Interpreting LFTs Flashcards
(83 cards)
1
Q
What are the two primary reasons for requesting LFTs?
A
- To confirm a clinical suspicion of potential liver injury or disease
- To distinguish between hepatocellular injury (hepatic jaundice) and cholestasis (post-hepatic obstructive jaundice)
2
Q
What is cholestasis?
A
The reduction or blockage of bile flow. Can be caused by disorders of the liver, bile duct or pancreas.
3
Q
What are the 7 components of LFTs?
A
- Alanine transaminase (ALT)
- Aspartate aminotransferase (AST)
- Alkaline phosphatase (ALP)
- Gamma-glutamyl transferase (GGT)
- Bilirubin
- Albumin
- Prothrombin time (PT)
4
Q
Which components of LFTs are used to assess the liver’s synthetic function?
A
Albumin, prothrombin time, bilirubin
5
Q
Which components of LFTs are used to distinguish between hepatocellular damage and cholestasis?
A
AST, ALT, ALP and GGT
6
Q
LFT reference ranges:
A
7
Q
Where is ALT found in high concentrations?
A
Hepatocytes
8
Q
When would ALT enter the blood (i.e. raised ALT)?
A
Following hepatocellular injury
9
Q
Where is ALP concentrated?
A
Liver, bile duct and bone tissues
10
Q
Is ALT or ALP more specific for liver disease?
A
ALT (as ALP also found in bile duct and bone tissues)
11
Q
What is ALP often a useful marker of?
A
Cholestasis (due to increased synthesis)
12
Q
What would a greater than 10-fold increase in ALT and a less than 3-fold increase in ALP be suggestive of?
A
Predominantly hepatocellular injury
13
Q
What would a less than 10x increase in ALT and more than 3x increase in ALP indicate?
A
Cholestasis
Note; it is possible to have a mixed picture involving both hepatocellular injury and cholestasis
14
Q
If there is a rise in ALP, which enzyme is it important to review?
A
GGT
15
Q
Where is GGT predominantly found?
A
Liver and gallbladder
16
Q
What are 4 causes of a raised GGT?
A
- Biliary epithelial damage
- Bile flow obstruction
- Response to alcohol
- Response to drugs e.g. phenytoin
17
Q
What is a markedly raised ALP with a raised GGT highly suggestive of?
A
Cholestasis
18
Q
What is a raised ALP in the absence of a raised GGT suggestive of?
A
Non-hepatobiliary pathology
ALP is also present in bone so anything that causes increased bone breakdown can elevate ALP
19
Q
Give 2 bone causes of a high ALP?
A
- Bone mets
- Healing fracture
20
Q
How would hyperthyroidism affect ALP levels? Why?
A
May increase ALP levels
Overt hyperthyroidism is associated with accelerated bone remodeling, reduced bone density, osteoporosis, and an increase in fracture rate
21
Q
What are causes of an isolated rise in ALP?
A
- Bone metastases
- 1ary bone tumours (e.g. sarcoma)
- Vitamin D deficiency
- Recent bone fractures
- Renal osteodystrophy
22
Q
What is renal osteodystrophy?
A
A form of metabolic bone disease seen in patients with chronic renal insufficiency characterised by bone mineralisation deficiency due to electrolyte and endocrine abnormalities.
Patients present with osteomalacia, osteonecrosis and pathologic fractures.
23
Q
Compare ALT to ALP levels in a primarily hepatocellular pattern of injury
A
ALT is raised markedly compared to ALP
24
Q
Compare ALT to ALP levels in a primarily cholestatic pattern of injury
A
ALP is raised markedly compared to ALT
25
If the patient is jaundiced but ALP and ALT levels are normal, what is going to be risen?
Bilirubin
26
What is the most common cause of an isolated rise in bilirubin?
Gilbert's syndrome
27
What is Gilbert's syndrome?
An inherited condition where the liver's ability to conjugate bilirubin is impaired. In times of fatigue/stress etc, that patient can become temporarily jaundiced. It is often **not serious** with no **side effects**.
28
What is another cause of an isolated rise in bilirubin?
Haemolysis e.g. haemolytic anaemia
29
What blood tests should be done in suspected cases of haemolysis?
* Blood film
* FBC
* Reticulocyte count
* Haptoglobin
* LDH levels
30
What is the normal life span of a RBC?
120 days
31
What may a FBC show in haemolysis?
