ENDOCRINE Flashcards
(164 cards)
1
Q
modified amino acid hormones
A
adrenaline
thyroid hormones
2
Q
steroid hormones
A
cortisol
progesterone
testosterone
3
Q
peptide hormones
A
ACTH
ADH
oxytocin
4
Q
protein hormones
A
insulin
5
Q
what is autocrine signalling
A
signalling molecules elicit a response in the cell that produced them
6
Q
what is paracrine signalling
A
signalling molecules elicit a response in cells adjacent to the signalling cell
7
Q
what is endocrine signalling
A
signalling molecules elicit a response in distal cells, normally involving travel through the bloodstream
8
Q
examples of hormones with complementary actions
A
adrenaline, cortisol, glucagon, GH, insulin (for growth), IGF-1, sex steroids
9
Q
amine release is mediated by exocytosis dependent on which ion
A
Ca2+
10
Q
how are amines transported
A
‘free’ in plasma (hydrophilic)
11
Q
how are peptide hormones transported
A
‘free’ in plasma (hydrophilic)
12
Q
how are steroid hormones tranpsorted
A
bound to plasma proteins (hydrophobic)
13
Q
what is the role of carrier proteins
A
increase amount of hormone transported in blood
provide a reservoir of hormone
extend the half-lee of the hormone in circulation
14
Q
cortisol is transported in blood bound to which carrier protein
A
cortisol binding globulin
15
Q
thyroxine is transported in blood bound to which carrier protein
A
thyroxine binding globulin
16
Q
testosterone and estradiol are transported in blood bound to which carrier protein
A
sex steroid binding globulin
17
Q
examples of general carrier proteins
A
albumin (steroids, thyroxine)
transthyretin (thyroxine and some steroids)
18
Q
bound hormones can cross the capillary wall to activate receptors in target tissues
true/false
A
false
only free hormone can cross the capillary wall
19
Q
how do carrier proteins prevent abrupt rises in hormone concentration
A
they act as buffers
20
Q
what are the three types of hormone receptor
A
GPCR
receptor kinases
nuclear kinases
21
Q
class 1 nuclear receptors are activated by
A
steroid hormones
22
Q
class 2 nuclear receptors are activated by
A
lipids
23
Q
insulin binds to what type of hormone receptor
A
receptor kinase
24
Q
B cells in the pancreas secrete which hormone
A
insulin
25
a cells in the pancreas secrete which hormone
glucagon
26
delta cells in the pancreas secrete which hormone
somatostatin
27
what is the name of the precursor from which insulin is derived
preproinsulin
28
what is insulin made up of
two polypeptide chain linked by disulphide bonds
29
glucose is transported into B cells brought which transporter
GLUT2 glucose transporter
30
insulin release is mediated by an increase in intracellular concentration of which ion
Ca2+
31
effect of increased ATP in beta cells (glucose metabolism)
inhibits ATP sensitive K+ channels --> depolarisation --> opens Ca2+ channels --> insulin release
32
why is insulin release biphasic?
a small proportion of insulin is immediately available for release, the remainder must undergo preparatory reactions to become mobilised and available for release
33
action of sulphonylureas
inhibit K-ATP transporter, leading to depolarisation of the cell and subsequent release of insulin
34
what is diazoxide used for
stimulate the K-ATP transporter to inhibit insulin secretion in hyperinsulinaemia
35
what is MODY
familial form of early-onset type II diabetes with primary defects in insulin secretion
36
what is the role of glucokinase in MODY2
glucokinase activity is impaired, leading to glucose sensing defect --> increases blood glucose threshold for insulin to be released
37
how does MODY differ from type 1 diabetes
MODY patients normally have some B-cell function available and so can be treated with SUs rather than with insulin
38
stimulatory effects of insulin
```
amino acid uptake in muscle
DNA synthesis
protein synthesis
growth responses
glucose uptake in muscle and adipose tissue
lipogenesis in adipose tissue and liver
glycogen synthesis in liver and muscle
```
39
inhibitory effects of insulin
decreased lipolysis
| decreases gluconeogenesis
40
HbA1c diagnostic of diabetes
48 m/m or above
41
fasting glucose diagnostic of diabetes
