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test > Case 17 > Flashcards

Case 17 Flashcards

1
Q

What is the MOA of metformin?

A

Activates AMP dependent protein kinase (hepatically) to reduce gluconeogensis and potentiates effects of endogenously secreted insulin

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2
Q

Why is Metformin first line option?

A

^Insulin dependent glucose uptake into tissues. Inhibits GI absorption of carbs. Limited ADRs

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3
Q

When is Metformin contraindicated ?

A

Chronic kidney disease. May provoke lactic acidosis

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4
Q

What is the second line drug for T2D after metformin ?

A

Gliclazide. Enhances insuline secretion in pancreas

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5
Q

What does Gliclazide act on ?

A

B cell K ATP effluxes channel to block K efflux. Depolarises B cell –> Ca influx and IP3 mediated enhanced secretion of insulin

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6
Q

Px starts on T2D medication and starts experiencing jaundice, what medication are they on ?

A

Gliclazide, shows severe hepatic impairment. Normally prior to medication

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7
Q

What is the name of the drug that inhibits breakdown of incretins to 2ndarily enhance insulin secretion from pancreas?

A

Saxagliptin, often used with metformin or Gliclazide to ^sensitivity to insulin

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8
Q

What is the action of DDP-IV?

A

Dipeptidyl peptidase IV normally breaks down incretins (GLP-1).

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9
Q

What is Exenatide and how is it administered ?

A

SC injection. mimics incretin to ^insulin secretion from the pancreas.

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10
Q

How does Exenatide work ?

A

activates GLP-1 receptors to cause ^insulin secretion. ^insulin sensitivity when used with metformin and Gliclazide

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11
Q

What is Gliflozin ?

A

SGLT2 inhibitor, ^insulin dependent peripheral glucose uptake and inhibits digestion/absorption of carbs.

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12
Q

What are the superficial causes of T2D ?

A

Polygenic and environmental risk fx acting together (obesity, lack of exercise, poor diet)

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13
Q

What ethnic groups are more at risk of T2D?

A

6x more common in south asian

3x if afro-caribbean and African descent

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14
Q

What is the lifelong risk of T2D if one or both parents have the condition ?

A 
One = 40% risk 
Both = 70% risk
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15
Q

What is the thrifty phenotype ?

A

Low activity tendencies that store energy, didn’t die in past famines so genes passed on

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16
Q

What is heritability ?

A

Proportion of observed differences between members of population that are due to genetic influence.
Variance in genotype / variance in phenotype

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17
Q

What is the difference between monozygotic and dizygotic twins ?

A

MZ share genome

DZ share half

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18
Q

What are the cons to twin studies ?

A

susceptible to bias (concordant twins ^likely to join) , age at recruitment (may develop at different times) , assumes twins share environmental fx.

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19
Q

What is MODY ? which gene is its most common cause ?

A

maturity onset diabetes of the young. <25 y/o. no obesity, ketosis, B cell autoimmunity.
HNF1A.

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20
Q

What are neonatal diabetes and mitochondrial diabetes examples of ?

A

Monogenic diabetes

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21
Q

What is the action of GCK ?

A

catalyses phosphorylation of glucose and controls rate limiting step of glycolytic pathway

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22
Q

What do mutations of the 7p chromosome cause ?

A

mild, stable fasting hyperglycaemia (mutated GCK) without complication so no tx required. Px needs to control diet and exercise

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23
Q

What is permanent neonatal diabetes ?

A

IUGR, sx hyper (<6 months) , ketoacidosis. pancreas insensitive to BG stops producing insulin.

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24
Q

What is the tx for permanent neonatal diabetes ?

A

Insulin therapy correct hyperglycaemia and results in growth catch up.

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25
Q

What is the non syndromic form of permanent neonatal diabetes ?

A

mutation in the insulin so still produced but not recognised by receptors.

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26
Q

What is the function of the KCNJ11 and ABCC8 genes ? what happens when they don’t function

A

Make up the K channel on beta cells allowing binding. If no binding then can’t depolarise so no insulin release.

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27
Q

What is the difference with the syndromic form of neonatal diabetes ?

A

Shows other associated features.

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28
Q

What is the pathway from the abdominal aorta to the external iliac arteries ?

A

Abdo –> L/R common iliac arteries -> internal/external iliac.

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29
Q

What is the significance of the inguinal ligament for the femoral artery ?

A

Below the inguinal ligament = fem artery

Above = external iliac artery.

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30
Q

What is the path of the deep femoral ?

A

From inguinal ligament beneath satorius muscle gives off deep femoral (thigh) and superficial femoral (below thigh). Deep then branches into medial/lateral circumflex

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31
Q

What structures branch from internal iliac ?

A

Sup/inf gluteal pass back through greater sciatic foramen (one above and below piriformis muscle).

