Week 3 Flashcards
What is critical appraisal?
The process of assessing the outcome of scientific research to judge its trustworthiness, value and relevance
What does critical apprasial include?
Looking for potential bias
Checking relevance of research results to your specific context
Making judgements about value e.g. benefit/cost
What is evidence-based medicine?
The integration of best research evidence with clinical expertise and patient values
What are the 5 steps of evidence based medicine?
- ask a focused question
- find best evidence to answer question
- critically apprasie evidence for validity
- integrate research with clinical expertise and patients values/beliefs/circumstances
- evaluate process
What is the 5 a’s in cycle of enquiry?
Ask: forumulate clinical question
Acquire: search for evidence
Appraise: appraise evidence
Apply: incorporate evidence into decision making
Assess: evaluate process
What is the composition of blood?
55% plasma
45% erythrocytes
<1% wbcs and platelets
What is plasma composed of?
92% water
8% proteins, antibodies, electrolytes
Functions of plasma?
- collects waste around body from tissues and takes to kidneys for excretion
- maintains body temperature
- albumin: maintains osmotic pressure
- fibrinogen: important clotting factor component
- antibodies fight infection
- electrolytes maintain blood pH
Functions of blood?
- delivers substances around the body (oxyegn, water, nutrients)
- removes waste (co2, excess salt and water, debris from dead cells)
- containes wbc to fight infection
- contains clotting factors
- transports hormones from endocrine system (adrenaline, melatonin, insulin, testosterone)
Purpose of RBC being biconcave?
Allows elasticity to fit through capillaries
Function of RBCs?
Gas exchange - transports oxygen around the body via hemoglobin and carries carbon dioxide to lungs to be expelled
How long do RBCs live?
120 days
Where are RBCs broken down?
Spleen/liver
Where do all blood cells stem from?
Pluripotent hamatopoietic stem cell
Where are pluripotent hamatopoietic stem cells produced?
Bone marrow
Function of thrombopoietin?
Hormone growth factir increasing platelet production
Function of erythropoietin?
Hormone growth factor increasing erythrocyte production, low oxygen conc triggers increased EPO
2 qualities of pluripotent stem cells?
Self renew and proliferate/differentiate into progenitor cells
What would the first aid procedure be for a bleeding wound?
- Wear gloves
- apply pressure with dressing and bandage
- remove clothes covering wound
- dont pull objects out of wound
- lie patient down to prevent shock and cover with blanket
What is the triage system?
Categorisation of sick/wounded people
red = immediate
orange = very urgent 10-15 min
yellow = urgent 60 min
green = standard
blue = no danger
What are anticoagulants?
compounds that prevent blood clotting
What are clotting factors?
enzymes/proteins required for clot formation
What is coagulation?
The conversion of liquid blood to a gel like solid
What is haemostasis?
The stopping of bleeding
What are proteases?
Enzymes that break down proteins
What is proteolysis?
Cleavage of peptide bonds in proteins
What is thrombin?
An enzyme that forms clots
What is thrombosis?
Formation of a blood clot
What is a thrombus?
A blood clot
What are the three phases of haemostasis?
- vasoconstriction
-formation of platelet plug - coagulation
What is haemophilia?
patients lack a clotting factor and cannot form a blood clot
Function of sodium citrate?
Prevents blood coagulation in storage
Difference between in vivo and in vitro?
In vivo: in glass
In vitro: living subjects
What is the extrinsic clotting pathway initiated by?
Damaged tissue - tissue factor (III) exposed to blood
What is the extrinsic clotting pathway tested by?
Prothrombin time (PT)
What is the intrinsic clotting pathway activated by?
Activated platelets
What is the intrinsic and final clotting pathway tested by?
Activate partial thromboplastin time APTT
How is the intial clotting response amplified?
Stepwise activation of coagulation factors
Which three things are required for both clotting pathways?
Calcium ions
Clotting factors
Negatively charged phospholipid surfaces of platelets
What are stem cells?
