MEH Flashcards
1
Q
energy metabolism is all about producing
A
acetyl-COA - which will be used to produce ATP to be used as energy by cells
2
Q
acetyl- CoA produced by
A
breakdown of fats, alcohol, carbohydrates, protein
3
Q
fats –> acetyl co A
A
fats –> fatty acids + gylcerol
fatty acids used to produce acetyl CoA and ATP via B-oxidation
4
Q
carbhoydrates
A
carbhoydrates –> glucose- 6 P –> glycolysis –> pyruvate –> acetyl CoA –> TCA cycle –> ATP
5
Q
proteins –> acetyl co a
A
protein –> amino acids –> pyruvate –> acetyl CoA–> TCA cycle
6
Q
which metabolites can be used in glucoseneogensis to produce glucose 6-P
A
amino acids
glycerol
lactate
this glucose 6-P will then be used to produce acetyly coA
7
Q
pyyruvate is converted to ….. when low oxygen
A
lactate
lactate can then be used in glucoseneogensis –> glucose -6-P to be used to produced acetyl- CoA and be used in TCA cycle
8
Q
glycolysis
A
glucose –> pyruvate
investment (2ATP) and payback phase (4ATP)
9
Q
key regulator of glycolysis
A
phosphofructokinase
10
Q
citric acid cyle (TCA)
A
acetyl coA (2 carbons) feeds into CAC and combines with oxaloacetate (C4) to produce citrate (C6)
- citrate (loses 2C as CO2 during the cycle) metabolised to produce NADH, GTP and FADH2
- NADH and FADH2 used as reducing power to drive the electron transport chain
11
Q
A
12
Q
electron transport chain and ATP synthesis
A
NADH and FADH2 supply high energy electrons (reducing power)
- electrons pass through series of compelexes pumping H+ ions into the intermembrane space and finally reducing oxygen to form water
- ATP synthases used proton gradient to convert ADP to ATP
13
Q
fatty acid oxidation
A
- fatty acid activation by fatty acyl CoA synthaise
- fatty acid transported into mitochdondria there used carinitine shuffle
- transport inhibited by malonyl CO 9prevents newly synthesised FA from being immediatley transported into mitochondria and oxidsed
- oxidation by B-oxidation pathway
- repeated removal of C2 unit (acetyl CoA–> TCA cycle) and NADh and FADH2 –> ETC
14
Q
ketone bodies
A
- made in the liver mitochdornia from acetykl-CoA
- improtant source in starvation - spare glucose
- brains adapts to use ektone odies if glucose is critically low
15
Q
give an example of when ketones are produced byt he body
A
untreated diabetes , severe dieting and fasting convert acetyl-CoA from fatty acis to ketone bodies
16
Q
high levels of ketons can
A
cause ketoacidosis
- acetone (pear drop smell) on breath
- synthesis controlled by insulin/glucagon
17
Q
lipoproteins
A
18
Q
types of lipoproetiens
A
- Chylomicrons (lipids from our diets) drain into the lymphatic system and enter the the blood stream at the thoracic duct which enters the left subclavian vein
- VLDL- way liver exports fat - circulates fat around then body and gives to tissue that needs it e.g. adipose tissue and as an energy source for muscle
- LDL -depleted VLDL - caused atherosclerotic plaques - very long lived and therefore suscpetive to lipid peroxidation (regonsied by macrophages and these become foam cells which form fatty streak and enbed in smooth muscle)
- HDL- produced by the liver (empty) and travela roudn the body collecting excess fat and take it back to the liver top be processed
19
Q
lipoprotein size
A
20
Q
summary of lipoprotein fucntion
A
21
Q
alcohol oxidation
A
overall can cause
- lactic acidosis
- gout
- hypoglycamia
- fatty liver
22
Q
alcohol metabolism produces
A
NADH which can be used as energy production (ETC)
this process uses up NAD+ which causes lactate to accumulate in blood :
- kidneys abiltiy to excrete uric acid decreased = urate crystals in tissue causing gout
- deficit in glucoseneogensis = hypoglycameia
23
Q
disulifiram
A
alcohol depndent
- inhibits aldheyde dehydrogenase which causes acetaldehyde to huild up = hangover symptoms
24
Q
reactive oxyegn species
A
free radicals:
reactive oxyegn species
- superoxide
- ydrogen peroxide
- hydroxyl radical
reactive nitrogen species
- nitric oxide
- peroxynitirre
25
cellular defences to free radical
glutathione
- needs to be recycles
- requires NADPH (sourced by the pentose ohosphate pahtway)
- people with glucose glucose 6- phosphate dehydrogenase deficiency cant produce suffieicnet amoutn sof NADPH and therefore become suscpetible to oxidative damage to RBC
--\> causing haemolysis and **cataracts**
26
iron
required for oxygen carriers and co-factors in many enzymes
- free iron= toxic to cells
- body has no emchanisms for excreting iron
27
ferric vs ferrous iron
we absorbed both haem iron (Fe2+) and non-haemi (mixture of Fe2+ and Fe3+) in our diet
**Ferric (Fe3+)** must be reduced to **ferrous (Fe2+)** before it can be absorbed from diet
28
haem vs non-haemi iron
absorption occurs in dueodenuma nd upper jejunum (haem iron best source)
spme foods foritfied with iron e.g. cereal
29
dietry absorption of iron
haem iron absorbed dierctly
non-haem needs to be reduced from fe3+ to Fe2+ and then absorbed by the cell
stored as ferritin or exproted intot he blood via **ferroportin**
**Fe2+ is then oxidised to Fe3+ via hephaestin**
**transported around the body via Transferrin**
30
hepicidin
produced by the liver
inhibits ferroportin
- anaemia of chronic disease shows increased hepcidin --\> microcytic anaemia due to low iron
31
the adrenal gland
- cushings disease
- addisons disease
- hypothryoidism se..g hashimotos
hyperthyroidsm- graves
32
cushins syndrome
external and endogenous causes
external - prescribed glucocorticosterois
endogenous causes
* benign pituitary adneoma secreting ACTH - cushins disease
* excess cortisol produce dby adrenal tumour- adrenal cushins
* non-pituitary adrenal tuimours producing ACTs e.g. small cell lung cancer
33
34
physiological life cycle of RBC
120 days
RES- spleen and liver
35
* Symptoms: shortness of breath, tiredness, palpitations, headache, cardiac failure
* Signs: pallor, tachycardia, tachypnoea, hypotension
* Other signs and symptoms specifically associated with the cause of anaemia
36
possible causes of anaemia think
bone marrow
peripheral red bloo cells
removal
37
what can you use to differentiate cause of anemia
reticulocyte count
low= bone marrow issue
high= peripheral problem
38
reticulocytes
39
evalutation of anaemia
40
high reticulocytes usually causes
macrocytic cells
41
cause of macrocytic anaemia
* Vitamin B12 deficiency
* Folate deficiency
* Myelodysplasia
* Liver disease
* Hypothyroidism
• Alcohol
42
normocytic anameia causes
43
microcytic anaemia causes
44
is there an appropriate reticulocyte response? YES
is there haemolyis? cause
is there evidence of bleeding?
45
in patients where there is an appropriate reticulocyte response what is expected
LDH released when RBC breakdown
46
evidence of bleeding?
- anti-inflammaotries causing gastric bleed etc
- heavy epriods
47
haemolytic anaemia
– within blood vessels (intravascular haemolysis)
– or in the spleen or wider RES (extravascular haemolysis)
Red cells normal lifespan ~120 days
48
haemolytic anaemia results in
* Symptoms of anaemia – severity worse if Hb v low or if an acute fall in
* Accumulation of bilirubin leading to jaundice and associated risk of complications such as pigment gallstones.Hb rather than in chronic disease
* Overworking of the red pulp leading to splenomegaly
* Massive sudden haemolysis (as can happen in an incompatible blood transfusion) can cause cardiac arrest due to:
* Lack of oxygen delivery to tissues
* Hyperkalaemia as a result of release of intracellular contents
49
inherited defects in red cell membrane structures
50
acuired cauaed of defects in red cell membrane structure
will see schistocytes (red blood cell fragements)
51
defects in red cell metabolism
52
defects in Hb synthesis
53
thalassaemia
reduced rate of synthesis of normal α- OR ß- globin chains (the α- and ß- thalassaemias)
54
Sickle cell disease:
synthesis of an abnormal haemoglobin
55
removal of excess cells by RES
* The spleen and other tissues of RES removes damaged or defective red cells
* It will do this in many of the causes of anaemia already covered eg membrane disorders, enzyme disorders, haemoglobin disorders
* In Haemolytic anaemias, (Session 5) red cells are destroyed more quickly as they are abnormal or damaged
* This can occur within the blood vessels intravascular or outside (within the RES macrophages in spleen. Liver, bone marrow) extravascular
56
eg Autoimmune Haemolytic anaemia
* In this condition autoantibodies (ie Immunoglobulin -Ig – protein produced by own B lymphocytes) bind to the red cell membrane proteins
* Cells in the RES recognise part of the antibody, attach to it and remove it and the red cell from the circulation
* Broadly classified as
* – warm autoimmune haemolytic anaemia (IgG, maximally active at 370C) – cold autoimmune haemolytic anaemia (IgM, maximally active at 40C)
* Causes can be infections (eg chest infections in children causing the cold form) or cancers of the lymphoid system (eg B cell lymphoma)
