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181 Cards in this Set
- Front
- Back
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Which region does Crohn's disease normally affect?
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Terminal Ileum
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What % UK people obese?
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20%
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How many Diabetics? How many with Type II?
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3 000 000
90% |
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How many are unaware they have diabetes?
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750 000
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How is BMI calculated
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Weight / Height^2
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What is the the pancreatic rich in and how does this assist its function?
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- Contains Protease / Amylase / Lipase
- Rich in HCO3- which neutralises duodenal content |
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What are the four main layers of the stomach?
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- Mucosa
- Submucosa (venules/arterioles) - Muscalaris - Serosa |
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What is the function of stomach G cells?
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To secrete hormone gastrin
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What is the function of stomach Chief cells?
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To secrete pepsinogen and gastric lipase
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What is the function of stomach Parietal cells?
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To secrete HCl and Intrinsic factor
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What is the function of stomach Mucous Neck & Surfac Mucous cells?
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To secrete mucus
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Which three chemical messengers regulate parietal HCl release?
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- Aetylcholine
- Histamine - Gastrin |
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What are salivary glands?
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Compound organs secrete electrolytes & proteins as fluids into oral cavity
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What is the COMA?
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Commitee of Medical Aspects of Food Policy
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What are macro nutrients?
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- Lipids
- Carbohydrates - Proteins - Alcohol |
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What are micro nutrients?
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- Essential Minerals
- Essential Amino Acids - Essential Fatty Acids |
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What does DRV stand for?
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Dietary Reference Values
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What does EAR stand for?
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Estimated Average Requirement
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What does RNI stand for?
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- Reference Nutrient Intake
- 2 x SD above EAR |
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What does LRNI stand for?
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- Lower reference Nutrient Intake
- 2 x SD below EAR |
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What is the average salt intake per day?
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9g
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What is the max salt required per day?
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6g
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What is Leptin & what is its function?
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Leptin is a hormone produced by fat cells and released into the plasma where its concentration is proportional to fat store size. Leptin controls hunger.
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What does Insulin signal?
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Fullness of carbohydrate stores
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Where in the brain do satiety signals lead to?
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Hypothalamus
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What is Neuropeptide Y?
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Neurotransmitter produced in Hypothalamus; the main effect of NPY is to promote increased food intake and decreased physical activity in response to a plummeting blood sugar level. NPY determines how many calories stored as fat.
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What is Ghrelin?
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Hormone produced mainly by P/D1 cells lining the fundus of the human stomach & epsilon cells of the pancreas that stimulates hunger
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Name a POMC related peptide which suppresses appetite.
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PYY 3-36
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Causes of obesity in relation to leptin?
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- [Leptin] higher in obese
- Leptin resistance |
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Endocrinological causes of obesity?
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- Adrenal hyperactivity
- Hyperthyroidism |
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What is UK DoH fatty acid recommendation?
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2-5g/day
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What is the average uk diet fatty acid content?
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8-15g/day
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High intake of which fatty acids may provide additional protection against CV disease?
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Omega-3 (fish oils)
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How many UK people die from CVD every year?
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250 000
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Which fatty acids can lower blood cholesterol to some extent?
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Polyunsaturated
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What is a cis fatty acid?
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Kink
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What is trans fatty acid?
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Straight
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What is sorbitol (monosaccharides) used for?
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Commercially prepared mainly in foods for diabetics
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Where can inositol be found?
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In fibre as hexaphosphate & interferes with absorption of iron & calcium
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What is the protein requirement?
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0.75g / kg / day
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What is NSP?
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- Non-Starch Polysaccharides
- 'Fibre' - Low in energy high in bulk |
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What are essential amino acids required for?
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- Synth new protein
- Catecholamines / Neurotransmitters - Thyroid Hormones - Haem - Glutathione |
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What does PEM stand for?
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Protein Energy Malnutrition
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What is a homemade ORS?
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- 8 Teaspoon sugar
- 1 Teaspoon salt - 1 Litre boiled water |
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What is the definition of a vitamin?
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A complex organic substance required in the diet in small amounts whose absence leads to a deficiency disease
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Which vitamins are water-soluble?
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B & C
- Not stored extensively |
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Which vitamins are fat-soluble?
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A & D & E & K
- Not absorbed - Easily stored |
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What is another name for vitamin B1?
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Thiamin
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What is another name for vitamin B2?
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Riboflavin
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What is another name for vitamin B3?
