Chemical Pathology Flashcards
1
Q
How do you calculate osmolality?
A
Osmolality = 2 (Na+K) + Urea + Glucose Units = mosm/kg
2
Q
How is the anion gap calculated?
A
Anion gap = Na + K - Cl - bicarb
3
Q
What is a normal anion gap?
A
18 mM
4
Q
pH 7.65 pCO2 2.8 kPa Bicarb 24 mM (normal) PO2 15 kPa What is the acid base abnormality?
A
Respiratory alkalosis
5
Q
pH 7.10 pCO2 1.3 kPa PO2 15 kPa What is the acid base abnormality? With an anion gap of 50, what could be causing this?
A
Metabolic acidosis.
Could be ketones but if negative could be methanol, ethanol, lactate.
Metformin in overdose can cause a lactic acidosis.
6
Q
Which diabetic drug in overdose can cause a lactic acidosis?
A
Metformin
7
Q
What is plasma?
A
Supernatant of unclotted blood. Serum in the supernatant of clotted blood.
8
Q
What is the normal total protein range of plasma?
A
60-80 g/L
9
Q
Examples of alpha-1 globulins
A
Alpha-1-antitrypsin
Alpha-1-acid Glycoprotein
10
Q
Examples of alpha-2 globulins
A
Haptoglobin
Caeruloplasmin
Alpha-2-macroglobulin
11
Q
Examples of Beta globulins
A
Transferrin
Apo B
Complement
12
Q
Examples of gamma globulins
A
IgG, IgA, IgM, IgD, IgE
13
Q
What is the normal plasma concentration of albumin? How does it change in disease?
A
33-47 g/L
Almost always low in disease, increase only seen in severe dehydration.
14
Q
How do Kwashiorkor and Marasmus differ?
A
Kwashiorkor: Sufficient calorie intake, but with insufficient protein consumption characterized by oedema, irritability, anorexia, ulcerating dermatoses, and an enlarged liver with fatty infiltrates.
Marasmus: inadequate energy intake in all forms, including protein. Look emaciated.
15
Q
What are the three main reasons behind a low albumin?
A
Decreased production
Increased extra vascular loss
Increased GI and renal loss
16
Q
What is alpha-1-antitrypsin?
A
Major antagonist of serine proteases including neutrophil elastase. Positive acute phase reactant
17
Q
What does haptoglobin do?
A
Binds free haemoglobin and transports it to the spleen.
There are low levels in haemolysis.
18
Q
What is caeruloplasmin and what disease is associated with it?
A
Copper containing protein.
Autosomal recessive deficiency causes Wilson’s disease - body retains copper in tissues resulting in liver disease, neurological and psychiatric problems, haematological disorders.
19
Q
What does transferrin do?
A
Plasma iron transport, negative acute phase protein.
20
Q
A defect in HFE gene causes what disease?
A
Hemochromatosis - membrane protein regulating iron absorption affected causing multisystem iron deposition.
Diabetes, cirrhosis, gonadal/pituitary failure, cardiomyopathy, arthritis, bronzing of skin.
21
Q
Pepperpot skull X-ray sign is associated with…?
A
Myeloma
22
Q
What tumours are associated with raised alpha-feto protein (AFP)?
A
Hepatocellular carcinoma, germ cell tumors, and metastatic cancers of the liver.
23
Q
What tumours are associated with raised Ca 19-9?
A
Pancreatic cancer - levels measured to monitor response to treatment
24
Q
What tumours are associated with Ca-125?
A
Ovarian cancer
25
What tumours are associated with carcinoembryonic antigen (CEA)?
Colorectal carcinoma
26
What tumours are associated with Beta-HCG?
Testicular cancer.
Seminoma, choriocarcinoma, germ cell tumors, hydatidiform mole formation, teratoma with elements of choriocarcinoma, and islet cell tumor.
27
Oligoclonal IgG in CSF may be seen in what?
Demyelinating diseases and some infections
28
What are the protein levels of transudates and exudates?
Transudate protein < 25 g/L
| Exudate protein > 35 g/L
29
How does the pattern of renal disease affect protein excretion?
Glomerular: albumin
Tubular: retinal binding protein and beta-2-microglobulin
Overflow: paraprotein e.g. in myeloma
30
What are the causes of a transudate?
CCF
Liver failure
Hypoalbuminaemia (nephrotic syndrome)
Peritoneal dialysis
31
What are the causes of an exudate?
Parapneumonic effusions
Malignancy
Pulmonary embolism
Pancreatitis, RA, SLE, TB
32
An exudate with protein >40 g/L is very likely caused by what?
Pancreatitis
33
How do you calculate the SAAG?
Serum ascites-albumin gradient (SAAG)
| = serum albumin - ascites albumin
34
What are Light's criteria?
Pleural / serum protein >0.5
Pleural / serum LDH >0.6
Pleural LDH >⅔ times the normal upper limit for serum
2 of 3 = exudate
35
What does the SAAG value suggest? What are the cut-offs?
```
High gradient (>11 g/L) = TB, malignancy, pancreatitis
Low gradient (<11 g/L) = cirrhosis, nephrotic syndrome
```
36
The levels of which protein fall during intravascular haemolysis?
Haptoglobin
37
What can deficient enzyme activity lead to?
Lack of end product
Build-up of precursors
Abnormal, often toxic metabolites
38
What are Wilson's criteria for screening?
1) The condition should be an important health problem.
2) There should be a treatment for the condition.
3) Facilities for diagnosis and treatment should be available.
4) There should be a latent stage of the disease.
5) There should be a test or examination for the condition.
6) The test should be acceptable to the population.
7) The natural history of the disease should be adequately understood.
8) There should be an agreed policy on whom to treat.
9) Economically balanced.
10) Case-finding should be a continuous process, not just a "once and for all" project.
39
What causes PKU?
Phenylketonuria (PKU) is caused by a phenylalanine hydroxylase deficiency which leads to raised levels of phenylalanine in the blood.
40
How is congenital hypothyroidism screened for in newborns?
TSH measured from blood spot on Guthrie card.
| Only 15% inherited, usually dysgenesis/agenesis of thyroid.
41
How is cystic fibrosis screened for in newborns?
Immune reactive trypsinogen (IRT) blood levels are increased. Confirmed with sweat test.
42
How is MCADD screened for in newborns?
Medium chain AcylCoA dehydrogenase screened for using acylcarnitine levels by tandem mass spectrometry
43
What is the acute management for an alert and orientated adult with hypoglycaemia?
