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B2 > Pulmonary Biochemistry Week 3 > Flashcards

Pulmonary Biochemistry Week 3 Flashcards

1
Q

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

A

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

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2
Q

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 ______

A

pH, [HCO3-], PaCO2

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3
Q

Davenport diagrams reflect the presence of _______ buffers in the blood

A

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

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4
Q

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

A

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]

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5
Q

Describe three non-pulmonary causes of acute respiratory acidosis

A

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

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6
Q

Name 5 pulmonary causes of acute respiratory acidosis

A

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

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7
Q

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

A

PaCO2, [HCO3-]

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8
Q

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

A

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

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9
Q

______ is caused by an increase in central drive to breathe

A

Respiratory alkalosis

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10
Q

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

A

True

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11
Q

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

A

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

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12
Q

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

A

True

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13
Q

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

A

Stimulation of sense receptors; anxiety (psych); hypoxemia

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14
Q

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

A

stimulation of sense receptors; pain (psych); hypoxemia

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15
Q

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

A

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

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16
Q

How does hypoxemia cause respiratory alkalosis?

A

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

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17
Q

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

A

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]

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18
Q

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

A

hepatopulmonary syndrome, hypoxemic

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19
Q

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

A

hypercapnia, alveolar hypovenilation, hypocapnia, alveolar hyperventilation

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20
Q

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-

A

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

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21
Q

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-

A

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.

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22
Q

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

A

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]

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23
Q

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

A

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.

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24
Q

Metabolic acidosis is caused by an imbalance between _______ and ______

A

organic acid production, consumption

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25
Q

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?

A

Oxygen

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26
Q

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

A

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)

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27
Q

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

A

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

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28
Q

How does vomiting or nasogastric drainage cause metabolic alkalosis?

A

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

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29
Q

What two mechanisms are required for metabolic alkalosis to occur?

A

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

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30
Q

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

A

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

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31
Q

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

A

volume depletion, hypokalemia, aldosterone excess

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32
Q

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

A

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.

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33
Q

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

A

True

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34
Q

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

A

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

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35
Q

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

A

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

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36
Q

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?

A

Yes

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37
Q

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

A

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

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38
Q

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

A

TRUE

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39
Q

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

A

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

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40
Q

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

A

4 days; 8 days [highly variable]

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41
Q

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

A

10 minutes

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42
Q

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

A

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

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43
Q

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?

A

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.

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44
Q

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?

A

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].

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45
Q

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

A

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

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46
Q

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

A

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

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47
Q

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

A

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

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48
Q

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

A

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

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49
Q

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

A

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

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50
Q

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

A

mixed

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51
Q

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

A

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-

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52
Q

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

A

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

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53
Q

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

A

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

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54
Q

What is the anion gap? [think equation]

A

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

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55
Q

How is total venous CO2 measured with arterial blood gas?

A

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

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56
Q

How is total venous CO2 measured with venous electrolytes?

A

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-]

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57
Q

Venous CO2 is ______ than arterial [HCO3-]

A

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

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58
Q

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

A

sulfate, phosphate, organic anions, protein

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59
Q

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

A

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

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60
Q

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?

A

non-gap acidosis

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61
Q

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

A

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

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62
Q

_____ and _____ are the predominant anions in ketoacidosis

A

acetoacetate, beta hydroxybutyrate

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63
Q

______ is the predominant anion in lactic acidosis

A

lactate

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64
Q

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

A

renal failure [normal excreted by the kidney]

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65
Q

_______ is a product of anaerobic metabolic and increased with ______

A

lactic acid; hypoxia

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66
Q

what are the two most common causes of lactic acidosis?

A

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

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67
Q

What three conditions would be produce an overproduction of ketoacids?

A

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

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68
Q

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

A

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

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69
Q

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

A

FALSE - diarrhea

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70
Q

What are the two sites of heme biosynthesis?

A

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

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71
Q

True/False: heme and iron metabolism are tightly coupled

A

TRUE DAT

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72
Q

Heme is composed of ____ and _____

A

Fe2+, protoporphyrin IX

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73
Q

Hypoxia stimulates eryhthropoiesis which requires ____, ____ and _____

A

iron, Hb, heme

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74
Q

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

A

erythroid progenitors, erythroblasts

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75
Q

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

A

expulsion of the nucleus, reticulocyte

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76
Q

What organelles do reticulocytes lose? [nucleus already lost]

A

mitochondria, ribosomes

77
Q

Mature erythrocytes participate in what 3 metabolism processes?

A

glycolysis, pentose phosphate shunt, reductive capacity

78
Q

Describe how hypoxia and normoxia affects HIF-1 postranslational regulation

A

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

79
Q

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

A

prolyl hydroxylase

80
Q

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

A

EPO, transferrin, transferrin receptor, ceruloplasmin

81
Q

______ is involved in iron uptake

A

transferrin receptor

82
Q

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

A

ceruloplasmin

83
Q

_____ is involved in iron transport

A

transferrin

84
Q

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

A

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

85
Q

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

A

erythropoietesis, red cell production

86
Q

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

A

EPO, kidney, bone marrow

87
Q

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

A

chronic kidney failure

88
Q

Since EPO accelerates erythrocyte production is also increases ____

A

CaO2 (O2 carrying capacity)

89
Q

What is blood doping and how is it accomplished?

A

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

90
Q

How is blood doping dangerous?

A

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

91
Q

Why is blood doping so difficult to detect?

