Met Flashcards

1
Q

Formula for BMI

A

weight(kg)/height(m)^2

= BMI in kg/m^2

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2
Q

Give the BMI range for classification as clinically obese.

A

30-34.9 kg/m^2

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3
Q

Give the BMI range for classification as clinically underweight.

A

<18.5kg/m^2

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4
Q

Give the BMI range for classification as clinically normal.

A

18.5-24.9 kg/m^2

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5
Q

Give the BMI range for classification as clinically overweight.

A

25.0-29.9 kg/m^2

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6
Q

Describe the order fuel molecules are mobilised and utilised on an exended period of fasting.

A
Glucose from plasma
Glycogenolysis
Gluconeogenesis
FA and glycerol from AT
KB from FA via acetyl CoA
aa from muscle protein
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7
Q

Define homeostasis

A

the maintenance of the body’s internal environment within set limits, in a dynamic equilibrium.

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8
Q

Define and BMR and state factors which may affect it.

A

basal energy required to maintain life and so necessary for the functioning of various TOB at physical, digestive and emotional rest.

  • thyroid status
  • pregnancy/lactation
  • body weight
  • gender
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9
Q

Describe the effects of thyroid hormones T3 and T4.

A
  • Increase metabolic rate, catabolic effects generally, increase BMR: increase in size and no. of mit., increase O2 consumption and heat prod. and increase nutrient utilisation.
  • promote normal growth and devel.-increase synthesis of specific proteins. Directly affect bone mineralisation and increase synthesis of heart muscle protein.
  • CNS: hormones required for development of cellular processes of nerve cells, hyperplasia of cortical neurones and myelination of nerve fibres. Lack of T3 and T4 in adults characterised by poor conce., memory and lack of initiative.
  • Stimulate hormone and neurotransmitter receptor synthesis e.g. heart muscle, GI tract. Heart more sensitive to adrenaline and noradrenaline. Increased motility in GI tract.
  • Allow actions of FSH and LH. Necessary for ovulation.
  • Increase turnover of proteins and glycoproteins in skin and subcutaneous tissue.
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10
Q

Describe lactose intolerance

A

Low lactase activity necessary to digest lactose to glucose and galactose. Lactose not absorbed is fermented by gut bacteria, producing lactic acid, methane gas and hydrogen. Water potential of gut lumen is lowered so fluid and electrolytes are secreted, causing diarrhoea. Gases cause stomach cramps, and flatulence and nausea may also be experienced. Condition may also affect galactose met.

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11
Q

How are thyroid hormones transported in the bloodstream?

A

Thyronine binding globulin, also pre-albumin and albumin. T4 binds with a greater affinity and so has a longer 1/2 life.

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12
Q

What is the mechanism of action of thyroid hormones?

A

T3 and T4=hydrophobic, so cross PM of cells, and interact with specific receptors in nucleus and possibly mit. Binding to hormone-binding domain of receptor induces a conformational change in receptor, unmasking the DNA binding domain. Interaction of hormone-receptor complex with DNA increases rate of transciption of specific genes translated into proteins. Increased rate of protein synthesis stimulates oxidative energy met. in target cells to provide extra energy required for protein synthesis- this also produces increased amounts of functional proteins so increased cell activity.

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13
Q

What treatment can be given for alcoholism and how does it work?

A

Disulfiram- inhibits the aldehyde dehydrogenase enzyme in alcohol metabolism, so toxic acetaldehyde accumulates, causing hangover symtpoms e.g. nausea for a week.

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14
Q

Anatomical location of the thyroid gland

A

base of neck, anterior to lower larynx and upper trachea

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15
Q

Describe thyroid hormone synthesis

A

ATE ICE

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16
Q

Why does a patient with hyperthyroidism suffer heat intolerance?

A

Excess thyroid hormones in bloodstream increase metabolic rate, so increased respiration in cells, and energy produces is dissipated as heat, so core temp. rises.

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17
Q

What test can be used to diagnose Cushings disease from cushings syndrome

A

High dose Dexamethasone suppression test

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18
Q

Describe the Dexamethasone suppression test

A

Dexamethasone=potent synthetic steroid which when given orally, normally suppresses secretion of ACTH and thus cortisol by feedback inhibiton. Suppression of plasma cortisol by >50% is characteristic of Cushing’s disease, as though diseased pituitary is relatively insensitive to cortisol, it is still sensitive to potent synthetic steroids. Suppression does not normally occur with adrenal tumours or ectopic ACTH secretion.

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19
Q

How can synacthen be used to test adrenocorticol functin?

