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Phase 2a Medicine > endocrine conditions > Flashcards

endocrine conditions Flashcards

1
Q

Define Diabetes Mellitus

A

Syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance or both.

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2
Q

what are normal levels of blood glucose?

A

should be 3.5-8 mmol/L under all conditions.

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3
Q

how much glucose is produced everyday?

A

approx. 200g produced and utilised each day.
more than 90% from liver glycogen and hepatic gluconeogenesis and the remainder from renal gluconeogenesis.

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4
Q

where is glucose utilised?

A
  1. brain - MAJOR consumer - function depends on uninterrupted supply of it.
  2. tissues eg muscle and fat have insulin-responsive glucose transporters and absorb glucose in response to postprandial (post-meal) peaks in glucose and insulin.
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5
Q

how is glucose utilised in muscle?

A

stored as glycogen or metabolised to lactate or co2 and h20

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6
Q

how is glucose utilised in adipose tissue?

A
  1. fat uses glucose as a substrate to triglyceride synthesis.
  2. lipolysis of triglyceride releases fatty acids + glycerol - the glycerol is then used as a substrate for hepatic gluconeogenesis
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7
Q

what is meant by the biphasic insulin release?

A

b- cells sense rising glucose levels and aim to metabolise it by releasing insulin - GLUCOSE IS THE MAIN CONTROLLING FACTOR FOR INSULIN RELEASE
1st phase response: rapid release of stored insulin
2nd: if glucose levels remain high then 2nd phase is initiated. takes longer than 1st phase because more insulin must be synthesised.

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8
Q

name some other counter-regulatory hormones involved in diabetes

A

Adrenaline, cortisol, growth hormone
increase glucose production in the liver and reduce its utilisation in fat and muscle.

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9
Q

what are the main roles of insulin in a fed and fasting state?

A

fed state: main action to regulate glucose release by the liver
post-prandial state: main action to promote glucose uptake by fat and muscle

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10
Q

what conditions might diabetes be secondary to ?

A

pancreatic pathology: total pancreatectomy, chronic pancreatitis, haemochromatosis

endocrine disease: acromegaly and Cushing’s disease

drug induced: thiazide diuretics and corticosteroids

maturity onset diabetes of youth (MODY) : autosomal dominant form of type 2 diabetes - single gene defect altering beta cell function. tends to present <25yrs with a positive family history.

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11
Q

types of primary diabetes

A

type 1 - young, insulin deficiency with no resistance and immunogenic markers. - most prevalent in northern Europe. - finland.
type 2 - affluent lifestyle increasing in adolescents

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12
Q

What types of complication are associated with diabetes?

A

Hyperglycaemia causes serious microvascular and macrovascular problems.

Microvascular: retinopathy, nephropathy, neuropathy

Macrovascular: strokes, renovascular disease, limb ischaemia, heart disease

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13
Q

What is the main organ involved in glucose homeostasis and what is its role?

A

LIVER
1. stores and absorbs glucose as glycogen - in post-absorptive state.
2. performs gluconeogenesis from fat, protein and glycogen
3. if blood glucose is HIGH then the liver will make glycogen (convert glucose to glycogen) - GLYCOGENESIS - in long term liver will make triglycerides (LIPOGENESIS)

If blood glucose is low - liver splits glycogen (convert glycogen to glucose) - GLYCOGENOLYSIS - in long term liver will make glucose (GLUCONEOGENESIS) from amino acids/lactate

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14
Q

why is the brain so reliant on just glucose, and no other energy forms?

A

brain cant use free fatty acids to be converted to ketones that are converted to acetyl-CoA and used in Krebs cycle for energy production.

FREE FATTY ACIDS CANT CROSS BLOOD BRAIN BARRIER.

Glucose uptake by the brain is obligatory and isn’t dependent on insulin , and the glucose used is oxidised to co2 and h20.

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15
Q

what are some of the roles of insulin?

