Chem path Flashcards
1
Q
Osmolarity formula
A
2(Na + K) + urea + glucose
2
Q
Units for osmolality and osmolarity
A
Osmolality = mmol/kg Osmolarity = mmol/l
3
Q
Normal sodium range
A
135-145 mmol/l
4
Q
Symptoms if sodium is <117 mmol/l
A
Coma -> death
Symptomatic = medical emergency
If compensated, rarely emergency, even if 110-120 and asymptomatic. More dangerous to correct too fast.
5
Q
Causes of reported hyponatraemia if the serum osmolality is high, normal, and low.
A
High - glucose/mannitol infusion
Normal - spurious, drip arm sample, hyperlipidaemia
Low - true hyponatraemia
6
Q
What is TURP syndrome?
A
- Irrigation of bladder with Glycine 1.5% during transurethral resection of prostate
- Absorption of fluids into prostatic venous sinuses
- Hyponatraemia
7
Q
Urinary sodium level if renal or non-renal cause of hyponatraemia (when hypo/hypervolaemic)
A
Renal >20 mmol/l
Non-renal <20 mmol/l
8
Q
Urinary sodium in euvolaemic hyponatraemia
A
> 20 mmol/l
9
Q
Causes of renal hypovolaemic hyponatraemia
A
Diuretics
Addison’s
Salt-losing nephropathies - kidney can’t reabsorb sodium, so water is lost too
10
Q
Causes of non-renal hypovolaemic hyponatraemia
A
Vomiting
Diarrhoea
Excess sweating
Third spaces losses (ascites, burns)
Kidney holding onto sodium, so low urinary sodium, but still overall loss of sodium
11
Q
Causes of euvolaemic hyponatraemia
A
SIADH - water retention, but not sodium retention (so high urinary sodium)
Severe hypothyroidism
Glucocorticoid deficiency
12
Q
Normal range for serum osmolality
A
275-295 mmol/kg
13
Q
Causes of renal hypervolaemic hyponatraemia
A
AKI
CKD
14
Q
Causes of non-renal hypervolaemic hyponatraemia
A
Cardiac failiure
Cirrhosis
Inappropriate IV fluid
15
Q
What is important to do before measuring urinary sodium in someone on diuretics?
A
Stop diuretics
Diuretics affect urinary sodium and not give accurate reflection of patient’s state
16
Q
How does cirrhosis lead to hyponatraemia?
A
- Poor breakdown of vasodilators (NO)
- Low blood pressure
- ADH release - water retention
- Diluted sodium
(Similar in HF - but BNP/ANP are natriuretic (excretion of sodium) and thought to worsen hyponatraemia too)
17
Q
Management of hypovolaemic hyponatraemia
A
- Treat the cause e.g. antiemetics
* Supportive - replace fluid slowly, regularly check sodium
18
Q
Management of euvolaemic hyponatraemia
A
- SIADH - fluid restriction and treat the cause (demeclocycline and tolvaptan can induce state of diabetes insipidus)
- Hypothyroidism - levothyroxine
- Addison’s - hydrocortisone +/- fludrocortisone
19
Q
Management of hypervolaemic hyponatraemia
A
- Fluid restrict +/- diuresis
* Cirrhosis - specialist input
20
Q
What can rapid correction of hyponatraemia lead to and how does it present?
How quickly should you correct sodium?
A
Central pontine myelinolysis
• Pseudobulbar palsy
• Paraparesis
• Locked-in syndrome
Aim to increase Na+ by no more than 8-10 mmol per 24 hours
21
Q
How can surgery lead to hyponatraemia?
A
Overhydration with hypotonic IV fluids
Transient increase in ADH (water retention) due to stress of surgery i.e. SIADH
22
Q
Diagnosis of SIADH
A
Exclusion • High urine osmolarity • Clinically euvolaemic • Normal 9am cortisol • Normal TFTs
23
Q
Most common malignancy and drugs causing SIADH
A
- Malignancy - small cell lung cancer
* Drugs e.g. carbamazepine, SSRIs
24
Q
How does tolvaptan work?
A
Reduces channel sensitivity to ADH in collecting duct
25
Causes of hypovolaemic hypernatraemia
Vomiting
Diarrhoea
Excessive sweating
Burns
Renal loss
• Loop diuretics
• Osmotic diuresis (glucose, mannitol)
• Diabetes insipidus - more likely euvolaemic
26
Causes of euvolaemic hypernatraemia
Respiratory (tachypnoea)
Skin (sweating, fever)
Renal (diabetes insipidus)
27
Causes of hypervolaemic hypernatraemia
Mineralocorticoid excess (Conn's syndrome - too much sodium retention and potassium excretion)
Inappropriate saline
28
Management of hypernatraemia
Slow fluids - even saline, but this can cause initial rise in sodium before it falls
Encourage PO!
