Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Heme Week 1 > Robbins pg 629-634 > Flashcards

Robbins pg 629-634 Flashcards

1
Q

What is anemia?

A

Anemia is defined as a reduction of the total circulating

red cell mass below normal limits leading to tissue hypoxia and other clinical manifestations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

In practice, anemia is usually diagnosed how?

A

reduction in hematocrit (ratio of packed red cells to total blood volume) and the hemoglobin concentration of the blood to levels that are below the normal range

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

In general, what causes microcytic

hypo chromic anemias?

A

disorders of hemoglobin

synthesis (most often iron deficiency)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

In general, what causes microcytic anemias?

A

Often stem from abnormalities that impair the

maturation of erythroid precursors in the bone marrow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is mean cell volume (MCV)? Normal?

A

the average volume of a red cell
expressed in femtoliters (fL)

normal: 80-100 fL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is mean cell hemoglobin?Normal?

A

the average content (mass) of
hemoglobin per red cell, expressed in picograms

normal: 27-33

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is mean cell hemoglobin concentration?Normal?

A

the average concentration
of hemoglobin in a given volume of packed red
cells, expressed in grams per deciliter

normal: 33-37

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is red cell distribution width?

Normal?

A

the coefficient of variation of red cell volume

normal: 11.5-14.5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Whatever its cause, when sufficient, severe anemia leads to certain clinical findings. Like?

A
  • pale appearance
  • Weakness, malaise, and easy fatigability.

-The lowered oxygen content of the circulating
blood leads to dyspnea on mild exertion.

  • Hypoxia can
    cause fatty change in the liver, myocardium (can lead to heart failure), and kidney.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

T or F. The effects of acute blood loss are mainly due to the loss of intravascular volume

A

T, which if massive can lead to

cardiovascular collapse, shock, and death.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

If a patient survives an acute blood loss, how is blood volume restored?

A

If the patient survives, the
blood volume is rapidly restored by the intravascular shift
of water from the interstitial fluid compartment

This fluid
shift results in hemodilution and a lowering of the hematocrit.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

The reduction in oxygenation in acute blood loss anemia triggers what?

A

increased
secretion of erythropoietin from the kidney, which stimulates
the proliferation of committed erythroid progenitors
(CFU-E) in the marrow.

It takes about 5 days for the progeny of these CFU-Es to mature and appear as
newly released red cells (reticulocytes) in the peripheral
blood leading to reticulocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which is better in terms of iron retention, internal or external bleeding?

A

internal.

The iron in hemoglobin is recaptured if red cells extravasate into tissues, whereas bleeding into the gut or
out of the body leads to iron loss and possible iron deficiency, which can hamper the restoration of normal red cell counts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does intense bleeding affect leukocytes?

A

If the bleeding is sufficiently massive
to cause a decrease in blood pressure, the compensatory
release of adrenergic hormones mobilizes granulocytes
from the intravascular marginal pool and results in leukocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the features of hemolytic anemias?

A

A shortened red cell life span below the normal 120 days

• Elevated erythropoietin levels and a compensatory
increase in erythropoiesis

• Accumulation of hemoglobin degradation products that
are created as part of the process of red cell hemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where does physiologic destruction of red cells occur?

A

within macrophages, which are abundant in the spleen, liver, and bone marrow (triggered by age dependent changes in red cell surface proteins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

T or F. In the great majority of hemolytic anemias
the premature destruction of red cells also occurs within
phagocytes

A

T, an event that is referred to as extravascular
hemolysis.

If persistent, extravascular hemolysis leads to a hyperplasia of phagocytes manifested by varying degrees
of splenomegaly.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is extravascular hemolysis commonly caused by?

A

alterations
that render the red cell less deformable. Extreme changes
in shape are required for red cells to navigate the splenic
sinusoids successfully

Reduced deformability makes this
passage difficult, leading to red cell sequestration and
phagocytosis by macrophages located within the splenic
cords.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the principle clinical features of extravascular hemolysis?

A
  • anemia
  • splenomegaly
  • jaundice
20
Q

What is haptoglobin?

A

an α2-globulin that binds free hemoglobin and

prevents its excretion in the urine.

21
Q

Why would a patient with extravascular hemolysis benefit from splenectomy?

A

Because much of the pathologic destruction of red cells occurs in the spleen

22
Q

What is intravascular hemolysis?

A

Intravascular hemolysis of red cells may be caused by
mechanical injury, complement fixation, intracellular parasites
(e.g., falciparum malaria)), or exogenous
toxic factors.

23
Q

What are the principle clinical features of intravascular hemolysis?

A
  • anemia
  • hemoglobinemia
  • hemoglobinuria
  • hemosiderinuria
  • jaundice
24
Q

What happens to the large amount of free hemoglobin released during intravascular (or extravascular) hemolysis?

A

The large amounts of free hemoglobin
released from lysed red cells are promptly bound by haptoglobin, producing a complex that is rapidly cleared
by mononuclear phagocytes.

25
Q

What happens as serum haptoglobin is depleted?

A

As serum haptoglobin is

depleted, free hemoglobin oxidizes to methemoglobin, which is brown in color.

26
Q

Is most of the free hemoglobin (and methemoglobin) excreted into urine in these cases?

A

The renal proximal tubular cells reabsorb
and catabolize much of the filtered hemoglobin and methemoglobin,
but some passes out in the urine, imparting a redbrown
color.

27
Q

How can hemolysis cause renal hemosiderosis?

A

Iron released from hemoglobin can accumulate

within tubular cells, giving rise to renal hemosiderosis.

28
Q

Why would red cell hemolysis cause jaundice?

A

Heme groups derived from hemoglobin-haptoglobin
complexes are catabolized to bilirubin within
mononuclear phagocytes, leading to jaundice.

