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Year 2 PBL > Unit 9: Major Pernicious Anemia > Flashcards

Unit 9: Major Pernicious Anemia Flashcards

1
Q

Why does anemia cause tiredness?

A

Low arterial O2
Less oxygen perfusion to tissue, reduced respiratory rate, leads to a lower metabolic rate.
Causing fatigue

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2
Q

Why does PA cause breathlessness?

A

Low arterial O2. - detected by peripheral chemoreceptors. (aortic arch and vagus nerve, carotid bodies and glassopharangeal nerve)
Severe anemia may cause elevated CO2 - detected by central chemoreceptors
Signals are transmitted along afferent neurons to the medulla oblongata
Acts on the respiratory control centre, result in activation of the SNS, signals sent along the phrenic nerves and intercostal nerves to increase rate of respiration.

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3
Q

What is the life cycle of a red blood cell?

A
  1. haemopoietic stem cell
  2. Common myeloid progenitor (CFU-GEMM)
  3. Erythroid progenitors BFU-E and CFU-E
  4. Early pro-erythroblast - ribosome manufacturing
  5. Late pro-erythroblast - Hb accumulation
  6. Normoblast
  7. Reticulocyte
  8. Erythrocyte
    This process is guided by growth factors.
    Process occurs in the red bone marrow. Stimulates by EPO production in the kidney due to hypoxemia.
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4
Q

How does VitB12 deficiency affect blood cell development?

A

VitB12 is required for proliferation of erythroblasts, as used in DNA production.
Without it can’t produce mature erythrocytes, results in megaloblastic anemia.
Also affects DNA production in wbc - resulting in hypersegmented nuclei in neutrophils

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5
Q

Why in a suspected anemia case would a doctor ask about medication?

A

Drugs associated with anemia:
- metformin
- cephlasporins, penicillin and levofloxacin - immune hemolyitic
- NSAIDs (bleeding in GI)
- acetaminophen
- methyldopa ( to treat high BP) in an immune hemolyitic
- levodopa (to treat parkinsons) causes microcytic due to a vitamin B6 deficiency.

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6
Q

Why do you check for signs of dehydration in differential diagnosis of PA?

A

Dehydration may be present due to rapid reduction in blood volume, such as GI bleeding which can also cause normocytic anemia.

Dehydration can also cause microcytic anemia with reduced Hb, do to waters role in Hb production

Dehydration - may be sign of diabetes - differential diagnosis for tiredness

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7
Q

Why do you check for jaundice in a differential diagnosis for PA?

A

Jaundice - accumulation of bilirubin
Can indicate a haemolytic anaemia

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8
Q

Why did the doctor check fingernails in differential diagnosis for PA?

A

Clubbing fingernails - indicate GI malabsorption - indicate atrophic gastritis - related to cause of B12 deficiency.

Iron deficiency anaemia would present with pale and spoon shaped nails (koilnychia)

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9
Q

Why did the doctor check her tongue in differential diagnosis of PA?

A

Look for signs of glossitis - indicates of vitamin B12 deficiency, PA - low oxygen flow to tongue, results in atrophic gastritis

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10
Q

Why did the doctor check for gait and recent falls in a differential diagnosis of PA?

A

Fatigue may indicate stroke, this can be assessed by watching for difficult in limb movement.
Anaemia is a risk factor for falls is assessing this risk.
Assessing for brain injury, mental activity takes more energy can result in rapid mental fatigue.

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11
Q

Describe how PA may present on a full blood count.

A

Increased MCV
Decreased or same serum Vitamin B12
Decreased wbcs and platelets
Decreased reticulocyte count
Haemoglobin decrease
Haematocrit decreased
MCH - decreased
LDH and bilirubin increase - as immature RBCs are destroyed

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12
Q

What additional blood test is normally done to confirm a PA diagnosis?

A

MMA and HC levels may be elevated
Intrinsic factor auto-antibodies or/and parietal cell auto-antibodies may be present.
If auto-antibodies against parietal cells are identified may run an addition Intrinsic Factor assay to identify the level still being produced.

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13
Q

How does the immune system produce antibodies against patients own parietal cells and intrinsic factor?

A

Autoimmune condition
Managed to evade central and peripheral tolerance
Apoptotic components of parietal cell cleared by a macrophage and presented as foreign on MHC2 to T cell in the lymph node.

Is a complex autoimmune disease, is influenced by both genetic and environmental factors.

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14
Q

Why does anti-parietal cell antibodies lead to a deficiency in VitB12?

A

Lack of intrinsic factor secretion from parietal cells

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15
Q

Why do anti-intrinsic factor antibodies lead to a deficiency in VitB12?

A

Lack of intrinsic factor - less binds to VitB12 - decreased ability of VitB12 to be absorbed in the ileum as unable to bind to IF receptor

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16
Q

Why is hydroxocabalamin given more frequently during the first two weeks of treatment, then reduced?

