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DEMS > Unit 3 > Flashcards

Unit 3 Flashcards

1
Q

Describe how proteins are broken down to AAs in the gut and tissues

A
  • proteins are broken down by peptidases that are activated in the gut into AAs –> absorbed –> enter circulation
  • two pathways for breakdown: ubiquination and lysosomes
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2
Q

Describe the flow of nitrogen from an AA to urea

A
  • AA donates an NH2 to an alpha-ketoglutarate (by AT) to make L-glutamate + keto acid
  • released as NH3 from glutamate, which regenerates the alpha-ketoglutarate
  • urea cycle occurs in liver
  • glutamate, NH3, and aspartate enter urea cycle
  • NH3 from transamination –> carbamoyl phosphate by carbamoyl phosphate synthase 1 (RLS)
  • nitrogen in carbamoyl phosphate enters urea cycle, combines with NH3 from aspartate to make urea
  • urea is peed out
  • AA+alpha-kg –> glutamate + alpha-keto acid –> NH3 –> urea cycle –> urea
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3
Q

List soem of the special issues assoc w sulfur containing, gluconeogenic, ketogenic, branched chain, and aromatic AAs

A

1) sulfur containing:
- cysteine and methionine
- disulfide bridges
- S-adenosylmethionine is important energy source for wound healing, vascular disease, and B12
- glutathione containse cysteine and is protective agaisnt ROS

2) branched chain:
- require special enzymes for breakdown
- def can lead to MSUD

3) aromatic:
- precursors for 5HT, niacin, dopamine, NE, epi, tetrahydrobiopterin, and thyroid hormone

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4
Q

Ways to categorize AAs

A

1) chemical properties:
- acidic/basic
- polora/non-polar

2) synthesis ability of body:
- essential: body can’t make
- non-essential: body can make
- conditionally essential: limited capacity for body to make

3) chem constituents:
- sulfur containing
- nitrogen side chain
- branched chain
- aromatic

4) energy needs:
- glucogenic: for gluconeogenesis
- ketogenic: make acetylCoA –> make ATP through TCAC or make ketones

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5
Q

Pathways for protein degradation

A

1) ubiquination in proteasomes

2) lysosomes

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6
Q

Pathways for protein degradation

A

1) ubiquination in proteasomes

2) lysosomes

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7
Q

Transamination

A
  • for gluconeo, NH2 of AA needs to be removed
  • for carbon skeleton to AA, need to add NH2
  • bidirectional
  • in liver
  • AA donates NH2 to alpha-ketoglutarate –> L glutamate and alpha-keto acid (catalyzed by aminotransferase) –> NH3 released and alpha-ketoglutarate made again
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8
Q

Urea cycle

A
  • NH3 from transamination converted to carbamoyl phosphate from carbamoyl phosphate synthase 1 (RLS)
  • CP enters urea cycle and combines with NH3 from aspartate –> make urea which is peed out as urea nitrogen
  • urine nitrogen as urea measures AA catabolism
  • glutamine accepts N from other AAs –> brings to liver and kidney and donates to glutamate –> alpha-ketoglutarate (catalyze by glutamate dehydrogenase) (RLS)
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9
Q

Recognize the 20 AAs and list examples of post-translational mods

A
  • each AA has their own tRNA
  • examples:
    1) collagen: triple helix with hydroxyproline and hydroxylysine
  • Hyp –> H-bonding in collagen to inc strength; prolyl hydroxylase converts Pro to Hyp
  • Hyl –> crosslinks; lysyl hydroxylase coverts Lys to Hyl
  • PH and LH rely on vitC

2) g-Carboxyglutamate (Gla): target proteins to membranes via Ca chelation
- G-glytamyl carboxylase converts Glu to Gla and required vitK

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10
Q

Describe scurvy

A
  • vitamin C deficiency –> reduced collagen strength because of failure of post-trans mods of Hyp and Hyl
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11
Q

Describe cellular aspects of protein degradation and proteases involved in protein degradation

A

1) ubiquitin-proteasome:
- ATP-dep
- crosslink protein to ubiquitin –> sequestered to proteasome that has proteolytic activity

2) lysosome:
- ATP-indep
- engulf EC proteins
- broken down by acid hydrolysis

  • proteases are in proenzyme form usually
    1) pepsinongen –> pepsin by HCl to cleave proteins
    2) enteropeptidase cleaves trypsinogen to trypsin
    3) trypsinogen cleaved to trypsin –> cleaves all other zymogens in SI (chymotrypsinogen, procarboxypeptidase)
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12
Q

Describe transamination and list liver damage markers

A
  • aminotransferase transfers amino groups
  • converts alpha-keto acid to corresponding AA and also does reverse
  • Keq is about 1
  • reversible
  • 100s of ATs for 20 AAs
  • ATs move N to Asp and NH3 for urea cycle
  • alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
  • PLP (pyridoxal phosphate) is a derivated of vitB6: used by ATs to hold/transfer amino groups
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13
Q

Describe the control points for the urea cycle

A
  • carbamoyl phosphate synthase1 (CPS1)

- N-acetyl glutamate (formed by N-acetylglutamate synthase act by arginine) act CPS1

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14
Q

List the means of NH3 transport in the blood

A
  • cannot be transported in blood, so rely on urea
  • glutamine holds 2 NH3 groups
  • GDH is a control pt for protein metabolism to remove N or add to AAs
  • glutamine synthase converts glutamate to glutamine for transport to liver and entry into urea cycl
  • in muscle, use alanine instead of glutamine for transport in alanine-glucose cycle
  • in muscle, pyruvate –> alanine by transamination and in liver, alanine –> pyruvate by transamination and use it for gluconeo
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15
Q

Explain the difference between ketogenic and glucogenic AAs

A
  • depends on outcome of keto acid
  • glucogenic: makes pyruvate or TCAC intermediates (OAA from aspartate transam)
  • ketogenic: no net prod of glucose (lysine and leucine breakdown gives acetylCoA)
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16
Q

Describe urea cycle disorders, hyperammonemia, MSUD

A

Hyperammonemia:

  • elevated NH3 in blood due to UC enzyme defects –> inhibition of TCAC
  • encephalopathy, coma, death
  • asterixis
  • limit protein intake
  • give lactulose and trap NH4

MSUD:

  • inc BCAAs (leucine, valine, isoleucine)
  • BCAA –> deaminated to alpha-keto acid –> decarboxylated to succinlCoA or acetylCoA
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17
Q

Describe thyroid chemistry and understand how thyroxin is produced

A
  • tyrosine makes T4 which is converted to T3
  • TSH stimulated iodide uptake and stim release of T4 and T3
  • thyroid peroxidase: oxidizes iodide to I2
  • thyroglobulin: contains Tyr residues iodinated to form T4 and T3
  • Thyroxin binding globulin: transport T4 and T3
  • T4 (deiodinase) –> T3, which is a more active form of thyroxin with one less iodine
  • T4 and T3 transported from thyroid through blood via TBG
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18
Q

Describe heme metabolism and porphyrias

A
  • porphyrins are cyclic molecules of 4 pyroles made in liver
  • pyrole –> bilirubin –> porphyrin
  • bind Fe2+
  • porphyrin synthesis:
    1) gly + succinylCoA –> gamma-aminolevulinic (ALA) acid (by gamma-aminolevulinate synthase)
    2) 2xALA –> porphobilinogen (by gamma-aminolevulinate dehydratase)
    3) porphobilinogen ———> protoporphyrin 4 (by 4 enzymes)
    4) protoporphyrin 9 –> heme (by ferrochelatase)
  • lead inhibits gamma-aminolevulinate dehydratase and ferrochelatase
  • degradation: heme –> biliverdin (green) –> bilirubin (red orange) –> bilirubin diglucuronide –> urobilinogen –> stercobilin (brown)
  • bilirubin is transported bia albumin to the liver where it is conjugated with glucuronic acid –> bilirbuin diglucuronide (conjugated bilirubin)
  • in intestine, bilirbuin diglucuronide is oxidized to stercobilin
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19
Q

Urea cycle components

A

1) ornitihine –> citrulline:
- by carbamoyl phosphate synthetase 1

2) cirtulline + aspartate –> arginosuccinate
- by argininosuccinate synthase

3) argininosuccinate –> arginate
- by argininosuccinate lyase

4) arginine –> ornithine + urea
- by arginase

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20
Q

Carbamoyl phosphate synthetase 1

A
  • found in mito
  • bicarb + NH3 –> carbamoyl phosphate
  • this rxn uses 2 ATPs
  • N-acetylglutamate allosterically activates CPS1
  • arginine activates N-acetylglutamate synthase which converts acetylCoA+glutamate –> N-acetylglutamate
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21
Q

Carbamoyl phosphate synthetase 1

A
  • found in mito
  • bicarb + NH3 –> carbamoyl phosphate
  • this rxn uses 2 ATPs
  • N-acetylglutamate allosterically activates CPS1
  • arginine activates N-acetylglutamate synthase which converts acetylCoA+glutamate –> N-acetylglutamate
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22
Q

Maple Syrup Urine Disease

A
  • when BCaKADHC is deficient –> build up of alpha-keto acids in urine
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23
Q

What are the 2 entry points of N into the urea cycle?

