Download All of medicine in 12 hours…

All of medicine in 12 hours…
Dr. Alan McLeod (F2)
The Plan
Day One
Day Two
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A systematic approach
Chest Pain
Acute sob
Chronic sob
Haemoptysis
TATT
Painful Limb
Breast Pain
Emergency management
Maximising your marks
Swallowing
Change in bowel habits
Hepatomegaly
Abdo pain
Pregnancy / Birth
Recurrent Infections
Headache
Stroke
Pharmacology basics
2 Minutes
10 Causes of Chest Pain
Puzzled?
You Need A SYSTEM…
Puzzled?
What do I do?
I GET VINO…
I
G
E
T
V
I
N
O
Infectious / inflammatory
Genetic / Idiopathic
Endocrine
Trauma
Vascular
Iatrogenic / ingested
Neoplastic
Organs
2 Minutes
10 Causes of Chest Pain
Chest Pain? Where’s that
wine…
I
G
E
T
Infectious / inflammatory Pneumonia, pleurisy, Costochonditis
Trauma
Fractured rib, pulled muscle, pneumothorax
V
Vascular
Myocardial infarction, angina, aortic
dissection, PE
I
N
Iatrogenic / ingested
Surgical scar
Neoplastic
Bony mets
Organs / other
Oesophagus (spasm, reflux), heart
(pericarditis)
Lung, Aorta, bones, muscle, cartilege,
anxiety
O
Genetic / ideopathic
Endocrine
Ischaemic Heart Disease
• Approx 1/3rd of all
male deaths
• Approx ¼ of all
female deaths
• Atheroma of coronary
vessels
Right: Right Ventricle, most of Right Atrium, Part of Left Atrium
Left: Left Ventricle, part of Right atrium, most of Left atrium
Left circumflex: Left margin of heart and its entire posterior wall, Left
atrium, posterior IV septum
LAD: Anterior 2/3 of IV septum, anterior portion of LV, whole apex
SA Node: Right 51-65%, Left 35-45%, Bilateral <10%
AV Node: Right 80-90%, Left 10-20%
ALL HIGHLY VARIABLE!!!
Coronary Arteries:
Fill During DIASTOLE
Arterial Disease
Arteriosclerosis
• Thickening and
hardening of wall
– Reduced lumen
– Reduced flow
– Reduced elasticity
– Reduced contrractility
• Diabetes
• Hypertension
Atherosclerosis
• Commonest cause of
arteriosclerosis
• Specific disease
• Tunica intima
• Mostly large and
medium vessels
• Small in prolonged
systemic
hypertension
Atherosclerosis
• Changes in intima 
Smaller vessel
thrombus formation
atherosclerosis
• Reduced lumenal size • Ischaemic heart
disease
– Poor
perfusion/hypoxia
• Most strokes
– Tissue death
• Peripheral heart
• Loss of elasticity
disease
– Aneurysm formation
Plaque Formation
Plaque Formation
Plaque Formation
Plaque Formation
Plaque Anatomy
Plaque Anatomy (early)
• Free Lipid
• Foam cells
• Increased myointimal
cells
• Collagen
• Disruption of internal
elastic lamina
Plaque Anatomy (later)
• Collagen cap
• Extracellular lipid mass
• Foam cells
• Myointimal cells
• Disrupted internal elastic
lamina
• Pressure atrophy of
muscle  collagenous
replacement
Atheroma – Risk factors
Non-preventable
• Increasing age
• Male sex
• Family history
Preventable
• Hyperlipidaemia
– LDL and Cholesterol
• Hypertension
– Diastolic most
important
• Diabetes
• Smoking
Fibrous
Pericardium
Pericardial
Space
Fold
Myocardium
Layers of the Heart
Endocardium
Parietal Layer of
Serous Pericardium
Visceral Layer of
Serous Pericardium
Compare Skeletal and
Cardiac Muscle
Muscle Comparison
Skeletal
Cardiac
Smooth
Voluntary
Involuntary
Involuntary
Striated
Striated
Non-striated
Multinucleated
Mononucleated
Mononucleated
Unbranched
Branched
Unbranched
No gap junctions
Gap junctions
No gap junctions
Myocyte Action
Potential
Phase Ion
Voltage
0
Na+ IN
1
K+ OUT -ve
2
Ca++ IN
Steady
+
