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Flashcards in ChemPath (finished) Deck (362):
1

What % of the body is water?

60%

2

What is the ratio of fluid in the body in terms of intracellular:extracellular?

2:1

3

Which compartments make up the body's extracellular fluid?

-Intravascular
-Interstitial
-Transcellular

4

What is the function of interstitial fluid?

Bathes cells + makes up the largest component of ECF

5

What is transcellular fluid/where is it?

Within epithelial lined spaces e.g. CSF, joint fluid, bladder urine, aqueous humour

6

What is osmolality?

The total number of particles in a solution

7

What are the units for osmolality?

mmol/kg

8

What is osmolarity?

2(Na + K) + urea + glucose

9

What are the units of osmolarity?

mmol/L

10

What are the determinants of osmolarity?

Physiological: sodium, potassium, chlorine, HCO3, urea, glucose
Pathological: endogenous (e.g. glucose), exogenous (e.g. ethanol, mannitol)

11

What is the osmolar gap?

The difference between osmolarity and osmolality

12

What is the normal range for osmolality?

275-295 mmol/kg

13

What is the normal range for sodium?

135-145 mmol/L

14

How much sodium is freely exchangeable and where is the rest of it?

70% - rest is complexed in bone

15

Is sodium predominantly intracellular or extracellular?

Extracellular

16

What maintains sodium levels?

Active pumping from ICF to ECF by Na+/K+ ATPase

17

Which fluid volume directly depends on sodium?

ECF

18

How should you manage mild hyponatraemia?

Treat the underlying cause not the sodium level provided it's not severe

19

What are the features of symptomatic hyponatraemia?

-Nausea and vomiting (

20

What measure should you use to determine if someone has true hyponatraemia?

Osmolality

21

What might be the cause of hyponatraemia if serum osmolality is high?

Glucose/mannitol infusion

22

What might be the cause of hyponatraemia if serum osmolality is normal?

Spurious - drip arm sample
Pseudohyponatraemia: hyperlipidaemia, paraproteinaemia

23

What might be the cause of hyponatraemia if serum osmolality is low?

True hyponatraemia

24

What is TURP syndrome?

Hyponatraemia from water absorbed through a damaged prostate

25

If you have a hyponatraemic patient with a low osmolality, what measure should you look at next to determine the cause?

Hydration status and urinary Na

26

What are the causes of hyponatraemia where a patient is hypovolaemic with urinary sodium >20?

Renal - diuretics, Addison's, salt losing nephropathies

27

What are the causes of hyponatraemia where a patient is hypovolaemic with urinary sodium

Non renal - vomiting, diarrhoea, excess sweating, third space losses (ascites, burns) - depending on fluid replacement

28

What are the causes of hyponatraemia where a patient is euvolaemic with urinary sodium >20?

SIADH, primary polydipsia, severe hypothyroidism

29

What are the causes of hyponatraemia where a patient is hypervolaemic with urinary sodium >20?

ARF, CRF

30

What are the causes of hyponatraemia where a patient is hypervolaemic with urinary sodium

Cardiac failure, cirrhosis, inappropriate IV fluid

31

What isWhat tests should you do in a patient who is hyponatraemic and euvolaemic?

TFT, short synacthen test, paired urine serum osmolality

32

What is the risk with rapidly correcting hyponatraemia?

Central pontine myelinolysis

33

What are the features of central pontine myelinolysis?

Pseudo bulbar palsy, paraparesis, locked-in syndrome

34

At what rate should you aim to correct hyponatraemia?

Increase Na+ by 1 mmol/l per hour

35

What are some causes of hyponatraemia pos surgery?

-Overhydration with hypotonic IV fluids
-Transient increase in ADH due to stress of surgery

36

What are the laboratory criteria for a diagnosis of SIADH?

-True hyponatraemia
-Clinically euvolaemic
-Inappropriately high urine osmolality and increased renal sodium excretion (>20 mmol/l)
-Normal renal, adrenal, thyroid and cardiac function

37

What are the causes of SIADH?

-Malignancy: small cell lung ca (most common), pancreas, prostate, lymphoma (ectopic secretion)
-CNS disorders: meningoencephalitis, haemorrhage, abscess
-Chest disease: TB, pneumonia, abscess
-Drugs: opiates, SSRIs, carbamazepine

38

How is hypernatraemia defined?

Usually clinically significant - plasma Na+ >148 mmol/l

39

What are some common scenarios in which patients become hypernatraemic?

Iatrogenic, ITU patients

40

What are the symptoms of hypernatraemia?

Thirst
Confusion
Seizures and ataxia
Coma

41

What is the risk of rapid correction of hypernatraemia?

Cerebral oedema

42

What are the causes of hypernatraemia in a hypovolaemic patient?

GI loss: vomiting, diarrhoea
Skin loss: excessive sweating, burns
Renal loss:
-Loop diuretics
-Osmotic diuretics (glucose, mannitol)
-Renal disease (impaired concentrating ability)

43

What are the causes of hypernatraemia in a euvolaemic patient?

Respiratory loss: tachypnoea
Skin loss: excessive sweating, fever
Renal loss: diabetes insipidus
Misc: no water

44

What are the causes of hypernatraemia in a hypervolaemic patient?

Mineralocorticoid excess (Conn's syndrome)
Hypertonic saline

45

What are the clinical features of diabetes insipidus?

-Hypernatraemia (lethargy, thirst, irritability, confusion, coma, fits)
-Clinically euvolaemic
-Polyuria and polydipsia
-Urine: plasma osmolality

46

What are the 2 main types of diabetes insipidus?

Cranial and nephrogenic

47

What is cranial diabetes insipidus?

Where there is a lack of/no ADH

48

What are the causes of cranial diabetes insipidus?

Head trauma
Tumour
Surgery

49

What is nephrogenic diabetes insipidus?

Where there is a receptor defect leading to insensitivity to ADH

50

What are the causes of nephrogenic diabetes insipidus?

