Endocrinology Flashcards
1
Q
What is the difference between endocrine and exocrine?
A
endocrine secretions go into the bloodstream
exocrine secretions go through a duct to the site of action
2
Q
What is the endocrine action of a hormone?
A
blood-borne, acts on a distant site
3
Q
What is the paracrine action for a hormone?
A
Acts on nearby or adjacent cells
4
Q
What is the autocrine action of a hormone?
A
Feeds back on the same cell that secreted the hormone (itself)
5
Q
Give some features of water-soluble hormones
A
Unbound
Fast clearance
Bind to surface receptors on cells
Short half-life
6
Q
Give some features of fat-soluble hormones
A
protein-bound
slow clearance
diffuse into cells
long half life
7
Q
What are the four classes of hormones?
A
Peptides
Amines
Iodothyronines
Steroids and cholesterol derivatives
8
Q
Describe peptide hormones. Give an example
A
Water soluble
stored in secretory granules
cleared by tissue or circulating enzymes
synthesis is from a pre-hormone to a prohormone
packaging is a prohormone to a hormone and then stored as a hormone
e.g. insulin
9
Q
Describe amine hormones. Give an example
A
e.g. dopamine, adrenaline, noradrenaline
Phenylalanine -> L-Tyrosine -> L-dopa -> dopamine -> noradrenaline -> adrenaline
10
Q
How can adrenaline and noradrenaline be measured in serum?
A
Noradrenaline and adrenaline are broken down to COMT to normetanephrine and metanephrine
These can be measured in serum
11
Q
Describe iodothyronines and give an example
A
e.g. thyroxine, tri-iodothyronine
Fat-soluble
Iodothyronines produce T3 and T4 through conjugation
most are T3/tri-iodothyronine which is more active
T3 is converted to T4/thyroxine
12
Q
Describe steroids and cholesterol derivatives and give and example
A
e.g. Vitamin D
fat-soluble
directly binds to nucleus to stimulate mRNA production
transported by Vitamin D binding protein
e.g. adrenocortical and gonadal steroids
fat-soluble
passes to nucleus to induce a response
altered to an active metabolite
13
Q
What are the three hormone secretion patterns?
A
continuous release e.g. prolactin
pulsatile release e.g. insulin
circadian release e.g. cortisol
14
Q
How does hormone metabolism affect hormone action?
A
when metabolism increases, hormone function reduces
15
Q
How is hormone action increased?
A
hormone receptor induction (increasing number/concentration of hormone receptors)
Synergism (combined effects of two hormones amplified) e.g. glucagon and adrenaline
16
Q
How is hormone action decreased?
A
Hormone metabolism
Hormone receptor downregulation (large quantities of hormones secreted causes down regulation of target receptors)
Antagonism (one hormone opposes another) e.g. glucagon an insulin
17
Q
Which hormones does the hypothalamus release to the anterior pituitary?
A
Thyrotropin releasing hormone / TRH
Corticotropin Releasing Hormone / CRH
Growth Hormone Releasing Hormone / GHRH
Prolactin Releasing Hormone
Gonadotropin Releasing Hormone / GnRH
18
Q
Which hormones does the anterior pituitary release?
A
Thyroid Stimulating Hormone / TSH
Adrenocorticotropic Hormone / ACTH
Growth Hormone / GH
Prolactin
Gonadotropins -> LH and FSH
19
Q
Which hormones does the hypothalamus produce for storage in the posterior pituitary?
A
Anti-diuretic hormone (ADH) / Vasopressin
Oxytocin
20
Q
How is the hypothalamus connected to the anterior and posterior pituitary?
A
Linked to the anterior pituitary via blood vessels
Linked to the posterior pituitary via nerves
21
Q
What are the two main functions of oxytocin?
A
- ejection of milk during breastfeeding
- contraction of smooth muscle in uterus -> labour
22
Q
What are the functions of ADH?
