55. Functional manifestations of renal disorders – edemas, hypertension, anemia, renal osteodystrophy, hemostatic disturbances, polyserositis, disturbances in acid-base and water- electrolyte balance. Uremia and uremic encephalopathy.

Functional manifestations of chronic renal failure

1) Hypertension

1. a) Chronic hypoperfusion → renovascular hypertension → high renin
2. b) Nephrectomy → renoprival hypertension → low renin

2) Edema

1. a) Nephritic (decreased permeability)

• Primary Na+ retention (primary hypervolemic)
• ⬇ sympathetic tone
• ⬇ RAAS
• Secondary Na+ retention (membranogenous)

1. b) Nephrotic (increased permeability)

• ⬇ Oncotic pressure
• ⬆ RAAS
• ⬆ Sympathetic tone

3) Osteodystrophy

• Renal osteodystrophy (ROD), also known as uremic osteopathy, is a constellation of musculoskeletal abnormalities that occur in patients with chronic renal failure
• GFR → Phosphate retention → Ca2+ → Secondary PTH → Osteoclast activity → Osteopenia demineralisation → Osteodystrophy
• GFR → 1,25 Vit D3 → ( Ca2+...) and ( Osteoclast activity…) → Osteodystrophy
• GFR → metabolic acidosis (retention) → Osteodystrophy

4) Altered diuresis

1. a) Increased (polyuria) = > 2 L/ 24 hr

• Tubular dysfunction → dehydration (hypovolemia)

1. b) Normal (normouria) = 0.5 - 2.0 L/ 24 hr
2. c) Decreased (oliguria) = < 0.5 L/ 24 hr OR Absent (anuria) = < 0.15 L/ 24 hr

• Glomerular hypo- and afunction → hyperhydration (hypervolemia)

5) Proteinuria and hematuria

1. a) Proteinuria

• Increased permeability of glomerular basal membrane → overwhelmed (up to 1 g/ 24 hr) or suppressed tubular reabsorption → proteinuria → cylindruria (presence of casts in urine)
• Mild proteinuria = 0.15 - 0.5 g/ 24hrs
• Moderate proteinuria = 0.5 - 3.5 g/ 24hrs
• Severe proteinuria = > 3.5 g/ 24hrs
• Albuminuria is more specific for glomerular diseases than proteinuria

1. b) Hematuria

• Increased permeability of glomerular basal membrane → microhematuria (>3 Ers)
• Altered shape in renal hematuria

6) Anemia

• Decreased erythropoietin production → decreased stimulation of erythropoiesis → normochromic and normocytic anemia
• Decreased transferrin and other proteins → iron-deficient anemia
• Toxin damage → hemolytic anemia + hematuria

7) Lithogenesis

8) Hypercoagulability

• Loss of antithrombin III, urokinase, fibrinogen

9) Hypocoagulability

• Accumulated toxins impede glycoproteins on surface of platelets causing thrombocytopenia

10) Uremia

• Increased levels of urea and uric acid in the blood due to kidneys reduced clearance ability
• Fatigue, headache, pruritus (urate crystals in the skin → itching)
• Polyserositis (pericarditis, peritonitis, pleuritis)
• Uremic encephalopathy
• Accumulation of toxins that cross BBB
• Active excitatory NMDA
• Inhibit GABA receptors
• Deposition of Ca2+ in cortex → neurotoxicity

11) Metabolic acidosis

• Increased K+ and phosphate
• Decreased Ca2+ and Na+
• Metabolic acidosis caused by accumulation of H+ ions due to decreased excretion
• Compensated by respiratory alkalosis