K OUT
3
K+ OUT -ve
4
K+ OUT -ve (slow)
+ve (rapid)
NAK-CAKKK
In Detail
Membrane potential (mV)
Pacemaker Action Potential
0
Ca++ In
-40
-80
K+ Out
Comparison of action potentials
Pacemaker cell
Myocyte
Slow diastolic repolarisation
in phase 4
Pot. Approx -65 to -40mV
Constant phase 4 (resting)
potential
Resting Pot. approx -90 mV
Phase 0 less steep
Phase 0 via slow channels
Phase 0 more steep
Phase 0 via fast Na
channels
Plateau not sustained
Plateau sustained
Repolarisation more gradual Repolarisation less gradual
Excitation-contraction coupling
• Electrical signal
• In The Heart
• Stimulates contraction • Calcium induced
calcium release
• Act Pot from SA Node
Generally
• Signal causes
depolarisation
• CA++ entry results
• Causing contraction
Excitation-contraction coupling
SAN
Excitation
L Type Calcium Channel
Ca++
Ca++ Ca++
Ca++
Ca++
Ca++
SR Ca
Ca++
Ca++
Ca++
++
Excitation-contraction coupling
L Type Calcium Channel
Ca++
Ca++ Ca++
Ca++
Ryanodine Receptor
Ca++
Ca++
SR Ca
Ca++
Ca++
Ca++
++
Excitation-contraction coupling
L Type Calcium Channel
Ca++
Ca++ Ca++
Ca++
Ryanodine Receptor
Ca++
Ca++
SR Ca
Ca++
Ca++
Ca++
++
Excitation-contraction coupling
Ca++
Ca++
Tropomysin
Ca++
Ca++
SR
Ca++
Ca++
Ca++
Ca++
Ca++
Excitation-contraction coupling
Ca++
Ca++
Tropomysin
Ca++
Ca++
SR
Ca++
Ca++
Ca++
Ca++
Ca++
Excitation-contraction coupling
Ca++
Ca++ Ca++ Ca++
Tropomysin ++
Ca
Ca++ Ca++ Ca++
Contraction
CA++
SR
Describe Sliding Filament
Theory
Sliding Filament Theory
http://uk.youtube.com/w
atch?v=gJ309LfHQ3M&
feature=related
• Calcium enters
• Binding sites on actin
uncovered by movement of
Tropomyosin / troponin
complex
• Myosin binds to site 
powerstroke
• ATP binds to myosin 
release from binding
• ATP  ADP + Pi – cocks
myosin for another
Powerstroke
• Continues as long as ATP
and Ca present
Sliding Filament Theory
Normal Lead 2
A Segment is
Shorter
than an
interval
The Normal ECG
PR interval: first deflection of P  first
deflection of QRS
– 120-200 ms (3-5 small sq)
QRS interval: first deflection of QRS  end
of last deflection
– <100 ms (<3 small sq)
QT interval (QTc is QT corrected for heart
rate). Start of QRS  end of T wave
– 360-440 ms (<11 small sq)
Additional Abnormalities
• Pathological Q wave
– Duration > 1 small sq
• ST Depression
– 1mm or more over
isoelectric line
• ST Elevation
– 0.5mm or more below
isoelectric line
• T wave abnormality
– Normally upright in I, II
& V1 – V3
– Normally inverted in
aVr
– Variable in others
STEMI and NSTEMI
STEMI
• ST Elevation MI
NSTEMI
• Non ST Elevation MI
• ST elevation on ECG
• Positive enzyme tests
• No ST elevation
• Positive enzyme tests
STEMI and NSTEMI
ST Segment
A
I
P
T
A: Normal ECG
B: ST Elevation
C: ST Depression
QRS
B
C
ST elevation in
response to
Isoelectric line (I)
Evolution of ECG Changes in
STEMI
• Minutes to hours
– Peaked T waves
• Hours
– ST elevation
• Hours to days
– T wave inversion
– Loss of R wave
• Days
– Pathological Q wave
Cardiac Enzymes
Fibrinolysis
• tPa
• Streptokinase
ACS? GO CARDIO ABCD
G
GTN
O
Oxygen
C
Clot prevention - enoxaparin
A
Aspirin ± clopidogrel
R
Raised position
D
Diamorphine + antiemetic
I
Investigate: ECG, enzymes, Troponin, CXR
O
Observe: Repeat ECG + Basic obs,
A
ACE inhibitor within 24 hours
B
Beta blocker
C
Cholesterol - statin
D
Diabetic control – tight control for at least 24 hours
2 Minutes
5 Causes of acute Dyspnoea
Acute Dyspnoea? Need alcohol!