A
- decreases water secretion in the urine by inserting aquaporins in the collecting duct for H2O reabsorption
- Acts on smooth muscles in the blood vessels causing vasoconstriction and increasing blood pressure
- Stimulates ACTH release to increase aldosterone release which increases fluid retention
23
Q
What are the functions of growth hormone?
A
Stimulates growth
1. acts on liver to increase protein synthesis and stimulates IGF1 (Insulin-like Growth Factor 1)
- IGF1 acts on the skeleton to increase cartilage proliferation and skeletal growth
2. stimulates gluconeogenesis and inhibits insulin - increasing glucose levels
3. increases breakdown of fat in adipose tissue
24
Q
Describe the hypothalamo-pituitary-thyroid axis
A
Hypothalamus releases thyrotropin releasing hormone to anterior pituitary
Anterior pituitary then releases thyroid stimulating hormone to the thyroid
thyroid then releases T3 and T4
25
Describe thyroid hormones
T3 (triiodothyronine) - more active, about 20% of secretions
T4 (thyroxine) - less active, about 80% of secretions
T4 is converted to T3 in periphery
26
What are the functions of T3?
Increases food (carbohydrate and fat) metabolism
Increases protein synthesis
Increases ventilation rate
Increases heart rate and cardiac output
Increases growth rate
Important for foetal and postnatal brain development
27
Describe the hypothalamo-pituitary-adrenal axis
Hypothalamus releases corticotropin releasing hormone to AP
Anterior pituitary releases adrenocorticotropic hormone to adrenal glands
Adrenal cortex releases cortisol, androgens, adrenaline
28
Which hormones are released from which layers in the adrenal glands?
Zona glomerulosa - mineralocorticoids (aldosterone -> stimulated by angiotensin II)
Zona fasciculata - glucocorticoids (cortisol)
Zona reticularis - gonadotropins/androgens (testosterone) -> sex hormones
Adrenal medulla - adrenaline
29
What are the actions of cortisol?
1. Helps overcome stress
2. regulation and breakdown of proteins, fats and carbohydrates, increasing blood glucose
3. Anti-inflammatory effect
4. Keeps us awake
30
Describe the hypothalamo-pituitary-gonadal axis
hypothalamus releases gonadotropin releasing hormone to the AP
Anterior Pituitary releases FSH and LH to the gonads
31
Describe the action of FSH and LH in females and the negative feedback loop
FSH and LH travel to the ovaries and stimulate oestrogen production
Oestrogen helps regulate menstrual cycle
FSH stimulates he development of ova
LH stimulates ovulation
Inhibin is produced by granulosa cells which inhibits GnRH secretion (with oestrogen)
Oestrogen inhibits GnRH
32
Describe the action of FSH and LH in males and the negative feedback loop
FSH acts on sertoli cells to initiate spermatogenesis
LH acts on Leydig cells to stimulate testosterone secretion
Testosterone travels to sertoli cells to facilitate spermatogenesis
Testosterone inhibits GnRH secretion and LH secretion
Sertoli cells release inhibin to inhibit FSH release
33
Describe the release of prolactin
Hypothalamus releases prolactin releasing hormone to AP
Anterior pituitary releases prolactin to the mammary glands
34
What is the function of prolactin?
Stimulates mammary glands to produce milk
Helps with breast development
35
What is prolactin inhibited by?
Dopamine
36
What is the function of RAAS?
To increase/maintain blood volume and blood pressure
37
Where is renin secreted from?
Juxtaglomerular cells of kidneys
38
What stimulates the release of renin?
A drop in blood pressure
Drop in sodium concentration of distal convoluted tubule
Sympathetic stimulation
39
Describe RAAS
Liver secretes angiotensinogen
Kidney secretes renin which converts angiotensinogen to angiotensin I
Lungs secrete angiotensin converting enzyme (ACE) which converts angiotensin I to angiotensin II
Angiotensin II acts on the adrenal gland to stimulate the release of aldosterone
40
What is angiotensinogen?
A protein produced and stored in the liver
Converted to angiotensin I by renin
41
What is angiotensin I?
Not much function
Converted from angiotensinogen by renin
Converted to angiotensin II by ACE
42
What is ACE?