Unspecialised cells which can renew indefinitely and can differentiate into specialised cells
What are two common traits of stem cells?
Self renewal and differentiation capabilities
What is differentiation?
Process of unspecialised cells e.g. stem cells acquire specialised structural/functional features that characterise the cells, tissues or organs of an organism
Which type of cell division do stem cells undergo?
Asymmetric producing 2 dissimilar daughter cells
What are the two types of stem cells produced from stem cell division?
Identical daughter cell maintaining stem cell line
Different daughter cell with different genetic instructions and reduced proliferative capacity
What do the non identical daughter cells of stem cells become?
Progenitor cells: commit to producing one/few terminally differentiated cells e.g. neutrons, muscle cells
What is cell potency?
Cells ability to differentiate into other cell types
What is the hierarchy of stem cell potency?
Totipotent, pluripotent, multipotent, unipotent
Describe totipotent cells?
Can give rise to embryonic membrane and any cell type of adult body e.g. zygote/morula
Describe pluripotent cells?
Can give rise to any cell type of adult body e.g. ICM of blastocyst
Describe multipotent cells?
Can give rise to tissue specific cell types of adult body e.g. mesenchymal or neural stem cells
Describe unipotent cells?
Can give rise to one specific type of adult body tissue cells e.g. skin cells
Which diseases can haematopoietic stem cells transplantations treat?
Leukaemia and myeloma
What cells can mesenchymal stem cells produce?
Adipocyte, chondrocyte, osteocyte
What are induced pluripotent stem cells?
Adult somatic stem cells reprogrammed back to pluripotency so they can differentiate into other cell types
What qualities do iPSCs have?
Self renewal capability
Differentiation potential
Ability to be cultured (grown in lab)
ability to form all germ layers
Where are human embryonic stem cells derived from and what are they used for?
ICM of blastocyst
IVF
What are somatic stem cells?
Non reproductive cells e.g. sperm/eggs that replenish and regenerate dying/damaged cells
Examples of somatic stem cells?
Mesenchymal and haematopoeitic stem cells
Where are haematopoietic stem cells produced?
Femur and pelvic bone marrow
How are iPSCs made?
Treated with transcription factors to switch genes back on to induce pluripotency
Some properties of cancer stem cells?
Characteristics of stem and cancer cells
Can self renew and differetiate
Seed tutors when transplanted into host
Issue with cancer stem cells?
Isn’t killed by traditional cancer therpay
Has to have cancer stem cell targeted therapy
Potential uses of stem cells?
Regenerative medicine
Tissue repair
Drug screening
What is regenerative medicine?
Reapir/replace damaged or diseased human cells or tissue to restore normal function
What is stem cell therapy and who can donate?
Bone marrow transplant to treat blood disorders e.g. leukaemia
Autologous or allogenic transplant from individual with same tissue type e.g. family members
What happens in stem cell therapy?
- blood stem cells removed from donor
- patient treated to remove defective stem cells
-patient injected with donors blood stem cells to produce all blood cells needed throughout their lifetime
What does allogenic mean?
Transported to current location from else wherw
What does autologous mean?
Obtained from same individual
Supine vs prone position?
Supine: lying upwards
Prone: lying downwards (back dissection)
Ventral vs dorsal?
Ventral: belly
Dorsal: back e.g. dorsal fin
3 anatomical planes?
Median: r and l halfs
Frontal: front and back
Transverse: top and bottom halfs
What is a longitudinal section?
Section through length of median plane e.g. leg
What is circumduction?
flexion, abduction, extension, adduction
What is plantar and dorsal?
Plantar: sole of foot
Dorsal: top of foot
Clinical relevance of APTT?
Determines how fast or slow clotting is taking place, determines if people are missing clotting factors etc.
Determines if treatment for blood clot is working
What are the functions of platelets and how long do they live?
