MEH Flashcards
(303 cards)
1
Q
What is the definition of metabolism?
A
The process is which food is broken down into energy and raw materials to be used for repair, growth and activity of the tissues to sustain life.
2
Q
What is a catabolic pathway?
A
Breaking down larger molecules into smaller ones, releasing energy.
It is an oxidative process, releasing hydrogen atoms, generating reducing power.
3
Q
What is an anabolic pathway?
A
The synthesis of larger molecules from smaller molecules, requiring energy.
It is a reductive process, using hydrogen atoms.
4
Q
What are exergonic and endergonic reactions?
A
Exergonic - releases energy.
Endergonic - requires energy.
5
Q
What are the characteristics of exergonic reactions?
A
They can occur spontaneously.
They are -DeltaG.
They release chemical bond energy.
They are seen in catabolic reactions.
6
Q
What type of reactions releases chemical bond energy, and what are some characteristics?
A
Oxidation - the removal of electrons or hydrogen atoms.
They are accompanied by reduction reactions - the gain of electrons or hydrogen atoms.
7
Q
What are the 3 types of hydrogen carrier molecules, in their oxidised form?
A
NAD+.
NADP+.
FAD.
8
Q
What are H-carrier molecules synthesised from, how are they converted between oxidised and reduced form, and what are they used for?
A
They are synthesised from vitamins.
They are converted between the two states through the loss or gain of 2 hydrogen atoms.
They are used for biosynthesis or for ATP production.
9
Q
How much energy is released from the breaking of the gamma-phosphate bond of an ATP molecule?
A
31kJ/mole.
10
Q
How much ATP is within the human body, and how is this sufficient for energy demands?
A
250g.
It is not a store for energy: it is a way of constantly turning over energy - a carrier of energy.
11
Q
What are some high-energy signals and what do they activate?
A
ATP, NADH, NADPH, FADH.
They activate anabolic pathways.
12
Q
What are some low-energy signals, and what do they activate?
A
ADP, AMP, NAD+, NADP+, FAD.
They activate catabolic pathways.
13
Q
What is the molecule used to store energy when rapidly required, and how is it synthesised?
A
Creatine phosphate.
Creatine and ATP are catalysed by creatine kinase to form creatine phosphate and ADP.
It can be used in the first few seconds of exercise, once the ATP stores are depleted.
14
Q
What is creatine kinase a marker of?
A
It is a marker of muscle damage.
It used to be used to signify MI’s but now use troponins.
15
Q
What is creatinine a marker of, and what do different levels mean?
A
Creatinine is a marker of kidney function.
It is a breakdown product of creatine and is proportional to muscle mass, produced at a constant rate.
Elevated levels signify kidney function reduction.
16
Q
What is tyrosine synthesised from, within the body?
A
The amino acid phenylalanine.
17
Q
What is cysteine synthesised from, in the body?
A
The amino acid methionine.
18
Q
What is refeeding syndrome, and what is the key abnormality caused by it?
A
It is where a patient who is starved or inadequately nourished is fed energy rich foods, which leads to rapidly increased plasma glucose levels, resulting in glycogen, fat and protein synthesis.
These processes utilise phosphate, magnesium and potassium, resulting in electrolyte abnormalities.
The key abnormality is hypophosphataemia.
19
Q
What are the risk factors or refeeding syndrome?
A
A BMI < 16.
Unintentional weight loss of greater than 15% within 3-6 months.
10 days or more without (or very little) nutritional intake.
20
Q
How should someone at risk of refeeding syndrome be re-fed?
A
5-10 kcal/ kg/ day.
It should be gradually raised to the requirements within the week.
21
Q
What are the 4 stages, and their features, of catabolism?
A
Stage 1 - breakdown of dietary macronutrients for absorption, occurring in the GI tract.
Stage 2 - glycolysis, breaking down the metabolic intermediates, producing reducing power and 2 molecules of ATP, in the cytosol.
Stage 3 - TCA cycle, producing reducing power and GTP, occurring in the mitochondria.
Stage 4 - oxidative phosphorylation, utilising the reducing power for ATP production, occurring in the mitochondria.
22
Q
What is the minimum requirement of glucose per day?
A
180g:
- 40g/24 hours from the RBCs, neutrophils, innermost cells of the kidney medulla, and the lens of the eye.
- 140g/24 hours from the brain.
23
Q
Which glycosidic bonds do pancreatic amylase and isomaltase break down?
A
Pancreatic amylase = alpha-1,4 bonds.
Isomaltase = alpha-1,6 bonds.
24
Q
What are the 3 types of lactose intolerance?
A
Primary lactase deficiency = absence of lactase persistence allele.
Secondary lactase deficiency = caused by injury to the small intestine.
Congenital lactase deficiency = autosomal recessive defect in the lactase gene.
25
Where are the different GLUT transports found throughout the body?
GLUT 1 = blood-brain barrier and RBCs.
GLUT 2 = small intestine, pancreatic beta cells, kidney and liver.
GLUT 3 = neurons and placenta.
GLUT 4 = adipose and skeletal muscle.
GLUT 5 = spermatozoa and intestine.
They utilise passive transport, unlike SGLTs.
26
What are the functions of glycolysis?
2 NADH produced.
2 ATP produced.
Metabolic intermediates.
27
What are the 2 main rate-determining enzymes of glycolysis, and why are there so many enzymes?
Phosphofructokinase and hexokinase (glucokinase in the liver).
There are so many as:
- There is better control.
- Better versatility; can produce useful intermediates.
- Efficient energy conservation.
- Chemistry is easier.
28
What are some important intermediates of glycolysis?
2,3-bisphosphoglycerate - regulates affinity for oxygen of red blood cells.
Glycerol phosphate - important for triglyceride and phospholipid synthesis.
29
What allosteric regulators inhibit and stimulate phosphofructokinase?
Inhibitors:
- ATP.
- Citrate.
Stimulators:
- AMP/ ADP.
- Fructose-2,6-bisphosphate.
30
How is hexokinase (glucokinase in the liver) regulated?
Both (and phosphofructokinase) by insulin: glucagon ratio - insulin stimulates, glucagon inhibits.
ONLY hexokinase inhibited by the product of its reaction - glucose-6-phosphate.
31
When is lactate produced?
In pathological situations, such as in shock and congestive heart failure.
Naturally, without major exercise.
Increased with strenuous exercise.
32
What are the two enzymes involved in fructose metabolism, and what are their reactants and products?
Fructokinase - converts fructose into fructose-1-P.
Aldolase - converts fructose-1-P into glyceraldehyde-3-P.
33
What are the 3 enzymes involved in galactose metabolism, and what are the reactants and products?
Galactokinase - converts galactose into galactose-1-phosphate.
Uridyl transferase - converts galactose-1-phosphate into glucose-1-phosphate.
UPD-galactose epimerase - converts galactose-1-phosphate into UDP-galactose.
34
What organs does galactose-1-phosphate affect and what enzyme is in deficiency for it to accumulate with?
The brain, liver and kidneys.
Associated with galactose-1-phosphate uridyl transferase enzyme.
35
When would galactose be converted to galactitol, what is this done by, and what is the outcome?
It occurs when there is an accumulation of galactose, seen with a galactokinase or uridyl transferase deficiency.
It is converted by aldose reductase.
Accumulation in galactitol causes cataracts.