7.0 mmol/L or above
42
2-hour glucose in OGTT diagnostic of diabetes
11.1 mmol/L or above
43
random glucose diagnostic of diabetes
11.1 mmol/L or above
44
what is gestational diabetes
any degree of glucose intolerance arising or diagnosed during pregnancy
45
what does HbA1c show
glucose control over the past 2-3 months
46
test which help determine the type of diabetes
GAD/IA2 antibodies
| c-peptide
47
what is the ideal HbA1c range
48-58 mmol/mol
48
what is LADA
late autoimmune diabetes in adults (type of T1DM)
49
insulin is secreted into which vein
portal vein
50
c-peptide levels at diagnosis; type 1 vs type 2
type 1 - low
| type 2 - normal or raised
51
children diagnosed under the age of 6 months are most likely to have which kind of diabetes
monogenic
52
what is Wolfram syndrome (DIDMOAD)
```
diabetes insipidus
diabetes mellitus
optic atrophy
deafness
neurological anomalies
```
53
aims oft therapy in type 1 diabetes
prevent hyperglycaemia
avoid hypoglycaemia
reduce chronic complications
54
rapid acting insulin analogues
humalog (insulin lispro), novorapid, apidra
55
short acting insulin
Humulin S, actrapid, Isnuman rapid
56
intermediate acting insulin
insulatard, Humulin I, Insuman basal
57
long acting insulin analogue
lantus, levemir
58
rapid acting analogue-intermediate mixture
Humalog Mix25/Mix50 or novomix30
59
short acting-intermediate mixture
Humulin M3, Isnuman Comb 15, 25, 50
60
how does a basal bolus insulin regime work
a long acting insulin is administered in the evening, with three rapid acting insulin boluses at meal times
61
how many units of insulin for 10g of carbs
1 unit
62
what is HbA1c a measure of
glycated haemoglobin
63
what is a complication that can arise if injection sites are not rotated in diabetes
lipohypertrophy
64
indications for IV insulin
DKA
hyperosmolar hyperglycaemic state
acute illness
fasting patients who are unable to tolerate oral intake
65
how does metformin help reduce hyperglycaemia
decreases hepatic gluconeogenesis
| increases peripheral glucose uptake
66
how do sulphonylureas help reduce hyperglycaemia
blocks beta-cell K-ATP channel
| increases the 1st and 2nd phase insulin secretion
67
side effects of SUs
weight gain
| hypoglycaemia
68
how do SGLT-2 inhibitors reduce hyperglycaemia
inhibit glucose reabsorption in kidney tubules
69
how do TZDs reduce hyperglycaemia
PPARgamma activator
| increase peripheral glucose uptake
70
side effects of TZDs
increased fracture risk
hepatotoxicity
fluid retention
71
what drug can be used to gain weight loss
orlistat
72
how does orlistat work
inhibits lipases - blocks absorption of dietary fat
73
microvascular complications of diabetes include
IHD
| stroke
74
microvascular complications of diabetes include
neuropathy
nephropathy
retinopathy
75
what are the four types of neuropathy associated with diabetes
peripheral
autonomic
proximal
focal neuropathy
76
how does peripheral neuropathy present in DM
pain/loss of feeling in feet/hands
77
how does autonomic neuropathy present in DM
changes in bowel/bladder function, sexual response, sweating, heart rate, blood pressure
78
how does proximal neuropathy present in DM
pain in the thighs, hips or buttocks leading to weakness in the legs (amyotrophy)
79
how does focal neuropathy present in DM
sudden weakness in one nerve or a group of nerves causing muscle weakness or pain eg carpal tunnel, ulnar mono-neuropathy, foot drop, bells palsy, CN palsy
80
what is Charcot foot
a condition causing weakening of the bones in the pot that can occur in people who have significant nerve damage (neuropathy)
the bones are weak enough to fracture, and with continued walking, the foot eventually changes shape
81
treatment for painful diabetic neuropathy
amitriptyline, duloxetine, gabapentin, pregabalin
| capsaicin cream if cannot tolerate oral treatment
82
how is diabetic neuropathy screened for
foot screening
83
consequences of diabetic nephropathy
development of HTN
decline in renal function
accelerated vascular disease
84
how to screen for diabetic nephropathy
albumin creatinine ratio
85
treatment for diabetic nephropathy
BP maintained <130/80 mmHg
