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Nutritional Pathology Topics

• Nutritional deficiencies – Protein – Energy – Nervosa and Bulimia – Deficiencies – Mineral Deficiencies • Obesity นายแพทย ดร.ณตพล ศุภณัฐเศรษฐกุล • Diet and Systemic Diseases ภาควิชาพยาธิวิทยา คณะแพทยศาสตร มหาวิทยาลัยนเรศวร

12 กันยายน พ.ศ. 2555

Nutritional deficiencies

An aequate diet should provide: 1. Energy, in the form of carbohydrates, fats, proteins 2. Essential (as well as nonessential) amino acids and fatty acids as building blocks 3. and minerals function as coenzymes and hormones in vital metabolic pathways

http://www.easy-weightloss-tips.com/images/diabetic-food-pyramid.jpg

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ภาวะทุพโภชนาการ (Malnutrition) Common Causes

Primary malnutrition : missing from the diet • (homeless, aged, children) • Ignorance Secondary malnutrition : adequate nutrients (infants, adolescents, pregnant women) supply, but malnutrition may result from - Malabsorption • Chronic alcoholism - Impaired nutrient use or storage • Acute and chronic illnesses - Excess nutrient losses (trauma, burn, cancer, etc.) - Increased need for nutrients • Self-imposed dietary restriction (GI diseases, chronic wasting diseases, acute critical illness)

Protein - Energy malnutrition (PEM)

- PEM refers to a range of clinical syndrome characterized by an inadequate dietary intake of protein and calories to meet the body’s needs.

- Primary (children) and Secondary (illness) PEM

- Two polar forms: - Marasmus, - A B

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1. Marasmus.

- Severe reduction in caloric intake - Greater than 60% reduction in body weight - Most common during the first year of life - Use somatic protein component & subcutaneous fat as a source of energy - Serum albumin levels are either normal or only slightly reduced - Growth retardation, multivitamin deficiencies, Marasmus , immune deficiency

2. Kwashiorkor

- More severe form of malnutrition than marasmus - Mainly occur in children 6 months to 3 years of age - Occurs when protein deprivation is relatively greater than the reduction in total calories - Loss of visceral protein component - Hypoalbuminemia → generalized - Fatty change of liver - Skin lesion : hypo-and hyperpigmentation, desquamation - Hair change : overall loss of color or alternating band (flag sign), straightening, loss of firm attachment to the scalp - Multivitamin deficiencies, anemia, immune deficiency

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Secondary PEM.

Syndrome Clinical Time Clinical features Laboratory Prognosis setting course findings

1. marasmus- Chronic Months History of weight Normal or Variable; like PEM illness (e.g., loss, muscle mildly depends chronic lung wasting, absent reduced on disease, subcutaneous fat serum underlying cancer) “” proteins disease

2. kwashiorkor- Acute, Weeks Normal fat and Serum poor like PEM catabolic muscle , edema, albumin Kwashiorkor illness (e.g., easily pluckable  2.8 gm/dl severe hair trauma, burn, sepsis)

Topics Anorexia Nervosa

• Nutritional deficiencies • Self-induced , resulting in marked – Protein – Energy Malnutrition – Anorexia Nervosa and Bulimia • Manifested as severe PEM with endocrine – Vitamin Deficiencies abnormalities – Mineral Deficiencies – Amenorrhea (GnRH, LH, FSH) – Decreased bone density (low estrogen level) • Obesity – Decreased thyroid hormone release (cold intolerance, bradycardia, constipation) • Diet and Systemic Diseases • Increased susceptibility to cardiac arrhythmia and sudden death

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http://www.funatiq.com/images/anorexia-nervosa-model.jpg

Anorexia Nervosa

http://www.womenshealthzone.net/eating-disorders/anorexia-nervosa/effects/img/1287.gif http://1.bp.blogspot.com/_cBDzDLF1zns/SE_ELpvdbjI/AAAAAAAAACk/92KsZWfMR8M/S740/normal_00031778.jpg

