Mineral Metabolic Disorders Flashcards
(160 cards)
1
Q
Congenital metabolic disorders that result from ?
A
absence or abnormality of an enzyme or its cofactor, leading to either:
1. accumulation
2. deficiency of a specific metabolite
2
Q
most congenital metabolic disorders are inherited how?
A
autosomal recessive
Fabry’s which is X-chromosome disorder
3
Q
how to diagnose cogenital metabolic disorders
A
enzyme essays
genetic testing
4
Q
what metabolism plays a vital role in cellular function by providing the energy required for most metabolic processes
A
Carbohydrate Metabolism
5
Q
the byproduct of sucrose/sorbitol
A
high fructose corn syrup
6
Q
function of glycogen
A
- long term storage of energy
- Formed during periods of dietary carbohydrate loading
- Broken down when glucose demand is high or dietary availability is low
7
Q
where is glycogen stored?
A
cells of liver and muscles
8
Q
muscle glycogen is converted to glucose during periods of ?
A
high energy muscle activity
9
Q
liver glycogen is converted into glucose when?
A
for energy throughout the body and CNS
- maintenance of glucose homeostasis while fasting
10
Q
genetic inheritance of glycogen storage diseases
A
MC autosomal recessive
some X-linked
10
Q
what 2 organ systems affected during glycogen storage disease will determine clinical presentation
A
liver
muscles
11
Q
Glucose is stored in tissues as
A
glycogen
11
Q
GSD affecting liver will present how?
A
- fasting hypoglycemia and ketosis
- sx improve with eating or glucose administration - (+/-) hepatomegaly
11
Q
GSD affecting the muscles will present how?
A
- muscle cramps, exercise intolerance and easy fatigability, progressive weakness
- variable cardiac involvement with cardiomyopathy and conduction defects
- Delayed growth in children but are usually developmentally normal
11
Q
diagnosing glycogen storage disease
A
hypoglycemia
elevated LFT’s
CPK
genetic testing
11
Q
management of glycogen storage disease
A
- Avoidance of hypoglycemia
- Enzyme replacement therapy may be available for some subtypes
- sx therapy
11
Q
3 subtypes of Fructosemia
A
- Deficiency of fructose 1,6-diphosphatase (FDPase) (aka fructose 1,6-bisphosphatase)
- Deficiency of fructose 1,6-bisphosphate aldolase - aka aldolase B (Hereditary Fructose Intolerance)
- Deficiency of fructokinase (Essential Fructosuria)
11
Q
deficiency of FDPase results in ?
A
inadequate glucose production during periods of fasting (between meals and during sleep)
11
Q
management for fructosemia (Fructose 1,6-bisphosphatase Deficiency)
A
avoid fructose and prolonged fasting
11
Q
An autosomal recessive condition resulting in an inability to metabolize fructose properly
A
Fructosemia
11
Q
what happens in hereditary fructose intolerance
A
Inadequate breakdown of fructose causing a toxic accumulation of fructose-1-phosphate in the liver, kidney and small intestine, leading to cell death
11
Q
how to diagnose hereditary fructose intolerance
A
genetic testing
11
Q
management of hereditary fructose intolerance
A
complete avoidance of fructose and sucrose
11
Q
pathophys of Essential fructosuria
A
Incomplete metabolism of fructose in the liver leading to its excretion in urine
Often found incidentally as glucose in the urine
11
A benign (asx) condition resulting from a lack of fructokinase
Essential fructosuria
no management needed
11
Autosomal recessive defect of chromosome 9p13
lack of metabolism of galactose = toxic accumulation of galactose-related molecules
Galactosemia
11
sources of galactose
1. Human/cow milk
- lactose = glucose + galactose
2. Baby formula
3. Some fruits/vegetables
- celery, kiwi, plum, avocado, figs
11
presentation of Fructose 1,6-bisphosphatase Deficiency
1. Related to hypoglycemia