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Niacin
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Which enzyme complex is directly affected by vitamin B?
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Pyruvate Dehydrogenase
- Leads to accumulation |
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What are the effects of a thiamin deficiency?
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- Heart Failure
- Neuropathy - Infantile / Acute / Chronic Beri Beri |
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Why do alocholics suffer many Vit B deficiencies?
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- Adequate energy
- Inadequate level vitamin / nutrients |
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What is the function of Riboflavin?
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- FAD/FMN in redox
- UV sensitive |
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What is Pellagra?
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- Vitamin B3 Deficiency
- Dermatitis - Diarrhoea - Dementia |
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Which AA can Niacin be formed from?
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Tryptophan
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What is Niacin linked with?
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NAD & NADP in redox
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What is the function of VItamin E?
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- Prevents oxidation of FA in cell membranes
- Poly-unsat fat susceptible to free radical attack & Vit E terminates chain reaction |
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What neurological changes arise from a deficiency in Vitamin B12 (Cobalamin)?
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- Spinal Cord / Brain lesions
- Loss of positional sense / Unsteadiness - Limb Numbness |
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Why are all pregnant women attending ante natal prescribed B12 supplements?
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UK one of world's highest rates of neural tube defects
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For what protein conversion is B12 required for?
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Homocystein to Methionine
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What is the metabolic function of folate?
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Purine / Pyrimidine Synthesis
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What is the Vit B12 DRV and what are its main sources?
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- 50μg/day
- Whole grains / Liver / Green Vegetables |
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Which glycoprotein does B12 bind to?
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Intrinsic Factor released from Gastric cells
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What is the active form of Folate? What does Folate carry?
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- Tetrahydrofolate
- Methyl groups during metabolism |
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What is the function of Pyridoxine (B6)?
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- AA metbolism
- Haem Synthesis |
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What is the disadvantages of treating TB patients with Isoniazid?
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- It combines with the active form of B6 Pyridoxal Phosphate
- Patients given B6 supplements |
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What is the most common cause of B6 deficiency?
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Presence of antagonists (Secondary deficiency)
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What are the therapeutic uses of Vitamin B6?
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Autism / Down's Syndrome / Seizures / Pre-Menstrual Tension Syndrome (Can cause peripheral neuropathy)
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What is neuropathy?
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Disease or dysfunction of one or more peripheral nerves, typically causing numbness or weakness.
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What are the main sources of B5 & how does that impact its deficiency prevalence?
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- Source ubiquitous (everywhere)
- Deficiency is rare |
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What is the function of B5 (Pantothenic Acid)?
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Component of CoASH in carbon metabolism
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What is the primary cause of Biotin (B7) deficiency?
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Long term antibiotic use
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What is the metabolic use of B7?
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Prosthetic group for carboxylations
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What is the function of Ascorbic Acid (C)?
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- Hydoxylation of lysine & proline in collagen formation
- Anti-Oxidant nutrient |
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Why do smokers need 2x normal intake? of Ascorbic Acid?
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The vitamin C turnover is increased by smoking
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What are the risk of megadoses?
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- Oxalate kidney stones
- Diarrhoea - Systemic conditioning - Pregnant women give birth to babies with shifted calibration for higher requirements |
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How is Vitamin A stored / transported?
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- Gut -> Liver in chylomicrons
- Liver -> tisses bound to specific retinol binding protein & pre-albumin |
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Pregnant women should not take which vitamin supplements / eat liver regularly?
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Vitamin A
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What are the toxic / teratogenic effects of Vit A overload?
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- Dermatitis
- Hair Loss - Mucous Membrane Defects - Hepatic Dysfunction |
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What are the Sources of Vitamin E?
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- Vegetable Oils
- Canned / Frozen foods severely depleted - Naturally occuring antioxidant - Human milk a bad source |
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What is another name for D2?
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Ergocalciferol
- Widely found in plants / mould - Pharmaceutically / Food Additive as precursor ergesterol readily available - Prepared by action of UV light |
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What is another name for D3?
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Cholecalciferol
- Occurs naturally in anmals - Formed in skin by UV light - Acts like most steroid hormones eventually interacting with DNA |
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What is the function of VItamin D?
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Maintain correct levels of calcium and phosphate in the blood so that proper mineralisation of bone is achieved
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What are the toxic effects of Vit D?
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- Hypercalcaemia / GI tract disturbances / Calcification of soft tissues
- Intakes of 10 x RNI toxic |
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What are the main sources of Vitamin K?
