4.01 Page Summary - Anaemia

8/4/2019 4.01 Page Summary - Anaemia

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4.01 Iron Deficiency Anaemia

Any condition in which the number of red blood cells/mm3, theamount of Hb in 100mL of blood, and/or the volume ofpacked red blood cells/100 mL of blood are than normalCLINICALLY DEFINED AS: Concentration of oxygen-transporting material in a designated volume of blood (incontrast to total quantities as in oligocythemia,oligochromemia, and oligemia)

EPIDEMIOLOGY

30% of the total world population is anaemic

have Iron Deficienc 600 million eo le

RISK FACTORS & AETIOLOGY OF IRON DEFICIENCY:

1. Dietary lack2. Impaired Absorption3. Increased Requirement4. Chronic Blood Loss

5.Dietary lack: Infants, Children, Impoverished, Elderly

6.Impaired Absorption - Due to Absorptive disorders, Steathorrhea,Chronic Diarrhoea, Gastrectomy ( hydrochloric acid and transittime in duodenum)

7.Increased requirement.

Growing infants and children, adolescents, and premenopausal

(especially pregnant)

Risk: socioeconomic females with multiple, frequent

pregnancies

8.Chronic Blood Loss

Most common cause of iron deficiency in the Western world.

If bleeding occurs into tissues or cavities of the body, the hemeiron can be totally recovered and recycled.

However, external hemorrhage, as can occur from the GIT, the

urinary tract, or the genital tract, depletes iron reserves

t men and postmenopausal women in the Western world must beattributed to GIT blood loss until proven otherwise (important

PATHOPHYSIOLOGY

Iron Deficiency produces a Hypochromic Microcytic Anaemia.Simultaneously, depletion of essential iron-containing enzymes in cellsthroughout the body can cause other changes, including koilonychia,alopecia, atrophic changes in the tongue and gastric mucosa, andintestinal malabsorption.

- Reserves in the form ofFerritin andHemosiderin may be adequate to maintainnormal hemoglobin and hematocrit levels aswell as normal serum iron and Transferrinsaturation.

- Progressive depletion of these reserves firstlowers serum iron and transferrin saturationlevels, without producing anemia.

- In this early stage, there is increased erythroidactivity in the bone marrow.

- Anemia only appears when iron stores arecompletely depleted, accompanied by lowserum iron, serum ferritin, and transferrinsaturation.

Hypochromic microcytic anemia of iron deficiency (peripheral bloodsmear). Note the small red cells containing a narrow rim of peripheralhemoglobin. Scattered fully hemoglobinized cells, present due to recentblood transfusion, stand in contrast.Patients may be asymptomatic due to:

Slow Hb Haemodynamic Compensation & enhancement of O2-

carrying capacity of blood

2,3-DPG (aka: BPG) Right shift of O2 dissociation curve so that

CLINICAL FEATURES

General Symptoms (very non-specific)

Angina Dyspnea

Palpitations Intermittent

Claudication

Fatigue Headaches

Faintness

General Signs

Systolic Flow Murmur Cardiac failure

Tachycardia Pallor

Rarely: papilloedema & retinal haemorrhages after acute

bleed (can be accompanied by blindness).

SIGNS IN SPECIFIC ANAEMIAS

MICROCYTIC:

Iron Deficiency Anaemia

Tongue Papillae atrophy

Brittle Hair and Nails

Angular stomatitis

Koilonychia (spoon nails)

Epithelial changes

Dysphagia & Glossitis (Plummer-Vinson/Paterson-Brown-Kelly

syndrome)

NORMOCYTIC

Haemolytic Anaemia: Destroyed Cells Journey to the Spleen

Dark urine

Chills

Jaundice

Splenomegaly

Aplastic Anaemia: Bleeding, Infection & Bruising

MACROCYTIC

Megaloblastic Anaemias

Symptoms Malaise (90%) Dyspnea (50%)

Paraesthesiae (80%) Mouth soreness (20%)

Weight Skin pig. change

Grey hair Impotence

Memory Depression

Personality change Hallucinations

Visual disturbance

Signs

Pyrexia

Angular Stomatitis (Cheilosis)

Skin pigmentation change andVitiligo

Tongue Smooth

Heart failure

B12 Deficiency Additional Neuro Signs

Neurological disease in up to 40% of cases.

Focal demyelination affecting:

Ferritin: Iron-protein complex, containing ~23% iron; Ferric Ions + Apoferritin;

Found in intestinal mucosa, spleen, BM, reticulocytes & liver; Regulates ironstorage & transport from intestinal lumen to plasmaHemosiderin: Golden yellow or yellow-brown insoluble protein produced by

phagocytic digestion of hematin; found in most tissues, especially liver, spleen, andBM; In the form of granules much larger than ferritin molecules (of which they arebelieved to be aggregates); Higher content ~37% of iron; stains blue with PerlPrussian blue stain.Transferrin: Iron-transporting protein; Non-heme Beta -1 Globulin of the plasma,capable of associating reversibly with up to 1.25mcg iron/g. EXTRA


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DIAGNOSISBased on Hx & Examination (see clinical features)

FBCAnaemia indicated by Hb on FBC +/- Clinical features Furtherinvestigation based on MCV

RDW (Red cell distribution width; variation in the size of yourRBCs; demonstrates anisocytosis) may also assist in Normal MCV(normocytic anaemia), Low MCV (microcytic anaemia) and HighMCV (macrocytic anaemia)

Blood Film: Elicits hallmarks of cells indicating diagnosis or furtherinvestigation

FURTHER INVESTIGATION

MICROCYTICIron Deficiency Anaemia (IDA)

Hx Diet, meds (NSAIDs), bleeding (esp menstrual)

Blood Film

o Microcytic RBCs (MCV < 80 fL)

o Hypochromic (MCH < 27 pg)

o Poikilocytosis (variation in shape)

o Anisocytosis (variation in size)

o Target cells present

Iron Studies

o Plasma Ferritin - Best single test to confirm IDA

(Measures iron stores; very sensitive (other measuresaffected by many factors)

o Transferrin saturation of 120 fl

RCC for degree of anaemia

Blood Film Oval Macrocytosis, Poikilocytosis, RBCFragmentation, Hypersegmented Neutrophils

Retic count for degree of anaemia

Leuc count or N

Platelet count or N

Bone Marrow Cellularity, Megaloblastic changes in erythroidseries, giant metamyelocytes, dysplasticmegakaryocytes, increased iron in stores,pathological non-ring sideroblasts

Serum Ferritin

Plasma LDH often

Serum Bilirubin May be from ineffective erythropoiesis

Serum Vit B12 Schilling Test: usually


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NORMAL BONE MARROW FUNCTION

Bone marrow array of cells, specialized functions- Host defence (granulocytes, monocytes, lymphocytes ie white cells)- Oxygen transport (erythrocytes ie red cells)- Haemostasis (platelets released by megakaryocytes)

Haemopoiesis takes place in the bone marrow after7 months gestation,& priorto this in the fetal liver & spleen.

The haemopoietic stem cell:- is capable ofself renewal- is capable ofdifferentiation ("multipotent or pluripotent") to

erythroid, lymphoid ormyeloid (granulocytic, monocytic, erythroid,

or megakaryocyte) progenitors.- has no unique morphological characteristics & is morphologicallyidentical to a small to intermediate sized lymphocyte.

Exposure to haemopoietic growth factors stem cell becomescommitted (differentiation). Commitment to a lineage is irreversible &the capacity for self-renewal is lost as maturation progresses. Growthfactors continue to influence cell maturation & subsequently function.

Haemopoietic growth factors are produced by an array of haemopoietic& stromal cells which reside in the marrow.

EPO is an exception in that its main source is the kidneyGrowth factors are in general stimulatory although inhibitory factors alsoexist. Growth factors act in synergy with each other especially in lowconcentrations.

Bone marrow microenvironment provides a suitable structural, nutritional &hormonal environment for haemopoiesis. The microenvironment includes:

Stromal cells (macrophages, fibroblasts, reticulum cells, fat cells &endothelial cells). Stromal cells are one important source ofhaemopoietic growth factors & othercytokines. They have animportant role in haemopoietic cell adhesion, through cell adhesionmolecules, & hence determine the localisation of haemopoiesis.

Extra-cellular matrix (ECM including components such as:fibronectin, laminin, collagen & proteoglycans)

Microvascular network of thin walled venous sinusoids allowingcommunication with the rest of the body through the systemiccirculation

Some haemopoietic growth factors have established roles in cl inicalpractice eg EPO (erythropoietin), G-CSF (Granulocyte - Colony Stimulatingfactor) & GM-CSF (Granulocyte/Monocyte - Colony Stimulating Factor).Most common nutritional deficiency that lead to alterations inhaemopoiesis are deficiencies ofVitamin B 12, Folate & Iron

Other Factors Required for Normal Haemopoiesis (EspeciallyErythropoiesis):- Metals - iron, manganese, cobalt- Vitamins - vitamin B 12 , folic acid, vitamin C, E, B 6 , thiamine,

riboflavin & pantothenic acid- Amino acids

LIFE HISTORY OF RED CELL:GENERATION, LOSS & DESTRUCTION

Red cells - formed in the red marrow from Erythroid StemCells

Mature under influence of erythropoietin (EPO) through anumber of divisions leading from Erythroblasts Erythrocytes/RBCs

120 day life span. Normally balance b/wproduction/destruction

Production can be accelerated up to 7X fold if demand (Achieved by expansion of the volumeof red marrow andby shortening of the transit time for red cell maturation(skipped divisions).

Destruction after their 120 day life span may involvecontinual loss of membrane components, theaccumulation ofproductsofoxidated damage and/ordecreased deformability of the RBC Unable to squeezethroughtheminute (1-2 um) fenestrations in the splenicmicrovasculature Effete RBC finally phagocytosed bymacrophages of the Reticuloendothelial System, mainly inthe spleen but also in the Liver and BM. Phagocytosis ofRBCs becomes more prominent when red cell survivalis shortened (hemolysis).

