Unit 2-2 Metabolic (Protein and Diet) Flashcards
AA basics and categorization
basics- 20 AAs
have own tRNAs to be translated into proteins
-many post-translationally modified
based on chemical features- acidic or basic, P or NP
chemical constituents
essential- need from diet
nonessential- can be made from others
conditionally essential- limited capacity for synthesis
based on C skeletons: categorizes outcome of the veto acid
Glucogenic: AAs can be used in gluconeogenesis
-prod pyruvate or Kreb cycle intermediate
Ketogenic: AAs can generate Acetyl CoA then prod E via TCA cycle or ketone bodies
Burned off as CO₂- can’t be in gluconeogenesis
-ONLY leucine + lysine
protein breakdown process
-enzyme type
process
2 breakdown pathways
via peptidases
- need to be activated
- categorized by type of enzyme and the bond they cleave
- break down long peptide chains to AAs to be abs into circ
process
receptors/enzymes/transcription factors made after gene transcription and translation
chromatin unwinds
transcription factors and RNA polymerase make template RNA for translation
2 breakdown pathways
ubiquination
-targets protein for degradation in proteasomes
(ATP dependent)
degradation in lysosomes
-engulf EC proteins or pathogens and hydrolyze
(ATP Independent)
transamination process
Transamination
done by aminotransferases
-convert alpha-keto acid to AA, and in process convert another AA to an alpha-keto acid
reversible; Keq ~1
100s of aminotransferases each selective for few AAs
2 specific aminotransferases: AST and ALT
(PLP from Vit B6 used by aminotransferases to hold/transfer N groups)
NH2 has to be removed from AA to be used for gluconeogenesis
NH2 added to C skeleton to make AA
rxns typically in liver
also kidney, intestine, muscle
prototypical rxn:
AA donates NH2 to alpha-ketogluterate to prod L glutamate and an alpha keto acid via aminotransferase
NH3 then released w/ regeneration of alpha ketogluterate
-NH3 is toxic; needs to leave via urea synthesis
urea cycle process
overall rxn:
3ATP + HCO3- + NH4+ + aspartate –> 2ADP + AMP + 2Pi + PPi + fumarate + urea
part in cyto, part in mito
ornithine is recycled in urea cycle:
Aspartate, free NH3
transaminated urea converted to carbamoyl phosphate via carbamoyl phosphate synthase 1
-1st key regulated step in protein catabolism
N from carbamoyl phosphate enters urea cycle, ultimately combined w/ NH3 from aspartate –> urea (2N)
urinary N in form of urea then represents marker of AA catabolism and oxidation
glutamine and arginine significance w/ N
Glutamine
important 2N containing AA
accepts N from other AAs in peripheral tissue, carries to liver/kidney
donates to glutamate
then glutamate to alpha ketogluterate via glutamate dehydrogenase
-2nd key regulated step in protein catabolism
Arginine
minor pathway for N removal via prod of NO
special AAs
sulfur containing- 2
aromatic AAs- 3
sulfur containing
cysteine: disulfide bridges that change protein conf
methionine:
- S-adenosylmethionine SAM
- E source for rxns, methyl donor
- precursor for homocysteine (vascular disease, wound healing, B12/folate metabolism)
- glutathione-
- tripeptide containing cysteine
- redox buffer
- protects against free radical injury
aromatic AAs
tryptophan, phenylalanine, tyrosine
precursors for serotonin, niacin, DA, NE, tetrahydrobiopterin BH4, TH
scurvy
define
signs/symptoms
Vit C role
dec collagen strength from lack of Vit C -pale skin loss of teeth sunken eyes dec vascular endothelium--> hemorrhages --> loss of RBCs (swollen gums, bruising, anemia)
Vit C is req coenzyme for hydroxyproline and hydroxylysine for collagen strength
Vitamin C, K, B6 cofactors
Vitamin C
o Coenzyme for Hydroxyproline and Hydroxylysine in collagen strength
o Pro–>Hyp via prolyl hydroxylase and Vit C
o Lys–>Hyl via lysyl hydroxylase and Vit C
Vitamin K
o Coenzyme to target proteins to membranes via Ca chelation
o Glu–>Gla via G-glytamyl carboxylase and Vit K
Vitamin B6 (PLP) o Precursor to Pyridoxal Phosphate PLP o Used by aminotransferases to hold/transfer amino groups in transamination
proteases
break down proteins into respective AAs
initially zymogens
Pepsin: stomach
pepsinogen cleaved by HCl
cleaves proteins
Enteropeptidase: intestine
activated by several, incl trypsin
cleaves trypsin
trypsin: pancreas to SI
trypsinogen cleaved by enteropeptidase to prod trypsin
trypsin cleaves all other zymogens
urea cycle and control points
o Ornithine–> Citrulline (catalyzed by Carbamoyl phosphate synthetase I )
o Citrulline + Aspartate–> Argininosuccinate (catalyzed by Arginonosuccinate synthase)
o Argininosuccinate–> Arginine (catalyzed by Argininosuccinate lyase)
o Arginine–> Ornithine + Urea (catalyzed by Arginase)
Carbamoyl phosphate synthetase I (initial step in Urea Cycle entry)
o Important urea cycle enzyme found in mitochondria.
o Rxn: HCO3- + NH3 carbamoyl phosphate
♣ uses 2 of the 3 ATPs in urea cycle.
o N-acetylglutamate is an allosteric activator of Carbamoyl phosphate synthetase I.
♣ Arginine is an activator of N-acetylglutamate synthase
• Catalyzes acetyl CoA + glutamate to N-acetylglutamate
transport of ammonia through he blood
can’t be transported through blood
most tissues:
glutamate –> glutamine via glutamine synthase
2Ns on glutamine transported to liver for urea cycle
muscles:
use alanine to transport into alanine-glucose cycle
(Pyruvate buildup from glycolysis can be –> alanine then go to liver, then back to pyruvate, and glucose can be made and delivered back to muscle)
Glu dehydrogenase: control point for protein metabolism
-controls direction of N removal or incorporation into AAs
Arginine in nerve and muscle func
cross talk and alt rxns related to urea cycle
Arginine –> citrulline via NO synthase
-prod NO NT
Arginine –> ornithine via arginase in urea cycle
or, catalyzed –> creatine phosphate for muscle E
hyperammonemia
ammonia accumulation- depletes alpha-ketoglutarate- inhibits TCA cycle
acute: tremor (asterixis**) encephalopathy seizures, ataxia, visual loss, hallucinations, mania vomiting, loss of appetite neonates: temp instability, hypervent
chronic: dev delay nausea, failure to thrive, protein avoidance migraines anxiety, depression, disinhibition hepatomegaly, elevated LFT's
triggers: illness, fever, vomiting, fasting, surgery postpartum period**, menarche intense exercise dietary protein load meds- valproate, peg asparginase UTI
tx: limit protein intake
Maple syrup urine disease MSUD
BCKCD complex deficiency
build-up of alpha keto acids in urine (sweet smell), but even more conc in earwax
branched chain AAs-
Isoleucine, Leucine, Valine
first, branched chain AAs are deaminated by aminotransferases –> alpha keto acids
then decarboxylated by BCKCD
common in Amish broad spectrum severe neonatal: irritability and poor feeding at 48hrs lethargy, opisthotonus, apnea cerebral edema, encephalopathy (Leucine accum in brain) reversible w/ tx
(I live Vermont maple syrup from b1anches)
Dx High leucine urine ketones in neonate gene sequencing: BCKDCD, DBT, DLD Diagnostic: allo-isoleucine present
Tx
thiamine supplementation
limit dietary protein
leucine-free formula, regular serum leucine levels
close monitoring of nutritional status (esp Isoleucine and Valine)
consider liver Tx
leucine is likely teratogenic
thyroid chemistry
Tyrosine used to make T4
T4 used to make T3
TSH stimulates iodide uptake and release of T4,T3
Thyroid peroxidase: oxidizes Iodide to I2
Thyroglobulin Tg: contains Tyr residues iodinated to form T4,T3
Thyroxin binding globulin TBG: transports T4,T3
Heme metabolism
porphyrias
degradation
jaundice
Porphyrin/heme metabolism:
porphyrin production:
Gly + succinyl CoA –> delta-aminolevulinic acid (ALA) via delta-aminolevulinate synthase
2x ALA –> porphobilinogen via delta-aminolevulinate dehydratase
Porphobilinogen ———-> Protoporphyrin IV via 4 enzymes
Protoporphyrin IX –> heme via ferrochelatase
derived from Gly and TCA intermediates
cyclic, made of 4 pyrroles
primarily prod in liver
binds Fe2+
porphyria- disease in porphyrin synthesis
Lead poisoning
Lead inhibits 2 enzymes for porphyrin synthesis
delta-aminolevulinate deydratase and ferrochelatase
degradation Heme --> biliverdin (green) --> bilirubin (red/orange) --> bilirubin diglucuronide --> urobilinogen --> sterocobilin (Brown)
bilirubin transported to blood via Albumin
in liver: bilirubin conjugated w/ glucuronic acid –> bilirubin diglucuronide (AKA conjugated)
in intestine: bilirubin diglucuronide oxidized –> setercobilin
jaundice: bilirubin can’t be processed properly
hemolytic jaundice- too many RBCs lyse
neonatal jaundice: conj bilirubin not prod fast enough (low leaves of bilirubin glycuronyltransferase)
cysteine
unessential AA
synthesized from Met
can form disulfide bonds w/ other cysteine –> cystine (oxidized)
-folding and structure importance
Glutathione GSH
highly soluble tripeptide that uses -SH buffer to maintain proteins in reduced form (ex - reduced heme for functional Hgb)
-controls redox pot of GSHGSSG (cysteine actually is the worker)
-protect against ROS
Methionine
essential AA
used to prod SAM, an intermediate in production of cysteine
SAM:
prod in 1st step of Met degeneration w/ ATP
-activated sulfur: roles in epigenetic, host defense, DNA methylation, maternal diet, depression tx, etc
-AKA adoMet
-major C donor; high E storage unit
2 Met options:
Met–>SAM–>SAH –> homocysteine –> Met
