Chem Path Revision Notes

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Chemical Pathology Notes
Fluid Balance
- ⅔ INTRACELLULAR
- ⅓ EXTRACELLULAR
Electrolytes
Cations
 Intracellular = K+ (3.5 - 5)
 Extracellular = Na+ (135 - 145)
Anions
 Intracellular = protein and phosphate
 Extracellular = Cl- and HCO3- (22 -26)
Osmolality
“Total number of solute particles in solvent” (280-295 mosmol/l)
Calculated Plasma osmolality = 2([Na+] +[K+]) + urea +glucose
Osmolar Gap (<10) = Measured osmolality – calculated osmolality
Anion Gap (~ 18 mmol) = Na + K - Cl - Bicarbonate
Key controllers of ECF
Extra-renal System
 Stimulated by:
o Osmoreceptors
o Baroreceptors (low volume)
 Action by:
o Thirst
o Anti-diuretic hormone from posterior pituitary
o ANF (reduced sensitivity of osmoreceptors, RAA antagonism)
Intra-renal System
 Stimulated by:
o Reduced renal perfusion
 Action by:
o Renin-angiotensin-aldosterone system (positive)
o ANF (negative)
Too much fluid
 Increased intake (rarely a problem)
 Increased/inappropriate sodium
reabsorption
o Cardiac failure
o Nephrotic syndrome
Too little fluid
 Inadequate intake (during illness)
 Distribution problem
o Sepsis
o 3rd spacing

Reduced excretion
o Renal failure
o Nephritic syndrome

Excess loss
o Fluids (gut, kidneys, skin,
respiratory)
o Blood (internal vs. external)
Sx












Confusion/coma
Cool hands
Cap. Refill
Tachycardia
Tachypnoea
BP/postural drop
JVP
Sunken eyes
Dry mouth
Lungs clear
Urine output (< 30ml/hr)
No oedema
Tx
CRYSTALLOIDS
- electrolytes in water
COLLOIDS
- fluids with high molecular
weight molecules
Types
Normal saline
Dextrose saline
5% dextrose
Hartmannʼs
Natural (e.g. blood, albumin)
Synthetic (e.g. Gelofusin,
Haemaccel)
Contents
154 mmol Na+ in 1L
30 mmol/l Na+ + 40g dextrose
50g dextrose in IL
Anions + Cations + Ca + lactate
Dextran compounds
Electrolyte Disorders
Hyponatraemia
 Na+ < 135 mmol/l
Serum sodium (mmol/l)
130-135
125-130
115-125
<115
Hypovolaemia
Cause
Renal
Adrenal failure
(Addisons)
Diuretics
U. Na+
(mmol/l)
>20
Features
Asymptomatic
MILD - N/V, mild disorientation
MODERATE - confusional state
SEVERE - seizures/coma
Normovolaemia
Non-renal
Vomiting
Diarrhoea
Skin loss
<10
Hypervolaemia
Renal
ARF/CRF
SIADH
>20
>20
Syndrome of Inappropriate ADH
 Malignancy
o Small cell malignancies (lung, pancreas, lymphoma)
 Lung pathology
o TB, pneumonia, abscess
 CNS pathology
o Infections, bleeds
 Drugs (carbamezapine, chlorpropramide, cyclophosphamide, ectasy (MDMA))
Sx

↓ [Na]

Euvolaemia
Non-renal
Cardiac Failure
Cirrhosis
Nephrotic syndrome
Inappropriate IV fluid
<10


↓osmolality
↑urinary [Na]

No other cause (diagnosis of exclusion)

Increased loss (common)
o Gut (diarrhoea, vomiting, fistulae)
o Kidneys (↑mineralocorticoid,
diuretics, RTA 1 & 2)
Hypernatraemia
 Insufficient fluid intake
 Water loss increased relative to sodium loss
o DI (low urine osmolality)
o Osmotic diuresis (high urine osmolality)
o Primary aldosteronism
Hypokalaemia
 Reduced intake (rare)
 Cellular uptake
o Insulin, alkalosis
Sx:
 Generally asymptomatic
 Muscle weakness
 Reduced gut motility
 Cardiac arrhythmias
Hyperkalaemia
 Increased intake (rare)
 Cellular loss
o Acidosis, severe haemolysis/rhabdomyolysis
 Decreased loss
o Renal failure
o Decreased mineralocorticoids (RTA 4)
o Potassium sparing diuretics + NSAIDs + ACEi
Sx:
 Cardiac arrest
 Muscle weakness
Tx



