ChemPath Flashcards
(362 cards)
1
Q
What % of the body is water?
A
60%
2
Q
What is the ratio of fluid in the body in terms of intracellular:extracellular?
A
2:1
3
Q
Which compartments make up the body’s extracellular fluid?
A
-Intravascular-Interstitial-Transcellular
4
Q
What is the function of interstitial fluid?
A
Bathes cells + makes up the largest component of ECF
5
Q
What is transcellular fluid/where is it?
A
Within epithelial lined spaces e.g. CSF, joint fluid, bladder urine, aqueous humour
6
Q
What is osmolality?
A
The total number of particles in a solution
7
Q
What are the units for osmolality?
A
mmol/kg
8
Q
What is osmolarity?
A
2(Na + K) + urea + glucose
9
Q
What are the units of osmolarity?
A
mmol/L
10
Q
What are the determinants of osmolarity?
A
Physiological: sodium, potassium, chlorine, HCO3, urea, glucosePathological: endogenous (e.g. glucose), exogenous (e.g. ethanol, mannitol)
11
Q
What is the osmolar gap?
A
The difference between osmolarity and osmolality
12
Q
What is the normal range for osmolality?
A
275-295 mmol/kg
13
Q
What is the normal range for sodium?
A
135-145 mmol/L
14
Q
How much sodium is freely exchangeable and where is the rest of it?
A
70% - rest is complexed in bone
15
Q
Is sodium predominantly intracellular or extracellular?
A
Extracellular
16
Q
What maintains sodium levels?
A
Active pumping from ICF to ECF by Na+/K+ ATPase
17
Q
Which fluid volume directly depends on sodium?
A
ECF
18
Q
How should you manage mild hyponatraemia?
A
Treat the underlying cause not the sodium level provided it’s not severe
19
Q
What are the features of symptomatic hyponatraemia?
A
-Nausea and vomiting (
20
Q
What measure should you use to determine if someone has true hyponatraemia?
A
Osmolality
21
Q
What might be the cause of hyponatraemia if serum osmolality is high?
A
Glucose/mannitol infusion
22
Q
What might be the cause of hyponatraemia if serum osmolality is normal?
A
Spurious - drip arm samplePseudohyponatraemia: hyperlipidaemia, paraproteinaemia
23
Q
What might be the cause of hyponatraemia if serum osmolality is low?
A
True hyponatraemia
24
Q
What is TURP syndrome?
A
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?
ThirstConfusionSeizures and ataxiaComa
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, diarrhoeaSkin loss: excessive sweating, burnsRenal 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: tachypnoeaSkin loss: excessive sweating, feverRenal loss: diabetes insipidusMisc: 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 traumaTumourSurgery
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?
InheritedLithiumChronic 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 intakeTranscellular movement (ICF>ECF)Decreased excretion
69
What are some causes of excessive potassium intake?
Oral (fasting)ParenteralStored blood transfusion
70
What are some causes of transcellular movement of potassium?
AcidosisInsulin shortageTissue 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)NSAIDsACEI
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 pHLow bicarbNormal CO2 or low if compensated
78
What is the pH, bicarb and CO2 in metabolic alkalosis?
High pHHigh bicarbNormal CO2 or high if compensated
79
What is the pH, bicarb and CO2 in respiratory acidosis?
Low pHNormal bicarb or high if compensatedHigh CO2
80
What is the pH, bicarb and CO2 in respiratory alkalosis?
High pHNormal bicarb or low if compensatedLow CO2
81
What are the causes of metabolic acidosis?
Lactate build upDKARenal tubular acidosis
82
What are the causes of metabolic alkalosis?
Pyloric stenosisHypokalaemia
83
What are the causes of respiratory acidosis?
Lung injury - pneumonia, COPDDecreased ventilation
84
What are the causes of respiratory alkalosis?
Mechanical ventilationAnxiety/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?
KULTKetoacidosis (DKA, alcoholic, starvation)Uraemia (renal failure)Lactic acidosisToxins (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?
ALTASTAlk phosGGTBilirubin
99
What are the LFT markers of liver synthetic function?
