Endocrinology and Dermatology Flashcards
1
Q
Define Endocrine
A
Pour secretions into blood stream
e.g. thyroid, adrenal and beta cells of pancreas
2
Q
Define Exocrine
A
Glands pour secretions into a duct to the site of action
e.g. pancreas - amylase+lipase
3
Q
Define Endocrine
A
Acts on distant cells
4
Q
Define Paracrine
A
Acting on adjacent cells
5
Q
Define Autocrine
A
Feedback on same cell that secreted the hormone
6
Q
What are 5 ways to control hormone action?
A
- Metabolism
- Receptor induction
- Receptor down regulation
- Synergism e.g. Glucagon + adrenaline
- Antagonism e.g. Glucagon + insulin
7
Q
What is the function of Oxytocin?
A
Milk secretion and uterine contraction
8
Q
What is the function of Theca Cells?
A
Stimulated by LH to produce androgens that diffuse into granulosa cells to be converted into oestrogen.
9
Q
What is the function of Sertoli cells?
A
Sertoli cells produce MIF and inhibin and activin which acts on the pit gland to regulate FSH
10
Q
What is the function of granulosa cells?
A
Granulosa cells are stimulated by FSH to convert androgen’s into oestrogen using aromatase
11
Q
What is the function of Leydig Cells?
A
Stimulated by LH to produce testosterone
12
Q
What does LH act on?
A
In ovaries - Theca cells
In testes - Leydig Cells
13
Q
What does FSH act on?
A
In ovaries - Granulosa cells
In Testes - Sertoli cells
14
Q
What is the LH/FSH axis?
A
Hypothalamus –> GnRH –> AP –> FSH/LH –> Ovaries/testes
15
Q
What does FSH do to granulosa cells?
A
Produces Oestrogen
16
Q
What does FSH do to Sertoli cells?
A
Induces spermatogenesis
17
Q
What does LH do to Theca cells?
A
Produces androgens to diffuse to the granulosa cells to be converted to oestrogen.
18
Q
What does LH do to Leydig Cells?
A
Produce testosterone.
19
Q
What are some characteristics of Water soluble hormones?
A
Unbound and binds to surface receptor, short half-life and fast clearance e.g. peptide (receptors in cell membrane)
20
Q
What are the characteristics of fat soluble hormones?
A
Protein bound and diffuses into cell, long half life and slow clearance e.g. Thyroid hormone + cortisol (receptors in cytoplasm)
21
Q
What is a prolactinoma?
A
A condition where an adenoma causes excess production + release of prolactin.
22
Q
What are 2 causes of prolactinoma?
A
Pituitary adenoma
Anti-dopaminergic drugs
23
Q
What are 5 signs of prolactinoma?
A
Infertility Amenorrhoea Libido loss Visual field effects (bitemporal hemianopia) Headaches.
24
Q
What is the treatment for prolactinoma?
A
Dopamine agonist e.g. Cabergoline
This causes a negative feedback –> promoting dopamine and preventing the release of prolactin.
25
What does prolactin act on?
The mammary glands to produce milk --> + feedback mechanism, breast sucking = less dopamine.
26
What is the mechanism of prolactin release?
Hypothalamus --> dopamine (-) --> AP --> Prolactin
27
What would happen if you block the AP's ability to produce dopamine?
Levels of prolactin would increase.
28
What are the consequences of too much prolactin?
Galactorrhoea
Low libido and testosterone
Infertility
Menstrual irregularity
29
What is acromegaly?
Hormonal disorder resulting from too much GH
30
What is the cause of acromegaly?
Benign adenoma on the pit gland.
31
What comorbidities are seen in Acromegaly?
T2 Diabetes, arthritis, Cerebrovascular events, hypertension + HD, sleep apnoea
32
What are the symptoms of Acromegaly?
- Bigger hands and feet
- Excessive sweating
- Headache
- Tiredness
- Weight gain
- Deep voice
- Amenorrhoea
- Change in appearance
33
What signs might someone with acromegaly present with?
Bi-temporal hemianopia, spade like hands and feet, large tongue, jaw protrusion, interdental separation .
34
What investigations might you do on a patient with suspected acromegaly?
Plasma GH levels can exclude acromegaly
Serum IGF-1 level raised
Oral glucose tolerance test failure of glucose to suppress serum GH and thus IGF-1
MRI of pituitary
35
What is the treatment for acromegaly?
Trans-sphenoidal surgical resection
Radiotherapy
Medical therapy --> dopamine agonists, somatostatin analogues
36
Give an advantage and disadvantage of Trans-sphenoidal surgical resection.
Advantage - Complete removal of the tumour
Disadvantage - many complications are possible e.g. Haemorrhage, CNS injury and hypopituitarism
37
Give an advantage and disadvantage of dopamine agonists in the treatment of acromegaly.
Advantage - no risk of hypopituitarism
| Disadvantage - maybe ineffective.
38
How do dopamine agonists and somatostatin analogues work in the treatment of acromegaly?
They look to control IGF and GH levels.
39
What two drugs can be used to treat acromegaly?
Cabergoline - dopamine agonist
| Octreotide - somatostatin analogue - v effective.
40
What is the main reason for diabetic complications?
Poor glycaemic control
41
What can acute hyperglycaemia cause?
DKA and Hyperosmolar coma
42
What can chronic hyperglycaemia cause?
Micro/macrovascular complications
43
What are 3 microvascular complications of diabetes?
1. Diabetic retinopathy
2. Diabetic nephropathy
3. Diabetic peripheral neuropathy
44
What are 2 macrovascular complications of diabetes?