A

Higher doses first to increase deficiency to normal level
Dose can then be decreased as simply need to maintain level.

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17
Q

Why is hydroxocabalamin given IM rather than orally in treatment of autoimmune PA?

A

Most cases of PA are unable to absorb VitB12, and already have sufficient B12 in their diet - orally administered B12 would also not be absorbed

Must be given in a way that can be quickly absorbed into blood stream to bypass the absorption process in the ileum.

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18
Q

What health problems does VitB12 deficiency pause a risk factor for?

A

Anaemia
GIT symptoms - associated with chronic atrophic gastritis such as vomiting, diahorrea, abdominal pain, weight loss
Neurological symptoms - loss of memory, loss of cognitive reasoning and changes in behaviour.

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19
Q

What are some of the potential health problems for a menopausal woman?

A

Osteoporosis - lack of oesotrgen results in lack of bone mineral density.
UTIs - change in oesotrgen alters vaginal walls can affect normal microflora
Cardiovascular disease - increased risk of atherosclerosis.

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20
Q

Why does vitamin B12 deficiency affect the nervous system?

A

Deficiency results in eegernateion of myelin sheath and atrophy of neural tissue
Due to accumulation of methylmalonate (abnormal lipid in the neurons) and lack of myelin sheath synthesis .
Mainly affects sensory nerves resulting in peripheral neuropathy and cognitive changes.

VitB12 aids the conversion of methymalonyl coenzyme A to succinyl coenzyme A.
Deficiency leads to a build up methylmalonic acid.
This causes the development of abnormal fatty acids in neuronal lipids
Leads to degeneration of myelin sheath, hence spinal cord.

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21
Q

What are the different types of autoantibody that can be produced in PA?

A

Type 1: blocks IF binding site for VB12
Type 2: blocks binding site of VB12 and IF complex to copulin receptor
Type 3: Bind to sub-units of gastric proton pump causing degeneration of parietal cells

22
Q

How are erythrocytes destroyed?

A

After 120 days are considered old or damaged erythrocytes
Are degraded in the spleen
Are phagocytosed by macrophages in the red pulp.
Haemoglobin is broken into heme and globin, globin is then broken in amino acids, heme to billirubin and Fe2+
Fe2+ and amino acids are transported back to the bone marrow by the blood
Billirubin is metabolised in the liver and excreted in bile

23
Q

What is the role of transferrin?

A

Binds to Fe3+, aids its transport in the blood

24
Q

What is polycythemia?

A

An excess of erhtrocytes - increased risk of blood clots.
Can cause liver and spleen enlargement
Hypertension and hypervolemic
Heart failures

25
Q

Where can rbc production go wrong?

A
  • kidney failure causing low EPO
  • destruction of bone marrow (autoimmune, drug or radiation)
  • deficiency of iron, vitB12, vitC or folic acid
26
Q

What is hypoplastic anemia?

A

Reduced erythropoesis

27
Q

What is aplastic anemia?

A

no erythropoiesis

28
Q

What is hemolytic anemia?

A

Premature destruction of rbcs
- inherited - typically from defect within the rbcs such as sickle cell and thalassemia
- acquired from overactive spleen, infection (malaria) and drugs.

29
Q

What can fingernail clubbing indicate?

A

Cyanotic heart disease
Lung disease
UC/Crohns disease
Biliary cirrhosis
Birth defect
Inefective endocarditis
Neoplasm
GI malabsoprtoin

30
Q

Why does PA affect the level of platelets and wbcs?

A

Affects the differentiation of Haematopoietic stem cells
Decreased DNA production affects the proliferation of cells so reduced counts

31
Q

What is the role of VB12 in DNA production?

A

Involved in a chain of reactions, in one of which VitB12 accepts a methyl group from the precursor for tetrahydrofolate. Hence a lack of vitamin B12 decreases levels of THF. THF depletion inhibits the conversion of dUMP to DTMP (thymidylate synthesis) leading to a lack of DNA production.

32
Q

Describe how vitamin B12 is absorbed in the body?

A

Saliva contains R-binder (hepatocorrin)
In stomach protein bound vitamin B 12 is released by pepsin
Binds to R-binder to prevent further digestion
Intrinsic factor is produced by parietal cells.
Transport to the ileum.
Pancreatic juices containing proteases cause the splitting of R binder VB12 complex
IF binds to VB12.
IFVB12 binds to IF receptors on enterocytes in ileum.
VB12 is taken up by pinocytosis and binds to transcobalamin 2 for delivery to the tissues.

33
Q

What are some of the main differences between PA and iron deficient anemia?

A

PA - macroblastic, typically autoimmune in cause, more common in older women, more common in scandinavian populations

Iron - microcytic, typically dietary in cause, common in pregnant and menstruating girls, more common in the black ethnic group

34
Q

What are the different cell types in the gastric gland and what do they secrete?

A

Goblet cells - mucus
Parietal cells - HCl and intrinsic factor
Chief cells - pepsinogen
D cells - Somatostatin
G cells - Gastrin

35
Q

Describe how anti-gastric parietal cell antibodies can lead to anemia?

A

Cause autoimmune gastritis
1. Leads to reduced intrinsic factor
2. Leads to achlorhydia leading to reduced iron absoprtion and reduced release of VB12 bound to protein leading to iron deficient and pernicious anemia.

36
Q

What is another term used for VB12?

A

Cobalamin

37
Q

What is achlorhydria?

A

A condition where the stomach does not produce HCl, lipase or pepsin.

38
Q

How common are autoimmune disease? Are they increasing in prevalence - long covid?

A

1 in 10 individuals are affected by an autoimmune disease
Increasing in prevalence - increase environmental risks such as smoking, alcohol.
Long covid - chronic inflammation - increased risk of autoimmune disease. More research needed to understand the linking factor

39
Q

How might metformin treatment for type 2 diabetes lead to vitamin B12 deficiency?
Can this be corrected by supplementation?

A

Risk increases with higher dosease and longer exposure.
Believed to interfere with VB12 absorption - mechanism is not yet fully understood
1. Alter gut microbiome - affecting levels of inflammation hence function of parietal cells
2. Altered intestinal motility - reduced absorption of all nutrients
3. Interferes with calcium ion dependent binding to IF receptor in terminal ileum

40
Q

Which foods are high in VB12? Should vegetarians take care of this in their diet?

A

Typically found in animal derived products such as fish, meat, eggs, milk.
Can also be found in fortified cereals that have been modified to have VitB12

Vegetarians should try to maintain a high dairy consumption or take VB12 supplements

41
Q

Does the efficiency of VB12 absoprtion change with age? Why/why not?

A

Yes - decreases with age
Often have lower levels of HCl and pepsin
May be malnutrition related
Result of surgery removing part of stomach/bowel
More likely to have developed crohns.
Older - more medications that have an affect on absoprtion such as NSAIDs and metformin.

42
Q

What are the risk factors for PA?

A

Family history of this condition or other autoimmune conditions
Surgical removal of parts of stomach or ileum
Intestinal infection or disease (crohns)
Medications - NSAIDs, metfromin, cephlasporins
Vegetarian/vegan

43
Q

What are the treatments for PA with neurological signs?

A

If neurological signs of deficiency contact haematologist, recommed intial hydroxyocobalamin 1mg intramuscularly on alternative days until an improvement is seen, then instramuscularly every 2 months should be considered

44
Q

What are the distinctive features symptoms of PA?

A

Glossitis
Peripheral Neuropathy
Changes in cognition
Gastrointestinal disturbances

45
Q

What does PA look like on a blood smear?

A

Macroblasts
Hypersegmented neutrophils
Reduced plaetelets
Anisopoikilocytosis - vary in shape and size
Typically are more ovoid in appearance

46
Q

What are the treatments for autoimmune PA with no neurological signs?

A

Hydroxocobalamin 1mg intramuscularly three times a week for 2 weeks
Maintenance: 1mg intramuscularly every three months for life if deficiency is not diet related
Maintenance: 50mg orally cyanocobalamin tablet daily or twice yearly 1mg injection if diet related

47
Q

Why is hydroxocobalamin used in PA treatment?

A

Is the manufacture form of VB12 (cobalamin)

48
Q

What are the features of an iron deficienty anemia blood smear?

A

microcytic cells
Increased paleness in centre - due to lack of Hb
May have hypersegmented neutrophils but this is rarer
Decreased number of rbcs

49
Q

What is the criteria for an anemia diagnosis?

A

RBC count below
13.5g/dL in men
11.5g/dL in women

50
Q

What is the Shilling test in PA? purpose?

A
  1. Given intramuscular B12 – staruates body binding sites
  2. Given oral radioactivly labelled VB12 – is absoprtion is functioning normally all should be absorbed into the blood stream then excreted in the urine
  3. Quantity of radiolabelled B12 can be assayed in the urine, compared to expected amount, decrease indicates not absorbed.

If not absorbed indicates autoimmune not a dietary problem.

51
Q

What are the long term associated risks with not treated with PA?

A

Increased risk of gastric cancer - due to chronic inflammation of the stomach, changes to DNA and epigenetics.

52
Q

List some different types of anemia

A

Haemolytic - inhertied (sickle cell) or acquired (drug use)
Aplastic - disease of bone marrow
Mircocytic - iron deficient
Macrocytic - folate or vitamin B12 deficient.

Year 2 PBL (27 decks)

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