- hunger, irritability, lightheadedness, fatigue, and lethargy, seizures, loss of consciousness, trembling, and sympathetic signs such as tachycardia, hypertension, or miosis
2. Related to acidosis (due to lactate build up)
- hyperventilation, nausea, vomiting and lethargy
11
3 types of enzyme deficiencies with Galactosemia
1. Galactose-1-phosphate uridyl transferase (GALT) deficiency (type 1- Classic galactosemia) - MC
2. Galactokinase deficiency (GALK)(type 2)
3. Galactose epimerase deficiency (GALE)(type 3)
11
presentation of Classic Galactosemia - Type 1
1. Normal at birth
2. Within few days: decreased appetite, V/D, failure to thrive, hepatomegaly and jaundice
3. complications:
- sepsis, intellectual deficits, movement disorders, ovarian failure (females), liver/kidney failure
- cataracts form with in 2 wks due to galactitol deposition
11
which GALK deficiency is known to primarily present with cataract formation
Type 2
11
which Galactosemia deficiency is known to primarily present with cataract formation
Type 2
11
which Galactosemia deficiency is known to present ranges from asx to “classic presentation”
GALE deficiency - Type 3
11
which Galactosemia deficiency is known to primarily present with cataract formation
GALK deficiency - Type 2
11
labs for Galactosemia
1. GALT enzyme deficiency included in newborn screening (WV)
2. RBC galactose-1-phosphate - elevated in GALT deficiency
3. GALT enzyme activity - reduced in GALT deficiency
11
management for Galactosemia
Minimize dietary galactose
1. d/c breastfeeding or traditional formula
2. Use soy-based formulas (ie. Alsoy, Isomil, ProSobee)
3. Later avoid dairy products; lactose-free considered safe later on
11
what mainly function as building blocks for proteins and synthesis of hormones and neurotransmitters
Amino acids (AA)
11
AAs that are endogenously made
Non-essential
1. alanine
2. arginine
3. asparaginee
4. aspartic acid
5. cysteine
6. glutamic acid
7. glutamine
8. glycine
9. proline
10. serine
11. tyrosine
11
health maintenance for galactosemia
1. Yearly nutrition consult and ophthalmology exams
2. Monitor CBC, LFT, RBC galactose-1-phosphate levels
3. Monitor LH, FSH, estradiol in females starting at age 10
11
AAs that must be obtained through the diet
essential AAs
1. histidine
2. isoleucine
3. leycine
4. lysine
5. methionine
6. phenylalanine
7. threonine
8. tryptophan
9. valine
11
3 products of Carbohydrate Metabolism
1. Glucose
- primary source of energy from ingestion of polysaccharides (primarily starch) and disaccharides (lactose, maltose, and sucrose)
2. Galactose
- lactose derivative (broken down to galactose + glucose)
- found in milk products
3. Fructose
- fruits, vegetables, and honey
11
how do AA metabolism disorders happen?
AA unable to catabolize = accumulation of the AA compound in the blood or urine
All are screened for in newborn screening (WV)
11
Autosomal recessive mutation of chromosome 12
A deficiency of an enzyme called phenylalanine hydroxylase (PAH)
Phenylketonuria (PKU)
11
what converts phenylalanine → tyrosine
phenylalanine hydroxylase (PAH)
11
deficiency of phenylalanine hydroxylase (PAH) leads to what?
toxic accumulation of phenylalanine in the brain
11
Defects in glycogen metabolism results in ?
accumulation of glycogen in the tissues
11
presentation of Hereditary Fructose Intolerance
1. Infant - initially healthy and sx
2. sx begin when fructose/sucrose ingested
- usually from fruit, sweetened cereal, or sucrose-containing formula
3. Clinical manifestations
- severe abd pain, vomiting
- failure-to-thrive
- jaundice, hepatomegaly
- sx of hypoglycemia - lethargy/irritability/convulsions
Complications: liver and renal failure
12
Phenylalanine excess results in ?
destruction of the myelin (fatty covering)of individual nerve fibers
13
Phenylketonuria (PKU) is MC in who?
Caucasians and Native American’s
Rare - African, Hispanic, or Asian ancestries
14
presentation + complications of PKU
1. normal at birth
2. With in a few days: loss of appetite, weakness, vomiting, irritability
Complications/left untx:
1. Unusually light hair and skin (phenylalanine interferes with melanin production)
2. Neuro dysfunction: (loss of myelin)
- Moderate to severe intellectual disability
- Epilepsy
- Abnormal gait/posture/stance
- Problems with executive functioning
15
diagnosing PKU
Newborn screen (all 50 states)
Elevated levels of plasma phenylalanine
16
management for PKU
1. Dietary restriction of phenylalanine
- Meats, dairy, nuts
- Aspartame
2. Two FDA approved drugs that reduce blood phenylalanine concentrations
- sapropterin (Kuvan)
- pegvaliase (Palynziq)
17
which med
adults/peds
activates PAH to promote the breakdown of phenylalanine
sapropterin (Kuvan)
18
which med
adults only - degrades phenylalanine
pegvaliase (Palynziq)
19
Autosomal recessive disorder
Deficiency in the enzyme complex (branched-chain ketoacid dehydrogenase complex - [BCKDC]) required to break down branch-chain amino acids (BCAA)
Maple Syrup Urine Disease
leads to an accumulation of these BCAA and their byproducts throughout the body
20
3 BCAA affected in maple syrup urine disease
leucine
isoleucine
valine
21
Accumulation of leucine causes
neurological symptoms
22
what causes maple syrup odor in maple syrup urine disease
Elevation of plasma isoleucine
Urine has a sweet odor, much like burnt caramel
23
source of BCAA for MSUD
eggs, soy protein, white fish, pork, beef, tofu, parmesan, sesame
24
presentation of classic MSUD
1. <3% residual enzyme activity
2. sx begins within 48 hours - 2 weeks (breastfeeding delays onset)
- irritability, poor feeding, vomiting, lethargy, dystonia → apnea, seizures, cerebral edema → death if unrecognized
MC form
25
presentation of non-classic MSUD
1. 3-30% enzyme activity
2. onset may be later (infancy-childhood)
- exacerbated by physical stress
3. variable sx severity (as in classic MSUD)
- epigastric pain, vomiting, anorexia, and muscle fatigue
- hyperactivity, sleep disturbance, stupor, decreased cognitive function, dystonia, and ataxia
26
presentation of non-classic MSUD
1. 3-30% enzyme activity
2. onset may be later (infancy-childhood)
- exacerbated by physical stress
3. variable sx severity (as in classic MSUD)
- epigastric pain, vomiting, anorexia, and muscle fatigue
- hyperactivity, sleep disturbance, stupor, decreased cognitive function, dystonia, and ataxia
27
diagnosing MSUD
Newborn screening (all 50 states)
Prenatal screening¹ is available
28
management for MSUD
1. Dietary management: strict protein restriction
- medical grade formula/food
- constant balancing act between giving enough food, protein and BCAAs to allow for normal growth without toxic accumulation
2. Trial of thiamine supplement for 4 weeks
- some subtypes respond to thiamine
3. Control of metabolic decompensation
- Rapidly lower leucine levels - hemodialysis
- Inhibition further protein catabolism and enhance protein synthesis
--- D/c protein intake x 24-48 hrs
--- IV glucose - provides calories (prevents protein catabolism for energy)
--- IV insulin if glucose is > 130 mg/dL
4. Liver transplant
- Appx 10% of BCKDC enzyme is expressed in the liver
- Last resort in classic MSUD
29
what hormone enhances endogenous protein synthesis
insulin
30
Dysfunction of the metabolism of the amino acid methionine resulting in an accumulation of homocysteine and its metabolites
Homocystinuria
31
Homocystinuria Results from a deficiency in several enzymes but MC what?
