Biochemistry of Renal Failure Flashcards
Functions of the Kidney →
Excretion/Homeostasis
Endocrine functions
Excretion/Homeostasis
- Waste products of metabolism
- Fluid/electrolyte balance
- Acid-base balance
- Removal of drugs and toxins
Endocrine functions
- Renin Angiotensin Aldosterone system
- Erythropoietin production
- Hydroxylation of Vitamin D
Inadequate renal blood flow
the same blood supply supplies pressure and oxygenation of the tubules and therefore important to address quickly.
Acute Kidney Injury →Definition
Any physical, chemical toxic, or ischaemic insult causing rise in creatinine OR fall in urine output over timescale of hours to days (don’t need both).
Acute Kidney Injury → Epi
- Common – 8% (of all creatinine measurements) – fit the criteria above
- Often missed – 40% of those developing after submission
- Doubles length of stay (stage 1,2,3)
- Increases mortality – 2,4,6x @ 1 year in stage 1,2,3
Stage 1
Serum creatinine (SCr) criteria
Urine output criteria
Increase >26 umol/L within 48 hrs or
Increase >1.5 to 1.9 X reference SCr
6 consecutive hrs
Stage 2
Serum creatinine (SCr) criteria
Urine output criteria
Increase >2 to 2.9 X reference SCr 12 hrs
Stage 3
Serum creatinine (SCr) criteria
Urine output criteria
Increase >3 X reference SCr or increase >354 umol/L or commenced on renal replacement therapy (RRT) irrespective of stage 24 hrs or anuria for 12 hrs
Aetiology of AKI → Pre-Renal (most common)
Hypovolemia
• Haemorrhage
• Sepsis
Pump Failure
Aetiology of AKI → Renal (tubular damage)
Ischaemia – not correcting pre-renal Nephrotoxins • Drugs, poisons, metals, myoglobin* (monomeric protein carrying oxygen in tisssues), paraproteins Glomerulonephritis Interstitial nephritis
Aetiology of AKI → Post-Renal
Stones
Tumour
Prostate
• Myoglobin significance
can filter as its smaller. If too excessive can crystallise from reduced urinary output i.e. during haemorrhage. Following major trauma there is lots o f myoglobin release and so important to think of in these patients.
Biochemical vs. clinical features: of AKI
- Biochemical changes occur early but are eventually life-threatening (High K+, acidosis)
- Clinical features are non-specific and occur late
Biochemical vs. clinical features: of AKI
Due to:
• Failure to remove
o Nitrogenous waste products
o Fluid, electrolytes
o Acids
Biochemical vs. clinical features: of AKI Outcome:
• Retain nitrogenous waste products
o Nausea; malaise; confusion
• Reduced GFR → fluid overload
• Retain acidic waste products of metabolism
o 100 mmol/day from metabolism
o Life threatening once plasma pH >7.0 ([H+] = 10-7)
• Retain Potassium
o Life threatening once [K+] >8mmol/L
• Don’t see endocine problems in AKI – not enough time to cause morbidity
Disproportionate increase of urea compared to creatinine 2 reasons
Urea rise explanation 1:
• Urea and creatinine are both markers of Renal function as both freely filtered at glomerulus. Degree of clearance reflects kidney function.
• Creatinine – freely filtered but no reabsorption
• Urea is filtered by glomerulus and reabsorbed at PT.
• The lower renal blood flow the lower the GFR the more opportunity there is for Urea to be reabsorbed,
• Low renal blood flow lower UO and more urea reabsorption so Urea is higher than creatinine
Urea rise explanation 2:
Hematemesis (Upper GI bleed) production of creatinine is proportional to muscle mas, Urea proportional to diet protein (hepatic function influential). ‘Large protein meal’ because of bleed and therefore will increase urea regardless of renal function.
Treatment of acute renal Failure →
Correct life threatening abnormalities → Fluid (for renal perfusion_ • Maintain fluids • Replace fluids • Resuscitate fluids → Electrolyte → Acid/base Restore renal perfusion if possible Support renal function if not → Dialysis/hemo-filtration – restoring function
High and Low urea caused by
High:
Protein load
Dehydration
Low:
Low protein diet
Anorexia
High and low creatinine caused by
High:
Muscle breakdown
Low:
Small muscle mass
Who is at risk of AKI
75+; Hypertension; CKD; Diabetes; Chronic Liver Disease; CCF; Myeloma; Sepsis; Drugs (what has changed)
Causes of CKD
o Diabetes Mellitus (most common because better survival), Hypertension
o Polycystic Kidney Disease
o Glomerulonephritis, Pyelonephritis, Interstitial nephritis
o Multisystem disease
o Drugs
Serum Creatinine and GFR: (why creatinine isn’t used really)
- Need to loose the equivalent of half the renal function before the Serum creatinine rises significantly.
- Low muscle mass (elderly) curve shift downwards and therefore lost 1 2/3 of renal function before the creatinine is above the normal range.
Biochemical changes in CKD
• Elevated Urea/Creatinine
• Acidosis (dissolving buffers primarily form bone – backfires on bone health)
• Hyperkalaemia – offset by increased gut losses
• High phosphate (main cause of morbidity)
• Low calcium – causes secondary hyperparathyroidism
• Endocrine changes
o Reduced 1α hydroxylation of Vitamin D -
o Reduced Erythropoietin, causing anaemia
• Lipids
o Elevated Cholesterol and Triglyceride, accounts for increased risk of CHD
• Impaired immune function
Water balance in renal disease:
glomerular damage
Little glomerular filtrate
Oliguria
Water balance in renal disease Healthy nephron in diseased kidney
Osmotic diuresis
Polyuria
Water balance in renal disease Tubular damage
Ineffective water reabsorption
Polyuria
Mechanisms of renal bone disease:
Disease of Hydroxylation Process →
- Decreased 1α hydroxylation
- Decreased 1,25 Vit D
- Decreased gut absorption of Ca++
- Reduced plasma Ca++
- Increased PTH – increased bone resorption
Decreased Plasma Ca ++
Osteomalacia
Increased PTH (drop in plasma calcium)
Increased Bone resorption
Osteitis fibrosa
Increased Calcium/ Phosphate product
Metastatic Calcification
Dissolved bone buffers from metabolic acidosis
Bone decay
Osteoporosis
Treatment: of metabolic renal disease
- Active Vitamin with the aim of keeping PTH in the normal range= confirmation that process is in homeostatic balance.
- Phosphate binders – keeps phosphate down
- Bicarb – to mitigate the acidosis
Renal Tubular Disorders:
Transport Defects • Glucose (exceed threshold (capacity) for reabsorption) o Renal Glycosuria o Pregnancy – increased filtration rate • Amino acid o Selective e.g. Cystinuria o Generalized • Phosphate o Hypophosphataemic rickets Globular tubular defect – Fanconi Syndrome – multiple defects across multiple transporters.
Renal Tubular Acidosis: Type 1 (Distal)
Failure to excrete H+ → acidosis
Excess K+ loss in exchange for NA → low K+
Can’t acidify urine
Renal Tubular Acidosis:Treatment of Type 1
Bicarbonate and K+
Renal Tubular Acidosis: Type II (Proximal)
Bicarbonate ‘leak’ – no plug in bath
Renal Tubular Acidosis: Treatment of Type II
Bicarbonate
Renal Tubular Acidosis: Type IV
Description: (low renin, low aldosterone)
Both H+ and K+ excretion from DCT defective
Often asymptomatic, sometime high K+
