Chem Path Flashcards
How is osmolarity calculated?
2(Na + K) + urea + glucose
Osmolality and osmolarity
Should be roughly the same
Any difference = osmolar gap
Physiological determinants = Na, K, Cl, HCO3, urea glucose
Pathological determinants = endogenous glucose, exogenous ethanol, mannitol
Serum osmolality normal range
275 - 295 mmol/kg
Na
135 - 145
Extra cellular cation
Extra cellular fluid volume depends on Na concentration
Hyponatraemia
Treat underlying cause only
death
Correcting a hyponatraemia
Only incr Na by 1mmol/l/hr
Rapid correction -> central pontine myelinolysis=
Pseudo bulbar palsy, locked in syndrome, paraparesis
Hyponatraemia + normal osmolality
Pseudohyponatraemia
A spurious sample E.g. From drip arm
Hyperlipidaemia
Hyperproteinaemia
Hyponatraemia + high osmolality ( >295 )
Due to glucose or mannitol
Hyponatraemia + low osmolality (
True hyponatraemia
Differentiate between causes using either volume status or renal involvement
Hypovolaemic hyponatraemia
Urine Na:
> 20 = diuretics, Addison’s - salt losing nephropathy
Euvolaemic hyponatraemia
Urine Na:
> 20 = SIADH, primary polydipsia, severe hypothyroidism
Hypervolaemic hyponatraemia
Urine Na:
> 20 = acute / chronic renal failure
SIADH
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
Addison’s disease
Aka primary adrenal insufficiency
Reduced aldosterone + cortisol
Increase ACTH
Hyponatraemia + hyperkalaemia + hypoglycaemia
Hyperpigmentation, postural hypotension, weight loss
Chronic kidney disease
Urinary protein loss -> oedema
Reduced circulating vol -> RAS activation -> incr [Na] -> ADH
= hypervolaemic hypernatraemia
+ hyperkalaemia + azotaemia - high urea + creatinine
Hypernatraemia
>145
Clinically significant = >148
Often iatrogenic
Sx= thirst -> confusion -> seizures + ataxia -> coma
Hypovolaemia hypernatraemia: causes
Vom/diarrhoea Sweating Burns Loop diuretics Osmotic diuresis Renal failure
Euvolaemic hypernatraemia: causes
Tachypnoea
Sweating
Diabetes insipidous
No water
Hypervolaemic hypernatraemia: causes
Mineralocorticoid excess e.g. Conn’s
Hypertonic saline
Diabetes insipidus
Euvolaemic hypernatraemia Polyuria + polydipsia Urine:plasma osm 600 = normal Concentrates 400-600 = primary polydipsia Concentrates with DDAVP = cranial DI Doesn't concentrate = nephrogenic DI
Causes of cranial DI
Head trauma
Tumour
Surgery
Causes of nephrogenic DI
I.e. ADH insensitivity
Inherited
CRF
Drugs: lithium, demeclocycline
Conn’s syndrome
Aldosterone secreting tumour
= resistant htn, hypoK, metabolic acidosis with hyperNa rarely
Potassium
3.5 - 5.5
Intracellular cation
Causes of hypokalaemia
Depletion: GI loss, hyperaldosteronism, osmotic diuresis
Shift to intracellular fluid: insulin, beta agonists, alkalosis
Rare: renal tubular acidosis, hypomagnesaemia
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
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
How do you calculate the anion gap?
(Na + K) - Cl - HCO3
What is the normal anion gap range?
14 - 18
What are causes of an increased anion gap?
Ketoacidosis
Uraemia
Lactic acidosis
Toxins: ethylene glycol, methanol, paraldehyde, salicylates
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
Which LFTs are raised in an obstructive picture?
ALP
GGT
When is increased ALP seen?
Cholestasis Bone disease Pregnancy PBC Prostate cancer
When is increased GGT seen?
Chronic + acute alcohol use
Bile duct disease
Metastasis
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
What drugs are contraindicated in porphyria?
Diclofenac
Co trimoxazole
What can cause neuro damage in porphyria?
5 aminolavulinic acid
Which acute porphyrias have skin lesions?
