Endocrinology Flashcards
1
Q
primary hypopituitarism is a problem with the ____ itself
A
gland. eg destruction
2
Q
secondary hypopituitarism is a problem with _____
A
pituitary gland or hypothalamus e.g. tumor
3
Q
in primary hypoadrenalism ___ decreases and __ increases. ___ also decreases
A
cortisol
ACTH
aldosterone
(Primary hypoadrenalism = Addison’s disease)
4
Q
describe secondary hypoadrenalism and its features
A
pituitary tumor damaging corticotrophs
- ACTH low
- cortisol low
- no effect on aldosterone
5
Q
what happens to T4, T3 and TSH in secondary hypothyroidism?
A
all low
6
Q
in primary hypothyroidism what happens to T3, T4 and TSH ?
A
T3 and T4 decrease
TSH increases
7
Q
state 5 causes of hypopituitarism
A
- non-secreting pituitary adenoma
- sheehans syndrome
- pituitary apoplexy
- brain injury
- radiation
- infection, inflammation
- pituitary surgery
- congenital
8
Q
Total loss of anterior and posterior pituitary function
= ?
A
panhypopituitarism
9
Q
What are the results of radiation induced hypopituitarism?
A
GH and gonadotrophins most sensitive - reduction
Prolactin can increase after radiotherapy due to loss of dopamine
10
Q
effect of low FSH/LH?
A
Reduced libido, Secondary amenorrhea, erectile dysfunction, reduced pubic hair
11
Q
effect of low ACTH?
A
Fatigue, weight loss
12
Q
effect of low TSH?
A
fatigue
13
Q
effect of low prolactin?
A
inability to breastfeed
14
Q
effect of low GH?
A
short stature in children
15
Q
post-partum hypopituitarism secondly to blood loss during pregnancy is known as??
A
sheehans syndrome
16
Q
state 4 symptoms of sheehans syndrome and the hormone(s) that cause it
A
- Difficulty breastfeeding or inability to breastfeed - prolactin deficiency
- Failure to resume menses - FSH and LH deficiency
- Cold intolerance - TSH deficiency
- Fatigue - ACTH, TSH and GH deficiency
17
Q
Intro-pituitary hemorrhage of a pituitary Adenoma or less commonly infarction is known as?
A
pituitary apoplexy
18
Q
pituitary apoplexy can be precipitated by __?
A
anticoagulants
19
Q
state 3 key features of pituitary apoplexy
A
- Severe sudden onset headache
- Visual field defect - bitemporal hemianopia
- Cavernous sinus involvement may lead to diplopia and ptosis
(+ low pituitary hormones)
20
Q
how do you diagnose hypopituitarism?
A
- Give insulin injection (insulin stress test) making blood glucose go low. This causes the stress hormones, GH and ACTH to be released.these hormones raise blood glucose. (cortisol measured)
Hypoglycaemia (<2.2mM) = ‘stress’ - Give TRH to stimulate TSH release
- Give GnRH to stimulate FSH and LH release
If the release of hormones in each case is slight or not present = hypopituitarism/problem with the pituitary
21
Q
what is used to replace each hormone in hypopituitarism
A
ACTH - replace with CORTISOL - hydrocortisone or prednisolone
TSH - replace with thyroxine
GH - synthetic GH
cant replace prolactin
FSH & LH - testosterone/ oestrogen + progesterone if no fertility required. if required give FSH and LH instead
22
Q
if unwell/ has fever , what must patients with ACTH deficiency do? why?
A
double steroid dose
patient at risk of an adrenal crisis
23
Q
what is an adrenal crisis? what are the features?
A
low cortisol
- postural hypotension, nausea, weakness
- abdominal pain, hypogylceamia
- can result in collapse/ death
24
Q
Woman with bitemporal hemianopia. Pituitary MRI shows a pituitary tumour. vision. 9AM cortisol 650 nmol/L (>350) fT4 8.1 pmol/L (9-23) TSH 0.2 mU/L (0.3 – 4.2) What is the diagnosis?
A
Low fT4. And low TSH.
