Chem Path Flashcards
(127 cards)
1
Q
How is osmolarity calculated?
A
2(Na + K) + urea + glucose
2
Q
Osmolality and osmolarity
A
Should be roughly the same
Any difference = osmolar gap
Physiological determinants = Na, K, Cl, HCO3, urea glucose
Pathological determinants = endogenous glucose, exogenous ethanol, mannitol
3
Q
Serum osmolality normal range
A
275 - 295 mmol/kg
4
Q
Na
135 - 145
A
Extra cellular cation
Extra cellular fluid volume depends on Na concentration
5
Q
Hyponatraemia
A
Treat underlying cause only
death
6
Q
Correcting a hyponatraemia
A
Only incr Na by 1mmol/l/hr
Rapid correction -> central pontine myelinolysis=
Pseudo bulbar palsy, locked in syndrome, paraparesis
7
Q
Hyponatraemia + normal osmolality
A
Pseudohyponatraemia
A spurious sample E.g. From drip arm
Hyperlipidaemia
Hyperproteinaemia
8
Q
Hyponatraemia + high osmolality ( >295 )
A
Due to glucose or mannitol
9
Q
Hyponatraemia + low osmolality (
A
True hyponatraemia
Differentiate between causes using either volume status or renal involvement
10
Q
Hypovolaemic hyponatraemia
A
Urine Na:
> 20 = diuretics, Addison’s - salt losing nephropathy
11
Q
Euvolaemic hyponatraemia
A
Urine Na:
> 20 = SIADH, primary polydipsia, severe hypothyroidism
12
Q
Hypervolaemic hyponatraemia
A
Urine Na:
> 20 = acute / chronic renal failure
13
Q
SIADH
A
Euvolaemic hyponatraemia
Excess ADH -> Urine osm >100 (> plasma osm), urine Na > 20
Normal renal, adrenal, thyroid + cardiac function - dx of exclusion
Causes:
Malig= small cell, pancreas, prostate, lymphoma
CNS= meningoencephalitis, haemorrhage, abscess
Pulm= TB, pneumonia, abscess
Drugs= opiates, SSRIs, carbamazepine
14
Q
Addison’s disease
A
Aka primary adrenal insufficiency
Reduced aldosterone + cortisol
Increase ACTH
Hyponatraemia + hyperkalaemia + hypoglycaemia
Hyperpigmentation, postural hypotension, weight loss
15
Q
Chronic kidney disease
A
Urinary protein loss -> oedema
Reduced circulating vol -> RAS activation -> incr [Na] -> ADH
= hypervolaemic hypernatraemia
+ hyperkalaemia + azotaemia - high urea + creatinine
16
Q
Hypernatraemia
>145
A
Clinically significant = >148
Often iatrogenic
Sx= thirst -> confusion -> seizures + ataxia -> coma
17
Q
Hypovolaemia hypernatraemia: causes
A
Vom/diarrhoea Sweating Burns Loop diuretics Osmotic diuresis Renal failure
18
Q
Euvolaemic hypernatraemia: causes
A
Tachypnoea
Sweating
Diabetes insipidous
No water
19
Q
Hypervolaemic hypernatraemia: causes
A
Mineralocorticoid excess e.g. Conn’s
Hypertonic saline
20
Q
Diabetes insipidus
A
Euvolaemic hypernatraemia Polyuria + polydipsia Urine:plasma osm 600 = normal Concentrates 400-600 = primary polydipsia Concentrates with DDAVP = cranial DI Doesn't concentrate = nephrogenic DI
21
Q
Causes of cranial DI
A
Head trauma
Tumour
Surgery
22
Q
Causes of nephrogenic DI
A
I.e. ADH insensitivity
Inherited
CRF
Drugs: lithium, demeclocycline
23
Q
Conn’s syndrome
A
Aldosterone secreting tumour
= resistant htn, hypoK, metabolic acidosis with hyperNa rarely
24
Q
Potassium
3.5 - 5.5
A
Intracellular cation
25
Causes of hypokalaemia
Depletion: GI loss, hyperaldosteronism, osmotic diuresis
Shift to intracellular fluid: insulin, beta agonists, alkalosis
Rare: renal tubular acidosis, hypomagnesaemia
26
Causes of hyperkalaemia
Excessive intake: oral, parenteral, stored blood transfusion
Shift to extra-cellular fluid: acidosis, insulin shortage, tissue damage
Reduced excretion: ARF-oliguria phase, CRF-late, K sparing diuretics, Addisons, NSAIDs, ACEi
27
What are the ECG changes in hyperkalaemia and how is it managed?