I
G
E
T
V
I
N
O
Infectious / inflammatory
Asthma, Pneumonia, COPD exacerbation
(e.g. upper resp tract infection)
Genetic / ideopathic
Endocrine
Trauma
Pneumothorax
Vascular
Myocardial infarction, PE
Iatrogenic / ingested
Foreign body (mostly children)
Neoplastic
Organs / other
Lungs
Lung Anatomy
Cupular
Mediastinal
Costal
2 Lobes
3 Lobes
Diaphragmatic
The Alveolus
Muscles of Breathing
Diaphragm
• Phrenic nerve C3,4 & 5
Intercostal muscles
• External
• Internal
Compare the bronchial and
pulmonary arteries
Vessels in the Lung
• Pulmonary Artery
–
–
–
–
Deoxygenated blood
From Right Ventricle
Oxygenated in lungs
Affected in PE
• Bronchial Artery
– Oxygenated blood
– From systemic supply
– Supplies tissues of
lung
• Pulmonary vein
– Oxygenated blood
– From lungs
– To Left atrium
Velocity and Flow
Velocity
• Displacement of single
particle per unit time
• Inversely proportional to
cross sectional area
– Faster in thinner tubes
• Aorta is thinner than total
mass of capillaries
– V slow capillary flow
– Time for gaseous exch
Flow
• Volume of fluid passing
point A at time B
• Proportional to pressure
difference
• Inversely proportional to
tube length
• Proportional to r4
• Inversely proportional to
viscosity
Resistance (R)
In Parallel:
1/RTOT = 1/R1 + 1/R2 + 1/R3
In Series: RTOT = R1 + R2 + R3
Resistance may be varied in arteries and arterioles by
control of lumen cross sectional area via smooth muscle
contraction / relaxation
Laminar and Turbulant Flow
Laminar:
• Concentric thin
adjacent layers of
fluid
• ‘Rings within rings’
• Speed max at centre
• Elements stay in one
lamina
Laminar and Turbulant Flow
Turbulant:
• Fluid elements not
contained in one
lamina
• Radial and
circumferential mixing
• Vortex generation
• Pressure needed to
maintain flow is
increased
Venous Thromboembolism
Virchow’s Triad
• Or FECing blood…
– Flow disturbances
• Stasis
• Slow
• turbulant
– Endothelial damage
• E.g. atheroma
• Stasis / turbulance
Genetic Disorders
• Factor V Leiden
– Factor V not
inactivated
• Anticoagulant lack
– Protein C deficiency
– Protein S deficiency
– Antithrombin III defic.
– Coagulability changes
• Genetic
• Oral contraceptive pill
• You may not need to
know these…
Consequences of VTE
PORT
• Propagation
– Grows along vessel
• Organisation
– Granulation tissue
• Recanalisation
– New passages
through granulation
tissue
• Thromboembolism
– E.g PE
Embolism
‘Occlusion of a vessel by a mass of material transported
through the bloodstream’
A Variety of materials
• Thrombus
• Tumour mass
• Fat/ bone marrow
• Amniotic fluid
• Air
A variety of
consequences
• Unstable angina
• Stroke / TIA
• Pulmonary embolism
• Other infarct
• Lower limb muscle
DVT and PE
From Vein to Artery…
• DVT in leg
• Loss of embolus
– Travels in systemic
circ
• Lodges in pulmonary
artery
–
–
–
–
85% Minor PE
10% Major
5% Massive
Rarely recurrent
Major
• Dyspnoea
• Haemoptysis
• Pleuritic chest pain
Minor
• Possibly
assymptomatic
• Dyspnoea
• Pleuritic chest pain
Predisposing Factors
To PE
• Previous PE
• DVT
To DVT
• Immobility
• Post-operative
• Pregnancy / post
partum
• OCP
• Nephrotic syndrome
• Trauma esp severe
burns
• Cardiac failure
Asthma
COS of Three Pathologies
Airway
Constriction
Oedema
Secretions
ABGs - pH
Henderson-Hasselbalch (H-H) equation
pH = 6.1 + log [HCO3-] / pCO2 x 0.23
What are the main factors
measured on an ABG?
What are the Reference Ranges?
Reference Ranges
pH:
pCO2:
pO2:
[HCO3-]:
Base
excess:
7.35 – 7.45
4.7 – 6.0 kPa (about 35-45 mmHg)
>10.6 kPa (>80 mmHg)
22-25 mmol/L*
+/- 2 mmol/L*
* standardised, as if pCO2 were 5.3
ROD: Respiratory cause if
pH and pCO2 move in
Opposite Directions
2 Minutes
5 Causes of Chronic Dyspnoea
Chronic Dyspnoea? Gimme
Wine!
I
G
E
T
V
I
N
Infectious / inflammatory COPD
Neoplastic
Lung Cancer
O
Organs / other
Lungs: fibrosis, pleural effusion
Heart: failure, pericardial effusion
Genetic / ideopathic
Endocrine
Trauma
Vascular
Anaemia
Iatrogenic / ingested
Heart Failure
'failure of heart to pump
blood forwards at a
sufficient rate to meet
metabolic demand'
(forward failure)
'ability to pump
sufficient blood to meet
metabolic demand only
if cardiac filling
pressures are
abnormally high’
(backward demand)
Heart Failure
• Left sided (varied
causes – see right)
• Right sided – caused
by LEFT heart failure
or cor pulmonale
Pathological causes
• Myocardial disease
• Congestive failure –
failure of both left and
right sides
• Pressure overload
– Myocardial infarction
• Volume overload
– Regurgitation
– Arteriovenous shunts
– Hypertension
(including pulmonary
in RHF)
– Stenosis
Define Preload and Afterload
Useful Terms
Preload
• Stretch on myocardial
fibre before
contraction
Afterload
• Ventricular wall
tension during
contraction
– The resistance that
must be overcome
Ejection fraction
• Fraction of end
diastolic volume
ejected from ventricle
during systole
– 55-70% normal
Remember
• CO = SV x HR
List Clinical Features of Right
Heart failure
Heart Failure - Features
L
eft sided
U •Dyspnoea
N •Orthopnoea
G •PND
•Fatigue
R
E •Tachypnoea
L •Haemoptysis
A •Tachycardia
T •Sweating
E
D
R
ight
E
S
T
•Swollen legs
•RUQ discomfort
•Nausea
•Anorexia
sided
O
F •Pitting periph. oedema
•Elevated JVP
B •Hepatomegaly
O
D
Y
Central Venous Pressure
•
•
•
•
Pressure measured in central veins.