29
Urine : plasma osmalality ratio in diabetes inspidus and reason
< 2
| Urine is dilute despite concentrated plasma
30
Types of diabetes inspidus and causes
```
Cranial - lack of/no ADH
• Surgery
• Pituitary radiation
• Trauma
• Tumours
```
```
Nephrogenic
• Receptor insensitivity to ADH
• Inherited channelopathies
• Lithium
• Hypercalcaemia
```
31
Treatment of nephrogenic diabetes insipidus
Thiazide diuretics
32
What 3 things should be excluded in patients with diabetes inspidus first?
Diabetes mellitus
Hypokalaemia
Hypercalcaemia
These can cause resistance to ADH causing a 'nephrogenic diabetes insipidus'
33
Diagnosis of diabetes insipidus and the meaning of different results
8 hour fluid deprivation test
• Normal - urine conc. >600 mOsmol/kg
• Primary polydipsia - urine conc. 400-600 (psychogenic, schizophrenia, cancer)
• Cranial - urine concentrates after desmopressin
• Nephrogenic - urine does not concentrate even after desmopressin
34
What is the primary intracellular cation and what is the normal blood range?
Potassium
3.5-5.5 mmol/l
35
Causes of hypokalaemia
GI loss
Renal loss
• hyperaldosterism (consider if high Na, low K)
• Thiazide and loop diuretics
• Osmotic diuresis
Redistribution into cells
• Insulin
• Beta-agonists
• Metabolic alkalosis (cells pump out H+, K+ goes in)
Rare causes
• Tubular acidosis
• Hypomagnesaemia
36
Outline renal tubular acidosis type 1, type 2, and type 4.
Type 1
• Most severe
• Distal failure of H+ excretion into renal lumen, subsequent acidosis and hypokalaemia (can't be reabsorbed)
Type 2
• Milder
• Proximal failure to reabsorb bicarbonate
• Acidosis and hypokalaemia (increased flow rate to distal tubule, increased K excretion)
Type 4
• Aldosterone deficiency/resistance
• Acidosis and HYPERkalaemia
37
Features of hypokalaemia
Muscle weakness
Cardiac arrhythmias
Polyuria and polydipsia
38
Hypokalaemia treatment
oral SandoK
If lower than 3.0, consider IV potassium chloride
39
Why should IV potassium chloride not be administered >10mM/hr
Risk of arrhythmia
40
Causes of hyperkalaemia
```
Excessive intake
Transcellular movement
• Acidosis
Decreased excretion
• Acute renal failure
• Spironolactone
• Addison's
```
41
What should be considered when assessing for hyperkalaemia?
* Repeat sampling - spurious result due to haemolysed blood
* ECG
* VBG - acidosis?
42
ECG changes associated with hyperkalaemia
Loss of P waves
Tall tented T waves
Widened QRS
ECG is "pulled apart" to create a 'sine wave' if left untreated
43
When should you treat hyperkalaemia
>5.5 + ECG changes
>6.5
44
Hyperkalaemia treatment
1. 10ml 10% calcium gluconate (cardioprotection)
2. 100ml 20% dextrose + 10U short-acting insulin e.g. actrapid
3. Salbutamol adjunct
4. Treat cause
45
When should you be careful with administration of IV calcium?
Patients on Digoxin
| Cardiac monitoring as it can precipitate arrhythmias
46
Normal pH range
7.35 - 7.45
47
Normal CO2 range
4.7 - 6kPa
48
Normal bicarbonate range
22 - 30mmol/l
49
Normal O2 range
10 - 13kPa
50
Causes of metabolic acidosis
Elevated anion gap:
• Lactic acidosis e.g. in metformin OD
• Ketoacidosis e.g. DKA, alcoholic
• Toxins e.g. methanol
Intestinal fistula
51
Causes of respiratory acidosis
Pneumonia
COPD
Decreased ventilation e.g. morphine OD
52
Causes of metabolic alkalosis
Pyloric stenosis
Hypokalaemia
Diuretics
53
Causes of respiratory alkalosis
Mechnical ventilation
Panic attack
Aspirin OD (mixed with metabolic acidosis)
54
What is the anion gap, how do you calculate it, and what is the normal range?
Difference between cations and anions
Concentration of unmeasured anions
Almost all albumin
(Na + K) - (Cl + HCO3)
14 - 18mmol/l
55
What is the osmolar gap and normal range
Osmalality (measured) - Osmolarity (calculated)
Elevated - presence of abnormal/extra solutes e.g. alcohols, ketones, lactate
<10
56
When can AFP be elevated?
* HCC
* Testicular cancer
* Pregnancy
57
What diagnosis does AST:ALT = 2 support?
Alcoholic hepatitis
58
What diagnosis does AST:ALT = 1 support?
Viral hepatitis
59
When is ALT raised?
When hepatocytes die - more sensitive than AST for hepatocyte damage
60
When is ALP raised?
Cholestasis (intra/extrahepatic)
Bone disease
Pregnancy
61
When is GGT raised and what can it confirm?
