exam 3/final exam Flashcards
What percent of bone cells are living? What percent are non-living?
2-5% are Living
95-98% are Non-Living, mineral encrusted protein-matrix (osteoid)
What is osteoid?
the mineral encrusted protein- matrix of nonliving material in bone
What are osteocytes?
they are master regulators that have processes that come out of their cell bodies
They reside in the matrix lacunae(space) and communicate through cellular processes
The canaliculi are microscopic canals of the osteocyte lacunae
70% of total bone is what?
carbonate hydroxyapatite
Calcium, phosphate and carbonate
40% of bone weight is calcium
the protein matrix consists of what percent collagen?
90%
Collagen is a single strand triple coil building mineral content on top of each other
10% is noncollagenous organic matrix
What are the four types of bone cells?
lining cells
osteoblasts
osteoclasts
osteocytes
osteoporosis is characterized by what?
decreasing mineral content on bones and getting weaker
Osteocytes do what?
they are master regulator cells that communicate other functions of other cell types (osteoblasts and osteoclasts)
Osteoblasts differentiate from osteoclasts how?
osteoblasts Build up minderal content (downregulated as you age but still functions)
Osteoclasts demineralize and break down mineral content
what do lining cells do?
they provide barriers of bone
What are inborn errors of metabolism?
large group of rare disorders caused by inherited deficiency or absence of proteins that have enzymatic, carrier, receptor or structural roles
For many, the molecular nature of the disorder is known
Responds to nutrient therapy intervention
Those most frequently identified disorders are those in which the absent or defective protein does what?
serve an enzymatic function
What are some examples of inborn errors of metabolism?
phenylketonuria Galactosemia Glycogen Storage disease homocystinuria Maple syrup urine disease branched chain ketoaciduria
In mutant DNA, what happens to the protein?
defects in structure/activity of protein, block normal flow of metabolic processes
what is the pathophysiology of inborn errors of metabolism?
accumulation, deficiency or overproduction of normally occurring substrates and products of metabolic flow
What is the diagnosis for inborn errors of metabolism?
symptoms presented by infants, lab analysis confirms biochemical and DNA analysis
What is the treatment for inborn errors of metabolism?
nutritional intervention modifies components of diet to correct the metabolic imbalance
What happens when you modify the components of diet to correct the metabolic imbalance?
you decrease the substrate available for the reaction, supplement the product to normal level, and enhance the enzyme activity by supplying its co-factor
What are the three assessments done in nutritional assessment and monitoring?
growth
nutrient intake
biochemical paramters
Why is there a variable outcome when treating inborn errors of metabolism?
depends on early diagnosis and intensive and continuous intervention
what alleviates toxic manifestations in inborn errors of metabolism?
modification of the dietary supply
What prevents poor outcome in the clinical characteristics of inborn errors of metabolism?
early diagnosis and early treatment
irreversible damages could occur if you do not
What is phenylketonuria (PKU)?
group of inherited autosomal recessive disorders of phenylalanine metabolism associated with impaired ability to convert phenylalanine to tyrosine
What are the causes of PKU?
inherited defects in :
phenylalanine hydroxylase (PAH) which is classic PKU
dihyydrobiopterin reductase (DHPR) dhydrobiopterin biosynthesis
What is the pathogenesis of PKU
> deficiency of Tyr causes CNS damage
deficient myelination (non treated causes are impaired brain development and irreversible)
abnormalities in brain proteolipids and/or proteins
depressed protein synthesis
imbalance in intraneuronal amino acid concentration
when does pku express itself in children?
3 months of age
developmental delay, abnormal electroencephalogram, musty odor
What is the blood phenylalaline level?
> 2 mg/dL`
What is the diagnosis for pku?
plasma aa anaylsis
dna diagnosis
family history prenatal diagnosis
genotyping of parents, carrier detection
Treatment of PKU?
maintain blood Phe to prevent CNS damage
restricted diet
start as soon as diagnosis is established within 3 weeks of age
optimal blood phe is 60-300 µmol/L
tyrosine supplement
adequate energy, protein and other nutrients
What is galactosemia?
a group of inherited autosomal recessive disorders of galactose metabolism
What are the causes of galactosemia?
defects in three enzymes
- Galactose 1-phosphate-uridyl transferase (GALT)
- galactokinase
- 4-epimerase
What is the pathophysiology of GALT deficiency?
accumulation of Gal-1-P –> reduce ATP, GTP, and CTP
inhibit galactation of phospholipids
UPD-Gal deficiency, accumulation of galactose and its byproducts affect intracellular osmolality
What are symptoms of gal-1-p (gal-1-puridyltransferase)?
classic galactosemia (cataracts, growth failure, mental retardation, liver failure)
if both mom and dad are carriers of galactosemia, what is the percentage breakdown of acquiring the disorder?
