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Nutritional Pathology
James L. Fishback, M.D.
Associate Professor
University of Kansas School of Medicine
Food Safety Numerous natural constituents, toxic substances, and
food additives may threaten human health: Carcinogens (safrole in nutmeg, estragole in basil) Natural pesticides (celery, parsnips, parsley) Toxicants (aflatoxin, botulinum) Microorganisms (E. coli, Salmonella, etc.) Additives (colors, sweeteners, preservatives) Indirect additives (residual hormones, drugs,
pesticides, packaging residue) Industrial contaminants (PCBs, etc.)
04/11/23 © 2009, James L. Fishback, M.D.
Nutritional Deficiencies
Protein energy (calorie) malnutrition (PEM) Anorexia nervosa and bulimia Vitamin deficiencies (more common in
alcoholics) Mineral deficiencies
04/11/23 © 2009, James L. Fishback, M.D.
Protein-Energy Malnutrition (PEM) Inadequate intake of protein and calories to meet the
body’s needs Most common in underdeveloped and developing
countries Up to 25% of children may be affected Major cause of death in children < 5yrs Associated with diarrheal diseases
Less common in developed countries Associated with poverty, alcoholism, ignorance,
acute or chronic illness, and voluntary diet restriction
A child with weight < 80% normal is malnourished04/11/23 © 2009, James L. Fishback, M.D.
Protein Compartments
Somatic protein compartment Skeletal muscles
Visceral protein compartment Protein stores in organs (predominantly
liver)
04/11/23 © 2009, James L. Fishback, M.D.
Marasmus Kwashiorkor
Deficiency of total food intake
Deficiency of protein intake Babies who are weaned early
(many times because of arrival of another child) and then fed an exclusively carbohydrate diet
Less severe forms can occur with chronic diarrhea (where
protein is not absorbed) protein losing
enteropathies nephrotic syndrome
04/11/23 © 2009, James L. Fishback, M.D.
Marasmus Kwashiorkor
Somatic protein compartment more severely impacted Spindly arms and legs
Serum albumin normal or slightly reduced
Visceral protein compartment more severely impacted Apathy, listlessness, loss of
appetite Enlarged fatty liver
Hypoalbuminemia Anasarca
Other characteristics Skin: alternating zones of
hyperpigmentation, desquamation
Hair: loss of color or alternating bands of pale and darker hair
04/11/23 © 2009, James L. Fishback, M.D.
Both Marasmus and Kwashiorkor
Stunted growth Anemia Infections and defects in immunity Multi-vitamin deficiencies
04/11/23 © 2009, James L. Fishback, M.D.
Marasmus Kwashiorkor
In the public domain, Centers for Disease Control, www.cdc.gov
04/11/23 © 2009, James L. Fishback, M.D.
Secondary Protein-Energy Malnutrition Common in chronically ill and hospitalized patients
Increased basal metabolic rate (cytokines, tumor necrosis factor, etc.)
Cachexia (Marasmus-like PEM) Usually seen in setting of AIDS, cancer, end-stage
lung disease (e.g, emphysema). Depletion of subcutaneous fat, muscle wasting
and ankle or sacral edema Kwashiorkor-like PEM
Usually seen with severe trauma, burns, sepsis Edema, serum albumin < 2.8 gm/dL
04/11/23 © 2009, James L. Fishback, M.D.
Anorexia Nervosa Bulimia
Self-induced starvation (PEM-like findings)
Amenorrhea Decreased thyroid hormone
release Cold intolerance, bradycardia,
constipation, dry scaly skin, lanugo body hair
Decreased bone density Anemia, lymphopenia Hypoalbuminemia
Binge eating followed by induced vomiting
Menstrual irregularities Vomiting complications
Pulmonary aspiration of gastric contents
Esophageal and cardiac rupture
04/11/23 © 2009, James L. Fishback, M.D.