Tall tented T waves, small P waves, wide QRS complex
Risk -> v fib
Give 10ml 10% calcium gluconate to increase the threshold potential and stabilise the myocardium
28
How do you calculate the anion gap?
(Na + K) - Cl - HCO3
29
What is the normal anion gap range?
14 - 18
30
What are causes of an increased anion gap?
Ketoacidosis
Uraemia
Lactic acidosis
Toxins: ethylene glycol, methanol, paraldehyde, salicylates
31
Which LFTs are raised in a hepatic picture?
ALT more liver specific than AST
Alcoholic liver disease: AST:ALT = 2:1
Viral liver disease: AST:ALT
32
Which LFTs are raised in an obstructive picture?
ALP
| GGT
33
When is increased ALP seen?
```
Cholestasis
Bone disease
Pregnancy
PBC
Prostate cancer
```
34
When is increased GGT seen?
Chronic + acute alcohol use
Bile duct disease
Metastasis
35
Acute intermittent porphyria
AD Porphobilinogen deaminase deficiency
Abdo pain, N+V, seizures, psych disturbance, htn, tachycardia
In acute attack give haem arginate
+ ALA + PBG in urine
Port wine urine
Attacks triggered by ALA synthase inducers: steroids, ethanol, barbituates, stress
36
What drugs are contraindicated in porphyria?
Diclofenac
| Co trimoxazole
37
What can cause neuro damage in porphyria?
5 aminolavulinic acid
38
Which acute porphyrias have skin lesions?
HCP: hereditary coproporphyria
Neuro visceral + skin lesions
Raised porphyrins in faeces/ urine
VP: variegate porphyria
39
Which porphyria shave skin lesions only?
Non-acute ones:
PCT: Porphyria cutanea tarda
Uroporphyrinogen decarboxylase deficiency
EPP: erythropoietic protoporphyria
Photosensitive, burning, itching, oedema
CEP: congenital erythropoietic porphyria
40
Hypothyroidism
Incr TSH, decr T4
Primary atrophic: diffuse lymphocytic infiltrate, no goitre
Hashimoto's: plasma cell infiltrate + goitre, elderly, female, autoAbs, Askanazy
Iodine deficiency
Post surgery/radio iodine / drugs: lithium, amiodarone
41
High uptake hyperthyroidism
Graves: autoantibodies, women>men
Toxic multinodular goitre:
Toxic adenoma: 'hot nodule'
42
Low uptake hyperthyroidism
DeQuervains: self limiting, post viral, painful goitre
Aka giant cell thyroiditis
Post partum thyroiditis
43
Treatment of hyperthyroidism
Beta blockers + carbimazole
| Radio iodine / surgery
44
Treatment of hypothyroidism
Thyroxine
45
Papillary thyroid cancer
>60%
30-40yrs
Req surgery +- radio iodine
Then thyroxine replacement
46
Follicular thyroid cancer
```
25%
Well differentiated
Spreads early
Surgery +- radio iodine
Thyroxine replacement
```
47
Medullary thyroid cancer
5%
MEN 2 para follicular cells
Calcitonin
48
Thyroid MALT lymphoma
RF= chronic Hashimoto's
| Good prognosis
49
Anaplastic thyroid cancer
Rare
Elderly
Poor response
50
Cushing's disease
Most common cause of Cushing's syndrome
Pituitary tumour
Cushingoid features
High dose dexamethasone test suppresses cortisol
51
Causes of Cushing's syndrome
