Ch 5 Pathoma - RBC Disorders Flashcards
1
Q
Anemia is a reduction in ____.
A
RBC mass
2
Q
Name the 4 signs/symptoms of hypoxia
A
1) weakness, fatigue, dyspnea; 2) pale conjunctiva and skin; 3) headache and lightheadedness; 4) angina (especially with preexisting CAD - decrease O2 to heart)
3
Q
____, ____, and ____ are used as surrogates for RBC mass, which is difficult to measure
A
Hgb, hct, rbc count
4
Q
Anemia is defined as Hb less than ___ in males and less than ___ in females. Name the ranges.
A
13.5 g/dL; 12.5; 13.5-17.5; 12.5-16
5
Q
Name the ranges of MCV for microcytic, normocytic, and macrocytic anemias.
A
less than 80 80-100 more than 100
6
Q
Microcytic anemias are due to _____.
A
Decreased production of hemoglobin (microcytosis is due to an extra division which occurs to maintain hgb concentration)`
7
Q
Hemoglobin is made of ___ and ___, which is composed of ___ and ____. A decrease in any of these components may lead to ___ anemia.
A
globin and heme; iron and protoporphyrin; microcytic
8
Q
Name the 3 microcytic anemia (and the extra one pathoma thinks is one)
A
Iron deficiency anemia; sideroblastic anemia; thalassemia; anemia of chronic disease –> actually normocytic
9
Q
Iron deficiency leads to ___ heme, leads to ___ hemoglobin, leads to ___ anemia.
A
decreased; decreased; microcytic
10
Q
What is the most common nutritional deficiency in the world? It affect roughly 1/3 of world population
A
lack of iron
11
Q
Iron is consumed in ___ (meat derived) and ___ (vegetable derived) forms. Which one is more easily absorbed? Absorption occurs in the ___. Enterocytes have DMT1 transporters for both kinds.
A
heme; non-heme; heme; duodenum
12
Q
Enterocytes transport iron across the cell membrane into blood via ___. ___ transports iron in the blood and delivers it to ___ and ___ for storage. Stored intracellular iron is bound to ___, which prevents iron from forming free radicals via the ____.
A
ferroportin; transferrin; liver; bone marrow macrophages; ferritin; Fenton reaction (ferroportin in the enterocyte helps prevent us from absorbing iron in excess)
13
Q
What is total iron binding capacity (TIBC) a measure of?
A
A measure of transferrin molecules in the blood
14
Q
The lab for iron status, % saturation, measures the percentage of ___ molecules that are bound by iron (normal __%)
A
transferrin; 33
15
Q
Serum ___ reflects iron stores in macrophages and liver
A
ferritin
16
Q
Iron deficiency anemia is usually caused by ___ or ___. Name the main causes in infants, children, adults (male and female), and elderly (western world and developing)
A
dietary lack; blood loss; breast feeding (human milk is low in iron); poor diet; males: peptic ulcer disease, females: menorrhagia or pregnancy; WW: colon polyps/carcinoma; DVPW: hookworm (ancylostoma duodenal and necator americanus)
17
Q
Iron deficiency anemia can also be caused by gastrectomy. Why?
A
Gastrectomy can lead to decreased acid and acid aids iron absorption by maintaining the Fe2+ state, which more readily absorbed than Fe3+ (Fe2 goes in2 the body)
18
Q
In the first stage of iron deficiency, storage iron is depleted - H/N/L ferritin, H/N/L TIBC. When serum iron is depleted (stage 2), what lab tests do we see? Then what are the next two stages?
A
low ferritin (low stores); high TIBC (body is compensating for low iron); decreased serum iron and decreased saturation; normocytic anemia; microcytic, hypo chromic anemia
19
Q
Name 3 clinical features of iron deficiency. What is the treatment?
