Haematology Concept Tutorials

Question 1

Why might the blood cell count be low?

Answer 1

increased destruction
reduced production
redistribution

Question 2

Why might the blood cell count be high?

Answer 2

Increased production in response to stimulus
Increased production with no stimulus intrinsic (malignancy)
Redistribution

Question 3

What does anaemia mean?

Answer 3

Lack of red cells / haemoglobin

Question 4

What does -cytosis or -philia mean?

Answer 4

An excess of

E.g. neutrophilia, thrombocytosis

Question 5

What does -penia mean?

Answer 5

A shortage of

e.g. lymphopenia

Question 6

What does hyperplasia, dysplasia, hypoplasia and aplasia in term of marrow activity mean?

Answer 6

Hyperplasia - increased production
Dysplasia - disordered production
Hypoplasia - low production
Aplasia - no production

Question 7

What are the intact cellular mechanisms “machinery” generating red cells called?

Answer 7

The erythron

Question 8

B12 and folate are important for?

Answer 8

Catalyse important biochemical steps allowing cell division

Question 9

For the first few days after production, RBCs can be identified as?

Answer 9

Reticulocytes

Question 10

What happens to worn out RBCs?

Answer 10

Recycled to raw materials

Question 11

What controls the rate of RBC production in the bone marrow?

Answer 11

Hypoxia sensor

Question 12

What detects hypoxia in the blood flowing through the kidney?

Answer 12

Interstitial fibroblasts near to the peritubular capillaries and the proximal convoluted tubule

Question 13

Hypoxia to the body is anaemia, or a relative anaemia. What does this result in?

Answer 13

Increased production of the hormone erythropoeitin -> stimulate cell division of red cell precursors and recruits more cells to RBC production in the marrow

Result is erythroid hyperplasia i.e. more machinery to produce RBCs

Question 14

Draw a diagram of erythropoiesis

Answer 14

Question 15

If a woman comes in with a hx of coeliac disease. What would happen to erythropoeisis?

Answer 15

Low levels of raw material (iron) leads to low output (seen as an absence of an increase in reticulocyte count), as red cells wear out at a slow steady rate and not replaced so quickly,
Hb gradually drops
The sensing system identifies anaemia, increases erythropoietin levels and tries to stimulate marrow activity with mild to moderate hyperplasia.
But, as no raw materials, output remains low despite making more cells, that individually don’t contain much haemoglobin at all.
No change in rate of destruction of old red cells so no change in breakdown products.

Question 16

Scenario 1
24yr old woman presents with acute blood loss following the delivery of her third child. Bleeding is rapidly controlled by a combination of local pressure and oxytocin but she has lost approximately a litre of blood in a very short period of time.
Hb rapidly falls as she is given colloid to maintain her blood pressure
What immediate physiological changes be observed clinically?

Answer 16

Tachycardia
Hypotension
Peripheral shutdown
Predict increased stroke volume as a response to anaemia

Question 17

Scenario 1
24yr old woman presents with acute blood loss following the delivery of her third child. Bleeding is rapidly controlled by a combination of local pressure and oxytocin but she has lost approximately a litre of blood in a very short period of time.
Hb rapidly falls as she is given colloid to maintain her blood pressure
How will she respond to the anaemia to restore homeostasis?

Answer 17

Will try restore blood volume by redistributing fluid to circulation and increasing sympathetic tone in circulation

Hb falls as redistributes fluids / we give IV fluids

Brief burst in reticulocytes (stay in marrow few days before released so “mini pool” there) but oxygen sensor detects anaemia -> increases erythropoietin which stimulates markedly increased RBC production by the erythronium (erythroid hyperplasia), depleting stores which can’t be used at the rate they are being used up

Would see increase in new red cells being made so reticulocytes increased. Eventually Hb rises and drive to make epopoeitin fall as homeostasis achieved.

Waste products - unaffected, old cells die at same rate

Question 18

Scenario 1
24yr old woman presents with acute blood loss following the delivery of her third child. Bleeding is rapidly controlled by a combination of local pressure and oxytocin but she has lost approximately a litre of blood in a very short period of time.
Hb rapidly falls as she is given colloid to maintain her blood pressure
Any potential limitations to restoring homeostasis?

Answer 18

Reliant on plentiful stores as won’t be able to replace them as quickly as they are needed

Low blood pressure, pallor, dehydration, slow CRT, fast breathing, high pulse,
Trigger hypoxia sensor, trigger increased release of erythropoeitin, increased activity of the erythron (hyperplastic). As blood loss is stopped the blood count will return to normal as erythropoeisis is continuing as normal. Reduction in iron stores initially but
Limitations: reduced iron stores, and haem stores and reduced globin stores mean that the erythron will not work as efficiently as it should be

Question 19

Scenario 2
A 3 year old boy with glucose-6-phosphate dehydrogenase deficiency is anaemic. He has normal levels of the necessary materials to make haemoglobin but due to the deficiency in G6PD his red cells cannot withstand the oxidative stresses of normal life and so have a vastly reduced survival (30 days compared to the usual 120 days) in the circulation.
What are the consequences of this reduced red cell survival?

Answer 19

As cells die sooner, fewer in circulation so Hb drops. Stimulates erythropoeitin and increased RBC production so erythron increases in size (erythroid hyperplasia) using up stores and increased reticulocyte count is seen -> bringing up the Hb

In this case, unlike scenario 1, the RBCs are not lost to the system as in blood loss but recycled

Destroyed red cells are recycled, so see increased amounts of waste products (bilirubin) and the iron is sent back to stores to be used again so not iron deficient

Question 20

Scenario 2
A 3 year old boy with glucose-6-phosphate dehydrogenase deficiency is anaemic. He has normal levels of the necessary materials to make haemoglobin but due to the deficiency in G6PD his red cells cannot withstand the oxidative stresses of normal life and so have a vastly reduced survival (30 days compared to the usual 120 days) in the circulation.
Will he necessarily be anaemic?

Answer 20

Not if he can make cells as quickly as they are being destroyed (but will have high reticulocyte and bilirubin)

Question 21

Scenario 2
A 3 year old boy with glucose-6-phosphate dehydrogenase deficiency is anaemic. He has normal levels of the necessary materials to make haemoglobin but due to the deficiency in G6PD his red cells cannot withstand the oxidative stresses of normal life and so have a vastly reduced survival (30 days compared to the usual 120 days) in the circulation.

Any potential limitations to restoring homeostasis?

Answer 21

Folate deficiency potentially

A drop in haemoglobin, hypoxia sensor stimulated, increased erythropoeitin, increased activity of erythron (erythroid hyperplasia). Reticulocytosis (high reticulocye count) – will try build up the Hb. Breakdown products will increase, shorten RBC survival so they are destroyed quicker within the spleen. Splenomegaly and bilirubin would increase (hyperbilirubinemia) – jaundice. Increased iron stores because breakdown quicker.

If able to compensate, then no anemia. But if unable, or stressors like viral infection, can cause an episode of anaemia.
Potential limitations – any sort of kidney disease may delay restoring homeostasis. Erythron can only work so hard, so if demand outstrips production then you will struggle and become anaemic.

Question 22

Scenario 3
A 63 year old man with poorly controlled diabetes and progressive chronic renal failure. His kidneys are small and scarred on renal ultrasound. They no longer make erythropoietin in response to hypoxia.
What are the consequences to red cell production as the erythropoietin level gradually falls?

Answer 22

Starting with low erythropoietin then loss of stimulus to RBC production by erythron, so erythroid hypoplasia

Low reticulocyte count so Hb falls (rate of fall would be slow - only at the rate of natural destruction of old RBCs and compensatory mechanisms would kick in to improve oxygen delivery so may not be so symptomatic as in scenario 1

Closed system so iron would be recycled to stores which would increase, but bilirubin is continually lost to gut so would not.

Erythroid hypoplasia –> reticulocytopenia. Finite number of iron, if anaemic, iron will not be in RBCs. They will be in the iron stores. Injection of erythropoeitin will cause reticulocytosis and bring Hb up and hypoxia sensor will say its high enough and it will even off.

Question 23

Scenario 4
A 55yr old man who is a lifelong smoker. He has developed chronic obstructive pulmonary disease. He has finally managed to stop smoking and has seen the respiratory team who think he is a candidate for domiciliary oxygen for his chronic severe hypoxia due to type one respiratory failure.
What is the response in the kidney to chronic hypoxia?

Answer 23

Increase erythropoietin production

Body increases erythropoeitin, erythroid hyperplasia, increase in Hb (polycythemia), and then amino acid and bilirubin increase. Iron stores will go down because more RBCs are being made and this uses iron to produce haem.

Body is trying to restore homeostasis, so with time, when Hb returns to normal, Hb threshold will be increased. Eventually hypoxia sensro will be turned off. Iron stores lower over lnger period of time, so more iron absorbed.

If he gets home oxygen, more oxygen available so that downregulates hypoxia sensor, and then everything goes in reverse. Erythroid hypoplasia, erticulocytopenia, achieve homeostasis, and things will go back to normal.