Reduced haemoglobin indicates anaemia (normocytic or macrocytic)
32
What may a blood film show in haemolysis?
Abnormal RBCs e.g. spherocytes, schistocytes etc
33
What may a reticulocyte count show in haemolysis?
Elevated reticulocytes
34
What is haptoglobin?
Haptoglobin is the protein produced by the liver that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds to free haemoglobin.
35
What may haptoglobin levels show in hameolysis?
Reduced haptoglobin
36
What may LDH levels show in haemolysis?
LDH levels elevated as LDH is intracellular so released when RBCs rupture
37
Is the bilirubin conjugated or unconjugated in haemolytic anaemia?
Unconjugated (no effect on urine/stools)
38
What are the 4 main synthetic functions of the liver?
1. Conjugation and elimination of bilirubin
2. Albumin
3. Clotting factors
4. Gluconeogenesis
39
What 4 investigations can be done to assess synthetic liver function?
1. Serum bilirubin
2. Serum albumin
3. Prothrombin time (PT)
4. Serum blood glucose
40
What is bilirubin?
Breakdown product of haem
41
Describe the conjugation process of bilirubin
1. RBC breakdown in spleen gives unconjugated bilirubin
2. Unconjugated bilirubin is conjugated in the liver to give conjugated bilirubin
3. Conjugated bilirubin then is excreted in bile into the 2nd part of duodenum (ampulla of vater)
4. In the colon, bacteria convert conjugated bilirubin into **urobilinogen**
5. Most urobilinogen is converted into sterocobilin and excreted via faeces
6. Some urobilinogen is reabsorbed to be recycled or sent to kidneys where it is converted to **urobilin** and excreted via urine
42
Which form of bilirubin gives faeces its brown colour?
Stercobilin
43
Which form of bilirubin gives urine its yellow colour?
Urobilin
44
What is the cause of **dark urine** in post-hepatic jaundice?
Urobilinogen
45
What type of jaundice does malaria cause?
Pre-hepatic (haemolytic anaemia)
46
In pre-hepatic jaundice:
a) what type of bilirubin is raised?
b) colour of skin?
c) colour of urine?
d) colour of stool?
Why?
a) unconjugated bilirubin
b) yellow
c) normal
d) normal
As unconjugated bilirubin is **insoluble**
47
In post-hepatic jaundice:
a) what type of bilirubin is raised?
b) colour of skin?
c) colour of urine?
d) colour of stool?
Why?
a) conjugated
b) yellow
c) dark
d) pale
As conjugated bilirubin is **soluble** so can pass into urine as **urobilinogen** (causes dark urine)
48
In obstructive post-hepatic pathology, how many stools appear? Why?
Stools appear pale, bulky and difficult to flush
As bile and pancreatic lipases are unable to reach the bowel because of the blockage so fat cannot be absorbed
49
What type of jaundice is indicated by;
a) normal urine + normal stools
b) dark urine + normal stools
c) dark urine + pale stools
a) pre-hepatic
b) intra-hepatic
c) post-hepatic
50
What are 3 mechanisms behind unconjugated hyperbilirubinaemia?
1. Haemolysis → haemolytic anaemia
2. Impaired conjugation → Gilbert's syndrome
3. Impaired hepatic uptake → drugs, congestive cardiac failure
51
What are 2 major causes of conjugated hyperbilirubinaemia?
1. Hepatocellular injury
2. Cholestasis
52
What is albumin? Function?
Albumin is synthesised in the liver and helps to bind water, cations, fatty acids, and bilirubin. It also plays a key role in **maintaining the oncotic pressure** of blood.
53
What are 3 mechanisms causing **hypo**albuminaemima?
1. **Excessive losses** → loss of protein due to protein losing enteropathies or nephrotic syndrome
2. **Decreased production** → liver disease e.g. cirrhosis
3. **Inflammation**
54
What is a protein losing enteropathy?
**A pathological condition in which there is an increased loss of proteins through the gastrointestinal tract**, which leads to low serum proteins.
E.g. severe burns
55
Why can inflammation lead to hypoalbuminaemia? Is this permanent?
Inflammation triggers an acute phase response which **temporarily** decreases the liver's production of albumin
56
What is prothrombin time? Which pathway is it measuring?
A measure of the blood's coagulation tendency (i.e. clotting time).
Directly assesses the **extrinsic pathway**.
57
What are two 2ary causes of an increased PT?
