Endocrine Flashcards
(377 cards)
1
Q
Define diabetes
A
A disorder of carbohydrate metabolism characterised by chronic hyperglycemia due to relative insulin deficiency (type 1) or insulin resistance (type 2)
2
Q
What is the principal organ of glucose homeostasis
A
Liver
3
Q
Normal physiological response when need to increase blood glucose (2 processes)
A
Glycogenolysis
Gluconeogenesis
Controlled by glucagon
4
Q
Main insulin independent tissue
A
Brain
5
Q
Why is brain the major consumer of glucose
A
Brain function is dependent on a continuous supply as it cannot use free fatty acids for energy as they cannot cross the blood brain barrier
6
Q
Normal physiological process after feeding
A
Increase in blood glucose 5-10 mins after feeding stimulates insulin secretion and suppresses glucagon
60% of ingested glucose goes to the periphery (muscle) to replenish the glucose store
40% of ingested glucose goes to the liver - glycogenesis
7
Q
Roles of insulin
A
Decrease hepatic glucose output
Increase glucose uptake into insulin sensitive tissues
Suppresses lipolysis and decreases ketogenesis
8
Q
Physiology of insulin secretion by the beta cell
A
- GLUT-2 glucose transporter has a low affinity for glucose. Glucose flows freely into the beta cell
- Glucose is phosphorylated by glucokinase
- Increase rate of ATP formation from ADP
- Increased ATP concentration closes the K+ channels
- Change in membrane polarity
- Voltage gated Ca2+ channels open and Ca2+ ions enter the cell
- Increased concentration of Ca2+ causes insulin vesicles to move to the outer cell membrane
- Insulin is secreted
9
Q
What form is insulin secreted in
A
Insulin is secreted as proinsulin. Alpha and beta chains are joined together by C peptide. Once proinsulin is secreted C peptide is cleaved off
10
Q
What is biphasic insulin release
A
First rate response = rapid as it is the release of stored insulin
Second rate response = slower release of newly synthesised insulin
11
Q
What is the action of insulin in muscle and fat cells
A
- Insulin binds to insulin receptor on the muscle/fat cell
- The binding activates tyrosine kinase which triggers an intracellular signalling cascade
- Insulin mobilises GLUT-4 vesicles in the cell which migrate to the plasma membrane
- GLUT-4 vesicles are integrated into the plasma membrane
- GLUT-4 vesicles allow glucose to enter the cell
12
Q
How can you increase GLUT-4 receptors
A
The more glucose there is the more GLUT-4 receptors there are
13
Q
How can you increase insulin sensitivity
A
Exercise can increase insulin sensitivity
14
Q
What is type 1 diabetes
A
Inadequate insulin production and secretion by the beta cells of the pancreas caused by autoimmune destruction
15
Q
Epidemiology of type 1 diabetes
A
Typically is adolescent presentation
Lean patient
Increase prevalence in those of N.European ancestry
16
Q
Risk factors for type 1 diabetes
A
Northern European (esp Finnish)
Family history
Genes : HLA-DR3 and HLA-D4
Other autoimmune diseases (i.e Grave’s, coeliac)
17
Q
Pathogenesis of type 1 diabetes
A
Type IV hypersensitivity reaction as T cells attack the pancreatic beta cells due to their loss of self tolerance
Destruction of the beta cells causes insulin deficiency as it is not secreted by the cells.
Autoantibody formation against islet beta cells
18
Q
Consequences of the failure of insulin secretion
A
No insulin leads to…
1. No insulin effect on muscle / fat –> impaired glucose clearance and muscle increased muscle/fat breakdown –> less glucose enters the peripheral tissue
2. No hepatic insulin effect –> unrestricted production of glucose and ketones –> more glucose enters the blood
Leads to hyperglycaemia and increase in plasma ketones
Glycosuria and ketonuria
19
Q
How many beta cells are typically destroyed at the time symptoms develop in type 1 diabetes
A
90%
20
Q
What would happen if you didn’t treat type 1 diabetes with insulin
A
Increased concentration of glucagon in the circulation (due to the loss of local insulin within the islets there is no negative feedback and inhibition of glucagon release)
State of perceived stress leads to increased cortisol and adrenaline
Progressive catabolic state leads to increased ketones
21
Q
Clinical presentation of type 1 diabetes (symptoms)
A
Polyuria and nocturia Polydipsia Unexplained weight loss Usually an acute presentation of a young person 2-6 week history
22
Q
Why polyuria and nocturia in presentation?
A
Not enough glucose can be reabsorbed by the kidneys as they have reached the renal threshold for maximum resorptive capacity
Increased glucose in the tubule so less water being reabsorbed by osmosis
Increased urine output
23
Q
Why polydipsia in presentation?
A
Due to loss of electrolytes and fluid in urine
24
Q
Why is there weight loss in type 1 diabetes presentation
A
Due to fluid depletion and accelerated breakdown of fat and muscle secondary to insulin deficiency
Catabolic state - loss of muscle
Hunger
25
Signs of type 1 diabetes
Glycosuria
Ketonuria
Patient's breath may smell like pears (ketones)
26
Complications as the presenting complaint (type 2)
Staphylococcal skin infection
Retinopathy
Neuropathy
Erectile dysfunction
27
What investigations would you do in someone with suspected diabetes
Random plasma glucose
Fasting plasma glucose
Oral glucose tolerance test
HbA1c
28
What is the oral glucose tolerance test
Patient fasts for 8-12 hours before you take their blood
| Give 75mg of glucose and test blood two hours later
29
What is HbA1c
Measures of the amount of glycerated haemoglobin
| It assess the blood glucose level over the past few months (120 days ~ RBC lifespan)
30
Other tests in your investigation for patients with diabetes that does not include looking at blood glucose levels ?