Indicates mean right atrial pressure
Frequently used as an estimate of right ventr. preload.
CVP rises with poor right ventr. Function or obstructed
pulmonary circulation.
Measuring CVP
• Central Line
• Catheter placed thorugh subclavian vein
• Invasive
• Alternative is CVP
Measuring CVP
Jugular venous pressure
• Use right internal jugular
vein
• Patient at a 45° angle,
head to the left
• Light source that shines
obliquely from the left
• Locate the anatomical
landmarks
• Locate the JVP
• Measure the level of the
JVP
Anatomical landmarks
• Medial end of clavicle
• To ear lobe
• Under medial aspect of
sternocleidomastoid
• Level is measured from
the sternal angle of Louis
to top of column
JVP
JVP vs Carotid pulse
• The JVP pulse is
• Not palpable
• Obliterated by pressure
• Characterised by a
double waveform
• Varies with respiration decreases with inspiration
• Enhanced by the
hepatojugular reflux
The Hepatojugular Reflux
• Firm pressure is applied
to the right upper
quadrant using the palm
of the hand
• A transient increase in the
JVP will be seen in
normal patients
• There may be a delayed
recovery back to baseline
which is more marked in
right ventricular failure
a
x
c
x’
v
y
Jugular venous waveform
a wave: rise in right atrial
pressure during atrial
contraction
x descent: atrial relaxation + RV
contraction (pulls atrium
downward)
c wave: bowing of tricuspid valve
into RA during systole
v wave: right atrial filling, tricuspid
valve closed
y descent: emptying of right
atrium after tricuspid valve
opens
Starling Curve
Heart has reached
limit of response,
insensitive to further
changes in RAP
Normal physiological range,
high sensitivity to RAP
changes
RAP (mmHg)
• RAP=Right Atrial
Pressure
• CO=Cardiac
Output
• Remember: too
much stretch
reduces ability to
contract… (blue
dashed line)
Vol (ml) Pressure (mmHg)
Flow / Volume Loops
Vol (ml) Pressure (mmHg)
Flow / Volume Loops
280 ms
700 ms
List the common diastolic and
systolic murmurs
A Piratical Crew…
Dire Stolic
Ms ARrrrrr
A Piratical Crew…
DIASTOLIC murmurs are:
MS: Mitral stenosis
AR: Atrial regurg.
MS ARrrrrr…
Systolic?
Meet MR ASs
Sympathetic stimulation
Location
Receptor Type
Action if stimulated
Heart
Beta
Increased HR and contractility
Vasodilatation
Blood vessels in Beta
skeletal muscle
Blood vessels
elsewhere
Alpha
Vasoconstriction
Bronchioles
Beta
Relaxes smooth musc.
Pupil of eye
Salivary glands
Sweat glands
Liver
Beta
Beta
Alpha
Alpha, Beta
Gut Secretion
Gut motility
None
Alpha, Beta
Dilates (darkness)
Little, thicker secr
Promotes sweat
Glycogenolysis
Gluconeogenesis
Inhibits peristalsis
GPCRs
http://uk.youtube.com/watch?v=tOcGbnBCdMM
http://uk.youtube.com/watch?v=bU4955rLv_8&feature=rela
ted
GPCR Summary
• Receptor complex + G
protein
• G Protein has 3
subunits (alpha, beta &
gamma)
• Receptor binds ligand
• Conformational change
• Loss of GDP from G
protein alpha subunit
• Binding of GTP
• Separation of alpha
subunit from betagamma dimer
• Alpha and beta-gamma
freed to interact with
effectors.
• Cascade effect.
