Block 4 Flashcards
vitamin A is also known as
retinol
the natural forms of vitamin A are __ and __
retinol
beta-carotene
the active forms of vitamin A are __ and __
retinal
retinoic acid
what are the 3 main functions of vitamin A
vision (retinal pigments)
gene transcription
differentiation of epithelial cells into specialized tissue
what are the common food sources of vitamin A
liver/kidney
butter
egg yolks
orange/yellow fruits/veggies
dark green vegetables
vitamin D is also known as
calciferol
When active in the kidneys= calcitriol
the active form of vitamin D in the kidneys is
calcitriol aka 1,25 di (OH)- vitamin D3
what is the storage form of vitamin D
calcidiol aka 25-hydroxy vitamin D2
what are the main functions of vitamin D
Ca/PO4 homeostasis
vitamin E is also called __
tocopherol
the 2 forms of vitamin E are __ and __
tocopherol
tocotrienol
the main function of vitamin E is to serve as a __
antioxidant
what are the functions of vitamin K
activation of clotting factors II, VII, IX, and X
use in ETC
osteocalcin bone formation
vitamin B1 is also known as __
thiamine
vitamin B2 is also known as __
riboflavin
vitamin B3 is also known as __
niacin
vitamin B5 is also known as __
pantothenic acid
vitamin B6 is also known as __
pyrixidine, pyridoxal, or pyridoxamine
vitamin B7 is also known as __
biotin
vitamin B9 is also known as __
folate
vitamin B12 is also known as __
cyanocobalamin or methylcobalamin
what 4 enzymes use vitamin B1 (thiamine)
alpha-ketoglutarate
transketolase
pyruvate dehydrogenase
branched chain ketoacid dehydrogenase
what is the function of vitamin B2 (riboflavin)
used as a precursor to coenzymes FAD and FMN used in redox reactions (dehydrogenase and reductase enzymes)
what is the function of niacin (vitamin B3)
a precursor of NAD and NADP
what is the function of vitamin B5 (pantothenic acid)
it’s a precursor of coenzyme A for FA, cholesterol, and acetylcholine synthesis
what is the function of vitamin B6
the active form, pyridoxal phosphate, is used in the metabolism of alcohols, fats, and proteins
(heme and neurotransmitter synthesis, transamination, amino acid decarboxylation)
what is the function of vitamin B7 (biotin)
used as a cofactor with carboxylase enzymes
what is the function of vitamin B9 (folate)
precursor for methionine, purine, and pyrimidine synthesis, conversion between serine and glycine, and degradation of histidine to glutamate
what is the function of vitamin B12 (cobalamin)
methionine synthesis
folate metabolism
maintenance of myelin sheath
RBC maturation
what is the function of vitamin C (ascorbate)
used as a cofactor for hydroxylases
enhance iron absorption
norepinephrine formation
what amino acid load test is used to test for folate deficiency
histidine
what 2 vitamins are stored in the liver
B9 and B12
B12 absorption requires functioning __, __, and __ (what organs)
stomach
pancreas
ileum
what is produced in the stomach by parietal cells that is needed in the absorption of vitamin B12
intrinsic factor
before vitamin B12 is internalized for absorption, it binds to IF, forms a complex, then binds to __ receptor
cubilin
what is the main extracellular cation
Na+
what is the main intracellular cation
K+
what is the main extracellular anion
Cl-
what is the main intracellular anion
phosphate
what are the 3 main functions of sodium
nerve transmission
muscle function
control body osmolarity
the main function of potassium is to regulate __ and it is primarily regulated by __
heart rate
aldosterone
respiratory acidosis is caused by __
metabolic acidosis is caused by __
hypoventilation
uncontrolled diabetes, diarrhea, lactic acid, kidney disease (non-respiratory cause)
respiratory alkalosis is caused by __
metabolic alkalosis is caused by __
hyperventilation
antacids, vomiting, etc.