cystathionine β-synthase
32
presentation of Homocystinuria
1. Failure to thrive
2. Dislocated optic lenses and mental retardation
- MC
- between 3-5 y/o
3. Marfanoid habitus
4. Musculoskeletal deformity with osteoporosis
- Pes excavatum (sternum sinks in)
- Pes carinatum (protrusion of sternum)
- Genu valgum (knock knees)
5. Thromboembolic related sx
- hemiplegia, aphasia, ataxia, pseudobulbar palsy
33
diagnosing Homocystinuria
Newborn screening (WV)
Elevated levels of homocysteine and methionine in the plasma or urine
34
management for Homocystinuria
1. Diet modification - protein restriction
2. Vitamin B6, B12, folate supplements: helps convert homocysteine to methionine
3. Betaine (Cystadane): helps convert homocysteine to methionine
35
what organelle enables the cell to process its nutrients and are also responsible for destroying the cell after it has died
lysosome
Formed in the cell by the Golgi body
36
what protects the lysosome protects the cell from inappropriate destruction
membrane
37
function of lysosome
1. Release enzymes outside of the cell (exocytosis)
- serves to destroy materials around the cell
2. Digests unwanted materials from inside and outside the cell
3. Completely break-down cells that have died (autolysis)
4. Digests proteins, nucleic acids, carbohydrates, and lipids for use by the cell
5. Cell membrane repair
38
Disorders that results from an abnormality in the biosynthesis of the lysosome which results in impaired enzyme activation
Lysosomal Storage Disorders
39
Disorders that results from an abnormality in the biosynthesis of the lysosome which results in impaired enzyme activation
Lysosomal Storage Disorders
40
classifications of Lysosomal Storage Disorders
1. Tay-Sachs disease
2. Gaucher’s disease
3. Fabry disease
4. Niemann-Pick disease
5. Pompe disease
Classified according to the nature of the stored material
41
An autosomal recessive, neurodegenerative disorder resulting from a mutation of the lysosomal enzyme, hexosaminidase A (Hex A)
Tay-Sachs Disease
42
what helps to break down a fatty substance called GM2 ganglioside
hexosaminidase A
43
buildup of GM2 ganglioside results in ?
destruction of neurons in the brain and spinal cord
44
3 subtypes of Tay-Sachs Disease
1. infantile
2. juvenile
3. adult onset
varies based upon amount of enzyme present
45
Clinical Presentation: Infantile Tay-Sachs Disease
1. Normal until 3-6 m of age
2. First clue: exaggerated startle (Moro) reflex (normally disappears 3-6 m)
3. First sx - slowing of normal milestone development
- Gross muscle weakness - inability to turn over, sit or crawl
4. Progression of disease results in seizures, vision and hearing loss, intellectual disability, and paralysis
5. Cherry-red spot on fundoscopy (hallmark)
- accumulation of GM2 ganglioside in retinal ganglion cells
46
life expectancy of infantile Tay-Sachs Disease
2-5 yrs
death often from complications of pneumonia
47
Clinical Presentation of juvenile Tay-Sachs disease
1. sx onset between 2-5 y/o
2. Frequent rsp infections, behavioral problems, slow loss of motor control and mental function
3. Progresses to unresponsiveness/unawareness for yr before death
48
life expectancy for juvenile tay-sachs disease
Death by age 10–15 years - most often infectious related
49
presentation of adult tay-sachs disease
often difficult to diagnosis
1. Clumsiness in childhood
2. Progressive motor weakness in adolescence
3. Dysarthria in adulthood
4. Intelligence declines slowly
5. 40% experience mental health issues
6. Effect on lifespan varies
50
diagnosing tay sachs disease
1. Genetic testing/counseling
- Screening during pregnancy possible
2. Hex A/B enzyme analysis²
- Tay-Sachs - low Hex A; normal or high Hex B
51
management for tay-sachs disease
Supportive care
- sx control - pain, seizures
- Manage infections
- Prevent complications - physical and occupational therapy, feeding tube
**No effective treatment**
52
prevention of tay sachs disease
Carrier screening and genetic counseling is vital
- Descendants from: Ashkenazi Jews, French-Canadians, Cajuns
- (+) family history
53
Autosomal recessive mutation on chromosome 1
Results from a deficiency in glucocerebrosidase (GCase)
Gaucher Disease
54
a component of cell membranes, that are released when cells are degraded
breaks down glucocerebroside into glucose and ceramide
glucocerebrosidase (Gcase)
55
Excessive glucocerebroside builds up in macrophages known as ____ that build up in the ___, which causes ___
Gaucher cells
spleen, liver, bone marrow (and brain in severe cases)
chronic inflammation and fibrosis
56
Gaucher Disease is MC in who?