A

1) NH3 from glutamate by GDH –> free NH3 and an alpha-ketoglutarate; NH3 combines with CO2 to make carbamoyl phosphate
2) OAA converted to aspartate via transam and enters after citrulline

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24
Q

What is the key RLS of entry of N into the urea cycle and its allosteric activation?

A

Glutamate –> alpha-ketoglutarate + NH3 (by GDH)

  • act by ADP and GDP
  • inh by ATP and GTP
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25
Q

List the sulfur containing AAs

A

Methionine:
- essential AA
Cysteine:
- unessential AA

  • ## sulfur plays important role in disulfide bonds for membrane receptors
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26
Q

Describe the biological utility of Cys in regard to its ox state (alone or within GSH)

A
  • forms disulfides with other cys
  • GSH is a tripeptide that controls redox potential vis GSH –> GSSG where cysteine is important
  • the oxidized form makes disulfide bonds for structural integrity of proteins
  • reduced form occurs when bonds are broken
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27
Q

Describe Met, its relation to SAM and the energy provided in SAM

A
  • Met + ATP by SAM synthase –> SAM
  • met produces S-adenosylmethionine (SAM) which is high energy storage unit in the form of a methyl group
  • SAM produced in first step of methionine degradation –> converted to S-adenosylhomocysteine (SAH)
  • SAM is involved in methylation, epigenetics, etc.
  • SAM turns NE into epi and methylates cystein residues
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28
Q

Describe where vitamins are used in Cys, Met metabolism: Folate, B6, B12

A
  • B12 and THF in converting homocysteine to Met

- B6 in converting homocystein + serine –> cystathionine –> cysteine

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29
Q

List biologically important molecules derived from Trp metabolism

A
  • glucogenic and ketogenic

- makes serotonin (NTs), melatonin (hormone), niacin (vitamin)

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30
Q

Describe diseases related to Pre, Tyr metabolism: Phenylketonuria (PKU), tyrosinemia, parkinson’s, and the use of MAOis

A

a

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31
Q

Hyperhomocysteinemia

A
  • inc homocysteine levels –> lots of problems including CV disease
  • due to dec folate, B6, B12
  • Cys is essential
  • treat with folate, B6, B12
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32
Q

Homocystinuria

A
  • defect in cystathionine-b-synthase (CBS)
  • cannot convert homocysteine to cystathionine (and eventually cysteine)
  • mental retardation, osteoporosis, and vascular disease
  • cysteine is essential
  • treat with vitB6 to force CBS to work
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33
Q

Cysteinuria

A
  • kidney stones
  • due to defect in transporter of cysteine (and ornithine, lysine, and arginine) –> crystallization in urea
  • treat with acetazolamide which makes cysteine more soluble
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34
Q

Cysteinuria

A
  • kidney stones
  • due to defect in transporter of cysteine (and ornithine, lysine, and arginine) –> crystallization in urea
  • treat with acetazolamide which makes cysteine more soluble
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35
Q

Cofactors for transferring carbons

A
  • SAM

- THF from bacteria and folate

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36
Q

GSH as a redox buffer

A
  • GSH is very soluble
  • thiol acts as redox buffer to maintain proteins in reduced forms and regulate activity
  • cofactor for several enzymes
  • reduce H2O2 to H2O and general protection against ROS
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37
Q

Trp metabolism

A
  • Trp metabolized to pyruvate or acetylCoA
  • first hydroxylated by tryptophan hydroxylase using BH4 as a cofactor
  • Trp used to make 5HT, melatonin, and niacin
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38
Q

Phenylketonuria

A
  • defect in phenylalanine hydroxylase –> build up of byproducts (phenyllactate, phenylacetate, phenylpyruvate)
  • smell bad with phenylacetate
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39
Q

Tyrosinemias

A
  • defects in tyrosine degrad
  • 3 types
  • hydroxylation of tyrosine to catecholamines is ok, but decarboxylating aromatic AA is defective
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40
Q

Tyroseinemias

A
  • defects in tyrosine degrad

- 3 types

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41
Q

GSH as a reducing agent and SH buffer

A
  • GSH is a product of PPP/HMS
  • allows formation, breakage, and reformation of disulfide bonds for correct protein folding
  • GSH is more soluble than cys
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42
Q

THF

A
  • made during regen of Met from homocysteine
  • from vitB9
  • needed for synthesis of AAs and nucleic acids
  • SAM only donates methyl groups, but THF can donate CH2, CH=NH, and CH=O as well
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43
Q

Conversion of Met to homocystein back to met

A

met –> SAM (by SAM synthetase) –> SAH (by methyltransferases) –> homocysteine (by adoHcy hydrolase) –> methionine (by methionine synthase + B12+THF)

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44
Q

ID the sources of atoms in purine and pyrimidine bases, the key cofactors, and the sources of energy involved in de novo synth

A

Source of atoms:

  • purines: AAs - Glu, Gly, Asp; THF, CO2
  • pyrimidines: AAs - Glu, Asp; CO2

Cofactors:

  • purines: THF, ATP, CO2, AAs
  • pyrimidines: ATP, CO2, PPRP

Energy source:

  • purines: AMP and GMP (to make these requires GTP and ATP respectively)
  • pyrimidines: UDP and CTP (both require ATP)
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45
Q

List the key differences between the synth of purine and pyrimidine nucleotides

A

1) source of base:
- purines build base on sugar
- pyrimidines make base separately then add base to sugar

2) source of atoms:
- purines: Glu, Gly, Asp; THF, CO2
- pyrimidines: Glu, Asp, CO2

3) intermediates:
- purines: IMP –> GMP or AMP
- pyrimidines: UMP –> UDP –> UTP –> CTP

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46
Q

Name the key regulated steps and feedback loops within the de novo purine and pyrimidine synth and degrad pathways

A

Purine - regulated steps:

1) ribose 5’ phosphate –> PRPP
- catalyzed by PRPP synthase
- ribose 5’ phosphate from HMP
- act by Pi, inh by AMP, GMP, IMP

2) PRPP+glutamine –> 5 phosphoribosylamine
- catalyzed by glutamine phosphoribosyl pyrophosphate amidotransferase (GPPAT)
- IMP, GMP, AMP inh early enzymes
- act by PRPP

Pyrimidine - regulated steps:

1) 2ATP+CO2+glutamine –> carbamoyl phosphate
- catalyzed by CPS2
- act by PRPP and ATP
- inact by UTP, UDP
2) feedback:
- UMP –> UDP –> UTP –> CTP
- UTP inact CPS2

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47
Q

ID the enzyme that reduces ribose to deoxyribose, describe the regulation of this enzyme, and name its substrates

A
  • ribonucleotide reductase
  • substrates are diphosphates ADP, GDP, CDP, UDP
  • UDP –> dUDP –> dephos to dUMP –> dTMP by thymidylate synthase –> dTDP and dTTP by kinases; uses THF as cofactor
  • regulation: dATP turns off, ATP turns on
  • can specify which dNTP needs to be made
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48
Q

Describe how 5-fluorouracil and similar drugs inhibit nucleotide synth

A
  • 5-fluorouracil: pyrimidine analog that inh thymidylate synthase –> dec dTMP –> failure of cells to divide; anti cancer
  • methotrexate: folic acid analog –> inh dihydrofolate reductase –> dec dTMP and protein synth
  • 6-mercaptopurine: purine analog, inh AMP synth, block de novo purine synth
  • AZT: inhibit viral polymerase
  • acyclovir: target viral DNA polymerase and reverse transcriptase
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49
Q

Why is purine and pyrimidine synth important?