Chronic alcohol use
Bile duct disease
Metastasis
Confirms hepatic source of raised ALP
62
AST:ALT and GGT in NAFLD
AST:ALT < 1
| Raised GGT
63
Is low or high albumin common in hospital patients?
Low
Acute illness, systemic inflammation and malnutrition lead to reduced albumin
Poor prognostic factor
64
How is clotting factor function measured?
INR
PT standardised for age and population
65
Is deranged clotting diagnostic of hepatocellular dysfunction on its own?
No
Other aetiologies e.g. warfarin, thrombophilia, DIC
66
Why is the measurement of clotting factors a better marker of acute liver function than albumin?
Shorter half life
Albumin has 20-day half life
67
Where is bilirubin 'conjugated'?
Hepatocytes
68
How and where is conjugated bilirubin further metabolised?
Conjugated bilirubin -> urobilinogen (GI tract)
Some urobilinogen reabsorbed and excreted tin kidneys as urobilin
Rest of urobilinogen -> stercobilin
69
Causes of pre-hepatic jaundice
Haemolysis (increased bilirubin production)
| Congestive heart failure (hepatic congestion)
70
Causes of hepatic jaundice
Liver failure
Gilbert syndrome
Hepatitis
PBC
71
Is conjugated or unconjugated bilirubin raised in hepatic jaundice?
Unconjugated
72
Causes of post-hepatic jaundice
Obstruction of biliary tree e.g. stones, mass (intra or extraluminal), inflammation
73
Is there urobilinogen in post-hepatic jaundice?
No
74
What is there a deficiency of in acute intermittent porphyria?
Hydroxymethylbilane (HMB) synthase
Autosomal dominant
(Build up of ALA and PBG)
75
Symptom groups of acute intermittent porphyria
Neuro-visceral
76
Diagnosis of acute intermittent porphyria
"Port wine urine" - oxidised over night
ALA and PBG in urine
77
Acute intermittent porphyria medication precipitatants
ALA synthase inducers (steroids, ethanol, barbiturates)
78
Treatment for acute intermittent porphyria
Avoid precipitating factors
Analgesia
IV carbohydrate / haem arginate
79
How does hereditary coproporphyria (HCP) and variegate porphyria (VP) present?
Neuro-visceral symptoms
| Skin lesions
80
How does congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) present?
All 3 are non-acute porphyrias - skin lesions
EPP - photosensitivity, burning, itching oedema following sun exposure. Non blistering. In children.
PCT - vesicles on sun exposed sites (cursting, pigmented)
81
What must be measured in erythropoietic protoporphyria (EPP)?
RBC protoporphyrin
82
Diagnosis of porphyria cutaena tarda (PCT)?
Increased urinary uroporphyrins and coproporphyrins
Increased ferritin
Microcytic anaemia
83
Which pituitary hormones does TRH stimulate?
TSH
| Prolactin
84
Which pituitary hormone does dopamine stimulate?
Prolactin
85
What does the combined pituitary function test (CPFT) involve?
Administration of LHRH (GnRH), TRH and insulin
Measure pituitary hormones at 0, 30, 60, 90 and 120 mins
86
Contraindications and side effects of CPFT?
CI - IHD, epilepsy, untreated hypothyroidism
SE - hypoglycaemia, metallic taste with TRH
87
How do you interpret insulin tolerance in the CPFT?
Adequate cortisol and GH response
88
Describe the normal response in CPFT TRH tolerance test
Adequate TSH response, higher at 30mins than 60 mins
Raised prolactin
89
What does inadequate response to GnRH mean in CPFT?
Early indication of hypopituitarism
Not used to measure gonadotrophin deficiency - diagnosed on basal levels
Children should have no response of LH or FSH
90
Difference between pituitary micro and macroadenoma
Micro < 10mm, usually benign
| Macro > 10mm, aggressive
91
How can a non-functioning adenoma increase prolactin levels and how is it treated?
Crush the stalk
Reduced blood flow
Lower dopamine inhibition
Increased prolactin
Small increase compared to prolactinoma
Surgical treatment - bromocriptine/cabergoline won't work
92
What are the posterior pituitary hormones?
ADH
| Oxytocin
93
What can a raised TSH and normal T4 suggest?
Treated hypothyroidism
| Subclinical hypothyroidism
94
What can subclinical hyperthyroidism lead to?
