Overview Flashcards
EG. FLASHCARDS FOR NO LECTURE EDRF Effect of NO on smooth muscle Colour of nitrous acid Nitrous acid - formula Nitric oxide - formula Entonox - what is this and it's use? What is formed when NO is oxidised How does NO differ from nitrogen dioxide (it is a free radical)HAPE
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Define endothelium
Thin (single) layer of simple squamous epithelium
Composed of endothelial cells
Define EDRF
Endothelium derived relaxing factor aka. NO
Causes vascular smooth muscle to relax
Function of NO in blood vessels
Causes vascular smooth muscle to relax - vasodilation
Appearance of nitrous acid (HNO2)
This is colourless (this is NOT NO)
Nitrous oxide vs. nitric oxide - chemical formula
Nitrous oxide - N2O
Nitric oxide - NO
Define Entonox
Anaesthesia gas
Composed of 50% NO and 50% O2
Use of entonox
Pre-hospital care
Childbirth
Emergency medicine
Define free radical
Molecule with an unpaired electron in it’s outer valence/reactive shell
Free radicals - oxidising or reducing agents?
Free radicals look to take electrons - oxidising agents
Effect of NO being free radical?
NO is very unstable (but much more stable than other free radicals)
When is NO stable?
In body tissues where the PO2 is lower than 50mmHg
Reaction of NO with hydroxyl (OH) radical
NO + OH –> HNO2
Enzyme that synthesises NO?
Nitric oxide synthase (NOS)
Function of NOS
L-arginine + 1/2 O2 –> citrulline + NO (+ H+ + e-)
Three isoforms of NOS
1 - bNOS - brain
2 - iNOS - induced (not calcium dependent)
3 - eNOS - endothelial
Location of bNOS
Central and peripheral neuronal cells
Calcium dependent
Location of iNOS
Found in macrophages (also most nucleated cells)
Induced - not calcium dependent
Location of eNOS
Vascular endothelial cells
Calcium dependent
What can induce production of iNOS?
Inducible in the presence of inflammatory cytokines
How is NO synthesis regulated in the vascular endothelium?
Main regulation is via movement of blood past the endothelial wall - sheer stress opens calcium channels - calcium enters the endothelial cells - production of eNOS
Also via binding of ACh to the ACh recepors on the endothelium allows the entry of calcium
Pathway of eNOS activation in the vascular endothelium
Calcium - activates calmodulin
Calmodulin activates eNOS
Three cofactors required for synthesis of eNOS
Biopterin H4
FMN
FAD
Composition responsible for the production of activated eNOS from inactivated eNOS
Ca2+ + calmodulin
What does NO activate in smooth muscle cells?
Guanylate cyclase
What is the mechanism of action of guanylate cyclase?
Conversion of guanosine triphosphate in the smooth muscle to cyclic guanosine monophosphate (cGMP)
Effect of cGMP on the vascular smooth muscle?
cGMP - relaxation of vascular smooth muscle - vasodilation
Mechanism of action of NO causing smooth muscle relaxation
NO diffuses from endothelium to smooth muscle cells
NO activates guanylate cyclase
Guanylate cyclase converts guanosine triphosphate to cyclic guanosine monophosphate (cGMP)
cGMP causes smooth muscle relaxation
Effect of vasodilation?
Vasodilation increases local blood flow
This maintains low peripheral vascular resistance and a normal blood pressure
Effect of whole body inhibition of eNOS by drug?
This causes increased blood pressure esp. pulmonary arterial pressure
Two antagonisers of NO i.e. vasoconstrictors of the blood vessels?
Noradrenaline
Angiotensin
Damage to the NO system results in what complication?
Hypertension
Effect on blood flow to exercising muscles?
Blood flow increases over ten fold
Effect on blood flow to heart during exercise
Blood flow increases up to three fold
Effect on blood flow to kidney during exercise
Blood flow decreases by nearly half
Effect on blood flow to skin during exercise
Blood flow increases nearly four fold
Effect on blood flow to brain during exercise
Blood flow to the brain does not change
Receptors causing vasoconstriction of arterioles
Alpha-1 receptors
What causes the vasodilation to exercising muscles?
Chemical factors - NO and adenosine
Effect of sympathetic nervous system on arterioles
Vasoconstriction - NO and adenosine overcome this
How is NO production increased during exercise?
Increased local blood flow - increased sheering forces and opening of calcium channels - increased activation of eNOS - increased production of NO
How is NO produced in anaerobic metabolism?
Depletion of ATP produces lactate which lowers pH
Lowered pH produces nitrous acid HNO2 - can form NO
Two effects of exercise on the coronary arterioles and cause
Diameter of the coronary arterioles increases
Number of open arterioles (collaterals) increases
Caused by NO
Cause of angina during exercise
If atheromatous plaque is present - vessel cannot dilate - ischaemia and angina
Usage of NO for treatment of angina is given in the form of?
GTN - glycerin trinitrate
Two areas where NO has an effect?
Smooth muscle (around blood vessels) In the blood
Effect of NO in RBCs
NO reacts with oxyhaemoglobin to produce nitrosohaemoglobin
Effect of nitrosohaemoglobin
This displaces oxygen - increases delivery of oxygen to hypoxic tissue
Why does local hypoxia occur during exercise?
Occurs in muscles at the start of exercise
More ATP used than produced
Define persistent pulmonary hypertension of the newborn (PPHN)
Reduced pulmonary arterial resistance with the first breath does not occur - lungs are not properly perfused
Addition of NO to the inspired gas
Effect of low ventilation on NO levels and why?
Low ventilation causes low NO production because O2 is required for the production
SO low ventilation equates to low perfusion
Effect of exercise on the pulmonary circulation
Exercise causes increased CO - causes increased blood flow - the pulmonary arterial resistance decreases to maintain the BP
Receptors causing relaxation of bronchial smooth muscle
Beta 2 receptors
Effect of reduced NO in the brain
Reduced NO - reduces the cerebral blood flow
Resting blood flow through the brain
50ml/min/100gm
Blood loss causing reversible brain damage
Blood flow falls to half of normal - around 25
Blood loss causing irreversible brain damage
Blood flow falls to one quarter of normal - around 10-15
Function of basal release of NO
Prevention of leucocytes (anti-inflammatory) and platelets (anti-thrombotic) from adhering to the surface of the endothelium
Four functions of NO
Direct vasodilation
Anti-thrombotic effect
Anti-inflammatory effect
Anti-proliferative effect
How can iNOS lead to shock?
Overproduction of NO from macrophages can result in septic shock - uncontrollable vasodilation
Equation for blood pressure
BP = CO x SVR
Define cardiac output
Blood flow produced by the heart per minute
Define systolic BP
Maximum BP during ventricular contraction
Define diastolic BP
Minimum level of BP measured between the contractions of the heart
Eight components that can effect BP
Activity Temperature Diet Emotional state Posture Physical state Medication usage Ethnic background
Normal BP
120/80
Hypotension level
<90/60
Define postural hypotension
When the systolic decreases by 20 or the diastolic decreases by 10 when standing
Three causes of postural hypertension
Old age
Diabetes
Drugs
CNS effects of hypotension x4
Dizziness
Impaired cognition
Lethargy and fatigue
Visual disturbances (hypoperfusion of brain)
Muscle effects of hypotension x2
Paracervical backache (upper back) General fatigue
Boundary for hypertension
140/90 persistently
Range of prehypertensio
130-139/85-89
Range of prehypertensio
130-139/85-89
Are prehypertensives candidates for drug therapy?
No - lifestyle modification
Isolated systolic hypertension
Systolic: >140
Diastolic: <90
Three lifestyle modifications to reduced BP
Weight loss
Increased physical activity
Limited alcohol consumption
What should be avoided prior to blood pressure measurements (x3) and for how long?
Caffeine
Exercise
Smoking
At least 30 minutes
Which BP increases with age?
Systolic
Four adverse effects of hypertension
Stroke
Coronary heart disease
Renal impairment
Peripheral vascular disease
Each 20/10mmHg increase in BP increases the risk of mortality by what rate? What age group is this prevalent in?
Doubles the risk
40-69 years
What is HOTT?
Hypertension Optimal Treatment Trial
What is HOTT?
Hypertension Optimal Treatment Trial
Results of HOTT - what did it tell us?
Lowest incidence of CV events when DBP maintained at 83
and maintained at <80 in diabetics
SO especially important to control hypertension in diabetics
Concentric hypertrophy
Thickened wall of the left ventricle
Decreased lumen diameter
Must increase the HR to maintain CO
Eccentric hypertrophy
Whole ventricle enlarges - enlarged heart is weaker
Effect of chronic hypertension on the heart
Results in concentric hypertrophy
SO then the HR increases
Effect of chronic hypertension on the eyes x3
Chronic hypertension damages the retina
Cotton wool spots
Silver wiring
Severe cases: swelling of the optic disc i.e. papilledema
Define pailledema
This is swelling of the optic disc of the eye
Primary hypertension cause
Idiopathic - genetic
90-95% of cases
Secondary hypertension cause x5
5% of cases
Renal disease Endocrine disease Coarctation of the aorta Iagtrogenic i.e. hormonal/oral contraception, NSAIDs Thyroid - hyper or hypo
Two systems to control BP
Neuronal - baroreceptors
Hormonal - RAAS
Location of baroreceptros
Carotid artery - carotid sinus
Aortic arch
These are mechanoreceptors
Timescale of the RAAS system to maintain BP
Maintenance of steady, long term pressure
Timescale of the RAAS system to maintain BP
Maintenance of steady, long term pressure
RAAS pathway
Angiotensinogen to angiotensin I via renin
Angiotensin I to angiotensin II via ACE
Effects of angiotensin II x3
Increased sympathetic action
Release of aldosterone
Increased secretion of ADH
Increased levels of what may be present in patients with hypertension? x2
Increased renin
Increased angiotensin II
Effect of hypertension on salt and water and why?
Excess salt retention - raised water levels causes change in osmotic pressure
Retention of water - raised ADH
Two key treatments in hypertension (non-pharmacological)
Dietary salt restriction
Diuretics
Normal sodium levels
Between 135 and 145mmol/L
Hyponatremia
Sodium levels <135mmol/L
Three symptoms of mild hyponatraemia
Loss of energy and fatigue
Confusion
Muscle weakness
Six symptoms of severe hyponatraemia
Nausea and vomiting Headache Spasms Restlessness and irritability Seizures Coma
Prevalence of hypertension in type II diabetics at age 45
40%
Prevalence fo hypertension in type II diabetics age 75
60%
BMI for obesity
> 30
Five factors that are raised in obese patients that can result in the onset of hypertension
Increased renal renin release
Increased angiotensin formation
Increased sodium retention
High levels of leptin - increased sympathetic vasoconstriction
Hyperinsulaemia - insulin induced hyperkalaemia
First line treatment for hypertension
Lifestyle changes - exercise, increased fruit and veg and decreased salt, reduced weight if obese
First line pharmacological treatment for hypertension
Thiazide diuretic
Name of thiazide diuretic used in the treatment of hypertension
Bendroflumethazide
Second and third line treatment of hypertension
Thiazide + beta blocker or ACE inhibitor
Angiotensin receptor blocker
Fourth line treatment of hypertension
Calcium channel blocker
Final line treatment of hypertension
Alpha blocker
First line pharmacological treatment for hypertensive diabetics
ACE inhibitors or angiotensin receptor blockers
Most important first line treatment for obese hypertensives
Exercise and try to lose weight
Therapeutic target for hypertensives
<140/85 in clinic
<130/80 at home
Therapeutic target for diabetic hypertensives
<140/80 in clinic
<130/75 at home
Define erythropoesis
Production of red blood cells
Sites of erythropoesis prior to brith
1-3 week - yolk sac and mesothelial layers of the placenta
6 week - liver and spleen
3 month - bone marrow as the bones form
0-5 years - site of erythropoiesis
Bone marrow of all bones
5-20/25 years site of erythropoiesis
Bone marrow of the long bones
25 years + site of erythropoesis
Bone marrow of membranous bones - vertebrae, sternum, ribs, cranial bones, ileum
Name the 5 membranous bones
Verterbae Sternum Cranium Ribs Ileum
Define myeloid tissue
Bone marrow
Red bone marrow function
Site of erythropoiesis
Yellow bone marrow function
Contains large amounts of fat droplets and cells
Stages of production of an erythrocyte
Haematopoetic stem cell Common myeloid progenitor cell (committed at this stage) Proerythroblast Early erythroblast Late erythroblast Erythroblast Normoblast Reticulocyte Erythrocyte
Cytoplasm of what cell stains blue?