needs coenzymes THF and Vit B12 to transfer back CH3 group and methionine synthase
Met –>SAM –> SAH –> homocysteine –>cystathionine –> cysteine
hyperhomocysteinemia
multiple problems incl CVD
from low folate, B6, and B12 (vascular disease)
cysteine is now essential
Tx w/ folate, B6, B12
homocystinuria
(AR) defect in cystathionine-B-synthase CBS
can’t convert homocysteine to cystathionine (and eventually cysteine)
inc homocysteine has toxic effect on tissue (skeleton, eye, vasculature) and high risk of thrombotic events
Clinical presentation: mental retardation, osteoporosis, scoliosis, vascular disease, thrombosis, Marfanoid habitus (AD) (other lecture says pectus carinatum??), lens subluxation (down and in) high homocysteine in urine*
Treated pts will get osteoporosis, vascular risk
cysteine is now essential
Dx w/ elevated Hcy, need to methionine, methylmalonic acid, and B12 level
CB sequencing
Tx w/ Vit B6 to “force” CBS activity
mainstay tx is restrict methionine diet and Betaine
pts often on coumadin/anticoagulant
avoid smoking and OCPs
cystinuria
kidney stones (renal failure) defective transporter of cysteine (and ornithine, lysine, arginine- "COLA") that leads to crystallization in urea
tx w/ acetazolamide that makes cysteine more soluble (and hydration)
vascular disease
autoimmune disease where Hcy acts as a pro-inflammatory molec
B6, B12, folate in Cys and Met metabolism
B6:
homocysteine –> cysteine via CBS
B12:
homocysteine –> Met via Methionine synthase
Folate:
makes THF via DHFR
involved w/ 1-C transfers
homocysteine –> Met via Methionine synthase
Trp metabolism products
Trp –> pyruvate or acetyl CoA
Trp hydroxylated by tryptophan hydroxylase via BH4 cofactor to prod DOPA
then DOPA –> catecholamines (DOPA, DA, NE, EPI) and melanin
Trp used to prod serotonin, melatonin, and niacin
phenylketonuria PKU
most common IEM (1/15K)
defect in phenylalanine hydroxylase
build up of alternative byproducts (phenyl lactate, phenylacetate, phenylpyruvate)- phenylalanine accumulates in blood (10-20x)- toxic to brain
Phenylacetate- smells, excreted in urine
tyrosine becomes essential (NTs and melanin rely on tyrosine)
Tetrahydrobioptin BH4 supplementation (1% are from BH4 disorder- supplement w/ Sapropterin)
untreated PKU presentation: intellectual disability hypo pigmentation Eczema Hypomyelination on brain MRI
tx
avoid aspartame sweetener- contains phenylalanine
restrict dietary protein (moving target)
supplement all non-Phe AAs
monitor for iatrogenic protein malnutrition (Alb, proAlb, Vit B12, etc)
ultimate IQ directly related to initiation of tx and Phe levels in childhood
current lifelong Tx recommendation
Maternal PKU
exposure to elevated Phe in-utero is teratogenic
infants born to uncontrolled PKU mothers-
growth restriction
microcephaly
intellectual disability
heart malformations
Tyrosinemia
defect in multi-step tyrosine degradation
3 types, depending on particular dysfunctional enzyme involved
Parkinson’s disease
degenerative disorder of CNS (loss of motor skills)
loss of neurons –> low DA –> PD
tx w/ Dopa, MAOIs, CMT inhibitors to prevent deamination
BH4 cofactor uses
first degradation
Phe: phenylalanine hydroxylase
Tyr: tyrosine hydroxylase
Trp: tryptophan hydroxylase
purines vs pyrimidines
rings
DNA vs RNA
synthesis
Purine:
2 rings- pure As Gold (Adenine and Guanine)
DNA and RNA
start w/ Ribose + sugar
-activate sugar via PRPP synthase, then build base, then get to I, then to AMP or GMP, then phosphorylate to get ATP/GTP
pyrimidines 1 ring- CUT the Py RNA: cytosine and uracil DNA: cytosine and Thymine start w/ base -build until it's done (I, orotic acid), then to UMP, then UTP, then CTP add sugar at end key enzyme: carbamoyl phosphate synthase CP synthase in cyto
ribose naming
ribonucleo:
base: AGCUT (I, orotic)
side: base + sugar
tide: phosphate
de novo synthesis of purines
goes through HMP shunt
purines are build on a ribose sugar Ribose 5 phosphate comes from HMP shunt goes to 5-phosphoribosyl-1 pyrophosphate via PRPP synthase (activator Pi inhibitors Purine, ribonucleotides)
1st step is allosterically regulated, important:
PRPP synthase and Glutamine PRPP aminotransferase*
(activator Pi, PRPP
inhibitors: purines, ribonucleotides, AMP, GMP, IMP)
start w/ PRPP, end w/ IMP
convert IMP to AMP or GMP
-GTP and ATP products inhibit their own synthesis
mono to di- and tri- forms:
base specific nucleoside monophosphate kinases:
bidirectional enzymes
adenylate kinase for ATP’s
guanylate kinase for GTP’s
nucleoside diphosphate kinase for GDP/ATP mix and CDP/ATP mix
de novo synthesis of pyrimidines
starts w/ CO₂ and glutamine
ends at UMP
key regulated step: carbamoyl phosphate synthase II
UTP to CTP via CTP synthase
conversion of ribonucleotides to deoxyribonucleotides
enzyme: deoxyriboATP is an inhibitory regulator
ribonucleotide reductase: ribonulceoside DP to deoxyribonucleoside DP
-activity site regulated by ATP and dATP on/off switch
substrate specificity site: determines which dNTP is made
remember deoxyATP shuts thing down*, ATP turns it on
dUMP to dTMP
THF is methyl donor
methotrexate is inhibitory
CPS I vs CPS II
CPS I: mito urea cycle ammonia is N source activator: N-acetyl glutamine
CPS II: cytosol pyrimidine synthesis gamma-amide group of glutamine inhibitor: UTP activator: ATP
purine degradation
starts w/ AMP or GMP
ends w/ uric acid
key enzyme 1: ADA
key enzyme 3: xanthine oxidase
body takes AMP –> I
–> GMP –> hypoxanthine –> xanthine –> uric acid
key enzyme: xanthine oxidase (inhibited by allopurinol)
salvage pathway to reuse bases so you don’t have to keep re-making them
AMP degeneration goes through adenosine to get to inosine (free base)
key enzyme: adenosine deaminase
lots of A and G breakdown means lots of uric acid
-can ppt out into kidney stones or gout
pyrimidine breakdown
C and U have similar pathways
lead to malonyl CoA and acetyl CoA
ends up as succinyl CoA
salvage pathway for purine synthesis
wait until you have some PRPP to rebuild them back up
enzymes:
hypoxanthine-guanine phosphoribosyltransferase for hypoxanthine and guanine turning into IMP and GMP
adenine uses adenine phosphoribosyltranfersase to AMP
Lesch Nyhan Syndome
deficiency of hypoxanthine-guanine phosphoribosyltransferase
-inability to salvage hypoxanthine or guanine
inc levels of PRPP and dec IMP and GMP
causes inc de novo purine synthesis
causes excess uric acid prod, neuro features
-self-mutilation, involuntary movements (lip/finger biting, head banging)
severe combined immunodeficiency syndrome SCID
bubble boy
pts lack active adenosine deaminase ADA
deoxyadenosine builds up
excess dAMP converted to excess dATP, which inhibits ribonucleotide reductase, preventing synthesis of other dNTPs –> lymphocyte toxicity
rapidly proliferating cells are affected, incl lymphocytes
tx w/ gene therapy
gout
elevated uric acid levels in blood and urine
overproduction of purine nucleotides via the de novo pathway
excess purine degradation –> uric acid
deposition of uric acid crystals –> inflamm response and pain
long term cartilage destruction
drugs that target nucleotide metabolism
drugs that slow nucleotide synthesis are effective against viruses, bac, and cancer cells that are rapidly dividing
newborn screening
principles
NBS tandem mass spec to test for ~50 disorders simultaneously
principles:
inborn errors: recessive inheritance
start w/ metabolite that’s high or low
(many respond to tx w/ cofactors)
Dx by testing gene, enzyme, and metabolites
just because we can test for something, doesn’t mean we should (Varies by state)
pre-test probability
Bayesian reasoning: even w/ good test, post-test probability is still low if pre-test probability is still very very low
-postive predictive value 5%
tyrosinemia Type 1
AKA hepatorenal tyrosinemia
fumarylacetoacetate hydrolase deficiency
serum AAs will show mild-mod tyrosine elevation
Dx w/ succinylacetone in urine
typically presents as acute liver failure in infancy
later, hepatocellular carcinoma
hyperbilirubinemia, jaundice, ascites, coagulopathy, hepatomegaly, rickets (wide wrist*)
acute neurologic crisis w/ abd pain and neuropathy due to secondary porphyria
tx:
unusual paradigm
NTBC meds to induce different/milder metabolic disease (tyrosinemia 3)
-NTBC needs dietary therapy to prevent oculocutaneous manifestations
still need monitoring for hepatocellular carcinoma HCC
-liver Tx may be necessary if HCC is present at Dx
Tyrosinemia type 2
AKA oculocutaneous tyrosinemia
4-OH phenylpyruvic acid dehydrogenase deficiency
causes really high tyrosine elevations
no acute decompensation
palmoplantar hyperkeratosis and keratitis
tx:
managed according to other AA disorders-
limit Phe and Pyr in diet
supplement other AAs
ornithine transcacrboxylase OTC deficiency
X-linked, deletions/point mutations in OTC
gene expressed only in liver
many symptomatic females
most common urea cycle disorder
often lethal in neonatal boys
symptoms of hyperammonemia
dx
diagnostic metabolite is orotic acid (part of pyrimidine synthesis pathway)
also w/ low citrulline, high glutamine, low BUN
no megaloblastic anemia (vs orotic aciduria)
tx not on newborn screening ammonia scavenger meds -Sodium phenylacetate -Sodium benzoate Excreting otherwise unusable AAs too, though, so supplement diet VERY LOW protein diet supplement citrulline or Arg aggressive support during illness dialysis liver tx gene therapy?