Angiotensin Converting Enzyme
Converts angiotensin I to angiotensin II
A common drug target for lowering blood pressure
43
What is angiotensin II?
Converted from angiotensin I by ACE
Acts directly on smooth muscle in vessels, causing vasoconstriction and increasing BP
Stimulates aldosterone secretion from the adrenal cortex
Stimulates the thirst response from the hypothalamus
44
Why does the thirst response increase blood pressure?
Anti-diuretic hormone is released from the posterior pituitary gland causing H2O reabsorption in the kidneys.
Blood volume and blood pressure then increases
45
What is aldosterone?
A hormone secreted from the zone glomerulosa of the adrenal glands
It acts on the kidneys to increase Na (and therefore H2O) reabsorption in the tubules, increasing blood volume and BP
46
Define appetite
the desire to eat food
47
Define hunger
the need to eat food
48
Define anorexia
a lack of appetite
49
Define satiety
The feeling of fullness
The disappearance of appetite after a meal
50
Describe the satiety cascade
An internal psychological drive to eat -> prompts thought of food and motivates food consumption
An external physiological drive to eat (sometimes in the absence of hunger)
51
What is the hunger centre?
the lateral hypothalamus (the eating accelerator)
52
What is the satiety centre?
The ventromedial hypothalamus (the eating brake)
53
What is the calculation for body mass index?
BMI = weight (kg) / height^2 (m^2)
54
Which central controllers of appetite in the hypothalamus increase appetite?
Neuro Peptide Y (NPY)
Agouti-related peptide (AgRP)
Ghrelin
55
Which central controllers of appetite in the hypothalamus decrease appetite?
POMC
CART
Glucagon like peptide 1 (GLP-1)
Leptin
Insulin
Peptide YY
Cholecystokinin
56
What does Ghrelin do?
Stimulates growth hormone release
Increases appetite
57
What does Agouti Related Peptide do?
Stimulates appetite and feeding
58
What does leptin do?
Binds to a receptor in hypothalamus and 'switches off' appetite and increases satiety
A deficiency of leptin leads to obesity
59
What does cholecystokinin do?
Binds to receptors in the pyloric sphincter -> delays gastric emptying, stimulates gallbladder contraction (releasing bile) and stimulates insulin release
Stimulates the vagus nerve
Decreases appetite
60
What does peptide YY do?
Secreted in ileum, pancreas and colon in response to food and binds to NPY receptors -> inhibits gastric motility and decreases appetite
61
What does GLP-1 do?
Released in response to feeding
Decreases gut motility, increases satiety, decreases appetite, increases insulin release and decreases glucagon release from pancreas
62
What is Diabetes mellitus type 1?
a chronic metabolic disease which destroys pancreatic beta cells causing insulin deficiency
63
What is the epidemiology of DM T1?
Generally affects younger people and Northern European people
64
What is the aetiology of DM T1?
Usually autoimmune (Type IV hypersensitivity)
Can also be caused by viruses or unknown cause
65
What are the risk factors of DM T1?
Genetic predisposition
66
What is the pathophysiology of DM T1?
Beta cells of the pancreas are destroyed
Insulin is not produced
Glucose can't be taken up by cells, leading to hyperglycaemia
67
What are the clinical manifestations of DM T1?
Polyuria
Polydipsia
Weight loss
Fatigue and lethargy
Recurrent vaginal candida
Moderate/large urinary ketones
Blurred vision
Diabetic ketoacidosis
68
What investigations would you do for someone with suspected DM T1?
Fasting glucose (>7mmol/L)
Non-fasting/random glucose (>11mmol/L)
HbA1c >6.5%
Urinalysis showing high albumin
Autoantibodies present
C Peptide low
69
How would you distinguish Type 1 DM from T2?
Autoantibodies will be present in Type 1 but not Type 2
C peptide (measure of insulin production) is low in Type 1 but normal or elevated in Type 2
70
What is the management of Type 1 DM?
