VITAMINS AND MALABSORPTION Flashcards
1
Q
what are vitamins
A
- Organic substances that cannot be synthesized by the human body.
- Essential to be ingested in our diets in small quantities to facilitate normal metabolism
- Vitamins are divided into two categories
- Fat soluble vitamins
- Vitamin A, D, E, K
- Water soluble vitamins
- B vitamins & vitamin C
2
Q
vitamin a
A
Subclass of lipid soluble compound called retinoic acids. Vitamin A is
found in plants in form of provitamins (B-carotene) and in preformed
vitamins (retinols; more active form) in animal sources.
* Metabolism
picture
3
Q
vitamin a actions
A
- Eye
- Cell-Differentiation
- Maintenance of skin, mucus membranes
- Key nutrient for fetal development during pregnancy
4
Q
vitamin a deficiency
A
- Vitamin A deficiency is rare in USA or in other resource rich countries
- serum retinol levels (<20 micrograms/dL [0.7 micromol/L] suggest deficiency
- Can sometimes be seen in bariatric patients who have had procedures. These patients are routinely supplemented with multivitamins.
- Biliopancreatic diversion
- Gastric Bypass
- Patients with disorders associated with fat malabsorption
- Cystic fibrosis
- Pancreatic insufficiency
- Celiac disease
- Cholestatic liver disease
- Primary cholangitis
- Small bowel Chrohn disease
- Short bowel syndrome
- Bariatric surgery
- Vitamin A deficiency is higher among other places of the world
- approximately 30 percent among children under age 5 worldwide
Nearly 50 percent in young children in South Asia and sub-Saharan Africa1
5
Q
sx vitamin a deficiency
A
- Night blindness, complete blindness, xerophthalmia
- Delayed growth, poor bone growth
- Dry Skin, hair
- Weakened immune system
6
Q
Vitamin A Deficiency Treatment and
Toxicity
A
- Treatment
- In endemic areas, 100,000 – 200,000 IU (30
mg – 60 mg) Retinol, periodic
supplementation - Eating foods rich in Vitamin A
- Toxicity
- Very rare to have from excess ingestion
- Acute toxicity occurs in adults when a single
dose of >660,000 IU of vitamin A ingested - Symptoms: nausea, vomiting, vertigo, blurry
vision, malaise, drowsiness - Accutane
- Teratogenic effects
7
Q
Vitamin B1
(thiamine)
A
- Acts as a catalyst for converting Pyruvate
to Acetyl CoA - Thiamine has an unidentified role in the
initiation of nerve impulse propagation
that is independent of its coenzyme
functions. - Absorbed in the small intestines. Passes
through the intestines into the blood and is
then phosphorylated into its active form.
Thiamine then enters the target cells via
active transport or passive diffusion. - The highest concentrations are found
in the skeletal muscles, the liver, the
heart, the kidneys, and the brain.
8
Q
Signs and
Symptoms of
Thiamine deficiency
A
- Deficiency may develop in as little as 3
to 14 days - Normal level ranges from 70 -180
nmol/L (3.0 to 7.7 mcg/dL) - Thiamine deficiency in the diet causes
two clinical phenotypes: - Beriberi (infantile and adult)
- Wernicke-Korsakoff syndrome
9
Q
BeriBeri
A
- Infantile
- Mainly in breastfed infants from moms who do not have sufficient thiamine in diet
- Symptoms
- Fulminant cardiac syndrome: cardiomegaly, tachycardia, a loud piercing cry, cyanosis,
dyspnea, vomiting and pulmonary hypertension - Older infants: neurologic symptoms resembling aseptic meningitis, including agitation,
an aphonic (soundless) cry, vomiting, nystagmus, purposeless movements, altered
consciousness, and seizure, with no abnormalities on cerebrospinal fluid analysis - Treatment
- IV Thiamine 100 to 200 mg TID x 2-3 days,
followed by maintenance therapy PO: 5-30 mg
once daily until no longer at risk for deficiency
- IV Thiamine 100 to 200 mg TID x 2-3 days,
10
Q
beriberi wet v dry
A
- Adults with two phenotypes “dry” or “wet”
- Can happen in adults as complication of weight loss surgery,
chronically hospitalized patients - Dry
- symmetrical peripheral neuropathy characterized by both sensory and motor
impairments, mostly of the distal extremities - Wet
- cardiomegaly, cardiomyopathy, heart failure, peripheral edema, and tachycardia, in
addition to neuropathy
11
Q
Wernicke-Korsakoff syndrome
A
- Neurologic complication of thiamine deficiency
- Wernicke encephalopathy (WE) is an acute syndrome requiring emergency
treatment to prevent death and neurologic morbidity. - nystagmus, ophthalmoplegia, ataxia, and confusion
- Korsakoff syndrome refers to a chronic neurologic condition that usually
occurs as a consequence of WE. - Reported in those with chronic alcohol use disorder and as a consequence
of bariatric surgery - Treatment
- IV Thiamine 200-500 mg TID x 2-7 days, followed by 250 mg QD 3 to 5 days, followed
by maintenance therapy, 100 mg QD until no longer at risk for deficiency
12
Q
Thiamine deficiency in alcoholics
A
- Alcoholics may develop a thiamine deficit because of impaired thiamine absorption from the intestine.
- Alcohol damages the lining of the intestines
- Nutritional thiamine deficiency can occur due to poor eating habits.
- Foods that are high in carbohydrates and low in vitamins
- Metabolism of carbohydrates are thiamine requiring enzymes
- Patients hospitalized for alcohol withdrawal are at high risk for developing
Wernicke encephalopathy - Usually treated with IV or PO 100 - 200 mg Thiamine QD x 3-5 days as preventative
- Those with clinical signs of malnutrition, liver disease, daily alcohol consumption
- PO thiamine 100mg tid, as ongoing supplementary therapy
13
Q
Vitamin C (ascorbic acid)
A
- Water soluble vitamin
- Ascorbic acid is absorbed in the distal small intestine
through an energy-dependent active transport process.
Usual dietary doses of up to 100 mg/day are almost
completely absorbed - Blood concentrations of ascorbic acid are regulated by renal excretion.
- Ascorbic acid is a reversible biologic reducing agent
(electron donor), which is important to maintain the activity of several enzymes that include iron and copper - Involved in many biological processes: fatty acid transport, collagen synthesis, neurotransmitter synthesis, prostaglandin metabolism, nitric oxide synthesis
- Historical Context
- Captain James Cook
14
Q
Vitamin C deficiency syndrome known as
Scurvy
A
- Largely due to impaired collagen synthesis and disordered connective tissue.
- Symptoms of scurvy generally occur when the plasma concentration of ascorbic acid is less than 0.2 mg/dL (11 micromol/L)
- Symptoms noticeable after 3 months of deficiency
- cutaneous signs (petechiae, perifollicular hemorrhage, and bruising)
- Gingivitis
- Arthralgias
- Limping in children/refusal to walk
- Impaired wound healing
15
Q
Scurvy
A
- In the US, deficiency is rare but can happen in
- drug and alcohol use disorders
- bariatric surgery
- living in poverty or on diets devoid of fruits and vegetables
- Institutionalized
- Chronically ill
- Children with autism with highly selective diets devoid of fruits/vegetables
- Treatment
- Peds
- 100 mg ascorbic acid TID (PO, IM or IV) x 7d, then QD for several weeks until the patient is fully recovered
- Adults
- 300-1000mg QD x 1 month
16
Q
vitamin d
A
- Fat soluble vitamin
- Dermal synthesis is major source
- Fewer naturally occurring foods
sources that contain vitamin D - Vitamin D sufficiency is defined
as a 25(OH)D concentration ≥20
ng/mL (50 nmol/L)
17
Q
Mechanism of action and
pathophysiology of Vitamin D
A
- Dietary vitamin D is incorporated into micelles, absorbed by enterocytes (small intestines), and then packaged into chylomicrons.
- Liver & kidneys activate vitamin D into its active
metabolite via hydroxylation
Vitamin D enhances intestinal absorption of calcium and phosphate. Low concentrations of vitamin D are associated with impaired calcium absorption, a negative calcium balance, and a compensatory rise in parathyroid hormone (PTH), which results in excessive bone resorption.