Give oral carbohydrates;
Rapid e.g. Lucozade
Longer acting e.g. sandwich
Consider glucagon if deteriorating, refractory or insulin induced.
44
What is the acute management for a drowsy, confused adult with hypoglycaemia but with an intact swallow?
Buccal glucose e.g. Hypostop, glucogel etc.
| Start thinking about IV access and consider glucagon IM/SC
45
What is the acute management for an unconscious adult with hypoglycaemia?
IV access, 50 ml, 50% glucose or 100 ml 20% glucose.
| Consider glucagon if deteriorating, refractory, insulin induced or difficult IV access.
46
What are the symptoms of hypoglycaemia?
Adrenergic: tremors, palpitations, sweating, hunger
Neuroglyopaenic: somnolence, confusion, incoordination, seizures, coma
May be none!
47
What are the main effects of natural glucagon?
- reduce peripheral uptake of glucose
- increase glycogenolysis
- increase gluconeogenesis
- increase lipolysis
48
How does the brain respond to hypoglycaemia? (Hormonally)
Sensed in hypothalamus, activates sympathetic system (catecholamines) and stimulates ACTH and GH production
49
What regulates ketone body production?
Beta-oxidation very sensitive to insulin levels, must be low for ketone production
50
What is muscle glycogen broken down to?
Glucose-6-phosphate which can't be exported to raised glucose levels in hypoglycaemia.
51
pH 6.85
pCO2 2.3 kPa
PO2 15 kPa
What is the acid base abnormality?
Metabolic acidosis
52
What are the problems with measuring blood glucose?
Blood glucose meter has poor precision at low glucose levels and the devices are often poorly maintained. Lab measured venous blood glucose much better but there is a delay in results.
53
What diabetic drugs are common culprits of hypoglycaemic events?
Sulphonylureas (esp. long acting), insulin (long acting can cause hypo's at night) and also beta-blockers, salicylates and alcohol.
54
What can C-peptide levels tell you?
It is a good marker of beta-cell function and can help to differentiate the cause of hypoglycaemia. Blood sample must be placed on ice for accurate reading. C-peptide is fragment left after proinsulin is cleaved to release insulin. Half-life ~30mins, renal clearance
55
What may a very good HbA1c level suggest?
Patient may be having recurrent hypo's
56
What might a patient with lanugo hair on their back have?
Anorexia nervosa - due to malnourishment. Very fine, soft, unpigmented hair usually only seen on fetuses.
57
A large disparity between finger prick measured glucose (4.0) and blood glucose (2.5) at the low end of the scale might be caused by what?
Sugar or something sweet on the finger from where the finger prick sample was taken raising the level. Possible in anorexics trying to hide low blood sugar.
58
What does a low blood glucose, low insulin and low C-peptide suggest?
Appropriate response to hypoglycaemia caused by starvation, exercise, illness, liver failure and endocrine deficiencies e.g. hypopituitarism, adrenal failure
59
What is beta-hydroxybutyrate?
A ketone body. Should be produced from fatty acid oxidation in hypoglycaemia. Others are acetoacetate and acetone.
60
What could cause a neonate to have hypoglyaemia and negative ketones?
A fatty acid oxidation defect. Free fatty acids would be raised.
61
What may cause a hypoglycaemia and a endogenous high insulin level?
Iselet cell tumours (insulinoma)
Sulphonylurea abuse
Islet cell hyperplasia: infant of diabetic mother, Beckwith Weidemann syndrome, nesidioblastosis.
62
What type of tumour is an insulinoma?
Usually small solitary adenoma
10% malignant
8% associated with MEN1
63
A child fitting with a low glucose, high insulin and low C-peptide is caused by what?
Factitious insulin
64
What might cause an elderly smoker to have refractory hypoglycaemia with low insulin, low C-peptide, low FFA and low ketones?
Non-islet cell tumour hypoglycaemia - paraneoplastic syndrome, secretion of big IGF-2 which binds to and activates IGF-1 and insulin receptor, acting as insulin.
65
An adult female with a low glucose, high insulin and low C-peptide could be caused by what?
Factitious insulin
| Antibodies to insulin receptors - bind and stimulate insulin release - IR-Ab present.
66
Which non-diabetic drugs could cause hypoglycaemia?
Quinine - stimulates insulin secretion
| Pentamidine - toxic to Beta-cells, releases pre-formed insulin
67
What is reactive/post-prandial hypoglycaemia?
Low blood glucose following food intake. Can occur following gastric surgery, with hereditary fructose intolerance, early DM.
68
X-linked urea cycle disorder?
Ornithine transcarbamylase deficiency
69
Flags for urea cycle disorders?
- Vomiting without diarrhoea
- Respiratory alkalosis with hyperammonaemia
- Neurological encephalopathy (incl. ADHD)
- Protein rich food avoidance, change in diet
Majority autosomal recessive inheritance
70
A patient with hyperammonaemia, a metabolic acidosis and a high anion gap might have what?
An organic aciduria - a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branched-chain amino acids (leucine, isoleucine, valine), causing a buildup of acids which are usually not present
71
Presentation of an organic aciduria?
Presents in neonates:
- unusual odour (e.g. urine), lethargy, feeding problems
- truncal hypotonia / limb hypertonia, myoclonic jerks
- Hyperammonaemia + metabolic acidosis + high anion gap (not lactate)
- Hypocalaemia, neutropenia, thrombopenia, pancytopenia
72
What is Reye's syndrome?
Classic features: rash, vomiting, liver damage.
Also lethargy, confusion, seizures, decerebration, respiratory arrest, hypoglycaemia.
Can be triggered by salicylates (aspirin), antiemetics, valproate.
Associated with underlying inborn metabolic disorder - require screening
73
How does a chronic intermittent form of an organic aciduria present?
In childhood (rather than neonatal) with recurrent episodes of ketoacidotic coma, cerebral abnormalitites and Reye's syndrome
74
What tests should you do in a patient with suspected Reye syndrome?
- Plasma ammonia
- Plasma / urine amino acids
- Urine organic acids
- Plasma glucose and lactate
- Blood spot carnitine profile
75
What does hypoketotic hypoglycaemia suggest?
A fatty-acid metabolism disorder.
| Get hepatomegaly and cardiomyopathy.
76
What is galactosaemia and what is the most common form?
Disorder of galactose metabolism.
Galactose-1-phosphate uridyl transferase (Gal-1-PUT) most common and most severe.
