recommended reading lecture notes in clinical biochemistry 7 th edition g beckett, s walker, p rae,...
TRANSCRIPT
![Page 1: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/1.jpg)
Recommended Reading
Lecture Notes in Clinical Biochemistry 7th EditionG Beckett, S Walker, P Rae, P Ashby (Blackwell publishing)
Clinical Chemistry 6th EditionW J Marshall, S K Bangert (Pubslished by Mosby)
An illustrated Colour text - Clinical Biochmeistry 3rd editionAlan Gaw et al (Churchill Livingston)
Handbook of Clinical biochmeistry 1st EditionR Swaminathan (Oxford University Press)
Clinical Chemistry in diagnosis and treatmentPhilip Mayne (Edward Arnold)
A Guide to Diagnostic Clinical Chemistry 3rd EditionWalmsely & White (Blackwell)
![Page 2: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/2.jpg)
Clinical Biochemistry of Liver Disease
Dr Vivion CrowleyConsultant Chemical PathologistSt James’s Hospital
![Page 3: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/3.jpg)
75 yr old female presented to her GP
C/O dyspepsia and “back “ pain
Background hx: •Breast Ca – Rx with mastectomy, Tamoxifen•Variegate Porphyria•Type 2 Diabetes mellitus•Subclinical Hypothyroidism
GP requested Liver Function Tests (Liver Profile)
Illustrative case History
![Page 4: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/4.jpg)
Albumin 43 (34-48) g/L
Total Bilirubin 7 (0 – 21) umol/L
Alkaline Phosphatase 67 (35 -104) IU/L
GGT 93 (5 – 36) IU/L
Alanaine transaminase (ALT) 40 (6 – 31) IU/L
![Page 5: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/5.jpg)
In view of abnormal LFTs the GP ordered further investigations
•Anti Smooth Muscle abs - neg•Anti Mitochondrial abs - neg
•Alpha-1 Antitrypsin 1.5 (0.9 – 2.0) g/L
•Caeuroloplasmin 26.2 (20 – 60) mg/dl
•Transferrrin Saturation 34% (15 – 45) %
•PT 14.8 (11.5 – 15.0) s
•APTT 30.4 s (25 – 35) s
![Page 6: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/6.jpg)
Ultrasound of abdomen and pelvis
Liver-Diffuse inhomogenous somewhat echogenic texture-No focal lesion-Bile ducts not dilated
CT scan of abdomen
Liver-Normal size-Subcapsular surface of the liver has a nodular outline-Liver texture has a diffuse slightly coarse appearance
Appearances consistent with Cirrhosis
GP requested imaging studies in view of negative blood tests
![Page 7: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/7.jpg)
Learning Point
• The only indicator for the presence of underlying cirrhosis in this patient were her mildly abnormal LFTs
![Page 8: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/8.jpg)
What are the functions of the liver?
•Key role in intermediary metabolisme.g. gluconeogenesis, glycolysis, ketogeneis, lipid synthesis
•Protein synthesis – including many plasma proteins and blood clotting factors
•Bile secretion and role in digestion
•Primary site of xenobiotic detoxification -drug and toxin metabolism
•Ureagenesis - ? Role in acid-base balance
![Page 9: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/9.jpg)
What are Liver Function Tests (LFTs)
Total Bilirubin -Conjugated vs. Unconjugated-Anion transport
Alkaline Phosphatase (ALP)-Reference range varies with age – higher in childhoodand adolescence-Isoenzymes e.g. bone, liver, intestine, malignancy-Bile flow
Gamma-glutamyl transferase (GGT)-Sensitive indicator of liver disorder-Cholestasis-Induced by many drugs and toxins e.g. C2H5OH,pheytoin, barbiturates, ? statins
![Page 10: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/10.jpg)
Transaminases-Alanine aminotransferase (ALT)-Aspartate aminotransferease (AST)-ALT is more liver specific-AST is also found in cardiac and skeletal muscle-Hepatocellular integrity
Albumin- Plasma transport protein-Assesses Protein synthesis in liver
Prothrombin time-Extrinsic pathway of coagulation-Reflects protein synthetic function
![Page 11: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/11.jpg)
What role do LFTs in clinical management ?
Detecting the presence of liver disease
Indicating the broad diagnostic category of the liver disease
Monitoring treatment
![Page 12: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/12.jpg)
Specialised Liver-related testsViral Hepatitis Screen – A, B, C etc.
