Met2 Flashcards
- Glyn could potentially take part in a long distance walk using blood glucose and free fatty acids as sources of energy. It might be expected that increasing free fatty acid delivery to muscles in people with McArdles would lead to increased energy production, but it does not. Why does this not happen? [2 marks]
There is limited availability of TCA intermediates because of limited pyruvate production (cannot break down glycogen) (1 mark) to react with acetyl CoA released from beta oxidation of fatty acids (1 mark).
- What are the differences between the causes of McArdles and Hers diseases. What would be the primary symptom on Hers disease? [3 marks]
- McArdles is caused by the lack of muscle glycogen phosphorylase enzyme in muscle cells [1]
- whereas Hers disease is caused by the lack of the same enzyme but in the liver [1].
- Hers disease results in hypoglyceamia or inability to control blood sugar OR enlarged liver [1 mark]
- The concentration of which two intracellular factors link muscle contraction to glycogen breakdown? [2 marks]
Calcium [1] & AMP levels [1]
- (I) What would you expect the pH to be if measured in the blood of a sprint athlete right after exercise?
(ii) Explain why?
(iii) On her admission to A&E, Glyn’s results show no change in pH. Explain why? [3 marks]
I) pH would be lowered (acidosis) [1]
Ii) High level of lactic acid in the blood [½], produced by anaerobic metabolism [½]
Iii) There is little to no lactate produced as there is no glucose source* in the muscle (*glycogen cannot be used) [1]
explain causes of McArdles disease
- Mutation in gene for myophosphorylase (PYGM) on chromosome 11
- Results in having no glycogen phosphorylase to break down the glycogen storage in their muscle.
- Unable to release glucose from glycogen in muscle
- Instead: during aerobic activity, skeletal muscle derives energy from free fatty acids by oxidising them in mitochondria via the beta oxidation pathway to form acetyl co-A. Acetyl co-A goes into the Krebs cycle, leads to production of ATP
symptoms & inheritance of McArdles disease?
-
Inheritance:
- Autosomal recessive: need both copies of gene to have mutation
-
Symptoms:
- Presentations occur in first decade, but often only diagnosed until rd or 4th decade
- Reversible exercise intolerance
- Fatigue
- Fixed motor weakness
- Acute crisis: severe fatigue and painful muscle cramps triggered by static muscle contractions (lifting weights) or dynamic exercise
- Second wind: after about 8 minutes most patients can continue exercise without difficulty
- Symptoms worsen with age as aerobic fitness is reduced
- Half of all patients have myoglobinuria (dark urine) following intense exercise
how do diagnose McArdles?
- Creatine kinase levels elevated
- Blood urate levels raised (uric acid): nitrogen from increased proteins break down (damaged cells)
- DNA testing
- Muscle biopsy
- No increase in venous lactic acid after exercise: blood pH levels also don’t decrease
- Urine myoglobinuria
- *Biopsy**
- Shows evidence of glycogen build up in the muscle cells
Absence of enzyme myophosphorylase
how do u manage McArdles disease? :)
- Diet rich in protein / keto diet: burning fatty acids instead of glucose into Krebs cycle. Have this enzyme (unlike glycogen phosphorylase)
- Creatine supplements: increases ATP levels.
- High blood sugar diet
explain causes of Hers disease
- Mutation in the PYGL gene: codes for glycogen phosphorylase
- glycogen phosphorylase: converts glycogen glucose-1-phosphate
- glycogen phosphorylase only found in liver cells
- As a result: glycogen builds up in the liver cells: hepatomegaly.
inheritance, symptoms, diagnosis and treatment of hers?
-
Inheritance:
- Autosomal recessive
-
Symptoms
- Hepatomegaly (enlarged liver)
- Increased hepatic glycogen content
- Hypoglycaemia (low blood sugar)
- Lactic acidosis (increase in lactic acid in the body)
- Faintness
- Weakness
- Delayed puberty
- Failure to thrive
-
Diagnosis:
- Genetic testing of PYGL gene
-
Treatment / Management:
- Avoid going for long times without eating / lots of small meals glycogen is only broken down in periods of need / hunger
- Eat high protein diet
- Monitor blood glucose levels
in McArdles disease, what is fixed muscle weakness and myoglobinuria? why do they occur? [3]
Fixed muscle weakness = permanent weakness to muscle occurs in 25% of individuals
Myoglobinuria = episodes of myoglobin in blood urine occurs in 50% of individuals.
Result of breakdown of skeletal muscle (rhabdomyolysis).
explain why a second wind occurs after 10 mins of excercise in mcardles disease?
Second Wind Phenomenon = a sudden, marked improvement in the tolerance to aerobic, dynamic, large muscle mass exercise (walking or cycling) after about 10 min.
Within the first few minutes of exercise, muscles rely mainly on muscle glycogen, causes patients with McArdle’s severe damage as there is not enough glucose/fat being supplied in the blood
Gradually, vessels vasodilate allowing glucose and fats (free fatty acids) to be used
Achieving second wind can be shortened by administering glucose in blood transfusions.
NOTE: can do intense activity up to 6 seconds due to small store of ATP and phosphocreatine (anaerobic) immediately available. However, this rapidly runs out= glycogen needs to be used and this is not possible.
what is sliding filament theory of McArdles disease?
Muscle remains contracted as without ATP the myosin heads remain attached to the actin forming cross bridges and maintaining the muscle in a contracted state. ATP is required to remove myosin heads from actin.
what is the funciton of myoglobin? [1]
where is it found? [1]
Myoglobin: found only in muscles. It functions as an oxygen-storage unit, providing oxygen to the working muscles. Only found in the blood if there is muscle damage.
