MEH1 Flashcards
(221 cards)
1
Q
What are the 3 main energy consumers of the body?
A
BMR
Activity Muscles (varies most)
Specific dynamic action of food (diet induced thermogenesis)
2
Q
How many kJ in a Kcal?
A
1=4.2
3
Q
What energy is there per gram of fat, carb, protein, alcohol?
A
Fat 37KJ
Carb 17
Protein 16
Alcohol 29
4
Q
What is vitamin B2 used to make?
A
Flavin of FAD
5
Q
What is ATP made of?
A
Adenine
Ribose sugar
Triphosphate alpha beta gamma
Human has 250g of ATP, turn over body weight in ATP per day
6
Q
What is the role of creatine kinase?
A
Transfer a phosphate from ATP hydrolysis to convert creatine to phosphocreatine.
Located in muscle to store energy
Two isoforms muscle and skeletal, can tell if heart attack
7
Q
What is creatinine and why is it useful?
A
Product of spontaneous breakdown of creatine and phosphocreatine.
Excreted by kidney at a constant rate, therefore a measure of muscle mass.
Also a marker of urine dilution. In dilute urine conc lower.
Pregnancy hormones measured against its level
8
Q
What is lactose?
A
Galactose and glucose
9
Q
What is maltose?
A
Glucose and glucose
10
Q
Why don’t we break down cellulose?
A
No Beta 1,4 glycosidic Bond enzyme, only alpha
11
Q
If learned this huge list may prove truly valuable! Name the essential amino acids.
A
Isoleucine, lysine, threonine, histidine, leucine, methionine, phenylalanine, tryptophan, valine
12
Q
What amino acids to children and pregnant women needed?
A
Arginine tyrosine, cysteine for protein synthesis?
13
Q
What vitamins require fat for gut absorption?
A
ADEK
14
Q
What essential fatty acids are needed from diet?
A
Linoleic and linolenic
15
Q
How much water and NA,Cl,K is needed per day for IV fluids?
A
1mmol/kg/day electrolytes
30mmol/kg/day water
16
Q
What can lack of vitamin D lead to ?
A
Rickets - defective mineralisation of bone before epiphyseal closure
17
Q
What can niacin deficiency lead to?
A
Pellagra- reduced NAD levels
Dermatitis, diarrhoea, dementia
18
Q
How much dietary fibre is needed for normal GI function?
A
18g per day
Low can cause constipation and bowel cancer
Increasing fibre intake can reduce cholesterol as it removes bile salts increasing bile production and using cholesterol
Decreases diabetes risk
19
Q
What do we mean by …
estimated average requirement
Lower reference nutrient intake
Reference nutrient intake
A
EAR- Requirement for 50% of people (used for energy)
LRNI- Enough for 2.5% of group
RNI- Enough for 97.5% many need less (used for protein , vitamins, mineral)
20
Q
What should be on an eatwell plate?
A
1/3 veg 1/3 starch 1/9 meat, fish and eggs 2/9 milk and diary 1/18 fat and sugar
21
Q
What is your basal metabolic rate used for?
A
Maintain cells, pumps
Maintain organs, 30% basal muscle tone, 20% each liver and brain, 10% heart
Size , gender, endocrine status and temp affect (12% increase per degree increase)
22
Q
How can physical activity levels increase energy demand?
A
Sedentary 30 KJ/KG/day
Moderate. 65
Very active 100
23
Q
What is a typical body composition?
A
42 kg water 12 fat 11 protein 1 carb 4 mineral
24
Q
How do you calculate and classify BMI?
A
Kg/m^2
<18.5 underweight 18.5-24.9 normal 25-29.9 overweight 30-34.9 obese >35 severely obese
Alternative is waist hip ratio
25
What are the normal ranges for glucose , tg, and lactic acid in blood?
G 3.3-6
TG 0-2
Lactic acid- O.6-2.4
26
What are the causes and features of marasmus?
Negative energy balance, fat stores, glycogen and muscle broken down. Low protein intake and energy intake.
Thin wasted, can see bones. Often in first year of life.
Correct hypoglycaemia, hypothermia and dehydration, replaces electrolytes and micronutrients, cautious feeding.
27
What are the causes and features of kwashiorkor?
Low protein intake, unable to synthesis fat transport proteins. Fatty liver.
Can't make albumin, low oncotic pressure, oedema.
Normal or low energy and fluid intake.
Occurs after breast feeding stops
Actors, swollen legs, moon face, wasting may be masked.
Same treatment as marasmus but extra caution with feeding as liver damage can mean that proteins are converted to ammonia and urea witch is toxic
28
What does the pancreas and produce to break down carbohydrates?
Amylase produces monosaccharides. In saliva too.
29
How are monosaccharides absorbed in the small intestine?
SOdium dependent glucose transports take up at apical surface, glut 2 transport out at basolateral surface
30
Which cells have an absolute glucose requirement?
RBC
Neutrophils
Lens of eye, no blood vessels
Cells of inner kidney medulla
31
What is the committed step of glycolysis?
F6P to F16BP
32
With what enzyme can glycolysis operate anaerobically?
PDH
33
What is lipid peroxidation?
Oxidative degradation of lipids. Free radicals steal the electrons from lipids. Damages cell membranes, causes mechanical stress, leads to haemolysis
34
What are Heinz bodies?