lysosomal storage disorders- general
focus on phenotype and specific tx’s
common theme-
gradual, progressive accum of toxic lysosomal substrates, usually in lysosomes
most are AR
(EXCEPT Fabry XLD, Hunter XLR- “men hunt”, and Danon XLD)
causes buildup of earlier pathway- can’t get rid of end product
gradual accum of moderately toxic sub’s
chaperones can bind to help deficiency func a little better
rare diseases (~50 recognized LSD’s)
what does storage look like
skin: coarseness, angiokeratoma
skull/brain: macrocephaly, cognitive regression
eyes: corneal clouding, cherry red spot
E/N/T: macroglossia, sleep apnea, full face
Heart: cardiomyopathy
Liver: HSM
Kidneys: proteinuria
Skeletal: dystosis multiplex (vertebral breaking, broad metacarpals and phalanges base), joint stiffness, short stature
Gaucher Type I
AR inheritance
Beta glucosidase (glucocerebroside) (tx w/ this)
adult onset
HSM
anemia/low plts (pancytopenia)
skeletal- Erlenmeyer flask deformity (Xray)
classic “Gaucher” cell in bone marrow- crumpled tissue paper
Tay Sachs Type I
AR inheritance
beta-hexosamidase A
cherry red spot (CLASSIC) inc startle reflex no HSM (vs Niemann-Pick) progressive neurodegeneration onion skin lysosomes
Sandhoff disease
AR inhertiance
looks like Tay Sachs but has HSM AND bony disease
both beta-hexosaminidase A (Tay Sachs) and B
HSM
Fabry disease
XL inheritance (F have delayed disease)
alpha galactosidase
(give for Tx)
angiokeratomas (bathing trunk distribution)
renal failure- proteinuria**
acroparethesias (palm and sole pain)
nl IQ
Niemann-Pick disease
AR inheritance
sphingomyelinase supra nuclear gaze palsy cherry red spot** on macula BIG HSM lipid-laden macrophages- "foam cells"
Pompe disease
AR inheritance
alpha-glucosidase
(give for tx)
men: infant w/ profound weakness (hypotonic- floppy baby) and hypertrophic cardiomegaly**
OR
adult w/ proximal muscle weakness and sleep apnea
“Pompe trashes the pump”- heart, liver, and muscle
Hunter disease
XL inheritance (females have no disease)- “men hunt”
iduronate sulfatase
(give for tx)
coarse-appearing child, who is short, HOARSE voice, freq URIs, some learning problems
NO corneal clouding (vs Hurler)
Hurler disease
AR inheritance
alpha iduronidase
(give for tx)
similar to Hunter (can occur in girls)
coarse facies, big HSM, major skeletal problems
CORNEAL CLOUDING
McArdle disease
AR inheritance
Glycogen phosphorylase
muscle cramping after exercise
myoglobuinuria (coffee colored urine after exercise)
losses and fuel requriements
don’t change if you stop feeding (and may even inc)
CO₂
insensible: skin, stool, growth, dev
a sick pt will switch to malnutrition/shrinking faster than nl/healthy pt
-poor nutritional stores
nutritional depletion- when to feed
this is when you should be moving towards feeding
nl, not sick- 10-14 days
nl, pretty sick; OR nutritionally depleted (not sick)- 5-7 days
nutritionally depleted AND sick 3-5 days
need to assess pre-morbid nutritional state
-Hx of alcoholism, homelessness, unusual diet, elderly, disabled
chronic med probs (GI, pulm, renal, cancer)
prior weight loss before hospital
Thenar or temporal wasting
low Alb (t1/2= 20 days) (pre-albumin)
lymphocyte count <1500
how much to feed hospital pt
E intake should equal expenditure
Harris Benedict eqn
Indirect calorimetry
Swan Ganz O₂ balance using Fick Principle
Sick-o-meter: 25-35 kcal/kg/day
-sicker/bigger the person the, greater the E requirement
what route to feed hospitalized pt
enteral:
feed through GI and body
may improve gut barrier func
even small amount of nutrient to gut may help
parenteral
central IV cath
assoc w/ risks at time of placement and during therapy
-if you can avoid this, feed enterally
-aspiration pneumonia, problems placing tube, infection
initiating tube feeding
-place NG tube, make sure it’s in place
start tube feeding slowly, 10-20mL/hr
check for residuals 5-10 hrs
gradually inc flow rate and continue to check residuals (vol left in stomach)
->100 residual means to dec feedings
if residuals persist, reposition pt, elevate bed, R lateral decubitus position
bolus or continuous infusion options
keep track- often times pt becomes NPO for procedure/dx test
continue to inc rate until target/goal infusion rate is reached
what to feed hospital pt
ask for enteral feeding formulary
ex. DH standard tube feed is "Jevity" 1 kcal/mL protein- cheap, long shelf life, not all essential AAs carb fat- cheap, long shelf life vitamins, micronutrients
1.321 L/day to get “RDA” for 70kg person
ex write diet 90kg x 35 kcal/kg/day = 3150 kcal/day 3150mL/24 hrs = 131 mL/hr already getting 1.2L/day D5 5% glucose = 5g/100mL or 60g/day glucose, or 60x 4kcal/g = 240kcal/day reduce enteral calories by 240
ex 2
60kg x 30kcal/kg/day = 1800kcal/day or 1800mL/24 hrs or 75 mL/hr
how to determine adequacy of feedings
check/record total cal/day (often what’s written isn’t actually what’s delivered)
overfeeding causes hyperglycemia
-occurs 1-2 days after inc admin because glycogen pool buffers
may take 1-2 days to resolve
N balance, 1 week after you get target infusion
AA catabolism going to NH3 and urea cycle
need to eat insensible losses
if BUN is stable then most of UUN represents the oxidation of protein
usual protein requirement is 0.5-0.8g/day in illness (or more in ill, burn, post-op)
protein balance= protein in - protein out
g protein out = (2g skin + 2g stool + 24hr UUN) x 6.25
vitamins in hospital pts
fat soluble: ADEK
larger pool size, depleted slowly
water soluble:
♣ C deficiency is scurvy: petechii, hemorrhage
♣ B9 folate deficiency: anemia natural problems
♣ B3 Niacin deficiency: Pelagra: dementia, dermatitis, delirium
♣ B1 Thiamin deficiency: Wernecke Korsakoff, Beri Beri: CHF abnl neuro func
Much smaller pool size; can be depleted quickly
micronutrients in hospital pts
o Zn deficiency: diarrhea
o Fe deficiency: anemia, immune dysfunc, but supplementation when transferrin is low has risks
o Cr deficiency: insulin resistance
o Selenium deficiency: CHF (Keshan’s disease)
Special nutrients in hospital pts
Arg
Glutamine
Special lipids
Arg not very stable in enteral formulations "conditionally essential" precursor for NO direct immunomodulatory effects- measured by response to mitogens supplementation improves N balance stimulates GH and insulin secretion
Glutamine
preferred nutrient for gut epi
conditionally essential- requirements inc w/ illness and neg N balance
supplementation inc immune func, gut histo, barrier func, and N balance
special lipids
very little omega-3 FAs in standard house formulas
long chain polyunsat FAs are precursors for leukotrienes and prostaglandins
supplementation may improve tissue perfusion, dec prod of cytokines, and free radicals
MCT (C6-C12) may be alt to carb without hypertriglyceridemic effects of more traditional fat sources
special hospital pt conditions
resp failure
diaphragmatic weakness
inc work of breathing at weaning from ventilator
high carb diet and overfeeding inc resp quotient
inc CO₂ production inc min ventilation, work of breathing, and vent pressure
higher fat and less calories may be beneficial *
special hospital pt conditions
liver failure
pre-existing nutritional deficiency is common
insulin resistance is common
hepatic encephalopathy in part from inc blood ammonia level
in part due to “false NTs”
diets lower in aromatic AAs and higher in branched AAs may be helpful**
special hospital pt conditions
renal failure
acute vs chronic likely important distinctions
vol (Na and water) overload is problem**
protein oxidation leads to inc BUN, but need adequate protein
N balance- calculation eqn
special hospital pt conditions
burns, trauma, post op
pts are healing
may have inc insensible losses (bleed, drains, pus, etc)
inc E requirement may be as high as 30-35kcal/kg/day
may have inc protein req 1-1.5g/kg/day
special hospital pt conditions
re-feeding
malnourished pts who have lost weight, or prolonged period of poor nutrition are at risk
complications:
hypophosphatemia, hypokalemia, diarrhea, Wernicke’s encephalopathy (acute thiamine B1 deficiency)
begin w/ thiamine, folate, and multivitamin soln IV
begin feeding slowly, monitor electrolytes
special hospital pt conditions
diabetic diets
primary goal is similar amounts (known amounts) of carbs at each meal
classic 1800 cal “ADA” diet
