Chemical Pathology Flashcards
1
Q
Which cycle forms ammonia?
A
Urea cycle
2
Q
Name three urea cycle defects:
A
- Lysinuric protein intolerance
- Hyperornithinaemia-Hyperammonaemia-Homocitrullinuria (HHH)
- Citrullinemia type III.
3
Q
What is the inheritance pattern of Ornithine Transcarboxylase Deficiency?
A
X-linked
4
Q
What serum marker is a marker of hyperammoniaemia?
A
Serum glutamine
5
Q
What urine marker is a marker of hyperammoniaemia?
A
Urine orotic acid
6
Q
What is the first line management for hyperammoniaemia?
A
Sodium benzoate
7
Q
Which acid-base disorder is associated with raised ammonia?
A
Respiratory alkalosis
8
Q
Why is hyperammoniaemia associated with respiratory alkalosis?
A
Induces hyperventilation of the central respiratory drive
9
Q
What are the features of a urea cycle disorder?
A
- Vomiting without diarrhoea
- Respiratory alkalosis – Hyperammonaemia induces hyperventilation of the central respiratory drive.
- Neurological encephalopathy
- Avoidance or change in diet.
- Hyperammonaemia - >200 uM.
10
Q
Name a common organic aciduria
A
Isovaleric Acidaemia
11
Q
What type of smell is associated with Isovaleric Acidaemia (urine)
A
Cheesy or sweaty smell
12
Q
How is leucine exported from the cell?
A
Isovaleryl carnitine
13
Q
What is the neonatal presentation of an organic aciduria?
A
- Unusual odour
- Truncal hypotonia
- Hypocalcaemia
- Pancytopenia
- Lethargy
- Limb hypertonia
- Neutropenia
- Feeding problems
- Myoclonic jerks
14
Q
What is the trigger of Reye’s syndrome?
A
salicylates (aspirin)
15
Q
What is the presentation of Reye’s syndrome?
A
- Vomiting, lethargy
- Increasing confusion, seizures
- Decerebration
- Respiratory arrest
16
Q
When is the Guthrie spot test performed?
A
At 5-6 days ofa ge
17
Q
What five conditions are screened in the Guthrie spot test?
A
Phenylketonuria
Congenital hypothyroidism
Cystic fibrosis
Sickle cell anaemia
MCAD deficiency
18
Q
Which enzyme is deficiency in phenylketonuria?
A
Phenylalanine hydroxylase
19
Q
How is phenylketonuria screened
A
Phenylalanine levels
20
Q
How is congenital hypothyroidism screened?
A
TSH levels
21
Q
What is the commonest mutation associated with cystic fibrosis?
A
F508del CFTR
22
Q
Which test is used to screen for cystic fibrosis at 5 days of age?
A
Immune reactive trypsin
23
Q
What screening test is performed for diagnosing MCAD?
A
Acylcarnitine
24
Q
PAH converts phenylalanine into what?
A
Tyrosine
24
Phenylketonuria results in an accumulation of what?
phenylalanine
25
What are the clinical features associated with phenylketonuria?
Low IQ <50
Delayed developmental milestones, microcephaly, hypopigmentation, hyperactivity, seizures and musty odour to skin and urine
26
What is the chronic management for phenylketonuria?
Low Phe and adequate tyrosine intake
27
What is the consequence of mitochondrial fatty-acid beta oxidation?
Hypoketotic hypoglycaemia
+ hepatomegaly and cardiomegaly
28
What are the three types of ketones?
Acetone, acetoacetate, 3-hydroxybutryate.
29
Galactosaemia is characterised by a deficiency of which enzyme?
galactose-1-phosphate uridyl transferase (GALT)
30
Galactosaemia is characterised by what raised serum marker?
Raised Gal-1 phosphate and galactose
31
Gal-1-phosphate is a substrate for which ocular molecule?
Aldolase
32
High concentrations of Gal-1-phosphate can result in what ocular complications?
Bilateral cataracts
33
What is the investigation of choice for diagnosing galactosaemia?
* Urinary galactose
34
Management of galactosaemia?
Avoid galactose sources e.g., milk
35
Type 1 glycogen-storage disease is associated with which enzyme deficiency?
Glucose-6-phosphatase
36
What is the clinical presentation of glycogen storage disease?
* Hypoglycaemia
* Hepatomegaly
* Lactic acidosis
* Exercise intolerance
* Protruding abdomen
* Faltering growth, growth failure, short stature, and thin legs
* Weakness
* Neutropenia – Recurrent bacterial infection in GSD1b (Impaired neutrophil homeostasis).
37
GSD1 causes what type of hypoglycaemia?
Hypoketotic due to inhibition of fatty acid oxidation by malonic acid
38
What is the the management of GSD type 1?
Nocturnal intragastric glucose feedings during the first 2 years of life, and appropriate carbohydrate intake to maintain satisfactory blood glucose.
39
What is Von Gierke Disease
Glycogen storage disease type 1
40
What is the underlying pathogenesis of GSD-type 1?
Absence of phosphatase – G6P and G1P cannot be exported (phosphate cannot across cell membrane).
* Glucose-6-phosphate transport and hydrolysis requires a catalytic hydrolase – GSD is marked by G6Pase deficiency.
* Leads to progressive glycogen accumulation in the liver, and fasting hypoglycaemia due to impaired export.
41
What is the inheritance pattern for GSD-TYPE 1?
Autosomal recessive
42
What is the inheritance pattern of MCAD?
Autosomal recessive disorder affecting mitochondria fatty acid beta-oxidation
43
MCAD converts medium-chain fatty acyl-CoA into what two products?
short-chain fatty acyl-CoA and acetylCoA
44
What pathway does medium-chain acyl-CoA dehydrogenase play in during the fasting state?
Ketogenesis
45
What type of hypoglycaemia is caused by MCAD?
Hypoketotic hypoglycaemia.
46
When are symptoms of MCAD deficiency evident?
neonatal period between 3 and 15 months after a period of fasting or acute illness
47
How is MCAD deficiency detected on newborn blood screening?
Elevated acylcarnitine
48
Which genetic test confirms the diagnosis of MCAD deficiency?
Homozygous 985A
49
What is the management for MCAD deficiency?
Reducing times of fasting and ensuring nutrition intake to meet metabolic demands + high carbohydrate diet.
50
Zellweger spectrum disorder is associated with an absence or reduction of what?
Functional peroxisomes
51
Which gene is implicated in Zellweger Spectrum Disorder?
PEX gene
52
What is the neonatal presentation of Zellweger Spectrum Disorder ?
* Hypotonia (floppy baby)
- Reduced spontaneous movements and weak cry.
- Feeding difficulty
- Seizure
* Craniofacial abnormalities – facial dysmorphisms, large fontanelles, wide sutures, hypoplastic supraorbital ridges.
* Retinopathy – early blindness.
* Sensorineural deafness
53
Which type of disorders cause nipple inversion and retardation?
Glycosylation disorders
54
Tay-Sachs disease is caused by a deficiency of what enzyme?
hexosaminidase-A
55
Which ethnicity is associated with Tay-Sacs disease?
Ashkenazi Jewish Heritage
56
What is the inheritance pattern for Tay-Sachs disease?
Autosomal recessive
57
What characteristic retinal finding is seen in Tay-Sachs disease?
Cherry red spot
58
What is the clinical presentation of Tay-Sachs disease?
A degenerative disease of grey matter in infancy – symptoms arise between 3-6 months (very slow progressing).
* Mild motor weakness
* Irritability
* Hypersensitivity to auditory and sensory stimuli
* Exaggerated startle response (auditory myoclonus)
* Neuroregression.
* Hepatosplenomegaly
* Cardiomyopathy
59
What is the investigation performed for Tay-sachs disease?
Urine mucolipopolysaccharides and WBC enzyme levels.
60
What is the management for Tay-Sachs disease?
Enzyme replacement therapy; substrate reduction therapy, and bone marrow transplantation.
61
What is the 60-40-20 rule regarding the distribution of water?
60% - total body weight
40% - intracellular
20% extracellular
62
Concentrations of sodium and chloride are raised in which compartment?
Extracellular
63
What term denotes the total number of particles in solution?
Osmolality
64
What is the units for osmolality?
mmol/Kg
65
What are the unites for osmolarity?
mmol/L
66
What are the physiological determinants of osmolality?
Na+ + K+ + HCO3- + Urea + Glucose.
67
What is the calculation for osmolarity?
2 (Na+ + K+) + urea and glucose.
68
What is the normal range for osmolality?
275 – 295 mmol/kg.
69
if the osmolarity < osmolality, what should be assumed?
There are additional unmeasured solutes that are dissolved in the serum
70
What is the normal range of sodium?
135-145 mmol/L
71
What is the threshold for severe hyponatraemia?
<125 mmol/L
72
What are the clinical presentations of symptomatic hyponatraemia?
o Nausea and vomiting (<134 mmol/L)
o Confusion (<131 mmol/L)
o Seizures, non-cardiogenic pulmonary oedema (<125 mmol/L)
o Coma (<117 mmol/L) and eventual death.
73
What are the causes of high osmolality?
Glucose/mannitol infusion
74
What term describes hyponatraemia caused by irrigation absorbed through damaged prostate?
TURP syndrome
75
What is the osmolality associated with pseudohyponatraemia?
Normal/high
76
What are the three classifications of true hyponatraemia?
Hypervolaemia
Euvolaemic
Hypovolaemic
77
What are the renal hypovolaemic causes of hyponatraemia?
Diuretics, Addison's, salt-losing nephropathies
78
How can hyponatraemia be distinguished?
By hydration status and urinary Na+
79
What determines renal versus non-renal causes of hyponatraemia?
Urinary sodium >20 = renal cause
80
what are the non-renal causes of hypovolaemic hyponatraemia?
Vomiting, diarrhoea, excess sweating, third space losses (ascites, burns)
81
What are the evuolaemic causes of hyponatraemia?
SIADH
Severe hypothyroidism
Glucocorticoid deficiency
82
What are the hypervolaemic causes of true hyponatraemia?
AKI,CKD, cardiac failure, cirrhosis, inappropriate iv fluid
83
Which CAH is associated with salt-loss?
21-hydroxylase deficiency
84
21-hydroxylase deficiency is associated with a reduction in which two hormones?
Cortisol and aldosterone
85
21-hydroxylase deficiency causes an accumulation of what?
17-OH-progesterone
86
What are the clinical features associated with true hyponatraemia?
o Hyponatremia/hyperkalaemia with volume depletion (lack of aldosterone) Salt-losing crisis.
o Hypoglycaemia (lack of cortisol)
o Ambiguous genital in female neonates
o Growth acceleration
87
Why is cirrhosis associated with hyponatraemai?
Liver failure causes an impaired breakdown of vasodilators (nitric oxide) - low BP causes a rise in ADH - water retention - dilutional effect on sodium
88
Which marker is raised in heart failure and exacerbates hyponatraemia?
ADH
89
What is the management for hypovolaemic hyponatraemia?
Manage cause - e.g., anti-emetics
Replace depleted fluid with regular sodium monitoring
90
How is Addison's managed?
Hydrocortisone +/- Fludrocortisone.
91
What is the first-line drug for status epilepticus secondary to hyponatraemia?
Hypertonic saline
92
What is the consequence associated with rapid correction of sodium?
Central pontine myelinolysis
93
What is the presentation of central pontine myelinolysis?
pseudobulbar palsy, paraparesis, locked-in syndrom
94
What is the diagnostic criteria for SIADH?
* True hyponatraemia (<135) + low plasma/serum osmolality (<270) +high urine sodium (>20) + high urine osmolality (>100) + no adrenal/thyroid/renal dysfunction.
* Clinically euvolemic.
95
Which test confirms SIADH?
* Normal 9am cortisol and normal TFTs (I.E diagnosis of exclusion).
96
Which malignancy is associated with SIADH?
Small cell lung cancer (most common); prostate, pancreas, lymphoma (ectopic secretion)
97
Which drugs can cause SIADH?
Opiates, SSRIs, TCAs, carbamazepine, PPIs.
98
what is the management for siadh?
Fluid restriction and manage the cause
99
Which drug can be used to increase ADH resistance for the management of SIADH?
* Demeclocycline and tolvaptan
100
What is the the range threshold for hypernatraemia?
>148 mmol/L
101
What is the presentation of hypernatraemia?
* Sensation of thirst is driven by hypernatremia – self-correction of sodium.
* Thirst Confusion Seizures + ataxia Coma
102
What are hypovolaemic causes of hypernatraemai?
* Loop diuretics
* Osmotic diuresis (uncontrolled DM, glucose, mannitol), following initial hyponatraemia.
* Diabetes insipidus
* Renal disease (impaired concentrating ability).
103
Which endocrine disorder is associated with hypernatraemia?
Conns's syndrome
104
Which electrolyte imbalance is associated with Diabetes insipidus?
Hypernatraemia
105
What is the management for cranial diabetes insipidus?
Desmopressin
106
Cranial diabetes insipidus is caused by what?
Surgery, trauma, tumours (craniopharyngioma), autoimmune hypophysitis (from CTLA-4 ipilimumab).
107
What is the diagnostic investigation for diabetes insipidus?
8-hour water deprivation test
108
What type of diabetes insipidus is characterised by insensitivity to ADH?
Nephrogenic diabetes insipidus (vasopressin receptor resistance0
109
Following administration of desmopressin, what result is observed on a water deprivation test for cranial diabetes insipidus?
Urine osmolality increases to >600 mOsmol/kg
110
What is the normal range for potassium?
3.5-5.5 mmol/L
111
What is the predominant intracellular ion?
Potassium
112
What is the threshold concentration for hypokalaemia?
<3.5 mmol/L
113
What are the renal loss causes of hypokalaemia?
* Hyperaldosterism (Patient with high BP and low K+); iatrogenic excess of cortisol (increased potassium secretion).
* Increased sodium delivery to the distal nephron (thiazide and loop diuretics).
* Osmotic diuresis
114
What i the management of nephrogenic diabetes insipidus?
Thiazide diuretics
115
Which drugs can cause nephrogenic diabetes insipidus?
Lithium, demeclocyline
116
Which drug can cause hypokalaemia?
Beta-agonists
Insulin
Thiazide and loop diuretics
117
What are the rare renal causes of hypokalaemia?
Renal tubular acidosis type 1 and 2
118
Which acid-base abnormality CAUSEs hypokalaemia?
Metabolic alkalosis
119
Which renal tubular acidosis is characterised by hypokalaemia and acidosis?
Type 1 and type 2
120
Which renal tubular acidosis is characterised by hyperkalaemia and acidosis?
Type 4
121
What is type 4 renal tubular acidosis?
Aldosterone deficiency or resistance (acidosis and hyperkalaemia).
122
What is the management for mild hypokalaemia (3 - 3.5 mmol/L)?
Oral KCl (2 SandoK tablets TDS for 48h)
123
What is the management for severe hypokalaemia (<3 mmol/L)?
IV potassium chloride due to risk of cardiac arrest
124
Which investigation is performed for Conn's syndrome?
Aldosterone : renin ratio - raised
125
What is the important investigation performed in hyperkalaemia?
ECG
126
Which renal tubular acidosis is associated with hyperkalaemia?
Type 4
127
What is the cause of type 4 renal tubular acidosis?
Aldosterone deficiency
128
Which drugs are associated with decreased excretion of potassium?
Potassium-sparing diuretics (Spironolactone), NSAIDs, ACEi, ARBs.
129
What are the ECGA changes associated with hyperkalaemia?
Loss of P waves
Tall-tented T waves
Widened QRS complexes (Broad-complex ventricular tachycardia)
sine wave pattern
130
What are the indications for calcium gluconate administration in hyperkalaemia?
>5.5 with ECG changes or potassium >6.5
131
What is the first line drug management for hyperkalaemia?
10 mL 10% calcium gluconate
132
What is the second-line management for hyperkalaemia following calcium gluconate?
2. 100 mL 20% dextrose and 10 units of short-acting insulin (Actrapid – insulin will drive potassium into the cells and dextrose prevents hypoglycaemia).
133
Which drug is a potassium binding?
Calcium resonium
134
What is the compensatory response with metabolic acidosis?
Hyperventilation
135
What is the anion gap equation?
(Na + K) – (Cl + HCO3)
136
What is the normal anion gap?
14-18 mmol/L
137
What are the causes of a raised anion gap?
* Glycols – ethylene glycol + propylene glycol
* Oxyproline – Chronic paracetamol use
* L – Lactate (sepsis)
* D – Lactate (Short bowel syndrome)
* M – Methanol overdose
* A – Aspirin
* R – Renal failure
* K – Ketoacidosis
138
What is the calculation for osmolar gap?
Osmolality (measured) - osmolarity (calculated)
139
What are the markers of synthetic function?
* Clotting (INR)
* Albumin
* Glucose
140
What is the best marker for acute liver injury?
Prothrombin time
140
What is raised in acute viral hepatitis?
Transaminitis
141
What is the ratio of ALT:AST in EtOH liver disease?
AST:ALT >2
142
What is the ratio of AST:ALT in viral hepatitis?
1:1
143
Which liver marker differentiates liver-associated rise in ALP from bone?
GGT
144
What are the two raised markers associated with cholestatic/obstructive picture of liver disease?
GGT and ALP
145
What are the physiological cause of isolated raised ALP?
Pregnancy (third trimester)
Childhood (growth spurt)
146
What are the pathological causes of raised ALP >5 ULN?
Paget's disease
Osteomalacia
Liver (cholestasis, cirrhosis)
147
Why is ALP normal in myeloma?
Plasma cells suppress osteoblasts
148
What are the causes of low albumin?
Chronic liver disease
Malnutrition
Protein-losing enteropathy
Nephrotic syndrome
Sepsis (third spacing)
149
What are the causes of a raised urea?
Upper GI bleed
Dehydration/AKI
150
What is the average albumin synthesis?
200 mg/kg/day
151
Why is hypoalbuminaemia common in hospitalised patients?
Due to malnutrition and acute illnness
152
Which clotting factors are synthesised by the liver?
Factor V, VII, IX, X, XII and XIII, fibrinogen and prothrombin.
153
What is is the tumour marker associated with hepatocellular carcinoma?
AFP
154
Why does hypoglycaemia arise in acute hepatic injury?
Due to impaired glycogen storage
155
Which enzyme is implicated in vitamin-D hydroxylation in the liver?
25-hydroxylase
156
Which reticuloendothelial cell is implicated in liver function?
Kupffer cell
157
What is the breakdown product of haem?
Bilirubin
158
How is bilirubin excreted by the kidneys?
As urobilinogen
159
How is bilirubin secreted in the faeces?
Stercobilin
160
What are the three main causes of pre-hepatic jaundice?
Haemolytic anaemia
Ineffective erythropoiesis e.g., thalassemia
Congestive cardiac failure
161
Conjugated bilirubin in pre-hepatic jaundice?
Absent
162
What is raised in pre-hepatic jaundice?
Unconjugated BR
163
Urine bilirubin in pre-hepatic jaundice?
Absent
164
Urine colour in pre-hepatic jaundice?
Normal due to Urobilinogen
165
What are the common hepatic causes of hepatic jaundice?
1) Hepatocellular dysfunction (Viral, alcoholic hepatitis)
2) Impaired conjugation/BR excretion, BR uptake (Gilbert Syndrome, Crigler Najjar Syndrome)
166
What type of bilirubin is raised in intra-hepatic jaundice?
Conjugated
Unconjugated
Urobillinogen
167
Why is urine dark in hepatic jaundice?
Dark (Urobilinogen + conjugated BR)
168
Why is urine dark in post-hepatic jaundice?
Dark (Conjugated BR leaks out of hepatocytes)
169
What are the intraluminal causes of post-hepatic jaundice?
(Stones/strictures)
170
What are the luminal causes of post-hepatic jaundice?
(Mass/neoplasm e.g., PBC, PSC).
171
What are the extra-luminal causes for post-hepatic jaundice?
Pancreas
Cholangiocarcinoma
172
What happens to **haptoglobin** in intravascular haemolysis?
Reduced
173
Which markers are raised in haemolysis?
LDH and unconjugated BR
174
What is the neonatal presentation of Crigler-Najjar Syndrome?
Severe jaundice and Kernicterus
175
Which porphyria is characterised by cutaneous symptoms of vesicular and bullous eruptions on sun-exposed skin?
Porphyria cutanea tarda
175
Which enzyme is partially deficient in Gilbert syndrome?
Glucronyl transferase
176
Which enzyme is deficient in porphyria cutanea tarda?
Uroporphyringoen III decarboxylase
177
Which porphyria is characterised by increased skin fragility, hyperpigmentation, scarring, and chronic photosensitivity?
Porphyria cutanea tarda
178
What are the 4 P's (symptoms) for acute intermittent porphyria?
Painful abdomen
Psychosis
Peripheral neuropathy
Port urine
179
Which enzyme is affected for acute intermittent porphyria?
HMB synthase
180
What is the first line management for acute intermittent porphyria?
Haem arginate
181
Which porphyria is associated with acute neurovisceral attacks, and blistering skin?
Hereditary coproporphyria
182
What urinary marker is raised in acute intermittent porphyria?
Urinary PBG, ALA
183
What is the inheritance pattern for acute intermittent porphyria?
Autosomal dominant
184
What term describes normal T3/T4 but raised TSH?
Subclinical hypothyroidism
185
Which antibody is positive for Hashimoto's thyroiditis?
Anti-thyroid peroxidase
186
Which ovarian tumour secretes thyroid hormone?
Struma ovarri (associated with teratoma)
187
Which drugs can induce thyroiditis?
Amiodarone, lithium, interferon alpha
188
What is the cause of factitious thyroiditis?
Levothyroxine (inappropriate use).
189
What is the symptomatic relief for hyperthyroidism?
Beta-blockers e.g., propanolol
190
What is the target for carbimazole?
Competitive inhibitor for TPO enzyme - block thyroid hormone synthesis
191
What drug reduces peripheral tissue conversion of T4 to T3?
Propylthiouracil
192
What are the side effects associated with carbimazole?
Agranulocytosis
193
Which anti-thyroid drug is recommended for the first trimester of pregnancy?
Propylthiouracil
194
Radioactive iodinine therapy destroys which type of cells?
Thyroid follicular cells
195
A hot spot on US, indicates what?
Toxic adenoma
196
A cold spot on thyroid US indicates what?
Low uptake
197
Multifocal hot spots on thyroid ultrasound indicates what?
Multinodular goitre
198
What are the histological characteristics associated with papillary thyroid cancer?
Psammomma bodies and Orphan-Annie Eyes
199
Orphan-Annie Eyes on histology are associated with which type of thyroid cancer?
Papillary thyroid cancer
200
Which is the commonest thyroid cancer and is associated with a very good prognosis?
Papillary thyroid cancer
201
What is the tumour marker for Papillary thyroid cancer?
Thyroglobulin
202
What is the second commonest type of thyroid cancer?
Follicular thyroid carcinoma
203
What is the tumour marker for follicular thyroid carcinoma?
Thyroglobulin
204
Which thyroid cancer is associated with MEN2?
Medullary thyroid carcinoma
205
What is the marker for medullary thyroid carcinoma?
Calcitonin
206
Calcitonin is secreted from which cells?
Parafollicular C cells
207
Which rare type of thyroid cancer has a poor prognosis?
Anaplastic thyroid cancer
208
Which genes are associated with papillary thyroid carcinoma?
RET/PTC
209
How do thyroid cancers appear on a radioiodine scan?
As a cold nodule
210
What is the most common cause of hypothyroidism worldwide?
Iodine deficiency
211
In the developed world, what is the most common cause of hypothyroidism?
Hashimoto's thyroiditis, primary atrophic hypothyroidism
212
What is Riedel's thyroiditis?
Dense fibrosis, replacing normal parenchyma, painless and sgtony hard
213
What are the common causes of central hypothyroidism?
Pituitary tumours, Sheehan syndrome, TRH resistance
214
Hurthle cells are associated with what?
Hashimoto's thyroiditis
215
Which cell type is involved in Hashimoto's thyroiditis?
CD8+ Cytotoxic T-cells
216
Is there a goitre in primary atrophic hypothyroidism?
No goitre
217
What drug is used for the management for Myxoedema coma?
Liothyronine (T3)
218
Which gender is affected the most in Graves' disease?
Females 9:1
219
Which antibody is associated with Graves' disease?
Anti-TSH-receptor antibody
220
What is Plummer's disease?
Toxic multinodular goitre
221
Which hyperthyroidism is associated with low uptake?
Subacute De Quervain's thyroiditis
222
Why does lid-lag occur in hyperthyroidism?
Superior tarsal muscle is sensitised to catecholamines
223
What ocular manifestation is associated with Graves' disease?
Graves orbitopathy - proptosis and exopthalmos
224
What nail condition is associated with Graves' disease?
Thyroid acropachy
225
How does potassium iodide establish a euthyroid state prior to surgery?
Via the Wolf-Chaikoff effect
226
What diameter defines a pituitary tumour as a macroadenoma?
>10 mm (1 cm)
227
What are the common symptoms associated with a macroadenoma?
Bitemporal hemianopia and headache
228
What is the prolactin threshold that is diagnostic for a prolactinoma as opposed to a non-functioning pituitary tumour?
Prolactin >6000
229
What is the first line investigation for a prolactinoma?
Serum prolactin
230
What is the first-line treatment for a prolactinoma?
Cabergoline
231
What is the second-line investigation for a suspected prolactinoma?
Pituitary MRI + Perimetry
232
What is the definitive management for a prolactinoma?
Trans-sphenoidal surgery
233
What is the gold-standard investigation for acromegaly?
oral glucose tolerance test - paradoxical increase in growth hormone
234
What is the frequent surveillance indicated for acromegaly?
Colonoscopy
235
Which serum marker is raised in acromegaly?
Serum IGF-1
236
What is the first line of management for acromegaly?
Trans-sphenoidal surgery
237
Why is cabergoline added post-operatively following a TSS-Surgery for acromegaly?
Lactotroph origin expressing D2 receptors
238
What are the three hormones that are administered for a combined pituitary function test?
GnRH (100 mcg) - increases LH/FSH
TRH (200 mcg) - TSH and prolactin
Insulin (0.15 units/kg) CRH and Growth hormone
239
How much should growth hormone increase by in 30 minutes following a combined pituitary function test?
>3
240
How much should cortisol increase by following a combined pituitary function test?
>450
241
TSH, LH FSH increase by how much following a combined pituitary function test (at 30 minutes)?
>10
242
Following a combined pituitary function test, when should pituitary hormones be assessed?
30 minutes (for 2 hours)
243
A combined pituitary function test is contraindicated in what conditions?
IHD, epilepsy, untreated hypothyridism
244
What are the side effects associated with a combined pituitary function test?
Sweating, palpitations, loss of consciousness, transient metal taste in the mouth and flushing
245
An insulin tolerance test should cause glucose to follow what level?
<2.2 mmol/L
246
Which 2 hormones are stimulated following an insulin tolerance stress test?
Cortisol and growth hormone
247
Which 2 hormones are stimulated following a TRH stress test?
TSH and prolactin
248
What are the manifestations of multiple endocrine neoplasia type 1? 3 ps
Parathyroid hyperplasia
Pituitary tumours e.g., Prolactinoma, growth hormone
Pancreatic tumours e.g., Zollinger-Ellison syndrome.
249
What are the manifestations of MEN type 2a?
Parathyroid hyperplasia
Phaeochromocytoma
Thyroid medullary carcinoma
250
What are the manifestations of MEN type 2b?
Phaeochromocytoma
Thyroid medullary carcinoma
Mucosal neuromas
Associated with a Marfanoid habitus
251
Which MEN syndrome is associated with a Marfanoid habitus?
MEN 2b
252
What is the most common cause of primary adrenal insufficiency in the developed world?
Autoimmune aetiology e.g., Autoimmune polyendocrine syndrome type 1
253
Which infectious are associated with primary adrenal insufficiency?
Tuberculosis
254
Why is there hyperpigmentation associated with primary adrenal insufficiency (Addison's)?
Due to increased levels of POMC precursor and MSH levels
255
What are electrolyte abnormality is associated with Addison's disease?
Reduced potassium excretion = Hyperkalaemia
Reduced sodium reabsorption = Hyponatraemia
256
What is the acid-base balance for Addison's disease?
Metabolic acidosis
257
What is the most common enzyme deficiency associated with CAH?
21-hydroxylase (associated with increased testosterone)
258
11b hydroxylase deficiency is associated with what?
Accumulation of 11-deoxy cortisone - increased mineralocorticoid activity and cortisol deficiency
259
17-hydroxylase deficiency is associated with what?
Reduced cortisol, oestrogens and androgens
260
Which complication of fulminant meningococcemia is associated with adrenal insufficiency?
Waterhouse Friedricschen Syndrome
261
What syndrome is associated with co-existing hypoadrenalism and hypothyroidism?
Schmidt's syndrome
262
What is the cause of central adrenal insufficiency?