CV Disease
| Stroke
45
What is the most common type of diabetic neuropathy?
Distal symmetrical polyneuropathy
46
What are 5 signs of autonomic neuropathy?
1. Hypotension
2. HR affected
3. Diarrhoea/constipation
4. Erectile dysfunction
5. Dry skin
6. Incontinence
47
What is a consequence of insensitivity?
Foot ulceration --> failure to heal --> infection and amputation.
48
How is neuropathy distributed?
Glove and stocking - starts at the toes and moves proximally.
49
What are the risk factors for diabetic neuropathy?
1. Poor glycaemic control
2. Hypertension
3. Smoking
4. HbA1c
5. Overweight
6. Long duration of DM
50
What is the treatment for diabetic neuropathy?
- Improve glycaemic control
- Pain relief
- Antidepressants
51
What are the consequences of diabetic neuropathy?
1. Pain - burning and triggered nocturnally
2. Autonomic neuropathy – damage to nerves that supply structures that reg HR, BP, emptying
3. Insensitivity
52
Would you have a decreased or increased pulse in a diabetic neuropathic foot?
Increased.
53
What is diabetic retinopathy?
Complication of diabetes caused by damage to light sensitive tissue in the retina.
54
What is the pathophysiology of diabetic retinopathy?
Micro-aneurysm --> pericyte loss + protein leakage --> occlusion = ischaemia.
55
What are the risk factors for diabetic retinopathy?
1. Long term DM
2. Poor glycaemic control
3. Pregnancy
4. Hypertension
5. High HbA1c
6. Insulin treatment
56
What can diabetic retinopathy be subdivided into?
Proliferation - evidence of neovascularisation
| Nonproliferation
57
What are the 3 stages of diabetic retinopathy?
R1 Retinopathy grade – non-proliferative – interretinal hemorrhages, exudate and micro-aneurysms
R2 Retinopathy grade – Pre proliferative – venous beading, growth of new vessels
R3 Retinopathy grade – Proliferative – new blood vessel on disk
58
What is the treatment of diabetic retinopathy?
People with diabetes are offered regular screening
Laser therapy treats neovascularisation
59
Give 3 signs of acute ischaemia in someone with PVD
1. Pulseless
2. Pale
3. Cold
4. Pain
5. Paralysis
6. Paraesthesia
60
How can you avoid amputation in patients with diabetes?
- Screening for insensitivity
- Education
- MDT Food clinics
- Podiatry
- Revascularisation
- Pressure relieving footwear
61
What is diabetic nephropathy?
Chronic loss of kidney function in those with DM.
62
What is the hallmark of diabetic nephropathy?
Development of proteinuria and progressive decline in renal function.
63
What happens to the glomerular basement membrane in Diabetic nephropathy?
It thickens.
64
How does microalbuminuria present in Type 1 and Type 2 DM?
Type 1 - 5-10 years post diagnosis
| Type 2 - Immediately
65
How can you treat diabetic nephropathy?
```
Glycaemic control
BP Control
ACEi
Cholesterol control
Proteinuria
```
66
What controls serum calcium levels?
The parathyroid.
67
What two hormones does the Parathyroid release to modify calcium levels.
PTH
| Calcitonin
68
When is PTH triggered and what is its action?
Low serum Ca2+ triggers release of PTH --> increases
69
When is Calcitonin triggered and what is its action?
High serum Ca2+ triggers c-cells to release calcitonin
70
What is the action of PTH?
Increases bone resorption
Increases calcium reabsorption at the kidney
Activates vit D --> acts on the intestine to increase calcium absorption
71
What does hyperparathyroidism cause?
Hypercalcaemia
72
What does hypoparathyroidism cause?
Hypocalcaemia
73
What are the causes of hyperparathyroidism?
1. Primary – Parathyroid adenoma PTH and Ca up, phosphate down (Most common)
2. Secondary – Physiological hypertrophy to correct low Ca
3. Tertiary – Renal failure, can’t activate Vit D
4. Prolonged uncorrected hypertrophy
74
What are the symptoms of hyperparathyroidism?
```
Renal/biliary stones
Bone pain
Abdo Pain
Polyuria
Depression, anxiety and malaise
```
Stones, bones, groans, thrones, moans.
75
What is the treatment for hyperparathyroidism?
1. High fluid intake, low calcium diet.
2. Excision of adenoma
3. Correct underlying cause
4. Parathyroidectomy
76
What investigations would you do for hyperparathyroidism?
ECG
| Thyroid function tests
77
What ECG changes would you see in hyperparathyroidism?
Tall T waves
| Short QT waves
78
What is hypercalcaemia?
High serum Ca2+ levels.
79
What are 3 causes of hypercalcaemia?
1. Hyperparathyroidism
2. Hypercalcaemia of malignancy
3. Vit D toxicity
4. Myeloma
80
How could you establish the cause of hypercalcaemia?
PTH test for hyperparathyroidism
81
What are the symptoms of hypercalcaemia?
1. Constipation
2. Vomiting
3. Depression
4. Confusion
5. Increased thirst and frequent urination
82
What is the treatment of hypercalcaemia?
1. IV normal saline
2. Iv Furosemide
3. IV calcitonin
83
What are the symptoms of hypoparathyroidism?
1. Spasm
2. Anxious/irritable
3. Seizures
4. Increased muscle tone
5. Confusion
6. QT prolongation
7. Paraesthesia around lips
8. Tetany and increased reflexes
9. QT elongation
84
What are the causes of hypoparathyroidism?
- AI disease e.g. Addison’s disease
- Injury to Parathyroid gland
- Low blood magnesium levels
85
What ECG changes would you see in hypoparathyroidism?
