Biochem Basics 3 - Nutritional Diseases

malabsorption can result from defects in what phases of nutrient absorption?

- luminal processing

- absorption into the intestinal mucosa (mucosal absorptive phase)

- transport into the circulation (postabsorptive, processing phase)

luminal phase

a. substrate hydrolysis

b. fat solubilization

c. luminal availability of specific nutrients

mucosal absorptive phase

a. brush border hydrolysis

b. epithelial transport

postabsorptive, processing phase

a. enterocyte processing

b. lymphatic

lipid malabsorption

- Steatorrhea

disturbances in lipid digestion and absorption

- cystic fibrosis: thickened secretions - enzyme can not reach the intestine

- orlistate: inhibitor of gastric and pancreatic lipases

pancreatic insufficiency

- lipid malabsorption

- malab of fat and fat-soluble vitamins (ADEK)

Abeta-Lipoproteinemia

- lipid malabsorption

- apoB def (defect in chylomicron synthesis)

celiac sprue

- carb malab

- reaction to gluten

Disaccharidase deficiency

- carb malab

- ex. lactase def

Fat malabsorption and steatorrhea may result from disorders of?

- bile acid metabolism or bile secretion

- impaired production

- activity of pancreatic lipase or colipase (e.g., pancreatic

insufficiency)

- transport into the circulation (e.g., abetalipoproteinemia)

Impaired absorption of carbohydrates may result from a?

- deficiency in pancreatic amylase

- reduced disaccharidase activity (e.g., disaccharidase deficiency)

- decreased absorptive intestinal surface area (e.g., Celiac sprue)

Impaired digestion and absorption of dietary protein occurs when?

- pancreatic protease secretion and/or activity is impaired

(chronic pancreatitis or cystic fibrosis).

- Protein malabsorption can also occur in diseases with reduced intestinal absorptive surface.

incomplete proteins

- lack an essential AA

- will not support life

pellagra

- multiple nutrient deficiencies

- Niacin (and tryptophan) deficiency

- 3 D's (dermatitis, diarrhea and dementia)

- kynurenine pathway

- diet with incomplete proteins (corn or milling)

- chronic alcoholics

PEM is associated with one of two classical syndromes depending on presence or absence of ____, which are?

edema:

- marasmus (without edema; wasting syndrome)

- kwashiorkor (with edema)

- with manifestations of both (mixed marasmus-kwashiorkor).

marasmus

- (PEM without edema)

• Overall malnutrition (Protein and calorie)

• Affects a few compartments:

• Skeletal muscle (somatic compartment; wasting) and body fat stores (depletion) - more severe than Kwashorkor

• Liver (protein storage/visceral compartment)- less severe than Kwashiorkor

• Most common world wide (Up to 25% of children)

• U.S. - neglected infants or secondary to other diseases

- loose skin, cachectic appearance, tissue and muscle wasting

Kwashiorkor

(PEM with edema)

• Protein deprivation (adequate in calories)

• Marked muscle atrophy with normal or increased body fat.

• Severely affected protein stores (primarily in liver)

• Reduced regeneration of intestinal epithelial cells---makes

malabsorption worse.

• Common form:

- Early weaning and diets (low in protein)-- Africa

- Also high in impoverished Southeast Asia

- Mild form-- Chronic diarrhea/chronic protein loss- US

Mixed marasmus-kwashiorkor

(edematous malnutrition)

— may occur in a child who has inadequate dietary intake of all nutrients and is triggered by a common infectious illness of childhood

Kwashiorkor symptoms

- early weaning

- swolen belly

- non-pigmented hair

- skin lesions

MEAL - malnutrition, Edema, Anemia, Liver

Anorexia Nervosa

- Self-induced starvation

- Clinical symptoms similar to PEM

- Amenorrhea (absence of menstruation; reduced gonadotropin-releasing hormone) is common

- Refuse to eat, Symptom similar to protein malnutrition (PEM)

Bulimia

- more common than anorexia

- Binge eating (or overeating), then induce vomiting

- Amenorrhea is less common (fewer than 50%)

Protein-energy malnutrition (PEM) can be divided into the?

clinical subtypes depending on the presence or absence of edema.

Marasmus is characterized by the?

(PEM without edema), wasting of muscle mass and the depletion of body fat stores. It is the most common form.

Kwashiorkor is characterized by?

(PEM with edema), marked muscle atrophy with normal or increased body fat. Presence of edema for diagnosis.

Acute malnutrition typically causes _____, while chronic malnutrition causes _____?

wasting (with reduced weight/height); stunting (with reduced height for age).

Malnourished children usually have deficiencies of?

- specific micronutrients, particularly vitamins A and D, folate, and iron.

- In addition, they are deficient in one or more nutrients required for growth, including protein, electrolytes, and

zinc.

- These deficiencies are treated empirically during nutritional rehabilitation.

secondary PEM includes?

cachexia seen in advanced cancer (may appear before loss of appetite)

Behavior induced malnutrition includes?

anorexia nervosa (similar to severe PEM) and Bulimia (less severe).

etiology of energy balance

• Disorder of energy balance

- Intake and expenditure

- Regulated by neurons and hormones

lipostat

• Lipostat (sensor of energy balance)

- Energy stores (adipose tissue)

- Food intake

- Energy use

- Obesity genes---leptin

leptin

obesity gene that acts on hypothalamus

what occurs in the absence of food intake?

short term:

• Ghrelin -> Hypothalamus

- Appetite increased

- Energy expen reduced

• Ins, Leptin, CCK, PYY reduced.

what occurs during a meal?

short-term

• Ins, Leptin, CCK, PYY

• Hypothalamus

- Appetite reduced

- Energy expend increased

BMI

body mass index, weight in kg/[height in m]^2

BMI ranges

underweight:

metabolic syndrome

- low HDL

- high TG

- glucose intolerance

- insulin resistance

- hypertension

type 2 diabetes

• > 80% due to excess weight

• incidence increased 30 % in last 10-15 years (along with obesity)

• > child obese--adolescents (not "maturity onset")

highest incidence of diabetes in the world

pima indians

tropical sprue

Probably infectious. Similar to celiac sprue but can affect entire small bowel

whipple's disease

Infection with gram positive, Tropheryma whippeli