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Pathobio Exam 1
Set 7: Nutritional Diseases
176
Pathology
Graduate
10/09/2011

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Term
What 3 things should all adequate diets provide?
Definition
1) energy (carbs, fats, protein)
2) aa & FA (essential & non-essential)
3) vitamins/minerals
Term
def

primary malnutrition
Definition
deficiency due to intake
Term
def

secondary malnutrition
Definition
deficiency due to inadequate absorption, impaired usage/storage, excess loss, increased need
Term
def

malnutrition
Definition
deficiency or inadequacy of any or all nutrients needed in an adequate diet
Term
Fuction

Vitamins
Definition
act as co-enzymes or hormones in vital metabolic pathways
Term
What are the 2 categories of vitamins?
Definition
Fat Soluble
Water Soluble
Term
What are the fat soluble vitamins?
Definition
A, D, E, K
Term
What are the water soluble vitamins?
Definition
B family, C
Term
What is required for dietary absorption of FS vitamins?
Definition
effective pancreatic & biliary function for dietary absorption
Term
What usually causes FS vitamin deficiency?
Definition
disturbances of fat absorption
Term
What causes WS vitamin deficiency?
Definition
primary or seconday malnutrition
Term
Are FS or WS vitamins found to have higher body stores?
Definition
FS
Term
def

Vitamin A
Definition
carotene family, retinal group
Term
What are the 4 normal functions of Vit A?
Definition
1) component of visual pigment rhodopsin: retinal
2) maintain specialized epithelial differentiation (affects transcription of genes thru interation with DNA)
3) effects metabolism, inc. FA
4) resistance to infection & stimulation of immune system
Term
What are the dietary sources of Vit A?
Definition
1) animal-derived products (fish, eggs, milk - retinol)
2) leafy green/yellow vegetables (carotenoids, β-carotene)
Term
Where is 90% of Vit A stored in the body?
Definition
liver
Term
What is the storage form of Vit A?
Definition
Retinol
Term
What is the visual pigment form of Vit A?
Definition
Retinal
Term
Sx

Vit A Deficiency
Definition
1) nyctalopia (night blindness)
2) squamous metaplasia & keratinization
a) eye: xerophtalmia (dry eye), keratomalacia (corneal ulceration), corneal clouding
b) skin & other epithelia: follicular hyperkeratosis
3) susceptibility to inf. (esp. measles)
4) predisposition to neoplasia (via squamous metaplasia)
Term
What causes nyctalopia in Vit A deficiency?
Definition
decreased rhodopsin in retinal rods & cones
Term
def

Vitamin D
Definition
calciferol family
Term
What is the normal function of Vit D?
Definition
maintain plasma calcium & phasphate levels for adequate bone mineralization
Term
What are the sources of Vit D?
Definition
dietary: meat, dairy, additives (D2) conversion: via UV light to D3
Term
Where does Vit D travel to, once absorbed the gut or converted via UV?
Definition
Blood (has D-binding protein transporter) => liver
Term
What metabolism of Vit D occurs in the liver?
Definition
hydroxylation via 25-hydroxylase => 25-OH-D
Term
Where does 25-OH-D go once leaving the liver?
Definition
kidney
Term
What metabolism of 25-OH-D occurs in the kidney?
Definition
hydroxylation by 1-hydroxylase => 1,25(OH)2D
Term
What is the active form of Vit D?
Definition
1,25(OH)2D
Term
How does 1,25(OH)2D facilitate calcium & phosphate aborption in sm. bowel?
Definition
activating synthesis of calcium-binding proteins
Term
What are the possible Vit D deficency causes?
Definition
1) malnutrition
2) malabsorption
3) chronic underexposure to sunlight
4) chronic liver diesaes
5) chronic renal disease
6) induction of CYP450
7) defective hydroxylase enzymes
Term
What diease is seen in Vit D deficiency in children?
Definition
Rickets
Term
What disease is seen in adults with Vit D deficency?
Definition
osteomalacia
Term
Sx

Rickets
Definition
- bowing deformities of wt-bearing long bones & spine
- overgrowth of cartilage at apiphyseal plates & ribs (rachitic rosary)
- other deformities
Term
Sx

osteomalacia
Definition
- decreaed bone density on radiographs
- osteoid excess
- minimal deformity
- susceptibility to microfractures
Term
def

osteoporosis
Definition
bone is mineralized, but composed of thinner trabeculae
Term
Sx