FBC
U&Es
Screen urine for microalbuminuria to assess for kidney disease
blood pH to look for ketoacidosis
31
What is diagnostic for random plasma glucose
11.1mmol/L or more
32
What is diagnostic for fasting plasma glucose
7.0 mmol/L or more
33
What is diagnostic for HbA1c
48 or more
| 6.5% or more
34
What do you need to diagnose diabetes
Abnormal HbA1c
One abnormal random or fasting plasma glucose + symptoms
Two abnormal results for random and fasting plasma glucose if asymptomatic
35
Principles of treatment of diabetes (type 1 and 2)
1. control of symptoms
2. prevention of acute emergencies
3. identification and prevention of long-term microvascular complications
4. Patient education on their disease and risks
5. Maintain a lean weight, don't smoke and take care of feet
36
What is the treatment for type 1 diabetes
insulin
37
How is insulin administered
subcutaneous injection into the abdomen (fastest absorption rate)
38
How is insulin activated
GI enzymes
39
What factors can change insulin absorption
local tissue reactions
changes in insulin sensitivity
injection site
blood flow
40
why is it important to change up the injection site for insulin
to prevent lipohypertrophy (fatty lumps)
41
what are the three groups of insulins
short-acting insulin
intermediate acting insulin
long acting insulin
42
What is the first line choice treatment for an insulin regime
multiple daily injection basal-bolus insulin
one or more separate daily injections of intermediate acting insulin or long-acting insulin analogue as the basal insulin
alongside multiple bolus injections of short acting insulin before meals
43
what is the biphasic regime
1,2 or 3 insulin injections per day of short acting insulin mixed with intermediate-acting insulin
44
what is continuous insulin infusion
insulin pump
regular or continuous amount of insulin (usually rapid-acting insulin analogue or soluble insulin) delivered by a programmable pump and insulin storage reservoir via a subcutaneous needle
45
symptoms of hypoglycaemia
```
hungry
sweating
tingling lips
tremor
weakness
blurred vision
easily irritable
```
46
complications of insulin therapy
hypoglycaemia
insulin resistance - mild
lipohypertrophy
weight gain
47
define type 2 diabetes
caused by decreased insulin resistance with or without decreased insulin secretion
48
Epidemiology of type 2 diabetes
common in all populations enjoying an affluent lifestyle
Increasing incidence due to ageing population and increasing obesity in the west
older patients over 40 yrs old
Increased prevalence in men
More prevalent in south asian, african and caribbean ancestry
49
Risk factors for type 2 diabetes
```
family history - first degree relatives. There is a stronger genetic link in type 2 diabetes than type 1
Increasing age
obesity
sedentary lifestyle
ethnicity
pmh gestational diabetes
pmh of heart disease or stroke
high waist circumference
hypertension
low level of HDL cholesterol
smoking
excessive alcohol consumption
```
50
pathogenesis of type 2 diabetes
1. insulin dependent cells do not respond to insulin (resistance - post receptor)
2. excess adipose tissue releases FFA that can cause inflammation and influence cell resistance
3. beta cells undergo hyperplasia and hypertrophy to increase insulin secretion
4. beta cells secrete amyloid polypeptide and amylin
5. amylin builds up and aggregates in the islets leading to amyloid deposits in the beta cells
6. beta cells become dysfunctional and undergo hypoplasia and hypotrophy
7. impaired insulin secretion
8. hepatic insulin resistance --> excessive glucose production --> more glucose enters bloodstream
9. muscle / fat insulin resistance --> decreased glucose uptake after a meal --> impaired glucose clearance and less glucose enters peripheral tissues
10. hyperglycaemia
11. glycosuria
51
what is impaired glucose tolerance
HbA1c of 42-47 mmol/L
| A unique window for lifestyle intervention
52
clinical presentation of type 2 diabetes
```
overweight
increased visceral fat
polydipsia
polyuria
weight loss
usually a subacute presentation and onset is over several months or years
```
53
why is ketoacidosis rare in type 2
low insulin levels are sufficient to suppress catabolism and prevent ketogenesis
54
investigations of type 2 diabetes
same tests as type 1
older patients may present with established complications - retinopathy
patients with severe insulin resistance may have acanthosis nigricans (blackish pigmentation at the nape of the neck and axillae)
55
Objectives of treatment of type 2
manage blood glucose
reduce risk of: CVD mortality and morbidity, CKD, microvascular complications
Weight reduction : increase physical activity and decrease dietary fats
56
progression of treatment in type 2 diabetes
```
Lifestyle
metformin
dual therapy
triple therapy
insulin
```
57
lifestyle interventions and advice for type 2 diabetes patients
community run lifestyle education programmes e.g DESMOND
Moderately rigorous activity for up to 30 minutes a day
Reduce portion sizes
Diet : low carbohydrate diets, low sugar with high in starch carbohydrates with a low glycaemic index
Stop smoking
Control of blood pressure e.g with ramipril
Hyperlipidaemia control e.g statins
Can give orlistat in obesity (intestinal lipase inhibitor) that reduces absorption of fat from the diet
58
What is second line therapy for type 2 diabetes
metformin
59
what type of drug is metformin
biguanide drug
60
mechanism of metformin
oral drug that works by preventing the production of glucose in the liver, improving the body's sensitivity towards insulin and reducing the amount of sugar absorbed by the intestines
61
what does metformin do
reduces the rate of gluconeogenesis in the liver
increases cells sensitivity to insulin
weight loss promotion
reduces CVD risk in diabetes
62
Side effects of metformin
anorexia
diarrhoea
nausea
abdominal pain
63
What drugs can we use as second line dual therapy?
sulfonylurea
pioglitazone
incretin based agents (GLP-1 receptor agonist, DPP-4 inhibitors)
SGLT-2 inhibitor
64
what is the mechanism of sulfonylurea
pushes the beta cells in the pancreas to produce more insulin
rapid improvement in glycaemic control
65
cons to using sulfonylurea
overtime it loses its effectiveness (6-8 years)
| causes weight gain initially
66
example of a sulfonylurea
gliclazide
67
what are incretins
hormones secreted by intestinal endocrine cells in response to nutrient intake
they influence glucose homeostasis by: glucose-dependent insulin secretion, postprandial glucagon suppression and slowing of gastric emptying
68
What is the effect of GLP-1 in humans
glucose enters gut
GLP-1 hormone is released which increases insulin production and promotes satiety, decreasing appetite
Lowers blood sugars
Broken down by DPP-4
69
example of a GLP-1 receptor agonist
exenatide
70
mechanism of a GLP-1 receptor agonist
increases GLP-1 levels
| induces a delay in gastric emptying
71
benefit of a GLP-1 receptor agonist
induces weight loss by 3-4 kg
72
who can start on GLP-1 receptor agnoists
patient has to have a BMI greater than 35
73
example of a DPP-4 inhibitor
sitagliptin
74
what do DPP-4 inhibitors do
small increase in endogenous GLP-1
75
example of an SGLT-2 inhibitor
empagliflozin
76
mechanism of SGLT-2 inhibitors
works on the kidneys by reducing the resorption of glucose in the kidneys at the PCT
increases renal excretion of glucose and decreases blood glucose
77
when do we use SGLT-2 inhibitors
these are increasingly being used as second line treatment for dual therapy after metformin
78
complications of SGLT-2 inhibitors
GU infections due to increased glycosuria
affect women more than men
easily managed and patients need to be reassured about continuing the treatment
79
side effect of SGLT-2 inhibitors
may cause intravascular volume depletion
| need to monitor patients for symptoms of hypotension
80
mechanism of action of pioglitazone
increases insulin sensitivity
81
side effects of pioglitazone
hypoglycaemia
fractures
fluid retention
can increase weight
82
contraindications of using pioglitazone
congestive heart failure
osteoporosis
macula oedema
83
risks of developing diabetic retinopathy
```
long duration of diabetes
poor glycaemic control
hypertensive
on insulin
pregnant
```
84
what is an effective way of preventing patients developing early diabetic retinopathy
eye screening
anyone over the age of 11 with diabetes
photographs are taken and graded
85
