Lipoprotein Metabolism, Metabolic Disorders, Hyper/Hypo Glycaemia, Flashcards
Lipoprotein Metabolism
page 76 in path guide has a great flow chart for this, not sure how to put photos on here so feel free to add if you would like. i will put it into words for anyone who wants it though…
fats in diet are absorbed in the small intestine to form Chylomicrons - converted via LPL to Remnants -> Liver where they are converted to vLDLs. vLDLsconvert to LDLs via LPL and HPL or go to adipose tissue and then back to the liver via FFA and albumin
Lipoproteins in order of density
Chylomicron FFA vLDL IDL LDL HDL
PCSK9…what does it do?
ProProtein Convertase Subtilisin/Kexin type 9
-Binds LDLReceptor (which breaks down LDL) and promotes its degradation
-Loss of function mutation of PCSK9 -> low LDL levels
Novel form of LDL-lowering therapy is Anti-PCSK9 MAb
Fat soluble Vitamins
A - retinol
D - Chole-calciferol
E - Tocopherol
K - Phytomenadione
Fat soluble Vitamins - A - Retinol
- Deficiency?
- Excess?
- Test?
- Colour blindness
- Exfoliation, Hepatitis
- Serum
Fat soluble Vitamins - D - Chole-calciferol
- Deficiency?
- Excess?
- Test?
- Osteomalacia/ Rickets
- Hypercalaemia
- Serum
Fat soluble Vitamins - E - Tocopherol
- Deficiency?
- Test?
- Anaemia/ Neuropathy, ?malignancy/IHD
- Serum
Fat soluble Vitamins - K - Phytomenadione
- Deficiency?
- Test?
- Defective clotting
- PTT
Water soluble vitamins
B1 - Thiamin B2 - Riboflavin B6 - Pyridoxine B12 - Cobalamin C - ascorbate Folate B3 Niacin
Water soluble vitamins - B1 - Thiamin
- Deficiency?
- Test?
- Beri-Beri, Neuropathy, Wernicke Syndrome
- RBC tranketolase
Water soluble vitamins - B2 - Riboflavin
- Deficiency ?
- Test?
- Glossitis
- RBC glutathione reductase
Water soluble vitamins - B6 - Pyridoxine
- Deficiency?
- Excess?
- Test?
- Dermatitis/ anaemia
- Neuropathy
- RBC AST activation
Water soluble vitamins - B12 - Cobalamin
- Deficiency?
- Test?
- Pernicious anaemia
- Serum B12
Water soluble vitamins - C - ascorbate
- Deficiency?
- Excess?
- Test?
- Scurvy
- Renal Stones
- Plasma
Water soluble vitamins - Folate
- Deficiency?
- Test?
- Megaloblastic anaemia, Neural tube defect
- RBC folate
Water soluble vitamins - B3 Niacin
- Deficiency?
-Pellagra - 3Ds …
…Dementia
…Dermatitis
…Diarrhoea
Trace elements - Iron
- Deficiency?
- Excess?
- Test?
- Hypochromic anaemia
- Haemochromatosis
- FBC, Fe, Ferritin
Trace elements - Iodine
- Deficiency?
- Test?
- Goitre, Hypothyroid
- TFT
Trace elements - Zinc
- Deficiency?
- Dermatitis
Trace elements - Copper
- Deficiency?
- Excess?
- Test?
- Anaemia
- Wilson’s Disease
- Cu, Caeroplasmin
Trace elements - Fluoride
- Deficiency?
- Excess?
- Dental caries
- Flourosis
Current UK screening of Metabolic Disorders and the tests carried out
1) Phenylketonuria - Guthrie Test
2) Congenital hypothyroidism - Test TSH levels
3) Cystic Fibrosis - Test immune reactive trypsin, if + = DNA mutation detection
4) Sickle cell disease
5) Medium Chain AcylCoA dehydrogenase Deficiency - test Acylcarnitine levels by tandem Mass Spectrometry
Urea Cycle Disorders
- Inheritance
- Red Flags
- Treatment
- Autosomal recessive ( except for Ornithine Transcarbamylase Deficiency - X linked)
- Red flags
- Vomiting without diarrhoea
- Hyperammonia and Resp Alkalosis
- Encephalopathy
- Change in diet
- Remove ammonia. Reduce ammonia production
Organic Acidurias - what is it?
