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Randoms Flashcards

1
Q

What condition uses the drug carbimazole for treatment?

A

treat hyperthyroidism
pro-drug and is converted to its active form methimazole by the body.
methimazole prevents the enzyme thyroid peroxidase from coupling and iodinating tyrosine residues on thyroglobulin therefore reducing the production of thyroid hormones T3 and T4

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2
Q

can ROS damage proteins and result in protein glycosylation?

A

no-

glycosylation is a normal post- translational modification

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3
Q

What is the term that describes abnormally shaped RBCs?

A

Poikilocytosis

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4
Q

Glycerol released upon the hydrolysis of triacylglyercol can enter which pathway after additional reactions?

A

glycolysis -

after phosphorylation to glycerol phosphate and concession to dihydroxyacetone phosphate, glycerol can enter glycolysis.

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5
Q

in which nucleus of the hypothalamus are the neurones that constitute as the biological clock located?

A

suprachiasmatic nucleus

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6
Q

what are two endogenous sources of free radicals?

A
  • ETC major source
  • peroxidase enzymes
  • nitric oxide synthase
  • NADPH oxidase enzyme
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7
Q

What is the correct sequence of lipoproteins in the order of most to least dense?

A

HDL> LDL> VLDL> chylomicrons

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8
Q

What is the mode of action of spironolactone?

A

mineralocorticoid receptor antagonist

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9
Q

what is the role of leutinizing hormone in men?

A

LH acts upon Leydig cells of the testis to control the production of testosterone

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10
Q

what does the membrane bound enzyme thyroid peroxidase regulate?

A
  • oxidation of iodide to iodine
  • addition of iodine to tyrosine acceptor residues on thyroglobulin
  • coupling of monoiodotyrosine and diiodotyrosine molecules within thyroglobulin
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11
Q

the cause of pernicious anaemia?

A

auto-antibodies interfering with the production or function of intrinsic factor
intrinsic factor essential for the absorption of bit B12 in the ileum.

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12
Q

name a carbohydrate that is a source of dietary fibre

A

cellulose

- others include lignin, pectin and gums

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13
Q

What is the primary abnormality in patients presenting with diabetic ketoacidosis

A

absolute insulin deficiency leading to ketone production

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14
Q

which endocrine gland secretes melatonin (hormone)?

A

Pineal glands

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15
Q

What effect would a decrease in intracellular ATP conc have on the ATP sensitive K+ channels in pancreatic beta cells?

A

more K(ATP) channels would be in the open state

  • these channels are inhibited by ATP
  • fall in ATP will leave more channels open
  • more K+ ions leave the cell through the channel so plasma membrane becomes hyperpolarised
  • more - membrane potential makes cells less excitable
  • prevent insulin release
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16
Q

What is a treatment option for a patient with severe hereditary haemochromatosis

A

therapeutic phlebotomy to remove excess iron

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17
Q

what is Hereditary haemochromatosis

A

autosomal recessive disorder of iron metabolism that results in toxic levels of iron accumulation
excess iron affect organ function by direct toxic effects

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18
Q

which class of hormone does adrenaline fall under?

A

amine hormone

- synthesised from the amino acid tyrosine

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19
Q

which disease results from excess growth hormone secretion occurring after puberty after the epiphyseal plates have closed?

A

Acromegaly

- anterior pituitary glad produces excess growth hormone after epiphyseal plate closure at puberty

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20
Q

activation of which adrenergic receptor subtype mediates the effect of adrenaline and noradrenaline on the heart?

A

Beeta-1 adrenergic receptor

- through Gapha-s

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21
Q

what is a symptom of hypocalcaemia

A

tetany

- muscle spasms

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22
Q

what is the half life of thyroxine (T4) in plasma?

A

around 5-7 days

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23
Q

what is the half life of T3?

A

around 1 day

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24
Q

activation of which adrenergic receptor subtype mediates bronchodilator in the lungs?

A

Beta-2 adrenergic receptor

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25
Q

which breakdown product of haem is responsible for the yellow discolouration often seen around a bruise?

A

bilirubin

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26
Q

which type of diabetes shows markers for autoimmunity

A

type I diabetes mellitus

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27
Q

which hormone is released from the pancreas and supresses appetite?

A

amylin

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28
Q

what inhibits the release of iron from erythrocytes and macrophages?

A

hepcidin

  • inhibits iron transport by binding to ferroportin located on the basolateral membrane of erythrocytes.
  • inhibition of ferroportin by hepcidin prevents iron from being exported into the bloodstream thereby reducing dietary iron absorption
  • iron release from macrophages is also reduced by hepcidin inhibition of ferroportin
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29
Q

A child has ‘glycogen storage disease type 1). his abdomen is large and potuberant. why is his abdomen protuberant?

A

liver is enlarged due to glycogen accumulation

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30
Q

what is the desirable range for BMI?

A

18.5-24.9 kg/m2

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31
Q

what could be a treatment option for a patient with beta Thalassaemia?

A

red cell transfusion
- iron overload is a major cause of premature death in thalassaemias duet excessive absorption of dietary iron due to ineffective haematooiesis and the repeated blood transfusions required to treat the anaemia

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32
Q

when does the switch from fetal to adult haemoglobin occur?

