Metabolic disorders Flashcards
Mild and asymptomatic (majority)
Bone pain aching, deep and worse at night initially
MCC: pelvis, vertebrae, femur, humerus, skull
Softening of bones → long bones proximally and advancing distally with bowed tibias, kyphosis, “chalk stick” fractures
Skull enlargement = headaches, increased hat size, damage to petrous temporal bone → cochlea → hearing loss, tinnitus, vertigo
paget disease
RF for paget disease
UK, Europe
>55
Genetic - autosomal dominant w/ incomplete penetrance
Precise cause unknown, maybe viral infection (measles) in bone cells
Associated with osteosarcoma
paget’s disease
PE: dilated scalp veins “scalp vein sign”, crepitus of the hip
LABS: elevated serum ALP, serum N-terminal propeptide of type 1 collagen, serum beta C-terminal propeptide of type 1 collagen
Elevated calcium (nonambulatory)
Serum 25-OH vitamin D
IMAGING:
initial lesions = osteolytic
Advanced = flame-shaped lytic lesions in long bones
– become sclerotic and have mixed lytic/sclerotic appearance with thickened and deformed bones
Technetium-99m pyrophosphate bone scan: find additional lesions
→ baseline should be obtained in all patients to document extent and locations
paget’s disease
XR = diagnostic with demonstration of characteristic changes at 1+ sites
“Cotton wool” appearance
paget’s disease
How do you treat paget’s disease?
Asymptomatic = clinical surveillance
Skull, long bones, or vertebrae involvement = bisphosphonates
Zoledronic acid IV
Calcium and vitamin D supplements
→ correct Vitamin D deficiency prior to treatment
High iron levels w/ no symptoms or:
Early: fatigue or arthralgia
Later: joint disease-symmetric arthropathy, hepatomegaly (cirrhosis), skin pigmentation (gray/brown), cardiac enlargement, DM (late-onset Type 1), erectile/gonadal dysfunction
Classic triad: cirrhosis, bronze skin, DM1
hemochromatosis
Autosomal recessive gene
>50 men
Worse w/ EtOH use, obesity, DM
RF for hemochromatosis
Iron overload and deposition disorder
Hemosiderosis = accumulation in tissue (liver, pancreas, heart, adrenals, testes, pituitary, kidneys)
High incidence of hepatocellular carcinoma + intrahepatic cholangiocarcinoma
hemochromatosis
Elevated plasma iron w/ transferrin sat > 45%, increased ferritin, iron
Low unsaturated iron binding capacity-UIBC
Mildly elevated AST and alk phosphatase
MRI/CT – show iron overload in liver
Liver biopsy
Ass w/ alpha fetoprotein (cancer)
hemochromatosis
Check for iron overload in patients w/:
-Chronic liver disease
-ED
-Chondrocalcinosis
-DM1, late onset
Consider genetic testing, liver biopsy, MRI if screening tests are high
hemochromatosis
How do you treat hemochromatosis?