Inherited
Lithium
Chronic renal failure

51

How do you diagnose diabetes insipidus?

8 hour fluid deprivation test

52

What happens in a normal 8 hour fluid deprivation test?

Urine concentration rises to >600 mOsmol/kg

53

What happens in an 8 hour fluid deprivation test with primary polydipsia?

Urine concentrates >400-600 mOsmol/kg

54

What happens in an 8 hour fluid deprivation test with cranial diabetes insipidus?

Urine concentrates only after giving desmopressin

55

What happens in an 8 hour fluid deprivation test with nephrogenic diabetes insipidus?

Zero concentration of urine including after desmopressin

56

What is the normal range for potassium?

3.5-5.5 mmol/l

57

Is potassium mainly intracellular or extracellular?

Intracellular - only 2% is extracellular

58

What maintains potassium in the intracellular fluid?

Active pumping from ECF -> ICF by Na+/K+ ATPase

59

How much of potassium is freely exchangeable and where is the rest of it?

90% - rest is bound in RBCs, bone, brain tissue

60

What ion is potassium linked to (other than sodium)

H+ - as one moves into cells the other moves out

61

For every drop in pH of 0.1, what is the change in K+?

Increases by 0.7

62

How is hypokalaemia defined?

Potassium

63

What are the two main mechanisms of hypokalaemia?

Depletion or shift into cells - rarely ue to decreased intake

64

What are some common causes of hypokalaemia?

-GI loss
-Renal loss: hyperaldosteronism, excess cortisol, increased sodium delivery to distal nephron, osmotic diuresis
-Redistribution into cells: insulin, beta agonists, alkalosis

65

What are some rare causes of hypokalaemia?

Tubular acidosis type 1 + 2, hypomagnesaemia

66

How is hyperkalaemia defined?

Potassium >5.5 mmol/l

67

How common is hyperkalaemia compared to hypokalaemia?

Less common but more dangerous

68

What are the 3 main mechanisms behind hyperkalaemia?

Excessive intake
Transcellular movement (ICF>ECF)
Decreased excretion

69

What are some causes of excessive potassium intake?

Oral (fasting)
Parenteral
Stored blood transfusion

70

What are some causes of transcellular movement of potassium?

Acidosis
Insulin shortage
Tissue damage/catabolic state

71

What are some causes of decreased excretion of potassium?

Acute renal failure (oliguric phase)
CRF (late)
K sparing diuretics (spironolactone)
Mineralocorticoid deficiency (Addisons)
NSAIDs
ACEI

72

What is a normal pH?

7.35-7.45

73

What is a normal CO2?

4.7-6.0 kPa

74

What is a normal bicarbonate?

22-30 mmol/L

75

What is a normal O2?

10-13 kPa

76

What is the equation for [H+] using CO2 and HCO3?

[H+] = 180 x ([CO2]/[HCO3])

77

What is the pH, bicarb and CO2 in metabolic acidosis?

Low pH
Low bicarb
Normal CO2 or low if compensated

78

What is the pH, bicarb and CO2 in metabolic alkalosis?

High pH
High bicarb
Normal CO2 or high if compensated

79

What is the pH, bicarb and CO2 in respiratory acidosis?

Low pH
Normal bicarb or high if compensated
High CO2

80

What is the pH, bicarb and CO2 in respiratory alkalosis?

High pH
Normal bicarb or low if compensated
Low CO2

81

What are the causes of metabolic acidosis?

Lactate build up
DKA
Renal tubular acidosis

82

What are the causes of metabolic alkalosis?

Pyloric stenosis
Hypokalaemia

83

What are the causes of respiratory acidosis?

Lung injury - pneumonia, COPD
Decreased ventilation

84

What are the causes of respiratory alkalosis?

Mechanical ventilation
Anxiety/panic attack

85

What is 'compensation' (acid base)?

Return of pH towards normal at the expense of other values

86

What are the anion and osmolar gaps useful for?

Screening for organic poisoning, DKA, and to provide more information about a metabolic acidosis

87

How do you calculate the anion gap?

(Na+ + K+) - (Cl- + HCO3)

88

What is the anion gap?

Difference between the total concentration of principal cations and principal anions = concentration of unmeasured anions in plasma

89

What almost entirely makes up the anion gap?

Albumin

90

What is the normal range for the anion gap?

14-18 mmol/L

91

What are the causes of elevated anion gap metabolic acidosis?

KULT
Ketoacidosis (DKA, alcoholic, starvation)
Uraemia (renal failure)
Lactic acidosis
Toxins (ethylene glycol,methanol, paraldehyde, salicylate)

92

What defines mild hyponatraemia?

Sodium

93

What defines severe hyponatraemia?

Sodium

94

What is a normal osmolar gap?

95

how do you calculate the osmolar gap?

Osmolality (measured) - osmolarity (calculated)

96

What does an elevated osmolar gap mean?

That there is extra solute in the plasma e.g. ethylene glycol, ethanol, methanol, mannitol

97

Why is osmolar gap helpful?

To differentiate between causes of elected anion gap metabolic acidosis

98

What are the LFT markers of liver cell damage?

ALT
AST
Alk phos
GGT
Bilirubin

99

What are the LFT markers of liver synthetic function?

Clotting (INR)
Albumin
Glucose

100

What are the aminotransferases?

AST And ALT

101

What is a normal aminotransferase?

102

When are the aminotransferases raised?

When hepatocytes die

103

What is the pattern of aminotransferases in alcoholic liver disease?

AST:ALT = 2:1

104

What is the pattern of aminotransferases in viral liver disease?

AST:ALT =

105

What is a normal alkaline phosphatase?

30-150 iu/L

106

When is ALP raised?

Cholestasis (intra or extra hepatic), bone disease, and ++ in pregnancy

107

What is a normal gamma GT?

30-150 iu/L

108

When is gamma GT elevated?

Chronic alcohol use, bile duct disease and metastases

109

What is gamma GT useful for?