pathogenesis of diabetic retinopathy
1. hyperglycaemia triggers apoptosis of pericytes
2. causes localised outpouching of capillary walls
3. microaneurysms form
4. microaneurysm formation + smooth muscle cell loss can lead to leakages
5. breach of microaneurysm causes fluid to leak into the retina
6. fluid is cleared by the retinal veins and leaves behind protein and lipid deposits
7. retina compensates for loss of cells by growing new glial cells in capillaries
8. leads to occlusion
9. pericyte loss causes endothelial cells to increase turnover which can cause thickening (ischaemia)
10. ischaemia leads to release of vascular growth factors that cause new blood vessels to grow which are prone to haemorrhaging
86
how can you see evidence of diabetic retinopathy on a photograph
red dots = microaneurysms
| yellow-white hard exudates blots = protein and lipid deposition in renal veins
87
treatment for diabetic retinopathy
laser treatment aims at stabilising changes
does not improve sight
if given at the correct stage it is very effective
88
what feature can you see in advanced diabetic retinopathy
cotton wool spots are seen in maculopathy
| caused by the fibrosis
89
what are the microvascular complications of diabetes
retinopathy
neuropathy
nephropathy
90
what are the macrovascular complications of diabetes
stroke
cardiovascular disease (leading cause of mortality)
peripheral vascular disease
91
pathogenesis of diabetic nephropathy
1. hyperglycaemia leads to formation of advanced glycosylation endproducts
2. these accumulate in the basement membrane and cross link with collagen
3. thickening of basement membrane
4. membrane becomes more permeable
5. glomerular hyperperfusion and hyperfiltration occurs
6. increases likelihood that proteins will pass through
92
what is the hallmark of the clinical presentation of diabetic nephropathy
proteinuria - urine dipstick test
93
difference between when clinical presentation of diabetic nephropathy in type 1 and type 2 patients
type 1 : develops 5-10 years after diagnosis
| type 2 : may already be present at the time of diagnosis
94
ways to slow progression of diabetic nephropathy
```
about controlling proteinuria by:
good glycaemic control
blood pressure control
blockage of RAAS with ACE-inhibitors
cholesterol control
```
need to intervene and treat aggressively to stop declining renal function
95
example of an ACE-inhibitor
Ramipril
96
Example of a statin
simvastatin
97
why is diabetes a huge risk factor for cardiovascular disease
most diabetic patients are dyslipidemic
dyslipidemia is highly correlated with atherosclerosis
atherosclerosis is associated with nearly all CVD
98
what is peripheral vascular disease
decreased perfusion due to macrovascular disease at more distal sites
99
symptoms of peripheral vascular disease
intermittent claudication
| rest pain
100
signs of peripheral vascular disease
pulselessness, pain, pallor, paresthesia and paralysis
| 5 Ps
101
how to evaluate peripheral vascular disease
Doppler pressure studies measures the amount of blood flow through arteries and veins
102
treatment of PVD
stop smoking
walk through the pain
surgical intervention may be needed
103
what is diabetic neuropathy
a decrease in sensation in the glove and stocking distribution
pathogenesis of the pain is unknown
104
treatment for DN
no cure, so most treatment is symptomatic to reduce their pain
- good glycaemic control
- paracetamol
- anticonvulsants e.g gabapentin
- opioids e.g tramadol
- IV lignocaine
- amitriptyline
105
what is the progression of treatment for diabetic neuropathy
work up the analgesics ladder
| paracetamol --> gabapentin --> tramadol
106
Risk factors for developing diabetic neuropathy
```
hypertension
smoking
high HbA1c
duration of diabetes
high BMI
increase in triglycerides
```
107
consequences of diabetic neuropathy
diabetic foot ulceration which can lead to amputation
108
what is the progression from diabetic neuropathy to amputation
1. neuropathy
2. trauma
3. ulcer
4. failure to heal
5. infection
6. amputation
109
symptoms of diabetic neuropathy
pain (burning, paraesthesia, allodynia, worse at night)
autonomic (orthostatic hypotension, constipation, ED)
insensitivity (foot ulceration, infection)
110
pathophysiology of diabetic foot
1. trauma happens to the foot (patient cannot feel this as have lost sensitivity so have no feeling of pain)
2. this can lead to ulcer formation
additionally :
- because of deformities in the foot there is more pressure on metatarsal heads so calluses build up which can push against healthy skin underneath and damage it
- can get autonomic nerve damage i.e no sweating so get cracks and fissures and allow infection to sit it
111
investigation of diabetic foot
early recognition is vital!!!!
1. test sensation
- 10mg monofilament
- neurotips
2. vibration perception
- tuning fork
3. ankle reflexes (may be absent)
4. look at shoes for any foreign bodies
5. look at the feet - any skin changes e.g pallor, decreased temp
6. look for the presence of any ulcers
7. pulses - doralis pedis, posterior tibial
112
management of diabetic foot
educate patient
daily foot inspection
comfortable and therapeutic shoes
regular chiropody to remove callus as haemorrhage and tissue necrosis may occur leading to ulceration
113
what is the management if the patient has a foot ulcer
```
MDT clinic every 2 weeks until the ulcer has healed
pressure relieving footwear
podiatry
revascularisation
antibiotics in infected
```
114
treatment if the infected diabetic foot ulcer does not heal
amputation
115
what increases the likelihood of infection in diabetic foot ulcers
poorly controlled diabetes impairs the function of polymorphonuclear leukocytes leading to an increased susceptibility of infections
116
what are the different hormone classes
peptide
amine
cholesterol derivatives and steroids
117
how are peptide hormones transported
water soluble, unbound
118
how to peptide hormones bind
cell-surface receptor
119
action of steroid hormones
1. diffuse through plasma membrane (because they are lipid soluble)
2. steroid hormone binds to receptors
3. receptor-hormone complex enters the nucleus
4. receptor hormone complex binds to glucocorticoid response elements
5. binding initiates transcription of gene to mRNA
6. mRNA directs protein synthesis
120
3 hormone receptor locations
cell membrane
cytoplasm
nuclear receptor family
121
what are the three releasing factors (stimuli) that control hormone secretion
humoral stimulus : hormone release caused by altered levels of certain ions or nutrients
neural stimulus : hormone release caused by neural input
hormonal stimulus : hormone release caused by another hormone release (e.g tropic hormone)
122
location of the pituitary gland
bottom of the brain
sits on top of the sella turcica of the sphenoid bone
hypothalamus sits on top of the pituitary
123
what connects the hypothalamus to the pituitary gland
pituitary stalk / infundibulum
124
what are the 6 hormones secreted by the anterior pituitary gland
1. adrenocorticotropic hormone (ACTH)
2. Thyroid stimulating hormone
3. Growth hormone
4. Luteinizing hormone
5. Follice stimulating hormone
6. Prolactin
125
what are the two hormones stored in the posterior pituitary gland
1. Vasopressin
| 2. Oxytocin
126
what are the three distinct layers of the adrenal gland and what hormone do they secrete
1. zona glomerulosa : mineralcorticoids (aldosterone)
2. zona fasciculata : glucocorticoids (cortisol)
3. zona reticularis : androgens
127
what are the classes of BMI
```
< 18.5 : underweight
18.5-24.9 : normal
25.0 - 29.9 : overweight
30.0 - 39.9 : obese
> 40 : morbidly obese
```
128
what is the process of food intake
- take in food
- energy balance increases
- fat stores increase
- insulin and leptin are released
- these act on the CNS (catabolic effect to increase metabolic activity, increase physical activity and decrease food uptake)
- if we lose energy the opposite happens
- leptin and insulin act on the CNS (anabolic which decreases energy expenditure and increase food uptake)
129
what is satiety
feeling of fullness, the disappearance of appetite after a meal
130
satiety cascade
1. at the time we should be eating we start to have expectations. smell food and see food. increases satiety
2. start eating because you are hungry and start to become satiated and appetite goes away