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32
Q

What is the pathway of the great saphenous vein ?

A

ankle up medial side to thigh passes through opening in fascia lata (saphenous hiatus) then joins femoral vein.

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33
Q

Describe the path of blood flow after from the femoral vein after the inguinal ligament …

A

External iliac, joins to internal iliac -> common iliac. R/L common iliac then join at midline –> IVC.

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34
Q

Where do the obturator and femoral nerves arise from ?

A

anterior rami of 2nd to 5th lumbar nerves and 1st, 2nd, 3rd sacral nerves

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35
Q

What muscles are supplied by the femoral nerve ? (7)

A

iliac, 4 heads of quads, pectinous, sartorius

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36
Q

What is the path of the obturator nerve ?

A

emerges below medial border of psoas major. passes through obturator canal just above obturator internus. Emerges over top of obturator externus. Branches run between adductor muscles.

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37
Q

What muscles does the obturator nerve supply ?

A

Obturator externus, adductor braves and longus, ant part of adductor Magnus

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38
Q

What are the 4 quadricep muscles , where is their origin, what is their function ?

A

Extend the knee
Vastus intermedius, medialis and lateralis arise from femur
rectus femoris arises from hip bone

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39
Q

what are the hamstring muscles and what is their function ?

A

knee flexion, hip extension

Semimembranosus, semitendonosus, biceps femoris

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40
Q

What is adductor canal ?

what is it covered by ?

A

Space between adductor longs and vistas medialis. Femoral vessels run through it from front to back of thigh. Adductor canal is covered by satorius muscle

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41
Q

How are the functions of the hamstrings changed ?

A

Flexion of knee resisted by quads -> hamstring extends hip.

Extension of hip resisted by hip flexors -> hamstring flexes knee.

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42
Q

What two muscles help the hamstrings to produce flexion? where do they insert ?

A

Sartorius and gracilis. Insert close to the semitendinosus (medial side of the knee)

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43
Q

What are the muscles in the posterior compartment of the leg ?

A

Popliteus (medial rotate tibia)
Plantaris (plantarflexion)
Gastrocnemius

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44
Q

What forms the calcaneal tendon ?

A

‘Achilles’ tendon’. Gastrocneumius joins soleus muscles.

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45
Q

What do the femoral artery and vein become after running beneath the sartorius muscle ?

A

Emerge at back behind adductor Magnus as popliteal artery and vein.

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46
Q

What are the branches of the popliteal artery ?

A

Above the knee; two sup genicular arteries (lat/med)
At the knee; two branches to gastrocnemius
Below the knee; two inf genicular arteries (med/lat)

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47
Q

Where does the sciatic nerve divide and what does it divide into ?

A

Above the knee divides into the tibial and common perineal nerve

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48
Q

What is the path of the tibial nerve, what does it supply ?

A

Runs down the midline, passes between two heads of gastrocnemius. Supplies popliteus, gastrocnemius and plantaris (post leg)

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49
Q

What muscles perform dorsi and plantar flexion ?

A

Dorsiflexion, tibialis ant

Plantar, lifts whole body so large muscles ; gastrocnemius, solaris, plantaris

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50
Q

What is the insertion of the Achilles tendon ?

A

Broad area at the back of the Calcaneus

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51
Q

What are the features of neonatal diabetes ?

A

IUGR, hyperglycaemia (<1 month) , lack of insulin (resolves after 18 months). Intermittent hypers during intercurrent illness.

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52
Q

What is the structure of K ATP channel ?

A

made of 4 subunits - Kir6.2

Forms channel pore surrounded by 4 sulfonylurea receptors that reg activity

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53
Q

How do sulfonylureas work ?

A

Bind to SUR1 receptor (same action as ATP) which closes the channel. K inside the cell^ -> depolarisation which allows insulin to be released.

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54
Q

What is Donohue syndrome ?

A

Insulin receptor syndrome. ^insulin release from receptor mutations, pre/post natal growth failure.

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55
Q

What distinguishes T2D from MODY ? (4)

A

polygenic, gene-gene and gene-environment interaction, later onset, pedigree rarely multigenerational

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56
Q

What are the problems with a genetic association study ?

A

Control and case need to be well matched, multiple testing (eventually scientists found a P value they like) , publication bias

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57
Q

What is epigenetics ?

A

stable heritable modification of chromosomes without altering DNA sequence through methylation or histone modification -> alters transcriptional potential of genes (silencing)

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58
Q

What was the Barker hypothesis ?

A

decreased birth and 1 yo weight -> ^risk of IHD.

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59
Q

Poor gestational nutrition leads to what features in later life ? (5)

A

^CHD, atherogenic lipid profile, poor blood coagulation, ^stress response, ^obesity

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60
Q

What is the difference between rate and ethnicity ?

