7.1b Chronic Kidney Disease (CKD) Pathophysiology - video 1

Overview

• Chronic Kidney Failure: Also known as chronic kidney disease (CKD), it is the end-stage of kidney disease where there is an irreversible loss of nephrons (functional units of kidneys) leading to a toxic state such as uremia.

Anatomy Recap

• Kidneys connect the ureter to the bladder, which stores urine.
• Vascular connections: Inferior Vena Cava and Descending Aorta.

Causes of Chronic Kidney Failure

• Acute Kidney Injury (AKI)
  • Reversible; if unchecked, can lead to chronic failure.
  • Causes categorized as:
    - Pre-renal: Renal artery stenosis, heart failure, hemorrhage.
    - Intrarenal: Glomerulonephritis, tubular necrosis, interstitial nephritis.
    - Post-renal: Benign prostatic hyperplasia, renal stones, tumors.
• Hypertension
  • Increases pressure and thickens blood vessels.
  • Reduced blood flow to nephrons, decreasing Glomerular Filtration Rate (GFR).
  • Activates Renin-Angiotensin-Aldosterone System (RAAS).
  • Leads to glomerulosclerosis and nephron loss.
• Diabetes
  • Leads to diabetic nephropathy and chronic kidney failure.
  • Key changes: Mesangial expansion, podocytopathy, basement membrane thickening, sclerosis.
  • High blood glucose causes oxidative stress, leading to nephropathy.
• Other Kidney Diseases: Polycystic kidney disease.

Pathophysiology

• Loss of nephrons causes blood to divert to surviving nephrons, causing hyperfiltration.
• Initial increase in GFR, but eventual sclerosis and nephron loss.
• Late-stage results in decreased GFR, urine output, and waste retention (uremia).

Clinical Manifestations

Sodium and Water Balance

• Increased sodium and water retention leads to hypertension and edema.
• Risk with fluid loss from vomiting/diarrhea.

Potassium Balance

• Decreased GFR causes potassium retention, leading to hyperkalemia.
• Avoid potassium-sparing diuretics and ACE inhibitors.

Metabolic Acidosis

• Diminished ability to excrete hydrogen and generate bicarbonate.
• Leads to acidosis and potential bone decalcification.

Mineral and Osteodystrophy

• Loss of nephron function reduces calcitriol production.
• Results in hypocalcemia and secondary hyperparathyroidism.
• Leads to osteodystrophy due to bone breakdown.
• Leads to hyperphosphatemia due to decreased phosphate excretion.

Uremia

• Due to inadequate excretion of urea.
• Causes neurological symptoms, gastrointestinal issues, reproductive changes, and skin changes.

Late-Stage Manifestations

• Decreased renin production leads to low blood pressure.
• Decreased erythropoietin causes anemia.
• Lower production of calcitriol results in renal osteodystrophy.

Conclusion

• Chronic kidney failure results from various causes leading to irreversible nephron loss and significant systemic effects.