A

Synacthen=ACTH analogue, given intramuscularly, which would normally increase plasma cortisol by >200nmol/l. A normal response usually excludes Addison’s disease.

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20
Q

Why can a person with Addison’s disease suffer from increased skin pigmentation?

A

Lack of cortisol- stimulates release of ACTH from the anterior pituitary via -ve feedback. The MSH sequence is contained with the primary sequence of ACTH so when ACTH is present at high levels, it can exert similar effects to MSH, stimulating melanocytes to produce and secrete melanin, so increased secretion of melanin by melanocytes in the skin which gives skin its pigmentation.

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21
Q

Where is glucokinase found and why does it have a high Km?

A

Liver
High Km=low affinity, so glucokinase only converts glucose to G6-P when glucose is at very high concentrations which is important as G6-P formed in the liver will be converted to glycogen for storage, and so we only want this when glucose is in excess.

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22
Q

List 2 functions of glucose 6P-dehydrogenase.

A
  • NADPH production

- production of ribose sugars for nucleotide synthesis.

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23
Q

Describe the use of carbimazole in treating hyperthyroidism.

A

Carbimazole prevents the iodination of thyroglobulin when forming thyroid hormones, by inhibiting the thyroid peroxidase enzyme.

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24
Q

Why would a patient with G-6P dehydrogenase deficiency present with jaundice?

A

Enzyme catalyses Pentose Phosphate pathway respnsobile for NADPH prod. So reduced NADPH, meaning increased disulphide bond formation between adjacent Cys residues on aa in Hb bolecule, forming Heinz bodies. Therefore, increased rbc lysis, producing lots of bilirubin, unable to all be conjugated by liver fast enough so remains in bloodstream, causing jaundice.

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25
Q

What is released from delta cells of pancreas and what does this do?

A

Somatostatin, inhibits GH release from anterior pit.
Also released from delta cells of stomach, and inhibits gastric acid production via its action on both parietal cells and G cells to inhibit gastrin secretion and HCL production.

26
Q

Rate limiting enzymes of glycolysis?

A

Hexokinase
Phosphofructokinase
Pyruvate kinase

27
Q

What is a heinz body and give an example of a condition in which they are formed?

A

Heinz bodies are aggregates of denatured and precipitated Hb within rbc, which result in a shorter life span of rbc, which are more likely to get trapped in small blood vessels as the heinz body alters the ability of the rbc to change its shape in order to pass through narrow blood capillaries.
G6PDHD: deficiency of enzyme catalysing the PPP responsible for NADPH prod., so lack of NADPH necessary for maintaining free SH groups on adjacent cysteine residues. In absence, S-S bond form between the adjacent cysteine residues on proteins, forming insoluble aggregates of Hb- heinz bodies.

28
Q

Describe the control system of the the hypothalamic-pituitary-adrenal axis

A

System uses -ve feedback. CRH (corticotropin releasing hormone) released from hypothalamus into local portal circulation and binds to specific receptors on corticotroph cells of anterior pituitary, stimulating ACTH release, which travels in the blood to cortex of adrenal gland where binds to receptors on cells in zona fasciculata, stimulating cortisol releases into circulation- stress hormone. ACTH inhibits CRH release, and cortisol inhibits CRH and ACTH release. Axis is activated as part of body’s normal response to stress and levels of ACTH and cortisol in blood correspond to stress levels.

29
Q

How is cortisol transported in blood?

A

Bound to transcortin as steroid hormone- lipophilic. ~10% free and active

30
Q

Ratio of T3 to T4 production?

A

1:10

31
Q

why can’t acetyl coA be used in gluconeogenesis?

A

reaction catalysed by pyruvate dehydrogenase irreversible

32
Q

how does homocystinuria cause CT disorders?

A

accumulation of homocysteine and methionine which interfere with cross linking of collagen fibres

33
Q

example of a prodrug given, then activated by body in phase I drug metabolism?

A

codeine

converted to morphine- analgesic, given post MI- MONA, and causes respiratory depression

34
Q

cofactor for phase 1 drug metabolism?

A

NADPH

35
Q

drug that bypasses phase 1 metabolism as reactive group already exposed?

A

morphine

36
Q

3 examples of conjugates in phase II drug met

A

glucuronic acid
glutathione- paracetemol OD
sulphate ions

37
Q

high energy cofactor for phase II drug metabolism?

A

uridine diphosphate glucuronic acid

38
Q

function of N-acetyl cysteine in paracetemol OD?

A

acts as an anti-oxidant as can be oxidised by ROS

39
Q

where does insulin act to result in the uptake of glucose from the bloodstream?

A

liver, muscle and adipose tissue

40
Q

how is hormone secretion controlled in the body?

A

-ve feedback
secretion of 1 hormone controlled by another
releasing and inhibiting hormones e.g. somatostatin
inactivation of hormones by liver and kidneys e.g. steroid hormones made water soluble so can be excreted in urine or bile

41
Q

describe the production of insulin

A

synthesised as preproinsulin in ribosomes associated with the ER, signal peptide attached to N-terminal sequenced- cleaved in ER lumen by a signal peptidase, to form proinsulin. Specific folding occurs with the formation of disulphide bonds. Endopeptidases then cleave C peptide as recognise basic aa pairs so mature insulin formed. Insulin and C peptide in equimolar amounts in secretory granules so released in quimolar amounts, hence C -peptide is a good marker for measuring endogenous insulin levels

42
Q

define diabetes

A

a group of metabolic disorders characterised by chronic hyperglycaemia, and insulin deficiency, resistance or both

43
Q

why is insulin given subcutaneously?

A

polypeptide hormone so if given orally, would be broken down by pepsin in the stomach

44
Q

how does metformin act in treating diabetes?

A

inhibits gluconeogenesis which is main process producing chronic hyperglycaemia as low insulin to anti insulin ratio activates the rate limiting enzymes of gluconeogenesis: PEPCK and fructose-1,6-bisphosphatase

45
Q

how is a response coordinated by secondary neurones in control of appetite?

A

via vagus nerve

46
Q

what is POMC- a polypeptide prohormone released from primary inhibitory neurones, cleaved to produce?

A

ACTH
beta endorphin
alpha-melanocyte stimulating hormone- acts on melanocortin 4 receptors to suppress appetite

47
Q

define metabolic syndrome

A

group of symptoms including insulin resistance, glucose intolerance, hypertension and dyslipidaemia, assoc with central adiposity. co-occurrence of a number of CVS RFs such as dyslipiudaemia and hypertension, usually in assoc with overweight or obesity and sedentary lifestyle, is the metabolic syndrome

48
Q

how does ACTH stimulate production of steroid hormones?

A

hydrophilic so binds to cell surface receptors in zona fasciculata and reticularis, causing activation of cholesterol esterase which increases the conversion of cholesterol esters to free cholesterol for steroid hormone synthesis

49
Q

tment of an addisonian crisis?

A

IV cortisol

fluid replacement- dextrose in normal saline

50
Q

how does covalent modification affect phosphofructokinase?

A

high insulin to anti insulin ratio, dephosphorlylation?- activates PFK, so promotes glycolysis

51
Q

define hypoglycaemia and list its clinical signs

A

plasma glucose concentration of less than or equal to 3mmol/L
similar signs to someone intoxicated with alcohol
include slurring of speech, confusion, drowsiness, weakness, trembling, sweating, nausea, tingling around lips, palpitations, staggering walk.

52
Q

what endocrine blood tests would be conducted to determine an endocrine basis for fasting hypoglycaemia?

A

insulin
GH
glucagon
cortisol

53
Q

what advice would you give to a patient who suffers from fasting hypoglycaemia e.g. due to enzyme defect in gluconeogenesis pathway?

A

to avoid fasting!

54
Q

enzymes required for glycogen mobilisation from liver?

A

glycogen phosphorylase
phosphoglucomutase
glucose 6-phosphatase

55
Q

During stress, what hormones inhibit insulin release from beta cells of pancreas?

A

the catecholamines adrenaline and noradrenaline so blood glucose remains high

56
Q

why must diabetic ketoacidosis be treated rapidly?

A

death may rapidly occur due to electrolyte imbalance causing a loss of enzyme functioning

57
Q

list signs/symptoms experienced by a type 1 diabetic on first presentation?

A
polyuria
polydipsia
weight loss
weakness/tiredness
glycosuria
nausea/vomiting if ketoacidosis
58
Q

give 3 reasons as to why hyperglycaemia occurs in untreated type 1 diabetes?

A

reduced uptake of glucose from blood by skeletal muscle and AT
reduced storage of glucose as glycogen in liver and SM, and increased glycogenolysis
increased production of glucose by liver via gluconeogenesis

59
Q

list signs and symptoms of cushing’s syndrome

A
central adiposity
moon-shaped face
purple striae on lower abdomenn, upper arms and thighs
thin arms and legs
muscle weakness
high BP
polyuria and polydipsia
increased susceptibility to infections and acne
back pain and rib collapse
60
Q

why might a patient with cushing’s disease present with back pain?

A

osteoporosis of the vertebrae may predispose to fractures, as a result of high cortisol disrupting calcium metabolism and causing loss of bone matrix protein