patients with microalbuminuria or proteinuria should be started on an ACEI or ARB
HbA1c maintained <53 mmol/mol
86
what eye pathologies fo people with diabetes get
diabetic retinopathy
early onset cataract
glaucoma
visual blurring due to hyperglycaemia
87
signs of diabetic retinopathy
haemorrhages
cotton wool spots
hard exudates
88
complications of diabetic retinopathy
retinal detachment
| secondary glaucoma
89
how is diabetic retinopathy treated
laser
| vitrectomy
90
what is DKA
a disordered metabolic state that usually occurs in the context of an absolute or relative insulin deficiency accompanied by an increase in the counter-regulatory hormones ie glucagon, adrenaline, cortisol and growth hormone
91
biochemical diagnosis of DKA
ketonaemia >3 mmol/L or significant ketonuria (>2+)
blood glucose >11.0 mmol/L or known diabetes
bicarbonate <15 mmol/L or venous pH <7.3
92
common causes of DKA are
```
infection
intoxication
infarction
ischaemia
insulin missed
```
93
symptoms and signs of DKA
```
thirst/polyuria
dehydration
flushed
vomiting
abdo pain/tenderness
Kussmaul's breathing
ketones on breath
```
94
causes of DKA death adults
hypokalaemia
aspiration pneumonia
ARDS
co-morbidities
95
causes of DKA death children n
cerebral oedema
96
management of DKA
replace fluid (0.9% NaCl then switch to dextrose)
insulin
potassium
manage risk factors (sepsis, aspiration)
97
what is the definition of HHS
hypovolaemia +
hyperglycaemia without significant acidosis or ketonaemia +
hyperosmolar
98
presentation of HHS
older individuals
| high refined CHO intake pre-event
99
management of HHS
cautiously replace fluids and insulin
may require Na
screen of vascular event, sepsis
LMWH unless contraindicated
100
what causes type A lactic acidosis
tissue hypoxaemia
| - infarcted tissue, cariogenic shock, hypovolaemic shock (sepsis, haemorrhage)
101
what cause type B lactic acidosis
liver disease, leukaemia states, diabetes, inherited metabolic conditions
102
presentation of lactic acidosis
hyperventilation
mental confusion
stupor or coma if severe
103
treatment of lactic acidosis
fluids
| antibiotics if appropriate
104
treatment of alcohol induced ketoacidosis
pabrinex (high dose vitamins)
IV fluids
insulin may be required
105
what may cause HbA1c to be reduced
haemolytic anaemia, acute or chronic blood loss, pregnancy
106
immediate treatment of mild hypoglycaemia
15-20 g of glucose or simple carbohydrates
recheck blood glucose after 15 mins
eat a small snack if your next meal is more than an hour away (once BG returns to normal)
107
examples of carbs used in the treatment of hypoglycaemia
glucose tablets
gel tube
2 tbsps of raisins
1/2 cup juice or regular coke
108
treatment of severe hypoglycaemia
glucagon injection
109
what type of drug is metformin
biguanides
110
normal starting dose of metformin
500 mg od or bd
111
does metformin prevent microvascular and microvascular complications
yes
112
GI side effects of metformin
anorexia, nausea, vomiting, diarrhoea, abode pain, taste disturbance
113
dose changes of metformin in renal failure
avoid or stop if eGFR <30 ml/min
| half dose if eGFR 30-35 ml/min
114
metformin and liver toxicity
discontinue if advanced cirrhosis/liver failure, or risk of lactic acidosis (encephalopathy, alcohol excess)
may be beneficial in NAFLD
115
examples of SUs
glicazide
glibenclamide
glimepiride
116
do SUs prevent microvascular and microvascular complications
microvascular - yes
| microvascular - no
117
side effects of SUs
hypoglycaemia, weight gain, GI upset, headache
118
TZD mechanism of action
```
PPARgamma agonist (nuclear receptor)
causes activation of genes that are also activated by insulin
```
119
TZD examples
pioglitazone
120
TZD side effects
hypoglycaemia (with an SU)
increase weight
fluid retention and heart failure
121
do TZDs prevent micro- and macro-vascular complication
no
122
GLP-1 receptor agonists examples
exanatide, expanding, liraglutide, lixisenatide
123
which subunits of K-ATP channel regulate the activity of the channel
SUR1 (SU receptor)
124
where does ATP bind on the K-ATP channel
Kir6.2 subunit
125
which substance binds to the K-ATP channel to close it the extracellular glucose is low