Protein denaturing due to oxidative stress, causes aggregation of haemoglobin, see dark stain in RBC. They bind the cell membrane and alter rigidity. Cause mechanical stress in capillaries. Spleen removes Heinz bodies resulting in blister cells, sign of G6PD deficiency
35
Which molecules contain nitrogen?
AA, proteins, bases, porphyrin, creatine, NT, hormones
36
What do we mean by positive and negative nitrogen balance?
Positive means we get growth, recovery from malnutrition, and good for pregnancy
Negative can be caused by trauma , infection, malnutrition
37
What is the fate of dietary and cellular proteins?
Converted to amino acids in digestion and proteolysis.
Transported to liver
Produce carbon Skeleton for gluconeogenesis (glycine, glutamate) and ketone production for energy ( lysine, leucine)
Produce ammonia and urea, urine
38
What is Cushing syndrome?
Excess cortisol leads to protein degradation, get weak skin and striae formation on belly. Round red face, hypertension
39
Where can we derived the non essential amino acids from?
Glycolysis C3
Ppp C4 C5
Tca C4 C5
Transamination or from ammonia
40
What are the two pathways of nitrogen removal?
Transamination and deamination
41
How do most aminotransferases transaminate?
Use alpha- ketoglutarate to transfer amino group from AA to glutamate. E.g. ALT alanine aminotransferase
42
Why is aspartate aminotransferase an exception?
Uses aspartate to transfer amino group to alpha keto glutarate to form glutamate and oxaloacetate
43
What is the clinical significance of alanine and aspartate aminotransferase (ALT, AST)?
```
ALT converts alanine to glutamate
AST converts aspartate to glutamate
Both need vitamin b6
Key measures of liver function
Indicate hepatitis, autoimmune liver disease, toxic injury, death cap mushroom and acute liver failure
```
44
How does deamination remove nitrogen?
Liberates amino group from AA as ammonia in liver and kidney. Ammonia converted to ammonium, both toxic , removed as urea and excreted.
Keto acids produced can be used for energy
45
How are amino acids and keto acids related?
Keto acid =amino acid- amino group
46
What is the structure and function of urea?
```
NH2CONH2
High N content
Non toxic and water soluble
Inert, bacteria can convert it to ammonia
Osmotic role, excreted in urine
```
47
What are the key features of the urea cycle?
Occurs in liver and involves 5 enzymes. Enzyme levels relate to need to dispose ammonia. High protein diet induces enzymes, and low protein suppresses.
48
What is redeeming syndrome?
Refereeing of malnourished increases protein levels but the enzymes are not functional or enough made. Get ammonia toxicity.
49
What are the risk factors for refereeing syndrome?
BMI less than 16
15% weight loss in 3-6 month
10 days or more little nutrition
Re feed at 5-10 kcal/kg/day
50
What can autosomal recessive defects in urea cycle enzymes lead to?
Hyperammonaemia and intermediate accumulation
51
What are the symptoms and management of urea cycle defect?
Severity depends on nature and amount of protein
If severe see soon after birth, mild may be delayed
Get vomiting, lethargy, irritability, mental retardation, seizure and coma
Need low protein diet and to replace amino acid with keto acid
52
Why is ammonia toxicity bad?
Interference with amino acid transport and protein synthesis • Disruption of cerebral blood flow • pH effects (alkaline) • Interference with metabolism of excitatory amino acid
neurotransmitters (e.g. glutamate and aspartate) • Alteration of the blood–brain barrier • Interference with TCA cycle (reacts with a-ketoglutarate to
form glutamate)
Blood levels 25-40microM
53
What are the two mechanisms of ammonia removal?
Combined with glutamate to form glutamine, transported to kidney where cleaved to form substrates for excretion and liver for urea cycle
Combined with pyruvate to form alanine. Transported to liver for transamination. Amino group fed to urea cycle, pyruvate back to tissues
54
What do we test for in aa baby heel prick test?
In born errors of metabolism
CF
Sickle
Congenital hyperthyroidism
55
What is phenylketonuria and how do we treat it?
Phenylalanine hydroxylase deficiency, get accumulation of dietary and endogenous phenylalanine.
Two affects: build up of phenylketones (musty urine) and no production of tyrosine.
Can't make adrenergics, dopamine, melanin, thyroid hormone, certain proteins.
Get Severe intellectual disability • Developmental delay • Microcephaly (small head) • Seizures • Hypopigmentation
Avoid high protein and artificial sweeteners
56
What causes homocystinurias and how is it managed?
Can't break down methionine, get excess homocystine the oxidised form of homocysteine. Don't produce cysteine
Defect in cystathionine b -synthase mostcommon
• Affects connective, tissue, muscles, CNS, CVS,
• Low-methionine diet • Avoid milk, meat, fish, cheese,
eggs • Nuts, and peanut butter also contain methionine • Cysteine, Vit B12 Folate supplement, Betaine, B6
57
How is alcohol metabolised ?
Converted to acetaldehyde then acetate then acetyl coa which enters TCA or fatty acid synthesis.
Produces two NADH
Alcohol and Acetaldehyde DH enzymes
Smaller amounts by p450 or catalase in brain
58
How can alcohol toxicity cause liver damage?
