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110 Cards in this Set
- Front
- Back
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What is the lifespan of RBCs?
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120 days
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How can we increase production of RBCs?
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- Expansion of the number of precursors
- Shortening of transit times during maturation ie skipping some divisions / steps |
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If we need to, by how many fold can we increase our RBC production?
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7 fold!
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What are the three things we think are involved in the destruction of RBCs after their lifespan?
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1. Continual loss of membrane components
2. Accumulation of products of oxidative damage 3. Decreased deformability of the cell when it gets old -> can't squeeze through the fenestrations in the microvasculature of the spleen |
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What would we see with acute anaemia due to blood loss? ie what are the clinical signs?
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Signs of shock: low BP, racing pulse, cold and clammy, dilated pupils, discoloured extremities
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Where does haemopoiesis take place in the fetus?
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Fetal liver and spleen
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From what time in gestation do we have haemopoiesis happening in the BM?
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About 7 months gestation
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Where are haemopoietic growth factors produced?
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In the BM (by the haemopoietic and stromal cells)
EXCEPT EPO - it's produced in the kindey |
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Where is EPO produced?
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The kidney
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What are some examples of the cell types that are considered 'stromal cells' in the BM?
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Macros, fibroblasts, reticulum cells, fat cells and endothelial cells
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What is the role of the stromal cells in the BM?
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- Produce GFs and cytokines that direct and control haemopoiesis
- Important in haemopoietic cell adhesion and hence they are involved in determining the localisation of haemopoiesis |
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What are the three main groups of cells / things that make up the BM micro-environment?
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- Stromal cells
- Extracellular matrix - Microvascular network |
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What is B12's role in the nervous system?
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It's required by glial cells for their production of myelin
Also involved in the production of some neuronal proteins |
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What happens to nerves when we're deficient in B12?
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Fatty deposits accumulate in the myelin and coalesce
-> damage to the myelin -> conduction is slowed and then eventually completely blocked |
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When we have B12 deficiency affecting nerves, is it high or low frequency transmission that is lost first?
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The high frequency is lost first
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When we're deficient in B12, what sort of nerves are mostly affected?
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The larger fibres are more affected
And it affects the peripheral nerves, spinal cord and brain |
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What are the clinical features as a result of B12 deficiency affecting the peripheral nerves?
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Affects both the motor and sensory neurones
Person will get tingling / pins and needles Usually symmetrical, following glove and stocking distribution Also have muscle weakness and might get diminished stretch reflexes |
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What are the two pathways in the spinal cord that are affected by B12 deficiency?
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1. Dorsal / posterior column aka spinothalamic tract - this carries sensory info up to the brain
2. Lateral column aka corticospinal tract - this carries motor information down from the brain |
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What does damage to the dorsal /posterior column of spinal cord by B12 result in?
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Dorsal / posterior column carries SENSORY INFORMATION
The two things that are mostly affected are: 1. Proprioception 2. Sense of vibration This is because they're both carried by large fibres and B12 deficiency usually affects the larger fibres |
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What does damage to the lateral column of spinal cord by B12 result in?
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Lateral = MOTOR
Damage -> unsteadiness when walking (this is also related to loss of proprioception) |
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With B12 deficiency, in the absence of any peripheral neuropathies, what would neuropathies in the spinal cord do to the stretch reflexes?
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They would be more exaggerated. This is becuase you don't have the connections with the upper motor centres telling the limb not to reflex too much
Would also have the Babinski sign - big toe is extended, all others are flexed |
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What is the Babinski sign?
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Big toe is extended, all the others are flexed
Due to neuropathy in the spinal cord |
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What clinical signs result from neuropathy in the brain due to B12 deficiency?
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Confusion, depression, moodiness, memory losses and even overt psychosis
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If we give someone with B12 deficiency B12 treatment, which of there symptoms will recover rapidly and which won't?
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Cerebral manifestations (confusion etc) will resolve rapidly
The signs due to demyelination in the spinal cord and peripheral nerves are much slower to recover, especially when the symptoms are long-standing |
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What is the definition of under-nutrition?