```
85% Cushing's disease
10% adrenal tumour- zona fasiculata
5% ectopic ACTH
Iatrogenic steroid use - fails to suppress cortisol using high dose dexamethasone test
Treat underlying cause
```
52
Causes of Addison's
AI
TB- commonest worldwide
Adrenal haemorrhage
Amyloidosis
53
Presentation of Addisons
HypoNa + HyperK + Hypo glycaemia
Pigmentation, lethargy, depression
Ix: synACTHen test
Rx: hormone replacement hydrocortisone/ fludrocortisone if primary adrenal
54
Conn's
Adrenal tumour zona glomerulosa -> uncontrollable htn
HyperNa + HypoK
Ix: aldosterone:renin ratio
Rx: aldosterone antagonists= spironolactone, amiloride
55
Phaeochromocytoma
Adrenal medulla tumour = adrenaline
Ix: plasma + 24 hr urine metadrenaline measurement/ catecholamines VMA
Rx: alpha blockade, beta blockade, bp controlled -> surgery
56
HypoCa
Decr phosphate
Incr PTH
Decr vit D
Osteomalacia/ Rickets
57
HypoCa
Incr phosphate
Incr PTH
Secondary hyperparathyroidism
58
HypoCa
Incr phosphate
Decr PTH
Hypoparathyroidism
```
Primary= Di George
Secondary= post thyroid surgery
```
59
HyperCa
Decr phosphate
Incr PTH
Primary hyperparathyroidism
Tertiary hyperparathyroidism
60
Incr ALP only
Paget's
Bone remodelling
Bone pain
61
HyperCa
Incr albumin
Incr urea
Dehydration
62
HyperCa
Normal ALP
Myeloma
Excess vit D
Sarcoid
63
Hypercalcaemia
```
Renal Stones
Bone pains
Psychic Moans
Abdominal Groans
Polyuria
Muscle weakness
```
64
Hypocalcaemia
```
Peri oral paraesthesia
Carpopedal spasm
Trousseau
Neuro-Musc excitability
Chvostek
```
65
Renal stones
Radio opaque:
Mixed 45%, oxalate 35%, phosphate 1%
Triple phosphate aka struvite 10%
Radio lucent:
Uric acid 5%, Cysteine 1-2%
66
Incr amylase
Acute pancreatitis
| Mumps
67
Incr creatine kinase
Duchenne
Rhabdomyolysis
Statin related myopathy
MI : CK MB
68
Troponin
Not enzyme - marker
I: 6hrs post onset chest pain
T: 12hrs post onset
Remain elevated 3-10 days
69
Diagnostic criteria for MI
Typical Troponin or CK MB
+ one of:
Ischaemic sx, q waves, ischaemic ECG, coronary artery interv
70
Phenytoin
Ataxia + nystagmus
Once liver saturated -> surge in serum concentration
Omit or reduce dose in toxicity
71
Digoxin
```
Coarse tremor, lethargy, fits, arrhythmia
Yellow/blurred vision
Anorexia, nausea + vom, confusion
With diuretics/RF -> impaired excretion
Haemodialysis may be required if RF
Under treatment and toxicity sx similar
```
72
Gentamycin
Tinnitus, deafness, nystagmus, RF
Use single daily dosing monitoring peak + trough levels
Omit or reduce dose in toxicity
73
Theophylline
Arrhythmia, anxiety, tremor, nystagmus
Concentration increased with concurrent erythromycin, cimetidine, phenytoin
Reduced half life in smokers, incr half life in liver disease
Acute asthma -> cardiac arrest
74
Lipid soluble drug metabolism in the liver
1. Oxidation by cytochrome p450
| 2. Conjugation by sulphate/gluconaride?