To confirm hepatic source of ALP

110

What are the porphyrias?

A group of 7 disorders caused by deficiency in enzymes involved in haem biosynthesis, leading to a build up of toxic haem precursors

111

What is acute intermittent porphyria?

An autosomal dominant disorder in which there is an HMB (hydroxymethylbilane) synthase deficiency

112

What are the symptoms of acute intermittent porphyria?

NEUROVISCERAL ONLY:
Abdo pain
Seizures
Psych disturbances
Nausea and vomiting
Tachycardia
Hypertension
Sensory loss
Muscle weakness
Constipation
Urinary incontinence

113

Why are there no cutaneous manifestations in acute intermittent porphyria?

Absence of porphyrinogens

114

How do you diagnose acute intermittent porphyria?

ALA and PBG in urine - 'port wine urine'

115

What are the precipitating factors in acute intermittent porphyria?

ALA syntheses inducers (steroids, ethanol, barbiturates)
Stress (infections, surgery)
Reduced caloric intake and endocrine factors (e.g. premenstrual)

116

How do you treat acute intermittent porphyria?

Avoid precipitating factors
Analgesia
IV carbohydrate/haem arginate

117

What is acute porphyria with skin lesions?

Hereditary coproporphyria (HCP) + variegate porphyria (VP); autosomal dominant condition

118

What are the features of hereditary coproporphyria?

Neurovisceral and skin lesions
Raised porphyrins in faeces or urine

119

Which non-acute porphyrias have skin lesions only?

Congenital erythropoietic porphyria
Erythropoietic protoporphyria
Porphyria cutanea tarda

120

What are the features of erythropoietic protoporphyria?

Photosensitivity
Burning, itching, oedema following sun exposure

121

What is porphyria cutanea tarda?

Inherited or acquired deficiency in uroporphyrinogen decarboxylase

122

What are the symptoms of porphyria cutanea tarda?

Vesicles (causing, pigmented, superficial scarring) on sun exposed sites

123

How do you diagnose porphyria cutanea tarda?

Increased urinary uroporphyrins and coproporphyrins
Increased ferritin

124

What's the treatment for porphyria cutanea tarda?

Avoid precipitants (alcohol,hepatic compromise), phlebotomy

125

Which pituitary hormones does GHRH stimulate?

GH

126

Which pituitary hormones GnRH stimulate?

FSH and LH

127

Which pituitary hormones TRH stimulate?

TSH, prolactin

128

Which pituitary hormones dopamine stimulate?

Inhibits prolactin

129

Which pituitary hormones CRH stimulate?

ACTH

130

What are the indications for a combined pituitary function test?

Assessment of all components of anterior pituitary function - particularly in pituitary tumours or following tumour treatment

131

What are the contraindications to doing a combined pituitary function test?

Ischaemic heart disease
Epilepsy
Untreated hypothyroidism (impairs the GH and cortisol responses)

132

What are the side effects of doing a combined pituitary function test?

Sweating, palpitations, loss of consciousness
Rarely: convulsions with hypoglycaemia
With the TRH injection may get transient symptoms of metallic taste in the mouth, flushing and nausea

133

What are the 3 components of the combined pituitary function test?

Insulin tolerance test
Thyrotrophin releasing hormone test
Gonadotrophin releasing hormone test

134

How do you interpret the insulin tolerance test?

Adequate cortisol response: increase from >170 nmol/L to >500 nmol/L
Adequate GH response: increase to > 6mcg/L

135

What is a normal result in the thyrotrophin releasing hormone test?

TSH rise to >5 u/L (30 min value > 60 min value)

136

What is a result in the thyrotrophin releasing hormone test indicating primary hypothalamic disease?

IF the 60 min value > 30 min value

137

What is a result in the thyrotrophin releasing hormone test indicating hyperthyroidism?

TSH remains supressed

138

What is a result in the thyrotrophin releasing hormone test indicating hypothyroidism?

Exaggerated response

139

Why isn't dynamic testing usually needed to diagnose hyperthyroidism?

Because current TSH assays are sensitive enough for basal levels to be adequate

140

What is a normal gonadotrophin releasing hormone test result?

Normal peaks can occur at 30 or 60 minutes/ LH should be >10U/L and FSH >2U/L

141

What is an inadequate gonadotrophin releasing hormone test result indicative of/

Can be a possible early indicator of hypopituitary

142

How is gonadotrophin deficiency diagnosed?

On basal levels:
-Male - low testosterone in absence of increased basal gonadotrophin
Female - low estradiol without raised basal gonadotrophin and no response to clomiphene

143

How should pre pubertal children respond to the gonadotrophin releasing hormone test?

Should have no response of LH or FSH to LHRH

144

How will the pituitary respond in a gonadotrophin releasing hormone test in e.g. precocious puberty

Sex steroids present -> pituitary is 'primed' -> will respond to LHRH

145

What do you have to be careful of before the test with the gonadotrophin releasing hormone test?

Shouldn't prime the pituitary with steroids

146

What hormones will a pituitary tumour produce?

Any combination of pituitary hormones

147

How is a pituitary micro adenoma defined?

148

How is a pituitary macro adenoma defined?

>10mm - usually aggressive

149

What visual defect can a pituitary adenoma cause?

Bitemporal hemianopia due to compression of the optic chiasm

150

What are the hormones of the anterior pituitary?

ADH and oxytocin

151

What might cause excess ADH?

-LUNG: paraneoplasias: SCC, small cell, pneumonia
-BRAIN: traumatic brain injury, meningitis
-IATROGENIC: SSRIs, amitryptilline

152

What is the effect of excess ADH?

SIADH -> euvolaemic hyponatraemia

153

What are the causes of ADH failure?

-Diabetes insipidus
-Neurogenic (failure of production, 50% idiopathic)
-Nephrogenic (commonly iatrogenic from lithium, also hypercalcaemia, renal failure)
-Dipsogenic (failure/damage to the hypothalamus and thirst drive, hypernatraemia without increased thirst response)

154

What is diabetes insipidus?