Raised gal-1-phosphate causes liver and kidney disease.
77
How does galactosaemia present?
In neonates with vomiting, diarrhoea, conjugated hyperbilirubinaemia, hepatomegaly, hypoglycaemia and sepsis (E.coli)
78
If galactose is not removed from the diet of patients with galactosaemia, what occurs?
Galactitiol is formed by the action of aldolase on gal-1-phosphate leading to bilateral cateracts
79
How can you test for galactosaemia?
- Urine reducing substances
| - Red cell Gal-1-PUT
80
What is glycogen storage disease type 1 also know as and what is the deficiency?
von Gierke's disease
Deficiency of glucose-6-phosphatase - unable to break down glycogen to glucose in liver results in increased glycogen storage in liver and kidneys.
81
What signs does someone with glycogen storage disease type 1 get?
Hepatomegaly, nephromegaly, hypoglycaemia, lactic acidosis and neutropenia
82
How can a mitochondria disorder present?
Can affect any organ, any age, and by any mean of inheritance.
83
3 examples of a mitochondrial disorder?
Barth syndrome
MELAS syndrome
Kearns-Sayre syndrome
84
What is Barth syndrome?
Mitochondrial disorder presenting from birth with cardiomyopathy, neutropenia and myopathy
85
What is MELAS syndrome?
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - presents in childhood ~5-15 years
86
What is Kearns-Sayre syndrome?
Mitochondrial disorder presenting between ages 12-30 with chronic progressive external opthalmoplegia, retinopathy, deafness and ataxia
87
How should suspected mitochondrial disorders be investigated?
- Fasting lactate (elevated)
- CSF lactate / pyruvate
- CSF protein
- CK
- Muscle biopsy
- Mitochondrial DNA analysis
88
What pathology is associated with congenital disorders of glycosylation?
Cardiomyopathy, osteopenia, hepatomegaly, dysmorphic features e.g. inverted nipples and subcutaneous fat pads.
Test: analysis of transferrin glycosylation status
89
What are peroxisomal disorders?
Disorder in the metabolism of very long chain fatty acids and biosynthesis of complex phospholipids
90
What problems occur with peroxisomal disorders?
Neonates:
- Severe muscular hypotonia and seizures
- Hepatic dysfunction with mixed hyperbilirubinaemia
- Dysmorphic signs
Infants:
- Retinopathy, sensorineural deafness, mental deficiency
- Hepatic dysfunction
- Late closing large fontanelle, long bone osteopenia, patella calcified stippling
91
What are lysosomal storage diseases?
Causes intraorganelle substrate accumulation leading to organomegaly with consequent dysmorphia and regression.
92
What lab investigations are done to confirm a lysosomal storage disease?
- Urine mucopolysaccharides and/or oligosaccharides
| - Leucocyte enzyme activites
93
How are lysosomal storage diseases treated?
- Bone marrow transplant
| - Exogenous enzyme replacement therapy
94
Definition of intermediary metabolism
Enzyme-catalysed processes within cells that extract energy from nutrient molecules and use that energy to construct cellular components
95
List of normal liver functions
```
Intermediary Metabolism
Protein Synthesis
Xenobiotic Metabolism
Hormone Metabolism
Bile Synthesis
Reticulo-endothelial
```
96
Which two enzymes are contained within the cytoplasm of hepatocytes and measured as part of LFTs? And which one of them rises more in alcohol and cirrhosis?
```
Alanine transferase (ALT)
Aspartate transaminase (AST)
AST rises more in alcohol and cirrhosis
```
97
Where is gamma-glutaryl transpeptidase (GGT) found in the liver? And when raised, what is it most commonly a sign of?
Hepatocytes and epithelium of small bile ducts.
| Elevated in chronic alcohol use but also raised in bile duct disease and hepatic metastasis.
98
Which LFT enzyme is located in sinusoidal and canalicular membranes? And what causes it to become elevated?
```
Alkaline phosphatase (ALP)
Markedly elevated if obstructive jaundice or bile duct damage.
Less elevated in viral hepatitis or alcoholic liver disease i.e. hepatocyte damage.
Other causes of a rise include bone disease (especially metastatic and pregnancy)
```
99
What is the best function of liver function?
Pro-thrombin time (due to short half-life of clotting proteins)
100
What should a urine dipstick show with normal liver function?
No bilirubin, small amount of urobilinogen.
101
When is urobilinogen not detected on a urine dipstick?
In there is extra-hepatic biliary obstruction. Will also have pale stools and dark urine with high conc of bilirubin.
102
What test should be ordered if LFTs are abnormal with a raised bilirubin?
Liver USS to look for dilated ducts or not.
103
What other liver function tests are there other than the standard LFTs?
- Dye tests (indocyanine green / bromsulphalein)
- Breath tests (aminopyrine / galactose)
- Serum bile acids (elevated esp. in cholestatsis of pregnancy and PBC/PSC)
104
What happens LFTs when a patient with Gilberts syndrome fasts?
Get a raised unconjugated bilirubin
105
Which particular commonly used drug can cause cholestatic jaundice?
Augmentin, also flucloxacillin, erythromycin and many other drugs
106
What is Courvoisier's sign/law?
In the presence of a painless palpable gallbladder, jaundice is unlikely to be caused by gall stones.
107
What 3 three can causes ALT and AST to go about 1000?
Viruses
Drugs
Ischaemia
108
What picture is common with LFTs in alcoholic liver disease?
AST:ALT = 2:1
| In viral liver disease AST:ALT <1:1
109
Where are and what do the different zones of the adrenal glands do?
```
From outside to in:
Capsule
Glomerulosa - Aldosterone
Fasiculata - Cortisol
Reticularis - Testosterone
Medulla - Adrenaline
```
110
31 year old presents with profound tiredness. Acutely unwell a few days. Vomiting.
Na: 125, K: 6.5, U 10, Glucose 2.9mM.
FT4 < 5nM TSH > 50mU/l
What's the diagnosis?
Thyroid failure - Primary hypothyroidism plus mineralocoricoid and glucocorticoid deficiency - Addison's disease
= Schmidt's syndrome aka Autoimmune polyendocrine syndrome type 2
111
What is Schmidt's syndrome?
Aka Autoimmune polyendocrine syndrome type 2
| Addison's disease, hypothyoidism and diabetes type I - occur together more commonly than by chance alone.
112
What is the test for Addison's disease?
Short synacthen test - compares cortisol levels before and after 250 mg of tetracosactide (syn ACTH). Check at 30 and 60 mins, should see a steady rise if no adrenal failure.
