Chemical Pathology Of Renal Disease Flashcards
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What are the homeostasis functions of the kidneys?
Waste products of metabolism
Fluid/electrolyte balance
Acid-base balance
Removal of drugs and toxins
What are the endocrine functions of kidney?
RAAS
Erythropoietin production
Hydroxylation of vitamin D
Which functions of the kidneys are effected by AKI and CKD?
AKI= excretion and homeostasis in early AKI
CKD= endocrine and then excretion later in CKD
How are the different stages of AKI defined? Which stages is associated with increased in-hospital mortality?
Stage 1:
Serum creatinine: >=26.5 micro mol/L in 48 hrs or 1.5-1.9 x baseline
Urine output: <0.5ml/kg/h for 6-12 hours
Stage 2:
Serum creatinine: 2.0-2.9 x baseline
Urine output: <0.5ml/kg/h for >12 hrs
Stage 3:
Serum creatinine: >=3 x baseline or rise in >=353.g micromols/L or need for renal replacement therapy regardless of creatinine levels
Urine output: <0.3ml/kg/h for >24hrs
Stage 2
What are the causes of AKI?
Renal underperfusion
Intrinsic renal damage
Obstruction
What is the most common cause of AKI in hospitalised patients and why is this?
Renal underperfusion
Due to causes being associated with hosptial setting:
Hypovolaemia (trauma/GI bleed)
Sepsis (afferent arteriole vasodilation)
Renal artery stenosis/atherosclerosis
Pump failure (HF)
Why does intrinsic renal damage occur?
Ischaemia
Nephrotoxins
Infection (pyelonephritis
Trauma
Early stage inflammation causes of CKD (glomerulonephritis)
When is post-obstructive diuresis occur and what are the potential problems?
When catheter inserted to relieve retained urine in renal obstruction
Can then cause pre-renal injury due to fluid depletion associated with the diuresis= need to ensure fluids being replaced
What are the stages involved in AKI development?
Pre-renal cause (hypovolaemia/sepsis/renal artery stenosis) leads to renal underoperfusion
Pre-renal renal failure leads to prolonged renal underperfusion which can cause acute tubular necrosis
Acute tubular necrosis can lead to intrinsic renal failure
What are the precipitating factors of glomerular damage leading to intrinsic renal failure?
Trauma
Toxins
Infection
Infarction
Inflammation
What are the most common causes of AKI in patients?
Hypovolaemia and sepsis
How can you differentiate between a pre-renal renal failure and intrinsic renal AKI?
Pre-renal Low urine vol Urine:plasma osmolality= high i.e. trying to preserve water (concentrated urine) Urine sodium conc= low Plasma sodium= high Serum elevation of urea >> creatinine
Intrinsic
Initially high= due to kidney being unable to reabsorbed water and electrolytes
Urine:plasma osmolality= low or similar
Urine sodium conc= high
Plasma sodium= low
Serum elevation urea=creatinine
What is the most specific test for differentiating between pre-renal and intrinsic renal AKI? What would the results be and why?
Urine sodium concentration
Pre-renal= LOW
Aldosterone being released to retain sodium
Intrinsic damage= HIGH
Kidney unable to reabsorb sodium
How does the treatment of pre-renal AKI differ from intrinsic renal damage? Why is this?
Pre-renal= fluid cures
Due to low fluid volume being the reason for underperfusion
Intrinsic= fluid kills
Kidney unable to clear the fluid which lead to fluid overload
What are the biochemical features of intrinsic AKI?
Retain acidic waste products= acidosis
Retain Potassium
Retain nitrogenous waste products
I.e. leads to uraemic symptoms= nausea, malaise, confusion
Retain salt and water = decreased GFR
What serum concentration of potassium is life-threatening?
> 8mmol/L
How would someone with intrinsic AKI present?
Hyperkalaemia metabolic acidosis
Malaise + nausea
Hyponatraemia due to fluid retention
Fluid overload
How is AKI managed?
Determine whether pre-renal, intrinsic or post-renal causes
Identify underlying cause
Stop ACEi/ARBs/NSAIDs
Correct life-threading fluid and electrolytes and acid base abnormalities
Restore renal perfusion if pre-renal
Haemofiltration or dialysis to support renal function in life threatening AKI
When is restoration of renal perfusion in pre-renal AKI contraindicated and why?