.

29
Q

T or F. Unlike in

extravascular hemolysis, splenomegaly is not seen in intravascular hemolysis

A

T.

30
Q

In all types of uncomplicated hemolytic anemias, the
excess serum bilirubin is unconjugated. What does the level of hyperbilirubinemia
depend on?

A

The functional capacity of the liver and the rate of hemolysis.

When the liver is normal, jaundice is rarely severe. Excessive bilirubin excreted by the liver into the gastrointestinal tract leads to increased
formation and fecal excretion of urobilin, and
often leads to the formation of gallstones derived from heme pigments

31
Q

What are normoblasts?

A

Anemia and lowered tissue oxygen tension
trigger the production of erythropoietin, which stimulates erythroid
differentiation and leads to the appearance of increased
numbers of erythroid precursors (normoblasts) in the marrow. These are commonly seen in hemolytic anemias

32
Q

What else is seen in blood smears in anemia?

A
  • increased reticulocytes
  • The phagocytosis of red cells leads to the accumulation of the iron containing pigment hemosiderin, particularly in the spleen,
    liver, and bone marrow (hemosiderosis).
  • If the anemia is severe, extramedullary
    hematopoiesis can appear in the liver, spleen, and lymph
    nodes.
  • With chronic hemolysis, elevated biliary excretion of
    bilirubin promotes the formation of pigment gallstones (cholelithiasis)
33
Q

What is hereditary spherocytosis (HS)?

A

an inherited disorder
caused by intrinsic defects in the red cell membrane skeleton
that render red cells spheroid, less deformable, and vulnerable to splenic sequestration and destruction

34
Q

MOI of HS?

A

AD in most cases

The remaining patients have a more severe form of the disease
that is usually caused by the inheritance of two different defects (a state known as compound heterozygosity).

35
Q

What is spectrin?

A

red cell protein on the internal surface that consists of two polypeptide chains, α and β,
which form intertwined (helical) flexible heterodimers.

36
Q

How is spectrin oriented?

A

The “head” regions of spectrin dimers self-associate to form tetramers with other strands, while the “tails” associate with actin oligomers that span the membrane.

Each actin oligomer can bind multiple spectrin tetramers,
thus creating a two-dimensional spectrin-actin skeleton
that is connected to the cell membrane by two distinct
interactions.

37
Q

How is the spectrin-actin skeleton connected to the cell membrane?

A

Two systems:

1) system involving the proteins ankyrin and
band 4.2, binds spectrin to the transmembrane ion transporter,
band 3.

2) The second, involving protein 4.1, binds the
“tail” of spectrin to another transmembrane protein

38
Q

What is the average life span of HS red cells?

A

10-20 days (normal 120 days)

39
Q

What are the most common mutations resulting in HS?

A

The pathogenic mutations most commonly
affect ankyrin, band 3, spectrin, or band 4.2, the
proteins involved in one of the two tethering interactions,
presumably because this complex is particularly important
in stabilizing the lipid bilayer.

Most mutations cause
frameshifts or introduce premature stop codons, such that
the mutated allele fails to produce any protein

40
Q

T or F. Young HS red cells are normal in shape

A

T, but the destabilized lipid bilayer sheds membrane
fragments as red cells age in the circulation. The loss of membrane relative to cytoplasm “forces” the cells to
assume the smallest possible diameter for a given volume, namely, a sphere (aka spherocytosis).

41
Q

Does splenectomy help HS patients?

A 
The invariably beneficial effects of splenectomy prove that the spleen has a cardinal role in the premature demise
of spherocytes (via macrophages).

Again, this is because red cells must undergo extreme deformation to leave the cords of Billroth and enter the sinusoids.

42
Q

How do spherocytes appear?

A

small, dark-staining (hyperchromic) red cells lacking the central zone of pallor

NOTE: spherocytes are seen in other pathologies (AHA)

43
Q

What are the clinical features of HS?

A
  • anemia
  • splenomegaly
  • jaundice

The severity varies greatly.

44
Q

Diagnosis of HS?

A

The diagnosis is based on family history,
hematologic findings, and laboratory evidence. In two
thirds of the patients the red cells are abnormally sensitive
to osmotic lysis when incubated in hypotonic salt solutions,
which causes the influx of water into spherocytes with little
margin for expansion. HS red cells also have an increased
mean cell hemoglobin concentration, due to dehydration
caused by the loss of K+ and H2O.

45
Q

HS

A

In a small
minority (mainly compound heterozygotes) HS presents at
birth with marked jaundice and requires exchange transfusions.

In 20% to 30% of patients the disease is so mild as to
be virtually asymptomatic; here the decreased red cell survival
is readily compensated for by increased erythropoiesis.

In most, however, the compensatory changes are
outpaced, producing a chronic hemolytic anemia of mild
to moderate severity.

46
Q

The generally stable clinical course of HS is sometimes punctuated
by aplastic crises. What is this?

A

usually triggered by an acute parvovirus
infection.

Parvovirus infects and kills red cell progenitors, effectively causing red cell production to cease until an immune response commences, generally in
1 to 2 weeks.

Because of the reduced life span of HS red
cells, cessation of erythropoiesis for even short time periods leads to sudden worsening of the anemia.

Transfusions
may be necessary to support the patient until the immune
response clears the infection.

Hemolytic crises are produced
by intercurrent events leading to increased splenic destruction
of red cells (e.g., infectious mononucleosis); these are
clinically less significant than aplastic crises. Gallstones,
found in many patients, can also produce symptoms.
Splenectomy treats the anemia and its complications, but
brings with it an increased risk of sepsis, since the spleen
acts as an important filter for blood borne bacteria.

Heme Week 1 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions