Endocrinology Flashcards

Question

What is the significance of thionamides being secreted in milk?

Answer 1

- thyroid disease is common in women around reproductive age so you must consider pregnancy and neonatal period - patients can breast-feed on thionamides but ideally on as low a dose as possible -\> high doses of thionamides in a pregnant woman could cause foetal hypothyroidism - propylthiouracil crosses into breast milk LESS than carbimazole -\> breast-feeding woman are put on PTU over CBZ

Answer 2

18 months -\> 50:50 chance of relapse after stopping

Answer 3

o Preparation of hyperthyroid patients for surgery o Severe thyrotoxic crisis (thyroid storm)

Answer 4

- Wolff-Chaikoff Effect = the temporary reduction in thyroid hormones following ingestion of large amounts of iodine - an autoregulatory phenomenon -\> the thyroid rejects the ingested iodide, hence prevents the gland from sucking up loads of iodine and making too much thyroid hormone - KI inhibits the iodination of thyroglobulin and the generation of hydrogen peroxide

Answer 5

- very quick, a matter of hours - maximum effect after 10 days of contiuous administration - over weeks it reduces the size and vascularity of the thyroid

Answer 6

- ALLERGIC REACTION - rashes - fever - angioedema

Answer 7

- given orally or Lugol's Solution or Aqueous Iodine

Answer 8

- Graves' - Plummer's - Thyroid Cancer

Answer 9

- permanently switching off the thyroid without surgery - the method relies on the thyroid gland taking up iodine to make thyroid hormone so thyroid follicular cells take up the radioiodine so, it accumulates in the colloid -\> emits beta particles of radiation that destroy the follicular cells

Answer 10

- discomfort in the neck

Answer 11

- anti-thyroid drugs must have been discontiued 7-10 days prior to radioiodine treatment so that the thyroid gland can rev up and be really active so that it sucks up a lot of radioactive iodine when it is administered to get maximal destruction of the gland

Answer 12

- oral dose of approx. 500 MBq

Answer 13

- oral dose of circa 3000 MBq

Answer 14

o Radioactive half-life = 8 days o Radioactivity negligible after 2 months (maximum effect 2-3 months)

Answer 15

- avoid close contact with small children for several weeks - contra-indictaed in pregnancy and breast-feeding

Answer 16

- entire gland is active and smoothly enlarged

Answer 17

- single focus of activity and the rest is supressed

Answer 18

- inflamed thyroid gland where there is NO activity at all

Answer 19

- caused by a virusattacking the thyroid gland and it causing a fever - it damages the thyroid follicles and all the stored thyroxine gets released so patients present with OVERACTIVE thyroid, after a bout a month when all the thyroxine has ran out they will become hypothyroid as the damaged gland will no longer make thyroxine

Answer 20

- piainful dysphagia - hyperthyroidism - pyrexia - raised erythrocyte sedimentation rate

Answer 21

- you have to wait for all the thyroxine to have been used up before giving thyroxine to treat the hypothyroidism - drugs can be given to help with the symptoms

Answer 22

D - all the others will control thyroid function but the lugol's iodine, used for 10 days before the operation, will reduce the size and vascularity of the thyroid gland

Answer 23

- FSH - LH - GH - TSH - ACTH - prolactin

Answer 24

- decreased production of ALL anterior pituitary hormones (panhypopituitarism) or of specific hormones

Answer 25

- PROP1 mutation - this is a transcription factor that allows the development of the pituitary gland to take place - is congenital

Answer 26

o Tumours -\> hypothalamic (craniopharyngiomas) or pituitary (denomas, metastases, cysts) o Radiation -\> hypothalamic/pituitary damage (GH most vulnerable, TSH relatively resistant) o Infection -\> meningitis o Traumatic brain injury o Infiltrative disease -\> often involves pituitary stalk (neurosarcoidosis) o Inflammatory (hypophysitis) o Pituitary apoplexy -\> haemorrhage (or less commonly infarction) o Peri-partum infarction (Sheehan’s syndrome)

Answer 27

o Gonadotrophins (LH and FSH) o GH o Thyrotrophin o Corticotrophin o Prolactin deficiency is uncommon/unrecognised

Answer 28

o Secondary Amenorrhoea OR Oligomenorrhoea o Impotence o Loss of libido o Erectile dysfunction o Tiredness o Waxy skin o Loss of body hair o Hypotension - no really symptoms for growth hormone in adults

Answer 29

o develops acutely following post-partum haemorrhage resulting in PITUITARY INFARCTION - blood loss results in vasoconstrictor spasm of hypophysial arteries and this leads to: ischaemia of the pituitary (enlarged during pregnancy due to swelling of prolactin glands) and necrosis of the pituitary - develops very FAST o more prevelant in less developed countries as hypotension post-partum is more common

Answer 30

- lethargic - anorexia - weight loss - failure of lactation - failure to resume menses post-delivery o posterior pituitary usually not affected

Answer 31

- intra-pituitary haemorrhage or, less commonly, infarction - often dramatic, rapid presentation in patients with pre-existing pituitary tumours (adenomas) -\> may be first presentation of a pituitary adenoma - often causes severe headaches and visual field defects (depression on the optic chiasm) - can be precipitated by anti-coagulants

Answer 32

- pituitary apoplexy isn't specific to women

Answer 33

- diplopia (IV, VI), ptosis (III)

Answer 34

o Biochemical - basal plasma values of pituitary or target endocrine gland hormones - stimulated (dynamic) pituitary function test o Radiological - pituitary MRI

Answer 35

- most things released from the hypothalamus are released in pulses -\> single measurements are not useful -\> low or high results could be physiological

Answer 36

- done using a combined function test -\> involves the administration of various releasing hormones -\> releasing hormones are administered IV - the same thing can be done with just one releasing hormone if you're testing for a specific hypothyroidism -\> the specific test for GH is the insulin-induced hypoglycaemia test No action Mouse Gestures ![]() ![]() Back ![]() Forward ![]() Scroll up ![]() Scroll down ![]() Switch to previous tab ![]() Switch to next tab ![]() Close all tabs except current ![]() Close current tab ![]() Open new tab ![]() Close all tabs ![]() Refresh current tab ![]() Stop loading ![]() Scroll to bottom ![]() Scroll to top ![]() Reopen closed tab ![]() Go to home page

Answer 37

o specific pituitary pathology eg haemorrhage (apoplexy), adenoma o empty sella – thin rim of pituitary tissue

Answer 38

- hormone replacement therapy

Answer 39

- hydrocortisone

Answer 40

- thyroxine

Answer 41

- oestrogen - if the patient has a uterus progesterone must be given with the oestrogen - prevents endometrium hyperplasia

Answer 42

- somatotrophin

Answer 43

o children -\> pituitary dwarfism o adults -\> effects are unclear

Answer 44

o Lack of GH o Genetic -\> Down’s syndrome, Turner’s syndrome, Prader Willi syndrome o Malnutrition o Emotional deprivation (potentially due stress response effecting the growth axis) o Endocrine disorders -\> Cushing’s syndrome, Hypothyroidism, GH deficiency, poorly controlled T1DM o Systemic disease -\> Cystic Fibrosis, Rheumatoid arthritis o Malabsorption -\> Coeliac disease o Skeletal dysplasia -\> Achondroplasia, osteogenesis imperfecta

Answer 45

- GHRH is released from the hypothalamus and truggers the anterior pituitary to release GH - GH caues growth in target tissue as well as stimulating the production of IGF I and IGF II in the liver-\> IGF I mediates growth - GH is controlled in the hypothalamus by GHRH and GH

Answer 46

- a form of dwarfism caused by a GH receptor defect -\> results in low IGF I levels because GH isn't having an effect

Answer 47

- specific hypothalamic hormone defects

Answer 48

- GnRH deficiency

Answer 49

- Kallmann's Syndrome - Prader-Willi-Syndrome

Answer 50

- caused by a genetic defect where the neurones in the embryo that will go on to produce GnRH are unable to migrate to the hypothalamus -\> hypothalamus LACKS GnRH neurones - the defect also prevents the migration of the neurones that are going to develop a sense of smell resulting in various degrees of anosmia - hypogonadism -\> untreated suffers never go through puberty

Answer 51

- if they fall below their percentile on the charts within their red book

Answer 52

- trauma - pituitary tumour - pituitary surgery - cranial radiotherapy

Answer 53

o GH provocation tests in which plasma GH is measured at specific points before and aftwerwards - GHRH + ARGININE (IV) - (in combination more effective than each alone) - INSULIN (IV) – via hypoglycaemia - GLUCAGON (IM) - EXERCISE (e.g. 10 min step climbing; when appropriate)

Answer 54

o hormone replacement therapy - human recombinant GH - daily, subcutaneous injection

Answer 55

o impaired ‘psychological well being’ and reduced quality of life -\> only proved symptom - reduced lean mass - increased adiposity - increased waist:hip ratio - reduced muscle strength & bulk à reduced exercise performance - decreased plasma HDL-cholesterol & raised LDL-cholesterol

Answer 56

o improved psychological well being and quality of life - improved body composition -\> decreased waist circumference, less visceral fat - improved muscle strength and exercise capacity - more favourable lipid profile - higher HDL-cholesterol, lower LDL-cholesterol - increased bone mineral density

Answer 57

o increased risk of cardiovascular accidents -\> due to its growth promoting effects, an excess of GH can cause cardiomegaly o increased soft tissue growth, leading to e.g. cardiomegaly o expensive o increased susceptibility to cancer was thought but proved wrong

Answer 58

o symptoms associated with excess production of adenohypophysial hormones - can be due to isolated tumours but can be ectopic in origin (eg vasopressin in lung tumours)

Answer 59

- visuial field defects - often accompanied with other defects particularly cranial nerve defects

Answer 60

- fibres from the inner (nasal) part of the retinae cross

Answer 61

o bitemporal heminaopia - you lose the temporal/peripheral vision

Answer 62

o perimetry - press button when the patient can see the flashing light which builds up a visual field

Answer 63

- the syndrome is simply to much ACTH whereas the disease is due to a pituitary adenoma

Answer 64

o physiological = pregnancy and breastfeeding o pathological = prolactinoma (often microadenomas\<10nm diameter)

Answer 65

- it suppresses GnRH pulsatility - can cause secondary hypogonadism

Answer 66

- galactorrhoea (milk production when not breastfeeding) - secondary amenorrhoea or oligomenorrhoea - loss of libido - infertility

Answer 67

- loss of libido - erectile dusfunction - infertility - galactorrhoea can occur but is very uncommon

Answer 68

- dopamine binding to D2 receptors

Answer 69

- 1st line = dopamine receptor agonists therefore inhibiting prolactin and reduce the tumours size - include bromocriptine and cabergoline via oral administration o unusual that it is medical and not surgical treatment