A 
Race = biological makeup eg. skin colour variation 
Ethnicity = culture that you associate with
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61
Q

What are the problems with putting people into limited standard categories ?

A

Groups stable new ones cant emerge, favours dominant groups over diversity.

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62
Q

What are the aims of the ‘together for health diabetes’ delivery plan

A

Prevention (educate on healthy lifestyle) detection (encourage GPs) Mx (encourage self mx)

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63
Q

What 3 fx influence the age structure of population ?

A

Fertility, mortality, migration

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64
Q

What is Fries’ compression of morbidity theory ?

A

Lifespan fixed, chronic disease can be postponed

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65
Q

What are the 4 ‘geriatric giants’ ?

A

impairment, incontinence, Iatrogenic, instability

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66
Q

Why is the target BP for elderly 140/80 but no lower ?

A

Increases the risk of postural hypotension

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67
Q

What are the factors of the phenotype model of frailty ?

A

3/5 required; unintentional weight loss, decreased walking speed, decreased grip strength, subjective exhaustion, decreased physical activity

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68
Q

What indicator of Sarcopenia would be seen on CT ?

A

Shrinking psoas muscle

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69
Q

What is the contents of the femoral triangle and what structure is the only one palpable ?

A

Femoral nerve artery and vein. Femoral artery is the only palpable one.

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70
Q

How is the femoral triangle split into fascial compartments ?

A

Femoral artery and vein then

Femoral nerve and iliopsoas in a different one.

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71
Q

Where would you place the needle for a venous sample in relation to the femoral artery ?

A

Medially (space)

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72
Q

What are the contents of the femoral canal from lateral to medial ?

A

femoral nerve , femoral artery , femoral vein, empty space, lymphatics

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73
Q

What is the superior end of the femoral canal bounded by? Why is this structure significant ?

A

Bounded by femoral ring (just underneath inguinal ligament). Common site of hernias

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74
Q

What is the difference between femoral and indirect inguinal hernias ?

A

Femoral hernias; below inguinal ligament, medial to femoral artery
Indirect hernias; lateral to the inf epigastric vessels

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75
Q

What is Meralgia Paresthetica?

A

Lat cutaneous nerve of the thigh passes through inguinal ligament - trapped/compression
Leads to tingling, numbness, burning in lateral thigh

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76
Q

What are the risk fx for Meralgia Paresthetica ?

A

Tight clothing, obesity, weight gain, pregnancy, diabetic nerve injury

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77
Q

What nerve supplies the posterior lower leg laterally? Common loss of sensation in diabetic neuropathy…

A

Sural nerve, ‘pins and needles in right lower limb’

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78
Q

What is the blood supply and nerve innervation of the anterior compartment of lower limb ?

A

Blood supply - anterior tibial artery

Nerve - deep femoral

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79
Q

What compartment of the lower limb is supplied by the fibular artery and innervated by the superior fibular nerve ?

A

Lateral compartment

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80
Q

How would you differentiate between the lateral and posterior deep sides of lower limb in a cross section ?

A

Lateral is the fibia side (small bone)

Posterior deep/medial is the tibia (large bone)

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81
Q

What is the blood supply and innervation of the posterior deep and superficial compartments ?

A

Bloody supply - Posterior tibial artery and fibular artery

Innervation - Tibial nerve

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82
Q

When is a fasciotomy carried out? what is it ?

A

Bleeding into osteofascial compartment ^pressure as walls are resistant to distension (Ischaemia risk). Incision into leg to relieve pressure/sx.

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83
Q

What are the muscles of the lateral compartment of the leg ? what is their innervation and function ?

A

Fibularis longus and brevis. Eversion of the foot, innervated by the superficial fibular nerve

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84
Q

What are the risk fx for varicose veins ?

A

age (peak 50-60) , sex (female - hormone ^during pregnancy) , obesity, occupation, hereditary

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85
Q

What is the most common sight of varicose veins ?

A

Small saphenous vein (posterior knee)

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86
Q

What arteries can be damaged during proximal femur fractures ? What is their origin ?

A

Medial and lateral circumflex femoral arteries. Originate from the branches of profunda femoris.

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87
Q

What is plantar tendonitis ?

A

Persistant pain affecting origin of fascia and surrounding perifascial surfaces. Intense for first few steps of walking then lessens

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88
Q

What does dry gangrene occur ? What provides the supply to the area

A

Reduced blood supply to the distal regions. Dorsalies pedis (continuation of ant tibial artery)

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89
Q

What is the ABI ? what is the normal range of values ?

A

Ankle brachial pressure index, ratio of systolic BP in posterior tibial artery to brachial artery. Normal is 0.9 - 1.4

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90
Q

What do high and low ABIs indicate ?

