1
Q
Describe three hormonal responses to exercise
A
- Glucagon releases sugar from stored glycogen and stimulated gluconeogenesis
- Cortisol enhances the metabolic utility of glucose
- Adrenaline helps to pump leaked K back into the cell via the Na/K pump as there is a tendency for K concentration to increase in the blood during exercise
2
Q
How do steroid hormones leave the cell?
A
Simple diffusion
3
Q
Describe the steps in insulin secretion
A
- Beta cell imports glucose by facilitated diffusion by GLUT2
- Glucose is transformed to glucose-6-phosphate by glucokinase
- This yields ATP, which binds to the Kir6.2 subunit of the KATP channel
- This causes the channel to close, which depolarises the membrane
- This causes voltage gated Ca channels to open and so insulin is released
4
Q
How are ATP, ADP and Mg related to the KATP?
A
ATP binds to the Kir6.2 subunit to close the channel
ADP+Mg binds to the SUR1 subunit to open the channel
5
Q
Give at least one example of each of the following insulins:
- Rapid acting analogue
- Short acting
- Intermediate acting
- Long acting analogue
- Rapid acting analogue-intermediate mixture
- Short acting-intermediate mixture
A
- Rapid acting analogue: Humalog, NovoRapid
- Short acting: Humulin S, ActRapid
- Intermediate acting: Humilin I, insulatard
- Long acting analogue: Lantus, Levemir
- Rapid acting analogue-intermediate mixture: Humalog Mix25
- Short acting-intermediate mixture: Humulin M3
6
Q
What are target blood sugars pre meal and 1-2 hours after beginning a meal?
A
Pre meal: 4-7
1-2h after beginning: <10
7
Q
How many units of insulin should you start a patient on?
A
0.3 units per kg body weight for the whole day
8
Q
How many units of insulin should you add per CHO?
A
1 unit per 10g CHO
9
Q
What should a diabetic patient’s blood sugar be before going to bed?
A
8
10
Q
When should you not use Metformin?
A
Renal impairment with eGFR <40 or creatinine >150
11
Q
When should you stop Metformin?
A
Pre-operatively or in severe illness - risk of lactic acidosis
12
Q
Aside from effects in insulin + glucose, what else does Metformin do?
A
Decreases triclycerides
Decreases BP
13
Q
TZDs
- Side effect
- Contraindication
- Prevent micro or macrovascular complications?
A
- 3-4 kg weight gain due to increased fat mass and fluid retention
- heart failure - because of fluid retention
- prevent macrovascular complications
14
Q
Do SUs prevent micro or macrovascular complications?
A
Microvascular
15
Q
Main side effect of Acarbose?
A
Diarrhoea and flatulence
16
Q
What should an annual review of diabetes include?
A
Weight Blood pressure Bloods: HbA1c, renal function, lipids Retinal screening Foot risk assessment Record severe hypoglycaemia episodes of admission with DKA
17
Q
Give some examples of autonomic neuropathy
A
Resting tachycardia Urinary infrequency Erectile dysfunction Hypoglycaemic unawareness Delayed gastric emptying Dry foot
18
Q
What is proximal neuropathy in diabetes?
A
Dermatomal distribution of a single neuron e.g. pain in the thighs, buttocks or legs, leading to profound muscle wasting
19
Q
What is focal neuropathy in diabetes?
A
Sudden weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel, ulnar neuropathy, foot drop
20
Q
What are normal urinary creatinine albumin ratios in men and women?
A
Men <2.5 mg/mmol creatinine
Female <3.5 mg/mmol creatinine
21
Q
Treatment of Charcot’s foot?
A
Cast
22
Q
What are the following in DKA:
- Creatinine
- Sodium
- Amylase
- WCC
- BP
A
Creatinine if often raised
Sodium is often reduced
Amylase is frequently raised - doesn’t necessarily mean pancreatitis
WCC is often raised - doesn’t necessarily mean infection
BP is reduced
23
Q
What is the insulin regimen for DKA?
A
Fixed rate intravenous insulin infusion
Also give IV 0.9% NaCl
If hypotensive give bolus of 500 mls normal saline
Even if hypotension is resolved, patient still needs large volumes of fluid
24
Q
What is potassium like in DKA and how should you treat it?
A
Likely will need to replace it - add KCl to bags of fluid
Initially patient is hyperkalaemic - because insulin is required to drive K into the cells
Titrate potassium to hourly VBG
K >5.5 - don’t replace
K 3.5-5.5 - replace by using 40 mmol infused solution
K <3.5 - seek senior help
25
What other investigations should you do in DKA?
Often infection with no fever, so do MSU, blood cultures, CXR
Start broad spec antibiotics early if infection is suspected
26
Give two causes of hyperkalaemia in DKA
The patient is in acidosis, so there is increased H+ - this is then driven into the cell at the expensive of K+
Insulin is required for uptake of K into cells
27
What is the classic triad in HHS?
Hypovolaemia
Hyperglycaemia
Hyperosmolar
28
Name two precipitants of HHS
Glucocorticoids
Thiazide diuretics
Also MI, bowel infarct
29
Give two precipitants of LA
Metformin
| Septicaemia
30
What is lactate?
