Pulmonary Biochemistry Week 3 Flashcards Preview

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Flashcards in Pulmonary Biochemistry Week 3 Deck (189):

True/False: Respiratory acidosis/alkalosis are always caused by abnormal function of the lung

FALSE - often but not always. For example, a person can have respiratory acidosis (increased PaCO2) but lungs are normal


On the davenport diagram, the x-axis represents ____ and the y-axis represents _____ therefore any point on the graph is a solution of the Henderson equation. Overall, the Davenport diagram tells you how blood will respond to changes in ______

pH, [HCO3-], PaCO2


Davenport diagrams reflect the presence of _______ buffers in the blood

non-volatile [presence of Hb mitigates increase in h+ caused by shifts in bicarbonate buffer system]


On a davenport diagram, a steeper buffer line of blood [the line reflecting the changes paCO2 have on pH and HCO3-], would indicate what?

more non-volatile buffering power [basically, with greater changes in PaCO2 there are slightly greater changes in HCO3- but lesser changes in pH so line is steeper]


Describe three non-pulmonary causes of acute respiratory acidosis

disruption in neural linkage driving breathing, central nervous system depression[drug OD, anesthesia], external enviro preventing normal breathing[heavy weight]


Name 5 pulmonary causes of acute respiratory acidosis

upper airway obstruction, severe asthma attack, COPD, severe pneumonia, severe pulmonary edema


Respiratory acidosis/alkalosis is caused by a pathological change in _____ whereas metabolic acidosis or alkalosis is caused by a pathological change in ______

PaCO2, [HCO3-]


With a decrease in CO2 in which direction will the equilibrium shift. How do Hb buffers play a role.

For reference, the rxns:
CO2 H+ + HCO3-
H+ + Hb H+Hb

The equilibrium will shift towards the left to produce more CO2. H+ will be lost, but this will be mitigated by Hb releasing H+.


______ is caused by an increase in central drive to breathe

Respiratory alkalosis


True/False: For respiratory alkalosis to occur, the entire neuromuscular chain for breathing must be intact



What are four conditions that act as abnormal ventilatory stimuli to increase central drive to breathe?

1) arterial hypoxemia or hypoxia; 2) direct stimulation of pulmonary mechanoreceptors and chemoreceptors by lung dz; 3) chemical or physical factors that stimulate the medullary respiratory center; 4) psych factors


True/False: Most common pulmonary diseases can lead to respiratory alkalosis



Describe the three conditions of acute asthma that act as abnormal ventilatory stimuli to increase breathing

Stimulation of sense receptors; anxiety (psych); hypoxemia


Describe the three conditions of pulmonary embolus that act as abnormal ventilatory stimuli to increase breathing

stimulation of sense receptors; pain (psych); hypoxemia


Describe the four conditions of bacterial pneumonia that act as abnormal ventilatory stimuli to increase breathing

inflammatory debris [direct stimulation of mechano/chemo receptors]; fever [direct stimulation of mechano/chemoreceptors]; anxiety [psych], and hypoxemia and hypoxia


How does hypoxemia cause respiratory alkalosis?

The peripheral chemoreceptors in the carotid and aortic bodies begin to drive breathing when PaO2 falls below ~60mmHg [so then CO2 blown off]


The same diseases that cause respiratory alkalosis can cause respiratory acidosis. What two factors would allow the transition to acidosis to occur?

If the disease progresses to a point of severity when MUSCLE STRENGTH IS WEAKENED AND/OR LOAD IS INCREASED enough to "tip the balance"

Load=airflow resistance, lung stiffness, ventilatory requirement
Strength=central drive, neural linkage, resp muscles [4 abnormal ventilatory stimuli]


In end-stage liver disease, ________ is quite common. This disease leads to intrapulmonary shunting that causes low V/Q regions. Pt's will be _____ and have a high A-a gradient

hepatopulmonary syndrome, hypoxemic


Respiratory acidosis is caused by _______ via __________ whereas respiratory alkalosis is caused by ________ via _________

hypercapnia, alveolar hypovenilation, hypocapnia, alveolar hyperventilation


Describe what occurs when a strong acid is added to a blood sample [open to chamber containing CO2 gas at 40mmHg]

Reference rxn: CO2 H+ + HCO3-

Adding H+ will shift equilibrium to left. HCO3- consumed to consume of of added acid. PCO2 will remain at 40mmHg.


