| Addisons disease | Destruction of entire adrenal cortex
• Deficiency of all hormones
• Mineralocorticoids
• Glucocorticoids
• Sex steroids
Clinical features
• Weight loss
• Anorexia
• Malaiseh
• Weakness
• Fever
• Depression , amenorrhoea, low libido, abdominal pain, myalgia, arthalgia, nausea.
Specific clinical features: Pigmentation ACTH, Postural hypotension mineralocorticoid, 90% presentations.
Biochemical features: Low sodium, hig |
| Ornithine transcarbmylase (OCT) defiency (problems with urea cycle | severe defect in the urea cycle
Severe urea cycle disorders → symptoms within 1 day of birth. If untreated child will die.
• Mild urea cycle enzyme deficiencies may not show symptoms until early childhood
Management:
Low protein diet
Replace amino acids in diet with keto acids
Severity depends on: nature of defect and amount of protein eaten. |
| Marasmus | Overall nutrient deficiency, no swollen abdomen, mainly in children. Due do decreases in carbs, proteins, minerals and vitamins. |
| Kwashiorkor | Protein deficiency, resulting in oedema. Appearance shows swollen abdomen. Present with stunted growth, decreased fat muscle mass, enlarged liver, anaemia. |
| Essential Fructosuria | Caused by a deficiency of the enzyme hepatic fructokinase is a clinically benign condition characterized by the incomplete metabolism of fructose in the liver, leading to its excretion in urine. |
| Fructose intolerance | deficiency of the enzyme fructose-1-phosphate aldolase, this enzyme is important in the breakdown of fructose by the body to be used as energy.
Results in accumulation of fructose 1- phosphate in the liver. Increased unbroken down glucose, results in water to travel into the lumen, thus resulting in diarrhoea.
symptom - poor feeding as a baby, vomiting, nausea and abdominal pain
treatment- elimination of sucrose and fructose from diet |
| Galactosaemia (Difference between the two causes) | Galactokinase deficiency non classical:
Rare, deficiency of Galactokinase, Increased galactose in blood, urine (galactosuria), increased accumulation within cataracts.
GALT (galactose-1-phosphate uridylyl transferase) deficiency:
Less Rare, Deficiency in GALT, leading to Galactosuria, galactosaemia,galactose-1-p and galactitol accumulate causing cataracts, brain and liver damage . Galactitol formation depletes tissues of NADPH and raises osmotic pressure - structure damage
Symptoms include- cirhossis, hepatomegaly, renal failure, voimiting, seizures, brain damage, hypoglycaemia.
TREATMENT - dietary restriction (lactose and galactose) |
| G6PDH deficiency | - reduced activity of G6PDH
- x linked defect
- decrease enzyme lowers levels of NADPH
- RBC are most affected as pentose pathways is the only way to generate NADPH
-
- oxidative damage occurs
- haemoglobin and other proteins become crosslinked via disulphide bonds forming oxidised SH groups
- form insoluble aggregates called Heinz bodies
- attach to RBC membrane
- kill RBC causes haemolysis
- asymptomatic unless chemicals i.e. antimalarials and foods, infections or stress.... |
| PDH deficiency | Rare X-linked genetic defect in PDH, but the most common cause of congenital lactic acidosis
No pyruvate conversion to Acetyl-CoA
• Pyruvate cannot be processed and is reduced to lactate or converted to amino acids
• Presents at birth with neurodegeneration, muscle abnormalities and may cause death in neonatal period
• Management includes dietary restriction of carbohydrates and proteins, and vit. B supplement. This reduced the amount of lactic acids formed due to less pyruvates produced. |
| Glycogen storage disease what are the two types | • Excess glycogen storage can lead to tissue damage: E.g. Von Gierke disease- liver glucose 6 phosphatase deficiency (hypoglycaemia, enlarged liver)
• Insufficient glycogen degradation can lead to hypoglycaemia and poor exercise tolerance: E.g. McArdle disease- muscle glycogen phosphorylase deficiency (exercise-induced muscle pain and cramps) |
| what are the main presentations of lyperlipoproteinaemia | - raised plasma level of one or more lipoprotein classes
- cuased by over-production and under-removal
- can be a defect in enzymes (LPL), receptors (LDLr), apoproteins (apoE") |
| what are the 5 main classes of lyperlipoprteinaemia and which ones are accosiatd with coronary artery disease | see picture |
| hypercholestrolaemia | high levels of cholestrol in blood
signs
- xanthelasma
- tendon xanthoma
- corneal arcus
treatments
diet (increase fiber intake and decrease colestrol)
lifestyle (decrease smoking increase excersise)
DRUGS
statins(inhibits HMG-CoA reducase)
bile salts/acid sequestrants |
| what are the 9 essential aa | isoleucine
lysine
threonine
histidine
lucine
methoinine
phenylalanine
trypotophan
valine |
| what aa 3 amino acids required in diet in pregnacy and in children | argine, tyrosine and cystenine |
| name 2 glucogenic, ketogenic and both amino acids | ketogenic - lysine, leucine
glucogenic - glycine and arinine
both tryptopham, tyrosine |
| cushings syndrome | excessive breakdown of protein due to excess cortisol. weakens skin leads to straie formation |
| alwhat are the two important diagnosistic mnarkers in liver failure | Alanine aminotransferase (ALT) --> alanine to glutamate
Asparate aminotransferase (AST) --> asparate to glutamate |
| refeeding syndrome | can occur when nutritional support given to severely malnourished patients
ammonia toxicty significant factor (urea ccyle down regulated)
refeed at 5-10kcal/kg/day. raised gradually to full needs within a week.