Answer 70

- nausea and vomiting - postural hypotension - dskinesias - depression - pathological gambling

Answer 71

o in children = gigantism o in adults = acromegaly - in adults, the growth plates of the long bones have fused so there is no longer a possibility of an increase in height but you still get other effects

Answer 72

- usually benign growth hormone secreting pituitary adenoma - maybe benign but can be deadly due to pressure it can provide on cranium

Answer 73

- incidious onset -\> gradual changes over many years o increased morbidity and mortality - \> death: CVD = 60% - \> respiratory complications = 25% - \> cancer = 15%

Answer 74

o periosteal bone o cartilage o fibrous tissue o connective tissue o internal organs (cardiomegaly, splenomegaly, hepatomegaly etc.) o prognathism o enlarged supraorbital ridges o enlarged soft tissues

Answer 75

- EXCESSIVE SWEATING (HYPERHIDROSIS) - HEADACHES - enlargement of supraorbital ridges, nose, hands and feet, thickening of lips and general coarseness of features - enlarged tongue (macroglossia) - mandible grows causing protrusion of lower jaw (prognathism) - carpal tunnel syndrome (median nerve compression) - barrel chest - kyphosis

Answer 76

excess GH -\> increased endogenous glucose production and decreased muscle uptake -\> increased insulin production -\> increased insulin resisitance -\> impaired glucose tolerance (50% of patients) -\> diabetes mellitus

Answer 77

o obstructive sleep apnoea -\> bone and soft-tissue changes surrounding the upper airway lead to narrowing and subsequent collapse during sleep o hypertension o cardiomyopathy -\> hypertension, DM, direct toxic effects of excess GH on myocardium o increased risk of cancer -\> colonic polyps, regular screening with colonoscopy

Answer 78

- prolactin

Answer 79

- oral glucose tolerance o paradoxical rise of GH following oral gluscose load

Answer 80

o SURGERY is the main treatment - transphenoidal hypophysectomy o Radiotherapy - problem is that over a long period of time the patient ends up hypopituitary as a result o Chemotherapy/Drugs -\> somatostatin analogues or dopamine Agonists

Answer 81

- octreotide

Answer 82

- bromocriptine - cabergoline

Answer 83

- short-term treatment before pituitary surgery -\> reduces the size of the tumour to make surgery easier - treatment of other neuroendocrine tumours e.g. carcinoid tumours

Answer 84

- subcutaneous or intramuscular

Answer 85

o GI tract disturbances (somatostatin is produced by the small intestine) -\> gallstones o initial reduction in insulin secretion - transient hyperglycaemia -\> inhibits the production of insulin by beta cells leading to transient hyperglycaemia

Answer 86

- is the bright spot at the back of pituitray gland

Answer 87

- vasopressin (ADH) - oxytocin

Answer 88

- constriction of myometrium at parturition - milk ejection reflex

Answer 89

- osmoreceptors in the organum vasculosum

Answer 90

o central/cranial -\> absense or lack of circulating vasopressin o nephrogenic -\> end-organ (kindeys) resistence to vasopressin

Answer 91

o acquired (more common) -\> damage to neurohypophysial system - traumatic brain injury - pituitary surgery - pituitary tumours, craniopharyngioma - metastasis to the pituitary gland - e.g. breast - granulomatous infiltration of median eminence - e.g. TB, sarcoidosis o Congenital – rare - usually receptor gene mutations

Answer 92

- familial (rare) - drugs -\> LITHIUM (used to treat bi-polar disorder), dimethyl chlortetracycline (DMCT)

Answer 93

- polyuria - very dilute urine (hypo-osmolar) - thirst and increased drinking (polydipsia) - dehydration (and consequences) if fluid intake is not maintained - possible disruption of sleep with associated problems - possible electrolyte imbalance

Answer 94

- psychogenic polydipsia

Answer 95

o normal person has a tightly maintained osmolality (270-290 mOsm/kg H₂O) o diabetes insipidus = high osmolality o psychogenic polydipsia = low osmolality

Answer 96

o fluid deprivation test

Answer 97

- hypernatraemia - raised urea - increased plasma osmolality - dilute (hypo-osmolar) urine - ie low urine osmolality

Answer 98

- mild hyponatraemia -\> excess water intake - low plasma osmolality - dilute (hypo-osmolar) urine -\> ie low urine osmolality

Answer 99

- V2 receptor agonists -\> desmopressin (DDAVP)

Answer 100

- is V1 receptor agonist -\> used to treat GI bleeds

Answer 101

- nasally or orally - produces a prompt sustained decrease in urine volume and increase in urine osmolarity -\> has a very long effect so you don't need to take desmopressin too often

Answer 102

- nocturnal eneuresis (bedwetting) - haemophilia - you need V2 receptor stimulation

Answer 103

- fluid retention and hyponatraemia - abdominal pain - headaches - nausea

Answer 104

- thiazide diuretic

Answer 105

- plasma vasopressin concentration is INAPPROPRIATE for the existing plasma osmolarity -\> too much ADH for current osmolarity

Answer 106

o Signs of SIADH: - raised urine osmolarity - decreased urine volume (initially) - hyponatraemia - decrease in plasma sodium concentration due to increased water reabsorption o Symptoms of SIADH: - often asymptomatic - when Na⁺ concentration falls \< 120mM = generalised weakness, nausea and poor mental function - when Na⁺ conc. falls \<110mM = confusion, coma and death

Answer 107

- tumours (ectopic secretion) - neurohypophysial malfunction (e.g. meningitis, cerebrovascular disease) - pulmonary disease (e.g. pneumonia) - malignancy (in particular small cell lung cancer) - endocrine disease (e.g. Addison's disease) - physiological - it can happen under quite normal circumstances where AVP release is stimulated by non-osmotic stimuli (e.g. hypovolaemia, pain, surgery) - drugs (e.g. chlorpropamide) - idiopathic

Answer 108

- treat the cause (e.g. tumour) - if someone is already hyponatraemic, you need to deal with that as quickly as possible: -\> immediate = fluid restriction and longer-term = drugs that prevent vasopressin action in the kidneys (e.g. lithium, dimethyl chlortetracycline (DMCT), V2 receptor antagonists)

Answer 109

- non-peptide vasopressin analogues - tolvaptan - V2 receptor antagonist o can be used for SIADH but are very expensive so are rarely used

Answer 110

- congestive heart failure

Answer 111

- increase = nicotine - decrease = alcohol and glucocorticoids

Answer 112

o Tongue gets thick o Speech slows down o Deepening of the voice o Basal Metabolic Rate falls o Bradycardia o General weakness o Depression o Cold intolerance o Weight gain and reduced appetite o Constipation - Eventual myzoedema coma

Answer 113

- it goes up to try and stimulate the thyroid

Answer 114

- deiodinase

Answer 115

- 80% is deiodination of T4 - 20% is direct thyroidal secretion of T3

Answer 116

- thyroxine enters the target cell and is converted to T3 by deiodinase (can also be T3 that enters directly) - T3 moves to the nucleus and binds to the thyroid hormone receptor and then heterodimerises with a Retinoid X Receptor - this complex then binds to the Thyroid Response Element that causes a change in gene expression

Answer 117

- the usual thyroxine replacement is levothyroxine sodium or direct thyroxine (T4) - rarely liothyroxine sodium is used as a T3 replacement

Answer 118

- primary hypothyroidism - autoimmune or iatrogenic (post-thyroidectomy or post-radioactive iodine) - secondary hypothyridsim (pituitary tumour, post-pituitary surgery/radiotherapy)

Answer 119

- TSH levels

Answer 120

- isn't any TSH (or is very low) so middle of T4 reference range is used

Answer 121

- to treat MYXOEDEMA COMA - a very rare complication of hypothyroidism - IV liothyronine (T3) is given in this situation because the onset of action is faster than T4 - then when the patient has recovered from the coma oral thyroxine replacement is given

Answer 122

- T3 is very potent -\> very difficult to get the dose right - high T3 switches off TSH and patients show thyrotoxicosis symptoms = palpatations, tremors and anxiety - combined thyroid hormone replacement does exsist but again isn't favoured

Answer 123

- 99.97% of T4 and 99.7% of T3 are bound to thyroxine binding globulin (TBG) (not to be confused with thyroglobulin in the colloid of follicular cells)

Answer 124

- increase in pregnancy and with prolonged treatment with oestrogens and phenothiazides decreased with liver disease or if you are severely malnourished

Answer 125

- phenytoin - salicylates (e.g. aspirin)

Answer 126

- autoimmune -\> 5% of people suffer from this in their life

Answer 127

o usually associated with a low/suppressed TSH o Skeletal -\> increased bone turnover, reduction in bone mineral density therefore risk of osteoporosis o Cardiac -\> tachycardia, risk of Dysrrhythmia (particularly atrial fibrilation) o Metabolism - increased energy expenditure, weight loss o Increase b-adrenergic sensitivity -\> tremors, nervousness ARE ALL SYMPTOMS OF THYROTOXICOSIS

Answer 128

- too much cortisol

Answer 129

- centripetal obesity - moon face - buffalo hump - proximal myopathy - hypertension - hypokalaemia - red striae - thin skin and bruising - osteoporosis - diabetes

Answer 130

o exogenous - taking too many steroids o endogenous - pituitary dependent cushing’s disease (pituitary produces too much ACTH causing adrenal growth therefore too much cortisol) - ectopic ACTH from lung cancer - adrenal adenoma secreting cortisol

Answer 131

- diurnal rhythm

Answer 132

- 24h urine collection for urinary free cortisol - blood diurnal cortisol levels - low dose dexamethasone suppression test

Answer 133

- 0.5mg of dexamethasone (artificial steroid) every 6hrs for 48hrs - normally this suppress cortisol to 0 - in any cause of Cushing's Syndrome this will fail to suppress it to 0 o GOLD STANDARD

Answer 134

- inhibitors of sterid biosynthesis -\> metyrapne, ketoconazole

Answer 135

- mineralocorticoid receptor (MR) antagonists -\> spironolactone, epleronone

Answer 136

- inhibition of 11beta-hydroxylase therefore blocking steroid synthesis in the zona fasciculata - causes ACTH to rise as no cortisol is made so no negative feedback

Answer 137

o Control of Cushing's syndrome prior to surgery - cushing's patients are not good surgical candidates because they are predisposed to infection and have very thin skin - metyrapone is used to improve the patient's symptoms and promotes better post-op recovery (better wound healing, less infection) - oral metyrapone is dosed according to cortisol production (aim for mean serum cholesterol of 150-300 nmol/L) o Control of Cushing's symptoms after radiotherapy - radiotherapy is usually quite slow to work so you would give metyrapone after radiotherapy until the effects of the radiotherapy start to come about