• Cycle starts again
GPCRs in the heart
Beta receptors
• GPCRs
• Gs activates adenylate
cyclase
– Increased cAMP
– ATP cAMP
• cAMP activates PKA
• PKA phosphorylates
alpha-1 subunit on
voltage-gated Ca++
channels
• Increased Ca++ influx
• Increased inotropy
• Increased rate
Ca++
In
Beta-adrenergic antagonists
‘Beta blockers’
• Combat the harmful
activation of the
sympathetic nervous
system
• Decrease HR
• Decrease contractility
Examples
• Propranalol
• Sotalol
Side effects
• Bronchoconstriction
• Bradycardia
GPCRs in the lung
Beta receptors
• GPCRs
• Gs actvates
adenylate cyclase
– Increased cAMP
– ATP cAMP
• cAMP causes
relaxation of the
smooth muscle
• Decreases sensitivity
of the IP3 receptor,
decreasing release of
calcium from
intracellular stores in
response to IP31
• Some proponents
argue for a cAMP
independent PKA
mechanism as well2
Parasympathetic stimulation
Location
Action if stimulated
Heart
Decreased HR
Blood vessels in skeletal muscle
-
Blood vessels elsewhere
-
Bronchioles
Pupil of eye
Salivary glands
Sweat glands
Liver
Gut Secretion
Gut motility
Constricts (light)
Abundant watery secr
Glycogen formation
Stimulates
Stim peristalsis
Parasympathetic vs Sympathetic
Long Presynaptic N
ACh
Synapse Near
Target Organ
Parasympathetic
CN 3, 7, 9, 10
S2,3,4
Target
Organ
Synapse Near
CNS Origin
ACh
Sympathetic
T1 – L2
ACh
Long Postsynaptic N
NA
ACE Inhibitors
• In HF the reninangiotensinaldosterone pathway
is activated
inappropriately
– Poor renal perfusion
– Sympathetic activation
(beta receptors)
– Diuretics
Effects
• Reduce vasc.
resitance
– Reduce afterload
– Improve perfusion
• Inhibit aldosterone &
reduce Na+ reabsorp
– Cause naturiuresis
• Proven to prolong life
Heart Failure – ACE Inhibitors
• Reduce ATII
formation
• So reducing Na+
reabsorption
• So reducing water
retention
• So reducing central
venous pressure
• So reducing load
upon heart
TB (or not TB…)
Re-emerging organism
• HIV
• Drug resistance
• Mycobacterium
–
–
–
–
Mycolic acid wax coat
Resistant to drying
Acid fast
Slow growing
Spread:
• Coughed into air
• Remain for hours as
micronuclei
• Bypass cilliary cells
• Enter alveoli
• Enter resident
macrophages
Two disease forms
Primary
Secondary
• 91% no disease
• Reactivation
• 3% progressive
• Damage is from host
systemic leading to
immune response
death
• Remainder pulmonary
or extrapulmonary TB
Tuberculosis
Features
• Shortness of breath
• Fever and sweating,
especially at night
• Haemoptysis
• Loss of appetite
• Weight loss
• Fatigue and tiredness
• Lymphadenopathy
Demographics
• Black African (211 per
100,000)
• Pakistani (145 per
100,000)
• Indian (104 per
100,000)
Diagnosis and Management
Diagnosis
Management
• PPD / Mantoux
• Sputum culture
BCG Vaccine
– Acid Fast Stain (ZN)
• Chest X-ray
• Bronchoscopy ±
biopsy
RIPE
• Rifampicin 6 months
• Isoniazid 6 months
• Pyrazinamide 2
months
• Ethambutol 2 months
What is meant by
‘concordance’
Social Science: Taking the pills…
• Compliance
– Extent to which
patient’s behaviour
matches
recommendations
from the prescriber
• Adherence
– Extent to which the
patient’s behaviour
matches agreed
recommendations
from the prescriber.
• Concordance
– Extent to which the
patient’s behaviour
matches agreed
recommendations
from the prescriber
after exploring and
discussing the
patients beliefs,
views and opinions.