36
What is acetyl-CoA derived from?
Vitamins - particularly vitamin B’s.
37
What is pyruvate dehydrogenase formed from, and what is it sensitive to?
It is a multi-enzyme (5) complex.
It is sensitive to vitamin B1 deficiency.
38
What is the central pathway in catabolism of sugars, fatty acids, ketone bodies, amino acids and alcohol?
TCA cycle.
39
Where is the energy for ATP synthesis coming from?
The dissipation of energy from high-energy electrons, as they travel across the electron transport chain, supplied by the NADH and FADH2.
40
What are the 4 ‘layers’ of a mitochondrion?
The outer mitochondrial membrane.
The inter membrane space.
The inner mitochondrial membrane.
The mitochondrial matrix.
41
How many protons do each of the proton translocating complexes move, per 2 electrons?
PTC1 = 4 hydrogen ions.
PTC3 = 4 hydrogen ions.
PTC4 = 2 hydrogen ions.
42
What percentage of energy dissipated from the high energy electrons is used to move the hydrogen ions, and what happens to the rest of the energy?
30% of the energy is required to move the hydrogen ions across the mitochondrial membrane, with the rest being dissipated as heat.
43
What is the proton motive force?
An electrochemical gradient of positive charged hydrogen ions, generated across the inner mitochondrial membrane.
44
How is the proton motive force used to generate ATP?
H+ ions are impermeable to the inner mitochondrial membrane, and so they are transported down the electrochemical gradient through the ATP synthase.
The energy from movement of these protons drives the synthesis of ATP, from ADP.
45
What are some examples of electron transport inhibitors and oxidative phosphorylation uncouplers, what do they do?
Inhibitors = cyanide and carbon monoxide - prevents the movement of electrons through the ETC.
Uncouplers = fatty acids, dinitrophenol, dinitrocresol and UCP1 - dissipate the PMF as heat.
46
How does brown adipose tissue work to increase the temperature of new born infants?
In response to cold, noradrenaline is released which activates lipase to release fatty acids from TAGs.
These fatty acids undergo beta-oxidation, giving reducing power to FADH2 and NADH.
The fatty acids also activate UCP1, which is present in brown adipose.
UCP1 facilitates the movement of H+ ions back across the inner mitochondrial membrane, dissipating the PMF as heat.
47
What is the net yield of ATP from 1 glucose molecule?
32 moles.
48
What are the 3 lipid molecules used as fuel molecules?
Fatty acids.
Glycerol.
Ketone bodies.
49
What are the two products of beta-oxidation, and what occurs with them?
Shorter fatty acid chain - can enter beta-oxidation again or be stored as TAG.
Acetyl-CoA - enters the TCA cycle.
50
What are the characteristics of ketone bodies?
They are acidic.
They are soluble.
They can be used as an alternative fuel to glucose.
They can be used by peripheral tissues.
They are converted into acetyl-CoA when in excess.
51
Which ketone body is not a biological fuel?
Acetone.
52
How can acetyl-CoA be converted to ketone bodies, and what is the other final product from the intermediate (how does it get there)?
Acetyl-CoA is converted to HMG-CoA by HMG-CoA synthase.
HMG-CoA synthase is then converted to acetoacetate by HMG-CoA lyase (which can then be converted into acetate or beta-hydroxybutyrate).
Alternatively, HMG-CoA can be converted into cholesterol by HMG-CoA reductase.
53
How much energy does a gram of fat, alcohol, protein and carbohydrate have in it?
Fat = 37kJ/g.
Alcohol = 29kJ/g.
Protein = 17kJ/g.
Carbohydrate = 17kJ/g.
54
What is the recommended limit of alcohol consumption per week for men and women?
14 units per week, spread over at least 3 days.
It is the same for both men and women.
55
What is the damage done when a ROS reacts with a base or with a sugar?
With a base, mutation and mispairing can occur.
With a sugar, a strand break and mutation on repair may occur.
56
What are the 3 types of nitric oxide synthase (NOS) enzymes, and what are their functions?
iNOS - (inducible) used in the respiratory burst.
eNOS - endothelial signalling.
nNOS - neuronal signalling.
57
How does glutathione act as an antioxidant, and what is required for it to function?
The thiol group on the cysteine residue donates an electron, and combines with an adjacent GSH to form GSSG.
This reaction is catalysed by glutathione peroxidase, which requires selenium to work.
58
How is GSSG returned to glutathione?
Glutathione reductase utilises the H+ and e- from NADPH, to form two glutathione molecules.
59
How is paracetamol removed at therapeutic levels?
Conjugated to glucuronide or sulphate.
60
What is creatinine a breakdown product of?
Creatine and creatine phosphate in the muscle.
It is usually produced at a constant rate.
61
What 3 amino acids are conditionally required in children and in pregnant women?
Arginine, tyrosine and cysteine.
62
What is required for aminotransferases to function?
Pyridoxal phosphate, a derivative of vitamin B6.
63
What do ALT and AST do?
ALT = convert alanine and alpha-ketoglutarate into pyruvate and glutamate, respectively.
AST = convert aspartate and alpha-ketoglutarate into oxaloacetate and glutamate, respectively.
64
What enzymes can deaminate amino acids?
Amino acid oxidases.
Glutaminase.
Glutamate dehydrogenase.
65
Broadly speaking, what are all of the defects in the urea cycle?
They are all genetic disorders that cause a partial loss of enzyme function.
Complete loss of one of the 5 enzymes would be lethal.
66
What does the severity of urea cycle defects depend on?
The nature of the defective enzyme.
The amount of protein eaten.
67
Describe how glutamine transports the amino acid amine group for disposal.
- Ammonia is combines with glutamate to form glutamine.
- This reaction is catalysed by glutamine synthetase.
- Glutamine is cleaved by glutaminase to release the ammonia for the urea cycle in the liver or excretion via the kidney.
68
Describe how alanine transports the amino acid amine group for disposal.
Amine groups are transferred to glutamate by transamination.
Pyruvate is then transaminated by glutamate to form alanine.
Alanine is transported in the blood to the liver where pyruvate is formed again via transamination.
The amine group enters the urea cycle for disposal.
Pyruvate is converted to glucose via gluconeogenesis for use by the tissues.
69
What is the deficiency in phenylketonuria, and what is the treatment?
It is an autosomal recessive defect in the phenylalanine hydroxylase enzyme.
It is treated by have a low phenylalanine with enriched tyrosine diet, with no artificial sweeteners and a low protein diet.
70
What are the symptoms of phenylketonuria?
Musty urine smell - phenylketones building up in the urine.
Microcephaly.
Seizures.
Hypopigmentation.
Developmental delay.
Intellectual disability.
71
What is the defect in homocystinuria, and what is the treatment?
It is an autosomal recessive defect in the cystathionine beta-synthase
Treatment is a low methionine diet (avoid milk, fish, meat, cheese, etc.). Cysteine, vitamins B6 and B12, and folate supplements.
72
What glycosidic bonds are linked for the glycogen chains and branches, and what is the ratio of them?
Chains = alpha-1,4.
Branches = alpha-1,6.
A 1:10 ratio in favour of chains.
73
What is McArdles disease?
It is a defect in the glycogen phosphorylase enzyme, leading to an excess of glycogen in the muscle and liver.
74
What are the 3 key enzymes of gluconeogensis?
