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Year 2 Medicine > Clinical Biochemistry; Musculoskeletal System > Flashcards

Clinical Biochemistry; Musculoskeletal System Flashcards

1
Q

Muscle Disease

  • Skeletal muscle can be affected by several diseases e.g. …, inflammation, metabolic … (genetic/acquired), non-metabolic … etc.
  • Biochemical Markers of muscle damage:
    • Creatine Kinase (CK) - the … … used, s…
    • Lactate … (LDH), myoglobin, AST, Troponin, other enzymes
A
  • Skeletal muscle can be affected by several diseases e.g. trauma, inflammation, metabolic myopathies (genetic/acquired), non-metabolic myopathies etc.
  • Biochemical Markers of muscle damage:
    • Creatine Kinase (CK) - the most widely used, sensitive
    • Lactate Dehydrogenase (LDH), myoglobin, AST, Troponin, other enzymes
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2
Q

What is the main biochemical marker of muscle damage?

A
  • Creatine Kinase (CK) - the most widely used, sensitive
  • Others include: Lactate Dehydrogenase (LDH), myoglobin, AST, Troponin, other enzymes
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3
Q

Why is Creatine Kinase (CK) the main biomarker of muscle damaged?

A

the most widely used, sensitive

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4
Q

Some causes of skeletal muscle disease (taken from Marshall Clin Chem)

A
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5
Q

Physical inj./ external agents - Causes of skeletal muscle diseases (7)

A
  • Crush syndrome
  • Ischaemic damage
  • Snake venoms
  • Statins
  • Steroids
  • Fibrates
  • Chloroquine
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6
Q

Inflam/Infection - Causes of skeletal muscle disease

A
  • Poly-, dermato-myositis, viral/bacterial, inclusion body myositis
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7
Q

Metabolic - Causes of Skeletal Muscle diseases

  • Assoc. with endocrine diseases: hypo/hyper…, hyper…, acro…
  • Genetic: ,,, metab. dis.( e.g. phosphorylase def.), fatty acid … dis. (acyl- CoA dehydrogenase def.), … chain dis. (mitochondrial dis.)
  • Other: C…, ethanol, nutritional
A
  • Assoc. with endocrine diseases: hypo/hyperthyroidism, hyperadrenalism, acromegaly
  • Genetic: carbohydrate metab. dis.( e.g. phosphorylase def.), fatty acid oxidation dis. (acyl- CoA dehydrogenase def.), respiratory chain dis. (mitochondrial dis.)
  • Other: CKD, ethanol, nutritional
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8
Q

Non-metabolic (genetic) - Causes of Skeletal Muscle Diseases

  • Muscular …
  • D…
  • Becker … dystrophies
  • Periodic … (hyper & hypokalaemic)
A
  • Muscular dystrophies
  • Duchenne
  • Becker myotonic dystrophies
  • Periodic paralyses (hyper & hypokalaemic)
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9
Q

Other causes of skeletal muscle diseases include myopathy associated with … disease

A

myopathy associated with malignant disease

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10
Q

Terminology in muscle disease

A
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11
Q

Terminology in muscle disease

A

dystrophy - progressive abnormality

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12
Q

dystrophy - … abnormality

A

dystrophy - progressive abnormality

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13
Q

Causes of increased CK

  • >… x Upper Limit of Normal (ULN) : Often in polymyositis, rhabdomyolysis, Duchenne muscular dystrophy, myocardial infarction
  • …-… x ULN: Post-surgery, trauma, severe exercise, grand mal convulsion, myositis, carriers of Duchenne muscular dystrophy
  • < … x ULN: Physiological (related to muscle bulk e.g. weight lifters/athletes), hypothyroidism, drugs (e.g. statins – rare, 1 in 10,000)
A
  • >10 x Upper Limit of Normal (ULN) : Often in polymyositis, rhabdomyolysis, Duchenne muscular dystrophy, myocardial infarction
  • 5-10 x ULN: Post-surgery, trauma, severe exercise, grand mal convulsion, myositis, carriers of Duchenne muscular dystrophy
  • < 5 x ULN: Physiological (related to muscle bulk e.g. weight lifters/athletes), hypothyroidism, drugs (e.g. statins – rare, 1 in 10,000)
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14
Q

Causes of increased CK

  • >10 x Upper Limit of Normal (ULN) : Often in polymyositis, rhabdomyolysis, … muscular dystrophy, … infarction
  • 5-10 x ULN: Post-…, trauma, severe …, grand … convulsion, myositis, carriers of … muscular dystrophy
  • < 5 x ULN: Physiological (related to muscle bulk e.g. weight lifters/athletes), …thyroidism, drugs (e.g. … – rare, 1 in 10,000)
A
  • >10 x Upper Limit of Normal (ULN) : Often in polymyositis, rhabdomyolysis, Duchenne muscular dystrophy, myocardial infarction
  • 5-10 x ULN: Post-surgery, trauma, severe exercise, grand mal convulsion, myositis, carriers of Duchenne muscular dystrophy
  • < 5 x ULN: Physiological (related to muscle bulk e.g. weight lifters/athletes), hypothyroidism, drugs (e.g. statins – rare, 1 in 10,000)
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15
Q

Causes of increased CK

  • >10 x Upper Limit of Normal (ULN) : Often in poly…, …myolysis, Duchenne muscular dystrophy, myocardial infarction
  • 5-10 x ULN: Post-surgery, t…, severe exercise, g… m… convulsion, myositis, carriers of Duchenne muscular dystrophy
  • < 5 x ULN: Physiological (related to … … e.g. weight lifters/athletes), hypothyroidism, drugs (e.g. statins – rare, 1 in 10,000)
A
  • >10 x Upper Limit of Normal (ULN) : Often in polymyositis, rhabdomyolysis, Duchenne muscular dystrophy, myocardial infarction
  • 5-10 x ULN: Post-surgery, trauma, severe exercise, grand mal convulsion, myositis, carriers of Duchenne muscular dystrophy
  • < 5 x ULN: Physiological (related to muscle bulk e.g. weight lifters/athletes), hypothyroidism, drugs (e.g. statins – rare, 1 in 10,000)
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16
Q

Causes of increased CK

  • >.. x Upper Limit of Normal (ULN) : Often in polymyositis, rhabdomyolysis, Duchenne muscular dystrophy, myocardial infarction
  • 5-… x ULN: Post-surgery, trauma, severe exercise, grand mal …, myositis, carriers of …
  • < 5 x ULN: … (related to muscle bulk e.g. weight lifters/athletes), hypothyroidism, drugs (e.g. statins – rare, 1 in 10,000)
A
  • >10 x Upper Limit of Normal (ULN) : Often in polymyositis, rhabdomyolysis, Duchenne muscular dystrophy, myocardial infarction
  • 5-10 x ULN: Post-surgery, trauma, severe exercise, grand mal convulsion, myositis, carriers of Duchenne muscular dystrophy
  • < 5 x ULN: Physiological (related to muscle bulk e.g. weight lifters/athletes), hypothyroidism, drugs (e.g. statins – rare, 1 in 10,000)
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17
Q

What is Rhabdomyolysis?

