Hemoglobinopathies and Porphyrins Flashcards
0
Q
Components of hemoglobin
A
1 Protein
2 Globin (2 pairs of polypeptide chains)
3 4 heme molecules
1
Q
Oxygen carrying pigment of blood
A
Hemoglobin
2
Q
Polypeptide
A
Binds one heme molecule
3
Q
Heme
A
Consists of protoporphyrin IXa linked to an iron II ion to which oxygen becomes reversibly bound during oxygen transport
4
Q
Hemoglobin F
A
Alpha, gamma
5
Q
Hemoglobin A
A
Alpha, beta
6
Q
Hemoglobin A2
A
Alpha, delta
7
Q
Hemoglobin H
A
Beta
8
Q
Hemoglobin Bart’s
A
Gamma
9
Q
Hemoglobinopathies
A
Genetically determined abnormalities of protein synthesis
10
Q
Qualitative hemoglobinopathies
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Involve amino acid substitutions
11
Q
Quantitative hemoglobinopathies
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Involve defects in rate of synthesis
12
Q
Effects of qualitative hemoglobinopathies
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1 Clinically silent
2 Hemoglobin solubility
3 Hemoglobin stability
4 Oxygen carrying capacity
13
Q
Symptoms of amino acid substitution
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1 Pallor
2 Hypoxia
3 Cyanosis
4 Dizziness
14
Q
Abnormal derivatives of hemoglobin
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1 Methemoglobin
2 Sulfhemoglobin
3 Carboxyhemoglobin
15
Q
Thalassemias
A
Inherited defects in the rate of synthesis of one of the globin chains
16
Q
Consequences of thalassemia
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1 Ineffective erythropoiesis
2 Hemolysis
3 Anemia
17
Q
Congenital methemoglobinemia
A
Cyanosis
18
Q
Sulfhemoglobin
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1 Poorly characterized derivatives of hemoglobin
2 Incapable of carrying oxygen
19
Q
Oxidized hemoglobin with iron in the ferric form
A
Methemoglobin
20
Q
Result to methemoglobin
A
1 Normally produced in RBCs
2 Inherited deficiency of reductase enzyme
3 Ingestion of large amounts of drugs (e.g. Sulfonamides)
21
Q
Brown color to plasma
A
Methemalbumin
22
Q
Brown color to urine
A
Free methemoglobin
23
Q
Results of toxic methemoglobinemia
A
1 Anemia
2 Vascular collapse
3 Death
24
The affinity of hemoglobin for this gas is approximately 200x greater than for oxygen
Carbon monoxide
25
Carboxyhemoglobin
Formed from hemoglobin in the presence of carbon monoxide
26
T or F. Only a small amount of carbon monoxide is needed to reduce oxygen carrying capacity of blood
T
27
Effect of carboxyhemoglobin in oxyhemoglobin dissociation curve
Left shift decreasing availability of oxygen to tissues
28
Oxyhemoglobin dissociation curve
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1 Left shift
Increased affinity
Decreased temperature
Decreased 2-3 DPG
Decreased [H+]
CO
2 Right shift
Reduced affinity
Increased temperature
Increased 2-3 DPG
Increased [H+]
```
29
Porphyrias
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1 Gamma-Aminolevulinic acid dehydratase porphyria
2 Acute intermittent porphyria
3 Congenital erythropoietic porphyria
4 Porphyria cutanea tarda
5 Hereditary coproporphyria
6 Variegate porphyria
7 Erythropoietic protoporphyria
```
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Reduce heme molecule
Porphyrins
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Causes accumulation of ALA synthase
Deficiency in one of the enzymes
32
Major sites of porphyrin synthesis
1 Liver
| 2 Erythroid bone marrow
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Characteristics of porphyrins
1 Dark red in color
| 2 Intensely fluorescent
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Porphyrins
Product of excreted porphyrinogens (oxidized)that are unstable in the feces or urine
35
Results in formation of excessive quantities of porphyrin precursors or porphyrins
Partial deficiency of one of the enzymes of porphyrin synthesis leading to decreased formation of heme --> ALA synthase from inhibition
36
Autosomal dominant disease that results from defects in the enzyme porphobilinogen deaminase
Acute intermittent porphyria
37
Predominant problem of acute intermittent porphyria
Neurologic damage (that leads to peripheral and autonomic neuropathies and psychiatric manifestations)
38
Inducers of porphyria
Chemicals or situations that boost heme synthesis (i.e. Fasting and medications)
39
Sequence of events in attacks caused by acute intermittent porphyria
1 Abdominal pain
2 Psychiatric symptoms such as hysteria
3 Peripheral neuropathies, mainly motor neuropathies
40
Associated with porphyria
Drugs that lead to increased activity of the hepatic P450 system (i.e. Phenobarbital, sulfonamides, estrogens, alcohol)
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Biologically useless but cause cutaneous photosensitivity characterized by blisters, erosions, and scarring of light exposed skin
Porphyrins of the isomer I type
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Congenital erythropoietic porphyria
Inheritance of 2 mutant alleles for the gene encoding the enzyme uroporphyrinogen III synthase leading to accumulation of porphyrins of the isomer I type
43
Causes mutilation
Chronic damage of skin, cartilage, and bones
44
Signs and symptoms of congenital erythropoietic porphyria
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1 Hypertrichosis
2 Erythrodontia
3 Reddish-colored urine
4 Hemolytic anemia
5 Splenomegaly
6 Osseos fragility
```
45
Porphyria cutanea tarda
Group of acquired and familial disorders in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient
46
Cause of manifestations of porphyria cutanea tarda
Increased mechanical fragility after sunlight exposure
47
Erosions and blisters form painful indolent sores that heal with milia, dyspigmentation, and scarring
Porphyria cutanea tarda
48
Contributory factors of porphyria cutanea tarda
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1 Ethanol intake
2 Estrogen therapies
3 Hemochromatosis genes
4 Hepatitis
5 Human immunodeficiency viral infections
```
49
Requirement of clinical expression of both sporadic and familial porphyria cutanea tarda
1 Exposure to environmental or infectious agents
| 2 Presence of existing conditions that adversely affect hepatocytes
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Other common features of porphyria cutanea tarda
1 Hypertrichosis
2 Sclerodermalike plaques that may develop dystrophic calcification
3 Excretion of discolored urine caused by porphyrin pigments
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Porphyria that causes urine that resembles port wine or tea
Porphyria cutanea tarda
52
Total iron content of the adult body
Approximately 4 g (2/3 in hemoglobin)
53
Contain 1/4 of the body's iron
Iron stores (spleen, liver, bone marrow)
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T or F. Most of the remainder of iron is in myoglobin and other hemoproteins
T
55
0.1% iron
In plasma where it is bound to transferrin
56
Main site of iron absorption
Small bowel
57
Readily absorbed iron
Ferrous iron
58
Dietary iron
Ferric iron
59
Important in iron absorption
Gastric secretions
60
Mean daily intake of iron
About 20 mg but less than 10% is absorbed
61
Facilitate iron absorption
1 Ascorbic acid
| 2 Reducing substances
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Decrease absorption of iron
1 Phytic acid
2 Phosphates
3 Oxalates
63
Iron absorption and transport
1 Iron is absorbed in intestinal mucosal cells
2 Iron is transported directly into the bloodstream or combines with apoferritin to form ferritin
3 In the blood, iron is transported mainly bound to transferrin. Transferrin is normally 1/3 saturated with iron
4 Iron is lost from the body in feces, desquamation of skin, and menstrual blood loss
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No physiologic excretion mechanism
Iron
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Transferrin: 75% of iron
Hemoglobin/erythropoiesis
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Transferrin: 10-20% of iron
Ferritin (stores iron in liver and heart)
67
Transferrin: 5-15% of iron
Other processes
68
Diagnostic tests for iron status
1 Plasma iron
2 Plasma total iron binding capacity
3 Plasma ferritin
69
Associated with low plasma concentrations
1 Infection
2 Trauma
3 Chronic inflammatory disorders
4 Neoplasia
70
Late feature of iron deficiency
Decreased levels of plasma iron
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Plasma iron
Useful in diagnosis of hemochromatosis
72
Functional measurement of transferrin concentration
Plasma total iron binding capacity
73
Normal value of transferrin saturation
33%
74
Transferrin saturation
Transferrin saturation = iron/TIBC x 100
75
Increases TIBC
Iron deficiency
76
Decreases transferrin saturation
1 Iron deficiency
2 Pregnancy
3 Chronic disease
77
Consistently increased in iron overload
Transferrin saturation
78
Normal range of plasma ferritin
20-300 mcg/L
79
Plasma ferritin
1 Low: decrease in body iron stores
2 Normal value: acutely ill (acute phase protein and patients with iron deficiency)
3 Increased: hemochromatosis, liver disease, cancer
80
PBG deaminase
Acute intermittent porphyria
81
Coproporphyrinogen
Hereditary coproporphyria
82
Uroporphyrinogen I synthase
Congenital erythropoietic porphyria
83
UPG III synthase
Congenital erythropoietic porphyria
84
Protoporphyrinogen oxidase
Variegate porphyria
85
Uroporphyrinogen decarboxylase
Porphyria cutanea tarda
86
Clinical features of acute intermittent porphyria
Abdominal pain
| Psychiatric symptoms
87
Clinical features of congenital erythropoietic porphyria
1 Photosensitivity
2 Red urine, teeth
3 Hemolysis
88
Clinical features of hereditary coproporphyria
Photosensitivity
89
Clinical features of variegate porphyria
Photosensitivity
90
Clinical features of porphyria cutanea tarda
Photosensitivity
91
Exacerbating factors of acute intermittent porphyria
Steroid hormones
92
Exacerbating factors of congenital erythropoietic porphyria
Sunlight
93
Exacerbating factors of hereditary coproporphyria
Stress
94
Exacerbating factors of variegate porphyria
Stress
95
Exacerbating factors of porphyria cutanea tarda
1 Alcohol
2 Hepatic injury
3 Iron overload