Autoimmune Heaptitis screen – AMA, ASMA,
Serum protein electrophoresis
α1- antitrypsin
α fetoprotein (AFP)
Transferrin Saturation/Ferritin/HFE Genotyping
Caeruloplasmin, Plasma/Urine Copper
Ultrasound scan, CT, MRI
Biopsy
![Page 13: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/13.jpg)
Clinical History
C2H5OH Hx
Family Hx – Haemochromatosis, Wilson Disease,
Drug Hx – What medication is the patient taking?
Travel Hx – Recent travel, Blood transfusions
![Page 14: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/14.jpg)
Bilirubin production and metabolism
UDPGlucoronosyltransferase
![Page 15: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/15.jpg)
Hyperbilirubinaemia
•Jaundice evident with Bilirubin levels 35-70μmol/L•Normally 95% of plasma bilirubin is unconjugated
Unconjugated - prehepatic*(No bilirubinuria)
•Haemolyis•Resolving haematoma•Gilbert’s Syndrome•Crigler-Najjar syndrome
Conjugated – Hepatic/posthepatic(Bilirubinuria)
•Hepatocellular diseases•Cholestatic diseases•Dubin-Johnson**•Rotor’s syndrome**
*Except in Nephrotic syndrome
**Benign congenital conjugated hyeprbilirubinaemia
![Page 16: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/16.jpg)
![Page 17: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/17.jpg)
Gilbert’s Syndrome
Present in 5% of the population
•Males > females
•Genetic origin – insertion of TA in promoter region of UGT-1A gene
•Exacerbated by fasting and illness
•Confirm conjugated hyperbilirubinaemia
•Rule out haemolysis FBC, Reticulocyte count
•Rule out underlying liver disease -
![Page 18: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/18.jpg)
Causes of neonatal jaundice
Unconjugated bilirubin level > 300μmol/L may be associatedwith Kernicterus (brain damage due to uptake of unconjugated bilirubin)
![Page 19: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/19.jpg)
Patterns of LFTs
Hepatocellular •Predominant elevation in AST/ALT –
Cholestatic•Predominant elevation in ALP with GGT ± Bilirubin
Mixed•Elevation in both AST/ALT, and ALP/GGT ± Bilirubin
![Page 20: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/20.jpg)
Causes of a Hepatocellular Pattern of LFTs
Marked elevations in ALT/AST > x5 URL(patient likely to be symptomatic)•Viral hepatitis•Ischaemic hepatitis•Autoimmune hepatitis•Drug/toxins e.g. alcoholic hepatitis
Mild/Moderate elevations in ALT/AST < x5 URL(patient may be asymptomatic)•Chronic Hepatitis•ALD•NAFLD/NASH – associated with obesity, T2DM, Hyerlipidaemia•Metabolic liver disease - HH, WD, A1AT•Drugs•Autoimmune LD
![Page 21: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/21.jpg)
Approach to an asymptomatic patient with elevated ALT/AST
Elevated AST/ALT
Repeat test
Normal Still Elevated
Check CK Elevated
Normal
Likely Liver Aetiology
Drug Hx etc Viral serologyAI hepatitis screenFe/TIBC/Ferritin/HFE genotypingCaeuruloplasmin if < 40 yrA1ATCoeliac screen
Ultrasound scanMRI/CTBx
? Muscleproblem
![Page 22: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/22.jpg)
Causes of a Cholestatic Pattern of LFTs
Elevated ALP and GGT ± Bilirubin, relative to transaminases
Intrahepatic(Bilirubin not elevated)
•Medications•TPN•Sepsis•Postoperative•PBC•Alcoholic hepatitis•Liver mets•Pregnancy-related•CCF
Extrahepatic(Bilirubin elevated)
•Cholelithiasis (CBD)•Malignancy – HOP, •Primary sclerosing cholangitis
GGT is useful in differentiating Liver as a cause of elevated ALP
![Page 23: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/23.jpg)
An approach to the patient with isolated elevation in ALP
Elevated ALP
What is GGT?Normal
?bone, placenta,Intestine etc.
