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Week 231

Anaemia in Adult Males is considered as an Hb Value less than what?



Week 231


Anaemia in Adult Females is considered as an Hb Value less than what?

Hb <11.5 g/dl


Week 231


What is an Erythrocyte?

This is a fully developed red blood cell.


Week 231


How many new Erythrocytes are made each day?

1012 New Erythrocytes


Week 231


What is the primary site of EPO synthesis?

The peritubular cells of the kidneys (Renal cortex).


Week 231


How is EPO production triggered?

EPO is not stored. Like most physiological cycles, it is a negative feedback cycle. The production of EPO is triggered by tissue hypoxia (oxygen tension in the tubules of the kidney).


Week 231


What is the major stimulant for EPO production?



Week 231


Chronic renal disease/Bilateral nephrectomy will stop or reduce the production of which growth factor?



Week 231


A failure of production of EPO causes what type of Anaemia?

Normacytic anaemia. The red cells will be a normal shape and size, but there will be less of them.


Week 231


In cases of chronic haemolysis, as in thalassaemia, EPO production rises as a result of chronic hypoxia. What effect(s) does this have?

An increase in EPO eads to an increase in the numbers of erythrocytes (red blood cells), resulting in expansion and eventually fatty deposition within the bone marrow. In children, this can cause growth deformities like Frontal Bossing.


Week 231


When do reticulocyte counts rise?

  • Haemorrhage
  • Haemolytic anaemia
  • Treatment of a haemotinic deficiency


Week 231


What is the ratio of reticulocyte to red blood cell count in a normal human being?


1:100 Reticulocyte:Red blood cell


Week 231


What is a pronormoblast?

This is the earliest stage of the erythrocyte, formed from stem cells. They have a large nucleus, and no haemoglobin.


Week 231


What are normoblasts?

A precursor to red blood cells. There is still a nucleus, but through the many variations of normoblasts, this gradually decreases. Eventually it is extruded from the cell and released into the blood.


Week 231


What % of the final Haemoglobin do reticulocytes contain?



Week 231


What is anaemia of chronic disease?

Anaemia of chronic disease. Within any individual who lives with a chronic disease (eg rheumatoid arthritis),a complex interaction of
inflammatory cytokines interferes with the red cell lifecycle by
impairing iron metabolism and inhibiting red cell precursors.
The end result is a normocytic anaemia.


Week 231


If asked to "check the haemotinics", what do you look at?


Vitamin B12




Week 231


Iron content is rate-limiting for erythropoiesis. So, in iron deficiency anaemia, the cells are ___. This is known as ______ ______.

The red cells are smaller in size This is known as microcytic anaemia.


Week 231


What is the term used to describe low haemoglobin?



Week 231


Vitamin B12 and Folate are used for which two important processes?

DNA Synthesis and Cell Mitoses.


Week 231


A Vitamin B12 or a folate deficiency leads to what?

These are important for DNA production and cell mitosis. A Lack means that cell formation and production happens more slowly. It leads to the productino of magaloblasts (enlarged, misshapen cells)!


Week 231


How much Ferrous Iron is absorbed from the small intestine every day in a healthy adult?



Week 231


Which protein does Iron attach to in the serum, and what is its function?

The protein is called Transferrin. It binds to iron, and transports it to the bone marrow.


Week 231


Which receptors are increased in iron deficiency?

Soluble Transfferin receptors. sTfR.




Week 231


What is ferritin?

It is a storage compound. Stored in the liver.


Week 231


Where are dying red blood cells recycled?

The spleen. This is where iron is recycled into the plasma for future use.


Week 231


Describe the iron deficieny PROFILE.

  • Serum Iron is reduced
  • Serum total iron binding capacity is increased. The body is working hard to bind any iron that is left.
  • Serum ferritin is reduced since iron stores are low.
  • Serum soluble transferrin receptors are increased since any iron in the system is being used up.