A

around 3-6 months of age

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33
Q

what is measured by a direct Coombs test?

A

antibodies bound directly to the surface of RBCs

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34
Q

when is a direct Coombs test used?

A
  • when immune- mediated haemolytic anaemia is suspected

- test determines if antibodies or complement system factors have bound to RBCs surface antigens in vivo

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35
Q

What do the parafollicular cells within the thyroid gland secrete?

A

calcitonin

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36
Q

where is thyroid hormone synthesised?

A

synthesised in and released from the thyroid follicles

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37
Q

What are follicular cells filled with?

A

colloid

- deposit of the protein thyroglobulin

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38
Q

What is present in a patient with Felty’s syndrome?

A

RhA, splenomegaly, neutropenia

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39
Q

what produces the glycoprotein hormone erythropoietin?

A

interstitial fibroblasts in the kidney

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40
Q

what is a feature of anabolic pathways?

A

they involve the synthesis of larger molecules from intermediary metabolites

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41
Q

where is thyroid stimulating hormone released from?

A

anterior pituitary gland

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42
Q

what are the examples of a ketone body?

A
  • acetone
  • acetoacetate
  • beta- hydroxybutyrate
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43
Q

what are the two most significant factors underlying the aetiology of metabolic syndrome

A
  • insulin resistance

- central obesity

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44
Q

what are some features of hypothyroidism?

A
  • weight gain
  • myxoedematous facies
  • menorrhagia
  • hair loss
  • constipation
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45
Q

which hormone is responsible for the short term regulation of serum calcium?

A 
parathyroid hormone (PTH) and the active form of Fit D (calcitrol) both raise serum calcium concentrations
short term regulation of serum calcium is under the control of PTH, whereas calcitriol is responsible for longer term regulation
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46
Q

what is the glucagon receptor type?

A

GPCR

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47
Q

what are Kupffer cells?

A
  • type of macrophage
  • part of the reticuloendothelial system
  • found in the liver
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48
Q

which disease is caused by an aldosterone secreting adrenal adenoma?

A

Conn’s disease

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49
Q

what is the effect of increased parathyroid hormone secretion on plasma phosphate level?

A

decreased plasma phosphate

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50
Q

what does parathyroid hormone secretion do?

A
  • stimulates osteoclast activity in bone resulting in the release of both calcium and phosphate.
  • also stimulates the kidney to increase the reabsorption of calcium and decrease the reabsorption of phosphate
  • more phosphates lost in the urine than gained from bone mineralisation- the net effect is to increase plasma calcium and decrease plasma phosphate
  • also has indirect effects on the GI tract by promoting the formation of calcitriol (active form of Vit D)
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51
Q

which enzyme protects cells from oxidative damage by converting H2O2 to water and oxygen?

A

catalase

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52
Q

in which organ does cleavage of angiotensin I into angiotensin II mainly occur?

A

mainly converted using ACE within the lung capillaries

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53
Q

name the glycated form of haemoglobin that is measured as an indicator of average plasma glucose conc over a prolonged period of time

A

HbA1c

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54
Q

why might a patient with a pituitary adenoma develop visual field loss?

A

growth of the adenoma can cause physical compression of the optic chiasm

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55
Q

After receiving an injection of insulin, what would you expect to happen to the plasma C- peptide conc in a type 1 diabetic?

A

C- peptide conc would remain the same

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56
Q

what type of receptor does thyroid hormone bind to?

A

nuclear receptor

  • hormone activated transcription factors to modulate gene expression
  • thyroid hormone receptors can bind DNA in the absence of hormone, usually leading to transcriptional repression
  • hormone binding is associated with a conformation change in the receptor that causes it to function as a transcriptional activator rather than a repressor
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57
Q

what happens to the serum TSH level in hyperthyroidism?

A

decreases below the normal range

- due to negative feedback on the hypothalamus and anterior pituitary from thyroid gland

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58
Q

what type of hormone is cortisol?

A

steroid hormone synthesised from cholesterol

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59
Q

Squamous tumours of the lung, head and neck can sometimes produce a hormone that can cause hypercalcaemia. what is this hormone

A

Parathyroid hormone- related peptide (PTHrp)

- acts at parathyroid hormone receptors

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60
Q

what is allosteric regulation?

A

the regulation of a protein by the binding of an effector molecule at a site other than the protein’s active site

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61
Q

which hormone released by the hypothalamus inhibits the release of grow hormone from the anterior pituitary gland?

A

Somatostatin

- also known as Growth hormone inhibiting hormone (GHIH)

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62
Q

which NT is released from primary neurones in the arcute nucleus of the hypothalamus to suppress appetite?

A

alphaMSH and beta-endorphin

effect on secondary neurones results in inhibition of hunger (promotion of satiety)

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63
Q

which cell type facilitates the recycling of iron from old RBCs?

A

macrophages

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64
Q

what effect would an increased conc of ADH have on the reabsorption of water from urine into blood in the collecting ducts of the kidney?

