Endocrinology - Week 4 Flashcards Preview

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Flashcards in Endocrinology - Week 4 Deck (217)
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1

what contributes to calories in

food and absorption

2

what contributes to calories out

basal metabolic rate, thermogenesis, non purposeful activity, exercise

3

heritability of obesity

40-70%

4

what are the efferents of the hypothalamus

pituitary which goes on to:
gonads - sex steroids
adrenal cortex - cortisol
thyroid - thyroxine
growth hormone

autonomic NS
parasympathetic - insulin
sympathetic - adrenaline

5

what are afferents of the hypothalamus

• Conscious control
• Fatty acids, glucose, hormones
• Leptin
• Ghrelin
• Insulin

6

when is leptin treatment for obesity effective

• Ineffective when leptin is high
o Idiopathic obesity

• Effective when [leptin] is low
o Leptin deficiency (rare)
o Anorexia nervosa
o Lipodystrophy

7

what are the actions of leptin

• Satiety
• Hypothalamic-pituitary-gonadal axis
o Puberty
o Fertility
• Hypothalamic-pituitary-adrenal axis
• Hypothalamic-pituitary-thyroid axis

• Peripheral actions??
o Adipocytes, pancreatic islets, immune cells, …

PROBABLY MOST IMPORTANT IN LOW ENERGY STATES
AS SURVIVAL SIGNAL

8

what are some causes of secondary obesity

• Hypothyroidism
• Cushing’s syndrome - usually iatrogenic
• Hypothalamic disease

• Others
o Drugs (oestrogen, beta blockers, tricyclic antidepressants, sodium valproate)
o Insulinoma, GH deficiency
o Genetic Disorders: e.g. Prader Willi syndrome, Bardet Biedl syndrome, leptin or leptin receptor deficiency, melanocortin 4 receptor defect, POMC deficiency

9

spotting endocrine disorders in obesity History

• Always obese/age of onset?
o Periods regular/ headache/ thirst, polyuria?
o Diet, eating pattern, alcohol, exercise?
o Drugs?
o Complications and effects on lifestyle

• Examination:
o Features of Cushing’s, hypothyroidism, hypothalamic disease, syndromes
o BP

• Investigations:
o TFTs › Blood glucose
o ?o/n dex suppression test

10

why is obesity bad for you

• Breathlessness, Sleep apnoea
• Cancers (breast, endometrium, ovary, colon, gallbladder)
• Gallstones, NAFLD
• Incontinence
• Varicose veins
• Arthritis
• Social & Psychological
• Heart attack
• Hypertension
• Diabetes mellitus
• Infertility & hirsutis

11

describe fat distribution

Fat distribution – Apples and Pears
Central Visceral Android ‘Apple’ HIGH RISK
Peripheral Subcutaneous Gynoid ‘Pear’ LOW RISK

12

what is important about visceral fat

• different metabolism or secretion
• releases direct to liver

13

what is lawrence syndrome

“Lipoatrophic” Diabetes

• Generic IR complications
o Acanthosis nigricans
o Hyperandrogenism
o Female subfertility
o Precocious puberty
o Diabetes mellitus
o Soft tissue overgrowth

• Lipotoxic complications
o Severe dyslipidaemia
o NAFLD, cirrhosis, HCC
o Premature atherosclerosis
o Diabetes mellitus

14

describe adipokines

• Secreted from adipocytes or macrophages in adipose tissue
• Manipulations in mice demonstrate potent effects on insulin sensitivity in other tissues
• Correlated with increased insulin sensitivity in other tissues in humans
• Many candidates published – variable importance in subsequent studies

15

what are the endocrine consequences of obesity

• Altered steroid metabolism in adipose tissue:
o Increased oestrone and oestradiol
 Hirsutism and infertility
 Hormone-sensitive cancers
o increased reactivation of cortisol from cortisone

• Altered substrate flux and adipose inflammation
o Insulin resistance
 Hyperglycaemia
 Dyslipidaemia, Fatty Liver
 Subfertility

• Altered hypothalamic function
o Anovulatory menstrual cycles
 Subfertility

16

describe diabetes and its epidemiology

• Affects 5% of total population
• Affects 10% of people over 65
• Around 3.2 million people are known to have diabetes
• Many people have undiagnosed diabetes
• About 25% require insulin therapy

Diabetes mellitus is a condition associated with an elevated blood glucose. This is a consequence of deficiency of INSULIN, or of its reduced action, or of a combination of both.