Bulimia

• A condition in which the patient binges on and then induces vomiting

• Amenorrhea occurs in less than 50% of Pt., Wt. and gonadotropin levels are near normal • Major medical complications: – Electrolyte imbalances () and cardiac arrhythmia – Pulmonary aspiration of gastric content – Esophageal and cardiac rupture

http://www.netscool.com/elrio/daniela/bulimia.jpg

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Topics

• Nutritional deficiencies – Protein – Energy Malnutrition – Anorexia Nervosa and Bulimia – Vitamin Deficiencies Bulimia – Mineral Deficiencies • Obesity • Diet and Systemic Diseases

http://internationalteenlife.pbworks.com/f/bulimia.gif

http://purgingpoet.today.com/files/2009/04/effects_of_bulimia.jpg http://www.topnews.in/files/Bulimia.jpg http://4.bp.blogspot.com/_zRiLerjhL2c/Rh8dELoSWOI/AAAAAAAAAVM/BoGHNraqwwQ/s400/bulimia.bmp

Vitamin Deficiencies • Ascorbic acid C and Toxicities • Niacin B3 • Fat soluble vitamins • Pyridoxine B6 – A, D, E, K • Cobalamin B12 – Deficiency due to abnormal fat • Retinoic acid A absorption • Thiamine B1 – Accumulate and toxicity • B2 • Tocopherol E • Water soluble vitamins • Calciferol D – B1, B2, B3, B6, B12, C, Folate

• Other names, Source

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Vitamin A Deficiency Bitot’s spot Xerophthalmia with corneal ulcer

: night blindness

: Bitot’s spot (small plaques of keratin debris), keratomalacia (corneal ulcer and destruction), xerophthalmia (dry eye), total blindness

: Squamous metaplasia 2o pulmonary , KUB stone (keratin debris)

: vulnerability to infection (measle, , diarrhea)

Corneal scaring Corneal ulcer towards keratomalacia

http://www.cehjournal.org/images/ts040006.jpg

Vitamin D

1, 25 (OH)2 D is the active form of vitamin D (synthesis from kidney by 1-hydroxylase)

Function : stimulate intestinal absorption of Ca and P. : collaborates with PTH in the mobilization of Ca from bone. : stimulate the PTH-dependent reabsorption of Ca in the distal renal tubules

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Rickets

Vitamin D - an excess of unmineralized matrix (osteoid)

Deficiency : (children) - Intramembranous bone formation : (adult) (direct ossification of embryonic connective : Hypocalcemia tetany tissue ; membrane bone of skull) - Endochondral bone formation (Intracartilaginous replacement of hyaline cartilage; bone of trunk and extremities cartilage)

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During nonambulatory stage of infancy: - Head : ศีรษะแบน เปนสี่เหลี่ยม หนาผากนูน (craniotabes, frontal bossing, squared appearance) - Chest : rachitic rosary at costochondral Rachitic rosary junction, pigeon breast deformity, Harrison’s groove.

During ambulatory stage of infancy : Pelvis deformity, lumbar lordosis, bowing legs.

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Pectus excavatum (Funnel chest) Pectus carinatum (Pigeon chest)

http://www.patient.co.uk/doctor/Chest-Deformity.htm http://www.respir.com/images/SemeioPectusExt.jpg http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/9583.jpg

Osteomalacia

- in adult

- Contour of the bone are not affected

- Bone is weak and vulnerable to fracture due to osteopenia

Bowing legs

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Vitamin E (a-tocopheral) : Poor nerve conduction,axon degeneration - serves as a scavenger of free radicals, the on the posterior columns of the spinal antioxidant effect cord, loss of nerve cells in the dorsal - may reduce mutagenesis root ganglia, and degenerative changes in the spinocerebellar tracts - Cause of deficiency : deficient diet is uncommon : occurs in association with : The neurologic manifestations are malabsorption syndromes, infants of low birth ataxia, dysarthria, absent tendon weight, developmental defects in the GI tract, or reflexes, and loss of position sense and lipoprotein disorders. pain sensation.