Initiate hemostasis when damage to blood vessels occurs
5-9 days
no nucleus
Where are platelets broken down?
spleen
Why is the intrinsic pathway required in blood clotting?
To form clots of a sufficient size
Is clot lysis or formation slower?
Clot lysis
What are the 3 steps of hemostasis briefly?
- vasoconstriction occurs to reduce blood flow
- platelet plug formed
- coagulation cascade
Which 2 things promote platelet adherence and activation in injury?
Exposure of Von Willebrand factor and collage in sub endothelial layer
What allows more platelets to migrate to site in hemostasis?
Platelets secrete granules to recruit more platelets
How is factor X activated in extrinsic pathway?
tissue factor (III) is bound with Calcium and turns Factor VII to factor VIIa
Which factors are required to activate factor X in the intrinsic pathway?
IXa
Calcium
VIII
What activates factor VIII in intrinsic pathway?
Thrombin
What happens in final common pathway of coagulation?
prothrombin converted to thrombin by factor X
thrombin converts soluble fibrinogen to insoluble fibrin
fibrin cross links to form a hard clot from a soft clot with XIIIa
How does plasmin lyse clots?
tPA coverts plasminogen to plasmin
What is shock?
A life threatening form of acute circulatory failure with inadequate oxygen delivery
What happens if shock is left untreated?
Multiple organ dysfunction
End organ damage
Death
How can you recognise shock?
Clinical parameters e.g. HR, BP, RR, GCS
SOFA scoring
Specific symptoms e.g. fever, bleeding
Lactate always elevated
Four types of shock?
Obstructive
Distributive
Cardiogenic
Hypovolemic
What is distributive shock and what can it be caused by?
Severe peripheral dilation = decreased blood pressure so blood isnt supplied to vital organs
Sepsis: toxic effect of inflammatory response, cytokine release causes vasodilation
Anaphalaxis: release of biochemical mediators e.g. histamine causes vasodilation
What is hypovolaemic shock and what can it be caused by?
Significant blood and fluid loss of body
Trauma/GI bleeding/dehydration (stomach ulcers)
Burns
What is cardiogenic shock and what can it be caused by?
Pump failure
Myocardial infarction (heart attack)
Arrythmias
What is obstructive shock and what can it be caused by?
Barriers to cardiac flow/filling
Pulmonary embolism (pulmonary artery blocked by blood clot)
Cardiac tamponade (blood in pericardium)
Tension pneumothorax (air buildup in pleural space causing lung collapse)
How can you treat disributive shock?
Fluid
Vasopressors - constricts blood vessels to inc pressure
Antibiotics
How can you treat hypovolemic shock?
Fluid/blood
How can you treat cardiogenic shock?
Vasopressors, inotropes, fluids
How can you treat OBSTRUCTIVE shock?
Improve circulation
Needle
Thrombolysis - breakdown of blood clots
What increases and what decreases in shock?
Inc: HR, RR
Dec: BP, organ function, GCS, urine output
What are the stages of shock?
Intravascular volume loss
Decreased cardiac output
Impaired tissue oxygenation
End organ dysfunction
Death
How to calculate cardiac output?
CO = HR x SV
What is blood shunting?
Blood is taken from visceral non essential areas to provide heart with enough blood to perfuse vital organs
What happens if you leave a blood shunt for a long time?
Kidneys, liver and bowel begin to fail
What happens in blood loss?
All components lost equally
Oxygen carrying ability and clotting ability impaired
What is the vicious cycle of blood loss?
Increased lactic acid in blood = acidosis
Decreased heart performance = hypothermia
Decreased coagulation = blood clotting issues
(Acidic environemnt affects blood clotting ability)
What is CABCDE in emergency treatment?
Catastrophic haemorrhage control
Airway with C-spine control
Breathing with oxygenation
Circulation with haemmorrhage control
Disability
Exposure
Two methods of opening airway?
Adjuncts
Intubation
Three breathing complications in trauma?
Haemopneumothorax
Fractures
Cardiac tamponade
How can you stop bleeding in trauma
Pressure, tourniquet, elevate
Pelvic binder
Suture
What is an abrasion injury?
Dragging against irregular surface
How to treat abrasion injury?
Clean debris
Dress
Usually no bleeding
What is a laceration injury?
Tearing/splitting of skin caused by blunt force trauma
Irregular levels of depth
How to treat laceration injury?
Irrigate/clean
Close with glue, staples, sutures
What is an incision wound?
Sharp/penetrating trauma
Slash/stab
Clean edges
What should you be cautious of in incision wounds?
Depth and underlying damage
What is a degloving injury?
Skin and blood supply are torn off - major trauma in limbs/digits usually
How do you treat bite wounds?
Antibiotics, tetanus, vaccines
Irrigation, delayed closure/non closure
What should you be aware of in bite wounds?
HPV viruses
Cat bites are very prone to infection
What bacteria is associated with bite wounds?
Pasturella
What is the genome?
All of the genetic information in a cell (DNA)
What is the transcriptome?
All mRNA both coding and non coding expressed by a cell.
What is the proteome?
The complete set of proteins expressed by an organism
Which biological processes are proteins part of?
Enzymes
Antibodies
Growth factors
Muscle
Breathing
What three RNA species are needed to assemble a protein?
Ribosomal rRNA
Transfer RNA tRNA
messenger RNA mRNA
Three steps of protein assembly?
Initiation: AUG start codon initiates translation, tRNA attaches to mRNA
Elongation: addition of more amino acids to transcript
Termination: stop codon stops trabslation
What do free ribosomes synthesise?
Soluble intracellular proteins
How many amino acids are there?
20
How many bases are in one codon?
3
How many amino acids can be made from one base pair and two base pairs?
One: 4
two: 16
three: 64
What is the start codon called?
AUG
What are the stop codons?
UAA, UAG, UGA
How do proteins protect against mutation?
Each amino acid can be made by different combinations of amino acids e.g. UGA, UGG both make same (degeneracy)
Function of R in amino acid?
Variable chemical group which gives amino acids their specific properties
Determines structure and function of proteins and electrical charge of the molecule
Where are proteins R groups found in polar molecules?
Surface as they are hydrophilic
Where are proteins R groups found in non polar molecules?
Buried in hydrophobic interior out of water
How do amino acids link up?
Condensation reaction
What is glycosylation?
Addition of sugar molecule to protein, affects orientation
What is phosphorylation?
Addition of phosphate group, done by kinases, affects receptor signalling/enzyme function
What is an example of a protein activated by proteolysis?
Chymotripsinogen to chymotrypsin by proteolytic enzymes
What is chymotrypsin?
digestive enzyme
What is the primary structure of a protein?
Amino acid sequence
What is the secondary structure of a protein?
Amino acids folded into alpha helices and beta pleated sheets
What is the tertiary structure of a protein?
Folding of protein into their final shape
What is the quaternary structure of a protein?
Coming together of subunits to form overall functional protein complex e.g. haemoglobin
What is the mutation in sickle cell anaemia? What happens to haemoglobin?
Beta globin gene mutation
GAG to GTG at 6th codon
Changes shape/conformation
What does CFTR regulate?
Mucus transport in lungs/pancreas
What is cystic fibrosis caused by?
Genetic mutation in CFTR (chloride ion channel)
Examples of mutations?
Nonsense/deletion
Deletion causing protein misfolding
Premature degregation
Substutiton
Examples of proteins in therapy?
Recombitant proteins e.g. insulin
Antibodies
Peptide mimetics
Blockers of protein function
Where is erythropoietin produced?
Kidney
Where do platelets adhere?
Exposed collagen on injured vessel wall
How does sodium citrate prevent coagulation?
Bind to calcium in blood which prevents calcium regulating binding
Which vitamin is cruical for synthesising coagulation factors and associated with the liver?
Vitamin K
What is von willebrand disease?
Lack of von willebrand factor which is required for platelet adhesion and activating factor VIII
What would APTT and PT be in someone with von willebrand disease?
APTT prolonged
PT normal
What does a functional haemogloibn molecule contain?
4 haem groups
4 polypeptide chains
Where is the site of synthesis of coagulation factors?
Liver
What is the APTT and PT in someone with end stage liver failure?
Both prolonged
What is haemophilia A?
Low clotting factor VIII
What is haemophilia b?
Low clotting factor IX
Function of citrate in sodium citrate?
Chelates calcium ions required for activation of clotting factors
Rapidly metabolised
What factors are the final common pathway?
Conversion of X to Xa
What is used to treat haemophilia?
Factor VIII transfusion
Why is plasma a mixture from multiple donors?
Individual clotting times vary so it allows an average clotting time to be observed
What shape do platelets change to when activated?
Spherical to finger like projections
What charges does heparin carry
Negative
Which protein is missing from serum which is in plasma?
Fibrinogen
Which type of molecule is trypsin?
Endopeptidase
Which enzymes do streptococci produce?
streptokinase
What is streptokinase simalar to?
urokinase
tissue plasminogen activator (tPA)
Function of streptokinase?
Can convert inactive plasminogen to activwe plasmin
Which pathways does heparin inhibit?
Intrinsic and common
Why are clots usually red when formed?
RBCs are trapped
Which test would warfarin affect?
pt time due to vit k dependent anticoagulation factors in extrinsic pathway
Which type of drugs are heparin and warfarin?
Anticoagulants
Which factor is thrombin?
IIa
Which factors are required to activate X in intrinsic pathway?
VIII and IXa
What activates VIII in intrinsic pathway?
Thrombin
What are the factors in the final common pathway?
Xa and V
Which protein is mutated in sickle cell anaemia?
Globin
Where is plasminogen found in blood?
Plasma
What happens when calcium is replaced with cheleated calcium in clotting?
Clotting doesnt occur as cheleated has citrate
Which molecule is a zymogen?
Prothrombin
What is a zymogen?
Inactive substance converted to enzyme when activated by an enzyme
Function of alteplase?
Converts plasminogen to plasmin
Function of transexamic acid?
Binds to plasminogen decreasing fibrinolysis
Prevents excessive blood loss
Which condition would be red aka immediate in triage system?
cardiac arrest/multiple injuries
Which condition would be organge aka very urgent in triage system?
hypoglycaemia, cardiac chest pain
Which condition would be yellow aka very urgent in triage system?
eye injury, poisoning, abdominal pain
Which condition would be green aka standard in triage system?
Insect bite, sprained ankle
Which condition would be blue aka non urgent in triage system?
Long term symtoms, non acute rashes
How is trypsin relevant to blood coagulation?
Cleaves part of prothrombin to form thrombin
Function of prothrombinase, what factor is thus?
Cleaves part of prothrombin to form thrombin
Factor X
What is endocytosis?
Cell engulfing material using membrane
What is exocytosis?
Release of a substance via vesicles where the vesicular membrane fuses with the plasma membrane and releases the molecule
Describe class I hemorrhagic shock
Up to 750ml blood loss
up to 15% total blood
pulse <100
normal BP
resp rate 14-20
urine output >30 mls/hr
normal mental statis
Describe class II haemmorrhagic shock
750-1500ml blood loss
up to 15-30% total blood
pulse >100
normal BP
resp rate 20-30
urine output 20-30 mls/hr
mild anxiety
Describe class III haemmorrhagic shock
1500-2000ml blood loss
up to 30-40% total blood
pulse >120
decreased BP
resp rate 30-40
urine output 5-15 mls/hr
anxiety
Describe class IV haemmorrhagic shock
> 2000ml blood loss
40% total blood
pulse >140
decreased BP
resp rate >40
urine output negligible
confusion