A

High ABI = calcification/hardening of the vessel

Low ABI = arterial disease (the lower the more severe)

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91
Q

What condition arises from stretching or compression of the common fibular nerve ?

A

Foot drop, unable to dorsiflex the foot

92
Q

What are the 4 lower limb pulses required for exam and where are they located ?

A

Femoral (halfway between ASIS + pubic symphysis)
Popliteal (flex knee supine to relax popliteal fascia)
Post tibial artery (post to medial malleolus)
Dorsalis pedis (lateral to extensor hallucis longus tendon)

93
Q

How many tibial arteries and veins are normal ? What can be used to visualise blood flow?

A

One tibial artery corresponds to two tibial veins. Colour doppler shows pulsing artery.

94
Q

What is the normal range of plasma glucose if fasting and 2 hours post prandial ?

A

Fasting = 4-6 mmol/L

2 hours post prandial <7.8

95
Q

What are the endocrine secretions of the pancreas that help maintain BG levels ?

A

Insulin, glucagon, somatostatin, pancreatic peptide

96
Q

What are the exocrine secretions of the pancreas and what is their function ?

A

HCO3 and digestive enzymes into the duodenum. Digestion and regulate pH of contents leaving the stomach

97
Q

What transporter regulates glucose transport into B cells ?

A

GLUT2

98
Q

What happens when glucose moves into the B cells ?

A

Activates GCK which ^ATP inhibiting K efflux channels. This traps K in cells –> depolarisation –> Ca influx –> Insulin secretion through IP3 signalling.

99
Q

What is the insulin receptor and what happens when insulin binds to it ?

A

Transmembrane tyrosine kinase receptor that exists as a heterodimer.
Insulin binding causes autophosphorylation –> phosphorylation of IRS (insulin receptor substrates) that globally act to reduce BG.

100
Q

What effects does insulin have that can become disregulated during T2DM ? (5)

A

Glycogenolysis, gluconeogenesis decrease

Glycolysis, G uptake, glycogen synthesis ^

101
Q

What is glycation and what does it result in ?

A

uncontrolled carb reactions that oxidise biological macromolecules. Forms advanced end products (AGEs) that cause the O2 damage/imapired function.

102
Q

How is the rate of glycation effected by BG levels ?

A

^BG = ^chance of glycation reactions occurring

103
Q

What is glycosylation ?

A

enzymes control physical reactivity of carb molecules and regulate sugar modifications.

104
Q

How is BG measured currently and what are future methods being worked on ?

A

Finger prick through meters
Continuous glucose monitoring (interstitial fluid)
Non invasive is the goal

105
Q

What microvascular disease can arise from poor diabetes management and why ?

A

Small BVs loose structure and function

Retinopathy (leakage) , nephropathy , neuropathy (myelin damage)

106
Q

What are the risk fx for diabetes ? which is the most important ?

A

Obesity/weight gain is largest

Then; poor diet, lack of exercise / sedentary , stress , alcohol, smoking

107
Q

There are over 36 identified genes for T2DM. What is the function of the KCNJ11 gene ?

A

Encodes islet ATP sensitive K channel kir6.2

108
Q

What is the normal glucose regulation post prandially ?

A

^glucose -> ^GLP-1 (incretins) to trigger insulin release. Insulin ^ uptake into cells via GLUT-4.

109
Q

What regulates GLP-1 ?

A

DDP-IV (depiptidyl peptidase - IV)

110
Q

What is the 1st line drug for T2DM? When is it contraindicated ?

A

Metformin (Biguanide). Can ^lactic acid so contra for chronic kidney disease. Needs some level of endogenous insulin production from B cells.

111
Q

What is Metformin’s MOA ?

A

Decreases hepatic ATP -> activates AMP protein kinase to decrease gluconeogenic gene formation and stop glycerol 3-P-DH formation. This ^NADH , ^lactate and slows gluconeogenesis further -> BG falls.

112
Q

Name a sulfonylurea, when are they contraindicated ?

A

Gliclazide. In obesity because may cause weight gain

113
Q

How does Gliclazide work ?

A

Binds to sulfonylurea receptor on K ATP channel (blocks it) so ^depolarisation/Ca influx -> ^insulin secretion.

114
Q

What is the action of saxagliptin ?

A

Inhibits DDP-IV, ^GLP-1 half life so ^insulin and decreases glucagon.

115
Q

Why can you not completely inhibit the action of DDP-IV ?

A

Normall breaks down GLP-1 to stop too large a hypoglycaemic effect postprandial.

116
Q

What type of drug is Exanitide and what is its MOA?

A

Incretin mimetic. Actiates GLP-1 receptor to ^insulin secretion from B cells and decrease glucagon and gastric emptying

117
Q

Name a drug of the thiazolidinedione class and explain why it is not used 1st line ?