Stabilise the myocardium
o 10ml 10% calcium gluconate
Drive K into the cells
o 10u insulin + 50ml 50% dextrose
o Salbutamol
Mop up K
o Calcium resonium, haemofiltration
Calcium
 Serum calcium: 2.2 - 2.6 mmol/l

Paraesthesiae
Hypocalcaemia
Ca < 2.2 mmol/l
Causes:
 Parathyroid removal


Vit. D deficiency
Renal disease
Diagnosis
 U&Es - ? Renal disease

Serum PTH
Clinical features:
 Asymptomatic
 Perioral paraesthesia
 Trousseau’s sign,



Chvostek’s sign
Prolonged QT
Cataract (chronic)

Severe
o Calcium gluconate infusion




Vit. D intoxication
Diuretic therapy
Tertiary hyperparathyroidism
Milk-alkali syndrome

Osteitis fibrosa cystica
Treatment
 Mild
o Calcium supplements
 In renal failure
o Alphacalcidol
Hypercalcaemia
Ca > 2.6mmol/l
Causes:
 1° Hyperparathyroidism
 Myeloma
 Bony mets
 PTH-related protein
 Granulomatous disease (TB, sarcoid)
Sx:

Asymptomatic



Nephrogenic DI (thirst, polyuria etc)
Renal stones
Abdominal symptoms (vomit,
constipation, pain)



Weakness
Fatigue
Confusion
Treatment
 3.5 = MEDICAL EMERGENCY
 Fluids (0.9% normal saline) - promote diuresis
 Bisphosphonate - inhibit further bone resorption
 Others: surgery, steroid for sarcoid
Acid-base balance
pH
pCO2
pO2
HCOBase excess
Normal range
7.35 - 7.45
4.5 - 6
11-14
22 - 26
-2 to +2
Metabolic Acidosis
↑[H+] = pCO2
↓[HCO-]
Metabolic Alkalosis
↓[H+] = pCO2
↑[HCO-]
Respiratory Acidosis
↑[H+] = ↑pCO2
[HCO-]
Respiratory Alkalosis
↓[H+] = ↓pCO2
[HCO-]
Hydrogen ions are buffered by:
Bicarbonate
H++HCO3- ↔ H2CO3
Haemoglobin
H+ + Hb- ↔ HHb
Phosphate
H++HPO4- ↔ H2PO4
Renal Function Tests
GFR



“Volume of unit plasma that can be completely cleared of marker substance per unit time.”
Normal = 60 - 120 ml/min
Varies considerably (1ml/min per year)
Urine Microscopy
 White blood cells
o Infection
o Sterile pyuria - partially treated UTI or stone/tumour
 Bacteria
o Infection
 Hyaline casts (normal mucoprotein)
o Healthy
 Red cell casts
o Glomerulonephritis/severe tubular damage
 White cell casts
o Pyelonephritis/glomerulonephritis

Crystals
o Calcium oxalate (75%) - spikey and radio-opaque [metabolic/idiopathic]
o Triple phosphate (17%) - large, radio-opaque may form staghorn calculus [proteus UTIs]
o Uric acid (5%) - smooth, brown, radio-lucent [hyperuricaemia]
o Hydroxyapatite (1%)
o Cysteine (1%) - yellow, crystalline, semi-opaqe [renal tubular defects, cystinuria]
Liver Function Tests
Test
Bilirubin (total)
Direct Bilirubin (conjugated)
Alkaline phosphatase
Aspartate transaminase
Alanine transaminase
Albumin
-glutamyl transpeptidase
Albumin
-globulin
Prothrombin time
Normal Values
5 – 17 mol/L
< 5 umol/L
35 – 130 iu/L
5 – 40 iu/L
5 – 40 iu/L
35 – 50 g/L
10 – 48 iu/L
35 – 50 g/L
5 – 15 g/L
12-16 seconds
Congenital Syndromes
Condition
Crigler- Najjar
Inheritance
AR
Gilbert’s
Variable
Dubin-Johnson
AR
Rotor (D-J subtype)
AR
Abnormalities
↑ with choleostasis
↑when hepatocytes die
(ischaemia, toxins, viruses)
↓in sepsis, malnutrition, chronic LD
↑ with ETOH & phenytoin
Deficiency
Bilirubin metabolism
(UGT1A1)
↓ glucoronyltransferase
activity
Defective anionic
conjugate transfer
Unknown
Presentation
Hyperbilirubinaemia
+/- Kernicterus
↑bilirubin
N. liver chemistry
Asymptomatic/no
abnormal LFTs
↑Urine coproporphyrin
Unpigmented liver
Uric acid metabolism
 Plasma concentrations.
o Men 0.12 – 0.42 mmol/l
o Women 0.12 – 0.36 mmol/l
Gout
 Monosodium urate crystals
 Men>women
Clinical features
 Exquisite pain
 Red, hot and swollen joint

