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Toni's Pathology > Chem Path > Flashcards

Chem Path Flashcards

1
Q

How is osmolarity calculated?

A

2(Na + K) + urea + glucose

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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

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3
Q

Serum osmolality normal range

A

275 - 295 mmol/kg

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4
Q

Na

135 - 145

A

Extra cellular cation

Extra cellular fluid volume depends on Na concentration

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5
Q

Hyponatraemia

A

Treat underlying cause only

death

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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

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7
Q

Hyponatraemia + normal osmolality

A

Pseudohyponatraemia

A spurious sample E.g. From drip arm
Hyperlipidaemia
Hyperproteinaemia

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8
Q

Hyponatraemia + high osmolality ( >295 )

A

Due to glucose or mannitol

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9
Q

Hyponatraemia + low osmolality (

A

True hyponatraemia

Differentiate between causes using either volume status or renal involvement

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10
Q

Hypovolaemic hyponatraemia

A

Urine Na:

> 20 = diuretics, Addison’s - salt losing nephropathy

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11
Q

Euvolaemic hyponatraemia

A

Urine Na:

> 20 = SIADH, primary polydipsia, severe hypothyroidism

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12
Q

Hypervolaemic hyponatraemia

A

Urine Na:

> 20 = acute / chronic renal failure

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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

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14
Q

Addison’s disease

A

Aka primary adrenal insufficiency
Reduced aldosterone + cortisol
Increase ACTH
Hyponatraemia + hyperkalaemia + hypoglycaemia
Hyperpigmentation, postural hypotension, weight loss

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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

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16
Q

Hypernatraemia

>145

A

Clinically significant = >148
Often iatrogenic
Sx= thirst -> confusion -> seizures + ataxia -> coma

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17
Q

Hypovolaemia hypernatraemia: causes

A 
Vom/diarrhoea
Sweating
Burns
Loop diuretics
Osmotic diuresis
Renal failure
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18
Q

Euvolaemic hypernatraemia: causes

A

Tachypnoea
Sweating
Diabetes insipidous
No water

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19
Q

Hypervolaemic hypernatraemia: causes

A

Mineralocorticoid excess e.g. Conn’s

Hypertonic saline

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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
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21
Q

Causes of cranial DI

A

Head trauma
Tumour
Surgery

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22
Q

Causes of nephrogenic DI

A

I.e. ADH insensitivity
Inherited
CRF
Drugs: lithium, demeclocycline

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23
Q

Conn’s syndrome

A

Aldosterone secreting tumour

= resistant htn, hypoK, metabolic acidosis with hyperNa rarely

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24
Q

Potassium

3.5 - 5.5

A

Intracellular cation

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25
Q

Causes of hypokalaemia

A

Depletion: GI loss, hyperaldosteronism, osmotic diuresis

Shift to intracellular fluid: insulin, beta agonists, alkalosis

Rare: renal tubular acidosis, hypomagnesaemia

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26
Q

Causes of hyperkalaemia

A

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

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27
Q

What are the ECG changes in hyperkalaemia and how is it managed?

A

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

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28
Q

How do you calculate the anion gap?

A

(Na + K) - Cl - HCO3

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29
Q

What is the normal anion gap range?

A

14 - 18

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30
Q

What are causes of an increased anion gap?

A

Ketoacidosis
Uraemia
Lactic acidosis
Toxins: ethylene glycol, methanol, paraldehyde, salicylates

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31
Q

Which LFTs are raised in a hepatic picture?

A

ALT more liver specific than AST

Alcoholic liver disease: AST:ALT = 2:1
Viral liver disease: AST:ALT

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32
Q

Which LFTs are raised in an obstructive picture?

A

ALP

GGT

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33
Q

When is increased ALP seen?

A 
Cholestasis
Bone disease
Pregnancy
PBC
Prostate cancer
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34
Q

When is increased GGT seen?

A

Chronic + acute alcohol use
Bile duct disease
Metastasis

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35
Q

Acute intermittent porphyria

A

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

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36
Q

What drugs are contraindicated in porphyria?