Increased diuresis due to either failure of production or insensitivity to ADH, leads to decreased urine osmolality and increased serum osmolality

155

What does oxytocin do?

Increases uterine contraction and expulsion of milk

156

What can you given in failure of oxytocin production e.g. to help breastfeeding?

Syntocinon

157

What can you use as an oxytocin antagonist in tocolysis?

Atosiban

158

What are the causes of normal TSH with an abnormal T4?

-Assay interference
-Changes in TBG
-Amiodarone

159

What are the causes of low TSH?

-High T4 or high T3: hyperthyroidism
-Normal T3 and T4: subclinical hyperthyroidism
-Low T4: central hypothyroidism (hypothalamic/pituitary disorder)

160

What are the causes of a high TSH?

-Low T4: hypothyroidism
-Normal T4: treated or subclinical hypothyroidism (look for associated increased cholesterol)
-High T4: TSH secreting tumour or thyroid hormone resistance
-Later low TSH and low T3 and T4: sick euthyroidism (with any severe illness)

161

What are causes of hyperthyroidism with high uptake?

Graves disease (40-60%, F>M 9:1, autoantibodies ++, high uptake on isotope scan)
Toxic multi nodular goitre (30-50%, high uptake)
Toxic adenoma (5%, 'hot nodule' on isotope scan)

162

What are causes of hyperthyroidism with low uptake?

Subacute deQuervain's thyroiditis - self limiting post viral painful goitre
Postpartum thyroiditis

163

What is the treatment for hyperthyroidism with high uptake?

Beta blocker and antithyroid therapy (carbimazole/propylthiouracil)
Can also use radio iodine or surgery

164

Why is propylthiouracil not really used now?

Risk of aplastic anaemia

165

What can you use propylthiouracil for in high uptake hyperthyroidism?

To block and replace or titrate to TSH

166

What is the treatment for hyperthyroidism with low uptake?

Symptomatic - beta blockers and NSAIDs for de Quervain's

167

What are the autoimmune causes of hypothyroidism?

Primary atrophic hypothyroidism
Hashimoto's thyroiditis

168

What are the features of primary atrophic hypothyroidism?

Diffuse lymphocytic infiltration and atrophy, no goitre

169

What are the features of Hashimoto's thyroiditis?

Plasma cell infiltration and goitre. Elderly females. May be initial Hashitoxicosis. ++ autoantibody titres

170

What are the non autoimmune causes of hypothyroidism?

-Iodine deficiency (common worldwide)
-Post thyroidectomy/radioiodine
-Drug induced: antithyroid drugs, lithium, amiodarone

171

What is the treatment for hypothyroidism?

Thyroid replacement therapy

172

What are the 5 kinds of thyroid neoplasia?

Papillary
Follicular
Medullary
Lymphoma
Anaplastic

173

What are the features of papillary thyroid cancer?

>60% cases
30-40 years old
Surgery +/- radioiodine
Thyroxine to lower TSH

174

What are the features of follicular thyroid cancer?

25%
Middle aged
Well differentiated but spreads early
Surgery + radioiodine + thyroxine

175

What are the features of medullary thyroid cancer?

5% originates in parafollicular cells
Linked to MEN2
Produce calcitonin

176

What are the features of lymphoma thyroid cancer?

5% MALT origin
Risk factor: chronic Hashimotos
Good prognosis

177

What are the features of anaplastic thyroid cancer?

Rare
Elderly
Poor response to any treatment

178

What are the causes of Cushing's?

Pituitary tumour (85%, Cushing's disease)
Adrenal tumour 10%
Ectopic ACTH producing tumour 5%
Iatrogenic: steroid use

179

What are the causes of Addisons?

Autoimmune
TB
Tumour deposits
Adrenal haemorrhage
Amyloid deposits

180

What are the causes of Conn's?

Adrenal tumour

181

What are the causes of Phaeo?

Adrenal medulla tumour = increased adrenaline

182

What are the symptoms and signs of Cushing's?

Moon face
Buffalo hump
Striae, acne
Hypertension
Diabetes
Muscle weakness (proximal myopathy)
Hirsutism

183

What are the symptoms and signs of Addison's?

High potassium
Low sodium and glucose
Postural hypotension
Skin pigmentation
Lethargy
Depression

184

What are the symptoms and signs of Conn's?

Uncontrollable hypertension
High sodium
Low potassium

185

What are the symptoms and signs of phaeo?

Hypertension
Arrhythmias
Death if untreated

186

What investigations should you do in Cushing's?

Low dose dexamethasone
High dose dexamethasone
Cortisol levels

187

What investigations should you do in Addison's?

SynACTHen test

188

What investigations should you do in Conn's?

Aldosterone:renin ratio

189

What investigations should you do in phaeo?

Plasma + 24h urine met adrenaline measurement/catecholamines + VMA

190

How should you treat Cushing's?

Treat the underlying cause e.g. surgical removal of lesion

191

How should you treat Addison's?

Hormone replacement: hydrocortisone/fludrocortisone if primary adrenal lesion

192

How should you treat Conn's?

Aldosterone antagonists/K sparing diuretics: spironolactone, eplerenone, amiloride

193

How should you treat phaeo?

Alpha blockade
Beta blockade
Then surgery when blood pressure well controlled

194

What are the signs of phenytoin toxicity?

Ataxia and nystagmus

195

What are the signs of digoxin toxicity?

Arrhythmias
Heart block
Confusion
Xanthopsia (seeing yellow)

196

What are the signs of lithium toxicity?

Tremor (early)
Lethargy
Fits
Arrhythmia
Renal failure

197

What are the signs of gentamicin toxicity?

Tinnitus
Deafness
Nystagmus
Renal failure

198

What are the signs of theophylline toxicity?

Arrhythmias
Anxiety
Tremor
Convulsions

199

What is phenytoin mainly used for?

Seizures

200

What is digoxin mainly used for?