= secondary hypothyroidism
25
state 3 differentials for sheehans syndrome
- post-natal depression
- anemia
- Primary Hypothyroidism -after pregnancy effects on immunity - autoimmune disorders may be triggered
26
identify the organum vasculosum & subfornical organ on a diagram of the brain. what do they contain?
osmoreceptors
27
How do osmoreceptors regulate AVP
1. Increase in extracellular Na+
2. Water flows out of osmoreceptor in organum vasculosum and subfornical organ
3. The receptor shrinks leading to receptor firing
4. AVP release from supraoptic nucleus
5. Osmoreceptors also cause thirst
6. Reduced urine volume and plasma conc
28
How does non-osmotic stimulation of vasopressin occur?
Reduction in volume/ Hemorrhage - less stretch - less inhibition of atrial stretch receptors in RA - more AVP release
29
give two reasons why AVP release is good following hemorrhage
- vasocontrictor via V1 receptor
| - helps reasorb water
30
state the symptoms of diabetes insipidus
polyuria, polydipsia, nocturia
31
____ is a condition where there is a lack of vasopressin
CDI
32
state causes of CDI
Pituitary tumour, trauma, autoimmune
33
state the findings you would expect in CDI
Reduction in Vasopressin/ADH
Reduction in urine Osmolality
increase in plasma osmolality - hypernatraemia
34
____ is a condition where there is a lack of response to circulating ADH
nephrogenic DI
35
State causes of NDI
- mutation in V2 receptor
| - lithium
36
state the findings you would expect in NDI
Increase in Vasopressin/ADH
Reduction in urine Osmolality
increase in plasma osmolality - hypernatraemia
37
unlike DI, plasma osmolality is ____ in psychogenic polydipsia
low
38
what goes on the x and y axis in a water deprivation test?
y axis = urine osmolality
| x axis = hours of water deprivation
39
How do we distinguish between cranial and nephrogenic DI?
Give Synthetic vasopressin/ desmopressin/ddAP
| CDI - urine concentrates
40
how does desmopressin work?
| why is it used instead of AVP?
- a selective V2 receptor agonist
| - AVP is unstable, would stimulate V1 receptors in blood vessels, is IV drug
41
drug for NDI?
Hydrochlorothiazide
42
features of SIADH?
- too much ADH
| - reduced urine output
43
state 4 causes of SIADH
1. CNS •Head injury, stroke, tumour,
2. Pulmonary disease - pneumonia, bronchiectasis
3. Ectopic ADH - e.g small cell lung cancer
4. Drugs - carbamazepine, cyclophosphamide, SSRIS
5. Idiopathic
44
how do you treat SIADH?
```
Restrict fluid
vasopressin antagonist (Vaptan)
```
45
what tests should be carried out when you have the following differentials:
- Diabetes mellitus , diabetes insipidus, psychogenic polydipsia,
glucose
sodium levels
random plasma and urine osmolality
water deprivation test
46
State the 5 types of anterior pituitary cells and the result of a functioning pituitary tumor.
```
Somatotrophs - Acromegaly
lactotrophs - prolactinoma
thyrotrophs - TSHoma
gonadotrophs - gonadotrophinoma
corticotrophs - cushings disease
```
47
serum prolactin may be ___ due to a non-functioning pituitary adenoma
raised.
| dopamine cant travel down the stalk
48
serum prolactin may be ___ due to a non-functioning pituitary adenoma because ____
raised.
| dopamine cant travel down the stalk
49
effects of hyperprolactineamia?