Answer 138

o accumulation of 11-deoxycorticosterone which has mineralcorticoid properties -\> sodium retention and potassium secretion -\> salt retention -\> hypertension o all precursors are channeled towards sex steroid synthesis -\> increase in adrenal androgens -\> hirsutism and acne (more unpleasant for women is general)

Answer 139

- nausea, vomiting, dizziness - sedation - hypoadrenalism - hypertension on long-term administration - hirsuitism

Answer 140

- inhibits Cytochrome P450 side chain cleavage enzymes meaning that glucocorticoid, mineralocorticoid and sex steroid production is blocked

Answer 141

- treatment and control of symptoms prior to surgery - an anti-fungal (not licensed anymore due to its reduction on cortisol)

Answer 142

- nausea, vomiting - abdominal pain - alopecia - gynaecomastia, oligospermia, impotence, decreased libido -\> due to reduction of sex steroid production - ventricular tachycardias - hepatotoxicity -\> can be fatal - patients are monitored with regular liver function tests

Answer 143

- zona glomerulosa

Answer 144

- too much aldosterone - due to a benign adrenal cortical tumour in the zona glomerulosa

Answer 145

- hypertension and hypokalaemia (low potassium)

Answer 146

- high aldosterone and low renin

Answer 147

- is converted into several metabolites including canrenone which competitively antagonises MRs -\> blocks the action of aldosterone (sodium reabsorption and potassium secretion in the kidney tubules)

Answer 148

- prior to surgery to make the patient a better candidate - people who have bilateral adrenal hyperplasia -\> can't take both adrenals out as not enough cortisol or aldosterone would be produced

Answer 149

o spironolactone is a very non-specific drug so there are lots of side-effects - a progesterone receptor agonist so causes menstrual irregularities - an androgen receptor antagonist so it can cause gynaecomastia in men -\> clinically can't be used in men for this reason (must use much more commonly used epleronone) - GI tract irritation - renal and hepatic disease

Answer 150

- has the same mechanism with same affinity for MRs while being more specific so doesn't interfere with progesterone or androgen receptors so has less side effects - FAR MORE COMMONLY USED

Answer 151

- tumours of the adrenal MEDULLA which secrete catecholamines (adrenaline and noradrenaline)

Answer 152

- adrenaline has a rapid effect -\> from time to time (more likely after trauma) the tumour will release a lot of adrenaline -\> massive rise in bp (e.g. 300/150) -\> to the sort of level that cause sudden strokes or MIs - MAIN EFFECT - is a sudden onset of panic, you feel anxious, tachycardia and severe hypertension

Answer 153

- hypertension in a young person - episodic severe hypertension (after abdominal exam - press on adrenal causing release of NA and A) - more common in certain inherited conditions

Answer 154

- severe hypertension -\> MI or Stroke - high adrenaline -\> Ventricular Fibrillation (VF) -\> Sudden Cardiac Death

Answer 155

- first is alpha blockade - patients may need intravenous fluid as alpha blockade commences - second is beta blockade added to prevent tachycardia - once adrenalines effects have been nullified surgery to remove the gland

Answer 156

- 10% extra-adrenal (sympathetic chain) and 90% inside the adrenal - 10% are malignant - 10%are bilateral making 90% are curable by operation - phaeochromocytoma is EXTREMELY RARE

Answer 157

- CRH = corticotrophin releasing hormone - ACTH = adrenocorticotrophic hormone (corticotrophin) - aldosternone, cortisol, adrenaline and noradrenaline

Answer 158

- cholesterol

Answer 159

- aldosterone

Answer 160

- cortisol

Answer 161

- adrenaline and noradrenaline

Answer 162

- after each number adding hyrdoxylase gives you the enzyme

Answer 163

- TB Addison's Disease

Answer 164

- Autoimmune Addison's Disease

Answer 165

- congenital adrenal hyperplasia -\> caused by enzyme deficiency so hormones aren't made properly

Answer 166

- fall in blood pressure -\> no aldosterone - loss of salt in urine -\> unable to retain salt because of the lack of aldosterone -\> salt loss in urine and potassium plasma - fall in glucose -\> due to glucocorticoid deficiency - high ACTH (no -ve feedback) resulting in increased pigmentation with some vitilgo-\> ACTH is cleaved from POMC -\> the remaining part is MSH (melanocyte stimulating hormone) o eventual death due to severe hypotension -\> if this happens suddenly it is called an Addisonian Crisis

Answer 167

- low 9am cortisol and high ACTH at any time in blood tests - unresponsive/reduced amount of cortisol produced to a big dose of synthetic ACTH (synacthen)

Answer 168

- 9am cortisol = 100 (normal = 270-900) - 9.30, post IM injection of synacthen = 150 (normal = \>600)

Answer 169

- 21-hydroxylase deficiency

Answer 170

- less than 24 hours

Answer 171

- no aldosterone and cortisol - lots of sex steroids, particularly testosterone, because all pro-hormones are channelled down that pathway

Answer 172

- as a neonate with salt losing Addisonian crisis - floppy baby - before birth if a previous child had suffers from CAH

Answer 173

- ambiguous genitalia in girls due to the excess testosterone -\> virilisation - fusion of labia into a scrotum like structure - if this is noticed they are keep in hospital to prevent arrest - can be prevented by giving the mother some steroid in pregnancy if there is a known risk of 21-hydroxylase deficiency

Answer 174

- low levels of cortisol and aldosterone but crucial enough to survive so they present at any age - excess sex steroid -\> often misdiagnosed as PCOS or other similar disease

Answer 175

- boys = precocious/early false puberty - girls = hirsutism, virilisation and acne

Answer 176

- acts as an aldosterone receptor agonist so behaves as if there is too much aldosterone -\> hypertension and hypokalaemia - sex hormones are also in excess so virilisation, hirsutism etc - lack of cortisol and aldosterone -\> aldosterone issues dont present due to reasons above

Answer 177

- low cortisol and sex steroids - 11-deoxycorticosterone and aldosterone are high

Answer 178

- never go through puberty -\> usually present around pubertal age - hypertension without addisonian crisis because they have aldosterone - borderline hypoglycaemia - lots of infections because you need cortisol to cope with the stress of infection

Answer 179

- androgens and oestrogens

Answer 180

- aldosterone -\> release is stimulated by renin in the renin-angiotensin system - hyperkalaemia, hyponatraemia, drop in renal blood flow and beta-1 adrenoceptor stimulation

Answer 181

- GR = wide distribution, selective for glucocorticoids, low affinity for cortisol - MR = descrete distribution to the kidney, don't destingiush between aldosterone and cortisol, high affinity to cortisol

Answer 182

- 11b-hydroxysteroid dehydrogenase deactivates cortiol into cortisone

Answer 183

- the 11b-hydroxysteroid dehydrogenase system becomes overwhelmed so potassium is excreted due to activation of MRs - the same mechanism cause hypertension by absorbing sodiuma nd water

Answer 184

- cortisol and hydrocortisone have the same structure, it's just that cortisol is endogenous and hydrocortisone is synthetic - can be used to treat Addison's disease/crisis - at high doses it can cause MR activation because it overwhelms the 11b-hydroxysteroid dehydrogenase system just like cortisol

Answer 185

- a glucocortcoid with weak mineralocortioid activity - tends to be used as an immunosuprressive

Answer 186

- very POTENT glucocorticoid -\> used clinically for things like brain metastases where there is a lot of oedema -\> used as an acute anti-oedema agent - NO mineralocorticoid effect

Answer 187

- an aldosterone analogue -\> used as an aldosterone substitute in Addison's disease - NOT a glucocorticoid -

Answer 188

- all can be given orally - in acute situations they are given parenterally (IV or IM)

Answer 189

- binding to plasma proteins (corticosteroid binding globulin and albumin) - hydrocortisone is about 90-95% bound - prednisolone is less bound and dexamethasone and fludrocortisone are even less bound - fludrocortisone is only bound to albumin

Answer 190

- primary = hydrocortisone and fludrocortisone - secondary = hydrocortisone -\> is a porblem with the pituitary and not adrenal so aldosterone isn't affect as renin-angiotensin system is fine

Answer 191

- FIRSTLY = 0.9% NaCl for rehydration - then high dose of hydrocortisone (IV or IM) - 5% dextrose if hypoglycaemic

Answer 192

- cortisol replacement -\> hydrocortisone or dexamethasone - replace aldosterone -\> fludrocortisone - suppress ACTH -\> reduced adrenal androgen production

Answer 193

o17a-hydroxyprogesterone levels o clinical assessments of patients complaintst: - cushingoid - glucocorticoid dose too HIGH - hirsuitism/acne - glucocorticoid dose too LOW (so ACTH is high)

Answer 194

- when the patient is vunerable to stress - minor illness = x2 normal dose - surgery = IV or Im hydrocortisone in the build up to the generla anaesthetic

Answer 195

- Follicular Phase - Ovulation - Luteal Phase

Answer 196

- LH stimulates production of oestradiol and progesterone in the ovaries - FSH stimulates follicular development and inhibin - by around day 10, the leading follicle develops into a Graffian Follicle - oestrogen initially has negatively inhibits LH and FSH secretion - so in the follicular phase their HPG axis is basically the same as men

Answer 197

- once the oestrogen levels reach a certain point, it switches from negative feedback to positive feedback - it increases GnRH release and increases LH sensitivity to GnRH -\> leads to a mid-cycle LH surge -\> triggers ovulation from the leading follicle - if implantation does NOT occur, the endometrium is shed (menstruation), but if implantation does occur you have pregnancy

Answer 198

- inability to conceive after 1 year of regular uprotected sex

Answer 199

- 1/6 couples are affected - males = 30% - females = 45% - unknown = 25%

Answer 200

- high GnRH - high LH and FSH - low testosterone/oestradiol

Answer 201

- low FSH and LH - low testosterone/oestradiol - could also be a low GnRH if it hypothalamic

Answer 202

· Loss of libido · Impotence · Small testes · Decreased muscle bulk · Osteoporosis (testosterone has an anabolic action in the bone)

Answer 203

- hypothalamic-pituitary disease - primary gonadal disease - hyperprolactinaemia - adrogen receptor deficiency

Answer 204

- Hypopituitarism -\> pituitary is not working properly -\> secondary gonadal failure - Kallman’s Syndrome (anosmia (lack of smell) and low GnRH) -\> GnRH neurones migrate forwards with olfactory neurones hence link - Illness/underweight -\> due to low levels of leptin -\> body knows you're underweight -\> it's not an appropriate time to reproduce)

Answer 205

- congenital: Klinefelter's syndrome - acquired: testicular torsion, chemotherapy

Answer 206

- LH, FSH and testosterone blood tests -\> if all low then pituitary (look at an MRI) - prolactin -\> check for hyperprolactinaemia - sperm count and motility - chromosomal analysis -\> Klinefelter's (XXY)

