MEH Flashcards
Lactose intolerance?
Decreased ability to digest lactose: Primary - Absence of lactase persistence allele - Only in adults (lactase present in kids) Secondary - Injury to small intestine - Infants and adults - Usually reversible Congenital - AR defect in lactase gene (can't digest breast milk) - Extremely rare
Hyperlactaemia?
High lactate (2-5mM)
Below renal threshold - so kidneys can still excrete excess
No change in blood pH
Can be coped with
Lactic acidosis?
High lactate (>5mM) Above renal threshold - kidneys can no longer excrete excess Buffer can't cope with this - pH lowered Possible causes: pyruvate dehydrogenase (converts pyruvate to acetyl CoA) deficiency
Essential fructosuria?
Fructokinase missing
- leads to fructose in urine and no clinical signs
Fructose intolerance?
Aldolase missing (usually converts fructose-1-phosphate to glyceraldehyde and DHAP)
- Leads to fructose-1-phosphate accumulating in liver –> liver damage
Treatment: remove fructose from diet
Marasmus?
Occurs due to insufficient energy intake (protein, vitamins, minerals, dehydration) - form of severe malnutrition
- Mobilisation of fat stores –> fatty acids released (loss of body fat) –> converted to ketone bodies (source of energy for CNS)
- Muscle protein broken down (loss of muscle mass) –> amino acids for glucogenesis (when glycogen stores depleted)
- Signs: wizened appearance, thin limbs, GI tract affected, normochromic anaemia, pituitary hormones affected, heart muscle thins, bradycardia, hypotension, brain affected
- Treatment: reintroduce food slowly
Kwashiorkor?
Low protein intake
Body unable to synthesise some essential proteins
- Signs: leg swelling, sparse hair, moon face, flaky skin, swollen abdomen, thin muscles with fat, fatty liver –> hepatic dysfunction (lipids accumulate because lipoproteins for their transport not being synthesised), oedema (low albumin so low oncotic pressure of plasma), fatigue, poor immune function, wasting
- Treatment: Small amounts of protein at regular intervals
Refeeding syndrome?
Cancerous, anorexic patients fed huge meals after malnutrition, when nutrient and energy stores have been depleted (Especially phosphate)
- Insulin increases –> respiration –> use up phosphate –> further decreased conc. –> MI
- Ammonia toxicity due to downregulation of 5 enzymes in urea cycle - coma, confusion, death
- Should be re-fed slowly
Galactosaemia?
Rare genetic metabolic disorder that affects the ability to metabolise galactose
3 types
Symptoms: vomiting, weight loss, hepatomegaly, jaundice, possibly cataracts
Blood test to identify which type
Type 1 Galactosaemia?
Deficiency of Uridyl transferase
Usually converts galactose 1-phosphate to glucose 1-phosphate
Hence build up of galactose 1-phosphate when enzyme absent
Causes tissue damage/accumulates in liver, kidney
Treatment: galactose free diet
Type 2 Galactosaemia?
Deficiency of Galactokinase
Usually converts galactose to galactose-1-phosphate
Hence galactose builds up when enzyme absent - converted to galactitol instead by Aldose reductase (this uses NADPH –> compromised ROS defence)
Causes cataracts
Treatment: galactose free diet
Type 3 Galactosaemia?
Deficiency of UDP-galactose epimerase (most likely, most serious)
Usually converts galactose-1-phosphate to UDP-galactose (reversible reaction to make galactose-1-P from glucose)
Hence galactose-1-P builds up when enzyme absent–> tissue damage
Treatment: none, because galactose free diet would completely get rid of galactose-1-phosphate and since this isn’t being made from glucose, no galactose-1-P at all (essential)
Urea cycle defects?
AR genetic disorders - deficiency of one of 5 enzymes (partial loss)
Leads to hyperammonaemia, accumulation/excretion of intermediates
Symptoms: vomiting, lethargy, irritability, mental retardation, seizures, coma
Management: low protein diet, keto acids not amino acids
Phenylketonuria?
Deficiency in phenylalanine hydroxylase - phenylalanine not converted to tyrosine
(AR - gene on chromosome 12)
Accumulation of phenylalanine
Phenylketones in urine - musty smell
Symptoms: intellectual disability, microcephaly, seizures, hypopigmentation
Treatment: low phenylalanine diet (avoid artificial sweeteners, meat, milk, eggs)
Homocystinuria?
Defect in cystathionine b-synthase - homocysteine not converted to cystathionine (AR)
Accumulation of methionine and homocysteine
Excess homocystine in urine
Affects CT, muscles, CNS, CVS
Symptoms: lens dislocation, skeletal deformities (also in Marfan’s), neurological problems (not in Marfan’s)
Glycogen storage diseases?
Due to deficiency/dysfunction of enzymes in glycogen metabolism
11 distinct types
- von Gierke’s disease (G6-phosphatase deficiency) –> enlargement of liver
- McArdle disease (muscle glycogen phosphorylase deficiency) –> exhausted quickly
Hyperlipoproteinaemias?