3. food goes down into the mouth and down stomach. stretch receptors and glucose in stomach. there is feedback on the brain to tell brain that you are getting full
4. stop eating
131
where is the satiety centre of the brain located
ventromedial hypothalamic nucleus
132
hormone that is secreted in the hypothalamus that increases appetite
neuropeptide Y
133
three main hormones that regulate appetite
```
leptin (expressed in white fat)
peptide YY (SI, pancreas, colon)
cholecystokinin (duodenum)
```
134
action of leptin
binds to leptin receptor and switches off appetite
135
action of peptide YY
inhibits gastric motility and reduces appetite by binding to NPY receptors
136
action of cholecystokinin
binds to receptors in the pyloric sphincter to delay gastric emptying, causes gall bladder contraction and insulin release
137
what are the two acute metabolic emergencies caused by untreated diabetes mellitus
diabetic ketoacidosis
| hyperosmolar coma
138
when does ketogenesis occur
In the place of carbohydate shortages when there are high rates of fatty acid oxidation and large amounts of acetyl CoA are generated that exceeds the capacity of the Kreb's cycle is when ketone formation occurs
139
pathology of diabetic ketoacidosis
occurs in untreated insulin dependent diabetes
1. reduced supply of glucose to cells caused by a significant decline in circulating insulin (pushes body into starvation like state)
2. means there is uncontrollable lipolysis and then an increase in production of free fatty acids
3. increase in fatty acid oxidation
4. increased production of acetyl-CoA leads to ketone body production that exceeds the ability of peripheral tissue to oxidize them
5. ketone bodies are a relatively strong acid and their increase in concentration lowers the pH of the blood
140
main consequence of the acidification of the blood caused by increased concentration of ketone bodies
impairs the ability of haemoglobin to bind to oxygen
141
risk factors for developing ketoacidosis
```
untreated diabetes
stopping insulin therapy
infection
surgery
pancreatitis
```
142
Clinical presentation of diabetic ketoacidosis
```
gradual drowsiness
vomiting
dehydration
ketotic breath
Kussmaul's breathing (deep, rapid breathing as a compensatory mechanism)
```
143
Tests for diabetic ketoacidosis
ECG, Chest X-ray
Urine : dipstick and microscopy culture and sensitivity
Blood : capillary and lab glucose, ketones, pH, U&Es, HCO3-, FBC
144
diagnosis of diabetic ketoacidosis
1. Acidaemia (venous blood pH < 7.3)
2. Hyperglycaemia (blood glucose > 11.0mmol/L) or have known DM
3. Ketonaemia (>3.0mmol/L)
145
Treatment of diabetic ketoacidosis
1. Immediate ABCs assessment
2. Replace fluid loss with 0.9% saline IL over 1 hour
3. Replace deficient insulin
4. Give insulin with glucose to prevent hypoglycaemia
5. Restore electrolyte loss and assess the need for potassium
146
Complications of management of ketoacidosis
cerebral oedema
hypokalaemia
coma
147
why do you get cerebral oedema in diabetic ketoacidosis
The osmolar gradient caused by the high blood glucose results in water shift from the intracelluar fluid (ICF) to the extracellular fluid (ECF) space
148
prevention of diabetic ketoacidosis
talk to the patient and evaluate compliance and educate about triggers
149
what is hyperosmolar hyperglycaemic state
hyperglycaemia causes an osmotic diuresis (increased urine) with hyperosmolarity leading to an osmotic shift of water into the intravascular compartment resulting in severe intracellular dehydration
150
is the ketogenesis in hyperosmolar hyperglycaemic state
No
insulin levels are reduced but still sufficient to inhibit hepatic ketogenesis
So no acidosis is either pH > 7.3
151
who is most likely to develop hyperosmolar hyperglycaemic state
older type 2 diabetic patients
152
risk factors for developing hyperosmolar hyperglycaemic state
infection - particularly pneumonia
| inadequate insulin or oral antidiabetic therapy
153
symptoms of hyperosmolar hyperglycaemic state
early symptoms of generalised weakness, leg cramps or visual impairment
focal neurological symptoms e.g weakness
dehydration (dry mouth, decreased skin turgor or sunken eyes)
154
signs of hyperosmolar hyperglycaemic state
severe dehydration (dry mouth, decreased skin turgor or sunken eyes)
THREE CHARACTERISTIC FEATURES
1. Hypovolaemia
2. Hyperglycaemia (glucose > 30.0 mmol/L)
3. Hyperosmolality (effective serum osmolality > 320mmol/kg)
155
Diagnosis of hyperosmolar hyperglycaemic state
1. Hypovolaemia
2. Hyperglycaemia (glucose > 30.0 mmol/L)
3. Hyperosmolality (effective serum osmolality > 320mmol/kg)
urine dipstick shows heavy glycosuria
total body K+ is low as a result of osmotic diuresis
156
treatment goals of hyperosmolar hyperglycaemic state
normalise osmolality
replace fluid and electrolyte loss
normalise blood glucose
157
the treatment for hyperosmolar hyperglycaemic state
give low dose IV insulin
| fluid replacement with 0.9% saline to restore circulating volume and reverse dehydration
158
what happens to dietary iodide
oxidised to iodine in the thyroid gland by the enzyme thyroid peroxidase
iodine is then used to produced T4 and T3
159
which is the more potent thyroid hormone produced
T3
| T4 is considered to be a prohormone
160
how does T3 and T4 travel in the plasma
it is protein bound to thyroxine-binding globulin
161
what does the free T3 and T4 do
free T3 and T4 are considered to be active and increase cell metabolism via nuclear receptors
162
what is the thyroid pituitary axis
- hypothalamus secretes Thyrotropin-releasing hormone
- TRH stimulates the production of thyroid stimulating hormone from the anterior pituitary gland
- TSH increases production and release of T4 and T3 from the thyroid which both exert a negative feedback effect on TSH and TRH production
163
What are the three types of clinical thyroid disease
Secretory malfunction : hyper and hypothyroidism
Swelling of the entire gland : goitre
Solitary mass : 1 large nodule in a nodular goitre, adenoma or carcinoma
164
what is hyperthyroidism
disease of which there are excess thyroid hormones circulating in the blood
165
Symptoms of hyperthyroidism
```
diarrhoea
weight loss
increased appetite
sweats
heat intolerance
palpitations
tremor
irritability
oligomenorrhea
anxiety
```
166
what is oligomenorrhea
infrequent periods
167
cause of diarrhoea as a symptom of hyperthyroidism
increased effectiveness of the bowel
168
cause of weight loss as a symptom of hyperthyroidism
muscle breakdown
169
actual names of T3 and T4
thyroxine (T4) and triiodothyronine (T3)
170
what do the thyroid hormones do (basic)
influence the metabolism of your body cells
171
Clinical signs of hyperthyroidism
```
Fast/irregular pulse
Warm, moist skin
Fine tremor
Palmar erythema (redness to both palms)
thin hair
lid lag : eyelid lags behind the eye's descent as patient watches your finger descend slowly
lid retraction : stare
```
172
specific clinical signs of Grave's disease
Exophthalmos : bulging of the eye anteriorly out of the orbit
pretibial myxoedema : localised lesions of the skin resulting from the deposition of hyaluronic acid
thyroid acropachy (rare) : clubbing, painful finger and toe swelling.
173
what causes exophthalmos in Grave's disease
infiltration of lymphocytes into orbital tissue stimulates the release of cytokines
Cytokines promote the release of mucopolysaccharides from fibroblasts
Resulting hyperosmotic shift leads to oedema of the orbital fat and extraocular muscles
Eyeball is forced anteriorly
174
how many people with Grave's exhibit exophthalmos
25-30%
175
Investigations of hyperthyroidism
```
thyroid function test to confirm biochemical hyperthyroidism
Clinical history (physical signs are usually sufficient for diagnosis)
Supporting tests
```
176
Tests for hyperthyroidism and results
primary hyperthyroidism : increased free T3 and T4 and suppressed TSH
secondary hyperthyroidism (e.g adenoma) : increased free T4 and T3 but there is an inappropriate high TSH
Thyroid antibodies : TPO, Tg and TRAb
Isotope uptake scan
177
what are the thyroid antibodies
TPO : antithyroid peroxidase antibody
Tg : antithyroglobulin antibody
TRAb : TSH receptor antibodies
178
Commonest cause of hyperthyroidism
Grave's disease
179
Pathogenesis of Grave's disease
production of an autoantibody of the IgG class which binds and activates G-protein coupled receptors which cause smooth thyroid enlargement and increased hormone production (especially T3) and react with orbital autoantigens.