A

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

92
Q

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

A

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

93
Q

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

A

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

94
Q

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

A

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

95
Q

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

A

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

96
Q

Describe heme catabolism. What is the rate limiting step?

A

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

97
Q

Heme is converted to bilirubin by _______

A

reticuloendothelial cells

98
Q

How does bruising exemplify heme catabolism?

A

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

99
Q

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

A

liver, albumin

100
Q

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

A

parenchymal cells, glucuronate, bile

101
Q

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

A

bilirubin diglucorinide, colon

102
Q

Hyperbilirubinemia causes _____

A

jaundice

103
Q

What three situations could cause hyperbilirubinemia?

A

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

104
Q

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

A

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

105
Q

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

A

unconjugated - overproduction, impaired uptake, impaired conjugation

conjugated - decreased excretion into the bile ductules or backward leakage

106
Q

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

A

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

107
Q

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

A

True

108
Q

What coordinates regulation of O2 transport?

A

erythropoiesis and iron metabolism

109
Q

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

A

True

110
Q

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

A

triplet, unpaired electrons, red ox reactions

111
Q

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

A

oxidized and reduced

112
Q

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

A

transport, storage, Hgb, methoglobin

113
Q

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

A

cytochromes

114
Q

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

A

monooxygenases, dioxygenases

115
Q

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

A

free radicals; xs reactive oxygen metabolites

116
Q

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

A

binding proteins, protoporhyrins, and Fe-S centers

117
Q

How does iron and oxygen generate free radicals?

A

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

118
Q

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

A

heme, lactoferrin

119
Q

Where in the body is iron absorbed?

A

upper small intestine

120
Q

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

A

3-5 grams, reticuloendothelial system

121
Q

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

A

True

122
Q

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

A

depletion of Fe-ferritin stores and increased iron uptake

123
Q

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

A

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

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

124
Q

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

A

heme dioxygenase

125
Q

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

A

True

126
Q

Fe3+ is reduced to Fe2+ by _______ at ______

A

ferric reductace, duodenal cytochrome b

127
Q

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

A

DMT1, apical

128
Q

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

A

ferroportin (fp), Fe3+

129
Q

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

A

apo-transferrin, transferrin

130
Q

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

A

True

131
Q

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

A

ferritin, 4500 irons

132
Q

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

A

hemosiderin (partially degraded)

133
Q

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

A

True

134
Q

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

A

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

135
Q

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

A

FALSE - free iron is damaging even at low concentrations

136
Q

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

A

2, 33%

137
Q

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

A

300K-400K

138
Q

Transferrin binding to receptor is modulated by _____

A

HFE

139
Q

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

A

Fe2+, ferrochetolase

140
Q

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

A

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

141
Q

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

A

true

142
Q

What is the job of the iron regulatory proteins?

A

stabilize transferrin receptor mRNA

143
Q

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

A

Liver

144
Q

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

A

Hepcidin

145
Q

How does hepcidin inhibit liver processes ?

A

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

146
Q

What two conditions stimulate hepcidin production?

A

inflammation and iron overload

147
Q

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

A

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

148
Q

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

A

DMT1, ferroportin, hephaestin

149
Q

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

A

transferrin receptor, ferroportin, ceraluplasmin

150
Q

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

A

phagocytosis of RBC, ferroportin, ceraluplasmin

151
Q

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

A

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

152
Q

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

A

mitochondrial ferrochetolase

153
Q

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

A

B

154
Q

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

A

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.

155
Q

Why is ferritin not needed when iron is low?

A

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

156
Q

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

A

hemochromatosis, intestinal, parencyhmal cells

157
Q

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

A

hemsodiren (aggregated ferritin)

158
Q

What are the 3 primary affected tissues in hematochromatosis?

A

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

159
Q

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

A

autosomal recessive, MHC1

160
Q

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

A

True

161
Q

How is the overload in hemochromatosis reflected and when?

A

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

162
Q

True/False: Serum ferritin contains little or no iron

A

FALSE

163
Q

True/False: Tissue concentrations of ferritin are much higher

A

true

164
Q

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

A

acute accidental iron poisoning [most often vitamins]

165
Q

What is the treatment for acute iron poisoning?

A

strong laxative and IV deferoxamine mesylate

166
Q

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

A

binds iron and excreted in urine

167
Q

Why is iron poisoning toxic?

A

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)

168
Q

What is the most common amount of anemia?

A

iron deficiency

169
Q

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

A

True

170
Q

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

A

True

171
Q

What are three characteristics of iron deficiency anemia?

A

weakness, pallor, exercise intolerance

172
Q

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

A

10 pints; 200-250mg

173
Q

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

A

0.65 mg

174
Q

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

A

True

175
Q

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

A

True

176
Q

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

A

succinyl CoA, glycine

177
Q

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

A

ALA dehyrase, porphobilinogen

178
Q

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

A

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

179
Q

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

A

acetate, proprionyl

180
Q

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 _____

A

coproporphyrinogen III, 4 CO2, methyl

181
Q

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 _____

A

protoporyphyrinogen IX, 2 CO2, vinyl

182
Q

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

A

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

183
Q

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

A

ferrochetolase, Fe2+

184
Q

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

A

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

The rest are found in the mitochondria

185
Q

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

A

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

186
Q

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

A

anemia

187
Q

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

A

porphyria, 3-8

188
Q

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?

A

neuropsychiatric signs and symptoms

189
Q

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

A

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

B2 (15 decks)

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