Main 2 are PEPCK and fructose-1,6-bisphosphate.
The other is glucose-6-phosphatase.
75
How are TAGs stored?
In anhydrous form in adipocytes.
They are a high energy store.
Adipocytes can increase in size by about 4 fold before increase in total number of cells (of which is irreversible).
76
Outline the steps of fatty acid synthesis (lipogenesis).
In the liver, glucose is converted to pyruvate via glycolysis.
Pyruvate is converted to acetyl-CoA in the mitochondria (pyruvate dehydrogenase) and enters the cytoplasm.
Acetyl-CoA is converted to malonyl-CoA via acetyl-coA carboxylase.
Malonlyl-CoA is added to fatty acids by fatty acid synthase complex (adding C2).
77
What molecules are required for lipogenesis to occur?
ATP and NADPH.
78
How do glucagon/ adrenaline and insulin assert their effects on hormone sensitive lipase?
Glucagon/ adrenaline phosphorylates hormone sensitive lipase, activating it.
Insulin dephosphorylates hormone sensitive lipase, inhibiting it.
79
How do glucagon/ adrenaline and AMP, and insulin and citrate assert their effects on acetyl-CoA carboxylase?
Glucagon/ adrenaline phosphorylate the enzyme, and AMP binds allosterically, inhibiting it.
Insulin dephosphorylates the enzyme, and citrate binds allosterically, activating it.
80
What is the structure of a lipoprotein, and what can they carry?
It is a phospholipid mono layer with a small amount of cholesterol, in a micelle shape.
It has integral and peripheral apolipoproteins associated to it.
It can carry cholesterol esters, fat soluble vitamins and TAGs.
81
How do the lipoproteins differ from each other?
They contain different apolipoproteins, and different TAG, cholesterol and cholesterol ester contents.
82
What are the main apolipoproteins associated with HDL and the other lipoproteins?
HDL = apoAI.
VLDL, ILD and LDL = apoB.
83
What are the two different fates for TAGs released by VLDLs based on their location?
In muscle, the TAG is used for energy.
In the liver, the TAG is stored as fat.
84
What are the different percentages of TAG required for the conversion between VLDL, ILD and LDL?
VLDL depletes to 30% to become ILD.
IDL depletes to 10% to become LDL.
85
How can cells requiring additional cholesterol obtain cholesterol from HDL?
Using scavenger receptors.
86
How can HDL take cholesterol from peripheral tissues, and from VLDL?
The ABCA1 receptor from peripheral tissues.
Through the cholesterol-exchange transfer protein from VLDL.
87
What are hyperlipoproteinaemias caused by and what can there be defects in?
Caused by over-production or under-removal of lipoproteins.
Defects in enzymes, receptors or apolipoproteins.
88
Where do foam cells accumulate and what do they form?
They accumulate in the intima of the blood vessel wall, forming a fatty streak.
89
What do PCSK9 inhibitors do?
They inhibit the breakdown of LDL receptors in liver cells, meaning more LDL is removed from the plasma.
90
Where does haemopoiesis occur in foetus’, in infants and in adults?
In foetus’, it occurs in the yolk sac and then the spleen and liver.
In infants, it occurs throughout the skeletons bone marrow.
In adults, it occurs in the axial skeleton bone marrow.
91
What does haemopoiesis use and what are the 5 categories of lineage pathways?
It uses haemopoietic stem cells.
The 5 categories are:
- Thrombopoiesis.
- Granulopoiesis.
- Monocytopoiesis.
- Erythropoiesis.
- Lymphopoiesis.
92
What do erythropoietin and thrombopoietin regulate? Where are they secreted from?
EPO = stimulate formation of RBCs, secreted by the kidney.
Thrombopoietin = stimulates formation of platelets, secreted by the liver and some by the kidney.
93
What can happen to the haemopoietic stem cells in myeolfibrosis or thalassaemia?
They can migrate to the liver or spleen to undergo extramedullary haemopoiesis.
94
What do the red and white pulp do?
Red pulp = lined by macrophages to remove old and defective red blood cells.
White pulp = lined with white cells to remove encapsulated bacteria, mainly.
95
Where do you start palpating for splenomegaly?
The right iliac fossa.
96
What encapsulated bacteria are you at increased risk of sepsis with hyposplenism? What must be given to patients?
Neisseria meningitidis.
Haemophilus influenzae.
Streptococcus penumoniae.
They must be given lifelong antibiotic prophylaxis and vaccinations.
97
What are the characteristics of red blood cells?
They live for 120 days.
Biconcave shape.
Have no nucleus or mitochondria.
98
State some functions of red blood cells.
Deliver oxygen to tissues.
Carry haemoglobin, and maintain it in its ferrous state.
Maintain osmotic equilibrium.
Generate energy.
99
What are some features haemoglobin?
A tetramer of 2 pairs of alpha and beta chains, each with its own haem group.
Globin gene clusters are on chromosomes 11 and 16.
It binds to oxygen to carry out round by the body and undergoes a conformational change to increase the affinity of it.
There are different types of Hb with different combinations of globin chains.
100
What age do infants switch from foetal to adult haemoglobin?
3-6 months.
101
What are the 4 proteins involved in hereditary spherocytosis?
Spectrin - cross links the actin cytoskeleton to the plasma membrane.
Ankyrin - links integral membrane proteins (band 3) to the spectrin.
Band 3 - facilitates chloride-bicarbonate exchange. It also bind ankyrin and protein 4.2.
Protein 4.2 - ATP-binding protein that is associated with band 3 and ankyrin.
102
What is bilirubin conjugated with in the liver?
Glucuronic acid.
103
What is the maturation of neutrophils controlled by, and what are some other things that it does to neutrophils?
The hormone G-CSF.
It increases production and enhances chemotaxis and phagocytosis ability of neutrophils.
104
What are monocytes, what do they differentiate into and what causes proliferation of them?
They are the largest blood cell that circulates in the blood for 1-3 days, before entering tissues.
Here, they differentiate into macrophages or dendritic cells.
Bacterial infection, inflammatory conditions, myeloproliferative disorders and carcinomas cause proliferation of monocytes.
105
What is the life of an eosinophil and what do their granules contain?
They circulate in the blood for 3-8 hours before living in tissues for 8-12 days.
Their granules contain cytotoxic proteins such as elastase.
106
What are the 3 types of lymphocyte?
B-cells, T-cells and natural killer cells.
107
What is spectrophotometry and flow cytometry, and what are they used to measure?
Spectrophotometry = the amount of light absorbed, used to measure haemoglobin after cells have by lysed by a hypotonic solution.
Flow cytometry = impedance counting and different scatters to measure numbers and sizes of cells.
108
What is the PCV/ Hct?
The proportion of blood that is made up of RBCs.
109
What is the Hb value and what is its units?
It is the concentration of haemoglobin, given in g/L.
110
What is RDW used for?
To see when an iron deficient anaemia began developing.
If the anaemia is haemolytic.
111
How can erythropoiesis be reduced or dysfunctional?
Reduced - reduced EPO production from the kidney, due to anaemia of chronic disease (and less iron), kidney failure, etc.
Dysfunctional - the receptors that EPO binds to cannot stimulate production of RBCs, myelofibrosis so less haemopoietic stem cells, myelodysplastic syndromes.
112
What is an inherited cause of haemolytic anaemia, and how does it manifest?