Avoid intake - red meat, supplemental iron, etc
ETOH, Vitamin C, raw shellfish
Depletion of iron stores by phlebotomy - 2-3y of weekly phlebotomy
Done for symptomatic patients
OR men-serum ferritin OR high fasting iron saturation
Consider PPIs to lower maintenance phlebotomy need
Chelation w/ deferoxamine if pt has anemia w/ iron overload from Thalassemia and intolerant of phlebotomy
Adolescents = presents as liver disease
Young adults = presents as neuropsychiatric disease
Should be considered in any child or young adult with:
hepatitis, splenomegaly with hypersplenism, Coombs negative hemolytic anemia, portal HTN, neurologic or psychiatric abnormalities
anyone <40 with chronic hepatitis or acute liver failure
wilson’s disease
What are RFs for Wilson disease
3-55
Adolescent females
Young adult males
Autosomal recessive disorder - genetic defect on chromosome 13 (ATP7B)
MC: H1069Q variant
Excessive absorption of copper from small intestine + decreased excretion of copper by the liver → increased tissue deposition in liver, brain, cornea, kidney
Wilson disease
LABS: elevated liver enzymes, cirrhosis, portal HTN
Neuro signs = akinetic-rigid syndrome, pseudosclerosis with tremor, ataxia, dystonic syndrome, dysarthria, dysphagia, incoordination, spasticity, migraines, insomnia, seizure
Psych = behavioral/psychiatric changes, emotional lability, depression
Brown or gray-green Kayser-Fleischer ring
Wilson disease
DIAGNOSIS:
Increased urinary copper excretion (>40)
Low serum ceruloplasmin levels (<14)
Elevated hepatic copper concentration (>250)
Kayser-Fleischer rings
Liver biopsy
MRI of brain
wilson disease
How do you treat wilson disease
Restriction of dietary copper (shellfish, organ, nuts, mushrooms, chocolate)
Oral D-penicillamine - 1 hour before or 2 hours after food
Oral pyridoxine to refresh B6 stores
SE: GI intolerance, hypersensitivity, autoimmune reactions, nephrotoxicity, bone marrow toxicity
Trientine hydrochloride (less SE, but $) or trientine tetrahydrochloride
2nd line = oral zinc acetate or zinc gluconate for first line asymptomatic or pregnant patients, maintenance
normal BMI
18.5-24.9
overweight BMI
25-29.9
class 1 obesity
30-34.9
class 2 obesity
35-39.9
Class 3 obesity:
40+
What are RFs for obesity
Americans
Type 2 diabetes
HTN
HLD
Heart disease
Stroke
OSA
Accumulation of visceral subcutaneous fat
Central obesity is a greater health risk than lower body
Can be from drugs, medications (steroids, contraceptives, anti-diabetics,anti-HTN, antidepressants, antipsychotics, antiepileptics, antihistamines), alcohol use
Genetic: 40-90%
Environmental
Behavior
obesity
Serum albumin is the most important test to identify whether someone is protein malnourished
History: age, changes, family history, occupation, eating/exercise behavior, WL experience, psychosocial factors (ED)
Physical: BMI, distribution, overall status, secondary
Screen all for weight-related comorbid conditions, including OSA
BP, waist circumference, fasting glucose, CMP, lipid panel, HgbA1c
obesity
What are recommendations for exercise in obesity?
150 minutes of moderate intensity aerobic exercise/week (tennis, walking)
75 minutes of vigorous intensity aerobic exercise per week (jogging, swimming)
Resistance training
non-pharm obesity treatment
diet, physical activity, behavior modifications
→ unprocessed foods, limiting high calorie foods, emphasizing mediterranean diet, low-glycemic index diet, meal replacement
→ meal planning, self-monitoring, food log, recognize eating cues
→ aerobic exercise, higher intensity
pharm treatment of obesity
in those with BMI 30+ or BMI 27+ with comorbidities (DM) with diet and exercise
– phentermine (short term use, adrenergic agonist), orlistat (GI SE), phentermine/topiramate ER (longer term, not for pregnancy), naltrexone/bupropion SR (suicidality in <24 years), liraglutide, semaglutide (AGA endorses this over others but can increase risk of thyroid cancer), tirzepatide
Bariatric surgery in those with BMI
40+ or 35+ with complications (sleeve gastrectomy - irreversible, Roux-en-Y gastric bypass - reversible)
– CI: poor cardiac reserve, COPD or respiratory dysfunction, severe psych disorders, nonadherence to medical treatment