-may be under or overfeeding pt with this
hospital may be good time for pt to learn about diabetic nutrition and diabetes
public health issues at risk for nutritional problems
chronic disease, heart disease, cancer, obesity, HTN, stroke, diabetes, international nutrition issues
diet and physical inactivity is single largest cause of death
ambulatory medicine
pregnancy, lactation, breastfeeding
healthy, growing children
obesity, HTN, hyperlipidemia, T2DM, elderly, chronic disease, CF, COPD, celiac, micronutrient deficiencies
nutritional support/in-pt
ICU, surgical, short-gut syndrome/feeding intolerance, premature infants
enteral or parental feeding
pts at high risk for nutritional depletion or excess
old/young
underweight or rent loss of >10% body weight
obese w/ central adiposity/insulin resistance
limited variety in consumption
protracted nutrient losses: malabs, enteric fistula, draining abscesses/wounds, renal dialysis, chronic bleeding or RBC destruction, s/p bariatric surgery
hyper-metabolic states- sepsis, protracted fever, extensive trauma, burns
chronic use of alcohol, meds w/ anti-nutrient or catabolic properties
marginalized circumstances (poverty, age, isolation, altered MS including ID)
anthropometrics
lenght/height
weight
waist circumference
etc
reflect growth and dev
pediatrics: use growth charts
adults: BMI
clinical signs on exam of malnutrition
skin- rash, petechiae, brushing, pallor hair- pluck ability, color change, texture mouth- sores, cracks, tongue eyes loss/gain of subcutaneous fat muscle wasting edema- extremities, sacral neuro- reflexes, vibratory sense, balance, gait, Romberg, mental status
labs indicating malnutrition
specific but not sensitive
Albumin- reflects protein synthesis, but levels dec w/ stress/inflamm
prealbumin- short half life- reflects more acute status but also dec w/ stress
transferrin- iron and protein status
CBC and total lymph count
specific nutrient levels (vitamins, micronutrients, etc)
nutrient requirements from RDAs
nutrient standards- EAR, RDA
My Plate- 2015 DGA w/ 5 major themes
healthy eating pattern
focus on variety, nutrient density, amounts
limited calories from added sugars and sat fats, and dec Na intake
healthier choices overall
be active
-applies more to dinner; doesn’t address portions; doesn’t represent total day/diet
nutrient standards
current shift in emphasis from preventing deficiency to decreasing risk of chronic disease through nutrition
estimated avg req EAR:
-assess inadequate intakes and planning goal intake for mean intake of a GROUP
recommended daily allowance RDA
avg daily intake sufficient to meet nutrient requirement of nearly all INDIVIDUALS in life stage and gender group
should be used as goal for dietary intake by healthy individuals, not to assess/plan diets of groups
nutrition assessment overview
should be part of ROUTNE medical eval
dietary assessment:
qualitative (variety, excess, gaps)
quantitate (est of typical day, food diary)
sources of data for estimating nutrient requirements:
nutrient intake data/epidemiological observations
biochem measurements relative to intake
experimental depletion-repletion studies
how to being to address dietary/lifestyle changes in pt
failure to change diet in most pts is excessive difficulty/barriers, NOT motivation
to achieve change: reduce difficultly or inc motivation
“readiness to change” 2 key concepts:
-importance and confidence
starting point is to ask pt to describe diet and activity level
-ask if they see potential for change, and how they’d like to be (collaborative goal setting)
key messages of 2015-2020 DG
follow healthy eating pattern across lifespan
-eating pattern combo of foods/drinks over time
Healthy US style:
variety of fruits/vegetables, grains (whole), low-no fat dairy, protein variety, plant oils and those naturally present in foods
Healthy Mediterranean:
more fruits, seafood
less dairy
breads and cereals (unrefined)
fruits and veggies
nuts, olive oil, fish
limited: sat fats, meats, full fat dairy
Healthy Vegetarian:
more legumes, soy, nuts, seeds, whole grains
no meats, poultry, seafood
focus on variety, nutrient dense, and amount
limit sugars, sat fats, and Na intake
shift to healthier choices
support healthy patterns for all
current US diet vs DG
Americans consume:
too few green/orange vegetables, legumes, whole grains, fruits, low fat dairy, seafood
too much Na
too much solid fats, sugars, refined grains, Na
caloric intake exceeds E expended
general water vs fat soluble vitamins
water soluble: generally not stored (Except B12), but chronic intake affects tissue levels highly abs from diet excreted via urine low toxicity
fat soluble:
accumulated “stores” in body
req abs of dietary fat and a carrier system for transport in blood
potential for toxicity w/ excessive intake
vitamin A
AKA Retinol
photochemical basis of vision
conjunctival membrane and corneal maintenance
Epi cellular differentiation and proliferation
sources:
preformed: liver, dairy, egg yolks, fish oil
precursor (carotenoids- beta carotene): deep yellow/orange and green veggies
biochemical eval: serum retinol (nl levels until liver stores nearly exhausted)
deficiency:
night blindness, xerophthalmia (dryness), Bitot’s spots on sclera, eventual blindness
immune deficiency
abnl epi morphology- flattened, dry, keratinized
Vit A tx in measles assoc w/ dec morbidity/mortality
at risk:
low intake
fat malabs (liver disease, low bile salts, pancreatic insufficiency)
protein E malnutrition
toxicity
ONLY W/ PREFORMED VIT A RETINOL, dose dependent
vomiting, inc ICP, HA
bone pain (periosteal proliferation), bone mineral loss (fractures and osteoporosis)
liver damage
death, birth defects
Vitamin D
hormone
maintains Ca conc’s
stimulates Ca, P abs and mobilization from bone
innate immune func (free radicals)
cell growth and differentiation through receptors
sources
precursor (dehydrocholesterol): skin, converted to cholecalciferol Vit D3 by UV light
dietary: natural (fish oils, egg yolks)
dietary fortified: milk, D3 formulas from animals, D2 ergocalciferol from plant/algea
-D3 activity 2-3x > D2
metabolism
abs via chylomicrons
Vit D2/3 hydroxylated in liver to 25-hydroxycholecalciferol; then in kidney to 1,25-dihydroxycholecalciferol (calcitrol) = active from
recommended intakes supplement all breastfed infants until 500mL/day of formula/milk non-breastfed infants: fortified milk other: 5-15 min sun exposure 600 IU/day children and adults total upper limit 4000 IU/day
biochemical eval serum 25(OH) Vit D levels- reflect nutritional status
deficiency
<29 ng/mL
rickets-
failure of cartilage maturation and calcification
“rachitic rosary” on ribs, bowed legs, widened metaphases (esp wrist), bone pain, fractures,
dec serum Ca and P
inc Alk Phos (+ classic triad = late findings)
dec 25(OH) Vit D and inc PTH
autoimmune disease, NM func, heart disease, Cancer, overall mortality
at risk: new epidemic w/ indoor time? AA females of childbearing age breastfed infant, esp if deficient mother low dietary intake, fat malabs Orlistat- intestinal lipase inhibitor dark skin obesity (sequestered in fat) liver/renal disease- need calcitriol to activate elderly
toxicity
hypervitaminosis
risk w/ chronic granulomatous diseases (sarcoidosis)
>10K IU/day x weeks
hypercalcemia, vomiting, series, nephrocalcinosis, soft tissue calcification
Vitamin E
antioxidant
free radical scavenger
cell membrane stabilizer
sources:
polyunsat vegetable oils
wheat germ
deficiency
neuro dgeneration, w/ loss of DTRs, spinocerebellar ataxia, neuropathy, ophthalmoplegia, incoordination, loss of vibration/position sense
hemolytic anemia
at risk:
prematurity
fat malabs syndromes- short gut, CF
toxicity
low, coagulopathy (very large doses inhabit Vit K dependent factors)
megadoses for protection against heart disease and/or cancer NOT supported by most lit
Vitamin K
carboxylation of coag proteins 2,7,9,10
sources:
leafy veggies, fruits, seeds
synthesized by intestinal bac
recommendation
all newborns should receive single IM injection 0.5-1.0mg
deficiency
prolonged coag times
hemorrhagic disease of newborn*
-bleeding into skin (purport), GI tract, CNS
at risk new borns (poor placental transport, sterile gut, low clotting factors) late, esp breastfed infants fat malabs syndromes chronic Antibiotic use