Proerythroblast
How to recognise proerythroblast?
Bright blue rim of cytoplasm around blue nucleus
How to recognise early erythroblast?
Polychromatic i.e. many coloured nucleus
Cells that contain ribosomal RNA in them are?
Reticulocytes
Define diapedesis
Passing of the erythrocytes through pores in the capillary membranes from the bone marrow into the blood
Diameter of erythrocytes
7.8um
Volume of erythrocyte
90cu mm
Volume of RBC in microcytic anaemia
<79/80fl
Volume of RBC in macrocytic anaemia
> 100fl
Normal RBC count - general
Around 5 million per microlitre
Normal lifespan of RBC
120 days (+/- 30 days)
RBC count in men
5.2 x0.3x10^6
RBC count in women
4.7 x0.3x10^6
Component that controls erythropoiesis is?
EPO - erythropoietin
Production site of EPO
Fibroblasts in the kidney - at the proximal convoluted tubule
Glomus cells of the carotid body
Why is EPO only produced in these specific locations?
Oxygen levels here are not affected by exercises or BP changes - steady usage of oxygen
What are EPO secreting cells sensitive to?
Hypoxia
Hypoxia stimulates increased EPO release
Anaemia caused by kidney damage and why?
Kidney damage - reduced EPO production
This can cause microcytic anaemia
Charge on erythrocytes
Outside negative surface charge due to presence of glycoproteins - causes them to repel and not stick to each other
Define rouleaux
Clumping of erythrocytes caused by reduced charge on their surface
Cause of rouleaux x2
Inflammatory reactions Bacteria in the blood
Define ESR
Erythrocyte sedimentary rate
Significance of raised ERS
Non-specific marker for infection in the blood (due to formation of rouleaux)
Two reasons RBCs need ATP
Sodium pumps in the membrane
GLUT1 transporters to consume glucose
Metabolism of RBCs
Anaerobic glycolysis (and pentose phosphate pathway)
Name the four myeloid cells
M M Me Megacaryocyte Mast Cell Myeoblast Erythrocyte
Cells and site of removal of RBCs from the body
Removed via macrophages when passing through the spleen
Three signals indicating need for removal of RBCs
Cell surface antigens of old cells differ to that of young cells
Increased levels of methaemoglobin
RBCs become more rigid and trapped in splenic capillaries
Breakdown of haem via what enzymes
Haem to biliverdin via haemoxygenase
Biliverdin to bilirubin via biliverdin reductase
Colour of biliverdin
Green
Globin proteins are broken down into what?
Amino acids
Unconjugated bilirubin
When bilirubin is bound to albumin in the splenic macrophages and released into the blood
Conjugated bilirubin
Occurs in the liver
Bilirubin attaches to glucoronic acid via hepatocytes and is now more soluble
How is conjugated bilirubin excreted?
Converted to urobilnogen in the small intestine - passes out in faeces (10% in urine)
Site of haemoglobin to biliverdin
Spleen
Site of biliverdin to bilirubin
Liver
Site of bilirubin to urobilnogen
Small intestine
Acid that binds to bilirubin to form conjugated bilirubin
Glucoronic acid
Stercobilin
10% of urobilnogen converted to this - excreted in the urine
Define arteriosclerosis
Thickening of an arterial wall which then loses elasticity
Sclerosis - hardening
Most common form of ateriosclerosis
Athersclerosis
Three stages of atherosclerosis
Endothelial damage (and activation)
Uptake of modified LDLs, adhesion and infiltration of macrophages
Smooth muscle proliferation and formation of fibrous cap
Four functions of the endothelium
Vasomotor tone
Thrombosis - antithrombotic properties
Production of inflammatory factors
Production of cellular adhesion molecules (CAMs) - receptors for monocytes
Four causes of endothelial damage
Shear stress e.g. turbulent blood flow
Toxic damage e.g. free radicals
High levels of lipids
Viral or bacterial infection
Function of lipoproteins
Transportation of fat in the blood
Five types of lipoproteins
Chylomicrons VLDL LDL IDL HDL
LDL vs. HDL
LDL - bad - composed of mainly cholesterol
HDL - good - composed of mainly protein
Two ways in which LDLs can become modified
Oxidation
Glycation
Glycation of LDLs is prevalent in?
Diabetes mellitus - high glucose levels
Effect of oxidised LDL?
This can act to cause endothelial damage itself
Infiltration of macrophages occurs as?
Increased monocytes bind to CAM - crosses endothelium and transformed into macrophages
Define foam cells
Lipid laden macrophages
How are foam cells formed?
Macrophages pick up excess levels of modified LDL via scavenger receptor and grow larger and larger
LDL apolipoprotein B100
Apoliprotein B100 present on?
VLDL
IDL
LDL
Apoliprotein present on chylomicrons?
B48
Fatty streak of atheroma occurs in which layer of the artery?
Occurs in the tunica intima
Component causing smooth muscle proliferation in arteriosclerosis?
Platelet derived growth factor (PDGF)
Two cell types that release PDGF?
Endothelial cells
Macrophages
What are the two types of smooth muscle?
Resting - contractile
Proliferating - secretion of extracellular materials
What is broken down by the proliferating smooth muscles?
Internal elastic lamina
How is a thrombus formed by the smooth muscle cells?
Proliferating smooth muscle cells
Secretion of extracellular materials e.g. collagen
Collagen - platelets will stick to this and form a thrombus
Four common sites of atheroma formation
Carotid bifurcation
Aortic bifurcation
Lateral walls of the common iliac arteries
Coronary arteries
Unmodifiable risk factors for atheroma formation x3
Age
Sex
Family history
Modifiable risk factors for atheroma formation x5
Dyslipidaemia Smoking Hypertension DM Physical activity
Define dyslipidaemia
Elevated LDL/cholesterol levels
Desirable total cholesterol levels in adults
<200mg/dl
Desirable LDL and HDL levels in adults
LDL - <130
HDL - <40
Three emerging risk factors for the onset of atherosclerosis
Homocysteinaemia
Lipoprotein a
Infection
Three treatment options for atheroma formation
Modifiable risk factors
Plasma lipid reduction - statins
Polypill usage
What is contained in the polypill? x5
Statin
Three BP lowering drugs - thiazide, beta blocker, ACE inhibitor
Folic acid
Aspirin
Complications from atheroma formation x5
Coronary artery disease - MI/angina Peripheral vascular disease Stroke Aneurysm Renal artery stenosis
Surgical interventions for atherosclerosis x3
CABG
PCI
Stent
Arterial stent generally done in which artery?
Generally done via radial artery rather than the femoral artery
Two types of angina and causes
Stable - coronary artery disease
Unstable - acute myocardial infarction
Typical history of stable angina (from the patient)
Central chest pain comes on following exertion
Stops when exertion is ceased
Two main causes of angina
Decreased myocardial oxygen supply
Increased myocardial oxygen demand
Two causes of reduced myocardial oxygen supply
Coronary heart disease
Severe anaemia
Three causes of increased myocardial oxygen demand
Left ventricular hypertrophy
Right ventricular hypertrophy
Rapid tachyarrythrmias
Five indications for cardiac referral of a patient
New onset angina
Exclusion of angina in high risk individuals with atypical symptoms
Worsening angina in patient with previously stable symptoms
New or recurrent angina in patient with history of e.g. MI
Assessment of occupational fitness eg. airline pilots
Four methods for diagnosis of angina
Clinical assesment
Electropcardiography
LV wall motion analysis
Perfusion imaging
Diagnostic features for assessment of angina x6
HISTORY Character - tight Location - chest central Radiation - arms, throat, jaw Duration - 5-10 minutes at the most Provocation - exertion
ECG results of patient stable angina - resting vs. exercise ECG
Resting ECG - can be normal
Exercise ECG - abnormal
Exercise ECG - stable angina appearance
Planar or down-sloping ST depression
ST depression is indicative of what?
ST depression - indicates ischaemia
Main non-invasive investigation for angina
Exercise ECG
Functional imaging investigations for angina x3
Isotope perfusion imaging
MR perfusion imaging
Dobutamine stress echo
Drugs to increase O2 delivery for angina x4
Nitrates
Calcium channel blockers
Nicorandil
Revasc
Drugs to reduced oxygen demand in angina
Beta blockers Nitrates Nicorandil Calcium channel blockers Trimetazidine Ivabridine
Secondary prevention of angina
Aspirin and statins primarily
Also ACE inhibitors
Surgical interventions for the management of angina
CABG
PCI
Diagnostic criteria for MI
Change in the troponin levels (increase) PLUS at least one of:
Symptoms of ischaemia
New ST segment/T wave changes
Pathological Q waves
Imaging evidence of lack of wall motility
Presence of thrombus on angiograph
Increased troponin levels indicate?
MI - cardiac muscle damage
Where is troponin found?
Found only in cardiac myocytes
Change on ECG required for MI?
Not for NSTEMI
YES for STEMI - ECG is diagnostic for STEMI
Two types of MI
NSTEMI - non-ST elevation myocardial infarction
STEMI - ST elevation myocardial infarction
STEMI vs. NSTEMI
STEMI - ruptured coronary plaque and occlusive thrombus
NSTEMI - ruptured coronary plaque and subocclusive thrombus
Type 1 AMI and cause
Spontaneous AMI
Plaque rupturing
Five cardiac signs of AMI
Chest pain 4th heart sound Low grade fever Leucocytosis and raised inflammatory markers Troponin leak (increased levels)
Three autonomic symptoms of AMI
Tachycardia
Sweating
Vomiting
Five traits that may result in a delay for calling for help when experiencing an AMI
Older people Women Nocturnal or weekend pain No previous AMI People with diabetes
What percentage of people who die from an AMI do so before reaching the hospital?
33%
What is the mortality rate after one year of an AMI?
40%
Major cause of morbidity in AMI patients?
Cardiogenic shock - left ventricular failure
Treatment for STEMI
Reduction of the size of the infarct via thrombolytic drugs
and reperfusion therapy
Two main types of thrombolytic drugs
Streptokinase
Tissue plasminogen activator (tPA)
What are thrombolytic drugs?
These work to dissolve the blood clots
Action of streptokinase
Lysis of fibrin in the thrombus
Action of tPA
Converts plasminogen to plasmin –> this lysis the fibrin in the thrombus
Main method for reperfusion therapy?
Primary PCI
What should be provided prior to primary PCI?
Anti-platelet drugs i.e. aspirin/heparin
Prevention treatment for AMI following discharge?
Lifestyle - smoking, diet, exercise
Prevention durgs - aspirin, statin, beta blocker, ACE-inhibitor , tricagrelor
Prevention devices e.g. ICD
Should tricagrelor be given for life treatment?
No
How many patients with AMI are smokers?
20%
How many patients with AMI under 60 years are smokers?
50%
What percentage of AMI sufferers quit smoking?
33%
Volume of RBCs in the body
24x10^12
RBC lifespan
120 days - about 4 months
RBCs make up what proportion of all body cells?
1/3
RBC approximate death rate
2x10^11
Average diet contains how much iron per day?
15mg
What is the total quantity of body iron?
3-5mg
Most iron in the body is in what form?
Circulating haemoglobin - 2mg
Where is the majority of iron absorbed in the body?
Duodenum
Cells that absorb iron are? Location?
Enterocytes in the duodenal lining
Two forms in which iron can be absorbed
Free iron in the ferrous form Fe2+
Protein e.g. haem
Ferrous iron formula
Fe2+
Ferric iron formula
Fe3+
Function of ferric reductase on iron
Ferric reductase reduces Fe3+ to Fe2+ (for absorption)
What component regulates the level of free iron in the plasma?
Transferrins
What component transports iron from the bone marrow into the blood?
Transferrins
How many iron atoms can transferrins hold and in what form?
Can hold two iron atoms in the ferric (Fe3+) form
Location of transferring receptor
Erythroblast
Release of iron from transferring occurs where?
Within the cell i.e. erythroblast via endocytosis
Free iron in the erythroblast is taken up by?
Ferritin
How is iron stored in cells?
Bound to ferritin
How is iron released from ferritin?