A

promotes reabsorption of water

results in a smaller volume of more concentrated urine

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65
Q

how would you expect the aldosterone: renin ratio to be like in a patient with secondary hyperaldoesteronism caused by renal artery stenosis?

A

low

secondary: low ratio
primary: high ratio

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66
Q

what is Band 3.1?

A

component of the red cell membrane cytoskeletal network

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67
Q

during periods of starvation, which organs contribute to gluconeogenesis?

A

liver and kidney

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68
Q

Where is the hormone oxytocin synthesised?

A

hypothalamus

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69
Q

which drug is administered for a paracetamol overdose?

A

acetylcysteine

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70
Q

in which nucleus of the hypothalamus are the neurones that synthesise ADH located?

A

paraventricular nucleus

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71
Q

which type of cell in the islets of Langerhans produce insulin?

A

beta cells

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72
Q

which type of cell in the islets of Langerhans produce glucagon?

A

alpha cells

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73
Q

what would be two signs that would be indicative of Graves’ disease over other types of hyperthyroidism?

A

exopthalmos and Pre- tibial myxoedema

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74
Q

name a hormone produced by the placenta that exerts an anti-insulin effect on maternal metabolism

A

Corticotropin releasing hormone
- stimulates the release of corticotropin

human placental lactose and progesterone - do not know mechanisms

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75
Q

what effect would insulin have on the enzyme glycogen synthase in the liver?

A

increase in activity

- glycogen synthase is the rate limiting enzyme in glycogen synthesis

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76
Q

the parafollicular cells within the thyroid gland secrete which substance?

A

calcitonin

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77
Q

what is an effect of thyroid hormone?

A

increase in the size of mitochondria

- thyroid hormone stimulates an increase in both the number and size of mitochondria in cells

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78
Q

what is the mode of action of hydroxycarbamide in treating polycythaemia vera?

A

inhibits DNA synthesis

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79
Q

what is a polymer of glucose?

A

cellulose, starch and glycogen

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80
Q

is NADH considered a high or low energy signal in the cell?

A

high

when levels of NADH are high in the ETC can produce ATP in abundance

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81
Q

which glucose transporter is regulated by insulin?

A

GLUT4
expressed by skeletal muscle and adipose tissue
responsible for insulin- regulated glucose uptake

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82
Q

thyroid hormone secreted from the thyroid gland is mostly in which form?

A

T4

most is converted to T3 in the liver and kidneys

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83
Q

in which nucleus of the hypothalamus are the neurones that constitute the biological clock located?

A

Suprachiasmatic nucleus

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84
Q

in which nucleus of the hypothalamus are the neurones that regulate appetite located?

A

Arcuate nucleus

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85
Q

which endocrine gland secretes the hormone melatonin?

A

the pineal gland

- melatonin is a hormone involved in setting the biological clock

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86
Q

what would be the expected total volume of blood in a 70kg man?

A

around 5L of blood

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87
Q

do the units mOsmol/L refer to the osmolality or osmolarity of the solution?

A

osmolarity

- refers to number of osmoles per L of solution

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88
Q

A solution of normal saline has a conc of 308 mOsmol/L (9.0g per L). what conc of Na+ ions would be in this solution?

A

154 mM (mmol/L)

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89
Q

what term is used to describe low blood sodium?

A

hyponatraemia

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90
Q

what effect would an increased conc of ADH have on the reabsorption of water?

A

promote reabsorption of water

smaller volume of more conc urine produced

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91
Q

in which region of the brain are the osmoreceptors located?

A

hypothalamus

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92
Q

define hormone

A

chemical signals produced in endocrine glands or tissue that travel in the bloodstream to cause an effect on other tissues

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93
Q

define paracrine

A

mode of signalling in which a hormone acts over a short distance via interstitial fluid to affect a response in an adjacent/ nearby cell

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94
Q

which class of hormone does cortisol fall under?

A

steroid hormone

as it is derived from cholesterol

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95
Q

which class of hormone does adrenaline fall under?

A

amine hormone

synthesised from the AA tyrosine

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96
Q

which class of hormone does thyroid hormone fall under

A

amine hormone

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97
Q

are thyroid hormones water or lipid soluble?

A

lipid soluble

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98
Q

what is the precursor molecule used to synthesise steroid hormones?

A

cholesterol

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99
Q

where is ADH synthesised?

A

hypothalamus

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100
Q

which hormone is released from the stomach when it is empty in order to stimulate appetite?

A

Ghrelin

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101
Q

which hormone is released from adipocytes and suppresses appetite?

A

leptin

102
Q

which Its are released from primary neurones in the arcuate nucleus of the hypothalamus to stimulate appetite?

A

Neuropeptide Y (NPY) and agouti-related peptide (AgRP)

103
Q

name the peptide precursor of the NTs alpha- MSH, beta-endorphin and ACTH (adrenocorticotropic hormone?

A

POMC

104
Q

what is the name given to the regions of the pancreas that contain endocrine cells ?

A

islets of Langerhans

105
Q

which type of cell in the islets of Langerhans produce insulin?