113
Differential for a 32 year old man with hypertension and an adrenal mass?
Phaeochromocytoma - large tumour
Conn's syndrome - small tumour
Cushing's syndrome
114
What urgent drug treatment is required for a patient newly diagnosed with a phaeochromocytoma?
Alpha-blockade e.g. Phenoxybenzamine + fluids to prevent hypotension.
Later add beta-blockade then prepare for curative surgery.
115
```
Hypertensive 33 year old.
Na 147, K 2.8, U 4.0. Glucose 4.0 mM
Plasma aldosterone raised.
Plasma renin suppressed.
What is the diagnosis ?
```
Conn's syndrome - primary hyperaldosteronism
116
34 year old obese woman with type 2 diabetes, presents with hypertension and bruising.
Na: 146, K: 2.9, U 4.0, Glucose 14.0
Aldosterone <75 (low). Renin low. Diagnosis?
Cushing's syndrome
117
Which dynamic test is used for Cushing's syndrome?
Dexamethasone suppression test
118
What are the causes of Cushing's syndrome?
Exogenous steroids
Pituitary dependent Cushings disease (85%)
Ectopic ACTH (5%)
Adrenal adenoma (10%)
119
An obese 35 year old patient has the following results:
9am cortisol (Monday): 650 nM
Given 0.5 mg dexamethasone every 6 hours for 48 hours
9am cortisol (Wednesday)
Normal obese person - reassure and discharge
120
9am cortisol (Monday): 650 nM
Given 0.5 mg dexamethasone every 6 hours for 48 hours
9am cortisol (Wednesday) 500nM
What is the diagnosis?
Cushing’s syndrome of indeterminate cause.
Need to do high dose dexamethasone suppression test to distinguish between Pituitary dependent Cushing’s disease and Ectopic ACTH syndrome
121
If raised cortisol levels are suppressed by 50% or more, by high dose dexamethasone, what is the diagnosis?
Pituitary dependent Cushing’s disease
122
What is a normal GFR?
120 ml/min
| Age-relaqted decline ~1 ml/min per year
123
What is the gold standard measurement of GFR?
Inulin clearance - required steady state infusion, research tool only
124
Factors which limit the use of serum creatinine as a marker of GFR?
Related to muscle mass
Actively secreted into urine by tubular cells causes overestimation
Generation differs with age, sex, race
125
Equations used to refine endogenous markers
Cockcroft Gault - estimates creatinine clearance (not GFR)
| MDRD - estimates GFR but may underestimate if above-average weight and young
126
Calcium oxalate crystals in the urine can be caused by what?
- most common constituent of human kidney stones
| - one of the toxic effects of ethylene glycol poisoning
127
What are muddy brown casts in the urine a sign of?
Acute tubular necrosis
128
What are red blood cell casts strongly indicative of?
Glomerular damage and haemorrhage.
129
You admit a 28 year old man who you suspect has a renal stone, what is your first choice of imaging?
CT
130
What is the hallmark of pre-renal acute kidney injury?
Reduced renal perfusion (generalised hypotension or selective renal ischaemia)
No structural abnormality
131
Causes of pre-renal AKI?
- True volume depletion
- Hypotension
- Oedematous states
- Selective renal ischaemia - RAS
- Drugs affecting glomerular blood flow (NSAIDs, ACEI, Diuretics, Calcineurin inhibitors)
132
How do NSAIDs and Calcineurin inhibitors precipitate pre-renal AKI?
Decrease afferent arteriolar dilatation
133
How do ACEI or ARBs precipitate pre-renal AKI?
Decrease efferent arteriolar constriction
134
How do pre-renal AKI and acute tubular necrosis differ?
Pre-Renal AKI is not associated with structural renal damage and responds immediately to restoration of circulating volume where as ATN does not respond.
135
What is the hallmark of post-renal acute kidney injury? Examples?
Physical obstruction to urine flow
- (Intra-renal obstruction)
- Ureteric obstruction (bilateral)
- Prostatic / Urethral obstruction
- Blocked urinary catheter
136
What occurs with prolonged obstructive uropathy?
Glomerular ischaemia
Tubular damage
Long term interstitial scarring
137
What groups of intrinsic renal disease are there?
Vascular
Glomerular
Tubular
Interstitial
138
What are there causes of acute renal injury with direct tubular injury?
```
Most commonly ischaemic
Endogenous toxins - myoglobin, immunoglobulins
Exogenous toxins - contrast, drugs
- Aminoglycosides
- Amphotericin
- Acyclovir
```
139
What system is used to help stage acute kidney injury?
```
RIFLE classification
(risk, injury, failure, loss, ESRD)
```
140
How is stage 5 chronic kidney disease defined?
End-stage renal disease
| GFR < 15 or on dialysis
141
How is stage 1 chronic kidney disease defined?
Kidney damage with normal GFR > 90
142
Common causes of chronic kidney disease
- Diabetes
- Atherosclerotic renal disease
- Hypertension
- Chronic Glomerulonephritis
- Infective or obstructive uropathy
- Polycystic kidney disease
143
What are the consequences of chronic kidney disease?
```
1]Progressive failure of homeostatic function
-Acidosis -Hyperkalaemia
2]Progressive failure of hormonal function
-Anaemia -Renal Bone Disease
3]Cardiovascular disease
-Vascular calcification
-Uraemic cardiomyopathy
4]Uraemia and Death
```
144
How does CKD affect the acid-base status and how is it managed?
Metabolic acidosis due to failure of renal excretion of protons
Treated by oral sodium bicarbonate
145
What is a major cause of hyperkalaemia in patients with CKD?
Dietary intake and drugs (ACEI, Spironolactone)
| High potassium levels are found in foods such as milk, chocolate, dried fruits and tomatoes.
146
What ECG changes can be observed with hyperkalaemia?
- Tall peaked T waves
- Loss/flattening of P wave
- Widened QRS complex
147
What type of anaemia is caused by CKD?
Normochromic, normocytic anaemia
Due to progressive decline in erythropoietin-producing cells with loss of renal parenchyma.
Usually noted when GFR<30
148
How does CKD affect the bones?
Renal bone disease - reduced bone density, bone pain, fractures:
- Osteitis fibrosa
- Osteomalacia
- Adynamic bone disease
- Mixed osteodystrophy
149
What is the underlying problem with osteitis fibrosa?
