147 - Pathophysiology of Acute & Chronic Renal Failure Flashcards
Definition of acute renal failure
Urine flow less than 500 ml/day
Common time-course for chronic renal failure to develop
6 months or more
Normal GFR
125mL/min, 180L/day
GFR of significant chronic renal failure
Under 50mL/minute, under 72L/day
Reversibility of acute and chronic renal failure
Acute is often reversible.
Chronic is irreversible
Hallmark of chronic renal failure
Creatinine excretion and a decrease in CFR from a loss of functional nephrons
Broad types of nephron pathology
Glomerular and tubular. Often a mixed pathology.
Examples of renal endocrine impairment
1
2
3
1) Ras (renin-angiotensin system) (excessive activation)
2) Vitamin D activation
3) Epo
Ras endocrine pathologies
Excessive activation (but rarely): vasoconstriction can impair RBF; possibility of “malignant hypertension”
Most important endocrine dysfunction in CRF
Vitamin D activation.
Leads to a unique pattern of bone disease.
Effects of vitamin D activation in CRF
Osteo-dystrophy, renal rickets; exacerbated by hypocalcaemia
Effects of epo dysregulation with CRF
CRF seems to be invariably associated with anaemia
Effectiveness of urea in assessing GFR
Poor
Proportion of urea that is reabsorbed
~50%
What can alter urea in urine without affecting kidneys
Diet. Urea is produced from protein
States where urea can be elevated
CRF, catabolic states, steroid use, cachexia in cancer
What suppresses urea excretion?
Malnutrition, liver disease
Features of creatinine in GFR assessment 1 2 3 4 5
1 Creatinine production is constant
2 Filtered, but 15% bound to plasma proteins (underestimates GFR)
3 Not reabsorbed
4 Small amount of secretion (overestimates GFR)
5 (2) and (4) tend to cancel out
Normal serum creatinine level
50-120 μM/L
What is daily production of creatinine proportional to?
Muscle mass
What is equal to creatinine filtration?
Creatinine excretion
What is equal to creatinine clearance?
GFR
Aspects of creatinine that can skew calculation of GFR from creatinine excretion
1
2
15% of creatinine is bound to plasma proteins.
Therefore can underestimate GFR>
Some secretion of creatinine occurs. This can overestimate GFR.
These two roughly cancel out.
Equation for creatinine clearance
UV/P
U = urinary concentration of creatinine V = Urine volume/day P = Plasma concentration of creatinine
Because UV is often constant, can say that creatinine clearance is inversely proportional to creatinine plasma concentration
What must you do for plasma creatinine concentrations to be meaningful?
Take more than one. People can have normally high creatinine. As creatinine levels should be constant, look for increases in concentration.
Net filtration pressure
10mmHg from glomerulus into Bowman’s capsule
Features of acute renal failure 1 2 3 4
- Oliguria
- Anuria (rarely)
- GFR falls acutely (hours to days)
- Easily missed (depending on cause) because of itself may be asymptomatic
Types of acute renal failure
Pre-renal
Renal
Post-renal
Most common cause of acute renal failure
Pre-renal.
EG: shock, dehydration.
Pre-renal acute renal failure
Anything that drops blood pressure to the point where no filtration occurs across glomerulus and Bowman’s capsule
Systemic perfusion pressure at which ARF occurs
Under 70mmHg
Glomerular hydrostatic pressure at which ARF occurs
Under 45mmHg
Examples of causes of pre-renal ARF 1 2 3 4 5
– Shock – Sepsis – Haemolysis – Rhabdomyolysis – Nephrotoxic drugs (actually cause tubulo-interstitial nephritis, a renal cause)
Examples of things that can cause intrinsic renal ARF 1 2 3 4
•Glomerular disease
•Interstitial nephritis (Tubulo-interstitial)
–Inflammatory reaction, often drug-related
•Tubular damage
–ischemia
•Acute tubular necrosis, vascular obstruction
•toxins
-antibiotics, X-ray contrast media, myoglobin
ATN
Acute tubular necrosis.
So common as to be almost synonymous with ARF.
Most common renal cause of ARF
Acute tubular necrosis
Things that can cause acute tubular necrosis
Ischaemia, toxins
Effects of acute tubular necrosis 1 2 3 4
•oliguria (
Main concern with CRF
Accumulation of toxic metabolites, EG creatinine.
Loss of hormonal function of kidneys (EG: vitamin D, epo, renin)
Main concern with ARF
Accumulation of H+ and K+ ions. Leads to acidosis and hyperkalaemia.
Treatment of ARF
Rehydration.
Post-renal ARF
•Outlet Obstruction
–Ureteric, cystic or urethral
–stones, clots, fibrosis, tumors
Treatment of post-renal ARF
Not just rehydration. Also need to remove the obstruction.
Features of chronic renal failure 1 2 3 4 5
- Irreversible loss of renal function
- Reduction in functional renal mass
- Develops over months to years (highly variable rates of decline)
- Aka “uraemia”
- Leads to End-Stage Renal Disease (ESRD)
Effect of CRF on glomeruli
1
2 a, b, c
•Remaining nephrons hypertrophy •Glomerular hyperfiltration –loss of functional reserve –glomerular hypertension –further damage and glomerulosclerosis
Uremia
1
2
3 a, b, c
•Accumulation of “uremic” toxins •Mostly urea, but not exclusively •Symptomatic with under 30% of renal function –Fatigue –Loss of appetite –Skin pigmentation (lemon)
Main causes of CRF 1 2 3 4
1) Diabetes
2) Hypertension
3) Chronic glomerulonephritis
4) Polycystic kidney disease
Salt and water imbalances in CRF
1
2
•Predominantly glomerular disease –Sodium retention and hypertension •Predominantly tubular disease –Sodium wasting and low BP –Impaired concentrating ability & polyuria
Potassium in CRF
–Tends to rise, especially late-stage
–Higher in diabetes
–If rapidly rises, can lead to arrhythmia
pH in CRF 1 2 3 4 5
–Falls i.e. H+ accumulates; failure to excrete non-volatile acids
•Produced at high rate in normal metabolism
•Excretion requires high GFR
•Reduced ammonia production
•Low [HCO3-]
Calcium and phosphate in CRF
1
2
3
- Reduced phosphate excretion
- Still reabsorbs same amount of phosphate, while secretion is decreased
- Leads to rise in [PO4] (should be 1 - 1.3 milimols)
- Reciprocal reduction in [Ca]
Part of nephron that transports phosphate
Epithelial pump in proximal tubule.
Clears ~1 milimol/day
Effect of elevated phosphate in CRF
Calcium phosphate can begin precipitating (EG on bones)
Effect of CRF on vitamin D3
–Reduced renal mass and Vit D activation
–Hyperphosphatemia
–Renal “rickets”: osteomalacia with fractures and subperiosteal resorption
Hormonal effect of high phosphate
High parathyroid hormone release.
Leads to excessive osteoclastic activity.
Osteomalacia
Similar to osteoporosis.
If there is low serum Ca2+, then body starts taking Ca2+ from bones.
Renal osteodystrophy
Combination of low serum Ca2+, leading to body taking Ca2+ from bones. Also increased PTH leads to excessive osteoclast activity