Controlled fashion - when needed
Common diagnostic test for iron deficiency anaemia
Serum ferritin levels - indirect marker of stored iron
Define anaemia
Low hb. level <13.5g/dl male and <11.5g/dl female
Most common blood disorder of patients
Anaemia
Anaemia hb. level in child 6 months to 6 years
<11g/dl
Anaemia hb. level in child 6 years to 14 years
<12 g/dl
Three variables that alter normal hb. level
Age (decreases with age)
Sex
Racial background
Five further tests if hb. is low
History and examination Full blood count and blood film Serum 12, folate, ferritin Renal and liver function tests ESR
Symptoms of anaemia x5
Tiredness Fainting Shortness of breath Worsening angina/claudication Palpitations
Signs of anaemia x6
Pallor Rapid heart rate Bounding pulse Systolic flow murmur Cardiac failure Retinal haemorrhages
Causes of reduced production of RBCs leading to anaemia x6
Iron deficiency B12/folate deficiency Marrow infiltration e.g. cancer Chronic disease Infections e.g. HIV/parvovirus
Causes of increased destruction of RBCs leading to anaemia x1
Haemolytic anaemia
Causes of increased loss of RBCs leading to anaemia x1
Bleeding
Two most common causes of anaemia
Iron deficiency and B12/folate deficiency
MCV of microcytic anaemia
<76fl
MCV of macrocytic anaemia
> 96fl
Volume of normocytic anaemia
76-96fl
Two main microcytic anaemias
Iron deficiency anaemia
Thalassaemia
1ml of blood contains how many mg of iron?
0.5mg
Major source of haem iron is?
Food of animal origin
Factors that can enhance iron absorption x6
Haem iron - meat Ferrous salts - Fe2+ Acidic pH Iron deficiency Pregnancy Hypoxia
Factors that can impair iron absorption x5
Non-haem iron i.e. veg Ferric salts - Fe3+ Alkaline pH Iron overload Inflammatory disorders
Common drug that can decrease iron absorption
Protein pump inhibitors for acid reflux/indigestion
Causes of iron deficiency anaemia x10
Menorrhagia Varices Ulcer Inflammatory bowel cancer Coeliac Atrophic gastritis Growth spurts Pregnancy Elderly Vegans Hookworm
Histological cell which signifies iron deficiency anaemia is?
Pencil cell
Tablets given to treat iron deficiency anaemia?
Ferrous sulphate
Four causes of normocytic anaemia
Acute blood loss
Chronic disease
Cancer
Haemolysis
Three causes of macrocytic anaemia
B12/folate deficiency
Alochol/liver disease
Myelodysplasia
Specific function of B12/folate
Conversion of homocysteine to methionine (DNA synthesis)
B12 and folate deficiency result in what type of anaemia?
Macrocytic - cells fail to divide
B12/folate - which is destroyed by cooking?
Folate
How long is B12 stored for in the body?
Three years
How long is Folate stored for in the body?
Four months
Where is B12 absorbed?
Ileum - bound to IF
Where is folate absorbed?
Duodenum and jejunum
What is B12 bound to in the body?
Intrinsic factor
Cells that produce IF are?
Parietal cells of gastric mucosa
Lack of IF results in?
Pernicious anaemia
Histological appearance of B12/folate deficiency?
Hypersegmented neutrophils
Two main causes of B12 deficiency
Nutritional - lack in diet
Malabsorption - gastric i.e. IF or intestinal e.g. chron’s disease
Pernicious anaemia?
Lack of IF
Autoimmune disorder - action of autoantibody
Autoantibody in pernicious anaemia attacks what? x2
Gastric mucosa
IF
Five signs of pernicious anaemia
Insidious - gradual onset Anaemia Glossitis Mild jaundice Neurological symptoms
Treatment for pernicious anaemia
Intramuscular B12 once every three months for life
Four signs of folate deficiency
Insidious
Anaemia
Glossitis
Mild jaundice
NO neurological signs!
Treatment for folate deficiency
Oral folic acid
Define haemolytic anaemia
Lifespan of RBC <120 days
Three signs of haemolytic anaemia
Jaundice
Increased LDH levels
Spherocytosis
Three signs of haemolytic anaemia - explain
Jaundice - increased release of bilirubin (can lead to gallstones)
Increased levels of LDH - released from the cells
Spherocyte formation
Four haemolytic anaemias
Hereditary spherocytosis
Sickle cell disease
Thalassaemia
Glucose-6-phosphate dehydrogenase deficiency
Signs of haemolytic anaemia x4
Pallor and anaemia
Jaundice
Gallstones
Splenomegaly
Inheritance pattern of hereditary spherocytosis
Autosomal dominant
G6PD function
Prevents/reverses the oxidation of Hb. membrane SO prolongs the lifespan of RBC
Inheritance of G6PD deficiency
X-linked
Immunoglobulin involved in autoimmune haemolytic anaemia
IgG
Investigation for autoimmune haemolytic anaemia
Direct Coombs test/Direct antiglobulin test
Define stroke
Interruption of cerebral blood flow causing ischaemia and hypoxia
Two causes of stroke
Infarction - blockage of artery
Haemorrhage - rupture of aneurysm
Two divisions of haemorrhagic stroke
Parenchymal - into the brain tissue
Subarachnoid - into the subarachnoid space
Stroke is the ____ most common cause of death in the UK? After what?
Third most common
Heart disease
Cancer
Direct Coombs test/direct antiglobulin test is used for?
Investigation of autoimmune haemolytic anaemia
Stroke symptoms are quick or gradual?
QUICK
Symptoms of stroke
Sudden numbness/weakness of face/limbs
Sudden confusion
Sudden trouble with vision
Sudden severe headache
FAST pneumonic for symptoms
Face
Arms
Speech
Time
Stroke golden hour
Interventions in the first hour following stroke make significant difference to outcome
Four types of stroke
TIA
Thrombotic - ischaemic
Embolic - ischaemic
Haemorragic
Maximum length of a TIA
24 hours - clinically this is only for 85% of patients
Typical length of a TIA
<1 hour
Cause of TIA
Release of small emboli from a thrombus
Temporary downstream blockage of vessel
What is thrombotic stroke?
Development of atheroma in a cerebral vessel - ruptures and forms local clot
What is embolic stroke?
Embolism occurs from an original thrombus
Original thrombus in this case is not in cerebral arteries
Main feature of embolic stroke?
Rapid development of neurological signs
Thrombotic and embolic strokes make up what percentage of all strokes?
85%
Source of embolism in embolic stroke is usually where?
Left side of heart
Key feature of haemorrhagic stroke is? x2
Severe headache
Stupor/coma that may progress with time
Cause of haemorrhagic stroke
Rupture of blood vessel
Define lacunar stroke
Occlusion of artery supplying deep structures rather than cortex
Basal ganglia, thalamus, pons, cerebellum
Presence of cortical infarct signs in lacunar stroke?
Absent
Three forms of lacunar stroke?
Motor hemiparesis with dysarthria
Ataxia and hemiparesis
Dysarthria and clumsy hand
Define dysarthria
Difficult or unclear articulation of speech due to poor articulation of the muscles of speech
Define ataxia
Loss of full control of bodily movements
Main feature of embolic stroke?
Rapid development of neurological signs
Thrombotic and embolic strokes make up what percentage of all strokes?
85%
Source of embolism in embolic stroke is usually where?
Left side of heart
Key feature of haemorrhagic stroke is? x2
Severe headache
Stupor/coma that may progress with time
Cause of haemorrhagic stroke
Rupture of blood vessel
Define lacunar stroke
Occlusion of artery supplying deep structures rather than cortex
Basal ganglia, thalamus, pons, cerebellum
Presence of cortical infarct signs in lacunar stroke?
Absent
Three forms of lacunar stroke?
Motor hemiparesis with dysarthria
Ataxia and hemiparesis
Dysarthria and clumsy hand
Define dysarthria
Difficult or unclear articulation of speech
Define ataxia
Loss of full control of bodily movments
Motor hemiparesis with dysarthria where is the lesion?
Infarct in the posterior limb of the internal capsule
Ataxia and hemiparesis where is the lesion?
Infarct in the posterior limb of the internal capsule
Dysarthria and clumsy hand where is the lesion?
Infarct in the anterior limb of the internal capsule
Impaired function of cerebral sodium pump results in? x2
Swelling of the brain nerve cells (increased leakage of Na+ and hence water into the cell)
This swelling results in increased ICP
Why do cerebral nerve cells require a very high level of sodium pumps?
Have a very large surfaced-area to volume ration - increased sodium leakage
Hypertension accounts for what percentage of stroke risk?
35-50%
Those with AF have what percentage risk of stroke per year?
5%
Name five lesser risk factors for stroke
Hypercholestrolaemia Migraine Obstructive sleep apnoea Diet low in potassium Thiazide and loop diuretics
Most common artery for stroke
Middle cerebral artery
Why is MCA prone to aneurysms and stroke?
Highly tortuous artery
Lenticulostriate arteries - supply and origin
Arteries to the basal ganglia and the internal capsule
Leave MCA at 90 degree angle
Function of internal capsule
Motor commands from motor cortex to brainstem and sinal cord
Function of cerebral sodium pump x2
Maintains the membrane potential
Maintains the nerve cell size and shape
Impaired function of cerebral sodium pump results in? x2
Swelling of the brain nerve cells (lack of movement of Na+ and water out of the cell)
This swelling results in increased ICP
Why do brain cells have the highest consumption of ATP?
Most of the ATP is required to fuel the sodium pump
Three main treatment strategies for stroke
Restore blood flow
Combat excitotoxicity
Combat free radical damage
How can blood flow be restored following stroke?
Introduce tissue plasminogen activators - to burst the clots
Which cells remove potassium from the extracellular space of the brain?
Glial cells - take up the potassium
Hypoxic brain - effect on potassium levels?
In a hypoxic brain, the glial cells do not take up the potassium - increased extracellular potassium levels
Superoxide dismutase
Free radical scavenging enzymes against ROS
Cause of exocitotoxicity in hypoxic brain
Excess release of nuerotransmitters
Two main glutamate receptors
AMPA
NDMA
Consequence of excitotoxicity in the brain
Increased influx of calcium in the cell - this increases the metabolic demand - formation of free radicals
Define penumbra
Middle region around a stroke focus - the neurones are damaged by they can survive if intervention occurs
Three main treatment strategies for stroke
Restore blood flow
Combat excitotoxicity
Combat free radical damage
Three drugs to combat the excitotoxicity
NMDA antagonists
AMP antagonist e.g. NBQX
Lithium
Three methods to reduce free radial damage of the brain
Antioxidants e.g. vitamin C and E
Enzymes - superoxide dismutase
Cool down the brain
Superoxide dismutase
Free radical scavenging enzymes against ROS
Define clinical shock
Acute circulatory failure with inadequate or inappropriately distributed tissue perfusion resulting in cellular hypoxia
Two components of shock syndrome
Hypotension
End organ injury
Normal CO
5l/min
Normal MAP
100mmHg
MAP of shock
MAP <60mmHg
Equation for BP
COxSVR
Equation for CO
CO = HR x SV
Two hormones that act to maintain SVR and their receptors
Noradrenaline - alpha-1 receptors
Angiotensin 2 - angiotensin AT1 receptor
These are vasoconstrictors
What is the most common cause of low CO
Generally due to low SV
HR tends to be compensation
Starling’s law of the heart
The force of contraction increases as the end diastolic volume increases
SO the greater the preload, the greater the force of contraction so the greater the stroke volume
Location of alpha-1 receptors and angiotensin receptors
Alpha adrenoreceptor - on the outside
Angiotensin receptor - lumen
Three factors that can increase myocardial contractility
Sympathetic NS
Catecholamines i.e. adrenaline/noradrenaline
Ionotrope drugs
Receptor for ionotropoic drugs
Beta-1 receptor
Four factors leading to reduced myocardial contractility
Cardiac disease
Hypoxia/hypercapnia
pH/electrolyte disturbance
Drugs e.g. BBs or CCBs
How is SVR maintained?
Constriction of arterioles in end organs
Two hormones that act to maintain SVR and their receptors
Noradrenaline - alpha-1 receptors
Angiotensin 2 - angiotensin receptor
These are vasoconstrictors
Two local vasodilators
No
Prostacyclin
Local vasoconstrictor
Endothelin
Cells that produce prostacyclin
Endothelial cells
Prostacyclin is produced from what?
