Chempath - LFTs, Cardaic Enzymes and Renal Function Flashcards
Marks of liver synthetic function
Clotting (INR)
Albumin
Glucose
However bare in mind that all of these things can go off by issues not directly cased by the liver.
Markers of liver cell damage
Hepatocyte cell damage - ALT, AST
Biliary stasis - ALP, GGT
Bilirubin
Aspartate aminotransferase (AST)
Found in the Liver, cardiac and skeletal muscle, and the kidney and brain.
AST:ALT = 2 is supportive of alcoholic hepatitis - alcohol makes an ASS out of you
Alanine aminotransferase
Found primarily in the
liver, more sensitive than AST for hepatocyte damage.
Raised when hepatocytes die. AST:ALT =1 supportive of viral hepatitis.
Alkaline Phosphatase (ALP)
Found in the liver, bones, placenta.
Raised with cholestasis (either intrahepatic or extrahepatic) and bone disease, ↑++ in pregnancy
CAUSES of raised ALP:
Physiological: Pregnancy (3rd trimester), Childhood (during growth spurt)
Pathological:
- > 5x ULN = Bone (Pagets, osteomalacia), Liver (Cholestasis, Cirrhosis)
- <5x ULN = Bone (tumours, fractures, osteomyelitis), Liver (infiltrative disease, hepatitis)
Gamma GT
Found in hepatocytes and biliary cells, also found in the kidney and pancreas.
Elevated in chronic alcohol use
Also bile duct disease and metastases. Used to confirm hepatic source of ↑ALP
Alpha fetoprotein
Tumour marker. Also raised in hepatic damage/regeneration, pregnancy & testicular ca.
Albumin
Average adult synthesises 200mg/kg of albumin per day
Important serum protein which binds many hormones, calcium and other metabolites.
Hypoalbuminaemia is common in hospital patients as acute illness/systemic inflammation and malnutrition can contribute to a reduced albumin. Causes:
- Low production - chronic liver disease, malnutrition
- Loss - gut, kidney(nephrotic syndrome)
- Sepsis - “3rd spacing”
Hypoalbuminaemia in critically ill patients is a poor prognostic factor
Clotting Factors
The liver synthesises Factor V, VII, IX, X, XII, XIII and fibrinogen and prothrombin
In practical terms INR (International normalised ratio) is measured, this is the prothrombin time standardised for age and population expressed as a ratio of ‘normal’.
Deranged clotting is not diagnostic of hepatocellular dysfunction on its own as it could be due to multiple other aetiologies – for example iatrogenic (therapeutic warfarinisation), hereditary thrombophillia, acquired consumption (DIC).
3 things get transaminases >1000
Ischaemia, viruses and toxins (OD)
Pre-hepatic jaundice - causes
Haemolysis
Congestive heart failure
Pre-hepatic jaundice - lab findings
Elevated unconjugated bilirubin
Reduced haemoglobin Reduced haptoglobin
Raised LDH
Hepatic jaundice - Causes
Acute or chronic liver failure Gilbert syndrome
Crigler-Najjar syndrome Viral Hepatitis
Alcoholic Hepatitis
PBC
Hepatic jaundice - Lab Findings
Elevated Unconjugated bilirubin
Raised Aminotransferases Synthetic dysfunction may be present
Gilbert’s: deficiency in UDP-glucoronyl transferase. Crigler-Najjar is a severe form of this.
Post-Hepatic Jaundice - Causes
Obstruction of the biliary tree from any cause (Think intraluminal – Stones, strictures, Luminal – Mass/Neoplasm, Inflammation e.g. PSC/PBC,
Extra-luminal – Pancreatic Ca, cholangio Ca
Post-Hepatic Jaundice - Lab Findings
Elevated conjugated bilirubin Elevated bilirubin in the urine [Dark urine pale stools]
Cirrhosis LFTs
Reasonably normal unless they are decompensating.
Acute Liver Failure LFTs
Wildly elevated liver enzymes and deranged clotting.
Albumin may be normal as it doesn’t immediately fall.
Pts will have rising bilirubin as they progress.
Cholestasis LFTs
Predominantly raised ALP. Others may be mildly raised.