A

beta cells

106
Q

what is the term used to describe the excretion of glucose in urine?

A

Glucosuria

above the renal threshold for glucose (around 10 mmol/L)

107
Q

what is the half-life of insulin in plasma?

A

5 minutes

108
Q

how many disulphide bonds are present in insulin?

A

3

109
Q

what is the C-peptide of insulin?

A

connects the A and B chains of proinsulin

used as a clinical marker for endogenous insulin release (longer half life and so is more stable than insulin in plasma)

110
Q

which glucose transporter is the primary transporter of glucose in pancreatic beta cells?

A

GLUT2
also the major transporter in liver
bidirectional transporter, allowing glucose to flow in both directions
GLUT2 allows hepatocytes to export glucose made by gluconeogenesis into the blood
GLUT2 is not regulated by insulin

111
Q

with respect to the release of insulin, what effect would an increase in the intracellular conc of ATP have on a pancreatic beta cell?

A

insulin secretion would increase

  • how beta cells sense an increase in plasma glucose
  • more ATP produced from the metabolism of glucose results in inhibition of the ATP- sensitive K channels
  • less (+) charged K leaving the cell through KATP channels results in depolarisation of the plasma membrane
  • depolarisation is sensed by voltage activated calcium channels which open allowing calcium to flow down its electrochemical gradient into the cell
  • this influx of calcium ions into the beta cell that activates the insulin containing vesicles causing them to fuse with the plasma membrane and release insulin
112
Q

what type of hormone is insulin?

A

peptide hormone

113
Q

is insulin a water or lipid soluble hormone?

A

water soluble

114
Q

which class of receptor is the insulin receptor?

A

tyrosine kinase superfamily of receptors

115
Q

which type of cell in the islets of Langerhans produce the hormone glucagon?

A

alpha cells

116
Q

what is the term used to describe excessive thirst?

A

polydipsia

117
Q

which type of diabetes shows markers for autoimmunity?

A

Type I

  • Islet cell autoantibodies (ICAs) and insulin autoantibodies (IAA)
  • can be detected several months/ years before onset of the disease
118
Q

what is the classic triad of symptoms for Type I DM

A
  • polyuria
  • polydipsia
  • weight loss (protein and fat metabolised due to absence of insulin)
119
Q

what would happen to the pH of blood if excessive amount of ketone bodies were synthesised and released by the liver of a patient with type I diabetes?

A

pH would fall

  • large amounts of ketone bodies produced
  • H+ association with ketone produce a metabolic acidosis
120
Q

what Is the normal range for plasma glucose?

A

3.3- 6.0 mmol/L

121
Q

why is insulin injected and not taken orally?

A

peptide hormone

broken down in GI tract to its constituent AA

122
Q

What is the mode of action of Metformin? (for Type 2 diabetics)

A

inhibit hepatic gluconeogenesis

- acts to lower plasma glucose

123
Q

name the glycated form of haemoglobin that is measured as an indicator of average plasma glucose conc over a prolonged period of time

A

HbA1c

124
Q

is the glycation of haemoglobin to form HbA1c catalysed by an enzyme?

A

no

- non-enzymatic random process that disrupts protein structure and function

125
Q

in which nucleus of the hypothalamus are the neurones that synthesise oxytocin located?

A

paraventricular nucleus and supraoptic nuclei

126
Q

in which nucleus of the hypothalamus are the neurone that synthesise ADH (vasopressin) located?

A

supraoptic and paraventricular nuclei

127
Q

list 6 hormones produced by the anterior pituitary gland

A 
TSH thyroid stimulating hormone 
ACTH Adrenocorticotropic hormone
LH luteinising hormone
FSH follicle stimulating hormone
PRL prolactin 
GH Growth hormone
128
Q

describe the embryological origin of the anterior lobe of the pituitary gland

A

up-growth of ectodermal cells from the roof of the primitive pharynx

129
Q

list the hormones released from the posterior pituitary gland

A

oxytocin

ADH

130
Q

which organ releases IGF-1 into blood in response to growth hormone stimulation?

A

liver

131
Q

which hormone released by the hypothalamus inhibits the release of growth hormone from the anterior pituitary gland?

A

GHIH (growth hormone inhibiting hormone)- also known as somatostatin

132
Q

when does acromegaly occur

A

excess growth hormone secretion occurring after puberty after the epiphyseal plates have closed

133
Q

what kind of receptor is the Growth hormone receptor?

A

tyrosine kinase receptor

134
Q

why might a patient with a pituitary adenoma develop visual field loss?

A

growth of adenoma can cause physical compression of the optic chiasm

135
Q

what is a symptom of hyperprolactinaemia in women

A

galactorrhoea= milky secretions from the breast

refers to the milk secretion not due to breast feeding

136
Q

what would be a biochemical finding in a patient with acromegaly

A

plasma IGF-1 above the normal range

excessive growth hormone would stimulate IGF production by the liver and muscle - therefore an increased IGF-1 in plasma

137
Q

what is neurogenic diabetes insipidus?

A

lack of vasopressin (ADH) production in the brain. Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced.