Vitamin K

Vitamin K Deficiency - Clotting factor 2, 7, 9, 10 : ภาวะเลือดออกงาย (bleeding diathesis) - Anticoagulant protein C and S : Intracranial hemorrhage of the - May favor calcification of bone newborn proteins and inhibit bone resorption  prevent osteoporosis

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Cause of deficiency : Vitamin B1 (thiamine) –fat malabsorption syndromes Function : maintains neural membranes and (biliary tract disease) normal nerve conduction, especially peripheral –destruction of the endogenous nerve : most common in chronic alcoholism, –synthesizing flora (ingestion of result in syndromes of broad-spectrum antibiotics) - dry beriberi (polyneuropathy) –neonatal period - wet beriberi (heart failure, peripheral edema) –Diffuse liver disease - Wernicke – –Drug (e.g., warfarin) (irriversible)

Wernicke – Korsakoff Syndrome

• Lesions in the CNS : hemorrhage and degeneration of mammillarv bodies, periventicular region of thalamus, floor of forth ventricle, anterior region of cerebellum

• is marked by ophthalmoplegia, nystagmus, ataxia of gait and confusion

• Korsakoff psychosis consists of impairment of remote, recall, confabulation, and inability to acquire new information

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Vitamin B2 (Riboflovin)

- cheilosis (cheilitis, angular stomatitis): first + most characteristic sign (crack + fissure at the angles)

- Glossitis : tongue atrophy, red-blue discoloration

- Eye change : interstitial keratitis, corneal vascularization, corneal ulcer

- Scaling dermatitis : nasolabial folds and cheek (butterfly distribution), scrotal, vulva

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Vitamin B3 (Niacin) - an essential component of NAD+ and NADP - (3 D’s): - Dermatitis sharply demarcated scaling and desquamation of exposure area, bilaterally symmetry

- Diarrhea caused by atrophy of the gastrointestinal epithelium

- Dementia results from neuron degeneration in the brain, and in the spinal cord

Vitamin B6 (Pyridoxine) Vitamin B12 (Cobalamin) Deficiency state - Coenzyme in the DNA synthetic pathway - Most common in chronic alcoholism (as well as folic acid) and pregnancy - Vit.B12 + R-binder(saliva)  protease (pancreas) - Clinical findings resemble vit. B2 +  niacin deficiencies (seborrheic dermatitis, vit.B12 + intrinsic factor cheilosis, glossitis, peripheral neuropathy, (gastric parietal cell) convulsion)  absorb at ileum

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Folate

- Coenzyme in the DNA synthetic pathway

- Absorb at proximal jejunum

- Deficiency : clinically some as except neurologic change : Neural tube defects in the developing fetus (first few weeks post- conception) Anencephaly Spina bifida

http://compcolts.wikispaces.com/file/view/spina_bifida.jpg http://www.asylumeclectica.com/asylum/malady/archives/anenceph/anen6.jpg http://www.scienceclarified.com/images/uesc_02_img0090.jpg

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Vitamin C (Ascorbic acid)

-Function : hydroxylation of procollagen, antioxidant

-Deficiency : impaired synthesis of collagen (bone and vessel)

Perifollicular hemorrhage

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Mineral Deficiencies Topics and Toxicities • Nutritional deficiencies • Iron – Protein – Energy Malnutrition – : Iron deficiency anemia – Anorexia Nervosa and Bulimia – Iron excess : Hemochromatosis – Vitamin Deficiencies • Iodine : deficiency : Multinodular goiter – Mineral Deficiencies • Zinc : deficiency : Acrodermatitis • Obesity enteropathica • Diet and Systemic Diseases • Copper : excess : Wilson’s disease

Iron Deficiency : dietary lack, increased requirement, chronic blood loss : koilonychia (spoon nail), alopecia : atrophic changes in the tongue and gastric mucosa, intestinal malabsorption : hypochromic microcytic anemia, poikilocytosis

# Plummer – Vinson syndrome: 1.) microcytic hypochromic anemia 2.) Atrophic glossitis 3.) Esophageal webs (dysphagia)

Hypochromic microcytic anemia with poikilocytosis

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Koilonychia

http://www.topnews.in/files/iodine-deficiency.jpg

Zinc - Acrodermatitis enteropathica, AR ( often around eye, nose, mouth, anus and distal parts) - Anorexia with diarrhea - Growth retardation in children - Impaired wound healing - Hypogonadism - Altered immune function - Impaired night vision - Depressed mental function - Increased incidence of congenital malformations in infants of zinc-deficient mother

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Mineral toxicities

• Hemochromatosis (Fe) : Liver, pancreas • Cirrhosis, DM, cardiac dysfunction • Thalassemia (Fe) • Kayser-Fleischer Ring (Cu) • Hepatolenticular degeneration, brain lesion, Wilson’s disease (Cu)

Acrodermatitis enteropathica

http://www.mayomedicallaboratories.com/articles/hottopics/transcripts/ http://www.eurowilson.com/rc/org/eurowilson/htm/Article/2009/htm- 2009/2009-1a-hemochromatosis/1a-16.html 20090520-075732-571/src/htm_fullText/en/graph_symptomes_ENG.gif

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Topics

• Nutritional deficiencies

?? – Protein – Energy Malnutrition – Anorexia Nervosa and Bulimia – Vitamin Deficiencies – Mineral Deficiencies • Obesity • Diet and Systemic Diseases

Obesity Obesity

Mesurement : Body mass index (BMI) = Wt (kg)/Ht(m) 2 : Body–fat percentage (skin fold measurement) and lean body weight

BMI : normal = 18.5 – 24.9 kg./m2 : overweight = 25.0 – 29.9 kg./m2 : obesity  30.0 kg./m2

http://www.impactlab.com/wp-content/uploads/2008/09/obese3.jpg

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Neurohumoral mechanism

• เปนกลไกการควบคุมการเผาผลาญพลังงาน • Afferent (humoral) signals : leptin(adipose tissue), insulin, ghrelin(stomach)

• Hypothalamus (central melanocortin system)

• Efferent : feeding behavior + energy expenditure (TRH and autonomic pathway)

Factors contributing to Food–derived energy > energy expenditure obesity :

1. Genetic predisposition Storage as triglycerides in adipose tissue (insulin effect) 2. Decreased lipid utitization : aging, defective thermogenesis, inactivity, - Daily requirement : 2000 – 3000 kcal/d. underexcercising - Daily energy expenditure = Basal energy expenditure (BEE) 3. Sociocultural environment : stress, +Activities. emotional, disturbances 4. Diseases : hypothalamic disorder. BEE man = 66 + (13.7 x Wt.) + (5 x Ht.) – (6.8 x age) : hypothyroidism. BEE woman = 655 + (9.5 x Wt.) + (1.8 x Ht.) – (4.7 x age) Wt (Kg), Ht (cm.), Age (yrs) : Cushing’s syndrome. : Polycystic ovary syndrome.

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Exercise more than 3 times per week

1. Aerobic exercise = moderate intensity + long duration (20 – 45 min.)  use oxegen to burn fat  Cardiovascular protection

2. Anaerobic exercise = high intensity + short duration.  glycogenolysis + muscular hypertrophy

Diet and systemic diseases Topics • Fiber   cholesterol level • Nutritional deficiencies   diverticulosis, CA colon – Protein – Energy Malnutrition • Fish oil  omega–3 FA   cholesterol and – Anorexia Nervosa and Bulimia coronary heart disease – Vitamin Deficiencies • Restricted Na intake   HT – Mineral Deficiencies • Restricted protein diet in liver disease and • Obesity chronic renal failure • Diet and Systemic Diseases

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ขอมูลเพิ่มเติม References • สํานักงานกองทุนสนับสนุนการสรางเสริมสุขภาพ • สุภรณ พงศะบุตร, บรรณาธิการ, “ตําราพยาธิวิทยาทั่วไป.”, ภาควิชา http://www.thaihealth.or.th/about พยาธิวิทยาและนิติเวชศาสตร, โกลบอลพริ้นท, 2551, หนา 417- • โครงการคนไทยไรพุง กรมอนามัย กระทรวงสาธารณสุข 438. http://nutrition.anamai.moph.go.th/web /khonthairaipung.html • Kumar V., Abbas A. K., Fausto N., • สํานักโภชนาการ กรมอนามัย กระทรวงสาธารณสุข “Robbins and Cotran Pathologic Basis http://nutrition.anamai.moph.go.th/ of Disease, 7th edition.”, Elsevier Saunders, 2005, p.446-466.

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