The Liver As A Storage Organ Flashcards
What function does the liver have?
What functions does the liver perform?
Carbohydrate metabolism
Fat metabolism
Protein metabolism
Hormone metabolism
Toxin/Drug metabolism and excretion
Storage
Bilirubin metabolism and excret
How is iron transported?
Through transferrin
How is iron used in the body?
- Bone marrow: circulating erythrocytes (heamoglobin)
- Muscle (myoglobin)
Where is iron stored?
- In the liver parenchyma
- In the reticuloendothelial macrophages
How is Iron lost?
- Sloughed mucosal cells (loss of tissue cells)
- Desquamation (skin sheds)
- Mestruation
- Other blood loss
What is the structure of ferritin?
- Large spherical protein consisting of 24 no-covalently linked subunits
- Core contains up to 5000 atoms of iron (high conc)
Where is ferritin found?
- In the cytoplasm of cells but can also be found in the serum (blood)
What does the concentration of ferritin tell us?
Directly proportional to the total iron stores in the body
- therefore we can use it if we think a patient has an iron deficiency
What are some excess iron storage disorders due to ferritin excess?
- Hereditary haemochromatosis
- Haemolytic anaemia
- Sideroblastic anaemia
- Multiple blood transfusions
- Iron replacement therapy
What are some non-iron overload conditions that cause ferritin excess?
- Liver disease
- Some malignancies
- Significant tissue destruction
- Acute phase response:
Inflammation
Infection
Autoimmune disorders
What causes low ferritin deficiency?
Iron deficiency
- This can result in anaemia
- Ferritin less than 20 ug/L indicates depletion
- Ferritin less than 12 ug/L suggests a complete absence of stored iron
What is the RDA and AI?
RDA - Recommended daily allowance
AI - Adequate intake
How do vitamins benefit the body?
- Gene activators
- Free-radical scavengers
- Coenzymes or cofactors in metabolic reactions
What can excessive vitamin ingestion lead to?
Can result in toxicity
What is the difference between water and fat soluble vitamins in terms of movement?
Water soluble vitamins pass more readily through the body, therefore, require more regular intake than fat soluble vitamins
- So fat soluble vitamins are much better at storage
Is vitamin A a fat soluble or water soluble vitamin?
Fat soluble
What can we eat to gain Vitamin A?
Vertebrates ingest retinal directly from meat or produce retinal from carotenes (found in fruit and veg)
What are the functions of vitamin A?
- It is important for sight and vision: Used to form rhodopsin in the rod cells in the retina
- Reproduction: Spermatogenesis in male
Prevention of foetal resorption of female - Growth
- Stabilisation of cellular membranes
How much vitamin A do we need to intake each day?
0.6 mg/day in men, 0.7 mg/day in women
What happens when we have a vitamin A deficiency?
- Rare in affluent countries as vitamin A levels drop only when liver stores are severely depleted.
- Deficiency may occur due to fat malabsorption
What are the clinical features to look out for with a Vitamin A deficiency?
Clinical Features:
Night blindness
Xeropthalmia
Blindness
What are the symptoms of vitamin A in excess in acute cases?
Abdominal pain, nausea and vomiting
Severe headaches, dizziness, sluggishness and irritability
Desquamation of the skin (skin peeling)
What are the symptoms of vitamin A in excess in chronic cases?
Joint and bone pain
Hair loss, dryness of the lips
Anorexia
Weight loss and hepatomegaly (enlarged liver)
What is carotenemia and what causes it?
Reversible yellowing of the skin
Does not cause toxicity
Caused by Vitamin A excess
What are the functions of Vitamin D?
- Increased intestinal absorption of calcium
- Resorption and formation of bone
- Reduced renal excretion of calcium
What happens when there is a vitamin D deficiency?
Demineralisation of bone:
- Rickets in children
- Osteomalacia in adults
Where can we get vitamin D from?
Sunlight, fish, meat, supplements
Where is vitamin E stored?
- Non-adipose cells such as liver and plasma: labile and fixed pool
- Adipose cells: fixed pool
What is the function of vitamin E?
Important antioxidant
What are the vitamin E requirements?
4 mg/day in men
3 mg/day in women
Where can you get vitamin E from?
almonds, hazelnuts, oil, spinach, carrots, avocado
What is a vitamin E deficiency caused by?
- Fat malabsorption (e.g. cystic fibrosis)
- Premature infants
- Rare congenital defects in fat metabolism e.g. abetalipoproteinaemia.
What are the clinical manifestations of a vitamin E deficiency?
Haemolytic anaemia
Myopathy
Retinopathy
Ataxia
Neuropathy
What happens when we have vitamin E in excess?
relatively safe
How is vitamin K taken up?
