Part 7 Flashcards
Starvation definition
physiological condition created in the body as a consequence of chronic insufficient food intake
Physiological: adaptive to promote survival
Pathological: adaptation is compromised
Ethical barriers to studying malnutrition
Obligation to do no harm - must treat rather than observe
- offer best standard of care as the control
Double-blind randomized controlled clinical trials
- drug trials but no malnutrition
Malnutrition is often multi-nutrient, no biomarkers for mild deficiency, subclinical infections
Zinc deficiency can be mistaken for PEM
Ancel Keys 1950’s experiments on starvation
What they did, body composition changes and metabolic flux after 6 months
1500 kcal per day and 50g protein per day for 6 months (low energy and low protein)
~23% weight loss, ~24% lean tissue loss, ~71% fat loss, 4% increase in extracellular fluid
Rate of lean tissue and fat loss was 0 after 6 months (successful adaptation and stable body comp)
Metabolic response to starvation from Ancel Keys 1950 experiment
Reduced resting energy expenditure:
- reduced per unit of tissue within days
- reduced mass of metabolically active tissue within weeks
- reduced heart rate and muscle tone
Reduced non-resting energy expenditure:
- reduced work of movement with lower body weight
- reduced voluntary movement
Reduced protein requirement:
- diminished lean tissue
- increased retention of dietary protein
- stabilization of lean tissue mass (0 rate of change)
Cellular regulation in starvation Gcn2
↑ Gcn2 = general control nonderepressible 2 (protein kinase) - protein synthesis regulation
1) inhibits general translation by phosphorylation of elF-2alpha
2) binds uncharged tRNA
3) general inhibition of translation
4) down-regulates genes regulating fatty acid and triglyceride synthesis through SREBP-1c
5) delays entry into S phase of cell cycle
Overall inhibition of anabolism
Cellular regulation in starvation AMPK
AMPK = 5’ AMP-activated protein kinase
1) Senses high [AMP], energy charge of cell
2) inhibits mTORC1
3) ↓ protein synthesis
4) ↓ genes regulating fatty acid and triglyceride synthesis via SREBP-1c
Definition of successful adaptation (physiological)
Accomplished through: Making physiological changes to reduce energy and protein requirement for homeostasis
Benefit: survival
Cost: lean tissue loss, fatigue and inactivity, immunodeficiency, reduced stress tolerance, irritability
Clinical features of PEM
- reduced body weight
- muscle wasting
- reduced respiratory and cardiac muscular capacity
- skin thinning
- ↓ metabolic rate
- hypothermia
- apathy
- edema
- immunodeficiency
Pathophysiology of PEM
Adaptive mechanisms: reduce protein stores, reduce metabolic rate
- hypotension, bradycardia (slow HR), hypothermia
Successful adaptation: 0 protein/energy balance, normal serum albumin
Failed adaptation: continued protein/fat loss, hypoalbuminemia, immune deficiency
- can be following any additional stressors including metabolic stress, micronutrient deficiency or too severe starvation
Dutch famine
Dutch famine birth cohort study
1944-1945 sudden onset famine in German-occupied Netherlands due to cut off from food and fuel shipments
- 4.5 million affected, 22,000 died
- Pregnant women heavily affected, studies done following babies in utero at the time later
Study:
- intrauterine restricted growth (IUGR)
- ↑ chronic diseases, their own infants were IUGR, Barker hypothesis epigenetic changes
First 1000 days
1) A nutritious diet for pregnant mothers
2) Good care for pregnant mothers
3) 6 months exclusive breast feeding
4) Nurturing, responsive care of babies and toddlers
5) Good food introduction timing
6) Healthy and nutritious diet for babies and toddlers
7) Paid time off for working parents
8) Education for parents and caregivers
9) Consistent access to nutritious food for young children
10) Societal investments in well-being of babies/toddlers
Edematous undernutrition
Considered a non-successful adaptation
Fluid leaking from capillaries pools
Lowered muscle tone leads to inability to circulate blood
Pitting edema
Common infections with undernourished patients
Diarrhea
Pneumonia
UTI
Measles
Tuberculosis
Parasitic infections - worsen anemia and GI infections
Symptoms: ↓ antibodies, ↓ hemoglobin (anemia), dysentery, fever, fluid imbalances (heart failure and death)
Medical nutrition therapy for undernourished patients
1) restore fluid/electrolyte imbalances
2) cautious nutrition intervention, slow protein ↑
3) treat infections
4) Involve local communities
What causes unsuccessful adaptation to malnutrition?
Add a micronutrient deficiency or a stress or surgery
Including: cancer, trauma, inflammation/infection
- increases energy expenditure/requirements and nitrogen output (catabolism)