Answer 207

- Azoospermia = absence of sperm in ejaculate - Oligospermia = reduced numbers of sperm in ejaculate

Answer 208

o replacement testosterone for all patients -\> increase their muscle bulk and protect against osteoporosis o for fertility (if hypothalamic/pituitary disease) -\> subcutaneous gonadotrophins (LH and FSH) to stimulate testosterone release (don’t want to switch off pituitary functions so can’t give straight testosterone because that will have negative feedback) -\> induces spermatogenesis o dopamine agonist for hyperprolactinaemia -\> main hypothalamic influence over prolactin release and it has a negative effect on prolactin release

Answer 209

· Interstitial Leydig cells of the testes · Adrenal cortex (males and females) · Ovaries · Placenta · Tumours

Answer 210

· Development of the male genital tract · Maintains fertility in adulthood · Control of secondary sexual characteristics · Anabolic effects (muscle, bone)

Answer 211

o 98% is protein bound

Answer 212

o in different tissues you get testosterone being converted to other things - 5 a-reductase converts testosterone to dihydrotestosterone (DHT), in muscle and bone, which then acts on androgen receptors (AR) - aromatase, found in brain and adipose tissue, can convert testosterone to 17b-Oestradiol (E2) which acts via the oestrogen receptors (ER) -\> mechanism which may explain obesity causing infertility - DHT and E2 receptors act via nuclear receptors -\> are intracellular -\> have to go into the nucleus to have an effect

Answer 213

o testosterone in adulthood will increase: - lean body mass - muscle size and strength - bone formation and bone mass (in young men) - libido and potency o it will NOT restore fertility -\> requires treatment with gonadotrophins to restore normal spermatogenesis

Answer 214

· Amenorrhoea · Polycystic Ovarian Syndrome (PCOS) · Hyperprolactinaemia

Answer 215

- failure to develop spontaneous menstruation by the age of 16 years -\> likely to be an abnormal puberty -\> could be congenital

Answer 216

- absence of menstruation for 3 months in a woman who has previously had cycles

Answer 217

- irregularly long cycles

Answer 218

o PREGNANCY o Lactation -\> progesterone suppresses menstration o Ovarian Failure: - premature ovarian insufficiency (early menopause) - ovariectomy - chemotherapy - ovarian dysgenesis (Turner's Syndrome (45 X)) - lacking an X chromosome

Answer 219

- thick neck tissue with further swelling (cystic hygroma) - heart and kidney issues - short stature - cubitus valgus (where the forearm is angled away from the body to a greater degree than normal when fully extended) - gonadal dysgenesis (defective development)

Answer 220

o Hypothalamic/pituitary disease o Kallmann's syndrome o Low BMI o Post-pill amenorrhoea (downregulates the hypothalamus and pituitary) -\> if you use the pill for a long time then periods don’t come back for around 12 months after cessation of use -\> why it is advised that you stop using the pill every 4 years o Hyperprolactinaemia o Androgen excess: gonadal tumour

Answer 221

- Pregnancy Test - LH, FSH and Oestradiol -\> hard due to changes in natural cycle - Day 21 Progesterone -\> in the second half of the menstrual cycle the progesterone rises over a prolonged period of time -\> there should be a rise in progesterone around this time to show that they are ovulating - Prolactin -\> hyperprolactinaemia - Thyroid function test -\> hyper- and hypothyroidism can cause problems with periods - Androgen blood test (testosterone, androstenedione, DHEAS) - Chromosomal Analysis (Turner's) - Ultrasound Scan Ovaries/Uterus

Answer 222

- Treat the cause (e.g. low weight) - Primary Ovarian Failure = Hormone Replacement Therapy - Hypothalamic/pituitary disease -\> HRT for oestrogen replacement but for FERTILITY = gonadotrophins (LH and FSH) -\> part of IVF treatment

Answer 223

o Need TWO of the following: - polycystic ovaries on the ultrasound scan - oligoovulation/anovulation - clinical/biochemical androgen excess

Answer 224

· Hirsutism – male pattern hair growth · Menstrual cycle disturbance · Increased BMI makes the symptoms worse

Answer 225

- Metformin -\> insulin sensitiser used in type II diabetes - Clomiphene -\> anti-oestrogenic effect in the hypothalamo-pituitary axis -\> binds to oestrogen receptors in the hypothalamus thereby blocking the negative feedback -\> results in an increase in GnRH and gonadotrophin secretion -\> kick-starts the HPG axis for short periods for fertility - Gonadotrophin therapy as part of IVF treatment

Answer 226

- dopamine has a negative effect on prolactin release, is the main hypothalamic hormone controlling prolactin release - TRH has a mild stimulatory effect - prolactin stimulates the production of milk in lactating women - if it becomes dysregulated it will switch off gonadal function via LH actions on the ovaries and testes -\> natural contraceptive just after birth - also reduces GnRH pulsatility so that it is released basally all the time rather than in regular pulses

Answer 227

- DOPAMINE ANTAGONISTS -\> anti-emetics (metoclopramide) or anti-psychotics (phenothiazines) \*\* - PROLACTINOMA \*\* - COMPRESSION ON THE STALK DUE TO A PITUITARY ADENOMA \*\* - hypothyroidism - PCOS - eestrogens (oral contraceptive pill), pregnancy, lactation - idiopathic

Answer 228

- galactorrhoea (discharge unrelated to breastfeeding) - reduced GnRH secretion?LH action leads to hypogonadism - if its due to prolactinoma -\> headaches and visual field defects

Answer 229

o Treat the cause - e.g. stop the drugs if that's what's causing it if it is possible (e.g. anti-psychotics can’t always be stopped, it’s a balancing act) o Dopamine Agonists -\> bromocriptine or cabergoline -\> also causes a decrease in the size of the tumour if it is being caused by a prolactinoma o Pituitary surgery but is rarely needed (because drugs usually work)

Answer 230

- 1 -\> prolactin switches off GnRH pulsitivity so FSH and LH would be low as well as oestradiol

Answer 231

- permanent cessation of menstraution due to a lack of ovarian follicular activity

Answer 232

- the periiod of transition in which menstraution become irregular

Answer 233

- 51 -\> (45-55) - before 40 is deemed to be premature

Answer 234

- hot flushes - urogenital atrophy and dyspareunia (difficult or painful sexual intercourse) -\> due to vaginal atrophy - sleep disturbance - depression - decreased libido - joint pain o symptoms usually diminish/disappear with time

Answer 235

- levels of oestradiol and inhibin B fall due to follicular atresia -\> less negative feedback so gonadotrophin levels rise - a 55-year old women is expected to have high LH and FSH

Answer 236

o osteoporosis - caused by oestrogen deficiency -\> oestrogen is an anabolic hormone -\> in osteoporosis there is less matrix and that predisposes these patients with oestrogen deficiency to osteoporotic fractures - 10-fold increase in the risk of fracture in a post-menopausal woman o Cardiovascular Disease - oestrogen is protective against CVD before menopause - women have the same risk as men after the age of 70

Answer 237

- usually oestrogen + progesterone -\> can't just give oestrogen as is increases the risk of endometrial carcinoma (progesterone inhibits the proliferation) - if the patient has had a hysterectomy then oestrogen only can be given

Answer 238

o Oral oestradiol o Oral conjugated equine oestrogen o Transdermal (patch) oestradiol o Intravaginal

Answer 239

- Cyclical -\> oestradiol every day and for the last 12-14 days you take some progesterone - Continuous Combined -\> a little bit of oestrogen and a little bit of progesterone every day

Answer 240

- for disabling hot flushes

Answer 241

- very well absorbed but it has a low bioavailabitility due to extensive first pass metabolism

Answer 242

- oestrone sulphate (conjugated oestrogen) - ethinyl oestradiol: semi-synthetic oestrogen -\> form that's used in oral contraceptives o provides protection from first pass metabolism

Answer 243

- Breast Cancer - Venous Thromboembolism (VTE) - Stroke - Gallstones o absolute risk of complications for healthy symptomatic postmenopausal women in their 50s taking HRT for five years is very low but there is a relative risk o MUST consider the circumstance of the patient e.g. family history of breast cancer

Answer 244

- there is an increased risk of CHD with HRT - younger women had no problem, they had no increased risk but those who were in their 60s and started HRT, had an increased risk of CHD - it is about the timing of exposure -\> older patients who are started on HRT have a higher risk of CHD due to baseline disease Back

Answer 245

- lipid profile and endothelial function however, synthetic progestins negates these beneficial effects

Answer 246

- synthetic prohormone which has oestrogenic, progestogenic and weak androgenic effects - reduces the risk of fracture - increase the risk of STROKE (RR: 2.2) and possibly breast cancer

Answer 247

o Selective Oestrogen Receptor Modulator (SERM) o it is tissue selective: - bone - it has oestrogenic effects = reduces the risk of fracture - breast and uterus - it has anti-oestrogenic effects = this reduces the risk of breast cancer o however, raloxifene is associated with an increased risk of fatal stroke and VTE o HRT used to be prescribed to women as a first line treatment of osteoporosis but it is NOT any more because you have other treatments like oral bisphosphonates which are not associated with a risk of breast cancer -\> however, if someone has menopausal symptoms then HRT is the treatment of choice

Answer 248

- anti-oestrogenic on breast tissue ## Footnote - used to treat oestrogen-dependent breast tumours and metastatic breast cancers

Answer 249

- occurs to 1% of women o Autoimmune o Surgery o Chemotherapy o Radiation

Answer 250

- oestrogen in the oral contraceptive is often ethinyl oestradiol - progestogen in the pill is levonorgestrel or norethisterone - take it for 21 days and stop for 7 days

Answer 251

- suppresses the hypothalamus and pituitary (both E and P do this) - progesterone also thickens cervical mucous (this makes it more difficult for the sperm to pass through)

Answer 252

- when oestrogens are contra-indicated - this is if there is a risk of THROMBOSIS -\> oestrogen has pro-coagulant effects so progesterone is used instead - less effective than the combined contraceptive but if there are contra-indications (such as in a smoker) then the progesterone only contraceptive is the best option

Answer 253

- must be taken at the same time every day due to a short half-life

Answer 254

- mirena coil

Answer 255

- copper IUD - levonorgestrel - ulipristal

Answer 256

- affects sperm viability and function -\> inhibits fetilisation

Answer 257

- in the overweight as its effectiveness isn't compromised

Answer 258

- a high progesterone dose

Answer 259

o Anti-progestin activity o Delay ovulation by as much as 5 days o Impairs implantation