Social Science: Taking the pills…
Poor concordance
• The homeless
• Minority groups
• Learning difficulties
• Dementia
• Psychological illness
• Those with a history
of non-concordance
Increasing concordance
• Directly observed
therapy
• Key workers
• Home visits
• Health education
• Reminder letters
• Foreign lang
materials
2 Minutes
5 Causes of Haemoptysis
Haemoptysis? Where’s that wine…
I
G
E
T
V
I
N
O
Infectious / inflammatory Pulmonary tuberculosis
Genetic / idiopathic
Endocrine
Trauma
Chest trauma
Vascular
Pulmonary embolism
Iatrogenic / ingested
Neoplastic
Bronchial carcinoma
Organs / other
Nose: epistaxis; oesophagus: maller weiss
tear
Lung: bronchiectasis; Heart: mitral stenosis
Lung cancer
• Male: Female 7:1
• Decreasing
• Male peak in 60s
• Female peak in 70s
• Rare under 25 years
Presenting complaints
• 90% symptomatic
–
–
–
–
–
40% Haemoptysis
75% Anorexia
75% Dyspnoea
75% Cough
75% Pain
• Remember Weight Loss
• 10% Incidental imaging
Lung Cancer - Diagnosis
• Imaging
– Plain film
– CT
– MRI
Biopsy
• Peripheral lesions
– Percutaneous biopsy
• Proximal lesions
– Bronchoscopic biopsy
• Cytology
– Sputum
– Bronchoscopic
washings
• Pleural Effusions
– Fine needle aspiration
Lung Cancer
Types
• Small Cell (20-30%)
• Non-small Cell
– Large Cell (10-15%)
– Adenocarcinoma (~20%)
• Commonest non-smoking
– Squamous cell
carcinoma (40-60%)
• Commonest smoking
related
Treatment
• Small cell
– Early metastasis
– Chemotherapy and
radiotherapy first line
• Non-small cell
– Surgery first line
• Lobectomy
• Pneumonectomy
– Radio / chemo as req
Haemostasis
Stops your blood falling
on the floor…
• Vasoconstriction
• Platelet aggregation
• Clotting cascade
Platelets
• Made from
Megakaryocytes
• Last ~10 days
• Do nothing until
activated
• Collagen
• Thromboxane A2
(TXA2)
• Thrombin (from clotting)
• ADP
Platelet Aggregation
Activated Platelets
• Release TXA2
• Change form
• Form plug by adhering to
– Other platelets
– Collagen under epithelium
– Via Von Willibrand’s Factor
• Promote Coagulation
• Prostacyclin and CD39
prevent activation
Clotting
Extrinsic
Intrinsic
Damage to tissue
outside vessel
Damage to the
blood vessel
Common
Factor X
(inactive)
Tissue
Thromboplastin
Clotting cascade
Factor Xa
(active)
Factor II - Prothrombin
(inactive)
Fibrinogen
Factor IIa - Thrombin
(active)
Fibrinogen
Clot
Clotting
Extrinsic
Intrinsic
Damage to tissue
outside vessel
Damage to the
blood vessel
Common
Factor X
(inactive)
Tissue
Thromboplastin
Factor 9
Factor 8
Clotting cascade
Factor Xa
(active)
Factor II - Prothrombin
(inactive)
Fibrinogen
Factor IIa - Thrombin
(active)
Fibrinogen
Clot
Clotting
Extrinsic
Intrinsic
Haemophilia B
Damage to tissue
outside vessel
Damage to the
blood vessel
Common
Factor X
(inactive)
Tissue
Thromboplastin
Factor 9
Factor 8
Clotting cascade
Factor Xa
(active)
Factor II - Prothrombin
(inactive)
Fibrinogen
Haemophilia A
Factor IIa - Thrombin
(active)
Fibrinogen
Clot
Clotting
Extrinsic
Intrinsic
B
Damage to tissue
outside vessel
Damage to the
blood vessel
Common
Factor X
(inactive)
Tissue
Thromboplastin
Factor 9
Factor 8
Clotting cascade
INR / PT
Factor II - Prothrombin
(inactive)
Fibrinogen
Factor Xa
(active)
aPTT (PTT)
A
Factor IIa - Thrombin
(active)
Fibrinogen
Clot
Haemophilia
X-Linked Recessive
What is the role of vitamin K in
blood clotting?
Vitamin K and Warfarin
• Factors 2,7,9 & 10
must be gamma
carboxylated
• Vitamin K is a vital
cofactor
• Warfarin inhibits
enzyme
– Prevents Vitamin K
recycling
Factors
2,7,9 & 10
Gamma
carboxylated
Reduced
Vitamin K
Oxidised
Vitamin K
Vitamin K
Reductase
Vitamin K
-
Vitamin K
Reductase
Warfarin
Vitamin K Dependent Factors
INR / PT
K
K
aPTT (PTT)
K
Intrinsic Pathway
K
Extrinsic Pathway
Common Pathway
ATIII and Unfractionated Heparin
Heparin
IIa
Factor IIa
(Thrombin)
IIa
IIa
*
ATIII
Xa
Factor
Xa
Xa
Xa
*
* Note the change in ATII conformation
ATIII and LMW Heparin
No substrate binding
LMW
Heparin
IIa
IIa
IIa
*
No substrate binding needed
Xa
Factor
Xa
Xa
Xa
*
* Note the change in ATII conformation
ATIII and Heparin - Summary
• Antithrombin III deactivates clotting factors
IIa (thrombin) & Xa
• It does NOT need heparin to do this
• BUT heparin makes it go FASTER
• LMWH only works on Xa
• Longer molecules in unfractionated
heparin work on IIa (thrombin) as well
The Clot
• Platelet activation
• Fibrinogen  fibrin
• Fibrin assembles into
long fibrils
• Platelets + Fibils =
Clot
• RBCs join later
2 Minutes
10 Causes of a Painful Limb
Painful Limb? Time for some
Wine!
