Chemical pathology of renal disease Flashcards
What kidneys are affect early in AKI and late in CKD?
Excretion and homeostasis
- waste products of metabolism
- fluid and electrolyte balance
- acid-base balance
- removal of drugs and toxins
What kidneys functions are not normally disturbed by AKI?
endocrine functions but in the later stages of CKD they are disrupted
- renin-angiotensin system
- erythropoietin production
- hydroxylation of vitamin D
What is stage 1 AKI?
creatinine rises >26.5 micromol/L in 48 hours OR 1.5-1.9x baseline
urine output - <0.5ml/kg/h for 6-12hours
What is stage 2 AKI?
creatinine rises 2-2.9x baseline
urine output - <0.5ml/kg/h for >12hours
What is stage 3 AKI?
creatinine rises >353.6 micromol/L OR 3x baseline OR need for renal replacement therapy
urine output - <0.3ml/kg/h for >24 hours or anuria for >12 hours
How can the 3 main causes of AKI be divided?
Pre-renal
Renal
Post-renal
What is pre-renal damage?
damage due to underperfusion of an otherwise normal kidney
Therefore as the kidney is normal the metabolic consequences are reduced
Over 1 million nephrons in each kidney which are highly sensitive to toxic and hypoxic injury so underperfusion is very damaging
What are the causes of pre-renal AKI?
hypovolemia - due to hemorrhage or dehydration
sepsis and vasodilation
renal artery stenosis and atherosclerosis
pump failure
What is intrinsic renal damage and what are the causes?
Damage can be of the tubules or the glomerulus
- ischemia
- nephrotoxicity from drugs, poisons, myoglobin, and paraproteins (myeloma)
- pyelonephritis - direct infection of the kidney itself
- trauma
- early stage CKD - glomerulonephritis and interstitial nephritis
What are involved in post renal damage?
post-renal obstruction
- kidney stones
- tumour
- prostatic hypertrophy
What are the key biochemical findings for an AKI caused by pre-renal damage?
urine volume: low urine:plasma osmolality: >2:1 urine [Na]: <15 Plasma Na: high Elevation of urea vs creatinine: urea>>creatinine
What are the key biochemical findings for an AKI caused by intrinsic renal damage?
urine volume: initially high urine:plasma osmolality: <1:1 urine [Na]: >40 Plasma Na: low Elevation of urea vs creatinine: urea=creatinine
What is the treatment for pre-renal damage AKI?
Give fluid to increase renal perfusion
whereas if you did this in intrinsic AKI then it would cause fluid overload and can potentially kill the pt
In intrinsic AKI what are some of the key clinical features?
acidosis - occurs as 100mmol/day of acidic waste products of metabolism are retained - becomes life threatening when pH <7
hyperkalaemia - occurs as K isn’t excreted - becomes life threatening when it increases >8mmol/L
As AKI progresses due to lack of treatment what can happen ?
nitrogenous waste builds up and patients experience nausea, malaise and confusion
also begin to retain electrolytes and water due to the reduction in GFR - leads to hyponatraemia as more water is retained than salt
Fluid overload can follow on from this
How is an AKI managed?
first find cause
stop any NSAIDS, ACE inhibitors or angiotensin receptor inhibitors and any other nephrotoxic drugs
correct any life threatening fluid, electrolyte and acid-base abnormalities
pre-renal = renal perfusion needs to be restored
intrinsic = renal function should be supported with dialysis
post-renal=any obstruction should be removed
What is CKD and what are the causes?
gradual, irreversible changes in renal function
causes: hypertension, diabetes, polycystic kidneys, recurrent pyelonephritis and reflux nephropathy, glomerulonephritis, interstitial nephritis and drugs
How is CKD staged?
determined by serum creatinine and GFR
- early disease - GFR is more sensitive as creatinine levels don’t begin to rise until relatively late in the disease
- creatinine levels are used to monitor disease later on
How is eGFR calculated?
using MDRD formula - calculated based on age, sex, plasma creatinine and a correction factor for ethnicity and paeds
What is the albumin/creatinine ratio?
this may replace GFR estimate in the future
A1 <3
A2 3-30
A3 >30
What are the different stages of CKD?
1 - GFR >90ml/min 2- 60-90 3a- 45-60 3b- 30-44 4- 15-30 5-<15
What are the consequences for stages 3-5?