Arrhythmias

201

What is lithium mainly used for?

Relapse of mania in bipolar disorder

202

What is gentamicin mainly used for?

Uncontrolled infection

203

What is theophylline mainly used for?

COPD, asthma - relaxes bronchial smooth muscle

204

What are the interactions and cautions of phenytoin?

At high levels the liver becomes saturated leading to a surge in blood levels

205

What are the interactions and cautions of digoxin?

Levels increased with hypokalaemia
Reduce dose in renal failure and elderly

206

What are the interactions and cautions of lithium?

Excretion impaired by hyponatraemia, decreased renal function and diuretics

207

What are the interactions and cautions of gentamicin?

Mostly use single daily dosing. Monitor peak and trough level before next dose

208

What are the interactions and cautions of theophylline?

Variation in half life e.g. 4 hours in smokers and 8 hours in non-smokers, 30 hours in liver disease. Level increased by erythromycin, cimetidine and phenytoin

209

How do you treat phenytoin toxicity?

Omit/reduce dose

210

How do you treat digoxin toxicity?

Digibind (digoxin immune Fab)

211

How do you treat lithium toxicity?

RF may need haemodialysis

212

How do you treat gentamicin toxicity?

Omit/reduce dose

213

How do you treat theophylline toxicity?

Omit/reduce dose

214

What is the normal range for calcium?

2.2-2.6 mmol/L

215

Where is calcium in the body?

45% ionised = free = biologically active
50% bound to albumin, therefore affected by albumin level (use corrected calcium)

216

What are the two main hormones in calcium metabolism?

PTH
1,25 (OH)2 D - calcitriol

217

What are the actions of PTH?

Increases tubular 1alpha hydroxylation of bit D
Mobilises calcium from bone
Increases renal calcium reabsorption
Increases renal phosphate excretion

218

What are the actions of calcitriol?

Increases calcium and phosphate absorption from the gut
Bone remodelling

219

What is this condition?
-High calcium
-Low PO4
-Increased or normal PTH
-Increased or normal ALP
-Normal vitamin D

Primary hyperparathyroidism

220

What is this condition?
-Low or normal calcium
-High PO4
-High PTH
-High ALP
-Normal vitamin D

Secondary hyperparathyroidism

221

What is this condition?
-High calcium
-Low PO4
-Increased PTH
-Increased or normal ALP
-Normal vitamin D

Tertiary hyperparathyroidism

222

What is this condition?
-Low calcium
-High PO4
-Low PTH
-Low or normal ALP
-Normal vitamin D

Hypoparathyroidism

223

What is this condition?
-Low calcium
-Low PO4
-Increased PTH
-Increased ALP
-Low D

Rickets/osteomalacia

224

What is this condition?
-Normal calcium
-Normal PO4
-Normal PTH
-High ALP
-Normal vitamin D

Paget's disease

225

What is this condition if there is bone loss?
-Normal calcium
-Normal PO4
-Normal PTH
-Normal ALP
-Normal vitamin D

Osteoporosis

226

What is the primary defect in primary hyperparathyroidism?

Increased PTH (80% parathyroid adenoma)

227

What is the primary defect in secondary hyperparathyroidism?

Renal osteodystrophy

228

What is the primary defect in tertiary hyperparathyroidism?

Autonomous PTH secretion post renal transplant

229

What is the primary defect in hypoparathyroidism?

Low levels of PTH
Primary: DiGeorge syndrome
Secondary: post thyroid surgery

230

What is the primary defect in rickets/osteomalacia?

Vitamin D deficiency

231

What is the primary defect in PAget's disease?

Remodelling of bone

232

What is the primary defect in osteoporosis?

Bone loss

233

What should be the first step in determining the cause of hypercalcaemia?

Albumin

234

If a patient is hypercalcaemic with high albumin, what might the cause be?

If urea is high - dehydration
If urea is normal - cuffed

235

If a patient is hypercalcaemic with low or normal albumin, what should be the next investigation?

Phosphate

236

If a patient is hypercalcaemic with low/normal albumin and low phosphate what might the cause be?

Primary or tertiary hyperparathyroidism (confirm with raised PTH)

237

If a patient is hypercalcaemic with low/normal albumin and high phosphate what might the next investigation be?

ALP

238

If a patient is hypercalcaemic with low/normal albumin, high phosphate and high ALP what might the cause be?

Increased bone turnover
Bone metastasis
Thyrotoxicosis
Sarcoidosis (increased 1alphaOH)

239

If a patient is hypercalcaemic with low/normal albumin, high phosphate and normal ALP what might the cause be?

Myeloma
Excess vitamin D
Sarcoid
Milk alkali syndrome (and increased bicarbonate)

240

What are the symptoms of hypercalcaemia?

Stones (renal)
Bones (pain)
Groans (psych)
Moans (abdo pain)
Polyuria
Muscle weakness

241

How should you treat hypercalcaemia?

Correct dehydration
Bisphosphonates
Correct cause e.g. chemo for cancer

242

What should be the first investigation in a patient who is hypocalcaemic?

Phosphate

243

What are the causes of hypocalcaemia with raised phosphate?

Chronic kidney disease
Hypoparathyroidism (including post thyroid surgery)
Pseudohypoparathyroidism
Hypomagnesaemia

244

What are the causes of hypocalcaemia with normal/low phosphate?

Osteomalacia
Acute pancreatitis
Over hydration
Respiratory alkalosis (low ionised/active Ca2+)

245

What is a cause of finding hypocalcaemia as an artefact?

Hypoalbuminaemia

246

What are the symptoms of hypocalcaemia?

Perioral paraesthesia
Carpopedal spasm
Neuromuscular excitability (Trousseau's and Ckvostek's sign)

247

What's the treatment for hypocalcaemia?

Mild: give calcium
Chronic kidney disease: alfacalcidol
Severe: 10% calcium gluconate IV

248

What are the risk factors for renal stones?