- Small T waves
| - Long QT interval
86
What is the treatment of hypoparathyroidism?
Calcium supplements
| Resolve underlying cause
87
What is the cause of hypocalcaemia?
1. Dietary insufficiency
2. Anticonvulsant therapy
3. CKD
4. Vit D deficiency
5. Osteomalacia
6. Hypoparathyroidism
88
What are the symptoms of hypocalcaemia?
1. Muscle cramps and spasms
2. Bradycardia
3. Muscle weakness
4. Seizures
5. Facial twitching
89
What is the treatment for hypocalcaemia?
- Calcium supplements
| - Treat underlying cause
90
What metabolic changes are associated with pregnancy?
1. Increased EPO, Cortisol, Nad
2. High CO
3. High Cholesterol + TG
4. Pro thrombotic and inflammatory state
5. Insulin resistance
91
When does the thyroid gland start to develop?
Foetal thyroid follicles and thyroxine synthesis starts at week 10
92
What condition is common in pregnancy?
Hypothyroidism
93
What is the treatment for hypothyroidism?
Levothyroxine
94
Give 5 gestational syndromes
- Pre-eclampsia
- Gestational diabetes
- Obstetric Cholestasis
- Gestational thyrotoxicosis
- Transient Diabetes insipidus
- Postnatal depression
- Postpartum thyroiditis
95
What are some of the complications post pregnancy from untreated hypothyroidism?
1. Gestational hypertension
2. Placental abruption
3. Post-partum haemorrhage
4. Low birth weight
5. Neonatal goitre
6. Pre-eclampsia
7. Risk of miscarriage
96
Why can hCG activate TSH receptors and cause hyperthyroidism?
HCG and TSH are glycoprotein hormones --> very similar structures so hCG can activate TSH receptors
97
Is hypothyroidism or thyrotoxicosis more commin pregnancy?
Hypothyroidism
98
How can you differentiate between grave's disease and gestational thyrotoxicosis?
Graves - symptoms predate pregnancy and get more severe during it --> Goitre + TSH-R antibodies present
Gestational thyrotoxicosis - symtpoms do not predate pregnancy --> No goitre or TSH-R antibodies
99
Consequences of untreated hypothyroidism in pregnancy?
1. Gestational hypertension
2. Placental abruption
3. Post-partum haemorrhage
4. Low birth weight
5. Neonatal goitre
6. Pre-eclampsia
7. Risk of miscarriage
100
Consequences of untreated hyperthyroidism in pregnancy?
Intra-uterine growth restriction
Low birth weight
pre-eclampsia
risk of still birth/miscarriage.
101
What disease is described as a disorder of carb metabolism characteristed by Hyperglycaemia
DM
102
What is the most common cause of hyperthyroidism in Pregnancy?
Graves
103
What is the management for hyperthyroidism?
Carbimazole - can harm foetus so given later
| Propylthiouracil
104
What are the different types of hypothyroidism?
- Primary - Thyroid gland dysfunction
- Secondary – Pituitary (TSH not being made)
- Tertiary – Hypothalamic dysfunction - not making TRH
105
What are 5 causes of hypothyroidism?
AI Thyroiditis e.g. Hashimoto’s
Post-partum thyroiditis
Iatrogenic – thyroidectomy + radioiodine therapy
Drug induced – carbimazole, amiodarone and lithium
Iodine deficiency
106
What are the signs of hypothyroidism?
- Mental slowness
- Bradycardia
- Anaemia
- Loss of eyebrows
- Dry thin hair
- Cold peripheries
- Hypertension
107
What is the management of hypothyroidism?
Levothyroxine
108
What would be the investigations you would order in suspected hypothyroidism?
- TFT – serum TSH high, T4 low
| - Thyroid antibodies --> TPO, TG, TRAb
109
What is thyrotoxicosis?
Excess thyroid hormone production due to any cause
110
What are 5 causes of thyrotoxicosis?
- Increase production e.g. Graves, toxic adenoma
- Leakage of t3/4 due to follicular damage
- Ingestion
- Thyroiditis
- Drug induced
111
What is the pathophysiology of graves disease?
Autoimmune disease - TSH receptor antibodies stimulate thyroid hormone production causing hyperthyroidism.
112
Give 5 symptoms of Grave's disease that doesn/t include opthalmopathy signs
```
weight loss,
increased appetite,
irritable, tremor,
palpitations,
goitre
diarrhoea
malaise
vomiting
muscle spasm
tachycardia, Tachycardia, arrhythmias, heat intolerance
```
113
Give 5 signs of Graves that dont include opthalmopathy signs.
1. Tachycardia
2. Arrythmia e.g. AF
3. Warm peripheries
4. Muscle spasm
5. Pre-tibial myxoedema
6. Thyroid acropach (clubbing and swollen fingers)
114
Give 5 opthalmology signs of Grave's
exophthalmos (bulging eyes), redness, conjunctivitis, pre-orbital oedema, extra-ocular swelling
115
What histology would you see in someone with grave's disease?
lymphocyte infiltration and thyroid follicle destruction
116
What is the treatment for Grave's disease?
Surgery --> partial thyroidectomy
Radioiodine drugs – emit beta particles that destroy thyroid follicles, so TH production goes down.
Ant-thyroid drugs e.g. carbimazole.
117
How does carbimazole work in treating Grave's disease?
Targets TPO so prevents T3/T4 formation.
118
What is a serious side effect of Carbimazole?
Agranulocytosis
119
How do radioiodine drugs treat Grave's disease?
Radioiodine drugs emit B particles that destroy Thyroid follicles so TH production goes down.
120
What are 3 potential complications of a partial thyroidectomy?
hypothyroidism, hypocalcaemia, recurrent laryngeal palsy, bleed
121
How does PTU work in hyperthyroidism?
Preventing the synthesis of new thyroid hormone by stopping T4-->T3
122
What is hyperthyroidism?
An excess of TH
123
What is the mechanisms causing hyperthyroidism?
1. Overproduced thyroid hormone
2. Leakage of preformed hormone from thyroid e.g. Thyroiditis
3. Ingestion of excess TH.
124
What is the cause of hyperthyroidism?
1. Graves’ disease
2. Toxic multinodular goitre
3. Toxic adenoma
4. Thyroiditis
5. Drug induced – Iodine, amiodarone, lithium
125
What can amiodarone cause?
Thyroiditis and leakage
126
What can radiocontrast agents cause?
Temporary hyperthyroidism
127
What are the clinical features of hyperthyroidism?
- Sweating + Heat intolerance
- Anxiety
- Tremor
- Tachycardia
- Weight loss
- Hyperphagia
- Lid Lag + stare
128
What investigations would you order in someone with suspected hyperthyroidism?
Thyroid function test to confirm biochemical hyperthyroidism
Diagnosis of underlying cause is important to treat it
129
What would be the effect on Free T4+3 and TSH in primary hyperthyroidism?
Free t4 + t3 up, suppressed TSH in primary hyperthyroidism
130
What would be the effect on Free T4+3 and TSH in secondary hyperthyroidism?
Free t4 + t3 up, but high TSH due to adenoma in secondary hyperthyroidism
131
What are the 3 thyroid antibodies?
TPO, TG, TRAb
132
What 3 thyroid antibodies would you find in a person with AI thyroid disease?
TPO, TG, TRAb
133
What is the treatment of hyperthyroidism?
- Antithyroid drugs – Carbimazole, propylthiouracil (PTU), methimazole
- Radioiodine
- Surgery (partial or total thyroidectomy)
134
Who is predisposed to thyroid autoimmunity?
Genetic and environmental factors
Women and postpartum is the biggest risk (HLADR3)
Environmental – stress, high iodine intake, smoking
135
What AI diseases are associated with Thyroid autoimmunity?
1. T1DM
2. Addison’s disease
3. Vitiligo
4. Alopecia areata
5. MG
136
What is a goitre?
Palpable and visible thyroid enlargement
137
What are the symptoms of hypothyroidism?
1. Meorrhagia – heavy bleeding
2. Obesity/weight gain
3. Malar flush
4. Tiredness
5. Cold inteolerance
6. Goitre
7. Depression/ poor energy levels/ eyebrow loss
138
What is Conns syndrome?
Primary hyperaldosteronism – high aldosterone independent of RAAS causing increased H20 and sodium retention and potassium excretion.
139
What are the main signs of Conn's syndrome?
1. Hypertension
2. Hypokalaemia
Sodium will be normal or raised
140
What are the main symptoms of Conn's syndrome?
1. Muscle weakness
2. Tiredness
3. Polyuria
4. Hypokalaemia
141
What is the cause of Conn's syndrome?
Adrenal Adenoma
142
What are the hormones involved in Conn's syndrome?
Aldosterone raised – synthesised in zona glomerulosa
Renin is reduced – synthesised by juxta-glomerular cells
143
What investigations would you use to diagnose Conn's syndrome?
1. Bloods – U+E (for renin and aldosterone)
| 2. Plasma aldosterone renin ratio can be used as an initial screening test.
144
What ECG changes would you see in Conn's syndrome?
- Increased amplitude and width of P waves
- Flat T waves
- ST depression
- Prolonged QT interval
- U waves
145
What is the management of Conn's syndrome?
1. Laparoscopic adrenalectomy
| 2. Spironolactone (aldosterone antagonist)
146
What are the constituents of the islets of langerhans?
- Beta cells (70%) – Secrete Insulin
- Alpha Cells (20%) – Secrete Glucagon
- Delta Cells (8%) – secrete somatostatin
- Polypeptide secreting cells (2%)
147
Why are A and B cells close together in the IOL?
To allow them to crosslink
148
What does cortisol inhibit and activate?
Inhibits insulin
| Activates glucagon
149
What is the mechanism of insulin secretion?
Glucose binds to Beta cells --> Glucose-6-phosphate --> ADP --> ATP --> K channels close --> membrane depolarisation --> Ca2+ channels open and influx insulin release
150
What is the physiological response to low blood glucose in a fasting state?
- Glycogenolysis and gluconeogenesis
- Reduced peripheral glucose intake
- Lipolysis and muscle breakdown
- Stimulates release of gluconeogenic precursors
151
What is the physiological response to high blood glucose after feeding?
High blood glucose = high insulin and low glucagon
- Glycogenolysis and gluconeogenesis supressed
- Glucose is taken up by peripheral muscle and fat cells
- Lipolysis and muscle breakdown supressed
3 carbon precursors are needed for gluconeogenesis
152
What are the tests you would order in a patient suspected with diabetes?
Oral glucose tolerance
Random glucose
Fasting glucose
HbA1c
153
What test results would you consider an indicator of DM?
Fasting plasma glucose in diabetes = >7mmol/L
Random plasma glucose in diabetes = >11mmol/L
Oral glucose tolerance test in diabetes = 7mmol/L fasting and >11mmol/L over 2 hours
HbA1c in diabetes = >48mmol/L
154
What is type 1 diabetes mellitus?
A disorder of carb metabolism characterised by hyperglycaemia
155
What is T1DM characteristed by?
Presentation in childhood
| Severe impaired insulin secretion
156
What is the aetiology of type 1 diabetes?
Beta cells express HLA antigens --> AI destruction --> Beta cell loss --> impaired insulin secretion
157
What are the symptoms of T1DM?
- Weight loss
- Thirst (fluid + electrolyte loss)
- Polyuria (osmotic diuresis)
158
What are the two main consequences of T1DM?
Hyperglycaemia and Diabetic ketoacidosis
159
What are the investigations and results for diagnosis in DM?
Fasting plasma glucose in diabetes = >7mmol/L
Random plasma glucose in diabetes = >11mmol/L
Oral glucose tolerance test in diabetes = 7mmol/L fasting and >11mmol/L over 2 hours
HbA1c in diabetes = >48mmol/L
160
What is the treatment/management of T1DM?
- Education
- Healthy diet – low in sugar, high in carbs
- Regular activity and healthy BMI
- BP and Hyperlipidaemia control
- Insulin – injected into SC fat.
161
What is Type 2 diabetes mellitus?
Characterised by both Impaired insulin secretion and insulin resistance
162
What are characteristics of T2DM?
Insulin secretion is impaired due to lipid deposition in pancreatic islets
Hepatic insulin resistance is the driving force of hyperglycaemia in T2DM
DKA rarely seen as insulin levels are still low to prevent muscle catabolism
163
What is the aetiology of T2DM?
Genetic predisposition and environmental factors e.g. obesity and lack of exercise
164
What is the pathophysiology of T2DM?
Impaired insulin secretion and resistance -> IGT --> T2DM --> Hyperglycaemia and high FFA’s
165
What are the risk factors of T2DM?
1. Obesity
2. Physical inactivity
3. Family History
166
What are the symptoms of T2DM?
1. Increased thirst
2. Urination
3. Hunger
4. Unexplained weight loss
5. Ketones in urine
6. Fatigue and irritability
167
What are the investigations and expected results in T2DM?
Fasting plasma glucose in diabetes = >7mmol/L
Random plasma glucose in diabetes = >11mmol/L
Oral glucose tolerance test in diabetes = 7mmol/L fasting and >11mmol/L over 2 hours
HbA1c in diabetes = >48mmol/L
168
What is the management of T2DM?
1. Lifestyle changes --> lose weight, increase exercise, healthy diet
2. Metformin
3. Metformin and sulfonylurea
4. Metformin and sulfonylurea and urea
5. Increased insulin if needed
169
How does metformin work?
By increasing insulin sensitivity and inhibiting glucose production
170
How does Sulfonylurea work?
Stimulates insulin release (can cause hypoglycaemia)
171
Which hormone is insulin antagonistic too?
Glucagon
172
What is the pathophysiological consequence of impaired insulin function?
- Severe glucose deficiency --> glycogenolysis + gluconeogenesis not suppressed, and glucose uptake reduced
- This causes hyperglycaemia and glycosuria
- Perceived stress --> Cortisol and Ad secretion --> catabolic state --> increased plasma ketone
173
What is the pathophysiology of DKA?
No insulin --> lipolysis --> FFA --> oxidised in liver --> Ketone bodies --> ketoacidosis
174
What are 3 examples of Ketones?
Acetoacetate, acetone, beta hydroxybutyrate.
175
Why is DKA only associated with type 1 DM?
Due to severe insulin impairment.
176
Where are FFA oxidised into Ketone bodies?
Liver
177
What are 5 signs of DKA?
1. Hypotension
2. Tachycardia
3. Kussmaul’s respiration
4. Breath smells of ketones
5. Dehydration
178
Give 3 microvascular complications of DM
Diabetic retinopathy
Diabetic nephropathy
Diabetic peripheral neuropathy
179
Macrovascular complications of DM
CV disease
| Stroke
180
What is the main risk factor of complications in DM?
Poor glycaemic control
181
What is a hallmark of Diabetic nephropathy?
Development of proteinuria and progressive decline in renal function
182
What can acute hyperglycaemia induce?
DKA
| Hyperosmolar coma
183
What happens to the GBM in diabetic nephropathy?
Thickens
184
What can Chronic hyperglycaemia induce?
Micro/macrovasc complications
e.g. CV disease, Diabetic nephropathy, DIabetic retinopathy
185
What is the commonest form of diabetic neuropathy?
Distal symmetrical polyneuropathy
186
What is autonomic neuropathy?
Damage to nerves that supply body structures that regulate functions such as BP, HR, Bowel/bladder emptying.
187
In peripheral vascular disease, what are the signs of acute ischaemia?
1. Pulseless
2. Pale
3. Cold
4. Pain
5. Paralysis
6. Paraesthesia
188
What are the major consequences of diabetic neuropathy?
1. Pain
2. Autonomic neuropathy
3. Insensitivity
189
What is the pain associated with diabetic neuropathy like?
1. Burning
2. Paraesthesia
3. Nocturnal exacerbation
190
What are the risks of diabetic complications?
Poor glycaemic control, hypertension, smoking, HbA1c, overweight, long duration of DM
191
What is the treatment for diabetic neuropathy?
- Improve glycaemic control
- Antidepressants
- Pain relief
192
What are the signs of autonomic neuropathy?
1. Hypotension
2. HR affected
3. Diarrhoea/constipation
4. Incontinence
5. Erectile dysfunction
6. Dry skin
193
What are consequences of diabetic insensitivity as a result of diabetic neuropathy?
insensitivity --> foot ulceration --> infection then amputation
194
Describe where insensitivity as a result of diabetic neuropathy starts and how it spreads.
Starts at the toes and moves proximally.
195
How can you prevent amputation in diabetic neuropathy?
1. Screening for insensitivity
2. Education
3. MDT foot clinics
4. Pressure relieving footwear
5. Podiatry
6. Revascularisation and abx
196
What would the pulse be like in a patient with diabetic neuropathy?
Stronger
197
What is the treatment for Diabetic nephropathy?
- Glycaemic and BP control
- ARB/ACEi
- Proteinuria and cholesterol control
198
What are the differences in nephropathy in T1DM and T2DM?
T1DM – Microalbuminuria develops 5-10 years after diagnosis
T2DM – Microalbuminuria is present at diagnosis
199
What are the risk factors of diabetic retinopathy?
Long duration DM, Poor glycaemic control, Hypertension, pregnancy, insulin treatment
200
What is the pathophysiology of Diabetic retinopathy?
Micro-aneurysms --> pericyte loss and protein leakage ---> occlusion --> ischaemia
201
What are the subdivisons of diabetic retinopathy?
1. Proliferative – evidence of neovascularisation in retina
| 2. Non proliferative
202
What are the clinical presentations of Diabetic retinopathies?
1R1 – Non proliferative --> microaneurysms and intraretinal haemorrhages
R2 – Pre-proliferative --> venous beading and growth of new vessels
R3 – Proliferative --> New blood vessel on disc
203
What is the treatment of diabetic retinopathy?
Laser therapy treats neovascularisation.
204
What is Adrenal insufficiency?
Adrenocortical insufficiency resulting in a reduction in mineralocorticoids, glucocorticoids and androgens.
205
Describe the circadian rhythm
- Eye signals to the SCN to sync your body clock.
- This rhythm fine tunes physiology to meet demands of the day and metabolic requirements
- Cortisol should be high when you wake
206
What is the effect of adrenal insufficiency on cortisol and ACTH?
```
ACTH = HIGH
Cortisol = Low
```
207
What is the cause of primary adrenal insufficiency?
- Addison’s disease
- Congenital adrenal hyperplasia
- TB
- Adrenal metastases
- Drugs
- Haemorrhage
- Infection
208
What are the symptoms of adrenal insufficiency?
1. Weight loss
2. Headaches
3. Abdo cramps
4. Myalgia
5. Throwing up
6. Weakness
7. Tired
8. Pigmentation – increased tanning
209
What investigations would you order in adrenal insufficiency?
1. Bloods --> FBC + U, E (Na down K up (due to less aldosterone) CA2+ and urea up
2. Glucose down
3. ACTH stimulation test – Addison’s disease won’t respond
Lack of aldosterone causes less sodium to be reabsorbed and less potassium to be excreted
210
What are the secondary causes of adrenal insufficiency?
- Hypopituitarism
- Withdrawal from steroids
- Infiltration
- Infection
- Radiotherapy
211
What is the treatment for adrenal insufficiency?
Hydrocortisone twice or 3 times Daily to replace cortisol levels 15-25mg
- Primary adrenal insufficiency --> aldosterone treated with fludrocortisone
212
What biochemical investigations could you pursue in adrenal insufficiency?
0900 Cortisol and ACTH
If Cortisol is<100 nmol/l Ai is likely AND over 500 Ai is not likely
If ACTH is over >22 ng/l primary is likely and Less than 5 secondary
Renin is elevated in primary
213
What are features of an adrenal crisis?
- Hypotension
- Fatigue
- Fever
- Hypoglycaemia
- Hyponatremia
- Hyperkalaemia
214
How can you manage an adrenal crisis?
- Immediate hydrocortisone 100mg IV
- Fluid resuscitation 1L N/saline for an hr
- Hydrocortisone 50-100mg IV 6 hourly
- Start fludrocortisone – 100-200ug
215
What are the sick day rules for adrenal insufficiency?
- When ill double dose
- Don’t worry to double dose it wont hurt you in short term
- Carry steroid awareness card
- If vomiting/increasingly unwell 100mg of HC Sub cut
- If cant inject, 20mg and repeat if vomit.
216
What is the treatment in Type 1DM?
1. Education
2. Healthy diet – low in sugar high in carbs
3. Regular activity – healthy BMI
4. BP and hyperlipidaemia control
5. Insulin
217
Where is insulin injected in T1DM and what is a consequence of insulin therapy?
Insulin is injected into SC fat, can also be placed into an insulin pump.
Complications of Insulin therapy – Hypoglycaemia, insulin resistance, weight gain, interreference with lifestyle
218
What is the treatment in T2DM?
1. Lifestyle changes – lose wight, exercise, healthy diet
2. Metformin
3. Metformin + sulfonylurea
4. Metformin +sulfonylurea + Insulin
5. Increase insulin dose as required
219
How does metformin work?
increased insulin sensitivity and inhibits glucose production
220
How does sulfonylurea work?
Stimulates insulin release --> can cause hypoglycaemia
221
How can T2DM be described as?
Impaired insulin secretion and insulin resistance.
222
Describe the portal circulation?
Ant pit has no arterial blood supply, receives blood through a portal venous circulation from hypothalamus
223
What does the anterior pituitary produce?
TSH, FSH, LH, ACTH, Prolactin and GH
224
Where is the anterior pituitary's trilaminar disc derived from?
ectoderm (rathke’s pouch)
225
What does the hypothalamus secrete?
GHRH + SMS, GNRH, CRH, TRH, Dopamine
226
Describe the thyroid axis
Hypothalamus --> TRH --> to AP --> TSH --> Thyroid --> T3 and T4
T3/4 have a negative feedback on hypothalamus and ant pituitary
227
What is Low and high TSH associated with?
