PBL4

Question 1

iscoemic forearm test

Answer 1

a test used in the differential diagnosis of metabolic causes of muscle weakness, fatigue and cramps – can be used to test for mcardles

Question 2

muscle biopsy

Answer 2

this a procedure that removes a small sample of muscle tissue

Question 3

creatine kinase

Answer 3

this is an important in enzymes, it is a maker of MI, catalyses the conversion of creatine and utilizes ATP to create phosphocreatine

Question 4

myoglobin

Answer 4

single polypeptide, it is an iron and oxygen binding protein that is found in muscle tissue, it has a higher affinity for oxygen than haemoglobin

Question 5

iV bolus

Answer 5

this is a large volume of fluid or dose or test substance that is given IV and rapidly

Question 6

dextrose

Answer 6

– a from of glucose, used by diabetetics to quickly increase there blood glucose levels

Question 7

second wind

Answer 7

thisis an exercise phenomen, person with Mcardles as too work up to intense exercise they cannot just do intense exercise

Question 8

ketogermic diet

Answer 8

this is a high fat, adquaete protein and low carb diet that is used to make the body burn fats rather than carbs

Question 9

AGSD

Answer 9

this is the association for glycogen storage disease, this is a support group for those that have glycogen storage disease and their families

Question 10

heteronormativity

Answer 10

this is the belief that people fall into distinct genders that have natural roles in life, believe that heterosexuality is the norm in life

Question 11

Hers disease

Answer 11

this is an autosomal recessive disorder, this effects glycogen storage in the liver, means that it is hard to control your blood glucose levels

Question 12

describe discrimination statistics

Answer 12

• 1/5 people in LBGT have experienced a hate crime or incident in the last 12 months
• 2/5 trans people have experienced a hate crime in the last 12 months
• 4/5 hate crimes go unreported
• Number of hate crimes have risen by 78% percent
• 3/10 avoid streets as they don’t want to be attacked

Question 13

what his the similarities and differences between Hers and Mcardles

Answer 13

• McArdle’s is to do with ineffective glycogen storage in the muscles whereas Hers is ineffective glycogen storage in the liver
• McArdle’s – these peope have to do second wind in order to be able to get to intense exercise whereas Hers can just exercise
• Hers cannot control blood glucose levels whereas McArdle can, they have to monitor their sugar levels
• Muscle biopsy is used to diagnose McArdle’s
• McArdles – symptoms are usually apparent before aged 10 but diagnosis is not till they are 30
• There is no treatment in mcardles apart from take gentle regular aerobic exercise
• Treatment in Hers includes frequient small meals and uncooked cornstartch to normalise blood glucose
• They are both glycogen storage diseases
• They are both autosomal recessive
• Hers is rarer
• Glycogen phosphorylase deficnet
• Liver phosphorylase deficiency

Question 14

what is 2nd wind

Answer 14

• 2nd wind is a sudden decrease in heart rate and an improved exercise tolerance occuring after a few minutes in exercise
• Depends on a number of factors including things from exercise intensity to frequency
• Takes around 10-25 minutes

Question 15

what is the role of glycogen in glucose metabolism

Answer 15

• Glucagon and adrenaline causes the activation of this enzyme
• Binds to receptors
• Activates adenyl cyclase
• This converts ATP to cAMP
• cAMP activates PKA this activates phosphorylase kinase
• which activates glycogen phosphorylase
• enzyme mutated and therefore stops this from happening
• therefore glycogen does not breakdown into glucose

Question 16

what is the genetics of Hers

Answer 16

• It is an autosomal recessive trait
• There is a lack of the enzyme liver phosphorylase
• This means that energy derived from glycogen accumulates in the liver
• There are mutations to the liver glycogen phosphorylase gene PYGL gene which is located on the Q arm of chromosome 14

Question 17

what is the genetics of McArdles

Answer 17

• An autosomal recessive disease
• There is two types this is the childhood onset and adult onset
• The gene for myophosphorylase PYGM is located on chromosome 11q13
• 95 different mutations
• Myophosphorylase consist of 842 amino acids
• Myophosphorylase is the form of glycogen phosphorylase that is found in the muscles

Question 18

what is a ketogenic diet

Answer 18

• Allows the body to produce small fuel molecules called ketone which is an alternative food source for the body when blood sugar is in short supply
• Liver produces ketones from fats, these can then be used as an energy supply
• They are especially used in the brain
• Body switches its fuel supply to be running mostly on fat
• When insulin levels become low fat burning increases dramatically
• Causes weight loss

Question 19

what lifestyle changes are required for Hers

Answer 19

• Frequent small meals
• Uncooked corn-starch
• Avoid prolonged fasting
• Have a high carbohydrate diet
• Trys to normalise blood glucose

Question 20

what lifestyle changes are required for McArdles

Answer 20

• Take regular aerobic exercise
• Ketogenic diet
• Increase other metabolic stores that is not glucose
• Work up to intense exercise do not go straight into intense exercise
• Vitamin B6 supplements
• Eat and drink certain amounts of sugar before exercise
• Diet high in protiens
• Don’t take mediciens such as statins
• Creatine supplemtns
• Carbohydrate rich diet

Question 21

what are the blood test result explanations

Answer 21

Creatine kinase is high – this indicates skeletal muscle damage, this maintains the phosphocreatine concentration and therefore the level of ATP under the condition of reduce energy availability. Need it for excess ATP
Myoglobin is high – needs to bind to oxygen, has a higher affinity for oxygen in order to be able to do aerobic respiration, muscle tissue breaks down and this release myoglobin which can cause temporary kidney failure
Potassium is high – impaired sacrolemmal function is associated with increase potassium relase
Urea is high – inhibited ATP production leads to the production or purine metabolism, these are converted to uric acid which can lead to hyperureamia

Question 22

what are the genes involved in McArdles disease

Answer 22

R50X mutation of PYGM gene

PYGM encodes instructions for muscle glycogen phosphorylase/myophosphorylase synthesis

Question 23

what happens when you continue exercise with McArdles disease

Answer 23

• with continued activity the body begins to break down muscle - this is called rhabdomyolysis
• muscle damage → release of myoglobin and CK into circulation
  Myoglobin filtered by kidneys into urine – red/brown urine
  Myoglobin release can lead to kidney damage as it precipitates in renal tubules, obstructing urine formation

Question 24

how does 2nd wind work

Answer 24

TP stored in the muscles (via phosphocreatine shuttle) supplies the first 10 sec worth of energy during short bursts of exercise
When ATP is used up, the body moves to anaerobic and aerobic metabolism
Anaerobic metabolism – provides energy for high-intensity bursts of activity but in McArdle’s this pathway is unavailable
Painful cramps within first few mins of exercise
Aerobic metabolism – low-intensity longer duration activity
Kicks in 7-8mins later as time is needed for blood to transport O2, fatty acids to exercising muscles

Question 25

describe the diagnosis and investigation of McArdkels

Answer 25

Muscle biopsy (diagnostic)
Central + subsarcolemmal accumulation of glycogen in vacuoles
Absence of functional myophosphorylase –seen using phosphorylase stain 

Serum creatine kinase (CK)
Enzyme found in heart, brain, skeletal muscle
Increased amounts released when there is muscle damage
Rhabdomyolysis
Intramuscular injection/EMG
MI

People with McArdle’s disease have raised CK – important to establish baseline
Basal levels may be 2000-2500iu/l (normal levels <190)
Can be much higher up to 100,000iu/l in case of rhabdomyolysis

Question 26

what is an ischaemic forearm test

Answer 26

• Venous blood samples taken for estimation of lactate and ammonia at rest and at 1, 2, 4, 6 and 10 minutes after a one minute period of repetitive maximum contractions of forearm flexor muscles
• Expect 2-3X increase in [lactate] within first 2 min after exercise
• However, no rise of lactate/ absence of lactate if there are defects in glycogenolysis / glycolysis

Question 27

describe pH in McArdles

Answer 27

Likely to be normal or raised

Lactate production usually reduced or absent if there are defects in glycogenolysis

Question 28

what is emergency management of McArdles

Answer 28

Patient presents very unwell following physical activity

• Urgent assessment for rhabdomyolysis (CK, urinalysis)
• IV bolus of saline, followed by 2x IV saline (maintenance) and 10% dextrose to keep blood glucose >3.5mmol/l
• Monitor urine output, CK, electrolytes

Potential complications

• Acute kidney injury – prompt referral for haemodialysis
• Compartment syndrome due to muscle swelling – surgical intervention

Question 29

what is the long term management of Mcardles

Answer 29

Moderate aerobic exercise e.g. walking

Recommended 150min/week in 30 min bouts to achieve second wind

Avoid heavy exertion and limit anaerobic exercise e.g. lifting heavy weights to no more than 6 seconds at a time

Avoid statins –risk of rhabdomyolysis (albeit very low)

Diets – important to have a carbohydrate rich diet

Pre-exercise sucrose may ease symptoms in first 15mins
Also ketogenic diet – deprive body of carbohydrates to enter a state of ketosis → liver to produce ketone bodies (from acetyl-CoA)