Elevated
US/CT/MRI
Biliary dilation Focal mass No abnormality
Medications PBC -AMA
Consider other causes
Specialised investigations
![Page 24: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/24.jpg)
Other LFTs
Serum ammonia -used for investigation of hepatic encephalopathy-lacks sensitivity and specificity-useful for investigation of urea cycle disorders
Serum LDH-included in LFTs in SJH-5 isoenzymes – heart, erythrocytes, skel mus, liver, others-not specific for liver - ? role in ischaemia-related abnormal LFTs-useful in monitoring certain malignancies e.g. B-cell lymphoma- “not really a LFT”
![Page 25: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/25.jpg)
Reference Ranges for LFTs
Biochemistry Department, St James’s Hopsital
Albumin 35-50 g/L
Bilirubin <17 umol/L
ALP* 40-120 IU/L*
AST 7-40 IU/L
ALT 7-35 IU/L
GGT 10-55 IU/L
* NB: Reference Range is age related
![Page 26: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/26.jpg)
24 yr old male
Insurance medical showed abnormal LFTs ? Cause
Albumin 42 (35-50 g/L)
Bilirubin 38 (<17 umol/L)
ALP 98 (40-120 IU/L)
AST 30 (7-40 IU/L)
ALT 28 (7-35 IU/L)
GGT 37 (10-55 IU/L)
What further tests are indicated?
What is the most likely cause of raised Bilirubin?
Case 1
![Page 27: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/27.jpg)
35 yr old female with a 4/52 hx of-malaise, anorexia, upr abdominal pain, ?haematuria-O/E Icteric
Alb 35
Bilirubin 126
ALP 250 (40-120)
AST 1459
ALT 2009
GGT 331
What further investigations are indicated?
What fraction of her bilirubin is elevated and how does thisimpact on her “haematuria”?
Case 2
![Page 28: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/28.jpg)
You are phoned about the following results and asked to comment on the ALP which appears to be elavated?
Pt is a 17 yr old male – clinical details “still growing”
Alb 46
Bilirubin 12
ALP 220 (40-120)
AST 20
ALT 20
GGT 9
What is the likely cause for the elevated ALP?
Which isoenzyme is increased?
Case 3
![Page 29: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/29.jpg)
48yr old female is attending a lipid-clinic -polygenic hypercholesterolaemia-On atorvastatin 20mg/d for 2 years-C/o tired fatigue, malaise
Alb 42
TBilirubin 8
ALP 250 (40-120)
AST 38
ALT 26
GGT 220
LFTs measured 6/12 previously were normal
What further investigations would you perform?
What is the differential diagnosis?
Case 4
![Page 30: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/30.jpg)
37 yr old male is referred to a lipid clinic with ? Mixed hyperlipidaemia(Chol 7.0 Trigs 5.2)-BMI 35, WC=120cm-Normotensive-Otherwise clinically well
Fasting Glucose 6.8 mmol/L
Alb 38
TBili 15
ALP 82
AST 58
ALT 72
GGT 67 (<55)
What further investigations would you suggest and why?
Case 5
![Page 31: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/31.jpg)
Case 6: Background
Phonecall from a GP regarding LFTs
72yr old female with discomfort in R hypochondrium
No other hx of note
Not on medications
No C2H5OH
![Page 32: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/32.jpg)
Case 6: LFTs
28/4 3/5
Alb (35-50) 39 39
Tbili (3-17) 10 6
AST (7-40) 113 106
ALT (7-35) 95
Alk Phos (40-120) 352 372
GGT (5-40) 874 930
LDH (230-450) 426 495
CK (34-170) 82
![Page 33: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/33.jpg)
Case 6: Further investigations
Mixed cholestatic and hepatocellular liver disease
Fe, TIBC, TS% - all normal
Hepatic Antibody screen – negative
Ultrasound of Upr Abdomen recommended
Gallstones diagnosed
![Page 34: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/34.jpg)
Case 7: Background
•47 yr old male•Hx – malaise and ?icterus (confirmed in sclera)•No recent hx C2H5OH excess or medication
6/5 12/5
Alb 45 43
TBili 181 242
Alk Phos 454 408
GGT 813 428
AST 344 75
ALT 707
![Page 35: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/35.jpg)
Case 7: Dx
•Predominant hepatitic picture
•Resolving to cholestatic LFTs
Probable acute viral hepatitis
![Page 36: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/36.jpg)
Case 8
24 yr old male-Vague hx of feeling unwell, also wt loss >7Kg-? Eating disorder/psychiatric illness
7/3 4/4
Alb 51 50
Tbili (3-17) 93 48
Conj Bili 9
Alk Phos 74 84
GGT 14 18
AST 25 23
![Page 37: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/37.jpg)
Case 8: Further Investigations
FBC and Reticuloctye count – normal
Viral Hep screen – normal
Hep antibody screen – normal
U/S – normal
Biochmeical Dx: -unconjugated Hyeprbilirubinaemia (Gilbert’s syndrome) -confirmed by genetics
![Page 38: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/38.jpg)
Case 9: Why the elevated LFTs?