A

1) make DNA and RNA
2) make ATP and GTP
3) make CoA, FAD NAD, NADP
4) make cAMP, cGMP
5) make UDP-glucose for glycogen synth and CDP-diacylglycerol for glycerophospholipid synth

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50
Q

Purine nucleotide synthesis

A
  • start with ribose sugar and then build base on sugar
  • *key regulated step: at start when PRPP (which contains ribose) and glutamine are used by glutamine phosphoribosyl pyrophosphaye amidotransferase to add N to PRPP
  • second regulated step: conversion of ribose 5’-phosphate to PRPP
  • adds AAs and CO2 to growing base and also THF and ATP are important
  • first base produced is inosine monophosphate (IMP) –> used to make GMP and AMP
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51
Q

Pyrimidine nucleotide synthesis

A
  • base is not made on ribose sugar; made separately and then added to sugar
  • first step is catalyzed by carbamoyl phosphate synthetase 2
  • CPS2 is act by PRPP and inh by UTP
  • first molecule made is UMP then converted to UTP then converted to CTP by CTP synthase
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52
Q

Pyrimidine nucleotide synthesis

A

a

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53
Q

Changes in phosphorylation states and conversion of rNDPs to dNDPs

A
  • use kinases to convert NMP to NDP to NTP by taking phosphate from ATP
  • ribonucleotide reductase converts ribose to deoxyribose by operating on the NDPs
  • RR act by ATP and inact when dATP builds up
  • also sensitive to specific dNTPs
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54
Q

Changes in phosphorylation states and conversion of rNDPs to dNDPs

A

-

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55
Q

De novo synth of dTTP and dCTP

A

UMP –> UDP –> dUDP –> dUMP –> dTMP –> dTDP –> dTTP

also

UMP –> UDP –> UTP –> CTP –> CDP –> dCDP –> dCMP –> dUMP –> dTMP –> dTDP – dTTP

for dCTP:

UMP –> UDP –> UTP –> CTP –> CDP –> dCDP –> dCTP

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56
Q

Nucleotide degradation

A
  • consume a lot of nucleotides than we need so need to degrade and excrete
  • for purines: first remove base from sugar to have adenosine or guanine –> bases are further broken down to uric acid which is peed out –> problems can lead to diseases like gout and SCID
  • for pyrimidines: first remove base ring from sugar –> base ring is opened up (no uric acid) –> breakdown base ring to succinylCoA, malonylCoA, and acetylCoA –> water soluble so no problems like in purine degradation
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57
Q

Salvage pathways

A
  • reuse partially degraded nucleotides to make nucleotides

- takes free bases and attaches them to ribose sugar in the form of PRPP

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58
Q

SCID

A
  • sever combine immunodeficiency syndrome
  • mutation in gene encoding adenosine deaminase –> defect in purine degrad –> buildup of dATP –> inh ribonucleotide reductase –> prevent dNTP production –> affects rapidly proliferating cells most (lymphocytes, epithelial cells, mucous cells)
  • treat with gene therapy
  • occurs in kids
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59
Q

Gout

A
  • build up of uric acid in blood –> deposition of monosodium urate crystals in joints
  • usually due to underexcretion of uric acid
  • less common is overprod of purines
  • RFs: age, meat, seafood
  • see negatively birefringent yellow crystals under parallel light
  • result of purine degrad
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60
Q

Lesch-Nyhan syndrome

A
  • deficiency in one of the primary enzymes in purine salvage pathway (HGPRT) –> inc rates of de novo synth of purines and inc PRPP because defect in salvage pathway –> inc degradation –> see gout symptoms, self-mutilating behavior, and other mental probs
  • X-linked rec
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61
Q

Lesch-Nyhan syndrome

A
  • deficiency in one of the primary enzymes in purine salvage pathway (HGPRT) –> inc rates of de novo synth of purines –> see gout symptoms, self-mutilating behavior, and other mental probs
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62
Q

Drugs for nucleotide synth and degrad

A

1) methotrexate and 5-florouracil:
2) 6-mercaptopurine:-
3) azidothymine (AZT):
4) cytosine arabinoside (araC)
5) acyclovir (ACV)
6) acivicin

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63
Q

methotrexate and 5-florouracil

A
  • targets thymidylate synthase/folate metabolism cycle

- anti cancer

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64
Q

6-mercaptopurine

A
  • inh AMP synth

- anti cancer

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65
Q

azidothymine (AZT)

A
  • inh viral polymerase

- anti HIV

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66
Q

cytosine arabinoside (araC)

A
  • targets DNA polymerase

- anti leukemia

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67
Q

acyclovir (ACV)

A
  • targets viral DNA polymerase and reverse transcriptase

- anti HSV

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68
Q

acivicin

A
  • Gln analog
  • inh nucleotide synth, mostly GMP
  • anti cancer
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69
Q

PKU

A
  • def of phenylalanine hydroxylase –> build up of phenylalanine –> irreversible intellectual disability
  • AR inheritance
  • 6Ms: microcephaly, (epilepsy), mentally retarded, mischievous, musty body odor, dec myelin formation, dec monoamines
  • diagnosis: newborn screening (BIA, flurometric, MS) for inc phenylalanine >120 and normal BH4
  • management: low protein diet and restrict phe, BH4 supplement; supplement with LNAA transporters; prevent in pregnant women
  • symptoms: microcephaly, epilepsy, intellectual disability, behavior problems, musty body odor, eczema
  • dec melanin, dec catecholamine synth
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70
Q

Maple Syrup Urine Disease

A
  • maple syrup odor in cerumen/urine after birth
  • inc BCAAs due to def degradation (def BCKAD)
  • ketonuria
  • irritability, lethargy, neuro problems
  • poor feeding in 2-3days
  • diagnosis: clinical features, dec BCKAD, inc BCAAs and alpha-keto acids, genetic testing
  • management: dietary restriction of BCAAs, give sufficient calories, insulin, AAs for protein synth, thiamine supplement
  • AR inheritance
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71
Q

Tyrosinemia type 1

A
  • young infants
  • liver problems in 1st year, renal problems, growth failure, rickets
  • neuro probs, neuropathy, abd pain, resp failure
  • treat with nitisinone and low tyrosine diet, dec intake of phe and tyr, liver transplant for children
  • due to def of FAH
  • see inc succinylacetone in blood and urine
  • inc tyr, met, phe in plasma
  • inc tyr metabolites and gamma-ALA
  • genetic testing for FAH mutations
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72
Q

Classical homocystinuria

A
  • caused by defect in CBS
  • see intellectual disability, myopia, skeletal abnormalities, thromboembolism
  • marfanoid habitus
  • prone to bone problems
  • diagnosis: inc plasma homocystine, total homocystine, homocystein-cysteine mixed disulfide, and met
  • inc urine homocystine
  • dec CBS activity
  • genetic testing for CBS mutations
  • management: dec met, inc cysteine, inc B12 and folate, give B6 if responsive
  • control homocysteine concentrations and prevent thrombosis
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73
Q

Urea Cycle Disorders

A
  • defect in enzymes lead to accumulation of NH3 in first few days of life
  • rapidly develop cerebral edema, lethargy, anorexia, seizures, etc.
  • diagnosis: plasma NH3 >150 with normal anion gap and normal glucose –> UCD
  • measure orotic acid for specific UCDs
  • can be def in CPS2, ASS, ASL, NAGS, OTC, or ARG
  • AR inheritance (OTC is X-linked)
  • treatment: dialysis and hemofiltration to dec Nh3, IV arginine hydrochloride and N scavenger drugs for alternative N excretion; restrict protein
  • if not treated –> cerebral edema, lethargy, anorexia, hyper/hypoventilation –> resp alkalosis, hypothermia, seizures, coma
  • initial signs: failure to feed, loss of thermoregulation, low temp, somnolence
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74
Q

CPS1 deficiency

A
  • most severe of UCDs

- hyperammonemia in newborn period

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75
Q

NAGS deficiency

A
  • N-acetylglutamate synthase def
  • similar to CPS1 def
  • NAG activates CPS1
76
Q

OTC deficiency

A
  • can be as severe as CPS1 def in males
  • 15% of female carriers get inc NH3
  • can have executive dysfcn
  • X-linked
  • most common
77
Q

ASS1 deficiency

A
  • citullinemia type1
  • ASS1 converts citrulline to argininosuccinate
  • inc NH3, but slightly easier to treat because can make some waste N
78
Q

ASL deficiency

A
  • argininosuccinic aciduria
  • inc NH3 in newborn
  • hepatic enlargement and inc AST and ALT
  • enlarged hepatocytes –> fibrosis
  • fragile hair, treat with arg supplemenet
79
Q

