haematology 2 Flashcards
what are globular proteins
- spherical compact proteins
- most water soluble forming colloids (suspension)
what are the different between fibrous and globular proteins
fibrous - long and narrow, structure support, most insoluble, repetitive amino acid sequence, less sensitive to change in heat and pH
globular - round/ spherical, catalysts and transport, most soluble, irregular amino acid sequence, more sensitive to changes in heat and pH
what is the structure of haemoglobin
- tetrametric proteins each with a haem group
- subunits interact through hydrogen and ionic bonds
what is the function of haemoglobin
- transports oxygen in red blood cells by nitrogenous, iron containing pigments - haem groups
what is the 3 groups of haemoglobin
- HbA
-HbA2 - HbF
where is HbA found and what is its formation
- major in adult
- > 97%
- 2 x alpha chains
- 2 x beta chains
where is HbA2 found and what is its formation
- minor in adults
- 1-3%
- 2x alpha chains
- 2 x delta chains
where is HbF found and what is its formation
- fetal
- 2 x alpha chains
- 2 x gamma chains
where is myoglobin only found
- muscle tissue
what is the function of myoglobin
- short term storage of oxygen for muscular contractions
what is the structure of myoglobin
- monomeric protein with high affinity for oxygen
- 153 amino acids with highly bound haem groups
what is the content, capacity and saturation of oxygen
content - quality of oxygen sample
capacity - maximum quantity of oxygen that can combine with haemoglobin in given sample
saturation - ratio of oxygen content: capacity in a given sample
what is the equation for working out percentage saturation
[O2Hb]/ [O2HB] [HHb]
what is oxyhaemoglobins struture
- combining 4 O2 with haem groups
- produce blood red colour
- reversible binding of O2
what happens to oxyhaemoglobin at low oxygen concentration
dissociates to deoxyhaemoglobin and releases oxygen
- darker deep purple
what is partial pressure measured by
- kPa or mmHg
what happens at high and low partial pressure
high - in alveolar capillaries of the lungs, O2 and Hb combine to form O2Hb
low - O2 dissociates from Hb and diffuses down concentration gradient into cells via interstitial space
what is the conformational changes of haemoglobin
- O2 binding breaks ionic bonds and forms new hydrogen bonds relaxing the quaternary protein structure
- increases O2 affinity of remaining hem groups
- positive co-operativity
why is myoglobin not positive co-operativie
- only 1 globular chain
describe the Hb standard curve
- sigmoidal
- tissue with high partial pressure, O2 readily associates with Hb due to positive co-operativity
- lower partial pressure than alveolar blood, rapid dissociation of O2 from Hb
why is positive co-operativity efficient
- allows rapid delivery of 02 to tissue
- without an 81-fold increase in partial pressure would raise O2 saturation from 10 to 90%
what is the 02 binding affinity of Hb affected by
- temperature
- pH
- partial pressure of carbon dioxide
- metabolites
what is the definition of le chateliers Principe
- a system in dynamic equilibrium responds to stress by restoring the equilibrium
what is the chloride shift
HCO3- diffuses out of RBC; Cl- diffuses in to balance charge
what is formed when CO2 reacts with H2O in RBC
carbonic acid
when does the bohr shift occur in the blood
- when CO2 in the blood helps release O2 from O2Hb
how does pH buffering in the blood help
allows large quantities of HCO3- to be transported in the blood without major changes in pH.
what is carbaminohaemoglobin
when a small amount of CO2 is transported by Hb
what does the Bohr shift do to the saturation curve of O2
right shift
what does an increase in partial pressure of venous capillaries cause
- decreases the affinity of Hb for O2
- right shift in ligand saturation curve
where does carbon monied bind
- ferrous iron group in Hb and myoglobin with a 200x affinity compared to oxygen
- competitive antagonism
what are the symptoms of carbon monoxide poisoning
- headache, dizziness, nausea, confusing, fainting
when is glycerine Hb formed
- when glucose binds to HbA1
- irreversible glycosilation of beta chain n terminal of proline
what are the levels of HbA1C
<42 - non diabetic
42-47 - prediabeties
>48 type 2 diabetes
what causes cyanide poising
- smoke inhalation from burning house materials
- fruit stones
- inhalation of hydrocyanic acid
what are the symptoms of cyanide poising and what causes them
- inhibitor of cytochrome C oxidase, impairing oxidative phosphorylation
- coma, seizure, cardiac arrest, weakness, paralysis, nerve lesions
what is the treatment for cyanide poising and how does it work
- amyl nitride
- promotes formation of methemoglobin which CN has a high affinity for
- forms cyanomethemoglobin which slowly releases CN from RBC which can be metabolised by hepatic enzymes
what is methemoglobin
- has a ferric haem group - Fe3+
when is methemoglobin formed
- exposure to environmental agents that oxidise Hb
- germline mutations causing oxidation of Hb
- reduces O2 carrying capacity because Fe3+ cannot reversibly bind to oxygen
when is 2,3BPG made
- by red blood cells during glycolysis
what does 2,3-BPG do
- facilitates efficient transport of oxygen without it Hb would only release 8% to tissue
where is 2,3-BPG found in Hb
- 1 molecule binds to centre pocket of Hb only when in T form
what are the differences between fetal Hb and adult Hb
- 72% similarity in amino acid sequence
- reduced affinity for 2,3-BPG in fetal so affinity for O2 is higher
- difference between affinity between fetal and maternal allows efficient transfer from maternal to verbal RBC via the placenta
what happens to the Hb curve when an allosteric effector is added
- shifts right due to a decrease O2 affinity of Hb