1. Basal bolus of insulin, can be short or long acting. Long acting insulin given 1-2 times a day and short acting supplement before each meal
Regular monitoring of blood glucose
Life style advice - carb-counting
2. Mixed insulin (short and long acting)
3. continuous insulin infusion if severe hypoglycaemia or permanently hyperglycaemic on multiple injections a day
71
What is the differential diagnosis of DM T1?
Type 2 DM
Other types of diabetes mellitus
Other causes of hyperglycaemia
72
What are the complications of DM T2 divided into?
Diabetic ketoacidosis (if it is poorly managed or ill)
Macrovascular complications and microvascular complications
Hypoglycaemia from medication
73
What is the prognosis of DM T1?
Fairly normal life expectancy if well managed
Normally have at least 1 serious complication
74
What are the macrovascular complications of Diabetes Mellitus?
Macrovascular: Coronary artery disease, peripheral artery disease, diabetic foot ulcers
Microvascular: retinopathy, nephropathy, neuropathy
75
How does DM cause Coronary Artery Disease and peripheral vascular disease?
High glucose levels in the blood cause endothelial damage in blood vessels over time
This leads to atherosclerosis
76
How does DM cause retinopathy?
Glucose blocks the vessels to the retina causing them to leak fluid or blood. New vessels grow to replace them but aren't effective in blood delivery so the retina gets damaged
77
How does DM cause nephropathy?
Hyperglycaemia causes vessel damage
Increased glucose concentration in the urine causes glomerulosclerosis (scarring of the glomerulus), decreasing renal function
78
How does DM cause neuropathy?
Hyperglycaemia causes damage to the vessels supplying the nerves, causing damage
79
What is diabetic ketoacidosis?
A metabolic state which is a potentially fatal complication of Type 1 Diabetes Mellitus
It may be the first presentation of T1 DM
80
What is the pathophysiology of diabetic ketoacidosis?
The liver produces ketones as a fuel despite hyperglycaemia (less glucose being driven into cells so lipid metabolism to produce ketones) -> uncontrolled lipolysis
Ketones are acidic and the overproduction uses all the bicarbonate (buffer) in the blood so the blood becomes acidic
81
What are the key features of Diabetic Ketoacidosis?
Hyperglycaemia
Acidosis
Ketonaemia
Dehydration
Potassium imbalance
82
What is the treatment for Diabetic Ketoacidosis?
IV Saline (0.9% NaCl). Different length of infusion time depending on blood pressure (longer for higher BP)
Potassium may need to be replaced so may have NaCl with KCl
83
What is Diabetes Mellitus Type 2?
An increased resistance to insulin
There may also be decreased insulin production
84
What is the epidemiology of DM T2?
Increasing prevalence
Approximately 90% of diabetes in high income countries
Generally later onset but doesn't have to be
85
What is the aetiology of DM T2?
Acquired or inherited insulin resistance
86
What are the risk factors for DM T2?
Family history
Physical inactivity
Having excess weight/obesity
Being over 45 years old
High carbohydrate/sugar diet
History of: gestational diabetes, pre diabetes, polycystic ovary syndrome
87
What is the pathophysiology of DM T2?
Repeated (over) exposure to glucose and insulin increases insulin resistance
Insulin production increases to stimulate cells to take up glucose and compensate for the resistance
The pancreas fatigues and gets damaged over time from the over production of insulin
Insulin output decreases
Resulting in hyperglycaemia
88
What are the clinical manifestations of DM T2?
Polyuria
Polydipsia
Weight loss due to dehydration
Fatigue and lethargy
Recurrent vaginal candida
Moderate to large urinary ketones
Blurred vision
Usually gradual onset
89
What investigations would you do for someone with suspected DM T2?
HbA1c >6.5%
Fasting glucose (>7mmol/L)
Random/non-fasting glucose (>11mmol/L)
Autoantibodies absent
C peptide normal or elevated
90
What is the management of Type 2 DM?
1st line: metformin
Diet and exercise changes to control weight
May also have SGLT-2 inhibitors (increase glucose excretion in kidneys) and sulphonylureas (increase insulin production and sensitivity)
Eventually may use insulin - avoid for as long as possible to preserve insulin sensitivity
91
What are the complications of DM T2?