Pituitary gland dysfunction
263
What is the main cause of tertiary adrenal insufficiency?
Hypothalamic dysfunction
264
What is the first line of investigation for suspected adrenal insufficiency?
Morning 9 am cortisol and serum ACTH
265
What test is diagnostic for adrenal insufficiency?
Short SynACTHen test
Low = primary
Rise = Tertiary or central
266
What is the most important hormone to replace in primary adrenal insufficiency?
Hydrocortisone (most important) and Fludrocortisone
267
What is the most common cause of Cushing's disease?
Pituitary tumour
268
Where is cortisol produced in the adrenal gland?
Zona fasciculata
269
What are the two ACTH-dependent causes of Cushing's?
Pituitary tumour and ectopic-ACTH
270
What are the two ACTH-independent causes for Cushing's syndrome?
Adrenal adenoma and iatrogenic
271
What are the symptoms of Cushing's?
Moon face
Buffalo hump
Central obesity, striae, acne
Hypertension
Diabetes
Proximal myopathy
Hirsutism
Bruising
272
What are the first line investigations for suspected Cushing's syndrome?
24-hour urine free cortisol or late evening salivary cortisol OR overnight dexamethasone suppression test
273
What is the second line investigation for suspected Cushing's?
Serum ACTH to differentiate the two causes
274
For ACTH-independent causes of Cushing's, what is the next-line of investigation?
CT adrenals followed by adrenalectomy
275
What is the diagnostic investigation to confirm ACTH dependent causes of Cushing's syndrome?
Bilateral inferior petrosal sinus sampling
276
What is the first line management for ACTH-independent adrenal causing Cushing's?
Adrenalectomy and steroid replacement
277
Which hormones are produced by the zona glomerulosa?
Mineralocorticoids e.g., aldosterone
278
Which zone of the adrenal cortex produces cortisol?
Zona fasciulata
279
Which zone of the adrenal cortex produces sex hormones?
Zona reticularis
280
Where are catecholamines made?
Adrenal medulla
281
Which cells form part of the RAAS?
Macula densa
282
What is the role of renin?
Stimulates the conversion of angiotensinogen to angiotensin-I
283
What is the of ACE?
Converts angiotensin-I to angiotensin-II
284
Function of angiotensin-2?
Stimulates aldosterone synthesis from the Zona granulosa of the adrenal cortex
285
What is the most common cause of primary hyperaldosteronism?
Bilateral adrenal hyperplasia
286
What is Conn's syndrome?
Adrenal adenoma
287
What is the complication following an adrenalectomy?
Nelson's syndrome (pituitary enlargement due to depleted negative feedback resulting in compressing of the stalk
288
What electrolyte imbalance is associated with primary hyperaldosteronism?
Hypokalaemia, Hypernatraemia, metabolic alkalosis
289
What acid base disturbance is associated with hypokalaemia?
Metabolic alkalosis
290
What is the first line of investigation for Primary hyperaldosteronism?
Aldosterone: renin ratio (Raised – renin suppressed) = >40.
291
Which drug is used to manage primary hyperaldosteronism?
spironolactone, eplerenone
292
Which cells are implicated in a phaeo?
chromaffin cells
293
Which familial syndromes predispose the development of a phaeo?
Von-Hippel Lindau
MEN2
NF1
294
Which nests are seen in a phaeo?
Zellballen nests of chromaffin cells
295
What % of Phaeos are bilateral, and associated with syndromes?
10%
296
What is a paraglioma?
Secretes noradrenaline - sympathetic chain
297
What urinary test is used for the diagnosis of a phaeo?
24h urinary metadrenaline/metanephrine
298
What precursor molecule is used to screen for a phaeo?
Meta-lodobenzylguanidine scan (MIBG)
299
Which drug is given first in a phaeo?
Alpha blockade (first) – phenoxybenzamine
300
What drug class is given second for a phaeo?
Beta blockade – Propranolol, atenolol, metoprolol
301
What is the normal range for calcium?
2.2 to 2.6
302
What is the formula for corrected calcium?
Serum Ca + 0.02 x (40 –
serum albumin (g/l))
303
How is most calcium transported across the body?
50% bound to albumin
304
Which enzyme is upregulated by PTH?
tubular 1-alpha-hydroxylation
305
What effect does PTH have on phosphate?
Increased renal phosphate EXCRETION
306
What effect does calcitriol have?
Calcium and phosphate reabsorption from the gut.
Bone remodelling
307
Which type of vitamin D is from plants?
Ergocalciferol
308
Where is 25-hydroxylase found?
Liver
309
Which enzyme is responsible for the activation of 25-hydroxy-vitamin D?
1-alpha-hydroxylase
310
Where does 1-alpha-hydroxylase work?
Proximal renal convoluted tubule
311
Which receptors are responsible for detecting serum calcium?
Calcium sensing receptor
312
Which parathyroid gland cells product PTH?
Chief cells
313
Which is the most common cause of primary hyperparathyroidism?
