Lecture 25+26 Flashcards
PKU generally
common (but rare)
autosomal recessive disorder
determined by mass spec.
responds well to treatment of low Phe diet
low protein, no eggs/milk/meat
no aspartate
can live normal life if following diet
biochemical defect in PKU
no phenylalanine hydrolase enzyme
thus more phenylalanine and less tyrosine
build up of phenylpyruvic acid
need tyrosine in diet
signs of PKU
delay milestones
low IQ
mousy odor of urine (due to Phe metabolite build up)
Phe levels are high in blood
decreased pigmentation of skin and hair
tyrosine conversion to melanin is inhibited by high phe levels; inhibits tyrosinase
Treatment for those with PKU
dietary treatment- avoid phenylalanine
sapropterin (synthetic form of BH4)
typically for mild or moderate forms of disease
mutant from of enzyme that has low affinity for BH4
first non-diet treatment considered
maternal PKU syndrome
women with PKU must maintain low levels of Phe before conception and pregnancy
high maternal blood levels of Phe:
microcephaly
lack of mental development
congenital heart defects
elevated Phe has teratogenic properties!!
does not matter if fetus has PKU or not
alkaptonuria
homogentisic acid oxidase deficiency
build up of homogentisic acid
dietary restriction of Phe and tyrosine may reduce the deposits of homogentisic acid
alkaptonuria signs
darkening of the urine on standing
discoloration of the cartilage and connective tissues
(ochronotic pigment)
leads to arthritis
these symptoms are due to the oxidation of homogentisic acid
tyrosinemia type I
build up of fumaryl acetoacetate
leads to kidney and liver damage
cabbage-like smell of the urine
tyrosinosis or tyrosinemia type I
inborn error of phenylalanine tyrosine metabolism
seen to have a fumarylacetoacetate hydrolase deficiency
liver and kidney failure
cabbage smell to urine
dietary restriction of phe and tyr
difficult to accomplish
maple syrup urine disease (MSUD)
symptoms occur in neonates aged 4-7 days
can be detected by neonatal screening
signs/symptoms: poor feeding vomiting lethargy seizures ketosis (sweet smell of urine) coma / death if not treated
biochemical defect in MSUD
cannot break down branched chain amino acids
No Branched chain α-keto acid dehydrogenase
thus build of of branched amino acids
treatment for MSUD
No intake of leucine, isoleucine, or valine
improves neurological functions
difficult to treat
BCAA found in most protein sources and are essential
dietary supplementation of B1 in those that have a low affinity enzyme
regular checking of BCAA in blood
Methylmalonyl CoA mutase deficiency
results increased levels of methylmalonic acid in circulation
will lead to metabolic acidosis
can have seizures and encephalopathy
sometimes have improvement with B12 supplementation
homocystinuria
defect in the metabolism of homocysteine
high plasma and urinary levels of homocysteine
due to a deficiency in cystathionine Beta synthase (transulfuration pathway)
homocystinuria signs/symptoms
homocysteine can bind to connective tissues and disrupt structure
dislocation of lens (after age 3) skeletal abnormalities osteoporosis delay in mental development premature arterial disease (lipid deposits) (lipid oxidation and platelet aggregation)
may respond to vit B6 supplement
general composition of pancreatic secretions
same Na and K as plasma - isotonic
high HCO3 concentration (alkaline)
Low Cl-
enzymes:
lipase, amylase, proteases
rate:
low flow: mostly Na and Cl
high flow: mostly Na and HCO3
both isotonic
secretin secretion
secreted from S cells from duodenum
in response to H+ in lumen
leads to increased HCO3
CCK secretion
secreted from the I cells in the duodenum
in response to small peptides, AA’s, and fatty acids
effect:
increased enzyme secretion
increased HCO3 secretion
ACh secretion
secreted from vagus terminals
in response: H+, small peptides, AA’s, FA’s
effect:
increased enzyme secretion and increased HCO3 secretion
pancreatic acinar cells
low volume, NaCl, and enzymes secretions
a rise in Ca triggers secretions
pancreatic ductal cells
HCO3, Cl, Na, H20, and H+
modifies: absorbing Cl-, secreting HCO3 via Cl-HCO3 exchanger
HCO3 produced by carbonic anhydrase
Cl diffuses by CFTR channel
NKCC transporter provides Cl too
Na and H2O:
passively move by para-cellular pathway
H+:
formed with HCO3 in the cell
exits across basolateral membrane via Na-H exchanger
Low flow and high flow?
Low flow:
from acinar cells
mainly NaCl
High flow:
from ductal cells
mainly NaHCO3
cystic fibrosis and pancreatic secreting cells
defective CTFR channel
less Cl- secretion lower lumen negativity decreased Na and H2O movement decreased ductal secretions decreased enzyme secretion = malabsorption
pancreatic secretions: cephalic phase
food stimulus = increased vagal nerve activity via Ach
increased vagal nerve activity = increased activity from acinar cells and ductal cells
increased secretion of enzymes and HCO3 secretion
pancreatic secretions: gastric phase
food in stomach =
gastric distension = increased vagal response = Ach receptors = enzyme release (acinar cells)
gastric secretion = increased gastrin = CCKb receptor activation = enzyme release (acinar cells)
protein in food = increased CCK = activation of CCK receptors = enzyme secretion (acinar cells)
distal colon and NaCl absorption
when the body has low Na levels
aldosterone stimulates the ENaC pump to promote Na retention
aldosterone also enhances K excretion
K moves passively (normal)
secretory diarrhea
increased endogenous secretions of fluid and electrolytes from GIT
usually due to bacterial toxins, tumors, or hormones
Diarrhea and K
increases rate of fluid loss into the GIT leads to a loss of K
can lead to hypokalemia