Hereditary spherocytosis - mutations in genes coding for ankyrin, spectrum, protein 4.2 or band 3.
Leads to less flexible cells that are damaged more easily, and so are removed faster by the RES.
113
How does a G6PDH deficiency cause anaemia?
Less GSH able to be reformed and so the cells are more prone to oxidative damage:
- Lipid peroxidation leads to cell membrane damage.
- Aggregations of haemoglobin; Heinz bodies.
Red cells removed by the RES.
114
Outline some causes of excessive bleeding that may lead to anaemia.
Acute blood loss = childbirth, injury, surgery, ruptured blood vessel.
Chronic NSAID use = can cause GI bleeding as platelets less effective and effects on epithelium.
Chronic bleeding:
- Heavy menstrual periods.
- Kidney, bladder, or GI tumours.
- GI ulcers.
115
What happens in autoimmune haemolytic anaemias and what is the anatomical result on the body?
Autoantibodies bind to the red cells and they are destroyed by macrophages in the spleen.
This leads to splenomegaly.
116
What are some features of reticulocytes?
They are immature red blood cells - take around 2 days to mature.
They have no nucleus but still have some mitochondria.
They are larger than normal red blood cells.
117
Where is folate absorbed, stored, how long can the stores last and where is it converted to tetrahydrofolate?
Absorbed in the duodenum and jejunum.
Stored in the liver with stores lasting up to 3-4 months.
Converted to FH4 in intestinal cells.
118
When should folate be given and for what reason?
It should be given in folic acid form to women before pregnancy, for the first 12 weeks of pregnancy to prevent neural tube defects.
119
What are some folate deficiency-specific symptoms?
Reduced sense of taste.
Diarrhoea.
Paraesthesia in the hands and feet.
Muscle weakness.
Depression.
Anaemia related symptoms.
120
Outline vitamin B12 absorption and storage.
Binds to hepatocorrin in the stomach.
Travels to the intestine where it binds to intrinsic factor.
Intrinsic factor-B12 complex taken up into enterocytes by receptor-mediated endocytosis.
Binds to transcobalamin and transported round the body.
Stored in liver for 3-6 years.
121
What are the two types of autoantibody in pernicious anaemia?
Ones that block the binding of B12 to intrinsic factor.
Ones that prevent the B12-intrinsic factor complex from being taken up by receptor mediated endocytosis.
122
What is subacute combined degeneration of the cord caused by and what are the symptoms?
B12/ folate deficiency - folate = neural tube defect, B12 = demyelination.
Symptoms = changes in mental state, gradual weakness, paraesthesia in hands, feet and trunk which worsens.
123
Why does the regulation of iron absorption and transportation need to be so tightly regulated?
There are no mechanisms for iron excretion.
124
Where does the absorption of iron occur?
Duodenum and upper jejunum.
125
What is the function of hepcidin?
It binds to ferroportin and induced internalisation and degradation, inhibiting the use of iron.
126
How is hereditary haemochromatosis treated?
Regular venesections.
127
What are the different haemoglobin types and their compositions?
A = 2a, 2beta.
A2 = 2a, 2delta.
F = 2a, 2gamma.
128
How many genes for the haemoglobin subunits are found on each chromosome?
For alpha, 4 genes are found on chromosome 16. Delta and gamma are also found on this chromosome.
For beta, 2 genes are found on chromosome 11.
129
What are the 4 types of alpha-thalassaemia, and what are their characteristics?
1 alpha gene deletion is a silent carrier - they are asymptomatic.
2 alpha gene deletions is alpha-thalassaemia trait - they have mild anaemia with microcytic and hypochromic RBCs.
3 alpha gene deletions is Hbh disease - it moderately severe with microcytic, hypochromic RBCs with target cells and Heinz bodies.
4 alpha gene deletions is hydrops fetalis - intrauterine death.
130
What are the 3 types of beta-thalassaemia, the characteristics and genotype, and the treatment?
B-thalassaemia minor/ trait - asymptomatic with some microcytic and hypochromic RBCs. It is heterozygous with one abnormal gene B0/+ (loss of reduction in globin production).
B-thalassaemia intermedia - severe anaemia which is genetically heterogenous or mild homozygous. It is treated with regular blood transfusions.
B-thalassaemia major - homozygous of B0/B0 or B+/B+. It’s onset is after 6 months when the HbF has switched and life is transfusion dependent.
131
What is the inheritance pattern of sickle cell disease?
It is an autosomal recessive mutation of a beta-globin gene, changing a GAG codon for a GTG at position 6 - glutamate for valine.
132
What are the two types of sickle cell disease?
Heterozygous, HbS carrier state sate is asymptomatic.
Homozygous, HbSS causes severe sickling syndrome.
133
Why is sickle cell disease part of the human genome, what advantage can it give?
HbS, the heterozygous state, confers protection against malaria.
134
What causes HbS to form the characteristic sickled shape of red blood cells?
In low oxygen states, polymers of haemoglobin form. They can reverse back but when the sickling cycles continue, the shape becomes irreversible.
135
How does the body try to compensate for haemolytic anaemia, and how well can it do this?
Increase in EPO production stimulates the bone marrow to increase production of red blood cells, up to 6 times as much. Once the rate of destruction exceeds this, anaemia develops.
Also increase 2,3-BPG and cardiac output.
136
What can haemolytic anaemia lead to?
RBC breakdown means bilirubin release leading to jaundice and pigment gallstones forming.
The decrease oxygen carrying capacity will cause ischaemia and infarction of cells, increasing potassium release, leading to cardiac arrest.
137
What are the 3 types of inherited red blood cell membrane structure defects? What are they most commonly caused by?
Hereditary spherocytosis - due to a defect in the ankyrin protein.
Hereditary eliptocytosis - due to a spectrin protein defect.
Hereditary pyropoikilocytosis - due to a spectrin protein defect. Severe form of eliptocytosis with an increase in sensitivity to heat.
138
What are the clinical features of myeloproliferative disorders?
Overproduction of one or several blood elements.
Hypercellular bone marrow.
Extramedullary haemopoiesis.
Can transform into acute leukaemia.
139
What are myeloproliferative disorders most commonly caused by?
Point mutations of the JAK2 gene.
140
What is the JAK2 gene, where is it found and what does it do?
It is a cytoplasmic tyrosine kinase, found on chromosome 9.
It causes increased proliferation and survival of haematopoietic precursors.
141
What is polycythaemia?
An increase in circulating red cell concentration. There is a persistently raised haematocrit.
142
What is a relative and absolute polycythaemia?
Relative = normal red cell mass with a decreased plasma volume (usually dehydration).
Absolute = increased red cell mass.
143
What is secondary polycythaemia and what is it caused by?
Increased EPO production, leading to an increase in red blood cell production.
It is caused by:
- EPO injections.
- EPO secreting tumour.
- Central hypoxia; a decrease in oxygen supply to the tissues from altitude, COPS, CO poisoning, etc.
- Renal hypoxia; renal artery stenosis.
144
What can cause thrombocytosis?
Infection, inflammation, haemorrhage, cancer, and redistribution of platelets.
It can also be due to essential thrombocythaemia - a mutation in the JAK2 gene.
145
What is myelofibrosis, and how does it progress? What is required by the end?
Myelofibrosis is where there is fibrosis in the bone marrow.