Blood Loss Anaemia

Clinical signs are very different in anaemia:

Acute: Secondary to blood loss (following trauma or surgery)

Acute blood loss anaemia, there are changes in the pulseand BP and the patient may present in a state of shock(Very low BP, Rapid pulse, cold & discoloured extremities,sweating, dilated pupils etc)

"Reactive " thrombocytosis (raised platelet count) and areactive increase in white blood cells (leucocytosis) mayoccur.

Chronic (intermittent or slow bleeding from eg peptic ulcer orheavy menstrual loss - menorrhagia).

Compensating mechanisms which allow the patient tofunction in their day to day activities with relative ease.(Alteration in Hb function allowing oxygen release to thetissues more readily)

Chronic blood lossresults in iron deficiencyIt is clear that for a proper assessment of a person with bloodloss anaemia there are three critical processes:

- Careful history (abnormal bleeding, menstrualhistory in women, symptoms of peptic ulcer, alteredbowel habit etc.)- Physical examination - signs of acute bleeding, iron

CONSEQUENCES OF DEFICIENCIES OF ESSENTIAL HAEMATINICS

Deficiency of one or more of these elements involved in haemopoiesis AnaemiaDiagnosis relies on history, physical examination and laboratory tests, commencing with a blood count and examination of the blood film.Iron deficiency is the commonest cause of anaemia throughout the world. In underdeveloped countries this is due to gastrointestinal blood lossfrom hookworm infestation.In our society, the commonest cause of iron deficiency is menstrual blood loss in fertile women. This is so common as to be consideredalmost "normal for age". In older women and men, the diagnosis of iron deficiency which cannot be explained by obvious blood loss must be

followed by a search for a source ofoccult bleeding, possibly from a carcinoma of the gastrointestinal tract or from peptic ulceration of thestomach.Iron deficiency anaemia is also common in infants and young children due to poor iron intake.48711500 Dr Hambury Ronald Cooper chlormycetin eye drops - patientMICROCYTOSIS:The laboratory hallmark of iron deficiency is the presence of small red blood cells. This can be best appreciated from the electronically derivedmean corpuscular volume (MCV). Normal MCV is 80-100fl but in iron deficiency the MCV falls to under 80fl.Specific studies: serum iron level, serum transferrin and serum ferri tin (the best measurement of overall iron stored in the body).

MACROCYTOSIS:Reductions in the amount of folic acid orvitamin B 12in the body result in anaemia characterised by an increase in red cell size and specificappearances within the bone marrow (megaloblastosis).

- The MCV is over 100fl and the blood film shows large red cells and variations in size and shape.- There may also be changes in the neutrophils which can show marked nuclear hypersegmentation.- Not all causes of macrocytosis induce megaloblastosis of the bone marrow Excess alcohol consumption for example is the

commonest cause of macrocytosis in our community but is not associated with megaloblastic anaemia.Unlike iron deficiency, the lack of folic acid or vitamin B 12 is rather uncommon.Deficiency of vitamin B 12Can cause profound neurological damage. Lack of vitamin B 12 is most commonly caused by poor absorption from the bowel.

- Autoimmune disease known as pernicious anaemia Ab produced by the patient's own immune system destroys gastric cells whichnormally secrete a substance known as intrinsic factor.

- Intrinsic factor must bind to vitamin B 12 in the stomach for vitamin B 12 to be absorbed in the terminal ileum. When intrinsic factor is nolonger secreted vitamin B 12 absorption ceases.

- Other non-immune causes for vitamin B 12 deficiency also exist including surgical removal of stomach or terminal ileum.Folic acid absorption occurs in the jejunum and does not require intrinsic factor. Diseases affecting the small bowel (eg coeliac disease) orsurgical removal of large segments of small intestine can therefore impair its absorption. Some groups of patients with poor diets eg the elderly,severely depressed individuals and adolescents can also become deficient from inadequate folic acid intake.

Hemolytic Anemia - any anemia resulting from an increased rate of erythrocyte destruction


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HAEMOLYSIS - Premature Destruction of RBCs

RBC survives 120 days; shortening in time = haemolysis

Survival measurement: radiolabel RBC with Chromium-51 and re-inject, sample at intervals of several days to measure removal(rarely used)

Haemolytic Amaemia Lab Tests:

Hb Rapidly reduced due to either Haemolysis of Blood Loss. If

Haemolysis, confirm with clinical presentation of Scleral jaundice& splenomegaly (from RBC destruction)

Reticulocytes

Bilirubin (from haem breakdown from Hb)

Lactic DeH (LDH; found in RBCs)

Haptoglobulin Absent (haptoglobin binds haem and prevents

renal excretion)

Blood Film Examination look for morphological changes

Bone marrow examination (rarely performed) - May show

erythroid hyperplasis ( RBC precursors)

Coombs Test: Looks for Abs on the cell surface (direct

antiglobulin tests) if immune mediated hemolysis suspectedMechanisms of Haemolysis:

- Abnormalities of RBC membrane and underlying cytoskeletalproteins loss of surface lipid and spherocyte formation (eghereditary spherocytosis)

- Enzyme deficiencies in RBC: Commonest is G6P DeH (RBC cantmake NADPH antioxidant; Excessive oxidant stress denatures Hb Haemolysis)

- Abnormalities of the Hb structure or synthesis (inherited) (e.g. SickleCell and Thalassaemia)

- Autoimmune destruction in spleen and liver (due to production of

VITAMIN B12 AND THE NERVOUS SYSTEM

B12 involved myelin (and other protein) synthesis by glial cells

Deficiency fatty deposits in the myelin and coalesce (largestfibres most affected)

Slower AP conduction cant sustain high frequency information blocked transmission

May affect: (1) Peripheral Nerves, (2) Spinal Cord, (3) Brain

1. Peripheral Nerves - Peripheral Neuropathy of:Sensory Neurons:

Numbness and Parasthesias ("pins and needles") in hands andfeet, often symmetrically (glove and stocking distribution).