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Inadequate nutritional intake to meet the metabolic demands and to maintain health
Deficient in energy protein and/or other nutrients |
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Why is under-nutrition a worry in the elderly?
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It's significant predictor of morbidity and mortality
And most of the time it's preventable and treatable |
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What percentage of elderly people living in the community are under-nourished?
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5-12%
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What percentage of elderly people in high care are under nourished?
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23-85%
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What has been shown to be associated with under nutrition?
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- Hospital admissions
- ED admissions (more likely to have 2+) - Time spent in hospital (more likely to spend more than 4 weeks in hospital) - Fall frequency |
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How many kcal / kg of body weight do we need each day?
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about 25-30
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How many grams of protein p/ kg of body weight are we meant to have each day?
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1-1.5g
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A baby girl born now - what's her life expectancy?
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85
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Baby boy born now - what's his life expectancy?
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79
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What is old person's pension p/week?
How much of this is taken away if you live in a nursing home? |
They get about $350 p/week
Govt takes 87.5% of that if they're living in a nursing home |
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How much iron do we need each day?
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About 1-2mg
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Where in the body is iron absorbed?
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The duodenum
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Where is iron stored in the body?
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Liver and macrophages
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What proportion of the circulating transferrin is saturated in a normal healthy person?
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ABout 1/3
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Which form of iron does transferrin bind?
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Fe3+ ie ferric iron
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What happens to transferrin levels if you're deficient in iron? And transferrin saturation?
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Transferrin levels increase because essentially body is desperately trying to grab all the iron that it can
Saturation will obviously fall |
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When is the serum soluble transferrin receptor released into the circulation?
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In iron deficiency anaemia but NOT anaemia of chronic disease
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What affects the serum ferritin level?
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Inflammation / tissue injury - this is becuase it's an acute phase protein
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What is hepcidin?
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An important iron regulator molecule. It's a negative regulator (decreased hepcidin -> increased iron)
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What do increased levels of hepcidin result in?
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Hepcidin binds to ferroportin and degrades it.
Lots of hepcidin --> 1. Decreased release of iron from body stores (particularly macrophages) 2. Decreased absorption of iron at the gut |
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What happens to hepcidin levels in inflammation / infection?
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Increased levels in inflammation / infection -> decreased iron (this is beneficial in terms of fighting off the infection becuase lots of bacteria require iron for survival)
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What happens to hepcidin levels in iron deficiency?
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Decreased levels -> try to increase absorption of iron at the gut
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Which form of iron is absorbed across the gut?
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Fe2+ ie ferrous iron
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What channels are involved in transport of iron across gut epithelium?
ie what binds to it on the lumen side then what transports it across on the basolateral membrane? |
DMT1 = on the lumen side
Ferroportin is on the basolateral membrane |
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Why do haem containing dietary sources of iron (meat, dairy, fish) have higher oral bioavailability than the non-haem sources?
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haem sources -> iron is mostly in the Fe2+ form which is more readily transported across
non-haem -> it's in Fe3+ form -> needs to be converted to Fe2+ by ferrireductase on the lumen side of gut epithelium |
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What increases the absorption of non-haem iron?
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Ascorbic acid, citric acid, amino acids, sugar
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What decreases the absorption of non-haem iron at the gut?
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Tannates (ie tea), carbonates, oxalates and phosphates
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What haemoglobin levels are defined as anaemic in both men and women?
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Men: less than 135 g/L
Women: less than 115 g/L |
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What is the normal percentage of reticulocytes on the blood film?
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0.5-2%
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What are the main things you think about with microcytic anaemia?
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Iron deficiency
Thalassemia (An of chronic disease) |
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What sort of anaemia do we get with chronic disease?
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Can be microcytic or normocytic
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In developing countries, what is the main cause of iron deficiency?
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Hookworm infestation -> GI blood loss
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In Australia, what is the most common cause/s of iron deficiency?