75
Lithium
If taken with thiazides diuretics incr risk toxicity
| Decr excretion -> incr plasma concentration
76
Unfractionated heparin
Requires regular APTT monitoring
77
Cocaine
Aggressive, paranoid
Tachycardia
Sudden death
78
Ecstasy
```
Feverish, confused, sweaty
Hyperthermia
Dilated pupils
Raised urea + creatinine
High myoglobin
```
79
Heroin
Depressed breathing
Collapse
6 MAM
80
Atenolol OD
IV atropine
| Glucagon
81
Carbon monoxide poisoning
```
Headache
Nausea + dizziness
Collapse
CarboxyHb
O2
Hyperbaric O2
```
82
Paraquat consumption?
Activated charcoal
83
Salicylate toxicity
Hyperventilation
Sweaty, nauseous
Ringing in ears
Mixed acid-base disturbance
84
TCA toxicity
```
Drowsy
Tachycardic
Dilated pupils
Wide QRS interval
Hyperreflexia
```
85
Organophosphate toxicity
```
Farmer
Nausea + vom
Headache, hypersalivation
SOB
Sweaty, flaccid paresis
```
86
Testing for drugs
Immunoassays can test for all classes of drugs of abuse
Blood sample req for gas chromatog. mass spectroscopy
Paracetamol - colorimetric test
Benzos + antipsychotics - liquid chromatography
Thin layer chromatography to analyse stool, urine + liver samples
Saliva- can test for all except THC
87
Types of primary hypercholesteraemia
Familial T2: apoB, PCSK9, AD-LDLR, AR-LDLRAP1
Polygenic hypercholesteraemia
Familial hyper-alpha-lipoproteinaemia
Phytosterolaemia: ABC, G5 + G8
88
Types of primary triglyceridaemia
Familial T1: lipoproteinlipase/apoC II deficiency
Familial T4: incr TG synth
Familial T5: apoA V deficiency
89
Types of mixed hyperlipidaemia
Familial combined hyperlipidaemia
Familial dys-beta- lipidproteinaemia
Familial hepatic lipase deficiency
90
Hypolipidaemia
A-beta-lipoproteinaemia: MTO deficiency
Tangier disease: HDL deficiency
Hypo-alpha- lipoproteinaemia: apoA1 mutations
Hypo-beta- lipoproteinaemia : truncated apo-beta-protein
91
Lipoproteins in order of density
Chylomicron
92
PCSK9
Binds LDLR + promotes degradation
Loss of function mutation -> low LDL levels
A novel LDL lowering Rx: anti PCSK9 mab
93
Lipoprotein a
CVD risk factor
| Rx: nicotinic acid
94
Vit A
| Aka retinol
Def= night blindness
Exc= exfoliation, hepatitis
High levels teratogenic
95
Vit D
| Aka cholecalciferol
```
Def= osteomalacia
Exc= hypercalcaemia
```
96
Vit E
| Aka tocopherol
Def= anaemia, neuropathy, IHD
97
Vit K
| Aka phytomenadione
Def= defective clotting
| Measured with PTT
98
Vit B1
| Thiamine
Def= Beri Beri, neuropathy, Wernicke's
| Measured using RBC transketolase
99
Vit B2
| Aka riboflavin
Def= glossitis
| Measured using RBC glutathione reductase
100
Vit B6
| Aka pyridoxine
Def= dermatitis, anaemia
Exc= neuropathy
Measured using: RBC AST activation
101
Vit B12
| Aka cobalamin
Def= pernicious anaemia
102
Vit B3
| Aka niacin
Def= pellagra: Dementia, Dermatitis, Diarrhoea
| Casal's necklace
103
Vit C
| Aka ascorbate
Def= scurvy
Exc= renal stones
Measure using plasma
104
Folate
| Aka folic acid
```
Def= megaloblastic anaemia
Exc= haemochromatosis
```
105
Iodine
Def= hypothyroidism + goitre
106
Zinc
Def= dermatitis
107
Fluoride
```
Def= dental caries
Exc= fluorosis
```
108
Phenylketonuria
```
Phenylalanine hydroxylase deficiency
Ix: Guthrie aka neonatal blood spot
Fair hair, dev delay 6-12 months, severely impaired IQ
Eczema, seizures, musty smell
Rx: low protein diet, avoid aspartame!