Early = anorexia, muscle cramps, paresthesia, irritability
Advanced =
-Wet beriberi - CV: (peripheral vasodilation with high-output heart failure with dyspnea, tachycardia, cardiomegaly, pulmonary edema, peripheral edema with warm extremities)
- Dry beriberi - peripheral nervous involvement (symmetric motor/sensory neuropathy with pain, paresthesia, areflexia)
CNS - Wernicke-Korsakoff syndrome (Wernicke encephalopathy, Korsakoff dementia)
vitamin B1 deficiency
(thiamine) - MCC: alcohol use disorder, malabsorption, dialysis, other causes of chronic protein-calorie undernutrition
Active = pyrophosphate
Absorbed in small intestine
B1 deficiency
thiamine
B1
riboflavin
B2
Dx: clinical response to empiric thiamine therapy
Biochemical test – normal 70-180
Erythrocyte transketolase activity (subclinical = low)
Urinary thiamine excretion (recent intake)
No known toxicity
B1 deficiency
how do you treat b1 deficiency
Large parenteral doses of thiamine (only effective if magnesium is repleted)
– should receive simultaneous therapeutic doses of other water-soluble vitamins
Dry beriberi → neuro
Wet beriberi → cardio
Cheilosis, angular stomatitis, glossitis – magenta-colored tongue
Seborrheic dermatitis
Weakness
Anemia
→ oral, ocular, genital syndrome
vitamin B2 deficiency
(riboflavin) - usually in combo with other deficiencies from dietary inadequacy, interactions with meds, alcohol use
No known toxicity
vitamin B2 deficiency
Erythrocyte glutathione reductase measurement – activity coefficients >1.2-1.4 are suggestive
Excretion to determine recent intake
vitamin b2 deficiency
how do you treat b2 deficiency
Treat empirically
Foods: meat, fish, dairy products
Oral preparations
IV preparations
Early = anorexia, weakness, irritability, mouth soreness, glossitis, stomatitis, weight loss
Advanced = triad of pellagra with dermatitis (dark, dry, scaly), dementia, diarrhea
b3 deficiency
(niacin) Alcohol use disorder, diet rich in corn, nutrient-drug interactions (isoniazid, fluorouracil, phenobarbital, pyrazinamide), Harnup disease
Major food sources = cereals, vegetables, dairy, proteins containing tryptophan
b3 deficiency
niacin
b3
Serum or plasma (normal = .50-8.45)
Toxicity can be caused by treating by hyperlipidemia – cutaneous flushing and gastric irritation - pre-treat with aspirin
Elevation of liver enzymes, hyperglycemia, and gout
b3 deficiency
Fat soluble vitamins
adek
how do you treat vitamin b3
Oral niacin as nicotinamide
Similar to other vitamin B deficiencies: mouth soreness, glossitis, cheilosis, weakness, irritability
Severe = peripheral neuropathy, anemia, seizures
vitamin b6 deficiency
pyridoxine
b6
(pyridoxine) alcoholism, medication interactions (isoniazid, oral contraceptives)
b6 deficiency
Blood: pyridoxal phosphate (normal = >5)
Toxicity with large doses (200-2000/day) causing irreversible sensory neuropathy
b6 deficiency
b6 deficiency
supplementation
Early = malaise/weakness
Advanced = scurvy symptoms (perifollicular hemorrhages, papules, petechiae, purpura, splinter hemorrhages), anemia, impaired wound healing
Late = edema, oliguria, neuropathy, hemorrhage, death
vitamin c deficiency
ascorbic acid
vitamin c deficiency
What are RF for vitamin C?
Chronic illness - cancer, CKD, smoking
(ascorbic acid) from dietary inadequacy and alcohol use disorder
3HS:
Hyperkeratosis
Hemorrhage (impaired wound healing, vascular fragility, gums)
Hematologic
vitamin c deficiency
Based on skin lesions
Atruamatic hemarthrosis = highly suggestive
Confirmed w/ plasma ascorbic acid levels <.2
Large doses can cause gastric irritation, flatulence, diarrhea, kidney stone
vitamin c deficiency
how do you treat vitamin c deficiency
ascorbic acid
Early = night blindness, corneal xerosis, bitot spots (white spots on conjunctiva)
Late = keratomalacia, endophthalmitis, blindness, xerosis of skin, hyperkeratinization, loss of taste
Dry eyes
common in developing countries
vitamin a deficiency
MCC of blindness
US = fat malabsorption syndromes or mineral laxative abuse
vitamin a deficiency
Dx: abnormalities of dark adaption are suggestive (clinically)
Serum levels <30-65
Large doses leads to staining of skin a yellow-orange color mostly on palms and soles with sclera remaining white
Excessive = toxic, with ingestion of daily doses over 50k/day for 3 months+
vitamin a deficiency
how do you treat vitamin a deficiency
Vitamin A daily for 1 week
Dry, scaly skin with hair loss, mouth sores, painful hyperostosis, anorexia, vomiting
More serious = hypercalcemia, increased intracranial pressure with papilledema, headaches, decreased cognition
Acute = N/V abdominal pain, headache, papilledema, lethargy
vitamin A toxicity
Hepatomegaly
Confirmed by elevations of serum vitamin A levels
vitamin A toxicity
how do you treat vitamin A toxicity
Withdrawal of vitamin A from diet
MSK pain or weakness, can lead to osteomalacia (soft bones) and secondary hyperparathyroidism
Diffuse pain and tenderness, proximal muscular weakness
Hip pain, bowing → waddling
vitamin d deficiency
what are RF for vitamin D deficiency
Community-dwelling older adults, residential care, increased skin melanin pigmentation, modestly dressed, not regularly exposed to sunlight, pregnant women, obesity
Low levels in blood → abnormalities in Ca, P, bone metabolism
Decreased synthesis in skin (dark, aging, lack of exposure), inadequate dietary intake, impaired GI absorption, nephrotic syndrome, anti seizure meds, rifampin, isoniazid, theophylline, steroids, impaired hepatic metabolism
vitamin d deficiency
25-hydroxyvitamin D <20
Test with those at risk - low calcium, phosphate, CKD, osteoporosis, primary HPTH, secondary HPTH, obesity, malabsorption syndrome
Test for effects of deficiency as well: PTH, calcium, phosphorous, ALP
Excessive serum vitamin D = hypercalciuria, hypercalcemia, hyperphosphatemia, possible risk of falls
Imaging: Looser lines, transverse pseudo-fracture lines
vitamin d deficiency
how do you treat vitamin d deficiency
D3>D2 in serum levels
– increased dose if patient is obese, has malabsorption syndrome, or is taking meds affecting metabolism
Calcitriol orally or IV with chronic renal failure, nephrotic syndrome, or severe other syndromes, severe liver disease, impaired hepatic metabolism
UV light
Monitoring: 10-12 weeks after starting replacement therapy, consider monitoring for toxicities
Prevent = dietary intake (fatty fish, cod liver oil, egg yolks, sun-exposed mushrooms, fortified foods), sun exposure
Areflexia, disturbances of gait, decreased vibration and proprioception, ophthalmoplegia
vitamin e deficiency
Adults = severe malabsorption or abetalipoproteinemia
Children = chronic cholestatic liver disease, biliary atresia, CF
vitamin e deficiency
Plasma E levels .5-.7 or higher
Toxicity >400/day → require Vitamin K to minimize antiplatelet action
vitamin e deficiency
how do you treat vitamin e deficiency
large doses PO
Epistaxis, menorrhagia, hematuria
vitamin K deficiency
Deficient intake of vitamin K (leafy green vegetables, soybean), malabsorption, decreased production by intestinal bacteria from chemo or abx
vitamin K deficiency
Prolonged PT and aPTT, clotting factors low
vitamin K deficiency
how do you treat vitamin K deficiency
Vitamin K1 IV or PO
Oral dose
IV administration = faster normalized PT (low dose and slowly due to risk of anaphylaxis)
Measurable reduction of levels of phosphorus, potassium and/or magnesium, or manifestation of thiamine deficiency developing shortly (hours to days) after initiation of calorie provision to those exposed to undernourishment
refeeding syndrome
how do you treat refeeding syndrome
Start feeds at low rate (~50%), with empiric thiamine and electrolyte administration
Risk is greatest in first 72 hours – 2x/day electrolyte checks and generous electrolyte replenishment if low levels are identified
Fever, lymphadenopathy, migratory arthralgias, diarrhea, abdominal pain, weight loss due to protein losing enteropathy, edema
Cardiac or CNS involvement
4 cardinal manifestations: arthralgias, abdominal pain/diarrhea, malabsorption, CNS involvement (movement of eyes while eating)
whipple disease
White men 40-60 in North America/Europe
Wastewater contact
Caused by infection with bacillus Tropheryma whipplei
whipple disease
PE: hyperpigmentation of exposed skin
PCR, biopsy of duodenum
whipple disease
how do you treat whipple disease