what is the main function of magnesium
regulate calcium
what are the 3 major iron containing proteins
hemoglobin
myoglobin
cytochromes
is heme iron Fe2+ or Fe3+
Fe2+
heme iron (Fe2+) is absorbed directly into intestinal cells. what must occur with non-heme iron before it is absorbed
it must be reduced to Fe2+ first
__ decreases absorption of iron
__ increases absorption of iron
calcium decreases
vitamin C increases
in low cellular iron cases, there is an increase in __ synthesis to help transport the iron into the cell
transferrin receptor
in high cellular iron cases, there is an increase in __ synthesis to bind the surplus iron and a decrease in __ synthesis
ferritin
transferrin receptor
what are the effects of excessive free iron
can lead to oxidative stress due to free radical generation
what is iodine required for
formation of thyroid hormone
what are the 6 trace elements/minerals
iron
iodine
selenium
sulfur
copper
zinc
what 4 enzymes use TPP (thiamine)
Alpha ketoglutarate dehydrogenase
Transketolase
Pyruvate dehydrogenase
Branched chain ketoacid dehydrogenase
what are the 3 main symptoms of infantile Beri Beri
cyanosis
tachycardia
cardiomegaly
what are the 3 main symptoms of wet Beri Beri
cardiomyopathy
pitting edema
tachycardia
what are the 3 main symptoms of dry Beri Beri
no edema
muscle atrophy
bilateral peripheral neuropathy
what are the 5 main symptoms of riboflavin (vitamin B2) deficiency
glossitis
cheilosis
seborreic dermatitis
stomatitis
normocytic normochromic anemia
what is the main symptom of high riboflavin
bright yellow-orange urine
what are the 3 main symptoms of niacin (vitamin B3) deficiency
dementia
diarrhea
dermatitis (scaly skin exposed areas)
a diet high in __ can lead to vitamin B3 deficiency
corn/maize
what are the 4 main symptoms of niacin (vitamin B3) toxicity
skin flushing
hyperglycemia
hypocholesterolemia
hyperuricemia
what are the 4 main symptoms of vitamin B6 deficiency
cheilosis
stomatitis
skin rash
hypochromic microcystic sideroblastic anemia
what are the 5 main symptoms of biotin (vitamin B7) deficiency
hair loss
scaly facial rash
depression
conjunctivitis
hypotonia/lethargy
what are the 6 main symptoms of folate (vitamin B9) deficiency
homocystinuria
atherosclerosis
hypersegmented PMN
glossitis
diarrhea
macrocytic/megaloblastic anemia
what are the 3 main symptoms of vitamin B12 deficiency
tingling/numbness in limbs
methylmalonic acid toxicity
macrocytic/megaloblastic anemia
riboflavin (vitamin B2) is used in what two types of enzymes
dehydrogenase
reductase
vitamin B6 is used for what 5 types of reactions
transamination
amino acid decarboxylation
heme synthesis
neurotransmitter synthesis
niacin (vitamin B3) synthesis from tryptophan
biotin (vitamin B7) is used with what type of enzymes
carboxylase
what are the 3 molecule requirements for hematopoiesis
iron
vitamin B12
folic acid
deficiency in 1 of what 3 molecules can lead to anemia
iron
vitamin B12
folic acid
what hormone directs the differentiation into erythrocytes
erythropoietin
what hormone directs the differentiation into platelets
thrombopoietin
what secondary condition is present in any kidney failure patient
anemia
erythropoietin is synthesized in the __ of the __ in response to __
peritubular capillaries
renal cortex
hypoxia
if a patient has kidney failure, what hormone level is going to be low
erythropoietin
erythropoietin uses what class of receptors
JAK/STAT (JAK2-STAT5)
what is supplemented in cases of renal failure
erythropoietin
how do immature erythrocytes differ from mature erythrocytes
immature have organelles
mature do not
why can RBC not use anything other than glucose for an energy source
they don’t have the necessary organelles (mitochondria) to break down FA/ketones
what is the most predominant iron containing molecule
heme
what is the structure of a hemoglobin molecule
2 alpha chains
2 beta chains
4 heme groups
what is the structure of a heme molecule
Fe2+ in the center surrounded by 4 porphyrin rings
where does heme biosynthesis occur
mitochondria and cytoplasm
besides heme synthesis, what other process occurs in the mitochondria and cytoplasm
urea synthesis
what 2 main molecules build heme
succinyl CoA
glycine
what TCA cycle intermediate is needed for heme synthesis
succinyl CoA
what amino acid is needed for heme synthesis
glycine
what cofactor is used in heme synthesis
pyridoxal (B6)
what enzymes of heme synthesis are present in the mitochondria
ALA synthase
ferrochelatase
what is the rate limiting enzyme of heme synthesis
ALA synthase
a deficiency in what 3 molecules can lead to microcytic anemia
iron
B6
vitamin C
why can a deficiency in vitamin C lead to microcytic anemia
vitamin C is needed to reduce iron to an absorbable form
a deficiency in what 2 molecules can lead to macrocytic anemia
vitamin B12
folate (B9)
porphyira conditions involve a deficiency in what
enzyme in heme synthesis
in heme synthesis, what enzymes does lead inactivate
ferrochelatase (last enzyme)
ALA dehydratase (2nd enzyme)