ARG deficiency

A
  • arginase deficiency
  • not usually inc NH3 rapidly
  • progressive spasticity, tremor, ataxia, choreoathetosis
  • affected growth
80
Q

Symptoms of lysosomal storage disorders

A

Brain:
- cognitive function, behavior, loss of skills

Skin:

  • thick, hirsutism, coarse
  • angiokeratoma in Fabry

Skull/brain:

  • *macrocephaly
  • *cognitive regression
  • seizures, ataxia, hydrocephalus, cognitive delay

Eyes:

  • *corneal clouding
  • *cherry red spot (Tay Sachs)
  • retinal degen

Hearing:
- loss due to otitis media

ENT:

  • *macroglossia
  • *sleep apnea
  • thick vocal cords, nasal congestion

Heart:
- cardiomyopathy, arrhythmia, thick valves

Lungs:
- fibrosis, airway narrowing

Liver:
- HSmegaly

GI:
- const and diarrhea

Kidneys:

  • *proteinuria in Fabry
  • renal failure

Skeletal:

  • *dysostosis multiplex (bony structure on xrays, vertebral beaking, broad bases for metacarpals)
  • *joint stiffness
  • *short stature
  • scoliosis

Muscle:
- hypotonia, myoclonic jerks, spasticity, weakness

81
Q

Gaucher Type 1

A
  • AR
  • def in beta glucosidase –> accumulate glucocerebroside
  • common in ashkenazi jews
  • bony pain (avascular necrosis)
  • hepatosplenomegaly
  • anemia
  • pancytopenia
  • restr lung dz
  • *Gaucher cells (crumpled tissue macrophages in bone marrow)
  • give beta glucosidase (glucocerebrosidase)
  • erlenmeyer flask femur on xray
82
Q

Tay Sachs Type 1

A
  • AR
  • def beta hexosaminosidase A –> build up of GM2 ganglioside
  • in infants
  • common in ashkenazi jews
  • blindness
  • seizures
  • mental and motor degen
  • fatal young
  • cherry red spot (but no HSmegaly)
  • supportive therapy
83
Q

Fabry

A
  • X-linked
  • child: acroparasthesia
  • adult: proteinuria, angiokeratomas
  • renal failure –> hypertrophy of heart
  • IBS
  • female have delayed disease
  • triad: peripheral neuropathy, angiokeratomas, hypohidrosis
  • def in alpha galactosidase A –> build up of ceramide trihexoside
  • treat with alpha galactosidase replacement, TIA and stroke ppx
84
Q

Niemann Pick A/B/C

A
  • AR
  • progressive neurodegen
  • HSmegaly
  • foam cells
  • cherry red spot
  • def in sphingomyelinase –> build up of sphingomyelin
85
Q

Pompe disease

A
  • AR
  • infant: muscle weakness (floppy) and hypertrophic cardiomyopathy
  • adult: proximal muscle weakness, normal heart, resp failure
  • def in alpha glucosidase –> alpha glucosidase replacement
86
Q

Hunter syndrome

A
  • X-linked
  • children: macroglossia, growth, airway, hearing loss, HSmegaly
  • coarse facies
  • NO corneal clouding
  • females don’t get it
  • def in iduronate sulfatase –> replace
87
Q

Hurler syndrome

A
  • AR
  • like Hunter but girls also affected
  • growth, coarse facies, airway, hearing loss, developmental delay, HSmegaly
  • corneal clouding
  • def in alpha-iduronidase –> replace
88
Q

McArdle disease

A
  • def in glycogen phosphorylase
  • muscle cramping
  • coffee urine after exercise (myoglobinuria
  • AR
89
Q

When do you feed a hospitalized patient?

A

4 factors:

1) patient’s pre-existing nutritional status
2) patient’s level of illness
3) consequences of inadequate nutrition
4) risks of feeding

  • if well nourished and minimal acute illness –> can go 10-14 days w/o food
  • if undernourished with minimal illness OR well nourished with severe illness –> 5-7days without food
  • if undernourished and serious illness –> can develop serious nutritional def in 3-5days if not fed
90
Q

Enteral vs. parenteral feeding

A
  • enteral: risk of aspiration
  • parenteral: risk of infection of IV line
  • preferred enteral
91
Q

What to feed patient?

A
  • most hospitals have standard liquid formula of fat, protein, carbs, vitamins, and trace elements from corn oil, maltodextrin, and casein
  • not so sick = 22-25kcal/kg/day
  • very sick = 30-32kcal/kg/day
  • formula is 1kcal/mL
  • start with low infusion rate and gradually increase
  • if can’t give enteral diet to meet needs, remember to give thiamine, folate, and multivitamin as you give them IV glucose (D5)
92
Q

Overfeeding vs. underfeeding

A

Overfeeding:

  • see hyperglycemia
  • takes 1-2days to resolved

Underfeeding:

  • negative protein balance
  • lose weight
  • protein req is usually 1g/day
93
Q

Respiratory failure diet

A
  • over feeding –> inc CO2 produced –> inc ventilation
  • avoid overfeeding
  • can give high fat diet (less CO2 per O2 consumed)
  • avoid underfeeding to allow nourishment of respiratory muscles
94
Q

Liver disease diet

A
  • hyperammonemia and ascites –> limit protein, salt, and water intake, but don’t underfeed
  • give diets lower in aromatic AAs and higher in BCAAs for false NTs dec
95
Q

Renal failure diet

A
  • inc BUN –> dec protein intake

- give more concentrated formula if volume overloaded

96
Q

CV disease diet

A
  • low saturated fat and cholesterol restriction
  • weight loss if obese
  • reduce salt intake if CHF
  • low fat, low Na, low sat fat, low cholesterol = cardiac diet
97
Q

Diabetes diet

A
  • use insulin to control blood sugar

- restrict carbs

98
Q

Name 3 applications of nutrition in medicine

A

1) public health and addressing chronic disease
2) ambulatory medicine: pregnancy, HTN, DM, etc.
3) nutrition support/inpatients: ICU, surgical, trauma, TPN, etc.

99
Q

Describe situations that place a patient at risk for nutritional problems

A

Nutritional depletion or excess signs:

  • impaired abs (CF, celiac disease)
  • dec utilization
  • inc loss (bleeding, diarrhea)
  • inc req: growth, pregnant, high metabolic rate, lactation, CV disease
  • high/low activity
  • nutrient/energy inadequacies

High risk patients:

  • very young or very old
  • underweight or recent loss of >10% body weight
  • obese with central fat/insulin resistance
  • limited variety in diet
  • long term nutrient loss: malabs, enteric fistulae, abscesses or wounds, renal dialysis, chronic bleeding or RBC destruction, bariatric surgery
  • hypermetabolic states: sepsis, fever, trauma, burns
  • chronic use of etoh or meds like steroids, IS, antitumor
  • socioeconomic factors
  • middle age with CV disease risk
  • post menopausal women
100
Q

ID and describe the components of nutrition assessment

A

1) history:
- intake of food and nutrients
- meds and supplements
- allergies to drugs and foods
- family history
- social history
- ROS

2) anthropometrics
- length, height, weight
- head circumference in babies
- waist circumference

3) exam:
- skin issues
- hair
- mouth
- extremities

4) labs;
- biochemical changes

101
Q

Describe 3 methods of obtaining diet info: questions to ask and content to be seeking

A

Qualitative

  • open ended qs
  • focused qs
  • listen for variety and restriction, excess, etc.