Ashkenazi Jewish ancestry with a 1:12 carrier state
57
3 subtypes of Gaucher Disease
1. G1 - MC
- Bone marrow fibrosis, osteopenia, HSM,
- No CNS involvement
- Slow progression - often dx before age 20
- Normal life span
2. G2 and G3
- Earlier onset, more aggressive, shorter life span
--- G2 - death usually by age 2
--- G3 - slower rate of neurologic sx
- Seizures, ataxia, hypotonia, MR, dementia
58
all types of Gaucher disease can cause what?
“Bone crises”
1. Localized excruciating pain, local erythema, fever, and leukocytosis.
- Gaucher cells infiltrate BM = infarction, ischemia, necrosis, and cortical bone destruction
59
diagnosing Gaucher disease
1. Newborn screening - only in Missouri, New Jersey, Illinois Tennessee
2. Low beta-glucosidase leukocyte enzyme activity (Hallmark)
3. Genetic testing
- only way to determine carrier state
--- Recommended: Ashkenazi Jewish
- prenatal testing is possible
60
management for Gaucher Disease
1. Enzyme-replacement therapy (ERT) with recombinant glucocerebrosidase (Imiglucerase)
- not effective in reducing or reversing CNS sx
2. Substrate-reduction therapy (SRT)
- blocks the production of glucocerebroside (fatty substance)
- eliglustat (Cerdelga), miglustat (Zavesca)
61
A deficiency of alpha galactosidase A (GLA) leading to an accumulation of globotriaosylceramide¹ (GL3), a fatty substance in the blood vessels
Fabry Disease
62
with Fabry disease, GL3 builds up in the blood and blood vessel wall resulting in
narrowed blood vessels which leads to inadequate oxygen
63
Fabry disease is MC affects what systems
skin, kidneys, heart, CNS
63
Fabry disease is MC affects what systems
skin, kidneys, heart, CNS
64
genetic inheritance of Fabry Disease
X-linked inheritance
Males more severely affected than females
65
presentation of Fabry Disease
1. asx - severe
2. Angiokeratomas
3. Hypo- or anhidrosis
4. Corneal and lens opacities - deposits of glycolipids in the corneas
5. Acroparesthesia - severe episodic (lasting min-days) burning pain of the extremities
- precipitated by temperature, exercise, fatigue, or fever
6. Progressive, small-vessel disease of the kidney, heart, and brain ultimately results in death
66
punctate, dark red to blue-black, flat or slightly raised lesions, and usually symmetric
do not blanch with pressure
most abundant between the umbilicus and the knees—the “bathing suit area”
Angiokeratomas
67
diagnosing Fabry Disease
GLA enzyme activity - decreased
Confirmed with genetic testing
68
management of fabry disease
1. Enzyme-replacement - first line
- agalsidase beta (Fabrazyme)
2. Chaperone therapy: migalastat (Galafold)
- MOA: increases GLA enzyme activity preventing accumulation of GL3
- Adults only
3. sx control and complication prevention
- Control neuropathic pain
- Stroke prevention - ASA plus clopidogrel, antihypertensives, statins
69
An autosomal recessive disorders resulting in a deficiency of acid sphingomyelinase (ASM) leading to an accumulation of sphingomyelin¹ within macrophages and other cells, eventually causing cell death and organ malfunction
Niemann-pick Disease (NPD)
70
Niemann-pick Disease (NPD) MC affects what organs
spleen, liver, lungs, bone marrow, and brain
71
what are “foam” cells
macrophages of NPD and looks like soap-suds
72
3 subtypes of Niemann-pick Disease
NPA
NPB
NPC
73
which NPD
1. Onset within 6 months after birth
2. Rapidly progressive CNS deterioration, spasticity, failure to thrive, interstitial lung disease and massive HSM
3. Death usually occurs within 2 years
NP-A
74
which NPD
1. Onset: late childhood/adolescent