what accumulates with defect in ALA dehydratase (can result due to lead poisoning)
aminolevulinic acid (ALA)
in lead poisoning, Fe is not added to form heme. what is added instead to whatever protoporphyrin IX that has already been made
zinc
what is the lab reading for someone with lead poisoning (3 results)
ALA in blood/urine
elevated zinc protoporphyrin levels
basophilic stippling (dots in RBC)
what exposure is associated with a risk in lead poisoning
urban, old house
lead based paint
what is the main symptom of lead poisoning
developmental delay or regression
*young children more susceptible due to under developed BBB and ingestion
What is a cause of iron deficiency anemia
lead poisoning
what enzyme is deficient in acute intermittent porphyria
porphobilinogen deaminase/hydroxymethylbilane synthase/uroporphyrinogen I synthase
(multiple names for the same enzyme)
what accumulates in acute intermittent porphyria
ALA
porphobilinogen
what are the 4 main symptoms of acute intermittent porphyria
abdominal pain (although all abdominal exams are normal)
neurological manifestations (incorrect psychiatric diagnosis)
no photosensitivity
portwine color urine on sitting
acute intermittent porphyria can be diagnosed through what method
urine dipstick
what medication is never given to those with acute intermittent porphyria
barbituates
what are the symptoms of porphyria cutanea tarde
photosensitivity
shearing of skin in areas exposed to skin (blistering)
what is the most common disorder of porphyrin synthesis
porphyria cutanea tarda
what enzyme is deficient in porphyria cutanea tarda
uroporphyrinogen decarboxylase
what accumulates in blood/urine with porphyria cutanea tarda
uroporphyrinogen III
what 2 molecules are negative regulators of heme synthesis
heme
glucose
heme and glucose act as negative regulators of heme synthesis by inhibiting what part of the synthesis
ALA synthase
how do barbiturates increase heme synthesis
cytochromes (cytochrome P450) are heme requiring so if you give a barbiturate, heme synthesis occurs leading to the buildup of an intermediate
what are the 2 main treatments for porphyrias
ingestion of carbohydrates (glucose)
administer hematin (heme)
a deficiency in __ or __can lead to sideroblastic anemia
ALA synthase
B6
what drug usage should be supplemented with B6
isoniazid for TB
why is B6 supplementation given with isoniazid usage
isoniazid inactivates B6
what is seen in a bloodsmear with someone with sideroblastic anemia
ring sideroblasts (iron accumulates around the developing RBC due to lack of ALA synthesis)
how does CO interfere with heme synthesis
CO competitively binds to iron in heme protein
with Fe2+ bound with CO, there is no O2 exchange
(CO binds with greater affinity than O2)
at the cellular level, CO binds to __, inhibiting aerobic metabolism, leading to tissue hypoxia (in ETC)
cytochrome oxidase (complex IV)
what is the classification of anemia based on
size of RBC (MCV)
what causes microcytic anemia in terms of cell divisions
more divisions= low MCV (low size) due to lack of availability of hemoglobin molecules
what are the 4 reasons for lack of available hemoglobin molecules
iron deficiency
thalassemia (globin chains)
sideroblastic anemia (B6 deficiency)
lead poisoning
what causes megaloblastic anemia in terms of cell divisions
vitamin B12 or B9 deficiency= inability to synthesize new bases= decreased cell divisions
strict vegans are at risk for what main vitamin deficiency
B12
methylfolate trap is due to deficiency in what vitamin
B12
how can B9 be differentiated from B12, when they both show megaloblastic anemia and hypersegmented neutrophils
B12 shows elevated homocysteine and methylmalonic acid
B9 only shows elevated homocysteine
what vitamin is needed for thymidylate synthase for pyrimidine and purine synthesis
B9
folate deficiency inhibits the synthesis of nucleic acids, particularly the formation of ___
deoxythymidine monophosphate (dTMP)
what 2 enzyme defects can lead to hemolytic anemia
G6PD
pyruvate kinase
pyruvate kinase is an enzyme of what pathway
glycolysis
in pyruvate kinase deficiency, what happens with the spleen
splenomegaly
G6PD is an enzyme of what pathway
pentose phosphate pathway
where does heme breakdown occur
reticuloendothelial system in the spleen and liver
what is the breakdown product of heme
bilirubin
what is the main enzyme of heme breakdown
heme oxygenase
heme is broken down into __ and __
Fe2+
bilirubin
when heme is being broken down, Fe is in what form
Fe2+
what part of heme is broken to form bilirubin
alpha bridge
heme oxygenase used in heme catabolism requires what 2 molecules
NADPH
O2
what 2 enzymes produce NADPH
what process are they involved in
G6PD- PPP
FA synthesis- malate dehydrogenase
what enzyme involves the physiological release of O2
heme oxygenase
heme oxygenase of heme catabolism produces what 3 molecules
Fe3+
CO
biliverdin
in heme breakdown, biliverdin is converted to bilirubin through use of what enzyme
biliverdin reductase
biliverdin reductase uses what cofactor
NADPH
