Metabolic Flashcards
How do you calculate anion gap
(Na+K+) - (chloride + bicarbonate)
Most common organic acidaemias
Methylmalonic and propionic acidaemia
The Urea Cycle part 1
Glutamate + acetyl-CoA forms N-acetylglutamate
Enzyme = N-acetylglutamate synthetase
Urea Cycle part 2
Ammonia + bicarbonate forms carbamoyl phosphate
Only in presence of N-acetylglutamate
catalysed = carbamoyl phosphate synthetase
Urea cycle part 3
Carbamoyl phosphate + ornithine = citrulline
Where does part 1- 3 occur?
Mitochondrial matrix
Urea Cycle part 4
Occurs in cytoplasm
Citrulline + aspartate to form arginosuccinate
Urea Cycle part 5
Argininosuccinate lyase cleaves argininosuccinate to arginine
Urea Cycle Part 6
Arginine is hydrolysed to urea + ornithine
Ornithine is transported to mitochondrion for part 3
Normal ammonia levels
<100
How are urea cycle disorders inherited
Autosomal recessive
Except ornithine transcarbamylase = X-linked
Acute management of Urea cycle disorders
Stop feeds
Commence 10% dextrose to reduce nitrogen load on cycle
IV ammonia
IV arginine
Chronic management of urea cycle disorder
Low protein diet
Gluconeogenesis
Synthesis of glucose from non-glucose precursors
Glycolysis
Oxidation of glucose to pyruvate with generation of ATP
Glycogenesis
Conversion of excess glucose to glycogen
Glycogenolysis
Degration of glycogen to glucose
GSD 1
Deficiency of glucose-6-phosphate
Inability to mobilize glucose from glycogen or utilise glucose from gluoneogeneis
Why do patients with GSD have heptaomegly
Glycogen storage
Which GSD’s present with hepatic presentation
Ia
Ib
III
IV
VI IX O
Which GSD’s present with muscular presentation
V, VII, X, XI, XII, XIII
Which present with a cardiac presentation
II
III
What is the most common muscle glycogenesis
GSD 5 - McArdle’s disease
How does McArdle’s present
Muscle pain, cramps and fatigue during brief intense exercise
Resume exercise after brief rest
What is cause of McArdle’s
Lack of pyruvate available for production of acetyl-CoA for Kreb’s cycle
Defiency of my-phosphorylase enzyme -> reduced glycolysis in muscle fibres and reduced production of pyruvate
pathophysiology of PKU
Defiency of phenylalanine hydroxyls in the liver - would usually convert phenylalanine to tyrosine
Phenylalanine can cross BBB
What smell is characterisistic of PKU
Mousy odour in sweat or urine
Ix of PKU
Must be before day 10 of life to prevent neurodevelopment complications
How is PKU managed
Diet - restriction of natural proteins, low protein diet
Limit great feeding
Monitoring ohenylalanine leves
What is the gene that codes for phenylalanine hydroxyls
Chromosome 12q23.2
Which is most common fatty acid disorder
MCUD
What are the principal ketone bodies
B-hydroxybutyrate
Acetoacetate
Three stages of fatty acid metabolism
Fatty acids mobilised by lipase into mitochondria
medium and short chains permeate the mitochondrial membrane
Fatty acid oxidation disorder presentation
Hypoketotic hypoglycaemia
Cardiomyopathy, arrhythmias or conduction defects
Myopathy or acute rhabdomyolysis
When does MCAD show
Present in first few days of life
What is increased in fatty acid oxidation disorders
Carnitine and acylcarnitine levels and urine organic acids are high
Maple syrup urine disease
deifinecy in branched chain a ketoacid dehydrogenase
Dysfunction in amino acid VIL - valine, isoleucine, leucine
What causes maple syrup urine odour
Isoleucine metabolite
Pathophysiology of maple syrup disease
Increase in valine isoleucine and leucine
Interrupts large neutral amino acid transport into the brain - tyrosine and tryptophan
Less dopamine and serotonin in the brain
Pompe disease - GSD type 2 pathophysiology
Insuffiency of acid alpha- glucosidase
Lysosomes can’t break down glycogen -> glycogen build up and caused damage
Differential diagnosis of hypoketotic hypoglycaemia
Hyperinsulin - ketones negative as insulin makes body feel in fed state
MCAD
Liver failure
Mitochondria disorders
PomPe disease - Type 2 GSD enzyme defiency
alpha 1- 4glucosidase
Will have normal glucose levels
Only GSD with heart
PomPe breaks the PumP = 4 p’S
what happens if glycogen accumulates in heart liver and muscle
cardiomegaly
hepatomegaly
hypotonia
Cori disease - type 3 GSD
hypoglycemia
ketoacidosis
