Lec11 Nutritional Pathology Flashcards
What is most prevalent nutritional disorder in US
obesity
Definition obestity
accumulation adipose tissue that imparis health
BMI? Whats normal? overweight? obese?
weight [kg]/ (height in meters )^2
normal: 18.5-25
overweight: 25-30
obesity: >30
Is central [visceral] or subcutaneous fat more dangerous?
central adipose tissue accumulation associated with higher risk for many diseases
What are main measures of body fat?
- waist and hip circumference ratio
- skinfold thickness
- mid-upper arm circumference
What is normal wasit-hip circumference ratio?
obesity = >0.8-0.85 for women
= >0.9-1.0 for men
What is steatosis
increased fat
- may resolve or may progress to steatohepatitis
What is oil red o stain?
- stain for fat
- use for steatosis
What is steatohepatitis?
- steatosis of liver wtih inflammation
- leads to: fibrosis, cirrhosis, hepatocellular carcinoma
- can be due to alcohol or metabolic stuff
What is a mechanical effect of obesity?
osteoarthritis
What are 8 major pathologic complications of obesity
- type II diabetes
- hypertenesion
- hypertriglycidemia and low HDL
- non-alcoholic steatoehpatitis
- osteoarthritis
- heart disease/atherosclerotsis
- increased risk of cancer
- respiratory stuff [sleep apnea, hypoventilation]
Cause of obesity
imbalance of caloric intake and energy expenditure complicated by:
- genetic
- neural
- hormonal
- psychological
- nutritional
- environmental
Adipocytes - what do they secrete?
- number of adipocytes set in childhood/adolescence
- secrete
- leptin
- adiponectin
- TNF, IL6, IL1, IL18
What is leptin? Effect of disruption leptin signalling?
- secreted by adipocytes and go to receptors in brain
- signals adequacy of fat stores
- decrease appetite/food intake [anorexigenic effect]
- downregulates path that increases appetite and upregulates path that increases energy expenditure
- disruption of signaling –> overeating and weight gain
What is ghrelin?
- produced in stomach
- increases food intake
- ghrelin levels rise before eating and fall 1-2 hrs after eating
- in obese people: grhelin levels always remain high
What is peptide YY [PYY]?
- secreted by endocrine cells in ileum/colon
- levels of PYY low during fasting and increase during food intake
- cause reduction in food intake/appetite [anorexigenic]
Adiponectin
- secreted by adipocytes
- directs fat to muscle and away from liver
- decreases glucose production in liver
- lower levels of adiponectin in obese individuals
How is obesity an inflammatory state
- obesity leads to high C reactive protien that is a marker of inflammatory activity
What medications for managing obesity?
- meds that decrease appetite: noradrenergic, serotoninergic
- meds that partition fats, prevent fats being absorbed by GI tract
What surgical methods for managing obesity
roux-en-Y: bypass stomach
sleeve gastrectomy: stomach staple to make smaller
gastric banding: make stomach smaller
what is primary vs secondary protein/energy malnutrtion
primary: food unavailable
secondary: secondary to coexisting disease
Who does primary protein energy malnutrition effect?
- children in poor countries
- elderly isolated in US with inaccessibility of food
Marasmus
- global starvation
- wasting appearance: loss of fat/muscle especially in extremities, growth retardation
- vit and immune deficiency
- age <1 year
- normal serum albumin
- patients are alert
Kwashiorkor
- protein deficiency even though adequate calories
- occurs when child is switched from milk to predominantly carbohydrate diet
- edema [low oncotic pressure]
- fatty liver [low lipoproteins that are needed to transport fat out of liver]
- skin lesions
- hair hypopigmentation
- vit and immune deficiency
- age > 1 year
- low serum albumin
- patients are listless
Secondary causes of protein energy malnutrtition
- acute infection [ increases metabolic rate]
- chronic diseases: cancer, HIV, anorexia, bulimia, malabsorption, alcoholism
What is cachexia?
- extreme weight loss, fatigue, muscle atrophy, anemia, anorexia
- in cancer and HIV patients
- secondary to atrophy of diaphragm and respiratory muscles in cancer patients
Which proteins involved in cachexia?
- PIF [proteolysis inducing factor]
- LMF [lipid-mobilizing factor]
- cytokines [TNF-a, IL6]
What is proteolysis inducing factor [PIF]?
- secreted in urine of patients with pancreatic cancer and cachexia
- may play role in cachexia
What cytokines play a role in cachexia?
- TNF-a or IL-6
- may be secreted by tumor or in response to tumor
What is lipid mobilizing factor [LMF]
- increases fatty acid oxidation
- increases pro-inflammatory cytokines
- may play role in cachexia
What is anorexia nervosa?
eating disorder characterized by excessive weight loss, food restriction, distorted body self immage
What is anorexia?
decreased appetite/food intake, not the same as the eating disorder
What is bulimia?
bing eating usually followed by induced vommiting
What is bulimia nervosa?
eating disorder characterized by binge eating followed by induced vomiting
Which vitamins are fat soluble?
- vit A, D, E, K
- can accumulate to toxic levels
- fat malabsorption syndrome can lead to low levels
Which vitamins are water soluble?
- B and C vit
- rarely toxic
Are water or fat soluble vit more likely toxic?
fat soluble
What is vitamin A
- group of related compounds
- retinol, retinal, retinoic acid
What are retinoids?
- vitamin A and other compounds with similar structure
- may or may not have vit A effects
Sources of vitamin A?
caratenoids [B carotene]
- provitamins that are converted to vit A
- found in yellow and leafy veggies [carrots]
preformed vit A in animal derived food [eggs, fish, liver, milk, butter]
Functions vitamin A
- helps vision, cell differentiation, growth, metabolism, resistance to infection
- mostly focus on: VISION, CELLULAR DIFFERENTIATION
Effects of vitamin A deficiency?
- blindness
- immune deficiency
- squamous metaplasia
- – in lacrimal glands –> get dry eyes and conjunctiva
- – respiratory tract –> get pulmonary infections more easily
- – urinary tract –> get kidney and urinary stones
Effects of squamous metaplasia in vit A deficiency [3 places]
in lacrimal glands –> get dry eyes and conjunctiva
respiratory tract –> get pulmonary infections more easily
urinary tract –> get kidney and urinary stones
What is cause and effect of vitamin A toxicity? Acute vs chronic?
- overuse of dietary supplements, or lots of liver in diet [which has lots of vit A]
- acute toxicity: headache, dizziness, vomitting, blurred vision
- chronic: weight loss, anorexia, nausea, vomitting, enlarged liver
Therapeutic uses of vit A?
- retinoids to treat acne, psoriasis, acute promyelocytic leukemia
- retinoic acid and preformed vit A are also teratogens
What is vitamin C?
- ascorbic acid
- plays role in biosynthetic paths [COLLAGEN SYNTHESIS
- antioxidant
- in citrus fruits, veggies, milk, fish, liver
Effect of vitamin C deficiency?
- scurvy, get poorly formed collagen and thus:
- bleeding [due to weak blood vessel walls]
- – hemorrhages, swollen and bleeding gums
- bone pain
- poor wound healing
Why is vitamin C toxic or not toxic?
not toxic because:
- water soluble
- unstable
- poorly absorbed in intestine
Source of vit D
- 90% from photoconversion of precursor in skin
- 10% from diet: fish, plants, grains
- needs to be converted by liver and kidney before active effect
- acts on osteoclasts/blasts, intestine absorption, kidney itself
Function of vit D
CALCIUM REGULATION - stimulates intestinal Ca reabsorption - stimulates renal Ca reabsorption - interacts with parathyroid hormone - induces mineralization of bone also [less importantly] regulation of: - immune system, cell proliferation, cell differentiation, apoptosis, angiogenesis
Cause of vit D deficiency
- inadequate vit D in diet
- fat malabsorption syndrome
- limited sunlight exposure
- abnormal conversion to active form [due to liver or kidney disease]
3 diseases associated with vit D deficiency
- rickets [ in kids]
- osteomalacia [in adults]
- hypocalcemic tetany [muscle problem]
what is rickets?
- vit D deficiency in kids
- inappropriate endochondral bone formation
- get bowing in legs
Effect of vit D toxicity
- get high Ca, Ca deposition in soft tissue [metastatic calcification]
- bone pain and hypercalcemia
General function of B vitamins?
usually cofactors
General function of vit E?
antioxidants
General function of vit K?
important for clotting factors
How to tell marasmus vs kwashiorkor
marasmus: 1 yr old, edematous, low serum albumin, patient is listless