Primary hypothyroidism
95
Findings in sick-euthyroid syndrome
Low T3 and T4 due to acute illness
TSH may start high then become low, or stay normal, TSH may transiently rise above normal during recovery
96
Causes of hyperthyroidism with high uptake on pertechnetate scan
Graves disease
• F > M (9:1)
• Anti-TSH receptor
Toxic multinodular goitre
Toxic adenoma
• Hot nodule
97
Causes of hyperthyroidism with low uptake on pertechnetate scan
Subacute De Quervains thyroiditis
• Self-limiting, post-viral
• Painful goitre
• Initially hyper, then hypothyroid
Postpartum thyroiditis
• Similar to De Quervain's
98
Causes of autoimmune hypothyroidism
Primary atrophic
• Diffuse lymphocytic infiltration and atrophy
• No goitre - small
```
Hashimotos thyroiditis
• Plasma cell infiltration
• Elderly females
• Initial 'Hashitoxicosis'
• Anti-TPO/TG
• Hurthle cells and eosinophilic cytoplasm on histopathology
• Goitre
```
99
Non-autoimmune causes of hypothryoidism
Iodine deficience
Post-thyroidectomy/radioiodine
Drugs e.g. lithium, amiodarone
100
Medical treatement for hyperthyroidism
Symptomatic
• Beta-blockers
• Topical steroids for dermopathy
• Eye drops
Anti-thyroid
• Carbimazole (blocks TPO)
101
Non-medical treatment for hyperthyroidism
Radio-iodine
• Usually after medical has failed
• CI in pregnancy and lactating women
Surgical hemi/total
1. Women intending to become pregnant in next 6 months
2. Local compression e.g. oesophageal
3. Cosmetic
4. Suspected cancer
5. co-hyperparathyroidism
6. Refractory to med
102
What must patients be prior to thyroidectomy
Euthyroid
103
How does a thyroid storm present and how is it treated?
Shock, pyrexia, confusion, vomiting
```
HDU/ITU support
• Cooling
• High dose anti-thyroid meds
• Corticosteroids
• Circulatory and resp support
```
104
What is the most common thyroid neoplasm, its treatment, histological findings and prognosis?
Papillary
Surgery +/- radioiodine
Thyroxine to lower TSH
Psammoma body calcifications on histology
Very good prognosis (although cervical lymph node spread associated with recurrence)
105
What is the problem with follicular thyroid cancer?
Spreads early - blood -> liver / bone
| cold nodules
106
What is a useful tumour marker for thyroid cancer?
Thyroglobulin
107
Where does medullary thyroid cancer originate, what condition is it linked to and what does it produce?
Originates in parafollicular "C" cells
Linked to MEN2
Produces calcitonin
108
What is a risk factor for thyroid lymphoma (majority non-Hodgkin B cell)?
Chronic Hashimotos / chronic lymphocitic thyroiditis
109
Where do thyroid lymphomas originate?
MALT
110
Prognosis in anaplastic thyroid cancer
Poor response to treatment
111
What do the 3 forms of multiple endocrine neoplasias affect?
MEN1 (3Ps)
• Pituitary
• Pancreatic
• Parathyroid
MEN2a (2Ps, 1M)
• Parathyroid
• Phaeochromocytoma
• Medullary thyroid
MEN2b (1P, 2Ms)
• Phaeochromocytoma
• Medullary thyroid
• Mucocutaenous neuromas (and marfanoid)
112
What is Cushing's disease?
Excess ACTH caused by benign pituitary tumour
113
What causes 10% and 5% of Cushing syndrome?
10% - adrenal tumour
| 5% - ectopic ACTH-producing tumour
114
Investigations for Cushing's syndrome
Want to see if cortisol can be suppressed
1. Low dose dexamethasone (0.5mg) - fail to suppress cortisol in all cases
2. High dose dexamethasone (2mg) - suppresses cortisol in pituitary tumour (Cushing's disease)
Dose given every 6 hours for 48 hours
115
Most common cause of Addison's
TB (world)
| Autoimmune (UK)
116
Presentation of Addison's
Postural hypertension
Skin pigmentation
Depression
High K+
Low Na+
117
Investigation for Addison's
Want to see if cortisol production is responding
Short synACTHen test
Normal is cortisol >550nm after 30mins
118
Addison's management
Treat hypotension
Hormone replacement
• Hydrocortisone/fludrocortisone if primary adrenal lesion
119
What is Waterhouse-Friderichsen syndrome?
Adrenal gland failure due to bleeding
Caused by severe (meningococcal) bacterial infection
Septic, low BP, DIC, widespread purpura
120
What is Conn's syndrome and what is it caused by?
Primary aldosteronism - too much aldosterone
Adrenal tumour
121
Signs of Conn's
Uncontrollable hypertension
122
Investigations for Conn's
High Na+
Low K+
Aldosterone:Renin ratio raised
Raised aldosterone has negative feedback on renin
123
Conn's treatment
Aldosterone antagonists / potassium sparing diuretics e.g. spironolactone
124
Causes of phaeochromocytoma
10% are...
MEN syndromes
Bilateral
Malignant
etc.
125
Phaeochromocytoma investigation
24-hour urine collection for catecholamines, (nor)metanephrines, and creatinine
Plasma and serum measurements
126
Phaeochromocytoma management
1. Alpha-blocker e.g. phenoxybenzamine or doxazocin
2. Beta-blocker
3. Hydration
4. Surgical excision of tumour when blood pressure controlled
127
Phenytoin signs of toxicity
Ataxia and nystagmus
128
Patient has just taken a medication, has xanthopsia (seeing yellow), arrhythmias, and heartblock. What is drug is he suffering toxicity to and what is the treatment?