52 yr old male
No medical hx of note
Not on regular medications
Non-specific hx
Routine Bloods done by GP
“Family Hx IHD” written on request form
![Page 39: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/39.jpg)
Case 9: Results
Fasting Lipid and Glucose – unremarkable
AST = 243, LDH = 1525 (230-450)
GGT = 85 (10-55) other LFTs normal
GP surprised at the raised AST
? Further investigations
![Page 40: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/40.jpg)
Case 9: Further Investigations
ALT = 50 (7-35)
CK 1191 (29-195)
CK-MBmass = 132 (<12)
CK-MB fractionation 10% (<6%)
![Page 41: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/41.jpg)
Case 9: Dx
GP practice contacted:-Informed by Registrar that results were of concern-needed to be communicated to GP-1day later Consultant phoned to see if action had been taken-Pt contacted and advised to present to A/E SJH
Troponin T = 3.25 (<0.01)
Acute Coronary Syndrome (Acute MI)
PTCA and stenting performed
![Page 42: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/42.jpg)
Paracetamol Overdose
•Hepatic necrosis observed within 36-72 hours•Accumulation of breakdown product NAPQI
![Page 43: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/43.jpg)
Early diagnosis and treatment of paracetamol OD is essential
•Ideally before 12 hours post ingestion•N-acetylcysteine (Parvolex) is an effective agent
![Page 44: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/44.jpg)
Iron Overload Syndromes
Primary:
Hereditary Haemochromatosis (HH)
Secondary:
Non HH CirrhosisIneffective erythropoiesis – sideroblastic anaemia, ThalassaemiaMultiple transfusionsBantu siderosisPorphyria Cutanea Tarda (PCT)
![Page 45: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/45.jpg)
Hereditary Haemochromatosis
Autosomal recessive
Mutations in HFE gene-C282Y -H63D
93% associated with homozygosity C282Y +
6% associated with compound heterozygosity C282Y + H63D
1% No mutations identified
![Page 46: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/46.jpg)
Clinical presentation of HH
Males > females
Usually in middle age
Clinical presentation caused by iron accumulation in
Liver – fatty change Cirrhosis Pancreas – DiabetesHeart – dilated cardiomyopathyJoints – arthropathyPituitary – secondary hypogonadism (males > females0Testses – primary hypogonadism (rarer)Parathyroid - hypocalceamia
![Page 47: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/47.jpg)
Diagnosis of HH
•Increased Transferrin Saturation (Plasma Fe/TIBC)
55% - genotype45-55% - may consider genotype
•Increased Ferritin
•HFE genotype
•Liver Biopsy
•Liver Iron content
![Page 48: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/48.jpg)
Figure A
C282Y H63D
1 2 3 1 2 3
1. Homozygous mutant
2. Heterozygous
3. Wild type (normal)
1. Homozygous mutant
2. Heterozygous
3. Wild type (normal)
![Page 49: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/49.jpg)
Case Example : Haemochromatosis51yr old male
Total protein 71
Total Bilirubin 14
Alk Phos 82
GGT 39
AST 44
ALT 92
Serum Fe 38
TIBC 41
Transferrin sat 93%
Ferritin 1,316
HFE genotype C282Y homozygous –Hereditary Haemochromatosis
![Page 50: Recommended Reading Lecture Notes in Clinical Biochemistry 7 th Edition G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing) Clinical Chemistry 6](https://reader030.vdocuments.site/reader030/viewer/2022032516/56649c755503460f949285e1/html5/thumbnails/50.jpg)
Wilson disease
Autosomal recessive
Associated with mutations in ATP7B (Cu transporting P type ATPase)
Clinical presentation – Children and adults usually < 40 years
•CNS – extrapyramidal system, Kayser-Fleischer rings in cornea•Liver – fatty liver, cirrhosis,acute fulminant hepatic failure•Kidney, Haemolytic anaemia
Dx:Low plasma caeruloplasminIncreased Urinary Cu excretion (Penicillamine Challenge Test)Liver Bx – measure Cu content