Answer 260

- copper IUD = 5-7 days - levonorgestrel = 72 hours - ulipristal = 5 days

Answer 261

- 1 in a million manages the journey of 100,000 times the length of a sperm

Answer 262

- testosterone is converted to oestrogen by aromatase

Answer 263

- within the rete testis and early epididymis under control of oestrogen

Answer 264

- energy for the journey - coating of the surface of the spermatozoon

Answer 265

- vas deferens concentration of spermatozoa is higher than later on in the reproductive tract once other fluids have been added

Answer 266

- vas deferens towards the bottom end

Answer 267

- 15-120x10⁶/ml (average has 2-5 ml of seminal fluid

Answer 268

- spermatoza - seminal fluid - leucocyte - potentially viruses -\> hepatitis B, HIV etc

Answer 269

- mainly = accessory sex glands = prostate, bulbourethral gland and the seminiferous tubules

Answer 270

- achieving fertilisation capacity takes place in the ionic and proteolytic environment of the fallopian tube

Answer 271

- loss of glycoprotein coat - change in surface membrane characteristics - develop whiplash movement of tail

Answer 272

- oestrogen - calcium

Answer 273

- spermatozoon binds to the ZP3 glycoprotein on the zona pellucida -\> once bound to ZP3, progesterone stimulates calcium influx into the spermatozoon - results in the calcium-dependent acrosome reaction - enables an exposed spermatozoon recognition site to bind to a second glycoprotein (ZP2) -\> once ZP2 has bound, the acrosome releases its enzymes allowing penetration of the zona pellucida so that the head of the spermatozoon can enter the ovum Back

Answer 274

- fallopian tube

Answer 275

o leads immediately into zonal reaction - cortical granules release molecules which degrade the zona pellucida (including ZP2 and ZP3) -\> prevents further binding of other sperm - also calcium dependent o explusion of the second polar body

Answer 276

- conceptus continues to divide as it moves down the fallopian tube to the uterus (3-4 days) - until implantation, the developing conceptus receives its nutrients from uterine secretions - cell division continues you will have a ball of cells with the outside cells receiving the nutrients but the inner cells will be receiving less and less nutrients - the free-living phase will last about 9-10 days

Answer 277

- luteal phase -\> oestrogen and progesterone will be high

Answer 278

- compactation into 8-16 cell morula - followed by blastocyst formation

Answer 279

o Inner cell mass - becomes the embryo o Trophectoderm - becomes the chorion (which becomes the placenta)

Answer 280

- increasing progesterone : oestrogen ratio in luteal phase

Answer 281

- attachment phase -\> outer trophoblast cells make contact with the uterine surface epithelium -\> establises a system for getting the nutrients from the mother to all the cells within the embryo - decidualisation phase -\> deeper implantation into the underlying uterine stromal tissue occuring within a few hours

Answer 282

- progesterone domination in the presence of oestrogen

Answer 283

o Leukaemia Inhibitory Factor (LIF) - from endometrial secretory glands -\> stimulates attachment of blastocyst to the endometrial cells o Interleukin-11 (IL-11) - from endometrial cells -\> released into the uterine fluid

Answer 284

o endometrial changes due to progesterone - glandular epithelial secretion - glycogen accumulation in stromal cell cytoplasm - growth of capillaries - increased vascular permeability

Answer 285

- mainly IL-11 - histamine - certain prostaglandins - TGFb - promotes angiogenesis

Answer 286

- hCG (produced in the placenta) is vital for the first 6 weeks at least as its purpose is to replace LH which will be low due to high oestrogen and progesterone -\> in a normal menstrual cycle, the oestrogen and progesterone levels will eventually fall and you'll get menstruation - to maintain the stimulation of oestrogen and progesterone, hCG is being produced by the trophoblast cells -\> hCG binds to LH receptors on the corpus luteum hence replacing the effects of LH - after about 5 weeks or so, the placenta will have taken over the production of hormones so the ovaries are no longer necessary - oestrogen and progesterone levels increase throughout pregnancy and right until the end, progesterone remains the DOMINANT influence

Answer 287

- mother provides the precursors which tends to be pregnenolone which leads to progesterone -\> progesterone is then going to lead to steroid production by the foetus (in the foetal adrenals) - maternal AND foetal adrenals produce a precursor (which is an androgen) - dehydroepiandrosterone sulfate (DHEAS) - 16a-hydroxy-DHEAS is then taken up by the placenta to produce OESTRIOL - DHEAS is also used by the placenta to produce small amounts of oestrone and oestradiol

Answer 288

- oestriol - molecule for molecule, weaker than oestradiol but it is produced in large amounts during pregnancy - source of oestriol is placenta

Answer 289

- looking at the ratio of oestriol : oestradiol and oestrone or the ratio of oestriol : total oestrogens and you see a change

Answer 290

- hGH (human growth hormone) decreases as the placental hGH-variant increases towards term - kiss peptin also increases 1000s of times to act as a natural contraception by down regulating the axis

Answer 291

- suckling stimulates neural pathways to the hypothalamus and on to the pituitary - the neurohypophysis secretes oxytocin and the adenohypophysis secretes prolactin - prolactin = promotion of milk synthesis - oxytocin = promotoin of milk ejection

Answer 292

- parturition is all about contraction of actin and myosin filaments which requires CALCIUM -\> to initiate contraction you need to increase the intracellular calcium concentration - oestrogen stimulates production of prostaglandins by the endometrial cells -\> prostaglandins stimulates the production and release of calcium into the cytoplasm from intracellular stores o Main Point: OESTROGEN tends to INCREASE the chance of contraction - progesterone has the OPPOSITE EFFECT TO OESTROGEN -\> inhibits prostaglandin synthesis and oestrogen receptors -\> keeps the effects of oestrogen under control - once the foetus reaches a certain size, the production of steroids is switched from the production of progesterone to the production of oestrogen (oestrogen dominates) - at parturition, oxytocin will be released which will bind to its receptor and open calcium channels allowing calcium ions to move in from outside Back

Answer 293

o interactive system between PTH and vitamin D o as serum calcium falls, you get an increase in PTH (parathyroid hormone) - PTH mobilises calcium from bone to increase plasma calcium - direct effect on the kidneys to increase reabsorption of calcium in the kidneys - stimulates an increase in plasma calcium indirectly via the activation of vitamin D (calcidiol from liver to calcitriol/active vitamin D) o calcitriol then has two main effects to increase serum calcium: - increased calcium absorption in the intestines - increased calcium mobilisation in bone

Answer 294

- act on oesteoblasts to cause them to release RANKL -\> RANKL activates osteoclasts

Answer 295

- PTH - FGF23

Answer 296

- inhibit Na⁺ and PO₄^3- transporter in the kidneys - negative feedback on calcitriol -\> less PO₄^3- reabsorption from the gut

Answer 297

- renal 1 alpha-hydroxylase - stimualted by PTH

Answer 298

- Ca²⁺ absorption in the gut - Ca²⁺ maintenance in the bone - increased renal Ca²⁺ reasbsorption - ve feedback on PTH

Answer 299

- diet - lack of sunlight - gastrointestinal malabsorptive states -\> liver disease, coeliac, IBD - renal failure - receptor defects (autosomal recessive)

Answer 300

o Softening of bone - you are unable to bear the weight of the rest of the body so you get the characteristic bowing of the legs o Bone deformities o Bone pain o Severe proximal myopathy

Answer 301

- convulsions - arrhythmias - tetany - parasthesia (hands, mouth, feet, lips) o CATs go Numb

Answer 302

- sensitises excitable tissues -\> muscle cramps/tetany, tingling

Answer 303

- Chvostek's - Trousseau's

Answer 304

- tap the facial nerve just below the zygomatic arch - POSITIVE response = twitching of the facial muscles - indicates neuromuscular irritability due to hypocalcaemia

Answer 305

- inflation of the blood pressure cuff for several minutes induces carpopedal spasm (aka neuromuscular irritability due to hypocalcaemia) - very painful so isn't done for long

Answer 306

- Vitamin D deficiency - hypoparathyroidism (low PTH) -\> surgical, auto-immune, magnesium deficiency - PTH resistance (e.g. pseudohypoparathyroidism) - renal failure -\> impaired 1a-hydroxylase -\> decreased production of calcitriol

Answer 307

- stones - renal effects -\> polyuria + thirst can go onto cause nephrocalcinosis (deposition of calcium in the kidneys), renal colic, chronic renal failure - abdominal moans - GI effects -\> anorexia, nausea, dyspepsia, constipation, pancreatitis - psychic groans - CNS effects -\> fatigue, depression, impaired concentration, altered mentation, coma (the last three only tend to occur when calcium concentration is \> 3 mmol/L) o Stones, Moans and Groans

Answer 308

The first two causes are responsible for 90% of cases of hypercalcaemia - PRIMARY HYPERPARATHYROIDISM -\> e.g. due to a parathyroid adenoma which becomes too busy and produces excessive amounts of PTH - MALIGNANCY - TUMOURS/METASTASES -\> bone metastases where increased bone turnover causes an increase in serum calcium plus tumours can also produce PTH-related peptide - conditions with a high bone turnover -\> hyperthyroidism, Paget's Disease - Vitamin D excess (rare)

Answer 309

- normally, there is negative feedback on PTH by calcium so if serum calcium rises, PTH will decrease - in primary hyperparathyroidism a parathyroid adenoma secretes PTH autonomously and is not responding to negative feedback o Calcium - HIGH o PTH - HIGH (unsuppressed) - malignancy is a nother major cause but serum results show low PTH with high calcium -\> check for bony metastases

Answer 310

o In children = Rickets o In adults = Osteomalacia

Answer 311

- plasma 25-hydroxycholecalciferol = usually LOW - plasma calcium = LOW - PTH = HIGH -\> secondary hyperparathyroidism that can make plasma calcium appear normal - plasma phosphate = LOW

Answer 312

o In patients with normal renal function -\> 25-hydroxy vitamin D (inactive) - either as ergocalciferol (D2) or cholecalciferol (D3) - patient can convert this to calcitriol via 1a hydroxylase o In patients with renal failure -\> active Vitamin D (alpacalcidol) - don't have their own 1a hydroxylase activity, so they can’t activate 25-hydroxy vitamin D preparations

Answer 313

o excessive treatment with active metabolites of vitamin D -\> only due to the potency of alfacalidol -\> lots and lots of Vitamin D is required to be intoxicating o Granulomatous Disease - e.g. sarcoidosis, leprosy and tuberculosis - macrophages in the granuloma tissue can convert 25-hydroxycholecalciferol to the active metabolite 1,25-dihydroxycholecalciferol

Answer 314

- synthesise osteoid and participate in mineralisation/calcification of osteoid (bone formation)

Answer 315

- release lysosomal enzymes which breakdown bone (bone resorption)

Answer 316

- an important molecule that activates osteoclasts from precursor form -\> more mature osteoclasts = more bone resorption

Answer 317

- RANKL expressed on osteoblast surface - RANKL binds to RANK-R to stimulate osteoclast formation and activity - osteoblasts express receptors for PTH and calcitriol -\> regulate balance between bone formation & resorption

Answer 318

- cortical (hard) bone -\> outer area - trabecular (spongy or trabecular) bone -\> inner area o both formed in a lamellar pattern = collagen fibrils laid down in alternating orientations, mechanically strong

Answer 319

- bone with disorganised collagen fibrils -\> far weaker than healthy bone

Answer 320

- inadequate mineralisation of newly formed bone matrix (osteoid) -\> bone remains newly formed and therefore soft

Answer 321

- CHILDREN o affects cartilage of epiphysial growth plates and bone o skeletal abnormalities (bowed legs) and pain, growth retardation, increased fracture risk

Answer 322

- ADULTS o after epiphyseal closure o skeletal pain, increased fracture risk, proximal myopathy

Answer 323

- stress fractures -\> normal stresses on abnormal bone cause insufficiency fractures, particularly in Looser Zones -\> these include the pelvis and tibia which leads to a Wide Waddling gait

Answer 324

- decreased renal function = decrease in the production of calcitriol and phosphate excretion so plasma phosphate increases - the decrease in calcitriol production will cause a decrease in calcium absorption from the intestines while phosphate plasma concentration rises both leading to hypocalcaemia - hypocalcaemia will stimulate PTH release -\> PTH will break down bone matrix in order to try and restore the blood calcium concentration to the normal level -\> hypocalcaemia decreases bone mineralisation - combination of the increased bone resorption and decreased bone mineralisation will lead to osteitis fibrosa cystica - imbalance between calcium and phosphate you can get some of it forming the main salts which can be deposited in extra-skeletal tissue causing vascular calcification

Answer 325

- radiolucent bone lesions due to osteoclastic bone resorption due to high PTH -\> very suspectible to fractures - feature of osteitis fibrosa cystica

Answer 326

- hyperphosphataemia -\> low phosphate diet and phosphate binders to reduce GI phosphate absorption - alphacalcidol -\> e.g. calcitriol analogues - parathyroidectomy in tertiary hyperparathyroidism

Answer 327

- a condition of reduced bone mass (fewer trabeculae) and a distortion of bone microarchitecture which predisposes to fracture after minimal trauma - clinically having a bone mineral density (BMD) that is 2.5 standard deviations (SD) or more below the average value for young healthy adults

Answer 328

- in a DEXA -\> dual energy x-ray absorptiometry - measures in femoral neck and lumbar spine

Answer 329

o Post-menopausal Oestrogen Deficiency o Age-related deficiency in bone homeostasis (men and women) o Hypogonadism in young men and women o Endocrine conditions -\> cushing's syndrome, hyperthyroidism, primary hyperparathyroidism o Iatrogenic -\> prolonged use of glucocorticoids, heparin

Answer 330

- Oestrogen (HRT)/Selective Oestrogen Receptor Modulators - Bisphosphonates - Denusomab - Teriparatide

Answer 331

- anti-resoptive effect on bone -\> prevents bone loss

Answer 332

o increased risk of breast cancer o venous thromboembolism o women with an intact uterus need additional progestogen to prevent endometrial hyperplasia/cancer

Answer 333

o tissue-selective ER ANTAGONISTS/anti-oestrogens -\> e.g. TAMOXIFEN - has oestrogenic activity in the bone -\> however, it has oestrogenic effects on the endometrium which limits its use in osteoporosis - tissue-selective ER AGONISTS -\> e.g. RALOXIFENE - has selectivity oestrogenic activity in bone and anti-oestrogenic activity in breast and uterus - isn't as widely used due to risk of venous thromboembolism and stroke No action Mouse Gestures ![]() ![]() Back ![]() Forward ![]() Scroll up ![]() Scroll down ![]() Switch to previous tab ![]() Switch to next tab ![]() Close all tabs except current ![]() Close current tab ![]() Open new tab ![]() Close all tabs ![]() Refresh current tab ![]() Stop loading ![]() Scroll to bottom ![]() Scroll to top ![]() Reopen closed tab ![]() Go to home page

Answer 334

- bisphosphonates

Answer 335

- binds avidly to hydroxyapatite and is ingested by osteoclasts -\> impairs the ability of osteoclasts to resorb bone and decreases maturation of osteoclasts from their precursors - possibly promotes osteoclast apoptosis o NET RESULT = REDUCED BONE TURNOVER

Answer 336

o osteoporosis - first line treatment o malignancy -\> particularly helpful when associated to hypercalcaemia or to reduced bone pain from metastases o paget's disease -\> reduces bony pain o severe hypercalcaemic emergency -\> after IV saline to REHYDRATE

Answer 337

- oesphagitis if given orally -\> may require switch from oral to IV preparations - flu-like symptoms -\> often this is limited to the first dose - osteonecrosis of the jaw -\> greatest risk in cancer patients receiving IV bisphosphonates - atypical fractures -\> might reflect over-suppression of bone remodelling in prolonged bisphosphonate use

Answer 338

- is a human monoclonal antibody - binds to RANKL and inhibits osteoclast formation and activity -\> inhibits osteoclast-mediated bone resorption

Answer 339

- subcutaneously every 6 or 12 months

Answer 340

- denosumab

Answer 341

- is a recombinant PTH (of 34 AA) - increases bone formation and resorption but FORMATION OUTWEIGHS RESORPTION

Answer 342

- very active (increased), localised but disorganised bone metabolism - usually slowly progressive

Answer 343

- excessive bone resorption occurs due to osteoclastic overactivity -\> this is followed by compensatory increase in bone formation (osteoblasts) - causes new bone formation = WOVEN bone -\> structurally disorganised and mechanically weaker than normal adult lamellar bone -\> leads to bone frailty, hypertrophy and deformity

Answer 344

- abnormal, large osteoclasts in excessive numbers - a disease of the elderlt -\> only appears after 50-60 - men and women are affected equally - common in the UK -\> maybe genetic

Answer 345

· Pelvis · Femur · Spine · Skull (associated with hearing loss) · Tibia

Answer 346

- bone pain - increased vascularity -\> warmth over affected bones - deafness -\> cochlear involvement - radiculopathy -\> due to nerve compression - multiple fractures - increased bone width

Answer 347

o High Plasma Alkaline Phosphatase (ALP) - calcium is normal o Radiology demonstrating variable features -\> loss of trabecular (spongy/cancellous) bone, increased density, deformity o Radioisotope (Technetium) scanning can be performed to indicate the areas of involvement

Answer 348

- bisphosphonates – very helpful for reducing bony pain and disease activity - simple analgesia

Answer 349

- key area of the brain (within the hypothalamus) involved in food intake regulation - is a circumventricular organ - meaning that it has an incomplete blood-brain barrier thus allowing access to peripheral hormones -\> allows the arcuate nucleus to integrate peripheral and central feeding inputs

Answer 350

o Stimulatory -\> NPY + Agrp neurons o Inhibitory -\> POMC neurons

Answer 351

- arcuate nucleus - paraventricular nucleus

Answer 352

- under normal conditions, the POMC, from arcuate nucleus, will be broken down to a-MSH which is an endogenous agonist of the MC4R (paraventricular nucleus) -\> the reason why you aren't hungry all the time is because of this a-MSH tone - you trigger hunger by the release of Agrp from the arcuate nucleus which is an endogenous antagonist of MC4R - when you need to eat, you increase Agrp activity, block the inhibitory signal of a-MSH and stimulates food intake

Answer 353

- POMC and MC4 receptor - NO NPY or Agrp

Answer 354

- Ob genes codes for leptin

Answer 355

- white adipose tissue -\> tells brain how much fat storage there is and therefore regulates eating

Answer 356

- leptin deficiency - Prader-Willi Syndrome

Answer 357

- decreased food intake - increased thermogenesis/energy expenditure

Answer 358

- activates POMC and inhibits NPY/Agrp neurons

Answer 359

- most fat people have high leptin but a lot are leptin resistant

Answer 360

- body fat

Answer 361

o Chronically - reduce body fat o Acutely - if you have a big glucose load, you should suppress having more sugar

Answer 362

- the GI tract - releases over 20 hormones

Answer 363

- causes contraction of the gall bladder

Answer 364

- the hunger hormone

Answer 365

- the stomach

Answer 366

- 28 amino acids long - fatty acid is found on the 3rd amino acid

Answer 367

- ghrelin O-acyltransferase (GOAT)

Answer 368

- increases appetite -\> stimulates Agrp/NPY neurones and inhibits POMC neurones

Answer 369

- L-cells in the distal small intestine

Answer 370

- PYY 3-36 is released post-prandially and is dependent on the size of the meal -\> decreases appetite -\> inhibits NPY release and stimulates POMC - has the opposie effect of ghrelin

Answer 371

- L-cells in the distal small intestine

Answer 372

- a gut hormone (from L-cells) coded for by the pre-propglucagon gene releazed post-prandially - has incretin effects -\> increases insulin levels - reduces food intake

Answer 373

- GLP-1 based drug is important in the treatment of diabetes mellitus - GLP-1 only stimulates glucose-induced insulin release which is good because it means that it only stimulates insulin release when it's needed -\> isn't going to cause hypoglycaemia

Answer 374

- a very short amount of time -\> quickly deactivated by DP-4 - drugs have to be altered so they have a longer half-life

Answer 375

- licensed by FDA and EMEA as a diabetes and obesity treatment

Answer 376

- long-acting GLP-1 receptor agonist (liraglutide) with a tweak structure -\> it is more resistant to degradation which also stops it from being cleared from the circulation giving it a much longer half-life

Answer 377

- there used to be a normal distribution of body weight - ones that were too light will die/not be able to reproduce - ones that were too heavy would get eaten - eventually, we got better at defending against predators and so excess bodyweight became a neutral change

Answer 378

- autoimmune (Type I) diabetes leading to insulin deficiency can present after decades of life -\> this is Latent Autoimmune Diabetes in Adults (LADA) - T2DM can present in childhood (linked to an increasing prevalence of childhood obesity) - people with T2DM can present with diabetic ketoacidosis (though this is more common in T1DM) - monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (e.g. MODY, mitochondrial diabetes) - diabetes can present if someone has a problem with the pancreas -\> e.g. pancreatitis - diabetes can also present in endocrine diseases

Answer 379

o Phaeochromocytoma o Cushing's Syndrome o Acromegaly - all of these cause hyperglycaemia

Answer 380

- various environmental and genetic triggers and regulators which come into play and lead to destruction of beta cells - eventually, auto-antibodies are produced against beta cells -\> patients will then go on to lose their first phase insulin

Answer 381

- C peptide

Answer 382

- over time the beta cells reduce, then stabilise then reduce again -\> a theory suggests that this is due to an imbalance between effector T cells and T-regulatory cells - as time passes the effector T cells increase in number and the T-regulatory cells decrease - much like the mechanism of MS