- Shut down of GnRH axis (oligo-amenhhorea, low libido, infertility)
- galactorrhoea
50
describe the mechanism by which hyperprolactineamia causes its effects
prolactin binds to kisspeptin neurons in hypothalamus
inhibits kisspeptin release
decrease in GnRH, FSH, LH, T, Oest
51
____ is the most common functioning pituitary adenoma
prolactinoma
52
state 3 pysiological causes of elevated prolactin
Pregnancy/breastfeeding
Stress: exercise, seizure, venepuncture
Nipple/chest wall stimulation
53
Excluding prolactinomas, state 3 pathological causes of elevated prolactin
1. Primary Hypothyroidism - Elevated TRH can increase prolactin
2. Polycystic ovarian syndrome
3. Chronic renal failure
54
____ are an iatrogenic cause of elevated prolactin
antipsychotics (also oestrogens/OCP)
55
How do you determine a “true” elevation in serum prolactin?
no diurnal variation in serum prolactin and no effect from food
56
If a patient has a mild elevation in prolactin, no clinical features consistent with prolactinoma and you have reviewed medication list, what else could be causing elevation?
1. macroprolactin - complex of monomeric prolactin and IgG
| 2. stress of venepuncture- exclude by a cannulated prolactin series.
57
How do you investigate a prolactinoma?
mRI once you’ve ruled out other causes
58
treatment for prolatinoma?
dopamine receptors AGONIST - binds to D2 receptors - CABERGOLINE
59
state 4 features of acromegaly
1. Sweatiness, headache
2. coarsening of facial features
3. increased hand and feet size
4. hypertension
5. impaired glucose tolerance
6. macroglossia
7. obstructive sleep apneoa
60
how do you diagnose acromegaly?
- elevated serum IGF-1
- Oral glucose tolerance test - Failed suppression of GH following oral glucose load
- +ve MRI
- prolactin may be raised due to co-secretion
61
how do you treat acromegaly?
1. first line = surgical- trans-sphenoidal pituitary surgery
2. somatostatin analogues - octreotide
3. dopamine agonists
62
Distinguish between Cushing’s syndrome and Cushing’s disease
Too much cortisol for any reason = Cushing’s syndrome
| Too much cortisol due to corticotroph Adenoma = cushings disease
63
state 2 ACTH independent causes of Cushings syndrome
Taking steroids by mouth (common)
| •Adrenal adenoma or carcinoma
64
How do you investigate someone with Cushing's DISEASE?
First establish cushings syndrome:
- elevated 24 hour urine free cortisol
- elevated late night glucose
- Failure to suppress cortisol after LOW dose oral dexamethasone - increased cortisol secretion
then establish cushings DISEASE
- ACTH will be high
- High does dexamethosone = cortisol suppression
+ve pituitary MRI
65
describe symptoms of hyperthyroidism
- weight loss despite increased appetite
- diarrhoea
- tachycardia, palpitations, tremors and lid lag (sensitised Beta adrenoreceptors)
- heat intolerance
- hypercalceamia (T3 directly stimulates bone resorption)
- pretibial myxedema in graves disease
66
state 3 presentations in a patient with thyroid storm
- delirium
- fever
- tachyarrhythmia (cause of death)
- jaundice (hepatocellular dysfunction)
- cardiac failure
67
thyroid storm is extreme hyperthyroidism. It is hyperthyroidism that worsens in the setting of acute stress such as ___, ____, or _____.
trauma
infection
surgery
68
state 3 causes of primary hyperthyroidism
Graves Disease
Toxic multinodular goiter/ Plummer’s disease
Viral thyroiditis/ de Quervains
69
the most common cause of hyperthyroidism is?
graves disease
70
describe the pathology of graves disease
antibodies bind to TSH Receptor
TSH levels itself are low
- smooth goitre
- pretibial myxeodema
- exophthalamos
71
a thyroid scan in Graves disease will show.....?
smooth iodine uptake
| all black
72
describe the pathophysiology of toxic multinodular goitre
Benign adenoma that is overactive at making thyroxine.
| Tumor grows whist thyroid gland shrinks
73
a thyroid scan in toxic multinodular goitre shows...?
tumor taking up the iodine. not smooth uptake
74
describe the pathophysiology of Viral thyroiditis/ de Quervain
- Virus attacks the thyroid gland
| - Thyroid stops making thyroxine and makes viruses instead
75
state some features of de Quervain
- pain
- dysphagia
- hyperthyroidism followed by hypothyroidism
- pyrexia
76
what would a thyroid scan in de Quervains look like?