A

Rhabdomyolysis is rapid destruction of striated muscle resulting in release of myoglobin and other muscle proteins and intracellular ions into the circulation

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18
Q

Rhabdomyolysis is rapid … of … muscle resulting in release of … and other muscle proteins and intracellular ions into the circulation

A

Rhabdomyolysis is rapid destruction of striated muscle resulting in release of myoglobin and other muscle proteins and intracellular ions into the circulation

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19
Q

Skeletal muscle consists …% of body weight.

A

Skeletal muscle consists 40% of body weight.

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20
Q

Skeletal muscle consists …% of body weight. Therefore loss of integrity of cell membranes (reversible or irreversible) has a huge potential for loss of … (into muscle cells), potassium, phosphate, enzymes, proteins, and purines (into ECF).

A

Skeletal muscle consists 40% of body weight. Therefore loss of integrity of cell membranes (reversible or irreversible) has a huge potential for loss of water (into muscle cells), potassium, phosphate, enzymes, proteins, and purines (into ECF).

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21
Q

Causes of rhabdomyolysis

  • Severe …
  • … (trauma, electrocution, crush injuries, surgery)
  • I…
  • … (severe hypokalaemia or hypophosphataemia, malignant hyperpyrexia, McArdle disease, phosphofructokinase deficiency etc.)
  • Infections, T…, drugs
A
  • Severe exercise
  • Injury (trauma, electrocution, crush injuries, surgery)
  • Ischaemia
  • Metabolic (severe hypokalaemia or hypophosphataemia, malignant hyperpyrexia, McArdle disease, phosphofructokinase deficiency etc.)
  • Infections, toxins, drugs
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22
Q

Causes of rhabdomyolysis

  • … exercise
  • Injury (trauma, E…, C… injuries, surgery)
  • Ischaemia
  • Metabolic (severe ….kalaemia or hypophosphataemia, malignant hyperpyrexia, McArdle disease, phosphofructokinase deficiency etc.)
  • Infections, toxins, D..
A
  • Severe exercise
  • Injury (trauma, electrocution, crush injuries, surgery)
  • Ischaemia
  • Metabolic (severe hypokalaemia or hypophosphataemia, malignant hyperpyrexia, McArdle disease, phosphofructokinase deficiency etc.)
  • Infections, toxins, drugs
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23
Q

Rhabdomyolysis

  • Serum:
    • CK >… x ULN
    • …kalaemia
    • …uricaemia (from purines, nephrotoxic)
    • …phosphataemia
    • …calcaemia
    • Rise in [creatinine]>[…]
    • Metabolic acidosis (release of lactate and other acids)
  • Urine dip positive for peroxidase activity of myoglobulin
A
  • Serum:
    • CK >10 x ULN
    • Hyperkalaemia
    • Hyperuricaemia (from purines, nephrotoxic)
    • Hyperphosphataemia
    • Hypocalcaemia
    • Rise in [creatinine]>[urea]
    • Metabolic acidosis (release of lactate and other acids)
  • Urine dip positive for peroxidase activity of myoglobulin
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24
Q

Rhabdomyolysis

  • Serum:
    • … >10 x ULN
    • Hyperkalaemia
    • Hyperuricaemia (from P…, nephrotoxic)
    • Hyperphosphataemia
    • Hypocalcaemia
    • Rise in […]>[urea]
    • … acidosis (release of lactate and other acids)
  • Urine dip positive for peroxidase activity of myoglobulin
A
  • Serum:
    • CK >10 x ULN
    • Hyperkalaemia
    • Hyperuricaemia (from purines, nephrotoxic)
    • Hyperphosphataemia
    • Hypocalcaemia
    • Rise in [creatinine]>[urea]
    • Metabolic acidosis (release of lactate and other acids)
  • Urine dip positive for peroxidase activity of myoglobulin
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25
Q

Rhabdomyolysis

  • Serum:
    • CK >10 x ULN
    • Hyperkalaemia
    • Hyper… (from purines, nephrotoxic)
    • Hyperphosphataemia
    • Hypo…
    • … in [creatinine]>[urea]
    • Metabolic acidosis (release of lactate and other acids)
  • Urine dip … for peroxidase activity of myoglobulin
A
  • Serum:
    • CK >10 x ULN
    • Hyperkalaemia
    • Hyperuricaemia (from purines, nephrotoxic)
    • Hyperphosphataemia
    • Hypocalcaemia
    • Rise in [creatinine]>[urea]
    • Metabolic acidosis (release of lactate and other acids)
  • Urine dip positive for peroxidase activity of myoglobulin
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26
Q

Rhabdomyolysis

  • Serum:
    • CK >… x ULN
    • Hyperkalaemia
    • Hyperuricaemia (from purines, nephrotoxic)
    • Hyperphosphataemia
    • Hypocalcaemia
    • Rise in [creatinine]>[urea]
    • Metabolic acidosis (release of … and other acids)
  • Urine dip positive for … activity of …
A
  • Serum:
    • CK >10 x ULN
    • Hyperkalaemia
    • Hyperuricaemia (from purines, nephrotoxic)
    • Hyperphosphataemia
    • Hypocalcaemia
    • Rise in [creatinine]>[urea]
    • Metabolic acidosis (release of lactate and other acids)
  • Urine dip positive for peroxidase activity of myoglobulin
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27
Q

Renal failure in rhabdomyolysis

  • Myoglobin is NOT directly … but renal failure in rhabdomyolysis caused by:
    • Hypovolaemia
    • Metabolic … (hypovol., release of organic acids)
    • …uria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing physical obstruction)
    • …uricaemia (purine → urate and intrarenal deposition)
    • … increases urine concn and tubular obstruction by myoglobin casts, uric acid casts products
A
  • Myoglobin is NOT directly nephrotoxic but renal failure in rhabdomyolysis caused by:
    • Hypovolaemia
    • Metabolic acidosis (hypovol., release of organic acids)
    • Aciduria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing physical obstruction)
    • Hyperuricaemia (purine → urate and intrarenal deposition)
    • Dehydration increases urine concn and tubular obstruction by myoglobin casts, uric acid casts products
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28
Q

Renal failure in rhabdomyolysis

  • … is NOT directly nephrotoxic but renal failure in rhabdomyolysis caused by:
    • Hypov…
    • … acidosis (hypovol., release of organic acids)
    • Aciduria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing physical obstruction)
    • Hyperuricaemia (… → urate and intrarenal deposition)
    • Dehydration increases urine concn and tubular obstruction by myoglobin casts, uric acid casts products
A
  • Myoglobin is NOT directly nephrotoxic but renal failure in rhabdomyolysis caused by:
    • Hypovolaemia
    • Metabolic acidosis (hypovol., release of organic acids)
    • Aciduria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing physical obstruction)
    • Hyperuricaemia (purine → urate and intrarenal deposition)
    • Dehydration increases urine concn and tubular obstruction by myoglobin casts, uric acid casts products
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29
Q