Describe what occurs when a strong base is added to a blood sample [open to chamber containing CO2 gas at 40mmHg]

Reference rxn: CO2 H+ + HCO3-

Strong base [A-] will react with H+ to form HA. Therefore, H+ used up. To replace H+, equilibrium shifted to the right. HCO3- increases. PCO2 remains at 40mmHg.


What are two main causes of hypobicarbonatemia [which leads to metabolic acidosis]?

increase in EAP, reduced net excretion due to renal defects

[increase in EAP can be due to derangements in gut function, derangements in metabolism, exogenous intoxicants]


Describe how diarrhea or laxative abuse is a gastrointestinal cause of metabolic acidosis.

Diarrhea and laxative abuse lead to an increase in stool volume which means a lot of HCO3- is lost from the body. The lower gut cells secrete more HCO3- to replace the lost HCO3- which leads to increased H+ secretion into the blood. The increased H+ secretion into the blood leads to blood HCO3- being consumed.


Metabolic acidosis is caused by an imbalance between _______ and ______

organic acid production, consumption


Normally, there is an incomplete metabolism of carbs and lipids. Carbs and lipids are metabolized to organic acids, but do not finish complete metabolism to A- and H+. What is needed to complete this metabolism?



What happens during hypoxia in regards to carb/lipid metabolism?

Carb lipid metabolism is incomplete so there is a build up of organic acids [along with protons]

examples -metabolic acidosis (strenuous exercise with volume depletion) and ketoacidosis (type I diabetes)


______ and _____ are two alcohols that get metabolized to acids and therefore are exogenous causes of metabolic acidosis

methanol, ethylene glycol [essentially dissociate into A- + H+ and will be EAP like]


How does vomiting or nasogastric drainage cause metabolic alkalosis?

H+ are being lost which means that upper GI is generating more H+ --> upper GI is secreting more HCO3- into the blood --> initially, body will dump HCO3- via urine to keep pH normal --> if vomiting/nasogastric drainage continues, will result in metabolic alkalosis


What two mechanisms are required for metabolic alkalosis to occur?

A generation mechanism [such as vomiting] and a maintenance mechanism [such as increase in renal threshold for HCO3- spillage]


Virtually all causes of metabolic alkalosis present with hypokalemia or at least a low-normal K+. Why?

1) H+ moved out of cells to relieve alkalosis which means K+ moves into cells, reducing K+ concentration in plasma
2) Volume depletion increases aldosterone levels --> more Na+ reabsorbed and K+ secreted --> more K+ loss via kidneys


What are the three main factors responsible for maintenance of metabolic alkalosis?

volume depletion, hypokalemia, aldosterone excess


What are the two mechanisms by which loop diuretics and thiazide cause alkalosis?

1) Loop diuretics and thiazide block Na/K/Cl and Na/Cl transporters in the nephron. Therefore there is more Na+ and Cl- which leads to saline diuresis. Later in the nephron, some Na+ is reabsorbed which increases K+ secretion. This drives the nephron in a later segment to reabsorb K+ which leads to H+ secretion. This results in increased H+ loss. I
2) Greater K+ excretion makes the body hypokalemic, so K+ moves out of the cells to compensate which drives H+ into the cells, decreasing the H+ plasma concentration.


True/False: In treatment of edema with loop diuretics and thiazide, virtually all of HCO3- contained in the edema fluid is retained leading to alkalosis



Explain the rule of thumb for acute respiratory acidosis in a simple acute disturbance.

pH down by 0.07 and HCO3- up by 1mM = for a 10mmHg change in PaCO2, the condition is acute and has not been compensated


Explain the rule of thumb for acute respiratory alkalosis in a simple acute disturbance

pH up by 0.08 and HCO3- down by 2mM = for a 10mmHg change in PaCO2, the condition is acute and has not been compensated


Does a patient who has a pH of 7.26, a PaCO2 of 60mmHg, and an [HCO3-] of 26 meet the rule of thumb for acute respiratory acidosis?



In terms of acidosis/alkalosis, what does compensation mean?

change in [HCO3-] or PaCO2 that occurs as a result of the primary disturbance


True/False: In acidosis/alkalosis, compensation is never complete, so pH will only approach 7.4



Why are there acute and chronic respiratory alkalosis/acidosis categories, but no distinction for metabolic acidosis/alkalosis?