A

Diclofenac

Co trimoxazole

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37
Q

What can cause neuro damage in porphyria?

A

5 aminolavulinic acid

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38
Q

Which acute porphyrias have skin lesions?

A

HCP: hereditary coproporphyria
Neuro visceral + skin lesions
Raised porphyrins in faeces/ urine
VP: variegate porphyria

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39
Q

Which porphyria shave skin lesions only?

A

Non-acute ones:
PCT: Porphyria cutanea tarda
Uroporphyrinogen decarboxylase deficiency
EPP: erythropoietic protoporphyria
Photosensitive, burning, itching, oedema
CEP: congenital erythropoietic porphyria

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40
Q

Hypothyroidism

A

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

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41
Q

High uptake hyperthyroidism

A

Graves: autoantibodies, women>men
Toxic multinodular goitre:
Toxic adenoma: ‘hot nodule’

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42
Q

Low uptake hyperthyroidism

A

DeQuervains: self limiting, post viral, painful goitre
Aka giant cell thyroiditis

Post partum thyroiditis

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43
Q

Treatment of hyperthyroidism

A

Beta blockers + carbimazole

Radio iodine / surgery

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44
Q

Treatment of hypothyroidism

A

Thyroxine

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45
Q

Papillary thyroid cancer

A

> 60%
30-40yrs
Req surgery +- radio iodine
Then thyroxine replacement

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46
Q

Follicular thyroid cancer

A 
25%
Well differentiated
Spreads early
Surgery +- radio iodine
Thyroxine replacement
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47
Q

Medullary thyroid cancer

A

5%
MEN 2 para follicular cells
Calcitonin

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48
Q

Thyroid MALT lymphoma

A

RF= chronic Hashimoto’s

Good prognosis

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49
Q

Anaplastic thyroid cancer

A

Rare
Elderly
Poor response

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50
Q

Cushing’s disease

A

Most common cause of Cushing’s syndrome
Pituitary tumour
Cushingoid features
High dose dexamethasone test suppresses cortisol

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51
Q

Causes of Cushing’s syndrome

A 
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
Q

Causes of Addison’s

A

AI
TB- commonest worldwide
Adrenal haemorrhage
Amyloidosis

53
Q

Presentation of Addisons

A

HypoNa + HyperK + Hypo glycaemia
Pigmentation, lethargy, depression
Ix: synACTHen test
Rx: hormone replacement hydrocortisone/ fludrocortisone if primary adrenal

54
Q

Conn’s

A

Adrenal tumour zona glomerulosa -> uncontrollable htn
HyperNa + HypoK
Ix: aldosterone:renin ratio
Rx: aldosterone antagonists= spironolactone, amiloride

55
Q

Phaeochromocytoma

A

Adrenal medulla tumour = adrenaline
Ix: plasma + 24 hr urine metadrenaline measurement/ catecholamines VMA
Rx: alpha blockade, beta blockade, bp controlled -> surgery

56
Q

HypoCa
Decr phosphate
Incr PTH
Decr vit D

A

Osteomalacia/ Rickets

57
Q

HypoCa
Incr phosphate
Incr PTH

A

Secondary hyperparathyroidism

58
Q

HypoCa
Incr phosphate
Decr PTH

A

Hypoparathyroidism

Primary= Di George
Secondary= post thyroid surgery
59
Q

HyperCa
Decr phosphate
Incr PTH

A

Primary hyperparathyroidism

Tertiary hyperparathyroidism

60
Q

Incr ALP only

A

Paget’s

Bone remodelling
Bone pain

61
Q

HyperCa
Incr albumin
Incr urea

A

Dehydration

62
Q

HyperCa

Normal ALP

A

Myeloma
Excess vit D
Sarcoid

63
Q

Hypercalcaemia

A 
Renal Stones
Bone pains
Psychic Moans
Abdominal Groans 
Polyuria 
Muscle weakness
64
Q

Hypocalcaemia

A 
Peri oral paraesthesia
Carpopedal spasm
Trousseau
Neuro-Musc excitability 
Chvostek
65
Q

Renal stones

A

Radio opaque:
Mixed 45%, oxalate 35%, phosphate 1%
Triple phosphate aka struvite 10%