Due to slowing and asynchrony of APs in sensory neuronesMotor Neurons

Motor weakness due to wasting of peripheral muscles may occur

Stretch reflexes are diminished in affected regions2. Spinal Cord - Two major pathways affected in the white matter ofthe spinal cord (combined degeneration)

I. Dorsal Or Posterior Columns (will cause SensoryDifficulties, Proprioception loss (particularly in the dark), Loss ofthe sense of Vibration)

II. Lateral Corticospinal Tract (will cause Stretch

reflexes are exaggerated, Motor tone is increased, Babinski signis present)

3. Brain - Demyelination results in Confusion, Depression,Moodiness, Memory Losses, Overt Psychosis

Prognosis:

Symptoms rapidly resolve with B12 treatment

Recovery from demyelination and associated axonal damage


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OTHER MICROCYTIC HYPOCHROMIC ANAEMIAS

Anaemia of Chronic Disease- Normocytic, can be normochromic- Mild Hb rarely 95fl, as high as 120-140gl)- Macrocytes typically oval in shape- Reticulocyte count low,

- May be moderately reduced platelet and WCC- Hypersegmented neutrophils (6 or more lobes)- serum bilirubin, hydroxybuturate and lactate dehydrogenase as

result of marrow cell breakdown- Marrow hypercellular, large erythroblasts, giant and abnormally

shaped metamyelocytesPathogenesis:

Folate causes anaemia by inhibiting thymidylate synthesis, a ratelimiting step in DNA synthesis. Folate is delivered to cells as MethylTHF, which is a coenzyme for this reaction.B12 is also involved in this step as is demethylates methyl THF to THFto be used in synthesis of folate. the proximate cause of anaemia inB12 deficiency is folate deficiency see appendix 1 for more infoB12 and Pernicious anaemia: - due to autoimmune attack atrophyof stomach. Wall of stomachbecomes thin, plasma cell and lymphoidinfiltrate oflamina propria. There is achlorhydria and absent secretionof Intrisic Factor (IF) which is necessary for absorption of B12

Causes of microcytic anemia = TAILS: T- Thalassemia,A - Anemiaof chronic disease, I- Iron deficiency anemia, L - Lead toxicityassociated anemia, S- Sideroblastic anemia.


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Appendix 2

Intravascular haemolysisCaused by:

- mechanical injury: caused by defective cardiac valves, thrombi withinthe microcirculation, or repetitive physical trauma (marathon running,bongo drum beating) can physically lyse red cells.

- complement fixation: can occur on antibody-coated cells duringtransfusion of mismatched blood.

- infection by intracellular parasites such as falciparum malaria, orexogenous toxic factors: Toxic injury is exemplified by clostridialsepsis, which releases toxins that attack the red cell membrane.

Intravascular hemolysis is manifested by

hemoglobinemia and hemoglobinuria

jaundice

hemosiderinuria

Methalbuminaemia.

Decreased serum haptoglobin

Free hemoglobin in plasma is promptly bound by an 2-globulin

(haptoglobin), producing a complex that is rapidly cleared by themononuclear phagocyte system, thus preventing excretion into theurine.

When haptoglobin is depleted free hemoglobin prone to oxidation tomethemoglobin, which is brown in color. The renal proximal tubular

cells reabsorb and catabolize much of the fil tered hemoglobin andmethemoglobin, but some passes out with the urine, imparting a red-brown color. Iron released from hemoglobin can accumulate withintubular cells, giving rise to renal hemosiderosis. Concomitantly, hemegroups derived from the complexes are catabolized to bilirubin withinthe mononuclear phagocyte system, leading to jaundice. In hemolyticanemias, the serum bilirubin is unconjugated and the level ofhyperbilirubinemia depends on the functional capacity of the liver andthe rate of hemolysis. When the liver is normal, jaundice is rarelysevere. Excessive bilirubin excreted by the liver into the gastrointestinaltract leads to increased formation and fecal excretion of urobilin

Extravascular hemolysis

extreme alterations in shape are required for red cells to navigate thesplenic sinusoids successfully, reduced deformability makes thepassage difficult and leads to sequestration within the cords, followed

by phagocytosis. This is an important pathogenetic mechanism ofextravascular hemolysis in a variety of hemolytic anemias. Withextravascular hemolysis, hemoglobinemia and hemoglobinuria are notobserved, and its principal features are anemia and jaundice. However,some hemoglobin inevitably escapes from phagocytes, leading todecreases in plasma haptoglobin. The morphologic changes areidentical to those in intravascular hemolysis, except that "work"hyperplasia of the mononuclear phagocyte system often leads tosplenomegaly.

Appendix 1

Two reactions in humans are known to require vitamin B12.

1) Methylcobalamin is an essential cofactor for methioninesynthase, an enzyme involved in the conversion ofhomocysteine to methionine. In the process,methylcobalamin yields a methyl group and is regeneratedfrom N5-methyltetrahydrofolic acid (N5-methyl FH4), theprincipal form of folic acid in plasma.

2) In the same reaction, N5-methyl FH4 is converted totetrahydrofolic acid (FH4). FH4 is crucial, since it is required(through its derivative N5,10-methylene FH4) for conversion ofdeoxyuridine monophosphate to deoxythymidinemonophosphate, an immediate precursor of DNA

It has been postulated that the fundamental cause of impaired DNAsynthesis in vitamin B12 deficiency is the reduced availability of FH4,most of which is "trapped" as N5-methyl FH4.34In addition, the deficit inFH4 can be exacerbated by an "internal" folate deficiency caused by afailure to synthesize metabolically active polyglutamylated forms.35Thismay stem from a requirement for vitamin B12 in synthesis ofmethionine, which contributes a carbon group needed in the metabolicreactions that create folate polyglutamates. Whatever the mechanism of internal folate deficiency, lack of folate isthe proximate cause of anemia in vitamin B12 deficiency, as the anemia

inevitably improves with administration of folic acid.

WARM ANTIBODY IMMUNOHEMOLYTICANEMIA. - MOST COMMON FORM (48% TO 70%)OF IMMUNE HEMOLYTIC ANEMIA.- Mostly IgG but sometimes IgA- Mostly extravascular destruction- IgG-coated red cells bind Fc receptors onmonocytes and splenic macrophages, which resultsin loss of red cell membrane during "partial"phagocytosis.As in hereditary spherocytosis, the loss of cellmembrane converts the red cells to spherocytes,which are sequestered and removed in the spleen,the major site of red cell destruction in this disorder.

Thus, moderate splenomegaly is characteristic ofthis form of anemia.

Cold Agglutinin Immunohemolytic Anemia. -caused by so-called cold agglutinins, IgM antibodiesthat bind and agglutinate red cells avidly at lowtemperatures (0 to 4C).- accounts for 16% to 32% of cases- Antibodies appearacutelyafter mycoplasmapneumonia and infectious mononucleosis selflimited, clinical features rare.- Other infectious agents assoc. with this form ofinclude CMV, influenza virus, HIV.- Chronicanemias occur in association with certainlymphoid neoplasms or as an idiopathic condition.- Clinical symptoms binding of IgM to red cells at

sites such as exposed fingers, toes, and ears wheretemp


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Past Exams MEQs

2003 MEQ paper 1: Brian Murphy is a 77 year old man who presents toyour surgery complaining of tiredness and dyspnoea. You note that he ispale and has signs of heart failure. His haemoglobin measures 87g/L(normal range 125-165 g/L).1. Name 3 laboratory test results that would suggest the anaemia is due tohaemolysis rather than reduced red cell production.Model Answerraised reticulocyte count

positive direct antiglobulin (Coombs) testraised bilirubin levelabsent haptoglobin in serumraised serum LDH

presence of methaemalbumin in serum

2. a) Which components of the red cell are responsible for blood groups?b) The direct antiglobulin (Coombs) test is requested and is positive. Whatdoes the direct antiglobulin test detect?Model Answer

a) Surface glycoproteins and/or glycolipidsCellular carbohydrate transferasesb) The presence of immunoglobulin and/or complement on the surface ofred blood cells

3. Describe two possible mechanisms of destruction of circulating red cellswhich become coated with immunoglobulin/antibody.Model Answer(i) antibody fixes complement and red cells lyse in the circulation(ii) antibody fails to fix complement and red cells are removed fromcirculation in the liver or spleen via Fc receptors of reticulo-endothelial cellmacrophages)

4. The patient is treated with oral prednisone. Name two short term andtwo long term complications of oral corticosteroid administration.Model Answer

Short term: mood change, insomnia, hyperglycaemia, hypertension,Long term: obesity, skin thinning, bruising, cataracts, adrenalsuppression, osteoporosis, infection

2001 MEQ paper 1: Sarah Weiss is a 15 year-old girl who comes to theGP with her mother who is concerned that Sarah has lost weight, seemstired all the time and appears pale. Up until 10 months ago, Sarah was agood eater and was a normal and active girl. Her weight is now 58 kg(was previously 68 kg) and her height is 165 cm.The GP orders a full blood count (FBC) and blood film which show:

FBC Sarahsresults

Referencerange

Blood film

WCC 8.1 x 109/L 4.513.0 x109/L

Hypochromia +

Platelets 598 x109/L

150600 x109/L

Microcytosis +

Haemoglobin *81 g/L 120160 g/L Poikilocytes +

MCV *71 fl 7895 fl Pencil cells occasional(thin elongated cells)

MCHC *295 g/L 320360 g/L

1. RegardingSarahs blood filmand red cell indices,which 2 features aremost helpful insuggesting thecause of heranaemia is irondeficiency?Model AnswerHypochromia (asshown by lowMCHC) andmicrocytosis (asshown by low MCV)are characteristicfindings of irondeficiency anaemia.Other red cellchanges such as

pencil cells are less reliable indicators of iron deficiency. The plateletcount at the upper end of the normal range (borderline thrombocytosis)suggests that blood loss may be a factor.

2. You plan to do additional tests to confirm the diagnosis. List 3 additionalblood parameters you would test which would confirm a diagnosis of irondeficiency. Specify whether you would expect each to be high, low ornormal.Model AnswerConfirm the diagnosis of iron deficiency with appropriate iron studies (eg,low serum iron, high serum transferrin and total iron binding capacity, lowiron saturation, low serum ferritin)

For the past year Sarah has not eaten meat, fish, chicken, eggs, ormilk products. She changed to a vegan diet consisting of greenvegetables, legumes and cereals because of concerns about killing

animals and eating animal products.

3. a) Give 2 foods or food types which would have been the major sourcesof iron in her diet during the past year.b) How might the bioavailability of iron be increased in her diet?Model Answera) Cereals and legumesb) By taking in more foods containing vitamin C, eg, citrus, tomatoes.

2005 RFA 2: Cynthia Salakas is a 78-year old widow who presents withdyspnoea, palpitations on exertion and "pounding in the ears". She alsodescribes unsteadiness on standing with occasional falls. Mrs Salakaslives alone with no family support and prepares her own meals. Onexamination, she is pale and anxious, with a tachycardia of 100 beats/minand BP of 130/80. The spleen is just palpable but there is nolymphadenopathy.

A full blood count shows the following:

Indices Mrs Salakas' Results Normal Range

Hb 68 g/L 115 - 165 g/L

MCV 124 fl 76 - 96 fl

WBC 3.5 x 109/L 4.0 - 11.0 x 109/L


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Platelets 89 x 109/L 150 - 500 x 109/L

1. List at least THREE common causes of a macrocytic anaemia.Model AnswerLiver disease, Vitamin B12 deficiency, Folate deficiency, Alcohol excess,Myelodysplastic syndromes, Drug effect (drugs interfering with DNAsynthesis cytotoxics and immunosuppressive agents), Haemolysis orhaemorrhage (reticulocytosis)

She has had difficulty preparing her own meals over the past fewmonths as she feels very unsteady and has resorted to toastedcheese or tomato sandwiches several evenings per week as hermain meal. She often consumes only half to three-quarters of her

usual intake and she has noticed some weight loss which she isbecoming concerned about.2. What nutritional assessment methods could you use to decide if MrsSalakas is malnourished? (Give THREE)Model Answer1) Diet history and food frequency: ask the patient for all foods and fluidsconsumed over a typical week and how this may have changed over thepast few months-compare previous to now. Also do a food frequency ofmajor food items consumed over 1 week. Compare intake torecommendations for her age and gender. Consider the patients barriersto be able to obtain a normal intake.2) Anthropometry: ask the patient for a weight history over the past 6-12months.3) Laboratory results: consider the current results obtained and determineif further studies are required to determine if anaemia is likely due to poordiet and if the patient also has overall malnutrition.

Further testing shows a serum B12 level of 60 pmol/L (normal range130-600 pmol/L) with normal red cell folate level.3. Describe the typical blood film of B12/folate deficiency.Model AnswerVariable anaemia, red cells are macrocytic, with increased oval forms anda marked variation in size (anisocytosis) and shape (poikilocytosis),Variable leukopenia. Neutrophils show hypersegmentation (greater than 6lobes) with occasionalgiant forms (macropolycytes), Variable thrombocytopenia, with giantplatelets

You perform a neurological examination on Mrs Salakas. Herperception of position, sense and vibration is impaired in the feetand hands. Tendon reflexes are generally brisk with upgoing

plantars. Her gait is abnormal, with unsteadiness on walking.

4 a) Describe the location and nature of the pathological effects of B12deficiency on the nervous system.b) Describe at least TWO of the main neurological signs associated withB12 deficiency.

Model Answera) Primarily affects white matter of the dorsal and lateral columns of thespinal cord, and cerebral cortex Myelin degeneration and loss of nervefibres in dorsal and lateral tracts, nerve degeneration in dorsal root gangliaand peripheral nerves (subacute combined degeneration)b) Confusion, impaired memory, Sensory changes dominate symmetricaltered sensation, paraesthesiae in glove-stocking, distribution. Laterchanges include ataxia, gait problems, reduced vibration and positionsense, Upper motor neurone signs weakness, increased tendon reflexesand Babinskis sign, late in disease (lateral column disease).

Mrs Salakas is transfused initially and commenced on a course ofparenteral B12 replacement. After two weeks in hospital she feelsmuch improved and is anxious to return home.5. You are about to discuss handing over her care with her local GP. Listat least TWO community services or agencies that could provide supportfollowing her assessment as fit to go home. Give a brief explanation ofeach agency's role and why she might require their involvement.Model AnswerAgencies RoleHome/community nursing Supervision of medications, wound dressings,review of function at home, sometimes showering/personal hygieneHome care Assistance with cleaning home, showering/personal hygieneMeals on wheels MealsOT home assessment Minimise risk of falls from instabilityOutpatient physiotherapy and transportation Continued improvement ofneuromuscular function

2004 RFA 2: Soraya Mahfouz is a 73 year old woman, widowed one yearago. She has been brought to you, her GP, by her son who is concernedthat she is not coping. Mrs Mahfouz reports that she doesnt feel up tomuch, and while insisting that she is managing at home, is clearlyavoiding activity due to fatigue and breathlessness on exertion that hasbecome more of a problem in the last three months. She has lost 4-5 kg inthe last year but has no specific symptoms on system review other than

features of moderate depression. On examination she has pallor ofmucous membranes and nailbeds and you suspect that she is significantlyanaemic. She has no evidence of bruising or splenomegaly, but her liveredge is palpable 2 cm below the costal margin.

1. Identify two features from this womans history and/or examinationsuggestive of anaemia. For each of these features state why they aresuggestive.Model Answer* Fatigue and breathlessness with physical activity may reflect a rise incardiac output incompensation for a decreased erythrocyte mass* Pallor of mucous membranes and nailbeds these are sites which allowreliable detection ofpallor, from which one can infer a decrease in the oxygen-carryingcapacity of the blood

Her haemoglobin is 93 g/L, (normal range 115 - 165 g/L), meancorpuscular volume is 72 fL (normal range 80 - 100 fL) and meancorpuscular haemoglobin concentration is 295 g/L (normal range 310- 350 g/L). Platelet and white cell measures are normal, as is theblood film.2. Describe the physiology of red blood cell production. Pay particularattention to key nutritional components and any other relevant stimulatoryfactors.Model AnswerRed blood cells are produced in the bone marrow. They require numerousmicronutrients including iron for haem and vitamin B12 and folate whichare essential for maturation. The hormone erythropoietin stimulates theirproduction and is secreted in response to hypoxic conditions in the kidney,

such as after haemorrhage or in high altitude living.

3. What is the most likely micronutrient deficiency underlying this womansanaemia and why?Model AnswerThe most likely deficient micronutrient is iron, because the MCV and theMCHC are both reduced (microcytic, hypochromic anaemia). B12 andfolate deficiencies produce a megaloblastic anaemia.

4. List 3 additional blood parameters you would test which would confirm adiagnosis of iron deficiency. Specify whether you would expect each to behigh, low or normal.Model AnswerConfirm the diagnosis of iron deficiency with appropriate iron studies (eg,low serum iron, high serum transferrin and total iron binding capacity, lowiron saturation, low serum ferritin)

5. Describe the mechanisms by which the biochemical environment in thetissues mediates oxygen delivery to active cells from haemoglobin in redcells.Model AnswerIn active tissues, higher temperature, acid pH, high concentrations of CO2and 2,3- diphosphoglycerate (product of anaerobic glycolysis) all shift thehaemoglobin dissociation curve to the right, decreasing the affinity ofhaemoglobin for oxygen.

You confirm that she has a significant iron deficiency, with depletediron stores.6. a) What is the most likely cause of iron deficiency anaemia in a womanof this age?b) What tests would you recommend to confirm the most likely cause?Model Answer

a) In post-menopausal females, the commonest cause of iron deficiency isgastrointestinal blood loss.b) Gastroscopy and colonoscopy or other imaging of the gastrointestinaltract

7. Soraya is likely to need some services to help her live in thecommunity. A referral is made to the Aged Care Assessment Team(ACAT).a) Write a short paragraph describing, for Soraya and her son, the role ofthe ACAT team.b) Write another short paragraph explaining what they should know aboutCommunity Aged Care Packages (CACPs).Model Answera)* ACATs help older people and their carers work out what kind of care willbest meet their needs when they are no longer able to manage at home

without assistance* ACATs provide information on suitable care options and can helparramge access or referral to appropriate community or residential care*They are usually attached to hospitals or community centres* They provide thorough assessments of care needs* The team usually consists of doctors, nurses, social workers and alliedhealth professionals (including occupational therapists, physiotherapistsand speech therapists)


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* They are usually accessed via the local doctor or sometimes duringhospital admissionb)* Community Aged Care Packages (CACPs) are planned and coordinatedpackages of care to help older people remain living in their own homes* They may include help with bathing, showering or personal hygiene,social support, transport, laundry, meal preparation and gardening* The Australian Government provides a subsidy to local service providersand clients pay a portion of the fee (depending on their own income andability to pay)* For people on a basic pension, fees must not exceed 17.5% 0f thatpension.* People on higher incomes may be asked to pay additional fees (limitedto 50% of any income above the maximum pension rate)* Access to CACPs is only possible following an assessment and referralby the ACAT team

Past Exams SBAs

Case 6Mrs Mehar Singh is a 45 year old woman who complained of increasinglethargy over the past month and was found to have pale mucosa onexamination. Her blood count shows a haemoglobin of 90 g/L (115-165g/L) with mean cell volume of 60 fL (75-100 fL), white cell count of 6 x109/L (4-11 x 109/L) and platelets of 510 x 109/L (150-400 x 109/L). Her GPnotes that a previous haemoglobin result at the time of her hysterectomytwelve months ago was normal. Investigations demonstrate that she isiron deficient.

25. Further investigations should include:

1 A) Isotope tests of vitamin B12 absorption2 B) Bone marrow examination3 C) Upper endoscopy and colonoscopy4 D) Duodenal biopsy for adult coel iac disease

Answer C

26. The best immediate marker of a response to iron therapy would be:1 A) Normalisation of the platelet count2 B) Increasing reticulocyte count3 C) Increase in haemoglobin4 D) Reduction in pallor

Answer B

27. Which of the following is most correct regarding dietary ironabsorption?1 A) The major site of absorption is the lower small intestine2 B) Iron in eggs and vegetables is as well absorbed as iron inmeat3 C) Ferrous iron is more readily absorbed than ferric iron4 D) Increased body iron stores result in increased dietary ironabsorption

Answer C

28. Which one of the following proteins is the major carrier of iron inblood?1 A) Albumin2 B) Ferritin3 C) Transcobalamin

4 D) Transferrin

Answer D

29. Iron plays a key functional role for all of the following proteinsEXCEPT:1 A) Cytochrome oxidase2 B) Hemoglobin3 C) Insulin receptor 4 D) Myoglobin5Answer C

Case 4Ron Porter is a 53 year old solicitor who presents to his GP in Mosmanwith mild dyspnoea on exertion and a history suggestive of angina. There

is no history of blood loss. Results of a full blood count are given in thetable below. An occult blood test was performed on a stool specimen andreported to be negative. He is considered for a blood transfusion.

Indices Mr Porters Results Normal Range

Haemoglobin 75 g/L 130 180 g/L

MCV 65.3 fL 80 100 fL

MCHC 317 g/L 300 350 g/L

White Cell Count 4.7 x 109/L 4.0 11.0 x 109/L

Platelets 426 x 109/L 150 400 x 109/L

19. Which of the following disorders may manifest as hypochromicmicrocytic anaemia?1 A) Haemolytic anaemia2 B) Thalassaemia trait

3 C) Liver disease4 D) Acute blood loss

Answer B

20. Which one of the following series of results would be consistent withiron deficiency?1 A) Increased iron saturation, elevated serum ferritin, and normalserum transferrin2 B) Normal serum ferritin, reduced serum iron, and reduced totaliron binding capacity3 C) Reduced serum ferritin, reduced iron saturation, andincreased total iron binding capacity4 D) Reduced serum transferrin and reduced serum transferrinreceptor

Answer CExplanation:A-False: This pattern suggests haemochromatosis. B-False:This pattern suggests anaemia of chronic disease.C-True: Thiscombination is typical of iron deficiency. D-False: Serum transferrin andtransferrin receptor levels are typically elevated in iron deficiency.

21. Which of the following is correct about iron?1 A) Iron is more readily absorbed in the ferric (Fe3+) form2 B) Iron absorption is enhanced in the presence of ascorbate3 C) Transferrin is the main reservoir of iron in the liver4 D) Ferritin represents the major circulating form of iron

Answer BExplanation: The ferrous form of iron is more readily absorbed and iron isstored as ferritin, not transferrin. Transferrin is the major circulating ironbinding protein .

22. The transfer of oxygen from haemoglobin to the tissues is:1 A) Decreased by 2,3-diphosphoglycerate (2,3-DPG)2 B) Increased at low pH3 C) Not af fected by the storage of red cel ls at 4oC4 D) Enhanced by fetal haemoglobin

Answer BExplanation: 2,3-DPG lowers the affinity of haemoglobin for oxygen,thereby facilitating oxygen delivery to the tissues. Acidosis (lower pH)lowers the affinity of haemoglobin for oxygen, resulting in a shift to theright of the haemoglobin oxygen dissociation curve. The affinity foroxygen is greater in foetal than in adult haemoglobin.PBL Reference: 4.01, Lecture 1: Role of haemoglobin in oxygen deliveryto tissues

23. Which one of the following is the most likely cause of anaemia in MrPorter?1 A) Dietary iron deficiency2 B) Malabsorption3 C) Diverticulitis4 D) Gastrointestinal malignancy

Answer D

24. Which of the following red cell concentrate transfusions would beincompatible and cause a serious haemolytic transfusion reaction?1 A) Donor Group O RhD Negative to Patient Group A RhDPositive2 B) Donor Group A RhD Positive to Patient Group A RhDNegative3 C) Donor Group AB RhD Positive to Patient Group B RhDPositive4 D) Donor Group O RhD Positive to Patient Group AB RhDPositive

Answer C

Most examined material in SBAs

4.01Lec 3 Introduction to anaemia4.01 Lec 4 Iron deficiency4.04 LT1 Microcytosis4.01 LT3 Consequences of deficiency4.05 LT6 Iron metabolism,4.05 LT7 Tests of iron status in anaemia


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4.01 Page Summary - Anaemia