Raised plasma level of one or more lipoprotein class Due to: Over-production or Under-removal caused by defects in; enzymes, receptors or apoproteins Treatment: diet, lifestyle, statins (reduce cholesterol synthesis), bile salt sequestrants (use up more cholesterol)
Type I hyperlipoproteinaemia?
Defective lipoprotein lipase causes chylomicrons to appear in fasting plasma
Type IIa hyperlipoproteinaemia?
Defective LDL receptor
Associated with severe coronary heart disease
Type III hyperlipoproteinaemia?
Defective apoE causes raised IDL and chylomicrons remanants
Quite rare
Associated with coronary heart disease
Atherosclerotic plaques?
Oxidised LDLs engulfed by macrophages -> foam cells
Accumulate in intima of blood vessels -> fatty streak -> atherosclerotic plaque -> angina, stroke, MI
Hypercholesterolaemia?
High level of cholesterol in blood Deposits in: Eyes lids (yellow patches) - xanthelasma Nodules on tendons - tendon xanthoma White circle around eye - corneal arcus Treatment: lifestyle changes initially, statins
Iron deficiency anaemia?
Due to either low intake, high loss/usage
- RBCs: hypochromic, microcytic, anisopoikilocytosis, pencils cells -> leads to anaemia
- Low serum ferritin, iron, % transferrin saturation, raised TIBC
- Tests: Ferretin, CHR
- Treatments: diet, supplements, IM/IV, transfusion (severe anaemia)
Excess iron?
Free iron - dangerous
Produce highly reactive hydroxyl, lipid radicals - damage lipid membranes, nucleic acids, proteins
Excess iron deposited in tissues (insoluble)
Haemochromatosis?
Excess iron deposited resulting in end organ damage
Causes liver cirrhosis, diabetes hypogonadism, cardiomyopathy, arthropathy, skin pigmentation
Hereditary haemochromatosis?
AR genetic disorder
Mutation in gene HFE on chromosome 6
Normally HFE competes with Transferrin to bind to receptor. Mutated-> doesn’t bind, transferrin has no competition
Too much Fe absorbed in intestine/cells -> Fe then deposited by skin, liver, pancreas, heart causing haemosiderosis
Symptoms: liver damage, heart dysfunction, pancreatic failure
Treatment: venesection/repeated bleeding
Transfusion assc. haemosiderosis?
Gradual accumulation of iron
Eg: Thalassemia, myelodysplasia
Treatment: iron cheating agents/tablets - only delay effects
Anaemia?
Inability of body to deliver enough oxygen - either not enough RBCs or not enough Hb
Due to problems in: erythropoiesis, Hb synthesis, RBC structure/metabolism, RES
Reduced erythropoiesis?
Less RBCs being produced
Due to:
-Empty bone marrow, unable to respond to EPO stimulus (after chemo). Leads to aplastic anaemia
-Marrow infiltrated by cancer cells/fibrous tissue
Chronic dyserythropoiesis?
Anaemia of chronic disease Seen in: RA, SLE, IBD, TB, bronchiectasis -Fe in macrophages not released -RBCs -> low life span -Marrow -> low response to EPO Tests: Raised CRP and Ferretin
Dyserythropoiesis - myelodysplasia?
Production of abnormal clones of marrow stem cells
Macrocyctic anaemia - RBCs destroyed by RES -> progressive anaemia -> acute leukaemia
Test: microscopy
Treatment: chronic transfusions of RBCs, chemo and stem cell transplant
B12 deficiency?
Req. for DNA synthesis etc
Leads to megaloblastic, macrocytic anaemia. Can progress to pancytopenia
Due to:
-Diet low in meat
-IF deficiency (pernicious anaemia) - AU disease, gastric parietal cells can’t produce IF
-Crohn’s etc -> IF-B12 complex doesn’t form
-Congenital deficiency in transcobalamin (delivers B12)
Can also cause neurological diseases
Folate deficiency?
Req. for DNA synthesis etc Leads to megaloblastic, macrocytic anaemia. Can progress to pancytopenia Due to: -Deficiency in diet -Increased use (pregnancy, skin diseases, haemolytic anaemia) -Coeliac disease etc -Crohn's disease drugs -Alcoholism
Sickle cell disease?
AR inherited - Val substituted for Glu in6th position of B-chain of Hb
RBCs become sickle shaped - causes anaemia
Thalassaemia?
Heterogenous group of genetic disorders - affects either A or B-chains of Hb
Low Hb levels in cells - hypochromic microcytic RBCs/anaemia
-Excessive destruction of RBCs in spleen
-Splenomegaly, hepatomegaly, skeletal abnormalities
Treatment: transfusions, Fe chelation
G6PDH deficiency?
G6PDH used in pentose phosphate pathway
Deficiency (due to genetic defect) will lead to less NADPH production -> less protection against ROS
Can lead to anaemia & jaundice: Oxidative damage to Hb -> disulphide bridges -> chains cross link > Heinz bodies -> RBCs damaged -> anaemia & jaundice
Test: bite/blister cells seen on blood film