- blank
| - no iodine uptake as no thyroxine
77
state 3 different treatments for hyperthyroidism
- thyroidectomy
- radioiodine
- drugs
78
state 3 classes of drugs used to treat hyperthyroidism
- thionamides
- potassium iodide
- beta blockers - e.g. propanolol
79
state 2 thionamide drugs
| what are their mechanisms?
PTU (propylthiouracil) and carbimazole
| Inhibits the enzyme thyroid peroxidase and hence T3 and T4 synthesis
80
what is a key side effect of thionamides?
agranulocytosis
81
state 2 uses of potassium iodide in hyperthyroidism
what is its mechanism
1. Use to prepare patients for surgery - thyroid atrophies and is less vascularized during surgery
2. Use during thyroid storm
inhibits thyroid peroxidase
82
what are the causes of primary adrenal insufficiency?
chronic causes include TB and Addison Disease
83
what are some consequences of adrenocortical failure ?
In primary only:
1. fall in aldosterone - low bp, hyperkalemia, hyponatremia/salt craving, H+ retention an acidosis
2. high ACTH and MSH (skin/mucosal hyperpigmentation)
In primary, secondary and tertiary:
3. fall in cortisol - postural hypotension, abdominal pain, diarrhea, hypoglyceamia, weakness, fatigue
84
what tests are carried out for Addisons and what are the results?
1. 9am cortisol - low OR synthetic ACTH stimulation (failure of cortisol to rise)
2. then follow up with ACTH blood test - high
85
medication for adrenal failure?
fludrocortisone - aldosterone replacement
| hydrocortisone or prednisolone - cortisol replacement
86
most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency.
87
What is the effect of complete 21-hydroxylase deficiency?
high sex hormones - male with precocious puberty, female with virilization.
- low cortisol
- low aldosterone - low bp, hyperkalemia
88
which congenital adrenal hyperplasia is marked by increase in 17-hydroxyprogesterone?
21-hydroxylase deficiency
89
all congenital adrenal hyperplasias are characterised by ___ ____ and ____ adrenal gland _____ due to ACTH stimulation.
```
skin hyperpigmentation (high ACTH, high MSH)
bilateral adrenal gland enlargement
```
90
difference between partial and complete hydroxylase deficiency?
in complete, survival is less than 24 hrs
91
What is the effect of an 11 hydroxylase deficiency?
- low aldosterone
- high 11-deoxycorticosterone -> high bp, hypokalemia
- low cortisol
- high sex hormones (XX virilization, precocious puberty in men)
92
What is the effect of a 17 hydroxylase deficiency?
- high aldosterone -> high bp, hypokalemia
- low cortisol
- low sex hormones -> XY have female type genitalia, XX lack secondary sexual development (primary amenorrhea)
93
state 3 causes of adrenal hyperfunction
1. cushings disease
2. conns syndrome
3. pheochromocytoma
94
state different treatments for cushings syndrome?
depends on cause. primary treatment is surgery
- pituitary surgery
- unilateral adrenalectomy for mass
- medication
- bilateral adrenalectomy
95
what 2 medications are given for cushings syndrome?
| state their functions
Metyrapone - inhibits 11-B hydroxylase
| ketoconazole - inhibits 17-a hydroxylase
96
state 2 side effects of Metyrapone
1. accumulation of 11- deoxycorticosterone - hypertension, hypokalemia
2. Increased production of androgens - hirsutism in women
97
why are metyrapone and ketoconazole used?
to control cushings syndrome before surgery
98
how do you diagnose conn syndrome/primary hyperaldosteronism?
- increase in aldosterone
- decrease in renin
- adrenal adenoma
99
medication for conns syndrome?
spironolactone, epleronone
100
mechanism of spironolactone action?
- blocks Na+ resorption and K+ excretion in the kidney tubules
101
pheos can cause severe ____ hypertension. the high adrenaline can cause death via ___
episodic
| VF
102
treatment for pheaos?
SURGERY.
| pre-operative - alpha blockade + IV fluid, followed by B-blockers
103
lab test results in primary hyperparathyroidism?