Clotting (INR)AlbuminGlucose
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 painSeizuresPsych disturbancesNausea and vomitingTachycardiaHypertensionSensory lossMuscle weaknessConstipationUrinary 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 factorsAnalgesiaIV 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 lesionsRaised porphyrins in faeces or urine
119
Which non-acute porphyrias have skin lesions only?
Congenital erythropoietic porphyriaErythropoietic protoporphyriaPorphyria cutanea tarda
120
What are the features of erythropoietic protoporphyria?
PhotosensitivityBurning, 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 coproporphyrinsIncreased 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 diseaseEpilepsyUntreated hypothyroidism (impairs the GH and cortisol responses)
132
What are the side effects of doing a combined pituitary function test?
Sweating, palpitations, loss of consciousnessRarely: convulsions with hypoglycaemiaWith 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 testThyrotrophin releasing hormone testGonadotrophin releasing hormone test
134
How do you interpret the insulin tolerance test?
Adequate cortisol response: increase from >170 nmol/L to >500 nmol/LAdequate 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 gonadotrophinFemale - 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 goitrePostpartum 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 hypothyroidismHashimoto'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?
PapillaryFollicularMedullaryLymphomaAnaplastic
173
What are the features of papillary thyroid cancer?
>60% cases30-40 years oldSurgery +/- radioiodineThyroxine to lower TSH
174
What are the features of follicular thyroid cancer?
25%Middle agedWell differentiated but spreads earlySurgery + radioiodine + thyroxine
175
What are the features of medullary thyroid cancer?
5% originates in parafollicular cellsLinked to MEN2Produce calcitonin
176
What are the features of lymphoma thyroid cancer?
5% MALT originRisk factor: chronic HashimotosGood prognosis
177
What are the features of anaplastic thyroid cancer?
RareElderlyPoor 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?
AutoimmuneTBTumour depositsAdrenal haemorrhageAmyloid 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 faceBuffalo humpStriae, acneHypertensionDiabetesMuscle weakness (proximal myopathy)Hirsutism
183
What are the symptoms and signs of Addison's?
High potassiumLow sodium and glucosePostural hypotensionSkin pigmentationLethargyDepression
184
What are the symptoms and signs of Conn's?
Uncontrollable hypertensionHigh sodiumLow potassium
185
What are the symptoms and signs of phaeo?
HypertensionArrhythmiasDeath if untreated
186
What investigations should you do in Cushing's?
Low dose dexamethasoneHigh dose dexamethasoneCortisol 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 blockadeBeta blockadeThen 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?
ArrhythmiasHeart blockConfusionXanthopsia (seeing yellow)
196
What are the signs of lithium toxicity?
Tremor (early)LethargyFitsArrhythmiaRenal failure
197
What are the signs of gentamicin toxicity?
TinnitusDeafnessNystagmusRenal failure
198
What are the signs of theophylline toxicity?
ArrhythmiasAnxietyTremorConvulsions
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 hypokalaemiaReduce 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 active50% bound to albumin, therefore affected by albumin level (use corrected calcium)
216
What are the two main hormones in calcium metabolism?
PTH1,25 (OH)2 D - calcitriol
217
What are the actions of PTH?
Increases tubular 1alpha hydroxylation of bit DMobilises calcium from boneIncreases renal calcium reabsorptionIncreases renal phosphate excretion
218
What are the actions of calcitriol?
Increases calcium and phosphate absorption from the gutBone 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 PTHPrimary: DiGeorge syndromeSecondary: 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 - dehydrationIf 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 turnoverBone metastasisThyrotoxicosisSarcoidosis (increased 1alphaOH)
239
If a patient is hypercalcaemic with low/normal albumin, high phosphate and normal ALP what might the cause be?
MyelomaExcess vitamin DSarcoidMilk alkali syndrome (and increased bicarbonate)
240
What are the symptoms of hypercalcaemia?
Stones (renal)Bones (pain)Groans (psych)Moans (abdo pain)PolyuriaMuscle weakness
241
How should you treat hypercalcaemia?
Correct dehydrationBisphosphonatesCorrect 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 diseaseHypoparathyroidism (including post thyroid surgery)PseudohypoparathyroidismHypomagnesaemia
244
What are the causes of hypocalcaemia with normal/low phosphate?
OsteomalaciaAcute pancreatitisOver hydrationRespiratory 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 paraesthesiaCarpopedal spasmNeuromuscular excitability (Trousseau's and Ckvostek's sign)
247
What's the treatment for hypocalcaemia?
Mild: give calciumChronic kidney disease: alfacalcidolSevere: 10% calcium gluconate IV
248
What are the risk factors for renal stones?
DehydrationAbnormal urine pH (meat intake, renal tubular acidosis)Increased excretion of stone constituentsUrine infectionAnatomical abnormalities
249
What are the causes of calcium stones?
Most patients are normocalcaemicResults from:-Hyperoxaluria: increased intake/absorption etc-Hypercalciuria: increased intake/renal leak
250
How are calcium stones managed preventatively?
Avoid dehydrationReduce oxalate intakeMaintain Ca intakeThiazides -> hypocalciuricCitrate (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 analysisSpot urine: pH, MCS, amino acids, albumin24h 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 muscleCK-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 spurtPathological: ->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 intervention2) 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 degradationLoss 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 polymorphismsFamilial hyperalpha0lipoporteinaemia - CETP deficiencyPhyosterolaemia - 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 deficiencyFamilial type V - apia V deficiency (sometimes)Familial type IV - increased synthesis of triglyceride
274
What are the forms of primary mixed hyperlipidaemia?
Familial combined hyperlipidaemiaFamilial dysbetalipoproteinaemiaFamilial hepatic lipase deficiency
275
What are the forms of hypolipidaemia and what deficiencies/problems are involved?
Beta-lipoporteinaemia - MTP deficiencyHypo-beta-lipoproteinaemia - truncated apoB proteinTangier disease - HDL deficiencyHypoalpha-lipoproteinaemia - apoA-1 mutations (sometimes)
276
Vitamin AWhat's another name for it?What happens in deficiency?What happens in excess?How do you test for it?
RetinolDeficiency - colour blindnessExcess - exfoliation, hepatitisTest - serum
277
Vitamin DWhat's another name for it?What happens in deficiency?What happens in excess?How do you test for it?
CholecalciferolDeficiency - osteomalacia/ricketsExcess - hypercalcaemiaTest - Serum
278
Vitamin EWhat's another name for it?What happens in deficiency?How do you test for it?
TocopherolDeficiency - anaemia, neuropathy,?malignancy, IHDTest - serum
279
Vitamin KWhat's another name for it?What happens in deficiency?How do you test for it?
PhytomenadioneDeficiency - defective clottingTest - 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 B1What's another name for it?What happens in deficiency?How do you test for it?
ThiaminDeficiency - beri-beri, neuropathy, Wernicke syndromeTest - RBC transketolase
283
Vitamin B2What's another name for it?What happens in deficiency?What happens in excess?How do you test for it?
RiboflavinDeficiency - glossitisTest - RBC glutathione reductase
284
Vitamin B6What's another name for it?What happens in deficiency?What happens in excess?How do you test for it?
PyridoxineDeficiency - dermatitis/anaemiaExcess - neuropathyTest: RBC AST activation
285
Vitamin B12What's another name for it?What happens in deficiency?How do you test for it?
CobalaminDeficiency - pernicious anaemiaTest - serum B12
286
Vitamin CWhat's another name for it?What happens in deficiency?What happens in excess?How do you test for it?
AscorbateDeficiency - scurvyExcess - renal stonesTest - plasma
287
FolateWhat happens in deficiency?How do you test for it?
Deficiency: megaloblastic anaemia, neural tube defectTest: RBC folate
288
Vitamin B3What's another name for it?What happens in deficiency?
NiacinDeficiency: pellagra - 3 D's: DementiaDermatitisDiarrhoea
289
IronWhat happens in deficiency?What happens in excess?How do you test for it?
Deficiency - hyochromic anaemiaExcess - haemochromatosisTest: FBC, Fe, ferritin
290
IodineWhat happens in deficiency?How do you test for it?
Deficiency: goitre, hypothyroidTest: TFT
291
ZincWhat happens in deficiency?
Dermatitis
292
CopperWhat happens in deficiency?What happens in excess?How do you test for it?
Deficiency - anaemiaExcess - Wilson's diseaseTest: Cu, caeroplasmin
293
FluorideWhat happens in deficiency?What happens in excess?
Deficiency - dental cariesExcess - fluorosis
294
Which metabolic disorders are screened for in the UK?
PhenylketonuriaCongenital hypothyroidismCystic fibrosisSickle cell diseaseMCADD
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 glandTSH levels to screen
297
What is the main problem in cystic fibrosis and how is it screened for?
Mutation in CFTR -> viscous secretions -> ductal blockatesImmune reactive trypsin to screenIf 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 disorderAcylcarnitine 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 diarrhoeaHyperammonia and respiratory alkalosisEncephalopathyChange in diet
301
What is the treatment for urea cycle disorders?
Remove ammoniaReduce 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 odoursLethargyFeeding problemsTruncal hypotoniaLimb hypertoniaMyoclonic 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 comaCerebral abnormalitiesReye 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?
VomitingDiarrhoeaConjugated hyperbilirubinaemiaHepatomegalyHypoglycaemiaSepsis
310
What lab investigations should you do in Gal-1-PUT deficiency?
Urine reducing substancesRed 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 acidosisConvulsionsHypoglycaemia: irritability, pallor, cyanosis, hypotonia, tremors, loss of consciousness, apnoeaHepatomegalyHyperlipidaemiaHyperuricaemiaNeutropenia
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 oligosaccharidesLeucocyte enzyme activity
318
What is the treatment for lysosomal storage diseases?
Bone marrow transplantExogenous 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, seizuresHepatic dysfunction - mixed hyperbilirubinaemiaDysmorphic signs
321
What is the infant profile of perioxisomal disorders?
Retinopathy (often leading to early blindness)Sensorineural deafnessMental deficiencyHepatic dysfunctionLarge 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 birthCardiomyopathyNeutropeniaMyopathy
325
What are the features of MELAS?
5-15 yearsMitochondrial encephalopathy, lactic acidosis, and stroke like episodes
326
What are the features of Kearns-Sayre?
12-30 yearsCPEORetinopathyDeafnessAtaxia
327
What are the causes of hyperglycaemia?
CorticotrophinSomatotrophin: those with gigantism and acromegaly are at vastly increased risk of contracting T2DMCatecholaminergicSecondary 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 plusFasting glucose >7, oral glucose tolerance test >11.1, or random glucose >11.1 ORWithout symptoms but with 2 of the above testsNICE 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?
FastingStrenuous exerciseCritical illnessEndocrine deficiency (hypopituitarism, adrenal failure)Liver failureAnorexia nervosa
337
What are some causes of hypoglycaemia in neonates?
Ketones present, FFA present: premature, IUGR, comorbidityKetones 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 ketonesTumours 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 syndromeRetinopathy of prematurityIntraventricular haemorrhagePatent ductus arteriolesNecrotising 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 areaHigh skin blood flowHigh metabolic/respiratory rateHigh transepidermal fluid loss
342
What are some causes of hypernatraemia specific to neonates?
Intraventricular haemorrhageSodium 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?
CreatinineVery variable between individuals so we use it to monitor trends over timeDifferent 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 testingMicroscopic examinationProteinuria 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 estimationElectrolyte estimationStone forming elements
354
What ca you see on urine microscopy?
CrystalsRBCsWBCsCastsBacteria
355
What are the 3 kinds of acute kidney injury?
Pre renal - reduced renal perfusion with no structural abnormalityRenal: vascular, glomerular, tubular, interstitialPost-renal: obstruction to urinary flow
356
Describe stage 1 chronic kidney disease, its GFR, and its prevalence
Kidney damage with normal GFR>90 GFR3.3% prevalence
357
Describe stage 2 chronic kidney disease, its GFR, and its prevalence
Mildly decreased GFR60-89 = GFR3% prevalence
358
Describe stage 3 chronic kidney disease, its GFR, and its prevalence
Moderately decreased GFR30-59 = GFR4.3% prevalence
359
Describe stage 4 chronic kidney disease, its GFR, and its prevalence
Severely decreased GFR15-29 = GFR0.2% prevalence
360
Describe stage 5 chronic kidney disease, its GFR, and its prevalence
End stage kidney failureGFR
361
What are the commonest causes of chronic kidney disease?
DiabetesAtherosclerotic renal diseaseHypertensionChronic glomerulonephritisInfective or obstructive uropathyPolycystic 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