Acute Alcohol Abuse LFTs
Raised gamma GT, mild rise in other enzymes
Amylase
high serum levels in acute pancreatitis (usually >10x upper limit of normal)
Creatine kinase
Most widely used as a marker of muscle damage (CK-MM = skeletal muscle, CK-MB (1&2) = cardiac muscles.)
Raised levels due to:
- Physiological: Afro-Caribbean (<5x upper limit of normal)
- Pathological: Duchenne Muscular Dystrophy (>10xULN), MI (>10xULN), Statin related myopathy, Rhabdomyolysis
Brain Natriuretic Peptide (BNP)
A natriuretic hormone that is primarily released from the ventricles in the heart
Released in response to ventricular stretch, has roles in reducing systemic vasoconstriction, sodium retention and renal sympathetic activity.
Levels of <100 are highly specific for excluding heart failure, >400 is highly sensitive for heart failure
Confounding factors to interpretation include CKD
NT-proBNP is more sensitive than BNP and has greater prognostic value
Troponin
Troponin I/T = myocardial injury biomarker
Measure at 6 hours and then at 12 hours post onset of chest pain (100% Se and 98% Sp at 12-24 hours). Rise at 4-6 hours post MI. Peak at 12-24 hours post MI.
Remains elevated for 3 – 10 days.
None of the current cardiac biomarker levels rise quickly enough to aid in decisions regarding thrombolysis.
Normal GFR & age related decline
120ml/hr.
Age-related decline of approx 1ml/hr/yr.
Renal Clearance
Clearance = the volume of plasma that can be completed cleared of a marker substance in a unit of time.
If marker is not bound to serum proteins, freely filtered by the glomerulus, and not secreted/reabsorbed by tubular cells, then clearance = GFR.
Gold standard measure of GFR = inulin. But requires steady state infusion and difficult to assay so it is reserved for research purposes only.
Creatinine is endogenous marker. This is used in clinical practice to measure renal function. Very variable between individuals and therefore it is best to monitor the trend and use it to look for change over time. Creatinine is a byproduct of muscle turnover, so muscular individuals will have a higher creatinine than others. Age, sex and ethnicity also affect levels.
Different equations use the serum creatinine with variable combinations of age, weight, sex and ethnicity to estimate GFR e.g. Cockcroft-Gault and MDRD (modification of diet in renal disease study). Currently we use CDK-EPI equation.
Urine Examination - Single Sample
Dipstick testing - sensitive to albumin but not bench jones proteins, -ve for blood reliably excludes haematuria
Microscopic examination
Proteinuria quantification (protein:creatinine ratio (PCR))
Urine Examination - 24 hour collection
Proteinuria quantification (superceded by PCR above)
Creatinine clearance estimation
Electrolyte estimation
Stone forming elements
Urine microscopy
Crystals (stones)
Red blood cells (stones, UTI)
White blood cells (UTI, glomerulonephritis)
Casts (glomerulonephritis)
Bacteria (UTI)
AKI definition
Rise in serum creatinine over 26.5 in 48h or to 1.5x baseline in 48h (3x is severe). It can also be defined as a urine output of less than 0.5mls/kg/hr
AKI - causes
Pre-renal – reduced renal perfusion with no structural abnormality pof the kidney, it can become renal if the ischaemia leads to necrosis. Responds to volume replacement
Renal – vascular, glomerular, tubular or interstitial
Post-renal – characterised by obstruction to urinary flow, glomerular filtration requires a pressure gradient, reversal can lead to scarring and permanent renal impairment
Indications for emergency dialysis
1) Pulmonary oedema
2) Refractory hyperkalaemia
3) Metabolic acidosis
4) Uraemic encephalopathy
5) Also some drug toxicity (lithium for example)
CKD - Causes
Diabetes Atherosclerotic renal disease Hypertension Chronic Glomerulonephritis Infective or obstructive uropathy Polycystic kidney disease
Consequences of CKD
Progressive failure of homeostatic function
- Acidosis
- Hyperkalaemia
Progressive failure of hormonal function
- Anaemia (loss of EPO synthesis)
- Renal Bone Disease (secondary hyperparathyroidism due to low Vit D)
Cardiovascular disease:
- Vascular calcification and subsequent atherosclerosis (biggest mortality in CKD)
- Uraemic cardiomyopathy
Uraemia and Death
Renal Replacement Therapy in CKD
Dialysis: haemodialysis, peritoneal
Transplant