50% carrier
25% galactosemia
25% neither
if galactosemia is untreated?
hepatoxicity (hyperbilirubinemia, hepatomegaly, cirrhosis)
infection and sepsis: impaired immune infections
kidney damages
CNS damage: mental retardation
growth failure
Galactosemic infants given milk leave it unmetabolized and sugars build up to damage the liver, kidneys and brain
diagnosis of galactosemia?
newborn screening,
biochemical analysis: GALT activity, GAL-1-P
DNA analysis
prenatal exam: GALT enzyme check
treatment of galactosemia?
prevent symptoms and support growth and development
Galactose restricted diet
Provide enough energy, protein and other nutrients
What is the galactose restricted diet?
AVOID ALL OF THESE:
remove all sources of galactose and lactose from diet
formula: soy milk
ACCEPTABLE:
fruits, cereals, legumes, nuts, and vegetables are acceptable
What is branched chain α-ketoaciduria (Maple syrup urine disorders)?
a group of hereditary autosomal recessive disorders of Ile, Leu, and Val metabolism, which is caused by imapired branched-chain α-ketoacid dehydrogenase
What is the incidence rate of α-ketoaciduria, galactosemia, and phenylketonuria?
α-ketoaciduria 1:180k galactosemia 1: 20k phenylketonuria . 1:15k
What are the clinical characteristics of α-ketoaciduria?
clinically normal until after eating dietary protein
Increased BCKA and BCAA (branched achain amino acid) in blood, urine and cerebrospinal fluid
fragrant urine with odor of maple syrup
progressive neurological dysfunction: deficient myelination
non-treated Maple Syrup Urine Disorder causes death (20%) or permanent neurological damage
Diagnosis of Maple syrup urine disorder aka branched chain ketoaciduria?
newborn screening leucine > 4mg/dL
plasma and urinary val, leu, ile, and BCKA
enzyme activity
DNA analysis
treatment for branched chain ketoaciduria?
prevent accumulation of neurotoxic BCKAs
maintain plasma BCAA at optimal level
thiamin supplement: stabilize the enzyme complex
high energy intake prevents protein catabolism
Von Gierke’s Disease Type I
glycogen storage disease details?
age of onset: newborn 3-4mo
glucose-6-phosphatase enzyme deficiency: enzyme responsible for cleaving off PO4 from glucose
liver and kidneys affected
REQUIRED to obtain glucose to be released into circulation from liver glycogen and glucogenesis
growth retardation,
UNTREATED: hypoglycemia and hyperlipidemia
how to treat von gierke’s Type I disease?
constant supply of carbs to prevent glucogenesis and lipolysis
calcium is a large nutrient reserve for which two minerals?
calcium in form of calcium homeostasis
phosphorous
depends on daily intake and excretion
bone mass depends on a variety of what nutrient factors?
genetics
mechanical loading
hormonal status
low bone mass always signifies reduced ____ reserve
calcium
difference between gp cartilage and articular cartilage
glycoproteins in gp cartilage and smooth white tissue covering ends of bones in articular cartilage
origin of osteoclasts
hemopoietic stem cell -> monocytes/monocyte lineage -> osteoclast multinucleated
origin of osteoblasts
stem cells > mesenchymal stem cells > pre-osteoblasts/osteoblasts/osteocytes
other names for cortical bone and trabecular bone are _____
cortical bone = compact bone
trabecular bone = spongy bone
why do weight bearing bones have different percentages in trabecular and cortical bone?
bone that bears more weight must be flexible
Ex. ribcage is >75% trabecular spongy bone
What are the MAJOR nutrients influencing skeletal metabolism?
Ca, P, Vit D – rickets, bone mineralization
REtinoic Acid – Limb development
Cu – cartilage dysplasia, collagen, cross-linking
Zn – dwarfism
Other mineral deficiencies that can be associated with skeletal system deficiency
What are the MINOR nutrients influencing skeletal metabolism?