Semiquantitative:
- estimates within 24hrs

Quantitative
- record diet for one day

102
Q

Define nutrient req and allowance and the RDAs

A

Nutrient requirement: applies to groups, not individuals
Intake estimated to meet requirement defined by specified indicator of adequacy in 50% of the individuals in a life stage and gender group; includes an adjustment for assumed bioavailability of the nutrient; used to assess inadequate intakes and planning goal intake for mean intake of a group.
ex. Need one orange slice/day to keep scurvy at bay

Nutrient allowance - applies to individuals, not groups
RDA’s: average daily dietary intake level sufficient to meet the nutrient requirements of nearly all (95-97%) individuals in a life stage and gender group;
Guidelines have less emphasis of prevention of deficiency and more emphasis on decreased risk of chronic disease and health promotion

103
Q

Describe the aims of the US DG and how developed

A
  • promote health and reduce risk of chronic disease (CV, obesity, DM, cancer)
  • reissued every 5 years
104
Q

Describe key messages of the 2015-2020 DG and the rationale behind each

A

1) follow a health eating pattern across lifespan:
2) focus on variety, nutrient density, and amount
3) limit calories from added sugars and saturated fats, reduce Na intake
4) shift to healthier food and beverage choices
5) support healthy eating patterns for all

105
Q

Describe how current typical dietary patterns and food choices in US differ from DG

A
  • in US, we eat too much solid fats, added sugars, refined grains, and Na
  • also have excessive calorie intake
  • too few green veggies, orange vegetables, legumes, and whole grains, fruits, low fat dairy, and seafood
  • 20% eat less than 2300mg Na
106
Q

Describe how the USDA food guide (my plate) complements the messages in the DG

A
  • visual image

- simple messages

107
Q

Discuss 3 benefits of a diet rich in vegetables, fruits, whole grains, low fat dairy, health oils

A

source of vitamins and minerals

dec CV risk

happy bowels

108
Q

Water soluble vs. fat soluble

A

Water soluble:

  • non B-complex: vitamin C
  • B-complex –> energy metabolism, hematopoietic, other
  • Energy metabolism: thiamine, niacin, riboflavin, pantothenic acid
  • Hematopoietic: folic acid, B12
  • other: B6, choline, inositol, biotin
  • usually not stored except B12
  • get from diet
  • excrete through urine
  • low toxicity

Fat soluble:

  • ADEK
  • stored in body
  • requires dietary fat as a carrier
  • potential for toxicity because accumulate in fat
  • malabs with steatorrhea, CF
109
Q

Vitamin A

A
  • important in vision
  • maintains membranes and cornea
  • important for cell differentiation and proliferation of epithelial cells
  • get from liver, dairy, egg yolks, fish oil
  • precursor from spinach, carrots, broccoli, pumpkin

VitA deficiency:

  • night blindness and xerophthalmia –> blindness
  • immune def: give vitamin A supplement
  • flattened epithelial linings, dry and keratinized
  • treat measles with vitA
  • RFs: low intake, fat malabs, protein energy malnutrition

Toxicity:

  • only w/preformed, vomiting, inc ICP, HA, bone pain, bone mineral loss, liver damage, death
  • teratogenic

Evaluation:
- measure serum retinol; can remain normal until liver stores depleted and see dec with acute phase reaction

110
Q

Vitamin D

A
  • acts as a hormone
  • maintains IC and EC Ca
  • stim abs of Ca and P in intestine, reabs in kidney
  • inc bone mineralization at low levels
  • inc bone resorption at high levels
  • immune, cell growth, and differentiation
  • dehydrocholesterol in skin converted to cholecalciferol by UV light
  • diet: fish liver oils, fatty fish, egg yolks, fortified milk
  • abs by chylomicrons, hydroxylated in liver, then in kidney

Deficiency:

  • rickets: failure of maturation of cartilage and calcification
  • “rachitic rosary” on rib, bowed legs, widened metaphyses/wrists, painful bones, fractures
  • dec serum Ca and P, inc alk phos, inc PTH
  • RFs: lack of sunshine, low dietary intake, fat malabs, breastfeeding, dark skin, obesity, liver or kidney disease

Treatment:

  • supplement to all breastfed infants, 5-15min of unprotected sun exposure
  • hypervitaminosis: chronic granulomatous disease (sarcoidosis)

Toxicity:
- inc Ca, vomiting, seizures, nephrocalcinosis, soft tissue calcification

111
Q

Vitamin E

A
  • acts as an antioxidant and stabilizes cell membrane
  • from polyunsat vegetable oils, wheat germ
  • enhances warfarin

Deficiency:

  • neuro degen
  • loss of reflexes
  • ataxia, neuropathy, ophthalmoplegia, loss of coordination, vibration, position sense
  • hemolytic anemia
  • RFs: prematurity, fat malbs, CF
  • toxicity: low, coagulopathy –> can inhibit vit K dep factors
112
Q

Vitamin K

A
  • important for carboxylation of coagulation proteins (2, 7, 9, 10, C, S)
  • from leafy veggies, fruits, seeds, made from intestinal bacteria
  • warfarin is a vitK antagonist

Deficiency:

  • inc coag times
  • hemorrhagic disease of newborn (inc PT, inc PTT, normal bleeding time)
  • RFs: newborns, late breastfed infants, fat malabs, abx abuse
  • all newborns should get single IM dose
  • see rash/skin findings
113
Q

Risks for water soluble vitamin deficiency

A

1) dietary restrictions
- celiac
- allergies
- vegans

2) poverty
- poor diet

3) chronic disease
- esp if impacts absorption (bariatric surgery)

4) advanced age/high requirements (infants, kids, pregnant, lactation)

114
Q

Thiamine B1

A
  • TDP is a coenzyme for intermediary metabolism in cells, esp glycolysis, TCAC, AA metabolism, decarboxylation, transketolation
  • TTP binds Na channel in nerve membranes and plays a role in nerve conduction
  • source: whole grains, enriched grains, lean pork, legumes
  • RDA: 1.1-1.2
  • treatment: IM or IV thiamine

Deficiency:

  • dry beriberi: peripheral neuropathy, distal>proximal, muscle weakness
  • wet beriberi: edema and cardiac failure (tachy, cardiomegaly, CHF) + dry beriberi
  • wernicke-korsakoff: triad = ocular signs, ataxia, mental confusion; usualyl due to etoh abuse
  • evaluate with erythrocytes transketolase activity and blood thiamine levels
  • RFs: alcoholics, elderly, dialysis patients, high carb diet, refeeding after starvation, bariatric surgery
115
Q

Riboflavin B2

A
  • part of 2 coenzymes (FAD and FMN) that take part in red/ox reactions in TCAC and ox phos
  • AA and FA, vitamin K, folate, B6, and niacin metabolism
  • from liver, wheat germ, dairy, meats and poultry, leafy greens

Deficiency:

  • oral-ocular-genital syndrome –> cheilosis (cracked lips) and angular stomatitis (sores at corners of mouth)
  • inc vascularization of conjuctiva and photophobia
  • seborrheic dermatitis and scrotal dermatitis

Evaluation:
evaluate with erythrocyte GSH reductase activity coefficient (see inc in deficiency)
- RFs: women, infants, elderly, teens, in developing countries; subclinical in women taking OCPs

116
Q

Niacin B3

A
  • substituent of NAD and NADP
  • functions in glycolysis, TCAC, and ox phos and FAS and oxidation
  • from: meats, poultry, fish, peanut butter, legumes for preformed niacin
  • tryptophan is a precursor: find in milk, eggs
  • synth req B2 nd B6
  • treats dyslipidemia (dec VLDL and inc HDL)
  • RDA 14-16
  • treatment for deficiency: 50-100mg 3x/day for 3-4days

Deficiency:

  • pellagra: 4Ds
    1) dermatitis: symmetric, sun and heat aggravates; broad collar rash, hyperpig of sun exposed limbs
    2) dementia: confusion, dizziness, hallucinations
    3) diarrhea
    4) death

Toxicity:

  • causes vasodilation and flushing peripherally
  • can see inc serum uric acid, glucose intolerance, and liver damage

Evaluation:

  • urinary excretion of N1-methylnicotinamide and 2-pyridone (ration less than 1 = def)
  • serum niacin

RFs:

  • after months of poor intake
  • occurs where corn is major source of protein and calories
  • seen with malabs, alcoholism, cirrhosis
  • carincoid tumors can shunt tryptophan away from usual metabolic pathways
  • reactions with isoniazid
117
Q

Folate B9

A
  • converts to THF –> 1-carbon transfers for synth of nucleic acids and metabolism of AAs
  • converts homocysteine to methionine
  • plays a role in epigenetics as a methylator

Sources:
- deep green leaves, broccoli, orange juice, whole grains

RDA:

  • 400ug/day
  • women should take to prevent neural tube defects (600)

Deficiency:

  • macrocytic anemia
  • hypersegmented neutrophils
  • glossitis
  • inc plasma homocysteine
  • inc neural tube defects
  • no neuro symptoms

Evaluation:

  • RBC folate reflects tissue stores/chronic status
  • serum folate reflects recent intake
  • inc homocystein
  • normal methylmalonic acid
  • caused by phenytoin, sulfonamides, methotrxate

RFs:

  • pregnant women
  • infants/children if given goat’s milk
  • meds: dilantin, sulfasalazine
  • hemolytic anemia/blood loss
118
Q

Vitamin B12 (cobalamin)

A
  • 1-C transfers
  • folate metabolism
  • metabolism of odd chain FAs
  • reform THF from methylfolate (in formation of met)
  • methylmalonylCoA to succinylCoA (for lipid and CHO metabolism)
  • important for NA and protein synth
  • cofactor for met synth