138
Q

define pituitary apoplexy

A

sudden vascular event (bleeding into or impaired blood supply) in a pituitary tumour
patients may show sudden set headache, double vision, cranial nerve palsy, visual field loss and hypopituitarism

139
Q

what is a typical clinical consequence of untreated central (neurogenic) diabetes insipidus

A

hypernatraemic dehydration

patient does not drink adequately

140
Q

what Is the normal pattern of plasma cortisol conc

A

peak in the morning

gradually declines throughout the day to the lowest levels around midnight before increasing again during the night

141
Q

what is the role of leutinizing hormone in men?

A

control production of testosterone by the testis

142
Q

what is transsphenoidal surgery

A

removal of pituitary tumour by inserting an endoscope and /or surgical instruments through the nose

143
Q

which type of drug can be used to treat prolactinoma

A

dopamine receptor agonist
dopamine inhibits prolactin release
therefore stimulation of dopamine receptors would inhibit the release of prolactin

144
Q

what structure joins the two lobes of the thyroid gland?

A

isthmus

145
Q

the parafollicular cells within the thyroid gland secrete which substance?

A

calcitonin

- located in the spaces between thyroid follicles

146
Q

how many iodine molecules does thyroxine have?

A

4

147
Q

what does the membrane bound enzyme thyroid peroxidase regulate?

A
  • oxidation of iodide to iodine
  • addition of iodine to tyrosine acceptor residues on thyroglobulin
  • coupling of monoiodotyrosine and diiodotyrosine molecules within thyroglobulin
148
Q

thyroid hormone secreted from the thyroid gland is mostly in which form?

A

T4

- converted to T3 in the liver and kidneys

149
Q

where is thyroid stimulating hormone released from?

A

anterior pituitary gland

150
Q

what type of receptor does thyroid hormone bind to?

A

nuclear receptor

  • hormone activated transcription factors to modulate gene expression
  • in the absence of hormone, thyroid hormone receptors can bind DNA, usually leading to transcriptional repression
151
Q

which thyroid hormone has the longest half life?

A

T4

152
Q

what protein serves to transport thyroid hormone in plasma?

A

thyroxine- binding globulin (TBG)

153
Q

which condition can be treated by the drug carbimazole?

A

hyperthyroidism

  • pro drug which is converted to its active form methiazole in the body
  • prevents thyroid peroxidase from coupling and iodinating tyrosine residues on thyroglobulin
  • therefore reduces the production of thyroid hormones T3 and T4
154
Q

Define cretinism

A

hypothyroidism in a neonate

results in dwarfed stature, severe mental retardation, poor bone development, muscle weakness and GI disturbances

155
Q

what type of hormone is thyroid stimulating hormone

A

glycoprotein

- consisting of two subunits- alpha and beta

156
Q

what would be seen with dietary iodine deficiency

A

low T3, T4
high TSH from anterior pituitary gland
dietary iodine deficiency always results in goitre

157
Q

Describe Graves’ diease

A

autoimmune disease resulting from the production of thyroid stimulating immunoglobulins (TSI)
stimulate T3, T4 release, TSH secretion decreases due tp (-) feedback
TSI outside normal (-) feedback pathway
usually present with goitre

158
Q

which drug is commonly associated with the side effects that disrupt thyroid function

A

amiodarone

- structurally smiler to thyroxine and so can disrupt thyroid function

159
Q

why does the thyroid gland move up on swallowing

A

invested by the pre-tracheal fascia

160
Q

how to describe a thyroglossal cyst

A

in midline and moves up on tongue protrusion

161
Q

what type of hormone is parathyroid hormone?

A

peptide hormone

162
Q

what are the actions of parathyroid hormone on the GI tract?

A

indirect action via promoting the formation of calcitriol (active form of Vit D)

163
Q

what is the cell type responsible for the breakdown of bone matrix to release calcium and phosphate into the blood?

A

osteoclasts

164
Q

where is calcitonin produced?

A

in the parafollicular cells of the thyroid gland

165
Q

what type of hormone is calcitonin?

A

peptide hormone

166
Q

What converts 7-dehydrocholesterol into Vit D3?

A

sunlight

167
Q

What is the action of calcitonin on the GI tract?

A

has no effect

calcitrol acts to increase the absorption of both calcium and phosphate in the GI tract

168
Q

what are the principle cells of the parathyroid gland also called?

A

chief cells

these secrete parathyroid hormone

169
Q

how does the parathyroid gland sense plasma calcium conc?

A

by GPCRs that are activated by Calcium

170
Q

what is the effect of increased parathyroid hormone secretion on plasma phosphate level?

A

decreased plasma phosphate

  • parathyroid hormone stimulates osteoclast activity in bone resulting in the release of both calcium and phosphate
  • parathyroid hormone also stimulates the kidney to increase the reabsorption of calcium and decrease the reabsorption of phosphate
  • more phosphate is lost in urine than gained from bone mineralisation
171
Q

what is the active form of Vit D?

A

calcitriol (1,25- dihydrocholecalciferol)

172
Q

which tissue secretes calcitonin?

