Chem Path Flashcards
What are the three stages of AKI according to KDIGO?
Stage 1: increase in serum creatinine by 1.5-1.9 times reference sCr or by 26 umol/L; <0.5 ml/kg/hr urine output for 6-12 hours
Stage 2: increase in serum creatinine by 2-2.9 times reference sCr; <0.5 ml/kg/hr urine output for 12-24 hrs
Stage 3: increase in serum creatinine by 2-2.9 times reference sCr or 356 mol/l or more; <0.3ml/kg/hr urine output for more than 24 hours OR anuric for more than 12hrs
Name and describe the two mechanisms that maintain renal blood flow despite changes in systemic blood pressure.
Myogenic Stretch: stretching of afferent arteriol due to high pressure –> constriction to reduce transmission of that pressure to the glomerulus
Tubuloglomerular Feedback: high chloride concentration in the early distal tubule (suggestive of high GFR) –> basolateral adrenaline release from macula dense cells => constriction of the afferent arteriole stimulated which lowers GFR and, hence, chloride concentration
List some drugs that affect renal blood flow.
ACE inhibitors + ARBs – reduce efferent arteriolar constriction
NSAIDs + Calcineurin inhibitors – decreased afferent arteriolar dilation
Diuretics – affect tubular function and decrease preload
List the causes of Pre-Renal AKI
1) True hypovolaemia (eg haemorrhage, vomiting, not taking enough fluids in, DI or DM)
2) ‘pseudohypovolaemia’ (oedema)
3) hypotension
4) selective renal ischaemia (RAS/drugs affecting renal blood flow)
Difference between acute tubular necrosis and AKI
AKI: no structural renal damage, responds immediately to restoration of circulating volume. PROLONGED AKI INSULT -> ATN! (which doesn’t respond well to restoration of circulating volume)
How can you distinguish between ATN and AKI on urine microscopy?
Red cell casts seen in ATN, not AKI
Causes of post-renal AKI
Urinary outflow obstruction:
- prostatic/urethral obstruction
- retroperitoneal fibrosis aka Ormand’s disease
- Bilateral ureteric obstruction
- Blocked urinary catheter
Prolonged urinary outflow obstruction leads to…
Glomerular ischaemia
tubular damage
long-term interstitial scarring
List the possible sites of disease in intrinsic AKI.
Anywhere along nephron!
- Vascular (e.g. vasculitis)
- Glomerular (e.g. glomerulonephritis)
- Tubular (e.g. ATN)
- Interstitial (eg analgesic nephropathy, due to long-term use of analgesics)
What are the mechanisms that can cause intrinsic renal AKI?
- direct tubular injury due to ischemia/toxins ( NB: ischaemia > toxins. Toxins can be endogenous (eg myoglobin in rhabdomyolysis or immunoglobulins in myeloma) or exogenous (eg CONTRAST MEDIUM> aminoglycosides, amphoteracin, acyclovir)
- Immune dysfunction -> renal inflammation (relatively common)
eg glomerulonephritis, vasculitis - infiltration/abnormal protein deposition (eg amyloidosis (-> nephrOtic syndrome), lymphoma, multiple myeloma)
5 causes of CKD (+ which two are most common?)
DIABETES HYPERTENSION (-> atherosclerotic renal artery disease/RAS) chronic glomerulonephritis infective/obstructive uropathy polycystic kidney disease
Outline the consequences of CKD
Progressive failure of homeostatic function (acidosis, hyperkalaemia) Progressive failure of hormonal function (anaemia, renal bone disease) Cardiovascular disease (vascular calcification, uraemic cardiomyopathy) Uraemia and death
What are the consequences of renal acidosis? + what is the treatment for it?
Muscle and protein degradation
Osteopaenia due to mobilisation of bone calcium Cardiac dysfunction
Oral sodium bicarb
What is the most common consequence of CKD? + what does this impact??
Hyperkalaemia. Impacts heart and muscle function.
Name 2 classes of drug that can cause hyperkalaemia
ACEi
K+ sparing diuretics (eg spironolactone)
What type of anaemia does chronic renal disease cause?
Normocytic, normochromic
How is anaemia of chronic renal disease treated?
Artificial erythropoiesis-stimulating agents:
Erythropoietin alfa (Eprex)
Erythropoietin beta (NeoRecormon)
Darbopoietin (Aranesp)
NOTE: if CKD is not responding to erythropoiesis stimulating agents, consider iron deficiency, malignancy, B12 deficiency, TB, hyperparathyroidism.
List some types of renal bone disease.
Osteititis fibrosa cystica
Osteomalacia
Adynamic bone disease
Mixed osteodystrophy
Outline the pathophysiology of renal bone disease.
Damaged kidneys are unable to excrete phosphate and activate vitamin D
Phosphate retention stimulates the production of FGF23 and Klotho
This lowers the levels of activated vitamin D
To try and get rid of the excess phosphate, the body will produce more PTH
Furthermore, to try and increase levels of vitamin D, the body will produce more PTH (i.e. there are two stimuli for PTH release)
High levels of phosphate in the blood will complex with calcium leading to a reduction in the level of free calcium High levels of PTH will result in the bone becoming resistant to PTH
What is osteitis fibrosa cystica?
Caused by osteoclastic resorption of calcified bone and replacement by fibrous tissue (feature of hyperparathyroidism)
What is adynamic bone disease?
Overtreatment leading to excessive suppression of PTH result in low bone turnover and reduced osteoid
Outline the treatment of renal bone disease.
Phosphate control – dietary, phosphate binders
Vitamin D activators – 1-alpha calcidol, paricalcitol
Direct PTH suppression – cinacalcet (works by increasing the sensitivity of the calcium sensing receptor)
Which 3 consequences of CKD are most likely to kill a patient?
Cardiovascular disease
Hyperkalaemia
Acidosis
What are the indications for dialysis?
Acidosis (<7.1) Electrolyte imbalance (K+, refractory to Tx >6.5mEq/L) Intoxication* Oedema Uraemia
*Which drugs/toxins are dialysable?
Salicyclates Theophylline Uraemia Methanol Barbituates Lithium Ethylene glycol Dabigatran