End product of anaerobic metabolism of glucose
31
What are the two types of LA?
Type A - associated with hypoxia
| Type B - associated with liver disease
32
Lab findings of LA?
Raised anion gap
| Decreased bicarbonate
33
Age of onset of MODY
Before 25
| Also strong FHx
34
What are the clinical differences between the two types of MODY?
Glucokinase type - onset at birth, stable hyperglycaemia
| Transcription factors type - onset in teenage years, progressive hyperglycaemia
35
What is LADA also called?
| What does the presentation mimic?
Aka slowly progressive type I
"Typical" type II diabetes, but tend to not be overweight
Also autoantibody positive
36
Name an enzyme that insulin inhibits
Glycogen phosphorylase - i.e. inhibits degradation of glycogen to glucose
37
Describe the synthesis of insulin
Formed from preproinsulin - cleaved to proinsulin in the ER
Proinsulin contains A and B subunits, linked by C
C peptide is cleaved off of proinsulin at the Golgi apparatus
A and B are now bound by disulphide bonds
This structure is insulin
38
The insulin receptor is what type of receptor?
Tyrosine kinase receptor
39
What does the insulin receptor consist of?
Two alpha subunits
Two beta subunits
Two tyrosine kinase - enzyme which is active when phosphorylated
40
Describe activation of the insulin receptor
Two insulins bind to the alpha subunits
This causes tyrosine kinase to phosphorylate the target protein (called IRS-1)
IRS-1 then exerts the intracellular effects of insulin
41
Give seven functions of thyroid hormone
1. Increases basal metabolic rate
2. Increases thermogenesis
3. Increases insulin-independent glucose uptake into cells
4. Increases fatty acid oxidation in tissues
5. Increases protein synthesis
6. GHrH production + secretion requires thyroid hormones
7. Permissive sympathomimetric action - increases responsiveness to adrenaline and sympathetic NS
42
What are the types of deiondinase enzymes and what are their uses?
Important in de/activation of thyroid hormone
D1 - commonly found in liver and kidney
D2 - found in the tissues - main one concerned in interplay between T3 and T4
D3 - found in foetal tissue + placenta + brain
43
How do carbimazole and propylthiouracil work?
Inhibit attachment of iodine to thyroglobulin
44
Treatment of hypothyroidism?
Must gradually restore metabolic rate, or patient will get arrhytmias
Younger - thyroxine 50-100 ug daily
Older - thyroxine 25-50 ug daily
45
What is DeQuervains thyroiditis?
Aka subacute thyroiditis
Vital trigger, usually self limiting after a few months
Initially have hyperthyroidism, then hypothyroidism, then back to normal
46
What does differentiated thyroid cancer refer to?
| Why is the word "differentiated" important?
Papillary and follicular
Differentiated - two reasons
- Looks like normal thyroid cells
- Vast majority take up iodine and secrete thyroglobulin
47
What is Medullary thyroid cancer associated with?
MEN2
48
What is seen on histology of medullary thyroid cancer?
Amyloid deposition
49
What is the most serious type of thyroid cancer?
Anaplastic - causes rapid growth, involvement of neck structures and death
50
How is cytology of thyroid cancer graded?
| What are follicular lesions graded at?
```
Thy 1 - insufficient/uninterpretable
Thy 2 - benign
Th 3 - atypia, probably benign/equivocal
Thy 4 - atypia suspicious of malignancy
Thy 5 - malignant
Follicular lesions are Thy 3
```
51
What does AMES stand for?
Age
Metastases
Extent of primary tumour
Size of primary tumour
52
What is Tayside lymph node removal policy in papillary thyroid cancer?
Central compartment clearance and lateral node sampling
53
When and how is whole body iodine scanning done?
```
After surgery
Monday - rhTSH IM injection
Tuesday - rhTSH IM injection
TSH should be greater than 20 for best results
Wednesday - give the capsule
Friday - scan
```
54
How should you treat a patient after thyroid remnant ablation?
Suppress TSH with thyroxine - improved prognosis if suppressed TSH in the long term
55
What can be used as a tumour marker post thyroid ablation?
| What can throw this reading of?
Thyroglobulin
| Antibodies to thyroglobulin can throw it off - scan these patients every 6 months
56
Important risk of thyroid remnant ablation?
Small but significant increased risk of leukaemia
57
What does a primary follicle contain and what is the purpose of the contents?
Contains an oocyte surrounded by granulosa cells and theca cells
Theca cells produce androgens, which are converted to estrogens by the granulosa cells via the enzyme aromatase
58
What happens to the corpus luteum after ovulation?
It is left behind in the ovary and starts to secrete progesterone
59
Give to functions of progesterone
Causes the endometrium to thicken
| Inhibits FSH and LH
60
What is the role of androgens and diabetes in PCOS?
Hyperinsulinaemia causes an increase in androgens in the body
The rise in insulin drives thecal cells of the follicle to produce more androgens
The granulosa cells convert this to excess estrogen
High levels of estrogen and androgens cause a disordered release of LH and FSH
61
What is the role of estradiol in the negative feedback loop?