HCP: hereditary coproporphyria
Neuro visceral + skin lesions
Raised porphyrins in faeces/ urine
VP: variegate porphyria
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
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
High uptake hyperthyroidism
Graves: autoantibodies, women>men
Toxic multinodular goitre:
Toxic adenoma: ‘hot nodule’
Low uptake hyperthyroidism
DeQuervains: self limiting, post viral, painful goitre
Aka giant cell thyroiditis
Post partum thyroiditis
Treatment of hyperthyroidism
Beta blockers + carbimazole
Radio iodine / surgery
Treatment of hypothyroidism
Thyroxine
Papillary thyroid cancer
> 60%
30-40yrs
Req surgery +- radio iodine
Then thyroxine replacement
Follicular thyroid cancer
25% Well differentiated Spreads early Surgery +- radio iodine Thyroxine replacement
Medullary thyroid cancer
5%
MEN 2 para follicular cells
Calcitonin
Thyroid MALT lymphoma
RF= chronic Hashimoto’s
Good prognosis
Anaplastic thyroid cancer
Rare
Elderly
Poor response
Cushing’s disease
Most common cause of Cushing’s syndrome
Pituitary tumour
Cushingoid features
High dose dexamethasone test suppresses cortisol
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
Causes of Addison’s
AI
TB- commonest worldwide
Adrenal haemorrhage
Amyloidosis
Presentation of Addisons
HypoNa + HyperK + Hypo glycaemia
Pigmentation, lethargy, depression
Ix: synACTHen test
Rx: hormone replacement hydrocortisone/ fludrocortisone if primary adrenal
Conn’s
Adrenal tumour zona glomerulosa -> uncontrollable htn
HyperNa + HypoK
Ix: aldosterone:renin ratio
Rx: aldosterone antagonists= spironolactone, amiloride
Phaeochromocytoma
Adrenal medulla tumour = adrenaline
Ix: plasma + 24 hr urine metadrenaline measurement/ catecholamines VMA
Rx: alpha blockade, beta blockade, bp controlled -> surgery
HypoCa
Decr phosphate
Incr PTH
Decr vit D
Osteomalacia/ Rickets
HypoCa
Incr phosphate
Incr PTH
Secondary hyperparathyroidism
HypoCa
Incr phosphate
Decr PTH
Hypoparathyroidism
Primary= Di George Secondary= post thyroid surgery
HyperCa
Decr phosphate
Incr PTH
Primary hyperparathyroidism
Tertiary hyperparathyroidism
Incr ALP only
Paget’s
Bone remodelling
Bone pain
HyperCa
Incr albumin
Incr urea
Dehydration
HyperCa
Normal ALP
Myeloma
Excess vit D
Sarcoid
Hypercalcaemia
Renal Stones Bone pains Psychic Moans Abdominal Groans Polyuria Muscle weakness
Hypocalcaemia
Peri oral paraesthesia Carpopedal spasm Trousseau Neuro-Musc excitability Chvostek
Renal stones
Radio opaque:
Mixed 45%, oxalate 35%, phosphate 1%
Triple phosphate aka struvite 10%
Radio lucent:
Uric acid 5%, Cysteine 1-2%
Incr amylase
Acute pancreatitis
Mumps
Incr creatine kinase
Duchenne
Rhabdomyolysis
Statin related myopathy
MI : CK MB
Troponin
Not enzyme - marker
I: 6hrs post onset chest pain
T: 12hrs post onset
Remain elevated 3-10 days
Diagnostic criteria for MI
Typical Troponin or CK MB
+ one of:
Ischaemic sx, q waves, ischaemic ECG, coronary artery interv
Phenytoin
Ataxia + nystagmus
Once liver saturated -> surge in serum concentration
Omit or reduce dose in toxicity
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
Gentamycin
Tinnitus, deafness, nystagmus, RF
Use single daily dosing monitoring peak + trough levels
Omit or reduce dose in toxicity
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
Lipid soluble drug metabolism in the liver
- Oxidation by cytochrome p450
2. Conjugation by sulphate/gluconaride?
Lithium
If taken with thiazides diuretics incr risk toxicity
Decr excretion -> incr plasma concentration
Unfractionated heparin
Requires regular APTT monitoring
Cocaine
Aggressive, paranoid
Tachycardia
Sudden death
Ecstasy
Feverish, confused, sweaty Hyperthermia Dilated pupils Raised urea + creatinine High myoglobin
Heroin
Depressed breathing
Collapse
6 MAM
Atenolol OD
IV atropine
Glucagon
Carbon monoxide poisoning
Headache Nausea + dizziness Collapse CarboxyHb O2 Hyperbaric O2
Paraquat consumption?
Activated charcoal
Salicylate toxicity
Hyperventilation
Sweaty, nauseous
Ringing in ears
Mixed acid-base disturbance
TCA toxicity
Drowsy Tachycardic Dilated pupils Wide QRS interval Hyperreflexia
Organophosphate toxicity
Farmer Nausea + vom Headache, hypersalivation SOB Sweaty, flaccid paresis
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
Types of primary hypercholesteraemia
Familial T2: apoB, PCSK9, AD-LDLR, AR-LDLRAP1
Polygenic hypercholesteraemia
Familial hyper-alpha-lipoproteinaemia
Phytosterolaemia: ABC, G5 + G8
Types of primary triglyceridaemia
Familial T1: lipoproteinlipase/apoC II deficiency
Familial T4: incr TG synth
Familial T5: apoA V deficiency
Types of mixed hyperlipidaemia
Familial combined hyperlipidaemia
Familial dys-beta- lipidproteinaemia
Familial hepatic lipase deficiency
Hypolipidaemia
A-beta-lipoproteinaemia: MTO deficiency
Tangier disease: HDL deficiency
Hypo-alpha- lipoproteinaemia: apoA1 mutations
Hypo-beta- lipoproteinaemia : truncated apo-beta-protein
Lipoproteins in order of density
Chylomicron
PCSK9
Binds LDLR + promotes degradation
Loss of function mutation -> low LDL levels
A novel LDL lowering Rx: anti PCSK9 mab
Lipoprotein a
CVD risk factor
Rx: nicotinic acid
Vit A
Aka retinol
Def= night blindness
Exc= exfoliation, hepatitis
High levels teratogenic
Vit D
Aka cholecalciferol
Def= osteomalacia Exc= hypercalcaemia
Vit E
Aka tocopherol
Def= anaemia, neuropathy, IHD
Vit K
Aka phytomenadione
Def= defective clotting
Measured with PTT
Vit B1
Thiamine
Def= Beri Beri, neuropathy, Wernicke’s
Measured using RBC transketolase
Vit B2
Aka riboflavin
Def= glossitis
Measured using RBC glutathione reductase
Vit B6
Aka pyridoxine
Def= dermatitis, anaemia
Exc= neuropathy
Measured using: RBC AST activation
Vit B12
Aka cobalamin
Def= pernicious anaemia
Vit B3
Aka niacin
Def= pellagra: Dementia, Dermatitis, Diarrhoea
Casal’s necklace
Vit C
Aka ascorbate
Def= scurvy
Exc= renal stones
Measure using plasma
Folate
Aka folic acid
Def= megaloblastic anaemia Exc= haemochromatosis
Iodine
Def= hypothyroidism + goitre
Zinc
Def= dermatitis
Fluoride
Def= dental caries Exc= fluorosis
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!
MCAAD
Fatty acid oxidation disorder
Test acyl carnitine levels by tandem mass spectrometry
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
Homocysteinuria
Cystathionine synthetase deficiency
Fair skin, brittle hair, dev delay
Convulsions, skeletal abnormalities, thrombosis
Rx: vit B6 pyridoxine/ low methionine diet
Von Gierke’s
Glucose-6-phosphate deficiency
Glycogen storage disorder
Hypoglycaemia, hepatomegaly, renal enlargement
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
Fabry’s disease
Lysosomal storage disorder Alpha- galactosidase deficiency Dev delay, dysmorphia, seizures Deafness, blindness, hepatosplenomegaly Cherry red spot
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
Other glycogen storage disorders
Pompe’s: lysosomal-alpha-glucosidase
Cori’s: amylo-1-6-glucosidase
McArdles: phosphorylase
All-> liver + muscle dysfunction
Impaired glucose tolerance
Random glucose > 7.8 but
DM
Sx + 2 of:
Fasting glucose >7
Random glucose >11.1
Oral glucose tolerance test > 11.1
(HbA1c>48)
Impaired fasting glucose
Fasting glucose > 6.1 but
Hyperinsulinaemic hypoglycaemia causes
Iatrogenic insulin
Insulinoma
Sulphonyl urea excess
Hypoinsulinaemic hypoglycaemia causes
+ve ketones: alcohol, fasting, Addisons, liver failure, pituitary insufficiency
-ve ketones: non-pancreatic neoplasms: fibromata/sarcomata
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
Causes of AKI
Pre renal: decr perfusion, no structural abnormality
Renal: vascular, glomerular, tubular, interstitial
Post renal: obstruction
CKD
- Kidney damage + normal GFR >90ml/min
- Mild = 60-89 ml/min
- Mod = 30-59 ml/min
- Sev = 15-29 ml/min
- End stage =
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
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!
Skeletal defects despite normal bone profile
Pseudopseudohypoparathyroidism
Inherited