1. Anticoagulant drug use
2. Vitamin K deficiency
58
Why can a vitamin K deficiency lead to an increased PT time?
Some clotting factors are vitamin K dependent
59
How can hepatic pathology affect PT? Why?
Increase - liver synthesises clotting factors
60
What is gluconeogenesis?
A metabolic pathway that results in the **generation of glucose** from certain **non-carbohydrate** substrates
61
Why can assessment of serum blood glucose provide an indirect assessment of the liver’s synthesis function?
The liver plays a significant role in gluconeogenesis
62
Is gluconeogenesis affected early or late in liver failure?
Late - one of the last functions to be impaired
63
Common patterns of LFT derangement
64
In **acute** hepatocellular damage, describe;
a) ALT levels
b) ALP levels
c) GGT levels
d) bilirubin
a) markedly raised
b) normal or slightly raised
c) normal or slightly raised
d) slightly or markedly raised
65
In **chronic** hepatocellular damage, describe;
a) ALT levels
b) ALP levels
c) GGT levels
d) bilirubin
a) **normal or slightly raised**
b) normal or slightly raised
c) normal or slightly raised
d) normal or slightly raised
66
In cholestasis, describe;
a) ALT levels
b) ALP levels
c) GGT levels
d) bilirubin
a) normal or slightly raised
b) markedly raised
**c) markedly raised**
d) markedly raised
67
What are 3 common causes of **acute** hepatocellular injury?
a) Poisoning (paracetamol overdose)
b) Infection (hep A & B)
c) Liver ischaemia
68
What types of hepatitis can progress to chronic?
Hep B and C
69
What are 4 common causes of **chronic** hepatocellular injury?
1. Chronic infection (Hep B or C)
2. Alcoholic fatty liver disease
3. Non-alcoholic fatty liver disease
4. Primary biliary cirrhosis
70
What are 3 less common causes of chronic hepatocellular injury?
1. **Wilson's disease** → copper build up damages liver)
2. **Haemochromatosis** → excess iron stored in liver damages it
3. **Alpha-1 antitrypsin deficiency** → 15% develop cirrhosis
71
What is a liver screen?
A batch of investigations focused on ruling underlying causes of liver disease out or in.
72
What does a typical liver screen include?
* LFTs
* Coagulation screen
* Hepatitis serology (A/B/C)
* Epstein-Barr virus (EBV)
* Cytomegalovirus (CMV)
* Anti-mitochondrial antibody (AMA)
* Anti-smooth muscle antibody (ASMA)
* Anti-liver/kidney microsomal antibodies (anti-LKM)
* Anti-nuclear antibody (ANA)
* p-ANCA
* Immunoglobulins – IgM/IgG
* Alpha-1 antitrypsin
* Serum copper
* Ceruloplasmin
* Ferritin
73
What is the purpose of serum copper levels in a liver screen?
To rule of Wilson's disease
74
What is ceruloplasmin?
***Ceruloplasmin*** is a protein that is made in the liver.
Ceruloplasmin is the major **_copper-carrying_** protein in the blood, and in addition plays a role in iron metabolism.
75
What is ceruloplasmin?
**Ceruloplasmin** is a protein that is made in the liver.
Ceruloplasmin is the major **_copper-carrying_** protein in the blood, and in addition plays a role in iron metabolism.
76
What disease can be included/excluded by assessing ceruloplasmin in liver disease?
To rule out Wilson's disease
77
How is ceruloplasmin affected in Wilson's? Why?
Reduced levels
## Footnote
In Wilson disease, **copper is not put in ceruloplasmin** (carrying protein).
78
What disease can be included/excluded by assessing ferritin in liver disease?
Haemochromatosis
79
What disease can be included/excluded by assessing alpha-1 antitrypsin in liver disease?
alpha-1 antitrypsin deficiency
80
Anti-mitochondrial antibodies (AMA) are highly specific of which pathology?
Anti-mitochondrial antibody are highly sensitive and specific marker of **Primary Biliary Cirrhosis**
81
What do high levels of anti-smooth muscle antibodies (ASMA) likely indicate?
Autoimmune hepatitis
82
What disease can a positive ANA test indicate?
Autoimmune; e.g. SLE
83
What can a positive p-ANCA test indicate?
Autoimmune vasculitis e.g. Granulomatosis with polyangitis (formerly known as Wegners Granulomatosis)
