Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MHG - Exam 2 > Lecture 25-Biochemical Metabolism > Flashcards

Lecture 25-Biochemical Metabolism Flashcards

1
Q

Metabolic disease or IEMs represent one of the few diseases where prompt recognitino can ________

A
  • significantly improve outcome and morbidity/mortality, particularly in intermediary metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

Sir Archibold Garrod

A
  • characterized alkaptonuria in that it has familiar distribution, especially in consanguineous marriages
  • found that lifelong diseases can arise due to an enzyme governing a single metabolic step that reduce activity or get rid of it altogether
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

IEMs predominately have what type of inheritance?

A
  • autosomal recessive aside from the X-linked ones (like OTC)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Genetic changes can result in ____, _____, _____ or ______ defects.

A
  • complete
  • partial
  • enhanced
  • conditional
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the different ways that genetic changes can impact metabolism? (2)

A
  • when it affects a protein that is part of a complex so it’s effect reaches beyond just that one enzyme (i.e., the enzyme itself being defective isnt as big of a deal as the fact that it disrupts the complex)
  • some changes affect kinetics and wont show up until stress is applied (like chemo)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is an example of the idea that the line between polymorphisms and mutations are not clear cut? That shows the environments role in promoting mutations…

A
  • Hemachromatosis: Inborn error that affects iron metabolism. What once was advantageous now causes Fe levels in our american diet to lead to Fe accumulation to toxic levels in people of Irish descent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why are newborns most vulnerable to IEMs?

A
  • just came off of 9 mos of life support
  • placenta and mom removed most of the harmful substances for the fetus
  • newborn state highly catabolic!!!
  • all sources of energy are used (carbs, fats, proteins) since energy use exceeds production in first few days
  • most biochemical enzymes not at mature levels (ex: urea cycle at ~40% or <
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

GENERALLY speaking, how do these patients present?

A
  • increased incidence of neurodevelopmental and behavioral problems (because the brain uses the most energy–25% while growing, 15% as adults)
  • global delay
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why do patients with IEMs generally present with neurodevelopmental and behavioral problems?

A
  • brain uses most of our energy
  • these IEMs cause general neurotoxicity (although some can be highly specific-ex: gly)
  • brain uses many intermediates of metabolism as NTs
  • it is often the first place hit when things go awry
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the top suspects in IEMs? (5)

A
  • glycine
  • ammonia
  • lactate
  • galactose
  • organic acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why is glycine toxic?

A
  • a commonly produced aa but also a NT so high levels disrupt normal neuronal firing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is ammonia toxic?

A
  • affects aa transport

- ammonia has an inhibitory affect on AQPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is lactate toxic?

A
  • irritant to muscle even though it’s a good energy source to neurons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why is galactose toxic?

A
  • galactose is NOT toxic, but it’s converted into galacterol which is a neurotoxin that can build in the liver and lens of the eye to cause damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why are organic acids toxic?

A
  • these biochemical intermediates should never be seen in the blood! They are immediately converted to their products so if they’re there something is wrong. Also, these help point to where the issue is.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe when these problems usually manifest and why.

A
  • normal at birth, stable
  • metabolite needs time to build up or drop down (can be 24 hr to 1-2 weeks as the system is stressed)
  • Kids are coming in with more toxic conditions because kids dont stay in the hospital as long as they use to an when they get home parents just think that they’re tired (highly catabolic state!!)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

IEMs generally look like what condition? Why is this dangerous?

A
  • sepsis

- Because doctors will try to treat the sepsis and not look for underlying metabolic disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do these diseases normally affect the brain? (5)

A
  • toxin destruction of neurons
  • toxin disruption of neuron function
  • over/under accumulation of metabolite that is also a NT
  • not enough fuel
  • unknown origin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are 2 agents that can build up in IEMs that destroy neurons?

A
  • phenylalanine

- phenylacetic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What agent can disrupt function of neurons?

A
  • ammonia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the symptoms as the brain is increasingly affected by build up of toxins? (6 initial)

A
  • anorexia
  • sleepiness
  • vomiting
  • temperature instability
  • hiccups
  • hypotonia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the symptoms as the brain is increasingly affected by build up of toxins? (9-advanced)

A
  • lethargy
  • coma
  • seizures
  • respiratory arrest
  • immune impairment
  • hepatic dysfunction
  • decorticate posturing
  • cardiomyopathy
  • death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What happens when ammonia inhibits aquaporins in the brain?

A
  • brain swells because cells aren’t releasing water
  • puts pressure on the brainstem which slows blood flow as it pumps against the swollen brain
  • decreased HR makes the brain think that the body is acidotic so it increases the respiratory rate actually making the body alkalotic (7.6-7.7)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the 3 NTs that could build up during a IEM and cause problems? Stimulatory or inhibitory?