Answer 383

- increased prevalence of other autoimmune disease -\> most commonly B12 deficiency and coeliac disease as well as others e.g. rheumatoid arthritis, thyroid disease, fertility problems - risk of autoimmunity in relatives

Answer 384

- auto-antibodies can be clinically useful (check the progress of the disease and to confirm the autoimmune basis of the diabetes) - immune modulation offers the possibility of novel treatments

Answer 385

- HLA-DR on chromosome 6 - various DR alleles -\> particularly DR3 and DR4 - DR2 has a protective effect

Answer 386

o two most significant markers - islet cell antibodies (ICA) - group O human pancreas - glutamic acid decarboxylase antibodies (GADA) o other two antibodies: - insulin antibodies (IAA) - insulinoma-associated-2 autoantibodies (IA-2A)-receptor like family

Answer 387

- polyuria - nocturia -\> passing lots of urine at night - polydipsia - blurring of vision - thrush -\> due to increased risk of infections - weight loss - fatigue

Answer 388

- dehydration - cachexia - hyperventilation -\> due to metabolic acidosis -\> try to blow off CO₂ -\> is called Kussmaul breathing - smell of ketones - glycosuria - ketonuria

Answer 389

o insulin has a negative effect on: - hepatic glucose output - protein breakdown in the muscle - glycerol being taken out from the fatty tissue into the periphery o insulin has a positive effect on: - glucose being taken up by the muscle

Answer 390

- lots of glucose goes into the circulation and isn't utilised/taken up by tissues

Answer 391

- catecholamines - cortisol - glucagon - growth hormone

Answer 392

- glucose isn't taken up into cells, due to insulin deficiency, and utilised so a lot of our energy comes from fatty acids -\> lipids in the adipocytes is broken down - normally, you get glycerol coming out of the adipocytes and going to the liver but in the case of insulin deficiency, you get FATTY ACIDS coming out of the adipocytes into the circulation -\> fatty acids then go to the liver where they are converted to ketones (this process is normally inhibited by insulin) o Key Point: as you are deficient in insulin, you get a lot more ketone bodies being produced by the liver

Answer 393

- insulin deficiency - T1DM

Answer 394

- reduce early mortality - avoid acute metabolic decompensation - prevent long-term complications o TYPE 1 DIABETICS REQUIRE EXOGENOUS INSULIN TO PRESERVE LIFE

Answer 395

o Retinopathy o Nephropathy o Neuropathy o Vascular Disease

Answer 396

- reduce calories as FAT - reduce calories as REFINED CARBOHYDRATES - increase calories as COMPLEX CARBOHYDRATES - increase SOLUBLE FIBRE - balance distribution of food over the course of a day with regular meals and snacks

Answer 397

o With Meals - short acting insulin - human insulin - insulin analogues o Background Insulin - 50% of insulin requirement is a basal form - long acting - non-C bound to zinc or protamine - insulin analogues

Answer 398

- provides continuous insulin delivery as well as allowing patients to give dose after eating food (replaces subcutaneous method -\> pre-programmed basal rates and a bolus for meals - does NOT measure blood glucose, so it can't form a feedback loop and completely replace the beta cell function

Answer 399

o Islet Cell Transplants - islet cells are harvested, isolated and injected into the liver - a high risk of rejection, so patients must be on immunosuppressants for life

Answer 400

- capillary monitoring - HbA1c

Answer 401

- capillary glucose levels can be measured by pricking the finger tips -\> is reflective of venous blood glucose but isn’t as accurate - patients can titrate their insulin does based on the capillary glucose reading

Answer 402

- used for long-term blood glucose control is monitored by measuring HbA1c - more glucose that is present in the blood, the more the haemoglobin is glycosylated -\> there is a good correlation between plasma glucose over a reasonably long period of time and HbA1c

Answer 403

- 3 months -\> RBC lifespan is 120 days

Answer 404

- lower risk of complications -\> particularly microvascular complications

Answer 405

- the measurement relies on haemoglobin -\> anything causing an increased turnover of haemoglobin (e.g. haemolytic anaemia or haemoglobinopathy) means the HbA1c may not be accurate

Answer 406

o Main Consequence = HYPERGLYCAEMIA - reduced tissue glucose utilisation - increased hepatic glucose production o METABOLIC ACIDOSIS - circulating acetoacetate and hydroxybutyrate -\> results from increased ketone body production in the liver - osmotic dehydration and poor tissue perfusion -\> hypotension

Answer 407

- no -\> they are inevitable as a result of treating T1DM - is a major source of anxiety in patients and relative

Answer 408

- a plasma glucose \<3.6mmol/L

Answer 409

- any hypoglycaemic event that requires another person to treat it

Answer 410

- \<3mmol/L

Answer 411

- \<2mmol/L

Answer 412

- arrhythmia and sudden death - possible long-term effects on the brain

Answer 413

- loss of warning signs -\> hypoglycaemia unawareness -\> associated with poorly controlled diabetes

Answer 414

o Unaccustomed exercise o Missed meals o Inadequate snacks o Alcohol (if they have too much then they can become unaware of the hypoglycaemia) o Inappropriate insulin regime

Answer 415

o due to increased autonomic activation - palpitations/tachycardia - tremor - sweating - pallor/cold extremities - anxiety o due to imparied CNS function - drowsiness - confusion - altered behaviour - focal neurology - coma

Answer 416

o if the patient is conscious -\> feed the patient - glucose -\> rapidly absorbed as solution or tablet - after some recovery complex carbs -\> maintains blood glucose after initial treatment o if unconsciousnessly impaired -\> parenternal - IV dextrose - 1mg glucagon IM - avoid concentrated solutions if possible

Answer 417

- a fasting blood glucose \> 7 mmol/L

Answer 418

- between 6 and 7 mmol/L -\> between normal and diabetes - has some complications but not those to microvascular

Answer 419

- genetics - intra-uterine environment - adult environment

Answer 420

- autosomal dominant - several hereditary forms - strong family history

Answer 421

- ineffective pancreatic beta cell insulin production - mutations of transcription factor genes and glucokinase genes

Answer 422

- specfic to the the type of MODY -\> solve that problem and therefore help the MODY

Answer 423

- genetics - studies show its almost autosomal dominant - obesity - intra-uterine growth restriction

Answer 424

- diabetes with hyperglycaemia

Answer 425

- dyslipidaemia and stimulation of the mitogenic pathway -\> causes smooth muscle hypertrophy and hypertension -\> macrovascular disease

Answer 426

o we all make less and less insulin as we grow older o at the same time, we become more and more insulin resistant o insulin resistance and insulin secretion lines will intersect -\> beyond this point we won't be able to make enough insulin for our insulin resistance - in caucasians, this intersection normally occurs around 110 years of age, however in other ethnic groups it intersects much sooner

Answer 427

- 1st phase -\> stored insulin is released immediately - 2nd phase -\> over time more insulin is produced and released

Answer 428

- patients developing diabetes will still have some insulin production but they will lose their 1st phase insulin response -\> they can make insulin eventually but it takes a longer time for them to do it -\> can be got around by eating complex carbs which release the glucose more slowly thus reducing the need for a first phase insulin response - over time insulin will stop being made and both 1st and 2nd phase will be lost -\> insulin deficiency sets in

Answer 429

- hepatic glucose output maintains blood glucose at 4 mmol/L

Answer 430

o reduces hepatic glucose output ## Footnote - after eating, insulin stops HGO because you don't need this output from the liver once you've just eaten while driving the glucose into muscle and adipose tissue o both of these effects are absent in T2DM -\> there is insufficient insulin to inhibit hepatic glucose output and insufficient insulin to move glucose into muscle and fat

Answer 431

- adipocytes are full of triglycerides which can be broken down to glycerol and non-esterified fatty acids (NEFA) - insulin would stop this breakdown of triglycerides because there is no need to break down fat stores after you've had a meal -\> glycerol and NEFA travel to the liver - in the liver, glycerol can be used to make glucose - gluconeogenesis and can also be released from the liver via glycogenolysis -\> insulin resistance means that there is increased hepatic glucose output and decreased glucose uptake into tissues - the fatty acids go to the liver, are chopped up into 2-carbon segments and CANNOT be used to make glucose -\> instead used to make very low density lipoprotein triglycerides which are ATHEROGENIC -\> contributes to the atherogenic profile of insulin resistant subjects -\> patients can have atheroma years before high blood glucose

Answer 432

o ischaemic heart disease - breakdown of triglycerides are a particular markers for omental adipocytes

Answer 433

- more than a percipitant -\> fatty acids and adipocytokines are important -\> OBESITY APPEARS TO BE PART OF THE MECHANISM OF T2DM - adipocytokines modulate the insulin resistance - central or omental obesity are the biggest problems - losing wight is a beneficial treatment

Answer 434

- may be important through signalling to the host -\> various lipopolysaccharides are fermented by the gut bacteria to short chain fatty acids -\> can enter the circulation and modulate bile acids and therefore modulate host metabolsim - also appear to be important in inflammation and are involved in adipocytokine pathways - microbiota transplants are being investigated as a treatment for obesity

Answer 435

- weight gain

Answer 436

- metformin

Answer 437

- osmotic symptoms - infections - screening test - upon presentation of a complication -\> acute such as hyperosmolar coma or chronic such as IHD and retinopathy

Answer 438

- education - diet - pharmacological treatment - complication screening

Answer 439

- can help the symptoms of T2DM - reduces the chance of acute metabolic complications - though these are unlikely in T2DM - reduce the chance of long-term complications; good evidence base - education -\> people generally only treat things if they have symptoms so it's important to educate them about the consequences of poor treatment

Answer 440

- control total calories/increase exercise (weight) - reduce refined carbohydrate (less sugar) - increase complex carbohydrate (more rice etc) - reduce fat as proportion of calories (less IR) - increase unsaturated fat as proportion of fat (IHD) - increase soluble fibre (longer to absorb CHO) - address salt (BP risk)

Answer 441

- weight - glycaemia - blood pressure - dyslipidaemia

Answer 442

- metformin -\> used to treat insulin resistance in the liver - orlistat -\> pancreatic lipase inhibitor -\> stops the break down of fat thus restricting fat absorption in the gut - sulphonylureas -\> makes the existing pancreas secrete more insulin - alpha glucosidase inhibitor -\> delays glucose absorption - thiazolidinediones -\> acts on the adipocytes and addresses insulin resistance peripherally in fat and muscle - SGLT2 inhibitors -\> increases glucose excretion by the kidneys

Answer 443

- a biguanide (class of drugs used as oral anti-hyperglycaemic drugs) -\> an insulin sensitiser - used in more or less everyone with T2DM, in particular, overweight patients with T2DM where diet alone has not succeeded