It starts with a proliferation phase, where haemopoietic stem cells proliferate, then as it progresses, pancytopenia develops. Tear drop RBCs will be present and extramedullary haemopoiesis towards the end.
Blood product transfusions are required later.
146
Why would the patient have early satiety with myelofibrosis?
Extramedullary haemopoiesis will cause splenomegaly to occur. The massive spleen will then compress against the stomach, decreasing appetite.
147
What are the clinical features of chronic myeloid leukaemia?
Very high WCC.
Splenomegaly.
Hyperviscocity.
Bone pain.
Adults.
Excess neutrophils in the bone marrow.
148
What mutation causes chronic myeloid leukaemia and how is it treated?
Translocation between chromosomes 9 and 22.
Treated with imatinib.
149
What is aplastic anaemia?
Pancytopaenia with a hypocellular bone marrow.
150
How do platelets cause their effects?
Adhesion to endothelial wall and Von Willebrand factor.
Activation - change in shape and release of granules.
Aggregation - clumping together of more platelets to form the plug.
151
What is immune thrombocytopenic purpura? How is it treated?
An autoimmune disease where autoantibodies destroy platelets.
It is treated with immunosuppression and IV immunoglobulins.
152
How can inflammatory cytokines cause anaemia?
Iron dysregulation - decrease in iron availability for synthesis of RBCs.
Decrease in responsiveness to erythropoietin from the bone marrow.
Reduced lifespan of red blood cells.
153
What is hepcidin regulated by?
HFE.
Inflammatory cytokines.
Transferrin receptors.
154
What can effects of uraemia be on blood cells?
Damages red blood cells, decreasing their lifespan.
Inhibits megakaryocytes, leading to low platelet counts.
155
When should iron be given, according to the NICE guidelines?
Ferritin < 200micrograms/ litre.
CHr is low.
Given IM or IV if absorption is impaired.
156
What are some disease modifying agents (DMARDs) used to treat rheumatoid arthritis? What else is given?
Corticosteroids.
Chemotherapy.
Biological agents - monoclonal antibodies against the cytokines.
Analgesia and NSAIDs are also given.
157
How can rheumatoid arthritis cause anaemia?
It is an inflammatory condition so inflammation causes functional iron deficiency and decreases EPO production, decreasing RBC synthesis.
Blood loss due to chronic NSAID use.
Also increases the risk of autoimmune haemolytic anaemia.
158
How can liver disease cause anaemia?
Portal hypertension leading to hypersplenism, increasing the breakdown of RBCs.
Oesophageal and gastric bleeding more likely.
Decrease in clotting factors, and thrombopoietin production, decreasing platelets, increasing risk of bleeding.
Inflammation cause cause a functional iron deficiency and decrease in EPO production, decreasing RBC synthesis.
159
Why are target cells seen in liver disease?
Increased cholesterol: phospholipid ratio.
160
How can sepsis lead to clotting abnormalities?
DIC can incur - pathological activations of coagulation, increasing microthrombi formed, decreasing the amount of platelets available.
Increases the risk of bleeding and thrombosis.
161
What is a leucoerythroblastic film and when is it seen?
Immature red and white blood cells, from them spilling out of the bone marrow during stress.
It is seen in:
- Sepsis/ shock.
- Bone marrow infiltration in cancer.
- Primary myelofibrosis.
- Leukaemia.
162
What are some haematological changes seen in cancer, related to red blood cells, neutrophils and platelets?
163
What is homeostasis?
The mechanisms employed to maintain the internal environment, to keep it in dynamic equilibrium.
164
What is the biological clock?
A small group of neurones in the suprachiasmatic nucleus that regulates body cycles.
165
What are some Zeitgeber cues?
Light.
Temperature.
Exercise.
Eating/ drinking pattern.
Social interaction.
166
Where is melatonin released from?
Pineal gland.
167
What are osmolality and osmolarity?
Osmolality = number of solutes in a kilogram of solution.
Osmolarity = concentration of a litre of solution.
168
What are all steroid hormones synthesised from?
Cholesterol.
169
What are the roles of carrier proteins?
To increase the solubility of hormone in plasma.
Increase the half-life of the hormone.
Act as an accessible store.
170
What types of receptors do water-soluble hormones act on?
Tyrosine kinase receptors.
GPCRs.
171
How do tyrosine kinase receptors work?
Two alpha-beta subunits come together through dimerisation.
Autophosphorylation of tyrosine residues occur.
Adapter proteins and signalling complexes are recruited.
Protein kinases are activated and phosphorylate target proteins to produce a cellular response.
172
How do lipid-soluble hormones cause their response?
They bind to nuclear receptors that are on hormone response elements of a DNA strand.
They regulate transcription of a gene.
This produces mRNA which is translated into a protein for a cellular response.
173
Which nuclei in the hypothalamus control appetite?
Arcuate nucleus.
174
What are the stimulatory and inhibitory neurocrine hormones for hunger?
Stimulatory = NPY and AgRP.
Inhibitory = alpha-MSH and beta-endorphin.
175
What type of hormone is PYY and where is it released from? What does it do?
It is a peptide hormone (same as ghrelin) released from the ileum and colon.
It suppressed appetite.
176
What is the blood supply to the pancreas?
Splenic artery supplies the blood.
Portal vein takes the deoxygenated blood away.
177
What are the two types of secretions of the pancreas, what are their structure and what proportion of each are there?
Exocrine - acinar cells. Makes up 99%.
Endocrine - Islet of Langerhans. 1% of cells.
178
What is secreted from the exocrine glands of the pancreas?
Digestive enzymes (lipase, amylase, proteases - in a proenzyme form) to break down foodstuffs.
Bicarbonate ions (secreted from ductal cells), to buffer the gastric acid for appropriate pH for enzyme function.
179
How many cells are in each islets, how many islets are there and what are the major cell types and their secretions?
Around 6000 cells per islet. There are around 1 million islets in the pancreas.
Beta cells secrete insulin.
Alpha cells secrete glucagon.
Delta cells secrete somatostatin.
180
Why does glucagon not have an effect on skeletal muscle?
There is no GPCR alpha-s for glucagon in skeletal muscle.
181
What is the structure of the stored form of insulin?
It is a hexamer which is highly stable, and is readily available.
182
Outline the process of insulin secretion.
Increase in glucose through GLUT2 transporters.
Glycolysis occurs to increase ATP synthesis.
ATP blocks the K-ATP channel.
This depolarises the cell, stimulating VGCC to influx Ca2+.
The Ca2+ binds to insulin-stored vesicles for exocytosis.
183
What is timeline of insulin secretion like?
It is biphasic, meaning that there is an initial burst upon glucose stimulation, followed by a second phase of a gradual increase in insulin secretion.
184
At what point does insulin secretion cease, and what concentration is the maximal response?
Stops of 2.8mmol/L.
Maximal response at 16mmol/L.
185
How does insulin exert its effects?
Insulin binds to the tyrosine kinase receptors, stimulating them to undergo dimerisation.
The receptor auto-phosphorylates.
Signalling complexes are recruited and activated at the cell membrane.
Metabolic pathways and glucose intake are acted upon.
186
How does glucose cause the release of glucagon?
Less glucose entering through GLUT1 transporters lead to a decrease in glycolysis and ATP synthesis.
The decrease in ATP synthesis causes K-ATP channel to close, depolarising the cell.
This stimulates VGCC to open, resulting in an influx of Ca2+ ions.
The Ca2+ ions trigger the vesicles to release glucagon via exocytosis.
187
How does glucagon exert its effects on cells?
Binds to the GPCR, stimulating the activation of the alpha-s subunit.
This binds to the adenylyl cyclase, stimulating an increase in cAMP.
This activates the PKA enzyme, which can then phosphorylate intracellular proteins, effecting metabolic pathways and gene expression.
188
In type I diabetes, what attacks and destroys the beta-cells of the pancreas?
Autoantibodies, killer lymphocytes and macrophages.
189
What are the two major factors that pre-dispose to insulin resistance?
Obesity and a sedentary lifestyle.
190
What is the diagnosis for metabolic syndrome?
At least 3 of the following 5:
- Abdominal obesity = waist circumference of >102 in men and >88 in women.
- Hypertriacylglycerol = >1.7mmol/L
- Low HDL = <1mmol/L in men and <1.3mmol/L in women.
- Hypertension of >130/85 mmHg.
- Fasting glucose of > 6.1mM.
191
What is last-line treatment for type II diabetes?
Bariatric surgery.
192
How can we monitor diabetes mellitus?
Capillary testing for blood glucose.
Urine or plasma ketone testing.
Flash continuous glucose monitoring.
193
Where, anatomically, is the pituitary gland located?
Sella turica - a bone socket.
194
Where do the anterior and posterior pituitary glands develop from?
Anterior pituitary = oral ectoderm, from primitive gut tissue.
Posterior pituitary = neuroectoderm, from primitive brain tissue.
195
Where are ADH and oxytocin stored in, specifically, and what are they released through to travel to the posterior pituitary?
Stored in the median eminence of the hypothalamus and released into the infundibulum.
196
What are tropic and trophic hormones?
Tropic hormones affect the release of other hormones in the target tissue.
Trophic hormones affect growth.
197
What type of hormone is growth hormone, and what is its primary effect exerted through?
It is a protein hormone that stimulates insulin-like growth factors for growth-promotion.
198
What happens if there is a growth hormone deficiency in childhood, what are the effects on the person?
Pituitary dwarfism - a proportionate dwarfism.
It can be a complete or partial deficiency in growth hormone which decreases the rate of growth and leads to delays or no sexual development during teen years.
199
What does growth hormone excess in children and adults result in?
In childhood, before the epiphyseal growth plates have fused, it results in gigantism.
In adults, after the epiphyseal growth plats have fused, it results in acromegaly.
200
What are the two types of insulin like growth factors (IGFs) and how do their secretion methods produce their effects?
IGF2 is involved in fetal growth, and IGF1 is involved in adult growth.
They act via paracrine, autocrine or endocrine functions to increase cell growth, number and increase the rate of protein synthesis.
201
What modulates IGFs availability?
Binding proteins.
202
What will a person with an upwards growth of a pituitary tumour present with?
Visual field loss due to pressure on the optic chiasm.
Specifically, they will have bitemporal hemi-anopia.
203
What will a person with a lateral growth of a pituitary tumour present with?
Headaches and double vision.
204
What can a gonadotropin deficiency result in in children and adults?
Children - delayed puberty.
Adults - loss of secondary sexual characteristics. Loss of periods is an early sign in women.
205
What is the order of hormone loss in hypopituitarism?
Growth hormone.
Gonadotropin.
TSH and ACTH.
206
How do you test for a hormone deficiency and a hormone excess?
Hormone deficiency = stimulation test.
Hormone excess = suppression test.
207
What are stimulation and suppression tests for the adrenal and growth hormone axis?
Adrenal:
- Stimulation = synacthen (cortisol) and insulin stress test.
- Suppression = dexamethasone test.
Growth hormone:
- Stimulation = insulin stress test.
- Suppression = glucose tolerance test.
208
How do you classify a small and large prolactin tumour?
Small tumour = micro-adenoma < 1cm.
Large tumour = macro-adenoma > 1cm.
209
What will something blocking the pituitary stalk cause, and why?
It will cause excess prolactin release. This is because prolactin is not stimulated by the hypothalamus, but it is inhibited by it - blocking the inhibition means more prolactin will be released.
This is called disinhibition.
210
What are the levels of prolactin indicative of and what is the treatment for each?
If it is very heigh (>5000) then it is likely to be a prolactin-secreting tumour and so it is treated with dopamine agonists.
If it is high but less than 5000, it is likely to be disinhibition and a non-functional adenoma blocking the pituitary stalk which is removed via surgery.
211
What receptor does a dopamine agonist act on, and what are some examples?
D2 receptors, such as bromocriptine and cabergoline.
212
What are some long-term complications with untreated acromegaly?
CV death.
Colonic tumours.
Irreversible bodily changes.
Hypertension and diabetes.
213
What tests are done to confirm acromegaly?
Elevated GH in the blood.
Elevated IGF-1 in the blood.
Failure to suppress GH - oral glucose tolerance test.
214
What is external beam and gamma knife radiotherapy?
External beam - multiple short burst of radiation over several weeks.
Gamma knife - high concentration of radiation one single time.
215
What is Cushing’s disease? What are the symptoms?
An ACTH-secreting tumour, causing:
- Purple striae on the abdomen.
- High blood pressure and diabetes.
- Osteoporosis.
- Abdominal and facial rounding.
- Skinny and weak arms and legs.
216
What is the difference between cranial and nephrogenic diabetes insipidus?
Cranial = vasopressin deficiency.
Nephrogenic = vasopressin resistance in the kidneys.
217
What are some consequences of diabetes insipidus? What can it be treated with?
Severe dehydration with hypernatraemia.
Reduced consciousness, coma and death.
It can be treated with desmopressin.
218
What is the clinical presentation of pituitary apoplexy?
Sudden onset headache.
Double vision.
Cranial nerve palsy.
Hypopituitarism.
219
Where are steroid hormones synthesised?
Adrenal glands and gonads.
220
How do corticosteroids exert their actions?
They diffuse across the plasma membrane of target cells.
They bind to glucocorticoid receptors.
The chaperone proteins dissociate.
The ligand-receptor complex diffuses into the nucleus, through the nuclear pores.
Dimerisation with another receptor and bind to a glucocorticoid response element, or the complex can bind to transcription factors.
Regulates gene transcription.
221
How does aldosterone exert its effects?
It binds to aldosterone receptors, up-regulating the sodium/ potassium pump, promoting re absorption of sodium and water, increasing blood volume and pressure.
222
How does cortisol have a glucose sparing effect?
It inhibits insulin-induced GLUT4 translocation onto muscle cells, preventing the intake of glucose into muscle cells.
223
What disease can cause Addison’s disease?
Tuberculosis.
224
What androgens are released by the zona reticularis, and what are they converted to in men and women?
DHEA (dehydroepiandrosterone) and androstenedione.
In men, DHEA is converted to testosterone.
In women, DHEA is converted to oestrogen (only source after menopause).
225
What biochemical tests would be performed for adrenal medulla hormone excess/ deficiency suspicions?
24 hours urine catecholamines.
24 hours urine metanephrines - the breakdown products.
Plasma metanephrines - more sensitive than 24 hour urine.
226
What radiological assessments can be done to assess adrenal disease?