A
  1. supresses hepatic glucose output - decreases glycogenolysis and gluconeogenesis
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15
Q

what are some of the roles of insulin?

A
  1. supresses hepatic glucose output - decreases glycogenolysis and gluconeogenesis.
  2. increases glucose uptake into insulin sensitive tissues:
  3. muscle- glycogen and protein synthesis
  4. fat- fatty acid synthesis
  5. suppresses - lipolysis and breakdown of muscles (decreased ketogenesis)
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16
Q

difference between glycogenolysis and gluconeogenesis

A

Glycogenolysis :

Gluconeogenesis:

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17
Q

what are some roles of glucagon?

A
  1. increases hepatic glucose output
  2. reduces peripheral glucose uptake
  3. stimulates peripheral release of gluconeogenic precursors
  4. stimulates muscle glycogenolysis and breakdown (increased ketogenesis) , Lipolysis

peripheral( muscle and adipose tissue)

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18
Q

How is insulin formed?

A
  1. insulin is coded for on chromosome 11 produced in beta cells of islets of Langerhans on pancreas.
  2. Proinsulin is precursor of insulin.
  3. contains alpha and beta chains of insulin joined together by a C PEPTIDE.
  4. when insulin is being produced, the proinsulin is cleaved from its C peptide and is then used to make insulin which is then packaged into insulin secretory granules.
  5. thus when there is insulin release there will also be a high level of c peptide in the blood from the cleavage of the proinsulin from it..
  6. synthetic insulin doesn’t have c peptide - c peptide in blood tells you whether release is natural.
  7. after secretion, insulin enters the portal circulation and is carried to the liver, its prime target organ.
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19
Q

how many types of glut are there?

A

4

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20
Q

what is the function of glut1?

A

enables basal non insulin-stimulated glucose uptake into many cells

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21
Q

what is the function of glut2?

A

found in beta cells of the pancreas. transports glucose into the beta cell enables these cells to sense glucose levels.
it is a low affinity transporter transporter, that is it only allows glucose in when there is a high conoc of glucose ie when glucose levels are ghih and thus want insulin release.

via glut2, beta cells are able to detect high glucose levels and thus release insulin in response. also found in the renal tubules and hepatocytes

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22
Q

what is the function of glut3?

A

enables non - insulin-mediated glucose uptake into brain, neurones and placenta.

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23
Q

what is the function of glut4?

A

mediates much of the peripheral action of insulin.
its the channel through which glucose is taken up into muscle and adipose tissue cells following stimulation of the insulin receptor by insulin binding to it.

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23
Q

what is the role of the insulin receptor in glucose transport?

A

this is a glycoprotein coded for on the short arm of chromosome 19 which straddles the cell membranes of many cells.

when insulin binds to receptor it results in activation of tyrosine kinase and initiation of a cascade response - one consequence of which is migration of the glut-4 transporter to the cell surface and increased transport of glucose into the cell.

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24
Q

Define T1DM

A

metabolic disorder characterised by hyperglycaemia due to ABSOLUTE DEFICIENCY OF INSULIN.
Caused by autoimmune destruction of beta cells of pancreas.

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25
Q

give some epidemiology of t1dm

A
  1. manifests in childhood, peak incidence around puberty - can happen at any age
  2. usually younger <30 yrs
  3. lean
  4. northern europe - Finland
  5. incidence increasing esp children
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26
Q

give the aetiology of t1dm

A
  1. autoimmune - autoantibodies forming against insulin and islet beta cells - INSULITIS
  2. idiopathic - uncommon form that is characterised by absence of antibodies
  3. genetic susceptibility - hla-dr3-dq2 and hla-dr4-dq8
  4. association found with enterovirus
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27
Q