2. Progressive HSM, cirrhosis (“foam” cells replace liver cells, )
3. “Foam” cells are found in alveoli and pulmonary arteries
- ILD: dyspnea, hypoxemia, reticular infiltrative pattern on chest x-ray
4. Death in adolescence or early adulthood from liver/lung failure
NP-B
75
which NPD
1. Onset: middle-late childhood after normal early development
2. Liver, spleen, and/or lung involvement is present in ≥85% of pts + neurologic disease
- Start out clumsy → progression to ataxia, dysphagia, dystonia, seizures
3. Death usually secondary to aspiration pneumonia
NP-C
76
dianogisng NPD
Newborn screening (not in WV)
Genetic testing
77
management for NPD
1. Supportive care only
- Physical and occupational therapy
- Feeding tube for nutrition if needed
- Oxygen therapy as needed
- Blood transfusion as needed
- Avoid contact sports if splenomegaly
2. Monitor growth, platelets, liver enzymes, fasting lipids, pulmonary function tests, CXR, and bone density scans
78
Autosomal recessive mutation on chromosome 17
Results from a deficiency in acid αlfa-glucosidase (GAA) resulting in an inability to break glycogen into glucose for energy
also classified as a glycogen storage disease
Pompe Disease
79
in Pompe disease, Glycogen accumulates within the lysosome in all tissues, leading to ?
a lysosomal-mediated degradation of glycogenesis and tissue destruction
80
3 subtypes of Pompe Disease
1. Classic infantile-onset - onset within a few months of birth
- hypotonia, myocardiopathy, HSM
- rapidly progressive, generally results in death before age 1 year
2. Non-classic infantile-onset - onset by 12 months after birth
- delayed motor skills (rolling over, sitting)
- progressive muscle weakness leads to rsp dysfunction
- cardiomegaly without HF
- results in death by early childhood
3. Late-onset
- onset late childhood, adolescence, or adulthood
- milder than other forms of disease, less likely to involve the heart
- slowly progressive muscle weakness
--- legs, trunk, rsp muscles
- leads to rsp failure at an older age
81
diagnosing Pompe disease
1. Newborn screening (not in WV)
2. Acid alpha-glucosidase (GAA) enzyme levels - decreased
3. Genetic testing confirms dx
4. Prenatal diagnosis via DNA analysis, amniocentesis, or CV sampling
82
management of Pompe Disease
1. Enzyme replacement therapy - alglucosidase alfa (Lumizyme)
- Antibody formation to ERT is problematic
2. Monitoring: continued risk of gradual weakness, fractures, dysphagia, and sleep apnea despite treatment
83
Phosphate absorption/excretion
1. absorbed from ingested food in the small intestines
- requires presence of vitamin D
2. excreted by the kidneys
- requires PTH
84
Phosphate absorption/excretion
1. absorbed from ingested food in the small intestines
- requires presence of vitamin D
2. excreted by the kidneys
- requires PTH
85
Phosphate function
bone and teeth formation
building block for cell for energy, cell membranes, and DNA
86
Phosphate storage
85% stored in mineral phase of bone
15% stored in intra- and extracellular compartments
87
Phosphate storage
85% stored in mineral phase of bone
15% stored in intra- and extracellular compartments
88
3 causes of Hyperphosphatemia
1. Increased phosphate intake
- uncommon if kidney function is intact
2. Decreased phosphate excretion
- MC - CKD
- Acute kidney dysfunction
- Hypoparathyroidism
- Vit D intoxication
- Genetic syndromes of tumoral calcinosis
3. Shift of intracellular phosphate to extracellular space
- rhabdomyolysis and tumor lysis exacerbates hyperphosphatemia in disorders of kidney dysfunction
89
presentation of Hyperphosphatemia