Renal failure in rhabdomyolysis

  • Myoglobin is NOT directly … but renal failure in rhabdomyolysis caused by:
    • Hypovolaemia
    • Metabolic acidosis (hypovol., release of … acids)
    • Aciduria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing … obstruction)
    • Hyperuricaemia (purine → … and intrarenal deposition)
    • Dehydration increases urine concn and tubular obstruction by myoglobin casts, uric acid casts products
A
  • Myoglobin is NOT directly nephrotoxic but renal failure in rhabdomyolysis caused by:
    • Hypovolaemia
    • Metabolic acidosis (hypovol., release of organic acids)
    • Aciduria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing physical obstruction)
    • Hyperuricaemia (purine → urate and intrarenal deposition)
    • Dehydration increases urine concn and tubular obstruction by myoglobin casts, uric acid casts products
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30
Q

Renal failure in rhabdomyolysis

  • Myoglobin is NOT directly nephrotoxic but renal failure in rhabdomyolysis caused by:
    • Hypovolaemia
    • Metabolic acidosis (hypovol., release of organic acids)
    • Aciduria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing physical obstruction)
    • Hyperuricaemia (purine → urate and intrarenal deposition)
    • Dehydration increases urine … and tubular … by myoglobin casts, uric acid casts products
A
  • Myoglobin is NOT directly nephrotoxic but renal failure in rhabdomyolysis caused by:
    • Hypovolaemia
    • Metabolic acidosis (hypovol., release of organic acids)
    • Aciduria (causes myoglobin to convert to ferrihaemate, nephrotoxic, and precipitates causing physical obstruction)
    • Hyperuricaemia (purine → urate and intrarenal deposition)
    • Dehydration increases urine concn and tubular obstruction by myoglobin casts, uric acid casts products
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31
Q

Renal protection in rhabdomyolysis

  • Identify those at risk e.g. … age, higher …
  • Fluid status/BP etc – proactive management of hypovolaemia
  • Less common:
    • Mannitol – osmotic …
    • Urine alkalinisation – pHu >8 with bicarb infusion
    • Early haemofiltration
    • Note compartment syndrome is another complication of rhabdomyolysis
A
  • Identify those at risk e.g. older age, higher CK
  • Fluid status/BP etc – proactive management of hypovolaemia
  • Less common:
    • Mannitol – osmotic diuretic
    • Urine alkalinisation – pHu >8 with bicarb infusion
    • Early haemofiltration
    • Note compartment syndrome is another complication of rhabdomyolysis
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32
Q

Renal protection in rhabdomyolysis

  • Identify those at risk e.g. older age, higher CK
  • Fluid status/BP etc – proactive management of hypovolaemia
  • Less common:
    • m… – osmotic diuretic
    • Urine alkalinisation – pHu >… with bicarb infusion
    • Early haemo…
    • Note … syndrome is another complication of rhabdomyolysis
A
  • Identify those at risk e.g. older age, higher CK
  • Fluid status/BP etc – proactive management of hypovolaemia
  • Less common:
    • Mannitol – osmotic diuretic
    • Urine alkalinisation – pHu >8 with bicarb infusion
    • Early haemofiltration
    • Note compartment syndrome is another complication of rhabdomyolysis
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33
Q

Renal protection in rhabdomyolysis

  • Identify those at risk e.g. … age, higher CK
  • … status/… etc – proactive management of hypo…
  • Less common:
    • Mannitol – osmotic diuretic
    • Urine alkalinisation – pHu >8 with bicarb infusion
    • Early haemofiltration
    • Note compartment syndrome is another complication of rhabdomyolysis
A
  • Identify those at risk e.g. older age, higher CK
  • Fluid status/BP etc – proactive management of hypovolaemia
  • Less common:
    • Mannitol – osmotic diuretic
    • Urine alkalinisation – pHu >8 with bicarb infusion
    • Early haemofiltration
    • Note compartment syndrome is another complication of rhabdomyolysis
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34
Q

Renal protection in rhabdomyolysis

  • Identify those at risk e.g. older age, higher CK
  • Fluid status/BP etc – proactive management of hypovolaemia
  • Less common:
    • Mannitol – .. diuretic
    • Urine … – pHu >8 with bicarb infusion
    • … haemofiltration
    • Note … syndrome is another complication of rhabdomyolysis
A
  • Identify those at risk e.g. older age, higher CK
  • Fluid status/BP etc – proactive management of hypovolaemia
  • Less common:
    • Mannitol – osmotic diuretic
    • Urine alkalinisation – pHu >8 with bicarb infusion
    • Early haemofiltration
    • Note compartment syndrome is another complication of rhabdomyolysis
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35
Q

Biochemical investigation of muscle disease

  • Routine … studies (plasma s…, p…, chloride, urea, bicarbonate, glucose, calcium, phosphate, simple endocrine function tests)
  • Plasma creatine kinase activity
  • [Other enzymes (ALT, AST)]
  • … in urine, not offered anymore, serum CK is more …
  • Highly … biochemical investigations (carnitine, fatty acids, etc.)
A
  • Routine biochemical studies (plasma sodium, potassium, chloride, urea, bicarbonate, glucose, calcium, phosphate, simple endocrine function tests)
  • Plasma creatine kinase activity
  • [Other enzymes (ALT, AST)]
  • Myoglobin in urine, not offered anymore, serum CK is more sensitive
  • Highly specialised biochemical investigations (carnitine, fatty acids, etc.)
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36
Q

Biochemical investigation of muscle disease

  • Routine biochemical studies (plasma sodium, potassium, c…, u…, bicarbonate, glucose, calcium, phosphate, simple endocrine function tests)
  • Plasma … … activity
  • [Other enzymes (ALT, AST)]
  • … in urine, not offered anymore, serum CK is more …
  • Highly … biochemical investigations (carnitine, fatty acids, etc.)
A
  • Routine biochemical studies (plasma sodium, potassium, chloride, urea, bicarbonate, glucose, calcium, phosphate, simple endocrine function tests)
  • Plasma creatine kinase activity
  • [Other enzymes (ALT, AST)]
  • Myoglobin in urine, not offered anymore, serum CK is more sensitive
  • Highly specialised biochemical investigations (carnitine, fatty acids, etc.)
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37
Q

Other investigations for muscle disease (4)

A
  • Histological Studies
  • Immunocytochemical studies
  • Genetic analyses
  • EMG
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38
Q

Metabolic Muscle Diseases

  • 1-Disorders of … Metabolism
  • 2-Defects of … Chain (e.g. mitochondrial)
  • 3-Defects of … … oxidation (FAOD)
    • Defects are in enzymes involved in muscle metabolism leading to energy depletion or structural damage.
A
  • 1-Disorders of Carbohydrate Metabolism
  • 2-Defects of Respiratory Chain (e.g. mitochondrial)
  • 3-Defects of fatty acid oxidation (FAOD)
    • Defects are in enzymes involved in muscle metabolism leading to energy depletion or structural damage.
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39
Q

Metabolic Muscle Diseases

  • 1-Disorders of Carbohydrate Metabolism
  • 2-Defects of Respiratory Chain (e.g. mitochondrial)
  • 3-Defects of fatty acid oxidation (FAOD)
    • Defects are in enzymes involved in muscle … leading to energy … or … damage.
A
  • 1-Disorders of Carbohydrate Metabolism
  • 2-Defects of Respiratory Chain (e.g. mitochondrial)
  • 3-Defects of fatty acid oxidation (FAOD)
    • Defects are in enzymes involved in muscle metabolism leading to energy depletion or structural damage.
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40
Q

Symptoms of Metabolic Muscle Diseases

  • Symptoms vary; most present … in life (… to ..) and can be mild (… intolerance) to fatal:
  • Exercise intolerance, muscle pain (…) after exercise, cramps, muscle damage, myoglobinuria, rhabdomyolysis (..) leading to renal failure, proximal muscle weakness, …tonia, other organs may be affected e.g. heart, lungs
A
  • Symptoms vary; most present early in life (infancy to adolescence) and can be mild (exercise intolerance) to fatal:
  • Exercise intolerance, muscle pain (myalgia) after exercise, cramps, muscle damage, myoglobinuria, rhabdomyolysis (CK) leading to renal failure, proximal muscle weakness, hypotonia, other organs may be affected e.g. heart, lungs
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41
Q

Causes of metabolic muscle disease - 1

  • Disorders of Carbohydrate Metabolism
    • Chronic, … weakness with atrophy, cardio…, hepato…y, macroglossia, respiratory dysfunction
    • -Glycogen storage diseases (GSD): e.g. M… disease (GSD V, myophosphorylase deficiency) Pompe (GSD II, a-glucosidase deficiency)
A
  • Disorders of Carbohydrate Metabolism
    • Chronic, progressive weakness with atrophy, cardiomegaly, hepatomegaly, macroglossia, respiratory dysfunction
    • -Glycogen storage diseases (GSD): e.g. McArdle disease (GSD V, myophosphorylase deficiency) Pompe (GSD II, a-glucosidase deficiency)
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42
Q

Causes of metabolic muscle disease - 1

  • Disorders of Carbohydrate Metabolism
    • Chronic, progressive weakness with a…, cardiomegaly, hepatomegaly, macroglossia, r… dysfunction
    • -… … diseases (GSD): e.g. McArdle disease (GSD V, myophosphorylase deficiency) P.. (GSD II, a-glucosidase deficiency)
A
  • Disorders of Carbohydrate Metabolism
    • Chronic, progressive weakness with atrophy, cardiomegaly, hepatomegaly, macroglossia, respiratory dysfunction
    • -Glycogen storage diseases (GSD): e.g. McArdle disease (GSD V, myophosphorylase deficiency) Pompe (GSD II, a-glucosidase deficiency)
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43
Q

Causes of metabolic muscle disease - 1

  • Disorders of Carbohydrate Metabolism
    • C…, progressive weakness with atrophy, cardiomegaly, hepatomegaly, macro…, respiratory …
    • -Glycogen storage diseases (GSD): e.g. McArdle disease (GSD V, myophosphorylase deficiency) Pompe (GSD II, a-glucosidase deficiency)
A
  • Disorders of Carbohydrate Metabolism
    • Chronic, progressive weakness with atrophy, cardiomegaly, hepatomegaly, macroglossia, respiratory dysfunction
    • -Glycogen storage diseases (GSD): e.g. McArdle disease (GSD V, myophosphorylase deficiency) Pompe (GSD II, a-glucosidase deficiency)
44
Q

Causes of metabolic muscle disease -2

  • Defects of … … (Mitochondrial Enzyme deficiencies/myopathies)
  • … disorders; very variable. Muscle weakness, exercise intolerance, hearing loss, seizures, ataxia, pigmentary retinopathy, cardiomyopathy
A
  • Defects of Respiratory Chain (Mitochondrial Enzyme deficiencies/myopathies)
  • Multisystem disorders; very variable. Muscle weakness, exercise intolerance, hearing loss, seizures, ataxia, pigmentary retinopathy, cardiomyopathy
45
Q

Causes of metabolic muscle disease -2

  • Defects of Respiratory Chain (Mitochondrial … deficiencies/myopathies)
  • Multisystem disorders; very …. Muscle …, exercise …, … loss, seizures, ataxia, pigmentary retinopathy, cardio…
A
  • Defects of Respiratory Chain (Mitochondrial Enzyme deficiencies/myopathies)
  • Multisystem disorders; very variable. Muscle weakness, exercise intolerance, hearing loss, seizures, ataxia, pigmentary retinopathy, cardiomyopathy
46
Q

Symptoms of Respiratory Chain Disorders:
MELAS: mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes

  • Recurrent …-like episodes, …-like headaches, V… and S….
  • Other symp include: general muscle …, exercise …, hearing loss, D… and S… stature. … inheritance.
  • Others include MERRF, Kearns-Sayre.
A
  • Recurrent stroke-like episodes, migraine-like headaches, vomiting and seizures. Other symp include: general muscle weakness, exercise intolerance, hearing loss, diabetes and short stature. Maternal inheritance. Others include MERRF, Kearns-Sayre.
47
Q

Causes of metabolic muscle disease -3

  • Defects of … … oxidation (Lipid storage disorders)
  • Muscle … and …, myoglobinuria, exercise …
  • Symptoms usually present after prolonged period of exercise.
A
  • Defects of fatty acid oxidation (Lipid storage disorders)
  • Muscle weakness and pain, myoglobinuria, exercise intolerance.
  • Symptoms usually present after prolonged period of exercise.
48
Q

Causes of metabolic muscle disease -3

  • Defects of fatty acid oxidation (… storage disorders)
  • Muscle weakness and pain, myoglobinuria, exercise intolerance.
  • Symptoms usually present after … period of ….
A
  • Defects of fatty acid oxidation (Lipid storage disorders)
  • Muscle weakness and pain, myoglobinuria, exercise intolerance.
  • Symptoms usually present after prolonged period of exercise.
49
Q

Biochemical Abnormalities in Metabolic Muscle Diseases

  • Elevated C… (intermittent)
  • Elevated T…
  • …glycaemia
  • Abnormal L… (may be muscle damage)
  • …globinuria
  • Increased plasma L…
  • Increased C… & triglycerides
  • Increased plasma U…
  • A… acylcarnitines
A
  • Elevated CK (intermittent)
  • Elevated troponin
  • Hypoglycaemia
  • Abnormal LFTs (may be muscle damage)
  • Myoglobinuria
  • Increased plasma lactate
  • Increased cholesterol & triglycerides
  • Increased plasma urate
  • Abnormal acylcarnitines
50
Q

Biochemical Abnormalities in Metabolic Muscle Diseases - what tests?

A

Abnormalities may be present only during an attack

51
Q

Clinical Investigations - Biochemical abnormalities in metabolic muscle diseases

  • … history, n…, c…
  • *Gastrointestinal, Ophthalmology, a… (*mitochondrial)
A
  • Family history, Neurological, Cardiac
  • *Gastrointestinal, Ophthalmology, Audiology (*mitochondrial)
52
Q

Structural muscle disease: Duchenne muscular dystrophy

  • …-linked - dystrophin gene
  • … weakness, Progressive
  • …’s sign, hypertrophy, contractures
  • Lab - very high …, biopsy, genetic tests
A
  • X-linked - dystrophin gene
  • Proximal weakness, Progressive
  • Gower’s sign, hypertrophy, contractures
  • Lab - very high CK, biopsy, genetic tests
53
Q

Structural muscle disease: Duchenne muscular dystrophy

  • X-linked - d… gene
  • Proximal w…, p…
  • Gower’s sign, hypertrophy, contractures
  • Lab - very … CK, biopsy, genetic tests
A
  • X-linked - dystrophin gene
  • Proximal weakness, Progressive
  • Gower’s sign, hypertrophy, contractures
  • Lab - very high CK, biopsy, genetic tests
54
Q

Myaesthenia Gravis

  • Present with - Weakness, easy …
    • Especially cranial nerves - d.. and p…
  • Due to antibodies AChR
  • Occurs in young … OR a/w thymoma
A
  • Present with - Weakness, easy tiring
    • Especially cranial nerves - diplopia and ptosis
  • Due to antibodies AChR
  • Occurs in young women OR a/w thymoma
55
Q

Myaesthenia Gravis

  • Present with - Weakness, easy tiring
    • Especially … nerves - diplopia and ptosis
  • Due to antibodies A…
  • Occurs in young women OR a/w t…
A
  • Present with - Weakness, easy tiring
    • Especially cranial nerves - diplopia and ptosis
  • Due to antibodies AChR
  • Occurs in young women OR a/w thymoma
56
Q

Lambert-Eaton myaesthenic syndrome

  • Antibodies against the pre-synaptic voltage-gated … channels
  • Rare para…
A
  • Antibodies against the pre-synaptic voltage-gated calcium channels
  • Rare paraneoplastic
57
Q

Rheumatological disease

  • More limited role of biochemistry in rheumatology
      1. Drug monitoring -DMARDs, Cytotoxic agents, Biologics
      1. Bone … markers
      1. G…
      1. Vit …
      1. P… disease
A
  • More limited role of biochemistry in rheumatology
      1. Drug monitoring -DMARDs, Cytotoxic agents, Biologics
    • 2. Bone turnover markers
    • 3. Gout
    • 4. Vit D
    • 5. Paget’s disease
58
Q

Rheumatological disease

  • More limited role of biochemistry in rheumatology
      1. Drug monitoring -D…s, C… agents, B…
      1. … turnover markers
      1. Gout
      1. Vit D
      1. P… disease
A
  • More limited role of biochemistry in rheumatology
    • 1. Drug monitoring -DMARDs, Cytotoxic agents, Biologics
    • 2. Bone turnover markers
    • 3. Gout
    • 4. Vit D
    • 5. Paget’s disease
59
Q

Drug monitoring

  • DMARDs-m…:
    • measure … is a marker of liver fibrosis and serial measurements can indicate need for a liver biopsy in those on long term methotrexate.
  • Immunosuppressant –a…:
    • TPMT (thiopurine methyl transferase) metabolises azathioprine to 6-methylxantrhine (inactive). Thiopurines are also metabolites of azathioprine that are myelotoxic. If levels low you use a lower dose
A
  • DMARDs-methotrexate:
    • PIIINP (type III procollagen peptide) is a marker of liver fibrosis and serial measurements can indicate need for a liver biopsy in those on long term methotrexate.
  • Immunosuppressant –azathioprine:
    • TPMT (thiopurine methyl transferase) metabolises azathioprine to 6-methylxantrhine (inactive). Thiopurines are also metabolites of azathioprine that are myelotoxic. If levels low you use a lower dose
60
Q

Drug monitoring

  • D..-methotrexate:
    • PIIINP (type III procollagen peptide) is a marker of liver … and serial measurements can indicate need for a liver biopsy in those on long term methotrexate.
  • I… –azathioprine:
    • … metabolises azathioprine to 6-methylxantrhine (inactive). Thiopurines are also metabolites of azathioprine that are myelotoxic. If levels low you use a … …
A
  • DMARDs-methotrexate:
    • PIIINP (type III procollagen peptide) is a marker of liver fibrosis and serial measurements can indicate need for a liver biopsy in those on long term methotrexate.
  • Immunosuppressant –azathioprine:
    • TPMT (thiopurine methyl transferase) metabolises azathioprine to 6-methylxantrhine (inactive). Thiopurines are also metabolites of azathioprine that are myelotoxic. If levels low you use a lower dose
61
Q

Biologic monitoring

  • I… and Adalimumab for example
  • Levels can be measured and … to them can be detected.
  • Antibodies to these drugs prevent them ….
  • These analyses are available but, like TPMT, most of the use is within … practice not so much in rheumatology (evidence base is in … primarily).
A
  • Infliximab and Adalimumab for example
  • Levels can be measured and antibodies to them can be detected.
  • Antibodies to these drugs prevent them working.
  • These analyses are available but, like TPMT, most of the use is within gastroenterology practice not so much in rheumatology (evidence base is in gastro primarily).
62
Q

Bone Turnover Markers

  • A plethora, all have pitfalls including enzymes and crosslinks associated with C… etc.
  • Serum CTX and urinary NTX: osteo…
  • Serum bone ALP and PINP: osteo…
A
  • A plethora, all have pitfalls including enzymes and crosslinks associated with collagen etc.
  • Serum CTX and urinary NTX: osteolysis
  • Serum bone ALP and PINP: osteogenesis
63
Q

Features of Bone Turnover Markers (BTM)

  • Performance depends on:
    • … type (… versus urine)
    • Marker …
    • Affected by … (.. contains collagen), exercise, drugs, age, time of day
  • Uses include:
    • Monitoring therapy
    • Predicting fracture risk
    • Malignancy of bone
A
  • Performance depends on:
    • Sample type (serum versus urine)
    • Marker type
    • Affected by nutrition (food contains collagen), exercise, drugs, age, time of day
  • Uses include:
    • Monitoring therapy
    • Predicting fracture risk
    • Malignancy of bone
64
Q

Features of Bone Turnover Markers (BTM)

  • Performance depends on:
    • Sample type (serum versus urine)
    • Marker type
    • Affected by nutrition (food contains collagen), exercise, drugs, age, time of day
  • Uses include:
    • … therapy
    • Predicting … risk
    • … of bone
A
  • Performance depends on:
    • Sample type (serum versus urine)
    • Marker type
    • Affected by nutrition (food contains collagen), exercise, drugs, age, time of day
  • Uses include:
    • Monitoring therapy
    • Predicting fracture risk
    • Malignancy of bone
65
Q

Uses of bone turnover markers (3)

A
  • Uses include:
    • Monitoring therapy
    • Predicting fracture risk
    • Malignancy of bone
66
Q

Focus on P1NP and CTX (Bone turnover markers)

  • Probably the commonest 2…
  • CTX (carboxy-terminal collagen crosslinks):
    • Specific and sensitive indicator of bone r…, low if anti-r… agents e.g. bisphosphonate working.
  • P1NP (procollagen type I terminal peptide):
    • Bone f… marker, fairly good marker of osteo… (higher being better).
A
  • Probably the commonest 2…
  • CTX (carboxy-terminal collagen crosslinks):
    • Specific and sensitive indicator of bone resorption, low if anti-resorptive agents e.g. bisphosphonate working.
  • P1NP (procollagen type I terminal peptide):
    • Bone formation marker, fairly good marker of osteogenesis (higher being better).
67
Q

Osteoporosis in clinical chemistry

  • Diagnosis is via:
    • … and …
    • Laboratory investigations
      • FBC, ESR, Creatinine, U & E, LFT ,s, Ca, P, TFT, PTH, 25(OH)D
      • Bone … markers (formation and resorption)
      • If secondary causes suspected
        • G…, testosterone, O..
        • SPE, U-BJ/light chains etc, Coeliac screen, urine calcium, tryptase (systemic mastocytosis)
  • Radiology: D.., XR
A
  • Diagnosis is via:
    • History and Examination
    • Laboratory investigations
      • FBC, ESR, Creatinine, U & E, LFT ,s, Ca, P, TFT, PTH, 25(OH)D
      • Bone turnover markers (formation and resorption)
      • If secondary causes suspected
        • Gonadotrophins, testosterone, oestrogen
        • SPE, U-BJ/light chains etc, Coeliac screen, urine calcium, tryptase (systemic mastocytosis)
  • Radiology: DEXA, XR
68
Q

Osteoporosis in clinical chemistry

  • Diagnosis is via:
    • History and Examination
    • Laboratory investigations
      • FBC, ESR, Creatinine, U & E, LFT ,s, Ca, P, TFT, PTH, 25(OH)D
      • Bone turnover markers (F… and R…)
      • If secondary causes suspected
        • Gonadotrophins, …, …
        • SPE, U-BJ/light chains etc, … screen, urine …, tryptase (systemic mastocytosis)
  • Radiology: DEXA, XR
A
  • Diagnosis is via:
    • History and Examination
    • Laboratory investigations
      • FBC, ESR, Creatinine, U & E, LFT ,s, Ca, P, TFT, PTH, 25(OH)D
      • Bone turnover markers (formation and resorption)
      • If secondary causes suspected
        • Gonadotrophins, testosterone, oestrogen
        • SPE, U-BJ/light chains etc, Coeliac screen, urine calcium, tryptase (systemic mastocytosis)
  • Radiology: DEXA, XR
69
Q

Secondary Osteoporosis Causes

A
70
Q

Secondary Osteoporosis Causes

A
71
Q

Secondary Osteoporosis Causes

A
72
Q

Osteoporosis in clinical chemistry

  • Therapies can be A… or Anti… so BTM can support therapy monitoring (BMD not the most dynamic tool but frequency of DEXA can be guided by BTM)
  • BTM can tell you about adherence and also help prevent treatment complications e.g. … by supporting drug …
A
  • Therapies can be anabolic or antiresorptive so BTM can support therapy monitoring (BMD not the most dynamic tool but frequency of DEXA can be guided by BTM)
  • BTM can tell you about adherence and also help prevent treatment complications e.g. osteonecrosis by supporting drug holidays
73
Q

Osteoporosis in clinical chemistry

  • Therapies can be anabolic or antiresorptive so … can support therapy monitoring (BMD not the most dynamic tool but frequency of DEXA can be guided by …)
  • … can tell you about adherence and also help prevent treatment complications e.g. osteonecrosis by supporting drug holidays
A
  • Therapies can be anabolic or antiresorptive so BTM can support therapy monitoring (BMD not the most dynamic tool but frequency of DEXA can be guided by BTM)
  • BTM can tell you about adherence and also help prevent treatment complications e.g. osteonecrosis by supporting drug holidays
74
Q

Gout - affects …% of adults; aim to get urate

A

Gout - affects 1% of adults; aim to get urate <300 µmol/L

75
Q

Gout

  • 1% of adults; aim to get urate
  • Associated with HTN, insulin resistance, hypercholesterolaemia and acute attacks with alcohol
  • Two times more common in …
  • Mono/polyarticular …, tophi, increase in renal …
  • Secondary causes include …thyroidism, hyper…, d…, renal impairment etc…
A
  • 1% of adults; aim to get urate <300 µmol/L
  • Associated with HTN, insulin resistance, hypercholesterolaemia and acute attacks with alcohol
  • Two times more common in men
  • Mono/polyarticular arthritis, tophi, increase in renal stones
  • Secondary causes include hypothyroidism, hyperparathyroidism, diuretics, renal impairment etc…
76
Q

… is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium urate cystals)

A

Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium urate cystals)

77
Q

Urate

  • Urate is a by-product of … metabolism but can precipitate out in soft tissues, kidneys (renal …) and joints (… inflammation caused by monosodium urate …)
  • Solubility decreased by low pH, and lower temperatures and affected by concentration of other ions
  • Also some IMD (inherited metabolic diseases) of purine metabolism
  • A/W pre… and premature birth
A
  • Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium urate cystals)
  • Solubility decreased by low pH, and lower temperatures and affected by concentration of other ions
  • Also some IMD (inherited metabolic diseases) of purine metabolism
  • A/W preeclampsia and premature birth
78
Q

Urate

  • Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium urate cystals)
  • Solubility decreased by low …, and lower … and affected by … of other ions
  • Also some IMD (inherited … diseases) of purine …
  • A/W preeclampsia and … birth
A
  • Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium urate cystals)
  • Solubility decreased by low pH, and lower temperatures and affected by concentration of other ions
  • Also some IMD (inherited metabolic diseases) of purine metabolism
  • A/W preeclampsia and premature birth
79
Q

Urate

  • Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium … cystals)
  • Solubility … by low pH, and lower temperatures and affected by concentration of other ions
  • Also some IMD (inherited metabolic diseases) of purine metabolism
  • A/W preeclampsia and premature birth
A
  • Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium urate cystals)
  • Solubility decreased by low pH, and lower temperatures and affected by concentration of other ions
  • Also some IMD (inherited metabolic diseases) of purine metabolism
  • A/W preeclampsia and premature birth
80
Q

Urate

  • Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout … caused by monosodium urate cystals)
  • Solubility decreased by low pH, and lower temperatures and affected by concentration of other ions
  • Also some IMD (… …. diseases) of purine metabolism
  • A/W … and premature birth
A
  • Urate is a by-product of purine metabolism but can precipitate out in soft tissues, kidneys (renal stones) and joints (gout inflammation caused by monosodium urate cystals)
  • Solubility decreased by low pH, and lower temperatures and affected by concentration of other ions
  • Also some IMD (inherited metabolic diseases) of purine metabolism
  • A/W preeclampsia and premature birth
81
Q

Generation of Uric Acid

  • A… and F… blocks Xanthine oxidase which converts xanthine to uric acid
A
  • Allopurinol and Febuxostat blocks Xanthine oxidase which converts xanthine to uric acid - given as therapy for prevention of gout attacks
82
Q

Uric acid - Increased production:

  • Cell …, D…
  • D…, E… defects
A
  • Cell breakdown, Diet
  • Drugs, Enzyme defects
83
Q

Uric acid - Decreased Excretion:

  • Treatments P… & s… inhibit urate reabsorp in kidney
A
  • Treatments probenecid & sulphinpyrazone inhibit urate reabsorp in kidney
84
Q

Vitamin D

  • R… and O…
  • Osteomalacia – adult disease
    • Delay in mineralisation as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of long bone
      • … growth plate
      • … metaphysis
  • Proximal myopathy (vitamin D deficient patients)
A
  • Rickets and osteomalacia
  • Osteomalacia – adult disease
    • Delay in mineralisation as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of long bone
      • Widened growth plate
      • Widened metaphysis
  • Proximal myopathy (vitamin D deficient patients)
85
Q

Vitamin D

  • R… and O…
  • Osteo… – adult disease
    • Delay in M… as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of long bone
      • … growth plate
      • … metaphysis
  • Proximal myopathy (vitamin D deficient patients)
A
  • Rickets and osteomalacia
  • Osteomalacia – adult disease
    • Delay in mineralisation as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of long bone
      • Widened growth plate
      • Widened metaphysis
  • Proximal myopathy (vitamin D deficient patients)
86
Q

Vitamin D

  • R… and O…
  • Osteomalacia – adult disease
    • Delay in mineralisation as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of … bone
      • … growth plate
      • … metaphysis
  • Proximal myopathy (vitamin D deficient patients)
A
  • Rickets and osteomalacia
  • Osteomalacia – adult disease
    • Delay in mineralisation as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of long bone
      • Widened growth plate
      • Widened metaphysis
  • Proximal myopathy (vitamin D deficient patients)
87
Q

Vitamin D

  • R… and O…
  • Osteomalacia – adult disease
    • Delay in mineralisation as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of long bone
      • … growth plate
      • … metaphysis
  • Proximal … (vitamin D deficient patients)
A
  • Rickets and osteomalacia
  • Osteomalacia – adult disease
    • Delay in mineralisation as osteoid is laid down
  • Rickets – paediatric version
    • Main skeletal changes affects growing ends of long bone
      • Widened growth plate
      • Widened metaphysis
  • Proximal myopathy (vitamin D deficient patients)
88
Q

Osteomalacia Causes

  • … deficiency: Low intake plus inadequate sunlight exposure; Malabsorption
  • Abnormal … … …: Liver disease; Renal disease; Drugs (anticonvulsants)
  • Low …: Low intake / Excess losses ; Vitamin D dependent rickets type I and II
A
  • Vit D deficiency: Low intake plus inadequate sunlight exposure; Malabsorption
  • Abnormal vit D metabolism: Liver disease; Renal disease; Drugs (anticonvulsants)
  • Low phosphate: Low intake / Excess losses ; Vitamin D dependent rickets type I and II
89
Q

Osteomalacia Causes

  • Vit D deficiency: Low intake plus inadequate … exposure; M…
  • Abnormal vit D metabolism: L… disease; R… disease; Drugs (a…)
  • Low phosphate: Low intake / Excess losses ; Vitamin D dependent rickets type … and …
A
  • Vit D deficiency: Low intake plus inadequate sunlight exposure; Malabsorption
  • Abnormal vit D metabolism: Liver disease; Renal disease; Drugs (anticonvulsants)
  • Low phosphate: Low intake / Excess losses ; Vitamin D dependent rickets type I and II
90
Q

Diagnosis of Osteomalacia

  • Clinically present:
    • m…, B… pain, Proximal muscle … / myopathy
    • Alk phosphatase raised, [Ca2+] low/N, [PO42-] low/N
    • … zones in X-rays
      • (L:low, H:high, N: normal, VDR: vit D receptor)
A
  • Clinically present:
    • Malaise, Bone pain, Proximal muscle weakness / myopathy
    • Alk phosphatase raised, [Ca2+] low/N, [PO42-] low/N
    • Looser zones in X-rays
      • (L:low, H:high, N: normal, VDR: vit D receptor)
91
Q

Diagnosis of Osteomalacia

  • Clinically present:
    • Malaise, Bone pain, Proximal muscle weakness / Myo…
    • Alk … raised, [Ca2+] low/N, [PO42-] low/N
    • Looser zones in X-rays
      • (L:low, H:high, N: normal, VDR: vit D receptor)
A
  • Clinically present:
    • Malaise, Bone pain, Proximal muscle weakness / myopathy
    • Alk phosphatase raised, [Ca2+] low/N, [PO42-] low/N
    • Looser zones in X-rays
      • (L:low, H:high, N: normal, VDR: vit D receptor)
92
Q

Osteomalacia differentials

  • It is rare therefore consider differentials:
    • Other metabolic bone disease: Osteo… / PTH bone disease / Neoplastic
    • Proximal muscle weakness: PMR, Muscular …
    • Bone pain: P…, Rheumatological, L…, Myeloma
    • Unexplained fractures: O…, P… disease
    • Psychological illness
A
  • It is rare therefore consider differentials:
    • Other metabolic bone disease: Osteoporosis / PTH bone disease / Neoplastic
    • Proximal muscle weakness: PMR, Muscular dystrophy
    • Bone pain: Paget’s, Rheumatological, Leukaemia, Myeloma
    • Unexplained fractures: Osteoporosis, Paget’s disease
    • Psychological illness
93
Q

Osteomalacia differentials

  • It is rare therefore consider differentials:
    • Other metabolic bone disease: Osteoporosis / PTH bone disease / Neoplastic
    • Proximal muscle …: PMR, Muscular dystrophy
    • Bone …: Paget’s, Rheumatological, Leukaemia, Myeloma
    • Unexplained …: Osteoporosis, Paget’s disease
    • P… illness
A
  • It is rare therefore consider differentials:
    • Other metabolic bone disease: Osteoporosis / PTH bone disease / Neoplastic
    • Proximal muscle weakness: PMR, Muscular dystrophy
    • Bone pain: Paget’s, Rheumatological, Leukaemia, Myeloma
    • Unexplained fractures: Osteoporosis, Paget’s disease
    • Psychological illness
94
Q

Osteomalacia differentials

  • It is rare therefore consider differentials:
    • Other metabolic bone disease: Osteoporosis / P… bone disease / Neo…
    • Proximal muscle weakness: P…, Muscular dystrophy
    • Bone pain: Paget’s, r…, Leukaemia, Myeloma
    • Unexplained fractures: Osteoporosis, Paget’s disease
    • Psychological illness
A
  • It is rare therefore consider differentials:
    • Other metabolic bone disease: Osteoporosis / PTH bone disease / Neoplastic
    • Proximal muscle weakness: PMR, Muscular dystrophy
    • Bone pain: Paget’s, Rheumatological, Leukaemia, Myeloma
    • Unexplained fractures: Osteoporosis, Paget’s disease
    • Psychological illness
95
Q

Osteomalacia differentials

  • It is rare therefore consider differentials:
    • Other … bone disease: Osteoporosis / PTH bone disease / Neoplastic
    • … muscle weakness: PMR, Muscular dystrophy
    • … …: Paget’s, Rheumatological, Leukaemia, Myeloma
    • … fractures: Osteoporosis, Paget’s disease
    • Psychological illness
A
  • It is rare therefore consider differentials:
    • Other metabolic bone disease: Osteoporosis / PTH bone disease / Neoplastic
    • Proximal muscle weakness: PMR, Muscular dystrophy
    • Bone pain: Paget’s, Rheumatological, Leukaemia, Myeloma
    • Unexplained fractures: Osteoporosis, Paget’s disease
    • Psychological illness
96
Q