Acetaldehyde accumulation direct toxicity
Excess NADH and acetyl coa alter liver metabolism
Lead to fatty liver , alcoholic hepatitis and alcoholic cirrhosis
59
List some metabolic consequences of chronic alcohol consumption?
Decreases NAD- lactate acidosis, gout as kidney can't excrete Uric acid. Reduced glycerol metabolism, reduced gluconeogenesis and hypoglycaemia. Inadequate fatty acid oxidation
Increased acetyl Coa- increased FA and ketone synthesis, increase TG, fatty liver
60
How does disulfiram treat alcoholism?
Blocks acetaldehyde DH, leads to accumulation of acetaldehyde and toxic build up, get hangover
61
Explain how different free radicals are formed , starting with molecular oxygen.
Oxygen + electron = superoxide + NO radical = peroxynitrate (not a radical but causes oxidative damage)
Superoxide + 2H+ and e = hydrogen peroxide (not radical but reacts with FE2+ to produce) + e and H+ = water and hydroxyl radical. Most damaging, needs converting to water.
62
How can ROS damage DNA?
React with bases leading to mispairing and mutation
React with sugars, breaking strands leading to mutation repair
8oxodg a good marker of ROS damage
63
How can ROS affect proteins?
Denature, change structure, loss function
| May take electrons from cysteines, leads to inappropriate disulfide bond formation between thiol groups
64
Name 3 sources of ROS and their effect
Oxphos - electrons can escape and produce superoxide
Nitric oxide synthase- arginine to citrulline and NO. Leads to vasodilation, neurotransmission and s nitrosylation and toxicity
Respiratory burst- phagocytes release superoxide and hydrogen peroxide. Also produce peroxynitrite which destroy bacteria
65
What are the three types of nitric oxide synthase?
Inos - inducible, high in phagocytes
Enos - endothelial signalling
Nnos - neuronal signalling
66
How do cells defend against superoxide radicals?
Superoxide dismutase converts to hydrogen peroxide
Catalase converts hydrogen peroxide to water and oxygen.
Important in immune cells
67
What are the oxidised and reduced form of glutathione?
Oxidised GSSG disulphide bond between two chains
Reduced 2GSH glycine, cysteine, glutamate
Glutathione reductase and peroxidase
Peroxidase transfers electrons to H2O2 to form h2O. Enzyme requires selenium
68
Name two free radical scavengers
Vitamin E - oxidised to reduce lipid peroxidation, lipid soluble, donates hydrogen iron and electron
Vitamin C- water soluble regenerates reduced vitamin E
69
What is the role of ketone bodies?
To solubilise energy from fat when glucose is low
70
Name 3 ketone bodies
Acetoacetate
Acetone
Beta hydroxybutyrate
71
What is the normal ketone plasma concentration, the starvation conc and diabetes conc?
Normal less 1mM
Starved 2-10
Untreated type 1 greater than 10
72
How does regulation of the enzymes lyase and HMG reductase affect the ketone and cholesterol pathways?
Increased insulin glucagon ratio- indicates high glucose, inhibit lyase produce cholesterol
Decreased insulin glucagon ratio- indicates low glucose, inhibit HMG reductase, ketone body synthesis
73
What diverts acetyl coa from TCA cycle to HMG and fatty acid synthesis?
Increased NADH inhibits isocitrate DH and alpha ketoglutarate DH
74
Which enzymes are used in gluconeogenesis for the irreversible reactions?
PEP carboxylase, oxaloacetate to PEP
G6P phosphatase, g6p to glucose
F16bisphosphatase, 1,6 to 6
75
How is glycogen stored?
As granules in hepatocytes and between muscle fibres. Originates from dimers of glycogenin, builds 1,4 and 1,6 bonds
76
What is a good marker of high glucose?
Glycated haemoglobin
77
What is the normal glucose range and what happens in hypoglycaemia?
4-6mmol/L
2. 8 confusion
1. 7 weak and nausea
1. 1 muscle cramp
0. 6 brain damage and dead
78
After how many hours of glycogenolysis do we get gluconeogenesis starting?
8 hours liver glycogen stores depleted
79
What are the three main precursors for gluconeogenesis?
Lactate via cori cycle, muscle blood liver
Alanine
Glycerol release from adipose tissue (glycerol phosphate to DHAP)
None from acetyl coa as pyruvate dehydrogenase is irreversible
80
What is the course of glucose utilisation?
Glucose from diet , two hours
Glycogenoylsis 1-10 hours
Gluconeogenesis 8+
81
What type of fuel is increased in a obese man compared to normal weight person?
Liver and muscle glycogen and protein remain the same
| Triglyceride levels much higher
82
Where is cholesterol mostly synthesised ?
In the liver, some from diet
83
What are cholesterol esters and how are they formed?
Cholesterol and fatty acid
| Formed by esterification with enzymes LCAT and cholesterol acyl transferase
84
In which apolipoproteins is apoB important?
VLDL
IDL
LDL
85
In which apolipoprotein is ApoAI important?
HDL
86
What are the two types of apolipoproteins and their roles?
Integral, peripheral
Structural, packaging lipids
Functional, ligands for cell receptors and coenzymes
87
What is the RES?
Network of blood and tissue containing phagocytosed cells. Mono, macrophages in lymph and spleen, kupfter cells, histiocytes, microglia
88
What are ferrous and ferric iron?