Hyperosmolar Hyperglycaemic State (HHS)
Macrovascular complications: coronary artery disease, peripheral vascular disease, diabetic foot ulcers
Microvascular complications: retinopathy, nephropathy, neuropathy
Hypoglycaemia from medication
92
What is the differential diagnosis for DM T2?
Type 1 DM
Other types of DM
Other causes of hyperglycaemia
93
What is the prognosis of DM T2?
Fairly normal life expectancy if well managed
Most people will get at least one serious complication
94
What is Hyperosmolar Hyperglycaemic State?
A potentially fatal complication of Type 2 DM
It may be the fist presentation of T2 DM
95
What is the pathophysiology of HHS?
Hyperglycaemia drives an osmotic diuresis with subsequent fluid and electrolyte loss → hyperosmolality and hypovolaemia
Due to the presence of small amounts of circulating insulin in T2DM , lipolysis does not occur and hence ketoacidosis is not seen , unlike in diabetic ketoacidosis (DKA)
96
What are the key features of HHS?
Hyperosmolality (concentrated blood due to water loss)
Hyperglycaemia
Absence of ketones
Dehydration
Weight loss (from dehydration)
Polyuria
Polydipsia
Tachycardia
Hypotension
Confusion
97
What is the treatment of HHS?
Fluid replacement, normalise blood glucose, normalise osmolality
Fluid resuscitation first
If needed, then insulin infusion after
Replace potassium
Should be done gradually (over 72 hours) to avoid complications
98
Define overweight/obesity
Abnormal or excessive accumulation of fat that presents a risk to health
99
What BMI is a normal?
18.5-24.9
100
What BMI is underweight?
<18.5
101
What BMI is overweight?
25-29.9
102
What BMI is obese?
30-39.9
103
What BMI is morbidly obese?
>40
104
What are the main causes and risk factors of overweight/obesity?
1. Genetic factors (accounts for 40-50% of bodyweight variability)
2. Co-morbidities and health connections e.g. endocrine dysfunction, depression etc
3. Environmental factors e.g. food deserts, ultra processed food, low activity environment, advertising and marketing
4. Behavioural factors e.g. food choices, societal and cultural norms
105
What is the management of obesity?
1. Diet - healthy, balanced diet; plenty of fruit and veg; low salt, sugar and fat
2. Exercise - 150 mins of moderate to high intensity
3. Weight loss drugs (e.g. semaglutide) or surgery
106
What is the primary prevention of obesity?
Keeping healthy from an early age e.g. breastfeeding, food environment, physical activity, health education, advertising control
107
What is the secondary prevention of obesity?
Healthy diet intervention
Physical activity
Weight loss support programmes
Education
108
What is the tertiary prevention of obesity?
Physical activity
Healthy diet
Compassionate approach and stigma reduction
Mental health approach
Pharmaceuticals
Bariatric surgery
109
What does Diabetes Mellitus screening look for?
Impaired glucose tolerance
Impaired fasting glucose
110
What are the current screening tests available for diabetes mellitus?
HbA1c
Random capillary blood glucose
Random venous blood glucose
Fasting venous blood glucose
Oral glucose tolerance test
111
What does HbA1c tell us?
An average blood glucose level over the past 3 months
112
What is Maturity Onset Diabetes of the Young (MODY)?
Single gene mutation
Beta cell function is impaired leading to impaired glucose sensing and insulin secretion
113
How is MODY different from other types of diabetes?
MODY is a single gene mutation whereas Type 1 and 2 are polygenetic
MODY isn't autoimmune and doesn't involve insulin resistance
114
What are the typical features of MODY?
Presentation < 25 years of age
Strong family history
Normal BMI
Lack autoantibodies
No ketosis
Insulin not usually required
115
What is the main treatment of MODY?
Sulphonylureas
116
What is Permanent Neonatal Diabetes?
Beta cells are unable to secrete insulin due to a genetic mutation
Rare
117
What is Drug-Induced Diabetes?
When glucocorticoids (or other drugs) cause insulin resistance
Other drugs could be: thiazide diuretics, protease inhibitors, antipsychotics
118
What is the function of calcium?
Increases contractile ability of excitable tissues
Therefore involved in regulation of cardiac rhythm, skeletal muscle function, nerve function, kidney function
119
What substances are involved in the calcium homeostasis?
Parathyroid hormone
Vitamin D
Calcitonin
120
What is the function of the parathyroid gland?
To release parathyroid hormone if serum calcium is too low
121
What are the actions of parathyroid hormone?
1. increases calcium reabsorption in the kidneys
2. decreases phosphate reabsorption in the kidneys
3. increases 1 alpha hydroxylation of 25 hydroxy vitamin D in the kidneys
4. Increases osteoclast activity to increase bone resorption
5. increases calcium absorption in the intestines (due to increased 1,25-dihydroxyvitamin D
122
Describe the synthesis of Vitamin D
1. UV light from the sun interacts with 7-dehydrocholesterol in the skin to produce cholecalciferol (vitamin D3)
2. Cholecalciferol is also consumed in food
3. Ergocalciferol (vitamin D2) is also consumed in food
4. Cholecalciferol and Ergocalciferol travel in the blood to the liver
5. The liver converts both to calcidiol (25hyroxyvitamin D)
6. Calcidiol travels in the blood to the kidneys where it is converted to Calcitriol
Calcitriol is 1,25-dihydroxyvitamin D -> the functional form of vitamin D
123
What is calcitonin?
Produced in the thyroid
Directly inhibits osteoclast activity (inhibits bone resorption)
Released in hypercalcaemia
Not essential to life
124
What are the causes of hypercalcaemia?
Malignancy
Hyperparathyroidism
125
What is hypercalcaemia of malignancy?
Malignant tumours secrete parathyroid-like protein
This causes hypercalcaemia
There is low/undetectable parathyroid hormone
126
What are the types of hyperparathyroidism?
Primary
Secondary
Tertiary
127
What is primary hyperparathyroidism?
A tumour of the parathyroid glands (generally an adenoma of one gland)
Causes excess PTH secretion
Leading to hypercalcaemia
The most common cause of hyperparathyroidism
128
What are the symptoms of primary hyperparathyroidism?
Generally asymptomatic but could have:
Stone - renal
Bones - osteoporosis etc
Moans - abdominal -> constipation, acute pancreatitis
Groans (psychic) - confusion
129
What is the treatment of primary hyperparathyroidism?
Treat the underlying cause, usually with surgery
130
What is secondary hyperparathyroidism?
Calcium absorption is reduced, usually due to Vitamin D deficiency or Chronic Kidney Disease
Hypocalcaemia so high PTH to compensate
131
What is the treatment for secondary hyperparathyroidism?
Treat the underlying cause e.g. kidney transplant, vitamin D supplements
132
What is tertiary hyperparathyroidism?
When secondary hyperparathyroidism has continued for an extended period of time but is then treated
There has been hyperplasia of the parathyroid glands to compensate so PTH production remains high, resulting in hypercalcaemia
133
What is the treatment of tertiary hyperparathyroidism?
Surgery to remove of the the parathyroid tissue
134
What are the presentations of hypocalcaemia?
SPASMODIC
Spasms - Trousseau's sign
Parasthesiae (around mouth and extremities)
Anxious, irritable, irrational
Seizures
Muscle tone increases in smooth muscle -> wheeze
Orientation impaired and confusion
Dermatitis, Diarrhoea
Impetigo herpetiformis (in pregnancy)
Chvostek's sign, Cardiomyopathy, Cataract
135
What is Troussaeu's sign?
Carpopedal spasm induced by BP cuff inflation
Positive (spasm) indicated hypocalcaemia
136
What is Chvostek's sign?
Tapping over the facial nerve in the region of th parotid glands causes facial muscle twitches ipsilaterally
137
What are the causes of hypocalcaemia?