Arachidonic acid
Two functions of prostacyclin
Inhibits platelet activation
Local vasodilator - reduces calcium entry into smooth muscle
Hormone that antagonises the effects of prostacyclin is?
Thromboxane
Compensated shock
Initial stage of shock
Decompensated shock
Later stage of shock - organs cannot be perfused and start to fail
Four main classes of shock
Obstructive shock
Distributive shock
Hypovolaemic shock
Cardiogenic shock
Obstructive shock and example
Physical obstruction causing failure of cardiac output e.g. pulmonary embolism
Main sign of septic shock
Fever
Hypovolaemic shock and eg
where you have bled and lost too much blood so there is not enough circulating blood so that even if you were to increase the heart rate, preload cannot increase e.g. haemorrhage
Cardiogenic shock and eg
Failure of the heart to pump efficiently and supply blood to the body e.g. myocardial infarction/heart failure
Classic presentation of hypovolaemic shock
Low BP High HR Confusion Anxiety Greyish pallor Oligouria
Effect of breath sounds on obstructive shock
Breath sounds are absent on the affected hemiothorax
Volume of blood loss that is life threatening
> 40% - >2litres
At whcih stage of hypovolaemic shock will treatment be required
Stage 3 - prior to this can be compensated for
Immediate compensation to shock
Increased sympathetic - HR and contractility via baroreceptors
Release of ADH vasopressin
Longterm compensation to shock
Renin, aldosterone release, increased thirst sensation, increased EPO production
Name of cells that produce EPO
Peritubular fibroblasts
Four stages of hypovolaemic shock
1 - <15% loss of blood
2 - <30% loss of blood
3 - >30% loss of blood
4 - >40% loss of blood
Septic shock is a form of which type of shock?
Distributive
Composition of feotal hb
Two alpha
Two gamma
Composition of adult Hb. (HbA)
Two alpha and two beta
Genes for alpha subunit - chromosome?
Alpha subunit - 2 genes on chromosome 16
Genes for beta subunit - chromosome?
Beta subunit - 5 genes on chromosome 11
Five genes for beta subunit
Gamma A Gamma G Epsilon Delta Beta
HbF compared to HbA
HbF can bind O2 more efficiently than HbA
Hb. Gower-1 and composition
Very first form of Hb - first six weeks
Two zeta
Two epsilon
Composition of HbA2
Two alpha
Two delta
Beta thalassaemia cause
Mutation on chromosome 11
Alpha thalassaemia
Deleted/faulty genes on chromosome 16
Beta thalassaemia
Deleted/faulty genes on chromosome 11
Four forms of alpha thalassaemia and cause
Minima - one gene defective - silent carrier
Minor - two genes defective
Hb H disease - three genes defective
Hydrops fetalis - four genes defective - incompatible with life
Hydrops fetalis stillborn infant cause
Four defective genes on chromoome 16
Beta thalassaemia cause
Point mutation on chromosome 11
MCV of haemolyic anaemia
6-8g/dL
Two forms of beta thalassaemia
Heterozygous - minor
Homozygous - major
Consequence of beta thalassaemia major
Cannot produce sufficient levels of HbA either
HbE
Hb with single point mutation in Beta chain
Mitral valve prolapse
> 2mm systolic prolapse of one or both valve leaflets into the LA
Cause of SCA
Mutant form of beta subunit
Mutation of glutamic acid to valine (GAG to GTG) at codon 6 of chromosome 11
HbC
Hb with abnormal beta subynit
HbE
Hb with single point mutation in Beta chain
Most common valve lesion
Mitral valve prolapse
Symptoms of mitral valve prolapse
Asymptomatic
Signs of mitral valve prolapse
Ejection click and late systolic murmur
Treatment of mitral valve prolapse
Usually none necessary
Symptoms of aortic stenosis x5
Dyspnoea Angina Syncope LVF Sudden death
Three causes of aortic stenosis
Calcific disease
Congenital bicuspid valve
Rheumatic disease
Cause of rheumatic disease
Group A haemolytic strep infection
Aortic stenosis indications for surgery
Any symptoms of AS
Echocardiographic evidence of worsening LV dilatation
Peak systolic pressure gradient >50mmHg
Causes of aortic regurgitation
Calcification Congenital bicuspid valve Rheumatic disease Infective endocarditis Ankolysing spondylitis Marfan syndrome Aortic dissection
SAME AS AORTIC STENOSIS + INFECTIVE ENDOCARDITIS
Symptoms of aortic regurgitation x2
NB. Often none
Dyspnoea - contractile failure
Angina - increased O2 demand of LV
Causes of aortic regugitation
Calcification Congenital bicuspid valve Rheumatic disease Infective endocarditis Ankolysing spondylitis Marfan syndrome Aortic dissection
Symptoms of aortic regurgitation
a
Signs of aortic regurgitation
Rapidly rising carotid pulse (increased preload)
Early diastolic murmur
Ejection murmur
Rising carotid pulse aortic stenosis vs. aortic regurgitation
Aortic stenosis - slow rising
Aortic regurgitation - rapid rising
Effect of aortic regurgitation on the LV
Dilatation due to increased volume/volume overload
Investigation for aortic regurgitation
Echo-doppler
Aortic regurgitation - indications for surgery
Any symptoms of AR
Echocardiographic evidence of worsening LV dilatation
Cause of mitral stenosis
Rheumatic fever
Signs of mitral stenosis x3
Fast pulse
Mid-diastolic rumble
Increased JVP, Basal crepitations, Ankle oedema - due to volume overload
Define orthopnoea
Shortness of breath i.e. dyspnoea when lying flat
Signs of mitral stenosis x3
Fast pulse
Mid-diastolic rumble
Increased JVP, Basal crepitations, Ankle oedmea - due to volume overload
Investigation for mitral stensos
Echocardiogram + doppler
Treatment for mitral stenosis x2
Valvuplasty - replacement of valve
Angioplasty - dilate the valve
Mitral valve disease - indications for surgery
Symptoms that fail to respond to medical treatment
Worsening cardiovascular complications
Symptoms and signs of mitral regurgitation
Same as mitral stenosis
Mitral valve disease - indications for surgery
Symptoms that fail to respond to medical treatment
Worsening cardiovascular complications
Location of cardiac plexus
Anterior to the carina - bifurcation of trachea at L4/L5 and posterior to arch of aorta
Cardioinhibitory centre
Parasympathetic to the heart - reduces the heart rate
Synapse with the vagus
To the SAN and the AVN
Sympathetic innervation to the heart from?
Sympathetic trunk
Visceral general afferents
Cardioinhibitory centre
Parasympethetic to the heart
Synapse with teh vagus
Cardioinhibitory centre location
The medulla
Three nuclei of the vagus nerve
Dorsal motor nucleus
Nucleus ambiguus
Solitary nucleus
Cardioacceleratory centre function x2
Sympathetic innervation:
Increase HR
Increase force of contraction
Location of cardioacceleratory centre
Medullar - reticular formation
Autonomic region of grey matter in the spinal cord?
T1-T4
Lateral horn
Anterior chamber of the heart is?
Right ventricle
Surfaces of the heart
Anterior Base Right pulmonary Left pulmonary Diaphragmatic
Anterior chamber of the heart is?
Right ventricle
Blood supply to the AVN and the SAN?
Right coronary artery
Left dominant heart is what?
If the posterior descending artery comes from the left coronary artery rather than the right coronary artery - 15% of people
Blood supply to the AVN and the SAN?
Right coronary artery
Three bundle branches of the LAD
Posterior/septal branch fo the left bundle
Right bundle
Left bundle
Bundle of His divides into what?
Right bundle
Left bundle
Bachman’’s bundle?
This is a bundle coming straight from the SAN
ECG presentation of AF?
Absent P waves
Causes of concentric hypertrophy x2
Aortic stenosis
Chronic hypertension
Why can concentric hypertrophy lead to eccentric hypertrophy?
Reduced compliance results in volume overload
Causes of ventricular hypertrophy x2
Aortic stenosis
Chronic hypertension
Cause of eccentric hypertropohy
Volume overload/preload
Valves open during systole
Aortic and pulmonary
Valves open during diastole
Mitral and tricuspid
S1-S2 systole or diastole?
Systole
S2-S1 systole or diastole?
Diastole
Two effects of rheumatic disease
Fibrosis of the valve cusps
Softening of the cordae tendinae
When is mitral regurgitation heart?
Systolic murmur
When is aortic stenosis heart?
Systolic murmur (mid-systolic)
Effect of mitral valve stenosis on left atrium?
Causes left atrial enlargement
When is mitral stenosis heard?
Diastolic murmur
Oedema in left sided heart failure?
Pulmonary oedema - respiratory crackles
Cause of eccentric hypertropohy
Volume overload/preload
Valves open during systole
Aortic and pulmonary
Valves open during diastole
Mitral and tricuspid
Parasympathetic outflow to the heart comes from which vagus nerve nuclei?
Mainly nucleus ambiguus - also some from from dorsal motor nucleus
S2-S1 systole or diastole?
Diastole
Two effects of rheumatic disease
Fibrosis of the valve cusps
Softening of the cordae tendinae
When is mitral regurgitation heart?
Systolic murmur
When is aortic stenosis heart?
Systolic murmur (mid-systolic)
Effect of mitral valve stenosis on left atrium?
Causes left atrial enlargement
When is mitral stenosis heard?
Diastolic murmur
Pathological/Inferior Q waves show?
Shows that the patient has had a previous AMI - very likely to suffer from heart failure
Oedema in right sided heart failure?
Systemic oedema - swollen ankles
Oedema in congestive heart failure?
Symptoms of both
CXR signs of pulmonary oedema?
Batwing sign
Kerley B lines
Define pulmonary oedema
Excess fluid in the lungs - at the base of the lungs
Is heart failure more common amongst men or women?
Men
Four causes of heart failure?
Coronary artery disease
Hypertension
Cardiomyopathy
Valvular heart disease
Anything that causes something to be wrong with the heart
Give four aggravating factors for heart failure
Cardiac arrhythmia e.g. AF
Hypertension
Anaemia
Infections
Symptoms of heart failure x3
Fatigue
Dyspnoea
Oedema
Signs of heart failure x8
Cool skin Peripheral cyanosis Basal crackles Increased JVP Ankle swelling Ascites Tachycardia Sweating
Give six potential complications of heart failure
Inttravascular thrombosis Infection Functional valvular dysfunction Multi-organ failure Cardiac arrythmias Sudden death
Three common ECG findings in heart failure
Inferior Q waves
Anterior T waves
Left bundle branch block
What should be present on an ECG for a patient to benefit from cardiac resynchronisation therapy (pacemaker)?
Prolonged QRS interval - >150ms (OR >120ms plus echo signs)
Effect of heart failure on the lungs
Patient has wet lungs - pulmonary oedema
Define pulmonary oedema
Excess fluid in the lungs
Gold standard investigation for heart failure is?
Echocardiogram
What is brain natriuretic peptide BNP?
Secreted by myocardial cells in response to raised left atrial pressure
Also secreted when ventricles are stretched
Functions of BNP x4
Promotes natriuresis and vasodilation
Inhibitors ADH and aldosterone release
Effect of pharmacological treatmetn on diastolic failure?
No proven value
Define pulmonary effusion
Collection of excess fludi in the pleural cavity - potential space becomes a real space
Main treatment groups for heart failure x2
Beta blockers - for sympatho-adrenal activation
ACE inhibitors, ARB, sprionolactone - for RAAS activation
Why are diuretics commonly given for heart failure?
For treatment of fluid retention
Indications for a heart transplant x4
Heart failure without the following: Major organ failure Major co-morbidity Psychological disability Severe pulmonary hypertension
Prognosis from heart transplant
80% one year survival (bad)
Diastolic vs systolic heart failure
Systolic - heart cannot contract effectively
Diastolic - heart cannot relax sufficiently to fill completely
Who is diastolic failure more common in? x2
Women
Older patients
Treatment of diastolic heart failure x3
Treat the underlying cause - especially hypertension
Treat the systolic component if mixed
Treat fluid retention
Effect of pharmacological treatmetn on diastolic failure?
No proven value
Define pulmonary effusion
Collection of excess fludi in the pleural cavity - potential space becomes a real space
Define cardiac myopathy
A disease of the heart muscle
Cardiac myopathy usually caused by what type of mutations?
Missense mutations
Four types of cardiomyopathy are?
Restrictive
Hypertrophic
Dilated
What is restrictive cardiomyopathy?
Lack of stretch/dilatation of the ventricles during diastole due to increased stiffness of the wall
Reduced compliance
Appearance of the heart in restrictive cardiomyopathy?
Heart appears normal visibly but does not stretch when required
What is pericarditis?
Inflammation of the pericardium
Hardening and lack of movement of fluid - restrictive disorder
Heart sounds present in restrictive cardiomyopathy?
Third heart sound and fourth heart sound
Hypertrophied cardiomyopathy is?
Hypertrophy of the myocytes - increase in size of the cardiac muscle of the ventricular wall
Mutations of hypertrophied cardiomyopathy?
Missense mutations
Main antihypertensive for under 55 year old
Ace inhibitor or ARB
First heart sound caused by?
Closing of the mitral and tricuspid valves
Second heart sound caused by?
Closing of the aortic and pulmonary valves
Cause of third heart sound?
Ventricular gallop
Cause of fourth heart sounds?
Atrial gallop
What is pericarditis?
Inflammation of the pericardium
Hardening and lack of movement of fluid - restrictive disorder
Main risk factor for CHD?
Atherosclerosis
Four main risk factors for CHD?
Hypertension
High cholesterol - atherosclerosis
Obesity
Diabetes
Lifestyle interventions to reduced CHD in hypertensives? x7
Smoking cessation Diet - reduce body weight Reduce salt intake <100 Reduced alcohol consumption Regular aerobic exercise Fruit and veg Reduce sugar intake
Target BP for hypertensives
<140/80
Second line antihypertensive?
Thiazide-like diuretic
Mortality rate for CHD?
50% of cardiovascular disease deaths
Calcium antagonist action and s/e
Vasodilation
Flushing and oedema
ACE inhibitor action and s/e
Inhibit RAAS and vasodilate
Cough and low BP
ARB action and s/e
Block action of angiotensin - vasodilate
Low BP
Function of folic acid in polypill
Reduce homocysteine
Quantity of aspirin in polypill?
75mg
Target BP for hypertensives with diabetes
<130/80
Two antihypertensives unsuitable for diabetics + why?
Thiazide diuretics
Beta blockers
Worsen glucose control
Treatment of MI x4
Humidified oxygen
Opiates
Aspirin
Thrombolysis/primary angioplasty
Secondary prevention for MI
Beta blockers
ACE inhibitors
Statins
Four components of polypill
Statin
Antihypertensives
Antplatelet aspirin
Folic acid
Function of folic acid in polypill
Reduce homocysteine
Quantity of aspirin in polypill?
75mg
Define autoantibodies
Antibodies that react to self antigens
Alloantibodies?
Antibodies that react to foreign antigens
Antigens on surface of RBC are?
Sugar - ABO blood type
Protein - Rhesus blood type
Protein/sugar antigen on RBC determined by?
Genes
Alloantibodies are dangerous when?
Exposed to another blood type e.g. pregnancy or transfusion
Sugar antigens present on RBCs?
A or B
A antigen on RBC - what antibody do you have?
Have anti-B antibody
What type of Ig are RBC antigens?
IgM or IgG
Agglutinate means?
Attach to the antigen to prevent it from binding to anything
Universal blood type donor?
Blood type O - not agglutinated by any antibody
Universal blood type acceptor?
AB blood type - have no antibodies in the plasma
Different rhesus blood types?
C or c
D or no D (no D is written as d)
E or e
Are antibodies produced against the rhesus blood types?
Not naturally produced - will be produced by immune system upon exposure
Temperature spike during transfusion indicates what?
Transfusion reaction - intravascular haemolysis
STOP transfusion immediately!!
cdE will be agglutinated by which antibodies?
Anti-c
Anti-E
Which rhesus antigen is the most clinically important and why?
D antigen
80% without D antigen will develop anti-D if exposed
CcDEe - rhesus D positive
Cde - rhesus D negative
Haemolytic disease of the newborn (HDN) is what?
Rhesus negative mother develops anti-D antibodies upon exposure
Rhesus positive second baby - stillbirth or severe brain damage
How is HDN prevented?
Rhesus negative mothers carrying rhesus positive babies are given prophylactic anti-D antibodies
Five risks of blood transfusion
Transmit infection Alloimmunisation - antibody can compromise future transfusion Incompatible transfusion Iron overload from multiple transfusions Circulatory overload
Purpose of indirect antiglobulin test?
Screen for atypical antibodies in the patient’s plasma
Temperature spike during transfusion indicates what?
Transfusion reaction - intravascular haemolysis
STOP transfusion immediately!!
Thrombosis vs. embolism
Thrombus - pathological clot formation
Embolism - part of clot breaks off and becomes obstructed in smaller vessels
Composition of venous vs. arterial thrombi
Venous thrombi - RBCs
Arterial thrombi - platelets
Two main types of venous thromboembolism (VTE)?
DVT
PE
Location of distal DVT?
Calf veins only
Location of proximal DVT?
Popliteal veins or above
Three main causes of VTE and what is this known as?
Virchow’s triad:
Reduced blood flow - stasis
Vessel wall disorder
Hypercoagulability
Four genetic risk factors for VTE
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Factor V Leiden
Six major risk factors for VTE
Fracture of the hip/pelvis Hip/knee replacement surgery Major general surgery major trauma Spinal cord injury Hospitalisation with acute medical illness
Four complications of DVT
PE
Extension of clot
Recurrent VTE
Post-thrombotic syndrome
Five weak risk factors for VTE
Bed rest>3 days Travel-related Obesity Day-case surgery Varicose veins
DVT presentation? x8
Pain Erythema Tenderness Swelling Palpable cord Warmth Ipsilateral oedema Superficial venous dilation
WHY IS IT SO IMPORTANT TO HAVE CORRECT DIAGNOSIS OF VTE?
90% of presenting patients do not have VTE and drugs can be fatal
What is D-dimer?
Fibrin degradation marker
Non-specific for clot formation
Investigations for DVT
D-dimer
Radiology e.g. ultrasound, CT
Scoring system used for DVT?
Wells score: >2 DVT likely and <1 unlikely
What is post-thrombotic syndrome?
Recurrent pain and swelling in the leg - venous hypertension
Three signs of PE
Tachypnoea
Tachycardia
Crepitations and pleural rub
Three main investigations for PE
ECG
CXR
Arterial blood gasses
Wells score for likely PE?
> 4
Other conditions that D-dimer may be raised in are? x4
Infection
Cancer
Inflammation
Pregnancy
Define thrombocytopenia?
Deficiency of platelets
Half life of LMWH?
4 hours
What is fondaparinux?
Anticoagulant
Half life of fondaparinux?
18 hours
When is fondaparinux unsuitable?
Patients with renal impairment
Three side effects of heparin?
Major bleeding - 1-5% of patients
Heparin induced thrombocytopenia
Osteoporosis - exposure over several weeks
Lifestyle treatment for VTE?
Graduated knee stockings
What is warfarin?
Vitamin K antagonist
Half life of warfarin
36 hours
Function of warfarin
Affects INR - reduces risk of recurrence by 90%
Who should warfarin not be used in?
Pregnancy - teratogenic
Two surgical interventions for VTE?
Thrombolysis
Inferior vena cava filter
Lifestyle treatment for VTE?
Graduated knee stockings
Define haemostasis
Stopping of blood flow
Vessel damage causes which two reactions?
Platelet release reaction
Coagulation cascade
Vasomotor change during vessel injury is what and why?
Vasoconstriction occurs - to reduced blood flow
What causes the vasoconstriction during vessel injury?
Serotonin
Function of vWF?
Adherence of platelets to one another and to teh sites of vascular damage
Factor that activates the coagulation cascade is?
Platelet phospholipid
Primary haemostasis is?
Formation of primary platelet plug via platelet aggregation and reduced blood flow
Secondary haemostasis is?
Coagulation cascade - stabilisation of primary platelet plug
What is Von Willebrand factor? vWF?
Glycoprotein in the plasma
Site of vWF synthesis?
Bone marrow and endothelial cells
Receptors for vWF on platelets?
Primary - GpIb
Secondary - GpIX, GpV
what is Von Willebrand disease?
Deficiency in/defective vWF - lack of ability to clot
Inheritance of Von Willebran disease?
Autosomal
Bernard Soulier syndrome is what?
Lack of GpIb
Glanzmann’s syndrome is what?
Lack of GpIIb
Platelet lifespan
8-14 days
Roles of glycoproteins
Receptors for adhesive proteins, coagulation factors and proteins
Three most abundant glycoprotein molecules
GpIIIa
GpIb
GpIIb
Treatment for VWD?
Desmopressin
DRAW OUT PATHWAY FROM ARUN
DRAW OUT PATHWAY FROM ARUN
Function of thrombin
Fibrinogen to fibrin
what is the activated partial thromboplastin time (APTT)?
Time taken for the intrinsic pathway of the coagulation cascade
Four components responsible for the regulation of coagulation
Antithrombin
Protein C
Protein S
Fibrinolytic clot
What is the thrombin time?
Time taken for the final common pathway of the coagulation cascade
Haemophilia A affects which factor?
VIII
Haemophilia B affects which factor?
IX
Five symptoms of haemophilia
Soft tissue bleeds Bleeding into joint cavities Psoas bleeding Intracranial bleeds Bleeding at operative sites
Function of protein C
Inactivates Va and VIIIa
What activates protein C?
Thrombin
Risk factors for DIC x6
Infection Malignancy Shock Liver disease Transmplantation Snake bite Intravascular haemolysis
Where is vitamin K produced?
Liver
What are the vitamin K dependent factors?
II, VII, IX, X
Disseminated intravascular coagulation (DIC) is what?
Underlying condition activates coagulation cascade - pathological blood clots
Risk factors for DIC x6
Infection Malignancy Shock Liver disease Transmplantation Snake bite Intravascular haemolysis
ECG - what shows HR?
RR intervals
PR interval shows?
Action potential from the atria to the Bundle of His
P wave shows?
Atrial depolarisation
HR normal range?
RR interval
60-100 bpm
P wave normal wave
80ms - 2 squares
RR interval shows?
HR
PR interval normal length?
120-200ms
QRS interval normal length?
<120ms
PR interval >200ms indicates?
Heart block
QRS complex shows?
Ventricular contraction
Normal HR?
60-100bpm
Normal P wave length?
<80ms
Sinus tachycardia is?
HR > 100bpm
Normal QRS duration?
<120ms
Sinus bradycardia is?
HR < 60bpm
Sinus bradycardia normally seen when?
In patients on beta blockers
Tachycardia is?
HR > 100bpm
Ventricular tachycardia is?
Very very high rate - 180-190bpm
Ventricular tachycardia on ECG?
No P wave
Ventricular tachycardia vs ventricular fibrillation?
Tachycardia - regular
Fibrillation - irregular
Ventricular fibrillation on ECG?
HIGH RATE - 300+!!!
Absent P wave
No QRS seen
First degree heart block?
PR interval - fixed constant duration >200ms
Second degree heart block type 1?
AKa. Wenkenbach
PR interval progressively longer - finally absent QRS
Regularly irregular
Second degree heart block type 2?
Irregularly regular rate- random absence of QRS
Third degree heart block on ECG?
Bradycardia
Ventricle contracts independently of atria
Inverted QRS
When is heart block present?
If the PR interval is >200ms
ECG of AF?
Cannot see P wave or PR interval
Cause of AF?
Many separate sites of the atria are generating electrical impulses
P wave inverted in which lead in junctional rhythm?
Inverted in lead II
ECG of Atrial flutter?
P wave replaced with multiple F waves
300bpm
What is junctional rhythm?
AVN takes over as the normal pacemaker
ECG appearance of junctional rhythm
Bradycardia
Normal QRS
Absent P wave (or inverted)
P wave inverted in which lead in junctional rhythm?
Inverted in lead II
Ventricular tachycardia is?
Very very high rate - 180-190bpm
Ventricular tachycardia on ECG?
No P wave
Ventricular tachycardia vs ventricular fibrillation?
Tachycardia - regular
Fibrillation - irregular
Ventricular fibrillation on ECG?
HIGH RATE - 300+!!!
Absent P wave
No QRS seen
First degree heart block?
PR interval - fixed constant duration >200ms
Second degree heart block type 1?
AKa. Wenkenbach
PR interval progressively longer - finally absent QRS
Regularly irregular
ELECTRICAL AXIS OF THE HEART LOOK AT
ELECTRICAL AXIS OF THE HEART LOOK AT
Third degree heart block on ECG?
Bradycardia
Ventricle contracts independently of atria
Inverted QRS
When is heart block present?
If the PR interval is >200ms
ECG of AF?
Cannot see P wave or PR interval
Cause of AF?
Many separate sites of the atria are generating electrical impulses
Cause of Atrial flutter?
SAN firing too fast - prior to completion of ventricular contraction
ECG of Atrial flutter?
P wave replaced with multiple F waves
300bpm
What is dextrocardia?
Where the primiive heart folds to the left instead of right - the heart (apex) is on the right side of the body rather than the left
Aorta loops towards the right
ECG appearance of junctional rhythm
Bradycardia
Normal QRS
Absent P wave (or inverted)
P wave inverted in which lead in junctional rhythm?
Inverted in lead II
What is supraventricular tachycardia?
Tachycardia generated in the atria
What are endocardial cushions and what do these become?
Four areas of growth in the heart
Become the mitral and tricuspid valve - two each
Most common supraventricular tachycardia is?
AVNRT
AVNRT more common in men or women?
Women
ECG appearance of a bundle branch block? x2
Prolongation/widening of the QRS complex
Notch on the R wave or double R wave
What is represented by the ST segment?
The time during which both ventricles are fully depolarised
Charge of the ST segment is?
Isoelectric
Downsloping/depressed ST segments indicative of what? x2
Coronary ischaemia
OR
Hypokalaemia
Diagnosis of STEMI requires what from an ECG trace?
New ST elevation in two or more adjacent ECG leads
NSTEMI indicates what?
Cardiac ischaemia
ELECTRICAL AXIS OF THE HEART LOOK AT
ELECTRICAL AXIS OF THE HEART LOOK AT
Primitive heart tube forms/completes on what day of development?
21
Heart starts to beat on what day?
22
What is an atrial septal defect likely to be caused by?
Lack of development of the septum primum or the septum secondum
Bulbus cordis becomes what?
Right ventricle
Heart tube doubles in length at which day of development?
Day 22 to day 24
Why does the heart loop when lengthening?
Contained within pericardial sac
What is dextrocardia?
Where the primiive heart folds to the left instead of right - the heart (apex) is on the right side of the body rather than the left
What situs inversus?
Organs are all in the reversed region
Prevalence of situs inversus?
1:7000
What is the AV canal during development adn what does this become?
Communication between atria and ventricles - becomes the mitral and tricuspid valves
What is a cyanotic heart lesion?
Lesion with a shunt going from right to left - deoxygenated shunted to the left adn merges with oxygenated blood
Teratalogy of fallt
Transposition
Truncus arteriosus
What is an acyanotic heart lesion?
Lesion where oxygenated blood joints deoxygenated blood
ASD
VSD
PDA
Coarctation
What are the four characteristics of the teratalogy of fallot?
Overriding aorta
Right ventricular hypertrophy
Ventricular septal defect
Narrow RV outflow
What is the significance of the endocardial cushions in embryology?
Abnormalities can often occur here - cardiac malformations form
What day does atrial partitioning occur and how?
Day 28
Septum primum
What is at the free edge of the septum primum?
Ostium primum
Where is the foramen ovale in teh developing heart?
Septum secondum
What is the function of the foramen ovale?
Shunting of blood from th right atria to the left atria
Why do you require the foramen ovale in teh developing heart?
The foetus does not use it’s lungs
What is the septum primum and it’s function?
Acts as a flap/valve over the foramen ovale
How does the foramen ovale close following birth?
Increaed pressure in the left atrium - septum primum pushes up against septum secondum adn they seal
What is the remnant of the foramen ovale known as in adults?
Fossa ovale
What is an atrial septal defect likely to be caused by?
Lack of development of the septum primum or the septum secondum
When do the ventricles start to form in the developing heart?
End of the 4th week
Umbilical arteries - how many and what do these carry?
There are two of these from foetus to placenta
Carry deoxygenated blood
Umbilical veins - how many and what do these carry?
One of these
Placenta to baby
Oxygenated blood
What does the umbilical vein become at birth?
Ligamentum teres of the liver
Umbilical arteries and veins are under high or low pressure?
High
What is the ductus arteriosus?
Connects the pulmonary artery to the descending aorta
What causes the ductus arteriosus to close?
Increased paO2
What is a cyanotic heart lesion?
Lesion with a shunt going from right to left - deoxygenated shunted to the left adn merges with oxygenated blood
What is an acyanotic heart lesion?
Lesion where oxygenated blood joints deoxygenated blood
What are the four characteristics of the teratalogy of fallot?
Overriding aorta
Rijt ventricular hypertrophy
What is a persistent truncus arteriosus?
Single artery arises from the heart - supplies both aorta and the pulmonary artery
How does persistent truncus arteriosus present?
Progressive heart failure
What is meant by transposition of the great vessels?
Right ventricle pumps into the aorta and the left ventricle pumps into the pulmonary artery
What is teh presentation of the transposition of great vessles and what should be done?
BLUE BABY
Immediate surgical intervention
Three symptoms of atrial septal defects
Exercise intolerance
Dyspnoea on extertion
Fatigue
What is the most common cardiac defect?
Ventricle septal defect - 25%
What are atrial and ventricular septal defects?
Opening between teh two atria/the two ventricles
What is a patent ductus arteriosus?
Connection between descending aorta and the pulmonary trunk
Treatment of patent ductus arteriosus?
Prostaglandin inhibitor e.g. ibuprofen
Then surgery
Treatment for coarctation of the aorta
Balloon angioplasty
Medical term for breathlessness is?
Dyspnoea
Define breathlessness
Undure awareness of breathing or awareness of difficulty breathing
Two respiratory centres adn where are these located?
Pneumotaxic centre
Apneustic centre
In the pons
Nerve groups involved with breathing and what do these innervate? x2
Phrenic nerve - diaphragm
Intercostal nerves - intercostals
Ten causes of breathlessness
Hypoxia Metabolic acidosis Hypotension/reduced CO Pulmonary oedema Obstruction of the pulmonary artery Anaemia Exercise Pregnancy Anxiety, pain Breathing CO2
Hormone involved in pregnancy causing breathlessness
Progesterone
Receptors involved in metabolic acidosis causing breathlessness
Peripheral chemoreceptors
Receptors involved in the lungs causing breathlessness during pulmonary oedema are?
J receptors
Six associated factors for breathlessness
Smoking Hypertension DM Hyperlipidaemia Obesity Family history
What is meant by ‘shunting’?
An area of the lung that is perfused but is not ventilated
Most important sign of respiratory failure and why?
Tachypnoea - >25 adn definately >30
This is the first sign to appear - all the others appear late
Define tachypnoea
Abnormally rapid breathing
Ten signs of respiratory failure
Tachypnoea Use of accessory msuscles Nasal flaring Intercostal or suprasternal recession Tachycardia Hypertension Sweating Cyanosis Flapping tremor Boundign pulse
Type 1 respiratory failure is?
Hypoxaemia only (and hypocapnia) PaO2 < 8kpa
Type II respiratory failure is?
Hypoxiaemia and hypercapnia
PaO2 < 8kPa
PaCo2 >6.5kPa
Cause of type I respiratory failure is?
Due to damage to the lung tissue - prevents adequate perfusion of the tissue but can still excrete Co2
Cause of type II respiratory failure is?
Ventilatory failure - alveolar ventilation is insufficient to excrete the Co2 being produced
Four examples of type I respiratory failure
Pneumonia Pulmonary oedema Asthma/COPD PE Pneumothorax
Main of type II respiratory failure
Hypoventilation e.g. airway obstruction, nerve trauma
First line treatment for respiratory failure?
Provide O2
Second line treatment of respiratory failure? x2
Control secretions
Treat lung infection - antibiotics
Final line of treatment for respiratory failure?
Respiratory support - invasive OR non-invasive
Three types of oxygen delivery masks?
Oxygen masks - nasal cannulae
Face mask with resevoir bag
Venturi mask
Indication for use of oxygen mask with nasal cannulae?
Patient with normal vital signs e.g. post-op
Indication for use of face mask with reservoir bag?
High O2 concednration needed by patient
E.g. asthma attach, pneumonia, sepsis
Indication for use of venturi mask?
Controlled treatment required in long term respiratory failure e.g. COPD
Oxygen saturation level required in human?
SpO294%
What does pulse oxometre tell you?
Oxygenation of patient - not ventilation
Five sources of error with pulse oximetry?
Poor peripheral perfusion Dark skin - over reads False nails/nail varnish Bright ambient light Lipidaemia
Desired partial pressure of O2?
PaO2 > 10kPa
If unsure of the cause of respiratory failure in the patient, what treatment should you administer whilst coming to a diagnosis?
High flow oxygen
What is the volume for the tidal volume?
Half a litre
Three factors that affect vital capacity
Age
Height
Sex
Best method to analyse obstructive diseases?
Peak flow
When should peak flow be measured?
Once in morning, once in evening
Indication of asthma severity via peak flow?
The greater the peak flow difference between morning and evening, the more severe the asthma
Define vital capacity
Volume from maximum expiration to maximum inspiration
How to measure forced expiratory volume?
Vitalograph
What is a vitalograph?
An electric peak flow metre
Obstructive vs restrictive lung disease on a vitalograph?
Obstructive - FEV1 is reduced due tot eh narrow airways but the FVC will be the same
Restrictive - FEV1 AND FVC are reduced
FEV1/FVC ration in obstructive and restrictive disease?
Obstructive - ratio is reduced
Restrictive - ratio is teh same (both reduce)
When plotting from vitalograph, what is on each axis?
Y axis - volume, l
X axis - time, s
FEV1/FVC ratio showing no obstruction?
> 70%
FEV1/FVC ratio showing mild obstruction?
61-69%
FEV1/FVC ratio showing moderate obstruction?
45-60%
FEV1/FVC ratio showing severe obstruction?
<45%
Smoking causes what type of lung disease?
Obstructive
Key test result for obstructive disorders is?
Reduced peak flow rate
Key test result for restrictive disorders is?
Reduced vital capacity
Two main obstructive disorders are?
Asthma
COPD
Three characteristics of asthma?
Reversible airway obstructive
Hyper-responsiveness of airways
Atopoic
Three key features of the pathophysiology of asthma?
Bronchoconstriction
Secretion of mucous
Airway inflammation
What is the cause of asthma?
Oversupplied IgE receptors
Immediate response of asthma pathophysiology?
Inhaled allergens bind to Ige on mast cells and release inflammatory mediators - histamine
Effect of inflammatory mediators/histamine released in asthma?
Increased mucous secretion
Bronchonconstrction
Oedema
Asthma delayed response is?
Mast cells activate eosinophils and release proteisn to damage epithlial cells
Common protein released by eosinophils in asthma is?
Eosinophil peroxidase
Function of proteins released by eosinophils in asthma?
Damage to epithelium - stimulate afferent nerves
Activation of parasympathetic nerves - muucous secretion and airway constriction
What autonomic control is involved in asthma?
Parasympathetic
Why is there a build up of mucous in an asthmatic?
Increased mucous secretion BUT damaged epithelium SO cannot clear the mucous
Four substances that can trigger asthma
Dusts
Polles
Medications
Food
Five symptoms asthma
Troublesome cough - at night/after exercise Wheezing Chest tightness after exposure Colds last more than ten days Relief upon medication usage
Two key tests to diagnose asthma?
Peak flow
FEV1/FVC measuremetn
Three long term medications to treat asthma
Inhaled corticosteroids
LABA - long acting beta-2 agonists
Leukotriene modifiers
Function of long term medications x3
Reduce inflammation
Relax airway muscles
Improve lung function
Quick relief asthma medication and function
Short acting beta-2 agonists
used in acute episodes
Advantage of spacers?
Improve penetration of the drug into the lung
Reduce potential adverese effects from occurring
Indications for use of nebulisers for asthma treatment?
Small children
Severe asthma episodes
COPD is a combination of?
Chronic bronchitis
Emphysema
Time period for bronchitis to become diagnosed?