A

Pioglitazone. ^peripheral insulin sensitivity but not 1st line due to serious ADRs (cancer risk ^).

118
Q

What is the MOA of pioglitazone ?

A

Complexes with peroxisome proliferator activated receptor gamma (PPAR-gamma) as an adipocyte gene transcription regulator.

119
Q

What is the effect of the Pioglitazone complex ?

A

Adipocyte differentiation, lipogenesis, FA uptake and glucose uptake all increase

120
Q

What is Sitagliptin ?

A

Gliptin drug (same as saxagliptin) that inhibits DPP-IV thus inhibiting inactivation of GLP-1.

121
Q

A px with 10 yr hx of T2DM starts getting altered sensation in hands and feet. He has difficult discriminating between different coins. When walking the floor feels odd and he sometimes loses balance. What is the dx ?

A

Symmetrical sensory polyneuropathy

122
Q

A 72 man with T2DM experiences SOB and metabolic acidosis. What medication is likely to be the cause ?

A

Meformin. Causes lactic acidosis in chronic kidney disease

123
Q

A 57 man with hx of T2DM is hungry, confused, sweaty. What medication is likely to be causing this ?

A

Glibenclamide, associated with weight gain (sulfonylurea)

124
Q

Which drug used in mx of T2DM, directly inhibits K channels in the beta islet cells ?

A

Gliclazide, sulfonylurea MOA

125
Q

74 fem suspected T2DM. fasting BG 5.7 mmol/L and 2 hour OGTT of 8.4. Whats dx?

A

Impaired glucose tolerance because fasting is normal (4-6) but oral glucose tolerance test >7.8

126
Q

85 with dry feet, breaks (fissures) in the skin. O/E feet warm and palpate both pulses. Plantar aspect R foot has large callus. Hx of T2D with poor control, what’s the dx ?

A

Neuropathic foot ulcer

127
Q

What is Acarbose MOA?

A

Inhibits enzymes in SI that break down carbs –> glucose

128
Q

Px with HbA1c 9%, kidney function decline and proteinuria. What stage of diabetic nephropathy is she in?

A

Stage 4 due to proteinuria

129
Q

What does a measurement of 1.4 on the ABI indicate ?

A

Vessel calcification, inconclusive due to non compressible vessels.

130
Q

What part of the pancreas is intraperitoneal ?

A

Tail

131
Q

What is the risk of offspring developing DM if 1 and 2 parents have the disease ?

A

1 parent = 40%

Both parents = 70%

132
Q

When observing Ramadan what level should you BG not fall below ?

A

<4 mmol/L

133
Q

What GFR shows stage 2 nephropathy ?

A

60-89 mL/min

134
Q

What is the biggest risk fx for T2DM ?

A

Weight gain

135
Q

What are the components of metabolic syndrome ?

A

Central obesity, HT, ^triglycerides, low HDL, insulin resistance

136
Q

What are the stringent and flexible goals for glycemic control ?

A 
Stringent = 48-58 mmol/mol 
Flexible = 60-69 mmol/mol
137
Q

What are the differential diagnosis for neuropathic pain ? (6)

A

Vasculitis, alcohol misuse, B12/folate def, drugs (metformin can cause B12 def) , uraemia, hypothyroidism

138
Q

How would you manage neuropathy non pharmacologically ?

A

Improve glycaemic control, tx reversible causes. Foot care (daily inspection, check footwear, never walk barefoot)

139
Q

What drugs would you consider for neuropathic pain ?

A

Duloxetine (1st line) or Amitriptyline then add a weak opioid if not controlled

140
Q

What instructions would you give a diabetic patient who is about to go through Ramadan?

A

Monitor BG 2-4 times a day. If if drops below 4 mmol/mol then break the fast.

141
Q

What changes to medication would be needed for a px about to go through Ramadan ?

A

Change metformin to 1000mg twice daily.

Stop sulfonylureas and SGLT2s if possible, reduce to half if not.

142
Q

What are the reasons for confusion ? (7)

A

vascular dementia, dehydration, recent bereavement, depression (pseduodementia) , infection, hypo/hyperglycaemia, hypothyroidism

143
Q

What levels of GFR and creatinine would you stop giving Metformin to a px ?

A

Creatinine >150 umol/L and GFR 30-45

144
Q

56 yo female presents with hx of HF, polyuria, thirst and BMI 27.6. Her fasting glucose is 8.9. What is you tx plan ?

A

Nutritional advice and targeted weight loss. Fasting glucose is high but this is first presentation

145
Q

Why do ketone bodies ^ during starvation ?

A

Acetyl CoA can’t enter Krebs cycle because Oxaloacetate is used for gluconeogensis during fasting. So to prevent build up (would switch off TCA cycle) they’re converted to ketone bodies in the liver.