17

describe insulin

• Hormone secreted in pancreas (islets)
• Anabolic hormone
• Essential for fuel storage and cell growth
• Promotes uptake of glucose into cells for energy
• Prevents breakdown of fat and protein

18

describe pancreatic cells

Alpha cell Glucagon 11%
Beta cell Insulin 85%
Delta cell Somatostatin 3%
F cell Pancreatic polypeptide 1%

19

describe the structure of insulin

Insulin has an alpha and beta subunit which are linked by disulphide bonds and C-peptide. This is proinsulin. Prior to release by cells, C-peptide is cleaved away to leave insulin and free C-peptide. This is done by b-cell peptidases.

20

how is Insulin Secretion from Beta Cells is Directly Coupled to Glucose Influx

Beta cells have GLUT 2 transporters which are insulin independent and let in glucose purely based on extracellular glucose concentration. This glucose is metabolised by the cell to give ATP. This ATP will inhibit K channels which then don’t pump K out of the cells. This leads to depolarisation of the membrane which in turn leads to voltage gated Ca channels to open and let Ca into the cell. Ca causes exocytosis of insulin granules into the bloodstream.

21

describe insulin release

• Pro-insulin is converted to insulin and C-peptide in equimolar amounts
• In response to ingestion of food, stored insulin is released first, followed by newly synthesised insulin
• This gives a biphasic response of insulin secretion
• C-peptide can be used as a measure of endogenous insulin secretion in people with diabetes

INSULIN from pancreas:
• Secreted into portal vein
• Acts first on LIVER
• Passes through liver into systemic circulation
• Acts on MUSCLE and FAT

22

what are the Principal Actions of Insulin

↑ Glucose uptake in FAT and MUSCLE
↑ Glycogen storage in LIVER and MUSCLE
↑ Amino Acid uptake in MUSCLE
↑ Protein Synthesis
↑ Cell proliferation
↑ Lipogenesis in ADIPOSE TISSUE

↓Apoptosis
↓ Gluconeogenesis from 3-Carbon precursors
↓Ketogenesis (in LIVER)


Insulin Causes Translocation of GLUT 4 to Cell Membranes. This allows insulin-dependent glucose uptake into cells

23

what is the difference between insulin and glucagon

Insulin favours glycogenesis and inhibition of gluconeogenesis

Glucagon favours glycogenolysis and gluconeogenesis

24

what are some 3-carbon precursors

 Alanine (from ingested protein)
 Pyruvate (from muscle protein)
 Lactate (from muscle glycogen)
 Glycerol (from fat)

25

what are the 4 ways of being diagnosed with diabetes

• Fasting plasma glucose > 7.0 mmol/l
• 2hr plasma glucose in OGTT > 11.1 mmol/l
• Random plasma glucose > 11.1 mmol/l
• HbA1c > 48 mmol/mol

• If the patient is asymptomatic, the same test should be repeated to confirm the diagnosis of diabetes
• Do not delay urgent care waiting for a second test

26

describe Glycated Haemoglobin (HbA1c)

• Rate of formation of glycated haemoglobin is directly proportional to ambient blood glucose concentration
• Reflects integrated blood glucose (BG) concentrations during lifespan of erythrocyte (120 days)
• Blood sample can be taken at any time of day, irrespective of food consumption
Normal ≤41 mmol/mol
Pre-diabetes 42-47 mmol/mol
Diabetes ≥ 48mmol/mol

27

Situations where HbA1c should NOT be used as a Diagnostic Test

• Rapid onset of diabetes
– Suspected Type 1 Diabetes
– Children
– Drugs – steroids; antipsychotics

• Pregnancy
– Glucose levels can rise rapidly
– HbA1c is lower

• Conditions where red cell survival may be reduced
– Haemoglobinopathy
– Haemolytic anaemia
– Severe blood loss
– Splenomegaly
– Antiretroviral drugs

• Increased red cell survival
– Splenectomy

• Renal dialysis
– Reduced HbA1c, especially if treated with erythropoietin

• Iron and vitamin B12 deficiency
– Small effects on HbA1c

28

what is the glucose tolerance test

• Used to assess state of glucose tolerance
• 75g oral glucose load
• No restriction or modification of carbohydrate intake for preceding three days
• Fast overnight
• Test is performed in morning – seated; no smoking
• Blood samples for plasma glucose taken at 0hrs and 2 hrs

29

describe impaired glucose tolerance

Fasting plasma glucose: <7.0 mmol/l
2 hours after 75g oral glucose load: 7.8-11.0 mmol/l
• Affects 20% of population aged 40-65 years (UK)
• Increased mortality from cardiovascular disease (doubled)
• Natural history - 15% develop diabetes in 5 years, 15% return to normal
• Check fasting plasma glucose annually

30

what is impaired fasting glucose

(Fasting Hyperglycaemia)
Fasting plasma glucose: 6.0 – 6.9 mmol/l
• Intermediate state between normal glucose metabolism and diabetes
• Impaired glucose tolerance often present also (but not always)
• Found in 5% of population and prevalence increases with age
• Increased risk of vascular complications