Week 231


Give causes of Vitamin B12 deficiency

  • Pernicious anaemia
  • Inadequate intake
  • Poor absorbtion



Week 231


What is the leading cause of B12 deficiency?

Pernicious anaemia.

  • Igg autoantibodies target parietal cells, and its product (intrinsic factor IF)
  • This basically means that less B12-IF is absorbed in the terminal ileum. BAD TIMES.


Week 231


What are the four proteins of importance in red blood cells?



Protein 4.1




Week 231


Defects in the structural proteins that form red blood cells can cause what?

These cells cannot withstand the shear forces of the microcirculation. Their shape changes (eg they become elliptical). These then get destroyed within the spleen by macrophages. This is haemolytic anaemia.


Week 231


Hereditary spherocytosis and elliptocytosis are examples of what?

Haemolytic anaemia. These are both due to defets in the Spectrin, one of four major protein components in the red blood cell.


Week 231


What is Thalassaemia?

There is a reduced rate of synthesis of either alpha or Beta globin chains. Within this group of inherited conditions, there may be both ineffective erythropoiesis, and haemolysis, leading to hypochromic (low iron) normacytic (normal size) anaemia.


Week 231


What is sickle-cell disease?

There is an inheritance of two abnormal Beta chains (HbSS).  The abnormality is a point mutation. This causes insolubility in the cells deoxygenated state, and crystalisation within the red blood cell. This...leads to sickle cell deformity, and vascular occlusion. Most often seen in Afro-Carribean populations.


Week 231


What is 2,3 - diphosphoglycerate?

This sits in between beta chains in haemoglobin, and helps to offload oxygen.


Week 231


The change from foetal to adult haemoglobin occurs at 3-6 months. What is the difference between adult and foetal haemoglobin?

Foetal Haemoglobin has a higher affinity for oxygen than adult haemoglobin.


Week 231


In metabolic alkalosis, what happens to the oxygen dissociation curve?

With an increased pH, CO2 is decreased, and the curve shifts to the LEFT. This means there is a higher affinity for oxygen in the lungs, and it is "harder" to release oxgen to tissues. This also occurs with foetal haemoglobin.


Week 231


How is the oxygen dissociation curve affected in metabolic acidosis?

Decreased pH, raised concentration of 2,3-DPG H+ ions. Shift to the right. This means greater release of O2 into the tissues.


Week 231


What is the role of the reticuloendothelial system?

Simply? This cleans up dead and dying/out of date cells.


Week 231


What are haemolytic anaemias?

A group of anaemias that lead to a shorteneed life span of red cells.


Week 231


What is LDH, and why is it useful?

This is a nucleic enzyme, released on red cell destruction. It's measurable in a blood sample, and is a useful indicator of haemolysis.


Week 231


When investigating haemolysis, what three things do you assess?

  1. Lactic acid dehydrogenase (LAD)
  2. Reticulocyte count
  3. Billirubin



Week 231


How does haemolysis cause Jaundice?

Excess uncojugated billirubin can occur from the breakdown of haem groups.


Week 231


What are the defining levels of Haemoglobin, for anaemia in Males and Females?

Males: 13.5 g/dl

Females: 11.5 g/dl


Week 231


How is the total circulating haemoglobin concentration determined?

  • The circulating plasma volume
  • The total circulating haemoglobin mass



Week 231


How may pregnancy or splenomegaly cause anaemia?

These can cause in increase in plasma volume, effectively reducing heaemoglobing concentration, though circulating levels may appear normal.


Week 231


What is the end result of anaemia?

Tissue hypoxia is the end result of reduced oxygen carrying capacity in the red blood cells.


Week 231


What are the two key compensatory mechanisms in place that act in response to tissue hypoxia from anaemia?

  1. Cardiac compensation. This is the major adapter. Both Stroke volume and heart rate increase to bring about a subsequent increase in cardiac output. This can present as palpatations or heart murmurs.
  2. Commonly, a generalised pallor is observed. This is generally due to a vasoconstriction, with redistribution of blood to key areas.


Week 231


Name some of the general clinical signs and symptoms of anaemia.

  • Headaches
  • SOB
  • Palpitations
  • Confusion and symptoms of cardiac failure
  • Weakness and lethargy
  • Glossitis
  • Angular Stomitis
  • Koilonychia
  • Dysphasia/Pharayngeal web



Week 231


Name some causes of microcytic, hypochromic anaemia.

Iron Deficiency





Week 231


What causes Normocytic normochromic anaemia?


Chronic Disease

Marrow infiltration



Week 231


What causes Macrocytic megaloblastic anaemia?

Folate deficiency

B12 deficiency



Week 231


G6PD deficiency and hereditary spherocytosis cause what type of anaemia?

Haemolytic anaemias.


Week 231


A Microcytic RBC has a MCV of what?

An MCV of LESS than 80fl


Week 231


Is a macrocytic blood film an indicator of excess alcohol consumption or liver disease?

Yes it is!


Week 231


Name three conditions in which target cells are found in peripheral blood films.

  1. Liver disease (obstructive jaundice)
  2. Thalassaemia major
  3. Sickle cell anaemia



Week 231


In which conditions do you observe fragmented RBC's on peripheral blood film?




Cardiac Valve (synthetic)



Week 231



In which conditions does peripheral blood film show tear drop poikilocytes?

  • Myelofibrosis
  • Extramedullary haemopoiesis



Week 231


Ringed RBC's on peripheral blood film are a sign of which condition?

Malaria infection from P falciparum.


Week 231


Prickle type RBC's pn peripheral blood film are indicative of which condition?

Pyruvate Kinase deficiency


Week 231


What is the most COMMON cause of IRON DEFICIENT anaemia?

Blood Loss


Week 231


What is Beta-Thallasemia?

This is a microcytic hypochromic anaemia. It is one of the most common autosomal inerited disorders.


Pathology is reduced beta globin production, from ineffective erythropoiesis and haemolysis.


Week 231


What is the fundamental difference between warm and cold autoimmune haemolytic anaemias?

  • Warm is associated with production of IgG
  • Cold is associated with production of IgM


Week 231


What are the functions of the haemopoietic system?

  • Transport: cells, oxygen, hormones, drugs
  • Surveilence: Cells, cytokines, proteins
  • Temperature regulation: Blood flow control


Week 231


What are the component parts of the haemopoietic system?




Bone: Scaffold (medulla protected by cortical bone) and cells (stroma)

Blood: vessels (endothelium) and cells (circulating)

Lymph: vessels and cells (circulating, nodes and extra lymphatic tissues,Spleen, Thymus



Week 231

The bone marrow produces which two elements of the haemopoietic system?

Cells, and stroma (connective tissue)


Week 231


What do plasma cells produce?



Week 231


What are the sites of prenatal blood production?

  • Yolk sac
  • spleen
  • bone marrow
  • Bone marrow


Week 231


What are the main sites of postnatal blood production?

  • Tibia
  • Femur
  • Rib
  • Sternum
  • Vertebra and pelvis


Week 231


B and T lymphocytes, and Natural Killer cells are derived from which earlier cell?

Lymphoid stem cell


Week 231


Granulocyte monocyte progenitor cells produce which cell types?

  • Monocyte
  • Neutrophils



Week 231


Erythroid progenitors produce which type of cell?

Red blood cell


Week 231


Megakaryocyte progenitor cells produce what?



Week 231


In a patient with acute renal failure, which agents would use to ensure adequate production of red blod cells?

Erythropoietin stimulating agents (ESA)


Monitor haemoglobin to find appropriate dose.  Aim for increase of no more than 20g/l over 4 weeks


Week 231


What is Hydroxocobalamin?

IM injection suitable B12 supplement.


Week 231


What does stem cell factor cause?

An increase in haemopoietic stem cell reproduction.


Week 231


(Granulocyte-Monocyte Colony Stimulating Factor) -
Stimulates what?

↑MPC (myeloid progenitor cell)
differentiation into granulocyte & monocyte lineage


Week 230


Where is Thrombopoietin produced, and what is it's effect?

Produced by
liver & kidneys
megakaryocyte → platelet


Week 231


- Granulocyte Colony Stimulating Factor -


What does it do?

- Accelerates
production &
maturation of neutrophils
(+ inhibits neutrophil apoptosis


week 231


Neutrophils take 12 days to produce - but how long do they spend in circulation?

Just 12 hours!


Week 231


A trephine is usec as part of which invasive investigatory procedure?

Bone marrow biopsy


Week 231


What (physiologically) hapens to cause
Idiopathic Thrombocytopenic Purpura?

Autoantibodies opsonise platelets, causing their lysis in the spleen.


Week 231


Name two drugs that are known triggers for idiopathic thrombocytic purpura.




Week 231


What wil the FBC show in
Idiopathic Thrombocytopenic Purpura?

Isolated thrombocytopaenia (often a compensatory increase in megakaryocytes too).


Week 231


 A 30 year old man with:


  • Fever
  • Petechiae/Purpura
  • Jaundice
  • Signs of Anaemia
  • Pallor
  • fatigue
  • Altered mental state,
  • seizures
  • focal pathologies
  • Haematuria --->Acute Renal Failure,
  • Hypertension

IVX show:

  • Thrombocytopenia
  • Anaemia, RBC Fragments
  • Unconj Bilirubinaemia
  • ↑Urea
  •  ↑Creatinine

I have given every possible symptom here -- so what does the poor fellow have?

Thrombotic Thrombocytopenic Purpura


Week 231


WHat is the pathophysiology of thrombotic thrombocytopenic  purpura?


  • von Willebrand Factor Multimers circulate in blood
  • Congenital form - Pts lack ADAMTS13 enzyme which cleaves vWF multimers
  • Acquired forms (more common) - Autoantibodies antagonise enzyme -->Platelets clump & cause ‘white’thromboses in small vessels -Mostly platelets content, little fibrin/RBCs
  • Thromboses & deposition damages organs incl. kidneys, CNS
  • Adults predominantly affected


Week 231


What is the pathophysiology of Haemolytic Uraemic Syndrome?

  • Entero-haemorrhagic E-Coli 0157- Produces
  • shiga-like toxin which Causes platelet-agglutination & "white thromboses" in small vessels
  • Similar pathology to TTP
  • Young Children mostly affected, but does occur in adolescents & adults


Week 231


In severe B12 deficiency, IM injection of which drug (every 3 months) is used?



(1mg 3xweekly for 2 weeks, maintenance dose 4xyr)
Can cause; Rash, chills, and hypokalaemia


Week 231


Which important vitamin is required to convert folic acid into folate?

Vitamin B12


Week 231


When is Folic acid given (OTHER THAN PREGNANCY)?

In megaloblastic anaemia, and when Methotrexate is given (it reduces the side effects)


Week 231


Name two iron chelators, that can be used in cases of iron overload or iron poisoning.

  • Desferrioxamine - IV or subcut. IV for poisoning, SC for overload
  • Desferasirox - This is given ORALLY. Causes gut irritation, so take on empty stomach, and avoid other irritants like NSAIDS.

Hearing and visual disturbances occur with both


Week 231


Name two Erythropoiesis Stimulating Agents.

  • EPO Alpha and Beta. These are recombinant forms used in renal failure and post-chemo.
  • Darbepoietin/Mircera - This are EPO receptor agonists, with longer half lives.
  • CAN CAUSE: Red cell Aplasia (Bone marrow not producing RBC's), hypertension and iron deficiency