Unit 2-2 Metabolic (Protein and Diet) Flashcards

1
Q

AA basics and categorization

A

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

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2
Q

protein breakdown process
-enzyme type
process
2 breakdown pathways

A

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)

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3
Q

transamination process

A

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

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4
Q

urea cycle process

A

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

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5
Q

glutamine and arginine significance w/ N

A

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

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6
Q

special AAs
sulfur containing- 2
aromatic AAs- 3

A

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

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7
Q

scurvy
define
signs/symptoms
Vit C role

A
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

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8
Q

Vitamin C, K, B6 cofactors

A

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
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9
Q

proteases

A

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

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10
Q

urea cycle and control points

A

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

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11
Q

transport of ammonia through he blood

A

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

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12
Q

Arginine in nerve and muscle func

A

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

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13
Q

hyperammonemia

A

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

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14
Q

Maple syrup urine disease MSUD

A

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

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15
Q

thyroid chemistry

A

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

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16
Q

Heme metabolism
porphyrias
degradation
jaundice

A

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)

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17
Q

cysteine

A

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

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18
Q

Methionine

A

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

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19
Q

hyperhomocysteinemia

A

multiple problems incl CVD
from low folate, B6, and B12 (vascular disease)

cysteine is now essential

Tx w/ folate, B6, B12

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20
Q

homocystinuria

A

(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

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21
Q

cystinuria

A
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)

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22
Q

vascular disease

A

autoimmune disease where Hcy acts as a pro-inflammatory molec

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23
Q

B6, B12, folate in Cys and Met metabolism

A

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

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24
Q

Trp metabolism products

A

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

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25
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
26
Tyrosinemia
defect in multi-step tyrosine degradation 3 types, depending on particular dysfunctional enzyme involved
27
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
28
BH4 cofactor uses
first degradation Phe: phenylalanine hydroxylase Tyr: tyrosine hydroxylase Trp: tryptophan hydroxylase
29
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 ```
30
ribose naming
ribonucleo: base: AGCUT (I, orotic) side: base + sugar tide: phosphate
31
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
32
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
33
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 ```
34
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
35
pyrimidine breakdown
C and U have similar pathways lead to malonyl CoA and acetyl CoA ends up as succinyl CoA
36
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
37
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)
38
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
39
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
40
drugs that target nucleotide metabolism
drugs that slow nucleotide synthesis are effective against viruses, bac, and cancer cells that are rapidly dividing
41
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%
42
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
43
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
44
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? ```
45
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)
46
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
47
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
48
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 ```
49
Sandhoff disease
AR inhertiance looks like Tay Sachs but has HSM AND bony disease both beta-hexosaminidase A (Tay Sachs) and B HSM
50
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
51
Niemann-Pick disease
AR inheritance ``` sphingomyelinase supra nuclear gaze palsy cherry red spot** on macula BIG HSM lipid-laden macrophages- "foam cells" ```
52
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
53
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)
54
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
55
McArdle disease
AR inheritance Glycogen phosphorylase muscle cramping after exercise myoglobuinuria (coffee colored urine after exercise)
56
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
57
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
58
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
59
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
60
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
61
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
62
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
63
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)
64
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
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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 *
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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**
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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
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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
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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
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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
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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
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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)
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anthropometrics
lenght/height weight waist circumference etc reflect growth and dev pediatrics: use growth charts adults: BMI
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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 ```
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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)
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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 ```
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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
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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
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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 ```
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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 ```
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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
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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 ```
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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 >>> 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 ```
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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
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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
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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
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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 >>> 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
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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
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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
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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 ```
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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
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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
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starvation
pure caloric deficiency | host adapts to conserve lean body mass and inc fat metabolism
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cachexia
associated w/ inflammatory or neoplastic conditions | not reversed by feeding: anorexia
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sarcopenia
subnormal amount of skeletal muscle, w/o weight loss
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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)
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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
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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
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managing protein energy malnutrition
go slowly!! resolve life-threatening conditions/infections restore nutritional status w/o abruptly disrupting homeostasis/adapted state ensure nutritional rehabilitation
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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 ```
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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
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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
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WHO 6 global targets for nutrition
``` ♣ stunting ♣ anemia in women ♣ low birthweight ♣ overweight- no inc ♣ exclusive breastfeeding for first 6 mo ♣ wasting ```
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who is at risk for malnutrition
babies women of reproductive age children under 5 yo
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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
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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
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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
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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 ```
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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
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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 ```
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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)
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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
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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
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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 ```
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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
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meds that may cause weight gain
anti-diabetic meds: sulfonylureas insulin TZDs mood stabilizers, antipsychotics birth control pills: Depo Provera glucocorticoids: prednisone
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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
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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
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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
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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)
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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
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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)
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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
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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 ```
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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
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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
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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
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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
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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
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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 ```
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behavioral models
transtheoretical model (stages of change) health belief model values based counseling motivational interview cognitive behavioral therapy
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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 ```
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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?
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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
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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
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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
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dx overweight and obesity
BMI = kg/ (height in m)^2 waist circumference- abdominal adiposity Edmonton Obesity staging system 0 --> 4
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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
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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
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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
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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
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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
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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
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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
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obesity tx pyramid
BMI >25 lifestyle modification BMI >30 pharmacotherapy BMI >25 consider surgery
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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)
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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
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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
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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
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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
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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
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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 ```
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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
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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
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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
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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
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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)
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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
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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
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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