18
Q
Causes of Vitamin D
deficiency
A
- Decreased intake or absorption
- Reduced sun exposure
- Increased hepatic catabolism
- Decreased endogenous synthesis of active form (via
decreased 25-hydroxylation in the liver or 1- hydroxylation in the kidney) - End-organ resistance to vitamin D
- mutations in the vitamin D receptorrickets despite
adequate vitamin D intake - Higher risk patients
- institutionalized
- obesity
- increased skin pigmentation
- Higher melanin absorbs less UVR*
- malabsorption syndromes (IBD, celiac disease)
19
Q
Symptoms of severe prolonged Vitamin D
deficiency:
A
- Reduced intestinal absorption of calcium and phosphorus and hypocalcemia (Secondary hyperparathyroidism)
- Demineralization of bones
- Osteomalacia in adults and rickets
- bone pain and tenderness, muscle weakness, fracture, and difficulty walking
20
Q
Evaluation and Management vitamin d
A
- Routine lab that is drawn at many wellness/physical exams
- 25-hydroxyvitamin D (25[OH]D) levels of 12 - <20 ng/mL do not require any
additional evaluation - patients with levels under 20 are at some risk for oseteomalacia
- patients under <12 ng/mL
- serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH),
electrolytes, blood urea nitrogen (BUN), creatinine, and tissue transglutaminase antibodies (to assess for celiac disease)
21
Q
Lactose intolerance
A
Lactose intolerance – A clinical syndrome in which ingestion of lactose or lactose-containing food causes symptoms (abdominal pain, bloating, flatulence, nausea, diarrhea). Lactose intolerance may or may not be associated with lactose malabsorption
22
Q
Pathophysiology of lactose
intolerance:
A
- ingested Lactose is hydrolyzed by Lactase in the intestines
and converted into monosaccharides glucose & galactose.
These are then taken up into the cells of the small intestine - In individuals with low lactase activity, ingested lactose, about 75% of it, bypass the SI and goes into the colon where it is converted to short chain fatty acids & hydrogen gas by intestinal bacteria.
- Accumulation of lactose & its fermentation causes
the symptoms of intolerance - Epidemiology:
- lowest prevalence in Europeans and European
Americans - higher prevalence in African Americans, Asian
Americans, and Native Americans
23
Q
Clinical Manifestations lactose intolerance
A
Within few hours of ingestion:
* Abdominal pain
* Crampy, usually periumbilical or to lower quadrants of abdomen
* Bloating
* Nausea
* Diarrhea
* More common in children, may be bulky/watery
* Flatulence
24
Q
Management of Lactose Intolerance
A
- Diet restriction
- Avoid completely
- Limit milk to 2 cups or less (or its lactose equivalent in
cheese and other lactose-containing food items - Take in divided doses
- Individuals may start with more strict dietary restriction and then work up to their individually tolerated limit of ingestion of lactose-containing food.
- Different foods contain different levels of lactose
for example, mozzarella cheese has less
lactose than cottage cheese - Vitamin D & Calcium should be supplemented in those who avoid dairy
- Lactase enzyme supplementation
- Lactaid
- Cow’s milk + Lactase; which breaks down the lactose
into sugars that are easier to digest
Malabsorption - Intestinal absorption refers to the assimilation of dietary fats, carbohydrates, proteins, vitamins, minerals, and trace elements into the systemic circulation.
25
Q
Malabsorption
A
- Intestinal absorption refers to the
assimilation of dietary fats,
carbohydrates, proteins, vitamins,
minerals, and trace elements into
the systemic circulation. - Malabsorption refers to impaired
transport of nutrients into the small
intestines.
26
Q
Fats
A
- Ingested fats need to be in soluble form to digested
(emulsified) - Mastication
- Coated by gastric fluid
- Emulsified fats are then move to the stomach where
it is exposed to gastric lipase and in the duodenum
to pancreatic lipase. Triglycerides are broken down
into 2 monoglyceride and 2 fatty acids - The resulting mixture is a complex soup of lipolytic
products. These products are mixed with bile salts
to form micelles and are taken into enterocytes.
Ideally in a pH of 6.5 - Once taken up by peripheral tissues, can be used
by muscles for energy or be stored in adipose
tissue
27
Q
Causes of Fat malabsorption
A
- Decreased optimal duodenal pH <6.5
- Zollinger Ellison syndrome
- Decreased intestinal surface area
* Crohn disease
* Celiac
* Ulcerative colitis
* Small bowel resection - Impaired lipid processing by bile acids
* Liver disease
* Cholestasis - Small intestinal bacterial overgrowth
* Deconjugate bile acids, bile acids cannot absorb fats - Pancreatic insufficiency/cancer
- Lymphatic system disorders
* Intestinal lymphangiectasia
* Whipple disease
28
Q
Crohn’s Disease
A
- Form of an inflammatory bowel disease
- CD is characterized by transmural inflammation and
may involve any portion of luminal gastrointestinal
tract, from the oral cavity to the perianal area. - The pathophysiology is multifactorial
- Relating to fat malabsorption
- Bile acids form mixed micelles together with fatty acids, which function as a transport vehicle to deliver fatty acids to the apical membrane of enterocytes for absorption. Therefore, if the terminal ileum is impaired, bile acid malabsorption may occur, which may cause congenital diarrhoea in Crohn’s disease.
29
Q
Fat malabsorption symptoms
A
- Steatorrhea
- Large pale stools/ “heavy stool”
- In Average, 200 grams for female adults and 220 grams for males. Patients
with steatorrhea almost always have stool weights in excess of these values - Diarrhea without flatulence
30
Q
Carbohydrates
A
- Complex carbohydrates such as sucrose, starch, lactose are broken down into their monosaccharides prior to absorption
- Salivary and pancreatic amylase aid in breakdown of complex carbohydrates
- Carbohydrates that are not broken down in the
SI and absorbed undergoes bacterial degradation in the colon. - Hydrogen and methane produced from fermentation of unabsorbed carbohydrates
- This is excreted by the lungs. Non- invasive breath tests can be used to detect carbohydrate malabsorption.
31
Q
Symptoms of
carbohydrate
malabsorption
A
- Acidic stools
- Abdominal distension
- flatulence
- Diarrhea
32
Q
causes of carbohydrate malabsorption
A
- Deficiency in pancreatic amylase
- Reduced disaccharidase activity in the small intestinal epithelium
- Can co-exist in conditions such as IBD, colitis
- Decreased absorptive intestinal surface area
- eg, celiac disease
- Unabsorbable carbohydrates
- Low-digestible carbohydrates are carbohydrates that are incompletely
or not absorbed in the small intestine but are at least partly fermented by bacteria in the large intestine. Fiber, resistant starch, and sugar alcohols are types of low-digestible carbohydrates.
33
Q
Celiac disease
A
- Immune disorder triggered by gluten in
genetically predisposed individuals - Gliadin fractions (component of gluten)
promote an inflammatory reaction causing
chronic inflammatory cells and villous
atrophy in SI.
34
Q
Proteins
A
- Starts in the stomach with gastric pepsin which
releases amino acids - amino acids released from gastric digestion play a role in releasing cholecystokinin (CCK)
- CCK is critical for stimulating the release of pancreatic enzymes responsible for the digestion of all three macronutrients.
- In the duodenum, several proteases act together to digest proteins into amino acids, or dipeptides and tripeptides.
- After breakdown into amino acids, dipeptides, and tripeptides, these are absorbed at the brush border membrane by secondary active transport
35
Q
causes of protein malabsorption
A
- Pancreatic bicarbonate and protease secretion and/or activity is impaired
- Chronic pancreatitis
- Cystic Fibrosis
- Diseases associated with a generalized reduction of the intestinal absorptive surface
- Bowel resection
- Crohn’s disease
36
Q
Cystic
fibrosis
A
Multisystem disorder caused by
gene mutations resulting in
abnormal transport of chloride
and sodium across secretory
epithelia. This causes thickened,
viscous secretions in the bronchi,
biliary tract, pancreas, intestines,
and reproductive system
37
Q
Protein malabsorption symptoms
A
- Edema, hypoalbuminemia
- Muscle atrophy
- Amenorrhea
- Chronic systemic illness such as IBD & celiac can cause inhibition of hypothalamic secretion and leads to amenorrhea.
- Severe states
- Pleural effusions
- Ascites
38
Q
Workup of
malabsorption
A
If there is suspicion for malabsorption
syndromes based on history and physical
can approach the patient first with general
testing. Symptoms can be vague such as
unintentional weight loss, ongoing
diarrhea, chronic abdominal pain
Blood work
CBC
CMP
Albumin
Mg
Zinc
Phos
Vitamin b12, folate, vitamin D
Iron panel
Fecal tests (most sensitive for fat malabsorption)
Fecal fat
72 hr fecal fat excretion – gold standard
Breath tests
* Carbohydrate malabsorption syndromes
* Positive glucose or lactulose breath test
* Jejunal aspirate culture
* Gold standard for SIBO
* CT
* Pancreatitis
* MRCP
* Pancreatic insufficiency
* Endoscopy/colonoscopy
* Crohn’s disease, Celiac disease, ulcerative colitis
39
Q
Malabsorption Management
A
- Treatment targets correcting deficiencies, treating the
underlying cause, avoiding triggers (typically dietary), and treating symptoms (e,g often diarrhea). - Celiac disease: avoid gluten
- Zollinger Ellison: PPI to reduce acidity to improve fat absorption
- Pancreatic insufficiency: pancreatic enzyme replacement
- SIBO: antibiotics
- Diarrhea
- Loperamide or diphenoxylate with atropine if severe
- Oral Rehydration