B, F, Sr – osteoporosis, stimulate osteoblast activity
Se – skeletal growth
Vitamin K - osteoporosis
Ascorbic acid – skeletal matrix, collagen
calcium contrasts with majority of other nutrients. How does this lead to disease?
other nutrients have reserves, which are depleted first with no impact on biochemical function
after reserve is depleted, metabolic pool used is exhausted –> disease
Calcium has VAST RESERVE and biochemical pathways not impaired but bone strength dependent on bone mass so DECREASE IN CALCIUM RESERVE IS DECREASE IN BONE STRENGTH
Why does reabsorbtion occur in the skeleton during menopause, anorexia nervosa, and athletic amenorrhea?
skeleton sense more bone than it needs for reabsorption occurs to greater extent than formation
regular menstruation is the key to calcium maintenance in who?
young women, but same phenomenon occurs in men when testosterone is lacking
when are bending setpoints of skeleton high and low?
level of gonadal hormones determinant
high at puberty
low at menopause
what does vitamin D do in relation to calcium?
promotes absorption of calcium, development of healthy bones and teeth
WHAT IS THE METABOLICALLY ACTIVE VITAMIN D?
dihydroxyvitamin D3
^ calcium absorption in small intestine
^ urinary calcium re-absorption in kidney
^bone mineralisation
MAINTAINS CALCIUM BALANCE IN THE BODY VIA THE ACTION OF PARATHYROID HORMONE
rickets occur from deficiency in what nutrients?
calcium and vit D
mass and density of bone affected by what three factors?
nutrition
physical activity
gonadal hormones
Osteoporosis is defined as what
condition of skeletal fragility due to decreased bone mass and to microarchitectural deterioration of bone tissue, with consequent increased risk of fracture,
not a single disorder but a group of discrete fracture syndromes
what are causes of osteoporosis?
increased activity of osteoclasts in response to estrogen deficiency,
decreased activity of osteoblasts and
rate or trabecular and cortical bone resorbtion exceeds bone formation
minor factors contributing to osteoporosis
family history
physical inactivity
fair complexions
inadequate calcium and vitamin D intake
*what happens when your bones sense downregulation in estrogen level?
hemopoietic stem cells increase in cell differentiation and transform into osteoclasts, and thus overall increasing osteoclast activity
TOP THREE INFLUENCING FACTORS IN DEVELOPMENT OF OSTEOPOROSIS
BONE DENSITY DECLINES
nutrition (calcium, vit D, acid base balance)
Hormonal (growth hormone, estrogen, corticosteroids)
what is the difference in macronutrient intake and obesity over the years?
carb and fat intake increase with refined food fast food increase from 1970s to now
liquid carbs poor compensation with solid carbs
what is difference in rats and humans for compensation?
misrepresent and overeat in form of beverage versus rats, who do sense the calories and stop eating
the research on rats – procedure for calorie comepnsation
Performed hippocampal memory tests only after he stopped giving them
Gave rats the beverages ony during teenage years of three weeks and stopped when they became adults
Didn’t gain anymore weight and performed poorer
Take home message: maintenance or overconsumption of beverages causes impairments in cognitive functions later in life
Actual human children maintained on these drinks have impairments in cognitive function
Giving them the beverage as adults had no affect but does in adolescence development it does
the western diet consumption and cognitive impairment has links to what?
hippocampal dysfunction and obesity
percentage breakdown of artificial sweeteners
aspartame -- 55 sucralose -- 13 acesulfame k -- 12 cyclamate --11 sacchasin -- 8 stevia -- 1
most sweeteners a combo of which two sweeteners?
aspartame and ace k
saccharin is 300-500 x sweeter than sugar per gram but what are its other qualities
no food energy and not digested, passes through body unchanged
OLDEST and tastes most artificial
aspartame is 200 x sweeter than sugar and provides how much energy
4 kcal energy per gram, limitations include short shelf life and not stable with eating
gives energy bc it is an amino acid
ace k commonly combined with aspartame or sucralose in beverages and also 200x sweeter than sugar but what other qualities
not metabolized, excreted unchanged
sucralose 800x sweeter than sucrose but other qualities are
stable under heat
not accidental discovery; made from sugar and substitutes 3 hydroxyl groups with chlorine: safe bc chlorine does not separate from sucralose
weight gain or loss from consuming artifical sweetened beverages
greater risk of weight gain and increased bmi
CORRELATION NOT NECESSARILY CAUSALITY
Association of weight gain
Increase in ingestion of beverages and sweeteners went up over the years
Increase in frequency of obesity
no CONSISTENT evidence that ASB intake is associated with weight loss or gain in human popoulations
cck satiation signals
accumulation of chemical inhibitory signals that eventually causes satiety within the meal for meal termination, largely arising form the GI tract. Meal initiation is primarily the result of an absence of satiating signals.
liraglutide and exendin
rgalutide only drug approved to treat obesity, exendin treats diabetes
liraglutide meets 5-10% sustained weight loss but exendin does not. *liraglutide meets it but plateaus