Dehydration
Abnormal urine pH (meat intake, renal tubular acidosis)
Increased excretion of stone constituents
Urine infection
Anatomical abnormalities

249

What are the causes of calcium stones?

Most patients are normocalcaemic
Results from:
-Hyperoxaluria: increased intake/absorption etc
-Hypercalciuria: increased intake/renal leak

250

How are calcium stones managed preventatively?

Avoid dehydration
Reduce oxalate intake
Maintain Ca intake
Thiazides -> hypocalciuric
Citrate (alkalinise urine)

251

How common are mixed calcium stones and how do they appear on X-ray?

~45% - radioopaque

252

How common are calcium oxalate stones and how do they appear on X-ray?

~35% - radioopaque

253

How common are calcium phosphate stones and how do they appear on X-ray?

~1% - radioopaque

254

How common are triple phosphate 'struvite' stones and how do they appear on X-ray?

~10% - radiopaque 'staghorn'

255

How common are uric acid stones and how do they appear on X-ray?

~5% - radiolucent

256

How common are cysteine stones and how do they appear on X-ray?

~1-2% - radiolucent

257

How common are xanthine stones?

Rare

258

What investigations should be done in recurrent stones?

Serum : Cr, bicarb, Ca, phosphate, urate, PTH (if hypercalcaemic)
Stone analysis
Spot urine: pH, MCS, amino acids, albumin
24h urine: volume (>2.5L), Ca, oxalate, urate, citrate

259

When are amylase levels high?

Acute pancreatitis - >10x upper normal limit

260

What is the most common usage of creatine kinase?

Marker of muscle damage

261

What are the forms of creatine kinase?

CK-MM - skeletal muscle
CK-MB 1 + 2 - cardiac muscle

262

When are creatine kinase levels raised?

Physiological - Afro-Caribbeans (10x normal), MI (>10x normal), statin related myopathy, rhabdomyolysis

263

Where does alkaline phosphatase come from?

High concentrations in liver, bone, intestine and placenta

264

When is alkaline phosphatase raised?

Physiological: pregnancy (3rd trimester), childhood growth spurt
Pathological:
->5x ULN: bone (Paget's, osteomalacia), liver (cholestasis, cirrhosis)
-

265

Which troponin are clinically useful?

I and T - myocardial injury biomarkers

266

When should you measure troponin?

At 6 hours and then 12 hours post onset of chest pain (100% sensitivity and 98% specificity at 12-24 hours)
Remains elevated for 3-10 days

267

What are the diagnostic criteria for an MI?

Either of:
1) Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) and at least one of: ischaemic symptoms, pathologic Q waves on ECG, ECG changes indicative of ischaemia, coronary artery intervention
2) Pathologic findings of an acute MI

268

What are the lipoproteins in order of density?

Chylomicron

269

What is PCSK9 and what mutation of it is significant?

Binds LDLR and promotes its degradation
Loss of function mutation of PCSK9 -> low LDL

270

How is PCSK9 clinically useful?

Novel form of LDL-lowering therapy is anti-PCSK9 Mab

271

Why is lipoprotein (a) clinically significant?

Risk factor for cardiovascular disease - treat with nicotinic acid

272

What are the forms of primary hypercholesterolaemia and what mutations are involved?

Familial hypercholesterolaemia (type II) - autosomal dominant (LDLR, apoB, PCSK9) or autosomal recessive (LDLRAP1)
Polygenic hypercholesterolaemia - several polymorphisms
Familial hyperalpha0lipoporteinaemia - CETP deficiency
Phyosterolaemia - ABC G5 and G8

273

What are the forms of primary hypertriglyceridaemia and what deficiencies/problems are involved?

Familial type I - lipoprotein lipase or apoC II deficiency
Familial type V - apia V deficiency (sometimes)
Familial type IV - increased synthesis of triglyceride

274

What are the forms of primary mixed hyperlipidaemia?

Familial combined hyperlipidaemia
Familial dysbetalipoproteinaemia
Familial hepatic lipase deficiency

275

What are the forms of hypolipidaemia and what deficiencies/problems are involved?

Beta-lipoporteinaemia - MTP deficiency
Hypo-beta-lipoproteinaemia - truncated apoB protein
Tangier disease - HDL deficiency
Hypoalpha-lipoproteinaemia - apoA-1 mutations (sometimes)

276

Vitamin A
What's another name for it?
What happens in deficiency?
What happens in excess?
How do you test for it?

Retinol
Deficiency - colour blindness
Excess - exfoliation, hepatitis
Test - serum

277

Vitamin D
What's another name for it?
What happens in deficiency?
What happens in excess?
How do you test for it?

Cholecalciferol
Deficiency - osteomalacia/rickets
Excess - hypercalcaemia
Test - Serum

278

Vitamin E
What's another name for it?
What happens in deficiency?
How do you test for it?

Tocopherol
Deficiency - anaemia, neuropathy,?malignancy, IHD
Test - serum

279

Vitamin K
What's another name for it?
What happens in deficiency?
How do you test for it?

Phytomenadione
Deficiency - defective clotting
Test - PTT

280

What are the fat soluble vitamins?

A, D, E, K

281

What are the water soluble vitamins?

B1, B2, B6, B12, C, folate, B3

282

Vitamin B1
What's another name for it?
What happens in deficiency?
How do you test for it?

Thiamin
Deficiency - beri-beri, neuropathy, Wernicke syndrome
Test - RBC transketolase

283

Vitamin B2
What's another name for it?
What happens in deficiency?
What happens in excess?
How do you test for it?

Riboflavin
Deficiency - glossitis
Test - RBC glutathione reductase

284

Vitamin B6
What's another name for it?
What happens in deficiency?
What happens in excess?
How do you test for it?

Pyridoxine
Deficiency - dermatitis/anaemia
Excess - neuropathy
Test: RBC AST activation

285

Vitamin B12
What's another name for it?
What happens in deficiency?
How do you test for it?