A

thyroid gland- parafollicular/ C cells

173
Q

squamous tumours of the lung, head and neck can sometimes produce a hormone that can cause hypercalcaemia. what is this hormone

A

PTHrP= parathyroid hormone- related peptide

this acts at parathyroid hormone receptors

174
Q

what is the serum calcium concentration?

A

2.2-2.6 mM

175
Q

what symptoms does hypocalcaemia present with?

A

<2.1 mmol/L
hyperexcitability in the nervous system (at NMJ)
Calcium raises the threshold for nerve membrane depolarisation and therefore makes it easier for the development of APs
- paraesthesia
- tetany
- paralysis
- convulsions

176
Q

what symptoms does hypercalcaemia present with?

A

> 3.0 mmol/L

  • kidney stones formation (renal calculi)
  • constipation
  • dehydration
  • kidney damage
  • tiredness
  • depression
177
Q

where do the hydroxylations of Vit D take place?

A

1- liver

2- kidney

178
Q

what is the difference between osteomalacia and osteoporosis

A

osteomalacia- normal structure but undermineralised (rickets in children- deformity of long bones)

osteoporosis- structurally degraded but fully mineralised
- decreased bone density but no increase in serum calcium levels

179
Q

what is the Cori cycle

A

term used to describe the cycle by which the lactate produced in skeletal muscle is converted back to glucose in the liver

180
Q

describe catabolism

A

oxidative and exergonic

181
Q

what effect does the hormone insulin have on the enzyme phosphofructokinase in liver?

A

increases in activity

PFK- rate limiting enzyme in glycolysis

182
Q

what substance is used to supply the ETC with high energy electrons derived from metabolic substrates

A

NADH

183
Q

transport of FAs into mitochondria requires which substance?

A

carnitine

shuttle for FA across the inner mitochondrial space

184
Q

accumulation of which substance would cause a patient’s breath to smell like pear-drops?

A

acetone

  • non enzymatic decarboxylation of acetoacetate (ketone body) forms acetone which smells like pear- drops
  • pear drop smell indicates ketone body formation with a subsequent risk of ketoacidosis
185
Q

what class of metabolite can partially replace the use of glucose as a metabolic fuel in the brain during starvation?

A

ketone bodies (acetoacetate and beta- hydroxybutyrate) can be used

186
Q

name a ketogenic AA

A

leucine / lysine

  • ketogenic as they result in the formation of acetyl- CoA
  • acetyl- CoA can be used to make ketone bodies in the liver or enter the TCA cycle
  • cannot synthesise glucose from these AA (not glycogenic)
187
Q

what are examples of ketone bodies?

A

acetoacetate, beta-hydroybutyrate, acetone

188
Q

what is promoted by insulin?

A

glucose uptake

in adipose and muscle by causing translocation of the GLUT4 glucose transporter to the plasma membrane

189
Q

which two organs can contribute to gluconeogenesis during a period of starvation

A

liver and kidney

190
Q

for approx how long can creatine phosphate be used to replenish ATP usage in skeletal muscle during max physical exertion?

A

5 secs

further ATP must be supplied by glycolysis and oxidative phosphorylation

191
Q

an increase in ADP conc in exercising skeletal muscle would promote glycolysis by increasing the activity of which enzyme?

A

phosphofructokinase

- key regulator of glycolysis stimulated by high AMP and inhibited by low ATP

192
Q

what determines whether glycolysis will result in pyruvate or lactate production in exercising skeletal muscle?

A

the supply of oxygen to muscle

193
Q

what metabolic change occurs in the liver in response to exercise?

A
  • rate of hepatic gluconeognesis would increase
  • in order to supply additional glucose for use by exercising muscle and brain
  • driven by an increase in glucagon (hormone)
194
Q

does glucagon increase or decrease during a marathon run?

A

increases

- stimulates glucneogenesis by activating PEPCK and fructose-1,6-bisphosphatase

195
Q

what symptom would be consistent with excess secretion of cortisol (hormone)

A

high plasma glucose

- stimulate gluconeogenesis in liver and inhibit glucose uptake in muscle

196
Q

the plasma conch of what hormone would increase asa a consequence of Addison’s disease?

A 
Adrenocorticotropic hormone ( ACTH)
- lack of (-) feedback from cortisol
197
Q

why does hyperpigmentation sometimes occur in patients with Addison’s disease?

A

decreased cortisol leads to increased expression of POMC

  • removal of (-) feedback from cortisol on hypothalamus leads to increased ACTH production
  • melanocyte- stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) share the same precursor molecule- POMC
  • increased POMC leads to increase in both ACTH and MSH
  • increased MSH results in hyperpigmentation
198
Q

a patient has Cushing’s syndrome caused by excess cortisol production from an adrenal tumour. what effect would this condition have on plasma ACTH level?

A

ACTH would decrease

- excess cortisol would inhibit ACTH secretion by (-) feedback

199
Q

which time of day would be best to take a blood sample for cortisol measurement if Cushing’s syndrome is suspected?

A

midnight

- should normally be low at midnight

200
Q

which exogenous steroid is typically administered to patients as part of a suppression test to diagnose Cushing’s syndrome ?