Absorption:

  • cleave from dietary protein –> bind to IF from parietal cells –> B12-IF complex absorbed in distal ileum –> portal circ bound to transcobalamin2
  • liver stores 1-10mg
  • takes years to develop deficiency

Sources:
- only from animal products

RDA: 2.4ug/day

Deficiency:

  • macrocytic anemia
  • hypersegmented neutrophils + neuro problems (paresthesias, gait problems, depression; irreversible if long term)
  • do not treat with folate unless B12 def ruled out

Evaluation:

  • serum B12
  • urine/blood methylmalonic acid (inc in def)
  • serum homocysteine (inc in def)
  • inc MCV

RFs:
- poor ab: pernicious anemia, gastric atrophy, stomach or ileum resection, vegan diet, breastfed infant with def mom, AI conditions

119
Q

Pyridoxine B6

A
  • important in AA metabolism and interconversions for transamination
  • synth of cystathionine, heme, niacin, histamin, and NTs (serotonin, epi, NE, dopamine, and GABA)

Sources:
- animal products, vegetables, whole grains

RDA: 1.5mg/day

Deficiency:
- sideroblastic anemia, seizures, glossitis, depressiom

Evaluation:
- PLP, homcysteine

RFs:

  • use of isoniazid
  • ESRD
  • malabs
  • celiac, crohn’s UC
  • elderly
120
Q

Vitamin C

A
  • antioxidant/reducing agent
  • collagen synth
  • reduces Fe3+ to Fe2+
  • NE synth

Absorption:

  • dose dependent abs
  • if large intake, take divided less than 1g/dose during day

Sources:
- fruits, vegetables, broccoli, green pepper, citrus, potatoes

RDA: 80mg/d

Deficiency:

  • scurvy: def collagen formation in capillary BM; loss of catecholamine precursors
  • petechiae, bleeding gums, anemia, bruising, weakness, painful joints

Toxicity:

  • N/V/D
  • fatigue
  • inc risk of Fe toxicity

Evaluation:
- leukocyte or plasma vitamin c level

RFs:

  • lacking fruits and veggies
  • inc req for wound healing and burns
  • low income
  • smokers
121
Q

Rash/skin findings

A
  • niacin
  • vitamin c
    (- vitamin a)
  • vitamin k
122
Q

Mouth lesions

A
  • riboflavin
  • folate
  • b12
  • b6
  • vitC
123
Q

Neuro symptoms

A
  • thiamine
  • niacin
  • b12
  • b6
    (- vitC)
  • vitamin E
124
Q

Anemia

A
  • folate
  • b12
  • b6
  • vitamin C
  • vitamin E
    (- vitamin K)
125
Q

ID circumstances when risk of vitamin def or tox is high

A
  • all fat soluble
  • inadequate food intake
  • lack of variety
  • fat malabs
  • pancreatic insuff
  • liver disease –> low bile salts
  • protein energy malnutrition
  • inc nutrient req
  • inc metabolic demands
  • maldigestion
  • drug-untrient or medical treatment-nutrient interactions
126
Q

Iron

A

Function:

  • O2 transport in blood and muscle
  • electron transfer enzymes
  • oxidase and oxygenases

Sources:

  • cellular animal protein, meats, poultry, liver
  • legumes, nuts, whole grains, green veggies

RDA: 8mg/d (18 for female)

Absorption:

  • inc abs: heme from animal > non-heme; Fe def
  • dec abs: phytate, tannins; excess Zn or Cu; inflam
  • phylate and tannins affect formation of insolube complexes
  • vitamin C is important for reduced state of Fe
  • excess Zn or Cu dec Fe absorption
  • stress; Fe def –> inc absorption; inflammation –> inc hepcidin from liver –> dec absorption
  • abs inc with deficiency

Storage/transport:

  • transported by transferrin
  • stored as ferritin or hemosiderin

Deficiency:

  • usually due to bleeding
  • microcytic, hypochromic anemia
  • dec exercise/work tolerance, fatigue, listlessness
  • impaired cog fcn if deficiency w/o anemia

Toxicity:

  • Fe can be a pro oxidant
  • deposited as hemosiderin in reticuloendothelial cells
  • interfere with abs of Zn, Cu, and other minerals
  • hereditary hemochromatosis –> excessive Fe absorption due to defect in hepcidin –> damage to liver
  • see hemorrhagic gastroenteritis, shock and acidosis, coagulation defects, hepatic failure

RFs:
- infants, premies, pregnant women, chronic infestations, bariatric surgery, elderly

Diagnosis:

  • low Hb/Hct and microcytic/hypochromic rbs
  • low ferritin
  • low serum Fe and high TIBC

Treatment:

  • oral iron supplements 30-60mg/d for 2-6mo
  • 2-6mos to replenish stores
127
Q

Zinc

A
  • regulates gene expression
  • membrane stability
  • metalloenzymes
  • important in periods of growth and cell proliferation (immune system, wound healing, skin and GI tract integrity)
  • important esp in immune function

Sources:

  • animal products
  • beef > poultry > fish, milk, eggs
  • whole grains, legumes, etc.
  • abs is impaired by phytate
  • abs not increased with deficiency
  • inflam dec abs

RDA: 11mg/d

Homeostasis:

  • abs from diet and excretion from GI tract important for maintaining zinc pool
  • excreted as part of pancreatic biliary secretions; some reabs; some excreted

Deficiency:

  • mild: growth delays, anorexia, dec immune function, dec neuro development
  • moderate/severe: dermatitis (acro-orificial), diarrhea, immune dysfcn, delayed wound healing, taste impairment, anorexia, personality changes
  • acrodermatitis enteropathica: mutation in ZIP4 –> fatal if not treated; responds to high Zn supplements for life; severe dermatitis, growth failure, diarrhea
  • hypogonadism
  • dec adult hair
  • “diaper” dermatitis

RFs:

  • infants and young children (breastfed)
  • pregnant women
  • monotonous plant based diets
  • bariatric surgery
  • elderly
  • GI illness
  • wounds, burns
128
Q

Define malnutrition; describe its environmental and biological causes and clinical consequences

A
  • malnutrition is a multi nutritional deficiency complex where deficiency of energy is biggest deficit –> negative energy balance
  • seen in overcrowded and unsanitary living conditions
  • seen with maternal malnutrition and infectious disease
  • see impaired immune and GI fcn –> vicious cycle of malnutrition, infection and diarrhea
129
Q

Compare and contrast energy and substrate metabolism in short term and long term starvation

A

short term: gluconeo

long term: fatty acid ox –> ketone prod

130
Q

Marasmus

A
  • severe wasting of fat and muscle mass
  • due to energy deficiency
  • “simple starvation)
  • total calorie malnutrition –> emaciation
  • reduction in EE (dec activity, dec HR, dec temp)
  • dec Na pump activity
  • inc ketones and dec gluconeo
  • inc protein catabolism
  • dec inflam response and impaired immune function
  • loss of weight, muscle, fat
  • diarrhea
  • mild psych impairment
131
Q

Kwashiorkor

A
  • edematous PEM
  • without wasting
  • protein deficiency
  • related to metabolic stress and inflammation
  • skin lesions
  • liver malfunction
  • MEAL: malnutrition, edema, anemia, fatty liver
  • failure of normal adaptive response of protein sparing
  • due to infectious stress, cytokine release, relative micronutrient def, and free radicals
  • skin lesions (flaky paint)
  • hair and pigmentation changes (flag sign)
  • edema (moon facies)
  • hypoalbuminemia –> edema
  • inc insulin, dec lipolysis
  • inc hepatic FAS
  • edema, psych impairment, anorexia, infections, diarrhea
  • mild weight loss, muscle loss, fat loss
  • hepatomegaly and skin lesions
132
Q

How to manage severe PEM

A

1) resolve life threatening conditions
- restore circulation enterally
- K supplements; maybe Mg; avoid excess Na
- avoid hypoglycemia

2) restore nutritional status w/o disrupting homeostasis
- start slowly
- replete deficiencies

3) ensure nutritional rehab
- gradually advance intake
- look for resolution of edema
- supportive therapy

133
Q

Refeeding syndrome

A

Potassium:
- inc insulin secretion from feeding –> IC glucose and K –> dec serum K –> altered nerve and muscle function

Phosphorus:
- inc insulin –> intracellular P; inc intracellular phosphorylated intermediates; P trapped in IC space