Osteoporosis
Definition
bone density loss => wt-bearing areas brittle & susceptible to fracture (esp. hips & vertebral bodies)
Term
def

Vitamin K
Definition
menaquinone family
Term
Function

Vit K
Definition
cofactor for carboxylation rxns important in blood clotting
Term
What are the sources of Vit K?
Definition
dietary: green, leafy vegetables
other: intestinal bacteria synthesis
Term
Function

carboxylase Vit K is a cofactor for
Definition
converts glutamyl residues to γ-carboxyglutamates (provides calcium-binding sites)
Term
Effect

carboxylase + Vit K cofactor
Definition
Allows interaction b/w clotting factors II, VII, IX, X (prothrombin family) & phospholipid surface necessary to generate thrombin
Term
What inactive form of Vit K is formed after use?
Definition
Vit K epoxide
Term
How is Vit K epoxide recycled to active Vit K?
Definition
hepatic reductase
Term
How does Warfarin affect the Vit K cycle?
Definition
inhibits recycling of Vit K epoxide
Term
Why are Vit K deficencies rare?
Definition
1) efficient recycling
2) interstinal flora provide ongoing source
Term
Sx

Vit K deficency
Definition
bleeding diathesis (=> hematoma, hematuria, melena, eccymoses, gingival bleeding, etc)
Term
What can cause Vit K deficency?
Definition
1) neonates - absence of gut flora
2) diffuse liver disease - fat malabsorption
3) Abx - destruction of normal flora
4) warfarin therapy - inhibition of hepatic reductase
Term
def

Vitamin E
Definition
α-tocopherol
Term
What is the dietary source of Vit E?
Definition
vegetable oils
Term
Function

Vit E
Definition
anti-oxidant: inhibit formation of oxygen radicals
Term
Structure

Vit E
Definition
phenol-like aromatic head attached to saturated hydrocarbon tail (allows molecule to "sit" in membrane lipid layers)
Term
How does Vit E protect from oxidation by free radicals?
Definition
Vit E is readily oxidized (takes lipid membrane place => protection)
Term
Why is it important to protect membranes from lipid peroxidation?
Definition
it's an autocatalytic charin rxn => single oxidation could propagate throughout the membrane
Term
Why is Vit E deficency rare?
Definition
efficient recycling
Term
When can Vit E deficency occur?
Definition
1) severe fat malabsorption
2) premature infants => low levels at birth combined with oxidative stress s.a. oxygen therapy
Term
Sx

Vit E deficency
Definition
1) spinocerebellar degeneration
2) hemolytic anemia (esp. newborns)
3) increased susceptibility to ischemic heart disease
Term
What are the general properites of water soluble vitamins?
Definition
1) sm. organic molecules
2) required in sm. amounts
3) used in universal energy utilization pathways
4) limited body stores easily depleted
5) deficency => systemic syndrome
Term
def

Vitamin B1
Definition
Thiamine
Term
What are the sources of thiamine?
Definition
1) widely in nature (not in refined foods)
2) low intracellular reserves (muscle, heart & brain)
Term
Function

thiamine
Definition
rxns where aldehyde groups are transferred
1) ATP sunthesis
2) pentose phosphate pathway
3) maintenance of normal nerve membranes/conduction
Term
Where in the world is thiamine primary malnutrition of thiamine common?
Definition
underdeveloped countries where diet consiss of processsed food
Term
What is the main source of thiamine defiency?
Definition
chronic alcoholism - inadequate diet or tansketolast abnormality
Term
What in thiamine deficiency affects cerebral function?
Definition
impiared glucose metabloism
Term
What in thiamine deficency impairs myocardial function?
Definition
abnormal ATP synthesis
Term
What 2 myocardial syndromes are seen in thiamine deficency?
Definition
Dry Beri-beri
Wet Beri-beri
Term
What 2 cerebral syndromes are seen in thiamine deficency?
Definition
Wenicke & Korsakoff's syndromes
Term
Sx