Hyper-parathyroidism
| Causes osteoclastic resorption of calcified bone and replacement by fibrous tissue
150
What can drug directly suppresses PTH?
Cinacalcet
151
How can renal bone disease be treated?
```
Phosphate control
-Dietary
-Phosphate binders
Vit D receptor activators
-1alpha calcidol
-Paricalcitol
Direct PTH suppression
-Cinacalcet
```
152
How do renal vascular lesions differ from traditional atheroma?
Renal vascular lesions are frequently characterised by heavily calcified plaques, rather than traditional lipid-rich atheroma.
153
Which hormones are involved in renal regulation of potassium?
Angiotensin II
| Aldosterone
154
What is a normal serum concentration of potassium?
3.5-5.0 mmol/L
155
Which cells does aldosterone act on?
Principal cells of the cortical collecting tubule
156
What effect does aldosterone have on kidney cells?
Aldosterone increases no. open Na+ channels in the luminal membrane, increasing Na+ reabsorption and hence K+ secretion
157
What are the stimuli for aldosterone secretion?
Angiotensin II
| Potassium
158
What are the main causes of hyperkalaemia?
- Renal impairment: reduced renal excretion
- Drugs: ACE inhibitors, ARBs, spironolactone
- Low Aldosterone: Addison’s disease, Type 4 renal tubular acidosis (low renin, low aldosterone)
- Release from cells: rhabdomyloysis, acidosis
159
How would you manage a patient with hyperkalaemia?
- 10 ml 10% calcium gluconate
- 50 ml 50% dextrose + 10 units of insulin
- Nebulized salbutamol
- Treat the underlying cause
160
What are the causes of hypokalaemia?
- GI loss
- Renal loss: hyperaldosteronism (excess cortisol), increased sodium delivery to distal nephron, osmotic diuresis
- Redistribution into the cells: insulin, beta-agonists, alkalosis
- Rare causes: Renal tubular acidosis type 1& 2, hypomagnesaemia
161
What are the clinical features hypokalaemia?
Muscle Weakness
Cardiac arrhythmia
Polyuria & polydipsia (nephrogenic DI)
162
What screening test would you order in a patient with hypokalaemia and hypertension?
Aldosterone: Renin ratio
163
How would you manage a patient with a serum potassium 3.0-3.5 mmol/L?
- Oral potassium chloride (two SandoK tablets tds for 48 hrs)
- Recheck serum potassium
- Treat the underlying cause e.g. spironolactone
164
How would you manage a patient with a serum potassium < 3.0 mmol/L?
- IV potassium chloride
- Maximum rate 10 mmol per hour
- Rates > 20 mmol per hour are highly irritating to peripheral veins
- Treat the underlying cause e.g. spironolactone
165
What is a normal WBC ?
4.0-11.0
166
What is a normal platelet count?
150-400
167
What is a normal serum Na concentration?
135-145
168
What is a normal serum urea concentration?
3.5-7.0
169
What is a normal serum creatinine concentration?
70-120
170
What hormones are produced by the anterior pituitary?
GH, prolactin, TSH, LH, FSH, ACTH, MSH
171
How can the function of the anterior pituitary be tested?
Combined pituitary function test aka triple test - inject insulin, GnRH and TRH, causing hypoglycaemia (<2.2). Measure hormones and cortisol.
172
Does pituitary failure cause hypotension?
No!
173
How is prolactin secretion controlled in the pituitary?
Dopamine inhibits prolactin secretion, whereas TRH stimulates prolactin secretion as well as stimulating TSH secretion, hence hypothyroidism can also cause secondary hyperprolactinaemia
174
What level of prolactin is indicative of a prolactinoma?
>6000
175
In panhypopituitarism/pituitary failure, what hormone needs urgent replacement?
Hydrocortisone replacement.
| Additionally/later Thyroxine, Oestrogen and GH replacement and a dopamine agonist: bromocriptine or cabergoline
176
In addition to Hydrocortisone, Thyroxine, Oestrogen and GH replacement, what does a patient with a non-functioning pituitary adenoma need?
A dopamine agonist: bromocriptine or cabergoline. Won't shrink the tumour like it would with a prolactinoma but will reduce prolactin levels
177
What dynamic test should be done for a patient with suspected acromegaly?
Glucose tolerance test
| Also can measure IGF-1 levels
178
What is the best treatment for acromegaly?
Pituitary surgery, followed by;
Pituitary radiotherapy,
Cabergoline,
Octreotide.
179
What is the normal range of total serum Ca?
2.2-2.6 mmol/L
180
How does PTH increase serum Ca concentration?
Increases bone resorption, renal resorption and gut absorption.
181
How do vit D and PTH effect phosphate?
PTH stimulates renal phosphate wasting,
| Vit D stimulates intestinal phosphate absorption
182
What is the commonest cause of hypercalcaemia in the general population?
Primary hyperparathyroidism. In hospital it is malignancy.
183
What is the defect in familial hypocalciuric/benign hypercalcaemia? How can it be distinquishes from primary hyperparathyroidism?
Calcium sensing receptor (CaSR)
| Low urine calcium compared to high in primary hyperparathyroidism.
184
What types of hypercalcaemia are there in malignancy?
- Humoral hypercalcaemia of malignancy (eg small cell lung Ca) PTHrP
- Bone metastases (eg breast Ca): Local bone osteolysis
- Haematological malignancy (eg myeloma): cytokines
185
What are the causes of non-PTH driven hypercalcaemia?
- Malignancy
- Sarcoidosis (non-renal 1α hydroxylation)
- Thyrotoxicosis (thyroxine -> bone resorption)
- Hypoadrenalism (renal Ca2+ transport)
- Thiazide diuretics (renal Ca2+ transport)
- Excess vitamin D (eg sunbeds…)
186
What is the acute management for hypercalcaemia?
Fluid resuscitation
Bisphosphonates
Treat underlying cause
187
What are the clinical signs of hypocalcaemia?
```
Trousseau's sign
Chvostek's sign
Hyperreflexia
Laryngeal spasm (stidor)
Convulsions
Prolonged Q-T interval
Choked disk on fundoscopy
```
188
What are the non-PTH driven causes of hypocalcaemia?
i. e. secondary hyperparathyroidism
- Vit D def
- Chronic kidney disease disease (1α hydroxylation)
- PTH resistance (pseudohypoparathyroidism)
189
What are the PTH driven causes of hypocalcaemia?
i. e. lack of PTH
- Surgical (inc post thyroidectomy)
- Auto-immune hypoparathyroidism
- Congenital absence of parathyroids (e.g. DiGeorge syndrome)
- Mg deficiency (PTH regulation)
190
```
A 48 year old woman presents with confusion, back pain and leg weakness.