Chronic productive cough for more than half the time over two years
Main cause of emphysema?
Smoking
Main structure present in emphysema?
Bullae
Pathophysiology of bronchitis?
Proliferation of squamous cells
Massive mucous gland enlargment
Enzyme involved in emphysema?
Serine elastase
What is inactivated in emphysema?
Elastase inhibitor alpha-antitrypsin
Steroids are useful in the treatment of which obstructive lung disease?
Asthma
Four restrictive disorders of the lung?
Pneumonia Pneumothorax Pulmonary fibrosis Pleura thickening Ankolysing spondylitis
Normal PaO2
95
Normal PaCo2
40
Normal PaHCO3-
24
PvO2 (venous blood gas)
30-40
PvCO2?
50
What is respiratory acidosis?
Build up of CO2 in the blood - reduces pH
Five main causes of respiratory acidosis
Hypoventilation - drugs Diseases of the airways - asthma Diseases of the chest - scoliosis Disease affecting nerves/muscles Severe obesity - restricted expansion of the lungs
pH is controlled by the ratio of what?
HCO3-/CO2
Respiratory acidosis effect on pCO2 and HCO3-?
CO2 increases a lot
HCO3- increases slightly
Eight symptoms of respiratory acidosis?
Headache Drowsiness Lethargy Anxiety Sleepiness Fatigue Memory loss Restlessness Muscle weakness
Five signs of respiratory acidosis?
Slowed breathing Gait disturbance Tachycardia Tremor Reduced BP Papilledema
What is the main cause of the signs and symptoms from respiratory acidosis?
Due to a low CNS pH - causes reduced cerebral blood flow
What is the cerebral blood flow dependent on?
Dependent on plasma pH i..e CO2
pH and pCO2 in respiratory acidosis?
pH <7.35
pCO2 >45mmHg
Treatment for respiratory acidosis
Oxygen
Bronchodilators
Stop smoking
Treat underlyign lung condition
Effect of respiratory acidosis on the kidneys and consequence of this?
Retention of K+ by the kidneys - hyperkalaemia
Effect of respiratory acidisos on the heart and why?
Respiratory acidosis causes hyperkalaemia
This causes heart arrythmias - disrupts resting potential
Acute respiratory acidosis test results?
PaCO2 > 6.3kPa/47mmHg and pH <7.35
Chronic respiratory acidosis test results?
PaCo2>6.3kPa/47mmHg
BUT pH is normal/near normal
High HCO3-
Acute vs. chronic respiratory acidosis?
Acute - reducded pH
Chronic - nromal pH due to renal compensation
Cause of respiratory alkalosis?
Hyperventilation
Four symptoms of acute respiratory alkalosis?
Hyperventilation Dizziness Light headedness Confusion Cramps
Five other acuses of respiratory alkalosis?
Meningitis Stroke Anxiety Cirrhosis Sepsis Hypoxia
Symptoms of chronic respiratory alkalosis?
Generally symptomless
Three matbolic changs in respiratory alkalosis?
Constriction of cerebral blood vessels
Increased neuromuscular activity
Hypoklaemia
Blood test results for respiratory alkalosis
pH > 7.44
PaCo2 < 35mmHg
Type I respiratory failure is?
Hypoxia with normal or low PCO2
Type II respiratory failure is?
Hypercapnia with or without hypoxia
What is the more common type of respiratory failure?
Type I
Ventilation/perfusion mismatch occurs in whcih type of respiratory failure?
Type I
Anion gap in rspiratory acidosis?
High
CO2/HCO3 ratio in respiratory acidosis?
High
CO2/HCO3 ratio in respiratory alkalosis?
Low
What is dependent on the CO2/HCO3 ratio?
pH
What is meant by ‘shock’?
Inadequate maintainance of CO
Cells involved in innate immunity are? x4
Neutrophils
Monocytes
Eosinophils
Mast cells
Cells involved in adaptive immunity are? x2
B adn T lymphocytes
What are the two main features of the adaptive immune system?
Self-tolerace
Memory
Clonal deletion is?
Deletion of B or T lymphocytes expresseing receptors for self antigens
Clonal expansion is?
Proliferation of B or T lymphocyte once it binds to foreign antigen
Which lymphocytes mature in the thymus?
T-lymphocytes
Function of IgG?
Block pathogen binding
Activate complement
Opsonise antigen for phagocytes
Role of IgG in pregnancy?
Specially transported across the placenta
Function of IgM?
Block pathogen binding, activate complement
Function of IgA?
Block pathogen binding
NB. no activation of complement
Where is IgA found?
Tears
Digestive juices
Function of IgE?
Activation of MAST cells
Function and secretion of IgD?
Both of these are unknown?
Proteins generated via complenet? x2
C3a
C5a
Role of histamine in type 1 hypersensitivity?
Increased permeability of venules
Vasodilation of arterioles
Itch
Contraction of smooth muscle - bronchial tree
Role of leukotrienes in type 1 hypersensitivity?
Increased permeability of venules
Chemotaxis
Role of prostaglandins in type 1 hypersensitivity?
Arteriolar dilatation
Pain
Fever
Cells activated in type I hypersensitivity?
MAST cells
Five clinical manifestations of anaphylactic shock
Drop in blood pressure Warm peripheries Urticaria - hives Erythema Sore red itchy eyes Swelling of face, lips, hands, feet Bronchoconstriction Nuasea and vomiting Headache Cardaic arrest Death
Four antigens that can trigger anaphylaxis
Drugs - penicillin, beta-lactams, NSAIDS, aspirin Latex Foods - peanuts, fish Arthropon venoms Exercise can predipose
Acute treatment of anaphylaxis x5
Intramuscular adrenaline - 500mg Oxygen high flow Fluids iv Antihistamines Glucocorticoids
What is omalizumab and why is this not used?
Monoclonal antibody against IgE
Very very expensive and impractical - intravenous injections lifelong
Interleukin involved primarily in allergens and shock?
IL4
Main significance of lower respiratory tract infections?
One of three most important infective causes of death in children under the age of 5
Five bacteria causing respiratory tract infections
Streptococcus pneumonia Haemophilius nfluenza Staphylococcus aureus Streptoccus pyogenes Mycoplasma pneumonia
Two viruses causing respiratory tract infections
Influenza
Respiratory syncytial virus (RSV)
Protozoa causing respiratory tract infections and in who?
Toxoplasma gondiii
In the immunocompromised
Community acquired pneumonia occurs in who typically?
Very young and very old
Also those with co-morbidities
Pathogens taht can cause community acquired pneumonia are grouped into which two groups?
Typical OR atypical pathogens
What can community acquired pneumonia be secondary to?
Viral respiratory tract infection
How frequently can the cause of community acquired pneumonia not be identified?
40-60% - even after extensive testing for known respiratory pathogens
How common is hospital acquired pneumonia in the world?
Third commonest nosocomial infection
What is the mortality rate of hospital acquired pneumonia?
Nosocomial infection with the highest mortality rate
Five risk factors for hospital acquired pneumonia
Abnormal conscious state Intubation Ventilation Surgery Immunosuppression
cteria type typically causing hospital acquired pneumonia is?
Gram negative
Most common cause of typical lobar pneumonia - community acquired?
Streptococcus pneumoniae
Typical presentation of community acquired pneumonia? x4
Sudden onset of chills
Fever
Pleuritic chest pain
Productive cough
Investigation to identify S. pneumoniae?
Gram stain of sputum
Presentation of atypical pneumonia?
Non-productive cough
Fever
Headache
Chest x-ray is more normal than typical pneumonia
Top five organisms causing atypical penumonia
Mycoplasma pnumonia - most common Chlamydia pneumoniaae C.pittaci Legionella pneumophilia Coxiella burnetti
Mycoplasma pneumonia - how is this transmitted?
Droplet infection
Mycoplasma pneumonia who does this typically occur in?
School age children and young adults
Symptoms of M.pneumoniae?
Fever Headache Myalgia Earache Dry cough
Oragnism causing Q fever
Coxiella Burnetti
Three typical complications associated with pneumonia are?
Pleural effusion
Empysema thoracis
Lung abscess
Hospital acquired pneuminia occurs in whom?
Immuno-compromised patients
What is the mortality rate of hospital acquired pneumonia?
20-50%
What is the CURB65 score used for?
TO determine who requires treatment for pneumonia
What does CURB65 stand for?
C - confusion U - urea >7mmol R - respiratory rate >30 B - blood pressure <90mmHg 65 - age >65
Increased risk of death as the score increases - score 0-5
CURB-65 score of 0 equates to?
Low risk of death - do not require hospitalisation
CURB-65 score of 1/2 indicates?
Increased risk of death - consider hospitalisation
CURB-65 score of 3+ indicates?
High risk of death - requires urgent hospital admission
Treatment for community acquired pneumonia?
Beta lactams
Risk of death with CURB-65 score of 0?
0.7%
Risk of death with a CURB-65 score of 5?
57%
Which community acquired pneumonia pathogen should not be treated with beta lactams?
M. pneumoniae
Pathogen that causes TB is?
Mycobacterium turburculosis
Five symptoms of TB?
Dry cough Poor appetite Weight loss Weakness Fever
M. turburculosis gram negative or positive?
Negative
What is the Mantoux test?
To identify TB immunology
Vaccine protecting against TB?
BCG
Efficacy of BCG vaccine against TB?
60-80% <16y/o
What is the upper respiratory tract?
Nose, paranasal sinuses, middle ear, nasopharynx, oropharynx, laryngopharynx, tonsils, adenoids
Four most common infections of the upper respiratory tract are?
Colds
Pharyngitis - sore throat
Tonsilitis
SInusitis (adults)and otitis media (children)
Most common pathogen group responsible for upper respiratory tract?
Viruses
Four most common virsuses causing upper respiratory tract infections?
Adenovirus
Parainfluenza virus
Respiratory syncytial virus
Rhinovirus
Virus most responsible for colds?
Strains of rhinovirus - 50%
Bacteria most responsible for URTIs?
Group A strep - pharyngitis
Significance of epiglottitis?
This is a medical emergency
Three symptoms of epiglottitis
Fever
Sore throat
Dysphagia
Rapid onset of these
ORganism group mostly responsibel for epiglotttitis
bacteria
Organism responsible for Whooping cough?
Bordetella Pertussis
Treatment for whooping cough?
Erythromycin
Bordetella Pertussis positive or negative gram staining?
Negative
Pathogen causing glandular fever?
Epstein Barr virus
Which organs enlarge in EBV?
Hepatosplenomegaly
Intercostal muscles are innervated by which nerves?
Anterior rami of thoracic spinal nerves
Where is the intercostal VAN found in the anterior thoracic wall?
Between the intercostal and the innermost intercostal muscles
Define thoracocentesis?
To sample the pleural fluid
Where is the needle inserted in the thoracentesis and why?
Superior to the rib to avoid damage to teh nerves (intercostal)
What level is thoracocentesis carried out
9th mid-axillary line
Where is a chest drain inserted?
5th intercostal space - mid-axillary line
Innervation of diaphragm is?
Phrenic nerve C3, 4, 5
Three muscles of inspiration
External intercostal
Diaphragm
(Also internal intercostal but only to a small degree)
Two accessory muscles of inspiration are?
Sternoceidomastoid
Scalene muscles
Muscle/mechanism of expiration is?
Elastic recoil
Muscles that carry out forced expiration? x2
Internal intercostal
Abdominal muscles
Nerve root of phrenic nerve
C3, 4, 5
Nerve roots of intercostal nerves
T2 - T12
Nervous innervation to the parietal pleura?
Intercostal nerves
Nervous innervation to the visceral pleura?
Sympathetic trunk and parasympathetic vagus
Nervous innervation to the diaphragmatic pleura?
Phrenic nerves
Bronchial tree is included in which pleural type?
Visceral pleura
Normal CXR - is the pleura of the lungs visible?
No
Lung apex is at what level?
2cm above the clavicle
Cardiac notch is at what level?
4th rib
Where does the vena cava leave the diaphragm?
T8
Where does he oesophagus leave the diaphragm?
T10
Where does the aorta leave the diaphragm?
T12
What are the pleural boundaries?
T8, T10, T12
Divisions of the bronchial tree are? x7
Trachea - main bronchi - lobar bronchi - segmental bronchi - terminal bronchioles - conducting bronchioles - respiratory bronchioles
Emphysema is ?