Give some Risk factors for t1dm

A
  1. northern europe
  2. fhx - hla-dr3-dq2 and hladr4dq8 >90%
  3. associated with other autoimmune disease:
  4. autoimmune thyroid
  5. coeliac disease
  6. addisons disease (Excess cortisol)
  7. pernicious anaemia

environmental: dietary constituents, enteroviruses eg coxsackie b4. vitd deficiency , cleaner environment may increase t1 susceptibility

28
Q

give the key presentation for t1dm

A

pt generally leaner than pt with t2dm

29
Q

Give the signs of t1dm

A

bmi <25kg/m2
glycosuria
ketonuria
failure to thrive in children: dropping off height and weight centiles
glove and stocking sensory loss
reduced visual acuity
diabetic retinopathy
diabetic foot disease:
1. reduced peripheral pulses
2. calluses
3. ulceration
4. charcot joint

30
Q

Give the symptoms of t1dm

A

polydypsia
polyuria
nocturia
weight loss
lethargy
recurrent infections eg pt complaining of balanitis or pruritis vulvae due to repeat candida infections
evidence of complications: blurred vision or parasthesia

31
Q

1st line investigation for t1dm

A

primary investigations:
1. random bg - taken at any time of day and >11mmol/L is diagnostic
2. fasting bg - >7.0 mmol/L
for both tests 1 abnormal vallue is DIAGNOSTIC in symptomatic individuals
2 abnormal values are required in asymptomatic individuals

for borderline case:
1. oral glucose tolerance test - >11mmol/L 2 hours after a 75g oral glucose load. 7.8 - 11 mmol/L suggests pre-diabetes
2. hba1c - measures amount of glycated haemoglobin >48mmol/mol suggests hyperglycaemia over the preceding 3 months.

32
Q

name some other investigations you could consider to t1dm

A
  1. c-peptide - NICE adise only measure in atypical presentations eg age >50 or bmi >25
  2. autoantibodies - if atypical features present and if positive,, suggests autoimmune beta-cell destruction. autoantibodies against the following might be found: glutamic-acid decarboxylase (gad) , insulin, islet cell, islet antigens, zinc transporter (ZnT8)
  3. vbg - if concerned about DKA - eg systemically unwell or vomiting - metabolic acidosis.
33
Q

Explain the pathophysiology of t1dm

A

results from autoimmune destruction by autoantibodies of the pancreatic insulin-secreting beta cells in islet of Langerhans.

causes insulin deficiency =continued breakdown of liver glycogen (producing glucose and ketones) = glucosuria and ketonuria as more glucose is in the blood.

in skeletal muscle and fats theres impaired glucose clearance:

bg is increased- when it reaches 10 mmol/L body cant absorb any more glucose- you get thirsty and get polyuria

pt. must have insulin because they’ll get get dka

34
Q

Name the 3 types of insulin and how they work?

A

short acting soluble - start working within 30-60 mins and last for 4-6 hrs. given 15-30 mins before meals in pts on multiple dose regimens and by continuous iv infusion in labour, during medical emergencies, at the time of surgery and in patents using insulin pumps
short acting insulin analogues - human insulin analogues (insulin aspart, lispro, glulisine) have a faster onset and shorter duration than the soluble insulin but overall don’t improve diabetic control. have reduced carry over effect compared to soluble insulin and are used with the evening meal in pts who are prone to nocturnal hypoglycaemia.
longer acting insulin - insulin premixed with retarding agents (Either protamine or zinc) precipitate crystals
can be intermediate (12-24 hrs) or long acting (more than 24hrs)

35
Q

why must t1dm pt have insulin?

A

DKA
due to reduced glucose supply to cells due to lack of insulin - drives formation of ketone bodies for energy form.

ketone bodies are strong acids and lower ph of blood.

eventual complete beta cell destruction results in the absence of serum c-peptide.

present very late often with only 10% of beta cells remaining.

36
Q

effect of ph lowered in blood?

A

impairs hb ability to bind to o2, acute kidney injury

37
Q

what is the diagnostic criteria for t1dm?