Adj Ca 3.4 (2.2-2.6)
Phos 1.2 (0.8-1.5)
PTH 0.3 (1.1-6.8)
ALP 400 (30-130)
Diagnosis?
```
Metastatic disease, likely breast. Could be multiple myeloma but usually has a normal ALP and patient is too young.
191
```
A 55 year old man presents with muscle and bone aches. On DEXA scanning he is found to have reduced bone density.
Adj Ca 2.9 (2.2-2.6)
Phos 0.6 (0.8-1.5)
PTH 5.8 (1.1-6.8)
ALP 150 (30-130)
Vit D 55 (70-150)
Diagnosis?
```
Primary hyperparathyroidism, with vit D deficiency. Inappropriately normal PTH with reduced bone density.
192
A 34 year old woman with a history of thyroid carcinoma presents with muscle weakness and paraesthesiae.
Adj Ca 1.6 (2.2-2.6)
Phos 1.4 (0.8-1.5)
PTH
Parathyroidectomy
193
What abnormalities in biochemistry are there with osteoporosis?
None, normally normal.
194
How is osteopenia defined with DEXA scans?
T score between -1 and -2.5
195
What lifestyle modifications can be made to treat osteoporosis?
Encourage weight-bearing exercise
Stop smoking
Reduce alcohol intake
196
What types of drugs are used to treat osteoporosis?
```
Bisphosphonates
Vit D / Ca supplementation
Strontium
SERMs e.g. raloxifene
PTH analogue e.g. teriparatide
HRT - oestrogen
```
197
What does vitamin D deficiency cause in adults?
Osteomalacia
| Children get rickets
198
What malignancy is there an increased risk of with Paget's disease?
Osteosarcoma
199
Risk factors for renal stones?
Dehydration
Abnormal urine pH e.g. meat intake (alkolotic), renal tubular acidosis (acidic)
increased excretion of stone constituents
UTI
Anatomical variants
200
What are the commonest compositions of renal calculi?
```
Calcium - mixed (45%)
Calcium oxalate (35%)
Struvite (10%)
Uric acid (5%)
Cysteine (1-2%)
Calcium phosphate (1%)
```
201
Which type of renal calculi are radio-lucent?
Uric acid and cysteine
202
What composition is a 'staghorn' calculi usually?
Struvite (triple phosphate)
203
What is the Ca level in most patients with renal stones?
Normal
204
Management of calcium renal stones
```
Avoid dehydration
Reduce oxalate intake
Don’t reduce Ca intake (-> bone resorption + increased oxalate excretion)
Thiazides -> hypocalciuric
Citrate (alkalinise urine)
Treat underlying cause
```
205
What is a common cause of struvite renal stones?
Urine infection with urea splitting organism e.g. Klebsiella, proteus etc)
206
What causes cystine stones?
Underlying genetic defect causing cystinuria - often young patient.
207
What are the three most common causes of hypothyroidism?
- Hashimoto's disease
- Atrophic
- Post-graves' disease treatment
208
How can hypothyroidism affect Na+ and RBC levels?
Can cause hyponatraemia and a normocytic anaemia or macrocytic if have pernicious anaemia.
209
Which antibodies may be associated with hypothyroidism?
Anti-Thyroid peroxidase (thyroid microsomal)
210
What are the most common autoimmune conditions which may be associated with thyroid disease?
Pernicious anaemia
Coeliac disease
Addison's disease
211
What test must be done before starting a patient on thyroxine?
E.C.G. to try and identify heart disease.
| Start with low dose and titrate up.
212
What are the side effects of excessive T4 replacement?
Osteopaenia
| Atrial fibrillation
213
How is subclinical hypothyroidism diagnosed?
High TSH but normal T4 - compensated hypothyroidism.
Test for anti-TPO antibodies to predict progression.
Associated with hypercholestrolaemia, only treat if raised.
214
What happens to the free T4 level in pregnancy?
It increases in response to hCG, TSH goes down, TBG increases lots.
215
What is sick euthyroid syndrome?
In response to any severe illness, the pituitary thyroid axis in altered to reduce T4 levels with a normal TSH. No clinical features of hypothyroidism.
216
What are the three most common causes of hyperthyroidism?
Graves' disease 40-60%
Toxic multinodular goitre 30-50%
Single toxic adenoma 5%
Will have high update on technitium scan
217
What causes of hyperthyroidism will have a low uptake on technitium scan?
Subacute thyroiditis
| Postpartum thyroiditis
218
What are the treatment options for graves' disease?
Radioactive Iodine 131 (not if eye disease)
Carbimazole
Propylthiouracil
- Titrate or block and replace
219
What types of thyroid cancer are there?
Papillary
Follicular
Medullary carcinoma (C cells) - can be part of MEN type II
220
What can be used as a tumour marker to monitor recurrence of thyroid cancer?
Thyroglobulin
221
What tumour markers can be measured for medullary carcinoma of the thyroid?
```
Calcitonin
Carcinoembryonic antigen (CEA)
```
222
What are the fat soluble vitamins?
A retinol
D cholecaliferol
E Tocopherol
K Phytomenadione
223
What problems can there be with vit A?
Deficiency - colour blindness
| Excess - Exfoliation, Hepatitis
224
What problems can there be with vit D?
Deficiency - Osteomalacia / Rickets
| Excess - Hypercalcaemia
225
What problems can there be with vit E?
Deficiency - Anaemia / neuropathy / malignancy / IHD
226
What problems can a deficiency in B1 cause and how is it tested?
Thiamin deficiency can cause Beri-Beri, Neuropathy, Wernicke Syndrome.
Test RBC transketolase
227
What problems can a deficiency in B2 cause and how is it tested?
Riboflavin deficiency can cause glossitis.
| Test RBC glutathione reductase
228
What problems can a deficiency or excess of B6 cause and how is it tested?
Pyridoxine deficiency can causes dermatitis, anaemia. Excess - neuropathy
Test RBC AST activation
229
What problems can a deficiency in B12 cause and how is it tested?
Cobalamin deficiency can cause pernicious anaemia
| Test serum B12 levels
230
What problems can a deficiency or excess of Vit C cause and how is it tested?
Deficiency - scurvy
Excess - renal stones
Test - plasma levels
231
What problems can a deficiency in folate cause and how is it tested?