Heart failure
Leads to fluid overload
What is CDK and what are the main causes?
Gradual irreversible change in kidney function
DM Hypertension Polycystic kidney disease Recurrent pyelonephritis Glomerulonephritis Interstitial nephritis Multisystem disease Drugs
How is CDK monitored?
24 hr urine collection for protein to determine GFR
Estimated GFR
Creatine (in end stage)
Albumin/creatine ratio
Why is GFR used in early stages of CDK and creatine used in late stages?
Can loose 50% of kidney function before creatinine changes
EGFR changes less in later stages whereas creatinine changes a lot
How is eGFR used to stage CKD?
>90= stage 1 60-90= stage 2 45-60= stage 3a 30-44= stage 3b 15-30= stage 4 <15= stage 5
NOTE= the 1st number of the range values is half of the upper value in previous stage range after stage 1 i.e. 90/2= 45
At what stage of CKD does a patient present with clinical consequences? Which clinical signs are associated with the stages?
3a= hypertension and increase CVD risk 3b= low calcium and secondary increase PTH (due to problems with vitamin D hydroxylation) 4= anaemia(due to erythropoietin prod)/anorexia/high phosphate 5= salt and water retention/acidosis/high potassium
What are the biochemical changes associated with CKD stage 3-4?
Elevate creatine
Reduced eGFR
Elevated ACR
Reduced 1-alpha hydroxylation of vitamin D = decreased amount of active vitamin D present
Reduced erythropoietin production (renal anaemia)
Elevated lipids and triglyceride (increased CVD risk)
Impaired immune function
Why are hypocalcaemia and secondary hyperparathyroidism associated with stage 3-4 CKD?
Decreased 1-alpha hydroxylation of vitamin D leads to impaired calcium absorption in GIT= hypocalcaemia
Hypocalcaemia detected by parathyroid gland which stimulates increased production of PTH to promote increase osteoclast function to increase bone resorption to release calcium
What are the biochemical changes associated with stage 4-5 CKD?
Elevate creatinine and urea= leads to uraemic symptoms
High phosphate
Acidosis
Hyperkalaemia= only presents in later stages due to increased gut-losses offsetting it until that point
How does the site of kidney damage influence the water balance in CKD?
Glomerular damage:
Little glomerular filtrate= little urine produce (oliguria) i.e. fluid overload
Healthy nephron in disease kidney
Tubules unable to reabsorb electrolytes or water i.e. osmotic diuresis + polyuria
Tubular damage
Ineffective water reabsoprtion i.e. polyuria
Is a CKD patient more likely to present with polyuria or oliguria?
Polyuria
Oliguria only present in later stages of CKD
What are the 2 possible mechanism contributing to renal bone disease?
- Decreased 1-alpha hydroxylation= decreased plasma calcium and increased PTH
- Decreased GFR
- increased plasma phosphate= increase calcium/phosphate products
- metabolic acidosis= dissolves bone buffers
What bone diseases are associated with CKD and why?
Osteomalacia = decreased plasma calcium
Osteitis fibrosa = increased bone resorption
Metastatic calcification= increase calcium/phosphate products
Osteoporosis= bone decay due to dissolved bone buffers
How is CKD stage 2-3a managed?
Monitor patients via eGFR + ACR/ BP + lipids/ bone profile + PTH in stage 3a
Treat causes (diabetes, hypertension, recurrent UTI)
Avoid precipitates of AKI
Block slow progression by blocking RAAS if ACR via ACEi/ARB
How is stage 3b-5 CKD managed?
Endocrine abnormalities:
Alfacalcidol= corrects calcium and prevens tertiary hyperparathyroidism
Erythropoietin
Phosphate binders= decreases risk of metastatic calcification
Modified diet to decreased potassium
Fluids
Bicarbonate to correct acid-base disturbances
Renal replacement therapy i.e. haemodialysis or peritoneal dialysis
What is tertiary hyperparathyroidism?
Excessive production of PTH due to long-standing secondary hyperparathyroidism
What are the different causes of renal tubular disorders?
Specific transport defects i.e. glucose/amino acids/phosphates
Global tubular defect i.e. fanconi syndrome
Renal tubular acidosis i.e. causes acid/base and electrolytes disturbances