BMI <16
unintentional weight loss >15% in 3-6 months
10 days or more with limited or no nutritial intake |
| Ornithine transcarbmylase (OCT) defiency (problems with urea cycle | severe urea cycle disorders ---> symptoms within 1 day of birth. If untreated child will die
Mild urea cycle enzyme deficiencies may not show symptoms until early childhood
- managment
low porteins diet
symptoms
vomiting
letharygy
irritability
mental retardation
seizures
coma |
| PKU | no phenylaline hydroxlase
prevents phenylalanie convertion to trysine
- affected pathways
- noradrenaline
- adrenaline
- dopamine
- melanin
- thyroid hormone
- portein synthesis
symptoms
- severe intelectual disability
- developmental delay
- microcephaly (small head)
= seizures
- hypopigmentation Autosomal recessive within chromosome 12, accumulation in phenylalanine in tissues, plasma and urine. Musty smell |
| Homocystinuria | • Rare (incidence ~1 in 344,000)
• Defect in cystathionine β-synthase (CBS) is the most
common (defect in methionine synthase also possible)
• Autosomal recessive disorders
• Excess homocystine(oxidised form of homocysteine) excreted in urine
• Accumulation of homocysteine and methionine causes disease symptoms |
| Alcoholic liver disease | Liver toxicity due to acetaldehyde accumulation which leads to liver damage and dysfunction
• Altered liver metabolism due to decrease in NAD+/NADH ratio and increased availability of acetyl CoA
Consequences include:
• Escape of liver enzymes (e.g. ALT, AST and gamma glutamyl transpeptidase) to blood
• Reduced taking up and conjugation of bilirubin leading to hyperbilirubinaemia
• Reduced production of urea leading to hyperammonaemia
• Reduced synthesis of proteins (albumin, clotting factors and lipoproteins) |
| Hypopituiatarism | Gonadal deficiencies: loss of libido and secondary sexual hair, amenorrhoea, erectile dysfunction, period irregularities
GH deficiency: growth failure in children and impaired wellbeing in adults
TSH deficiency: weight gain, dry skin and cold intolerance
ACTH deficiency: mild hypotension, hyponatraemia |
| Addisons disease | Destruction of entire adrenal cortex
• Deficiency of all hormones
• Mineralocorticoids
• Glucocorticoids
• Sex steroids
Clinical features
• Weight loss
• Anorexia
• Malaise
• Weakness
• Fever
• Depression , amenorrhoea, low libido, abdominal pain, myalgia, arthalgia, nausea.
Specific clinical features: Pigmentation ACTH, Postural hypotension mineralocorticoid, 90% presentations.
Biochemical features: Low sodium, high potassium, high urea, low glucose. |
| Hypoadrenal crisis | Hypotension, Hypoglycaemia, Hyponatraemia, Hyperkalaemia, Sever dehydration, Death if untreated
Treatment: Acute presentation is a medical emergency, long term treatment necessary, Hydrocortisone 20-30mg daily (ammunocortisol replacement), Fludrocortisone 50-300ug daily
Confirmatory tests:
• 0900 cortisol (peak cortisol) should be 300
• Short synacthen test
• ACTH
• Plasma renin
• Adrenal antibodies |
| Hypothyroidism | see picture |
| Heinz bodies | See picture |
| Why Alcoholics May Have a Fatty Liver? | • Reduced levels of NAD + in liver for fatty acid oxidation
• Increased levels of acetyl CoA will not be oxidised due to reduced levels of NAD+
• Increased fatty acid synthesis and ketone synthesis (may lead to ketoacidosis) from acetyl |
| Why Alcoholics May Have Fasting Hypoglycaemia and Gout? | • Liver cells unable to use lactate and glycerol for de novo synthesis of glucose (+ poor diet - low glycogen levels)
• Reduced levels of NAD+ in liver for conversion of lactate to pyruvate and for glycerol conversion to DHAP
• Increased blood lactate leads to lactic acidosis and reduces the kidney’s ability to excrete uric acid; as uric acid levels increase, crystals of urate accumulate in tissues leading to gout |
| Hypercalcaemia | Stones, moans (depression) and groans (abdominal pain)
Treatment includes fluids as patients have lost excess fluid in urine and need circulating volume restoring.
Hypercalcaemia, signs and symptoms
CNS: altered behaviour: lethargy, depression, decreased alertness, confusion and coma
GI: anorexia, constipation, nausea and vomiting
Renal: diuresis, dehydration, risk for kidney stones.
Skeletal: increased bone resorption, fracture risk, joint pain
Cardiovascular: cause/exacerbate hypertension
Largely explained by decreased nerve excitability or calcium precipitation |
| Hypocalcaemia, clinical signs and symptoms | Neuromuscular: Tetany - involuntary muscle contraction
Paresthesia – strange sensations eg numbness/tingling
Twitching esp. face (cranial nerve)
Muscle group contraction eg clawed hands
Full blown convulsion, respiratory arrest and death
CNS: irritability, seizures, personality changes, impaired cognition
Cardiovascular: QT prolongation on ECG |