- Low TSH = an over-active thyroid
- High TSH – an Overactive thyroid
Underactive thyroid would raise TSH as you have less T3/T4 so no negative feedback
228
Describe the GH/IGF-1 Axis
Hypothalamus --> GNHR (+) or SMS (-) AP --> GH --> Liver --> IGF-1
IGF1 induces cell division. Cartilage and protein synthesis.
229
Describe the HPA axis
Hypothalamus --> CRH --> AP --> ACTH --> Adrenal cortex (zona fasciculata) --> glucocorticoid synthesis (cortisol)
Cortisol has a neg feedback mechanism!
230
What are the functions of cortisol in stress?
1. Mobilises energy sources --> lipolysis, gluconeogenesis
2. Vasoconstriction
3. Supresses inflame + immune responses
4. Inhibits non-essential functions
231
What are some diseases of the pituitary?
- Benign pituitary adenoma
- Craniopharyngioma – common in children
- Trauma
- Apoplexy – bleed causing expansion to local structure
- Sheehan’s – expands during pregnancy, post-partum haemorrhage
- Sarcoid/TB
232
What are consequences of pituitary tumours?
- Pressure on local structures – headaches, visual field defects (bitemporal hemianopia)
- Hypo-pituitary function – pale, obese, no hair.
- Functioning tumour causing Cushing’s, prolactinoma and gigantism
233
Describe the posterior pituitary and it's action.
- Derived from the floor of the ventricles
- Synthesised in the paraventricular and supra-optic nuclei
- Secretes oxytocin and ADH
234
What is the difference between Cushing's syndrome and cushing disease?
Cushing's syndrome refers to a disease of excess cortisol abundance no matter what the cause.
Cushings disease is specific to a pituitary tumour!
235
What is a red flag for cushing's syndrome?
Kid is gaining weight but not growing.
236
What are the causes of cushings syndrome?
- Adrenal tumour (adenoma/carcinoma)
- Pituitary tumour (Cushing’s disease)
- Exogenous steroids
- Ectopic ACTH syndrome
237
What are the symptoms of cushings syndrome?
- Fat - Fat increased and redistributed (central obesity and moon face)
- Protein catabolism – muscle wasting, thin skin and osteoporosis
- Androgenic effects – Acne, hirsutism
238
What are the clinical features of cushings syndrome?
- Carb metabolism – impaired glucose metabolism and diabetes
- Immune suppression
- Central effects – depression, malaise
- Supressed gonadal function – amenorrhoea, loss of libido
- Electrolyte imbalance – sodium retention, hypertension, Hypokalaemia
239
What investigations would you order in suspected cushings syndrome?
- Overnight dexamethasone suppression test – failure to supress cortisol
- Late night salivary cortisol – loss of circadian rhythm
- Urinary free cortisol is raised
- Loss of circadian rhythm
240
What is the treatment for cushings syndrome?
1. Removal of pituitary tumour
| 2. Drugs to inhibit cortisol synthesis --> metyrapone and ketoconazole
241
What investigation could you do to diagnose cushings disease?
- CT scan
- MRI scan
Conducted post diagnosis of Cushing’s syndrome.
242
What is the management of cushings disease?
surgery + radiotherapy
243
What should you do after you have diagnosed cushing's disease?
- If plasma ACTH is >15pg/ml = ACTH dependent syndrome
| - If less ACTH independent Cushing’s syndrome
244
What is the definition of osmolality?
mOsmol/kg --> Measured by an osmometer
Very similar to osmolarity, site of particle isn’t important, but number is
High osmolality = high ADH to reabsorb water.
245
What is the primary cation in ICF?
K
246
What is the primary cation in ECF?
Na
247
What is the primary anion in ECF?
Cl and HCO3
248
What is the function of ADH?
Acts on CD of the nephron to insert aquaporin 2 channels --> H2O retention
249
Describe the release of ADH
- Released when osmoreceptors in hypothalamus detect raised plasma osmolarity
- Post pituitary is signalled to release ADH
- Binds to V2 GPCR
250
What is meant by water deficit?
increased thirst + ADH --> increased water uptake and reduced secretion.
251
What detects the osmolality of a cell?
osmoreceptors
252
What are the signs of SIADH?
1. Anorexia
2. Nausea
3. Malaise
4. Headache
5. Confusion
253
What are the causes of SIADH?
1. Malignancy
2. CNS disorders --> meningitis, brain tumour, cerebral haemorrhage
3. TB
4. Pneumonia
5. Drugs
254
What is the treatment for SIADH?
1. Restrict fluid (Asymptomatic)
2. Give salt (3% saline)
3. Loop diuretics --> furosemide
4. ADH-R antagonists – Vaptans.
255
What is the essential criteria for diagnosing SIADH?
1. Hyponatremia (<135mmol/L)
2. Plasma hypo-osmolality
3. High urine osmolality
4. Clinical euvolemia
5. Increased urinary sodium excretion with normal salt and water intake
256
What diseases should you exclude in SIADH?
1. Renal disease
2. Hypothyroidism
3. Hypocortism
4. Recent diuretic use
257
What are the signs of diabetes insipidus?
1. Excessive urine >3L/24hr
2. Very dilute urine
3. Severe thirst
4. Hypernatremia
5. Dehydration
6. Polyuria
7. Polydipsia – overdrinking
258
What are the investigations of diabetes insipidus?
1. Measure 24-hour urine
2. Test for hyponatremia
3. Water deprivation test – urine will not concentrate when asked not to drink.
259
What is the treatment of diabetes insipidus?
- Desmopressin – in cranial diabetes insipidus
- Hydrochlorothiazide – in nephrogenic DI --> encourages salt + water uptake in Prox tubule.