ADP-Mg2+
126
when should SUs be used
first line if intolerant to metformin
| second line if diabetes is not controlled with metformin
127
examples of glinides
repaglinide and nateglinide
128
mechanism of glinides
bind to SUR1 to close the K-ATP channel and trigger insulin release
129
why is insulin response greater to oral glucose than IV glucose
incretin effect
- ingestion of food stimulate GLP-1 and GIP from cells in the small intestine
- they enter the portal blood
- they enhance insulin release and enhance glucose uptake
- GLP-1 decreases glucagon release from pancreas
130
DPP-4 inhibitors are also known as
gliptins
131
mechanism of action DPP-4 inhibitors
inhibit the action of DPP-4 which terminated the action of GLP-1 and GIP
132
side effects of DPP-4 inhibitors
nausea
133
mechanism of action of incretin analogues
mimic action of GLP-1 but last longer due to resistance to DPP-4
134
side effects of incretin analogues
modest weight loss nausea
| pancreatitis (rare)
135
administration of increasingly analogues
SC
136
action of alpha-gluosidase
breaks down starch and disaccharides to absorbable glucose at the brush border in the small intestine
137
action of alpha-glucosidase inhibitors
inhibit the action of alpha-glucosidase therefore preventing the breakdown of complex carbs to glucose
138
side effects of alpha-glucosidase inhibitors
flatulence, loose stools, diarrhoea, abdominal pain, bloating (due to increase population of colonic bacteria)
139
examples of SGLT-2 inhibitors
dapagliflozin, canagliflozin and empagliflozin
140
what is the difference between primary and secondary thyroid disease
primary disease affects the gland itself
| secondary disease is caused by hypothalamic or pituitary disease
141
TSH is also known as
thyrotropin
142
TSH is released by which cells in which aspect of the pituitary
thyrotroph cells in the anterior pituitary
143
biochemical presentation of primary hypothyroidism
low free T3/4
| TSH high
144
biochemical presentation of primary hyperthyroidism
high free T3/4
| low TSH
145
causes of goitrous primary hypothyroidism
```
chronic thyroiditis (Hashimoto's thyroiditis)
iodine deficiency
```
146
causes of non-goitrous primary hypothyroidism
atrophic thyroiditis
147
what is the most common cause of hypothyroidism in the western world
Hashimoto's thyroiditis
148
what antibody is associated with Hashimoto's thyroiditis
thyroid peroxidase (TPO) antibodies
149
microscopic appearance of hashimoto's thyroiditis
T-cell infiltrate and inflammation
150
clinical features of hypothyroidism
```
coarse, sparse hair
dull, expressionless face
periorbital puffiness
pale cool skin that feels doughy to touch
vitiligo
hypercarotenaemia
cold intolerance
pitting oedema
```
151
management of hypothyroidism
levothyroxine
50-100 ug young patients
25-50 ug older patients
152
what is primary hypogonadism (female)
problem with ovaries
| high LH/FSH
153
what is secondary hypogonadism (female)
problem with hypothalamus or pituitary
| low LH/FSH
154
signs of premature ovarian failure
amenorrhoea
oestrogen deficiency
elevated gonadotrophins
155
diagnosis of premature ovarian failure
FSH >30 on two separate occasions
156
what is idiopathic hypogonadotrophic hypogonadism
absent of delayed sexual development associated with inappropriate low levels of gonadotrophin and sex hormone levels in absence of anatomical/functional defects of HPG axis
157
what phenotypic features are associated with idiopathic hypogonadotrophic hypogonadism
anosmia
158
what is the function of kisspeptin
stimulator of GnRH
159
what is Kallman's syndrome
a genetic disorder characterised by loss of GnRH secretion and anosmia/hyposmia
160
in which condition is the absence of olfactory bulbs on MRI
Kallman's syndrome
161
diagnosis of PCOS
2 of;
menstrual irregularity
hyperandrogenism
polycystic ovaries
162
treatment of PCOS
oral contraceptive pill
anti-androgens
local anti-antiandrogens
cosmesis
163
karyptype of turner's syndrome
XO - only one X chromosome
164
signs of turner's syndrome
short stature, webbed neck, shield chest with wide spaced nipples, cubitus valgus, lymphedema