A

random glucose >11.1 mmol/L and 1 of the following:

  1. ketosis
  2. rapid wt loss
  3. age of onset<50 yrs
    bmi <25 kg/m”
  4. personal and/or family history of autoimmune disease
38
Q

Name the 4 differentials of t1dm

A

t2dm - c peptide present, autoantibodies present. older age, slow onset, obesity, stronger family hx, absence of ketoacidosis, initial response to anti-hyperglycaemic drugs.

neonatal diabetes: under 6 months. genetic testing with majority of mutations in the genes encoding the adenosine triphosphate-sensitive potassium channel and the insulin gene.

monogenic diabetes: MODY - nonobesse,young pt, with fhx of diabetes in 2 or more fhx. - c peptide present autoantibodies present.

LADA - latent autoimmune diabetes in adults - over 30 , non obese, respond initially to lifestyle mods and oral agents. production of insulin gradually decreases ( between 6 months and 5 years), such that treatment iwth insulin is required.
low to normal initial c-peptide level.
can be positive for at least 1/4 antibodies found in t1dm pts.

39
Q

what is the 1st line management for t1dm?

A

multidisciplinary approach

lifestyle:
1. educate pt on disease and risk
2. maintain lean weight, stop smoking and take care of feet (reduce gangrene risk)
3. pts should be educated regarding carbohydrate counting. - to match insulin dose.

INSULIN - THERAPY:

BASAL - BOLUS - 1ST LINE REGIMEN - basal long acting give regularly and supplement with bolus rapid acting before each meal.
BASAL: LEVEMIR (DETERMIR) twice daily. lantus (glargine) once daily is an alternative.

BOLUS: Humalog (lispro) or Novorapid (Aspart)

40
Q

Name other options for t1dm treatment other than 1st line

A
  1. mixed insulin regimen: mixture of short or rapid-acting and intermediate- acting insulin. give twice daily and used in those who cant tolerate multiple injections as part of a basal-bolus regimen
  2. continuous insulin infusion: if pt. has disabling hypoglycaemia or persistently hyperglycaemic (HBA1C>69 mmol/mol) on multiple injection insulin therapy.
41
Q

Name 4 complications of insulin therapy

A
  1. hypoglycaemia - most common (also caused by sulfonylurea - antidiabetic drug)
  2. injection site - lipohypertrophy
  3. insulin resistance - mild and associated with obesity.
  4. weight gain - insulin makes people feel hungry.
42
Q

which antidiabetic medication causes hypoglycaemia as a S.E

A

Sulfonylurea

43
Q

How to monitor for t1dm?

A

Hba1c: 3-6 mths - target <48mmol/L

self-monitoring: 4 times a day - before meals and bed. targets:
on waking- 5-7 mmol/L
other times of the day including before meals: 4-7 mmol/L
bedtime: personalised depending on last meal.

annual diabetic review.

44
Q

Define DKA

A

acute metabolic complication of t1dm. characterised by absolute insulin deficiency - most common acute hyperglycaemic complication of t1dm.

45
Q

give some epidemiology of dka

A

4% of t1dm pts get dka each year. 20,000 cases per yr. dka more common in under 10 and non white rather than white.

46
Q

name the risk factors for dka

A
  1. infection
  2. undiagnosed diabetes
  3. inadequate insulin or non-adherence to insulin therapy
  4. myocardial infarction
  5. physiological stress eg: trauma or surgery
  6. other co-morbidities eg: hypothyroidism and pancreatitis
  7. drugs that affect carbohydrate metabolism: eg: corticosteroids, diuretics and salbutamol
47
Q

Signs of DKA

A
  1. fruity smell of acetone on breath
  2. dehydration :
    mild - only just detectable
    moderate - dry skin and mucus membranes : reduced skin turgor
    shock: tachycardia, hypotension ( late), drowsiness, reduced urine output
  3. Kussmaul respiration: deep, laboured breathing trying to reverse the metabolic acidosis
  4. hypotension
  5. abdominal tenderness
  6. reduced consciousness/coma
48
Q

Symptoms of DKA

A
  1. Abdominal pain
  2. leg cramps
  3. headache
  4. nausea and vomiting
  5. polyuria
  6. polydipsia
  7. weight loss
  8. inability to tolerate oral fluids
  9. lethargy
  10. confusion
49
Q

what does the annual diabetic review consist of?

A

assessment of injection site problems, retinopathy, nephropathy, diabetic foot problems (neuropathic problems), cardiovascular risk factors and thyroid disease.

Retinopathy: annual screening
Nephropathy: renal function (eGFR) and albumin: creatinine ratio (ACR)
Diabetic Foot problems: full exam, footwear, monofilament assessment of neuropathy, vascular assessment +/- dopplers.
CV risk factors: primary/secondary prevention strategy with optimisation of bp, lipids, weight, smoking and others
Thyroid Disease: screening blood test

50
Q

Name the macrovascular complications of t1 diabetes

A

cardiovascular: ischaemic heart disease, heart failure, peripheral vascular disease
cerebrovascular: stroke

51
Q

Name the microvascular complications of t1 diabetes

A

neuropathy:
1. mononeuropathy
2. polyneuropathy: glove and stocking
3. Amyotrophy : painful proximal lower limb muscle wasting
4. Autonomic neuropathy : gastroparesis, erectile dysfunction, postural hypotension

Renal:
diabetic nephropathy and CKD

Retinopathy:
1. non-proliferative and proliferative
2. maculopathy

52
Q

Name the general complications of t1dm

A
  1. dka
  2. hypoglycaemia: complication of insulin treatment, especially insulin doses without a meal.
  3. diabetic kidney disease - involves glomerular mesengial slerosis leading to proteinuria and progressive decline in glomerular filtration.
  4. retinopathy
  5. peripheral or autonomic neuropathy
  6. cardiovascular disease: increased risk of atherosclerosis, hyaline arteriolosclerosis.
53
Q

Define t2dm

A

characterised by insulin resistance and less severe insulin deficiency.

54
Q

Give some epidemiology for t2dm

A

affluent lifestyle
older - usually over 30 but now more prevalent in teens
south asian african carribean
middle eastern and hispanic
m>F

55
Q

Give the aetiology of t2dm

A
  • decreased insulin secretion +/- increased insulin resistance.
  • associated with obesity, lack of exercise, calorie and alcohol excess
  • no immune disturbance
  • no HLA disturbance but there is a stronger genetic link
  • polygenic disorder
56
Q

Name the risk factors of t2dm

A
  • fhx - genetics - 75% risk if both parents have t2dm.
  • increasing age
  • obesity and poor exercise - can trigger t2dm in genetically susceptible
  • ethnicity - middle eastern, south-east asian and western pacific
  • obesity
  • HTN
  • Dyslipidemia - especially with low high-density lipoprotein (HDL) and/or high triglycerides
  • Gestational diabetes
  • polycystic ovary syndrome
  • drugs: corticosteroids, thiazide diuretics
57
Q

t2dm key presentation

A

pt generally overweight

58
Q

signs of t2dm

A
  • glove and stocking sensory loss
  • reduced visual acuity
  • diabetic retinopathy
  • diabetic foot disease (reduced peripheral pulses, calluses, ulceration, charcot joint)
  • acanthosis nigricans - black pigmentation at the nape of the neck and in the axillae
59
Q

symptoms of t2dm

A
  • wt loss
  • polyuria
  • polydypsia
  • lethargy
  • recurrent infections
  • evidence of complications eg : blurred vision or paraesthesia
60
Q

investigations for t2dm (other than 1st line)