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In menstruating women, it's blood loss due to menstruation (Fe deficiency is so common in this population that it's almost considered 'normal')
In older women and men - if you can't explain by obvious blood loss, suspect occult bleed (maybe due to GIT bleed or tumour) |
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What happens to serum transferrin and ferritin in Fe deficiency?
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Transferrin increases
Ferritin decreases |
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How many RBCs are produced in the BM p/second?
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2 million
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What percentage of a RBC is made up by haemoglobin?
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97%
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What are the "two" main types of stem cells in the BM?
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Lymphoid and myeloid
(also have erythroid - these come from myeloid SCs) |
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What is the morphological difference between RBC and reticulocyte?
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Retic is larger. And still contains some RNA -> stains blue
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How long does the maturation of a RBC in the BM take?
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7-10 days
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What stimulates the production of EPO
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Hypoxia in the kidney stimulates EPO production
It then acts back on the BM |
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What happens to your haemoglobin levels during pregnancy ?
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Get a physiological anaemia - because the RBCs are 'diluted out' by the large increase in plasma volume
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What three main factors affect an anaemic person's symptoms?
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1. Speed of onset
2. Patient's general health (if they have a strong heart, the anaemia won't be such a problem) 3. Severity of their anaemia |
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What are the signs of anaemia?
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- Pallor
- Cardiac compensation -> increased HR - Angular stomatitis - Glossitis - Koilonychia |
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What does an increased reticulocyte count indicate?
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The BM is trying to pump out cells rapidly - probably because we're getting peripheral destruction of the cells
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What will happen to LDH, haptoglobin and bilirubin levels with haemolysis?
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LDH and bilirubin will be increased
Haptoglobin is decreased |
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What are the main causes of macrocytic anaemia?
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Megaloblastic -> B12 and/or folate deficiency
Non-megaloblastic -> alcohol abuse, liver disease, myelodysplasia, aplastic anaemia |
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What are the main causes of normocytic anaemia?
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Chronic disease
Haemolysis Acute blood loss Renal disease BM failure (eg post chemo or due to infiltration by tumour) |
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What is megaloblastosis?
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Specific appearance of RBCs in the BM - the nucleus is much LESS delayed than the cytoplasm ie nucleus is granuley in appearance whereas cytoplasm is very mature and hence pale
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What morphological changes do we see on the blood film with megaloblastic anaemia?
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- nucleus-cytoplasm asynchrony (nucleus is immature and hence granuley in appearance, cytoplasm is pale)
- hyper-segmented neutrophils |
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What are hyper-segmented neutrophils on a blood film suggestive of?
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Megaloblastic anaemia
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What is the most common cause of macrocytic anaemia?
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Excess alcohol consumption
This is a non-megaloblastic macrocytosis |
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Why do people with chronic disease have anaemia?
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Things produced by the chronic inflammatory response impair the body's ability to release iron from its stores (hepcidin involved!) - giving them iron supplements won't help because the developing RBCs in the BM don't receive the iron
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Where in our diet do we get Vitamin B12?
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Animal products
True vegans won't get any |
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If you completely cut off your intake of B12, how long could you survive on your liver stores?
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ABout 2-4 years
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What is B12 aka'd?
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Cobalamin
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What is the process by which B12 is absorbed in the gut?
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1. It's released from protein complexes in food by acid-pepsin attack
2. Binds to R proteins in the stomach 3. IF is produced by parietal cells in the stomach - can't bind to B12 in the acidic envt of stomach though 4. Pancreatic enzymes remove R proteins from B12 in the small int -> IF can now bind 5. The B12-IF complexes bind to receptors on microvilli in the TERMINAL ILEUM 6. B12 is transported through the body on proteins called transcobalamins |
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What proteins transport B12 through the blood?
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transcobalamins
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What are the main causes of B12 deficiency?
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- Insufficient intake (rare because don't need heaps - only happens in true vegans)
- Pernicious anaemia - Gastrectomy - Crohn's disease - Pancreatic insufficiency -> won't remove the "R" proteins from B12 in the small int - Some drugs block absorption |
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What is pernicious anaemia?