symptoms related to underlying condition or hypocalcemia
90
management for Hyperphosphatemia
1. acute severe disease
- IV fluids if no CKD
- hemodialysis if CKD
2. tx is directed to underlying condition
3. mild disease- dietary restrictions
- avoid dairy items, meats, and beans
4. moderate/severe - phosphate binders
- calcium acetate (PhosLo)
- lanthanum carbonate (Fosrenol)
- sevelamer (Renagel)
91
what med
Chelates phosphate in intestine to form insoluble calcium phosphate, which is excreted in feces
Calcium acetate
92
what med is indicated for Hyperphosphatemia in End Stage Renal Failure (ESRD)- On Dialysis
Calcium acetate
93
SE of Calcium acetate
hypercalcemia, diarrhea, hypophosphatemia, hypotension, arrhythmias, nausea, vomiting
pregnancy - compare risk/benefit - should not cause problems as long as calcium levels are monitored
94
DI of Calcium acetate
avoid with digitalis use - increases toxicity of digitalis
95
what med is indicated for Hyperphosphatemia in ESRD
Fosrenol (lanthanum carbonate)
96
what med
binds with phosphate inhibiting GI absorption
Fosrenol (lanthanum carbonate)
97
SE of Fosrenol (lanthanum carbonate)
GI - N/V/D/C, abd pain, HA
Pregnancy - not preferred during pregnancy
98
what med is indicated for Hyperphosphatemia in ESRD On dialysis
Renagel (sevelamer)
99
what med
Polymeric phosphate binder - decreases serum phosphate concentrations without changing calcium, aluminum, or bicarbonate concentrations
Renagel (sevelamer)
100
SE of Renagel (sevelamer)
1. GI - N/V/D/C, dyspepsia, arthralgias/limb pain, metabolic acidosis
2. Pregnancy
- may reduce maternal absorption of fat soluble vitamins and folic acid
- expected to be safe due to lack of systemic absorption
101
3 causes of Hypophosphatemia
1. Inadequate intake
2. Increased excretion
3. Shift from extracellular to intracellular space
102
cause of inadequate intake of hypophosphatemia
1. Intestinal malnutrition
2. Vitamin D deficiency
3. Excessive use of antacids (calcium-, magnesium-, or aluminum-containing)
- bind phosphate in the gut and prevent the body from absorbing it
Inadequate intake alone usually isn’t enough to lead to low levels as phosphorus is abundant in most foods and easily absorbed
103
cause of increased excretion of hypophospatemia
1. MC - hyperparathyroidism
2. Forced saline diuresis
3. Genetic disorders resulting in phosphate wasting
- Fanconi Syndrome
104
cause of Shift from extracellular to intracellular space to cause hypophosphatemia
1. Uncommon etiology
2. Results as an exacerbation produced by other mechanisms
- diabetic ketoacidosis, refeeding syndrome¹
--- both result from insulin shifting phosphate into the cell
- short-term increases in cellular demand (eg, hungry bones syndrome) and acute respiratory alkalosis
105
presentation of Hypophosphatemia
1. mild - often asx (2-2.5 mg/dL)
2. severe - (< 2 mg/dL)
- weakness, bone pain, muscle pain, rhabdomyolysis
- evidence of heart failure
- focal neurologic findings, seizures, altered mental status
106
management for Hypophosphatemia
1. Treat underlying disorder if known
2. Mild hypophosphatemia
- Increase dietary phosphate intake - dairy items, meats, and beans
3. Moderate-severe hypophosphatemia
- phosphate supplement - sodium or potassium phosphate
107
Phosphorus supplements are available in what form
sodium phosphate or potassium phosphate in capsule or liquid form
108
SE of Phosphorus supplement
weakness, N/V/D, abdominal pain, bradycardia, arrythmia
safe in pregnancy
109
CI of Phosphorus supplement
Hyperphosphatemia, severe renal impairment, hyperkalemia