CT and MRI - assess the size for potential tumours.
PET scan - see if there is a highly metabolic tumour of the adrenal glands.
MIBG - scan to show for adrenaline secretion.
227
What are some causes of primary adrenal failure?
Auto-immune.
Infection - TB, AIDS.
Infiltration - amyloid or haemochromatosis.
Malignancy.
Genetic.
Vascular - haemorrhage or infarction.
Iatrogenic - adrenalectomy, drugs.
228
What are some signs and symptoms of Addison’s disease?
Signs = other auto-immune diseases, general malaise, signs of weight loss, postural hypotension, pigmentation.
Symptoms = fatigue, weakness, anorexia, weight loss, nausea, dizziness, pigmentation, abdominal pain.
229
What is the maintenance for Addison’s disease, after it has initially been treated?
Lifelong glucocorticoid and mineralocorticoid replacement.
Double doses of glucocorticoids when ill and hydrocortisone injections if vomiting.
230
What can the abrupt removal of steroids in chronic users cause?
Addisonian crisis.
231
What androgenic features may be present with Cushing’s syndrome, and why does this occur?
Hirstuism, acne, greasy skin, deep voice. Can also cause alopecia and clitoromegaly if it is due to a highly-secreting tumour.
It does this as cortisols structure is similar to that of androgens and so, when in excess, can bind to the receptors and stimulate similar effects.
232
How is adrenal Cushing’s syndrome treated?
Adrenalectomy - laparoscopic surgery to remove the tumours.
233
What are the two most common causes of primary hyperaldosteronism and what does the blood show?
Aldosterone-secreting adrenal adenoma - Conn’s syndrome, and bilateral adrenal hyperplasia.
There would be an increase in blood pressure with low potassium. There would be a high aldosterone to renin ratio.
234
What are the treatments for primary aldosterone?
Surgery to remove the tumour or spironolcatone.
235
What is the inheritance pattern of congenital adrenal hyperplasia, and what does the presentation depend on?
It is an autosomal recessive disease.
The presentation depends on the enzyme defect.
236
What is the presentation and treatment of congenital adrenal hyperplasia?
Due to the loss of mineralocorticoids and glucocorticoids, there will be:
- Hyponatraemia.
- Hyperkalaemia.
- Hypotension.
- Hypoglycaemia.
- Ambiguous female genitalia.
The initial treatment is of the adrenal crisis - give IV hydrocortisone, glucose and saline. Maintenance will be glucocorticoid and mineralocorticoid treatment. Corrective surgery may be done for the female genitalia.
237
What is a paraganglioma?
A tumour outside the adrenal medulla that causes excess catecholamine secretions.
238
What are acute crises of phaeochromaytomas/ paragangliomas?
Hypertensive crisis, encephalopathy, hyperglycaemia, cardiac arrhythmias and sudden death.
239
What is the management for phaeochromaytomas/ paragangliomas?
Alpha-adrenoceptor antagonist, such as phenoxybenzamine.
Beta-adrenoceptor antagonists, such as bisoprolol.
Surgical excision.
Vasodilation and IV fluids.
240
What are the main causes of phaeochromaytomas/ paragangliomas?
Genetic causes.
Other cancers metastasising can also cause them.
241
What does congenital adrenal hyperplasia lead to?
Low cortisol and aldosterone.
Often high androgens in males.
242
What is the relationship between the thyroid and parathyroid glands?
They are distinct glands, not as one.
The 4 parathyroid glands are usually associated to the back of the thyroid.
243
What does colloid contain deposits of, and what is colloid classed as?
Contains deposits of thyroglobulin that is used for the synthesis of thyroid hormone.
It is extracellular, by inside the follicle.
244
What is the function of thyroglobulin?
It acts as a scaffold for the formation of thyroid hormones to occur on. Proteolysis of the thyroid hormones releases them.
245
What is dietary iodine found in, and how is it taken up in the small intestine, and then into the thyroid epithelial cells?
Iodine is found in dairy, grains, meat, vegetables, eggs and mostly in iodised salts.
It must be reduced to iodide before it can be taken up.
Once in the blood, it is taken up by the thyroid epithelial cells by the sodium-iodide symporter.
246
Outline the process of thyroid hormone synthesis.
Iodide is taken up through the sodium-iodide symporter.
The iodide is then oxidised to form iodine by thyroid peroxidase.
Thyroid peroxidase then iodinates the tyrosines whilst still attached to the thyroglobulin.
Coupling of MITs and DITs occurs to form T3 and T4, facilitated by thyroid peroxidase.
The colloid is then taken back into the follicular cells via pinocytosis and bound with a lysosome for protein degradation, releasing the T3 or T4.
247
What is the negative feedback loop of thyroid hormone?
Low T3 and T4 levels stimulate TRH to be released from the hypothalamus.
TRH stimulates the anterior pituitary to release TSH.
TSH has a negative feedback effect, inhibiting TRH release. TSH also stimulates the thyroid gland to release thyroid hormone.
T3 and T4 then act on cells around the body, but also inhibit the anterior pituitary from secreting TSH and the hypothalamus from secreting TRH.
248
What is the structure of TSH?
It is a glycoprotein hormone made of an alpha and beta subunit.
The alpha subunit is also present in FSH and LH, but the beta subunit provides the specific biological activity.
249
How does TSH produce its effects, predominantly?
the beta subunit binds the the alpha-s-GPCR, activating it.
The g-alpha subunit then releases and binds to adenylyl cyclase, increasing the synthesis of cAMP.
The cAMP then activates the PKA
PKA then stimulates the pinocytosis of colloid, proteolysis of thyroglobulin and release of T3 and T4.
250
How else can TSH exert its effects?
Binds to the G-alpha-q GPCR, activating it.
This releases the alpha-q subunit, which activates phospholipase C.
This stimulates the release of DAG and IP3.
Ca2+ is released into the cell and PKC is activated, stimulating the synthesis and release of T3 and T4.
251
How does thyroid hormone enter the cell to bind to the nuclear receptor?
Thyroid hormone transporters.
252
What are some genes that are activated by thyroid hormone?
Sodium/ potassium ATPase.
PEPCK.
Cytochrome oxidase.
Calcium ATPase.
253
What are some causes of hypothyroidism?
Failure of the thyroid gland.
TSH or TRH deficiency.
Inadequate iodine in the diet.
Autoimmunity (Hashimoto’s disease).
Post-surgery.
Congenital.
Anti-thyroid drugs.
Post-partum thyroiditis.
254
What are some general symptoms of hypothyroidism?
Obesity.
Lethargy.
Intolerance to cold.
Bradycardia.
Dry skin.
Alopecia.
Hoarse voice.
Constipation.
Slow reflexes.
255
What are some symptoms experienced by hypothyroidism in infants?
Cretinism - nervous system does not develop properly:
- Dwarfed stature.
- Mental deficiency.
- Poor bone development.
- Slow pulse.
- Muscle weakness.
- GI disturbances.
256
What are some symptoms experienced by adults with hypothyroidism?
Myxedema:
- Thick, puffy skin.
- Muscle weakness.
- Slow speech.
- Mental disorientation.
- Intolerance to cold.
257
What is Hashimoto’s disease, and who is it present more frequently in?
An autoimmune disease that leads to the destruction of thyroid follicles and hypothyroidism.
It is the most common disease of the thyroid and is seen in women 5 times more frequently.