I
G
E
Infectious / inflammatory Cellulitis, septic arthritis
Genetic / ideopathic
Osteogenesis imperfecta related fracture
Endocrine
Osteoporosis related fracture
T
Trauma
Fracture, dislocation, pulled muscle,
ligamentous injury
V
I
N
Vascular
Claudication
Iatrogenic / ingested
Corticosteroid  osteoporis  fracture
Neoplastic
Bony mets, Primary bone cancer (rare)
O
Organs / other
Joints: osteoarthritis, rheumatoid arthritis
Nerves: sciatica
Fracture
•
•
•
•
Pain
Swelling
Deformity
Loss of function
• High impact
• Repetitive impact
(stress)
• Pathologic
Fractured Neck of Femur
Blood supply to head
- In order of importance
• Capsular supply
– From Med + Lat
circumflex
– From Deep femoral
• Nutrient artery
– From deep femoral
• Ligamentum teres
– From Medial
epiphyseal
Fractured Neck of Femur
Fractured Neck of Femur
Colles & Smiths Fractures
Colles
• Distal radius
• Dorsal angulation
• FOOSH
• Elderly
• Osteoporosis
Smiths - as above but
• Volar angulation
Scaphoid
fracture
• FOOSH
• Tenderness in
anatomical snuffbox
– Structures of
snuffbox
• Three X-ray views
• Blood supply enters
distally
– Potential avascular
necrosis
Humeral fracture
• Most Commonly at
Surgical neck
– Axillary nerve damage
• Also mid shaft
• If involves radial groove
– Radial nerve damage
• Distal radius uncommon
Humeral fracture
Distal radius uncommon
• Supracondylar
– Median nerve
• Medial epicondyle
– Ulnar Nerve
What is this fracture?
Monteggia and Galleazzi
Fracture-dislocations
Medics
Under
Monteggia (a)
Ulnar shaft
Pressure
Get
Proximal Radioulnar Joint
Galleazzi (b)
Really
Drunk
Radial Shaft
Distal RUJ
Fracture Management
The “Three R’s”
• Reduce
• Retain
– Cast
– Internal fixation
– External fixation
• Rehabilitate
Pulled elbow
• Mostly Children 1-4 yrs
• Dislocation of radial
head from annular
ligament
• 50% have no Hx
• Not using limb
• Extension + pronation
No deformity
In adults Monteggia fracture
dislocation is likely differential
Bone Healing
Mins – 3 days
• Haematoma and
Necrotic tissue
2 days – 2 weeks
• Phagocytosis
• Provisional callus
3 weeks on
• Firm callus
• Mineralisation
Weeks - months
• Remodeling
Factors influencing Healing
Local
Systemic
•
•
•
•
•
•
•
•
•
Tissue damage
Tissue loss
Infection
Foreign body
Patient age
Nutritional status
Smoking / alcohol
Steroids
Systemic illnesses
such as diabetes,
renal, lung, cardiac.
Synovial
Joint
Video Link
Collagen
Synthesis
http://depts.washing
ton.edu/bonebio/AS
BMRed/collagen/col
lagen.swf
Compare and contrast
rheumatoid arthritis with
osteoarthritis
Osteo and Rheumatoid
Osteoarthritis
• Disease of cartilage
• No immune
component
– M=F
– Rheumatoid factor -ve
• Assymetric
• Large > small joints
• DIP Joints
Rheumatoid arthritis
• Disease of synovium
• Autoimmune
– M<F (approx 1 : 3-4)
– Rheumatoid factor
80%
• Symmetrical
• Small > large joints
• MCP + PIP Joints
Septic Arthritis
‘joint inflammation
caused by the presence
of live intra-articular
micro-organisms’
•Acute
•Painful
•Swollen
•Effectively immobile
Risk of rapid joint loss
Management
• Aspirate pus
– Send for analysis
• Surgical washout
• IV antibiotics
• Differential: Gout
Septic Arthritis
Routes of infection
1.Haematogenous
2.Direct Trauma
3.Iatrogenic
4.Osteomyelitis
5.Inflamed extraarticular
structures
2 Minutes
5 Causes of Breast pain
Breast Pain? Back to the
Drinking…
I
G
E
T
V
I
N
O
Infectious / inflammatory Costochonditis
Genetic / ideopathic
Endocrine
Trauma
Vascular
Cardiac Pain
Iatrogenic / ingested
Neoplastic
Benigng or malignant breast cancer
Organs / other
Oesophagus: spasm; Heart :cardiac pain
Lung: pleurisy
Non-cancer conditions
Abnormalities of
development
• Cyclical mastalgia
• Non-cyclical
mastalgia
• Epithelial Hyperplasia
• Sclerosis
• Cysts
• Fibroadenoma
• Duct ectasia
Benign tumours
• Ductal papilloma
• Lipoma
• Oil cysts
• Sebaceous cysts
• Lymph nodes
• TB
Cancers
Non-invasive
• Lobular carcinoma in
situ
• Ductal carcinoma in
situ
Invasive
• 80% carcinomas are
ductal
– 5% lobular – poorer
outcome
Management
• Social / psych support
• Surgery
– Local / mastectomy
– reconstruction
• Radiotherapy
– Breast / axilla
• Chemotherapy
Modifying Oestrogen
• Oestrogen
• Progesterone
• Therapy aims to
reduce oestrogen
production
• Normal breast tissue
• AND 60% of tumours
• Ovarian ablation
• Pre-menopause prod.