* The spleen recognises the red cell as ‘abnormal’ and removes it .. So reducing the life span
57
Haemolytic anaemia
• More on the subtypes, investigation and treatment of Haemolytic anaemia will be covered in more detail later in the course
• Some key laboratory features:
– increased reticulocytes (as the marrow tries to compensate)
– raised bilirubin (breakdown of Haem)
– raised LDH (red cells rich in this enzyme)
58
Haematocrit/Packed Cell volume (PCV)
* Proportion of blood that is made up of RBC – Centrifuged blood allows visualisation
* Used to assess anaemia but more often polycythaemia
– Diagnosis and treatment
59
Haemoglobin
Reference ranges vary between labs but generally
\<135g/L adult men
\< 115g/L adult women
\<110g/L children (3/12 – puberty)
\<150g/L newborns
* Haemoglobin concentration in the blood i.e. amount of Hb mass/plasma volume
* Acute bleed Dehydration
* In vitro haemolysis will reduce Hb
60
Red Cell Count (RCC) (x1012/L)
Number of RBC in given volume of blood (single cell column of blood passing through a detector)
Used for assessment of anaemia
* Microcytic anaemia, RCC is
* reduced in iron deficiency anaemia
* increased in thalassemia trait
61
Mean Cell Volume (MCV) (fL)
* Mean size of RBC, measured using the amount of light scattered as they pass in a single file past a laser.
* The most important parameter used to screen the cause of anaemia
62
Red Cell Distribution Width (RDW)
Variation in size of the RBC
* If increased = **anisocytosis**
* Used to help assess cause of anaemia
* Increased in iron deficiency (the first parameter to rise as iron stores fall)
* Usually normal in thalassaemiatrait.
* Increased following transfusion
63
Mean Cell Haemoglobin (MCH) (pg)
* Average measure of the amount of Hb in each RBC (e.g. Hb/RCC)
* Used in assessment of anaemia
• Usually
– reduced in iron deficiency but
– normal or increased in macrocytic anaemias
64
Mean Cell Haemoglobin Concentration (MCHC) (g/L)
• Mean concentration of Hb in RBC (Hb/MCV x RCC)
• One of least useful parameters:
– usually reduced if hypochromia present – increased if spherocytosis.
• Most useful in laboratory in the identification of cold agglutinins (e.g. viral/ mycoplasma infections etc.)
65
Reticulocyte Count (x109/L)
• Measurement of the number of young erythrocytes
## Footnote
**• Identified using size and RNA content.**
66
reticulocytes identified using
size and RNA content
67
Vitamin B12 and/or folate deficiency causes
causes a deficiency in building blocks for DNA synthesis
Red cells become enlarged ie this is a form of a macrocytic anaemia
68
vitamin B12 absorption
B12 from food (meat, fish, eggs and cheese)
- binds to Haptocorrin (produced by salivary glands)
- in the stomach HCL is secreted and cause B12 to bind to intrinsic factor (both produced by parietal cells)
**- absorbed in the terminal ileum**
69
Causes of low Vit B12
70
Folate
Folate present in most foods, yeast, liver and leafy greens especially rich source
5mg stores for about 3-4 months
• Absorptionoccursintheduodenumandjejunum
71
Deficiency of Folate could result from:
72
The Vit B12/folate link
* Both B12 and folate play a role in converting homocysteine to methionine and the 2 vitamins are dependent on one another to do this.
* Vitamin B12 is responsible for reactivating folic acid, back into tetrahydrofolate, the form of folic acid which the body can use.
* so low B12 causes a functional folate deficiency
* THF is essential for: serine-glycine conversion, histidine catabolism, purine synthesis, and most importantly, thymidylate synthesis which is needed throughout the body for DNA synthesis
* Vitamin B12 needs folic acid to convert homocysteine to methionine. MTHF gives off its methyl group to vitamin B12 (cobalamin), which becomes methylcobalamin. At the same time, the MTHF folic acid is converted back into its bioactive form, tetrahydrofolate
* Methylcobalamin then gives off its methyl group to homocysteine, to create methionine
* Methionine is converted to S-adenosyl methionine (SAM) – very important in the production of various neurotransmitters and for DNA methylation.
73
Why does Vit B12 and folate deficiency cause a megaloblastic anaemia?
So....both folate and Vit B12 deficiency ultimately lead to thymidylate deficiency
* In the absence of **thymine**, **uracil** is incorporated into DNA instead
* **DNA repair enzymes detect the error and DNA strands are destroyed**
* This causes asynchronous maturation between the nucleus and the cytoplasm.
* The nucleus (lacking DNA) does not fully mature,
* The cytoplasm ,in which RNA production and haemoglobin synthesis continues, matures at the normal rate
74
74
Deficiency in building blocks for DNA synthesis lead to anaemia – Vitamin B12 and/or folate deficiency
The peripheral blood film shows megaloblastic features:
* macrocytic red cells
* anisopoikilocytosis with tear drops
* hypersegmented neutrophils
* Can see white cell precursors also
75
Deficiency in building blocks for DNA synthesis due to Vit B12 or folate deficiency lead to
neurological disease
**• Vitamin B12** (not folate) deficiency is also associated with neurological disease – focal demyelination affecting the spinal cord, peripheral nerves and optic nerves.
**• Folate deficiency** in pregnancy can cause neural tube defects
76
Investigation of megaloblastic anaemia
77
treatment for folate deficiency
oral folic acid
78
treatment for B12 deficiency
* Pernicious anaemia: Hydroxycobalamine (intramuscular) for life
* Beware hypokalaemia (low potassium) !
* Other cause: oral cyanocobalamine
Transfusion in patients with Vit B12 deficiency can cause high output cardiac failure
79
White cells
* Neutrophils
* Lymphocytes (B/T/ NK)
* Monocytes
* Eosnophils
* Basophils
Raised mainly in reactive conditions but can be associated with underlying haematological disorders-but very rare
80
macrophages
81
interleukin 6
82
* Janus kinase
* Tyrosine kinases which increase proliferation and survival of haemotopoetic precurosrs
83
**Polycythemia vera**
(pol-e-sy-THEE-me-uh VEER-uh) is a type of blood cancer. It causes your bone marrow to make too many red blood cells. These excess cells thicken your blood, slowing its flow, which may cause serious problems, such as blood clots.
84
microangiopathic haemolytic anaemia
85
anisocytosis
86
imatinib
87
* Iron is not made available for the bone marrow
* Hepcidin cause the ferroprotein to be internalised and degraded
* **In chronic diseases, high hepcidin production inhibits iron release from macrophages and intestinal absorption of iron. This consequently induces an anaemic condition. The interaction between hepcidin and ferroprotein determines the plasma iron transport.**
88
**DIC**
**Disseminated intravascular coagulation** (**DIC**) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts of the body.
* Secondary to other disorders- uncontrolled coagulopathy
89
* Sequestration and phagocytosis of old and abnormal rbc
90
glossitis
91
teardrop cells
92
**Howell**-**Jolly bodies** are remnants of RBC nuclei that are normally removed by the spleen. Thus, they are seen in patients who have undergone splenectomy (as in this case) or who have functional asplenia (eg, from **sickle cell** disease). Target **cells** (arrows) are another consequence of splenectomy.
93
* Aspirin only if she was over 18
* Causes reyes syndrome in children
* Liver and brain damage
* Wouldn’t use warfarin because its hard to get the dosage right (anticoagulant not an antiplatelet)
94
immature RBC
reticulocyte
95
kidney
* Produced when blood oxygen is deficient (hypoxia)
* Promotes RBC progenitor survival in the bone marrow
96
phlebotomy
97
Disulphide bond in a proteinc can ebe formed btween two residues of which amino acid?
Cysteine
98
* Glucagon
99
decreased activity
100
* Pentose phosphate cycle
101
* They involve the synthesis of larger molecules from intermediary metabolites
102
* Kilojoule
103
B6
104
* Accumulation of acetaldehyde
105
alcohol dependence
106
Stimulates fatty acid synthesis via dephosphorylation of acetyl-CoA carboxylase
107
starch
108
enter glycolysis
109
* NADH
110
* NAPQI
111
* Lipoprotein lipase
112
* Glycolysis
113
* Alanine aminotransferase
114
* C (18:3- 3 means 3 double bonds)
115
* Calcitonin
Parathyroid hormone is secreted by the parathyroid gland
116
* T3 and T4 are produced by the
* thyroid gland follicular cells
* Arranged in follicles full of colloid
117
Parafollicular cells (C cells)
located in the space between thyroid follicles
* calcitonin
118
thyroid hormone synthesis
119
* hypopituitarism resulting in ACTH deficiency
120
-ve
121
* large hands and feet
122
* bromocriptine
* prolactinomas are well controlled by medication and does not require surgery
123
* galactorrhea
124
insulin secretion would increase
125
supraoptic nucleus
126
arcuate nucleus repsonsible for
appetite
127
* osteoclasts
128
129
* peptide hormone
130
steroid hormone
131
alpha cells- glucagon
132
* increased sunlight exposure
133
134
ketoacidosis
135
paracrine
136
E
137
* Decreased maternal utlisisation of glucose
138
ghrelin