1st MTP joint is classical

Allopurinol for chronic episodes
Diagnosis
 Negatively birefringent crystals
Treatment
 NSAIDS are the first line treatment acutely
 Colchicine lowers urate levels
Pseudogout
 Pyrophosphate crystals
 Self limiting 1 – 3 weeks
 Positively brefringent crystals
Endocrine Investigations
Condition
Cushing’s Syndrome (↑Cortisol)
Causes
Pituitary (Micro/macroadenoma)
Adrenals (Adenoma/carcinoma)
Malignancy
Exogenous steroids
Diagnosis
Midnight plasma cortisol
Low dose DEXA test
Salivary cortisol
Urinary free cortisol
Conn’s Syndrome (↑Aldosterone)
“Hyperfunction of aldosterone
secreting cells”
Adenoma, carcinoma, hyperplasia
Plasma aldosterone ↑
Plasma renin ↓
Addison’s Disease (↓Cortisol)
Short Synacthen test
Thyroid Disease
TSH
T3
+/- thyroid autoantibodies
Protein Markers
Protein
CRP
α-1 anti-trypsin
Transferrin
Caeruloplasmin
Function
Acute phase protein
Prevents neutrophil elastase activation
Plasma Fe Transport
Contains Cu
Mops-up superoxide radicals
Ferritin
Haptoglobin
β2-microglobulin
Information
Peaks at 48h
↓ in emphesema & cirrhosis
Deficiency in Wilson’s disease
↓ in IDA,
↑ in Fe overload & acute inflammation
↓ in haemolysis
MHC Class I component
Nutrition
Fat Soluble Vitamins
A Retinol
D Cholecalciferol
E Tocopherol
K Phytomenadione
Deficiency
Colour Blindness
Osteomalacia/rickets
Anaemia/neuropathy
?malignancy/IHD
Defective clotting
Excess
Exfoliation Hepatitis
Hyper-calcaemia
Test
Serum
Serum
Serum
PT
Water Soluble Vitamins
B1 Thiamin
B2 Riboflavin
B6 Pyridoxine
B12 Cobalamin
C ascorbate
Folate
Niacin
Deficiency
Beri-Beri, Neuropathy
Wernicke Syndrome
Glossitis
Dermatitis/Anaemia
Pernicious anaemia
Scurvy
Megaloblastic Anaemia
Neural tube defect
Pellagra
Excess
Neuropathy
Renal stones
Test
RBC transketolase
RBC glutathione reductase
RBC AST activation
Serum B12
Plasma
RBC, folate
Trace Elements
Iron
Iodine
Zinc
Copper
Fluoride
Deficiency
Hypochromic Anaemia
Goitre Hypothyroid
Dermatitis
Anaemia
Dental caries
Excess
Haemochromatosis
Test
FBC, Fe, Ferritin,
TFT
Wilson’s
Flourosis
Cu, Caeroplasmin
Metabolic Disorders
Disorder(s)
Amino acid disorders
Organic acidurias
Urea cycle defects
Carbohydrate disorders
Peroxisomal disease
Mitochondrial disease
Examples
Autosomal recessive
defect in metabolism of
single amino acid
Defective late
metabolism of single
amino acid (usually
branched)
Deficiency of an enzyme
involved in the urea
cycle → build up of
ammonia
Alteration of
carbohydrate cycling in
the cell
Disorders of lipid
metabolism where there
are empty cell
persoxisomes
Mutations in
mitochondrial DNA.
Most serious when
affects muscle, brain.
Defect
PKU (↑ phenylalanine)
Homocystinuria (↑
Methylmalonic
acidaemia, Propionic
acidaemia, Isovaleric
acidaemia, Maple syrup
urine disease
6 disorders e.g.
arginaemia, citrullinemia
Lactose intolerance
Gycogen storage
disorders
Zellweger syndrome
Clinical characteristics
Failure to thrive
Seizures
Musty skin odour
Developmental delay
Organic acids in urine
sample
Encephalopathy
Irreversible neurological
damage
Hypoglycaemia
Lactic acidosis
Cataract formation
Liver/kidney problems
Hypotonia
Seizures
Mitocondrial myopathies Lots
e.g. diabetes mellitus
and deafness, Leber’s
hereditary optic
neuropathy
Lysosomal storage
disorders
Various defects in
lysosomal function that
lead to accumulation of
toxic substances
Gauncher’s disease
Niemann-Pick disease
Tay-Sachs disease
Present late (adulthood)
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