Answer 444

o reduces insulin resistance - reduces hepatic glucose output - increase peripheral glucose disposal o side effects are uncommon but are GI related

Answer 445

- in patients with -\> severe liver failure, severe cardiac failure, mild or worse renal failure

Answer 446

- block the ATP sensitive potassium channel and cause the influx of calcium which leads to INSULIN SECRETION

Answer 447

- is a sulphonylurea and insulin secretagogue

Answer 448

- hypoglycaemia - weight gain -\> therefore preferred in lean suffers of T2DM

Answer 449

- an alpha glucosidase inhibitor

Answer 450

- prolongs the absorption of oligosaccharides -\> allows insulin secretion to cope following the loss of the first phase insulin response - as effective as metformin in early diabetes

Answer 451

- flatulence -\> sugar reaches the large intestine where it is fermented

Answer 452

- pioglitazone

Answer 453

- peroxisome proliferator-activated receptor (PPAR-g) agonists -\> are insulin sensitiser - mainly peripheral -\> improvement in glycaemia and lipids

Answer 454

- peripheral weight gain -\> modification to adipocyte differentiation - older types -\> hepatitis and heart failure

Answer 455

- the modulation of insulin secretion by L-cells in the gut -\> produces products, such as GLP-1, that increases insulin secretion

Answer 456

- GLP-1 - gut hormone produced by L-cells that stimulates insulin secretion (incretin effect) and suppresses glucagon - increases satiety -\> helps with obesity

Answer 457

- it has a short half-life due to degeneration from dipeptidyl peptidase-4 (DPP-4) - gliptins are DPP-4 inhibitors so increase the half-life of GLP-1

Answer 458

- weight - blood pressure -\> 90% of T2DM patients -\> clear benefits - diabetic dyslipidaemia (high cholesterol, triglycerides, HDL-cholesterol) -\> clear benefits to treatment

Answer 459

- intensive lifestyle with good diet and exercise

Answer 460

- retinala rteris -\> diabetic retinopathy - glomerular arterioles -\> nephropathy - vaso vasorum - tiny arteries that supply nerves neuropathy

Answer 461

- severity of hyperglycaemia - hypertension - genetics - hyperglucaemic memory -\> poorly controlled diabetes, even for a short-time, before good controll increase the risk - tissue damage through originally reversible and later irreversible alterations in proteins

Answer 462

- diabetic retinopathy

Answer 463

- optic disc at the nasal part of the eye and the macula more laterally (involved in colour vision and acuity) - various vessels that come out into the back of the retina and they usually have a very regular arrangement

Answer 464

- Background Diabetic Retinopathy - Pre-proliferative Retinopathy - Proliferative Retinopathy - Maculopathy

Answer 465

- hard exudates -\> appear as cheesy, yellow space in the retina -\> due to leakage of lipid content - microaneurysms -\> can rupture and cause blot haemorrhages

Answer 466

- cotton wool spots - aka soft exudates -\> show retinal ischaemia - show severall haemorrhages

Answer 467

- involves the formation of new vessels in response to retinal ischaemia - if the vessels form in the region of the macula they cause problems with acuity and colour vision - the newly formed vessels are generally more fragile -\> can bleed at anytime

Answer 468

- hard exudates near the macula -\> same disease a background diabetic retinopathy barring the location of the hard exudates - can threaten direct vision

Answer 469

- improve control of blood glucose - warn the patient taht the warning signs are present

Answer 470

- pan-retinal photocoagulation -\> laser the retina and therefore stop the vessels bleeding

Answer 471

- pan-retinal photocoagulation -\> laser the retina and stop the vessels from bleeding

Answer 472

- GRID of photocoagulation -\> no need for pan-retinal photocoagulation, can be more targetted

Answer 473

- hypertension - progessively increasing proteinuria - progressively deteriorating kidney function - classic histological features

Answer 474

- cardiovascular events

Answer 475

- mesangial expansion - basement membrane thickening - glomerulosclerosis (hardening of the capillaries) -\> becomes less flexible and harder -\> absorption of nutrients changes -\> more pressure going through the kidneys -\> changes in blood pressure control o essentially, in diabetic nephropathy there is overproduction of matrix leading to mesangial expansion and to basement membrane thickening - as it progresses, you get sclerosis of the glomerulus and secondary effects on the tubulointerstitium -\> several stimuli for these processes including the effects of prolonged exposure to high glucose or glycosylated proteins in at risk patients - rise in the pressure within the glomerular capillaries can stimulate expansion of the matrix -\> angiotensin stimulates pathways that result in overproduction of matrix -\> angiotensin can also cause the constriction of the efferent arterioles, thus increasing transglomerular capillary pressure

Answer 476

- albumin in the urine

Answer 477

- age at development of disease will affect the epidemiology - racial factors - age at presentation - death due to cardiovascular morbidity/macrovascular disease -\> kills them before development of nephropathy

Answer 478

- progressive proteinuria - increased blood pressure - deranged renal function

Answer 479

- urine dipsticks

Answer 480

- normal = \<30mg/24hrs - nephrotic = \>3,000mg/24hrs

Answer 481

- diabetic control - blood pressure control -\> slows down the deterioration in kidney function -\> usually use ACE inhibitors -\> reduce the rate of decline of creatinine thus reducing the rate of deterioration of kidney function - stopping smoking

Answer 482

- diabetes -\> therefore it is the most common cause of amputation

Answer 483

- blockade of the vasa vasorum - small blood vessels which supply the nerves

Answer 484

o Peripheral polyneuropathy o Mononeuropathy o Mononeuritis multiplex o Radiculopathy o Autonomic neuropathy o Diabetic amyotrophy - at Parties, Marilyn Manson Regularly Abuses Drugs

Answer 485

- loss of sensation - loss of ankle jerks - loss of vibrational sense - multiple fractures in the feet -\> can't feel in correct walking -\> can lead to Charcot's joints and permenant damage

Answer 486

- hands and feet -\> longest nerves supply the feet and then the hands

Answer 487

- tall patients - patients with poorly controlled glucose

Answer 488

- monofilament examination

Answer 489

- usually a sudden motor loss - usually in the longest nerves -\> wrist or foot drop - can cause cranial nerve palsy -\> double vision as a consequence

Answer 490

- the loss of motor function in an eye -\> the eye is usually down and out because of the unopposed action of lateral rectus and superior oblique

Answer 491

o pupil sparing third nerve palsy -\> diabetes - pupil responds to light as parasympathetic fibres are on the outside so don't lose blood supply o third nervy palsy caused by aneurysm - pupil is fixed dilated as the aneurysm presses on the parasympathetic fibres first

Answer 492

- a random combination of peripheral nerve lesions

Answer 493

- pain over spinal nerves -\> usually affects the dermatomes on the abdomen and/or chest wall

Answer 494

- autonomic

Answer 495

- loss of sympathetic and parasympathetic nerves to the GI tract, bladder and cardiovascular system

Answer 496

o difficulty swallowing o delayed gastric emptying o constipation/nocturnal diarrhoea

Answer 497

- GI - urinary system - CVS

Answer 498

- bladder dysfunction

Answer 499

- postural hypotension - cardiac autonomic supply -\> cause of sudden death in diabetes patients

Answer 500

o measure changes in heart rate in response to the Valsalva manouevre -\> patients blows into a tube -\> this normally causes a change in heart rate but it doesn’t in diabetics

Answer 501

- a suffers steps on something like a rusty nail and doesnt know it is there for days

Answer 502

- small accumulations of extracellular lipid will lead to atheroma which then leads to fibroatheroma -\> could lead to a complicated lesion which can ulcerate, exposing the fat underneath and this can either thrombose entirely or send emboli further down the circulation - initially, this process begins with accumulation of lipid but progresses to involve smooth muscle -\> this can lead to smooth muscle hypertrophy, fibrosis and calcification

Answer 503

- ischaemic heart disease - cerebrovascular - renal artery stenosis - peripheral vascular disease

Answer 504

o the more insulin resistant you are, the shorter the lifespan

Answer 505

- the same as those who don't have diabetes but have had a MI

Answer 506

- a gender-specific algorithm used to estimate the 10-year cardiovascular risk of an individual

Answer 507

- ischaemic heart disease -\> same mechanism as without diabetes

Answer 508

- earlier with diabetes - more widespread -\> lots of small strokes as well as larger ones

Answer 509

- contributes to diabetic foot problems with neuropathy

Answer 510

- intensive glucose control does improve coronary heart disease risk but not significantly -\> does not translate to much of a change in mortality

Answer 511

- for a given cholesterol, South Asians have an increased risk of CHD mortality

Answer 512

- low birth weight increases the chance of macrovascular disease

Answer 513

- neuropathy - peripheral vascular disease

Answer 514

- the filament bends you have applied 10g of pressure - a normal foot will be able to feel the 10g - normally, the ball of the foot is checked because that is the most common site at which ulcers are found -\> 50% of new foot disease starts at the ball of the foot

Answer 515

- motor neuropathy can cause an imbalance between the extensors and the long plantar flexors causing an abnormal shape in the foot -\> means that increased pressure is being applied on the ball of the foot and the knuckles of the toes

Answer 516

- sugar binding to haemoglobin (HbA1c)

Answer 517

- abnormal blood flow in the foot -\> could cause an increased blood flow at the wrong time so that there is an increase in pulse pressure in the foot - reduced sweating/oil release in the foot which normally protects it from minor disease

Answer 518

- numb - warm and dry - palpable foot pulses - ulcers at points of high pressure -\> ball of the foot

Answer 519

- cold - pulseless - ulcers at the foots margins -\> toes and heel

Answer 520

- numb - cold and dry - pulseless - ulcers at the points of high pressure and the margins of the foot

Answer 521

- diabetics who smoke

Answer 522

- prevent hyperglycaemia - prevent hypertension - prevent dyslipidaemia - stop smoking - education - control diabetes - inspect feet daily - have feet measured when buying shoes - buy shoes with laces and square toe box - inspect inside of shoes for foreign objects attend chiropodist - cut nails straight across - care with heat - never walk barefoot

Answer 523

o relief of pressure -\> bed rest (increases risk of risk of DVT, heel ulceration) so may choose to redistribe the pressurevia a total contact cast o antibiotics -\> possibly long term if it has affected bone o debridement o revascularization -\> angioplasty, arterial bypass surgery o amputation if it is severly infected -\> could be toe, foot or below the knee

Answer 524

- a Charcot's Foot

Answer 525

- bones in the feet don't have their normal articulations due to loss of joint position in diabetes -\> are articulated in such a way that it would be excruciatingly painful in a normal person but in diabetics it is totally painless - abnormal shape of the foot means that there is extreme risk of ulceration

Endocrinology Flashcards

(573 cards)