Ddestruction fo the avleolar walls - permenant enlargement of air spaces
Cartilage shape in teh trachea?
C shaped rings
Cartilage shape in teh bronchi?
Plates - all the way around
Cartilage shape in the bronchioles?
No cartilage in the bronchioles
Superior mediastinum is found above which landmark?
Angle of Louis
Function of recurrent laryngeal nerve?
Vocal cord innervation
Hoarsness of voice - damage to which nerve?
Recurrent laryngeal nerve
Recurrent laryngeal nerve loops around which structure? - left and right
Arch of the aorta - left
Subclavian artery - right
Long thoracic nerve supplies what?
Serratous anterior muscle
When are lung tumours felt and why?
Once they reach teh parietal pleura
The visceral pleura has no sensory innervation
Blood supply and drainage of lungs?
Bronchial arteries and bronchial veins
Origin of bronchial arteries?
Descending aorta
Bronchial veins drain to?
Azygous and hemi-azygous veins
The pulmonary trunk is?
Blood vessel from the right ventricle - bifurcates into the left and right pulmonary arteries
Trachea is where is relation to teh oesophagus?
Trachea is anterior to the oesophagus
Level of the dome of the left diaphragm is?
Lower boarder of the 5th rib
At what level does the vagus nerve perforate the diaphragm?
With the oesophagus - T8
Through the oesophageal hiatus
Anterior intercostal arteries originate from where?
The internal thoracic artery
Two terminal branches of the internal thoracic artery?
Superior epigastric artery
Musculophrenic artery
Superior epigastric artery originates from where?
Internal thoracic artery
Three effects of the sympathetic innervation to the bronchi, bronchioles and pulmonary vessles?
Bronchodilation
Vasoconstriction
Inhibition of glandular secretion
Three effects of parasympathetic innervation to teh bronchi, bronchioles and pulmonary vessles?
Bronchoconstriction
Vasodilation
Stimulation of glancular secretion
Three functions fo the diaphragm
Separate abdominal and thoracic cavities
Inspiration
Expiration
Muscle type of the diaphragm?
Skeletal
Nerve type of teh phrenic nerve?
Mixed - somatic and autonomic
Origin of intercostal arteries?
Internal thoracic artery
Intercostal veins drain to where?
Anterior - intenral thoracic vein
Posterior - azygous adn hemiazygous
Pleural reflection is?
Extent of the lung pleura whcih the lung does not extend to
Position of trachea in tension pneumothorax?
AWAY from the affected side
What si teh most preferred orientation of a CXR?
PA - posteriro to anterior
Why is PA CXR preferred?
Can accurately comment on size of the heart
When might you use an AP CXR?
Bed bound patietn
What is teh problem with an AP CXR? x3
Heart appears larger
Scapula is over the lung field
Clavicles are horizontal
Trachea will be deviated away from? x2
Mass
Tension pneumothorax
Trachea will be pulled towards? x4
Collapsed lung
Loss of lung volume
Consolidation
Fibrosis
Consolidation of the lung appears as?
Dense (white) material
Four causes of consolidation are?
Pneumonia
Haemorrage
Fluid - pulmonary oedema
Cells - cancer
Anything increasing teh density
Characteristic features of pneumothorax on CXR? x2
Asymmetrical
Lack of lung marking to the edge of the lung field
Pleural effusion is?
Collection of fluid in the pleural space - lowest part
Recognise pleural effusion from CXR?
White
Meniscus
Abnormal cardiothoracic ratio is?
> 50%
What is below right dome of diaphragm?
Liver
What is below left dome of diaphragm?
Bowel
Emphysema on CXR visible when?
More than 6 anterior ribs/more than 8 posterior ribs
Flattening of hemidiaphragm
Five signs of congestive cardiac failure?
Alveolar oedema Kerly B lines Cardiomegaly - boot shaped Upper lobe divisions Bilateral effusions
Anterior vs. posterior ribs CXR
Posterior - attached to the sternum
Move forwards and become teh anterior ribs
Diapghram at the level of which rib?
7
Two causes of emphysema
Smoking
Air pollution
Three risk factors of TB?
HIV
Diabetes
Smoking
Four symptoms of pneumonia?
Cough
Fever
Dyspnoea
Chest pain
Horner’s syndrome is what?
Daamge to sympathetic nerves
Horner’s syndrome caused by tumour at whch part of the lung?
Apex
Signs of Horner’s syndrome
Constricted pupil (meiosis)
Drooping upper eyelid (ptosis)
Local inability to swear on ne side of teh face
Three features of asthm
Hypertrophy fo airway wall muscle - decreased lumen
Increased mucous production
Inflammatory cell infiltration
Two main symtptoms of asthma
Producing a wheeze cough
Breathlessnes
DDx for wheeze?
Infection
Asthma - allergens activate what cells?
Th2 cells
Th 2 cells asthma - these release what?
IL4
IL4 of asthma activates what?
B cells and MAST cells
Interleukins that activate B cells in asthma are? x2
IL4
IL13
Interleukins that activate Mast cells in asthma are?
IL4
IL6
IL9
Immunoglobulin in asthma activates what?
IgE activates Mast cells
Action of B cells in asthma?
Production of IgE - activates Mast cells
Four inflammatory components released by mast cells?
Histamine
PGD3
LTC4
Kinins
Summarise pathogenesis of asthma
ALlergens activate Th2 Th2 activates B cells and MAST cells B cells produced IgE IgE activates Mast cells, along with Il4 Mast cells release inflammatory mediators
Function of inflammatory mediators in asthma? x4
Activate nerve endings
Make mucous
Produce airway oedema
Bronchoconstriction
Four triggers for asthma
Allergens
Irritants
Infection
Exercise
Two DDx for wheeze when not asthma
Brnchiolitis - children
COPD
Bronchodilator treatment for asthma causes FEV1 to increased by how much?
15% / 200ml
Asthma attack - vital capacity increases or decreases?
Decreases
ASthma - airway resistance is greatest where?
In the larger airways
Asthma - compliance increases or decreases and why?
Increases - reduced alveolar elastic recoil
What is peak flow?
Person’s maximum speed of expiration
Peak flow morning vs/ evening
Wrose in teh morning adn better in teh eveing
Significance of peak flow in asthmatic?
Difference between morning and evening is greater in asthmatic
Airflow through a tube is dependent on which four variables?
Radius of the tube
Viscosoty fo the gas
Pressure difference across teh tube
Length fo teh tube
Four stimulus challenges to monitor asthma?
Histamine challenge
Metacholine challenge
Allergen challenge - risky
Cold air
What is the reason for challenge testing in asthmatic?
To see which stimuli the asthmatic responds to
What is reactive airways dysfunction syndrome RADS?
Bronchial hyperreactivity following infection - set off by irritants
Does RADS involve reacting to an allergen?
No
Untreated asthma over time has what effect on teh bronchi?
Chronic narrowing of the bronchi
Five common allergens for asthma?
Dust Grass Tree pollen Pet fur Urine
Three common irritants for asthma?
Sulphur dioxide
Nitrogen dioxide
Ozone
Whic infection isthhas the worst effect on asthma?
Viral infection
Why can exercise cause asthma?
Exercise - increased ventilation - cooling - cooling causes spasm
Significance fo asthma at night?
Asthma gets worse at night
Two main reasons asthma is worse at night?
Allergens in teh bed?
Did teh patient take their inhaler at night?
Menstrual asthma affects what percentage of women?
30%
Poor control of asthma can result in what?
COPD
First line treatmetn for asthma
Salbutamol as required
Second line treatment for asthma
Regular inhaled steroids
Fourth line treatment for asthma?
theophyllines
Leukotrient antagonists
Last line treatment of asthma
Oral steroids
Anti-IgE therapy
Steroid sparing agents
Treatment for acute severe asthma?
Immediate treatment with inhaled high dose bronchodilators, oxygen adn steroids
Acute severe asthma causes how many deaths per year?
1200
Two ways smoking leads to asthma
Increases NFkB
Blocks steroid response HDAC2
Prevalence of asthma in children
20%
Prevalence of asthma in adults
15%
Normal respiratory rate is?
<25 per minute (6-28)
Main facotor that can cause a change in respiratory rate?
Equipment usage e.g. mouthpieces
Most common test for measurement of lung function?
Spirometry
Normal FEV1/VC result?
75% FEV1/VC ratio
FEV1/VC ratio for obstructive lung disease?
<75%
FEV1/VC ratio for restrictive lung disease?
75% (reduced FVC)
SO >75% ratio
What is the Fick principle?
Volume of gas per unit time which diffuses across a tissue sheet is prportional to teh area of teh sheet
Inversely proportional to the thickness
Fick principle is dependent on?
Permeability coefficient for the gas that is diffusing
Graham’s law is?
The rae of diffusion of a gas is inversely proportional to the square root of it’s molecular weight (big things diffuse slower)
Four components that reduces gas transfer?
Reduced surface area
Increased thickness fo teh memrbrane
Reduced oxygen concentration
Inadequate time for gas transfer to occur
Pathogen responsible for majority of TB cases?
Mycobacteria tuberculosis
Five bacteria that cause TB
M. tuberculosis
M. bovis
M. microti
M. canetti
Mycobacteria that does not cause TB?
M/.avium complex
Four factors affecting likelihood of TB inheritance
Infectiousness of the person with TB
environment in which exposure occurs
Length of teh exposure
Virulence (strength) of teh tubercle bacilli
Pharmacological treatmetn for TB x4
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
How long should Ethambutol be provided for the treatmetn of TB?
2 months
How long should Rifampicin adn Isoniazid be provide for the treatmetn of TB?
4 months
What is DOTS in TB therapy?
OTS - directly observed therapy
This is used if you think that the patient is not likely to follow the therapy as they should
Why does hypoxia occur at high altitude?
PaO2 is reduced at high altitude so lungs are less saturated with oxygen
The drive to increase ventilation is suppressed by chemoreceptors to prevent teh excess loss of Co2
Hypoxic drive controlled by which site?
Carotid bodies
Hypoxic drive kicks in at what concentration of O2?
PO2 <60mmHg
what happens if there is a rapid ascent to high altitude?
Pulmonary circulation reacts to hypoxia with vasoconstriction - worsens the case of hypoxia SO pulmonary arterial hypertension
At what altitude will affects of hypoxia start to occur?
200m
People without respiratory disease can eventually acclimatise to what altitude?
2000-6000m
what altitude is regarded as the death zone?
7500m
Majority of time that can be spent in teh death zone is?
2-3 days
Significant hypoxia occurs at which altitude, even in the most experienced climbers?
7000m
What are the three components that occur during acclimatisation?
Metabolic acidosis
Increased erythrocyte number - increased haematocrit
Reduced pulmonary vascular resistance
Why does metabolic acidosis occur at high altitude?
To compensate for the respiratory alkalosis - reduced renal excretion of acid
How is haematocrit increased at high altitude?
Increased production of EPO
How can increased haematocrit prove to be fatal?
Increased haematocrit can increase teh viscosity of the blood which can lead to increased pulmonary vascular resistance adn lead to pulmonary arterial hypertension
Rigth heart failure
Effect of high altitude on pulmonayry vascular resistance?
Increaes
What happens to the pulmonary vascular resistance upon acclimatisation?
The pulmonary vascular resistance will fall
increased NO production
What is acute mountain sickness? AMS
Ascent to hgih altitude is too rapid - first sign taht something is wrong
HACE vs HAPE
HACE - high altitude cerebral edema - neurological condition
HAPE - hgih altitude pulmonary edema - pulmonar condition
SYmtoms of AMS x5
Headache - essential for diagnosis Poor sleep Tiredness Loss of appetite, nausea, vomiting Dizziness
Think alcohol hangover
How are the symptoms of AMS scored?
Each symptoms is scored 0-3 for severity and >3 is diagnosis fo AMS
At what height will everyone suffer from AMS?
5000m
What si teh treatmetn for mild AMS?
rest and no further ascent
hat is the treatmetn for severe AMS? x4
Descent
Oxygen
Acetaxolamide
Dexamethasone
What is acetaxolamide?
Carbonic anhydrase inhibitor
Function of carbonic anhydrase?
Renal reabsorption of bicarbonate
Location of carbonic anhydrase?
Proximal convoluted tubule
Normally - how much bicarbonate is reabsorbed?
All of it