- high PTH
- high calcium (or normal)
- low phosphate
104
what is the treatment for primary hyperparathyroidism
parathyroidectomy (as it usually due to adenoma)
105
symptoms in primary hyperparathyroidism?
stones, thrones, bones, groans and psychiatric overtones
osteoporosis - PTH activation of osteoclasts
106
what do lab tests show in secondary hyperparathyroidism?
Due to vitamin D deficiency:
- low Ca2+, low phosphate, high PTH
Due to chronic kidney disease:
- low Ca+, HIGH phosphate, high PTH
- low vitamin D
107
treatment for secondary hyperparathyroidism?
Vitamin D replacement - Give 25 hydroxy vitamin D. D2= ergocalciferol. D3 = cholecalciferol
In patients with renal failure - give 1a hydroxycholecalciferol
108
give the lab values for tertiary hyperparathyroidism. when does this occur?
- Very high PTH
- high calcium
- in the setting of CHRONIC KIDNEY DISEASE
- parathyroid gland autonomously secretes PTH
109
state 4 causes of hypercalceamia
1. primary hyperparathyroidism
2. tertiary hyperparathyroidism
3. bony metastases
4. Vitamin D excess
110
what are the lab values in hypercalceamia caused by metastatic cancer?
- high calcium
| - LOW PTH
111
treatment for hypercalceamia of malignancy?
| describe the mechanism
```
First line = IV fluids
Then bisphosphonates (inhibits osteoclasts)
```
112
infertility is failure to achieve pregnancy after __ months of regular unprotected sexual intercourse
12
113
secondary infertility is?
live birth > 12 months previously
114
What are the causes of infertility and what percentage do they each carry?
30% combined, 30% male, 30% female, 10% unknown
115
state 2 post-testicular causes of male infertility
congenital absence of vas deferens
| erectile dysfunction
116
state 4 pre-testicular causes of male infertility
1. Congenital and acquired endocrinopathies
2. Klinefelters 47 XXY
3. HPG, PRL
117
state 2 ovarian causes of female infertility
anovulation
| corpus luteum insufficiency
118
state 2 cervical causes of female infertility
chronic cervicitis
| immunological
119
treatments for endometriosis?
Hormonal - OCP, prog, Laparoscopic ablation, Hysterectomy
120
what are fibroids?
Benign tumours of the myometrium
121
treatment for fibroids?
Hormonal - OCP, prog, continuous GnRH agonists
| Hysterectomy
122
kallmann syndrome, acquired hypogonadotrophic hypogonadism (low BMI, Excess exercise, stress), and hyperprolactineamia all result in a reduction in ___ in both sexes
GnRH
123
____ is an example of congenital primary hypogonadism in men.
klinefelters
124
____ and ___ are examples of congenital primary hypogonadism in women.
- Turners (45X0)
| - POI (can also be aquired)
125
surgery, trauma, chemo, radiation are all ___ causes of primary hypogonadism in both sexes.
acquired
126
hyperthyroidism and hypothyroidism can cause infertility by reducing bioavailable _____
oestrogen/testosterone
127
what is kallmann syndrome?
| features?
Failure of migration of GnRH neurons into hypothalamus
- low GnRH
- low FSH/LH
- low testosterone/oestrogen
- anosmia
(thus amennorrhea in women,
low sperm count, small testes, cryptorchidism in men)
128
state 4 features of klinefelters syndrome
- small penis and testes
- wide hips
- gynecomastia
- tall with long extremeties
- female hair distribution
- may have mildly impaired IQ
129
Describe the initial history, examination and investigation for Male Infertility
*refer to table in notes*
130
what happens in POI?
Premature atresia of ovarian follicles - Estradiol decreases, LH and FSH increase
131
state 3 causes of POI
1. turners syndrome
2. fragile x
3. cancer therapy
132
What is the most common endocrine disorder and most common cause of infertility in women?
PCOS
133
How do you diagnose PCOS?