146
Q

Why isn’t DKA as common in T2DM?

A

The degree of insulin deficiency is smaller in the hyperosmolar hyperglycaemic state. Endogenous insulin enough to inhibit hepatic ketogenesis but insufficient to inhibit hepatic glucose production.

147
Q

What are the causes of MODY 2 and 3. Which is more common?

A

MODY 2 = GCK mutaiton
MODY 3 = HNF1A
MODY 3 is the most common (60%).

148
Q

What is the consequence of MODY 2 ?

A

GCK normally phosphorylates G-6-P, acts as sensor within pancreatic beta cells. So ^BG is required to stimulate insulin response in MODY 2.

149
Q

What is aspirins MOA ?

A

Irreversible cyclooxygenase inhibitor. Suppresses PGs and thromboxane synthesis which reduces platelet aggregation.

150
Q

When is aspirin indicated ?

A

CV disease 2ndry prevention. Acute stroke after 14 days. ACS.

151
Q

What is the serious contra of aspirin use ?

A

Under 16 yo –> Reye’s syndrome (swelling of liver and brain).

152
Q

What are the indications of Ramipiril?

A

Hypertension if under 55 and not of afro-carribbean origin, HF, nephropathy/kidney damage/failure.

153
Q

What are the ADRs of metformin ? (4)

A

GI disturbance, risk of lactic acidosis, ^if >65 yo, renal impairment.

154
Q

What is the MOA of simvastatin ?

A

Competes with HMG-CoA for HMG-CoA reductase to reduce amount of mevalonic acid (precursor of cholesterol)

155
Q

What is the mx for metabolic syndrome ?

A

Reduce kcal intake. Prolonged need for large amounts of fat to be lost (and then maintained)

156
Q

What is the formula for GFR and how can this be broken down further ?

A 
GFR = Kf x net filtration rate 
NFR = Glomerular hydrostatic P - Bowman's capsule P - Glomerular oncotic P
157
Q

What is required for the dx of diabetes ? List the fx (4)

A

Asx needs 2 fx , sx needs 1

Fx; fasting glucose >7 , random glucose >11 , OGTT >11, HbA1c >48 or 6.5%

158
Q

What is the Km of GLUT2 ?

A

High so low affinity. This means glucose only binds in the pancreas when in higher concentrations

159
Q

In terms of phosphorylation, what is the action of insulin ?

A

Insulin is a dephosphorylating hormone. Turns off phosphorylase and turns on synthase eg. glycogen synthesis

160
Q

What is the action of insulin on PFK and FBPase 2 ?

A

PFK - switches it on
FBPase 2 - switches it off
Leads to more glycolysis and less gluconeogenesis which leads to decreased BG

161
Q

What are the clinical features of hyperosmolar hyperglycaemic state ?

A

Dehydration, stupor/coma, impaired consciousness.

162
Q

What is the mx for HHS ?

A

freq monitor osmolality (2Na, G, urea)
px sensitive to insulin so BG may plummet. Infuse insulin 3u/h for 2-3h then 6u/h if BG falling too slowly. 0.9% saline (fluid replacement) and LMWH (prophylaxis).

163
Q

What are the risk fx for nephropathy ?

A

HT, poor glycaemic control, fam hx, diet

164
Q

What are the sx of nephropathy ? (6)

A

Early on asx then; GI disturbance (vomit, loss of appetite), weight gain (fluid retention)
Chronic –> HF , pulmonary oedema

165
Q

What is focal segmental sclerosis ?

A

Glomerular enlargement for compensation of loss of nephrons in other areas of the kidney

166
Q

Where are venous ulcers located and how would they look ?

A

Area between lower calf and medial malleolus. Shallow/flat margins, heavy exudate.

167
Q

How would you treat a venous ulcer ?

A

Compression therapy, leg elevation, surgical mx (rare)

168
Q

What conditions ^risk for arterial ulcers ?

A

Diabetes, HT, smoking, previous vascular disease

169
Q

What would an arterial ulcer look like ?

A

Punched out and deep, irregular shape, unsealing wound bed, thin shiny skin.

170
Q

Which type of ulcer would you tx with; revascularisation, anti-lately meds and mx of risk fx ?

A

Arterial

171
Q

Which ulcer is located on plantar aspect of foot, tip of toe, lateral to 5th metatarsal ?

A

Neuropathic diabetic

172
Q

What are the characteristics of neuropathic diabetic ulcers ?

A

Deep, surrounded by callus, insensate. Dry and cracked.

173
Q

What is the tx for a neuropathic diabetic ulcer ?

A

Off loading of pressure, topical growth fx

174
Q

Which ulcer is located on bony prominences and heels that is deep in appearance with atrophic skin and loss of muscle mass ?

A

Pressure ulcer

175
Q

How would you tx a pressure ulcer ?

A

off loading of pressure, reducetion of excessive moisture, shear and friction limit. Adequate nutrition.

176
Q

What is the normal process of wound healing ?

A

Cut/burn initiates immune response where wound becomes inflamed to prevent infection. New cells then form over wound and finally scar tissue forms to heal it.

177
Q

What are the causes of slowed wound healing ? (5)

A

DM, low growth hormone, Rheumatoid arthritis, vascular/arterial disease, Zn def

178
Q

When is the HbA1c result unreliable ?

A

If px has an abnormal RBC lifespan , abnormal haem/thalassaemia present

179
Q

What do the different levels of ABI indicate ?

A 
1-1.4 = calcification/hardening 
0.9-1 = acceptable 
0.8 - 0.9 = some arterial disease
0.5 - 0.8 = moderate disease 
<0.5 severe arterial disease
180
Q

What is the dx criteria for HHS?

A

hyperosmolar hyperglycaemic state.
Hypovoloemia, marked hyperglycaemia (>30 mmol/L) , no hyperketonuria (<3 mmol/L) , no acidosis (pH > 7.3 , HCO3 >15 mmol/L) , osmolarity usually >320 mosmol/Kg.

181
Q

What are the sx of HHS ?

A

Thirst (polydipsia) , urination (polyuria) , hunger (polyphagia)
May also have neurological signs, motor abnormalities etc.

182
Q

What are the triggers of HHS ? (5)

A

Infection, stroke, MI, trauma, certain meds

183
Q

What medication puts px at ^ risk of HHS?

A

Glucocorticoids, b blockers, CCBs, thiazide diuretics

184
Q

What is the BG reading during hypoglycaemia and what are the 3 general sx seen ?

A

<4 mmol/L

Autonomic , Neuroglyptic, general malaise

185
Q

What autonomic sx are seen during HHS ?

A

Sweating, palpitations, shaking, hunger

186
Q

What are the common chronic macrovascsular complications for diabetics and what risk are they compared with regular population ?

A

Ischaemic HD, cerebrovascular disease, peripheral vascular disease
Diabetics are at 2-6 x more risk

187
Q

What are the common trauma sites for diabetic foot ulcers ?

A

Back of heel, plantar metatarsals, great toe

188
Q

What happens during wound healing for a diabetic px ?

A

uncontrolled covalent bonding of aldose sugars to protein or lipid without any normal glycoslyation enzymes. AGEs ^ over cell membranes , structural/circulating proteins and ECM (turnover down)

189
Q

What is the action of AGEs on wound healing ?

A

Advanced glycosylation end products.

Alter properties of matrix proteins through covalent bonds/cross linking.

190
Q

What matrix proteins does AGEs act on ?

A

Collagen, vitronectin, laminin

191
Q

What is the action of AGEs on type 1 and 3 collagen ?

A

Type 1; AGE cross linking causes stiffness (same with elastin)
Type 3; AGE ^synthesis of type 3 which ^granulation tissue formation

192
Q

What is the effect of NO?

A

maintains BV diameter and BF to tissues. Regulates angiogenesis.

193
Q

How are NO levels altered in a diabetic px ?

A

^NO synthase inhibitor so less NO formed from L-arginine. ^G, kidney dysfunction, DKA which further decrease production.

194
Q

How does normal healing occur in relation to ECM?

A

ECM laid down -> degradation and remodelling forms mature tissue with ^tensile strength.

195
Q

How is healing different in diabetic ulcers in relation to protease activity ?

A

Proteases (MMPs) degrade ECM so less ; fibroblast and keritinocyte migration, tissue reorganisation, inflammation and remodelling of tissue

196
Q

Which proteases show ^expression in chronic diabetic non healing ulcers ?

A

MMP 2 and 9

Matrix metalloproteinases

197
Q

What is the function of growth factor in wound healing ?

A

Promote switching of early inflammatory phase to granulation tissue formation. Decreased in diabetics so lower TGF-b ^MMP

198
Q

What are the classes of diabetic foot ulcers ?

A

0, no ulcer in high risk foot
1, superficial ulcer. skin but no underlying tissue
2, deep to ligaments/muscle but no bone or abscess formed
3, deep with cellulitis/abscess forms. Often with osteomyelitis.
4, localised gangrene
5, Extensive gangrene involving whole foot

199
Q

How is microvascular disease explained in the metabolic pathway ?

A

genetic determinants and independent accelerating fx (HT, hyperlipidemia) lead to hyperglycaemia and diabetic tissue damage

200
Q

What is the pathophysiology of nephropathy ?

A

GFR^ soon after dx from poor glycaemic control. As kidneys damage ^ afferent arteriole dilates > efferent so ^intraglomerular filtration P -> ^damage to glomerulus.

201
Q

How does glomerular sclerosis arise ?

A

^Pressure leads to ^local shear force causing mesangial cell hypertrophy and ^secretion of ECM materials –> glomerular sclerosis

202
Q

How would you assess albuminuria and what does it predict ?

A

Small so undetectable on dipstick, needs immunoassay

Predictive marker of progression to nephropathy in T1D and ^CV risk in T2DM.

203
Q

What does ^plasma creatinine show ?

A

Later feature of albuminuria that progresses inevitably to renal failure. Although rate of progression differs in individuals.

204
Q

What are the stages of diabetic nephropathy ?

A
  1. hyperfiltration ^BF through kidney. Early renal hypertrophy
  2. Glomerular lesions without clinically evident disease
  3. Incipient nephropathy with microalbuminuria. alb/cr ratio 30-300 mg/day or albumin 20-200 mcg/min
  4. Overt D nephropathy with proteinuria >500mg/24hr. Creatinine clearance <70 ml/min
  5. End stage renal disease. Creatinine clearance <15
205
Q

How does the GFR change throughout the stages of diabetic nephropathy ?

A
  1. > 90
  2. 60-89
  3. 30-59
  4. 15-29
  5. <15
206
Q

How would you manage D nephropathy ?

A

BP <130/80 slows rate of deterioration. ACEi/ARB first line. Avoid oral hypoglycaemic meds (excreted by kidneys)

207
Q

What is the metabolic cause of neuropathy ?

A

Hyperglycaemia ^sorbitol and fructose in Schwann cells -> disrupts function and structure of cells

208
Q

What are the early functional changes in diabetic nerves ?

A

Delayed condition, segmental demyelination through Schwann cell damage. Axons are preserved (so damage can be reversed)

209
Q

What happens in late stage neuropathy ?

A

Axon damage (irreversible) leading to variety of neuropathies.

210
Q

What is symmetrical sensory polyneuropathy ?

A

Most common D neuropathy. Sx begin distal move toward calf. May appear in hands ‘stocking glove’ sensory loss. Pain, abnormal sensation, loss of vibration, thermal sense loss, walking on ‘cotton wool’, loss of balance

211
Q

Px presents with burning pain in feet, shins and ant thigh. Worse at night, they have to take off pyjamas.

A

Acute painful neuropathy

212
Q

When does acute painful neuropathy present ?

A

May present at dx after sudden improvement in diabetic control. Remits after 3-12 months if good control continued

213
Q

What drugs can be used for acute painful neuropathy ?

A

Duloxetine (1st line) , tricyclics (Amitriptyline)

214
Q

What is the cause of mononeuropathy and monoeuritis multiplex ?

A

CN and isolated peripheral nerve lesions. Onset is typically abrupt and painful

215
Q

What effect can mononeuropathy have on the eye ?

A

Isolated palsies of nerves to external eye (esp CN 3 and 6) common.

216
Q

68 diabetic man presents with wasting of his quads and reduced reflex at the knee, very tender. What is your dx?

A

Diabetic amyotrophy

CSF protein content elevated. Assoc with poor glycaemic control at dx, often resolves with mx

217
Q

What are the sx of autonomic neuropathy in relation to CV, GI, bladder and genitals ?

A

CV; tachycardia at rest, valsalva manoeuvre impaired. Postural hypotension (loss of sympathetic tone to peripheral arterioles)
GI; vomit (gastroparesis). diarrhoea at night
Bladder; loss of tone, incomplete emptying/stasis (infection).
Erectile dysfunction.

218
Q

What size tuning fork would you use for testing vibration perception ?

A

128 Hz (big boy)

219
Q

What Is the difference between initial screening and a diagnostic test ?

A

Screening; not a diagnostic, it identifies people who require further investigation. ‘Healthy who may have ^chance of condition’
Dx test; info, further tests and tx to decrease assoc problems or complications

220
Q

What is the sensitivity of a test ?

A

The ‘true positive’. Proportion of people who have a disease that test +ve (a/a+c)

221
Q

What is the specificity of a test ?

A

The ‘true negative’. Proportion of people how don’t have a disease that test -ve (d/b+d)

222
Q

What test should you use when calculating prevalence ?

A

The gold standard (GS) as opposed to a given screening test

223
Q

What is the PPV?

A

Positive predictive value. Probability that px with +ve screen result has disease. (a/a+b)

224
Q

What is calculated using d/c+d ?

A

Negative predictive value (NPV). Probability that px with -ve result doesn’t have disease

225
Q

What happens to the PPV when prevalence in a given population is lower ?

A

The PPV will decrease.

test (14 decks)

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