Digoxin for arrhythmias
Treatment: digibind (immune Fab)
129
Lithium toxicity treatment
Renal failure may need haemodialysis
130
When do you need to be cautious of lithium toxicity?
Hyponatraemia - excretion impaired
Decreased renal function
Thiazide diuretics
131
Gentamicin toxicity signs
Tinnitus, deafness, nystagmus, renal failure
132
Theophyline indication and precipitators of toxicity
Indication: COPD and asthma (bronchodilator)
Precipitators: Erythromycin, cimetidine, phenytoin
133
Normal calcium plasma range
2.2 - 2.6 mmol/l
134
Why should we use corrected calcium and how do we calculate it?
50% of calcium bound to albumin, therefore measurement is affected by albumin
total calcium + 0.02(40-albumin)
135
What does PTH do to calcium and how (3)?
Increases serum calcium
* Increases 1a-hydroxylation of 25(OH)D3 (calcifediol) into active vitamin D (calcitriol)
* Mobilises calcium from bone
* Increases renal calcium reabsorption
136
What is the role of calcitriol in calcium metabolism?
Increases calcium (and phosphate) absorption from the gut
Bone remodelling ?acts on both osteoblats and osteoclasts
137
Primary hyperparathyroidism - primary defect and blood test levels
80% parathyroid adenoma
```
PTH - high/normal because of high calcium (inappropriately normal)
Calcium - high
Phosphate - low
Vitamin D - normal
ALP - high/normal
```
138
Secondary hyperparathyroidism - primary defect and blood test levels
CKD
Low vitamin D
Leads to low calcium
Parathyroid hyperplasia
Also caused by vitamin D malabsorption
```
PTH - high
Calcium - low/normal after high PTH
Phosphate - high (not removed in CKD)
Vitamin D - low
ALP - high
```
139
Tertiary hyperparathyroidism - primary defect and blood test levels
Secondary cause treated (e.g. renal transplant), but PTH still autonomously secreted
```
PTH - high
Calcium - high
Phosphate - Low
Vitamin D - norma
ALP - high/normal
```
Similar to primary tests, but PTH is not normal and this progresses from secondary.
140
Causes of hypoparathyroidism and blood test findings
DiGeorge syndrome, post-thyroid surgery
```
PTH - low
Calcium - low
Phosphate - high
Vitamin D - normal
ALP - low/normal
```
141
Bloods in vitamin D deficiency / osteomalacia / rickets
```
Vitamin D - low
Calcium - low (not absorbed)
Phospate - low (not absorbed)
PTH - high (because of low calcium)
ALP - high
```
142
Paget's disease bloods
High ALP
rest normal
143
Osteoporosis bloods
All normal (could have high ALP from a fracture)
144
Risk factors for osteomalacia
```
Anticonvulsants
Phytic acid (food like chapatis) - vit D antagonist
Low sun exposure / vit D intake
```
145
Management of osteoporosis
Reduce smoking and alcohol
Bisphosphonates
Vit D
Weight-bearing exercise
146
Symptoms of hypercalcaemia
```
Stones (renal)
Bones (pain)
Groans (psych)
Moans (abdo pain)
Polyuria
Muscle weakness
```
147
Hypercalcaemia treatment
1. Hydrate
2. Bisphosphonates
3. Correct cause e.g. chemo for cancer
148
What can high calcium, high phosphate, and high ALP suggest in a patient with a cough / dyspnoae and how can this be treated?
Sarcoidosis
Steroids
149
What is a brown tumour and where does it commonly present?
Hyperparathyroidism -> excess osteoclast activity -> bone lesion
Most commonly affects maxilla and mandible
Not a neoplasm
150
How is DEXA Z-score different to T-score?
Age and sex adjusted
151
DEXA T-score in osteoporosis and osteopaenia
Osteoporosis < -2.5
| Osteopaenia -1 to -2.5
152
Causes of hypocalcaemia
Artefact
• Hypoalbuminaemia
High phosphate
• CKD
• Hypoparathyroidism
• Pseudohypoparathyroidism - body doesn't respond
Normal/low phosphate
• Osteomalacia
• Acute pancreatitis
• Overhydration
153
Symptoms of hypocalcaemia
CATs go numb
Carpopedal spasm
Arrhythmia
Tetany (Trousseau's - blood pressure above systolic -> carpal spasm. Chvostek's - tapping inferior cheekbone -> facial spasm)
numb - perioral and acral paraesthesia
154
Mild, CKD and severe hypocalcaemia treatment
Mild - SandoCal
CKD - alfacaldicol
Severe - 10% calcium gluconate IV, then calcium infusion as per trust
155
Are most renal stone patients hyper, normo, or hypocalcaemic?
Normocalcaemic
156
Causes of renal stones
Hyperoxaluria - increased intake, absorption
| Hypercalciuria - increased intake, renal leak
157
Most common constituents of renal stones
1. Calcium - mixed (45%)
2. Calcium oxalate (35%)
3. Triple phosphate "struvite" (10%)
158
Constituents of radiolucent renal stones on x-ray
Uric acid
Cysteine
The rest are radioopaque
159
What are very high serum amylase levels a sign of?
Acute pancreatitis (>10x upper limit)
160
Physiological and pathological causes of raised creatine kinase
Physiological
• Afro-Caribbean
```
Pathological
• Duchenne Muscular Dystophy
• MI
• Rhabdomyolysis
• Statin related myopathy
```
161
How is statin related myopathy treated?
Cessation of statin (reversible)
162
Where is ALP found?
Liver, bone, intestine, placenta
163
Physiological causes of raised ALP
* 3rd trimester of pregnancy
| * Childhood growth spurt
164
Marker of heart failure and why this is
BNP (>400 sensitive for HF, <100 specific for no HF)
Released in response to ventricular stretch
NT-proBNP more sensitive
165
What marker is useful to detect reinfarction of the myocardium?
CK-MB
Rapid decrease so you know if it was recent when high
166
Troponin I/T is a myocardial injury biomarker. When should it be measured? How long does it remain elevated?
6 and 12 hours post onset of chest pain
Remains elevated for 3 - 10 days
167
Patient has HDL deficiency on tests and ABCA1 transporter deficiency. What clinical signs would you expect to see? What is the name of this disease?
Cholesterol ester deposition in organs
• Hepatosplenogemaly
• Enlarged orange/yellow tonsils
Tangier disease
168
What is the least dense lipoprotein?
Chylomicron
169
Role of PCSK9 and anti-PCSK9 mAb
Binding and degradation of LDL receptors
LDL receptors remove LDL from extracellular fluid, but PCSK9 slows this
Anti-PCSK9 mAb stops this, increasing LDLR and decreasing LDL levels
170
Lipoprotein (a) is a risk factor for cardiovascular disease. What can be used to lower this?
Nicotinic acid (niacin)
171
Hyperlipidaemia management
1. Conservative
2. Statins - HMG-CoA reductase inhibitor, reduces intrinsic synthesis of cholesterol in liver
Less often - ezetimibe used (block NPC1L1)
172
Obesity medical management
No meds safely proven for sustained weight loss
Orlistat (gut lipase inhibitor) used. SE - profound flatus and diarrhoea
Rimonabant (cannabinoid antagonist) - trialled and discontinued due to increase risk of suicide
173
Obesity surgical management
Bariatric surgery BMI >40 or >30 with obesity-associated comorbidity
174
'Overweight' BMI
25-30
175
Retinol (vit A) deficiency and excess effects
Deficiency
• Colour blindness
Excess
• Exfoliation
• Hepatitis
176
Cholecalciferol excess effects
Hypercalcaemia
177
```
Anaemia
Neuropathy
Decreased reflexes
Decreased coordination
Effects of which vitamin deficiency?
```
Tocopherol (vit E)
178
Phytomenadione (vit K) defiency effects
Defective clotting
179
What do you test to decide whether vitamin K needs to be given?
Prothrombin time
180
Which vitamins are fat soluble?
A D E K
181
Thiamine (B1) deficiency effects
Beri-beri (wet - oedema, HF. dry - neuro sx)
Neuropathy
Wernicke encephalopathy
182
Test for thiamine deficiency
Erythrocyte transketolase
183
Riboflavin (B2) deficiency effects
Glossitis
| Mucosal damage
184
Test for riboflavin deficiency
Erythrocyte glutathione reductase
185
Pyridoxine (B6) deficiency and excess effects
Deficiency
• Dermatitis
• Anaemia
Excess
• Neuropathy
186
During what therapy should pyridoxine be supplemented?
Isoniazid, as it inhibits metabolic actions of pyridoxine
187
Test for long term pyridoxine status
Erythrocyte AST activation
188
Cobalamin (B12) deficiency effect
Pernicious anaemia
189
Ascorbate (vit C) deficiency and excess effects
Deficiency
| • Scurvy (poor dentition, slow healing wounds, petechiae)
190
Folate (B9) deficiency effects
Megaloblastic anaemia
| Neural tube defect
191
Niacin (B3) deficiency effects
```
Pellagra
• Dementia
• Dermatitis
• Diarrhoea
• Death if untreated
```
192
Iron excess effects, particularly in males
Haemochromatosis
• Deposition of iron in testes
• Hypogonadism
• Decreased libido
Also associated with DM and cirrhosis
193
Iodine deficiency effects
Goitre
| Hypothyroid
194
Zinc deficiency effects
Dermatitis
195
Copper deficiency and excess effects
Deficiency
• Anaemia
Excess
• Wilson's disease
196
Test for high copper in blood
High urine and blood free copper
| Low ceruloplasmin
197
Fluoride deficiency and excess effects
Deficiency
• Dental caries (tooth decay)
Excess
• Fluorosis
198
What vitamin deficiencies are the following conditions associated with:
• Crohns
• Coeliac
• Pancreatic insufficiency
All ADEK, and..