Paget’s Disease

  • 1st described by Sir James Paget in 1876
  • Focal disorder of bone R… ?Cause
  • Characterised by
    • … bone …
    • Initiated by increased … mediated resorption
  • Abnormal bone remodelling – weakened, disorganised, enlarged
  • Monostotic / polyostotic: pelvis, femur, tibia, skull, spine
  • Malignant complications: Sarcoma <1%
A
  • 1st described by Sir James Paget in 1876
  • Focal disorder of bone remodelling?Cause
  • Characterised by
    • Accelerated bone turnover
    • Initiated by increased osteoclast mediated resorption
  • Abnormal bone remodelling – weakened, disorganised, enlarged
  • Monostotic / polyostotic: pelvis, femur, tibia, skull, spine
  • Malignant complications: Sarcoma <1%
97
Q

Paget’s Disease

  • 1st described by Sir James Paget in 1876
  • Focal disorder of bone remodelling ?Cause
  • Characterised by
    • Accelerated bone …
    • Initiated by increased osteoclast mediated resorption
  • … bone remodelling – weakened, d…, e…
  • Monostotic / polyostotic: pelvis, femur, tibia, skull, spine
  • Malignant complications: S… <1%
A
  • 1st described by Sir James Paget in 1876
  • Focal disorder of bone remodelling ?Cause
  • Characterised by
    • Accelerated bone turnover
    • Initiated by increased osteoclast mediated resorption
  • Abnormal bone remodelling – weakened, disorganised, enlarged
  • Monostotic / polyostotic: pelvis, femur, tibia, skull, spine
  • Malignant complications: Sarcoma <1%
98
Q

Paget’s Disease

  • 1st described by Sir James Paget in 1876
  • Focal disorder of bone remodelling ?Cause
  • Characterised by
    • … bone turnover
    • Initiated by increased osteoclast mediated resorption
  • Abnormal bone remodelling – W…, disorganised, E…
  • Monostotic / polyostotic: pelvis, femur, tibia, skull, spine
  • Malignant complications: Sarcoma
A
  • 1st described by Sir James Paget in 1876
  • Focal disorder of bone remodelling ?Cause
  • Characterised by
    • Accelerated bone turnover
    • Initiated by increased osteoclast mediated resorption
  • Abnormal bone remodelling – weakened, disorganised, enlarged
  • Monostotic / polyostotic: pelvis, femur, tibia, skull, spine
  • Malignant complications: Sarcoma <1%
99
Q

Paget’s Disease: Features

  • Asymptomatic
    • Incidental finding on XR / LFT’s with raised ALP
  • Symptomatic
    • Bone p…
    • Bone e… / d…
    • D… joint disease
    • F…
    • Auditory complications
    • Neurological complications
    • Immobilisation hypercalcaemia
    • High output cardiac failure (multifactorial)
  • May be complicated by gout, and is a differential for metastases
A
  • Asymptomatic
    • Incidental finding on XR / LFT’s with raised ALP
  • Symptomatic
    • Bone pain
    • Bone enlargement / deformity
    • Degenerative joint disease
    • Fractures
    • Auditory complications
    • Neurological complications
    • Immobilisation hypercalcaemia
    • High output cardiac failure (multifactorial)
  • May be complicated by gout, and is a differential for metastases
100
Q

Paget’s Disease: Features

  • Asymptomatic
    • Incidental finding on XR / LFT’s with raised ALP
  • Symptomatic
    • Bone pain
    • Bone enlargement / deformity
    • Degenerative joint disease
    • Fractures
    • A… complications
    • N… complications
    • I… hypercalcaemia
    • High output cardiac failure (multifactorial)
  • May be complicated by g…, and is a differential for metastases
A
  • Asymptomatic
    • Incidental finding on XR / LFT’s with raised ALP
  • Symptomatic
    • Bone pain
    • Bone enlargement / deformity
    • Degenerative joint disease
    • Fractures
    • Auditory complications
    • Neurological complications
    • Immobilisation hypercalcaemia
    • High output cardiac failure (multifactorial)
  • May be complicated by gout, and is a differential for metastases
101
Q

Paget’s Disease: Features

  • Asymptomatic
    • Incidental finding on XR / LFT’s with raised ALP
  • Symptomatic
    • Bone pain
    • Bone enlargement / deformity
    • Degenerative … disease
    • Fractures
    • Auditory complications
    • Neurological complications
    • Immobilisation hyper…
    • High output … failure (multifactorial)
  • May be complicated by gout, and is a differential for m…
A
  • Asymptomatic
    • Incidental finding on XR / LFT’s with raised ALP
  • Symptomatic
    • Bone pain
    • Bone enlargement / deformity
    • Degenerative joint disease
    • Fractures
    • Auditory complications
    • Neurological complications
    • Immobilisation hypercalcaemia
    • High output cardiac failure (multifactorial)
  • May be complicated by gout, and is a differential for metastases
102
Q

Paget’s Disease: Features

  • Asymptomatic
    • Incidental finding on … / LFT’s with raised …
  • Symptomatic
    • Bone …
    • Bone … / deformity
    • Degenerative joint disease
    • Fractures
    • Auditory complications
    • Neurological complications
    • Immobilisation hypercalcaemia
    • High output cardiac failure (multifactorial)
  • May be complicated by gout, and is a differential for metastases
A
  • Asymptomatic
    • Incidental finding on XR / LFT’s with raised ALP
  • Symptomatic
    • Bone pain
    • Bone enlargement / deformity
    • Degenerative joint disease
    • Fractures
    • Auditory complications
    • Neurological complications
    • Immobilisation hypercalcaemia
    • High output cardiac failure (multifactorial)
  • May be complicated by gout, and is a differential for metastases
103
Q

Case study - MSK Biochem

  • What is indicated?
A
  • Hypothyroidism indicated - unifying diagnosis
  • Muscle conditions/symptoms with hypothyroidism are common (30-80%) – usually myalgia, weakness, cramps, fatigability and stiffness.
  • Get delay in tendon reflexes, proximal muscle weakness and rarely hypertrophy (legs, tongue).
  • CK 10-100*normal, no correlation to weakness. Rhabdomyolysis is rare.
  • Also some rare syndromic presentations
104
Q

Hypothyroidism and Muscle

  • Muscle conditions/symptoms with hypothyroidism are common (30-80%) – usually m…, w…, c…, f… and s….
  • Get delay in tendon …, proximal muscle weakness and rarely hyper… (legs, tongue).
  • CK …-…*normal, no correlation to weakness. R… is rare.
  • Also some rare syndromic presentations
A
  • Muscle conditions/symptoms with hypothyroidism are common (30-80%) – usually myalgia, weakness, cramps, fatigability and stiffness.
  • Get delay in tendon reflexes, proximal muscle weakness and rarely hypertrophy (legs, tongue).
  • CK 10-100*normal, no correlation to weakness. Rhabdomyolysis is rare.
  • Also some rare syndromic presentations
105
Q

Kocher-Debré-Sémélaigne syndrome; called Herculean appearance in children.

  • Kocher Debre Semelaigne syndrome is a rare condition of muscular pseudohypertrophy and long standing moderate to severe … in children
A
  • Kocher Debre Semelaigne syndrome is a rare condition of muscular pseudohypertrophy and long standing moderate to severe hypothyroidism in children

Year 2 Medicine (162 decks)

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