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Have antibodies directed against parietal cells or IF itself -> decreased levels of IF --> decreased B12 absorption
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What happens to homocysteine levels in B12 deficiency?
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B12 is required to convert homocysteine to methionine
If you have low B12, won't get much of this conversion -> increased homocysteine |
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From where in our diet do we get folate?
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Present in most foods. Highest in liver and yeast. Also high in green vegies and nuts
Bread is now fortified in folate |
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What does folate deficiency do to developing fetus?
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Neural tube defects
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Is B12 destroyed by cooking?
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NO
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If you completely cut off your intake of B12, how long could you survive on your liver stores?
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ABout 2-4 years
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What is B12 aka'd?
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Cobalamin
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What is the process by which B12 is absorbed in the gut?
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1. It's released from protein complexes in food by acid-pepsin attack
2. Binds to R proteins in the stomach 3. IF is produced by parietal cells in the stomach - can't bind to B12 in the acidic envt of stomach though 4. Pancreatic enzymes remove R proteins from B12 in the small int -> IF can now bind 5. The B12-IF complexes bind to receptors on microvilli in the TERMINAL ILEUM 6. B12 is transported through the body on proteins called transcobalamins |
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What proteins transport B12 through the blood?
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transcobalamins
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What are the main causes of B12 deficiency?
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- Insufficient intake (rare because don't need heaps - only happens in true vegans)
- Pernicious anaemia - Gastrectomy - Crohn's disease - Pancreatic insufficiency -> won't remove the "R" proteins from B12 in the small int - Some drugs block absorption |
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What is pernicious anaemia?
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Have antibodies directed against parietal cells or IF itself -> decreased levels of IF --> decreased B12 absorption
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What happens to homocysteine levels in B12 deficiency?
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B12 is required to convert homocysteine to methionine
If you have low B12, won't get much of this conversion -> increased homocysteine |
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From where in our diet do we get folate?
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Present in most foods. Highest in liver and yeast. Also high in green vegies and nuts
Bread is now fortified in folate |
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What does folate deficiency do to developing fetus?
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Neural tube defects
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Is B12 destroyed by cooking?
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NO
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Is folate destroyed by cooking?
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Yes
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If you stop eating folate, how long could you last on your liver stores?
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Only about 3-4 months (shorter than B12 because body consumes folate at higher rate)
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Where is folate absorbed in the gut?
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Proximal jejunum
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What are the causes of folic acid deficiency?
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- Inadequate intake (no leafy greens)
- Increased need eg pregnancy, lactation, malignancy - Increased loss eg dialysis - Malabsorption: Coeliac's, surgical removal of jejunum - Drugs eg methotrexate = anti-folate |
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How do you diagnose pernicious anaemia?
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Anti-IF antibodies
Anti-parietal cell antibodies |
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How does absorption of folate at the gut compare with absorption of B12?
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- folate doesn't require binding of any specific molecules eg IF
- absorption is passive (due to concentration gradients) - ie folate doesn't need to bind to specific receptors on the epithelium |
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Why would you get anaemia with kidney disease?
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Because not properly producing EPO in response to hypoxia
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What causes increased bilirubin?
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Breakdown of haem from Hb
Ie in haemolysis |
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What is haptoglobin?
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It binds to haem in the blood to prevent it from being lost by the kidneys - ie helps to recycle the haem
If RBCs are being broken down really quickly, all the haptoglobin will be used -> low levels |
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What is the Coombs test?
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Looks for antibodies on the surface of the RBC. It's useful if you suspect an autoimmune haemolysis
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WHy do we get spherocytes in autoimmune haemolysis?
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As the RBCs go through the spleen, the RES macros take out chunks of the membrane --> RBCs form sphere shapes because this is the only way they can contain all their contents with the decreased surface membrane
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What happens in the G6PD deficiency?
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RBCs can't generate NADPH to counteract oxidant substances --> cell will get damaged by oxidants
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What does oxidant damage to RBCs do?
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Denatures haemoglobin -> get the formation of Heinz bodies - they adhere to the red cell's membrane and result in destruction of the cell
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