Respiratory compensation for metabolic conditions occurs very quickly (basically, immediately)


how long does chronic compensation (via renal system) take for a) respiratory acidosis; b) respiratory alkalosis

4 days; 8 days [highly variable]


In respiratory acidosis, how long does mitigation of pH change by equilibration of body buffers take?

10 minutes


Using the rules of thumb, how can you differentiate between chronic and acute respiratory acidosis/alkalosis?

For a 10mmHg change in PCO2, the pH will change more in acute [0.08] than in chronic [0.03]


A patient with severe COPD presents with a pH of 7.38, PaCO2 of 70mmHg, and [HCO3-] of 40mM. What is the likely acid-base disturbance?

The patient does not have acute respiratory acidosis - change in HCO3- is due to primary disturbance PCO2. The renal system has had time to compensate by increasing plasma bicarbonate, which returned pH back toward normal.


A patient with a history of methanol ingestion has a pH of 7.29, HCO3- of 12, and PaCO2 of 26. What is the acid-base disturbance?

pH is very low, HCO3- is low, and PaCO2 is low. Pt has metabolic acidosis [which is rapidly compensated by respiratory hyperventilation which is why PaCO2 is low].


In metabolic acidosis, what is the primary change and rapid compensated change?

Primary change is fall in HCO3-; rapid compensatory change is fall in PaCO2


In metabolic alkalosis, what is the primary change and the compensatory change?

Primary change is rise in HCO3-; compensatory change is rise in PaCO2


If pt has pH of 7.29, HCO3- of 14, PaCO2 of 30, what is acid base disturbane

metabolic acidosis bc bicarb low - note that PaCO2 is lower than nl so the metabolic acidosis has been rapidly compensated


If pt has pH of 7.57, HCO3- of 42, PaCO2 of 47, what is acid base disturbance?

metabolic alkalosis - note that PaCO2 is higher than normal reflecting compensation for high HCO3-


If pt has pH of 7.57, HCO3- of 18 and PaCO2 of 18, what is acid base disturbance

acute respiratory alkalosis - fit rule of thumb for a 10mmHg drop in PaCO2, the pH goes up by 0.08 units


If pH is 7.60, HCO3- is 32, and PaCO2 is 24, what this the acid base disturbance



A severely bulimic woman has pH 7.51, HCO3- of 38, PaCO2 of 49, what is the acid base disturbance?

Pt has metabolic alkalosis with respiratory compensation [this is why PaCO2 is elevated]

Pt fits the rule of thumb for metabolic alkalosis - PaCO2 up by 0.5 to 1mM for each 1mM rise in HCO3-


What are the four electrolytes that are routinely measured and what are normal concentrations?

Na+ (140mM), K+ (4mM), Cl- (100mM), bicarb (24-30mM)


What three pieces of data that are relevant to acid-based disturbances do venous electrolytes provide?

CO2 or total CO2 (often called bicarb); anion gap; potassium concentration


What is the anion gap? [think equation]

[Na+]- ([Cl-] + [CO2])


How is total venous CO2 measured with arterial blood gas?

ABG measures [HCO3-] and is usually calculated from H-H or henderson eqn after measuring pH and PaCO2


How is total venous CO2 measured with venous electrolytes?

labeled CO2 or total CO2 instead of bicarb - measured in mM instead of mmHg bc not a measure of total gaseous CO2 dissolved. This equals close to the CO2 dissolved + [HCO3-]


Venous CO2 is ______ than arterial [HCO3-]

greater; normal venous CO2 range 24-30mM; normal arterial [HCO3-] range 22 to 26mM


What are the unmeasured anions that make up a normal anion gap?

sulfate, phosphate, organic anions, protein


The ____ is used in anion gap calculation whereas the _____ is used in rules of thumb for acid base disturbance

venous CO2 (total CO2); arterial HCO3- (true bicarb)


If a patient has a pH of less than 7.35 and a bicarb less than 24, and the anion gap is less than 12, what type of acid-base disturbance do they have?

non-gap acidosis


What three disorders account for most cases of anion gap metabolic acidosis?

ketoacidosis (alcoholic or diabetic), lactic acidosis), renal failure


_____ and _____ are the predominant anions in ketoacidosis

acetoacetate, beta hydroxybutyrate


______ is the predominant anion in lactic acidosis



Sulfate, phosphate, urate, hippurate are the premoninant anions in _______

renal failure [normal excreted by the kidney]


_______ is a product of anaerobic metabolic and increased with ______

lactic acid; hypoxia


what are the two most common causes of lactic acidosis?

circulatory failure (cardiogenic shock) and sepsis (septic shock)


What three conditions would be produce an overproduction of ketoacids?

diabetic (usually type1); starvation; alcoholic (drinking and vomiting binges)


What are the three disorders that account for most cases of non-anion gap metabolic acidosis?

diarrhea, renal tubular acidosis, renal failure (chloride from increased chloride retention)


True/False: Renal failure is the most common cause of non-anion gap metabolic acidosis?

FALSE - diarrhea


What are the two sites of heme biosynthesis?

erhythroid cells (~85%) and hepatocytes (~15%)


True/False: heme and iron metabolism are tightly coupled



Heme is composed of ____ and _____

Fe2+, protoporphyrin IX


Hypoxia stimulates eryhthropoiesis which requires ____, ____ and _____

iron, Hb, heme


In the bone marrow, multipotential hematopoietic stem cells give rise to ______ that then divide into _____

erythroid progenitors, erythroblasts


After the _______, the erythyroid cell leaves bone marrow as a ______

expulsion of the nucleus, reticulocyte


What organelles do reticulocytes lose? [nucleus already lost]

mitochondria, ribosomes


Mature erythrocytes participate in what 3 metabolism processes?

glycolysis, pentose phosphate shunt, reductive capacity


Describe how hypoxia and normoxia affects HIF-1 postranslational regulation

If hypoxic, HIF-1 transcription factor is phosphorylated which allows translocation to nucleus where it causes transcriptional activation of oxygen-regulated gene expression.

If normoxic, HIF-1 is ubiquitylated then degraded via proteasome


The enzyme _______ is involved in the "oxygen sensing mechanism" that adds an OH to HIF-1 if in normoxic environment

prolyl hydroxylase


What are the four HIF-1 target genes involved in erythropoiesis and iron metabolism?

EPO, transferrin, transferrin receptor, ceruloplasmin


______ is involved in iron uptake

transferrin receptor


______ is involved in iron oxidation and release of iron from stores



_____ is involved in iron transport



What does HIF-1 stand for and what is its overall function as a transcriptional regular?

Hypoxia inducible factor; regulates genes that promote cell survival under ischemic conditions


HIF-1 is a crucial regulator of ______, which synchronizes cell responses, Hgb, and iron metabolism and other metabolic pathways, assuring ________ to satisfy body needs

erythropoietesis, red cell production


____ is a protein hormone produced by the ___ which binds receptors in the _____ where it stimulates production of RBC's

EPO, kidney, bone marrow


EPO is used to treat certain forms of anemia such as those due to _____

chronic kidney failure


Since EPO accelerates erythrocyte production is also increases ____

CaO2 (O2 carrying capacity)


What is blood doping and how is it accomplished?

Artificially increasing RBC to improve athletic performance, previous was accomplished via transfusion and now via EPO injection


How is blood doping dangerous?

increases blood viscosity [blood can sludge and clog capillaries leading to stroke or heart attack] and xs prolif of RBC's can cause polycythemia


Why is blood doping so difficult to detect?

Recombinant EPO is identical to endogenous. Can be differentiated by HCT, retic count, soluble transferrin receptor content and concn of b-globin mRNA.


What is the rate limiting step of hepatic heme synthesis and where does it occur?

FIRST STEP - delta-aminolevulinate synthase (delta-ALA synthase) catalyzed step, occurs in mitochondria


ALAS-N synthesis is inhibited by _____ and induced by _____

heme, compounds that increase hepatic cytochrome P450 synthesis (needs heme)


What variant of ALAS is found in the liver and which is found in erythroid cells?

ALAS-N in liver (ALAS non-specific or ALAS-1); ALAS-2 found in erythroid cells


True/False: Like ALAS-1 in liver cells, ALAS-2 in erythroid cells is limited by heme

FALSE - heme does not repress ALAS-2 expression in erythroid cells - thus regulation is different in erythroid cells than liver


Describe heme catabolism. What is the rate limiting step?

heme --> biliverdin --> bilirubin
Heme converted to biliverdin via heme oxygenase (RLS)
Biliverdin converted to bilirubin via biliverdin reductase


Heme is converted to bilirubin by _______

reticuloendothelial cells


How does bruising exemplify heme catabolism?

Purple color of heme in hematoma (bruise) converted to yellow pigment of bilirubin


Bilirubin is transported to the _____ bound to plasma _____ where the majority of further metabolism occurs

liver, albumin


In the liver's ______, bilirubin uptake occurs then bilirubin is conjugated to ______ and secreted in _____

parenchymal cells, glucuronate, bile


Bilirubin is readily excreted in bile as soluble form ________ and then further reactions occur via bacteria in the ____

bilirubin diglucorinide, colon


Hyperbilirubinemia causes _____



What three situations could cause hyperbilirubinemia?

damaged liver that cannot excrete normal amount of bilirubin; overproduction of bilirubin; obstruction of excretory ducts of liver


_____ or ____ bilirubin is transported to liver where it is ______ to ______

indirect, unconjugated (UN-IN), conjugated, direct


What would cause an increase in unconjugated bilirubin vs conjugated bilirubin?

unconjugated - overproduction, impaired uptake, impaired conjugation

conjugated - decreased excretion into the bile ductules or backward leakage


What is the most common cause of unconjugated hyperbilirubinemia? What are the dangers and how is it treated?

Physiologic jaundice - common in babies due to immature hepatic system that cannot conjugate bilirubin (bilirubin-UGT activity reduced --> reduced synth of UDP-glucoronic acid)
Dangers - unconjugated bilirubin can penetrate blood brain barrier --> toxic encephalopathy (kernicterus) or mental retardation
TX - blue light (phototherapy) - promotes hepatic excretion of unconjugated bili by converting it into other derivatives that are excreted in bile


True/False- O2 sensing mechanism is present in all cells



What coordinates regulation of O2 transport?

erythropoiesis and iron metabolism


True/False: Iron has very low bioavailability because most commonly forms are iron-oxide and metallic iron which have little use to organisms



Oxygen is normally in a _____ state meaning it has _______. Oxygen can react with iron in one electron _______

triplet, unpaired electrons, red ox reactions


Iron can easily be _____ and _____ from Fe2+ to Fe3+

oxidized and reduced


Iron plays a role in oxygen ____ and _____ via ______ and _______

transport, storage, Hgb, methoglobin


_______ in the electron transport chain contain both heme and iron-sulfer centers



_____ involved in amino acid metabolism and ______ used in the inflammatory response both contain iron

monooxygenases, dioxygenases


Iron and O2 generate ______ and there are many mechanisms in place to avoid production of _____

free radicals; xs reactive oxygen metabolites


_____, ______, and ______ sequester iron and change environment of iron to avoid unwanted side effects

binding proteins, protoporhyrins, and Fe-S centers


How does iron and oxygen generate free radicals?

Iron gives up an electron to oxygen --> Fe3+ and superoxide anion (O2-)


____ is the iron from meat, wherea's ______ is the iron found in mother's milk

heme, lactoferrin


Where in the body is iron absorbed?

upper small intestine


Total body content of iron is ______ and system usually has enough due to reclamation by _______

3-5 grams, reticuloendothelial system


True/False: Function of the diet is to keep iron concentration of the body topped off



How can excessive needs of iron be met by the body?

depletion of Fe-ferritin stores and increased iron uptake


About 1mg of iron is lost per day. What are the 4 main mechanisms by which iron is lost?

through intestine (occult blood loss), sloughed enterocytes, biliary secretions, skin cells

[also menstruation, blood donation, hemorrhage (nosebleeds), pregnancy]


Heme-iron is taken up by a heme transporter (HT) protein and once in cell _______ splits iron from heme

heme dioxygenase


True/False: Gut environment promotes Fe2+ to Fe3+



Fe3+ is reduced to Fe2+ by _______ at ______

ferric reductace, duodenal cytochrome b


After reduction, Fe2+ is transported by ___ across ____ of the enterocyte, into the enterocyte

DMT1, apical


Once in the enterocyte, _______ aided by hephaestin transports Fe2+ to interstitial fluid then to plasma. In the process, hephaestin converts Fe2+ to ____

ferroportin (fp), Fe3+


After entering the plasma, plasma Fe3+ binds to ______ to form ______

apo-transferrin, transferrin


True/False: SOme Fe2+ is stored as Fe3+-ferritin in enterocyte



______ is the major storage protein of iron and contains _____ per protein molecule in the form of Fe3+ oxide-hydroxide

ferritin, 4500 irons


What is the aggregated form of Fe3+ oxide-hydroxide (ferritin storage molecule) called? This is seen in iron overload

hemosiderin (partially degraded)


True/False: Serum ferritin level is the most convenient lab test to estimate iron stores



Why is transferrin used as a carrier of iron in plasma?

Fe(III) is insoluble at physiological pH so transferrin needed to bind iron(III) to avoid precipitation in plasma


True/False: Essentially all plasma iron is bound to transferrin because free iron is damaging at high concentrations

FALSE - free iron is damaging even at low concentrations


Transferrin carries ___ Fe3+ atoms at a time and the % saturation of transferrin with iron usually around ___

2, 33%


There are about _____ transferrin receptors on the cell surface of a developing erythroblast



Transferrin binding to receptor is modulated by _____



Once transferrin binds to transferrin receptor, the entire complex is endocytosed. The interior of the endosome is then acidified to release _____ via ferric reductase which is then taken up by the mitochondria and used by ______ to load iron into heme

Fe2+, ferrochetolase


After losing its Fe in the endosomal vesicle, what happens to transferrin?

apotransferrin is recycled back to the plasma to bind more Fe3+


True/False: transferrin receptors return to the membrane after being endocytosed



What is the job of the iron regulatory proteins?

stabilize transferrin receptor mRNA


The _____ is the primary site of iron storage and is the master control organ.



______ is a peptide produced by the liver to inhibit processes that put iron into blood and may be a master regulator of iron homeostasis.



How does hepcidin inhibit liver processes ?

When hepicidin concentration is high, hepcidin directly interacts with ferroportin and causes its internalization, therefore trapping iron in enterocytes, macrophages and hepatocytes


What two conditions stimulate hepcidin production?

inflammation and iron overload


True/False: Even at low concentrations, hepicidin significantly inhibits iron from entering the plasma

FALSE - at low concentrations, iron enters plasma at high rate


In duodenal epithelial cells (AKA villus), dietary iron imported via _____. Enters plasma via _____ that is regulated by ______.

DMT1, ferroportin, hephaestin


In liver parenchymal cells, iron imported via _____ and enters plasma via _______ that is regulated by ____.

transferrin receptor, ferroportin, ceraluplasmin


In reticuloendothelial macrophages (which recycle iron), iron imported via ____ and enters plasma via _____ which is regulated by _____

phagocytosis of RBC, ferroportin, ceraluplasmin


Iron imported into RBC precursors via ______ and then enters plasma via ____

transferrin receptor; being in an RBC that is eventually phagocytosed [TRICK QUESTION]


Iron transported into an RBC precursor is converted to a Hb-heme complex via _____

mitochondrial ferrochetolase


Which of the following do not contain a ferroportin protein for iron export in their membrane?
a) liver parenchymal cell
b) RBC precursor
c) reticuloendothelial macrophages
d) duodenal epithelial cells



How does iron regulate expression of FE-binding proteins such as ferritin? [think IRE and IRP]

The ferritin coding sequence mRNA has an iron response element (IRE) on its 5' end. At low iron concentration, the IRE is bound by iron regulatory proteins and IRP has a 3Fe-4S sulfur center. In this configuration, translation of iron is blocked. When iron levels are high, iron will bind to IRP and convert iron sulfur center to a 4Fe-4S center. This changes the conformation so IRP no longer binds tightly to IRE on 5' end. WHen there is no IRP bound, translation proceeds and you will get high ferritin synthesis.


Why is ferritin not needed when iron is low?

because ferritin is a storing protein, so if iron is low, won't need to store as much


In _______, there is an inappropriate increase in _____ iron absorption which results in deposition of excessive amount of iron in _____ with eventual tissue damage and impaired function of organs

hemochromatosis, intestinal, parencyhmal cells


When xs iron is deposited in parenchymal cells, it is deposited in the form of ______

hemsodiren (aggregated ferritin)


What are the 3 primary affected tissues in hematochromatosis?

liver-cirrhosis, pancreas-diabetes, skin-bronze (bronze diabetes)


The primary cause of hemochromatosis is a ______ allele that contains a _____ gene that associates with beta-2-microglobulin and forms complex with transferrin receptor

autosomal recessive, MHC1


True/False: The genetic form of hematochromatosis is the primary cause of iron overload.



