Question 19

Describe the changes that occur in the plasma with renal dysfunction.

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College Answer

A good answer required an integrated knowledge of various aspects of basic physiology. 
Most often there was a lack of breadth and/or depth of knowledge (e.g. mention that 
plasma creatinine increases, but failure to mention that it only increases after substantial 
(>75%) loss of nephron function). It was expected that some mention of changes in 
electrolytes (e.g.Na+, K+, Ca2+), HCO3, PO4, hormones (1, 25 vitamin D, erythropoietin), 
proteins, etc. be included.


  • Volume changes
    • There is less capacity to reabsorb water 
      • In polyuric phase of ATN, this produces an uncontrolled diuresis
    • Glomerular filtration decreases with chronic renal damage
      • In chronic renal failure, this results in decreased capacity to eliminate water  ("fluid overload")
    • Renal responsiveness to vasopressin and aldosterone decreases
      • The ability to regulate body fluid volume and osmolality is decreased or absent
  • Electrolyte changes
    • Hyponatremia can develop as the result of impaired water elimination
    • Hyperkalemia can develop (not enough distal tubular secretion)
    • Hyperphosphataemia develops due to the failure to eliminate phosphate
    • Hypocalcemia can develop initially in response to this
    • Hypercalcemia can develop as a compensatory phenomenon (secondary and tertiary hyperparathyroidism)
  • Osmotically active solutes
    • Urea increases, as its clearance is decreased (decreased GFR and fewer nephrons overall)
    • Organic acids and various waste polypeptides are retained because their active secretion mechanisms have failed
  • Oncotically active solutes
    • ​​​​​​​Renal failure can be associated with nephrotic syndrome, which results in the loss of oncotically active protein from the blood stream
  • Changes in blood pH
    • Bicarbonate reabsorption capacity becomes less flexible
      • Thus, no further renal compensation for respiratory acid-base disturbances is possible
    • Renal acidification mechanisms are impaired, and thus:
      • Renal compensation for metabolic acidosis (by increased ammonium excretion) is impaired
      • Renal elimination of titratable acids is decreased
    • The net results of this are:
      • A normal anion gap metabolic acidosis (due to the failure of renal acidification mechanisms)
      • A high anion gap metabolic acidosis (due to accumulation of non-volatile acids) 
  • Changes associated with renal endocrine function
    • Anaemia due to decreased erythropoietin synthesis
    • Hypocalcemia due to decreased calcitriol (Vitamin D) conversion
    • Thrombocytopenia due to decreased thrombopoietin synthesis
    • Indirect neuroendocrine changes resulting from renal failure include:
      • Renin release, due to decreased renal salt delivery, with the resulting activation of RAAS and increased fluid retention/hypertension
      • The RAAS is thought to play a pathophysiologic role in the progression of chronic renal failure


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Szamosfalvi, Balazs, and Jerry Yee. "Considerations in the critically ill ESRD patient." Advances in chronic kidney disease 20.1 (2013): 102-109.

Arulkumaran, N., N. M. P. Annear, and M. Singer. "Patients with end-stage renal disease admitted to the intensive care unit: systematic review." British journal of anaesthesia 110.1 (2013): 13-20.

Thompson, Stephanie, and Neesh Pannu. "Renal replacement therapy in the end-stage renal disease patient with critical illness." Blood purification 34.2 (2012): 132-137.

Wills, M. R. "Biochemical consequences of chronic renal failure: a review." Journal of clinical pathology 21.5 (1968): 541.