Question 24

Scenario 4
A 55yr old man who is a lifelong smoker. He has developed chronic obstructive pulmonary disease. He has finally managed to stop smoking and has seen the respiratory team who think he is a candidate for domiciliary oxygen for his chronic severe hypoxia due to type one respiratory failure
How might this affect his red cell production?

Answer 24

Increased erythropoietin results in increased RBC production in erythron

This results in erythroid hyperplasia.

Chronic condition, so slow onset. iron will be used up but not rapidly as in scenario 1.

Increases in reticulocytes increase in Hb resulting in polycythemia. A new steady state will be achieved at the raised Hb, and the drive to the oxygen sensor will reduce - his system has effectively “reset” at a higher value. The increased red cell mass will need a slightly higher reticulocyte count to maintain but this will be hard to measure

when he starts home oxygen, through the same system his oxygen sensor will reset to a lower Hb

Question 25

Formative scenario 1 47yr old man with a history of Crohn’s disease affecting the proximal small bowel. As a consequence of malabsorption he has become folate deficient. He has pancytopenia and mild jaundice. Can you explain the jaundice?

Answer 25

Folate is essential for allowing cells in the marrow making blood to divide. Without folate even though cells have plenty haemoglobin the rate of division is markedly reduced so very few are made Some of the increased numbers of cells that are recruited are stuck in limbo and can’t divide are destroyed in the marrow. These cells that are able to synthesize hb but can’t divide need their hb recycled. The porphyrin rings are recycled to bilirubin, hence mild jaundice.

Question 26

Formative scenario 2 A 3 year old boy has, following a viral illness developed TEC (transient erythropenia of childhood). In this rare condition red cell production stops for a variable number of weeks. What would you see if his erythroid production had shut down for 4 weeks?

Answer 26

Red cell aplasia in the bone marrow

Question 27

Formative scenario 2 A 3 year old boy has, following a viral illness developed TEC (transient erythropenia of childhood). In this rare condition red cell production stops for a variable number of weeks. Would he be symptomatic?

Answer 27

Probably not, as it is transient and slow onset. Although Hb would fall compensatory mechanisms would improve oxygen delivery e.g. 2,3 BPG. It depends how long the aplasia lasted. Would try and avoid transfusion

Question 28

Formative scenario 2 A 3 year old boy has, following a viral illness developed TEC (transient erythropenia of childhood). In this rare condition red cell production stops for a variable number of weeks. What would be the first sign that he is starting to recover?

Answer 28

A reticulocytosis Erythropoietin would rise as anemia develops but with no erythroid hyperplasia (and so initially there would be a reticulocytopenia). Wouldn't see a significant change in bilirubin As iron is not being utilised by the erythron, the iron stores would accumulate as Hb falls until the erythron restarted as iron is not lost from the system

Question 29

Formative scenario 3 A 67 year old woman has developed a point mutation in Jak2 which results in constitutive activation of the Jak-stat pathway. This results in constant signalling through the erythropoietin receptor signalling pathway even without binding of erythropoietin so the cell ‘thinks’ that erythropoietin level is high. What is the consequences to the red cell production pathway?

Answer 29

Erythroid hyperplasia and rising Hb, epo levels fall. Normally this would mean that erythropoiesis would reduce (no epo binding so no signalling to nucleus to divide through the now silenced jak-stat pathway). But Jak-stat pathway is signalling all the time due to the mutation so cell division continues regardless at increased rate. Iron sometimes used up and the lack of iron might limit further rise in Hb. Contrast this primary polycythaemia to secondary polycythaemia in scenario 4. The problem here is the erthron is active because of an entrinsic problem with it and not responding to the falling epo levels.

Question 30

Formative scenario 4 A 49 year old woman presents with a two month history of increasing fatigue with stiffness and swelling of her hands, wrists and elbows. The stiffness seems to improve during the day. Her GP confirms a diagnosis of rheumatoid arthritis. Blood tests show she is anaemic, with raised inflammatory markers. You will learn about the mechanisms for anaemia of chronic disease later this week. They include reduced red cell survival, blunted epo production by hypoxia sensor/bluned epo response by the erythron and reduced iron availability. Considering these mechanisms in turn, how might each of these mechanisms affect red cell production?

Answer 30

Reduced epo - erythroid hypoplasia Reduced epo responsiveness – reduced erythropoiesis (erythroid hypoplasia) Reduced iron availability- iron deficient erythropoiesis Reduced red cell survival - in isolation would stimulate increased erythropoiesis but with the above other mechanisms the result is anaemia.

Question 31

What does thrombophilia mean?

Answer 31

Excess tendency to thrombosis