Vitamin K is rapidly taken up by the liver but then is transferred to very low-density lipoproteins and low density lipoproteins which carry it into the plasma.
What are some sources of vitamin K?
- Vitamin K1 (phylloquinone)
Synthesized by plants and present in food - Vitamin K2 (menaquinone)
Synthesized in humans by intestinal bacteria - Synthetic vitamin K’s:
K3 (menadione)
K4 (menadiol)
What are the functions of vitamin K?
- Vitamin K is responsible for the activation of some blood clotting factors.
- Necessary for liver synthesis of plasma clotting factors II, VII, IX and X.
- Can be assessed by measuring prothrombin time.
What happens when we have a deficiency of vitamin K?
- Haemorrhagic disease of the newborn:
Vitamin K injection given to newborn babies - Rare in adults, unless on warfarin.
What happens when we have an excess of vitamin K?
- K1 is relatively safe
- Synthetic forms are more toxic
- Can result in oxidative damage, red cell fragility and formation of methaemoglobin.
Is vitamin K a fat soluble or water soluble vitamin?
fat soluble
Is vitamin E a fat soluble or water soluble vitamin?
fat soluble
Is vitamin D a fat soluble or water soluble vitamin?
fat soluble
Is vitamin C a fat soluble or water soluble vitamin?
water soluble
Is vitamin B12 a fat soluble or water soluble vitamin?
water soluble
Is folate a fat soluble or water soluble vitamin?
water soluble
Where is vitamin C found?
fresh fruit and veg
How much vitamin C does an adult need?
40mg/day (a lot more than fat soluble vitamins)
What are the functions of vitamin C?
- Collagen synthesis
- Antioxidant
- Iron absorption
What happens when there is a vitamin C deficiency?
Deficiency – Scurvy
- Easy bruising and bleeding
- Teeth and gum disease
- Hair loss
What happens to improve vitamin C deficiency?
- Treatment with vitamin C improves symptoms quickly
- Joint pain gone within 48 hours
- Full recovery within two weeks
What happens when there is an excess of vitamin C?
- Doses > 1g/day can cause GI side effects
- No evidence that increased vitamin C reduces the incidence or duration of colds.
What are the two forms of Vitamin B12?
- Methylcobalamin
- 5-deoxyadenosylcobalamin
How is vitamin B12 absorbed by the body?
- Released from food by acid and enzymes in the stomach
- Binds to R protein to protect it from stomach acid
- Released from R proteins by pancreatic polypeptide.
- Intrinsic factor (IF) produced by the stomach needed for absorption.
Where is vitamin B12 absorbed and stored?
IF-B12 complex absorbed in the terminal ileum.
B12 is stored in the liver.
What are the causes of a B12 deficiency?
- Pernicious anaemia: autoimmune destruction of IF-producing cells in stomach so can’t absorb B12
- Malabsorption: lack of stomach acid, pancreatic disease, small bowel disease.
- Veganism
What are the symptoms of a B12 deficiency?
- Macrocytic anaemia
- Peripheral neuropathy in prolonged deficiency
What foods have vitamin B12 in them?
meat, fish, eggs, dairy
Where is folate found?
Many foods are fortified with folic acid
Why would someone need higher levels of folic acid?
if they were pregnant
What are the functions of folate?
Functions as a coenzyme in methylation reactions, DNA synthesis, synthesis of methionine from homocysteine
What are the causes of a folate deficiency?
- Malabsorption
- Drugs that interfere with folic acid metabolism (anticonvulsants, methotrexate)
- Disease states that increase cell turnover (e.g. leukaemia, haemolytic anaemia, psoriasis)
What are the symptoms of a folate deficiency?
- High homocysteine levels
- Macrocytic anaemia
- Foetal development abnormalities (neural tube defects)
What are the 2 coagulation cascades for clotting?
Intrinsic pathway and extrinsic pathway
What number clotting factors are needed for the intrinsic pathway?
XII, XI, IX, VIII
What number clotting factors are needed for the extrinsic pathway?
VII activates it by coming in to contact with tissue factor which initiates a cascade which ultimately results in fibrin clot formation
Where are clotting factors I (Fibrinogen), II (Prothrombin), IV ,V, VI, VII produced?
In the liver
How do we measure how well clotting pathways are working?
See how long it takes for someones blood to clot
What are the two ways to measure how well clotting pathways are working?
- Prothrombin time (PT) (extrinsic pathway) also called…
International normalised ratio (INR) - Normally done on ppl who take warfarin as a regular check - Activated partial thromboplastin time (aPTT) (intrinsic pathway)
What would a prolonged PT test indicate?
- A prolonged PT may indicate a deficiency in the synthetic capacity of the liver.
- Prolonged PT is not specific for liver disease can be due to:
DIC
Severe GI bleeding
Some drugs
Vitamin K deficiency