180
In Grave's disease can the autoantibodies cross the placenta
yes
181
Risk factors for developing Grave's disease
Genetic : HLA-DR3 and female
Environmental : smoking, diet, infection
Postpartum
Associated with other autoimmune conditions : T1DM, addison's, vitiligo
182
Causes for Hyperthyroidism
Grave's disease
Toxic multinodular goitre
Toxic, functioning adenoma
Exogenous : iodine excess (food contamination, contrast media (can cause thyroid storm if patient is already hyperthyroid))
183
How does toxic multinodular goitre cause hyperthyroidism
1 or 2 nodules in a goitre may develop hypersecretory activity
Elderly and iodine deficient areas (derbyshire neck)
184
How does a toxic functioning adenoma cause hyperthyroidism
solitary nodule produces T3 and T4
| less than 1% of adenomas
185
Three ways can treat hyperthyroidism and the order you would try
1. Drugs
2. Radioiodine
3. Surgery
186
What is the drug regime in hyperthyroidism
1. Beta-blockers to rapidly control symptoms
2. Antithyroid medication - CARBIMAZOLE
- titration regime for 12-18 months
- block and replace - give carbimazole to suppress thyroid function + thyroxine replacement to restore to euthyroid state
187
how does carbimazole work
inhibits conversion of T4 to T3
188
how many patients will relapse on the drug treatment for hyperthyroidism
approx 50%
| usually younger men than smoke
189
what is the next step if there is a sub-optimal response to the drug treatment in hyperthyroidism
Radioiodine
| Surgery (if there is a sub-optimal response to radioiodine or patient is pregnant)
190
How does radioiodine work in hyperthyroidism
radioactive iodine is given to the patient as a drink and is actively transported into thyroid follicular cells
Causes necrosis of follicular cells
191
What surgery for hyperthyroidism
partial or sub total thyroidectomy
192
side effects of of carbimazole
rash, hepatitis, thrombocytopenia, vasculitis
| can cause bone marrow suppression and agranulocytosis in 0.5% of patients
193
Complications of hyperthyroidism
heart failure
angina
AF
osteoporosis
194
symptoms of hypothyroidism
```
tired
lethargic
cold intolerance
increased weight
constipation
Menorrhagia
Hoarse voice
Decreased memory and cognition
Muscle cramps
Weakness
Dry skin
```
195
Clinical signs of hypothyroidism
```
BRADYCARDIC
Bradycardic
Reflexes relax slowly
Ataxia
Dry thin hair
Yawning
Cold hands
Ascites
Round puffy face - myxodermic face
Defeated demeanor
Immobile (muscle weakness)
```
196
Diagnosis for hypothyroidism
Thyroid function test
Primary hypothyroidism : low T4 and T3. TSH is high.
Secondary hypothyroidism : reduced T4 and T3. TSH may be inappropriately low
Increased cholesterol and triglyceride
197
Causes of primary hypothyroidism
```
Hashimoto's thyroiditis
Atrophic thyroiditis
Iodine deficiency
Post radio iodine treatment
Drug induced (amiodarone, lithium)
```
198
what antibodies can be detected in Hashimoto's thyroiditis
antithyroid peroxidase
| antithyroglobulin
199
Treatment of hypothyroidism
synthetic L-thyroxine (T4)
200
why are the symptoms of thyroid disease so various and subtle
almost all cell nuclei have receptors showing a high affinity for T3
201
which tumours of the thyroid are treatable and usually curable?
differentiated tumours
| papillary / follicular
202
which tumours of the thyroid are less common, more aggressive and have a much poorer prognosis?
poorly differentiated
| medullary / anaplastic
203
how to diagnose a thyroid tumour?
ultrasound is the first line diagnostic procedure
fine needle aspiration cytology
thyroid functioning test
204
most common cancer of the thyroid gland
papillary adenocarcinoma
205
risk factors for thyroid cancers
```
exposure to ionising radiation
family history
female
asian
obesity
```
206
presentation of thyroid cancer
thyroid nodule
| hard and fixed nodules are more suggestive of malignancy
207
red flags in thyroid nodule presentation that could be cancer
family history
history of previous irradiation
child patient
unexplained hoarseness associated with goitre
painless thyroid mass enlarging rapidly over a period of weeks
palpable cervical lymphadenopathy
208
causes of pituitary disease
```
benign pituitary adenoma
craniopharyngioma
trauma
apoplexy
sheehans
```
209
what effects do pituitary tumours have
- cause pressure on local structures
- put pressure on the pituitary gland
- may be a functioning pituitary tumour
210
complication of a pituitary tumour causing pressure on local structures
can cause bitemporal hemianopia due to compression at the optic chiasm
patients have early desaturation to red when there is increased pressure on the optic chiasm (test using red needle)
211
what happens if there is a tumour that is putting pressure on the pituitary gland
lack of function of the pituitary gland
| hypopituitary man
212
signs of hypopituitary man
pale (loss of testosterone)
no body hair (loss of testosterone)
centrally obese (loss of function of growth hormone)
213
Examples of conditions caused by a functioning pituitary tumour
Cushing's
Acromegaly
Prolactinoma
214
what is Cushing's disease (definition)
chronic, excessive and inappropriate elevated levels of circulating plasma glucocorticoids (cortisol)
215
what is the difference between cushing's disease and cushing's syndrome
cushing's disease : make too much of ACTH hormone which causes adrenal glands to make more cortisol
cushing's syndrome : adrenal glands have a tumour making too much cortisol
216
why is cushing's disease important to spot in children
it is virtually the only disease that can make a child put on weight but not grow
217
causes of Cushing's
Tumour of the pituitary gland making too much ACTH
Ectopic tumour causing increased ACTH secretion
Adrenal tumour making too much cortisol (syndrome)
Exogenous steroids
218
Pathophysiology of Cushing's disease
Tumour in anterior pituitary gland causes an increase of ACTH to be released
Increased ACTH in the body which acts on the adrenal gland to cause an increase in cortisol
Cortisol acts on the hypothalamus and pituitary gland to suppress ACTH and decreased production of corticotropin releasing hormone
219
Pathophysiology in Cushing's syndrome
Tumour in the adrenal gland causing increased cortisol production
Low ACTH and CRH
220
Symptoms of Cushing's
```
Fat
- increased fat
- central obesity
- moon face
- weight gain
- buffalo hump
Protein
- catabolism
- muscle weakness and wasting
- thin skin (striae on abdomen) + easy bruising
Androgenic
- Hirsutism
- Acne
```
221
what can also happen if there is increased cortisol in the body
immunosuppression
222
Clinical features of Cushing's
1. carbohydrate metabolism - impaired glucose tolerance
2. electrolyte disturbance - sodium retention, hypertension
3. immune suppression
4. central effects - malaise, depression
5. suppressed gonadal function - oligo/amenorrhoea, impotence, loss of libido
223
4 important features of Cushing's
Think skin
Easy bruising
Decreased linear growth in children
Weakness
224
2 steps to diagnosing Cushing's
1. need to confirm if the patient has increased cortisol
| 2. investigation into the cause of excess cortisol
225
What are the main screening tests to detect if a patient has increased serum cortisol
1. Urinary free cortisol test
2. Low dose dexamethasone suppression tests
3. Late night/midnight salivary cortisol
4. Late night/midnight plasma serum cortisol
226
Why would you have an increased urinary cortisol in Cushing's
Cortisol is bound to cortisol binding globulin and albumin. If these carriers are saturated then the cortisol can spill out into the kidneys so need to measure the amount of cortisol in the urine
227
What is a low dose dexamethasone suppression test
Giving a synthetic steroid that is trying to suppress the tumour
Taken at 11pm then cortisol measurement at 8am next day
Serum cortisol > 50nM (normal)
228
Why do you take a late night/midnight salivary cortisol
In Cushing's you lose the normal circadian rhythm
Normally cortisol levels are very low in the night
In Cushing's the levels are elevated
229
Results that suggest Cushing's disease in a late night/midnight serum cortisol
Sleeping > 50nM
230
If you get an abnormal result for cortisol and it is raised what is the next investigation
Measure plasma ACTH
| This determines if it is ACTH independent or ACTH dependent Cushing's syndrome
231
You find that it is ACTH independent Cushing's syndrome, what are the next investigations for diagnosis ?
Adrenal imaging with CT
- Adrenal lesion --> adenoma or carcinoma
- No adrenal lesion --> Exogenous steroids, PPNAD
232
You find that it is ACTH dependent Cushing's syndrome what are the next investigations for diagnosis?