Magnesium:
- inc req w/ inc metabolic rates

134
Q

PEM at different ages

A

0-12mos:

  • marasmus/severe wasting
  • most common PEM
  • stunting

12-24mos:
- kwashiorkor/edematous PEM

Older children:

  • stunting
  • degree of wasting milder

Pregnant/lactating women
- affects fetus, neonates, and infants

Elderly

135
Q

Describe framework for contextual factors that contribute to malnutrition

A
  • basic causes: lack of capital, socioeconomic and political factors
  • underlying causes: poverty, food insecurity, unhealthy household, environment, inadequate care
  • immediate causes: disease, inadequate care
136
Q

State and describe 3 major nutrition problems in developing countries, including growth, dietary, and reproductive outcomes

A
  • maternal and child under nutrition is underlying cause of 3.1mil deaths (45% of child deaths per year)
  • due to stunting, severe wasting, intrauterine growth restriction
  • maternal undernutrition
  • maternal overweight and obesity
  • undernutrition in pregnancy
  • vitamin A and Zn def –> death
137
Q

Describe the role of the impoverished gut and the triple burden of poverty: diarrhea, stunting, and chronic disease

A

a

138
Q

Describe 4 approaches to improving nutritional status in vulnerable populations

A
  • scale up 10+ interventions to 90% coverage –> 15% reduction i ndeaths in less than 5yo children:
    1) folic acid before pregnancy
    2) maternal balanced protein energy supplement
    3) maternal Ca supp
    4) multiple micronutrient supp in pregnancy
    5) promote breastfeeding
    6) appropriate complementary feeding
    7) vit A supp
    8) preventative Zn supp
    9) manage severe acute malnutrition
    10) manage moderate acute malnutrition
139
Q

Define obesity using BMI and waist circumference

A
  • wt/height^2
  • normal = 18.5-25
  • OW = 25-29.9
  • obese stage 1 = 30-35
  • obese stage 2= 35-40
  • obese stage 3 = >40
  • men waist >40
  • women waist >35
  • indicates high medical risk
  • WC shows location of adiposity
  • abd fat has greater risk than fat in other areas; assoc w visceral fat
  • indep RF for T2DM, CV disease, HTN, hypercholesterolemia, and mortality
140
Q

List the possible causes of obesity

A
  • calories in > calories out
  • dec physical activity
  • food is better tasting and larger portions
  • ## genetic and environmental
141
Q

Define metabolic syndrome using the current AHA/NCEP definition

A
  • specific body phenotype of abd obesity assoc with metabolic disorders that are RFs for CV disease
  • abd obesity, HTN, inc TGs, low HDL, T2DM
  • definition is 3+ of:
    1) abd obesity (>40in male, >35in female)
    2) TGs >150
    3) HDL less than 40 (male), 50 (female)
    4) BP >130/85
    5) fasting glucose >100
142
Q

List the steps in the clinical evaluation of the obese patient

A

1) measure degree of adiposity
2) assess other RFs for CV disease
3) screen for complications
4) rule out medical causes
5) assess readiness for treatment

History:

  • history of weight changes
  • previous weight loss attempts
  • meds
  • smoking history
  • family history
  • current diet
  • readiness

Exam:

  • BMI
  • waist
  • BP
  • HR and O2sat
  • signs of pulmHTN (edema, skin hyperpig)
  • thyroid disease
  • diabetes

Labs:

  • TSH
  • fasting glucose of HbA1c
  • lipid panel
  • liver enzymes
143
Q

What are the 3 groups where BMI can over or underestimate health risk?

A

1) muscular people: can overestimate
2) elderly: can underestimate
3) abdominal obesity: can underestimate

144
Q

Overweight BMI

A
  • 25-29.9 kg/m^2
145
Q

Obese BMI

A
  • 30-34.9kg/m^2
146
Q

Severe (stage 3) obesity BMI

A
  • > 40kg/m^2
    or
  • > 35kg/m^2 with a weight related medical complication like diabetes
147
Q

What are comorbidities with obesity?

A
  • sleep apnea
  • T2DM*
  • HTN*
  • hyperlipidemia*
  • CV disease*
  • fatty liver disease*
  • erectile dysfunction
  • PCOS
  • infertility
  • cancer
  • depression
  • low back pain
  • OA
148
Q

T2DM and obesity

A
  • BMI, abd fat, and weight gan are RFs for T2DM
  • 70% of people with T2DM have BMI >27
  • risk of diabetes is directly proportional to BMI
  • women with BMI 23-24 have 3.6x higher risk of diabetes than women with BMI less than 22
149
Q

Recognize the appropriate application of diet, physical activity, and behavioral changes in obesity treatment

A
  • calorie rest diets
  • keep balanced diet in long term
  • physical activity to improve appetite regulation, maintain weight loss, inc overall health, preserve fat free mass, dec CV risk
  • physical activity + diet
150
Q

Recognize that weight bias exists and is prevalent among physicians

A

yep

- use the word “weight”

151
Q

List specific dietary approaches that can be used in the office to help obese patients achieve a negative energy balance and lose weight

A
  • self-monitor
  • lower energy density food/smaller portion sizes
  • cut out sugary drinks
  • inc fruits and veggies
  • slow pace of eating
  • follow a diet
  • meal replacement
  • weight loss program
152
Q

Define the amount of physical activity that is recommended to maintain general health, to prevent weight gain, and to prevent weight regain in individuals that were previously obese

A

150min/week of moderate
75min/week of vigorous

for long term:

  • 60min/day of moderate
  • 30min/day of vigorous
153
Q

Describe the use of pedometers and the evidence for counseling patients about both programmed physical activity as well as lifestyle physical activity

A
  • get basedline/day of steps
  • set goal to inc # of steps/day by 500 (5min of walking)
  • aim to 10k steps a day
154
Q

List the behaviors that individuals in the National Weight Control Registry report to help them maintain a reduced weight

A

1) use of moderately low fat, high carb diets (24% fat, 19% protein, 55% carb)
2) frequent self monitoring
3) eating breakfast
4) lots of physical activity
5) limit tv watching

155
Q

Describe the respective roles of the hypothalamus, specifically the arcuate nucleus, paraventricular nucleus, ventromedial nucleus, and lateral hypothalamus in the regulation of energy balance and body weight regulation

A
  • hypothalamus involved in short and long term reg of body weight
  • (-) VMN: satiety center
  • (+) LH: causes voracious eating
  • (+-) AN: NPY/AgRP –> hunger; POMC/CART –> satiety
  • (+-PVN): NPY activates NPYRs –> stim eating; MCR binding –> stim satiety
156
Q

Describe the mechanisms used by the hypothalamus to promote and inhibit food intake, and predict the impact on food intake and body weight of: POMC knockout, NPY knockout, MCR loss of function

A
  • regulate food intake
  • alter gastric motility
  • alter food metabolism/utilization
  • LH supports chewing, licking, swallowing

1) POMC knockout (and therefor alphaMSH) –> inc weight
2) NPY knockout –> dec weight
3) MCR loss of function –> inc weight

157
Q

Discuss the role of brain reward pathways and environmental cues in the development of obesity

A

Internal inputs:

  • reward
  • cravings
  • thinking about food
  • restraint
  • learned behaviors
  • attention

External inputs

  • environment
  • availability
  • social context
  • time cues
158
Q

ventromedial nucleus and hypothalamus in short term eating regulation

A
  • determine meal size and frequency
  • hypothalamus is hunger center
  • ventromedial nucleus (VMN) is satiety center
  • lateral hypothalamus stim –> voracious eating (lesions = no eating)
  • LH neurons produce MCH and orexins –> induce feeding; innervate brainstem, medulla, and spinal cord
  • VMN stim –> cessation of eating (lesion = excessive eating)
  • ## VMN lesions reset regulated weight to higher level
159
Q

arcuate nucleus and paraventricular nucleus in short term eating regulation

A
  • two neuron populations
    1) arcuate nucleus has 1st order neurons that produce neuropeptide Y (NPY) and AgRP –> promote feeding: blocks effect of alphaMSH on MCR and activates NPYRs –> anabolic pathway act (inc food intake, dec EE)

2) act of arcuate neurons POMC/CART that produce alphaMSH and CART –> promote satiety: activate MCR –> catabolic pathway (dec food intake, inc EE)
- innervate symp pregang in spinal cord
- alphaMSH is a product of POMC

both:
- these neurons target hypothalamus, including PVN and LH

160
Q

GI signals regulating body’s need for food and terminating intake

A

Ghrelin:

  • secreted from stomach
  • induces feeding
  • peak prior to a meal
  • receptors located in AN
  • activates NPY/AgRP pathway and inh POMC/CART pathway

Gastric distention:
- info about distention + hepatic glucose and lipids –> nucleus of tractus solitarius through vagal afferents –> PVN + AN + LH + amygdala + visceral sensory thalamus –> visceral sensory cortex

CCK
- duodenum signals presence of nutrients to brain by releasing CCK –> act vagal afferents in peritoneum and brainstem pathways to hypothalamus

Peptide release:

  • GLP-1: synth in L cells of distal ileum due to nutrients; act pathways leading to dec food intake
  • peptide YY: released from L cells of distal ileum due to nutrients; anorexic effects by inh NPY/AgPR neurons

Glucose:

  • hypoglycemia –> stim eating
  • hyperglycemia –> inh eating
  • glucose sensitive neurons in VMN and LH (also AN and NTS)
  • VMN stim by hyperglycemia (lesions = obesity)
  • LH inh by glucose
161
Q

Long term regulation of food intake

A
  • controlled by fat/adipose levels –> send a circulating factor that suppresses appetite, leptin

Leptin:

  • the satiety hormone
  • site of action is brain
  • results in dec appetite and weight loss
  • receptor is in AN and VMN
  • inhibits PY/AgRP pathway
  • act POMC/CART
  • act satiety, inh feeding

Insulin:

  • circulates at levels that parallel body fat mass
  • similar effects as leptin (activates satiety/catabolic pathways, inh feeding/anabolic pathways)
162
Q

State the definitions and classification of childhood weight status, including use of BMI for age charts

A
  • overweight: BMIoas between 85% an 94%; 50% have excess adiposity and need to watch out
  • obese: BMI>95%
  • severe obesity: BMI>99%
  • use a chart
163
Q

Describe the current demographics of childhood overweight and obesity, including national rates, ethnic, and age distributions

A
  • 2-19yo: 18% of children are obese
  • 30% are either obese or overweight
  • higher in american indian, african american, latino pops
  • inc with age but not sex
164
Q

Introduce major comorbidities assoc w childhood obesity

A

Most common: OSA, metabolic syndrome, NASH, dec QOL, mood and anxiety problems

Pulm:

  • sleep apnea
  • pulm HTN –> right sided HF

CV:

  • atherosclerosis
  • dyslipidemia
  • HTN
  • coagulopathy
  • chronic inflam
  • endothelial dysfcn

Endocrine

  • T2DM
  • PCOS
  • hypothyroid

GI:

  • NASH
  • GERD
  • gallstones
  • constipation

Neuro/eye problems:
- pseudotumor cerebri: papilledema, peripheral vision loss, HA

Orthopedic:

  • femoral head misalignment
  • blounts disease

Psych:

  • depression
  • anxiety
  • eating disorder
165
Q

Describe key components of assessment including diet physical activity, family history, ROS, phys exam, and labs

A

1) plot BMI at least yearly when 2+ yo
2) assess targeted diet and activity history and family history of CV RFs
3) ROS for comorbidities
4) labs: fasting glucose, lipids, ALT, A1c

  • family history of obesity and CV RFs
  • motivational interviewing
166
Q

Briefly describe essential treatment principles

A
  • diet: fruits and veggies, low fat dairy
  • no sweetened drinks or fast food
  • 5210; 5 fruits/veggies, less than 2hrs screen time, >1hr activity, 0 sugary drinks
167
Q

List the common meds that are used for other health problems that contribute to weight gain and describe an approach to minimizing this problem

A
  • birth control pills
  • sulfonylureas, insulin TZDs
  • mood stabilizers + antipsychotics
  • prednisone
  • monitor weight
  • choose alternative
  • lower dose
  • weigh pros and cons

alternatives:

  • ziprasidone and aripiprazole for antipsychotics
  • buproprion for antidepressants
  • GLP1 agonists, DPP4 antagonists, and SGLT2 inh for diabetes
168
Q

Phentermine

A
  • inc brain NE levels
  • generic and inexpensive $30/month
  • usually 5% of baseline weight loss
  • inc satiety and dec food intake
  • side effects: nervousness, insomnia, HA, dry mouth, inc in BP
  • don’t give to people with HTN
  • only FDA approved for 3mos of use
169
Q

Orlistat

A
  • pancreatic lipase inhibitor –> blocks dietary fat abs from GI tract
  • cost 100$/mo
  • 5% weight loss
  • no systemic side effects
  • side effects: steatorrhea
  • interacts with coumadin (inc INR) and cyclosporine (dec drug levels)
  • can be used for long term
  • can prevent development of diabetes in high risk patients, improves lipids and dec A1c
170
Q

Lorcasarin

A
  • selective serotonin 2C receptor agonist
  • only found in brain
  • 4-5% weight loss
  • no CV problems
  • $100/mo
  • approved for long term use
171
Q

Phentermine/topiramate

A
  • may have teratogenic potential
  • $150/mo
  • 8-10% weight loss
  • side effects: dry mouth, paresthesias, insomnia, dizziness, anxiety, irritability, and attention problems
172
Q

Naltrexone SR/Buproprion SR (contrave)

A
  • 5% weight lss
  • black box warning of inc risk of suicidal ideation
  • gradually inc dose over a moth
  • side effects: suicidal ideation, lowering seizure threshold, inc BP and HR, sometimes inc LFTs, closed angle glaucoma
  • $150/mo
173
Q

Liraglutide (saxenda)

A
  • GLP1 agonist
  • 5-7% weight loss
  • side effects: nausea, sometimes pancreatitis
  • $1000/mo
174
Q

Weight loss surgery

A
  • lap band, sleeve gastrectomy, RYGB, biliary pancreatic diversion
  • lap bad does not have long term success

RYGB:

  • helps a lot in glucose control in DM
  • 30% weight loss; most effective but most risky
  • food goes directly into intestine –> inc satiety; dec ghrelin –> dec hunger
  • risk of dying, TE, leak, infection; niacin, B12, vitD, Fe def

Lap band:

  • 25% weight loss
  • least weight loss, least risk
  • dec size of stomach, inc satiety
  • mech failure

Sleeve gastrectomy

  • glucose control in DM
  • 27% weight loss
  • inc satiety
175
Q

Risks and benefits of weight loss surgery

A
  • .7% risk of death with 0-2% within 30 days of RYGB
  • PE, infections, mech problems
  • be on vitamins
  • can see thiamine deficiency
  • also vitamin D, Fe, and B12 def
  • benefits: resolution of T2DM with RYGB 40%
176
Q

Who is appropriate for drugs or surgery?

A
  • meds: BMI>30 without comorbidities or >27 with

- surgery: BMI>40 without comorbidities or >35 with

177
Q

List the key elements of effective behavior change counseling

A
  • needs to come for patient
  • must see need for change
  • patient needs to feel confident
  • be empathetic
178
Q

List the stages of change and typical responses that a patient might make in a clinical interview that help you establish their stage

A
  • precontemplative: don’t see/accept need to change
  • contemplative: see need to change, no confidence
  • planning: see need, has confidence; try to inc courage
  • action: IDd need and made change, help with future challenges
  • maintenance: relapse or retain
  • relapse: talk about past and moving forward
  • ID: pt change and has long term success
179
Q

Describe the primary goal of motivational interviewing and list the key principles of this counseling styl

A
  • people feel ambivalent about proposed change
  • have pt clearly articulate and work towards resolving ambivalence
  • quiet and eliciting opinion
  • focus on ambivalence
  • readiness to change
  • partnership
  • pt self efficacy
180
Q

Describe 2 important steps in values based counseling

A
  • explore with patients what their core values are

- tie health related behaviors to these core values

181
Q

List the key criteria address in the health belief model

A
  • most pts don’t believe what we tell them
  • change and adherence occur when: understand risk, risk is serious, treatment is effective, has a reason to take action, confident to take actions
182
Q

ID situations where CBT might be the best counseling model to use

A
  • undesired behaviors are a result of unconscious or unhelpful ideas
  • their behaviors are inexplicable
  • have patient work backwards in time
  • come up with specific strategies to counteract behavior
183
Q

Pure inc TG

A
  • LPL deficiency

- C2 deficiency

184
Q

Pure inc LDL

A

Familial hypercholesterolemia

185
Q

Both inc TG and inc LDL

A

Familial combined or DBL

186
Q

Low HDL only

A

Tangiers

187
Q

High HDL

A

CETP

DEMS (4 decks)

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