Megaloblastic anaemia, Neural tube defects
| Test - RBC folate
232
What problems can a deficiency in B3 cause?
Niacin deficiency can cause Pellagra - Diarrhoea, Dementia, Dermatitis.
233
What can be caused by a deficiency in zinc, copper or fluoride?
Zinc - dermatitis
Copper - anaemia
Fluoride - dental caries
234
What main hormones are produced by white adipose tissue?
Leptin
| Adiponectin (low levels linked to insulin resistance)
235
What is the recommended protein intake per day for men and women?
Men 84 gm
| Women 64 gm
236
What types of fatty acids are better for you?
Polyunsaturated better than saturated
| Cis-monosaturates better than trans-monosaturates
237
What are the characteristics of metabolic syndrome?
- Fasting glucose >6.0 mmol/L
- HDL Men 135/80
- Waist circumference men >102 women >88
- Microalbumin, insulin resistance
238
What endocrine disorders should be excluded with an obese patient?
Cushings and acromegaly
239
What is the normal range of blood pH?
7.45 - 7.35
240
What is the main buffer system present in different regions of the body?
Bicarbonate - ECF + glomerular filtrate
Haemoglobin - RBCs
Phosphate - renal tubular fluid + intracelluar
Also protein and bone
241
What are the main causes of a metabolic acidosis?
- increased H+ production e.g. diabetic ketoacidosis, lactic acidosis
- decreased H+ excretion e.g. renal failure
- loss of bicarbonate e.g. fistula
242
What are the different plasma lipoproteins, in size order?
Largest: Chylomicrons
VLDL - main triglyceride carrier ~55%
LDL - main cholesterol carrier ~70%
Smallest: HCL
243
What mutations can cause familial hypercholesterolaemia (type II)?
Dominant mutations of LDL receptor, apoB or PCSK9 genes.
| Rarely, autosomal recessive mutation of LDLRAP1
244
What are the mutations in phytosterolaemia?
mutations of ATP-binding cassette (ABC) transporters G5 and G8 - allow gut to absorb plant sterols
245
What are the commonest causes of primary hypercholesterolaemia ?
- Familial hypercholesterolaemia
- Polygenic hypercholesterolaemia
- Familial hyper-alpha-lipoproteinaemia
- Phytosterolaemia
- cholesterol ester storage disease
- cerebro-tendinous xanthomatosis
246
What are the different types of familial hyperlipidemias and what mutations are associated with them?
Type I - lipoprotein lipase or apoC II
Type II aka Familial hypercholesterolemia - LDLR, apoB, PCSK9
Type III - apoE2
Type IV aka Familial hypertriglyceridemia
Type V - ?
247
What is pathognomonic of familial hyperlipidemia type III?
Palmar striae - yellow/xanthomatous palmar crease.
248
What are the causes of secondary hyperlipidaemia?
Hormonal influences: pregnancy, exogenous sex hormones or hypothyroidism
Metabolic disorders: diabetes and obesity
Renal dysfunction
Obstructive liver disease
Beverages: alcohol and coffee
Iatrogenic: cyclosporin, amiodarone, retinoids and anti-retroviral drugs
249
What are the causes of primary hypolipoproteinaemia?
- A-beta-lipoproteinaemia: recessively inherited mutations of microsomal triglyceride transport protein (MTP);
- Familial hypo-beta-lipoproteinaemia: dominantly inherited mutations of the apoB gene;
- Tangier disease (HDL def): homozygosity for mutations of ABCA1;
- Familial hypoalphalipoproteinaemia, heterozygous inheritance of mutations of either ABCA1 or of apoA-1.
250
What is the best biochemical predictor of CHD risk?
Total:HDL cholesterol ratio, which reflects the opposing influences of atherogenic VLDL and LDL versus anti-atherogenic HDL.
251
What lipid-lowering drugs are there?
HMG CoA reductase inhibitor (statins)
Bile acid sequestrants (eg colestryramine)
In deveopment: MTP-inhibitors, anti-sense apoB oligonucleotides and anti-PCSK9 monoclonal antibodies.
252
What treatment is used to treat severe, statin-refractory forms of dyslipidaemia?
Lipoprotein apheresis
253
How is a successful outcome from bariatric surgery defined?
>50% loss in excess body weight (actual – ideal) and accompanied by marked decreases in diabetes, serum triglycerides, fatty liver and hypertension.
254
What drugs are used to raise HDL levels?
CETP inhibitors and apoA1 and HDL-mimetic compounds.
255
What is uric acid?
The end product of purine metabolism.
256
How is urate excreted?
1/3 secreted into the gut - degraded by bacterial uricase
| 2/3 renal excretion - 90% reabsorbed in PCT
257
What are the primary causes of urate overproduction?
PRPS overactivity (denovo synthesis) or HGPRT deficiency (salvage pathway)
258
What are the secondary causes of urate overproduction?
- increased dietary purine intake
- increased nucleotide turnover (psoriasis, myeolo- or lymphoproliferative diseases)
- increased ATP metabolism
- drugs e.g. cytotoxics
259
What are the causes of urate under-excretion?
- Primary hyperuricaemia - defect in PCT transporters (increased resorption)
- Impaired renal function
- Inhibition of urate secretion (acidosis)
- Drugs
260
What are the effects of high uric acid?
- Gout
- Renal calculi
- Tophi
- Acute urate nephropathy - widespread crystallisation in renal tubules
261
What crystals precipitate from high uric acid and at what level?
Monosodium urate crystals
| [urate] > 0.38 mmol/L
262
What is acute and chronic gout called?
Podagra - big toe
| Tophaceous gout - chronic
263
What are the risk factors for gout?
```
Hyperuricaemia
Family history
Obesity
Alcohol
Hypertension
Renal impairment
Drugs (diuretics, salicylates (low dose), tacrolimus, ciclosporin, cytotoxics)
```
264
What is the treatment for an acute gout attack?
NSAIDs
Colchicine
Glucocoticoids
265
For which patients is urate lowering therapy indicated and with what treatment?
Patients with recurrent gout attacks, chronic arthropathy, tophi and gout with uric acid stones.
Allopurinol reduces synthesis
Probenecid increases renal excretion
266
How does allopurinol work?
Xanthene oxidase inhibitor - blocks uric acid production
267
What do gout and pseudogout crystals look like under polarised light?
Monosodium urate - yellow, negatively birefringent
| Calcium pyrophosphate - blue, positively birefringent
268
What is Lesch Nyhan syndrome?