summary of fat and water-soluble vitamin deficiency findings
Vit A: rash/skin findings, eye findings/blindness, immune
Vit D: rickets, osteopenia/malacia, growth failure
Vit E: neuro, anemia
Vit K: rash/skin, (anemia)
Thiamin: neuro, CHF (wet BeriBeri)
Riboflavin: mouth lesions, conjunctiva
Niacin: rash/skin, (neuro), diarrhea, 3D’s
Folate: mouth lessons, anemia
B12: mouth lesions, neuro, anemia
B6: mouth lesions, neuro, anemia
Vit C: rash/skin, mouth lesions, (neuro), anemia, joint pain
Energy releasing Vitamins
Hematopoietic vitamins
other B vitamin
other water soluble vitamin
E releasing
Thiamine B1
Riboflavin B2
Niacin B3
Hematopoietic
Folate B9
Cobalamin B12
other:
Pyridoxine B6
other water soluble:
Ascorbic Acid Vit C
Thiamine
B1
TDP: coenzyme for metabolism in all cells, esp glycolysis, TCA, AA metabolism, decarboxylation, transketolation rxns
TTP: thought to bind at Na channel in nerve membranes
sources
whole grains (high in germ)
enriched grains, lean pork, legumes
recommendations
1.1-1.2 mg/day
tx for deficiency- 50-100 mgIM or IV
biochemical eval
erythrocyte transketolase activity
blood thiamine levels
deficiency Beriberi Wet- Cardiac edema high output cardiac failure sings/symptoms of dry BeriBeri
dry- paralytic/nervous peripheral neuropathy w/ impairment of sensory, motor, reflex funcs affects distal > proximal limbs muscle tenderness, weakness, atrophy foot/wrist drop
Wernicke-Korsakoff Syndrome (cerebral Beriberi)
confusion/amnesia (only partially reversible)
ataxia
“triad” of ocular signs- nystagmus, ophthalmoplegia
-genetic predisposition unmasked by EtOH abuse, dietary deficiency
at risk: alcoholics elderly high car diet refeeding bariatric surgery Asian- diet of refined rice
Riboflavin
B2
FAD and FMN coenzyme functs redox rxns in TCA oxidative phosphorylation AA and FA metabolism Vit K, folate, B6, and niacin metabolism
sources liver, wheat germ dairy= largest US intake meats, poultry leafy greens
recommendations
1.1-1.3 mg/day
biochemical eval
RBC glutathione reeducate activity coefficient EGRAC (inc in deficiency)
deficiency
oral-ocular-genital syndrome
Cheilosis and angular stomatitis
inc vascularization of conjunctiva, photophobia
seborrheic dermatitis and scrotal dermatitis
at risk: isolated deficiencies rare in US women, infants, elderly, adolescents <1 C milk/week subclinical deficiency: women on OCP, elderly, eating disorder, chronic disease
Niacin
B3
nicotinamide is substituent of NAD and NADP
E-related pathways: glycolysis, TCA, oxidative phosphorylation, FA synthesis/oxidation
sources
Preformed: meat, poultry, fish, PB, legumes
Precursor: Tryptophan- milk/eggs
recommendations
14-16mg/day (1mg Niacin = 60 mg tryptophan)
Tx deficiency w/ 50-100mg 3x/day for 3-4 days
biochemical eval
urinary excretion of N1-methylnicotinamide and 2-pyridone (ratio <1 deficiency)
serum niacin
deficiency
Pellagra: 3 (4) D’s
dermatitis (symmetric pattern, aggravated by sun/heat)
dementia (confusion, dizziness, hallucinations)
diarrhea
(death)
at risk
appears after months of poor intake
corn as major protein source
general malabs, alcoholism, cirrhosis, metabolic shunting
Hartnup disease (defective tryptophan abs)
isoniazid drug treatment (for TB)
toxicity
nontoxic 3-6g/day
used to lower serum cholesterol, esp LDL
initially causes peripheral vasodilation and flushing
less common: inc serum uric acid, glucose intolerance, liver damage
Folate
B9 1-C transfers, esp syn of nucleic acids and AA metabolisms homocysteine --> Methionine conversion methyl donor epigenetic
sources:
“foliage” deep green leaves, broccoli
orange juice, whole grains (destroyed w/ cooking)
recommendations
400microg/day
women 400microg/day to prevent neural tube defects
600microg/day during pregnancy
biochem eval
RBC folate- reflects tissue stores/chronic status
serum folate- recent intake
deficiency at risk: pregnant women infants/children w/ un-supplemented goats milk meds: Dilantin, sulfasalazine chronic hemolytic anemia or blood loss
Cobalamin
B12
closely related to folate metabolism and 1-C transfers
metabolism of odd-length FAs
helps form methionine
isomerization of methylmalonyl CoA to succinyl CoA
protein and nucleic acid synthesis
abs and homeostasis
cleavage and binding to IF secreted by parietal cells
C-IF complex abs in distal ileum into portal circ
liver stores 1-10mg
-can take yrs to dev deficiency
sources
animal products only!
recommendations
2.4microg/day
slow turnover
US intakes generally»_space;> RDA
biochemical eval serum B12 level urine or blood methylmalonic acid (inc in deficiency) serum homocysteine (inc in deficiency) CBC (inc MCV- nonspecific)
deficiency at risk inadequate abs -pernicious anemia (IF problem) gastric atrophy stomach/ileum resection strict vegan/vegetarian breastfed infant of deficient mother autoimmune- Ab's to IF
Pyridoxine
B6
critical in AA metabolism, interconversions, NTs
sources
animal products, vegetable,s whole grains (lost in processing)
recommendations
1.5mg/day
biochemical eval
pyridoxal phosphate
homocysteine
deficiency
anemia, seizures, glossitis, +/- depression
at risk isoniazid meds renal disease malabs elderly
toxicity
doses >500mg/day: sensory ataxia, impaired position/vibratory sensation
-partially reversed w/ d/c of supplement
Ascorbic Acid
Vit C
antioxidant/reducing agent (e- donor)
collagen synthesis
Fe3+ –> Fe2+ reduction
NE synthesis
abs and homeostasis through acitve/saturable process- dose dependent low doses abs 100% usual intake 30-180mg/day abs 70-90% dose >1.5g/day abs ~50% if taking large total intake- best to divide the doses throughout the day renal exrection inc w/ intakes >80mg max pool size ~2000mg
sources
fruits, vegetables, esp broccoli, green pepper, potatoes
recommendations
75-90mg/day (+35mg for smokers)
safe upper limit 2g/day
biochemical eval
leukocyte or plasma ascorbic acid level
deficiency
scurvy
defective collagen formation in capillary basement membranes, loss of precursor catecholamines and other vasoactive and neurotrophic sub’s
petechiae, bleeding gums, anemia, brushing, weakness/fatigue, joint pain
at risk
low fruit/veg intake
inc requirement for wound healing and burns
income
smokers
infants fed cow/s milk w/o supplementation
trace element overview
trace if you need <100microg?/day
Fe, Zn, Cu, Se, F, Mn, etc
bioavailability: trace minerals are esp susceptible to interferences w/ abs
nutritional defects early stages of dev are detrimental to brain dev
Fe
~5g total n body
50% as Hgb Fe, 10% myoglobin, 5% enzymes
storage adults 300-1500mg
tissue oxygenation O₂ transport in blood and muscle via Hgb and myoglobin ETC oxidases/oxygenases to activate O₂ CNS myelination: DA synthesis
sources
heme: meat/flesh, liver
non-heme: plant (legume, whole grains, nuts)
-Fe fortified foods (infant formula, cereals/grains)
homeostasis
form: Heme Fe»_space;> non-heme
Ca: only dietary factor that can dec heme Fe abs
pos facts: ascorbic acid, meat or fish
neg: phytate (bran, oat, beans, rye), Ca, polyphenols (tea, some veg’s), dietary fiber, soy protein
prox duodenum Fe3+-->2+ for better abs once abs, very well retained/recycled loss/excretion: bleed, cell slough host status: deficiency --> inc abs inflamm--> dec abs
Hepcidin
blocks transport of Fe
high (inflamm)- lots of Fe uptake; high ferritin inside cells
lab values
stores:
ferritin- liver, bone marrow, spleen
inflammation–> inc hepcidin–> dec uptake
always obtain inflamm markers w/ ferritin level
transferrin: transports Fe in body; ~no “free” Fe
deficiency
poor bioavailability dietary Fe- plant/cereal staples
inadequacy- eg excessive milk intake
high demand- hemolysis, pregnancy/infancy, low stores at birth, chronic immune-stimulation (inc Hepcidin)
at risk breast fed infants >6 mo premature infants young children-poor intake young girls pregnant women blood loss obese (inflamm) s/p bariatric surgery
most common micronutrient deficiency in world
-older infants and toddlers
deficiency effects
Fe is prioritized to the RBCs- vital role in O₂ transport
lost hepatic stores, then skeletal muscle/GI, then Cardiac, then brain, then Finally RBC Fe
fatigue, listlessness, irritability, attn deficit, sleep disturbances (RLS)
impaired growth
anemia (microcytic, hypochromic)- dec O₂ carrying capacity
impaired cognitive func in developing brain (irreversible!)