A
anemia, koilonychia (spoon shaped nails); pica (appetite or desire to chew on abnormal things like dirt or ice); supplemental iron
20
Q
Lab findings in iron deficiency anemia include: H/N/L RDW, ferritin, TIBC, serum iron, % saturation, free erythrocyte protoporphyrin (FEP)
A
high RDW, low ferritin, high TIBC, low serum iron, low % sat, high FEP
21
Q
_____ syndrome is iron deficiency anemia with esophageal web and atrophic glossitis. How does it present?
A
Plummer-Vinson; anemia, dysphagia, and beefy-red tongue
22
Q
Anemia of chronic disease is anemia associated with chronic ___ (e.g. endocarditis or autoimmune conditions) or ___. It is the most common type of anemia in ___ patients.
A
inflammation; cancer; hospitalized
23
Q
Chronic disease results in production of acute phase reactants from the ___, including ___, which sequesters iron in these two ways.
A
liver; hepcidin; 1) limiting iron transfer from macrophages to erythroid precursors; 2) surpressing erythropoietin (EPO) production
(trying to prevent bacteria from accessing iron needed for their survival)
24
Q
What type of cell is seen? What type of stain was used?
A
Ringed sideroblasts; prussian blue stain
(if protoporhyrin is deficient, the iron laded mitochondria form a ring around the nucleus)
25
What type of anemia is seen in anemia of chronic disease? And what is the treatment?
Can be normocytic or microcytic (depends on severity of Fe deficiency); address the underlying cause - exogenous EPO is useful in some pts especially cancer pts
26
Lab findings for anemia of chronic disease: ferritin, TIBC, serum iron, % saturation, and free erythrocyte protoporphyrin
high ferritin (inability to use storage iron so it piles up), low TIBC, low serum iron, low % saturation; high FEP
27
Sideroblastic anemia is anemia due to \_\_\_\_\_. Lab findings: ferritin, TIBC, serum iron, % saturation
defective protoporphyrin synthesis; high ferritin (bone marrow macrophages are storing the leaked Fe), low TIBC, high serum iron, high % sat (iron overloaded state)
28
Protoporphyrin is synthesized via a series of rxns. Succinyl Coa --(\_\_\_\_)--\> aminolevulinic acid (ALA), using ___ as a cofactor. This is the ___ step.
aminolevulinic acid synthetase (ALAS); vit B6; rate limiting
29
This enzyme converts ALA to porphobilinogen, which eventually gets converted to ___ after additional reactions. That then is attached to iron by ____ enzyme to make heme. This final reaction occurs in the \_\_\_.
Aminolevulinic acid dehydratase (ALAD); ferrochelatase; mitochondria
30
When sideroblastic anemia is congenital, the defect most commonly invovles \_\_\_. Name the three acquired causes.
ALAS (rate limiting enzyme); alcoholism (which is a mitchondrial poison), lead poisoning (inhibits ALAD and ferrochelatse), vitamin B6 (required cofactor for ALAS; most commonly seen as side effect of isoniazid tx for TB)
31
Lead poisoning is an acquired cause of sideroblastic anemia that works by inhibiting ___ and \_\_\_. Vit B6 deficiency is another cause since it is a cofactor for \_\_\_. A vit B6 deficiency is most commonly seen as a side effect of \_\_\_\_.
ALAD; ferrochelatase; ALAS; isoniazid (TB tx)
32
What type of RBCs are seen here? In which disease do we see this?
Target cells; B-thalassemia
33
Reactive bone formation leads to ____ appearance on xray (seen here), and facial bones ("\_\_\_\_"). This is due to massive \_\_\_\_, seen in this disease.
crew cut; chipmunk facies; erythroid hyperplasia; B-thalassemia major
34
Thalassemia is anemia due to decreased ____ of ___ of hemoglobin. It causes macro/normo/microcytic anemia. It is an inherited mutation, and carriers are protected against ____ malaria. Divided into __ and __ thalassemia based on decreased production of ___ or ___ \_\_\_\_.
synthesis; globin chains; microcytic; plasmodium falciparum; alpha; beta; alpha; beta; globin chains
35
Name the globin chains in HbF, HbA, HbA2, HbH, HbBarts, HbS, HbC. Which one is lethal in utero?
a2g2; a2b2; a2d2; b4; g4; HbBarts (die from hydrops fetalis); a2bs2; a2bc2
36
A-thalassemia is usually due to gene \_\_\_. Beta thalassemia is usually due to gene \_\_\_. There are __ alpha genes present on chromosome \_\_\_. There are __ beta genes present on chromosome \_\_\_.
deletion; mutation; 4; 16; 2; 11
37
When one alpha gene is deleted in alpha thalassemia, the pt is \_\_\_\_. When two genes are deleted the patient has ___ with increased/decreased RBC count. When there are two genes deleted the deletions can be either ___ or \_\_\_.
asymptomatic (they have 3 working copies); mild anemia; increased; cis or trans
38
Cis deletions in alpha thalassemia occur on same/different chromosomes. Seen more commonly in \_\_\_\_. Trans deletions occur on same/different chromosomes. Occur more commonly in \_\_\_. Which one is associated with increased risk of severe thalassemia in offspring?
same; Asians; different; Africans (and African Americans); cis (stand the chance to pass on a chromosome with no alpha genes on it)
39
In an alpha-thalassemia patient with three alpha genes deleted, you get severe \_\_\_\_. Beta chains form tetramers and you get Hb\_\_ that damage RBCs. When four alpha genes are deleted, it is ___ in utero. You get Hb\_\_\_ formed by ___ tetramers. Both be seen on electrophoresis.
anemia; HbH (the fetus can survive, b/c HbF can compensate even though there is only one alpha gene); lethal (fetus dies from hydrops fetalis); HbBarts; gamma
40
What is this and when is it seen?
Hypersegmented neutrophil; seen in megaloblastic anemia (due folate or vit B12 deficiency)
41
B-thalassemia is usually due to gene \_\_\_\_. Seen in individuals of ___ and ___ descent. Normally we have __ beta genes located on chromosome \_\_. Mutations result in ___ (B0) or ___ (B+) production of the B globin chain. Name the mildest and most sever forms.
mutations; African; Mediterranean; 2; 11; absent; diminished; B-Thal minor (B/B+); B-Thal major (B0/B0)
42
B-thalassemia minor (\_\_\_) is the mildest form and is usually asymptomatic with a increased/decreased RBC count. What do you see on blood smear? What do you see on hgb electrophoresis?
B/B+; increased; microcytic, hypochromic RBCs and target cells; slighlty decreased HbA with **elevated HbA2** (5%, normal 2.5%) and HbF (2%, 1% normal)
43
B-thalassemia major (\_\_) is the most severe form of disease and presents with severe ___ a few months after birth, since high __ at birth is temporarily protective. Unpaired __ chains precipitate and damage RBC membrane resulting in ineffective ___ and extravascular \_\_\_\_.
B0/B0; anemia; HbF; alpha; erythropoiesis; hemolysis (removal of circulating RBCs by the spleen)
44
What is seen on blood smear and in electrophoresis in B-thalassemia major pts? What is tx and what can this tx put you at risk for?
microcytic, hypochromic RBCs with target cells and nucleated RBCs; HbA2 and HbF with little or no HbA; chronic transfusions; secondary hemochromatosis (Fe overload, since body has no way to remove excess Fe)
45
In B-thalassemia major, massive erythroid ___ ensues resulting in these three things.
hyperplasia; 1) expansion of hematopoiesis into the skull (reactive bone formation leads to crew cut appearance on xray) and facial bones (chipmunk facies); 2) extramedullary hematopoiesis with hepatosplenomegaly; 3) risk of aplastic crisis with parvovirus B19 infxn of erythroid precursors
(1 and 2 occur b/c body is producing lots of EPO due to deficient RBCs)
46
In what disorder do you have a risk of an aplastic crisis with parvovirus B19 infection of erythroid precursors?
B-thalassemia major
47
What is the most common cause of macrocytic anemia? What cells are effected?
Folate and vitamin B12 deficiency (folate is more common); macrocytic RBCs, hypersegmented neutrophils, megaloblastic change also seen in rapidly dividing (intestinal) epithelial cells
(it is macrocytic since there is one less division since the synthesis of DNA precursors has been messed with)
48
What are seen in this picture? What is this due to?