Pituitary MRI and CRH test (injection of CRH)
1. Adenoma + positive CRH response + suppression on high dose dexamethasone suppression test --> CUSHING'S DISEASE
2. Small/no adenoma + No ACTH gradient --> CT/MRI thorax + abdomen --> Ectopic ACTH
233
what is the difference between low dose dexamethasone and high dose dexamethasone suppression tests
An abnormal response to the low-dose test may mean that you have abnormal release of cortisol (Cushing syndrome). The high-dose test can help tell a pituitary cause (Cushing disease) from other causes.
234
Results of the dexamethasone suppression tests in Cushing's disease.
Low-dose test -- no decrease in blood cortisol
| High-dose test -- expected decrease in blood cortisol
235
Management of Cushing's disease
Transsphenoidal surgery + radiotherapy (adjuvant therapy)
236
Management of ectopic tumour, adrenal adenoma/carcioma causing Cushing's?
Adrenalectomy
237
Potetial complication from an adrenalectomy?
Nelson's syndrome
| - enlargement of an ACTH producing tumour in pituitary gland following surgical removal of the adrenal glands
238
Pathogenesis of acromegaly
Increased secretion of growth hormone from a pituitary tumour
Growth hormone stimulates bone and soft tissue growth through increased secretion of insulin-like growth factor-1 from the liver
It is characterised by ongoing, inappropriate high levels of growth hormone
239
When does gigantism occur?
If agromegaly occurs before the fusion of the epiphysis
240
symptoms of acromegaly
- acroparesthesia (tingling, prickling, burning, or numb feeling in the hands or feet.)
- changes in facial features (thickening of the jaw and nasal bridge)
- larger hands/feet (increase in ring size/shoe size)
- amenorrhoea
- headache (change in circulation of IGF-1 in CSF)
- excessive sweating
- Backache
- snoring
241
Signs of acromegaly
- increased hand, foot and jaw growth
- wide nose
- macroglossia (unusually large tongue)
- puffy lids, eyelids and skin
- skin darkening
- obstructive sleep apnoea
242
Complications and comorbidities associated with acromegaly
impaired glucose tolerance
vascular changes - increased risk of IHD and stroke
Arthritis
243
Investigations to diagnose acromegaly
1. Randome Growth Hormone and IGF-1
- if less than 0.4ng/ml = excluded
- if abnormal go to step 2
2. 75mg glucose tolerance test
- if the lowest GH value during OGTT is above 1ug/L then agromegaly is confirmed
244
Why do we do a OGTT in acromegaly testing
normally GH secretion is inhibited by high glucose and GH is hardly detectable. In agromegaly GH fails to be suppressed
245
What is the three line strategy for the treatment of acromegaly?
surgery
somatostatin analogues
pegvisomant
246
what is surgical management of acromegaly (first line treatment)
transsphenoidal excision of the pituitary tumour
success of surgery is dependent on the size of the tumour (microadenomas have a higher cure rate) and the skill of the surgeon
247
complication of pituitary surgery in acromegaly
hypopituitarism
248
what is the second line treatment for acromegaly
somatostain agonists control GH and IGF-1
249
examples of somatostatin analogues
octreotide or lanreotide
250
what is the third line treatment for acromegaly
pegvisomant
251
mechanism of action of pegvisomant
growth hormone competitive antagonist that binds to growth hormone receptors and inhibits dimerization of GH
act at the liver
used if resistant or intolerant to SSA
252
production of prolactin
prolactin is produced in the lactotroph cells of the anterior pituitary gland. production is stimulated by : dopamine receptor antagonists, suckling infant,
253
what inhibits prolactin production
dopamine!
dopamine binds to type 2 dopamine receptors that are functionally linked to membrane channels and G proteins which suppress the high intrinsic secretory activity and lactrotroph proliferation.
this is tonic inhibition
254
cause of prolactinoma
lactotroph cell benign tumour of the pituitary
255
clinical features of prolactinoma
```
galactorrhoea - excessive / inappropriate secretion of breast milk
menstrual irregularity
infertility
low libido
erectile dysfunction
local effects of tumour
```
256
when should you not measure a patient's prolactin
when the patient is on antidopaminergic drugs
| need to do a careful drug history
257
Management of prolactinoma
```
Dopamine agonists (cabergoline, bromocriptine)
shrinks the tumours
```
258
Possible complications of prolactinoma
osteoporosis
| reduced fertility
259
what is conn's syndrome
rare health problem that occurs when the adrenal glands make too much aldosterone
260
what is conn's syndrome also known as
primary hyperaldosteronism
261
pathophysiolgy of conn's syndrome
excess production of aldosterone, independent of the RAAS system causing increased sodium and water retention and decreased renin release
262
symptoms of conn's syndrome
asymptomatic or signs of hypokalaemia, weakness, cramps, paraesthesiae, polyuria, polydipsia
263
causes of conn's syndrome
solitary aldosterone producing adenoma
| conn's is the cause for 60% of primary hyperaldosteronisms
264
Tests for conn's syndrome
U&E
Renin
Aldosterone
CT/MRI maybe to find the site of the adenoma
If patient has an adrenal mass - will have adrenal vein sampling
265
Treatment for conn's syndrome
laprascopic adrenalectomy
266
briefly describe the hypothalamo-pituitary adrenal axis
1. hypothalamus releases corticotropin releasing hormone which acts on the anterior pituitary gland
2. anterior pituitary gland releases ACTH that enters the circulation
3. ACTH travels to the adrenal cortex and stimulates it to secrete: aldosterone, cortisol and androgens
4. increase in cortisol in the circulation has a negative feedback on the hypothalamus
267
what is the function of aldosterone
increases sodium and water retention resulting in increase in blood pressure
268
what is addison's disease
primary adrenal cortex insufficiency
269
biggest causes of addison's disease
autoantibodies being produced against adrenal cortex cells +/- autoantibodies against the 21-hydroxylase enzyme.
Autoimmune attack causes damage and leads to cortisol and aldosterone deficiency
decrease in minceralcorticoids leads to hypotension and tachycardia
270
other causes of addison's disease
```
infection - TB is most common worldwide
adrenal cortex malignancy
secondary malignancy of the adrenal cortex from mets
lymphoma
infiltration diseases : amyloidosis
Iatrogenic causes
```
271
symptoms of addison's disease
```
tiredness,
dizziness,
weight loss
abdominal pain
decreased libido (women only)
nausea + vomiting
lean
arthralgia and myalgia
```
272
signs of addison's disease
```
low grade fever
dehydration
postural hypotension
tachycardia
pigmentation and pallor - buccal mucosa
generalised hyperpigmentation
```
Need a high level of suspicion for diagnosis!! Think of addison's in all with unexplained abdominal pain or vomiting
273
Investigations results of addison's disease (biochemistry)
Biochemistry
- decreased Na+
- Increased K+
- decreased glucose due to decreased cortisol
- eosinophilia
- increased Ca2+
274
Tests to do when investigating someone with addison's disease
- Synacthen test
- 9am ACTH
- 21-hydroxylase adrenal autoantibodies
- plasma renin and aldosterone to assess mineralcorticoid status
275
what is the synacthen test (addison's)
do plasma cortisol before and 1/2 hour after tetracosacride
| Addison's is excluded if 30min cortisol is > 550nmol/L
276
Results of a 9am ACTH test to suggest addison's disease
cortisol is low
| ACTH is innappropriately high
277
Treatment for Addison's disease
Hydrocortisone 2 or 3 times daily
| replace aldosterone with fludrocortisone
278
what are the sick day rules
what actions patients who are on steroids need to take during illness and stressful situations
- if unwell - double the dose
- if vomiting or increasingly unwell take emergency injection of hydrocortisone IM
279
what is secondary adrenal insufficiency
inadequate pituitary or hypothalamic stimulation of the adrenal glands
No autoantibodies
280
what are the two types of secondary adrenal insufficiency
1. diseases that cause a total absence of ACTH --> destruction of hypothalamus/pituitary gland (e.g pituitary tumours, surgery to remove a pituitary tumour, radiation therapy to the pituitary)
2. diseases that cause a suppression of ACTH
281
what is the most common cause of secondary adrenal insufficiency
iatrogenic due to long term steroid therapy leading to suppression of the pituitary adrenal axis. Only becomes apparent on the withdrawal of steroids
282
symptoms of secondary adrenal insufficiency
```
severe fatigue
loss of appetite
weight loss
nausea & vomiting
muscle weakness
```
283
differences between Addison's disease and secondary adrenal insufficiency
aldosterone is usually present, so low blood pressure and muscle spasms are not as likely
no hyperpigmentation
284
diagnosis and tests in secondary adrenal insufficiency
blood tests - normal K+, blood sugar may be low but not always, FBC is usually normal
tests are usually same as addison's but there are some differences
- ACTH are low or normal
- Plasma renin and aldosterone levels are usually unaffected
-insulin tolerance test is occasionally used to confirm a diagnosis
285
treatment for secondary adrenal insufficiency
hydrocortisone
286
what is the common presentation of adrenal crisis
```
hypotension and cardiovascular collapse
fatigue
fever
hypoglycaemia
hyponatraemia and hyperkalaemia
```
287
treatment for adrenal crisis
Bloods if possible for ACTH and cortisol
Hydrocortisone immediately IV or IM
fluids
288
define hyperkalaemia
plasma potassium in excess of 5.5mmol/L
289
what is regarded as severe hyperkalaemia
plasma potassium > 6.5 mmol/L
290
Causes of hyperkalaemia
Renal - AKI, CKD, ACE inhibitors
Increased circulation of potassium - exogenous or endogenous (massive tissue damage, fresh water drowning)
Shift from the intracellular to extracellular space (acidosis e.g DKA)
291
reasons why a lab result for potassium showing hyperkalaemia may not be valid?