Radio lucent:
Uric acid 5%, Cysteine 1-2%

66
Q

Incr amylase

A

Acute pancreatitis

Mumps

67
Q

Incr creatine kinase

A

Duchenne
Rhabdomyolysis
Statin related myopathy
MI : CK MB

68
Q

Troponin

A

Not enzyme - marker
I: 6hrs post onset chest pain
T: 12hrs post onset
Remain elevated 3-10 days

69
Q

Diagnostic criteria for MI

A

Typical Troponin or CK MB
+ one of:
Ischaemic sx, q waves, ischaemic ECG, coronary artery interv

70
Q

Phenytoin

A

Ataxia + nystagmus
Once liver saturated -> surge in serum concentration
Omit or reduce dose in toxicity

71
Q

Digoxin

A 
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
Q

Gentamycin

A

Tinnitus, deafness, nystagmus, RF
Use single daily dosing monitoring peak + trough levels
Omit or reduce dose in toxicity

73
Q

Theophylline

A

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
Q

Lipid soluble drug metabolism in the liver

A
  1. Oxidation by cytochrome p450

2. Conjugation by sulphate/gluconaride?

75
Q

Lithium

A

If taken with thiazides diuretics incr risk toxicity

Decr excretion -> incr plasma concentration

76
Q

Unfractionated heparin

A

Requires regular APTT monitoring

77
Q

Cocaine

A

Aggressive, paranoid
Tachycardia
Sudden death

78
Q

Ecstasy

A 
Feverish, confused, sweaty
Hyperthermia
Dilated pupils
Raised urea + creatinine 
High myoglobin
79
Q

Heroin

A

Depressed breathing
Collapse
6 MAM

80
Q

Atenolol OD

A

IV atropine

Glucagon

81
Q

Carbon monoxide poisoning

A 
Headache
Nausea + dizziness
Collapse
CarboxyHb
O2
Hyperbaric O2
82
Q

Paraquat consumption?

A

Activated charcoal

83
Q

Salicylate toxicity

A

Hyperventilation
Sweaty, nauseous
Ringing in ears
Mixed acid-base disturbance

84
Q

TCA toxicity

A 
Drowsy
Tachycardic
Dilated pupils
Wide QRS interval
Hyperreflexia
85
Q

Organophosphate toxicity

A 
Farmer
Nausea + vom
Headache, hypersalivation
SOB
Sweaty, flaccid paresis
86
Q

Testing for drugs

A

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
Q

Types of primary hypercholesteraemia

A

Familial T2: apoB, PCSK9, AD-LDLR, AR-LDLRAP1
Polygenic hypercholesteraemia
Familial hyper-alpha-lipoproteinaemia
Phytosterolaemia: ABC, G5 + G8

88
Q

Types of primary triglyceridaemia

A

Familial T1: lipoproteinlipase/apoC II deficiency
Familial T4: incr TG synth
Familial T5: apoA V deficiency

89
Q

Types of mixed hyperlipidaemia

A

Familial combined hyperlipidaemia
Familial dys-beta- lipidproteinaemia
Familial hepatic lipase deficiency

90
Q

Hypolipidaemia

A

A-beta-lipoproteinaemia: MTO deficiency
Tangier disease: HDL deficiency
Hypo-alpha- lipoproteinaemia: apoA1 mutations
Hypo-beta- lipoproteinaemia : truncated apo-beta-protein