3a - hypertension due to water retention, increased CVD risk
3b - low calcium due to decreased vitamin D
4- anaemia, anorexia, and hyperphosphataemia
5- salt and water retention, acidosis and hyperkalaemia
How are stages 1-3 CKD managed?
monitoring GFR and urinary albumin:creatinine ratio
Also monitoring of bone health and cardiovascular risk
Any causes treated - e.g. diabetic control and anti-hypertensive treatments
What are the more severe biochemical changes that occur in stages 3-4 CKD?
Largely due to reduced GFR
- elevated ACR, elevated cholesterol and triglycerides (increasing cardiovascular risk) and impairment of immune function
Several endocrine changes occur too
How are patients with stages 3-4 CKD managed?
- need to take 1,25-OH vitamin D due to decreased hydroxylation = leads to low calcium and secondary hyperparathyroidism
- increased PTH leads to osteomalacia and osteitis fibrosa due to increased calcium reabsorption
- decreased GFR leads to an increased phosphate level, these form precipitous with calcium which can cause metastatic calcification
- erythropoietin production also drops causing anaemia
What symptoms start to develop in stage 5 CKD?
Uremic symptoms - due to high levels of creatinine and urea
Phosphate and potassium will be high and patient will be acidotic
What are the main areas that specialists focus on when treating patients with CKD at stage 3b +?
correcting endocrine and metabolic abnormalities with hormone replacement (alfacalcidol and EPO), phosphate binders are given to prevent metastatic calcification, diet modified to reduce potassium and fluids monitored
acid base balance corrected with bicarbonates
dialysis (haemo or peritoneal) and kidney transplant are used as renal replacement
When do CKD patients become oliguric?
not until the very late stages
What is the GFR like in glomerular disease and what is the consequence of this?
very little GFR therefore fluid overload and oliguria
What is the water balance like in polycystic kidneys?
in this kidney disease the nephrons remain healthy so there will be an initial osmotic diuresis, causing polyuria
What happens to the water balance in tubular damage to the kidneys?
there is ineffective water absorption causing polyuria
What are the key characteristics of AKI?
rapid onset
hospitalized
risk increased but not caused by multi morbidity
CKD predisposes to AKI
creatinine and urine output used to classify
What are the key characteristics of CKD?
Gradual onset patient in community often caused by multi morbidity AKI contributes to CKD deterioration eGFR and ACR used to classify
What are the features of pre-renal AKI in terms of:
- urea/creatinine
- electrolyte balance and acid base balance
- fluid balance
- endocrine abnormality
?
- urea/creatinine = urea»_space; creatinine
- electrolyte and acid base = hypernatraemia
- fluid balance = hypovolemia
- endocrine abnormality = none
What are the features of renal AKI in terms of:
- urea/creatinine
- electrolyte balance and acid base balance
- fluid balance
- endocrine abnormality
?
- urea/creatinine = urea = creatinine
- fluid balance = hypervoleamia
- electrolytes . acid base = hyperkalaemia, hyponatriaemia, acidosis
- endocrine abnormality = none
What are the features of CKD in terms of:
- urea/creatinine
- electrolyte balance and acid base balance
- fluid balance
- endocrine abnormality
?
- urea/creatinine = urea= creatinine
- electrolyte balance and acid base balance = hyperkalaemia and acidosis
- fluid balance = euvolaemia (until late)
- endocrine abnormality = persistent
What is renal glycosuria?
due to lack of glucose uptake
What are examples of generalised and selective kidney disorders that do not constitute renal failure?
generalized = faconi syndrome selective = cysteinuria (lack of amino acid uptake)
What are the 3 main forms of renal tubular acidosis?
causes acid base and electrolyte balance disturbance
1) type 1 = distal - causes hypochloracaemic hypokalemic acidosis and kidney stones - due to failure to secrete H+ causing acidosis and excess K+ being lost in exchange for Na
Tx = bicarbonate and K
2) type 2 - proximal = leads to alkalosis - due to bicarbonate leak
3) type 4 is hyperkalaemia due to low aldosterone and renin
When can you get high or low urea other than renal problems?
High - protein load and upper GI bleed
low - low protein diet and anorexia
When can you get high or low creatinine other than renal problems?
high - muscle breakdown
low - small muscle mass