Low concentrations of estradiol inhibit the release of FSH
| High estradiol has a positive feedback on the pituitary to stimulate LH release
62
Where are Leydig cells found?
Where are Sertori cells found?
What else is found here?
Leydig - interstitium of the seminiferous tubules
Sertori - seminiferous tubules
Also in the seminiferous tubules are spermtogonia - male germ cells with the ability to become sperm
63
What is the role of Leydig cells?
LH targets Leydig cells and causes them to secrete testosterone
64
What is the role of Sertoli cells?
Tertosterone produced by Leydig cells stimulates Sertoli cells to maintain libido, maintain muscle + bone growth, maintain male secondary sexual characteristic
FSH stimulates Sertoli cells to release androgen binding protein
65
What all do Sertoli cells need for stimulation?
Presence of testosterone
| Stimulation from FSH
66
What is the role of ABP in the male reproductive system?
ABP binds to androgen in the seminiferous tubule to promote sperm growth aka spermatogenesis and spermiogenesis
67
Which two things are required for sperm production?
ABP and testosterone
68
What role do Sertoli cells have in the negative feedback loop?
Release inhibin - inhibits the secretion of FSH in order to regulate sperm production
69
What is the difference between the size of the gametes in spermatogenesis compared to oogenesis?
Sperm are smaller than spermatocytes
| Ova are larger than oocytes
70
What is the difference in onset between spermatogenesis and oogenesis?
Spermatogenesis begins at puberty
| Oogenesis begins in the foetus (pre-natal)
71
How long does spermatogenesis take?
65-75 days in the human male
72
In spermatogenesis, where do meiosis and mitosis occur?
Meiosis inside the cell
| Mitosis outside
73
At birth, what does each follicle contain?
A dormant primary oocyte - a diploid cell that is resting in prophase of meiosis I
74
What happens to the follicles after puberty?
Every 28 days, FSH from the pituitary stimulates one of the dormant follicles to develop
The primary oocyte then completes meiosis I and starts meiosis II
75
What is the role of LH in oogenesis?
It halts the egg at metaphase II, to allow cytoplasmic maturation
When fertilized, completion of meiosis occurs
76
Which hormones are responsible for the fertile and infertile cervical mucus?
Estrogen - fertile cervical mucus
| Progesterone - infertile (thick) cervical mucus
77
Describe the clinical features of Rubella syndrome
```
Rash at birth
Low birth weight
Small head size
Heart abnormalities
Visual problems
Bulging fontanelle
```
78
How can you confirm ovulation?
Midluteal (D21) serum progesterone - >30 nmol/l in two samples
79
What are hormone profiles like in WHO ovulatory disorder II?
Normal gonadotrophs/excess LH
Normal estradiol
Low progesterone
Raised testosterone (in PCOS)
80
When in the cycle is clomid given?
Day 2-6 (i.e. for 5 days)
| NB - cumulative conception rate plateus at 12 months on this drug
81
Treatment of hyperprolactinaemia?
Dopamine agonist - Cabergoline, Bromocriptine
82
In which ovulatory disorders in estradiol low?
WHO type I
| WHO type III
83
Treatment of premature ovarian failure?
Hormone replacement with estrogen
| Egg or embryo donation
84
Dysmenorrhoea (before menstruation) + dyspareunia + menorrhagia + painful defaecation + chronic pelvic pain = ?
Endometriosis
85
How would you investigate tubal disease in women?
If no known risk factors - hysterosalpingogram
| Laparoscopy if known or suspected tubular pathology from suspicious history
86
List some causes of functional hypothalamic amenorrhoea
```
Weight change
Stress
Exercise
Anabolic steroids
Iatrogenic - surgery, radiotherapy
Recreational drugs
Head trauma
Infiltrative disorders e.g. sarcoidosis
```
87
What is the gold standard test for pituitary function?
Insulin stress test
You give someone insulin to make them go hypo - stimulated the hypothalamus
Normal response is for cortisol and GH to rise significantly
88
What happens in the water depravation test?
Give patient no water for 8 hours to try and stimulate ADH production
Can't measure ADH directly, so measure the concentration of the urine
89
What is the most common cause of Cushing's syndrome?
Exogenous steroid use
90
What is Cushing's disease?
Bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma
91
What are some clinical features of ACTH-dependent Cushing's?
```
Skin pigmentation
Hypokalaemic metabolic acidosis
Weight loss
Hyperglycaemia
Classic features of Cushings are often absent
```
92
When is an overnight dexamethasone suppression test positive?
if > 50
93
Describe the meaning of the results in a high dose dexamethasone suppression test
If ACTH still high then problem is adrenal of SCLC
| If ACTH is suppressed by 50% or more then pituitary adenoma
94
What other physiology should you consider in Cushings, aside from cortisol?
Zona reticularis is also controlled by ACTH - if Cushing's is caused by high ACTH, then ZR will be affected
This produces large amounts of testosterone in the body
95
Give two common causes of hypokalaemia
Hyperaldosteronism
| Bartter's syndrome
96
What is barter's syndrome?
Defect in Loop of Henle
| Bloods show hypokalaemia
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