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- Leafy Green
- Bacterial flora of Jejunum & Iliem |
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Which two vitamins is human milk low in?
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E & K
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What are the effects of a Vitamin K deficiency? When is it usually prevalent?
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- Defective blood clotting
- In long term antibiotic therapy |
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Why might infants have marginal Vitamin K deficiency?
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- Does not cross the placenta efficient
- Neonatal gut is sterile |
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RNI for Vit C in adults?
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~ 40mg
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In the fed state how does insulin affect FA synthesis?
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Insulin stimulates Acetyl CoA -> Fatty Acids
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What reaction does Acetyl CoA carboxylase catalyse?
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Acetyl CoA -> Malonyl CoA
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What effect does the presence of Malonyl CoA have?
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Inhibits carnitine transferase which inhibits FA entry into mitochondria and therefore oxidation
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Which co-enzyme is required for fatty acid and is provided by the hexose monophosphate shunt?
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NADPH
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Acetyl CoA + ...... = Malonyl CoA
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CO2
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What are the components of a TAG?
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- Glycerol Phosphate
- 3 Fatty Acids |
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What are the components of VLDL?
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- Apoproteins
- TAG - Phospholipids / Cholesterol |
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Are lipoproteins soluble in water? How are they transported?
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- insoluble in water
- Transported as lipid - protein complex |
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What is the function of apoproteins?
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- Structural role
- Recognised by receptors - Activate certain enzymes in lipid metabolism |
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What are Chylomicrons the main carrier of?
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Dietary TAG
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What are VLDL the main carrier of?
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Endogenous TAG
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What are LDL the main carrier of?
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Cholesterol to the tissues
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What are HDL the main carrier of?
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Cholesterol from tissues to liver
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How is exogenous fat transported from the Gut?
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- Nascent chylomicron containing apo B-48 & TAG from the intestine joins Apo E & C-II from HDL
- Lipoprotein Lipase in capillary hydrolyses to Chylomicron remnant / Glycerol / FA - FA travels to tissues becomes re esterified to TAG |
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What happens the Chylomicron remnant once it is formed in the capillary?
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- Contains Apo E so binds to Apo E receptor on liver
- Gets internalised & dismantled |
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How is exogenous fat transported from the Liver?
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- VLDL from liver (TAG + Apo B100) combines with HDL (Apo C-II & E) and enters capillaries
- Lipoprotein Lipase frees FA & splits VLDL to IDL (apo B-100 & TAG) & Glycerol |
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What is the fat of IDL produced from endogenous fat?
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- Half re-enters as HDL
- Half converts to LDL and travels to liver / peripheral tissue by B100 Receptors |
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What is the consequence of defective B-100 receptors?
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High Cholesterol
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What is the role of HDL in cholesterol transport?
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- Cholesterol from peripheral tissue esterified to cholesterol esters
- Need FA to esterify (taken from phosphatidylcholine on surface) to leave Lisophosphatidylcholine which activates LCAT (free cholesterol -> esters) |
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Which enzyme does LCAT catalyse?
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Free cholesterol -> Cholesterol Esters
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What si the action of CETP in cholesterol transport>
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Donates TAG to chylomicron & take CE then the remnants bind to SR-B1 receptors on the liver
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What is the action of HMG-CoA reductase?
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HMG-CoA ----> Mevalonate (((----> Cholesterol)))
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What is the effect of statins?
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inhibit HMG-CoA reeductase
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What sit eh effect of Cholesterol reaching the nucleus of a cell?
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Inhibits transcription of enzymes needed for cholesterol synthesis
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What is a trace element?
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An element in a sample that has an average concentration of less than 100 parts per million / 100 micrograms per gram
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What is SOD? In which enzyme category does it fall?
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- Superoxide Dismutase
- 2O2- --> O2 + O2 2- - Metalloenzyme |
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What class of molecules do trace elements have an important structural / functional role?
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Metallo Proteins / Enzymes
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What are the effects of a Zinc deficiency?
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- Severe skin lesions
- Hypergonadism - Slow Healing - Growth retardation - 10mg / day dietary intake |
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Why is Iron overload more common than others?
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There is no mechanism to remove excess from body
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What are the main functions of Iron in the body?
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- DNA synthesis
- Oxygen Transport - Oxidative energy production - Radical inactivity |
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What are the Iron requirements?
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- 1 mg infant / men / post menstrul
- 2 mg women - 3 mg pregnant |
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What is the function of Ferritin?
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- Soluble form of storage iron
- Taken up as Fe2+ and oxidised withing protein shell to Fe3+ - Mobilisation requires reduction to Fe2+ or proteloytic degradation |
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What is the function of Haemosiderin?
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- Water Insoluble
- Derived from ferritin - Found mainly in spleen / bone marrow / Kupfer cells in liver - Form iron deposited in overload |
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What is the function of Transferrin?
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- Transports FE from site absorption to utilisation
- Increases in iron deficiency - Usually only partly Fe saturated - Affinity reduced at acidic |
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What do LDL receptors recognise?
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B-100
- Remove LDL from the circulation (receptor mediated endocytosis) - Deficiency leads to hypercholesterolaemia |
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What is hypercholesterolaemia?
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High LDL
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What are the four genetic causes of Hyperlipoproteinemias?
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- Apoprotein deficiency
- High Chylomicrons & VLDL - C-II Deficiency - Defective LDL |
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What is Lipoprotein (a) and what is its significance?
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- LDL plus apoprotein a
- High plasma conc increased CHD risk - Related to plasminogen |
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What is the significance of lipoprotein a being related to plasminogen?
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Slows breakdown of blood clots by completing with plasminogen
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Why is lipoprotein a considered to be atherogenic?
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- Inhibts blood clot breakdown
- Interferes with platelet aggregation - Promotes generation of scavenger receptors - Leads to foam cell production - Damages vascular endothelium |
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Where in the blood vessel wall do LDL & Foam cells reside?
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Underneath the endothelial cells
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What effect does oxidation of LDL have on general cholesterol?
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Not recognised by the normal receptor but is taken up by scavenger receptors in foam cells. These receptors are not down regulated and the result is an accumulation of cholesterol
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How iron taken up by cells?
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- iron loaded transferrin binds to transferrin receptors on plasma membrane
- Receptor complexes migrate to clathrin-coated pits - Clathrin coated vesicles move from membrane and lose coat with reduced intra pH |
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What happens to the complex within the vesicle once it loses its clathrin coat?
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- Dissociation of iron from transferrn: transport of iron as Fe2+ via DMT1 into cytoplasm for storage / utilisation in mitochondria
- Vesicle returns to plasma membrane with receptor bound iron-free transferrin where iron-free transferrin dissociates from receptor |
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What is Ceruloplasmin?
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Enzyme Fe2+ --> Fe3+
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What is the change to skin colour by genetic haemochromatosis?
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- Ash-Grey Colour
- due to increased melanin production |
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What is the result of an accumulation of iron in the body past storable levels?
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- Ability of reticuloendothelial cells in spleen / bone marrow / lymph nodes to store iron is exceeded
- Release of iron to transferrin - Deposition at other sites particularly the heart - Cardiac failure . Damage to endocrine organs and liver |
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What is the mechanism behind chelation therapy?
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Treat patients with drugs that are able to bind iron
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What is IRP?
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Iron Regulatory Protein - Regulates synthesis of ferritin, transferrin receptor & other proteins
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Which protein is involved in the uptake of dietary heme by duodenal enterocytes?
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(HCP1)
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What is DMT1?
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Transports iron across apical membrane in intestines
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What is the action of heme oxygenase?
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Heme protein cleaved inside enterocyte to leave free Fe
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For what substance production is copper required?
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- Ferroxidase
- Cross linking of collagen / elastin - Catecholamine production - Melanin Production |
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What are the effects of a copper overload?
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- Yellow - Brown ring on cornea
- Build up in liver - Liver damage - Build up in brain - Mental Deterioration / Co-ordination loss - Chelation therapy is effective |
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Where is Adrenaline Produced?
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Adrenal Medulla
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Where is Cortisol Produced?
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Adrenal Cortex
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Where is Growth Hormone Produced?
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Anterior Pituitary
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What do Delta cells in plasma secrete?
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Somatostatin
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What three things stimulate insulin secretion?
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- Rise in blood glucose
- Rise in blood AA - Secretin & Other GI Hormones released after food intake before blood glucose elevated |
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What effect does adrenalin have on insulin?
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It inhibits insulin
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How does ionic movement control insulin release from beta cells?
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- Glucose reaches cell
- ATP closes K+ channels - Ca2+ channels open and Ca2+ moves in which promotes insulin release |
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What three things stimulate glucagon?
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- Low blood glucose
- High concentration of AA in the blood (prevents hypoglycaemia after protein meal) - Adrenaline |
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In periods of stress is insulin or glucago secretion stimulated?
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- Glucagon stimulated regardless of blood glucose
- Insulin suppressed |
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What are the metabolic effects of insulin?
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- Fuel storage post meal
- Promotes growth - Stimulates glycogen synthesis / storage - Stimulates fatty acid synthesis & storage when glycogen storage capacity exceeded - Stimulates AA uptake and protein synthesis |
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Insulin Receptor Structure?
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- Alpha subunit extracellular
- Beta subunit intracellular (IRS binding site) |
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How does insulin activate Akt protein kinase?
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- Insulin + Receptor phosphorylates IRS
- This activates P13 Kinase - This activates Pdk 1 - This activates Akt |
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What effect does insulin have on glucose transport?
|
- Akt phosphorylates and deactivates slycogne synthase kinase
- Cannot phosphorylate glycogen synthase so it remains active - Promotes glucose -> glycogen |
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What effect does active Akt have on GLUT transporters?
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- Translocates GLUT 4 to increase glucose uptake (muscle & adipose tissue)
- High concentrations lead to down regulation of receptors |
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What effect does insulin have on lipolysis?
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- Active Akt phosphorylates PDE so it is active
- PDE converts cAMP -> AMP - PKA inhibited - Hormone Senstive Lipase inhibited - TAG is not converted to glycerol & FA so is stored |
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How does insulin affect gene expression?
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- Insulin binding activates SHC which activates the Ras Pathway by way of GTP
- Raf phosphorylates MEK kinase which phosphorylates MAPK which stimulates transcriptional factor to bind to DNA & gene expression to occur |
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What are the metabolic effects of glucagon?
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- Mobilises fuel
- Activates Glycogenolysis & Gluconeogenesis - Activates AA uptake by liver for gluconeogenesis - Actiates FA release from adipose tissue - Activates FA oxidation & ketone body formation in the liver |
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What is the effect of adrenaline on the metabolism?
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Mobilises fuel during stress
- Stimulates glycogenolysis - Stimulates FA release from adipose |
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What is the effect of cortisol on the metabolism?
|
Long term requirements
- AA mobilisation from muscle - Stimulates gluconeogenesis - Stimulates FA release from adipose |
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What are the characteristics of the fed state?
|
- 2-4 hours after a meal
- Increase in blood glc, AA, TAG (chylo) - Synthesis/Storage of glycogen, TAG, protein |
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When is the liver engaged in gluconeogenesis?
|
All times except fed state (High Ins:GLu)
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Which enzyme when active stimulates glycolysis in the fed state?
|
Glucokinase
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Which two tissues rely on glucose as fuel?
|
- Brain - Blood Brain Barrier
- Erythrocyte - No Mito - GLUT 1 |
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Which two substances activate Hormone Sensitive Lipase?
|
Glucagon / Adrenaline
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At what concentration does the liver maintain blood glucose?
|
4mM
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Which three substances are used in gluconeogenesis?
|
Lactate / Glycerol / Amino Acids
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What process is the enzyme acetyl coA carboxylase involved with?
|
Acetyl CoA --> Fatty Acid
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Why is conversion to glucose over fatty acids favoured in the fasting state?
|
Liver Adipose tissue & Muscle can use FA as fuel
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What is ketone body formation?
|
- Acetyl CoA exceeds capacity of TCA cycle
- Channeled to ketone body formation - Acetoacetate and Bete hydroxybutyrate released into blood stream - Brain uses glc & some KB |
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What are the metabolic effects of ketone bodies?
|
- Stimulate insulin release
- Limits muscle proteolysis - Limits adipose lipolysis - muscle tissue conserved |
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What percentage of the population have diabetes?
|
2-3%
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KB produced in starvation stimulates insulin release which limits muscle protein breakdoen, release of FA from adipocytes and the uncontrolled production of KB
|
This mechanism does not exist in diabetes
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What BMI range is classed as clinical obesity?
|
BMI > 30
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Anaesthesia is more difficult & dangerous in the . . .
|
. . . obese
|
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Which cancers are more common in the obese?
|
Men - Colon / Rectum / Prostate
Women - Breast / Uterus / Cervix / Ovaries 9 year life expectancy reduction |
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How long can a previously fit young person live without food?
|
60 Days
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What percentage of the worlds population is undernourished?
|
~ 17%
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