tourniquet has been on for a prolonged amount of time
difficulting collecting sample
length of storage
test tube haemolysis
292
symptoms of hyperkalaemia
weakness, fatigue, may present with muscular paralysis or SOB or palpitations
293
signs of hyperkalaemia
occasional bradycardia due to heart block
tachypnoea from resp muscle weakness
muscle weakness and flaccid paralysis
294
concerning signs and symptoms in hyperkalaemia
```
fast irregular pulse
chest pain
weakness
palpitations
light headedness
```
295
investigations for hyperkalaemia
blood tests
- urea
- other electrolytes
- creatinine
- ABG - looking for metabolic acidosis
296
ECG changes in hyperkalaemia
- tall tented t wave
- longer PR interval
- reduced or no p waves
- widening of QRS complex
usually only seen in severe cases
297
Management of hyperkalaemia
EMERGENCY
- ABCDE
- ABG
- ECG
- full history including drug history
- Reduce the potassium
298
Treatment of hyperkalaemia
- give calcium gluconate to protect the cardiac membrane if there are ECG changes
- Insulin-dextrose infusion
299
define hypokalaemia
serum concentration of potassium < 3.5 mmol/L
300
3 causes of hypokalaemia
- severe vomiting
- diarrhoea
- Cushing's syndrome/steroids
- diuretic therapy
- pyloric stenosis
- Conn's syndrome
301
what is hypokalaemia often accompanied by
metabolic alkalosis due to hydrogen ion shift into the intracellular compartment
302
presentation of hypokalaemia
```
mild cases tend to be asymptomatic
in more severe cases:
- lassitude (lack of energy)
- generalised weakness and muscle pain
- constipation
- cardiac dysrhythmias
```
303
investigations of hypokalaemia
Blood test
| ECG
304
what ECG changes can be picked up in hypokalaemia
small/inverted T waves
long PR interval
depressed ST segments
305
Treatment of mild hypokalaemia
oral K+ supplement
306
treatment of severe hypokalaemia
IV potassium
give cautiously!
severe is defined as serum potassium < 2.5 mmol/L
307
what is the equation for plasma osmolality
plasma osmolality = (2x [Na+]) + glucose + urea
308
define hyponatraemia
low sodium concentration in the blood
depends on both the amount of Na+ and water present in the circulation
serum sodium < 135mmol/L
309
what do the symptoms of hyponatraemia depend on
the onset of symptoms
| the quicker the onset the greater the symptoms
310
tests when hyponatraemia presents
plasma osmolality
urine osmolality
plasma glucose
urine sodium
311
why are there different approaches in acute vs chronic hyponatraeima
acute - rapid correction
| chronic - CNS adapts so the correction must be slow
312
what is syndrome of inappropriate secretion of ADH
excessive secretion of ADH from the posterior pituitary gland or another source
by increasing water retention, ADH causes dilution of the blood and decreases the concentration of solutes
313
what is the normal physiology of ADH
1. ADH produced by hypothalamus in response to increased serum osmolality detected by the osmoreceptors
2. ADH is transported to the posterior pituitary gland
3. ADH is released into the circulation
4. ADH travels to kidneys and binds to ADH receptors on the CD
5. binding of ADH causes aquaporin-2 channels to move from the cytoplasm into the apical membrane of the tubules
6. water reabsorption out of the collecting ducts back into the blood stream
7. results in a decrease in volume and increase in osmolality of the urine produced
8. reduction in serum osmolality
9. reduction in serum osmolality detected by the hypothalamus and results in decreased production of ADH (negative feedback)
314
pathogenesis of syndrome of inappropriate secretion of ADH
lack of the negative feedback mechanism
inability to reduce or stop ADH production
leads to abnormally low levels of serum sodium (due to the excess water resorption) and relatively high levels of urine sodium
315
causes of syndrome of inappropriate secretion of ADH
```
Malignancy
- small cell lung cancer
CNS disorders
- meningitis
- subarachnoid haemorrhage
Chest disease
- TB
- atypical pneumonia
Endocrine disease
- hypothyroidism
Drugs
- carbamazepine
- opiates
-SSRIs
```
316
3 symptoms of SIADH (mild)
```
nausea
vomiting
headache
anorexia
lethargy
```
317
3 symptoms of SIADH (moderate)
muscle cramps
weakness
confusion
318
3 symptoms of SIADH (severe)
drowsiness
seizures
coma
319
why do some chronically hyponatremic patients have very low serum sodium concentrations but are completely asymptomatic ?
Cerebral adaptation
1. ECF hypoosmolality
2. water moves into the brain in response to osmotic gradients producing brain oedema
3. in response to swelling the brain expels electrolytes and organic osmolytes
4. water loss accompanies the loss of these solutes, reduing swelling
5. if hypo-osmolality is sustained, brain volume normalises and the brain becomes adapted to hyponatraemia
320
3 signs of SIADH
```
decreased levels of consciousness
cognitive impairment
brain stem herniation (severe, can result in coma/resp arrest)
focal or generalised seizures
hypervolaemia
- pulmonary oedema
- peripheral oedema
- raised jugular venous pressure
```
321
investigations in SIADH
- fluid status (in SIADH, patient is either euvolemic or hypervolaemic)
- serum sodium
- serum potassium
- urine osmolality (will be high it is the excess ADH causing water retention!! it is usually low if serum osmolality is low)
322
what does there need to be to diagnose SIADH
- no dehydration
- not oedematous
- concentrated urine
- hyponatraemia
- low plasma osmolality
323
management of SIADH
- treat the underlying cause
- fluid restriction used to increase serum sodium concentrations
- demeclocycline
- replace sodium (IV or orally)
- vasopressin receptor antagonist (but v expensive)
324
complication of replacing sodium concentration too quickly in patients with hyponatraemia
central pontine myelinolysis (permanent damage to the myelin sheath in the brain stem)
325
definition of hypernatremia
serum sodium concentration of > 145mmol/L
326
causes of hypernatremia
dehydration (inadequate water intake, DI, thirst impairment)
hypotonic fluid loss (dermal losses e.g burns, GI losses e.g D&;V, urinary losses e.g diuretics)
hypertonic sodium gain (iatrogenic e.g tube feeding, excess salt ingestion)
327
5 Signs and symptoms of hypernatremia
```
Lethargy
Thirst
Polydipsia
Polyuria
Weakness
Irritability
Confusion
Fits
Coma
Signs of dehydration
```
328
Investigations for hypernatremia
Check serum sodium, potassium, urea, creatinine etc.