X-linked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT - salvage pathway)
- normal at birth, dev delay 6/12
- hyperuricaemia
- choreiform movements (1 yr)
- spasticity, mental retardation, self mutilation (85%)
269
Which tissues make alkaline phosphatase?
Bone, liver, intestines, placenta.
270
How can the source of increased serum enzymes be localised to specific tissues?
1 - measurement of more than one enzyme e.g. GGT can be used to localise ALP to liver
2 - Separation and measurement of tissue- specific isoenzymes e.g. bone and liver ALP
271
What pathological causes are there for a raised ALP?
> 5x Upper limit of normal
- Bone ( Pagets, Osteomalacia)
- Liver ( cholestasis, cirrhosis)
< 5x Upper Limit Normal
- Bone ( tumours, fractures, osteomyelitis)
- Liver (infiltrative disease,hepatitis)
NOT osteoporosis unless complicated by fractures
272
What forms of creatine kinase are there?
CK-MM- skeletal muscles
CK-MB (1 & 2) – cardiac muscles
CK-BB – brain – activity minimal even in severe brain damage
273
What is the time line for troponin following a MI? When should it be measured clinically?
Rise 4-6 hours post MI, peak at 12-24 hours, remains elevated for 3-10 days.
Measure at 6 and 12 hrs post onset of chest pain.
274
What biomarkers can be measured in heart failure?
Atrial and brain natriuretic peptides (secreted by atria and ventricles, respectively)
BNP can be measured to assess ventricular function - if normal, unlikely to have heart failure, used to exclude.
275
Define 1 international unit (U) of enzyme activity.
- 1 International Unit (U) of enzyme activity is defined as the quantity of enzyme that catalyses the reaction of one μmol of substrate per minute.
- Activity of an enzyme is dependent on assay conditions such as temperature, pH.
276
What is the action of ADH (vasopresin)?
- Acts of V2 receptors on renal tubular cells in collecting duct resulting in aquaporin-2 water channels being inserted into the tubular membrane - increases water resorption.
- At high conc binds to V1 receptors on vascular smooth muscle causing vasoconstriction
277
What are the two main stimuli for ADH secretion?
- Serum osmolality (mediated by hypothalamic osmoreceptors)
| - Blood volume/pressure (mediated by baroreceptors in carotids, atria, aorta)
278
What are the causes of hyponatraemia in a hypovolaemic patient?
- Renal cause of volume depletion e.g. diuretics, salt-losing nephropathy
- Extra-renal cause of volume depletion e.g. diarrhoea, vomiting
279
What are the causes of hyponatraemia in a hypervolaemic patient?
- Cardiac failure
- Cirrhosis
- Renal failure
280
What are the causes of hyponatraemia in a euvolaemic patient?
- Hypothyroidism
- Adrenal insufficiency
- Syndrome of inappropriate ADH (SIADH)
281
What are the causes of Syndrome of Inappropriate ADH secretion (SIADH)?
- CNS pathology
- Lung pathology
- Drugs (SSRI, TCA, opiates, PPIs, carbamazepine)
- Tumours
282
What investigations would you order in a patient with euvolaemic hyponatraemia?
? Hypothyroidism: Thyroid function tests
? Adrenal insufficiency: Short Synacthen test
? SIADH: Plasma & urine osmolality (low plasma & high urine osmolality)
283
How would you manage a hypovolaemic patient with hyponatraemia?
Volume replacement with 0.9% saline
284
How would you manage a hypervolaemic patient with hyponatraemia?
```
Fluid restriction (total fluid <500ml)
Treat the underlying cause
```
285
How would you manage a euvolaemic patient with hyponatraemia?
```
Fluid restriction (total fluid <500ml)
Treat the underlying cause
```
286
What is the most important point to remember while correcting hyponatraemia?
- Serum Na must NOT be corrected > 10 mmol/L in the first 24 hours
- Risk of osmotic demyelination: central pontine myelionlysis (quadriplegia, pseudobulbar palsy, seizures, coma, death)
287
If water restriction is insufficient to treat SIADH, what drugs can be used?
- Demeclocycline: Reduces responsiveness of collecting tubule cells to ADH. Monitor U&Es (risk of nephrotoxicity)
- Tolvaptan: V2 receptor antagonist
288
What are the main causes of hypernatraemia?
- Unreplaced water loss:
Gastrointestinal losses
Renal losses: osmotic diuresis, reduced ADH release/action (Diabetes insipidus)
- Patient cannot control water intake e.g. children, elderly
289
What investigations would you order in a patient with suspected diabetes insipidus?
Water deprivation test
290
How would you treat hypernatraemia?
Fluid replacement
- Correct water deficit (5% dextrose)
- Correct volume depletion (0.9% saline)
Treat the underlying cause
291
How do neonatal kidneys differ to adult ones?
1 - Neonatal GFR is low
2 - Proximal tubules are short and less convoluted
3 - The distal tubules are relatively unresponsive to aldosterone
4 - The loops of Henle/distal collecting ducts are short
5 - Renal function does not fully mature until ~2 years
292
What are the consequences of a low GFR in neonates?
Slow excretion of a solute load
| Limited amount of Na+ available for H+ exchange - suseptible to acidosis
293
What are the consequences of short and less convoluted proximal tubules in neonates?
There is a lower reabsorptove capability but it is usually adequate for the small filtered load.
Threshold for glycosuria lower
294
What are the consequences of short loops of Henle/distal collecting ducts in neonates?
They have a reduced concentrating ability with a maximum urine osmolality of 700 mmol/kg
295
What are the consequences of distal tubule unresponsiveness to aldosterone in neonates?
Leads to a persistent loss of Na and hence a reduced potential potassium excretion: higher ULN 6.0 mmol/L
296
What are the commonest causes of a conjugated hyperbilirubinaemia in neonates?
- Biliary atresia
- Choledocal cyst
- Ascending cholangitis: associated with lipid content of TPN
- Inherited metabolic diseases (Alpha-1-antitrypsin deficiency, Tyrosinaemia type I,Galactosaemias, Peroxisomal disorders)
297
What are the causes of a unconjugated hyperbilirubinaemia in neonates?
```
Haemolytic
- Haemolytic disease (ABO, rhesus etc)
- G-6-PD deficiency
Non-haemolytic
- Feeding problems
- Breast milk jaundice
- Prenatal infection/sepsis, hepatitis
- Hypothyroidism
- Crigler-Najjar type I
```
