Nutritional Pathology

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


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)


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



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


Both Marasmus and Kwashiorkor

Stunted growth Anemia Infections and defects in immunity Multi-vitamin deficiencies



In the public domain, Centers for Disease Control, www.cdc.gov


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


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


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


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)


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)


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)



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



Enhances immunity to infections

Related carotenoids are photoprotective and anti-oxidants

Immune deficiency Higher mortality

rates from measles, pneumonia, and infectious diarrhea


Vitamin A Deficiency


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


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


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)


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


Normal Vitamin D Metabolism


Vitamin D Deficiency


Rickets


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)


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


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


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


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


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


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)


Beriberi (Thiamine Deficiency)


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


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)


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


Niacin (B3) Deficiency(Pellagra)


Pyridoxine (B6)

Clinically overt deficiency of vitamin B6 is rare

in humans

Findings resemble riboflavin (B2) and

niacin (B3) deficiency


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


Vitamin C Deficiency(Scurvy)


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”


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


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


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)


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


Zinc Deficiency


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


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


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)


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)


Health & Medicine

Nutritional Pathology