329
Lab results for hypernatremia
- increased Na+
- increased packed cell volume
- increased albumin concentration
- increased urea
330
Management for hypernatremia
Treat any underlying disorder if possible
| Give water to slowly replace dehydration (orally if possible)
331
what is diabetes insipidus
the passage of large volumes of dilute urine (more than 3L a day) due to impaired water reabsorption by the kidney, because of reduced ADH secretion from the posterior pituitary (cranial DI) or impaired response of the kidney to ADH (nephrogenic DI)
332
what is cranial diabetes insipidus
occurs due to decreased circulating levels of vasopressin
333
what is nephrogenic diabetes insipidus
anything that interferes with the binding of vasopressin to their receptors or damages the kidney leading to an impaired response by the kidney to ADH
334
3 acquired causes of cranial diabetes insipidus
```
idiopathic
tumours : craniopharyngioma, germinoma
Trauma to hypothalamus or posterior pituitary
Neurosurgery
Infections : meningitis
Vascular - Sheenan's sickle cell
```
335
name a genetic cause of cranial diabetes insipidus
Wolfram syndrome
336
name a familial cause of nephrogenic diabetes insipidus
X linked, V2 receptor defect
| Autosomal recessive : aquaporin 2 defect
337
name 3 acquired causes of nephrogenic diabetes insipidus
osmotic diuresis
Drugs (lithium, tetracycline)
Chronic renal failure
post-obstructive uropathy
338
Symptoms of diabetes insipidus
excessive urination, polyuria > 3L/day
excessive thirst esp for ice water, polydipsia
nocturia
dehydration -headache/dizziness/dry mouth
339
signs of diabetes insipidus
hypotension
dilute urine
reduced capillary fill time
dehydration
340
Investigations and tests in diabetes insipidus
- FLUID DEPRIVATION TEST
- measure urine output
- glucose test to exclude DM - dipstick urine
- U&Es
- serum and urine osmolalities
341
when should you do the fluid deprivation test
for diagnosis of diabetes insipidus
| only do when urine output has been confirmed as over 3L a day !
342
what does the fluid deprivation test test for
tests the ability of the kidneys to concentrate urine for diagnosis of DI and then to localise the cause
343
outline the two steps of the fluid deprivation test
STAGE 1
- Empty bladder, no drinks, only dry food
- weigh hourly
- if more than 3% of weight loss during test, order serum osmolality if more than 300mOsm/kg --> stage 2
STAGE 2
- give desmopressin IM
344
how can the fluid deprivation test determine cranial from nephrogenic DI
If after stage 2...
1. urine osmolality increases --> CRANIAL DI because the cause is a lack of vasopressin, so giving the synthetic form normalises the urine osmolality
2. urine osmolality stays same --> NEPHROGENIC DI
kidneys are not able to respond to vasopressin so is unable to respond to the synthetic form
345
Management of cranial DI
MRI of head
Test anterior pituitary function
Give desmopressin
346
management of nephrogenic DI
treat the cause / stop any causative drugs (e.g lithium)
advise patient to maintain adequate fluid intake
correct any metabolic derangements
Bendroflumethiazide can reduce the action of prostaglandins which can inhibit the action of vasopression on the kidneys
347
what is the equation for corrected calcium
corrected calcium = total serum calcium + 0.02 x (40- serum albumin)
348
why do we have to correct calcium when investigating hypocalcaemia
need to establish if it is really hypocalcaemia, apparent hypocalcaemia may be an artefact of hypoalbuminaemia
349
3 causes of hypocalcaemia with increased phosphate
chronic kidney disease
hypoparathyroidism
pseudohypoparathyroidism
350
3 causes of hypocalcaemia with equal or decreased phosphate
vitamin D deficiency
osteomalacia
acute pancreatitis
respiratory alkalosis
351
signs of symptoms of hypocalcaemia
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SPASMOC
Spasms - Trousseau's sign
Paraesthesia
Anxious
Seizures
Muscle tone increases in smooth muscle
Orientation is impaired --> confusion
Chvostek's sign - tap over the facial nerve and look for spasm of facial muscles
```
352
What abnormality would show on an ECG of hypocalacemia
Long QT interval
353
Treatment for mild and severe hypocalcaemia
mild : give calcium and check daily plasma Ca2+
| severe : calcium gluconate IV over 30 mins
354
briefly outline the physiology of calcium homeostasis
- decreased in serum Ca2+
- stimulates an increase in parathyroid hormone
- PTH leads to: bone resorption, and Ca2+ resorption at the kidney and intestine to increase serum calcium
355
what is the set point of ionised calcium
1.1mmol/L
356
2 causes of hypercalcaemia
Malignancy - bone mets, myeloma, lymphoma
| Primary hyperparathyroidism
357
symptoms of hypercalcaemia
bones, stones, moans and psychic groans
- bone ache and pain
- renal stones
- abdominal pain, vomiting, constipation
- confusion
358
aims of the investigations for hypercalcaemia
need to distinguish if it is malignancy or primary hyperparathyroidism
359
what results point towards malignancy as a causes for hypercalcaemia
low PTH
high calcium
low phosphate
PTH is appropriate
360
what results point towards hyperparathyroidism as a causes for hypercalcaemia
PTH is high (inappropriate)
361
treatment of acute hypercalcaemia
correct dehydration
bisphosphonates
(chemo may help in malignancy)
362
What is hyperparathyroidism
high levels of PTH
363
physiology of the parathyroid gland
- 4 parathyroid glands in the 4 corners of the thyroid gland
- chief cells produce PTH in response to low serum ionised calcium conc
- PTH acts to increased to Ca2+ conc by : increasing absorption from the intestine, increasing reabsorption from the kidneys and increasing the osteoclast activity in the bones
364
cause of primary hyperparathyroidism
tumour
| usually solitary benign adenoma
365
presentation of primary hyperparathyroidism
signs and symptoms of hypercalcaemia
| bones, stone, moans and groans
366
what is the PTH and Ca2+ in primary hyperparathyroidism
Increased
367
Treatment of primary hyperparathyroidism
surgical removal of tumour
368
what are the causes of secondary hyperparathyroidism
insufficient vitamin D or chronic renal failure
369
pathogenesis of secondary hyperparathyroidism
reduced absorption of calcium (hypocalcaemia)
| PT glands secrete PTH to compensate
370
PTH and Ca2+ in secondary hyperparathyroidism
PTH : appropriately high
| Ca2+ : decreased or normal
371
treatment for secondary hyperparathyroidism
increase vitamin D
| Kidney transplant
372
what is the pathogenesis of tertiary hyperparathyroidism
secondary continues for a long period of time leading to large hyperplasia of the PT glands
causing hypercalcaemia
373
treatment of tertiary hyperparathyroidism
surgery to remove PT glands
374
PTH and Ca2+ in tertiary hyperparathyroidism
PTH : inappropriately high
| Ca2+ : high
375
what is hypoparathyroidism
state of decreased secretion or activity of PTH leading to decreased blood levels of calcium and increased levels of phosphate
376
3 causes of hypoparathyroidism
1. surgery
2. Di George syndrome
3. Radiation
4. Autoimmune
377
pathophysiology of hypoparathyroidism
decreased PTH
decreased renal calcium reabsorption, increased renal phosphate reabsorption, decreased bone resorption and decreased formation of 1,25(OH)2D
All leads to decreased serum calcium