Wet Beri-Beri
Definition
myocardial failure with edema & vasodilation
Term
Sx

Dry Beri-Beri
Definition
peripheral neuropathy affecting lower extremities more than upper
affects motor, senory & reflex function
Term
def

"beri"
Definition
weakness
Term
Sx

Wernicke's encephalopathy
Definition
eye movement abnormalities (nystagmus, ophthalmoplegia)
dysarthria
confusion
ataxia
Term
Sx

Korsakoff's psychosis
Definition
retrograde amnesia
anterograde amnesia
confabulation
Term
What is the pathology of Wernicke & Korsakoff?
Definition
acute hemorrhagic necrosis of mammillary bodies & periventricular gray matter => atrophy
Term
deb

Vitamin B3
Definition
Niacin
Term
def

Vitamin B2
Definition
Riboflavin
Term
def

Vitamin B6
Definition
Pyridoxine
Term
Why are deficencies of riboflavin, pyridoxine, & niacin rare?
Definition
widely present in common food sources
Term
Function

Riboflavin
Definition
Co-factor in energy pathways (FMN, FAD)
Term
Function

Pyridoxine
Definition
cofactor in transamination/decarboxylation rxns
needed for neurotranmitter systhsis and other synthetic pathways
Term
Function

Niacin
Definition
Co-factor in energy pathways (NAD/NADP)
Term
How do B2, B3, & B6 deficiencies manifest?
Definition
In organs with rapid turnover/active metabolism => abnormalities
Term
Sx

B2, B3, B6 Deficiencies
Definition
Epithelium (dermatitis, glossitis)
Bone marrow (anemia)
neural tissues (neuropathy, dementia)
Term
def

pellagra
Definition
clinical syndrome of dermatitis, diarrhea, dementia from niacin deficency
Term
What is the first & most chariacteristic Sx of riboflavin deficency?
Definition
cheilosis (cracks & fissures @ edge of mouth)
Term
def

Vitamin C
Definition
ascorbic acid
Term
What are the sources of Vit C?
Definition
dietary: fresh leafy vegetables, tomatoes, citrus fruit
body store: depleted in 30-40 d without intake
Term
Function

Vit C
Definition
1) anti-oxidant/free radical scavenger
2) biosynthesis
3) immune function
4) collagen cross-linking
Term
What happens to excess Vit C intake?
Definition
excreted in urine
Term
What disease is seen in Vit C deficency?
Definition
scurvy
Term
Sx

Scurvy
Definition
1) bleeding tendency
2) slow/inadequate wound healing
3) children: skeletal changes (Moeller-Barlow disease: compare to rickets)
4) dermatologic change & frequent gingival/periodontal inf.
Term
def

Vitamin B9
Definition
folate (THF)
Term
def

Vitamin B12
Definition
cobalamin
Term
Function

B12 as a cofactor
Definition
1) help enzyme generate FH4 (THF) from it's methylated form 2) aids conversion of methylmalonyl CoA ro succinyl CoA
Term
What is THF a co-enzyme for?
Definition
thymidylate synthetase (required for DNA precursor generation)
Term
What happens to THF in B12 deficency?
Definition
trapped in methylated form => THF deficency
Term
What happens when the succinyl pathway is interrupted by B12 deficency?
Definition
accumulation of methylmalonate & propionate => abnormal FA formation => membrane damage
Term
What is the Vit B12 source
Definition
animal food sources only
Term
Why are primary B12 decfiencies rare (except in vegans/macrobiotic diets)?
Definition
storage reserves last for years
Term
What is the main source of B12 defiency?
Definition
malabsorption since the B12 absorption pathway is complex
Term
def

Pernicious anemia
Definition
autoimmune diease resulting from production of auto-Ab to IF or gastric parietal cells (they synthesize & secrete IF)
Term
Sx

pernicious anemia
Definition
chronic inflammation of gastric lining epithelium => gastric gland atrophy, achlorhydria & intential metaplasia w/ atrophic glossitis
Term
What is the source of folate?
Definition
green vegetables, fruit, animal proteins
Term
What type of folate decifency is common?

Why?
Definition
secondary due to increased requirement resulting from increased DNA synthesis
1) pregnancy
2) infancy
3) hemolytic anemias

(or B12 deficency => B9 deficency)
Term
What drugs can inhibit folate absorption?
Definition
Oral contrsceptives
Phenytoin
Term
What drugs can inhibit folate metabolism?
Definition
anti-neoplastic drugs
Term
What causes megaloblastic anemia?
Definition
insufficent B12/folate due to impaired DNA synthesis
Term
What happens to hematopoiesis in megaloblastic anemia?
Definition
nuclear-cytoplasmic dystrophy wtih immature nuclei lagging behind maturation => clinically ineffective hematopieosis
Term
What happens to RBCs & neutrophils in megaloblastic anemia?
Definition
1) enlarged ovioid RBCs
2) hypersegmented neutrophils
Term
def

subacute combined degeneration
Definition
Severe B12 deficency where myelin degeneration develops in posterior & lateral funiculi of SC
Term
Sx

Subacute combined degeneration
Definition
spastic paraparesis
sensory loss
painful paresethsias (itching, burning)
Term
What can happen in severe B12 deficency when treated with folate?
Definition
anemia response
no neurological response
Term
def

trace metals
Definition
minerals occuring at concentration <1 mg/gm
Term
What 3 things in the body is iron essential to the function of?
Definition
1) hemoglobin
2) myoglobin
3) enzymes
~ 75% of all body iron is in these processes
Term
Why is iron absorption & storage availability tightly regulated?
Definition
1) potential cellular toxicity
2) sequestered from pathogenic orgs
3) limited ability to dispose of increased stores
Term
What is the storage form of iron that's immediately accessible?
Definition
ferritin
Term
def

hermosiderin
Definition
iron aggregates without protein shell stored in lysosomes
Term
Where is iron absorption controlled?
Definition
intenstinal muscosa
Term
What does the liver secrete to inhibit the transfer of iron from mucosal cells to the plasma?
Definition
hepcidin
Term
How much of dietary iron is actually absorbed per day?
Definition
10-15%
Term
What mediates iron transport in the blood?
Definition
transferrin => delivers to RBC precursors
Term
What happens to unused iron stores not transferred to the blood?
Definition
sloughed off
Term
def

total iron binding capacity
Definition
potential serum iron level if all transferrin binding sites are completely occupied (usually ~1/3 TIBC)
Term
What can cause iron deficency?
Definition
1) inadequate diet
2) infants/children (increased need, low dietary content)
3) chronic blood loss
4) impaired absorption
Term
What happens in iron deficency due to decreased heme synthesis?
Definition
microcytic-hypochromatic anemia
Term
What occurs in iron deficency due to decreased iron containing enzymes?
Definition
1) nail changes
2) atrophic glossitis
3) esophageal webs
Term
What is Plummer-Vinson syndrome in iron deficency?
Definition
atrophic glossitis + esophageal webs + anemia
Term
Dx

iron deficency
Definition
1) decreased serum ferritin
2) decreased bone marrow hemosiderin on biopsy
3) increased TIBC (due to increased transferrin)
4) decreased transferrin saturation
Term
Sx

Zinc deficency
Definition
growth/wound healing
Term
Sx

Copper deficency
Definition
anemia & collagen defects
Term
Sx

selenium deficency
Definition
chronic pain, cardiac disease
Term
def

fluoride deficency
Definition
susceptibility to tooth decay
Term
Sx

iodine deficency
Definition
goiter
hypothyroidism
Term
def

goiter
Definition
enlargement of thyroid
Term
How does iodine deficency cause goiter?
Definition
iodine deficency + inadequate production of thyroid hormone => TSH secretion => enlargement
Term
Sx

hypothyroidism
Definition
impaired neurological development(cretinism)
myxedema (diffuse edema with slowing of mental/physical function)
Term
What can cause hypothyroidism besides iodine deficency?
Definition
disturbance in thyroid, pituitary, or hypothalamous
Term
What vitamins can be toxic?
Definition
FS vitamins
Term
Sx

Vitamin A toxicity
Definition
1) teraogenesis
2) hepatic dysfunction
3) increased ICP (children)
4) if consume too many vegetables with β-carotene => non-toxic yellow skin
Term
Sx