110
function of magnesium
energy transfer, storage, and use
protein, carbohydrate, and fat metabolism
maintenance of normal cell membrane function
assistance in PTH regulation
111
storage of magnesium
1. 99% is intracellular or bone-deposited
- 60% - bone
- 20% - muscle
- 20% - soft tissue, liver
2. 1% in extracellular space
112
food sources with magnesium
green vegetables, cereals, grains, nuts, legumes, and chocolate
113
causes of hypomagnesemia
1. Decreased intake
- alcohol abuse, prolonged parenteral nutrition, extremely poor diet
2. Redistribution of magnesium from the extracellular to the intracellular space
- “hungry bone syndrome”
3. Increased renal or GI loss
- malabsorption of small intestines, vomiting, diarrhea
- renal disorders resulting in magnesium wasting
114
presentation of hypomagnesemia
1. associated with hypokalemia and hypocalcemia
2. Presentation is often related to CV system, CNS and PNS
- cardiac arrhythmias
- muscular weakness, tremors, seizure, paresthesias, nystagmus
- Chvostek and Trousseau signs, carpopedal spasms progressing to tetany (with hypocalcemia)
115
management of hypomagnesemia
1. Increase dietary magnesium
- Dark green vegetables, legumes (beans and peas), nuts and seeds, and whole, unrefined grains
2. pharm
- Severely sx (tetany, arrhythmia) - IV Magnesium
- Mild-moderate - oral magnesium
3. Replenish calcium and potassium if indicated
116
A disorder of unknown etiology resulting in bone remodeling that typically begins with excessive bone resorption followed by an increase in bone formation
Paget Disease
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what are the 2 cellular bone maintenance
1. osteoclast “crusher”- a large multinucleate bone cell that absorbs bone tissue during growth and healing
2. osteoblast “builder”- a cell that secretes the matrix for bone formation
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pathophys of Paget Disease
1. overactive osteoclasts results in compensatory osteoblastic activity
= structurally disorganized mosaic of bone that is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture
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Paget Disease is MC found where in the body?
1. axial skeleton
2. spine, pelvis, femur, sacrum, and skull
Most often affects more than one bone but doesn’t spread from one bone to the other
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presentation of paget disease
1. asx - MC
2. Bone pain - MC
- dull, deep, aching, worse at night
3. Secondary osteoarthritis - if activity near joint
4. Bony deformity
- bowing of an extremity
5. Excessive warmth (due to hypervascularity)
6. Neurologic complications (caused by the compression of neural tissues)
- MC hearing loss
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work-up for paget disease
1. Elevated alkaline phosphatase and bone specific alkaline phosphatase (BSAP)
- increased with osteoblast activity
2. X-ray
- Early disease - lytic lesions (bone destruction)
- Later in disease - lytic lesions and excessive bone formation
3. Radionucleotide bone scan
- determines the extent of the disease
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complications with paget disease
Fractures, bone neoplasms, neuromuscular syndromes, joint disease
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management/tx for paget disease
1. bisphosphonate - prevent osteoclast activity
- alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), zoledronic acid (Reclast)
2. NSAIDs for joint pain
3. Calcium and Vit D supplementation