Ferrous is Fe2+
Ferric is Fe3+
Haemoglobin mainly in ferrous state
89
How is haemoglobin broken down?
Res breakdown into heme and globin. RES breakdown biliverdin and bilirubin.
Bilirubin conjugated in the liver.
Transported in bile duct to intestine
Urobilinogen formed, converted to stercobilin and excretedin faeces.
Or transported in blood to kidneys, excreted in urine.
90
What is erythropoiesis and how does the kidney control it?
Reduce pO2 detected in peritubular kidney cells, increases EPO made, maturation in bone marrow, haemoglobin rise decrease EPO
91
What RBC abnormalities can cause anaemia?
Glycolysis and PPP as they are the producers of ATP and NADPH
92
What are the two main stores of iron?
Ferritin in hepatocytes and haemosiderin in kupfter cells
| Most iron recycled from breakdown
93
Why is haem iron better than non haem iron?
Haem iron Enters enterocytes in ferrous state, so doesn't need converting. Non haem enters in ferric state, needs reducing to ferrous
94
Where does iron whether the body and how is it transported to cells?
Enters apical surface of duodenum and jejunum.
Once in enterocytes converted to ferric form and stored as ferritin or transported through ferroportin on the basolateral side.
Binds to transferrin in the blood which binds transferrin receptors on mostly RBC, hepatocytes and , macrophages.
95
What receptors do fetal enterocytes have?
Lactoferrin receptors for mothers milk
96
What influences the absorption of non haem iron?
Acids increase oxidation to ferrous state
| Alkaline prevent oxidation
97
How does hepcidin prevent iron absorption?
Excreted by liver and kidney when iron high. Decreased by high EPO acitivity. Binds ferroportin on enterocytes , prevents entry into blood. Binds ferroportin on macrophages prevents iron recycling
98
What are the two most common causes of iron deficiency?
Insufficient uptake
| Pregnancy or bleeding, menorrhagia
99
What are the symptoms of iron deficiency?
Tachycardia, tired, reduce exercise tolerance, increase RR. Cardiac symptoms , angina, spooning pale appearance.
100
What are the blood parameters of iron deficiency.
```
Microcytic
Hypochromic (low haemoglobin)
Low serum ferritin
Low reticulocyte haemoglobin content
Anisopoikilocytosis, change in shape and size
```
101
What are two ways we can test for iron deficiency?
Ferritin , if low likely deficient but normal or raised can be deficient as it's an acute phase protein.
CHR- reticulocyte haemoglobin content. Low in patients with thalassemia
102
How can we treat iron deficiency?
Diet, supplements, IM or IV injection, transfusion if severe.
103
What are the dangers of excess iron?
Hydroxyl and lipid radicals, damage DNA protein. Deposits in tissue, get haemosiderin staining.
104
What is hereditary haemochromatosis?
HFE gene product regulates interaction (competes) of transferrin with its receptor. Autosomal recessive Gene Mutated in this disease too much iron enters cells.
Venesection to treat.
Leads to organ damage due to deposition, liver cirrhosis, diabetes, cardiac related, pigmentation
105
What are the affects and treatment of transfusing associated iron overload?
People with thalassemia or myelodysplasia are transfusion dependent.
Should be 200mg iron in 400ml blood
Use chelating agents if too much to delay effects
106
What can cause reduced erythropoiesis and lead to anaemia?
```
Chronic kidney disease reduced EPO
Myelofibrosis
Marrow infiltration- leukaemia
Chemo or toxic insult (parvovirus)
Aplastic anaemia
```
107
What can cause dyserythropoiesis and anaemia?
Anaemia of chronic disease (TB, RA, IBD,)
Reduced RBC lifespan
Marrow lacks EPO response
Iron not released from macrophages
108
What is myelodysplastic syndrome?
Abnormal clones of marrow cells. Immature cells don't mature
Macrocytic anaemia
In elderly
Premature RBC destruction by RES
Also get pancytopenia
Acute leukaemia
Transfusion needed , some may need stem cells or chemo
109
What type of anaemia do B12 and folate cause?
Macrocytic
Building blocks for DNA, necessary for nuclear division, cell cytoplasm lags behind division.
Large RBC , large nuclei, open chromatin
110
How is B12 absorbed?
From diet and microorganisms. Complexes with intrinsic factor in ileum. In blood binds transcobalamin which delivers it to bone marrow and tissue.
111
What B12 absorption deficiencies are there?
Intrinsic factor autoimmune destruction, pernicious anaemia
IF- B12 , crohns
Transcobalamin congenital defect
112
How is folate absorbed?
In yeast, liver, leafy greens.
Absorbed in duodenum and jejunum
Converted to methyltetrahydrofolate, circulates in plasma
113
What are the causes of folate deficiency?
Dietary deficiency and crohns.
Alcoholism, liver disease, heart failure, pregnancy
Increase EPO in haemolytic anaemia, skin diseases
Methotrexate to treat crohns (inhibits dihydrofolate reductase)
114
How is B12 deficiency associated with neurological disease?
Focal demyelination, affects nerves , can cause dementia and depression.
115
What type of anaemia does sickle cell cause, what are the clinical problems in crisis and treatments?
Haemolytic anaemia due to repeated deoxygenation, sickling and shear forces
Anaemia normally mild as Hbs normally gives up O2 well.