A
  • fasting lipids: pts with diabetes often have dyslipidaemia
  • u+e’s : reduced eGFR due to diabetic nephropathy
  • urine albumin: creatinine ratio: diabetic nephropathy leads to protein leaking through the glomerular basement membrane.
61
Q

Explain the diagnostic criteria for t2dm

A

-ELEVATED PLASMA GLUCOSE SAMPLE AND/OR HAB1C ON 1 OCCASION IF SYMPTOMATIC OR 2 IF ASYMPTOMATIC.

pre-diabetic phase - impared fasting glucose and impared glucose tolerance. - show increased risk of dm

patients with ifg: raised fasting glucose and normal ogtt
patients with igt: raised ogtt, may or may not have a raised fasting glucose.

62
Q

name the differentials for t2dm

A
  • pre-diabetes
  • t1dm
  • lada
  • monogenic diabetes
  • ketosis - prone diabetes - idiopathic diabetes. unprovoked ketosis or ketoacidosis. some pts may have type 2 presentation.
  • gestational diabetes
63
Q

1st line management for t2dm

A

lifestyle: target 48mmol/mol (6.5%). Metformin commenced if hba1c rises above.
1. high fibre, low glycaemic index source of carbs
2. low fat dairy products and oily fish.
control intake of trans and saturated fats, and limit sucrose- containing foods.
3. discourage the use of foods marketed specifically for people with diabetes
4. aim for an initial weight loss of 5-10%

64
Q

Define Hypercalcemia

A

higher than normal calcium levels in the blood - over 10.5 mg/dL

65
Q

what are the clinical manifestations of hypercalcaemia

A

abdo pain
vomiting
constipation
dehydration
polydipsia
polyuria
absent reflexes
muscle weakness
weight loss
depression
confusion
hallucinations
stupor
hypertension
pyrexia

66
Q

Explain the pathophysiology of DKA

A
  • Complication of t1dm.
    TRIAD OF HYPERGLYCAEMIA, ACIDOSIS AND KETONAEMIA = dehydration and electrolyte imbalances.

lack of insulin - body unable to utilise glucose - accumulation of glucose = hyperglycaemia. increase in hepatic glucose production through glycogen breakdown (glycogenolysis) and increased formation of glucose from other substrates (gluconeogenesis).

increase in counter-regulatory hormone release (cortisol, glucagon, growth hormone) exacerbates the hyperglycaemia and drives the production from alternative energy source.

lack of glucose utilisation = lipolysis (fat breakdown) = increased serum free fatty acids. fatty acids used as an alternative energy source through ketogenesis.

this increases no. of ketone bodies (acetone, beta- hydroxybutyrate and acetoacetate) within the blood leading to ketonemia. ketone bodies are weak acids = significant acidosis and severe illness in increasing quantities.

as DKA progresses, raised plasma glucose leads to osmotic diuresis and profound hypovolemia, exacerbated by vomiting. Leads to major electrolyte derangements, reduced consciousness and eventual death if not managed urgent.

67
Q

what is the main ketone body within DKA?

A

3-BETA-HYDROXYBUTYRATE

68
Q

Investigations for 1st line DKA

A

1st line: primary investigations:
Lab glucose : >11.0 mmol/L
venous/arterial blood gas: quickest way to get ph and hco levels. abg in inital blood gas sample for diagnosis, later samples venous if possible - ph < 7.3 or bicarbonate <15 mmol/L

Ketone testing: capillary blood ketone 3mmol/L or more or urinary ketones 3 or above

69
Q

Name some other tests to confirm DKA

A
  • Urine Dip : glycosuria and ketonuria
  • U + E : electrolyte derangement and acute kidney injury due to dehydration
  • FBC AND CRP : raised inflammatory markers may suggest underlying infection as a precipitant
  • LFTs :
  • Troponin
  • Infection screen : if an infection is the suspected trigger
  • ECG
  • Imaging : Chest x-ray

Phase 2a Medicine (22 decks)

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