Single parathyroid adenoma
314
What are the common causes of secondary hyperparathyroidism?
Chronic kidney disease
* Vitamin D deficiency
* Malabsorption syndromes
315
What are the causes of tertiary hyperparathyroidism?
parathyroid gland hyperplasia
316
Which lung cancer is responsible for hypercalcaemia of malignancy?
Squamous cell lung carcinoma
317
What is the metabolic panel results for osteoporosis?
Normal
318
What blood marker is raised for Paget's disease?
ALP
319
Which two markers are raised for Osteomalacia?
Raised ALP and PTH
320
What is the calcium level in secondary HyperPTH?
Low
321
Which syndrome is associated with type 1 pseudohypoparathyroidism?
Albright’s Hereditary Osteodystrophy phenotype
322
Which signs is characterised by ipsilatearl twitching of the upper lip and side of the mouth in hypocalcaemia?
Chvostek’s sign
323
Which sign is associated with a carpal spasm?
Trousseau’s sign
324
What is pseudopseudohypoparathyroidism?
phenotypic expression of ABO without PTH resistance.
325
What are the features of Albright Hereditary Osteodystrophy?
Short stature
* Round face
* Shortened fourth/fifth metacarpal bones.
* Lab: Hypocalcaemia and hyperphosphatemia + raised PTH.
326
What is the commonest cause of hypercalcaemia in the community?
Primary hyperparathyroidism
327
What is the commonest cause of hypercalcaemia in hospitals?
Malignancy
328
What ECG changes are associated with hypercalcaemia?
Prolonged PR interval, short QT interval, widened QRS complex and bradycardia
329
What is the first line management for hypercalcaemia?
IV fluids and bisphosphonates
330
What is the inheritance pattern for Familial Hypocalciuric Hypercalcaemia?
Autosomal dominant
331
Which mutation is implicated in Familial Hypocalciuric Hypercalcaemia?
CaSR mutation - Decreased receptor activity - increased set point of calcium sensing (higher than normal calcium to suppress PTH)
332
What is the most common cause of hypocalcaemia?
PTH deficiency secondary to iatrogenic insult
333
Which mutation is involved in Tangier disease?
ABCA-1 gene
334
Which transporter protein transports cholesterol across the intestinal epitheilum?
NPC1L1
335
Which drug is used to reduce sterol absorption?
Ezetimibe
336
Which ATP transport proteins are implicated in intestinal cholesterol absorption?
ABCG5 * ABCG8
337
Where are bile acids reabsorbed?
Terminal ileum
338
What is the order lipoprotein density?
Chylomicron < FFA < VLDL < LDL < IDL < HDL
339
Which enzyme converts acetate and mevalonic acid into cholesterol?
HMG CoA reductase
340
Which enzyme promotes the degradation of LDLR?
PCSK9
341
What is the mechanism of action for Evolocumab?
Anti-PCSK9 Monoclonal antibody
342
Which enzyme hydroxylates cholesterol into bile acids?
7-alpha hydroxylase
343
Which enzyme esterifies cholesterol?
ACAT
344
Which enzyme packages free cholesterol into HDL?
ABC A1
345
Which transfer protein mediates the movement of cholesterol from HDL to VLDL?
Cholesteryl ester transfer protein
346
What is the protein involved in lomitapide?
Microsomal TG Transfer Protein Inhibitor
347
Which enzyme is inhibited in statin therapy?
HMG-CoA reductase
348
What is the mechanism of action for orlistat?
Pancreatic lipase inhibitor
349
What is the BMI threshold for bariatric surgery?
BMI >40Kg/m2
350
Type 3 hyperlipidaemia is associated with which APOE protein?
APOE2
351
Which vitamin is responsible for retinitis pigmentosa?
Vitamin A
352
Which vitamin is deficient in beri beri?
B1 thiamine
353
What causes pellagra?
Niacin
354
What is the effect of b6 deficiency?
Neuropathy
355
Which type of anaemia is associated with b12 deficiency?
Pernicious anaemia
356
What is the effect of iodine deficiency?
Hypothyroidism and goitre
357
Zinc deficiency causes what?
Dermatitis
358
Which vitamins are deficient in coeliac disease?
ADEK
359
Which enzyme is increased in parotitis?
Serum amylase-S
360
What is the marker of chronic pancreatitis?
Faecal elastase
361
Which raised enzyme marker is highly indicates of acute pancreatitis?
Lipase
362
What is the marker of skeletal muscle damage?
CK-MM
363
What is the marker for cardiac muscle damage?
CK-MB
364
What are the risk factors for statin related myopathy?
High dose
o Genetic predisposition
o Previous history of myopathy
o Polypharmacy (fibrates, cyclosporin)
365
What is the effect of statin related myopathy?
Rhabdomyolysis
366
Which marker is raised in stain-related myopathy?
CK-MM
367
Which is a good marker for suspected reinfarction?
CK-MB
368
Which enzyme differentiates from liver and bone raised ALP?
GGT