Must have two of the following:
1. Oligo or anovulation - anovulation proven using ultrasound or lack of progesterone rise
2. Clinical and or Biochemical Hyperandrogenism.
Clinical - acne, hirsutism, alopecia
Biochemical - raised androgens e.g. testosterone
3. Polycystic ovaries - greater or equal to 20 follicles
134
what causes PCOS?
Hyperinsulinemia or insulin resistance.
This Increases LH:FSH ratio.
Associated with obesity
135
Describe the initial history, examination and investigation for female Infertility
*refer to table in notes*
136
How do you treat PCOS?
To induce regular periods - OCP with progesterone
For fertility - Clomiphene (estradiol receptor antagonist),
Letrozole ( inhibits aromatase in the ovary so it doesnt turn testosterone to oestradiol) Low oestradiol reduces negative feedback on GnRH and pituitary). Increased FSH and LH
Metformin and weight loss
anti-androgens
137
state 4 features of turners syndrome
```
short stature
webbed neck
shield chest
coarctation of the aorta
ovarian dysgenesis
short 4th metacarpals
```
138
how do you induce spermatogenesis?
hCG injections which act on LH receptors. If no response after 6 months, add FSH.
139
Does Congenital Secondary Hypogonadism have better, same or worse prognosis than Acquired Secondary Hypogonadism eg due to a pituitary tumour?
Worse - Congenital Hypogonadotropic Hypogonadism (CHH) eg Kallmann syndrome have not had mini-puberty.
FSH during mini-puberty important for growing the pool of immature spermatogonia and germ cells
140
adverse effects of testosterone replacement?
```
Increased Haematocrit (risk of hyperviscosity and stroke)
Increased PSA
```
141
state the 3 steps in IVF treatment
1. FSH stimulation/ superovulation
2. Prevent premature ovulation
3. LH exposure to mature eggs - hcG to trigger maturation
142
how do you prevent premature ovulation in IVF?
FSH first then later introduce GnRH antagonist in combination = SHORT PROTOCOL
GnRH agonist first then later introduce FSH = LONG PROTOCOL
143
what are some symptoms of OHSS?
Pleural effusion, ascites, renal failure, ovarian torsion
144
Which molecule plays a role in OHSS?
VEGF
145
what does the OCP contain?
oestrogen and progesterone
146
an IUD works by.....?
preventing implantation and sperm egg survival
| copper coil
147
an IUS works by
secreting progesterone e.g. mirena coil
148
state 3 conditions in which you should avoid the OCP
migraine with aura
Diabetes with retinopathy/nephropathy/neuropathy
stroke or CVD history
149
what is HRT used for
relief or prevention of menopausal symptoms
150
HRT increases risk of ____ and there are concerns over _____ risk
endometrial cancer
| cardiovascular
151
_____ ___ is used to treat Prepubertal Young people to stop sexual development?
GnRH agonist
152
a BMI of > than ____ is obese
30
153
state 3 factors affecting obesity
1. screen time
2. poverty
3. education
154
state 3 comorbidities associated with obesity
1. diabetes
2. stroke
3. MI
155
state the 3 types of bariatric surgery
1. sleeve gastrectomy
2. gastric band
3. gastric bypass
156
describe the pathophysiology of Type 1 Diabetes
autoimmune destruction of Beta cells -> partial or complete insulin deficiency
157
___ develops in diabetic patients when their body cant produce enough insulin. It is more common in type 1 but can rarely occur in type 2 also
DKA
158
what happens as you go from early Type 1 diabetes to late
infiltration of immune cells -> they disappear and fibrosis occurs
159
describe the immunology underpinning type 1 DM
1. presentation of auto-antigen to autoreactive
2. CD4+ T lymphocytes
CD4+ cells activate
3. CD8+ T lymphocytes
CD8+ cells travel to islets and lyse beta-cells expressing auto-antigen
4. Exacerbated by release of pro-inflammatory cytokines
160
which type of diabetes is associated with HLA system?
-Type 1 diabetes
- HLA-DR4 and HLA-DR3 carry significant risk.