Anorexia and Bulimia
Anorexia: approx 1% of adolescent females Bulimia: approx 4% of college-aged females Approx 10% with anorexia or bulimia are
male Prone to hypokalemia
Increased risk of sudden death due to cardiac arrhythmia
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin Deficiencies 13 vitamins are essential for health
Vitamins A, D, E, and K are fat soluble Vitamin C and the 8 B-complex vitamins are water soluble Deficiencies in a single vitamin are uncommon Deficiencies can be submerged in PEM
These vitamins must be supplied in the diet Exception: small amounts of D, K, biotin and niacin can be
synthesized endogenously Vitamin D from UV light Vitamin K and biotin from intestinal microflora Niacin from tryptophan (amino acid)
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin A
Group of related natural and synthetic chemicals with hormone-like activity
Dietary sources Pre-formed vitamin A
animal derived (liver, fish, eggs, milk, butter) Carotenoids (e.g., beta-carotene) for synthesis
of vitamin Ayellow and leafy green vegetables (carrots,
squash and spinach)
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin AFunctions Deficiency
Maintains normal vision Reduced light
Vitamin A (retinol) -containing pigments rhodopsin (rod
cells) and iodopsins (cone cells)
Maintains ocular epithelium (lubrication, corneal)
Impaired vision (early manifestation) Night blindness
Xerophthalmia (dry), keratin build-up (Bitot spots), keratomalacia, and eventual blindness (erosion of the roughened cornea)
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin AFunctions Deficiency
Differentiation of epithelial cells Maintains respiratory
epithelium (mucociliary)
Maintains urothelium Healthy epidermis
(skin)
Deficiency causes squamous metaplasia Loss of function
predisposes to pulmonary infections
Hyperplasia and hyperkeratinization Follicular or papular
dermatosis
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin AFunctions Deficiency
Enhances immunity to infections
Related carotenoids are photoprotective and anti-oxidants
Immune deficiency Higher mortality
rates from measles, pneumonia, and infectious diarrhea
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin A Deficiency
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin A Toxicity Acute toxicity
Headache, vomiting, stupor, death Chronic toxicity
Weight loss, vomiting, dryness of lips Bone and joint pain, hyperostosis, hepatomegaly with
fibrosis Predisposition to bone fractures (due to stimulation of
osteoclasts) Congenital malformations
Synthetic retinoids for acne (Accutane™) contraindicated during pregnancy Cause CNS, cardiac and craniofacial defects
04/11/23 © 2009, James L. Fishback, M.D.
Carotenemia
Excess vitamin A precursors Usually from eating too many carrots, or
artificial “suntanning” pills Yellow-orange colored skin (mainly palms
and soles)Sclera remain white (vs. real jaundice)
Not associated with toxicity, even in large amounts
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin DFunction Deficiency
Maintenance of normal plasma levels of calcium and phosphorus
Maintenance of ionized calcium in extracellular compartment
Poor bone mineralization Rickets (if epiphyses have
not closed) Osteomalacia (epiphyses
have closed) Hypocalcemic tetany
Insufficient ionized calcium causes continuous excitation (convulsive state)
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin D
Two sources Endogenous synthesis
Precursor 7-dehydrocholesterol in the skin and UV light
Requires healthy kidneys for conversion to di-hydroxy Vitamin D
Diet
04/11/23 © 2009, James L. Fishback, M.D.
Normal Vitamin D Metabolism
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin D Deficiency
04/11/23 © 2009, James L. Fishback, M.D.
Rickets
04/11/23 © 2009, James L. Fishback, M.D.
Predisposing Conditions for Poorly Mineralized
Bone (Rickets, Osteomalacia) Inadequate synthesis of dietary deficiency of vitamin D
No exposure to sunlight or pigmented skin; limited intake of vitamin D
Decreased vitamin D absorption Cholestatic liver disease, pancreatic insufficiency, biliary tract
obstruction, extensive small bowel disease/severe malabsorption
Derangements of vitamin D metabolism Increased degradation by induction of cytochrome P450 enzymes,
impaired synthesis of 25 and 1,25(OH)2D, inherited deficiency of renal alpha-1 hydroxylase
End-organ resistance Inherited absence of or defective receptors for 1,25(OH)2D
Phosphate depletion Poor phosphate absorption due to aluminum OH antacids Excess renal tubule excretion of phosphate (X-linked
hypophosphatemic rickets)
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin E Functions
Major anti-oxidant (scavenges free radicals)
Sources Vegetables, grains, nuts and their oils, dairy products, fish and meat
Deficiency Usually in association with fat malabsorption that accompanies
cholestasis, cystic fibrosis and primary small intestinal disease Neurologic manifestations
Absent tendon reflexes, ataxia, dysarthria, loss of vibration and position sense and pain sensation
Spinocerebellar degeneration
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin K
Functions Required for functional activity of
clotting factors II, VII, IX, X and protein C and S
Studies suggest it may be helpful in treating osteoporosis It may favor calcification of bone
proteins
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin K Deficiency
Increased risk with Fat malabsorption syndromes Diffuse liver disease Absence of vitamin K-synthesizing bacterial flora
Broad spectrum antibiotics can destroy it Not fully developed in neonates (vitamin K given
prophylactically to all newborns)
Deficiency causes bleeding diathesis (skin, gums, umbilicus, viscera, intracranial) Coumarin (warfarin) induces deficiency
Desirable in thromboembolic disease
04/11/23 © 2009, James L. Fishback, M.D.