Crohns
• B12 (terminal ileal disease)
• Folate (methotrexate therapy)
• Calcium, phosphate, magnesium, zinc
Coeliac
• Iron
• Thiamine
• Vitamin B6
199
When is the neonatal blood spot screening performed and how does it determine the presence of the following conditions?
• Phenylketonuria
• Congenital hypothyroidism
• Cytstic fibrosis
• Medium chain acylCoA dehydrogenase deficiency
5-9 days
Phenylketonuria
• Phenylalanine levels
Congenital hypothyroidism
• TSH levels
Cystic fibrosis
• Immune reactive trypsin levels
• If positive, DNA mutation detection
MCADD
• Acylcarnitine levels
200
What effect does phenylketonuria have on development?
Intellectual disability, IQ < 50
Severe behaviour problems
Severe epilepsy
201
How can MCADD lead to sudden unexpected infant death?
Hypoglycaemia
202
How many newborns does phenylketonuria occur in?
1 in 10,000
203
What is the PPV of TSH levels in congenital hypothyroidism (Guthrie)?
60-70%
204
How many newborns does CF occur in?
1 in 2500
205
How many newborns does MCADD occur in?
1 in 10,000
206
```
Lens dislocation
Mental retardation
Thromboembolism
Fair skin
Eczema
Brittle hair
These are all features of which condition?
```
Homocystinuria
207
What is specificity?
Probability that someone without the disease correctly tests negative
The percentage of people without the disease that test negative against a total of people that are actually negative
208
What is sensitivity?
Probability that someone with the disease correctly tests positive
The percentage of people with the disease that test positive against a total of people that are actually positive
209
What is positive predictive value?
Probability that someone who tests positive actually has the disease
The percentage of people that have the disease against the number of all people that tested positive (whether they had the disease or not)
210
What is negative predictive value?
Probability that someone who tests negative actually doesn't have the disease
The percentage of people that don't have the disease against all people that tested negative (whether they had the disease or not)
211
What enzyme deficiencies can lead to accumulation of toxins (group 1)?
* Organic acidaemia e.g. Isovaleric acidaemia, Reye's syndrome
* Urea cycle disorders e.g. ornithine transcarbamylase deficiency
* Aminoacidopathies e.g. PKU and maple-syrup urine disease
212
Clinical features of organic acidaemia and treatment
* Metabolic acidosis - ketoacidodic comas, cerebral abnormalities
* Funny smell
* High ammonia
* High anion gap
Treat with low protein diet
213
Reye's syndrome cause and presentation
Aspirin, valproate, anti-emetics
Liver and brain swelling
214
Urea cycle disorder: what is high? what is seen on abg? and treatment
* High ammonia
* Respiratory alkalosis
Treat with low protein diet, sodium benzoate / dialaysis for ammonia removal
215
```
• High phenylalanine
• Blue eyes and fair skin
• Retardation
• Sweaty feet (maple-syrup)
Condition
```
Aminoacidopathy
216
Which metabolic disorders lead to reduced enegy stores (group 2)?
* Glycogen storage disorders e.g. Von Gierke's
* Galactossaemia
* Fatty acid oxidation disorders e.g. MCADD
217
Treatment of glycogen storage disorders
Regular carbohydrates
218
Key features of galactossaemia, testing, and treatment
* Cataracts (high Gal-1 phosphate levels)
* Sepsis
* Hypoglycaemia
* Hepatomegaly
Test with urine reducing agents
Treat with low lactose diet
219
Key features of fatty acid oxidation disorders, testing, and treatment
* Hypoglycaemia
* Low ketones
High blood acylcarnitine
Treat with regular carbohydrates
220
Examples of metabolic disorders that lead to dysmorphic large molecule synthesis (group 3)
* Peroxisomal disorders (can't catabolise long fatty acids or make bile acids)
* Glycosylation disroders
221
Key features of peroxisomal disorders
* Retinopathy
| * Hypotonia
222
Key features and testing of glycosylation disorders
* Retardation
* Nipple inversion
Serum transferrin
223
Give an example of a lysosomal metabolic disorder leads to defects in large molecule metabolism (group 4) and lipid accumulation in neurones
Tay Sachs disease
224
Testing of lysosomal disorders
Urine mucooligopolysaccharide and WBC enzyme levels
225
Examples of mitochondrial (group 5) disorders
MELAS
Kearn's Sayre
Barth syndrome
226
Key features and testing of mitochondrial disorders
MELAS - the name: mitochondrial encephalopathy, lactic acidosis, stroke-like epidoses
Kearn's Sayre - retinopathy, deafness, ataxia
Barth - cardiomyopathy, neutropaenia
High lactate and CK after fasting
Muscle biopsy diagnostic
227
Diagnosis of diabetes mellitus
```
2 of, or typical symptoms + 1 of:
• Fasting glucose > 7
• Random glucose > 11.1
• OGTT > 11.1
• HbA1C > 48 (NICE recommendation)
```
228
What does random/OGTT of > 7.8 or < 11.1 mean?