Antibiotics for a year – ceftriaxone IV for 14 days
Bactrim PO x 12 months
None or unexplained diarrhea and WL, bloating flatulence
IBS
Overgrowth of bacteria in normally sterile segments of small bowel; malabsorption of fat with steatorrhea from abnormal anatomy, dysmotility (diabetes), Crohn’s disease, PPI use
small intestinal bacterial overgrowth
Breath testing of hydrogen and methane is used for
small intestinal bacterial overgrowth
how do you treat SIBO
Cipro, augmentin, bactrim x 7-10 days
Weight loss, diarrhea, electrolyte/water/nutritional deficiencies
–Duodenum absorbs folate, iron, calcium
–Terminal ileum absorbs b12
short bowel/short gut syndrome
Removal of >50% of small bowel
Prior bowel resection
short gut/bowel syndrome
how do you treat short gut/bowel syndrome
Supplemental IV B12, modified diet, loperamide
Teduglutide
Parenteral nutrition → mortality
Diarrhea, bloating, flatulence, abdominal pain after ingestion of dairy products
lactase deficiency
Asian americans
Blacks
Native americans
Secondary to Crohn’s, celiac, viral gastroenteritis, giardiasis, short bowel syndrome, malnutrition
lactase deficiency
Stool specimens – check osmotic gap (increased, pH <6)
Improve with lactose-free diet
lactase deficiency
how do you treat lactase deficiency
Lactose free diet (counsel on dietary calcium), lactase supplements
“Classic” symptoms in infants: diarrhea, steatorrhea, weight loss, abdominal distention, weakness, muscle wasting, growth retardation
“Silent”
Other: chronic diarrhea, constipation, dyspepsia, fatigue, depression, IDA, osteoporosis, amenorrhea, infertility, dermatitis herpetiformis, rash
celiac disease
Autoimmune illness = Hashimoto’s, DMT1 (should be screened annually for celiac disease), celiac
Link to EBV and other viral illnesses – immunologic response to gluten
True celiac = wheat, barley, rye
celiac disease
PE: distended abdomen, hyperactive bowels
Skin – dermatitis herpetiformis
Pallor due to anemia, easy bruising (vitamin K def), hyperkeratosis (vitamin A def), bone pain, neurological signs due to vitamin B12 or vitamin E deficiency
LABS: CBC, PT, albumin, iron, ferritin, calcium, ALP, folate, B12, A, D
IgA tissue transglutaminase-2 antibody (IgA anti-tTG2) if patient NOT already on strict gluten-free diet
Biopsy of EGD of duodenum needed for confirmation of serologic testing is + or suspected false negative with present abnormalities
celiac disease
how do you treat celiac disease
Gluten free diet with no cross-contamination
– avoid dairy/take lactase until intestinal symptoms have improved
Rechallenge w/ gluten may trigger severe diarrhea with dehydration and electrolyte imbalance and may require TPN and IV/oral steroids
Annual monitoring: CBC, CMP, gastric bypass lab panel
DEXA
→ high risk of osteoporosis or osteopenia
→ high association of other AI illness, autoimmune hepatitis
→ Can develop to intestinal T-cell lymphoma
Within 2 hours of ingestion – more common in children
Combo of emesis, diarrhea, urticaria, w/ or w/o angioedema, bronchial hypersensitivity, HOTN
immediate hypersensitivity reaction
Adults: shellfish, peanuts, tree nuts
Children: milk and eggs, but often resolve
immediate hypersensitivity reaction
Known seasonal allergies and itching of oral mucosa upon ingestion of cross-reactive raw fruits and vegetables
Oral allergy syndrome: pollen-associated food allergy from cross-reactivity
Lip swelling, sneezing, itchy eyes, upset stomach, hives, possible anaphylaxis
latex- fruit syndrome: Cross-reactivity with latex to avocado, chestnuts, bananas, kiwi, papaya
2-12 hours after ingestion (3-6 hours generally), heavily influenced by cofactors (alcohol, exercise)
Alpha-gal syndrome: Galactose-alpha-1, 3-galactose in mammal derived meats (beef, pork, lamb, whale, mutton, squirrel) – Lone Star tick bites
History + skin tests + serum-specific IgE tests
→ frequent false positives among eczema patients
Oral food challenge with reproducible reaction is gold standard
allergic reaction
how to treat an allergic reaction
Avoidance of food including cross-contamination with guaranteed access to epinephrine injector at all times
Refer to immunologist for immunotherapy