```
109
MCAAD
Fatty acid oxidation disorder
| Test acyl carnitine levels by tandem mass spectrometry
110
Mitochondrial disorders
| Aka defective ATP production
Barth: at birth cardiomyopathy, neutropaenia, myopathy
MELAS: 5-15yrs lactic acidosis, mitochondrial encephalopathy, stroke like episodes
Kearns Sayre: 12-30yrs retinopathy, deafness, ataxia
111
Homocysteinuria
Cystathionine synthetase deficiency
Fair skin, brittle hair, dev delay
Convulsions, skeletal abnormalities, thrombosis
Rx: vit B6 pyridoxine/ low methionine diet
112
Von Gierke's
Glucose-6-phosphate deficiency
Glycogen storage disorder
Hypoglycaemia, hepatomegaly, renal enlargement
113
Maple syrup urine disease
Organic aciduria=
impaired metabolism of leucine, isoleucine, valine
Toxic encephalopathy: lethargy, poor feeding, hypotonia, seizures
Sweet odour, sweaty feet
Ix: gas chromatography
114
Fabry's disease
```
Lysosomal storage disorder
Alpha- galactosidase deficiency
Dev delay, dysmorphia, seizures
Deafness, blindness, hepatosplenomegaly
Cherry red spot
```
115
Galactosaemia
Galactose-1-phosphate uridyltransferase 9p13
Cataracts, poor feeding, lethargy, conjugated hyper BR
Reducing sugars in urine, +ve Fehlings +ve Benedicts
-ve glucose oxidase strip test
116
Other glycogen storage disorders
Pompe's: lysosomal-alpha-glucosidase
Cori's: amylo-1-6-glucosidase
McArdles: phosphorylase
All-> liver + muscle dysfunction
117
Impaired glucose tolerance
Random glucose > 7.8 but
118
DM
Sx + 2 of:
Fasting glucose >7
Random glucose >11.1
Oral glucose tolerance test > 11.1
(HbA1c>48)
119
Impaired fasting glucose
Fasting glucose > 6.1 but
120
Hyperinsulinaemic hypoglycaemia causes
Iatrogenic insulin
Insulinoma
Sulphonyl urea excess
121
Hypoinsulinaemic hypoglycaemia causes
+ve ketones: alcohol, fasting, Addisons, liver failure, pituitary insufficiency
-ve ketones: non-pancreatic neoplasms: fibromata/sarcomata
122
Normal GFR
120ml/hr
Gold standard = inulin
In reality creatinine clearance used to estimate GFR:
Cockcroft Gault + MDRD
According to Karim, to calculate:
Urine [creatinine] x (vol) / plasma [creatinine] FFS seriously
123
Causes of AKI
Pre renal: decr perfusion, no structural abnormality
Renal: vascular, glomerular, tubular, interstitial
Post renal: obstruction
124
CKD
1. Kidney damage + normal GFR >90ml/min
2. Mild = 60-89 ml/min
3. Mod = 30-59 ml/min
4. Sev = 15-29 ml/min
5. End stage =
125
Causes + consequences of CKD
Common causes: DM, htn, atherosclerosis, chronic GN, PKD
Consequences:
Homeostatic failure= acidosis + hyperkalaemia
Hormonal failure = anaemia, renal osteodystrophy
CVD= cardiovascular calcification, uraemic cardiomyopathy
Uraemia + death
126
```
HypoCa
Incr phosphate
Incr PTH
Rounded facies
Short metacarpals
```
Looks like secondary hyperparathyroidism BUT extra clues!
Pseudo hypothyroidism
Due to PTH resistance, it's increased but the kidneys and bones aren't responding appropriately!
127
Skeletal defects despite normal bone profile
Pseudopseudohypoparathyroidism
| Inherited