How is the overload in hemochromatosis reflected and when?

serum ferritin concentrations, start to increase in later teens [increase in ferritin parallels the severity of the disease]


True/False: Serum ferritin contains little or no iron



True/False: Tissue concentrations of ferritin are much higher



What is the most common cause of poisoning deaths in children less than 6 years old?

acute accidental iron poisoning [most often vitamins]


What is the treatment for acute iron poisoning?

strong laxative and IV deferoxamine mesylate


How does IV deferoxamine mesylate (desferal) treat iron poisoning?

binds iron and excreted in urine


Why is iron poisoning toxic?

Serum free iron is not bound to transferrin and is highly toxic because it can cause lipid peroxidation which damages blood vessels (changing BP) and damage mitochondrial membranes (causing problems with O2 handling)


What is the most common amount of anemia?

iron deficiency


True/False: iron deficiency results from blood loss in most adults



True/False: about 5% of premenopausal women are iron deficiency anemic



What are three characteristics of iron deficiency anemia?

weakness, pallor, exercise intolerance


What is the amount of blood in the body of an average adult? During donation, how much iron is lost?

10 pints; 200-250mg


Donating one unit (equal to one pint) of blood per year is equivalent to an increased requirement for iron of _____ per day

0.65 mg


True/False: If males donated one unit per year, that would halve the serum ferritin level



True/False: Males can donate 2-3 times per year without appreciable incidence of iron deficiency, and women can only donate about half that amount, which makes them more susceptible



The first step of the heme synthesis pathway involves _____ and ______

succinyl CoA, glycine


2) after d-ALA is formed, two molecules are dehydrated via ______ to form _______, a pyrrole precursor

ALA dehyrase, porphobilinogen


3) Porphobilinogen is then catalyzed by uropophyrinogen ____ and ____ synthase in subsequent steps to yield ________, and in the process lose ___

I, III, uroporyphyrinogen III (that was a gimme), 4 ammonium ions


4) The uroporphyrinogen III contains ____ and _____ sidegroups that are important in helping the heme insert into the hydrophobic cleft of the ______

acetate, proprionyl


5) Uroporphyrinogen III is then converted to _____ via uroporphyrinogen decarboxylase in a reaction that loses _____. In this process, the acetate side groups are converted to _____

coproporphyrinogen III, 4 CO2, methyl


6) Coproporphyrinogen III is then converted to _______ via coproporphyrinogen oxidase in a process that loses _____. In this process, some of the proprionyl side groups are converted to _____

protoporyphyrinogen IX, 2 CO2, vinyl


7) The protoporphyrinogen IX molecule is then converted to ________ via protoporphyrinogen oxidase. What other major change takes place?

protoporphyrin IX. Double bonds are added to the rings so the molecule becomes red in color [previously colorless]


8) Protoporphyrin IX then reacts to form heme via _____. ____ is coordinated to the pyrrole nitrogens when added into the ring.

ferrochetolase, Fe2+


Which enzymes involved in the heme synthesis pathway are found in the cytosol? Which are found in the mitochondria?

1, 6, 7, 8 [ALA-synthase, coprop oxidase, photopor oxidase, ferrochetalase] are in the cytosol

The rest are found in the mitochondria


True/False: The heme biosynthesis pathway begins in the cytosol and ends in the mitochondria

FALSE: begins in mito, then in cytoplasm, begin in mito


Individuals with low activities of ALA-synthase (enzyme 1) develop ______



_____ are genetic or acquired abnormalities in heme synthesis pathway that develop due to depression of enzyme ____ activity

porphyria, 3-8


Mutations in DNA leading to accumulation of ALA and PBG (first two steps) and/or decrease in heme in cells and body fluids would lead to what symptoms?

neuropsychiatric signs and symptoms


Mutations in DNA leading to accumulation of porphyrinogens in skins and tissues would lead to what symptoms? How?

Photosensitivity. Porphyrinogens would spontaneously oxidase to porphyrins in the light. This causes lesions and discomfort.