Brainscape's Knowledge GenomeTM

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


See full index

Fundamentals of Pathology > W10 RBC production + survival > Flashcards

W10 RBC production + survival Flashcards

1
Q

Hormonal Control of Erythropoiesis

A

Imbalance so stimulus = Hypoxia due to decreased RBC count, decreased amount of hg or decreased availability of O2

Reduced O2 levels in blood

Kidney + liver (smaller extent) release erythropoetin

Erythropoetin stimulates red bone marrow

Enhanced eryhtropoiesis increases RBC count

Increases O2 carrying ability of blood

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

What else besides EPO?

A

Iron

Vitamin B12

Folate

Erythroid precursors

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

Iron sources

A

Meat, eggs, vegetables, dairy foods

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

Iron absorption

A

Normal Western diet provides 15mg daily.

5-10% absorbed (1mg) principally in duodenum and jejunum.

Gastric secretion (HCl) and ascorbic acid help absorption

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

Causes of Iron deficiency

A

Decreased uptake:
Inadequate intake
Malabsorption

Increased demand:
Pregnancy
Growth spurt

Increased loss:
GI bleed
Excess loss in menses

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

Vitamin B12 and Folic Acid

A

Both essential for RBC maturation & DNA synthesis

Both needed for formation of thymidine triphosphate.

B12 is coenzyme for methionine synthase in methylation of homocysteine to methionine.

Deficiency in either of them causes abnormal & diminished DNA, leading to failure of nuclear maturation

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

Causes of Vitamin B12 deficiency

A

Inadequate intake:
Vegans

Absorption defect:
Tropical sprue
Coeliac dx
Blind loop syndromes

IF deficiency:
Pernicious anaemia
Crohn’s
Gastrectomy & others

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

Causes of folate deficiency

A

Inadequate intake:
Poor nutrition

Absorption defect:
Coeliac disease
Crohn’s dx
Tropical sprue

Demand/ losses:
Pregnancy
Haemolysis
Cancer

Drugs:
Anticonvulsants

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

What happens in folate & B12 deficiencies?

A

Megaloblastic anemia, with macroovalocytes
and hypersegmented neutrophil

Treatment:
B12 - Hydroxycobalamin: 1mg im

Folate: -Folic acid: 5mg/day oral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Hydroxocobalamin

A

an injectable form of vitamin B12 that is given when there are problems with absorption of this vitamin from the gut

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

Absorption of B12

A

Involves IF made by gastric parietal cells.

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

TC1 is secreted by

A

TC1 is secreted by salivary glands and protects B12 from degradation

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

Vitamin B12 main foods

A

Animal origin only:

Liver, meat, fish

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

Vitamin B12 daily requirement

A

1-2µg

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

Vitamin B12 body stores

A

2-3mg
(sufficient for
2-4yrs)

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

Vitamin B12 absorption site

A

Ileum

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

Vitamin B12 transport in plasma

A

Bound to TCI; TCII for uptake

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

Folate main foods

A

Especially liver, greens & yeast

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

Folate daily requirement

A

100-150µg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Folate body stores

A

10-12mg

for 4mths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Folate absorption site

A

Duodenum, Jejunum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Folate transport in plasma

A

Weakly bound to albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What else can affect of RBC prod?

A

Renal dx - ineffective erythropoiesis

Reduced BM erythroid cells
Aplastic anaemia
Marrow infiltration by leukaemia or other malignancies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Red cell deformability

A

squeezing through a splenic sinus

25
Q

Ability of RBC to survive depends on

A

Cytoplasmic enzymes involve in metabolic pathways because mature RBCs have no nucleus, mitochondria or ribosomes;
therefore…unable to carry out oxidative phosphorylation and protein synthesis

26
Q

Stress placed on RBC

A

life span 120 days

300 miles travelled through microcirculation

7.8 m diameter

capillaries as small as 3.5 m

27
Q

AIHA

A

Autoimmune hemolytic anemia

Caused by antibody production by the body against its own red cells: divided into cold and warm depending on whether the antibody reacts more strongly with red cell at 37oC or 4oC

28
Q

Red cells are usually coated with

A

Red cells are usually coated with IgG alone or with compliment, therefore taken up by the RE macrophages. Destruction occurs generally in the RE

29
Q

Immune

A

Autoimmune

Alloimmune

Drug induced

30
Q

Non-immune

A

Red Cell fragmentation

Infection:

Secondary

31
Q

Haemoglobinopathies

A

Hereditary
Sickle cell diseases
Thalassaemias

32
Q

Red Cell enzymopathies

A

Hereditary
G6PD deficiency
PK deficiency

33
Q

Red Cell membrane disorders

A

Hereditary spherocytosis

Hereditary elliptocytosis

34
Q

Hereditary spherocytosis

A

Loss of membrane integrity, the RBCs become spherical

Common hereditary haemolytic anaemia in N. Europ.