A
  • gly
  • glu
  • gln
  • both stimulatory and inhibitory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why can the lack of fuel caused by the IEM be a problem?

A
  • the brain is already on the border of biochemical sufficiency so if glycolysis or the TCA are disrupted this causes lactic acid buildup and other alternative pathways become toxic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Give an example of a substance that for unknown reasons causes brain toxicity and how.

A
  • homocysteinuria

- can cause schizophrenia in previously normal people

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When people develop cerebral edema, once it starts to resolve it looks like _____.

A

a stroke

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the common labs you should use to diagnose an IEM? (7)

A
  • CBC
  • Urinalysis
  • blood gas
  • electrolytes
  • blood glu
  • blood ammonia and BUN
  • lactate and pyruvate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why use CBC?

A
  • detects pancytopenia (deficiency of all 3 cellular components: RBCs, WBCs, platelets)
    from organic acids causing bone marrow suppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Why use urinalysis?

A
  • detects ketone bodies: indicative of function of FA oxidation
  • reducing substances (galactose and fructose)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Why use blood gas test?

A
  • detects acidosis (metabolic)/alkalosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why use Electrolyte test?

A
  • detects anion gap: Na minus Cl minus CO2 which should normally be less than 15.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Why test blood glucose?

A
  • detects defects in gluconeogenesis and energy substrate production (FA, etc.)–makes sure pathways are intact
  • detects issues with substrate storage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Why test blood ammonia and BUN?

A
  • detects 1º and 2º defects in urea cycle

- important for looking at N levels

26
Q

Why test lactate and pyruvate levels? (5)

A
  • detect defects in pyruvate metabolism
  • and energy production/use
  • and ETC
  • detects inefficient metabolism
  • detects stress
27
Q

What are the 3 of the main specialty labs we should use to finalize our diagnosis? (3)

A
  • Plasma AAs (PAAs)
  • urine OAs (UOAs)
  • ACP: acyl carnitine profiles
28
Q

Why test for PAAs?

A
  • detects breaks in normal AA metabolism or secondary affects on AA metabolism
29
Q

Where do OAs come from?

A
  • metabolites of protein and FA metabolism
30
Q

Why test for UOAs?

A
  • detects primary and secondary metabolites of unprocessed organic acids
31
Q

Why test for ACP?

A
  • detects organic acids in blood bound to carnitine

- detects unprocessed FA intermediates

32
Q

What does carnitine do besides shuttle FAs into the mitochondria?

A
  • solubilizes hydrophobic things and can carry them in the blood
33
Q

PAAs (tested using HPLC) are best for testing for what enzyme deficiencies (3)? What disease and why?

A
  • ASS
  • ASA
  • arginase
  • MSUD: detects alloisoleucine as well as high Ile, Leu, Val
34
Q

What are some of the main diagnoses you can make from UOAs? (4)

A
  • MMA/PA
  • IVA
  • MSUD
  • MCAD
35
Q

In a UOA analysis using GC/MS, what would be diagnostic of MMA/PA?

A
  • methylcitric acid

- 3OH-propionate

36
Q

In a UOA analysis, what would be diagnostic of IVA?

A
  • isovalerylglycine
37
Q

In a UOA analysis, what would be diagnostic of MSUD?

A
  • abnormal ketoacids
38
Q

In a UOA analysis, what would be diagnostic of MCAD?

A
  • Hexanoylglycine and others
39
Q

ACP analysis using LC/MS/MS is best for detecting _____. What is it’s caveat?

A
  • organic acidemias

- may not be able to distinguish disease without UOAs

40
Q

What are other diseases that may look like metabolic disease? (8)

A
  • heart disease
  • seizures
  • code
  • starvation
  • liver disease
  • valproate and other drugs
  • TPN
  • Penicillins
41
Q

What diseases look like IEM because they cause lactic acidosis? (4)

A
  • heart disease
  • code
  • seizures
  • starvation
42
Q

Why does starvation look like IEM? (3)

A
  • ketosis
  • varying aa levels
  • lactic acidosis
43
Q

Why do people on valproate and other drugs look like they may have an IEM? (2)

A
  • elevated ammonia

- elevated gly

44
Q

why may people on TPN look like they have an IEM?

A
  • if IV is not cleaned before taking a blood sample it can show high aas
45
Q

Why may people on antibiotics look like they have an IEM?

A
  • false positive for reducing substances when normally they’d be looking for galactose and fructose. People who are in the hospital are probably on antibiotics already because these IEMs look like SEPSIS!!
46
Q

Why do people with liver disease look like they may have an IEM?

A
  • hypoglycemia

- AA elevations (Phe, Tyr, branched, Met, Homocysteine)

47
Q

What are the main functions of the urea cycle?

A
  • converts N (ammonia and aspartate) to urea
  • generates arginine (and therefore NO)
  • replenishes intermediates
48
Q

Where is the urea cycle?

A
  • in the liver
  • proximal cycle (NAGS, CPS, OTC) in gut
  • distal cycle (ASS, ASL, ARG) in kidney
49
Q

Any block on the urea cycle makes ____ an essential aa.

A

arginine

50
Q

if there is a block in the urea cycle, how does the level of ammonia change in our bodies?

A
  • usually 30µM, but will rise to 2-3 mM in 24 hrs
51
Q

How do urea cycle patients usually present?

A
  • in newborn period (<7 days) with:
  • hyperammonemia: acutely life-threatening if HA is not recognized and reversed
  • vomiting (from increased ammonia)
  • lethargy (remember: these kids are in highly catabolic state!!)
  • respiratory ALKALOSIS with hyperventilation. pH normal to alkalotic
52
Q

Patients with urea cycle defects are often mistaken for having _____. This is why it’s important to check _______.

A
  • overwhelming infection

- N levels

53
Q

When will a urea cycle defect patient be acidotic?

A
  • when there are in SEVERE respiratory depression
54
Q

What are the steps to diagnosing someone with a UCD after you have found hyperammonemia? (2)

A
  • check PAAs, ACP, UOAs

- check for sepsis, especially herpes

55
Q

hyperammonemia is also seen in ______.

A

organic acidemias: proprionic acid interferes with NAGS

56
Q

How would PAAs, ACP, and UOAs be if the patient has a UCD?

A
  • ACP, UOAs are normal

- Characteristic changes in PAAs (note: PAA can detect changes in all urea cycle intermediates)

57
Q

What is the most common urea cycle disruption? Inheritance?

A
  • OTC

- X-linked

58
Q

what are ways to reduce the amount of ammonia produced? (3)

A
  • reduce input of protein
  • dialysis
  • ammonia trapping/scavenging
  • reduce protein breakdown
59
Q

When is reducing protein input a problem?

A
  • in babies when they need the protein because they’re growing
  • also, because we can’t make all the protein that we need our body will provoke the catabolic state to breakdown aas from other places in the body
60
Q

What agents are ammonia trapping and what do they trap?

A
  • sodium benzoate: glycine

- phenylacetate: glutamine

61
Q

UCD patients will also have high blood ______. Why? What are the implications of this?

A
  • Glutamine
  • its acting as a final N acceptor
  • causes lowering of Glu and because Gln is a NT in the brain the low Glu and high Gln can disrupt the brain
62
Q

What are ways to reduce protein breakdown in patients with UCD?

A
  • give excess calories

- can temporarily give insulin to induce an anabolic state

63
Q

hyperammonemia is also seen in ______

A

organic acidemias

64
Q

How would PAAs, ACP, and UOAs be if the patient has a UCD?

A
  • ACP, UOAs are normal

- Characteristic changes in PAAs

65
Q

What is the most common urea cycle disruption? Inheritance?

A
  • OTC

- X-linked

66
Q

what are ways to reduce the amount of ammonia produced? (3)

A
  • reduce input of protein
  • dialysis
  • ammonia trapping/scavenging
  • reduce protein breakdown
67
Q

When is reducing protein input a problem?

A
  • in babies when they need the protein because they’re growing
  • also, because we can’t make all the protein that we need our body will provoke the catabolic state to breakdown aas from other places in the body
68
Q

What agents are ammonia trapping and what do they trap?

A
  • sodium benzoate: glycine

- phenylacetate: glutamine

69
Q

UCD patients will also have high blood ______. Why? What are the implications of this?

A
  • Glutamine
  • its acting as a final N acceptor
  • causes lowering of Glu and because Gln is a NT in the brain the low Glu and high Gln can disrupt the brain
70
Q

What are ways to reduce protein breakdown in patients with UCD?

A
  • give excess calories

- can temporarily give insulin to induce an anabolic state

71
Q

Why are N scavenging agents helpful?

A
  • they help alleviate the ammonia load but also can be excreted by the kidneys and pull loose N in
72
Q

What is a common treatment for UCDs?

A
  • liver transplant
73
Q

In conclusion with UCDs what are the things that disrupt the urea cycle? (5)

A
  • genetic enzyme defect
  • damage to the liver: chemical toxins/infections
  • drugs
  • overloading the system: hemolysis and protein catabolism
  • others: bariatric surgery, atkins diet
74
Q

Note:

A

stopped on slide 34, page 12 of alana’s notes

MHG - Exam 2 (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions