iron-deficiency anemia).

Immunological

Causes: BM toxicity, catabolic state → immunosuppression (leukopenia, lymphopenia, ↓WBC function) → ↑inflammation, ↑tumor risk.

Bone Metabolism (Renal Osteodystrophy)

Causes: ↑serum phosphate → ↓Ca²⁺ → secondary hyperparathyroidism; ↓pH → phosphate buffer activation → phosphate mobilized from bone; ↓vitamin D3 → secondary hyperparathyroidism → ↑osteoclast → Ca²⁺ liberation.
Consequences: bone/joint/muscle pain, weakness, pathological fractures, hypocalcemia, soft tissue calcification (CaPO₄ → calciphylaxis), osteomalacia (growth retardation in children).

Gastrointestinal

Urea → intestine → urease → cyanic acid (CNS toxicity) + NH₄ (local inflammation/edema). Na⁺/water retention + albumin deficiency worsen edema.
↑Gastrin → ↑HCl → erosions/ulcers (bleed easily with thrombocytopathy). NH₄ → intestinal atonia/paresis → constipation/diarrhea, ↓appetite, weight loss, bloating, nausea/vomiting → malnutrition.

Uremic Lungs

Mucous membrane inflammation: serous (pleuritis, pericarditis), pneumonitis (sterile), pneumonia (bacterial). Lung edema from fluid retention + ↓albumin + ↑vascular permeability.

Nervous System

Early: fatigue, concentration deficit, headache (toxins/cyanic acid). Sleep disorders, depression, confusion → coma; cognitive disorders; peripheral/autonomic neuropathy.
Neuromuscular irritability (↑reflexes): spasms, tremor, restless legs; Chvostek sign (masseter tap), Trousseau sign (BP cuff → hand spasm) — hypocalcemia signs.

Skin

Pruritus (leading symptom; toxins, uric acid, ions, dry skin, anemia, PTH).
Color: pale (anemia), greyish (uropigment). Dry skin/lips/mouth, coated tongue. Urine smell (NH₃). Hemorrhage, nail atrophy, calcinosis cutis, uremic frost (urea crystals). Red eyes (CaPO₄ conjunctivitis, retinopathy).

Cardiorenal Syndrome (CRS)

Combined heart-kidney dysfunction (acute/chronic). Forms: (1) heart-initiated (↓CO → ↓GFR → ↑RAAS → Na⁺/water retention), (2) kidney-initiated (AKI/CRF), (3) hemodynamic (ascites → ↑central BP), (4) systemic (sepsis, shock, hepatorenal, amyloidosis, diabetes).

Hepatorenal Syndrome (HRS)

Primary = acute/chronic liver failure; mortality >50%; pre-renal. Type 1 (fast, vasodilation/shock, GFR <20), Type 2 (diuretic-resistant ascites, GFR <40).
Mechanism: ↑portal pressure → splanchnic vasodilation → ↓circulating volume → RAAS → Na⁺/water retention → worsens ascites; severe → renal vasoconstriction (HRS-1 = hypoxic AKI).

一問一答

▶How does anemia evolve in chronic renal failure?

RBC production declines first → normocytic normochromic anemia (↓EPO + BM suppression); later hypochromic microcytic anemia (iron + folate deficiency).

▶Why does hemorrhagic diathesis develop in chronic renal failure?

↓Platelet production (BM toxicity), ↓platelet function (dysfunctional GP2b3a), and ↓coagulation/fibrinolysis proteins cause bleeding (petechiae, GI bleeding → iron-deficiency anemia).

▶How does chronic renal failure affect immunity?

BM toxicity and the catabolic state cause immunosuppression (leukopenia, lymphopenia, ↓WBC function) → ↑inflammation and ↑tumor risk.

▶What are the consequences of renal osteodystrophy?

Bone/joint/muscle pain, weakness, pathological fractures, hypocalcemia, soft-tissue calcification (CaPO₄ → calciphylaxis), and osteomalacia (growth retardation in children).

▶What causes renal osteodystrophy?

↑Serum phosphate → ↓Ca²⁺ → secondary hyperparathyroidism; acidosis mobilizes phosphate from bone; ↓vitamin D3 → secondary hyperparathyroidism → ↑osteoclast activity → Ca²⁺ liberation.

▶How does uremia affect the GI tract?

Urea → urease → cyanic acid (CNS toxic) + NH₄ (local inflammation/edema); ↑gastrin → ↑HCl → erosions/ulcers (bleed easily), and NH₄ → intestinal atonia (constipation/diarrhea, ↓appetite, nausea) → malnutrition.

▶What are the pulmonary manifestations of uremia?

Serous mucous membrane inflammation (pleuritis, pericarditis), sterile pneumonitis, bacterial pneumonia, and lung edema (from fluid retention + ↓albumin + ↑vascular permeability).

▶What neurological effects occur in chronic renal failure?

Early fatigue, concentration deficit, headache (toxins/cyanic acid), then sleep disorders, depression, confusion → coma, cognitive disorders, and peripheral/autonomic neuropathy.

▶What are the Chvostek and Trousseau signs, and what do they indicate?

Neuromuscular irritability signs of hypocalcemia: Chvostek (masseter twitch on tapping the facial nerve) and Trousseau (hand spasm with a BP cuff).

▶What is the leading skin symptom in chronic renal failure and its causes?

Pruritus — caused by toxins, uric acid, ions, dry skin, anemia, and PTH.

▶What is uremic frost?

Deposition of urea crystals on the skin in advanced uremia.

▶What is cardiorenal syndrome and its four forms?

Combined heart-kidney dysfunction: (1) heart-initiated (↓CO → ↓GFR → ↑RAAS), (2) kidney-initiated (AKI/CRF), (3) hemodynamic (ascites → ↑central BP), (4) systemic (sepsis, shock, hepatorenal, amyloidosis, diabetes).

▶What is hepatorenal syndrome and its mechanism?

Pre-renal kidney failure from acute/chronic liver failure (mortality >50%): ↑portal pressure → splanchnic vasodilation → ↓circulating volume → RAAS → Na⁺/water retention (worsens ascites); severe → renal vasoconstriction.

▶How do type 1 and type 2 hepatorenal syndrome differ?

Type 1: fast, with vasodilation/shock and GFR <20. Type 2: diuretic-resistant ascites with GFR <40.

▶What causes the skin color changes in chronic renal failure?

Pallor (anemia) and a greyish tint (uropigment); also dry skin, urine smell (NH₃), hemorrhage, nail atrophy, calcinosis cutis, and red eyes (CaPO₄ conjunctivitis).

▶How does acidosis contribute to bone disease in chronic renal failure?

Decreased pH activates the phosphate buffer system, mobilizing phosphate (and calcium) from bone.

▶Why do GI erosions bleed easily in chronic renal failure?

Increased gastrin → ↑HCl causes erosions/ulcers, which bleed readily because of the coexisting thrombocytopathy.

▶What is calciphylaxis in chronic renal failure?

Soft-tissue calcification from CaPO₄ deposition, a consequence of renal osteodystrophy.

▶Why does edema worsen in chronic renal failure GI involvement?

Na⁺/water retention combined with albumin deficiency worsens edema.

▶What neuromuscular features occur in chronic renal failure?

Increased reflexes (irritability) with spasms, tremor, and restless legs, plus hypocalcemia signs (Chvostek, Trousseau).