recommended intakes 0.27mg/day 0-6mo 7-11mg/day 1-13 yo 14-18 yo: M 11; F 15 19-50 yo: M 8; F 18 >51 yo: 8
toxicity
potent pro-oxidant- avoid unnecessary supplementation
hereditary hemochromatosis: defect in Hepcidin- excess abs –> Fe accum–> over damage
Fe overdose = toxic
-hemorrhagic gastroenteritis, shock, liver failure, +/- fatal
clinical implications
Fe deficiency (w/o anemia) is very common
-behavioral and learning/dev effects
critical window of brain dev
in setting of acute inflamm/illness:
-abs will be poor due to Hepcidin stimulation (esp in chronic immune-stim in developing countries)
-administering Fe is ineffective- pro-inflammatory
phytic acid
binds cations- Zn, Fe, Ca- in gut lumen
humans don’t have phytases- cannot digest these
most common feed enzyme added to animal diets
high in grains, legumes: maize>wheat > legumes > rice
globally, likely major cause of dietary insufficiency disease
Zinc
total ~2g
regulation of gene expression (Zn fingers)
stabilize molec structures
co-factor for 100s enzymes
modulates activity of hormones and NTs
growth and cell/tissue proliferation (immune sys, wound healing, GI tract integrity, skin, somatic/linear growth), antioxidant, sexual maturation
sources widely dist but animal sources are richest, esp beef plants: whole grains, legumes breast milk: adequate for first 6mo
Zn homeostasis abs
2 determining factors: amount of Zn ingested, and Dietary phytate
role of GI:
abs ~ crude control
endogenous Zn- secretion, reabs/excretion
can excrete Zn, no stores
Deficiency
mild
growth delays, anorexia, impaired immune func, common
moderate-severe
dermatitis (periacral-periorifcal), personality changes, immune dysfunc, delayed sexual maturation, anorexia, diarrhea,
inherited defect in Zn abs: acrodermatitis enteropathica AE or transient neonatal Zn deficiency
stunting and hypogonadism
who's at risk Breastfed infants >6mo and young children- high growth, low intake pregnant/lactaing women elderly monotonous, plant-based diet GI illness/injury wounds/burns Celiac, CF, liver disease elderly and pneumonia
stunting strongly assoc w/ Zn deficiency
Zn supplementation in stunted populations:
+ effect w/ diarrhea, pneumonia, and childhood death prevention
Zn toxicity
LOW- much less so vs Fe
-high doses dec Cu abs and dec HDL-cholesterol
high dose Zn lozenges for few days for acute pharyngitis
assessment of Zn status- challenging
no sensitive biomarker
signs/symptoms of Zn deficiency can be nonspecific
good Hx, ROS, GI path, etc
protein Energy malnutrition
global magnitude of PEM
multi-nutritional deficiency complex
E deficiency most outstanding
E requirements “trump” all
if neg E balance, obligatory negative N balance
global 20% children underweight 26% stunted (chronic malnutrition) 8% wasted (acute) ~45% child deaths due to malnutrition
marasmus
severe Muscle wasting
E deficiency
slower onset, better adaptation
lots of:
weight loss
muscle loss
fat loss
some psych changes, infections, diarrhea,
sometimes anorexia, hair changes
NO edea, hepatomegaly, skin lesions
Kwashiorkor
generally w/o wasting
edematous PEM
protein deficiency (+ metabolic stress + micronutrient deficiency)
rapid onset, mal-adaptation
Lots of: edema psych changes anorexia infections
some:
hepatomegaly,
weight loss
diarrhea, skin lesions, hair changes
minimal:
muscle loss, fat loss
Hyperalbuminemia and edema are key
inc insulin, dec lipolysis (esp w/ continued CHP)
inc hepatic FA syn –> fatty, enlarged liver
signs:
misery, edema, Hepatomegaly
erythematous, hyper pigmentation, “flaky paint” rah
dry, brittle, “flag sign” hair
starvation
pure caloric deficiency
host adapts to conserve lean body mass and inc fat metabolism
cachexia
associated w/ inflammatory or neoplastic conditions
not reversed by feeding: anorexia
sarcopenia
subnormal amount of skeletal muscle, w/o weight loss
causes of protein energy malnutrition
at risk for PEM
social and economic: poverty ignorance inadequate breastfeeding inappropriate weaning monotonous/restricted diets, plant-based
biologic factors
maternal under-nutrition
low birth weight infants- persistence of effects
environmental factors
-overcrowding, infectious burden, agricultural patterns, etc
at risk
infants 0-12 mo marasmus
12-24 mo esp Kwashiokor, voluntary restrictive/aternative feeding
acute weight loss: anorexia nervosa, s/p bariatric surgery, intentional restriction, social deprivation
chronic illness: alcoholism, pancreatitis, HIV/AIDS, malabs
elderly: wasting/loss of LBM (sarcopenia)
PEM definitions/classifications
underweight, stunting, wasting
underweight low eight for age >2 SD's below median (50th %ile) <3rd %ile for age underweight doesn't mean wasting- height also plays factor
stunting- “chronic malnutrition”
length for age
stunting < -2 Z score length/age
severe stunting: < -3 Z score
wasting
dec weight relative to length (~BMI)
ideal body weight 50th %ile weight/height
mild wasting: 83% IBW (failure to thrive, undernutrition)
moderate wasting: 75-79% IBW
severe wasting: <75% IBM
adults: wasting BMI <18, severe <16
metabolic response to starvation
fuel utilization
marasmus
nl response to starvation
Fuel utilization during starvation ♣ First glucose will gradually come down ♣ Start to form ketone bodies ♣ Switch to relying on FAs ♣ Blood sugar remains in nl range- gluconeogenic AA + glycerol
Marasmus: “normal” response to starvation
♣ Muscle- inc utilization of triglycerides/FAs
♣ Brain: inc utilization of ketones (dec glucose)
♣ Liver: dec gluconeogenesis
♣ Muscle: dec protein degradation (very high inc recycling AA, but continues, esp skeletal muscles)
♣ Liver/kidney: dec urea prod and excretion
♣ Result: utilization of fat stores, minimize muscle wasting dec BMR
“nl” response to starvation
♣ dec physical activity/inc resting
♣ dec BMR- hypothermia, hypotension, bradycardia
♣ endocrine changes: dec inuslin, dec thyroid, inc EPI, and inc corticosteroids
♣ GI: mucosal atrophy, dec seretions, dec motility
♣ Myocardial atrophy, dec CO
♣ Loss of functional reserve and physiologic responsiveness to stress
managing protein energy malnutrition
go slowly!!
resolve life-threatening conditions/infections
restore nutritional status w/o abruptly disrupting homeostasis/adapted state
ensure nutritional rehabilitation
referring syndrome
metabolic consequences due to rapid reinstitution of nutrients (and E/substrate) in pt w/ PEM
can result in sudden death
catabolic–> anabolic state
fluid shifts –> Hear failure
requires E, nutrients, enzymes
common derangements: K, Mg, P, thiamine
K- inc insulin secretion (in response to feeding) –> intracellular glucosee and K –> dec serum K–> altered nerve/muscle func
P- inc insulin –> intracellular P; inc intracellular phosphorylated intermediates (incl glucose)
P is trapped intracellularly, so dec serum P –> altered nerve/muscle func
Mg: inc requirement w/ inc metabolic rate (cofactor for ATPase)
Thiamine: rapid depletion (cofactor for glycolysis) w/ CHO –> cardiomyopathy +/- encephalopathy
management refeed slowly (start 50-75% basal needs) avoid fluid overload (enteral vs IV) monitor and supplement levels as necessary monitor vitals monitor PE (edema, rash) resolution of edema before full feeding
millennium development goals MDG 2000-2015
progress
less progress
successful because
Progress:
♣ Eradicate extreme poverty and hunger (down about 15%)
♣ Promote gender equality and empower women
♣ Reduce child mortality by 2/3
♣ Improve maternal health
Less progress
♣ Hunger, sanitation, environ sustainability
♣ Nutritional indicators requiring social and behavioral change
Successful because
♣ Repeated message: health is essential for development- required attention of heads of state
♣ MDG’s focused attn on short list of outcomes w/ broad appeal
♣ Annual measurement and reporting to media, civil society, and governments
♣ Donor organizations prioritized investments based on the MDG
Sustainable development goals SDG 2016-2020
Five P’s: people, planet, prosperity, peace, and partnership
17 goals and 169 targets
health- Goal #3
♣ “ensure healthy lives and promote well-being for all at all ages”
water, sanitation, poverty, gender equality = targets in other goals total of 23 health related targets
WHO 6 global targets for nutrition
♣ stunting ♣ anemia in women ♣ low birthweight ♣ overweight- no inc ♣ exclusive breastfeeding for first 6 mo ♣ wasting
who is at risk for malnutrition
babies
women of reproductive age
children under 5 yo
first 1000 days principle
critical window from pregnancy to first 2 yrs of life for child health
stunting happens almost immediately - low Z scores
—impaired linear growth but still able to gain weight and visceral adiposity- at risk for diabetes, metabolic dysfunc, etc
conceptual framework for malnutrition
layered system that has both short and long term consequences
at the top
♣ basic causes- ineffective or unstable government/programs, poor infrastructure
• poor roads, lack of electricity isolation
• limits markets, access to resources- start with roads
underlying causes
♣ poverty, inadequate care, house environment, lack of health services, household food insecurity
♣ no electricity, running water, indoor air pollution
♣ few meds, no micronutrient supplements
♣ few trained professionals and resources
♣ lack of sanitation, clean running water
immediate causes
♣ disease, inadequate dietary intake
♣ monotonous diet, food insecurity
all lead to maternal and child undernutrition
♣ short term consequences: mortality, morbidity, disability
• 3.1 Million deaths/yr in under 5 yo’s
♣ long term consequences: adult size, intellectual ability, economic productivity, reproductive performance, metabolic and CVD
maternal child under-nutrition
o maternal undernutrition BMI <18.5
o 10-19% women
o underweight, and short stature = independent risk factors for poor reproductive outcomes
o many die in childbirth, and undernutrition greatly inc this risk
o women and transmission of stunting
♣ maternal height correlated w/ infant length
♣ major predictor of Length Z LAZ score at 3 mo: newborn LAZ score
scope of malnutrition problem
undernourished children
invisibility of malnutrition
what does poor health reflect?