258
What is the treatment of Hashimoto’s disease?
Oral thyroid hormone - T4 as it has a longer half-life.
Normally 50-200micrograms per day in a single dose.
259
What are some causes of hyperthyroidism?
Grave’s disease.
Toxic multinodular goitre.
Solitary toxic adenoma.
Excessive T3 or T4 therapy.
Drugs, such as amiodarone.
Ectopic thyroid tissue.
Thyroiditis.
260
What is Graves’ disease?
It is an autoimmune condition where thyroid stimulating immunoglobulin is produced that stimulates the TSH receptor of the thyroid gland to produce T3 and T4.
261
What are the symptoms of hyperthyroidism?
Weight loss.
Heat intolerance and sweating.
Tachycardia (palpitations).
Fatigue and weakness.
Hyper-reflexive.
Exophthalmos - bulging eyes.
Goitre.
Loss of libido.
Tremors.
262
What is thyroid scintigraphy?
Technetium-99m is an isotope used to scan the thyroid with a gamma camera. It has a half-life of 1 day.
263
What else can technetium-99m be used for?
DEXA (bone) scan.
Myocardial perfusion imaging.
Brain imaging.
264
What are antithyroid drugs used to treat and what are the method of action?
Used to treat an overactive thyroid by blocking the formation of thyroid hormone.
Carbimazole, which is converted to methimazole to prevent thyroid peroxidase from working.
265
Why does the thyroid gland move on swallowing?
It is invested by the pre-tracheal fascia.
266
What are the serum markers of an under active thyroid?
High TRH and TSH, and low T3 and T4.
267
What are the serum markers of an overactive thyroid?
Low TRH and TSH, and high T3 and T4.
268
What is a lingual thyroid?
Ectopic thyroid, found at the back of the tongue.
269
What is hypothyroidism treated with, and what determines the dose? How long should blood tests take to normalise?
Levothyroxine.
The severity of the disease determines the dose. A high TSH suggests more levothyroxine should be given, and a low TSH suggests less should be given.
Should take 8 weeks for normalisation of blood tests.
270
What is a myxoedema coma? How should it be treated?
Severe hypothyroidism, usually in the elderly.
Hypothermia and fluid overload in the heart causes pericardial effusion.
IV fluid and levothyroxine to be given rapidly.
271
What is lid lag and lid retraction?
Lid retraction is where the eyelid is stimulated to contract by sympathetic innervation, pulling the eyelid back, causing the eye to protrude.
Lid lag is where the eyelids are slower to close.
272
What is thyroiditis and what can cause it?
Inflammation of the thyroid that releases thyroxine into the circulation, causing hyperthyroidism.
It can be caused by viral infections, post-partum, amiodarone can cause it.
273
What are some treatment options for hyperthyroidism?
Carbimazole.
Beta-blockers for symptoms control.
Surgery.
Radioactive iodine.
274
What is a thyroid crisis, and what are some symptoms?
A rare condition where excess thyroid hormone released. It can cause:
- Hyperpyrexia.
- Tachycardia.
- Cardiac failure.
- Liver dysfunction.
275
Why does Grave’s disease need to be monitored during pregnancy?
The autoantibodies can cross the placenta and cause hyperthyroidism of the baby.
276
What is a thyroglossal cyst?
Nodule that is exactly midline of the throat and moves up when they stick their tongue out.
277
What investigations are done with suspected thyroid cancer? What is done if it is?
Thyroid ultrasound.
Fine needle aspiration.
CT of the thorax and mediastinum.
Surgical removal.
278
What is the formation of the parathyroid glands, embryologically?
The upper 2 glands are formed from the internal parathyroid gland and the lower 2 glands are formed from the external parathyroid gland.
279
What type of hormone is parathyroid hormone?
Peptide hormone.
280
What non-cancerous causes are there for hypercalcaemia but low PTH? Why is the PTH low?
Tuberculosis.
Sarcoidosis.
Granulomas.
The PTH is low because they stimulate the production of vitamin D, so negative feedback of calcium levels decrease PTH secretions.
281
What is primary hyperparathyroidism?
A benign parathyroid adenoma, leading to high PTH levels and a high calcium concentration.
282
What are the 2 general causes for hypocalcaemia?
Vitamin D deficiency.
Hypoparathyroidism.
283
What would the biochemistry of a vitamin D deficiency look like?
Low vitamin D, calcium and phosphate.
High PTH.
284
What are some causes of vitamin D deficiency?
Lack of sunlight.
Pigmented or covered skin.
Gastrointestinal disease.
Kidney disease.
285
What is the biochemistry of hypoparathyroidism?
Low calcium, low PTH.
High phosphate.
286
What are some causes of hypoparathyroidism?
Surgical damage or removal of the glands.
Pathology of the parathyroid gland - infection, inflammation, autoimmune, etc.
Failure of the parathyroid glands to develop during embryology.
287
What should be done in acute severe hypocalcaemia?
Airway and conscious levels should be assessed.
ECG and heart needs to be monitored.
Intravenous calcium should be given.
288
What does growth hormone stimulate?
Protein synthesis.
Gluconeogenesis.
Lipolysis.
Glycogenolysis.
289
How do most substances transfer from the mother to the fetus, what about glucose?
Most substances transfer by simple diffusion down the concentration gradient.
Glucose is the principal fuel for the fetus and is transported by GLUT1.
290
What constitutes the fetoplacental unit?
The placenta, fetal adrenal glands and the fetal liver.
291
What are some hypothalamic-like hormones released from the placenta?
Corticotropin releasing hormone.
Gonadotropin releasing hormone.
Thyrotropin releasing hormone.
Growth hormone releasing hormone.
292
What are some pituitary-like hormones released from the placenta?
ACTH.
Human chorionic gonadotropin.
Human chorionic thyrotropin.
Human placental lactogen.
293
What are 2 important placental steroid hormones?
Progesterone.
Oestriol.
294
In the first 20 weeks, what happens to the insulin/ anti-insulin ratio, and what does this result in?
Increase in the ratio, resulting in an anabolic state for increased nutrient storage.
295
What are the main anti-insulin hormones?
Corticotropin releasing hormone.
Human placental lactogen.
Progesterone.
296
What happens to the insulin/ anti-insulin ratio in the second half of pregnancy?
It decreases.
Despite insulin also increasing, anti-insulin levels increase much faster.
297
What are the 3 known causes of gestational diabetes, and what is the main cause?
The main cause is beta-cell dysfunction due to obesity and chronic insulin resistance.
The other 2 causes are:
- Autoantibodies decreasing the function of pancreatic beta-cells.
- Genetic susceptibility.
298
What is crucial to determining whether a woman will develop gestational diabetes?
The starting point of insulin resistance before pregnancy.
299
What does the metabolic response to exercise depend on?
The type of exercise and what muscle groups are used.
The intensity of the exercise.
The physical condition and nutritional state of the individual.
300
How long could ATP ‘stores’ theoretically last?
2 seconds.
301
How long do creatine phosphate stores last for?
5 seconds.
302
How does the length of time that glycogen stores last for differ depending on oxygen supply?
If in anaerobic condition, glycogen lasts for 2 minutes.
If aerobic conditions, glycogen stores last for 60 minutes.
303
How is lactate recycled?
The cori cycle in the liver, synthesising glucose.