Cobalamin
Deficiency - pernicious anaemia
Test - serum B12

286

Vitamin C
What's another name for it?
What happens in deficiency?
What happens in excess?
How do you test for it?

Ascorbate
Deficiency - scurvy
Excess - renal stones
Test - plasma

287

Folate
What happens in deficiency?
How do you test for it?

Deficiency: megaloblastic anaemia, neural tube defect
Test: RBC folate

288

Vitamin B3
What's another name for it?
What happens in deficiency?

Niacin
Deficiency: pellagra - 3 D's:
Dementia
Dermatitis
Diarrhoea

289

Iron
What happens in deficiency?
What happens in excess?
How do you test for it?

Deficiency - hyochromic anaemia
Excess - haemochromatosis
Test: FBC, Fe, ferritin

290

Iodine
What happens in deficiency?
How do you test for it?

Deficiency: goitre, hypothyroid
Test: TFT

291

Zinc
What happens in deficiency?

Dermatitis

292

Copper
What happens in deficiency?
What happens in excess?
How do you test for it?

Deficiency - anaemia
Excess - Wilson's disease
Test: Cu, caeroplasmin

293

Fluoride
What happens in deficiency?
What happens in excess?

Deficiency - dental caries
Excess - fluorosis

294

Which metabolic disorders are screened for in the UK?

Phenylketonuria
Congenital hypothyroidism
Cystic fibrosis
Sickle cell disease
MCADD

295

What is the problem in phenylketonuria?

Phenylalanine hydroxyls deficiency

296

What causes congenital hypothyroidism and how do you screen for it?

Dysgenesis/agenesis of the thyroid gland
TSH levels to screen

297

What is the main problem in cystic fibrosis and how is it screened for?

Mutation in CFTR -> viscous secretions -> ductal blockates
Immune reactive trypsin to screen
If positive, DNA mutation detection

298

What is MCADD and how do you screen for it?

Medium chain acyl CoA dehydrogenase deficiency - a fatty acid oxidation disorder
Acylcarnitine levels by tandem mass spectrometry to screen

299

How are the urea cycle disorders inherited?

Autosomal recessive except for ornithine transcarbamylase deficiency - X linked

300

What are the red flags for urea cycle disorders?

Vomiting without diarrhoea
Hyperammonia and respiratory alkalosis
Encephalopathy
Change in diet

301

What is the treatment for urea cycle disorders?

Remove ammonia
Reduce ammonia production

302

What are the organic acidurias?

Group of metabolic disorders that disrupt amino acid metabolism, particularly branched chain amino acids (leucine, isoleucine and valine)

303

How do organic acidurias present in neonates?

Unusual odours
Lethargy
Feeding problems
Truncal hypotonia
Limb hypertonia
Myoclonic jerks

304

What is seen on blood tests in organic acidurias?

Hyper ammonia with metabolic acidosis and high anion gap (not lactate)
Hypocalcaemia, neutropenia, thrombocytopenia, pancytopenia

305

Other than as a neonate, how might an organic aciduria present?

As a chronic intermittent form with recurrent episodes of:
Ketoacidotic coma
Cerebral abnormalities
Reye syndrome

306

What are the features of Reye syndrome?

Vomiting, lethargy, confusion, seizures, decerebration, respiratory arrest

307

What are the triggers for Reye syndrome?

Salicylates, antiemetics, valproates

308

What is the most common kind of galactosaemia and what does it do?

Galactose-1-phosphate uridylyltransferase deficiency (Gal-1-PUT) is the most severe of the 3 known disorders, in which raised Gal-1-PUT causes liver and kidney disease

309

How does Gal-1-PUT deficiency present?

Vomiting
Diarrhoea
Conjugated hyperbilirubinaemia
Hepatomegaly
Hypoglycaemia
Sepsis

310

What lab investigations should you do in Gal-1-PUT deficiency?

Urine reducing substances
Red cell Gal-1-PUT

311

What are the common features of the glycogen storage disorders?

Result from defects in glycogen synthesis or breakdown. Commonly have muscular, liver, and other consequences. All are due to enzyme deficiencies.

312

How many glycogen storage disorders are there?

11

313

What causes glycogen storage disorder type 1 and what's another name for it?

Von Gierke's disease - glucose-6-phosphatase deficiency

314

What is the pathology in GSD Type I?

Excessive glycogen storage but also prevents glucose export from gluconeogenetic organs

315

How does GSD type I present?

Lactic acidosis
Convulsions
Hypoglycaemia: irritability, pallor, cyanosis, hypotonia, tremors, loss of consciousness, apnoea
Hepatomegaly
Hyperlipidaemia
Hyperuricaemia
Neutropenia

316

What is the pathophysiology in lysosomal storage diseases?

Intraorganelle substrate accumulation leading to organomegaly and consequent dysmorphia and regression

317

What lab investigations should you do in lysosomal storage diseases?

Urine mucopolysaccharides and oligosaccharides
Leucocyte enzyme activity

318

What is the treatment for lysosomal storage diseases?

Bone marrow transplant
Exogenous enzymes

319

What are perioxisomal disorders?

A disorder in the metabolism of very long chain fatty acids and biosynthesis of complex phospholipids

320

What is the neonate profile of perioxisomal disorders?

Severe muscular hypotonia, seizures
Hepatic dysfunction - mixed hyperbilirubinaemia
Dysmorphic signs

321

What is the infant profile of perioxisomal disorders?

Retinopathy (often leading to early blindness)
Sensorineural deafness
Mental deficiency
Hepatic dysfunction
Large fontanelle, osteopenia of long bones, calcified stippling

322

What lab investigation should you do for perioxisomal disorders?

Very long chain fatty acids

323

What is the general pathology in mitochondrial disorders?

Defective ATP production leads to multi system disease especially affecting organs with a high energy requirement e.g. brain, muscle, kidney, retina, and endocrine organs

324

What are the features of Barth syndrome?

Presents at birth
Cardiomyopathy
Neutropenia
Myopathy

325

What are the features of MELAS?