91
Q

Lipoproteins in order of density

A

Chylomicron

92
Q

PCSK9

A

Binds LDLR + promotes degradation
Loss of function mutation -> low LDL levels

A novel LDL lowering Rx: anti PCSK9 mab

93
Q

Lipoprotein a

A

CVD risk factor

Rx: nicotinic acid

94
Q

Vit A

Aka retinol

A

Def= night blindness
Exc= exfoliation, hepatitis
High levels teratogenic

95
Q

Vit D

Aka cholecalciferol

A 
Def= osteomalacia
Exc= hypercalcaemia
96
Q

Vit E

Aka tocopherol

A

Def= anaemia, neuropathy, IHD

97
Q

Vit K

Aka phytomenadione

A

Def= defective clotting

Measured with PTT

98
Q

Vit B1

Thiamine

A

Def= Beri Beri, neuropathy, Wernicke’s

Measured using RBC transketolase

99
Q

Vit B2

Aka riboflavin

A

Def= glossitis

Measured using RBC glutathione reductase

100
Q

Vit B6

Aka pyridoxine

A

Def= dermatitis, anaemia
Exc= neuropathy
Measured using: RBC AST activation

101
Q

Vit B12

Aka cobalamin

A

Def= pernicious anaemia

102
Q

Vit B3

Aka niacin

A

Def= pellagra: Dementia, Dermatitis, Diarrhoea

Casal’s necklace

103
Q

Vit C

Aka ascorbate

A

Def= scurvy
Exc= renal stones
Measure using plasma

104
Q

Folate

Aka folic acid

A 
Def= megaloblastic anaemia
Exc= haemochromatosis
105
Q

Iodine

A

Def= hypothyroidism + goitre

106
Q

Zinc

A

Def= dermatitis

107
Q

Fluoride

A 
Def= dental caries
Exc= fluorosis
108
Q

Phenylketonuria

A 
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
Q

MCAAD

A

Fatty acid oxidation disorder

Test acyl carnitine levels by tandem mass spectrometry

110
Q

Mitochondrial disorders

Aka defective ATP production

A

Barth: at birth cardiomyopathy, neutropaenia, myopathy
MELAS: 5-15yrs lactic acidosis, mitochondrial encephalopathy, stroke like episodes
Kearns Sayre: 12-30yrs retinopathy, deafness, ataxia

111
Q

Homocysteinuria

A

Cystathionine synthetase deficiency
Fair skin, brittle hair, dev delay
Convulsions, skeletal abnormalities, thrombosis
Rx: vit B6 pyridoxine/ low methionine diet

112
Q

Von Gierke’s

A

Glucose-6-phosphate deficiency
Glycogen storage disorder
Hypoglycaemia, hepatomegaly, renal enlargement

113
Q

Maple syrup urine disease

A

Organic aciduria=
impaired metabolism of leucine, isoleucine, valine
Toxic encephalopathy: lethargy, poor feeding, hypotonia, seizures
Sweet odour, sweaty feet
Ix: gas chromatography

114
Q

Fabry’s disease

A 
Lysosomal storage disorder
Alpha- galactosidase deficiency
Dev delay, dysmorphia, seizures
Deafness, blindness, hepatosplenomegaly 
Cherry red spot
115
Q

Galactosaemia

A

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
Q

Other glycogen storage disorders

A

Pompe’s: lysosomal-alpha-glucosidase
Cori’s: amylo-1-6-glucosidase
McArdles: phosphorylase

All-> liver + muscle dysfunction

117
Q

Impaired glucose tolerance

A

Random glucose > 7.8 but

118
Q

DM

A

Sx + 2 of:
Fasting glucose >7
Random glucose >11.1
Oral glucose tolerance test > 11.1

(HbA1c>48)

119
Q

Impaired fasting glucose

A

Fasting glucose > 6.1 but

120
Q

Hyperinsulinaemic hypoglycaemia causes

A

Iatrogenic insulin
Insulinoma
Sulphonyl urea excess

121
Q

Hypoinsulinaemic hypoglycaemia causes

A

+ve ketones: alcohol, fasting, Addisons, liver failure, pituitary insufficiency
-ve ketones: non-pancreatic neoplasms: fibromata/sarcomata

122
Q

Normal GFR

A

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
Q

Causes of AKI

A

Pre renal: decr perfusion, no structural abnormality
Renal: vascular, glomerular, tubular, interstitial
Post renal: obstruction

124
Q

CKD

A
  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
Q

Causes + consequences of CKD

A

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
Q 
HypoCa
Incr phosphate
Incr PTH
Rounded facies
Short metacarpals
A

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
Q

Skeletal defects despite normal bone profile

A

Pseudopseudohypoparathyroidism

Inherited

Toni's Pathology (6 decks)

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