bilirubin formation occurs in what organ
spleen
why must bilirubin be transported to the liver bound to albumin
it is insoluble (hydrophobic)
conjugation of bilirubin occurs where
liver
the 3 steps to bilirubin metabolism are
uptake by liver cells
conjugation
secretion in bile
what bilirubin accumulates in kernicterus
unconjugated (insoluble)
where does unconjugated bilirubin deposit in kernicterus
basal ganglia
what happens once the albumin-bilirubin complex reaches the liver
albumin unbinds and re-enters the blood
bilirubin enters the hepatocyte through the bilirubin transporter
once unconjugated bilirubin is in the liver, what is used to trap it and prevent efflux back to the blood
glutathione-S-transferase (GST)/protein Y/ligandin
unconjugated bilirubin in the liver is conjugated by what enzyme
bilirubin-UDP-glucuronosyltransferase (UGT1A1)
what is used to transport conjugated bilirubin into the bile duct
MRP (multi-drug resistant protein)
what molecule is added to conjugate bilirubin in the liver
UDP-glucuronic acid
what is the function of UDP-glucuronic acid in the liver
conjugate bilirubin to make it hydrophilic, allowing for excretion
also used for bond formation
how many time is UDP-glucuronic acid and bilirubin-UDP glucuronyltransferase used in the conjugation step
2
UDP is used in what 2 molecules
UDP glucose (glycogen synthesis)
UDP glucuronic acid (bilirubin metabolism)
what are the 3 causes of jaundice
- hemolytic anemia- more bilirubin production than the liver can excrete due to hemolysis
- defect in liver (no conjugation)
- blockage of bile duct
what allows for reduction of conjugated bilirubin to urobilinogen in the small intestine
bacterial enzyme beta-glucuronidase
urobilinogens are ___
urobilins are __
(colored/colorless change)
urobilinogens- colorless change
urobilins- colored change
how can you assess for anemia/pallor by palpebral exam
pale lower palpebral conjunctiva
how can you assess for jaundice/icterus by palpebral exam
pale upper palpebral conjunctiva
where would you see jaundice most evident
sclera due to white background and high elastin content
pre-hepatic jaundice is caused by __
hemolytic anemia
(ex: sickle cell, G6PD deficiency, glutathione reductase deficiency)
hepatic jaundice is caused by __
liver disease
post-hepatic/obstructive jaundice is caused by __
gallstones or pancreatic cancer
is the level of direct (conjugated) or indirect (unconjugated) bilirubin higher in the serum
indirect (unconjugated)
is urinary bilirubin conjugated or unconjugated
conjugated
serum levels of what 2 enzymes indicate hepatitis
alanine aminotransferase (ALT)
aspartate aminotransferase (AST)
serum levels of what enzyme are increased in obstructive liver disease
alkaline phosphatase (ALP)
what is the stool presentation in obstructive liver disease/cholestasis
clay colored stool
why is alkaline phosphatase (ALP) level raised in post-hepatis jaundice
the liver pumps bile juices into the bile duct but they get blocked. this causes bile acids to form micelles and ALP is released
what are the 3 lab values for hemolytic jaundice
increased indirect (unconjugated) bilirubin
–>increased direct (conjugated) bilirubin
increased urine urobilinogen
increased fecal stercobilin (urobilinogen)
why is the urine dark yellow in both hemolytic jaundice and obstructive jaundice
bilirubin is in the urine
what color is the stool as a result of hemolytic jaundice
dark brown
what are the 3 lab values of obstructive/post-hepatic/cholestatic jaundice
increased direct (conjugated) bilirubin in blood and urine
low/no urine urobilinogen
low/no fecal stercobilin (urobilinogen)
what is the color of stool as a result of obstructive/post-hepatic/cholestatic jaundice
clay/pale colored (no fecal stercobilin/urobilinogen)
why can unconjugated bilirubin never appear in the urine
it is insoluble/lipophilic/hydrophobic and bound to albumin (large complex)
how does phenobarbital act on bilirubin metabolism
it’s an enzyme inducer so it increases the enzyme activity of glucuronyltransferase in the liver to increase conjugation of bilirubin
what is the main concern of crigler najjar syndrome type I
it leads to encephalopathy that can lead to permanent brain damage within the first year of life
how does phototherapy work for treatment of jaundice
blue light isomerizes trans (unconjugated) bilirubin to soluble cis (conjugated) bilirubin that can be easily excreted
what are 2 processes involved in isomerization
methylmalonyl CoA–>succinyl CoA
trans bilirubin–>cis bilirubin
what process involves epimerization
galactose<–>glucose
what must be supplemented in a neonate receiving phototherapy for jaundrice
vitamin B2 (riboflavin)
B2 is degraded by light
what causes neonatal jaundice
low activity/immature bilirubin-UDP-glucuronyltransferase in the liver to conjugated bilirubin
what is neonate jaundice evident
2-3rd day of life
how can you differentiate Gilbert syndrome from physiological (neonatal) jaundice
Gilberts- later in life and requires a stimulus (stress/fasting/etc.)
physiological- 2-3 days after birth and resolves in 5-7 days
how can bilirubin form gallstones
formed by calcium salts of unconjugated bilirubin
what do you call the gallstones formed by bilirubin salts
pigment gallstones
what is the appearance and texture of pigment gallstones caused by unconjugated bilirubin
soft, dark brown/black
what causes pigmented gallstones to form
bacterial/helminthic infection that causes bacterial beta glucuronidase to be released hepatocytes
(this enzyme is usually only released in the small intestine)
what does beta glucuronidase do when it is released by hepatocytes during a bacterial or helminthic infection
unconjugates bilirubin in the liver after our enzymes have already worked to conjugate it
how does plasma differ from serum
plasma contains fibrinogen, serum does not
what is the main blood plasma protein
albumin
where are most plasma proteins synthesized
liver
most plasma proteins are synthesized in the liver with the exception of __ which is synthesized in __, and __ which is synthesized in __
von Willebrand factor
vascular endothelium
gamma globins
lymphocytes
most proteins are covalently modified by the addition of N or O linked oligosaccharide chains, or both. what plasma protein is an exception to this
albumin
what plasma protein is responsible for osmotic pressure of human plasma
albumin
what plasma protein contains disulfide bonds
albumin
what 3 molecules can be used to access liver function
AST and ALT liver enzymes
bilirubin
albumin
what 3 molecules can be used to access kidney function
creatinine
urea (make sure to account for protein diet history)
albumin
what is the best and 1st indicator of kidney disease
albumin in the urine
(typically, albumin is not filtered due to it being of the same charge and size of the glomerular filtration membrane. when there is an issue in the membrane, changing the charge, albumin is allowed to be filtered into the urine)
what are the 3 main functions of albumin
plasma osmotic pressure maintenance
transport
buffering
does albumin level relate to edema
decrease in plasma albumin= decreased in osmotic pressure= fluid buildup in tissues= edema
what is one of the main symptoms of kwashiorkor
decreased albumin–>edema
how is albumin able to act as a buffer
high histidine content
why is albumin more important than globins in the plasma
albumin has buffering capability
how does albumin relate to BBB maintenance
albumin binding to other molecules forms a large complex, preventing them from crossing the BBB
hypoalbuminemia in what 3 conditions leads to edema
malnutrition
nephrotic syndrome (any kidney disease)
liver cirrhosis
albumin is useful in treatment of __ and __
burns
hemorrhage
what is the normal albumin:globin ratio in blood plasma
1.2-1.5:1
what blood plasma protein protects the kidneys from damage by extracorpuscular hemoglobin/iron
haptoglobin
what type of protein is the plasma protein haptoglobin
acute phase
what are acute phase proteins
nonspecific proteins activated by inflammation
haptoglobin levels are low in what condition
hemolytic anemia
__ binds heme
__ binds hemoglobin
hemopexin binds heme
haptoglobin binds hemoglobin
what is the importance of high C reactive protein levels
it indicates inflammation
what are the 5 positive acute phase proteins (what plasma proteins are increased)
ferritin
fibrinogen
serum amyloid A
hepcidin
C reactive protein
what are the 2 negative acute phase proteins (what plasma proteins are decreased)
albumin
transferrin
why is CRP (C reactive protein) named with a C
it reacts with C polysaccharide