deficiency in proteins with vertical interactions between the membrane skeleton and the lipid bilayer

35
Q

Hereditary elliptocytosis

A

Clinically milder

- mutations in horizontal protein, spectrin, leading to defective spectrin-Ankyrin association

36
Q

Two main enzymes

A

Two main enzymes
Glucose-6-Phosphate Dehydrogenase (G-6-PD)
Pyruvate Kinase (PK)

Support 2 main Metabolic Pathways
Pentose Phosphate pathway
Glycolytic pathway

37
Q

GSH protection of Hb + RBC membranes

A

Hb and rbc membranes are usually protected by reduced glutathione (GSH) from oxidant stress from the exposure to H2O2, certain medications, foods, or even infections. Heinz bodies are oxidised, denatured Hb

38
Q

NADPH

A

a role in protecting the red blood cell from oxidative damage

NADPH in turn is required for the maintenance of reduced
glutathione (GSH)

39
Q

GSH

A

acts as an anti-oxidant
G6PD catalyses the first step in the hexose monophosphate shunt which is necessary for producing NADPH

a tripeptide that protects the RBC from oxidative damage

40
Q

What happens in G6PD deficiency?

A

NADPH and GSH generation impaired

Acute haemolysis on exposure to oxidant stress: oxidative drugs, fava beans (broad beans) or infections

Hb precipitation – Heinz bodies

G6PD deficiency most common known enzymopathy, estimated to affect 400 million people worldwide.

…….but have evolutionary benefit

41
Q

G6PD def. X-linked

A

G6PD deficiency is X-linked, and seen in the same ethnic groups as haemoglobinopathies

42
Q

Patients w/G6PD def. have to avoid

A

have to avoid particular oxidative drugs, e.g. sulphonamides, dapsone, and notably quinone based anti-malarial drugs

43
Q

G6PD def. leads to

A

leads to HA upon treatment with primaquine which stimulates H2O2 formation

44
Q

G6PD def. patients protected from

A

patient have protection against severe malaria

45
Q

Glycolytic pathway

A

Generates ATP
to maintain red cell shape and deformability

regulates intracellular cation conc. via cation pumps (Na/K pump), 3Na+ out 2K+ in

46
Q

PK def. results in

A

PK is an autosomal recessive disorder, with more than 100 mutations documented, resulting in low intracellular ATP generation affecting membrane structure.

47
Q

“block” in glycolysis =

A

causes a build up of glycolytic intermediates, including 2,3 biphosphoglycerate, which binds to and shifts the oxygen dissociation curve to the right
2,3 diphosphoglycerate

48
Q

What happens in PK deficiency

A

ATP is depleted:

cells lose large amount of potassium & water, becoming dehydrated & rigid.

because cation pumps fail to function.

causes chronic non-spherocytic haemolytic anaemia

excess haemolysis leads to jaundice, gallstones

49
Q

What do we see when we have G6PD def.

A

film shows blistered cells (arrow), arrowheads show irregularly contracted cells

50
Q

What do we see w/PK def.

A

autosomal recessive, anaemia may worsen at times of infection or other stress; dense red cells with spicules (prickle cells) may be seen on the peripheral blood film

51
Q

Defects of band 3, spectrin, ankyrin, or protein 4.2 lead to

A

destabilisation of the overlying lipid bilayer and release of lipid in microvesicles

52
Q

Mutations or deletions may lead to;

A

Abnormal synthesis of globin chain as in Sickle Cell Diseases.

Reduced rate of synthesis of normal globin chains as in Thalassaemia.

53
Q

The genes for globin chains occur in…

A

clusters on chromosomes.
11 (ε, γ, δ and β)
16 (ζ and α 1+2)

54
Q

Normal adult blood has 3 types of Hb

A

HbA (α2β2), HbF (α2γ2), HbA2 (α2δ2)

55
Q

Group of Hb disorders with inherited sickle beta-globin gene

A

Sickle Cell Anaemia (HbSS), homozygous, most common;

heterozygote conditions: HbS/ßthal, HbSC, HbSD

56
Q

SCA definition

A

point mutation leading to single amino acid change in beta-globin (sub of valine for glutamic acid; A to T)

It’s the clinically most impt abnormality

57
Q

SCA details of mutation

A

HbS/βthal, MCV & MCH are lower than HbSS, clinical picture is of SCA, splenomegaly
Hb C – lysine replaces GA at position 6
Hb D glutamine replaces GA
Hb E lysine replaces GA at position 26

58
Q

Beta-thalassaemia

A

Loss of 1 beta-chain causes mild microcytic anaemia (thalassaemia trait)

Loss of both (beta^0) causes thalassaemia major

Excess α-chains precipitate in erythroblasts causing haemolysis and ineffective erythropoiesis

59
Q

Alpha-thalassaemia

A

There can be loss of 1, 2, 3 or 4 alpha chanis

Fundamentals of Pathology (23 decks)

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