(4-3) = 1
161
state environmental factors implicated in type 1 DM development
Enteroviral infections
Cows milk protein exposure
Seasonal variation
Changes in microbiota
162
state 2 auto-antibodies found in type 1 diabetes mellitus
- Insulin antibodies (IAA)
- Glutamic acid decarboxylase (GADA)
- d-2 autoantibodies (IA-2A)-- Zinc-transporter 8 (ZnT8)
163
what are the symptoms of T1DM?
Polyuria, nocturia, polydipsia, blurring of vision, recurrent infections, weight loss, fatigue
164
what are some signs of T1DM?
Dehydration, cachexia, hyperventilation, smell of ketones, glycosuria, ketonuria
165
How do you diagnose T1DM?
- Clinical features, HBA1C
- presence of ketones.
- May check for autoantibodies (e.g. GADA, IA2) and c-peptide (should be low)
166
describe some complications of hyperglycemia
acute - DKA
chronic microvascular - nephropathy(renal glomerular arterioles), retinopathy (retinal arteries), neuropathy(vasa nervorum)
chronic macrovascular - IHD, PVD, cerebrovascular disease, renal artery stenosis
167
state 2 types of insulin given with meals/ bolus
| how many times do you give bolus?
- human insulin
- insulin analogues
- 3 times a day after meals
168
state two types of insulin given as basal. how many times do you give basal?
- insulin bound to zinc or protamine
- insulin analogue
- once a day
169
how does insulin pump therapy work?
Continuous delivery of short-acting insulin analogue
Delivery of insulin into subcutaneous space
170
how can transplantation work in type 1 DM?
Islet cell transplant - transplant into hepatic portal vein
Simultaneous pancreas and kidney transplants
171
what are the lab values in DKA?
- increase in H+: pH <7.3,
- HCO3- <15 mmol/L
- ketones increased (urine, capillary blood),
- hyperglycemia: glucose >11 mmol/L
- hyperkalemia
172
what are the symptoms of DKA ?
DKA is D eadly
- delIrium, psychosis
- kussmaul respirations (rapid, deep breathing) - due to metabolic acidosis
- Abdominal (pain, nausea, vomiting)
- dehydration - due to polyuria
- fruity breath odour
173
what is the effect of excess alcohol intake in type 1 diabetes?
hypoglycemia
174
what treatment do you give to a patient with DKA?
IV insulin, IV fluids, and K+ to replete intracellular stores as insulin drives potassium into cells
175
describe some symptoms of hypoglycemia
Sweatiness, palpitations, hungry, tired, shakiness.
Confusion, loss of consciousness if severe
176
describe the pathophysiology of Type 2 DM
insulin resistance + progressive beta-cell failure -> hyperglycemia
177
how do you diagnose T2DM?
Fasting glucose > or equal to 7mmol/L
OGTT > or equal to 11mmol/L
HbA1C > or equal to 48mmol/mol
178
what is the name of the model used to calculate beta cell function using fasting glucose and fasting insulin levels
HOMA model
179
how do you treat type 2 DM
1. oral agents "To Normalize Pancreatic Function" = "gliTs, gliNs, gliPs, gliFs"
2. advanced stage = insulin replacement
180
why do triglyceride levels rise in T2DM?
Insulin promotes the conversion of triglycerides in the blood to NEFA
181
which SNP increases the risk of diabetes the most?
TCF7L2
182
symptoms of T2DM?
Hyperglycaemia, overweight, dyslipidemia, fewer osmotic symptoms. PCOS= risk factor
183
what is a common acute complication of T2DM? and what are its features?
Hyperosmolar hyperglycemic state
184
In diabetes mellitus, what factors are associated with the development of microvascular complications?
High BP - most important
higher HBA1C
genetics
hyperglyceamic memory
185
what are the stages of retinopathy?
| describe the findings in each stage
1. Background Retinopathy - hard exudates (cheese spots) + blot hemorrhages
2. pre-proliferative retinopathy - soft exudates/cotton wool spots. represent retinal ischemia
3. proliferative retinopathy - visible new vessel s
186
__ can occur at any stage of retinopathy. It is characterised by hard exudates near the ___. This can threaten direct vision
maculopathy
| macula
187
on a picture of a normal retina, label the fovea (macula) and optic disc
check notes
188
how is retinopathy treated?
1. All types require improvement in HBA1C and better blood pressure control
2. Pre-proliferative and proliferative require panretinal photocoagulation
3. Maculopathy requires anti-VEGF injections for oedema and Grid photocoagulation
189
what are the characteristics of diabetic nephropathy?
Decline in eGFR
urine albumin:creatinine ratio, >2.5 in men, >3.5 women shows microalbuminuria. ACR> 30 = proteinuria
advanced = peripheral oedema
190
how do you treat diabetic nephropathy?
HBA1C and blood pressure management, stop smoking
ACE inhibitors (cause dilation of efferent arteriole and reduce hyperfiltration)
191
what is the most common type of neuropathy
Peripheral sensory neuropathy
- Others include mononeuritis multiplex and autonomic neuropathy
- Or mononeuropathy- sudden motor loss, wrist drop, foot drop, cranial nerve palsy - double vision due to 3rd
192
what factors contribute to macro vascular complications in diabetes
1. dyslipedemia - most important
2. high HBA1C
3. hypertension
4. central fat
193
how do you assess neuropathy?
vibration, temp, fine touch sensation
| ankle jerk reflex
194
state and describe the different types of foot ulcers
Neuropathic foot - numb, warm, dry, ulcers at points of high pressure loading, palpable pulse
Ischaemic foot - cold, pulseless, ulcers at the foot margins
Neuroischaemic - numb, cold, dry, pulseless, ulcers at p high pressure and margins
195
__ ___ are hyperpigmented plaques in intertriginous sites often associated with insulin ___. It is also rarely associated with malignancy
acanthosis nigricans
| resistance
196
state two mechanisms that lead to chronic complications in Diabetes mellitus
1. non-enzymatic glycation and AGEs
| 2. Sorbitol accumulation
197
State the actions and side effects of metformin
Activates AMPK in hepatocyte mitochondria -> inhibits ATP production -> blocks gluconeogenesis
Also blocks adenylate Cyclase -> promotes fat oxidation
Reduced hepatic glucose output
Increases insulin sensitivity,
GI side effects - contraindicated in liver, cardiac or renal failure
SEs: Lactic acidosis, weight loss
198
State the actions and side effects of Glitazones/thiazolidinediones
E.g. pioglitazone
PPAR-gamma receptor agonist
Increases insulin sensitivity and levels of adiponectin -> Regulation of glucose metabolism and fatty acid storage
weight gain but it is mainly peripheral, heart failure, MI
199
State the actions and side effects of Sulphonylureas
E.g. gliclazide
Close K+ channels in pancreatic B cell - depolarization - insulin release
SEs: weight gain, hypoglycemia
200
State the actions and side effects of DPP-4 inhibitors
Gliptins group of drugs
Increases glucose-induced insulin secretion
Inhibits DDP4 enzyme in vascular endothelium tthat deactivates GLP-1
GLP1 can exert its effects
Satiety, URTIs, UTIs
201
State the actions and side effects of SGLT-2 inhibitors
“Glifs” group of drugs - e.g canagliflozin
Decreases glucose absorption - blocks reabsorption in PCT
Glycosuria - UTIs
202
How does metformin move across body compartments?
via OCT1
203
what does the "To Normalize Pancreatic Function"
| mnemonic mean?
gliTs - thiazolinodionses/glitazones
gliNs - meglitinides
gliPs - DDP4 inhibitors
gliFs - SGLT-2 inhibitors
204
What is POI also known as?
| What would lab results look like?
Acquired primary hypogonadism
| Low oestradiol, high FSH and LH
205
How do you treat POI?
IVF
Egg donation
Blood test for AMH - marker of ovarian reserve
206
DKA is typically associated with which type of diabetes mellitus?
Type 1
207
State the actions and side effects of GLP1 analogs
e.g Liraglutide
Responsible for incretin effect
Increase glucose induced insulin secretion
Inhibits glucagon and delays gastric emptying