5-15 years
Mitochondrial encephalopathy, lactic acidosis, and stroke like episodes

326

What are the features of Kearns-Sayre?

12-30 years
CPEO
Retinopathy
Deafness
Ataxia

327

What are the causes of hyperglycaemia?

Corticotrophin
Somatotrophin: those with gigantism and acromegaly are at vastly increased risk of contracting T2DM
Catecholaminergic
Secondary to increased insulin resistance or absolute deficiency

328

How common is diabetes in the UK?

About 2 million - 90% T2DM

329

What makes a diagnosis of diabetes mellitus?

Typical symptoms plus
Fasting glucose >7, oral glucose tolerance test >11.1, or random glucose >11.1 OR
Without symptoms but with 2 of the above tests
NICE recommends HbA1c >48 as one of these tests

330

What glucose test results are classed as impaired glucose tolerance?

Random or oral glucose tolerance test >7.8 but

331

What glucose test result counts as impaired fasting glucose?

Fasting glucose >6.1 but

332

What is the difference in risk between impaired glucose tolerance, impaired fasting glucose, and diabetes?

IGT and IFG have the same microvascular risks as WHO classified diabetes but microvascular complications are seen more frequently in diabetics

333

What are the causes of hyperinsulinaemic hypoglycaemia?

Iatrogenic insulin, sulfonylurea excess, insulinoma

334

What are the causes of hypoinsulinaemic hypoglycaemia with positive ketones?

Alcohol binge with no food, pituitary insufficiency, Addison's, liver failure

335

What are the causes of hypoinsulinaemic hypoglycaemia with negative ketones?

Non-pancreatic neoplasms: fibrosarcomata, fibromata

336

What are some causes of hypoglycaemia in adults with low insulin and low C peptide?

Fasting
Strenuous exercise
Critical illness
Endocrine deficiency (hypopituitarism, adrenal failure)
Liver failure
Anorexia nervosa

337

What are some causes of hypoglycaemia in neonates?

Ketones present, FFA present: premature, IUGR, comorbidity
Ketones absent, FFA present: inherited metabolic disorder

338

What are the features of non-islet tumour hypoglycaemia?

Low glucose, low insulin, low C-peptide, low FFA, low ketones
Tumours that cause a paraneoplastic syndrome, secreting, 'big IGF-2' which binds to IGF-1 and insulin receptors

339

What are some of the common problems in low birth weight neonates?

Respiratory distress syndrome
Retinopathy of prematurity
Intraventricular haemorrhage
Patent ductus arterioles
Necrotising enterocolitis

340

What are some of the differences in renal function in children as opposed to adults?

Functional maturity of GFR by 2 years but low GFR for surface area. Less reabsorption than adult due to short proximal tubule (but usually adequate for small filtered load). Reduced concentrating ability due to shop troops of Henle and distal collecting ducts. Persistent sodium loss due to distal tubule being relatively aldosterone-insensitive

341

Why do children have a high insensible water loss?

High surface area
High skin blood flow
High metabolic/respiratory rate
High transepidermal fluid loss

342

What are some causes of hypernatraemia specific to neonates?

Intraventricular haemorrhage
Sodium bicarbonate when treating acidosis

343

When does hypernatraemia become uncommon in paediatrics?

After 2 weeks - usually associated with dehydration

344

What defines 'prolonged' neonatal jaundice?

>14 days if term or >21 days in preterm

345

What kind of hyperbilirubinaemia is always pathological in neonates?

Conjugated

346

What is a normal GFR?

120ml/hr

347

How does GFR change with age?

Age related decline of ~1ml/hr/year

348

Define 'clearance' in relation to renal function

The volume of plasma that can be completely clear of a marker substance in a unit of time

349

When does clearance = GFR?

Marker is not bound to serum proteins AND is freely filtered by the glomerulus AND is not secreted/absorbed by tubular cells

350

What ist he gold standard measure of GFR and why isn't it used?

Inulin - but requires a steady state infusion and difficult to assay, so reserved for research purposes only

351

What marker is used in clinical practice to measure renal function and how do we measure it?

Creatinine
Very variable between individuals so we use it to monitor trends over time
Different equations use serum creating with variable combinations of age, weight, sex, ethnicity to estimate GFR

352

What do you use a single sample of urine for?

Dipstick testing
Microscopic examination
Proteinuria quantification (protein:creatinine ratio)

353

What can you use a 24h urine collection for?

Proteinuria quantification (now usually do protein:creatinine ratio instead)
Creatinine clearance estimation
Electrolyte estimation
Stone forming elements

354

What ca you see on urine microscopy?

Crystals
RBCs
WBCs
Casts
Bacteria

355

What are the 3 kinds of acute kidney injury?

Pre renal - reduced renal perfusion with no structural abnormality

Renal: vascular, glomerular, tubular, interstitial

Post-renal: obstruction to urinary flow

356

Describe stage 1 chronic kidney disease, its GFR, and its prevalence

Kidney damage with normal GFR
>90 GFR
3.3% prevalence

357

Describe stage 2 chronic kidney disease, its GFR, and its prevalence

Mildly decreased GFR
60-89 = GFR
3% prevalence

358

Describe stage 3 chronic kidney disease, its GFR, and its prevalence

Moderately decreased GFR
30-59 = GFR
4.3% prevalence

359

Describe stage 4 chronic kidney disease, its GFR, and its prevalence

Severely decreased GFR
15-29 = GFR
0.2% prevalence

360

Describe stage 5 chronic kidney disease, its GFR, and its prevalence

End stage kidney failure
GFR

361

What are the commonest causes of chronic kidney disease?

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

362

What are the consequences of chronic kidney disease?

Progressive failure of homeostatic function (acidosis, hyperkalaemia)
Progressive failure of hormonal function (anaemia, renal bone disease)
Cardiovascular disease (vascular calcification, uraemic cardiomyopathy)
Uraemia and death