undernourished children
♣ dec resistance to infection
♣ inc mortality from common ailments
♣ for survivors, each illness saps nutritional status vicious cycle
invisibility of malnutrition
♣ ¾ of children who die:
• are mild-moderately undernourished
• have no outward signs of illness or vulnerability- “hidden hunger”
what does poor health reflect ♣ wasting ~ acute E deficit ♣ stunting • chronic malnutrition, not the same as E deficit • micronutrient deficiencies (Zn, I, Fe, etc) • inflamm, recurrent infection • intergenerational effects • Rural > urban; M > F
childhood weight status
“obese” >95th percentile correlates well
“overweight” 85th-95th percentile correlation fair (~50% specific)
BMI = weight status <5th percentile underweight 5-85 healthy weight 85-95 overweight >95 obese >99 severely obese, w/ comorbidites; ~4% of US population (AHA translates this to BMI >35, or >120% of 99th%ile)
early rebound on growth chart is early predictor of obesity
demographics of obesity epidemic
at same BMI, AA children tend to have less body fat; Asian children tend to have more body fat
nonhispanic Whites are lowest prevalence across age range
black and latino children have higher
American indian children have highest rates of BMI/obesity across country
-varies by gender
obesity is increasing, but has plateau’ed somewhat
higher prevalence groups: older children--> adolescents native american, black, latino low socioeconomic status --maternal education
major co-morbidites w/ obesity
psychosocial
depression/anxiety (bullying)
eating disorders (binging/purging)
pulmonary
SOB, DOE, setting you up for HF,
obstructive sleep apnea (snoring, AM HA, fatigue, poor sleep),
obesity hypoventilation syndrome (dyspnea, edema, somnolence- hyperemic respiratory drive, so can’t give them oxygen- give them positive P)
renal
GI
NAFLD (commonly asymptomatic, high ALT, steatohepatitis)
GERD
gallstones (occur after rapid weight loss
gallstones
MSK
SCFE slipped capital femoral epiphysis (usually bilateral, pain)
Blowout’s disease (stress injury to medial tibial growth plate, often painless, bowed legs)
neuro pseudotumor cerebri (severe HA, often worse in AM, papilledema)
CVS -70% obese kids have >2: high LDL, low HDL high BP insulin resistance increased mortality in adulthood the more risk factors you have, the more fatty streaks you have in vessels
endocrine
impaired glucose metabolism (acanthosis nigricans)
T2DM
PCOS- abnl bleeding pattern, hyperadnrogenism (severe acne, hirsutism)
Hypothyroid (cold intolerance, coarse feat’s, thin hair, constipation)
key assessment component of obesity
plot BMI at least yearly >2yo
assess- diet and activity
FHx (CVD risk factors, obesity)
lifestyle
activity- 60min moderate per day for everyone
sedentary- max 1 hr for 2-5yrs; <2hrs for older kids
inadequate sleep (excess weight gain)
FHx- severe disability, some genetics, CVD, hypothyroidism, psych (eating disorders)
ROS for comorbidities
Vitals/PE
labs:
ALT, Vit D
lipids: screen in all kids once 9-11yo and again 17-21 yo
A1c: start after 10yrs or Tanner 2
conversation w/ family about obesity
communicate w/ families- avoid the word “obese”
-stigmatizing as fat and non-motivating
motivating and non-stigmatizing terms: “unhealthy weight” “Unhealthy BMI”
discuss avoidable health risks w/ parents: T2DM HTN carotid atherosclerosis dislipidemia arthritis, colon and breast cancer
discuss w/ child QOL issues: sports, energy, confidence, clothing
prevention and tx principles for obesity
staged model- prevention plus (primary care) structure weight management multidisciplinary weight management tertiary care (highly structured, surgery, met)
motivational interviewing
- elicit behavior change by exploring and resolving ambivalence
- pts perception of your empathy is important
- *reflections- make them think again**
bariatric surgery-
bypass or sleeve gastrectomy
tx basics -involve family clean up home environment negotiate 1-2 specific changes at a time make plan to MONITOR CHANGE -accountability, awareness, pos feedback, plan rewards system
currently available options of obesity tx
not effective --> effective accept weight where it is diet/exercise 3-10% weight loss drugs 5-12% medically supervised combo of diet + drug 10-15% surgery 15-30%
diet, exercise, behavior therapy indicated w/ BMI>25
pharmacotherapy >30 or >27 w/ comorbidity
surgery >40 or >35 w/ comorbidity
meds that may cause weight gain
anti-diabetic meds:
sulfonylureas
insulin
TZDs
mood stabilizers, antipsychotics
birth control pills: Depo Provera
glucocorticoids: prednisone
pharm tx of obesity
current meds 5-12% weight loss
benefits only last as long as pt takes the med.
-chronic tx likely needed
drugs probably not paid for by insurance so cost is big issue for pts
FDA approval, long term safety, efficacy conversation
choice of mech’s, OTC vs prescription, combinations
Phentermine
most widely prescribed anti-obesity drug
-no evidence of serious longterm side effects when used as single drug
inc NE content in brain
chemically related to amphetamine, “not addictive”
does 15-37.5mg/day
cost: $15-25/month (CHEAPEST)
FDA approved for only 3 months use
5-8% weight loss
side effects: HTN, HA, nervousness
orlistat (Xenical)
SAFEST weight loss med
approved for long term, OTC form
may be useful in those w/ poorly controlled HTN or psych problems
5-8% weight loss
pancreatic lipase inhibitor
-inhibits fat abs by 30%
120mg 3x/day
$100/month
GI side effects: oily stools, urgency
multivitamin to prevent fat soluble vitamin deficiency
Lorcasarin (Belviq)
serotonin 2C receptor agonist
previous serotonin agonists fenfluramine and dexfenfluramine caused cardiac valve disease, removed from market
2C receptor only in the brain not heart
4-5% weight loss
LEAST SIDE EFFECTS: minimal HA, dizziness, nausea
$220/month
unclear if physicians will prescribe off label w/ phentermine (no data on safety or efficacy)
Phentermine/Topiramate
combination gives greater efficacy w/ fewer side effects
doses 7.5/46 mg and 15/92mg phentermine/topiramate
$150/month
side effects: dry mouth, paresthesias, insomnia, dizziness, anxiety, irritability, disturbance in attn
risk of birth defects:
women need pregnancy test on starting and monthly while using
reduces BP, glucose, insulin, triglycerides, and raises HDL
unclear if physicians will prescribe off label using generic phentermine and topiramate
MOST EFFECTIVE 10-12% weight loss
Naltrexone SR/ Buproprion SR
8/90 tablets, 2 BID
INTERMEDIATE IN EFFECTIVENESS AND SIDE EFFECTS
worrisome side effects:
inc BP and pulse, lowers seizure threshold, suicidal ideation (black box)
common side effects: nausea, constipation, diarrhea, HA, dry mouth
category X in pregnancy
$200/month
stop if clinically sig inc in BP
stop if <5% weight loss at 3 months (goes for all weight loss drugs)
summary of medications
Xenical
Phentermine
Phentermine/topiramate
Xenical
safest option, but limited weight loss, costly
Phentermine
less expensive, most prescribed
not FDA approved for long term
Phentermine/topiramate
most effective
costly
Lorcasarin
only modestly effective,
least side effects
naltrexone/bupropion
intermediate effectiveness
obesity surgeries
in order of least to most effective and risky
lap band
sleeve gastrectomy
gastric bypass
lap band
20% weight loss
low mortality
few complications
sleeve gastrectomy
25% weight loss
0.1% mortality
relatively more complications
gastric bypass 30% weight loss 0.2% mortality 10% have some complication, but usually not serious -nearly eliminates Ghrelin
benefits of weight loss surgery
25% weight loss out to 20 yrs
only 5-10% regain all the weight
reduction in mortality after 1st year
- less CAD, CANCER (esp breast)
- diabetes/glucose reduction: HbA1c after 1 yr dropped to <6% in 42% of pts (vs 0% below 6% who saw an endocrinologist)
sleep apnea
HTN improved in half
GERD
urinary incontinence improvement
who is good candidate for surgery
BMI >35 w/ co-morbidites or >40
20-60yo
comorbidites: diabetes, sleep apnea, GERD, HTN, DJD
failed other forms of therapy
no serious active cardiac, pulm, or psych disease
risks of bariatric surgery
bypass death 0.7% w/in 30 days
late death 2-3% within 2yrs
failure to produce weigh loss: 10-15%
pulm embolus
anastomotic leaks/sepsis
thiamin deficiency: early, vomiting, Wernicke Korsakoff
B12 deficiency 30% complication rate
Fe deficiency, esp menstruating women
Ca/Vit D deficiency: osteoporosis
anastomotic ulcers or strictures with GBPS
cause bleeding or Fe deficiency anemia, nausea, vomiting
band erroioin/slippage w/ lap band
depression: 20% may last 3-6months
avoid pregnancy for at least 1 yr
folate deficiency: one prenatal
bariatric surgery summary
most effective tx we have for obesity
best tx we have for T2DM
changes appetite, doesn’t just restrict food intake
risk isn’t trivial but falling w/ improved methods
needs lifelong F/U
conversations for motivating healthy habits
the manager is the pt- he has the ultimate decision making capacity and authority
you are the consultant/coach
-expert, advisor
not in control, no authority
good listener, problem solver
key elements of effective counseling
ultimately the behavior change needs to come from pt
pt must see compelling need to change
pt must feel confident that can/will do what’s suggested and that proposed change will help
be empathetic and demonstrate it
general approach
understand pt’s beliefs and motivations
-you have to redirect existing motivation, you can’t create it
always look to put ball in pt’s court
avoid temptation to give advice
when in doubt, reflect back what pt said
try to steer convo towards measurable goals
general strategy ask to engage pt in convo listen to response reflect their answer empathize
behavioral models
transtheoretical model (stages of change)
health belief model
values based counseling
motivational interview
cognitive behavioral therapy
transtheoretical model
time ordered steps leading to sustained behavior change
decision making process
relies on self report
stages of change: pre contemplative contemplative planning action (person sees need for change, may have own idea of what they want to do) maintenance relapse? identification -your goal is to help person to the next stage
health belief model
person’s willingness to change relates to perception of vulnerability for illness and the possible effectiveness of tx
behavior changes occur if person:
perceives themselves as at risk for illness
IDs the problem as serious
convinced that tx is effective and not overly costly
exposed to cue to take health action
have confidence that they can perform specific behaviors that will be helpful
compelling need for change core values:
maybe health is not top priority
putting diet below other important priorities
core values for men:
wealth, adventure, achievement, pleasure, respect family, fun
core values for women:
family, independence, career, fitting in, attractiveness, knowledge, self control
can you link health behavior and core values?