Impaired glucose tolerance
229
What does fastin glucose > 6.1 but < 7.0 mean?
Impaired fasting glucose
230
Hyperosmolar hyperglycaemic state (HHS) criteria
pH > 7.3
Osmolarity >320
Blood glucose > 30
231
How do HHS patients present?
Confusion and clinical dehydration
| Develops over few days
232
HHS management
Fluid replacement
Potassium supplement
Insulin
233
DKA management
VBG (or ABG in resp function concerns
Fluids (add KCl if potassium low), front load replacement, maintence/taper off
Insulin
234
When is DKA resolved?
Ketones < 0.6
| pH > 7.3
235
What causes hypoinsulinaemic hypoglycaemia?
```
+ve ketones
• alcohol binge, no food
• pituitary insufficiency
• Addison's
• liver failure
• strenuous exercise
• premature neonate
```
-ve ketones
• non-pancreatic neoplasms (fibrosarcomata, fibromata)
• metabolic disorder in neonate
236
By what age do you have a functional maturity of glomerular filtration rate
2 years
237
Why do children have less kidney reaborption and concentrating ability than adults?
Reabsorption - short proximal tubule
Concentration - short loops of Henle and collecting duct
238
Why do children have persistant kidney sodium loss?
Relatively aldosterone-insensitive distal tubule
239
How is water lost in children a lot more than it is as an adult?
Transepidermal
• Increased skin blood flow
• High surface area to body weight ratio
• High metabolic/resp rate
240
How can bones be affected in premature babies?
Osteopaenia of prematurity
• Not enough calcium and phosphate
(high ALP)
241
When can hypernatraemia be common in babies?
First 2 weeks of life
242
What can cause hyponatraemia in neonates?
First 4-5 days
• Excess water intake
• SIADH secondary to infection or intraventricular haemorrhage
After first 4-5 days
• Immature tubular function in patients on diuresis (sodium loss)
Hyperglycaemia (normal but appears low)
Congenital adrenal hyperplasia
243
How does congenital adrenal hyperplasia present?
21-hydroxylase deficiency
Low cortisol and aldosterone
High 17-hydroxyprogesterone
High androgens
Ambiguous genitalia in females
Salt wasting crisis in males
Growth acceleration
244
Neonatal jaundice bilirubin threshold for phototherapy and exchange for term and premature babies
Term
• Photo - 350
• Exchange - 450
Premature
• Photo - 120
• Exchange - 230
245
Gold standard measure of GFR
Inulin (difficult to test so research only)
246
Better marker than creatinine for renal function
cystatin C - produced by all nucleated cells
247
What is the problem of the MDRD equation in estimating the GFR with creatinine?
May underestimate GFR if young + above average weight
248
First line investigation for upper UTI obstruction e.g. kidney stones
CT KUB
249
Which investigation is good at looking at anatomical defects of the urinary system and how it is working in children?
IV urogram
250
AKI definition
Rise in creatinine > 26.5 or 1.5x (3x if severe) baseline, in 48 hours
or
Urine output < 0.5mls/kg/hr but bladder and prostate pathology may cause this too
251
Causes of pre-renal AKI
```
NSAIDs
ACEi
Diuretics
Hypotension
Shock
Sepsis
```
252
Indications for dialysis as an emergency
```
AEIOU
• Acidosis (metabolic)
• Electrolyte disturbance
• Intoxication e.g. lithium, aspirin
• Overload
• Uraemic encephalopathy
```
253
Does urea or creatinine increase more in AKI and CKD?
AKI - urea
| CKD - creatinine
254
GFR in stage 1-5 CKD (kidney damage with normal GFR, mild, moderate, severe, end-stage)
1. >90
2. >60
3. >30
4. >15
5. <15
255
2 causes of CKD
Diabetes (common to see high K+ in CKD)
| Hypertension
256
Is AKI and CKD reversible
AKI is reversible, CKD isn't
257
Treatment of acidosis in CKD
oral sodium bicarbonate
258
Most important complication of CKD that leads to death
Uraemic cardiomyopathy - LV hypertrophy, calcified plaques
259
Homeostatic function effects of CKD
acidosis, hyperkalaemia
260
Hormonal effects of CKD
anaemia (loss of EPO)
| renal bone disease (low vit D)
261
How can haemodialysis be done and how often?
Tunneled central line (Tessio line) or arteriovenous fistulae
3x a week
262
Pertinoeal dialysis deliver medium
Tenckoff catheter
263
Incision and location for kidney transplant
Rutherford Morrison incision (hockey stick scar)
| Right iliac fossa