Vit B6 Toxicity
Definition
peripheral neuropathy
Term
Sx

Vit D toxicity
Definition
hypercalciruia => nephrolithiasis & metastatic calcifications
Term
What can cause iron toxicity?
Definition
Diet
Increased RBS turnover
genetic disease
repeated blood transfusions
Term
Sx

iron toxicity
Definition
hemosiderosis (localized or systemic)
hemochromatosis (acquired or inherited)
Term
Where is protein-energy malnutrition seen?
Definition
famine/war-torn areas
severely ill
Term
What are the 2 primary forms of protein-energy malnutrition?
Definition
1) marasmus
2) kwashiorkor
Term
What are the 2 components of body protein?
Definition
1) somatic (skeletal muscle)
2) visceral (organ stores)
Term
What comparentment of preotein is depleted in marasmus?

kwashiorkor?
Definition
m: somatic
k: visceral
Term
What causes marasmus?
Definition
deficency of protein AND energy (calories)
Term
What 2 mechanisms are used by the body to compensate for severe caloric restriction in marasmus?
Definition
1) gradual metabolism of fat & muscle mass
2) dramatic reduction of energy utilization by reducing cellular ion pumps
Term
What is the main Sx in marasmus?
Definition
wasting
Term
Sx

marasmus
Definition
Atrophy of muscle mass & depletion of fat stores
Low metabolic activity
Growth rate decline
Mental & emotional impairment
Term
When is marasmus well compensated?
Definition
If onset is gradual
Term
What causes Kwashiorkor?
Definition
Diet adequate in calories but deficent in protein => deficit in endogenous protein synthesis
Term
Sx

Kwashiorkor
Definition
edema
heptaomegaly
mental changes
hypermetabloic state
oxidative cellular damage
anemia
depigmentation of hair & skin (scaly/brittle)
Term
What causes edema in Kawshiorkor?
Definition
decreased plasma oncotic pressure
Term
What causes hepatomegaly?
Definition
fatty liver deposits due to inability to synthesize lipid carrier proteins
Term
Why is the hypermetabolic state of kwashiorkor maladaptive?
Definition
exacerbates already low fuel stores
Term
What causes oxidative cellular damage in kwashiorkor?
Definition
imbalance in free radical producton/disposal exacerbated by:
1) inf.
2) sm. bowel bacterial overgrowth
3) selective deficency in antioxidant nutrients
Term
In which protein-energy malnutrition syndrome, which one do you see loss of appetite?
Definition
kwashiorkor
Term
def

cachexia
Definition
marasmus-like state
Term
When can patients develop cachexia?
Definition
terminal condition of chronic disease
Term
When can patients develop a kwashiorkor-like condition?
Definition
"line-fed" patients with inadequate protein intake
Term
def

obesity
Definition
excess accumulation of fat representing an imbalance b/w energy intake & expenditure
Term
def

android obesity
Definition
central/upper accumulation
Term
def

gynoid obesity
Definition
peripheral/lower accumulation
Term
What happens to fat in obesity?
Definition
hypertrophy & hyperplasia
Term
What accounts for energy expenditure?
Definition
70% - basal metabolic rate (BMR)
15% - thermic effect of food
15% - physical activity
Term
What are some medical conditions linked to obesity?
Definition
medical school (lmao jk)
HTN
T2DM
metabolic syndrome
CVD
cancer
others
Term
def

eating disorder
Definition
abberant eating practices leading to disease or disability
Term
def

AN
Definition
self-induced starvation
Term
def

BN
Definition
binging followed by excessive means to reduce caloric intake (purging, excessive exercise)
Term
def

female athletic triad
Definition
disordered eating
amenorrhea
loss of bone density
Term
def

binge eating disorder
Definition
binging with no purging
Term
def

baryophobia
Definition
underfeeding children to prevent future obesity, CVD, etc
Term
What complications are seen in AN?
Definition
protein-energy malnutrition
anemia
depression
Term
What complications are seen in BN?
Definition
demineralization of teeth
electrolyte imbalance
esophagus/stomach damage
Term
def

iatrogenic nutritional disease
Definition
physician-induced malnutrition induced by therapeutic drugs
Term
What patients in the hospital must nutrition be monitored?
Definition
1) Certain medical diseases
a) with medically relavent nutritional aspects
b) with substantial excretory loss of nutrients
c) with therapeutic intervention that induces malnutrition
2) ill/surgical patients (due to increased metabolism)
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