Crisis caused by vaso occlusion stroke and retinopathy, iron overload in liver and heart, atrophic spleen due to infarction, RBC can also trap in spleen and get splenomegaly, parvovirus worsens anaemia destroys precursors
Treat BM and blood transfusion, folic acid, prophylaxis, hydroxyurea, reactivate fetal haemoglobin
116
What type of anaemia do you get in thalassemia?
Microcytic, hypochromic.
Excess of other chains form insoluble aggregates which are destroyed in spleen and bone marrow.
Get extramedullary haemopoiesis, splenomegaly and hepatomegaly.
Death caused by EPO mediated iron overload and transfusion iron overload
Treat with transfusion, folic acid, iron chelators, immunisation
117
What are the genotypes and phenotypes of alpha and beta thalassemia?
Beta 2 genes- major(transfusion dependent), minor (asymptomatic), intermedia (major or minor)
Alpha4 genes- silent, trait, haemoglobin H disease, hydrophobic fetalis (intrauterine death)
118
What are Heinz bodies?
Denatured Haemoglobin inclusions in RBC , seen in HbH thalassemia
119
Name some defects of the red cell membrane that lead to anaemia.
Hereditary spherocytosis- haemolytic anaemia
Elliptocytosis
Pyropoikilocytosis
Stomatocytosis
Mechanical damage of valvular disease, vasculitis, DIC,
Burns
120
What red cell metabolism disorders can lead to anaemia?
G6PD deficiency
| Pyruvate kinase deficiency
121
What is autoimmune haemolytic anaemia?
It autoantibodies from B cells bind RBC proteins, target for degradation. Warm and cold types.
See raised bilirubin and lactate dehydrogenase and a raised reticulocyte count
122
What changes do we see in myelofibrosis?
Decreased erythropoiesis, increased RES, extra-medullary haemopoiesis , tear drop RBC as they try to squeeze out.
123
Name three myeloproliferative disorders.
Myelofibrosis
Essential thrombocythaemia
Polycythaemia Vera
124
List some clinical features of myeloprolifertive disorders
```
Extramedullary haemopoiesis
Dominance of clone
Hypercelullar marrow
Fibrotic
Thrombotic and haemorrhagic
Acute leukaemia
```
125
What is a common aetiology of myeloproliferative disorders?
Jax2 gene mutation , a tyrosine kinase, leads to increase survival of haemopoietic precursors
126
What is polycythaemia Vera and how would you diagnose it?
Group of disorders which increase circulating RBC and is classsifed by a persistent high hematocrit. Should be 40% of blood, see >52 men >48 women.
Also jak2 mutation
Some have high platelets and neutrophils.
Mean age 60
127
Why must we not assume polycythaemia Vera is the cause of erythrocytosis?
Erythrocytosis can be relative, decrease in plasma volume due to dehydration
Primary erythrocytosis is polycythaemia Vera
Secondary can be physiological caused by EPO response to hypoxia or inappropriate due to high affinity haemoglobin not releasing o2 causing hypoxia
128
List 3 types of causes of increased EPO in blood
Central hypoxia (CLD, RL shunt, altitude training, CO poisoning), renal hypoxia, cancers
129
What are the clinical features and management of polycythaemia Vera?
Features- arterial thrombosis haemmorhage, Splenomegaly, gout, myelofibrosis, acute leukaemia splenic pain, pruritis
Management
Venesection, aspirin, cvs management, control cell production if gets worse and weight loss
130
What are the two pulps of the spleen?
Red pulp- sinuses line by endothelial macrophages and cords
| White pulp- similar to lymphoid follicles
131
Why does enlarged spleen cause weight loss?
Pushes on stomach and dampens appetite
132
What are the main functions of the spleen?
Sequester and phagocytose RBC
Pool blood, mobilised when needed
Extramedullary haemopoiesis
25%T cells and 15% of B cells here
133
How would you palpate for splenomegaly?
Feel for splenic notch , spleen hits hand as breath, measure from mid clavicular coastal margin to where it hits the hand. Shouldn't normally be able to palpate
134
Name 4 reasons for spleen growth?
Extramedullary haemopoiesis
Portal hypertension and liver disease
Leukaemia
Foreign material , sarcoidosis
135
What is hypersplenism?
Pooling of blood in spleen. Causes pancytopenia and thrombocytopenia.
Risk of rupture as no rib protection. Risk of infarction, sickle cell
136
What the causes of hyposplenism?
Loss of functional splenic tissue
Splenectomy, sickle cell, coeliac
Risk of sepsis from encapsulated bacteria
137
What are Howell jolly bodies?
Caused when spleen doesn't remove red blood cells which fail to expel their nucleus and DNA remains. Signify spleen damage.
138
What is a cytopenia?
Decrease in blood cells
139
What is a cystosis or Philia?
Increase in blood cells
| Neutrophilia, the rest cytosis
140
What cells lead to the formation of a neutrophil?
Myeloblast, promyelocyte, myelocyte, metamyelocyte, band cell, neutrophil
Recombinant G-CSF used to stimulate this in neutropenia
141
When might we see a neutrophilia?
Infection, autoimmune disease, cancer, smoking, haemorrhage, steroids, myeloproliferative disorder
142
Name some removal or use causes of neutropenia.
```
Removal or use:
Immune destruction
Sepsis
Splenic pooling
Cyclic (14-21 days)
Benign ethnic (Afro Caribbean)
```
143
What causes reduced neutrophil production?