– Ovaries
• Post Menopause
– Peripheral fats
– GNRH agonists
– Surigal or radiation
• Aromatase Inhibitors
– Post menopausal
Risk
Risk factors
• Menarche <11
• Menopause >54
• Western diet
• OCP and HRT
• Radiation
• Family history (only
5% of Br. Ca are
familial)
Inherited breast cancers
• BRCA1
– 51% by age 50
– 85% by age 70
– Also ovarian cancer
• BRCA2
– Male breast cancer
– Prostatic cancer
– Ovarian cancer
• Present early with
advanced disease
Risk Assessment
Think Benign
• Young patient
• No family history
• Smooth lump
• Movable lump
• Cyclical symptoms
Think Malignant
• Patient >55
• Family history br. Ca.
• Fixed mass
Testing for breast cancer
Triple Assessment
• Physical examination
• Imaging
– Ultrasonography (<35)
– Mammography
• Sampling
– USS guided core
biopsy
– Or FNA + cytology
– Ideally after imaging
The screening
programme
• Women
• Aged 50+
• Every 3 years
• 2 view mammography
• Will save ~1,250 lives
annually by 2010
• 1 / 500 screened
Describe some of the features
that make a disease suitable
for screening
A good screening Programme
• An important public health problem
• In which early detection is possible and
advantageous
• With a reliable, acceptable test
• And available, effective treatment
• There should be agreement on who is
suitable to investigate and treat.
Neoplasia
• 'Irreversible changes
in genetic material of
cells, due to exposure
to certain noxious
stimuli, leading to
abnormal cellular
growth patterns.’
• Tumours develop
from a single cell –
they are monoclonal
• Normal tissue is
polyclonal
• Learn
– Breast
– Bowel
– Lung
Neoplasia
• Oncogenes
– Abnormal expression
– Genes controlling cell
growth
– Dominant
• Tumor suppressor
genes
– Loss of activity
– Protect against
neoplasia
– Recessive
Neoplasia
• Tumor suppressor
genes
– Loss of activity
– Protect against
neoplasia
– Recessive
• p53, Chromosome
17
– initiates DNA repair
– prevents division of
cells with irreparable
DNA damage
• Rb, Chromosome 13.
– Abnormal copies of
this gene are
implicated in
retinoblastoma.
Growth Characteristics
Benign
Expands only
Grows locally
Generally slower
Malignant
Expands and invades local
tissues
May metastasise
Generally faster
Cytoplasmic Characteristics
Benign
Normal or slight increase in
nucleus:cytoplasm ratio
Resembles cell of origin (well
differentiated)
Retains specialisations
Diploid
Malignant
High nucleus:cytoplasm ratio
Failure of differentiation
Loses specialisations
Range of ploidy
Histological Characteristics
Benign
Few Mitoses
Cell uniform throughout
tumour
Organised tissue
Malignant
Many mitoses – some of which
are abnormal
Cells vary in shape and size
(cellular pleomorphism) and/or
Nuclei vary in shape and size
(nuclear pleomorphism)
Disorganised tissue
Invasion and Metastasis
• Invasion is the
spread into adjacent
tissues – may occur
along natural tissue
planes such as along
nerves
• Metastasis is the
spread of cells to
distant parts of the
body – there are
several mechanisms
for this
To Metastasise
• Changes occur in
only some cells of the
tumour
• By random mutation
• Binds to basement
membr
• Becomes motile
• Becomes able to attach
to extracellular matrix
• Becomes able to degrade
extracellular matrix
• Must be able to survive
and grow at site of
implantation
Routes of
Metastasis
• Vascular
• Lymphatic
• Coelomic
Local and systemic effects
Local
• Pressure
• Invasion
• Ulceration
• Obstruction
Systemic
• Weight loss
(cachexia)
• Loss of appetite
(anorexia)
• Fever
• Anaemia
• General Malaise
• Paraneoplastic
Who gets Cancers?
Inherited tendencies
• Xeroderma
pigmentosum
• Down’s syndrome
• Ataxia telangectasia
Genes
• Breast / ovarian
– BRCA1
– BRCA2
• Colon
– MLH1
Diseases predisposing
to cancer
• FPC: Colon
• HNPPC: Colon
• DNA mismatch repair
• Dominant
– MSH2
What is a carcinogen?
Suggest one together with its
mode of action.
Carcinogens
Cigarette smoke
UV Radiation
Chemicals
• PAH
• Aromatic amines
• Nitrosamines
Ionising radiation
• Radiotherapy
• Radon gas (lung)
• Industry/military
Carcinogens
Viruses
• EBV (Epstein-Barr)
• HPV (Papilloma virus)
• HBV (Hepatitis B
virus)
Stages in
carcinogenesis
• Initiation
• Promotion
• Progression