motivational interviewing
examination and resolution of ambivalence is its central purpose
direct persuasion is not effective method for resolving ambivalence**
readiness to change/resistance provide feedback about the counselor’s demands
build a sense of self-efficacy
goal is to have pt do most of talking
person needs to see compelling need to change
ask questions w/ 1-10 scale and reflect on that
why is it __?
what would it take to make it a 10?
many pts see problem but don’t feel confident/capable to change
ask what it would take to get a behavior change?
probably a 7
small changes
high likelihood of success that will build self-efficacy
concentrate goals that are measurable
cognitive behavioral therapy
focus on actually changing unwanted behaviors, not motivation
self monitoring: intake, emotions, thoughts, motivations
stimulus control: identify trigger events and deal w/ them
cognitive restructuring: change unhelpful thinking
set goals:
the more specific the better
small achievable goals are better than big/difficult ones
statin benefit groups
clinical ASCVD
LDL >190 without 2ndary cause
primary prevention
-diabetes, 40-75yo, LDL 70-189
or
no diabetes, 40-75yo, LDL 70-189, + 7.5% risk of CVD event in next 10 yrs
dx overweight and obesity
BMI = kg/ (height in m)^2
waist circumference- abdominal adiposity
Edmonton Obesity staging system 0 –> 4
BMI info
surrogate for measurement of body fat content
same calc for men and women
no frame adjustments
allows classification of pts as to degree of obesity
classifications <18 underweight 18.5-24.9 nl 25-29.9 overweight 30-34.9 obese Class 1 35-39.9 very obese Class 2 >40 extremely obese Class 3
relationship between BMI and % body fat
disadvantageS:
can’t distinguish between lean and fat mass
BMI may be less accurate in certain populations: elderly, ethnic groups, large muscle mass
waist circumference info
abdominal adiposity- independent predictor of risk for DM, HTN, CAD, and dislipidemia
WC correlated w/ abdominal fat mass
used w/ BMI to identify risk groups
in risk:
F >=35”
M >=40”
around iliac crest, NOT belt size
proposed mech
release of FFAs into blood go to liver, causing insulin resistance
-FFA from intra-periotenal fat
inc VAT correlated w/ insulin resistance only if there are inc intrahepatic triglycerides
-neither omentecomy nor liposuction in human seems to improve insulin sensitivity
-if healthy obese people have nl metabolic labs, they’re at inc risk for becoming unhealthy
obesity rates in US
still increasing
many states >25% obese
much lower prevalence for asians
socioeconomic status- related to obesity, but main diff tends to be race/ethnicity, rather than socioeconomic
medical complications of obesity
affects every organ system in some way
T2DM
DM risk begins to inc at BMI >21-23
90% of pts who develop T2D have BMI >=23
HTN
linear w/ HTN and BMI
85% HTN pts occurs in BMI >25
obstructive sleep apnea
40% prevalence among obese
linked to other systemic problems
cancer
overweight/obesity assoc w/ inc risk of many cancers
obesity and mortality
-risk seems to inc around BMI 30
physical activity mitigates risk of obesity
characteristic of metabolic syndrome and defining levels
abdominal obesity
- Men >102 cm / 40”
- Women >88 cm / 35”
Triglycerides >150
HDL
Men <40
Women < 50
BP
>130/85
Fasting glucose >110 (now >100)
having 3/5 means you have metabolic syndrome
possible causes of obesity
long term positive E balance
-E intake -fat stores - E expenditure
gene-environment and pathogenesis of obesity
-2 genetically identical populations had very diff BMI’s based on environment
changing environment
-intake moe and expend less
unhealthy diet has inc more than healthy foods
walking has dec over yrs
how to evaluate pts w/ obesity
initial office visit:
eval potential obesity-related diseases in Hx, PE, labs
weight, weight loss history, eating, activity behaviors
-Calc BMI, categorize weight status
search for triggering factors, incl meds
-steroids, antipsychotics, anti-epileptics, anti-depressants, insulin, BBs
hypothyroidism, Cushing’s
congential- Prader Willi, Down Syndrome
Hypothalamic disorders: trauma, tumor, surgery
determine readiness to lose weight
-motivation, stress level, psychiatric issues (severe depression), time availability, meals, self-monitoring
initiate tx plan (incl other med professionals)
discuss goals and expectations
arrange F/U and support
appropriate office environ for obese pts (chairs w/ no arms, positive environment)
obese pts tend to have unrealistic goals- talk them down
even 5-10% weight loss improves risk factors
obesity tx pyramid
BMI >25 lifestyle modification
BMI >30 pharmacotherapy
BMI >25 consider surgery
strategies for obesity tx
food strategies
food diaries
fat gram budge (avoid high-E density foods)
meal replacements (comprehensive w/ all nutrients)
dec portions
dec E density
diet books/commercial programs (self help diets w/ BALANCED macronutrients tend to be more sustainable)
non-food strategies
dec tv time
sleep
neighborhoods, social environ (food deserts)
macronutrient content of diet layout
55% carbs
15% protein
<30% fat
low fat tends to mean lower calorie
mediterranean or low carb diet better at yrs than low fat diet
low fat, low carb diet: no sig diff at 2 yrs
macronutrient content didn’t affect weight loss at 2 yrs- pick something they’ll stick with
weight loss management
create E balance at reduced body weight
physical activity is essential** for weight loss MAINTENANCE success
- doesn’t help weight loss
- helps change body composition, helps improve appetite regulation, CV health, BP,
- preserves fat-free mass
combined aerobic and resistance activity
-30min/day moderate activity
60min/day to prevent weight regain
2008 physical activity guidelines for Americans
Adults 18-64
aerobic
150min/week moderate or
75 min/week vigorous
additional benefits w/ increasing to 300min/week
muscle strengthening should be at least 2x/week
children 6-17
1hr or more every day moderate or vigorous
vigorous at least 3x/week
muscle/bone strengthening at least 3x/week
behaviors of successful long-term weight management
self monitoring
diet: food intake diary, limit certain foods/quanitty
weight: check body weight >1/week
low cal, low fat
total E intake 1300-1400
E intake from fat 20-25%
eat breakfast
regular physical activity 2800kcal/week
limit TV <2 hrs/day
losing weight and keeping it off-
biological component
Ghrelin (hunger hormone) levels are INCREASED 1 yr after starting weight loss
genetics and environment in obesity
genetics play a role, but hasn’t changed significantly in last few decades
environment- main cuprit
feedback mechanism are designed to protect against undernutrition
adaptations occur in response to overeating
- less weight gain than expected from total calories ingested
- sig individual variation
- adaptation exists to varying degre
physiologic and non-homeostatic mechs for E balance regulation
physiologic/homeostatic
-short term signals: meal related
long term signals: adiposity related
non-homeostatic mechs: reward and motivation cognitive/executive decisions environmental cues social context
E homeostasis- anabolic vs catabolic
anabolic pathways tell us to EAT
inhibit E expenditure
positive E balance
weight gain
catabolic pathways inhibit eating
activate E expenditure
neg E balance
weight loss
at some point when you get enough adipose tissue buildup, it sends signals to activate catabolic and inhibit anabolic pathway to balance out the E balance
hypothalamus and lateral nucleus
important hunger center
activated by Ghrelin
inhibited by leptin
LN ablation: dec food intake
if you Zap lateral- you shrink laterally
hypothalamus and ventromedial nucleus
important satiety center
activated by leptin
VMN ablation: inc food intake
if you Zap VM area, you’ll grow ventrally and medially
leptin hormone
released from adipose tissue
feeds back to brain and stimulates catabolic and inhibits anabolic pathways to regain E balance
insulin works in similar way
arcuate nucleus
NPY neurons = hunger neurons
accurate nucleus is stimulated, releases NPY, go to NPYR to activate anabolic (inc food intake)
-also releases AgRP which inhibits catabolic pathways
POMC neurons = release alpha-MSH, go to MCR to activate catabolic pathway (dec food intake)
leptin and insulin inhibit anabolic (NPY) and stimulate catabolic (POMC, alpha-MSH)
meal to meal regulated signals
Ghrelin and others
Ghrelin hormone
hunger hormone,
stimulates anabolic pathways- stimulates NPY and AgRP
PYY, GLP-1, CCK, released by GI when eating
inhibit anabolic pathways
concept of set point and homeostatic regulation
obese prone OP pts have much higher levels of leptin, but hunger level is the same
-leptin resistance??
biological signals primary designed to protect during times of undernutrition
perhaps it’s about “resistance” to hormones?
or more complicated
non-homeostatic regulation of E intake
internal inputs: reward mechs, cravings, thinking about food restraint learned behaviors attn
external inputs environmental cues availability/portions social context time cues
when hungry: hedonic foods > basic objects
-brain region for reward, visual cortex light up
obese resistant vs obese prone pts: fast vs fed
Insula is major player
at fed state: OR pt insula shuts off, but OP pt increases insula light-up
—can turn off insula w/ exercise- brain is plastic