```
B12 folate deficiency
Malignancy
Aplastic anaemia
Radiation or chemo
Viral
Congenital
```
144
What are the consequences of neutropenia?
Severe infection, mucosal ulceration, sepsis
145
What is the role of monocytes and what causes monocytosis?
Respond to inflammation, migrate to tissue where become macrophages.
Chronic inflammatory conditions elevate levels. RA, crohns, TB, cancers
146
What is the role of eosinophils?
Involved in the response to parasites and allergens.
Phagocytose via antibody antigen complex, contain granules which destroy.
Mediate drug hypersensitivity and skin inflammation
Serious effects in leukaemia, Hodgkin lymphoma, myeloproliferative conditions
147
What is the role of basophils?
Least common , allergen and inflammation
Heparin histamine hyaluronic acid in granules
Involved in immediate hypersensitivity and myeloproliferative disorders
148
When can you get lymphocytosis?
```
Post splenectomy
Smoking
Infection
Stress
Lymphoproliferative malignancies
```
149
What is aplastic anaemia?
Pancytopenia with hypocellular marrow, no abnormal infiltrate or fibrosis.
150
What can cause pancytopenia?
```
Haematological malignancy (blood cells)
Non haematological malignancy (non blood cells)
```
151
What are the main symptoms of pancytopenia?
Infection, ulcer, fever due to neutropenia
Bleeding and bruising due to thrombocytopenia
Fatigue, dizziness, breathless, chest pain due to anaemia
152
Name 3 sources of HStem cell?
Aspiration of bone marrow (rare)
Mobilised from peripheral blood and collected by leucopheresis
Umbilical cord banks
Need good HLA match, healthy weight and be 15-30
153
In which neurones is our biological clock, and what cues trigger it?
Suprachiasmatic nucleus
Light , temp, social, exercise, eating and drinking
Pineal gland makes melatonin at night
154
What is the difference between osmolarity and osmolality, and what are osmoles?
Osmolarity is osmoles per litre
Osmolality is osmoles per kg
Osmoles are the osmotically active particles. So in one mole of NaCl we have two osmoles, one Na , one CL
Serum should have 275-295 mOsmoles per kg
155
If our blood is hypertonic how does the body respond?
Osmoreceptors in the brain causes the posterior pituitary to release ADH causes reabsorption in kidney and thirst
156
If our blood is hypotonic how does the body respond?
Osmoreceptors in the brain, less ADH release from PP, decrease reabsorption, dilute urine
157
What is the bodies response to hyper and hypoglycaemia?
Hyper- beta cells release insulin, causes Glut4 glucose uptake, glycogenesis
Hypo- alpha cells release glucagon, stimulates glycogenolysis
158
What are the 4 classifications of hormones?
Steroid
Peptide (insulin/glucagon)
Amino acid derivative (AD/NORAD/Thyroid)
Glycoproteins (LH,FSH,TSH)
159
How can hormones be transported in the blood?
Water soluble such as adrenaline and peptides
| Protein bound such as thyroid hormones to thyroxine binding globulin
160
What are the two types of lipid soluble hormone receptors?
Type 1- cytoplasmic receptor, complex enters nucleus
| Type2- hormone binds receptor pre bound to DNA Hormone response element in promoter region. Can relieve repression
161
Which area of the brain is involved in appetite control ?
Satiety centre in hypothalamus. Several clusters of nuclei. Arcuate NUcleus big role in primary stimulation and inhibition
162
Where is the thyroid gland anatomically located?
Front of larynx and trachea , isthmus is at trachea ring 2-3
163
How does the thyroid gland embryologically develop?
First endocrine gland to develop.
3-4 weeks gestation
First appears at floor of pharynx at base of tongue as epithelial proliferation
First descends through thyroglossal duct (mains connected) and migratesdownwards passing in front of hyoid bone. Duct then degenerates.
Continues to final position over next two weeks.
164
Name two defects in thyroid embryology?
Thyroglossal duct cyst- normally dissapears, remnants form cyst near hyoid body, forms swelling. Tongue protrusion moves up.
Lingual thyroid, part of gland remains on tongue
165
Describe the histology of the thyroid gland?
Follicular cells arranged in spheres forms and thyroid follicle with colloid in the centre.
Cells produce thyroid hormones
Parafollicular cells produce calcitonin
Colloid stores thyroglobulins
Parathyroid chief cells produce parathyroid hormone
166
What are the three steps in thyroid hormone production?
Tyrosine residues bind to thyroglobulin. MIT or DIT (iodised tyrosine residues) formed by iodination.
Coupling occurs
DIT and MIT =T3
DIT and DIT = T4
Linked at 3/4 position of aromatic ring
Thyroid peroxidase regulates all 3 steps including the oxidation of iodide to iodine
167
Explain the mechanism of iodine absorption and utilisation
Iodine from diet reduced to iodide before absorption in small intestine.
Iodide taken up through sodium iodide transporters into thyroid epithelial cells
Transported out to colloid where the 3 steps occur
Re Enter thyroid follicle, hormones released into blood
Phagolysosome mediates their release
168
Where and why is T4 converted to T3?
90% is T4 but T3 4x more active
Converted in liver and kidney
80% derived from T4
Transported in blood by thyroxine binding globulin
169
What effects does TSH have?
