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