A group of metabolic disoders that disrupt amino acid metabolism, particularly branched amino acids (leucine, isoleucine and valine)
Organic Acidurias - Neonates - presentation and Bloods
Presentation
-Unusual odours, lethargy, feeding problems
- Truncal hypotonia/Limb hypertonia, myoclonic jerks
Bloods
- Hyperammonia with metabolic acidosis and high anion gap (not lactate)
- Hypocalcaemia, Neutropenia, Thrombopenia, Pancytopenia
Organic Acidurias - Chronic Intermittent forms of fatty acid oxidation. Present with Recurrent episodes of …
Ketoacidotic coma
Cerebral abnormalities
Reye Syndrome
- Vomiting, lethargy, confusion, seizures, decerebration, resp arrest
- Triggers = salicylates, antiemetics, valproates
Galactosaemia - what is it?
Glucose-1-phosphate uridylyltransferase deficiency (GAL-1-PUT) is the most severe of the 3 unknown disorders. Raised Gal-1-PUT causes liver and kidney disease
Galactosaemia - Presentation
Vomiting, diarrhoea, conjugated hyperbilirubinaemia, hepatomagaly, hypoglycaemia and sepsis
Galactosaemia - Lab investigations
Urine reducing substances, Red cell GAL-1-PUT
Glycogen storage disorders - what is it? due to? leads to?
A result of defects in glycogen synthesis or breakdown. Commonly have muscular, liver and other consequences.
11 types altogether, all due to enzyme deficiencies. GSD type 1 (von Gierke’s disease) is glucose-6-phosphatase deficiency
Leads not only to excessive glycogen storage but also prevents glucose export from gluconeogenetic organs
Glycogen storage disorders - Presentation
Lactic acidosis Convulsions Hypoglycemia (Irritability, pallor, cyanosis, hypotonia, tremors, loss of consciousness and apnea) Hepatomegaly Hyperlipidaemia Hyperuricaemia Neutropaenia
Lysosomal Storage Disease
- what is it? what does it lead to?
- Lab invetigations?
- Treatment?
- Intraorganelle substrate accumulation leading to organomegaly and consequent dysmorphia and regression.
- Lab Investigations - Urine mucopolysaccharides and Oligosaccharides, Leucocyte enzyme activity
- Treatment - Bone Marrow transplant, exogenous enzymes
Peroxisomal Disorders
Disorder in metabolism of very long chain fatty acids and biosynthesis of complex phospholipids
Peroxisomal Disorders in Neonates - symptoms
- Severe muscular hypotonia, seizures
- Hepatic dysfunction - mixed hyperbilirubinaemia
- Dysmorphic signs
Peroxisomal Disorders in Infants - symptoms
- Retinopathy (often leading to early blindness), sensorineural deafness, mental deficiency
- Hepatic dysfunction
- Large fontanelle, osteopenia of long bones, calcified stippling
Peroxisomal Disorders - Lab investigations
Very long chain fatty acids
Mitochondrial disorders - what is it?
Defective ATP production leads to multi systemic disease especially affecting organs with a high energy requirement such as brain, muscle, kidney, retina and endocrine organs
Mitochondrial disorders - age, disorder, presentations?
- Birth - Barth Disorder - Cardiomyopathy, neutropenia, myopathy
- 5-15 years - MELAS Disorder - Mitochondrial Encephalopathy, Lactic acids and stroke-like episodes
- 12-30 years - Kearns Sayre Disorder - CPEO, retinopathy, deafness, ataxia
Diabetes Mellitus
- Diagnosis?
- HbA1C?
- GTT?
- Fasting Glucose?
- 90% T2DM
- Diagnosis - made with either typical symptoms plus one off fasting glucose >7, OGTT >11.1 or random glucose >11.1 or made without symptoms via 2 tests
- HbA1C >48
- Random/Oral GTT >7.8 but 6.1 but
Hypoglycaemia - classification
1) Hyperinsulinaemic hypoglycaemia - Iatrogenic insulin, sulfonylurea excess, insulinoma
2) hypoinsulinaemic hypoglycaemia
a) +ve Ketones - Alcohol binge no food, Pituitary insufficiency, Addison’s, Liver failure
b) -ve Ketones - Non Pancreatic neoplasms - Fibrosarcomata, fibromata
Causes of Hypoglycaemia with low insulin and C-peptide in Adults?
Adults
- Fasting
- Strenuous excerise
- Critical Illness
- Endo deficiency - Hypopit, adrenal failure
- Liver failure
- Anorexia Nervosa
Causes of Hypoglycaemia with low insulin and C-peptide in Neonates?
Ketones present
- Premature
- IUGR
- Co morbidity
Ketones absent
-Inherited Metabolic Disorder
Causes of Hypoglycaemia with high insulin?
Endogenous Cause
- Insulinoma - requires -ve sulphonylurea screen
- Quinine
- Pentamidine
Non-Islet tumour hypoglycaemia
LOW Glucose, insulin, C-peptide, FFA, Ketones
Tumours that can cause a paraneoplastic syndrome, secreting Big IGF-1, which binds to IGF-1 and Insulin receptors
