Chempath - LFTs, Cardaic Enzymes and Renal Function

Question 1

Marks of liver synthetic function

Answer 1

Clotting (INR)
Albumin
Glucose

However bare in mind that all of these things can go off by issues not directly cased by the liver.

Question 2

Markers of liver cell damage

Answer 2

Hepatocyte cell damage - ALT, AST
Biliary stasis - ALP, GGT
Bilirubin

Question 3

Aspartate aminotransferase (AST)

Answer 3

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

Question 4

Alanine aminotransferase

Answer 4

Found primarily in the
liver, more sensitive than AST for hepatocyte damage.

Raised when hepatocytes die. AST:ALT =1 supportive of viral hepatitis.

Question 5

Alkaline Phosphatase (ALP)

Answer 5

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)

Question 6

Gamma GT

Answer 6

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

Question 7

Alpha fetoprotein

Answer 7

Tumour marker. Also raised in hepatic damage/regeneration, pregnancy & testicular ca.

Question 8

Albumin

Answer 8

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

Question 9

Clotting Factors

Answer 9

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).

Question 10

3 things get transaminases >1000

Answer 10

Ischaemia, viruses and toxins (OD)

Question 11

Pre-hepatic jaundice - causes

Answer 11

Haemolysis

Congestive heart failure

Question 12

Pre-hepatic jaundice - lab findings

Answer 12

Elevated unconjugated bilirubin
Reduced haemoglobin Reduced haptoglobin
Raised LDH

Question 13

Hepatic jaundice - Causes

Answer 13

Acute or chronic liver failure Gilbert syndrome
Crigler-Najjar syndrome Viral Hepatitis
Alcoholic Hepatitis
PBC

Question 14

Hepatic jaundice - Lab Findings

Answer 14

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.

Question 15

Post-Hepatic Jaundice - Causes

Answer 15

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

Question 16

Post-Hepatic Jaundice - Lab Findings

Answer 16

Elevated conjugated bilirubin Elevated bilirubin in the urine [Dark urine pale stools]

Question 17

Cirrhosis LFTs

Answer 17

Reasonably normal unless they are decompensating.

Question 18

Acute Liver Failure LFTs

Answer 18

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.

Question 19

Cholestasis LFTs

Answer 19

Predominantly raised ALP. Others may be mildly raised.

Question 20

Acute Alcohol Abuse LFTs

Answer 20

Raised gamma GT, mild rise in other enzymes

Question 21

Amylase

Answer 21

high serum levels in acute pancreatitis (usually >10x upper limit of normal)

Question 22

Creatine kinase

Answer 22

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

Question 23

Brain Natriuretic Peptide (BNP)

Answer 23

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

Question 24

Troponin

Answer 24

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.

Question 25

Normal GFR & age related decline

Answer 25

120ml/hr. Age-related decline of approx 1ml/hr/yr.

Question 26

Renal Clearance

Answer 26

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.

Question 27

Urine Examination - Single Sample

Answer 27

Dipstick testing - sensitive to albumin but not bench jones proteins, -ve for blood reliably excludes haematuria Microscopic examination Proteinuria quantification (protein:creatinine ratio (PCR))

Question 28

Urine Examination - 24 hour collection

Answer 28

Proteinuria quantification (superceded by PCR above) Creatinine clearance estimation Electrolyte estimation Stone forming elements

Question 29

Urine microscopy

Answer 29

Crystals (stones) Red blood cells (stones, UTI) White blood cells (UTI, glomerulonephritis) Casts (glomerulonephritis) Bacteria (UTI)

Question 30

AKI definition

Answer 30

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

Question 31

AKI - causes

Answer 31

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

Question 32

Indications for emergency dialysis

Answer 32

1) Pulmonary oedema 2) Refractory hyperkalaemia 3) Metabolic acidosis 4) Uraemic encephalopathy 5) Also some drug toxicity (lithium for example)

Question 33

CKD - Causes

Answer 33

``` Diabetes Atherosclerotic renal disease Hypertension Chronic Glomerulonephritis Infective or obstructive uropathy Polycystic kidney disease ```

Question 34

Consequences of CKD

Answer 34

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

Question 35

Renal Replacement Therapy in CKD

Answer 35

Dialysis: haemodialysis, peritoneal Transplant