- Remove the cause
260
What is the cause of polyuria?
1. Hypokalemia
2. Hyperglycaemia
3. Hypercalcemia
4. Diabetes insipidus
261
How is hyponatremia defined as?
Serum sodium 135-144mmol (<135mmol/L is hyponatremia)
| - Mortality much higher if it goes below 125
262
What are the signs of hyponatremia?
- Anorexia
- Confusion
- Headache
- Lethargy
- Weakness
Rapid fall --> Resp arrest, convulsions/ coma
263
What is the treatment for hyponatremia?
- Bolus dose of saline (if dehydration) fluid restriction if not.
- Stop hypotonic fluid
264
What is the investigations in hyponatremia?
- Drug chart
| - Underlining causes --> Bloods etc.
265
What are the causes of hyponatremia?
1. SIADH
2. Sodium Deficiency
3. Renal failure
4. Malignancy
5. Drugs
266
What is Diabetic ketoacidosis?
Absence of insulin and counter reg hormones = hyperglycaemia and rising ketones
267
How can you diagnose diabetic ketoacidosis?
- Metabolic acidosis – plasma bicarb <15mmol/L
- Raised plasma ketones (urine bodies >2+)
- Hyperglycaemia (above <50mmol/L)
268
What is the pathophysiology of ketoacidosis?
No insulin -> lipolysis -> FFA's -> oxidised in liver -> ketone bodies -> ketoacidosis
269
What are the symptoms of diabetic ketoacidosis?
- Hypotension
- Tachycardia
- Dehydration
- Breath smells of ketones
- Kussmaul’s respiration.
270
Which Diabetic condition is Diabetic ketoacidosis seen in?
Mainly T1DM.
Rarely seen in T2DM as insulin is still produced which prevents muscle catabolism and ketogenesis.
271
What are 3 endocrine causes of diabetes?
1. Acromegaly – insulin resistance up,, similar to type 2
2. Cushings -reduced glucose uptake and increased insulin resistance (stimulates new glucose)
3. Pheochromocytoma – increased gluconeogenesis and decreased glucose uptake
272
What is the definition of Puberty?
physiological, morphological and behavioural changes as the gonads switch from infantile to adult forms
273
What is the first sign of puberty in girls?
Menarche
274
What is the Hormone responsible for regulating growth of breast and female genitalia?
Ovarian oestrogen.
275
What is the hormone responsible for controlling growth of pubic and axillary hair in females?
Ovarian and adrenal androgens
276
What is the first sign of puberty in girls?
first ejaculation often nocturnal
277
What is the role of testicular androgens in male puberty?
1. Development of external genitalia
2. Growth of pubic and axillary hair
3. Deepening of voice
278
What is the tanner scale?
used to describe physical development based on external sex characteristics
279
What is thelarche?
breast development --> takes 3 years and is controlled by oestrogen
280
What are the 3 stages of thelarche?
1. Ductal proliferation
2. Adipose deposition
3. Enlargement of areola and nipple
281
What is adrenarche?
Maturation of the adrenal gland --> development of zona reticularis cells
282
What are signs of adrenarche?
- Peri-pubertal adrenal androgen production = mild acne and body odour
283
What is pubarche?
growth of pubic hair
284
What is precocious puberty?
onset of secondary sexual characteristics before 8/9 years old
MUST RULE OUT A BRAIN TUMOUR IN BOYS
285
What is the treatment for precocious puberty?
GnRH super agonist to suppress pulsatility of GnRH secretion
286
What is delayed puberty?
Absence of secondary sexual characteristics by 14/16 yo
287
What is the most common cause of delay in boys?
constitutional delay --> runs late in the family
288
What are 3 consequences of delayed puberty?
1. Psychological problems
2. Reproduction defects
3. Reduced bone mass
289
What must you rule out in girls with delayed puberty and short stature?
Turner's syndrome.
290
What are the functional causes of delayed puberty?
Anorexia, bulimia, over exercising, CKD, Drugs, stress and sickle cell
291
What are the investigations in delayed puberty?
1. FBC – red blood count
2. U+E
3. LH/FSH
4. TFT’s
5. Karyotyping for turners
292
What is Hypergonadotropic hypogonadism?
Primary gonadal failure (Testes or ovarian)
e.g. turners syndrome (45X) Klinefelter’s syndrome (47XXY)
293
What is the effect on hypergonadotropic hypogonadism on FSH/LH and oestrogen and Testosterone.
- High FSH/LH low Oestrogen/Testosterone
294
What is Hypogonadotropic hypogonadism?
Secondary gonadal failure – hypopituitary or problems w/ hypothalamus
295
What is the effect of hypogonadotropic hypogonadism on FSH/LH and oestrogen/testosterone?
- Low FSH/LH and low Testosterone/Oestrogen
| - E.g. Kallman syndrome
296
What is turners syndrome?
missing an x chromosome – 45x. Primary gonadal failure.
Short stature, delayed puberty, CV and renal malformations, recurrent otitis media.
297
What is Kleinfelters syndrome?
patient has an extra X --> 47XXY. Primary gonadal failure.
298
What are 3 symptoms of Kleinfelters syndrome?
- Gynaecomastia, increased risk of breast cancer, testicular size <5ml
- May have azoospermia – semen with no sperm
Symptoms --> Reduced pubic hair, IQ, small testicles and tall stature
- At risk of developing breast cancer
299
What is Kallmans syndrome?
Congenital deficiency of GnRH --> example of secondary gonadal failure
300
What are 2 features of kallmans syndrome?
- 75% cant smell --> ansomia
| - X linked recessive or dominant