A

dexamethasone suppression test (DST) used to assess adrenal gland function

  • normal result: decrease in cortisol
  • Cushing’s = cortisol not suppressed by a low dose
201
Q

what is the synthetic analogue of ACTH used in an ACTH stimulation test

A

synACTHen

  • synthetic ACTH analogue used to test adrenal function
  • IV: normally increase plasma cortisol by >200nml/L- which can exclude Addison’s disease
202
Q

what is a potential iatrogenic cause of Addison’s disease ?

A

adrenalectomy

- iatrogenic effect= illness caused by medical examination/ treatment

203
Q

which tissue contains the greatest mass of glycogen?

A

skeletal muscle - 300g

around 100g in liver which is the other store

204
Q

what effect would glucagon have on the enzyme glycogen synthase in the liver?

A

decrease in activity

- glycogen synthase is the rate limiting enzyme in glycogen synthesis

205
Q

which effect would the hormone insulin have on the enzyme glycogen phosphorylase in muscle?

A

decrease in activity

- glycogen phosphorylase is the rate limiting enzyme in glycogen degradation

206
Q

which enzyme is a major control site in the pathway of gluconeogenesis?

A

Fructose 1,6- bisphosphatase

and PEPCK

207
Q

where does FA synthesis and oxidation occur? (different answers)

A 
synthesis= cytoplasm
oxidation= mitochondria
208
Q

what effect would the hormone insulin have on the enzyme hormone sensitive lipase?

A

decrease in activity

hormone sensitive lipase breaks down triaglyglycerol into FA and glycerol

209
Q

which class of lipoprotein particle typically contains the greatest amount of cholesterol and cholesterol ester?

A

LDL
main function is the transport of cholesterol synthesised in the liver to tissues
therefore they have the highest cholesterol content

210
Q

which class of lipoprotein particle transports dietary triacylglycerol from the intestine to tissues such as muscle and adipose tissue?

A

chylomicrons

intestine -> peripheral tissues

211
Q

which enzyme located on the capillary walls of muscle and adipose tissue facilitates the release of FAs from chylomicrons?

A

lipoprotein lipase

212
Q

what does hormone sensitive lipase do?

A

intracellular lipase that hydrolyses stored triaclyglyerols in adipose tissue to free FA.
although HSL hydrolyses triaclyglyerols, this enzyme is involved in the mobilisation of fat stores from adipose rather than loading of FAs from chylomicrons

213
Q

by what mechanism are LDL lipoprotein particles taken up by peripheral tissues?

A

receptor mediated endocytosis

214
Q

which lipoprotein particle facilities reverse cholesterol transport?

A

HDL

  • removes cholesterol from cholesterol- laden cells and return it to the liver
  • ABCA1 protein within the cell facilitates the transfer of cholesterol to HDL
  • cholesterol is then converted to cholesterol ester by LCAT
215
Q

which enzyme is inhibited by statin drugs?

A

HMG- CoA reductase

216
Q

what is the ideal plasma conc of total cholesterol?

A

less than 5mM (5mmol/L)

217
Q

which metabolite can be measured in urine to provide an estimate of muscle mass?

A

creatinine

  • breakdown product of creatine phosphate and creatine in muscle
  • usually produced at a constant rate and filtered by kidneys into urine
218
Q

which effect would insulin have on the process of protein degradation (proteolysis)?

A

decrease in activity

- after a meal- there will be sufficient AA derived from ingested protein so no need to degrade body protein

219
Q

from which AA does the body synthesise adrenaline?

A

tyrosine

  • tyrosine and phenylalanine are precursor AA for the synthesis of catecholamines such as adrenaline, NA and dopamine.
  • Thyroid hormones (T3 % T4) are also derivatives of tyrosine
220
Q

which keto acid is used by aminotransferase enzymes to funnel the amino group of other AAs to glutamate?

A

alpha- ketogluterate

221
Q

which aminotransferase enzyme is routinely measured as part of liver function test?

A

alanine aminotransferase and aspartate aminotransferase (ALT and AST)
- not normally found in plasma and therefore presence in blood test gives an indication of liver damage

222
Q

down regulation of the enzymes of the urea cycle resulting from insufficient protein intake can result in which disease state?

A

refeeding syndrome
- low protein intake has resulted in down regulation of the urea cycle resulting in ammonia toxicity of food is re-introduced too quickly

223
Q

which AA is utilised for the transport of ammonia from peripheral tissues to the liver?

A

alanine

224
Q

during the conversion of ethanol to acetaldehyde by alcohol dehydrogenase - what is also produced?

A

NADH

225
Q

does aldehyde dehydrogenase have a high or low Km for acetaldehyde?

A

low Km

- acetaldehyde toxicity normally kept to a min by aldehyde dehydrogenase

226
Q

what term is used to describe scarring of the liver cause by continuous long term liver damage?

A

cirrhosis

227
Q

what is a metabolic response to chronic alcohol consumption?

A

increased synthesis of FAs and ketone bodies

- increased acetyl- CoA from alcohol oxidation would lead to an increase in the synthesis of FAs and ketone bodies

228
Q

dihulfarim can be used to support the treatment of alcohol dependence. which enzyme is inhibited by this drug?