B-Complex Vitamins
B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B12 and folate
8 of the 9 water soluble vitamins All function as coenzymes, and needs are tied to
energy intake Not much is present in polished rice, white flour,
white sugar
04/11/23 © 2009, James L. Fishback, M.D.
Thiamine (B1) Deficiency
Uncommon on a dietary basis in developed countries (widely available in diet)
Still occurs in developing countries where polished (white) rice is most of the diet
Major targets of deficiency are nerves, heart and brain Dry beriberi (polyneuropathy)
Classically presents with toe drop, foot drop, wrist drop
Wet beriberi (cardiovascular) Wernicke-Korsakoff syndrome
04/11/23 © 2009, James L. Fishback, M.D.
Beriberi (Thiamine Deficiency)
Common in alcoholics (25% of those admitted) May also occur in
Pernicious vomiting of pregnancy Debilitating diseases that impair appetite,
predispose to vomiting or cause protracted diarrhea
Extended iv glucose therapy without supplemental vitamins (may convert sub-clinical to overt disease in chronically malnourished individuals)
04/11/23 © 2009, James L. Fishback, M.D.
Beriberi (Thiamine Deficiency)
04/11/23 © 2009, James L. Fishback, M.D.
Riboflavin (B2) Sources: meat, dairy, vegetables Absorbed in upper GI tract Ariboflavinosis
Persons in economically deprived developing countries Alcoholics, chronic infections, advanced cancer and
other debilitating diseases, anorexics and individuals
who avoid milk Morphology
Cheliosis (cracks and fissures at angles of mouth) Glossitis (atrophic tongue) Corneal opacities and ulcerations Dermatitis
04/11/23 © 2009, James L. Fishback, M.D.
Niacin (B3)
Sources Grains, legumes, seed oils (small quantities in meats)
Niacin in corn is in a bound form and unabsorbable Deficency can be seen where corn is most of the
diet Can be synthesized endogenously from tryptophan
A deficiency of tryptophan can mimic niacin deficiency
Deficiency (pellagra) Alcoholics, chronic debilitating diseases (e.g., HIV)
04/11/23 © 2009, James L. Fishback, M.D.
Niacin (B3) Deficiency(Pellagra)
Three D’s: Dermatitis
Thickened red rough skin, bilaterally symetric on exposed areas of the body
DiarrheaAtrophy of columnar epithelium of GI
tract Dementia
04/11/23 © 2009, James L. Fishback, M.D.
Niacin (B3) Deficiency(Pellagra)
04/11/23 © 2009, James L. Fishback, M.D.
Pyridoxine (B6)
Clinically overt deficiency of vitamin B6 is rare
in humans
Findings resemble riboflavin (B2) and
niacin (B3) deficiency
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin C (Ascorbic Acid) Functions: formation of normal collagen,
antioxidant Deficiency disease is called scurvy
UncommonThose most at risk are elderly who live
alone, alcoholics, infants fed exclusively processed milk
Used to be seen with long sea voyages Symptoms reversible almost immediately
with vitamin C04/11/23 © 2009, James L. Fishback, M.D.
Scurvy (Vitamin C Deficiency) Poor wound healing – poor collagen synthesis Ecchymoses and purpura in skin and gingival
mucosa (small vessels have defective collagen) Secondary gum infections Papular rash
Sub-periosteal hematomas and hemarthrosis after minimal trauma
Retrobulbar, subarachnoid and intracerebral hemorrhages (can be fatal)
Skeletal changes due to insufficient osteoid matrix Growing children: bowing of long bones, depression of the
sternum with outward projection of the ends of the ribs
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin C Deficiency(Scurvy)
04/11/23 © 2009, James L. Fishback, M.D.
Vitamin Deficiency ComparisonVit C Vit D
Poor osteoid production Bowing of long
bones of lower legs Depression of
sternum with outward projection of ribs
Poor mineralization (calcification of bone) Bowing of long bones
of lower legs Protrusion of sternum
with overgrowth of cartilage at costochondral junction “rachitic rosary”
04/11/23 © 2009, James L. Fishback, M.D.
Folate Sources
Whole-wheat flour, beans, nuts, liver, green leafy vegetables
Depleted in cooked and processed foods In the U.S. 15-20% of adults probably have
a low level Folate requirement is increased during
pregnancy!Deficiency can predispose to fetal
neural tube defects04/11/23 © 2009, James L. Fishback, M.D.
Vitamin B12 Deficiency
Sub-acute combined degeneration of the spinal cord Potentially reversible Numbness and tingling in the lower
extremities progressing to spastic weakness and then paraplegia
Degeneration of both ascending and descending tracts of the spinal cord
04/11/23 © 2009, James L. Fishback, M.D.
Subacute combined degeneration or Posterolateral myelopathy of B12 deficiency
Mineral Deficiencies
Many trace minerals are found within the body Deficiencies can occur due to
Inadequate supplementation in total parenteral nutrition (TPN)
Interference with absorption by dietary constituents
Inborn errors of metabolism leading to abnormal absorption
04/11/23 © 2009, James L. Fishback, M.D.
Mineral Deficiencies
5 minerals are associated with well-characterized deficiency states Iron, zinc, copper, selenium and iodine
Iron deficiency is most common in U.S. In children, usually inadequate intake In adults, usually blood loss or
pregnancyHypochromic microcytic anemia
(defective heme synthesis)
04/11/23 © 2009, James L. Fishback, M.D.
Zinc Deficiency
Abundant in the diet: meat, shellfish, fish, whole-grain cereals, legumes
Deficiency usually due to TPN unsupplemented by zinc Congenital zinc deficiency (auto recessive, rare)
Findings Acrodermatitis enteropathica
Rash around eyes, nose mouth and anus Anorexia, diarrhea, growth retardation, impaired
night vision, depressed mental function
04/11/23 © 2009, James L. Fishback, M.D.
Zinc Deficiency
04/11/23 © 2009, James L. Fishback, M.D.
Selenium Deficiency
Anti-oxidant (like vitamin E and C) Deficiency is known as Keshan disease
Results from low level in soil, water and food
Congestive cardiomyopathyMainly in children and young women
04/11/23 © 2009, James L. Fishback, M.D.
Obesity
Food derived energy chronically exceeds energy expenditure
Global epidemic Sedentary lifestyles, improved socioeconomic
conditions, high calorie fast foods and soft drinks 30% of adults in U.S. are obese
Body mass index (BMI) >30 kg/m2
Hypertension, diabetes and coronary artery disease begin to increase at BMI values > 25
04/11/23 © 2009, James L. Fishback, M.D.
Obesity
Etiology is extremely complex Genetic, environmental and psychological
factors Central or visceral obesity has a higher risk
for disease (vs. diffusely increased subcutaneous fat)
04/11/23 © 2009, James L. Fishback, M.D.
Complications of Obesity
Syndrome X (metabolic syndrome) Abdominal obesity, insulin resistance,
hypertriglyceridemia, low HDL, hypertension, coronary artery disease
Gallstones, pancreatitis, fatty liver, Congestive heart failure, arrhythmias, deep vein thrombosis
(and subsequent pulmonary embolus), ischemic stroke Obesity hypoventilation syndrome, sleep apnea Osteoarthritis, gout Endometrial cancer (excess estrogen,
difficulty in screening)
04/11/23 © 2009, James L. Fishback, M.D.