Spherocytes; hereditary spherocytosis is an inherited defect of RBC cytoskeleton membrane tethering proteins (note the loss of central pallor, and increased RDW and MCHC)
49
Aside from folate and B12 deficiency name 3 other causes of macrocytic anemia.
alcoholism, liver disease, drugs (eg 5-FU)
(in these there is no megaloblastic change and therefore no hypersegmented neutrophils)
50
Dietary folate is derived from ___ and absorbed in the \_\_\_. Dietary vit B12 is derived from ___ and absorbed in the \_\_\_. Which one takes months vs years to develop and why?
green veggies/some fruits; jejunum; animal-derived proteins; ileum; folate vs B12; body folate stores are minimal, while we have large hepatic stores of B12
51
Name 3 causes of folate deficiency and types of people we see it in.
poor diet (alcoholics/elderly); increased demand (pregnancy, cancer, hemolytic anemia); folate antagonists (methotrexate, which inhibits DHF reductase)
52
Clinical and lab findings for folate deficiency include: macro/normo/microcytic RBCs, ___ neutrophils, this clinical finding, H/N/L serum folate, H/N/L homocysteine (which carries increased risk for \_\_\_), and H/N/L methylmalonic acid.
macrocytic; hypersegmented (\>5 lobes); glossitis; low; high; thrombosis; normal (means B12 is fine)
53
\_\_ enzyme liberates vitB12 in the mouth, which is then bound by ___ (also from salivary gland) and carried through the stomach. In the duodenum, B12 is detached by ____ and then binds ___ (made by ___ cells). This complex is absorbed in the \_\_\_.
Amylase; R-binder; pancreatic proteases; intrinsic factor; gastric parietal; ileum
54
Name the 3 P's of parietal cells
1) proton pump cells; 2) pink (compared to chief cells which are blue when stained); 3) associated with pernicious anemia
55
\_\_\_\_ is the most common cause of vit B12 deficiency and is due to autoimmune destruction of ___ cells, leading to ___ deficiency, and subsequent B12 absorption problems.
Pernicious anemia; parietal cells (found in the **body** of stomach); intrinsic factor
56
Aside from pernicious anemia, name 3 other causes of vit B12 deficiency
pancreatic insufficiency (decreased pancreatic proteases needed to free up vit B12 from R-binder); damage to terminal ileum (Crohn's or Diphyllobothrium latum [fish tapeworm]); vegans (absolute dietary deficiency)
57
Name 2 clinical findings of vit B12 deficiency.
glossitis and subacute combined degerneration of spinal cord (has to do with increased methylmalonic acid impairing spinal cord myelinization)
58
Lab findings for B12 deficiency: macro/normo/microcytic RBCs, with __ neutrophils; H/N/L: serum vit B12; serum homocysteine; methylmalonic acid
macrocytic; hypersegmented; low; high; high (unlike folate deficiency)
59
What are the two reactions vit B12 is needed for?
1) homocysteine --\> methionine
2) methylmalonic acid --\> succinyl CoA (impt in fatty acid metabolism)
60
In vit B12 deficiency (CNS problem), you have increased ___ due to lack of conversion to \_\_\_\_. This increase results in \_\_\_\_, due to impaired myelinization of the spinal cord, resulting in poor proprioception and vibratory sensation (\_\_\_ part of spinal cord) and spastic paresis (\_\_\_ part of spinal cord)
methylmalonic acid; succinyl coA (impt in FA metabolism); subacute combined degeneration of the spinal cord; posterior column; lateral corticospinal tract)
61
Normocytic anemia is due to ___ or \_\_\_. ___ helps to distinguish btwn these two etiologies.
increased peripheral destruction; underproduction; reticulocyte count
62
What is this larger cell with bluish cytoplasm? And why does it have bluish cytoplasm?
reticulocyte; residual RNA
63
Normal reticulocyte count is \_\_%. RBC lifespan is __ days. Each day roughly \_\_% of RBCS are removed from circulation and replaced by reticulocytes. A properly functioning marrow responds to anemia with a \_\_% increase.
1-2; 120; 1-2; \>3%
64
Corrected reticulocyte count (aka RPI) is = \_\_\_\_. Greater than __ % indicates good marrow response and suggests \_\_\_\_. Less than that indicates poor marrow response and suggests \_\_\_\_.
RCxHct/45; 3; peripheral destruction; underproduction
65
Peripheral RBC destruction (aka \_\_\_\_) can be divided into ___ and \_\_. Both result in anemia with a good/poor marrow response.
hemolysis; extravascular; intravascular; good
66
Extravascular hemolysis involves RBC destruction by the ___ system (macrophages in these three places). When macrophages consume RBCs and break down hgb, globin is broken down into \_\_\_. Heme is broken down into \_\_, which gets recycled and \_\_, which is broken down further to \_\_\_.
reticuloendothelial; spleen, liver, and LNs (all outside of bv's); amino acids; iron; protoporphyrin; unconjugated bilirubin
67
Protoporphyrin is broken down into \_\_\_\_, which is bound to serum ___ and delivered to the ___ for conjugation and excretion into the \_\_\_.
unconjugated bilirubin; albumin; liver; bile
68
Name the 4 clinical findings in extravascular hemolysis.
anemia with splenomegaly (hypertrophy); jaundice (due to unconjugated bilirubin); increased risk of bilirubin gallstone (due to increased conjugated bilirubin in the bile); marrow hyperplasia (with corrected retic count greater than 3%)
69
Name the 4 clinical findings in intravascular hemolysis.
1) decreased serum haptoglobin (b/c its binding up free Hb to recycle it in spleen); 2) hemoglobinemia; 3) hemoglobinuria; 4) hemosiderinuria (renal tubular cells pick up some hb that is filtered into urine and break it down into iron, which accumulates as hemosiderin; when they eventually shed, you get this result)
70
Hereditary spherocytosis is a sporadic/inherited defect of RBC ____ proteins, most commonly involving these 3.
inherited; cytoskeleton-membrane tethering; ankyrin, spectrin or band 3
71
In hereditary spherocytosis, membrane __ are formed and lost over time redering the cells ___ instead of __ shaped. Spherocytes are less able to maneuver through ___ and are consumed by \_\_\_, causing anemia
blebs; round; disc; splenic sinusoids; splenic macrophages
72
Hereditary spherocytosis is a macro/normo/microcytic anemia with predominant ___ hemolysis, so clinical findings include \_\_\_, ___ due to \_\_\_, and increased risk for \_\_\_\_. You also see an inc risk of ___ with __ infxn of \_\_\_.
normocytic; extravascular; splenomegaly; jaundice; unconjugated bili; bilirubin gallstones; aplastic crisis; parvovirus B19; erythroid precursors
73
Lab findings for hereditary spherocytosis: gain/no change/loss of central pallor, H/N/L RDW, MCHC. How do you diagnose it? How do you tx it?
loss; high (blebbing different amounts creates different sizes); high (as cell shrinks, hgb gets more concentrated); Dx: osmotic fragility test; tx: splenectomy (anemia resolves but Howell-Jolly bodies persist)
74
What does the osmotic fragility test help diagnose and how does it work?
hereditary spherocytosis; you see increased spherocyte fragility in hypotonic solution (less extra membrane than normal RBC so will burst quicker)
75
What is this? What does it mean?
Howell-Jolly body (fragments of nuclear material in RBCs); indicates splenic absence or dysfunction (spleen would normally remove them)
76
Sickle cell anemia is an autosomal/x-linked dominant/recesive mutation in the __ chain of hemoglobin. A single amino acid change replaces ___ (hydrophilic) with ___ (hydrophobic). This gene is carried by \_\_% of peeps with african descent, due to protective role against \_\_\_.
autosomal recessive; B; glutamic acid; valine; 10; falciparum malaria
77
Sickle cell disease arises when one/two abnormal B genes are present, resulting in \>\_\_% of Hb\_\_ in RBCs. This Hgb, ___ when deoxygenated, which causes aggregation into \_\_\_-like structures resulting in sickle cells
two; 90; HbS; polymerizes (no covalent bond; therefore is reversible); needle
78
There is an increased risk of sickling in these 3 conditions. These two things protect against sickling.
hypoxemia, dehydration, acidosis; HbF (which is why it presents after first few months of life); hydroxyurea (which increases levels of HbF)
79
In sickle cell anemia, cells continuously __ and __ while passing through microciruclation resulting in \_\_\_. You predominantley see ___ hemolysis, in which the __ system removes damaged RBCs leading to anemia and these 2 things
sickle; de-sickle; RBC membrane damage; extravascular; reticuloendothelial; jaundice w/unconj bili, and increased risk for bilirubin gallstones
80
In sickle cell anemia you also see less predominantely, ___ hemolysis, when RBCs w/damaged membranes \_\_\_, leading to hemolysis with decreased ___ and ___ on blood smear.
intravascular; dehydrate; haptoglobin; target cells
81
Due to the anemia in sickle cell disease, you also see massive ___ which results in expansion of ___ into the ___ ('crewcut' appearance on xray) and ___ ('chipmunk facies'), and an increase in extra-medullary ___ with \_\_\_. You also have a risk of \_\_\_.
erythroid hyperplasia; hematopoiesis; skull; facial bones; hematopoiesis; hepatomegaly; aplastic crisis with parvovirus B19 infxn of erythroid precursors.
82
Extensive sickling lead to complications of vaso-occlusion. Name 5.
dactylitis; autosplenectomy; acute chest syndrome; pain crisis; renal papillary necrosis
83
Dactylitis (complication of sickle cell anemia), presents as swollen ___ and ___ due to vaso-occlusive infarcts in \_\_\_. Common presenting sign in \_\_\_.
hands; feet; bones; infants (6 mo or so after HbF goes away)
84
Name the 3 consequences of autosplenectomy (a shrunken fibrotic spleen due to vaso-occlusion seen in sickle cell)
1) inc risk of infxn with encapsulated organisms like strep pneumo and H flu (this is the most common cause of death in children --\> vaccinate by 5 yrs; 2) inc risk of salmonella osteomyelitis; 3) Howell-Jolly bodies on blood smear
85
What is the most common cause of death in sickle cell anemia children? Adults?
Infxn with encapsulated organism like strep pneumo or H flu; acute chest syndrome
86
Acute chest syndrome (sickle cell complication), vaso-occlusion in ___ microcirculation, presents with these 3 symptoms and is often precipitated by \_\_\_. It is the most common cause of death in adult/children.
pulmonary; chest pain, SOB, lung infiltrates; pneumonia; adult
87
Renal papillary necrosis (vaso-occlusive complication of sickle cell) results in gross ___ and \_\_\_.
hematuria; proteinuria
88
Sickle cell trait is generally symptomatic/asymptomatic with/without anemia. The RBCs are less than \_\_% HbS and do not sickle in vivo except in the \_\_\_, because of the extreme ___ and \_\_\_. This leads to microinfarctions leading to microscopic ___ and decreased ability to concentrate \_\_\_.
asymptomatic; without; 50; renal medulla; hypoxia; hypertonicity; hematuria; urine
89
Lab findings sickle cell disease vs trait: what is seen on blood smear? What are the results of the metabisulfite screen? How much HbS is seen on electrophoresis?
disease: sickle cells and target cells (neither in trait); metabisulfite is positive in both (it causes cells with any HbS to sickle); 90% HbS vs 43% HbS (disease: 8% HbF, 2% HbA2 and **NO** HbA; trait: 55% HbA, 2% HbA2)
90
People with hemoglobin C have an autosomal/x-linked dominant/recessive mutation in __ chain of hgb in which amino acid ___ is replaced by \_\_\_. It is more/less common than sickle cell disease. Presents with mild anemia due to ___ hemolysis. Characteristic HbC __ are seen in blood smear.
autosomal recessive; glutamic acid; lysine; less; extravascular; crystals
91
What is this?
Hemoglobin C crystal
92
Name 2 normocytic anemias with predominant extravascular hemolysis. Name 5 normocytic anemias with predominant intravascular hemolysis.
Hereditary spherocytosis, sickle cell anemia; Paroxysmal nocturnal hemoglobinuria (PNH), G6PD deficiency, Immune hemolytic anemia (IHA), Microangiopathic hemolytic anemia, Malaria
93
Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired/inherited defect in ___ resulting in absent \_\_\_, which renders cells susceptible to destruction by \_\_\_. Normally, ___ (anchoring glycolipid), secures ___ (CD55) on the surface of RBCs, which protects against complement mediated damage by inhibiting \_\_\_\_.
acquired; myeloid stem cells; glycosylphosphatidylinositol (GPI); complement; GPI; Decay accelerating factor (DAF); C3 convertase
94
In PNH, ___ hemolysis occurs often at night during sleep, due to mild respiratory acidosis/alkalosis, which develops with shallow breathing during sleep and activates \_\_\_. These 3 cell types are lysed, and the __ hemolysis leads to these 3 classic findings.
intravascular; acidosis; complement; RBCs, WBCs, and plts; intravascular; hemoglobinemia, hemoglobinuria (esp in morning), and hemosiderinuria (seen days after hemolysis)
95
\_\_\_ test is used to screen for PNH; the confimatory test is the ___ test or ___ to detect lack of CD\_\_ (DAF) on blood cells
Sucrose; acidified serum; flow cytometry; 55
(sucrose and acidified serum can both activate complement)
96
The main cause of death in PNH is ___ of the \_\_, \_\_, or \_\_\_. This is because destroyed \_\_\_, release their cytoplasmic contents into circulation, inducing \_\_\_.
thrombosis; hepatic, portal, or cerebral veins; platelets; thrombosis
97
Complications of PNH include ___ and \_\_\_, which develops in \_\_% of pts.
iron deficiency anemia (due to chronic loss of hgb in the urine); acute myeloid leukemia (AML); 10 (PNH is due to a myeloid stem cell mutation so one more would cause AML)
98
Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is an autosomal/x-linked dominant/recessive disorder resulting in reduced ___ of G6PD, which renders the cell susceptible to \_\_\_. What are the two a major variants and which one is more severe?
x-linked recessive; half-life; oxidative stress; African and Mediterranean (Med is more severe) - both protect against falciprum
99
RBCs are normally exposed to oxidative stress, in particular \_\_\_, which is neutralized by ___ (an antioxidant), but ___ is needed to regenerate it. G6PD helps with generating \_\_\_.
H2O2; glutathione (G-SH); NADPH (GS-SG --\> GSH); NADPH
100
In G6P deficiency, oxidative stress precipitates __ causing Heinz bodies, which are removed from RBCs by \_\_\_, resulting in \_\_\_. This leads to predominantly ___ hemolysis. Name 3 causes of oxidative stress.
Hb; splenic macrophages; bite cells; intravascular; fava beans; infections; drugs (primaquine, sulfa drugs and dapsone)
101
G6PD deficiency presents with ___ and ___ hours after exposure to oxidative stress. ___ is used to screen for the disease. __ confirm deficiency, but must be performed weeks after ___ resolves.
hemoglobinuria (classic of intravascular hemolysis); back pain (hgb is nephrotoxic); Heinz preparation (precipitated hgb can only be seen with Heinz stain); enzyme studies; hemolytic episode
102
What is seen in the picture? What disease do we see this in?
Heinz bodies (precipitated hgb can only be seen with special Heinz stain); G6PD deficiency
103
Immune hemolytic anemia (IHA) is \_\_-mediated (\_\_ or \_\_) destruction of RBCs.
antibody; IgG; IgM
104
In IgG mediated IHA, disease usually involves intravascular/extravascular hemolysis. IgG binds RBCs in warm/cold temperatures of the central/peripheral body. Membrane of antibody-coated RBC is consumed by ___ resulting in \_\_\_.
extravascular; warm; central; splenic macrophages; spherocytes
105
Name the 3 things IgG mediated IHA is associated with. Name the 4 tx.
SLE (most common), CLL (chronic lymphocytic leukemia), certain drugs (classicaly penicillin, cephalosporin); cessation of offendig drug, steroids, IVIG (splenic macrophages eat this instead), splenectomy (only if necessary)
106
In drug induced IgG mediated IHA, name the two mechanisms of action and a drug that does it.
1) drug can attach to the RBC membrane with subsequent binding of AB to the drug-membrane complex (penicillin); 2) drug can induce autoantibody production that binds self antigen on RBC (a-methyldopa)
107
IgM mediated IHA usually involves ___ hemolysis. IgM binds RBCs and fixes complement in the warm/cold in the central/peripheral body. RBCs inactivate complement, but residual ___ serves as an opsnoninn for ___ resulting in \_\_\_.
intravascular; cold; peripheral (extremities like fingers and toes); C3b; splenic macrophages; spherocytes
108
Name 2 things associated with IgM mediated IHA.
mycoplasma pneumoniae and infectious mononucleosis
109
\_\_\_ test is used to diagnose IHA. Testing can be ___ or \_\_\_.
Coombs; direct; indirect
(direct coombs test is themost impt test for IHA)
110
What is the difference between the direct and indirect coombs test?
Direct: are the RBCs already coated with IgG --\> add anti-IgG/complement to patient's RBCs, and if agglutination occurs, the RBCs are coated
Indirect: does the pt have ABs in their serum --\> anti-IgG and test RBCs are mixed w/pt's serum; agglutination occurs if serum ABs are present
111
Microangiopathic hemolytic anemia is ___ hemolysis that results from ___ pathology. RBCs are destroyed as they past through circulation.
intravascular; vascular
112
Name 5 potential causes of microangiopathic hemolytic anemia. What do you see on blood smear?
microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, aortic stenosis; schisctocytes (helmet cell)
113
Malaria is infection of ___ and liver with ___ transmitted by the female/male ___ mosquito.
RBCs; plasmodium; anopheles
114
In malaria, RBCs rupture as part of the \_\_\_\_, resulting in ___ hemolysis and cyclical fever. In which do you see daily fever, and in which do you see fever every other day? Spleen can also consume some infected RBCs resulting in mild ___ hemolysis with \_\_\_.
plasmodium life cycle; intravascular; P falcipru; P vivax and ovale; extravascular; splenomegaly
115
Anemia due to decrased production of RBCs by \_\_\_, is characterized by high/normal/low reticulocyte count. Name 3 etiologies.
bone marrow; low; causes of microcytic/macrocytic anemia; renal failure (dec production of EPO by peritubular interstitial cells); damage to bone marrow precursor cells (causes anemia or pancytopenia)
116
\_\_\_\_ infects progenitor red cells and temporarily halts EPO, which leads to significant anemia in the setting of pre-existing \_\_\_. Tx is supportive.
parvovirus B19; marrow stress (eg sickle cell anemia)
117
IgM mediated IHA is also called warm/cold agglutinin. IgG mediated IHA is also called warm/cold agglutinin.
cold; warm
118
Aplastic anemia involves damage to \_\_\_, resulting in ___ with a high/low retic count. Name three etiologies.
hematopoietic stem cells; pancytopenia; low; drugs/chemicals; viral infxns (eg parvovirus B19); autimmune damage
119
What is this an image of?
erythrocytes infected with malaria (specifically P falciparum)
120
When is this seen?
Aplastic anemia (empty, fatty marrow - pink circled part is bone)
121
Treatment of aplastic anemia involves these 5 things.
cessation of any causitive drugs; supportive care w/transfusions; marrow-stimulating factors (EPO, GM-CSF, and G-CSF); immunosuppression if causes is autoimmune; bone marrow transplant as last resort
122
\_\_\_ is a pathologic process (eg metastatic cancer) that replaces bone marrow. ____ is impaired, resulting in pancytopenia.
Myelophthisic; hematopoiesis