A

aldehyde dehydrogenase

229
Q

which reactive oxygen species is produced when molecular oxygen gains an electron?

A

superoxide

- superoxide also an important source of other reactive oxygen species such as hydrogen peroxide and hydroxyl radicals

230
Q

a disulphide bond in a protein can form between two resides of which AA?

A

thiol groups of cysteine residues

- the other sulphur containing AA, methionine, cannot form disulphide bonds

231
Q

which enzyme is involved in protecting cells from oxidative damage by converting superoxide to H2O2 and oxygen?

A

superoxide dismutase (SOD)

232
Q

which enzyme protects cells from oxidative damage by converting H2O2 to water and oxygen?

A

catalase

233
Q

which fat soluble vitamin plays an important role in protecting cells against oxidative damage by acting as a free radical scavenger?

A

vit E

  • protects cells against lipid per oxidation
  • vit c water soluble antioxidant that plays an important role in regenerating the reduced form of vit E
234
Q

in acetaminophen (paracetamol) overdose, which toxic metabolite accumulates in the liver causing damage?

A

NAPQI

235
Q

why is raised serum LDL associated with atherosclerosis?

A
  • LDL not effectively cleared by the liver as does not have apoE
  • half life for LDL in blood longer than VLDL or IDL and so is more susceptible to oxidative damage
  • oxidised LDL taken up by macrophages that transform into foam cells
  • foam cells accumulate in intimate of blood vessel walls to form a fatty streak
  • fatty streaks can evolve into atherosclerotic plaque
  • grows & encroaches on lumen of artery that can cause angina or rupture which triggers acts thrombosis by activating platelets and the clotting cascade
236
Q

what is the treatment for hyperlipoproteinaemia?

A

statins eg Atorvastatin
- reduce cholesterol synthesis by inhibiting HMG-CoA reductase
bile salt seqnestrants eg Colestipol
- bind bile salts in GI tract forces liver to produce more bile acids using up more cholesterol

237
Q

what is the difference between VLDL and HDL?

A

VLDL- made in liver to transport TAG to other tissues

HDL- made in liver and intestine to transport cholesterol from cholesterol- laden cells and return to liver

238
Q

what are the clinical signs of hyperlipoproteinaemia?

A
  • xanthelasma- yellow patches around eyes
  • tendon xanthoma- nodules on tendon
  • corneal arcus- white circle around eye
239
Q

when do chylomicrons appear in the blood?

A

present in blood normally 4-6hrs after a meal

have a ‘creamy appearance’

240
Q

what are the three key enzymes in gluconeogenesis?

A

PEPCK: converting oxaloacetate
fructose-1,6-bisphosphatase: converting fructose-1,6-bisphosphate
glucose-6-phosphatase: converting glucose-6-phosphate

241
Q

what are two enzymes that regulate glycogen metabolism

A

glycogen synthase- synthesis
glycogen phosphorylase- degradation
- irreversible reactions

242
Q

what are the key enzymes for glycogenolysis

A
  • glycogen phosphorylase alpha 1-4 or debranching enzyme alpha1-6
  • phosphoglucomutase
243
Q

what are the key enzymes for glycogenesis

A
  • hexokinase
  • phophoglucomutase
  • G1P uridylyltransferase
  • glycogen synthase alpha1-4 or branching enzyme alpha1-6
244
Q

what is phenylketonuria (PKU)?

A

autosomal recessive disorder
deficiency in phenylalanine hydroxylase
- enzyme usually converts phenylalanine into tyrosine- precursor for NA, adrenaline, dopamine, melanin, thyroid hormone and protein synthesis.
- accumulation of phenylalanine in tissue, plasma and urine
- phenylketones in urine= musty smell

245
Q

what is the treatment for phenylketonuria?

A
  • low phenylalanine diet enriched with tyrosine

- avoid high protein foods

246
Q

what is homocystinurias?

A

autosomal recessive
problem breaking down methionine
excess homocysteine in urine - elevated homocysteine associated with cardiovascular disease
affects CT, muscles, CNS and CVS

247
Q

what is the treatment for homocystinurias?

A
  • low methionine diet
  • avoid meat, fish, cheese and eggs
  • cysteine, vit B6, betaine, B12 and folate supplements
248
Q

how is ammonia toxic?

A
  • readily diffusible and toxic to the brain
  • interference with AA transport and protein synthesis
  • alkaline pH effects
  • alteration of the blood brain barrier
249
Q

which keto acid is used by aspartate aminotransferase enzymes to funnel the amino group of other AAs to aspartate?

A

oxaloacetate

250
Q

name some vitamins that act as free radical scavengers

A

vit E
- lipid soluble antioxidant that protects against lipid peroxidation
vit C
- water soluble antioxidant that regenerates reduced form of vit E

251
Q

what is a respiratory burst?

A

rapid release of superoxide and hydrogen peroxide from phagocytic cells (neutrophils and monocytes)
ROS and peroxynitrite destroy invading bacteria - antimicrobial defence system

MEH (4 decks)

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