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Activates Galpha s and q
Causes iodide uptake and oxidation
Thyroglobulin synthesis and iodisation
Colloid pinocytosis
Proteolysis of thyroglobulin
Cell growth and metabolism
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170
Describe some general actions of thyroid hormones
Increase BMR and heat (mitochondria and enzyme synthesis)
Stimulate metabolic pathways (lipolysis, beta oxidation, carb metabolism
Sympathomimetic effects(increase receptor number)
171
Describe some specific effects of thyroid hormone activation
Increase CO and decrease TPR, carry more heat
| Neuronal development and myelination
172
How does thyroid hormone elicit its affects on the cell?
Lipid soluble so enters through transporter and activates nuclear transcription factors. May relieve repression of a gene. Activates Ca/Na atpase and causes increased respiration.
173
Explain how iodine deficiency can affect pregnancy and lead to Cretinism?
Iodine deficiency while pregnant can lead to cretinism
Congenital hypothyroidism
Dwarf stature
Mental deficiency , deaf, gait change, goitre
Weak muscle , slow pulse
Gi upset and blind
174
What is myexedema?
Dermatological changes in hypothyroidism. Non pitting oedema.Word used to mean hypothyroid
Mucopolysaccharide deposit in eyes hand and feet.
Thick puffy skin
Muscle weak
Slow speech
Cold intolerance
Loss of end of eyebrow
175
What is the role of the pre tracheal fascia?
Attaches thyroid gland to trachea and larynx
| Moves up against epiglottis when swallow as larynx moves down
176
What can we use to visualise the thyroid gland?
Oral iodine123,131 takes a day to be incorporated
Iv technetium99, quick , low radiation
Thyroid ultrasound
177
Why is a primary abnormality of the thyroid gland itself the most common abnormality?
Pituitary failure very rare, pituitary adenoma rare to alter TSH levels.
TSH is therefore a good screening tool for hypo and hyperthyroidism
178
What are the main causes of hypothyroidism?
Iodine deficiency
Hashimotos Autoimmune destruction of thyroid follicles
Post surgery removal of thyroid
Congenital
179
What is hoshimotos disease?
Autoimmune disease causing destruction of thyroid follicles. Autoantibodies to thyroglobulin and thyroid peroxidase. Given oral T4, longer half life than T3.
More common in women
180
What are the symptoms of hypothyroidism?
Cold intolerance, weight increase, tired, memory issues, dry skin, puffy, hair loss, carpel tunnel, mennorhagia, muscle weakness , constipation
181
What are the signs of hypothyroidism?
Peaches and cream, bradycardia, hyponeflexia, myxoedma, ascites, pleural effusion
182
What are the causes of hyperthyroidism?
Graves' disease autoimmune
Toxic multinodular goitre
Toxic adenoma
183
What are the symptoms of hyperthyroidism?
Ammenorhagia, weight loss, heat intolerance, sweating, palpitation, diarrhoea, anxious, muscle weakness
184
What are the signs of hyperthyroidism?
Tachy, tremor, bounding pulse, proximal myopathy, lidlag, staring eyes
185
What is Graves' disease?
Thyroid stimulating immunoglobulin stimulate the TSH receptor. Get thyrotoxicosis.
Unique symptoms are exopthalamas, bulging eyes, and pre tibial myxodema
186
What is a toxic multinodular goitre?
In small % of those with a multinodular goitre leads to thyrotoxicosis.
Multinodular goitres common in the U.K. , can enlarge inferiorly and compress trachea behind mediastinum
187
What is a toxic adenoma?
Adenoma of thyroid gland, produces thyroxine. Rest of gland gets suppressed and shrinks due to low TSH levels.
188
How do we treat thyrotoxicosis?
Surgical excision , thyroidectomy
Ablative dose of radioactive iodine
Carbimazole- inhibits thyroid peroxidase
189
Discuss thyroid cancer
Less than 1% nodules malignant. Makes up less than 1% of cancers. Cause no metabolic disturbance. 97% cure rate. Can produce a goitre.
190
What are the 3 classifications of goitre and when are goitres common?
Diffuse
Multinodular
Single nodule
Common in females 7%, hormones affect this. Common at menarch, pregnancy and menapause
191
In what conditions do you get a goitre?
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Graves
Iodine deficient hypothyroidism
Multinodular goitre
Congenital hypothyroidism
Hashimotos
Thyroid cancer
Thyroiditis
```
192
What is the infundibulum?
The pituitary stalk
193
What two hormones come from the posterior pituitary?
Oxytocin- milk let down and uterus contraction
ADH- body water volume
Both produced in supraoptic and paraventricular nuclei of hypothalamus
194
What hormones act on the anterior pituitary?
Produced in hypothalamus, travel down median eminence into hypophyseal portal system. Stimulate inhibit endocrine cells.
```
TRH
PIH
CRH
GnRH
GHRG
GHIH
```
195
What's the difference between a tropic and trophic hormone?
Tropic affects another hormone
| Trophic affects growth
196
What hormones does the anterior pituitary secrete?
TSH
ACTH
LH- ovulation and sex hormones
FSH- egg sperm development
Prolactin- Mammary gland development and milk secretion
Growth hormone - growth and energy, insulin like growth factor.
197
What triggers the HPA axis?
Stress, pain, hypoglycaemia, low bp
198
Explain the control of growth hormone?
Growth hormone releasing hormone
Growth hormone inhibiting hormone(somatostatin)
Released in hypothalamus
Ap produce Growth hormone, cleaved before folding
Act on the liver and muscle to produce IGFs
199
When do growth hormones and IGFs stimulate growth?
GH, long bone growth, length and widen prior to closure of epiphyseal plate
IGFs stimulate bone and cartilage growth after epiphyseal closure
Both maintain muscle mass, promote repair, modulate metabolism
200
What factors increase growth hormone levels?
```
Deep sleep
Stress
Exercise
Decrease glucose and FA
Fasting
```
201
What factors decrease growth hormone?
Rapid eye movement sleep
Increase glucose and FA
Obesity
202
What can growth hormone deficiency cause?
Pituitary dwarfism- proportional, height below 3rd percentile on growth chart. Slower growth or delayed sexual development.
GH therapy good
203
What diseases can excess growth hormone cause?
Acromegaly- large extremities, hand,feet,jaw, confirm with oral glucose tolerance test, see if depresses GH. Normally due to pituitary adenoma.
Excess growth hormone in childhood, gigantism. Rare
204
How are IGFs produced from growth factor?
GH Activates a JAK tyrosine kinase
205
Which IGFs are used in adult and fetal growth?
Adult IGF1
Fetal IGF2
Act on IGF receptors causing hypertrophy and hyperplasia and lipolysis
206
What are the 4 types of IGF receptors and are they mainly metabolic or mitogenic?
Insulin receptor- metabolic
Hybrid receptor- mitogenic
IGF1- mitogenic
IGF2- no TK activity targets for lysosomal degredation
207
Name some mediators of growth other than growth hormone and IGFs?
```
Thyroid hormone
Estrogen
Androgen
Glucocorticoids
Insulin
```
208
How may someone with a pituitary tumour present?
```
Headache, pain, double vision
Eye movement (cranial nerve palsy)
Visual loss, pressure on optic chiasm causes bitemporal hemianopia
```
209
What can hypopituitarism, caused by a tumour lead to?
Decrease in growth hormone leads to reduced stature and QOL
Decrease in LH and FSH causes loss of periods and men with female features. Delayed puberty in kids.
Decreased TSH, hypothyroidism and associated symptoms
Decreased ACTH, low cortisol tired and dizzy, low bp , life threatening
Increase prolactin as loss of inhibitor of prolactin
210
What can hyperpituitarism caused by a micro adenoma lead to?
Commonly affects prolactin, GH, and ACTH
| Rare to affect FSH/LH/TSH
211
What basal blood tests do we take to asses pituitary function?
Thyroid T4,TSH
Gonadal LH, FSH
Serum Prolactin
212
What dynamic blood tests can be done to assess pituitary function?
0900 cortisol test for HPA axis
| Measure GH and IGF1 throughout day or glucose test to see if GH goes down
213
How could you test for Addison's disease (adrenal deficiency)?
Insulin stress test. Cause hypoglycaemia, see if get an adequate cortisol response
214
How could you test for excess HPA activity?
Suppress ACTH with dexamethasone steroid, see if suppresses
215
What are prolactinomas, what symptoms do they cause and how are they treated?
Pituitary tumour secreting prolactin. Can be micro or macroadenomas
Treat with dopamine agonist as dopamine is inhibitory, shrinks tumour , no operation. Antagonist can cause the tumour.
Prolactin inhibits LH secretion, can't ovulate or have periods and get galactorrhea (milky nipple discharge)
In men presents later, get depression, low testosterone and symptoms due to the mass itself
216
What are non functional prolactinomas?
Not a screwing tumour, blocks stalk and prevents dopamine inhibition of prolactin inhibiting hormone. Need surgery. May secrete inactive LH FSH ACTH
Climactic features due to low hormones or mass effect not prolactin
<5000 prolactin is non functional
217
What are the complications of acromegaly and tests?
CV disease, colonic and thyroid cancer, hypertension, diabetes, sleep apnea headaches, dental problems, snoring, deep voice, carpal tunnel
Do oral glucose tolerance test and IGF1 level monitoring
218
What treatments are there for acromegaly?
```
Surgical tumour removal
Dopamine agonist
Somatostatin analogue
GH receptor blocker
Can use radiotherapy
```
219
What is Cushing disease and what are the signs and symptoms?
ACTH secreting pituitary tumour.
Pink face, round abdomen, skinny weak arms and legs, striae on abdomen, increase bp, diabetes, osteoporosis.
Cushing syndrome is different pathology such as adrenal or steroid mediated
220
What is cranial and nephrogenic diabetes insipidus?
Posterior pituitary secretes ADH, acts on aquaporin, increased water loss. In cranial pituitary disease causes ADH deficiency (inflammation, infiltration, malignancy, infection)
In nephrogenic kidney is resistant to ADH
Unusual to get DI in standard pituitary tumours as normally affect AP
Consequences are dehydration, hypernatraemia, reduced consciousness and death
Treatment synthetic ADH, desmopresin
221
What is pituitary apoplexy and how would someone present?
Vascular event that leads to a stroke, can be tumour haemorrhage or infarction
```
Get sudden headache
Double vision
Cranial nerve palsy
Visual loss
Hypopituitarism
```
